Biosíntesis de un lípido-trisacárido intermediario en animales superiores : Papel en la biosíntesis de glicoproteínas

En el presente trabajo se estudió la síntesis de un lípido-trisacárido y su papel en la biosíntesis de la porción azúcar de las glicoproteínas. Se pueden considerar tres aspectos en esta investigación: Biosíntesis del Dolicol-P-P-N-acetilglucosamina. Microsomas de oviducto de gallina incubados con dolicol-P, Mg++, detergente y UDP 14C GlcNac catalizan la transferencia de la GlcNac a un compuesto soluble en la fracción lipídica. Por hidólisis ácida suave del lípido-azúcar, seguida de cromatografía en papel, se obtiene unicamente 14C GlcNac. La formación del lípido- de N-acetilglucosamina se incrementa por la adición de cantidadas crecientes de dolicol-P. Se estudiaron también las condiciones óptimas de incubación. Se compararon estos resultados con los obtenidos a partir de microsomas de hígado de rata. Biosíntesis del Dolico-P-P-di-N-acetilquitobiosa. lncubando dolicol-P-P-N-acetilglucosamina radioactivo y UDPGIcNac, no marcado, con microsomas de oviducto de gallina, en presencia de Mg++ y detergente, se obtiene la formación de un nuevo lípidoazúcar. Este nuevo compuesto es lábil al tratamiento ácido suave y el resto hidrofílico fue identificado por cromatografía en papel y por digestión con β-N-acetilglucosaminidasa como la di-N-acetilquitobiosa (2-acetoamido-2deoxi-0- β -D-glucopiranosil-( 1-4)-2 acetoamido-2 deoxi-D-glucosa).Se estudió también la síntesis de este disacárido en distintos tejidos y las condiciones óptimas para obtener un mejor rendimiento. Se presentan evidencias de que este lípido-disacárido, al igual que el de GlcNac son derivados del dolicol-pirofosfato. La biosíntesis de estos dos lípido-azúcares había sido descripta anteriormente en este Instituto, (110), con preparaciones de microsomas de hígado. Biosíntesis del lípido-trisácarido. Manosa puede ser transferida desde guanosina difosfato manosa al dolicol-P-P-di-N-acetilquitobiosa cuando estos sustratos se incuban con microsomas de oviducto de gallina en presencia de Mg++ y detergente. Por hidrólisis-ácida suave del compuesto formado se obtiene un oligosacárido que por cromatografía en papel con distintos solventes y por acción de diferentes glicosidasas parece ser el siguiente trísacarido: β-manosil-β-N-acetilglucosaminil-( 1-4)-N-acetilglucosamina. Se estudiaron las condiciones experimentales para la formación de este lípido-trisacárido. El lípido-trisacárido puede ser sintetizado con microsomas preparados a partir de otros tejidos. En ciertas condiciones experimentales se puede transferir más moléculas de manosa formándose un lípido-oligosacárido de mayor tamaño. Parte de estos resultados se han presentado en la IX y X Reunión Nacional de la Sociedad Argentina de Investigaciones Bioquímicas (151) (152) y han sido publicadas en el Biochemical and Biophysical Research Communications, (153)

Biochemical sysrematics of Menticirrhus americanus and Menticirrhus littoralis (Teleostel Perciformes: Sciaenidae)

Populations of two congeneric species of southwestern Atlantic sciaenid fish, Menticirrhus americanus and Menticirrhus littoralis, analysed electrophoretically to detect isoenzyme variability, showed very little genetic variation and a moderately high similarity in their allelic composition. A total of 22 alleles encoded by 17 loci were observed. Interspecific variability were found for the loci G6pdh-A, G6pdh-B, Hbdh-B, Mdh-B and Sod-A. Intraspecific variation was observed only for Mdh-B in M. littoralis. The genetic similarity between M. americanus and M. littoralis (INEI+0.76) is congruent with the high level of morphological similarity showed by these two congeneric species.Populações de duas espécies congenéricas de peixes cienídeos do Atlântico Sul-Oriental, Menticirrhus americanus e Menticirrhus littoralis, analisados eletroforeticamente para detectar a variabilidade isoenzimática, mostraram muito pouca variação genética e uma moderadamente alta similaridade em sua composição alélica. Um total de 22 alelos constituídos por 17 loci foram observados. Variabilidade interespecífica foi encontrada para os loci G6pdh-A, G6pdh-B, Hbdh-B, Mdh-B e Sod-A. Variação intraespecífica foi observada somente para Mdh-B em Aí. littoralis. A similaridade genética entre M. americanus e M. littoralis (INEI = 0,76) é congruente com o alto nível de similaridade morfológica mostrado por estas duas espécies congenéricas

Taxonomy of Causes, Impacts and Policy Responses to the Food Price Crisis in the Andean Region

This paper analyzes the causes, effects and policy alternatives associated with the recent international food price crisis in the Andean region. Additionally, the document makes a first approach to the policy options utilized to confront the crisis, discussing the mix of policies and their potential effectiveness, using a qualitative methodology based in part on schemes proposed in Manzano and Stein (2008), and Malarín (2008). A final section underscores various messages common to the countries of the region. Specifically, the report concludes that this crisis offers a great opportunity for transforming its uncertainties and costs into a stimulus for maturing an infrastructure of prevention and reduction of vulnerabilities in the Andean economies

FONA-7, a Novel Extended-Spectrum β-Lactamase Variant of the FONA Family Identified in Serratia fonticola

