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Title:
Purification and composition of Ca2+/Mg2+ ATPase from rat heart plasma membrane
Abstract:
The Ca2+/Mg2+ ATPase, which is activated by millimolar concentrations of Ca2+ or Mg2+, was solubilized from rat heart plasma membrane by employing lysophosphatidylcholine, CHAPS, NaI, EDTA and Tris-HCl at pH 7.4.
The enzyme was purified by sucrose density gradient, Affi-Gel Blue column and Sepharose 6B column chromatography.
The purified enzyme was seen as a single peptide band in the sodium dodecyl sulfate polyacrylamide gel electrophoresis with a molecular weight of about 90,000.
The apparent molecular weight of the holoenzyme as determined under non-dissociating conditions by gel filtration on Sepharose 6B column was about 180,000 indicating two subunits.
The enzyme was insensitive to ouabain, verapamil, vanadate, oligomycin, N,N-dicyclohexylcarbodiimide and NaN3, but was markedly inhibited by 20 microM gramicidin S and 50 microM trifluoperazine.
Analysis of the purified Ca2+/Mg2+ ATPase revealed the presence of 17 amino acids where leucine, glutamic acid and aspartic acid were the major components and histidine, cysteine and methionine were the minor components.
The purified enzyme was associated with 19.7 mumol phospholipid/mg protein which was 60 times higher than the phospholipid content in plasma membrane.
The cholesterol content in the purified enzyme preparation was 0.75 mumol/mg protein and this represented an 8-fold enrichment over plasma membrane.
The glycoprotein nature of the enzyme was evident from the positive periodic acid-Schiff staining of the purified Ca2+/Mg2+ ATPase in the sodium dodecyl sulfate polyacrylamide gel.
The polysaccharide content of the enzyme was enriched 8-fold over plasma membrane; neuraminidase treatment decreased the polysaccharide content.
Concanavalin A prevented the ATP-dependent inactivation of the purified Ca2+/Mg2+ ATPase and was found to bind to the purified enzyme with a KD of 576 nM and Bmax of 4.52 nmol/mg protein.
The results indicate that Ca2+/Mg2+ ATPase is a glycoprotein and contains a large amount of lipids. | 13,015 |
Title:
Oligoribonuclease is the primary degradative enzyme for pGpG in Pseudomonas aeruginosa that is required for cyclic-di-GMP turnover
Abstract:
The bacterial second messenger cyclic di-GMP (c-di-GMP) controls biofilm formation and other phenotypes relevant to pathogenesis.
Cyclic-di-GMP is synthesized by diguanylate cyclases (DGCs).
Phosphodiesterases (PDE-As) end signaling by linearizing c-di-GMP to 5ʹ-phosphoguanylyl-(3ʹ,5ʹ)-guanosine (pGpG), which is then hydrolyzed to two GMP molecules by yet unidentified enzymes termed PDE-Bs.
We show that pGpG inhibits a PDE-A from Pseudomonas aeruginosa.
In a dual DGC and PDE-A reaction, excess pGpG extends the half-life of c-di-GMP, indicating that removal of pGpG is critical for c-di-GMP homeostasis.
Thus, we sought to identify the PDE-B enzyme(s) responsible for pGpG degradation.
A differential radial capillary action of ligand assay-based screen for pGpG binding proteins identified oligoribonuclease (Orn), an exoribonuclease that hydrolyzes two- to five-nucleotide-long RNAs.
Purified Orn rapidly converts pGpG into GMP.
To determine whether Orn is the primary enzyme responsible for degrading pGpG, we assayed cell lysates of WT and ∆orn strains of P. aeruginosa PA14 for pGpG stability.
The lysates from ∆orn showed 25-fold decrease in pGpG hydrolysis.
Complementation with WT, but not active site mutants, restored hydrolysis.
Accumulation of pGpG in the ∆orn strain could inhibit PDE-As, increasing c-di-GMP concentration.
In support, we observed increased transcription from the c-di-GMP–regulated pel promoter.
Additionally, the c-di-GMP–governed auto-aggregation and biofilm phenotypes were elevated in the ∆orn strain in a pel-dependent manner.
Finally, we directly detect elevated pGpG and c-di-GMP in the ∆orn strain.
Thus, we identified that Orn serves as the primary PDE-B enzyme that removes pGpG, which is necessary to complete the final step in the c-di-GMP degradation pathway. | 13,036 |
Title:
Developing a therapeutic relationship with a blind client with a severe intellectual disability and persistent challenging behaviour
Abstract:
Purpose.
A blind, severely intellectually impaired boy aged 17 with Down syndrome and persistent serious challenging behavior received attachment-based behavior modification treatment.
The aim was to study the effect of the treatment and the development of the therapeutic attachment relationship.
Method.
In a single-case study, attachment therapy sessions alternated with control sessions.
Treatment started with attachment therapy (phase 1), followed by behavior modification (phase 2).
The instruments used were: Residential observation lists for challenging behavior, video analyses of attachment behavior in therapy sessions and physiological indicators of affect regulation measuring the pre-ejection period (PEP) and respiratory sinus arrhythmia (RSA) as indices of cardiac sympatho-vagal activity.
Results.
The client exhibited less frequent and less intensely challenging behavior.
The data indicated more appropriate replacement behavior and less PEP arousal during the behavior modification treatment given by the attachment therapist compared to the control therapist who used the same protocol.
The client showed more active and longer-lasting attachment behavior, especially proximity seeking, towards the attachment therapist than towards the control therapist.
Conclusions.
Attachment-based psychotherapy proved successful in eliciting attachment behavior in a severely intellectually disabled, socially deprived, behaviorally and affectively dysregulated adolescent.
The resulting relationship proved to be a therapeutic platform conducive to behavior change. | 13,099 |
Title:
hTID-1 defines a novel regulator of c-Met Receptor signaling in renal cell carcinomas
Abstract:
The c-Met receptor tyrosine kinase (MetR) is frequently overexpressed and constitutively phosphorylated in a number of human malignancies.
Activation of the receptor by its ligand, hepatocyte growth factor (HGF), leads to increased cell proliferation, motility, survival and disruption of adherens junctions.
In this study, we show that hTid-1, a DNAJ/Hsp40 chaperone, represents a novel modulator of the MetR signaling pathway.
hTid-1 is a co-chaperone of the Hsp70 family of proteins, and has been shown to regulate a number of cellular signaling proteins including several involved in tumorigenic and apoptotic pathways.
In this study we demonstrate that hTid-1 binds to unphosphorylated MetR and becomes dissociated from the receptor upon HGF stimulation.
Overexpression of the short form of hTid-1 (hTid-1S) in 786-0 renal clear cell carcinomas (RCCs) enhances MetR kinase activity leading to an increase in HGF-mediated cell migration with no discernible effect on cell proliferation.
By contrast, knockdown of hTid-1 markedly impairs both the onset and amplitude of MetR phosphorylation in response to HGF without altering receptor protein levels.
hTid-1-depleted cells display defective migratory properties, coincident with inhibition of ERK/MAP kinase and STAT3 pathways.
Taken together, our findings denote hTid-1S as an essential regulatory component of MetR signaling.
We propose that the binding of hTid-1S to MetR may stabilize the receptor in a ligand-competent state and this stabilizing function may influence conformational changes that take place during the catalytic cycle that promote kinase activation.
Given the prevalence of HGF/MetR pathway activation in human cancers, targeted inhibition of hTid-1 may be a useful therapeutic in the management of MetR-dependent malignancies. | 13,156 |
Title:
Does habitat availability determine geographical-scale abundances of coral-dwelling fishes?
Abstract:
The role of local-scale processes in determining large-scale patterns of abundance is a key issue in ecology.
To test whether habitat use determines local and large-scale patterns of abundance of obligate coral-dwelling fishes (genus Gobiodon), the author compared habitat availability with the abundance of four species, G. axillaris, G. brochus, G. histrio, and G. quinquestrigatus, among four locations, from the southern Great Barrier Reef to northern Papua New Guinea.
Habitat availability, measured at tens of meters, explained 47–65% of the variation in abundance of these species among geographic locations spanning over 2,000 km.
Therefore, local-scale patterns of habitat use appear to determine much larger-scale patterns of abundance in these habitat-specialist fish.
The abundances of all species, except G. brochus, were also closely associated with particular exposure regimes, independently of the abundance of corals.
Broad-scale habitat selection for reef types within locations can most easily explain this pattern.
The abundances of all species, except G. brochus, also varied among geographic locations, independently of coral abundances.
Therefore, the abundances of these species are influenced by either geographic variation in local-scale processes that was not measured, or additional processes acting at very large spatial scales. | 13,173 |
Title:
Efficient Non-Viral Ocular Gene Transfer with Compacted DNA Nanoparticles
Abstract:
Background ::: The eye is an excellent candidate for gene therapy as it is immune privileged and much of the disease-causing genetics are well understood.
Towards this goal, we evaluated the efficiency of compacted DNA nanoparticles as a system for non-viral gene transfer to ocular tissues.
The compacted DNA nanoparticles examined here have been shown to be safe and effective in a human clinical trial, have no theoretical limitation on plasmid size, do not provoke immune responses, and can be highly concentrated.
::: Methods and Findings ::: Here we show that these nanoparticles can be targeted to different tissues within the eye by varying the site of injection.
Almost all cell types of the eye were capable of transfection by the nanoparticle and produced robust levels of gene expression that were dose-dependent.
Most impressively, subretinal delivery of these nanoparticles transfected nearly all of the photoreceptor population and produced expression levels almost equal to that of rod opsin, the highest expressed gene in the retina. ::: Conclusions ::: As no deleterious effects on retinal function were observed, this treatment strategy appears to be clinically viable and provides a highly efficient non-viral technology to safely deliver and express nucleic acids in the retina and other ocular tissues. | 13,236 |
Title:
Renal Production, Uptake, and Handling of Circulating Klotho
Abstract:
αKlotho is a multifunctional protein highly expressed in the kidney.
Soluble αKlotho is released through cleavage of the extracellular domain from membrane αKlotho by secretases to function as an endocrine/paracrine substance.
The role of the kidney in circulating αKlotho production and handling is incompletely understood, however.
Here, we found higher αKlotho concentration in suprarenal compared with infrarenal inferior vena cava in both rats and humans.
In rats, serum αKlotho concentration dropped precipitously after bilateral nephrectomy or upon treatment with inhibitors of αKlotho extracellular domain shedding.
Furthermore, the serum half-life of exogenous αKlotho in anephric rats was four- to five-fold longer than that in normal rats, and exogenously injected labeled recombinant αKlotho was detected in the kidney and in urine of rats.
Both in vivo (micropuncture) and in vitro (proximal tubule cell line) studies showed that αKlotho traffics from the basal to the apical side of the proximal tubule via transcytosis.
Thus, we conclude that the kidney has dual roles in αKlotho homeostasis, producing and releasing αKlotho into the circulation and clearing αKlotho from the blood into the urinary lumen. | 13,238 |
Title:
Pharmacodynamics of vancomycin in elderly patients aged 75 years or older with methicillin-resistant Staphylococcus aureus hospital-acquired pneumonia
Abstract:
BACKGROUND ::: Methicillin-resistant Staphylococcus aureus (MRSA) infections are associated with significant mortality and health care costs.
To improve treatment outcomes for MRSA, a better understanding of the pharmacokinetic/pharmacodynamic parameters of vancomycin is required to develop optimal dosing strategies, particularly in elderly patients (≥75 years of age) with limited renal function.
The purpose of this study was to determine whether pharmacokinetic indices for vancomycin are associated with mortality from MRSA hospital-acquired pneumonia in elderly patients.
::: ::: ::: METHODS ::: We conducted a retrospective observational study with 28-day mortality as the primary outcome for 94 patients with MRSA hospital-acquired pneumonia who had been treated with vancomycin from January 2006 through December 2012.
Our most recent sampling of MRSA isolates had a minimum inhibitory concentration (MIC) for vancomycin of 1 μg/mL (86%), indicating that the area under the curve (AUC) was equal to the AUC/MIC in these isolates.
The primary data from 28-day survivors and nonsurvivors were compared. ::: ::: ::: RESULTS ::: Among 94 elderly patients, the mean age was 82 (75-99) years.
Multivariate analyses revealed that, among the factors examined, only the nonoptimal AUC (<250, >450 μg*h/mL) was an independent predictor of 28-day mortality in elderly patients (odds ratio 23.156, 95% confidence interval 6.814-78.687, P < 0.001).
We detected a significant difference for increasing nephrotoxicity in nonsurvivors (nine of 32 patients [28%]) compared with survivors (three of 62 patients [4.8%], P = 0.003). ::: ::: ::: CONCLUSION ::: This finding indicates that patients with potentially poor renal function are likely to have increased AUC values and a poor prognosis.
Consideration of the pharmacokinetics/pharmacodynamics of vancomycin and targeting an AUC/MIC value of 250-450 μg*h/mL may result in improved treatment outcomes for elderly patients with MRSA hospital-acquired pneumonia. | 13,239 |
Title:
Transjugular intrahepatic portosystemic shunt in an infant
Abstract:
A 15-month-old girl, who presented with biliary cirrhosis secondary to cystic fibrosis with refractory ascites and recurrent intestinal bleeding, underwent percutaneous transjugular intrahepatic portosystemic shunting.
Immediately following the procedure the ascites disappeared and no further bleeding occurred.
The stent shunt was patent on Doppler ultrasound until the 22nd day.
The patient died on day 22 because of liver failure due to a low-flow syndrome with severe hepatic ischaemia, but with no recurrence of bleeding or ascites. | 13,243 |
Title:
Moderate tidal volumes and oxygen exposure during initiation of ventilation in preterm fetal sheep
Abstract:
BACKGROUND ::: Preterm infants often receive mechanical ventilation and oxygen at birth.
Exposure to large tidal volumes (V(T)s) at birth causes lung inflammation, and oxygen may amplify the injury.
We hypothesized that normal V(T) ventilation at birth causes lung injury that is exacerbated by 95% oxygen. ::: ::: ::: METHODS ::: The head and chest of anesthetized preterm fetal sheep (129 ± 1 d gestation) were surgically exteriorized while maintaining the placental circulation.
Fetuses were randomized to four groups with either V(T) ventilation to 6 ml/kg or continuous positive airway pressure of 5 cm H2O, and either 95%O2/5%CO2 or 95%N2/5%CO2.
Age-matched fetuses were used as controls.
After a 15-min intervention, the fetal lamb was returned to the uterus for 1 h 45 min. ::: ::: ::: RESULTS ::: In ventilated lambs, V(T) was 6.2 ± 0.4 ml/kg at 15 min.
Ventilation increased proinflammatory cytokines as compared with controls and lambs on continuous positive airway pressure, with recruitment of primarily monocytes to bronchoalveolar lavage fluid.
Early response protein 1 was activated around the bronchioles in V(T)-ventilated animals.
The 15-min oxygen exposure did not change inflammatory mediators or other markers of lung and oxidative stress. ::: ::: ::: CONCLUSION ::: A V(T) of 6-7 ml/kg at birth increased early markers of injury and lung inflammation.
Brief exposure to 95% oxygen did not alter lung inflammation. | 13,275 |
Title:
Impact of sleep‐related symptoms on clinical motor subtypes and disability in Parkinson's disease: a multicentre cross‐sectional study
Abstract:
Objectives To investigate the impact of sleep disturbances on Parkinson’s disease (PD) clinical motor subtypes and disease-related disability in a multicentre setting.
Methods We report a cross-sectional relationship between sleep-related symptoms and clinical motor subtypes (tremor dominant (TD); intermediate; postural instability and gait disturbances (PIGDs)) identified in a multicentre study, including 436 patients with PD and 401 age-matched controls.
PD-related sleep problems (PD-SP), excessive daytime sleepiness (EDS) and probable REM sleep behaviour disorder (pRBD) were evaluated using the PD sleep scale (PDSS)-2, Epworth Sleepiness Scale (ESS) and RBD screening questionnaire-Japanese version (RBDSQ-J), respectively.
Results PD-SP (PDSS-2 ≥18; 35.1% vs 7.0%), EDS (ESS ≥10; 37.8% vs 15.5%) and pRBD (RBDSQ-J ≥5; 35.1% vs 7.7%) were more common in patients with PD than in controls.
The prevalence of restless legs syndrome did not differ between patients with PD and controls (3.4% vs 2.7%).
After adjusting for age, sex, disease duration and Movement Disorder Society-Unified PD Rating Scale (MDS-UPDRS) part III score, the PIGD group had higher PDSS-2 and ESS scores than the TD group.
The RBDSQ-J scores did not differ among the TD, intermediate and PIGD groups.
A stepwise regression model predicting the MDS-UPDRS part II score identified the Hoehn and Yahr stage, followed by the number of sleep-related symptoms (PD-SP, EDS and pRBD), disease duration, MDS-UPDRS part III score, PIGD subtype, depression and MDS-UPDRS part IV score as significant predictors.
Conclusion Our study found a significant relationship between sleep disturbances and clinical motor subtypes.
