Usefulness of the Nonself-Self Algorithm of HLA Epitope Immunogenicity in the Specificity Analysis of Monospecific Antibodies Induced during Pregnancy

Background HLAMatchmaker is a program to analyze the epitope specificities of HLA antibodies. It considers each HLA allele as a string of eplets. Intralocus and interlocus comparisons between donor and recipient alleles offer a structural assessment of compatibility and an analysis of allele panel reactivity patterns can generate information about epitope specificities of HLA antibodies. However, HLAMatchmaker cannot always generate conclusive interpretations of reactivity patterns of all monospecific antibodies which by definition recognize single epitopes. Hypothesis We have therefore developed a new antibody analysis approach that utilizes the nonself-self algorithm of HLA epitope immunogenicity. It is based in the concept that HLA antibodies originate from B-cells with immunoglobulin receptors to self HLA epitopes on one given allele and which can be activated by epitopes defined by a few nonself residue differences whereas the remainder of the structural epitope of the immunizing allele consists of self residues. Methods Three human monoclonal class I antibodies from HLA typed women sensitized during pregnancy were tested in Ig-binding assays with single alleles on a Luminex platformFindings Three new HLA epitopes were identified; they are defined by combinations of nonself and self residues for one allele of the antibody producer. Conclusion The nonself-self paradigm of HLA epitope immunogenicity offers a second approach to analyze HLA antibody specificities

Analysis of microtubule movement on isolated Xenopus egg cortices provides evidence that the cortical rotation involves dynein as well as Kinesin Related Proteins and is regulated by local microtubule polymerisation

AbstractIn amphibians, the cortical rotation, a translocation of the egg cortex relative to the cytoplasm, specifies the dorsoventral axis. The cortical rotation involves an array of subcortical microtubules whose alignment is mediated by Kinesin–related proteins (KRPs), and stops as M-phase promoting factor (MPF) activation propagates across the egg. To dissect the role of different motor proteins in the cortical rotation and to analyse their regulation, we have developed an open cell assay system involving reactivation of microtubule movement on isolated cortices. Microtubule movements were dependent on ATP and consisted mainly of wriggling and flailing without net displacement, consistent with a tethering of microtubules to the cortex. Reactivated movements were inhibited by anti-KRP and anti-dynein antibodies perfused together but not separately, the KRP antibody alone becoming fixed to the cortex. Neither antibody could inhibit movement in the presence of MPF, indicating that arrest of the cortical rotation is not due to MPF-dependent inhibition of motor molecules. In contrast, D2O treatment of live eggs to protect microtubules from progressive depolymerisation prolonged the cortical rotation. We conclude that the cortical rotation probably involves cytoplasmic dynein as well as cortical KRPs and terminates as a result of local MPF-dependent microtubule depolymerisation

Climate Change Impacts on the Patagonian Shelf Break Front

We characterize long-term trends of sea surface temperature (SST), absolute dynamic topography, and chlorophyll-a (CHL) in the Patagonian shelf break front (SBF) using 27 years (1993–2019) of satellite data. Warming of the Argentinean shelf waters and the southwestward displacement of the Brazil-Malvinas Confluence (BMC) impact the northernmost extension of the SBF. Cooling of the Malvinas Current (MC) and the concurrent warming of the adjacent shelf waters lead to a significant increase of SST gradients along the outer shelf. The southwestward displacement of the BMC implies a similar shift of the SBF. An increase in CHL trend appears to be associated with southerly wind anomalies along the shelf break. We estimate a southward shift of the northernmost penetration of the MC of −0.11 ± 0.076°/decade.Fil: Franco, Barbara Cristie. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Ruiz Etcheverry, Laura Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Marrari, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Piola, Alberto Ricardo. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval. Departamento Oceanografía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Matano, R. P.. State University of Oregon; Estados Unido

Non-pegylated liposomal doxorubicin plus ifosfamide in metastatic soft tissue sarcoma: results from a phase-II trial

Non-pegylated liposomal doxorubicin (NPLD) has demonstrated antitumour activity equivalent to conventional doxorubicin and a significantly lower risk of cardiotoxicity. This phase II trial was performed to evaluate the activity and the safety of NPLD and ifosfamide combination in patients with metastatic soft tissue sarcoma

Universidad y tecnologías: el conocimiento en la sociedad de la información y el aprendizaje colaborativo

