• Nolan Kincaid posted an update 6 months, 2 weeks ago

    The linear no-threshold (LNT) model has historically been the default assumption in assessing carcinogenic risk from arsenic ingestion based on epidemiological studies. This contrasts with the threshold model used in assessing carcinogenic risk from arsenic ingestion derived from toxicological investigations of experimental animals. We present here a review of our epidemiological work that has examined models that may better explain the human cancer risk from the ingestion of arsenic, particularly from low level exposures, than does the LNT model. While previous epidemiology studies have demonstrated increased risks of bladder, lung, and skin cancers at arsenic exposures of 200 ug/L or greater, we seek here to examine the dose-response patterns at lower exposure levels. These include ecological, case/control, and cohort designs. Methodologic issues include choice of continuous or stratified analysis of exposure data, search for sources of non-conformity or variability, and distinctions in water sources and geography. Multiple studies have yielded useful data-based models, including threshold models, hockey-stick models, and “J-shaped” linear-quadratic models. These models have found that increased cancer risk may only begin at specific arsenic exposure levels greater than zero. These results provide guidance in seeking toxicological explanations and public health reference levels.Nociceptive stimulation is predicted to uniformly inhibit motoneurone pools of painful muscles and those producing painful movements. Although reduced motoneurone discharge rate during pain provides some evidence, recent data show evidence of increased excitability of some motoneurones. These observations suggest non-uniform effects of nociception on motoneurone excitability. More direct measures are required, but this is difficult to assess as few measures enable in vivo evaluation of motoneurone excitability in humans. We investigated changes in motoneurone excitability during experimental pain using two methods in separate experiments (i) estimation of the time-course of motoneurone afterhyperpolarization (AHP) from interval death rate analysis of interspike intervals of single motor unit discharge; and (ii) probability of early motoneurone discharge to a descending volley excited using transcranial magnetic stimulation (TMS). Tibialis anterior motor units were recorded with fine-wire electrodes before, during and after painful infusion of 5% hypertonic saline into the muscle. Activation of 17 units (16 participants) could be used for AHP analysis. learn more show shortened (n = 11) and lengthened (n = 6) AHP time-course. Increased (n = 6) and decreased (n = 6) probability of early motoneurone discharge were observed in the TMS experiment. These convergent observations suggest non-uniform effects of nociceptive stimulation on motoneurone pools. This does not support the hypothesis that nociceptive input induces uniform inhibition of painful muscle. Instead, interpretation of results implies redistribution of activity between motor units, with possible benefit for unloading painful tissues. This finding supports an interpretation that differs from the generally accepted view in pain physiology regarding adaptation to motor function in pain.Inflammasomes are key components of the innate immune system and activation of these multiprotein platforms is a crucial event in the etiopathology of amyotrophic lateral sclerosis (ALS). Inflammasomes consist of a pattern recognition receptor (PRR), the adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) and caspase 1. Exogenous or endogenous “danger signals” can trigger inflammasome assembly and promote maturation and release of pro-inflammatory cytokines, including interleukin 1β. Previous studies have demonstrated presence and activation of NLRP3 in spinal cord tissue from SOD1(G93A) mice and human sporadic ALS (sALS) patients. However, regulation and cell type-specific localization of other well-known PRRs has not yet been analysed in ALS. Here, we explored gene expression, protein concentration and cell type-specific localization of the NLRP1, NLRC4 and AIM2 inflammasomes in spinal cord samples from SOD1(G93A) mice and sALS patients. Transcription levels of NLRP1 and NLRC4, but not AIM2, were elevated in symptomatic SOD1(G93A) animals. Immunoblotting revealed elevated protein levels of NLRC4, which were significantly increased in sALS vs. #link# control patients. Immunofluorescence studies revealed neuronal labelling of all investigated PRRs. Staining of AIM2 was detected in all types of glia, whereas glial type-specific labelling was observed for NLRP1 and NLRC4. Our findings revealed pathology-related and cell type-specific differences in the expression of subsets of PRRs. Besides NLRP3, NLRC4 appears to be linked more closely to ALS pathogenesis.Since the onslaught of SARS-CoV-2, the research community has been searching for a vaccine to fight against this virus. However, during this period, the virus has mutated to adapt to the different environmental conditions in the world and made the task of vaccine design more challenging. In this situation, the identification of virus strains is very much timely and important task. We have performed genome-wide analysis of 10664 SARS-CoV-2 genomes of 73 countries to identify and prepare a Single Nucleotide Polymorphism (SNP) dataset of SARS-CoV-2. Thereafter, with the use of this SNP data, the advantage of hierarchical clustering is taken care of in such a way so that Average Linkage and Complete Linkage with Jaccard and Hamming distance functions are applied separately in order to identify the virus strains as clusters present in the SNP data. In this regard, the consensus of both the clustering results are also considered while Silhouette index is used as a cluster validity index to measure the goodness of tur due to the absence of any non-synonymous signature SNPs. In addition to all these, the code, SNP dataset, 10664 labelled SARS-CoV-2 strains and additional results as supplementary are provided through our website for further use.

All content contained on CatsWannaBeCats.Com, unless otherwise acknowledged,is the property of CatsWannaBeCats.Com and subject to copyright.

CONTACT US

We're not around right now. But you can send us an email and we'll get back to you, asap.

Sending

Log in with your credentials

or    

Forgot your details?

Create Account