An increased number of sleep-related symptoms had an impact on disease-related disability. | 13,299 |
Title:
Effect of Polygodial on the Mitochondrial ATPase of Saccharomyces cerevisiae
Abstract:
The fungicidal mechanism of a naturally occurring sesquiterpene dialdehyde, polygodial, was investigated in Saccharomyces cerevisiae.
In an acidification assay, polygodial completely suppressed the glucose-induced decrease in external pH at 3.13 μg/ml, the same as the fungicidal concentration.
Acidification occurs primarily through the proton-pumping action of the plasma membrane ATPase, Pma1p.
Surprisingly, this ATPase was not directly inhibited by polygodial.
In contrast, the two other membrane-bound ATPases in yeast were found to be susceptible to the compound.
The mitochondrial ATPase was inhibited by polygodial in a dose-dependent manner at concentrations similar to the fungicidal concentration, whereas the vacuolar ATPase was only slightly inhibited.
Cytoplasmic petite mutants, which lack mitochondrial DNA and are respiration deficient, were significantly less susceptible to polygodial than the wild type, as was shown in time-kill curves.
A pet9 mutant which lacks a functional ADP-ATP translocator and is therefore respiration dependent was rapidly inhibited by polygodial.
The results of these susceptibility assays link enzyme inhibition to physiological effect.
Previous studies have reported that plasma membrane disruption is the mechanism of polygodial-induced cell death; however, these results support a more complex picture of its effect.
A major target of polygodial in yeast is mitochondrial ATP synthase.
Reduction of the ATP supply leads to a suppression of Pma1 ATPase activity and impairs adaptive responses to other facets of polygodial's cellular inhibition. | 13,307 |
Title:
Using a model-based framework for analysing genetic diversity during germination and heterotrophic growth of Medicago truncatula
Abstract:
BACKGROUND AND AIMS ::: The framework provided by an emergence model was used: (1) for phenotyping germination and heterotrophic growth of Medicago truncatula in relation to two major environmental factors, temperature and water potential; and (2) to evaluate the extent of genetic differences in emergence-model parameters. ::: ::: ::: METHODS ::: Eight cultivars and natural accessions of M. trunculata were studied.
Germination was recorded from 5 to 30 degrees C and from 0 to -0.75 MPa, and seedling growth from 10 to 20 degrees C. ::: ::: ::: KEY RESULTS ::: Thermal time to reach 50 % germination was very short (15 degrees Cd) and almost stable between genotypes, while base temperature (2-3 degrees C) and base water potential for germination (-0.7 to -1.3 MPa) varied between genotypes.
Only 35 degrees Cd after germination were required to reach 30 mm hypocotyl length with significant differences among genotypes.
Base temperature for elongation varied from 5.5 to 7.5 degrees C. Low temperatures induced a general shortening of the seedling, with some genotypes more responsive than others.
No relationship with initial seed mass or seed reserve distribution was observed, which might have explained differences between genotypes and the effects of low temperatures. ::: ::: ::: CONCLUSIONS ::: The study provides a set of reference values for M. trunculata users.
The use of the ecophysiological model allows comparison of these values between such non-crop species and other crops.
It has enabled phenotypic variability in response to environmental conditions related to the emergence process to be identified.
The model will allow simulation of emergence differences between genotypes in a range of environments using these parameter values.
Genomic tools available for the model species M. trunculata will make it possible to analyse the genetic and molecular determinants of these differences. | 13,529 |
Title:
Pain Relief as a Primary Treatment Goal: at What Point does Functioning and Well-Being Become more Important? a Case Study of an Adolescent with Debilitating Chronic Pain
Abstract:
BACKGROUND: Pediatric chronic pain is a common problem with significant economic implications and devastating consequences on quality of life.
The present report describes a case involving a 15-year-old girl with severe and debilitating chronic pain. | 13,549 |
Title:
Substance P excites GABAergic neurons in the mouse central amygdala through neurokinin 1 receptor activation
Abstract:
Substance P (SP) is implicated in stress regulation and affective and anxiety-related behavior.
Particularly high expression has been found in the main output region of the amygdala complex, the central amygdala (CE).
Here we investigated the cellular mechanisms of SP in CE in vitro, taking advantage of glutamic acid decarboxylase-green fluorescent protein (GAD67-GFP) knockin mice that yield a reliable labeling of GABAergic neurons, which comprise 95% of the neuronal population in the lateral section of CE (CEl).
In GFP-positive neurons within CEl, SP caused a membrane depolarization and increase in input resistance, associated with an increase in action potential firing frequency.
Under voltage-clamp conditions, the SP-specific membrane current reversed at −101.5 ± 2.8 mV and displayed inwardly rectifying properties indicative of a membrane K+ conductance.
Moreover, SP responses were blocked by the neurokinin type 1 receptor (NK1R) antagonist L-822429 and mimicked by the NK1R agonist [Sar9,Met(O2)11]-SP.... | 13,560 |
Title:
Faster and More Accurate Sequence Alignment with SNAP
Abstract:
We present the Scalable Nucleotide Alignment Program (SNAP), a new short and long read aligner that is both more accurate (i.e., aligns more reads with fewer errors) and 10-100x faster than state-of-the-art tools such as BWA.
Unlike recent aligners based on the Burrows-Wheeler transform, SNAP uses a simple hash index of short seed sequences from the genome, similar to BLAST's.
However, SNAP greatly reduces the number and cost of local alignment checks performed through several measures: it uses longer seeds to reduce the false positive locations considered, leverages larger memory capacities to speed index lookup, and excludes most candidate locations without fully computing their edit distance to the read.
The result is an algorithm that scales well for reads from one hundred to thousands of bases long and provides a rich error model that can match classes of mutations (e.g., longer indels) that today's fast aligners ignore.
We calculate that SNAP can align a dataset with 30x coverage of a human genome in less than an hour for a cost of $2 on Amazon EC2, with higher accuracy than BWA.
Finally, we describe ongoing work to further improve SNAP. | 13,601 |
Title:
Bexarotene Induces Cellular Senescence in MMTV-Neu Mouse Model of Mammary Carcinogenesis
Abstract:
Previous studies have shown that retinoids and rexinoids can prevent breast cancer in animal models and in women with increased risk of developing the disease.
The cellular effects of these vitamin A analogues have been primarily associated with induction of differentiation and inhibition of proliferation.
In this study, we tested the hypothesis that bexarotene (LGD1069, Targretin), a rexinoid, can not only inhibit cell proliferation but also induce cellular senescence in mammary epithelial cells, premalignant lesions, and tumors of the MMTV-Neu model of mammary carcinogenesis, which develops estrogen receptor-negative tumors.
Mice with palpable mammary tumors were treated for 4 weeks with bexarotene at 80 or 40 mg/kg body weight, and senescent cells were determined by SA-β-Gal assay.
Bexarotene decreased in a dose-dependent manner the multiplicity of premalignant lesions and tumors, and this was associated with inhibition of cell proliferation and induction of cellular senescence and apoptosis.
By double labeling of senescent cells, first by SA-β-Gal and then by antibodies against genes related to cellular senescence, we found that p21, p16, and RARβ, but not p53, were upregulated by bexarotene in mammary tumors and in breast cancer cell lines, suggesting involvement of multiple signaling pathways in mediating the senescence program of rexinoids.
These findings indicate that, in addition to cell proliferation and apoptosis, cellular senescence could be used as a potential biomarker of response in breast cancer prevention and therapy studies with rexinoids and possibly with other antitumor agents. | 13,623 |
Title:
Selective inhibition of mesophyll chloroplast development in some C4-pathway species by low night temperature
Abstract:
SummaryExposure of plants of Sorghum bicolor L. line E 1287 and hybrid NK 145, of Digitaria smutsii Stapf, and of Paspalum dilatatum L.-grasses having the C4 pathway of photosynthesis-to temperatures of 4°, 2.5°, 2.5° and-3°, respectively, for a single night caused the formation within 36 h of transverse, irreversibly chlorotic bands on emerging leaves.
Chlorosis was associated with the presence of chlorophyll-deficient, structurally abnormal plastids in most mesophyll cells, whereas chloroplasts in adjacent bundle-sheath cells were green and possessed a normal lamellar structure.
The ultrastructure of other organelles in the chlorotic mesophyll cells appeared normal and the levels of cytoplasmic rRNA, non-plastid lipids and isocitrate dehydrogenase were similar or slightly higher in chlorotic compared with green lamina.
The content of chloroplast rRNA and plastid lipids in the chlorotic tissue was low.
Activities of all C4-pathway enzymes examined were lower in the chlorotic tissue but phosphopyruvate carboxylase, NADP-malate dehydrogenase and adenylate kinase were reduced to a greater extent than ribulose diphosphate carboxylase, fructose diphosphate aldolase and malic enzyme.
The region of emerging leaves that contained mesophyll plastids susceptible to low temperature was identified and the stages of plastid ontogeny below, within and above this region examined.
During normal differentiation rapid increases in plastid size and in the content of chloroplast rRNA, chlorophyll, plastid lipids and in the activities of C4-pathway enzymes occur at a developmental stage subsequent to that at which plastids are susceptible to low temperature. | 13,634 |
Title:
Ranibizumab: A Review of its Use in Myopic Choroidal Neovascularization
Abstract:
Ranibizumab (Lucentis®) is the first inhibitor of vascular endothelial growth factor (VEGF)-A licensed for the treatment of visual impairment due to choroidal neovascularization (CNV) secondary to pathologic myopia (i.e. myopic CNV).
The drug inhibits biologically active isoforms of VEGF-A and is administered via intravitreal injection, with the number of treatments required depending on disease activity.
The clinical benefit of such a ranibizumab regimen in adults with myopic CNV was demonstrated in a randomized, double-masked, active comparator-controlled, phase III trial known as RADIANCE.
In this trial, intravitreal ranibizumab was superior to the standard licensed therapy available to these patients thus far, namely intravenous verteporfin plus photodynamic therapy (verteporfin PDT), in improving visual acuity from month 1 through month 3 of treatment, with improvements in some aspects of vision-related function also evident with ranibizumab versus verteporfin PDT at 3 months.
Improvements in vision were sustained for up to 12 months in ranibizumab recipients and were mirrored by improvements in anatomic outcomes.
Few ranibizumab injections were required over the trial, with more than 60 % of patients not needing to receive the drug from month 6 to 11.
Ranibizumab was generally well tolerated in RADIANCE, with few patients experiencing serious ocular or non-ocular adverse events. | 13,635 |
Title:
Cytogenetic studies on wild house mice from Belgium
Abstract:
The present status of Robertsonian karyotype variation in populations of wild mice from Belgium is presented.
Two fusions, Rb(4.12)1Nam and Rb(5.10)3Nam, were identified in the central plain of this flat country.
Surrounding this region only mice with the usual 2n=40 karyotype occurred.
From the distribution pattern some possible relationships to other Rb populations from Europe are discussed. | 13,673 |
Title:
Isolation and characterization of seventy-nine full-length mariner-like transposase genes in the Bambusoideae subfamily
Abstract:
Mariner-like elements (MLEs) are the most diverse and widespread transposable elements, with members of the MLE superfamily found in fungi, plants, ciliates and animals.
In a previous study, we characterized 82 MLE transposase gene fragments (average length 383 bp) in 44 bamboo species, indicating that MLEs are widespread, abundant and diverse in the Bambusoideae subfamily.
In this study, we isolated 79 full-length MLE transposase genes from 63 bamboo species representing 38 genera in six subtribes mainly found in China.
The transposases were highly conserved, mostly uniform in length and contained intact DNA-binding motifs and DD39D catalytic domains with few notable frameshift, indel and nonsense mutations.
This suggested the MLEs are probably still mobile, not yet affected by vertical inactivation.
A phylogenetic tree of the Bambusoideae subfamily established using ribosomal DNA internal transcribed spacer sequences was incongruent with a second tree based on the MLE transposase genes.
This evidence, together with the presence of near-identical MLEs in distantly related species and diverse MLEs in closely related species, indicates that MLEs have evolved in a distinct manner, probably independently of speciation events in the subfamily.
The evolution and diversity of MLE transposase genes in the Bambusoideae subfamily is discussed. | 13,703 |
Title:
Six-Month Angiographic Outcome After Successful Repeat Percutaneous Intervention for In-Stent Restenosis
Abstract:
Background—In-stent restenosis is an increasing clinical problem.
Discordant results have been published regarding the risk of recurrent restenosis after repeat angioplasty for the treatment of in-stent restenosis.
Methods and Results—One hundred three consecutive patients (107 vessels) underwent repeat percutaneous intervention for the treatment of in-stent restenosis and were entered in a prospective angiographic follow-up program.
Repeat balloon angioplasty was performed at 93 lesions (87%) and additional stenting at 14 lesions (13%).
The primary success rate was 98%.
Six-month angiographic follow-up was performed in 85% of eligible patients.
Restenosis was determined by quantitative angiography.
Restenosis defined as a >50% diameter stenosis at follow-up was observed at 22% of lesions.
The rate of target-lesion revascularization at 6 months was 17%.
Repeat intervention for diffuse in-stent restenosis and severe stenosis before repeat intervention were associated with significantly higher rates of recu... | 13,798 |
Title:
Cancer surveillance in ulcerative colitis and Crohn's disease: new strategies.
Abstract:
PURPOSE OF REVIEW ::: Inflammatory bowel disease (IBD) patients have a higher incidence of colon cancer than the general population.
Colon cancer surveillance has traditionally involved taking numerous random biopsies to provide sufficient yield to detect dysplasia.
Recently, consensus guidelines have been published which promote the use of chromoendoscopy for IBD colon cancer surveillance.
This presents a new set of opportunities and challenges in the evaluation and management of dysplasia in IBD. ::: ::: ::: RECENT FINDINGS ::: Dysplasia, previously thought to be 'invisible' to the endoscopist, is now considered to be 'visible' in the majority of cases with the advent of the use of high-definition endoscopy and chromoendoscopy.
This changes how we manage dysplastic lesions, providing the patient options for endoscopic resection rather than promoting total proctocolectomy. ::: ::: ::: SUMMARY ::: Implemention of chromoendoscopy may require additional training for endoscopists unfamiliar with the technique.
However, if this proves to be cost-effective and provides a higher sensitivity in dysplasia detection, then widespread education and implementation will be well worth the efforts.
To do so, future studies will need to prove its benefits in preventing or reducing colon cancer morbidity and mortality in this high-risk patient population. | 13,832 |
Title:
Quantitative genomics of locomotor behavior in Drosophila melanogaster
Abstract:
BackgroundLocomotion is an integral component of most animal behaviors, and many human health problems are associated with locomotor deficits.
Locomotor behavior is a complex trait, with population variation attributable to many interacting loci with small effects that are sensitive to environmental conditions.
However, the genetic basis of this complex behavior is largely uncharacterized.
ResultsWe quantified locomotor behavior of Drosophila melanogaster in a large population of inbred lines derived from a single natural population, and derived replicated selection lines with different levels of locomotion.
Estimates of broad-sense and narrow-sense heritabilities were 0.52 and 0.16, respectively, indicating substantial non-additive genetic variance for locomotor behavior.
We used whole genome expression analysis to identify 1,790 probe sets with different expression levels between the selection lines when pooled across replicates, at a false discovery rate of 0.001.
The transcriptional responses to selection for locomotor, aggressive and mating behavior from the same base population were highly overlapping, but the magnitude of the expression differences between selection lines for increased and decreased levels of behavior was uncorrelated.
We assessed the locomotor behavior of ten mutations in candidate genes with altered transcript abundance between selection lines, and identified seven novel genes affecting this trait.
ConclusionExpression profiling of genetically divergent lines is an effective strategy for identifying genes affecting complex behaviors, and reveals that a large number of pleiotropic genes exhibit correlated transcriptional responses to multiple behaviors. | 13,871 |
Title:
Bacterial, Archaeal, and Eukaryotic Diversity across Distinct Microhabitats in an Acid Mine Drainage
Abstract:
Acid mine drainages are characterized by their low pH and the presence of dissolved toxic metallic species.
Microorganisms survive in different microhabitats within the ecosystem, namely water, sediments, and biofilms.
In this report, we surveyed the microbial diversity within all domains of life in the different microhabitats at Los Rueldos abandoned mercury underground mine (NW Spain), and predicted bacterial function based on community composition.
Sediment samples contained higher proportions of soil bacteria (AD3, Acidobacteria), as well as Crenarchaeota and Methanomassiliicoccaceae archaea.
Oxic and hypoxic biofilm samples were enriched in bacterial iron oxidizers from the genus Leptospirillum, order Acidithiobacillales, class Betaproteobacteria, and archaea from the class Thermoplasmata.
Water samples were enriched in Cyanobacteria and Thermoplasmata archaea at a 3-98% of the sunlight influence, whilst Betaproteobacteria, Thermoplasmata archaea, and Micrarchaea dominated in acid water collected in total darkness.
