Genetic variations in androgen metabolism genes and associations with prostate cancer in South African men

Background. In South Africa white men have the highest incidence of prostate cancer (PCa), coloured (mixed ancestry) men have an intermediate incidence, and low incidences are reported for black and Asian men. It has been suggested that ethnic differences in incidence and mortality of PCa are related to genetic variations in genes that regulate androgen metabolism. We investigated the role of genetic variants in the androgen metabolism genes and the probability of developing PCa in South African coloured and white men. Methods. Genotype and allele counts and frequencies of single nucleotide polymorphisms (SNPs) in CYP3A5, CYP3A4 and CYP3A43 were assessed in coloured men (160 case individuals, 146 control individuals) and white men (121 case individuals, 141 control individuals). Results. A genetic association indicating an increased probability of developing PCa was observed with the G allele of the SNP rs2740574 in CYP3A4 in coloured men, the A allele of rs776746 (CYP3A5) and the G allele of rs2740574 (CYP3A4) in white men, and the G allele of rs2740574 and the C allele of rs501275 (CYP3A43) in the combined ethnic groups analysis. In addition, we identified allele combinations (termed haplotypes) with significantly higher frequencies in the PCa case individuals than in the control individuals. Conclusions. The findings support the role of variants in genes that regulate androgen metabolism and the probability of developing PCa. The study paves the way to identify other genetic associations in South African men, and to establish genetic profiles that could be used to determine disease progression and prognosis

The 'law of requisite variety' may assist climate change negotiations:a review of the Kyoto and Durban meetings

Ashby wrote about cybernetics, during which discourse he described a Law that attempts to resolve difficulties arising in complex situations – he suggested using variety to combat complexity. In this paper, we note that the delegates to the UN Framework Convention on Climate Change (UNFCCC) meeting in Kyoto, 1997, were offered a ‘simplifying solution’ to cope with the complexity of discussing multiple pollutants allegedly contributing to ‘climate change’. We assert that the adoption of CO2eq has resulted in imprecise thinking regarding the ‘carbon footprint’ – that is, ‘CO2’ – to the exclusion of other pollutants. We propose, as Ashby might have done, that the CO2eq and other factors within the ‘climate change’ negotiations be disaggregated to allow careful and specific individual solutions to be agreed on each factor. We propose a new permanent and transparent ‘action group’ be in charge of agenda setting and to manage the messy annual meetings. This body would be responsible for achieving accords at these annual meetings, rather than forcing this task on national hosts. We acknowledge the task is daunting and we recommend moving on from Ashby's Law to Beer's Viable Systems approach

Drinking behaviour and alcohol-related harm amongst older adults: analysis of existing UK datasets.

Older adults experience age-related physiological changes that increase sensitivity and decrease tolerance to alcohol and there are a number of age-related harms such as falls, social isolation and elder abuse, which are compounded by alcohol misuse. Despite this unique vulnerability and the fact that the number of older adults is increasing, the literature on drinking behaviour and alcohol-related harm in older adults is sparse. This article describes a secondary analysis of UK data to address this knowledge gap

Finding needles in haystacks: linking scientific names, reference specimens and molecular data for Fungi

DNA phylogenetic comparisons have shown that morphology-based species recognition often underestimates fungal diversity. Therefore, the need for accurate DNA sequence data, tied to both correct taxonomic names and clearly annotated specimen data, has never been greater. Furthermore, the growing number of molecular ecology and microbiome projects using high-throughput sequencing require fast and effective methods for en masse species assignments. In this article, we focus on selecting and re-annotating a set of marker reference sequences that represent each currently accepted order of Fungi. The particular focus is on sequences from the internal transcribed spacer region in the nuclear ribosomal cistron, derived from type specimens and/or ex-type cultures. Re-annotated and verified sequences were deposited in a curated public database at the National Center for Biotechnology Information (NCBI), namely the RefSeq Targeted Loci (RTL) database, and will be visible during routine sequence similarity searches with NR_prefixed accession numbers. A set of standards and protocols is proposed to improve the data quality of new sequences, and we suggest how type and other reference sequences can be used to improve identification of Fungi

Sustainable procurement strategies for competitive advantage: An empirical study

Procurement plays a key role in sustainability as policies and practices need to extend beyond organisations' boundaries to incorporate their whole supply chains. There is, however, a paucity of empirical research on sustainable forms of procurement initiatives currently being implemented in the UK construction sector to improve competitiveness - which is the core driver of this paper. In order to achieve this aim, a mixed research methodological approach was adopted to collect and analyse data. The findings are based primarily on quantitative data obtained from 53 completed postal questionnaires and semi-structured interviews with 17 professionals from 12 UK construction organisations. As revealed by this study, sustainable procurement is becoming increasingly important in the UK construction sector. The paper concludes that the process of integrating sustainable procurement initiatives into existing business models is often a complex issue. Therefore, there is an urgent need to explore the drivers and impediments associated with the successful integration of sustainable procurement initiatives into existing construction business models. It is also suggested that there is a need for cross-sector collaboration to capture and share best and worst practices relating to sustainable procurement strategies

Association of rs780094 in GCKR with Metabolic Traits and Incident Diabetes and Cardiovascular Disease: The ARIC Study

