Activation of heat shock and antioxidant responses by the natural product celastrol: transcriptional signatures of a thiol-targeted molecule.

Stress response pathways allow cells to sense and respond to environmental changes and adverse pathophysiological states. Pharmacological modulation of cellular stress pathways has implications in the treatment of human diseases, including neurodegenerative disorders, cardiovascular disease, and cancer. The quinone methide triterpene celastrol, derived from a traditional Chinese medicinal herb, has numerous pharmacological properties, and it is a potent activator of the mammalian heat shock transcription factor HSF1. However, its mode of action and spectrum of cellular targets are poorly understood. We show here that celastrol activates Hsf1 in Saccharomyces cerevisiae at a similar effective concentration seen in mammalian cells. Transcriptional profiling revealed that celastrol treatment induces a battery of oxidant defense genes in addition to heat shock genes. Celastrol activated the yeast Yap1 oxidant defense transcription factor via the carboxy-terminal redox center that responds to electrophilic compounds. Antioxidant response genes were likewise induced in mammalian cells, demonstrating that the activation of two major cell stress pathways by celastrol is conserved. We report that celastrol's biological effects, including inhibition of glucocorticoid receptor activity, can be blocked by the addition of excess free thiol, suggesting a chemical mechanism for biological activity based on modification of key reactive thiols by this natural product.

Dispersive analysis of the pion transition form factor

We analyze the pion transition form factor using dispersion theory. We calculate the singly-virtual form factor in the time-like region based on data for the e+e−→3π cross section, generalizing previous studies on ω,ϕ→3π decays and γπ→ππ scattering, and verify our result by comparing to e+e−→π0γ data. We perform the analytic continuation to the space-like region, predicting the poorly-constrained space-like transition form factor below 1GeV, and extract the slope of the form factor at vanishing momentum transfer aπ=(30.7±0.6)×10−3. We derive the dispersive formalism necessary for the extension of these results to the doubly-virtual case, as required for the pion-pole contribution to hadronic light-by-light scattering in the anomalous magnetic moment of the muon.

A practical approach to designing syndromic surveillance systems for livestock and poultry

The field of animal syndromic surveillance (SyS) is growing, with many systems being developed worldwide. Now is an appropriate time to share ideas and lessons learned from early SyS design and implementation. Based on our practical experience in animal health SyS, with additions from the public health and animal health SyS literature, we put forward for discussion a 6-step approach to designing SyS systems for livestock and poultry. The first step is to formalise policy and surveillance goals which are considerate of stakeholder expectations and reflect priority issues (1). Next, it is important to find consensus on national priority diseases and identify current surveillance gaps. The geographic, demographic, and temporal coverage of the system must be carefully assessed (2). A minimum dataset for SyS that includes the essential data to achieve all surveillance objectives while minimizing the amount of data collected should be defined. One can then compile an inventory of the data sources available and evaluate each using the criteria developed (3). A list of syndromes should then be produced for all data sources. Cases can be classified into syndrome classes and the data can be converted into time series (4). Based on the characteristics of the syndrome-time series, the length of historic data available and the type of outbreaks the system must detect, different aberration detection algorithms can be tested (5). Finally, it is essential to develop a minimally acceptable response protocol for each statistical signal produced (6). Important outcomes of this pre-operational phase should be building of a national network of experts and collective action and evaluation plans. While some of the more applied steps (4 and 5) are currently receiving consideration, more emphasis should be put on earlier conceptual steps by decision makers and surveillance developers (1-3).

Partitioning the Choice Task Makes Starbucks Coffee Taste Better

Consumers are often less satisfied with a product chosen from a large assortment than a limited one. Experienced choice difficulty presumably causes this as consumers have to engage in a great number of individual comparisons. In two studies we tested whether partitioning the choice task so that consumers decided sequentially on each individual attribute may provide a solution. In a Starbucks coffee house, consumers who chose from the menu rated the coffee as less tasty when chosen from a large rather than a small assortment. However, when the consumers chose it by sequentially deciding about one attribute at a time, the effect reversed. In a tailored-suit customization, consumers who chose multiple attributes at a time were less satisfied with their suit, compared to those who chose one attribute at a time. Sequential attribute-based processing proves to be an effective strategy to reap the benefits of a large assortment.

