A Quantitative First Passage Time Model for Tubular Microfluidic Immunoassays.

Solid-phase immunosorbent reactions, such as ELISA, are widely used for detecting, identifying, and quantifying protein markers. However, traditional centimeter scale well-based immunoreactors suffer from low surface-to-volume (S/V) ratios, leading to large sample consumption and a long assay time. Microfluidic technologies, particularly tubular microfluidic immunoreactors, have emerged as promising alternatives due to their high S/V ratios.

Rapid and Non-Targeted Qualitative and Quantitative Detection of miRNA in Complex Biological Samples Using Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry with a 3-Aminoquinoline and 2',4',6'-Trihydroxyacetophenone Ionic Liquid Matrix.

A novel ionic liquid MALDI matrix, 3-aminoquinoline/2',4',6'-trihydroxyacetophenone monohydrate (3-AQ/THAP), was developed for the rapid qualitative and quantitative detection of miRNA from biological samples. Compared to the traditional matrix 2,5-dihydroxybenzoic acid (DHB) and previously reported oligonucleotide-specific matrices, such as 3-aminopicolinic acid (3-APA), 3-hydroxypicolinic acid (3-HPA), and 6-aza-2-thiothymine (ATT), the 3-AQ/THAP matrix offers several advantages. It produces fewer alkali metal adduct peaks, exhibits higher sensitivity, and ensures better spot-to-spot repeatability.

Activation of the conserved Hippo kinases by inflammasome-triggered proteolytic cleavage controls programmed cell death in macrophages.

The mammalian Hippo kinases, MST1 and MST2, regulate organ development and suppress tumor formation by balancing cell proliferation and death. In macrophages, inflammasomes detect molecular patterns from invading pathogens or damaged host cells and trigger programmed cell death. In addition to lytic pyroptosis, the signatures associated with apoptosis are induced by inflammasome activation, but how the inflammasomes coordinate different cell death processes remains unclear.

Optimal strategies for correcting merotelic chromosome attachments in anaphase.

Accurate chromosome segregation in mitosis depends on proper connections of sister chromatids, through microtubules, to the opposite poles of the early mitotic spindle. Transiently, many inaccurate connections are formed and rapidly corrected throughout the mitotic stages, but a small number of merotelic connections, in which a chromatid is connected to both spindle poles, remain lagging at the spindle's equator in anaphase. Most of the lagging chromatids are eventually moved to one or the other pole, likely by a combination of microtubules' turnover and the brute force of pulling by the microtubules' majority from the one pole against the microtubules' minority from the other pole.

Global natural history infrastructure requires international solidarity, support, and investment in local capacity.

Amid global challenges like climate change, extinctions, and disease epidemics, science and society require nuanced, international solutions that are grounded in robust, interdisciplinary perspectives and datasets that span deep time. Natural history collections, from modern biological specimens to the archaeological and fossil records, are crucial tools for understanding cultural and biological processes that shape our modern world. At the same time, natural history collections in low and middle-income countries are at-risk and underresourced, imperiling efforts to build the infrastructure and scientific capacity necessary to tackle critical challenges.

Ancient genomics and the origin, dispersal, and development of domestic sheep.

The origins and prehistory of domestic sheep () are incompletely understood; to address this, we generated data from 118 ancient genomes spanning 12,000 years sampled from across Eurasia. Genomes from Central Türkiye ~8000 BCE are genetically proximal to the domestic origins of sheep but do not fully explain the ancestry of later populations, suggesting a mosaic of wild ancestries. Genomic signatures indicate selection by ancient herders for pigmentation patterns, hornedness, and growth rate.

Energetic constraints drive the decline of a sentinel polar bear population.

Human-driven Arctic warming and resulting sea ice loss have been associated with declines in several polar bear populations. However, quantifying how individual responses to environmental change integrate and scale to influence population dynamics in polar bears has yet to be achieved. We developed an individual-based bioenergetic model and hindcast population dynamics across 42 years of observed sea ice conditions in Western Hudson Bay, a region undergoing rapid environmental change.

Tolerance mechanisms in polysaccharide biosynthesis: Implications for undecaprenol phosphate recycling in Escherichia coli and Shigella flexneri.