Stalactites hanging from the Fe-rich mine ceiling were dominated by the neutrophilic iron oxidizer Gallionella and other lineages that were absent in the rest of the microhabitats (e.g., Chlorobi, Chloroflexi).
Eukaryotes were detected in biofilms and open-air water samples, and belonged mainly to clades SAR (Alveolata and Stramenopiles), and Opisthokonta (Fungi).
Oxic and hypoxic biofilms displayed higher proportions of ciliates (Gonostomum, Oxytricha), whereas water samples were enriched in fungi (Paramicrosporidium and unknown microbial Helotiales).
Predicted function through bacterial community composition suggested adaptive evolutive convergence of function in heterogeneous communities.
Our study showcases a broad description of the microbial diversity across different microhabitats in the same environment and expands the knowledge on the diversity of microbial eukaryotes in AMD habitats. | 13,904 |
Title:
Self-reported sitting time is not associated with incidence of cardiovascular disease in a population-based cohort of mid-aged women
Abstract:
In Westernised societies adults are increasingly spending many hours each day in sedentary, low energy expenditure activities such as sitting.
Although there is growing evidence on the relationship between television/screen time and increased cardiovascular disease mortality, very little is known about the association between total sitting time (in different domains) and cardiovascular disease incidence.
We investigated this in a population-based cohort of mid-aged women in Australia.
Data were from 6154 participants in the 1946–51 birth cohort of the Australian Longitudinal Study on Women’s Health who were free of cardiovascular disease at baseline.
Survival analysis was used to determine the association between self-reported sitting time and cardiovascular disease incidence, determined through hospital diagnoses and cause of death data.
During a mean (± SD) follow-up time of 9.9 ± 1.2 years, 177 cases of cardiovascular disease occurred.
Mean sitting time (± SD) was 5.4 ± 2.6 hours a day.
Sitting time was not associated with incident cardiovascular disease (adjusted hazard ratio 0.97, 95% CI 0.92 to 1.03).
We found no interaction between physical activity and sitting time and cardiovascular disease.
In mid-aged women sitting time does not appear to be associated with cardiovascular disease incidence.
These findings are contrary to expectations, given the growing evidence of a relationship between sitting time and cardiovascular disease mortality.
Research in this area is scarce and additional studies are needed to confirm or refute these findings. | 13,947 |
Title:
Dynamics of phosphodiester synthesis by DNA ligase
Abstract:
Ligases are essential actors in DNA replication, recombination, and repair by virtue of their ability to seal breaks in the phosphodiester backbone.
Ligation proceeds through a nicked DNA-adenylate intermediate (AppDNA), which must be sealed quickly to avoid creating a potentially toxic lesion.
Here, we take advantage of ligase-catalyzed AMP-dependent incision of a single supercoiled DNA molecule to observe the step of phosphodiester synthesis in real time.
An exponentially distributed number of supercoils was relaxed per successful incision-resealing event, from which we deduce the torque-dependent ligation probability per DNA swivel.
Premature dissociation of ligase from nicked DNA-adenylate accounted for approximately 10% of the observed events.
The ability of ligase to form a C-shaped protein clamp around DNA is a key determinant of ligation probability per turn and the stability of the ligase-AppDNA intermediate.
The estimated rate of phosphodiester synthesis by DNA ligase (400 s(-1)) is similar to the high rates of phosphodiester synthesis by replicative DNA polymerases. | 13,968 |
Title:
Neuroendocrine Control of Body Fluid Metabolism
Abstract:
Mammals control the volume and osmolality of their body fluids from stimuli that arise from both the intracellular and extracellular fluid compartments.
These stimuli are sensed by two kinds of receptors: osmoreceptor-Na+ receptors and volume or pressure receptors.
This information is conveyed to specific areas of the central nervous system responsible for an integrated response, which depends on the integrity of the anteroventral region of the third ventricle, e.g., organum vasculosum of the lamina terminalis, median preoptic nucleus, and subfornical organ.
The hypothalamo-neurohypophysial system plays a fundamental role in the maintenance of body fluid homeostasis by secreting vasopressin and oxytocin in response to osmotic and nonosmotic stimuli.
Since the discovery of the atrial natriuretic peptide (ANP), a large number of publications have demonstrated that this peptide provides a potent defense mechanism against volume overload in mammals, including humans.
ANP is mostly localized in the heart, but ANP and its receptor are also found in hypothalamic and brain stem areas involved in body fluid volume and blood pressure regulation.
Blood volume expansion acts not only directly on the heart, by stretch of atrial myocytes to increase the release of ANP, but also on the brain ANPergic neurons through afferent inputs from baroreceptors.
Angiotensin II also plays an important role in the regulation of body fluids, being a potent inducer of thirst and, in general, antagonizes the actions of ANP.
This review emphasizes the role played by brain ANP and its interaction with neurohypophysial hormones in the control of body fluid homeostasis. | 14,046 |
Title:
Biofeedback-based cognitive-behavioral treatment compared with occlusal splint for temporomandibular disorder: a randomized controlled trial.
Abstract:
OBJECTIVES ::: Cognitive-behavioral treatment has proven efficacy for chronic temporomandibular disorder (TMD).
However, most patients receive dental treatment that may not address psychological comorbidities often present in TMD.
The aim of the present study was to evaluate the efficacy of biofeedback-based cognitive-behavioral treatment (BFB-CBT) versus dental treatment with occlusal splint (OS).
Moreover, changes in nocturnal masseter muscle activity (NMMA) were investigated.
::: ::: ::: METHODS ::: Fifty-eight patients with chronic TMD were randomly assigned to receive either 8 weekly sessions of BFB-CBT or 8 weeks of OS treatment.
Diagnoses were established using Research Diagnostic Criteria for TMD.
Pain intensity and disability were defined as primary outcomes.
Secondary outcomes included emotional functioning, pain coping, somatoform symptoms, treatment satisfaction, and adverse events.
NMMA was assessed during 3 nights pretreatment and posttreatment with portable devices.
Follow-up assessment took place 6 months after the treatment. ::: ::: ::: RESULTS ::: Both treatments resulted in significant reductions in pain intensity and disability, with similar amounts of clinically meaningful improvement (45% for BFB-CBT and 48% for OS).
Patients receiving BFB-CBT showed significantly larger improvements in pain coping skills.
Satisfaction with treatment and ratings of improvement were higher for BFB-CBT.
Effects were stable over 6 months, and tended to be larger in the BFB-CBT group for all outcomes.
No significant changes were observed in NMMA.
::: ::: ::: DISCUSSION ::: The fact that BFB-CBT resulted in larger improvements in pain coping skills, and was well accepted by the patients, underlines the importance and feasibility of psychological treatments in the clinical management of TMD. | 14,147 |
Title:
Specific biochemical inactivation of oncogenic Ras proteins by nucleoside diphosphate kinase.
Abstract:
Activating mutations of Ras have been implicated in approximately 30% of human cancers.
In every case, the biochemical consequence of such mutations is to disrupt the GTPase activity of Ras and to render Ras resistant to the actions of GTPase activating proteins.
Consequently, oncogenic Ras mutants are "locked" in a GTP-bound active state.
We detected a potent activity in Escherichia coli extract that can efficiently convert mutationally activated GTP-bound Ras to the inactive GDP-bound form.
Purification of the protein responsible for this activity led to the identification of the enzyme nucleoside diphosphate kinase (Ndk).
The human orthologue of Ndk is the NM23 metastasis suppressor, which we found to exhibit a similar activity.
Purified Ndk effectively inactivates several of the oncogenic forms of Ras that are seen frequently in human cancers, including RasD12, the most commonly detected Ras mutation.
Significantly, Ndk does not detectably affect wild-type Ras or an activated form of the Ras-related Rho GTPase.
These results demonstrate that it is possible, through biochemical means, to specifically inactivate oncogenic Ras as a potential therapeutic approach to tumors that harbor Ras mutations.
Moreover, the results suggest that the loss of NM23 expression that is commonly observed during tumor progression could lead to increased potency of oncogenic Ras proteins. | 14,152 |
Title:
Overexpression of Tissue Inhibitor of Metalloproteinases-3 in Intestinal and Cutaneous Lesions of Graft-versus-Host Disease
Abstract:
Matrix metalloproteinases (MMPs) have been implicated in the pathobiology of various T-cell-mediated inflammatory disorders of the intestine and skin.
Their synthetic inhibitor has been shown to prevent lethal acute graft-versus-host disease in animal models.
We intended to determine the expression of MMPs 1, 3, 7, 9, 10, 12, and 19 and tissue inhibitors of metalloproteinases (TIMPs) 1 and 3 in intestinal and cutaneous lesions of patients suffering from graft-versus-host disease after bone marrow transplantation.
In situ hybridizations for MMPs 1, 3, 7, 10, and 12 as well as TIMPs 1 and 3 were performed using (35)S-labeled cRNA probes on intestinal (n = 13) and cutaneous specimens (n = 9) from patients with graft-versus-host disease.
Immunohistochemical stainings were carried out to localize MMP-9, MMP-19, TIMP-3, and TGF-beta1 proteins, and TUNEL staining, to detect apoptotic cells.
TIMP-3 mRNA and protein were detected in cutaneous lesions in areas with vacuolar degeneration of the basal epidermal layer in all skin samples, and they colocalized with apoptotic keratinocytes and partly with staining for TGF-beta.
None of the MMPs examined were overexpressed in skin lesions.
Signals for MMP-1 and MMP-3 mRNA was found in 10/13 and 5/13 intestinal biopsies, respectively.
In the gut, MMP-19-positive epithelial cells, particularly in the crypts, were found in 10/13 samples.
Expression of MMPs 7, 9, 10, and 12 was absent or very low.
TIMPs 1 and 3 were expressed by stromal cells in 12/13 and 10/13 gut samples, respectively.
Whereas TIMP-1 was expressed particularly by subepithelial cells where epithelium had shed away, TIMP-3 was detected in deeper areas.
We conclude that MMPs are differentially regulated in the skin and gut lesions of graft-versus-host disease.
In agreement with previous data on cancer cells, TIMP-3, induced by TGF-beta1, may contribute to the apoptosis of keratinocytes in cutaneous graft-versus-host disease lesions, leading to typical histopathological changes.
We also conclude that MMPs play a less important role as effector molecules in intestinal graft-versus-host disease than in celiac or inflammatory bowel disease. | 14,265 |
Title:
The Application of Transformational Leadership Theory to Parenting: Questionnaire Development and Implications for Adolescent Self- Regulatory Efficacy and Life Satisfaction
Abstract:
We draw upon transformational leadership theory to develop an instrument to measure transformational parenting for use with adolescents.
First, potential items were generated that were developmentally appropriate and evidence for content validity was provided through the use of focus groups with parents and adolescents.
We subsequently provide evidence for several aspects of construct validity of measures derived from the Transformational Parenting Questionnaire (TPQ).
Data were collected from 857 adolescents (Mage = 14.70 years), who rated the behaviors of their mothers and fathers.
The results provided support for a second-order measurement model of transformational parenting.
In addition, positive relationships between mothers’ and fathers’ transformational parenting behaviors, adolescents’ self-regulatory efficacy for physical activity and healthy eating, and life satisfaction were found.
The results of this research support the application of transformational leadership theory to parenting behaviors, as well as the construct validity of measures derived from the TPQ.
(AUTHORS' ABSTRACT) | 14,279 |
Title:
A Proteomic Approach for Plasma Biomarker Discovery with iTRAQ Labelling and OFFGEL Fractionation
Abstract:
Human blood plasma contains a plethora of proteins, encompassing not only proteins that have plasma-based functionalities, but also possibly every other form of low concentrated human proteins.
As it circulates through the tissues, the plasma picks up proteins that are released from their origin due to physiological events such as tissue remodeling and cell death.
Specific disease processes or tumors are often characterized by plasma “signatures,” which may become obvious via changes in the plasma proteome profile, for example, through over expression of proteins.
However, the wide dynamic range of proteins present in plasma makes their analysis very challenging, because high-abundance proteins tend to mask those of lower abundance.
In the present study, we used a strategy combining iTRAQ as a reagent which improved the peptide ionization and peptide OFFGEL fractionation that has already been shown, in our previous research, to improve the proteome coverage of cellular extracts.
Two prefractioning methods were compared: immunodepletion and a bead-based library of combinatorial hexapeptide technology.
Our data suggested that both methods were complementary, with regard to the number of identified proteins.
iTRAQ labelling, in association with OFFGEL fractionation, allowed more than 300 different proteins to be characterized from 400 μg of plasma proteins. | 14,306 |
Title:
Endothelial lipase genetic polymorphisms and the lipid-lowering response in patients with coronary artery disease on rosuvastatin
Abstract:
BACKGROUND ::: Endothelial lipase (EL) plays an important role in the regulation of lipid metabolism by reducing the high density lipoprotein cholesterol (HDL-C) levels and inducing the macrophages to take up native low density lipoprotein cholesterol (LDL-C).
Our purpose was to investigate the impact of EL genetic polymorphisms on the lipid-lowering effects of rosuvastatin in Chinese coronary artery disease (CAD) patients. ::: ::: ::: METHODS ::: One hundred twenty-one unrelated CAD patients, who underwent the treatment with rosuvastatin (10mg/day) for four to eight weeks, were enrolled in this study.
Before and after treatment, serum lipids levels were measured.
Genotypes of EL 2037T/C and 2237 G/A polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. ::: ::: ::: RESULTS ::: Patients with EL 2037C allele (CC + CT) had significantly lower LDL-C levels than those with TT genotype (CC + CT: 2.60 ± 0.74 mmol/l; TT: 2.90 ± 0.87 mmol/l; P = 0.047), before rosuvastatin treatment.
No significant differences between baseline lipid levels and the EL 2237G/A genotypes were observed.
After treatment with rosuvastatin, total cholesterol (TC), high triglyceride (TG) and LDL-C levels decreased from baseline, on average, by 23.09 % (4.59 ± 0.96 mmol/l to 3.47 ± 0.83 mmol/l), 6.36 % (2.01 ± 1.18 mmol/l to 1.68 ± 1.16 mmol/l), 32.48 % (2.77 ± 0.83 mmol/l to 1.79 ± 0.62 mmol/l), respectively (all P < 0.05) in all patients.
While changes in HDL-C levels did not reach statistical significance.
No significant effects of EL 2037T/C or 2237G/A polymorphism were observed on lipid-lowering effects of rosuvastatin. ::: ::: ::: CONCLUSIONS ::: EL 2037T/C and 2237 G/A polymorphisms might not affect the lipid-owing effects of rosuvastatin in Chinese CAD patients. | 14,326 |
Title:
Decoding of MSTd Population Activity Accounts for Variations in the Precision of Heading Perception
Abstract:
Humans and monkeys use both vestibular and visual motion (optic flow) cues to discriminate their direction of self-motion during navigation.
A striking property of heading perception from optic flow is that discrimination is most precise when subjects judge small variations in heading around straight ahead, whereas thresholds rise precipitously when subjects judge heading around an eccentric reference.
We show that vestibular heading discrimination thresholds in both humans and macaques also show a consistent, but modest, dependence on reference direction.
We used computational methods (Fisher information, maximum likelihood estimation, and population vector decoding) to show that population activity in area MSTd predicts the dependence of heading thresholds on reference eccentricity.
This dependence arises because the tuning functions for most neurons have a steep slope for directions near straight forward.
Our findings support the notion that population activity in extrastriate cortex limits the precision of both visual and vestibular heading perception. | 14,401 |
Title:
Genetic cryptic species as biological invaders: the case of a Lessepsian fish migrant, the hardyhead silverside Atherinomorus lacunosus
Abstract:
Marine cryptic species, taxa that are morphologically identical but genetically distinct, may be important and underestimated components of the ecosystem.
The understanding of several ecological interactions, such as marine bioinvasions, could be altered by the correct description of the bioinvaders.
Here, we have focused our study on the hardyhead silverside, Atherinomorus lacunosus, a Lessepsian migrant.
Lessepsian migrants are those species that are invading the Mediterranean from the Red Sea via the Suez Canal.
We PCR amplified and sequenced the mitochondrial control region from individuals collected from the Mediterranean and the northern and southern Red Sea.
We found that the two Red Sea populations are likely to correspond to two previously undescribed cryptic species.
We also found that the Mediterranean individuals group with the northern Red Sea species.
The Mediterranean population showed high levels of genetic diversity and did not share haplotypes with the northern Red Sea population.
Lessepsian invasion by A. lacunosus probably occurred repeatedly and is likely to still be occurring. | 14,486 |
Title:
Posterior Dynamic Stabilization as a Salvage Procedure for Lumbar Facet Degeneration Following Total Disc Arthroplasty: Case report
Abstract:
Following an L5–S1 SB Charite disc III implantation, a 37-year-old female patient developed intractable radicular pain in the left L5 distribution.
The patient underwent a minimally invasive foraminotomy, and her symptoms improved significantly.
However, following recurrence of radicular pain, she showed signs of an L5–S1 facet degeneration and recurrent nerve root compression from hypertrophied synovium.
