A5058226651- Reflective Practices in Education
- Pancreatic function and diabetes
- Innovations in Medical Education
- Endoplasmic Reticulum Stress and Disease
- DNA and Nucleic Acid Chemistry
- Evaluation of Teaching Practices
- Higher Education Learning Practices
- RNA Interference and Gene Delivery
- Photoreceptor and optogenetics research
- Advanced biosensing and bioanalysis techniques
- Retinal Development and Disorders
- Receptor Mechanisms and Signaling
- Kruppel-like factors research
- Lipid metabolism and biosynthesis
- Diet, Metabolism, and Disease
- RNA Research and Splicing
- Suicide and Self-Harm Studies
- Empathy and Medical Education
- Patient Satisfaction in Healthcare
- Innovative Teaching and Learning Methods
- Microbial Metabolic Engineering and Bioproduction
- Epigenetics and DNA Methylation
- Hemoglobinopathies and Related Disorders
- Genetics and Neurodevelopmental Disorders
- Higher Education Practises and Engagement
Ionis Pharmaceuticals (United States)
2013-2025
Sanford Burnham Prebys Medical Discovery Institute
2021
University of New Haven
2018
Queen Margaret University
2009-2014
University of Wisconsin–Madison
1992-2014
University of Hertfordshire
2014
Aberdeen Maternity Hospital
2004
Oklahoma State University Center for Health Sciences
1992
Poultry CRC
1962
Nonalcoholic fatty liver disease (NAFLD) is becoming a leading cause of advanced chronic disease. The progression NAFLD, including nonalcoholic steatohepatitis (NASH), has strong genetic component, and the most robust contributor patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 encoding 148M protein sequence variant. We hypothesized that suppressing expression PNPLA3 mutant would exert beneficial effect on entire spectrum NAFLD. examined effects liver-targeted...
Spinal and bulbar muscular atrophy (SBMA) is caused by the polyglutamine androgen receptor (polyQ-AR), a protein expressed both lower motor neurons skeletal muscle. Although viewed as neuronopathy, data from patients mouse models suggest that muscle contributes to disease pathogenesis. Here, we tested this hypothesis using AR113Q knockin human bacterial artificial chromosome/clone (BAC) transgenic mice express full-length polyQ-AR display androgen-dependent weakness, atrophy, early death. We...
Abstract Enhancing the functional uptake of antisense oligonucleotide (ASO) in muscle will be beneficial for developing ASO therapeutics targeting genes expressed muscle. We hypothesized that improving albumin binding facilitate traversal from blood compartment to interstitium tissues enhance uptake. synthesized structurally diverse saturated and unsaturated fatty acid conjugated ASOs with a range hydrophobicity. The affinity conjugates plasma proteins improved chain length highest was...
Advances in the medicinal chemistry of antisense oligonucleotide drugs have been instrumental achieving and optimizing activity cell types other than hepatocytes, type that is most sensitive to effects following systemic treatment. To broadly characterize on target messenger RNA (mRNA) levels different organs animals, we developed a situ hybridization technique using noncoding metastasis associated lung adenocarcinoma transcript 1 (MALAT1) as surrogate target. We used this evaluate...
We determined the effect of attaching palmitate, tocopherol or cholesterol to PS ASOs and their effects on plasma protein binding enhancing ASO potency in muscle rodents monkeys. found that conjugates showed 5-fold enhancement relative unconjugated ASOs. However, they were toxic mice as a result not evaluated monkey. In contrast, palmitate tocopherol-conjugated enhanced skeletal modest enhancements Analysis plasma-protein profiles ASO-conjugates by size-exclusion chromatography revealed...
Abstract Aims Amyloidogenic transthyretin (ATTR) amyloidosis is a fatal disease characterized by progressive cardiomyopathy and/or polyneuropathy. AKCEA‐TTR‐L Rx (ION‐682884) ligand‐conjugated antisense drug designed for receptor‐mediated uptake hepatocytes, the primary source of circulating (TTR). Enhanced delivery pharmacophore expected to increase potency and support lower, less frequent dosing in treatment. Methods results demonstrated an approximate 50‐fold 30‐fold compared with...