Serratia fonticola is a human pathogen widely found in the environment, with birds being reported as possible natural hosts. During an epidemiological and genomic surveillance study conducted to monitor the occurrence of extended-spectrum b-lactamase (ESBL)-producing Enterobacterales in South American wild birds, we identified an ESBL-positive S. fonticola in a fecal sample collected from a Hudsonian Whimbrel, during its non-breeding range on the Pacific Coast of Chile. Whole genome sequencing analysis and in silico modeling revealed a novel variant of the class A ESBLs FONA family, designated FONA-7, which shows 96.28% amino acid identity with FONA-6; with amino acid substitutions occurring in the signal peptide sequence (Thr22/Ser), and in the mature protein (Ser39/Asn and Thr227/Ile). This finding denotes that migratory birds can be potential vectors for the transboundary spread of ESBL-producing bacteria, creating a further theoretical riskfor the origin of novel plasmid-encoded b-lactamases.Fil: Fuentes Castillo, Danny. Universidade de Sao Paulo; BrasilFil: Power, Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Cerdeira, Louise. Universidade de Sao Paulo; BrasilFil: Cardenas-Arias, Adriana. Universidade de Sao Paulo; BrasilFil: Moura, Quézia. Universidade de Sao Paulo; BrasilFil: Oliveira, Flavio A.. Universidade Estadual de Campinas; BrasilFil: Levy, Carlos E.. Universidade Estadual de Campinas; BrasilFil: Gutkind, Gabriel Osvaldo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Catão-Dias, José L.. Universidade de Sao Paulo; BrasilFil: Lincopan, Nilton. Universidade de Sao Paulo; Brasi

Dissecting the Immune Stimulation Promoted by CSF-470 Vaccine Plus Adjuvants in Cutaneous Melanoma Patients: Long Term Antitumor Immunity and Short Term Release of Acute Inflammatory Reactants

As cutaneous melanoma (CM) currently remains with a bleak prognosis, thorough investigation of new treatment options are of utmost relevance. In the phase II/III randomized clinical trial (CASVAC-0401), the repeated immunization of stages IIB-III CM patients with the irradiated, allogeneic cellular CSF-470 vaccine plus the adjuvants bacillus Calmette-Guerin (BCG) and recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) demonstrated a significant benefit over IFN-alpha2B treatment in distant metastasis-free survival. Here we present on the short and long term immune monitoring results after completing the 2-year protocol; a continuation of the previous report by Mordoh et al. (1). We demonstrate that the repeated CSF-470 vaccinations stimulated a long term cellular and humoral immunity response directed against the vaccine antigens. In the case of 2 patients, we are able to show that a similar immune response was generated against autologous antigens. Evaluation of inhibitory receptor co-expression on patient's T cells indicates that the vaccination protocol did not stimulate T cell exhaustion. In order to better understand the basis for the efficacious vaccine responses observed, we investigated the short term immune events following vaccine injection. A significant increase in C-reactive protein (CRP) and IL-6 was observed 24 h after vaccination, with in vitro studies suggesting IL-6 production occurs in the vaccine site. We demonstrate that CRP enhances the cytotoxicity of peripheral blood mononuclear cells (PBMC) against melanoma cells in an in vitro model. Additionally, CRP stimulates the release of pro and anti-inflammatory cytokines from PBMC. As our results demonstrate that successive vaccinations with CSF-470 plus adjuvants promoted an increase in both anti-tumor innate and adaptive immunity, we propose a subsequent model of action

CD137 Is Expressed in Follicular Dendritic Cell Tumors and in Classical Hodgkin and T-Cell Lymphomas Diagnostic and Therapeutic Implications

CD137 (also known as 4-1BB and TNFRSF9) is a member of the tumor necrosis factor receptor superfamily. Originally identified as a costimulatory molecule expressed by activated T cells and NK cells, CD137 is also expressed by follicular dendritic cells, monocytes, mast cells, granulocytes, and endothelial cells. Anti-CD137 immunotherapy has recently shown promise as a treatment for solid tumors and lymphoid malignancies in preclinical models. We defined the expression of CD137 protein in both normal and neoplastic hematolymphoid tissue. CD137 protein is expressed by follicular dendritic cells in the germinal center and scattered paracortical T cells, but not by normal germinal-center B cells, bone marrow progenitor cells, or maturing thymocytes. CD137 protein is expressed by a select group of hematolymphoid tumors, including classical Hodgkin lymphoma, T-cell and NK/T-cell lymphomas, and follicular dendritic cells neoplasms. CD137 is a novel diagnostic marker of these tumors and suggests a possible target for tumor-directed antibody therapy

An Evaluation of the Contractionary Devaluation Hypothesis

Recent empirical and theoretical literature on the impact of real exchange rate devaluations on economic performance questions the traditional expansionary effect generated within standard Mundell-Fleming models. Contractionary devaluations may arise when firms face maturity or currency mismatches that, when faced with real exchange rate depreciations, lead to balance-sheet effects that erode firms' wealth and lead to an output contraction. While some authors show that the standard Mundell-Fleming result may hold even in the presence of currency mismatches, others point out that, if the balance sheet effect is large enough, devaluations can be contractionary. Using a large panel of 57 countries across the world and various newly constructed measures of dollarization, we test whether the balance sheet effect hypothesis has been relevant during the past decades in explaining economic downturns. Additionally, we explore the channels through which devaluations can be contractionary; in particular, we explore whether investment and consumption decisions are negatively affected by exchange rate devaluations under currency mismatches