Bacterial outer membrane vesicles and vaccine applications

Vaccines based on outer membrane vesicles (OMV) were developed more than 20 years ago against Neisseria meningitidis serogroup B. These nano-sized structures exhibit remarkable potential for immunomodulation of immune responses and delivery of “self” meningococcal antigens or unrelated antigens incorporated into the vesicle structure. This paper reviews different applications in OMV Research and Development (R&D) and provides examples of OMV developed and evaluated at the Finlay Institute in Cuba. A Good Manufacturing Practice (GMP) process was developed at the Finlay Institute to produce OMV from N. meningitidis serogroup B (dOMVB) using detergent extraction. Subsequently, OMV from N. meningitidis, serogroup A (dOMVA), serogroup W (dOMVW) and serogroup X (dOMVX) were obtained using this process. More recently, the extraction process has also been applied effectively for obtaining OMV on a research scale from Vibrio cholerae (dOMVC), Bordetella pertussis (dOMVBP), Mycobacterium smegmatis (dOMVSM) and BCG (dOMVBCG). The immunogenicity of the OMV have been evaluated for specific antibody induction, and together with functional bactericidal and challenge assays in mice have shown their protective potential. dOMVB has been evaluated with non-self neisserial antigens, including with a herpes virus type 2 glycoprotein, ovalbumin and allergens. In conclusion, OMV are proving to be more versatile than first conceived and remain an important technology for development of vaccine candidates. - See more at: http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00121/abstract#sthash.MwqUyZQ1.dpu

Neurochemical Characterization of the Tree Shrew Dorsal Striatum

The striatum is a major component of the basal ganglia and is associated with motor and cognitive functions. Striatal pathologies have been linked to several disorders, including Huntington’s, Tourette’s syndrome, obsessive–compulsive disorders, and schizophrenia. For the study of these striatal pathologies different animal models have been used, including rodents and non-human primates. Rodents lack on morphological complexity (for example, the lack of well defined caudate and putamen nuclei), which makes it difficult to translate data to the human paradigm. Primates, and especially higher primates, are the closest model to humans, but there are ever-increasing restrictions to the use of these animals for research. In our search for a non-primate animal model with a striatum that anatomically (and perhaps functionally) can resemble that of humans, we turned our attention to the tree shrew. Evolutionary genetic studies have provided strong data supporting that the tree shrews (Scadentia) are one of the closest groups to primates, although their brain anatomy has only been studied in detail for specific brain areas. Morphologically, the tree shrew striatum resembles the primate striatum with the presence of an internal capsule separating the caudate and putamen, but little is known about its neurochemical composition. Here we analyzed the expression of calcium-binding proteins, the presence and distribution of the striosome and matrix compartments (by the use of calbindin, tyrosine hydroxylase, and acetylcholinesterase immunohistochemistry), and the GABAergic system by immunohistochemistry against glutamic acid decarboxylase and Golgi impregnation. In summary, our results show that when compared to primates, the tree shrew dorsal striatum presents striking similarities in the distribution of most of the markers studied, while presenting some marked divergences when compared to the rodent striatum

Altered metabolic activity in the developing brain of rats predisposed to high versus low depression-like behavior

Individual differences in human temperament can increase risk for psychiatric disorders like depression and anxiety. Our laboratory utilized a rat model of temperamental differences to assess neurodevelopmental factors underlying emotional behavior differences. Rats selectively bred for low novelty exploration (Low Responders, LR) display high levels of anxiety- and depression-like behavior compared to High Novelty Responder (HR) rats. Using transcriptome profiling, the present study uncovered vast gene expression differences in the early postnatal HR versus LR limbic brain, including changes in genes involved in cellular metabolism. These data led us to hypothesize that rats prone to high (versus low) anxiety/depression-like behavior exhibit distinct patterns of brain metabolism during the first weeks of life, which may reflect disparate patterns of synaptogenesis and brain circuit development. Thus, in a second experiment we examined activity of Cytochrome C Oxidase (COX), an enzyme responsible for ATP production and a correlate of metabolic activity, to explore functional energetic differences in HR/LR early postnatal brain. We found that HR rats display higher COX activity in the amygdala and specific hippocampal subregions compared to LRs during the first 2 weeks of life. Correlational analysis examining COX levels across several brain regions and multiple early postnatal time points suggested desynchronization in the developmental timeline of the limbic HR versus LR brain during the first two postnatal weeks. These early divergent COX activity levels may reflect altered circuitry or synaptic activity in the early postnatal HR/LR brain, which could contribute to the emergence of their distinct behavioral phenotypes

