Global meta-analysis shows action is needed to halt genetic diversity loss.

Mitigating loss of genetic diversity is a major global biodiversity challenge. To meet recent international commitments to maintain genetic diversity within species, we need to understand relationships between threats, conservation management and genetic diversity change. Here we conduct a global analysis of genetic diversity change via meta-analysis of all available temporal measures of genetic diversity from more than three decades of research.

Degradable thermosets via orthogonal polymerizations of a single monomer.

Crosslinked thermosets are highly durable materials, but overcoming their petrochemical origins and inability to be recycled poses a grand challenge. Many strategies to access crosslinked polymers that are bioderived or degradable-by-design have been proposed, but they require several resource-intensive synthesis and purification steps and are not yet feasible alternatives to conventional consumer materials. Here we present a modular, one-pot synthesis of degradable thermosets from the commercially available, biosourced monomer 2,3-dihydrofuran (DHF).

Warming and cooling catalyse widespread temporal turnover in biodiversity.

Turnover in species composition through time is a dominant form of biodiversity change, which has profound effects on the functioning of ecological communities. Turnover rates differ markedly among communities, but the drivers of this variation across taxa and realms remain unknown. Here we analyse 42,225 time series of species composition from marine, terrestrial and freshwater assemblages, and show that temporal rates of turnover were consistently faster in locations that experienced faster temperature change, including both warming and cooling.

Bat genomes illuminate adaptations to viral tolerance and disease resistance.

Zoonoses are infectious diseases transmitted from animals to humans. Bats have been suggested to harbour more zoonotic viruses than any other mammalian order. Infections in bats are largely asymptomatic, indicating limited tissue-damaging inflammation and immunopathology.

Variable stressor exposure shapes fitness within and across generations.

Environmental variation has long been considered a key driver of evolutionary change, predicted to shape different strategies, such as genetic specialization, plasticity, or bet-hedging to maintain fitness. However, little evidence is available with regards to how the periodicity of stressors may impact fitness across generations. To address this gap, I conducted a reciprocal split-brood experiment using the freshwater crustacean, Daphnia magna, and an ecologically relevant environmental stressor, ultraviolet radiation (UVR).

Non-additive dosage-dependent effects of TaGS3 gene editing on grain size and weight in wheat.

Loss-of-function mutations induced by CRISPR-Cas9 in the TaGS3 gene homoeologs show non-additive dosage-dependent effects on grain size and weight and have potential utility for increasing grain yield in wheat. The grain size in cereals is one of the component traits contributing to yield. Previous studies showed that loss-of-function (LOF) mutations in GS3, encoding Gγ subunit of the multimeric G protein complex, increase grain size and weight in rice.

APOE4 and sedentary lifestyle synergistically impair neurovascular function in the visual cortex of awake mice.

Reduced cerebral blood flow occurs early in the development of Alzheimer's disease (AD), but the factors producing this reduction are unknown. Here, we ask whether genetic and lifestyle risk factors for AD-the ε4 allele of the Apolipoprotein (APOE) gene, and physical activity-can together produce this reduction in cerebral blood flow which leads eventually to AD. Using in vivo two-photon microscopy and haemodynamic measures, we record neurovascular function from the visual cortex of physically active or sedentary mice expressing APOE3 and APOE4 in place of murine APOE.

A manifesto for a globally diverse, equitable, and inclusive open science.

The field of psychology has rapidly transformed its open science practices in recent years. Yet there has been limited progress in integrating principles of diversity, equity and inclusion. In this Perspective, we raise the spectre of Questionable Generalisability Practices and the issue of MASKing (Making Assumptions based on Skewed Knowledge), calling for more responsible practices in generalising study findings and co-authorship to promote global equity in knowledge production.

Synchronized long-read genome, methylome, epigenome and transcriptome profiling resolve a Mendelian condition.

Resolving the molecular basis of a Mendelian condition remains challenging owing to the diverse mechanisms by which genetic variants cause disease. To address this, we developed a synchronized long-read genome, methylome, epigenome and transcriptome sequencing approach, which enables accurate single-nucleotide, insertion-deletion and structural variant calling and diploid de novo genome assembly. This permits the simultaneous elucidation of haplotype-resolved CpG methylation, chromatin accessibility and full-length transcript information in a single long-read sequencing run.

