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Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

Optogenetic applications would benefit from channelrhodopsins (ChRs) with faster photostimulation, increased tissue transparency and lower phototoxicity. Here, the authors develop fast red-shifted ChR variants and show the abilities for temporal precise spiking of cerebral interneurons and restoring auditory activity in deaf mice.

In Drosophila, ensheathing glia encase the neuropil but their function is not well understood. Here the authors show a surprising role of ensheathing glia in regulating glutamate homeostasis and locomotion which is controlled by the sulfite oxidase Shopper.

Mate preference and copulatory behavior in female rodents are coordinated with the ovulation cycles of the animal. This study shows that hypothalamic kisspeptin neurons control both mate choice and copulation, and therefore, that sexual behavior and ovulation may be synchronized by the same neuropeptide.

In this study, the authors show that they can induce the direct conversion of fibroblasts into nociceptor neurons via the expression of only five key transcription factors. They further confirm that these induced neurons are bona fide nociceptors by demonstrating that their expression profiles resemble that of their endogenous counterparts and show that they are responsive to common nociceptor agonists.

iTango confers access to neuromodulation-sensitive subsets of neurons in a functionally defined and temporally controlled manner. The tool allows for manipulating the subset of neurons that are activated by dopamine during a behavior of interest.

A collection of improved FRET-based calcium biosensors, called Twitch sensors, is described. Twitches have a reduced number of calcium binding sites per sensor and display high sensitivity in in vivo imaging experiments in mouse brain and lymph node.

Two screening approaches converge on capzimin, a first-in-class inhibitor of the Rpn11 protease component of the 19S proteasome. Capzimin stabilizes polyubiquitinated substrates, induces the unfolded protein response, and blocks proliferation of cancer cells.

Over 170 susceptibility loci have been identified by genome-wide association studies in breast cancer. Here, the authors interrogated the role of risk-associated variants from non-breast tissue, and using expression quantitative trait loci, identify potential target genes of known breast cancer susceptibility variants, as well as 11 regions not previously known to be associated with breast cancer risk.

Roger Milne and colleagues conduct a genome-wide association study for estrogen receptor (ER)-negative breast cancer combined with BRCA1 mutation carriers in a large cohort. They identify ten new risk variants and find high genetic correlation between breast cancer risk for BRCA1 mutation carriers and risk of ER-negative breast cancer in the general population.

In a clinical trial, Fathi et al. show that a booster vaccination with a vector vaccine candidate against the highly pathogenic Middle East Respiratory Syndrome coronavirus is safe and strongly improves the immunity generated by primary immunization.

Genome-wide association analyses identify new susceptibility loci for Brugada syndrome. Functional studies implicate microtubule-related trafficking effects on sodium channel expression as an underlying molecular mechanism.

Integration of GWAS and single-cell transcriptomic data from the entire nervous system systematically identifies cell types underlying brain complex traits and provides insights into the etiology of Parkinson’s disease.

Guglielmetti et al. show the potential for monitoring response to immunomodulatory treatment in a model of multiple sclerosis using hyperpolarized ¹³C metabolic MRI. The authors observe reduced pyruvate-to-lactate flux in vivo after treatment with fingolimod or dimethyl fumarate, as well as changes in immune cell populations.

This protocol describes the design, in vitro characterization, and imaging applications of iGluSnFR-based genetically encoded glutamate indicators (GEGIs) in tissue culture of rat hippocampus.

Georgia Chenevix-Trench and colleagues report meta-analyses of genome-wide association studies identifying six loci newly associated with epithelial ovarian cancer (EOC). They also test variants at the 12 known and 6 new EOC susceptibility loci for association in BRCA1 and BRCA2 mutation carriers.

Aarno Palotie and colleagues present results of a large genome-wide association study of migraine. They identified significant associations at 38 distinct loci and found enrichment for genes expressed in vascular and smooth muscle tissues.

Histone H4 is released from neutrophil extracellular traps and induces membrane lysis in vascular smooth muscle cells, leading to the destabilization of atherosclerotic plaques.

The photoactive properties of microalgae are well documented when it comes to photosynthesis and motility. But it seems their adhesion to surfaces can also be manipulated with light, which may serve to optimize their photoactive functionality.

Doug Easton and colleagues report the results of a large-scale genome-wide association study of breast cancer. They discover 15 new susceptibility loci and highlight likely target genes in several of the newly associated regions.

In vitro models mimicking in-patient conditions have the potential to yield exciting opportunities for antibiotic research and revitalize future antibiotic discovery and development.

BRET-based biosensors allow the quantitative live-cell monitoring of RTKmediated signaling, revealing ligand-specific spatiotemporal and mutation-specific signaling biases, advancing the understanding of RTK functional selectivity.

Fergus Couch and colleagues report a genome-wide association study for modifiers of breast cancer susceptibility in BRCA1 mutation carriers. They identify a locus at 19p13 associated with breast cancer risk in BRCA1 mutation carriers, and further replication studies identify this locus as associated with estrogen receptor–negative breast cancer in the general population.

FRET and confocal patch-clamp fluorometry in oocytes is used to analyze glutamateinduced conformational changes and dimerization of mGluR 1-8 homo- and heterodimers.

The authors present a sensitive and rapid method to determine the binding strength of MHC class 1 peptide complexes using native mass spectrometry.

Interactions between opposite subunits of HCN channels are relevant for stabilizing the auto-inhibited state of the channel. Like cAMP-binding, K464E-mutation breaks these interactions to favor a channel’s pre-activated state.