Search

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

Untreated HIV infection results in CD4 depletion and progression towards immunosuppression, but the impact of successful antiretroviral treatment in HIV-positive people and the impact on vaccine responses is less well known. Here, the authors establish a link between low vaccine-induced T cell immunity and residual inflammation in human disease despite therapy.

Pneumococcal infection of the cerebrospinal fluid results in bacterial lysis, the release of toxic factors and induction of neuroinflammation. Here, the authors show that the virulence factor pneumolysin enhances the neuroinflammatory response to Streptococcus pneumoniae by the enhancement of endocytosis.

Here the authors find that erythroblasts of myelodysplastic syndromes with SF3B1 mutation leading to inefficient erythropoiesis show DNA replication stress with accelerated forks and reduced R-loops. Restoring R-loops by a histone deacetylase inhibitor rescues erythroid differentiation.

Gómez-Sánchez et al. show that generation of phagophore–endoplasmic reticulum exit sites (ERES) membrane contact sites, mediated by Atg2 and the TRAPPIII complex, triggers Ypt1 activation, which is a signal to initiate phagophore elongation.

Recent outbreaks of pertussis have highlighted the importance of surveillance of vaccine-preventable diseases. Here, the authors performed a cross-sectional seroprevalence study of pertussis, diphtheria, and tetanus in Europe and found evidence of circulation of pertussis in middle-aged adults.

The International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.

PACS1 syndrome is caused by an Arg203Trp mutation in PACS1. Here, the authors show that PACS1^R203Wdysregulates HDAC6 to disturb neuronal structure and function in a mouse model, and that silencing PACS1^R203W/HDAC6 reverses these deficits.

Nanobodies are normally made from immunized camelids, Ig transgenic mice or synthetic libraries. In this study, the authors introduce the llama Ig heavy chain locus into mice lacking this locus, thereby generating a line in which nanobodies can be made by direct immunization in the absence of an endogenous antibody repertoire.

Gao, Mathur, Tam and colleagues characterize transcriptomic and epigenomic alterations at the maternal–fetal interface in patients with COVID-19, thereby providing insights into aberrant pregnancy outcomes associated with SARS-COV-2 infection.

Here the authors show that a Gamma-based subunit vaccine induces broadly neutralizing antibodies against SARS-CoV-2 variants including Omicron, induces cellular immune responses, and protects mice from infection with Omicron BA.5 SARS-CoV-2.

A vaccine targeting stress proteins expressed by many cancers blocks a tumour escape mechanism, enabling protective immunity mediated by diverse T cell and NK cell populations.

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.

The Candida albicans toxin, candidalysin, is embedded in an unusual conserved precursor peptide sequence (Ece1). The precursor is not required to block premature pore-forming toxicity, but rather to prevent candidalysin auto-aggregation.

Although ageing is the most important risk factor for chronic ailments, effective interventions remain rare. Here, the authors identify the flavonoid 4,4’-dimethoxychalcone and demonstrate that it extends lifespan and promotes health in multiple organisms by inducing autophagy.

Analysis of the ability of Spike proteins from 26 human or animal coronaviruses (CoVs) to use ACE2 receptors across nine reservoir, potential intermediate, and human hosts reveals determinants of ACE2 receptor usage for diverse CoVs.

Spermidine, a naturally occurring polyamine, extends the lifespan of mice and is cardioprotective in both aged mice and hypertensive rats. In humans, high dietary spermidine intake is associated with reduced blood pressure and a lower incidence of cardiovascular disease.

Multiple variants of SARS-CoV-2 are inhibited by a trispecific DARPin.

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.

A study of SARS-CoV-2 variants examining their transmission, infectivity, and potential resistance to therapies provides insights into the biology of the Delta variant and its role in the global pandemic.

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.

Nebulized mRNA delivery has broad therapeutic potential but has proven challenging. Here, the authors report on a modified lipid nanoparticle with improved conditions to allow nebulization and demonstrate its application for delivering mRNA to the lungs.

The evolutionary origin of the human malaria parasite Plasmodium falciparum has been much debated. Genetic analysis of a large number of faecal samples from wild-living African apes now shows that Plasmodium parasites from Western gorillas are most closely related to the human parasite. The data suggest that human P. falciparum evolved from a gorilla parasite after a single host transfer event.

AQRNA-seq allows accurate quantification of small RNAs.

Sabrina Adam et al. use a deep enzymology method to study the effect of neighboring DNA sequence variation on the in vitro activity of Tet1 and Tet2. Their results suggest that flanking sequences could represent an important parameter that influences genomic DNA modification patterns.

Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

Adipose tissue expansion occurs via enlargement of adipocytes as well as the generation of new fat cells, the latter being associated with more favorable metabolic outcomes. Here, the authors show that activation of adipocyte Piezo1 results in release of FGF1 and stimulates the differentiation of adipocyte precursor cells.

AND-1, the vertebrate orthologue of Ctf4, is a critical player during DNA replication and for maintenance of genome integrity. Here the authors use a conditional AND-1 depletion system in avian DT40 cells to reveal the consequences of the lack of AND-1 on cell proliferation and DNA replication.

Infection of mice with Citrobacter rodentium is a common model of infection with attaching-and-effacing pathogens. Here, Connolly et al. analyse the transcriptome of C. rodentium during mouse infection, showing host-induced coordinated upregulation of virulence factors and 1,2-propanediol metabolism.

MicroRNAs have been best characterized for their functions in the cytoplasm; however, there is growing evidence of a nuclear localized role. Here, the authors identify Sfpq as an Ago2-interacting protein that modulates miRNA activity in both the nucleus and cytoplasm.

The GREGoR consortium provides foundational resources and substrates for the future of rare disease genomics.

While single atom catalysis combines heterogeneous materials with molecular understanding, the role of the single atoms remains vague. Here, authors examine single Ni on MoS₂ via in situ X-ray absorption spectroscopy to reveal the intermediate and catalytically active species.

While heterogeneous catalysts can act as tangible, efficient materials for energy conversion, understanding the active catalytic sites is challenging. Here, authors engineer specific catalytic sites into molybdenum sulfide to improve and elucidate hydrogen evolution electrocatalysis.

The spatial architecture of multiple myeloma remains to be explored. Here, the authors perform bulk and single cell sequencing for samples from newly diagnosed patients and reveal gene signatures associated with focal lesions and spatial heterogeneity in the tumour microenvironment.

The vast majority of BRCA1-driven breast cancers derive from luminal progenitor cells but the mechanisms of this lineage specificity are unclear. Here the authors show that dangerous accumulation of DNA-RNA hybrid structures due to RNA polymerase II pausing, occurs specifically in luminal epithelial cells.

Unbiased screening for insect gene function has been largely restricted to Drosophila. Here, Schmitt-Engel et al. perform an unbiased large-scale RNAi screen in the red flour beetle Tribolium castaneumto identify putative gene functions.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

RNA viromes from soil, sediment and animal faecal samples in China reveal the diversity and dynamics of the RNA virosphere.