45 research outputs found
Pulin B. Nayak, Economic Development of India
No full textAbstract. The paradigm shift in economic policy in the 1990s elicited a tremendous interest in the pace and pattern of economic development of India. Indian economic policies as also the process of her development is being closely monitored and written about by academics, global institutions, think tanks, media, political analysts and civil society within and outside the country. The development issues of erstwhile British colonies did not attract adequate academic attention for the most part of the twentieth century. A four volume compendium of 75 papers giving a comprehensive account of the development process of the Indian economy by Pulin Nayak is a timely and valuable contribution to the pool of studies being carried out on India in different parts of the globe. Introduction to the four volume book reflects the scholarship of the author, which will be of immense academic value to anyone who is interested in the historical backdrop of the development path chosen by the Indian leaders after Independence of the country in 1947. It builds on the discourse of development economics for low income countries.Keywords. Economic Development, Indian economy.JEL. F60, F63, I15, I25, N01, O00, O10
Identification of claudin-1 as an entry factor in dengue infection and development of a high throughput screening assay for antivirals against dengue virus
No full textDengue virus (DENV) has become a huge public health concern around the world with no vaccine or antivirals available. More than one-third of the world\u27s population is living in areas at risk of infection. To conquer the dengue disease, a better understanding of virus-host interactions and development of the appropriate therapeutic treatments are required. In this dissertation, we first broadly reviewed the factors involved in dengue viral entry and the role of tight junctions as a pathogen target. Second, we developed, optimized and validated a high throughput screening (HTS) assay for anti-dengue virus drug screening. Taking advantage of using live virus, this assay is able to examine the effects of both viral and host factors throughout the whole viral life cycle. Viral entry, the first step of the dengue lifecycle, provides attractive therapeutic targets. Although various factors have been described as playing a role in dengue virus entry, little is known about the initial virus attachment and binding. Thus, in an effort to obtain better understanding of virus-host interactions involved in the early stage of dengue infection, this screening assay was used to evaluate potential host factors. In the third part, we specifically described and characterized claudin-1 as a potential entry factor required for efficient dengue entry. Briefly, we showed that dengue entry was hampered in claudin-1 depleted cells, resulting in delayed development of cytopathology and decreased progeny virus production. This was further evidenced by rescued dengue entry in cells with restored claudin-1 expression. Functional analysis using recombinant claudin-1 mutants revealed a direct interaction with the viral prM protein. Collectively, these studies suggested a role of claudin-1 in efficient DENV entry. In summary, this dissertation provides new insights into dengue virus-host interactions and, for the first time, provides evidence that tight junctions act as a pathogen target in dengue virus infection
Cumulative learning
No full textAn important feature of human learning is the ability to continuously accept new information and unify it with existing knowledge, a process that proceeds largely automatically and without catastrophic side-effects. A generally intelligent machine (AGI) should be able to learn a wide range of tasks in a variety of environments. Knowledge acquisition in partially-known and dynamic task-environments cannot happen all-at-once, and AGI-aspiring systems must thus be capable of cumulative learning: efficiently making use of existing knowledge while learning new things, increasing the scope of ability and knowledge incrementally—without catastrophic forgetting or damaging existing skills. Many aspects of such learning have been addressed in artificial intelligence (AI) research, but relatively few examples of cumulative learning have been demonstrated to date and no generally accepted explicit definition exists of this category of learning. Here we provide a general definition of cumulative learning and describe how it relates to other concepts frequently used in the AI literature.Information and Communication Technolog
The interaction between claudin-1 and dengue viral prM/M protein for its entry
No full textAbstractDengue disease is becoming a huge public health concern around the world as more than one-third of the world's population living in areas at risk of infection. In an effort to assess host factors interacting with dengue virus, we identified claudin-1, a major tight junction component, as an essential cell surface protein for dengue virus entry. When claudin-1 was knocked down in Huh 7.5 cells via shRNA, the amount of dengue virus entering host cells was reduced. Consequently, the progeny virus productions were decreased and dengue virus-induced CPE was prevented. Furthermore, restoring the expression of claudin-1 in the knockdown cells facilitated dengue virus entry. The interaction between claudin-1 and dengue viral prM protein was further demonstrated using the pull-down assay. Deletion of the extracellular loop 1 (ECL1) of claudin-1 abolished such interaction, so did point mutations C54A, C64A and I32M on ECL1. These results suggest that the interaction between viral protein prM and host protein claudin-1 was essential for dengue entry. Since host and viral factors involved in virus entry are promising therapeutic targets, determining the essential role of claudin-1 could lead to the discovery of entry inhibitors with attractive therapeutic potential against dengue disease
