201 research outputs found

    Hábitos de estudio y aprendizaje autorregulado en estudiantes universitarios

    Get PDF
    The general objective of this research was to determine if there is a relationship between the variables study habits and self-regulated learning. The study design was a non-experimental cross-sectional correlational scope. The sample consisted of 90 students, out of a total of 280 students from the VIII cycle of the international business and administration career at a private university in Lima. The instruments used were questionnaires A and B. Once the results had been analyzed, it was evident that, for the sample of this study, between the variables study habits and self-regulated learning there is a significant positive statistical correlation of p <.05 and rho of Sperman of ρ = 0.890 **.La presente investigación tuvo como objetivo general determinar si existe relación entre las variables hábitos de estudio y aprendizaje autorregulado. El diseño de estudio fue no experimental transversal de alcance correlacional. La muestra estuvo integrada por 90 estudiantes, de un total de 280 estudiantes del VIII ciclo de la carrera de administración y negocios internacionales de una universidad privada de Lima. Los instrumentos utilizados fueron los cuestionarios A y B. Una vez analizados los resultados, se pudo evidenciar que, para la muestra de este estudio, entre las variables hábitos de estudio y aprendizaje autorregulado existe correlación estadística positiva significativa de p < .05 y rho de Sperman de ρ = 0.890**

    Modeling of the luminal butyrate concentration to design an oral formulation capable of achieving a pharmaceutical response

    Get PDF
    Butyrate concentrations required for a direct effect on intestinal epithelial cells lie between 2–5 mM. In order for butyrate to affect the small intestine the local pharmacokinetics need to be understood. We used a mathematical approach to model the luminal butyrate concentration after oral administration of an immediate release formulation or a sustained release formulation to humans. This model was used to design an oral formulation capable of achieving a local pharmaceutical response in the small intestine. The model showed that an immediate release formulation is only capable of maintaining pharmacologically active concentrations during the first half hour after the formulation has entered the small intestine. A sustained release formulation is capable of maintaining pharmacologically active concentrations for hours and thus throughout the whole small intestine. To reach these concentrations the sustained release formulation requires a zero order release rate of 0.08-0.2 mmol/h. The anticipated release rates are expected to result in luminal butyrate concentrations that are high enough at the surface of the epithelial cells to improve the intestinal barrier and to have anti-inflammatory properties. However, it is uncertain if the duration of exposure, and quantity of exposed epithelial cells is adequate to have a clinical effect

    Nanopore Sequencing Enables Comprehensive Transposable Element Epigenomic Profiling

    Get PDF
    Transposable elements (TEs) drive genome evolution and are a notable source of pathogenesis, including cancer. While CpG methylation regulates TE activity, the locus-specific methylation landscape of mobile human TEs has to date proven largely inaccessible. Here, we apply new computational tools and long-read nanopore sequencing to directly infer CpG methylation of novel and extant TE insertions in hippocampus, heart, and liver, as well as paired tumor and non-tumor liver. As opposed to an indiscriminate stochastic process, we find pronounced demethylation of young long interspersed element 1 (LINE-1) retrotransposons in cancer, often distinct to the adjacent genome and other TEs. SINE-VNTR-Alu\ua0(SVA) retrotransposons, including their internal tandem repeat-associated CpG island, are near-universally methylated. We encounter allele-specific TE methylation and demethylation of aberrantly expressed young LINE-1s in normal tissues. Finally, we recover the complete sequences of tumor-specific LINE-1 insertions and their retrotransposition hallmarks, demonstrating how long-read sequencing can simultaneously survey the epigenome and detect somatic TE mobilization

    Patient coaching in secondary care:healthcare professionals' views on target group, intervention and coach profile

    Get PDF
    Background: Not all patients are able to communicate effectively during consultations with medical specialists. Patient coaching has shown to be effective for enhancing communication. Objective: We aimed to get healthcare professionals' views on target groups for patient coaching, on supportive elements in patient coaching and on the necessary qualifications and profile of a patient coach, to further our knowledge on the concept of patient coaching as supportive intervention for patients in consultations with medical specialists. Methods: We chose a qualitative research design and interviewed 18 healthcare professionals (six medical specialists, four family physicians, four community nurses and four nurse specialists/physician assistants) and analysed the verbatim transcripts using Qualitative Analysis Guide of Leuven. After a short introduction of the global concept of patient coaching and presentation of patients' perceived barriers, two interviewers structured the interview around three research questions: which patients could benefit from a patient coach, what should such a coach do and who could act like such a coach? Results: Participants describe patients who could benefit from patient coaching as generally vulnerable (e.g. older age, insufficiently accompanied, lower socioeconomic status, co-morbidity and cognitive problems) but also patients who are situationally vulnerable (e.g. elicited by bad news). Patient coaching should comprise emotional and instrumental support, aiming at reducing stress and improving the processing of medical information. Patient coaching should start from the patient's home and include preparing questions, navigating to and in the hospital, recording information during the consultation, checking understanding and recalling information. Patient coaches should have at least basic medical knowledge and a higher education. Conclusion: Healthcare professionals believe that patient coaching by a trained professional with medical knowledge could be beneficial to patients who are stressed when visiting a medical specialist. Future research should involve the views of patients on patient coaching, focus on investigating to what extent patient coaching is able to reduce stress and support a patient in processing medical information and the preferred patient coach's profile

    Helicobacter pylori Modulates the T Helper Cell 1/T Helper Cell 2 Balance through Phase-variable Interaction between Lipopolysaccharide and DC-SIGN

