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BmrR is a member of the bacterial MerR transcription factor family that regulates the expression of the bacterial efflux pump Bmr. Here, the authors present the cryo-EM structure of a B. subtilis transcription activation complex (TAC) containing the RNA Polymerase (RNAP) core enzyme, σA, promoter DNA and ligand-bound BmrR, which reveals that in contrast to most other transcription factors BmrR does not directly interact with RNAP and instead activates transcription by modulating the shape of the core promoter.
Inhibition of the metabolic enzyme ATP-citrate lyase can attenuate atherosclerosis by preventing dyslipidemia and potentially also by reducing macrophage-mediated inflammation. Here, the authors show that specific targeting of ACLY in macrophages results in more stable atherosclerotic plaques.
Hypothalamic melanocortin neurons regulate systemic glucose homeostasis through incompletely understood pathways. Here, the authors show that a subset of pro-opiomelanocortin neurons innervate the liver via preganglionic parasympathetic cholinergic neurons in the dorsal motor nucleus of the vagus and that stimulation of this pathway elevates blood glucose levels
Large-scale meat production can have negative impacts on public health, the environment and animal welfare. In this Review, the authors consider plant-based and cell-based approaches to meat production and the challenges they face.
A new donkey reference genome and comparisons with wild asses yields insights into the evolutionary history of donkey domestication and identifies a genetic variant that results in the non-Dun coat colours of domestic donkeys.
White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.
Predicting the structure of unknown materials’ compositions represents a challenge for high-throughput computational approaches. Here the authors introduce a new stoichiometry-based machine learning approach for predicting the properties of inorganic materials from their elemental compositions.
Strong transgene suppression has been observed in Chlamydomonas reinhardtii, but the underlying mechanism is unknown. Here, the authors identify a sirtuin-type histone deacetylase that selectively acts on transgenic DNA to repress gene expression by assembling a repressive chromatin structure composed of deacetylated histones.
Mapping and quantifying degree of forest modification is critical to conserve and manage forests. Here the authors propose a new quantitative metric for landscape integrity and apply it to a global forest map, showing that less than half of the world’s forest cover has high integrity, most of which is outside nationally designed protected areas.
Identifying factors that enable cells to induce a potent stress response to amyloid-like aggregation can provide further insight into the mechanism of stress regulation. Here, the authors express polyglutamine-expanded Huntingtin as a model disease protein in yeast cells and perform a genetic screen for chaperone factors that allow yeast cells to activate a potent stress response. They identify Sis1, an essential Hsp40 co-chaperone of Hsp70, as a critical sensor of proteotoxic stress and further show that both Sis1 and its mammalian homolog DnaJB6 regulate the magnitude of the cellular heat stress response, indicating that this mechanism is conserved.
Epigenetic regulations of autophagy have emerged as mechanisms for maintaining cellular homeostasis. Here the authors reveal that the CARM1-Pontin-FOXO3a signaling axis can activate autophagy related genes through enhancer activation.
Muscle fibers are the largest cells in the body and contain less DNA per unit volume than other cells even if they have multiple nuclei. Here, the authors show that the number of nuclei regulates the cell size with similar scaling properties in mice and humans.
Female honeybee larvae develop into queens when they are fed exclusively with royal jelly (RJ) and major royal jelly protein 1 (MRJP1) is the main protein component of RJ. Here, the authors present the 3.5 Å cryo-EM structure of native RJ filament, where MRJP1 forms the outer shell surrounding apisimin tetramers with bound lipids at the core of the filament.
Hutchinson-Gilford progeria syndrome is a genetic disease where an aberrant form of Lamin A disrupts chromatin by interfering with lamina associated domains. Here, the authors present the SAMMY-seq, a method for genome-wide characterization of heterochromatin dynamics and detect early stage alterations of heterochromatin structure in progeria primary fibroblasts, accompained by Polycomb dysfunctions.
Dynamic labeling and tracking of organelle–organelle contacts is essential to understand the formation and function of these interactions. Here the authors present a small molecule probe, Coupa, that labels mitochondria and lysosomes with blue and red fluorescence, respectively.
Structured RNA motifs can be obtained by structure probing, duplex capture, and motif prediction. Here the authors develop a multiplexed affinity assay system to identify functional protein interactors from an RNA structure library with validated or predicted RNA motifs.
Ovarian cancer cells often metastasize to the peritoneal cavity, forming spheroid-like structures and promoting a highly immunosuppressive tumor microenvironment. Here, the authors show that the ubiquitin ligase UBR5 is required for ovarian cancer growth and metastasis, sustaining spheroid formation and the infiltration of immunosuppressive tumor associated macrophages.
The in vivo firing patterns of ventral midbrain dopamine neurons are controlled by afferent and intrinsic activity. The authors identified biophysical membrane potential signatures associated with distinct in vivo firing patterns in whole-cell recordings of spontaneously active midbrain dopamine neurons.
Climate change and local anthropogenic stressors threaten the persistence of coral reefs. Here the authors track coral bleaching over the course of a heatwave and find that some colonies recovered from bleaching while high temperatures persisted, but only at sites lacking in other strong anthropogenic stressors.
It has been reported that several phytohormones are involved in the regulation of grain weight, but the role of jasmonic acids (JA) remains elusive. Here, via bulked segregant analysis (BSA)-based cloning, the authors show keto-acyl thiolase 2B involved in β-oxidation during JA synthesis is a positive regulator of wheat grain weight.