TY - JOUR AB - BACKGROUND: This study investigates the influence of maternal stress during pregnancy on maternal insulin sensitivity and Interleukin-6 (IL-6) levels in pregnant women (N = 277) in dependence of pre-pregnancy Body-Mass-Index (BMI). METHODS: Gestational diabetes was diagnosed in 80 women. We used the Patient Health Questionnaire (PHQ-D) to investigate maternal stress during pregnancy with a higher scoring indicating higher maternal stress level. IL-6 and cortisol were measured and maternal insulin sensitivity was assessed with the non-esterified fatty acid insulin sensitivity index (NEFA-ISI). Generalized Linear Model analysis was used to analyze effects within different stress groups. RESULTS: Maternal low stress symptoms during pregnancy showed no significant association with maternal insulin sensitivity or IL-6. Higher cortisol levels during pregnancy were associated with elevated IL-6 concentrations. Pre-pregnancy BMI had the strongest positive effect on IL-6 levels and was negatively associated with insulin sensitivity during pregnancy. CONCLUSIONS: Therefore, preconceptional interventions to reduce BMI are needed to improve maternal metabolism during pregnancy. AU - Bauer, I. AU - Schleger, F. AU - Hartkopf, J. AU - Veit, R. AU - Breuer, M. AU - Schneider, N. AU - Pauluschke-Fröhlich, J.* AU - Peter, A. AU - Preissl, H. AU - Fritsche, A. AU - Fritsche, L. C1 - 64534 C2 - 52261 CY - 112 Robinson Rd, Robinson, Singapore TI - Pre-pregnancy BMI but not mild stress directly influences Interleukin-6 levels and insulin sensitivity during late pregnancy. JO - Front. Biosci. VL - 27 IS - 2 PB - Imr Press PY - 2022 SN - 1093-9946 ER - TY - JOUR AB - In order to deal with endogenous and exogenous factors, including radiation or pathogens, cells evolved different strategies. This includes highly complex processes such as DNA damage response, senescence, cell death, and inflammatory reactions. Recent research indicates an interconnection between the mentioned cellular pathways whilst all of them seem to play a role in induction and progression, but also the prevention of cancerous diseases and therefore qualify for potential prevention and treatment strategies. On the basis of their pivotal functions in cancer biology in general, each of the cellular processes represents promising single therapeutic targets. Further, due to their strong interconnection, targeting all of them in a multimodal approach could be another promising strategy to treat cancer. We, therefore, review the mechanisms of DNA damage induction, detection and repair as well as the induction of cell death. Further, features of senescence and mechanism of inflammation induction and abrogation are outlined. A special focus is set on how senescence and inflammation are related to diseases and how targeting them could contribute to improvement of cancer therapies. AU - Wunderlich, R. AU - Rühle, P.F.* AU - Deloch, L.* AU - Unger, K. AU - Hess J. AU - Zitzelsberger, H. AU - Lauber, K.* AU - Frey, B.* AU - Gaipl, U.S.* C1 - 51156 C2 - 42662 SP - 348-369 TI - Interconnection between DNA damage, senescence, inflammation, and cancer. JO - Front. Biosci. VL - 22 PY - 2017 SN - 1093-9946 ER - TY - JOUR AB - Epithelial- mesenchymal- transition (EMT) is a crucial process during morphogenesis of multi-cellular organisms. EMT not only is a normal developmental process but also plays a role in tumor invasion and metastasis. Indeed, molecules involved in EMT, such as the transcription factor and E-cadherin repressor Slug (SNAI2), have recently been demonstrated to be important for cancer cells to down-regulate epithelial markers and up-regulate mesenchymal markers in order to become motile and invasive. Here we summarize major studies focusing on Slug expression in human tumor samples. We review a total of 13 studies involving 1150 cases from 9 different types of tumors. It is becoming clear that this transcription factor plays a role in the progression of some tumor types, including breast and gastric cancer. Interestingly, Slug expression is not always associated with down-regulation of E-cadherin. The mode of action, the signaling pathways involved in its regulation, and the interplay with other EMT regulators need to be addressed in future studies in order to fully understand Slug's role in tumor progression. AU - Alves, C.C.* AU - Carneiro, F.* AU - Hoefler, H. AU - Becker, K.-F.* C1 - 952 C2 - 26115 SP - 3041-3050 TI - Role of the epithelial-mesenchymal transition regulator Slug in primary human cancers. JO - Front. Biosci. VL - 14 PB - Frontiers In Bioscience Inc PY - 2009 SN - 1093-9946 ER - TY - JOUR AB - In humans up to 80% of the information received from the outside world is processed by the visual pathway. Therefore, understanding the molecular and cellular bases of the formation of the retinofugal projection has been in the focus of research during the last decades. Besides our interest in the development of the visual pathway per se this circuit is also an excellent model system to study axon guidance, midline crossing, and formation of topographic neuronal maps in general. The generation of genetic animal models as well as the design of in vitro loss- and gain-of-function paradigms have provided insight into transcriptional networks, identified