Localization of the K+ Lock-in and the Ba2+ Binding Sites in a Voltage-Gated Calcium-Modulated Channel: Implications for Survival of K+ Permeability

Using Ba2+ as a probe, we performed a detailed characterization of an external K+ binding site located in the pore of a large conductance Ca2+-activated K+ (BKCa) channel from skeletal muscle incorporated into planar lipid bilayers. Internal Ba2+ blocks BKCa channels and decreasing external K+ using a K+ chelator, (+)-18-Crown-6-tetracarboxylic acid, dramatically reduces the duration of the Ba2+-blocked events. Average Ba2+ dwell time changes from 10 s at 10 mM external K+ to 100 ms in the limit of very low [K+]. Using a model where external K+ binds to a site hindering the exit of Ba2+ toward the external side (Neyton, J., and C. Miller. 1988. J. Gen. Physiol. 92:549–568), we calculated a dissociation constant of 2.7 μM for K+ at this lock-in site. We also found that BKCa channels enter into a long-lasting nonconductive state when the external [K+] is reduced below 4 μM using the crown ether. Channel activity can be recovered by adding K+, Rb+, Cs+, or NH4 + to the external solution. These results suggest that the BKCa channel stability in solutions of very low [K+] is due to K+ binding to a site having a very high affinity. Occupancy of this site by K+ avoids the channel conductance collapse and the exit of Ba2+ toward the external side. External tetraethylammonium also reduced the Ba2+ off rate and impeded the channel from entering into the long-lasting nonconductive state. This effect requires the presence of external K+. It is explained in terms of a model in which the conduction pore contains Ba2+, K+, and tetraethylammonium simultaneously, with the K+ binding site located internal to the tetraethylammonium site. Altogether, these results and the known potassium channel structure (Doyle, D.A., J.M. Cabral, R.A. Pfuetzner, A. Kuo, J.M. Gulbis, S.L. Cohen, B.T. Chait, and R. MacKinnon. 1998. Science. 280:69–77) imply that the lock-in site and the Ba2+ sites are the external and internal ion sites of the selectivity filter, respectively

Conformal Invariance of the Pure Spinor Superstring in a Curved Background

It is shown that the pure spinor formulation of the heterotic superstring in a generic gravitational and super Yang-Mills background has vanishing one-loop beta functions.Comment: Reference adde

The influence of Tellurium an Folic Acid Adminitration on Coping Behavioural Parameters in Maturing Rats: Transgenerational effects

A previous study of our laboratory have shown that Tellurium (Te), a metalloid with low concentrations in soil and water in the earth, is able to modify important behavioural parameters related to cognitive functions when administered orally in maturing rats. Exposition of chronic non-toxic doses of Te affected spontaneous lateralized exploration, social interaction behaviour, and survival responses in the treated rats. Te effects were blocked by the simultaneous administration of folic acid, a well-known methyl group donor in the cell, suggesting an epigenetic mode of action of Te. Te behavioural effects on the second generation (F1 ) still were found in the next third generation (F2 ). In order to evaluate if these transgenerational behavioural alterations in F2 were depending on DNA methylating mechanisms, as observed in the F1 generation, F1 rats were mated at 90 days of age. Two groups of animals in the F2 offspring were formed; one treated with and the other not treated with folic acid. Results showed that the untreated folic acid F2 maturing rats, conserved the same pattern of behavioural alterations than its parents (F1 ), in spite that they were not exposed to Te. Those F2 animals treated with folic acid, instead recovered the normal behavioural responses in the three tests performed to evaluate coping behaviour. Results suggest that the molecular mechanism of Te is dependent on DNA methylating reactions, which is one of the molecular processes of epigenetic modulation in mammalsFil: Ratti, Silvia Gabriela. Universidad Nacional de Cuyo; ArgentinaFil: Sacchi, Osvaldo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Alvarez, Edgardo O. Universidad Nacional de Cuyo; Argentin

The inorganic chemicals that surround us: role of tellurium, selenium and zinc on behavioural functions in mammals

