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1.
Ann Anat ; 217: 60-65, 2018 May.
Article in English | MEDLINE | ID: mdl-29501634

ABSTRACT

Gaining sufficient knowledge of anatomy is an important part of medical education. Factors that influence how well students learn anatomical structures include available sources, learning time and study assistance. This study explores the attitude of medical students with regard to studying anatomy and evaluates possibilities for improvement of training in anatomy. Twenty medical students participated in a focus group meeting. Based on this focus group, an online survey consisting of 27 questions was developed and distributed amongst medical students of Maastricht University, the Netherlands. A total of 495 medical students (both Bachelor and Master level) participated in this survey. Master students found studying anatomy less attractive than Bachelor students (36.8% of the Master students vs. 47.9% of the Bachelor students (p=.024)). Although most students responded that they thought it is important to study anatomy, 48% of all students studied anatomy less than 10h per study block of 8 weeks. Only 47.9% of the students rated their knowledge of anatomy as adequate. Students suggested that three-dimensional techniques would help improve their knowledge of anatomy. Therefore investing in three-dimensional tools could prove beneficial in the future.


Subject(s)
Anatomy/education , Students, Medical , Adolescent , Adult , Attitude of Health Personnel , Audiovisual Aids , Cross-Sectional Studies , Curriculum , Education, Medical, Undergraduate , Educational Measurement , Female , Focus Groups , Humans , Learning , Male , Young Adult
2.
Int J Obes (Lond) ; 40(3): 507-13, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26471343

ABSTRACT

BACKGROUND/OBJECTIVES: Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are key enzymes involved in intracellular lipid catabolism. We have previously shown decreased expression and activity of these lipases in adipose tissue of obese insulin resistant individuals. Here we hypothesized that lipase deficiency might impact on insulin sensitivity and metabolic homeostasis in adipocytes not just by enhancing lipid accumulation, but also by altering lipid and carbohydrate catabolism in a peroxisome proliferator-activated nuclear receptor (PPAR)-dependent manner. METHODS: To address our hypothesis, we performed a series of in vitro experiments in a human white adipocyte model, the human multipotent adipose-derived stem (hMADS) cells, using genetic (siRNA) and pharmacological knockdown of ATGL and/or HSL. RESULTS: We show that ATGL and HSL knockdown in hMADS adipocytes disrupted mitochondrial respiration, which was accompanied by a decreased oxidative phosphorylation (OxPhos) protein content. This lead to a reduced exogenous and endogenous palmitate oxidation following ATGL knockdown, but not in HSL deficient adipocytes. ATGL deficiency was followed by excessive triacylglycerol accumulation, and HSL deficiency further increased diacylglycerol accumulation. Both single and double lipase knockdown reduced insulin-stimulated glucose uptake, which was attributable to impaired insulin signaling. These effects were accompanied by impaired activation of the nuclear receptor PPARα, and restored on PPARα agonist treatment. CONCLUSIONS: The present study indicates that lipase deficiency in human white adipocytes contributes to mitochondrial dysfunction and insulin resistance, in a PPARα-dependent manner. Therefore, modulation of adipose tissue lipases may provide a promising strategy to reverse insulin resistance in obese and type 2 diabetic patients.


Subject(s)
Adipocytes, White/metabolism , Adiposity/physiology , Insulin Resistance/physiology , Lipase/deficiency , Mitochondria/metabolism , Obesity/metabolism , PPAR alpha/agonists , Cells, Cultured , Energy Metabolism , Humans , Lipase/physiology , Lipolysis/physiology , Obesity/complications , Sterol Esterase/metabolism
3.
Tissue Antigens ; 85(4): 242-51, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25735891

ABSTRACT

Human Leukocyte Antigen (HLA)-E is a low-polymorphic non-classical HLA class I molecule which plays a crucial role in immune surveillance by presentation of peptides to T and natural killer (NK) cells. HLA-E polymorphism is related to HLA-E surface expression and is associated with patient outcome after stem cell transplantation. We aim to investigate the regulation of HLA-E expression level in peripheral blood mononuclear cells (PBMCs) of healthy individuals homozygous for HLA-E*01:01 or HLA-E*01:03, by using a panel of HLA-E binding peptides derived from CMV, Hsp60 and HLA class I. Basal and peptide-induced HLA-E surface expression levels were higher in PBMC from HLA-E*01:03 homozygous subjects as compared to PBMC from HLA-E*01:01 homozygous subjects. HLA-E mRNA levels were comparable between the two genotypes and remained constant after peptide stimulation. HLA-E surface expression seemed to be not only dependent on the HLA-E genotype, but also on the sequence of the peptide as evidenced by the profound difference in HLA-E upregulation with the Hsp60 and the B7 peptide. Our results showed that peptide-induced HLA-E expression is regulated at the posttranscriptional level as extracellular peptide stimulation did not influence RNA expression. This study provides new insights in the mechanism by which HLA-E expression is regulated and underlines a new role for extracellular peptides in inducing HLA-E translation, which may represent a defense mechanism against lytic viral infections and necrosis.


