Search

The organization and force-generating property of actomyosin dictate the plasticity and behaviour of cells but the spatio-temporal regulation of this network is unclear. Here, the authors show that coupling between EpCAM/RhoA co-trafficking and actomyosin rearrangement is pivotal during cell spreading and polarization.

Substrate-rigidity-dependent microtubule acetylation is now shown to be triggered by mechanosensing at focal adhesions, and in turn controls the mechanosensitivity of Yes-associated protein (YAP) translocation, focal adhesion distribution, actomyosin contractility and cell migration.

Neoplastic pancreatic cysts are associated with invasive pancreatic cancer, but their origins and evolutionary relationships are unclear. Here, the authors present the evolutionary analysis of neoplastic cysts and report them as precursors of invasive pancreatic cancer, and that SMAD4/TGFBR2 alterations are likely drivers of invasion in a subset of cases.

Aging is associated with immune attrition that may impact the effectiveness of the immune system to protect the host from pathogens. Here the authors show that immune aging is associated with alterations in the Wnt/β-catenin signaling and reduced stem cell memory T lymphocytes, hinting the Wnt/β-catenin pathway as a potential therapy target.

Decreased functionality and expression of trypanosome haptoglobin-hemoglobin receptor (HpHbR) is one of the evolutionary modifications that have allowed Trypanosoma brucei gambiense to infect humans. Here, Horakova et al. show that hemoglobin uptake in African trypanosomes is mediated almost exclusively by HpHbR and relevant for slender-to-stumpy differentiation. T. b. gambiense is poorly competent to differentiate into stumpy forms compared to T. b. brucei, due to reduced functionality of HpHbR.

Herpes simplex virus-1 encephalitis is linked to variants in a small nucleolar RNA, suggesting a new mechanism for antiviral immunity in cortical neurons.

WAPL creates a pool of free cohesin that binds to cell-type-specific sites. This cohesin turnover is important for maintaining promoter–enhancer loops.

mTORC1 is an important regulator of muscle mass. Here, the authors show that the PHD1 controls muscle mass in a hydroxylation-independent manner. PHD1 prevents the degradation of leucine sensor LRS during oxygen and amino acid depletion to ensure effective mTORC1 activation in response to leucine.

DNA replication stress drives genome instability and cancer. Here, Ölmezer and colleagues show that the helicase activity of multifunctional enzyme Dna2 suppresses dead-end replication structures that impair chromosome segregation if not removed by Holliday junction resolvase Yen1 in yeast.

Severe COVID-19 is characterized by hyperinflammation, and there is a need for accurate predictive biomarkers of progression. Lehuen et al. demonstrate that patients with severe COVID-19 show a dramatic loss of MAIT cells, and those that do remain are in a highly activated state.

Boretto et al. demonstrate that organoids derived from patients with various types of endometrial pathologies can model disease traits and diversity, and can be used as a drug-screening tool.

A small-molecule inhibitor of the type III phosphatidylinositol 3-kinase, Vps34, binds the ATP binding pocket and prevents vesicle trafficking and autophagy.

Quantum dots encapsulated inside DNA icosahedra that display a single endocytic ligand are used to track compartmental dynamics along endocytic pathways.

The vascular, cellular and molecular changes underlying sex differences in mood disorders are unclear. Here, the authors show that blood-brain barrier dysfunction modulates anxiety- and depressive-like behaviors in female mice and endothelium-specific changes associated with maladaptive responses compared to resilience to stress.

In order to be practical, schemes for characterizing quantum operations should require the simplest possible gate sequences and measurements. Here, the authors show how random gate sequences and native measurements (followed by classical post-processing) are sufficient for estimating several gate set properties.

β-cell dysfunction in type 2 diabetes is associated with pathological aggregates of IAPP that accumulate in pancreatic islets. Here, the authors describe a novel antibody cloned from healthy elderly donors that selectively targets IAPP oligomers and protects from IAPP toxicity.

Digitisation of vast archives of histology slides provides opportunities to use machine learning to identify specific tissue substructures associated with disease. Here the authors use self-supervised learning on 1.7 million histology images from 23 human tissues. The model segments tissues, detects pathologies and predicts RNA expression, linking morphology and gene expression.

A complete description of how the motor protein kinesin-1 walks along microtubules is missing because of the lack of a key structure. Here, Cao et al. solve the apo-kinesin:microtubule structure, completing the structure set and permitting the description of the structural changes that occur during the nucleotide cycle and their functional consequences.

A terawatt laser filament is shown to be able to guide lightning over a distance of 50 m in field trials on the Säntis mountain in the Swiss Alps.

Analysis of eight taxonomic groups across 186 islands and 423 mainland regions reveals that those with the greatest gross domestic product per capita, human population density and area have the highest established alien species richness, with the strongest effects on islands.

Environmental change and species diversity could jointly affect the stability of animal communities. Here the authors use citizen science data on bats, birds, and butterflies along urbanization and agricultural intensification gradients in France to show that both environmental change and diversity loss destabilise communities, but in different ways.

Several tuberculosis drugs are prodrugs that have to be enzymatically activated during metabolism. Ethionamide is such a drug and is activated by the monooxygenase EthA. EthA is itself regulated by the transcriptional repressor EthR. Here Alain Baulard and his colleagues have designed inhibitors of EthR that boost the antimycobacterial efficacy of ethionamide both in vitro and in vivo. Current therapy with ethionamide requires the use of high doses, often eliciting side effects. Its combination with the EthR repressor should allow lower doses to be used.

