Maria Capul - Black Hawk County Health Department

I accomplished the following: -Presented and designed health presentations for Hispanic populations in topics, like breast cancer, cervical cancer, colon cancer and nutrition. -Redesigned “Care for Yourself Program” brochure to be more health literate -Enrolled Hispanic people for cancer screening programs -Helped Spanish community navigate their environment both health and non health needs. -Shadowed and assisted the Nutrition department and the Refugee clinic -Translated enrollment forms for the STD Clinichttps://scholarworks.uni.edu/koob_recipients/1024/thumbnail.jp

Genetic Metabolic Complementation establishes a requirement for GDP-fucose in <i>Leishmania</i>

To survive in its sand fly vector, the trypanosomatid protozoan parasite Leishmania first attaches to the midgut to avoid excretion, but eventually it must detach for transmission by the next bite. In Leishmania major strain Friedlin, this is controlled by modifications of the stage-specific adhesin lipophosphoglycan (LPG). During differentiation to infective metacyclics, d-arabinopyranose (d-Arap) caps the LPG side-chain galactose residues, blocking interaction with the midgut lectin PpGalec, thereby leading to parasite detachment and transmission. Previously, we characterized two closely related L. major genes (FKP40 and AFKP80) encoding bifunctional proteins with kinase/pyrophosphorylase activities required for salvage and conversion of l-fucose and/or d-Arap into the nucleotide-sugar substrates required by glycosyltransferases. Whereas only AFKP80 yielded GDP-d-Arap from exogenous d-Arap, both proteins were able to salvage l-fucose to GDP-fucose. We now show that Δafkp80− null mutants ablated d-Arap modifications of LPG as predicted, whereas Δfkp40− null mutants resembled wild type (WT). Fucoconjugates had not been reported previously in L. major, but unexpectedly, we were unable to generate fkp40−/afkp80− double mutants, unless one of the A/FKPs was expressed ectopically. To test whether GDP-fucose itself was essential for Leishmania viability, we employed “genetic metabolite complementation.” First, the trypanosome de novo pathway enzymes GDP-mannose dehydratase (GMD) and GDP-fucose synthetase (GMER) were expressed ectopically; from these cells, the Δfkp40−/Δafkp80− double mutant was now readily obtained. As expected, the Δfkp40−/Δafkp80−/+TbGMD-GMER line lacked the capacity to generate GDP-Arap, while synthesizing abundant GDP-fucose. These results establish a requirement for GDP-fucose for L. major viability and predict the existence of an essential fucoconjugate(s)

Deficiency of Leishmania phosphoglycans influences the magnitude but does not affect the quality of secondary (memory) anti-Leishmania immunity

Despite inducing very low IFN-γ response and highly attenuated in vivo, infection of mice with phosphoglycan (PG) deficient Leishmania major (lpg2-) induces protection against virulent L. major challenge. Here, we show that mice infected with lpg2- L. major generate Leishmania-specific memory T cells. However, in vitro and in vivo proliferation, IL-10 and IFN-γ production by lpg2- induced memory cells were impaired in comparison to those induced by wild type (WT) parasites. Interestingly, TNF recall response was comparable to WT infected mice. Despite the impaired proliferation and IFN-γ response, lpg2- infected mice were protected against virulent L. major challenge and their T cells mediated efficient infection-induced immunity. In vivo depletion and neutralization studies with mAbs demonstrated that lpg2- L. major-induced resistance was strongly dependent on IFN-γ, but independent of TNF and CD8(+) T cells. Collectively, these data show that the effectiveness of secondary anti-Leishmania immunity depends on the quality (and not the magnitude) of IFN-γ response. These observations provide further support for consideration of lpg2- L. major as a live-attenuated candidate for leishmanization in humans since it protects strongly against virulent challenge, without inducing pathology in infected animals

Estructura de la red trófica y simulaciones dinámicas en el ecosistema de arrecife rocoso de Yelapa, Pacífico mexicano

