Aggregator

The eukaryotic cell division cycle is a highly conserved process, featuring fluctuations in protein localization and abundance required for key cell cycle transitions. Here, we present a protocol for the spatiotemporal analysis of the proteome during the budding yeast cell division cycle using live-cell imaging. We describe steps for strain construction, cell cultivation, microscopy, and image analysis. Variations of this protocol can be applied for the spatiotemporal analysis of the proteome in...

Medulloblastoma (MB), a heterogeneous pediatric brain tumor, poses challenges in the treatment of tumor recurrence and dissemination. To characterize cellular diversity and genetic features, we comprehensively analyzed single-cell/nucleus RNA sequencing (sc/snRNA-seq), single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq), and spatial transcriptomics profiles and identified distinct cellular populations in SHH (sonic hedgehog) and Group_3 subgroups, with varying...

No abstract

CONCLUSION: Together, these results provide further insight into the microbial factors that may be driving disease severity. Video Abstract.

Lupins are promising protein crops that accumulate toxic quinolizidine alkaloids (QAs) in the seeds, complicating their end-use. QAs are synthesized in green organs (leaves, stems, and pods) and a subset of them is transported to the seeds during fruit development. The exact sites of biosynthesis and accumulation remain unknown; however, mesophyll cells have been proposed as sources, and epidermal cells as sinks. We investigated the exact sites of QA biosynthesis and accumulation in biosynthetic...

Maturation of αβ lineage T cells in the thymus relies on the formation and cell surface expression of a pre-T cell receptor (TCR) complex, composed of TCRβ chain and pre-TCRα (pTCRα) chain heterodimers, giving rise to a diverse T cell repertoire. Genetic aberrations in key molecules involved in T cell development lead to profound T cell immunodeficiency. Definitive genetic diagnosis guides treatment choices and counseling. In this study, we describe the role of whole genome sequencing (WGS) in...

In neurons, the acquisition of a polarized morphology is achieved upon the outgrowth of a single axon from one of several neurites. Small extracellular vesicles (sEVs), such as exosomes, from diverse sources are known to promote neurite outgrowth and thus may have therapeutic potential. However, the effect of fibroblast-derived exosomes on axon elongation in neurons of the central nervous system under growth-permissive conditions remains unclear. Here, we show that fibroblast-derived sEVs...

Continuously emerging SARS-CoV-2 Omicron subvariants pose a threat thwarting the effectiveness of approved COVID-19 vaccines. Especially, the protection breadth and degree of these vaccines against antigenically distant Omicron subvariants is unclear. Here, we report the immunogenicity and efficacy of a bivalent mRNA vaccine, PTX-COVID19-M1.2 (M1.2), which encodes native spike proteins from Wuhan-Hu-1 (D614G) and Omicron BA.2.12.1, in mouse and hamster models. Both primary series and booster...

Epithelial cells can become polyploid upon tissue injury, but mechanosensitive cues that trigger this state are poorly understood. Using an Madin Darby Canine Kidney (MDCK) cell knock-out/reconstitution system, we show that α-catenin mutants that alter force-sensitive binding to F-actin or middle (M)-domain promote cytokinesis failure and binucleation, particularly near epithelial wound-fronts. We identified Leucine Zipper Tumor Suppressor 2 (LZTS2), a factor previously implicated in abscission,...

MOTIVATION: Accurate prediction of protein side-chain conformations is necessary to understand protein folding, protein-protein interactions and facilitate de novo protein design.

The multicomponent Remission Evaluation of Medical Interventions in T2D (REMIT) program has shown reduction of hazard of diabetes relapse by 34-43%, but could benefit from improved ability to scale, spread, and sustain it. This study explored, at the conceptualization phase, patient and health coach perspectives on the acceptability, adoption, feasibility, and appropriateness of a digital REMIT adaptation (diabetes technology enabled coaching (DTEC)). Twelve semi-structured interviews were...

CONCLUSION: All data, protocols, reagent sets, and chemical tools will be made widely available on the AD Knowledge Portal with no intellectual property claims. For more information see www.treatad.org.

CONCLUSION: The awake-prone position was associated with a reduction in the risk of endotracheal intubation and in-hospital mortality. These effects were independent of the context in which the intervention was applied, and no differences were observed between the different waves.

This paper presents a new methodology for generating continuous statistical distributions, integrating the exponentiated odds ratio within the framework of survival analysis. This new method enhances the flexibility and adaptability of distribution models to effectively address the complexities inherent in contemporary datasets. The core of this advancement is illustrated by introducing a particular subfamily, the "Type 2 Gumbel Weibull-G family of distributions". We provide a comprehensive...

Understanding cellular responses to external stimuli is critical for parsing biological mechanisms and advancing therapeutic development. High-content image-based assays provide a cost-effective approach to examine cellular phenotypes induced by diverse interventions, which offers valuable insights into biological processes and cellular states. In this paper, we introduce MorphoDiff, a generative pipeline to predict high-resolution cell morphological responses under different conditions based on...

No abstract

No abstract

Innovative and easy-to-implement strategies are needed to improve the pathogenicity assessment of rare germline missense variants. Somatic cancer driver mutations identified through large-scale tumor sequencing studies often impact genes that are also associated with rare Mendelian disorders. The use of cancer mutation data to aid in the interpretation of germline missense variants, regardless of whether the gene is associated with a hereditary cancer predisposition syndrome or a...

Methyl CpG binding protein 2 (MeCP2) is a chromatin-associated protein that remains enigmatic despite more than 30 years of research, primarily due to the ever-growing list of its molecular functions, and, consequently, its related pathologies. Loss of function MECP2 mutations cause the neurodevelopmental disorder Rett syndrome (RTT); in addition, dysregulation of MeCP2 expression and/or function are involved in numerous other pathologies, but the mechanisms of MeCP2 regulation are unclear....

As the field of artificial intelligence evolves rapidly, these hallmarks are intended to capture fundamental, complementary concepts necessary for the progress and timely adoption of predictive modeling in precision oncology. Through these hallmarks, we hope to establish standards and guidelines that enable the symbiotic development of artificial intelligence and precision oncology.