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The kinetics of the nopol synthesis by Prins condensation of β-pinene and paraformaldehyde over Sn-MCM-41 synthesized by impregnation was evaluated using the initial reaction rate method. The reaction rate equation obtained from a kinetic model based on the Langmuir–Hinshelwood formalism with the surface reaction of adsorbed reactants on catalytic sites of the same nature as the limiting step, gave a good prediction of the experimental data. The effect of temperature on the kinetics of nopol synthesis over Sn-MCM-41 obtained by impregnation was studied between 75 and 100 °C. The robustness analysis of the kinetic model showed that the surface reaction constant, k sr ′ , should be about 0.185 mol g−1 h−1 at 90 °C, while the ratio between the adsorption equilibrium constant of β-pinene, KA, and formaldehyde species, KB, is approximately 1.2:1 (KA:KB). The obtained apparent activation energy and pre-exponential factor are 78 kJ/mol and 2.3 × 1010 mol g−1 h−1, respectively, but compensation effect analysis using both experimental and simulated data gave strong evidence of the dependency in temperature of the apparent Arrhenius parameters.

Maternal infections with gram-negative bacteria are associated with miscarriage and are one of the most common complications during pregnancy. Previous studies from our group have shown that lipopolysaccharide (LPS)-activated infiltrating peripheral blood mononuclear cells (PBMC) into decidual tissue plays an important role in the establishment of a local inflammatory process that results in embryo cytotoxicity and early embryo resorption. Moreover, we have also shown that an increased endocannabinoid tone mediates LPS-induced deleterious effects during early pregnancy loss. Here, we sought to investigate whether the infiltrating PBMC modulates the decidual endocannabinoid tone and the molecular mechanisms involved. PBMC isolated from 7-day pregnant mice subjected to different treatments were co-cultured in a transwell system with decidual tissue from control 7-day pregnant mice. Decidual fatty acid amide hydrolase (FAAH) activity was measured by radioconvertion, total decidual protein nitration by Western blot (WB), and decidual FAAH nitration by immunoprecipitation followed by WB. We found that co-culture of PBMC obtained from LPS-treated mice increased the level of nitration of decidual FAAH, which resulted in a negative modulation of decidual FAAH activity. Interestingly, co-treatment with progesterone or aminoguanidine prevented this effect. We found that LPS-treated PBMC release high amounts of nitric oxide (NO) which causes tyrosine nitration of decidual FAAH, diminishing its enzymatic activity. Inactivation of FAAH, the main degrading enzyme of anandamide and similar endocannabinoids, could lead to an increased decidual endocannabinoid tone with embryotoxic effects. J. Cell. Physiol. 232: 1441-1447, 2017. © 2016 Wiley Periodicals, Inc.

O artigo retrata o resultado da meta-avaliação do Relatório de Avaliação de Acessibilidade da Plataforma Lattes do CNPq sob a perspectiva de deficientes visuais. A meta-avaliação foi desenvolvida como instrumento de qualificação da avaliação realizada, partindo das categorias existentes na publicação do Joint Committee on Standards for Educational Evaluation. A metodologia adotada consistiu na utilização de uma lista de verificação com o propósito de julgar o nível de atendimento do objeto avaliado quanto aos padrões da Categoria de Utilidade, definidos pelo Joint Committee. O relatório enfatiza a importância da acessibilidade na web e apresenta resultados relevantes em relação à acessibilidade da Plataforma Lattes no atendimento a pessoas com deficiência visual parcial e total. A meta-avaliação aplicada possibilitou julgar os resultados apresentados no relatório tendo como base as diretrizes do Web Content Accessibility Guidelines 1.0, apontando recomendações e sugestões em acessibilidade na web.

Miscarriage caused by Gram-negative bacteria infecting the female genital tract is one of the most common complications of human pregnancy. Intraperitoneal administration of LPS to 7-days pregnant mice induces embryo resorption after 24 h. Here, we show that LPS induced apoptosis on uterine explants from 7-days pregnant mice and that CB1 receptor was involved in this effect. On the other hand, heparin has been widely used for the prevention of pregnancy loss in women with frequent miscarriage with or without thrombophilia. Besides its anticoagulant properties, heparin exerts anti-inflammatory, immunomodulatory and anti-apoptotic effects. Here, we sought to investigate whether the administration of heparin prevented LPS-induced apoptosis in uterine explants from 7-days pregnant mice. We found that heparin enhanced cell survival in LPS-treated uterine explants and that this effect was mediated by increasing uterine FAAH activity. Taken together, our results point towards a novel mechanism involved in the protective effects of heparin.

Hypoxia-inducible factors (HIFs) are heterodimeric transcription factors central to hypoxia response and cancer development. Within the HIF-2 complex, one domain (HIF-2α PAS-B) contains a large (290 A3) buried cavity filled with water molecules within its hydrophobic core. Such cavities are uncommon except in the case of ligand-binding proteins, leading to the hypothesis that HIF-2α can be regulated by small molecules. The development of artificial HIF-2α inhibitors validates this hypothesis but raises questions about the impact of this cavity on HIF-2α PAS-B structure and function. To answer these points, we used computational methods to construct a repacked protein containing a smaller cavity within the native fold. Experimental validation of a five-mutation variant confirms achieving these objectives and stabilizing the folded structure. Complementary functional data establish that ligands cannot bind this variant although heterodimerization remains unchanged. Altogether, our strategy innovatively addresses the roles of solvated cavities in maintaining protein stability and function.

Companies involved in water and forest resource extraction in Colombia are obliged to compensate for any resulting impacts stemming from their activities, as agreed with the environmental authorities. Compensation usually relates to reforestation or the development of public service infrastructure. However, these initiatives should be more relevant to the local community and ensure that the protection of biodiversity is efficiently undertaken and optimized to support the greatest number of benefits to fauna and flora and the provision of ecosystem services. This paper shows how a partnership between Mansarovar Energy Colombia Ltd., a heavy oil extraction company, and the national and local environmental authorities, resulted in the establishment of buffer zones to support the conservation of the Regional Natural Park "Serranía de las Quinchas". In total one thousand hectares were added to the already existing 21,000 ha that legally constitute the park. This synergy led to a greater impact within the local community, compared to when each entity worked separately.

