A5054150655- Endoplasmic Reticulum Stress and Disease
- Turtle Biology and Conservation
- Herpesvirus Infections and Treatments
- Phagocytosis and Immune Regulation
- Amphibian and Reptile Biology
- Bird parasitology and diseases
- Viral Infections and Vectors
- Animal Disease Management and Epidemiology
- Environmental DNA in Biodiversity Studies
- Rabies epidemiology and control
- Autophagy in Disease and Therapy
- Microbial infections and disease research
- Virology and Viral Diseases
- Identification and Quantification in Food
- Virus-based gene therapy research
- Species Distribution and Climate Change
- Poxvirus research and outbreaks
- Animal Virus Infections Studies
- Zoonotic diseases and public health
- Cell death mechanisms and regulation
- Polar Research and Ecology
- Atherosclerosis and Cardiovascular Diseases
- Microbial Community Ecology and Physiology
- Cryospheric studies and observations
- Photosynthetic Processes and Mechanisms
Wildlife Conservation Society
2016-2025
Columbia University Irving Medical Center
2009-2020
Wildlife Conservation Society United Kingdom
2012-2019
Columbia University
2006-2018
University of California, San Diego
2010
University of Massachusetts Chan Medical School
2009
University of British Columbia
2009
University of California, Los Angeles
2009
Brigham and Women's Hospital
2009
Harvard University
2008-2009
Two key features of atherosclerotic plaques that precipitate acute atherothrombotic vascular occlusion ("vulnerable plaques") are abundant inflammatory mediators and macrophages with excess unesterified, or "free," cholesterol (FC). Herein we show FC accumulation in leads to the induction secretion two cytokines, tumor necrosis factor-alpha (TNF-alpha) interleukin-6 (IL-6). The increases TNF-alpha IL-6 mRNA protein were mediated by FC-induced activation IkappaB kinase/NF-kappaB pathway as...
ER stress-induced apoptosis is implicated in various pathological conditions, but the mechanisms linking stress-mediated signaling to downstream apoptotic pathways remain unclear. Using human and mouse cell culture vivo models of apoptosis, we have shown that cytosolic calcium resulting from stress induces expression Fas death receptor through a pathway involving calcium/calmodulin-dependent protein kinase IIgamma (CaMKIIgamma) JNK. Remarkably, CaMKIIgamma was also responsible for processes...
Macrophage death in advanced atherosclerosis promotes necrosis and plaque destabilization. A likely cause of macrophage is accumulation free cholesterol (FC) the ER, leading to activation unfolded protein response (UPR) C/EBP homologous (CHOP)–induced apoptosis. Here we show that p38 MAPK signaling necessary for CHOP induction Additionally, two other pathways must cooperate with p38-CHOP effect One involves type scavenger receptor (SRA). As evidence, FC loading by non-SRA mechanisms...
Abstract The microbiome is essential for extraction of energy and nutrition from plant-based diets may have facilitated primate adaptation to new dietary niches in response rapid environmental shifts. Here we use 16S rRNA sequencing characterize the microbiota wild western lowland gorillas sympatric central chimpanzees demonstrate compositional divergence between microbiotas gorillas, chimpanzees, Old World monkeys, modern humans. We show that gorilla chimpanzee microbiomes fluctuate with...
The scavenger receptors SR-A and CD36 have been implicated in macrophage foam cell formation during atherogenesis the regulation of inflammatory signaling pathways, including those leading to lesional apoptosis plaque necrosis. To test impact deleting these receptors, we generated Apoe(-/-) mice lacking both fed them a Western diet for 12 weeks.We analyzed atheroma mice, assessing lesion size, formation, gene expression, apoptosis, necrotic core formation. Aortic root atherosclerosis...
Abstract High‐alpine life forms and ecosystems exist at the limits of habitable environments, thus, are especially sensitive to environmental change. Here we report a recent increase in elevational limit anurans following glacial retreat tropical Peruvian Andes. Three species have colonized ponds recently deglaciated terrain new record elevations for amphibians worldwide (5244–5400 m). Two these were also found be infected with Batrachochytrium dendrobatidis ( Bd ), an emerging fungal...
Rationale : Antiatherogenic effects of plasma high-density lipoprotein (HDL) include the ability to inhibit apoptosis macrophage foam cells. The ATP-binding cassette transporters ABCA1 and ABCG1 have a major role in promoting cholesterol efflux from macrophages apolipoprotein A-1 HDL are upregulated during phagocytosis apoptotic cells (efferocytosis). Objective goal this study was determine roles preserving viability efferocytosis. Methods Results We show that despite similar clearance...
The molecular events linking lipid accumulation in atherosclerotic plaques to complications such as aneurysm formation and plaque disruption are poorly understood. BALB/c- Apoe −/− mice bearing a null mutation the Npc1 gene display prominent medial erosion atherothrombosis, whereas their macrophages accumulate free cholesterol late endosomes show increased cathepsin K ( Ctsk ) expression. We now immunostaining cysteinyl proteinase activity using near infrared fluorescence imaging over...
