Island biogeography and human practices drive ecological connectivity in mosquito species richness in the Lakshadweep Archipelago.

Mosquitoes are globally distributed and adapted to a broad range of environmental conditions. As obligatory hosts of many infectious pathogens, mosquito abundance and distribution are primarily determined by the presence and quality of larval habitats. To understand the dynamics and productivity of larval habitats in changing island environments, we conducted a four-month mosquito survey across ten inhabited islands in the Lakshadweep archipelago. Using fine-resolution larval habitat mapping, we recorded 7890 mosquitoes representing 13 species and 7 genera. Of these, four species comprised 95% of the total collections-Aedes albopictus (Stegomyia) was the dominant species followed by Armigeres subalbatus, Culex quinquefasciatus and Malaya genurostris. We found larval species richness was positively associated with the island area and mosquito larval richness (Chao1 estimator) was higher in artificial habitats than in natural habitats. Furthermore, mosquito species composition did not deteriorate with distance between islands. Mosquito abundance by species was associated with microclimatic variables-pH and temperature. We detected co-existence of multiple species at a micro-habitat level with no evidence of interactions like competition or predation. Our study analyzed and identified the most productive larval habitats -discarded plastic container and plastic drums contributing to high larval indices predicting dengue epidemic across the Lakshadweep islands. Our data highlight the need to devise vector control strategies by removal of human-induced plastic pollution (household waste) which is a critical driver of disease risk.

Knowledge and attitudes about the use of emergency contraception among college students in Tamil Nadu, India.

BACKGROUND: In India, a large number of pregnancies are unplanned resulting in unsafe and illegal abortion. For every legal abortion, 10 to 11 illegal abortions are occurring which endangers the health and survival of the women. In recent years, there is an increase in unwanted and unintended pregnancy at the early age group. Usage of emergency contraception (EC) can decrease the unwanted pregnancy and provide a healthier life. AIM: The aim of study is to assess the knowledge and attitude regarding EC among college students in Thiruvarur District, Tamil Nadu, India. METHODS: A cross-sectional study was conducted among the college students of Thiruvarur district, Tamil Nadu, India. A total of 758 students were selected by convenient sampling technique. Data was collected by administering a pretested semi-structured questionnaire. RESULTS: Out of 758 students, 183(24%) heard about EC. The commonest source of information was the internet 91 (49.7%). The majority 116 (63.4%) knew that it does not prevent STDs. Of those who were aware, 42% were aware of 42.6% are aware of the time limit to use EC. The knowledge level of about the EC was moderate (60.1%), and it was significantly (p < 0.05) more among students > 25 years old, married participants, students in private institution, of lower socio-economic status, Muslim students and days' scholars. The negative attitude towards EC was 59%. Nearly 38.8% believed that the EC will affect the next menstrual period, and 35.5% informed it will increase high risk behaviour among adults. The attitude level was significantly associated with the same factors associated with the awareness level with the factors Christian religion replacing Muslim and higher socioeconomic class replacing lower class participants. CONCLUSION: The knowledge level of the studied college students was moderate, and they mostly had negative attitude towards the EC. Reproductive health education should be given in educational institutions to promote awareness and to remove misconceptions about EC.

A Mechanistic Review on Medicinal Mushrooms-Derived Bioactive Compounds: Potential Mycotherapy Candidates for Alleviating Neurological Disorders.

According to the World Health Organization, neurological and neurodegenerative diseases are highly debilitating and pose the greatest threats to public health. Diseases of the nervous system are caused by a particular pathological process that negatively affects the central and peripheral nervous systems. These diseases also lead to the loss of neuronal cell function, which causes alterations in the nervous system structure, resulting in the degeneration or death of nerve cells throughout the body. This causes problems with movement (ataxia) and mental dysfunction (dementia), both of which are commonly observed symptoms in Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. Medicinal mushrooms are higher fungi with nutraceutical properties and are low in calories and fat. They are also a rich source of nutrients and bioactive compounds such as carbohydrates, proteins, fibers, and vitamins that have been used in the treatment of many ailments. Medicinal mushrooms such as Pleurotus giganteus, Ganoderma lucidium, and Hericium erinaceus are commonly produced worldwide for use as health supplements and medicine. Medicinal mushrooms and their extracts have a large number of bioactive compounds, such as polysaccharide ß-glucan, or polysaccharide-protein complexes, like lectins, lactones, terpenoids, alkaloids, antibiotics, and metal-chelating agents. This review will focus on the role of the medicinal properties of different medicinal mushrooms that contain bioactive compounds with a protective effect against neuronal dysfunction. This information will facilitate the development of drugs against neurodegenerative diseases.

