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Category: GPR35
Background Botulinum neurotoxin type A, an FDA-approved prophylactic drug for chronic
Background Botulinum neurotoxin type A, an FDA-approved prophylactic drug for chronic migraine, is thought to achieve its restorative effect through blocking activation of unmyelinated meningeal nociceptors and their downstream communications with myelinated nociceptors and potentially the vasculature and defense cells. In feminine rats, replies to cortical dispersing unhappiness had been even more extended and typically, in some full cases, started at much longer latencies post-cortical dispersing unhappiness fairly, than have been seen in prior research in male rats. Extracranial administration of botulinum neurotoxin type A lower life expectancy the extended firing from the meningeal nociceptors considerably, in the mixed test of C-fiber and A-, however, not their response possibility. Discussion The results claim that the system of action where botulinum neurotoxin type A stops migraine change from the one where calcitonin gene-related peptide monoclonal antibodies prevent migraine which even when the foundation of migraine is normally central (i.e. in the cortex), a performing medication may intercept/prevent the headaches peripherally. strong course="kwd-title" Keywords: Migraine, headaches, botox, CGRP, trigeminal, discomfort Introduction Migraine can be a complex mind disorder, seen as a extreme and long-lasting throbbing head aches, that generally is considered to originate in irregular working of multiple mind areas and neuronal pathways that control homeosthesis, sensory, autonomic, affective and cognitive features (1,2). As the mechanisms where irregular functioning of the mind provides rise to the initial understanding of migraine headaches is largely unfamiliar, it is broadly accepted how the headache starts with activation of nociceptors supplying the meninges which drugs that avoid the activation of the nociceptors could be effective in reducing migraine. OnabotulinumtoxinA (BoNT-A) can be an FDA-approved prophylactic medication for chronic migraine (3,4). When useful for migraine avoidance, BoNT-A can be injected into discrete pericranial, throat and shoulder muscle groups (5). Until lately, it was not yet determined how administration of BoNT-A to peripheral sites beyond your comparative mind decreases the level of sensitivity, responsiveness or activity of nociceptors providing the meninges, inside the head. A significant advance in answering this question was made by the discovery of two populations of sensory fibers that cross the bones of the calvaria, one originating in the trigeminal ganglion and crossing from inside to outside through sutures of the calvaria (i.e. belonging to the trigeminovascular pathway) (6C8), and a second originating in C2-C3 dorsal root ganglia and crossing from outside to inside through small foramen and emissary canals (i.e. belonging to the cervicovascular pathway) (9). Our overall understanding of the mechanism of action of BoNT-A derives from its ability to disrupt sensory transmission by preventing the adhesion of synaptic vesicles to the synaptic membrane and consequently the release of neurotransmitters and/or insertion of membrane-bound ion channels and receptors (10). For reasons that are not yet understood, BoNT-A appears to inhibit unmyelinated C- also to a much lesser extent myelinated A-nociceptors mainly. This conclusion was initially reached in some elegant research of cutaneous nociceptors (11C14), and later on seen in research of meningeal nociceptors (16). When given towards the dura topically, BoNT-A decreased considerably the mechanosensitivity of C- however, not A-meningeal nociceptors and reversed their sensitization by inflammatory mediators (15). When injected seven days previously extracranially, BoNT-A reduced the occurrence and magnitude Vargatef biological activity of activation of C- however, not A-meningeal nociceptors by TRPV1 and TRPA1 agonists (16). Common to these scholarly research was that the used stimuli had been all given locally/topically to the exterior, instead of inside Vargatef biological activity layer from the dura (i.e. beyond your blood brain hurdle (bbb)) which their administration modeled intracranial nociception (we.e. long term activation of meningeal nociceptors) instead of migraine. One of the most popular and greatest characterized animal types of migraine may be the induction of cortical growing melancholy (CSD) (17). CSD is a slowly Vargatef biological activity propagating wave of neuronal depolarization thought to underlie the aura phase of migraine (18). Because CSD is an event that occurs inside the bbb, our previous studies KCTD19 antibody could not predict the effects of extracranial administration of BoNT-A on activation of meningeal nociceptors by CSD. To better understand BoNT-A mechanisms of action in migraine prevention, in the current study we injected rats with BoNT-A and 7 days later determined the extent of activation of C- and A meningeal nociceptors by CSD. Methods and Components BoNT-A suture.
Posted on July 3, 2020 by bioentryplusPosted in GPR35Tagged KCTD19 antibody, Vargatef biological activity
Supplementary MaterialsSupplementary Desk S1 mmc1. tumor tissue and matched up normal
Supplementary MaterialsSupplementary Desk S1 mmc1. tumor tissue and matched up normal lung tissue and demonstrated the current presence of specific T cell immune system microenvironments in lung tumor patients. strong course="kwd-title" Keywords: Adaptive immune system response, T cell receptor repertoire, Lung tumor, High-throughput sequencing, TCR variety Introduction Adaptive immune system replies against tumors are guaranteeing prognostic indications for multiple malignancies [1]. T cells infiltrating the tumor microenvironment and their matching receptors play essential jobs in adaptive immune system replies. T cell replies to tumor cells depend generally in AZD6738 ic50 the affinity between T cell receptors (TCRs) and peptide-major histocompatibility complicated (pMHC). Maintaining and Developing highly varied TCR repertoires to guard against numerous foreign pathogens is demanding [2]. TCRs are heterodimers made up of either particular and chains, representing the most frequent types of TCRs, or particular and chains. TCR variety is seen as a recombination from the V/J gene sections from the TCR and V/D/J gene sections from the TCR. The recombination especially occurs in complementarity identifying area 3 (CDR3) area of TCR [3], [4]. As a result, characterizing the bond between tumor cells as well as the web host adaptive disease fighting capability, especially pertaining to the Mouse monoclonal to STAT5B TCR CDR3 domain name, is vital for understanding tumor immunology, particularly for identifying therapeutic targets and monitoring immunotherapy responses [5]. The development of next-generation sequencing (NGS) technologies has enabled detailed profiling of the immune system. Recently, advancements in platforms have facilitated the analysis of the TCR repertoire [6], especially TCR CDR3 sequencing, making it possible to track dominant TCR clones in different tissues over time [7], [8], [9]. Tumor heterogeneity at the genetic level is often connected with strong diversity in tumor infiltrating lymphocytes (TILs) within tumor lesions [10], [11]. The clonal TIL composition can be assessed by analyzing their TCR repertoires [12]. Accordingly, studies around the AZD6738 ic50 spatial heterogeneity of TILs have been reported to elucidate the adjustments in intratumoral and peripheral T cells in a number of malignancies, including renal cell carcinoma [13], esophageal squamous cell carcinoma [14], principal liver organ carcinoma [15], and lung adenocarcinoma [16]. A recently available study [17] examined TCR and B cell receptor (BCR) repertoires in sorted cell subsets of tumor, faraway non-tumor tissues (NT), and peripheral compartments (bloodstream/draining lymph node) from 47 non-small cell lung cancers (NSCLC) sufferers and identified distinctive adaptive immune replies in NSCLC. The current presence of tertiary lymphoid buildings (TLSs) in the microenvironment of lung cancers also improved the T cell clonal enlargement in tumors. Nevertheless, the relationship between your variety of TCR clones as well as the clinical top features of the lung cancers patients is not further explored. Right here, we likened the regularity of T cell clones as well as the AZD6738 ic50 clonal variety of TCR repertoires in lung cancers tissue as well as the matched up normal lung tissue to elucidate the association between TCR variety as well as the prognosis of lung cancers patients. Outcomes Global profile from the TCR repertoire sequencing data To measure the TCR repertoire in the tumor tissue and normal tissue of sufferers with lung cancers, we attained RNA from 30 matched specimens isolated in the 15 sufferers and performed TCR sequencing by amplifying the TCR CDR3 area, a technique that people acquired used [15], [18]. Detailed information about the TCR repertoire data is included in Table S1. We obtained a total of 125,075,908 productive TCR reads (sequence of the read is in frame and does not have a premature quit codon), with an average of 4,169,197 reads per sample. In tumor tissues, 3,015,213C5,733,528 productive reads were obtained, and AZD6738 ic50 331,272C727,815 unique clones were recognized, whereas 2,639,987C5,797,795 productive reads and 274,202C615,647 unique clones were obtained in the normal lung tissues. The distribution of the productive reads in tumor tissues and normal lung tissues was comparable ( em P /em ?=?0.978, Figure 1A), but.
