Search

Background There are data suggesting that passive leg raising (PLR) improves hemodynamics during cardiopulmonary resuscitation (CPR). This trial aimed to determine the effectiveness and safety of PLR during CPR in out-of-hospital cardiac arrest (OHCA). Methods We conducted a randomized controlled trial with blinded assessment of the outcomes that assigned adults OHCA to be treated with PLR or in the flat position. The trial was conducted in the Camp de Tarragona region. The main end point was survival to hospital discharge with good neurological outcome defined as cerebral performance category (CPC 1–2). To study possible adverse effects, we assessed the presence of pulmonary complications on the first chest X-rays, brain edema on the computerized tomography (CT) in survivors and brain and lungs weights from autopsies in non-survivors. Results In total, 588 randomized cases were included, 301 were treated with PLR and 287 were controls. Overall, 67.8% were men and the median age was 72 (IQR 60–82) years. At hospital discharge, 3.3% in the PLR group and 3.5% in the control group were alive with CPC 1–2 (OR 0.9; 95% CI 0.4–2.3, p = 0.91). No significant differences in survival at hospital admission were found in all patients (OR 1.0; 95% CI 0.7–1.6, p = 0.95) and among patients with an initial shockable rhythm (OR 1.7; 95% CI 0.8–3.4, p = 0.15). There were no differences in pulmonary complication rates in chest X-rays [7 (25.9%) vs 5 (17.9%), p = 0.47] and brain edema on CT [5 (29.4%) vs 10 (32.6%), p = 0.84]. There were no differences in lung weight [1223 mg (IQR 909–1500) vs 1239 mg (IQR 900–1507), p = 0.82] or brain weight [1352 mg (IQR 1227–1457) vs 1380 mg (IQR 1255–1470), p = 0.43] among the 106 autopsies performed. Conclusion In this trial, PLR during CPR did not improve survival to hospital discharge with CPC 1–2. No evidence of adverse effects has been found. Clinical trial registration ClinicalTrials.gov: NCT01952197, registration date: September 27, 2013, https://clinicaltrials.gov/ct2/show/NCT01952197.

Total synthesis and structural confirmation of homo- and heterodimeric bispyrrolidinoindoline dioxopiperazine alkaloids isolated from fungi and bacteria, namely, ditryptoleucine A, ditryptoleucine B (11), the N,N′-bis-demethylated analogue (+)-12, (−)-dibrevianamide F (13), (−)-SF-5280-451 (14), tetratryptomycin A (15), (−)-tryprophenaline (17), and (−)-SF-5280-415 (18), has been carried out starting from the corresponding bispyrrolidinoindolines derived from tryptophan. Our efforts to synthesize all possible diastereomers of the natural ditryptoleucine isolates uncovered structural factors that determine the rate and efficiency of dioxopiperazine ring formation, leading in some cases to mixtures of diastereomers by concomitant epimerization, to the formation of their putative monomeric dioxopiperazine dipeptide biogenetic precursors, and to the alternative formation of a dimer with a fused 1,3,5-triazepan-6-one heterocycle. Financiado para publicación en acceso aberto: Universidade de Vigo/CISUG Ministerio de Economía y Competitividad | Ref. SAF2016-77620-R Xunta de Galicia | Ref. ED-431G/02 INBIOMED-FEDER Xunta de Galicia | Ref. ED431C 2017/61

Myelosuppression is the major dose-limiting toxicity of cancer chemotherapy. There have been many attempts to find new strategies that reduce myelosuppression. The dietary supplementation with lactic acid bacteria (LAB) improved respiratory innate immune response and the resistance against respiratory pathogens in immunosupressed hosts. Although LAB viability is an important factor in achieving optimal protective effects, non-viable LAB are capable of stimulating immunity. In this work, we studied the ability of oral preventive administration of viable and non-viable Lactobacillus rhamnosus CRL1505 or L. plantarum CRL1506 (Lr05, Lr05NV, Lp06V or Lp06NV, respectively) to minimize myelosuppressive and immunosuppressive effects derived from chemotherapy. Cyclophosphamide (Cy) impaired steady-state myelopoiesis in lactobacilli-treated and untreated control mice. Lr05V, Lr05NV and Lp06V treatments were the most effective to induce the early recovery of bone marrow (BM) tissue architecture, leukocytes, myeloid, pool mitotic and post-mitotic, peroxidase positive, and Gr-1Low/High cells in BM. We selected the CRL1505 strain for being the one capable of maintaining its myelopoiesis-enhancing properties in its non-viable form. Although the CRL1505 treatments do not modify the Cy ability to induce apoptosis, both increased the incorporation of BrdU in BM cells. Consequently, Lr05NV and Lr05V treatments were able to promote early recovery of LSK cells (Lin-Sca-1+c-Kit+ cells), multipotent progenitors (Lin-Sca-1+c-Kit+CD34+ cells), and myeloid cells (Gr-1+Ly6G+Ly6C- cells) with respect to the untreated Cy control. In addition, these treatments were able to increase the frequency of IL17A-producing innate lymphoid cells in the intestinal lamina propria (IL-17A+RORγt+CD4-NKp46+ cells) after Cy injection. These results were correlated with an increase in the IL-17A serum levels, a GM-CSF high expression and a CXCL12 lower expression in BM. Therefore, both Lr05V and Lr05NV treatments are able to activate beneficially the IL-17A/GM-CSF axis and accelerate the recovery of Cy-induced immunosuppression by increasing BM myeloid precursors. We demonstrated for the first time the beneficial effect of CRL1505 strain on myelopoiesis affected by a chemotherapeutic drug. Furthermore, Lr05NV could be a good and safe resource for reducing chemotherapy-induced leukopenia. The results are a starting point for future research and open up broad prospects for future applications of the immunobiotics.

Many attempts have been made to search for safer immunomodulatory agents that enhance the immune response and reduce the number and severity of infections in at-risk populations. The use of postbiotics, non-viable microbial cells or cell fractions that confer a health benefit to the consumer, represents a safe and attractive way to modulate and enhance the immune function in order to improve human health. Therefore, the aim of this work is to evaluate the immunoregulatory effect of Lactobacillus rhamnosus CRL1505 postbiotics in a complex culture system using human intestinal epithelial cells (IECs) and dendritic cells (DCs) differentiated from peripheral blood mononuclear cells. First, we demonstrated that L. rhamnosus CRL1505 differentially modulate human IECs and DCs after the challenge with the TLR4 agonist LPS. The CRL1505 strain down-regulated CD40, CD80 and CD86 expression in DCs, and increased their production of TNF-α, IL-1β, IL-6 and IL-10. Interestingly, the non-viable strain was able to modulate the immune response of both types of human cells. Then, we showed that cell wall (CW1505) and peptidoglycan (PG1505) from L. rhamnosus CRL1505 modulated TLR4-triggered immune response in IECs and DCs. Of interest, CW1505 showed a strong stimulatory effect while the PG1505 presented immune characteristics that were more similar to viable and non-viable CRL1505. To date, several molecules of immunobiotics were identified, that can be connected to specific host-responses. We hereby demonstrated that peptidoglycan of L. rhamnosus CRL1505 is a key molecule for the immunobiotic properties of this strain in human IECs and DCs. Likewise, the result of these studies could provide predictive tools for the in vivo efficacy of postbiotics and the scientific basis for their future applications in immunocompromised patients.

