The Clinical Implications of Fatty Pancreas: A Concise Review

Abstract

Fatty pancreas is a newly recognized condition which is poorly investigated until today as compared to nonalcoholic fatty liver disease. It is characterized by pancreatic fat accumulation and subsequent development of pancreatic and metabolic complications. Association of fatty pancreas have been described with type 2 diabetes mellitus, acute and chronic pancreatitis and even pancreatic carcinoma. In this review article, we provide an update on clinical implications, pathogenesis, diagnosis, treatment and outcomes.

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AICAR prevents fat gain following the cessation of voluntary physical activity

Abstract

The transition from physical activity to inactivity is associated with drastic increases in 'catch-up' fat that in turn foster the development of many obesity-associated maladies. We tested if 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) treatment would prevent gains in body fat following the sudden transition from a physically active state to an inactive state by locking a voluntary running wheel. Male, Wistar rats were either sedentary (SED), or given wheel access for 4 weeks, at which time rats with wheels continued running (RUN), either had their wheel locked (WL), or had WL with daily AICAR injection (WL + AICAR) for 1 week. RUN and WL + AICAR prevented gains in body fat compared to SED and WL (P < 0.001). Cyclin A1 mRNA, a marker of cell proliferation, was decreased in omental (OMAT), but not subcutaneous (SAT) adipose tissue, in RUN and WL + AICAR compared to SED and WL (P < 0.05). Both cyclin A1 mRNA and protein positively associated with gains in fat mass (P < 0.05). Cyclin A1 mRNA in OMAT, but not SAT, negatively correlated with p-AMPK levels (P < 0.05). Differences in fat gain and OMAT mRNA and protein levels were independent of changes in food intake and in differences in select hypothalamic mRNAs. These findings suggest that AICAR treatment prevents acute gains in adipose tissue following physical inactivity to levels of rats that continuously run, and that together continuous physical activity and AICAR could, at least initially under these conditions, exert similar inhibitory effects on adipogenesis in a depot-specific manner.

This article is protected by copyright. All rights reserved

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Molecular Epidemiology of Carbapenem-Resistant Acinetobacter baumannii in a Tertiary Care Hospital in Egypt: Clonal Spread of blaOXA-23

Microbial Drug Resistance , Vol. 0, No. 0.


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Characterization of Livestock-Associated Methicillin-Resistant Staphylococcus aureus CC398 and mecC-positive CC130 from Zoo Animals in the United Kingdom

Microbial Drug Resistance , Vol. 0, No. 0.


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Molecular Characterization of Italian Isolates of Fluoroquinolone-Resistant Streptococcus agalactiae and Relationships with Chloramphenicol Resistance

Microbial Drug Resistance , Vol. 0, No. 0.


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Percutaneous Rupture of Zygapophyseal Joint Synovial Cysts: a Prospective Assessment of Nonsurgical Management

Although lumbar zygapophyseal joint synovial cysts are fairly well recognized, they are an uncommon cause of lumbosacral radicular pain. Non-operative treatments include percutaneous aspiration of the cysts under computed tomography or fluoroscopic guidance with a subsequent corticosteroid injection. However, there are mixed results in terms of long-term outcomes and cyst reoccurrence. This study prospectively evaluates percutaneous ruptures of zygapophyseal joint (Z-joint) synovial cysts for the treatment of lumbosacral radicular pain.

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Subacute Progressive Myelopathy: Transverse Myelitis or Subacute Combined Degeneration? A Case Report

Evolving subacute myelopathies have many possible etiologies. This is a report of a patient who presented with progressive paresthesias, proprioceptive loss, and gait disturbance with acute myelitis seen on Magnetic Resonance Imaging initially concerning for transverse myelitis. However, she also had vitamin B12 deficiency and her clinical course ultimately suggested a diagnosis more compatible with subacute combined degeneration. The clinical features, laboratory and imaging findings and prognosis of the two disorders are compared.

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Motor unit remodelling in multifocal motor neuropathy: the importance of axonal loss

To estimate the degree of axonal loss in patients diagnosed with multifocal motor neuropathy (MMN) using a novel assessment of motor unit numbers and size.

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Spotlight: Cloud PCR offers fast, intuitive EMS trip sheet charting for any device

Features like Google geo-locating, automatic clocking and integrated talk-to-type functionality reduces charting times by up to 70 percent

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Expression of Concern.

No abstract available

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Bayesian Networks Illustrate Genomic and Residual Trait Connections in Maize (Zea mays L.)

Relationships among traits were investigated on the genomic and residual levels using novel methodology. This included inference on these relationships via Bayesian networks and an assessment of the networks with structural equation models. The methodology employed three steps. First, a Bayesian multiple-trait Gaussian model was fitted to the data to decompose phenotypic values into their genomic and residual components. Second, genomic and residual network structures among traits were learned from estimates of these two components. Network learning was performed using six different algorithmic settings for comparison, of which two were score-based and four were constraint-based approaches. Third, structural equation model analyses ranked the networks in terms of goodness of fit and predictive ability, and compared them with the standard multiple-trait fully recursive network. The methodology was applied to experimental data representing the European heterotic maize pools Dent and Flint (Zea mays L.). Inferences on genomic and residual trait connections were depicted separately as directed acyclic graphs. These graphs provide information beyond mere pairwise genetic or residual associations between traits, illustrating for example conditional independencies and hinting at potential causal links among traits. Network analysis suggested some genetic correlations as potentially spurious. Genomic and residual networks were compared between Dent and Flint.

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Comparative Genomics of Two Sequential Candida glabrata Clinical Isolates

Candida glabrata is an important fungal pathogen which develops rapid antifungal resistance in treated patients. It is known that azole treatments lead to antifungal resistance in this fungal species and that multidrug efflux transporters are involved in this process. Specific mutations in the transcriptional regulator PDR1 result in upregulation of the transporters. In addition, we showed that the PDR1 mutations can contribute to enhance virulence in animal models. In this study, we were interested to compare genomes of two specific C. glabrata-related isolates, one of which was azole susceptible (DSY562) while the other was azole resistant (DSY565). DSY565 contained a PDR1 mutation (L280F) and was isolated after a time-lapse of 50 d of azole therapy. We expected that genome comparisons between both isolates could reveal additional mutations reflecting host adaptation or even additional resistance mechanisms. The PacBio technology used here yielded 14 major contigs (sizes 0.18–1.6 Mb) and mitochondrial genomes from both DSY562 and DSY565 isolates that were highly similar to each other. Comparisons of the clinical genomes with the published CBS138 genome indicated important genome rearrangements, but not between the clinical strains. Among the unique features, several retrotransposons were identified in the genomes of the investigated clinical isolates. DSY562 and DSY565 each contained a large set of adhesin-like genes (101 and 107, respectively), which exceed by far the number of reported adhesins (63) in the CBS138 genome. Comparison between DSY562 and DSY565 yielded 17 nonsynonymous SNPs (among which the was the expected PDR1 mutation) as well as small size indels in coding regions (11) but mainly in adhesin-like genes. The genomes contained a DNA mismatch repair allele of MSH2 known to be involved in the so-called hyper-mutator phenotype of this yeast species and the number of accumulated mutations between both clinical isolates is consistent with the presence of a MSH2 defect. In conclusion, this study is the first to compare genomes of C. glabrata sequential clinical isolates using the PacBio technology as an approach. The genomes of these isolates taken in the same patient at two different time points exhibited limited variations, even if submitted to the host pressure.

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The Accuracy and Bias of Single-Step Genomic Prediction for Populations Under Selection

In single-step analyses, missing genotypes are explicitly or implicitly imputed, and this requires centering the observed genotypes using the means of the unselected founders. If genotypes are only available for selected individuals, centering on the unselected founder mean is not straightforward. Here, computer simulation is used to study an alternative analysis that does not require centering genotypes but fits the mean $${\mu }_{g}$$ of unselected individuals as a fixed effect. Starting with observed diplotypes from 721 cattle, a five-generation population was simulated with sire selection to produce 40,000 individuals with phenotypes, of which the 1000 sires had genotypes. The next generation of 8000 genotyped individuals was used for validation. Evaluations were undertaken with (J) or without (N) $${\mu }_{g}$$ when marker covariates were not centered; and with (JC) or without (C) $${\mu }_{g}$$ when all observed and imputed marker covariates were centered. Centering did not influence accuracy of genomic prediction, but fitting $${\mu }_{g}$$ did. Accuracies were improved when the panel comprised only quantitative trait loci (QTL); models JC and J had accuracies of 99.4%, whereas models C and N had accuracies of 90.2%. When only markers were in the panel, the 4 models had accuracies of 80.4%. In panels that included QTL, fitting $${\mu }_{g}$$ in the model improved accuracy, but had little impact when the panel contained only markers. In populations undergoing selection, fitting $${\mu }_{g}$$ in the model is recommended to avoid bias and reduction in prediction accuracy due to selection.

