Descripción: Concentration gradients inside cells are involved in key processes such as cell division and morphogenesis. Here we show that a model of the enzymatic step catalized by phosphofructokinase (PFK), a step which is responsible for the appearance of homogeneous oscillations in the glycolytic pathway, displays Turing patterns with an intrinsic length-scale that is smaller than a typical cell size. All the parameter values are fully consistent with classic experiments on glycolytic oscillations and equal diffusion coefficients are assumed for ATP and ADP. We identify the enzyme concentration and the glycolytic flux as the possible regulators of the pattern. To the best of our knowledge, this is the first closed example of Turing pattern formation in a model of a vital step of the cell metabolism, with a built-in mechanism for changing the diffusion length of the reactants, and with parameter values that are compatible with experiments. Turing patterns inside cells could provide a check-point that combines mechanical and biochemical information to trigger events during the cell division process. © 2007 Strier, Ponce Dawson.

Descripción: A paleomagnetic study, carried out on 9 sites of the La Flecha Formation (facies Los Sapitos, Upper Cambrian, Marjuman-Steptoean) exposed along the la Angostura creek, Precordillera of La Rioja (29.5°S, 68.7°W), permitted to determine two magnetic components. One is postectonic and of low coercivities and unblocking temperatures (A, Dec: 7.5°, Inc: -40.3°, a95: 10.1°, N: 6), being interpreted as a recent remanence of probable viscous origin. A second, pretectonic, component was isolated in seven sites with opposite polarities and is likely carried by magnetite (B, Dec: 206.9°, Inc: 63.3°, a95: 12.8°, N: 7). The paleomagnetic pole position for this component (Lat: 63.8°S, Long: 244.6°E, dp: 15.9°, dm: 20.2°) suggests that the remanence was acquired by the end of the Permian and it is interpreted as produced by the regional remagnetization associated with the San Rafael orogenic phase found in other units of the Precordillera. An analysis of pole positions, type of magnetizations, polarities and geographic distribution of the remagnetized units suggests a pattern of time-space migration of the remagnetization from west to east, between the Early Permian and the Permian-Triassic. This pattern is consistent with a model of remagnetization by migration of fluids expelled from the orogenic area that reached rocks not involved directly in the deformation. The pole position obtained for La Flecha Formation also suggests the lack of major tectonic rotations in the study area since the Permian. © 2005 Asociación Geológica Argentina.

Descripción: Ciénaga del Río Huaco Formation was deposited during the Cretaceous in the Precordillera Central (La Rioja and San Juan provinces). The unit forms part of a thick red-bed sequence including rocks of different ages (from Late Paleozoic to Tertiary) and problematic identification. In the La Troya river area, the red bed sequence is composed of the Panacán (Permian), Santo Domingo (Late Triassic- Early Jurassic), Ciénaga del Río Huaco (Cretaceous) and Puesto La Flecha Formations (Oligocene- Early Nfiocene). In the past, all these formations were included in the same stratigrapbic unit and only in recent years the different formations could be separated mainly based on their fossil contain. In the case of Ciénaga del Rio Huaco Formation, the finding of microfossils (palynomorphs and ostracods) allowed to infer a Late Cretaceous age for these rocks. However, a radiometric age of 108,1 ± 4,4 Ma presented in this paper, clearly suggest that the unit was deposited at the end of the Early Cretaceous. This age is the first Cretaceous absolute age in the Precordillera Central and enhances the time constraints of of the Cretaceous Basin.

Descripción: The study area is located in central-western Santa Cruz including El Chaltén town between 49°00'and 49°36'S - 73°30'and 72°00'W. Environmental variability, relief, parent material, altitude, climate, vegetation and soils were recognized. According to characteristics of the soils, it is possible to differentiate three sectors: western, central and eastern. Inceptisols, Spodosols and Andisols dominate in the first, meanwhile in Central area the main soils are Molisolls and Entisols. Aridisols and aridic Entisols dominate in the Eastern sector. A west-east variation trend, in relation to soil features could be established: an increase in pH, CEC, exchangeable bases and % of CaCO3. Inversely there is an increase % C, pHNaF (in udic regime soils) and divalent/monovalent cations relationship.