A partial facetectomy was then performed to completely decompress the L5 root with supplemental posterior dynamic stabilization using a pedicle-based flexible titanium rod system.
To date, the patient remains free of symptoms.
Although posterolateral fusion would have been a viable option, the application of a posterior dynamic system permitted segmental motion preservation. | 14,527 |
Title:
Is sleep education an effective tool for sleep improvement and minimizing metabolic disturbance and obesity in adolescents?
Abstract:
The prevalence of childhood obesity has increased significantly in recent years.
Obesity is associated with a range of adverse physiological, psychological and social outcomes and places a huge economical burden on healthcare systems around the world.
Insufficient sleep duration is common in adolescents and exacerbated by contemporary lifestyles, but may be a contributor to obesity onset and metabolic disruption.
We briefly review the current evidence surrounding the associations between sleep and obesity as well as diabetes.
Sleep improvement programs have been suggested as a potential avenue to raise awareness of the importance of sleep and ultimately enhance sleep behaviors/routines.
A review of the current literature supporting the efficacy of such programs is tentative.
Furthermore, very few studies have investigated if sleep enhancement has downstream positive effects on metabolic function or body weight in adolescents.
We highlight biological and social factors that intensify sleep loss in adolescents and recommend that these be targeted components in future interventions aimed at improving adolescent sleep. | 14,582 |
Title:
Genomic Analysis of the BMP Family in Glioblastomas
Abstract:
Glioblastoma multiforme (GBM) is a grade IV glioma with a median survival of 15 months.
Recently, bone morphogenetic protein (BMP) signaling has been shown to promote survival in xenograft murine models.
To gain a better understanding of the role of BMP signaling in human GBMs, we examined the genomic alterations of 90 genes associated with BMP signaling in GBM patient samples.
We completed this analysis using publically available datasets compiled through The Cancer Genome Atlas and the Glioma Molecular Diagnostic Initiative.
Here we show how mRNA expression is altered in GBM samples and how that is associated with patient survival, highlighting both known and novel associations between BMP signaling and GBM biology. | 14,712 |
Title:
Characteristics of CDC group 3 and group 5 coryneform bacteria isolated from clinical specimens and assignment to the genus Dermabacter.
Abstract:
Over a 1-year period, 11 isolates (including 5 from blood cultures) of the recently described CDC group 3 and group 5 coryneform bacteria were derived from clinical specimens and compared with reference strains.
Biochemical characteristics indicated a very close relationship between CDC group 3 and group 5 coryneform bacteria.
The ability of CDC group 3 and the inability of CDC group 5 coryneform bacteria to ferment xylose were the only reactions that were different for the two taxa.
Chemotaxonomic features of the two groups included the presence of meso-diaminopimelic acid, a lack of mycolic acids, and the presence of predominantly branched cellular fatty acids, a combination found among gram-positive rods only in Brevibacterium spp.
, Brachybacterium faecium, and Dermabacter hominis.
16S rRNA gene sequence analysis revealed that CDC group 3 and group 5 coryneform bacteria are members of the genus Dermabacter, which to date has been isolated exclusively from human skin. | 14,719 |
Title:
Metastatic disease from uveal melanoma: treatment options and future prospects
Abstract:
Uveal melanoma represents ∼85% of all ocular melanomas and up to 50% of patients develop metastatic disease.
Metastases are most frequently localised to the liver and, as few patients are candidates for potentially curative surgery, this is associated with a poor prognosis.
There is currently little published evidence for the optimal management and treatment of metastatic uveal melanoma and the lack of effective therapies in this setting has led to the widespread use of systemic treatments for patients with cutaneous melanoma.
Uveal and cutaneous melanomas are intrinsically different diseases and so dedicated management strategies and therapies for uveal melanoma are much needed.
This review explores the biology of uveal melanoma and how this relates to ongoing trials of targeted therapies in the metastatic disease setting.
In addition, we consider the options to optimise patient management and care. | 14,752 |
Title:
A comparison of surveillance systems for the dengue vector Aedes aegypti in port of Spain, Trinidad
Abstract:
When the currently used larval surveillance system (visual inspection) for the dengue vector Aedes aegypti was compared with the surveillance for the presence of eggs by ovitrapping in Port of Spain, Trinidad, it was found that the latter (39.1 percent) was significantly more sensitive than the visual inspection system (10.1 percent).
At the same time, the presence of the nuisance mosquito Culex quinquefasciatus was detected in 38.4 percent of the households.
Both Ae.
aegypti and Cx.
quinquefasciatus showed preference for ovipositional attractants in ovitraps: hay infusion > yeast suspension > plain tap water.
Although all the socioeconomic and geographic areas produced both mosquito species in 1996, upper middle class (UMC) areas (8.6-43.4 percent), produced more Ae.
aegypti than did lower middle class (LMC) area 7.8-38.8 percent), which produced more than working class (WC) areas (3.9-29.9 percent).
For Cx.
quinquefasciatus, the order of production was reversed with WC areas (50.1 percent) > LMC areas (30.0 percent) > UMC areas (26.0 percent).
Change in vector surveillance strategies incorporating some ovitrapping and stratified sampling are recommended for Caribbean countries(AU) | 14,804 |
Title:
How Do Risk Factors Work Together? Mediators, Moderators, and Independent, Overlapping, and Proxy Risk Factors
Abstract:
OBJECTIVE: The authors developed a methodological basis for investigating how risk factors work together.
Better methods are needed for understanding the etiology of disorders, such as psychiatric syndromes, that presumably are the result of complex causal chains.
METHOD: Approaches from psychology, epidemiology, clinical trials, and basic sciences were synthesized.
RESULTS: The authors define conceptually and operationally five different clinically important ways in which two risk factors may work together to influence an outcome: as proxy, overlapping, and independent risk factors and as mediators and moderators.
CONCLUSIONS: Classifying putative risk factors into these qualitatively different types can help identify high-risk individuals in need of preventive interventions and can help inform the content of such interventions.
These methods may also help bridge the gaps between theory, the basic and clinical sciences, and clinical and policy applications and thus aid the search for early diagnoses and ... | 14,868 |
Title:
Association mapping and fine mapping with TreeLD
Abstract:
SUMMARY ::: The program package TreeLD implements a unified approach to association mapping and fine mapping of complex trait loci and a novel approach to visualizing association data, based on an inferred ancestry of the sample.
Fundamentally, the TreeLD approach is based on the idea that the evidence for association at a particular position is contained in the ancestral tree relating the sampled chromosomes at that position.
TreeLD provides an easy-to-use interface and can be applied to case-control, TDT trio and quantitative trait data. | 14,894 |
Title:
Social learning and evolution: the cultural intelligence hypothesis
Abstract:
If social learning is more efficient than independent individual exploration, animals should learn vital cultural skills exclusively, and routine skills faster, through social learning, provided they actually use social learning preferentially.
Animals with opportunities for social learning indeed do so.
Moreover, more frequent opportunities for social learning should boost an individual's repertoire of learned skills.
This prediction is confirmed by comparisons among wild great ape populations and by social deprivation and enculturation experiments.
These findings shaped the cultural intelligence hypothesis, which complements the traditional benefit hypotheses for the evolution of intelligence by specifying the conditions in which these benefits can be reaped.
The evolutionary version of the hypothesis argues that species with frequent opportunities for social learning should more readily respond to selection for a greater number of learned skills.
Because improved social learning also improves asocial learning, the hypothesis predicts a positive interspecific correlation between social-learning performance and individual learning ability.
Variation among primates supports this prediction.
The hypothesis also predicts that more heavily cultural species should be more intelligent.
Preliminary tests involving birds and mammals support this prediction too.
The cultural intelligence hypothesis can also account for the unusual cognitive abilities of humans, as well as our unique mechanisms of skill transfer. | 14,907 |
Title:
Functional redundancy and/or ongoing pseudogenization among F-box protein genes expressed in Arabidopsis male gametophyte
Abstract:
F-box protein genes family is one of the largest gene families in plants, with almost 700 predicted genes in the model plant Arabidopsis.
F-box proteins are key components of the ubiquitin proteasome system that allows targeted protein degradation.
Transcriptome analyses indicate that half of these F-box protein genes are found expressed in microspore and/or pollen, i.e., during male gametogenesis.
To assess the role of F-box protein genes during this crucial developmental step, we selected 34 F-box protein genes recorded as highly and specifically expressed in pollen and isolated corresponding insertion mutants.
We checked the expression level of each selected gene by RT-PCR and confirmed pollen expression for 25 genes, but specific expression for only 10 of the 34 F-box protein genes.
In addition, we tested the expression level of selected F-box protein genes in 24 mutant lines and showed that 11 of them were null mutants.
Transmission analysis of the mutations to the progeny showed that none of the single mutations was gametophytic lethal.
These unaffected transmission efficiencies suggested leaky mutations or functional redundancy among F-box protein genes.
Cytological observation of the gametophytes in the mutants confirmed these results.
Combinations of mutations in F-box protein genes from the same subfamily did not lead to transmission defect either, further highlighting functional redundancy and/or a high proportion of pseudogenes among these F-box protein genes. | 14,927 |
Title:
Factors that May Affect Treatment Outcome of Triple Helicobacter pylori Eradication Therapy with Omeprazole, Amoxicillin, and Clarithromycin
Abstract:
Factors affecting Helicobacter pylori eradication rate with omeprazole (OME), clarithromycin (CL), and amoxicillin (AMO) have not been extensively studied.
We have investigated the effect of age, sex, smoking, ulcer disease, compliance with therapy, H. pylori colonization density, degree and activity of antral gastritis, the coexistence of corpus gastritis, and the presence of lymphoid follicles on H. pylori eradication rate.
We studied 80 consecutive H. pylori-positive patients, with duodenal ulcer (N = 35) or nonulcer dyspepsia (N = 45) treated with OME 20 mg, CL 500 mg, and AMO 1 g, each given twice daily for 10 days.
H. pylori was eradicated in 71/80 (88.8%, 95% CI 82–96%) patients.
The regimen failed to eradicate the only strain (1.8%, 95% CI 0–5.2%) that was clarithromycin resistant.
Multivariate discriminant analysis showed that two histological variables (Wilks λ = 0.74, χ2 = 23.41, df = 2, P < 0.001), absence of lymphoid follicles in routine gastric biopsies (F = 13.63, P < 0.001) and coexistence of antral and body gastritis (F = 13.68, P < 0.001), significantly increased H. pylori eradication rate.
No other factor examined predicted H. pylori eradication with this regimen.
Our data suggest that body gastritis is a positive and presence of lymphoid follicles in routine gastric biopsies is a negative predictive factor of treatment outcome with the omeprazole, clarithromycin, and amoxicillin regime. | 14,942 |
Title:
Combined effects of nifekalant and lidocaine on the spiral-type re-entry in a perfused 2-dimensional layer of rabbit ventricular myocardium.
Abstract:
BACKGROUND ::: Spiral re-entry plays the principal role in the genesis of ventricular tachycardia and ventricular fibrillation (VT/VF).
The specific I(Kr) blocker, nifekakant (NIF) has, often in combination with lidocaine (LID), recently been used in Japan to prevent recurrent VT/VF, but the combined effects of these drugs on spiral re-entry had never been investigated.
::: ::: ::: METHODS AND RESULTS ::: A ventricular epicardial sheet was obtained from 13 Langendorff-perfused rabbit hearts by means of a cryoprocedure, and epicardial excitations were analyzed with a high-resolution optical mapping system.
Nifekakant (0.5 micromol/L) caused significant prolongation of action potential duration (APD) and LID (3 micromol/L) attenuated the APD prolongation without affecting the conduction velocity.
VT were induced in 6 hearts by cross-field stimulation, and single- or double-loop spirals circulating around variable functional block lines were visualized during the VT.
Nifekakant reduced VT cycle length and caused early termination in association with destabilization of the spiral dynamics (prolongation of functional block line, frequent local conduction block, and extensive meandering).
These modifications of spiral-type re-entrant VT by NIF were prevented by addition of LID.
::: ::: ::: CONCLUSIONS ::: The effects of NIF on the spiral excitations are reversed by LID.
This interaction should be taken into account when these drugs are used in combination to treat VT/VF. | 14,968 |
Title:
A phase I trial of antibody directed enzyme prodrug therapy (ADEPT) in patients with advanced colorectal carcinoma or other CEA producing tumours
Abstract:
Antibody-directed enzyme prodrug therapy is a targeted therapy in which a prodrug is activated selectively at the tumour site by an enzyme, which has been targeted to the tumour by an antibody (antibody-enzyme conjugate).
Previous clinical trials have shown evidence of tumour response, however, the activated drug had a long half-life, which resulted in dose-limiting myelosuppression.
Also, the targeting system, although giving high tumour to blood ratios of antibody-enzyme conjugate (10 000:1) required administration of a clearing antibody in addition to the antibody-enzyme conjugate.
The purpose of this current study therefore was to attempt tumour targeting of the antibody-enzyme conjugate without the clearing antibody, and to investigate a new prodrug (bis-iodo phenol mustard, ZD2767P) whose activated form is highly potent and has a short half-life.
Twenty-seven patients were treated with antibody-directed enzyme prodrug therapy using A5CP antibody-enzyme conjugate and ZD2767P prodrug, in a dose-escalating phase I trial.
The maximum tolerated dose of ZD2767P was reached at 15.5 mg m−2 × three administrations with a serum carboxypeptidase G2 level of 0.05 U ml−1.
Myelosuppression limited dose escalation.
Other toxicities were mild.
Patients' quality of life was not adversely affected during the trial as assessed by the measures used.
There were no clinical or radiological responses seen in the study, but three patients had stable disease at day 56.
Human anti-mouse antibody and human anti-carboxypeptidase G2 antibody were produced in response to the antibody enzyme conjugate (A5CP).
The antibody-enzyme conjugate localisation data (carboxypeptidase G2 enzyme levels by HPLC on tumour and normal tissue samples, and gamma camera analysis of I-131 radiolabelled conjugate) are consistent with inadequate tumour localisation (median tumour: normal tissue ratios of antibody-enzyme conjugate of less than 1).
A clearance system is therefore desirable with this antibody-enzyme conjugate or a more efficient targeting system is required.
ZD2767P was shown to clear rapidly from the circulation and activated drug was not measurable in the blood.
ZD2767P has potential for use in future antibody-directed enzyme prodrug therapy systems. | 15,042 |
Title:
Helminth infections in small mammals from Ulu Gombak Forest Reserve and the risk to human health.
Abstract:
A survey for small mammal parasites carried out in a secondary forest of Ulu Gombak, Selangor, Peninsula Malaysia yielded the following animals: Rattus bowersi (7), Rattus tiomanicus jalorensis (2), Maxomys rajah (12), Maxoyms whiteheadi (3), Leopoldamys sabanus(13), Sundamys muelleri(10), Lariscus insignis (1), Sundasciurus tenuis (1) and Tupaia glis (2).
The following nematodes: Capillaria hepatica, Hepatojarakus malayae, Trichostrongylus sp. and Streptopharagus sp., the following cestodes: Hymenolepis sp., Raillietina sp. and Taenia taeniaformis; and trematode, Zonorchis sp. from Tupaia glis were recovered.
No parasites were observed during blood examination.
No endoparasite was seen in Maxomys whiteheadi, Lariscus insignis and Sundasciurus tenuis.
The following parasites, Capillaria hepatica, Hymenolepis sp., Raillietina sp. and Taenia taeniaformis are considered of medical importance. | 15,075 |
Title:
The new heterologous fibrin sealant in combination with low-level laser therapy (LLLT) in the repair of the buccal branch of the facial nerve
Abstract:
This study aimed to evaluate the effects of low-level laser therapy (LLLT) in the repair of the buccal branch of the facial nerve with two surgical techniques: end-to-end epineural suture and coaptation with heterologous fibrin sealant.
Forty-two male Wistar rats were randomly divided into five groups: control group (CG) in which the buccal branch of the facial nerve was collected without injury; (2) experimental group with suture (EGS) and experimental group with fibrin (EGF): The buccal branch of the facial nerve was transected on both sides of the face.
End-to-end suture was performed on the right side and fibrin sealant on the left side; (3) Experimental group with suture and laser (EGSL) and experimental group with fibrin and laser (EGFL).
All animals underwent the same surgical procedures in the EGS and EGF groups, in combination with the application of LLLT (wavelength of 830 nm, 30 mW optical power output of potency, and energy density of 6 J/cm(2)).
The animals of the five groups were euthanized at 5 weeks post-surgery and 10 weeks post-surgery.
Axonal sprouting was observed in the distal stump of the facial nerve in all experimental groups.
The observed morphology was similar to the fibers of the control group, with a predominance of myelinated fibers.
In the final period of the experiment, the EGSL presented the closest results to the CG, in all variables measured, except in the axon area.
Both surgical techniques analyzed were effective in the treatment of peripheral nerve injuries, where the use of fibrin sealant allowed the manipulation of the nerve stumps without trauma.