Este trabajo continúa la línea de investigaciones propias anteriores que aborda la problemática relacionada con la formación académica de calidad. En comunicaciones previas, se ha destacado que las TIC (Tecnologías de Información y Comunicación) son ya herramientas de uso frecuente en todos los ámbitos de la educación, que modifican las formas de aprender y enseñar - y también el acceso a la información y al conocimiento. Aún más, las Tecnologías de la Información han optimizado el acercamiento al conocimiento hasta llegar a su gestión, dando origen a las Tecnologías del Aprendizaje y del Conocimiento (TAC). Este “aprendizaje aumentado”, que además incluye las denominadas TEP (Tecnologías de Empoderamiento y Participación), lleva al docente a una búsqueda incesante de la integración de la tecnología en la enseñanza con el contenido tratado, combinando permanentemente decisiones pedagógicas con los conocimientos construidos en el aula. Se busca, entonces, posibilitar la incorporación de nuevas tecnologías que favorezcan ambos, el aprendizaje autónomo del estudiante universitario y su participación en la generación del conocimiento en un mundo de cambios constantes. Así, el propósito de nuestro trabajo consiste en evaluar las herramientas tecnológicas disponibles con el objeto de implementar dispositivos didácticos que tiendan a la formación de calidad de un estudiante activo, participativo e independiente.Dirección de Educación a Distancia, Innovación en el aula y TIC (EAD

Trends and variability in local abundances of sailfish Istiophorus platypterus in Pacific waters of Costa Rica: Controls and effects on recreational fisheries

Fishing tourism represents a vital industry in Costa Rica, generating over US$520 million and attracting 150,000 tourists every year. The main objective of this study is to examine trends and variability in local abundances of sailfish Istiophorus platypterus, the main sportfish in Pacific waters of Costa Rica, and quantify the influence of environmental and anthropogenic factors. We compiled and analyzed sailfish information collected from sportfishing operations. Sailfish abundances were examined in relation to environmental conditions and commercial fishing. Timeseries analyses showed significant declining trends in local abundances of sailfish in the southern and central Pacific of Costa Rica over the last decade. Bycatch records from the commercial purse seine fleet operating in Costa Rican waters also show a declining trend in sailfish numbers. On the other hand, commercial landings from the national longline fleet show a significant increase of 108%, on average, over the past decade. Different numerical models indicated that fishing pressure from the national fleet and also sea surface temperature with different time lags affect local abundances of sailfish. While other countries in Central and North America protect sailfish and other species of tourist interest, Costa Rica still allows the landing and sales of billfishes as seafood. The results presented in this study highlight the need to allow for the recovery of local abundances of sailfish and promote the development of the coastal communities that depend on marine tourism as their main source of income

High-dose continuous-infusion ifosfamide in advanced well-differentiated/dedifferentiated liposarcoma

BACKGROUND: Liposarcomas represent the most common histological type of soft-tissue sarcomas (STS). Its main subgroups, WD/DD, is known to be poorly sensitive to chemotherapy, with few active agents, i.e., anthracyclines +/- ifosfamide and trabectedin. High-dose ifosfamide (HDIFX >12 g/m2) is active in STS pts pretreated with standard-dose IFX, though with greater toxicity. A prolonged continuous-infusion (ci) through a portable external pump may be an alternative way to administer HDIFX. METHODS: From March 2002 to August 2013, 28 pts (median age =60, range =37-73 yrs) with advanced disease (6 WD and 22 WD/DD) were given ciHDIFX, at the dose of 14 g/m2 as a 14-day continuous infusion every 4 weeks. Twenty-four pts (86%) were previously treated with chemotherapy (19 with anthracyclines and ifosfamide; 4 with anthracycline monotherapy; 1 with trabectedin). RESULTS: Seven PR (all in DDLPS), 2 minor response (MR) and 11 SD were observed. Of interest, 6 of 9 patients with PR or MR had had SD with the previous therapy with anthracycline plus ifosfamide. The median progression-free survival was 7 months. Most common side effects were mild myelosuppression (anemia G2-3 in 3 pts; G2-3 neutropenia in 3 pts and G4 in 1; G3 thrombocytopenia in 1 pt); nausea (G3 in 3 pts) and fatigue (G3 in 6 pts). One pts had transient G3 confusion. CONCLUSIONS: These data suggest that ciHDIFX is active in WD/DDLPS, even in patients already treated with a combination of anthracyclines plus ifosfamide. In this series, ciHDIFX regimen was better tolerated than HDIFX in published studies

