Aldose Reductase Inhibition Prevents Metaplasia of Airway Epithelial Cells

BACKGROUND: Goblet cell metaplasia that causes mucus hypersecretion and obstruction in the airway lumen could be life threatening in asthma and chronic obstructive pulmonary disease patients. Inflammatory cytokines such as IL-13 mediate the transformation of airway ciliary epithelial cells to mucin-secreting goblet cells in acute as well as chronic airway inflammatory diseases. However, no effective and specific pharmacologic treatment is currently available. Here, we investigated the mechanisms by which aldose reductase (AR) regulates the mucus cell metaplasia in vitro and in vivo. METHODOLOGY/FINDINGS: Metaplasia in primary human small airway epithelial cells (SAEC) was induced by a Th2 cytokine, IL-13, without or with AR inhibitor, fidarestat. After 48 h of incubation with IL-13 a large number of SAEC were transformed into goblet cells as determined by periodic acid-schiff (PAS)-staining and immunohistochemistry using antibodies against Mucin5AC. Further, IL-13 significantly increased the expression of Mucin5AC at mRNA and protein levels. These changes were significantly prevented by treatment of the SAEC with AR inhibitor. AR inhibition also decreased IL-13-induced expression of Muc5AC, Muc5B, and SPDEF, and phosphorylation of JAK-1, ERK1/2 and STAT-6. In a mouse model of ragweed pollen extract (RWE)-induced allergic asthma treatment with fidarestat prevented the expression of IL-13, phosphorylation of STAT-6 and transformation of epithelial cells to goblet cells in the lung. Additionally, while the AR-null mice were resistant, wild-type mice showed goblet cell metaplasia after challenge with RWE. CONCLUSIONS: The results show that exposure of SAEC to IL-13 caused goblet cell metaplasia, which was significantly prevented by AR inhibition. Administration of fidarestat to mice prevented RWE-induced goblet cell metaplasia and AR null mice were largely resistant to allergen induced changes in the lung. Thus our results indicate that AR inhibitors such as fidarestat could be developed as therapeutic agents to prevent goblet cell metaplasia in asthma and related pathologies

Regional research priorities in brain and nervous system disorders

The characteristics of neurological, psychiatric, developmental and substance-use disorders in low-and middle-income countries are unique and the burden that they have will be different from country to country. Many of the differences are explained by the wide variation in population demographics and size, poverty, conflict, culture, land area and quality, and genetics. Neurological, psychiatric, developmental and substance-use disorders that result from, or are worsened by, a lack of adequate nutrition and infectious disease still afflict much of sub-Saharan Africa, although disorders related to increasing longevity, such as stroke, are on the rise. In the Middle East and North Africa, major depressive disorders and post-traumatic stress disorder are a primary concern because of the conflict-ridden environment. Consanguinity is a serious concern that leads to the high prevalence of recessive disorders in the Middle East and North Africa and possibly other regions. The burden of these disorders in Latin American and Asian countries largely surrounds stroke and vascular disease, dementia and lifestyle factors that are influenced by genetics. Although much knowledge has been gained over the past 10 years, the epidemiology of the conditions in low-and middle-income countries still needs more research. Prevention and treatments could be better informed with more longitudinal studies of risk factors. Challenges and opportunities for ameliorating nervous-system disorders can benefit from both local and regional research collaborations. The lack of resources and infrastructure for health-care and related research, both in terms of personnel and equipment, along with the stigma associated with the physical or behavioural manifestations of some disorders have hampered progress in understanding the disease burden and improving brain health. Individual countries, and regions within countries, have specific needs in terms of research priorities.Fil: Ravindranath, Vijayalakshmi. Indian Institute of Science; IndiaFil: Dang, Hoang Minh. Vietnam National University; VietnamFil: Goya, Rodolfo Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaFil: Mansour, Hader. University of Pittsburgh; Estados Unidos. Mansoura University; EgiptoFil: Nimgaonkar, Vishwajit L.. University of Pittsburgh; Estados UnidosFil: Russell, Vivienne Ann. University of Cape Town; SudáfricaFil: Xin, Yu. Peking University; Chin

Tree species diversity in a village ecosystem in Uttara Kannada district in Western Ghats, Karnataka

