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It remains critical to understand the genomic events in response to treatment of oesophageal adenocarcinoma (OAC). Here, the authors perform a multi-omics analysis of OAC patients from the DOCTOR phase II clinical trial, finding genomic features and immune clusters associated with survival.

Due to the pulsed nature of X-ray free electron laser (XFEL) instruments the majority of protein crystals, which are injected using continuous jet injection techniques are wasted. Here, the authors present a microfluidic device to deliver aqueous protein crystal laden droplets segmented with an immiscible oil and demonstrate that with this device an approx. 60% reduction in sample waste was achieved for data collection of 3-deoxy-D-manno-octulosonate 8-phosphate synthase crystals at the EuXFEL.

The mechanisms underlying plant-microbe interactions in coastal ecosystems are little explored. Here, the authors use multi-omics and biogeochemical measurements to investigate the saltmarsh cordgrass root microbiome and its role in coupling nitrogen fixation and sulfur cycling.

Meteorology measurements from NASA’s Perseverance rover on Mars reveal a diversity of processes at work in the atmospheric boundary layer at Jezero crater over a range of temporal scales.

Acquired resistance to immunomodulatory drugs is common in multiple myeloma patients, but rarely attributed to genetic alterations. Here, proteomic, phosphoproteomic and RNA sequencing analysis in five paired pre-treatment and relapse samples reveals a CDK6-regulated protein resistance signature.

Exome sequencing and copy number analysis are used to define genomic aberrations in early sporadic pancreatic ductal adenocarcinoma; among the findings are mutations in genes involved in chromatin modification and DNA damage repair, and frequent and diverse somatic aberrations in genes known as embryonic regulators of axon guidance.

Lavas erupted above subduction zones commonly show evidence for recycling of subducted sediments. Geochemical analyses of sedimentary rocks that experienced subduction indicate that trace elements in the sediments can be efficiently recycled, because metamorphosed sediments rise buoyantly from the subducting plate and undergo partial melting at high temperatures in the overlying mantle wedge.

A study describes the experimental infection of cattle with a highly pathogenic avian influenza H5N1 clade 2.3.4.4b genotype B3.13 strain using an aerosol respiratory route for heifers and an intramammary route for lactating cows.

Poeck and colleagues identify a microbiome signature in patients receiving allogenic stem cell transplantation, which is associated with protective immune-modulatory metabolites, improved survival and less transplant-related mortality.

Single-cell sequencing reveals pre-activated immunity as important for milder COVID-19 symptoms in children.

Time-resolved serial femtosecond crystallography is used to reveal the structural changes that stabilize the charge-separation steps of electron-transfer reactions in the photosynthetic reaction centre of Blastochloris viridis on a timescale of picoseconds.

Much genetic variation among humans can be accounted for by structural DNA differences that are greater than 1 kilobase in size. Here, using tiling oligonucleotide arrays and HapMap samples, a map of 11,700 copy number variations (CNVs) bigger than 443 base pairs has been generated. About half of these CNVs were also genotyped in individuals of different ancestry. The results offer insight into the relative prevalence of mechanisms that generate CNVs, their evolution, and their contribution to complex genetic diseases.

The genome of the malaria parasite Plasmodium falciparum contains a record of past evolutionary forces. Here, using 2537 parasite sequences from the Democratic Republic of the Congo, the authors demonstrate how drug pressure and human movement have shaped the present-day parasite population.

Acral melanoma occurs on the soles of the feet, palms of the hands and in nail beds. Here, the authors reports the genomic landscape of 87 acral melanomas and find that some tumors harbor a UV signature and that the tumors are diverse at the levels of mutational signatures, structural aberrations and copy number signatures.

Using the GTEx data and others, a comprehensive analysis of adenosine-to-inosine RNA editing in mammals is presented; targets of the various ADAR enzymes are identified, as are several potential regulators of editing, such as AIMP2.

5.33 million years ago, in an event known as the Zanclean flood, Atlantic waters refilled a mostly desiccated Mediterranean Sea which had become disconnected from the world's oceans; however, the nature, abruptness and evolution of this flood remain poorly constrained. Using borehole and seismic data and a model study, it is now suggested that 90 per cent of the water was transferred in a short period of a few months to two years, with peak rates of sea level rise in the Mediterranean possibly reaching more than 10 metres per day.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

Expression of ADAM8, a metalloprotease disintegrin, correlates with worse prognosis in pancreatic adenocarcinoma (PDAC). Here Schlomann et al. show that ADAM8 promotes PDAC invasiveness, and develop a peptide inhibitor that blocks ADAM8 function and impedes PDAC progression in mouse models.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

What a microbial strain is and how many strains make up a natural bacterial population remain elusive concepts. Here, Viver et al. analyse Salinibacter ruber isolates and metagenomes from two solar salterns, revealing gaps within the species sequence space that they use to define and quantify sub-species categories, such as genomovars and strains, that co-exist in a saltern pond.