Towards the identification of a tumor suppressor gene on chromosome 3p12: Physical mapping and candidate gene screening

Renal cell carcinoma (RCC) is the most common malignant tumor of the kidney. Characterization of RCC tumors indicates that the most frequent genetic event associated with the initiation of tumor formation involves a loss of heterozygosity or cytogenetic aberration on the short arm of human chromosome 3. A tumor suppressor locus Nonpapillary Renal Carcinoma-1 (NRC-1, OMIM ID 604442) has been previously mapped to a 5–7 cM region on chromosome 3p12 and shown to induce rapid tumor cell death in vivo, as demonstrated by functional complementation experiments. ^ To identify the gene that accounts for the tumor suppressor activities of NRC-1, fine-scale physical mapping was conducted with a novel real-time quantitative PCR based method developed in this study. As a result, NRC-1 was mapped within a 4.6-Mb region defined by two unique sequences within UniGene clusters Hs.41407 and Hs.371835 (78,545Kb–83,172Kb in the NCBI build 31 physical map). The involvement of a putative tumor suppressor gene Robo1/Dutt1 was excluded as a candidate for NRC-1. Furthermore, a transcript map containing eleven candidate genes was established for the 4.6-Mb region. Analyses of gene expression patterns with real-time quantitative RT-PCR assays showed that one of the eleven candidate genes in the interval (TSGc28) is down-regulated in 15 out of 20 tumor samples compared with matched normal samples. Three exons of this gene have been identified by RACE experiments, although additional exon(s) seem to exist. Further gene characterization and functional studies are required to confirm the gene as a true tumor suppressor gene. ^ To study the cellular functions of NRC-1, gene expression profiles of three tumor suppressive microcell hybrids, each containing a functional copy of NRC-1, were compared with those of the corresponding parental tumor cell lines using 16K oligonucleotide microarrays. Differentially expressed genes were identified. Analyses based on the Gene Ontology showed that introduction of NRC-1 into tumor cell lines activates genes in multiple cellular pathways, including cell cycle, signal transduction, cytokines and stress response. NRC-1 is likely to induce cell growth arrest indirectly through WEE1. ^

South Asian immigrant cardiovascular risk assessment in Houston, Texas 2005

Background. Heart disease is the leading cause of death and stroke is the third leading cause of deaths for all people in the United States. South Asian Americans have a higher risk of developing cardiovascular diseases than native United States residents. ^ Purpose. This study examines the cardiovascular risk factors in the South Asian immigrant community residing in Southwest Houston. This study also explores the level of health insurance available to the South Asian in Houston. ^ Methods. One hundred sixty-two South Asian patients aged 18 years and older received cardiovascular screening from January 1 st, 2005 to March 31st, 2005 at Ibn Sina Community Clinic; blood pressure was measured twice in both arms after resting five minutes. Height and weight were also recorded. Demographic data was collected through personal interview (questionnaire) and blood samples were drawn to collect laboratory data. ^ Results. There were 162 eligible South Asian patients, among whom 127 (78%) participated in the study. There were no significant differences between the responders and the non-responders in terms of demographics and clinical characteristics. Laboratory data revealed a mean total cholesterol of 201 ± 34 mg/dl, 54 percent had high total cholesterol above 200 mg/dl. The mean fasting glucose was 108 ± 43 mg/dl, and body mass index (BMI) was 28 ± 4 kg/m2. The prevalence of hypertension was comparable with the general U.S. population; 38 percent of the South Asian males and 29 percent of females had hypertension. The prevalence of diabetes was also compared; 21 percent of SA males (3% for white American males) and 7 percent of SA females (2% for white American females) were found to have undiagnosed diabetes. Of the sample 12 percent had both hypertension and diabetes; 21 percent had both hypertension and high BMI, and 19 percent had hypertension and high total cholesterol levels. ^ Conclusion. The present study shows that the South Asians in this sample are at greater risk of developing cardiovascular diseases than other ethnicities. The high prevalence of hypertension, type 2 diabetes, higher total cholesterol levels with overweight and obesity, and less leisure time physical activity are important cardiovascular risk factors for South Asians population. ^

The economic cost of type 2 diabetes attributable to physical inactivity in the United States and Texas in 2007

