Medical research

Combination therapy with the anti-HIV-1 monoclonal antibodies 3BNC117 and 10-1074 maintains long-term suppression in the absence of antiretroviral therapy in individuals with antibody-sensitive viral reservoirs.

The structure of a complex containing calcitonin gene-related peptide, the human calcitonin gene-related peptide receptor and the G_s heterotrimer, determined using Volta phase-plate cryo-electron microscopy, provides structural insight into the regulation of G-protein-coupled receptors by receptor activity modifying protein 1.

Longer human lives have led to a global burden of late-life disease, and so interventions, including changes to lifestyle and medical innovations, are needed to prevent disease and increase late-life health.

Therapeutic T cells bearing ligands engineered to optimize adhesion and transmigration through the blood–brain barrier can be targeted to brain tumours.

Age-dependent epithelial expression of the innate immune receptor TLR5 in the gut of newborn mice selects against the presence of flagellated bacteria and influences microbiota composition throughout life.

The microRNAs miR-221 and miR-222 regulate the reprogramming of macrophages during the development of lipopolysaccharide tolerance, and increased expression of these microRNAs is associated with immunosuppression and poor prognosis in patients with sepsis.

A PI3KCA inhibitor reverses symptoms in a mouse model of PROS/CLOVES syndrome, which results from gain-of-function mutations in PI3KCA, and produces improvements in patients with PROS/CLOVES syndrome.

ADNP interacts with the chromatin remodeller CHD4 and the heterochromatin protein HP1 to form a complex termed ChAHP that represses gene expression independently of the histone H3K9me3 modification.

Normothermic machine perfusion of the liver improved early graft function, demonstrated by reduced peak serum aspartate transaminase levels and early allograft dysfunction rates, and improved organ utilization and preservation times, although no differences were seen in graft or patient survival.

A tissue culture system that provides an increasing intensity of electromechanical stimulation over time enables an in vitro model of cardiac tissue derived from human induced pluripotent stem cells to develop many of the characteristics of adult cardiac tissue.

A new magnetoencephalography system allows high-spatiotemporal-resolution imaging of human brain function in moving subjects.

Meta-analysis—the quantitative, scientific synthesis of research results—has been both revolutionary and controversial, with rapid advances and broad implementation resulting in substantial scientific advances, but not without pitfalls.

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

Using optical mapping and 3D ultrasound, the dynamics and interactions between electrical and mechanical phase singularities were analysed by simultaneously measuring the membrane potential, intracellular calcium concentration and mechanical contractions of the heart during normal rhythm and fibrillation.

A combination of TGFβ inhibition and checkpoint-inhibition therapy provokes a potent cytotoxic response against metastatic tumours derived from colorectal cancers in mice.

In humans, TGFβ signalling is associated with lack of response to immunotherapy in immune-excluded tumours; in mouse models of this immune phenotype, robust tumour infiltration by T cells and tumour regression are observed only when checkpoint inhibition is combined with inhibition of TGFβ signalling.

In a basket trial design, the efficacy of the pan-HER kinase inhibitor neratinib is tested in patients with 21 different tumour types, and responses are determined by mutation and tissue type, and are restricted to HER2-mutant cancers.

In vivo deuterium labelling reveals a quiescent population of long-lived human virus-specific memory CD8 T cells that maintain the epigenetic landscape of effector cells, which facilitates rapid responses to pathogen re-exposure.

Disulfiram is metabolized into copper–diethyldithiocarbamate, which binds to NPL4 and induces its aggregation in cells, leading to blockade of the p97–NPL4–UFD1 pathway and induction of a complex cellular phenotype that results in cell death.

High salt intake changed the gut microbiome and increased T_H17 cell numbers in mice, and reduced intestinal survival of Lactobacillus species, increased the number of T_H17 cells and increased blood pressure in humans.

Autologous transgenic epidermal stem cell cultures are used to reconstitute almost the entire epidermis of a patient with severe junctional epidermolysis bullosa.

Quantitive microbiome profiling reveals that total microbial load is an important determinant of enterotypes and may be a key driver of microbiota alterations in patients with Crohn’s disease.

Multiple transcriptome approaches, including single-cell sequencing, demonstrate that escape from X chromosome inactivation is widespread and occasionally variable between cells, chromosomes, and tissues, resulting in sex-biased expression of at least 60 genes and potentially contributing to sex-specific differences in health and disease.

The Haplobank contains over 100,000 individually reversibly mutagenized, barcoded, mouse embryonic cell lines; proof-of-principle experiments were used to search for genes that are required for rhinovirus infection and angiogenesis using forward and reverse genetic screens, respectively.

A novel quantitative approach to identify intact glycopeptides from comparative proteomic data sets, allowing inference of complex glycan structures and direct mapping of them to sites within the associated proteins at the proteome scale.

A synbiotic preparation of Lactobacillus plantarum and fructooligosaccharide was found to significantly reduce sepsis and infections of the lower respiratory tract in a trial involving rural Indian newborns.

Mouse models of breast carcinoma and other solid tumours show that selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors not only induce tumour cell cycle arrest but also promote anti-tumour immunity.

CMTM6 maintains PD-L1 at the plasma membrane by inhibiting its lysosome-mediated degradation and promoting its recycling.

A report of high-depth, short-read sequencing and de novo assemblies for 150 individuals from 50 parent–offspring trios as part of establishing a population reference genome for the GenomeDenmark project.

A huge smartphone dataset of physical activity yields global insights, revealing that activity inequality predicts obesity better than does volume of activity and that much of the inequality is a result of reduced activity in females.

The authors report the first-in-human application of personalized neo-antigen RNA vaccines in patients with melanoma.

The authors reprogram in vitro endothelial cells from adult mice into engraftable haematopoietic stem cells that display single-cell and multilineage properties, are capable of long-term self-renewal and can reconstitute T cell adaptive immune function.

Frequent dispersal and short-lived local transmission clusters fuelled the 2013–2016 Ebola virus epidemic in Guinea, Liberia and Sierra Leone.

Antisense oligonucleotides against ATXN2 improved motor neuron function and restored firing frequency in cerebellar Purkinje cells in mouse models of spinocerebellar ataxia type 2.

Increasing expression of the autism-associated gene Ube3a, either alone or in combination with seizures, not only impairs sociability in mice but also reduces expression of the synaptic organizer Cbln1 in the ventral tegmental area, thus weakening glutamatergic transmission.

Introducing chimeric antigen receptors into the endogenous T-cell receptor locus reduces tonic signalling, averts accelerated T-cell differentiation and delays T-cell exhaustion, leading to enhanced function and anti-tumour efficacy compared to random integrations.

PI3Kδ controls the expression of the recombinogenic enzyme AID; excessive AID activity caused by PI3Kδ inhibition can induce genomic instability in leukaemia and lymphoma cells, as well as in patients with chronic lymphocytic leukaemia treated with PI3Kδ inhibitors.