Posted on June 29, 2020 by bioentryplusPosted in GPR35Tagged AZD6738 ic50, Mouse monoclonal to STAT5B
Data Availability StatementAll IMC data are available at https://osf. issues in
Data Availability StatementAll IMC data are available at https://osf. issues in image digesting connected with tellurium IMC data. Right here, we address a few of these presssing problems by demonstrating removing xenon history sign, combining stations to boost signal-to-noise percentage, and determining isotope transmission effectiveness biases. These advancements add precision to the initial temporal quality afforded by tellurium Salinomycin enzyme inhibitor IMC probes. Intro The growing technology of imaging mass cytometry (IMC) offers delivered understanding into many areas of biology like the heterogeneity of breasts cancer tumours as Salinomycin enzyme inhibitor well as the cells distribution of cisplatin. [1, 2] Cells areas are stained with an increase of than 40 different antibodies, each which can be conjugated to a polymer that chelates a definite elemental isotope, through the lanthanide series typically. The section can be ablated pixelwise with a rastering after that, pulsed ultraviolet laser beam. The ablated materials from each pixel goes by into an inductively-coupled plasma mass spectrometer and each isotope, which corresponds Salinomycin enzyme inhibitor to Salinomycin enzyme inhibitor a particular antibody, can be quantified. A multi-channel picture is thereby made up of a lot more stations accessible than traditional immunofluorescent or immunohistochemical optical imaging. This technique continues to be limited by the imaging of static natural markers (i.e. protein), DNA, or particular little molecule probes against which custom made antibodies have already been elevated (e.g. EF5). [1, 3] With tellurium as an IMC-visible component, we have created tellurophenes as biologically-compatible mass tags whose imaging needs no antibody staining. [4] Probes for particular biological processes can be synthesized by linking tellurophenes, which are aromatic, IL1R2 antibody stable, and nontoxic, to activity-based functional groups that covalently bind cells of a certain phenotype. In this way, IMC can be used to visualize processes or microenvironments including protein synthesis and cellular hypoxia. [5, 6] Imaging of these compounds is not dependent on antibody-epitope binding and as such represents direct visualization of the probe itself. Tellurium exists naturally as a mixture of eight stable isotopes, of which six are commercially available in an isotopically-enriched form. If a robust probe is developed and synthesized in isotopically-enriched variants, its target biochemical process may be investigated with spatial and temporal resolution with IMC. For example, changes in hypoxia over time were quantified by dosing one isotope of a tellurophene conjugated to a 2-nitroimidazole group, followed by waiting or an intervention, followed by a dose of the same molecule made up of the second isotope. [6] The single mass unit resolution of IMC then allows quantification of the difference in labelling of the probes. We term this approach sequential labelling of isotopologous probes (SLIP). SLIP experiments with tellurium add temporal resolution to the IMC toolbox, which is crucial in understanding the deep biological profile imaged by IMC. Despite the specific benefits of tellurium probes, the element brings unique data processing challenges. Contamination with overlapping isotopes of xenon can cause significant background signal, and differences in detection efficiency across isotopes may reduce the accuracy of SLIP experiments. In addition, when natural abundance tellurium probes are used, it is possible to improve the signal-to-noise ratio by combing signals across multiple mass channels. While software for analyzing IMC data exist, [7, 8] they do not deal explicitly with tellurium as an analyte and so do not treat these challenges. Given the specific great things about tellurophene probes, we searched for to create Salinomycin enzyme inhibitor data digesting strategies that could improve the precision of research within this field and invite SLIP experiments to become included as solid strategies in the IMC community. Components and methods Organic abundance intestine picture We utilized IMC data from our prior publication describing a tellurium-containing probe for proteins synthesis, where in fact the test is certainly described at length. [5] Quickly, mice had been injected with TePhe (60 mg kg?1,.
Posted on June 27, 2020 by bioentryplusPosted in GPR35Tagged IL1R2 antibody, Salinomycin enzyme inhibitor
Matrix Gla Protein (MGP), a little Gla supplement K-dependent protein, may
Matrix Gla Protein (MGP), a little Gla supplement K-dependent protein, may be the most powerful normal occurring inhibitor of calcification in our body. factors all-trigger/CV mortality and nonfatal CV event. KaplanCMeier curves demonstrated that RepSox inhibitor circulating dpucMGP 646 pM (median worth) was connected with all-trigger, CV mortality, and CV events (= 0.011, = 0.008, and = 0.019 respectively, log-rank test). After adjustment for many established risk elements for mortality and CVD (age group, sex, BMI, background of CVD, smoking cigarettes, duration of hypertension and T2DM, dyslipidemia, glycated hemoglobin), multivariate Cox evaluation demonstrated that high serum dpucMGP 646pM was connected with higher all-trigger mortality (HR 2.97, 95% CI = 1.27C6.95, = 0.012), CV mortality (HR 5.49, 95% CI = 1.85C16.33, = 0.002), and nonfatal CV occasions (HR 2.07, 95% CI = 1.00C4.20, = 0.047) in comparison to sufferers in the reduced dpucMGP group [100]. Likewise, in a cohort of 518 kidney transplant recipients with CKD, elevated plasma degrees of dpucMGP had been connected with a three-fold higher general mortality risk and a far more than two-fold risk for incidence of transplant failing. After adjustment for many confounders, the association between circulating dpucMGP and higher mortality risk persisted and with transplant failing was lost [101]. Both dephosphorylated types of MGP (dpucMGP and dpcMGP) had been assessed in a cohort of 188 steady, maintenance HD sufferers, followed for three years. Both KaplanCMeier curves and multivariate Cox analyses altered for age demonstrated that low dpcMGP 6139 pmol/L was connected with general mortality (HR 2.31, 95% CI = 1.2C4.4, = 0.01) and CV mortality (HR 2.94, 95% CI = 1.4C6.3, = 0.006). Although KaplanCMeier curves demonstrated that dpucMGP was marginally not really connected with overall (= 0.08, log-rank check) and CV mortality (= 0.09, log-rank test), univariate Cox analysis showed that low serum degrees of dpucMGP 442 pmol/L were connected with overall mortality (HR 1.71, 95% CI = 0.92C3.17, = 0.09), and CV mortality (HR 1.83, 95% RepSox inhibitor CI = 0.90C3.70, = 0.09) [68]. 5.4. Patients with Great CVD Risk and Cardiovascular Failure Ueland et al. showed that only circulating dpucMGP (and not dpcMGP) was strongly and independently associated with deterioration of heart failure and overall mortality in a cohort of 147 patients with symptomatic, severe, calcific aortic stenosis [89]. In agreement with these results, a recent study reported that high plasma dpucMGP levels were associated with deterioration of heart function (diastolic left ventricular dysfunction) in both epidemiological and histological findings in the general population, and also patients with heart failure [59]. In 179 patients with chronic heart failure, high serum dpucMGP (and not dpcMGP) levels were strongly and independently associated with death from deterioration of heart failure [64]. The multi-center ASTRONOMER trial (aortic stenosis observation: measuring effects of rosuvastatin), included 215 patients aged 18C82 years with moderate or moderate aortic stenosis, and reported that high serum dpMGP levels were independent predictors of disease progression, especially in more youthful subjects [102]. Mayer et al. conducted a prospective cohort RepSox inhibitor trial to investigate the possible predictive value of dpucMGP for mortality in subjects with stable vascular disease. For a median of 5.6 years, 799 patients with history of myocardial infraction (MI), Rabbit Polyclonal to GFR alpha-1 stroke, RepSox inhibitor or CAD were followed. In multivariate Cox regression analysis, it was shown that patients in the highest dpucMGP tertile (dpucMGP over 977 pmol/L) experienced a significantly increased risk for CV and overall mortality (HR 1.88, 95% CI = 1.22C2.90 and HR 1.89, 95% CI = 1.32C2.72, respectively). Corresponding HR for serum dpcMGP were 1.76, (95% CI = 1.18C2.61) and 1.79 (95% CI = 1.12C2.57). Low ucMGP plasma levels 2825 nmol/L were associated with high risk for overall mortality (HR 1.43, 95% CI =1.01C2.03) and CV mortality (HR 1.33, 95% CI =1.01C2.01). The authors concluded that, since the data regarding the association.
Posted on December 4, 2019 by bioentryplusPosted in GPR35Tagged Rabbit Polyclonal to GFR alpha-1, RepSox inhibitor
Today's study seeks to identify the nutritional risk factors involved in
Today's study seeks to identify the nutritional risk factors involved in the development of neuropathies induced by chemotherapeutic treatments. the group without CIPN were estimated to be 38.2 (24.95, 47.63) nmol/L, whereas in the group with CIPN it was determined to be 25.6 (19.7, 32.55) nmol/L, = 0.008. The level of total saturated fatty acids in the group without CIPN was of 32.613 Area % (31.322; 36.262), whereas in the group with CIPN it was of 34.209 Area % (32.86; 39.386), = 0.01. The obtained results suggest a diet lower in saturated fatty acid content during chemotherapy. The most significant finding was that supplementation of vitamin D before chemotherapy could be an efficient neuroprotective in CIPN prophylaxis, as significantly lower levels 25OH derivative of vitamin D were observed in the CIPN group throughout the study period. 0.05. Receiver operating characteristic (ROC) was determined using the software Analyse-it for MS Excel (Analyse-it Software, Ltd., Leeds, UK). The clinical evaluation of the patients was determined using the Michigan questionnaire, a Michigan neuropathy screening instrument, patient version (A) and physical assessment (B); MNSI, University of Michigan, 2000 [17]. The scores were calculated as ratio/total score (interval from 0 to 1 1) and are presented in Table 3. The evaluation of the patients was performed (a) before chemotherapy (Evaluation 0), (b) during chemotherapy (Week 4; Evaluation 1), and (c) at the end of chemotherapy (Week 12, Evaluation 2). Table 3 Neuropathy Cisplatin pontent inhibitor evaluation by means of a Cisplatin pontent inhibitor Michigan questionnaire. ValueValueValue= 0.0023), cutoff value 34 nmol/Lsensitivity 80%, specificity 65%. Open in a separate window Figure 2 ROC curveselected fatty acidtotal saturated fatty acids (area 0.68, = 0.0036), omega 7 classpalmitoopleic acidC16:1 (area 0.65, = 0.01) and sum of omega 3 fatty acid (area 0.57, = 0.152). Prior to chemotherapeutic treatment, we observed statistically significant differences between the CIPN 1 and CIPN 0 groups concerning vitamin Mouse monoclonal to EPCAM D deficiency, unsaturated fatty acids (C12:0, C14:0, C16:1), and total saturated fatty acids (tSFA). The polyneuropathy group (CIPN 1) presented a significant difference between the concentration of fatty acids before, and/or during, and/or the end of therapy, i.e., C12:0, C14:0, C16:0, C 18:0, C18:2 n6, C20:3 n6, C20:4 n6, C20:5 n3, tSFA, n6, n3, AA/EPA (ratio arachidonic acid and eicosapentaenoic acid), and total polyunsaturated fatty acids (tPUFA). Additionally, vitamin D concentration was found in a significantly lower concentration during treatment. The group without polyneuropathy (CIPN 0) also showed a significant difference between the concentration of fatty acids before, during, and at the end of chemotherapeutic treatment, i.e., C14:0, C16:0, C18:3 n6, C20:3 n6, C20:4 n6, C22:6 n3, tSFA, n6, n3, and tPUFA. Likewise, vitamin D concentration decreased significantly during the treatment. However, with the exception of n3, the drop in the evaluated parameters was lower in the control group than in the CIPN 1 group. The analysis on polyneuropathy occurrence in cancer patients after chemotherapy, evaluated at Weeks 1, 4, and 14 post-treatment, reflects the worsening of symptoms induced by chemotherapeutic drugs. 4. Discussion We performed a prospective evaluation of risk factors involved in chemotherapy-induced polyneuropathy, although a complete description of chemotherapy-induced neuropathy risk and protective factors has yet to be described. Our potential trial Cisplatin pontent inhibitor resolved the clinical top features of chemotherapy-induced neuropathy and the partnership between the intensity of the Cisplatin pontent inhibitor pathology and the depletion of potential Cisplatin pontent inhibitor safety elements. The incidence of polyneuropathy can be partially reliant on the rate of recurrence of provided taxane-centered or oxaliplatine-based medicine. Recapitulating previous research, cisplatine and taxol induced the sign starting point of a genuine sensory neuropathy, concerning compromised sensitivity to discomfort, contact, and vibrations generally in most of our individuals [1,4,5,6,12,14,18,19], hardly ever reporting an agonizing sensation. Our medical results were.
