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Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

Whether and how prefrontal astrocyte Ca²⁺ signaling modulates different neuronal populations in aiding or inhibiting anxiety-like behavior remains not fully understood. Here authors show that prefrontal astrocytes encode anxiogenic cues and modulate excitatory and inhibitory neurons differently. Silencing prefrontal astrocytes heightens anxiety-like behavior and induces proteomic changes in astrocytes and neurons.

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).

Xu, Meng, St-Germain et al. report that S1P in HDL induces a calcium signalling cascade involving E-Syt1 that ultimately promotes the formation of contact sites between the endoplasmic reticulum and the plasma membrane, as well as HDL-derived cholesterol transport.

The COVID-19 pandemic has raised concerns about increased neuropsychiatric conditions in children and youths, with potential links to SARS-CoV-2 infection. Here, the authors analyze EHR data from 25 institutions, showing that COVID-19 positive children and youths have a modestly increased risk of developing neuropsychiatric conditions, such as anxiety, depression, and ADHD, compared to those who tested negative.

Here the authors unveil the essential role of MCL-1 for adult hair follicle regeneration and inhibition of proliferation stress-induced apoptosis in mice. They also identify a P53/MCL-1/BAK axis balancing proliferation and death of activated hair follicle stem cells to ensure proper hair growth.

Complement proteome engagement is strongly linked to kidney outcomes in diabetes. This translational study leveraged five cohorts of over 4,500 person-years and high-throughput proteomics to enable potential biomarker-guided drug development.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

Here the authors define an inter-protomeric mechanism of deglycosylation of human IgG antibodies for corynebacterial IgG-specific ENGases and demonstrate that in vivo CU43 treatment preserve the neutralizing capacity of anti-influenza IgG antibodies.

The STARD-AI statement, which was developed through a multistage process involving over 240 international stakeholders, provides a minimum set of criteria that allows for comprehensive reporting of AI-centered diagnostic test accuracy studies.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

A single-cell multiomics analysis of over 200,000 cells of the primary motor cortex of human, macaque, marmoset and mouse shows that divergence of transcription factor expression corresponds to species-specific epigenome landscapes, and conserved and divergent gene regulatory features are reflected in the evolution of the three-dimensional genome.

Vinuesa et al. identify patients with systemic autoimmunity and a TNIP1 variant that result in dysregulated B cell function. Mice with the orthologous Tnip1 mutation develop spontaneous autoimmunity associated with impaired mitophagy and autophagic silencing of proteins downstream of Toll-like receptor 7 signaling.

A mixed-precision heterogeneous memristor combined with a compute-in-memory artificial intelligence (AI) processor allows optimization of the precision, energy efficiency, storage and wakeup-to-response time requirements of AI edge devices, which is demonstrated using existing models and datasets.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

Shi et al. report a sulfonation-dependent vulnerability of liver tumors expressing the sulfotransferase SULT1A1 by showing their sensitivity to the small molecule YC-1 and identifying structurally related compounds that can be modified by SULT1A1.

This study details a process of duplicated (homoeologous) chromosome ‘scrambling’ in newly formed rice polyploids, indicating the possibility of natural ‘allo-to-autopolyploid’ evolution, with implications for polyploid crop breeding.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Myddosomes, in which MyD88 forms barrel-like scaffold structures for effector protein recruitment and activation, contain proteins that act at all stages and regulate all effector responses of the TLR signalling pathways.

Precise profiling of dendritic RNA regulation reveals how neuronal depolarization leads to ribosome switching onto short upstream open reading frames and new coding sequences to acutely modulate local protein synthesis.

Folates are B vitamins that are known to be important for embryonic development and other important processes. Here, the authors show that a specific folate acts as a signal to activate serotonergic neurons to control behavior in C. elegans via a metabolism-independent pathway that requires the folate receptor and a calcium channel.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

A sequencing chemistry that separates nucleotide identification from nucleotide incorporation achieves high accuracy.

The authors demonstrate 3D chemical imaging of organic and inorganic materials near or below one-nanometer resolution using multi-modal electron tomography, by fusing elastic and inelastic scattering signals.

Remaining drug-tolerant persistent (DTP) cancer cells limit the efficacy of targeted therapy in EGFR, ALK and KRAS mutant non-small cell lung cancer (NSCLC). Here, the authors show that focal adhesion kinase (FAK)-YAP signalling supports DTP cells promoting residual disease and targeting this pathway improved tumour response in NSCLC preclinical models.

The affected cellular populations during Alzheimer’s disease progression remain understudied. Here the authors use a cohort of 84 donors, quantitative neuropathology and multimodal datasets from the BRAIN Initiative. Their pseudoprogression analysis revealed two disease phases.

The Somatic Mosaicism across Human Tissues Network aims to create a reference catalogue of somatic mosaicism across different tissues and cells within individuals.

Combined patch clamp recording, biocytin staining and single-cell RNA-sequencing of human neurocortical neurons shows an expansion of glutamatergic neuron types relative to mouse that characterizes the greater complexity of the human neocortex.

Swanton and colleagues present a clonal expression signature, ORACLE, which, in combination with clinicopathological and molecular risk factors, can predict survival of patients with lung adenocarcinoma, and they prospectively validate its prognostic value.

The acidophilic fungus Acrodontium crateriforme is present in traps of the carnivorous plant Drosera spatulata and promotes prey digestion.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

The POU2F3–OCA-T complex is the master regulator of tuft cell identity and a prominent molecular vulnerability of tuft-cell-like small-cell lung cancer.

Immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS) infers B cell and T cell fractions from whole-genome sequencing data. Applied to the 100,000 Genomes Project datasets, circulating T cell fraction provides sex-dependent and prognostic insights in patients.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

There is no universal model for large earthquake recurrence, and an ensemble forecasting approach is desirable when dealing with paleoseismic records with few data points and large measurement errors.

The complexity of the brain adds another level of difficulty to our understanding of how the brain develops, matures and functions. Both structural and molecular components define brain functional connectivity, and its alteration may result in developmental, behavioral and social deficits. Uncovering the roots and mechanisms behind neurodevelopmental disorders, such as fragile X syndrome or autism, is the goal of several lines of research. Despite the challenges associated with studying these diseases, new advances are linking pathological genetic changes with mechanisms in the brain. In Bench to Bedside, Guoping Feng and Jonathan Ting peruse a study that uncovers how fragile X syndrome–causing gene mutations unleash a translation break that finally leads to overexpression of synaptic proteins that alter the proper transmission of signals at the synapse. Furthermore, changes in the brain during the development of a person can also provide information about when and where the diseased brain loses functional connectivity. In Bedside to Bench, Jeffrey Neul proposes that studying the functional networks in people with autism and other neurodevelopmental disorders, and correlating changes with functional connectivity in animal models of these diseases, will uncover the mechanisms of normal and abnormal development and suggest possible treatment strategies.

A broadly neutralizing antibody (bnAb) response is required to combat SARS-CoV-2 variants of concern (VOCs). The authors isolated and characterized a large panel of sarbecovirus bnAbs from vaccinated individuals who had recovered from COVID-19, finding that many of these antibodies were able to neutralize all VOCs, including Omicron, and demonstrate prophylaxis in mice infected with diverse sarbecoviruses.

Which combination of current genome sequencing and assembly approaches results in high-quality, complete diploid genome assemblies is determined.

Understanding how SARS-CoV-2 gains initial entry into the human body is a key step towards the development of prophylaxes and therapeutics for COVID-19. Here, the authors show that ACE2, the receptor for SARS-CoV-2, is abundantly expressed in the motile cilia of the human nasal and respiratory tract and is not affected by the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.