Type 2 diabetes has grown to epidemic proportions in the U.S., and its prevalence has been steadily increasing in Texas. The physical activity levels in the population have remained low despite it being one of the primary preventive strategies for type 2 diabetes. The objectives of this study were to estimate the direct medical costs of type 2 diabetes attributable to not meeting physical activity Guidelines and to physical inactivity in the U.S. and Texas in 2007. This was a cross sectional study that used physical activity prevalence data from the 2007 Behavioral Risk Factor Surveillance System (BRFSS) to estimate the population attributable risk percentage (PAR%) for type 2 diabetes. These data were combined with the prevalence and cost data of type 2 diabetes to estimate the cost of type 2 diabetes attributable to not meeting Guidelines and to inactivity in the U.S. and Texas in 2007.^ The cost of type 2 diabetes in the U.S. in 2007, attributable to not meeting physical activity Guidelines was estimated to be $13.29 billion, and that attributable to physical inactivity (no leisure time physical activity) was estimated to be $3.32 billion. Depending on various assumptions, these estimates ranged from $7.61 billion to $41.48 billion for not meeting Guidelines, and $1.90 billion to $13.20 billion for physical inactivity in the U.S. in 2007. The cost of type 2 diabetes in Texas in 2007 attributable to not meeting physical activity Guidelines was estimated to be $1.15 billion, and that attributable to physical inactivity (no leisure time physical activity) was estimated to be $325 million. Depending on various assumptions, these estimates ranged from $800 million to $3.47 billion for not meeting Guidelines, and $186 million to $1.28 billion for physical inactivity in Texas in 2007. These results illustrate how much money could be saved annually just in terms of type 2 diabetes cost in the U.S. and Texas, if the entire adult population was active enough to meet physical activity Guidelines. Physical activity promotion, particularly at the environmental and policy level should be a priority in the population. ^

Plio-Pleistocene diatom biostratigraphy from ODP Leg 177, Atlantic sector of the Southern Ocean

Seven sites were drilled during Ocean Drilling Program Leg 177 in the Atlantic sector of the Southern Ocean (SO) on a transect over the Antarctic Circumpolar Current from the Subantarctic to the Antarctic Zone. At four sites sediments were recovered with a Pliocene/Pleistocene sediment package of up to 580 m allowing the refinement of previous diatom zonation concepts. Samples were analyzed on stratigraphic distribution and abundance of diatom species. A refined diatom biozonation tied to the geomagnetic polarity record is proposed. For the middle and late Pleistocene two zonations applicable to the northern and southern area of the SO were constructed, considering different latitudinal distributions of biostratigraphic diatom marker species. The southern zonation for the Pleistocene relies on the occurrence of species of the genus Rouxia, R. leventerae and R. constricta n. sp. as well as on a revised last occurrence datum (LOD) of Actinocyclus ingens (0.38 Ma, late marine isotope stage (MIS) 11). The use of these new stratigraphic marker species refines the temporal resolution for biostratigraphic age assignment to up to 0.1 Myr. In particular the LOD of R. leventerae as an indicator for the MIS 6/5 boundary (Termination II) will improve future dating of carbonate-free Antarctic sediments. These new data were obtained from sediments of Sites 1093 and 1094 (Antarctic Zone). The northern zonation for the middle and late Pleistocene time interval is based on the Pleistocene abundance pattern of Hemidiscus karstenii which was already proposed by previous investigations (e.g. Gersonde and Barcena, 1998). One new species (R. constricta) and two new combinations (Fragilariopsis clementia, Fragilariopsis reinholdii) are proposed in this study.

Pollen records and age determinations from 2 profiles at Lake Nikolay, Lena Delta

Radiocarbon-dated pollen, rhizopod, chironomid and total organic carbon (TOC) records from Nikolay Lake (73°20'N, 124°12'E) and a pollen record from a nearby peat sequence are used for a detailed environmental reconstruction of the Holocene in the Lena Delta area. Shrubby Alnus fruticosa and Betula exilis tundra existed during 10,300-4800 cal. yr BP and gradually disappeared after that time. Climate reconstructions based on the pollen and chironomid records suggest that the climate during ca. 10,300-9200 cal. yr BP was up to 2-3 °C warmer than the present day. Pollen-based reconstructions show that the climate was relatively warm during 9200-6000 cal. yr BP and rather unstable between ca. 5800-3700 cal. yr BP. Both the qualitative interpretation of pollen data and the results of quantitative reconstruction indicate that climate and vegetation became similar to modern-day conditions after ca. 3600 cal. yr BP. The chironomid-based temperature reconstruction suggests a relatively warm period between ca. 2300 and 1400 cal. yr BP, which corresponds to the slightly warmer climate conditions reconstructed from the pollen. Modern chironomid and rhizopod assemblages were established after ca. 1400 cal. yr BP.

