GABAA and GABAB Receptor Gene Expression and Functional Regulation During Pancreatic Regeneration and Insulin Secretion in Rats

The present study demonstrate the functional alterations of the GABAA and GABAB receptors and the gene expression during the regeneration of pancreas following partial pancreatectomy. The role of these receptors in insulin secretion and pancreatic DNA synthesis using the specific agonists and antagonists also are studied in vitro. The alterations of GABAA and GABAR receptor function and gene expression in the brain stem, crebellum and hypothalamus play an important role in the sympathetic regulation of insulin secretion during pancreatic regeneration. Previous studies have given much information linking functional interaction between GABA and the peripheral nervous system. The involvement of specific receptor subtypes functional regulation during pancreatic regeneration has not given emphasis and research in this area seems to be scarce. We have observed a decreased GABA content, down regulation of GABAA receptors and an up regulation of GABAB receptors in the cerebral cortex, brain stem and hypothalamus. Real Time-PCR analysis confirmed the receptor data in the brain regions. These alterations in the GABAA and GABAB receptors of the brain are suggested to govern the regenerative response and growth regulation of the pancreas through sympathetic innervation. In addition, receptor binding studies and Real Time-PCR analysis revealed that during pancreatic regeneration GABAA receptors were down regulated and GABAB receptors were up regulated in pancreatic islets. This suggests an inhibitory role for GABAA receptors in islet cell proliferation i.e., the down regulation of this receptor facilitates proliferation. Insulin secretion study during 1 hour showed GABA has inhibited the insulin secretion in a dose dependent manner in normal and hyperglycaemic conditions. Bicuculline did not antagonize this effect. GABAA agonist, muscimol inhibited glucose stimulated insulin secretion from pancreatic islets except in the lowest concentration of 1O-9M in presence of 4mM glucose.Musclmol enhanced insulin secretion at 10-7 and 10-4M muscimol in presence of 20mM glucose- 4mM glucose represents normal and 20mM represent hyperglycaemic conditions. GABAB agonist, baclofen also inhibited glucose induced insulin secretion and enhanced at the concentration of 1O-5M at 4mM glucose and at 10-9M baclofen in presence of 20mM glucose. This shows a differential control of the GABAA and GABAB receptors over insulin release from the pancreatic islets. During 24 hours in vitro insulin secretion study it showed that low concentration of GABA has inhibited glucose stimulated insulin secretion from pancreatic islets. Muscimol, the GABAA agonist, inhibited the insulin secretion but, gave an enhanced secretion of insulin in presence of 4mM glucose at 10-7 , 10-5 and 1O-4M muscimol. But in presence of 20mM glucose muscimol significantly inhibited the insulin secretion. GABAB agonist, baclofen also inhibited glucose induced insulin secretion in presence of both 4mM and 20mM glucose. This shows the inhibitory role of GABA and its specific receptor subtypes over insulin synthesis from pancreatic bete-islets. In vitro DNA synthesis studies showed that activation of GABAA receptor by adding muscimol, a specific agonist, inhibited islet DNA synthesis. Also, the addition of baclofen, a specific agonist of GABAB receptor resulted in the stimulation of DNA synthesis.Thus the brain and pancreatic GABAA and GABAB receptor gene expression differentially regulates pancreatic insulin secretion and islet cell proliferation during pancreatic regeneration. This will have immense clinical significance in therapeutic applications in the management of Diabetes mellitus.

Glycogen degrading enzymes and their regulation in benthic animals and estuarine fish

Alpha glucan phosphorylase plays a very significant role in glycolysis. The inhibition and activation of this enzyme have significant effect on the rate of glycolysis. The rate of glycolysis is also determined by the interconversion between the active 3 and inactive Q forms of phosphorylase by two specific enzymes called phosphorylase phosphatase and phosphorylase kinase. The allosteric properties and interconversion mechanism reported for well—studied animal muscle phosphorylases do not fall under a general pattern. Studies using purified phosphorylase from marine sources are scanty. Detailed studies using specialised tissues from more marine animals are necessary to find the factors that control the properties and activities of the enzyme. This thesis is an attempt in this direction. The thesis deals with a detailed study of the control of the phosphorylase by both allosterism and interconversion between the g and b forms from four different aquatic animals of different habitat. Phosphorylase frm the four different animal muscles were purified either partially or completely and the kinetic and control properties were studied.

