The prominent role of neutrophils during the initial phase of infection by Leishmania parasites.

Neutrophils are rapidly and massively recruited to the site of Leishmania inoculation, where they phagocytose the parasites, some of which are able to survive within these first host cells. Neutrophils can thus provide a transient safe shelter for the parasites, prior to their entry into macrophages where they will replicate. In addition, neutrophils release and synthesize rapidly several factors including cytokines and chemokines. The mechanism involved in their rapid recruitment to the site of parasite inoculation, as well as the putative consequences of their massive presence on the microenvironment of the focus of infection will be discussed in the context of the development of the Leishmania-specific immune response

Argentinean pejerrey (Odonthestes bonariensis) : artificial feeding

Para comprobar la factibilidad de la alimentación artificial del pejerrey con pienso balanceado pelletizado y aproximar el porcentaje de proteína en la formulación se realizó un ensayo con cuatro tratamientos: testigo (T) sin alimento artificial, alimento de 24 % (P1), 32 % (P2) y 42 % de proteína (P3). Para ello se realizaron cuatro jaulas de 4x4 m, ubicadas en una represa de la zona de Tunuyán, provincia de Mendoza. En cada jaula se colocaron 100 pejerreyes de un peso medio de 64,8 gramos. Luego de tres me-ses de encierre y diez días de adaptación a la dieta, se alimentaron P1, P2 y P3 con una ración de 1 g por pez/día en 40 días. Los peces de estas parcelas aumentaron un pro-medio de 7,7 g/pez.día 40 días, mientras que los testigos bajaron 7,9 g/por pez en el mis-mo período. Dividiendo a los peces en categorías se pudo determinar que los de mayor tamaño crecían más. Los peces con pesos iniciales medios de 83,5; 60,3 y 47,8 g lograron un aumento de peso medio promedio respectivamente de 8,4; 2,6 y -3,2 g, con un máximo de aumento de 17,8 g en el caso de P1 y con pejerreyes de 78,3 g de peso. No se pudo realizar repeticiones ni prueba estadística debido a la mortandad producida por pájaros pescadores. Se puede afirmar que los pejerreyes toleran el encierro (7,8 peces/m3) y el manejo y aceptan los alimentos balanceados pelletizados, sobre todo los peces de peso vivo superior a 60 g.W ith the p urpo se o f verifyin g th e factibility of artificial feeding of «pejerrey» with balanced pelletized feed and approximating protein percentage in the feed formula, a trial was carried out with four treatments: control (T) without artificial feed, 24 % (P1), 32 % (P2), 42 % (P3) protein feed. Four 4x4 m cages were made and placed in a dam of Tunuyan zone in the province of Mendoza. One hundred pejerreyes 64,8 average weight was placed in each cage, and after a three month confinement adaptation period, and ten days of balanced diet, three lots were fed with a ration of 1 g/day/fish. These fishes gained an average weight of 7.7g/day in 40 days while the control group lost 7.9 g per fish in the same period. The fishes were classified according to weight. It could be reached the conclusion that heavier fishes grew up more. Initial 83.5; 60.3 and 47.8 average weight fishes gained 8.4, 2.6 and -3.2 g weight respectively, with a maximum of weigh t gain o f 17 .8 g in 7 8.3g weigh t pejerreyes of P1. Neither repetitions nor statistical analysis could be done because of the high mortality due to fishing birds. The pejerreyes tolerated confinement (7,8 fishes/m3) and handling well and accepted the arti-ficial feed.Fil: Tacchini, Fabio M. . Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Departamento de Producción AgropecuariaFil: Allende, Gabriel M. . Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Departamento de Producción AgropecuariaFil: Linares, Christian D. . Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Departamento de Producción AgropecuariaFil: Martínez, Gustavo M. . Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Departamento de Producción Agropecuari

Integrated RF-DC converter and PCB antenna for UHF wireless powering applications

In this work, a broadband differential RF-DC CMOS converter realized in CMOS 130 nm technology with a customized PCB antenna with inductive coupling feeding for RF energy scavenging is presented. Experimental results show that output DC voltage higher than 1V from 800MHz to 970MHz can be obtained with a load of 1kohm

