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How to buy time.

Establishment and maintenance of appropriate cell size is a prerequisite for cells to function efficiently. Here, Kiriakopulos et al. reveal that the lncRNA CISTR-ACT maintains cell size across cell types in humans and mice by regulating cell morphogenesis genes in trans via guidance of the transcription factor FOSL2.

DNA double strand breaks can be repaired by several pathways leading to different genetic outcomes. Here, the authors define the interplay between the DNA damage response factors 53BP1-RIF1 and core non-homologous end joining factors on diverse repair outcomes.

Scott Jackson, Jeremy Schmutz, Phillip McClean and colleagues report the genome sequence of the common bean (Phaseolus vulgaris) and resequenced wild individuals and landraces from Mesoamerican and Andean gene pools, showing that common bean underwent two independent domestications.

Here, the authors describe biallelic loss-of-function variants in human SHARPIN in individuals with autoinflammation and immunodeficiency, termed sharpenia. They also successfully treat one of these individuals with TNF inhibitors.

Whole-exome analysis of individuals with developmental disorders shows that de novo mutations can equally cause loss or altered protein function, but that most mutations causing altered protein function have not yet been described.

Climate change is shifting species distribution globally. Here, the authors track four decades of changes in the thermal affinity of 1,817 marine species across European seas, showing that most communities have responded to ongoing ocean warming via increases of warm-water species or decreases of cold-water species.

Linked-read whole-genome sequencing reveals patterns of structural DNA variants that are specific to homologous recombination deficiency and can be used to distinguish between BRCA1- and BRCA2-deficient phenotypes.

Hematopoietic stem cell formation via the endothelial-to-hematopoietic transition is initiated by a complex rewiring of the aortic endothelium. Here the authors identify Meis1 as an early driver of hemogenic specification of this arterial endothelium.

Genomic analyses of human populations in the Pacific provide insights into the peopling history of the region and reveal episodes of biological adaptation relating to the immune system and lipid metabolism through introgression from archaic hominins and polygenic adaptation.

OP9 is a yet-uncultivated bacterial lineage found in anaerobic environments. Dodsworth et al. use single-cell genomics and metagenomics to construct two near-complete OP9 genomes, revealing a fermentative metabolism and supporting the designation of OP9 as candidate phylum 'Atribacteria'.

Developmental disorders (DDs) are more prevalent in males, thought to be due to X-linked genetic variation. Here, the authors investigate the burden of X-linked coding variants in 11,044 DD patients, showing that this contributes to ~6% of both male and female cases and therefore does not solely explain male bias in DDs.

An in vivo screen of small-molecule compounds to inhibit the mosquito-stage development of Plasmodium identified hits that can be incorporated into bed nets and led to effective parasite killing in the insect host.

Organoid modeling of human forebrain development reveals an opposite imbalance in excitatory neuron number in macrocephalic and normocephalic autistic probands, stemming from divergent expression of transcription factors driving cell fate.

Paediatric acute respiratory distress syndrome (pARDS) is associated with significant mortality and morbidity. Here the authors use single cell sequencing of tracheal aspirate samples from children with pARDS and characterise immune phenotypes and associations with infection stage and pathogen.

Cerebro–costo–mandibular syndrome, CCMS, is a severe human multiple malformation disorder. Here, the authors report that mutations in SNRPBdisrupt the normal regulation of alternative splicing at this gene, and in so doing, may be responsible for the development of CCMS.

The genetic basis of gastric cancer, the fourth most common cancer worldwide, remains poorly understood. Here, the authors sequence and analyse the exomes and transcriptomes of primary gastric tumours and cell lines, and identify a ZAK kinase isoform that may have an oncogenic role in gastric cancer.

Completion of genome sequences for the diploid Setaria italica reveals features of C₄ photosynthesis that could enable improvement of the polyploid biofuel crop switchgrass (Panicum virgatum). The genetic basis of biotechnologically relevant traits, including drought tolerance, photosynthetic efficiency and flowering control, is also highlighted.

An in vivo RNA interference screening strategy in glioblastoma enabled the identification of a host of epigenetic targets required for glioblastoma cell survival that were not identified by parallel standard screening in cell culture, including the transcription pause–release factor JMJD6, and could be a powerful tool to uncover new therapeutic targets in cancer.

ChIP–seq and CETCh–seq data are used to analyse binding maps for 208 transcription factors and other chromatin-associated proteins in a single human cell type, providing a comprehensive catalogue of the transcription factor landscape and gene regulatory networks in these cells.

Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds.

Analysis of a near-chromosomal genome assembly and transcriptome profiling of the Indian cobra identifies genes expressed in the venom glands. These data should help develop a new antivenom.

Genome assemblies of 13 domesticated and wild rice relatives reveal salient features of genome evolution across the genus Oryza, especially rapid species diversification and turnover of transposons. This study also releases a complete long-read assembly of IR 8 ‘Miracle Rice’.

Analysis of rare de novo mutations in gene regulatory elements suggests that 1–3% of patients with neurodevelopmental disorders carry such mutations in elements that are active in the fetal brain.