The endocannabinoid anandamide (AEA) is released by macrophages and microglia on pathological neuroinflammatory conditions such as multiple sclerosis (MS). CD200 is a membrane glycoprotein expressed in neurons that suppresses immune activity via its receptor (CD200R) mainly located in macrophages/microglia. CD200-CD200R interactions contribute to the brain immune privileged status. In this study, we show that AEA protects neurons from microglia-induced neurotoxicity via CD200-CD200R interaction. AEA increases the expression of CD200R1 in LPS/IFN-γ activated microglia through the activation of CB 2 receptors. The neuroprotective effect of AEA disappears when microglial cells derive from CD200R1 -/- mice. We also show that engagement of CD200R1 by CD200Fc decreased the production of the proinflammatory cytokines IL-1β and IL-6, but increased IL-10 in activated microglia. In the chronic phases of Theiler's virus-induced demyelinating disease (TMEV-IDD) the expression of CD200 and CD200R1 was reduced in the spinal cord. AEA-treated animals up-regulated the expression of CD200 and CD200R1, restoring levels found in sham animals together with increased expression of IL-10 and reduced expression of IL-1β and IL-6. Treated animals also improved their motor behavior. Because AEA up-regulated the expression of CD200R1 in microglia, but failed to enhance CD200 in neurons we suggest that AEA-induced up-regulation of CD200 in TMEV-IDD is likely due to IL-10 as this cytokine increases CD200 in neurons. Our findings provide a new mechanism of action of AEA to limit immune response in the inflamed brain. © 2012 Wiley Periodicals, Inc., M. Hernangómez is a predoctoral fellow from the Spanish Ministerio de Ciencia e Innovación.

Theiler's virus (TMEV) infection of the central nervous system (CNS) induces an immune-mediated demyelinating disease in susceptible mouse strains and serves as a relevant infection model for human multiple sclerosis (MS). The endocannabinoid system represents a novel therapeutic target for autoimmune and chronic inflammatory diseases due to its anti-inflammatory properties by regulating cytokine network. IL-12p70 and IL-23 are functionally related heterodimeric cytokines that play a crucial role in the pathogenesis of MS. In the present study we showed that the endocannabinoid anandamide (AEA) downregulated the gene expression of IL-12p70 and IL-23 forming subunits mRNAs in the spinal cord of TMEV-infected mice and ameliorated motor disturbances. This was accompanied by significant decreases on the serological levels of IL-12p70/IL-23 and more interestingly, of IL-17A. In contrast, serum levels of IL-10 resulted elevated. In addition, we studied the signalling pathways involved in the regulation of IL-12p70/IL-23 and IL-10 expression in TMEV-infected microglia and addressed the possible interactions of AEA with these pathways. AEA acted through the ERK1/2 and JNK pathways to downregulate IL-12p70 and IL-23 while upregulating IL-10. These effects were partially mediated by CB2 receptor activation. We also described an autocrine circuit of cross-talk between IL-12p70/IL-23 and IL-10, since endogenously produced IL-10 negatively regulates IL-12p70 and IL-23 cytokines in TMEV-infected microglia. This suggests that by altering the cytokine network, AEA could indirectly modify the type of immune responses within the CNS. Accordingly, pharmacological modulation of endocannabinoids might be a useful tool for treating neuroinflammatory diseases. © 2011 Elsevier Inc., This work was supported by grants from the Spanish Ministerio de Educación y Ciencia [SAF 2007/60038]; the Comunidad Autónoma de Madrid (CAM) [S/SAL0261/2006] and Red Española de Esclerosis Multiple (RD07/0060; REEM; RETICS; ISCIII). F Correa is a CAM FPI Fellow.

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The performances of two gas-channel designs of bipolar plates were investigated by numerical simulations and experimental in-cell tests. The experimental study examined the performances of two gas-channel geometries and materials under cathode and anode flooding conditions. Design 1 consisted in straight-parallel channels with graphite monopolar plates. On the other hand, Design 2 was made of a double-channel serpentine flow field pattern with stainless steel monopolar plates. Design 1 did not provide a uniform flow distribution over the gas diffusion layer, so liquid water was accumulated in certain regions. The flow velocity in Design 2 was higher and produced more uniform electrical current distributions than the straight-parallel channels design. This design, using 304 SS plates, diminished the effect of the electrical resistance related to the mass transfer rate.

Uruguay comparte una extensa frontera con Brasil. En esta zona, los habitantes de ambas márgenes realizan sus compras en aquel país que coyunturalmente resultan más convenientes. Las fuertes alteraciones que ha sufrido el tipo de cambio real bilateral han determinado que la demanda se haya trasladado a un lado y otro de la frontera de forma alternada, repercutiendo en el nivel de empleo generado en dos departamentos fronterizos de Uruguay. En este artículo se presenta un modelo teórico que intenta recoger los principales elementos del fenómeno analizado. Las estimaciones econométricas realizadas validan el modelo planteado y muestran que los mercados laborales de ambos lados de la frontera no están lo suficientemente integrados como para amortiguar los impactos derivados de las variaciones de la demanda.

The effects of microglia-conditioned medium (MCM) on the inducible Nrf2 system in astrocyte-rich cultures were investigated by determination of glutathione (GSH) levels, γglutamylcysteine ligase (γGCL) activity, the protein levels of Nrf2, Keap1, the modulatory subunit of γGCL (γGCL-M) and activated MAP kinases (ERK1/2, JNK and p38). Microglia were either cultured for 24 h in serum-free culture medium to achieve microglia-conditioned medium from non-activated cells (MCM(0) ), used as control condition, or activated with different concentrations (0.1-1,000 ng mL(-1) ) of lipopolysaccharide (LPS) to produce MCM(0.1-1,000) . Acute exposure (24 h) to MCM(100) increased GSH, γGCL activity, the protein levels of γGCL-M, Nrf2, and activated JNK and ERK1/2 in astrocyte-rich cultures. In contrast, treatment with MCM(10) for 24 h decreased components of the Nrf2 system in parallel with activation of p38 MAPK. Stimulation of the Nrf2 system by tBHQ was partly intact after 24 h but blocked after 72 h treatment with MCM(10) and MCM(100) . This down-regulation after 72 h correlated with activation of p38 MAPK and lack of ERK1/2 and JNK activation. The negative effects were partly reversed by an inhibitor of p38 which restored tBHQ mediated protection against oxidative stress. In conclusion, the study showed a negative effect of MCM(10) on the inducible anti-oxidant defense in astrocyte-rich cultures at both 24 and 72 h that correlated with activation of p38 and was partly reversed by a p38 inhibitor. A transient protective effect of MCM(100) on astrocyte-rich cultures against H(2)O(2) toxicity was observed at 24 h which coincided with activation of JNK and ERK1/2.

