Recovery of gene haplotypes from a metagenome

AbstractElucidation of population-level diversity of microbiomes is a significant step towards a complete understanding of the evolutionary, ecological and functional importance of microbial communities. Characterizing this diversity requires the recovery of the exact DNA sequence (haplotype) of each gene isoform from every individual present in the community. To address this, we present Hansel and Gretel: a freely-available data structure and algorithm, providing a software package that reconstructs the most likely haplotypes from metagenomes. We demonstrate recovery of haplotypes from short-read Illumina data for a bovine rumen microbiome, and verify our predictions are 100% accurate with long-read PacBio CCS sequencing. We show that Gretel’s haplotypes can be analyzed to determine a significant difference in mutation rates between core and accessory gene families in an ovine rumen microbiome. All tools, documentation and data for evaluation are open source and available via our repository: https://github.com/samstudio8/gretel</jats:p

Provision of cervical screening for transmasculine patients: a review of clinical and programmatic guidelines.

BACKGROUND: Most cervical cancer can be prevented through routine screening. Disparities in uptake of routine screening therefore translate into disparities in cervical cancer incidence and outcomes. Transmasculine people including transgender men experience multiple barriers to cervical screening and their uptake of screening is low compared with cisgender women. Comprehensive evidence-based guidelines are needed to improve cervical screening for this group. METHODS: We searched for and synthesised clinical and programmatic guidelines for the provision of cervical screening for transmasculine patients. FINDINGS: The guidelines offer recommendations addressing: (1) reception, check-in and clinic facilities; (2) patient data and invitation to screening; (3) improving inclusion in screening programmes; and (4) sexual history taking, language and identity. Guidelines offer strategies for alleviating physical and psychological discomfort during cervical screening and recommendations on what to do if the screening procedure cannot be completed. Most of the guidelines were from and for high-income countries. DISCUSSION: The evidence base is limited, but existing guidelines provide recommendations to ensure life-saving screening services are available to all who need them. We were only able to identify one set of guidelines for a middle-income country, and none for low-income countries. We encourage the involvement of transmasculine people in the development of future guidelines

Weather Variability, Tides, and Barmah Forest Virus Disease in the Gladstone Region, Australia

In this study we examined the impact of weather variability and tides on the transmission of Barmah Forest virus (BFV) disease and developed a weather-based forecasting model for BFV disease in the Gladstone region, Australia. We used seasonal autoregressive integrated moving-average (SARIMA) models to determine the contribution of weather variables to BFV transmission after the time-series data of response and explanatory variables were made stationary through seasonal differencing. We obtained data on the monthly counts of BFV cases, weather variables (e.g., mean minimum and maximum temperature, total rainfall, and mean relative humidity), high and low tides, and the population size in the Gladstone region between January 1992 and December 2001 from the Queensland Department of Health, Australian Bureau of Meteorology, Queensland Department of Transport, and Australian Bureau of Statistics, respectively. The SARIMA model shows that the 5-month moving average of minimum temperature (β = 0.15, p-value < 0.001) was statistically significantly and positively associated with BFV disease, whereas high tide in the current month (β = −1.03, p-value = 0.04) was statistically significantly and inversely associated with it. However, no significant association was found for other variables. These results may be applied to forecast the occurrence of BFV disease and to use public health resources in BFV control and prevention

A Scoping Study To Explore The Application And Impact Of Grading Practice In Pre-registration Midwifery Programmes Across The United Kingdom.

Grading of practice is a mandatory element of programmes leading to registration as a midwife in the United Kingdom, required by the Nursing and Midwifery Council. This validates the importance of practice by placing it on an equal level with academic work, contributing to degree classification. This paper discusses a scoping project undertaken by the Lead Midwives for Education group across the 55 Higher Education Institutions in the United Kingdom which deliver pre-registration midwifery programmes. A questionnaire was circulated and practice tools shared, enabling exploration of the application of the standards and collation of the views of the Lead Midwives. Timing and individuals involved in practice assessment varied as did the components and the credit weighting applied to practice modules. Sign-off mentor confidence in awarding a range of grades had increased over time, and mentors seemed positive about the value given to practice and their role as professional gatekeepers. Grading was generally felt to be more robust and meaningful than pass/refer. It also appeared that practice grading may contribute to an enhanced student academic profile. A set of guiding principles is being developed with the purpose of enhancing consistency of the application of the professional standards across the United Kingdom

Generation and transmission of interlineage recombinants in the SARS-CoV-2 pandemic.

