Evaluation of Intestinal Barrier Function after Exposure to Digested Pea Ingredients─Food Matrix Effect.

Dietary fibers (DF) are important components of human and animal diets. However, they can decrease protein digestibility and absorption and thus the nutritional value of a food. The aim of this study was to investigate how the form of delivery of pea DF impacted the integrity of the intestinal barrier and, thereby, the potential absorption of molecules.

Uncovering the Hidden: Investigating Influences on Sexual Victimization Among 439 Transgender and Gender Diverse Individuals Behind Bars.

Despite repeated reports of sexual victimization by transgender and gender diverse (TGD) people who are incarcerated, there remains little literature on the source of this sexual assault and the factors that heightened likelihood of experiencing assault while incarcerated. The current research ( = 439) is the first known study aimed at understanding whether individual and state-level factors influence sexual assault while incarcerated. Utilizing data from the 2015 United States Transgender Survey and Malkin and DeJong's (2018) PREA compliance study, analyses were conducted to understand whether individual differences and the number of transgender-specific PREA policies were associated with the likelihood of experiencing sexual assault while incarcerated.

Genetic and physical interactions reveal overlapping and distinct contributions to meiotic double-strand break formation in .

Double-strand breaks (DSBs) are the most deleterious lesions experienced by our genome. Yet, DSBs are intentionally induced during gamete formation to promote the exchange of genetic material between homologous chromosomes. While the conserved topoisomerase-like enzyme Spo11 catalyzes DSBs, additional regulatory proteins-referred to as "Spo11 accessory factors"- regulate the number, timing, and placement of DSBs during early meiotic prophase ensuring that SPO11 does not wreak havoc on the genome.

Understanding and Expanding Zinc Cation/Amine Frustrated Lewis Pair Catalyzed C-H Borylation.

[(NacNac)Zn(DMT)][B(CF)], , (NacNac = {(2,6- PrHC)N(CH)C}CH), DMT = -dimethyl-4-toluidine), was synthesized via two routes starting from either (NacNac)ZnEt or (NacNac)ZnH. Complex is an effective (pre)catalyst for the C-H borylation of (hetero)arenes using catecholborane (CatBH) with H the only byproduct. The scope included weakly activated substrates such as 2-bromothiophene and benzothiophene.

Hydrogel-Based Pre-Clinical Evaluation of Repurposed FDA-Approved Drugs for AML.

In vivo models of acute myeloid leukemia (AML) are low throughput, and standard liquid culture models fail to recapitulate the mechanical and biochemical properties of the extracellular matrix-rich protective bone marrow niche that contributes to drug resistance. Candidate drug discovery in AML requires advanced synthetic platforms to improve our understanding of the impact of mechanical cues on drug sensitivity in AML. By use of a synthetic, self-assembling peptide hydrogel (SAPH) of modifiable stiffness and composition, a 3D model of the bone marrow niche to screen repurposed FDA-approved drugs has been developed and utilized.

An in vitro and in vivo approach to characterize digesta from pigs fed different forms of pea flour.

In vitro models of digestion are useful tools to explore the behavior of dietary fiber sources in gastrointestinal conditions. To evaluate the validity of our digestion model, digesta obtained in vivo and in vitro were characterized and the impact of cell wall integrity on protein bioaccessibility and digestibility evaluated. Six cannulated barrows [Pietrain × (Large White × Landrace)] were included in a 2 × 2 Latin square design where they were fed two diets identical in chemical composition but differing in nutrient bioaccessibility.

Homologous recombination-deficient mutation cluster in tumor suppressor identified by comprehensive analysis of cancer variants.

Mutations in homologous recombination (HR) genes, including , , and the RAD51 paralog , predispose to tumorigenesis and sensitize cancers to DNA-damaging agents and poly(ADP ribose) polymerase inhibitors. However, ∼800 missense variants of unknown significance have been identified for RAD51C alone, impairing cancer risk assessment and therapeutic strategies. Here, we interrogated >50 RAD51C missense variants, finding that mutations in residues conserved with RAD51 strongly predicted HR deficiency and disrupted interactions with other RAD51 paralogs.