Posted on November 28, 2019 by bioentryplusPosted in GPR35Tagged Cisplatin pontent inhibitor, Mouse monoclonal to EPCAM
Supplementary MaterialsGIGA-D-18-00445_Initial_Submission. good practice. Moreover, research is usually often characterized by
Supplementary MaterialsGIGA-D-18-00445_Initial_Submission. good practice. Moreover, research is usually often characterized by a lack of established methods. Despite the crucial importance of researcher conduct, research and conclusive data around the determinants of researcher behavior are widely missing. Conclusion Meta-research that establishes an understanding of the factors that determine researcher Abiraterone biological activity behavior is usually urgently needed. This knowledge can then be used to implement and iteratively improve steps that incentivize experts to apply the highest standards, leading to high-quality data. research, nearly all respondents (52% of just one 1,576 respondents, 86% of 480 respondents) decided a reproducibility turmoil is available [24, 25]. Open up in another window Amount 1: Variety of content that are discovered by the keyphrases replication turmoil (crimson) or reproducibility turmoil (blue) each year from 1965 to 2017 in PubMed (13], data reached on 12 January 2018). Outcomes Range of turmoil continues to be unclear Regardless of the high presence from the presssing concern, systematic analysis and subsequently conclusive evidence over the scale of the potential reproducibility problems are lacking. Inside a survey among faculty and trainees in the MD Anderson Malignancy Center, about 50% of the participants reported that they had failed to reproduce published data at least once [26]. Similarly, inside a survey 70% of the 1,576 respondents stated that they had been unable to reproduce data at least once [24]. However, systematic data that would enable the reliable quantification of the issue are lacking. In the Reproducibility Project: Malignancy Biology by the Center for Open Technology [27] and Technology Exchange [28], findings from 29 high-profile medical publications will become individually replicated [29C31]. To date, the results of 11 replication studies have been Abiraterone biological activity reported. Important parts of the original paper could be reproduced in four studies [32C35]. The results from two replication studies could not become interpreted [36, 37], and two studies failed to replicate the original findings [38, 39]. In three further reports, some parts of the original studies were reproduced while others were not [40C42] (Table ?(Table11). Table 1: Replication studies performed as part of the Replication Project: Malignancy Biology [30], offered according to the end result as interpreted in the Editors Summary infection is common in human being colorectal carcinoma [38] Open in a separate windows 1Number in the research list. Psychological studies also seem to vary with regard to replication success. Very low levels of reproducibility have been reported in some cases [43, 44]. A report by the Open Abiraterone biological activity up Abiraterone biological activity Science Cooperation reported the effective replication of 39 of 100 emotional research [9]. However, various other research replicated most the analyzed results [45] or verified previous results [46, 47]. A dataset supplied a qualitative set of 54 replication tries of implicit Theory of Brain paradigms predicated on a study [48]. Twenty-six research (48%) were effectively replicated, 15 research (28%) were partly replicated, and 13 research (24%) weren't effectively replicated [48]. In the scientific analysis field, an evaluation of follow-up magazines of 49 primary clinical clinical tests that were released between 1990 and 2003 and acquired each acquired a lot more than 1000 citations uncovered that 7 (16%) weren't confirmed by following research, 7 (16%) acquired reported stronger results than those within subsequent research, 20 (44%) had been effectively replicated, as well as for 11 (24%) follow-up data weren't available [1]. Another research compared the full total outcomes from a restricted variety of preliminary scientific research and particular follow-up research. It figured significantly less than 50% from the looked into research reported reproducible results [49]. However, it is not obvious how representative the data are. Notably, reproducibility data have also been reported in content articles other than unique study content articles. For example, experts from drug companies reported that only 6 PGC1A out of 53 studies (11%) [5] or 16 out of 67 studies (24%) Abiraterone biological activity [3] had been successfully reproduced. However, these data had been published being a Comment [5] and a Correspondence [3] without display of comprehensive data. Hence, the precise nature from the investigations as well as the requirements for reproducibility stay elusive. Taken jointly, a couple of anecdotal reviews of data irreproducibility. Nevertheless, the actual scale from the presssing issue remains unclear because of too little systematic data. Most replication tries.
Posted on September 9, 2019 by bioentryplusPosted in GPR35Tagged Abiraterone biological activity, PGC1A
Schistosomiasis is a debilitating disease affecting approximately 600 mil people in
Schistosomiasis is a debilitating disease affecting approximately 600 mil people in 74 developing countries, with 800 million, mostly children at risk. contrary to the surface membrane molecules, are entirely accessible to the sponsor immune system effector elements. We have proposed that the use of these molecules, in conjunction with Th2 cytokines-inducing adjuvants for recruiting and activating eosinophils and basophils, will likely lead to development and implementation of a sterilizing vaccine inside a near long term. trematodes that live in the bloodstream of humans and animals. Three varieties (and and schistosomula are present only in the blood-free, lymph-free epidermis. Majority of schistosomula are found in CX3CL1 the dermis only after 48?h, and they appear to reach the dermal vessels around 72?h after illness [8,9]. Once in the blood capillaries, the schistosomula are carried passively from the blood flow till reaching the right heart and then the lungs. Depending on the varieties, schistosomula stay inside the pulmonary capillaries from 3 to 16?days, where they change into much longer and slender organisms, such a shape that enables them to traverse the thin pulmonary capillaries to the left heart and SP600125 irreversible inhibition the systemic SP600125 irreversible inhibition blood circulation [10]. Following this period, the larvae make their way to the liver via the splanchnic vasculature. Upon reaching the liver, schistosomula start feeding and growing by active cell division. Once they reach maturity the worms start pairing, between 28 and 35?times post-infection. The matched adults migrate from the liver organ, using the male having the feminine, to where they'll finally have a home in the mesenteric blood vessels ([analyzed in 19]. Schistosomicides Antimonial substances, employed for treat SP600125 irreversible inhibition of leishmaniasis generally, have already been the cornerstone of schistosome chemotherapy for approximately 50?years. Their setting of action is normally thought to be solid inhibition from the schistosome phosphofructokinase (the enzyme catalyzing the transformation of fructose-6-phosphate to fructose-1,6-diphosphate) at concentrations 65C80 situations less than those effective against the individual enzyme [20]. This wide difference signifies that inhibition of web host phosphofructokinase can't be the just trigger for the antimonial medications extreme toxicity and serious side effects, that have rendered them obsolete today. The organophosphorus insecticide 2,2,2-trichloro-1-hydroxyethyl dimethyl phosphonate was somewhat modified to provide rise to metrifonate (towards the liver organ also to the lungs via the vena cava. Upon medication concentration decrease, can handle regaining their primary area in the mesenteric blood vessels, whereas remain captured in the lungs [23]. This may describe that metrifonate mediates eliminating of however, not to 1C3?M PZQ undergo nearly instant spastic paralysis. In parallel, vacuolization of elements of the top and tegument blebbing take place, especially in man worms (Desk 1). All worms thereafter die. These reproducible results SP600125 irreversible inhibition show that adult schistosomes bind PZQ, and that PZQ per se is definitely schistosomicidal [31]. and in experimentally infected animals [71]. A single oral injection of 400?mg/kg artemether to mice infected with approximately 80 cercariae of 21 (pre-patent) or 49 (patent period) days earlier led to 71C81% reduction in total worm burden [72C75]. Mefloquine, another anti-malarial drug, was also found to have significant anti-schistosome activity as well, as a single dose (200 or 400?mg/kg), administered orally to mice infected with adult and against and and and redox protein thioredoxin-glutathione reductase [81,82]. Trioxaquines, cross drugs comprising a 1,2,4-trioxane and a 4-aminoquinoline, initially developed against malaria, show a dual mode of action: alkylation of heme with the trioxane entity, and stacking with heme due to the aminoquinoline moiety, leading to inhibition of hemozoin formation activity and schistosomicidal effects [84]. Of great interest is the class of compounds focusing on schistosome histone modifying enzymes, namely histone acetyltransferases and histone deacetylases, and leading to parasite apoptosis and death in ethnicities [85]. Plant-derived schistosomicidal compounds A different approach to therapy of schistosomiasis relied on vegetation known for medicinal effects. Extracts and oils.
