Two component systems: physiological effect of a third component

Signal transduction systems mediate the response and adaptation of organisms to environmental changes. In prokaryotes, this signal transduction is often done through Two Component Systems (TCS). These TCS are phosphotransfer protein cascades, and in their prototypical form they are composed by a kinase that senses the environmental signals (SK) and by a response regulator (RR) that regulates the cellular response. This basic motif can be modified by the addition of a third protein that interacts either with the SK or the RR in a way that could change the dynamic response of the TCS module. In this work we aim at understanding the effect of such an additional protein (which we call ‘‘third component’’) on the functional properties of a prototypical TCS. To do so we build mathematical models of TCS with alternative designs for their interaction with that third component. These mathematical models are analyzed in order to identify the differences in dynamic behavior inherent to each design, with respect to functionally relevant properties such as sensitivity to changes in either the parameter values or the molecular concentrations, temporal responsiveness, possibility of multiple steady states, or stochastic fluctuations in the system. The differences are then correlated to the physiological requirements that impinge on the functioning of the TCS. This analysis sheds light on both, the dynamic behavior of synthetically designed TCS, and the conditions under which natural selection might favor each of the designs. We find that a third component that modulates SK activity increases the parameter space where a bistable response of the TCS module to signals is possible, if SK is monofunctional, but decreases it when the SK is bifunctional. The presence of a third component that modulates RR activity decreases the parameter space where a bistable response of the TCS module to signals is possible.

Targeted inactivation of hypocretin receptors in dopaminergic and noradrenergic systems alters brain activity in wakefulness

Since the discovery of hypocretins/orexins (Hcrt/Ox) in 1998, several narcoleptic mouse models, such as Hcrt-KO, Hcrtrl-KO, Hcrtr2-KO and double receptors KO mice, and orexin-ataxin transgenic mice were generated. The available Hcrt mouse models do not allow the dissection of the specific role of Hcrt in each target region. Dr. Anne Vassalli generated loxP-flanked alleles for each Hcrt receptor, which are manipulated by Cre recombinase to generate mouse lines with disrupted Hcrtrl or Hcrtr2 (or both) in cell type-specific manner. The role of noradrenaline (NA) and dopamine (OA) in ttie regulation of vigilance states is well documented. The purpose of this thesis is to explore the role of the Hcrt input into these two monoaminergic systems. Chronic loss of Hcrtrl in NA neurons consolidated paradoxical sleep (PS), and altered wakefulness brain activity in baseline, during the sleep deprivation (SD), and when mice were challenged by a novel environment, or exposed to nest-building material. The analysis of alterations in the sleep EEG delta power showed a consistent correlation with the changes in the preceding waking quality in these mice. Targeted inactivation of Hcrt input into DA neurons showed that Hcrtr2 inactivation present the strongest phenotype. The loss of Hcrtr2 in DA neurons caused modified brain activities in spontaneous wakefulness, during SD, and in novel environmental conditions. In addition to alteration of wakefulness quality and quantity, conditional inactivation of Hcrtr2 in DA neurons caused an increased in time spent in PS in baseline and a delayed and less complete PS recovery after SD. In the first 30 min of sleep recovery, single (i.e. for Hcrtrl or Hcrtr2) conditional knockout receptor mice had opposite changes in delta activity, including an increased power density in the fast delta range with specific inactivation of Hcrtr2, but a decreased power density in the same range with specific inactivation of Hcrtrl in DA cells. These studies demonstrate a complex impact of Hcrt receptors signaling in both NA and DA system, not only on quantity and quality of wakefulness, but also on PS amount regulation as well as on SWS delta power expression. -- Depuis la découverte des hypocrétines/orexines (Hcrt/Ox) en 1998, plusieurs modèles de souris, narcoleptiques telles que Hcrt-KO, Hcrtr2-KO et récepteurs doubles KO et les souris transgéniques orexine-ataxine ont été générés. Les modèles de souris Hcrt disponibles ne permettaient pas la dissection du rôle spécifique de l'Hcrt dans chaque noyau neuronal cible. Notre laboratoire a généré des allèles loxP pour chacun des 2 gènes codant pour les récepteurs Hcrtr, qui sont manipulés par recombinase Cre pour générer des lignées de souris avec Hcrtrl inactivé, ou Hcrtr2 inactivé, (ou les deux), spécifiquement dans un type cellulaire particulier. Le rôle de la noradrénaline (NA) et la dopamine (DA) dans la régulation des états de vigilance est bien documentée. Le but de cette thèse est d'étudier le rôle de l'afférence Hcrt dans ces deux systèmes monoaminergiques au niveau de l'activité cérébrale telle qu'elle apparaît dans l'électroencéphalogramme (EEG). Mon travail montre que la perte chronique de Hcrtrl dans les neurones NA consolide le sommeil paradoxal (PS), et l'activité cérébrale de l'éveil est modifiée en condition spontanée, au cours d'une experience de privation de sommeil (SD), et lorsque les souris sont présentées à un nouvel environnement, ou exposées à des matériaux de construction du nid. Ces modifications de l'éveil sont corrélées à des modifications de puissance de l'activité delta du sommeil lent qui le suit. L'inactivation ciblée des Hcrtrs dans les neurones DA a montré que l'inactivation Hcrtr2 conduit au phénotype le plus marqué. La perte de Hcrtr2 dans les neurones DA mène à des modification d'activité cérébrale en éveil spontané, pendant SD, ainsi que dans des conditions environnementales nouvelles. En plus de l'altération de la qualité de l'éveil et de la quantité, l'inactivation conditionnelle de Hcrtr2 dans les neurones DA a provoqué une augmentation du temps passé en sommeil paradoxal (PS) en condition de base, et une reprise retardée et moins complète du PS après SD. Dans les 30 premières minutes de la récupération de sommeil, les modèles inactivés pour un seul des récepteurs (ie pour Hcrtrl ou Hcrtr2 seulement) montrent des changements opposés en activité delta, en particulier une densité de puissance accrue dans le delta rapide avec l'inactivation spécifique de Hcrtr2, mais une densité de puissance diminuée dans cette même gamme chez les souris inactivées spécifiquement en Hcrtrl dans les neurones DA. Ces études démontrent un impact complexe de l'inactivation de la neurotransmission au niveau des récepteurs d'Hcrt dans les deux compartiments NA et DA, non seulement sur la quantité et la qualité de l'éveil, mais aussi sur la régulation de quantité de sommeil paradoxal, ainsi que sur l'expression de la puissance delta pendant le sommeil lent.