In this polyphonic pedagogical essay, six members of the Department of English at the University of Puerto Rico at Mayagüez discuss their incorporation of auto/biographical acts into course syllabi for the purpose of facilitating social justice in and through education. Drawing from disciplinarily diverse faculty members holding different contractual positions within the university, this essay demonstrates the widespread need for creating space for student voices as means of supporting agency on- and off-campus, especially in times of disaster, tragedy, and crisis.

The corrosion resistance of several metallic materials was evaluated in the chemical environment encountered in PEM fuel cells. The value of PREN (Pitting Resistance Equivalent Number) was calculated for metallic materials and compared whit the corrosion current. PREN is not useful in bipolar plates research. Merely SS 316 and Inconel 625 are suitable for use as a flow-field plate on the cathodic side of a PEM fuel cell. Inconel 625 has a higher CR, because of its Mo content. The corrosion resistance of AISI 444 is acceptable as material for bipolar plate materials. The corrosion resistance of SS 7222 is higher and cannot been considered as material for bipolar plate materials.

The aim of this study was to evaluate how endocannabinoids interact with excitotoxic processes both in vitro, using primary neural cell cultures, and in vivo, in the TMEV-IDD model of multiple sclerosis. First, we observed that neuronal cells respond to excitotoxic challenges by the production of endocannabinoid molecules which in turn exerted neuroprotective effects against excitotoxicity. The inhibitor of endocannabinoid uptake, UCM707, protected specifically against AMPA-induced excitotoxicity, by activating CB1 and CB2 cannabinoid receptors, as well as the nuclear factor, PPARγ. This neuroprotective effect was reverted by blocking the glial glutamate transporter, GLT-1. Mice subjected to the model of multiple sclerosis showed a decrease in the expression of GLT-1. UCM707 reversed this loss of GLT-1 and induced a therapeutic effect. Our data indicate that the enhancement of the endocannabinoid tone leads to neuroprotection against AMPA-induced excitotoxicity and provides therapeutic effects in this model of multiple sclerosis. © 2009 Elsevier Inc. All rights reserved.

The endocannabinoid system exhibits anti-inflammatory properties by regulating cytokine production. Anandamide (AEA) down-regulates proinflammatory cytokines in a viral model of multiple sclerosis (MS). However, little is known about the mechanisms by which AEA exerts these effects. Microglial cells are the main source of cytokines within the brain and the first barrier of defense against pathogens by acting as antigen presenting cells. IL-10 is a key physiological negative regulator of microglial activation. In this study we show that AEA enhances LPS/IFNgamma-induced IL-10 production in microglia by targeting CB(2) receptors through the activation of ERK1/2 and JNK MAPKs. AEA also inhibits NF-kappaB activation by interfering with the phosphorylation of IkappaBalpha, which may result in an increase of IL-10 production. Moreover, endogenously produced IL-10 negatively regulates IL-12 and IL-23 cytokines, which in its turn modify the pattern of expression of transcription factors involved in Th commitment of splenocytes. This suggests that by altering the cytokine network, AEA could indirectly modify the type of immune responses within the central nervous system (CNS). Accordingly, pharmacological modulation of AEA uptake and degradation might be a useful tool for treating neuroinflammatory diseases.

Stainless steel Type 444 is an excellent material for use in the manufacture of bipolar plates. It is comparable to austenitic stainless steel Type 316 in its corrosion resistance but has the advantage of being half less expensive. The coatings that had the best performance were chromium carbide and gold. Corrosion resistance of ferritic stainless steels 439 and 441, with a Ni-Cr and NiCrAlY coatings, were evaluated under simulated cathodic PEMFC environment. The corrosion current density of the coatings is higher than the US Department of Energy target value and they are not a feasible option to be used in bipolar plates for fuel cell applications. A possible explanation of the inadequate corrosion resistance is the segregation of the elements. The XRD and SEM measurements indicate that the corrosion mechanisms are different for NiCr and NiCrAlY. We have concluded that it is technically possible to produce bipolar plates in Mexico.

Cannabinoids have recently been approved as a treatment for pain in multiple sclerosis (MS). Increasing evidence from animal studies suggests that this class of compounds could also prove efficient to fight neurodegeneration, demyelination, inflammation and autoimmune processes occurring in this pathology. However, the use of cannabinoids is limited by their psychoactive effects. In this context, potentiation of the endogenous cannabinoid signalling could represent a substitute to the use of exogenously administrated cannabinoid ligands. Here, we studied the expression of different elements of the endocannabinoid system in a chronic model of MS in mice. We first studied the expression of the two cannabinoid receptors, CB1 and CB2, as well as the putative intracellular cannabinoid receptor peroxisome proliferator-activated receptor-α. We observed an upregulation of CB 2, correlated to the production of proinflammatory cytokines, at 60 days after the onset of the MS model. At this time, the levels of the endocannabinoid, 2-arachidonoylglycerol, and of the anti-inflammatory anandamide congener, palmithoylethanolamide, were enhanced, without changes in the levels of anandamide. These changes were not due to differences in the expression of the degradation enzymes, fatty acid amide hydrolase and monoacylglycerol lipase, or of biosynthetic enzymes, diacylglycerol lipase-α and N-acylphosphatidylethanolamine phospholipase-D at this time (60 days). Finally, the exogenous administration of palmitoylethanolamide resulted in a reduction of motor disability in the animals subjected to this model of MS, accompanied by an anti-inflammatory effect. This study overall highlights the potential therapeutic effects of endocannabinoids in MS. © The Authors (2008)., This work was supported by grants from the MEC (Ministerio de Educación y Ciencia) (SAF‐2006/60038) and the CAM (S‐SAL 2006/0261). F.C. receives a fellowship from the Comunidad Autónoma de Madrid. F.L. was supported by a fellowship from CONACyT, Mexico. The authors are grateful to Epitech, Italy, for support (to S.P. and V.D.M.).

