A proteome-wide strategy reveals a novel mechanism of control of cell cycle progression through modulation of cyclin mRNA stability

La quantité de données générée dans le cadre d'étude à grande échelle du réseau d'interaction protéine-protéine dépasse notre capacité à les analyser et à comprendre leur sens; d'une part, par leur complexité et leur volume, et d'un autre part, par la qualité du jeu de donnée produit qui semble bondé de faux positifs et de faux négatifs. Cette dissertation décrit une nouvelle méthode de criblage des interactions physique entre protéines à haut débit chez Saccharomyces cerevisiae, la complémentation de fragments protéiques (PCA). Cette approche est accomplie dans des cellules intactes dans les conditions natives des protéines; sous leur promoteur endogène et dans le respect des contextes de modifications post-traductionnelles et de localisations subcellulaires. Une application biologique de cette méthode a permis de démontrer la capacité de ce système rapporteur à répondre aux questions d'adaptation cellulaire à des stress, comme la famine en nutriments et un traitement à une drogue. Dans le premier chapitre de cette dissertation, nous avons présenté un criblage des paires d'interactions entre les protéines résultant des quelques 6000 cadres de lecture de Saccharomyces cerevisiae. Nous avons identifié 2770 interactions entre 1124 protéines. Nous avons estimé la qualité de notre criblage en le comparant à d'autres banques d'interaction. Nous avons réalisé que la majorité de nos interactions sont nouvelles, alors que le chevauchement avec les données des autres méthodes est large. Nous avons pris cette opportunité pour caractériser les facteurs déterminants dans la détection d'une interaction par PCA. Nous avons remarqué que notre approche est sous une contrainte stérique provenant de la nécessité des fragments rapporteurs à pouvoir se rejoindre dans l'espace cellulaire afin de récupérer l'activité observable de la sonde d'interaction. L'intégration de nos résultats aux connaissances des dynamiques de régulations génétiques et des modifications protéiques nous dirigera vers une meilleure compréhension des processus cellulaires complexes orchestrés aux niveaux moléculaires et structuraux dans les cellules vivantes. Nous avons appliqué notre méthode aux réarrangements dynamiques opérant durant l'adaptation de la cellule à des stress, comme la famine en nutriments et le traitement à une drogue. Cette investigation fait le détail de notre second chapitre. Nous avons déterminé de cette manière que l'équilibre entre les formes phosphorylées et déphosphorylées de l'arginine méthyltransférase de Saccharomyces cerevisiae, Hmt1, régulait du même coup sont assemblage en hexamère et son activité enzymatique. L'activité d'Hmt1 a directement un impact dans la progression du cycle cellulaire durant un stress, stabilisant les transcrits de CLB2 et permettant la synthèse de Cln3p. Nous avons utilisé notre criblage afin de déterminer les régulateurs de la phosphorylation d'Hmt1 dans un contexte de traitement à la rapamycin, un inhibiteur de la kinase cible de la rapamycin (TOR). Nous avons identifié la sous-unité catalytique de la phosphatase PP2a, Pph22, activé par l'inhibition de la kinase TOR et la kinase Dbf2, activé durant l'entrée en mitose de la cellule, comme la phosphatase et la kinase responsable de la modification d'Hmt1 et de ses fonctions de régulations dans le cycle cellulaire. Cette approche peut être généralisée afin d'identifier et de lier mécanistiquement les gènes, incluant ceux n'ayant aucune fonction connue, à tout processus cellulaire, comme les mécanismes régulant l'ARNm.

