c-Jun N-terminal kinase (JNK)-mediated modulation of brain mitochondria function: new target proteins for JNK signalling in mitochondrion-dependent apoptosis

The molecular mechanisms underlying the initiation and control of the release of cytochrome c during mitochondrion-dependent apoptosis are thought to involve the phosphorylation of mitochondrial Bcl-2 and Bcl-x(L). Although the c-Jun N-terminal kinase (JNK) has been proposed to mediate the phosphorylation of Bcl-2/Bcl-x(L) the mechanisms linking the modification of these proteins and the release of cytochrome c remain to be elucidated. This study was aimed at establishing interdependency between JNK signalling and mitochondrial apoptosis. Using an experimental model consisting of isolated, bioenergetically competent rat brain mitochondria, these studies show that (i) JNK catalysed the phosphorylation of Bcl-2 and Bcl-x(L) as well as other mitochondrial proteins, as shown by two-dimensional isoelectric focusing/SDS/PAGE; (ii) JNK-induced cytochrome c release, in a process independent of the permeability transition of the inner mitochondrial membrane (imPT) and insensitive to cyclosporin A; (iii) JNK mediated a partial collapse of the mitochondrial inner-membrane potential (Deltapsim) in an imPT- and cyclosporin A-independent manner; and (iv) JNK was unable to induce imPT/swelling and did not act as a co-inducer, but as an inhibitor of Ca-induced imPT. The results are discussed with regard to the functional link between the Deltapsim and factors influencing the permeability transition of the inner and outer mitochondrial membranes. Taken together, JNK-dependent phosphorylation of mitochondrial proteins including, but not limited to, Bcl-2/Bcl-x(L) may represent a potential of the modulation of mitochondrial function during apoptosis.

A new role for heme, facilitating release of iron from the bacterioferritin iron biomineral

Bacterioferritin (BFR) from Escherichia coli is a member of the ferritin family of iron storage proteins and has the capacity to store very large amounts of iron as an Fe(3+) mineral inside its central cavity. The ability of organisms to tap into their cellular stores in times of iron deprivation requires that iron must be released from ferritin mineral stores. Currently, relatively little is known about the mechanisms by which this occurs, particularly in prokaryotic ferritins. Here we show that the bis-Met-coordinated heme groups of E. coli BFR, which are not found in other members of the ferritin family, play an important role in iron release from the BFR iron biomineral: kinetic iron release experiments revealed that the transfer of electrons into the internal cavity is the rate-limiting step of the release reaction and that the rate and extent of iron release were significantly increased in the presence of heme. Despite previous reports that a high affinity Fe(2+) chelator is required for iron release, we show that a large proportion of BFR core iron is released in the absence of such a chelator and further that chelators are not passive participants in iron release reactions. Finally, we show that the catalytic ferroxidase center, which is central to the mechanism of mineralization, is not involved in iron release; thus, core mineralization and release processes utilize distinct pathways.

The CloudSat mission and the A-train: a new dimension of space-based observations of clouds and precipitation

CloudSat is a satellite experiment designed to measure the vertical structure of clouds from space. The expected launch of CloudSat is planned for 2004, and once launched, CloudSat will orbit in formation as part of a constellation of satellites (the A-Train) that includes NASA's Aqua and Aura satellites, a NASA-CNES lidar satellite (CALIPSO), and a CNES satellite carrying a polarimeter (PARASOL). A unique feature that CloudSat brings to this constellation is the ability to fly a precise orbit enabling the fields of view of the CloudSat radar to be overlapped with the CALIPSO lidar footprint and the other measurements of the constellation. The precision and near simultaneity of this overlap creates a unique multisatellite observing system for studying the atmospheric processes essential to the hydrological cycle.The vertical profiles of cloud properties provided by CloudSat on the global scale fill a critical gap in the investigation of feedback mechanisms linking clouds to climate. Measuring these profiles requires a combination of active and passive instruments, and this will be achieved by combining the radar data of CloudSat with data from other active and passive sensors of the constellation. This paper describes the underpinning science and general overview of the mission, provides some idea of the expected products and anticipated application of these products, and the potential capability of the A-Train for cloud observations. Notably, the CloudSat mission is expected to stimulate new areas of research on clouds. The mission also provides an important opportunity to demonstrate active sensor technology for future scientific and tactical applications. The CloudSat mission is a partnership between NASA's JPL, the Canadian Space Agency, Colorado State University, the U.S. Air Force, and the U.S. Department of Energy.

Communication mechanisms and middleware for distributed video surveillance

A new generation of advanced surveillance systems is being conceived as a collection of multi-sensor components such as video, audio and mobile robots interacting in a cooperating manner to enhance situation awareness capabilities to assist surveillance personnel. The prominent issues that these systems face are: the improvement of existing intelligent video surveillance systems, the inclusion of wireless networks, the use of low power sensors, the design architecture, the communication between different components, the fusion of data emerging from different type of sensors, the location of personnel (providers and consumers) and the scalability of the system. This paper focuses on the aspects pertaining to real-time distributed architecture and scalability. For example, to meet real-time requirements, these systems need to process data streams in concurrent environments, designed by taking into account scheduling and synchronisation. The paper proposes a framework for the design of visual surveillance systems based on components derived from the principles of Real Time Networks/Data Oriented Requirements Implementation Scheme (RTN/DORIS). It also proposes the implementation of these components using the well-known middleware technology Common Object Request Broker Architecture (CORBA). Results using this architecture for video surveillance are presented through an implemented prototype.

