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Adipose tissue (AT) inflammation is strongly associated with obesity and constitutes an obesogenic memory upon weight loss. Here, the authors show that intermittent fasting leads to an adipocyte p53-signaling dependent emergence of lipid-associated macrophages in visceral AT of obese mice which limits the systemic fasting response.

In hepatocellular carcinoma driven by non-alcoholic steatohepatitis, aberrant T cell activation and impaired immune surveillance seem to make hepatocellular carcinoma less responsive to anti-PD1 or anti-PDL1 immunotherapy.

One of the main shortcomings of cell therapy is the poor persistence and loss of functionality of donor cells after transfer. Using adjuvant drug–loaded nanoparticles conjugated directly to the surface of therapeutic donor cells, an approach designed to minimize the systemic side effects of adjuvant drugs, Matthias Stephan and his colleagues show enhanced functionality in a model of adoptive T cell therapy for cancer and of hematopoietic stem cell engraftment.

DNA-carrying nanoparticles can efficiently introduce leukaemia-targeting CAR genes into T cell nuclei, thereby inducing long-term disease remission.

Trans-ancestry meta-analysis of estimated glomerular filtration rate (eGFR) from 1,046,070 individuals identifies 264 associated loci, providing a resource of molecular targets for translational research of chronic kidney disease.

Sarcomas are morphologically heterogeneous tumours rendering their classification challenging. Here the authors developed a classifier using DNA methylation data from several soft tissue and bone sarcoma subtypes, which has the potential to improve classification for research and clinical purposes.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

A fundamental step in membrane protein biogenesis is their integration into the lipid bilayer with a defined orientation of each transmembrane segment. Here, the authors show that mutations in connexin 32 can cause failures in membrane integration which is detected by the ER chaperone machinery.

The poor correlation between brain Aβ deposition and clinical symptoms in Alzheimer´s disease remains puzzling. Here, the authors show a temporal dissociation of Aβ deposition and neurodegeneration.

Primary lymphomas of the central nervous system (PCNSL) are defined as diffuse large B-cell lymphomas (DLBCL) confined to the CNS. Here, the authors complete whole genome sequencing and RNA-seq to characterize 51 PCNSLs, and find common mutations in immune pathways and upregulated TERT expression and find distinct pathway differences between DLBCL and other primary CNS lymphomas.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

Periventricular heterotopia (PH) is associated with neurodevelopmental delay. Here authors report patient-derived organoids with FAT4 and DCHS1 mutations mimic PH features, showing hyperactivity, synaptic changes and cell morphological alterations.

There is currently no approved vaccine for Lassa fever virus (LASV). Here, Abreu-Mota et al. develop an inactivated, adjuvanted vaccine candidate expressing LASV glycoprotein (GPC) in a rabies virus vector, and show that non-neutralizing LASV GPC-specific antibodies are a major mechanism of protection.

A genome-wide association meta-analysis of individuals with clinically assessed or self-reported depression identifies 44 independent risk loci. Comparisons with other psychiatric disorders and candidate gene analyses provide new insights into major depressive disorder.

Burkitt lymphoma (BL) is the most common pediatric B-cell lymphoma. Here, within the International Cancer Genome Consortium, the authors performed whole genome and transcriptome sequencing of 39 sporadic BL, describing the landscape of mutations, structural variants, and mutational processes that underpin this disease how alterations on different cellular levels cooperate in deregulating key pathways and complexes.

In patients with Crohn’s disease, CD4⁺ T cells with cytotoxic T_H1 cell-like effector functions reactive against dietary and commensal yeasts are increased in blood and inflamed tissue compared with patients with ulcerative colitis and healthy controls.

A trans-ancestry genome-wide association study of serum urate levels identifies 183 loci influencing this trait. Enrichment analyses, fine-mapping and colocalization with gene expression in 47 tissues implicate the kidney and liver as key target organs and prioritize potential causal genes.

Analyses of genomes from 914 children, adolescents, and young adults provide a comprehensive resource of genomic alterations across a spectrum of common childhood cancers.

Keyl et al. present an explainable artificial intelligence model-based real-world data analysis from over 15,000 patients across 38 cancer types, identified key prognostic marker interactions, and confirmed these in an external lung cancer cohort.

PDEδ is a widely expressed factor that sustains the spatial organization and signalling of Ras family proteins. Here the authors describe the activity of Deltazinone 1, a new highly selective PDEδ inhibitor of KRAS-dependent cancer cell growth with low cytotoxic side effects.