Understanding the transcriptional control of EIF4E and its dysregulation in acute myeloid leukemia: role of NF-κB

EIF4E, le facteur d’initiation de la traduction chez les eucaryotes est un oncogène puissant et qui se trouve induit dans plusieurs types de cancers, parmi lesquels les sous-types M4 et M5 de la leucémie aiguë myéloblastique (LAM). EIF4E est régulé à plusieurs niveaux cependant, la régulation transcriptionnelle de ce gène est peu connue. Mes résultats montrent que EIF4E est une cible transcriptionnelle directe du facteur nucléaire « kappa-light- chain- enhancer of activated B cells » (NF-κB).Dans les cellules hématopoïétiques primaires et les lignées cellulaires, les niveaux de EIF4E sont induits par des inducteurs de NF-κB. En effet, l’inactivation pharmaceutique ou génétique de NF-κB réprime l’activation de EIF4E. En effet, suite à l’activation de NF-κB chez l’humain, le promoteur endogène de EIF4E recrute p65 (RelA) et c-Rel aux sites évolutionnaires conservés κB in vitro et in vivo en même temps que p300 ainsi que la forme phosphorylée de Pol II. De plus, p65 est sélectivement associé au promoteur de EIF4E dans les sous-types LAM M4/M5 mais non pas dans les autres sous-types LAM ou dans les cellules hématopoïétiques primaires normales. Ceci indique que ce processus représente un facteur essentiel qui détermine l’expression différentielle de EIF4E dans la LAM. Les analyses de données d’expressions par séquençage de l’ARN provenant du « Cancer Genome Atlas » (TCGA) suggèrent que les niveaux d’ARNm de EIF4E et RELA se trouvent augmentés dans les cas LAM à pronostic intermédiaire ou faible mais non pas dans les groupes cytogénétiquement favorables. De plus, des niveaux élevés d’ARNm de EIF4E et RELA sont significativement associés avec un taux de survie relativement bas chez les patients. En effet, les sites uniques κB se trouvant dans le promoteur de EIF4E recrutent le régulateur de transcription NF-κB p65 dans 47 nouvelles cibles prévues. Finalement, 6 nouveaux facteurs de transcription potentiellement impliqués dans la régulation du gène EIF4E ont été prédits par des analyses de données ChIP-Seq provenant de l’encyclopédie des éléments d’ADN (ENCODE). Collectivement, ces résultats fournissent de nouveaux aperçus sur le control transcriptionnel de EIF4E et offrent une nouvelle base moléculaire pour sa dérégulation dans au moins un sous-groupe de spécimens de LAM. L’étude et la compréhension de ce niveau de régulation dans le contexte de spécimens de patients s’avère important pour le développement de nouvelles stratégies thérapeutiques ciblant l’expression du gène EIF4E moyennant des inhibiteurs de NF-κB en combinaison avec la ribavirine.

Studies on the Development and Control of Desiccation cracks in compacted clay liner soils

The present study aimed at critically looking at the current practice of the installation of compacted clay liner using bentonite enhanced sand (BES). The application of bentonite is currently the most accepted practice for lining purposes. The ideal bentonite sand combination, which satisfies the liner requirements is 20% bentonite and 80% sand, was selected as one of the liner materials for the investigation of development of desiccation cracks. Locally available sundried marine clay and its combination with bentonite were also included in the study. The desiccation tests on liner materials were conducted for wet/dry cycles to simulate the seasonal variations. Digital image processing techniques were used to measure the crack intensity factor (CIF), a useful and effective parameter for quantification of desiccation cracking. The repeatability of the tests could be well established, as the variation in CIF values of identical samples had a very narrow range of 0 to 2%. The studies on the development of desiccation cracks showed that the CIF of bentonite enhanced sand mixture (BES) was 18.09%, 39.75% and 21.22% for the first, second and third cycles respectively, while it was only 9.83%, 7.52% and 4.58% respectively for sun dried marine clay (SMC). Thus the locally available, alternate liner material suggested, viz SMC, is far superior to BES, when subjected to alternate wet/dry cycles. Further, the improvement of these liner materials when amended with randomly distributed fibre reinforcements was also investigated. Three types of fibres ,namely nylon fibre, polypropylene monofilament and polypropylene fibre mesh were used for the study of fibre amended BES and SMC.The influence of these amendments on the properties of the above liner materials is also studied. The results showed that there is definite improvement in the properties of the liner materials when it is reinforced with discrete random fibres. The study also proved that the desiccation cracks could be controlled with the help of fibre reinforcement.

