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During chronic but not acute inflammation, chromatin remodelling is influenced by nuclear autophagy through WSTF interaction with ATG8 in the nucleus, leading to WSTF nuclear export and its subsequent degradation.

Instrumental to the migration of antigen-scavenging immune cells, the lymphatic vessel entry receptor LYVE-1 interacts with the hyaluronan glycocalyx, anchored by the leucocyte hyaluronan receptor CD44. Here, dynamic force spectroscopy, crystal structures and MD simulations provide mechanistic insights.

Uniform, hierarchical 2D nanostructures with controlled shapes can be prepared from homopolymers with charged end-groups using a crystallization-driven assembly process.

Rhine et al. find that neuronal aging leads to widespread dysregulation of RNA biology, including mislocalization of splicing proteins like TDP-43, chronic cellular stress and reduced resiliency.

Mendelian randomization (MR) identifies causal relationships from observational data but has increased error rates when the genetic variants used as instruments come from a single region, a typical scenario when assessing molecular traits like protein or metabolite levels as risk factors. Here the authors introduce a single-region pleiotropy-robust MR method, validating the method on three ground truth sources, showing its capability to identify disease-causing molecular traits.

In this study, the authors report the CoVerage tool (www.sarscoverage.org) for viral genomic surveillance and show that it predicted SARS-CoV-2 Variants of Concern, of Interest and under Monitoring together with their antigenic and evolutionary alterations almost three months prior to their WHO designation.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

Non-syndromic orofacial cleft is a relatively common congenital anomaly. Many non-coding genetic variants are associated with this disorder but only a subset is functional. Here the authors use reporter assays and stem cells to reveal members of this subset.

Disulfide-based dimerization of modified identical and heterologous nanobody scaffolds enables higher-order assembly for high-resolution cryo-electron microscopy structure determination that is widely applicable to small protein targets.

Authors show that Antarctic glaciers deliver high particle loads to the ocean, rich in iron that is potential food for marine algae. Microscopy techniques reveal this iron interacts with carbon. Ocean tracers show this glacial iron reaches far offshore.

RH5, which is part of the trimeric RCR-complex essential for invasion, is a vaccine candidate for malaria. Here, Williams et al. show that monoclonal antibodies targeting each of the three proteins in the RCR-complex can work together to more effectively block the invasion of red blood cells by Plasmodium falciparum and design a combination vaccine candidate.

Here the authors combine a deep generative model with structure-based drug design and prospectively validate functionally active, nanomolar, A_2A adenosine receptor ligands and solve their crystal structures to close the Artificial Intelligence Structure-Based Drug Design loop.

California lies in the transition zone where mid-latitude regions are expected to become wetter and subtropical regions drier, and precipitation projections for the region remain uncertain. Here the authors use a multitude of models to show consistent increases in California precipitation under a business-as-usual scenario.

The RNA methyltransferase activity of SPOUT1/CENP-32 is crucial for accurate mitotic spindle organization. Here, the authors describe a neurodevelopmental disorder caused by bi-allelic pathogenic SPOUT1 variants with reduced activity and compromised function in spindle organization.

Genome-wide analyses identify common variants associated with 11 distinct neuropathology endophenotypes, providing insights into the mechanisms underlying the genetic risk of Alzheimer’s disease and related dementias.

Diverse plant species synthesize salicylic acid from phenylalanine through a pathway that includes a conserved triple-enzyme module that converts benzoyl-CoA to salicylic acid.

The sensitivity of mesothelioma to the treatment of immune checkpoint blockade remains elusive. Here this group reports a double blind, placebo-controlled, randomized phase III trial of PD1 inhibitor (Nivolumab) on 332 patients with relapsed mesothelioma, and to uncover determinants of efficacy.

In a unique cohort of twins followed from birth to 8 years of age, shotgun sequencing of stool samples reveals that the transmission, persistence and evolutionary adaptation of bacterial strains are structured by early-life diet and weaning.

Understanding synapse loss in Alzheimer’s disease has been hampered by a lack of human model systems. Here, the authors show that manipulation of physiological or pathological Aβ has differing effects on synapses in live human brain slice cultures.

Venous tumour thrombus can occur within renal cell carcinoma, and can require complex additional surgery and treatment. Here, the authors analyse multiparametric data from patients treated with axitinib and develop a machine learning model to predict neoadjuvant treatment response.

Electron-spin resonance spectroscopy can detect radical species in live cells, but the method suffers from limitations of spin-label stability and selectivity. Here, flavoproteins are employed as genetically encoded spin probes to reveal structural features of bacterial chemotaxis proteins in cell.

This study describes structures of the transcription factor brachyury revealing the mechanism of DNA recognition. They identify fragments using X-ray fragment screening and optimize these into potent ligands with potential as cancer therapeutics.

The role of vascular plasticity in brain function remains poorly understood. Here, the authors demonstrate that a significant portion of blood vessels in the adult brain periodically occlude and regress, a process that is associated with a reduction in neuronal activity.

Oestrogen negative breast cancer is associated with a poor prognosis. In this study, the authors perform a meta-analysis of 11 breast cancer genome-wide association studies and identify four new loci associated with oestrogen negative breast cancer risk. These findings may aid in stratifying patients in the clinic.

Most metabolic studies using traditional procedures fail to reveal the spatial patterning associated with metabolic flux and cellular metabolism within tissue microenvironments. Here, the authors show the application of multi-scale microscopy, machine learning-based image segmentation and spatial analysis to map the fate of nutrient-derived ¹³C across spatiotemporal scales.

Acute febrile illness is common in sub-Saharan Africa and causative agents are often unknown. Here, the authors perform metagenomic sequencing on samples from patients with acute febrile illness in Uganda for which no diagnosis was available through routine diagnostic screening.

Predicting seizure onsets may allow for seizure prevention in patients. Here, authors show two distinct phases that always preceded temporal lobe seizures in mice, with activity confined within these two phases failing to progress into a seizure.

The protocol provides instructions for the use of FunFit, a software package to quantitatively map smooth topographic landscapes and improve the analysis, reproducibility and processing of thermal scanning-probe lithography data.

The post-spinel transition in mantle composition, which occurs at 660-km depth in Earth’s mantle, takes place over a pressure range equivalent to 250 m in depth, according to multi-anvil experiments for realistic mantle compositions and temperatures.

A pulse of ocean acidification is reconstructed from the boron isotope composition of fossilized oysters at the Triassic-Jurassic boundary, implicating ocean acidification from volcanic outgassing as a kill mechanism during the extinction event.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

Protein phosphatase 5 (PP5) is expressed in many cell types but its role in cardiomyocytes is unknown. Here the authors show that PP5 binds and dephosphorylates elastic titin in cardiac sarcomeres, and that PP5 is increased in heart failure, reducing cardiomyocyte compliance.

Cardiac repair usually requires highly invasive interventional procedures. Here, the authors develop an injectable shape-memory cardiac patch and demonstrated its applicability in a myocardial infarction model.

Surface characterization of soft materialsin situis challenging due to the importance of non-covalent interactions. Now, a new chemical imaging method is reported that generates images of surface interactions by combining many molecular probe trajectories.

How Meckel-Gruber syndrome protein TMEM67 functions in ciliogenesis and Wnt signaling simultaneously is unknown. Here the authors show that TMEM67 is proteolytically cleaved by the matrix metalloproteinase ADAMTS9 generating two functional isoforms.