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

Arabidopsis heterotrimeric G-protein regulates cell wall defense and resistance to necrotrophic fungi

The Arabidopsis heterotrimeric G-protein controls defense responses to necrotrophic and vascular fungi. The agb1 mutant impaired in the Gβ subunit displays enhanced susceptibility to these pathogens. Gβ/AGB1 forms an obligate dimer with either one of the Arabidopsis Gγ subunits (γ1/AGG1 and γ2/AGG2). Accordingly, we now demonstrate that the agg1 agg2 double mutant is as susceptible as agb1 plants to the necrotrophic fungus Plectosphaerella cucumerina. To elucidate the molecular basis of heterotrimeric G-protein-mediated resistance, we performed a comparative transcriptomic analysis of agb1-1 mutant and wild-type plants upon inoculation with P. cucumerina. This analysis, together with metabolomic studies, demonstrated that G-protein-mediated resistance was independent of defensive pathways required for resistance to necrotrophic fungi, such as the salicylic acid, jasmonic acid, ethylene, abscisic acid, and tryptophan-derived metabolites signaling, as these pathways were not impaired in agb1 and agg1 agg2 mutants. Notably, many mis-regulated genes in agb1 plants were related with cell wall functions, which was also the case in agg1 agg2 mutant. Biochemical analyses and Fourier Transform InfraRed (FTIR) spectroscopy of cell walls from G-protein mutants revealed that the xylose content was lower in agb1 and agg1 agg2 mutants than in wild-type plants, and that mutant walls had similar FTIR spectratypes, which differed from that of wild-type plants. The data presented here suggest a canonical functionality of the Gβ and Gγ1/γ2 subunits in the control of Arabidopsis immune responses and the regulation of cell wall composition

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

Contatexts: cómo interpretar textos contables en inglés

La presente investigación busca proveer al nuevo profesional de herramientas de acceso a la información y al conocimiento en un contexto de constante cambio y actualización. Para ello, a partir del análisis de material auténtico del área contable en Inglés, se diseñaron textos didactizados que fomentan la adquisición de competencias y del uso de estrategias correctas en lo que respecta a la lectura de una lengua extranjera para aplicarlos a textos académico-profesionales factibles de ser utilizados en la vida profesional y así poder enfrentar con autonomía los desafíos que surgen a partir de los procesos de transformación de las sociedades y los roles que los nuevos profesionales deberán asumir. Para ello, resultó imprescindible identificar las necesidades y recursos propios del área de incumbencia, proveer técnicas y estrategias de interpretación de textos inherentes y evaluar la efectividad de las secuencias propuestas.Fil: Marrari, Andrea F. Universidad Nacional de La Matanza; Argentina.Fil: Prado, Andrea P. Universidad Nacional de La Matanza; Argentina.Fil: Sanjurjo, Mariana. Universidad Nacional de La Matanza; Argentina

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

In Vitro Insights into the Dietary Role of Glucoraphanin and Its Metabolite Sulforaphane in Celiac Disease

Sulforaphane is considered the bioactive metabolite of glucoraphanin after dietary consumption of broccoli sprouts. Although both molecules pass through the gut lumen to the large intestine in stable form, their biological impact on the first intestinal tract is poorly described. In celiac patients, the function of the small intestine is affected by celiac disease (CD), whose severe outcomes are controlled by gluten-free dietary protocols. Nevertheless, pathological signs of inflammation and oxidative stress may persist. The aim of this study was to compare the biological activity of sulforaphane with its precursor glucoraphanin in a cellular model of gliadin-induced inflammation. Human intestinal epithelial cells (CaCo-2) were stimulated with a pro-inflammatory combination of cytokines (IFN-γ, IL-1β) and in-vitro-digested gliadin, while oxidative stress was induced by H2O2. LC-MS/MS analysis confirmed that sulforaphane from broccoli sprouts was stable after simulated gastrointestinal digestion. It inhibited the release of all chemokines selected as inflammatory read-outs, with a more potent effect against MCP-1 (IC50 = 7.81 μM). On the contrary, glucoraphanin (50 μM) was inactive. The molecules were unable to counteract the oxidative damage to DNA (γ-H2AX) and catalase levels; however, the activity of NF-κB and Nrf-2 was modulated by both molecules. The impact on epithelial permeability (TEER) was also evaluated in a Transwell® model. In the context of a pro-inflammatory combination including gliadin, TEER values were recovered by neither sulforaphane nor glucoraphanin. Conversely, in the context of co-culture with activated macrophages (THP-1), sulforaphane inhibited the release of MCP-1 (IC50 = 20.60 μM) and IL-1β (IC50 = 1.50 μM) only, but both molecules restored epithelial integrity at 50 μM. Our work suggests that glucoraphanin should not merely be considered as just an inert precursor at the small intestine level, thus suggesting a potential interest in the framework of CD. Its biological activity might imply, at least in part, molecular mechanisms different from sulforaphane

NTRK rearranged sarcoma of the bone. Role for larotrectinib in the neoadjuvant setting of an ultra-rare tumor: a case report

Background: Neurotrophic tyrosine receptor kinase (NTRK) gene-fusion targeted molecules revolutionized the paradigm of treatment of a limited subgroup of cancers of various histologies. Entrectinib and larotrectinib obtained unprecedented response rates in patients with cancer harboring NTRK rearrangements. This evidence recently led to the agnostic approval of these drugs, and evidence (confirmation) of their activity in a broader disease setting is emerging. Here, we report the case of a patient affected by EML4-NTRK3 rearranged undifferentiated spindle cell bone sarcoma treated with larotrectinib, and we argue (discuss about) the incidence and clinical presentation of NTRK gene-fusion positive bone sarcomas, the potential use of upfront treatment with NTRK inhibitors in neoadjuvant setting, and the role of a multidisciplinary tumor board. Despite the rarity of these rearrangements in patients with primitive bone sarcomas, the therapy with NTRK inhibitors represents a highly effective strategy to be pursued in selected cases even in neoadjuvant settings. The management of these very rare cancers should always be discussed in a multidisciplinary board of reference centers

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