Search

The study of learning algorithms in the neocortex requires comprehensive knowledge of synaptic plasticity between its diverse cell types, which is currently lacking. Chindemi et al. describe a modeling approach to fill these gaps in experimental literature, and predict the features of synaptic plasticity in vivo.

Here, the authors leverage whole-genome sequencing from >88,000 diverse individuals to uncover 18 BMI-related genetic signals, including novel variants in participants of African genetic ancestry, highlighting the value of diversity in genetic discovery.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Rodriguez et al. define a native role for RAN translation and CGG repeats in regulating mGluR-dependent fragile X protein (FMRP) synthesis. RAN-blocking antisense oligonucleotides increase FMRP and improve survival of neurons from patients with repeat expansions.

The impact of the DART spacecraft on the asteroid Dimorphos is reported and reconstructed, demonstrating that kinetic impactor technology is a viable technique to potentially defend Earth from asteroids.

Here the authors show that the disruption of OGT expression in mouse embryonic stem cells unleashes TET activity, causing genome-wide decreases in DNA methylation and increases in 5-hydroxymethylcytosine, leading to the derepression of transposable elements and, in certain cases, the activation of nearby genes.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

Analysing camera-trap data of 163 mammal species before and after the onset of COVID-19 lockdowns, the authors show that responses to human activity are dependent on the degree to which the landscape is modified by humans, with carnivores being especially sensitive.

In two independent cohorts of Ugandan children with severe malaria, elevated blood uric acid was found to be common and linked to both acute and postdischarge mortality, as well as poorer long-term cognitive outcomes.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

Genomic studies often lack representation from diverse populations, limiting equitable insights. Here, the authors show that the BIG Initiative captures extensive genetic diversity and reveals ancestry-linked health disparities in a community-based Mid-South cohort.

Detection of resistance to the antibiotic metronidazole in C. difficile often requires the presence of heme in the media, for unclear reasons. Here, the authors show that most metronidazole-resistant strains carry a mutation that promotes expression of a heme-dependent enzyme that degrades nitroimidazoles, and the mutation often co-occurs with an amino-acid substitution in DNA gyrase that confers resistance to another class of antibiotics, fluoroquinolones.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

TDP-43 controls an exon splicing event in UNC13A that results in the inclusion of a cryptic exon associated with frontotemporal dementia and amyotrophic lateral sclerosis.

Stroke is a multifactorial disease influenced by genetic and environmental factors. Here, the authors apply exome-wide association analysis to find rare coding variants associated with stroke in a Pakistani cohort, finding a significant association of a variant in NOTCH3 that is highly enriched in South Asians.

Social inequalities may be reflected in how ecosystem services are distributed among groups of people. Here the authors estimate the distribution of three ecosystem services across demographic and socioeconomic groups in the US between 2020 and 2100, finding that non-white and lower-income groups disproportionately bear the loss of ecosystem service benefits.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

Clouds on Titan result from the condensation of methane and ethane and, at present, cloud activity mainly occurs in the southern hemisphere; general circulation models predict that this distribution should change with the seasons on a 15-year timescale. Now, global spatial cloud coverage on Titan is reported to be in general agreement with the models.

Durable agonism of NPR1 achieved with a novel investigational monoclonal antibody could mirror the positive hemodynamic changes in blood pressure and heart failure identified in humans with lifelong exposure to NPR1 coding variants.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

One of the major causes of cancer-related mortality is represented by metastatic lung cancer. Here the authors characterize the role of TMEM106B in driving metastatic lung adenocarcinoma and suggest that TMEM106B-mediated secretion of cathespin impacts cell migration and invasion of lung cancer cells, increasing metastatic spreading.

The calvarial stem cell niche is populated by a cathepsin K-expressing cell lineage and a newly identified discoidin domain-containing receptor 2-expressing lineage, both of which are required for proper calvarial mineralization.

Most genome-wide association studies assume an additive model, exclude the X chromosome, and use one reference panel. Here, the authors implement a strategy including non-additive models and find that the number of loci for age-related traits increases as compared to the additive model alone.

A dataset of coding variation, derived from exome sequencing of nearly one million individuals from a range of ancestries, provides insight into rare variants and could accelerate the discovery of disease-associated genes and advance precision medicine efforts.

Anterior Uveitis is a common inflammatory eye disease that can result in vision loss. Here, the authors perform GWAS and whole-exome analyses of Anterior Uveitis to identify the underlying genetics of HLA-B*27 positive and negative forms of the disease.

Longitudinal genomic and transcriptomic profiling of 1,143 patients with multiple myeloma by the Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study yields an improved copy number and gene expression subtype scheme, most notably a high-risk proliferative subtype associated with complete loss of RB1 or MAX.

An exome-wide association study of six smoking phenotypes in up to 749,459 individuals identifies associations of rare coding variants in CHRNB2 that may reduce the likelihood of smoking.

Structural variants in more than 17,000 human genomes are mapped and characterized using whole-genome sequencing, showing how this type of variation contributes to rare deleterious coding and noncoding alleles.

Genome-wide meta-analysis of SARS-CoV-2 susceptibility and severity phenotypes in up to 756,646 samples identifies a rare protective variant proximal to ACE2. A 6-SNP genetic risk score provides additional predictive power when added to known risk factors.