LLLT exhibited satisfactory results on facial nerve regeneration, being therefore a useful technique to stimulate axonal regeneration process. | 15,085 |
Title:
Heterosynaptic Plasticity Underlies Aversive Olfactory Learning in Drosophila
Abstract:
Summary Although associative learning has been localized to specific brain areas in many animals, identifying the underlying synaptic processes in vivo has been difficult.
Here, we provide the first demonstration of long-term synaptic plasticity at the output site of the Drosophila mushroom body.
Pairing an odor with activation of specific dopamine neurons induces both learning and odor-specific synaptic depression.
The plasticity induction strictly depends on the temporal order of the two stimuli, replicating the logical requirement for associative learning.
Furthermore, we reveal that dopamine action is confined to and distinct across different anatomical compartments of the mushroom body lobes.
Finally, we find that overlap between sparse representations of different odors defines both stimulus specificity of the plasticity and generalizability of associative memories across odors.
Thus, the plasticity we find here not only manifests important features of associative learning but also provides general insights into how a sparse sensory code is read out. | 15,225 |
Title:
The efficacy and safety of crizotinib in the treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer: a meta-analysis of clinical trials
Abstract:
BackgroundCrizotinib was granted accelerated approval by the Food and Drug Administration in 2011 for the treatment of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).
To evaluate the efficacy and safety of crizotinib, we performed a meta-analysis of published clinical trials using the random effect model.
MethodsThe efficacy and safety of crizotinib was evaluated based on 1-year overall survival (OS), progression-free survival (PFS), overall response rate (ORR), partial response, complete response, stable disease, and dose reduction or cessation because of crizotinib toxicity.
ResultsSix clinical trials were included in the meta-analysis.
Crizotinib treatment demonstrated a 1-year OS of 66.8% (95% CI, 52.2–78.8%) and a PFS of 8.6 months (95% CI, 7.3–9.9 months).
The aggregate ORR, partial response and complete response rates were 61.2%, 59.8% and 1.5%, respectively.
The proportion of patients achieving stable disease was 42.6% (95% CI, 17.3–72.5%).
The most frequently reported adverse effects of crizotinib were mild visual disturbances, nausea, vomiting, diarrhea, constipation, edema, reduction in glomerular filtration rate, and generally reversible but sometimes severe elevations in aspartate aminotransferase and alanine aminotransferase.
The proportion of patients who required dose reduction or cessation because of crizotinib toxicity was 6.5% (95% CI, 4.1–10.1%).ConclusionsThis meta-analysis revealed extended survival and improved response rates in patients treated with crizotinib.
As a novel, targeted anticancer agent, crizotinib appears to be a favorable treatment option for patients with locally advanced or metastatic ALK-positive NSCLC. | 15,228 |
Title:
Early Experience With (Dry) Arthroscopic 4-Corner Arthrodesis: From a 4-Hour Operation to a Tourniquet Time
Abstract:
Purpose Scaphoidectomy and 4-corner arthrodesis (4CA) is an effective procedure for treating several degenerative conditions of the wrist.
Recently, the arthroscopic approach to this operation was described.
Although it is conceptually appealing, certain aspects make its application difficult.
We present our technique for dry arthroscopic scaphoidectomy and 4CA, which reduces the operative time to less than 2 hours.
Methods Four consecutive patients underwent scaphoidectomy and 4CA.
In each case, we performed the operation with a dry arthroscopic technique using cannulated screws for rigid fixation.
We performed bone grafting from the distal radius in 2 patients and from the scaphoid itself in the other two.
The relevant operative details are the use of a scapholunate portal, the resection of the scaphoid with a pituitary rongeur, and the placement of bone graft in a dry arthroscopic environment.
Range of motion exercises are started 2 to 3 weeks after the operation.
Results The first operation took 4 hours.
The last 2 were completed in 1 hour 45 minutes and 1 hour 55 minutes, respectively.
No complications occurred.
No operations were converted to an open procedure.
Conclusions Although the operation has a steep learning curve, it is conceptually appealing.
It is too early to prove that the arthroscopic procedure has better results than the open 4CA; nevertheless, in our opinion it represents the future of wrist surgery. | 15,240 |
Title:
Carinal resection and reconstruction for recurrent lung cancer
Abstract:
A patient with a recurrent tumor in the trachea adjacent to the right main bronchus was treated by surgical resection 19 months after undergoing surgery for the primary cancer.
The patient had previously undergone right upper lobectomy for T1N0M0 stage I squamous cell carcinoma.
A carinal resection was performed which included 4 rings of the trachea, 2 rings of the righ main bronchus, and 1 ring of the left main bronchus.
Reconstruction consisted of an end-to-end anastomosis of the trachea and left main bronchus, and an end-to-side anastomosis of the right and left main bronchi.
The postoperative course was uneventful, and at present the patient is healthy 12 months following reoperation. | 15,477 |
Title:
Unfattening our children: forks over feet
Abstract:
Childhood obesity rates have risen alarmingly for decades, and although recent data suggest a possible plateau, obesity is seen in ever younger children, and is increasingly severe.
The proximal cause of obesity is energy imbalance; the root cause is modern living.
Throughout most of human history, calories were relatively scarce and hard to get, and physical activity unavoidable.
We have devised a modern world, in which physical activity is scarce and hard to get and calories are unavoidable.
Although both sides of the energy balance equation matter, forced to pick sides, we should prioritize forks over feet for weight control based on both science and sense.
The modern world makes it very easy to out-eat exercise, and nearly impossible to out-exercise excessive eating. | 15,486 |
Title:
Molecular characterization and phylogenetic utility of the rDNA external transcribed spacer region in Stylosanthes (Fabaceae)
Abstract:
Supplementary Material The nucleotide sequence of the ribosomal external transcribed spacer (ETS) region of Stylosanthes mexicana was determined and used to evaluate its potential for examination of intra- and inter-specific relationships in Stylosanthes, as compared to the use of the internal transcribed spacer (ITS) region.
The entire ETS region comprises 1,145 bp and is composed of a region of non-repetitive sequences consisting of three subregions with organizational and nucleotide-sequence conservation, and a triplicated segment of about 100 bp.
A primer designed in the second conserved subregion allowed us to amplify and sequence directly the 3' part (423-431 bp) of the ETS from 22 genotypes of 12 representative Stylosanthes species that were previously used in phylogenetic analysis of the genus.
The study revealed that the right-hand part of Stylosanthes ETS contains approximately twice as much variable and informative characters than the ITS.
Moreover, pairwise sequence-divergence values are twice as high, on average, when compared to the ITS.
The ITS and ETS datasets are consistent in phylogenetic reconstruction of Stylosanthes, and combined parsimony analysis resulted in a strict consensus tree that is better resolved and generally better supported than trees obtained from separate analysis of the spacer regions. | 15,645 |
Title:
Barriers and facilitators to the use of computer-based intensive insulin therapy
Abstract:
Abstract Purpose Computerized clinical decision support systems (CDSSs) for intensive insulin therapy (IIT) are increasingly common.
However, recent studies question IIT's safety and mortality benefit.
Researchers have identified factors influencing IIT performance, but little is known about how workflow affects computer-based IIT.
We used ethnographic methods to evaluate IIT CDSS with respect to other clinical information systems and care processes.
Methods We conducted direct observation of and unstructured interviews with nurses using IIT CDSS in the surgical and trauma intensive care units at an academic medical center.
We observed 49 h of intensive care unit workflow including 49 instances of nurses using IIT CDSS embedded in a provider order entry system.
Observations focused on the interaction of people, process, and technology.
By analyzing qualitative field note data through an inductive approach, we identified barriers and facilitators to IIT CDSS use.
Results Barriers included (1) workload tradeoffs between computer system use and direct patient care, especially related to electronic nursing documentation, (2) lack of IIT CDSS protocol reminders, (3) inaccurate user interface design assumptions, and (4) potential for error in operating medical devices.
Facilitators included (1) nurse trust in IIT CDSS combined with clinical judgment, (2) nurse resilience, and (3) paper serving as an intermediary between patient bedside and IIT CDSS.
Conclusion This analysis revealed sociotechnical interactions affecting IIT CDSS that previous studies have not addressed.
These issues may influence protocol performance at other institutions.
Findings have implications for IIT CDSS user interface design and alerts, and may contribute to nascent general CDSS theory. | 15,738 |
Title:
Modulation of human longevity by SIRT3 single nucleotide polymorphisms in the prospective study “Treviso Longeva (TRELONG)”
Abstract:
Human sirtuins are seven proteins with deacetylase activity that are emerging as key modulators of basic physiological functions.
Some evidence links SIRT3 to longevity in mammals.
This study aimed to investigate whether variants within SIRT3 gene were associated to human longevity.
We analyzed 549 genomic DNA collected during the prospective study “Treviso Longeva,” including elderly over 70 years of age from the municipality of Treviso, a small city in the northeast of Italy.
We genotyped SIRT3 rs3825075, rs4980329, and rs11555236 single nucleotide polymorphisms (SNPs) by real-time polymerase chain reaction allelic discrimination assay.
A cross-sectional analysis performed by comparing people over and under 85 years of age did not evidence association among the SIRT3 SNPs and longevity.
However, when we performed a longitudinal analysis considering mortality as a dependent variable, we observed an association of SIRT3 rs11555236 and rs4980329 with longevity in the whole population (p values corrected for potential confounders = 0.04 and 0.03, respectively).
After stratification according to gender, the same SNPs were associated to female longevity only (p values corrected for potential confounders = 0.03 and 0.02, respectively).
Finally, as rs11555236 was reported to be in linkage disequilibrium with a putative functional enhancer within the SIRT3 gene, we assessed whether rs11555236 genotypes correlated with a different level of SIRT3 protein in peripheral blood mononuclear cells.
We found an increased level of SIRT3 in subjects homozygous for the (T) allele.
We suggest that SIRT3 genetic variability might be relevant for the modulation of human longevity in the Italian population. | 15,762 |
Title:
Inducible nitric oxide synthase and cytokine pattern in lesions of patients with American cutaneous leishmaniasis.
Abstract:
American tegumentary leishmaniasis has three forms: localized (LCL), found in resistant individuals; diffuse (DCL), found in susceptible individuals; and intermediate cutaneous leishmaniasis (ICL), found in individuals with exacerbated immunity.
We evaluated cytokines and inducible nitric oxide synthase (iNOS) in lesions of LCL, ICL and DCL using immunohistochemistry.
LCL granulomas showed a preponderance of interferon (IFN)-gamma and interleukin (IL)-12 expression, whereas ICL granulomas had more IL-4-, IL-10- and mainly transforming growth factor (TGF)-beta1-expressing cells.
Higher densities of iNOS+ cells were observed in ICL and LCL than in DCL.
iNOS was also expressed in keratinocytes of LCL and ICL lesions, and in epidermal dendritic cells of ICL lesions.
In LCL and ICL, most keratinocytes expressed IL-12 and a portion expressed IFN-gamma.
IL-12+ and IFN-gamma+ dendritic cells were absent or sparse in LCL and ICL epidermis.
Our results show the importance of iNOS, IL-12 and INF-gamma in LCL and ICL lesions, emphasizing the existence of a mixed cytokine pattern in ICL different from the Th1 and Th2 responses established in LCL and DCL lesions. | 15,830 |
Title:
Secondary product glycosyltransferases in seeds of Brassica napus
Abstract:
This study describes a systematic screen for secondary product UDP-glycosyltransferases (UGTs; EC 2.4.1) involved in seed development of oilseed rape (Brassica napus) and was aimed at identifying genes related to UGT84A9 encoding UDP-glucose:sinapate glucosyltransferase (EC 2.4.1.120), a proven target for molecular breeding approaches to reduce the content of anti-nutritive sinapate esters.
By RT-PCR with primers recognizing the conserved signature motif of UGTs, 13 distinct ESTs could be generated from seed RNA.
Sequence analysis allowed to assign the isolated ESTs to groups B, D, E, and L of the UGT family.
In an alternative approach, two open reading frames related to UGT84A9 were cloned from the B. napus genome and designated as UGT84A10 and UGT84A11, respectively.
Functional expression of UGT84A10 revealed that the encoded enzyme catalyzes the formation of 1-O-acylglucosides (β-acetal esters) with several hydroxycinnamates whereas, in our hands, the recombinant UGT84A11 did not display this enzymatic activity.
Semi-quantitative RT-PCR confirmed that the majority of potential UGTs specified by the isolated ESTs is differentially expressed.
A pronounced transcriptional up-regulation during seed development was evident for UGT84A9 and one EST (BnGT3) clustering in group E of UGTs.
UGT84A10 was highly induced in flowers and expressed to a moderate level in late seed maturation indicating a possible involvement in seed-specific sinapate ester biosynthesis. | 15,845 |
Title:
Serum Immunoglobulin G Antibodies to Chlamydial Heat Shock Protein 60 but Not to Human and Bacterial Homologs Are Associated With Coronary Artery Disease
Abstract:
BACKGROUND ::: Evidence for an association between Chlamydia pneumoniae infection and coronary artery disease (CAD) has been reported by numerous studies, cross-reactive heat shock protein (Hsp) antibody responses have been causally linked to CAD, and the severity of chlamydial disease pathogenesis correlates with Hsp serology.
Our aim was to determine if chlamydial Hsp (cHsp) antibody responses are predictive of CAD. ::: ::: ::: METHODS AND RESULTS ::: Patients were recruited in a case-control study: 250 cases had angiographically significant CAD (stenosis > or =70%), and 250 controls had normal coronary arteries (stenosis <10%).
Serum immunoglobulin G reactivity to Hsp10 and Hsp60 antigens (chlamydial, Escherichia coli, and human), and C pneumoniae whole organisms were measured by ELISA.
Univariate analysis confirmed that classical CAD risk factors were predictors of CAD.
Univariate analysis showed that cHsp60 (P= 0.001, OR 3.9), cHsp10 (P=0.045, OR 3.8), E coli Hsp60 (P=0.04, OR 1.5) and C pneumoniae (P=0.03, OR 1.8) ELISA optical density (OD) values were significantly different between cases and controls.
Multivariate analysis found that only upper-quintile cHsp60 seroreactivity remained a significant predictor of CAD after controlling for classical CAD risk factors and seroreactivity to the other antigens (cHsp60 OD, P=0.005, OR 3.9 per OD unit; cHsp60 quintile, 5 versus 1 to 4; P=0.01, OR 2.1). ::: ::: ::: CONCLUSIONS ::: The presence of elevated anti-cHsp60 immunoglobulin G antibodies, but not anti-human or anti-E coli homologs, was independently associated with CAD.
This finding argues against previous suggestions that cross-reactive or autoimmune Hsp60 responses may contribute to disease progression.
High anti-cHsp60 antibody response appears to identify the subset of patients with chlamydial infection and significant CAD. | 16,104 |
Title:
Effect of Formulation- and Administration-Related Variables on Deposition Pattern of Nasal Spray Pumps Evaluated Using a Nasal Cast
Abstract:
PURPOSE ::: To systematically evaluate the effect of formulation- and administration-related variables on nasal spray deposition using a nasal cast. ::: ::: ::: METHODS ::: Deposition pattern was assessed by uniformly coating a transparent nose model with Sar-Gel®, which changes from white to purple on contact with water.
Sprays were subsequently discharged into the cast, which was then digitally photographed.
Images were quantified using Adobe® Photoshop.
The effects of formulation viscosity (which influences droplet size), simulated administration techniques (head orientation, spray administration angle, spray nozzle insertion depth), spray pump design and metering volume on nasal deposition pattern were investigated.
::: ::: ::: RESULTS ::: There was a significant decrease in the deposition area associated with sprays of increasing viscosity.
This appeared to be mediated by an increase in droplet size and a narrowing of the spray plume.
Administration techniques and nasal spray pump design also had a significant effect on the deposition pattern. ::: ::: ::: CONCLUSIONS ::: This simple color-based method provides quantitative estimates of the effects that different formulation and administration variables may have on the nasal deposition area, and provides a rational basis on which manufacturers of nasal sprays can base their patient instructions or post approval changes when it is impractical to optimize these using a clinical study. | 16,150 |
Title:
Diffusion with Stochastic Resetting
Abstract:
We study simple diffusion where a particle stochastically resets to its initial position at a constant rate r. A finite resetting rate leads to a nonequilibrium stationary state with non-Gaussian fluctuations for the particle position.
We also show that the mean time to find a stationary target by a diffusive searcher is finite and has a minimum value at an optimal resetting rate r^*. Resetting also alters fundamentally the late time decay of the survival probability of a stationary target when there are multiple searchers: while the typical survival probability decays exponentially with time, the average decays as a power law with an exponent depending continuously on the density of searchers. | 16,259 |
Title:
A soybean 101-kD heat shock protein complements a yeast HSP104 deletion mutant in acquiring thermotolerance. Plant Cell 6
Abstract:
A cDNA clone encoding a 101-kD heat shock protein (HSP101) of soybean was isolated and sequenced.
Genomic DNA gel blot analysis indicated that the corresponding gene is a member of a multigene family.
