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The structural anisotropy necessary for the powered directional rotation of chemically fuelled molecular motors had previously been provided by chiral fuels or enzymes. Now it has been shown that asymmetry in the organocatalyst itself is sufficient for directional fuelled rotation. This informs how chemical energy is transduced through catalysis, the fundamental process that powers biology.

The E6 oncoprotein derived from tumour-associated human papillomaviruses (HPVs) binds to and induces the degradation of the cellular tumour-suppressor protein p53. A common polymorphism that occurs in the p53 amino-acid sequence results in the presence of either a proline or an arginine at position 72. The effect of this polymorphism on the susceptibility of p53 to E6-mediated degradation has been investigated and the arginine form of p53 was found to be significantly more susceptible than the proline form. Moreover, allelic analysis of patients with HPV-associated tumours revealed a striking overrepresentation of homozygous arginine-72 p53 compared with the normal population, which indicated that individuals homozygous for arginine 72 are about seven times more susceptible to HPV-associated tumorigenesis than heterozygotes. The arginine-encoding allele therefore represents a significant risk factor in the development of HPV-associated cancers.

The authors find that TDP-43 loss of function—the pathology defining the neurodegenerative conditions ALS and FTD—induces novel mRNA polyadenylation events, which have different effects, including an increase in RNA stability, leading to higher protein levels.

TDP-43 dysfunction in ALS/FTD causes faulty splicing of the KCNQ2 ion channel, leading to toxic protein buildup, neuron hyperactivity and a potential new biomarker and treatment target using RNA-based therapies.

Therapeutic proteins are often conjugated with polymers, but separating the conjugate from unconjugated protein and free polymer is a major challenge. Here, the authors discover that proteins conjugated to charged or zwitterionic polymers maintain solubility in 100% ammonium sulfate, greatly simplifying purification.

Insulin stimulates TUG cleavage to translocate GLUT4 and enhance glucose uptake. Here Bogan and colleagues show that the TUG cleavage product regulates thermogenic gene transcription, thereby coupling glucose uptake to organismal energy expenditure.

Now that the Intergovernmental Panel on Climate Change has spoken more clearly than ever — and policymakers are listening — it may be time to take a new direction. Amanda Leigh Haag reports on suggested ways forward.

Over half the world’s rivers dry periodically, yet little is known about the biological communities in dry riverbeds. This study examines biodiversity across 84 non-perennial rivers in 19 countries using DNA metabarcoding. It finds that nutrient availability, climate and biotic interactions influence the biodiversity of these dry environments.

Risk variants for ALS and FTD in the synaptic gene UNC13A increase the expression of an UNC13A cryptic exon in neurons with TDP-43 depletion.

Reconstitution experiments using substrates prepared by chemoenzymatic synthesis demonstrate that three LCP family proteins catalyze the ligation of wall teichoic acids to peptidoglycan in the biosynthesis of the Staphylococcus aureus cell wall.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

The mechanisms governing cholesterol homeostasis remain incompletely understood. Here, the authors develop an integrative genomic strategy to identify MMAB, and enzyme in the adenosylcobalamin pathway, as a regulator of hepatic LDLR activity and cholesterol biosynthesis.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

A molecular machine that can be programmed to position a substrate at one of two directing sites on a molecule, which control the stereochemistry of addition to the substrate, demonstrates complexity, precision and function previously only observed in nature.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

The authors characterized puncta in the ASC complex by correlative light microscopy and cryo-ET in cells and propose an ultrastructure of the ASC filament network.

Distant metastasis is a major reason for mortality in patients with prostate cancer (PC). Here, the authors show that receptor-interacting protein kinase 2 (RIPK2) stabilizes c-Myc and its targeting impairs PC metastasis development.

Heymut Omran, Joseph LoTurco and colleagues show that mutations in the dyslexia susceptibility candidate gene DYX1C1 cause primary ciliary dyskinesia. Their functional studies suggest that DYX1C1 is required for the cytoplasmic preassembly of axonemal dynein complexes.

An apparent redundant role with EZH2 has rendered EZH1 as a secondary player in PRC2-mediated homeostasis regulation. Here, the authors report that gain- and loss-of-function variants in EZH1 cause neurodevelopmental disorders, highlighting its functional relevance.

A composite knot with nine crossings of the same handedness has been prepared from a hexameric circular helicate in 41% yield in a two-step synthesis. An isomeric cyclic [3]catenane topologically constrained to always have at least three twists within the links is also formed. Both topologies have a high degree of writhe, analogous to that of supercoiled DNA.

Generating human stem cells from a single cell recovered during preimplantation genetic diagnosis does not, in principle, harm the embryo. Can the approach be used in assisted reproductive technology programmes?

Nature assesses the aftermath of a series of nanotechnology-lab bombings in Mexico — and asks how the country became a target of eco-anarchists.

Bacteria often produce antimicrobial toxins to compete in microbial communities. Here, the authors identify a family of peptide toxins that are produced by, and target, Bacteroidetes species, some of which are widespread in the human gut microbiota.

Pulmonary fibrosis is a major public health problem with unclear mechanism and limited therapeutic options. Here the authors show that a fibroblast-enriched endoplasmic reticulum protein, TXNDC5, promotes pulmonary fibrosis by stabilizing TGFBR1 and show the potential of TXNDC5 as a therapeutic target against pulmonary fibrosis.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Aberrant changes in DNA methylation have been implicated in various neurodevelopmental disorders but remain under studied in developmental and epileptic encephalopathies. Here, the authors demonstrate the diagnostic utility of genome-wide DNA methylation analyses toward identifying molecular etiologies in developmental and epileptic encephalopathies.

Including participants from 45 countries, Bago et al. find that the situational factors that affect moral reasoning are shared across countries, with diminished observed cultural variation.

Sarcomatoid and rhabdoid tumours are highly aggressive forms of renal cell carcinoma that are also responsive to immunotherapy. In this study, the authors perform a comprehensive molecular characterization of these tumours discovering an enrichment of specific alterations and an inflamed phenotype.