Metagenomic Hi-C of a Healthy Human Fecal Microbiome Transplant Donor.

We report the availability of a high-quality metagenomic Hi-C data set generated from a fecal sample taken from a healthy fecal microbiome transplant donor subject. We report on basic features of the data to evaluate their quality

Social interaction, noise and antibiotic-mediated switches in the intestinal microbiota

The intestinal microbiota plays important roles in digestion and resistance against entero-pathogens. As with other ecosystems, its species composition is resilient against small disturbances but strong perturbations such as antibiotics can affect the consortium dramatically. Antibiotic cessation does not necessarily restore pre-treatment conditions and disturbed microbiota are often susceptible to pathogen invasion. Here we propose a mathematical model to explain how antibiotic-mediated switches in the microbiota composition can result from simple social interactions between antibiotic-tolerant and antibiotic-sensitive bacterial groups. We build a two-species (e.g. two functional-groups) model and identify regions of domination by antibiotic-sensitive or antibiotic-tolerant bacteria, as well as a region of multistability where domination by either group is possible. Using a new framework that we derived from statistical physics, we calculate the duration of each microbiota composition state. This is shown to depend on the balance between random fluctuations in the bacterial densities and the strength of microbial interactions. The singular value decomposition of recent metagenomic data confirms our assumption of grouping microbes as antibiotic-tolerant or antibiotic-sensitive in response to a single antibiotic. Our methodology can be extended to multiple bacterial groups and thus it provides an ecological formalism to help interpret the present surge in microbiome data.Comment: 20 pages, 5 figures accepted for publication in Plos Comp Bio. Supplementary video and information availabl

A systematic review of strategies to recruit and retain primary care doctors

Background There is a workforce crisis in primary care. Previous research has looked at the reasons underlying recruitment and retention problems, but little research has looked at what works to improve recruitment and retention. The aim of this systematic review is to evaluate interventions and strategies used to recruit and retain primary care doctors internationally. Methods A systematic review was undertaken. MEDLINE, EMBASE, CENTRAL and grey literature were searched from inception to January 2015.Articles assessing interventions aimed at recruiting or retaining doctors in high income countries, applicable to primary care doctors were included. No restrictions on language or year of publication. The first author screened all titles and abstracts and a second author screened 20%. Data extraction was carried out by one author and checked by a second. Meta-analysis was not possible due to heterogeneity. Results 51 studies assessing 42 interventions were retrieved. Interventions were categorised into thirteen groups: financial incentives (n=11), recruiting rural students (n=6), international recruitment (n=4), rural or primary care focused undergraduate placements (n=3), rural or underserved postgraduate training (n=3), well-being or peer support initiatives (n=3), marketing (n=2), mixed interventions (n=5), support for professional development or research (n=5), retainer schemes (n=4), re-entry schemes (n=1), specialised recruiters or case managers (n=2) and delayed partnerships (n=2). Studies were of low methodological quality with no RCTs and only 15 studies with a comparison group. Weak evidence supported the use of postgraduate placements in underserved areas, undergraduate rural placements and recruiting students to medical school from rural areas. There was mixed evidence about financial incentives. A marketing campaign was associated with lower recruitment. Conclusions This is the first systematic review of interventions to improve recruitment and retention of primary care doctors. Although the evidence base for recruiting and care doctors is weak and more high quality research is needed, this review found evidence to support undergraduate and postgraduate placements in underserved areas, and selective recruitment of medical students. Other initiatives covered may have potential to improve recruitment and retention of primary care practitioners, but their effectiveness has not been established

Isolation and fine mapping of Rps6: An intermediate host resistance gene in barley to wheat stripe rust