The hepatocyte growth factor/mesenchymal epithelial transition factor axis in high-risk pediatric solid tumors and the anti-tumor activity of targeted therapeutic agents.

Clinical trials completed in the last two decades have contributed significantly to the improved overall survival of children with cancer. In spite of these advancements, disease relapse still remains a significant cause of death in this patient population. Often, increasing the intensity of current protocols is not feasible because of cumulative toxicity and development of drug resistance.

The CHARGE syndrome ortholog CHD-7 regulates TGF-β pathways in .

CHARGE syndrome is a complex developmental disorder caused by mutations in the chromodomain helicase DNA-binding protein-7 (CHD7) and characterized by retarded growth and malformations in the heart and nervous system. Despite the public health relevance of this disorder, relevant cellular pathways and targets of CHD7 that relate to disease pathology are still poorly understood. Here we report that chd-7, the nematode ortholog of Chd7, is required for dauer morphogenesis, lifespan determination, stress response, and body size determination.

Zinc catalysed electrophilic C-H borylation of heteroarenes.

Cationic zinc Lewis acids catalyse the C-H borylation of heteroarenes using pinacol borane (HBPin) or catechol borane (HBCat). An electrophile derived from [IDippZnEt][B(CF)] (IDipp = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) combined with ,-dimethyl--toluidine (DMT) proved the most active in terms of C-H borylation scope and yield. Using this combination weakly activated heteroarenes, such as thiophene, were amenable to catalytic C-H borylation using HBCat.

Polymer stealthing and mucin-1 retargeting for enhanced pharmacokinetics of an oncolytic vaccinia virus.

Vaccinia virus (VV) is a powerful tool for cancer treatment with the potential for tumor tropism, efficient cell-to-cell spread, rapid replication in cancer cells, and stimulation of anti-tumor immunity. It has a well-defined safety profile and is being assessed in late-stage clinical trials. However, VV clinical utility is limited by rapid bloodstream neutralization and poor penetration into tumors.

Improved therapeutic antibody delivery to xenograft tumors using cavitation nucleated by gas-entrapping nanoparticles.

Testing ultrasound-mediated cavitation for enhanced delivery of the therapeutic antibody cetuximab to tumors in a mouse model. Tumors with strong EGF receptor expression were grown bilaterally. Cetuximab was coadministered intravenously with cavitation nuclei, consisting of either the ultrasound contrast agent Sonovue or gas-stabilizing nanoscale SonoTran Particles.

A same-day assay predicts apoptotic response to combined BCL-2 and MCL-1 BH3-mimetic targeting in multiple myeloma cells.

Recent advances in treatment options for multiple myeloma (MM) have positive impact on patient survival. However, there is a short fall of rapid and reliable assays that can predict patient response to novel agents. The anti-apoptotic proteins B-cell lymphoma-2 (BCL-2) and myeloid cell leukaemia-1 (MCL-1), are necessary for MM survival, although most myelomas are more dependent on MCL-1.

Morphology of bile salts micelles and mixed micelles with lipolysis products, from scattering techniques and atomistic simulations.

Hypotheses: Bile salts (BS) are biosurfactants released into the small intestine, which play key and contrasting roles in lipid digestion: they adsorb at interfaces and promote the adsorption of digestive enzymes onto fat droplets, while they also remove lipolysis products from that interface, solubilising them into mixed micelles. Small architectural variations on their chemical structure, specifically their bile acid moiety, are hypothesised to underlie these conflicting functionalities, which should be reflected in different aggregation and solubilisation behaviour.

