Islet autoimmunity identifies a unique pattern of impaired pancreatic beta-cell function, markedly reduced pancreatic beta cell mass and insulin resistance in clinically diagnosed type 2 diabetes

There is a paucity of literature describing metabolic and histological data in adult-onset autoimmune diabetes. This subgroup of diabetes mellitus affects at least 5% of clinically diagnosed type 2 diabetic patients (T2DM) and it is termed Latent Autoimmune Diabetes in Adults (LADA). We evaluated indexes of insulin secretion, metabolic assessment, and pancreatic pathology in clinically diagnosed T2DM patients with and without the presence of humoral islet autoimmunity (Ab). A total of 18 patients with at least 5-year duration of clinically diagnosed T2DM were evaluated in this study. In those subjects we assessed acute insulin responses to arginine, a glucose clamp study, whole-body fat mass and fat-free mass. We have also analyzed the pancreatic pathology of 15 T2DM and 43 control cadaveric donors, using pancreatic tissue obtained from all the T2DM organ donors available from the nPOD network through December 31, 2013. The presence of islet Ab correlated with severely impaired β-cell function as demonstrated by remarkably low acute insulin response to arginine (AIR) when compared to that of the Ab negative group. Glucose clamp studies indicated that both Ab positive and Ab negative patients exhibited peripheral insulin resistance in a similar fashion. Pathology data from T2DM donors with Ab or the autoimmune diabetes associated DR3/DR4 allelic class II combination showed reduction in beta cell mass as well as presence of autoimmune-associated pattern A pathology in subjects with either islet autoantibodies or the DR3/DR4 genotype. In conclusion, we provide compelling evidence indicating that islet Ab positive long-term T2DM patients exhibit profound impairment of insulin secretion as well as reduced beta cell mass seemingly determined by an immune-mediated injury of pancreatic β-cells. Deciphering the mechanisms underlying beta cell destruction in this subset of diabetic patients may lead to the development of novel immunologic therapies aimed at halting the disease progression in its early stage

Interplay Between Toxoplasma gondii, Autophagy, and Autophagy Proteins

Survival of Toxoplasma gondii within host cells depends on its ability of reside in a vacuole that avoids lysosomal degradation and enables parasite replication. The interplay between immune-mediated responses that lead to either autophagy-driven lysosomal degradation or disruption of the vacuole and the strategies used by the parasite to avoid these responses are major determinants of the outcome of infection. This article provides an overview of this interplay with an emphasis on autophagy

HIV-1 Inhibits Autophagy in Bystander Macrophage/Monocytic Cells through Src-Akt and STAT3

Autophagy is a homeostatic mechanism of lysosomal degradation. Defective autophagy has been linked to various disorders such as impaired control of pathogens and neurodegeneration. Autophagy is regulated by a complex array of signaling pathways that act upstream of autophagy proteins. Little is known about the role of altered regulatory signaling in disorders associated with defective autophagy. In particular, it is not known if pathogens inhibit autophagy by modulation of upstream regulatory pathways. Cells infected with HIV-1 blocked rapamycin-induced autophagy and CD40-induced autophagic killing of Toxoplasma gondii in bystander (non-HIV-1 infected) macrophage/monocytic cells. Blockade of autophagy was dependent on Src-Akt and STAT3 triggered by HIV-1 Tat and IL-10. Neutralization of the upstream receptors VEGFR, beta-integrin or CXCR4, as well as of HIV-1 Tat or IL-10 restored autophagy in macrophage/monocytic cells exposed to HIV-1-infected cells. Defective autophagic killing of T. gondii was detected in monocyte-derived macrophages from a subset of HIV-1(+) patients. This defect was also reverted by neutralization of Tat or IL-10. These studies revealed that a pathogen can impair autophagy in non-infected cells by activating counter-regulatory pathways. The fact that pharmacologic manipulation of cell signaling restored autophagy in cells exposed to HIV-1-infected cells raises the possibility of therapeutic manipulation of cell signaling to restore autophagy in HIV-1 infection

Recent Advances in the Roles of Autophagy and Autophagy Proteins in Host Cells During Toxoplasma gondii Infection and Potential Therapeutic Implications

Toxoplasma gondii is an obligate intracellular protozoan that can cause encephalitis and retinitis in humans. The success of T. gondii as a pathogen depends in part on its ability to form an intracellular niche (parasitophorous vacuole) that allows protection from lysosomal degradation and parasite replication. The parasitophorous vacuole can be targeted by autophagy or by autophagosome-independent processes triggered by autophagy proteins. However, T. gondii has developed many strategies to preserve the integrity of the parasitophorous vacuole. Here, we review the interaction between T. gondii, autophagy, and autophagy proteins and expand on recent advances in the field, including the importance of autophagy in the regulation of invasion of the brain and retina by the parasite. We discuss studies that have begun to explore the potential therapeutic applications of the knowledge gained thus far