Nuclear organisation and epigenetic regulation of gene expression in Dictyostelium discoideum

A series of vectors for the over-expression of tagged proteins in Dictyostelium were designed, constructed and tested. These vectors allow the addition of an N- or C-terminal tag (GFP, RFP, 3xFLAG, 3xHA, 6xMYC and TAP) with an optimized polylinker sequence and no additional amino acid residues at the N or C terminus. Different selectable markers (Blasticidin and gentamicin) are available as well as an extra chromosomal version; these allow copy number and thus expression level to be controlled, as well as allowing for more options with regard to complementation, co- and super-transformation. Finally, the vectors share standardized cloning sites, allowing a gene of interest to be easily transfered between the different versions of the vectors as experimental requirements evolve. The organisation and dynamics of the Dictyostelium nucleus during the cell cycle was investigated. The centromeric histone H3 (CenH3) variant serves to target the kinetochore to the centromeres and thus ensures correct chromosome segregation during mitosis and meiosis. A number of Dictyostelium histone H3-domain containing proteins as GFP-tagged fusions were expressed and it was found that one of them functions as CenH3 in this species. Like CenH3 from some other species, Dictyostelium CenH3 has an extended N-terminal domain with no similarity to any other known proteins. The targeting domain, comprising α-helix 2 and loop 1 of the histone fold is required for targeting CenH3 to centromeres. Compared to the targeting domain of other known and putative CenH3 species, Dictyostelium CenH3 has a shorter loop 1 region. The localisation of a variety of histone modifications and histone modifying enzymes was examined. Using fluorescence in situ hybridisation (FISH) and CenH3 chromatin-immunoprecipitation (ChIP) it was shown that the six telocentric centromeres contain all of the DIRS-1 and most of the DDT-A and skipper transposons. During interphase the centromeres remain attached to the centrosome resulting in a single CenH3 cluster which also contains the putative histone H3K9 methyltransferase SuvA, H3K9me3 and HP1 (heterochromatin protein 1). Except for the centromere cluster and a number of small foci at the nuclear periphery opposite the centromeres, the rest of the nucleus is largely devoid of transposons and heterochromatin associated histone modifications. At least some of the small foci correspond to the distal telomeres, suggesting that the chromosomes are organised in a Rabl-like manner. It was found that in contrast to metazoans, loading of CenH3 onto Dictyostelium centromeres occurs in late G2 phase. Transformation of Dictyostelium with vectors carrying the G418 resistance cassette typically results in the vector integrating into the genome in one or a few tandem arrays of approximately a hundred copies. In contrast, plasmids containing a Blasticidin resistance cassette integrate as single or a few copies. The behaviour of transgenes in the nucleus was examined by FISH, and it was found that low copy transgenes show apparently random distribution within the nucleus, while transgenes with more than approximately 10 copies cluster at or immediately adjacent to the centromeres in interphase cells regardless of the actual integration site along the chromosome. During mitosis the transgenes show centromere-like behaviour, and ChIP experiments show that transgenes contain the heterochromatin marker H3K9me2 and the centromeric histone variant H3v1. This clustering, and centromere-like behaviour was not observed on extrachromosomal transgenes, nor on a line where the transgene had integrated into the extrachromosomal rDNA palindrome. This suggests that it is the repetitive nature of the transgenes that causes the centromere-like behaviour. A Dictyostelium homolog of DET1, a protein largely restricted to multicellular eukaryotes where it has a role in developmental regulation was identified. As in other species Dictyostelium DET1 is nuclear localised. In ChIP experiments DET1 was found to bind the promoters of a number of developmentally regulated loci. In contrast to other species where it is an essential protein, loss of DET1 is not lethal in Dictyostelium, although viability is greatly reduced. Loss of DET1 results in delayed and abnormal development with enlarged aggregation territories. Mutant slugs displayed apparent cell type patterning with a bias towards pre-stalk cell types.