Identification of potential mechanisms of toxicity after di-(2-ethylhexyl)-phthalate (DEHP) adult exposure in the liver using a systems biology approach

Phthalates are industrial additives widely used as plasticizers. In addition to deleterious effects on male genital development, population studies have documented correlations between phthalates exposure and impacts on reproductive tract development and on the metabolic syndrome in male adults. In this work we investigated potential mechanisms underlying the impact of DEHP on adult mouse liver in vivo. A parallel analysis of hepatic transcript and metabolic profiles from adult mice exposed to varying DEHP doses was performed. Hepatic genes modulated by DEHP are predominantly PPARalpha targets. However, the induction of prototypic cytochrome P450 genes strongly supports the activation of additional NR pathways, including Constitutive Androstane Receptor (CAR). Integration of transcriptomic and metabonomic profiles revealed a correlation between the impacts of DEHP on genes and metabolites related to heme synthesis and to the Rev-erbalpha pathway that senses endogenous heme level. We further confirmed the combined impact of DEHP on the hepatic expression of Alas1, a critical enzyme in heme synthesis and on the expression of Rev-erbalpha target genes involved in the cellular clock and in energy metabolism. This work shows that DEHP interferes with hepatic CAR and Rev-erbalpha pathways which are both involved in the control of metabolism. The identification of these new hepatic pathways targeted by DEHP could contribute to metabolic and endocrine disruption associated with phthalate exposure. Gene expression profiles performed on microdissected testis territories displayed a differential responsiveness to DEHP. Altogether, this suggests that impacts of DEHP on adult organs, including testis, could be documented and deserve further investigations.

Kinematical analysis of redundant drive wire mechanisms with velocity constraint

In this paper, we propose a new velocity constraint type for Redundant Drive Wire Mechanisms. The purpose of this paper is to demonstrate that the proposed velocity constraint module can fix the orientation of the movable part and to use the kinematical analysis method to obtain the moving direction of the movable part. First, we discuss the necessity of using this velocity constraint type and the possible applications of the proposed mechanism. Second, we derive the basic equations of a wire mechanism with this constraint type. Next, we present a method of motion analysis on active and passive constraint spaces, which is used to find the moving direction of a movable part. Finally, we apply the above analysis method on a wire mechanism with a velocity constraint module and on a wire mechanism with four double actuator modules. By evaluating the results, we prove the validity of the proposed constraint type.

Breaking the impasse: towards a new regime for international climate governance

The reality of the current international order makes it imperative that a just and effective climate regime balance the historical responsibility of developed countries with the increasing absolute emissions from many developing nations. In this short outlook article, key pillars are proposed for a new international climate architecture that envisions replacing the current annex system with two new annexes –Annex α, for countries with high current emissions and historically high emissions, and Annex β, for countries with high current emissions and historically low emissions. Countries in both annexes would implement legally binding targets under this framework. Additionally, this proposal includes tweaks and revisions to funding and technology transfer mechanisms to correct for weaknesses and inequities under the current Kyoto architecture. The proposed framework stems from a belief that a top-down, international approach to climate policy remains the most effective for ensuring environmental integrity. Given the slow rate of institutional learning, reforming and improving the current system is held as a more efficient course of action than abandoning the progress already achieved. It is argued that the proposed framework effectively accommodates key equity, environmental integrity and political feasibility concerns.

Updating existing emotional memories involves the frontopolar/orbitofrontal cortex in ways that acquiring new emotional memories does not

In life, we must often learn new associations to people, places, or things we already know. The current fMRI study investigated the neural mechanisms underlying emotional memory updating. Nineteen participants first viewed negative and neutral pictures and learned associations between those pictures and other neutral stimuli, such as neutral objects and encoding tasks. This initial learning phase was followed by a memory updating phase, during which participants learned picture-location associations for old pictures (i.e., pictures previously associated with other neutral stimuli) and new pictures (i.e., pictures not seen in the first phase). There was greater frontopolar/orbito-frontal (OFC) activity when people learned picture–location associations for old negative pictures than for new negative pictures, but frontopolar OFC activity did not significantly differ during learning locations of old versus new neutral pictures. In addition, frontopolar activity was more negatively correlated with the amygdala when participants learned picture–location associations for old negative pictures than for new negative or old neutral pictures. Past studies revealed that the frontopolar OFC allows for updating the affective values of stimuli in reversal learning or extinction of conditioning [e.g., Izquierdo, A., & Murray, E. A. Opposing effects of amygdala and orbital PFC lesions on the extinction of instrumental responding in macaque monkeys. European Journal of Neuroscience, 22, 2341–2346, 2005]; our findings suggest that it plays a more general role in updating associations to emotional stimuli.