The Cancer Genome Atlas Research Network report integrated genomic and molecular analyses of 164 squamous cell carcinomas and adenocarcinomas of the oesophagus; they find genomic and molecular features that differentiate squamous and adenocarcinomas of the oesophagus, and strong similarities between oesophageal adenocarcinomas and the chromosomally unstable variant of gastric adenocarcinoma, suggesting that gastroesophageal adenocarcinoma is a single disease entity.

Conditional expression of the most common somatic gain-of-function Ezh2 mutation in mouse models of melanoma and lymphoma reveals insight into its cooperation with other oncogenic events and its effects on the epigenome.

Somasekar Seshagiri, James Brugarolas and colleagues report the mutational landscape of 167 non–clear cell renal cell carcinomas (nccRCCs) from multiple subtypes. They identify subtype-specific driver mutations and gene fusions, including ones involving MITF, which result in expression of the anti-apoptotic protein BIRC7 and might thus indicate candidates for treatment with BIRC7 inhibitors.

Environmental adaptation is generally studied at the genomic level, but it may also be driven by transcriptional processes. Here, the authors investigate variation in gene expression and RNA editing across diverging populations of Drosophila melanogaster from two microclimates.

Heather Mefford, Ingrid Scheffer and colleagues report targeted resequencing of 47 genes in 500 individuals with epileptic encephalopathies. They identify pathogenic mutations in 11% of their cohort and show that de novo mutations in CHD2 and SYNGAP1 cause epileptic encephalopathy.

Zhu et al. discover that in human brain there is widespread anatomic distribution of low-frequency somatic, mosaic L1 insertions, using deep whole-genome sequencing of neuronal and glial fractions and machine-learning analysis.

Chromodomain Helicase DNA-binding (CHD) proteins have been implicated in neurodevelopmental processes. Here, the authors identify missense variants in CHD3 that disturb its chromatin remodeling activities and cause a neurodevelopmental disorder with macrocephaly and speech and language impairment.

Micro- and nannofossil, trace fossil and geochemical evidence from the Chicxulub impact crater demonstrates that proximity to the asteroid impact site did not determine rates of recovery of marine ecosystems after the end-Cretaceous mass extinction.

New antimalarials are urgently needed. Here, the authors identify Open Source Malaria compound, OSMS-106, as a reaction hijacking inhibitor of the malaria parasite protein synthesis machinery, with potential use for treatment and prophylaxis.

Most of the more than 200 known genetic risk loci for inflammatory bowel disease (IBD) reside in regulatory regions. Here, the authors provide eQTL datasets for six circulating immune cell types and ileal, colonic and rectal biopsies to map regulatory modules and identify potential causative genes for IBD.

Novel antimalarial drugs are urgently needed to combat parasite drug resistance. Here, Vaidya et al. describe a new chemical class of potent antimalarial compounds that act by disrupting the parasite's sodium homeostasis.

Nada Jabado and colleagues report identification of gain-of-function mutations in ACVR1, which encodes activin A receptor type I, in midline pediatric high-grade astrocytomas.

In parts of southeast Asia, malaria parasites are showing resistance to the active ingredient in artemisinin-based antimalarial drugs. Delineation of a cell-signalling pathway might help to explain this phenomenon. See Letter p.683

The antimalarial mefloquine has been used in the clinic for decades, yet its mode of action has remained elusive. Now, a study reports that the enantiomer (+)-mefloquine binds to the cytosolic ribosome of the major malaria parasite Plasmodium falciparum.

N⁶-methyladenosine (m⁶A) is prevalent at RNA:DNA hybrids in human pluripotent stem cells. The m⁶A reader YTHDF2 interacts with R-loop-enriched loci in dividing cells, and YTHDF2 loss leads to increased R-loop levels and accumulation of γH2AX.

Steroid units can facilitate membrane permeation and bioavailability in drugs. Here, using a medicinal chemistry program, Krieget al. identify an arylmethylamino steroid that kills Plasmodium parasites, likely through a chelate-based quinone methide mechanism, and has activity against Schistosoma mansoni.

John Chambers and colleagues report a genome-wide association study for type 2 diabetes in individuals of south Asian ancestry. They identify six loci newly associated with type 2 diabetes.

Genome-wide meta-analysis, fine-mapping and integrative prioritization using expression quantitative trait loci, protein interaction networks and tissue-specific expression implicate new candidate susceptibility genes for Alzheimer’s disease.

Matthew Hurles, David FitzPatrick and colleagues report the discovery of four novel Mendelian disorders based on their analysis of exome sequence data from 4,125 families with diverse rare developmental disorders. They present their analytical pipeline as a general strategy for the discovery of genetic causes of autosomal recessive disorders.

Large-scale sequencing of coding exons of MRAP2 in 9,418 adults and adolescents identifies loss-of-function mutations that are associated with monogenic obesity, hypertension and hyperglycemia.

Matthew Hurles and colleagues report exome sequencing of 1,891 individuals with syndromic or nonsyndromic congenital heart defects (CHD). They found that nonsyndromic CHD patients were enriched for protein-truncating variants in CHD-associated genes inherited from unaffected parents and identified three new syndromic CHD disorders caused by de novo mutations.

Marshall Horwitz, Charles Mullighan, Kenneth Offit and colleagues report the identification of a recurrent germline PAX5 mutation in families with pre–B cell acute lymphoblastic leukemia. They also identify sporadic cases of this leukemia with the same mutation that arose somatically.