Global amyloid burden enhances network efficiency of tau propagation in the brain.

Background: Amyloid-β (Aβ) and hyperphosphorylated tau are crucial biomarkers in Alzheimer's disease (AD) pathogenesis, interacting synergistically to accelerate disease progression. While Aβ initiates cascades leading to tau hyperphosphorylation and neurofibrillary tangles, PET imaging studies suggest a sequential progression from amyloidosis to tauopathy, closely linked with neurocognitive symptoms.

Objective: To analyze the complex interactions between Aβ and tau in AD using probabilistic graphical models, assessing how regional tau accumulation is influenced by Aβ burden.

Clean and Complete Protein Digestion with an Autolysis Resistant Trypsin for Peptide Mapping.

Peptide mapping requires cleavage of proteins in a predictable fashion so that target protein-specific peptides can be reliably identified and quantified. Trypsin, a commonly used protease in this process, can also undergo self-cleavage or autolysis, thereby reducing the effectivity and even cleavage specificity at lysine and arginine residues. Here, we report highly efficient and reproducible peptide mapping of biotherapeutic monoclonal antibodies.

PodGPT: An audio-augmented large language model for research and education.

The proliferation of scientific podcasts has generated an extensive repository of audio content, rich in specialized terminology, diverse topics, and expert dialogues. Here, we introduce a computational framework designed to enhance large language models (LLMs) by leveraging this informational content from publicly accessible podcast data across science, technology, engineering, mathematics and medical (STEMM) disciplines. This dataset, comprising over 3, 700 hours of audio content, was transcribed to generate over 42 million text tokens.

Evaluation of treatment with human chorionic gonadotropin at transfer of in vitro-produced beef embryos on reproductive outcomes in lactating multiparous Jersey cows after a synchronized ovulation.

Our objective was to evaluate the effect of treatment with human chorionic gonadotropin (hCG) at the time of transfer of in vitro-produced (IVP) beef embryos on pregnancy outcomes in lactating multiparous Jersey cows. Grade 1, stage 7 (expanded blastocyst), IVP beef embryos were produced from black Angus-based dams using 3 proven high-fertility Angus sires and were frozen for direct transfer. In a preliminary experiment, lactating multiparous Jersey cows were randomized to a 2 × 2 factorial arrangement of treatments to test the main effect of recipient synchronization protocol (Double-Ovsynch; DO; n = 169 vs.

Optimizing Messenger RNA Analysis Using Ultra-Wide Pore Size Exclusion Chromatography Columns.

Biopharmaceutical products, in particular messenger ribonucleic acid (mRNA), have the potential to dramatically improve the quality of life for patients suffering from respiratory and infectious diseases, rare genetic disorders, and cancer. However, the quality and safety of such products are particularly critical for patients and require close scrutiny. Key product-related impurities, such as fragments and aggregates, among others, can significantly reduce the efficacy of mRNA therapies.

Single-cell transcriptome analysis reveals secretin as a hallmark of human enteroendocrine cell maturation.

The traditional nomenclature of enteroendocrine cells (EECs), established in 1977, applied the "one cell - one hormone" dogma, which distinguishes subpopulations based on the secretion of a specific hormone. These hormone-specific subpopulations included S cells for secretin (SCT), K cells for glucose-dependent insulinotropic polypeptide (GIP), N cells producing neurotensin (NTS), I cells producing cholecystokinin (CCK), D cells producing somatostatin (SST), and others. In the past 15 years, reinvestigations into murine and human organoid-derived EECs, however, strongly questioned this dogma and established that certain EECs coexpress multiple hormones.

Size exclusion chromatography of biopharmaceutical products: From current practices for proteins to emerging trends for viral vectors, nucleic acids and lipid nanoparticles.

The 21st century has been particularly productive for the biopharmaceutical industry, with the introduction of several classes of innovative therapeutics, such as monoclonal antibodies and related compounds, gene therapy products, and RNA-based modalities. All these new molecules are susceptible to aggregation and fragmentation, which necessitates a size variant analysis for their comprehensive characterization. Size exclusion chromatography (SEC) is one of the reference techniques that can be applied.

Survival analysis on subchondral bone length for total knee replacement.

Objective: Use subchondral bone length (SBL), a new MRI-derived measure that reflects the extent of cartilage loss and bone flattening, to predict the risk of progression to total knee replacement (TKR).