Subject(s)
Histocompatibility Antigens Class I/genetics , Leukocytes, Mononuclear/drug effects , Peptides/pharmacology , RNA, Messenger/genetics , Amino Acid Sequence , Chaperonin 60/chemistry , Chaperonin 60/immunology , Cytomegalovirus/chemistry , Cytomegalovirus/immunology , Cytotoxicity, Immunologic , Gene Expression Regulation , Genotype , HLA-B Antigens/chemistry , HLA-B Antigens/immunology , HLA-C Antigens/chemistry , HLA-C Antigens/immunology , Histocompatibility Antigens Class I/immunology , Homozygote , Humans , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/immunology , Mitochondrial Proteins/chemistry , Mitochondrial Proteins/immunology , Molecular Sequence Data , Peptides/chemistry , Peptides/immunology , Primary Cell Culture , RNA, Messenger/immunology , Signal Transduction , Structure-Activity Relationship , HLA-E Antigens
4.
Int J Obes (Lond) ; 32(7): 1076-82, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18427563

ABSTRACT

The prevalence of obesity and related metabolic disorders increases rapidly in western societies. A proper choice of foods may now prevent or delay many of the health consequences related to these disorders. In this respect, replacing dietary saturated fatty acids (SFAs) by cis-monounsaturated fatty acids (cis-MUFAs) has beneficial effects. In addition to diet-derived cis-MUFAs, the human body can also generate cis-MUFAsfrom SFAs through the action of stearoyl-CoA desaturases (SCDs). SCDs may play an adverse role in obesity and obesity-related insulin resistance. Here, we review the current knowledge on the molecular aspects and the role of SCD1 in obesity and the metabolic syndrome (MS). In mice, many studies have suggested a negative role for SCD1 in the development of obesity and insulin resistance. In humans, however, evidence is less convincing. If anything, increased, rather than decreased, levels of SCD1 mRNA levels are negatively associated with MS-related diseases such as insulin resistance. However, an unequivocal conclusion is currently not possible as the number of human studies is limited. Therefore, more human studies are needed at the molecular as well as at the physiological level to understand the true role of SCD1 during the development of obesity and the MS.


Subject(s)
Gene Expression Regulation , Metabolic Syndrome/enzymology , Obesity/enzymology , Stearoyl-CoA Desaturase/physiology , Animals , Humans , Membrane Fluidity , Mice , Models, Animal , Neoplasms/complications , Neoplasms/enzymology , Obesity/complications
5.
Physiol Behav ; 94(2): 187-97, 2008 May 23.
Article in English | MEDLINE | ID: mdl-18191967

ABSTRACT

The prevalence of the metabolic syndrome is rapidly increasing. This syndrome is characterized by metabolic disturbances, such as abnormal lipid and carbohydrate metabolism and a low-grade inflammatory state. PPARs play an important role in these metabolic processes, which makes them effective targets for treatment and prevention of the metabolic syndrome. Synthetic PPAR agonists, such as fibrates and thiazolidinediones are already used to treat hyperlipidemia and diabetes mellitus, respectively. Besides synthetic ligands, dietary fatty acids and fatty acid derivatives can also bind to an activate PPARs. As demonstrated with ligand-binding assays, PPARs have a clear preference of binding polyunsaturated fatty acids. Monounsaturated fatty acids are also very effective in binding PPARs, whereas saturated fatty acids are poor PPAR binders. However, ligand binding does not necessarily mean transcriptional activation. Therefore, it is important to investigate transactivation properties of dietary fatty acids as PPAR agonists and their role in metabolic reactions. Furthermore, human intervention studies comparing the effects of natural versus synthetic ligands side-by-side may reveal specific fatty acids that exert beneficial PPAR-mediated metabolic effects. The ability of PPARs to sense fatty acids and to mediate lipid metabolism, glucose metabolism and the inflammatory state makes them excellent targets for dietary modulation in order to prevent and treat the metabolic syndrome and associated diseases. This review discusses the role and function of PPARs and their ligands in light of the metabolic syndrome.