Landscape Systems and Human Land-Use Interactions in Mediterranean Highlands and Littoral Plains during the Late Holocene: Integrated Analysis from the InterAmbAr Project (North-Eastern Catalonia).

The main goal of the InterAmbAr reseach project is to analyze the relationships between landscape systems and human land-use strategies on mountains and littoral plains from a long-term perspective. The study adopts a high resolution analysis of small-scale study areas located in the Mediterranean region of north-eastern Catalonia. The study areas are distributed along an altitudinal transect from the high mountain (above 2000m a.s.l.) to the littoral plain of Empordà (Fig. 1). High resolution interdisciplinary research has been carried out from 2010, based on the integration of palaeoenvironmental and archaeological data. The micro-scale approach is used to understand human-environmental relationships. It allows better understanding of the local-regional nature of environmental changes and the synergies between catchment-based systems, hydro-sedimentary regimes, human mobility, land-uses, human environments, demography, etc.

Mediterranean-climate streams and rivers: geographically separated but ecologically comparable freshwater systems

Streams and rivers in mediterranean-climate regions (med-rivers in med-regions) are ecologically unique, with flow regimes reflecting precipitation patterns. Although timing of drying and flooding is predictable, seasonal and annual intensity of these events is not. Sequential flooding and drying, coupled with anthropogenic influences make these med-rivers among the most stressed riverine habitat worldwide. Med-rivers are hotspots for biodiversity in all med-regions. Species in med-rivers require different, often opposing adaptive mechanisms to survive drought and flood conditions or recover from them. Thus, metacommunities undergo seasonal differences, reflecting cycles of river fragmentation and connectivity, which also affect ecosystem functioning. River conservation and management is challenging, and trade-offs between environmental and human uses are complex, especially under future climate change scenarios. This overview of a Special Issue on med-rivers synthesizes information presented in 21 articles covering the five med-regions worldwide: Mediterranean Basin, coastal California, central Chile, Cape region of South Africa, and southwest and southern Australia. Research programs to increase basic knowledge in less-developed med-regions should be prioritized to achieve increased abilities to better manage med-rivers.