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A Genetic Screen Reveals an Unexpected Role for Yorkie Signaling in JAK/STAT-Dependent Hematopoietic Malignancies in Drosophila melanogaster

A gain-of-function mutation in the tyrosine kinase JAK2 (JAK2^V617F) causes human myeloproliferative neoplasms (MPNs). These patients present with high numbers of myeloid lineage cells and have numerous complications. Since current MPN therapies are not curative, there is a need to find new regulators and targets of Janus kinase/Signal transducer and activator of transcription (JAK/STAT) signaling that may represent additional clinical interventions . Drosophila melanogaster offers a low complexity model to study MPNs as JAK/STAT signaling is simplified with only one JAK [Hopscotch (Hop)] and one STAT (Stat92E). hop^{Tumorous-lethal (Tum-l)} is a gain-of-function mutation that causes dramatic expansion of myeloid cells, which then form lethal melanotic tumors. Through an F1 deficiency (Df) screen, we identified 11 suppressors and 35 enhancers of melanotic tumors in hop^Tum-l animals. Dfs that uncover the Hippo (Hpo) pathway genes expanded (ex) and warts (wts) strongly enhanced the hop^Tum-l tumor burden, as did mutations in ex, wts, and other Hpo pathway genes. Target genes of the Hpo pathway effector Yorkie (Yki) were significantly upregulated in hop^Tum-l blood cells, indicating that Yki signaling was increased. Ectopic hematopoietic activation of Yki in otherwise wild-type animals increased hemocyte proliferation but did not induce melanotic tumors. However, hematopoietic depletion of Yki significantly reduced the hop^Tum-l tumor burden, demonstrating that Yki is required for melanotic tumors in this background. These results support a model in which elevated Yki signaling increases the number of hemocytes, which become melanotic tumors as a result of elevated JAK/STAT signaling.

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A High-Density Linkage Map Reveals Sexual Dimorphism in Recombination Landscapes in Red Deer (Cervus elaphus)

High-density linkage maps are an important tool to gain insight into the genetic architecture of traits of evolutionary and economic interest, and provide a resource to characterize variation in recombination landscapes. Here, we used information from the cattle genome and the 50 K Cervine Illumina BeadChip to inform and refine a high-density linkage map in a wild population of red deer (Cervus elaphus). We constructed a predicted linkage map of 38,038 SNPs and a skeleton map of 10,835 SNPs across 34 linkage groups. We identified several chromosomal rearrangements in the deer lineage relative to sheep and cattle, including six chromosome fissions, one fusion, and two large inversions. Otherwise, our findings showed strong concordance with map orders in the cattle genome. The sex-averaged linkage map length was 2739.7 cM and the genome-wide autosomal recombination rate was 1.04 cM/Mb. The female autosomal map length was 1.21 longer than that of males (2767.4 cM vs. 2280.8 cM, respectively). Sex differences in map length were driven by high female recombination rates in peri-centromeric regions, a pattern that is unusual relative to other mammal species. This effect was more pronounced in fission chromosomes that would have had to produce new centromeres. We propose two hypotheses to explain this effect: (1) that this mechanism may have evolved to counteract centromeric drive associated with meiotic asymmetry in oocyte production; and/or (2) that sequence and structural characteristics suppressing recombination in close proximity to the centromere may not have evolved at neo-centromeres. Our study provides insight into how recombination landscapes vary and evolve in mammals, and will provide a valuable resource for studies of evolution, genetic improvement, and population management in red deer and related species.

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Retrotransposons Are the Major Contributors to the Expansion of the Drosophila ananassae Muller F Element

The discordance between genome size and the complexity of eukaryotes can partly be attributed to differences in repeat density. The Muller F element (~5.2 Mb) is the smallest chromosome in Drosophila melanogaster, but it is substantially larger (>18.7 Mb) in D. ananassae. To identify the major contributors to the expansion of the F element and to assess their impact, we improved the genome sequence and annotated the genes in a 1.4-Mb region of the D. ananassae F element, and a 1.7-Mb region from the D element for comparison. We find that transposons (particularly LTR and LINE retrotransposons) are major contributors to this expansion (78.6%), while Wolbachia sequences integrated into the D. ananassae genome are minor contributors (0.02%). Both D. melanogaster and D. ananassae F-element genes exhibit distinct characteristics compared to D-element genes (e.g., larger coding spans, larger introns, more coding exons, and lower codon bias), but these differences are exaggerated in D. ananassae. Compared to D. melanogaster, the codon bias observed in D. ananassae F-element genes can primarily be attributed to mutational biases instead of selection. The 5' ends of F-element genes in both species are enriched in dimethylation of lysine 4 on histone 3 (H3K4me2), while the coding spans are enriched in H3K9me2. Despite differences in repeat density and gene characteristics, D. ananassae F-element genes show a similar range of expression levels compared to genes in euchromatic domains. This study improves our understanding of how transposons can affect genome size and how genes can function within highly repetitive domains.

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A SINE Insertion in ATP1B2 in Belgian Shepherd Dogs Affected by Spongy Degeneration with Cerebellar Ataxia (SDCA2)

Spongy degeneration with cerebellar ataxia (SDCA) is a genetically heterogeneous neurodegenerative disorder with autosomal recessive inheritance in Malinois dogs, one of the four varieties of the Belgian Shepherd breed. Using a combined linkage and homozygosity mapping approach we identified an ~10.6 Mb critical interval on chromosome 5 in a Malinois family with four puppies affected by cerebellar dysfunction. Visual inspection of the 10.6 Mb interval in whole-genome sequencing data from one affected puppy revealed a 227 bp SINE insertion into the ATP1B2 gene encoding the β₂ subunit of the Na⁺/K⁺-ATPase holoenzyme (ATP1B2:c.130_131insLT796559.1:g.50_276). The SINE insertion caused aberrant RNA splicing. Immunohistochemistry suggested a reduction of ATP1B2 protein expression in the central nervous system of affected puppies. Atp1b2 knockout mice had previously been reported to show clinical and neurohistopathological findings similar to the affected Malinois puppies. Therefore, we consider ATP1B2:c.130_131ins227 the most likely candidate causative variant for a second subtype of SDCA in Malinois dogs, which we propose to term spongy degeneration with cerebellar ataxia subtype 2 (SDCA2). Our study further elucidates the genetic and phenotypic complexity underlying cerebellar dysfunction in Malinois dogs and provides the basis for a genetic test to eradicate one specific neurodegenerative disease from the breeding population in Malinois and the other varieties of the Belgian Shepherd breed. ATP1B2 thus represents another candidate gene for human inherited cerebellar ataxias, and SDCA2-affected Malinois puppies may serve as a naturally occurring animal model for this disorder.

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Patterns of Genetic Structure and Linkage Disequilibrium in a Large Collection of Pea Germplasm

Pea (Pisum sativum, L.) is a major pulse crop used both for animal and human alimentation. Owing to its association with nitrogen-fixing bacteria, it is also a valuable component for low-input cropping systems. To evaluate the genetic diversity and the scale of linkage disequilibrium (LD) decay in pea, we genotyped a collection of 917 accessions, gathering elite cultivars, landraces, and wild relatives using an array of ~13,000 single nucleotide polymorphisms (SNP). Genetic diversity is broadly distributed across three groups corresponding to wild/landraces peas, winter types, and spring types. At a finer subdivision level, genetic groups relate to local breeding programs and type usage. LD decreases steeply as genetic distance increases. When considering subsets of the data, LD values can be higher, even if the steep decay remains. We looked for genomic regions exhibiting high level of differentiation between wild/landraces, winter, and spring pea, respectively. Two regions on linkage groups 5 and 6 containing 33 SNPs exhibit stronger differentiation between winter and spring peas than would be expected under neutrality. Interestingly, QTL for resistance to cold acclimation and frost resistance have been identified previously in the same regions.

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Genome-Wide Associations for Water-Soluble Carbohydrate Concentration and Relative Maturity in Wheat Using SNP and DArT Marker Arrays

Improving water-use efficiency by incorporating drought avoidance traits into new wheat varieties is an important objective for wheat breeding in water-limited environments. This study uses genome wide association studies (GWAS) to identify candidate loci for water-soluble carbohydrate accumulation—an important drought-avoidance characteristic in wheat. Phenotypes from a multi-environment trial with experiments differing in water availability and separate single nucleotide polymorphism (SNP) and diversity arrays technology (DArT) marker sets were used to perform the analyses. Significant associations for water-soluble carbohydrate accumulation were identified on chromosomes 1A, 1B, 1D, 2D, and 4A. Notably, these loci did not collocate with the major loci identified for relative maturity. Loci on chromosome 1D collocated with markers previously associated with the high molecular weight glutenin Glu-D1 locus. Genetic x environmental interactions impacted the results strongly, with significant associations for carbohydrate accumulation identified only in the water-deficit experiments. The markers associated with carbohydrate accumulation may be useful for marker-assisted selection of drought tolerance in wheat.