Deconstructing the DGAT1 enzyme: membrane interactions at substrate binding sites

Diacylglycerol acyltransferase 1 (DGAT1) is a key enzyme in the triacylglyceride synthesis pathway. Bovine DGAT1 is an endoplasmic reticulum membrane-bound protein associated with the regulation of fat content in milk and meat. The aim of this study was to evaluate the interaction of DGAT1 peptides corresponding to putative substrate binding sites with different types of model membranes. Whilst these peptides are predicted to be located in an extramembranous loop of the membrane-bound protein, their hydrophobic substrates are membrane-bound molecules. In this study, peptides corresponding to the binding sites of the two substrates involved in the reaction were examined in the presence of model membranes in order to probe potential interactions between them that might influence the subsequent binding of the substrates. Whilst the conformation of one of the peptides changed upon binding several types of micelles regardless of their surface charge, suggesting binding to hydrophobic domains, the other peptide bound strongly to negatively-charged model membranes. This binding was accompanied by a change in conformation, and produced leakage of the liposome-entrapped dye calcein. The different hydrophobic and electrostatic interactions observed suggest the peptides may be involved in the interactions of the enzyme with membrane surfaces, facilitating access of the catalytic histidine to the triacylglycerol substrates

Impacto de las tecnologías de la información y comunicación en la dinámica familiar de estudiantes universitarios

Las TIC son relevantes para los estudiantes universitarios; por ello es importante conocer el impacto de estas en el contexto familiar. Se realizaron investigaciones del impacto de las TIC en la familia durante la pandemia del Covid-19; sin embargo, consideramos que es importante investigar la influencia de las TIC en la dinámica familiar desde la perspectiva del estudiante universitario de pregrado en la actualidad. El objetivo fue describir el uso de las TIC por parte de estudiantes universitarios y su influencia en la dinámica familiar. La muestra estuvo conformada por 67 estudiantes de pregrado. La investigación tuvo un enfoque descriptivo cuantitativo de carácter aplicado. Entre los principales resultados tenemos que el 73 % de los estudiantes consideran que la influencia de las TIC en la integración familiar es poco frecuente o nula, el 86,5 % opina que las TIC son útiles para comunicarse con la familia cuando están lejos de casa, y el 53,8 % menciona que a través de las redes sociales apenas se comunican con sus padres. Los estudiantes consideran que las TIC no influyen en la dinámica familiar porque según su percepción las TIC solo suelen usarlas, en el contexto familiar, para comunicar cosas puntuales, comunicarse cuando están lejos o realizar algún de actividad recreativa en familia.Information and Communication Technologies (ICT) are significant for university students; thus, it is necessary to understand the influence of these technologies on the family setting. Investigations were conducted on the impact of ICT on families during the Covid-19 pandemic; however, we believe it is vital to investigate the influence of ICT on the family dynamics from the perspective of undergraduate university students in the present time. The aim was to describe the utilization of ICT by university students and its impact on family dynamics. The sample consisted of 67 undergraduate students. The research has an applied quantitative descriptive approach. Among the main findings, 73% of students believe that the influence of ICT on family integration is infrequent or nonexistent, 86.5% believe that ICT is useful for communicating with family when they are away from home, and 53.8% mention that they barely communicate with their parents through social media. According to the students' perception, they believe that ICT does not influence family dynamics since they only tend to use ICT in the family setting for specific communication purposes, to stay in touch while they are apart, or to engage in recreational activities as a family

Aplicación de un programa de comprensión lectora inferencial en alumnos de una Escuela de Formación Técnica

Se plantea la investigación referida al nivel de comprensión lectora de estudiantes de una Escuela de Formación Técnica, para lo cual se elaboró y aplicó un programa de comprensión lectora denominado “La lectura estimula la imaginación”, el cual fue evaluado considerando la comparación respectiva entre el grupo control y el grupo experimental. La población de estudio estuvo conformada por 244 alumnos de una Escuela de Formación Técnica, los cuales tienen un promedio de edad entre 17 - 23 años. La comprensión lectora fue evaluada utilizando una prueba elaborada con la técnica cloze. Esta prueba consiste en una lectura, en la cual se ha subrayado tres palabras, a lo largo de cada línea del texto, de las cuales se deberá encerrar en un círculo la palabra correcta, que completará y dará sentido lógico a la lectura. El diseño utilizado correspondió a un diseño con grupo control y experimental pre y post test. Al efectuarse el análisis de los resultados, se halló que efectivamente existen diferencias significativas en el nivel de comprensión de lectura entre los que recibieron el programa de comprensión lectora y aquellos a quienes no se les aplicó el mencionado programa. De esta manera se comprobó que el mencionado programa de comprensión lectora inferencial es efectivo.Tesi

