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Hypothalamic AgRP neurons are shown to control peripheral and central levels of lysophospholipids in association with food deprivation, which leads to cortical excitability, hyperphagia and body weight gain.

The authors report TNFα-dependent hyperactivity in cortical microcircuits during remission in a mouse model of multiple sclerosis, a maladaptive response to the immune attack with behavioral changes.

Synthesizing the cellular proteome is demanding and finely regulated. Here, the authors show that mTORC1 cooperates with tRNA wobble modification to promote ribosomal protein synthesis, thus supporting the high translational demands of cell growth.

Plasma extracellular vesicles contain quantifiable amounts of TDP-43 and full-length tau, allowing the accurate assessment of pathology in frontotemporal dementia, frontotemporal dementia spectrum disorders and amyotrophic lateral sclerosis.

Massively parallel but cost-effective testing is essential to monitor the spread of pathogenic agents. Here the authors present SARSseq, which uses a dual indexing strategy in a multiplexed RT-PCR reaction to diagnose SARS-CoV-2 at scale.

BehaviorFlow is a behavioral analysis package that overcomes challenges with multiple testing when dealing with large numbers of behavioral variables and limited availability of data. BehaviorFlow also allows combining datasets from different experiments.

Although γδ T cells are known to participate in immune dysregulation in solid tumors, their relevance to human microsatellite-stable (MSS) colorectal cancer (CRC) is less well-studied. Here, using single-cell RNA-sequencing, the authors identify a Vδ1 + T cell subset, which are functionally impaired in MSS CRC via a TIGIT-NECTIN2 interaction.

Generating training data for training deep-learning-based tools is time consuming. The DELiVR pipeline facilitates this process as demonstrated in this study on detecting c-Fos⁺ cells or microglia in the brain, following tissue clearing and imaging with light-sheet microscopy.

Changes in dielectric constant due to intimate mixing of thiophene molecules with different gaps between ionization energy and electron affinity induce gap variations at the single-particle level, finely tunable by controlling the mixture ratio.

A combination of gentle stimulated emission depletion microscopy imaging and deep-learning-based improvements in signal-to-noise ratio enables high-resolution reconstruction of neuronal architecture in living tissue.

Johannes Lemke, Holger Lerche and colleagues report the identification of de novo mutations in the potassium channel gene KCNA2 in patients with epileptic encephalopathies. The authors confirm in vitro that two mutations cause dominant loss of channel function, whereas the other two mutations induce gain-of-function effects, leading to permanently open channels.

Defect in the death receptor signally caused by impaired FADD/BID expression leads to failure of T-cell mediated immunotherapy in multiple myeloma patients.

In this work, Danileviciute, Zeng et al. provide new insights into the regulation of the PDH complex by PARK7/DJ-1 and show its relevance in T_reg homeostasis during ageing.

Land use intensification is a major driver of biodiversity change. Here the authors measure diversity across multiple trophic levels in agricultural grassland landscapes of varying management, finding decoupled responses of above- and belowground taxa to local factors and a strong impact of landscape-level land use.

VesSAP is a tissue clearing- and deep learning-based pipeline for comprehensively analyzing mouse vasculature, from large vessels to small capillaries.

This work identifies a population of precursors in the outer subventricular zone (SVZ) of developing human and ferret brains. The cells share some properties with the radial glia of the ventricular zone, and, in contrast with previously identified progenitors in SVZ, undergo several asymmetric neurogenic divisions. These progenitors may contribute to the development of gyrated cortices in higher mammals.

Red and green genetically encoded indicators for norepinephrine have been developed and employed to monitor norepinephrine during locomotion and reward behavior in mice. The strategy used for generating these indicators also produced indicators for other neuromodulators.

FIOLA is a pipeline for processing calcium or voltage imaging data. Its advantages include the fast speed and online processing.

Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by aggregation of Tau, encoded by MAPT. Here, the authors perform an EWAS for PSP in prefrontal lobe tissue and find hypermethylation of DLX1 and its antisense transcript DLX1AS to associate with MAPT expression.

Tropical cyclone winds intensify with warming but the impacts depend on global population, which is likely to peak by mid-century and then decline. Impact modelling suggests that stronger mitigation, under which warming would peak after the population begins to decline, may spare 1.8 billion people from impacts by 2100.

Chromodomain Helicase DNA-binding (CHD) proteins have been implicated in neurodevelopmental processes. Here, the authors identify missense variants in CHD3 that disturb its chromatin remodeling activities and cause a neurodevelopmental disorder with macrocephaly and speech and language impairment.

The introduction of metal sites into polyoxometalates is key for tuning their structure and reactivity but the complex mechanisms which govern metal functionalization of polyoxometalates are still poorly understood. Here, the authors report a coupled set of light-dependent and light-independent reaction equilibria controlling the mono- and di- metal-functionalization of a prototype molecular vanadium oxide cluster

BNT162b1 and BNT162b2 are two candidate mRNA vaccines against COVID-19 that elicit high virus-entry inhibition titres in mice, elicit high virus-neutralizing titres in rhesus macaques and protect macaques from SARS-CoV-2 challenge.

The authors developed small-molecule inhibitors of STOML3 oligomerization, a membrane protein that interacts with mechanosensitive ion channels, such as Piezo2. One of these molecules was effective in silencing touch receptors and reversed touch-evoked pain associated with nerve injury or diabetic neuropathy.

To achieve net-zero carbon emissions, we must close the carbon cycle for industries that are difficult to electrify. Developing the needed science to provide carbon alternatives and non-fossil carbon will accelerate advances towards defossilization.

Christel Depienne, Eric LeGuern and colleagues report the identification of 5 de novo missense mutations in HCN1 in individuals with early-onset epileptic encephalopathy. Functional studies confirmed the pathogenic nature of these mutations.

Variation in the promoter of the gene encoding uromodulin, the most abundant protein in urine, affects the individual risk of developing hypertension or chronic kidney disease. Luca Rampoldi, Olivier Devuyst and their colleagues show that the uromodulin risk alleles are associated with higher levels of uromodulin expression. This can promote hypertension, by stimulating sodium reabsorption by the loop of Henle in the kidney, and kidney damage in both mice and humans.