Fabrication of heteroatom-doped graphene-porous organic polymer hybrid materials via femtosecond laser writing and their application in VOCs sensing.

Graphene, a two-dimensional material featuring densely packed sp-hybridized carbon atoms arranged in a honeycomb lattice, has revolutionized material science. Laser-induced graphene (LIG) represents a breakthrough method for producing graphene from both commercial and natural precursors via direct laser writing, offering advantages such as simplicity, efficiency, and cost-effectiveness. This study demonstrates a novel approach to synthesize a composite material exclusively from a porous organic polymer (POP) by direct femtosecond laser writing on a compressed imide-linked porous organic polymer substrate.

Genetic ancestry concordant RNA splicing in prostate cancer involves oncogenic genes and associates with recurrence.

Black men suffer disproportionately from prostate cancer (PCa) compared to men of other races and ethnicities. Comparing the molecular landscape of PCa among Black and White patients has the potential to identify targets for development of new precision medicine interventions. Herein, we conducted transcriptomic analysis of prostate tumors and paired tumor-adjacent normals from self-reported Black and White PCa patients and estimated patient genetic ancestry.

Spatially resolved transcriptomics and graph-based deep learning improve accuracy of routine CNS tumor diagnostics.

The diagnostic landscape of brain tumors integrates comprehensive molecular markers alongside traditional histopathological evaluation. DNA methylation and next-generation sequencing (NGS) have become a cornerstone in central nervous system (CNS) tumor classification. A limiting requirement for NGS and methylation profiling is sufficient DNA quality and quantity, which restrict its feasibility.

Genetic associations between orexin genes and phenotypes related to behavioral regulation in humans, including substance use.

The hypothalamic neuropeptide system of orexin (hypocretin) neurons provides projections throughout the neuraxis and has been linked to sleep regulation, feeding and motivation for salient rewards including drugs of abuse. However, relatively little has been done to examine genes associated with orexin signaling and specific behavioral phenotypes in humans. Here, we tested for association of twenty-seven genes involved in orexin signaling with behavioral phenotypes in humans.

Neural signatures of risk-taking adaptions across health, bipolar disorder, and lithium treatment.

Cognitive and neural mechanisms underlying bipolar disorder (BD) and its treatment are still poorly understood. Here we examined the role of adaptations in risk-taking using a reward-guided decision-making task. We recruited volunteers with high (n = 40) scores on the Mood Disorder Questionnaire, MDQ, suspected of high risk for bipolar disorder and those with low-risk scores (n = 37).

Understanding and promoting equitable post-discharge care in firearm injury survivors: a retrospective chart review.

Patients that survive firearm injuries frequently require follow-up care. This study aims to explore demographic characteristics of patients presenting to the emergency department for post-firearm injury care and to understand the reasons for their return visits. This was a retrospective chart review of all emergency department and readmission patient encounters for post-firearm injury care during the study period, January 1, 2019 to December 31, 2022, at an urban safety net hospital.

Fluo-Cast-Bright: a deep learning pipeline for the non-invasive prediction of chromatin structure and developmental potential in live oocytes.

In mammalian oocytes, large-scale chromatin organization regulates transcription, nuclear architecture, and maintenance of chromosome stability in preparation for meiosis onset. Pre-ovulatory oocytes with distinct chromatin configurations exhibit profound differences in metabolic and transcriptional profiles that ultimately determine meiotic competence and developmental potential. Here, we developed a deep learning pipeline for the non-invasive prediction of chromatin structure and developmental potential in live mouse oocytes.

Engineering synthetic signaling receptors to enable erythropoietin-free erythropoiesis.

Blood transfusion plays a vital role in modern medicine, but frequent shortages occur. Ex vivo manufacturing of red blood cells (RBCs) from universal donor cells offers a potential solution, yet the high cost of recombinant cytokines remains a barrier. Erythropoietin (EPO) signaling is crucial for RBC development, and EPO is among the most expensive media components.

scRNA seq of an F1 cross of Marek's disease resistant and susceptible chickens identifies allele specific expression signatures enriched in transcription modulators.

