Examination of faecal Bifidobacterium populations in breast- and formula-fed infants during the first 18 months of life.

Bifidobacteria in the infant faecal microbiota have been the focus of much interest, especially during the exclusive milk-feeding period and in relation to the fortification of infant formulae to better mimic breast milk. However, longitudinal studies examining the diversity and dynamics of the Bifidobacterium population of infants are lacking, particularly in relation to the effects of weaning. Using a polyphasic strategy, the Bifidobacterium populations of breast- and formula-fed infants were examined during the first 18 months of life. Bifidobacterium-specific denaturing gradient gel electrophoresis demonstrated that breast-fed infants harboured greater diversity than formula-fed infants and the diversity of the infants' Bifidobacterium populations increased with weaning. Twenty-seven distinctive banding profiles were observed from ∼1100 infant isolates using ribosomal intergenic spacer analysis, 14 biotypes of which were confirmed to be members of the genus Bifidobacterium. Two profiles (H, Bifidobacterium longum subsp. infantis; and I, Bifidobacterium bifidum) were common culturable biotypes, seen in 9/10 infants, while profile E (Bifidobacterium breve) was common among breast-fed infants. Overall, inter- and intra-individual differences were observed in the Bifidobacterium populations of infants between 1 and 18 months of age, although weaning was associated with increased diversity of the infant Bifidobacterium populations. Breast-fed infants generally harboured a more complex Bifidobacterium microbiota than formula-fed infants.

Pathogenic LRRK2 mutations do not alter gene expression in cell model systems or human brain tissue

Point mutations in LRRK2 cause autosomal dominant Parkinson's disease. Despite extensive efforts to determine the mechanism of cell death in patients with LRRK2 mutations, the aetiology of LRRK2 PD is not well understood. To examine possible alterations in gene expression linked to the presence of LRRK2 mutations, we carried out a case versus control analysis of global gene expression in three systems: fibroblasts isolated from LRRK2 mutation carriers and healthy, non-mutation carrying controls; brain tissue from G2019S mutation carriers and controls; and HEK293 inducible LRRK2 wild type and mutant cell lines. No significant alteration in gene expression was found in these systems following correction for multiple testing. These data suggest that any alterations in basal gene expression in fibroblasts or cell lines containing mutations in LRRK2 are likely to be quantitatively small. This work suggests that LRRK2 is unlikely to play a direct role in modulation of gene expression, although it remains possible that this protein can influence mRNA expression under pathogenic cicumstances.

Planetary-wave-induced transport in the stratosphere

In the stratosphere, chemical tracers are drawn systematically from the equator to the pole. This observed Brewer–Dobson circulation is driven by wave drag, which in the stratosphere arises mainly from the breaking and dissipation of planetary-scale Rossby waves. While the overall sense of the circulation follows from fundamental physical principles, a quantitative theoretical understanding of the connection between wave drag and Lagrangian transport is limited to linear, small-amplitude waves. However, planetary waves in the stratosphere generally grow to a large amplitude and break in a strongly nonlinear fashion. This paper addresses the connection between stratospheric wave drag and Lagrangian transport in the presence of strong nonlinearity, using a mechanistic three-dimensional primitive equations model together with offline particle advection. Attention is deliberately focused on a weak forcing regime, such that sudden warmings do not occur and a quasi-steady state is reached, in order to examine this question in the cleanest possible context. Wave drag is directly linked to the transformed Eulerian mean (TEM) circulation, which is often used as a surrogate for mean Lagrangian motion. The results show that the correspondence between the TEM and mean Lagrangian velocities is quantitatively excellent in regions of linear, nonbreaking waves (i.e., outside the surf zone), where streamlines are not closed. Within the surf zone, where streamlines are closed and meridional particle displacements are large, the agreement between the vertical components of the two velocity fields is still remarkably good, especially wherever particle paths are coherent so that diabatic dispersion is minimized. However, in this region the meridional mean Lagrangian velocity bears little relation to the meridional TEM velocity, and reflects more the kinematics of mixing within and across the edges of the surf zone. The results from the mechanistic model are compared with those from the Canadian Middle Atmosphere Model to test the robustness of the conclusions.

Impact evaluation of a Kenyan Eco Business: a pilot framework.

