Single-cell transcriptomic analysis of the human vascular atlas provides new insights into vasorelaxation redundancy and heterogeneity.

Background: Endothelial cells (ECs) induce vascular smooth muscle cells (VSMCs) relaxation via nitric oxide (NO), prostacyclin (PGI₂) and hyperpolarizing factors. Recent whole-genomic, single-cell transcriptomic analysis of human vascular cells has revealed angiotypic heterogeneity. However, it remains unknown whether vasorelaxant mediators reiterate this pattern.

Feed restriction as a model for small intestinal permeability in nursery pigs.

Reduced feed intake is a hallmark of many animal diseases and environmental conditions and has been shown to cause intestinal barrier dysfunction. As there are several markers and assays to evaluate intestinal barrier function, feed restriction may present a potential model to validate and compare multiple in vivo, ex vivo, and tissue markers of intestinal integrity. Forty-eight barrows (9.

Acute enhanced liquid aspirin administration improves performance and intestinal function in nursery pigs.

Aspirin (acetylsalicylic acid) is a nonsteroidal anti-inflammatory drug which has been a widely used analgesic for pain relief as well as an anti-inflammatory medication. However, it also causes negative effects on the gastrointestinal (GI) tract including GI bleeding, peptic ulcers, and can also impact the small intestine. Enhanced liquid aspirin (ELA) contains a combination of a salicylate compound, glycerin, triacetate, and saccharin which is more stable than aspirin alone and may reduce negative effects on the GI tract, while still exerting positive effects on inflammatory processes.

Energy digestibility in broilers and poult performance when fed palm or soybean oil with or without glyceryl monolaurate.

Two trials were conducted to determine interactive effects between lipid source (palm oil, PO versus soybean oil, SO) and emulsifier addition (none versus glycerol monolaurate-GML) on apparent total tract digestibility (ATTD) of gross energy (GE) in broilers and growth performance in poults. In trial 1, 0.05 % GML addition had no impact on the ATTD of GE of SO but improved the ATTD of PO from 77.

Clinical profile of paediatric acute rheumatic fever and rheumatic heart disease in Western Australia: 1987 to 2020.

Aim: To describe the clinical profile of acute rheumatic fever (ARF) presentations to paediatric cardiology tertiary services in Western Australia (WA).

Methods: A retrospective clinical audit of individuals with confirmed ARF referred to the only paediatric tertiary cardiac service in WA (1 January 1987 to 31 December 2020). Comparisons between inpatient, outpatient, remote and non-remote groups were assessed.

Dietary isoacids effects on growth, nitrogen, and energy digestibility, and fecal volatile fatty acids and microbial ecology in finishing pigs.

Isoacids are branched ketoacids which when fed to ruminants have been shown to enhance the growth of fiber-digesting organisms. Ninety finishing gilts were individually fed dietary treatments consisting of diet type: corn-soybean meal (CSBM), a diet containing 40% distillers dried grains with solubles (DDGS), or a diet containing 40% sugar beet pulp (SBP); in combination with either no feed additive (CNT), the addition of 0.50% isobutyrate (IB), or the addition of a 0.

Tonsils at Telethon: developing a standardised collection of tonsil photographs for group A streptococcal (GAS) research.

Introduction: Group A streptococcus (GAS) infections, such as pharyngitis and impetigo, can lead to rheumatic fever and rheumatic heart disease (RHD). Australian Aboriginal and Torres Strait Islander populations experience high rates of RHD and GAS skin infection, yet rates of GAS pharyngitis are unclear. Anecdotally, clinical presentations of pharyngitis, including tonsillar hypertrophy and sore throat, are uncommon.

Collaborative Recognition of Wellbeing Needs: A Novel Approach to Universal Psychosocial Screening on the Neonatal Unit.

Universal screening for the psychological needs of families in neonatal care is internationally recommended, but is not routinely practiced in the United Kingdom (UK). The present quality improvement project explores the clinical and operational feasibility of a novel approach to universal screening on a neonatal intensive care unit in the UK. The approach to screening taken adopts collaborative, strengths-based and dialogical methods for recognising the psychological needs of families whose baby is in hospital.