The minor T-allele of rs780094 in the glucokinase regulator gene (GCKR) associates with a number of metabolic traits including higher triglyceride levels and improved glycemic regulation in study populations of mostly European ancestry. Using data from the Atherosclerosis Risk in Communities (ARIC) Study, we sought to replicate these findings, examine them in a large population-based sample of African American study participants, and to investigate independent associations with other metabolic traits in order to determine if variation in GKCR contributes to their observed clustering. In addition, we examined the association of rs780094 with incident diabetes, coronary heart disease (CHD), and stroke over up mean follow-up times of 8, 15, and 15 years, respectively.Race-stratified analyses were conducted among 10,929 white and 3,960 black participants aged 45-64 at baseline assuming an additive genetic model and using linear and logistic regression and Cox proportional hazards models.Previous findings replicated among white participants in multivariable adjusted models: the T-allele of rs780094 was associated with lower fasting glucose (p = 10(-7)) and insulin levels (p = 10(-6)), lower insulin resistance (HOMA-IR, p = 10(-9)), less prevalent diabetes (p = 10(-6)), and higher CRP (p = 10(-8)), 2-h postprandial glucose (OGTT, p = 10(-6)), and triglyceride levels (p = 10(-31)). Moreover, the T-allele was independently associated with higher HDL cholesterol levels (p = 0.022), metabolic syndrome prevalence (p = 0.043), and lower beta-cell function measured as HOMA-B (p = 0.011). Among black participants, the T-allele was associated only with higher triglyceride levels (p = 0.004) and lower insulin levels (p = 0.002) and HOMA-IR (p = 0.013). Prospectively, the T-allele was associated with reduced incidence of diabetes (p = 10(-4)) among white participants, but not with incidence of CHD or stroke.Our findings indicate rs780094 has independent associations with multiple metabolic traits as well as incident diabetes, but not incident CHD or stroke. The magnitude of association between the SNP and most traits was of lower magnitude among African American compared to white participants

Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression

Long-term carbon loss in fragmented Neotropical forests

Tropical forests play an important role in the global carbon cycle, as they store a large amount of carbon (C). Tropical forest deforestation has been identified as a major source of CO2 emissions, though biomass loss due to fragmentation—the creation of additional forest edges—has been largely overlooked as an additional CO2 source. Here, through the combination of remote sensing and knowledge on ecological processes, we present long-term carbon loss estimates due to fragmentation of Neotropical forests: within 10 years the Brazilian Atlantic Forest has lost 69 (±14) Tg C, and the Amazon 599 (±120) Tg C due to fragmentation alone. For all tropical forests, we estimate emissions up to 0.2 Pg C y−1 or 9 to 24% of the annual global C loss due to deforestation. In conclusion, tropical forest fragmentation increases carbon loss and should be accounted for when attempting to understand the role of vegetation in the global carbon balance.This study was part of the project ‘Biodiversity conservation in a fragmented landscape at the Atlantic Plateau of São Paulo’ (BIOTA/Caucaia and BioCAPSP) funded by FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo, project no. 99/05123-4, 01/13309-2, 02/02125-0, 02/02126-7), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, project no. 690144/01-6), Fundação O Boticário de Proteção à Natureza, and by BMBF (German Federal Ministry of Education and Research, project n. 01LB0202). J.P.M. and M.C.R. thank the Brazilian Science Council (Conselho Nacional de Desenvolvimento Científico) for his research fellowship (process no. 307934/2011-0 and 312045/2013-1, respectively). A.H. and S.P. were supported by the ERC advanced grant 233066. M.M. has been supported by BMBF (project n. 01LB0202), and the Department of Ecological Modelling of the Helmholtz Centre for Environmental Research (UFZ). We thank Birgit Felinks for the support during the Mata Atlântica project. Florian Hartig provided valuable comments on an earlier version of this manuscript. S.P. has been funded by the Helmholtz Association of German Research Centres within the project ‘Biomass and Bioenergy systems’. A.H. was also supported by the Helmholtz-Alliance Remote Sensing and Earth System Dynamics. A.H. thanks C. Wissel and H. Bossel for supporting the FORMIND project over the years

Multimodal Management of Atrophic Acne Scarring in the Aging Face

Atrophic facial acne scarring is a widely prevalent condition that can have a negative impact on a patient’s quality of life. The appearance of these scars is often worsened by the normal effects of aging. A number of options are available for the treatment of acne scarring, including chemical peeling, dermabrasion, ablative or nonablative laser resurfacing, dermal fillers, and surgical techniques such as subcision or punch excision. Depending on the type and extent of scarring, a multimodal approach is generally necessary to provide satisfactory results. Resurfacing techniques correct surface irregularities, long-lasting dermal fillers address the volume loss resulting from acne, and sub-superficial musculoaponeurotic system (SMAS) face-lift procedures counter the soft tissue laxity and ptosis associated with aging. This article briefly reviews the evolution of individual approaches to treating atrophic acne scarring, followed by case examples illustrating results that can be achieved using a multimodal approach. Representative cases from patients in their 30s, 40s, and 50s are presented. In the author’s clinical practice, multimodal approaches incorporating fractionated laser, injectable poly-l-lactic acid, and sub-SMAS face-lift procedures have achieved optimal aesthetic outcomes, high patient satisfaction, and durability of aesthetic effect over time