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A High-Density Genetic Linkage Map and QTL Fine Mapping for Body Weight in Crucian Carp (Carassius auratus) Using 2b-RAD Sequencing

A high-resolution genetic linkage map is essential for a wide range of genetics and genomics studies such as comparative genomics analysis and QTL fine mapping. Crucian carp (Carassius auratus) is widely distributed in Eurasia, and is an important aquaculture fish worldwide. In this study, a high-density genetic linkage map was constructed for crucian carp using 2b-RAD technology. The consensus map contains 8487 SNP markers, assigning to 50 linkage groups (LGs) and spanning 3762.88 cM, with an average marker interval of 0.44 cM and genome coverage of 98.8%. The female map had 4410 SNPs, and spanned 3500.42 cM (0.79 cM/marker), while the male map had 4625 SNPs and spanned 3346.33 cM (0.72 cM/marker). The average recombination ratio of female to male was 2.13:1, and significant male-biased recombination suppressions were observed in LG47 and LG49. Comparative genomics analysis revealed a clear 2:1 syntenic relationship between crucian carp LGs and chromosomes of zebrafish and grass carp, and a 1:1 correspondence, but extensive chromosomal rearrangement, between crucian carp and common carp, providing evidence that crucian carp has experienced a fourth round of whole genome duplication (4R-WGD). Eight chromosome-wide QTL for body weight at 2 months after hatch were detected on five LGs, explaining 10.1–13.2% of the phenotypic variations. Potential candidate growth-related genes, such as an EGF-like domain and TGF-β, were identified within the QTL intervals. This high-density genetic map and QTL analysis supplies a basis for genome evolutionary studies in cyprinid fishes, genome assembly, and QTL fine mapping for complex traits in crucian carp.

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Fine Mapping, Transcriptome Analysis, and Marker Development for Y2, the Gene That Conditions {beta}-Carotene Accumulation in Carrot (Daucus carota L.)

Domesticated carrots, Daucus carota subsp. sativus, are the richest source of β-carotene in the US diet, which, when consumed, is converted into vitamin A, an essential component of eye health and immunity. The Y₂ locus plays a significant role in beta-carotene accumulation in carrot roots, but a candidate gene has not been identified. To advance our understanding of this locus, the genetic basis of β-carotene accumulation was explored by utilizing an advanced mapping population, transcriptome analysis, and nucleotide diversity in diverse carrot accessions with varying levels of β-carotene. A single large effect Quantitative Trait Locus (QTL) on the distal arm of chromosome 7 overlapped with the previously identified β-carotene accumulation QTL, Y₂. Fine mapping efforts reduced the genomic region of interest to 650 kb including 72 genes. Transcriptome analysis within this fine mapped region identified four genes differentially expressed at two developmental time points, and 13 genes differentially expressed at one time point. These differentially expressed genes included transcription factors and genes involved in light signaling and carotenoid flux, including a member of the Di19 gene family involved in Arabidopsis photomorphogenesis, and a homolog of the bHLH36 transcription factor involved in maize carotenoid metabolism. Analysis of nucleotide diversity in 25 resequenced carrot accessions revealed a drastic decrease in diversity of this fine-mapped region in orange cultivated accessions as compared to white and yellow cultivated and to white wild samples. The results presented in this study provide a foundation to identify and characterize the gene underlying β-carotene accumulation in carrot.

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A Duplicated, Truncated amh Gene Is Involved in Male Sex Determination in an Old World Silverside

A master sex-determining gene, the Y chromosome-linked anti-Müllerian hormone (amhy) gene, has been described in two New World atheriniform species but little is known on the distribution, evolution, and function(s) of this gene in other Atheriniformes. Interestingly, amhy has been found to coexist with temperature-dependent sex determination (TSD), providing a unique opportunity to explore the interplay between genotypic and environmental sex determination. In this study, the search for an amhy homolog was extended to an Old World atheriniform, the cobaltcap silverside Hypoatherina tsurugae (Atherinidae). The full sequences, including the coding and noncoding regions, of the autosomal amh (amha) and a putative amhy were obtained. The deduced Amha and Amhy proteins comprised 511 and 340 amino acids (aa), respectively. PCR analysis with genomic DNA from wild adults and from laboratory-reared juveniles revealed a high, but not complete association of ~95% between amhy and maleness. The spatiotemporal expression of amhy and amha during gonadal sex differentiation was analyzed by qRT-PCR and in situ hybridization (ISH). amhy transcription (in amhy-positive larvae) started before and peaked during histological differentiation of the gonads whereas amha was negligible during the same period in both genotypes. These results demonstrate that the amhy, although with some structural differences in relation to the amhy of some New World atheriniforms, is strongly associated with maleness and probably important for testicular development in this Old World atheriniform. Thus, amhy is a candidate sex determination gene in cobaltcap silverside and it will be key to scrutinize the mechanism of sex determination in this species.

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Simple Expression Domains Are Regulated by Discrete CRMs During Drosophila Oogenesis

Eggshell patterning has been extensively studied in Drosophila melanogaster. However, the cis-regulatory modules (CRMs), which control spatiotemporal expression of these patterns, are vastly unexplored. The FlyLight collection contains >7000 intergenic and intronic DNA fragments that, if containing CRMs, can drive the transcription factor GAL4. We cross-listed the 84 genes known to be expressed during D. melanogaster oogenesis with the ~1200 listed genes of the FlyLight collection, and found 22 common genes that are represented by 281 FlyLight fly lines. Of these lines, 54 show expression patterns during oogenesis when crossed to an UAS-GFP reporter. Of the 54 lines, 16 recapitulate the full or partial pattern of the associated gene pattern. Interestingly, while the average DNA fragment size is ~3 kb in length, the vast majority of fragments show one type of spatiotemporal pattern in oogenesis. Mapping the distribution of all 54 lines, we found a significant enrichment of CRMs in the first intron of the associated genes' model. In addition, we demonstrate the use of different anteriorly active FlyLight lines as tools to disrupt eggshell patterning in a targeted manner. Our screen provides further evidence that complex gene patterns are assembled combinatorially by different CRMs controlling the expression of genes in simple domains.

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A Kinome RNAi Screen in Drosophila Identifies Novel Genes Interacting with Lgl, aPKC, and Crb Cell Polarity Genes in Epithelial Tissues

In both Drosophila melanogaster and mammalian systems, epithelial structure and underlying cell polarity are essential for proper tissue morphogenesis and organ growth. Cell polarity interfaces with multiple cellular processes that are regulated by the phosphorylation status of large protein networks. To gain insight into the molecular mechanisms that coordinate cell polarity with tissue growth, we screened a boutique collection of RNAi stocks targeting the kinome for their capacity to modify Drosophila "cell polarity" eye and wing phenotypes. Initially, we identified kinase or phosphatase genes whose depletion modified adult eye phenotypes associated with the manipulation of cell polarity complexes (via overexpression of Crb or aPKC). We next conducted a secondary screen to test whether these cell polarity modifiers altered tissue overgrowth associated with depletion of Lgl in the wing. These screens identified Hippo, Jun kinase (JNK), and Notch signaling pathways, previously linked to cell polarity regulation of tissue growth. Furthermore, novel pathways not previously connected to cell polarity regulation of tissue growth were identified, including Wingless (Wg/Wnt), Ras, and lipid/Phospho-inositol-3-kinase (PI3K) signaling pathways. Additionally, we demonstrated that the "nutrient sensing" kinases Salt Inducible Kinase 2 and 3 (SIK2 and 3) are potent modifiers of cell polarity phenotypes and regulators of tissue growth. Overall, our screen has revealed novel cell polarity-interacting kinases and phosphatases that affect tissue growth, providing a platform for investigating molecular mechanisms coordinating cell polarity and tissue growth during development.