Posted on September 7, 2019 by bioentryplusPosted in GPR35Tagged CX3CL1, SP600125 irreversible inhibition
NMDA receptor (NMDAR) activation requires concurrent membrane depolarization, and glutamatergic synapses
NMDA receptor (NMDAR) activation requires concurrent membrane depolarization, and glutamatergic synapses lacking AMPA receptors (AMPARs) are often considered silent in the absence of another source of membrane depolarization. layers?= 742)37.8 5.356.0 4.06.4 1.3(= 412) Open in a separate windows Data are expressed as percentages and represent the mean and standard error for those asymmetric synapses falling into each category, derived from exam in three animals per age group (214, 253, and 275 synapses from your three adult animals and 170, 119, and 123 synapses from your three PD 7 animals, respectively). The AMPAR labeling groups are as illustrated in Number 5points to the curvature of the PSD. The axon terminal, identifiable by synaptic vesicles ((are characteristic of immature synapses. show terminals with large cytoplasmic volumes devoid of vesicles. This is a recurrent feature of PD 7 neuropil. denote the ER lumen. Level bar (demonstrated in for in particular) but was not as common as postsynaptic labeling. The overall incidence of = 420)23.5 4.521.6 4.0 (= 270) Open in a separate window Notice the prevalence of axonCspine junctions among both and of the spine apparatus (in in in (with and with for 0.05; two-tailed test) and likewise within Mitoxantrone manufacturer each cortical coating examined (superficial, middle, and deep, with all categories of AMPAR immunoreactivity combined; data not demonstrated). To assess the regularity of results between experimental animals, pairwise tests were performed among animals of the same age group and within the same cortical coating. Of 18 possible comparisons, 17 yielded no significant difference between animals ( 0.5), whereas one pair (in PD 7, deep layers) was significantly different (= 0.003). We did not detect significant layer-dependent variations in the denseness of for an electron micrograph illustrating these groups. represent PD 7, and represent adult synapses. Synapses across all cortical layers and from three animals of each group are combined in each storyline. 2) are 0.088 for AMPAR++ adult (= 42), 0.105 for AMPAR++ PD 7 (= 15), 0.089 for AMPAR+ adult (= 209), 0.196 for AMPAR+ PD 7 (= 129), 0.075 for AMPAR+/? adult (= 88), and 0.070 for AMPAR+/? PD 7 (= 67). We examined whether the variance in denseness of Mitoxantrone manufacturer in each histogram; compare (experimental) with (Poisson)], and this population is larger in the PD 7 group than in the adult group. (2) The PD 7 group consists of a statistically unique sub-population of 21 synaptic profiles with a relatively high denseness of of of 0.05; KolmogorovCSmirnov test). Experimental data from PD 7 for bin ranges 5C100 C1qtnf5 (i.e., including synapses with 50 platinum particles per micrometer) differed significantly from a Poisson distribution match to that Mitoxantrone manufacturer range of bins ( 0.05; KolmogorovCSmirnov test; graph not demonstrated). The percentage of truly bad synapses (measured value minus Poisson value, of = 420 synapses for adult; = 270 synapses for PD 7. The adult sample included one profile with 179 particles per micrometer that was excluded from your statistical analysis. The data for PD 7 are offered like a scatter storyline in Number 9, subdivided according to the amount of AMPAR labeling at each synapse. Mitoxantrone manufacturer The story implies that the band of information with 50 or even more gold contaminants per micrometer consisted mainly of these with relatively brief active areas (250 nm or much less) and without extreme AMPAR labeling. Eleven of the synapses belonged to the superficial levels, four belonged to the center levels, and six belonged to the deep levels. Fourteen from the synapses had been judged to become axospinous, whereas one (in level VI) was axon-shaft, and six cannot be classified as you or the various other. Of the densely above the match those to the proper from the 50 particle per micrometer bin (inclusive) in the PD 7 histogram (Fig. 8). Take note the relative lack of larger synaptic profiles and AMPAR-positive synapses within this group intensely. The info set may be the same one employed for PD 7 in Amount 7. Debate Prevalence of postsynaptic em /em 7nAChR in both adult and neonatal somatosensory cortex suggests a popular function in excitatory transmitting A big body of function documents the impact of cholinergic activity on.
Posted on September 1, 2019 by bioentryplusPosted in GPR35Tagged C1qtnf5, Mitoxantrone manufacturer
Nanotechnology has large applications in many fields, especially in the biological
Nanotechnology has large applications in many fields, especially in the biological sciences and medicine. nanomaterials in human being medicine and in the environment while others are in favor. The important point here is that because there are many nanomaterials with many different uses, it is difficult to test all of them and estimate their effects on human being health. Consequently, some scientists believe that their side effects are suitable.1,2 Considering all factors, screening the effects of nanomaterials on mammals and the environment is necessary. Only with more study, and using medical evidence, microscopy tools, and modern analysis methods, Decitabine distributor can we discover the advantages or disadvantages of their applications. New features of nano-sized materials can be found, including electrical conductivity, reactivity, stability, colorability, and toxicity.2 Carbon in the form of graphite is soft and malleable, although at a nano-sized level, it becomes a nanocarbon tube, which is tougher than steel. One gram of catalyst with a diameter of 10 nm is about 100 times more reactive than a similar particle with a diameter of 1 1 m. However, toxicity occurs with nano- and micron-sized particles. The important fact about nanoparticles is their remarkable reactivity, a characteristic that may result in toxicity effects.1,2 In this review article, nanobiomaterials used in the field of medical sciences are discussed, along with their toxicity effects. Nanotoxicology Nanotoxicology is a branch of bionanoscience, which deals with the study and application of the toxicity of nanomaterials. Nanomaterials, even when made of inert elements such as gold, become highly active at nanometer dimensions. Nanotoxicological studies are used to determine whether and to what extent these properties may pose a threat to the environment and to human health.3 Nanoparticles play a remarkable role in toxicity, which is important for toxicologists, especially in respiratory diseases. Their size is an important factor in the occurrence of disease. Some studies on the different sizes of carbon and titanium oxide showed that reduction in nanoparticle size increases its toxicity in the lungs. Also notable is that combining some metals with each other causes complex toxicity, which does not occur with single metals. In 1975, a study showed the effect of oxidative stress caused by asbestos as the main factor in asbestosis and also in disturbing cell structure. In 1998, Zhang presented his findings on the effects of nanoparticles on respiratory toxicity and inflammation.4 Some of the particle features such as size, surface chemistry, and Decitabine distributor oxidative stress functions play important roles in nanotoxicity. Other features such as crystallinity, coating, and the longevity of Rabbit polyclonal to AADACL3 particles have also been studied as important parameters.5 By gaining control over dangerous particles, we can increase the use of nanoparticles by reducing Decitabine distributor their harmful effects, and thus allowing them Decitabine distributor to be used in the curing of diseases.5C9 Important factors Size For particle toxicity, two factors are important: size and chemical compounds. A reduction in the size of nano-sized particles results in an increase in particle surface area. Therefore more chemical molecules may attach to this surface, which would enhance its result and reactivity in an increase in its toxic effects.8,9 Many reports for the absorption of nanoparticles from these effects have already been analyzed from the mucus. After absorption, nanoparticles reach the bloodstream and pass on through the cells. In one research, 33% of 50 nm,.
Posted on August 26, 2019 by bioentryplusPosted in GPR35Tagged Decitabine distributor, Rabbit polyclonal to AADACL3
The stable incidence of new leprosy cases suggests that transmission of
The stable incidence of new leprosy cases suggests that transmission of infection continues despite worldwide implementation of MDT. by microscopic exam is required for leprosy classification, choice in choosing and monitoring chemotherapy regimens, and analysis of relapse. However, detection and quantification using standard microscopy yields data of limited specificity and level of sensitivity. Thus, in order to match current clinical methods, especially for PB patients, and to allow informed decision making on who needs treatment at a preclinical stage, several groups are investigating design of improved diagnostic tools. These tools will reduce transmission, prevent practical disabilities and stigmatizing deformities, and help leprosy eradication, especially in individuals at risk for developing leprosy such as close contacts of leprosy individuals. Assays have been developed that detect antigens can Rabbit Polyclonal to FOXD3 cross-react in the T-cell level with antigens present in other mycobacteria, like or BCG actually if the homology is definitely relatively low as is the case for ESAT-6 and CFP-10 [7, 8]. Using comparative genomics, we previously recognized candidate proteins highly restricted to which showed promising features with respect to software in leprosy diagnostics [9, 10]. For specific detection of illness, commercially available IFN-release assays (IGRAs) like QuantiFERON-TB Platinum have been developed [11]: these checks are based on cellular immune reactions induced by a cocktail of peptides derived from ESAT-6 (Rv3875), CFP-10 (Rv3874), and TB7.7 (Rv2654) that are selectively expressed by and deleted from all (nonvirulent) BCG strains and most other NTMs [11]. This has influenced research into the feasibility Duloxetine manufacturer of developing related peptide-based assays for the recognition of asymptomatic leprosy: motivating results have been generated indicating that some synthetic peptides induce specific reactions in individuals exposed to and could potentially be developed into a rapid test for the detection of illness [10, 12, 13]. In contrast to TB, however, ESAT-6- or CFP-10-derived peptides will not be useful due to the cross-reactive T-cell reactions they induce in TB individuals [7, 8]. Since T-cell reactivity to peptides are HLA-restricted [14C16], the use of a pool composed of several different peptides, in analogy to the pool of peptides applied in the QuantiFERON-TB Platinum tests, will increase awareness [17, 18], while staying away from T-cell cross-reactivity. To be able to improve awareness of a particular diagnostic peptide mix, we have within this research extended the amount of peptides with potential to tell apart contact with from BCG vaccination and contact with various other mycobacteria in another diagnostic device. The proteins ML1601c once was discovered by us Duloxetine manufacturer as extremely immunogenic in creation in Brazilian leprosy sufferers and handles in response to overlapping ML1601c peptides within the entire proteins. 2. Methods and Materials 2.1. Artificial Peptides ML1601c overlapping peptides (Desk 1: two 19-mers with 9 amino acidity overlap; eight 20-mers with 10 amino acidity overlap; one 21-mer with 10 proteins Duloxetine manufacturer overlap) were bought from Peptide 2.0 Inc. (Chantilly, VA, USA). Purity and Homogeneity were confirmed by analytical HPLC and by mass spectrometry. Purity of most peptides was 80%. All pollutants contain shorter versions from the peptides due to 100% coupling performance in each circular of synthesis. Aliquots of similar batches from the artificial peptides were examined in Brazil, Ethiopia, and HOLLAND. Desk 1 ML1601c artificial peptides. and cloned using the Gateway technology system (Invitrogen, Carlsbad, CA, USA) with pDEST17 appearance vector filled with an N-terminal histidine label (Invitrogen) [19]. Sequencing was performed on chosen clones to verify identity of most cloned DNA fragments. Recombinant protein had been overexpressed in BL21 (DE3) and purified as defined to eliminate any traces of endotoxin. Each purified recombinant proteins was examined by 12% SDS-PAGE accompanied by Coomassie Outstanding Blue staining and traditional western blotting with an anti-His antibody (Invitrogen) to verify size and purity. Endotoxin items had been below 50?IU per mg recombinant proteins as tested utilizing a Limulus Amebocyte Lysate (LAL) assay (Cambrex, East Rutherford, NJ, USA). Recombinant ML1601c proteins was tested to exclude protein nonspecific T-cell.