Methods: We employed baseline MRI data from the Osteoarthritis Initiative (OAI), focusing on 760 men and 1214 women with bone marrow lesions (BMLs) and joint space narrowing (JSN) scores, to predict the progression to TKR. To minimize bias from analyzing both knees of a participant, only the knee with a higher Kellgren-Lawrence (KL) grade was considered, given its greater potential need for TKR.

Considering the selectivity of pore size gradient size exclusion chromatography columns.

One of the most significant performance determining variables of a size exclusion column is the pore size of its packing material. This is most definitely the case for assigning the suitability of a given column for differently sized analytes. As technologies for particle and column manufacturing continue to advance, it is worth contemplating the value of more finely controlled manipulation of this parameter.

Monitoring stability indicating impurities and aldehyde content in lipid nanoparticle raw material and formulated drugs.

Lipid nanoparticles (LNPs) are designed to protect and transport sensitive payloads or active pharmaceutical ingredients as part of new therapeutic modalities. As a multi-component particle, a high degree of quality control is necessary to ensure raw materials are free of critical impurities that could adversely impact the drug product. In this study, we demonstrate a reversed phase liquid chromatography method hyphenated with a single quadrupole mass spectrometer (RPLC-MS) as an alternative platform to methods that incorporate evaporative light scattering or charged aerosol detectors in the detection and quantitation of critical impurities associated with LNPs.

Fast and efficient size exclusion chromatography of adeno associated viral vectors with 2.5 micrometer particle low adsorption columns.

More and more transformative gene therapies (GTx) are reaching commercialization stage and many of them use Adeno Associated Viruses (AAVs) as their vector. Being larger than therapeutic antibodies, their size variant analysis poses an analytical challenge that must be addressed to speed up the development processes. Size exclusion chromatography (SEC) can provide critical information on the quality and purity of the product, but its full potential is not yet utilized by currently applied columns that are (i) packed with relatively large particles, (ii) prepared exclusively in large formats and (iii) built using metal hardware that is prone to secondary interactions.

Rapid flapping and fibre-reinforced membrane wings are key to high-performance bat flight.

Bats fly using significantly different wing motions from other fliers, stemming from the complex interplay of their membrane wings' motion and structural properties. Biological studies show that many bats fly at Strouhal numbers, the ratio of flapping to flight speed, 50-150% above the range typically associated with optimal locomotion. We use high-resolution fluid-structure interaction simulations of a bat wing to independently study the role of kinematics and material/structural properties in aerodynamic performance and show that peak propulsive and lift efficiencies for a bat-like wing motion require flapping 66% faster than for a symmetric motion, agreeing with the increased flapping frequency observed in zoological studies.

Effect of postpartum body condition score change on the pregnancy outcomes of lactating Jersey cows inseminated at first service with sexed Jersey or conventional beef semen after a synchronized estrus versus a synchronized ovulation.

Our objective was to compare insemination rate and pregnancies per artificial insemination (P/AI) of lactating Jersey cows inseminated at first service with sexed Jersey or conventional beef semen after submission to a Double-Ovsynch protocol for timed artificial insemination (TAI) versus a protocol to synchronize estrus at similar days in milk (DIM). Secondary objectives were to determine the effect of protocol synchrony and postpartum body condition score (BCS) change on P/AI. Lactating Jersey cows (n = 1,272) were allocated by odd versus even ear tag number, which was randomly allocated within the herd, within parity and semen type for submission to a Double-Ovsynch protocol (DO; n = 707) or a protocol to synchronize estrus (ED; n = 565).

Separation of Plasmid DNA Topological Forms, Messenger RNA, and Lipid Nanoparticle Aggregates Using an Ultrawide Pore Size Exclusion Chromatography Column.

Health authorities have highlighted the need to determine oligonucleotide aggregates. However, existing technologies have limitations that have prevented the reliable analysis of size variants for large nucleic acids and lipid nanoparticles (LNPs). In this work, nucleic acid and LNP aggregation was examined using prototype, low adsorption ultrawide pore size exclusion chromatography (SEC) columns.

The association between insemination eligibility and reproductive performance of nulliparous heifers on subsequent body weight and milk production of primiparous Holstein cows.