    Get PDF
    The human gastric pathogen Helicobacter pylori spontaneously switches lipopolysaccharide (LPS) Lewis (Le) antigens on and off (phase-variable expression), but the biological significance of this is unclear. Here, we report that Le+ H. pylori variants are able to bind to the C-type lectin DC-SIGN and present on gastric dendritic cells (DCs), and demonstrate that this interaction blocks T helper cell (Th)1 development. In contrast, Le− variants escape binding to DCs and induce a strong Th1 cell response. In addition, in gastric biopsies challenged ex vivo with Le+ variants that bind DC-SIGN, interleukin 6 production is decreased, indicative of increased immune suppression. Our data indicate a role for LPS phase variation and Le antigen expression by H. pylori in suppressing immune responses through DC-SIGN

    Targeting self- and foreign antigens to dendritic cells via DC-ASGPR generates IL-10-producing suppressive CD4+ T cells

    Get PDF
    Dendritic cells (DCs) can initiate and shape host immune responses toward either immunity or tolerance by their effects on antigen-specific CD4(+) T cells. DC-asialoglycoprotein receptor (DC-ASGPR), a lectinlike receptor, is a known scavenger receptor. Here, we report that targeting antigens to human DCs via DC-ASGPR, but not lectin-like oxidized-LDL receptor, Dectin-1, or DC-specific ICAM-3-grabbing nonintegrin favors the generation of antigen-specific suppressive CD4(+) T cells that produce interleukin 10 (IL-10). These findings apply to both self-and foreign antigens, as well as memory and naive CD4(+) T cells. The generation of such IL-10-producing CD4(+) T cells requires p38/extracellular signal-regulated kinase phosphorylation and IL-10 induction in DCs. We further demonstrate that immunization of nonhuman primates with antigens fused to anti-DC-ASGPR monoclonal antibody generates antigen-specific CD4(+) T cells that produce IL-10 in vivo. This study provides a new strategy for the establishment of antigen-specific IL-10-producing suppressive T cells in vivo by targeting whole protein antigens to DCs via DC-ASGPR

    Identity Determinants of the Translocation Signal for a Type 1 Secretion System

    Get PDF
    The toxin hemolysin A was first identified in uropathogenic E. coli strains and shown to be secreted in a one-step mechanism by a dedicated secretion machinery. This machinery, which belongs to the Type I secretion system family of the Gram-negative bacteria, is composed of the outer membrane protein TolC, the membrane fusion protein HlyD and the ABC transporter HlyB. The N-terminal domain of HlyA represents the toxin which is followed by a RTX (Repeats in Toxins) domain harboring nonapeptide repeat sequences and the secretion signal at the extreme C-terminus. This secretion signal, which is necessary and sufficient for secretion, does not appear to require a defined sequence, and the nature of the encoded signal remains unknown. Here, we have combined structure prediction based on the AlphaFold algorithm together with functional and in silico data to examine the role of secondary structure in secretion. Based on the presented data, a C-terminal, amphipathic helix is proposed between residues 975 and 987 that plays an essential role in the early steps of the secretion process.</jats:p

    Analysis of Stochastic Strategies in Bacterial Competence: A Master Equation Approach

    Get PDF
    Competence is a transiently differentiated state that certain bacterial cells reach when faced with a stressful environment. Entrance into competence can be attributed to the excitability of the dynamics governing the genetic circuit that regulates this cellular behavior. Like many biological behaviors, entrance into competence is a stochastic event. In this case cellular noise is responsible for driving the cell from a vegetative state into competence and back. In this work we present a novel numerical method for the analysis of stochastic biochemical events and use it to study the excitable dynamics responsible for competence in Bacillus subtilis. Starting with a Finite State Projection (FSP) solution of the chemical master equation (CME), we develop efficient numerical tools for accurately computing competence probability. Additionally, we propose a new approach for the sensitivity analysis of stochastic events and utilize it to elucidate the robustness properties of the competence regulatory genetic circuit. We also propose and implement a numerical method to calculate the expected time it takes a cell to return from competence. Although this study is focused on an example of cell-differentiation in Bacillus subtilis, our approach can be applied to a wide range of stochastic phenomena in biological systems

    SMPD4 regulates mitotic nuclear envelope dynamics and its loss causes microcephaly and diabetes

    Get PDF
    Biallelic loss-of-function variants in SMPD4 cause a rare and severe neurodevelopmental disorder with progressive congenital microcephaly and early death. SMPD4 encodes a sphingomyelinase that hydrolyses sphingomyelin into ceramide at neutral pH and can thereby affect membrane lipid homeostasis. SMPD4 localizes to the membranes of the endoplasmic reticulum and nuclear envelope and interacts with nuclear pore complexes (NPC). We refine the clinical phenotype of loss-of-function SMPD4 variants by describing five individuals from three unrelated families with longitudinal data due to prolonged survival. All individuals surviving beyond infancy developed insulin-dependent diabetes, besides presenting with a severe neurodevelopmental disorder and microcephaly, making diabetes one of the most frequent age-dependent non-cerebral abnormalities. We studied the function of SMPD4 at the cellular and organ levels. Knock-down of SMPD4 in human neural stem cells causes reduced proliferation rates and prolonged mitosis. Moreover, SMPD4 depletion results in abnormal nuclear envelope breakdown and reassembly during mitosis and decreased post-mitotic NPC insertion. Fibroblasts from affected individuals show deficient SMPD4-specific neutral sphingomyelinase activity, without changing (sub)cellular lipidome fractions, which suggests a local function of SMPD4 on the nuclear envelope. In embryonic mouse brain, knockdown of Smpd4 impairs cortical progenitor proliferation and induces premature differentiation by altering the balance between neurogenic and proliferative progenitor cell divisions. We hypothesize that, in individuals with SMPD4-related disease, nuclear envelope bending, which is needed to insert NPCs in the nuclear envelope, is impaired in the absence of SMPD4 and interferes with cerebral corticogenesis and survival of pancreatic beta cells.</p
    corecore