Descripción: The high levels of δ-aminolevulinate synthetase (ALA-S) in Rhodopseudomonas palustris cells grown anaerobically in the light (Ph) decrease to those found in cells grown aerobically in the dark (A), when the former cultures were vigorously oxygenated; simultaneously bacteriochlorophyll (Bchl) synthesis abruptly halted leading to diminished steady-state specific Bchl content. When flushing oxygen was interrupted, enzymic activity increased, whether chloramphenicol was present or not in the medium; if the protein synthesis inhibitor was added when oxygenation started, ALA-S declined in the same fashion as in its absence, but thereafter reactivation of the enzyme was lower than before. Succinyl-CoA-synthetase and ALA-dehydratase activities were also measured under the conditions described, and no changes at all have been observed. The existence of different forms of ALA-S in R. palustris depending on growth conditions is postulated along with the formation of low molecular weight factors which can modulate ALA-S activity by binding to the enzyme; a widespread mechanism in the adaptation of micro-organisms to changes in environment. It is also proposed that this particular regulatory phenomenon, could be referred to as a switch off/on mechanism controlling ALA-S activity in R. palustris. © 1987.

Descripción: Stress granules (SGs) and P-bodies (PBs) are related cytoplasmic structures harboring silenced mRNAs. SGs assemble transiently upon cellular stress, whereas PBs are constitutive and are further induced by stress. Both foci are highly dynamic, with messenger ribonucleoproteins (mRNPs) and proteins rapidly shuttling in and out. Here, we show that impairment of retrograde transport by knockdown of mammalian dynein heavy chain 1 (DHC1) or bicaudal D1 (BicD1) inhibits SG formation and PB growth upon stress, without affecting proteinsynthesis blockage. Conversely, impairment of anterograde transport by knockdown of kinesin-1 heavy chain (KIF5B) or kinesin light chain 1 (KLC1) delayed SG dissolution. Strikingly, SG dissolution is not required to restore translation. Simultaneous knockdown of dynein and kinesin reverted the effect of single knockdowns on both SGs and PBs, suggesting that a balance between opposing movements driven by these molecular motors governs foci formation and dissolution. Finally, we found that regulation of SG dynamics by dynein and kinesin is conserved in Drosophila.

Descripción: The previous analysis of the prehistoric slide phenomena in the main Andes of Neuquén Province in Argentina (36o-38oS), triggered the study of those located south of this la-titude. Therefore a new set of mass wasting deposits has been identified, whose trigger factors and corresponding tectonic framework, where they are located, differ from the northern slides. Their study was performed in three specific areas: Aluminé, Chapelco and Arroyo Limay Chico. Earth flows predominate in relation to slumps. The only exception is the Chapelco rock avalanche. Their occurrence seems to be related to the presence of Limay Chico member of the Caleufú Formation, whose lithology (expanding clays), particular rheology before water saturation, and particular disposition underlying basaltic lava and conglomeradic plains were conditioning factors. The trigger factor of the Present and prehistoric earth flows has been intense orographic precipitations. Water saturation reduced friction and cohesion in materials, incrementing water pore pressure and producing slope instabilities. Rotational slides are related to the slope basal erosion produced by lateral river migration and additionally to precipitations. Slope orientation has been important in determining location of main slides. Lateral slope release through the flanks of glacial valleys due to debutressing because of the glacial retire in the area, has produced instability and rock fracturation that led to slide phenomena. The Chapelco rock avalanche is particularly related to copious precipitations during postglacial times. Thus sliding main trigger factors south of 38oS differ from those pro-posed for the northern area where earthquakes dominated. Their specific age is still unknown, although their geomorphologic analysis allow to constraint a postglacial age for all these occurrences. However, temporal relationships are lacking for the specific case of the arroyo Limay Chico, beyond the glaciated area.

