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Title:
Treatment of patients with malignant lymphomas with monoclonal antibodies
Abstract:
Malignant lymphomas represent a heterogenous group of B and T cell-derived malignancies.
Most lymphomas are sensitive to chemo- and radiotherapy, however many patients will eventually relapse.
Immunotherapeutic approaches including monoclonal antibodies, cytokines or vaccination approaches may offer an alternative treatment of chemotherapy-resistant residual cells especially in cases with low tumor burden or residual disease following chemo- or radiotherapy.
Monoclonal antibodies have been successfully applied in their native form, or coupled with radioisotopes or toxins to selectively destroy lymphoma cells and promising results in early clinical trials have been obtained.
Alternatively, bispecific antibodies and idiotypic vaccination strategies are used to target autologous T cells to eliminate lymphoma cells.
A humanized anti-CD20 antibody showed excellent results in chemotherapy refractory lymphomas and has recently been approved for clinical application in CD20 positive B cell lymphomas.
Bone Marrow Transplantation (2000) 25, Suppl. 2, S50–S53. | 18,112 |
Title:
Dopamine D4 Receptor Activation Inhibits Presynaptically Glutamatergic Neurotransmission in the Rat Supraoptic Nucleus
Abstract:
Oxytocin and vasopressin release from magnocellular neurons of the supraoptic nucleus is under the control of glutamate-dependent excitation.
The supraoptic nucleus also receives a generalized dopaminergic input from hypothalamic sources.
To determine if dopamine can influence this excitatory drive onto the magnocellular neurons, we used whole-cell patch clamp to record the effect of dopamine on evoked and miniature excitatory postsynaptic currents in rat hypothalamic slices.
Dopamine exposure (30 μM to 1 mM) induced a large and reversible reduction in the amplitude of evoked excitatory postsynaptic current in nearly all magnocellular cells tested.
D4 receptors appeared to mediate dopamine's activity, based on inhibition of the response with 50 μM clozapine, but not by SCH 23390 or sulpiride, and mimicry of dopamine's action with the D4 specific agonist, PD 168077.
Analysis of paired-pulse experiments and miniature postsynaptic currents indicated that dopamine's action involved a presynaptic mechanism, since the frequency of miniature postsynaptic currents was reduced with dopamine exposure without any change in current kinetics or amplitude, while the paired-pulse ratio increased.
We therefore have demonstrated for the first time a role for dopamine D4 receptors in the supraoptic nucleus in the presynaptic inhibition of glutamatergic neurotransmission onto magnocellular neurons. | 18,135 |
Title:
Modulation of the cell cycle-dependent cytotoxicity of adriamycin and 4-hydroperoxycyclophosphamide by novobiocin, an inhibitor of mammalian topoisomerase II.
Abstract:
Centrifugal elutriation was used to obtain synchronized cell populations in various cell cycle phases without prior growth-perturbing manipulation.
Treatment of these subpopulations with novobiocin (NOVO), a putative inhibitor of the mammalian topoisomerase II enzyme, revealed a unique cell cycle phase-dependent cytotoxicity for this agent.
At a concentration of 0.3 mM, NOVO was cytotoxic only to a specific cell subpopulation in the G1-S phase boundary.
Cells in other cell cycle phases were completely unaffected.
Additionally, S and G2M phase cells progressed through the cell cycle relatively unaffected by NOVO but were blocked at the G1-S boundary.
NOVO treatment protected tumor cells from Adriamycin (ADR)-induced lethality but sensitized them to the toxic action of 4-hydroperoxycyclophosphamide, and alkylating agent.
These opposing effects of NOVO were demonstrated in all of the four tumor cell lines investigated: A431 and HEp3 (derived from human squamous cell carcinomas); MLS, a human ovarian cancer cell line; and a Chinese hamster ovary cell line.
The degree of protection against ADR was the greatest for S-phase cells, intermediate for cells in early G1 and M phases, and the least for late G1 cells.
This cell cycle-dependent protection by NOVO, which is identical to the cell cycle-dependent cytotoxicity of ADR, was consistent with the idea that NOVO interfered directly with the cell-killing mechanism of ADR.
In contrast, even though the cytotoxic activity of 4-hydroperoxycyclophosphamide exhibited significant cell cycle dependency, NOVO enhanced 4-hydroperoxycyclophosphamide lethality equally for all cell cycle phases. | 18,154 |
Title:
Methionine-dependence phenotype in the de novo pathway in BRCA1 and BRCA2 mutation carriers with and without breast cancer.
Abstract:
Methionine-dependence phenotype (MDP) refers to the reduced ability of cells to proliferate when methionine is restricted and/or replaced by its immediate precursor homocysteine.
MDP is a characteristic of human tumors in vivo, human tumor cell lines, and normal somatic tissue in some individuals.
It was hypothesized that MDP is a risk factor for developing breast cancer in BRCA (BRCA1 and BRCA2) germline mutation carriers.
To test the hypothesis, human peripheral blood lymphocytes of BRCA carriers with and without breast cancer and healthy non-carrier relatives (controls) were cultured for 9 days in medium containing either 0.1 mmol/L L-methionine or 0.2 mmol/L D,L-homocysteine, with the ratio of viable cell growth in both types of medium after 9 days used to calculate the methionine-dependence index (MDI), a measure of MDP.
We also tested whether MDP was associated with common polymorphisms in methionine metabolism.
Viable cell growth, MDI, and polymorphism frequency in MTRR (A66G and C524T) and MTHFR (A1298C and A1793G) did not differ among the study groups; however, MDI tended to be higher in BRCA carriers with breast cancer than those without and was significantly increased in MTHFR 677T allele carriers relative to wild-type carriers (P=0.017).
The presence of MTR A2756G mutant allele and MTHFR C677T mutant allele in carriers was associated with increased breast cancer risk [odds ration, 3.2 (P=0.16; 95% confidence interval, 0.76-13.9) and 3.9 (P=0.09; 95% confidence interval, 0.93-16.3), respectively].
The results of this study support the hypothesis that defects in methionine metabolism may be associated with breast cancer risk in BRCA carriers. | 18,247 |
Title:
Schizophrenia as a self-disorder due to perceptual incoherence
Abstract:
Abstract The aim of this review is to describe the potential relationship between multisensory disintegration and self-disorders in schizophrenia spectrum disorders.
Sensory processing impairments affecting multisensory integration have been demonstrated in schizophrenia.
From a developmental perspective multisensory integration is considered to be crucial for normal self-experience.
An impairment of multisensory integration is called ‘perceptual incoherence’.
We theorize that perceptual incoherence may evoke incoherent self-experiences including depersonalization, ambivalence, diminished sense of agency, and ‘loosening of associations’ between thoughts, feelings and actions that lie within the framework of ‘self-disorders’ as described by Sass and Parnas (2003) .
We postulate that subconscious attempts to restore perceptual coherence may induce hallucinations and delusions.
Increased insight into mechanisms underlying ‘self-disorders’ may enhance our understanding of schizophrenia, improve recognition of early psychosis, and extend the range of therapeutic possibilities. | 18,256 |
Title:
Spatial location and its relevance for terminological inferences in bio-ontologies
Abstract:
An adequate and expressive ontological representation of biological organisms and their parts requires formal reasoning mechanisms for their relations of physical aggregation and containment.
We demonstrate that the proposed formalism allows to deal consistently with "role propagation along non-taxonomic hierarchies", a problem which had repeatedly been identified as an intricate reasoning problem in biomedical ontologies.
The proposed approach seems to be suitable for the redesign of compositional hierarchies in (bio)medical terminology systems which are embedded into the framework of the OBO (Open Biological Ontologies) Relation Ontology and are using knowledge representation languages developed by the Semantic Web community. | 18,300 |
Title:
PCR-Based Detection of Toxoplasma gondii DNA in Blood and Ocular Samples for Diagnosis of Ocular Toxoplasmosis
Abstract:
PCR detection of Toxoplasma gondii in blood has been suggested as a possibly efficient method for the diagnosis of ocular toxoplasmosis (OT) and furthermore for genotyping the strain involved in the disease.
To assess this hypothesis, we performed PCR with 121 peripheral blood samples from 104 patients showing clinical and/or biological evidence of ocular toxoplasmosis and from 284 (258 patients) controls.
We tested 2 different extraction protocols, using either 200 μl (small volume) or 2 ml (large volume) of whole blood.
Sensitivity was poor, i.e., 4.1% and 25% for the small- and large-volume extractions, respectively.
In comparison, PCR with ocular samples yielded 35.9% sensitivity, while immunoblotting and calculation of the Goldmann-Witmer coefficient yielded 47.6% and 72.3% sensitivities, respectively.
Performing these three methods together provided 89.4% sensitivity.
Whatever the origin of the sample (ocular or blood), PCR provided higher sensitivity for immunocompromised patients than for their immunocompetent counterparts.
Consequently, PCR detection of Toxoplasma gondii in blood samples cannot currently be considered a sufficient tool for the diagnosis of OT, and ocular sampling remains necessary for the biological diagnosis of OT. | 18,422 |
Title:
Clustering by Fuzzy Neural Gas and Evaluation of Fuzzy Clusters
Abstract:
We consider some modifications of the neural gas algorithm.
First, fuzzy assignments as known from fuzzy c-means and neighborhood cooperativeness as known from self-organizing maps and neural gas are combined to obtain a basic Fuzzy Neural Gas.
Further, a kernel variant and a simulated annealing approach are derived.
Finally, we introduce a fuzzy extension of the ConnIndex to obtain an evaluation measure for clusterings based on fuzzy vector quantization. | 18,468 |
Title:
Consumer Reactions to Differing Amounts of Written Drug Information
Abstract:
Four prototype patient package inserts (PPIs) for erythromycin were tested in an analog study using 325 individuals drawn from a college community.
There was no difference in the total amount of knowledge communicated by the different PPIs, but results for individual test items suggest (1) that more explicit information may be better recalled, and (2) that longer PPIs may aid in information integration, whereas shorter PPIs may aid in pure recall of facts.
PPIs containing elaboration on why drug effects occur were rated by the subjects as more "accurate." Subjects tended to rate PPIs that provided behavioral instructions on what to do if certain drug effects occurred as designed to promote better care. | 18,483 |
Title:
Permanent myopathy caused by mutation of SCN4A Metl592Val: Observation on myogenesis in vitro and on effect of basic fibroblast growth factor on the muscle
Abstract:
Objective ::: The present study is to observe in vitro the proliferation ability of the muscle cells from permanent myopathy (PM) patients of nomokalaemic periodic paralysis (normKPP), which is caused by mutations of Met1592Val in the skeletal muscle voltage gated sodium channel (SCN4A) gene on chromosome 17q23.1.
We also evaluate the possible effect of the foreign basic fibroblast growth factor (bFGF) in preventing and curing PM. | 18,502 |
Title:
High molecular weight-multicatalytic proteinases in premature and mature oocytes of Rana pipiens
Abstract:
High molecular weight, multicatalytic proteinases (named proteasomes) have been for the first time found, on the basis of different protein patterns, in the cytoplasmic soluble fractions of both non-hormone-treated (premature) and progesterone-treated (mature) oocytes of a frog (Rana pipiens). | 18,617 |
Title:
The DNA Methylome of Human Peripheral Blood Mononuclear Cells
Abstract:
DNA methylation plays an important role in biological processes in human health and disease.
Recent technological advances allow unbiased whole-genome DNA methylation (methylome) analysis to be carried out on human cells.
Using whole-genome bisulfite sequencing at 24.7-fold coverage (12.3-fold per strand), we report a comprehensive (92.62%) methylome and analysis of the unique sequences in human peripheral blood mononuclear cells (PBMC) from the same Asian individual whose genome was deciphered in the YH project.
PBMC constitute an important source for clinical blood tests world-wide.
We found that 68.4% of CpG sites and <0.2% of non-CpG sites were methylated, demonstrating that non-CpG cytosine methylation is minor in human PBMC.
Analysis of the PBMC methylome revealed a rich epigenomic landscape for 20 distinct genomic features, including regulatory, protein-coding, non-coding, RNA-coding, and repeat sequences.
Integration of our methylome data with the YH genome sequence enabled a first comprehensive assessment of allele-specific methylation (ASM) between the two haploid methylomes of any individual and allowed the identification of 599 haploid differentially methylated regions (hDMRs) covering 287 genes.
Of these, 76 genes had hDMRs within 2 kb of their transcriptional start sites of which >80% displayed allele-specific expression (ASE).
These data demonstrate that ASM is a recurrent phenomenon and is highly correlated with ASE in human PBMCs.
Together with recently reported similar studies, our study provides a comprehensive resource for future epigenomic research and confirms new sequencing technology as a paradigm for large-scale epigenomics studies. | 18,670 |
Title:
Using no-cost mobile phone reminders to improve attendance for HIV test results: a pilot study in rural Swaziland
Abstract:
Mobile technology has great potential to improve adherence and treatment outcomes in healthcare settings.
However, text messaging and phone calls are unaffordable in many resource-limited areas.
This study investigates the use of a no-cost alternative mobile phone technology using missed calls (‘buzzing’) to act as a patient reminder.
The use of missed calls as a patient reminder was evaluated for feasibility and effectiveness as an appointment reminder in the follow-up of newly-diagnosed human immunodeficiency virus (HIV) positive patients in an HIV testing and counselling department in rural Swaziland.
This pilot study uses a before-and-after operational research study design, with all patients with mobile phones being offered the intervention.
The primary outcome was the rate of attendance at the HIV testing and counselling department for collection of results in those with mobile phones before and after the introduction of the intervention.
Over two-thirds, 71.8% (459/639), of patients had a mobile phone.
All patients with a mobile phone consented to being buzzed.
There was no difference in attendance for follow-up at the clinic before and after the intervention was implemented (80.1% versus 83.3%, p = 0.401), or after adjusting for confounding factors (OR 1.13, p = 0.662).
This pilot study illustrates that mobile technology may be feasible in rural, resource-poor settings as there are high rates of mobile phone ownership and the intervention had a 100% uptake rate, with positive feedback from staff and patients.
In this particular setting, the intervention did not improve attendance rates.
However, further research is planned to investigate the impact on adherence to appointments and medications in other settings, such as HIV chronic care follow-up and as part of an enhanced package to improve adherence. | 18,729 |
Title:
RL: A simulation test bed for hypotheses of genome evolution
Abstract:
Motivation: Microbial genomes undergo evolutionary processes such as gene family expansion and contraction, variable rates and patterns of sequence substitution and lateral genetic transfer.
Simulation tools are essential for both the generation of data under different evolutionary models and the validation of analytical methods on such data.
However, meaningful investigation of phenomena such as lateral genetic transfer requires the simultaneous consideration of many underlying evolutionary processes.
::: ::: Results: We have developed EvolSimulator, a software package that combines non-stationary sequence and gene family evolution together with models of lateral genetic transfer, within a customizable birth–death model of speciation and extinction.
Here, we examine simulated data sets generated with EvolSimulator using existing statistical techniques from the evolutionary literature, showing in detail each component of the simulation strategy. ::: ::: Availability: Source code, manual and other information are freely available at www.bioinformatics.org.au/evolsim ::: ::: Contact: [email protected] ::: ::: Supplementary information: Supplementary data are available at Bioinformatics online. | 18,779 |
Title:
The role of the cell cycle and cytokinesis in regulating neuroblast sublineage gene expression in the Drosophila CNS
Abstract:
The precise temporal control of gene expression is critical for specifying neuronal identity in the Drosophila central nervous system (CNS).
A particularly interesting class of genes are those expressed at stereotyped times during the cell lineage of identified neural precursors (neuroblasts): these are termed ‘sublineage’ genes.
Although sublineage gene function is vital for CNS development, the temporal regulation of this class of genes has not been studied.
Here we show that four genes (ming, even-skipped, unplugged and achaete) are expressed in specific neuroblast sublineages.
We show that these neuroblasts can be identified in embryos lacking both neuroblast cytokinesis and cell cycle progression (string mutants) and in embryos lacking only neuroblast cytokinesis (pebble mutants).
We find that the unplugged and achaete genes are expressed normally in string and pebble mutant embryos, indicating that temporal control is independent of neuroblast cytokinesis or counting cell cycles.