Experiments: The micellisation of two BS, sodium taurocholate (NaTC) and sodium taurodeoxycholate (NaTDC), which differ by one hydroxyl group on the bile acid moiety, was assessed by pyrene fluorescence spectroscopy, and the morphology of aggregates formed in the absence and presence of fatty acids (FA) and monoacylglycerols (MAG) - typical lipolysis products - was resolved by small-angle X-ray/neutron scattering (SAXS, SANS) and molecular dynamics simulations.

Regulation and pharmacological targeting of RAD51 in cancer.

Regulation of homologous recombination (HR) is central for cancer prevention. However, too little HR can increase cancer incidence, whereas too much HR can drive cancer resistance to therapy. Importantly, therapeutics targeting HR deficiency have demonstrated a profound efficacy in the clinic improving patient outcomes, particularly for breast and ovarian cancer.

Gene Family Structure and Function.

Accurate DNA repair and replication are critical for genomic stability and cancer prevention. and its gene family are key regulators of DNA fidelity through diverse roles in double-strand break repair, replication stress, and meiosis. RAD51 is an ATPase that forms a nucleoprotein filament on single-stranded DNA.

Plant Cell Walls: Impact on Nutrient Bioaccessibility and Digestibility.

Cell walls are important structural components of plants, affecting both the bioaccessibility and subsequent digestibility of the nutrients that plant-based foods contain. These supramolecular structures are composed of complex heterogeneous networks primarily consisting of cellulose, and hemicellulosic and pectic polysaccharides. The composition and organization of these different polysaccharides vary depending on the type of plant tissue, imparting them with specific physicochemical properties.

A standardised semi-dynamic in vitro digestion method suitable for food - an international consensus.

The link between food and human health is increasingly a topic of interest. One avenue of study has been to assess food disintegration and interactions within the gastrointestinal tract. In vitro digestion models have been widely used to overcome the constrictions associated with in vivo methodology.

Interactions of bile salts with a dietary fibre, methylcellulose, and impact on lipolysis.

Methylcellulose (MC) has a demonstrated capacity to reduce fat absorption, hypothetically through bile salt (BS) activity inhibition. We investigated MC cholesterol-lowering mechanism, and compared the influence of two BS, sodium taurocholate (NaTC) and sodium taurodeoxycholate (NaTDC), which differ slightly by their architecture and exhibit contrasting functions during lipolysis. BS/MC bulk interactions were investigated by rheology, and BS behaviour at the MC/water interface studied with surface pressure and ellipsometry measurements.

Molecular insights into the behaviour of bile salts at interfaces: a key to their role in lipid digestion.

Hypotheses: Understanding the mechanisms underlying lipolysis is crucial to address the ongoing obesity crisis and associated cardiometabolic disorders. Bile salts (BS), biosurfactants present in the small intestine, play key roles in lipid digestion and absorption. It is hypothesised that their contrasting functionalities - adsorption at oil/water interfaces and shuttling of lipolysis products away from these interfaces - are linked to their structural diversity.

RAD51D splice variants and cancer-associated mutations reveal XRCC2 interaction to be critical for homologous recombination.

The proficiency of cancer cells to repair DNA double-strand breaks (DSBs) by homologous recombination (HR) is a key determinant in predicting response to targeted therapies such as PARP inhibitors. The RAD51 paralogs work as multimeric complexes and act downstream of BRCA1 to facilitate HR. Numerous epidemiological studies have linked RAD51 paralog mutations with hereditary cancer predisposition.

Genetic biomarkers predict response to dual BCL-2 and MCL-1 targeting in acute myeloid leukaemia cells.

Acute myeloid leukaemia (AML) cells often up-regulate pro-survival members of the BCL-2 protein family, such as BCL-2 and MCL-1, to avoid apoptosis. Venetoclax (ABT-199) targets BCL-2 and has shown promising efficacy in AML but over-expression of MCL-1 can cause resistance. A co-operative approach, targeting both BCL-2 and MCL-1 may therefore prove beneficial.