Descripción: FKBP51 and FKBP52 (FK506-binding protein 51 and 52) are tetratricopeptide repeat-domain immunophilins belonging to the tetratricopeptide- protein•hsp90•hsp70•p23 heterocomplex bound to steroid receptors. Immunophilins are related to receptor folding, subcellular localization, and hormonedependent transcription. Also, they bind the immunosuppressant macrolide FK506, which shows neuroregenerative and neuroprotective actions by a still unknown mechanism. In this study, we demonstrate that in both, undifferentiated neuroblastoma cells and embryonic hippocampal neurons, the FKBP52• hsp90•p23 heterocomplex concentrates in a perinuclear structure. Upon cell stimulation with FK506, this structure disassembles and this perinuclear area becomes transcriptionally active. The acquisition of a neuronal phenotype is accompanied by increased expression of bIII-tubulin, Map-2, Tau-1, but also hsp90, hsp70, p23, and FKBP52. During the early differentiation steps, the perinuclear heterocomplex redistributes along the cytoplasm and nascent neurites, p23 binds to intermediate filaments and microtubules acquired higher filamentary organization. While FKBP52 moves towards neurites and concentrates in arborization bodies and terminal axons, FKBP51, whose expression remains constant, replaces FKBP52 in the perinuclear structure. Importantly, neurite outgrowth is favored by FKBP52 over-expression or FKBP51 knock-down, and is impaired by FKBP52 knock-down or FKBP51 over-expression, indicating that the balance between these FK506-binding proteins plays a key role during the early mechanism of neuronal differentiation. © 2010 The Authors.

Descripción: The use of more lipophilic derivatives of 5-aminolevulinic acid (ALA) is expected to have better diffusing properties, and after conversion into the parent ALA, to reach a higher protoporphyrin IX (PPIX) formation rate, thus improving the efficacy of topical photodynamic therapy (PDT). Here we have analysed the behaviour of 3 ALA derivatives (ALA methyl-ester, hexyl ester and a 2-sided derivative) regarding PPIX formation, efficiency in photosensitizing cells and mechanism of cellular death. The maximum amount of porphyrins synthesized from 0.6 mM ALA was 47 ± 8 ng/105 cells. The same amount was formed by a concentration 60-fold lower of hexyl-ALA and 2-fold higher of methyl-ALA. The 2-sided derivative failed to produce PPIX accumulation. Applying a 0.6 J cm-2 light dose, cell viability decreased to 50%. With the 1.5 J cm-2 light dose, less than 20% of the cells survive, and higher light doses produced nearly total cell killing. Comparing the PPIX production and the induced phototoxicity, the more the amount of porphyrins, the greater the cellular killing, and PPIX formed from either ALA or ALA-esters equally sensitize the cells to photoinactivation. ALA-PDT treated cells exhibited features of apoptosis, independently on the pro-photosensitizer employed. ALA-PDT can be improved with the use of ALA derivatives, reducing the amount of ALA necessary to induce efficient photosensitization. © 2001 Cancer Research Campaign.

Descripción: Background: Self-assembly is a common theme in proteins of unrelated sequences or functions. The human papillomavirus E7 oncoprotein is an extended dimer with an intrinsically disordered domain, that can form large spherical oligomers. These are the major species in the cytosol of HPV transformed and cancerous cells. E7 binds to a large number of targets, some of which lead to cell transformation. Thus, the assembly process not only is of biological relevance, but represents a model system to investigate a widely distributed mechanism. Methodology/Principal Findings: Using various techniques, we monitored changes in secondary, tertiary and quaternary structure in a time course manner. By applying a robust kinetic model developed by Zlotnik, we determined the slow formation of a monomeric "Z-nucleus" after zinc removal, followed by an elongation phase consisting of sequential second-order events whereby one monomer is added at a time. This elongation process takes place at a strikingly slow overall average rate of one monomer added every 28 seconds at 20 μM protein concentration, strongly suggesting either a rearrangement of the growing complex after binding of each monomer or the existence of a "conformation editing" mechanism through which the monomer binds and releases until the appropriate conformation is adopted. The oligomerization determinant lies within its small 5 kDa C-terminal globular domain and, remarkably, the E7 N-terminal intrinsically disordered domain stabilizes the oligomer, preventing an insoluble amyloid route. Conclusion: We described a controlled ordered mechanism with features in common with soluble amyloid precursors, chaperones, and other spherical oligomers, thus sharing determining factors for symmetry, size and shape. In addition, such a controlled and discrete polymerization reaction provides a valuable tool for nanotechnological applications. Finally, its increased immunogenicity related to its supramolecular structure is the basis for the development of a promising therapeutic vaccine candidate for treating HPV cancerous lesions. © 2012 Smal et al.

