Bases moléculaires et cellulaires d’un trouble neurodéveloppemental causé par l’haploinsuffisance de SYNGAP1.

La déficience intellectuelle est la cause d’handicap la plus fréquente chez l’enfant. De nombreuses évidences convergent vers l’idée selon laquelle des altérations dans les gènes synaptiques puissent expliquer une fraction significative des affections neurodéveloppementales telles que la déficience intellectuelle ou encore l’autisme. Jusqu’à récemment, la majorité des mutations associées à la déficience intellectuelle a été liée au chromosome X ou à la transmission autosomique récessive. D’un autre côté, plusieurs études récentes suggèrent que des mutations de novo dans des gènes à transmission autosomique dominante, requis dans les processus de la plasticité synaptique peuvent être à la source d’une importante fraction des cas de déficience intellectuelle non syndromique. Par des techniques permettant la capture de l’exome et le séquençage de l’ADN génomique, notre laboratoire a précédemment reporté les premières mutations pathogéniques dans le gène à transmission autosomique dominante SYNGAP1. Ces dernières ont été associées à des troubles comportementaux tels que la déficience intellectuelle, l’inattention, des problèmes d’humeur, d’impulsivité et d’agressions physiques. D’autres patients sont diagnostiqués avec des troubles autistiques et/ou des formes particulières d’épilepsie généralisée. Chez la souris, le knock-out constitutif de Syngap1 (souris Syngap1+/-) résulte en des déficits comme l’hyperactivité locomotrice, une réduction du comportement associée à l’anxiété, une augmentation du réflexe de sursaut, une propension à l’isolation, des problèmes dans le conditionnement à la peur, des troubles dans les mémoires de travail, de référence et social. Ainsi, la souris Syngap1+/- représente un modèle approprié pour l’étude des effets délétères causés par l’haploinsuffisance de SYNGAP1 sur le développement de circuits neuronaux. D’autre part, il est de première importance de statuer si les mutations humaines aboutissent à l’haploinsuffisance de la protéine. SYNGAP1 encode pour une protéine à activité GTPase pour Ras. Son haploinsuffisance entraîne l’augmentation des niveaux d’activité de Ras, de phosphorylation de ERK, cause une morphogenèse anormale des épines dendritiques et un excès dans la concentration des récepteurs AMPA à la membrane postsynaptique des neurones excitateurs. Plusieurs études suggèrent que l’augmentation précoce de l’insertion des récepteurs AMPA au sein des synapses glutamatergiques contribue à certains phénotypes observés chez la souris Syngap1+/-. En revanche, les conséquences de l’haploinsuffisance de SYNGAP1 sur les circuits neuronaux GABAergiques restent inconnues. Les enjeux de mon projet de PhD sont: 1) d’identifier l’impact de mutations humaines dans la fonction de SYNGAP1; 2) de déterminer si SYNGAP1 contribue au développement et à la fonction des circuits GABAergiques; 3) de révéler comment l’haploinsuffisance de Syngap1 restreinte aux circuits GABAergiques affecte le comportement et la cognition. Nous avons publié les premières mutations humaines de type faux-sens dans le gène SYNGAP1 (c.1084T>C [p.W362R]; c.1685C>T [p.P562L]) ainsi que deux nouvelles mutations tronquantes (c.2212_2213del [p.S738X]; c.283dupC [p.H95PfsX5]). Ces dernières sont toutes de novo à l’exception de c.283dupC, héritée d’un père mosaïque pour la même mutation. Dans cette étude, nous