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Sex Chromosome Evolution, Heterochiasmy, and Physiological QTL in the Salmonid Brook Charr Salvelinus fontinalis

Whole-genome duplication (WGD) can have large impacts on genome evolution, and much remains unknown about these impacts. This includes the mechanisms of coping with a duplicated sex determination system and whether this has an impact on increasing the diversity of sex determination mechanisms. Other impacts include sexual conflict, where alleles having different optimums in each sex can result in sequestration of genes into nonrecombining sex chromosomes. Sex chromosome development itself may involve sex-specific recombination rate (i.e., heterochiasmy), which is also poorly understood. The family Salmonidae is a model system for these phenomena, having undergone autotetraploidization and subsequent rediploidization in most of the genome at the base of the lineage. The salmonid master sex determining gene is known, and many species have nonhomologous sex chromosomes, putatively due to transposition of this gene. In this study, we identify the sex chromosome of Brook Charr Salvelinus fontinalis and compare sex chromosome identities across the lineage (eight species and four genera). Although nonhomology is frequent, homologous sex chromosomes and other consistencies are present in distantly related species, indicating probable convergence on specific sex and neo-sex chromosomes. We also characterize strong heterochiasmy with 2.7-fold more crossovers in maternal than paternal haplotypes with paternal crossovers biased to chromosome ends. When considering only rediploidized chromosomes, the overall heterochiasmy trend remains, although with only 1.9-fold more recombination in the female than the male. Y chromosome crossovers are restricted to a single end of the chromosome, and this chromosome contains a large interspecific inversion, although its status between males and females remains unknown. Finally, we identify quantitative trait loci (QTL) for 21 unique growth, reproductive, and stress-related phenotypes to improve knowledge of the genetic architecture of these traits important to aquaculture and evolution.

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RNA Binding Protein Vigilin Collaborates with miRNAs To Regulate Gene Expression for Caenorhabditis elegans Larval Development

Extensive studies have suggested that most miRNA functions are executed through complex miRNA-target interaction networks, and such networks function semiredundantly with other regulatory systems to shape gene expression dynamics for proper physiological functions. We found that knocking down vgln-1, which encodes a conserved RNA-binding protein associated with diverse functions, causes severe larval arrest at the early L1 stage in animals with compromised miRISC functions (an ain-2/GW182 mutant). Through an enhancer screen, we identified five specific miRNAs, and miRNA families, that act semiredundantly with VGLN-1 to regulate larval development. By RIP-Seq analysis, we identified mRNAs that are directly bound by VGLN-1, and highly enriched for miRNA binding sites, leading to a hypothesis that VGLN-1 may share common targets with miRNAs to regulate gene expression dynamics for development.

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Two Variants in SLC24A5 Are Associated with "Tiger-Eye" Iris Pigmentation in Puerto Rican Paso Fino Horses

A unique eye color, called tiger-eye, segregates in the Puerto Rican Paso Fino (PRPF) horse breed and is characterized by a bright yellow, amber, or orange iris. Pedigree analysis identified a simple autosomal recessive mode of inheritance for this trait. A genome-wide association study (GWAS) with 24 individuals identified a locus on ECA 1 reaching genome-wide significance (P_corrected = 1.32 x 10^–5). This ECA1 locus harbors the candidate gene, Solute Carrier Family 24 (Sodium/Potassium/Calcium Exchanger), Member 5 (SLC24A5), with known roles in pigmentation in humans, mice, and zebrafish. Humans with compound heterozygous mutations in SLC24A5 have oculocutaneous albinism (OCA) type 6 (OCA6), which is characterized by dilute skin, hair, and eye pigmentation, as well as ocular anomalies. Twenty tiger-eye horses were homozygous for a nonsynonymous mutation in exon 2 (p.Phe91Tyr) of SLC24A5 (called here Tiger-eye 1), which is predicted to be deleterious to protein function. Additionally, eight of the remaining 12 tiger-eye horses heterozygous for the p.Phe91Tyr variant were also heterozygous for a 628 bp deletion encompassing all of exon 7 of SLC24A5 (c.875-340_1081+82del), which we will call here the Tiger-eye 2 allele. None of the 122 brown-eyed horses were homozygous for either tiger-eye-associated allele or were compound heterozygotes. Further, neither variant was detected in 196 horses from four related breeds not known to have the tiger-eye phenotype. Here, we propose that two mutations in SLC24A5 affect iris pigmentation in tiger-eye PRPF horses. Further, unlike OCA6 in humans, the Tiger-eye 1 mutation in its homozygous state or as a compound heterozygote (Tiger-eye 1/Tiger-eye 2) does not appear to cause ocular anomalies or a change in coat color in the PRPF horse.

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Genetic Dissection of Morphometric Traits Reveals That Phytochrome B Affects Nucleus Size and Heterochromatin Organization in Arabidopsis thaliana

Microscopically visible chromatin is partitioned into two major components in Arabidopsis thaliana nuclei. On one hand, chromocenters are conspicuous foci of highly condensed "heterochromatic" domains that contain mostly repeated sequences. On the other hand, less condensed and gene-rich "euchromatin" emanates from these chromocenters. This differentiation, together with the dynamic nature of chromatin compaction in response to developmental and environmental stimuli, makes Arabidopsis a powerful system for studying chromatin organization and dynamics. Heterochromatin dynamics can be monitored by measuring the Heterochromatin Index, i.e., the proportion of nuclei displaying well-defined chromocenters, or the DNA fraction of chromocenters (relative heterochromatin fraction). Both measures are composite traits, thus their values represent the sum of effects of various underlying morphometric properties. We exploited genetic variation between natural occurring accessions to determine the genetic basis of individual nucleus and chromocenter morphometric parameters (area, perimeter, density, roundness, and heterogeneity) that together determine chromatin compaction. Our novel reductionist genetic approach revealed quantitative trait loci (QTL) for all measured traits. Genomic colocalization among QTL was limited, which suggests a complex genetic regulation of chromatin compaction. Yet genomic intervals of QTL for nucleus size (area and perimeter) both overlap with a known QTL for heterochromatin compaction that is explained by natural polymorphism in the red/far-red light and temperature receptor Phytochrome B. Mutant analyses and genetic complementation assays show that Phytochrome B is a negative regulator of nucleus size, revealing that perception of climatic conditions by a Phytochrome-mediated hub is a major determinant for coordinating nucleus size and heterochromatin compaction.

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Transcriptional Profiling of Biofilm Regulators Identified by an Overexpression Screen in Saccharomyces cerevisiae

Biofilm formation by microorganisms is a major cause of recurring infections and removal of biofilms has proven to be extremely difficult given their inherent drug resistance . Understanding the biological processes that underlie biofilm formation is thus extremely important and could lead to the development of more effective drug therapies, resulting in better infection outcomes. Using the yeast Saccharomyces cerevisiae as a biofilm model, overexpression screens identified DIG1, SFL1, HEK2, TOS8, SAN1, and ROF1/YHR177W as regulators of biofilm formation. Subsequent RNA-seq analysis of biofilm and nonbiofilm-forming strains revealed that all of the overexpression strains, other than DIG1 and TOS8, were adopting a single differential expression profile, although induced to varying degrees. TOS8 adopted a separate profile, while the expression profile of DIG1 reflected the common pattern seen in most of the strains, plus substantial DIG1-specific expression changes. We interpret the existence of the common transcriptional pattern seen across multiple, unrelated overexpression strains as reflecting a transcriptional state, that the yeast cell can access through regulatory signaling mechanisms, allowing an adaptive morphological change between biofilm-forming and nonbiofilm states.

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Constraints on eQTL Fine Mapping in the Presence of Multisite Local Regulation of Gene Expression

Expression quantitative trait locus (eQTL) detection has emerged as an important tool for unraveling of the relationship between genetic risk factors and disease or clinical phenotypes. Most studies use single marker linear regression to discover primary signals, followed by sequential conditional modeling to detect secondary genetic variants affecting gene expression. However, this approach assumes that functional variants are sparsely distributed and that close linkage between them has little impact on estimation of their precise location and the magnitude of effects. We describe a series of simulation studies designed to evaluate the impact of linkage disequilibrium (LD) on the fine mapping of causal variants with typical eQTL effect sizes. In the presence of multisite regulation, even though between 80 and 90% of modeled eSNPs associate with normally distributed traits, up to 10% of all secondary signals could be statistical artifacts, and at least 5% but up to one-quarter of credible intervals of SNPs within r² > 0.8 of the peak may not even include a causal site. The Bayesian methods eCAVIAR and DAP (Deterministic Approximation of Posteriors) provide only modest improvement in resolution. Given the strong empirical evidence that gene expression is commonly regulated by more than one variant, we conclude that the fine mapping of causal variants needs to be adjusted for multisite influences, as conditional estimates can be highly biased by interference among linked sites, but ultimately experimental verification of individual effects is needed. Presumably similar conclusions apply not just to eQTL mapping, but to multisite influences on fine mapping of most types of quantitative trait.