Synchronization and control of chaos in coupled chaotic multimode Nd:YAG lasers

In this Letter we numerically investigate the dynamics of a system of two coupled chaotic multimode Nd:YAG lasers with two mode and three mode outputs. Unidirectional and bidirectional coupling schemes are adopted; intensity time series plots, phase space plots and synchronization plots are used for studying the dynamics. Quality of synchronization is measured using correlation index plots. It is found that for laser with two mode output bidirectional direct coupling scheme is found to be effective in achieving complete synchronization, control of chaos and amplification in output intensity. For laser with three mode output, bidirectional difference coupling scheme gives much better chaotic synchronization as compared to unidirectional difference coupling but at the cost of higher coupling strength. We also conclude that the coupling scheme and system properties play an important role in determining the type of synchronization exhibited by the system.

Control of bistability in a directly modulated semiconductor laser using delayed optoelectronic feedback

We show numerically that direct delayed optoelectronic feedback can suppress hysteresis and bistability in a directly modulated semiconductor laser. The simulation of a laser with feedback is performed for a considerable range of feedback strengths and delays and the corresponding values for the areas of the hysteresis loops are calculated. It is shown that the hysteresis loop completely vanishes for certain combinations of these parameters. The regimes for the disappearance of bistability are classified globally. Different dynamical states of the laser are characterized using bifurcation diagrams and time series plots.

Legal Control of Fishing Industry in Kerala

This work is a study on ‘Legal Control of Fishing Industry in Kerala.Fishery and Fishery-related legislations are sought to be examined in the light of scientific opinion and judicial decisionsThis work is divided into five Part.The thrust of time Study is on the success of legislative measures in attempting to achieve socio-economic justice for the fishermen community.Fishing is more an avocation than an industry. It is basically the avocation of the artisanal or traditional fishermen who depend on it for their livelihood. As an ‘industry’, it is a generator of employment, income and wealth.The modern tendency in national legislations is to integrate legal proivisions relating to EEZ fisheries into the general fisheries legislation.Chartered fishing was introduced by the Central Government during 1977-78 to establish the abundance and distribution of fishery resources in Indian EEZ, for transfer of technology and for related purposes.Going by the provisions of Articles 61 and 62 of the U.N. Convention on the Law of the Sea, 1982, foreign fishing need be permitted in our EEZ area only if there is any surplus left after meeting our national requirements.Conservation of the renewable fishery resources should start with identification of the species, their habitats, feeding and breeding patterns, their classification and characteristics. Fishing patterns and their impact on different species and areas require to be examined and investigated.the Central Government, that the Kerala Marine Fishing Regulation Act, 1980 was passed.our traditional fishermen that our Governments in power in Kerala resorted to the appointment of Commissions after Commissions to enquire into the problems of resource management and conservation of the resources. The implementation of the recommendations of these Commissions is the need of the times.General infrastructure has increased to a certain extent in the fishery villages; but it is more the result of the development efforts of the State rather than due to increase in earnings from fishing. Fisherwomen ar e still unable to enjoy the status and role expected of them in the society and the family.Around 120 million people around the tuorld are economically dependent on fisheries. In developing countries like India, small-scale fishers are also the primary suppliers of fish, particularly for local consumption. A most important role of the fisheries sector is as a source of domestically produced food. Fish, as a food item, is a nutrient and it has great medicinal value.Consumers in our country face a dramatic rise in fish prices as our ‘fishing industry’ is linked with lucrative markets in industrial countries. Autonomy of States should be attempted to be maintained to the extent possible with the help and co-operation of the Centre. Regional co-operation of the coastal states interse and with the Centre should be attempted to be achieved under the leadership of the Centre in matters of regional concern. At time national level, a ifisheries management policy and plan should be framed in conformity with the national economic policies and plans as also keeping pace with the local and regional needs and priorities. Any such policy, plan and legislation should strive to achieve sustainability of the resources as well as support to the subsistence sector.

