Therapeutic roles for carbon monoxide in subarachnoid hemorrhage

Approximately 1 in 10,000 North Americans have an aneurysmal subarachnoid hemorrhage (aSAH) each year. It is a devastating disease with a combined morbidity and mortality greater than 50%. Subarachnoid hemorrhage (SAH) can lead to neuronal injury and can impair cognitive function by increasing pressure on the brain. For these reasons, it is crucial that effective therapies for patients suffering from SAH are found. This thesis will discuss the clinical characteristics of SAH, as well as possible targets for therapeutic intervention. Carbon monoxide (CO) is commonly known as an environmental pollutant and toxic diatomic gas, infamous for its extremely high affinity for hemoglobin. Research has shown that CO possesses many of the same functions of nitric oxide. These functions include vasodilation, inhibition of platelet aggregation, and anti-proliferative effects on smooth muscle. It is also known as an anti-inflammatory agent under specific concentrations and conditions. Heme oxygenase isozymes (HO-1 and HO-2) both generate CO in the brain following ischemic injury. In ischemic stroke, the function of CO is mediated by upregulation of Nuclear factor-erythroid 2-related factor 2 (Nrf2). Nrf2 plays a protective role in a variety of neurological and inflammatory disorders. Experiments have shown that exogenous CO administered to mice with middle cerebral artery occlusions results in smaller infarct sizes in the brain compared to mice without CO treatment. CO treatment was most effective in its protective role after a 1-hour delay in treatment versus a 3-hour delay. Thus, a therapeutic window of time in which CO treatment in ischemic stroke is most effective needs to be elucidated. The same is true for hemorrhagic stroke. The evidence suggests that CO could have a neuroprotective effect following subarachnoid hemorrhage by decreasing cerebral inflammation

Institutional Credit through Cooperatives in Maharashtra: A Region-wise Analysis

In the era of financial sector reforms, sustainability, viability and operational efficiency of rural financial institutions (RFIs) are the major issues that need to be taken cognizance of in ensuring effective rural credit delivery system. However, the major problems plaguing the efficiency of rural credit delivery system are the mounting overdue and Non Performing Assets (NPAs) of RFIs. In the state of Maharashtra, the credit cooperatives have not only shown slower growth in their institutional finance coupled with much slower growth in their membership but also faster growth in outstanding loans as against their loan advances during the reform period. The reason for this dismal scenario can be associated with adverse environment created by the financial sector reforms, which have reduced the entire rural credit delivery through cooperatives to a moribund state. The financial sector reforms have accorded greater flexibility to cooperatives to invest in non-target avenues like shares and debentures of corporates, units of mutual funds, bonds of public sector undertakings, etc. This has affected credit flow from these major institutions operating in rural Maharashtra as most of their loans meant for farm finance are diverted to investments. The estimates of this study also show not only wide variation in total and crop loan advances of PACS but also their outstanding loans, overdue and per member borrowing across different regions of Maharashtra. The outstanding loan of PACS based on per hectare GCA is seen to have exceeded loan advances with a comfortable margin in all the regions of the state. Although increase in outstanding loan with rise in loan advances and GCA is another issue, the most important one among all is the mounting overdue and NPAs of cooperatives that sets a path where from there is no return and, which ultimately leads to inefficiency in cooperative credit delivery. In order to rejuvenate rural credit delivery system through cooperatives, the major problems facing the system, viz., high transaction cost, poor repayment performance, mounting NPAs, distributional aspect of credit, coverage of various social groups, etc., need to be tackled with more fiscal jurisprudence reserving exemplary punishment for willful defaults, particularly large farmers. In fact, insofar as the rural credit delivery system is concerned, the focus should be on strategies that are required for tackling issues such as sustainability and viability, operational efficiency, recovery performance, small farmer coverage and balanced sectoral development.Cooperative Credit Region-wise Analysis

Institutional Credit through Cooperatives in Maharashtra: A Region-wise Analysis

In the era of financial sector reforms, sustainability, viability and operational efficiency of rural financial institutions (RFIs) are the major issues that need to be taken cognizance of in ensuring effective rural credit delivery system. However, the major problems plaguing the efficiency of rural credit delivery system are the mounting overdue and Non Performing Assets (NPAs) of RFIs. In the state of Maharashtra, the credit cooperatives have not only shown slower growth in their institutional finance coupled with much slower growth in their membership but also faster growth in outstanding loans as against their loan advances during the reform period. The reason for this dismal scenario can be associated with adverse environment created by the financial sector reforms, which have reduced the entire rural credit delivery through cooperatives to a moribund state. The financial sector reforms have accorded greater flexibility to cooperatives to invest in non-target avenues like shares and debentures of corporates, units of mutual funds, bonds of public sector undertakings, etc. This has affected credit flow from these major institutions operating in rural Maharashtra as most of their loans meant for farm finance are diverted to investments. The estimates of this study also show not only wide variation in total and crop loan advances of PACS but also their outstanding loans, overdue and per member borrowing across different regions of Maharashtra. The outstanding loan of PACS based on per hectare GCA is seen to have exceeded loan advances with a comfortable margin in all the regions of the state. Although increase in outstanding loan with rise in loan advances and GCA is another issue, the most important one among all is the mounting overdue and NPAs of cooperatives that sets a path where from there is no return and, which ultimately leads to inefficiency in cooperative credit delivery. In order to rejuvenate rural credit delivery system through cooperatives, the major problems facing the system, viz., high transaction cost, poor repayment performance, mounting NPAs, distributional aspect of credit, coverage of various social groups, etc., need to be tackled with more fiscal jurisprudence reserving exemplary punishment for willful defaults, particularly large farmers. In fact, insofar as the rural credit delivery system is concerned, the focus should be on strategies that are required for tackling issues such as sustainability and viability, operational efficiency, recovery performance, small farmer coverage and balanced sectoral development.Institutional Credit Cooperatives Region-wise Analysis