Background: Cannabinoids have been shown to exert beneficial actions in different animal models of multiple sclerosis (MS). However, the use of cannabinoids compounds in human therapy is greatly limited by their psychoactivity. Thus, new hopes in MS therapy have arisen from the evidence for a cannabinoid receptor, termed CB2, which is devoid of psychoactive effects in animal models. Objective: This review discusses the different mechanisms by which CB2 activation could induce therapeutic actions in MS. Methods: Particular focus is given to the potential effects on inflammation/autoimmunity, remyelination and neuroprotection. Conclusion: This review discusses the importance of glial cells in sustaining these effects, as well as the putative secondary effects that would limit the use of CB2 agonists in the treatment of MS. © 2008 Informa UK Ltd.

The endocannabinoid system (eCS), is a complex system, comprising the main endogenous ligands anandamide and 2-arachidonoyl glycerol, the cannabinoid receptors CB1 and CB2 and the biosynthetic and degrading enzymes. Cumulative evidence shows that the eCS plays an important role in reproduction, from egg fertilization to parturition. Therefore, alterations in this system, either by recreation/therapeutic use of cannabis or deregulation of the endogenous cannabinoids, might lead to adverse pregnancy outcomes, including retardation in embryo development, poor blastocyst implantation, inhibition of decidualization, miscarriage and compromised placentation. Nevertheless, the molecular mechanisms by which the eCS participates in different stages of pregnancy remain poorly understood. In this review, we will examine the evidence from animal and human studies to support the role of the eCS in implantation, early-to-late pregnancy and placentation as well as the difficulties of targeting this system for treatment of female infertility. Fil: Correa, Fernando Gabriel. 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 Fil: Wolfson, Manuel Luis. 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 Fil: Valchi, Paula. 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 Fil: Aisemberg, Julieta. 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 Fil: Franchi, Ana Maria. 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

Appropriate systemic progesterone levels are critical for a successful pregnancy outcome. Precocious loss of luteal progesterone secretion leads to miscarriage in rodents. We have previously shown that lipopolysaccharide (LPS) administration to pregnant mice induces embryonic resorption accompanied by a dramatic decrease in systemic progesterone levels in a murine model of inflammatory miscarriage. Furthermore, we showed that the endocannabinoid system (eCS) mediated LPS deleterious effects. The aim of this study was to explore the participation of the endocrine system in the LPS-induced miscarriage as well as the role of the eCS in this process. We found that LPS increased the expression of COX-2 and the production of PGF2α in the uterus of 7-days pregnant mice. Increased production of PGF2α resulted in a lower expression of prolactin receptor in the ovary and a marked regression of corpora lutea (CL), which thus produces less progesterone and consequently, results in embryo resorption. Remarkably, these effects were completely absent in CB1-knockout pregnant mice. Our results clearly suggest that the absence of CB1 receptor confers resistance to LPS deleterious actions during pregnancy. Moreover, lack of CB1 receptor protected from LPS-induced premature luteal regression. Fil: Schander, Julieta Aylen. 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 Fil: Correa, Fernando Gabriel. 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 Fil: Bariani, Maria Victoria. 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 Fil: Blanco, Julieta. 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 Fil: Cymeryng, Cora Betriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Jensen, Cristian Federico. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Wolfson, Manuel Luis. 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 Fil: Franchi, Ana Maria. 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

Excessive ethanol drinking has deleterious effects on the brain. However, the effects of alcohol on microglia, the main mediator of the brain´s innate immune response remain poorly understood. On the other hand, the endocannabinoid system plays a fundamental role in regulating microglial reactivity and function. Here we studied the effects of acute ethanol exposure to murine BV2 microglial cells on N-acyl phosphatidylethanolamine-phospholipase D (NAPE-PLD), a major synthesizing enzyme of anandamide and other N-acylethanolamines. We found that ethanol downregulated microglial NAPE-PLD expression by activating cAMP/PKA and ERK1/2. These signaling pathways converged on increased phosphorylation of CREB. Moreover, ethanol induced an increase in histone acetyltransferase activity which led to higher levels of acetylation of histone H3. Taken together, our results suggest that ethanol actions on microglial NAPE-PLD expression might involve epigenetic mechanisms. Fil: Correa, Fernando Gabriel. 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 Fil: de Laurentiis, Andrea. 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 Fil: Franchi, Ana Maria. 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

Tropomyosin (Tm) is a dimeric coiled-coil protein, composed of 284 amino acids (410Å), that forms linear homopolymers through head-to-tail interactions at low ionic strength. The head-to-tail complex involves the overlap of approximately nine N-terminal residues of one molecule with nine C-terminal residues of another Tm molecule. In this study, we investigate the influence of 2,2,2-trifluoroethanol (TFE) and glycerol on the stability of recombinant Tm fragments (ASTm1–142, Tm143–284(5OHW269)) and of the dimeric head-to-tail complex formed by the association of these two fragments. The C-terminal fragment (Tm143–284(5OHW269)) contains a 5-hydroxytryptophan (5OHW) probe at position 269 whose fluorescence is sensitive to the head-to-tail interaction and allows us to accompany titrations of Tm143–284(5OHW269) with ASTm1–142 to calculate the dissociation constant (Kd) and the interaction energy at TFE and glycerol concentrations between 0% and 15%. We observe that TFE, but not glycerol, reduces the stability of the head-to-tail complex. Thermal denaturation experiments also showed that the head-to-tail complex increases the overall conformational stability of the Tm fragments. Urea and thermal denaturation assays demonstrated that both TFE and glycerol increase the stability of the isolated N- and C-terminal fragments; however, only TFE caused a significant reduction in the cooperativity of unfolding these fragments. Our results show that these two cosolvents stabilize the structures of individual Tm fragments in different manners and that these differences may be related to their opposing effects on head-to-tail complex formation.

Inflammation, autoimmune response, demyelination and axonal damage are thought to participate in the pathogenesis of multiple sclerosis (MS). Understanding whether axonal damage causes or originates from demyelination is a crucial issue. Excitotoxic processes may be responsible for white matter and axonal damage. Experimental and clinical studies indicate that cannabinoids could prove efficient in the treatment of MS. Using a chronic model of MS in mice, we show here that clinical signs and axonal damage in the spinal cord were reduced by the AMPA antagonist, NBQX. Amelioration of symptomatology by the synthetic cannabinoid HU210 was also accompanied by a reduction of axonal damage in this model. Moreover, HU210 reduced AMPA-induced excitotoxicity both in vivo and in vitro through the obligatory activation of both CB1 and CB2 cannabinoid receptors. Together, these data underline the implication of excitotoxic processes in demyelinating pathologies such as MS and the potential therapeutic properties of cannabinoids. © 2006 Elsevier Inc. All rights reserved., FD is an I3P postdoctoral fellow (CSIC, Spain). This work was supported by the CICYT (Grant #002004/416, Ministerio de Educación y Ciencia, Spain).