The objective of this retrospective cohort study was to determine the association between insemination eligibility and reproductive performance of nulliparous heifers with subsequent body weight (BW) at 30 d in milk (DIM) and milk production at wk 4, 8, and 12 of lactation of primiparous cows. The final data set included 1,849 primiparous Holstein cows from a commercial dairy herd. Data extracted from a commercial dairy herd management software program included parent average predicted transmitting abilities (PTA), bovine respiratory disease (BRD) incidence, pregnancies per artificial insemination (P/AI) at first insemination as nulliparous heifers, BW at 30 DIM, percent mature body weight (%MBW), and mean weekly milk production at wk 4, 8, and 12 of lactation.

Computational tools for inferring transcription factor activity.

Transcription factors (TFs) are essential players in orchestrating the regulatory landscape in cells. Still, their exact modes of action and dependencies on other regulatory aspects remain elusive. Since TFs act cell type-specific and each TF has its own characteristics, untangling their regulatory interactions from an experimental point of view is laborious and convoluted.

High-Throughput Chromatographic Separation of Oligonucleotides: A Proof of Concept Using Ultra-Short Columns.

Ion-pairing reversed-phase liquid chromatography (IP-RPLC) is the reference separation technique for characterizing oligonucleotides (ONs) and their related impurities. The aim of this study was to better understand the retention mechanism of ONs, evaluate the applicability of the linear solvent strength (LSS) retention model, and explore the potential of ultra-short columns having a length of only 5 mm for the separation of model ONs. First, the validity of the LSS model was evaluated for ONs having sizes comprised between 3 and 30 kDa, and the accuracy of retention time predictions was assessed.

Atypical vocal quality in women with the FMR1 premutation: an indicator of impaired sensorimotor control.

Women with the FMR1 premutation are susceptible to motor involvement related to atypical cerebellar function, including risk for developing fragile X tremor ataxia syndrome. Vocal quality analyses are sensitive to subtle differences in motor skills but have not yet been applied to the FMR1 premutation. This study examined whether women with the FMR1 premutation demonstrate differences in vocal quality, and whether such differences relate to FMR1 genetic, executive, motor, or health features of the FMR1 premutation.

Characterization of semen type prevalence and allocation in Holstein and Jersey females in the United States.

Our objective was to characterize semen type prevalence and allocation to inseminate US Holstein and Jersey females by year, parity, service number, and herd size. A secondary objective was to identify the prevalence of beef breed sires selected to create beef × Holstein and beef × Jersey crossbred calves. The final data set included 8,244,653 total inseminations of 4,880,752 Holstein females across 9,155 herds, and 435,267 total inseminations of 266,058 Jersey females across 2,759 herds from October 2019 to July 2021.

A stochastic animal life cycle simulation model for a whole dairy farm system model: Assessing the value of combined heifer and lactating dairy cow reproductive management programs.

This analysis introduces a stochastic herd simulation model and evaluates the estimated reproductive and economic performance of combinations of reproductive management programs for both heifers and lactating cows. The model simulates the growth, reproductive performance, production, and culling for individual animals and integrates individual animal outcomes to represent herd dynamics daily. The model has an extensible structure, allowing for future modification and expansion, and has been integrated into the Ruminant Farm Systems model, a holistic dairy farm simulation model.

Theoretical study on solute migration and band broadening occurring in pressure-enhanced liquid chromatography.

Upon recently studying the use of pressure gradients during liquid chromatography (LC), it was noted that pressure differentials across a column can have a significant impact on peak shape, not just retention as has been noted several times before. Theoretical models and thought experiments were performed here to more carefully study these effects. Two situations have been elucidated.

Studying effective column lengths in liquid chromatography of large biomolecules.

Based on their nature, large molecules tend to exhibit on-off elution such that only a small segment of a column bed participates in their separation. We were intrigued to investigate empirical data on this behavior and to apply a simple method to estimate the length of column bed that is needed to produce an effective separation. Models were derived by rearranging the linear solvent strength (LSS) model equations, and data sets from almost 100 different separation conditions were treated to illustrate effects for various types of solutes as separated by reversed phase (RP), ion-pair reversed phase (IP-RP), ion-exchange (IEX), hydrophobic interaction (HIC) and hydrophilic interaction (HILIC) chromatography.

Insights on further improving fast size exclusion chromatography separations of biopharmaceuticals using 2.1 millimetre column diameters.

Recent trends in the pharmaceutical and biotechnology industries call for the miniaturization of size exclusion chromatography. The thought of such a future has been tantalizing but there are many practical and theoretical considerations that have impeded progress. Here, the capabilities of a narrow bore 2.