Promoting social and environmental entrepreneurship is suggested by many, including international institutions, national development agencies and non-governmental organizations, as critical in tackling longstanding complex global sustainable development problems. However while interest in this kind of alternative entrepreneurship grows, with a proliferation of claims made about its potential to catalyze societal transformation, research in this field remains nascent and fragmented, particularly in relation to Africa. There are few examples of work systematically examining the impacts of social and environmental enterprises on sustainable development and poverty alleviation, especially research based on rigorous empirical fieldwork. This paper begins addressing these limitations by proposing a framework for mapping the sustainable development and poverty alleviation impacts of social and environmental enterprises in Africa. This framework is then piloted with reference to a Kenyan ecobusiness.

Mapping the trickle out benefits of social and environmental enterprises: a pilot study of an East African eco business

• Objectives The objective of this paper is to propose a framework for mapping the sustainable development and poverty alleviation impacts of social and environmental enterprises in Africa. This framework is then piloted with reference to an East African Ecobusiness. • Prior Work This paper is based on data collected as part of a wider research project examining social and environmental enterprises across the 19 countries of Southern and Eastern Africa. In total, the sustainable development and poverty alleviation impacts of 20 in-depth case studies in 4 countries are being examined. • Approach Data was collected using in-depth interviews with multiple stakeholders associated with the case study business. Secondary materials were also analysed and a quantitative survey of customers undertaken. • Results In addition to their impacts on the environment, African eco businesses can also have substantial social, economic and wider poverty alleviation impacts. This paper maps the impacts of a case study East African ecobusiness, as part of developing a social and environmental enterprise impact framework for Africa and the wider developing world. In our case study, positive and negative impacts are identified, while questions are raised in relation to tradeoffs between social and environmental objectives and temporal dimensions of impact. The usefulness of existing frameworks for understanding the social, environmental and development impacts of these kinds of organisations are also considered. • Implications This paper outlines the necessity of building an African-centric impact map to capture the multi-level poverty alleviation and sustainable development impacts of social and environmental enterprise activity in developing world environments. The framework proposed also offers guidance to businesses operating in Africa about the factors that might be considered as part of their wider social and environmental responsibilities. • Value Assessing the impact of social and environmental enterprises, especially as a route to development within low income countries, is receiving increasing attention in academia and beyond. This paper presents a useful contribution to the scarce literature on social and environmental enterprises in Africa.

The Jua Kali and the Mali-Mali: the informal/formal nexus amongst Kenyan micro enterprises

This paper presents a preliminary exploration of the informal/formal economy nexus and entrepreneurial processes amongst a sample of Kenyan roadside vendors who mostly operate in the informal economy. Using semi-structured interviews, data was collected from sixty street vendors across Kenya. In particular the paper focuses on the relationship between the informal and formal economy and the factors that promote formality amongst micro and small enterprises in developing countries. The paper presents a conceptualization of a potential segmentation of the informal economy, considering the implications of this in terms of base of the pyramid initiatives and the promotion of development through enterprise.

Imitation, entrepreneurship and the informal/formal economy nexus: an African perspective

This paper explores a segmentation of micro and small enterprises (MSEs) in developing countries within the formal/informal economy nexus that has wide-ranging implications for the targeting of base-of-the-pyramid initiatives and entrepreneurship theory. This proposed segmentation emerges from the analysis of a sample of Kenyan MSEs utilising current and prior business models; the antecedent influences shaping the business model; barriers to entry associated with knowledge, capital and skills; the degree of innovation or imitation evident in the business model linked to the nature of opportunity recognition; and their relationship with the formal institutional business environment.

Causal relationship between obesity and vitamin D status: bi-directional mendelian randomization analysis of multiple cohorts

BACKGROUND: Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. METHODS AND FINDINGS: We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH)D (p = 6.52×10⁻²⁷). The BMI allele score was associated both with BMI (p = 6.30×10⁻⁶²) and 25(OH)D (-0.06% [95% CI -0.10 to -0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D (p≤8.07×10⁻⁵⁷ for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p = 0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p≥0.57 for both vitamin D scores). CONCLUSIONS: On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency.

Evaluation of genetic markers as instruments for Mendelian randomization studies on vitamin D

Combining SNPs into allele scores provides a more powerful instrument for MR analysis than a single SNP in isolation. Population stratification and the potential for pleiotropic effects need to be considered in MR studies on vitamin D.