Hepatitis E is the major enterically transmitted viral hepatitis after hepatitis A. There are four known genotypes (GT) of the hepatitis E virus (HEV) affecting human beings. HEV GT1 causes outbreaks of acute hepatitis in developing countries of Africa and Asia, whereas HEV GT3 has been recognized as an emergent pathogen in industrialized countries characterized by zoonotic transmission and the possible development of chronic hepatitis in immunocompromised individuals. The aim of this work was to evaluate if the major antigen of HEV, the ORF2 capsid protein, can be used in combination with immunobiotic bacterium like particles (IBLP) for oral vaccination in a mouse model. We have cloned and expressed the RGS-His5-tagged HEV GT 3 capsid protein (ORF2) in E. coli and purified it by NiNTA under native and denaturing conditions. IBLP were prepared from two immunobiotic Lactobacillus rhamnosus strains by heat and acid treatments. Two different doses of protein were combined with IBLP and orally administered to Balb/c mice. After three oral immunizations separated for 14-day intervals, blood, intestinal fluid, Peyer´s patches and spleen samples were drawn. IgA and IgG specific antibodies were determined by ELISA. Mononuclear cell populations were analyzed by flow cytometry, and the cytokine profiles of isolated cells stimulated with ORF2 were determined by ELISA on the supernatants.Orally administered recombinant ORF2 protein combined with IBLP from two L. rhamnosus strains (CRL1505 and IBL027) induced both antigen specific humoral and cellular immune responses in mice. Interestingly, the adjuvant particles showed different behaviors, being BLP027 more effective inducing specific secretory IgA in the gut lumen. IFN-ɣ, TNF-ɑ and IL-4 were produced by Peyer?s plaques lymphocytes stimulated with the capsid antigen ex vivo suggesting a mixed Th1/Th2-type adaptive immune response in immunized mice.Oral vaccines are attractive because they are not invasive, do not need to be administered by specialized personal and, most important, elicit both systemic and local immune responses at the port of entry of the pathogens. Here we present a promising experimental oral vaccine for HEV genotype 3, which could be further developed for human and/or veterinary use. Fil: Arce, Lorena Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Medicina. Departamento Biomédico. Cátedra de Orientación Genética; Argentina Fil: Raya Tonetti, María Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Medicina. Departamento Biomédico. Cátedra de Orientación Genética; Argentina Fil: Raimondo, María Paula. Universidad Nacional de Tucumán. Facultad de Medicina. Departamento Biomédico. Cátedra de Orientación Genética; Argentina Fil: Müller, Melisa Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Medicina. Departamento Biomédico. Cátedra de Orientación Genética; Argentina Fil: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Baiker, Armin. Bavarian Health and Food Safety Authority; Alemania Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Vizoso Pinto, María Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Medicina. Departamento Biomédico. Cátedra de Orientación Genética; Argentina

We investigated whether the ability of commensal respiratory bacteria to modulate the innate immune response against bacterial and viral pathogens was a shared or strain-specific characteristic. Bacterial strains belonging to the Corynebacterium pseudodiphtheriticum and Dolosigranulum pigrum species were compared by studying their influence in the Toll-like receptor (TLR)-2- and TLR3-triggered immune responses in the respiratory tract, as well as in the resistance to Respiratory Syncytial Virus (RSV) and Streptococcus pneumoniae infections. We demonstrated that nasally administered C. pseudodiphteriticum 090104 or D. pigrum 040417 were able to modulate respiratory immunity and increase the resistance against pathogens, while other strains of the same species did not influence the respiratory immune responses, demonstrating a clear strain-dependent immunomodulatory effect of respiratory commensal bacteria. We also reported here that bacterium-like particles (BLP) and cell walls derived from immunomodulatory respiratory commensal bacteria are an interesting alternative for the modulation of the respiratory immune system. Our study is a step forward in the positioning of certain strains of respiratory commensal bacteria as next-generation probiotics for the respiratory tract. Fil: Ortiz Moyano, Francisco Ramiro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Raya Tonetti, María Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Medicina; Argentina Fil: Tomokiyo, Mikado. Tohoku University; Japón Fil: Kanmani, Paulraj. Dongguk University; Corea del Sur Fil: Vizoso Pinto, María Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Medicina; Argentina Fil: Kim, Hojun. Dongguk University; Corea del Sur Fil: Quilodrán Vega, Sandra. Universidad de Concepción; Chile Fil: Melnikov, Vyacheslav. Gabrichevsky Research Institute; Rusia Fil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Takahashi, Hideki. Tohoku University; Japón Fil: Kurata, Shoichiro. Tohoku University; Japón Fil: Kitazawa, Haruki. Tohoku University; Japón Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Tohoku University; Japón

7 pages, 3 figures, Background: The term chlorophyll c encompasses a small but heterogeneous group of algal pigments, characterized for being porphyrins rather than chlorins. Chlorophylls c are protochlorophyllide-type compounds that differ in their peripheral substituents. Mass spectrometry has contributed to the structural elucidation of chlorophylls c, often in parallel with the development of soft ionization techniques, Objective: To provide comprehensive information on the structural characterization of chlorophylls c by mass spectrometry, Method: A detailed exam of the existing bibliography from both the chemical and marine science literatures followed by the analysis of data on molecular masses and product ions. Previous tandem mass spectra of chlorophyll c pigments are reproduced employing high resolution mass spectrometry., Results: This article reviews the application of direct and tandem mass spectrometry techniques to the analysis of acidic and esterified chlorophylls c, summarizes their fragmentation patterns and enumerates some experimental fragmentation rules for their identification. The high resolution mass spectra of acidic and esterified chlorophyll c compounds are shown as characteristic examples., Conclusion: The combined information on the molecular mass and diagnostic fragmentation allows the unambiguous characterization of the known acidic chlorophylls c, including the discrimination of isomeric pigments. Tandem mass spectrometry is a technique of choice for the study of galactolipid-esterified chlorophylls c, as the systematic fragmentation of successive parts in the molecules allows good tentative approaches to their structures., This work is a contribution of Microalgas Nocivas, IEO, Unidad Asociada al IIM (CSIC) and was funded by MINECO-Spain (CTM2012-32181). A.G-O. acknowledges financial support from MINECO (Doctoral Grant No. BES-2013-065752).

Las regiones utilizadas en identificacion genetica son las no sensibles o no codificantes; es decir, aquellas que no proporcionan informacion sensible del individuo. Asi lo establece expresamente el art. 4 de la LO 10/2007, reguladora de las bases de datos policiales, que circunscribe la identificacion genetica a la utilizacion de este ADN llamado >. Las regiones no codificantes, si bien unidas funcionan como un codigo de barras de una persona, por si solas no ofrecen informacion de como es o de como se comporta el individuo. Pero el ADN de esas muestras tambien cuenta con otras regiones codificantes, llenas de informacion. Y es ahi donde la genetica forense tiene su mayor campo de extension; la > de los laboratorios forenses: el fenotipado forense . Basicamente, lo que pretende esta tecnica es predecir el aspecto humano a partir de una muestra de ADN hallada en la escena del delito a fines de investigacion criminal. La ciencia ha avanzado lo suficiente como para que los forenses puedan elaborar un retrato robot aproximado de una persona a partir de una pequena muestra de ADN.

