Oh, You\u27re the one That\u27s Keeping Us Open: Senior Student Affairs officers\u27 Crisis Leadership and Decision Making in Response to COVID-19

The purpose of this dissertation was to understand the experience of higher education crisis leaders while facing an unprecedented crisis. COVID-19 thrust senior student affairs professionals, who most often serve as crisis leaders on small college campuses, into the position of decision-maker guiding the campus response to the pandemic. The research explored the crisis leadership experience of SSAOs during the first year of their crisis response. Five themes emerged from the data collected during the research: a) the influence of institutional structure and culture on decisions, b) uniqueness of crisis decision making, c) engagement and utilization of human resources, d) changes to professional practice/profile, and e) the emotional toll of crisis leadership. Implications for practice are offered as a result of the research conducted

Improved genetic testing for monogenic diabetes using targeted next-generation sequencing

addresses: Institute for Biomedical and Clinical Science, University of Exeter Medical School, Barrack Road, Exeter EX2 5DW, UK. [email protected]: PMCID: PMC3737433types: Journal Article; Research Support, Non-U.S. Gov'tOpen Access ArticleCurrent genetic tests for diagnosing monogenic diabetes rely on selection of the appropriate gene for analysis according to the patient's phenotype. Next-generation sequencing enables the simultaneous analysis of multiple genes in a single test. Our aim was to develop a targeted next-generation sequencing assay to detect mutations in all known MODY and neonatal diabetes genes

Thiamethoxam in Papaya (Carica papaya Linnaeus) Agroecosystems

Papaya (Carica papaya L.) is a profitable fruit of economic and food importance in Mexico and Central America. Veracruz is the state in Mexico with the highest cultivable area, eventhough its production presents numerous phytosanitary problems, which are being faced with the use of the pesticide thiamethoxam. The aim of this study was to make a diagnosis of the use and management of thiamethoxam in papaya agroecosystems in the municipality of Cotaxtla, Veracruz. Two surveys were applied, one to a 30% of the total number of producers organized by an association dedicated to papaya culture, and the other survey was through key informants, both surveys were designed using the snowball sampling, a non-probability sampling technique. The results indicate that 6% of papaya producers use mainly the pesticide thiamethoxam, which belongs to the chemical group of neonicotinoids. It was found out that for five years there have been records of thiamethoxam use in vertisoils. During the cycle of papaya cultivation the producers use a maximum dose of 3 L/ha and a minimum dose of 250 ml/ha per crop cycle. One hundred per cent of those who apply thiamethoxam are not aware of its use and efficient management, nor of the damage they are doing or have caused to agroecosystems

TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors.

The genomic regulatory programmes that underlie human organogenesis are poorly understood. Pancreas development, in particular, has pivotal implications for pancreatic regeneration, cancer and diabetes. We have now characterized the regulatory landscape of embryonic multipotent progenitor cells that give rise to all pancreatic epithelial lineages. Using human embryonic pancreas and embryonic-stem-cell-derived progenitors we identify stage-specific transcripts and associated enhancers, many of which are co-occupied by transcription factors that are essential for pancreas development. We further show that TEAD1, a Hippo signalling effector, is an integral component of the transcription factor combinatorial code of pancreatic progenitor enhancers. TEAD and its coactivator YAP activate key pancreatic signalling mediators and transcription factors, and regulate the expansion of pancreatic progenitors. This work therefore uncovers a central role for TEAD and YAP as signal-responsive regulators of multipotent pancreatic progenitors, and provides a resource for the study of embryonic development of the human pancreas

Novel genetic analysis for case-control genome-wide association studies: quantification of power and genomic prediction accuracy

Genome-wide association studies (GWAS) are routinely conducted for both quantitative and binary (disease) traits. We present two analytical tools for use in the experimental design of GWAS. Firstly, we present power calculations quantifying power in a unified framework for a range of scenarios. In this context we consider the utility of quantitative scores (e.g. endophenotypes) that may be available on cases only or both cases and controls. Secondly, we consider, the accuracy of prediction of genetic risk from genome-wide SNPs and derive an expression for genomic prediction accuracy using a liability threshold model for disease traits in a case-control design. The expected values based on our derived equations for both power and prediction accuracy agree well with observed estimates from simulations

Routes for breaching and protecting genetic privacy

We are entering the era of ubiquitous genetic information for research, clinical care, and personal curiosity. Sharing these datasets is vital for rapid progress in understanding the genetic basis of human diseases. However, one growing concern is the ability to protect the genetic privacy of the data originators. Here, we technically map threats to genetic privacy and discuss potential mitigation strategies for privacy-preserving dissemination of genetic data.Comment: Draft for comment