Assessment of Environmental Impacts of Power Generation

Through indisputable evidence of climate change and its link to the greenhouse gas emissions comes the necessity for change in energy production infrastructure during the coming decades. Through political conventions and restrictions energy industry is pushed toward using bigger share of renewable energy sources as energy supply. In addition to climate change, sustainable energy supply is another major issue for future development plans, but neither of these should come with unbearable price. All the power production types have environmental effects as well as strengths and weaknesses. Although each change comes with a price, right track in minimising the environmental impacts and energy supply security can be found by combining all possible low-carbon technologies and by improving energy efficiency in all sectors, for creating a new power production infrastructure of tolerable energy price and of minor environmental effects. GEMIS-Global Emission Model for Integrated Systems is a life-cycle analysis program which was used in this thesis to make indicative energy models for Finland’s future energy supply. Results indicate that the energy supply must comprise both high capacity nuclear power as well as large variation of renewable energy sources for minimization of all environmental effects and keeping energy price reasonable.

The influence of genetic and environmental factors among MDMA users in cognitive performance

This study is aimed to clarify the association between MDMA cumulative use and cognitive dysfunction, and the potential role of candidate genetic polymorphisms in explaining individual differences in the cognitive effects of MDMA. Gene polymorphisms related to reduced serotonin function, poor competency of executive control and memory consolidation systems, and high enzymatic activity linked to bioactivation of MDMA to neurotoxic metabolites may contribute to explain variations in the cognitive impact of MDMA across regular users of this drug. Sixty ecstasy polydrug users, 110 cannabis users and 93 non-drug users were assessed using cognitive measures of Verbal Memory (California Verbal Learning Test, CVLT), Visual Memory (Rey-Osterrieth Complex Figure Test, ROCFT), Semantic Fluency, and Perceptual Attention (Symbol Digit Modalities Test, SDMT). Participants were also genotyped for polymorphisms within the 5HTT, 5HTR2A, COMT, CYP2D6, BDNF, and GRIN2B genes using polymerase chain reaction and TaqMan polymerase assays. Lifetime cumulative MDMA use was significantly associated with poorer performance on visuospatial memory and perceptual attention. Heavy MDMA users (>100 tablets lifetime use) interacted with candidate gene polymorphisms in explaining individual differences in cognitive performance between MDMA users and controls. MDMA users carrying COMT val/val and SERT s/s had poorer performance than paired controls on visuospatial attention and memory, and MDMA users with CYP2D6 ultra-rapid metabolizers performed worse than controls on semantic fluency. Both MDMA lifetime use and gene-related individual differences influence cognitive dysfunction in ecstasy users.

Ambient intelligence application based on environmental measurements performed with an assistant mobile robot

This paper proposes the use of an autonomous assistant mobile robot in order to monitor the environmental conditions of a large indoor area and develop an ambient intelligence application. The mobile robot uses single high performance embedded sensors in order to collect and geo-reference environmental information such as ambient temperature, air velocity and orientation and gas concentration. The data collected with the assistant mobile robot is analyzed in order to detect unusual measurements or discrepancies and develop focused corrective ambient actions. This paper shows an example of the measurements performed in a research facility which have enabled the detection and location of an uncomfortable temperature profile inside an office of the research facility. The ambient intelligent application has been developed by performing some localized ambient measurements that have been analyzed in order to propose some ambient actuations to correct the uncomfortable temperature profile.

