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This paper reports integrative molecular analyses of urothelial bladder carcinoma at the DNA, RNA, and protein levels performed as part of The Cancer Genome Atlas project; recurrent mutations were found in 32 genes, including those involved in cell-cycle regulation, chromatin regulation and kinase signalling pathways; chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far.

Henipaviruses (HNVs) infect bats in Asia and Africa, but transmission to humans (often with lethal consequences) is known only in Asia. Here the authors show that 3% of human serum samples from certain areas in Cameroon contain antibodies against HNV, indicating spillover into the human population.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Empirically based models of disease progression in familial frontotemporal dementia reveal the relative ordering of clinical, neuroimaging, and fluid biomarker changes and facilitate novel clinical trial designs

Post-traumatic stress disorder (PTSD) is a common mental health problem. Here, the authors report a GWAS from the Psychiatric Genomics Consortium in which they identify two risk loci in European ancestry and one locus in African ancestry individuals and find that PTSD is genetically correlated with several other psychiatric traits.

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology.

The degree to which human societies have responded to past climatic changes remains unclear. Here, using a novel combination of approaches, the authors show how volcanically-induced suppression of Nile summer flooding led to societal unrest in Ptolemaic Egypt (305–30 BCE).

Identification of cancer genes altered by non-genetic mechanisms in B-cell lymphoma is challenging. Here, the authors report the development of transposon tools to perform genome-wide recessive screens in vivo and validate identified putative tumor suppressor genes using a CRISPR/Cas9 validation platform.

AlphaFold 3 has a substantially updated architecture that is capable of predicting the joint structure of complexes including proteins, nucleic acids, small molecules, ions and modified residues with greatly improved accuracy over many previous specialized tools.

Plasmodium vivax, the leading cause of human malaria in Asia and Latin America, is thought to have an Asian origin. Here, the authors show that wild chimpanzees and gorillas in Africa are infected with parasites that are closely related to P. vivax, indicating an African origin for this species.

Here, the authors show structural, biochemical, and functional insights into the discovery of epichaperome‐ directed chemical probes for use in central nervous system diseases. Probes emerging from this work have translated to human clinical studies in Alzheimer’s disease and cancer.

The existence and properties of tetraquark states with two heavy quarks and two light antiquarks have been widely debated. Here, the authors use a unitarized model to study the properties of an exotic narrow state compatible with a doubly charmed tetraquark.

The development of single-molecule electronics calls for precise tuning of the electronic properties of individual molecules that go beyond two-terminal control. Here, Wickenburg et al. show gate-tunable switch of charge states of an isolated molecule using a graphene-based field-effect transistor.

A meta-analysis of genome-wide association studies in more than 66,000 individuals identifies 68 new genomic loci that reliably associate with platelet count and volume, and reveals new gene functions.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

High data volumes from multidimensional imaging techniques can lead to slow collection and processing times. Here, the authors implement multispectral fluorescence lifetime imaging microscopy (FLIM) that uses time-correlated photon counting technology to reach simultaneously high imaging rates combined with high spectral and temporal resolution.

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

Netrin-1, via precise Neo1/Unc5B stoichiometry, promotes naive pluripotency, embryonic stem cell self-renewal in combination with leukaemia inhibitory factor, and the formation of the mouse epiblast in vivo.

It is unclear whether stream detritivore diversity enhances decomposition across climates. Here the authors manipulate litter diversity and examine detritivore assemblages in a globally distributed stream litterbag experiment, finding a positive diversity-decomposition relationship stronger in tropical streams, where detritivore diversity is lower.

Glacial melt can modify heat transport, and therefore ocean processes, associated with ice front retreat, as revealed by direct observations from the Pine Island Bay region of Antarctica.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

Zhang and colleagues report that multicellular clusters of circulating tumor cells are more resistant to killing by natural killer (NK) cells through altered NK ligand expression, resulting in polyclonal metastases.

The authors show that norepinephrine signaling to astrocytes in the mouse visual cortex acts as a separate neuromodulatory pathway that regulates the effects of arousal on neuronal activity and cortical state.

Tau but not amyloid-beta pathology is associated with widespread alterations of histone 3 lysine 9 acetylation in the aged human cortex. Similar alterations of chromatin organization occur in iPSC-derived neurons after overexpression of tau.

An improved, fully re-annotated Aedes aegypti genome assembly (AaegL5) provides insights into the sex-determining M locus, chemosensory systems that help mosquitoes to hunt humans and loci involved in insecticide resistance and will help to generate intervention strategies to fight this deadly disease vector.