Chemical compounds can be represented as attributed graphs. An attributed graph is a mathematical model of an object composed of two types of representations: nodes and edges. Nodes are individual components, and edges are relations between these components. In this case, pharmacophore-type node descriptions are represented by nodes and chemical bounds by edges. If we want to obtain the bioactivity dissimilarity between two chemical compounds, a distance between attributed graphs can be used. The Graph Edit Distance allows computing this distance, and it is defined as the cost of transforming one graph into another. Nevertheless, to define this dissimilarity, the transformation cost must be properly tuned. The aim of this paper is to analyse the structural-based screening methods to verify the quality of the Harper transformation costs proposal and to present an algorithm to learn these transformation costs such that the bioactivity dissimilarity is properly defined in a ligand-based virtual screening application. The goodness of the dissimilarity is represented by the classification accuracy. Six publicly available datasets—CAPST, DUD-E, GLL&GDD, NRLiSt-BDB, MUV and ULS-UDS—have been used to validate our methodology and show that with our learned costs, we obtain the highest ratios in identifying the bioactivity similarity in a structurally diverse group of molecules.

Computer-aided design (CAD) applications are paramount tools to inspect piping and instrumentation diagrams (P&ID) that represent the structure and functionality of oil and gas facilities. These tools allow engineers to navigate along the P&IDs and facilitate their inspection and maintenance tasks. Usually, these applications allow the user to search components for their identity or label. For instance, searching component I D − 2354 or the components with V a l v e label. Nevertheless, sometimes, engineers wish to search for a group of components that has a specific structure or similar to it. For example, they want to detect the appearances of structures that include a v a l v e c h e c k connected to two g e n e r a l v a l v e s and a b u t t e r f l y v a l v e . This paper proposes a method, based on the graph matching theory, that solves this problem. The computational complexity to detect the appearance of a component in a P&ID is linear with respect to the number of components whereas the computational complexity to detect similar structures is exponential. For this reason, heuristic algorithms have to be used. The aim of this work is to add this functionality to a CAD application.

Non-viable lactic acid bacteria (LAB) have been proposed as antigen delivery platforms called bacterium-like particles (BLPs). Most studies have been performed with Lactococcus lactis-derived BLPs where multiple antigens were attached to the peptidoglycan surface and used to successfully induce specific immune responses. It is well-established that the immunomodulatory properties of LAB are strain dependent and therefore, the BLPs derived from each individual strain could have different adjuvant capacities. In this work, we obtained BLPs from immunomodulatory (immunobiotics) and non-immunomodulatory Lactobacillus rhamnosus and Lactobacillus plantarum strains and comparatively evaluated their ability to improve the intestinal and systemic immune responses elicited by an attenuated rotavirus vaccine. Results demonstrated that orally administered BLPs from non-immunomodulatory strains did not induce significant changes in the immune response triggered by rotavirus vaccine in mice. On the contrary, BLPs derived from immunobiotic lactobacilli were able to improve the levels of anti-rotavirus intestinal IgA and serum IgG, the numbers of CD24+B220+ B and CD4+ T cells in Peyer's patches and spleen as well as the production of IFN-γ by immune cells. Interestingly, among immunobiotics-derived BLPs, those obtained from L. rhamnosus CRL1505 and L. rhamnosus IBL027 enhanced more efficiently the intestinal and systemic humoral immune responses when compared to BLPs from other immunobiotic bacteria. The findings of this work indicate that it is necessary to perform an appropriate selection of BLPs in order to find those with the most efficient adjuvant properties. We propose the term Immunobiotic-like particles (IBLPs) for the BLPs derived from CRL1505 and IBL027 strains that are an excellent alternative for the development of mucosal vaccines.

This chapter provides a review of the knowledge of the positive effects of immunobiotic lactic acid bacteria (LAB) on the modulation of respiratory antiviral immunity and their impact on the resistance to viral infections is provided. Pandemics and severe epidemics caused by respiratory viruses have challenged global health systems more than once. Respiratory viral infections are implicated in approximately 50% of community-acquired pneumonia in young children and over 90% of bronchiolitis cases in infants and young children seeking medical attention. In order to understand the effect of beneficial bacteria on viral respiratory infections, it is necessary to remember first some of the immunological mechanisms that are activated in the respiratory tract when a viral attack occurs. Most research regarding the beneficial effects of LAB on viral respiratory infections have focused on influenza virus. Secondary bacterial pneumonia is a severe complication responsible for the high morbidity and mortality associated with viral respiratory infections in high-risk population.

Retinoid X receptors (RXRs) are promiscuous partners of heterodimeric associations with other members of the Nuclear Receptor (NR) superfamily. Through these liaisons RXR ligands (“rexinoids”) either transcriptionally activate on their own the “permissive” subclass of heterodimers (PPAR/RXR, LXR/RXR, FXR/RXR) or synergize with partner ligands in the “non-permissive” subclass of heterodimers (RAR/RXR, VDR/RXR and TR/RXR). The nature and extent of the interaction of the ligand-receptor complexes with co-regulators, which is cell and context-dependent, results ultimately in transcriptional modulation of cognate gene networks. RXR modulators hold therapeutical potential for the treatment of cancer and other diseases related to nutrient acquisition and disposal, among them metabolic diseases. A rexinoid (bexarotene) has indeed reached the clinic for the treatment of cutaneous T-cell lymphoma. The modulation of RXR function by rexinoids acting as agonists, parcial agonists, inverse agonists or antagonists is encoded in the structure of the ligandreceptor complexes. A very large number of rexinoids with a wide structural diversity has been published. In addition to natural products and other ligands discovered by HTS or mere serendipity, most rexinoids have been rationally designed based on the structures of existing complexes with RXR determined by X-Ray or based on Molecular Modeling. Although the structural rationale for the modulation of the ligand-receptor complexes is reasonably well understood, it has not yet been possible to predict the correlation between ligand structure and physiological response, particularly in the case of heterodimer-selective rexinoids.

Mice heterozygously deficient for the myelin protein P 0 gene (P 0 +/−) develop a slowly progressing neuropathy modeling demyelinating Charcot-Marie-Tooth disease (CMT1B). The aim of the study was to investigate the long-term progression of motor dysfunction in P 0 +/− mice at 3, 7, 12 and 20 months. By comparison with WT littermates, P 0 +/− showed a decreasing motor performance with age. This was associated with a progressive reduction in amplitude and increase in latency of the plantar compound muscle action potential (CMAP) evoked by stimulation of the tibial nerve at ankle. This progressive functional impairment was in contrast to the mild demyelinating neuropathy of the tibial nerve revealed by histology. “Threshold-tracking” studies showed impaired motor axon excitability in P 0 +/− from 3 months. With time, there was a progressive reduction in threshold deviations during both depolarizing and hyperpolarizing threshold electrotonus associated with increasing resting I/V slope and increasing strength-duration time constant. These depolarizing features in excitability in P 0 +/− as well as the reduced CMAP amplitude were absent in P 0 +/− Na V 1.8 knockouts, and could be acutely reversed by selective pharmacologic block of Na V 1.8 in P 0 +/−. Mathematical modeling indicated an association of altered passive cable properties with a depolarizing shift in resting membrane potential and increase in the persistent Na + current in P 0 +/−. Our data suggest that ectopic Na V 1.8 expression precipitates depolarizing conduction failure in CMT1B, and that motor axon dysfunction in demyelinating neuropathy is pharmacologically reversible.