Bacterial polysaccharide synthesis is catalysed on the universal lipid carrier, undecaprenol phosphate (UndP). The cellular UndP pool is shared by different polysaccharide synthesis pathways including peptidoglycan biogenesis. Disruptions in cytosolic polysaccharide synthesis steps are detrimental to bacterial survival due to effects on UndP recycling.

An untargeted metabolomic analysis of acute AFB1 treatment in liver, breast, and lung cells.

Aflatoxin B1 (AFB1) is a class 1 carcinogen and mycotoxin known to contribute to the development of hepatocellular carcinoma (HCC), growth impairment, altered immune system modulation, and malnutrition. AFB1 is synthesized by Aspergillus flavus and is known to widely contaminate foodstuffs, particularly maize, wheat, and groundnuts. The mechanism in which AFB1 causes genetic mutations has been well studied, however its metabolomic effects remained largely unknown.

Patterns of microbial contamination on Northumberland Strait shores.

The re-emergence of episodic faecal contamination of Parlee and Murray Corner beaches, on the Northumberland Strait of New Brunswick, Canada, in 2017, raised renewed community concerns on the health, environmental and tourism sustainability of these community resources, and led to creation of an Integrated Watershed Management Plan for the Shediac Bay Watershed (October 2021). In response we have to date compiled, curated and made accessible 205,772 microbial water quality data records spanning over 80 years from Southeastern New Brunswick and the Northumberland Strait. This dataset derives in large part from Shellfish Surveys completed by Environment and Climate Change Canada, along with data generated by multiple government agencies, Non-Governmental Organizations and citizen science sources.

Investigating the miRNA-mRNA interactome of human trabecular meshwork cells treated with TGF-β1 provides insights into the pathogenesis of pseudoexfoliation glaucoma.

Pseudoexfoliation glaucoma is a severe form of secondary open angle glaucoma and is associated with activation of the TGF-β pathway by TGF-β1. MicroRNAs (miRNAs) are small non-coding RNA species that are involved in regulation of mRNA expression and translation. To investigate what glaucomatous changes occur in the trabecular meshwork and how these changes may be regulated by miRNAs, we performed a bioinformatics analysis resulting in a miRNA-mRNA interactome.

Prevalence and antimicrobial resistant Campylobacter spp. in broiler chicken carcasses and hygiene practises in informal urban markets in a low-income setting.

Campylobacteriosis is one of the most commonly reported foodborne diseases and is of particular importance in low-income countries. More data is needed to better understand the epidemiology of Campylobacter spp. in food sold at informal markets, where most people in low-income countries buy their food.

Food hardness preference reveals multisensory contributions of fly larval gustatory organs in behaviour and physiology.

Food presents a multisensory experience, with visual, taste, and olfactory cues being important in allowing an animal to determine the safety and nutritional value of a given substance. Texture, however, remains a surprisingly unexplored aspect, despite providing key information about the state of the food through properties such as hardness, liquidity, and granularity. Food perception is achieved by specialised sensory neurons, which themselves are defined by the receptor genes they express.

Graph contrastive learning of subcellular-resolution spatial transcriptomics improves cell type annotation and reveals critical molecular pathways.

Imaging-based spatial transcriptomics (iST), such as MERFISH, CosMx SMI, and Xenium, quantify gene expression level across cells in space, but more importantly, they directly reveal the subcellular distribution of RNA transcripts at the single-molecule resolution. The subcellular localization of RNA molecules plays a crucial role in the compartmentalization-dependent regulation of genes within individual cells. Understanding the intracellular spatial distribution of RNA for a particular cell type thus not only improves the characterization of cell identity but also is of paramount importance in elucidating unique subcellular regulatory mechanisms specific to the cell type.

A comprehensive benchmarking for evaluating TCR embeddings in modeling TCR-epitope interactions.

The complexity of T cell receptor (TCR) sequences, particularly within the complementarity-determining region 3 (CDR3), requires efficient embedding methods for applying machine learning to immunology. While various TCR CDR3 embedding strategies have been proposed, the absence of their systematic evaluations created perplexity in the community. Here, we extracted CDR3 embedding models from 19 existing methods and benchmarked these models with four curated datasets by accessing their impact on the performance of TCR downstream tasks, including TCR-epitope binding affinity prediction, epitope-specific TCR identification, TCR clustering, and visualization analysis.

