Evolution and cellular function of monothiol glutaredoxins: involvement in iron-sulphur cluster assembly

A number of bacterial species, mostly proteobacteria, possess monothiol glutaredoxins homologous to the Saccharomyces cerevisiae mitochondrial protein Grx5, which is involved in iron–sulphur cluster synthesis. Phylogenetic profiling is used to predict that bacterial monothiol glutaredoxins also participate in the iron–sulphur cluster (ISC) assembly machinery, because their phylogenetic profiles are similar to the profiles of the bacterial homologues of yeast ISC proteins. High evolutionary cooccurrence is observed between the Grx5 homologues and the homologues of the Yah1 ferredoxin, the scaffold proteins Isa1 and Isa2, the frataxin protein Yfh1 and the Nfu1 protein. This suggests that a specific functional interaction exists between these ISC machinery proteins. Physical interaction analyses using low-definition protein docking predict the formation of strong and specific complexes between Grx5 and several components of the yeast ISC machinery. Two-hybrid analysis has confirmed the in vivo interaction between Grx5 and Isa1. Sequence comparison techniques and cladistics indicate that the other two monothiol glutaredoxins of S. cerevisiae, Grx3 and Grx4, have evolved from the fusion of a thioredoxin gene with a monothiol glutaredoxin gene early in the eukaryotic lineage, leading to differential functional specialization. While bacteria do not contain these chimaeric glutaredoxins, in many eukaryotic species Grx5 and Grx3/4-type monothiol glutaredoxins coexist in the cell.

Signaling across the synapse: a role for Wnt and Dishevelled in presynaptic assembly and neurotransmitter release

Proper dialogue between presynaptic neurons and their targets is essential for correct synaptic assembly and function. At central synapses, Wnt proteins function as retrograde signals to regulate axon remodeling and the accumulation of presynaptic proteins. Loss of Wnt7a function leads to defects in the localization of presynaptic markers and in the morphology of the presynaptic axons. We show that loss of function of Dishevelled-1 (Dvl1) mimics and enhances the Wnt7a phenotype in the cerebellum. Although active zones appear normal, electrophysiological recordings in cerebellar slices from Wnt7a/Dvl1 double mutant mice reveal a defect in neurotransmitter release at mossy fi ber–granule cell synapses. Deficiency in Dvl1 decreases, whereas exposure to Wnt increases, synaptic vesicle recycling in mossy fi bers. Dvl increases the number of Bassoon clusters, and like other components of the Wnt pathway, it localizes to synaptic sites. These fi ndings demonstrate that Wnts signal across the synapse on Dvl-expressing presynaptic terminals to regulate synaptic assembly and suggest a potential novel function for Wnts in neurotransmitter release.

Interplay between surface anisotropy and dipolar interactions in an assembly of nanomagnets

We study the interplay between the effects of surface anisotropy and dipolar interactions in monodisperse assemblies of nanomagnets with oriented anisotropy. We derive asymptotic formulas for the assembly magnetization, taking into account temperature, applied field, core and surface anisotropy, and dipolar interparticle interactions. We find that the interplay between surface anisotropy and dipolar interactions is well described by the analytical expression of the assembly magnetization derived here: the overall sign of the product of the two parameters governing the surface and the dipolar contributions determines whether intrinsic and collective terms compete or have synergistic effects on the magnetization. This is illustrated by the magnetization curves of γ-Fe2O3 nanoparticle assemblies in the low concentration limit.

The Human Acid-Sensing Ion Channel ASIC1a: Evidence for a Homotetrameric Assembly State at the Cell Surface.

The chicken acid-sensing ion channel ASIC1 has been crystallized as a homotrimer. We address here the oligomeric state of the functional ASIC1 in situ at the cell surface. The oligomeric states of functional ASIC1a and mutants with additional cysteines introduced in the extracellular pore vestibule were resolved on SDS-PAGE. The functional ASIC1 complexes were stabilized at the cell surface of Xenopus laevis oocytes or CHO cells either using the sulfhydryl crosslinker BMOE, or sodium tetrathionate (NaTT). Under these different crosslinking conditions ASIC1a migrates as four distinct oligomeric states that correspond by mass to multiples of a single ASIC1a subunit. The relative importance of each of the four ASIC1a oligomers was critically dependent on the availability of cysteines in the transmembrane domain for crosslinking, consistent with the presence of ASIC1a homo-oligomers. The expression of ASIC1a monomers, trimeric or tetrameric concatemeric cDNA constructs resulted in functional channels. The resulting ASIC1a complexes are resolved as a predominant tetramer over the other oligomeric forms, after stabilization with BMOE or NaTT and SDS-PAGE/western blot analysis. Our data identify a major ASIC1a homotetramer at the surface membrane of the cell expressing functional ASIC1a channel.

IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs.