Genital tract infections caused by Gram-negative bacteria induce miscarriage and are one of the most common complications of human pregnancy. LPS administration to 7-day pregnant mice induces embryo resorption after 24h, with nitric oxide playing a fundamental role in this process. We have previously shown that progesterone exerts protective effects on the embryo by modulating the inflammatory reaction triggered by LPS. Here we sought to investigate whether the in vivo administration of progesterone modulated the LPS-induced nitric oxide production from peripheral blood mononuclear cells from pregnant and non-pregnant mice. We found that progesterone downregulated LPS-induced nitric oxide production by a progesterone receptor-independent mechanism. Moreover, our results suggest a possible participation of glucocorticoid receptors in at least some of the anti-inflammatory effects of progesterone. Fil: Wolfson, Manuel Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Schander, Julieta Aylen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Bariani, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Correa, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Franchi, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina

Genital tract infections are a common complication of human pregnancy that can result in miscarriage. We have previously shown that a lipopolysaccharide (LPS) induces embryonic resorption in a murine model of inflammatory miscarriage. This is accompanied by a dramatic decrease in systemic progesterone levels associated with a robust pro-inflammatory response that results in embryo resorption. Here, we tested the hypothesis that the endogenous cannabinoid system (eCS), through cannabinoid receptor 1 (CB1), plays a role in regulating progesterone levels and, therefore, the pro-inflammatory response. We show that LPS treatment in pregnant mice causes significant changes in the eCS ligands, which are reversed by progesterone treatment. We further show the CB1-KO mice maintain higher plasma progesterone levels after LPS treatment, which is associated with a feebler uterine inflammatory response and a significant drop in embryo resorption. These data suggest that manipulation of CB1 receptors and/or ligands is a potential therapeutic avenue to decrease infection-induced miscarriage. Fil: Wolfson, Manuel Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Correa, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Leishman, Emma. Indiana University; Estados Unidos Fil: Vercelli, Claudia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación En Biomedicina de Buenos Aires; Argentina Fil: Cymeryng, Cora Betriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Blanco, Julieta . Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Bradshaw, Heather B.. Indiana University; Estados Unidos Fil: Franchi, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina

BACKGROUND: Stress affects surgeons both during training and during professional activity. OBJECTIVE: To compare stress levels affecting surgical residents during the simulated initial assessment and management in the Advanced Trauma Life Support practical exam vs initial assessment and management of trauma patients in the emergency room. METHOD: Eighteen surgical residents were evaluated under basal conditions, during the Advanced Trauma Life Support simulation, and during emergency room initial care. Heart rate, systolic arterial pressure, and diastolic arterial pressure were measured. The Student t test was used to test for differences between means, with statistical significance declared when P < .05. RESULTS: Heart rate and systolic arterial pressure were increased at the beginning and at the end of Advanced Trauma Life Support simulation and emergency room initial care. diastolic arterial pressure was only increased at the end of the Advanced Trauma Life Support simulation. Comparing values obtained during the Advanced Trauma Life Support simulation with those obtained during emergency room initial care, heart rate and systolic arterial pressure were significantly higher during the Advanced Trauma Life Support simulation both at the beginning and end of the test events. However, diastolic arterial pressure was only significantly higher for Advanced Trauma Life Support simulation compared emergency room at the end of the procedures. These results suggest that the simulation in the practical exam portion of the Advanced Trauma Life Support course is more stressful for the resident surgeon than is the actual initial assessment and care of trauma patients in an emergency room.OBJETIVO: Comparar os níveis de stress que afetam os residentes de cirurgia durante a avaliação inicial simulada nos cursos Advanced Trauma Life Support versus a avaliação do trauma do paciente na sala de emergência. MÉTODO: Dezoito residentes em cirurgia foram avaliados em condições basais no curso de Advanced Trauma Life Support e na sala de emergência. Foram medidas a freqüência cardíaca, pressões arterial sistólica e diastólica. ESTATÍSTICAS: Teste t do Estudante. Significantemente p

Theiler's virus infection of the central nervous system (CNS) induces an immune-mediated demyelinating disease in susceptible mouse strains and serves as a relevant infection model for human multiple sclerosis (MS). Cannabinoids have been shown to exert beneficial effects on animal models of MS and evidence suggests that the endocannabinoid system plays a role in the tonic control of spasticity. In this study we show that OMDM1 [(R)-N-oleoyl-(1′-hydroxybenzyl)-2′-ethanolamine] and OMDM2 [(S)-N-oleoyl-(1′-hydroxybenzyl)-2′-ethanolamine], two selective inhibitors of the putative endocannabinoid transporter and hence of endocannabinoid inactivation, provide an effective therapy for Theiler murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). Treatment of TMEV-infected mice with OMDM1 and OMDM2 enhanced anandamide levels in the spinal cord and ameliorated motor symptoms. This was associated with a down-regulation of inflammatory responses in the spinal cord. In addition we show that OMDM1 and OMDM2 down-regulate macrophage function by (i) decreasing the surface expression of major histocompatibility complex (MHC) class II molecules, (ii) inhibiting nitric oxide synthase-2 (NOS-2) expression and (iii) reducing the production of the pro-inflammatory cytokines interleukin-1beta (IL-1β) and interleukin-12 (IL-12p40). Taken together, these results point to the manipulation of the endocannabinoid system as a possible strategy to develop future MS therapeutic drugs.

The purpose of this study is to determine the demographic and clinical profile of patients with muscle-skeletal chronic pain and treated at the three levels of health public services. One hundred and fifty patients were evaluated, being divided in three groups according to the clinical setting of origin: Basic Unit of Health (BUH), City Specialty Clinic (CSC) and University Clinic (UC).It was observed a strong female predominance in the three groups.(BUH - 74%; CSC - 66%; UC - 80%). The observed age distribution showed that most of the patients from BUH were above 60 years old (50%) and most patients of the other two units were between 41 and 60 years old. In relation to joint distribution, most part of patients at the BHU presented with involvement of less than 4 joints (60%) and at the UC more than 4 joints (60%). At the CSC, most of the complains were localized at the vertebral spine. Unspecific diagnoses were reported more often at the BUH (40%) than at the CSC (20%) and UC (16%). There were less discontinuation of treatment at the UC in relation to the BUH and CSC. At the BHU 28% of patients reported continuous treatment in comparison to 74% of the CSC and 92% at UC. At worsening of pain, most patients of BHU used self-medication, while at the CSC and UC patients followed medical prescription. It was concluded that the secondary and tertiary levels of health institutions (CSC, UC) are able to treat pain patients with diseases of higher complexity.