Posted on August 24, 2019 by bioentryplusPosted in GPR35Tagged Duloxetine manufacturer, Rabbit Polyclonal to FOXD3


Pot roast is the sweat suit of the culinary world: comfortable, doesn't really take much thought to throw it on, and at times, just sort of sad. But this recipe for pot roast is much sexier. It's less sweatpants and far more hot pants. And it's really not much more difficult than your traditional dump-everything-in-a-pot and-cook-all-day classic. A couple of fancy ingredients makeover the grayish stew we all remember into something more special and worthy of a nice bottle of red wine.
First things first, you need to revive the dried mushrooms. Bring the cup of chicken stock to boil on the stove and add the mushrooms. Take off the heat and cover for 15-20 minutes until they reconstitute.
While that's happening, grab your hunk of meat and season with salt and pepper.
Heat a tablespoon of olive oil in a large dutch oven over medium high heat and brown the chuck roast on all sides. While the meat is browning, chop your veg.
Pull the roast out of the dutch oven and set on a plate to hang out while you get its tasty bath ready.
Keep the dutch oven at medium to medium-high heat and add the onions and celery to cook until they begin to brown – about 6-7 minutes. While they're browning, grab your mushrooms in stock and fish them out with a slotted spoon, taking care to save the liquid. Roughly chop your mushrooms and garlic.
Add the garlic and porcinis to the browned onions and celery and cook for another minute.
Now add the tomatoes and chicken/porcini broth to the pan. If you only have diced or crushed tomatoes like I did, don't worry about it. Those will work just fine. After cooking the tomatoes for about 5 minutes, add the cup of red wine and bring the mixture to a boil.
Remember the beef? Take that little guy and nestle him in that tasty liquid and pop the lid on the whole thing.
Put it in your preheated oven and cook for an hour and a half. Pull the dutch oven out and flip the meat over and cook for another hour and a half or until it begins to get nice and tender. I think we cooked ours for closer to three and a half hours.
Once the beast has spent its allocated time in the oven, pull the roast out and set aside, tented with foil, while you finish the sauce. Bring the mixture to a boil and reduce for 5-10 minutes until it's the consistency you like. Slice up the pot roast and serve over mashed potatoes with a healthy ladleful of sauce.
Now, ain't that pretty? Take off that sweat suit and throw on some heels.


JACKSON, LA (WAFB) - East Feliciana Parish Sheriff's Office authorities announced Wednesday they arrested the son of Baton Rouge serial killer, Derrick Todd Lee, last week in connection with the shooting death of 16-year-old, Valentae Brooks.
Dedrick Lee, 19, is charged with negligent homicide after he reportedly confessed to accidentally shooting Brooks on November 13. Sheriff Jeff Travis says the two teens were at Lee's house in the 2800 block of Charles Drive in Jackson when the shooting occurred.
He added investigators are still working to determine if all the evidence matches Lee's confession.


AutoFurniture is a set of really clever dynamic colored furniture blocks. Dynamic parameters allow furnishing of all kinds of residential, hotel and office buildings with just few blocks. You get impressive drawings without digging into huge libraries or redefining blocks. Editing drawing is quick and easy. Color hatches are in a separate layer and turning it off you can use the blocks in technical drawings too. The blocks are arranged in a tool palette in order to be easily accessed.


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Greatest Episodes #53: Run For Your Life: "Time and a Half on Christmas Eve" (December 19, 1966)
It's hard to find a lousy episode of The Dick Van Dyke Show, but a good place to start would be the third season's Christmas show, "The Alan Brady Show Presents," in which the usual precision-tooled wit takes a holiday break and the lets the cast flounder in some self-indulgent variety-show routines. If ever a series earned the right to phone one in during Christmas week, it's Carl Reiner's masterpiece. But "The Alan Brady Show Presents" is part of an unhappy tradition, in which shows that should know better put their usual formulas on pause and pander to the season with religiosity and cheap sentimentality. That's how you ended up with Bewitched's pagan Samantha and skeptic Darrin not only celebrating Christmas, but spending it in blackface. Bah, humbug!
But every rule has an exception. There's one nearly forgotten Christmas-themed entry that may actually be the best episode of the series it was part of. Called "Time and a Half on Christmas Eve," it first aired in December 1966, during the second season of Run For Your Life.
A lower-stakes knock-off of The Fugitive, Roy Huggins's Run For Your Life starred Ben Gazzara as Paul Bryan, a lawyer who goes on a well-heeled walkabout after being diagnosed with a terminal illness. "Time and a Half" strands him in a small town where he knows no one after some Christmas Eve engine trouble forces his flight to divert. Stepping away from the other passengers to make a phone call, Bryan returns to find the terminal unexpectedly empty; everyone else has already caught a ride to a motel. That moment of disorientation hints at "Time and a Half"'s true subject: it's about being alone, literally or otherwise, during the holidays. Bryan catches a ride with Harry Martin (Ernest Borgnine), a cab driver so hearty verging on overbearing that he hauls over to the side of the road and shows the Salvation Army Santa how to ring his bell harder. (It's a perfect role for Ernest Borgnine – another variation on Marty Piletti). The pair end up in Harry's favorite bar, a run-down dump that's expectedly empty except for Sam (Charles McGraw) and Jeannie (Melanie Alexander), the bartender and waitress who pass for his best friends. Although they're fond of Harry, they're not ready to party all night with him; Sam has a family and Jeannie a boyfriend, something the cabbie didn't realize, or pretended not to. As they close up the bar, Jeannie gives him a look and says something about "fifty miles north."
Harry is a proud loner who praises himself for having avoided the "traps" of ordinary life that burden other people. Fifty miles north turns out to be where the wife and child he abandoned years earlier now live. Urged on by Paul, who senses Harry's deep-seated unhappiness, they pick up some last-minute gifts and undertake a road trip to find out what happened to the lost family. That way lies heartbreak. "Time and a Half" ends on an upbeat note, albeit a brief one, following a troubling climax which suggests, through a sharp metaphor, that suicide may lie in Harry's future. A. Martin Zweiback's teleplay (from a story by Daniel L. Aubry) is full of wry details and smart dialogue. Bryan learns of the airplane's distress before the captain announces it because he happens to be sitting next to an airline engineer who hears the engine struggling: exposition dissolved in humor. The walls of the podunk airport are adorned with a cheesecake calendar and a "Worms For Sale" sign. "'Bob,' he asked disappointedly?" is Paul's response when the stewardess he's trying to pick up tells him she's engaged to the pilot. Although Paul Bryan was a ladies' man through-and-through, this is one of the few episodes to acknowledge how casually he's on the prowl; the script isn't totally clear, but as Gazzara plays the scene, it sounds like the Christmas engagement he has to break is with another random hook-up. Gazzara's natural pensiveness makes him the perfect foil for the voluble Borgnine; the script never requires Bryan to call bullshit on Harry's self-deceptive posturing, because the mix of amusement and pity playing across Gazzara's face makes it plain that he knows the score.
Directed by Michael Ritchie, soon to make acclaimed films like Downhill Racer and Smile, "Time and a Half" pushes the limits of how much visual creativity could be expressed on the Universal backlot. Nearly all of the episode takes place at night, and the interiors are dark too, punctuated by pools of harsh artificial light that prove just as gloomy as the shadows. (John L. Russell, who shot Psycho for Hitchcock and who would be dead before Christmas dawned in 1967, was the cinematographer.) At least half a dozen familiar carols adorn the soundtrack, either as instrumentals or source music, and seasonal iconography – wrapped gifts, Christmas trees, lights on suburban houses – abounds, all with a conscious sense of rubbing it in. The relentlessly Christmassy atmosphere is ironic, not festive. Never sour or hostile, "Time and a Half on Christmas Eve " is a still a pretty morose sort of holiday fable. It's Christmas from the point of view of the outsiders and introverts who will never be a part of the warmth and inclusiveness that most of television's Christmases take as a given.
The best thing about "Time and a Half" is that it's not a departure from the series' premise but an ideal realization of it. At its outset, Run For Your Life proposed a quest of self-discovery. It was a show about a dying man who wants to figure out how to live – a great concept that allowed for Hemingwayesque excursions into physical daring, but also promised introspection. In practice, of course, introspection is hard to pull off in prime time. Run For Your Life never wholly abandoned its existential side, but too often it slid into espionage stories and other generic action formulas. "Time and a Half on Christmas Eve" is one of the few episodes that omits any element of physical danger whatsoever, an exception it was probably able to claim only because it was a Christmas episode. Run For Your Life should have been that kind of show every week – but Huggins and Company only got away with it once, when all the flights were grounded.
Although it's been shown on RTV recently and there's a short clip on YouTube, "Time and a Half on Christmas Eve" remains hard to find. In the meantime, you might cue up the Bill Murray special A Very Murray Christmas – a new classic with an air of melancholy that reminded me of this episode.
Filed in The 100 Greatest Episodes
Tags: Ben Gazzara, Christmas episodes, Ernest Borgnine, Michael Ritchie, Run For Your Life
Ben and Zal
Few things are as obnoxious as an obit think-piece, a lazy essay that tries to force connections between two people who happened to die around the same time. But Ben Gazzara and Zalman King died on the same date – yesterday, February 3, both from cancer – and, dammit, they did have something important in common. Both of them, at least during the brief periods of their respective careers in which they were television series headliners, were passive actors who cultivated a stillness at the center of activity. They suppressed their egos in a way that only a few television stars have had the courage to try: William Peterson, in C.S.I.; David Duchovny (who had, crucially, been directed by King on Red Shoe Diaries), in the early seasons of The X-Files; and of course David Janssen, in everything he ever did.
The job of a television star is not to recede; it's to reach out and grab the viewer, to be the entry point into a new world and then the object of familiarity that encourages a weekly return. Gazzara, in Arrest and Trial (1963-1964) and Run For Your Life (1965-1968), and King, in The Young Lawyers (1970-1971), went against the grain. Their instinct was always to underplay, to count on their magnetism to draw you in toward the subtle detail work they were doing.
