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Query: UNIPROT:P06889 (Mol)
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The cardiac system has been a major target for intensive studies in the multi-scale modeling field for many years. Reproduction of the action potential and the ionic currents of single cardiomyocytes, as well as the construction of a whole organ model is well established. Still, there are major hurdles to overcome in creating a realistic and predictive functional cardiac model due to the lack of a profound understanding of the complex molecular interactions and their outcomes controlling both normal and pathological cardiophysiology. The recent advent of systems biology offers the conceptual and practical frameworks to tackle such biological complexities. This review provides an overview of major themes in the developing field of cardiac systems biology, summarizing some of the high-throughput experiments and strategies used to integrate the datasets, and various types of computational approaches used for developing useful quantitative models capable of predicting complex biological behavior.
J Mol Cell Cardiol 2008 Mar
PMID:An overview of cardiac systems biology. 1826 42

In routine practice, gastrointestinal stromal tumor (GIST) can usually be identified with relative ease on the basis of a rather simple immunohistochemical panel besides its characteristic morphology. Still, serious differential diagnostic problems may arise because of the heterogeneity of these tumors in both morphologic appearance and clinical behavior. In our case, we present a metastatic, ulcerative, hemorrhagic GIST with epithelioid appearance, which displayed diffuse pan cytokeratin (AE1/AE3) positivity beside CD117 expression. As carcinomas may also be CD117-positive, definitive diagnosis was confirmed by the detection of a hexanucleotide deletion in the exon 11 of c-kit. This case demonstrates that although gastric carcinoma more commonly ulcerates or causes hemorrhage than GIST, keratin-positive GIST should also be considered from a differential diagnostic point of view. In these cases, c-kit mutation analysis may be necessary.
Diagn Mol Pathol 2008 Dec
PMID:Keratin-positive gastrointestinal stromal tumor of the stomach mimicking gastric carcinoma: diagnosis confirmed by c-kit mutation analysis. 1838 54

Cyclodextrins resist hydrolysis by burying all bridge oxygens at their interior. Still, the rings can be opened by a small group of specialized enzymes, the cyclomaltodextrinases. Among them, the enzyme from Flavobacterium sp. no. 92 was mutated, crystallized and soaked with cyclodextrins, giving rise to four complex structures. One of them showed an alpha-cyclodextrin at the outer rim of the active center pocket. In the other complexes, alpha-, beta-and gamma-cyclodextrins were bound in a competent mode in the active center. The structures suggest that Arg464 functions as a chaperone guiding the substrates from the solvent into the active center. Over the last part of this pathway, the cyclodextrins bump on Phe274, which rotates the glucosyl group at subsite (+1) by about 120 degrees and fixes it in the new conformation. This induced fit was observed with all three major cyclodextrins. It makes the bridging oxygen between subsites (+1) and (-1) available for protonation by Glu340, which starts the hydrolysis. The mechanism resembles a spring-lock. The structural data were supplemented by activity measurements, quantifying the initial ring opening reaction for the major cyclodextrins and the transglucosylation activity for maltotetraose. Further activity data were collected for mutants splitting the tetrameric enzyme into dimers and for active center mutants.
J Mol Biol 2009 Jan 16
PMID:Structural base for enzymatic cyclodextrin hydrolysis. 1901 48

The trefoil factor family (TFF) comprises a group of small peptides which are highly expressed in tissues containing mucus-producing cells - especially in the mucosa lining the gastrointestinal tract. The peptides seem crucial for epithelial restitution and may work via other pathways than the conventional factors involved in restitution. In vitro studies have shown that the TFFs promote restitution using multiple mechanisms. The peptides also have other functionalities including interactions with the immune system. Moreover, therapeutic effects of the TFFs have been shown in several animal models of gastrointestinal damage. Still it is not clear which of their in vitro properties are involved in the in vivo mode of action. This review describes the TFF family with emphasis on their biological properties and involvement in mucosal protection and repair.
Cell Mol Life Sci 2009 Apr
PMID:The trefoil factor family - small peptides with multiple functionalities. 1909 84

Genetics, genomics, and biochemistry have all been of immense help in characterizing macromolecular cell entities and their interactions. Still, obtaining an overall picture of the functioning of even a simple unicellular species has remained a challenging task. One possible way to obtain a comprehensive picture has been described: by capitalizing on the observation that the overexpression on a multicopy plasmid of apparently any wild-type gene in yeast can lead to some negative effect on cell fitness (referring to the concept of "gene toxicity"), the FIG (fitness-based interferential genetics) approach was devised for selecting normal genes that are in antagonistic (and potentially also agonistic) relationship with a particular gene used as a reference. Herein, we take a complementary approach to FIG, by first selecting a "hypertoxic" allele of the reference gene--which easily provides the general possibility of obtaining gene products with the remarkable property of being inactive without altering their macromolecular interactivity--and then looking for the genes that interact functionally with this reference. Thus, FIG and the present approach (Trap-FIG), both taking advantage of the negative effects on cell fitness induced by various quantitative modulations in cellular networks, could potentially pave the way for the emergence of efficient in situ biochemistry.
Mol Genet Genomics 2009 Apr
PMID:A fitness-based interferential genetics approach using hypertoxic/inactive gene alleles as references. 1915 5