Exploratory and dust-bathing behaviour in laying hens kept in commercial aviaries and furnished cages

The aim of the present thesis was to identify management factors that affect the extent of exploratory behaviour (ground pecking, scratching) as well as quantitative and qualitative as-pects of dust-bathing behaviour in laying hens kept in commercial furnished cages (‘small group housing’) and aviaries. Based on the results, it should be considered which management measures can be recommended for farmers to enhance hen welfare. The feasibility of direct observations of dust-bathing behaviour as well as video observations of exploratory and dust-bathing behaviour was tested in two aviaries. The direct observations were judged to be unfeasible under the conditions encountered. For the analysis of the video recordings, different sampling intervals for instantaneous scan sampling, different extents of observation time, and intra- and inter-observer reliabilities were compared and the most ap-propriate observation scheme selected. Applying the selected scheme (observing the first 16 minutes of every hour distributed over two consecutive light days with a sample interval of two minutes), within the range of environmental conditions found in 22 aviaries, pecking, scratching and dust-bathing behaviour was performed on average 25, 2 and 7 % of the obser-vation time. Hen numbers in the litter were positively associated with stocking density and group size. More scratching was performed with increasing litter height as well as in humid litter. If no litter had been provided, thus substrate consisted of dust and faeces, a reduced proportion of dust-bathing was found. The same method was then used in 16 furnished cage systems. On average 12 % of the total hen number were found on the scratching mats. The hens spent 8 % of the observed time pecking at the mat, 4 % dust-bathing and 0.4 % scratch-ing. Higher proportions were found on the mats and more dust-bathing behaviour occurred, if substrate was provided. Also with increasing light intensity and stocking density more hens were observed on the mats. More pecking and scratching occurred in conditions of higher stocking density, probably due to social facilitation, and of increased mat area per hen. With increasing mat numbers per cage less pecking was observed. Wider mats led to increased dust-bathing behaviour. Finally, 129 dust-baths recorded in 17 aviaries were analysed in detail. On average they lasted 17 minutes, with the tossing phase taking 69 % of this time, including on average 2 vertical wing shakes and 3 scratches with one leg per minute tossing phase. Dust-bath duration de-creased with increasing litter height. Litter type influenced all recorded parameters: dust-bath duration was highest on straw and lowest on fine material and fine material mixed with straw, where on both also the proportion of the tossing phase was lowest. The number of vertical wing shakes during the dust-bath was highest on straw and lowest on fine material mixed with straw as against the frequency of vertical wing shaking that was lowest on straw and highest on fine material. If dust-bathing hens were disturbed twice or more, dust-bathing duration decreased. With increasing light intensity a decreased proportion of the tossing phase as well as a reduced number of vertical wing shakes were recorded. Possibly the light stimulated the hens to dust-bath more often with less tossing behaviour per performance. The observed variation of the dust-bathing parameters could reflect successful adaptation or frustration of the hens. The litter and light conditions on the investigated farms were predominantly restrictive in terms of stimulation of exploration and dust-bathing behaviour. Thus, it was only possible to analyse possible associations between these factors and exploration and dust-bathing behav-iour within the range found. Based on the results the following management recommendations can be given: To allow hens in furnished cages more normal activity, substrate availability should be improved and mat space and light intensity increased. With regard to aviaries as well litter availability should be improved. Litter height should not be too low. Disturbances during dust-bathing should be prevented, but no influencing factors could be identified.