A cops-and-lawyers procedural with an unwieldly premise, Arrest and Trial stands out, in retrospect, as a science experiment in clashing acting styles. It pitted Gazzara, an acclaimed young Broadway actor associated with Strasberg, Kazan, and Tennessee Williams, against ex-baseball player Chuck Connors, an impossibly jut-jawed TV western star who never did an acting exercise in his life. In Arrest and Trial, Connors was likably stolid – the Rifleman in a suit – but Gazzara was mesmerizing. He was perhaps the first American television star with the courage to use each episode as his own sandbox to play in, exploring the stories and the inner life of his character with a Brando-esque curiosity, rather than aiming to mold a consistent, familiar genre archetype (in this case, the brilliant detective who always gets his man). This was the short-lived New Frontier moment of the liberal TV cop, and Gazzara played Detective Anderson's police interrogation scenes not as an inquisitor but like a psychiatrist or an oral historian. Most television stars step out into the lights with a story to tell; Gazzara said to the guest stars, tell me your story. And to the audience: project yourselves onto me.
Roy Huggins's Run For Your Life cast Gazzara as Paul Bryan, a lawyer dying of an unspecified and symptomless illness, who decides to chuck his grey flannel suit and a live a boho life for his remaining days. Immediately the show ran away from that premise as fast as it could, plunking Gazzara's character down into a glut of recycled action and espionage stories. But there were moments, especially in the early episodes, where Paul Bryan strayed into some off-the-path locale or exotic subculture, and Gazzara just nailed the proto-New Agey bliss of exploration and transformation that Run For Your Life was fumbling toward. The pilot was about deep sea diving and it was called "Rapture at 240," and how many other sixties television actors could and would play rapture? Gazzara derided both series in his autobiography, with some justification; he felt that this flirtation with mainstream stardom delayed his more important work for the independent filmmakers like John Cassavetes and Peter Bogdanovich. In their films, Gazzara moved into a more operatic mode, essaying epically flawed or doomed characters, especially in The Killing of a Chinese Bookie and Saint Jack. But even when a script required him to yell and scream and smash things, Gazzara never seemed to be overacting. "There was a quiet, understated nobility about him, earned the hard way, from the ground up," is how Video Watchdog editor Tim Lucas put it on Facebook yesterday.
Zalman King made his Hollywood debut as a teenaged thug in 1964's "Memo From Purgatory," a late episode of The Alfred Hitchcock Hour that Harlan Ellison also counts as his television debut (although that isn't quite accurate). A blonde, strapping James Caan played the Ellison figure in the autobiographical "Memo," but in my head I've always transmogrified King – diminutive, quick, Jewish, transparently intelligent – into Ellison's television avatar. The writer and the actor became lifelong friends; when we spoke about King years ago, Ellison referred to him affectionately as "Zally."
A year later, on The Munsters, King played a bearded beatnik (sample dialogue: "Man, that cat is deep"). At twenty-three, he was already typed (happily, I suspect) as an outsider, a kook. It was an inspired choice when King was cast as the most prominent of The Young Lawyers, a trio of eager law students who represented the poor and disenfranchised under the supervision of a grizzled Legal Aid lawyer. Top-billed Lee J. Cobb played the old lawyer, never overdoing it but still fulsomely dyspeptic and a formidable font of wisdom. King stole the show from him. He was one of the most open actors of his generation. As Gazzara had, King projected an empathy that worked beautifully within the context of this do-gooder show. King's character was written as a young hothead, a generation-gap foil for Cobb; but King brought to the role a plausible and only semi-scripted gravitas, a provocative rebuke to the assumption of unidirectional communication between young and old. Sixties TV was full of fake hippies – beaded sellouts like The Mod Squad – but King slipped one in under the radar, creating an intellectual, atypical anti-establishment figure. His Aaron Silverman was not some flaky peace-sign thrower; he was a fast-thinking, urban, Jewish liberal (really a radical, if you read between the lines), movingly and sincerely committed to change by challenging the system over and over again. Quick: Name another television character from the early seventies who fits that description.
The scripts on The Young Lawyers were pretty good (Ellison contributed the best one, the searing anti-drug love story "The Whimper of Whipped Dogs"); but the ideas I'm describing came out more through King's extraordinarily expressive acting, the play of complex thinking and sincere compassion across his face. Just a glimmer there; then The Young Lawyers went away and it was back to Barnaby Jones, geriatric crime-solver, and Steve McGarrett, authoritarian prick, and Richard Nixon, not a crook.
King was a minor movie star throughout the seventies, accruing credits that are impressively consistent in their status as either arty cult films (Some Call It Loving) or exploitation (Trip With the Teacher) or a fusion of both (Blue Sunshine). Then he began directing and producing; I haven't seen much of that work, but the Showtime series Red Shoe Diaries was a big enough hit to make King a rather disreputable household name, a middle-aged soft-core pornographer at whom one was encouraged to laugh up one's sleeve. The Young Lawyers should be easier to see, and King should be remembered as one of the most unusual and exciting actors around during the seventies.
Filed in Obituaries
Tags: acting, Arrest and Trial, Ben Gazzara, Obituaries, Run For Your Life, The Young Lawyers, TV stars, Zalman King
Three Plays by Tennessee Williams
Back in April, the Criterion Collection released a welcome DVD of Sidney Lumet's fourth feature, The Fugitive Kind. An adaptation of Tennessee Williams's 1957 play Orpheus Descending, The Fugitive Kind is an underrated work, an atmospheric movie wrapped around a searing performance from Marlon Brando (who would never interpret Williams on film again).
But the major rediscovery in this release is an "extra," a one-hour live television drama called "Three Plays by Tennessee Williams," which aired as a segment of The Kraft Theatre on April 16, 1958, and has so far as I know been unavailable outside of museums and archives ever since. Last year Criterion released a box set of eight key live television dramas, which comprised canonical works like Paddy Chayefsky's "Marty" and Rod Serling's "Patterns." While it was delight to see these masterpieces in the limelight again, they had all been in circulation on cable and on videotape since the early eighties. The arrival of "Three Plays" implies a commitment to plow a little deeper into the vaults and unearth some classic television that's not only good but also rare. I'm not sure that Criterion quite understood what they had in "Three Plays" (for one thing, they've managed to spell the name of one of its stars, Ben Gazzara, incorrectly on the DVD packaging)*, and most reviewers of the disc have either brushed past the television segment or failed to contextualize it accurately. But all that matters is that it's out there for all of us to discover on our own.
"Three Plays," which appears in its entirety (except for the original commercial segments) in the Fugitive Kind release, comprises three one-act plays written by Tennessee Williams in the lean years before A Streetcar Named Desire established him as one of the essential American writers. Apart from Williams, the connection between "Three Plays" and The Fugitive Kind is the director of both, Sidney Lumet, who had a nuanced understanding of Williams's preoccupations and, crucially, his use of language. All three of the plays are unapologetically verbose, and Lumet's key contribution is to stage them so that nothing distracts from the almost unbroken exchanges of dialogue in each.
Between them, the three one-acts encapsulate many of Williams's recognizable motifs in an undiluted form: the naked emotionalism, the fragile female psyches, the decaying grandeur of the Old South, the complex depiction of nostalgia, and what Lumet calls "the destruction of our sensitive souls." They're an essential corollary for anyone who ranks the best cinematic adaptations of Williams (A Streetcar Named Desire, Baby Doll, Sweet Bird of Youth, The Night of the Iguana) among the most vital of American movies during the fifties and early sixties.
"Moony's Kid Don't Cry" opens the hour, either because it was the earliest of the plays chronologically, or because it features the cast's only marquee names: the graylisted Lee Grant and Gazzara, who had originated the role of Brick in the Broadway production of Cat on a Hot Tin Roof. Contemporary reviewers scolded Gazzara for overacting, and in "Moony" he does revel in full-on torn-shirt mode. The layer of self-conscious cool that would be an element in his great performances (in the films for Cassavetes and Bogdanovich) is nowhere in sight here, even though Gazzara had it down as early as Anatomy of a Murder, only a year later. "Moony" is bait for Method-haters, two sweaty people screeching at each other in a squalid room without pause, and if the exercise succeeds it's because Lumet positions the excess of Moony's and his wife's outbursts as the prelude to a single, gentle gesture at the finale.
"The Last of the Solid Gold Watches" is the weakest of the trio, a kind of get-off-my-lawn harangue delivered by Broadway actor Thomas Chalmers with a somber dignity that drags against the youthful vitality of the surrounding performances. Zina Bethune, only thirteen at the time, offers the best performance in "Three Plays," as the grotesquely-dressed Willie Starr, who lives in the ruins of her family home and clings to the treasured memory of her deceased older sister Alva. The technical limitations of live television catch up with "This Property Is Condemned," in that Bethune speaks so fast and so breathily that some of Williams's dialogue can't be caught by the studio microphone. Still, Lumet gets the point across, gradually peeling off the layers of Willie's monologue to reveal her as an unreliable narrator and a forlorn and tragic figure.
It's useful to compare Lumet's succinct vignette to the wreck of a movie directed by Sydney Pollack, which bears the title This Property Is Condemned but deviates from Williams's material to personify the unseen Alva in the form of Natalie Wood. The Willie Starr scene dramatized in "Three Plays" becomes an expository prologue, sandwiched in the middle of the opening credits. Pollack's staging of that scene, along a curve in a defunct railroad track, resembles Lumet's, despite the contrast between the film's sunny outdoor location and the TV production's cramped interior set. I suspect that Pollack had seen the Kraft Theatre, and he may have understood that even this bastardized remnant of Williams's play was better than any subsequent scene in his film. Mary Badham, Pollack's Willie Starr, is more hardened and less vulnerable than Bethune, so we have a record of two different and, I think, equally valid approaches to the character.
"To live is to change, to change is to live," says Tennessee Williams, in his live, on-camera introduction to "Three Plays." Understandably, Williams takes care to label these short works as early efforts, perhaps not up to the level of the famous plays and films for which viewers would know him. He also seems nervous, stepping on the announcer's intro with his first line and often looking upward at his cue cards. How did the Kraft Theatre land both Williams and his trio of short plays for this broadcast? The answer involves some television heavyweights, and much change of the sort to which Williams alludes.
Williams was a hot literary commodity in 1958, with a decade of important plays and movies to his credit and the film version of Cat on a Hot Tin Roof, starring Elizabeth Taylor, due in theaters in the fall. But Williams's plays were dense, and too adult to be a natural fit for television. Even in the "Three Plays," which have little overt sexual content, it's surprising that the suggestion of Willie's casual promiscuity comes through so clearly. The person who fought to bring "Three Plays" to television without a great deal of censorship or simplification seems to have been Robert Herridge, one of the great forgotten producers of the live era.