Objective: Intestinal intraepithelial lymphocytes (IELs) play critical roles in disrupting epithelial homeostasis after Toll-like receptor (TLR)-3 activation with genomic rotavirus dsRNA or the synthetic dsRNA analog poly(I:C). The capacity of immunobiotic Lactobacillus rhamnosus CRL1505 (Lr1505) or Lactobacillus plantarum CRL1506 (Lp1506) to beneficially modulate IELs response after TLR3 activation was investigated in vivo using a mice model. Results: Intraperitoneal administration of poly(I:C) induced inflammatory-mediated intestinal tissue damage through the increase of inflammatory cells (CD3+NK1.1+, CD3+CD8αα+, CD8αα+NKG2D+) and pro-inflammatory mediators (TNF-α, IL-1β, IFN-γ, IL-15, RAE1, IL-8). Increased expression of intestinal TLR3, MDA5, and RIG-I was also observed after poly(I:C) challenge. Treatment with Lr1505 or Lp1506 prior to TLR3 activation significantly reduced the levels of TNF-α, IL-15, RAE1, and increased serum and intestinal IL-10. Moreover, CD3+NK1.1+, CD3+CD8αα+, and CD8αα+NKG2D+ cells were lower in lactobacilli-treated mice when compared to controls. The immunomodulatory capacities of lactobacilli allowed a significant reduction of intestinal tissue damage. Conclusions: This work demonstrates the reduction of TLR3-mediated intestinal tissue injury by immunobiotic lactobacilli through the modulation of intraepithelial lymphocytes response. It is a step forward in the understanding of the cellular mechanisms involved in the antiviral capabilities of immunobiotic strains. Fil: Tada, Asuka. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Tohoku University. Graduate School of Agricultural Science. Food and Feed Immunology Group; Japón Fil: Zelaya, María Hortensia del Rosario. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Bioquímica Clinica I; Argentina Fil: Clua, Maria Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Alvarez, Gladis Susana. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Bioquímica Clinica I; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Kitazawa, Haruki. Tohoku University. Graduate School of Agricultural Science. Food and Feed Immunology Group; Japón Fil: Villena, Julio Cesar. Tohoku University. Graduate School of Agricultural Science. Food and Feed Immunology Group; Japón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina

Oil & Gas facilities are extremely huge and have complex industrial structures that are documented using thousands of printed sheets. During the last years, it has been a tendency to migrate these paper sheets towards a digital environment, with the final end of regenerating the original computer-aided design (CAD) projects which are useful to visualise and analyse these facilities through diverse computer applications. Usually, this was done manually by re-sketching each page using CAD applications. Nevertheless, some applications have appeared which generate the CAD document automatically given the paper sheets. In this last case, the final document is always verified by an engineer due to the need of being a zero-error process. Since the need of an engineer is absolutely accepted, we present a new method to reduce the required engineer working time. This is done by highlighting the digitised components in the CAD document that the automatic method could have incorrectly identified. Thus, the engineer is required only to look at these components. The experimental section shows our method achieves a reduction of approximately 40% of the human effort keeping a zero-error process.

This paper presents an on-line learning method to automatically deduce the insertion, deletion and substitution costs of the graph edit distance, which is inspired in a previously published off-line learning method. The original method is based on embedding the ground-truth node-to-node mappings into a Euclidean space and learning the edit costs through the hyper-plane in this new space that splits the nodes into the mapped ones and the non-mapped ones. The new method has the advantage of learning the edit costs and computing the graph edit distance can be done simultaneously. Experimental validation shows that the matching accuracy is competitive with the off-line method but without the need of the whole learning set.

Spanish Abstract: En el presente trabajo se valora una opcion call estandar y una opcion call asiatica promedio aritmetico europea estrike fijo, asumiendo que el movimiento Browniano se ajusta a una distribucion logistica. Los resultados obtenidos se comparan con los obtenidos cuando se asume que el movimiento Browniano sigue una distribucion normal. El metodo numerico estocastico utilizado es Euler Maruyama, por ser un metodo simple. Dado que la opcion asiatica no tiene una solucion explicita, se simulan 10.000 trayectorias con particiones de 2^(-12) y se hace uso de la medida de riesgo neutral. Los resultados obtenidos muestran una consistencia con los obtenidos con un movimiento Browniano ajustado a una distribucion normal, en el sentido que el valor de la call de la opcion estandar es superior al valor de la opcion call asiatica promedio aritmetico, ademas se observa como lo sugiere la teoria una subvaloracion del precio de la opcion estandar cuando se asume normalidad frente a cuando se asume una distribucion logistica. English Abstract: In this paper, a standard call option and a fixed arithmetic European average call option are evaluated, assuming that the Brownian movement adjusts to a logistic distribution. The findings are compared with those obtained when it is assumed that the Brownian movement follows a normal distribution. The stochastic numerical method used is Euler Maruyama. Since the Asian option does not have an explicit solution, 10,000 trajectories with partitions of 2^(-12) are simulated and the neutral risk measure is used. The results obtained show a consistency with those obtained with a Brownian movement adjusted to a normal distribution, in the sense that the call value of the standard option is higher than the value of the arithmetic average Asian call option. In addition, as it is suggested by the theory we observe a price undervaluation of the standard option when normality is assumed compared with the case in which a logistic distribution is assumed.

Spanish Abstract: En el presente trabajo se valora una opcion call estandar y una opcion call asiatica promedio aritmetico europea estrike fijo, usando por primera vez el metodo numerico estocastico de Taylor 1.5. Los resultados obtenidos se comparan con los metodos numericos estocasticos de Euler-Maruyama y Milstein. Para ello se simulan 10.000 trayectorias con particiones de 2−12 y se hace uso de la medida de riesgo neutral. Los resultados obtenidos con Taylor 1.5 frente a los metodos de Euler- Maruyama y Milstein son practicamente los mismos, presentando un mayor costo computacional por su estructura el metodo de Taylor estocastico 1.5, seguido por Milstein y Euler-Maruyama. English Abstract: In this paper, a standard call option and a fixed arithmetic European average arithmetic call option are evaluated, using a stochastic numerical method of Taylor 1.5. The results obtained are compared with Euler-Maruyama's and Milstein's stochastic numerical methods. To this end, 10,000 trajectories with partitions of 2−12 are simulated and the neutral risk measure is used. The results obtained with Taylor 1.5 compared to these of Euler-Maruyama and Milstein are pretty much the same, even though Taylor 1.5 has a higher computational cost due to its structure.

Graph edit distance has become an important tool in structural pattern recognition since it allows us to measure the dissimilarity of attributed graphs. One of its main constraints is that it requires an adequate definition of edit costs, which are application dependent. These costs eventually determine which graphs are considered similar or not in a concrete application. Several methods have been presented to learn these costs to avoid manually setting them. They are based on different techniques ranging from probabilistic methods to neural networks or known optimisation algorithms. The aim of this paper is twofold. On the one hand, we list them and summarize their features. On the other hand, we empirically analyse the behaviour of the proposed optimisation functions. We conclude that these functions return different edit costs and therefore, they have to be considered application dependent and not only a technicality of the method, as it has been considered so far.