avons confirmé que les patients pourvus de mutations dans SYNGAP1 présentent, entre autre, des phénotypes associés à des troubles comportementaux relatifs à la déficience intellectuelle. En culture organotypique, la transfection biolistique de l’ADNc de Syngap1 wild-type dans des cellules pyramidales corticales réduit significativement les niveaux de pERK, en fonction de l’activité neuronale. Au contraire les constructions plasmidiques exprimant les mutations W362R, P562L, ou celle précédemment répertoriée R579X, n’engendre aucun effet significatif sur les niveaux de pERK. Ces résultats suggèrent que ces mutations faux-sens et tronquante résultent en la perte de la fonction de SYNGAP1 ayant fort probablement pour conséquences d’affecter la régulation du développement cérébral. Plusieurs études publiées suggèrent que les déficits cognitifs associés à l’haploinsuffisance de SYNGAP1 peuvent émerger d’altérations dans le développement des neurones excitateurs glutamatergiques. Toutefois, si, et auquel cas, de quelle manière ces mutations affectent le développement des interneurones GABAergiques résultant en un déséquilibre entre l’excitation et l’inhibition et aux déficits cognitifs restent sujet de controverses. Par conséquent, nous avons examiné la contribution de Syngap1 dans le développement des circuits GABAergiques. A cette fin, nous avons généré une souris mutante knockout conditionnelle dans laquelle un allèle de Syngap1 est spécifiquement excisé dans les interneurones GABAergiques issus de l’éminence ganglionnaire médiale (souris Tg(Nkx2.1-Cre);Syngap1flox/+). En culture organotypique, nous avons démontré que la réduction de Syngap1 restreinte aux interneurones inhibiteurs résulte en des altérations au niveau de leur arborisation axonale et dans leur densité synaptique. De plus, réalisés sur des coupes de cerveau de souris Tg(Nkx2.1-Cre);Syngap1flox/+, les enregistrements des courants inhibiteurs postsynaptiques miniatures (mIPSC) ou encore de ceux évoqués au moyen de l’optogénétique (oIPSC) dévoilent une réduction significative de la neurotransmission inhibitrice corticale. Enfin, nous avons comparé les performances de souris jeunes adultes Syngap1+/-, Tg(Nkx2.1-Cre);Syngap1flox/+ à celles de leurs congénères contrôles dans une batterie de tests comportementaux. À l’inverse des souris Syngap1+/-, les souris Tg(Nkx2.1-Cre);Syngap1flox/+ ne présentent pas d’hyperactivité locomotrice, ni de comportement associé à l’anxiété. Cependant, elles démontrent des déficits similaires dans la mémoire de travail et de reconnaissance sociale, suggérant que l’haploinsuffisance de Syngap1 restreinte aux interneurones GABAergiques dérivés de l’éminence ganglionnaire médiale récapitule en partie certains des phénotypes cognitifs observés chez la souris Syngap1+/-. Mes travaux de PhD établissent pour la première fois que les mutations humaines dans le gène SYNGAP1 associés à la déficience intellectuelle causent la perte de fonction de la protéine. Mes études dévoilent, également pour la première fois, l’influence significative de ce gène dans la régulation du développement et de la fonction des interneurones. D’admettre l’atteinte des cellules GABAergiques illustre plus réalistement la complexité de la déficience intellectuelle non syndromique causée par l’haploinsuffisance de SYNGAP1. Ainsi, seule une compréhension raffinée de cette condition neurodéveloppementale pourra mener à une approche thérapeutique adéquate.