In contrast, neuroblasts require cytokinesis to activate sublineage ming expression, while a single, identified neuroblast requires cell cycle progression to activate even-skipped expression.
These results suggest that neuroblasts have an intrinsic gene regulatory hierarchy controlling unplugged and achaete expression, but that cell cycle- or cytokinesis-dependent mechanisms are required for ming and eve CNS expression.
SUMMARY | 18,807 |
Title:
Ritual Risk: Incense Use and Cardiovascular Mortality
Abstract:
Numerous studies have examined exposures to indoor combustion products such as secondhand smoke and emissions from burning of solid fuels.
However, only a few have examined incense burning as a potential health threat, even though incense is commonly used for religious and ritual purposes in China, Taiwan, Singapore, India, and Middle Eastern nations.1,2 In this issue of EHP, investigators report an association between long-term incense use and increased cardiovascular mortality.1 ::: ::: ::: ::: Although the ritual use of incense is common around the world, few studies have investigated its impact on indoor air quality and human health. ::: ::: ::: ::: The study used data from the Singapore Chinese Health Study, which enrolled a cohort of 63,257 Chinese adults aged 45–74 years between 1993 and 1998.
The authors identified cardiovascular deaths of cohort members via a nationwide death registry, checking the registry yearly through 31 December 2011.
They stratified their analysis for factors such as smoking history, education level, baseline history of cardiovascular disease, and gender.
They also performed a sensitivity analysis to examine potential confounding by exposure to secondhand smoke. ::: ::: More than three-quarters of the participants reported currently using incense, and another 13% were former users.
Most had used incense daily for at least 20 years, typically keeping it burning intermittently throughout the day.
The authors estimated that current long-term incense users had a 12% increased risk of cardiovascular mortality compared with former and never users, including a 19% increased risk for stroke and a 10% increased risk for coronary heart disease.1 ::: ::: Previous studies reported concentrations of volatile organic compounds and particulate matter in incense emissions similar to those in cigarette smoke.3,4 Others showed that long-term exposure to incense smoke increased blood vessel inflammation and affected blood flow in rats.5 In vitro studies have indicated adverse impact to human coronary6 and lung cells.4 But this is the first study to provide epidemiological evidence of effects at the population level resulting from habitual day-to-day burning of incense at home, says senior author Woon-Puay Koh, an epidemiologist at Duke–National University of Singapore Graduate Medical School. ::: ::: “This study is of particular significance given that cardiovascular disease is one of the most common chronic diseases in the population worldwide,” says Karin Yeatts, an epidemiologist at the University of North Carolina at Chapel Hill, who has studied indoor air quality in the Middle East.
In contrast with outdoor air pollution, incense exposure may be easier for an individual to avoid, but Yeatts says education will be needed to help people understand the risks of these exposures, similar to educational campaigns about cigarette smoking. ::: ::: Limitations to the study include lack of information on the type of incense burned and the use of ventilation during incense burning.
In addition, participants were asked about their incense exposure only once—during recruitment—and no data were available for nonfatal coronary heart disease or stroke.
A strength of the study is the cohort study design, which provides evidence that the exposure of interest preceded the health outcome. ::: ::: Koh published an earlier prospective study that found an association between incense use and upper respiratory cancer.7 Next she and her coauthors hope to look at cardiovascular risk biomarkers in relation to diseases such as diabetes mellitus and hypertension.
It’s also unclear why the estimated impact on stroke was greater than that on heart disease, says first author An Pan, an epidemiologist at the National University of Singapore.
“That could be very interesting to look at in terms of future research.
” | 18,961 |
Title:
Discord, discordance, and concurrency: comparing individual and partnership-level analyses of new partnerships of young adults at risk of sexually transmitted infections.
Abstract:
BACKGROUND AND OBJECTIVES ::: Partnerships that are discordant by demographic and behavioral characteristics or are concurrent may facilitate transmission of sexually transmitted infections (STIs) by bridging sexual networks. ::: ::: ::: GOAL ::: : The goal of this study was to examine if STI risk within partnerships is associated with discordance and concurrency using the partnership as the unit of analysis.
::: ::: ::: STUDY ::: One hundred ninety-two individuals, in 96 new partnerships, recruited from sexually transmitted disease and family planning clinics, underwent a computer-assisted interview; were tested for chlamydia, gonorrhea, and trichomonas; and their medical records were reviewed.
Partnership variables for discordance by ethnicity, education level, number of lifetime partners, and relationship commitment, as well as concurrency and consistent condom use were tested for associations with partnership STI by chi-squared analysis and logistic regression.
Associations between individual level STI, individual characteristics, relationship commitment, and concurrency were tested in bivariate and multivariate models. ::: ::: ::: RESULTS ::: STI was detected in 22% of partnerships; discordance for demographics or relationship commitment was reported in 40% to 50%; and partner concurrency in 26%.
Few partnerships (18%) reported consistent condom use in the prior month.
In multivariate analyses, partnership-level STI was associated with discordance by ethnicity (odds ratio [OR], 3.4; P = 0.04), commitment (OR, 4.2; P = 0.02), number of lifetime partners (OR, 4.9; P = 0.01), and concurrency (OR, 3.8; P = 0.03).
Individual-level STI was associated with the individual's concurrency and Hispanic ethnicity. ::: ::: ::: CONCLUSIONS ::: Discordance and concurrency are associated with STI at the partnership level and may reflect bridging between high- and low-risk STI networks.
Partnership factors allowed additional assessment of STI risk over individual factors, suggesting that data on partnerships may identify individuals linked to risky networks. | 18,983 |
Title:
Life Satisfaction, Self-Esteem, and Body Image: A Psychosocial Evaluation of Aesthetic and Reconstructive Surgery Candidates
Abstract:
Psychology should be an important part of a plastic surgery procedure in order to buoy up the patient so that he gains a consequent relief of psychiatric and social problems.
It is a fact that reconstructive surgery patients also seek psychological stability and a better appearance that is acceptable to society.
While the life satisfaction, self-esteem, and body image of the individual who seeks aesthetic plastic surgery has been a special concern in the plastic surgery literature, data about reconstructive surgery patients are usually lacking.
To understand the factors influencing the aim of an individual seeking plastic surgery, this prospective controlled clinical study was designed.
We hypothesized that they should have lower life satisfaction and self-esteem and more distorted body images than the ``normal'' population.
Three hundred individuals were included in the study.
Both the aesthetic surgery group (AG) and the reconstructive surgery group (RG) consist of 100 (n= 100) subjects.
Individuals chosen randomly from the total population seen in the 12-month period were included regardless of the type of procedure, body region, or type of trauma as well as whether or not their wish for surgery was justified by the staff.
The third group, the control group (CG), also consists of 100 (n= 100) subjects and was chosen from the ``normal'' population.
All 300 subjects were asked to complete four scales: the Socio-Demographic Questionnaire, Life-Satisfaction Index (LSI), Self-Esteem Inventory (SEI), and Body-Image Inventory (BII).
Results were collected and compared.
The LSI results for the two surgical groups were found to be similar to those for the CG, with the RG demonstrating the lowest level.
For the SEI there was a significant difference between the two surgical groups, being in favor of the AG, and a greater difference was noted between the CG and the RG.
BII results showed no significant difference among the three groups.
As a result, although there may be some, a regular person who seeks an aesthetic procedure should not be considered a psychologically disturbed individual at face value and each case should be evaluated individually in the preoperative consultation.
Similarly, individuals who present for reconstructive procedures and wish further aesthetic refinements should be evaluated and treated exactly as pure aesthetic candidates. | 18,990 |
Title:
The predictive power of the CluSTr database
Abstract:
Summary: The CluSTr database employs a fully automatic single-linkage hierarchical clustering method based on a similarity matrix.
In order to compute the matrix, first all-against-all pair-wise comparisons between protein sequences are computed using the Smith--Waterman algorithm.
The statistical significance of the similarity scores is then assessed using a Monte Carlo analysis, yielding Z-values, which are used to populate the matrix.
This paper describes automated annotation experiments that quantify the predictive power and hence the biological relevance of the CluSTr data.
The experiments utilized the UniProt data-mining framework to derive annotation predictions using combinations of InterPro and CluSTr.
We show that this combination of data sources greatly increases the precision of predictions made by the data-mining framework, compared with the use of InterPro data alone.
We conclude that the CluSTr approach to clustering proteins makes a valuable contribution to traditional protein classifications.
::: ::: Availability: http://www.ebi.ac.uk/clustr/ ::: ::: Contact: [email protected] | 19,082 |
Title:
Evaluating functional localizers: The case of the FFA
Abstract:
Abstract Functional localizers are routinely used in neuroimaging studies to test hypotheses about the function of specific brain areas.
The specific tasks and stimuli used to localize particular regions vary widely from study to study even when the same cortical region is targeted.
Thus, it is important to ask whether task and stimulus changes lead to differences in localization or whether localization procedures are largely immune to differences in tasks and contrasting stimuli.
We present two experiments and a literature review that explore whether face localizer tasks yield differential localization in the fusiform gyrus as a function of task and contrasting stimuli.
We tested standard localization tasks–passive viewing, 1-back, and 2-back memory tests–and did not find differences in localization based on task.
We did, however, find differences in the extent, strength and patterns/reliabilities of the activation in the fusiform gyrus based on comparison stimuli (faces vs. houses compared to faces vs. scrambled stimuli). | 19,085 |
Title:
Seeing I to I: A Pathway to Interpersonal Connectedness
Abstract:
The authors introduce the construct of I-sharing—the belief that one shares an identical subjective experience with another person—and the role it plays in liking.
In Studies 1–3, participants indicated their liking for an objectively similar and an objectively dissimilar person, one of whom I-shared with them and the other of whom did not.
Participants preferred the objectively similar person but only when that person I-shared with them.
Studies 4 and 5 highlight the role that feelings of existential isolation and the need for closeness play in people’s attraction to I-sharers.
In Study 4, people with high needs for interpersonal closeness responded to I-sharers and non-I-sharers with great intensity.
In Study 5, priming participants with feelings of existential isolation increased their liking for I-sharers over objectively similar others.
The results highlight the importance of shared subjective experience and have implications for interpersonal and intergroup processes. | 19,091 |
Title:
The PPAR alpha gene is associated with triglyceride, low-density cholesterol and inflammation marker response to fenofibrate intervention: the GOLDN study
Abstract:
As a peroxisome proliferator-activated receptor alpha (PPARα) agonist, fenofibrate favorably modulates dyslipidemia and inflammation markers, which are associated with cardiovascular risk.
To determine whether variation in the PPARα receptor gene was associated with lipid and inflammatory marker response, we conducted a 3-week trial of fenofibrate in 861 men and women.
Mixed linear models that controlled for age and sex, as well as family pedigree and study center, were constructed using single-nucleotide polymorphisms (SNPs) in the PPARα gene as predictors and changes in fasting triglycerides (TGs), cholesterol and inflammatory markers as outcomes.
Significant associations with low-density cholesterol and interleukin-2 (P<0.001) responses to fenofibrate were found.
Although there were suggestive associations with tumor necrosis factor-alpha and TG responses (P<0.05), these did not survive the correction for multiple testing.
We conclude that variants in the PPARα gene may contribute to future pharmacogenomic paradigms seeking to predict fenofibrate responders from both an anti-dyslipidemic and anti-inflammatory perspective. | 19,135 |
Title:
Central Pontine Myelinolysis in the Hyperosmolar Hyperglycaemic State
Abstract:
Objective: To report a rare association of central pontine myelinolysis (CPM) with hyperosmolar hyperglycaemic state (HHS).
Clinical Presentation and Intervention: A diabetic female presented with HHS and prolonged severe hypernatraemia.
The metabolic derangement was adequately treated with proper correction of both hyperglycaemia and hypernatraemia.
Lack of improvement in the presenting confusional state and the development of a fresh neurological deterioration led to the suspicion of CPM that was confirmed with magnetic resonance imaging.
She fully recovered after 4 weeks with no specific medical treatment.
Conclusion: This case report showed that osmotic demyelination was linked to hypernatraemia and that CPM could result from severe hypernatraemia of HHS. | 19,137 |
Title:
Hypothalamic growth hormone secretagogue receptor regulates growth hormone secretion, feeding, and adiposity
Abstract:
Growth hormone secretagogues (GHSs) stimulate GH secretion and food intake.
GHS receptor (GHS-R) mRNA has been identified mainly in the arcuate nucleus (Arc) and ventromedial nucleus of the hypothalamus and in the pituitary.
Ghrelin, an endogenous ligand for GHS-R, has recently been purified from rat stomach.
Although ghrelin is also expressed in the hypothalamus, the physiological significance of the ghrelin/GHS-R system is still unknown.
We have created transgenic (Tg) rats expressing an antisense GHS-R mRNA under the control of the promoter for tyrosine hydroxylase (TH), thus selectively attenuating GHS-R protein expression in the Arc.
Tg rats had lower body weight and less adipose tissue than did control rats.
Daily food intake was reduced, and the stimulatory effect of GHS treatment on feeding was abolished in Tg rats.
GH secretion and plasma insulin-like growth factor-I levels were reduced in female Tg rats.
These results suggest that GHS-R in the Arc is involved in the regulation of GH secretion, food intake, and adiposity. | 19,197 |
Title:
The human myelin basic protein gene is included within a 179-kilobase transcription unit: expression in the immune and central nervous systems.
Abstract:
Two human Golli (for gene expressed in the oligodendrocyte lineage)-MBP (for myelin basic protein) cDNAs have been isolated from a human oligodendroglioma cell line.
Analysis of these cDNAs has enabled us to determine the entire structure of the human Golli-MBP gene.
The Golli-MBP gene, which encompasses the MBP transcription unit, is approximately 179 kb in length and consists of 10 exons, seven of which constitute the MBP gene.
The human Golli-MBP gene contains two transcription start sites, each of which gives rise to a family of alternatively spliced transcripts.
At least two Golli-MBP transcripts, containing the first three exons of the gene and one or more MBP exons, are produced from the first transcription start site.
The second family of transcripts contains only MBP exons and produces the well-known MBPs.
In humans, RNA blot analysis revealed that Golli-MBP transcripts were expressed in fetal thymus, spleen, and human B-cell and macrophage cell lines, as well as in fetal spinal cord.
These findings clearly link the expression of exons encoding the autoimmunogen/encephalitogen MBP in the central nervous system to cells and tissues of the immune system through normal expression of the Golli-MBP gene.
They also establish that this genetic locus, which includes the MBP gene, is conserved among species, providing further evidence that the MBP transcription unit is an integral part of the Golli transcription unit and suggest that this structural arrangement is important for the genetic function and/or regulation of these genes. | 19,238 |
Title:
Relationship between folding and function in a sequence-specific miniature DNA-binding protein.
Abstract:
Previously, we have described a miniature protein-based approach to the design of molecules that bind DNA or protein surfaces with high affinity and specificity.
In this approach, the small, well-folded protein avian pancreatic polypeptide acts as a scaffold to present and stabilize an alpha-helical or PPII-helical recognition epitope.
The first miniature protein designed in this way, a molecule called p007, presents the alpha-helical recognition epitope found on the bZIP protein GCN4 and binds DNA with nanomolar affinity and exceptional specificity.
In this work we use alanine-scanning mutagenesis to explore the contributions of 29 p007 residues to DNA affinity, specificity, and secondary structure.
Virtually every residue within the p007 alpha-helix, and most residues within the p007 PPII helix, contribute to both DNA affinity and specificity.
These residues include those introduced to make specific and nonspecific DNA contacts, as well as those that complete the miniature protein core.
Moreover, there exists a direct correlation between the affinity of a p007 variant for specific DNA and the ability of that variant to select for specific DNA over nonspecific DNA.
Although we observe no correlation between alpha-helicity and affinity, we observe a limited correlation between alpha-helicity and sequence specificity that emphasizes the role of coupled binding/folding in the function of p007.
Our results imply that formation of a highly evolved set of protein.
DNA contacts in the context of a well-packed hydrophobic core, and not the extent of intrinsic alpha-helical structure, is the primary determinant of p007 function. | 19,306 |
Title:
The role of class 1 and 2 integrons in mediating antimicrobial resistance among canine and feline clinical E. coli isolates from the US
Abstract:
Abstract Integrons are mobile genetic elements that incorporate an open reading frame or gene cassettes.
