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61.
A population of multipotent stem cells capable of differentiating into neurons and glia has been isolated from adult intestine in humans and rodents. While these cells may provide a pool of stem cells for neurogenesis in the enteric nervous system (ENS), such a function has been difficult to demonstrate in vivo. An extensive study by Joseph et al. involving 108 rats and 51 mice submitted to various insults demonstrated neuronal uptake of thymidine analog BrdU in only 1 rat. Here we introduce a novel approach to study neurogenesis in the ENS using an ex vivo organotypic tissue culturing system. Culturing longitudinal muscle and myenteric plexus tissue, we show that the enteric nervous system has tremendous replicative capacity with the majority of neural crest cells demonstrating EdU uptake by 48 hours. EdU+ cells express both neuronal and glial markers. Proliferation appears dependent on the PTEN/PI3K/Akt pathway with decreased PTEN mRNA expression and increased PTEN phosphorylation (inactivation) corresponding to increased Akt activity and proliferation. Inhibition of PTEN with bpV(phen) augments proliferation while , a PI3K inhibitor, blocks it. These data suggest that the ENS is capable of neurogenesis in a PTEN dependent manner. LY294002相似文献
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Garima Singhal ffolliott Martin Fisher Melissa J. Chee Tze Guan Tan Abdelfattah El Ouaamari Andrew C. Adams Robert Najarian Rohit N. Kulkarni Christophe Benoist Jeffrey S. Flier Eleftheria Maratos-Flier 《PloS one》2016,11(2)
Fibroblast growth factor 21 (FGF21) is an important endocrine metabolic regulator expressed in multiple tissues including liver and adipose tissue. Although highest levels of expression are in pancreas, little is known about the function of FGF21 in this tissue. In order to understand the physiology of FGF21 in the pancreas, we analyzed its expression and regulation in both acinar and islet tissues. We found that acinar tissue express 20-fold higher levels than that observed in islets. We also observed that pancreatic FGF21 is nutritionally regulated; a marked reduction in FGF21 expression was noted with fasting while obesity is associated with 3–4 fold higher expression. Acinar and islet cells are targets of FGF21, which when systemically administered, leads to phosphorylation of the downstream target ERK 1/2 in about half of acinar cells and a small subset of islet cells. Chronic, systemic FGF21 infusion down-regulates its own expression in the pancreas. Mice lacking FGF21 develop significant islet hyperplasia and periductal lymphocytic inflammation when fed with a high fat obesogenic diet. Inflammatory infiltrates consist of TCRb+ Thy1+ T lymphocytes with increased levels of Foxp3+ regulatory T cells. Increased levels of inflammatory cells were coupled with elevated expression of cytokines such as TNFα, IFNγ and IL1β. We conclude that FGF21 acts to limit islet hyperplasia and may also prevent pancreatic inflammation. 相似文献
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A proteomics approach to identifying key protein targets involved in VEGF inhibitor mediated attenuation of bleomycin‐induced pulmonary fibrosis 下载免费PDF全文
Yogesh M. Kulkarni Sucharita Dutta Anand Krishnan V. Iyer Rajkumar Venkatadri Vivek Kaushik Vani Ramesh Clayton A. Wright Oliver John Semmes Juan S. Yakisich Neelam Azad 《Proteomics》2016,16(1):33-46
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with a life expectancy of less than 5 years post diagnosis for most patients. Poor molecular characterization of IPF has led to insufficient understanding of the pathogenesis of the disease, resulting in lack of effective therapies. In this study, we have integrated a label‐free LC‐MS based approach with systems biology to identify signaling pathways and regulatory nodes within protein interaction networks that govern phenotypic changes that may lead to IPF. Ingenuity Pathway Analysis of proteins modulated in response to bleomycin treatment identified PI3K/Akt and Wnt signaling