Living organisms live in continuous interaction with its environment.During this process changes in one can induce adaptive responses on theother. Many factors in the environment have been studied with thenotorious distinction of been rare or to be of high intensity strength in itsinteraction with living organisms. However, little attention has been puton some factors that have constant interaction with organisms butusually have low intensity strength, such as the case of the inorganicchemical environment that surrounds us. In this review, the interactionbetween the chemical element and living organisms is discussed under atheoretical model of interaction between compartments, giving attentionto tellurium (Te), zinc (Zn) and selenium (Se) on some cognitivefunctions in human and animals. After studies in our laboratory of thephenotypic expression of the HSR (Hand Skill Relative) gene in schoolchildren community living in geographic zone rich in minerals andmines of La Rioja province, Argentine, where Te was found to be inhigher non‐toxic concentrations, a translational experimental model tomaturing rats exposed to this trace element was made. Te was found toincrease some parameters related to locomotion in an open field inducedby novelty and exploratory motivation. At the same time, inhibition oflateralized responses, survival responses and social activity was alsoobserved. Some of these changes, particularly those related tolateralization had similarity with that found previously in children of LaRioja province. Discussion of similarities and discrepancies of biologiceffects between animals and humans, about the possible meaning of Teand its interaction with Zn and Se with relevance to humans wasanalyzed.Fil: Alvarez, Edgardo Oscar. Universidad Catolica de Cuyo. Sede San Luis. Facultad de Ciencias Medicas. Laboratorio de Epigenesis y Neuropsicofarmacologia Experimental; ArgentinaFil: Sacchi, Osvaldo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Catolica de Cuyo. Sede San Luis. Facultad de Ciencias Medicas. Laboratorio de Epigenesis y Neuropsicofarmacologia Experimental; ArgentinaFil: Ratti, Silvia Gabriela. Universidad Catolica de Cuyo. Sede San Luis. Facultad de Ciencias Medicas. Laboratorio de Epigenesis y Neuropsicofarmacologia Experimental; Argentin

Behavioural multigenerational effect induced by the administration of very low doses of zinc during pregnancy, lactation and prepuberal period in the rat

In previous studies from this laboratory, the chronic administration of ZnTe during pregnancy, lactation and prepuberal stages of litters (F1 generation), the behavioural patterns of motivated exploration, lateralized exploration, social activity and survival responses of the maturing rats were modified. In order to find out if these affected behaviours should extend to the next generation, F1 litter rats, exposed previously to tellurium (Te) up to 30 days of age were left at rest with no further treatment up to reach 70 day-old. Then, F1 female rats were mated with normal untreated male rats, and in the next generation (F2), the litter rats at 30 day-old preserved the modified behaviours previously observed in their parents. This evidence suggested that Te effects were intergenerational. In the present work, considering that in the first study ZnTe was used, and it is well known that Zn ion has many physiological functions in the cell, experiments were done in order to define if Zn could have a similar intergenerational effect than Te. Working with the same experimental setup than in previous experiments, but using ZnCl2 instead of ZnTe, results shown that none of the behavioural responses studied were affected in F1 generation. However, in F2 generation lateralized exploration and survival behaviour were inhibited, suggesting that Zn also has an intergenerational effect.Fil: Ratti, Silvia Gabriela. Universidad Catolica de Cuyo. Sede San Luis. Facultad de Ciencias Medicas. Laboratorio de Epigenesis y Neuropsicofarmacologia Experimental; ArgentinaFil: Sacchi, Osvaldo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Alvarez, Edgardo Oscar. Universidad Catolica de Cuyo. Sede San Luis. Facultad de Ciencias Medicas. Laboratorio de Epigenesis y Neuropsicofarmacologia Experimental; Argentin

Efectos derrame interestatales y transfronterizos de la red de carreteras: Un estudio para México

El objetivo de esta investigación es identificar la existencia de efectos derrame de la infraestructura carretera nacional y transfronteriza de Estados Unidos sobre la producción en México, a través de la implementación de un modelo de fronteras estocásticas. Para ello, se han elaborado indicadores espaciales que capturan estos efectos y que recogen la influencia de las entidades federativas contiguas a cada una de ellas. Los resultados muestran que tanto las carreteras nacionales como las transfronterizas generan un efecto favorable para la producción, reduciendo la ineficiencia técnica estatal, generando efectos derrame entre las entidades federativas contiguas

Eficiencia técnica de las entidades federativas de México

El interés por tener una medida de la eficiencia técnica parte de que se acepta la existencia de una brecha entre el supuesto teórico de eficiencia técnica total y la observada en la realidad empírica, por lo que se abre la posibilidad de mejorar el output únicamente optimizando los inputs. En este contexto, el objetivo de esta investigación es obtener un indicador de niveles de eficiencia técnica que permita identificar la posición relativa y la evolución temporal en las entidades federativas de México respecto a su frontera eficiente. En particular, se aproxima la frontera de producción mediante el análisis de fronteras estocásticas planteado por Battese y Coelli. El resultado general permite identificar que se puede ampliar la producción en aproximadamente 20%. Asimismo, se elabora un ranking de eficiencia técnica para las entidades federativas de México