They have an important role in the acquisition and dissemination of antimicrobial resistance genes.
Yet the occurrence of integrons carrying antimicrobial resistance genes in bacterial pathogens of pet animals is seldom addressed.
The purpose of this study was to describe the incidence of class 1 and 2 integrons in clinical isolates of Escherichia coli ( n = 82) from cats and dogs provided by diagnostic laboratories in five States of the USA.
An association between resistance genes in the integrons and the isolates’ phenotypes was found.
Integrons were detected using PCR and then further characterized by restriction fragment-length polymorphism analysis and amplicon sequencing.
Class 1 integrons were detected in 27% of the isolates, while only 2% ( n = 2) of the isolates were positive for the presence of class 2 integrons.
Seventy-two percent ( n = 59) of the isolates did not carry integrons.
Eleven gene cassettes were found either alone or in combination with other gene cassettes, which encoded resistance to aminoglycosides (aadA1, aadA2, aadA5, aacA4, and aadB), trimethoprim (dfrA1, dhfrA17, and dfrA12), chloramphenicol ( catB3 and cmlA6), and streptothricin (sat1), respectively.
All integron-positive isolates were characterized by resistance to least two drug classes and 35% produced extended-spectrum β-lactamases.
The association of integrons carried on plasmids and antimicrobial resistance was confirmed by curing experiments for three isolates.
Resistance was resolved once large plasmids (size range 97–169 kb) carrying the class 1 integron were lost.
Therefore, integrons appear to have an essential role in facilitating the dissemination of the resistance genes and contributing to the creation of multi-drug resistant phenotypes. | 19,449 |
Title:
Treatment of active lupus nephritis with the novel immunosuppressant 15-deoxyspergualin: an open-label dose escalation study
Abstract:
As the immunosuppressive potency of 15-deoxyspergualin (DSG) has been shown in the therapy of renal transplant rejection and Wegener's granulomatosis, the intention of this study was to evaluate the safety of DSG in the therapy of lupus nephritis (LN).
Patients with histologically proven active LN after prior treatment with at least one immunosuppressant were treated with 0.5 mg/kg normal body weight/day DSG, injected subcutaneously for 14 days, followed by a break of one week.
These cycles were repeated to a maximum of nine times.
Doses of oral corticosteroids were gradually reduced to 7.5 mg/day or lower by cycle 4.
Response was measured according to a predefined decision pattern.
The dose of DSG was adjusted depending on the efficacy and side effects.
A total of 21 patients were included in this phase-I/II study.
After the first DSG injection, one patient was excluded from the study due to renal failure.
Five patients dropped out due to adverse events or serious adverse events including fever, leukopenia, oral candidiasis, herpes zoster or pneumonia.
Eleven out of 20 patients achieved partial (4) or complete responses (7), 8 were judged as treatment failures and 1 patient was not assessable.
Twelve patients completed all nine cycles; in those patients, proteinuria decreased from 5.88 g/day to 3.37 g/day (P = 0.028), Selena-SLEDAI (Safety of Estrogens in Lupus Erythematosus - National Assessment - systemic lupus erythematosus disease activity index) decreased from 17.6 to 11.7.
In 13 out of 20 patients, proteinuria decreased by at least 50%; in 7 patients to less than 1 g/day.
Although the number of patients was small, we could demonstrate that DSG provides a tolerably safe treatment for LN.
The improvement in proteinuria encourages larger controlled trials.
ClinicalTrials.gov: NCT00709722 | 19,472 |
Title:
Genetic analysis of thrips resistance in cowpea (Vigna unguiculata [L.] Walp.)
Abstract:
Flower bud thrips, Megalurothrips sjostedti is the most severe field pest of cowpea that causes massive flower abortion which eventually results to substantial yield reduction in Africa.
There is paucity of information on the mode of gene actions controlling inheritance of resistance to flower bud thrips in cowpea in the literature.
The objectives of study were to assess the genetic variability for thrips resistance among the cowpea germplasm, determined the mode of inheritance of genes that conferred resistance and both broad and narrow-sense heritability estimates for the inheritance of thrips resistance in cowpea.
Twelve cowpea lines were used in crosses in the screen house at IITA, Ibadan.
The mating was accomplished using North Carolina design II to generate 48F1 hybrids, which were eventually evaluated with the parents.
Data on number of peduncles, number of pods and number of thrips per flower were recorded and subjected to analysis of variance using random model by SAS 9.2.
Significant variability was observed for most agronomic and thrip-adaptive traits among the cowpea germplasm, parental-lines and F1 genotypes evaluated.
General combining ability (GCA) and specific combining ability (SCA) mean squares were significant (P < 0.01) for number of pods per plant and other traits under the research environment.
The GCA effect accounted for 68.82–80.07% of the total variation among hybrids for all traits except days to flowering; SCA explained less than 50% of the total variation.
Narrow-sense heritability estimates ranged from 7.53 (days to flower) to 63.92% (number of peduncles per plant).
Additive gene action largely controlled the inheritance of yield components and other traits under thrips infestation and these traits were moderately heritable. | 19,526 |
Title:
Facilitation and Restoration of Cognitive Function in Primate Prefrontal Cortex by a Neuroprosthesis that Utilizes Minicolumn-Specific Neural Firing
Abstract:
Objective.
Maintenance of cognitive control is a major concern for many human disease conditions; therefore, a major goal of human neuroprosthetics is to facilitate and/or recover the cognitive function when such circumstances impair appropriate decision making.
Approach.
Minicolumnar activity from the prefrontal cortex (PFC) was recorded from nonhuman primates trained to perform a delayed match to sample (DMS), via custom-designed conformal multielectrode arrays that provided inter-laminar recordings from neurons in the PFC layer 2/3 and layer 5.
Such recordings were analyzed via a previously demonstrated nonlinear multi-input–multi-output (MIMO) neuroprosthesis in rodents, which extracted and characterized multicolumnar firing patterns during DMS performance.
Main results.
The MIMO model verified that the conformal recorded individual PFC minicolumns responded to entrained target selections in patterns critical for successful DMS performance.
This allowed the substitution of task-related layer 5 neuron firing patterns with electrical stimulation in the same recording regions during columnar transmission from layer 2/3 at the time of target selection.
Such stimulation improved normal task performance, but more importantly, recovered performance when applied as a neuroprosthesis following the pharmacological disruption of decision making in the same task.
Significance.
These findings provide the first successful application of neuroprosthesis in the primate brain designed specifically to restore or repair the disrupted cognitive function. | 19,569 |
Title:
Olanzapine May Inhibit Colonic Motility Associated with the 5-HT Receptor and Myosin Light Chain Kinase
Abstract:
Objective ::: To study whether the effects of olanzapine on gastrointestinal motility is related to the serotonin antagonism and myosin light chain kinase. | 19,588 |
Title:
DNA Barcoding for Identification of Sugarcane Borers in China
Abstract:
Sugarcane borers are economically damaging insects with species that vary in distribution patterns both geographically and temporally, and vary based on ecological niche.
Currently, identification of sugarcane borers is mostly based on morphological characters.
However, morphological identification requires taxonomic expertise.
An alternative method to identify sugarcane borers is the use of molecular data.
DNA barcoding based on partial cytochrome c oxidase subunit 1 (COI) sequences has proven to be a useful tool for rapid and accurate species determination in many insect taxa.
This study was conducted to test the effectiveness of DNA barcodes to discriminate among sugarcane borer species in China.
Partial sequences of the COI gene (709 bp) were obtained from six species collected from different geographic areas.
Results showed that the pairwise intraspecies genetic distance was < 0.02, whereas the interspecies genetic distance ranged from 0.117 to 0.182.
Results from a neighbor-joining tree showed that the six sugarcane borer species were certainly separated.
These results suggested that the partial COI sequences had high barcoding resolution in discriminating among sugarcane borer species.
Our study emphasized the use of DNA barcodes for identification of the analyzed sugarcane borer species and represents an important step for building a comprehensive barcode library for sugarcane borers in China. | 19,659 |
Title:
5-Methyltetrahydrofolate Transport by Hepatoma Cells and Methotrexate-resistant Sublines in Culture
Abstract:
Abstract The properties of the folate transport system in H35 hepatoma cells have been studied by measurirg the transport of (+)-5-methyltetrahydrofolate.
Using initial rates of uptake, it has been demonstrated that the uptake is saturable, carrier mediated, and shared by methotrexate.
The accumulation of (+)-5-methyltetrahydrofolate is concentrative, demonstrating the presence of an active transport process.
A previous study suggested that methotrexate-resistant sublines (H35R) acquired methotrexate insensitivity because of an impaired capacity for transport.
This postulate was substantiated in the present investigation by several observations.
The initial uptake and steady-state level of (+)-5-methyltetrahydrofolate were markedly reduced in the resistant sublines as was the case with methotrexate.
Triazinate (2-{chloro-4-[4,6-diamino-2,2-dimethyl-S-triazine-1(2H)-ylphenoxyl]}-N,N-dimethyl-m-toluamide · ethanesulfonic acid) an inhibitor of dihydrofolate reductase which enters the cells by a pathway independent of the folate coenzyme, was equally toxic to H35 cells and to an H35 subline resistant to 0.3 µM methotrexate.
Resistant sublines that are insensitive to methotrexate up to 1 µm display a transport defect but have normal levels of dihydrofolate reductase.
Sublines resistant to higher levels of methotrexate showed not only defective transport but also commensurate increases in dihydrofolate reductase.
Attempts to demonstrate carrier-dependent transport of (+)-5-methyltetrahydrofolate or methotrexate in resistant sublines were negative, suggesting the lack of a functional carrier.
These properties were readily demonstrated in H35 cells and included temperature dependence, competition for uptake with analogs, and transstimulation. | 19,692 |
Title:
Countercurrent exchange in the renal medulla
Abstract:
The microcirculation of the renal medulla traps NaCl and urea deposited to the interstitium by the loops of Henle and collecting ducts.
Theories have predicted that countercurrent exchanger efficiency is favored by high permeability to solute.
In contrast to the conceptualization of vasa recta as simple "U-tube" diffusive exchangers, many findings have revealed surprising complexity.
Tubular-vascular relationships in the outer and inner medulla differ markedly.
The wall structure and transport properties of descending vasa recta (DVR) and ascending vasa recta (AVR) are very different.
The recent discoveries of aquaporin-1 (AQP1) water channels and the facilitated urea carrier UTB in DVR endothelia show that transcellular as well as paracellular pathways are involved in equilibration of DVR plasma with the interstitium.
Efflux of water across AQP1 excludes NaCl and urea, leading to the conclusion that both water abstraction and diffusion contribute to transmural equilibration.
Recent theory predicts that loss of water from DVR to the interstitium favors optimization of urinary concentration by shunting water to AVR, secondarily lowering blood flow to the inner medulla.
Finally, DVR are vasoactive, arteriolar microvessels that are anatomically positioned to regulate total and regional blood flow to the outer and inner medulla.
In this review, we provide historical perspective, describe the current state of knowledge, and suggest areas that are in need of further exploration. | 19,800 |
Title:
University of Turku in the BioNLP'11 Shared Task
Abstract:
We present a system for extracting biomedical events (detailed descriptions of biomolecular interactions) from research articles, developed for the BioNLP'11 Shared Task.
Our goal is to develop a system easily adaptable to different event schemes, following the theme of the BioNLP'11 Shared Task: generalization, the extension of event extraction to varied biomedical domains.
Our system extends our BioNLP'09 Shared Task winning Turku Event Extraction System, which uses support vector machines to first detect event-defining words, followed by detection of their relationships.
Our current system successfully predicts events for every domain case introduced in the BioNLP'11 Shared Task, being the only system to participate in all eight tasks and all of their subtasks, with best performance in four tasks.
Following the Shared Task, we improve the system on the Infectious Diseases task from 42.57% to 53.87% F-score, bringing performance into line with the similar GENIA Event Extraction and Epigenetics and Post-translational Modifications tasks.
We evaluate the machine learning performance of the system by calculating learning curves for all tasks, detecting areas where additional annotated data could be used to improve performance.
Finally, we evaluate the use of system output on external articles as additional training data in a form of self-training.
We show that the updated Turku Event Extraction System can easily be adapted to all presently available event extraction targets, with competitive performance in most tasks.
The scope of the performance gains between the 2009 and 2011 BioNLP Shared Tasks indicates event extraction is still a new field requiring more work.
We provide several analyses of event extraction methods and performance, highlighting potential future directions for continued development. | 19,801 |
Title:
β-catenin in plants and animals: common players but different pathways
Abstract:
A key node in number of essential cellular processes in eukaryotes, Armadillo was originally characterized in Drosophila as the component of Wingless/Wnt signal transduction pathway (Nusslein-Volhard and Wieschaus, 1980).
β-catenin is the mammalian homolog of Armadillo playing dual role in structural and transcriptional regulation during embryonic development (Conacci-Sorrell et al., 2002).
Even though initially characterized in animals, members of the Armadillo proteins are also known to exist in non-animals including slime mold (Dictyostelium discoideum) and plants (Wang et al., 1998; Barelle et al., 2006; Veses et al., 2009).
The existence of Armadillo repeat family of proteins across species suggests ancient evolutionary origin and functional conservation of these proteins in multicellular organisms (Coates, 2003).
The intricate role of β-catenin raises several doubts about the mechanism by which it mediates interaction with diverse partner proteins using common interface, and how this interaction influences adhesion and transcription? ::: ::: The ARM family proteins have been identified with multiple functional domains in more than one species.
Genome-wide studies in plants have shown the existence of large number of Armadillo homologs in Physcomitrella patens, Arabidopsis and Oryza sativa (Mudgil et al., 2004; Sharma et al., 2014).
One assumption is that, Armadillo family being evolutionary conserved, perform similar role in all organisms.
However, the existence of multigene Armadillo family with various subfamilies indicate novel species specific functions of these proteins in plants.
Several recent studies have made known the function of numerous ARM proteins in Arabidopsis and rice.
Apart from their analogous role in regulation of gene expression and developmental processes, various proteins were discovered to be predominantly involved in plant stress responses.
::: ::: Thus, an intriguing and important question remains as in what way the similar effector proteins of Wnt pathway function and how similar canonical response is prevented or exist in plants.
Recent progress in studies of ARM proteins in plants has suggested some possible answers to this question.
However, the Wnt signaling mechanism regulated by ARM repeat proteins is still unknown.
Regarding this, many underscoring questions are just beginning to emerge that remains to be answered. | 19,823 |
Title:
Costly Nutritious Diets do not Necessarily Translate into Better Performance of Artificially Reared Fruit Flies (Diptera: Tephritidae)
Abstract:
ABSTRACT ::: Protein, lipid, carbohydrate, and energy contents of three artificial diets (Xal2, Met1, and Met2) used for laboratory-rearing and mass-rearing the Mexican fruit fly, Anastrepha ludens (Loew), for a sterile insect technique program were measured.
The larval survival, pupation, pupal weight, adult emergence, sex ratio, and flight capacity of the flies reared on each of these diets were also quantified.
The diet with the highest nutrient and energy content was Xal2 followed by Met2 and Met1, but larval recovery and percent pupation was significantly higher in flies reared on either the Metl or Met2 diets.
A. ludens reared on Xal2 exhibited the highest proportion of adults capable of flight.
No other response variable differed significantly among the three diets tested.
This suggests that a high content of nutrients and multiple sources of protein (dried yeast and wheat germ in the case of the Xal2 diet) do not necessarily improve overall performance or fly quality.
We conclude that nutritious diets for A. ludens can be modified to reduce their cost without compromising the performance of artificially reared flies. | 19,839 |
Title:
Ixodes scapularis (Acari: Ixodidae) Deer Tick Mesoscale Populations in Natural Areas: Effects of Deer, Area, and Location
Abstract:
Nymphal Ixodes scapularis Say deer ticks were collected at 22 parks or other natural areas on Long Island, New York, to examine the relationship between tick populations and geographic position, size of area, presence of white-tailed deer, Odocoileus virginianus (Zimmerman), and numbers of human Lyme disease cases in adjacent communities.
Nymphal ticks were 93% less abundant when deer were absent and were also less common in smaller natural areas.
