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At present, there are no countermeasures against the GI genogroup of noroviruses. The authors characterize a protective human antibody that broadly recognizes this genogroup.

Gorman et al. designed a Lassa virus prefusion-stabilized soluble glycoprotein complex trimer (GPC), with which they identified a Lassa virus-neutralizing nanobody that bound the GPC apex and elicited neutralizing antibody responses in guinea pigs.

Circulating tumour DNA profiling in early-stage non-small-cell lung cancer can be used to track single-nucleotide variants in plasma to predict lung cancer relapse and identify tumour subclones involved in the metastatic process.

A multi-ancestry genome-wide association meta-analysis of kidney cancer identifies 63 regions associated with disease susceptibility including one locus that was associated with increased risk in individuals with African ancestry.

A diverse collection of potent neutralizing antibodies against the SARS-CoV-2 spike protein have been isolated from five patients with severe COVID-19 and high serum neutralization titres.

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.

Homotrimeric DARPin molecules neutralize SARS-CoV-2 variants of concern by targeting a critical ACE2-binding interface.

Excessive activity of matrix metalloproteinases (MMPs) occurs in many diseases; however, the systemic administration of MMP inhibitors can cause undesirable, off-target effects and hence, clinical translation has been hampered. Now, injectable polysaccharide-based hydrogels are shown to enable the localized delivery of an inhibitor of MMP following the hydrogels’ degradation in response to MMP activity. This targeted approach shows efficacy in a myocardial infarction model in large animals.

Here, the authors analyse the distance between the body of an antibody and a protein antigen denoted as the Antibody-Framework-to-Antigen Distance (AFAD) for about 2000 non-redundant antibody-protein antigen complexes in the Protein Data Bank. They observe that antibodies with exceptionally long AFADs were all broad HIV-1-neutralizing antibodies that targeted densely glycosylated regions on the HIV-1-envelope trimer. The connection between long AFAD and dense glycan was further validated by the cryo-EM structure of antibody 2909 recognizing a glycan hole and by glycan shielding analyses based on molecular dynamics simulations.

A bulky residue in the stem ___domain of the influenza virus H2 hemagglutinin appears pivotal in eliciting broadly cross-reactive antibodies capable of recognizing diverse group 1 influenza subtypes and is informative for universal influenza vaccine development.

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.

Trials in rhesus macaques show that a subunit vaccine against SARS-CoV-2, comprising the spike protein receptor-binding ___domain displayed on a nanoparticle protein scaffold, produces a robust protective response against the virus.

The crystal structure of V1/V2, the only unresolved portion of the HIV-1 gp120 envelope glycoprotein, is reported in complex with human antibody PG9 and reveals a paradigm of antibody recognition with implications for vaccine development.

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.

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).

In order to get to their target sites, nearly all DNA binding proteins need to use some form of facilitated diffusion—for example, hopping, jumping, sliding and/or intersegmental transfer. Doing so can be made more difficult when nucleosomes are in their way. But is that really the case? Green and coworkers examine two different mismatch repair proteins using single-molecule microscopy and chromatin curtains and find that one can readily bypass the nucleosome by hopping over it while the other slides along until it is stopped in its tracks by the nucleosome. These types of studies can be used to distinguish between these different types of facilitated diffusion along chromatin.

In the TRACERx cohort of 171 patients with lung cancer, the ultrasensitive detection of ctDNA improves preoperative patient stratification, also in early-stage disease.

The third variable (V3) loop on the HIV-1 Env glycoprotein is required for viral entry. Here, the authors applied DARPin technology to produce broadly neutralizing inhibitors targeting a region of V3 that becomes accessible after binding to the CD4 receptor.

Plasmodium antigens called RIFINs bind to specific antibodies that incorporate the inhibitory receptor LILRB1 through its D3 ___domain, illustrating the principle of receptor-containing antibodies.