Seasonal variations of dengue vector mosquitoes in rural settings of Thiruvarur district in Tamil Nadu, India.

BACKGROUND & OBJECTIVES: Mosquitoes are vectors of several important vector-borne diseases (VBDs) like malaria, dengue, chikungunya, Japanese encephalitis (JE) and lymphatic filariasis (LF). Globally, these VBDs are of major public health concern including India. The information on vector mosquitoes from Thiruvarur district in Tamil Nadu state remains largely either unknown or undocumented. The present study was, therefore, undertaken to find out the seasonal variation in mosquitoes with special reference to dengue vectors in rural areas of Thiruvarur district, Tamil Nadu, India. METHODS: Surveillance of immature vector mosquitoes was undertaken from March 2018 to February 2019. The emerged adults were identified to find out the composition of mosquito species prevalent in the district. The seasonal variations of the mosquitoes especially dengue vectors were analysed for summer (March-July) spring (August-November) and winter (December-February) seasons in all the blocks of Thiruvarur district. RESULTS: A total of 4879 mosquitoes emerged from the immature collection and the species identification revealed the prevalence of both vector and non-vector species. Five important mosquito vectors collected were -Aedes albopictus, Ae. aegypti, Culex tritaeniorhynchus, Cx. gelidus, and Cx. quinquefasciatus. Other mosquito species collected were Lutzia fuscana, Anopheles barbirostris, An. subpictus, and Armigeres (Armigeres) subalbatus. During the spring season, the dengue vectors showed high indices of breateau index (BI), ranging from 16 to 120; besides, container index (CI) ranging from14.29 to 68.57 and pupal index (PI) from 53.33 to 295 among the study blocks. The major breeding sites were discarded plastic containers, discarded tyres, open sintex tanks (water storage tanks), cement tanks, discarded fibre box, pleated plastic sheets, tree holes, bamboo cut stumps, coconut spathe, and coconut shells. INTERPRETATION & CONCLUSION: The immature vector surveillance revealed seasonal variations in the entomological indices of Aedes breeding potential. The high indices observed indicate high Aedes breeding density and, therefore, a higher risk for dengue/chikungunya outbreaks in rural areas of Thiruvarur district. The present finding warrants intensive surveillance and follow up vector control measures to avert outbreaks and prevent vector-borne diseases. Health education and the community participation in awareness camps prior to monsoon and societal commitment will help in strengthening source reduction, anti-larval operations and anti-adult measures to tackle vector-borne diseases especially dengue.

Prevalence of disease vectors in Lakshadweep Islands during post-monsoon season.

