Gold nanoparticles improve metabolic profile of mice fed a high-fat diet

© 2018 The Author(s). Background: Obesity is a high risk for multiple metabolic disorders due to excessive influx of energy, glucose and lipid, often from a western based diet. Low-grade inflammation plays a key role in the progression of such metabolic disorders. The anti-inflammatory property of gold compounds has been used in treating rheumatoid arthritis in the clinic. Previously we found that pure gold nanoparticles (AuNPs, 21 nm) also possess anti-inflammatory effects on the retroperitoneal fat tissue following intraperitoneal injection, by downregulating tumor necrosis factor (TNF) α. However, whether such an effect can change the risk of metabolic disorders in the obese has not been well studied. The study employed C57BL/6 mice fed a pellet high fat diet (HFD, 43% as fat) that were treated daily with AuNPs [low (HFD-LAu) or high (HFD-HAu) dose] via intraperitoneal injection for 9 weeks. In the in vitro study, RAW264.7 macrophages and 3T3-L1 adipocytes were cultured with low and high concentrations of AuNPs alone or together. Results: The HFD-fed mice showed a significant increase in fat mass, glucose intolerance, dyslipidemia, and liver steatosis. The HFD-LAu group showed an 8% reduction in body weight, ameliorated hyperlipidemia, and normal glucose tolerance; while the HFD-HAu group had a 5% reduction in body weight with significant improvement in their glucose intolerance and hyperlipidemia. The underlying mechanism may be attributed to a reduction in adipose and hepatic local proinflammatory cytokine production, e.g. TNFα. In vitro studies of co-cultured murine RAW264.7 macrophage and 3T3-L1 adipocytes supported this proposed mechanism. Conclusion: AuNPs demonstrate a promising profile for potential management of obesity related glucose and lipid disorders and are useful as a research tool for the study of biological mechanisms

Are autistic traits in the general population stable across development?

There is accumulating evidence that autistic traits (AT) are on a continuum in the general population, with clinical autism representing the extreme end of a quantitative distribution. While the nature and severity of symptoms in clinical autism are known to persist over time, no study has examined the long-term stability of AT among typically developing toddlers. The current investigation measured AT in 360 males and 400 males from the general population close to two decades apart, using the Pervasive Developmental Disorder subscale of the Child Behavior Checklist in early childhood (M = 2.14 years; SD = 0.15), and the Autism-Spectrum Quotient in early adulthood (M = 19.50 years; SD = 0.70). Items from each scale were further divided into social (difficulties with social interaction and communication) and non-social (restricted and repetitive behaviours and interests) AT. The association between child and adult measurements of AT as well the influence of potentially confounding sociodemographic, antenatal and obstetric variables were assessed using Pearson's correlations and linear regression. For males, Total AT in early childhood were positively correlated with total AT (r = .16, p = .002) and social AT (r = .16, p = .002) in adulthood. There was also a positive correlation for males between social AT measured in early childhood and Total (r = .17, p = .001) and social AT (r = .16, p = .002) measured in adulthood. Correlations for non-social AT did not achieve significance in males. Furthermore, there was no significant longitudinal association in AT observed for males or females. Despite the constraints of using different measures and different raters at the two ages, this study found modest developmental stability of social AT from early childhood to adulthood in boys

Essential and checkpoint functions of budding yeast ATM and ATR during meiotic prophase are facilitated by differential phosphorylation of a meiotic adaptor protein, Hop1

A hallmark of the conserved ATM/ATR signalling is its ability to mediate a wide range of functions utilizing only a limited number of adaptors and effector kinases. During meiosis, Tel1 and Mec1, the budding yeast ATM and ATR, respectively, rely on a meiotic adaptor protein Hop1, a 53BP1/Rad9 functional analog, and its associated kinase Mek1, a CHK2/Rad53-paralog, to mediate multiple functions: control of the formation and repair of programmed meiotic DNA double strand breaks, enforcement of inter-homolog bias, regulation of meiotic progression, and implementation of checkpoint responses. Here, we present evidence that the multi-functionality of the Tel1/Mec1-to-Hop1/Mek1 signalling depends on stepwise activation of Mek1 that is mediated by Tel1/Mec1 phosphorylation of two specific residues within Hop1: phosphorylation at the threonine 318 (T318) ensures the transient basal level Mek1 activation required for viable spore formation during unperturbed meiosis. Phosphorylation at the serine 298 (S298) promotes stable Hop1-Mek1 interaction on chromosomes following the initial phospho-T318 mediated Mek1 recruitment. In the absence of Dmc1, the phospho-S298 also promotes Mek1 hyper-activation necessary for implementing meiotic checkpoint arrest. Taking these observations together, we propose that the Hop1 phospho-T318 and phospho-S298 constitute key components of the Tel1/Mec1- based meiotic recombination surveillance (MRS) network and facilitate effective coupling of meiotic recombination and progression during both unperturbed and challenged meiosis

Human Papillomavirus Risk Perceptions Among Young Adult Sexual Minority Cisgender Women and Nonbinary Individuals Assigned Female at Birth

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148405/1/psrh12087_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148405/2/psrh12087.pd

Reverse Engineering Gene Networks with ANN: Variability in Network Inference Algorithms

Motivation :Reconstructing the topology of a gene regulatory network is one of the key tasks in systems biology. Despite of the wide variety of proposed methods, very little work has been dedicated to the assessment of their stability properties. Here we present a methodical comparison of the performance of a novel method (RegnANN) for gene network inference based on multilayer perceptrons with three reference algorithms (ARACNE, CLR, KELLER), focussing our analysis on the prediction variability induced by both the network intrinsic structure and the available data. Results: The extensive evaluation on both synthetic data and a selection of gene modules of "Escherichia coli" indicates that all the algorithms suffer of instability and variability issues with regards to the reconstruction of the topology of the network. This instability makes objectively very hard the task of establishing which method performs best. Nevertheless, RegnANN shows MCC scores that compare very favorably with all the other inference methods tested. Availability: The software for the RegnANN inference algorithm is distributed under GPL3 and it is available at the corresponding author home page (http://mpba.fbk.eu/grimaldi/regnann-supmat

Which symptoms are linked to a delayed presentation among melanoma patients? A retrospective study

Background: The incidence of melanoma is rising. Early detection is associated with a more favourable outcome. The factors that influence the timing of a patient’s presentation for medical assessment are not fully understood. The aims of the study were to measure the nature and duration of melanoma symptoms in a group of patients diagnosed with melanoma within the preceding 18 months and to identify the symptoms and barriers associated with a delay in presentation. Methods: A questionnaire was distributed to a random sample of 200 of the 963 melanoma patients who had participated in the Cancer Patient Experience Survey 2010 and were known to be alive 1 year later. Data were collected on symptoms, duration of symptoms prior to presentation and the reasons for not attending a doctor sooner. Results: A total of 159 patients responded to the questionnaire; 74 (47%) were men; mean age was 62 (range 24–90) years. Of the 149 patients who reported a symptom, 40 (27%) had a delayed presentation (i.e. >3 months). A mole growing bigger was the most common symptom and reporting this symptom was significantly associated with a delayed presentation (odds ratio (OR) 2.04, 95% confidence interval (95% CI) 1.14–5.08). Patients aged ≥65 years were less likely to report a barrier to presentation and were less likely to delay than those under 40, although this was of borderline statistical significance (OR 0.28, 95% CI 0.08–1.00). Conclusions: This study highlights that an enlarging mole is a significant symptom influencing the timing of presentation. Increasing public awareness of the signs of melanoma and of the importance of early presentation is desirable. Health professionals should take advantage of the opportunity to educate patients on such symptoms and signs where feasible. Further exploration of the barriers to presentation in younger people should be considered

Rapid automatized naming as an index of genetic liability to autism

This study investigated rapid automatized naming (RAN) ability in high functioning individuals with autism and parents of individuals with autism. Findings revealed parallel patterns of performance in parents and individuals with autism, where both groups had longer naming times than controls. Significant parent-child correlations were also detected, along with associations with language and personality features of the broad autism phenotype (retrospective reports of early language delay, socially reticent personality). Together, findings point towards RAN as a potential marker of genetic liability to autism

Functional assays to determine the significance of two common XPC 3'UTR variants found in bladder cancer patients

<p>Abstract</p> <p>Background</p> <p><it>XPC </it>is involved in the nucleotide excision repair of DNA damaged by carcinogens known to cause bladder cancer. Individuals homozygous for the variant allele of <it>XPC </it>c.1496C > T (p.Ala499Val) were shown in a large pooled analysis to have an increased bladder cancer risk, and we found two 3'UTR variants, *611T > A and c.*618A > G, to be in strong linkage disequilibrium with c.1496T. Here we determined if these two 3'UTR variants can affect mRNA stability and assessed the impact of all three variants on mRNA and protein expression.</p> <p>Methods</p> <p><it>In vitro </it>mRNA stability assays were performed and mRNA and protein expression measured both in plasmid-based assays and in lymphocytes and lymphoblastoid cell lines from bladder and breast cancer patients.</p> <p>Results</p> <p>The two 3'UTR variants were associated with reduced protein and mRNA expression in plasmid-based assays, suggesting an effect on mRNA stability and/or transcription/translation. A near-significant reduction in XPC protein expression (p = 0.058) was detected in lymphoblastoid cell lines homozygous for these alleles but no differences in mRNA stability in these lines was found or in mRNA or protein levels in lymphocytes heterozygous for these alleles.</p> <p>Conclusion</p> <p>The two 3'UTR variants may be the variants underlying the association of c.1496C > T and bladder cancer risk acting via a mechanism modulating protein expression.</p

A Genome-Wide Analysis of Promoter-Mediated Phenotypic Noise in Escherichia coli

Gene expression is subject to random perturbations that lead to fluctuations in the rate of protein production. As a consequence, for any given protein, genetically identical organisms living in a constant environment will contain different amounts of that particular protein, resulting in different phenotypes. This phenomenon is known as “phenotypic noise.” In bacterial systems, previous studies have shown that, for specific genes, both transcriptional and translational processes affect phenotypic noise. Here, we focus on how the promoter regions of genes affect noise and ask whether levels of promoter-mediated noise are correlated with genes' functional attributes, using data for over 60% of all promoters in Escherichia coli. We find that essential genes and genes with a high degree of evolutionary conservation have promoters that confer low levels of noise. We also find that the level of noise cannot be attributed to the evolutionary time that different genes have spent in the genome of E. coli. In contrast to previous results in eukaryotes, we find no association between promoter-mediated noise and gene expression plasticity. These results are consistent with the hypothesis that, in bacteria, natural selection can act to reduce gene expression noise and that some of this noise is controlled through the sequence of the promoter region alon