Herridge had passed briefly through prime time, with a summer stint on Studio One – summer was when the heavyweight TV producers fled sweltering Manhattan and let the "B" team take over for thirteen weeks. But he was known mainly for non-commercial programming that ran in the Sunday "cultural ghetto," minimalist dramas that echoed the style of avant-garde theater and documentaries showcasing the jazz and folk music for which Herridge had a passion. (Camera Three, The Seven Lively Arts, and The Robert Herridge Theatre were some of the umbrella titles for Herridge's programs.) On Kraft he was subordinate to David Susskind, a talent agent who had become a big wheel in the industry as a "packager" of television properties.
With live drama, and its own Television Theatre hour (which dated back to 1947), in their death throes, Kraft took a chance on bringing in a big wheel like Susskind. Someone, either Susskind or Kraft or Herridge, hatched the idea of adapting a series of important modern literary works on the KraftTheatre. The idea was to attract more talent, more publicity, more viewers than the usual Kraft fare of original, written-for-television dramas. These shows kicked of with "Three Plays" and also included "The Outcasts of Poker Flat," Hemingway's "Fifty Grand," Fitzgerald's "The Last of the Belles," and a two-part, Don Mankiewicz-scripted version of Robert Penn Warren's "All the King's Men" that Herridge partisan Nat Hentoff deemed "a far more seizing transformation of the book than Robert Rossen's screen version." Sidney Lumet, who had just been nominated for the Oscar for Twelve Angry Men and had his pick of television assignments, signed on to direct "Three Plays" and "All the King's Men."
Susskind, remembered today as a defender of quality television, was no philistine. He launched East Side / West Side and brought a number of other difficult plays and novels to television on the DuPont Show of the Month and Play of the Week. But Herridge was too far out for Susskind, who called him a "kook" and carped that Herridge "tried to substitute nonconformity of dress for talent." Herridge earned Susskind's lasting enmity by shouldering the senior producer aside on the Kraft shows, literally barring Susskind from some of the rehearsals. Susskind's staffers Jacqueline Babbin and Audrey Gellen, who worked on the DuPont Show and Play of the Week adaptations (sometimes fronting for blacklisted writers), are credited on "Three Plays" as story editors. But I would guess that whatever changes were made to Williams's text were done by Herridge, or by Williams himself with Herridge's input.
(Charles H. "Chiz" Schultz, late of Studio One, also appears in the credits of "Three Plays," as an associate producer. I have no idea whether he was attached to Susskind, Herridge, Kraft, or NBC at that point.)
What's fascinating about Kraft's experiment in literature is how short-lived it was. Susskind and Herridge may have produced as few as a half-dozen segments for Kraft, which morphed into the Kraft Mystery Theatre for the summer and dropped from high- to low-brow with adaptations of pulpy short stories (including a couple of Ed McBain's early 87th Precinct tales). In October of 1958, The Kraft Theatre went off the air for good.
I'd love to see Criterion follow up this release with a package of the other Susskind-produced Krafts, which survive. But to be honest, what I'd like even more is a collection of the lesser-known original dramas from the year or two preceding the Susskind shows. These were teleplays written by some of the finest writers of the late-live television era: James Leo Herlihy, James Lee Barrett, John Gay, Paul Monash, Will Lorin, David Davidson, Robert Crean, Richard DeRoy, Robert Van Scoyk, Alfred Brenner. Larry Cohen, only twenty and still in the army, contributed some of the Mystery scripts, and even Jack Klugman (yes, that Jack Klugman) wrote a couple. I'll bet an audit of those kinescopes would yield some fine, forgotten work.
Tennessee Williams, television host.
* Update, 6/24/2010: The original version of this piece also noted the misspelling of Gazzara's name on the Criterion website, which was corrected shortly after publication. Notes on sources: Sidney Lumet quote is from a video interview on the Fugitive Kind DVD; Nat Hentoff quote and some of the Robert Herridge background are from "A TV Exclusive! The Passion of Huckleberry Dracula," collected in The Nat Hentoff Reader (Da Capo, 2001).
Filed in The DVD Corner
Tags: 1958, Ben Gazzara, David Susskind, dramatic anthologies, DVD, DVD reviews, Kraft, Kraft Television Theatre, Kraft Theatre, Lee Grant, Live Television, Nat Hentoff, Robert Herridge, Sidney Lumet, Sydney Pollack, Tennessee Williams, This Property Is Condemned, Thomas Chalmers, Three Plays by Tennessee Williams, Zina Bethune
Arrest and Trial
Debuting today on the website is the last of the dispatches from the archives that got killfiled when the late, lamented Television Chronicles magazine received its cancellation notice back in 1998. It's a lengthy production history and critique of the hybrid 1963-64 police procedural-slash-courtroom drama Arrest and Trial, now remembered mainly as a footnote in TV history due to its structural resemblance to Law & Order.
As a footnote is arguably how Arrest and Trial should be remembered. It's not a classic on the order of East Side/West Side or The Invaders. When I took on the show, it was on the assumption that its blatant emulation of elements of Naked City (in the arrest half) and The Defenders (in the trial half) would mean it might rank alongside them. As I actually watched and wrote about Arrest and Trial, I realized that the attempt to combine the disparate virtues of those two classics had created something of a misshapen mess – and I wondered if the series was worth the amount of time and the number of words I'd devoted to it. But as Timeless Media began releasing Arrest and Trial on DVD last fall, it seemed like a good time for me (and perhaps my readers) to reconsider the series.
In polishing the piece a bit and revisiting some of the episodes, I've been reminded of the virtues that do make Arrest and Trial eminently watchable. Ben Gazzara was one of the most inventive actors of his generation, with an intimate technique well-suited to the small screen. The show's sizable budget permitted more location shooting than just about any other Universal TV production ever managed, and so Arrest and Trial offers a terrific tour of 1963 Los Angeles. (And as I know the city better now than I did ten years ago, I'd love to have time to watch the episodes again just to try to figure out where each one was filmed. If anyone Angelenos who are seeing the show on DVD care to, I hope they'll post some notes along those lines in the comments here.)
I was also struck by how Arrest and Trial's image of law enforcement is so far removed from both our actual and fictionally represented experiences that it's like something beamed in from another planet. The Civil Rights-era plainclothes detective (played by Gazzara) who heads up the first half of Arrest and Trial is not just soft-spoken and empathetic – the kind of guy whose shoulder you just want to lean your head on – he's also a frank advocate of the policeman as social worker and psychiatrist instead of head-buster. You can imagine how real-life cops of the twenty-first century would guffaw if they somehow found this program in their Netflix queues. Today our police have dropped all pretense of having a relationship with civilians that's anything but adversarial – and our cop shows and cop movies, both those that demonize and even those that glorify the police, get a visceral charge in depicting the collateral damage that their subjects inflict on anyone unlucky enough to get between a cop's foot and an ass that needs kicking. I live in a city where the police department has enacted blatantly unconstitutional policies against its citizens, over and over again, and been rewarded not with censure but with municipal and judicial approval. So seeing Arrest and Trial again after ten years moved me unexpectedly. It was a reminder of one way in which we've lost our way since the sixties. Or, if that's too naive, it's a depiction of a civic ideal that we might never have had – but that we should still be trying for.
To date Timeless Media has released two DVD collections of Arrest and Trial, containing 18 of the series' 30 episodes. Of the thirty, four episodes are essential: "Journey Into Darkness," "Funny Man With a Monkey," Sydney Pollack's "The Quality of Justice," and "The Revenge of the Worm." Thus far only the first two are available among the DVDs, so one hopes a third volume will emerge.
If you make it all the way to the end, don't neglect the episode guide, which contains a lot of wonky trivia – episode budgets, shooting dates, unused episode titles, uncredited writers and actors – gleaned from the series' production files.
Filed in TV Series
Tags: Arrest and Trial, Ben Gazzara, Classic Television, police, Television Chronicles, Television History, TV History

redpajama_set_name: RedPajamaCommonCrawl


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Broward Bulldog Inc., doing business as the Florida Bulldog, is a nonprofit, independent and nonpartisan news organization that seeks to provide authoritative reporting in the public interest while upholding high standards of fairness and accuracy. We endorse the Code of Ethics of the Society of Professional Journalists. You can see the code here: http://www.spj.org/ethicscode.asp
Broward Bulldog's board of directors also has approved a financial conflict of interest policy (below) regarding its directors, principal officers and other "interested persons."
BROWARD BULLDOG, INC.
I. Purpose
The purpose of the conflicts of interest policy is to protect the interest of Broward Bulldog, Inc. (the "Company") when it is contemplating entering into a transaction or arrangement that might benefit the private interest of an officer or director of the Company. This policy is intended to supplement but not replace any applicable state laws governing conflicts of interest applicable to nonprofit and charitable corporations. Accordingly, in addition to the requirements of Section 617.0832 of the Florida Not For Profit Corporation Act, the following shall be complied with.
II. Definitions
"Interested Person" means any director, principal officer, or member of a committee with board-delegated powers who has a direct or indirect Financial Interest, as defined below, is an Interested Person.
"Financial Interest" means a person has a Financial Interest if the person has, directly or indirectly, through business, investment or family:
(a) an ownership or investment interest in any entity with which the Company has a transaction or arrangement, or
(b) a compensation arrangement with the Company or with any entity or individual with which the Company has a transaction or arrangement, or
(c) a potential ownership or investment interest in, or compensation arrangement with, any entity or individual with which the Company is negotiating a transaction or arrangement.
Compensation includes direct and indirect remuneration as well as gifts or favors that are substantial in nature.
A is not necessarily a conflict of interest. Under Article III, Section 2, a person with a Financial Interest has a conflict of interest only if the appropriate board or committee decides that a conflict of interest exists.
"Other Interests" means that a director, principal officer, or member of a committee with board-delegated powers shall not be deemed to have a direct or indirect Financial Interest solely because that person is an officer, director, member or potential program beneficiary of a not-for-profit entity that is applying to the Company for a grant or other support.