Immune checkpoints (CTLA4 & PD-1) are inhibitory pathways that block aberrant immune activity and maintain self-tolerance. Tumors co-opt these to avoid destruction. checkpoint inhibitors (ICIs) activate cells restore their tumoricidal potential, making them highly efficacious cancer therapies. However, immunotolerant organs such as the liver depend on tolerogenic mechanisms, disruption with ICI use can trigger unintended side effect of hepatotoxicity termed immune-mediated injury from ICIs...
We report the evaluation of 20-, 18-, 16- and 14-mer phosphorothioate (PS)-modified tricycloDNA (tcDNA) gapmer antisense oligonucleotides (ASOs) in Tm, cell culture animal experiments compare them to their gap-matched 20-mer 2′-O-methoxyethyl (MOE) 2′,4′-constrained ethyl (cEt) counterparts. The sequence-matched tcDNA MOE ASOs showed similar Tm activity under free-uptake cationic lipid-mediated transfection conditions, while were moderate significantly less active. These observations...
Depletion of Chop in pancreatic β cells optimizes insulin secretion and reduces fatty liver preclinical models.
The purpose of this study was to assess the effect alternative ways providing information about risks twins on couples' perceptions elective single embryo transfer (eSET).Couples undergoing IVF were randomized into three groups. Group 1 received a standard pack, group 2 an extra leaflet twin pregnancy, and 3 additional discussion session. primary outcome measure acceptability hypothetical policy eSET. Data collected by means questionnaire.eSET acceptable 17 (27%), 20 (30%) 24 (32%) couples...
Abstract Emergent research indicates that electronic portfolios (ePortfolios) can have a positive impact on the learning experience, but there are significant challenges—pedagogical and technological—which may limit their effectiveness. This paper contributes to by providing further evidence about such challenges from tutor perspective offers suggestions how institutions address these issues. The draws upon 23 semi‐structured interviews conducted with tutors in range of subject areas,...
It has been suggested that binding of phosphorothioate oligodeoxynucleotides (P=S ODNs) to macrophage scavenger receptors (SR-AI/II) is the primary mechanism P=S ODN uptake into cells in vivo. To address role distribution vivo, several pharmacokinetic and pharmacological parameters were compared tissues from receptor knockout mice (SR-A-/-) their wild-type counterparts after i.v. administration 5- 20-mg/kg doses ODN. With an antibody recognizes ODN, no differences cellular or staining...
AGPAT2 (1-acyl-sn-glycerol-3-phosphate-acyltransferase-2) converts lysophosphatidic acid (LPA) into phosphatidic (PA), and mutations of the gene cause most common form congenital generalized lipodystrophy which leads to steatohepatitis. The underlying mechanism by deficiency steatohepatitis has not been elucidated. We addressed this question using an antisense oligonucleotide (ASO) knockdown expression Agpat2 in liver white adipose tissue (WAT) adult male Sprague-Dawley rats. ASO treatment...
High levels of student dissatisfaction and attrition persist in blended online distance learning programmes. As students tutors become more geographically dispersed with fewer opportunities for face-to-face contact emergent technologies like Online Synchronous Learning Environments (OSLEs) may provide an interactive, connected environment. OSLEs, such as Blackboard Collaborate Adobe Connect, are web-based, computer-mediated communication programs typically using video audio. This article...
AbstractBackground: Academic and pastoral support is fundamental to the achievement of a high-quality student learning experience.Aim: This study reports on full-time undergraduate students' views effectiveness academic in one higher education institution. The intent was explore how provided gain an appreciation value placed each method used.Method: 935 students from range subject disciplines responded Bristol-on-Line Survey questionnaire.Findings: Analysis quantitative data revealed that...