Search

By integrating the serum concentration of a broadly neutralizing antibody (bNAb) with its in vitro 80% inhibitory concentration, the PT₈₀ biomarker may be used to guide target levels of bNAbs for effective prevention of HIV-1 acquisition.

Peter Robinson and colleagues performed exome sequencing on three siblings to identify mutations in PIGV in Hyperphosphatasia-Mental Retardation (HPMR) syndrome.

Clathrin helps cells internalize and transport cargo by interacting with membrane adaptor proteins. Here, the authors reveal that adaptor proteins bind selectively, hierarchically and simultaneously to three sites of clathrin’s N-terminal domain.

In Alzheimer’s disease (AD) tau and neurodegeneration have complex regional relationships. Here, the authors show neuronal hypometabolism discordant with tau burden defines functional resilience or susceptibility to Alzheimer’s pathology via limbic/cortical axes. Susceptible groups have faster cognitive decline and evidence of non-Alzheimer’s pathologies.

mTORC1 regulates cellular growth from the lysosome, but how changes in the organisation of the lysosomal system affect mTORC1 signalling is poorly understood. Here the authors show that amino acid-dependent Rap1-mediated changes in lysosomal abundance determine overall signalling output of mTORC1.

Acute Myeloid Leukemia (AML) develops following multiple mutations of differing impact. Here, the authors show that activating mutations of CSF3R co-operate with loss-of-function mutations of CEBPA to promote AML development through an enhancer-dependent mechanism.

Prime editing uses Cas9 nickase fused to a reverse transcriptase to edit genetic information. Here, the authors prime edit primary adult stem cells in 3D organoid cultures to show functional correction of pathogenic mutations without genome-wide off-target effects.

The transcriptional regulator PRDM15 is expressed at low levels in normal tissues but overexpressed in B-cell lymphomas. Here, the authors show that PRDM15 depletion does not affect adult somatic cell homeostasis but leads to a metabolic crisis which impairs B-cell lymphomagenesis.

MXenes with borate polyanion terminations are synthesized using a flux-assisted eutectic molten etching approach. These triatomic-layer terminations empower MXenes with considerably improved charge transport and charge storage capabilities.

Application of correlative light and electron microscopy (CLEM) in plants remains challenging. Here, the authors use Click-iT chemistry as a tool for CLEM, due to its unique properties in resin permeability and super-resolution microscopy. They use this approach to study cellular physiology in Arabidopsis.

The differential effects of TP53 missense mutations in colorectal cancer (CRC) remain to be explored. Here the authors compare the gain of function impact of two frequent TP53 mutations in CRC and show that p53R273 mutants control a transcriptional program, which drives oncogenic signaling pathways, leading to a more aggressive phenotype and worse patient outcome.

Genome-wide ancient DNA data from individuals from the Middle Bronze Age to Iron Age documents large-scale movement of people from the European continent between 1300 and 800 bc that was probably responsible for spreading early Celtic languages to Britain.

The authors use chronic in vivo imaging to study pyramidal neurons before and after deletion of the tumor suppressor gene Pten in mature neurons of the mouse cortex. They find that Pten/mTOR signaling only regulates growth of layer 2/3 apical dendrites.

Phytochromes are photoreceptors that are present in plants, bacteria and fungi. Here the authors present crystal structures of the phytochrome Agp2 from Agrobacterium fabrum in the parent Pfr state as well as a functional Meta-F intermediate and discuss mechanistic implications for photoconversion.

In this study the authors identify a possible link between the gene FAM222A and brain atrophy. The protein it encodes is found to accumulate in plaques seen in Alzheimer’s disease, and functional analysis suggests it interacts with amyloid-beta.

Established antigen-specific T-cell responses can be suppressed by conjugating the antigen to a glycosylated polymer, as shown in a mouse model of multiple sclerosis and with the suppression of responses to vaccination in non-human primates.

Antibody Mediated Prevention (AMP) trials showed that the broadly neutralizing antibody VRC01 could prevent some HIV-1 acquisitions. Here the authors use VRC01 levels and the sensitivity of each acquired HIV virus to predict viral loads in the AMP studies and show that VRC01 influenced viral loads, though potency was lower in vivo than expected.

Developing reliable resource characterization while guaranteeing resource efficiency is essential in practical quantum information processing. In this work, the authors show that the data obtained from entanglement distillation protocols can be further processed to efficiently and robustly characterize the entangled resources.

In a phase 2 trial, the oral type II RAF inhibitor tovorafenib exhibited an overall response rate of 67% in patients with BRAF-altered relapsed/refractory pediatric low-grade glioma.

Multi-ancestry genome-wide association meta-analysis identifies new risk loci for CAC. Functional evidence implicates candidate causal genes as regulators of smooth muscle cell-mediated calcification.

Quantum computing is a promising technology to solve complex challenges that would take classical computers an impractical amount of time. This Perspective discusses the current state of quantum computing and possible applications in enzyme engineering and biocatalysis.

The interplay between amyloid and tau pathology in Alzheimer’s disease is still not well understood. Here, the authors show that amyloid-related increased in soluble p-tau is related to subsequent accumulation of tau aggregates and cognitive decline in early stage of the disease.

