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141.
Schweiger S Schneider R 《BioEssays : news and reviews in molecular, cellular and developmental biology》2003,25(4):356-366
Opitz BBB/G syndrome is a monogenic disorder that is characterized by malformations of the ventral midline. Investigations into the underlying genetic defects and the pathobiochemistry of this syndrome have already shed light on the mechanisms of both the physiological and the pathological development of the ventral midline, a complicated multistep process. Moreover, these studies have revealed the ubiquitin-dependent regulation of microtubule-associated phosphatase 2A, a central mechanism in many cellular processes. In this review, we summarize recent findings and speculate upon their implications for both medical and general research. 相似文献
142.
Effective population size as a driver for divergence of an antimicrobial peptide (Hymenoptaecin) in two common European bumblebee species 下载免费PDF全文
H. Michael G. Lattorff Mario Popp Susann Parsche Sophie Helbing Silvio Erler 《Biological journal of the Linnean Society. Linnean Society of London》2016,119(2):299-310
Social insects are the target of numerous pathogens. This is because the high density of closely‐related individuals frequently interacting with each other enhances the transmission and establishment of pathogens. This high selective pressure results in the rapid evolution of immune genes, which might be counteracted by a reduced effective population size (Ne) lowering the effectiveness of selection. We tested the effect of Ne on the evolutionary rate of an important immune gene for the antimicrobial peptide Hymenoptaecin in two common central European bumblebee species: Bombus terrestris and Bombus lapidarius. Both species are similar in their biology and are expected to be under similar selective pressures because pathogen prevalence does not differ between species. However, previous studies indicated a higher Ne in B. terrestris compared to B. lapidarius. We found high intraspecific variability in the coding sequence but low variability for silent polymorphisms in B. lapidarius. Estimates of long‐ and short‐term Ne were three‐ to four‐fold higher Ne in B. terrestris, although the species did not differ in census population sizes. The difference in Ne might result in less efficient selection and suboptimal adaptation of immune genes (e.g. hymenoptaecin) in B. lapidarius, and thus this species might become less resistant and more tolerant, turning into a superspreader of diseases. 相似文献
143.
Susann Kummer Max Fl?ttmann Bj?rn Schwanh?usser Christian Sieben Michael Veit Matthias Selbach Edda Klipp Andreas Herrmann 《PloS one》2014,9(4)
We studied the dynamics of the proteome of influenza virus A/PR/8/34 (H1N1) infected Madin-Darby canine kidney cells up to 12 hours post infection by mass spectrometry based quantitative proteomics using the approach of stable isotope labeling by amino acids in cell culture (SILAC). We identified 1311 cell proteins and, apart from the proton channel M2, all major virus proteins. Based on their abundance two groups of virus proteins could be distinguished being in line with the function of the proteins in genesis and formation of new virions. Further, the data indicate a correlation between the amount of proteins synthesized and their previously determined copy number inside the viral particle. We employed bioinformatic approaches such as functional clustering, gene ontology, and pathway (KEGG) enrichment tests to uncover co-regulated cellular protein sets, assigned the individual subsets to their biological function, and determined their interrelation within the progression of viral infection. For the first time we are able to describe dynamic changes of the cellular and, of note, the viral proteome in a time dependent manner simultaneously. Through cluster analysis, time dependent patterns of protein abundances revealed highly dynamic up- and/or down-regulation processes. Taken together our study provides strong evidence that virus infection has a major impact on the cell status at the protein level. 相似文献
144.