Single-Ended Broadband Antenna for Radiofrequency Energy Harvesting

A single-ended broadband UHF antenna with high inductive input impedance for radiofrequency energy harvesting is here presented. It consists of a small feeding loop and a conical radiating monopole. A prototype has been fabricated on a FR4 substrate and tested. Experimental results show a -3dB power transmission bandwidth of about 130MHz (860MHz−990MHz)

Lack of the transcription factor hypoxia-inducible factor (HIF)-1α in macrophages accelerates the necrosis of Mycobacterium avium-induced granulomas

Accepted ManuscriptThe establishment of mycobacterial infection is characterized by the formation of granulomas, which are well-organized aggregates of immune cells, namely, infected macrophages. The granuloma's main function is to constrain and prevent dissemination of the mycobacteria while focusing the immune response to a limited area. In some cases these lesions can grow progressively into large granulomas which can undergo central necrosis, thereby leading to their caseation. Macrophages are the most abundant cells present in the granuloma and are known to adapt under hypoxic conditions in order to avoid cell death. Our laboratory has developed a granuloma necrosis model that mimics the human pathology of Mycobacterium tuberculosis, using C57BL/6 mice infected intravenously with a low dose of a highly virulent strain of Mycobacterium avium. In this work, a mouse strain deleted of the hypoxia inducible factor 1a (HIF-1a) under the Cre-lox system regulated by the lysozyme M gene promoter was used to determine the relevance of HIF-1a in the caseation of granulomas. The genetic ablation of HIF-1a in the myeloid lineage causes the earlier emergence of granuloma necrosis and clearly induces an impairment of the resistance against M. avium infection coincident with the emergence of necrosis. The data provide evidence that granulomas become hypoxic before undergoing necrosis through the analysis of vascularization and quantification of HIF-1a in a necrotizing mouse model. Our results show that interfering with macrophage adaptation to hypoxia, such as through HIF-1a inactivation, accelerates granuloma necrosis.Support from national funds through FCT/MEC (Fundação para a Ciência e a Tecnologia/Ministério da Educação e Ciência), when applicable cofunded by FEDER funds within the partnership agreement PT2020 related to the research unit number 4293; from “NORTE-07-0124-FEDER-000002-Host-Pathogen Interactions,” cofunded by Programa Operacional Regional do Norte (ON.2–O Novo Norte), under the Quadro de Referência Estratégico Nacional (QREN); and from HMSP-ICT/0024/2010. T.M.S. received postdoctoral grant ON2201310 from “NORTE-07-0124-FEDER-000002-Host-Pathogen Interactions,” cofunded by Programa Operacional Regional do Norte (ON.2–O Novo Norte), under the Quadro de Referência Estratégico Nacional (QREN). M.R. received Ph.D. grant SFRH/BD/89871/2012 from FCT, Portuga

IL-4Rα Signaling in Keratinocytes and Early IL-4 Production Are Dispensable for Generating a Curative T Helper 1 Response in Leishmania major-Infected C57BL/6 Mice.

Experimental infection with the protozoan parasite Leishmania major has been extensively used to understand the mechanisms involved in T helper cell differentiation. Following infection, C57BL/6 mice develop a small self-healing cutaneous lesion and they are able to control parasite burden, a process linked to the development of T helper (Th) 1 cells. The local presence of IL-12 has been reported to be critical in driving Th1 cell differentiation. In addition, the early secretion of IL-4 was reported to potentially contribute to Th1 cell differentiation. Following infection with L. major, early keratinocyte-derived IL-4 was suggested to contribute to Th1 cell differentiation. To investigate a putative autocrine role of IL-4 signaling on keratinocytes at the site of infection, we generated C57BL/6 mice deficient for IL-4Rα expression selectively in keratinocytes. Upon infection with L. major, these mice could control their inflammatory lesion and parasite load correlating with the development of Th1 effector cells. These data demonstrate that IL-4 signaling on keratinocytes does not contribute to Th1 cell differentiation. To further investigate the source of IL-4 in the skin during the first days after L. major infection, we used C57BL/6 IL-4 reporter mice allowing the visualization of IL-4 mRNA expression and protein production. These mice were infected with L. major. During the first 3 days after infection, skin IL-4 mRNA expression was observed selectively in mast cells. However, no IL-4 protein production was detectable locally. In addition, early IL-4 blockade locally had no impact on subsequent Th1 cell differentiation and control of the disease. Taken together, the present data rule out a major role for skin IL-4 and keratinocyte IL-4Rα signaling in the development of a Th1 protective immune response following experimental infection with L. major

