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Nonninger et al. identify the TFEB–TGFβ signaling axis as a regulator of stem cell resilience that protects against a senescence-like state during the adult diapause in Caenorhabditis elegans, a mechanism conserved in vertebrate aging and mammalian cancer.

Military personnel face increased exposure to pandemic-related stressors, yet their mental health impacts remain underexplored. Here, the authors analyze data from the STARRS Longitudinal Study, revealing significant increases in mental health issues among soldiers during COVID-19, particularly among vulnerable groups, underscoring the need for targeted support during pandemics.

Nixon-Abell et al. show that ANXA11 condensation on lysosomal membranes causes a coupled phase transition of the underlying lipids and mechanical stiffening of the overall ensemble involved in RNP granule-lysosome tethering and co-trafficking.

Identifying an immunologic marker as a correlate of protection (CoP) for RSV vaccination is important. Here, the authors demonstrate RSV neutralizing antibodies and RSV prefusion IgG binding antibodies as CoP for mRNA vaccination against RSV disease.

In a large prospective phase 4 trial, vaccination with CoronaVac, an inactivated SARS-CoV-2 vaccine, elicited significantly lower virus-specific IgG antibodies and neutralizing antibodies in patients with autoimmune rheumatic diseases than in age- and sex-matched healthy control trial participants.

TRPV4 dominant mutations cause neuropathy. Here, the authors show that TRPV4 binds and interacts with RhoA, modulating the actin cytoskeleton. Neuropathy-causing mutations of TRPV4 disrupt this complex, leading to RhoA activation and impairment of neurite extension in cultured cells and flies.

An integrated structural biology approach uncovers the structural complexity of the intrinsically disordered region (IDR) within the TRPV4 ion channel. Multiple stimulatory and inhibitory elements were identified within the IDR that modulate channel activity in a lipid-dependent manner.

Characterising the response to SARS-CoV-2 post vaccination is critical in the appraisement of the induced immune response, performance and protective potential. Here the authors present data from a phase 4 clinical trial in autoimmune rheumatic disease patients 6 months post second dose of Sinovac-CoronaVac inactivated vaccine that show a marked reduction in antibody particularly in males or those under treatment with immune targeting therapies but saw no rise in COVID-19 disease.

A tandem BRCT-domain-associated ubiquitin-dependent recruitment motif in BARD1 recruits BRCA1 to DNA double-strand breaks (DSBs) to promote homologous recombination and antagonize the 53BP1 DSB repair pathway that mediates non-homologous end joining.

Nakamura et al. show that DNA repair pathway choice and initiation of homologous recombination is guided by the recruitment of BRCA1 to post-replicative chromatin by BARD1 recognition of histone H4 tails unmethylated on lysine 20.

We have a limited understanding of how cells mark and identify newly replicated genomic loci that have a sister chromatid; here, unmethylated K20 in the tail of new histone H4 is shown to serve as a signature of post-replicative chromatin, which is specifically recognized by the homologous recombination complex TONSL–MMS22L.

Mitochondrial ribosomes (mitoribosomes) are characterized by a distinct architecture and thus biogenesis pathway. Here, cryo-EM structures of mitoribosome large subunit assembly intermediates elucidate final steps of 16 S rRNA folding, methylation and peptidyl transferase centre (PTC) completion, as well as functions of several mitoribosome assembly factors.

Development of a structure-based method to predict potential ARDs present in human metagenomes indicates that resistance genes are rarely transferred within the human gut, and that individuals can be clustered into resistotypes.

Changes in penguin populations on the Antarctic Peninsula in recent decades have been linked to environmental factors such as sea ice. Here, the authors show that penguin colony change on Ardley Island, NW Antarctic Peninsula during the last 8,500 years was primarily driven by volcanic activity.

Despite TRPV4’s medical importance, the mechanisms of ligand-mediated channel gating and its regulation by Rho GTPase are unclear. Here, the authors report the structures of TRPV4 in complex with RhoA and ligands, offering atomic-level insights into their functions.

β-Catenin can be oncogenic but finding inhibitors has been a challenge. Here, five compounds are identified, which attenuate transcriptional β-catenin outputs in colorectal cancer cells, and the response to one of them is shown to require an intrinsically labile α-helix next to the BCL9-binding site in β-catenin.

Multiple cryo-EM structures of rat TRPV1 at different temperatures illustrate steps in the heat-dependent gating of this important sensory receptor.

Human B cells can be edited to produce custom heavy-chain antibodies while allowing the cells to respond to immunization with a matched antigen.

Sequence-specific interactions between the Hepatitis B virus pre-genome and the core protein define the nucleocapsid assembly pathway and trigger virus-like particle formation. Cp-RNA contacts may regulate pre-genome organization, facilitating reverse transcription.

Development of multiple myeloma is preceded by precursor conditions. Here, the authors use single cell RNA-sequencing of plasma cells from patients across disease stages to identify genomic signatures present even at the earliest stages of disease.

We analyse a global dataset of genomic DNA sequences for Ophiuroidea to gain an understanding of phylogenetic divergence and biotic movement across oceans, finding phylogentically divergent faunas at shelf depths but greater connectivity of species at deep-sea depths.

In a large cohort of patients who underwent non-cardiac surgery, postoperative prescription of oral anticoagulation medication decreased the risk of stroke in patients with postoperative atrial fibrillation (POAF), especially for patients deemed to be at high risk for POAF based on a newly developed risk score.

Loss of PP2A activity is often associated with cancer but the underlying mechanism remains unclear. Here, the authors show that decreased methylation of PP2A catalytic C subunit caused by loss of LCMT-1 in prostate cancer abrogates the tumor suppressor activity of PP2A on AR/MED1-dependent gene expression, proposing decreased methyl-PP2A-C as a prognostic marker for prostate cancer progression.

The structure of the lithosphere and its impact on mantle flow significantly influence the impact of Earth’s interior dynamics on surface topography, suggest statistical analyses of Earth’s topography.

Acoustic communication is widespread, but not universal, across terrestrial vertebrates. Here, the authors show that acoustic communication evolved anciently, but independently, in most tetrapod groups and that these origins were associated with nocturnal activity.

The authors report an oviparous new specimen of the choristodere Ikechosaurus sp. from the Lower Cretaceous of China, confirming the basal archosauromorph affiliation of choristoderes. Phylogenetic analyses of this specimen along with other extinct and extant amniotes suggest that the ancestral amniote displayed extended embryo retention, including viviparity.

The inhibitor of kB kinase (IKK) is a central regulator of NF-kB signalling. Here the authors identify a motif conserved in substrates of canonical and alternative NF-kB pathways which mediates docking to catalytic IKK dimers: they show that phosphorylation of the conserved tyrosine suppresses the docking interaction.

A non-selective calcium channel transient receptor potential vanilloid 2 (TRPV2) is a potential drug target. Here, the authors employ cryo-electron microscopy, in silico docking, and electrophysiology to identify a binding site for an activator 2-aminoethoxydiphenyl borate (2-APB) in this channel.

Nuclear translocation of the p50/p65 heterodimer is essential for NF-κB signaling. Here, the authors identify a bipartite Nuclear Localization Signal in the NF-κB p50/p65 heterodimer that is recognized with high affinity by importin α3.

Charlotte Sumner and colleagues report that mutations in the ankyrin repeat region of TRPV4 cause Charcot-Marie-Tooth disease type 2C. Their functional studies indicate that the mutations result in increased channel activity.

Cryo-EM structures of TRPV3 in nanodiscs reveal lipids bound to the channel and unprecedented conformations of the selectivity filter and of the pore-lining helix S6, underscoring the importance of lipids for the channel structure.