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101.
Benita Wolf Adrian Schwarzer Anik L. C?té Thomas H. Hampton Thomas Schwaab Eduardo Huarte Craig R. Tomlinson Jiang Gui Jan L. Fisher Camilo E. Fadul Joshua W. Hamilton Marc S. Ernstoff 《PloS one》2012,7(12)
Lymphocytes are a key component of the immune system and their differentiation and function are directly influenced by cancer. We examined peripheral blood lymphocyte (PBL) gene expression as a biomarker of illness and treatment effect using the Affymetrix Human Gene ST1 platform in patients with metastatic renal cell carcinoma (mRCC) who received combined treatment with IL-2, interferon-?-2a and dendritic cell vaccine. We examined gene expression, cytokine levels in patient serum and lymphocyte subsets as determined by flow cytometry (FCM). Pre-treatment PBLs from patients with mRCC exhibit a gene expression profile and serum cytokine profile consistent with inflammation and proliferation not found in healthy donors (HD). PBL gene expression from patients with mRCC showed increased mRNA of genes involved with T-cell and TREG-cell activation pathways, which was also reflected in lymphocyte subset distribution. Overall, PBL gene expression post-treatment (POST) was not significantly different than pre-treatment (PRE). Nevertheless, treatment related changes in gene expression (post-treatment minus pre-treatment) revealed an increased expression of T-cell and B-cell receptor signaling pathways in responding (R) patients compared to non-responding (NR) patients. In addition, we observed down-regulation of TREG-cell pathways post-treatment in R vs. NR patients. While exploratory in nature, this study supports the hypothesis that enhanced inflammatory cytotoxic pathways coupled with blunting of the regulatory pathways is necessary for effective anti-cancer activity associated with immune therapy. This type of analysis can potentially identify additional immune therapeutic targets in patients with mRCC. 相似文献
102.
Izquierdo-Useros N Lorizate M Contreras FX Rodriguez-Plata MT Glass B Erkizia I Prado JG Casas J Fabriàs G Kräusslich HG Martinez-Picado J 《PLoS biology》2012,10(4):e1001315
HIV-1 is internalized into mature dendritic cells (mDCs) via an as yet undefined mechanism with subsequent transfer of stored, infectious virus to CD4+ T lymphocytes. Thus, HIV-1 subverts a DC antigen capture mechanism to promote viral spread. Here, we show that gangliosides in the HIV-1 membrane are the key molecules for mDC uptake. HIV-1 virus-like particles and liposomes mimicking the HIV-1 lipid composition were shown to use a common internalization pathway and the same trafficking route within mDCs. Hence, these results demonstrate that gangliosides can act as viral attachment factors, in addition to their well known function as cellular receptors for certain viruses. Furthermore, the sialyllactose molecule present in specific gangliosides was identified as the determinant moiety for mDC HIV-1 uptake. Thus, sialyllactose represents a novel molecular recognition pattern for mDC capture, and may be crucial both for antigen presentation leading to immunity against pathogens and for succumbing to subversion by HIV-1. 相似文献
103.
ABSTRACT: BACKGROUND: Use of plant resources and ecosystems practiced by indigenous peoples of Mesoamerica commonly involves domestication of plant populations and landscapes. Our study analyzed interactions of coexisting wild and managed populations of the pitaya Stenocereus pruinosus, a columnar cactus used for its edible fruit occurring in natural forests, silviculturally managed in milpa agroforestry systems, and agriculturally managed in homegardens of the Tehuacan Valley, Mexico. We aimed at analyzing criteria of artificial selection and their consequences on phenotypic diversity and differentiation, as well as documenting management of propagules at landscape level and their possible contribution to gene flow among populations. METHODS: Semi-structured interviews were conducted to 83 households of the region to document perception of variation, criteria of artificial selection, and patterns of moving propagules among wild and managed populations. Morphological variation of trees from nine wild, silviculturally and agriculturally managed populations was analyzed for 37 characters through univariate and multivariate statistical methods. In addition, indexes of morphological diversity (MD) per population and phenotypic differentiation (PD) among populations were calculated using character states and frequencies. RESULTS: People recognized 15 pitaya varieties based on their pulp color, fruit size, form, flavor, and thorniness. On average, in wild populations we recorded one variety per population, in silviculturally managed populations 1.58 +/- 0.77 varieties per parcel, and in agriculturally managed populations 2.19 +/- 1.12 varieties per homegarden. Farmers select in favor of sweet flavor (71% of households interviewed) and pulp color (46%) mainly red, orange and yellow. Artificial selection is practiced in homegardens and 65% of people interviewed also do it in agroforestry systems. People obtain fruit and branches from different population types and move propagules from one another. Multivariate analyses showed morphological differentiation of wild and agriculturally managed populations, mainly due to differences in reproductive characters; however, the phenotypic differentiation indexes were relatively low among all populations studied. Morphological diversity of S. pruinosus (average MD = 0.600) is higher than in other columnar cacti species previously analyzed. CONCLUSIONS: Artificial selection in favor of high quality fruit promotes morphological variation and divergence because of the continual replacement of plant material propagated and introduction of propagules from other villages and regions. This process is counteracted by high gene flow influenced by natural factors (pollinators and seed dispersers) but also by human management (movement of propagules among populations), all of which determines relatively low phenotypic differentiation among populations. Conservation of genetic resources of S. pruinosus should be based on the traditional forms of germplasm management by local people. 相似文献
104.