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Excellance, Inc. finishes CNG unit for fire department

The compressed natural gas unit burns cleaner and lowers fuel costs

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The contexts and early Acheulean archaeology of the EF-HR paleo-landscape (Olduvai Gorge, Tanzania)

Publication date: Available online 7 August 2017
Source:Journal of Human Evolution
Author(s): Ignacio de la Torre, Rosa M. Albert, Richard Macphail, Lindsay J. McHenry, Michael C. Pante, Ágata Rodríguez-Cintas, Ian G. Stanistreet, Harald Stollhofen
Renewed fieldwork at the early Acheulean site of EF-HR (Olduvai Gorge, Tanzania) has included detailed stratigraphic studies of the sequence, extended excavations in the main site, and has placed eleven additional trenches within an area of nearly 1 km², to sample the same stratigraphic interval as in the main trench across the broader paleo-landscape. Our new stratigraphic work suggests that EF-HR is positioned higher in the Bed II sequence than previously proposed, which has implications for the age of the site and its stratigraphic correlation to other Olduvai Middle Bed II sites. Geological research shows that the main EF-HR site was situated at the deepest part of an incised valley formed through river erosion. Archaeological excavations at the main site and nearby trenches have unearthed a large new assemblage, with more than 3000 fossils and artefacts, including a hundred handaxes in stratigraphic position. In addition, our test-trenching approach has detected conspicuous differences in the density of artefacts across the landscape, with a large cluster of archaeological material in and around the main trench, and less intense human activity at the same level in the more distant satellite trenches. All of these aspects are discussed in this paper in the light of site formation processes, behavioral contexts, and their implications for our understanding of the early Acheulean at Olduvai Gorge.



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Journal Club.

No abstract available

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Brain Monitoring and the Depth of Anesthesia: Another Goldilocks Dilemma.

No abstract available

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Perioperative Acute Kidney Injury: An Under-recognized Problem.

The incidence of perioperative acute kidney injury (AKI) is more common than previously recognized, especially in high-risk patients undergoing higher risk procedures. The growing number of patients who develop perioperative AKI is related, in part, to the aging population and increase in the number of individuals with chronic comorbidities, particularly those with premorbid chronic kidney disease. Despite the acceptance of standardization in the definition of AKI, clinicians routinely underdiagnose it and fail to appreciate that it is associated with considerable morbidity and mortality. Unfortunately, few, if any, preemptive therapies have proven effective in preventing AKI. Timely diagnostic methods using evolving biomarkers raises the prospect of detection of kidney damage before the onset of irreversible loss of function, but remain under investigation. Clear evidence supporting any therapeutic intervention except renal replacement therapy remains elusive. Renal replacement therapy is indicated for select patients with progressive AKI; however, the ideal timing, method, and application of it remain under debate. It is fundamental to identify patients at risk for AKI. The Kidney Disease: Improving Global Outcomes guidelines suggest preventive strategies that include avoidance of nephrotoxic agents and hyperglycemia, optimization of hemodynamics, restoration of the circulating volume, and institution of functional hemodynamic monitoring. Clear evidence in support of this approach, however, is lacking. Recently, the perioperative administration of dexmedetomidine and the provision of remote ischemic preconditioning have been studied to potentially limit the development of perioperative AKI. This review discusses accepted standard definitions of AKI, highlights associated risk factors for its development, and provides an overview of its epidemiology and pathology. It emphasizes potential preventive strategies, the possible role of emerging biomarkers in defining its presence more expeditiously before irreversible injury, and current recommended guidelines and therapeutic approaches. The ultimate goal of this article is to bring to the attention of clinicians the seriousness of this potentially preventable or modifiable perioperative complication. (C) 2017 International Anesthesia Research Society

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Optimization of Endotracheal Tube Cuff Pressure by Monitoring CO2 Levels in the Subglottic Space in Mechanically Ventilated Patients: A Randomized Controlled Trial.

BACKGROUND: Many of the complications of mechanical ventilation are related to inappropriate endotracheal tube (ETT) cuff pressure. The aim of the current study was to evaluate the effectiveness of automatic cuff pressure closed-loop control in patients under prolonged intubation, where presence of carbon dioxide (CO2) in the subglottic space is used as an indicator for leaks. The primary outcome of the study is leakage around the cuff quantified using the area under the curve (AUC) of CO2 leakage over time. METHODS: This was a multicenter, prospective, randomized controlled, noninferiority trial including intensive care unit patients. All patients were intubated with the AnapnoGuard ETT, which has an extra lumen used to monitor CO2 levels in the subglottic space. The study group was connected to the AnapnoGuard system operating with cuff control adjusted automatically based on subglottic CO2 (automatic group). The control group was connected to the AnapnoGuard system, while cuff pressure was managed manually using a manometer 3 times/d (manual group). The system recorded around cuff CO2 leakage in both groups. RESULTS: Seventy-two patients were recruited and 64 included in the final analysis. The mean hourly around cuff CO2 leak (mm Hg AUC/h) was 0.22 +/- 0.32 in the manual group and 0.09 +/- 0.04 in the automatic group (P = .01) where the lower bound of the 1-sided 95% confidence interval was 0.05, demonstrating noninferiority (>-0.033). Additionally, the 2-sided 95% confidence interval was 0.010 to 0.196, showing superiority (>0.0) as well. Significant CO2 leakage (CO2 >2 mm Hg) was 0.027 +/- 0.057 (mm Hg AUC/h) in the automatic group versus 0.296 +/- 0.784 (mm Hg AUC/h) in the manual group (P = .025). In addition, cuff pressures were in the predefined safety range 97.6% of the time in the automatic group compared to 48.2% in the automatic group (P

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Fundamentals of Research Data and Variables: The Devil Is in the Details.

Designing, conducting, analyzing, reporting, and interpreting the findings of a research study require an understanding of the types and characteristics of data and variables. Descriptive statistics are typically used simply to calculate, describe, and summarize the collected research data in a logical, meaningful, and efficient way. Inferential statistics allow researchers to make a valid estimate of the association between an intervention and the treatment effect in a specific population, based upon their randomly collected, representative sample data. Categorical data can be either dichotomous or polytomous. Dichotomous data have only 2 categories, and thus are considered binary. Polytomous data have more than 2 categories. Unlike dichotomous and polytomous data, ordinal data are rank ordered, typically based on a numerical scale that is comprised of a small set of discrete classes or integers. Continuous data are measured on a continuum and can have any numeric value over this continuous range. Continuous data can be meaningfully divided into smaller and smaller or finer and finer increments, depending upon the precision of the measurement instrument. Interval data are a form of continuous data in which equal intervals represent equal differences in the property being measured. Ratio data are another form of continuous data, which have the same properties as interval data, plus a true definition of an absolute zero point, and the ratios of the values on the measurement scale make sense. The normal (Gaussian) distribution ("bell-shaped curve") is of the most common statistical distributions. Many applied inferential statistical tests are predicated on the assumption that the analyzed data follow a normal distribution. The histogram and the Q-Q plot are 2 graphical methods to assess if a set of data have a normal distribution (display "normality"). The Shapiro-Wilk test and the Kolmogorov-Smirnov test are 2 well-known and historically widely applied quantitative methods to assess for data normality. Parametric statistical tests make certain assumptions about the characteristics and/or parameters of the underlying population distribution upon which the test is based, whereas nonparametric tests make fewer or less rigorous assumptions. If the normality test concludes that the study data deviate significantly from a Gaussian distribution, rather than applying a less robust nonparametric test, the problem can potentially be remedied by judiciously and openly: (1) performing a data transformation of all the data values; or (2) eliminating any obvious data outlier(s). (C) 2017 International Anesthesia Research Society

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The Placement of Syringe Labels May Reduce Medication Errors and Cognitive Load.

No abstract available

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Microparticle Release During Normal Cesarean Delivery.

Coagulation increases during pregnancy and peaks during parturition. We hypothesized that an increase in microparticle (MP) levels in plasma occurs around the time of placental separation and subsides over several hours. We performed a prospective observational pilot study to investigate plasma MP levels in healthy parturients immediately before and after cesarean delivery. The primary outcome was MP levels at postdelivery time points compared to baseline levels. Samples underwent flow cytometry and staining to determine MP levels. Placental-derived MPs were further characterized for the presence of procoagulant proteins. Placental-derived MPs increased immediately after delivery before returning to baseline in healthy parturients. (C) 2017 International Anesthesia Research Society

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In Response.

No abstract available

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Repeated Administration of Amitriptyline in Neuropathic Pain: Modulation of the Noradrenergic Descending Inhibitory System.