signalling molecules, extracellular matrix components, morphogens, and activity patterns which are involved in the establishment of the visual pathway. To provide a picture as complete as possible, we will summarize molecular mechanisms involved in axon guidance and retinotopic mapping as well as neuronal activity shaping retinal and thalamocortical projections focusing on the mouse as a model system and highlight discoveries made in other organisms that contribute to our understanding. AU - Haupt, C. AU - Huber, A.B. C1 - 332 C2 - 25635 SP - 3136-3149 TI - How axons see their way - axonal guidance in the visual system. JO - Front. Biosci. VL - 13 IS - 8 PB - Frontiers in bioscience Inc. PY - 2008 SN - 1093-9946 ER - TY - JOUR AB - It is unclear what role vision plays in guiding mouse behaviour, since the mouse eye is of comparably low optical quality, and mice are considered to rely primarily on other senses. All C3H substrains are homozygous for the Pde6b(rd1) mutation and get blind by weaning age. To study the impact of the Pde6b(rd1) mutation on mouse behaviour and physiology, sighted C3H (C3H.Pde6b+) and normal C3H/HeH mice were phenotyped for different aspects. We confirmed retinal degeneration 1 in C3H/HeH mice, and the presence of a morphologically normal retina as well as visual ability in C3H.Pde6b+ mice. However, C3H.Pde6b+ mice showed an abnormal retinal function in the electroretinogram response, indicating that their vision was not normal as expected. C3H.Pde6b+ mice showed reduced latencies for several behaviours without any further alterations in these behaviours in comparison to C3H/HeH mice, suggesting that visual ability, although impaired, enables earlier usage of the behavioural repertoire in a novel environment, but does not lead to increased activity levels. These results emphasize the importance of comprehensive behavioural and physiological phenotyping. AU - Hölter, S.M. AU - Dalke, C. AU - Kallnik, M. AU - Becker, L. AU - Horsch, M. AU - Schrewe, A. AU - Favor, J. AU - Klopstock, T.* AU - Beckers, J. AU - Ivandic, B.* AU - Gailus-Durner, V. AU - Fuchs, H. AU - Hrabě de Angelis, M. AU - Graw, J. AU - Wurst, W. C1 - 2337 C2 - 25320 SP - 5810-5823 TI - 'Sighted C3H' mice - a tool for analysing the influence of vision on mouse behaviour? JO - Front. Biosci. VL - 13 IS - 15 PB - Frontiers in Bioscience Inc. PY - 2008 SN - 1093-9946 ER - TY - JOUR AB - Epithelial cell adhesion molecule EpCAM is strongly over-expressed in a variety of carcinomas where it is involved in signalling events resulting in increased expression of target genes such as c-Myc, cyclins and others, eventually conferring cells an oncogenic phenotype. However, EpCAM is also expressed in a series of healthy epithelia, albeit generally to a far lesser extend. We have uncovered differential glycosylation of EpCAM as a means to discriminate normal from malignant tissues. EpCAM was hyperglycosylated in carcinoma tissue as compared with autologous normal epithelia. All three N-glycosylation consensus sequences within EpCAM's extracellular domain were used in human and murine cells. We show that glycosylation at asparagine198 is crucial for protein stability. Mutants of EpCAM that substitute asparagine198 for alanine showed a decreased overall expression and half-life of the molecule at the plasma membrane. This is of considerable importance with respect to EpCAM variants expressed in normal tissue, where it might reveal to be less stable and thus may have repercussions on functionality. AU - Münz, M. AU - Fellinger, K.* AU - Hofmann, T.* AU - Schmitt, B. AU - Gires, O. C1 - 5596 C2 - 25886 SP - 5195-5201 TI - Glycosylation is crucial for stability of tumour and cancer stem cell antigen EpCAM. JO - Front. Biosci. VL - 13 PB - Landmark Edition PY - 2008 SN - 1093-9946 ER - TY - JOUR AB - The optokinetic drum has become an appropriate tool to examine visual properties of mice. We performed baseline measurements using mice of the inbred strains C3H, C57BL/6, BALB/c, JF1, 129 and DBA/2 at the age of 8-15 weeks. Each individual C57BL/6, 129 and JF1 mouse was reliably identified as non-affected in vision by determining head-tracking responses. C3H mice were used as negative control because of their inherited retinal degeneration; as expected, they did not respond to the moving stripe pattern. Surprisingly, BALB/c and DBA/2 mice showed the same result. Electroretinography, funduscopy and histology of BALB/c mice did not reveal any abnormality concerning the structure or function of the retina and the remaining eye. Therefore, it might be assumed that BALB/c mice suffer from disturbances of the central visual system. Preliminary results from linkage analysis of the non-responding phenotype in the BALB/c mice indicate a recessive, monogenic mode of inheritance; the causative gene is located on chromosome 7, but significantly different from the albino locus. In conclusion, C57BL/6, 129 and JF1 represent appropriate inbred strains for high throughput screenings with the optokinetic drum. AU - Puk, O. AU - Dalke, C. AU - Hrabě de Angelis, M. AU - Graw, J. C1 - 1516 C2 - 25220 SP - 6269-6275 TI - Variation of the response to the optokinetic drum among various strains of mice. JO - Front. Biosci. VL - 13 PY - 2008 SN - 1093-9946 ER -