Corticotropin releasing factor receptor type 1 signaling in epilepsy and traumatic brain injury

Stress increases the frequency by which epileptic seizures occur. Corticotropin-releasing factor (CRF) coordinates neuroendocrine, autonomic and behavioral response to stress. This thesis sought to study the cellular and molecular mechanisms by which CRF regulates the activity of neural circuits in the piriform cortex (PC) in normal and epileptic states. The PC is richly innervated by CRF and 5-HT containing axons arising from the central amygdala and raphe nucleus. CRFR1 and 5-HT2A/CRs have been shown to interact in a manner where CRFR activation subsequently potentiates the activity of 5-HT2A/CRs. The first purpose of this thesis was to determine how the activation of CRFR1 and/or 5-HT2Rs modulates PC activity at both the circuit and cellular level. Voltage-sensitive dye imaging showed that CRF acting through CRFR1 dampened activation of layer II in the PC and interneurons of the endopiriform nucleus. Application of the selective 5-HT2A/CRagonist 2,5-dimethoxy-4-iodoamphetamine (DOI) following CRFR1 activation potentiated this effect. Blocking the interaction between CRFR1 and 5-HT2R with a Tat-CRFR1-CT peptide abolished this potentiation. Application of forskolin did not mimic CRFR1 activity but instead blocked it, while a protein kinase A antagonist had no effect. However, activation and antagonism of protein kinase C (PKC) either mimicked or blocked CRF modulation respectively. DOI had no effect when applied alone indicating that the prior activation of CRFR1 receptors was critical for the DOI activity. This data shows that CRF and 5-HT, acting through 5-HT2A/CRs, reduce the activation of the PC. This modulation may be an important blunting mechanism of stressor behaviors mediated through the olfactory cortex. Anxiety and stress conditions induce neurons arising from the central amygdala and local interneurons to release CRF in PC, where it normally dampens excitability. The second aim of this thesis was to determine the role of CRF in stress associated epilepsy. We showed that CRF increased the excitability of PC in rats subjected to kindling, a model of temporal lobe epilepsy. In non-kindled rats, CRF activates its receptor, a G protein-coupled receptor (GPCR) and signals through a Gaq/11 mediated pathway as identified in the first aim of this thesis. After seizure induction, CRF signaling occurred through a pathway involving Gas. This change in signaling was associated with reduced abundance of regulator of G-protein signaling protein-2 (RGS2), which promotes the switch in CRFR1 signaling cascade to a Gas dependent mechanism. RGS2 knockout mice responded to CRF in a similar manner as epileptic rats. These observations indicate that seizures produce changes in neuronal signaling that can increase seizure occurrence by converting a beneficial stress response into an epileptic trigger. People with traumatic brain injury often develop epileptic seizures. The mechanisms underlying this are poorly understood. Considerable evidence suggests that association of stressful life experiences in brain injured patients lead them to develop post-traumatic stress disorder. CRF release in brain regions that are implicated in epileptogenesis make these situations worse. The third aim of this thesis was to understand the role of CRF in inducing excitability in PC after brain injury. We found that CRF has variable effects on the interneurons of ipsilateral and contralateral PC. Altogether, its actions lead to increased excitability of PC compared to healthy rat PC. The extent of excitability produced by CRF and the signaling mechanism of CRFR1 after brain injury were similar to CRF actions and CRFR1 signaling mechanism in kindling induced epilepsy. Overall, this thesis study provides the basic mechanisms by which certain forms of epilepsy, both stress and injury induced develops. It also points out the important discovery of this project that is, the capability of GPCRs to switch signaling cascades depending on the pathological condition of the brain

Cassava Bagasse: A Potential and Low Cost Substrate for Cellulase Production in an Economical Fermentation

ABSTRACT The purpose of this work was to produce cellulase by cellulomonas cellulans using solid waste materials such as cassava bagasse, pine leaves, wheat bran and rice bran in solid state fermentation (SSF). According to the maximum production of cellulase, cassava bagasse was selected as solid substrate among four solid substrates and used for further studies. Various nitrogen compounds like yeast extract, beef extract, peptone, malt extract were taken. Among them, yeast extract was selected as a best nitrogen source for cellulase production. Maximum production of cellulase was obtained at an initial moisture content of 80% with an initial pH of 6

ASSESSMENT OF SOCIAL VULNERABILITY TO THE IMPACT OF FLOOD HAZARD: A CASE STUDY OF KOPILI RIVER BASIN, ASSAM, INDIA

In the present study, an attempt is made to understand the impact on Social Vulnerability of the Kopili basin due to various severities of flood hazard. The flood hazard is generated using multi-temporal historical satellite based analysis and integration of annual flood inundation layers. The census of India data of 2001 and 2011 is spatially joined with village database to study the impact at village level. Using 5 Census variables from both Census 2001 & 2011 as vulnerability indicators, the Social Vulnerability Index (SVI) is derived and classified into various vulnerable zones namely Low, Moderate and High Vulnerable zones. The findings of the study show that the number of villages falling in Low and High Vulnerable zones had decreased during Census 2011 when compared to 2001 and a rise of 6% in villages falling in moderate vulnerable zones during 2011 is observed. The spatial database generated is useful to understand the impact of floods on the Social Vulnerability status of the basin and can be a useful input to further study the Physical, Economic and Environmental Vulnerabilities of the basin

