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The cerebellar ventricular zone (VZ) is the primary source of progenitors that generate cerebellar GABAergic neurons, including Purkinje cells (PCs) and interneurons (INs). This study provides detailed characterization of human cerebellar GABAergic neurogenesis using transcriptomic and histopathological analyses and reveals conserved and unique features compared to rodents. We show that the sequential progression of neurogenesis is conserved and occurs before 8 postconception weeks. Notably, PC...

The emergence of COVID-19 in Canada has led to over 4.9 million cases and 59,000 deaths by May 2024. Traditional clinical surveillance metrics (hospital admissions and clinical laboratory-positive cases) were complemented with wastewater and environmental monitoring (WEM) to monitor SARS-CoV-2 incidence. However, challenges in public health integration of WEM persist due to perceived limitations of WEM data quality, potentially driving inconsistent correlations variability and lead times. This...

Clonal haematopoiesis arises when a haematopoietic stem cell (HSC) acquires a mutation that confers a competitive advantage over wild-type HSCs, resulting in its clonal expansion. Individuals with clonal haematopoiesis are at increased risk of developing haematologic neoplasms and other age-related inflammatory illnesses^(1-4). Suppressing the expansion of mutant HSCs may prevent these outcomes; however, such interventions have not yet been identified. The most common clonal haematopoiesis...

The competitive advantage of mutant hematopoietic stem and progenitor cells (HSPCs) underlies clonal hematopoiesis (CH). Drivers of CH include aging and inflammation; however, how CH-mutant cells gain a selective advantage in these contexts is an unresolved question. Using a murine model of CH (Dnmt3a^(R878H/+)), we discover that mutant HSPCs sustain elevated mitochondrial respiration which is associated with their resistance to aging-related changes in the bone marrow microenvironment. Mutant...

The COVID-19 pandemic underscored the critical need to enhance screening capabilities and streamline diagnosis. Point-of-care (POC) tests offer a promising solution by decentralizing testing. We aimed to validate the PLUM device (LSK Technologies Inc.), a portable optical reader, to detect SARS-CoV-2 RNA using direct RT-LAMP targeting the ORF1a and E1 genes and patient antibodies by ELISA. The direct RT-LAMP assays employ nasopharyngeal swabs and bypass RNA extraction protocols through a brief...

Computational methods for assessing the likely impacts of mutations, known as variant effect predictors (VEPs), are widely used in the assessment and interpretation of human genetic variation, as well as in other applications like protein engineering. Many different VEPs have been released, and there is tremendous variability in their underlying algorithms, outputs, and the ways in which the methodologies and predictions are shared. This leads to considerable difficulties for users trying to...

Neurocognitive deficits commonly occur following hemorrhagic stroke in childhood, yet the understanding of recovery patterns and prognostic factors remains limited. Hematoma location, lateralization, volume, and age at injury have been identified as predictors of neurocognitive outcomes. This case review aims to describe and discuss the influence of these factors on neurocognitive outcomes following hemorrhagic stroke in three pediatric cases. Three patients (one female age 13, two males ages 15...

Tracking cellular lineages using genetic barcodes provides insights across biology and has become an important tool. However, barcoding strategies remain ad hoc. We show that elevating barcode insertion probability and thus increasing the average number of barcodes within the cells, adds to the number of traceable lineages but may decrease the accuracy of lineages inference due to reading errors. We establish the trade-off between accuracy in tracing lineages and the total number of traceable...

Background/Objectives: One-third of breast cancer (BC) survivors experience chronic treatment-related pain (CTP) that requires multimodal management strategies, which may include pain self-management behaviors (PSMBs). Most studies exploring PSMBs focus on patients with advanced cancer, who may differ from survivors in their pain management needs and access to resources. This mixed-methods study explored PSMBs of survivors of BC, referral sources, and goals for pain relief, and examined the...