BACKGROUND & OBJECTIVES: : Increase of vector-borne diseases (VBDs) in India has posed a question on the situation in Lakshadweep Islands, where VBDs are reported from time-to-time. The present investigation was aimed to assess the faunastic situation of the prevailing vectors along with their breeding sites in different islands of the Lakshadweep. METHODS: : Extensive surveys were carried out from November 2017 to January 2018 (post-monsoon season) randomly in the nine inhabited islands of Lakshadweep for conducting faunastic studies on mosquitoes and to know the basic binomics like breeding and resting preference of mosquitoes. The study islands included, Kavaratti, Agatti, Chetlat, Bitra, Amini, Kadmath, Andrott, Kalpeni and Kiltan. Both immature and adult collections were carried out by standard/appropriate sampling techniques. The obtained data were calculated and analysed in terms of different entomological indices. RESULTS: : A total of 3356 mosquitoes were collected during the study period which comprised of 16 species from nine genera. Out of the 16 species, six belonged to mosquito vectors. The collection included malaria vector, Anopheles stephensi; Japanese encephalitis vector, Culex tritaeniorhynchus; Bancroftian filariasis vector, Cx. quinquefasciatus; Brugian filariasis vector, Mansonia uniformis; and dengue and chikungunya vectors, Stegomya albopicta and St. aegypti. Stegomya albopicta was the most predominant species observed constituting 54% of the catch, followed by Cx. quinquefasciatus, An. stephensi, Cx. tritaeniorhynchus, and St. aegypti constituting 10.5, 6, 3 and 1.2%, respectively. Apart from vector species many non-vectors such as Heizmannia chandi, An. subpictus, An. varuna, Cx. sitiens, Cx. minutissimus, Cx. rubithoracis, Fredwardsius vittatus, Lutzia fuscana, Malaya genurostris and Armigeres subalbatus were also present in the study area. In Kavaratti Island, the capital of Lakshadweep, a non-vector species of sandfly, Sergentomyia (Parrotomyia) babu was observed during the indoor resting collection. The major breeding sites which supported various mosquito species included, discarded plastic containers, tree holes, open sintex tanks (water storage tanks), unused wells, discarded tyres, discarded iron pots, unused and damaged boats, cement tanks, pleated plastic sheets, coral holes, pits and irrigation canals, discarded washing machines, and Colocasia plant leaf axils. Breteau index ranged between 65.3 and 110, CI ranged between 63.64 and 72.41; and HI ranged between 38.46 and 70 among the various islands. INTERPRETATION & CONCLUSION: : Entomological indices such as house index (HI), breteau index (BI) and pupal index (PI) were high in all the nine islands and exceeded the threshold levels specified by WHO, indicating high risk for dengue virus transmission in case of outbreaks. Occurrence of vector as well as non-vector species indicates that the global change in climate is causing notable changes in terms of breeding of vector and non-vector species in the islands. With the reported cases of VBDs and the presence of vectors species in Lakshadweep Islands, a stringent control measure needs to be implemented at the Lakshadweep Islands.

CD8+ T cells of chronic HCV-infected patients express multiple negative immune checkpoints following stimulation with HCV peptides.

Hepatitis C virus (HCV)-specific CD4+ and CD8+ T cells are key to successful viral clearance in HCV disease. Accumulation of exhausted HCV-specific T cells during chronic infection results in considerable loss of protective functional immune responses. The role of T-cell exhaustion in chronic HCV disease remains poorly understood. Here, we studied the frequency of HCV peptide-stimulated T cells expressing negative immune checkpoints (PD-1, CTLA-4, TRAIL, TIM-3 and BTLA) by flow cytometry, and measured the levels of Th1/Th2/Th17 cytokines secreted by T cells by a commercial Multi-Analyte ELISArray™ following in vitro stimulation of T cells using HCV peptides and phytohemagglutinin (PHA). HCV peptide-stimulated CD4+ and CD8+ T cells of chronic HCV (CHC) patients showed significant increase of CTLA-4. Furthermore, HCV peptide-stimulated CD4+ T cells of CHC patients also displayed relatively higher levels of PD-1 and TRAIL, whereas TIM-3 was up-regulated on HCV peptide-stimulated CD8+ T cells. Whereas the levels of IL-10 and TGF-ß1 were significantly increased, the levels of pro-inflammatory cytokines IL-2, TNF-α, IL-17A and IL-6 were markedly decreased in the T cell cultures of CHC patients. Chronic HCV infection results in functional exhaustion of CD4+ and CD8+ T cells likely contributing to viral persistence.

Cigarette smoke and related risk factors in neurological disorders: An update.

