Enhanced muscarinic M1 receptor gene expression in the corpus striatum of streptozotocin-induced diabetic rats

Acetylcholine (ACh), the first neurotransmitter to be identified, regulate the activities of central and peripheral functions through interactions with muscarinic receptors. Changes in muscarinic acetylcholine receptor (mAChR) have been implicated in the pathophysiology of many major diseases of the central nervous system (CNS). Previous reports from our laboratory on streptozotocin (STZ) induced diabetic rats showed down regulation of muscarinic M1 receptors in the brainstem, hypothalamus, cerebral cortex and pancreatic islets. In this study, we have investigated the changes of acetylcholine esterase (AChE) enzyme activity, total muscarinic and muscarinic M1 receptor binding and gene expression in the corpus striatum of STZ – diabetic rats and the insulin treated diabetic rats. The striatum, a neuronal nucleus intimately involved in motor behaviour, is one of the brain regions with the highest acetylcholine content. ACh has complex and clinically important actions in the striatum that are mediated predominantly by muscarinic receptors. We observed that insulin treatment brought back the decreased maximal velocity (Vmax) of acetylcholine esterase in the corpus striatum during diabetes to near control state. In diabetic rats there was a decrease in maximal number (Bmax) and affinity (Kd) of total muscarinic receptors whereas muscarinic M1 receptors were increased with decrease in affinity in diabetic rats. We observed that, in all cases, the binding parameters were reversed to near control by the treatment of diabetic rats with insulin. Real-time PCR experiment confirmed the increase in muscarinic M1 receptor gene expression and a similar reversal with insulin treatment. These results suggest the diabetes-induced changes of the cholinergic activity in the corpus striatum and the regulatory role of insulin on binding parameters and gene expression of total and muscarinic M1 receptors

Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A

<p>Abstact</p> <p>Background</p> <p>Gamma amino butyric acid (GABA), the principal inhibitory neurotransmitter in the cerebral cortex, maintains the inhibitory tones that counter balances neuronal excitation. When this balance is perturbed, seizures may ensue.</p> <p>Methods</p> <p>In the present study, alterations of the general GABA, GABA_Aand GABA_Breceptors in the cerebral cortex of the epileptic rat and the therapeutic application of <it>Bacopa monnieri </it>were investigated.</p> <p>Results</p> <p>Scatchard analysis of [³H]GABA, [³H]bicuculline and [³H]baclofen in the cerebral cortex of the epileptic rat showed significant decrease in B_max(P < 0.001) compared to control. Real Time PCR amplification of GABA receptor subunits such as GABA_Aά1, GABA_Aγ, GABA_Aδ, GABA_Band GAD where down regulated (P < 0.001) in epileptic rats. GABA_Aά5subunit and Cyclic AMP responsible element binding protein were up regulated. Confocal imaging study confirmed the decreased GABA receptors in epileptic rats. Epileptic rats have deficit in radial arm and Y maze performance.</p> <p>Conclusions</p> <p><it>Bacopa monnieri </it>and Bacoside-A treatment reverses epilepsy associated changes to near control suggesting that decreased GABA receptors in the cerebral cortex have an important role in epileptic occurrence; <it>Bacopa monnieri </it>and Bacoside-A have therapeutic application in epilepsy management.</p

Reproduction and metamorphosis in the Myristica Swamp tree frog, Mercurana myristicapalustris (Anura: Rhacophoridae)

This work is licensed under a Creative Commons Attribution 4.0 International License.The reproductive biology of the Myristica Swamp tree frog (Mercurana myristicapalustris), a monotypic rhacophorid frog endemic to the foothills of the Western Ghats mountains of India, has remained unknown since the description of the genus and species. We monitored individuals from parental generation amplexus to the completion of offspring generation tadpole metamorphosis. Surprisingly, our observations revealed that this species exhibits many previously unknown characteristics, including the first ever record of the female, and a diverse call repertoire, consisting of five different call types (the functions of which remain incompletely known). We were also able to determine that reproductive activity peaked during the late pre-monsoon season, that males engaged in intraspecific aggressive encounters to occupy and to defend desirable territories, and that oviposition took place in terrestrial nests made by females. Embryonic development in the unattended nest was followed by tadpole development, which concluded within 40 days. The specific breeding mode employed by Mercurana, which restricts its range to the endangered Myristica swamp ecosystem, likely renders it susceptible to multiple threats, which should be considered jointly in future conservation planning