Geographic position on Long Island was not important.
Tick numbers were significantly correlated with human Lyme disease incidence in adjacent townships.
A second survey of larval ticks from five areas where deer were absent and six where deer were present found larvae present at four of the five sites without deer, but at only 2% of the levels found where deer were present.
These results suggest that populations of I. scapularis can occur and reproduce in the absence of white-tailed deer, so that eradication of all deer would greatly reduce, but not eliminate, all risk of Lyme disease. | 19,916 |
Title:
Long-term and stable correction of uremic anemia by intramuscular injection of plasmids containing hypoxia-regulated system of erythropoietin expression
Abstract:
Relative deficiency in production of glycoprotein hormone erythropoietin (Epo) is a major cause of renal anemia.
This study planned to investigate whether the hypoxia-regulated system of Epo expression, constructed by fusing Epo gene to the chimeric phosphoglycerate kinase (PGK) hypoxia response elements (HRE) in combination with cytomegalovirus immediate-early (CMV IE) basal gene promoter and delivered by plasmid intramuscular injection, might provide a long-term physiologically regulated Epo secretion expression to correct the anemia in adenine-induced uremic rats.
Plasmid vectors (pHRE-Epo) were synthesized by fusing human Epo cDNA to the HRE/CMV promoter.
Hypoxia-inducible activity of this promoter was evaluated first in vitro and then in vivo in healthy and uremic rats (n = 30 per group).
The vectors (pCMV-Epo) in which Epo expression was directed by a constitutive CMV gene promoter served as control.
ANOVA and Student's t-test were used to analyze between-group differences.
A high-level expression of Epo was induced by hypoxia in vitro and in vivo.
Though both pHRE-Epo and pCMV-Epo corrected anemia, the hematocrit of the pCMV-Epo-treated rats exceeded the normal (P < 0.05), but that of the pHRE-Epo-treated rats didn't.
Hypoxia-regulated system of Epo gene expression constructed by fusing Epo to the HRE/CMV promoter and delivered by plasmid intramuscular injection may provide a long-term and stable Epo expression and secretion in vivo to correct the anemia in adenine-induced uremic rats. | 19,921 |
Title:
Persistent Disparity in Prevalence of Current Cigarette Smoking Between US Adolescents With vs. Without a Past-Year Major Depressive Episode
Abstract:
Using data from annual (2004-2010) cross-sectional surveys of nationally representative samples, the prevalence rate of current (i.e., past 30 days) cigarette smoking among US adolescents age 12-17 years was twice as high for those with vs. without a past-year major depressive episode (PYMDE) (22 vs. 11% in the 2004 survey and 16 vs. 8% in the 2010 survey).
The proportion of all US adolescent current smokers who had a PYMDE was about 24% for females; 70-80% of all smokers with PYMDE were females.
The persistently higher smoking rates in US adolescents with vs. without PYMDE emphasizes the need for interventions. | 19,962 |
Title:
The Local Effect of Paf on Leukocyte Adherence to Small Bowel Mesenteric Venules Following Intra-abdominal Contamination
Abstract:
We have previously demonstrated that intra-abdominal contamination increases neutrophil infiltration into the gastrointestinal tract.
The purpose of our current study was twofold: 1) to determine if leukocyte adherence to the mesenteric microvasculature occurred by local peritoneal contamination or by systemic mechanisms; and 2) to assess the role of platelet activation factor (PAF) in this process.
Rats underwent cecal ligation and puncture (CLP), and 4 h after the procedure we used intravital microscopy to visualize the mesenteric microcirculation.
Cecal ligation and puncture increased leukocyte adherence (22.3 ± 5.5 leukocytes/100 μm) vs. sham (2.3 ± 0.9, P < 0.05).
WEB-2086, a PAF receptor antagonist, prevented this increase (6.47 ± 4.8, P < 0.05).
To assess if leukocyte adherence was due to topical effects, we performed similar experiments with the small bowel exteriorized.
In such cases, CLP did not increase leukocyte adherence (1.2 ± 0.8 vs. 1.4 ± 0.9).
In addition, topical application of highly diluted fecal matter (1 : 1000) increased leukocyte adherence (4.8 ± 1.2) vs. control (0.6 ± 0.3, P < 0.05).
Our study demonstrates that leukocyte adherence in the mesenteric microcirculation following intra-abdominal contamination is due to direct topical exposure to fecal matter, and it is mediated by PAF. | 20,033 |
Title:
Prognostic indices for brain metastases – usefulness and challenges
Abstract:
BackgroundThis review addresses the strengths and weaknesses of 6 different prognostic indices, published since the Radiation Therapy Oncology Group (RTOG) developed and validated the widely used 3-tiered prognostic index known as recursive partitioning analysis (RPA) classes, i.e. between 1997 and 2008.
In addition, other analyses of prognostic factors in groups of patients, which typically are underrepresented in large trials or databases, published in the same time period are reviewed.
MethodsBased on a systematic literature search, studies with more than 20 patients were included.
The methods and results of prognostic factor analyses were extracted and compared.
The authors discuss why current data suggest a need for a more refined index than RPA.ResultsSo far, none of the indices has been derived from analyses of all potential prognostic factors.
The 3 most recently published indices, including the RTOG's graded prognostic assessment (GPA), all expanded from the primary 3-tiered RPA system to a 4-tiered system.
The authors' own data confirm the results of the RTOG GPA analysis and support further evaluation of this tool.
ConclusionThis review provides a basis for further refinement of the current prognostic indices by identifying open questions regarding, e.g., performance of the ideal index, evaluation of new candidate parameters, and separate analyses for different cancer types.
Unusual primary tumors and their potential differences in biology or unique treatment approaches are not well represented in large pooled analyses. | 20,039 |
Title:
Successful SCT for Nijmegen breakage syndrome
Abstract:
Nijmegen breakage syndrome (NBS) is characterized by chromosomal instability, radiation hypersensitivity, characteristic facial appearance, immunodeficiency and strong predisposition to lymphoid malignancy.
Traditionally, NBS patients have not undergone hematopoietic SCT (HSCT) owing to concerns about increased toxicity.
We therefore report on the HSCT experience in NBS patients in Europe.
Six patients were transplanted either for resistant or secondary malignancy (four patients) or severe immunodeficiency (two patients).
Five patients received reduced-intensity conditioning regimens.
After a median follow-up of 2.2 years, five patients are alive and well.
One patient who received myeloablative conditioning died from sepsis before engraftment.
Acute GVHD grades I–II occurred in three of five patients, mild chronic GVHD in one.
All five surviving patients exhibit restored T-cell immunity.
The experience in these six patients suggests that HSCT in NBS is feasible, can correct the immunodeficiency and effectively treat malignancy.
Acute toxicity seems to be reasonable with reduced-intensity conditioning regimens. | 20,078 |
Title:
Neuronal programmed cell death induces glial cell division in the adult Drosophila brain
Abstract:
Although mechanisms that lead to programmed cell death (PCD) in neurons have been analysed extensively, little is known about how surrounding cells coordinate with it.
Here we show that neuronal PCD in the Drosophila brain induces glial cell division.
We identified PCD in neurons and cell division in glia occurring in a consistent spatiotemporal manner in adult flies shortly after eclosion.
Glial division was suppressed when neuronal PCD was inhibited by ectopic expression of the caspase inhibitor gene p35, indicating their causal relationship.
Glia also responded to neural injury in a similar manner: both stab injury and degeneration of sensory axons in the brain caused by antennal ablation induced glial division.
Eiger, a tumour necrosis factor superfamily ligand, appears to be a link between developmental PCD/neural injury and glial division, as glial division was attenuated in eiger mutant flies.
Whereas PCD soon after eclosion occurred in eiger mutants as in the wild type, we observed excess neuronal PCD 2 days later, suggesting a protective function for Eiger or the resulting glial division against the endogenous PCD.
In older flies, between 6 and 50 days after adult eclosion, glial division was scarcely observed in the intact brain.
Moreover, 8 days after adult eclosion, glial cells no longer responded to brain injury.
These results suggest that the life of an adult fly can be divided into two phases: the first week, as a critical period for neuronal cell death-associated glial division, and the remainder. | 20,096 |
Title:
Variance estimation in the analysis of microarray data
Abstract:
Microarrays are one of the most widely used high throughput technologies.
One of the main problems in the area is that conventional estimates of the variances that are required in the t-statistic and other statistics are unreliable owing to the small number of replications.
Various methods have been proposed in the literature to overcome this lack of degrees of freedom problem.
In this context, it is commonly observed that the variance increases proportionally with the intensity level, which has led many researchers to assume that the variance is a function of the mean.
Here we concentrate on estimation of the variance as a function of an unknown mean in two models: the constant coefficient of variation model and the quadratic variance-mean model.
Because the means are unknown and estimated with few degrees of freedom, naive methods that use the sample mean in place of the true mean are generally biased because of the errors-in-variables phenomenon.
We propose three methods for overcoming this bias.
The first two are variations on the theme of the so-called heteroscedastic simulation-extrapolation estimator, modified to estimate the variance function consistently.
The third class of estimators is entirely different, being based on semiparametric information calculations.
Simulations show the power of our methods and their lack of bias compared with the naive method that ignores the measurement error.
The methodology is illustrated by using microarray data from leukaemia patients. | 20,118 |
Title:
Fractional anisotropy distributions in 2‐ to 6‐year‐old children with autism
Abstract:
Background Increasing evidence suggests that autism is a disorder of distributed neural networks that may exhibit abnormal developmental trajecto- ries.
Characterisation of white matter early in the developmental course of the disorder is critical to understanding these aberrant trajectories.
Methods A cross-sectional study of 2 -t o6-year-old children with autism was conducted using diffusion tensor imaging combined with a novel statistical approach employing fractional anisotropy distribu- tions.
Fifty-eight children aged 18-79 months were imaged: 33 were diagnosed with autism, 8 with general developmental delay, and 17 were typically developing.
Fractional anisotropy values within global white matter, cortical lobes and the cerebel- lum were measured and transformed to random F distributions for each subject.
Each distribution of values for a region was summarised by estimating d, | 20,145 |
Title:
Immunomodulation of allergic responses by targeting costimulatory molecules
Abstract:
PURPOSE OF REVIEW: This review focuses on putative targets, including costimulatory and additional pathways involving T regulatory cells, that may be critical for modifying allergic responses.
RECENT FINDINGS: Multiple costimulatory signals including CD28/CTLA4: CD80/CD86, ICOS: ICOSL, OX40:OX40L and PD-1: PD-L1/PD-L2 have been identified and implicated in the regulation of immune disorders.
Recent studies indicate that T regulatory cells may also suppress T cell costimulation by the secretion of TGF-beta and IL-10, suggesting an important role of T regulatory cells in the regulation of allergic disorders.
SUMMARY: Immune-mediated disorders, including allergic diseases, have been increasing in prevalence.
Unravelling these immune pathways may suggest new targets for immunomodulation. | 20,147 |
Title:
Differentially Expressed Genes in Resistant and Susceptible Common Bean (Phaseolus vulgaris L.) Genotypes in Response to Fusarium oxysporum f. sp. phaseoli
Abstract:
Fusarium wilt of common bean (Phaseolus vulgaris L.), caused by Fusarium oxysporum Schlechtend.:Fr.
f.sp.
phaseoli (Fop), is one of the most important diseases of common beans worldwide.
Few natural sources of resistance to Fop exist and provide only moderate or partial levels of protection.
Despite the economic importance of the disease across multiple crops, only a few of Fop induced genes have been analyzed in legumes.
Therefore, our goal was to identify transcriptionally regulated genes during an incompatible interaction between common bean and the Fop pathogen using the cDNA amplified fragment length polymorphism (cDNA-AFLP) technique.
We generated a total of 8,730 transcript-derived fragments (TDFs) with 768 primer pairs based on the comparison of a moderately resistant and a susceptible genotype.
In total, 423 TDFs (4.9%) displayed altered expression patterns after inoculation with Fop inoculum.
We obtained full amplicon sequences for 122 selected TDFs, of which 98 were identified as annotated known genes in different functional categories based on their putative functions, 10 were predicted but non-annotated genes and 14 were not homologous to any known genes.
The 98 TDFs encoding genes of known putative function were classified as related to metabolism (22), signal transduction (21), protein synthesis and processing (20), development and cytoskeletal organization (12), transport of proteins (7), gene expression and RNA metabolism (4), redox reactions (4), defense and stress responses (3), energy metabolism (3), and hormone responses (2).
Based on the analyses of homology, 19 TDFs from different functional categories were chosen for expression analysis using quantitative RT-PCR.
The genes found to be important here were implicated at various steps of pathogen infection and will allow a better understanding of the mechanisms of defense and resistance to Fop and similar pathogens.
The differential response genes discovered here could also be used as molecular markers in association mapping or QTL analysis. | 20,201 |
Title:
Protein transfer of glycosyl-phosphatidylinositol-B7-1 into tumor cell membranes: a novel approach to tumor immunotherapy.
Abstract:
Modification of tumor cells with one or more costimulatory adhesion molecules has been proposed as a means to develop therapeutic cancer vaccines for use in human immunotherapy.
Expression of B7-1 (CD80) in tumors by gene transfer creates an immunogenic tumor cell that induces antitumor immunity and protects mice from further challenge with wild-type tumor cells.
In this report, we demonstrate that protein transfer of glycosyl-phosphatidylinositol (GPI)-anchored costimulatory molecules into tumor cell membranes could be used as an alternative to gene transfer for tumor immunotherapy.
Incubation of isolated tumor membranes with purified GPI-anchored B7-1 results in stable incorporation of B7-1 on tumor cell membranes within a few hours.
Immunization of C57BL/6 mice with EG7 tumor membranes modified to express GPI-B7-1 by protein transfer induces tumor-specific T-cell proliferation and CTLs.
In addition, immunization with these EG7 membranes protects mice from parental tumor challenge.
The protein transfer approach used here does not require foreign vectors or live tumor cells and is completed within a matter of hours.
Irradiated cells or membrane preparations from fresh or frozen tumor tissue can be used.
Therefore, protein transfer of glycolipid-anchored molecules provides an efficient and novel approach to modify tumor membranes for human immunotherapy.
This approach is not limited to costimulatory molecules because any cell surface protein can be converted to a GPI-anchored form by recombinant techniques. | 20,343 |
Title:
Determining Relative Contributions of Vegetation and Topography to Burn Severity from LANDSAT Imagery
Abstract:
Fire is a dominant process in boreal forest landscapes and creates a spatial patch mosaic with different burn severities and age classes.
Quantifying effects of vegetation and topography on burn severity provides a scientific basis on which forest fire management plans are developed to reduce catastrophic fires.
However, the relative contribution of vegetation and topography to burn severity is highly debated especially under extreme weather conditions.
In this study, we hypothesized that relationships of vegetation and topography to burn severity vary with fire size.
We examined this hypothesis in a boreal forest landscape of northeastern China by computing the burn severity of 24 fire patches as the difference between the pre- and post-fire Normalized Difference Vegetation Index obtained from two Landsat TM images.
The vegetation and topography to burn severity relationships were evaluated at three fire-size levels of small ( 1,000 ha, n = 3).
Our results showed that vegetation and topography to burn severity relationships were fire-size-dependent.
The burn severity of small fires was primary controlled by vegetation conditions (e.g., understory cover), and the burn severity of large fires was strongly influenced by topographic conditions (e.g., elevation).
For moderate fires, the relationships were complex and indistinguishable.
Our results also indicated that the pattern trends of relative importance for both vegetation and topography factors were not dependent on fire size.
Our study can help managers to design fire management plans according to vegetation characteristics that are found important in controlling burn severity and prioritize management locations based on the relative importance of vegetation and topography. | 20,348 |
Title:
Multiplex PCR for Detection of Aminoglycoside Resistance Genes in Enterococci
Abstract:
A multiplex PCR procedure for detecting the aminoglycoside resistance genes aac(6')-Ie-aph(2")-Ia, aph(2")-Ib, aph(2")-Ic, aph(2")-Id, aph(3')-IIIa, and ant(4')-Ia was evaluated and found to determine accurately the presence of these genes in enterococci. | 20,359 |
Title:
The uncertain role of unmodified mesenchymal stem cells in tumor progression: what master switch?
