Myeloid expression of adenosine a2A receptor suppresses T and NK cell responses in the solid tumor microenvironment

High concentrations of adenosine in tumor microenvironments inhibit antitumor cytotoxic lymphocyte responses. Although T cells express inhibitory adenosine A2A receptors (A2AR) that suppress their activation and inhibit immune killing of tumors, a role for myeloid cell A2ARs in suppressing the immune response to tumors has yet to be investigated. In this study, we show that the growth of transplanted syngeneic B16F10 melanoma or Lewis lung carcinoma cells is slowed in Adora2af/f-LysMCre+/- mice, which selectively lack myeloid A2ARs. Reduced melanoma growth is associated with significant increases in MHCII and IL12 expression in tumor-associated macrophages and with >90% reductions in IL10 expression in tumor-associated macrophages, dendritic cells (DC), and Ly6C+ or Ly6G+ myeloid-derived suppressor cells (MDSC). Myeloid deletion of A2ARs significantly increases CD44 expression on tumor-associated T cells and natural killer (NK) cells. Depletion of CD8+ T cells or NK cells in tumor-bearing mice indicates that both cell types initially contribute to slowing melanoma growth in mice lacking myeloid A2A receptors, but tumor suppression mediated by CD8+ T cells is more persistent. Myeloid-selective A2AR deletion significantly reduces lung metastasis of melanomas that express luciferase (for in vivo tracking) and ovalbumin (as a model antigen). Reduced metastasis is associated with increased numbers and activation of NK cells and antigen-specific CD8+ T cells in lung in filtrates. Overall, the findings indicate that myeloid cell A2ARs have direct myelosuppressive effects that indirectly contribute to the suppression of T cells and NK cells in primary and metastatic tumor microenvironments. The results indicate that tumor-associated myeloid cells, including macrophages, DCs, and MDSCs all express immunosuppressive A2ARs that are potential targets of adenosine receptor blockers to enhance immune killing of tumors. ©2014 AACR

Characterization of Mathematical Reasoning Skills in Children with ADHD

The objective of the present research was to characterize the mathematical reasoning skills in children with ADHD between 7 and 9 years old. The study begins with the conception of children with special needs and an anthropological research is carried out in perspectives of the actor on mathematical reasoning skills and interviews of their three teachers about their difficulties, alterations and disorders. The research method is an ethnographic fieldwork. The results show lack of mathematical skills specifically in numerical calculation; observing disorder, combination of simultaneous operation between addition and subtraction, attention deficit during the reading of a problem so they fail to systematize, identify data for algorithmic operationsEl objetivo de la presente investigación fue caracterizar las habilidades del razonamiento matemático en niños con TDAH entre 7 a 9 años, el estudio inicia de la concepción de niños con necesidades especiales y se realiza una indagación antropológica en perspectivas del actor sobre las habilidades del razonamiento matemático y las entrevista a sus tres docentes acerca de sus dificultades, alteraciones y trastornos. El método de la investigación es el trabajo de campo etnográfico. Los resultados muestran carencia de habilidades matemáticas específicamente en cálculo numérico; apreciándose desorden, combinación de operación simultáneamente entre adición y sustracción, déficit de atención durante la lectura de un problema por lo que no logran sistematizar, identificar los datos para las operaciones algorítmic

An early Little Ice Age brackish water invasion along the south coast of the Caspian Sea (sediment of Langarud wetland) and its wider impacts on environment and people

Caspian Sea level has undergone significant changes through time with major impacts not only on the surrounding coasts, but also offshore. This study reports a brackish water invasion on the southern coast of the Caspian Sea constructed from a multi-proxy analysis of sediment retrieved from the Langarud wetland. The ground surface level of wetland is >6 m higher than the current Caspian Sea level (at -27.41 m in 2014) and located >11 km far from the coast. A sequence covering the last millennium was dated by three radiocarbon dates. The results from this new study suggest that Caspian Sea level rose up to at least -21.44 m (i.e. >6 m above the present water level) during the early Little Ice Age. Although previous studies in the southern coast of the Caspian Sea have detected a high-stand during the Little Ice Age period, this study presents the first evidence that this high-stand reached so far inland and at such a high altitude. Moreover, it confirms one of the very few earlier estimates of a high-stand at -21 m for the second half of the 14th century. The effects of this large-scale brackish water invasion on soil properties would have caused severe disruption to regional agriculture, thereby destabilizing local dynasties and facilitating a rapid Turko-Mongol expansion of Tamerlane’s armies from the east.N Ghasemi (INIOAS), V Jahani (Gilan Province Cultural Heritage and Tourism Organisation) and A Naqinezhad (University of Mazandaran), INQUA QuickLakeH project (no. 1227) and to the European project Marie Curie, CLIMSEAS-PIRSES-GA-2009-24751

