Identification of Carbohydrate Metabolism Genes in the Metagenome of a Marine Biofilm Community Shown to Be Dominated by Gammaproteobacteria and Bacteroidetes

Polysaccharides are an important source of organic carbon in the marine environment and degradation of the insoluble and globally abundant cellulose is a major component of the marine carbon cycle. Although a number of species of cultured bacteria are known to degrade crystalline cellulose, little is known of the polysaccharide hydrolases expressed by cellulose-degrading microbial communities, particularly in the marine environment. Next generation 454 Pyrosequencing was applied to analyze the microbial community that colonizes and degrades insoluble polysaccharides in situ in the Irish Sea. The bioinformatics tool MG-RAST was used to examine the randomly sampled data for taxonomic markers and functional genes, and showed that the community was dominated by members of the Gammaproteobacteria and Bacteroidetes. Furthermore, the identification of 211 gene sequences matched to a custom-made database comprising the members of nine glycoside hydrolase families revealed an extensive repertoire of functional genes predicted to be involved in cellulose utilization. This demonstrates that the use of an in situ cellulose baiting method yielded a marine microbial metagenome considerably enriched in functional genes involved in polysaccharide degradation. The research reported here is the first designed to specifically address the bacterial communities that colonize and degrade cellulose in the marine environment and to evaluate the glycoside hydrolase (cellulase and chitinase) gene repertoire of that community, in the absence of the biases associated with PCR-based molecular techniques

National movement patterns during the COVID-19 pandemic in New Zealand:The unexplored role of neighbourhood deprivation

BACKGROUND: The COVID-19 pandemic has asked unprecedented questions of governments around the world. Policy responses have disrupted usual patterns of movement in society, locally and globally, with resultant impacts on national economies and human well-being. These interventions have primarily centred on enforcing lockdowns and introducing social distancing recommendations, leading to questions of trust and competency around the role of institutions and the administrative apparatus of state. This study demonstrates the unequal societal impacts in population movement during a national ‘lockdown’. METHODS: We use nationwide mobile phone movement data to quantify the effect of an enforced lockdown on population mobility by neighbourhood deprivation using an ecological study design. We then derive a mobility index using anonymised aggregated population counts for each neighbourhood (2253 Census Statistical Areas; mean population n=2086) of national hourly mobile phone location data (7.45 million records, 1 March 2020–20 July 2020) for New Zealand (NZ). RESULTS: Curtailing movement has highlighted and exacerbated underlying social and spatial inequalities. Our analysis reveals the unequal movements during ‘lockdown’ by neighbourhood socioeconomic status in NZ. CONCLUSION: In understanding inequalities in neighbourhood movements, we are contributing critical new evidence to the policy debate about the impact(s) and efficacy of national, regional or local lockdowns which have sparked such controversy

co_LAB - Project 1

co_LAB is an interdisciplinary, educational project which houses intensive teaching programmes, the first of which took place between 12-16 May, 2014. co_LAB was designed to explore and develop new approaches to collaborative teaching and learning through the use of networked digital tools, and through the transferral of knowledge, skillsets and teaching styles. co_LAB aims to overcome the traditional barriers between individual course specialisms by bringing together students and colleagues from across academic disciplines to collaborate on transmedia design projects. co_LAB team: Martyn Thayne, James Field, Graham Cooper, Rob Coley, Richard Vickers, Adam Verity, Clive McCarthy (special thanks to Louise Lawlor, Mike Downing, Mark Aldridge, John Murray, Chris Heydra (The Hague University of Applied Sciences

Мероприятия по предупреждению травматизма на ООО "Газпром Трансгаз Томск"

A series of macrocyclic peptidic BACE-1 inhibitors was designed. While potency on BACE-1 was rather high, the first set of compounds showed poor brain permeation and high efflux in the MDCK-MDR1 assay. The replacement of the secondary benzylamino group with a phenylcyclopropylamino group maintained potency on BACE-1, while p-glycoprotein-mediated efflux was significantly reduced and brain permeation improved. Several compounds from this series demonstrated acute reduction of Abeta in human APP-wildtype transgenic (APP51) mice after oral administration

Psychopathic leadership a case study of a corporate psychopath CEO

This longitudinal case study reports on a charity in the UK which gained a new CEO who was reported by two middle managers who worked in the charity, to embody (respectively) all or most of the ten characteristics within a measure of corporate psychopathy. The leadership of this CEO with a high corporate psychopathy score was reported to be so poor that the organisation was described as being one without leadership and as a lost organisation with no direction. This paper outlines the resultant characteristics of the ensuing aimlessness and lack of drive of the organisation involved. Comparisons are made to a previous CEO in the same organisation, who was reportedly an authentic, effective and transformational leader. Outcomes under the CEO with a high corporate psychopathy score were related to bullying, staff withdrawal and turnover as effective employees stayed away from and/or left the organisation. Outcomes also included a marked organisational decline in terms of revenue, employee commitment, creativity and organisational innovativeness. The paper makes a contribution to both leadership and to corporate psychopathy research as it appears to be the first reported study of a CEO with a high corporate psychopathy score

Genome-Wide Association Identifies Nine Common Variants Associated With Fasting Proinsulin Levels and Provides New Insights Into the Pathophysiology of Type 2 Diabetes

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10−8). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10−4), improved β-cell function (P = 1.1 × 10−5), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10−6). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group

Association of vitamin D status with arterial blood pressure and hypertension risk : a mendelian randomisation study

Peer reviewe

Genome-Wide Association Study Reveals Multiple Loci Associated with Primary Tooth Development during Infancy

Tooth development is a highly heritable process which relates to other growth and developmental processes, and which interacts with the development of the entire craniofacial complex. Abnormalities of tooth development are common, with tooth agenesis being the most common developmental anomaly in humans. We performed a genome-wide association study of time to first tooth eruption and number of teeth at one year in 4,564 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966) and 1,518 individuals from the Avon Longitudinal Study of Parents and Children (ALSPAC). We identified 5 loci at P<5×10−8, and 5 with suggestive association (P<5×10−6). The loci included several genes with links to tooth and other organ development (KCNJ2, EDA, HOXB2, RAD51L1, IGF2BP1, HMGA2, MSRB3). Genes at four of the identified loci are implicated in the development of cancer. A variant within the HOXB gene cluster associated with occlusion defects requiring orthodontic treatment by age 31 years