The liver kinase B1 is a central regulator of T cell development, activation, and metabolism.

T cell activation leads to engagement of cellular metabolic pathways necessary to support cell proliferation and function. However, our understanding of the signal transduction pathways that regulate metabolism and their impact on T cell function remains limited. The liver kinase B1 (LKB1) is a serine/threonine kinase that links cellular metabolism with cell growth and proliferation. In this study, we demonstrate that LKB1 is a critical regulator of T cell development, viability, activation, and metabolism. T cell-specific ablation of the gene that encodes LKB1 resulted in blocked thymocyte development and a reduction in peripheral T cells. LKB1-deficient T cells exhibited defects in cell proliferation and viability and altered glycolytic and lipid metabolism. Interestingly, loss of LKB1 promoted increased T cell activation and inflammatory cytokine production by both CD4(+) and CD8(+) T cells. Activation of the AMP-activated protein kinase (AMPK) was decreased in LKB1-deficient T cells. AMPK was found to mediate a subset of LKB1 functions in T lymphocytes, as mice lacking the α1 subunit of AMPK displayed similar defects in T cell activation, metabolism, and inflammatory cytokine production, but normal T cell development and peripheral T cell homeostasis. LKB1- and AMPKα1-deficient T cells each displayed elevated mammalian target of rapamycin complex 1 signaling and IFN-γ production that could be reversed by rapamycin treatment. Our data highlight a central role for LKB1 in T cell activation, viability, and metabolism and suggest that LKB1-AMPK signaling negatively regulates T cell effector function through regulation of mammalian target of rapamycin activity.

Selected Gamma Aminobutyric Acid (GABA) Esters may Provide Analgesia for Some Central Pain Conditions.

Central pain is an enigmatic, intractable condition, related to destruction of thalamic areas, resulting in likely loss of inhibitory synaptic transmission mediated by GABA. It is proposed that treatment of central pain, a localized process, may be treated by GABA supplementation, like Parkinson's disease and depression. At physiologic pH, GABA exists as a zwitterion that is poorly permeable to the blood brain barrier (BBB). Because the pH of the cerebral spinal fluid (CSF) is acidic relative to the plasma, ion trapping may allow a GABA ester prodrug to accumulate and be hydrolyzed within the CSF. Previous investigations with ester local anesthetics may be applicable to some GABA esters since they are weak bases, hydrolyzed by esterases and cross the BBB. Potential non-toxic GABA esters are discussed. Many GABA esters were investigated in the 1980s and it is hoped that this paper may spark renewed interest in their development.

The Representation of Emotion in Autonomic and Central Nervous System Activity

Phenomenologically, humans effectively label and report feeling distinct emotions, yet the extent to which emotions are represented categorically in nervous system activity is controversial. Theoretical accounts differ in this regard, some positing distinct emotional experiences emerge from a dimensional representation (e.g., along axes of valence and arousal) whereas others propose emotions are natural categories, with dedicated neural bases and associated response profiles. This dissertation aims to empirically assess these theoretical accounts by examining how emotions are represented (either as disjoint categories or as points along continuous dimensions) in autonomic and central nervous system activity by integrating psychophysiological recording and functional neuroimaging with machine-learning based analytical methods. Results demonstrate that experientially, emotional events are well-characterized both along dimensional and categorical frameworks. Measures of central and peripheral responding discriminate among emotion categories, but are largely independent of valence and arousal. These findings suggest dimensional and categorical aspects of emotional experience are driven by separable neural substrates and demonstrate that emotional states can be objectively quantified on the basis of nervous system activity.

ARFGAP1 plays a central role in coupling COPI cargo sorting with vesicle formation.

Examining how key components of coat protein I (COPI) transport participate in cargo sorting, we find that, instead of ADP ribosylation factor 1 (ARF1), its GTPase-activating protein (GAP) plays a direct role in promoting the binding of cargo proteins by coatomer (the core COPI complex). Activated ARF1 binds selectively to SNARE cargo proteins, with this binding likely to represent at least a mechanism by which activated ARF1 is stabilized on Golgi membrane to propagate its effector functions. We also find that the GAP catalytic activity plays a critical role in the formation of COPI vesicles from Golgi membrane, in contrast to the prevailing view that this activity antagonizes vesicle formation. Together, these findings indicate that GAP plays a central role in coupling cargo sorting and vesicle formation, with implications for simplifying models to describe how these two processes are coupled during COPI transport.

