Search

This study reports a motif of local field potentials that maps onto the anatomical layers of the cortex, is preserved across macaque cortical areas and across primates and may represent a ubiquitous layer-based and frequency-based cortical mechanism.

Glioblastoma is thought to arise from neural stem cells. Here, to investigate this, the authors use single-cell RNA-sequencing to compare glioblastoma to the fetal human brain, and find a similarity between glial progenitor cells and a subpopulation of glioblastoma cells.

Identifying functional domains and genetic regulatory mechanisms is essential for developing new therapies. Here the authors present sc-Tiling, single-cell high-density CRISPR tiling screening for functional domain characterization.

Structural classification of mutations in the epidermal growth factor receptor causing non-small cell lung cancer is a better predictor of patient outcomes following drug treatment than traditional exon-based classification.

The genetic basis of how cells replicate their DNA is not well understood. Here, the authors identify >1000 genetic elements that control human replication and reveal a complex epigenetic system that regulates replication origin activities.

GPR25 and its ligand define the core chemoaffinity axis GPR25–CXCL17 of the integrated extraintestinal mucosal immune system, regulating how immune responses disseminate to non-intestinal barrier tissues and with implications for understanding and manipulating immunity and inflammation.

Here, the authors demonstrate that BRCA1-associated protein 1 (Bap1) regulates osteoclast’s capacity to degrade bone. Reprogramming of epigenetic-metabolic axis upon Bap1 loss inhibits bone degradation, preserving bone mass, making it a potential therapeutic target for osteoporosis.

Drugs with partial activity at the serotonin 3 receptors (5-HT₃R) are suited to normalize serotonin response in treating irritable bowel syndrome. Felt et al. demonstrate the mechanism of partial agonism in 5-HT_3AR using cryo-EM.

Ligands capable of accelerating and inducing enantioselectivity in C–H activations with base metal catalysts have remained elusive. Here, the authors report a ligand-accelerated enantioselective C–H alknylation, using a chiral BINOL ligand with a copper catalyst.

PIP₂ binds via electrostatic interactions to the N terminus of the dopamine transporter (DAT) to modulate its function in dopamine efflux. This regulation is necessary for Drosophila locomotor activity induced by the DAT substrate amphetamine.

Speciation reversal is known mainly from recently diverged lineages that have come into secondary contact following anthropogenic disturbance. Here, Kearns et al. use genomic and phylogenomic analyses to show that the Common Raven (Corvus corax) was formed by the ancient fusion of two non-sister lineages of ravens.

Starvation triggers autophagy by inhibiting mTOR signalling. Here, Moreau et al.identify an alternative, transcriptional activation pathway: starvation-induced JNK signalling upregulates Annexin A2 transcription, which in turn enhances actin-dependent transport of Atg9 vesicles from endosomes to autophagosomes.

Defence against type six secretion system (T6SS) effectors is thought to be mostly mediated by dedicated immunity proteins that antagonize specific effector proteins. Here, two envelope stress-response pathways, Rcs and BaeSR, are shown to regulate protection against the T6SS effector TseH by modulating the integrity of the bacterial envelope in a manner independent of immunity proteins.

TATA-binding protein (TBP) and a transcription factor (TF) IIB-like factor are important constituents of all eukaryotic initiation complexes. Here, the authors use a DNA origami-based force clamp to investigate the assembly dynamics of human initiation complexes in the RNAP II and RNAP III systems at the single-molecule level under pico newton forces.

This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual.

Pooling participant-level genetic data into a single analysis can result in variance stratification, reducing statistical performance. Here, the authors develop variant-specific inflation factors to assess variance stratification and apply this to pooled individual-level data from whole genome sequencing.

Ocean currents play a crucial role in the distribution of marine coastal species. Here the nuclear and chloroplast genomes of this eelgrass (Zostera marina L.) is used to trace its colonization history from its origin in the Northwest Pacific.

The mechanical microenvironment influences stem cell pluripotency. Here, the authors culture stem cells in microgels with controlled volumetric confinement and identify Plakoglobin as a mechanoresponsive regulator of pluripotency in mouse and human.

Copy number variants (CNVs) account for a major proportion of human genetic diversity and may contribute to genetic susceptibility to disease. Here, a large, genome-wide study of association between common CNVs and eight common human diseases is presented. The study provides a wealth of technical insights that will inform future study design and analysis. The results also indicate that common CNVs that can be 'typed' on existing platforms are unlikely to contribute much to the genetic basis of common diseases.

The validation and analysis of X-ray crystallographic data is essential for reproducibility and the development of crystallographic methods. Here, the authors describe a repository for crystallographic datasets and demonstrate some of the ways it could serve the crystallographic community.

Organogenesis is orchestrated by biochemical and biophysical stimuli. Here, Ma et al. generate a micro-patterned surface that provides mechanical cues which, when combined with biochemical signals, drive human pluripotent stem cells’ differentiation into beating cardiac microchambers resembling primitive hearts.

Hydrogen peroxide attracts immune cells and induces wound inflammation. Evans et al. show that hydrogen peroxide also leads to the production of thymosin β4–sulfoxide in zebrafish wounds and in mouse hearts after myocardial infarction, where it acts as an anti-inflammatory factor that promotes wound healing.

Current genetic mouse models of lung cancer develop multifocal tumours in all lobes, which limits their applicability to model radiotherapy of human disease. Here Herter-Sprie et aldevelop a method to induce single lung tumours in these models, allowing precise evaluation of radiation regiment efficacy.

Despite their complexity, ecological networks appear robust to species loss. Here, Strona and Lafferty use artificial life simulations and real-world data to show that such robustness applies to stable conditions, but can collapse when the environment changes.