From evolution to co-evolution – An empirical study of the role of innovation, policy and public research in industrial dynamics

In the past decades since Schumpeter’s influential writings economists have pursued research to examine the role of innovation in certain industries on firm as well as on industry level. Researchers describe innovations as the main trigger of industry dynamics, while policy makers argue that research and education are directly linked to economic growth and welfare. Thus, research and education are an important objective of public policy. Firms and public research are regarded as the main actors which are relevant for the creation of new knowledge. This knowledge is finally brought to the market through innovations. What is more, policy makers support innovations. Both actors, i.e. policy makers and researchers, agree that innovation plays a central role but researchers still neglect the role that public policy plays in the field of industrial dynamics. Therefore, the main objective of this work is to learn more about the interdependencies of innovation, policy and public research in industrial dynamics. The overarching research question of this dissertation asks whether it is possible to analyze patterns of industry evolution – from evolution to co-evolution – based on empirical studies of the role of innovation, policy and public research in industrial dynamics. This work starts with a hypothesis-based investigation of traditional approaches of industrial dynamics. Namely, the testing of a basic assumption of the core models of industrial dynamics and the analysis of the evolutionary patterns – though with an industry which is driven by public policy as example. Subsequently it moves to a more explorative approach, investigating co-evolutionary processes. The underlying questions of the research include the following: Do large firms have an advantage because of their size which is attributable to cost spreading? Do firms that plan to grow have more innovations? What role does public policy play for the evolutionary patterns of an industry? Are the same evolutionary patterns observable as those described in the ILC theories? And is it possible to observe regional co-evolutionary processes of science, innovation and industry evolution? Based on two different empirical contexts – namely the laser and the photovoltaic industry – this dissertation tries to answer these questions and combines an evolutionary approach with a co-evolutionary approach. The first chapter starts with an introduction of the topic and the fields this dissertation is based on. The second chapter provides a new test of the Cohen and Klepper (1996) model of cost spreading, which explains the relationship between innovation, firm size and R&D, at the example of the photovoltaic industry in Germany. First, it is analyzed whether the cost spreading mechanism serves as an explanation for size advantages in this industry. This is related to the assumption that the incentives to invest in R&D increase with the ex-ante output. Furthermore, it is investigated whether firms that plan to grow will have more innovative activities. The results indicate that cost spreading serves as an explanation for size advantages in this industry and, furthermore, growth plans lead to higher amount of innovative activities. What is more, the role public policy plays for industry evolution is not finally analyzed in the field of industrial dynamics. In the case of Germany, the introduction of demand inducing policy instruments stimulated market and industry growth. While this policy immediately accelerated market volume, the effect on industry evolution is more ambiguous. Thus, chapter three analyzes this relationship by considering a model of industry evolution, where demand-inducing policies will be discussed as a possible trigger of development. The findings suggest that these instruments can take the same effect as a technical advance to foster the growth of an industry and its shakeout. The fourth chapter explores the regional co-evolution of firm population size, private-sector patenting and public research in the empirical context of German laser research and manufacturing over more than 40 years from the emergence of the industry to the mid-2000s. The qualitative as well as quantitative evidence is suggestive of a co-evolutionary process of mutual interdependence rather than a unidirectional effect of public research on private-sector activities. Chapter five concludes with a summary, the contribution of this work as well as the implications and an outlook of further possible research.

Space System Architecture: Final Report of SSPARC: the Space Systems, Policy, and Architecture Research Consortium (Thrust I and II)

The Space Systems, Policy and Architecture Research Consortium (SSPARC) was formed to make substantial progress on problems of national importance. The goals of SSPARC were to: • Provide technologies and methods that will allow the creation of flexible, upgradable space systems, • Create a “clean sheet” approach to space systems architecture determination and design, including the incorporation of risk, uncertainty, and flexibility issues, and • Consider the impact of national space policy on the above. This report covers the last two goals, and demonstrates that the effort was largely successful.

Japanese Scientific And Technology Information in the United States - Public Policy and Private Initiatives

In January 1983 a group of US government, industry and university information specialists gathered at MIT to take stock of efforts to monitor, acquire, assess, and disseminate Japanese scientific and technical information (JSTI). It was agreed that these efforts were uncoordinated and poorly conceived, and that a clearer understanding of Japanese technical information systems and a clearer sense of its importance to end users was necessary. That meeting led to formal technology assessments, Congressinal hearings, and legislation; it also helped stimulate several private initiatives in JSTI provision. Four years later there exist better coordinated and better conceived JSTI programs in both the public and private sectors, but there remains much room for improvement. This paper will recount their development and assess future directions.