A plant may be considered a nonhost of a pathogen if all known genotypes of a plant species are resistant to all known isolates of a pathogen species. However, if a small number of genotypes are susceptible to some known isolates of a pathogen species this plant maybe considered an intermediate host. Barley (Hordeum vulgare) is an intermediate host for Puccinia striiformis f. sp. tritici (Pst), the causal agent of wheat stripe rust. We wanted to understand the genetic architecture underlying resistance to Pst and to determine whether any overlap exists with resistance to the host pathogen, Puccinia striiformis f. sp. hordei (Psh). We mapped Pst resistance to chromosome 7H and show that host and intermediate host resistance is genetically uncoupled. Therefore, we designate this resistance locus Rps6. We used phenotypic and genotypic selection on F2:3 families to isolate Rps6 and fine mapped the locus to a 0.1 cM region. Anchoring of the Rps6 locus to the barley physical map placed the region on two adjacent fingerprinted contigs. Efforts are now underway to sequence the minimal tiling path and to delimit the physical region harbouring Rps6. This will facilitate additional marker development and permit identification of candidate genes in the region

Genetic, environmental and stochastic factors in monozygotic twin discordance with a focus on epigenetic differences

PMCID: PMC3566971This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

WordCluster: detecting clusters of DNA words and genomic elements

<p>Abstract</p> <p>Background</p> <p>Many <it>k-</it>mers (or DNA words) and genomic elements are known to be spatially clustered in the genome. Well established examples are the genes, TFBSs, CpG dinucleotides, microRNA genes and ultra-conserved non-coding regions. Currently, no algorithm exists to find these clusters in a statistically comprehensible way. The detection of clustering often relies on densities and sliding-window approaches or arbitrarily chosen distance thresholds.</p> <p>Results</p> <p>We introduce here an algorithm to detect clusters of DNA words (<it>k-</it>mers), or any other genomic element, based on the distance between consecutive copies and an assigned statistical significance. We implemented the method into a web server connected to a MySQL backend, which also determines the co-localization with gene annotations. We demonstrate the usefulness of this approach by detecting the clusters of CAG/CTG (cytosine contexts that can be methylated in undifferentiated cells), showing that the degree of methylation vary drastically between inside and outside of the clusters. As another example, we used <it>WordCluster </it>to search for statistically significant clusters of olfactory receptor (OR) genes in the human genome.</p> <p>Conclusions</p> <p><it>WordCluster </it>seems to predict biological meaningful clusters of DNA words (<it>k-</it>mers) and genomic entities. The implementation of the method into a web server is available at <url>http://bioinfo2.ugr.es/wordCluster/wordCluster.php</url> including additional features like the detection of co-localization with gene regions or the annotation enrichment tool for functional analysis of overlapped genes.</p

A symmoriiform chondrichthyan braincase and the origin of chimaeroid fishes

Chimaeroid fishes (Holocephali) are one of the four principal divisions of modern gnathostomes (jawed vertebrates). Despite only 47 described living species1, chimaeroids are the focus of resurgent interest as potential archives of genomic data2 and for the unique perspective they provide on chondrichthyan and gnathostome ancestral conditions. Chimaeroids are also noteworthy for their highly derived body plan1,3,4. However, like other living groups with distinctive anatomies5, fossils have been of limited use in unravelling their evolutionary origin, as the earliest recognized examples already exhibit many of the specializations present in modern forms6,7. Here we report the results of a computed tomography analysis of Dwykaselachus, an enigmatic chondrichthyan braincase from the ~280 million year old Karoo sediments of South Africa8. Externally, the braincase is that of a symmoriid shark9,10,11,12,13and is by far the most complete uncrushed example yet discovered. Internally, the morphology exhibits otherwise characteristically chimaeroid specializations, including the otic labyrinth arrangement and the brain space configuration relative to exceptionally large orbits. These results have important implications for our view of modern chondrichthyan origins, add robust structure to the phylogeny of early crown group gnathostomes, reveal preconditions that suggest an initial morpho-functional basis for the derived chimaeroid cranium, and shed new light on the chondrichthyan response to the extinction at the end of the Devonian period