III. Procedures
1. Duty to Disclose In connection with any actual or possible conflicts of interest, an Interested Person must disclose the existence and nature of his or her Financial Interest and must be given the opportunity to disclose all material facts to the directors and members of committees with board-delegated powers considering the proposed transaction or arrangement. To avoid any appearance of impropriety or favoritism on the part of the Company, a person having any other interest in an applicant entity as described in Article II, Section 3, must disclose the existence and nature of that interest before participating in any discussion of, or vote on, potential Company support for that applicant; but the existence of such an interest alone shall not prevent him or her from subsequently discussing or voting on Company actions relating to that applicant.
2. Determining Whether a Conflict of Interest Exists. After disclosure of the Financial Interest and all material facts, and after any discussion with the Interested Person, he/she shall leave the board or committee meeting while the Financial Interest is discussed and voted upon. The remaining board or committee members shall decide if a conflict of interest exists.
3. Procedures for Addressing the Conflict of Interest.
(a) An Interested Person may make a presentation at the board or committee meeting, but after such presentation, he/she shall leave the meeting during the discussion of, and the vote on, the transaction or arrangement that results in the conflict of interest.
(b) The chairperson of the board or committee may, if appropriate, appoint a disinterested person or committee to investigate alternatives to the proposed transaction or arrangement.
(c) After exercising due diligence, the board or committee shall determine by a majority vote of the disinterested directors whether the transaction or arrangement is in the Company's best interest and for its own benefit and whether the transaction is fair and reasonable to the Company and shall make its decision as to whether to enter into the transaction or arrangement in conformity with such determination.
4. Violations of the Conflicts of Interest Policy.
(a) If the board or committee has reasonable cause to believe that a member has failed to disclose actual or possible conflicts of interest, it shall inform the member of the basis for such belief and afford the member an opportunity to explain the alleged failure to disclose.
(b) If, after hearing the response of the member and making such further investigation as may be warranted in the circumstances, the board or committee determines that the member has in fact failed to disclose an actual or possible conflict of interest, it shall take appropriate disciplinary and corrective action.
IV. Records of Proceedings
The minutes of the board and all committee with board-delegated powers shall contain:
(a) the names of the persons who disclosed or otherwise were found to have a Financial Interest in connection with an actual or possible conflict of interest, the nature of the Financial Interest, any action taken to determine whether a conflict of interest was present, and the board's or committee's decision as to whether a conflict of interest in fact existed.
(b) the names of the persons who were present for discussions and votes relating to the transaction or arrangement, the content of the discussion, including any alternatives to the proposed transaction or arrangement, and a record of any votes taken in connection therewith.
V. Compensation Committees
1. A voting member of the board of directors who receives compensation, directly or indirectly, from the Company for services is precluded from voting on matters pertaining to that member's compensation.
2. A voting member of any committee whose jurisdiction includes compensation matters and who receives compensation, directly or indirectly, from the Company for services is precluded from voting on matters pertaining to that member's compensation.
3. Directors who receive compensation, directly or indirectly, from the Company, whether as employees or independent contractors, are precluded from membership on any committee whose jurisdiction includes compensation matters. No director, either individually or collectively, is prohibited from providing information to any committee regarding employee or contractor compensation.
VI. Annual Statements
Each director, principal officer and member of a committee with board-delegated powers shall annually sign a statement which affirms that such person:
(a) has received a copy of the conflicts of interest policy,
(b) has read and understands the policy,
(c) has agreed to comply with the policy, and
(d) understands that the Company is a charitable organization and that in order to maintain its federal tax exemption it must engage primarily in activities which accomplish one or more of its tax-exempt purposes.
VII. Periodic Reviews
To ensure that the Company operates in a manner consistent with its charitable purposes and that it does not engage in activities that could jeopardize its status as an organization exempt from federal income tax, periodic reviews shall be conducted. The periodic reviews shall be conducted by the board, and at a minimum, include the following subjects:
(a) Whether compensation arrangements and benefits are reasonable and are the result of arm's-length bargaining.
(b) Whether partnership and joint venture arrangements and arrangements with other charities or for-profit providers of goods or services conform to written policies, are properly recorded, reflect reasonable payments, further the Company's charitable purposes and do not result in inurement or impermissible private benefit.
(c) Whether agreements to provide grants, loans and other forms of support further the Company's charitable purposes and do not result in inurement or impermissible private benefit.
VIII. Use of Outside Experts
In conducting the periodic reviews provided for in Article VII, the Company may, but need not, use outside advisors. If outside experts are used, their use shall not relieve the board of its responsibility for ensuring that periodic reviews are conducted.


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Fissure eruption of 2012-13
It was believed that after the major eruption of the Tolbachik volcano in 1975-76 it will need more than 200 years to accumulate the necessary amount of magma, which will be enough for a new large eruption. But early in the morning on November 27, 2012 there were registered small earthquakes at the depth of less than 5 kilometers under Tolbachik volcano.
Volcanologists did not even have enough time to warn of the impending eruption. In the evening, on the southern slope of Flat Tolbachik a crack opened, and a new eruption began.
In the early days it was impossible to see the details because of the bad weather. It was only on November 29 that the total crack length of about 3.5 km was revealed and its altitude of 1500-2000 meters. Along the crack numerous cinder cones formed, lava flowed from them. The height of the ejection bombs reached 200 meters. The ash cloud rose to the altitude of 60 kilometers. Lava flows paved clearings in the surrounding woods. The front of the advancing lava was 12 meters in height. Lava blocked the only road leading to Flat Tolbachik. Lava also destroyed the bases, located near Tolbachik.
By 30 November at each side of the crack there was left one active cone, which were named after famous Soviet volcanologists – A.A. Menyaylova and S.I. Naboko. On December 1, volcanic activity was concentrated on the southern tip of the crack. During such eruptions often a rapid reduction in the number of existing vent is observed: magma hardens quickly in a narrow crack and the eruption continues at the lowest portion of the breakthrough where the maximum pressure of the magma exists. In the crater of the cone named after Naboko there continuously flowed and splashed a small lava lake, throwing lumps of molten lava. Fast fiery stream of lava at the rate of 30-50 m3 / s flowed out of the lake on the slopes of the volcano. The speed of the lava was 2-3 m/s, and temperature 1060-1080°C. By mid-December the flow length was 17 kilometers. After that, the lava stopped and the lava field begn to increase its thickness.
It seems that the eruption stopped in January 2013, the volcanic activity became more flat and began to resemble the Southern breakthrough in 1976. The height of the ejection of volcanic bombs dropped to 100 meters. The lava began to flow from the tunnels several meters in diameter and with the length of 1-2 kilometers. By the end of May the lava flow decreased to 15 m³/s.
During the summer the lava flow level dropped. On August 23 the lava lake in the cone disappeared. In the explosive activity of the crater there were several dormant breaks of up to three days. However, in September, volcanic emissions from the two vents on the bottom of the crater showed that volcanic activity had not stopped.
Tolbachik erupted for more than nine months. The volume of lava stream is not precisely defined, but, according to preliminary estimates, it is about 0,5 km³ of lava. Such eruptions rarely occur in the world, and for Kamchatka, certainly it is one of the most significant eruptions in its historical period.
Trekking around the Tolbachik volcano The route of this tour runs through the territory of the Klyuchevskoy Nature Park that is included into the World Herita... Klyuchevskoy Park. Volcanoes Avachinsky, Mutnovsky. Esso The route of this tour runs along the most famous volcanoes of Kamchatka: the highest active volcano of Eurasia – Klyu... Kurile Lake. Volcanoes Gorely, Mutnovsky, Avacha and Tolbachik We would like to offer you tour to the extraordinary by its beauty Kuril Lake, where you are to watch the brown bear ...


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We love cities!
A love letter to the city! It might sound a little unusual, but it comes from the heart. The city is the source of our inspiration. Every location in the city has a history and its own unique story. Our ambition is to create a fitting concept to carry that history forward into the future. Not alone, but in partnership with policymakers, investors, businesses, property owners and local residents. With this approach we deliver projects that make a real difference for the city.
SENS, a passionate team
Open, inquisitive, creative and always surprising. People with a simple love of cities and a passion for their profession. We are an important partner in many development and regeneration projects for institutional and private investors from the Netherlands and elsewhere. We operate in the urban areas of the Netherlands, with a focus on the economic powerhouse of the greater Randstad conurbation. Our varied portfolio includes projects that embody every characteristic and aspect of a city: homes, shops, hotels, leisure, offices and parking.
Jan Willem Steenbergen
"The greatest challenges resides in the translation of a development vision into reality whilst ensuring that the needs of involved stakeholders are met."
Jaap Beekman
"The secret to a successful inner-city development is to address the challenges together from the very beginning".
Frank Veen
Developer (external)
"Make beautiful places, see happy people. Preferably making a big impact with a surprising intervention!"
Lisa Bloem
"Contracts and knowledge of the law are essential, but genuine success is built on cooperation and mutual trust".
Anne van Kralingen
"With the given contours and appropriate guts, we aim to connect and optimize the strengths and qualities of a city. That is the art and joy of our profession".
Gert-Jan Kloos
"Now that I'm an intern at SENS real estate I am very excided to not only develop myself, but also a piece of the Netherlands".
Timo Colsen
Gideon Goedhart
"Taking projects forward and connecting knowledge, while enjoying our work together: that's what gives me energy!".
Werner Loppies
"Anyone is able to contribute in his or her living environment. But only with passion, guts and proactive collaboration can we find the right building blocks to turn our dreams into reality."
Gert Jan Smit
"My ambition is to improve and strengthen a city's existing appeal with a careful mix of building density, green space and ambitious sustainable development in the inner city".
Yvette Klein
Project and Office Support
"People are giving the city soul and identity".
Gerad Schoenaker
"If you can imagine it, you can create it. It is a question of using all of your creativity and imagination to convince stakeholders to join you in creating something of lasting value".
Twan Briels
"Creating places where people come together, and with this making the city a vibrant place to live. That is my aspiration'."
Abdel Salemi
"The part I like most about my work is the moment when the project is completed and the people of the city start using the location as though it had never been forgotten".
Steven Zijlstra
"Collectively improve the existing living environment, in order to obtain sustainable joy. That is what I want to achieve".