Rare-earth ion (REI)-doped systems are well suited for realising coherent light-spin interfaces, but demonstrations of spectral hole burning (SHB) in optical transitions of REI-based systems have been so far limited to REIs dispersed in matrices. Here, the authors report on transient SHB in a binuclear Eu(III) complex.

Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.

Traumatic brain injury is associated with changes to the metabolome. Here the authors show that acute traumatic brain injury has distinctive serum metabolic patterns which may suggest protective changes of systemic lipid metabolism aiming to maintain lipid homeostasis in the brain.

HIV remission has been seen in people living with HIV after the cessation of antiretroviral therapy and is termed post treatment control. Here Passaes and colleagues present an SIV model that shows early initiation of antiretroviral therapy after SIV infection is linked to improved post treatment control upon cessation of antiviral therapy and associates with the expansion of an enhanced memory pool of CD8 + T cells‘.

New antimalarials are urgently needed. Here, the authors identify Open Source Malaria compound, OSMS-106, as a reaction hijacking inhibitor of the malaria parasite protein synthesis machinery, with potential use for treatment and prophylaxis.

Since the discovery of proton radioactivity in ^53mCo, there has been no direct measurement of its branching ratio. Here the authors report the first measurement of the weak proton decay in ^53mCo by combining results from advanced detection systems.

The basic five-digit limb of tetrapods has been altered many times during evolution, usually by the progressive loss of digits — this study tracks the molecular underpinnings of this change, showing that in comparison to mouse, the polarized gene expression in the bovine limb bud is progressively lost due to evolutionary alteration of the cis-regulatory sequences that control Ptch1 expression in response to SHH signalling in the digit-forming handplate.

Statins are effectively used to prevent and manage cardiovascular disease, but patient response to these drugs is highly variable. Here, the authors identify two new genes associated with the response of LDL cholesterol to statins and advance our understanding of the genetic basis of drug response.

A discrete block of thick ancient crust revealed by a crustal reconstruction suggests a complex geologic history for the southern highlands of Mars.

Herold et al. present an integrated meta-omics framework to investigate how mixed microbial communities, such as oleaginous bacterial populations in biological wastewater treatment plants, respond with distinct adaptation strategies to disturbances. They show that community resistance and resilience are a function of phenotypic plasticity and niche complementarity.

Nano-Raman spectroscopy reveals localization of some vibrational modes in reconstructed twisted bilayer graphene and provides qualitative insights into how electron–phonon coupling affects the vibrational and electronic properties of the material.

Here β-catenin, which has been implicated in neurological and psychiatric diseases, including depression, is shown to mediate resilience to chronic stress in mice through induction of Dicer and microRNAs in nucleus accumbens, a key brain reward region.

Analysing a database of >200,000 feeding links between >5,000 species in terrestrial and aquatic food webs, the authors show that specific trait combinations can be used to predict which predator species are characterized by high body-mass ratio interactions with their prey.

Phytoplankton and plant plastids have distinct evolutionary origins and membrane organization. Here Floriet al. show that diatom photosynthetic complexes spatially segregate into interconnected subdomains within loose thylakoid stacks enabling fast diffusion of electron carriers and efficient photosynthesis

Compared to Tween 80, a pea protein–arabinoxylan mix achieved similar vitamin D₃ bioavailability, reduced LPS-specific IgG, and had no effect on gut-bacteria distance or microbiota in mice, making it a promising alternative for vitamin D₃ delivery.

Aquatic CO₂ emissions are expected to increase if warming reduces photosynthesis relative to respiration. An analysis of streams across a 41 °C temperature gradient reveals that the thermal responses of respiration and photosynthesis are similar.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Deep interactome profiling by mass spectrometry (DIP-MS) combines affinity purification with native BN-PAGE fractionation and mass spectrometry to resolve protein complexes sharing the same target protein. The paper also presents PPIprophet, a data-driven neural network-based protein complex deconvolution approach.

While small molecules that destabilize actin filaments are readily available, artificially stimulating actin polymerization in cells typically involves genetic manipulation. Here, the authors design cell-permeable branched polyamines that promote lamellipodium formation by stimulating actin polymerization.

Here, the authors characterize immunological and microbiome alterations in a cohort of obese asthmatics, finding that disease severity negatively correlates with fecal abundance of Akkermansia muciniphila, and show in a mouse model that administration of A. muciniphila reduces airway hyper-reactivity and airway inflammation.

The field of wavefunction engineering using intraband transition to design infrared devices has been limited to epitaxially grown semiconductors. Here the authors demonstrate that a device with similar energy landscape can be obtained from a mixture of colloidal quantum dots made of HgTe and HgSe.

Theulot et al. introduce NanoForkSpeed, a nanopore sequencing-based method to map individual replication fork velocities on entire genomes. NFS shows that fork speed is uniform across yeast chromosomes except for a marked slowdown at pausing sites.

Thanks to their versatile redox behaviors, octahedral molecular sieves show promise in a range of electrochemical applications. Here the authors report a hexagonal polymorph of tungsten trioxide, an octahedral molecular sieve that exhibits fast proton (de)insertion for electrochromic devices.

The retromer complex is a multi-protein component of the endosomal protein sorting machinery. Here, Sangaré et al. identify unique features in the retromer complex of the parasite Toxoplasma gondii, and show that it is crucial for the biogenesis of secretory organelles in this pathogen.

Hybrids are often considered evolutionary dead ends because they do not generate viable offspring. Here, the authors show that sterile yeast hybrids generate genetic diversity through meiotic-like recombination by aborting meiosis and return to asexual growth.