Expression Regulation of Major Histocompatibility Complex Class I and Class II Encoding Genes

Major histocompatibility complex (MHC)-I and MHC-II molecules play an essential role in the immune response to pathogens by virtue of their ability to present peptides to CD8+ and CD4+ T cells, respectively. Given this critical role, MHC-I and MHC-II genes are regulated in a tight fashion at the transcriptional level by a variety of transcription factors that interact with conserved cis-acting regulatory promoter elements. In addition to the activities of these regulatory factors, modification of chromatin also plays an essential role in the efficient transcription of these genes to meet with local requirement for an effective immune response. The focus of this review is on the transcription factors that interact with conserved cis-acting promoter elements and the epigenetic mechanisms that modulate induced and constitutive expression of these MHC genes

Age and sustainable labour participation: studying moderating effects

Purpose: Research findings are ambiguous regarding the effects of age on sustainable labour participation (SLP), defined as the extent to which people are able and willing to conduct their current and future work. The purpose of this paper is to contribute by examining age effects on SLP by focusing on the moderating role of workload. Design/methodology/approach: A mixed-method study was conducted in 2018. First, a survey was distributed among a sample of 2,149 employees of the Dutch central government. Second, 12 interviews with public sector employees took place to gain greater insight into the quantitative data collected. Findings: Three components that reflect an employee’s SLP were studied: vitality, work ability and employability. The quantitative results, in general, showed that SLP decreased with ageing. However, in contrast to the hypothesis, the results showed a significant positive relationship between age and energy. Moreover, relationships between an employee’s age and certain aspects of their SLP were moderated by workload. The interviews helped to interpret these results. Practical implications: The findings demonstrate that some of the older worker stereotypes are unfounded, and the important practical implications of these are discussed. Originality/value: Earlier research has produced conflicting findings regarding the relationship between age and (aspects of) SLP. By investigating several aspects of SLP in separate regressions within this research, the specific influences of age have become clearer. Furthermore, the research provides fresh insights into the relationship between age and SLP by including moderating effects of workload

Site α Is Crucial for Two Routes of IFNγ-Induced MHC Class I Transactivation: The ISRE-Mediated Route and a Novel Pathway Involving CIITA

AbstractThe constitutive and cytokine-induced levels of major histocompatibility (MHC) class I expression are tightly controlled at the transcriptional level. In this study, it is shown that the cis-acting regulatory element site α of the MHC class I promoter is essential for the IFNγ-induced transactivation of MHC class I gene expression through the ISRE. Moreover, it was discovered that the class II transactivator (CIITA), which is itself under the control of the IFNγ induction pathway, strongly transactivates MHC class I gene expression and exerts its activity through site α. Therefore, site α is a crucial regulatory element, mediating the classic route of IFNγ induction via the ISRE as well as a novel route of MHC class I transactivation involving CIITA

Оценка фискальной иллюзии при налогообложении доходов физических лиц

Фискальная иллюзия сама по себе не является негативным явлением, она всего лишь следствие осуществляемой фискальной политики государства. Тем не менее, фискальная иллюзия нарушает представление экономических агентов о масштабах государственного влияния в перераспределении своих доходов и тем самым способствует принятию ими не самых эффективных экономических решений.Фіскальна ілюзія сама по собі не є негативним явищем, вона всього лише слідство здійснюваної фіскальної політики держави. Проте, фіскальна ілюзія порушує уявлення економічних агентів про масштаби державного впливу в перерозподілі своїх доходів і тим самим сприяє ухваленню ними не найефективніших економічних рішень

Structural analysis of Salmonella enterica effector protein SopD

Salmonella outer protein D (SopD) is a type III secreted virulence effector protein from Salmonella enterica. Full-length SopD and SopD lacking 16 amino acids at the N-terminus (SopDDeltaN) have been expressed as fusions with GST in Escherichia coli, purified with a typical yield of 20-30 mg per litre of cell culture and crystallized. Biophysical characterization has been carried out mainly on SopDDeltaN. Analytical size exclusion chromatography shows that SopDDeltaN is monomeric and probably globular in aqueous solution. The secondary structure composition, calculated from the CD spectrum, is mixed (38% alpha-helix and 26% beta-strand). Sequence analysis indicates that SopD contains a coiled coil motif, as found in numerous other type III secretion system-associated proteins. This suggests that SopD has the potential for one or more heterotypic protein-protein interactions. Limited trypsin digestion of SopDDeltaN, monitored by both one-dimensional proton NMR spectroscopy and SDS-PAGE, shows that the protein has a large, protease-resistant core domain of 286 amino acid residues. This single-domain architecture suggests that SopD lacks a cognate chaperone. In crystallization trials, SopDDeltaN produced better crystals than either full-length SopD or trypsin-digested SopDDeltaN. Diffraction to 3.0 Angstrom resolution has so far been obtained from crystals of SopDDeltaN

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

Shaping the Gut Microbiota by Breastfeeding: The Gateway to Allergy Prevention?

Evidence is accumulating that demonstrates the importance of the gut microbiota in health and diseases such as allergy. Recent studies emphasize the importance of the “window of opportunity” in early life, during which interventions altering the gut microbiota induce long-term effects. The neonate's gut microbiota composition and metabolism could therefore play an essential role in allergic disease risk. Breastfeeding shapes the gut microbiota in early life, both directly by exposure of the neonate to the milk microbiota and indirectly, via maternal milk factors that affect bacterial growth and metabolism such as human milk oligosaccharides, secretory IgA, and anti-microbial factors. The potential of breastmilk to modulate the offspring's early gut microbiota is a promising tool for allergy prevention. Here, we will review the existing evidence demonstrating the impact of breastfeeding on shaping the neonate's gut microbiota and highlight the potential of this strategy for allergy prevention