as the most significant profibrotic pathways. Similar analysis of proteins modulated in response to vascular endothelial growth factor (VEGF) inhibitor (CBO‐P11) treatment identified natural killer cell signaling and PTEN signaling as the most significant antifibrotic pathways. Mechanistic/mammalian target of rapamycin (mTOR) and extracellular signal‐regulated kinase (ERK) were identified to be key mediators of pro‐ and antifibrotic response, where bleomycin (BLM) treatment resulted in increased expression and VEGF inhibitor treatment attenuated expression of mTOR and ERK. Using a BLM mouse model of pulmonary fibrosis and VEGF inhibitor CBO‐P11 as a therapeutic measure, we identified a comprehensive set of signaling pathways and proteins that contribute to the pathogenesis of pulmonary fibrosis that can be targeted for therapy against this fatal disease. 相似文献
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Pradip B. Ranaware Anamika Mishra Periyasamy Vijayakumar Pradeep N. Gandhale Himanshu Kumar Diwakar D. Kulkarni Ashwin Ashok Raut 《PloS one》2016,11(4)
The molecular pathogenesis of avian influenza infection varies greatly with individual bird species and virus strain. The molecular pathogenesis of the highly pathogenic avian influenza virus (HPAIV) or the low pathogenic avian influenza virus (LPAIV) infection in avian species remains poorly understood. Thus, global immune response of chickens infected with HPAI H5N1 (A/duck/India/02CA10/2011) and LPAI H9N2 (A/duck/India/249800/2010) viruses was studied using microarray to identify crucial host genetic components responsive to these infection. HPAI H5N1 virus induced excessive expression of type I IFNs (IFNA and IFNG), cytokines (IL1B, IL18, IL22, IL13, and IL12B), chemokines (CCL4, CCL19, CCL10, and CX3CL1) and IFN stimulated genes (OASL, MX1, RSAD2, IFITM5, IFIT5, GBP 1, and EIF2AK) in lung tissues. This dysregulation of host innate immune genes may be the critical determinant of the severity and the outcome of the influenza infection in chickens. In contrast, the expression levels of most of these genes was not induced in the lungs of LPAI H9N2 virus infected chickens. This study indicated the relationship between host immune genes and their roles in pathogenesis of HPAIV infection in chickens. 相似文献
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Neethu Robinson Ali Danish Zaidi Mohit Rana Vinod A. Prasad Cuntai Guan Niels Birbaumer Ranganatha Sitaram 《PloS one》2016,11(7)
Recently, studies have reported the use of Near Infrared Spectroscopy (NIRS) for developing Brain–Computer Interface (BCI) by applying online pattern classification of brain states from subject-specific fNIRS signals. The purpose of the present study was to develop and test a real-time method for subject-specific and subject-independent classification of multi-channel fNIRS signals using support-vector machines (SVM), so as to determine its feasibility as an online neurofeedback system. Towards this goal, we used left versus right hand movement execution and movement imagery as study paradigms in a series of experiments. In the first two experiments, activations in the motor cortex during movement execution and movement imagery were used to develop subject-dependent models that obtained high classification accuracies thereby indicating the robustness of our classification method. In the third experiment, a generalized classifier-model was developed from the first two experimental data, which was then applied for subject-independent neurofeedback training. Application of this method in new participants showed mean classification accuracy of 63% for movement imagery tasks and 80% for movement execution tasks. These results, and their corresponding offline analysis reported in this study demonstrate that SVM based real-time subject-independent classification of fNIRS signals is feasible. This method has important applications in the field of hemodynamic BCIs, and neuro-rehabilitation where patients can be trained to learn spatio-temporal patterns of healthy brain activity. 相似文献
66.
