Reduced strength after passive stretch of the human plantarflexors.

The purpose of this study was to assess strength performance after an acute bout of maximally tolerable passive stretch (PS(max)) in human subjects. Ten young adults (6 men and 4 women) underwent 30 min of cyclical PS(max) (13 stretches of 135 s each over 33 min) and a similar control period (Con) of no stretch of the ankle plantarflexors. Measures of isometric strength (maximal voluntary contraction), with twitch interpolation and electromyography, and twitch characteristics were assessed before (Pre), immediately after (Post), and at 5, 15, 30, 45, and 60 min after PS(max) or Con. Compared with Pre, maximal voluntary contraction was decreased at Post (28%) and at 5 (21%), 15 (13%), 30 (12%), 45 (10%), and 60 (9%) min after PS(max) (P < 0.05). Motor unit activation and electromyogram were significantly depressed after PS(max) but had recovered by 15 min. An additional testing trial confirmed that the torque-joint angle relation may have been temporarily altered, but at Post only. These data indicate that prolonged stretching of a single muscle decreases voluntary strength for up to 1 h after the stretch as a result of impaired activation and contractile force in the early phase of deficit and by impaired contractile force throughout the entire period of deficit.     

Synergism among lysophosphatidic acid, beta1A integrins, and epidermal growth factor or platelet-derived growth factor in mediation of cell migration.

GD25 cells lacking the beta1 integrin subunit or expressing beta1A with certain cytoplasmic mutations have poor directed cell migration to platelet-derived growth factor (PDGF) or epidermal growth factor (EGF), ligands of receptor tyrosine kinases, or to lysophosphatidic acid (LPA), a ligand of G-protein-coupled receptors (Sakai, T., Zhang, Q., F?ssler, R., and Mosher, D. F. (1998) J. Cell Biol. 141, 527-538 and Sakai, T., Peyruchaud, O., F?ssler, R., and Mosher, D. F. (1998) J. Biol. Chem. 273, 19378-19382). We demonstrate here that LPA synergizes with signals induced by beta1A integrins and ligated EGF or PDGF receptors to modulate migration. When LPA was mixed with EGF or PDGF, migration was greater than with EGF or PDGF alone. The enhancement was greater for beta1A-expressing cells than for beta1-null cells. Cells expressing beta1A with mutations of prolines or tyrosines in conserved cytoplasmic NPXY motifs had blunted migratory responses to mixtures of LPA and EGF or PDGF. The major effects on beta1A-expressing cells of LPA when combined with EGF or PDGF were to sensitize cells so that maximal responses were obtained with >10-fold lower concentrations of growth factor and increase the chemokinetic component of migration. Sensitization by LPA was lost when cells were preincubated with pertussis toxin or C3 exotransferase. There was no evidence for transactivation or sensitization of receptors for EGF or PDGF by LPA. EGF or PDGF and LPA caused activation of mitogen-activated protein kinase by pertussis toxin-insensitive and -sensitive pathways respectively, but activation was not additive. These findings indicate that signaling pathways initiated by the cytoplasmic domains of ligated beta1A integrins and tyrosine kinase receptors interact with signaling pathways initiated by LPA to facilitate directed cell migration.     

Apport de la tomographie par émission de positons au 18F-fluorodéoxyglucose (TEP-FDG) dans la prise en charge du cancer du canal anal

ObjectiveTo evaluate the contribution of FDG-PET in the management of anal carcinoma, with special emphasis on its impact on therapeutic strategy.Materials and methodsFrom March 2005 to August 2008, 48 PET were performed on 43 patients with anal epidermoid carcinoma, in initial staging (IS: 20 exams), therapeutic response assessment (TRA: 11), and recurrence assessment (RA: 17). We compared initial therapeutic strategies defined on conventional assessment results, to final ones chosen after PET.ResultsPET revealed lesions that were undetected by conventional investigation in 23% of cases (IS: 25%; TRA: 18%; RA: 23%) and cleared suspicious lesions in 21% of cases (IS: 10%; TRA: 18%; RA: 35%). It influenced the therapeutic strategy, and sometimes even modified it radically, in 44% of cases (IS: 35%; TRA: 54%; RA: 47%). This therapeutic impact was stronger in settings with diagnostic ambiguity, in which PET allowed to specify the diagnosis and to orientate consequently the therapeutic choice.ConclusionPET is interesting in the management of anal carcinoma, especially in uncertain diagnostic settings, in which the metabolic information brought allows to influence the therapeutic choice in almost half of the cases.     

The genetics of cell migration in Drosophila melanogaster and Caenorhabditis elegans development.

Cell migrations are found throughout the animal kingdom and are among the most dramatic and complex of cellular behaviors. Historically, the mechanics of cell migration have been studied primarily in vitro, where cells can be readily viewed and manipulated. However, genetic approaches in relatively simple model organisms are yielding additional insights into the molecular mechanisms underlying cell movements and their regulation during development. This review will focus on these simple model systems where we understand some of the signaling and receptor molecules that stimulate and guide cell movements. The chemotactic guidance factor encoded by the Caenorhabditis elegans unc-6 locus, whose mammalian homolog is Netrin, is perhaps the best known of the cell migration guidance factors. In addition, receptor tyrosine kinases (RTKs), and FGF receptors in particular, have emerged as key mediators of cell migration in vivo, confirming the importance of molecules that were initially identified and studied in cell culture. Somewhat surprisingly, screens for mutations that affect primordial germ cell migration in Drosophila have revealed that enzymes involved in lipid metabolism play a role in guiding cell migration in vivo, possibly by producing and/or degrading lipid chemoattractants or chemorepellents. Cell adhesion molecules, such as integrins, have been extensively characterized with respect to their contribution to cell migration in vitro and genetic evidence now supports a role for these receptors in certain instances in vivo as well. The role for non-muscle myosin in cell motility was controversial, but has now been demonstrated genetically, at least in some cell types. Currently the best characterized link between membrane receptor signaling and regulation of the actin cytoskeleton is that provided by the Rho family of small GTPases. Members of this family are clearly essential for the migrations of some cells; however, key questions remain concerning how chemoattractant and chemorepellent signals are integrated within the cell and transduced to the cytoskeleton to produce directed cell migration. New types of genetic screens promise to fill in some of these gaps in the near future.     

