High genetic diversity at the extreme range edge: nucleotide variation at nuclear loci in Scots pine (Pinus sylvestris L.) in Scotland

Nucleotide polymorphism at 12 nuclear loci was studied in Scots pine populations across an environmental gradient in Scotland, to evaluate the impacts of demographic history and selection on genetic diversity. At eight loci, diversity patterns were compared between Scottish and continental European populations. At these loci, a similar level of diversity (θsil=~0.01) was found in Scottish vs mainland European populations, contrary to expectations for recent colonization, however, less rapid decay of linkage disequilibrium was observed in the former (ρ=0.0086±0.0009, ρ=0.0245±0.0022, respectively). Scottish populations also showed a deficit of rare nucleotide variants (multi-locus Tajima's D=0.316 vs D=−0.379) and differed significantly from mainland populations in allelic frequency and/or haplotype structure at several loci. Within Scotland, western populations showed slightly reduced nucleotide diversity (πtot=0.0068) compared with those from the south and east (0.0079 and 0.0083, respectively) and about three times higher recombination to diversity ratio (ρ/θ=0.71 vs 0.15 and 0.18, respectively). By comparison with results from coalescent simulations, the observed allelic frequency spectrum in the western populations was compatible with a relatively recent bottleneck (0.00175 × 4Ne generations) that reduced the population to about 2% of the present size. However, heterogeneity in the allelic frequency distribution among geographical regions in Scotland suggests that subsequent admixture of populations with different demographic histories may also have played a role

Protection of Visual Functions by Human Neural Progenitors in a Rat Model of Retinal Disease

BACKGROUND: A promising clinical application for stem and progenitor cell transplantation is in rescue therapy for degenerative diseases. This strategy seeks to preserve rather than restore host tissue function by taking advantage of unique properties often displayed by these versatile cells. In studies using different neurodegenerative disease models, transplanted human neural progenitor cells (hNPC) protected dying host neurons within both the brain and spinal cord. Based on these reports, we explored the potential of hNPC transplantation to rescue visual function in an animal model of retinal degeneration, the Royal College of Surgeons rat. METHODOLOGY/PRINCIPAL FINDINGS: Animals received unilateral subretinal injections of hNPC or medium alone at an age preceding major photoreceptor loss. Principal outcomes were quantified using electroretinography, visual acuity measurements and luminance threshold recordings from the superior colliculus. At 90–100 days postnatal, a time point when untreated rats exhibit little or no retinal or visual function, hNPC-treated eyes retained substantial retinal electrical activity and visual field with near-normal visual acuity. Functional efficacy was further enhanced when hNPC were genetically engineered to secrete glial cell line-derived neurotrophic factor. Histological examination at 150 days postnatal showed hNPC had formed a nearly continuous pigmented layer between the neural retina and retinal pigment epithelium, as well as distributed within the inner retina. A concomitant preservation of host cone photoreceptors was also observed. CONCLUSIONS/SIGNIFICANCE: Wild type and genetically modified human neural progenitor cells survive for prolonged periods, migrate extensively, secrete growth factors and rescue visual functions following subretinal transplantation in the Royal College of Surgeons rat. These results underscore the potential therapeutic utility of hNPC in the treatment of retinal degenerative diseases and suggest potential mechanisms underlying their effect in vivo

Analysis of SLX4/FANCP in non-BRCA1/2-mutated breast cancer families

<p>Abstract</p> <p>Background</p> <p>Genes that, when mutated, cause Fanconi anemia or greatly increase breast cancer risk encode for proteins that converge on a homology-directed DNA damage repair process. Mutations in the <it>SLX4 </it>gene, which encodes for a scaffold protein involved in the repair of interstrand cross-links, have recently been identified in unclassified Fanconi anemia patients. A mutation analysis of <it>SLX4 </it>in German or Byelorussian familial cases of breast cancer without detected mutations in <it>BRCA1 </it>or <it>BRCA2 </it>has been completed, with globally negative results.</p> <p>Methods</p> <p>The genomic region of <it>SLX4</it>, comprising all exons and exon-intron boundaries, was sequenced in 94 Spanish familial breast cancer cases that match a criterion indicating the potential presence of a highly-penetrant germline mutation, following exclusion of <it>BRCA1 </it>or <it>BRCA2 </it>mutations.</p> <p>Results</p> <p>This mutational analysis revealed extensive genetic variation of <it>SLX4</it>, with 21 novel single nucleotide variants; however, none could be linked to a clear alteration of the protein function. Nonetheless, genotyping 10 variants (nine novel, all missense amino acid changes) in a set of controls (138 women and 146 men) did not detect seven of them.</p> <p>Conclusions</p> <p>Overall, while the results of this study do not identify clearly pathogenic mutations of <it>SLX4 </it>contributing to breast cancer risk, further genetic analysis, combined with functional assays of the identified rare variants, may be warranted to conclusively assess the potential link with the disease.</p