BACKGROUND: The tricyclic antidepressant amitriptyline, the serotonin and noradrenaline reuptake inhibitor duloxetine, and gabapentinoids are first-line drugs for treatment of neuropathic pain. The analgesic effect of these drugs relates to brainstem-spinal descending noradrenergic systems. However, amitriptyline utilizes a variety of mechanisms for analgesia in neuropathic pain, and it is unclear which mechanism is most important. In the present study, we investigated the role of descending noradrenergic systems in the analgesic effect of these drugs for treatment of neuropathic pain. We also examined whether amitriptyline modifies the descending noradrenergic systems. METHODS: Seven days after L5 spinal nerve ligation (SNL), rats received N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4, 50 mg/kg) to degenerate noradrenergic fibers. The rats then received 5 daily intraperitoneal injections of amitriptyline (10 mg/kg), duloxetine (10 mg/kg), pregabalin (10 mg/kg), or gabapentin (50 mg/kg) from 21 days after SNL surgery. Paw withdrawal thresholds were determined to assess the effect of the drugs on hyperalgesia after SNL. To determine whether 5 daily injections of amitriptyline activated noradrenergic neurons in the locus coeruleus (LC) and spinal cord with or without DSP-4 treatment, we performed immunohistochemistry using antibodies for c-Fos and dopamine beta-hydroxylase (D[beta]H). RESULTS: Five daily injections of amitriptyline, duloxetine, pregabalin, and gabapentin exerted antihyperalgesic effects in SNL rats (P

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Antiallodynic Effects of Endomorphin-1 and Endomorphin-2 in the Spared Nerve Injury Model of Neuropathic Pain in Mice.

BACKGROUND: The spared nerve injury (SNI) model is a new animal model that can mimic several characteristics of clinical neuropathic pain. Opioids are recommended as treatment of neuropathic pain. Therefore, the present study was conducted to investigate the antinociceptive effects of endomorphin-1 (EM-1) and endomorphin-2 (EM-2) given centrally and peripherally in the SNI model of neuropathic pain in mice. METHODS: The SNI model was made in mice by sparing the sural nerve intact, when the other 2 of 3 terminal branches of the sciatic nerve (common peroneal and tibial nerves) were tightly ligated and cut. Von Frey monofilaments were used to measure the SNI-induced mechanical allodynia-like behavior. The antiallodynic effects of EM-1 and EM-2 were determined after central and peripheral administration in the SNI model of neuropathic pain. Also, the specific opioid receptor antagonists were used to determine the opioid mechanisms of EMs involved in neuropathic pain. Values were expressed as the mean +/- standard deviation. RESULTS: Our results showed that the SNI mice developed prolonged mechanical allodynia-like behavior in ipsilateral paw after surgery, with the withdrawal threshold value being 0.061 +/- 0.02 g after 14 days. EM-1 and EM-2 produced significant antiallodynic effects in ipsilateral paw after intracerebroventricular (i.c.v.) administration, more effective than that of morphine. The peak withdrawal thresholds of 10 nmol EM-1 and EM-2 determined at 5 minutes after injection were 0.92 +/- 0.36 and 0.87 +/- 0.33 g, respectively, higher than that of morphine (0.46 +/- 0.20 g). Moreover, both EMs (10 nmol, i.c.v.) exerted significant antiallodynic effects in the contralateral paw, whereas no significant antinociceptive activity was seen after i.c.v. administration of morphine with equimolar dose. It was noteworthy that EM-1 and EM-2 produced antinociception through distinct [mu]1- and [mu]2-opioid receptor subtypes, and the EM-2-induced antiallodynia contained an additional component that was mediated by the release of endogenous dynorphin A, acting on [kappa]-opioid receptor. In addition, the antiallodynic activities of peripheral administration of EM-1, EM-2, and morphine were also investigated. Intraplantar, but not subcutaneous administration of EM-1 and EM-2 also exhibited potent antinociception, establishing the peripheral and local effects. Both [mu]1- and [mu]2-opioid receptor subtypes, but not the [delta]- or [kappa]-opioid receptors were involved in the peripheral antiallodynia of EMs. CONCLUSIONS: The present investigation demonstrated that both EM-1 and EM-2 given centrally and peripherally produced potent antiallodynic activities in SNI mice, and differential opioid mechanisms were involved. (C) 2017 International Anesthesia Research Society

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Repeated Administration of Duloxetine Suppresses Neuropathic Pain by Accumulating Effects of Noradrenaline in the Spinal Cord.

BACKGROUND: Antidepressants are used to treat neuropathic pain and although the detailed mechanisms of their effects are unclear, the descending noradrenergic inhibitory system might play an important role. We tested our hypothesis that repeated administration of duloxetine suppresses neuropathic pain by restoring the descending noradrenergic inhibitory system in rats 6 weeks after spinal nerve ligation (SNL). METHODS: We subcutaneously injected SNL rats with duloxetine (10 mg kg-1 day-1) daily for 3 consecutive days and assessed behavioral hypersensitivity and noxious stimulus-induced analgesia (NSIA) activated by subcutaneous injection of capsaicin. We also performed microdialysis studies of the spinal cord, noradrenaline measurements of homogenized lumbar spinal tissue, and immunohistochemistry of the locus coeruleus. RESULTS: Three daily injections of duloxetine attenuated the mechanical hyperalgesia induced by SNL (SNL treated with vehicle: 88 +/- 9.4 g versus SNL treated with duloxetine: 148 +/- 13 g, P

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Simple and inexpensive technique for measuring oxygen consumption rate in adherent cultured cells

Abstract

Measurement of cellular oxygen consumption rate (OCR) is essential in assessing roles of mitochondria in physiology and pathophysiology. Classical techniques, in which polarographic oxygen electrode measures the extracellular oxygen concentration in a closed measuring vessel, require isolation and suspension of the cell. Because cell functions depend on the extracellular milieu including the extracellular matrix, isolation of cultured cells prior to the measurement may significantly affect the OCR. More recent techniques utilize optical methods in which oxygen-dependent quenching of fluorophores determines oxygen concentration in the medium at a few microns above the surface of the cultured cells. These techniques allow the OCR measurement in cultured cells adhered to the culture dish. However, this technique requires special equipment such as a fluorescence lifetime microplate reader or specialized integrated system, which are usually quite expensive. Here, we introduce a simple and inexpensive technique for measuring OCR in adherent cultured cells that utilizes conventional fluorescence microscopy and a glassware called a gap cover glass.

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Firehouse Subs gives grant to Idaho paramedics for ballistic vests

The vests will help ensure "TacMed" is safe when entering hostile environments to provide care to police officers, innocent victims, bystanders and suspects

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EMS - Sales - Intersurgical Inc.

Responsibilities: " Continuously develop product knowledge, stay up to date with the industry changes within the EMS market. " Implement sales plan and achieve sales goals and objectives set for the geographic territory. " Maintain existing customers and prospect and gain new business. " Facilitate sales growth by conducting medical director, administrator and all levels of pre-hospital care provider ...

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EMT/AEMT/Paramedic - Eagle River, WI - Spirit Medical Transportation

EMT OR AEMT OR Paramedic - 911 / Eagle River, WI / FT Rotating Shifts / 72 Hours Biweekly in Eagle River, Wisconsin Additional Job Information Spirit Medical Transportation has an opening for an EMT-B, AEMT, or Paramedic. Please see link for full job description and application: http://ift.tt/2vIhQje City, State: ...

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Controlling 212Bi to 212Pb activity concentration ratio in thoron chambers

Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Zhengzhong He, Detao Xiao, Lidan Lv, Qingzhi Zhou, Jian Shan, Shoukang Qiu, Xijun Wu
It is necessary to establish a reference atmosphere in a thoron chamber containing various ratios of ²¹²Bi to ²¹²Pb activity concentrations (C(²¹²Bi)/C(²¹²Pb)) to simulate typical environmental conditions (e.g., indoor or underground atmospheres). In this study, a novel method was developed for establishing and controlling C(²¹²Bi)/C(²¹²Pb) in a thoron chamber system based on an aging chamber and air recirculation loops which alter the ventilation rate. The effects of main factors on the C(²¹²Bi)/C(²¹²Pb) were explored, and a steady-state theoretical model was derived to calculate the ratio. The results show that the C(²¹²Bi)/C(²¹²Pb) inside the chamber is mainly dependent on ventilation rate. Ratios ranging from 0.33 to 0.83 are available under various ventilation. The stability coefficient of the ratios is better than 7%. The experimental results are close to the theoretical calculated results, which indicates that the model can serve as a guideline for the quantitative control of C(²¹²Bi)/C(²¹²Pb).



