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Cereal grains are an important source of food and feed. To provide comprehensive spatiotemporal information about biological processes in developing seeds of cultivated barley (Hordeum vulgare L. subsp. vulgare), we performed a transcriptomic study of the embryo, endosperm, and seed maternal tissues collected from grains 4-32 days after pollination. Weighted gene co-expression network and motif enrichment analyses identified specific groups of genes and transcription factors (TFs) potentially...

Understanding microplastic exposure and effects is critical to understanding risk. Here, we used large, in-lake closed-bottom mesocosms to investigate exposure and effects on pelagic freshwater ecosystems. This article provides details about the experimental design and results on the transport of microplastics and exposure to pelagic organisms. Our experiment included three polymers of microplastics (PE, PS, and PET) ranging in density and size. Nominal concentrations ranged from 0 to 29,240...

CONCLUSIONS: In this study, we identify residues important for GCK metabolic stability and conformational dynamics. These residues could be targeted to modulate GCK activity, and thereby affect glucose homeostasis.

The TRIPOD (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis) statement was published in 2015 to provide the minimum reporting recommendations for studies developing or evaluating the performance of a prediction model. Methodological advances in the field of prediction have since included the widespread use of artificial intelligence (AI) powered by machine learning methods to develop prediction models. An update to the TRIPOD statement is thus...

Heterotrimeric G proteins can be regulated by posttranslational modifications, including ubiquitylation. KCTD5, a pentameric substrate receptor protein consisting of an N-terminal BTB domain and a C-terminal domain, engages CUL3 to form the central scaffold of a cullin-RING E3 ligase complex (CRL3^(KCTD5)) that ubiquitylates Gβγ and reduces Gβγ protein levels in cells. The cryo-EM structure of a 5:5:5 KCTD5/CUL3^(NTD)/Gβ(1)γ(2) assembly reveals a highly dynamic complex with rotations of over 60°...

PURPOSE OF REVIEW: Machine learning (ML), a branch of artificial intelligence, is influencing all fields in medicine, with an abundance of work describing its application to adult practice. ML in pediatrics is distinctly unique with clinical, technical, and ethical nuances limiting the direct translation of ML tools developed for adults to pediatric populations. To our knowledge, no work has yet focused on outlining the unique considerations that need to be taken into account when designing and...

CONCLUSION: Ours is the first pan-Canadian IMID assessment of how vaccine history and other factors affect serologic COVID-19 vaccine responses. These findings may help individuals personalize vaccination decisions, including consideration of additional vaccination when >6 months has elapsed since last COVID vaccination/infection.

Recent advances in single-cell sequencing technology have provided opportunities for mathematical modeling of dynamic developmental processes at the single-cell level, such as inferring developmental trajectories. Optimal transport has emerged as a promising theoretical framework for this task by computing pairings between cells from different time points. However, optimal transport methods have limitations in capturing nonlinear trajectories, as they are static and can only infer linear paths...

Exclusive enteral nutrition (EEN) is effective in inducing remission in pediatric Crohn disease (CD). EEN alters the intestinal microbiome, but precise mechanisms are unknown. We hypothesized that pre-diagnosis diet establishes a baseline gut microbiome, which then mediates response to EEN. We analyzed prospectively recorded food frequency questionnaires (FFQs) for pre-diagnosis dietary patterns. Fecal microbiota were sequenced (16SrRNA) at baseline and through an 18-month follow-up period....

This Letter presents the first study of Higgs boson production in association with a vector boson (V=W or Z) in the fully hadronic qqbb final state using data recorded by the ATLAS detector at the LHC in proton-proton collisions at sqrt[s]=13 TeV and corresponding to an integrated luminosity of 137 fb^{-1}. The vector bosons and Higgs bosons are each reconstructed as large-radius jets and tagged using jet substructure techniques. Dedicated tagging algorithms exploiting b-tagging properties are...