The series of events leading to tertiary lymphoid organ (TLO) formation in mucosal organs following tissue damage remain unclear. Using a virus-induced model of autoantibody formation in the salivary glands of adult mice, we demonstrate that IL-22 provides a mechanistic link between mucosal infection, B-cell recruitment, and humoral autoimmunity. IL-22 receptor engagement is necessary and sufficient to promote differential expression of chemokine (C-X-C motif) ligand 12 and chemokine (C-X-C motif) ligand 13 in epithelial and fibroblastic stromal cells that, in turn, is pivotal for B-cell recruitment and organization of the TLOs. Accordingly, genetic and therapeutic blockade of IL-22 impairs and reverses TLO formation and autoantibody production. Our work highlights a critical role for IL-22 in TLO-induced pathology and provides a rationale for the use of IL-22-blocking agents in B-cell-mediated autoimmune conditions.

Approximate Bayesian Computation Reveals the Crucial Role of Oceanic Islands for the Assembly of Continental Biodiversity.

The perceived low levels of genetic diversity, poor interspecific competitive and defensive ability, and loss of dispersal capacities of insular lineages have driven the view that oceanic islands are evolutionary dead ends. Focusing on the Atlantic bryophyte flora distributed across the archipelagos of the Azores, Madeira, the Canary Islands, Western Europe, and northwestern Africa, we used an integrative approach with species distribution modeling and population genetic analyses based on approximate Bayesian computation to determine whether this view applies to organisms with inherent high dispersal capacities. Genetic diversity was found to be higher in island than in continental populations, contributing to mounting evidence that, contrary to theoretical expectations, island populations are not necessarily genetically depauperate. Patterns of genetic variation among island and continental populations consistently fitted those simulated under a scenario of de novo foundation of continental populations from insular ancestors better than those expected if islands would represent a sink or a refugium of continental biodiversity. We, suggest that the northeastern Atlantic archipelagos have played a key role as a stepping stone for transoceanic migrants. Our results challenge the traditional notion that oceanic islands are the end of the colonization road and illustrate the significant role of oceanic islands as reservoirs of novel biodiversity for the assembly of continental floras.

Identification of the regions involved in phonological assembly using a novel paradigm.

Here we adopt a novel strategy to investigate phonological assembly. Participants performed a visual lexical decision task in English in which the letters in words and letterstrings were delivered either sequentially (promoting phonological assembly) or simultaneously (not promoting phonological assembly). A region of interest analysis confirmed that regions previously associated with phonological assembly, in studies contrasting different word types (e.g. words versus pseudowords), were also identified using our novel task that controls for a number of confounding variables. Specifically, the left pars opercularis, the superior part of the ventral precentral gyrus and the supramarginal gyrus were all recruited more during sequential delivery than simultaneous delivery, even when various psycholinguistic characteristics of the stimuli were controlled. This suggests that sequential delivery of orthographic stimuli is a useful tool to explore how readers, with various levels of proficiency, use sublexical phonological processing during visual word recognition.

Supramolecular Gold Metallogelators: The Key Role of Metallophilic Interactions

Gold metallogelators is an emerging area of research. The number of results published in the literature is still scarce. The majority of these gels is observed in organic solvents, and the potential applications are still to be explored. In this work, we present an overview about gold metallogelators divided in two different groups depending on the type of solvent used in the gelation process (organogelators and hydrogelators). A careful analysis of the data shows that aurophilic interactions are a common motif directly involved in gelation involving Au(I) complexes. There are also some Au(III) derivatives able to produce gels but in this case the organic ligands determine the aggregation process. A last section is included about the potential applications that have been reported until now with this new and amazing class of supramolecular assemblies.

Anisotropic surface properties of micro/nanostructured a-C:H:F thin films with self-assembly applications

The singular properties of hydrogenated amorphous carbon (a-C:H) thin filmsdeposited by pulsed DC plasma enhanced chemical vapor deposition (PECVD), such as hardness and wear resistance, make it suitable as protective coating with low surface energy for self-assembly applications. In this paper, we designed fluorine-containing a-C:H (a-C:H:F) nanostructured surfaces and we characterized them for self-assembly applications. Sub-micron patterns were generated on silicon through laser lithography while contact angle measurements, nanotribometer, atomic force microscopy (AFM), and scanning electron microscopy (SEM) were used to characterize the surface. a-C:H:F properties on lithographied surfaces such as hydrophobicity and friction were improved with the proper relative quantity of CH4 and CHF3 during deposition, resulting in ultrahydrophobic samples and low friction coefficients. Furthermore, these properties were enhanced along the direction of the lithographypatterns (in-plane anisotropy). Finally, self-assembly properties were tested with silicananoparticles, which were successfully assembled in linear arrays following the generated patterns. Among the main applications, these surfaces could be suitable as particle filter selector and cell colony substrate.

