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The control of off-target activity is a challenge for adapting CRISPR to therapeutic use. Here the authors present CRISPECTOR, a software tool to detect, evaluate and quantify editing activity, including translocations, from NGS data.

Questions have arisen as to whether patients with severe COVID-19 disease can generate a T cell response against SARS-CoV-2. Tao Dong and colleagues report that convalescent patients with COVID-19 harbor functional memory CD4⁺ and CD8⁺ T cells that recognize multiple epitopes that span the viral proteome. CD4⁺ T cells predominated the memory response in patients with severe disease, whereas higher proportions of CD8⁺ T cells were found in patients with mild disease.

Modulation of metabolic pathways is linked to regulation of immune cells including macrophages. Here the authors identify a role for CD1d in the metabolic rewiring of macrophages, which alters responsiveness to innate stimuli.

Deep brain stimulation programming for Parkinson’s disease entails the assessment of a large number of possible simulation settings, requiring numerous clinic visits after surgery. Here, the authors show that patterns of functional MRI can predict the optimal stimulation settings.

Global megafaunal extinctions took place in the late Quaternary, yet the relative impact of climate and humans in the faunal collapse is unclear. Here, the authors show that megafaunal extinctions in Australia were independent of climate variability and took place approximately 13,500 years after human arrival.

Immunity to one serotype of dengue virus can worsen disease following exposure to another serotype, a process called ‘antibody-dependent enhancement’. Grimes and colleagues characterize the function and structural basis of an unusual, potent and broadly neutralizing antibody that lacks such activity.

We have developed an automated and high-throughput, three-dimensional, vision-controlled inkjet deposition process that enables the high-resolution, contactless printing of a range of materials with varying elastic moduli to create complex structures and robots.

The impact of prior infection on the immune response to COVID-19 vaccination has not been fully characterised. Here, the authors use data from ~100,000 adults in the UK and find that a single vaccine dose in those with prior infection produces a comparable or stronger response to two doses in those without infection.

Magnetic skyrmions are promising objects for future spintronic devices. However, a better understanding of their dynamics is required. Here, the authors show that in contrast to predictions the skyrmion Hall angle is independent of their diameter and motion is dominated by disorder and skyrmion-skyrmion interactions in the system.

Piccione et al find evidence for Antarctic ice sheet instability driven by millennial cycles in Southern Ocean temperature, providing clues for the mechanisms that link climate change and rapid Antarctic ice loss events.

Systematic comparison of SARS-CoV-2 spike proteins from pre- and post-Omicron variants in cell lines, primary respiratory epithelial cells and Syrian hamsters show distinct phenotypic trajectories in replication kinetics, cell tropism, cell-to-cell fusion, spike processing, cell entry routes and virulence.

Allosteric control of metabotropic glutamate receptor is of therapeutic value in the treatment of neurological disorders. Here, using cryoEM, the authors describe the diversity of positive allosteric modulation on the metabotropic glutamate receptor, mGlu₅.

Climate sensitivity in the late Miocene was comparable to the late Pleistocene and twenty-first century, with cooling at the time coupled to declining carbon dioxide, according to a CO₂ record determined from boron isotopes in planktic foraminifera

Decisions on where to source nickel for use in low-carbon technologies must consider the biomass losses caused by mining. This study found that, in many cases, these unaccounted emissions were significant relative to other Scope 1 and Scope 2 emissions from nickel extraction and processing.

It is generally accepted that declining carbon dioxide (CO₂) levels were an important factor in the Eocene–Oligocene transition about 34 million years ago, when the world shifted from a greenhouse to an icehouse climate. Here, using the boron isotope pH proxy on carbonate microfossils from a recently discovered geological section in Tanzania, atmospheric CO₂ levels before, during and after the climate transition are estimated.

Researchers developed an accurate model to analyse bivalent antibody binding. By analysing many SARS-CoV-2-specific antibodies, they found that their molecular reach can predict their neutralisation potency.

Evolutionary theory predicts that trade-offs between traits are pervasive, yet they are rarely observed in experimental evolution. Dense sampling and precise measuring of performance of adaptive mutations in evolving yeast shows that while many such mutations result in modest improvements in multiple traits, the totality of the data reveals the existence of trade-offs even during initial adaptation.

Current thinking on the causes of anthropogenic radiative forcing in the lower atmosphere is misleading. This study finds tropospheric ozone-precursor emissions have contributed more to positive forcing, and halocarbons more to negative forcing, than previously thought.

Phylogenetic comparative methods applied to datasets of body size in five major vertebrate clades show that rates of speciation and morphological evolution are positively related at broad macroevolutionary scales but with heterogeneity in the strength and direction of these associations at finer scales.