The mRNA for HSP101 was not detected in 2-day-old etiolated soybean seedlings grown at 28 degrees C but was induced by elevated temperatures.
DNA sequence comparison has shown that the corresponding gene belongs to the Clp (caseinolytic protease) (or Hsp100) gene family, which is evolutionarily conserved and found in both prokaryotes and eukaryotes.
On the basis of the spacer length between the two conserved ATP binding regions, this gene has been identified as a member of the ClpB subfamily.
Unlike other Clp genes previously isolated from higher plants, the expression of this soybean Hsp101 gene is heat inducible, and it does not have an N-terminal signal peptide for targeting to chloroplasts.
Transformation of the soybean Hsp101 gene into a yeast HSP104 deletion mutant complemented restoration of acquired thermotolerance, a process in which cells survive an otherwise lethal heat stress after they are given a permissive heat treatment. | 16,268 |
Title:
Child Abuse and Orthopaedic Injury Patterns: Analysis at a Level I Pediatric Trauma Center
Abstract:
BACKGROUND: Child abuse is a serious threat to the physical and psychosocial well-being of the pediatric population.
Musculoskeletal injuries are common manifestations of child abuse.
There have been multiple studies that have attempted to identify the factors associated with, and the specific injury patterns seen with musculoskeletal trauma from child abuse, yet there have been no large studies that have used prospectively collected data and controlled comparisons.
The purpose of our study was to describe the patterns of orthopaedic injury for child abuse cases detected in the large urban area that our institution serves, and to compare the injury profiles of these victims of child abuse to that of general (accidental) trauma patients seen in the emergency room and/or hospitalized during the same time period.
METHODS: This study is a retrospective review of prospectively collected information from an urban level I pediatric trauma center.
Five hundred cases of child abuse (age birth to 48 mo) were identified by membership in our institution's Suspected Child Abuse and Neglect database collected between 1998 and 2007.
These cases were compared against 985 general trauma (accidental) control patients of the same age group from 2000 to 2003.
Age, sex, and injury type were compared.
RESULTS: Victims of child abuse were on average younger than accidental trauma patients in the cohort of patients under 48 months of age.
There was no difference in sex distribution between child abuse and accidental trauma patients.
When the entire cohort of patients under 48 months were examined after adjusting for age and sex, the odds of rib (14.4 times), tibia/fibula (6.3 times), radius/ulna (5.8 times), and clavicle fractures (4.4 times) were significantly higher in child abuse versus accidental trauma patients.
When regrouping the data based on age, in patients younger than 18 months of age, the odds of rib (23.7 times), tibia/fibula (12.8 times), humerus (2.3 times), and femur fractures (1.8 times) were found to be significantly higher in the child abuse group.
Yet, in the more than 18 months age group, the risk of humerus (3.4 times) and femur fractures (3.3 times) was actually higher in the accidental trauma group than in the child abuse group.
CONCLUSIONS: Patients who present to an urban level I pediatric trauma center and are victims of abuse are generally younger, and have an equal propensity to be male or female.
It is important for the clinician to recognize that the age of the patient (younger or older than 18 mo and/or walking age) is an important determinant in identifying injury patterns suspicious for abuse.
Patients below the age of 18 months who present with rib, tibia/fibula, humerus, or femur fractures are more likely to be victims of abuse than accidental trauma patients.
Yet, when patients advance in age beyond 18 months, their presentation with long bone fractures (ie, femur and humerus) is more likely to be related to accidental trauma than child abuse.
Language: en | 16,326 |
Title:
Cleaved/Associated TLR3 Represents the Primary Form of the Signaling Receptor
Abstract:
TLR3 belongs to the family of intracellular TLRs that recognize nucleic acids.
Endolysosomal localization and cleavage of intracellular TLRs play pivotal roles in signaling and represent fail-safe mechanisms to prevent self-nucleic acid recognition.
Indeed, cleavage by cathepsins is required for native TLR3 to signal in response to dsRNA.
Using novel Abs generated against TLR3, we show that the conserved loop exposed in LRR12 is the single cleavage site that lies between the two dsRNA binding sites required for TLR3 dimerization and signaling.
Accordingly, we found that the cleavage does not dissociate the C- and N-terminal fragments, but it generates a very stable "cleaved/associated" TLR3 present in endolysosomes that recognizes dsRNA and signals.
Moreover, comparison of wild-type, noncleavable, and C-terminal-only mutants of TLR3 demonstrates that efficient signaling requires cleavage of the LRR12 loop but not dissociation of the fragments.
Thus, the proteolytic cleavage of TLR3 appears to fulfill function(s) other than separating the two fragments to generate a functional receptor. | 16,345 |
Title:
Thrombosis after kidney transplantation.
Abstract:
The diagnosis of deep vein thrombosis (DVT) is unusual in patients with sickle cell disease (SCD).
Despite the incidence of cerebral thrombosis in SCD patients due to vasooclusion, thrombotic manifestations in peripheral vessels are rare.
Patients with homozygous SCD present a variety of renal abnormalities as a result of sickle crisis.
In this group of patients, kidney transplantation has been performed in the renal endstage patients; with graft survival rates similar to that of the general transplant population at 1 year.
However, patients with SCD experience an augmentation in the frequency of painful crises in the first year after transplantation, which has been attributed to concurrent elevations in hematocrit and plasma viscosity.
Despite etiology, renal transplant patients are at increased risk for the development of thromboembolic events such as deep vein thrombosis and renovascular thrombosis after allograft procedure.
These events can be due to a prothrombotic state generated by the use of immunosuppressive agents.
Although other factors such as acquired or inherited disorders of the clotting system may increase the risk of thrombosis.
Here, we report a case of a renal transplant patient with sickle cell disease who presented recurrent episodes of DVT and increase painful sickle episodes after kidney transplantation. | 16,389 |
Title:
Attributing Effects to Interactions
Abstract:
A framework is presented that allows an investigator to estimate the portion of the effect of one exposure that is attributable to an interaction with a second exposure.
We show that when the 2 exposures are statistically independent in distribution, the total effect of one exposure can be decomposed into a conditional effect of that exposure when the second is absent and also a component due to interaction.
The decomposition applies on difference or ratio scales.
We discuss how the components can be estimated using standard regression models, and how these components can be used to evaluate the proportion of the total effect of the primary exposure attributable to the interaction with the second exposure.
In the setting in which one of the exposures affects the other, so that the 2 are no longer statistically independent in distribution, alternative decompositions are discussed.
The various decompositions are illustrated with an example in genetic epidemiology.
If it is not possible to intervene on the primary exposure of interest, the methods described in this article can help investigators to identify other variables that, if intervened upon, would eliminate the largest proportion of the effect of the primary exposure. | 16,469 |
Title:
Spectral and Spatial-Based Classification for Broad-Scale Land Cover Mapping Based on Logistic Regression
Abstract:
Improvement of satellite sensor characteristics motivates the development of new techniques for satellite image classification.
Spatial information seems to be critical in classification processes, especially for heterogeneous and complex landscapes such as those observed in the Mediterranean basin.
In our study, a spectral classification method of a LANDSAT-5 TM imagery that uses several binomial logistic regression models was developed, evaluated and compared to the familiar parametric maximum likelihood algorithm.
The classification approach based on logistic regression modelling was extended to a contextual one by using autocovariates to consider spatial dependencies of every pixel with its neighbours.
Finally, the maximum likelihood algorithm was upgraded to contextual by considering typicality, a measure which indicates the strength of class membership.
The use of logistic regression for broad-scale land cover classification presented higher overall accuracy (75.61%), although not statistically significant, than the maximum likelihood algorithm (64.23%), even when the latter was refined following a spatial approach based on Mahalanobis distance (66.67%).
However, the consideration of the spatial autocovariate in the logistic models significantly improved the fit of the models and increased the overall accuracy from 75.61% to 80.49%. | 16,485 |
Title:
MDR1 P-Glycoprotein Is a Lipid Translocase of Broad Specificity, While MDR3 P-Glycoprotein Specifically Translocates Phosphatidylcholine
Abstract:
Abstract The human MDR1 P-glycoprotein (Pgp) extrudes a variety of drugs across the plasma membrane.
The homologous MDR3 Pgp is required for phosphatidylcholine secretion into bile.
After stable transfection of epithelial LLC-PK1 cells, MDR1 and MDR3 Pgp were localized in the apical membrane.
At 15°C, newly synthesized short-chain analogs of various membrane lipids were recovered in the apical albumin-containing medium of MDR1 cells but not control cells.
MDR inhibitors and energy depletion reduced apical release.
MDR3 cells exclusively released a short-chain phosphatidylcholine.
Since no vesicular secretion occurs at 15°C, the short-chain lipids must have been translocated by the Pgps across the plasma membrane before extraction into the medium by the lipid-acceptor albumin. | 16,488 |
Title:
Consistent avoidance of human disturbance over large geographical distances by a migratory bird
Abstract:
Recent work on animal personalities has demonstrated that individuals may show consistent behaviour across situations and contexts.
These studies were often carried out in one location and/or during short time intervals.
Many animals, however, migrate and spend their life in several geographically distinct locations, and they may either adopt behaviours specific to the local environment or keep consistent behaviours over ecologically distinct locations.
Long-distance migratory species offer excellent opportunities to test whether the animals maintain their personalities over large geographical scale, although the practical difficulties associated with these studies have hampered such tests.
Here, we demonstrate for the first time consistency in disturbance tolerance behaviour in a long-distance migratory bird, using the common crane Grus grus as an ecological model species.
Cranes that hatched in undisturbed habitats in Finland choose undisturbed migratory stop-over sites in Hungary, 1300-2000 km away from their breeding ground.
This is remarkable, because these sites are not only separated by large distances, they also differ ecologically: the breeding sites are wooded bogs and subarctic tundra, whereas the migratory stop-over sites are temperate zone alkaline grasslands.
The significance of our study goes beyond evolutionary biology and behavioural ecology: local effects on behaviour may carry over large distances, and this hitherto hidden implication of habitat selection needs to be incorporated into conservation planning. | 16,520 |
Title:
Confirmation that MAT1A p.Ala259Val mutation causes autosomal dominant hypermethioninemia
Abstract:
Methionine adenosyltransferase (MAT) I/III deficiency is an inborn error of metabolism caused by mutations in MAT1A, encoding the catalytic subunit of MAT responsible for the synthesis of S-adenosylmethionine, and is characterized by persistent hypermethioninemia.
While historically considered a recessive disorder, a milder autosomal dominant form of MAT I/III deficiency occurs, though only the most common mutation p.
Arg264His has ample evidence to prove dominant inheritance.
We report a case of hypermethioninemia caused by the p.
Ala259Val substitution and provide evidence of autosomal dominant inheritance by showing both maternal inheritance of the mutation and concomitant hypermethioninemia.
The p.
Ala259Val mutation falls in the dimer interface, and thus likely leads to dominant inheritance by a similar mechanism to that described in the previously reported dominant negative mutation, that is, by means of interference with subunits encoded by the wild-type allele. | 16,540 |
Title:
Pre-treatment with a Xingnaojing preparation ameliorates sevoflurane-induced neuroapoptosis in the infant rat striatum
Abstract:
Xingnaojing (XNJ), is a standardized Chinese herbal medicine product derived from An Gong Niu Huang Pill.
It may be involved in neuroprotection in a number of neurological disorders.
Exposure to anesthetic agents during the brain growth spurt may trigger widespread neuroapoptosis in the developing brain.
Thus the present study aimed to identify whether there was a neuroprotective effect of XNJ on anesthesia-induced neuroapoptosis.
Seven-day-old rats received treatment with 2.1% sevoflurane for 6 h. Rat pups were injected intraperitoneally with 1 or 10 ml/kg XNJ at 0.2, 24 and 48 h prior to sevoflurane exposure.
The striata of neonatal rats were collected following administration of anesthesia.
Western blotting and immunohistochemistry were used to analyze the expression of activated caspase 3, Bax and phosphorylated protein kinase B (p-AKT) in the striatum.
It was found that activated caspase 3 and Bax expression were upregulated in the striatum following sevoflurane treatment.
Preconditioning with XNJ attenuated the neuronal apoptosis induced by sevoflurane in a dose-dependent manner.
Anesthesia reduced the expression of p-AKT (phosphorylated at sites Thr308 and Ser473) and phosphorylated extracellular-regulated protein kinase (p-ERK) in the striatum.
Pre-treatment with XNJ reversed the reduction in p-AKT, but not p-ERK expression.
These data suggest that XNJ has an antiapoptotic effect against sevoflurane-induced cell loss in the striatum.
It thus holds promise as a safe and effective neuroprotective agent.
The action of XNJ on p-AKT may make a significant contribution to its neuroprotective effect. | 16,582 |
Title:
Estrogenic Potency of Benzophenone UV Filters in Breast Cancer Cells: Proliferative and Transcriptional Activity Substantiated by Docking Analysis
Abstract:
The results from recent studies show that some benzophenones (BPs) and their hydroxylated metabolites can function as weak estrogens (E2) in the environment.
However, little is known about the structure-activity relationship of these molecules.
We have examined the effects of exposure to ten different BPs on the proliferation of estrogen receptor (ER)-positive breast cancer cells and on the transcriptional activity of E2-target genes.
We analyzed two genes that are tightly linked with estrogen-mediated proliferation, the CXCL12 and amphiregulin genes and two classical estrogen-responsive genes, the pS2 and progesterone receptor.
Significant differences in the BPs efficiency to induce cell proliferation and endogenous E2-target gene expressions were observed.
Using ERE-, Sp1-, AP1- and C3-reporter genes that contain different ER-binding sites in their promoter, we also showed significant differences in the BPs efficiency in activation of the ER transactivation.
Together, our analyzes showed that the most active molecule is 4-hydroxy-BP.
Docking analysis of the interaction of BPs in the ligand-binding pocket of ERα suggests that the minimum structural requirement for the estrogenic activity of BPs is a hydroxyl (OH) group in the phenyl A-ring that allows interaction with Glu-353, Arg-394 or Phe-404, which enhances the stability between BPs and ERα.
Our modeling also indicates a loss of interaction between the OH groups of the phenyl B-ring and His-524.
In addition, the presence of some OH groups in the phenyl B-ring can create repulsion forces, which may constrain helix 12 in an unfavorable position, explaining the differential estrogenic effects of BPs.
These results, together with our analysis of BPs for their potency in activation of cell proliferation and ER-mediated transcription, report an improved understanding of the mechanism and structure–activity relationship of BPs. | 16,604 |
Title:
Distinct Expression Pattern of Microtubule-Associated Protein-2 in Human Oligodendrogliomas and Glial Precursor Cells
Abstract:
Microtubule-associated protein 2 (MAP2), a protein linked to the neuronal cytoskeleton in the mature central nervous system (CNS), has recently been identified in glial precursors indicating a potential role during glial development.
In the present study, we systematically analyzed the expression of MAP2 in a series of 237 human neuroepithelial tumors including paraffin-embedded specimens and tumor tissue microarrays from oligodendrogliomas, mixed gliomas, astrocytomas, glioblastomas, ependymomas, as well as dysembryoplastic neuroepithelial tumors (DNT), and central neurocytomas.
In addition, MAP2-immunoreactive precursor cells were studied in the developing human brain.
Three monoclonal antibodies generated against MAP2A-B or MAP2A-D isoforms were used.
Variable immunoreactivity for MAP2 could be observed in all gliomas with the exception of ependymomas.
Oligodendrogliomas exhibited a consistently strong and distinct pattern of expression characterized by perinuclear cytoplasmic staining without significant process labeling.
Tumor cells with immunoreactive bi- or multi-polar processes were mostly encountered in astroglial neoplasms, whereas the small cell component in neurocytomas and DNT was not labeled.
These features render MAP2 immunoreactivity a helpful diagnostic tool for the distinction of oligodendrogliomas and other neuroepithelial neoplasms.
RT-PCR, Western blot analysis, and in situ hybridization confirmed the expression of MAP2A-C (including the novel MAP2+13 transcript) in both oligodendrogliomas and astrocytomas.
Double fluorescent laser scanning microscopy showed that GFAP and MAP2 labeled different tumor cell populations.
In embryonic human brains, MAP2-immunoreactive glial precursor cells were identified within the subventricular or intermediate zones.
These precursors exhibit morphology closely resembling the immunolabeled neoplastic cells observed in glial tumors.
Our findings demonstrate MAP2 expression in astrocytic and oligodendroglial neoplasms.
The distinct pattern of immunoreactivity in oligodendrogliomas may be useful as a diagnostic tool.
Since MAP2 expression occurs transiently in migrating immature glial cells, our findings are in line with an assumed origin of diffuse gliomas from glial precursors. | 16,613 |
Title:
Prospective randomized double-blind trial of nabilone versus domperidone in the treatment of cytotoxic-induced emesis
Abstract:
A prospective randomized double-blind trial comparing the butyrophenone analogue domperidone (D) and the synthetic cannabinoid nabilone (N) in the treatment of cytotoxic-induced emesis was conducted in 38 patients receiving highly emetogenic chemotherapy regimens (70% containing cisplatin).