Alterations in hippocampal serotonergic and INSR function in streptozotocin induced diabetic rats exposed to stress: neuroprotective role of pyridoxine and Aegle marmelose

Diabetes and stress stimulate hippocampal 5-HT synthesis, metabolism and release. The present study was carried out to find the effects of insulin, Aegle marmelose alone and in combination with pyridoxine on the hippocampal 5-HT, 5-HT2A receptor subtype, gene expression studies on 5-HT2A, 5-HTT, INSR, immunohistochemical studies and elevated plus maze in streptozotocin induced diabetic rats. 5-HT content showed a significant decrease (p < 0.001) and a significant increase (p < 0.001) in 5-HIAA in hippocampus of diabetic rats compared to control. 5-HT receptor binding parameters Bmax and Kd showed a significant decrease (p < 0.001) whereas 5-HT2A receptor binding parameters Bmax showed a significant decrease (p < 0.001) with a significant increase (p < 0.05) in Kd in hippocampus of diabetic rats compared to control. Gene expression studies of 5-HT2A, 5-HTT and INSR in hippocampus showed a significant down regulation (p < 0.001) in diabetic rats compared to control. Pyridoxine treated in combination with insulin and A. marmelose to diabetic rats reversed the 5-HT content, Bmax , Kd of 5-HT, 5-HT2A and gene expression of 5-HT2A, 5-HTT and INSR in hippocampus to near control. The gene expression of 5-HT2A and 5-HTT were confirmed by immunohistochemical studies. Behavioural studies using elevated plus maze showed that serotonin through its transporter significantly increased (p < 0.001) anxiety-related traits in diabetic rats which were corrected by combination therapy. Our results suggest that pyridoxine treated in combination with insulin and A. marmelose has a role in the regulation of insulin synthesis and release, normalising diabetic related stress and anxiety through hippocampal serotonergic function. This has clinical significance in the management of diabetes

Reproduction and metamorphosis in the Myristica Swamp tree frog, Mercurana myristicapalustris (Anura: Rhacophoridae)

The reproductive biology of the Myristica Swamp tree frog (Mercurana myristicapalustris), a monotypic rhacophorid frog endemic to the foothills of the Western Ghats mountains of India, has remained unknown since the description of the genus and species. We monitored individuals from parental generation amplexus to the completion of offspring generation tadpole metamorphosis. Surprisingly, our observations revealed that this species exhibits many previously unknown characteristics, including the first ever record of the female, and a diverse call repertoire, consisting of five different call types (the functions of which remain incompletely known). We were also able to determine that reproductive activity peaked during the late pre-monsoon season, that males engaged in intraspecific aggressive encounters to occupy and to defend desirable territories, and that oviposition took place in terrestrial nests made by females. Embryonic development in the unattended nest was followed by tadpole development, which concluded within 40 days. The specific breeding mode employed by Mercurana, which restricts its range to the endangered Myristica swamp ecosystem, likely renders it susceptible to multiple threats, which should be considered jointly in future conservation planning

GSK3β inhibition blocks melanoma cell/host interactions by downregulating N-cadherin expression and decreasing FAK phosphorylation.

This study addresses the role of glycogen synthase kinase (GSK)-3β signaling in the tumorigenic behavior of melanoma. Immunohistochemical staining revealed GSK3β to be focally expressed in the invasive portions of 12 and 33% of primary and metastatic melanomas, respectively. GSK3 inhibitors and small interfering RNA (siRNA) knockdown of GSK3β were found to inhibit the motile behavior of melanoma cells in scratch wound, three-dimensional collagen-implanted spheroid, and modified Boyden chamber assays. Functionally, inhibition of GSK3β signaling was found to suppress N-cadherin expression at the messenger RNA and protein levels, and was associated with decreased expression of the transcription factor Slug. Pharmacological and genetic ablation of GSK3β signaling inhibited the adhesion of melanoma cells to both endothelial cells and fibroblasts and prevented transendothelial migration, an effect rescued by the forced overexpression of N-cadherin. A further role for GSK3β signaling in invasion was suggested by the ability of GSK3β inhibitors and siRNA knockdown to block phosphorylation of focal adhesion kinase (FAK) and increase the size of focal adhesions. In summary, we have, to our knowledge, demonstrated a previously unreported role for GSK3β in modulating the motile and invasive behavior of melanoma cells through N-cadherin and FAK. These studies suggest the potential therapeutic utility of inhibiting GSK3β in defined subsets of melanoma

Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data

Abstract: Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers

A Study into the Use of Artificial Intelligence in E-Commerce Stock Management and Product Suggestion Generation for End Users

&lt;p&gt;&lt;em&gt;Abstract&lt;/em&gt;&mdash; Electronic commerce (E-commerce) has revolutionized the way people shop and interact with online customer service. Despite the fact that organizations are working to improve their customer service performance, traditional customer service issues such as limited availability, inefficiency, and cost continue to exist. Artificial intelligence, or AI, as these letters are known, is now found everywhere, including in e-commerce. Artificial intelligence (AI) is increasingly being used in service today to act as a human assistant to overcome the limitations of traditional customer service. AI and service providers can collaborate to provide perfect customer service while also increasing productivity. Choosing the right product will assist the user in getting what they want. This increases the user&#39;s satisfaction with the website.&lt;/p&gt; &lt;p&gt;To achieve a pleasant outcome, a website such as building a personal computer needs to add to the website. Suggestions for high-quality products for your computer aid in the optimization of the computer&#39;s speed and performance. At the same time, technological advancements have given rise to a variety of platforms that can be used to keep up with trends and meet market demands. As a result, the focus of this research is on the applications of artificial intelligence in the e-commerce industry. The AI assists the user in getting what they want and keeping up with the latest trends.&lt;/p&gt

Eflects of Bacopa monnieri and Bacoside A

The research work which was carried out to characterization of wastes from natural rubber and rubber wood processing industries and their utilization for biomethanation. Environmental contamination is an inevitable consequence of human activity. The liquid and solid wastes from natural rubber based industries were: characterized and their use for the production of biogas investigated with a view to conserve conventional energy, and to mitigate environmental degradation.Rubber tree (flevea brasiliensis Muell. Arg.), is the most important commercial source of natural rubber and in india. Recently, pollution from the rubber processing factories has become very serious due to the introduction of modern methods and centralized group processing practices.The possibility of the use of spent slurry as organic manure is discussed.l0 percent level of PSD, the activity of cellulolytic, acid producing,proteolytic, lipolytic and methanogenic bacteria were more in the middle stage of methanogenesis.the liquid wastes from rubber processing used as diluents in combination with PSD, SPE promoted more biogas production with high methane content in the gas.The factors that favour methane production like TS, VS, cellulose and hemicellulose degradation were favoured in this treatment which led to higher methane biogenesis.The results further highlight ways and means to use agricultural wastes as alternative sources of energy.Cochin University of Science and TechnologyDepartment of Biotechnology, Cochin University of Science and Technolog

Impact of COVID-19 Lockdown on Ambient Air Quality in the Southwest Coastal Urban Regions of India

The rapid growth of urban areas and population as well as associated development over recent decades have been a major factor controlling ambient air quality of the urban environment in Kerala (India). Being located at the southwestern fringe of the Indian peninsula, Kerala is one of the regions that has been significantly influenced by the activities in the Indian Ocean. The present study focuses on the effect of the COVID-19 lockdown (in 2021) on ambient air quality in the selected coastal metropolitan areas of Kerala. Although previous research studies reported improvement in ambient air quality in Kerala during the lockdown period, this study demonstrates the potential of onshore transport of air pollutants in controlling the air quality of coastal urban regions during the lockdown period. Data from the ambient air quality monitoring stations of the Kerala State Pollution Control Board in the urban areas of Thiruvananthapuram (TM), Kollam (KL), Kozhikode (KZ), and Kannur (KN) are used for the analysis. Temporal variation in the concentration of air pollutants during the pre-lockdown (PRLD), lockdown (LD), and post-lockdown (PTLD) periods (i.e., 1 March to 31 July) of 2021 is examined to assess the effect of lockdown measures on the National Air Quality Index (AQI). Results indicate a significant decline in the levels of air pollutants and subsequent improvement in air quality in the coastal urban areas. All the effect of lockdown measures has been evident in the AQI, an increase in the concentration of different pollutants including CO, SO2, and NH3 during the LD period suggests contributions from multiple sources including onshore transport due to marine traffic and transboundary transport