Impact of HPV strains on molecular mechanisms of cervix cancer.

PURPOSE: Cervical cancer accounts for a high number of deaths worldwide. Risk factors are extensive for cervix cancer but Human papillomavirus (HPV) plays a prime role in its development. Different strains of HPV are prevalent globally, which show different grades of mortality and morbidity among women. This study is planned to evaluate the molecular mechanism of different strains of HPV infection and progression leading to cervix cancer. METHODS: This review includes different research articles on cervix cancer progression reported from India and all over the world. RESULTS: HPV 16 and 18 are prevalent strains using heparan sulfate-independent and dependent pathways for viral replication inside the cell. It also uses transcription mechanisms through NF-kappa B, FOXA-1, and AP-1 genes while strains like HPV-35, 45, and 52 are also predominant in India, which showed a very slow mechanism of progression due to which mortality rate is low after their infection with these strains. CONCLUSION: HPV uses E6 and E7 proteins which activate NF-kappa B and AP-1 pathway which suppresses the tumor suppressor gene and activates cytokine production, causing inflammation and leading to a decrease in apoptosis due to Caspase-3 activation. In contrast, the E7 protein involves HOXA genes and decreases apoptotic factors due to which mortality and incidence rates are low in viruses that use E7 motifs. Some HPV strains employ the cap-dependent pathway, which is also associated with lower mortality and infection rates.

FLRT2 and FLRT3 Cooperate in Maintaining the Tangential Migratory Streams of Cortical Interneurons during Development.

Neuron migration is a hallmark of nervous system development that allows gathering of neurons from different origins for assembling of functional neuronal circuits. Cortical inhibitory interneurons arise in the ventral telencephalon and migrate tangentially forming three transient migratory streams in the cortex before reaching the final laminar destination. Although migration defects lead to the disruption of inhibitory circuits and are linked to aspects of psychiatric disorders such as autism and schizophrenia, the molecular mechanisms controlling cortical interneuron development and final layer positioning are incompletely understood. Here, we show that mouse embryos with a double deletion of FLRT2 and FLRT3 genes encoding cell adhesion molecules exhibit an abnormal distribution of interneurons within the streams during development, which in turn, affect the layering of somatostatin+ interneurons postnatally. Mechanistically, FLRT2 and FLRT3 proteins act in a noncell-autonomous manner, possibly through a repulsive mechanism. In support of such a conclusion, double knockouts deficient in the repulsive receptors for FLRTs, Unc5B and Unc5D, also display interneuron defects during development, similar to the FLRT2/FLRT3 mutants. Moreover, FLRT proteins are chemorepellent ligands for developing interneurons in vitro, an effect that is in part dependent on FLRT-Unc5 interaction. Together, we propose that FLRTs act through Unc5 receptors to control cortical interneuron distribution in a mechanism that involves cell repulsion.SIGNIFICANCE STATEMENT Disruption of inhibitory cortical circuits is responsible for some aspects of psychiatric disorders such as schizophrenia or autism. These defects include interneuron migration during development. A crucial step during this process is the formation of three transient migratory streams within the developing cortex that determine the timing of interneuron final positioning and the formation of functional cortical circuits in the adult. We report that FLRT proteins are required for the proper distribution of interneurons within the cortical migratory streams and for the final laminar allocation in the postnatal cortex. These results expand the multifunctional role of FLRTs during nervous system development in addition to the role of FLRTs in axon guidance and the migration of excitatory cortical neurons.

Combined Interaction of Cellular and Extracellular Components Causes Genetic Cascade Activation in Breast Cancer Metastasis.