Rice breeding has made important contributions to Latin America. More than 400 cultivars were released from 1975 to 2012, which helped to raise total production to >27 million tonnes obtained from 5.7 million hectares (average for 2010-2012). Rice production provides ?US$8.8 billion for thousands of farmers in Latin America and the Caribbean (LAC). The result of higher yields in the irrigated sector was to triple rice production in LAC while area did not grow, thus preserving more fragile environments. Several estimates on genetic gains for grain yield have been carried out in LAC. In temperate irrigated rice, the estimates are around 1.5-2.6% per year. In the tropical irrigated, it is ?1% and in the upland rice the estimate is ?1.4% per year. Different breeding strategies, including pedigree, modified bulk, recurrent selection methods, anther culture, interspecific crosses, composite populations, quantitative trait loci (QTL) introgression, and recombinant inbred lines, accompanied by shuttle breeding schemes, direct seeding, and evaluation/selection in hot spots for main diseases are being used by CIAT and NARES in the region. In this process, methods for screening for diseases and other stresses were established. Networking has been a cornerstone for success and several networks such as INGER, FLAR, and HIAAL were created. Looking forward, as farmers' yields are approaching the genetic yield potential exhibited by current cultivars, as a result of improved agronomic management, a new breakthrough is needed in terms of more productive cultivars. To achieve this goal, a strategy is needed that includes strong pipelines focused on specific environments and markets; better product profiling; integration between discovery, development, and delivery; and new breeding strategies using cuttingedge technologies and new breeding methods to accelerate genetic gains. (Resume d'auteur)

The central nervous system (CNS) innate immune response includes an arsenal of molecules and receptors expressed by professional phagocytes, glial cells and neurons that is involved in host defence and clearance of toxic and dangerous cell debris. However, any uncontrolled innate immune responses within the CNS are widely recognized as playing a major role in the development of autoimmune disorders and neurodegeneration, with multiple sclerosis (MS) Alzheimer's disease (AD) being primary examples. Hence, it is important to identify the key regulatory mechanisms involved in the control of CNS innate immunity and which could be harnessed to explore novel therapeutic avenues. Neuroimmune regulatory proteins (NIReg) such as CD95L, CD200, CD47, sialic acid, complement regulatory proteins (CD55, CD46, fH, C3a), HMGB1, may control the adverse immune responses in health and diseases. In the absence of these regulators, when neurons die by apoptosis, become infected or damaged, microglia and infiltrating immune cells are free to cause injury as well as an adverse inflammatory response in acute and chronic settings. We will herein provide new emphasis on the role of the pair CD200-CD200R in MS and its experimental models: experimental autoimmune encephalomyelitis (EAE) and Theiler’s virus induced demyelinating disease (TMEV-IDD). The interest of the cannabinoid system as inhibitor of inflammation prompt us to introduce our findings about the role of endocannabinoids (eCBs) in promoting CD200-CD200 receptor (CD200R) interaction and the benefits caused in TMEV-IDD. Finally, we also review the current data on CD200-CD200R interaction in AD, as well as, in the aging brain.

Lima, Alessandro Rodrigues, Kumagai, Alice Fumi, Neto, Fernando Correa Campos (2013): Morphological and biological observations on the stick insect Tithonophasma tithonus (Gray, 1835) (Phasmida: Pseudophasmatidae: Pseudophasmatinae). Zootaxa 3700 (4): 588-592, DOI: http://dx.doi.org/10.11646/zootaxa.3700.4.7

Factors determining the variability of air-pulse pressure to determine the thresholds of laryngeal-pharyngeal reflexes, which are related to swallowing and airway protection, were explored. Potential factors affecting the reproducibility of air-pulses were experimentally evaluated and included in a multiple linear regression model. A novel device controlling these factors and minimizing variability was designed. Its reproducibility was assessed by the coefficient of variation (CV) of the pressures and duration of air-pulses, and its validity was assessed by comparing obtained pressures and durations with desired pressures and durations. Differences in the pressures of airpulse categories were assessed by a one-way ANOVA of repeated measures, a Tukey test and a box and whisker plot. The distance and angle between the exit of the tube conducting the pulses and the surface to be impacted, the diameter of the tube, the feeding pressure of the system, and the duration of air-pulses significantly affected the accuracy of air-pulses. The novel device incorporated electronic valves and a telemeter for use during the fiberoptic endoscopic evaluation of swallowing. The differences between the desired and obtained pressures and durations were below 3%. The CV of the air-pulse pressures of the novel device was 0.02. The CV of air-pulse duration was 0.05. The oneway ANOVA, Tukey test and box and whisker plot showed that the outlet pressures of air-pulse categories had statistically significant differences between them without overlap between categories, which helps to obtain an accurate threshold.

Light is an essential environmental cue for diverse organisms. Many prokaryotic blue light photoreceptors use light, oxygen, voltage (LOV) sensory domains to control the activities of diverse output domains, including histidine kinases (HK). Upon activation, these proteins autophosphorylate a histidine residue before subsequently transferring the phosphate to an aspartate residue in the receiver domain of a cognate response regulator (RR). Such phosphorylation activates the output domain of the RR, leading to changes in gene expression, protein-protein interactions, or enzymatic activities. Here, we focus on one such light sensing LOV-HK from the marine bacterium Erythrobacter litoralis HTCC2594 (EL368), seeking to understand how kinase activity and subsequent downstream effects are regulated by light. We found that photoactivation of EL368 led to a significant enhancement in the incorporation of phosphate within the HK domain. Further enzymatic studies showed that the LOV domain affected both the LOV-HK turnover rate (kcat) and Km in a light-dependent manner. Using in vitro phosphotransfer profiling, we identified two target RRs for EL368 and two additional LOV-HKs (EL346 and EL362) encoded within the host genome. The two RRs include a PhyR-type transcriptional regulator (EL_PhyR) and a receiver-only protein (EL_LovR), reminiscent of stress-triggered systems in other bacteria. Taken together, our data provide a biochemical foundation for this light-regulated signaling module of sensors, effectors, and regulators that control bacterial responses to environmental conditions.