Cigarette smoking is known to be harmful to health, and is considered the main cause of death worldwide, especially in India. Among the well-distinguished diseases related to smoking are, chronic obstructive pulmonary disease, oral and peripheral cancers, and cardiovascular complications. However, the impact of cigarette smoking on neurocognitive and neuropathological effects, including anxiety, Alzheimer's disease, Parkinson's disease, ischemic stroke, and blood-brain barrier dysfunction, still remains unclear. Cigarette smoke consists of more than 4500 toxic chemicals that combine to form free radicals, which lead to oxidative stress-associated neurological disorders. Herein, we discuss the role of antioxidant agents in delaying or attenuating disease complications. In addition, in this review, we discuss the neuropathological effect of cigarette smoke and its interference in neurodegeneration.

A structural insight into the negative effects of opioids in analgesia by modulating the TLR4 signaling: An in silico approach.

Opioids are considered the gold standard therapy for pain. However, TLR-dependent negative effects in analgesia have highlighted the complexities in the pharmacodynamics of opioids. While successive studies have reported that morphine and Morphine-3-glucuronide (M3G) activate the TLR4 pathway, the structural details of this mechanism are lacking. Here, we have utilized various computational tools to reveal the structural dynamics of the opioid-bound TLR4/MD2 complex, and have proposed a potential TLR4 activation mechanism. Our results support previous findings, and include the novel insight that the stable binding of morphine and naloxone, but not M3G, in the MD2 cavity, is TLR4 dependent. Morphine interacts with MD2 near its Phe126 loop to induce the active conformation (MD2C); however, this binding is likely reversible, and the complex gains stability upon interaction with TLR4. M3G also induces the MD2C state, with both the Phe126 loop and the H1 loop being involved in MD2-M3G complex stability. Remarkably, naloxone, which requires TLR4 interaction for complex stability, switches the conformation of the gating loop to the inactive state (MD2°). Cumulatively, our findings suggest that ligand binding and receptor clustering occur successively in opioid-induced TLR4 signaling, and that MD2 plasticity and pocket hydrophobicity are crucial for the recognition and accommodation of ligands.

A systems biology and proteomics-based approach identifies SRC and VEGFA as biomarkers in risk factor mediated coronary heart disease.

Coronary heart disease (CHD) is the most common cause of death worldwide. The burden of CHD increases with risk factors such as smoking, hypertension, obesity and diabetes. Several studies have demonstrated the association of these classical risk factors with CHD. However, the mechanisms of these associations remain largely unclear due to the complexity of disease pathophysiology and the lack of an integrative approach that fails to provide a definite understanding of molecular linkage. To overcome these problems, we propose a novel systems biology approach that relates causative genes, interactomes and pathways to elucidate the risk factors mediating the molecular mechanisms and biomarkers for feasible diagnosis. The literature was mined to retrieve the causative genes of each risk factor and CHD to construct protein interactomes. The interactomes were examined to identify 298 common molecular signatures. The common signatures were mapped to the tissue network to synthesize a sub-network consisting of 82 proteins. Further, the dissection of the sub-network provides functional modules representing a diverse range of molecular functions, including the AKT/p13k, MAPK and wnt pathways. Also, the prioritization of functional modules identifies SRC, VEGFA and HIF1A as potential candidate markers. Further, we validate these candidates with the existing markers CRP, NOS3 and VCAM1 in the serum of 63 individuals, 33 with CHD and 30 controls, using ELISA. SRC, VEGFA, H1F1A, CRP and NOS3 were significantly altered in patients compared to controls. These results support the utility of these candidate markers for the diagnosis of CHD. Overall, our molecular observations indicate the influence of risk factors in the pathophysiology of CHD and identify serum markers for diagnosis.

Systems Biological Approaches Reveal Non-additive Responses and Multiple Crosstalk Mechanisms between TLR and GPCR Signaling.

A variety of ligands differ in their capacity to bind the receptor, elicit gene expression, and modulate physiological responses. Such receptors include Toll-like receptors (TLRs), which recognize various patterns of pathogens and lead to primary innate immune activation against invaders, and G-protein coupled receptors (GPCRs), whose interaction with their cognate ligands activates heterotrimeric G proteins and regulates specific downstream effectors, including immuno-stimulating molecules. Once TLRs are activated, they lead to the expression of hundreds of genes together and bridge the arm of innate and adaptive immune responses. We characterized the gene expression profile of Toll-like receptor 4 (TLR4) in RAW 264.7 cells when it bound with its ligand, 2-keto-3-deoxyoctonate (KDO), the active part of lipopolysaccharide. In addition, to determine the network communications among the TLR, Janus kinase (JAK)/signal transducer and activator of transcription (STAT), and GPCR, we tested RAW 264.7 cells with KDO, interferon-ß, or cAMP analog 8-Br. The ligands were also administered as a pair of double and triple combinations.

