A5076454979- Pancreatic function and diabetes
- Metabolism, Diabetes, and Cancer
- Diabetes Treatment and Management
- Microstructure and mechanical properties
- Aluminum Alloy Microstructure Properties
- Neonatal Respiratory Health Research
- Nuclear Structure and Function
- Aluminum Alloys Composites Properties
- RNA Research and Splicing
- Infant Nutrition and Health
- Pharmacological Effects and Toxicity Studies
- Receptor Mechanisms and Signaling
- Grief, Bereavement, and Mental Health
- Neonatal and Maternal Infections
- Microstructure and Mechanical Properties of Steels
- Adipose Tissue and Metabolism
- Iron Metabolism and Disorders
- Neonatal Health and Biochemistry
- Metabolism and Genetic Disorders
- Hemoglobinopathies and Related Disorders
- Birth, Development, and Health
- Child and Adolescent Health
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Nuclear Physics and Applications
- Healthcare Policy and Management
Marquette University
2024
Instituto Superior Politécnico Metropolitano de Angola
2024
Amgen (United States)
2012-2022
University of Pretoria
2018
Genomics Institute of the Novartis Research Foundation
2005-2014
Aberdeen Maternity Hospital
1980-2011
NHS Grampian
2009
University of Aberdeen
1981-2007
Royal Aberdeen Children's Hospital
1981-2007
Technology Centre Prague
2006-2007
Fibroblast growth factor 21 (FGF21) has emerged as an important metabolic regulator of glucose and lipid metabolism. The aims the current study are to evaluate role FGF21 in energy metabolism provide mechanistic insights into its lipid-lowering effects a high-fat diet-induced obesity (DIO) model.DIO or normal lean mice were treated with vehicle recombinant murine FGF21. Metabolic parameters including body weight, glucose, levels monitored, hepatic gene expression was analyzed. Energy insulin...
Nuclear migration and positioning within cells are critical for many developmental processes governed by the cytoskeletal network. Although mechanisms of nuclear-cytoskeletal attachment unclear, growing evidence links a novel family nuclear envelope (NE) proteins that share conserved C-terminal SUN (Sad1/UNC-84 homology) domain. Analysis Caenorhabditis elegans mutants has implicated UNC-84 in actin-mediated regulating NE anchoring giant actin-binding protein, ANC-1. Here, we report...
Glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) has been identified in multiple genome-wide association studies (GWAS) as a contributor to obesity, and GIPR knockout mice are protected against diet-induced obesity (DIO). On the basis of this genetic evidence, we developed anti-GIPR antagonistic antibodies potential therapeutic strategy for treatment observed that mouse anti-murine antibody (muGIPR-Ab) body weight gain, improved metabolic parameters, was associated with...
The gene encoding nuclear lamins A and C is mutated in at least three inherited disorders. Two of these, Emery–Dreifuss muscular dystrophy (EDMD-AD) a form dilated cardiomyopathy (CMD1A), involve muscle defects, the other, familial partial lipodystrophy (FPLD), involves loss subcutaneous adipose tissue. Mutations causing FPLD, contrast to those disorders, are tightly clustered within C-terminal domain lamin A/C. We investigated expression subcellular localization FPLD mutants found no...
Summary. It has been common practice in the United Kingdom for more than 30 years to classify perinatal deaths according maternal condition that initiated events led death. However, such an approach tends ignore baby as individual his or her own right. The need additional classification identifies pathological processes occurring every death long recognized, and adopted 1958 British Perinatal Mortality Survey now revised with this mind.
Abstract Mutations of the human B-RAF gene are detected in ∼8% cancer samples, primarily cutaneous melanomas (70%). The most common mutation (90%) is a valine-to-glutamic acid at residue 600 (V600E; formerly V599E according to previous nomenclature). Using Cre/Lox approach, we have generated conditional knock-in allele V600EB-raf mice. We show that widespread expression V600EB-Raf cannot be tolerated embryonic development, with embryos dying ∼7.5 dpc. Directed mutant somatic tissues using...
Insulin resistance develops in tandem with obesity. Ablating myostatin (Mstn) prevents obesity, so we investigated if Mstn deficiency could improve insulin sensitivity. A loss-of-function mutation (Mstn(Ln)) either one or both alleles of the gene shows how protects whole-body sensitivity.Mstn(Ln/Ln) mice were weaned onto a high-fat diet (HFD) standard diet. HFD-fed Mstn(Ln/Ln) exhibited high lean, low-fat body compositions compared wild types. Wild-type and heterozygous homozygous mutant...
Fibroblast growth factor 21 (FGF21) is a potent metabolic regulator, and pharmacological administration elicits glucose lipid lowering responses in mammals. To delineate if adipose tissue the predominant organ responsible for anti-diabetic effects of FGF21, we treated mice with reduced body fat (lipodystrophy specific expression active sterol regulatory element binding protein 1c; Tg) recombinant murine FGF21 (rmuFGF21). Unlike wildtype (WT) mice, Tg were refractory to beneficial rmuFGF21 on...