Assembly Methods of Permanent Magnets for Synchronous Generators

This thesis examines and explains the procedure used to redesign the attachment of permanent magnets to the surface of the rotor of a synchronous generator. The methodology followed to go from the actual assembly to converge to the final purposed innovation was based on the systematic approach design. This meant that first a series of steps had to be predefined as a frame of reference later to be used to compare and select proposals, and finally to obtain the innovation that was sought. Firstly, a series of patents was used as the background for the upcoming ideas. To this end, several different patented assemblies had been found and categorized according the main element onto which this thesis if focused, meaning the attachment element or method. After establishing the technological frame of reference, a brainstorm was performed to obtain as many ideas as possible. Then these ideas were classified, regardless of their degree of complexity or usability, since at this time the quantity of the ideas was the important issue. Subsequently, they were compared and evaluated from different points of view. The comparison and evaluation in this case was based on the use of a requirement list, which established the main needs that the design had to fulfill. Then the selection could be done by grading each idea in accordance with these requirements. In this way, one was able to obtain the idea or ideas that best fulfilled these requirements. Once all of the ideas were compared and evaluated, the best or most suitable idea or ideas were separated. Finally, the selected idea or ideas was/were analyzed in extension and a number of improvements were made. Consequently, a final idea was refined and made more suitable at its performance, manufacture, and life cycle assessment. Therefore, in the end, the design process gave a solution to the problem pointed out at the beginning.

Estratégia supramolecular para a nanotecnologia

Brazilian science is evolving rapidly and steadly in the last 10 years, reaching the 15º place in the international ranking. Research in nanotechnology is following a similar way generating new scientific and technological knowledge in several frontiers but specially in the interfaces of two or more areas, where Chemistry is consolidating itself as a central science. In this context, the supramolecular approach is a very promissing one because it allows the build-up of a chemical inteligence using all the sistematized knowledge for the design and development of new nanomaterials and products. The great challenge of Chemistry is not decrease the dimensionality of the materials but instead find ways to increase the dimensionality and structural complexity keeping strict control on the interactions between the components, in order to generate materials with new properties and functionalities. Unfortunately, the current vigorous advancement of scientific research has not been followed by the transformation of such know-how into patents and produts. Therefore much efforts should be devoted to build a national science and technology program, joining all the segments of the society involved in the technological development (university, institutes of technological research, industry and government) in order to promote the furtherance of the Brazilian technological base. Only in this way it is possible to evolve to a technological society capable to transform the scientific knowledge into wealthy, thus sustaining the socioeconomic development of the country.

Novel Robot Solutions for Carrying out Field Joint Welding and Machining in the Assembly of the Vacuum Vessel of ITER

It is necessary to use highly specialized robots in ITER (International Thermonuclear Experimental Reactor) both in the manufacturing and maintenance of the reactor due to a demanding environment. The sectors of the ITER vacuum vessel (VV) require more stringent tolerances than normally expected for the size of the structure involved. VV consists of nine sectors that are to be welded together. The vacuum vessel has a toroidal chamber structure. The task of the designed robot is to carry the welding apparatus along a path with a stringent tolerance during the assembly operation. In addition to the initial vacuum vessel assembly, after a limited running period, sectors need to be replaced for repair. Mechanisms with closed-loop kinematic chains are used in the design of robots in this work. One version is a purely parallel manipulator and another is a hybrid manipulator where the parallel and serial structures are combined. Traditional industrial robots that generally have the links actuated in series are inherently not very rigid and have poor dynamic performance in high speed and high dynamic loading conditions. Compared with open chain manipulators, parallel manipulators have high stiffness, high accuracy and a high force/torque capacity in a reduced workspace. Parallel manipulators have a mechanical architecture where all of the links are connected to the base and to the end-effector of the robot. The purpose of this thesis is to develop special parallel robots for the assembly, machining and repairing of the VV of the ITER. The process of the assembly and machining of the vacuum vessel needs a special robot. By studying the structure of the vacuum vessel, two novel parallel robots were designed and built; they have six and ten degrees of freedom driven by hydraulic cylinders and electrical servo motors. Kinematic models for the proposed robots were defined and two prototypes built. Experiments for machine cutting and laser welding with the 6-DOF robot were carried out. It was demonstrated that the parallel robots are capable of holding all necessary machining tools and welding end-effectors in all positions accurately and stably inside the vacuum vessel sector. The kinematic models appeared to be complex especially in the case of the 10-DOF robot because of its redundant structure. Multibody dynamics simulations were carried out, ensuring sufficient stiffness during the robot motion. The entire design and testing processes of the robots appeared to be complex tasks due to the high specialization of the manufacturing technology needed in the ITER reactor, while the results demonstrate the applicability of the proposed solutions quite well. The results offer not only devices but also a methodology for the assembly and repair of ITER by means of parallel robots.

A química supramolecular de complexos pirazólicos

The purpose of this review is to describe the progress in the supramolecular chemistry of the pyrazolyl-based metal complexes. The text is written under the structural point of view, emphasizing the role of the covalent and non-covalent interactions in the rational construction of super and supramolecules.