Antenatal Care Services Utilization among the Antenatal and Postnatal Women in a Rural Area of South India: A Cross-Sectional Study

Introduction: Timely and quality antenatal care is a crucial determinant towards the prevention of maternal mortality, which is a significant developmental goal for developing countries, which contributes to more than 99% of maternal deaths worldwide. However, the lack of equitable access to quality ANC is a major challenge in resource-limited settings, particularly in developing countries like India. Objectives: To assess the utilization rates of antenatal care services among antenatal women and postnatal women and to determine the factors responsible forunder or non-utilization of antenatal care services (ANC). Method: The present study was conducted for a period offour months among antenatal and postnatal women in a rural area of South India. All antenatal and postnatal women except those who were not willing to participate and those who had MTP/abortion during the present pregnancy were included for the study. A pre tested semi structured questionnaire was used for collecting information regarding ANC utilization. Data was entered in Microsoft Excel and analyzed for descriptive and inferential statistics. Results: A total of 175 (125 antenatal and 50 postnatal) women were interviewed. Among them, 90.3% (92% antenatal and 86% postnatal) women had completely utilized ANC services. Among the postnatal women, those who had completely utilized ANC services, 11.6% had complications at the time of their delivery and those who had incompletely utilized ANC services, 57.1% had complications.The difference was found to be statistically significant (p<0.05).Only 87.4% women were covered in home visits and 28.6% of them were not given any prenatal advice.IFA tablets were taken adequately only by 57.7% women. Conclusion: The present study revealed that most of the women were aware about the antenatal services available and had registered their pregnancy early. Td immunization was done at right time. However antenatal home visits were not effectively implemented

Biochemical marker studies in tissue cultured and naturally growing plants of Asclepias curassavica (L)

ABSTRACT In the present study, the genetic stability of in vitro propagate

The empirical results of conditional analysis of principals' reasons in bullying teachers

Starting from the bullying of teachers by principals, this paper elaborates (a) how incompetency of management favours its emergence, (b) how teachers can see it, and (c) whether this problem affects the performance of teachers or not. The empirical results show that motivation, a positive workplace, and not being bullied or agitated by principals increase teachers' performance. The findings show that the teachers consider management's incompetency the major factor to be blamed. Collaboration between teachers can have a role in limiting this abuse. Because management is the key obligation for clearing the ethos and function of the company and clarifying the translation of words into the organization, there is some laggard of management in the way the control extracted from the structured authority is confused. Success strain!! In the light of the short- and long-term priorities and plans

The Empirical Results of Conditional Analysis of Principals Reasons in Bullying Teachers

Starting from the bullying of teachers by principals, this paper elaborates (a) how incompetency of management favours its emergence, (b) how teachers can see it, and (c) whether this problem affects the performance of teachers or not. The empirical results show that motivation, a positive workplace, and not being bullied or agitated by principals increase teachers performance. The findings show that the teachers consider managements incompetency the major factor to be blamed. Collaboration between teachers can have a role in limiting this abuse. Because management is the key obligation for clearing the ethos and function of the company and clarifying the translation of words into the organization, there is some laggard of management in the way the control extracted from the structured authority is confused. Success strain!! In the light of the short- and long-term priorities and plans, colleges and organized entity made up of people operating, supervised and operationally, can operate every phase so the activities can be orchestrated and integrated in an equilibrated manner

Characterization of glycine-N-acyltransferase like 1 (GLYATL1) in prostate cancer

BackgroundRecent microarray and sequencing studies of prostate cancer showed multiple molecular alterations during cancer progression. It is critical to evaluate these molecular changes to identify new biomarkers and targets. We performed analysis of glycine-N-acyltransferase like 1 (GLYATL1) expression in various stages of prostate cancer in this study and evaluated the regulation of GLYATL1 by androgen.MethodWe performed in silico analysis of cancer gene expression profiling and transcriptome sequencing to evaluate GLYATL1 expression in prostate cancer. Furthermore, we performed immunohistochemistry using specific GLYATL1 antibody using high-density prostate cancer tissue microarray containing primary and metastatic prostate cancer. We also tested the regulation of GLYATL1 expression by androgen and ETS transcription factor ETV1. In addition, we performed RNA-sequencing of GLYATL1 modulated prostate cancer cells to evaluate the gene expression and changes in molecular pathways.ResultsOur in silico analysis of cancer gene expression profiling and transcriptome sequencing we revealed an overexpression of GLYATL1 in primary prostate cancer. Confirming these findings by immunohistochemistry, we show that GLYATL1 is overexpressed in primary prostate cancer compared with metastatic prostate cancer and benign prostatic tissue. Low-grade cancers had higher GLYATL1 expression compared to high-grade prostate tumors. Our studies showed that GLYATL1 is upregulated upon androgen treatment in LNCaP prostate cancer cells which harbors ETV1 gene rearrangement. Furthermore, ETV1 knockdown in LNCaP cells showed downregulation of GLYATL1 suggesting potential regulation of GLYATL1 by ETS transcription factor ETV1. Transcriptome sequencing using the GLYATL1 knockdown prostate cancer cell lines LNCaP showed regulation of multiple metabolic pathways.ConclusionsIn summary, our study characterizes the expression of GLYATL1 in prostate cancer and explores the regulation of its regulation in prostate cancer showing role for androgen and ETS transcription factor ETV1. Future studies are needed to decipher the biological significance of these findings.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151252/1/pros23887.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151252/2/pros23887_am.pd