Patients received 20 mg D or 1 mg N the night before chemotherapy and 8-hourly on each chemotherapy day for two consecutive cycles of treatment.
Three of 19 patients randomized to N completed only one cycle because of disease progression or subjectively adverse effects.
Four of 19 patients completed only one cycle of D because of lack of efficacy or chemotherapy toxicity.
In all, 32 cycles of N and 33 cycles of D were evaluable for efficacy.
The mean number of vomiting episodes in cycle 1 was 4.76 for N and 12.95 for D (P less than 0.02).
The corresponding values for cycle 2 were 4.27 and 7.69 (P greater than 0.10), and for cycles 1 and 2 combined, 4.53 for N and 10.81 for D (P less than 0.01).
Nausea and food intake scores did not differ significantly, although there was a trend towards less nausea and an increased food intake with N. Subjectively adverse effects were more frequent with N and included drowsiness, dizziness, dry mouth, and postural hypotension.
N is superior to D for the control of cytotoxic-induced emesis. | 16,616 |
Title:
Excess gains in weight and waist circumference associated with childbearing: The Coronary Artery Risk Development in Young Adults Study (CARDIA)
Abstract:
OBJECTIVE ::: To examine the association of childbearing with weight and waist circumference (WC) changes, we compared women with and without pregnancies or births during follow-up. ::: ::: ::: STUDY DESIGN ::: A multicenter, longitudinal observational study over 10 years.
Comparison groups defined by the number of pregnancies and births during follow-up: P0 (0 pregnancies; nongravid), P1 (1+ miscarriages or abortions; 'short' pregnancies), B1 (1 birth), and B2 (2+ births).
Mean changes in weight and WC for P1, B1 and B2 groups vs P0 were examined separately by race (black and white), baseline parity (nulliparous and parous) and baseline weight status (normal weight; BMI <25 kg/m(2) and overweight; BMI >/=25 kg/m(2)). ::: ::: ::: SUBJECTS ::: A population-based sample of 2070 women aged 18-30 y at baseline (1053 black subjects and 1017 white subjects) from Birmingham, Alabama, Chicago, Illinois, Minneapolis, Minnesota, and Oakland, California were examined five times between 1985-1986 and 1995-1996. ::: ::: ::: MEASUREMENTS ::: Weight and WC measurements were obtained using standardized protocol at baseline and examinations at years 2, 5, 7 and 10.
Sociodemographic, reproductive, and behavioral attributes were assessed at baseline and follow-up examinations. ::: ::: ::: RESULTS ::: Gains in weight and WC associated with pregnancy and childbearing varied by race (P<0.001), baseline parity (P<0.05) and overweight status (P<0.001).
Among overweight nulliparas, excess gains in weight (black subjects: 3-5 kg, white subjects: 5-6 kg) and WC (black subjects: 3-4 cm, white subjects: 5-6 cm) were associated with 'short' pregnancies and one or more birth(s) during follow-up compared to no pregnancies (P<0.01 and 0.001).
Among normal weight nulliparas, excess gains in weight (about 1 kg) and WC (2-3 cm) were associated with follow-up birth(s) (P<0.05).
Among women parous at baseline, no excess weight gains were found, but excess WC gains (2-4 cm) were associated with follow-up births.
::: ::: ::: CONCLUSION ::: Substantial excess weight gain is associated with both short pregnancies and a first birth in women overweight prior to initiation of childbearing.
Excess weight gain was not associated with higher order births.
Increases in waist girth were cumulative with both first and higher order births among overweight as well as normal weight women.
Interventions to prevent obesity should be targeted at women who are overweight prior to initiation of childbearing.
The impact of excess WC gains associated with childbearing on women's future health risk should be evaluated further. | 16,689 |
Title:
Botulinum toxin therapy of cervical dystonia: duration of therapeutic effects
Abstract:
We sought to explore the therapeutic effect of botulinum toxin (BT) therapy by analysing the time between the BT application and the onset of its decrease (treatment duration, TD), the inter-injection interval (II), and the excess time (ET, ET = II-TD).
For this we studied 59 patients (37 females, 22 males, age 52.6 ± 10.9 years) with cervical dystonia (CD, Tsui score 9.0 ± 4.1) and BT therapy with Botox(®) and/or Xeomin(®) sequentially.
Altogether 1,289 treatment cycles were evaluated.
On average 21.8 ± 14.0 (4-66) treatment cycles were recorded for each patient.
TD was 11.8 ± 2.7 weeks (7.8 ± 1.4 to 21.0 ± 3.9 weeks), II 15.4 ± 3.4 weeks (11.3 ± 1.3 to 27.8 ± 11.6 weeks) and ET 3.5 ± 2.4 weeks (23% of II).
TD and II were stable throughout the treatment course.
In 36% of the patients we found TD ≤10 weeks, in 83% TD ≤12 weeks.
In 17% of the patients we saw treatment delays due to appointment difficulties, due to the patient's attempts to explore TD or his actual CD severity, from fear of adverse effects or due to psychiatric comorbidity.
19% of the patients showed prolonged treatment effects probably due to CD fluctuations.
0.38% of the injection series produced singular unexplained therapy failure (SUTF).
Antibody-induced therapy failure did not occur.
TD and II are stable on long-term monitoring.
SUTF, treatment delays, and CD fluctuations can occur.
23% of the time patients are treated suboptimally.
Our data suggest to reduce II.
If II is to be reduced to ≤12 weeks, use of low antigenicity BT drugs might be useful. | 16,721 |
Title:
An analysis of ophthalmology trainees’ perceptions of feedback for cataract surgery training
Abstract:
Objectives ::: To determine whether feedback for cataract surgery is perceived to be given to trainee ophthalmologists, the way in which any feedback is given, and what the trainee perceives to be the effect of feedback on their performance. | 16,805 |
Title:
First reported revascularization of complex occlusion of the right coronary artery using the IVUS-guided reverse CART technique via a gastroepiploic artery graft
Abstract:
When patients who have previously undergone coronary artery bypass graft surgery develop ischemia symptoms that cannot be controlled by optimal medical therapy, repeat revascularization is indicated.
The revascularization strategy should be based on individual clinical and anatomical characteristics.
We report here a challenging patient who presented with recurrent stable angina due to worsening of a proximal right coronary artery (RCA) stenosis to chronic total occlusion (CTO) after anastomosis of the right gastroepiploic artery (GEA) to the posterior descending artery.
A soft guidewire was advanced through the right GEA collateral channel to the distal end of the CTO, but the dedicated CTO guidewires could not be advanced across the severely calcified CTO using the retrograde wire crossing or kissing wire techniques.
The RCA was eventually revascularized by implantation of drug-eluting stents using the intravascular ultrasound-guided reverse controlled antegrade and retrograde subintimal tracking technique. | 16,823 |
Title:
Delivery of Telomerase Reverse Transcriptase Small Interfering RNA in Complex with Positively Charged Single-Walled Carbon Nanotubes Suppresses Tumor Growth
Abstract:
Purpose: To determine whether -CONH-(CH 2 ) 6 -NH 3 + Cl − functionalized single-walled carbon nanotubes (SWNT) carrying complexed small interfering RNA (siRNA) can enter into tumor cells, wherein they release the siRNA to silence the targeted gene.
Experimental Design: -CONH-(CH 2 ) 6 -NH 3 + Cl − was used to mediate the conjugation of telomerase reverse transcriptase (TERT) siRNA to SWNTs.
The ability of TERT siRNA delivered via SWNT complexes to silence the expression of TERT was assessed by their effects on the proliferation and growth of tumor cells both in vitro and in mouse models.
Results: The functionalized SWNTs -CONH-(CH 2 ) 6 -NH 3 + Cl − could facilitate the coupling of siRNAs that specifically target murine TERT expression to form the mTERT siRNA:SWNT+ complex.
These functionalized SWNTs rapidly entered three cultured murine tumor cell lines, suppressed mTERT expression, and produced growth arrest.
Injection of mTERT siRNA:SWNT+ complexes into s.c.
Lewis lung tumors reduced tumor growth.
Furthermore, human TERT siRNA:SWNT+ complexes also suppressed the growth of human HeLa cells both in vitro and when injected into tumors in nude mice.
Conclusions: -CONH-(CH 2 ) 6 -NH 3 + Cl − functionalized SWNTs carry complexed siRNA into tumor cells, wherein they release the siRNA from the nanotube sidewalls to silence the targeted gene.
The -CONH-(CH 2 ) 6 -NH 3 + Cl − functionalized SWNTs may represent a new class of molecular transporters applicable for siRNA therapeutics. | 16,898 |
Title:
Recovery of vocal fold paralysis after cardiovascular surgery
Abstract:
Objectives/Hypothesis: To review the incidence and time course of recovery of vocal fold paralysis (VFP) in adult patients after cardiovascular surgery.
Study Design: Retrospective cohort study of adults after cardiovascular surgery at a tertiary care academic medical center.
Methods: Patients with VFP after cardiovascular surgery were identified from a database of hospitalized patients undergoing voice and swallow evaluation.
VFP was confirmed using transnasal fiberoptic laryngoscopy within 1 week of surgery.
Follow-up laryngoscopy was performed in those with VFP in the outpatient clinic.
Those with persistent paralysis were followed and the time course of recovery was noted.
Results: Eighty-six adult postoperative cardiovascular surgery patients (ages 34 to 83 years, mean 68) were identified from the inpatient voice and swallowing evaluation database.
There were 20 patients (23%) with unilateral VFP.
Thirteen patients followed-up for outpatient laryngoscopy.
Ten of the thirteen patients (77%) ultimately had complete resolution of VFP.
Three patients had persistent paralysis at a mean follow-up of 18 months.
There was no obvious correlation between type of cardiovascular surgery and VFP.
Signs of recovery were generally evident prior to 6 months and no recovery was seen beyond 12 months.
Conclusions: Most patients with VFP after cardiovascular surgery recover fully.
In accordance with previous laryngeal electromyography findings, neuropraxia during cardiovascular surgery will usually recover within 6 months. | 17,014 |
Title:
Neuroendocrine responsivities of the pituitary dopamine system in male schizophrenic patients during treatment with clozapine, olanzapine, risperidone, sulpiride, or haloperidol
Abstract:
Background Atypical antipsychotic drugs, in clinical doses, occupy 5-HT2 receptors near saturation, while D2 dopamine receptors, assessed usually in striatum by SPECT or PET methods, are occupied to different degrees.
We hypothesized that these differences in D2 receptor occupancies may also be evaluated by a neuroendocrine approach, namely by measuring the plasma prolactin responses to i. m. administered haloperidol, since the expected elevations depend mainly on the free remaining D2 receptors in the tuberoinfundibular tract.
Methods We measured the plasma prolactin levels at 0, 30, 60, 90, and 120 minutes after administration of 5 mg haloperidol i. m. in six groups of male patients with schizophrenia: a) 33 patients in a drug-free state, b) 15 patients on treatment with clozapine (range 200–600 mg/day), c) 15 patients on olanzapine (10–30 mg/day), d) 14 patients on risperidone (8–16 mg/day), e) 23 patients on haloperidol (10–40 mg/day), f) 14 patients on sulpiride (600–1600 mg/day).
Data were also obtained from a group of 14 healthy male control subjects.
The differences in baseline prolactin levels and in the responses to acute haloperidol of the seven groups were compared.
Results The baseline prolactin levels did not differ significantly in the groups of controls (8.3±3.8 ng/ml), drug-free patients (8.0±3.6) and patients treated with clozapine (7.7±3.8), they were moderately elevated in patients treated with olanzapine (16.8±8.9), elevated in patients on haloperidol (34.4±17.3), and they were even higher in the groups of patients treated with risperidone (54.9±22.4) or sulpiride (58.8±27.0).
All groups of patients gave attenuated prolactin responses to i. m. haloperidol compared to healthy controls.
During treatment with haloperidol, risperidone, or sulpiride, no significant prolactin increases after i. m. haloperidol were observed.
The group treated with olanzapine gave significant prolactin increases, which were lower than those obtained in the group of patients treated with clozapine, who gave responses similar to that of the drug-free patients.
Conclusions Plasma prolactin levels and responses to i. m. haloperidol of patients on treatment with antipsychotic drugs, reflect the prolactin release potencies of the drugs, which are related, but not restricted, to their affinities to D2 dopamine receptors.
According to the prolactin baseline levels and responses to i. m. haloperidol, the drugs of this study can be categorized for their potency to the pituitary dopamine system that controls prolactin release, as follows: sulpiride > risperidone > haloperidol > olanzapine > clozapine.
This categorization is similar to that obtained by binding studies in striatal D2 dopamine receptors using brain imaging techniques. | 17,039 |
Title:
Expression of serotonin 5-HT2C receptors in GABAergic cells of the anterior raphe nuclei
Abstract:
We have used double in situ hybridization to examine the cellular localization of 5-HT2C receptor mRNA in relation to serotonergic and GABAergic neurons in the anterior raphe nuclei of the rat.
In the dorsal and median raphe nuclei 5-HT2C receptor mRNA was not detected in serotonergic cells identified as those expressing serotonin (5-HT) transporter mRNA.
In contrast, 5-HT2C receptor mRNA was found in most GABAergic cells, recognized by the presence of glutamic acid decarboxylase mRNA.
Such 5-HT2C receptor-positive GABAergic neurons were mainly located in the intermediolateral and lateral portions of the dorsal raphe and lateral part of the median raphe.
The present data give anatomical support to a previous hypothesis that proposed a negative-feedback loop involving reciprocal connections between GABAergic interneurons bearing 5-HT2A/2C receptors and 5-HT neurons in the dorsal raphe and surrounding areas.
According to this model, the excitation of GABAergic interneurons through these 5-HT2C (and also 5-HT2A) receptors would result in the suppression of 5-HT cell firing. | 17,082 |
Title:
Enhanced recognition of protein transmembrane domains with prediction-based structural profiles
Abstract:
Motivation: Membrane domain prediction has recently been re-evaluated by several groups, suggesting that the accuracy of existing methods is still rather limited.
In this work, we revisit this problem and propose novel methods for prediction of alpha-helical as well as beta-sheet transmembrane (TM) domains.
The new approach is based on a compact representation of an amino acid residue and its environment, which consists of predicted solvent accessibility and secondary structure of each amino acid.
A recently introduced method for solvent accessibility prediction trained on a set of soluble proteins is used here to indicate segments of residues that are predicted not to be accessible to water and, therefore, may be 'buried' in the membrane.
While evolutionary profiles in the form of a multiple alignment are used to derive these simple 'structural profiles', they are not used explicitly for the membrane domain prediction and the overall number of parameters in the model is significantly reduced.
This offers the possibility of a more reliable estimation of the free parameters in the model with a limited number of experimentally resolved membrane protein structures. ::: ::: Results: Using cross-validated training on available sets of structurally resolved and non-redundant alpha and beta membrane proteins, we demonstrate that membrane domain prediction methods based on such a compact representation outperform approaches that utilize explicitly evolutionary profiles and multiple alignments.
Moreover, using an external evaluation by the TMH Benchmark server we show that our final prediction protocol for the TM helix prediction is competitive with the state-of-the-art methods, achieving per-residue accuracy of ∼89% and per-segment accuracy of ∼80% on the set of high resolution structures used by the TMH Benchmark server.
At the same time the observed rates of confusion with signal peptides and globular proteins are the lowest among the tested methods.
The new method is available online at http://minnou.cchmc.org. ::: ::: Contact: [email protected] ::: ::: Supplementary information: Supplementary data are available at Bioinformatics online and at http://minnou.cchmc.org/cao_et_al_supplementary_materials.pdf | 17,089 |
Title:
Continuous Stroke Unit Electrocardiographic Monitoring Versus 24-Hour Holter Electrocardiography for Detection of Paroxysmal Atrial Fibrillation After Stroke
Abstract:
BACKGROUND AND PURPOSE ::: Cardioembolism in paroxysmal atrial fibrillation (pxAF) is a frequent cause of ischemic stroke.
Sensitive detection of pxAF after stroke is crucial for adequate secondary stroke prevention; the optimal diagnostic modality to detect pxAF on stroke units is unknown.
We compared 24-hour Holter electrocardiography (ECG) with continuous stroke unit ECG monitoring (CEM) for pxAF detection. ::: ::: ::: METHODS ::: Patients with acute ischemic stroke or transient ischemic attack were prospectively enrolled.
After a 12-channel ECG on admission, all patients received 24-hour Holter ECG and CEM.
Additionally, ECG monitoring data underwent automated analysis using dedicated software to identify pxAF.
Patients with a history of atrial fibrillation or with atrial fibrillation on the admission ECG were excluded. ::: ::: ::: RESULTS ::: Four hundred ninety-six patients (median age, 69 years; 61.5% male) fulfilled all inclusion criteria (ischemic stroke: 80.4%; transient ischemic attack: 19.6%).
Median stroke unit stay lasted 88.8 hours (interquartile range, 65.0-122.0).