An observational study of adolescent females’ Internet use reveals how online behaviours coupled with offline psychosocial and contextual factors are associated with subsequent vulnerability to Internet-initiated victimization.

Membrane contact sites between organelles have been shown to play important biological roles. Here, the authors show that at the ER, PDZD8 associates with Protrudin and also with Rab7 endosomes and recruits mitochondria to form three-way contacts.

Central Anatolia harbored some of the earliest farming societies outside the Fertile Crescent of the Near East. Here, the authors report and analyze genome-wide data from a 15,000-year-old Anatolian hunter-gatherer and from seven Anatolian and Levantine early farmers, and suggest high genetic continuity between the hunter-gatherers and early farmers of Anatolia.

Infant gliomas behave differently to their childhood or adult counterparts. Here, the authors perform a large-scale genetic analysis of these tumours, revealing genetic alterations which may offer therapeutic opportunities.

During clathrin-mediated endocytosis in yeast, endocytic coat adaptors, Sla2 and Ent1, must remain attached to the plasma membrane to transmit force from the actin cytoskeleton required for membrane invagination. Here authors present a cryo-EM structure of a 16-mer complex of the ANTH and ENTH membrane-binding domains from Sla2 and Ent1 bound to PIP₂ that constitutes the anchor to the plasma membrane.

The use of clean energy sources is essential for the humankind. Here, authors show new experiments carried out with Deuterium-Tritium fusion reactions. Results show that energy production by such reactions can be more efficient than expected, confirming fusion as an alternative to fossil fuels.

Progressive diseases tend to be heterogeneous in their underlying aetiology mechanism, disease manifestation, and disease time course. Here, Young and colleagues devise a computational method to account for both phenotypic heterogeneity and temporal heterogeneity, and demonstrate it using two neurodegenerative disease cohorts.

Vaccination with multiple doses has been proven effective against severe COVID-19, but protection levels widely vary among individuals. This study examines the serological and immunological profiles in recipients of multiple doses of Pfizer BNT162b2 vaccine for immune markers that correlate with protection against and susceptibility for SARS-CoV-2 infection.

The depth of oxygen penetration and microbial activity in marine sediments varies by region. Sediment cores from the South Pacific Gyre host oxygen and aerobic microbial communities to at least 75 metres below the sea floor.

Antibodies against Plasmodium falciparum glutamic-acid-rich protein (PfGARP), an antigen expressed on the surface of infected red blood cells, kill P. falciparum parasites by inducing programmed cell death and reduce the risk of severe malaria.

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.

Alzheimer’s disease is heterogeneous in its neuroimaging and clinical phenotypes. Here the authors present a semi-supervised deep learning method, Smile-GAN, to show four neurodegenerative patterns and two progression pathways providing prognostic and clinical information.

Single-cell analyses reveal cDC1 as conserved immunological drivers of non-alcoholic steatohepatitis in mice and humans

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

Systematic characterization of longitudinal tau variability in human Alzheimer’s disease using an unbiased subtyping algorithm reveals four trajectories of tau deposition with distinct clinical features.

The KL-VS haplotype of the Klotho gene has been associated with reduced risk of Alzheimer’s disease and dementia. Here the authors show an association between the KL-VS haplotype and amyloid-dependent tau accumulation using PET data.

The accretion geometry of X-ray binary Cygnus X-3 is determined here from IXPE observations. X-ray polarization reveals a narrow funnel with reflecting walls, which focuses emission, making Cyg X-3 appear as an ultraluminous X-ray source.

Ian Tomlinson and colleagues report the identification of germline variants in POLE and POLD1 that are susceptibility alleles for colorectal cancer. POLE and POLD1 encode DNA polymerases that function in DNA replication.

Mutations in BRAT1 are associated with neurodevelopmental delay and neurodegeneration. Here, the authors show that BRAT1 is a component of Integrator and is important for processing of specific RNAs. They further demonstrate that BRAT1 mutant patient-derived cells exhibit reduced levels of the Integrator catalytic subunit and increased levels of misprocessed UsnRNAs and impaired RNA processing.

Measurements and simulations of several high-mobility conjugated polymers show that their charge transport properties reflect an almost complete lack of disorder in the polymers, despite their amorphous microstructures, resulting from the resilience of the planar polymer backbone conformations to side-chain disorder.

The BIN1 SNP rs744373 is associated with higher CSF tau and phosphorylated tau levels. Here the authors show, using PET imaging, that this SNP is associated with tau accumulation in the brain as well as impaired memory in older individuals without dementia.

Here, the authors characterize immunological and microbiome alterations in a cohort of obese asthmatics, finding that disease severity negatively correlates with fecal abundance of Akkermansia muciniphila, and show in a mouse model that administration of A. muciniphila reduces airway hyper-reactivity and airway inflammation.

Transient glucose restriction after the activation of CD8⁺ T_E cells ex vivo induces metabolic remodelling that enhances effector functions and tumour clearance in mice.

With conventional scanning transmission electron microscopy, some sensitive materials are difficult to image with atomic resolution. The authors present a method of mixed-state electron ptychography that enables picometer precision with fast acquisition and low dosage.