Descripción: Flagella-generated fluid stirring has been suggested to enhance nutrient uptake for sufficiently large micro-organisms, and to have played a role in evolutionary transitions to multicellularity. A corollary to this predicted size-dependent benefit is a propensity for phenotypic plasticity in the flow-generating mechanism to appear in large species under nutrient deprivation. We examined four species of volvocalean algae whose radii and flow speeds differ greatly, with Péclet numbers (Pe) separated by several orders of magnitude. Populations of unicellular Chlamydomonas reinhardtii and one- to eight-celled Gonium pectorale (Pe ∼ 0.1-1) and multicellular Volvox carteri and Volvox barberi (Pe ∼ 100) were grown in diluted and undiluted media. For C. reinhardtii and G. pectorale, decreasing the nutrient concentration resulted in smaller cells, but had no effect on flagellar length and propulsion force. In contrast, these conditions induced Volvox colonies to grow larger and increase their flagellar length, separating the somatic cells further. Detailed studies on V. carteri found that the opposing effects of increasing beating force and flagellar spacing balance, so the fluid speed across the colony surface remains unchanged between nutrient conditions. These results lend further support to the hypothesized link between the Péclet number, nutrient uptake and the evolution of biological complexity in the Volvocales. © 2011 The Royal Society.

Descripción: Small outcrops of biotitic-amphibolic schists and amphibolites found in two localities suggest that the Cushamen Formation is host rock of the Central Patagonian Batholith in Gastre. The characteristics of these rocks were investigated using structural, petrographic, magnetic fabric, and garnet chemical-zonation studies. Garnet is observed as a late product of contact metamorphism. Structural data from the studied area and from other localities in the region are in conflict with models that invoke the occurrence of uniform, large-scale dextral displacements along the Gastre lineament in Mesosoic times. Rather, the data suggest that the Gastre granitoids record heterogeneous low-temperature deformation of likely Late Triassic age. This low-temperature deformation appears as small, localized outcrops, and we suggest that it is related to the accommodation of the successive magma batches that built the Central Patagonian Batholith.

Descripción: The epsins are a family of adaptors involved in recruiting other endocytic proteins, binding of ubiquitylated cargo and induction of membrane curvature. These molecules bear a characteristic epsin N-terminal homology (ENTH) domain and multiple peptide motifs that mediate protein-protein interactions. We have previously demonstrated that the ENTH domain of epsin is involved in Cdc42 signaling regulation. Here, we present evidence that yeast epsin 2 (Ent2) plays a signaling role during cell division. We observed that overexpression of the ENTH domain of Ent2 (ENTH2), but not Ent1, promoted the formation of chains of cells and aberrant septa. This dominant-negative effect resulted from ENTH2-mediated interference with septin assembly pathways. We mapped the ENTH2 determinants responsible for induction of the phenotype and found them to be important for efficient binding to the septin regulatory protein, Bem3. Supporting a physiological role for epsin 2 in cell division, the protein localized to sites of polarized growth and cytokinesis and rescued a defect in cell division induced by Bem3 misregulation. Collectively, our findings provide a potential molecular mechanism linking endocytosis (via epsin 2) with signaling pathways regulating cell division.