Drugs targeting Toll-like receptors.

Animals and plants are exposed to myriads of potential microbial invaders. In case of animals, Toll-like receptors (TLRs) act as the primary defense against infection by pathogens. Arguably, less is known regarding the activation of TLRs that connect the innate and adaptive immune systems. Some TLR ligands have been used as adjuvants in various vaccines and have gained a great deal of attention due to their ability to elicit an effective immune response. Understanding the intricate relationships between various molecules involved in TLR signaling and their positive or negative regulation is a key focus for the development of effective therapeutics. In this review, recent developments in TLR signaling that will be very important in providing new drug target molecules and a better understanding of molecular regulation of innate immunity are discussed.

Gene expression profiling of light-induced retinal degeneration in phototransduction gene knockout mice.

Exposure to light can induce photoreceptor cell death and exacerbate retinal degeneration. In this study, mice with genetic knockout of several genes, including rhodopsin kinase (Rhok-/-), arrestin (Sag-/-), transducin (Gnat1-/-), c-Fos (c-Fos-/-) and arrestin/transducin (Sag-/-/Gnat1-/-), were examined. We measured the expression levels of thousands of genes in order to investigate their roles in phototransduction signaling in light-induced retinal degeneration using DNA microarray technology and then further explored the gene network using pathway analysis tools. Several cascades of gene components were induced or inhibited as a result of corresponding gene knockout under specific light conditions. Transducin deletion blocked the apoptotic signaling induced by exposure to low light conditions, and it did not require c-Fos/AP-1. Deletion of c-Fos blocked the apoptotic signaling induced by exposure to high intensity light. In the present study, we identified many gene transcripts that are essential for the initiation of light-induced rod degeneration and proposed several important networks that are involved in pro- and anti-apoptotic signaling. We also demonstrated the different cascades of gene components that participate in apoptotic signaling under specific light conditions.

Characterization of phototransduction gene knockouts revealed important signaling networks in the light-induced retinal degeneration.

Understanding the molecular pathways mediating neuronal function in retinas can be greatly facilitated by the identification of genes regulated in the retinas of different mutants under various light conditions. We attempted to conduct a gene chip analysis study on the genes regulated during rhodopsin kinase (Rhok-/-) and arrestin (Sag-/-) knockout and double knockouts in mice retina. Hence, mice were exposed to constant illumination of 450 lux or 6,000 lux on dilated pupils for indicated periods. The retinas were removed after the exposure and processed for microarray analysis. Double knockout was associated with immense changes in gene expression regulating a number of apoptosis inducing transcription factors. Subsequently, network analysis revealed that during early exposure the transcription factors, p53, c-MYC, c-FOS, JUN, and, in late phase, NFkappaB, appeared to be essential for the initiation of light-induced retinal rod loss, and some other classical pro- and antipoptotic genes appeared to be significantly important as well.

Toll-like receptor signal transduction.

Toll-like receptors (TLRs) are the archetypal pattern recognition receptors in sensing exogenous pathogens. Activation of TLRs is a first line of defense of the immune system, leading to the activation and recruitment of neutrophils and macrophages to sites of infection and enhances antimicrobial activity. The TLR signaling through different intracellular molecules, such as MAP kinases and IkappaB kinases which are conserved signaling elements for many receptors, leads to a distinct set of proinflammatory gene expressions. However, how these pathways differentially and precisely control the transcription of identical genes remains largely unknown. Our review focuses on the details of up-to-date signaling molecules including negative regulators and their role in controlling innate immune response. We also stress the importance of developing systemic approaches for the global understanding of TLR signaling so that appropriate drug therapeutic targets can be identified for regulating inflammatory diseases.