3'UTR-välitteinen hermokasvutekijöiden BDNF ja GDNF säätely

Neurotrophic factors such as brain¬-derived neurotrophic factor (BDNF) and glial cell line¬¬¬-derived neurotrophic factor (GDNF) are a family of proteins which play an important role inside and outside central nervous system. While precise regulation of BDNF and GDNF levels in time and space in an organism is crucial in determining the biological outcome, mechanisms involved in controlling their levels are not fully understood. Messenger RNAs (mRNAs) play a critical role in gene expression by conveying genetic information from DNA to protein synthesis. 3ʹ untranslated region (3ʹUTR) is a part of mRNA sequence which regulates gene expression by binding to microRNAs (miRs), RNA-binding proteins (RBPs) and other trans-acting factors. In this thesis, we investigated the 3ʹUTR mediated regulation of BDNF and GDNF. We demonstrate the presence of regulatory elements in the 3ʹUTR of BDNF and GDNF and, show that BDNF is regulated by four different miRs, namely miR-1, miR-10b, miR-155 and miR-191 and, RBP tristetraprolin (TTP) in different cell lines. Further, we show that GDNF is regulated by multiple miRs in cell lines and identify binding sites for miR-146a and miR-96 in the GDNF 3ʹUTR. Finally, we demonstrate that replacement of GDNF 3ʹUTR in mice with a 3ʹUTR with reduced responsiveness to negative regulators including miRs leads to elevated level of endogenous GDNF mRNA and protein in various organs with profound biological effects including in the brain dopamine system function in mice. We conclude that 3ʹUTR mediated regulation of BDNF and GDNF is biologically important and propose that 3ʹUTR replacement is an informative way to study gene function in vivo.Hermokasvutekijäperheeseen kuuluvilla aivoperäisellä hermokasvutekijällä (Brain derived neurotrophic factor, BDNF) ja gliasoluperäisellä hermokasvutekijällä (glial cell derived neurotrophic factor, GDNF) on tärkeä rooli sekä keskushermostossa että muualla elimistössä. Vaikka biologisen lopputuloksen tiedetään riippuvan BDNF:n ja GDNF:n tasojen tarkasta säätelystä ajan ja paikan suhteen, on säätelyn tarkka mekanismi vielä tuntematon. Lähetti-RNA (mRNA) molekyylit siirtävät DNA:n sisältämän geneettisen informaation proteiinisynteesiin. mRNA:n 3 pään kääntämätön alue (3 untranslated region, 3 UTR) on geenin säätelylle tärkeä alue, sillä se sisältää sitoutumiskohdan mikroRNA:lle (miR), RNA:han sitoutuville proteiineille (RNA-binding proteins, RBP) ja muille trans-vaikuttaville tekijöille. Tässä väitöskirjatyössä tutkittiin BDNF:n ja GDNF:n 3 UTR-välitteistä säätelyä. Käyttämällä eri solulinjoja voitiin osoittaa BDNF:llä ja GDNF:llä olevan 3 UTR-säätelyelementtejä ja että BDNF:n geeniä säätelee 4 eri miR:ta, miR-1, miR-10b, miR-155 ja miR-191 sekä RBP tristetraproliini (TTP). Solulinjoilla tehdyt kokeet osoittivat myös useiden miR:n säätelevän GDNF:n tasoja. Lisäksi voitiin tunnistaa miR-146a:n sekä miR-96:n sitoutumiskohdat GDNF:n 3 UTR-alueella. Kun hiirten GDNF 3 UTR korvattiin 3 UTR:llä, joka ei ole yhtä herkkä negatiivisille säätelytekijöille, kuten miR:lle, havaittiin endogeenisen GDNF:n mRNA- ja proteiinitasojen nousu useissa eri elimissä ja merkittävä muutos hiirten aivojen dopamiinijärjestelmässä. Tulosten perusteella BDNF:n ja GDNF:n 3 UTR-välitteinen säätely on biologisesti merkittävää ja 3 UTR:n korvaaminen on informatiivinen menetelmä tutkia geenien toimintaa in vivo

