Effect of oxidative stress on ABC transporters: contribution to epilepsy pharmacoresistance

Epilepsy is a neurological disorder affecting around 1%-2% of population worldwide and its treatment includes use of antiepileptic drugs to control seizures. Failure to respond to antiepileptic drug therapy is a major clinical problem and over expression of ATP-binding cassette transporters is considered one of the major reasons for pharmacoresistance. In this review, we have summarized the regulation of ABC transporters in response to oxidative stress due to disease and antiepileptic drugs. Further, ketogenic diet and antioxidants were examined for their role in pharmacoresistance. The understanding of signalling pathways and mechanism involved may help in identifying potential therapeutic targets and improving drug response

Oxidative Stress: Role and Response of Short Guanine Tracts at Genomic Locations

Over the decades, oxidative stress has emerged as a major concern to biological researchers. It is involved in the pathogenesis of various lifestyle-related diseases such as hypertension, diabetes, atherosclerosis, and neurodegenerative diseases. The connection between oxidative stress and telomere shortening via oxidative guanine lesion is well documented. Telomeres are confined to guanine rich ends of chromosomes. Owing to its self-association properties, it adopts G-quadruplex structures and hampers the overexpression of telomerase in the cancer cells. Guanine, being the most oxidation prone nucleobase, when structured in G-quadruplex entity, is found to respond peculiarly towards oxidative stress. Interestingly, this non-Watson-Crick structural feature exists abundantly in promoters of various oncogenes, exons and other genomic locations. The involvement of G-quadruplex architecture in oncogene promoters is well recognized in gene regulation processes. Development of small molecules aimed to target G-quadruplex structures, have found to alter the overexpression of oncogenes. The interaction may lead to the obstruction of diseased cell having elevated level of reactive oxygen species (ROS). Thus, presence of short guanine tracts (Gn) forming G-quadruplexes suggests its critical role in oxidative genome damage. Present review is a modest attempt to gain insight on the association of oxidative stress and G-quadruplexes, in various biological processes

YIOOP FULL HISTORICAL INDEXING IN CACHE NAVIGATION

This project adds new cache-related features to Yioop, an Open Source, PHP-based search engine. Search engines often maintain caches of pages downloaded by their crawler. Commercial search engines like Google display a link to the cached version of a web page along with the search results for that particular web page. The first feature enables users to navigate through Yioop\u27s entire cache. When a cached page is displayed along with its contents, links to cached pages saved in the past are also displayed. The feature also enables users to navigate cache history based on year and month. This feature is similar in function to the Internet Archive as it maintains snapshots of the web taken at different times. The contents of a web page can change over time. Thus, a search engine caching web pages has to make sure that the cached pages are fresh. The second feature of this project implements cache validation using information obtained from web page headers. The cache validation mechanism is implemented using Entity Tags and Expires header. The cache validation feature is then tested for effect on crawl speed and savings in bandwidth

NATURAL RESOURCES AND POLICIES FOR COMMUNITY-BASED ECOTOURISM: AN UTTARAKHAND PERSPECTIVE

This paper in particular deals with the analysis and reviews of the ecotourism policies and the framework of the state of Uttarakhand and the Indian government. In general, it evaluates and discusses the future and significance of the natural resources for the development of the community-based ecotourism in Uttarakhand for the sustainable development of the villages including conservation of biological diversity. This paper argues that the homestay programme, if encouraged, might help the state to achieve its goal of ecotourism and the green economy. Tourism was given an industry status by the government of Uttarakhand in 2018, providing attractive incentives and subsidies. Nevertheless, there is still a need for the appropriate policy framework for the better management of the natural resources, development and the training of the various stakeholders and the entrepreneurs involved in the community-based ecotourism industry

Early Warning Signals for Cryptocurrency Market States

Being archetypal complex systems, financial markets exhibit rich set of dynamics in their interactions. In this paper, we focus on the recently evolved cryptocurrency market as an example of a complex system and analyse the evolution of cross correlation structure of cryptocurrencies in the 5 year period from 2017 to 2022. We observe characteristic correlation structures in the observation time window duration and use these specific structures to cluster the cryptocurrency market in 4 market states

Viral Induced Oxidative and Inflammatory Response in Alzheimer's Disease Pathogenesis with Identification of Potential Drug Candidates: A Systematic Review using Systems Biology Approach