The role of Investment Management Systems in regulatory compliance: a Post-Financial Crisis study of displacement mechanisms

The financial crisis of 2007–2009 and the resultant pressures exerted on policymakers to prevent future crises have precipitated coordinated regulatory responses globally. A key focus of the new wave of regulation is to ensure the removal of practices now deemed problematic with new controls for conducting transactions and maintaining holdings. There is increasing pressure on organizations to retire manual processes and adopt core systems, such as Investment Management Systems (IMS). These systems facilitate trading and ensure transactions are compliant by transcribing regulatory requirements into automated rules and applying them to trades. The motivation of this study is to explore the extent to which such systems may enable the alteration of previously embedded practices. We researched implementations of an IMS at eight global financial organizations and found that overall the IMS encourages responsible trading through surveillance, monitoring and the automation of regulatory rules and that such systems are likely to become further embedded within financial organizations. We found evidence that some older practices persisted. Our study suggests that the institutionalization of technology-induced compliant behaviour is still uncertain.

The end of the opportunism vs trust debate: bounded reliability as a new envelope concept in research on MNE governance

Modern transaction cost economics (TCE) thinking has developed into a key intellectual foundation of international business (IB) research, but the Williamsonian version has faced substantial criticism for adopting the behavioral assumption of opportunism. In this paper we assess both the opportunism concept and existing alternatives such as trust within the context of IB research, especially work on multinational enterprise (MNE) governance. Case analyses of nine global MNEs illustrate an alternative to the opportunism assumption that captures more fully the mechanisms underlying failed commitments inside the MNE. As a substitute for the often-criticized assumption of opportunism, we propose the envelope concept of bounded reliability (BRel), an assumption that represents more accurately and more completely the reasons for failed commitments, without invalidating the other critical assumption in conventional TCE (and internalization theory) thinking, namely the widely accepted envelope concept of bounded rationality (BRat). Bounded reliability as an envelope concept includes two main components, within the context of global MNE management: opportunism as intentional deceit, and benevolent preference reversal. The implications for IB research of adopting the bounded reliability concept are far reaching, as this concept may increase the legitimacy of comparative institutional analysis in the social sciences.

Demand side response: patterns in Europe and future policy perspectives under capacity mechanisms

Demand Side Response (DSR) has been slow to emerge in European electricity markets. This paper aims to both examine the reasons for low levels of DSR in Europe and reflect on factors that might affect the participation of DSR in capacity mechanisms. It relies on available evidence from the literature, secondary data on existing DSR programmes and energy aggregator's data from industries participating in DSR. Findings show that changes to the duration of contracted loads under existing or new programmes might increase the penetration of DSR. The introduction of capacity mechanisms may increase DSR from demand turn down if longer response times were available.

Linguistic relativity in SLA: towards a new research programme

The purpose of the current article is to support the investigation of linguistic relativity in second language acquisition and sketch methodological and theoretical prerequisites toward developing the domain into a full research program. We identify and discuss three theoretical-methodological components that we believe are needed to succeed in this enterprise. First, we highlight the importance of using nonverbal methods to study linguistic relativity effects in second language (L2) speakers. The use of nonverbal tasks is necessary in order to avoid the circularity that arises when inferences about nonverbal behavior are made on the basis of verbal evidence alone. Second, we identify and delineate the likely cognitive mechanisms underpinning cognitive restructuring in L2 speakers by introducing the theoretical framework of associative learning. By doing so, we demonstrate that the extent and nature of cognitive restructuring in L2 speakers is essentially a function of variation in individual learners’ trajectories. Third, we offer an in-depth discussion of the factors (e.g., L2 proficiency and L2 use) that characterize those trajectories, anchoring them to the framework of associative learning, and reinterpreting their relative strength in predicting L2 speaker cognition

New insights into the impact of Lactobacillus population on host-bacteria metabolic interplay

We aimed at evaluating the association between intestinal Lactobacillus sp. composition and their metabolic activity with the host metabolism in adult and elderly individuals. Faecal and plasma metabolites were measured and correlated to the Lactobacillus species distribution in healthy Estonian cohorts of adult (n=16; <48 y) and elderly (n=33; >65 y). Total cholesterol, LDL, C-reactive protein and glycated hemoglobin were statistically higher in elderly, while platelets, white blood cells and urinary creatinine were higher in adults. Aging was associated with the presence of L. paracasei and L. plantarum and the absence of L. salivarius and L. helveticus. High levels of intestinal Lactobacillus sp. were positively associated with increased concentrations of faecal short chain fatty acids, lactate and essential amino acids. In adults, high red blood cell distribution width was positively associated with presence of L. helveticus and absence of L. ruminis. L. helveticus was correlated to lactate and butyrate in faecal waters. This indicates a strong relationship between the composition of the gut Lactobacillus sp. and host metabolism. Our results confirm that aging is associated with modulations of blood biomarkers and intestinal Lactobacillus species composition. We identified specific Lactobacillus contributions to gut metabolic environment and related those to blood biomarkers. Such associations may prove useful to decipher the biological mechanisms underlying host-gut microbial metabolic interactions in an ageing population.