Prospects of Marketing the Indigenous Ornamental Fishes of Kerala

In this study prospects of marketing the indigenous ornamental fishes of kerala, point out that the export market, consumer preferences in the domestic ornamental fishes, SWOT (strength weakness opportunities and threats) analysis etc. The study notes that the product indigenous ornamental fishes are mostely marketed by exporters and suppliers rather than the retail aquarium shopkeepers. The research findings on the attributes of indigenous ornamental fishes that matches customers preference in aquarium fish.SWOT analysis was carried out to classify the results of the study into strengths,weakness,opportunities and threats faced by the ornamental fish industry in kerala. The marketers in the study show less market perception compaired to the exporters of India. Rather than market survey, interest and experience and raw materials availability inspires them. The developments for large scale marketing have to be carried out, ensuring the sustainable exploitation of the wild fish population by adopting conservation measures such as breeding programmes, quota implementation, setting up of natural sanctuaries to protect the natural resource of ornamental fishes.

STUDIES ON TAXONOMY, DISTRIBUTION, ECOLOGY AND REPRODUCTIVE POTENTIAL OF ROTIFERS FROM SELECTED CENTRES IN COCHIN BACKWATER SYSTEM, KERALA

The studies were conducted in nine stations with varying ecological characteristics along Cochin backwaters and adjoining canals. Many workers opined that the distribution of rotifers is cosmopolitan. The significance of rotifers as first food for early larvae was indicated by Fujita. Aquaculture is a fast growing field in fisheries sector and it is gaining more importance as the fish landings and supply are getting irregular. A consistent supply of fish/shellfish can only be achieved through aquaculture. The success of any culture activity depends on the timely production of seeds of finfishes/shellfishes. The availability of wild seed is seasonal and erratic. So, a dependable source of seed of fishes and shellfishes is possible only through large scale production in hatchery. A successful seed production activity depends on the availability of a variety of suitable live feed organisms in sufficient quantities at the proper time for use in the larval stages. As the live feeds promote high growth rates, easy digestion, assimilation and the quality of not contaminating the culture water when compared to other artificial feeds, make the culture of live feed organisms the principal means of providing food for the larvae of finfishes and shellfishes. Rotifers are considered to be an excellent and indispensable food for larvae of many finfishes and crustaceans. It (1960) was the first to culture Brachionus plicatilis for feeding marine fish larvae, and now it is being extensively used as live feed in hatcheries all over the world. They are a group of microscopic organisms coming under the Phylum Rotifera which comprises of about 2000 species. Their slow swimming habits, ability to tolerate a wide range of salinities, parthenogenetic mode of reproduction and ability to get enriched easily, make rotifers an ideal live feed organism. The major factors such as temperature, salinity and food that influence the reproductive potential and thereby the population size of rotifer, Salinity is one of the most important aspect influencing the reproductive rate of rotifers. The feed type and feed concentration play a vital role in influencing the reproductive rate of rotifers. For culture of rotifers, the commonly used micro algae belong to Chlorella, Nannochloropsis, Isochrysis and Tetraselmis. While some studies have suggested that, algal diet has little effect on reproductive rates in 1979 while using the rotifer, Brachionus plicatilis as feed for the larvae of red sea bream, Pagrus major. It is generally accepted that rotifers play a pivotal role in the successful rearing of marine fish larvae.

Studies on the prevalence of algal blooms along Kerala coast, India

Algal blooms are naturally occurring phenomena in the aquatic environment. These blooms cause mass mortalities of wild and farmed fish and shellfish, human intoxications which sometimes result in death, alteration of marine trophic structure through adverse effects on larvae and other life history stages of commercially important species and death of marine animals. Occurrences of harmful algal blooms and associated mortality have been reported along the coastal waters of India since the early period of the last century. The present study was taken up to study the dynamics of major phytoplankton blooms, which occur along the Kerala coast. The results of quantitative and qualitative analysis of phytoplankton in the coastal waters of Vizhinjam and Chombala, their species diversity and community structure is presented and the major algal blooms recorded along the coast of Kerala during the study period is described and their occurrence is related to the hydrographic and meteorological variations. There is a clear evident from these works in the Indian region that the fishes avoid areas where these harmful algae bloom, either due to the toxicity or due to some irritant property of the chemicals secreted by the algae. Taxonomic diversity studies indicated a change in the community structure of commercial finfishes, crustaceans and molluscs due to the bloom of C.marina and funnel plots indicated the deviation in taxonomic distinctness during the bloom period from theoretical mean for the region.

Multichannel Remote Data Acquisition and Analysing Systems For Fisheries / Environmental Investigations

Remote Data acquisition and analysing systems developed for fisheries and related environmental studies have been reported. It consists of three units. The first one namely multichannel remote data acquisition system is installed at the remote place powered by a rechargeable battery. It acquires and stores the 16 channel environmental data on a battery backed up RAM. The second unit called the Field data analyser is used for insitue display and analysis of the data stored in the backed up RAM. The third unit namely Laboratory data analyser is an IBM compatible PC based unit for detailed analysis and interpretation of the data after bringing the RAM unit to the laboratory. The data collected using the system has been analysed and presented in the form of a graph. The system timer operated at negligibly low current, switches on the power to the entire remote operated system at prefixed time interval of 2 hours.Data storage at remote site on low power battery backedupRAM and retrieval and analysis of data using PC are the special i ty of the system. The remote operated system takes about 7 seconds including the 5 second stabilization time to acquire and store data and is very ideal for remote operation on rechargeable bat tery. The system can store 16 channel data scanned at 2 hour interval for 10 days on 2K backed up RAM with memory expansion facility for 8K RAM.