Alzheimer's disease (AD) is genetically complex with multifactorial etiology. Here, we aim to identify the potential viral pathogens leading to aberrant inflammatory and oxidative stress response in AD along with potential drug candidates using systems biology approach. We retrieved protein interactions of amyloid precursor protein (APP) and tau protein (MAPT) from NCBI and genes for oxidative stress from NetAge, for inflammation from NetAge and InnateDB databases. Genes implicated in aging were retrieved from GenAge database and two GEO expression datasets. These genes were individually used to create protein-protein interaction network using STRING database (score≥0.7). The interactions of candidate genes with known viruses were mapped using virhostnet v2.0 database. Drug molecules targeting candidate genes were retrieved using the Drug- Gene Interaction Database (DGIdb). Data mining resulted in 2095 APP, 116 MAPT, 214 oxidative stress, 1269 inflammatory genes. After STRING PPIN analysis, 404 APP, 109 MAPT, 204 oxidative stress and 1014 inflammation related high confidence proteins were identified. The overlap among all datasets yielded eight common markers (AKT1, GSK3B, APP, APOE, EGFR, PIN1, CASP8 and SNCA). These genes showed association with hepatitis C virus (HCV), Epstein- Barr virus (EBV), human herpes virus 8 and Human papillomavirus (HPV). Further, screening of drugs targeting candidate genes, and possessing anti-inflammatory property, antiviral activity along with a suggested role in AD pathophysiology yielded 12 potential drug candidates. Our study demonstrated the role of viral etiology in AD pathogenesis by elucidating interaction of oxidative stress and inflammation causing candidate genes with common viruses along with the identification of potential AD drug candidates

Structural polymorphism exhibited by a quasipalindrome present in the locus control region (LCR) of the human β-globin gene cluster

Structural polymorphism of DNA is a widely accepted property. A simple addition to this perception has been our recent finding, where a single nucleotide polymorphism (SNP) site present in a quasipalindromic sequence of β-globin LCR exhibited a hairpin-duplex equilibrium. Our current studies explore that secondary structures adopted by individual complementary strands compete with formation of a perfect duplex. Using gel-electrophoresis, ultraviolet (UV)-thermal denaturation, circular dichroism (CD) techniques, we have demonstrated the structural transitions within a perfect duplex containing 11 bp quasipalindromic stretch (TGGGG(G/C)CCCCA), to hairpins and bulge duplex forms. The extended version of the 11 bp duplex, flanked by 5 bp on both sides also demonstrated conformational equilibrium between duplex and hairpin species. Gel-electrophoresis confirms that the duplex coexists with hairpin and bulge duplex/cruciform species. Further, in CD spectra of duplexes, presence of two overlapping positive peaks at 265 and 285 nm suggest the features of A- as well as B-type DNA conformation and show oligomer concentration dependence, manifested in A → B transition. This indicates the possibility of an architectural switching at quasipalindromic region between linear duplex to a cruciform structure. Such DNA structural variations are likely to be found in the mechanics of molecular recognition and manipulation by proteins

Stress and Nutritional Status of Individuals in Uttarakhand, Northern India: Differential Effect of Gender

Background: Uttarakhand, Northern India is facing challenges in the issues concerning public health. Hence, researches identifying the stressors and nutritional factors influencing health are encouraged. This study attempts to assess the stress levels and nutritional status. Gender differences are also measured in the same. Methods: Stress and nutritional status related information was gathered (Nov, 2012-June, 2013) from 118 individuals residing in Uttarakhand state. Stress level was assessed using Personal Stress Score Inventory. Anthropometric details and dietary intake (3 day food recall method) were collected. Nutrient intake were calculated and compared with recommended dietary allowance (RDA) for Indians. T-test and Chi-square (χ²) were performed to measure the gender difference in studied variables. Results: 66.6% of females and 85.4% of males reported moderate stress (31-79). Males were seen to be more stressed then females, though no significant difference was seen. A significant difference in BMI (Body mass Index) was seen between males (24.1 kg/m2) and females (21.5 kg/m2). The study sample was found to be deficient in iron and zinc when compared with RDA. Females suffering from various level of stress had significantly lower levels of energy, protein, zinc than males. Conclusion: Majority of subjects were suffering from moderate level of stress. The anthropometric status of subjects was good, though females showed significantly lower intake of nutrients compared to men. Poor intake of iron and zinc points towards a possibility of hidden hunger. Hence, psychological and nutritional counseling may be required

Micro-histological analysis of faeces of Chukar partridge Alectoris chukar gray in Garhwal Himalaya, Uttarakhand, India

In vivo studies on the feeding of Chukar partridge (Alectoris chukar Gray) in Garhwal Himalaya, Uttarakhand and micro-histological analysis of 104 samples of its faeces were investigated during January 2011 to December 2012, to get information on vegetative and non-vegetative diet and feeding behaviour. Plant matter constituted a major portion of the faecal content (87.73±4.31?g) and represented by 14 families. Non- vegetative matter could be recorded as 9.36±1.46?g of dry weight which represented by 8 orders of the arthropods. Fine organic matter + grits constitute was found to be 2.84%±1.17?g in faecal content. Saxifragaceae, Graminaceae, Rosaceae, Poaceae and Fabaceae were found the best plant families for Chukar diet while arthropod insects order like Diptera, Dissotera, Hymenoptera and Araneae remained favorite feeds. Flowers and fruits of Rhus parviflora, leaves of Rumax, roots/ tuber of Vigna and fruits of Rubus were found important diet of Chukar partridge along with Triticum in Rabi crop and Oryza in Kharif. Flies, grasshoppers, spiders were observed the main insects diet of Chukar partridge