Search

Single-cell RNA-Sequencing (scRNA-Seq) has undergone major technological advances in recent years, enabling the conception of various organism-level cell atlassing projects. With increasing numbers of datasets being deposited in public archives, there is a need to address the challenges of enabling the reproducibility of such data sets. Here, we describe guidelines for a minimum set of metadata to sufficiently describe scRNA-Seq experiments, ensuring reproducibility of data analyses.

Funder: MS is funded by Medical Research Council (MC-A652-5QA20), Funder: This work was supported by the Wellcome Trust grant (206194) and EU FP7 High Impact Project BLUEPRINT (HEALTH-F5-2011-282510), Neutrophils play fundamental roles in innate immune response, shape adaptive immunity, and are a potentially causal cell type underpinning genetic associations with immune system traits and diseases. Here, we profile the binding of myeloid master regulator PU.1 in primary neutrophils across nearly a hundred volunteers. We show that variants associated with differential PU.1 binding underlie genetically-driven differences in cell count and susceptibility to autoimmune and inflammatory diseases. We integrate these results with other multi-individual genomic readouts, revealing coordinated effects of PU.1 binding variants on the local chromatin state, enhancer-promoter contacts and downstream gene expression, and providing a functional interpretation for 27 genes underlying immune traits. Collectively, these results demonstrate the functional role of PU.1 and its target enhancers in neutrophil transcriptional control and immune disease susceptibility.

There is an association between latitude, relative vitamin D deficiency and risk of multiple sclerosis (MS), and an association between vitamin D and disease progression. We have performed a meta-analysis with the aim of investigating the role of therapeutic vitamin D in MS. A systematic search of databases was performed to identify clinical trials assessing vitamin D in patients with relapsing–remitting MS. Studies were selected based on inclusion and exclusion criteria. Analysis was performed using RevMan 5.3 software. Twelve studies involving 950 patients were included in the final analysis. Studies were divided into four groups because of heterogeneity in study design. Studies were judged to be at low or unclear risk of bias, except in three studies, and this was confirmed by funnel plots. No statistically significant difference was seen for any of the outcome measures. There were non-significant trends in favour of vitamin D for all outcome measures, particularly when only placebo-controlled studies were included. Dose comparison studies showed a significant increase in annualised relapse rate (mean difference 0.15 [95%CI 0.01–0.30]) and non-significant trends of increased Expanded Disability Status Scale and gadolinium-enhancing lesions for the higher-dose arms. These findings suggest that vitamin D supplementation may have a therapeutic role in the treatment of MS. However, there is uncertainty with regard to the most appropriate dose, with high doses potentially being associated with worse outcomes. There remains the need for further well-performed randomised, dose-ranging, placebo-controlled trials of vitamin D in MS.

SUMMARY Dopaminergic neurons in the ventral tegmental area (VTA) are well known for their role in mediating the positive reinforcing effects of drugs of abuse. Here, we identify in rodents and humans a population of VTA dopamine neurons co-expressing corticotropin releasing factor (CRF). We provide further evidence in rodents that chronic nicotine exposure upregulates CRF mRNA in dopaminergic neurons of the posterior VTA, activates local CRF1 receptors, and blocks nicotine-induced activation of transient GABAergic input to dopaminergic neurons. Local downregulation of CRF mRNA and specific pharmacological blockade of CRF1 receptors in the VTA reversed the effect of nicotine on GABAergic input to dopaminergic neurons, prevented the aversive effects of nicotine withdrawal, and limited the escalation of nicotine intake. These results link the brain reward and stress systems within the same brain region in signaling the negative motivational effects of nicotine withdrawal.

This paper reports on findings from a qualitative interview-based study of women’s experiences and perceptions of menstrual suppression using a diverse sample of 12 women from Vancouver, Canada. The study used open-ended, in-depth interviews to ask women questions related to the following overarching research question: How do Canadian women perceive and experience menstrual suppression? Of the 12 women, six had experience with menstrual suppression, while six had never suppressed their periods. The six women who suppressed their periods cited convenience, pain management, and feeling more positively about their bodies as their reasons for suppression. The six women who had not suppressed their cycles cited fears about compromising their health, worries about altering the “natural” menstrual cycle, and an uneasiness with pharmaceutical products in general as rationales for rejecting menstrual suppression. Ultimately, the findings reveal that there are many considerations and factors involved in women’s decisions about menstrual frequency. While many of the women appreciated the appeal of menstrual suppression, the long-term risks and health uncertainties deterred many of them from reducing their menstrual frequency. The findings are discussed in relation to medical literature which encourages women to suppress their menses, as well as sociological theorizing about menstrual culture within a Foucauldian framework of discipline and control.

Nature 546, 370–375 (2017); doi:10.1038/nature22403 In this Article, the authors Fiona M. Watt and Richard Durbin should also have been included as ‘jointly supervising’ authors, and authors Oliver Stegle and Daniel J. Gaffney should also have been noted as ‘equally contributing’ authors. In addition, the Author Contributions section should have included the sentence: ‘H.K. and A.G. contributed equally to this work; O.S. and D.J.G. contributed equally to this work’, as further clarification. The original Article has been corrected online.

J.B.S. Haldane proposed in 1947 that the male germline may be more mutagenic than the female germline. Diverse studies have supported Haldane's contention of a higher average mutation rate in the male germline in a variety of mammals, including humans. Here we present, to our knowledge, the first direct comparative analysis of male and female germline mutation rates from the complete genome sequences of two parent-offspring trios. Through extensive validation, we identified 49 and 35 germline de novo mutations (DNMs) in two trio offspring, as well as 1,586 non-germline DNMs arising either somatically or in the cell lines from which the DNA was derived. Most strikingly, in one family, we observed that 92% of germline DNMs were from the paternal germline, whereas, in contrast, in the other family, 64% of DNMs were from the maternal germline. These observations suggest considerable variation in mutation rates within and between families.

A wet chemical approach to preparing one- and two-dimensional arrays of gold nanoparticles assembled onto a polypeptide (poly-L-lysine) scaffold layer is reported. The electrical properties of biopolymer templated and nontemplated gold nanoparticle samples are compared. The electrical response of nontemplated samples is unstable, likely due to nanoparticle mobility. Biopolymer templating provides a simple, chemical method to immobilize the particles and is found to stabilize the electrical response (Coulomb blockade) of the array. A striking feature of the electrical properties is that the electron transport properties are dominated by transport through one-dimensional chains within the sample. Structural studies by AFM and XPS support the transport findings and provide evidence for the formation of one-dimensional assemblies within the arrays.

Nature 453, 175–183 (2008) In this Article, Mikhail Nefedov and Pieter J. de Jong were omitted from the author list.