Methods for imaging vibrations in mechanical resonators have been limited to picometer amplitudes and frequencies above 2 GHz. Here, the authors use a stroboscopic optical sampling approach, with simultaneous high bandwidth and low noise-floor, and measure 70 fm displacements out to 12 GHz.

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 longitudinal study of an individual patient developing neutralizing antibodies against HIV-1 (targeting the V1V2 region of gp120) reveals how such neutralizing antibodies develop and evolve over time, providing important insights relevant to vaccine development.

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.

Endothelial cells from vascular-dependent central nervous system (CNS) diseases reveal reactivated fetal pathways, display common hallmarks of disease — including a partial loss of arteriovenous specification and CNS-specific properties as well as an upregulation of MHC class II receptors — and play a key role in the human brain neurovascular unit across development, adulthood and disease.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

Cryo-ET and subtomogram averaging analyses are used to determine structures of HIV-1 Env trimers on the surface of inactivated virions.

Cryo-EM structures of simian immunodeficiency virus (SIV) envelope trimers with neutralizing antibodies reveal mechanisms—conserved throughout SIV evolution—of immune evasion through extended variable loops and glycan shielding, involving both N- and O-linked glycans.

Crystal structures of HIV-1 Env V1V2 in complex with human broadly neutralizing antibodies and ontogeny analyses allow the engineering of Env trimers that are recognized by ancestor and intermediate antibody forms.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Multi-modal profiling reveals major alterations in colonic B cells in patients with ulcerative colitis, including reduced clonal diversity of plasma cells, and suggests that circulating gut-homing plasmablasts could serve as a biomarker for disease activity.

Acoustic waves can be used to manipulate particles and fluids in biomedical applications. The authors show that slip at the fluid-solid interface, characterized by a lower acoustic transmission into the fluid, is similar to Amontons-Coulomb friction, as found between solids. 

RIFINs are Plasmodium surface antigens that suppress the immune response by binding inhibitory receptors such as LAIR1. Here, Xu et al. characterize the interaction between RIFIN-variable 2 ___domain and a LAIR1 ___domain and identify LAIR1-binding RIFINs in several Plasmodium species.

An alternative HIV vaccine design facilitates generation of HIV-1-antibodies, with promising neutralization breadth in rodents and nonhuman primates.

Knowledge on how antibody responses have evolved is critical for the induction of protective immunity. Here the authors analyse, using high-throughput sequencing of both exon and intron regions, the mutation and lineage development of an HIV-neutralizing antibody to find an unexpected early emergence of broadly neutralizing species.

Patient-derived xenografts are important tools for cancer drug development. Here, the authors develop models from 22 non-small cell lung cancer patients. They show genomic differences between models created from different spatial regions of tumours and a bottleneck on model establishment.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

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.

Results of the TRACERx study shed new light into the association between body composition and body weight with survival in individuals with non-small cell lung cancer, and delineate potential biological processes and mediators contributing to the development of cancer-associated cachexia.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

The structure of the ligand-free HIV-1–Env trimer allows conformational fixation of Env and generation of an antigen that binds CD4 with high affinity and is recognized by broadly neutralizing antibodies but not poorly neutralizing ones.

The transcription machinery must locate specific promoter sequences among a vast excess of nonspecific DNA. Real-time single-molecule experiments with E. coli RNA polymerase, combined with theoretical calculations, suggest that facilitated diffusion does not contribute to promoter targeting at physiologically relevant protein concentrations but that instead the promoter search is dominated by three-dimensional diffusion.

A crystal structure of the human immunodeficiency virus Env trimer, used by the virus to infect cells, is determined here; the new structure, which shows the pre-fusion form of Env, increases our understanding of the fusion mechanism and of how the conformation of Env allows the virus to evade the immune response.

The heterodimeric cytokine IL-27 consists of the subunits p28 and EBI3. Hunter and colleagues demonstrate that p28 acting alone can inhibit the signaling of many cytokines by interfering with the common receptor gp130.

Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.

Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.