Differential Regulation of the Period Genes in Striatal Regions following Cocaine Exposure

Several studies have suggested that disruptions in circadian rhythms contribute to the pathophysiology of multiple psychiatric diseases, including drug addiction. In fact, a number of the genes involved in the regulation of circadian rhythms are also involved in modulating the reward value for drugs of abuse, like cocaine. Thus, we wanted to determine the effects of chronic cocaine on the expression of several circadian genes in the Nucleus Accumbens (NAc) and Caudate Putamen (CP), regions of the brain known to be involved in the behavioral responses to drugs of abuse. Moreover, we wanted to explore the mechanism by which these genes are regulated following cocaine exposure. Here we find that after repeated cocaine exposure, expression of the Period (Per) genes and Neuronal PAS Domain Protein 2 (Npas2) are elevated, in a somewhat regionally selective fashion. Moreover, NPAS2 (but not CLOCK (Circadian Locomotor Output Cycles Kaput)) protein binding at Per gene promoters was enhanced following cocaine treatment. Mice lacking a functional Npas2 gene failed to exhibit any induction of Per gene expression after cocaine, suggesting that NPAS2 is necessary for this cocaine-induced regulation. Examination of Per gene and Npas2 expression over twenty-four hours identified changes in diurnal rhythmicity of these genes following chronic cocaine, which were regionally specific. Taken together, these studies point to selective disruptions in Per gene rhythmicity in striatial regions following chronic cocaine treatment, which are mediated primarily by NPAS2. © 2013 Falcon et al

Charged Dust Particles in Interplanetary Space

Charged dust particles in interplanetary spac

Resolving Non-performing Assets of the Indian Banking System

This paper reviews the nature of non-performing assets in the Indian banking system and discusses the key design features that would be important for the Asset Reconstruction Companies to play an effective role in resolving such non-performing assets.

Solution structure of a repeated unit of the ABA-1 nematode polyprotein allergen of ascaris reveals a novel fold and two discrete lipid-binding sites

Parasitic nematode worms cause serious health problems in humans and other animals. They can induce allergic-type immune responses, which can be harmful but may at the same time protect against the infections. Allergens are proteins that trigger allergic reactions and these parasites produce a type that is confined to nematodes, the nematode polyprotein allergens (NPAs). These are synthesized as large precursor proteins comprising repeating units of similar amino acid sequence that are subsequently cleaved into multiple copies of the allergen protein. NPAs bind small lipids such as fatty acids and retinol (Vitamin A) and probably transport these sensitive and insoluble compounds between the tissues of the worms. Nematodes cannot synthesize these lipids, so NPAs may also be crucial for extracting nutrients from their hosts. They may also be involved in altering immune responses by controlling the lipids by which the immune and inflammatory cells communicate. We describe the molecular structure of one unit of an NPA, the well-known ABA-1 allergen of Ascaris and find its structure to be of a type not previously found for lipid-binding proteins, and we describe the unusual sites where lipids bind within this structur

Cronobiología de la regulación metabólica

El organismo, a pesar de presentar una aparente continuidad, se regula siguiendo una serie de ciclos circadianos que ocurren de coordinadamente entre los distintos procesos que ocurren en los órganos y células. Ello se hace posible gracias a la existencia de los llamados “genes reloj” orquestados por el núcleo supraquiasmático (SCN), el cual adapta los procesos externos como el ciclo de luz/oscuridad con los internos. Estos genes se co-expresan en la práctica totalidad de los tejidos, y sus productos interactúan recíprocamente a nivel translacional y transcripcional para generar oscilaciones mediante una serie de ciclos de retroalimentación. Además, existen un conjunto de procesos post-traduccionales que hacen que estos ciclos circadianos sean posibles, gracias a una serie de moléculas como la nicotinamida difosfato (NAD+ ), las kinasas dependientes de AMP (AMPK) o el grupo hemo, que participan en dichos procesos interactuando de diferentes maneras con algunos de los genes reloj. Los procesos regulados por estos genes y moléculas incluyen el mantenimiento de los niveles de macronutrientes en plasma, así como su síntesis y destrucción de manera coordinada; la bioenergética mitocondrial, la presencia de un tipo de célula inmunitaria o los síntomas de algunas enfermedades. La desregulación de estos procesos puede conllevar a una ruptura de la homeostasis en el organismo y al padecimiento de enfermedades como obesidad, aterogénesis o síndrome metabólico, y por ello se hace de vital importancia conocer el funcionamiento de estos para evitar cualquier alteración

Issues And Challenges Faced by Small Finance Banks in Debt Collection with Special Reference to Rural Areas - A Conceptual Study

The Reserve Bank of India (RBI) created Small Finance Banks (SFBs) in 2015 to encourage financial inclusion and offer banking services to underserved populations. Small business units, micro- and small businesses, farmers, and low-income households are just a few examples of the unbanked and underbanked groups of the population that SFBs primarily target with basic banking services. SFBs are nevertheless vulnerable to non-performing assets (NPAs), which can arise for a number of causes, just like other banks. SFBs use a variety of strategies, such as effective credit appraisal and monitoring, quick recovery actions, loan restructuring, and legal action against defaulters, to manage and reduce their NPA levels. To maintain compliance with prudential norms and protect stability, the RBI supervises and conducts routine inspections of SFBs. &nbsp