Harrington et al report their discovery of Nemacol, which is a small molecule inhibitor of the vesicular acetylcholine transporter (VAChT). VAChT loads synaptic vesicles with acetylcholine and is a key point of vulnerability in animals. Harrington et al show that Nemacol has nematode selectivity and potential utility against nematode parasites.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

The authors demonstrate the presence of SARS-CoV-2 in the nasopharynx and brain, suggesting that the virus is present in the CNS and may enter through the olfactory mucosa, exploiting the close vicinity of olfactory mucosal, endothelial and nervous tissue.

Identification of febrile children at risk of death in low-resource settings can improve survival, but tools for their prompt recognition are lacking. Here, the authors show that sTREM-1 measured at clinical presentation predicts in-hospital mortality in febrile children in Uganda.

Carbon isotopic analysis reveals global biogeographic traits in shark trophic interactions, and sheds light on the diverse foraging behaviour of sharks.

Sharma et al. identify an early metabolic checkpoint dependent upon lactate dehydrogenase for newly activated B cells to enter germinal centers.

Systematic characterization of longitudinal tau variability in human Alzheimer’s disease using an unbiased subtyping algorithm reveals four trajectories of tau deposition with distinct clinical features.

Emerging SARS-CoV-2 variants of concern were detected early and multiple cases of virus spread not captured by clinical genomic surveillance were identified using high-resolution wastewater and clinical sequencing.

Necroptosis, a form of cell death, occurs in acute renal injury. Here, the authors show that ferroptosis—a form of cell death dependent on iron - also occurs during acute kidney injury, and show that an inhibitor of ferroptosis can improve survival in a mouse model of acute kidney damage.

Phenotypic variation and diseases are influenced by factors such as genetic variants and gene expression. Here, Barbeira et al. develop S-PrediXcan to compute PrediXcan results using summary data, and investigate the effects of gene expression variation on human phenotypes in 44 GTEx tissues and >100 phenotypes.

Flexible magnetic sensors with high sensitivity have a wide variety of medical and industrial uses, however, making such sensors robust and flexible at the same time can be challenging. Here, the authors demonstrate a high sensitivity flexible magnetic sensor that exhibits self-healing under an applied alternative magnetic field, with complete performance recovery.

A large empirical assessment of sequence-resolved structural variants from 14,891 genomes across diverse global populations in the Genome Aggregation Database (gnomAD) provides a reference map for disease-association studies, population genetics, and diagnostic screening.

Just over 30 years after HIV/AIDS was first recognized, three accounts of its ravages intrigue Robin Weiss.

Biochemical and structural characterization of a homozygous point mutation in the GPX4 gene (R152H) reveals loss of enzymatic function and resistance to degradation. Therapeutic treatments such as selective antioxidants can overcome R152H defects.

Zhang et al. show that high-protein diets increase atherosclerosis risk through macrophage mTORC1 activation associated with suppressed clearance of damaged mitochondria and increased apoptosis.

Lysosomal integral membrane protein-2 (LIMP-2) is a glucocerebrosidase receptor, which is linked to kidney failure and other diseases. Here the authors show that LIMP-2 is also a phospholipid receptor and present the lipid-bound structure of the LIMP-2 luminal domain dimer and discuss its lipid trafficking mechanism.

Miscarriage affects around 15% of clinically confirmed pregnancies. Here the authors carry out a large genome-wide association study for sporadic and multiple consecutive miscarriage and suggest links with placental biology.

Oxidative stress can promote neurodegeneration. Akassoglou and colleagues describe Tox-seq, a functional single-cell RNA sequencing method to identify oxidative stress transcriptional signatures in CNS-resident cells. Tox-seq identified coagulation and glutathione-redox pathway genes that are coupled to oxidative stress and that could be targeted by the glutathione-regulating small molecule acivicin.

A violation of Lorentz symmetry would represent a fundamental departure from the physics of the standard model. Searching for anomalous neutrino oscillations, the IceCube collaboration reports no violation, and puts stringent bounds on its existence.

In this study the authors identify a possible link between the gene FAM222A and brain atrophy. The protein it encodes is found to accumulate in plaques seen in Alzheimer’s disease, and functional analysis suggests it interacts with amyloid-beta.