Gestión competitiva: análisis de las MiPyMEs agroindustriales de primera transformación de La Pampa, Argentina

Las organizaciones del sector agroalimentario y agroindustrial son cruciales para el desarrollo de los países de Latinoamérica donde su gestión y desempeño tiene impactos multiplicadores socioeconómicos en los territorios. El objetivo de este trabajo es medir y evaluar la gestión competitiva de las MiPyMEs agroindustriales de primera transformación de la provincia de La Pampa, Argentina. Se entrevistaron a 59 de las 74 agroindustrias de la provincia, haciendo foco en 9 ejes y 54 factores de gestión competitiva. Con esta información, se calcularon índices de gestión que permiten sintetizar el desempeño y comparar organizaciones, complejos productivos y ejes de gestión y microrregiones. Los resultados muestran que el desempeño de la gestión competitiva se relaciona con la antigüedad, la formación de las personas que están a cargo y el tamaño de la empresa. Se pudieron conformar tres conglomerados de MiPyMEs, de acuerdo con las variables estructurantes y desempeños de gestión competitiva. La propuesta permitirá evaluar el desempeño en el tiempo y con otros sectores de la economía internacional, nacional o provincial.The organizations of the agri-food and agro-industrial sector are crucial for the development of Latin American countries, where their management and performance have multiplying socioeconomic impacts in the territories. The objective of this work is to measure and evaluate the competitive management of first transformation agro-industrial SMEs in the province of La Pampa, Argentina. 59 of the 74 agro-industries in the province were interviewed, focusing on 9 axes and 54 competitive management factors. With this information, management indices were calculated that allow synthesizing performance and comparing organizations, production complexes, management axes, and micro-regions. The results show that the performance of competitive management is related to seniority, the training of the people in charge and the size of the company. Three conglomerates of SMES could be formed, according to the structuring variables and competitive management performance. The proposal will allow evaluating performance over time and with other sectors of the international, national or provincial economy.Fil: Perez, Santiago Agustin. Universidad Nacional de La Pampa. Facultad de Agronomía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ferro Moreno, Santiago. Universidad Nacional de La Pampa. Facultad de Agronomía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Dopamine Pathology in Schizophrenia: Analysis of Total and Phosphorylated Tyrosine Hydroxylase in the Substantia Nigra

Introduction: Despite the importance of dopamine neurotransmission in schizophrenia, very few studies have addressed anomalies in the mesencephalic dopaminergic neurons of the substantia nigra/ventral tegmental area (SN/VTA). Tyrosine hydroxylase (TH) is the rate-limiting enzyme for the production of dopamine, and a possible contributor to the anomalies in the dopaminergic neurotransmission observed in schizophrenia. Objectives: In this study, we had three objectives: (1) Compare TH expression (mRNA and protein) in the SN/VTA of schizophrenia and control postmortem samples. (2) Assess the effect of antipsychotic medications on the expression of TH in the SN/VTA. (3) Examine possible regional differences in TH expression anomalies within the SN/VTA. Methods: To achieve these objectives three independent studies were conducted: (1) A pilot study to compare TH mRNA and TH protein levels in the SN/VTA of postmortem samples from schizophrenia and controls. (2) A chronic treatment study was performed in rodents to assess the effect of antipsychotic medications in TH protein levels in the SN/VTA. (3) A second postmortem study was performed to assess TH and phosphorylated TH protein levels in two types of samples: schizophrenia and control samples containing the entire rostro-caudal extent of the SN/VTA, and schizophrenia and control samples containing only mid-caudal regions of the SN/VTA. Results and Conclusion: Our studies showed impairment in the dopaminergic system in schizophrenia that could be mainly (or exclusively) located in the rostral region of the SN/VTA. Our studies also showed that TH protein levels were significantly abnormal in schizophrenia, while mRNA expression levels were not affected, indicating that TH pathology in this region may occur posttranscriptionally. Lastly, our antipsychotic animal treatment study showed that TH protein levels were not significantly affected by antipsychotic treatment, indicating that these anomalies are an intrinsic pathology rather than a treatment effect

Brief report: Responses to rituximab suggest B cell-independent inflammation in cutaneous systemic lupus erythematosus

