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Clinical proteomics critically depends on the ability to acquire highly reproducible data over an extended period of time. Here, the authors assess reproducibility over four months across different mass spectrometers and develop a computational approach to mitigate variation among instruments over time.

The success of hematopoietic cell transplants is predicted by profiling minor histocompatibility antigens.

Reference assemblies of great ape sex chromosomes show that Y chromosomes are more variable in size and sequence than X chromosomes and provide a resource for studies on human evolution and conservation genetics of non-human apes.

The layout of cortical systems varies across people, which is assumed to be largely due to border shifts between nearby systems. Dworetsky et al. reveal a qualitatively different variation in systems that occurs at a distance from expected locations.

Targeted protein degradation uses small molecules to recruit proteins to E3 ligases to induce their ubiquitylation and degradation, but only a few human E3 ligases are amenable to this strategy. Here, the authors identify and characterize SP3N, a specific degrader of the prolyl isomerase FKBP12, containing an FKBP12 ligand appended with a flexible alkylamine tail that is metabolized to an active aldehyde species which recruits the SCF^FBXO22 ligase for FKBP12 degradation.

Heme is an abundant cofactor required by nearly all known organisms. Here, authors discover a cyanobacterial protein with a distinct Zn-mirror heme site, which may function to sense heme and regulate energy metabolism.

A metabolite screen of pancreatic cells shows that pancreatic cancer cells metabolize uridine-derived ribose via UPP1, supporting redox balance, survival and proliferation.

PolyFun is a computationally scalable framework for functionally informed fine-mapping that makes full use of genome-wide data. It prioritizes more variants than previous methods when applied to 49 complex traits from UK Biobank.

Pump–probe measurements conventionally achieve femtosecond time resolution for X-ray crystallography of reactive processes, but the measured structural dynamics are complex. Using coherent control techniques, we show that the ultrafast crystallographic differences of a fluorescent protein are dominated by ground-state vibrational processes that are unconnected to the photoisomerization reaction of the chromophore.

Squamous cell lung cancer has dismal prognosis due to the dearth of effective treatments. Here, the authors perform an integrated proteogenomic analysis of the disease, revealing three proteomics-based subtypes and suggesting potential therapeutic opportunities.

Post injury cytoskeletal modifications in neurons are not fully understood. Here the authors describe a pro-survival actin cytoskeletal reorganization in neurons triggered during a model of ischemic stroke.

Aedes aegypti can act as a vector for viral pathogens but the mechanism of viral resistance and evolving host-pathogen tolerance are poorly understood. Here the authors structurally characterise a duplicated pair of interacting Toll immunoreceptors and the cytokine ligand Spaetzle1C and show their dose-dependent function and mechanism of activation.

Based on coupled climate model simulations the authors show that changes to the Earth’s surface energy balance following global-scale forestation and deforestation may change the strength of the jet stream, the Hadley cell, and the ocean circulation, which alters remote climate patterns across the globe

Structural and physiological studies show that the inner membrane protein PbgA is a crucial sensor of lipopolysaccharide (LPS) and regulates the activity of the LPS biosynthesis enzyme LpxC.

Overexpression of complement C4A is associated with schizophrenia risk. Using a novel mouse model, Yilmaz et al. find that increased expression of C4A leads to abnormal synaptic pruning and behavior, suggesting its importance as a therapeutic target.

The tau protein is theorized to spread transneuronally in Alzheimers disease, though this theory remains unproven in humans. Our simulations of epidemic-like protein spreading across human brain networks support this theory, and suggest the spreading dynamics are modified by β-amyloid

T cell activation is a process that requires extra nutrients, which could be difficult to source from the tumor microenvironment in competition with tumor cells. Here authors increase the metabolic fitness of CAR-T cells by stable overexpression of the glucose transporter GLUT1, which allows them to increase their glucose intake and enhances their antitumour function.

Brain–machine interfaces typically decode arm velocity from motor cortical neurons to move neuroprostheses, but performance of these devices is degraded by erroneous extraction of speed from the neuronal firing patterns. Here, the authors show that this error can be corrected by using a hybrid artificial neural network approach.

Directed evolution of opsins via robotic high-content screening finds a fluorescent reporter of voltage that is simultaneously optimized for brightness, localization and voltage sensitivity and is applicable in three model systems.

Kadyrov et al. reveal that the hypoxia sensing through HIF1A is an important regulator of monocyte-derived macrophage differentiation, which determines the extent of inflammation and cardiac remodeling after injury.

Ghobrial, Getz and colleagues characterize the changes in the tumor immune microenvironment associated with multiple myeloma progression.

Parasitic nematodes causing onchocerciasis and lymphatic filariasis rely on a bacterial endosymbiont, Wolbachia, which is a validated therapeutic target. Here, Clare et al. perform a high-throughput screen of 1.3 million compounds and identify 5 chemotypes with faster kill rates than existing anti-Wolbachia drugs.

A genome-wide association study identifies 17 genetic loci that are associated with the risk of myeloproliferative neoplasms (MPNs), and shows that the modulation of haematopoietic stem cell function drives MPN risk.

An improved, fully re-annotated Aedes aegypti genome assembly (AaegL5) provides insights into the sex-determining M locus, chemosensory systems that help mosquitoes to hunt humans and loci involved in insecticide resistance and will help to generate intervention strategies to fight this deadly disease vector.

