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Native state proteomics of PV interneurons revealed unique molecular features of high translational and metabolic activity, and enrichment of Alzheimer’s risk genes. Early amyloid pathology exerted unique effects on mitochondria, mTOR signaling and neurotransmission in PV neurons.

Development of myeloid leukaemia in children with Down syndrome is a stepwise process. Here, the authors employ scRNA sequencing and phylogenetic analysis on patient samples from various disease stages to define the cellular and molecular features of this stepwise leukaemia development.

The study used snMultiome-seq to map gene expression and chromatin accessibility in human central amygdala cells from people with and without AUD. Here, the authors show that inhibitory neurons are most affected, with KLF16-driven regulatory changes and AUD-risk variants disrupting gene activity.

Glioma tumours are known to be heterogenous in mutation and gene expression patterns, but sampling limitations can lead to inaccurate detection of evolutionary events. Here, the authors carry out multi-omics analysis of multi-regional biopsies from 68 patients and show differential mutations in non-enhancing regions.

The mechanisms of neurovascular adaptations underlying stress resilience remain unclear. Here the authors show that the astrocytic endocannabinoid system modulates the blood–brain barrier changes during stress in adult mice.

The use of single cell sequencing has enabled more detailed analysis of the immune response to infection. Here the authors characterise the immune response to malaria infection in an endemic region using single cell transcriptomics indicating regulatory signatures associated with infection.

Vascular smooth muscle cells undergo complex transitions to multiple disease-related phenotypes in coronary artery disease. Using vascular smooth muscle lineage-traced single-cell RNA and ATAC sequencing, the authors map molecular spatiotemporal patterns of murine atherosclerosis and discover molecular mechanisms of TCF21-mediated coronary artery disease risk.

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.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

Operating devices close to a phase transition can improve performance due to the singular behaviour at critical points. An enhancement in sensitivity has now been achieved using the bistable transition point in a hybrid quantum system.

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).

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.

Urine can be used to easily analyse the health of patients. Here, the authors identify proteins in urinary extracellular vesicles that distinguish prostate cancer from benign lesions.

Iacobucci et al. present the single-cell transcriptomic profile of patients with B cell acute lymphoblastic leukemia, report enriched multipotency and develop a multipotency score that is associated with worse survival in pediatric patients.

How age affect the immune response to malaria is not fully understood. Here, the authors characterise the transcriptome and serum inflammatory cytokines in children and adults in response to malaria, showing that there is an increase of inflammatory chemokine and cellular responses in adults compared to children.

Detailed insight into how the brain responds to Trypanosoma brucei infection is lacking. Here, single cell and spatial transcriptomics are integrated to characterise this response, identifying a unique crosstalk between microglia and plasma cells.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Results of an early-phase breast cancer prevention trial demonstrate the potential for breast cancer prevention in premenopausal women with anti-progestin therapy by inducing epithelial–stromal remodelling and suppression of luminal progenitors.

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.

A robust, cost-effective technique based on whole-exome sequencing data can be used to characterize immune infiltrates, relate the extent of these infiltrates to somatic changes in tumours, and enables prediction of tumour responses to immune checkpoint inhibition therapy.

Here, via applying metagenomics and metabolomics analyses, the authors show that fecal microbiota composition and microbiota-derived metabolites predict the trajectory of respiratory function and death in patients with severe SARS-Cov-2 infection, suggesting the gut-lung axis to play an important role in the recovery from COVID-19.

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.

RNA sequencing data and tumour pathology observations of non-small-cell lung cancers indicate that the immune cell microenvironment exerts strong evolutionary selection pressures that shape the immune-evasion capacity of tumours.

An examination of motor cortex in humans, marmosets and mice reveals a generally conserved cellular makeup that is likely to extend to many mammalian species, but also differences in gene expression, DNA methylation and chromatin state that lead to species-dependent specializations.

