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Full-Text Articles in Medicine and Health Sciences
Crispr-Cas9 Mediated Epitope Tagging Provides Accurate And Versatile Assessment Of Myocardin--Brief Report, Qing Lyu, Vidhi Dhagia, Yu Han, Bing Guo, Mary E. Wines-Samuelson, Christine K. Christie, Qiangzong Yin, Orazio J. Slivano, Paul Herring, Xiaochun Long, Sachin A. Gupte, Joseph M. Miano
Crispr-Cas9 Mediated Epitope Tagging Provides Accurate And Versatile Assessment Of Myocardin--Brief Report, Qing Lyu, Vidhi Dhagia, Yu Han, Bing Guo, Mary E. Wines-Samuelson, Christine K. Christie, Qiangzong Yin, Orazio J. Slivano, Paul Herring, Xiaochun Long, Sachin A. Gupte, Joseph M. Miano
NYMC Faculty Publications
OBJECTIVE: Unreliable antibodies often hinder the accurate detection of an endogenous protein, and this is particularly true for the cardiac and smooth muscle cofactor, MYOCD (myocardin). Accordingly, the mouse Myocd locus was targeted with 2 independent epitope tags for the unambiguous expression, localization, and activity of MYOCD protein. APPROACH AND RESULTS: 3cCRISPR (3-component clustered regularly interspaced short palindromic repeat) was used to engineer a carboxyl-terminal 3xFLAG or 3xHA epitope tag in mouse embryos. Western blotting with antibodies to each tag revealed a protein product of approximately 150 kDa, a size considerably larger than that reported in virtually all publications. MYOCD …
Sleeper Cells: The Stringent Response And Persistence In The Borreliella (Borrelia) Burgdorferi Enzootic Cycle, Felipe C. Cabello, Henry Godfrey, J Bugrysheva, Stuart A. Newman
Sleeper Cells: The Stringent Response And Persistence In The Borreliella (Borrelia) Burgdorferi Enzootic Cycle, Felipe C. Cabello, Henry Godfrey, J Bugrysheva, Stuart A. Newman
NYMC Faculty Publications
Infections with tick-transmitted Borreliella (Borrelia) burgdorferi, the cause of Lyme disease, represent an increasingly large public health problem in North America and Europe. The ability of these spirochetes to maintain themselves for extended periods of time in their tick vectors and vertebrate reservoirs is crucial for continuance of the enzootic cycle as well as for the increasing exposure of humans to them. The stringent response mediated by the alarmone (p)ppGpp has been determined to be a master regulator in B. burgdorferi. It modulates the expression of identified and unidentified open reading frames needed to deal with and overcome the many …
Nlrp9b Inflammasome Restricts Rotavirus Infection In Intestinal Epithelial Cells, Shu Zhu, Siyuan Ding, Penghua Wang, Zheng Wei, Wen Pan, Noah Palm, Richard Flavell
Nlrp9b Inflammasome Restricts Rotavirus Infection In Intestinal Epithelial Cells, Shu Zhu, Siyuan Ding, Penghua Wang, Zheng Wei, Wen Pan, Noah Palm, Richard Flavell
NYMC Faculty Publications
Rotavirus, a leading cause of severe gastroenteritis and diarrhoea in young children, accounts for around 215,000 deaths annually worldwide. Rotavirus specifically infects the intestinal epithelial cells in the host small intestine and has evolved strategies to antagonize interferon and NF-κB signalling, raising the question as to whether other host factors participate in antiviral responses in intestinal mucosa. The mechanism by which enteric viruses are sensed and restricted in vivo, especially by NOD-like receptor (NLR) inflammasomes, is largely unknown. Here we uncover and mechanistically characterize the NLR Nlrp9b that is specifically expressed in intestinal epithelial cells and restricts rotavirus infection. Our …
Coprinus Comatus Cap Inhibits Adipocyte Differentiation Via Regulation Of Pparγ And Akt Signaling Pathway, Hyoung Joon Park, Jisoo Yun, Hong-Duck Kim, Chung-Kil Won, Gon-Sup Kim, Jae-Hyeon Cho
Coprinus Comatus Cap Inhibits Adipocyte Differentiation Via Regulation Of Pparγ And Akt Signaling Pathway, Hyoung Joon Park, Jisoo Yun, Hong-Duck Kim, Chung-Kil Won, Gon-Sup Kim, Jae-Hyeon Cho
NYMC Faculty Publications
This study assessed the effects of Coprinus comatus cap (CCC) on adipogenesis in 3T3-L1 adipocytes and the effects of CCC on the development of diet-induced obesity in rats. Here, we showed that the CCC has an inhibitory effect on the adipocyte differentiation of 3T3-L1 cells, resulting in a significant decrease in lipid accumulation through the downregulation of several adipocyte specific-transcription factors, including CCAAT/enhancer binding protein β, C/EBPδ, and peroxisome proliferator-activated receptor gamma (PPARγ). Moreover, treatment with CCC during adipocyte differentiation induced a significant down-regulation of PPARγ and adipogenic target genes, including adipocyte protein 2, lipoprotein lipase, and adiponectin. Interestingly, the …