Background. Ecological Network Analysis has been used for defining aspects concerning the structure, health, and dynamics of marine ecosystems. Objectives. Evaluate the ecosystem’s structure, organization, and matu-rity in the shallow rocky reef ecosystem in Yelapa. Also, we determine the most affected functional groups by disturbances simulated and those which generate less resilience in the ecosystem. Methods. A mass-balan-ce trophic model Ecopath with Ecosim, was constructed, and Ascendency›s theory was used to evaluate the ecosystem properties. A Mixed Trophic Impacts matrix was used to assess direct and indirect trophic effects on the network. The functional groups more sensitive to disturbances were determined using Ecosim dynamics simulations in the short and long term with two mortality scenarios (an increase of 25 % and 50 %). Finally, the System Recovery Time was used as a measure of resilience. Results. The Yelapa rocky-reef ecosystem ex-hibits the feature of a mature, organized, and developing ecosystem but is less resistant to disturbances. Several fish groups, zooplankton, and phytoplankton produced the most remarkable effects in the trophic network. In addition, the phytoplankton, chlorophyta, and the group of other benthic invertebrates propagated more effects on other model components. Conclusions. Yelapa rocky reef would lose resilience if the functional groups eels &amp; morays, other benthic invertebrates, snappers, and phytoplankton were disturbed.Antecedentes. Los análisis ecológicos de redes han sido usados para definir aspectos relacionados a la es-tructura, salud y dinámica de los ecosistemas marinos. Objetivos. Evaluar la estructura, organización y madurez en el ecosistema de Yelapa, un arrecife rocoso somero. También, se determinaron los grupos funcionales que podrían ser más sensibles a perturbaciones simuladas y aquellos que generan menor resiliencia en el ecosis-tema. Métodos. Se construyó un modelo trófico de balance de masas Ecopath con Ecosim y se usó la teoría de Ascendency para evaluar las propiedades ecosistémicas. La matriz de Impacto Trófico Mixto evaluó los efectos tróficos directos e indirectos en la red. Se determinaron los grupos funcionales más sensibles a perturbaciones usando simulaciones dinámicas Ecosim de corto y largo tiempo con dos escenarios de mortalidad (incremento del 25 % y 50 %). Finalmente, se empleó el Tiempo de Recuperación del Sistema como una medida de resiliencia. Resultados. El ecosistema arrecifal rocoso de Yelapa exhibió características de un ecosistema maduro, organizado y desarrollado, pero a su vez menos resistente a perturbaciones. Diferentes grupos de peces, zooplancton y fitoplancton generaron los mayores efectos en la red trófica. Además, el fitoplancton, clorofitas y el grupo de otros invertebrados bentónicos propagaron los mayores efectos hacia los otros componentes del sistema. Yelapa es menos resiliente cuando son perturbados los grupos funcionales de anguilas y morenas, otros invertebrados bentónicos, pargos y fitoplancton. Conclusiones. Grupos funcionales de distintos niveles tróficos fueron prioritarios para preservar la integridad estructural del ecosistema, las condiciones de madurez, desarrollo y resiliencia. Este estudio representa el primer paso para analizar las propiedades de la red trófica y especies ecológicamente relevantes entre el ecosistema de coral somero y profundo en Yelapa

Differential impact of LPG-and PG-deficient Leishmania major mutants on the immune response of human dendritic cells

<div><p>Background</p><p><i>Leishmania major</i> infection induces robust interleukin-12 (IL12) production in human dendritic cells (hDC), ultimately resulting in Th1-mediated immunity and clinical resolution. The surface of <i>Leishmania</i> parasites is covered in a dense glycocalyx consisting of primarily lipophosphoglycan (LPG) and other phosphoglycan-containing molecules (PGs), making these glycoconjugates the likely pathogen-associated molecular patterns (PAMPS) responsible for IL12 induction.</p><p>Methodology/Principal Findings</p><p>Here we explored the role of parasite glycoconjugates on the hDC IL12 response by generating <i>L</i>. <i>major</i> Friedlin V1 mutants defective in LPG alone, (FV1 <i>lpg1-</i>), or generally deficient for all PGs, (FV1 <i>lpg2-</i>). Infection with metacyclic, infective stage, <i>L</i>. <i>major</i> or purified LPG induced high levels of <i>IL12B</i> subunit gene transcripts in hDCs, which was abrogated with FV1 <i>lpg1-</i> infections. In contrast, hDC infections with FV1 <i>lpg2-</i> displayed increased <i>IL12B</i> expression, suggesting other PG-related/<i>LPG2</i> dependent molecules may act to dampen the immune response. Global transcriptional profiling comparing WT, FV1 <i>lpg1-</i>, FV1 <i>lpg2-</i> infections revealed that FV1 <i>lpg1-</i> mutants entered hDCs in a silent fashion as indicated by repression of gene expression. Transcription factor binding site analysis suggests that LPG recognition by hDCs induces IL-12 in a signaling cascade resulting in Nuclear Factor κ B (NFκB) and Interferon Regulatory Factor (IRF) mediated transcription.</p><p>Conclusions/Significance</p><p>These data suggest that <i>L</i>. <i>major</i> LPG is a major PAMP recognized by hDC to induce IL12-mediated protective immunity and that there is a complex interplay between PG-baring <i>Leishmania</i> surface glycoconjugates that result in modulation of host cellular IL12.</p></div

