Search

A modeling approach to assess the global risk of Plasmodium falciparum histidine-rich protein 2 and 3 gene deletions identifies ten priority African countries for surveillance and could inform malaria control policies.

Individuals with schizophrenia show reduced structural similarity in temporal, cingulate, and insular lobes, especially those with worse cognition and symptoms, affecting late maturing association areas with low metabolism and high neurotransmission.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Zhao et al. used single-cell and spatial multiomics data analysis of human and mouse lung adenocarcinoma tumors and cell lines to reveal TP53 mutation-associated changes in cancer cells and their microenvironment.

Here, the authors identify the microbiota-derived corisin as a driver of diabetic kidney fibrosis via cellular aging and show that targeting corisin with a monoclonal antibody alleviates disease in mice, suggesting a potential therapeutic avenue.

During sea urchin development, the micromeres form via asymmetric cell division and act as organizers to induce gastrulation. Here they show that micromeres have unique metabolic characteristics and that disrupting their metabolic activity blocks gastrulation induction.

Expanding the complexity of genetically encoded peptides is a long-standing challenge at the intersection of chemistry and biology. Now it has been shown that linear peptides with a reactive N-terminal β- or γ-keto amide can be synthesized ribosomally and elaborated to generate atropisomeric and/or macrocyclic peptides with embedded pharmacophores.

Flores et al. show that brain-penetrant eIF2B agonists suppress ISR activation in cellular and mouse models of ALS and reduce ISR biomarkers in humans, enabling further clinical studies of ISR inhibition in individuals with neurological diseases

Transposable elements are genetic parasites that have colonised genomes and they express as parts of coding and noncoding RNAs. Here, the authors explore how they are expressed in transcripts in normal human development, and how they alter transcript dynamics.

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.

TCR-T cells are T cells engineered to express a specific T cell receptor. Here the authors present a TCR-T cell that targets CTNNB1-S37F, corresponding to a shared cancer driver mutation. This immunotherapy killed solid tumors when applied to a patient-derived xenograft model in mice.

Preventing endosomal damage sensing or using lipids that create reparable endosomal holes reduces inflammation caused by RNA–lipid nanoparticles while enabling high RNA expression.

Kohio et al. map HIV-1 integration sites across multiple tissues from early infections. The results identify brain-specific patterns and tissue-dependent preferences that may influence HIV persistence and disease risk.

Caloric restriction improves Alzheimer’s Disease outcomes in mice, but this diet not only reduces calories, but imposes a prolonged fast between meals. Here, the authors show this fast is essential to improve Alzheimer’s pathology and cognition.

Decreased brain coenzyme Q₁₀ levels cause encephalopathy and are associated with neurodegeneration; supplementation with 4-HMA or 4-HB restores coenzyme Q₁₀ synthesis in mice and humans with HPDL variants, improving survival and neurological symptoms in HPDL-driven mitochondrial encephalopathy.

The reconstruction of phospholipase Ce in complex with a Fab identifies two of its N-terminal regulatory domains and helps define the basal state of the enzyme.

This study shows how Escherichia coli ApaH hydrolyzes enigmatic Np₄N alarmones and decaps Np₄-capped RNAs, thereby impacting their lifetimes. Key features enable ApaH to bind RNA substrates in two orientations, depending on the cap and the first RNA nucleotide.

Here the authors analyze de novo mutations in >10,000 parent-offspring trios and find that ancestry and smoking independently associate with mutation rate, but that common genetic variants likely contribute little to mutation rate variation.

Systematic analysis from the Global Burden of Disease study reported that, despite global improvements from 1990 to 2021, dietary iron deficiency-associated disease burden remains high in women, children and residents in low socio-demographic index countries.

A remora-inspired mechanical underwater adhesive device adheres securely to a range of soft substrates and maintains performance under extreme pH and moisture conditions, with potential applications in biosensing and drug delivery.

Exome sequencing of 851 trios from more than 2,500 individuals finds 187 genes with de novo mutations that contribute to meningomyelocele (spina bifida) and highlights critical pathways required for neural tube closure.

Here they show that HDAC6 inhibition regulates fumarate hydratase (FH), disrupts mitochondria, increases fumarate, and causes cancer cell death. This suggests that HDAC6 inhibition could be a strategy to target tumour metabolism indirectly.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

Molecules that recapitulate the structure and prion-like activity of misfolded tau hold promise as more relevant models of pathological tau propagation. Now, the macrocyclization of short tau fragments affords proteomimetics that seed tau aggregation in cells and adopt a β-arch conformation resembling those found in filaments from patient-derived extracts.

Chang, Cao et al. examine local trends associated with the diagnosis and treatment of de novo metastatic breast cancer. Findings show that black race, hypertension, diabetes, as well as the presence of visceral metastases are associated with a worse prognosis.

This study shows that brain connectivity changes in Huntington’s disease begin decades before symptoms, shifting from hyper- to hypoconnectivity, with links to specific neurotransmitter systems specially in granular and infragranular cortical layers.

SARS-COV-2 wastewater surveillance may enable early identification of emerging variants. Here, authors compare variants detected in wastewater from Stockholm city, its airport, aircraft, the wider airport region, wastewater plants, and hospitals.

PAPD5 is responsible for adenylation of microRNAs. Here, the authors show that elevated level of PAPD5 enhances the adenylation and reduced expression of miR-7-5p. As a result, expression of TAB2, a target of miR-7-5p, is induced triggering neuronal apoptosis in Huntington’s disease.

Superlattices, with a length scale and structure that differs from the parent lattice of the host material, are well-known to allow for remarkable new electronic and magnetic properties. Here, Xie et al. synthesize Cr_1/4TaS₂, and find that it exhibits an unusual anomalous Hall effect below the Néel temperature even in stoichiometric high-quality crystals.

The RhoA GTPase binds to the EF hands of phospholipase Ce to regulate its function through a mechanism involving allostery and interfacial activation.

Merkel cell carcinoma (MCC) is a rare aggressive skin cancer with limited therapeutic options. In this work, the authors identify aurora kinase B (AURKB) as a critical therapeutic target for MCC, supported by tumour shrinkage and increased survival when using the AURKB inhibitor AZD2811 nanoparticle formulation in MCC preclinical models.