The natural product tripartin has been reported to inhibit the N-methyl lysine histone demethylase KDM4A. A synthesis of tripartin starting from 3,5-dimethoxyphenylacrylic acid was developed and the enantiomers were separated by chiral HPLC. We observed that both tripartin enantiomers manifested an apparent increase in the H3K9me3 levels when dosed in cells, as measured by Western blot analysis. Thus, there is no enantiomeric discrimination towards this natural product in terms of its effects on cellular histone methylation status. Interestingly, tripartin did not inhibit isolated KDM4A-E under our assay conditions (IC50 > 100 μM). Tripartin analogues with a dichloromethylcarbinol group derived from the indanone scaffold were synthesized and found to be inactive against isolated recombinant KDM4 enzymes and in cell-based assays. Although the precise cellular mode of action of tripartin is unclear, our evidence suggests that it may affect histone methylation status via a mechanism other than direct inhibition of the KDM4 histone demethylases.

The rapid rise in microbiome and probiotic science has led to estimates of product creation and sales exceeding $50 billion within five years. However, many people do not have access to affordable products, and regulatory agencies have stifled progress. The objective of a discussion group at the 2017 meeting of the International Scientific Association for Probiotics and Prebiotics was to identify mechanisms to confer the benefits of probiotics to a largerportion of the world?s population. Three initiatives, built around fermented food, were discussed with different methods of targeting populations that face enormous challenges of malnutrition, infectious disease, poverty and violent conflict. As new candidate probiotic strains emerge, and the market diversifies towards more personalised interventions, manufacturing processes will need to evolve. Information dissemination through scientific channels and social media is projected to provide consumers and healthcare providers with rapid access to clinical results, and to identify the nearest location of sites making new and affordable probiotic food and supplements. This rapid translation of science to individual well-being will not only expand the beneficiaries of probiotics, but also fuel new social enterprises and economic business models. Fil: Reid, Gregor. University Of Western Ontario; Canadá Fil: Kort, Remco. Yoba For Life Foundation; Países Bajos. University of Amsterdam; Países Bajos Fil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina Fil: Bourdet-Sicard, Raphaelle. Danone Access, Africa & India, Danone Nutricia Research; Francia Fil: Benoit, Valérie. General Mills, Nutrition And Technology Solutions; Estados Unidos Fil: Cunningham, Melissa. Research And Development, Metagenics (aust) Pty Ltd.; Australia Fil: Saulnier, Delphine MA.. Novozymes; Dinamarca Fil: van Hylckama Vlieg, Johan ET.. Christian Hansen As; Dinamarca Fil: Verstraelen, Hans. Ghent University Hospital 0p4; Países Bajos Fil: Sybesma, Wilbert. Yoba For Life Foundation; Países Bajos

Peripheral nerve blocks (PNBs) using local anesthetic (LA) are superior to systemic analgesia for management of post-operative pain. An insufficiently short PNB duration following single-shot LA can be optimized by development of extended release formulations among which liposomes have been shown to be the least toxic. In vivo rodent models for PNB have focused primarily on assessing behavioral responses following LA. In a previous study in human volunteers, we found that it is feasible to monitor the effect of LA in vivo by combining conventional conduction studies with nerve excitability studies. Here, we aimed to develop a mouse model where the same neurophysiological techniques can be used to investigate liposomal formulations of LA in vivo. To challenge the validity of the model, we tested the motor PNB following an unilamellar liposomal formulation, filled with the intermediate-duration LA lidocaine. Experiments were carried out in adult transgenic mice with fluorescent axons and with fluorescent tagged liposomes to allow in vivo imaging by probe-based confocal laser endomicroscopy. Recovery of conduction following LA injection at the ankle was monitored by stimulation of the tibial nerve fibers at the sciatic notch and recording of the plantar compound motor action potential (CMAP). We detected a delayed recovery in CMAP amplitude following liposomal lidocaine, without detrimental systemic effects. Furthermore, CMAP threshold-tracking studies of the distal tibial nerve showed that the increased rheobase was associated with a sequence of excitability changes similar to those found following non-encapsulated lidocaine PNB in humans, further supporting the translational value of the model.

Retinoid receptors (RARs and RXRs) transduce the signals of their natural and synthetic ligands (retinoids and rexinoids) to cellular transcriptional machinery to induce gene programs that control diverse biological and physiological effects on organisms. All-trans-retinoic acid, the natural ligand for RARs, is used therapeutically for the treatment of acute promyelocytic leukemia (APL), whereas the synthetic rexinoid bexarotene (a representative member of the aromatic retinoids or arotinoids) is approved for the treatment of cutaneous T-cell lymphoma (CTCL). Other retinoids have found applications in the topical treatment of skin disorders. In continuation of previous work on the naphthalene-based arotinoid scaffold, we synthesized a new series of (3-halo)benzoic acids connected to C5- or C8-substituted naphthyl rings via (E)-ethenyl and amide and, for the C5 series, (E)-chalcone linkers. These compounds were evaluated as RAR modulators in comparison with previously described dihydronaphthalene arotinoids with the same substitution pattern. Transactivation studies in this series revealed an absence of synergy between small halogen atoms (F, Cl) at C3 and the groups at C5 or C8, as had been observed on some of the dihydronaphthalene analogues. Instead, non-halogenated 4-(2-naphthamido)benzoic acid derivatives transactivated toward the RARβ subtype in preference to the paralogues. The derivatives with bulkier substituents at C8 were characterized as dual RARβ/RARα antagonists, and (E)-4-[(8-(phenylethynyl)naphthalene-2-yl)ethenyl]benzoic acid (11 c), with an ethenyl connector, was shown to be a potent antagonist of RARα.

The genome sequence of the immunomodulatory strain Lactobacillus rhamnosus strain IBL027 is described here. The reads were assembled into contigs with a total size 2,898,501 bp. The genome information will be useful for further specific genetic studies of this strain to evaluate its immunomodulatory and biotechnological properties as a vaccine adjuvant.

The genome sequence of the immunomodulatory strain Lactobacillus rhamnosus strain IBL027 is described here. The reads were assembled into contigs with a total size 2,898,501 bp. The genome information will be useful for further specific genetic studies of this strain to evaluate its immunomodulatory and biotechnological properties as a vaccine adjuvant. Fil: Vizoso Pinto, María Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina Fil: Saavedra, Maria Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Hebert, Elvira Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Raya Tonetti, María Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Albarracín, Leonardo Miguel. Tohoku University; Japón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Kitazawa, Kitazawa. Tohoku University; Japón Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina

Bronchodilator test measures lung function performing spirometry before and after the administration of a fast-acting bronchodilator. Recent studies reflect variability among nurses in its performance. Aims: To know the context and how nurses are performing this test -To determine how drugs are administrated (dose and type) Methods: -Descriptive multicenter cross-sectional survey study in Madrid, Spain Results: N=58.A total of 63 responses were received Socio-demographic characteristics of the sample: -Place of work:(Figure 1)Functional lab testing (46%), outpatient setting(25%), community health(16%). -Experience:97% of participant have more than a year of experience performing the bronchodilator test -Drugs administration:Figure 2 Salbutamol 100μg: 4puff(45%), 2puff(31%), 2puff(22%) and 1puff(2%) Ipratropium 20 μg: 3puff(41%),2puff(30%) and 4puff(29%) Terbutaline 500 μg: 2 puff (85%), 1 puff(8%) and 4 puff(7%) -86% of nurses know how to interpret the test Conclusions: 46% of nurses work in a functional lab testing. 97% of them perform the bronchodilator test for more than a year and 86% of them know how to interpret it Regarding to drugs administration:Salbutamol 100 μg is administered in 4 puff by 45%of participants, Ipratropium 20 μg is used by 41% of nurses (3puff), and Terbutaline 500 μg is used administering 2puff by 85% of them 86% of nurses use a spacer for pressurized inhalers. 15 minutes are normally the waiting time to interpret the test Although there is great variability, most nurses follow SEPAR criteria

Immunobiotic lactic acid bacteria have become an interesting alternative for the prevention of respiratory infections. Previously, we demonstrated that the nasal administration of Lactobacillus rhamnosus CRL1505, during repletion of malnourished mice, resulted in diminished susceptibility to the challenge with the respiratory pathogen Streptococcus pneumoniae. Considering the known alterations induced by malnutrition on T lymphocytes and the importance of this cell population on the protection against respiratory pathogens, we aimed to study the effect of L. Rhamnosus CRL1505 nasal administration on the recovery of T cell-mediated defences against pneumococcal infection in malnourished mice under nutritional recovery. Malnourished mice received a balanced conventional diet (BCD) for seven days or BCD for seven days with nasal L. Rhamnosus CRL1505 supplementation during last two days of the treatment. After the treatments mice were infected with S. Pneumoniae. Flow cytometry studies were carried out in bone marrow, thymus, spleen and lung to study T cells, and Th1/Th2 cytokine profiles were determined in broncho-alveolar lavages and serum. The administration of CRL1505 strain to malnourished mice under recovery reduced quantitative and qualitative alterations of CD4+ T cells in the bone marrow, thymus, spleen and lung induced by malnutrition. In addition, CRL1505 treatment augmented Th2- cytokines (interleukin 10 and 4) in respiratory and systemic compartments after pneumococcal infection. These results show that modulation of CD4+ T lymphocytes induced by L. Rhamnosus CRL1505 has an important role in the beneficial effect induced by this strain on the recovery of malnourished mice. These data also indicate that nasally administered L. Rhamnosus CRL1505 may represent a non-invasive alternative to modulate and improve the T cell-mediated immunity against respiratory pathogens in immunocompromised malnourished hosts. Fil: Barbieri, Natalia Paola del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Universidad Nacional de Chilecito; Argentina Fil: Herrera, Héctor Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina Fil: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina Fil: Alvarez, Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Universidad Nacional de Tucumán; Argentina

The present study evaluated the effect of nasally given Lactobacillus rhamnosus CRL1505 on the immunocoagulative response during pneumococcal infection in immunocompetent mice. In addition, we aimed to gain insight into the mechanism involved in the immunomodulatory effect of the L. rhamnosus CRL1505 strain by evaluating the role of TLR2. Results showed that nasally given L. rhamnosus CRL1505 effectively regulates inflammation and hemostatic alterations during the pneumococcal infection. Immunobiotic treatment significantly reduced permeability of the bronchoalveolar-capillary barrier, and general cytotoxicity, decreasing lung tissue damage. The CRL1505 strain improved the production of TNF-α, IFN-γ, and IL-10 after pneumococcal challenge. In addition, increased TM and TF expressions were found in lungs of L. rhamnosus CRL1505-treated mice. Moreover, we demonstrated, for the first time, that the TLR2 signaling pathway has a role in the induction of IFN-γ and IL-10 and in the reduction of TF. The results also allow us to speculate that a PRR, other than TLR2, may mediate the immunobiotic activity of L. rhamnosus CRL1505 and could explain changes in TNF-α and TM.

Arotinoids containing a C5,C8-diphenylnaphthalene-2-yl ring linked to a (C3-halogenated) benzoic acid via an ethenyl connector (but not the corresponding naphthamides), which are prepared by Horner-Wadsworth-Emmons reaction of naphthaldehydes and benzylphosphonates, display the rather unusual property of being RXR agonists (15-fold induction of the RXR reporter cell line was achieved at 3- to 10-fold lower concentration than 9-cis-retinoic acid) and RAR antagonists as shown by transient transactivation studies. The binding of such bulky ligands suggests that the RXR ligand-binding domain is endowed with some degree of structural elasticity.

The relationship between dysmyelination and the progression of neuropathy in Charcot-Marie-Tooth (CMT) hereditary polyneuropathy is unclear. Mice heterozygously deficient for the myelin protein P₀ gene (P₀+/-) are indistinguishable from wild-type (WT) at birth and then develop a slowly progressing demyelinating neuropathy reminiscent of CMT Type 1b. Accumulating evidence suggests that impulse conduction can become lethal to acutely demyelinated central and peripheral axons. Here we investigated the vulnerability of motor axons to long-lasting, high-frequency repetitive stimulation (RS) in P₀+/- mice as compared to WT littermates at 7, 12, and 20 months of age. RS was carried out in interrupted trains of 200 Hz trains for 3h. Tibial nerves were stimulated at the ankle while the evoked compound muscle action potentials (CMAPs) and the ascending compound nerve action potentials (CNAPs) were recorded from plantar muscles and the sciatic nerve, respectively. In 7-month old mice, there was recovery of CMAP and CNAP following RS. When mice were about one year old, electrophysiological recovery following RS was incomplete and in P₀+/- also associated with morphological signs of partial Wallerian degeneration. The effect of RS was larger in P₀+/- as compared to age-matched WT. When mice were about 2 years old, the effect was stronger and became similar between WT and P₀+/-. RS was followed by a transient hyperpolarization, which decreased with age and was smaller in P0+/- than in WT. Our data suggest that both aging and the dysmyelinating disease process may contribute to the susceptibility to activity-induced axonal degeneration. It is possible that in aging mice and in P₀+/- there is inadequate energy-dependent Na(+)/K(+) pumping, as indicated by the reduced post-stimulation hyperpolarization, which may lead to a lethal Na(+) overload in some axons.

4 páginas, 3 figuras, The controversial molecular identification of the so-called chlorophyll cCS–170 has been settled. Despite its relevance as a potential biomarker in the study of eukaryotic picophytoplankton, the structure of this chlorophyll remained so far uncertain. A full characterization by NMR, UV–vis, and ESI-MS is reported, revealing this chlorophyll as [7-methoxycarbonyl-8-vinyl]-protochlorophyllide a., The authors wish to acknowledge the financial support from the Isidro Parga Pondal Program (Xunta de Galicia, Spain) to B.V. and the funding from the European Union Seventh Framework Programme [FP7/REGPOT-2012-2013.1] under Grant Agreement No. 316265, BIOCAPS. This work was partly supported by Xunta de Galicia through project Incite09 402 253PR.

