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Resting T cells are difficult to manipulate, and are a reservoir for latent HIV. Here, the authors develop a lipid nanoparticle formulation with the ability to transfect resting primary human T cells, enabling delivery of mRNAs that result in reactivation of latent HIV. This could help development of HIV cure strategies.

New Zealand implemented stringent COVID-19 control measures early after identification of its first case. Here, the authors perform whole genome sequencing of samples taken until 22 May 2020 and find high viral diversity indicative of multiple separate introductions and limited community transmission.

Data collected from more than 2,000 taxa provide an unparalleled opportunity to quantify how extreme wildfires affect biodiversity, revealing that the largest effects on plants and animals were in areas with frequent or recent past fires and within extensively burnt areas.

Two doses of the coronavirus disease 2019 vaccine ChAdOx1 nCoV-19 boost antibody responses and functions in phase 1/2 trial participants.

In this largest whole-exome sequencing study of epilepsies to date, the Epi25 Collaborative identified extremely rare variants that confer risk for diverse epilepsy subtypes, highlighting roles in synaptic transmission and neuronal excitability.

Genome-wide association meta-analyses identify 26 risk loci for epilepsy, including 19 loci specific to genetic generalized epilepsy. Prioritized candidate genes implicate synaptic processes and overlap with targets of antiseizure medications.

The mechanisms underlying epilepsy development are not well understood. Here the authors show that loss of a key component of the so called blood-brain barrier drives seizures in mice and is also lost in humans with treatment resistant epilepsy

Long COVID is a major public health issue since 2020 and exhibits frequent neurological symptoms. Greene et al. propose that brain fog results from leaky brain blood vessels and a hyperactive immune system, shedding light on this phenomenon.

Here, the authors perform a meta-analysis in 26,699 people with seizures and 492,324 controls to identify 25 genome-wide significant copy-number variants. The discovered loci point to known disease genes and associations with clinical annotations.

Cas12i is a genome editing platform with compact size that fits in AAV vector with short 43-mer gRNA, absence of tracrRNA, ability to process pre-crRNA, and high specificity. Here the authors present an unbiased mutational scanning approach to engineer Cas12i, which shows low activity in mammalian cells, and identify single substitutions that significantly improve indel activity.

Epilepsy is a brain network disorder with associated genetic risk factors. Here, the authors show that spatial patterns of transcriptomic vulnerability co-vary with structural brain network alterations in focal and generalized epilepsy.

Social science hypotheses suggest that humans prefer more equality in outcome distributions because the knowledge of inequality reduces the reward experience. Here, functional MRI was used to test directly for inequality-averse social preferences in the brain during monetary transfers between pairs of participants and an experimenter. The results indicate that the brain's reward circuitry is sensitive to distribution inequality and is actively modulated relative to context.

The PSA (KLK3) genetic variant rs17632542 is associated with reduced prostate cancer risk and lower serum PSA levels, although the underlying reasons are unclear. Here, the authors show that this PSA variant reduced proteolytic activity and leads to smaller tumours, but also increases invasion and bone metastasis, indicating its dual risk association depending on tumour context; the variant is associated with both lower risk and poor clinical outcomes.

Analysis of peatland carbon accumulation over the last millennium and its association with global-scale climate space indicates an ongoing carbon sink into the future, but with decreasing strength as conditions warm.

Claudin-5 is a component of tight junctions and has important roles in mediating the permeability of the blood-brain barrier. Campbell and co-workers administer short interfering RNA against claudin-5 in a model of brain injury, finding that it enhances water movement from the brain to the blood and alleviates swelling.

Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.

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A seismic event in northern Russia last month, interpreted by White House officials as a secret nuclear weapons test, was in fact a small earthquake, according to prominent US seismologists.

Seasonal influenza epidemics vary in timing and size, but the causes of the variation remain unclear. Here, the authors analyse a 15-year city-level data set, and find that fluctuations in climatic factors do not predict onset timing, and that while antigenic change does not have a consistent effect on epidemic size, the timing of onset and heterosubtypic competition do.

Epilepsies are common brain disorders and are classified based on clinical phenotyping, imaging and genetics. Here, the authors perform genome-wide association studies for 3 broad and 7 subtypes of epilepsy and identify 16 loci - 11 novel - that are further annotated by eQTL and partitioned heritability analyses.

Antigenic variants from human H1N1 and H3N2 influenza virus libraries possessing random mutations in the haemagglutinin protein, selected by incubation with human and/or ferret convalescent sera, identify escape variants similar to those that have emerged in nature.

In an effort by several research groups, a genome-wide RNAi-based screen presents a list of validated genes involved in cilia assembly and maintenance, and reveals previously unidentified ciliopathy factors.

Identifying selective tumor-associated molecules that can act as targets for T cells is a major goal of immunotherapy. Sewell and colleagues demonstrate that the nonclassical MHC molecule MR1 is expressed on a wide variety of cancer types and can be targeted by conventional T cells.

MIF is a cytokine best known for its modulatory effect on expression of proinflammatory cytokines. Here the authors show that MIF facilitates the NLRP3–vimentin interaction, resulting in Nlrp3 inflammasome activation.

Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.

Joseph Gleeson and colleagues identify CEP41 mutations as a cause of Joubert syndrome. Their functional studies suggest that CEP41 regulates ciliary entry of TTLL6, an enzyme required for tubulin glutamylation at the cilium.

Extreme heat is increasing in magnitude and frequency, threatening human health. This Review assesses mortality risk associated with extreme heat, revealing that human thermal tolerances (that is, uncompensable thresholds) were crossed for ~2% and 21% of global land area for young adults and older adults, respectively, from 1994 to 2023.

Paul Thompson and colleagues report a genome-wide association study for hippocampal, intracranial and total brain volume. They identify a locus at 12q24 associated with hippocampal volume and a locus at 12q14 associated with intracranial volume.

This study presents the crystal structures of three functional forms of diacylglycerol kinase, an integral membrane protein that catalyses a crucial step in oligosaccharide and lipopolysaccharide synthesis and assembly; these X-ray structures are markedly different from the only other structure available for this unique kinase that was solved using solution NMR.

Knowing how contaminant dissolved in rainfall will behave on its way through a catchment area has clear practical uses. One such study has been carried out in mid-Wales using an innocuous marker, the sodium chloride blown inland in sea spray. The authors find that a non-fractal input (in rainfall) is turned into a fractal output (in stream water). One conclusion is that contaminant flushing from a watershed will take more time than usually expected.

Efforts to control climate change require the stabilization of atmospheric carbon dioxide concentrations. An assessment of the trends in sources and sinks of atmospheric carbon dioxide suggests that the sinks are not keeping up with the increase in carbon dioxide emissions, but uncertainties are still large.

A reference genome from the coccolithophore Emiliania huxleyi is presented, along with sequences from 13 additional isolates, revealing a pan genome comprising core genes and genes variably distributed between strains: E. huxleyi is found to harbour extensive genetic variability under different metabolic repertoires, explaining its ability to thrive under a diverse range of environmental conditions.