Abstract:
Mesenchymal stem cells (MSCs) are emerging as promising gene vectors for cancer therapy because of their unique characteristics, including the ease of their expansion and genetic modification and their remarkable tumor-tropic properties.
However, there remains a concern that MSCs may promote cancer progression.
Surprisingly, there are conflicting reports within the literature describing both the promotion and inhibition of cancer progression by MSCs.
The reasons for this discrepancy are still unknown.
The surface markers, differentiation ability, and tumorigenic roles of MSCs, as well as their effect on immunoregulation, produce heterogeneity.
In this review, we describe the heterogeneity of MSCs by the species from which they are derived, the methodology for their isolation and the context of their interactions with cancer cells.
The conflicting roles of MSCs in tumor progression may be attributable to the bimodal effect of unmodified MSCs on immunoregulation.
MSCs have been reported to suppress T-cell function and inhibit graft-versus-host disease (GVHD).
On the other hand, MSCs elicit the graft-versus-tumor (GVT) effect in some cases.
Selective allodepletion may be used to dissociate GVHD from the GVT effect.
Understanding the conditions that balance GVHD and the GVT effect of MSCs may be crucial to advance cancer therapy research with respect to MSCs. | 20,623 |
Title:
-Myosin Heavy Chain: A Sarcomeric Gene Associated With Dilated and Hypertrophic Phenotypes of Cardiomyopathy
Abstract:
Background— Mutations in the β-myosin heavy-chain (βMyHC) gene cause hypertrophic (HCM) and dilated (DCM) forms of cardiomyopathy.
In failing human hearts, downregulation of αMyHC mRNA or protein has been correlated with systolic dysfunction.
We hypothesized that mutations in αMyHC could also lead to pleiotropic cardiac phenotypes, including HCM and DCM.
Methods and Results— A cohort of 434 subjects, 374 (134 affected, 214 unaffected, 26 unknown) belonging to 69 DCM families and 60 (29 affected, 30 unaffected, 1 unknown) in 21 HCM families, was screened for αMyHC gene (MYH6) mutations.
Three heterozygous MYH6 missense mutations were identified in DCM probands (P830L, A1004S, and E1457K; 4.3% of probands).
A Q1065H mutation was detected in 1 of 21 HCM probands and was absent in 2 unaffected offspring.
All MYH6 mutations were distributed in highly conserved residues, were predicted to change the structure or chemical bonds of αMyHC, and were absent in at least 300 control chromosomes from an ethnically simi... | 20,640 |
Title:
A Simple Neural Network Exhibiting Selective Activation of Neuronal Ensembles: From Winner-Take-All to Winners-Share-All
Abstract:
A neuroecological equation of the Lotka-Volterra type for mean firing rate is derived from the conventional membrane dynamics of a neural network with lateral inhibition and self-inhibition.
Neural selection mechanisms employed by the competitive neural network receiving external input sare studied with analytic and numerical calculations.
A remarkable finding is that the strength of lateral inhibition relative to that of self-inhibition is crucial for determining the steady states of the network among three qualitatively different types of behavior.
Equal strength of both types of inhibitory connections leads the network to the well-known winner-take-all behavior.
If, however, the lateral inhibition is weaker than the self-inhibition, a certain number of neurons are activated in the steady states or the number of winners is in general more than one (the winners-share-all behavior).
On the other hand, if the self-inhibition is weaker than the lateral one, only one neuron is activated, but the winner is no... | 20,681 |
Title:
Changes in volunteering among young old in the Netherlands between 1992 and 2002: the impact of religion, age-norms, and intergenerational transmission
Abstract:
The positive trend in volunteering among the Dutch young old may in part be due to a relatively favorable disposition to volunteer.
Using data from the Longitudinal Aging Study Amsterdam, volunteering rates of 55–64 year olds in 1992 and 2002 were compared and associated with (among others) three types of dispositional factors: religious involvement, age-related engagement norms, and parental socialization.
The recent cohort was less religiously involved, but more supportive of social engagement at older age, and more often had parents who volunteered, were religiously involved or higher educated.
Multivariate analyses revealed that cohort differences were largely explained by cohort differences in educational level and religious involvement.
It is concluded that their lower religious level suppresses the volunteering rate of the current young old.
To compensate for the decline in religious young old, family and the broader society will become more important for stimulating volunteer work in the future. | 20,707 |
Title:
Cleft lip with or without cleft palate: associations with transforming growth factor alpha and retinoic acid receptor loci.
Abstract:
Summary The first association study of cleft lip with or without cleft palate (CLIP), with candidate genes, found an association with the transforming growth-factor alpha (TGFA) locus.
This finding has since been replicated, in whole or in part, in three independent studies.
Here we extend our original analysis of the TGFA TaqI RFLP to two other TGF A RFLPs and seven other RFLPs at five candidate genes in 117 nonsyndromic cases of CLIP and 113 controls.
The other candidate genes were the retinoic acid receptor (RARA), the bcl-2 oncogene, and the homeobox genes 2F, 2G, and EN2.
Significant associations with the TGFA TaqI and BamHI RFLPs were confirmed, although associations of clefting with previously reported haplotypes did not reach significance.
Of particular interest, in view of the known teratogenic role of retinoic acid, was a significant association with the RARA Pstl RFLP (P = .016; not corrected for multiple testing).
The effect on risk of the A2 allele appears to be additive, and although the A2A2 homozygote only has an odds ratio of about 2 and recurrence risk to first-degree relatives (AI) of 1.06, because it is so common it may account for as much as a third of the attributable risk of clefting.
There is no evidence of interaction between the TGF A and RARA polymorphisms on risk, and jointly they appear to account for almost half the attributable risk of clefting. | 20,726 |
Title:
Blood Loss in Total Knee Arthroplasty
Abstract:
Patients undergoing total knee arthroplasty (TKA) have expected blood loss during and after surgery.
The morbidity associated with blood loss and the burden of blood transfusions in adult arthroplasty necessitates preoperative optimization as routine practice.
Current literature remains inconclusive on which TKA surgical instrumentation techniques are effective in minimizing perioperative blood loss, and consequently lower transfusion rates.
The primary objective of this retrospective review, of a prospective randomized cohort study, was to compare surgical and patient factors, and their influence on blood loss and transfusions rates, between one type of patient-specific instrumentation (PSI), navigated computer-assisted surgery (CAS), and conventional TKA surgical techniques.
A cohort of 128 matched patients (38 PSI, 44 CAS, 46 conventional surgeries) were compared.
Preoperative factors analyzed included; age, gender, body mass index, preoperative hemoglobin (Hb) (g/L), international normalized ratio, use of anticoagulants and comorbid bleeding diathesis.
Maximal Hb drop and transfusion requirements were compared on day 1 to 3.
Perioperative factors collected included: surgical time, tourniquet time, drain output, in situ drain time, order of tibia or femoral cut, and intraoperative loss from suction.
The three groups did not differ on the preoperative patient demographics examined.
The difference between preoperative Hb and the lowest postoperative Hb readings did not differ between study groups (p = 0.39).There are no statistically significant differences in blood loss when comparing PSI versus CAS versus conventional TKA.
Although emerging evidence on PSI is encouraging, the PSI technique for TKA does not result in reduced blood loss.
The study was registered with ClinicalTrials.gov: NCT01145157. | 20,730 |
Title:
The contribution of activity-dependent synaptic plasticity to classical conditioning in Aplysia.
Abstract:
Plasticity at central synapses has long been thought to be the most likely mechanism for learning and memory, but testing that idea experimentally has proven to be difficult.
For this reason, we have developed a simplified preparation of the Aplysia siphon withdrawal reflex that allows one to examine behavioral learning and memory while simultaneously monitoring synaptic connections between individual identified neurons in the CNS.
We previously found that monosynaptic connections from LE siphon sensory neurons to LFS siphon motor neurons make a substantial contribution to the reflex in the siphon withdrawal preparation (Antonov et al., 1999a).
We have now used that preparation to assess the contribution of various cellular mechanisms to classical conditioning of the reflex with a siphon tap conditioned stimulus (CS) and tail shock unconditioned stimulus (US).
We find that, compared with unpaired training, paired training with the CS and US produces greater enhancement of siphon withdrawal and evoked firing of LFS neurons, greater facilitation of the complex PSP elicited in an LFS neuron by the siphon tap, and greater facilitation of the monosynaptic PSP elicited by stimulation of a single LE neuron.
Moreover, the enhanced facilitation of monosynaptic LE-LFS PSPs is greater for LE neurons that fire during the siphon tap and correlates significantly with the enhancement of siphon withdrawal and evoked firing of the LFS neurons.
These results provide the most direct evidence to date that activity-dependent plasticity at specific central synapses contributes to behavioral conditioning and support the idea that synaptic plasticity is a mechanism of learning and memory more generally. | 20,794 |
Title:
Japanese health care: low cost through regulated fees
Abstract:
Prologue: Japans health care system represents an enigma for Americans.
The system incorporates features that Americans value highly: employment-based health insurance, free consumer choice of physician, and a delivery system that leaves clinical decision making in the hands of the doctor.
But the cost of medical care in Japan is very low, compared with that in the United States, thus raising the question: How does Japan provide ready access to care for all of its citizens at a cost that is the lowest among major industrialized nations?
In this essay, Naoki Ikegami describes the basic structure of the Japanese system, how it constrains expenditures, and the major issues it faces.
Ikegami is a rare figure in the Japanese system because his interests span clinical medicine and health policy—a combination that is far more commonly found in the United States.
Ikegami, who trained as a psychiatrist and started his research activities on the epidemiology of alcoholism, is a professor of health and public servic... | 20,882 |
Title:
Predictive validity of the Biomedical Admissions Test: an evaluation and case study.
Abstract:
There has been an increase in the use of pre-admission selection tests for medicine.
Such tests need to show good psychometric properties.
Here, we use a paper by Emery and Bell [2009.
The predictive validity of the Biomedical Admissions Test for preclinical examination performance.
Med Educ 43:557–564] as a case study to evaluate and comment on the reporting of psychometric data in the field of medical student selection (and the comments apply to many papers in the field).
We highlight pitfalls when reliability data are not presented, how simple zero-order associations can lead to inaccurate conclusions about the predictive validity of a test, and how biases need to be explored and reported.
We show with BMAT that it is the knowledge part of the test which does all the predictive work.
We show that without evidence of incremental validity it is difficult to assess the value of any selection tests for medicine. | 20,887 |
Title:
Genomic Evolution of the Proteasome System Among Hemiascomycetous Yeasts
Abstract:
Components of the proteasome-ubiquitin pathway are highly conserved throughout eukaryotic organisms.
In S. cerevisiae, the expression of proteasomal genes is subject to concerted control by a transcriptional regulator, Rpn4p, interacting with a highly conserved cis-regulatory element, PACE, located in the upstream regions of these genes.
Taking advantage of sequence data accumulated from 15 Hemiascomycetes, we performed an in silico study to address the problem of how this system might have evolved among these species.
We found that in all these species the Rpn4p homologues are well conserved in terms of sequence and characteristic domain features.
The "PACE patterns" turned out to be nearly identical among the Saccharomyces "sensu stricto" species, whereas in the evolutionary more distant species the putatively functional cis-regulatory motifs revealed deviations from the "canonical" PACE nonamere sequence in one or two nucleotides.
Our findings suggest that during evolution of the Hemiascomycetes such slightly divergent ancestral motifs have converged into a unique PACE element for the majority of the proteasomal genes within the most recent species of this class.
Likewise, the Rpn4 factors within the most recent species of this class show a higher degree of similarity in sequence than their ancestral counterparts.
By contrast, we did not detect PACE-like motifs among the proteasomal genes in other eukaryotes, such as S. pombe, several filamentous fungi, A. thaliana, or humans, leaving the interesting question which type of concerted regulation of the proteasome system has developed in species other than the Hemiascomycetes. | 20,892 |
Title:
Subcutaneous immunoglobulin therapy: a new option for patients with primary immunodeficiency diseases
Abstract:
Since the 1950s, replacement of immunoglobulin G using human immunoglobulin has been the standard treatment for primary immunodeficiency diseases with defects in antibody production.
These patients suffer from recurrent and severe infections, which cause lung damage and shorten their life span.
Immunoglobulins given intravenously (IVIG) every 3–4 weeks are effective in preventing serious bacterial infections and improving the quality of life for treated patients.
Administration of immunoglobulin subcutaneously (SCIG) is equally effective in preventing infections and has a lower incidence of serious adverse effects compared to IVIG.
The tolerability and acceptability of SCIG has been demonstrated in numerous studies showing improvements in quality of life and a preference for subcutaneous immunoglobulin therapy in patients with antibody deficiencies. | 20,957 |
Title:
Hepatocellular carcinoma: current trends in worldwide epidemiology, risk factors, diagnosis, and therapeutics
Abstract:
Hepatocellular carcinoma (HCC) is a common malignancy in developing countries and its incidence is on the rise in the developing world.
The epidemiology of this cancer is unique since its risk factors, including hepatitis C and B, have been clearly established.
The current trends in the shifting incidence of HCC in different regions of the world can be explained partly by the changing prevalence of hepatitis.
Early detection offers the only hope for curative treatment for patients with HCC, hence effective screening strategies for high-risk patients is of utmost importance.
Liver transplantation and surgical resection remains the cornerstone of curative treatment.
But major advances in locoregional therapies and molecular-targeted therapies for the treatment of advanced HCC have occurred recently.
In this review, current trends in the worldwide epidemiology, surveillance, diagnosis, standard treatments, and the emerging therapies for HCC are discussed. | 21,036 |
Title:
Evaluation of limit feeding corn and distillers dried grains with solubles in non-feed-withdrawal molt programs for laying hens
Abstract:
An experiment was conducted using 504 Hy-Line W-36 Single Comb White Leghorn hens (69 wk of age) randomly assigned to 1 of 7 treatments.
These treatments consisted of a 47% corn:47% soy hulls diet (C:SH) fed ad libitum; a 94% corn diet fed at a rate of 36.3, 45.4, or 54.5 g/hen per day (CORN 36, CORN 45, and CORN 54, respectively): and a 94% corn distillers dried grains with solubles (DDGS) diet fed at the same rates as the previous corn diets (DDGS 36, DDGS 45, and DDGS 54, respectively) during the molt period of 28 d. The intent was to feed the DDGS diets for 28 d; however, all hens on these diets had very low feed intakes and greater than anticipated BW loss.
Thus, they were switched to a 16% CP corn-soybean meal layer diet on d 19 of the molt period.
At d 28, hens on all treatments were fed the same corn-soybean meal layer diet for 39 wk (73 to 112 wk of age).
All DDGS diets and the CORN 36 diet resulted in total cessation of egg production during the molt period and egg production of hens fed the CORN 45, CORN 54, and C:SH diets had decreased to 3 and 4%, respectively, by d 28.
Body weight loss during the 28-d molt period ranged from 14% for the CORN 54 diet to approximately 23% for the 3 DDGS diets.
Postmolt egg production (5 to 43 wk) was higher for hens fed the DDGS molt diets than those fed the corn diets.
There were no consistent differences in egg mass, egg-specific gravity, feed efficiency, or layer feed consumption among molt treatments for the postmolt period.
These results indicate that limit feeding corn diet and DDGS diet in non-feed-withdrawal molt programs will yield long-term postmolt performance that is comparable to that observed by ad libitum feeding a C:SH diet. | 21,109 |
Title:
Chlorogenic Acid Decreases Retinal Vascular Hyperpermeability in Diabetic Rat Model
Abstract:
To evaluate the effect of chlorogenic acid (CGA), a polyphenol abundant in coffee, on retinal vascular leakage in the rat model of diabetic retinopathy, Sprague-Dawley rats were divided into four groups: controls, streptozotocin-induced diabetic rats, and diabetic rats treated with 10 and 20 mg/kg chlorogenic acid intraperitoneally daily for 14 days, respectively.
Blood-retinal barrier (BRB) breakdown was evaluated using FITC-dextran.
Vascular endothelial growth factor (VEGF) distribution and expression level was evaluated with immunohistochemistry and Western blot analysis.