Evolutionary analysis of swine-origin H1N1 influenza A virus provides evidence that it was derived from several viruses circulating in swine and that it possesses genes from avian, swine and human origin. Furthermore, transmission to humans may have occurred several months before recognition of the current outbreak.

Caenorhabditis nematodes are important model organisms. Here, the authors report the biology and genome of Caenorhabditis inopinata, a first sibling species of C. elegans, and develop genetic and molecular techniques for C. inopinata.

Respiratory infections occur throughout life but how this shapes the lung immune system through time is unclear. Wack and colleagues show that a previous influenza infection recruits monocytes to the lung, which then assume an alveolar macrophage-like phenotype and mediate long-term antibacterial protection.

Following global DNA demethylation, mouse gonadal primordial germ cells undergo remodelling of repressive chromatin modifications, resulting in a sex-specific signature that is required to safeguard the transcriptional program.

Immune checkpoint therapies (ICT) are promising for treating various cancers, but response rates vary. Here the authors show, in mouse models, that tumor-infiltrating mast cells colocalize with regulatory T cells, coincide with local reduction of MHC-I and CD8 T cells, and is associated with resistance to ICT, which can be reversed by c-kit inhibitor treatment.

Li et al. analyzed structural connectivity of deep brain stimulation electrodes in 50 patients suffering from obsessive-compulsive disorder operated at four centers. Connectivity to a specific tract within the anterior limb of the internal capsule was associated with optimal treatment response across cohorts, surgeons and centers.

Four genome-wide associated loci are currently known for malaria susceptibility. Here, the authors expand on earlier work by combining data from 11 malaria-endemic countries and additional population sequencing informing an African-enriched imputation reference panel, with findings including a previously unreported association on chromosome 6.

Understanding the immune response to SARS-CoV-2 is dependent on being able to distinguish COVID-19 immune responses from cross-reactive immune responses to other coronaviruses. Here the authors show that choice of antigens and whether an ICS, ELISPOT or T cell proliferation assay is used has a major effect on this discriminatory ability.

Deep-learning models for the automated measurement of retinal-vessel calibre in retinal photographs perform comparably to or better than expert graders in associations of measurements of retinal-vessel calibre with cardiovascular risk factors.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

A large study in the United Kingdom shows that virus-specific antibody levels associated with at least 67% protection against SARS-CoV-2 Delta variant infection last longer after two doses of BNT162b2 vaccine than after two doses of ChAdOx1 vaccine in previously uninfected individuals.

The duration and strength of protection against SARS-CoV-2 infection resulting from a booster vaccine dose or breakthrough infection are not well understood. This study uses data from the UK COVID-19 Infection Survey to investigate correlates of protection against Omicron BA.4/5 infection and assess antibody responses to booster vaccination and breakthrough infections.

Loss of function polymorphisms of phospholipase D3 and D4 are associated with inflammatory diseases and their function is unclear. Here the authors show that PLD3/4 function as RNAses and deletion of these proteins in mice leads to accumulation of ssRNA which exacerbates inflammation through TLR signalling.

Dynamic mass photometry allows label-free tracking and mass measurement of individual membrane-associated proteins diffusing on supported lipid bilayers. The approach can be used to monitor dynamic (dis)assembly of protein complexes.

The tumour microenvironment (TME) may change in response to cancer treatments such as KRAS G12C inhibition, with potential implications for combination therapies. Here, the authors provide an antibody panel and workflow for analysing the TME with imaging mass cytometry in pre-clinical mouse models.

Developmental duration is a key life-history trait. Cooney et al. compile data on 3096 bird species to quantify the degree to which phylogenetic history, body size and ecological variables like predation risk or breeding phenology influence variation in developmental duration.

Label-free, spatio-temporal imaging of cellular physiological responses is challenging. Here the authors combine digital holographic microscopy with a millifluidic chip and mathematical modelling to quantify cell volume, mass and cell uptake under changing environmental conditions.

A new inhibitor of Mycobacterium tuberculosis leucyl-tRNA synthetase is associated with bactericidal activity in humans and may be a candidate for combination therapy of tuberculosis.

Glyphosate is the world’s most widely-used herbicide. Here, Belbin et al. show that plant responses to glyphosate, and therefore herbicide activity, depend on plant circadian rhythms suggesting that considering the time-of-day of application could lead to more efficient agrochemical use.

One of two papers showing that inhibition of Dll4-mediated Notch signalling inhibits tumour growth by deregulation of tumour angiogenesis.

Immunotherapies have shown limited efficacy in patients with glioma. Here, based on an in vivo kinome knockout CRISPR screen, the authors show that checkpoint kinase 2 promotes CD8 T cell immune evasion and that its depletion or inhibition improve survival and response to PD1/PDL1 blockade in preclinical glioma models.