BackgroundMigrant workers in Canada work in the most dangerous industries, with documented difficulties with occupational health and safety (OHS) and workers' compensation (WC). Little is known, however, about migrant workers' experiences with "return-to-work", the ultimate objective of WC for those who recover from their illness or injury.ObjectiveThe objective of this study was to understand migrant workers' "return-to-work" experiences after facing occupational injury/illness for in Québec,...

Optical dynamic nuclear polarization (DNP) offers an attractive approach to enhancing the sensitivity of nuclear magnetic resonance (NMR) spectroscopy. Efficient, optically-generated electron polarization can be leveraged to operate across a broad range of temperatures and magnetic fields, making it particularly appealing for applications requiring high DNP efficiency or spatial resolution. While a large class of systems hold promise for optical DNP, many candidates display both variable...

BACKGROUND: Tuberculosis (TB) remains a significant public health challenge, particularly in rural areas of high-burden countries like China. Active case finding (ACF) and timely treatment have been proven effective in reducing TB prevalence, but the impact on the TB epidemic when employing new technologies in ACF is still unknown. This study aims to evaluate the effectiveness of a comprehensive ACF package utilizing mobile vans equipped with artificial intelligence (AI)-aided radiology and...

A search is performed for dark matter particles produced in association with a resonantly produced pair of b-quarks with 30

Nucleic acid purification is a key step in molecular biology workflows, and especially critical in synthetic biology. Two common techniques are phenol chloroform extraction and silica column adsorption. We have determined that commercial silica columns appear to elute a currently unidentified substance that can inhibit subsequent enzymatic reactions if not sufficiently diluted. To resolve this inhibition, we have developed a novel purification approach in which we achieve simultaneous protein...

Tritrichomonas musculus is a commensal protist colonizing the large intestine of laboratory mice. Parasite colonization reshapes the gut microbiome and modulates mucosal immunity. This parasite is refractory to axenic culture. In order to facilitate functional genomic investigations we assembled a 193.49 Mbp high quality reference genome from FACS-purified parasites recovered from monocolonized mice using an integrated approach that combined long-read (PacBio and Oxford Nanopore) sequencing...

Genetically encoded calcium ion (Ca^(2+)) indicators (GECIs) are widely-used molecular tools for functional imaging of Ca^(2+) dynamics and neuronal activities with single-cell resolution. Here we report the design and development of two far-red fluorescent GECIs, FR-GECO1a and FR-GECO1c, based on the monomeric far-red fluorescent proteins mKelly1 and mKelly2. FR-GECOs have excitation and emission maxima at ~596 nm and ~644 nm, respectively, display large responses to Ca^(2+) in vitro (ΔF/F(0) =...

MOTIVATION: Volumetric electron microscopy (VEM) enables nanoscale resolution three-dimensional imaging of biological samples. Identification and labeling of organelles, cells, and other structures in the image volume is required for image interpretation, but manual labeling is extremely time-consuming. This can be automated using deep learning segmentation algorithms, but these traditionally require substantial manual annotation for training and typically these labeled datasets are unavailable...

The RNA World hypothesis predicts that self-replicating RNAs evolved before DNA genomes and coded proteins. Despite widespread support for the RNA World, self-replicating RNAs have yet to be identified in a natural context, leaving a key 'missing link' for this explanation of the origin of life. Inspired by recent work showing that condensates of charged polymers are capable of catalyzing chemical reactions, we consider a catalytic RNA condensate as a candidate for the self-replicating RNA....

Cell type annotation is crucial in single-cell RNA sequencing data analysis because it enables significant biological discoveries and deepens our understanding of tissue biology. Given the high-dimensional and highly sparse nature of single-cell RNA sequencing data, most existing annotation tools focus on highly variable genes to reduce dimensionality and computational load. However, this approach inevitably results in information loss, potentially weakening the model's generalization...

CONCLUSIONS: In this largest published multiinstitutional longitudinal CMR evaluation of confirmed Multisystem Inflammatory Syndrome in Children patients, the prevalence of ventricular dysfunction and myocardial tissue characterization abnormalities on medium-term follow-up was low. However, a small number of patients had mild residual abnormalities at 6 months and 1 year following hospitalization.