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

In pancreatic neuroendocrine tumors (PanNETs) ATRX, DAXX, and MEN1 are commonly mutated (A-D-M mutant PanNETs). Here, the authors find in a cohort of PanNETS 58% are A-D-M mutant PanNETs, with a worse clinical outcome and differences in gene expression and methylation compared to A-D-M wild type cases- these gene expression differences suggest that A-D-M mutant PanNETs potentially originate from a cell type similar to alpha cells.

A conserved feature of metazoan meiosis is that it occurs in a syncytium. Here, the authors show that intercellular bridges that connect germ cells in a syncytium are critical for ensuring proper meiotic progression and fertility in male mice.

A multi-omics approach reveals that bifidobacteria metabolize the prebiotic lactulose to produce acetate and deconjugate bile acids, which is associated with reduced densities of drug-resistant pathogens and decreased incidences of infection in patients with liver disease.

Duplaquet, Li et al. identify and characterize KDM6A as an epigenetic regulator that impacts chromatin accessibility to modulate ASCL1-to-NEUROD1 subtype switching in small cell lung cancer.

Power et al. catalogue the microbial biodiversity and physicochemistry of around 1000 hotsprings across New Zealand, providing insights into the ecological conditions that drive community assembly in these ecosystems.

Preservation of oral microbiome ancient DNA from Oceania is much better than human ancient DNA. The authors leverage this to demonstrate that oral microbial community composition in Oceania is not only distinct from the rest of the world, but it may also be associated with patterns of ancient human migration in the region.

Wilcox et al. (2022) show that NMDA receptor channel blockers, some of which are clinically important drugs, can access their binding site via 2 routes: a well-known path from the extracellular solution, and another path through the plasma membrane.

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.

Here the authors show that persistent antigen stimulation drives the generation of CD8⁺ tissue-resident exhausted T cells with distinct developmental origins, function and therapeutic responsiveness when compared to CD8⁺ tissue-resident memory T cells.

Preclinical studies indicate that simultaneous HER2 and VEGF blockade may be beneficial in gastroesophageal adenocarcinoma (GEA). Here, the authors report the efficacy and biomarker analysis of a phase II clinical trial investigating the combination of bevacizumab (anti-VEGF) and standard-of-care CAPOX (capecitabine, oxaliplatin) and trastuzumab in previously untreated advanced HER2 + GEA.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

Current single cell protein expression profiling approaches come with substantial measurement noise. Here the authors discover the sources of this noise and develop a denoising algorithm that improves data quality and downstream applications.

The gbu gene cluster, present in the human gut microbiota member Emergencia timonensis, converts γ-butyrobetaine (γBB) to trimethylamine in the conversion of dietary l-carnitine, which is found in red meat, to the proatherosclerotic metabolite trimethylamine-N-oxide. Individuals with high plasma γBB levels had increased risk of cardiovascular events.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

T cell responses can be generated to either pathogen infection or from priming with a vaccine. Here the authors compare T cell generation, phenotype and single cell transcriptome of participants vaccinated with a mpox vaccine or infected with the virus showing that the virus induced T cells showed more effective function and phenotype.

Brucella melitensis is a zoonotic bacterial pathogen of livestock that can infect humans and causes brucellosis. Here, the authors sequence an ancient specimen of B. melitensis and show that the species emerged in the Neolithic period, around the time of development of animal management practices.

A hybrid AAV–transposon CRISPR approach enables large-scale in vivo screens in T cells and identifies potential targets for immunotherapy.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Trypanosome brucei is known to colonise the subcutaneous white adipose tissue and the interaction with the cellular locale could play key roles in pathogenesis and host response. Here the author’s use single cell approaches and in vivo animal models, and show a role for IL-17 in the adipose tissue response and parasite burden in a chronic murine model of infection.

Trypansome brucei infection can result in colonisation of the skin but how this impacts the skin architecture and immune response has not been fully resolved. Here the authors apply a spatially resolved single cell transcriptomics approach in a murine model of infection, and suggest a role for IL-17- producing γδ T cells in the immune response to T. brucei skin infection.