Communication Parameters in the Marine Fisheries Sector of Kerala-A Study of Kollam Coastal Villages

Department of Applied Economics,Cochin University of Science and Technology

Economics of Ornamental Fisheries in Kerala

Comprehensive studies integrating production, consumption and marketing of ornamental fishes were never conducted in the past in Kerala and this study is an attempt to highlight the dynamics in a systematic manner by making a primary empirical study. The advantages of such an approach are many. First, the study entails detailed empirical data under a given time frame on various inter linked economic activities in ornamental fisheries sector. Second, the study tries to improve upon the previous discipline-bound studies by adopting an integrated approach. As Kerala has diverse ecological and climatic conditions, case studies on various ornamental fish production systems help identifying suitable culture practice for selected environmental conditions. One of the major conclusions of this study as explained in the concluding chapter is that although Kerala is blessed with favourable geographic and climatic conditions needed for developing ornamental fishery, diverse local conditions and requirements contain adopting modern methods of enterprise development.Consumer studies conducted would help to identify the demand of ornamental fishes and the factors leading to it. Market studies would help in understanding the forces behind domestic market, which is very promising, but neglected. Viability studies throw light on the economic performance of both the production systems and the trading units of ornamental fishes. Despite the economic significance of ornamental fisheries industry, its development has been constrained due to various bio-technical, cultural, socio-economic, organisational and above all, institutional and policy failures. The outcome of the study would identify constraints facing the industry and institutional arrangements for development.

Institutional Dynamics in Community-Based Fisheries Resources Management for Sustainable Development of Marine Fisheries in Kerala

Department of Applied Economics, Cochin University of Science and Technology

Systematics and biology of Fishes of family of the hemiramphidae of Cochin coast

This overall focus of the thesis involves the systematics and biology of fishes of the family hemiramphidae of cochin coast.India is one of the leading fish producing nations in the world with an average annual production of 6.1 million tonnes of fish and shell fish from capture and culture fisheries in 2001 (Ayyappan and Biradar, 2002).Fisheries play a very significant role in the Indian economy by providing employment to nearly 7 million people directly or indirectly, supplying rich protein food and earning valued foreign exchange.Fishes of the family Hemiramphidae are commonly called ‘half beaks‘.In India, studies on hemiramphids commenced with the work of Day (1878,1889) who recorded thirteen species of hemiramphids from the Indian waters.The study area, which is part of Cochin coast is located between Lat.9°28’ and 10° N and Long.76° 13’ and 76° 31 E. Lying parallel to it is an estuary which is commonly called the Cochin backwaters which has a total area of about 200 sq.miles.The study area is subjected to wide variations in salinity from place to place, season and surface to bottom.The Cochin coast and the adjacent back water system of Kerala has a rich and diversified fish fauna. The hemiramphid fishes constitute a minor fishery of this area.The study on the distribution and availability of hemiramphid fishes present in the Cochin coast shows that they evince different patterns of distribution.In the present study it is noticed that fecundity has high correlation with weight than length of the fish.Histological studies revealed that the spermatogenesis in both H. (H) limbatus and H.(H) xanthopterus, consists of spermatogonia, primary spermatocytes secondary, spermatocytes, spermatids and spermatozoa whereas in the oogenesis of both the species.biological study will be useful in implementation of proper measures of conservation and management so that further devastation of the hemiramphids of Cochin Coast can be controlled.

Resource abundance and Survival of indigenous ornamental fishes of central Kerala with emphasis on handling and packing stress in Puntius filamentosus(VALENCIENNES)

This thesis Entitled Resource abundance and survival of indigenous ornamental fishes of central kerala with emphasis on handling and packing stress in puntius filamentosus (valenciennes).Kerala state is endowed with 41 west flowing and three east flowing rivers originating in the Western Ghats. These rivers and their vast network of tributaries and distributaries harbour rich and diversified fish fauna. Most of the freshwater fishes available in Kerala are highly appreciated as ornamental fishes in the national and international markets.Today the ornamental fish industry is one of the largest industries all over the world. The demand for ornamental fishes has been increasing steadily with the enlargement of the industry, such that the current demand for indigenous ornamental fishes have exceeded the supply. This has led to serious concern about the resources available in the country that can be utilised judiciously for the economic benefit of the state. With an aim to fill up the lacuna, a database of freshwater ornamental fishes of Kerala was created as part of the present study. Ornamental fishes destined for export marketing should thrive well in the aquarium conditions.The study reiterates fishes caught from different environmental conditions and feeding habits have a greater ability to adapt and acclimatise to an entirely new environment and food habits. Marketing studies based on the statistics available with Marine Products Export Development Authority show that these species are not being exported at the required level over the past 6 years, when compared to the availability in the water bodies of Kerala. Sustainable utilisation of these resources from the wild using modern management principles and code of conduct for responsible fishing are advisable until captive breeding technology is popularised.