Abstract Antagonism or agonism of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) prevents weight gain and leads to dramatic loss in combination with glucagon-like peptide-1 agonists preclinical models. Based on genetic evidence supporting GIPR antagonism, we previously developed a mouse anti-murine antibody (muGIPR-Ab) that protected diet-induced obese (DIO) mice against body improved multiple metabolic parameters. This work reconciles similar effects antagonists...
Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) regulate glucose energy homeostasis. Targeting both pathways with GIP receptor (GIPR) antagonist antibody (GIPR-Ab) GLP-1 (GLP-1R) agonist, by generating GIPR-Ab/GLP-1 bispecific molecules, is an approach for treating obesity its comorbidities. In mice monkeys, these molecules reduce body weight (BW) improve many metabolic parameters. BW loss greater than GIPR-Ab or a control conjugate, suggesting...
Missense mutations of the lamin A/C gene, LMNA, have been recently identified in Dunnigan-type familial partial lipodystrophy (FPLD), which belongs to a heterogeneous group rare disorders affecting adipose tissue distribution and metabolism. In this study, we sequenced LMNA coding region from patients presenting with FPLD or other forms lipodystrophy. We two heterozygous exon 8, R482W R482Q, (six families one individual) various clinical presentations. addition, found novel mutation (R584H)...
A protein free artificial surfactant (artificial lung expanding compound; ALEC) composed of dipalmitoylphosphatidylcholine and phosphatidylglycerol was assessed for its effect on the main complications prematurity in a prospective two stage randomised trial 328 unselected babies delivered at between 25 29 weeks gestation. Babies were to receive approximately 100 mg suspension or 1 ml saline. This given birth into pharynx with up three more endotracheal doses if baby intubated during first...
Prohormone convertase 1 (PC1) mutations lead to obesity in humans. However, Pc1 knockout mice do not become obese; fact, they are runted due a defect growth-hormone releasing hormone processing, leading the speculation that PC1 subserves different functions between mouse and human. Here, we report novel allele of (N222D) leads obesity, abnormal proinsulin processing multiple endocrinological defects. Increased energy intake more efficient metabolism contribute Pc1(N222D/N222D) mice....
In a screen for genes that affect the metabolic response to high-fat diet (HFD), we selected one line of N-ethyl-N-nitrosourea (ENU)-mutagenized mice, Jll, with dominantly inherited resistance diet-induced obesity (DIO). Mutant animals had dramatically reduced body weight and fat mass, low basal insulin glucose levels relative unaffected controls. Both white adipose tissue (WAT) brown (BAT) depots were smaller in mutant animals. fed HFD gained only slightly more than regular chow, protected...
Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD), with more than 5.5% fat content, is a leading risk factor for chronic an estimated worldwide prevalence of 30%. Though MASLD widely recognized to be polygenic, genetic discovery has been lacking primarily due the need accurate and scalable phenotyping, which proves costly, time-intensive variable in quality. Here, we used machine learning (ML) predict content using three different data modalities available UK Biobank:...
Congenital nephrogenic diabetes insipidus (NDI) is a disease characterized by failure of the kidney to concentrate urine in response vasopressin. Human kindreds with have been found harbor mutations vasopressin receptor 2 (Avpr2) gene or vasopressin-sensitive water channel aquaporin-2 (Aqp2) gene. Development treatment rendered difficult due lack viable animal model. Through forward genetic screening ethylnitrosourea-mutagenized mice, we report identification and characterization mouse model...
A family is described in which 2 siblings born to healthy parents presented with abnormal facies, persistent diarrhoea, and early death. Exhaustive pathological biochemical investigations failed find a cause. The scalp hair of both babies had an amino-acid composition, appearance that was unique on scanning electron microscopical examination; this fact the clinical picture probably represents new syndrome.
OBJECTIVE Type 2 diabetes is caused by both environmental and genetic factors. To better understand the factors we used forward genetics to discover genes that have not previously been implicated in development of hyperglycemia or diabetes. RESEARCH DESIGN AND METHODS Offspring ethylnitrosurea-mutagenized C57BL/6 mice were bred homozygosity, maintained on high-fat diet, screened for hyperglycemia. The phenotype one diabetic family was mapped among hybrid F2s with single nucleotide...
We have recently reported a novel approach to increase cytosolic glucokinase (GK) levels through the binding of small molecule its endogenous inhibitor, regulatory protein (GKRP). These initial investigations culminated in identification 2-(4-((2S)-4-((6-amino-3-pyridinyl)sulfonyl)-2-(1-propyn-1-yl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (1, AMG-3969), compound that effectively enhanced GK translocation and reduced blood glucose diabetic animals. Herein we report results our...