Descripción: Triassic clastic and volcanic rocks from the Precordillera were deposited in the Cuyana rift basin filling half-graben systems. Contractional/transpressional Andean tectonics leads to the almost complete inversion of some portions of the basin which resulted in present-day isolated, structurally controlled outcrops of these Triassic rocks. In the Southern Precordillera both the degree of Neogene tectonic inversion and structural compexities are variable. At the regional scale, these variations in Andean deformation are related to first order anisotropies like the Cuyana basin borders and previous shear zones of Permian age (San Rafael orogenic phase). This paper focuses on the kinematic analysis done in the Cerro Manantial thrust sheet area (Cordón San Bartolo, central sector of the South Precordillera) where tectonic inversion was not that strong and the influence of oblique strain zones is practically null. Four sets of extensional/ transtensional faults were recognized affecting Triassic sedimentary rocks of the El Cielo Formation (Uspallata Group) at the Quebrada El Salto. Fault displacements are of decimetric to metric scale. Mesoscopic kinematic indicators (en-échèlon tensional gashes, Riedel shear fractures, sigmoidal fractures) were measured. Once Andean deformation was restored, a NNE direction for the Triassic extension was determined. Considering a northern branch of the Cuyana basin trending NNW (Az. 150°) and oblique to the direction of extension (Az. 35-40°), a sinistral strike-slip component could be inferred for this portion of the basin.

Descripción: In daily life, memories are intertwined events. Little is known about the mechanisms involved in their interactions. Using two hippocampus-dependent (spatial object recognition and contextual fear conditioning) and one hippocampus-independent (conditioned taste aversion) learning tasks, we show that in rats subjected to weak training protocols that induce solely short term memory (STM), long term memory (LTM) is promoted and formed only if training sessions took place in contingence with a novel, but not familiar, experience occurring during a critical time window around training. This process requires newly synthesized proteins induced by novelty and reveals a general mechanism of LTM formation that begins with the setting of a "learning tag" established by a weak training. These findings represent the first comprehensive set of evidences indicating the existence of a behavioral tagging process that in analogy to the synaptic tagging and capture process, need the creation of a transient, protein synthesis-independent, and input specific tag.

Descripción: A highly sulfated 3-linked β-arabinan (Ab1) with arabinose in the pyranose form was obtained from green seaweed Codium vermilara (Bryopsidales). It comprised major amounts of units sulfated on C-2 and C-4 and constitutes the first polysaccharide of this type isolated in the pure form and fully characterized. Ab1 showed anticoagulant activity by global coagulation tests. Less sulfated arabinans obtained from the same seaweed have less or no activity. Ab1 exerts its activity through direct and indirect (antithrombin- and heparin cofactor II-mediated) inhibition of thrombin. Direct thrombin inhibition was studied in detail. By native PAGE, it was possible to detect formation of a complex between Ab1 and human thrombin (HT). Ab1 binding to HT was measured by fluorescence spectroscopy. CD spectra of the Ab1 complex suggested that ligand binding induced a small conformational change on HT. Ab1-thrombin interactions were studied by molecular dynamic simulations using the persulfated octasaccharide as model compound. Most carbohydrate-protein contacts would occur by interaction of sulfate groups with basic amino acid residues on the surface of the enzyme, more than 60% of them being performed by the exosite 2-composing residues. In these interactions, the sulfate groups on C-2 were shown to interact more intensely with the thrombin structure. In contrast, the disulfated oligosaccharide does not promote major conformational modifications at the catalytic site when complexed to exosite 1. These results show that this novel pyranosic sulfated arabinan Ab1 exerts its anticoagulant activity by a mechanism different from those found previously for other sulfated polysaccharides and glycosaminoglycans. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

Descripción: In silico analyses have revealed a conserved protein domain (CHDL) widely present in bacteria that has significant structural similarity to eukaryotic cadherins. A CHDL domain was shown to be present in RapA, a protein that is involved in autoaggregation of Rhizobium cells, biofilm formation, and adhesion to plant roots as shown by us and others. Structural similarity to cadherins suggested calcium-dependent oligomerization of CHDL domains as a mechanistic basis for RapA action. Here we show by circular dichroism spectroscopy, light scattering, isothermal titration calorimetry, and other methods that RapA2 from Rhizobium leguminosarum indeed exhibits a cadherin-like β-sheet conformation and that its proper folding and stability are dependent on the binding of one calcium ion per protein molecule. By further in silico analysis we also reveal that RapA2 consists of two CHDL domains and expand the range of CHDLcontaining proteins in bacteria and archaea. However, light scattering assays at various concentrations of added calcium revealed that RapA2 formed neither homo-oligomers nor hetero-oligomers with RapB (a distinct CHDL protein), indicating that RapA2 does not mediate cellular interactions through a cadherin-like mechanism. Instead, we demonstrate that RapA2 interacts specifically with the acidic exopolysaccharides (EPSs) produced by R. leguminosarum in a calcium-dependent manner, sustaining a role of these proteins in the development of the biofilm matrix made of EPS. Because EPS binding by RapA2 can only be attributed to its two CHDL domains, we propose that RapA2 is a calcium-dependent lectin and thatCHDLdomains in various bacterial and archaeal proteins confer carbohydrate binding activity to these proteins. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