High throughput method for analysis of repeat number for 28 phase variable loci of C. jejuni strain NCTC11168

Mutations in simple sequence repeat tracts are a major mechanism of phase variation in several bacterial species including Campylobacter jejuni. Changes in repeat number of tracts located within the reading frame can produce a high frequency of reversible switches in gene expression between ON and OFF states. The genome of C. jejuni strain NCTC11168 contains 29 loci with polyG/polyC tracts of seven or more repeats. This protocol outlines a method for rapidly determining ON/OFF states of these 28 phase-variable loci in a large number of individual colonies. The method combines a series of multiplex PCR assays with a GeneScan assay and automated extraction of tract length, repeat number and expression state. This high throughput, multiplex assay has utility for detecting shifts in phase variation states within and between populations over time and for exploring the effects of phase variation on adaptation to differing selective pressures. An important output of this assay is combinatorial expression states that cannot be determined by other methods. This method can be adapted to analysis of phase variation in other C. jejuni strains and in a diverse range of bacterial species

An in-frame deletion at the polymerase active site of POLD1 causes a multisystem disorder with lipodystrophy

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.DNA polymerase δ, whose catalytic subunit is encoded by POLD1, is responsible for lagging-strand DNA synthesis during DNA replication. It carries out this synthesis with high fidelity owing to its intrinsic 3'- to 5'-exonuclease activity, which confers proofreading ability. Missense mutations affecting the exonuclease domain of POLD1 have recently been shown to predispose to colorectal and endometrial cancers. Here we report a recurring heterozygous single-codon deletion in POLD1 affecting the polymerase active site that abolishes DNA polymerase activity but only mildly impairs 3'- to 5'-exonuclease activity. This mutation causes a distinct multisystem disorder that includes subcutaneous lipodystrophy, deafness, mandibular hypoplasia and hypogonadism in males. This discovery suggests that perturbing the function of the ubiquitously expressed POLD1 polymerase has unexpectedly tissue-specific effects in humans and argues for an important role for POLD1 function in adipose tissue homeostasis.This work was supported by NIHR Exeter Clinical Research Facility through funding for SE and ATH and general infrastructure. The authors thank Michael Day, Annet Damhuis and Richard Gilbert for technical assistance. We thank Karen Knapp for providing the data for the DEXA calculations. SE, ATH, SO are supported by Wellcome Weedon et al. Page 6 Nat Genet. Author manuscript; available in PMC 2014 February 01. Europe PMC Funders Author Manuscripts Europe PMC Funders Author Manuscripts Trust Senior Investigator awards. DS and RKS (098498/Z/12/Z) are supported by Wellcome Trust Senior Research Fellowships in Clinical Science. MNW is supported by the Wellcome Trust as part of the WT Biomedical Informatics Hub funding. RO is supported by Diabetes UK. DS, RKS and SO are supported by the UK National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. KJG is supported by the Agency for Science, Technology and Research, Singapore (A*STAR). LAL and MJP are supported by grants NCI-61-6845 and 62-4860

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

A rare SNP in pre-miR-34a is associated with increased levels of miR-34a in pancreatic beta cells.

Open Access Article.Changes in the levels of specific microRNAs (miRNAs) can reduce glucose-stimulated insulin secretion and increase beta-cell apoptosis, two causes of islet dysfunction and progression to type 2 diabetes. Studies have shown that single nucleotide polymorphisms (SNPs) within miRNA genes can affect their expression. We sought to determine whether miRNAs, with a known role in beta-cell function, possess SNPs within the pre-miRNA structure which can affect their expression. Using published literature and dbSNP, we aimed to identify miRNAs with a role in beta-cell function that also possess SNPs within the region encoding its pre-miRNA. Following transfection of plasmids, encoding the pre-miRNA and each allele of the SNP, miRNA expression was measured. Two rare SNPs located within the pre-miRNA structure of two miRNA genes important to beta-cell function (miR-34a and miR-96) were identified. Transfection of INS-1 and MIN6 cells with plasmids encoding pre-miR-34a and the minor allele of rs72631823 resulted in significantly (p < 0.05) higher miR-34a expression, compared to cells transfected with plasmids encoding the corresponding major allele. Similarly, higher levels were also observed upon transfection of HeLa cells. Transfection of MIN6 cells with plasmids encoding pre-miR-96 and each allele of rs41274239 resulted in no significant differences in miR-96 expression. A rare SNP in pre-miR-34a is associated with increased levels of mature miR-34a. Given that small changes in miR-34a levels have been shown to cause increased levels of beta-cell apoptosis this finding may be of interest to studies looking at determining the effect of rare variants on type 2 diabetes susceptibility