The vertebrate circulatory system is the most complex vascular system among those of metazoans, with key innovations including a multi-chambered heart and highly specialized blood cells. Invertebrate vessels, on the other hand, consist of hemal spaces between the basal laminae of epithelia. How the evolutionary transition from an invertebrate-type system to the complex vertebrate one occurred is, however, poorly understood. We investigate here the development of the cardiovascular system of the cephalochordate amphioxus Branchiostoma lanceolatum in order to gain insight into the origin of the vertebrate cardiovascular system. The cardiac markers Hand, Csx (Nkx2-5) and Tbx4/5 reveal a broad cardiac-like domain in amphioxus; such a decentralized organization during development parallels that seen in the adult anatomy. Our data therefore support the hypothesis that amphioxus never possessed a proper heart, even transiently during development. We also define a putative hematopoietic domain, supported by the expression of the hematopoietic markers Scl and Pdvegfr. We show that this area is closed to the dorsal aorta anlages, partially linked to excretory tissues, and that its development is regulated by retinoic acid, thus recalling the aorta-gonads-mesonephros (AGM) area of vertebrates. This region probably produces Pdvegfr+ hemal cells, with an important role in amphioxus vessel formation, since treatments with an inhibitor of PDGFR/VEGFR lead to a decrease of Laminin in the basal laminae of developing vessels. Our results point to a chordate origin of hematopoiesis in an AGM-like area from where hemal Pdvegfr+ cells are produced. These Pdvegfr+ cells probably resemble the ancestral chordate blood cells from which the vertebrate endothelium later originated.

Lactobacillus rhamnosus CRL1505 and Lactobacillus plantarum CRL1506 are immunobiotic strains able to increase protection against viral intestinal infections as demonstrated in animal models and humans. To gain insight into the host-immunobiotic interaction, the transcriptomic response of porcine intestinal epithelial (PIE) cells to the challenge with viral molecular associated pattern poly(I:C) and the changes in the transcriptomic profile induced by the immunobiotics strains CRL1505 and CRL1506 were investigated in this work. By using microarray technology and reverse transcription PCR, we obtained a global overview of the immune genes involved in the innate antiviral immune response in PIE cells. Stimulation of PIE cells with poly(I:C) significantly increased the expression of IFN-α and IFN-β, several interferon-stimulated genes, cytokines, chemokines, adhesion molecules, and genes involved in prostaglandin biosynthesis. It was also determined that lactobacilli differently modulated immune gene expression in poly(I:C)-challenged PIE cells. Most notable changes were found in antiviral factors (IFN-α, IFN-β, NPLR3, OAS1, OASL, MX2, and RNASEL) and cytokines/chemokines (IL-1β, IL-6, CCL4, CCL5, and CXCL10) that were significantly increased in lactobacilli-treated PIE cells. Immunobiotics reduced the expression of IL-15 and RAE1 genes that mediate poly(I:C) inflammatory damage. In addition, lactobacilli treatments increased the expression PLA2G4A, PTGES, and PTGS2 that are involved in prostaglandin E2 biosynthesis. L. rhamnosus CRL1505 and L. plantarum CRL1506 showed quantitative and qualitative differences in their capacities to modulate the innate antiviral immune response in PIE cells, which would explain the higher capacity of the CRL1505 strain when compared to CRL1506 to protect against viral infection and inflammatory damage in vivo. These results provided valuable information for the deeper understanding of the host-immunobiotic interaction and their effect on antiviral immunity. The comprehensive transcriptomic analyses successfully identified a group of genes (IFN-β, RIG1, RNASEL, MX2, A20, IL27, CXCL5, CCL4, PTGES, and PTGER4), which can be used as prospective biomarkers for the screening of new antiviral immunobiotics in PIE cells and for the development of novel functional food and feeds, which may help to prevent viral infections. Fil: Albarracín, Leonardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Tohoku University; Japón Fil: Kobayashi, Hisakazu. Tohoku University; Japón Fil: Iida, Hikaru. Tohoku University; Japón Fil: Sato, Nana. Tohoku University; Japón Fil: Nochi, Tomonori. Tohoku University; Japón Fil: Aso, Hisashi. Tohoku University; Japón Fil: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina Fil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina Fil: Kitazawa, Haruki. Tohoku University; Japón Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina

The extraction of spatio-chromatic features from color images is usually performed independently on each color channel. Usual 3D color spaces, such as RGB, present a high inter-channel correlation for natural images. This correlation can be reduced using color-opponent representations, but the spatial structure of regions with small color differences is not fully captured in two generic Red-Green and Blue-Yellow channels. To overcome these problems, we propose new color coding that is adapted to the specific content of each image. Our proposal is based on two steps: (a) setting the number of channels to the number of distinctive colors we find in each image (avoiding the problem of channel correlation), and (b) building a channel representation that maximizes contrast differences within each color channel (avoiding the problem of low local contrast). We call this approach more-than-three color coding (MTT) to emphasize the fact that the number of channels is adapted to the image content. The higher the color complexity of an image, the more channels can be used to represent it. Here we select distinctive colors as the most predominant in the image, which we call color pivots, and we build the new color coding strategy using these color pivots as a basis. To evaluate the proposed approach, we measure the efficiency in an image categorization task. We show how a generic descriptor improves performance at the description level when applied to the MTT coding.

Biological activity of natural retinoids requires the oxidation of retinol to retinoic acid (RA) and its binding to specific nuclear receptors in target tissues. The first step of this pathway, the reversible oxidoreduction of retinol to retinaldehyde, is essential to control RA levels. The enzymes of retinol oxidation are NAD-dependent dehydrogenases of the cytosolic medium-chain (MDR) and the membrane-bound short-chain (SDR) dehydrogenases/reductases. Retinaldehyde reduction can be performed by SDR and aldo-keto reductases (AKR), while its oxidation to RA is carried out by aldehyde dehydrogenases (ALDH). In contrast to SDR, AKR and ALDH are cytosolic. A common property of these enzymes is that they only use free retinoid, but not retinoid bound to cellular retinol binding protein (CRBP). The relative contribution of each enzyme type in retinoid metabolism is discussed in terms of the different subcellular localization, topology of membrane-bound enzymes, kinetic constants, binding affinity of CRBP for retinol and retinaldehyde, and partition of retinoid pools between membranes and cytoplasm. The development of selective inhibitors for AKR enzymes 1B1 and 1B10, of clinical relevance in diabetes and cancer, granted the investigation of some structure-activity relationships. Kinetics with the 4-methyl derivatives of retinaldehyde isomers was performed to identify structural features for substrate specificity. Hydrophilic derivatives were better substrates than the more hydrophobic compounds. We also explored the inhibitory properties of some synthetic retinoids, known for binding to retinoic acid receptors (RAR) and retinoid X receptors (RXR). Consistent with its substrate specificity towards retinaldehyde, AKR1B10 was more effectively inhibited by synthetic retinoids than AKR1B1. A RARβ/γ agonist (UVI2008) inhibited AKR1B10 with the highest potency and selectivity, and docking simulations predicted that its carboxyl group binds to the anion-binding pocket.