Oxygen isotopes, IRD and SST reconstruction for the interval MIS31-19 of IODP Site 306-U1314

Early and Mid-Pleistocene climate, ocean hydrography and ice sheet dynamics have been reconstructed using a high-resolution data set (planktonic and benthic d18O time series, faunal-based sea surface temperature (SST) reconstructions and ice-rafted debris (IRD)) record from a high-deposition-rate sedimentary succession recovered at the Gardar Drift formation in the subpolar North Atlantic (Integrated Ocean Drilling Program Leg 306, Site U1314). Our sedimentary record spans from late in Marine Isotope Stage (MIS) 31 to MIS 19 (1069-779 ka). Different trends of the benthic and planktonic oxygen isotopes, SST and IRD records before and after MIS 25 (~940 ka) evidence the large increase in Northern Hemisphere ice-volume, linked to the cyclicity change from the 41-kyr to the 100-kyr that occurred during the Mid-Pleistocene Transition (MPT). Beside longer glacial-interglacial (G-IG) variability, millennial-scale fluctuations were a pervasive feature across our study. Negative excursions in the benthic d18O time series observed at the times of IRD events may be related to glacio-eustatic changes due to ice sheets retreats and/or to changes in deep hydrography. Time series analysis on surface water proxies (IRD, SST and planktonic d18O) of the interval between MIS 31 to MIS 26 shows that the timing of these millennial-scale climate changes are related to half-precessional (10 kyr) components of the insolation forcing, which are interpreted as cross-equatorial heat transport toward high latitudes during both equinox insolation maxima at the equator.

Cultura, identidad y territorio : Reflexiones para el desarrollo de una estrategia de diferenciación del servicio agroturístico en emprendimientos de un Grupo de Cambio Rural (INTA) del partido de Coronel Suárez (Buenos Aires)

A partir de los conceptos convergentes identidad, cultura, patrimonio y territorio, se plantea analizar la posibilidad de formular e implementar una estrategia de diferenciación para la actividad de agroturismo desarrollada por los establecimientos del grupo Cortaderas II (Cambio Rural, INTA), en el partido de Coronel Suárez (BA), provincia de Buenos Aires. Con este fin, se ha efectuado un diagnóstico mediante entrevistas directas y observaciones in situ de los emprendimientos participantes. Destacando aspectos propios de su ambiente rural, se procuró identificar valores culturales y productos con anclaje territorial que impongan un sello distintivo al servicio turístico que ofrecen. Complementariamente, se indagó en qué medida los integrantes están preparados para gestionar el negocio, reconociendo en ellos competencias gerenciales y características emprendedoras. Por último, se reflexiona acerca del grado de madurez alcanzado, tipificando la cultura empresarial individual y según el trabajo grupal, de modo de evaluar si la puesta en valor de sus recursos evoluciona desde un "carácter doméstico" hasta llegar a un "carácter comercial formal". Se observa la construcción de una identidad de índole socio-cultural-económica que hace viable una estrategia competitiva diferencial con anclaje en el territorio, así como condiciones para el desarrollo de una actividad turística más formalizada basada en la gestión de calidad

Medio ambiente social y cultural : Análisis de los enunciados de las clases de Educación Física

El análisis de las acciones verbales que tienen lugar en las clases proporciona información sobre las prácticas docentes. Los seres humanos contamos con el lenguaje como herramienta fundamental para comunicarnos y construir conocimiento. La reflexión sobre su uso, concretamente el uso que los docentes hacen de este instrumento netamente humano en sus prácticas, es esencial para acrecentar nuestro conocimiento acerca de la tarea docente.
Desde el área de la Didáctica de la Lengua y los enfoques teóricos de la Teoría de la actividad (Leontiev, 1983) y el Interaccionismo socio-discursivo (Bronckart, 1997/2004, 2007), emprendemos este trabajo que se circunscribe al material resultado de las observaciones de clases de Educación Física de nivel primario de escuelas públicas de San Carlos de Bariloche (Río Negro-Argentina). La metodología consiste en convertir los textos orales de las clases en registros escritos para estudiar su organización interna según tres niveles superpuestos, tal como Bronckart (1997/2004) plantea. El resultado es un trabajo de corte cualitativo en el que se estudian en profundidad los contenidos actitudinales presentes en las clases.
Nuestro objetivo es estudiar las interacciones docente-alumnos en el medio social áulico para determinar a través de qué actividades los docentes propiciamos el desarrollo de nuestros alumnos. Es decir, analizar cómo a través de los enunciados de los docentes, se construye el medio ambiente social y cultural (Voloshinov, 1992; Riestra, 2011) en las clases de Educación física.