The expansion of the genetic code with synthetic nucleotides has broadened our ability to evolve DNA as a functional material, but we lack analytical tools for the expanded alphabet. Here the authors demonstrate an enzyme-assisted method for the sequencing of six-letter DNA.

Torsional waves extend into the deep interior of Jupiter where they can modulate the outgoing heat flux and couple with Jupiter’s weather layer to generate the observed quasi-periodic oscillations in the cloud deck. Such waves can be used to explore the interior structure of gas giants.

RNA base-editors are often used in methods for RNA binding protein (RBP) target discovery. Here the authors present a new RBP target discovery method, PRINTER, and suggest optimal RNA base-editors for dual-RBP studies, emphasizing the importance of matching rBEs’ editing biases with RBPs’ binding preferences.

Functional MRI studies across ages show that the classic homunculus of the motor cortex in humans is in fact discontinuous, alternating with action control-linked regions termed the somato-cognitive action network.

Distinct cortical pyramidal neuron types, defined by developmental lineage, make unique contributions to behavioral decisions. We highlight the importance of interactions among diverse cortical and subcortical areas for successful decision outcomes.

A high-resolution kidney cellular atlas of 51 main cell types, including rare and previously undescribed cell populations, represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations.

The COVID-19 pandemic has stopped many human activities, which has had significant impact on emissions of greenhouse gases. Here, the authors present daily estimates of country-level CO₂ emissions for different economic sectors and show that there has been a 8.8% decrease in global CO2 emissions in the first half of 2020.

Poor access to suitable light-sheet microscopes remains a big obstacle for many end-users in biomedical research. Here, the authors present descSPIM, a low-cost, low-expertise light-sheet microscope for routine 3D imaging of cleared samples.

A variant of group A Streptococcus serotype M1 (UK) has been increasingly reported and can be differentiated from the global variant by its overexpression of the superantigen SpeA. Here, Davies et al probe the mechanism behind enhanced SpeA expression and demonstrate that a SNP in the 5’ leader sequence of ssrA is responsible for this virulence phenotype.

Respiratory syncytial virus enters cells by binding to cell-surface IGFR1, which activates PKCζ and induces trafficking of the NCL coreceptor to the RSV particles at the cell surface.

A phase 2 proof-of-mechanism trial shows that a κ-opioid receptor antagonist improves reward-related functioning in the brain and a clinical measure of anhedonia in patients with mood and anxiety disorders, serving as a model for implementing the ‘fast-fail’ approach to psychiatric treatment development.

New tumor epitopes are discovered by ribosome profiling and immunopeptidome mass spectrometry.

The sc-linker is an analysis framework that combines genome-wide association study summary statistics, epigenomics and single-cell transcriptomes to identify disease-critical cell types and cellular processes across tissues and states.

Wei and colleagues report that phosphorylation of Sin1 by S6K or Akt results in its dissociation from mTORC2, thus suppressing mTORC2 activity. A cancer-patient-derived Sin1 mutation that impairs this phosphorylation leads to mTORC2 hyperactivation and increased tumour formation in mice.

Stabilization of DNA quadruplex structures (G4) is lethal for cells with a compromised DNA repair pathway. Here, the authors show that CX-5461, a small molecule in clinical trials as RNA polymerase inhibitor, has G4-stablization properties and can be repurposed to target DNA repair-defective cancers cells.

The structure of the yeast nuclear pore complex, determined at sub-nanometre precision using an integrative approach that combines a wide range of data, reveals details of its architecture, transport mechanism and evolutionary origins.

The hunchback spider exhibits male-specific polymorphism in head shape. Here, the authors show that this polymorphism is determined by a large insertion that comprises duplicated male-specific genes including a duplicate of a key sexual differentiation regulatory gene.

An extensive survey to search for members of the only known Kuiper belt family, named after the parent body Haumea, found no family members fainter than absolute magnitude H_r = 7.9, significantly brighter than the detection limit (H_r = 9.5). This lack of small members is inconsistent with a catastrophic disruption as the origin of the Haumea family.

The design and optimisation of 3D DNA-origami can be a barrier to rapid application. Here the authors design barrel structure of stacked 2D double helical rings with complex surface patterns.

A positron emission tomography imaging tracer is developed to image mitochondrial function in vivo, and application of this tracer to a mouse model of lung cancer identifies distinct functional mitochondrial heterogeneity between tumour cells.

Soils may accumulate less carbon and with a slower turnover than Earth system models predict, according to analysis of the age distribution of global soil carbon, which finds that the mean age of soil carbon is older than that in simulated in models.

A genome-wide association meta-analysis study here shows novel genetic loci to be associated to body fat percentage, and describes cross-phenotype association that further demonstrate a close relationship between adiposity and cardiovascular disease risk.

Current approaches possibly cannot unambiguously distinguish the unique contributions of feedback inhibition versus feedforward inhibition to oscillatory events. Here authors show that a loss of CA1 pyramidal cell transmission, resulting in feedback inhibition reduction, leads to spatially triggered high-frequency oscillatory events; these events were like place cells in their spatial extent and localized to small regions in CA1.

Siliciano and colleagues describe the generation of bispecific antibodies that target the HIV-1 envelope protein (Env) on the surface of HIV-1-infected cells and the receptor CD16 on the surface of NK cells to induce the NK cell-mediated lysis of HIV-1-infected cells and reduce the viral reservoir.

Steven Aftergood weighs up a study that gauges the gap between oversight and the onward rush of innovation.