It started with a dream: Paul's dream (Acts 16,9?10) and Aeneas as a biblical example of dreams as intercultural legitimation strategy.

Dreams are often used to promote religion, or to propagate an interpretation of religion, or to bring political ideas to the fore. A dream can be used as an indication of divine help and thus it is a perfect tool for promoting ideas. Dreams figure in religious propaganda in Christian, Jewish, and Muslim traditions (e.g., in Osama bin Laden's tapes). In classical literature, we find many kings, emperors, or generals who had visions or dreams, especially in association with their accession to power. It is the thesis of this article that in the encounter between Jewish (-Christian) cultures and the Hellenistic world dreams were shared as possible means of divine communication. An important example is the dream in Acts 16,9?10, the most Hellenistic dream of the New Testament. This dream is part of a larger unit, Paul's new move from Asia to Europe. I will try to show that the author of Acts combines here the story of Aeneas (e.g., as told by Virgil) and the story of Jesus, an interesting merging of two cultures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Monoclonal antibodies to alpha-chain regions of human fibrinogen that participate in polymer formation

Monoclonal antibodies have been generated against a cross-link-containing derivative of alpha polymer (alpha XLCNBr), isolated following CNBr digestion of fibrin [Sobel, J. H., Ehrlich, P. H., Birken, S., Saffran, A. J., & Canfield, R. E. (1983) Biochemistry (preceding paper in this issue)]. One cloned cell line (F-102) was chosen for characterization based on its apparent specificity for the A alpha-chain region A alpha 518-584 (CNBr X). A second line (F-103) was selected because of its anti-A alpha 241-476 (CNBr VIII) properties. These two regions of the A alpha chain have previously been implicated as major contributors to the cross-linking process that leads to alpha-polymer formation. Radioimmunoassays have been developed, employing the immunoglobulins produced by clones F-102 and F-103. These assays have been applied, in conjunction with high-performance liquid chromatography purified tryptic and chymotryptic derivatives of CNBr VIII and CNBr X, to localize the respective determinants involved in antibody binding. In each case, virtually full immunoreactivity was exhibited by both the CNBr fragment and a single tryptic or chymotryptic peptide originating from it. These findings indicate that sequence-specific, rather than conformational, determinants were operative in the generation of antibodies F-102 and F-103. The epitope recognized by F-102 was localized to the region of A alpha 540-554, while the F-103 binding site resided within A alpha 259-276. When these radioimmunoassays were applied to study the relative immunoreactivity exhibited by a variety of fibrinogen derivatives, the results obtained support earlier suggestions that the COOH-terminal portion of the A alpha chain contains regions of random conformation.     

Segmentally repeated pattern of expression of a cell surface glycoprotein in Drosophila embryos

We report here that a previously described cell surface antigen (Brower, Smith & Wilcox, 1980) is expressed in a segmentally repeating pattern of stripes in the epidermis and nervous system of segmented Drosophila embryos. We also report that the antigenic activity is found on two closely related cell surface glycoproteins. The pattern of expression of this antigen is reminiscent of the expression of some segmentation genes and is affected by mutation of at least two of these genes, fushi tarazu and paired. Thus these glycoproteins are candidates for cell surface molecules involved in carrying out the patterning processes controlled by segmentation genes.     

The distribution of Escherichia coli recA protein bound to duplex DNA with single-stranded ends

A short single-stranded tail on one end of an otherwise duplex DNA molecule enables recA protein, in the presence of ATP and MgCl2, to form a complex with the DNA which extends into the duplex portion of the molecule. Nuclease protection studies at a concentration of MgCl2 which permits homologous pairing showed that cleavage by restriction endonucleases at sites throughout the duplex region was inhibited, whereas digestion by DNase I was not affected. These results indicate that recA protein binds to the duplex portion of tailed DNA allowing access by DNase I to a random sample of the many sites at which it cleaves, but providing limited protection of the relatively rare restriction sites. Electron microscopy revealed that the recA nucleoprotein complex with duplex DNA is indeed a segmented or interrupted filament that, with time, extends further from the single-stranded tail into the duplex region. recA protein binding extended into the duplex region more rapidly for duplexes with 5' tails than for those with 3' tails. These observations show that recA protein translocates from a single-stranded region into duplex DNA in the form of a segmented filament by a mechanism that is not strongly polarized.     

L-proline uptake in human fibroblasts: evidence for a high-affinity system in addition to system A

Proline uptake was studied in human skin fibroblasts by simultaneous running of kinetic and inhibition experiments on the same cell lines. Two systems for proline uptake were shown: a high-affinity system not inhibited by alpha-(methylamino)isobutyric acid and a low affinity system inhibited by this amino acid (i.e. system A). These results appear to be of interest, firstly because up till now, system A was considered preferable for proline uptake in human fibroblasts, and secondly because they illustrate the need for combined inhibition and kinetic studies of amino acid uptake, especially when the substrate concentration range used and the respective Km of the systems do not allow their detection by kinetic analysis alone. Furthermore, this high-affinity system may have major physiological implications.