Elucidating specific effects of protein kinase Akt isoforms remains challenging. Here, the authors establish an Akt isoform-dependent cellular model system and use it, together with X-ray crystallography and structure-based ligand design, to develop isoform-selective covalent-allosteric Akt inhibitors

Chordomas are rare bone tumors with limited therapeutic options. Here, the authors identify molecular alterations associated with defective homologous recombination DNA repair in advanced chordomas and report prolonged response in a patient treated with a PARP inhibitor, which later acquired resistance due to a newly gained PARP1 mutation.

Genome-wide association studies (GWAS) have become a key tool to discover genetic markers for complex traits; however, environmental factors that interact with genes are rarely considered. Here, the authors conduct a GWAS of obesity traits, and find that smoking may alter genetic susceptibilities.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

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.

Current SARS-CoV-2 diagnostic methods are sensitive yet poorly suited to testing whole communities on a regular basis. Here the authors present Cap-iLAMP that tests gargle lavage samples with an improved colorimetric RT-LAMP.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

An electrically pumped polariton laser is constructed using a quantum well microcavity, and its polaritonic nature is demonstrated unambiguously by using a magnetic field to probe the part-light, part-matter character of the system.

Swarm Learning is a decentralized machine learning approach that outperforms classifiers developed at individual sites for COVID-19 and other diseases while preserving confidentiality and privacy.

Proteomics can be used to refine cancer classification. Here, the authors characterise chronic lymphocytic leukaemia patients by proteogenomics, and identified a subtype of patients with poor prognosis associated with aberrant B cell receptor signalling.

While strain is known to affect cardiac electrophysiology, experimental systems to interrogate the effect of rapid strain cycles on cardiac tissue are lacking. Here the authors introduce a multielectrode array that can induce rapid dynamic strain cycles on cardiomyocyte strands and see effects of strain amplitude but not strain rate on impulse conduction.

This article considers the case of a 58-year-old man who presented with a 35-year history of Crohn's disease, pararectal fistulas and abscess formation. He had been taking azathioprine therapy for approximately 5.5 years. He was started on infliximab; however, his fistulas persisted and the abscess recurred. He was, therefore, switched to adalimumab. After development of pancytopenia, a bone marrow biopsy and a diagnostic splenectomy were performed, leading to a diagnosis of hepatosplenic T-cell lymphoma.

This article presents NAPstars, a family of genetically-encoded biosensors that enable real-time monitoring of NADP redox dynamics across species. The sensors reveal robust NADP redox regulation, cell-cycle-linked NADP oscillations, and glutathione as the major conduit for anti-oxidative electron flux.

Analysis of genotyping-by-sequencing data for more than 20,000 barley accessions from a German genebank provides a framework for genomics-assisted genebank management and analysis of large germplasm collections for important crops.

Non-alcoholic steatohepatitis (NASH) is characterized by lipid accumulation within hepatocytes and fibrosis. Seitz et al. show that the GTPase protein Rab24 is increased in the livers of people who are obese or have NASH.

Forced expression of C-X-C chemokine receptor type 6 in antigen-specific T cells enhanced the recognition and lysis of pancreatic cancer cells and the efficacy of adoptive cell therapy for pancreatic cancer.

Progressive respiratory failure is the primary cause of death in patients with COVID-19, but pathologies in other tissues may also occur. Here the authors report that adrenal tropism of SARS-CoV-2 is associated with adrenalitis, reduced adrenal cortisol levels and severe adrenal damage in a post-mortem case series of patients with severe fatal COVID-19.

Genome-wide association meta-analyses of waist-to-hip ratio adjusted for body mass index in more than 224,000 individuals identify 49 loci, 33 of which are new and many showing significant sexual dimorphism with a stronger effect in women; pathway analyses implicate adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution.

Genomic analysis of 491 medulloblastoma samples, including methylation profiling of 1,256 cases, effectively assigns candidate drivers to most tumours across all molecular subgroups.

Dörr, Lacy et al. evaluate the association between SARS-CoV-2 vaccination status and influenza-like illness and sick leave among 1745 Swiss healthcare workers. SARS CoV-2 vaccination is associated with increased illness symptoms and more days of sick leave, while influenza vaccination is associated with a decreased risk of both outcomes.

Point defects in solids have potential applications in quantum technologies, but the mechanisms underlying different defects’ performance are not fully established. Nagy et al. show how the wavefunction symmetry of silicon vacancies in SiC leads to promising optical and spin coherence properties.

Entanglement between photons and stationary quantum nodes is a fundamental resource for quantum communication, but typical transition wavelengths are far from the telecom band. Here, the authors deal with the problem using polarisation-independent, entanglement-preserving frequency conversion.