Background/Aims: Both excitotoxicity and neuroinflammation are associated with oxidative stress. One transcription factor, nuclear factor E2-related factor 2 (Nrf2), and one transcription cofactor, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), increase the endogenous antioxidant defence and can thus modulate neuronal cell death. Here, we investigated the temporal effects (after 24 and 72 h) of systemic (i.p.) administration of lipopolysaccharide (LPS) on the cerebral Nrf2 and PGC-1α systems. Methods and Results: Seven-day-old rat pups were injected with LPS (0.3 mg/kg). After 24 h, the protein levels of γ-glutamylcysteine ligase modulatory subunit, γ-glutamylcysteine ligase catalytic subunit, Nrf2, PGC-1α and manganese superoxide dismutase (MnSOD) were increased in parallel with decreased levels of Keap1. These effects were correlated with an increased level of phosphorylated Akt and elevated acetylation of histone 4. In contrast, 72 h following LPS, a decrease in the components of the Nrf2 system in parallel with an increase in Keap1 was observed. The down-regulation after 72 h correlated with phosphorylation of p38 mitogen-activated protein kinase, while there were no changes in PGC-1α and MnSOD protein levels or the acetylation/methylation pattern of histones. Conclusion: Systemic LPS in neonatal rats induced time-dependent changes in brain Nrf2 and PGC-1α that correlated well with the protective effect observed after 24 h (pre-conditioning) and the deleterious effects observed after 72 h (sensitizing) of systemic LPS reported earlier. Collectively, the results point towards Nrf2 and PGC-1α as a possible mechanism behind these effects. Fil: Correa, Fernando Gabriel. University of Gothenburg. Institute of Biomedicine; Suecia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Ljunggren, Elin. University of Gothenburg. Institute of Biomedicine; Suecia Fil: Patil, Jaspal. University of Gothenburg. Institute of Biomedicine; Suecia Fil: Wang, Xiaoyang. University of Gothenburg. Institute of Neuroscience and Physiology; Suecia Fil: Hagberg, Henrik. University of Gothenburg. Institute of Neuroscience and Physiology; Suecia Fil: Mallard, Carina. University of Gothenburg. Institute of Neuroscience and Physiology; Suecia Fil: Sandberg, Mats. University of Gothenburg. Institute of Biomedicine; Suecia

Tumor necrosis factor-α (TNFα) is a pleiotropic molecule that can have both protective and detrimental effects in neurodegeneration. Here we have investigated the temporal effects of TNFα on the inducible Nrf2 system in astrocyte-rich cultures by determination of glutathione (GSH) levels, γglutamylcysteine ligase (γGCL) activity, the protein levels of Nrf2, Keap1, the catalytic and modulatory subunit of γGCL (γGCL-C and γGCL-M respectively). Astrocyte-rich cultures were exposed for 24 or 72 h to different concentrations of TNFα. Acute exposure (24 h) of astrocyte-rich cultures to 10 ng/mL of TNFα increased GSH, γGCL activity, the protein levels of γGCL-M, γGCL-C and Nrf2 in parallel with decreased levels of Keap1. Antioxidant responsive element (ARE)-mediated transcription was blocked by inhibitors of ERK1/2, JNK and Akt whereas inactivation of p38 and GSK3β further enhanced transcription. In contrast treatment with TNFα for 72 h decreased components of the Nrf2 system in parallel with an increase of Keap1. Stimulation of the Nrf2 system by tBHQ was intact after 24 h but blocked after 72 h treatment with TNFα. This down-regulation after 72 h correlated with activation of p38 MAPK and GSK3β, since inhibition of these signalling pathways reversed this effect. The upregulation of the Nrf2 system by TNFα (24 h treatment) protected the cells from oxidative stress through elevated γGCL activity whereas the down-regulation (72 h treatment) caused pronounced oxidative toxicity. One of the important implications of the results is that in a situation where Nrf2 is decreased, such as in Alzheimer’s disease, the effect of TNFα is detrimental. Fil: Correa, Fernando Gabriel. University Goteborg; Suecia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Mallard, Carina. University Goteborg; Suecia Fil: Nilsson, Michael. University Goteborg; Suecia Fil: Sandberg, Mats. University Goteborg; Suecia

Straighthead, a physiological disorder characterized by sterile florets and distorted spikelets, causes significant yield losses in rice, and occurs in many countries. The current control method of draining paddies early in the season stresses plants, is costly, and wastes water. Development of resistant cultivar is regarded as the most efficient way for its control. We mapped a QTL for straighthead resistance using two recombinant inbred line (RIL) F(9) populations that were phenotyped over two years using monosodium methanearsonate (MSMA) to induce the symptoms. One population of 170 RILs was genotyped with 136 SSRs and the other population of 91 RILs was genotyped with 159 SSRs. A major QTL qSH-8 was identified in an overlapping region in both populations, and explained 46% of total variation in one and 67% in another population for straighthead resistance. qSH-8 was fine mapped from 1.0 Mbp to 340 kb using 7 SSR markers and further mapped to 290 kb in a population between RM22573 and InDel 27 using 4 InDel markers. SSR AP3858-1 and InDel 11 were within the fine mapped region, and co-segregated with straighthead resistance in both RIL populations, as well as in a collection of diverse global accessions. These results demonstrate that AP3858-1 and InDel 11 can be used for marker-assisted selection (MAS) for straighthead resistant cultivars, which is especially important because there is no effective way to directly evaluate straighthead resistance.

WNK1 [with no lysine (K)-1] is a 250-kDa serine/threonine protein kinase involved in the maintenance of cellular salt levels and is directly linked to a hereditary form of hypertension. Here, we report the solution NMR structure of the autoinhibitory domain of WNK1 (WNK1-AI), a small regulatory subunit that lies immediately C-terminal of the kinase domain. We show that this domain is a homolog of the RFXV-binding PASK/FRAY homology 2 (PF2) domain found in OSR (oxidative stress responsive) and SPAK (serine/threonine proline-alanine-rich) kinases, which are substrates of WNK1. The WNK1-AI has a circularly permuted topology relative to the OSR1-PF2 domain. Nevertheless, like PF2 domains, WNK1-AI binds peptides that contain an RFXV motif with micromolar affinities as assessed by changes in (1)H,(15)N heteronuclear single quantum coherence spectra. Mutations to the WNK1-AI and binding peptides confirm a similar binding mode.