Stepan H Scheithauer S Dornhöfer N Krämer T Faber R 《Obesity (Silver Spring, Md.)》2006,14(5):770-773
Objectives: Obesity before and during pregnancy is associated with several obstetrics risk factors for both mother and fetus. The aim of this retrospective study was to analyze the influence of BMI before pregnancy on distinct perinatal parameters. Research Methods and Procedures: The study includes 5067 singleton pregnancies from 2001 to 2004 at the Department of Obstetrics and Gynecology, University of Leipzig. The study group was divided into BMI groups: <18.5, ≥18.5 to <25, ≥25 to <30, ≥30 to <35, ≥35 to <40, and ≥40 kg/m2. Analysis of perinatal data included rate of intrauterine death, rate of cesarean section and shoulder dystocia, time of hospital stay for mother and newborn, and gestational age of delivery. Neonatal outcome variables included percentage of newborns weighing >4000 grams, rate of umbilical cord pH <7.10, and rate of 1‐, 5‐, and 10‐minute Apgar scores of <8. Results: There was no difference in the gestational age at delivery among the groups. In the group with BMI ≥30 kg/m2, the cesarean section rate was significantly elevated to 25.1%, with a more dramatic increase up to 30.2% in the group with BMI ≥35 kg/m2 and 43.1% in the group with BMI ≥40 kg/m2, mainly because of a higher number of secondary cesarean sections. Although newborns of obese women showed worse initial neonatal adaptation, the 10‐minute Apgar values did not differ among the groups. The higher rate of operative deliveries and the trend to an increased rate of shoulder dystocia did not influence duration of the hospital stay for mothers and newborns or morbidity of both. Discussion: A high pre‐pregnancy BMI is clearly associated with a higher rate of cesarean section deliveries. However, under the compensating conditions of a tertiary perinatal center, overall morbidity of mothers and newborns seems not to be increased. 相似文献
145.
Polly J Phillips-Mason Sonya EL Craig Susann M Brady-Kalnay 《Cell Adhesion & Migration》2011,5(4):298-305
Dissolution of cell-cell adhesive contacts and increased cell-extracellular matrix adhesion are hallmarks of the migratory and invasive phenotype of cancer cells. These changes are facilitated by growth factor binding to receptor protein tyrosine kinases (RTKs). In normal cells, cell-cell adhesion molecules (CAMs), including some receptor protein tyrosine phosphatases (RPTPs), antagonize RTK signaling by promoting adhesion over migration. In cancer, RTK signaling is constitutive due to mutated or amplified RTKs, which leads to growth factor independence or autonomy. An alternative route for a tumor cell to achieve autonomy is to inactivate cell-cell CAMs such as RPTPs. RPTPs directly mediate cell adhesion and regulate both cadherin-dependent adhesion and signaling. In addition, RPTPs antagonize RTK signaling by dephosphorylating molecules activated following ligand binding. Both RPTPs and cadherins are downregulated in tumor cells by cleavage at the cell surface. This results in shedding of the extracellular, adhesive segment and displacement of the intracellular segment, altering its subcellular localization and access to substrates or binding partners. In this commentary we discuss the signals that are altered following RPTP and cadherin cleavage to promote cell migration. Tumor cells both step on the gas (RTKs) and disconnect the brakes (RPTPs and cadherins) during their invasive and metastatic journey.Key words: receptor protein tyrosine kinase, receptor-like protein tyrosine phosphatase, cadherins, cell adhesion, signal transduction, phospholipase C gamma, protein kinase C, catenins, IQGAP1 protein, regulated intramembrane proteolysis 相似文献
146.
147.
Mitogen-activated protein kinase (MAPK) signalling occurs in response to almost any change in the extracellular or intracellular milieu that affects the metabolism of the cell, organ or the entire organism. MAPK-dependent signal transduction is required for physiological metabolic adaptation, but inappropriate MAPK signalling contributes to the development of several interdependent pathological traits, collectively known as metabolic syndrome. Metabolic syndrome leads to life-threatening clinical consequences, such as type 2 diabetes. This Review provides an overview of the MAPK-signalling mechanisms that underly basic cellular metabolism, discussing their link to disease. 相似文献
148.
Runge S Schimmer S Oschmann J Schiødt CB Knudsen SM Jeppesen CB Madsen K Lau J Thøgersen H Rudolph R 《Biochemistry》2007,46(19):5830-5840
Glucagon-like peptide-1 (GLP-1) and exendin-4 (Ex4) are homologous peptides with established potential for treatment of type 2 diabetes. They bind and activate the pancreatic GLP-1 receptor (GLP-1R) with similar affinity and potency and thereby promote insulin secretion in a glucose-dependent manner. GLP-1R belongs to family B of the seven transmembrane G-protein coupled receptors. The N-terminal extracellular domain (nGLP-1R) is a ligand binding domain with differential affinity for Ex4 and GLP-1: low affinity for GLP-1 and high affinity for exendin-4. The superior affinity of nGLP-1R for Ex4 was previously explained by an additional interaction between nGLP-1R and the C-terminal Trp-cage of Ex4. In this study we have combined biophysical and pharmacological approaches thus relating structural properties of the ligands in solution to their relative binding affinity for nGLP-1R. We used both a tracer competition assay and ligand-induced thermal stabilization of nGLP-1R to measure the relative affinity of full length, truncated, and chimeric ligands for soluble refolded nGLP-1R. The ligands in solution and the conformational consequences of ligand binding to nGLP-1R were characterized by circular dichroism and fluorescence spectroscopy. We found a correlation between the helical content of the free ligands and their relative binding affinity for nGLP-1R, supporting the hypothesis that the ligands are helical at least in the segment that binds to nGLP-1R. The Trp-cage of Ex4 was not necessary to maintain a superior helicity of Ex4 compared to GLP-1. The results suggest that the differential affinity of nGLP-1R is explained almost entirely by divergent residues in the central part of the ligands: Leu10-Gly30 of Ex4 and Val16-Arg36 of GLP-1. In view of our results it appears that the Trp-cage plays only a minor role for the interaction between Ex4 and nGLP-1R and for the differential affinity of nGLP-1R for GLP-1 and Ex4. 相似文献
149.