Macrophage pattern recognition receptors (PRRs) play key roles in innate immunity, but they also may contribute to disease processes under certain pathological conditions. We recently showed that engagement of the type A scavenger receptor (SRA), a PRR, triggers JNK-dependent apoptosis endoplasmic reticulum (ER)-stressed macrophages. In advanced atherosclerotic lesions, SRA, activated JNK, and ER stress are observed macrophages, macrophage death atheromata leads plaque necrosis. Herein, we...
The global trade in wildlife has historically contributed to the emergence and spread of infectious diseases. United States is world's largest importer products, yet minimal pathogen surveillance precluded assessment health risks posed by this practice. This report details findings a pilot project establish methodology for zoonotic agents confiscated products. Initial from samples collected at several international airports identified parts originating nonhuman primate (NHP) rodent species,...
ER stress occurs in macrophage-rich areas of advanced atherosclerotic lesions and contributes to macrophage apoptosis subsequent plaque necrosis. Therefore, signaling pathways that alter stress–induced may affect atherosclerosis. Here we placed Apoe–/– mice deficient p38α MAPK on a Western diet found they had marked increase The p38α–deficient also exhibited significant reduction collagen content thinning the fibrous cap, which suggests progression was these mice. Consistent with our vivo...
Background The endoplasmic reticulum (ER) stress pathway known as the Unfolded Protein Response (UPR) is an adaptive survival that protects cells from buildup of misfolded proteins, but under certain circumstances it can lead to apoptosis. ER has been causally associated with macrophage apoptosis in advanced atherosclerosis mice and humans. Because shares features tuberculosis (TB) regard lesional accumulation, foam cell formation, apoptosis, we investigated if activated during TB infection....
Fewer than 500 Amur tigers (Panthera tigris altaica) remain in the wild. Due to low numbers and their solitary reclusive nature, tiger sightings across range Russian Far East China are rare; of sick rarer still. Serious neurologic disease observed several wild since 2001 suggested emergence this endangered species. To investigate possibility, histology, immunohistochemistry (IHC), situ hybridization (ISH), reverse transcription-PCR (RT-PCR) were performed on tissues from 5 affected that died...
Abstract Species monitoring using environmental DNA (eDNA) is a powerful new technique for natural resource scientists and the number of research groups employing eDNA detection growing rapidly. However, current sampling technologies consist mainly do‐it‐yourself solutions, lack purpose‐built equipment limiting efficiency standardization studies. Here, we describe first fully integrated system (Smith‐Root Sampler) designed by team molecular ecologists engineers high‐throughput sample...
Background— Macrophage apoptosis is a critical process in the formation of necrotic cores vulnerable atherosclerotic plaques. In vitro and vivo data suggest that macrophage advanced atheromata may be triggered by combination endoplasmic reticulum stress engagement type A scavenger receptor, which together induce death through rise cytosolic calcium activation toll-like receptor-4. Methods Results— Using both primary peritoneal macrophages studies vivo, we introduce signal transducer...
Plaque necrosis in advanced atheromata, which triggers acute atherothrombotic vascular events, is caused by the apoptosis of lesional macrophages coupled with defective phagocytic clearance dead cells. The central enabling event macrophage relevant to atherosclerosis unfolded protein response (UPR), an endoplasmic reticulum (ER) stress pathway. UPR effector CHOP (GADD153) amplifies release ER Ca(2+) stores, activates a integrator signaling, calcium/calmodulin-dependent kinase II (CaMKII)....
The ability to sequence a variety of wildlife samples with portable, field-friendly equipment will have significant impacts on conservation and health applications. However, the only currently available DNA sequencer, MinION by Oxford Nanopore Technologies, has high error rate compared standard laboratory-based sequencing platforms not been systematically validated for barcoding accuracy preserved non-invasively collected tissue samples. We tested whether various sample types, methods, our...
Canine distemper virus (CDV) has recently emerged as an extinction threat for the endangered Amur tiger (Panthera tigris altaica). CDV is vaccine-preventable, and control strategies could require vaccination of domestic dogs and/or wildlife populations. However, remains controversial, which led to a focus on interventions in dogs, often assumed be source infection. Effective decision making requires understanding true reservoir dynamics, poses substantial challenges remote areas with diverse...
Protein kinase Cδ (PKCδ) mediates apoptosis downstream of many apoptotic stimuli. Because its ubiquitous expression, tight regulation the proapoptotic function PKCδ is critical for cell survival. Full-length found in all cells, whereas catalytic fragment PKCδ, generated by caspase cleavage, only present cells undergoing apoptosis. Here we show that full-length transiently accumulates nucleus response to etoposide and nuclear translocation precedes cleavage PKCδ. Nuclear either cleaved 3,...
Endoplasmic reticulum stress increases macrophage apoptosis, contributing to the complications of atherosclerosis. Insulin-resistant macrophages are more susceptible endoplasmic stress-associated apoptosis probably death and necrotic core formation in atherosclerotic plaques type 2 diabetes. However, molecular mechanisms increased insulin-resistant remain unclear.The studies were performed isolated from insulin receptor knockout or ob/ob mice. Gain- loss-of-function approaches used evaluate...