Expression of tight junction proteins, occludin and claudin-5, and zonula occludens protein, ZO-1 was also evaluated with immunohistochemistry and Western blot analysis.
BRB breakdown and increased vascular leakage was found in diabetic rats, with increased VEGF expression and down-regulation of occludin, claudin-5, and ZO-1.
CGA treatment effectively preserved the expression of occludin, and decreased VEGF levels, leading to less BRB breakdown and less vascular leakage.
CGA may have a preventive role in BRB breakdown in diabetic retinopathy by preserving tight junction protein levels and low VEGF levels. | 21,117 |
Title:
Hippocampal cell death following ischemia: Effects of brain temperature and anesthesia
Abstract:
Abstract The effect of brain temperature and anesthesia on ischemic neuronal damage was studied in the hippocampal formation using the four vessel occulusion model in awake and anesthetized rats.
Neuronal damage was assessed by immunocytochemistry and silver impregnation of tissue sections.
The degree of ischemia was monitored by recording spontaneous and evoked electrical activity from the hippocampus and dentate gyrus in all animals.
In addition, the hippocampal temperature and oxygen tension were also recorded using a chamber-type thin-film microelectrode in the anesthetized animals.
Fifteen minutes ischemia in the awake animals caused greater neuronal damage and mortality of animals than 30 min ischemia in anesthetized rats.
The temperature of the brain was found to drop by 4–6°C during complete forebrain ischemia in the latter group.
Neuronal damage was observed infrequently in the hippocampus of these animals.
When the brain temperature was kept constant at the preischemic level during 30 min occlusion, all animals died within a day, while after 15 min occlusion the majority showed an almost complete degeneration of CA1 pyramidal cells and hilar somatostatin immunoreactive neurons.
Following 15 min ischemia, the awake animals showed a similar cell loss in the CA1 region and the hilus.
It is concluded that, in the anesthetized animals prepared for acute recording, the decreased temperature of the brain during ischemia is a major factor in protecting neurons from damage, but that Equithesin anesthesia also has a significant protective effect.
Consistent ischemic degeneration occurs in awake animals by four vessel occlusion, if the brain temperature is controlled and the completeness of ischemia is monitored by recording spontaneous and evoked electrical activity with chronic electrodes. | 21,126 |
Title:
Discovery and Replication of Gene Influences on Brain Structure Using LASSO Regression
Abstract:
We implemented LASSO (least absolute shrinkage and selection operator) regression to evaluate gene effects in genome-wide association studies (GWAS) of brain images, using an MRI-derived temporal lobe volume measure from 729 subjects scanned as part of the Alzheimer’s Disease Neuroimaging Initiative (ADNI).
Sparse groups of SNPs in individual genes were selected by LASSO, which identifies efficient sets of variants influencing the data.
These SNPs were considered jointly when assessing their association with neuroimaging measures.
We discovered 22 genes that passed genome-wide significance for influencing temporal lobe volume.
This was a substantially greater number of significant genes compared to those found with standard, univariate GWAS.
These top genes are all expressed in the brain and include genes previously related to brain function or neuropsychiatric disorders such as MACROD2, SORCS2, GRIN2B, MAGI2, NPAS3, CLSTN2, GABRG3, NRXN3, PRKAG2, GAS7, RBFOX1, ADARB2, CHD4 and CDH13.
The top genes we identified with this method also displayed significant and widespread post-hoc effects on voxelwise, tensor-based morphometry (TBM) maps of the temporal lobes.
The most significantly associated gene was an autism susceptibility gene known as MACROD2.
We were able to successfully replicate the effect of the MACROD2 gene in an independent cohort of 564 young, Australian healthy adult twins and siblings scanned with MRI (mean age: 23.8±2.2 SD years).
In exploratory analyses, three selected SNPs in the MACROD2 gene were also significantly associated with performance intelligence quotient (PIQ).
Our approach powerfully complements univariate techniques in detecting influences of genes on the living brain. | 21,146 |
Title:
Evaluation of neuropsychological function in patients with liver cirrhosis with special reference to their driving ability
Abstract:
Ability to drive an automobile was evaluated in 16 patients with well compensated liver cirrhosis.
Four tests were performed, namely the emergency reaction test, the continuous emergency reaction test, the signal confirmation test and the accelerator reaction test.
Test scores were compared to those of a group of age-matched healthy volunteers.
31% of patients were found to be unfit to drive.
Alcoholic cirrhotics fared as poorly as non-alcoholic cirrhotics.
In patients with subclinical hepatic encephalopathy (defined by neuropsychologic testing), 44% were unfit to drive.
Routine testing of cirrhotic patients for ability to drive could have a major impact on motor vehicle accident rates. | 21,228 |
Title:
Genome-wide Allelic State Analysis on Flow-Sorted Tumor Fractions Provides an Accurate Measure of Chromosomal Aberrations
Abstract:
Chromosomal aberrations are a common characteristic of cancer and are associated with copy number abnormalities and loss of heterozygosity (LOH).
Tumor heterogeneity, low tumor cell percentage, and lack of knowledge of the DNA content impair the identification of these alterations especially in aneuploid tumors.
To accurately detect allelic changes in carcinomas, we combined flow-sorting and single nucleotide polymorphism arrays.
Cells derived from archival cervical and colon cancers were flow-sorted based on differential vimentin and keratin expression and DNA content and analyzed on single nucleotide polymorphism arrays.
A new algorithm, the lesser allele intensity ratio, was used to generate a molecular measure of chromosomal aberrations for each case.
Flow-sorting significantly improved the detection of copy number abnormalities; 31.8% showed an increase in amplitude and 23.2% were missed in the unsorted fraction, whereas 15.9% were detected but interpreted differently.
Integration of the DNA index in the analysis enabled the identification of the allelic state of chromosomal aberrations, such as LOH ([A]), copy-neutral LOH ([AA]), balanced amplifications ([AABB]), and allelic imbalances ([AAB] or [AAAB], etc.).
Chromosomal segments were sharply defined.
Fluorescence in situ hybridization copy numbers, as well as the high similarity between the DNA index and the allelic state index, which is the average of the allelic states across the genome, validated the method.
This new approach provides an individual molecular measure of chromosomal aberrations and will likely have repercussions for preoperative molecular staging, classification, and prognostic profiling of tumors, particularly for heterogeneous aneuploid tumors, and allows the study of the underlying molecular genetic mechanisms and clonal evolution of tumor subpopulations. | 21,291 |
Title:
Trends in the methods used for suicide in Northern Ireland.
Abstract:
As domestic gas was made less toxic in Northern Ireland during the period 1960-1988, it was used less often for suicide.
During the same period, as car ownership increased, the use of car exhaust for suicide increased in popularity without there being a corresponding decrease in the use of other methods.
Part of the temporal variation in suicide rates in Northern Ireland may be accounted for by the relative availability of lethal methods for suicide.
Language: en | 21,296 |
Title:
BEAR, a Novel Virtual Screening Methodology for Drug Discovery
Abstract:
BEAR (binding estimation after refinement) is a new virtual screening technology based on the conformational refinement of docking poses through molecular dynamics and prediction of binding free energies using accurate scoring functions.
Here, the authors report the results of an extensive benchmark of the BEAR performance in identifying a smaller subset of known inhibitors seeded in a large (1.5 million) database of compounds.
BEAR performance proved strikingly better if compared with standard docking screening methods.
The validations performed so far showed that BEAR is a reliable tool for drug discovery.
It is fast, modular, and automated, and it can be applied to virtual screenings against any biological target with known structure and any database of compounds.
(Journal of Biomolecular Screening 2011:129-133) | 21,301 |
Title:
Replication interference between human papillomavirus types 16 and 18 mediated by heterologous E1 helicases
Abstract:
BackgroundCo-infection of multiple genotypes of human papillomavirus (HPV) is commonly observed among women with abnormal cervical cytology, but how different HPVs interact with each other in the same cell is not clearly understood.
A previous study using cultured keratinocytes revealed that genome replication of one HPV type is inhibited by co-existence of the genome of another HPV type, suggesting that replication interference occurs between different HPV types when co-infected; however, molecular mechanisms underlying inter-type replication interference have not been fully explored.
MethodsReplication interference between two most prevalent HPV types, HPV16 and HPV18, was examined in HPV-negative C33A cervical carcinoma cells co-transfected with genomes of HPV16 and HPV18 together with expression plasmids for E1/E2 of both types.
Levels of HPV16/18 genome replication were measured by quantitative real-time PCR.
Physical interaction between HPV16/18 E1s was assessed by co-immunoprecipitation assays in the cell lysates.
ResultsThe replication of HPV16 and HPV18 genomes was suppressed by co-expression of E1/E2 of heterologous types.
The interference was mediated by the heterologous E1, but not E2.
The oligomerization domain of HPV16 E1 was essential for HPV18 replication inhibition, whereas the helicase domain was dispensable.
HPV16 E1 co-precipitated with HPV18 E1 in the cell lysates, and an HPV16 E1 mutant Y379A, which bound to HPV18 E1 less efficiently, failed to inhibit HPV18 replication.
ConclusionsCo-infection of a single cell with both HPV16 and HPV18 results in replication interference between them, and physical interaction between the heterologous E1s is responsible for the interference.
Heterooligomers composed of HPV16/18 E1s may lack the ability to support HPV genome replication. | 21,317 |
Title:
Verification of relationships between anthropometric variables among ureteral stents recipients and ureteric lengths: a challenge for Vitruvian-da Vinci theory
Abstract:
OBJECTIVE: To determine and verify how anthropometric variables correlate to ureteric lengths and how well statistical models approximate the actual ureteric lengths. ::: ::: MATERIALS AND METHODS: In this work, 129 charts of endourological patients (71 females and 58 males) were studied retrospectively.
Data were gathered from various research centers from North and South America.
Continuous data were studied using descriptive statistics.
Anthropometric variables (age, body surface area, body weight, obesity, and stature) were utilized as predictors of ureteric lengths.
Linear regressions and correlations were used for studying relationships between the predictors and the outcome variables (ureteric lengths); P-value was set at 0.05.
To assess how well statistical models were capable of predicting the actual ureteric lengths, percentages (or ratios of matched to mismatched results) were employed. ::: ::: RESULTS: The results of the study show that anthropometric variables do not correlate well to ureteric lengths.
Statistical models can partially estimate ureteric lengths.
Out of the five anthropometric variables studied, three of them: body frame, stature, and weight, each with a P<0.0001, were significant.
Two of the variables: age (R (2)=0.01; P=0.20) and obesity (R (2)=0.03; P=0.06), were found to be poor estimators of ureteric lengths.
None of the predictors reached the expected (match:above:below) ratio of 1:0:0 to qualify as reliable predictors of ureteric lengths. ::: ::: CONCLUSION: There is not sufficient evidence to conclude that anthropometric variables can reliably predict ureteric lengths.
These variables appear to lack adequate specificity as they failed to reach the expected (match:above:below) ratio of 1:0:0.
Consequently, selections of ureteral stents continue to remain a challenge.
However, height (R (2)=0.68) with the (match:above:below) ratio of 3:3:4 appears suited for use as estimator, but on the basis of decision rule.
Additional research is recommended for stent improvements and ureteric length determinations. | 21,336 |
Title:
Short-Term Treatment with Bisphenol-A Leads to Metabolic Abnormalities in Adult Male Mice
Abstract:
Bisphenol-A (BPA) is one of the most widespread endocrine disrupting chemicals (EDC) used as the base compound in the manufacture of polycarbonate plastics.
Although evidence points to consider exposure to BPA as a risk factor for insulin resistance, its actions on whole body metabolism and on insulin-sensitive tissues are still unclear.
The aim of the present work was to study the effects of low doses of BPA in insulin-sensitive peripheral tissues and whole body metabolism in adult mice.
Adult mice were treated with subcutaneous injection of 100 µg/kg BPA or vehicle for 8 days.
Whole body energy homeostasis was assessed with in vivo indirect calorimetry.
Insulin signaling assays were conducted by western blot analysis.
Mice treated with BPA were insulin resistant and had increased glucose-stimulated insulin release.
BPA-treated mice had decreased food intake, lower body temperature and locomotor activity compared to control.
In skeletal muscle, insulin-stimulated tyrosine phosphorylation of the insulin receptor β subunit was impaired in BPA-treated mice.
This impairment was associated with a reduced insulin-stimulated Akt phosphorylation in the Thr308 residue.
Both skeletal muscle and liver displayed an upregulation of IRS-1 protein by BPA.
The mitogen-activated protein kinase (MAPK) signaling pathway was also impaired in the skeletal muscle from BPA-treated mice.
In the liver, BPA effects were of lesser intensity with decreased insulin-stimulated tyrosine phosphorylation of the insulin receptor β subunit. ::: ::: In conclusion, short-term treatment with low doses of BPA slows down whole body energy metabolism and disrupts insulin signaling in peripheral tissues.
Thus, our findings support the notion that BPA can be considered a risk factor for the development of type 2 diabetes. | 21,445 |
Title:
Organization, structure and assembly of immunoglobulin heavy chain diversity DNA segments
Abstract:
We have identified, cloned, and sequenced eight different DNA segments encoding the diversity (D) regions of mouse immunoglobulin heavy-chain genes.
Like the two D segments previously characterized (16, 17), all eight D segments are flanked by characteristic heptamers and nonamers separated by 12-bp spacers.
These 10 D segments, and several more D segments identified but not yet sequenced, can be classified into three families based on the extent of sequence homology.
The SP2 family consists of nine highly homologous D segments that are all 17-bp long and clustered in a chromosomal region of approximately 60 kb.
The FL16 family consists of up to four D segments, two of which were mapped in the 5' end region of the SP2-D cluster.
The two FL16D segments are 23 and 17 bp long.
The third, the Q52 family, is a single-member family of the 10-bp-long DQ52, located 700 bp 5' to the JH cluster.
We argue that the D-region sequences of the majority of heavy chain genes arise from these germline D segments by various somatic mechanisms, including joining of multiple D segments.
We present a specific model of D-D joining that does not violate the 12/23-bp spacer rule. | 21,492 |
Title:
Neonatal pain and COMT Val158Met genotype in relation to serotonin transporter (SLC6A4) promoter methylation in very preterm children at school age
Abstract:
Children born very preterm are exposed to repeated neonatal procedures that induce pain and stress during hospitalization in the neonatal intensive care unit (NICU).
The COMT Val158Met genotype is involved with pain sensitivity, and early life stress is implicated in altered expression of methylation of the serotonin transporter.
We examined: (1) whether methylation of the serotonin transporter gene (SLC6A4) promoter differs between very preterm children and full-term controls at school age, (2) relationships with child behavior problems, and (3) whether the extent of neonatal pain exposure interacts with the COMT Val158Met genotype to predict SLC6A4 methylation at 7 years in the very preterm children.
We examined the associations between the COMT genotypes, neonatal pain exposure (adjusted for neonatal clinical confounders), SLC6A4 methylation and behavior problems.
Very preterm children had significantly higher methylation at 7/10 CpG sites in the SLC6A4 promoter compared to full-term controls at 7 years.
Neonatal pain (adjusted for clinical confounders) was significantly associated with total child behaviour problems on the Child Behavior Checklist (CBCL) questionnaire (adjusted for concurrent stressors and 5HTTLPR genotype) (p = 0.035).
CBCL total problems was significantly associated with greater SLC6A4 methylation in very preterm children (p = 0.01).
Neonatal pain (adjusted for clinical confounders) and COMT Met/Met genotype were associated with SLC6A4 promoter methylation in very preterm children at 7 years (p = 0.001).
These findings provide evidence that both genetic predisposition and early environment need to be considered in understanding susceptibility for developing behavioral problems in this vulnerable population. | 21,496 |
Title:
Merlin controls the repair capacity of Schwann cells after injury by regulating Hippo/YAP activity
Abstract:
Loss of the Merlin tumor suppressor and activation of the Hippo signaling pathway play major roles in the control of cell proliferation and tumorigenesis.
We have identified completely novel roles for Merlin and the Hippo pathway effector Yes-associated protein (YAP) in the control of Schwann cell (SC) plasticity and peripheral nerve repair after injury.
Injury to the peripheral nervous system (PNS) causes a dramatic shift in SC molecular phenotype and the generation of repair-competent SCs, which direct functional repair.