Johanna Wetzel Susann Herrmann Lakshmipuram Seshadri Swapna Dhaneswar Prusty Arun T. John Peter Maya Kono Sidharth Saini Srinivas Nellimarla Tatianna Wai Ying Wong Louisa Wilcke Olivia Ramsay Ana Cabrera Laura Biller Dorothee Heincke Karen Mossman Tobias Spielmann Christian Ungermann John Parkinson Tim W. Gilberger 《The Journal of biological chemistry》2015,290(3):1712-1728
To survive and persist within its human host, the malaria parasite Plasmodium falciparum utilizes a battery of lineage-specific innovations to invade and multiply in human erythrocytes. With central roles in invasion and cytokinesis, the inner membrane complex, a Golgi-derived double membrane structure underlying the plasma membrane of the parasite, represents a unique and unifying structure characteristic to all organisms belonging to a large phylogenetic group called Alveolata. More than 30 structurally and phylogenetically distinct proteins are embedded in the IMC, where a portion of these proteins displays N-terminal acylation motifs. Although N-terminal myristoylation is catalyzed co-translationally within the cytoplasm of the parasite, palmitoylation takes place at membranes and is mediated by palmitoyl acyltransferases (PATs). Here, we identify a PAT (PfDHHC1) that is exclusively localized to the IMC. Systematic phylogenetic analysis of the alveolate PAT family reveals PfDHHC1 to be a member of a highly conserved, apicomplexan-specific clade of PATs. We show that during schizogony this enzyme has an identical distribution like two dual-acylated, IMC-localized proteins (PfISP1 and PfISP3). We used these proteins to probe into specific sequence requirements for IMC-specific membrane recruitment and their interaction with differentially localized PATs of the parasite. 相似文献
150.
Janna Schneppenheim Susann Hüttl Torben Mentrup Renate Lüllmann-Rauch Michelle Rothaug Michael Engelke Kai Dittmann Ralf Dressel Masatake Araki Kimi Araki Jürgen Wienands Regina Fluhrer Paul Saftig Bernd Schr?der 《Molecular and cellular biology》2014,34(8):1398-1411
We reported recently that the presenilin homologue signal peptide peptidase-like 2a (SPPL2a) is essential for B cell development by cleaving the N-terminal fragment (NTF) of the invariant chain (li, CD74). Based on this, we suggested that pharmacological modulation of SPPL2a may represent a novel approach to deplete B cells in autoimmune disorders. With regard to reported overlapping substrate spectra of SPPL2a and its close homologue, SPPL2b, we investigated the role of SPPL2b in CD74 NTF proteolysis and its impact on B and dendritic cell homeostasis. In heterologous expression experiments, SPPL2b was found to cleave CD74 NTF with an efficiency simliar to that of SPPL2a. For in vivo analysis, SPPL2b single-deficient and SPPL2a/SPPL2b double-deficient mice were generated and examined for CD74 NTF turnover/accumulation, B cell maturation and functionality, and dendritic cell homeostasis. We demonstrate that in vivo SPPL2b does not exhibit a physiologically relevant contribution to CD74 proteolysis in B and dendritic cells. Furthermore, we reveal that both proteases exhibit divergent subcellular localizations in B cells and different expression profiles in murine tissues. These findings suggest distinct functions of SPPL2a and SPPL2b and, based on a high abundance of SPPL2b in brain, a physiological role of this protease in the central nervous system. 相似文献