Review of Solar Energy Measurement System

The aim of this proposed work is to measure solar cell parameters through multiple sensor data acquisition. In this project, a solar panel is used that keeps monitoring the sunlight. Here different parameters of the solar panel like light intensity, voltage, current and the temperature are monitored and are sent to a remote PC using a RF 2.4 GHz serial link. Microcontroller used here is from PIC16F8 family

The Hadoop Distributed File System

The Hadoop Distributed File System (HDFS) is designed to store very large data sets reliably, and to stream those data sets at high bandwidth to user applications. In a large cluster, thousands of servers both host directly attached storage and execute user application tasks. By distributing storage and computation across many servers, the resource can grow with demand while remaining economical at every size. We describe the architecture of HDFS and report on experience using HDFS to manage 25 petabytes of enterprise data at Yahoo.

Biological activities and Phytochemical analysis of Zanthoxylum armatum DC. leaves and bark extracts collected from Kumaun region, Uttarakhand, India

The methanolic and chloroform extracts of leaves and bark of Zanthoxylum armatum DC. were evaluated for their phytochemical analysis and biological activities. In phytochemical analysis, fargsin was identified as major constituent in leaves methanolic and leaves chloroform extracts. t-butylamine and benzoxazole, 2-(isobutylamino) were identified as the major constituents in bark methanolic and bark chloroform extracts respectively. Both the extracts exhibited moderate antioxidant activity with IC50 values ranging from 19.42±0.07 to78.01±0.31 µg. These extracts also possess moderate anti-inflammatory activity with IB50 values ranging from 28.53 ± 0.06 to 89.80 ± 0.05 µg. Moderate anti-bacterial activity against E. coli and S. aureus has also been observed in both the extracts. The total flavonoids, orthodihydric phenols and phenolic contents were also quantified in the extracts. Based on these observations, it can be concluded that Zanthoxylum armatum DC. may be used as herbal antioxidant, food preservative, natural anti-inflammatory drug and natural bactericidal, besides generation of data base for judicious exploitation in future

Prevalence of leukoplakia, oral submucous fibrosis, papilloma and its relation with stress among green marbles mine laborers, India

Objectives: To determine the prevalence of leukoplakia, oral submucous fibrosis and papilloma among ?Green Marble Mines? laborer and uncover its relation with occupational stress. Methods: Mines were divided in four geographic zones, and participants were selected by stratified cluster sampling technique. A total of 513 subjects were included in final study which were alienated among the four age cohort 15-24 , 25-34 , 35-44, 45-54 respectively. The study was been conducted following the research methodology recommended by World Health Organization- Oral Health Surveys 1997. A questionnaire from ?Union of Shops, Distribution and Allied Worker (USDAW) Nationwide, Manchester? was used for stress assessment of mine workers and clinical examination for oral mucosa was conducted by one of the three examiner with the aid of an artificial light source. The kappa statistics for diagnosis of leukoplakia, oral submucous fibrosis and papilloma was determined (field teams versus expert) 0.81, 0.92 and 0.89 respectively two days prior to the examination. Data was analyzed using bivariate and multivariate analysis. Results: An overall elevated prevalence of all three oral-mucosal lesion was found among mine workers (36.7%), mainly leukoplakia affecting 171 mine workers (33.3%). The affected workers were having body problems like headache, backache and stressed due to under-payment. Individuals having papilloma have faced problem at work like noise, dust or fumes and poor maintenance of equipment. Multiple logistic regression analysis model of oral-mucosal lesion have shown highly significant relation (p<0.01) with increased stress, age, alcohol habits and malnutrition. Conclusion: The prevalence of oral mucosal lesion is higher, among marble mine laborers, and occupational stress can intensify the disease condition. Curative services along with prevention and stress reduction program, requires primary anticipation