Breast cancer (BC) consists of malignant cells as well as surrounding nonmalignant cells - fibroblasts, macrophages, endothelial cells, lymphocytes, neutrophils, mesenchymal stem cells, and extracellular matrix (ECM). This surrounding stroma is referred to as the breast tumor microenvironment (BTME). The components of BTME interact with cancerous breast cells for the promotion of BC. The reciprocal cross talk between BTME and neoplastic breast cells, through the secretion of chemicals, growth factors, and chemokines, may lead to cell proliferation, migration, metastasis as well as immune response suppression. Multiple genetic loci, in association with stromal components, are linked to immunological stimuli to induce BC in ductal cells. These genes participate in tumor activation pathways and promote carcinogenesis via fibroblast, leukocyte, and endothelial-cell-mediated responses. The collaborative effect of the cellular components and BTME-associated genes plays vital role in tumor initiation and metastasis of breast cells. This process involves genes which cause degenerative changes in ECM leading to epithelial-mesenchymal transitions, which finally causes metastatic BC. This shows that metastatic BC results from combined activation of different cellular and extracellular components, and their activity is primarily controlled by activation of the genetic cascade. These components work simultaneously to cause metastatic BC.

Climate change water vulnerability and adaptation mechanism in a Himalayan City, Nainital, India.

Urban water management is a growing concern in India's rapidly urbanizing cities. Population growth and climatic variability are exuberating the impact on surface and underground water supply. Understanding the causes and the extent of water vulnerability is required for developing effective strategies for water insecurities. This study attempts to assess the water vulnerability across different wards of a touristic city of Himalaya-Nainital using IPCC approach considering the three dimensions: exposure, sensitivity, and adaptive capacity. Seven indicators, mostly spatial, i.e. edaphic (aspect, elevation) and climatic (land surface temperature) besides some water infrastructural (distance to water distribution) and population, were considered for development of vulnerability index using Analytical Hierarchy Process for assigning weights. These indicators were simple to extract and easy to obtain and mostly available from secondary sources and were capable to account the variability at micro-level. Moreover, the current adaptation mechanisms for water security were also derived through conducting surveys by randomly selecting households across the wards. Staff House and Harinagar wards were the most vulnerable. The survey results that the adaptation mechanism should be managed at individual and organization level. Policy measures such as optimum use of water, grey water recycling, spring rejuvenation, rain water harvesting, and leakage proof infrastructure with intervention of new technologies, may be adopted and implemented for reducing the water vulnerability in the city along with the public participation. The appropriate measures for water vulnerability would further provide support for improving the facilities to the tourists in the city thereby improved economic opportunities to the locals.

Down-regulation of RdRp complex and activated immune response due to increased arsenic level leads to decreased corona virus replication.

Corona virus is pandemic and responsible for more than 5.6 million deaths. It was observed that its severity was reported in varied ways in different countries and even in different states of India. This variation was critically evaluated in the area with high contamination of Arsenic (As) to understand the arsenic toxicity and Covid epidemiology and associated health effects in the human population. It was reported that the area with low arsenic contamination has a very high incidence rate of Corona infection in the world. Even in the Indian scenario, high As-contaminated states like West Bengal, Jharkhand and Bihar, the incidence rate is 1.994%, 1.114% and 0.661%, respectively. In contrast, states with the least arsenic contamination have a very high corona incidence rate like 6.308, 17.289 and 4.351, respectively. It was evident that Arsenic inhibits the RdRp complex, which leads to the inhibition of viral genome replication. The PAMP associated pathway was activated by Arsenic and effectively bound with viral spike proteins leading to effective clearance of virus through activation of TNF alpha and IL-1. It finally leads to increased production of IgE, IgG and IGA. Arsenic also enhances inflammatory response against the virus through increased production of cytokine. The high arsenic level also induces apoptosis in viral infected cells through Bax/Bak pathway. It activates cytochrome-c and caspase-3 activity, inducing apoptosis in viral infected cells through PARP activation in the nucleus. These combined findings suggest that high arsenic contamination causes replication inhibition, activates an inflammatory response, increases antibody production, and finally leads to apoptosis through the mitochondrial pathway. People residing in arsenic hit areas are at a very low threat of corona infection.