Neutrophil Extracellular Traps Go Viral

Neutrophils are the most numerous immune cells. Their importance as the first line of defense against bacterial and fungal pathogens is well described. In contrast, the role of neutrophils in controlling viral infections is less clear. Bacterial and fungal pathogens can stimulate neutrophils extracellular traps (NETs) in a process called NETosis. Although NETosis has previously been described as a special form of programmed cell death, there are forms of NET production that do not end with the demise of neutrophils. As an end result of NETosis, genomic DNA complexed with microbicidal proteins is expelled from neutrophils. These structures can kill pathogens or at least prevent their local spread within host tissue. On the other hand, disproportionate NET formation can cause local or systemic damage. Only recently, it was recognized that viruses can also induce NETosis. In this review, we discuss the mechanisms by which NETs are produced in the context of viral infection and how this may contribute to both antiviral immunity and immunopathology. Finally, we shed light on viral immune evasion mechanisms targeting NETs

Parasite fate and involvement of infected cells in the induction of CD4+ and CD8+ T cell responses to Toxoplasma gondii

During infection with the intracellular parasite Toxoplasma gondii, the presentation of parasite-derived antigens to CD4+ and CD8+ T cells is essential for long-term resistance to this pathogen. Fundamental questions remain regarding the roles of phagocytosis and active invasion in the events that lead to the processing and presentation of parasite antigens. To understand the most proximal events in this process, an attenuated non-replicating strain of T. gondii (the cpsII strain) was combined with a cytometry-based approach to distinguish active invasion from phagocytic uptake. In vivo studies revealed that T. gondii disproportionately infected dendritic cells and macrophages, and that infected dendritic cells and macrophages displayed an activated phenotype characterized by enhanced levels of CD86 compared to cells that had phagocytosed the parasite, thus suggesting a role for these cells in priming naïve T cells. Indeed, dendritic cells were required for optimal CD4+ and CD8+ T cell responses, and the phagocytosis of heat-killed or invasion-blocked parasites was not sufficient to induce T cell responses. Rather, the selective transfer of cpsII-infected dendritic cells or macrophages (but not those that had phagocytosed the parasite) to naïve mice potently induced CD4+ and CD8+ T cell responses, and conferred protection against challenge with virulent T. gondii. Collectively, these results point toward a critical role for actively infected host cells in initiating T. gondii-specific CD4+ and CD8+ T cell responses

La formalización en las micro y pequeñas empresas del sector servicio – rubro mototaxis del distrito de san Vicente, provincia de Cañete, departamento de Lima, período 2015

La investigación tuvo como objetivo general, determinar las principales características de la formalización en las micro y pequeñas empresas del sector servicio – rubro mototaxis, del distrito de San Vicente, provincia de Cañete, departamento de Lima, período 2015. La investigación fue cuantitativa – descriptiva y el recojo de información estuvo dirigida a una muestra de 11 MYPE en el rubro mototaxis del distrito de San Vicente, a quienes se les aplicó un cuestionario de preguntas cerradas, mediante la técnica de la encuesta. En la encuesta realizada se obtuvieron los siguientes resultados: el 72.7% de la población encuestada son empresas formales, las mismas que aseguran que el gran beneficio de ser formal es tener acceso a créditos, mientras un 18.2% mencionan que una empresa formal genera confianza, mientras un 9,1% indican que ser una empresa formal les generará tener un mayor volumen de ventas. Otro de los puntos importantes que se pudo observar en las MYPE, es que el 72.7% tuvieron regularmente problemas para formalizar su empresa, aducen que existen barreras burocráticas y esto hace que los tramites sean más engorrosos; mientras un 27,3% de las MYPE mencionan que tuvieron muchos problemas para formalizar su empresa. Finalmente, las conclusiones obtenidas en dicha investigación son: que las MYPE rubro - mototaxi del distrito de San Vicente, se encuentran formalizadas y consideran importante el acceso a créditos que obtienen, beneficiándolos en su vida familiar y empresarialTesi