Stochastic climate theory and modeling

Stochastic methods are a crucial area in contemporary climate research and are increasingly being used in comprehensive weather and climate prediction models as well as reduced order climate models. Stochastic methods are used as subgrid-scale parameterizations (SSPs) as well as for model error representation, uncertainty quantification, data assimilation, and ensemble prediction. The need to use stochastic approaches in weather and climate models arises because we still cannot resolve all necessary processes and scales in comprehensive numerical weather and climate prediction models. In many practical applications one is mainly interested in the largest and potentially predictable scales and not necessarily in the small and fast scales. For instance, reduced order models can simulate and predict large-scale modes. Statistical mechanics and dynamical systems theory suggest that in reduced order models the impact of unresolved degrees of freedom can be represented by suitable combinations of deterministic and stochastic components and non-Markovian (memory) terms. Stochastic approaches in numerical weather and climate prediction models also lead to the reduction of model biases. Hence, there is a clear need for systematic stochastic approaches in weather and climate modeling. In this review, we present evidence for stochastic effects in laboratory experiments. Then we provide an overview of stochastic climate theory from an applied mathematics perspective. We also survey the current use of stochastic methods in comprehensive weather and climate prediction models and show that stochastic parameterizations have the potential to remedy many of the current biases in these comprehensive models

Influence of advanced age of maternal grandmothers on Down syndrome

BACKGROUND: Down syndrome (DS) is the most common chromosomal anomaly associated with mental retardation. This is due to the occurrence of free trisomy 21 (92–95%), mosaic trisomy 21 (2–4%) and translocation (3–4%). Advanced maternal age is a well documented risk factor for maternal meiotic nondisjunction. In India three children with DS are born every hour and more DS children are given birth to by young age mothers than by advanced age mothers. Therefore, detailed analysis of the families with DS is needed to find out other possible causative factors for nondisjunction. METHODS: We investigated 69 families of cytogenetically confirmed DS children and constructed pedigrees of these families. We also studied 200 randomly selected families belonging to different religions as controls. Statistical analysis was carried out using logistic regression. RESULTS: Out of the 69 DS cases studied, 67 were free trisomy 21, two cases were mosaic trisomy 21 and there were none with translocation. The number of DS births was greater for the young age mothers compared with the advanced age mothers. It has also been recorded that young age mothers (18 to 29 years) born to their mothers at the age 30 years and above produced as high as 91.3% of children with DS. The logistic regression of case- control study of DS children revealed that the odds ratio of age of grandmother was significant when all the four variables were used once at a time. However, the effect of age of mother and father was smaller than the effect of age of maternal grandmother. Therefore, for every year of advancement of age of the maternal grandmother, the risk (odds) of birth of DS baby increases by 30%. CONCLUSION: Besides the known risk factors, mother's age, father's age, the age of the maternal grandmother at the time of birth of the mother is a risk factor for the occurrence of Down syndrome

Early members of ‘living fossil’ lineage imply later origin of modern ray-finned fishes

Modern ray-finned fishes (Actinopterygii) comprise half of extant vertebrate species and are widely thought to have originated before or near the end of the Middle Devonian epoch (around 385 million years ago). Polypterids (bichirs and ropefish) represent the earliest-diverging lineage of living actinopterygians, with almost all Palaeozoic taxa interpreted as more closely related to other extant actinopterygians than to polypterids. By contrast, the earliest material assigned to the polypterid lineage is mid-Cretaceous in age (around 100 million years old), implying a quarter-of-a-billion-year palaeontological gap. Here we show that scanilepiforms, a widely distributed radiation from the Triassic period (around 252–201 million years ago), are stem polypterids. Importantly, these fossils break the long polypterid branch and expose many supposedly primitive features of extant polypterids as reversals. This shifts numerous Palaeozoic ray-fins to the actinopterygian stem, reducing the minimum age for the crown lineage by roughly 45 million years. Recalibration of molecular clocks to exclude phylogenetically reassigned Palaeozoic taxa results in estimates that the actinopterygian crown lineage is about 20–40 million years younger than was indicated by previous molecular analyses. These new dates are broadly consistent with our revised palaeontological timescale and coincident with an interval of conspicuous morphological and taxonomic diversification among ray-fins centred on the Devonian–Carboniferous boundary. A shifting timescale, combined with ambiguity in the relationships of late Palaeozoic actinopterygians, highlights this part of the fossil record as a major frontier in understanding the evolutionary assembly of modern vertebrate diversity