Legal Control of Industrial Pollution

Industries constitute the main spring of development. Without industrial development no country could reach a stage in which a decent living for its citizens would be achieved. Increasing production to meet the basic needs of society augmented scientific invention and machine oriented industrial order.Environmental pollution ls a burning global issue. It is more serious and dangerous than terrorism. Started with the discovery of fire and development of civilization. Pollution went unnoticed throughout the centuries of human growth until its adverse effects on human environment become explicit.National concern tor environment started in our country only atter the cause of protection of environment received global attention. At present legal control ot industrial pollution is in a scattered framework of piece meal processes with overlapping provisions and authorities.Environmental protection- should be an item not only in the concurrent list of schedule 7 to the Constitution but also in the list of matters entrusted to the panchayati institutions in the Schedule 11. It is heartening to note that so far as municipalities are concerned the Constitution of India lives up to the expectation. In the wake of New Industrial Policy based on liberalisation a long list of small scale industries fall outside the purview of environmental clearance. The Indian concept of environmental im»act assessment introduced under the Environment Act by notification excludes the entire gamut of small scale industries and r.elates only to scheduled industries covered by the notifica~ion. Most of them are subjected to ETA only it the investment goes above ~.50 crores. This provision dilutes the impact assessment considerably A mandatory impact assessment with public partiCipation and with provision for a review by specialized environmental courts will eliminate the possible evils of this judicial passiveness.

A study on community participation in disease control programmes, with references to control of filariasis in Alappuzha District

This thesis throws light on the influence of community in the social life of mankind. The study revolves round the fact that health care is by the people rather than health care is for the people. The thesis tries to analyze the role of community organizational social agencies in the control of Filariasis.The study examines the factors which influence community participation. and the effectiveness of health education in the control of Filariasis.the thesis emphasizes the effective tools and means of health education That helps to To evolve an appropriate method for the management of community Participation. The study shows that. A well informed community can participate successfully and meaningfully in disease control programmes.

Administrative control of companies in India

The joint stock company is an institution wielding immense socio economic _power over the ultimate progress and well -being of the nation. It is subjected to corresponding definable responsibilities towards all who depend on than. the shareholders.the employees the suppliers of raw materials. the consumers of its product: and society at Large. The company law is changing and must change with time and take note of the dynamics of trade and industry. Obviously it cannot be static and permanent while the basic economic and social philosophies and the technique of production and investment in the industrial sector change.‘ It provides a legal framework for the corporate form of business in which the organization capital and labour are brought. together in a particular form of relationship. The activities carried on within this corporate form is subjected to a gradual but steadily increasing control by the Government. A study of this oontrol is undertaken to better understand the present law and to suggest the path for further change

Socio economic factors influencing the persistence and control of filariasis in Kerala-A case study of malayan filariasis in Cherthala

In general the behavioural sciences have contributed very little to filariasis research.Man's actions in creating vector breeding sites have been noted and discussed frequently inthe frlariasis literature. but virtually no systematic studies of these fonns of behavior have been undertaken (Dunn. 1979). Human behavioural observations and inquires into values and attitudes atfecting behavior that inhibits or promotes vector breeding are essential if any progress is to be made in developing self help programmes of vector control. Therefore, a systematic study on the socio-economic aspect of the community is warranted before undertaking any control programme against filariasis. In view of this the present study has been carried out which reveals the knowledge, attitude and practice concerning the causation, transmission, treatment and control of the disease. Socio economic factors that influence the creation and maintenance of vector breeding habitats were identified. characterization and ranking of these sociological factors will be helpful in identifying the determinants of human behavioural changes towards the containment of the disease- Information on the existing indigenous perception of the disease and the factors that hinder the control will be useful in developing a sound strategy from the human angle, which can be put to practical use.