PMOs (phosphorodiamidate morpholino oligomers) have huge potential for antisense therapy but complex and slow synthesis limits application. Here, the authors report the development of automated flow synthesis methods which reduce nucleobase coupling times from hours to minutes removing human errors and allow for high-throughput production.

Which contralesional circuits adapt after traumatic brain injury (TBI) is unclear. Here the authors used in vivo imaging, retrograde labeling, rabies tracing, clearing and functional imaging to demonstrate that callosal neurons selectively adapt after TBI in mice.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

Dry-season climate variability is a primary driver of tropical tree growth, according to observations from a pantropical tree-ring network.

Neuronal patterns during working memory show low-frequency oscillatory activity. Here, the authors demonstrate a rhythmic retention of working memory information in theta and alpha frequency ranges. Moreover, phase-locked amplification of the retained information improves working memory performance.

This study uses gene expression predictors for the dorsolateral prefrontal cortex and other brain regions to perform a transcriptomic imputation analysis of schizophrenia, identifying 413 genic associations across 13 brain regions and 36 significantly enriched pathways.

The single-bond-resolved chemical structures of transient intermediates in a complex bimolecular reaction cascade were imaged by noncontact atomic force microscopy. Theoretical simulations reveal that the kinetic stabilization of experimentally observable intermediates is governed by selective energy dissipation to the substrate and entropic changes along the reaction pathway.

The competitive dynamics of mitochondrial haplotypes juxtaposed within the same cell are poorly studied. Here the authors show, in the context of a transmissible cancer, that one haplotype has recurrently entered cancer cells by horizontal transfer and appears to have a ‘selfish’ selective advantage.

The LHCb collaboration reports an improved measurement of the oscillation frequency of mesons consisting of a bottom quark and strange quark, which is then combined with previous results.

Single-molecule-based sequencing technology is applied to generate genome-wide maps of chromatin modifications in mammalian cells. Histone marks can discriminate genes that are active, poised for activation, or stably repressed and therefore reflect cell state and developmental potential.

Juan Cadiñanos and colleagues perform an insertional mutagenesis screen with a single-copy inactivating Sleeping Beauty transposon to look for Pten-cooperating tumor suppressor genes in mice. They find novel candidate cancer genes, verify their clinical relevance in patient cohorts and functionally demonstrate their synergistic relationship to Pten in tumor suppression.

V-domain immunoglobulin suppressor of T cell activation (VISTA) selectively engages P-selectin glycoprotein ligand-1 (PSGL-1) and suppresses T cells at acidic pH similar to those in tumour microenvironments, thereby mediating resistance to anti-tumour immune responses.

In chronic lymphocytic leukemia (CLL), evolution is driven by transcriptional and epigenetic heterogeneity. Here, the authors integrate epigenomic analyses to show how intra-tumoral epigenetic diversity results in divergent chromatin states in CLL cells, increasing cell-to-cell transcriptional heterogeneity.

Femtosecond laser pulses were used to heat dense matter, converting it into an extremely hot plasma. 52-times ionized gold was achieved as well as gigabar pressures, which can be exceeded only in the central hot spots of thermonuclear fusion plasmas.

CRISPR/Cas9 technology has been used for genome engineering in vivo. Here, the authors use a transfection technique to deliver multiple guide RNAs to the pancreas of adult mice, allowing genetic screening and chromosome engineering in pancreatic cancer.

Environmental influences during prenatal development may have implications for health and disease later in life. Here, Czamara et al. assess DNA methylation in cord blood from new-born under various models including environmental and genetic effects individually and their additive or interaction effects.

Four transcription factors Oct4, Sox2, c-Myc and Klf4 are known to convert fibroblasts to pluripotent stem cells, if Fbx15 expression is also selected. But the induced stem cells were shown to be distinct from normal embryonic stem cells. However, if cells expressing Nanog and Oct4 are selected, then the reprogrammed fibroblasts are similar to embryonic stem cells in both biological potency and epigenetic state.

Chromodomain Helicase DNA-binding (CHD) proteins have been implicated in neurodevelopmental processes. Here, the authors identify missense variants in CHD3 that disturb its chromatin remodeling activities and cause a neurodevelopmental disorder with macrocephaly and speech and language impairment.

Whole-genome bisulphite sequencing data from diverse human cell and tissue types shows that only about 22% of CpGs change their methylation state across these cell types; most of these CpGs are located at gene regulatory elements, particularly enhancers and transcription-factor-binding sites, and these selected regions with dynamic DNA methylation patterns could help to define putative regulatory elements further.

Neoadjuvant PD-1 blockade in patients with resectable melanoma followed by adjuvant maintenance results in early immunological effects driving clinical benefit and reveals transcriptional and genomic mechanisms of response.