Cultura, identidad y territorio : Reflexiones para el desarrollo de una estrategia de diferenciación del servicio agroturístico en emprendimientos de un Grupo de Cambio Rural (INTA) del partido de Coronel Suárez (Buenos Aires)

A partir de los conceptos convergentes identidad, cultura, patrimonio y territorio, se plantea analizar la posibilidad de formular e implementar una estrategia de diferenciación para la actividad de agroturismo desarrollada por los establecimientos del grupo Cortaderas II (Cambio Rural, INTA), en el partido de Coronel Suárez (BA), provincia de Buenos Aires. Con este fin, se ha efectuado un diagnóstico mediante entrevistas directas y observaciones in situ de los emprendimientos participantes. Destacando aspectos propios de su ambiente rural, se procuró identificar valores culturales y productos con anclaje territorial que impongan un sello distintivo al servicio turístico que ofrecen. Complementariamente, se indagó en qué medida los integrantes están preparados para gestionar el negocio, reconociendo en ellos competencias gerenciales y características emprendedoras. Por último, se reflexiona acerca del grado de madurez alcanzado, tipificando la cultura empresarial individual y según el trabajo grupal, de modo de evaluar si la puesta en valor de sus recursos evoluciona desde un "carácter doméstico" hasta llegar a un "carácter comercial formal". Se observa la construcción de una identidad de índole socio-cultural-económica que hace viable una estrategia competitiva diferencial con anclaje en el territorio, así como condiciones para el desarrollo de una actividad turística más formalizada basada en la gestión de calidad

Medio ambiente social y cultural : Análisis de los enunciados de las clases de Educación Física

El análisis de las acciones verbales que tienen lugar en las clases proporciona información sobre las prácticas docentes. Los seres humanos contamos con el lenguaje como herramienta fundamental para comunicarnos y construir conocimiento. La reflexión sobre su uso, concretamente el uso que los docentes hacen de este instrumento netamente humano en sus prácticas, es esencial para acrecentar nuestro conocimiento acerca de la tarea docente.
Desde el área de la Didáctica de la Lengua y los enfoques teóricos de la Teoría de la actividad (Leontiev, 1983) y el Interaccionismo socio-discursivo (Bronckart, 1997/2004, 2007), emprendemos este trabajo que se circunscribe al material resultado de las observaciones de clases de Educación Física de nivel primario de escuelas públicas de San Carlos de Bariloche (Río Negro-Argentina). La metodología consiste en convertir los textos orales de las clases en registros escritos para estudiar su organización interna según tres niveles superpuestos, tal como Bronckart (1997/2004) plantea. El resultado es un trabajo de corte cualitativo en el que se estudian en profundidad los contenidos actitudinales presentes en las clases.
Nuestro objetivo es estudiar las interacciones docente-alumnos en el medio social áulico para determinar a través de qué actividades los docentes propiciamos el desarrollo de nuestros alumnos. Es decir, analizar cómo a través de los enunciados de los docentes, se construye el medio ambiente social y cultural (Voloshinov, 1992; Riestra, 2011) en las clases de Educación física.

Cultura, identidad y territorio : Reflexiones para el desarrollo de una estrategia de diferenciación del servicio agroturístico en emprendimientos de un Grupo de Cambio Rural (INTA) del partido de Coronel Suárez (Buenos Aires)

A partir de los conceptos convergentes identidad, cultura, patrimonio y territorio, se plantea analizar la posibilidad de formular e implementar una estrategia de diferenciación para la actividad de agroturismo desarrollada por los establecimientos del grupo Cortaderas II (Cambio Rural, INTA), en el partido de Coronel Suárez (BA), provincia de Buenos Aires. Con este fin, se ha efectuado un diagnóstico mediante entrevistas directas y observaciones in situ de los emprendimientos participantes. Destacando aspectos propios de su ambiente rural, se procuró identificar valores culturales y productos con anclaje territorial que impongan un sello distintivo al servicio turístico que ofrecen. Complementariamente, se indagó en qué medida los integrantes están preparados para gestionar el negocio, reconociendo en ellos competencias gerenciales y características emprendedoras. Por último, se reflexiona acerca del grado de madurez alcanzado, tipificando la cultura empresarial individual y según el trabajo grupal, de modo de evaluar si la puesta en valor de sus recursos evoluciona desde un "carácter doméstico" hasta llegar a un "carácter comercial formal". Se observa la construcción de una identidad de índole socio-cultural-económica que hace viable una estrategia competitiva diferencial con anclaje en el territorio, así como condiciones para el desarrollo de una actividad turística más formalizada basada en la gestión de calidad