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Neural mechanisms mediating information flow and processing in dendrites are not fully understood. Here the authors developed techniques to map bioelectrical excitations in the dendrites of neurons in acute slices of mouse brain tissue. They developed a holistic picture of the roles of dendritic excitations in spike back-propagation.

Genome-wide CRISPRi screens for modulators of androgen receptor (AR) protein levels using live-cell quantitative endogenous AR fluorescence reporters identify PTGES3 as a new regulator of AR stability and function in prostate cancer.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Smells are detected in the nose by odorant molecules binding to a specific G protein-coupled receptor on the cell surface. Here, authors have determined the atomic structure of a receptor bound to an odorant molecule that showing how the odorant binds and activates the receptor.

Non-random chemical mixings that are intrinsic to medium- and high-entropy alloys are difficult to detect and quantify. Here the authors perform a diffraction data-mining analysis, revealing nanoclusters of short-range orders in a CrCoNi alloy, and their impacts on chemical homogeneity and dislocations slip.

Analysis of the longest-lived mammal, the bowhead whale, reveals an improved ability to repair DNA breaks, mediated by high levels of cold-inducible RNA-binding protein.   

Thermal barrier coatings increase the temperature at which jet engines can function, but are subjected to large mechanical forces during service. Here, the authors use synchrotron X-ray diffraction to quantify strain at different depths in a thermal barrier coating subjected to thermal gradients and mechanical load.

This study identifies TriDTCs as a family of terpene cyclases responsible for harzianol I and wickerol A biosynthesis in Trichoderma fungi and are found to regulate Trichoderma’s chlamydospore and Aspergillus oryzae’s sclerotia formation through producing harzianol I.

Designing full-color spherical artificial eyes remains a challenge. Here, Long et al. report a bionic eye where each pixel on the hemispherical retina can recognize different colors based on the unique bidirectional photo response; with optical adaptivity and neuromorphic preprocessing ability

Crystal structures of BAK core domain dimers suggest a mechanism by which lipids contribute to the oligomerization of BAK, which is essential for BAK-mediated permeabilization of the mitochondrial outer membrane.

Hydrogel materials have emerged as versatile platforms for biomedical applications. Here this group reports an mRNA lipid nanoparticle-incorporated microgel matrix for immune cell recruitment/antigen expression and presentation/cellular interaction thereby eliciting antitumor efficacy with a single dose.

Jing et al. show that COVID-19 infection causes white adipose tissue (AT) browning in mice and hamsters, which is mediated by VEGF action in the AT. VEGF blockade can ameliorate browning phenotype and COVID-19-induced weight loss, potentially providing a strategy to treat infection-induced AT atrophy.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Hepatitis C virus (HCV) gains entry into host cells via envelope glycoproteins E1 and E2. Here, El Omari et al.present the crystal structure of the N terminus of the E1 ectodomain of HCV and show that it adopts a different fold than predicted.

The bicyclo[1.1.1]pentane (BCP) motif has drawn increasing attention recently in drug discovery. Now, a programmable bis-functionalization strategy has been developed to modularly access bridge-substituted BCP scaffolds, based on the inherent chemoselectivity of BCP bis-boronates (3° > 2°). This strategy should enable further structure–activity relationship studies of BCP-containing drug candidates and open the door to unexplored chemical space.

The human lipopolysaccharide receptor caspase-4 captures its cytokine substrate pro-IL-18 via a mechanism that is distinct from known caspase–substrate interactions, leading to inflammasome-independent IL-18 release from macrophages.

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.

Adoptive cell therapies (ACT) hold promise for cancer immunotherapy, but optimization is still an ongoing process. Here the authors report CD4-targeted, nanoparticle-based artificial antigen-presenting cells that expand CD4⁺ T cells capable of lysing tumor cell lysis in vitro, and CD8⁺ T cells showing antitumor activity in a mouse melanoma model.

