Search

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).

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.

Australian archaeological finds of 12,000-year-old fireplaces and artefacts match nineteenth-century GunaiKurnai ritual practices. They represent approximately 500 generations of cultural transmission of this ritual.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

A streamlined synthesis of β-arylethylamines using two distinct copper catalysts is reported, and an azide anion is proposed to both react to form the product and facilitate catalyst regeneration.

Turley and colleagues find that Gremlin1-expressing lymph node fibroblastic reticular cells support dendritic cell homeostasis via provision of FLT3L.

By regulating the level of accessible cholesterol on endothelial cells via OSBP/ORP-mediated transport, tetraspanin tunes the balance of Cdc42 and RhoA activities to affect vascular inflammation. Reducing accessible cholesterol by statin treatment or blocking its non-vesicular transport by OSBP/ORP inhibition can limit vascular inflammation.

An expert-elicitation process identifies current methodological barriers for monitoring terrestrial biodiversity, and how technological and procedural development of robotic and autonomous systems may contribute to overcoming these challenges.

Dopaminergic action prediction error signals are used by mice as a value-free teaching signal to reinforce stable sound–action associations in the tail of the striatum.

Hesitation—pausing in the face of uncertainty—is ubiquitous in daily life and disrupted in several psychiatric disorders. Unlike other forms of response inhibition, hesitation is mediated by indirect, but not direct, pathway striatal neurons.

Pulmonary large cell neuroendocrine carcinoma is an aggressive subtype of lung cancer. Here, the authors identify distinct subtypes based on genomic alterations and transcriptomic alterations.

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.

The model archaeon Sulfolobus acidocaldarius produces several protein filaments with specialised functions, including flagellum-like archaella, Aap pili, and adhesive threads. Here, the authors describe high-resolution structures and distinct glycosylation patterns for the three filaments, and present an integrated model of the filaments in the context of the S-layer.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Pathogenic variants of DDX3X are associated with neurodevelopmental disorders (NDD) and cancer. Here, the authors perform saturation genome editing of DDX3X to test the functional impact of 12,776 variants, develop a machine learning classifier to identify variants relevant for NDD, and show that DDX3X predominantly acts as a tumour suppressor in cancer.

The basal-plane surfaces of hexagonal close-packed crystals typically exhibit an alternating sequence of A and B steps with different atomic structures and growth kinetics. Here the authors demonstrate a method to determine whether A or B steps have faster kinetics under specific growth conditions.

Here the authors evaluate neutralizing antibodies following COVID-19 bivalent vaccination and find that both Pfizer BA.5 (BNT162b2) and Moderna BA.1 (mRNA-1273) vaccines elicit similar neutralization against Omicron subvariants BA.1, BA.5, BQ.1.1, and XBB.1.5 in patients with end-stage kidney disease.

In situ measurements based on coherent X-ray spectroscopy are performed during the epitaxial growth of gallium nitride films, revealing a memory effect in the arrangement of islands formed on successive crystal layers.

Single-cell transcriptomic profiling of fetal liver, skin, kidney and yolk sac reveals the differentiation trajectories of human haematopoietic stem cells and multipotent progenitors, which are validated to produce an integrated map of fetal liver haematopoiesis.

TDP-43 gains function due to perturbed autoregulation in a Tardbp knock-in mouse model of ALS-FTD, leading to aberrant Mapt splicing and a paucity of parvalbumin interneurons. Phenotypic heterogeneity is exploited to yield modifiers of disease.

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.

Machine learning has the potential to significantly speed-up the discovery of new materials in synthetic materials chemistry. Here the authors combine unsupervised machine learning and crystal structure prediction to predict a novel quaternary lithium solid electrolyte that is then synthesized.

Translational regulation of isoforms in the developing nervous system is not well understood. Here, the authors report translational de-repression of RNA binding protein isoforms at their 5′UTRs in the neocortex and show the neurodevelopmental risk of post-transcriptional dysregulation.

Irreversible bond formation in covalent organic frameworks leads to amorphous materials. Here, the authors show that crystalline and ultra-stable covalent amide frameworks can be accessed by devitrification of amorphous polyamide networks.

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.

In a multicenter, single-arm, open-label phase 2 study of patients with previously treated metastatic uveal melanoma, treatment with tebentafusp, a soluble TCR bispecific (gp100xCD3) showed promising clinical activity with an acceptable safety profile.

Treatment of SHIV-infected monkeys with potent broadly neutralizing anti-HIV-1 monoclonal antibodies resulted in rapid control of viral replication in both peripheral blood and tissues; viral rebound was linked to decreasing antibody concentrations and not the generation of escape mutations, and setpoint viral load following viral rebound remained lower than the initial baseline viral load.

Storm severity indices of European winter storms in climate models show future increased storm losses in northwestern Europe, caused by changes in the location and intensity of storms, and increasing population.

Activation of the transcription factor IRF3 is a key event in antiviral responses. Lichty and colleagues show that recruitment of the mTOR downstream effector S6K1 to the STING-TBK1 signaling complex is required for the activation of IRF3 after infection with DNA viruses.

Predicted sea-level rise is widely anticipated to lead to increased coastal erosion, however, assessing how rocky coasts will respond to changes in marine conditions is difficult to constrain. Here, the authors find that a North Yorkshire rocky cliff has been eroding at a similar rate over the last 7 kyr, and they do not observe an increase in erosion rates in response to modern sea level rise.

Two decades after antisense oligonucleotides (ASOs) were initially identified as agents capable of modulating RNA processing and protein expression, the first antisense oligonucleotide (ASO) therapies have now been approved for the treatment of neurological disease. Here, Rinaldi and Wood discuss our current understanding of ASO pharmacology, and the future prospects for ASO-mediated treatment of neurological disease

The development of effective therapies for neuromuscular disorders is hampered by considerable challenges, including the abundance of skeletal muscle within the body and the multisystemic nature of many of these diseases. Here, Muntoni and Wood review recent advances in the development of novel therapies that target RNA, which are exemplified by three disorders: Duchenne muscular dystrophy, myotonic dystrophy and spinal muscular atrophy.

Could this be the year that AI is going to surpass human performance in playing the popular video game Angry Birds? The organizers of the annual AIBIRDS competition discuss the challenges involved.