Marek's disease (MD), a T cell lymphoma disease in chickens, is caused by the Marek's disease virus (MDV) found ubiquitously in the poultry industry. Genetically resistant Line 6 (L6) and susceptible Line 7 (L7) chickens have been instrumental to research on avian immune system response to MDV infection. In this study we characterized molecular signatures unique to splenic immune cell types across different genetic backgrounds 6 days after infection.

Three-dimensional diffractive acoustic tomography.

Acoustically probing biological tissues with light or sound, photoacoustic and ultrasound imaging can provide anatomical, functional, and/or molecular information at depths far beyond the optical diffusion limit. However, most photoacoustic and ultrasound imaging systems rely on linear-array transducers with elevational focusing and are limited to two-dimensional imaging with anisotropic resolutions. Here, we present three-dimensional diffractive acoustic tomography (3D-DAT), which uses an off-the-shelf linear-array transducer with single-slit acoustic diffraction.

Assessment of Hsp90β-selective inhibitor safety and on-target effects.

The heat shock protein 90 (Hsp90) family of molecular chaperones mediates the folding and activation of ~ 400 client proteins, many of which contribute to oncogenesis. As a result, Hsp90 pan-inhibitors, which inhibit all four Hsp90 isoforms, have been investigated in the clinic for the treatment of cancer. Unfortunately, detrimental side effects were observed and hindered the clinical development of pan-Hsp90 inhibitors.

Salicylic acid confers cadmium tolerance in wheat by regulating photosynthesis, yield and ionic homeostasis.

Wheat (Triticum aestivum L.) productivity and quality can be threatened by soil cadmium (Cd) contamination, posing a concern to food security. Salicylic acid (SA) is an endogenously produced signaling molecule that activates the defense system imparting abiotic stress tolerance in plants.

Molecular and pharmacological heterogeneity of ETV6::RUNX1 acute lymphoblastic leukemia.

ETV6::RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukemia (ALL) associated with favorable prognosis, but the optimal therapy for this subtype remains unclear. Profiling the genomic and pharmacological landscape of 194 pediatric ETV6::RUNX1 ALL cases, we uncover two transcriptomic clusters, C1 (61%) and C2 (39%). Compared to C1, the C2 subtype features higher white blood cell counts and younger age at diagnosis, as well as better early treatment responses.

Is there a mental health diagnostic crisis in primary care? Current research practices in global mental health cannot answer that question.

In low- and middle-income countries, fewer than 1 in 10 people with mental health conditions are estimated to be accurately diagnosed in primary care. This is despite more than 90 countries providing mental health training for primary healthcare workers in the past two decades. The lack of accurate diagnoses is a major bottleneck to reducing the global mental health treatment gap.

Single cell profiling of circulating autoreactive CD4 T cells from patients with autoimmune liver diseases suggests tissue imprinting.

Autoimmune liver diseases (AILD) involve dysregulated CD4 T cell responses against liver self-antigens, but how these autoreactive T cells relate to liver tissue pathology remains unclear. Here we perform single-cell transcriptomic and T cell receptor analyses of circulating, self-antigen-specific CD4 T cells from patients with AILD and identify a subset of liver-autoreactive CD4 T cells with a distinct B-helper transcriptional profile characterized by PD-1, TIGIT and HLA-DR expression. These cells share clonal relationships with expanded intrahepatic T cells and exhibit transcriptional signatures overlapping with tissue-resident T cells in chronically inflamed environments.

Time-resolved Brownian tomography of single nanocrystals in liquid during oxidative etching.

Colloidal nanocrystals inherently undergo structural changes during chemical reactions. The robust structure-property relationships, originating from their nanoscale dimensions, underscore the significance of comprehending the dynamic structural behavior of nanocrystals in reactive chemical media. Moreover, the complexity and heterogeneity inherent in their atomic structures require tracking of structural transitions in individual nanocrystals at three-dimensional (3D) atomic resolution.