Pathological Investigations in penaeid Prawns

The thesis embodies the results of the studies carried out on certain diseases affecting the commercially important penaeid prawns in the capture and culture fisheries of the southwest and southeast coasts of india during october, 1981 to april 1985.initially a survey is conducted to obtain information and to understand the commom diseases and abnormalities occurring in the penaeid prawms in nature and those farmed. A result of the survey then cases of diseases and abnormalities are reported. These include tumour like growth soft prawm syndrome, tail necrosis brown spot disease, red rostrum, ciliate infestation ,helminth parasitisation,metacercarial infestation and bopyrid infestation in the penaeid prawns such as penaeus indicus p. monodon , p. semisulcatus ,Metapenaeus dobsoni and m.affinis.The symptoms ,occurrence and incidence of each of the above cases are provided along with the information on environmental factors such as salinity,dissolved oxygen,temperature and ph of the water from the collection sites. The nature of the disease,the tissuse of the host that are affected by the infection or infestation or by the pathogen ,and the actors influencing the infection in each of the ten cases are studied histopathologically and discussed. In the light of the available published information, the control measures for the different diseases of penaeid prawns are presented and discussed.

The Impact of Integrated Marine Fisheries ‘Development Project Among the Artisanal Fishermen in Kerala

Despite various intervensions, artisanal fishermen remain one of the weaker sections in Kerala's society. Host of the welfare and developmental programmes introduced for them had produced very little impact on their living conditions. Further, they are unable to compete with mechanised sector for fishing. Host of the technological development which had taken place after Indo-Norvegean Project favoured the growth of mechanised sector. As a consequence of this, fishing become unviable for artisanal fishermen who propagate the idea of ” sustainable development” in the fishing industry. It is commonly believed that an integrated approach may help them to improve their living conditions substantially. In the light of the above background the scholar has made an attempt to study the impact of Integrated Marine Fisheries Development Project among artisanal fishermen in Kerala It is realised from the findings of the study that the most important needs of artisanal fishermen arecredit facilities and marketing support. Without marketing linkages effective credit management is not possible. Marketing activities and credit management are interdependent

Role of Commission Agents in the Development of Traditional Marine Fisheries of Kerala with Special Reference to Financing

The study clearly brings out the role of commission agents in the traditional marine fisheries sector and thereby goes to set at rest the controversy regarding their role. The findings of the study has important implications for formulation of policies and development strategies related to the traditional marine fisheries sector. The study points out the need for a thorough review and reformulation of the policies and development strategies for efficiently achieving the development potential of the traditional marine fisheries sector and for improving the economic conditions of the fishermen. The study is based mostly on Alappuzha District of Kerala, covering all the 30 marine fishing villages, spread over the three coastal taluks, namely, Karthikappally, Ambalappuzha and Cherthala

Studies On Some Aspects Of Biology Of Two Estuarine Fishes Megalops Cyprinoides And Scatophagus Argus

Based on the adaption of fishes to their habitat, they are divided into three ecological groups - marine, fresh water and estuarine or brackish water forms. Estuarine fishes inhabit the less saline region of the sea, estuaries and other inland waters. These fishes are more subjected to pollution than fresh water fishes or marine fishes as they encounter pollutants present in the outgoing river water and the incoming sea water during low and high tides respectively. So, the study of the biology of the estuarine fishes has become unavoidable to assess their suitability in aquaculture. The development of both capture and culture fisheries related to any brackish water system is dependent on the availability of scientific‘ data on the various biological factors in respect of the different species. Such a study on fishes will be helpful in formulating suitable schemes for the management of brackish water for capture and culture fisheries. It was therefore felt that a study of the biological and biochemical aspects of two estuarine fishes Megalops cyprinoides Broussonet and Scatophargus Bloch which are not fully exploited in aquaculture programmes, was worth undertaking. The present study is expected to advance our knowledge on the biology of the two fishes which are very desirable for brackish water fish farming