A genome-wide association meta-analysis identifies new childhood obesity loci

Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight newly discovered signals yielding association with P < 5 × 10(-6) in nine independent data sets (2,818 cases and 4,083 controls), we observed two loci that yielded genome-wide significant combined P values near OLFM4 at 13q14 (rs9568856; P = 1.82 × 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 × 10(-9); OR = 1.14). Both loci continued to show association when two extreme childhood obesity cohorts were included (2,214 cases and 2,674 controls). These two loci also yielded directionally consistent associations in a previous meta-analysis of adult BMI(1).

Interaction between allelic variations in vitamin D receptor and retinoid X receptor genes on metabolic traits

BACKGROUND: Low vitamin D status has been shown to be a risk factor for several metabolic traits such as obesity, diabetes and cardiovascular disease. The biological actions of 1, 25-dihydroxyvitamin D, are mediated through the vitamin D receptor (VDR), which heterodimerizes with retinoid X receptor, gamma (RXRG). Hence, we examined the potential interactions between the tagging polymorphisms in the VDR (22 tag SNPs) and RXRG (23 tag SNPs) genes on metabolic outcomes such as body mass index, waist circumference, waist-hip ratio (WHR), high- and low-density lipoprotein (LDL) cholesterols, serum triglycerides, systolic and diastolic blood pressures and glycated haemoglobin in the 1958 British Birth Cohort (1958BC, up to n = 5,231). We used Multifactor- dimensionality reduction (MDR) program as a non-parametric test to examine for potential interactions between the VDR and RXRG gene polymorphisms in the 1958BC. We used the data from Northern Finland Birth Cohort 1966 (NFBC66, up to n = 5,316) and Twins UK (up to n = 3,943) to replicate our initial findings from 1958BC. RESULTS: After Bonferroni correction, the joint-likelihood ratio test suggested interactions on serum triglycerides (4 SNP - SNP pairs), LDL cholesterol (2 SNP - SNP pairs) and WHR (1 SNP - SNP pair) in the 1958BC. MDR permutation model testing analysis showed one two-way and one three-way interaction to be statistically significant on serum triglycerides in the 1958BC. In meta-analysis of results from two replication cohorts (NFBC66 and Twins UK, total n = 8,183), none of the interactions remained after correction for multiple testing (Pinteraction >0.17). CONCLUSIONS: Our results did not provide strong evidence for interactions between allelic variations in VDR and RXRG genes on metabolic outcomes; however, further replication studies on large samples are needed to confirm our findings.

Analysis of DNA polymorphism in ancient barley herbarium material: validation of the KASP SNP genotyping platform

The availability of crop specimens archived in herbaria and old seed collections represent valuable resources for the analysis of plant genetic diversity and crop domestication. The ability to extract ancient DNA (aDNA) from such samples has recently allowed molecular genetic investigations to be undertaken in ancient materials. While analyses of aDNA initially focused on the use of markers which occur in multiple copies such as the internal transcribed spacer region (ITS) within ribosomal DNA and those requiring amplification of short DNA regions of variable length such as simple sequence repeats (SSRs), emphasis is now moving towards the genotyping of single nucleotide polymorphisms (SNPs), traditionally undertaken in aDNA by Sanger sequencing. Here, using a panel of barley aDNA samples previously surveyed by Sanger sequencing for putative causative SNPs within the flowering-time gene PPD-H1, we assess the utility of the Kompetitive Allele Specific PCR (KASP) genotyping platform for aDNA analysis. We find KASP to out-perform Sanger sequencing in the genotyping of aDNA samples (78% versus 61% success, respectively), as well as being robust to contamination. The small template size (≥46 bp) and one-step, closed-tube amplification/genotyping process make this platform ideally suited to the genotypic analysis of aDNA, a process which is often hampered by template DNA degradation and sample cross-contamination. Such attributes, as well as its flexibility of use and relatively low cost, make KASP particularly relevant to the genetic analysis of aDNA samples. Furthermore, KASP provides a common platform for the genotyping and analysis of corresponding SNPs in ancient, landrace and modern plant materials. The extended haplotype analysis of PPD-H1 undertaken here (allelic variation at which is thought to be important for the spread of domestication and local adaptation) provides further resolution to the previously identified geographic cline of flowering-time allele distribution, illustrating how KASP can be used to aid genetic analyses of aDNA from plant species. We further demonstrate the utility of KASP by genotyping ten additional genetic markers diagnostic for morphological traits in barley, shedding light on the phenotypic traits, alleles and allele combinations present in these unviable ancient specimens, as well as their geographic distributions.