The ADP-ribosylation factors (ARFs) and ARF-like (ARLs) GTPases serve as essential molecular switches governing a wide array of cellular processes. In this study, we utilized proximity-dependent biotin identification (BioID) to comprehensively map the interactome of 28 out of 29 ARF and ARL proteins in two cellular models. Through this approach, we identified ∼3000 high-confidence proximal interactors, enabling us to assign subcellular localizations to the family members. Notably, we uncovered...

Salmonella utilizes a type 3 secretion system to translocate virulence proteins (effectors) into host cells during infection¹. The effectors modulate host cell machinery to drive uptake of the bacteria into vacuoles, where they can establish an intracellular replicative niche. A remarkable feature of Salmonella invasion is the formation of actin-rich protuberances (ruffles) on the host cell surface that contribute to bacterial uptake. However, the membrane source for ruffle formation and how...

Reliable estimation of chemical sorption from water to solid phases is an essential prerequisite for reasonable assessments of chemical hazards and risks. However, current fate and exposure models mostly rely on algorithms that lack the capability to quantify chemical sorption resulting from interactions with multiple soil constituents, including amorphous organic matter, carbonaceous organic matter, and mineral matter. Here, we introduce a novel, generic approach that explicitly combines the...

A computational study of the mechanism of hydrogen atom transfer-induced carboxylate elimination from monoacylated 1,2-diol groups in pyranosides is presented. A comprehensive analysis of the 1,2-migration, elimination and fragmentation pathways reveals that concerted elimination via a 7-membered, hydrogen-bonded transition state is favored. Relative rates of elimination inferred from an intramolecular competition experiment are consistent with the trends obtained from the calculations.

Clinical features of 22q11.2 microdeletion syndrome (22q11.2DS) are highly variable between affected individuals and frequently include a subset of conotruncal and aortic arch anomalies. Many are diagnosed with 22q11.2DS when they present as a fetus, newborn or infant with characteristic cardiac findings and subsequently undergo genetic testing. The presence of an aortic arch anomaly with characteristic intracardiac anomalies increases the likelihood that the patient has 22q11.2 DS, but those...

Wastewater surveillance using RT-qPCR has now been widely adopted to track circulating levels of SARS-CoV-2 virus in many sewersheds. The CDC qPCR assays targeting two regions (N1 and N2) within the N gene are commonly used, but a discrepancy between the two biomarkers has been noticed by independent studies using these methods since late 2021. The reason is presumed to be due to mutations in regions targeted by the N1 qPCR probe. In this study, we systematically investigated and unequivocally...

Gene expression is a multi-step transformation of biological information from its storage form (DNA) into functional forms (protein and some RNAs). Regulatory activities at each step of this transformation multiply a single gene into a myriad of proteoforms. Proteogenomics is the study of how genomic and transcriptomic variation creates this proteoform diversity, and is limited by the challenges of modeling the complexities of gene-expression. We therefore created moPepGen, a graph-based...

Ionizing radiation induces cell death in the gastrointestinal (GI) epithelium by activating p53. However, p53 also prevents animal lethality caused by radiation-induced acute GI syndrome. Through single-cell RNA-sequencing of the irradiated mouse small intestine, we find that p53 target genes are specifically enriched in regenerating epithelial cells that undergo fetal-like reversion, including revival stem cells (revSCs) that promote animal survival after severe damage of the GI tract....

MOTIVATION: Supervised deep learning is used to model the complex relationship between genomic sequence and regulatory function. Understanding how these models make predictions can provide biological insight into regulatory functions. Given the complexity of the sequence to regulatory function mapping (the cis-regulatory code), it has been suggested that the genome contains insufficient sequence variation to train models with suitable complexity. Data augmentation is a widely used approach to...

Messenger RNA precursors (pre-mRNA) generally undergo 3' end processing by cleavage and polyadenylation (CPA), which is specified by a polyadenylation site (PAS) and adjacent RNA sequences and regulated by a large variety of core and auxiliary CPA factors. To date, most of the human CPA factors have been discovered through biochemical and proteomic studies. However, genetic identification of the human CPA factors has been hampered by the lack of a reliable genome-wide screening method. We...