Modulation of the Shaker K+Channel Gating Kinetics by the S3–S4 Linker

In Shaker K+ channels depolarization displaces outwardly the positively charged residues of the S4 segment. The amount of this displacement is unknown, but large movements of the S4 segment should be constrained by the length and flexibility of the S3–S4 linker. To investigate the role of the S3–S4 linker in the ShakerH4Δ(6–46) (ShakerΔ) K+ channel activation, we constructed S3–S4 linker deletion mutants. Using macropatches of Xenopus oocytes, we tested three constructs: a deletion mutant with no linker (0 aa linker), a mutant containing a linker 5 amino acids in length, and a 10 amino acid linker mutant. Each of the three mutants tested yielded robust K+ currents. The half-activation voltage was shifted to the right along the voltage axis, and the shift was +45 mV in the case of the 0 aa linker channel. In the 0 aa linker, mutant deactivation kinetics were sixfold slower than in ShakerΔ. The apparent number of gating charges was 12.6 ± 0.6 eo in ShakerΔ, 12.7 ± 0.5 in 10 aa linker, and 12.3 ± 0.9 in 5 aa linker channels, but it was only 5.6 ± 0.3 eo in the 0 aa linker mutant channel. The maximum probability of opening (Pomax) as measured using noise analysis was not altered by the linker deletions. Activation kinetics were most affected by linker deletions; at 0 mV, the 5 and 0 aa linker channels' activation time constants were 89× and 45× slower than that of the ShakerΔ K+ channel, respectively. The initial lag of ionic currents when the prepulse was varied from −130 to −60 mV was 0.5, 14, and 2 ms for the 10, 5, and 0 aa linker mutant channels, respectively. These results suggest that: (a) the S4 segment moves only a short distance during activation since an S3–S4 linker consisting of only 5 amino acid residues allows for the total charge displacement to occur, and (b) the length of the S3–S4 linker plays an important role in setting ShakerΔ channel activation and deactivation kinetics

Macroalgae ecosystem engineering effects mediated by an invasive reef-builder polychaete in a Southwestern Atlantic coastal lagoon

Macroalgae in Mar Chiquita coastal lagoon (37◦ 40′ S, 57◦ 23′ W, Argentina) settle on small-hard substrates on sediments and complex reef-like structures with tubes and crevices of the invader polychaete Ficopomatus enigmaticus (Fauvel, 1923) acting as ecosystem engineers with multiple community structuring effects. In this study, we compared the structural effects of macroalgae generating new habitat for other organisms in two systems with originally different structural complexity. Therefore, we hypothesized that macroalgae relative importance as an ecosystem engineer providing new habitat and refuge for other organisms would be higher in flat soft-sediments than on reefs. Through sampling and experimental studies, results showed that macrofaunal assemblages were different between areas with and without macroalgae in both reefs and sediment. Experimental results on macroalgae and macroalgae-mimics to separate structural effects in both reefs and sediment showed that macroalgae affect macrofauna on both systems but, structural mechanisms did not prevail in the reefs or sediment. The effect varied on species responses and physical gradients (i.e., depth) of each type of area. Therefore, our results did not support our hypothesis and suggest that macroalgae effects are the result of a summary of their multiple effects in interaction with species and habitat type.Fil: Bazterrica, Maria Cielo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Alvarez, María Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; ArgentinaFil: Iribarne, Oscar Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Botto, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; Argentin

SPARC Controls Melanoma Cell Plasticity through Rac1.

Cell transition to a more aggressive mesenchymal-like phenotype is a hallmark of cancer progression that involves different steps and requires tightly regulated cell plasticity. SPARC (Secreted Protein Acidic and Rich in Cysteine) is a matricellular protein that promotes this transition in various malignant cell types, including melanoma cells. We found that suppression of SPARC expression in human melanoma cells compromised cell migration, adhesion, cytoskeleton structure, and cell size. These changes involved the Akt/mTOR pathway. Re-expression of SPARC or protein addition restored all the cell features. Suppression of SPARC expression was associated with increased Rac1-GTP levels and its membrane localization. Expression of the dominant negative mutant of Rac1 counteracted almost all the changes observed in SPARC-deficient cells. Overall, these data suggest that most of the SPARC-mediated effects occurred mainly through the blockade of Rac1 activity.Fil: Salvatierra Colussi, Edgardo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Alvarez, Mariano J.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Leishman, Claudia C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Rivas Baquero, Elvia Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Lutzky, Viviana P.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina. The Royal Brisbane Hospital; AustraliaFil: Chuluyan, Hector Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin