Calibration of additional computational tools expands ClinGen recommendation options for variant classification with PP3/BP4 criteria.

Purpose: We previously developed an approach to calibrate computational tools for clinical variant classification, updating recommendations for the reliable use of variant impact predictors to provide evidence strength up to . A new generation of tools using distinctive approaches have since been released, and these methods must be independently calibrated for clinical application.

Method: Using our local posterior probability-based calibration and our established data set of ClinVar pathogenic and benign variants, we determined the strength of evidence provided by three new tools (AlphaMissense, ESM1b, VARITY) and calibrated scores meeting each evidence strength.

Effects of grass species and harvest date on cell wall components and feed efficiency of dairy cows.

There is a balance between DM yield and feed value when choosing types of grasses on a farm depending on the acreages of farmland and types of ruminants to be fed. Therefore, optimisation of the harvest strategy for grass silage is important for profitable dairy farming. Tall fescue has high DM yield and can replace traditional grasses, such as timothy, in Northern Europe in a changing climate as it has been shown to be more drought tolerant.

Assessment of the evidence yield for the calibrated PP3/BP4 computational recommendations.

Purpose: To investigate the number of rare missense variants observed in human genome sequences by ACMG/AMP PP3/BP4 evidence strength, following the ClinGen-calibrated PP3/BP4 computational recommendations.

Methods: Missense variants from the genome sequences of 300 probands from the Rare Genomes Project with suspected rare disease were analyzed using computational prediction tools that were able to reach PP3_Strong and BP4_Moderate evidence strengths (BayesDel, MutPred2, REVEL, and VEST4). The numbers of variants at each evidence strength were analyzed across disease-associated genes and genome-wide.

Phenotype correlations with pathogenic DNA variants in the gene.

-associated polyposis (MAP) is an autosomal recessive disorder where the inheritance of constitutional biallelic pathogenic variants predisposes a person to the development of adenomas and colorectal cancer (CRC). It is also associated with extracolonic and extraintestinal manifestations that may overlap with the phenotype of familial adenomatous polyposis (FAP). Currently, there are discrepancies in the literature regarding whether certain phenotypes are truly associated with MAP.

Assessment of the evidence yield for the calibrated PP3/BP4 computational recommendations.

Purpose: To investigate the number of rare missense variants observed in human genome sequences by ACMG/AMP PP3/BP4 evidence strength, following the calibrated PP3/BP4 computational recommendations.

Methods: Missense variants from the genome sequences of 300 probands from the Rare Genomes Project with suspected rare disease were analyzed using computational prediction tools able to reach PP3_Strong and BP4_Moderate evidence strengths (BayesDel, MutPred2, REVEL, and VEST4). The numbers of variants at each evidence strength were analyzed across disease-associated genes and genome-wide.

Transcriptomic Analysis Pipeline (TAP) for quality control and functional assessment of transcriptomes.

Background: RNA-sequencing (RNA-seq) has revolutionized the exploration of biological mechanisms, shedding light on the roles of non-coding RNAs, including long non-coding RNAs (lncRNAs), across various biological processes, including stress responses. Despite these advancements, there remains a gap in our understanding of the implications of different RNA-seq library protocols on comprehensive lncRNA expression analysis, particularly in non-mammalian organisms.

Results: In this study, we sought to bridge this knowledge gap by investigating lncRNA expression patterns in under thermal stress conditions.

Transcriptional Regulation of Reproductive Diapause in the Convergent Lady Beetle, .

Diapause is an alternate development program that synchronizes an insect's life cycle with seasonally abundant resources and ensures survival in unfavorable conditions. The physiological basis of diapause has been well characterized, but the molecular mechanisms regulating it are still being elucidated. Here, we present a transcriptome and quantify transcript expression during diapause in the convergent lady beetle .

Relating Mobility of dsRNA in Nanoporous Silica Particles to Loading and Release Behavior.

Nanoparticle delivery of polynucleic acids traditionally relies on the modulation of surface interactions to achieve loading and release. This work investigates the additional role of confinement in mobility of dsRNA (84 and 282 base pair (bp) sequences of ) as a function of silica nanopore size (nonporous, 3.9, 8.

Effects of harvest date and grass species on silage cell wall components and lactation performance of dairy cows.

This study evaluated the effect of harvest date and forage species on the concentration of hydroxycinnamic acids in silage and its relationship to dairy cow performance. Tall fescue and timothy were harvested at a regular date on June 27 and July 8, respectively, or at a late date on July 8 and 25, respectively, in the first regrowth. Forage was treated with a salt-based additive and ensiled in hard-pressed round bales.

Effect of Confinement in Nanopores on RNA Interactions with Functionalized Mesoporous Silica Nanoparticles.

Amine-functionalized mesoporous silica nanoparticles (MSNPAs) are ideal carriers for oligonucleotides for gene delivery and RNA interference. This investigation examines the thermodynamic driving force of interactions of double-stranded (ds) RNA with MSNPAs as a function of RNA length (84 and 282 base pair) and particle pore diameter (nonporous, 2.7, 4.

