A5017175650- Sirtuins and Resveratrol in Medicine
- Calcium signaling and nucleotide metabolism
- Cancer, Hypoxia, and Metabolism
- Biochemical and Molecular Research
- Adenosine and Purinergic Signaling
- PARP inhibition in cancer therapy
- Chemical Reactions and Isotopes
- RNA modifications and cancer
- Cognitive Abilities and Testing
- Early Childhood Education and Development
- Adipose Tissue and Metabolism
- Connexins and lens biology
- Autophagy in Disease and Therapy
- Photoreceptor and optogenetics research
- Advanced Breast Cancer Therapies
- Corneal Surgery and Treatments
- Circadian rhythm and melatonin
- Child and Animal Learning Development
- Cellular Mechanics and Interactions
- Educational and Psychological Assessments
- Ocular Surface and Contact Lens
- Cancer therapeutics and mechanisms
- Cancer Research and Treatments
- Bioactive natural compounds
- Nuclear Receptors and Signaling
Universidad de la República
2004-2024
Universidad de Montevideo
2007-2019
Mayo Clinic
2010-2016
WinnMed
2010-2016
Yale University
2015
UConn Health
2015
Mayo Clinic in Florida
2014
Mayo Clinic in Arizona
2014
Metabolic syndrome is a growing health problem worldwide. It therefore imperative to develop new strategies treat this pathology. In the past years, manipulation of NAD(+) metabolism has emerged as plausible strategy ameliorate metabolic syndrome. particular, an increase in cellular levels beneficial effects, likely because activation sirtuins. Previously, we reported that CD38 primary NAD(+)ase mammals. Moreover, knockout mice have higher and are protected against obesity Here, show...
The enzyme sirtuin 1 (SIRT1) is a critical regulator of many cellular functions, including energy metabolism. However, the precise mechanisms that modulate SIRT1 activity remain unknown. As in vitro was recently found to be negatively regulated by interaction with deleted breast cancer–1 (DBC1) protein, we set out investigate whether DBC1 regulates vivo. We and colocalized interacted, modulated activity, multiple cell lines tissues. In mouse liver, increased concomitant decreased DBC1-SIRT1...
Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the accumulation of cysts that ultimately leads to loss renal function and failure. At present, treatment for ADPKD largely supportive. Multiple studies have focused on pharmacologic approaches slow development cystic disease; however, little known about role nutrition dietary manipulation in PKD. Here, we show food restriction (FR) effectively slows course mouse models ADPKD. Mild moderate (10%-40%)...
Abstract Purpose: Here, we describe a novel interplay between NAD synthesis and degradation involved in pancreatic tumor growth. Experimental Design: We used human cancer cells, both vitro (cell culture experiments) vivo (xenograft experiments), to demonstrate the role of cell metabolism Results: demonstrated that pharmacologic genetic targeting Nampt, key enzyme salvage pathway, inhibits growth survival cells. These changes were accompanied by reduction levels, glycolytic flux, lactate...
The NAD(+)-dependent deacetylase SIRT1 is a key regulator of several aspects metabolism and aging. activation beneficial for human diseases, including metabolic syndrome, diabetes, obesity, liver steatosis, Alzheimer disease. We have recently shown that the protein deleted in breast cancer 1 (DBC1) activity vivo. Furthermore, DBC1 form dynamic complex regulated by energetic state organism. Understanding how interaction between therefore essential to design strategies aimed activate SIRT1....
HDAC3 is a member of the class I histone deacetylase family that regulates gene expression by deacetylation histones and non-histone proteins. activity has been shown to be modulated interaction with co-repressors NCoR SMRT. Here, we present evidence nuclear protein DBC1 an endogenous inhibitor HDAC3. previously identified as regulator some receptors, methyltransferase SUV39H1, NAD-dependent SIRT1. Furthermore, influence transcription regulation apoptosis, it may also act tumor suppressor....
The Intracellular levels of nicotinamide adenine dinucleotide (NAD+) are rhythmic and controlled by the circadian clock. However, whether NAD+ oscillation in turn contributes to physiology is not fully understood. To address this question we analyzed mice mutated for hydrolase CD38. We found that rhythmicity was altered CD38-deficient mice. high, chronic results several anomalies behavior metabolism. CD38-null display a shortened period length locomotor activity alteration rest-activity...
Objective— Neuropilin-1 (NRP-1) is a multidomain membrane receptor involved in angiogenesis and development of neuronal circuits, however, the role NRP-1 cardiovascular pathophysiology remains elusive. Approach Results— In this study, we first observed that deletion induced peroxisome proliferator–activated γ coactivator 1α cardiomyocytes vascular smooth muscle cells, which was accompanied by dysregulated cardiac mitochondrial accumulation induction hypertrophy- stress-related markers. To...
