A5076644192- Pluripotent Stem Cells Research
- Menopause: Health Impacts and Treatments
- Mitochondrial Function and Pathology
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Neurological Disease Mechanisms and Treatments
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Reproductive Biology and Fertility
- Regulation of Appetite and Obesity
- Nuclear Structure and Function
- Stress Responses and Cortisol
- Adipose Tissue and Metabolism
- Tryptophan and brain disorders
- Alzheimer's disease research and treatments
- Diverse Educational Innovations Studies
- Genomics and Chromatin Dynamics
- Adipokines, Inflammation, and Metabolic Diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- DNA Repair Mechanisms
- RNA Interference and Gene Delivery
- European and International Law Studies
- Estrogen and related hormone effects
- Hemophilia Treatment and Research
Albany Medical Center Hospital
2021-2025
University of Birmingham
2019-2024
University of Leicester
2013-2024
Albert Einstein College of Medicine
2024
University at Albany, State University of New York
1968-2023
Memorial University of Newfoundland
2017-2019
Monash University
2010-2015
Hudson Institute of Medical Research
2015
BD Technologie (United States)
2015
Monash Institute of Medical Research
2010-2013
Approximately 70% of Alzheimer's disease (AD) patients have co-morbid vascular contributions to cognitive impairment and dementia (VCID); this highly prevalent overlap subtypes is known as mixed (MxD). AD more in women, while VCID slightly men. Sex differences risk factors may contribute sex subtypes. Unlike metabolically healthy diabetic women are likely develop than Prediabetes 3× diabetes linked earlier onset but not How prediabetes influences underlying pathology outcomes across...
DNA methylation is an essential mechanism controlling gene expression during differentiation and development. We investigated the epigenetic regulation of nuclear-encoded, mitochondrial (mtDNA) polymerase γ catalytic subunit ( PolgA ) by examining status a CpG island within exon 2 PolgA. Bisulphite sequencing identified low levels (<10%) mouse oocytes, blastocysts embryonic stem cells (ESCs), while somatic tissues contained significantly higher (>40%). In contrast, induced pluripotent (iPS)...
Significance Histone deacetylase 1 and 2 (HDAC1/2) are sister proteins that regulate access to DNA by modulating chromatin. We have generated the first double knockout (DKO) of Hdac1/2 in embryonic stem (ES) cells find gene inactivation causes a loss cell viability, which is associated with increased abnormal mitotic spindles chromosome segregation defects. Transcriptome analysis revealed almost 2,000 genes deregulated DKO cells. Significantly for self-renewal properties ES cells, this...
As stem cells undergo differentiation, mitochondrial DNA (mtDNA) copy number is strictly regulated in order that specialized can generate appropriate levels of adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS) to undertake their specific functions. It not understood whether tumor-initiating regulate mtDNA a similar manner or essential for tumorigenesis. We show human neural (hNSCs) increased content during differentiation process was mediated by synergistic relationship...
Stalled replication forks can be restarted and repaired by RAD51-mediated homologous recombination (HR), but HR also perform post-replicative repair after bypass of the obstacle. Bulky DNA adducts are important replication-blocking lesions, it is unknown whether they activate at stalled or behind ongoing forks. Using mainly BPDE-DNA as model we show that induced bulky in mammalian cells predominantly occurs gaps formed DNA/RNA primase PrimPol. RAD51 recruitment under these conditions does...
Abstract Background The vast majority of women with dementia are post-menopausal. Despite clinical relevance, menopause is underrepresented in rodent models dementia. Before menopause, less likely than men to experience strokes, obesity, and diabetes—known risk factors for vascular contributions cognitive impairment (VCID). During ovarian estrogen production stops the developing these spikes. Here, we aimed determine if worsens VCID. We hypothesized that would cause metabolic dysfunction...
Histone acetylation is a dynamic modification regulated by the opposing actions of histone acetyltransferases (HATs) and deacetylases (HDACs). Deacetylation tails results in chromatin tightening, therefore, HDACs are generally regarded as transcriptional repressors. Counterintuitively, simultaneous deletion Hdac1 Hdac2 embryonic stem cells (ESCs) reduces expression pluripotency-associated transcription factors Pou5f1 , Sox2 Nanog (PSN). By shaping global patterns, indirectly regulate...