Tlr4 Mutation Reduces Microglial Activation, Increases Aβ Deposits And Exacerbates Cognitive Deficits In A Mouse Model Of Alzheimer's Disease, Min Song, Jingji Jin, Jinghong Kou, Abhinandan Pattanayak, Jamaal Rehman, Hong-Duck Kim, Ken-Ichiro Fukuchi
Tlr4 Mutation Reduces Microglial Activation, Increases Aβ Deposits And Exacerbates Cognitive Deficits In A Mouse Model Of Alzheimer's Disease, Min Song, Jingji Jin, Jinghong Kou, Abhinandan Pattanayak, Jamaal Rehman, Hong-Duck Kim, Ken-Ichiro Fukuchi
NYMC Faculty Publications
BACKGROUND: Amyloid plaques, a pathological hallmark of Alzheimer's disease (AD), are accompanied by activated microglia. The role of activated microglia in the pathogenesis of AD remains controversial: either clearing Aβ deposits by phagocytosis or releasing proinflammatory cytokines and cytotoxic substances. Microglia can be activated via toll-like receptors (TLRs), a class of pattern-recognition receptors in the innate immune system. We previously demonstrated that an AD mouse model homozygous for a loss-of-function mutation of TLR4 had increases in Aβ deposits and buffer-soluble Aβ in the brain as compared with a TLR4 wild-type AD mouse model at 14-16 months of age. However, it …
Simvastatin Enhances Immune Responses To Aβ Vaccination And Attenuates Vaccination-Induced Behavioral Alterations, Jinghong Kou, Hong-Duck Kim, Jingji Jin, Dongfeng Cao, Ling Li, Robert Lalonde, Ken-Ichiro Fukuchi
Simvastatin Enhances Immune Responses To Aβ Vaccination And Attenuates Vaccination-Induced Behavioral Alterations, Jinghong Kou, Hong-Duck Kim, Jingji Jin, Dongfeng Cao, Ling Li, Robert Lalonde, Ken-Ichiro Fukuchi
NYMC Faculty Publications
Statins are widely used to lower cholesterol levels by inhibiting cholesterol biosynthesis. Some evidence has indicated that statins might have therapeutic and preventive benefits for Alzheimer's disease (AD). We and others also have shown the beneficial effect of statin treatment in reversing learning and memory deficits in animal models of AD. However, data from clinical trials are inconclusive. We previously documented that the adenovirus vector encoding 11 tandem repeats of Aβ1-6 fused to the receptor-binding domain (Ia) of Pseudomonas exotoxin A, AdPEDI-(Aβ1-6)(11), is effective in inducing an immune response against amyloid-β protein (Aβ) and reducing brain Aβ load in Alzheimer's …
Atf4 Is An Oxidative Stress–Inducible, Prodeath Transcription Factor In Neurons In Vitro And In Vivo, Philipp Lange, Juan Chavez, John T. Pinto, Giovanni Coppola, Chiao-Wang Sun, Tim Townes, Rajiv Ratan
Atf4 Is An Oxidative Stress–Inducible, Prodeath Transcription Factor In Neurons In Vitro And In Vivo, Philipp Lange, Juan Chavez, John T. Pinto, Giovanni Coppola, Chiao-Wang Sun, Tim Townes, Rajiv Ratan
NYMC Faculty Publications
Oxidative stress is pathogenic in neurological diseases, including stroke. The identity of oxidative stress-inducible transcription factors and their role in propagating the death cascade are not well known. In an in vitro model of oxidative stress, the expression of the bZip transcription factor activating transcription factor 4 (ATF4) was induced by glutathione depletion and localized to the promoter of a putative death gene in neurons. Germline deletion of ATF4 resulted in a profound reduction in oxidative stress-induced gene expression and resistance to oxidative death. In neurons, ATF4 modulates an early, upstream event in the death pathway, as resistance to oxidative …
Impaired Fast-Spiking, Suppressed Cortical Inhibition, And Increased Susceptibility To Seizures In Mice Lacking Kv3.2 K+ Channel Proteins, David Lau, Eleazar Vega-Saenz De Miera, Diego Contreras, Alan Chow, Richard Paylor, Christopher S. Leonard, Bernardo Rudy
Impaired Fast-Spiking, Suppressed Cortical Inhibition, And Increased Susceptibility To Seizures In Mice Lacking Kv3.2 K+ Channel Proteins, David Lau, Eleazar Vega-Saenz De Miera, Diego Contreras, Alan Chow, Richard Paylor, Christopher S. Leonard, Bernardo Rudy
NYMC Faculty Publications
Voltage-gated K(+) channels of the Kv3 subfamily have unusual electrophysiological properties, including activation at very depolarized voltages (positive to -10 mV) and very fast deactivation rates, suggesting special roles in neuronal excitability. In the brain, Kv3 channels are prominently expressed in select neuronal populations, which include fast-spiking (FS) GABAergic interneurons of the neocortex, hippocampus, and caudate, as well as other high-frequency firing neurons. Although evidence points to a key role in high-frequency firing, a definitive understanding of the function of these channels has been hampered by a lack of selective pharmacological tools. We therefore generated mouse lines in which one …