Solution structure of DFF40 and DFF45 N-terminal domain complex and mutual chaperone activity of DFF40 and DFF45

Apoptotic DNA fragmentation is mediated by a caspase-activated DNA fragmentation factor (DFF)40. Expression and folding of DFF40 require the presence of DFF45, which also acts as a nuclease inhibitor before DFF40 activation by execution caspases. The N-terminal domains (NTDs) of both proteins are homologous, and their interaction plays a key role in the proper functioning of this two-component system. Here we report that the NTD of DFF45 alone is unstructured in solution, and its folding is induced upon binding to DFF40 NTD. Therefore, folding of both proteins regulates the formation of the DFF40/DFF45 complex. The solution structure of the heterodimeric complex between NTDs of DFF40 and DFF45 reported here shows that the mutual chaperoning includes the formation of an extensive network of intermolecular interactions that bury a hydrophobic cluster inside the interface, surrounded by intermolecular salt bridges.

Ribonucleoprotein infrastructure regulating the flow of genetic information between the genome and the proteome

Following transcription and splicing, each mRNA of a mammalian cell passes into the cytoplasm where its fate is in the hands of a complex network of ribonucleoproteins (mRNPs). The success or failure of a gene to be expressed depends on the performance of this mRNP infrastructure. The entry, gating, processing, and transit of each mRNA through an mRNP network helps determine the composition of a cell's proteome. The machinery that regulates storage, turnover, and translational activation of mRNAs is not well understood, in part, because of the heterogeneous nature of mRNPs. Recently, subsets of cellular mRNAs clustered as members of mRNP complexes have been identified by using antibodies reactive with RNA-binding proteins, including ELAV/Hu, eIF-4E, and poly(A)-binding proteins. Cytoplasmic ELAV/Hu proteins are involved in the stability and translation of early response gene (ERG) transcripts and are expressed predominately in neurons. mRNAs recovered from ELAV/Hu mRNP complexes were found to have similar sequence elements, suggesting a common structural linkage among them. This approach opens the possibility of identifying transcripts physically clustered in vivo that may have similar fates or functions. Moreover, the proteins encoded by physically organized mRNAs may participate in the same biological process or structural outcome, not unlike operons and their polycistronic mRNAs do in prokaryotic organisms. Our goal is to understand the organization and flow of genetic information on an integrative systems level by analyzing the collective properties of proteins and mRNAs associated with mRNPs in vivo.

Regulation of Actin Tension in Plant Cells by Kinases and Phosphatases1

Changes in the organization and mechanical properties of the actin network within plant and animal cells are primary responses to cell signaling. These changes are suggested to be mediated through the regulation of G/F-actin equilibria, alterations in the amount and/or type of actin-binding proteins, the binding of myosin to F-actin, and the formation of myosin filaments associated with F-actin. In the present communication, the cell optical displacement assay was used to investigate the role of phosphatases and kinases in modifying the tension and organization within the actin network of soybean cells. The results from these biophysical measurements suggest that: (a) calcium-regulated kinases and phosphatases are involved in the regulation of tension, (b) calcium transients induce changes in the tension and organization of the actin network through the stimulation of proteins containing calmodulin-like domains or calcium/calmodulin-dependent regulatory proteins, (c) myosin and/or actin cross-linking proteins may be the principal regulator(s) of tension within the actin network, and (d) these actin cross-linking proteins may be the principal targets of calcium-regulated kinases and phosphatases.