Molecules can self-assemble to form ordered phases with defined shape and periodicity, but there are a limited set of morphologies reported. Here, the authors have manipulated block copolymer thin films via an iterative assembly process to form a diverse library of morphologies.

The search for experimental evidence of Majorana modes is an area of intense research in condensed matter and quantum physics and uncovering clear evidence is complicated. The authors investigate the impact of Joule heating which can influence the analysis of experimental features related to Majorana bound states in topological Josephson junctions.

The mechanism by which KCNEβ subunits slow the kinetics of KCNQ1 channels is controversial. Here, Barro-Soria et al.show that mutually independent voltage sensor movements underlie the initial activation delay, and a subsequent slower conformational change opens the channel.

Automated pathotyping of synovial tissue in arthritis is a major unmet need. Here, the authors develop and demonstrate the efficacy of an automated tissue and cellular pathotyping tool for inflammatory arthritis.

Mechanisms that operate during embryonic development to restrict cell fate are currently under investigation. Here the authors characterise the role of SCL/TAL1 at the onset of blood specification in embryonic development using mouse EB differentiation culture as a model system.

Generative models for the novo molecular design attract enormous interest for exploring the chemical space. Here the authors investigate the application of chemical language models to challenging modeling tasks demonstrating their capability of learning complex molecular distributions.

Self-assembly of block-copolymers yields nanoscale structures in a facile way, but the diversity of structures is limited. Here, the authors demonstrate how block copolymer layering can be used to access new non-equilibrium morphologies.

Petrels are wide-ranging, highly threatened seabirds that often ingest plastic. This study used tracking data for 7,137 petrels of 77 species to map global exposure risk and compare regions, species, and populations. The results show higher exposure risk for threatened species and stress the need for international cooperation to tackle marine litter.

Scaling neural machine translation to 200 languages is achieved by No Language Left Behind, a single massively multilingual model that leverages transfer learning across languages.

Zhang et al. show that the poly(GA) proteins produced in patients with C9ORF72 repeat expansions cause neurodegeneration and behavioral abnormalities when expressed in mice. The emergence of these phenotypes requires poly(GA) aggregation, and poly(GA) inclusions sequester HR23 proteins involved in proteasomal degradation, as well as proteins involved in nucleocytoplasmic transport.

Experiments in mice identify the medial septum as an extrahippocampal input region that is critical for social memory formation, and show that modulation of the medial septum by serotonin regulates the stability of social memories.

Mutations in CNTNAP2 have been associated with a syndromic form of Autism Spectrum Disorder. Here the authors show that forebrain organoids generated from induced pluripotent stem cells of patients with a syndromic form of ASD with a homozygous truncating mutation in CNTNAP2 displayed an increase in volume and total cell number, which is driven by abnormal cellular proliferation and neurogenesis.

The BMP antagonist Gremlin1 balances BMP and SHH signalling, endowing limb bud development with robustness. Here, the authors identify enhancers controlling Grem1 levels in an additive, and spatial regulation in a synergistic manner, providing digit patterning with cis-regulatory robustness and evolutionary plasticity.

Human induced pluripotent stem cell (iPSC) cells have been used to model disease in specific cell types. Here, the authors develop an automated long-term culturing platform of human iPSC neurons, astrocytes, and microglia and use it to model some cellular aspects of Alzheimer’s disease.

Scalable trajectory inference for multi-omic single cell datasets is challenging in terms of capturing non-tree complex topologies. Here the authors present a method, VIA, that scales to millions of cells across multiple omic modalities using lazy-teleporting random walks.

During microbial infection, proteins are modified by the ubiquitin-like protein ISG15. Here, the authors uncover RNF213 as a sensor for ISGylated proteins on the surface of lipid droplets, showing that RNF213 has antiviral properties but also directly targets intracellular bacteria in infected cells.

Oxidation states help chemists to understand the bonding, properties and reactivity of compounds, but they can be difficult to determine for metal ions in extended crystalline materials. Now, oxidation states manually assigned to metal–organic frameworks have been harvested from the Cambridge Structural Database and used to build a machine-learning model that predicts oxidation states in metal–organic frameworks with good accuracy.

The pedestrian-induced oscillation of the London Millennium Bridge is considered as an example of emerging synchronisation. Belykh et al. provide an alternative mechanism for emergence of coherent oscillatory bridge dynamics where synchrony is a consequence, not the cause, of the instability.

Recent studies suggest spatial segregation of tumor initiation and manifestation in IDH-WT glioblastomas. Here, the authors use serial MRI/3D-reconstruction, whole-genome sequencing and spectral karyotyping-based single-cell phylogenetic tree building to establish this unique evolutionary mode in a murine model.

Interneuron subtypes have distinct properties and spatial distributions. Here, the authors show that the molecular-genetic basis of cortical resting-state brain function is shaped by distributions of interneuron-related transcripts and may capture individual differences in schizophrenia risk.

Some of Earth’s earliest continental crust has been previously inferred to have formed from partial melting of hydrated mafic crust at pressures above 1.5 GPa (more than 50 km deep), pressures typically not reached in post-Archean continental crust. Here, the authors show that such high pressure signatures can result from melting of mantle sources rather than melting of crust, and they suggest there is a lack of evidence that Earth’s earliest crust melted at depths significantly below 40 km.

To better understand the phenotypic relationships of complex traits it is also important to understand their genetic overlap. Here, Frei et al. develop MiXeR which uses GWAS summary statistics to evaluate the polygenic overlap between two traits irrespective of their genetic correlation.