Dust in the wind: How climate variables and volcanic dust affect rates of tooth wear in Central American howling monkeys.

OBJECTIVES: Two factors have been considered important contributors to tooth wear: dietary abrasives in plant foods themselves and mineral particles adhering to ingested food. Each factor limits the functional life of teeth. Cross-population studies of wear rates in a single species living in different habitats may point to the relative contributions of each factor. MATERIALS AND METHODS: We examine macroscopic dental wear in populations of Alouatta palliata (Gray, 1849) from Costa Rica (115 specimens), Panama (19), and Nicaragua (56). The sites differ in mean annual precipitation, with the Panamanian sites receiving more than twice the precipitation of those in Costa Rica or Nicaragua (∼3,500 mm vs. ∼1,500 mm). Additionally, many of the Nicaraguan specimens were collected downwind of active plinian volcanoes. Molar wear is expressed as the ratio of exposed dentin area to tooth area; premolar wear was scored using a ranking system. RESULTS: Despite substantial variation in environmental variables and the added presence of ash in some environments, molar wear rates do not differ significantly among the populations. Premolar wear, however, is greater in individuals collected downwind from active volcanoes compared with those living in environments that did not experience ash-fall. DISCUSSION: Volcanic ash seems to be an important contributor to anterior tooth wear but less so in molar wear. That wear is not found uniformly across the tooth row may be related to malformation in the premolars due to fluorosis. A surge of fluoride accompanying the volcanic ash may differentially affect the premolars as the molars fully mineralize early in the life of Alouatta.

Physical Activity, Central Adiposity, and Functional Limitations in Community-Dwelling Older Adults.

BACKGROUND AND PURPOSE: Obesity and physical inactivity are independently associated with physical and functional limitations in older adults. The current study examines the impact of physical activity on odds of physical and functional limitations in older adults with central and general obesity. METHODS: Data from 6279 community-dwelling adults aged 60 years or more from the Health and Retirement Study 2006 and 2008 waves were used to calculate prevalence and odds of physical and functional limitation among obese older adults with high waist circumference (waist circumference ≥88 cm in females and ≥102 cm in males) who were physically active versus inactive (engaging in moderate/vigorous activity less than once per week). Logistic regression models were adjusted for age, sex, race/ethnicity, education, smoking status, body mass index, and number of comorbidities. RESULTS: Physical activity was associated with lower odds of physical and functional limitations among older adults with high waist circumference (odds ratio [OR], 0.59; confidence interval [CI], 0.52-0.68, for physical limitations; OR, 0.52; CI, 0.44-0.62, for activities of daily living; and OR, 0.44; CI, 0.39-0.50, for instrumental activities of daily living). CONCLUSIONS: Physical activity is associated with significantly lower odds of physical and functional limitations in obese older adults regardless of how obesity is classified. Additional research is needed to determine whether physical activity moderates long-term physical and functional limitations.

Live Imaging of Host-Parasite Interactions in a Zebrafish Infection Model Reveals Cryptococcal Determinants of Virulence and Central Nervous System Invasion.