Validating a Firefly Luciferase-Based High-Throughput Screening Assay for Antimalarial Drug Discovery
No full textAge-dependent differential regulation of anxiety- and depression-related behaviors by neurabin and spinophilin
No full text© 2017 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Affective disorders impact nearly 10% of the adult population in the United States in a given year. Synaptic dysfunction has recently emerged as a key neurobiological mechanism underlying affective disorders such as anxiety and depression. In this study, we investigate the potential role of two synaptic scaffolding proteins, neurabin and spinophilin, in regulating anxiety- and depression-related behaviors at different ages using genetically deficient mice. Loss of the neurabin gene reduces anxiety-like behavior in the elevated zero maze in young adult mice (3–5 months old), but not in middle aged mice (11–13 months old), whereas loss of spinophilin decreases anxiety in middle-aged mice, but not in young adult mice. Neurabin knockout (KO) mice also show reduced immobility in the repeated force swim test (FST) at 3–5 months, but not 11–3 months, of age, compared to age- and strain-matched wild type (WT) controls. Conversely, spinophilin KO mice display a lower level of this behavioral despair than matched WT controls after repeated FST trials at the middle age (11–13 months) but not the young age (3–5 months). Together, these data indicate that, despite their structural similarities and overlapping function in regulating synaptic cytoskeleton, the two homologs neurabin and spinophilin play important yet distinct roles in the regulation of anxiety- and depression-like behaviors in an age-dependent manner. Our studies provide new insights into the complex neurobiology of affective disorders
Age-dependent differential regulation of anxiety- and depression-related behaviors by neurabin and spinophilin
No full textThe Role of <i>Pseudomonas aeruginosa</i> Virulence Factors in Cytoskeletal Dysregulation and Lung Barrier Dysfunction
No full textPseudomonas (P.) aeruginosa is an opportunistic pathogen that causes serious infections and hospital-acquired pneumonia in immunocompromised patients. P. aeruginosa accounts for up to 20% of all cases of hospital-acquired pneumonia, with an attributable mortality rate of ~30–40%. The poor clinical outcome of P. aeruginosa-induced pneumonia is ascribed to its ability to disrupt lung barrier integrity, leading to the development of lung edema and bacteremia. Airway epithelial and endothelial cells are important architecture blocks that protect the lung from invading pathogens. P. aeruginosa produces a number of virulence factors that can modulate barrier function, directly or indirectly, through exploiting cytoskeleton networks and intercellular junctional complexes in eukaryotic cells. This review summarizes the current knowledge on P. aeruginosa virulence factors, their effects on the regulation of the cytoskeletal network and associated components, and molecular mechanisms regulating barrier function in airway epithelial and endothelial cells. A better understanding of these processes will help to lay the foundation for new therapeutic approaches against P. aeruginosa-induced pneumonia
Age-dependent differential regulation of anxiety- and depression-related behaviors by neurabin and spinophilin.
No full textAffective disorders impact nearly 10% of the adult population in the United States in a given year. Synaptic dysfunction has recently emerged as a key neurobiological mechanism underlying affective disorders such as anxiety and depression. In this study, we investigate the potential role of two synaptic scaffolding proteins, neurabin and spinophilin, in regulating anxiety- and depression-related behaviors at different ages using genetically deficient mice. Loss of the neurabin gene reduces anxiety-like behavior in the elevated zero maze in young adult mice (3-5 months old), but not in middle aged mice (11-13 months old), whereas loss of spinophilin decreases anxiety in middle-aged mice, but not in young adult mice. Neurabin knockout (KO) mice also show reduced immobility in the repeated force swim test (FST) at 3-5 months, but not 11-3 months, of age, compared to age- and strain-matched wild type (WT) controls. Conversely, spinophilin KO mice display a lower level of this behavioral despair than matched WT controls after repeated FST trials at the middle age (11-13 months) but not the young age (3-5 months). Together, these data indicate that, despite their structural similarities and overlapping function in regulating synaptic cytoskeleton, the two homologs neurabin and spinophilin play important yet distinct roles in the regulation of anxiety- and depression-like behaviors in an age-dependent manner. Our studies provide new insights into the complex neurobiology of affective disorders