Effects of dietary protein level on intestinal function and inflammation in nursery pigs.

High crude protein (CP; 21% to 26%) diets fed during the first 21 to 28 d postweaning are viewed negatively because of a perceived increase in the incidence rates of diarrhea due to increased intestinal protein fermentation and/or augmented enteric pathogen burden. This is thought to antagonize nursery pig health and growth performance. Therefore, our objective was to evaluate the impact of low vs.

Specialty pharmacy: Incorporating workflow management and medication access into pharmacy lecture and laboratory courses.

Background And Purpose: The purpose of this study was to implement and evaluate a specialty pharmacy workshop across pharmacy management and skills lab courses.

Educational Activity And Setting: A specialty pharmacy workshop was developed and implemented. The lecture cohort (fall 2019) consisted of a 90-min lecture in pharmacy management.

Soluble corn fiber, resistant corn starch, and protected butyrate effects on performance, gastrointestinal volatile fatty acids, and apparent total-tract digestibility of calcium and phosphorus in nursery pigs.

An experiment was conducted to determine how feeding calcium (Ca)-deficient diet would affect gastrointestinal pH and volatile fatty acids (VFAs), Ca digestibility, bone mineral density (BMD), and performance in nursery pigs; and if supplementation of nondigestible oligosaccharides would affect these same parameters. In total, 240 weaned pigs (BW = 7.1 kg) were placed into 80 pens with 3 pigs/pen.

Translation initiation of leaderless and polycistronic transcripts in mammalian mitochondria.

The synthesis of mitochondrial OXPHOS complexes is central to cellular metabolism, yet many molecular details of mitochondrial translation remain elusive. It has been commonly held view that translation initiation in human mitochondria proceeded in a manner similar to bacterial systems, with the mitoribosomal small subunit bound to the initiation factors, mtIF2 and mtIF3, along with initiator tRNA and an mRNA. However, unlike in bacteria, most human mitochondrial mRNAs lack 5' leader sequences that can mediate small subunit binding, raising the question of how leaderless mRNAs are recognized by mitoribosomes.

Effects of short-chain fatty acids on intestinal function in an enteroid model of hypoxia.

The healthy GI tract is physiologically hypoxic, but this may be perturbed by certain acute and chronic stressors that reduce oxygen availability systemically. Short-chain fatty acids have been shown to have beneficial effects on intestinal barrier function and inflammation. Therefore, our objective was to see whether short-chain fatty acids (SCFA) would improve GI barrier function, reduce production of pro-inflammatory cytokines, and increase the expression of genes regulating GI barrier function in enteroids exposed to hypoxia.

PANTHER: AZD8931, inhibitor of EGFR, ERBB2 and ERBB3 signalling, combined with FOLFIRI: a Phase I/II study to determine the importance of schedule and activity in colorectal cancer.

Background: Epidermal growth factor receptor (EGFR) is a therapeutic target to which HER2/HER3 activation may contribute resistance. This Phase I/II study examined the toxicity and efficacy of high-dose pulsed AZD8931, an EGFR/HER2/HER3 inhibitor, combined with chemotherapy, in metastatic colorectal cancer (CRC).

Methods: Treatment-naive patients received 4-day pulses of AZD8931 with irinotecan/5-FU (FOLFIRI) in a Phase I/II single-arm trial.

ANGEL2 phosphatase activity is required for non-canonical mitochondrial RNA processing.

Canonical RNA processing in mammalian mitochondria is defined by tRNAs acting as recognition sites for nucleases to release flanking transcripts. The relevant factors, their structures, and mechanism are well described, but not all mitochondrial transcripts are punctuated by tRNAs, and their mode of processing has remained unsolved. Using Drosophila and mouse models, we demonstrate that non-canonical processing results in the formation of 3' phosphates, and that phosphatase activity by the carbon catabolite repressor 4 domain-containing family member ANGEL2 is required for their hydrolysis.

Evaluation of digestively resistant or soluble fibers, short- and medium-chain fatty acids, trace minerals, and antibiotics in nonchallenged nursery pigs on performance, digestibility, and intestinal integrity.