The Three-Dimensional Structure of Aspergillus niger Pectin Lyase B at 1.7-Å Resolution1

The three-dimensional structure of Aspergillus niger pectin lyase B (PLB) has been determined by crystallographic techniques at a resolution of 1.7 Å. The model, with all 359 amino acids and 339 water molecules, refines to a final crystallographic R factor of 16.5%. The polypeptide backbone folds into a large right-handed cylinder, termed a parallel β helix. Loops of various sizes and conformations protrude from the central helix and probably confer function. The largest loop of 53 residues folds into a small domain consisting of three antiparallel β strands, one turn of an α helix, and one turn of a 310 helix. By comparison with the structure of Erwinia chrysanthemi pectate lyase C (PelC), the primary sequence alignment between the pectate and pectin lyase subfamilies has been corrected and the active site region for the pectin lyases deduced. The substrate-binding site in PLB is considerably less hydrophilic than the comparable PelC region and consists of an extensive network of highly conserved Trp and His residues. The PLB structure provides an atomic explanation for the lack of a catalytic requirement for Ca2+ in the pectin lyase family, in contrast to that found in the pectate lyase enzymes. Surprisingly, however, the PLB site analogous to the Ca2+ site in PelC is filled with a positive charge provided by a conserved Arg in the pectin lyases. The significance of the finding with regard to the enzymatic mechanism is discussed.

The Role of Citizen Participation in Wildlife-Sensitive Transportation Projects

An extensive and growing road system in the United States bisects vital wildlife habitat and is causing deleterious ecological effects on many wildlife species. The primary impacts include collisions between wildlife and vehicles, altered movement patterns within habitat, and/or the complete blockage of movements between vital habitats. The increasing size of the road network and number of vehicles will only intensify the problem unless proactive wildlife mitigation measures are developed to minimize these adverse effects. Therefore, this capstone project examines the role of citizen advocacy for promoting wildlife protection in the planning and development of wildlife-sensitive transportation projects in the United States. Based upon a data analysis of 21 questionnaires from qualified participants, it was determined that citizen participation is an important component associated with the development of wildlife-sensitive transportation projects. However, four major barriers to facilitating effective citizen participation processes were identified. 1) A lack of awareness. Citizens are only minimally aware of wildlife and transportation issues, including: a) the ecological impacts of roads, b) the solutions available to mitigate these impacts, and c) the opportunities to advocate for the protection of wildlife during transportation planning processes; 2) Public apathy or a lack of citizen interest in wildlife and transportation issues; 3) Ineffective citizen participation techniques and processes; and 4) Poor communication with citizens. Four recommendations were provided to assist in overcoming these barriers and to help define a better role for citizen advocacy in protecting wildlife from the growing road network.

Evolution of Posidonia oceanica seagrass meadows and its implications for management

Results of the monitoring network of the Posidonia oceanica meadows in the Valencia region in Spain are analysed. For spatial comparison the whole data set has been analysed, however, for temporal trends we only selected stations that have been monitored at least 6 years in the period of 2002–2011 (26 stations in 13 localities). At the south of the studied area, meadows are larger, and they have higher density and covering than that in the Valencia Gulf, excluding Oropesa meadow. Monitoring of P. oceanica meadows in the Valencia region in Spain indicates that most of them are stationary or they are increasing their density and covering while no decline was observed in the studied meadows. These results indicate that there is not a general decline of P. oceanica meadows and that the decline of P. oceanica, when it has been observed in other studies, is produced by local causes that may be managed at the local level. This study also reflects the importance of long series of direct data to analyse trends in the population dynamics for slow-growing species.

Applying model-driven engineering to the development of Rich Internet Applications for Business Intelligence

Business Intelligence (BI) applications have been gradually ported to the Web in search of a global platform for the consumption and publication of data and services. On the Internet, apart from techniques for data/knowledge management, BI Web applications need interfaces with a high level of interoperability (similar to the traditional desktop interfaces) for the visualisation of data/knowledge. In some cases, this has been provided by Rich Internet Applications (RIA). The development of these BI RIAs is a process traditionally performed manually and, given the complexity of the final application, it is a process which might be prone to errors. The application of model-driven engineering techniques can reduce the cost of development and maintenance (in terms of time and resources) of these applications, as they demonstrated by other types of Web applications. In the light of these issues, the paper introduces the Sm4RIA-B methodology, i.e., a model-driven methodology for the development of RIA as BI Web applications. In order to overcome the limitations of RIA regarding knowledge management from the Web, this paper also presents a new RIA platform for BI, called RI@BI, which extends the functionalities of traditional RIAs by means of Semantic Web technologies and B2B techniques. Finally, we evaluate the whole approach on a case study—the development of a social network site for an enterprise project manager.