105.
Alyea RA Laurence SE Kim SH Katzenellenbogen BS Katzenellenbogen JA Watson CS 《Journal of neurochemistry》2008,106(4):1525-1533
The effects of 17β-estradiol (E2 ) on dopamine (DA) transport could explain gender and life-stage differences in the incidence of some neurological disorders. We tested the effects of E2 at physiological concentrations on DA efflux in nerve growth factor-differentiated rat pheochromocytoma cells that express estrogen receptors (ER) α, ERβ, and G-protein coupled receptor 30 (GPR30), and DA transporter (DAT). DAT efflux was determined as the transporter-specific loss of 3 H-DA from pre-loaded cells; a 9–15 min 10−9 M E2 treatment caused maximal DA efflux. Such rapid estrogenic action suggests a non-genomic response, and an E2 -dendrimer conjugate (limited to non-nuclear actions) caused DA efflux within 5 min. Efflux dose–responses for E2 were non-monotonic, also characteristic of non-genomic estrogenic actions. ERα siRNA knockdown abolished E2 -mediated DA efflux, while ERβ knockdown did not, and GPR30 knockdown increased E2 -mediated DA efflux (suggesting GPR30 is inhibitory). Use of ER-selective agonists/antagonists demonstrated that ERα is the predominant mediator of E2 -mediated DA efflux, with inhibitory contributions from GPR30 and ERβ. E2 also caused trafficking of ERα to the plasma membrane, trafficking of ERβ away from the plasma membrane, and unchanged membrane GPR30 levels. Therefore, ERα is largely responsible for non-genomic estrogenic effects on DAT activity. 相似文献
106.
Andrés Camou-Guerrero Victoria Reyes-García Miguel Martínez-Ramos Alejandro Casas 《Human ecology: an interdisciplinary journal》2008,36(2):259-272
We used a quantitative ethnobotanical approach to analyze factors influencing the use value of plant species among men and
women of the Rarámuri people in Cuiteco, Chihuahua, Mexico. We constructed a use value index (UV) combining the use frequency
(U) and the quality perception (Q) of useful plant species by local people. We identified all plant species used by the Rarámuri and classified them into 14
general use categories. We interviewed 34 households in the village to compare men and women’s knowledge on the five main
general use categories (and on their respective subcategories and specific uses), to document how they practice gathering
activities and to calculate scores of plants UV. A total of 226 useful plant species were identified, but only 12% of them
had high UV scores for the 42 specific uses defined. When the overall knowledge of plant species was examined, no significant differences
were detected between men and women, but significant differences were identified in general use categories such as medicinal
plants, plants for construction and domestic goods, but not in plants used as food and firewood. We identified a division
of labor in gathering activities associated with gender, with women mainly gathering medicinal and edible plants and being
involved in preparing medicines and food, whereas men were primarily gathering and using plants for manufacturing domestic
goods, firewood, and building materials. Plant species UV associated to gender were significantly different between men and
women at the level of specific uses in the general category of domestic goods and building. Frequency of use is highly associated
with plant species quality perception. 相似文献
107.