Self-initiated lifestyle interventions lead to potential insight into an effective, alternative, non-surgical therapy for mitochondrial disease associated multiple symmetric lipomatosis.

Background: A 56-year-old female, diagnosed as a carrier of the mitochondrial DNA mutation (MTTK c.8344A > G) associated with the MERRF (myoclonic epilepsy with ragged red fibers) syndrome, presented with a relatively uncommon but well-known phenotypic manifestation: severe multiple symmetric lipomatosis (MSL). After surgical resection of three kilograms of upper mid-back lipomatous tissue, the patient experienced a significant decline in her functional capacity and quality of life, which ultimately resulted in her placement on long-term disability.

The Effect of Feeding Roughages of Varying Digestibility Prepartum on Energy Status and Metabolic Profiles in Beef Cows around Parturition.

Resource efficient winter-feeding of mature pregnant beef cows requires knowledge of how different roughage-based feeding strategies affect cow intake and energy status. Four diets based on traditional timothy-meadow fescue silage (TM), festulolium silage plus urea (FE), reed canarygrass silage (RC) or barley straw supplemented with urea and rapeseed meal (BR), were fed ad libitum for 16 weeks prepartum to 36 Hereford cows. Postpartum, cows were fed the same diet before release on pasture.

Nonlabeling and quantitative assessment of chondrocyte viability in articular cartilage with intrinsic nonlinear optical signatures.

Unlabelled: Chondrocyte viability is a crucial factor for evaluating cartilage health. Most prevalent cell viability assays rely on dyes and are not applicable for or longitudinal studies. Here we demonstrated that the two-photon excited autofluorescence and second harmonic generation microscopy provided high-resolution imaging of cartilage tissue and distinguished live/dead chondrocytes by visual assessment.

Evidence for a rapid cold hardening response in cultured S2 cells.

The ability to quickly respond to changes in environmental temperature is critical for organisms living in thermally variable environments. To cope with sudden drops in temperature, insects and other ectotherms are capable of rapid cold hardening (RCH), in which mild chilling significantly enhances cold tolerance within minutes. While the ecological significance of RCH is well established, the mechanisms underlying RCH are still poorly understood.

Enolase and dipeptidyl peptidase IV protein sub-unit vaccines are not protective against a lethal Streptococcus suis serotype 2 challenge in a mouse model of infection.

Background: Streptococcus suis is a major swine pathogen causing arthritis, meningitis and sudden death in post-weaning piglets and is also a zoonotic agent. S. suis comprises 35 different serotypes of which the serotype 2 is the most prevalent in both pigs and humans.

Plasma Neutrophil Gelatinase-Associated Lipocalin Is Associated With Acute Kidney Injury and Clinical Outcomes in Neonates Undergoing Cardiopulmonary Bypass.

Objectives: Acute kidney injury is a frequent complication following neonatal cardiac surgery and is associated with significant morbidity and mortality. The objectives of this study were to determine if plasma neutrophil gelatinase-associated lipocalin levels were associated with acute kidney injury and clinical outcomes in neonates with congenital heart disease undergoing cardiopulmonary bypass.

Design: Retrospective single-center observational study.

Digestibility and protein utilization in wethers fed whole-crop barley or grass silages harvested at different maturity stages, with or without protein supplementation1.

Effects of whole-crop barley and grass silages harvested at different maturity stages, with or without protein supplementation, on intake, in vivo digestibility, feces characteristics, and protein utilization in wethers were evaluated. Whole-crop barley silage harvested at heading stage (BH) and at medium milk stage (BM), grass silage (GE) taken at the flag leaf-early heading stage, and grass silage (GL) taken at medium-late heading stage were fed to eight wethers in two 4 × 4 Latin squares. Wethers in one square were fed supplementary rapeseed meal.

Elevated Wall Tension Leads to Reduced miR-133a in the Thoracic Aorta by Exosome Release.

Background Reduced miR-133a was previously found to be associated with thoracic aortic ( TA ) dilation, as seen in aneurysm disease. Because wall tension increases with vessel diameter (Law of Laplace), this study tested the hypothesis that elevated tension led to the reduction of miR-133a in the TA . Methods and Results Elevated tension (1.

Intake and feed utilization in two breeds of pregnant beef cows fed forages with high-fiber concentrations.

Hereford and Charolais beef cows (n = 24 per breed) were used to study the effect of breed and to evaluate late-cut reed canarygrass (RC) and whole-crop oats plus urea (WCO) compared with late-cut timothy (TG) with respect to feed intake and digestibility, rumination time, fecal particle size (PS) distribution, N excretion, and ruminal microbial CP production (MCP). The TG and RC were cut at flowering and WCO at hard dough stage of maturity. Cows were group-housed, 6 groups per breed, and fed 3 diets ad libitum in 3 periods.