Metacognitive knowledge and self-regulation: A qualitative lecture of students functioning in writing

This research emerges from the world-wide problematic concerning student's failure. It particularly analyzes the meta-cognitive competences in the writing process of this population. Based on Flavell's (1992) viewpoint about meta-cognition and the socio-cognitive approach of self-regulation, two variables were measured: meta-cognitive knowledge and self-regulation strategies. A qualitative study was conducted on a sample of 12 French students at first year university. This study uses a specific technique of interview known as "explicitation interview". The data analysis included the categorization, codification and quantification of the information obtained with the interviews. In conclusion, even though the students had metacognitive knowledge related to the written tasks, they did not show strategies that could help to go beyond the descriptive modality of written discourses by taking into account the readers' expectations. Their writing processes focused on transcription of ideas with little control on the planning and revision phases.

Latino Urbanism, the Politics of Planning, Policy and Redevelopment. Editado por David R. Diaz y Rodolfo D. Torres. Nueva York, New York University Press, 2012

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The Construction of a State Peace Policy and the Process of Conflict Resolution

The academic literature specialized on processes of conflict resolution has focused on how third party intervention and mediation can contribute to end violent conflict, however it has also ignored the potential role of the state in countries affected by internal war. This article calls for a better understanding of the state, not only as a source of contemporary conflict but as a potential advocate of conflict resolution processes. It suggests that it is necessary and possible to involve the state in more effective processes of conflict resolution through the implementation of a State Peace Policy. The central argument is that some of the critical elements that should guide the state action when confronting the destructive logic of war and violence can be effectively undertaken through a public policy focused on building peace. After suggesting a general definition of State Peace Policy and highlighting some of its main attributes, the article recognizes that this sort of policy can also orientate the unfinished process of state consolidation in Colombia and other countries affected by internal conflict. The role of the state in the process of conflict resolution is crucial; however there are some issues normally ignored within the policy-making process, they must be seriously taken into account in order to eliminate the underlying structures that perpetuate conflict and delay the consolidation of sustainable peace.-----La literatura académica especializada en procesos de resolución de conflictos se ha centrado en el estudio de cómo la intervención de terceras partes y la labor de mediación pueden contribuir a poner fin a los conflictos violentos, sin embargo, también ha ignorado el rol potencial del estado en aquellos países afectados por la guerra interna. Este artículo llama la atención sobre la necesidad de estudiar al estado no sólo como la fuente de los conflictos contemporáneos, sino como un colaborador potencial en procesos de resolución de conflictos. Se sugiere que es necesario y también posible involucrar al estado en este tipo de procesos de una manera más efectiva a través de la implementación de una Política de Estado centrada en la Paz. El argumento central es que algunos de los elementos claves que deben guiar la acción del estado cuando éste se enfrenta a la lógica destructiva de la guerra y la violencia, pueden ser efectivamente tratados a través de una política pública que de prioridad a la construcción de la paz. Luego de sugerir una definición general y destacar algunos de los principales atributos de ésta clase de Política de Estado, el artículo reconoce que ésta podría también orientar el proceso inacabado de consolidación del estado en Colombia y en otros países afectados por conflictos internos. El rol del estado en el proceso para resolver los conflictos es crucial, sin embargo hay algunos aspectos normalmente ignorados durante el proceso de formulación de políticas que deben ser tomados en cuenta seriamente para eliminar las estructuras que perpetúan el conflicto y que retrasan la consolidación de la paz sostenible.

Regulation and self-regulation learning. 'Regulación y autoregulación de los aprendizajes'.

Este vídeo nos enseña cómo se produce el proceso de regulación del aprendizaje por el profesor y nos muestra un método alternativo: la propia autoregulación del alumno.