Over 90% of calcareous nannoplankton species disappeared during the Cretaceous–Palaeogene mass extinction, which occurred after an impact event. Palaeontological analyses show that the extinction was most pronounced in the Northern Hemisphere oceans, possibly as a result of an increased concentration of particulates created by the impact in the north.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Zeinert et al. provide cryo-EM structures of the E. coli Mg²⁺ importer MgtA: unexpectedly, this P-type ATPase is a dimer with an uncommon transmembrane ion-binding site and knotted N-terminus, which are functionally important features.

¹³⁴Ce and ¹³⁴La have great potential as companion diagnostic isotopes for radiotherapeutics labelled with α-emitting ²²⁵Ac and ²²⁷Th. Now, by controlling the Ce^III/Ce^IV redox couple, the large-scale production, purification and characterization of ¹³⁴Ce- and ¹³⁴La-based radiolabels has been achieved and their use for in vivo positron emission tomography is demonstrated.

Characterization of DCAF16-based BRD4 molecular glue degraders revealed a trans-labeling mechanism termed ‘template-assisted covalent modification’, which opens a new path for proximity-driven pharmacology.

RPA protects the integrity of single stranded DNA during DNA repair processes. Here the authors show how RPA actively participates in DNA transactions through its interactions with the endonuclease Dna2.

The authors demonstrate nano-engineered thin film thermoelectric materials are attractive for practical solid-state refrigeration with semiconductor manufacturing and ultra-low 0.003-cc materials usage.

A mass spectrometry-based approach globally identifies protein regulators of metabolism and reveals the role of LRRC58 in controlling cysteine catabolism.

The current model for B-family DNA polymerases in archaea is one of single-subunit enzymes in contrast to the multi-subunit complexes in eukaryotes. Here the authors show that PolB1 fromSulfolobus solfataricusexists as a heterotrimeric complex in cell extracts.

During mitosis, kinesin-5 motors are thought to crosslink microtubules in a muscle-like sliding filament mechanism. By combining electron microscopy with other structural tools, the authors reveal how four kinesin-5 polypeptides are organized into bipolar minifilaments.

By separating high- and low-temperature fabrication processes, cantilevers that incorporate sensing electronics between a soft polymer core and hard ceramic layers can be made, providing high force sensitivity and robustness to harsh environments.

The authors model the transient temperature response of micro-thermoelectric devices with AC current applied, which is locally integrated under a transient hot spot. They develop a strategy for actively canceling the transient temperature variations.

The kinesin-3 KIF1C transports dense core vesicles in neurons and delivers integrins to cell adhesions sites. Here the authors show that KIF1C's autoinhibitory interactions are released upon binding of protein tyrosine phosphatase PTPN21 or cargo adapter Hook3 resulting in cargo-activated transport.

Insoluble protein expression continues to be a bottleneck for biotechnology. Here, Chilkoti and colleagues report a method for generating and identifying hypersoluble intrinsically disordered protein fusion tags to improve soluble protein expression and rescue protein function.

Here, the enzymatic activity of APOBEC3G resulting in conversion of 2′-deoxy-zebularine into a hydration product allowed the authors to capture the transition state, which provides a blueprint for designing a new class of transition state-mimicking inhibitors for this class of enzyme.

Induced proximity by molecular glues is a strategy that leverages the recruitment of proteins to facilitate their modification or degradation. Here the authors present unbiased quantitative proteomic, biochemical and computational workflows that uncover hundreds of CRBN molecular glue targets using recombinant protein and cell lysate.

Inflammasome assembly promotes the cleavage and oligomerisation of gasdermin D (GSDMD) and subsequent pore formation. Here the authors raise nanobodies to human gasdermin and characterize the pore formation process mediated by GSDMD and how antagonistic nanobodies prevent pyroptosis.

The insertion of metal atoms and heteroaromatic units provides a way to tune the optical, electronic and magnetic properties of graphene nanoribbons. Now the synthesis of a porphyrin-fused graphene nanoribbon with a narrow bandgap and high charge mobility has been achieved, and this material used to fabricate field-effect and single-electron transistors.

Quantitative analysis of the extinction spectra of dispersions of 2D materials is complicated by light scattering. Here, the authors investigate non-resonant scattering in suspensions of wide-bandgap nanosheets, and develop a general model which allows the scattering spectra to be used as metrics for particle size in nanosheet dispersions.