We find that loss of Merlin in these cells causes a catastrophic failure of axonal regeneration and remyelination in the PNS.
This effect is mediated by activation of YAP expression in Merlin-null SCs, and loss of YAP restores axonal regrowth and functional repair.
This work identifies new mechanisms that control the regenerative potential of SCs and gives new insight into understanding the correct control of functional nerve repair in the PNS. | 21,520 |
Title:
Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995–2007 (the International Cancer Benchmarking Partnership): an analysis of population-based cancer registry data
Abstract:
Summary Background Cancer survival is a key measure of the effectiveness of health-care systems.
Persistent regional and international differences in survival represent many avoidable deaths.
Differences in survival have prompted or guided cancer control strategies.
This is the first study in a programme to investigate international survival disparities, with the aim of informing health policy to raise standards and reduce inequalities in survival.
Methods Data from population-based cancer registries in 12 jurisdictions in six countries were provided for 2·4 million adults diagnosed with primary colorectal, lung, breast (women), or ovarian cancer during 1995–2007, with follow-up to Dec 31, 2007.
Data quality control and analyses were done centrally with a common protocol, overseen by external experts.
We estimated 1-year and 5-year relative survival, constructing 252 complete life tables to control for background mortality by age, sex, and calendar year.
We report age-specific and age-standardised relative survival at 1 and 5 years, and 5-year survival conditional on survival to the first anniversary of diagnosis.
We also examined incidence and mortality trends during 1985–2005.
Findings Relative survival improved during 1995–2007 for all four cancers in all jurisdictions.
Survival was persistently higher in Australia, Canada, and Sweden, intermediate in Norway, and lower in Denmark, England, Northern Ireland, and Wales, particularly in the first year after diagnosis and for patients aged 65 years and older.
International differences narrowed at all ages for breast cancer, from about 9% to 5% at 1 year and from about 14% to 8% at 5 years, but less or not at all for the other cancers.
For colorectal cancer, the international range narrowed only for patients aged 65 years and older, by 2–6% at 1 year and by 2–3% at 5 years.
Interpretation Up-to-date survival trends show increases but persistent differences between countries.
Trends in cancer incidence and mortality are broadly consistent with these trends in survival.
Data quality and changes in classification are not likely explanations.
The patterns are consistent with later diagnosis or differences in treatment, particularly in Denmark and the UK, and in patients aged 65 years and older.
Funding Department of Health, England; and Cancer Research UK. | 21,755 |
Title:
Sanitization efficacy of anaerobic digestion and aeration of slurry from the aspect of limiting emission of Salmonella into the environment.
Abstract:
The aim of this study was to estimate the usefulness of mesophilic anaerobic digestion and aeration for sanitization of slurry from the aspect of limiting transmission of Salmonella into the environment.
Material for the study was fresh pig slurry.
Collected samples were subjected to anaerobic digestion at 35°C and aeration with an initial temperature of 35°C.
The efficacy of both methods was examined based on determination of the elimination rate and theoretical time of survival of Salmonella Senftenberg W(775), Salmonella Enteritidis and Salmonella Typhimurium introduced into slurry in carriers of type Filter-Sandwich.
Samples for the study were collected every 24 hours and the number of bacilli was determined with the MPN (Most Probably Number) method.
The study indicated that fermentation is a more effective method for slurry sanitization.
A higher rate of elimination and shorter time of survival of all the tested bacteria was observed, compared with the use of aeration.
The experiment allowed us to prove the high sanitization efficacy of both examined methods.
They ensure the full elimination of the tested serotypes of Salmonella in only slightly more than 10 days.
The use of fermentation or aeration as a way of slurry treatment for agricultural purposes makes it possible to obtain a fertilizer which is valuable and safe for humans and the environment. | 21,765 |
Title:
Anti-Mullerian Hormone: Above and Beyond Conventional Ovarian Reserve Markers
Abstract:
Management of ovarian dysfunctions requires accurate estimation of ovarian reserve (OR).
Therefore, reproductive hormones and antral follicle count (AFC) are assessed to indicate OR.
Serum anti-Mullerian hormone (AMH) is a unique biomarker that has a critical role in folliculogenesis as well as steroidogenesis within ovaries.
Secretion from preantral and early antral follicles renders AMH as the earliest marker to show OR decline.
In this review we discuss the dynamics of circulating AMH that remarkably vary with sex and age.
As it emerges as a marker of gonadal development and reproductive disorders, here we summarize the role of AMH in female reproductive physiology and provide evidence of higher accuracy in predicting ovarian response to stimulation.
Further, we attempt to compile potential clinical applications in children and adults.
We propose that AMH evaluation has a potential role in effectively monitoring chemotherapy and pelvic radiation induced ovarian toxicity.
Furthermore, AMH guided ovarian stimulation can lead to individualization of therapeutic strategies for infertility treatment.
However future research on AMH levels within follicular fluid may pave the way to establish it as a marker of "quality" besides "quantity" of the growing follicles. | 21,781 |
Title:
Perceptions, Barriers, and Suggestions for Creation of a Tobacco and Health Website Among American Indian/Alaska Native College Students
Abstract:
Information concerning American Indian/Alaska Native (AI/AN) Internet use and health information needs is dearth.
Our research team explored Internet use among AI/AN college students to determine Internet use in relation to health information seeking behaviors.
We used a tobacco site example for participants to describe what they desired in a health site designed specifically for AI/AN.
Using a community-based participatory research approach, we conducted 14 focus groups with AI/AN college students (N = 108), to better understand their perceptions of and attitudes toward Internet use and health information needs.
Daily Internet use was reported across strata yet health topics investigated differed among groups.
Participants in all strata desired a health website that was easy to navigate and interactive.
Respectful representation of Native culture was a concern, yet no consensus was reached for a multi-tribal audience.
Participants felt a website should use caution with cultural depictions due to the possible misinterpretation.
Overall, participants agreed that recreational and traditional tobacco use should be differentiated and the variation of traditional use among tribes acknowledged.
Data concerning Internet use for health information among AI/AN college students are needed to establish baseline indicators to effectively address disparities. | 21,817 |
Title:
Extracting depth information of 3-dimensional structures from a single-view X-ray Fourier-transform hologram
Abstract:
We demonstrate how information about the three-dimensional structure of an object can be extracted from a single Fourier-transform X-ray hologram.
In contrast to lens-based 3D imaging approaches that provide depth information of a specimen utilizing several images from different angles or via adjusting the focus to different depths, our method capitalizes on the use of the holographically encoded phase and amplitude information of the object’s wavefield.
It enables single-shot measurements of 3D objects at coherent X-ray sources.
As the ratio of longitudinal resolution over transverse resolution scales proportional to the diameter of the reference beam aperture over the X-ray wavelength, we expect the approach to be particularly useful in the extreme ultraviolet and soft-X-ray regime. | 21,863 |
Title:
Deficit of social cognition in subjects with surgically treated frontal lobe lesions and in subjects affected by schizophrenia
Abstract:
The ability of humans to predict and explain other people’s behaviour by attributing independent mental states such as desires and beliefs to them, is considered to be due to our ability to construct a “Theory of Mind”.
Recently, several neuroimaging studies have implicated the medial frontal lobes as playing a critical role in a dedicated “mentalizing” or “Theory of Mind” network in the human brain.
In this study we compare the performance of patients with right and left medial prefrontal lobe lesions in theory of mind and in social cognition tasks, with the performance of people with schizophrenia.
We report a similar social cognitive profile between patients with prefrontal lobe lesions and schizophrenic subjects in terms of understanding of false beliefs, in understanding social situations and in using tactical strategies.
These findings are relevant for the functional anatomy of “Theory of Mind”. | 21,891 |
Title:
Plasma homocysteine, methylene tetrahydrofolate reductase C677T and factor II G20210A polymorphisms, factor VIII, and VWF in central retinal vein occlusion
Abstract:
AIMS To determine whether plasma homocysteine, methylene tetrahydrofolate reductase (MTHFR) C677T and factor II G20210A polymorphisms, factor VIII, and vWF are risk factors for central retinal vein occlusion (CRVO).
METHOD Prospective comparison of 63 consecutive patients with central retinal vein occlusion and 63 age matched controls.
Plasma homocysteine and vWF were estimated by ELISA, the MTFHR and factor II G20210A polymorphisms determined by polymerase chain reaction with restriction enzyme product digestion and factor VIII by one stage automated clotting assay.
RESULTS Plasma homocysteine (patients: median 12.4 μmol/l, controls: median 11.6 μmol OR = 1.05, p=0.20), factor VIII (patients: median = 115 U/dl, controls: median = 113 U/dl), and vWF (patients: median = 115 U/dl, controls: median = 108 U/dl) were not statistically higher in patients than in controls.
Five CRVO patients and seven controls were homozygous for the MTHFR C677T mutation.
One control was heterozygous for the factor II G20210A mutation.
CONCLUSION This study has not identified new risk factors for CRVO. | 21,897 |
Title:
Gender, body mass index and socio-demographic variables associated with knowledge about type 2 diabetes mellitus among 13 293 Mexican students
Abstract:
The main aim of this study was to evaluate correlates of the knowledge Mexican young people have about type 2 diabetes mellitus (DM) risk and prevention.
We developed a cross-sectional study in public schools in Morelos, in central Mexico during 1998-1999 in 13,293 students (11-24 years).
We determined body mass index (BMI) with anthropometric measurements (height and weight).
Using questionnaire data, we constructed a DM knowledge-based scale.
Statistical analysis was done using an ordinal, logistic regression model.
Only 1.6% of the students (95%CI = 1.4-1.8) had high DM knowledge levels; 85.6% (95%CI = 84.9-86.1) had low levels.
The factors with the strongest associations with high levels of knowledge about type 2 DM among the Mexican students in this study were: being in high school or at university (vs. junior high), urban residence, higher socio-economic level, and BMI indicating overweight or obesity.
Other socio-demographic factors correlated with high levels of knowledge about the disease, but with slightly weaker associations, included female gender, higher age, higher academic achievement (grades) and higher education level of the student's mother.
While young men who were overweight or obese were 2.6 and 3.4 times more likely to have high levels of knowledge about DM (95%CI = 1.9-3.6 and 2.1-5.5, respectively), young women who were overweight or obese were only 1.4 and 1.1 times more likely to have high knowledge about DM (95%CI = 1.0-1.9 and 0.6-1.8, respectively).
Mexican young people have limited knowledge about DM, although this chronic disease is increasingly common in Mexico as in many other countries. | 21,900 |
Title:
Induction of Interleukin 10–Producing, Nonproliferating Cd4+ T Cells with Regulatory Properties by Repetitive Stimulation with Allogeneic Immature Human Dendritic Cells
Abstract:
The functional properties of dendritic cells (DCs) are strictly dependent on their maturational state.
To analyze the influence of the maturational state of DCs on priming and differentiation of T cells, immature CD83− and mature CD83+ human DCs were used for stimulation of naive, allogeneic CD4+ T cells.
Repetitive stimulation with mature DCs resulted in a strong expansion of alloreactive T cells and the exclusive development of T helper type 1 (Th1) cells.
In contrast, after repetitive stimulation with immature DCs the alloreactive T cells showed an irreversibly inhibited proliferation that could not be restored by restimulation with mature DCs or peripheral blood mononuclear cells, or by the addition of interleukin (IL)-2.
Only stimulation of T cells with mature DCs resulted in an upregulation of CD154, CD69, and CD70, whereas T cells activated with immature DCs showed an early upregulation of the negative regulator cytotoxic T lymphocyte–associated molecule 4 (CTLA-4).
These T cells lost their ability to produce interferon γ, IL-2, or IL-4 after several stimulations with immature DCs and differentiated into nonproliferating, IL-10–producing T cells.
Furthermore, in coculture experiments these T cells inhibited the antigen-driven proliferation of Th1 cells in a contact- and dose-dependent, but antigen-nonspecific manner.
These data show that immature and mature DCs induce different types of T cell responses: inflammatory Th1 cells are induced by mature DCs, and IL-10–producing T cell regulatory 1–like cells by immature DCs. | 22,000 |
Title:
EGFR kinase inhibitors and gastric acid suppressants in EGFR-mutant NSCLC: a retrospective database analysis of potential drug interaction
Abstract:
// Nesaretnam Barr Kumarakulasinghe 1, * , Nicholas Syn 1, 2, 3, * , Yu Yang Soon 4 , Atasha Asmat 5 , Huili Zheng 6 , En Yun Loy 6 , Brendan Pang 2, 7 , Ross Andrew Soo 1, 2 1 Department of Haematology-Oncology, National University Cancer Institute, Singapore 2 Cancer Science Institute of Singapore, National University of Singapore, Singapore 3 Yong Loo Lin School of Medicine, National University of Singapore, Singapore 4 Department of Radiation Oncology, National University Cancer Institute, Singapore 5 Department of General Surgery, Tan Tock Seng Hospital, Singapore 6 National Registry of Diseases Office, Health Promotion Board, Singapore 7 Department of Pathology, National University Health System, Singapore * These authors have contributed equally to this work as co-first authors Correspondence to: Ross Andrew Soo, email: [email protected] Keywords: gefitinib, erlotinib, drug-drug interactions, NSCLC, gastric acid suppression Received: August 19, 2016 Accepted: October 27, 2016 Published: November 19, 2016 ABSTRACT Background: Erlotinib and gefitinib are weak base drugs whose absorption and clinical efficacy may be impaired by concomitant gastric acid suppressive (AS) therapy, yet proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2As) are widely indicated in non-small cell lung cancer (NSCLC) patients for the prevention and treatment of erlotinib-induced gastrointestinal injury and corticosteroid-associated gastric irritation.
We assessed the clinical relevance of this potential drug-drug interaction (DDI) in a retrospective cohort of EGFR -mutant NSCLC patients.
Results: The AS usage rate was 35%.
In the overall cohort, AS users did not experience poorer OS (HR: 1.47, 95% CI: 0.92 – 2.35, P = 0.10; median, 11.4 versus 17.5 months) or PFS (HR = 1.37, 95% CI: 0.89 – 2.12, P = 0.16; median, 7.6 versus 8.7 months) compared with non-users in multivariate Cox regression analysis.
However, subgroup analyses indicated that AS usage was associated with significantly poorer OS and PFS in patients who had fewer or milder comorbidities (Charlson comorbidity index ≤ 2), those with Karnofsky performance status < 90, and never-smokers.
Materials and Methods: A retrospective database analysis of 157 patients given erlotinib or gefitinib for EGFR -mutant advanced NSCLC from two institutions was conducted.
Patients were classified as AS-users if the periods of AS and anti-EGFR therapy overlapped by ≥ 30%.
Overall survival (OS) and progression-free survival (PFS) were assessed according to AS usage.
Conclusions: Concomitant AS therapy did not have an adverse impact on OS and/or PFS in the overall cohort.
Our subgroup findings should be regarded exploratory and require replication in a large prospective cohort. | 22,082 |
Title:
Identification of an AID-independent pathway for chromosomal translocations between the Igh switch region and Myc
Abstract:
Chromosomal translocations involving immunoglobulin heavy chain (Igh) switch regions and an oncogene such as Myc represent initiating events in the development of many B cell malignancies.
These translocations are widely thought to result from aberrant class-switch recombination.
To test this model, we measured translocations in mice deficient in activation-induced cytidine deaminase (AID) that lack class-switch recombination.
We found that AID made no measurable contribution to the generation of initial translocations, indicating that the intrinsic fragility of the switch regions or a pathway unrelated to AID is responsible for these translocations.
In contrast, the outgrowth of translocation-positive cells was dependent on AID, raising the possibility that AID is important in tumor progression, perhaps by virtue of its mutagenic properties. | 22,211 |
Title:
Variation in Antimicrobial Utilization for Febrile Neutropenia in Cancer Patients
Abstract:
Background: No previous study has compared hospitals with respect to the variation of antimicrobial utilization (AU) for cancer patients with febrile neutropenia (FNE).
Patients and Methods: We conducted an observational cohort study, carried out in 18 tertiary care centers across nine countries, in order to describe AU patterns for cancer patients with FNE and to evaluate whether prescription was appropriate.