A GIS-based methodology to quantitatively define an Adjacent Protected Area in a shallow karst cavity: The case of Altamira cave

Different types of land use are usually present in the areas adjacent to many shallow karst cavities. Over time, the increasing amount of potentially harmful matter and energy, of mainly anthropic origin or influence, that reaches the interior of a shallow karst cavity can modify the hypogeal ecosystem and increase the risk of damage to the Palaeolithic rock art often preserved within the cavity. This study proposes a new Protected Area status based on the geological processes that control these matter and energy fluxes into the Altamira cave karst system. Analysis of the geological characteristics of the shallow karst system shows that direct and lateral infiltration, internal water circulation, ventilation, gas exchange and transmission of vibrations are the processes that control these matter and energy fluxes into the cave. This study applies a comprehensive methodological approach based on Geographic Information Systems (GIS) to establish the area of influence of each transfer process. The stratigraphic and structural characteristics of the interior of the cave were determined using 3D Laser Scanning topography combined with classical field work, data gathering, cartography and a porosity–permeability analysis of host rock samples. As a result, it was possible to determine the hydrogeological behavior of the cave. In addition, by mapping and modeling the surface parameters it was possible to identify the main features restricting hydrological behavior and hence direct and lateral infiltration into the cave. These surface parameters included the shape of the drainage network and a geomorphological and structural characterization via digital terrain models. Geological and geomorphological maps and models integrated into the GIS environment defined the areas involved in gas exchange and ventilation processes. Likewise, areas that could potentially transmit vibrations directly into the cave were identified. This study shows that it is possible to define a Protected Area by quantifying the area of influence related to each transfer process. The combined maximum area of influence of all the processes will result in the new Protected Area. This area will thus encompass all the processes that account for most of the matter and energy carried into the cave and will fulfill the criteria used to define the Protected Area. This methodology is based on the spatial quantification of processes and entities of geological origin and can therefore be applied to any shallow karst system that requires protection.

Impedance spectroscopy study of the effect of environmental conditions in the microstructure development of OPC and slag cement mortars

In this work, the microstructure of mortars made with an ordinary Portland cement and slag cement has been studied. These mortars were exposed to four different constant temperature and relative humidity environments during a 180-day period. The microstructure has been studied using impedance spectroscopy, and mercury intrusion porosimetry as a contrast technique. The impedance spectroscopy parameters make it possible to analyze the evolution of the solid fraction formation for the studied mortars and their results are confirmed with those obtained using mercury intrusion porosimetry. The development of the pore network of mortars is affected by the environment. However, slag cement mortars are more influenced by temperature while the relative humidity has a greater influence on the OPC mortars. The results show that slag cement mortars hardened under non-optimal environments have a more refined microstructure than OPC mortars for the studied environmental conditions.

Industries and Citizens’ Groups Networks in EU Food Policy: The Emergence of ‘Unholy Alliances’ in Multilevel Governance? Brugges Political Research Paper No. 30, September 2013

Food policy is one the most regulated policy fields at the EU level. ‘Unholy alliances’ are collaborative patterns that temporarily bring together antagonistic stakeholders behind a common cause. This paper deals with such ‘transversal’ co-operations between citizens’ groups (NGOs, consumers associations…) and economic stakeholders (food industries, retailers…), focusing on their ambitions and consequences. This paper builds on two case studies that enable a more nuanced view on the perspectives for the development of transversal networks at the EU level. The main findings are that (i) the rationale behind the adoption of collaborative partnerships actually comes from a case-by-case cost/benefit analysis leading to hopes of improved access to institutions; (ii) membership of a collaborative network leads to a learning process closely linked to the network’s performance; and (iii) coalitions can have a better reception — rather than an automatic better access — depending on several factors independent of the stakeholders themselves.