PCSK9 Expression in Epicardial Adipose Tissue : Molecular Association with Local Tissue Inflammation

Epicardial adipose tissue (EAT) has the unique property to release mediators that nourish the heart in healthy conditions, an effect that becomes detrimental when volume expands and proinflammatory cytokines start to be produced. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a proinflammatory mediator involved in atherosclerosis, is also produced by visceral fat. Due to the correlation of inflammation with PCSK9 and EAT enlargement, we evaluated whether PCSK9 was expressed in EAT and associated with EAT inflammation and volume. EAT samples were isolated during surgery. EAT thickness was measured by echocardiography. A microarray was used to explore EAT transcriptoma. The PCSK9 protein levels were measured by Western Blot in EAT and ELISA in plasma. PCSK9 was expressed at both the gene and protein levels in EAT. We found a positive association with EAT thickness and local proinflammatory mediators, in particular, chemokines for monocytes and lymphocytes. No association was found with the circulating PCSK9 level. The expression of PCSK9 in EAT argues that PCSK9 is part of the EAT secretome and EAT inflammation is associated with local PCSK9 expression, regardless of circulating PCSK9 levels. Whether reducing EAT inflammation or PCSK9 local levels may have beneficial effects on EAT metabolism and cardiovascular risk needs further investigations

Correlative study on impaired prostaglandin E2 regulation in EAT and maladaptive cardiac remodeling via EPAC2 and ST2 signaling in overweight CVD subjects

There is recent evidence that the dysfunctional responses of a peculiar visceral fat deposit known as epicardial adipose tissue (EAT) can directly promote cardiac enlargement in the case of obesity. Here, we observed a newer molecular pattern associated with LV dysfunction mediated by prostaglandin E2 (PGE(2)) deregulation in EAT in a cardiovascular disease (CVD) population. A series of 33 overweight CVD males were enrolled and their EAT thickness, LV mass, and volumes were measured by echocardiography. Blood, plasma, EAT, and SAT biopsies were collected for molecular and proteomic assays. Our data show that PGE(2) biosynthetic enzyme (PTGES-2) correlates with echocardiographic parameters of LV enlargement: LV diameters, LV end diastolic volume, and LV masses. Moreover, PTGES-2 is directly associated with EPAC2 gene (r = 0.70, p < 0.0001), known as a molecular inducer of ST2/IL-33 mediators involved in maladaptive heart remodelling. Furthermore, PGE(2) receptor 3 (PTEGER3) results are downregulated and its expression is inversely associated with ST2/IL-33 expression. Contrarily, PGE(2) receptor 4 (PTGER4) is upregulated in EAT and directly correlates with ST2 molecular expression. Our data suggest that excessive body fatness can shift the EAT transcriptome to a pro-tissue remodelling profile, may be driven by PGE(2) deregulation, with consequent promotion of EPAC2 and ST2 signalling

Notch regulates Th17 differentiation and controls trafficking of IL-17 and metabolic regulators within Th17 cells in a context-dependent manner.

Th17 cells play critical roles in host defense and autoimmunity. Emerging data support a role for Notch signaling in Th17 cell differentiation but whether it is a positive or negative regulator remains unclear. We report here that T cell-specific deletion of Notch receptors enhances Th17 cell differentiation in the gut, with a corresponding increase in IL-17 secretion. An increase in Th17 cell frequency was similarly observed following immunization of T cell specific Notch mutant mice with OVA/CFA. However, in this setting, Th17 cytokine secretion was impaired, and increased intracellular retention of IL-17 was observed. Intracellular IL-17 co-localized with the CD71 iron transporter in the draining lymph node of both control and Notch-deficient Th17 cells. Immunization induced CD71 surface expression in control, but not in Notch-deficient Th17 cells, revealing defective CD71 intracellular transport in absence of Notch signaling. Moreover, Notch receptor deficient Th17 cells had impaired mTORC2 activity. These data reveal a context-dependent impact of Notch on vesicular transport during high metabolic demand suggesting a role for Notch signaling in the bridging of T cell metabolic demands and effector functions. Collectively, our findings indicate a prominent regulatory role for Notch signaling in the fine-tuning of Th17 cell differentiation and effector function