Abstract Purpose: Recent studies suggest that SIRT1-activating compounds (STAC) are a promising class of anticancer drugs, although their mechanism action remains elusive. The main goal this study is to determine the role STACs as potential therapy for pancreatic cancer. In addition, we also explored by which these affect Experimental design: Using in vitro (cell culture experiments) and vivo (xenograft approaches, studied SIRT1 agonists human cancer cell viability growth. Results: We show...
The nuclear receptor Rev-erbα has been implicated as a major regulator of the circadian clock and integrates rhythm metabolism. controls oscillations several genes protein degradation is important for maintenance also adipocyte differentiation. Elucidating mechanisms that regulate stability essential our understanding these processes. In present paper, we report DBC1 (Deleted in Breast Cancer 1) novel Rev-erbα. interact cells vivo, modulates repressor function. Depletion by siRNA (small...
Abstract Immediately after wounding, bovine corneal endothelial cells develop a fast calcium wave that propagates from the wound border to rest of monolayer and extinguishes in approximately 5 minutes. One hour late, slow ( SCW ) develops concomitantly depolarization plasma membrane potential cells. The incorporation inhibitors epithelial sodium channel sodium‐calcium exchanger produces inhibition , diminishes rate healing. L‐type blocker nimodipine does not have any effect on . reversible...
Chronic obesity leads to inflammation, tissue dysfunction, and cellular senescence. It was proposed that senescence during aging drives inflammation dysfunction. Consistent with this, clearance of senescent cells increases healthspan in progeroid mice. Here, we show the protein Deleted Breast Cancer-1 (DBC1) regulates obesity. Deletion DBC1 protects preadipocytes against senescence-driven inflammation. Furthermore, protection KO mice Finally, found participates onset response cell damage by...
Mate Marote is an open-access cognitive training software aimed at children between 4 and 8 years old. It consists of a set computerized games specifically tailored to train evaluate Executive Functions (EF), class processes critical for purposeful, goal-directed behavior, including working memory, planning, flexibility, inhibitory control. Since 2008, several studies were performed with this children’s own schools in interventions supervised in-person by scientists. After 2015, we...
Abstract In previous works we showed that the depolarization of plasma membrane potential (PMP) determines a reorganization cytoskeleton diverse epithelia in culture, consisting mainly reallocation peripheral actin toward cell center, ultimately provoking intercellular disruption. view this evidence, explored study possible effects hyperpolarization on cytoskeletal organization and adherens junction (AJ) morphology stability confluent bovine corneal endothelial cells culture. For purpose,...
Abstract Executive functions (EF), either conceptualized as skills involved in regulation of cognition and emotion service goal‐oriented behavior, or reductively working memory, flexibility inhibitory control, are commonly invoked constructs developmental science. Two main traditions on EFs measurement prevail, one consisting ratings obtained through questionnaires that inquire behavior common situations, the other based performance laboratory tasks. Whether both types assessment actually...
Obesity is often regarded as the primary cause of metabolic syndrome. However, many lines evidence suggest that obesity may develop a protective mechanism against tissue damage during caloric surplus and it only when maximum fat accumulation capacity reached fatty acid spillover occurs into to peripheral tissues diseases develop. In this regard, identifying molecular mechanisms modulate adipocyte imperative. Here we identify deleted in breast cancer 1 (DBC1) protein key regulator storage...
CD38 is an ecto-enzyme that hydrolyzes NAD. Its expression a prognostic marker for chronic lymphocytic leukemia. We have characterized individual variation in lymphoblastoid cell lines from 288 healthy subjects of three ethnicities. Expression varied widely, with significant differences among ethnic groups, and was correlated significantly enzymatic activity protein levels. The gene then resequenced using DNA the same lines, identification 53 single nucleotide polymorphisms (SNPs) one indel,...
Future-oriented decision-making is an important adaptive behavior. In the present study, we examined whether varies as a function of socioeconomic status (SES) using Children's Gambling task (CGT). We administered CGT to 227 children (49% female, 48% low SES) between ages 5 and 7 years. After completing CGT, assessed children's knowledge reward/loss contingencies. Data analysis was conducted through multilevel modeling. Fluid intelligence, measured by Test Nonverbal Intelligence, included...
Early childhood is a period characterized by the rapid development of several cognitive abilities known as executive functions (EFs), required for all kinds learning and adaptive behavior. Like other aspects development, both positive detrimental environmental conditions can have potential impact on EF maturation. For instance, an improvement in usually reported when children engage activities that gradually systematically challenge them. Mate Marote free online platform with videogames...
In the article listed above, there are errors in Figures 3, 4, and 5, which show effects of quercetin apigenin …