Search

Saito et al. identify sphingosine kinase 1 as a critical regulator of physiological ductus arteriosus closure and pathological supravalvular aortic stenosis through its role in smooth muscle cell proliferation and propose potential therapeutics.

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 construction of porous solids from discrete organic molecules usually involves the formation of regular porous crystals. In this study, a covalent scrambling reaction gives molecules with a range of shapes that do not pack effectively — manipulation of the reagent ratio allows fine control of porosity.

The fabrication self-sorting supramolecular gels, containing co-existing homomolecular assemblies with similar physical and chemical properties, is challenging. Here pH-controlled self-sorting gelators are reported, where the order of assembly of each component is predetermined by gelator pK_a.

Porous materials are technologically important for a wide range of applications, such as catalysis and separation. Covalently bonded organic cages can now be assembled into crystalline microporous materials, and their porosity is found to be intrinsic to their molecular cage structure.

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).

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.

Multicomponent supramolecular hydrogels have been prepared using a self-sorting mixture of two different gelators—one of which is photosensitive. Irradiation of the gels through a mask leads to the photosensitive network being selectively removed by a light-triggered gel-to-sol transition in a process that can be used to produce patterned gels with spatially controlled properties.

A stiff hydrogel gel is presented that encapsulates and stabilizes proteins without additives or excipients and uses mechanical strain to release them, offering low-cost and versatile delivery of therapies.

Molecular solar thermal energy storage (MOST) systems employ photoswitchable molecules that absorb sunlight and store energy through reversible isomerization, cyclization or other intramolecular rearrangements. Here, the authors introduce a micellar solar thermal energy storage (MIST) system, utilizing micellar aggregates based on azobenzene-functionalized dipeptide amphiphiles to achieve extended energy storage durations, offering water-compatible formulations and improved processability for sustainable energy applications.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

Kinetic trapping in supramolecular gels leads to varied morphologies and macroscopic properties. Emily R. Draper and Dave J. Adams discuss subtle experimental effects that can lead to reproducibility issues in these systems.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

Dynamic supramolecular systems can be designed to adapt phases in a pre-programmable way. Here the transient nature of a gel system is exploited, in combination with the application of mechanical stimuli, to obtain soft materials with aligned fibres in a controllable way.

Petrels are wide-ranging, highly threatened seabirds that often ingest plastic. This study used tracking data for 7,137 petrels of 77 species to map global exposure risk and compare regions, species, and populations. The results show higher exposure risk for threatened species and stress the need for international cooperation to tackle marine litter.

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.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Nanosensors of the activity of the protease granzyme B, which release a cleaved fluorescence reporter that filters into urine, enable the early diagnosis of acute transplant rejection in mice.

The internal core antigen, p24, of HIV performs differing roles at various stages in the viral life cycle. The structure of the protein has now been solved allowing an informed view of its role in isolation and as a domain within the precursor virion structural protein Gag p55.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Self-sorting events in supramolecular assembly lead to complex systems that are attractive for the design of functional materials, but have remained difficult to understand and control. Now, the growth of self-sorted supramolecular nanofibres has been elucidated by direct imaging through real-time in situ confocal microscopy.

The full extent of the genetic basis for hearing impairment is unknown. Here, as part of the International Mouse Phenotyping Consortium, the authors perform a hearing loss screen in 3006 mouse knockout strains and identify 52 new candidate genes for genetic hearing loss.

Identification and characterization, using a comprehensive embryonic phenotyping pipeline, of 410 lethal alleles during the generation of the first 1,751 of 5,000 unique gene knockouts produced by the International Mouse Phenotyping Consortium.

Hydrogels are hydrated polymer networks with applications in biotechnology and medicine. When created from alpha-helical peptides with engineered peptide sequences, their formation mechanisms can be controlled, leading to diverse properties. For instance, those with hydrogen-bonded networks melt on heating, but those formed through hydrophobic interactions strengthen when warmed.

DEK is a secreted protein abundant in the synovia of patients with juvenile idiopathic arthritis. Here the authors show DEK is important for neutrophil extracellular trap formation and joint inflammation, and demonstrate therapeutic efficacy of DEK-targeting aptamers in a mouse model of arthritis.

Interactions of atmospheric neutrinos with quantum-gravity-induced fluctuations of the metric of spacetime would lead to decoherence. The IceCube Collaboration constrains such interactions with atmospheric neutrinos.

Interlocked molecules commonly include one (or more) monocyclic component — examples comprising bicyclic or tricyclic structures are much more rare and usually involve metal–ligand coordination or additional templates. Now, the dynamic self-assembly of twenty organic molecules in a one-pot synthesis has been shown to produce tetrahedral covalent cages, which interpenetrate during the process to form triply interlocked dimers.

A particle shower detected by the IceCube Neutrino Observatory at the very high energy of the Glashow resonance demonstrates its potential for the study of high-energy particle physics and astrophysics.

A crystalline porous organic cage molecule is shown to have exceptional specificity for separating different structural isomers of C9 aromatics. Uniquely, this solid-state specificity is preconfigured in the discrete molecular building block, which shows an analogous specificity in solution. Both solution and solid-state behaviours can be understood by molecular dynamics simulations.

Drawing from real-life scenarios and insights shared at the RAISE (Responsible AI for Social and Ethical Healthcare) conference, we highlight the critical need for AI in health care (AIH) to primarily benefit patients and address current shortcomings in health care systems such as medical errors and access disparities.

The genetic basis of metabolic diseases is incompletely understood. Here, by high-throughput phenotyping of 2,016 knockout mouse strains, Rozman and colleagues identify candidate metabolic genes, many of which are associated with unexplored regulatory gene networks and metabolic traits in human GWAS.

The astronomical event GW170817, detected in gravitational and electromagnetic waves, is used to determine the expansion rate of the Universe, which is consistent with and independent of existing measurements.

A new metal–organic framework has several conformational degrees of freedom that can be modified by the external chemical environment to change the structure and trigger the uptake of a guest molecule.

The International Mouse Phenotyping Consortium reports the generation of new mouse mutant strains for more than 5,000 genes, including 2,850 novel null, 2,987 novel conditional-ready and 4,433 novel reporter alleles.

Laser-driven X-rays can provide ultrashort pulses of broadband light, well suited for femtosecond timescale absorption spectroscopy. Here the authors measure the extended X-ray absorption features of a copper sample using a laser wakefield accelerator, in a single shot; important for studying samples driven to extreme and non-equilibrium states.

The IceCube Collaboration reports a search for quantum gravity effects imprinted in flavour conversions of astrophysical neutrinos. No evidence for anomalous conversions between neutrino flavours is observed.