UNLABELLED: The human fungal pathogen Cryptococcus neoformans is capable of infecting a broad range of hosts, from invertebrates like amoebas and nematodes to standard vertebrate models such as mice and rabbits. Here we have taken advantage of a zebrafish model to investigate host-pathogen interactions of Cryptococcus with the zebrafish innate immune system, which shares a highly conserved framework with that of mammals. Through live-imaging observations and genetic knockdown, we establish that macrophages are the primary immune cells responsible for responding to and containing acute cryptococcal infections. By interrogating survival and cryptococcal burden following infection with a panel of Cryptococcus mutants, we find that virulence factors initially identified as important in causing disease in mice are also necessary for pathogenesis in zebrafish larvae. Live imaging of the cranial blood vessels of infected larvae reveals that C. neoformans is able to penetrate the zebrafish brain following intravenous infection. By studying a C. neoformans FNX1 gene mutant, we find that blood-brain barrier invasion is dependent on a known cryptococcal invasion-promoting pathway previously identified in a murine model of central nervous system invasion. The zebrafish-C. neoformans platform provides a visually and genetically accessible vertebrate model system for cryptococcal pathogenesis with many of the advantages of small invertebrates. This model is well suited for higher-throughput screening of mutants, mechanistic dissection of cryptococcal pathogenesis in live animals, and use in the evaluation of therapeutic agents. IMPORTANCE: Cryptococcus neoformans is an important opportunistic pathogen that is estimated to be responsible for more than 600,000 deaths worldwide annually. Existing mammalian models of cryptococcal pathogenesis are costly, and the analysis of important pathogenic processes such as meningitis is laborious and remains a challenge to visualize. Conversely, although invertebrate models of cryptococcal infection allow high-throughput assays, they fail to replicate the anatomical complexity found in vertebrates and, specifically, cryptococcal stages of disease. Here we have utilized larval zebrafish as a platform that overcomes many of these limitations. We demonstrate that the pathogenesis of C. neoformans infection in zebrafish involves factors identical to those in mammalian and invertebrate infections. We then utilize the live-imaging capacity of zebrafish larvae to follow the progression of cryptococcal infection in real time and establish a relevant model of the critical central nervous system infection phase of disease in a nonmammalian model.

Adjuvant portal-vein infusion of fluorouracil and heparin in colorectal cancer: A randomised trial

Background. There is conflicting evidence on the efficacy of regional adjuvant chemotherapy, via portal-vein infusion (PVI), after resection of colorectal cancer. We undertook a randomised controlled multicentre trial to investigate the efficacy of PVI (500 mg/m2 fluorouracil plus 5000 IU heparin daily for 7 days). Methods. 1235 of about 1500 potentially eligible patients were randomly assigned surgery plus PVI or surgery alone (control). The patients were followed up for a median of 63 months, with yearly screening for recurrent disease. The primary endpoint was survival; analyses were by intention to treat. Findings. 619 patients in the control group and 616 in the PVI group met eligibility criteria. 164 (26%) control-group patients and 173 (28%) PVI-group patients died. 5-year survival did not differ significantly between the groups (73 vs 72%; 95% CI for difference -6 to 4). The control and PVI groups were also similar in terms of disease-free survival at 5 years (67 vs 65%) and the number of patients with liver metastases (79 vs 77%). Interpretation. PVI of fluorouracil, at a dose of 500 mg/m2 for 7 days, cannot be recommended as the sole adjuvant treatment for high-risk colorectal cancer after complete surgical excision. However, these results cannot eliminate a small benefit when PVI is used at a higher dosage or in combination with mitomycin.

Evaluación de la fenología, el rendimiento y la calidad granométrica de tres variedades de maní (Arachis hypogaea L.), en condiciones de campo para la zona central de Córdoba

El desplazamiento del área de siembra hacia el sur y los requerimientos del mercado obligaron a la introducción de nuevas variedades de maní en reemplazo de las tradicionales. Sin embargo no se han evaluado las tres variedades más difundidas en relación a su comportamiento a campo. El objetivo de este trabajo fue comparar tres variedades comerciales de maní (Arachis hypogaea L.) en términos de fenología, rendimiento y calidad granométrica en condiciones de campo para la zona central de Córdoba. Se llevó a cabo la siembra a campo de las variedades GRANOLEICO, ASEM 484 y ASEM 485. Se evaluaron: a) parámetros fenológicos: emergencia de plántulas, ciclo de las variedades (R1 y R5), estado de madurez de las variedades, b) parámetros productivos: rendimiento (kg/ha) y calidad granométrica, c) análisis económico. De acuerdo a los resultados obtenidos se concluye que la variedad GRANOLEICO requiere mayor tiempo térmico (ºCdía) para cumplir las mismas etapas fenológicas, si bien el rendimiento es similar al obtenido por las variedades ASEM 484 y 485. Sin embargo estas variedades presentan mayor calidad granométrica. La variedad GRANOLEICO obtuvo un (- 16,30 por ciento) y la variedad ASEM 485 un (- 0,46 por ciento) de ingreso ($/ha) respecto de la variedad ASEM 484. Por lo expuesto se sugiere la correcta elección de las variedades de maní, de acuerdo al área y fecha de siembra.