Cultivating trees in the agricultural systems is one of the major practices in the tropics of South and Southeast Asia1. It is characterized by an intensive integration of forest trees, agricultural and horticultural crops, and shrubs with a basic objective to ensure sustained availability of multiple products as direct benefits such as food, vegetables, fruits, fodder, fuel, foliage, medicine, and raw materials for agricultural implements. Other indirect benefits and services such as ornamentals, shading, live-fencing and shelter-belt or wind-breaks are also derived2. Such intermixing of species of agriculture and forestry, often termed as‘agroforestry’ came into international prominence as a potential source of solutions of many inter-related problems of production and conservation troubling land-use systems in the tropical and subtropical regions3. It has also been stated that the tree components along with field crops lead to efficient use of sunlight, moisture and nutrients in agro-ecosystems than in monocropping of either agricultural or forestry crops1. This kind of practice is more popular in Kerala, where home-gardens are built around coconut orchards4. Such home-gardens and agroforestry systems also prevail in humid tropics of the Western Ghats, Karnataka. However, there are no specific studies detailing the status of such systems in Karnataka, though a study on the use of tree biomass is available in the semi-arid zone of the state5,6

Swarm Intelligence Based Feature Selection for Intrusion and Detection System in Cloud Infrastructure

© 2020 IEEE. Network intrusion and cyber attacks are the most severe concern for Cloud computing service providers. The vulnerability of attacks is on a hike that manual or simple rule-based detection of cyber-attacks is not robust. In order to tackle cyber attacks in a reliable manner, an automated Intrusion Detection system equipped with a swarm intelligence (SI) based machine learning model (ML) is essential to deploy at entry points of the network. Nowadays, the application of SI with ML is used in various research areas. For an efficient IDS, choosing relevant features from the noisy data is an open question. In this regard, this paper proposes a method that utilizes the Whale Pearson hybrid feature selection wrapper for reducing the irrelevancy in the IDS model. Whale Pearson hybrid wrapper is an improved version of the binary Whale optimization Algorithm (WOA). The WOA is a type of SI algorithm which is inspired by the behavior of humpback whales. The proposed method has chosen 8 out of 42 features from the Hackereath Network attack prediction data-set, which are sufficient for building an efficient Intrusion detection model. The model trained with the eight features produces an accuracy of 80%, which is 8% greater than the accuracy produced by the original data-set with the KNN algorithm on ten-fold cross-validation

A comparative analysis of regeneration in natural forests and joint forest management plantations in Uttara Kannada district, Western Ghats

Five villages undertaking joint forest management (JFM) were chosen in Uttara Kannada district, Karnataka for assessing regeneration in plantations and nearby natural forests of the village. Species number, stem density, diversity index, similarity in species composition in less disturbed and disturbed forests and plantations in the village were compared. Stem density was low in all the disturbed forests; however, the species number was low in disturbed forests of three villages and high in two villages. Plantations showed lower diversity values compared to the adjacent natural forests. Regeneration in all less disturbed forests was better compared to the disturbed counterparts. Villages were ranked based on number of landless families, per, capita forest available and number of cut stems. Assessment of village forests using ranks indicates that parameters such as per capita availability, cut stems in the forests may determine the success of JFM

Effect of protection on regeneration in some selected village forestsunder community protection in Uttara Kannada district, Karnataka, India

Effect of protection on regeneration and species similarity was studied in six village forests under Joint Forest Management in Uttara Kannada district, the Western Ghats. Difference in species number, stem density, basal area of planted and natural species, and shrub density was compared between two observations in all the villages studied. All village forests experienced a decrease in the number of stems after the protection was withdrawn. The decrease in overall density of natural species was more (19.7%) than that of the exotic species (8.2%). This could be because of the utility of native species than the exotic ones.Basal area increased for stems that were planted, while it generally decreased for stems of natural species. The overall basal area,including native and planted species, had increased during the observation period indicating biomass accumulation. Shrub density increased in all villages except in Kadle, where there was no natural vegetation in the village forest. Greater similarity of species was found for planted species within the same village forests before and after protection. The number of cut stems increased significantly when the protection was removed, indicating diversion of pressure. The community did not prefer exotic species that were planted and on the other hand the native species were used to meet various biomass needs.The study indicates that the programme should develop strategies that incorporate various measures to conserve and maintain the village forests