Study of Synchronisalion and Control of Chaos in Directly Modulated Semiconductor Lasers

Chaos is a subject oftopical interest and, studied in great detail in relation to its relevance in almost all branches of science, which include physical, chemical, and biological fields. Chaos in the literal sense signifies utter confusion, but the scientific community has differentiated chaos as deterministic chaos and white noise. Deterministic chaos implies the complex behaviour of systems, which are governed by deterministic laws. Behaviour of such systems often become unpredictable in the long run. This unpredictability arises from the sensitivity of the system to its initial conditions. The essential requirement for ‘sensitivity to initial condition’ is nonlinearity of the system. The only method for determining the future of such systems is numerically simulating its final state from a set ofinitial conditions. Synchronisation

Anti-lipopolysaccharide factor and crustin-III, the anti-white spot virus peptides in Penaeus monodon: Control of viral infection by up-regulation

White Spot Syndrome Virus (WSSV) is the most devastating disease affecting shrimp culture around the world. Though, considerable progress has been made in the detection and molecular characterization of WSSV in recent years, information pertaining to immune gene expression in shrimps with respect to WSSV infection remains limited. In this context, the present study was undertaken to understand the differential expression of antimicrobial peptide (AMP) genes in the haemocytes of Penaeus monodon in response to WSSV infection on a time-course basis employing semi-quantitative RT-PCR. The present work analyzes the expression profile of six AMP genes (ALF, crustin-1, crustin-2, crustin-3, penaeidin-3 and penaeidin-5), eight WSSV genes (DNA polymerase, endonuclease, immediate early gene, latency related gene, protein kinase, ribonucleotide reductase, thymidine kinase and VP28) and three control genes (18S rRNA, β-actin and ELF) in P. monodon in response to WSSV challenge. Penaeidins were found to be up-regulated during early hours of infection and crustin-3 during late period of infection. However, ALF was found to be up-regulated early to late period of WSSV infection. The present study suggests that AMPs viz. ALF and crustin-3 play an important role in antiviral defense in shrimps. WSSV gene transcripts were detected post-challenge day 1 itself and increased considerably day 5 onwards. Evaluation of the control genes confirmed ELF as the most reliable control gene followed by 18S rRNA and β-actin for gene expression studies in shrimps. This study indicated the role of AMPs in the protection of shrimps against viral infection and their possible control through the up-regulation of AMPs

Indian Law on Control of Vessel Sourced Pollution in Maritime Ports

Maritime ports are inevitable for India’s economic development. The very existence and sustainable development of ports depend on clean port environment. There is a notion that shipping is an over regulated industry. But in India, it is being operated under sub- standard conditions, raising crucial issues of environmental pollution in the country’s ports. The negative impacts of vessel sourced pollution on the eco-fragile coastal peninsula can be detrimental to the living conditions, health and interests of the coastal population. It can disturb marine life and imbalance the aquatic ecosystem. The present study analyses control of vessel sourced pollution in Indian ports from an economic and ecological perspective. The study investigates legal reasons behind the weak control, regulation and monitoring over vessel sourced pollution in Indian ports. The loopholes in the legal system are identified and suggestion made to implement stronger enforcement. Unless, vessel operations are properly regulated in ports, the trade and economic prospects of India will be jeopardized.

Methods for short-term control of Imperata grass in Peruvian Amazon

The traditional control of Imperata brasiliensis grasslands used by farmers in the Peruvian Amazon is to burn the grass. The objective of this study was to compare different methods of short-term control. Biological, mechanical, chemical and traditional methods of control were compared. Herbicide spraying and manual weeding have shown to be very effective in reducing above- and below-ground biomass growth in the first 45 days after slashing the grass, with effects persisting in the longer term, but both are expensive methods. Shading seems to be less effective in the short-term, whereas it influences the Imperata growth in the longer term. After one year shading, glyphosate application and weeding significantly reduced aboveground biomass by 94, 67 and 53%; and belowground biomass by 76, 65 and 58%, respectively, compared to control. We also found a significant decrease of Imperata rhizomes in soil during time under shading. Burning has proved to have no significant effect on Imperata growth. The use of shade trees in a kind of agroforestry system could be a suitable method for small farmers to control Imperata grasslands.