In vivo and in vitro labeled leukocytes have been shown to be very effective in detecting different infectious and inflammatory conditions. The model of labeled leukocyte imaging is based on the powerful mechanisms of chemotaxis exerted on activated leukocytes by chemo-attractants. The avidity of inflammatory cells for fluorodeoxyglucose (FDG) has led to the concept of labeling leukocytes with [(18F)]FDG ex vivo. This concept combines cell-bound radionuclide trafficking from the blood pool compartment to the lesion with the high resolution of positron emission tomography (PET) imaging. The further benefits of having a correlated anatomical map by implementing the acquisition on a hybrid PET/computed tomography (CT) device are obvious. The feasibility and the potential value of leukocyte PET(/CT) imaging in infection have been demonstrated. The available data suggest a high accuracy of the method. Still, leukocyte PET/CT should not be considered as the endpoint of infection imaging, since it only meets a part of the criteria of the ideal infection imaging agent. However, the common clinical need for specific detection of infection with anatomical precision, the availability of the components necessary for performing leukocyte PET/CT, their lack of toxicity or adverse effects and the absence of more superior tracers on the commercial market make it worthwhile to further investigate leukocyte PET/CT imaging in larger prospective series. The advantages of leukocyte PET/CT over the more conventional nuclear medicine and radiological methods makes this imaging tool likely to be useful in certain subsets of infected patients.
Q J Nucl Med Mol Imaging 2009 Feb
PMID:Imaging with FDG labeled leukocytes: is it clinically useful? 1918 32

Reproduction in vertebrates is controlled by the Hypothalamus-Pituitary-Gonad axis and the main hormone actions have been extensively described. Still, despite the scattered information in fish, accumulating evidence strongly indicates that corticosteroids play essential roles in reproductive mechanisms. An integrative approach is important for understanding these implications. Animal husbandry and physiological studies at molecular to organismal levels have revealed that these corticosteroids are regulators of fish reproductive processes. But their involvements appear strongly contrasted. Indeed, for both sexes, corticosteroids present either deleterious or positive effects on fish reproduction. In this review, the authors will attempt to gather and clarify the available information about these physiological involvements. The authors will also suggest future ways to prospect corticosteroid roles in fish reproduction.
Comp Biochem Physiol A Mol Integr Physiol 2009 Jul
PMID:Corticosteroids: Friends or foes of teleost fish reproduction? 1925 78

The existence of mtDNA recombination in animals has been confirmed by several case studies. Still, for Mytilus mussels possessing two divergent mitochondrial genomes (M and F), which can recombine, no recombination between coding sequences of highly diverged M and F genomes has been shown. Based on the full sequences of both genomes, it has been suggested that particularly low divergence observed within the mitochondrial nad3 gene of the Mytilus galloprovincialis mussel may be caused by its exceptionally low evolutionary rate. Here, we contribute a new pair of mitochondrial genomes typical for M. galloprovincialis and show that this low divergence is not a sign of evolutionary conservation but is rather caused by the acquisition of an F-related sequence by the published M genome of M. galloprovincialis. The most likely scenario for this apparent mtDNA-coding region recombination case is an assembly artifact.
Mol Biol Evol 2009 Jul
PMID:Is interlineage recombination responsible for low divergence of mitochondrial nad3 genes in Mytilus galloprovincialis? 1938 11

The red squirrel (Sciurus vulgaris) is a well-known forest animal distributed all over Europe. Still, we are far from having a firm knowledge of the species' phylogeography. This study investigates the genetic differentiation of S. vulgaris across the species' Eurasian range, using sequence data from the mitochondrial DNA gene (D-loop, 252 base pairs, cytochrome b, 359 base pairs), and eight variable autosomal microsatellite loci genotyped for 236 individuals. The results reveal the presence of two main mitochondrial phylogroups. The first clade comprises the individuals from the region of Calabria in southern Italy, belonging to the subspecies S. v. meridionalis, while the second clade contains the remainder of the studied individuals. Bayesian analysis of microsatellite genotypes resulted in three main clusterings corresponding to the three S. vulgaris subspecies: infuscatus, meridionalis and fuscoater. Geographical distribution of mtDNA haplotypes and mismatch analysis suggest a common refugium for the red squirrel across most of its present range from which expansion happened rather rapidly. The genotype mixing of italicus with northern populations could be a residual of postglacial expansion. The lack of mixing between the Calabrian lineage and the rest of European red squirrel haplotypes can be seen as evidence for distinct histories throughout the Pleistocene. Calabrian mtDNA probably diverged in an ice age contraction and remained isolated from the neighbouring squirrel populations until very recent times.
Mol Ecol 2009 Jun
PMID:Molecular phylogeography of European Sciurus vulgaris: refuge within refugia? 1945 79

Lymph nodes at different anatomical locations share similar architecture and operate on the basis of identical principles. Still, the quality of immune responses is modified substantially by the local peculiarities at the site of its induction. Here, we discuss how lymph node stroma cells contribute to functional differences between various lymph nodes, thus helping to explain why and how an immune response induced in skin draining peripheral lymph nodes differs from that elicited in the gut draining mesenteric lymph nodes. Stroma cells constitute a major part of the lymph node scaffold and control the flow of immune cells as well as soluble substances within the organ. Moreover, stroma cells express cytokines, chemokines as well as adhesion factors and thereby actively influence immune status. Lymph node transplantations and adoptive transfers of dendritic cells demonstrated that regional lymph node stroma cells differ in their ability to support mucosal tolerance, the induction of tissue tropism, and humoral immunity. This suggests that stroma cells shape tissue-specific immune responses and equip lymph nodes with unique functional properties that might originate during lymph node organogenesis.
J Mol Med (Berl) 2009 Oct
PMID:Mesenteric lymph node stroma cells in the generation of intestinal immune responses. 1964 72


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