Descripción: The Jurassic history of southern South America shows a complex geologic evolution which is the result of different processes that began along the western Gondwana margin during the initial stages of Pangea breakup. Andean subduction along the Pacific continental margin began in the Early Jurassic, after a period of continental-scale extension and rifting, which peaked by the end of the Triassic in central and northern Argentina and Chile. Renewal of subduction was the result of an episode of ocean growth along a series of spreading centers between North and South America when the separation of these continents began as a consequence of the activity of the Central Atlantic Magmatic Province hotspot. Motion along these spreading centers produced a component of oblique, SE-directed subduction along the western margin of South America and the reactivation of inherited orthogonal structural features as the N70°E trending Huincul ridge in the Neuquén Basin that was uplifted during Jurassic times. Subduction along the north-south trending Argentine-Chilean continental margin acelerated during the break-up between West and East Gondwana soon after the opening of the Indian Ocean, linked to the Karoo hot-spot. Subduction took place under extensional conditions probably associated with a negative trench roll-back, leading to the formation of a magmatic arc along the Coast Ranges from southern Peru to central Chile and, to the east, the Arequipa, Tarapacá and Neuquén extensional back-arc basins. In northern Patagonia, early Jurassic arc related magmatism occurred to the east of the present day Andean Cordillera along the short-lived (190-170 Ma) Subcordilleran Batholith and the associated Liassic intra arc basin. Arc magmatism ceased in northern Patagonia at ca 170 Ma to be replaced by huge volumes of Early to Middle Jurassic rhyolites and dacites of the Chon-Aike Large Igneous province produced as a result of crustal melting in an overheated crust during the initial stages of Gondwana breakup. Early rifting during Middle-Late Jurassic times took place in the Cañadón Asfalto Basin and the Late Jurassic Río Guenguel, Río Mayo and Río Senguerr basins, orthogonal to the continental margin as a consequence of the Weddell Sea opening. Acid magmatism was associated with widespread extension and culminated in the opening of the ocean-floored Rocas Verdes Basin. The causes of the cessation of magmatism in the Subcordilleran Batholith, the origin of the Chon Aike LIP and the rotation of the magmatic front towards the Patagonian Batholith around 150 Ma are still not well understood. Hypothesis linking this mutating tectonic scenario to the collision of exotic terranes against the Pacific margin of Patagonia during the early to middle Jurassic should be taken into consideration.

Descripción: Stress granules are cytoplasmic mRNA-silencing foci that form transiently during the stress response. Stress granules harbor abortive translation initiation complexes and are in dynamic equilibrium with translating polysomes. Mammalian Staufen 1 (Stau1) is a ubiquitous double-stranded RNA-binding protein associated with polysomes. Here, we show that Stau1 is recruited to stress granules upon induction of endoplasmic reticulum or oxidative stress as well in stress granules induced by translation initiation blockers. We found that stress granules lacking Stau1 formed in cells depleted of this molecule, indicating that Stau1 is not an essential component of stress granules. Moreover, Stau1 knockdown facilitated stress granule formation upon stress induction. Conversely, transient transfection of Stau1 impaired stress granule formation upon stress or pharmacological initiation arrest. The inhibitory capacity of Stau1 mapped to the amino-terminal half of the molecule, a region known to bind to polysomes. We found that the fraction of polysomes remaining upon stress induction was enriched in Stau1, and that Stau1 overexpression stabilized polysomes against stress. We propose that Stau1 is involved in recovery from stress by stabilizing polysomes, thus helping stress granule dissolution.