Subject(s)
Metabolic Syndrome/physiopathology , Peroxisome Proliferator-Activated Receptors/physiology , Animals , Humans , Ligands , Metabolic Syndrome/genetics , Metabolic Syndrome/metabolism , Peroxisome Proliferator-Activated Receptors/genetics , Peroxisome Proliferator-Activated Receptors/metabolism , Tissue Distribution
6.
J Nematol ; 34(1): 9-11, 2002 Mar.
Article in English | MEDLINE | ID: mdl-19265900

ABSTRACT

We report the cloning of a Heterodera glycines cDNA that has 72% identity at the amino acid level to a pectate lyase from Globodera rostochiensis. In situ hybridizations showed that the corresponding gene (Hg-pel-1) is expressed in the subventral esophageal gland cells of second-stage juveniles. The deduced amino acid sequence of the H. glycines cDNA shows homology to class III pectate lyases of bacterial and fungal origin.

7.
Nucleic Acids Res ; 29(7): 1616-22, 2001 Apr 01.
Article in English | MEDLINE | ID: mdl-11266565

ABSTRACT

The release of vast quantities of DNA sequence data by large-scale genome and expressed sequence tag (EST) projects underlines the necessity for the development of efficient and inexpensive ways to link sequence databases with temporal and spatial expression profiles. Here we demonstrate the power of linking cDNA sequence data (including EST sequences) with transcript profiles revealed by cDNA-AFLP, a highly reproducible differential display method based on restriction enzyme digests and selective amplification under high stringency conditions. We have developed a computer program (GenEST) that predicts the sizes of virtual transcript-derived fragments (TDFs) of in silico-digested cDNA sequences retrieved from databases. The vast majority of the resulting virtual TDFs could be traced back among the thousands of TDFs displayed on cDNA-AFLP gels. Sequencing of the corresponding bands excised from cDNA-AFLP gels revealed no inconsistencies. As a consequence, cDNA sequence databases can be screened very efficiently to identify genes with relevant expression profiles. The other way round, it is possible to switch from cDNA-AFLP gels to sequences in the databases. Using the restriction enzyme recognition sites, the primer extensions and the estimated TDF size as identifiers, the DNA sequence(s) corresponding to a TDF with an interesting expression pattern can be identified. In this paper we show examples in both directions by analyzing the plant parasitic nematode Globodera rostochiensis. Various novel pathogenicity factors were identified by combining ESTs from the infective stage juveniles with expression profiles of approximately 4000 genes in five developmental stages produced by cDNA-AFLP.


Subject(s)
DNA, Complementary/genetics , Gene Expression Profiling , Software , Animals , Expressed Sequence Tags , Gene Library , Nematoda/genetics , Polymorphism, Restriction Fragment Length , Transcription, Genetic
8.
Mol Plant Microbe Interact ; 13(8): 830-6, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10939254

ABSTRACT

A new strategy has been designed to identify putative pathogenicity factors from the dorsal or subventral esophageal glands of the potato cyst nematode Globodera rostochiensis. Three independent criteria were used for selection. First, genes of interest should predominantly be expressed in infective second-stage juveniles, and not, or to a far lesser extent, in younger developmental stages. For this, gene expression profiles from five different developmental stages were generated with cDNA-AFLP (amplified fragment length polymorphism). Secondly, the mRNA corresponding to such a putative pathogenicity factor should predominantly be present in the esophageal glands of pre-parasitic juveniles. This was checked by in situ hybridization. As a third criterion, these proteinaceous factors should be preceded by a signal peptide for secretion. Expression profiles of more than 4,000 genes were generated and three up-regulated, dorsal gland-specific proteins preceded by signal peptide for secretion were identified. No dorsal gland genes have been cloned before from plant-parasitic nematodes. The partial sequence of these three factors, A4, A18, and A41, showed no significant homology to any known gene. Their presence in the dorsal glands of infective juveniles suggests that these proteins could be involved in feeding cell initiation, and not in migration in the plant root or in protection against plant defense responses. Finally, the applicability of this new strategy in other plant-microbe interactions is discussed.


Subject(s)
Nematoda/pathogenicity , Nucleic Acid Amplification Techniques , Solanum tuberosum/parasitology , Animals , Base Sequence , DNA Primers , DNA, Complementary , In Situ Hybridization , Molecular Sequence Data , Nematoda/genetics , RNA, Messenger/genetics , Reproducibility of Results
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