Objective The immunopathogenesis of systemic lupus erythematosus (SLE) is heterogeneous, and responses of skin to rituximab are variable. This study was undertaken to determine the phenotype of rituximab-responsive disease. Methods Eighty-two patients with SLE who were receiving rituximab were prospectively studied. Of these patients, 32 had significant skin involvement before or after treatment. Disease activity was assessed using the British Isles Lupus Assessment Group (BILAG) index 2004. Cutaneous lupus subtype was classified by a dermatologist as acute cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE), chronic cutaneous lupus erythematosus (CCLE), or other skin diseases, with supportive photographs or biopsies where necessary. Results Of 26 patients with skin disease at baseline, 9 (35%) had a beneficial mucocutaneous response to rituximab at 6 months, with good responses in ACLE (6 of 14 patients [43%]), and poor responses in CCLE (0 of 8 patients) (P=0.034). Clinical response was associated with anti-RNP negativity (P=0.024) and anti-Ro negativity (P=0.031). Flares of SCLE and CCLE occurred in 12 patients who either had no skin disease or had ACLE at baseline (i.e., a switch in subtype). Concomitant antimalarials or conventional immunosuppressants were not associated with response or flare rate. Posttreatment biopsies confirmed typical active SLE histology in lesions occurring during B cell depletion. Conclusion Our findings indicate that the clinical response to rituximab in cutaneous manifestations of SLE depends on subtype. None of the CCLE patients responded, and new CCLE lesions were observed during B cell depletion, suggesting that initiation and activity of these lesions is not B cell dependent. Flares of a range of skin diseases after B cell depletion may indicate a change in immune regulation following B cell-targeted therapy

Avaliação de estratégias na pecuária: aplicação do framework de opções reais

El modelo productivo de ganadería bovina de carne se caracteriza por ser un proceso de etapas secuenciales hasta lograr el animal terminado. En la actualidad, la valuación de decisiones bajo contextos propios de la actividad es lineal y estático. En el presente trabajo se analiza y valúa un modelo de decisión de producción y comercial, considerando riesgos de mercado, riesgos tecnológicos y valores de flexibilidad de estrategias posibles para llegar a la fase final del proceso productivo. Se propone un modelo multinomial empleando opciones reales exóticas del tipo arco iris. Se realiza el desarrollo de un árbol de decisión que permita describir la operación, al igual que el planteo matemático y su debida valuación. Se utilizaron modelos reales en casos de ganadería de región pampeana a valores de marzo del año 2022. Como resultados se puede extraer que decisión a tomar considerando un solo escenario, y con la comparación con las estrategias según escenarios positivos y negativos de la actividad. Se puede concluir con la potencialidad, simplicidad y ventajas que permite el desarrollo y aplicación de un modelo de opciones reales, valorando la flexibilidad estratégica de las decisiones, aplicado al complejo ganadero.The beef cattle production model is characterized by being a process of sequential stages until the finished animal is achieved. At present, the valuation of decisions under contexts typical of the activity is linear and static. In the present work, a production and commercial decision model is analyzed and evaluated, considering market risks, technological risks and flexibility values of possible strategies to reach the final phase of the production process. A multinomial model is proposed using exotic real options of the rainbow type. The development of a decision tree that allows describing the operation is carried out, as well as the mathematical approach and its due valuation. Real models were used in cases of livestock in the Pampas region at values of March 2022. As results, it can be extracted what decision to make considering a single scenario, and with the comparison with the strategies according to positive and negative scenarios of the activity. It can be concluded with the potential, simplicity and advantages that the development and application of a real options model allows, valuing the strategic flexibility of the decisions, applied to the livestock complex.O modelo de produção de gado de corte caracteriza-se por ser um processo de etapas sequenciais até a obtenção do animal terminado. Atualmente, a valoração das decisões em contextos típicos da atividade é linear e estática. No presente trabalho é analisado e avaliado um modelo de decisão de produção e comercial, considerando riscos de mercado, riscos tecnológicos e valores de flexibilidade de estratégias possíveis para chegar à fase final do processo produtivo. Um modelo multinomial é proposto usando opções reais exóticas do tipo arco-íris. É realizado o desenvolvimento de uma árvore de decisão que permite descrever a operação, bem como a abordagem matemática e a sua devida avaliação. Foram utilizados modelos reais em casos de pecuária na região dos Pampas em valores de março de 2022. Como resultados, pode-se extrair qual decisão tomar considerando um único cenário, e com a comparação com as estratégias de acordo com cenários positivos e negativos de a atividade. Pode-se concluir com o potencial, simplicidade e vantagens que o desenvolvimento e aplicação de um modelo de opções reais permite, valorizando a flexibilidade estratégica das decisões, aplicadas ao complexo pecuário.Fil: Perez, Santiago Agustin. Universidad Nacional de La Pampa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Confluencia; ArgentinaFil: Ferro Moreno, Santiago. Universidad Nacional de La Pampa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Confluencia; ArgentinaFil: Milanesi, Gastón. Universidad Nacional del Sur. Departamento de Ciencias de la Administración; Argentin