Environmental factors, spatial variation, and specific requirements of Chironomidae in Mediterranean reference streams

Chironomidae spatial distribution was investigated at 63 near-pristine sites in 22 catchments of the Iberian Mediterranean coast. We used partial redundancy analysis to study Chironomidae community responses to a number of environmental factors acting at several spatial scales. The percentage of variation explained by local factors (23.3%) was higher than that explained by geographical (8.5%) or regional factors(8%). Catchment area, longitude, pH, % siliceous rocks in the catchment, and altitude were the best predictors of Chironomidae assemblages. We used a k-means cluster analysis to classified sites into 3 major groups based on Chironomidae assemblages. These groups were explained mainly by longitudinal zonation and geographical position, and were defined as 1) siliceous headwater streams, 2) mid-altitude streams with small catchment areas, and 3) medium-sized calcareous streams. Distinct species assemblages with associated indicator taxa were established for each stream category using IndVal analysis. Species responses to previously identified key environmental variables were determined, and optima and tolerances were established by weighted average regression. Distinct ecological requirements were observed among genera and among species of the same genus. Some genera were restricted to headwater systems (e.g., Diamesa), whereas others (e.g., Eukiefferiella) had wider ecological preferences but with distinct distributions among congenerics. In the present period of climate change, optima and tolerances of species might be a useful tool to predict responses of different species to changes in significant environmental variables, such as temperature and hydrology.

Environmental policy instruments concerning industrial end-use energy efficiency

Energy efficiency and saving energy are the main question marks when thinking of reducing carbon dioxide emissions or cutting costs. The objective of thesis is to evaluate policy instruments concerning end-use energy efficiency of heavy industry in European Union. These policy instruments may be divided in various ways, but in this thesis the division is to administrative, financial, informative and voluntary instruments. Administrative instruments introduced in this thesis are Directive on Integrated Pollution Prevention and Control, Directive on Energy End-use Efficiency and Energy Services, and Climate and Energy Package. Financial means include energy and emission taxation, EU Emission Trading Scheme and diverse support systems. Informative instruments consist of horizontal BAT Reference Document for Energy Efficiency, as well as substantial EU documents including Green Paper on Energy Efficiency, Action Plan for Energy Efficiency and An Energy Policy for Europe. And finally, voluntary instruments include environmental managements systems like ISO 14001 and EMAS, energy auditing and benchmarking. The efficiency of different policy instruments vary quite a lot. Informative instruments lack the commitment from industry and are thus almost ineffective, contrary to EU Emission Trading Scheme, which is said to be the solution to climate problems. The efficiency of administrative means can be placed between those mentioned and voluntary instruments are still quite fresh to be examined fruitfully. However, each instrument has their potential and challenges. Cases from corporate world strengthen the results from theoretical part. Cases were written mainly on the basis of interviews. The interviewees praised the energy efficiency contract of Finnish industry, but the EU ETS takes the leading role of policy instruments. However, for industry the reductions do not come easily.

The Detector Control Systems for the CMS Resistive Plate Chamber at LHC

The RPC Detector Control System (RCS) is the main subject of this PhD work. The project, involving the Lappeenranta University of Technology, the Warsaw University and INFN of Naples, is aimed to integrate the different subsystems for the RPC detector and its trigger chain in order to develop a common framework to control and monitoring the different parts. In this project, I have been strongly involved during the last three years on the hardware and software development, construction and commissioning as main responsible and coordinator. The CMS Resistive Plate Chambers (RPC) system consists of 912 double-gap chambers at its start-up in middle of 2008. A continuous control and monitoring of the detector, the trigger and all the ancillary sub-systems (high voltages, low voltages, environmental, gas, and cooling), is required to achieve the operational stability and reliability of a so large and complex detector and trigger system. Role of the RPC Detector Control System is to monitor the detector conditions and performance, control and monitor all subsystems related to RPC and their electronics and store all the information in a dedicated database, called Condition DB. Therefore the RPC DCS system has to assure the safe and correct operation of the sub-detectors during all CMS life time (more than 10 year), detect abnormal and harmful situations and take protective and automatic actions to minimize consequential damages. The analysis of the requirements and project challenges, the architecture design and its development as well as the calibration and commissioning phases represent themain tasks of the work developed for this PhD thesis. Different technologies, middleware and solutions has been studied and adopted in the design and development of the different components and a big challenging consisted in the integration of these different parts each other and in the general CMS control system and data acquisition framework. Therefore, the RCS installation and commissioning phase as well as its performance and the first results, obtained during the last three years CMS cosmic runs, will be