The recently identified plant photoreceptor UVR8 triggers regulatory changes in gene expression in response to ultraviolet-B (UV-B) light via an unknown mechanism. Here, crystallographic and solution structures of the UVR8 homodimer, together with mutagenesis and far-UV circular dichroism spectroscopy, reveal its mechanisms for UV-B perception and signal transduction. β-propeller subunits form a remarkable, tryptophan-dominated, dimer interface stitched together by a complex salt-bridge network. Salt-bridging arginines flank the excitonically coupled cross-dimer tryptophan “pyramid” responsible for UV-B sensing. Photoreception reversibly disrupts salt bridges, triggering dimer dissociation and signal initiation. Mutation of a single tryptophan to phenylalanine re-tunes the photoreceptor to detect UV-C wavelengths. Our analyses establish how UVR8 functions as a photoreceptor without a prosthetic chromophore to promote plant development and survival in sunlight.

RESUMEN: Se comparó la actividad de Sn-MCM-41 y Sn-SBA-15 para la síntesis de nopol a partir de β-pineno y paraformaldehído. Los materiales se prepararon por los métodos hidrotérmico y el de impregnación húmeda incipiente, utilizando cloruro estañoso como sal precursora de Sn. Los catalizadores sintetizados por impregnación presentaron mayor actividad y fueron más selectivos a nopol que los materiales obtenidos por el método hidrotérmico. La conversión de β-pineno obtenida con Sn-MCM-41 fue similar a la obtenida con Sn-SBA-15. Mediante síntesis hidrotérmica, se obtuvo especies de Sn(IV) en forma de agregados de SnO y substituyendo isomórficamente Si en la MCM-41 y la SBA-15, respectivamente. ABSTRACT: The catalytic activity of Sn-MCM-41 and Sn-SBA-15 for nopol synthesis from β-pinene and paraformaldehyde was compared in this work. The materials were prepared by the hydrothermal and the incipient wetness impregnation methods using stannous chloride as Sn precursor. In contrast to hydrothermal methods, impregnation leads to more active and selective materials for nopol production from β-pinene. β-Pinene conversion over Sn-MCM-41 and Sn-SBA-15 was similar. In the materials obtained by hydrothermal procedures, Sn(IV) species were detected as bulk SnO in MCM-41 and 2 isomorphously substituting Si in SBA-15. COL0001941

En el Valle del Cauca, Colombia, se estudió la relación de un barrenador del tallo del arroz, Rupela albinella, con la pudricíón del tallo, Sclerotium oryzae. La larva y las heridas causadas por ella están asociadas a la aparición de la pudrición del tallo, pero la infección fungal no depende de la presencia de larvas. El número de larvas y las heridas causadas por ellas y los tallos con infección aumentaron con la edad de la planta.

Histone deacetylase (HDAC) inhibitors have promising neuroprotective and anti-inflammatory properties although the exact mechanisms are unclear. We have earlier showed that factors from lipopolysaccharide (LPS)-activated microglia can down-regulate the astroglial nuclear factor-erythroid 2-related factor 2 (Nrf2)-inducible anti-oxidant defence. Here we have evaluated whether histone modification and activation of GSK3β are involved in these negative effects of microglia. Microglia were cultured for 24 h in serum-free culture medium to achieve microglia-conditioned medium from non-activated cells (MCM(0)) or activated with 10 ng/mL of LPS to produce MCM(10). Astrocyte-rich cultures treated with MCM(10) showed a time-dependent (0-72 h) increase in astroglial HDAC activity that correlated with lower levels of acetylation of histones H3 and H4 and decreased levels of the transcription factor Nrf2 and γ-glutamyl cysteine ligase modulatory subunit (γGCL-M) protein levels. The HDAC inhibitors valproic acid (VPA) and trichostatin-A (TSA) elevated the histone acetylation levels, restored the Nrf2-inducible anti-oxidant defence and conferred protection from oxidative stress-induced (H(2)O(2)) death in astrocyte-rich cultures exposed to MCM(10). Inhibitors of GSK3β (lithium) and p38 MAPK (SB203580) signaling pathways restored the depressed histone acetylation and Nrf2-related transcription whereas an inhibitor of Akt (Ly294002) caused a further decrease in Nrf2-related transcription. In conclusion, the study shows that well tolerated drugs such as VPA and lithium can restore an inflammatory induced depression in the Nrf2-inducible antioxidant defence, possibly via normalised histone acetylation levels.

Tissue plasminogen activator (tPA) is the only available treatment for acute stroke. In addition to its vascular fibrinolytic action, tPA exerts various effects within the brain, ranging from synaptic plasticity to control of cell fate. To date, the influence of tPA in the ischemic brain has only been investigated on neuronal, microglial, and endothelial fate. We addressed the mechanism of action of tPA on oligodendrocyte (OL) survival and on the extent of white matter lesions in stroke. We also investigated the impact of aging on these processes. We observed that, in parallel to reduced levels of tPA in OLs, white matter gets more susceptible to ischemia in old mice. Interestingly, tPA protects murine and human OLs from apoptosis through an unexpected cytokine-like effect by the virtue of its epidermal growth factor-like domain. When injected into aged animals, tPA, although toxic to the gray matter, rescues white matter from ischemia independently of its proteolytic activity. These studies reveal a novel mechanism of action of tPA and unveil OL as a target cell for cytokine effects of tPA in brain diseases. They show overall that tPA protects white matter from stroke-induced lesions, an effect which may contribute to the global benefit of tPA-based stroke treatment., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

America Latina ha vivido en los ultimos diez anos cambios sociales importantes,revelados al contrastar las plataformas politicas actuales con las vigentes en las decadas de 1980 y 1990. En el ambito de la politica monetaria, empero, parece haber una continuidad de la perspectiva monetarista centrada en la estabilizacion de la moneda y el control de la inflacion. Como intento de hacer frente al estancamiento relativo del pensamiento social latinoamericano contemporaneo acerca de los origenes de la inflacion y las formas de encararla, el presente trabajo se propone a revisar el aporte de la concepcion estructuralista y su entendimiento de la tendencia al aumento del nivel general de precios que acomete la region, considerando especialmente la contribucion del economista mexicano Juan Noyola Vasquez.