Subsistema estrictamente coordinado de café : central de cooperativas agrarias de la convención y lares 'COCLA'

El café desempeña un papel crucial en la vida de millones de familias campesinas en el mundo en desarrollo. Las pequeñas fincas cafetaleras producen cerca del 75,0 por ciento del café mundial. El sector de café tiene en la agricultura peruana una alta importancia económica y social, generando anualmente 47 millones de jornales. Asimismo el café es la principal fuente de ingresos de 150 mil familias de pequeños agricultores, quienes están ubicados en lugares alejados en la geografía andina y amazónica. Los pequeños productores se sobrepusieron a adversidades políticas y económicas para el modelo asociativo y a largos años de violencia interna en sus zonas. Es así que ante constantes perturbaciones internas debido a la lucha de clases en la década de los sesenta, y perturbaciones externas ligadas al mercado internacional, surge la Central de Cooperativas Agrarias en Cusco 'COCLA'. La estructura organizativa y de gestión que tiene COCLA, permitió realizar cambios en los paradigmas, para rediseñar y adoptar nuevas estrategias entorno al ambiente institucional, organizacional y tecnológico, reflejando la lógica mixta de cooperativa, teniendo su parte asociativa y empresarial, la cadena funciona coordinadamente debido a la acción colectiva. La presente investigación tiene como objetivo principal identificar y describir las fortalezas desde el punto de vista organizacional y las estrategias comerciales en las que se apalancó la inserción del producto de café de la cooperativa COCLA en el mercado externo, para mejorar la inserción de los pequeños productores en el mercado internacional. Se utilizó el tipo de investigación fenomenológica y como metodología de abordaje el estudio de caso simple a la luz de la Nueva Economía Institucional, tomando el caso de la Central de Cooperativas Agrarias en Cusco 'COCLA'. La unidad de análisis estudiada fue el negocio de café de esta organización. El trabajo se desarrolló en base a la recopilación de información secundaria de entidades en el ámbito cafetalero. Adicionalmente se complementó con información primaria tomada de entrevistas realizadas vía telefónica a los representantes de COCLA

La comercialización hortícola : análisis contextual del Mercado Central de Buenos Aires

p.269-278

La brotación y la floración del kiwi en función de las temperaturas invierno - primaverales de la región central de Córdoba

p.183-188

Etnomatemática: eje central de la recuperación de saberes matemáticos. Experiencia de América latina y retos para Costa Rica

El presente artículo recopila la experiencia de expertos en la etnomatemática, de un grupo de discusión en RELME 27. Sus cuestionamientos se fundamentan, en la etnomatemática y el impacto de esta en el currículo escolar. Se toma en cuenta las características sociales del sistema educativo latinoamericano, los objetivos de desarrollo del milenio y el impacto de ambos, sobre la educación matemática de los pueblos originarios. Se plantean retos futuros y una visión sobre la recuperación de los saberes matemáticos. Metodológicamente se sustenta como una investigación de enfoque cualitativo, con diseño de teoría fundamental, donde sus datos se analizan por codificación abierta axial.

Spatial variability of air pollution in the vicinity of a permanent monitoring station in central Paris

The strong spatial and temporal variability of traffic-related air pollution detected at roadside locations in a number of European cities has raised the question of how representative the site and time period of air quality measurements actually can be. To address this question, a 7-month sampling campaign was carried out on a major road axis (Avenue Leclerc) leading to a very busy intersection (Place Basch) in central Paris, covering the surroundings of a permanent air quality monitoring station. This station has recorded the highest CO and NOx concentrations during recent years in the region of Paris. Diffusive BTX samplers as well as a mobile monitoring unit equipped with real-time CO, NOx and O3 analysers and meteorological instruments were used to reveal the small-scale pollution gradients and their temporal trends near the permanent monitoring station. The diffusive measurements provided 7-day averages of benzene, toluene, xylene and other hydrocarbons at different heights above the ground and distances from the kerb covering summer and winter periods. Relevant traffic and meteorological data were also obtained on an hourly basis. Furthermore, three semiempirical dispersion models (STREET-SRI, OSPM and AEOLIUS) were tested for an asymmetric canyon location in Av. Leclerc. The analysis of this comprehensive data set has helped to assess the representativeness of air quality monitoring information.