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Low 134Cs/137Cs ratio anomaly in the north-northwest direction from the Fukushima Dai-ichi Nuclear Power Station

Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Shingo Kobayashi, Takayuki Shinomiya, Takahiro Ishikawa, Hitoshi Imaseki, Kazuki Iwaoka, Hisashi Kitamura, Satoshi Kodaira, Keisuke Kobayashi, Masakazu Oikawa, Norihiro Miyaushiro, Yoshio Takashima, Yukio Uchihori
A low ¹³⁴Cs/¹³⁷Cs ratio anomaly in the north-northwest (NNW) direction from the Fukushima Dai-ichi Nuclear Power Station (FDNPS) is identified by a new analysis of the ¹³⁴Cs/¹³⁷Cs ratio dataset which we had obtained in 2011–2015 by a series of car-borne surveys that employed a germanium gamma-ray spectrometer. We found that the ¹³⁴Cs/¹³⁷Cs ratio is slightly lower (0.95, decay-corrected to March 11, 2011) in an area with a length of about 15 km and a width of about 3 km in the NNW direction from the FDNPS than in other directions from the station. Furthermore, the area of this lower ¹³⁴Cs/¹³⁷Cs ratio anomaly corresponds to a narrow contamination band that runs NNW from the FDNPS and it is nearly parallel with the major and heaviest contamination band in the west-northwest. The plume trace with a low ¹³⁴Cs/¹³⁷Cs ratio previously found by other researchers within the 3-km radius of the FDNPS is in a part of the area with the lower ¹³⁴Cs/¹³⁷Cs ratio anomaly that we found. Our result suggests that this lower ¹³⁴Cs/¹³⁷Cs ratio anomaly is the area which was contaminated before March 13, 2011 (UTC) in association with the hydrogen explosion of Unit 1 on March 12, 2011 at 06:36 (UTC) and it was less influenced by later subsequent plumes.



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Ambulance, minivan collide head-on at busy intersection

The driver of the minivan was seriously injured; two paramedics were taken to a hospital

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18-year-old EMT falls asleep at the wheel, crashes ambulance

This is the third incident in Maine of an EMS provider falling asleep at the wheel in the last 30 days

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Adaptation modulates correlated subthreshold response variability in visual cortex

Cortical sensory responses are highly variable across stimulus presentations. This variability can be correlated across neurons (due to some combination of dense intracortical connectivity, cortical activity level, and cortical state), with fundamental implications for population coding. Yet the interpretation of correlated response variability (or "noise correlation") has remained fraught with difficulty, in part because of the restriction to extracellular neuronal spike recordings. Here, we measured response variability and its correlation at the most microscopic level of electrical neural activity, the membrane potential, by obtaining dual whole cell recordings from pairs of cortical pyramidal neurons during visual processing in the turtle whole brain ex vivo preparation. We found that during visual stimulation, correlated variability adapts toward an intermediate level and that this correlation dynamic is likely mediated by intracortical mechanisms. A model network with external inputs, synaptic depression, and structure reproduced the observed dynamics of correlated variability. These results suggest that intracortical adaptation self-organizes cortical circuits toward a balanced regime at which correlated variability is maintained at an intermediate level.

NEW & NOTEWORTHY Correlated response variability has profound implications for stimulus encoding, yet our understanding of this phenomenon is based largely on spike data. Here, we investigate the dynamics and mechanisms of membrane potential-correlated variability (CC) in visual cortex with a combined experimental and computational approach. We observe a visually evoked increase in CC, followed by a fast return to baseline. Our results further suggest a link between this observation and the adaptation-mediated dynamics of emergent network phenomena.

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Supramodal representation of temporal priors calibrates interval timing

Human timing behaviors are consistent with Bayesian inference, according to which both previous knowledge (prior) and current sensory information determine final responses. However, it is unclear whether the brain represents temporal priors exclusively for individual modalities or in a supramodal manner when temporal information comes from different modalities at different times. Here we asked participants to reproduce time intervals in either a unisensory or a multisensory context. In unisensory tasks, sample intervals drawn from a uniform distribution were presented in a single visual or auditory modality. In multisensory tasks, sample intervals from the two modalities were randomly mixed; visual and auditory intervals were drawn from two adjacent uniform distributions, with the conjunction of the two being equal to the distribution in the unisensory tasks. In the unisensory tasks, participants' reproduced times exhibited classic central-tendency biases: shorter intervals were overestimated and longer intervals were underestimated. In the multisensory tasks, reproduced times were biased toward the mean of the whole distribution rather than the means of intervals in individual modalities. The Bayesian model with a supramodal prior (distribution of time intervals from both modalities) outperformed the model with modality-specific priors in describing participants' performance. With a generalized model assuming the weighted combination of unimodal priors, we further obtained the relative contribution of visual intervals and auditory intervals in forming the prior for each participant. These findings suggest a supramodal mechanism for encoding priors in temporal processing, although the extent of influence of one modality on another differs individually.

NEW & NOTEWORTHY Visual timing and auditory timing influence each other when time intervals in the two modalities are drawn from two adjacent distributions and are randomly intermixed. A Bayesian model with a supramodal prior (distribution of intervals from both modalities) outperforms the model using sensory-specific priors in describing participants' performance. A generalized model further reveals that the prior is represented as a weighted average of the distribution of time intervals from the two modalities, which differ individually.

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Functional connectivity between somatosensory and motor brain areas predicts individual differences in motor learning by observing

Action observation can facilitate the acquisition of novel motor skills; however, there is considerable individual variability in the extent to which observation promotes motor learning. Here we tested the hypothesis that individual differences in brain function or structure can predict subsequent observation-related gains in motor learning. Subjects underwent an anatomical MRI scan and resting-state fMRI scans to assess preobservation gray matter volume and preobservation resting-state functional connectivity (FC), respectively. On the following day, subjects observed a video of a tutor adapting her reaches to a novel force field. After observation, subjects performed reaches in a force field as a behavioral assessment of gains in motor learning resulting from observation. We found that individual differences in resting-state FC, but not gray matter volume, predicted postobservation gains in motor learning. Preobservation resting-state FC between left primary somatosensory cortex and bilateral dorsal premotor cortex, primary motor cortex, and primary somatosensory cortex and left superior parietal lobule was positively correlated with behavioral measures of postobservation motor learning. Sensory-motor resting-state FC can thus predict the extent to which observation will promote subsequent motor learning.

NEW & NOTEWORTHY We show that individual differences in preobservation brain function can predict subsequent observation-related gains in motor learning. Preobservation resting-state functional connectivity within a sensory-motor network may be used as a biomarker for the extent to which observation promotes motor learning. This kind of information may be useful if observation is to be used as a way to boost neuroplasticity and sensory-motor recovery for patients undergoing rehabilitation for diseases that impair movement such as stroke.

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Spinal control of motor outputs by intrinsic and externally induced electric field potentials

Despite numerous studies on spinal neuronal systems, several issues regarding their role in motor behavior remain unresolved. One of these issues is how electric fields associated with the activity of spinal neurons influence the operation of spinal neuronal networks and how effects of these field potentials are combined with other means of modulating neuronal activity. Another closely related issue is how external electric field potentials affect spinal neurons and how they can be used for therapeutic purposes such as pain relief or recovery of motor functions by transspinal direct current stimulation. Nevertheless, progress in our understanding of the spinal effects of electric fields and their mechanisms has been made over the last years, and the aim of the present review is to summarize the recent findings in this field.

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Long-lasting increase in axonal excitability after epidurally applied DC

Effects of direct current (DC) on nerve fibers have primarily been investigated during or just after DC application. However, locally applied cathodal DC was recently demonstrated to increase the excitability of intraspinal preterminal axonal branches for >1 h. The aim of this study was therefore to investigate whether DC evokes a similarly long-lasting increase in the excitability of myelinated axons within the dorsal columns. The excitability of dorsal column fibers stimulated epidurally was monitored by recording compound action potentials in peripheral nerves in acute experiments in deeply anesthetized rats. The results show that 1) cathodal polarization (0.8–1.0 µA) results in a severalfold increase in the number of epidurally activated fibers and 2) the increase in the excitability appears within seconds, 3) lasts for >1 h, and 4) is activity independent, as it does not require fiber stimulation during the polarization. These features demonstrate an unexplored form of plasticity of myelinated fibers and indicate the conditions under which it develops. They also suggest that therapeutic effects of epidural stimulation may be significantly enhanced if it is combined with DC polarization. In particular, by using DC to increase the number of fibers activated by low-intensity epidural stimuli, the low clinical tolerance to higher stimulus intensities might be overcome. The activity independence of long-lasting DC effects would also allow the use of only brief periods of DC polarization preceding epidural stimulation to increase the effect.

NEW & NOTEWORTHY The study indicates a new form of plasticity of myelinated fibers. The differences in time course of DC-evoked increases in the excitability of myelinated nerve fibers in the dorsal columns and in preterminal axonal branches suggest that distinct mechanisms are involved in them. The results show that combining epidural stimulation and transspinal DC polarization may dramatically improve their outcome and result in more effective pain control and the return of impaired motor functions.