Background
Since 1990 non communicable diseases and injuries account for the majority of death and disability-adjusted life years in Latin America. We analyzed the relationship between the global burden of disease and Randomized Clinical Trials (RCTs) conducted in Latin America that were published in the five leading medical journals.Methodology/Principal Findings
We included all RCTs in humans, exclusively conducted in Latin American countries, and published in any of the following journals: Annals of Internal Medicine, British Medical Journal, Journal of the American Medical Association, Lancet, and New England Journal of Medicine. We described the trials and reported the number of RCTs according to the main categories of the global burden of disease. Sixty-six RCTs were identified. Communicable diseases accounted for 38 (57%) reports. Maternal, perinatal, and nutritional conditions accounted for 19 (29%) trials. Non-communicable diseases represent 48% of the global burden of disease but only 14% of reported trials. No trial addressed injuries despite its 18% contribution to the burden of disease in 2000.Conclusions/Significance
A poor correlation between the burden of disease and RCTs publications was found. Non communicable diseases and injuries account for up to two thirds of the burden of disease in Latin America but these topics are seldom addressed in published RCTs in the selected sample of journals. Funding bodies of health research and editors should be aware of the increasing burden of non communicable diseases and injuries occurring in Latin America to ensure that this growing epidemic is not neglected in the research agenda and not affected by publication bias. 相似文献108.
Casas JS Castellano EE Ellena J García-Tasende MS Pérez-Parallé ML Sánchez A Sánchez-González A Sordo J Touceda A 《Journal of inorganic biochemistry》2008,102(1):33-45
New Pd(II) and Pt(II) complexes [ML2] (HL=a substituted 2,5-dihydro-5-oxo-1H-pyrazolone-1-carbothioamide) have been synthesized by reacting K2MCl4 (M=Pd, Pt) or Pd(OAc)2 with beta-ketoester thiosemicarbazones. The structures of seven of these complexes were determined by X-ray diffraction. Although all exhibit a distorted square-planar coordination with trans- or (in one case) cis-[MN2S2] kernels, their supramolecular arrangements vary widely from isolated molecules to 3D-networks. The in vitro antitumoral assays performed with two HL ligands and their metal complexes showed significant cytostatic activity for the latter, with the most active [ML2] derivative (a palladium complex) being about sixteen times more active than cis-DDP against the cisplatinum-resistant cell line A2780cisR. 相似文献
109.
Bedia C Canals D Matabosch X Harrak Y Casas J Llebaria A Delgado A Fabriás G 《Chemistry and physics of lipids》2008,156(1-2):33-40
The acid ceramidase (AC) inhibitory activity of octanoylamides, p-tert-butylbenzamides and pivaloylamides of several 2-substituted aminoethanols is reported. All the aminoethanol amides bearing a hexadecyl substituent (C16), as well as (S)-N-(1-(hexadecylthio)-3-hydroxypropan-2-yl)pivaloylamide (SC16-tb) were inhibitory in cell lysates overexpressing AC, while all other compounds were not inhibitors. Kinetic experiments with (R,E)-N-(1-hydroxyoctadec-3-en-2-yl)pivaloylamide (E-tb) and SC16-tb showed that inhibition was competitive, with K(i) values of 34 and 94.0 microM, respectively. None of the compounds inhibited neutral ceramidase. Compounds E-tb and E-c7 (the octanoylamide of the unsaturated base E), which elicited a dose-response inhibition with IC(50) values around 15 microM, were the only AC inhibitors in intact cells. Both compounds were toxic to A549 cells with LD(50) values nearly 40 microM. Flow cytometry studies with E-tb evidenced that this compound induced a concentration-dependent cell cycle arrest at G(1) and a 20-25% apoptosis/late apoptosis/necrosis after a 24-h incubation at 50 microM. In agreement with its activity as acidic ceramidase inhibitor, this effect was accompanied with an increase in the amounts of C14, C16 and C18 ceramides (LC-MS analyses), which suggested that these lipids may be responsible for the cytotoxic activity of E-tb. 相似文献
110.
Olivier Dangles Thomas Steinmann Dominique Pierre Fabrice Vannier Jérôme Casas 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2008,194(7):653-663
Understanding the relative contributions of the shape of a sensory organ and the arrangement of receptors to the overall performance of the organ has long been a challenge for sensory biologists. We tackled this issue using the wind-sensing system of crickets, the cerci, two conical abdominal appendages covered with arrays of filiform hairs. Scanning electron microscopy coupled with 3D reconstruction methods were used for mapping of all cercal filiform hairs. The hairs are arranged according to their diameter in a way that avoids collisions with neighbours during hair deflection: long hairs are regularly spaced, whereas short hairs are both randomly and densely distributed. Particle image velocimetry showed that the variation in diameter of the cercus along its length modifies the pattern of fluid velocities. Hairs are subject to higher air flow amplitudes at the base than at the apex of the cercus. The relative importance of interactions between receptors and the air flow around the organ may explain the performance of the cricket's cercal system: it is characterised by a high density of statistically non-interacting short hairs located at the base of the cercus where sensitivity to air currents is the highest. 相似文献