Three experiments (EXP) were conducted to determine the effect of feed additives on performance, intestinal integrity, gastrointestinal volatile fatty acids (VFA), and energy and nutrient digestion in nonchallenged nursery pigs. In EXP 1, 480 pigs (6.36-kg body weight, BW) were placed into 96 pens with 5 pigs/pen, and allotted to 1 of 10 dietary treatments: 1) negative control containing no feed additive (NC), 2) NC + 44 mg chlortetracycline and 38.

Human iPSC colon organoid function is improved by exposure to fecal fermentates.

The host-microbe interaction is critical for intestinal homeostasis. By-products from microbial metabolism of unabsorbed dietary components have been studied increasingly as potential contributors to health and disease. In vitro fermentation systems provide a way to simulate microbial activity and by-product production of the colon using human fecal samples.

Enhanced System Robustness of Asynchronous BCI in Augmented Reality Using Steady-State Motion Visual Evoked Potential.

This study evaluated the effect of change in background on steady state visually evoked potentials (SSVEP) and steady state motion visually evoked potentials (SSMVEP) based brain computer interfaces (BCI) in a small-profile augmented reality (AR) headset. A four target SSVEP and SSMVEP BCI was implemented using the Cognixion AR headset prototype. An active (AB) and a non-active background (NB) were evaluated.

Expression of SARS-CoV-2 entry factors, electrolyte, and mineral transporters in different mouse intestinal epithelial cell types.

Angiotensin-converting enzyme 2 (ACE2) and transmembrane proteases (TMPRSS) are multifunctional proteins required for SARS-CoV-2 infection or for amino acid (AA) transport, and are abundantly expressed in mammalian small intestine, but the identity of the intestinal cell type(s) and sites of expression are unclear. Here we determined expression of SARS-CoV-2 entry factors in different cell types and then compared it to that of representative AA, electrolyte, and mineral transporters. We tested the hypothesis that SARS-CoV-2, AA, electrolyte, and mineral transporters are expressed heterogeneously in different intestinal cell types by making mouse enteroids enriched in enterocytes (ENT), goblet (GOB), Paneth (PAN), or stem (ISC) cells.

Dual Systems for Enhancing Control of Protein Activity through Induced Dimerization Approaches.

To reveal the underpinnings of complex biological systems, a variety of approaches have been developed that allow switchable control of protein function. One powerful approach for switchable control is the use of inducible dimerization systems, which can be configured to control activity of a target protein upon induced dimerization triggered by chemicals or light. Individually, many inducible dimerization systems suffer from pre-defined dynamic ranges and overwhelming sensitivity to expression level and cellular context.

A modular tool to query and inducibly disrupt biomolecular condensates.

Dynamic membraneless compartments formed by protein condensates have multifunctional roles in cellular biology. Tools that inducibly trigger condensate formation have been useful for exploring their cellular function, however, there are few tools that provide inducible control over condensate disruption. To address this need we developed DisCo (Disassembly of Condensates), which relies on the use of chemical dimerizers to inducibly recruit a ligand to the condensate-forming protein, triggering condensate dissociation.

Elucidating the cellular dynamics of the brain with single-cell RNA sequencing.

Single-cell RNA-sequencing (scRNA-seq) has emerged in recent years as a breakthrough technology to understand RNA metabolism at cellular resolution. In addition to allowing new cell types and states to be identified, scRNA-seq can permit cell-type specific differential gene expression changes, pre-mRNA processing events, gene regulatory networks and single-cell developmental trajectories to be uncovered. More recently, a new wave of multi-omic adaptations and complementary spatial transcriptomics workflows have been developed that facilitate the collection of even more holistic information from individual cells.

Human GTPBP5 is involved in the late stage of mitoribosome large subunit assembly.

Human mitoribosomes are macromolecular complexes essential for translation of 11 mitochondrial mRNAs. The large and the small mitoribosomal subunits undergo a multistep maturation process that requires the involvement of several factors. Among these factors, GTP-binding proteins (GTPBPs) play an important role as GTP hydrolysis can provide energy throughout the assembly stages.