ECG data for automated CEM analysis were available for a median time of 64.0 hours (43.0-89.8).
Paroxysmal AF was documented in 41 of 496 patients (8.3%).
Of these, Holter detected pxAF in 34.1%; CEM in 65.9%; and automated CEM in 92.7%.
CEM and automated CEM detected significantly more patients with pxAF than Holter (P<0.001), and automated CEM detected more patients than CEM (P<0.001). ::: ::: ::: CONCLUSIONS ::: Automated analysis of CEM improves pxAF detection in patients with stroke on stroke units compared with 24-hour Holter ECG.
The comparative usefulness of prolonged or repetitive Holter ECG recordings requires further evaluation. | 17,100 |
Title:
Three-dimensional reconstruction of the antennal lobe inDrosophila melanogaster
Abstract:
We present the first three-dimensional map of the antennal lobe of Drosophila melanogaster, based on confocal microscopic analysis of glomeruli stained with the neuropil-specific monoclonal antibody nc82.
The analysis of confocal stacks allowed us to identify glomeruli according to the criteria shape, size, position, and intensity of antibody labeling.
Forty glomeruli were labeled by nc82, eight of which have not been described before.
Three glomeruli previously shown exclusively by backfills were not discernible in nc82 stainings.
We distinguish three classes of glomeruli: (1) ‘‘landmark’’ glomeruli that are constant in all four criteria mentioned above, (2) less well-demarcated glomeruli that deviate in a single criterion, and (3) poorly defined glomeruli that vary in more than one criterion.
All class 2 and 3 glomeruli can be identified by comparison with landmark neighbors.
To further aid identification, our model assigns glomeruli to five arrays, each of which is defined by a prominent landmark glomerulus.
Six glomeruli consist of distinct, but contiguous structural units, termed ‘‘compartments.
’’ Glomerular variability observed occasionally between males and females is in the same range as between individuals of the same sex, suggesting the lack of a significant sexual dimorphism in the glomerular pattern.
We compare the new model with a previous map and address its potential for mapping activity and expression patterns.
An important goal of this work was to create three-dimensional reference models of the antennal lobe, which are accessible on-line.
J. Comp.
Neurol.
405:543‐552, 1999.
r 1999 Wiley-Liss, Inc. Indexing terms: olfactory system; glomeruli; confocal microscopy; enhancer trap lines; rendering; VRML | 17,106 |
Title:
Indoor concentrations of nicotine in low-income, multi-unit housing: associations with smoking behaviours and housing characteristics
Abstract:
Objective: An analysis of airborne nicotine measurements collected in 49 low-income, multi-unit residences across the Greater Boston Area.
Methods: Nicotine concentrations were determined using passive monitors placed in homes over a one-week sampling period and air exchange rates (AER) were sampled using the perfluorocarbon tracer technique.
Residents were surveyed through a questionnaire about smoking behaviour and a visual inspection was conducted to collect information on housing characteristics contributing to secondhand smoke (SHS) exposure.
Using a mass balance model to account for the air exchange rate, volume of the home and sorption and re-emission of nicotine on indoor surfaces, the effective smoking rate (SR eff ) was determined for each residence.
Results: Nicotine levels ranged from the limit of detection to 26.92 μg/m 3 , with a mean of 2.20 μg/m 3 and median of 0.13 μg/m 3 .
Nicotine measurements were significantly associated with the number of smokers in the household and the number of cigarettes smoked in the home.
The results of this study suggest that questionnaire reports can provide a valid estimate of residential exposure to tobacco smoke.
In addition, this study found evidence that tobacco smoke contamination in low-income housing developments is not limited to homes with smokers (either residing in the home or visiting).
The frequent report of tobacco smoke odour coming from other apartments or hallways resulted in increased levels of nicotine concentrations and SR eff in non-smoking homes, suggestive of SHS infiltration from neighbouring units.
Conclusion: These findings have important implications for smoking regulations in multi-unit homes and highlight the need to reduce involuntary exposure to tobacco smoke among low-income housing residents. | 17,107 |
Title:
Exploring the Role of Cognitive Reserve in Early-Onset Dementia
Abstract:
Aim: Cognitive reserve (CR) is important in protecting the brain from injury and has not been investigated in people with early-onset dementia (EOD).
Methods: A retrospective case control study of 44 patients with dementia onset prior to 65 years of age: Alzheimer’s disease (AD) = 23; frontotemporal dementia (FTD) = 21.
Groups were matched for age, education, Mini-Mental State Examination (MMSE), premorbid IQ, sex and APOE e4 genotype.
Years of formal education were used as a marker of CR.
Relationships between education and neuropsychological data was examined using linear regression analyses.
Results: There were no demographic differences between the AD and FTD groups.
Significant associations were found between education and attention, working memory and visuospatial abilities.
There was an effect of CR for the EOD group and selective effects in FTD and AD.
Conclusion: Our findings suggest CR is operational in patients with FTD and AD. | 17,258 |
Title:
BAC library resources for map-based cloning and physical map construction in barley (Hordeum vulgare L.)
Abstract:
BackgroundAlthough second generation sequencing (2GS) technologies allow re-sequencing of previously gold-standard-sequenced genomes, whole genome shotgun sequencing and de novo assembly of large and complex eukaryotic genomes is still difficult.
Availability of a genome-wide physical map is therefore still a prerequisite for whole genome sequencing for genomes like barley.
To start such an endeavor, large insert genomic libraries, i.e. Bacterial Artificial Chromosome (BAC) libraries, which are unbiased and representing deep haploid genome coverage, need to be ready in place.
ResultFive new BAC libraries were constructed for barley (Hordeum vulgare L.) cultivar Morex.
These libraries were constructed in different cloning sites (Hind III, EcoR I, Mbo I and BstX I) of the respective vectors.
In order to enhance unbiased genome representation and to minimize the number of gaps between BAC contigs, which are often due to uneven distribution of restriction sites, a mechanically sheared library was also generated.
The new BAC libraries were fully characterized in depth by scrutinizing the major quality parameters such as average insert size, degree of contamination (plate wide, neighboring, and chloroplast), empty wells and off-scale clones (clones with <30 or >250 fragments).
Additionally a set of gene-based probes were hybridized to high density BAC filters and showed that genome coverage of each library is between 2.4 and 6.6 X.ConclusionBAC libraries representing >20 haploid genomes are available as a new resource to the barley research community.
Systematic utilization of these libraries in high-throughput BAC fingerprinting should allow developing a genome-wide physical map for the barley genome, which will be instrumental for map-based gene isolation and genome sequencing. | 17,292 |
Title:
Mapping of mutations affecting synthesis of exocellular enzymes in Bacillus subtilis
Abstract:
The sacUh, amyB and pap mutations are identical with respect to their pleiotropic phenotype and their genetic location.
Strains bearing these mutations overproduce several exocellular enzymes: alpha amylase, lavansucrase and proteases, they are poorly or not at all transformable and most of them are devoid of flagella.
These mutations are tightly linked to the sacU- mutations by transformation and therefore lie between the hisA1 and gtaB290 markers.
It is possible that the sacUh, amyB and pap mutations on one hand and the sacU- mutations on the other are two different classes of alterations of the same regulatory gene controlling the synthesis of some exocellular enzymes and several other cellular functions.
Furthermore an amy- mutation, leading to the lack of alpha-amylase activity, was mapped between the lin2 and aroI906 markers which are not linked to the sacU locus. | 17,393 |
Title:
The Plights of African Resources Patenting through the Lenses of the World Trade Organisation: An Assessment of South Africa’s Rooibos Tea’s Labyrith Journey
Abstract:
BACKGROUND ::: Just as developing states are blessed with natural resources capable of transforming their economies into a positive direction, the imposed World Trade Organisation's (WTO) mores continue to relegate them to the status of underdevelopment.
The consequences of this on investment, trade and finance in Third World States (TWSs), especially Africa, are disarticulation of the economy, exploitation, disinvestment, unemployment, political instability and unavailability of relevant technology to move TWSs forward, among others.
This gives rise to the politics behind Rooibos (Aspalathus linearis) patenting (a medicinal plant found only in South Africa) by various multinational corporations (MNCs). ::: ::: ::: MATERIALS AND METHODS ::: This study adopted political economy approach with emphasis on both primary and secondary sources of data collection using content analysis. ::: ::: ::: RESULT ::: There is need to adhere strictly to the issues of intellectual property rights (IPRs), geographical indications (GIs), prior informed consent (PIC), and access and sharing benefits (ASB).
These have not been observed by the western states because of their economic of neo-imperialism to the disadvantage of developing states.
::: ::: ::: CONCLUSION ::: This paper recommends that there is need for a regional regime such as African Regional Intellectual Property Organisation (ARIPO), on indigenous knowledge (IK) to patent the continental biodiversity resources. | 17,454 |
Title:
Optimising the analysis of transcript data using high density oligonucleotide arrays and genomic DNA-based probe selection
Abstract:
BackgroundAffymetrix GeneChip arrays are widely used for transcriptomic studies in a diverse range of species.
Each gene is represented on a GeneChip array by a probe-set, consisting of up to 16 probe-pairs.
Signal intensities across probe-pairs within a probe-set vary in part due to different physical hybridisation characteristics of individual probes with their target labelled transcripts.
We have previously developed a technique to study the transcriptomes of heterologous species based on hybridising genomic DNA (gDNA) to a GeneChip array designed for a different species, and subsequently using only those probes with good homology.
ResultsHere we have investigated the effects of hybridising homologous species gDNA to study the transcriptomes of species for which the arrays have been designed.
Genomic DNA from Arabidopsis thaliana and rice (Oryza sativa) were hybridised to the Affymetrix Arabidopsis ATH1 and Rice Genome GeneChip arrays respectively.
Probe selection based on gDNA hybridisation intensity increased the number of genes identified as significantly differentially expressed in two published studies of Arabidopsis development, and optimised the analysis of technical replicates obtained from pooled samples of RNA from rice.
ConclusionThis mixed physical and bioinformatics approach can be used to optimise estimates of gene expression when using GeneChip arrays. | 17,462 |
Title:
Effect of Endotoxin on P-Glycoprotein-Mediated Biliary and Renal Excretion of Rhodamine-123 in Rats
Abstract:
The effects of Klebsiella pneumoniae endotoxin on the biliary excretion and renal handling of rhodamine-123 were investigated in rats at different times after intraperitoneal injection (1 mg/kg of body weight).
The typical substrates for P glycoprotein, i.e., cyclosporine, colchicine, and erythromycin, inhibited the biliary clearance of rhodamine-123, whereas a substrate for organic cation transporter, cimetidine, did not inhibit clearance, suggesting that rhodamine-123 is transported mainly by P glycoprotein.
The biliary, renal, and tubular secretory clearances of rhodamine-123 and the glomerular filtration rate significantly decreased 6 h after injection of endotoxin but returned to control levels by 24 h. These results suggest that endotoxin-induced decreases in P-glycoprotein-mediated biliary excretion and renal handling of rhodamine-123 were probably due to impairment of P-glycoprotein-mediated transport ability.
Pretreatment with pentoxifylline (50 mg/kg) significantly inhibited endotoxin-induced increases in tumor necrosis factor alpha (TNF-) levels in plasma, which ameliorated the endotoxin-induced reduction of the biliary excretion of rhodamine-123.
It is likely that endotoxin-induced impairment of the transport of rhodamine-123 is caused, in part, by overproduction of TNF-.
The effect of endotoxin on the expression of P-glycoprotein mRNA in liver and kidneys of rats was investigated by using a reverse transcriptase PCR.
The expression of Mdr1a mRNA in both liver and kidney decreased 6 h after endotoxin injection and returned to control levels after 24 h, whereas the expression of Mdr1b mRNA in liver increased at both times and that in kidney decreased at 24 h. These findings suggest that K. pneumoniae endotoxin dramatically decreases P-glycoprotein-mediated biliary and renal excretion of rhodamine-123 probably by decreasing the expression of Mdr1a, which is likely due to increased plasma TNFlevels. | 17,802 |
Title:
Polarisation Dynamics of Vector Soliton Molecules in Mode Locked Fibre Laser
Abstract:
Two fundamental laser physics phenomena - dissipative soliton and polarisation of light are recently merged to the concept of vector dissipative soliton (VDS), viz. train of short pulses with specific state of polarisation (SOP) and shape defined by an interplay between anisotropy, gain/loss, dispersion, and nonlinearity.
Emergence of VDSs is both of the fundamental scientific interest and is also a promising technique for control of dynamic SOPs important for numerous applications from nano-optics to high capacity fibre optic communications.
Using specially designed and developed fast polarimeter, we present here the first experimental results on SOP evolution of vector soliton molecules with periodic polarisation switching between two and three SOPs and superposition of polarisation switching with SOP precessing.
The underlying physics presents an interplay between linear and circular birefringence of a laser cavity along with light induced anisotropy caused by polarisation hole burning. | 17,905 |
Title:
Heat shock proteins – modulators of apoptosis in tumour cells
Abstract:
Apoptosis is a genetically programmed, physiological method of cell destruction.
A variety of genes are now recognised as positive or negative regulators of this process.
Expression of inducible heat shock proteins (hsp) is known to correlate with increased resistance to apoptosis induced by a range of diverse cytotoxic agents and has been implicated in chemotherapeutic resistance of tumours and carcinogenesis.
Intensive research on apoptosis over the past number of years has provided significant insights into the mechanisms and molecular events that occur during this process.
The modulatory effects of hsps on apoptosis are well documented, however, the mechanisms of hsp-mediated protection against apoptosis remain to be fully defined, although several hypotheses have been proposed.
Elucidation of these mechanisms should reveal novel targets for manipulating the sensitivity of leukaemic cells to therapy.
This review aims to explain the currently understood process of apoptosis and the effects of hsps on this process.
Several proposed mechanisms for hsp protection against apoptosis and the therapeutic implications of hsps in leukaemia are also discussed. | 17,914 |
Title:
Sparsey™: event recognition via deep hierarchical sparse distributed codes
Abstract:
The visual cortex’s hierarchical, multi-level organization is captured in many biologically inspired computational vision models, the general idea being that progressively larger scale (spatially/temporally) and more complex visual features are represented in progressively higher areas.
However, most earlier models use localist representations (codes) in each representational field (which we equate with the cortical macrocolumn, “mac”), at each level.
In localism, each represented feature/concept/event (hereinafter “item”) is coded by a single unit.
The model we describe, Sparsey, is hierarchical as well but crucially, it uses sparse distributed coding (SDC) in every mac in all levels.
In SDC, each represented item is coded by a small subset of the mac’s units.
The SDCs of different items can overlap and the size of overlap between items can be used to represent their similarity.
The difference between localism and SDC is crucial because SDC allows the two essential operations of associative memory, storing a new item and retrieving the best-matching stored item, to be done in fixed time for the life of the model.
Since the model’s core algorithm, which does both storage and retrieval (inference), makes a single pass over all macs on each time step, the overall model’s storage/retrieval operation is also fixed-time, a criterion we consider essential for scalability to the huge (“Big Data”) problems.
A 2010 paper described a non-hierarchical version of this model in the context of purely spatial pattern processing.
Here, we elaborate a fully hierarchical model (arbitrary numbers of levels and macs per level), describing novel model principles like progressive critical periods, dynamic modulation of principal cells’ activation functions based on a mac-level familiarity measure, representation of multiple simultaneously active hypotheses, a novel method of time warp invariant recognition, and we report results showing learning/recognition of spatiotemporal patterns. | 17,997 |
Title:
The anomalous Kentucky coffeetree: megafaunal fruit sinking to extinction?
Abstract:
The Kentucky coffeetree (Gymnocladus dioicus, Fabaceae) is an ecological paradox.
A rare tree in nature in eastern and central North America, G. dioicus produces legumes that are only known to be dispersed by water, but appear similar to fruits consumed and dispersed by elephants and rhinoceros.
One would expect the pods to be consumed by livestock, but the pulp and seeds are toxic to cattle and sheep.
We examine the puzzle of G. dioicus dispersal in light of its other reproductive and life history characteristics and find that it probably is a botanical anachronism, in terms of both a set of dispersal agents long extinct and habitats, including what we term megafaunal disclimaxes, which have disappeared.
Large seeds, the megafaunal gestault of the fruit, a dioecious mating system, and shade-intolerance combined with vigorous cloning suggest a widely dispersed pioneer of Miocene through Pleistocene habitats profoundly altered by large-mammal herbivory.
As to what ate it, we can only say there were once many candidates.
We hypothesize that the plant is an ecological anachronism, sinking to extinction in the wild. | 18,015 |
Title:
Matrix metalloproteinases in type 2 diabetes and non-diabetic controls: effects of short-term and chronic hyperglycaemia
Abstract:
Introduction ::: The role of matrix metalloproteinases (MMPs) in type 2 diabetes mellitus (DM) is not clear as increased activation of MMPs in the vasculature contrasts with decreased activity of MMPs in the kidneys, contributing to development of nephropathy. | 18,063 |
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