Neurogenomic mechanisms of social plasticity

Group-living animals must adjust the expression of their social behaviour to changes in their social environment and to transitions between life-history stages, and this social plasticity can be seen as an adaptive trait that can be under positive selection when changes in the environment outpace the rate of genetic evolutionary change. Here, we propose a conceptual framework for understanding the neuromolecular mechanisms of social plasticity. According to this framework, social plasticity is achieved by rewiring or by biochemically switching nodes of a neural network underlying social behaviour in response to perceived social information. Therefore, at the molecular level, it depends on the social regulation of gene expression, so that different genomic and epigenetic states of this brain network correspond to different behavioural states, and the switches between states are orchestrated by signalling pathways that interface the social environment and the genotype. Different types of social plasticity can be recognized based on the observed patterns of inter- versus intra-individual occurrence, time scale and reversibility. It is proposed that these different types of social plasticity rely on different proximate mechanisms at the physiological, neural and genomic level.

Epileptic networks are strongly connected with and without the effects of interictal discharges

OBJECTIVE Epilepsy is increasingly considered as the dysfunction of a pathologic neuronal network (epileptic network) rather than a single focal source. We aimed to assess the interactions between the regions that comprise the epileptic network and to investigate their dependence on the occurrence of interictal epileptiform discharges (IEDs). METHODS We analyzed resting state simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) recordings in 10 patients with drug-resistant focal epilepsy with multifocal IED-related blood oxygen level-dependent (BOLD) responses and a maximum t-value in the IED field. We computed functional connectivity (FC) maps of the epileptic network using two types of seed: (1) a 10-mm diameter sphere centered in the global maximum of IED-related BOLD map, and (2) the independent component with highest correlation to the IED-related BOLD map, named epileptic component. For both approaches, we compared FC maps before and after regressing out the effect of IEDs in terms of maximum and mean t-values and percentage of map overlap. RESULTS Maximum and mean FC maps t-values were significantly lower after regressing out IEDs at the group level (p < 0.01). Overlap extent was 85% ± 12% and 87% ± 12% when the seed was the 10-mm diameter sphere and the epileptic component, respectively. SIGNIFICANCE Regions involved in a specific epileptic network show coherent BOLD fluctuations independent of scalp EEG IEDs. FC topography and strength is largely preserved by removing the IED effect. This could represent a signature of a sustained pathologic network with contribution from epileptic activity invisible to the scalp EEG.

Development of procedures for assessing the impact of vocational education research and development on vocational education (Project IMPACT).

Funding agreement no.: R-31-20-X-0141-166.

European Elites and the Idea of Europe after the End of Empire /

A study of the genesis of ‘European civilisation’ as a concept of 20th-C EU political practice & as a specific project of a transnational network of EU elites, examining how they sought to rehabilitate EU identity as a response to a crisis of belonging following the 1917-1920 revolutions & the collapse of the Hohenzollern, Habsburg & RU Empires.

The composition of attachment networks throughout the adult years

This study assessed the structure of adults' attachment networks, using a questionnaire measure of preferred attachment figures with a large sample of adults (N = 812) representing various ages and life situations. Two broad research questions were addressed. The first question concerned the variety of attachment figures reported by adults and the relative strength of attachment to each, including preferred (primary) attachment figures. The second question concerned the effects of normative life events on attachment networks and the nature of primary attachment figures in different life situations. Overall, the results supported the preeminent role of attachment relationships with romantic partners. However, relationships with mothers, fathers, siblings, children, and friends also met the strict criteria used to define full-blown attachments; further, each of these targets constituted the primary attachment figure for some participants. The structure of the attachment network was related to variables such as age, relationship status, and parental status, attesting to the important role of normative life events. The results have theoretical and applied significance and are related to principles of attachment, caregiving, and socioemotional selectivity.