Results: A total of 148 patients was exposed to 483 antimicrobial agents and 318 therapeutic courses, corresponding to 1,766 antimicrobial exposure-days.
The most frequently used initial treatment consisted of a combination of a broad-spectrum β-lactam agent and an aminoglycoside (50%).
The extent of initial monotherapy varied between 5% in German and 30% in French centers.
Glycopeptides, fluconazole and acyclovir were incorporated into initial empiric therapy in 21, 13 and nine instances, respectively.
The French centers prescribed the largest number of antimicrobial courses per FNE (mean 2.5 ± 1.5), whereas the center with the highest antimicrobial exposure density was observed in the USA (2.8 exposure-days per 1 FNE-day).
AU was judged to be inappropriate by at least one criterion in 59 patients (40%).
Conclusion: This pilot study revealed important variation in AU intensity and prescription preferences in FNE patients and may help to develop appropriate strategies to improve antimicrobial therapy for this patient population. | 22,368 |
Title:
Postprandial GLP-1, Norepinephrine, and Reactive Hypoglycemia in Dumping Syndrome
Abstract:
Rapid gastric emptying and exaggerated plasma concentrations of the insulinotropic hormone GLP-1 precede reactive hypoglycemia after oral glucose in gastrectomy patients.
We suspected that the plasma volume drop associated with rapid gastric emptying (early dumping) would be accompanied by elevated plasma concentrations of norepinephrine.
In order to study any relationship between postprandial norepinephrine, the enteroinsular axis, and plasma glucose, twelve patients with dumping syndrome and nine controls were studied.
The plasma concentrations of norepinephrine, GLP-1, GIP, glucagon, insulin, and glucose were measured following a 1.5 g/kg lean body mass glucose meal.
The early (0–30 min) integrated norepinephrine concentration was significantly higher in dumpers (22.1 ± 3.8 nmol/ml/min) compared to controls (14.7 ± 3.1 nmol/ml/min; P < 0.001) and correlated closely with the postprandial hematocrit increment (r = 0.71; P < 0.05).
Early immunoreactivities of GLP-1, GIP, and glucagon peaked 30 min after glucose ingestion and were significantly higher in dumpers.
Insulin peaked after 60 min and correlated with early GLP-1.
In 11 of the patients glucose fell below baseline after a median interval of 120 min.
Glucose at 120 min, when most of the nadirs occurred was lowest in patients with high early GLP-1 concentrations (r = 0.78; P < 0.001).
Gel filtration chromatography of the dumpers' plasma revealed that pancreatic glucagon was detectable at time 0 and after 20 min, but not after 120 min.
It is concluded that in dumpers pancreatic glucagon is augmented in the early postprandial period, probably through stimulation by catecholamines.
At 120 min, when most of the hypoglycemias are encountered, pancreatic glucagon is no longer detectable, probably through inhibition by GLP-1. | 22,393 |
Title:
Type beta transforming growth factor in human platelets: release during platelet degranulation and action on vascular smooth muscle cells
Abstract:
A specific radioimmunoassay for type beta transforming growth factor (TGF-beta) was developed and used to show that human platelets treated with thrombin release TGF-beta as a consequence of degranulation.
The thrombin concentrations required to induce release of TGF-beta parallel those concentrations that release the alpha-granule marker, beta-thromboglobulin.
Related studies showed that TGF-beta acts on early passage, explant cultures of bovine aortic smooth muscle cells by inhibiting the effect of mitogens on proliferation of subconfluent cell monolayers yet synergizing with mitogens to stimulate growth of the same cells when cultured in soft agar.
The results show that primary cultures of bovine aortic smooth muscle cells and established normal rat kidney cells behave similarly with regard to TGF-beta action.
Moreover, the data suggest that platelet-mediated proliferation of aortic smooth muscle cells in vivo may not result solely from the stimulatory effect of platelet-derived growth factor (PDGF), but rather from an interaction of platelet factors which has the intrinsic ability to limit as well as stimulate mitosis. | 22,524 |
Title:
Pitfalls of genetic analysis using a doubled-haploid backcrossed to its parent
Abstract:
A population derived from a doubled-haploid backcrossed to its parent has a unique genetic structure, which affects the mapping and genetic analysis of molecular-marker data.
In such a cross: (1) repulsion linkages are reduced dramatically and can be detected only in restricted chromosome sections; each repulsion-linkage group represents a section of a chromosome carrying a crossover that occurred in the meiosis that produced the gamete from which the doubled-haploid was derived; (2) the number of coupling-linkage groups observed depends on how many crossovers occurred during the meiosis; the observed size of a linkage group will be only a fraction of a total chromosome if the chromosome carried in the doubled-haploid resulted from crossover exchanges; (3) the size covered by all the observed linkages is only equivalent to the haploid genome; and (4) the ratio of single-dose to multi-dose markers is inflated.
These features have not been recognized in previous reports, resulting in misinterpretations in genetic mapping and analysis of the molecular-marker data.
The ratio of single- to multi-dose markers has been used inappropriately to distinguish polyploid type. | 22,527 |
Title:
Scavenging on a pulsed resource: quality matters for corvids but density for mammals
Abstract:
Human food subsidies can provide predictable food sources in large quantities for wildlife species worldwide.
In the boreal forest of Fennoscandia, gut piles from moose (Alces alces) harvest provide a potentially important food source for a range of opportunistically scavenging predators.
Increased populations of predators can negatively affect threatened or important game species.
As a response to this, restrictions on field dressing of moose are under consideration in parts of Norway.
However, there is a lack of research to how this resource is utilized.
In this study, we used camera-trap data from 50 gut piles during 1043 monitoring days.
We estimated depletion of gut piles separately for parts with high and low energy content, and used these results to scale up gut pile density in the study area.
We identified scavenger species and analyzed the influences of gut pile quality and density on scavenging behavior of mammals and corvids (family Corvidae).
Main scavengers were corvids and red fox (Vulpes vulpes).
Parts with high energy content were rapidly consumed, mainly by corvids that were present at all gut piles shortly after the remains were left at the kill site.
Corvid presence declined with days since harvest, reflecting reduction in gut pile quality over time independent of gut pile density.
Mammals arrived 7–8 days later at the gut piles than corvids, and their presence depended only on gut pile density with a peak at intermediate densities.
The decline at high gut pile densities suggest a saturation effect, which could explain accumulation of gut pile parts with low energy content.
This study shows that remains from moose harvest can potentially be an important food resource for scavengers, as it was utilized to a high degree by many species.
This study gives novel insight into how energy content and density of resources affect scavenging patterns among functional groups of scavengers. | 22,583 |
Title:
Is a FAN Always FUN? Phonological and Orthographic Effects in Bilingual Visual Word Recognition
Abstract:
A visual semantic categorization task in English was performed by native English speakers (Experiment 1) and late bilinguals whose first language was Japanese (Experiment 2) or Spanish (Experiment 3).
In the critical conditions, the target word was a homophone of a correct category exemplar (e.g., A BODY OF WATER—SEE; cf. SEA) or a word that differed from the correct exemplar by a phonological contrast absent in the bilinguals’ first language (e.g., USED FOR COOLING DOWN—FUN; cf.
FAN).
Homophones elicited more false positive errors and slower processing than spelling controls in all groups.
The Japanese—English bilinguals, but not the Spanish—English bilinguals, also displayed ‘near-homophone’ effects (i.e., homophone-like effects from minimal pairs on nonnative contrasts).
We conclude that second-language visual word recognition is influenced by first-language phonology, although the effect is conditioned by the first-language orthographic system.
Near-homophone effects can occur when the orthographic sy... | 22,605 |
Title:
Retrograde Endovascular Treatment of Internal Iliac Aneurysm in a Patient with Marfan Syndrome
Abstract:
To report a technique to maintain pelvic flow to an internal iliac artery (IIA) with aneurysm in a patient with Marfan syndrome, and previously treated by infrarenal abdominal aortic aneurysm open procedure.
Retrograde endovascular hypogastric artery preservation (REHAP) through flexible endograft implantation from external iliac artery (EIA) to internal iliac artery (IIA) was used.
REHAP was a reasonable, minimally invasive and elegant alternative (new) to maintain pelvic arterial flow in Marfan syndrome.
However, the long-term durability is unknown, and so, it should be used in selected patients. | 22,646 |
Title:
An efficient method for computing steady state solutions with Gillespie’s direct method
Abstract:
Gillespie’s direct method is a stochastic simulation algorithm that may be used to calculate the steady state solution of a chemically reacting system.
Recently the all possible states method was introduced as a way of accelerating the convergence of the simulations.
We demonstrate that while the all possible states (APS) method does reduce the number of required trajectories, it is actually much slower than the original algorithm for most problems.
We introduce the elapsed time method, which reformulates the process of recording the species populations.
The resulting algorithm yields the same results as the original method, but is more efficient, particularly for large models.
In implementing the elapsed time method, we present robust methods for recording statistics and empirical probability distributions.
We demonstrate how to use the histogram distance to estimate the error in steady state solutions. | 23,018 |
Title:
Zebra sign of precentral gyri in amyotrophic lateral sclerosis: A novel finding using phase difference enhanced (PADRE) imaging-initial results
Abstract:
OBJECTIVE ::: We compared the precentral gyri (PG) on the PADRE of patients with amyotrophic lateral sclerosis (ALS) and healthy subjects (HSs) in order to determine whether it is possible to discriminate between ALS patients and HSs on an individual basis. ::: ::: ::: METHODS ::: First, two radiologists reviewed the appearance of the normal PG and that of ALS patients on PADRE in a non-blinded manner, and deviations from the appearance of the normal PG were recorded.
Next, based on the presence of PG abnormalities on PADRE, we performed an observer performance study using 16 ALS patients and 16 HSs.
::: ::: ::: RESULTS ::: The radiologists were able to consensually define the PG as abnormal on PADRE when a low-signal-intensity layer was observed in the gray matter of the PG; a three- or four-layer organization (zebra sign) was characterized by the low-signal-intensity layer.
The observer performance study demonstrated that the sensitivity, specificity, and accuracy of PG abnormalities on PADRE for discriminating ALS patients from HSs were 94 %, 94 %, and 94 %, respectively, for reviewers 1 and 2. ::: ::: ::: CONCLUSIONS ::: It was possible to discriminate between ALS patients and HSs based on the presence of PG abnormalities on PADRE, which may reflect upper motor neuron impairment in ALS.
::: ::: ::: KEY POINTS ::: • PADRE reveals low-signal-intensity layer in the PG of ALS • By PADRE findings on PG, we can discriminate ALS from HSs • PADRE may be a useful method for detecting UMN impairment in ALS. | 23,056 |
Title:
Bcl10 links saturated fat overnutrition with hepatocellular NF-kB activation and insulin resistance.
Abstract:
Excess serum free fatty acids (FFAs) are fundamental to the pathogenesis of insulin resistance.
With high-fat feeding, FFAs activate NF-kB in target tissues, initiating negative crosstalk with insulin signaling.
However, the mechanisms underlying FFA-dependent NF-kB activation remain unclear.
Here, we demonstrate that the saturated FA, palmitate, requires Bcl10 for NF-kB activation in hepatocytes.
Uptake of palmitate, metabolism to diacylglycerol, and subsequent activation of protein kinase C (PKC) appear to mechanistically link palmitate with Bcl10, known as a central component of a signaling complex that, along with CARMA3 and MALT1, activates NF-kB downstream of selected cell surface receptors.
Consequently, Bcl10-deficient mice are protected from hepatic NF-kB activation and insulin resistance following brief high-fat diet, suggesting that Bcl10 plays a major role in the metabolic consequences of acute overnutrition.
Surprisingly, while CARMA3 also participates in the palmitate response, MALT1 is completely dispensable, thereby revealing an apparent nonclassical role for Bcl10 in NF-kB signaling. | 23,136 |
Title:
Influence of pectin and glucose on growth and polygalacturonase production by Aspergillus niger in solid-state cultivation
Abstract:
The solid-state production of endo- and exo-polygalacturonases (PG) by Aspergillus niger was studied in a media containing wheat bran, salts, and different citric pectin and/or glucose concentrations.
Kinetic analysis of the process indicated that the formation of PG and the growth of A. niger are associated processes.
By increasing citric pectin from 0 to 16% (w/w), the maximum A. niger concentration (X m) was raised from 94 to 121 mg/g dry medium suggesting that pectin can be used by A. niger as a growth substrate besides its role as an inducer.
With 16% (w/w) pectin, 281 U exo-PG/gdm and 152 U endo-PG/gdm were obtained.
Otherwise, pectin concentrations from 20 to 30% (w/w) hindered both production and growth.
A. niger concentrations of 108–113 mg/gdm were achieved in runs with glucose from 5 to 12% (w/w), whereas at 16 and 20% (w/w) glucose, lower X m values (ca. 100 mg/gdm) were measured.
The addition of glucose to the wheat bran medium, up to 10% (w/w) led to maximum endo-PG titers slightly lower than those found in the absence of glucose.
Nevertheless, exo-PG formation in these media was strongly increased and activities over 370 U/gdm were achieved.
The results suggest that in experiments with pectin concentrations until 16% (w/w), exo-PG production was repressed by pectin-degradation products although these same substances had favored biomass growth.
When glucose concentrations over 10% (w/w) were added to the media, the maximum activities of both enzymes decreased drastically, suggesting that glucose at high concentrations also exerts a repressive effect on PG production. | 23,204 |
Title:
Relative Hypo- and Hypercortisolism Are Both Associated with Depression and Lower Quality of Life in Bipolar Disorder: A Cross-Sectional Study
Abstract:
BACKGROUND ::: Depression in unipolar and bipolar disorders is associated with hypothalamic-pituitary-adrenal-axis (HPA-axis) hyperactivity.
Also, unipolar disorder has recently been shown to exhibit HPA-axis hypoactivity.
We studied for the first time how HPA-axis hypo- and hyperactivity relate to depression and disease burden in bipolar disorder.
We were interested in studying hypocortisolism; characterized by increased HPA-axis negative feedback sensitivity and lower basal cortisol levels together with the opposite HPA-axis regulatory pattern of hypercortisolism.
::: ::: ::: METHODS ::: This cross-sectional study includes 145 type 1 and 2 bipolar outpatients and 145 matched controls.
A dexamethasone-suppression-test (DST) measures the negative feedback sensitivity and a weight-adjusted very-low-dose DST was employed, which is sensitive in identifying hypocortisolism and hypercortisolism.
The 25th and 75th percentiles of control post-DST values were used as cut-offs identifying patients exhibiting relative hypo-, and hypercortisolism.
Self-report questionnaires were employed: Beck-Depression-Inventory (BDI), Montgomery-Åsberg-Depression-Rating-Scale (MADRS-S), World-Health-Organization-Quality-of-Life-Assessment-100 and Global-Assessment-of-Functioning. ::: ::: ::: RESULTS ::: Patients exhibiting relative hypocortisolism expectedly exhibited lowered basal cortisol levels (p = 0.046).
Patients exhibiting relative hypercortisolism expectedly exhibited elevated basal levels (p<0.001).
Patients exhibiting relative hypocortisolism showed 1.9-2.0 (BDI, p = 0.017, MADRS-S, p = 0.37) and 6.0 (p<0.001) times increased frequencies of depression and low overall life quality compared with patients exhibiting mid post-DST values (eucortisolism).
Adjusted Odds Ratios (OR:s) for depression ranged from 3.8-4.1 (BDI, p = 0.006, MADRS-S, p = 0.011) and was 23.4 (p<0.001) for life quality.
Patients exhibiting relative hypercortisolism showed 1.9-2.4 (BDI, p = 0.017, MADRS-S, p = 0.003) and 4.7 (p<0.001) times higher frequencies of depression and low overall life quality compared with patients exhibiting eucortisolism.
Adjusted OR:s for depression ranged from 2.2-2.7 (BDI, p = 0.068, MADRS-S, p = 0.045) and was 6.3 (p = 0.008) for life quality. ::: ::: ::: LIMITATIONS ::: The cross-sectional design and lack of pre-established reference values of the DST employed. ::: ::: ::: CONCLUSIONS ::: Relative hypocortisolism and relative hypercortisolism were associated with depression and lower life quality, providing novel insights into the detrimental role of stress in bipolar disorder. | 23,232 |
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