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Genetic variants produce complex phenotypic effects that confound current assays and predictive models. We developed variant in situ sequencing (VIS-seq), a pooled, image-based method measuring variant effects on molecular and cellular phenotypes in diverse cell types. Applying VIS-seq to ∼3,000 LMNA and PTEN variants yielded high-dimensional morphological profiles capturing changes in protein abundance, localization, activity, and cell architecture. VIS-seq identified a subset of...

Spontaneous fluctuations in attention can impede adaptation to changing goals and environments. Endogenous control over attentional shifts, referred to as attentional flexibility, is prone to disruption in children with attention deficit disorders. Here we studied in vivo intracranial recordings in children with epilepsy to identify a reproducible neural signature of attentional control that could predict and prevent impending lapses in real time. Machine learning classifiers were trained on...

There are around 100 genes or copy-number variations used in genetic testing for autism spectrum disorder (ASD)^(1,2). The established genes are protein coding, and the associated phenotypes usually extend beyond sociobehavioural traits seen in autism, including cognitive/medical complexities and attention deficit hyperactivity disorder (ADHD)^(3,4). We examined whole-genome sequencing data in cases of ASD (9,349) and controls (8,332) and identify 27 male individuals with ASD with X-chromosome...

Reactive oxygen species (ROS) burst and subsequent recruitment to the ischemic brain characterize neutrophil activation in the hyperacute phase of ischemic stroke, yet the underlying metabolic drivers remain elusive. Here, we report that neutrophil-intrinsic chemokine-like factor 1 (CKLF1) acts as a key immunometabolic regulator following stroke. CKLF1 was rapidly upregulated in neutrophils within 6 h post-ischemia in both humans and mice. Mechanistically, CKLF1 bound directly to the tetrameric...

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In recent years, a deluge of big and diverse datasets from hundreds of plant species coupled with spectacular innovations in artificial intelligence (AI) and generative AI (GenAI), has altered the landscape of plant science. These developments are increasingly democratizing the field, reducing the entry barriers to complex data analysis and enabling a new wave of innovative research while introducing new challenges. Therefore, in this era, it is critical that we train the next generation of...

CONCLUSION: ATRIP plays a critical role in DNA damage response and genomic stability. Our findings support its candidacy as a novel ovarian cancer susceptibility gene.

The increasing global prevalence of droughts due to climate change poses a major threat to food security, necessitating the development of drought-tolerant crops. To respond appropriately to environmental perturbations, plants undergo widespread transcriptional reprogramming at both the gene expression and splicing levels. Differential splicing dynamically alters the ratio of splice isoforms, generating transcriptomic diversity that can be translated into novel protein isoforms or fine-tune gene...

CONCLUSIONS: Modern radiotherapy techniques allow safe delivery of high radiation doses for LAPC. SBRT provides excellent and durable local control with low rates of treatment-related grades ≥3 toxicities.

CONCLUSIONS: The coupled platform we have developed has enabled direct volumetric imaging of the dynamics of pathogen binding and concomitant recruitment of membrane receptors on live cells. The platform closes a critical gap between optically sectioned fluorescence and label-free 3D phase imaging and can be adapted to other receptor-ligand systems that would benefit from correlated structural and functional insights.

MOTIVATION: Segmentation and automated genome annotation (SAGA) techniques, such as Segway and ChromHMM, assign labels to every part of the genome, identifying similar patterns across multiple genomic input signals. Inferring biological meaning in these patterns remains challenging. Doing so requires a time-consuming process of manually downloading reference data, running multiple analysis methods, and interpreting many individual results.

Long-term hematopoietic stem cells (LT-HSC) maintain lifelong hematopoiesis while preserving the stem cell compartment through self-renewal. The human LT-HSC compartment is molecularly and functionally heterogeneous and also varies across ontogeny. Dissecting the molecular basis for this variation is impeded by the paucity of immunophenotypic markers to resolve LT-HSC heterogeneity. Here, we identified ATPase plasma membrane calcium transporting 1 (ATP2B1/PMCA1) as a cell surface marker that is...

Despite most acute myeloid leukemia (AML) patients achieving complete remission after induction chemotherapy, two-thirds relapse within 5 years. AML follows a cellular hierarchy sustained by leukemia stem cells (LSCs), which drive tumor progression and relapse. Little is known about the genetic determinants driving LSCs stemness properties. By identifying chromatin variants from accessibility measurements across LSCs, hematopoietic stem cells and downstream progeny, we identified transposable...

CONCLUSIONS: Our procedure leads to successful (re)use of data in FL-based consortia without the need to impose a common schema at every point of origin of data.

Exposure to feelings of another can shape how we feel and think in that context. We propose that exposure to the feelings of multiple others carries broader implications that extend beyond the exposure context. We argue that people identify patterns of affective reactions in the social group, which leads them to infer affect norms. These norms, in turn, serve as benchmarks for subsequent social judgments. In four studies (N = 418), three of which were preregistered, we exposed participants to...

Inflammatory injury to the intestine triggers a reprogramming of the intestinal epithelium to a fetal-like state that drives rapid restoration of the epithelial barrier. Although the intestinal microbiota is a key modulator of inflammation, its role in influencing epithelial fetal-like stem cell reprogramming and consequent restitution remains unclear. Using irradiation (IR) injury as a model for small intestinal epithelium injury and repair, we found that the intestinal microbiota accelerated...

Mutations in the X-linked MECP2 gene cause the progressive neurodevelopmental disorder Rett syndrome. Pathogenic missense mutation hotspots exist in the protein's Methyl DNA binding Domain (MBD), and the Nuclear receptor Co-Repressor (NCoR) Interaction Domain (NID), indicating these regions as critical for MeCP2 function. The NID binds to a co-repressor complex allowing transcriptional repression at target genes. A putative RNA Binding Domain (RBD) was identified that overlaps with the NID, yet...

Deciphering how genes interact within human cells is essential for understanding their functional wiring and for developing targeted therapeutic strategies. In this study, we present a genome-scale map of genetic interactions in the human haploid cell line HAP1, based on CRISPR-based perturbation of ∼4 million gene pairs. The resulting network comprises ∼89,000 high-confidence gene-gene interactions, organizing genes into hierarchical modules corresponding to protein complexes and pathways,...

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CONCLUSIONS: Our findings show that aggregate wearable data often fail to generalize across populations, oversimplifying pregnancy-related physiological and subjective changes. This simplification can obscure individual trajectories, leading to generalized insights that may not reflect many pregnant women's experiences. Our results highlight the impact of heterogeneity on pregnancy outcomes, emphasizing the need to move beyond one-size-fits-all models and leverage DHT for personalized care.