Urinary heavy metals, phthalates, perchlorate, nitrate, thiocyanate, hydrocarbons, and polyfluorinated compounds are associated with adult hearing disturbance: USA NHANES, 2011–2012

Background Links between environmental chemicals and human health have emerged, but the effects on hearing were less studied. Therefore, the aim of the present study was to investigate the relationships of different sets of environmental chemicals and the hearing conditions in a national and population-based setting. Methods Data was retrieved from the US National Health and Nutrition Examination Surveys, 2011–2012 including demographics, serum measurements, lifestyle factors, self-reported hearing conditions, and urinary environmental chemical concentrations. Chi-square test, t test, and survey-weighted logistic regression models were performed. Results Among the American adults aged 20–69 (n=5560), 462 (8.3 %) people reported their hearing condition as moderate trouble to deaf. They had higher levels of urinary hydrocarbons and polyfluorinated compounds but not heavy metals, phthalates, arsenic, pesticides, phenols, parabens, perchlorate, nitrate, and thiocyanate concentrations. Also, 466 (10.0 %) people had hearing difficulties during conversation. They had higher levels of urinary cobalt (odds ratio (OR) 1.27, 95 % confidence interval (95%CI) 1.00–1.63), molybdenum (OR 1.45, 95%CI 1.04–2.02), strontium (OR 1.56, 95%CI 1.10–2.21), phthalates, perchlorate (OR 1.27, 95%CI 1.05– 1.54), nitrate (OR 1.60, 1.03–2.49) and thiocyanate (OR 1.22, 95%CI 1.01–1.48) concentrations but not arsenic, pesticides, phenols, parabens, hydrocarbons, and polyfluorinated compounds. Moreover, people who reported difficulties in following conversation with background noise had higher levels of urinary tin concentrations (OR 1.17, 1.00–1.36). Conclusions Urinary heavy metals, phthalates, perchlorate, nitrate, thiocyanate, hydrocarbons, and polyfluorinated compounds were associated with the adult hearing disturbance, although the causality cannot be established. Elimination of these environmental chemicals might need to be considered in future environmental health policy and health intervention programs

Cocoa Certification in West Africa: The Need for Change

The goal of this chapter is to discuss various implementation challenges of current cocoa certification schemes at the farm level in West Africa. To this end, the chapter presents a selection of certification criteria (requirements) from the two leading certification schemes: UTZ Certified and Rainforest Alliance. The criteria selected exemplify typical implementation problems in the West African cocoa sector, though they are by no means an exhaustive list

Conceptualising and Measuring Social Capital as a Sustainable Development Strategy in Mewat Region, Haryana

This paper attempts to conceptualize and measure social capital as a sustainable development strategy in Mewat region, Haryana. Social capital resides in relations of the people that they can use for their benefits. Social capital here is reconceptualised as an instrumental use of social relations for the mutual benefit of the communities. Social capital is contextual and is best captured as a multidimensional variable. For lack of secondary data, this study relies on a primary field survey of ten sample Panchayat Villages in Mewat, Haryana. Sample Panchayats are identified through cluster random sampling and use measures of associatedness (economic, social and political), relations of production, institutions, social cohesion, and social pathologies as a set of variables. A mixed methods approach is used to analyze the variables. The empirical results show that socio-cultural activity has the highest level of associatedness followed by economic and political activities. The results show that self-help groups are an important source of social capital along with associatedness in socio-cultural activities, increase in mutually beneficial production relations, vibrant institutions and strong social cohesion. The paper concludes that social capital along with economic capital can be employed as a strategy of sustainable development in Mewat region, Haryana