Eucalyptus ESTs involved in mechanisms against plant pathogens and environmental stresses

Eucalypt plantation has high economical importance in Brazil; however, it has been attacked by various pathogens under different environmental stress conditions. Disease resistance and survival under unfavorable environmental conditions have revealed that the eucalypt has developed highly efficient defense systems. Here we show the results of the Eucalyptus ESTs Genome Project (FORESTs). Using the expressed sequence tags (ESTs) obtained by the Project, contigs of similar sequences from each cDNA library induced and not induced by stress agents were formed, and cDNA sequences similar to other already known molecules, such as plant-signaling molecules, phytoalexins, lignin biosynthesis pathways, PR-proteins and putative genes corresponding to enzymes involved in the detoxification of reactive oxygen species, were identified. We also present general considerations about the mechanisms of Eucalyptus defense against biotic and abiotic stresses. These data are of extreme importance for future eucalypt breeding programs aimed at developing plants with enhanced resistance against pathogens and environmental stresses.

Weather based warning systems for bean angular-leaf-spot and anthracnose

Data available in the literature were used to develop a warning system for bean angular leaf spot and anthracnose, caused by Phaeoisariopsis griseola and Colletotrichum lindemuthianum, respectively. The model is based on favorable environmental conditions for the infectious process such as continuous leaf wetness duration and mean air temperature during this subphase of the pathogen-host relationship cycle. Equations published by DALLA PRIA (1977) showing the interactions of those two factors on the disease severity were used. Excell spreadsheet was used to calculate the leaf wetness period needed to cause different infection probabilities at different temperature ranges. These data were employed to elaborate critical period tables used to program a computerized electronic device that records leaf wetness duration and mean temperature and automatically shows the daily disease severity value (DDSV) for each disease. The model should be validated in field experiments under natural infection for which the daily disease severity sum (DDSS) should be identified as a criterion to indicate the beginning and the interval of fungicide applications to control both diseases.

Effects of thermal environment and supplementation levels on the physiological parameters of moxotó goats in confined and semi-confined rising systems

The objective of this work was to determine the effect of environmental variables and supplementation levels on physiological parameters of Moxotó goats in confined and semi-confined rising systems, in the Brazilian semi-arid region. The semi-confined individuals were kept on a grass based diet during the day and arrested in the end of the afternoon. The confined animals were kept in a management center, receiving two diets composed by forage cactus and maniçoba hay into two different levels (0.5 and 1.5% of the body weight). Inside the management center and in the external environment the environmental comfort parameters were set high during the afternoon period characterizing a situation of thermal discomfort for the animals. During the morning the semi-confined animals presented an average respiratory frequency (69.5 mov min-1) and rectal temperature (39.5 ºC) higher than the confined ones (62.6 mov min-1 and 39.0 ºC, respectively). The confined and semi-confined animals were able to maintain their rectal temperature within normal limits, with increase in the cardiac beatings rate and respiratory frequency. The greater percentage of the used supplementations (1.5%) seemed to increase rectal temperature in the two studied rising systems.

Operational characteristics of four metering systems for agricultural fertilizers and amendments

The use of fertilizers and solid amendments in agriculture generates special interest for their effect on crop productivity, as well as for their environmental impact. The efficient use of these products demands knowing their physical and mechanical properties, the storing conditions effect and the operational characteristics of the metering systems used in the fertilizing equipment. In this context, the present study was developed with the purpose of evaluating the operational characteristics of different fertilizing metering systems and to determine the adequate metering system-product operational parameters, using powder lime, powder gypsum, granular 10-30-10 (N-P-K), and granular urea. Operational differences were established among four types of commercial fertilizer metering systems, including wire auger, star-shaped feed wheel, feed screw and ridged traction wheel. The study found that the unloading rate depends directly on the fertilizer metering system's rotating speed and is affected by particle size, repose angle, bulk density and moisture content of the applied product. The wire auger and star-shaped feed wheel metering systems were adequate for the distribution of powder products and the feed screw for granulated fertilizers. Furthermore, theoretical and experimental characteristic equations were established, defining curves for calibration and handling of the products plus the rotating speed range in which a better distributing behavior was achieved.