Using an extracurricular Honors program to engage future physician into scientific research in early stages of medical training

Physician-scientists are urgently needed to make progress in the dynamic world of medical healthcare. Currently, there is a worldwide shortage in physicians pursuing a scientific career. Actively engaging students in research in early stages of medical training could help to direct students towards a scientific career and contribute to creating the next generation of physicianscientists. Leiden University Medical Center (LUMC) implemented an extracurricular Honors program with a fundamental orientation towards research. The program starts in the second year of medical training and is comprised of four different tracks in order to attract multiple types of students with different interests. All four tracks offer students scholarly experiences, but differ in content and amount of provided structure. The LUMC Honors program has a clear goal to develop future physician-scientists, and combined with its unique multiple-track model, the program accommodates about 70 students (25%) each year. The number of students in the program has grown and students’ experiences are positive.Stemcel biology/Regenerative medicine (incl. bloodtransfusion

Usage of TCRAV and TCRBV gene families in human fetal and adult TCR rearrangements

We have investigated fetal and adult T-cell receptor (TCR) A and B V-gene repertoires both by fluorescence-activated cell sorter (FACS) analysis with the avialable TCR V region-specific mAbs and by the polymerase chain reaction (PRC) with TRC V gene family-specific oligonucleotides. Among the low number of CD3+ T cells, most of the TRC V region tested for could be detected by FACS analysis in liver, bone marrow, and spleen derived from a 14-week-old fetus and two 15-weeks-old fetuses. Similarly, the PCR analysis showed that the majority of the TCRAV and TCRBV families were expressed in the peripheral organs of the 13-week-old fetus, although an apparent absence of particular TCR V families was found in liver and bone marrow. This was most probably the consequence of the low number of CD3+ T cells in these organs. In 17-week-old week-old fetal thymi the level of expression of some TCRAV and TCRBV gene families, in particular those that contain single member, was lower compared to post-partum thymi and adult peripheral blood mononuclear cells. The combined data of FACS and PCR analysis demonstrate that TCR genes belonging to the majority of TCR V gene families can be used in TCR α and β chain rearrngements during early human fetal life. Our data also suggest that the expression levels of some of the single member TCR V gene families may be influenced by the development stage

Bringing antigens to attention: a conspiracy of genes, proteins and cells

Stemcel biology/Regenerative medicine (incl. bloodtransfusion

NLRC5: a key regulator of MHC class I-dependent immune responses

Stemcel biology/Regenerative medicine (incl. bloodtransfusion

Alterations in cord blood leukocyte subsets of patients with severe hemolytic disease after intrauterine transfusion therapy

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Epigenetic control in immune function

This chapter describes recent advances in our understanding how epigenetic events control immune functions with emphasis on transcriptional regulation of major histocompatibility complex ClassI (MIC-I) and Class II (MHC-II) genes. MHC-I and MHC-II molecules play an essential role in the adaptive immune response by virtue of their ability to present peptides, respectively to CD8+ and CD4+ T cells. Central to the onset of an adequate immune response to pathogens is the presentation of pathogen-derived peptides in the context of MHC-II molecules by antigen presenting cells (APCs) to CD4+ T cells of the immune system. In particular dendritic cells are highly specialized APCs that are capable to activate naïve T cells. Given their central role in adaptive immunity, MHC-I and MHC-II genes are regulated in a tight fashion at the transcriptional level to meet with local requirements of an effective antigen-specific immune response. In these regulatory processes the MHC2TA encoded Class II transactivator (CIITA) plays a crucial role. CIITA is essential for transcriptional activation of all MHC-I genes, whereas it plays an ancillary function in the transcriptional control of MHC-I genes. The focus of this chapter therefore will be on the transcription factors that interact with conserved cis-acting promoter elements and epigenetic mechanisms that modulate cell type-specific regulation of MHC-I, MHC-I, and MHC2TA genes. Furthermore, we will also briefly discuss how genetic and epigenetic mechanisms contribute to T helper cell differentiation.Stemcel biology/Regenerative medicine (incl. bloodtransfusion

Skewing of TCRV-genes to the CD4+ and CD8+ subset of T-lymphocytes is not determined by amino acid composition of complementarity determining region 3

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