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Inborn errors of the alternative NF-κB pathway in humans impair the development of AIRE-expressing medullary thymic epithelial cells, thereby underlying the production of autoantibodies against type I IFNs and predisposition to viral diseases

Barley plants coat their organs with waxy diketones to protect against late-summer droughts. These diketones are formed by two enzymes, one diverting common fatty acids from normal metabolism and the other one linking two fatty acid units together.

The energy potentials created by laser light can trap atoms. An analogous effect that traps electrons in solid-state systems is now proposed. The electron traps are created in quantum wells and wires in the presence of quasiparticles composed of two electrons and a hole. The idea could lead to advances in ultrafast optical and new optoelectronic devices.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Accumulation of intermediates of haem biosynthesis, porphyrins, is harmful and usually inherited, but it is unclear how the same mutation may make some individuals more ill than others. Here, the authors show that a porphyrin transporter ABCB6 is a modulator of porphyria, and that patients with functionally defective ABCB6 show more severe symptoms.

Exome sequencing within a structured diagnostic process for rare diseases in Germany shows how facial image analysis and machine learning can guide variant prioritization and uncover many ultrarare diseases.

The main function of the mammary gland is to produce milk to sustain offspring. Here, the authors show that secretory alveolar cells in the lactating gland in several species are binucleated, which increases milk production, and that binucleation is regulated by Aurora kinase-A and Polo-like kinase-1.

ICER is a CREM splice variant that represses CREM/CREB signalling. Here the authors use human cells and mouse models of various autoimmune diseases to show that ICER is central to pathogenic Th17 cell differentiation in autoimmunity.

Combinatorial optimization, the search for the minimum of an objective function within a finite but very large set of candidate solutions, finds many important and challenging applications in science and industry. A new graph neural network deep learning approach that incorporates concepts from statistical physics is used to develop a robust solver that can tackle a large class of NP-hard combinatorial optimization problems.

Visvader and colleagues report that in the mouse mammary gland, EGF and mTOR signalling induce expression of the anti-apoptotic Bcl2 family member Mcl-1 and show that this is required for the survival of milk-producing mammary epithelial cells.

It remains unclear whether exotic and native species are functionally different. Using a global grassland experiment, Seabloomet al. show that native and exotic species respond differently to two globally pervasive environmental changes, addition of mineral nutrients and alteration of herbivore density.

Human mutations in PCYT2 result in severe pathology with failure to thrive and progressive degenerative disease. Cikes et al. demonstrate that loss of PCYT2-synthesized phosphatidylethanolamines in muscle impairs sarcolemmal lipid bilayer stability and mitochondrial homeostasis, leading to muscle degeneration and premature ageing in mice.

The mechanisms underlying perinatal mortality due to intrahepatic cholestasis of pregnancy are not fully understood. Here, the authors show that absence of the nuclear receptor and bile acid regulator Nrli2 and the biliary transporter Abcb11 strongly reduces maternal serum bile acid levels, improving neonatal survival.

CX-5461 recently progressed through phase I clinical trial as a first-inhuman inhibitor of RNA-POL I. Here, the authors demonstrate that CX-5461 synergizes with topoisomerase I inhibitors to inhibit neuroblastoma cells and that its primary target in this disease is topoisomerase II beta and not RNA-POL I.

Here, using longitudinal pre- and post-infection samples from the RV217 Early Capture HIV Cohort Study, the authors show that mucosa-associated invariant T (MAIT) cells become activated and expand during the early acute phase of HIV infection, with subsequent reprogramming towards innate-like functionality.

Small intestinal bacterial overgrowth (SIBO) has been associated with functional gastrointestinal disorders. Here, the authors show that SIBO may be a result of dietary preferences, and patient symptoms correlate with changes in small intestinal microbial composition but not with SIBO.

Water is an important component of collagen in tendons, bone and extracellular matrix, but its role in the mechanical function of protein is poorly understood. Here, the authors study the effects of osmotic pressure on contraction in collagen, suggesting that collagen could function as a mechanical actuator.

Researchers use sideband injection-locked lasers to generate low-noise, high-frequency radio signals that can be tuned over the range of 0.5–110 GHz. This technique is amenable to compact integration and, in principle, operation at even higher frequencies.

Analysis of 65 grasslands worldwide from the Nutrient Network experiment reveals that plant communities with higher α- and β-diversity have higher levels of ecosystem multifunctionality, and that this effect is amplified across scales.

Mechanical forces acting on ligand-engaged T-cell receptors (TCRs) have previously been implicated in T-cell antigen recognition, yet their sensitivity and specificity are still poorly defined. Here, authors report a FRET-based sensor that informs directly on the magnitude and kinetics of TCR-imposed forces at the single molecule level.

MCL-1 is an anti-apoptotic BCL-2 family member and is frequently upregulated in cancer, but the mechanism by which it promotes cell survival has been elusive. Opferman and colleagues provide insight into this process by showing that MCL-1 exists in different forms with discrete localizations and functions. MCL-1 variants targeted to the outer mitochondrial membrane antagonize BAX and BAK activation, whereas an N-terminally truncated isoform localizes to the mitochondrial matrix and regulates mitochondrial metabolism.

TCRs are often thought to be pre-clustered before T cell activation. Rossboth et al. use super-resolution microscopy and statistical image analysis to demonstrate that TCRs are in fact randomly distributed on resting T cells.

Co-patterning of a membrane protein bait and a fluorescently labeled prey is used to examine protein-protein interactions in a semiautomated fashion in living cells. Photobleaching experiments and single-molecule imaging further allow dynamic studies of the interaction.