Evaluation of repeat distal transradial access in the anatomic snuffbox

PurposeThere is increasing interest in the distal radial artery in the anatomic snuffbox as an alternative arterial access point, but the durability of the distal radial artery to support repetitive accesses over multiple procedures is not well established. The purpose of this study was therefore to evaluate success rates for repeated left-sided distal transradial access (ldTRA) in the anatomic snuffbox.MethodsIn this single institution retrospective study, all patients undergoing radioembolization treatments from January 1st, 2019 to May 1st, 2020 were prospectively evaluated for ldTRA. ldTRA was performed by 15 different operators. Exclusion criteria were a left radiocephalic hemodialysis fistula, inability to properly position the arm, Barbeau D waveform, or failed prior ldTRA due to tortuosity. Barbeau patterns, arterial sizes, and success rates at the first, second, and third ldTRA were compared.ResultsFifty patients were evaluated for ldTRA and 44, 39, and 10 underwent one, two, and three ldTRA attempts for a total of 93 procedures. There was no significant change in Barbeau patterns between the first and second (p = 0.13) or first and third (p = 1.0) ldTRA. There was no significant change in artery size between the first (mean, 2.3 mm; range, 1.5–3.4 mm) and second (mean, 2.3 mm; range, 1.6–3.3 mm) (p = 0.59) and first and third (mean, 2.4 mm; range, 1.9–3.3) (p = 0.45) ldTRA. The success rate was not significantly different between the first (93%, 41/44, 95% CI 81%–99%), second (95%, 37/39, 95% CI 83%–99%), and third (100%, 10/10, 95% CI 69%–100%) procedure (p = 1.0). The asymptomatic occlusion rate was 4.1% (2/49, 95% CI 0%–14%), and subsequent ldTRA was successfully completed in both patients with occlusions. There were no hemorrhagic or ischemic complications.ConclusionSuccess rates are indistinguishable among first, second, and third time ldTRA suggesting that this is a durable access point

Perfil Proyecto nacional de prevención de influenza aviar

El proyecto se ha estructurado en cuatro componentes; estos son: Prevención de Ingreso de la IA y Vigilancia Epidemiológica; Control y Erradicación de la IA; Capacidad Diagnóstica; y Sistema Comunicacional del Riesgo e Informática. Los beneficiarios, entre otros, incluyen: la población humana, desde el punto de vista de la salud pública y de seguridad alimentaria; el patrimonio zoosanitario avícola del país; el SAG, al ver fortalecida su capacidad como prestatario de servicios públicos que procuran prevenir la IA

Many pion decays of rho(770) and omega(782) mesons in chiral theory

The decays rho(770) to 4 pi and omega(782) to 5pi are considered in detail in the approach based on the Weinberg Lagrangian obtained upon the nonlinear realization of chiral symmetry, added with the term induced by the anomalous Lagrangian of Wess and Zumino. The partial widths and excitation curves of the decays rho^0 to 2 pi^+ 2 pi^-, pi^+ pi^- 2 pi^0, rho^{+-} to 2 pi^{+-} pi^{-+} pi^0, rho^(+-} to pi^(+-} 3 pi^0 are evaluated for e^+e^- annihilation, photoproduction and tau lepton decays. The results of calculations are compared with the recent CMD-2 data on the decay rho^0 to 2 pi^+ 2 pi^- observed in e^+e^- annihilation. The omega to 5 pi decay widths and excitation curves in e^+e^- annihilation are obtained. The angular distributions for various combinations of the final pions in the decays rho to 4 pi and omega to 5 pi are written. The perspectives of the experimental study of the above decays in e^+e^- annihilation, tau lepton decays and photoproduction are discussed.Comment: Revtex, 32 pages including 11 ps figures. Replaced to fit the version published in Phys. Rev. D. Material rearranged, clarifying remarks and references added, typos fixe

Nitric Oxide-Induced Activation of the AMP-Activated Protein Kinase α2 Subunit Attenuates IκB Kinase Activity and Inflammatory Responses in Endothelial Cells

BACKGROUND: In endothelial cells, activation of the AMP-activated protein kinase (AMPK) has been linked with anti-inflammatory actions but the events downstream of kinase activation are not well understood. Here, we addressed the effects of AMPK activation/deletion on the activation of NFκB and determined whether the AMPK could contribute to the anti-inflammatory actions of nitric oxide (NO). METHODOLOGY/PRINCIPAL FINDINGS: Overexpression of a dominant negative AMPKα2 mutant in tumor necrosis factor-α-stimulated human endothelial cells resulted in increased NFκB activity, E-selectin expression and monocyte adhesion. In endothelial cells from AMPKα2(-/-) mice the interleukin (IL)-1β induced expression of E-selectin was significantly increased. DETA-NO activated the AMPK and attenuated NFκB activation/E-selectin expression, effects not observed in human endothelial cells in the presence of the dominant negative AMPK, or in endothelial cells from AMPKα2(-/-) mice. Mechanistically, overexpression of constitutively active AMPK decreased the phosphorylation of IκB and p65, indicating a link between AMPK and the IκB kinase (IKK). Indeed, IKK (more specifically residues Ser177 and Ser181) was found to be a direct substrate of AMPKα2 in vitro. The hyper-phosphorylation of the IKK, which is known to result in its inhibition, was also apparent in endothelial cells from AMPKα2(+/+) versus AMPKα2(-/-) mice. CONCLUSIONS: These results demonstrate that the IKK is a direct substrate of AMPKα2 and that its phosphorylation on Ser177 and Ser181 results in the inhibition of the kinase and decreased NFκB activation. Moreover, as NO potently activates AMPK in endothelial cells, a portion of the anti-inflammatory effects of NO are mediated by AMPK

Luchadoras del agro hondureño, historias cortas que inspiran a estar unidos por el agro

Reune ocho testimonios de mujeres hondureñas con relación a sus experiencias de participación y desarrollo en el sector agrario y rura

Manejo de la mosca minadora (Liriomyza huidobrensis) en el cultivo de la papa

Explicación breve del control de la mosca minadora en los cultivos de papa. Describe el ciclo de vida, las medidas de control y el control químic