Mitochondrial DNA haplotypes are associated with various phenotypes, such as altered susceptibility to disease, environmental adaptations, and aging. Accumulating evidence suggests that mitochondrial is essential for cell differentiation the phenotype. However, effects of different on development remain be determined. Using embryonic stem lines possessing same Mus musculus chromosomes but harboring one musculus, spretus, or terricolor haplotypes, we have determined chromosomal gene...
Menopause is an endocrine shift leading to increased vulnerability for cognitive impairment and dementia risk factors, in part due loss of neuroprotective circulating estrogens. Systemic replacement estrogen post-menopause has limitations, including estrogen-sensitive cancers. A promising therapeutic approach therefore might be deliver only the brain. We examined whether we could enhance performance by delivering exclusively brain ovariectomized mice (a surgical menopause model). treated...
Abstract INTRODUCTION Post‐menopausal women constitute about two‐thirds of those with Alzheimer's disease (AD). Menopause increases dementia risk by heightening the likelihood metabolic disease, a well‐known factor for dementia. We aimed to determine effects menopause and high‐fat diet (HF) on cognitive pathological outcomes in an AD mouse model. METHODS At 3 months old, App NL‐F mice received 4‐vinylcyclohexene diepoxide (menopause model) or vehicle were placed control (10% fat) HF (60%...
Interspecies somatic cell nuclear transfer (iSCNT) involves the of a nucleus or from one species into cytoplasm an enucleated oocyte another. Once activated, reconstructed oocytes can be cultured in vitro to blastocyst, final stage preimplantation development. However, they often arrest during early stages development; fail reprogramme nucleus; and eliminate accompanying donor cell's mitochondrial DNA (mtDNA) favour recipient oocyte's genetically more divergent population. This last point...
Abstract Background Damage to the cerebral vasculature can lead vascular contributions cognitive impairment and dementia (VCID). A reduction in blood flow brain leads neuropathology, including neuroinflammation white matter lesions that are a hallmark of VCID. Mid-life metabolic disease (obesity, prediabetes, or diabetes) is risk factor for VCID which may be sex-dependent (female bias). Methods We compared effects mid-life between males females chronic hypoperfusion mouse model C57BL/6J mice...
Abstract Background Alzheimer’s disease (AD) is notably associated with cognitive decline resulting from impaired function of hippocampal and cortical areas; however, several other domains corresponding brain regions are affected. One such region the hypothalamus, shown to atrophy develop amyloid tau pathology in AD patients. The hypothalamus controls functions necessary for survival, including energy glucose homeostasis. Changes appetite body weight common AD, often seen years prior onset...
Background Endothelial progenitor cells (EPCs) are implicated in a range of pathological conditions, suggesting natural therapeutic role for EPCs angiogenesis. However, current angiogenic therapies involving EPC transplantation inefficient due to rejection donor EPCs. One solution is derive an expanded population from stem vitro, be re-introduced as transplant. To demonstrate the potential we performed vitrotransplantation into endothelial cell (EC) tubules using gel-based tubule formation...
Real-time strategy games have become an increasingly popular test bed for modern artificial intelligence (AI) techniques. With this rise in popularity has come the creation of several annual competitions, which AI agents (bots) play full game StarCraft: Broodwar by Blizzard Entertainment. The three major StarCraft Competitions are Student Tournament, Computational Intelligence Games competition, and Artificial Interactive Digital Entertainment competition. In paper, we will give overview...
Oocyte cryopreservation is extremely beneficial for assisted reproductive technologies, the treatment of infertility and biotechnology offers a viable alternative to embryo freezing ovarian grafting approaches generation embryonic stem cells live offspring. It also potential store oocytes rescue endangered species by somatic cell nuclear transfer study development in these species. We vitrified mouse using range concentrations trehalose (0 0.3 M) demonstrated that 0.1 M had similar...
About two-thirds of those with Alzheimer's disease (AD) are women, most whom post-menopausal. Menopause accelerates dementia risk by increasing the for metabolic, cardiovascular, and cerebrovascular diseases. Mid-life metabolic (obesity, diabetes/prediabetes) is a well-known factor dementia. A high fat diet can lead to poor health in both humans rodents.
Menopause accelerates metabolic dysfunction, including (pre-)diabetes, obesity and visceral adiposity. However, the effects of endocrine vs. chronological aging in this progression are poorly understood. We hypothesize that menopause, especially context middle-age, will exacerbate a high fat diet. Using young-adult middle-aged C57BL/6J female mice, we modeled diet-induce via chronic administration (HF) diet control peri-menopause/menopause injections 4-vinylcyclohexene diepoxide, which...