Revised Process for ACNS Guidelines Development.

The development of clinical practice guidelines is an evolving field. In response to the need for consistent, evidence-based medical practice, the American Clinical Neurophysiology Society identified the need to update the Society's guideline development process. The American Clinical Neurophysiology Society Guidelines Committee created an action plan with the goal of improving transparency and rigor for future guidelines and bringing existing guidelines to current standards.

Ophthalmic Complications Associated With the Antidiabetic Drugs Semaglutide and Tirzepatide.

Importance: Nearly 2% of the US population received a prescription for semaglutide in 2023. There has been a recent concern that this drug and other similar medications may be associated with ophthalmic complications.

Objective: To report ophthalmic complications associated with the use of semaglutide or tirzepatide.

The Promising Biological Role of Postbiotics in Treating Human Infertility.

Infertility poses a global challenge that impacts a significant proportion of the populace. Presently, there is a substantial emphasis on investigating the potential of probiotics and their derivatives, called postbiotics, as an alternative therapeutic strategy for addressing infertility. The term of "postbiotics" refers to compounds including peptides, enzymes, teichoic acids, and muropeptides derived from peptidoglycans, polysaccharides, proteins, and organic acids that are excreted by living bacteria or released after bacterial lysis.

Clinical presentation, outcomes and risk of relapses of lupus podocytopathy in a multicentre Italian cohort.

Background: In an Italian cohort of lupus podocytopathy patients, we aimed to characterize the presenting features, therapy, and outcomes, and explore differences between relapsing and non-relapsing patients.

Methods: We identified 29 patients with lupus podocytopathy from 1994 to 2023 in 11 Italian Nephrology/Rheumatology Units, and divided them into two groups: relapsing and non-relapsing. Given the limited sample size, a p-value ≤ 0.

The impact of a secondary, rare, non-pathogenic PKD1 variant on disease progression in autosomal dominant polycystic kidney disease.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is caused primarily by pathogenic variants in the PKD1 and PKD2 genes. Although the type of ADPKD variant can influence disease severity, rare, hypomorphic PKD1 variants have also been reported to modify disease severity or cause biallelic ADPKD. This study examines whether rare, additional, potentially protein-altering, non-pathogenic PKD1 variants contribute to ADPKD phenotypic outcomes.

Computational Elucidation of Hub Genes and Pathways Correlated with the Development of 5-Fluorouracil Resistance in HCT 116 Colorectal Carcinoma Cell Line.

Colorectal cancer (CRC) is the third most deadly cancer diagnosed in both men and women. 5-Fluorouracil (5-FU) treatment frequently causes the CRC cells to become chemoresistance, which has a negative impact on prognosis. Using bioinformatic techniques, this work describes important genes and biological pathways linked to 5-FU resistance in CRC cells.

Ovarian function after COVID-19: long-term effects and vaccine safety in ART patients.

Purpose: This study aimed to evaluate the long-term impact of mild COVID-19 infection and COVID-19 vaccination on ovarian function in patients undergoing assisted reproductive technology (ART). Specifically, we assessed ovarian outcomes between 9 and 18 months post-infection and investigated the effects of COVID-19 vaccines (inactivated virus and adenovirus) on reproductive parameters.

Methods: The study included two objectives: (a) examining ovarian function in post-COVID-19 patients (9-18 months post-infection) compared to a control group and (b) comparing reproductive outcomes in vaccinated versus unvaccinated patients.

First-line biologics as a treatment for ulcerative colitis: a multicenter randomized control study.

Background: Despite the availability of several biologics for ulcerative colitis (UC), there remains a critical need to identify first-line treatment biologics. The superiority of infliximab (IFX) over vedolizumab (VED) and ustekinumab (UST) was evaluated as initial UC treatments in patients with biologic-naïve UC.

Methods: This multicenter, randomized control trial was conducted across 20 Japanese medical institutions.