Cine y enseñanza de la enfermería

[ES]El propósito de este trabajo es proporcionar algunas ideas sobre la importancia del cine, con su narrativa audiovisual, en la enseñanza de la enfermería. El uso del cine en la enseñanza brinda la posibilidad de potenciar la construcción de la mirada profesional. La carrera de enfermería de la Universidad Isalud de la República Argentina plantea el trabajo sistemático con relatos cinematográficos. En este caso se presentan diversas modalidades de trabajo con relatos cinematográficos en el espacio curricular de Fundamentos de Enfermería de la carrera de Enfermero/a Profesional de la Universidad Isalud.[EN]The purpose of this paper is to provide some ideas about the importance of film, with it’s audiovisual narrative, in the nursing education. The use of films during teaching gives the posibility to increase the construction of a professional view. The nursing carreer of Isalud University of Argentina is founded a sistematic work with cinematographic support. In this case are presented different ways of work with cinematographic support in a curricular space of Fundamentals of Nursing of the career of a professional Nurse of the Isalud University

Leishmania major Survival in Selective Phlebotomus papatasi Sand Fly Vector Requires a Specific SCG-Encoded Lipophosphoglycan Galactosylation Pattern

Phlebotomine sand flies that transmit the protozoan parasite Leishmania differ greatly in their ability to support different parasite species or strains in the laboratory: while some show considerable selectivity, others are more permissive. In “selective” sand flies, Leishmania binding and survival in the fly midgut typically depends upon the abundant promastigote surface adhesin lipophosphoglycan (LPG), which exhibits species- and strain-specific modifications of the dominant phosphoglycan (PG) repeat units. For the “selective” fly Phlebotomus papatasi PpapJ, side chain galactosyl-modifications (scGal) of PG repeats play key roles in parasite binding. We probed the specificity and properties of this scGal-LPG PAMP (Pathogen Associated Molecular Pattern) through studies of natural isolates exhibiting a wide range of galactosylation patterns, and of a panel of isogenic L. major engineered to express similar scGal-LPG diversity by transfection of SCG-encoded β1,3-galactosyltransferases with different activities. Surprisingly, both ‘poly-scGal’ and ‘null-scGal’ lines survived poorly relative to PpapJ-sympatric L. major FV1 and other ‘mono-scGal’ lines. However, survival of all lines was equivalent in P. duboscqi, which naturally transmit L. major strains bearing ‘null-scGal’-LPG PAMPs. We then asked whether scGal-LPG-mediated interactions were sufficient for PpapJ midgut survival by engineering Leishmania donovani, which normally express unsubstituted LPG, to express a ‘PpapJ-optimal’ scGal-LPG PAMP. Unexpectedly, these “L. major FV1-cloaked” L. donovani-SCG lines remained unable to survive within PpapJ flies. These studies establish that midgut survival of L. major in PpapJ flies is exquisitely sensitive to the scGal-LPG PAMP, requiring a specific ‘mono-scGal’ pattern. However, failure of ‘mono-scGal’ L. donovani-SCG lines to survive in selective PpapJ flies suggests a requirement for an additional, as yet unidentified L. major-specific parasite factor(s). The interplay of the LPG PAMP and additional factor(s) with sand fly midgut receptors may determine whether a given sand fly host is “selective” or “permissive”, with important consequences to both disease transmission and the natural co-evolution of sand flies and Leishmania

Degradation of Host Sphingomyelin Is Essential for Leishmania Virulence

In eukaryotes, sphingolipids (SLs) are important membrane components and powerful signaling molecules. In Leishmania, the major group of SLs is inositol phosphorylceramide (IPC), which is common in yeast and Trypanosomatids but absent in mammals. In contrast, sphingomyelin is not synthesized by Leishmania but is abundant in mammals. In the promastigote stage in vitro, Leishmania use SL metabolism as a major pathway to produce ethanolamine (EtN), a metabolite essential for survival and differentiation from non-virulent procyclics to highly virulent metacyclics. To further probe SL metabolism, we identified a gene encoding a putative neutral sphingomyelinase (SMase) and/or IPC hydrolase (IPCase), designated ISCL (Inositol phosphoSphingolipid phospholipase C-Like). Despite the lack of sphingomyelin synthesis, L. major promastigotes exhibited a potent SMase activity which was abolished upon deletion of ISCL, and increased following over-expression by episomal complementation. ISCL-dependent activity with sphingomyelin was about 20 fold greater than that seen with IPC. Null mutants of ISCL (iscl−) showed modest accumulation of IPC, but grew and differentiated normally in vitro. Interestingly, iscl− mutants did not induce lesion pathology in the susceptible BALB/c mice, yet persisted indefinitely at low levels at the site of infection. Notably, the acute virulence of iscl− was completely restored by the expression of ISCL or heterologous mammalian or fungal SMases, but not by fungal proteins exhibiting only IPCase activity. Together, these findings strongly suggest that degradation of host-derived sphingomyelin plays a pivotal role in the proliferation of Leishmania in mammalian hosts and the manifestation of acute disease pathology