We present evidence for multiple independent origins of recombinant SARS-CoV-2 viruses sampled from late 2020 and early 2021 in the United Kingdom. Their genomes carry single-nucleotide polymorphisms and deletions that are characteristic of the B.1.1.7 variant of concern but lack the full complement of lineage-defining mutations. Instead, the remainder of their genomes share contiguous genetic variation with non-B.1.1.7 viruses circulating in the same geographic area at the same time as the recombinants. In four instances, there was evidence for onward transmission of a recombinant-origin virus, including one transmission cluster of 45 sequenced cases over the course of 2 months. The inferred genomic locations of recombination breakpoints suggest that every community-transmitted recombinant virus inherited its spike region from a B.1.1.7 parental virus, consistent with a transmission advantage for B.1.1.7's set of mutations.The COG-UK Consortium is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) (MC_PC_19027), and Genome Research Limited, operating as the Wellcome Sanger Institute. O.G.P. was supported by the Oxford Martin School. J.T.M., R.M.C., N.J.L., and A.R. acknowledge the support of the Wellcome Trust (Collaborators Award 206298/Z/17/Z – ARTIC network). D.L.R. acknowledges the support of the MRC (MC_UU_12014/12) and the Wellcome Trust (220977/Z/20/Z). E.S. and A.R. are supported by the European Research Council (grant agreement no. 725422 – ReservoirDOCS). T.R.C. and N.J.L. acknowledge the support of the MRC, which provided the funding for the MRC CLIMB infrastructure used to analyze, store, and share the UK sequencing dataset (MR/L015080/1 and MR/T030062/1). The samples sequenced in Wales were sequenced partly using funding provided by the Welsh Government

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Holocene break-up and reestablishment of the Petermann Ice Tongue, Northwest Greenland

Over the last decade, two major calving events of the Petermann Ice Tongue in Northwest Greenland have led to speculation on its future stability and contribution to further Greenland Ice Sheet mass loss. However, it has been unclear if these events are anomalous or typical within the context of limited historical observations. We extend the historical record of the floating ice tongue using the stratigraphy of Petermann Fjord sediments to provide a longer-term perspective. Computed tomography (CT) scans, X-Ray Fluorescence (XRF) scans, Ice-Rafted Debris (IRD) counts, and the magnetic properties of specific particle size fractions constrain changes in depositional processes and sediment sources at our core sites, allowing for reconstructions of past behavior of the Petermann Ice Tongue. Radiocarbon dating of foraminifera, 210Pb, and paleomagnetic secular variation (PSV) provide age control and help to address uncertainties in radiocarbon reservoir ages. A floating ice tongue in Petermann Fjord formed in late glacial time as Petermann Glacier retreated from an advanced grounded position. This paleo-ice tongue broke-up during the early Holocene when high northern latitude summer insolation was higher than present. After gradual regrowth of the ice tongue associated with regional cooling, the ice tongue reached its historical extent only within the last millennium. Little or no ice tongue was present for nearly 5000 years during the middle Holocene, when decadal mean regional temperatures are estimated to be 0.8e2.9 °C higher than preindustrial (1750 CE) and seasonal sea-ice in the Lincoln Sea was reduced. This pre-historical behavior shows that recent anthropogenic warming may already be in the range of ice tongue instability and future projected warming increases the risk of ice tongue break-up by the mid- 21st Century

Climate change, malaria and neglected tropical diseases: a scoping review

To explore the effects of climate change on malaria and 20 neglected tropical diseases (NTDs), and potential effect amelioration through mitigation and adaptation, we searched for papers published from January 2010 to October 2023. We descriptively synthesised extracted data. We analysed numbers of papers meeting our inclusion criteria by country and national disease burden, healthcare access and quality index (HAQI), as well as by climate vulnerability score. From 42 693 retrieved records, 1543 full-text papers were assessed. Of 511 papers meeting the inclusion criteria, 185 studied malaria, 181 dengue and chikungunya and 53 leishmaniasis; other NTDs were relatively understudied. Mitigation was considered in 174 papers (34%) and adaption strategies in 24 (5%). Amplitude and direction of effects of climate change on malaria and NTDs are likely to vary by disease and location, be non-linear and evolve over time. Available analyses do not allow confident prediction of the overall global impact of climate change on these diseases. For dengue and chikungunya and the group of non-vector-borne NTDs, the literature privileged consideration of current low-burden countries with a high HAQI. No leishmaniasis papers considered outcomes in East Africa. Comprehensive, collaborative and standardised modelling efforts are needed to better understand how climate change will directly and indirectly affect malaria and NTDs

Monoallelic Expression of Multiple Genes in the CNS

The inheritance pattern of a number of major genetic disorders suggests the possible involvement of genes that are expressed from one allele and silent on the other, but such genes are difficult to detect. Since DNA methylation in regulatory regions is often a mark of gene silencing, we modified existing microarray-based assays to detect both methylated and unmethylated DNA sequences in the same sample, a variation we term the MAUD assay. We probed a 65 Mb region of mouse Chr 7 for gene-associated sequences that show two distinct DNA methylation patterns in the mouse CNS. Selected genes were then tested for allele-specific expression in clonal neural stem cell lines derived from reciprocal F1 (C57BL/6×JF1) hybrid mice. In addition, using a separate approach, we directly analyzed allele-specific expression of a group of genes interspersed within clusters of OlfR genes, since the latter are subject to allelic exclusion. Altogether, of the 500 known genes in the chromosomal region surveyed, five show monoallelic expression, four identified by the MAUD assay (Agc1, p (pink-eyed dilution), P4ha3 and Thrsp), and one by its proximity to OlfR genes (Trim12). Thrsp (thyroid hormone responsive SPOT14 homolog) is expressed in hippocampus, but the human protein homolog, S14, has also been implicated in aggressive breast cancer. Monoallelic expression of the five genes is not coordinated at a chromosome-wide level, but rather regulated at individual loci. Taken together, our results suggest that at least 1% of previously untested genes are subject to allelic exclusion, and demonstrate a dual approach to expedite their identification