Light and Electron Microscopy Study of Glycogen Synthase Kinase-3β in the Mouse Brain

Glycogen synthase kinase-3β (GSK3β) is highly abundant in the brain. Various biochemical analyses have indicated that GSK3β is localized to different intracellular compartments within brain cells. However, ultrastructural visualization of this kinase in various brain regions and in different brain cell types has not been reported. The goal of the present study was to examine GSK3β distribution and subcellular localization in the brain using immunohistochemistry combined with light and electron microscopy. Initial examination by light microscopy revealed that GSK3β is expressed in brain neurons and their dendrites throughout all the rostrocaudal extent of the adult mouse brain, and abundant GSK3β staining was found in the cortex, hippocampus, basal ganglia, the cerebellum, and some brainstem nuclei. Examination by transmission electron microscopy revealed highly specific subcellular localization of GSK3β in neurons and astrocytes. At the subcellular level, GSK3β was present in the rough endoplasmic reticulum, free ribosomes, and mitochondria of neurons and astrocytes. In addition GSK3β was also present in dendrites and dendritic spines, with some postsynaptic densities clearly labeled for GSK3β. Phosphorylation at serine-9 of GSK3β (pSer9GSK3β) reduces kinase activity. pSer9GSK3β labeling was present in all brain regions, but the pattern of staining was clearly different, with an abundance of labeling in microglia cells in all regions analyzed and much less neuronal staining in the subcortical regions. At the subcellular level pSer9GSK3β labeling was located in the endoplasmic reticulum, free ribosomes and in some of the nuclei. Overall, in normal brains constitutively active GSK3β is predominantly present in neurons while pSer9GSK3β is more evident in resting microglia cells. This visual assessment of GSK3β localization within the subcellular structures of various brain cells may help in understanding the diverse role of GSK3β signaling in the brain

Modelización de articulaciones en el entramado ganadero bovino: aplicación del marco de Teoría de Juegos.

The game theory framework can be used in a wide range of disciplines and case studies. The present work proposes the game theory approach and binomial grids, as strategic tools to analyze and evaluate the articulation and decision making of actors of the bovine livestock complex, specifically breeding and wintering. The originality arises from incorporating the strategic interdependence and articulations between players considering different scenarios of each particular business. The results allow us to conclude that a prisoner's dilemma is reached from the differences between articulating through raised channels. The breeder, as an actor with less power, is the one who should guide greater efforts of direct articulation with the winterer.El marco de teoría de juegos puede ser empleada en un amplio abanico de disciplinas y casos de estudio. El presente trabajo propone el enfoque de teoría de juegos y rejillas binomiales, como herramientas estratégicas para analizar y evaluar la articulación y toma de decisiones de actores del complejo ganadero cárnico bovino, específicamente entre cría e invernada. La originalidad surge de incorporar la interdependencia estratégica y articulaciones entre jugadores considerando distintos escenarios de cada negocio particular. Los resultados permiten concluir que se llega a un dilema de prisionero a partir de las diferencias entre articularse mediante canales planteados. El criador, como actor de menor poder, es quien debería orientar mayores esfuerzos de articulación directa con invernador

Desafíos y oportunidades del agro argentino a 2030

El sector agropecuario argentino enfrenta el reto de producir más alimentos para una población en crecimiento continuo, conservando los recursos naturales y promoviendo la accesibilidad y equidad. En este marco, surgen diversos desafíos y oportunidades territoriales, sectoriales y empresariales. Conocer la opinión de expertos y actores clave del entramado agropecuario es relevante. Mediante un formulario online se obtuvo las perspectivas de 129 actores de diversos subsectores del entramado: agropecuario, agroindustrial, gobierno provincial, académico y profesional. Se destacan aspectos de tecnología, ambientales y políticos como variables de incidencia clave para el futuro del sector.Fil: Perez, Santiago Agustin. Universidad Nacional de La Pampa. Facultad de Agronomía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Confluencia; ArgentinaFil: Gonzalez, Rocio Lujan. Universidad Nacional de La Pampa. Facultad de Agronomía; ArgentinaFil: Ferro Moreno, Santiago. Universidad Nacional de La Pampa. Facultad de Agronomía; Argentin