Sanjay Kini Veena G. Kamath Muralidhar M. Kulkarni Asha Kamath Siddharudha Shivalli 《PloS one》2016,11(4)
IntroductionAccording to Joint National Committee-7 (JNC-7) guidelines, a systolic blood pressure (SBP) of 120 to 139 mm Hg and/or diastolic blood pressure (DBP) of 80 to 89 mm Hg is considered as pre-hypertension. Existing evidence suggest that the cardiovascular morbidities are increasing among pre-hypertensive individuals compared to normal.ObjectiveTo assess the magnitude and factors associated with pre-hypertension among young adults (20–30 years) in coastal villages of Udupi Taluk (an area of land with a city or town that serves as its administrative centre and usually a number of villages), Udupi District, Karnataka state, India.DesignCommunity based cross sectional studySetting6 (out of total 14) coastal villages of Udupi Taluk, Karnataka state, India.Sample1,152 young adults (age group: 20–30 years) selected by stratified random sampling in 6 coastal villages of Udupi Taluk, Karnataka state, IndiaMethodA semi structured pre-tested questionnaire was used to elicit the details on socio-demographic variables, dietary habits, tobacco use, alcohol consumption, physical activity, family history of hypertension and stress levels. Anthropometric measurements and blood pressure were recorded according to standard protocols. Serum cholesterol was measured in a sub sample of the study population. Multivariate logistic regression was applied to identify the independent correlates of pre-hypertension among young adults (20–30 years).ResultsThe prevalence of pre-hypertension in the study population was 45.2% (95%CI: 42.4–48). Multivariate logistic regression analysis revealed that age group of 25–30 years (adj OR: 4.25, 95% CI: 2.99–6.05), white collared (adj OR: 2.29, 95% CI: 1.08–4.85) and skilled occupation (adj OR: 3.24, 95% CI: 1.64–6.42), students (adj OR: 2.46, 95% CI: 1.22–4.95), using refined cooking oil (adj OR: 0.53, 95% CI: 0.29–0.95), extra salt in meals (adj OR: 2.46, 95% CI: 1.52–3.99), salty food items (adj OR: 6.99, 95% CI: 3.63–13.48), pre-obese (adj OR: 1.66, 95% CI: 1.03–2.67) and obese (adj OR: 9.16, 95% CI: 2.54, 36.4) were the significant correlates of pre-hypertension.ConclusionIn the study population, prevalence of pre-hypertension among young adults (20–30 years) was high (45.2%). Biological (age 25–30 years, pre-obesity and obesity) and behavioral (sedentary occupation, intake of extra salt in meals/salty food and not using refined cooking oil) factors were associated with pre-hypertension. Study emphasizes the need of community based screening of pre-hypertension under National Rural Health Mission. It also provides apt information for the evidence based designing of interventions for lifestyle modifications among high risk young adults in the study area. 相似文献
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The elderly exhibit increased mortality to influenza viral infection for unclear reasons. Mice are frequently used to model how aging impacts disease. Several studies have shown that aged mice exhibit an increased mortality to influenza virus, but two recent studies demonstrated the opposite. These two studies administered the virus intranasally in 20 µL, whereas the other studies used a viral inoculum in at least 30 µL. To determine whether the volume of the inoculum could explain the conflicting reports, we infected young and aged mice via intranasal instillation of 40 µL or 20 µL containing 1 x 104 plaque‐forming units (PFU) of H1N1 influenza virus. We found that intranasal administration of 40 µL but not 20 µL of inoculum resulted in age‐dependent mortality in mice. Compared to aged mice infected with 40 µL inoculum, those infected with 20 µL inoculum showed reduced levels of live virus and IFN‐β in the lung 3 days postinfection. Furthermore, aged mice administered 40 µL of Evans blue intranasally displayed increased dye retention in their bronchoalveolar lavage fluid compared to those administered 20 µL of Evans blue. Our data demonstrate that the inoculating volume of virus is critical for adequate delivery of influenza virus to the lung and thus for efficient infection of aged mice. These findings shed light on discrepant results in the literature regarding aged mice and influenza infection, and establish that mice can be used to examine how aging impacts the response to this biomedically important infection. 相似文献
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