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Fetal alcohol exposure reduces responsiveness of taste nerves and trigeminal chemosensory neurons to ethanol and its flavor components

Fetal alcohol exposure (FAE) leads to increased intake of ethanol in adolescent rats and humans. We asked whether these behavioral changes may be mediated in part by changes in responsiveness of the peripheral taste and oral trigeminal systems. We exposed the experimental rats to ethanol in utero by administering ethanol to dams through a liquid diet; we exposed the control rats to an isocaloric and isonutritive liquid diet. To assess taste responsiveness, we recorded responses of the chorda tympani (CT) and glossopharyngeal (GL) nerves to lingual stimulation with ethanol, quinine, sucrose, and NaCl. To assess trigeminal responsiveness, we measured changes in calcium levels of isolated trigeminal ganglion (TG) neurons during stimulation with ethanol, capsaicin, mustard oil, and KCl. Compared with adolescent control rats, the adolescent experimental rats exhibited diminished CT nerve responses to ethanol, quinine, and sucrose and GL nerve responses to quinine and sucrose. The reductions in taste responsiveness persisted into adulthood for quinine but not for any of the other stimuli. Adolescent experimental rats also exhibited reduced TG neuron responses to ethanol, capsaicin, and mustard oil. The lack of change in responsiveness of the taste nerves to NaCl and the TG neurons to KCl indicates that FAE altered only a subset of the response pathways within each chemosensory system. We propose that FAE reprograms development of the peripheral taste and trigeminal systems in ways that reduce their responsiveness to ethanol and surrogates for its pleasant (i.e., sweet) and unpleasant (i.e., bitterness, oral burning) flavor attributes.

NEW & NOTEWORTHY Pregnant mothers are advised to avoid alcohol. This is because even small amounts of alcohol can alter fetal brain development and increase the risk of adolescent alcohol abuse. We asked how fetal alcohol exposure (FAE) produces the latter effect in adolescent rats by measuring responsiveness of taste nerves and trigeminal chemosensory neurons. We found that FAE substantially reduced taste and trigeminal responsiveness to ethanol and its flavor components.

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Successful endoscopic submucosal dissection of colon cancer with severe fibrosis after tattooing

Abstract

Endoscopic tattooing is often used to facilitate the identification of colorectal lesions before endoscopic treatments. However, tattooing under the lesion can result in technical difficulties because of the dark endoscopic field and submucosal fibrosis. A 65-year-old man with a non-granular-type laterally spreading tumor was referred to our hospital after tattooing with India ink for surgery. However, endoscopic submucosal dissection (ESD) was selected for the resection of this lesion because the findings of magnifying endoscopy suggested an intramucosal cancer. Dissection around a dense section was difficult because of the dark endoscopic field and non-lifting as a result of severe fibrosis. We performed ESD using the following strategy: (1) injection with a smaller amount of indigo carmine and (2) cut and dissection from the side of the thinly tattooed area. The lesion was curatively resected en bloc without any complications. This finding suggests that endoscopic tattooing before endoscopic treatment should be performed one or two folds away from the lesion.

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3 ways to avoid injuries when lifting patients

Exercise, use powered patient transport equipment and keep moving to reduce the likelihood of on-the-job injury

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2017 EMS Trend Report: The forces shaping the future of EMS

EMS1 and Fitch & Associates take an in-depth look at EMS trends in the United States and set a foundation for assessing how the EMS profession is changing

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Changing relative crank angle increases the metabolic cost of leg cycling

Abstract

Purpose

Historically, the efficiency of leg cycling has been difficult to change. However, arm cycling research indicates that relative crank angle changes can improve efficiency. Therefore, we investigated if leg cycling with different relative crank angles affects efficiency.

Methods

Ten healthy, male, recreational bicycle riders (27.8 ± 8.2 years, mean ± SD, mass 69.8 ± 3.2 kg) pedaled a pan-loaded cycle ergometer at a fixed power output of 150 watts at a cadence of 90 RPM. Each subject completed six, 5-min trials in random order at relative crank angles of 180°, 135°, 90°, 45°, 0°, and 180°. We averaged rates of oxygen uptake ( \({\dot{\text{V}}\text{O}}_{ 2}\) ) and carbon dioxide production ( \({\dot{\text{V}}\text{CO}}_{ 2}\) ), and respiratory exchange ratio (RER) for the last 2 min of each trial.

Results

Crank angles other than 180° required a greater metabolic cost. As relative crank angle decreased from 180°, metabolic power monotonically increased by 1.6% at 135° to 8.2% greater when the relative crank angle was 0° (p < 0.001).

Conclusions

We find that, unlike arm cycling, radically changing the relative crank angle on a bicycle from an out-of-phase (180°) to in-phase (0°) position decreases leg cycling efficiency by ~8%. We attribute the increase to changes in cost of breathing, muscle co-activation, trunk stabilization, power fluctuations, and possibly lifting the legs during the upstroke. Our findings may have relevance in the rehabilitation of patients recovering from stroke or spinal cord injury.

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Detection of phasic dopamine by D1 and D2 striatal medium spiny neurons

Abstract

The phasic release of dopamine in the striatum determines various aspects of reward and action selection, but the dynamics of dopamine effect on intracellular signalling remains poorly understood. We used genetically-encoded FRET biosensors in striatal brain slices to quantify the effect of transient dopamine on cAMP or PKA-dependent phosphorylation level, and computational modelling to further explore the dynamics of this signalling pathway. Medium-sized spiny neurons (MSNs), which express either D1 or D2 dopamine receptors, responded to dopamine by an increase or a decrease in cAMP, respectively. Transient dopamine showed similar sub-micromolar efficacies on cAMP in both D1 and D2 MSNs, thus challenging the commonly accepted notion that dopamine efficacy is much higher on D2 than on D1 receptors. However, in D2 MSNs, the large decrease in cAMP level triggered by transient dopamine did not translate in a decrease in PKA-dependent phosphorylation level, owing to the efficient inhibition of Protein Phosphatase 1 by DARPP-32. Simulations further suggested that D2 MSNs can also operate in a "tone-sensing" mode, allowing them to detect transient dips in basal dopamine. Overall, our results show that D2 MSNs may sense much more complex patterns of dopamine than previously thought.

This article is protected by copyright. All rights reserved

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Effect on Helicobacter pylori eradication therapy against gastric cancer in Japan

Helicobacter

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Early, frequent cannabis use tied to depression, suicidal thoughts

Reuters Health News

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Laparoscopic resection for gastrointestinal stromal tumors in esophagogastric junction (EGJ): How to protect the EGJ

Surgical Endoscopy

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Wal-Mart, Walgreens, CVS turn up the heat on generic drugmaker deals

Reuters Health News

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Development and validation of a prognostic model incorporating texture analysis derived from standardised segmentation of PET in patients with oesophageal cancer

European Radiology

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Shift in physician workforce towards specialists fuels primary care shortage, potential spending growth

Healthcare Finance News

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Health care disparities among octogenarians and nonagenarians with stage II and III rectal cancer

Cancer

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Dietary behaviors in relation to prevalence of irritable bowel syndrome in adolescent girls

Journal of Gastroenterology and Hepatology

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Clinical impact of small advanced gastric cancer (≤ 40 mm) in elderly patients: A retrospective cohort study

International Journal of Surgery

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Exclusive enteral nutrition for inducing remission in inflammatory bowel disease in paediatric patients

Current Opinion in Clinical Nutrition & Metabolic Care

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Prognostic significance of peritoneal lavage cytology in staging gastric cancer: Systematic review and meta-analysis

Gastric Cancer

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Therapeutic drug monitoring was helpful in guiding the decision-making process for children receiving infliximab for inflammatory bowel disease

Acta Pediatrica

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Short sleep linked to body mass, waist size

Reuters Health News

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The low FODMAP diet: Fundamental therapy in the management of irritable bowel syndrome

Current Opinion in Clinical Nutrition & Metabolic Care

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The prevalence of gastric heterotopia of the proximal esophagus is underestimated, but preneoplasia is rare - correlation with Barrett's esophagus

BMC Gastroenterology

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Identification of the anticancer effects of a novel proteasome inhibitor, ixazomib, on colorectal cancer using a combined method of microarray and bioinformatics analysis

OncoTargets and Therapy

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Elderly patients have similar short term outcomes and five-year survival compared to younger patients after pancreaticoduodenectomy

International Journal of Surgery

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Prognostic and predictive values of PD-L1 expression in patients with digestive system cancer: A meta-analysis

OncoTargets and Therapy

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Cell-free DNA in metastatic colorectal cancer: A systematic review and meta-analysis

The Oncologist

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Risk of acute myocardial infarction among hepatitis C virus (HCV)-positive and HCV-negative men at various lipid levels: Results from ERCHIVES

Clinical Infectious Diseases

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Epigenetics: Getting instructions from mum

Nature Reviews Genetics. doi:10.1038/nrg.2017.64

Author: Paulina Strzyz

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Complex disease: From non-coding risk variant to biological mechanism in CAD

Nature Reviews Genetics. doi:10.1038/nrg.2017.66

Author: Linda Koch

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