We studied the systemic effects of the intranasal administration of Lactobacillus casei on the immuno-coagulative response in pneumoccocal infection in immunocompromised mice. Weaned mice consumed a protein-free diet (PFD) for 21 days and were therefore malnourished. Malnourished mice were fed a balanced conventional diet (BCD) for 7 days (BCD group) or a BCD for 7 days with nasal administration of viable L. casei on days 6 and 7 (BCD+LcN group). The malnourished control mice (MNC) received a PFD, whereas the well-nourished control mice (WNC) continually consumed a BCD. At the end of the treatment period, the mice were infected with Streptococcus pneumoniae. At different times after infection, we analysed the following parameters: global coagulation system, activation of coagulation, coagulation inhibitors, platelet count, leukocyte count and myeloperoxidase (MPO) activity, total proteins, albumin and acute phase proteins (APPs). The MNC group showed greater impairment in the coagulation tests and an increase in the positive APPs. These parameters were normalized by the L. casei treatment. However, the number of leukocytes, decreased by malnutrition, was improved only by the administration of L. casei. After infection, the BCD+LcN group showed similar results to those of the WNC group for most of the haemostatic parameters. The BCD+LcN group did not show significant variations in the prothrombin time or in the level of anticoagulant protein C, but showed higher levels of fibrinogen, platelets, albumin, leukocytes and MPO activity compared with the different experimental groups. The intranasal administration of L. casei was effective in modulating the pro-inflammatory aspects of coagulation without affecting coagulation itself. Fil: Zelaya, María Hortensia del Rosario. Universidad Nacional de Tucuman. Facultad de Bioquimica, Quimica y Farmacia. Instituto de Bioquimica Clinica Aplicada. Catedra de Bioquimica Clinica I; Argentina; Fil: Laiño, Jonathan Emiliano. Universidad Nacional de Tucuman. Facultad de Bioquimica, Quimica y Farmacia. Instituto de Bioquimica Clinica Aplicada. Catedra de Bioquimica Clinica I; Argentina; Fil: Haro, Ana Cecilia. Universidad Nacional de Tucuman. Facultad de Bioquimica, Quimica y Farmacia. Instituto de Bioquimica Clinica Aplicada. Catedra de Bioquimica Clinica I; Argentina; Fil: Alvarez, Gladis Susana. Universidad Nacional de Tucuman. Facultad de Bioquimica, Quimica y Farmacia. Instituto de Bioquimica Clinica Aplicada. Catedra de Bioquimica Clinica I; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina; Fil: Agüero, Graciela. Universidad Nacional de Tucuman. Facultad de Bioquimica, Quimica y Farmacia. Instituto de Bioquimica Clinica Aplicada. Catedra de Bioquimica Clinica I; Argentina

Influenza virus (IFV) is a major respiratory pathogen of global importance, and the cause of a high degree of morbidity and mortality, especially in high-risk populations such as infants, elderly, and immunocompromised hosts. Given its high capacity to change antigenically, acquired immunity is often not effective to limit IFV infection and therefore vaccination must be constantly redesigned to achieve effective protection. Improvement of respiratory and systemic innate immune mechanisms has been proposed to reduce the incidence and severity of IFV disease. In the last decade, several research works have demonstrated that microbes with the capacity to modulate the mucosal immune system (immunobiotics) are a potential alternative to beneficially modulate the outcome of IFV infection. This review provides an update of the current status on the modulation of respiratory immunity by orally and nasally administered immunobiotics, and their beneficial impact on IFV clearance and inflammatory-mediated lung tissue damage. In particular, we describe the research of our group that investigated the influence of immunobiotics on inflammation-coagulation interactions during IFV infection. Studies have clearly demonstrated that hostile inflammation is accompanied by dysfunctional coagulation in respiratory IFV disease, and our investigations have proved that some immunobiotic strains are able to reduce viral disease severity through their capacity to modulate the immune-coagulative responses in the respiratory tract. Fil: Zelaya, María Hortensia del Rosario. Grupo de Investigación de Inmunobioticos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Aplicada; Argentina Fil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Grupo de Investigación de Inmunobioticos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Aplicada; Argentina Fil: Kitazawa, Haruki. Tohoku University; Japón Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Grupo de Investigación de Inmunobioticos; Argentina

UVI2008, a retinoic acid receptor (RAR) β/γ agonist originated from C3 bromine addition to the parent RAR pan-agonist 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid (TTNPB), is also a selective inhibitor of aldo-keto reductase family member 1B10 (AKR1B10). Thus, it might become a lead drug for the design of compounds targeting both activities, as an AKR1B10 inhibitor and RAR agonist, which could constitute a novel therapeutic approach against cancer and skin-related diseases. Herein, the X-ray structure of the methylated Lys125Arg/Val301Leu AKR1B10 (i.e. AKME2MU) holoenzyme in complex with UVI2008 was determined at 1.5 A resolution, providing an explanation for UVI2008 selectivity against AKR1B10 (IC50 = 6.1 μM) over the closely related aldose reductase (AR, IC50 = 70 μM). The carboxylic acid group of UVI2008 is located in the anion-binding pocket, at hydrogen-bond distance of catalytically important residues Tyr49 and His111. The inhibitor bromine atom can only fit in the wider active site of AKR1B10, mainly because of the native Trp112 side-chain orientation, not possible in AR. In AKR1B10, Trp112 native conformation, and thus UVI2008 binding, is facilitated through interaction with Gln114. IC50 analysis of the corresponding Thr113Gln mutant in AR confirmed this hypothesis. The elucidation of the binding mode of UVI2008 to AKR1B10, along with the previous studies on the retinoid specificity of AKR1B10 and on the stilbene retinoid scaffold conforming UVI2008, could indeed be used to foster the drug design of bifunctional antiproliferative compounds.

Lewis acid catalyzed Friedel–Crafts alkylation of indoles has been achieved in high yields and selectivities using p-quinols as electrophiles. (S)-Binol-3,3′-(9-anthracenyl)-phosphoric acid was able to catalyze the enantioselective formation of 5-(3-indole)-2-cyclohexenone derivatives. Experimental results and theoretical calculations explained the enantioselectivity based on a transition state where two water molecules act as a tether joining the p-quinol with the phosphoric acid and the NH of indole, thus facilitating the desymmetrization of the prochiral cyclohexadienone framework.

Mice deficient of myelin protein P 0 are established models of demyelinating Charcot-Marie-Tooth (CMT) disease. Dysmyelination in these mice is associated with an ectopic expression of the sensory neuron specific sodium channel isoform Na V 1.8 on motor axons. We reported that in P 0 +/−, a model of CMT1B, the membrane dysfunction could be acutely improved by a novel oral Na V 1.8 blocker referred to as Compound 31 (C31, Bioorg. Med. Chem. Lett. 2010, 20, 6812; AbbVie Inc.). The aim of this study was to investigate the extent to which C31 treatment could also improve the motor axon function in P 0 -/-, a CMT model with a much more severe neuropathy. We found that the progressive impairment of motor performance from 1 to 4 months of age in P 0 -/- could be acutely reversed by C31 treatment. The effect was associated with an improvement of the amplitude of the plantar CMAP evoked by tibial nerve stimulation. The corresponding motor nerve excitability studies by “threshold tracking” showed changes after C31 consistent with attenuation of a resting membrane depolarization. Our data suggest that the depolarizing motor conduction failure in P 0 -/- could be acutely improved by C31. This provides proof-of-concept that treatment with oral subtype-selective Na V 1.8 blockers could be used to improve the motor function in severe forms of demyelinating CMT.