Nuevas herramientas digitales: hacia una educación tecno-participativa

Este proyecto continúa la línea de investigación que aborda la problemática relacionada con el manejo de nuevos lenguajes en la formación académica de calidad, iniciada en uno anterior denominado B-173-La Integración de Nuevos Lenguajes en la Formación Académica del Profesional en Comercio Internacional. En el mismo se advierte que las TIC (Tecnologías de Información y Comunicación) se han convertido en herramientas de uso frecuente en todos los ámbitos de la educación, modificando tanto la forma de aprender y de enseñar, como la manera de acceder a la información y al conocimiento. Aún más, ya ha sido comprobado que las Tecnologías de la Información han optimizado el acercamiento al conocimiento hasta llegar a su gestión, dando origen a las Tecnologías del Aprendizaje y del Conocimiento, también denominadas TAC. Este “aprendizaje aumentado”, que además incluye las denominadas TEP (Tecnologías de Empoderamiento y Participación), lleva al docente a una búsqueda incesante de la integración de la tecnología en la enseñanza con el contenido tratado, combinando permanentemente decisiones pedagógicas con los conocimientos construidos en el aula. Se busca, entonces, posibilitar la incorporación de nuevas tecnologías que favorezcan ambos, el aprendizaje autónomo del estudiante universitario y su participación en la generación del conocimiento en un mundo de cambios constantes. Así, el propósito de nuestro trabajo consiste en evaluar las herramientas tecnológicas disponibles con el objeto de implementar dispositivos didácticos que tiendan a la formación de calidad de un estudiante activo, participativo e independiente.Fil: Galardo, Osvaldo Jorge. Universidad Nacional de La Matanza; Argentina.Fil: Dubouloy, María Angélica. Universidad Nacional de La Matanza; Argentina.Fil: Gimeno, Claudio Joaquín. Universidad Nacional de La Matanza; Argentina.Fil: Grillo, Laura Marcela. Universidad Nacional de La Matanza; Argentina.Fil: Marrari, Andrea Fabiana. Universidad Nacional de La Matanza; Argentina.Fil: Massimo, Adriana Inés. Universidad Nacional de La Matanza; Argentina.Fil: Prado, Andrea Paula. Universidad Nacional de La Matanza; Argentina

Immunologic risk stratification of pediatric heart transplant patients by combining HLA-EMMA and PIRCHE-II

Human leukocyte antigen (HLA) molecular mismatch is a powerful biomarker of rejection. Few studies have explored its use in assessing rejection risk in heart transplant recipients. We tested the hypothesis that a combination of HLA Epitope Mismatch Algorithm (HLA-EMMA) and Predicted Indirectly Recognizable HLA Epitopes (PIRCHE-II) algorithms can improve risk stratification of pediatric heart transplant recipients. Class I and II HLA genotyping were performed by next-generation sequencing on 274 recipient/donor pairs enrolled in the Clinical Trials in Organ Transplantation in Children (CTOTC). Using high-resolution genotypes, we performed HLA molecular mismatch analysis with HLA-EMMA and PIRCHE-II, and correlated these findings with clinical outcomes. Patients without pre-formed donor specific antibody (DSA) (n=100) were used for correlations with post-transplant DSA and antibody mediated rejection (ABMR). Risk cut-offs were determined for DSA and ABMR using both algorithms. HLA-EMMA cut-offs alone predict the risk of DSA and ABMR; however, if used in combination with PIRCHE-II, the population could be further stratified into low-, intermediate-, and high-risk groups. The combination of HLA-EMMA and PIRCHE-II enables more granular immunological risk stratification. Intermediate-risk cases, like low-risk cases, are at a lower risk of DSA and ABMR. This new way of risk evaluation may facilitate individualized immunosuppression and surveillance.</p

Immunologic risk stratification of pediatric heart transplant patients by combining HLA-EMMA and PIRCHE-II

Human leukocyte antigen (HLA) molecular mismatch is a powerful biomarker of rejection. Few studies have explored its use in assessing rejection risk in heart transplant recipients. We tested the hypothesis that a combination of HLA Epitope Mismatch Algorithm (HLA-EMMA) and Predicted Indirectly Recognizable HLA Epitopes (PIRCHE-II) algorithms can improve risk stratification of pediatric heart transplant recipients. Class I and II HLA genotyping were performed by next-generation sequencing on 274 recipient/donor pairs enrolled in the Clinical Trials in Organ Transplantation in Children (CTOTC). Using high-resolution genotypes, we performed HLA molecular mismatch analysis with HLA-EMMA and PIRCHE-II, and correlated these findings with clinical outcomes. Patients without pre-formed donor specific antibody (DSA) (n=100) were used for correlations with post-transplant DSA and antibody mediated rejection (ABMR). Risk cut-offs were determined for DSA and ABMR using both algorithms. HLA-EMMA cut-offs alone predict the risk of DSA and ABMR; however, if used in combination with PIRCHE-II, the population could be further stratified into low-, intermediate-, and high-risk groups. The combination of HLA-EMMA and PIRCHE-II enables more granular immunological risk stratification. Intermediate-risk cases, like low-risk cases, are at a lower risk of DSA and ABMR. This new way of risk evaluation may facilitate individualized immunosuppression and surveillance.</p