Publications by authors named "Jeffrey G Williams"

College soccer players suffer from hamstring injuries due to inflexibility and repetitive motions involving intense hamstring lengthening and contraction during sport. Although it is a popular intervention for muscular injury, there exists limited evidence of the effects of therapeutic cupping on hamstring flexibility. To determine the effect of cupping therapy on hamstring flexibility in college soccer players.

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DIF-1 (differentiation-inducing factor1) is a polyketide produced by Dictyostelium prespore cells which induces initially uncommitted cells to differentiate as prestalk cells. Exposure of cells to DIF-1 causes transitory hypo-phosphorylation of seven serine residues in YelA, a protein with a region of strong homology to the MIF4G domain of the eukaryotic initiation factor eIF4G. Based upon its domain architecture, which in one important aspect closely resembles that of Death-Associated Protein 5 (DAP5), we predict a role in stimulating internal ribosome entry-driven mRNA translation.

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Differentiation-inducing factor-1 (DIF-1) is a polyketide that induces Dictyostelium amoebae to differentiate as prestalk cells. We performed a global quantitative screen for phosphorylation changes that occur within the first minutes after addition of DIF-1, using a triple-label SILAC approach. This revealed a new world of DIF-1-controlled signaling, with changes in components of the MAPK and protein kinase B signaling pathways, components of the actinomyosin cytoskeletal signaling networks, and a broad range of small GTPases and their regulators.

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When Dictyostelium cells are hyperosmotically stressed, STATc is activated by tyrosine phosphorylation. Unusually, activation is regulated by serine phosphorylation and consequent inhibition of a tyrosine phosphatase: PTP3. The identity of the cognate tyrosine kinase is unknown, and we show that two tyrosine kinase-like (TKL) enzymes, Pyk2 and Pyk3, share this function; thus, for stress-induced STATc activation, single null mutants are only marginally impaired, but the double mutant is nonactivatable.

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Cellular adaptation to changes in environmental osmolarity is crucial for cell survival. In Dictyostelium, STATc is a key regulator of the transcriptional response to hyperosmotic stress. Its phosphorylation and consequent activation is controlled by two signaling branches, one cGMP- and the other Ca(2+)-dependent, of which many signaling components have yet to be identified.

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Introduction/background: Optimal baseball throwing mechanics require a significant contribution of thoracolumbar motion, particularly in the sagittal and transverse planes. This motion is key for proper transmission of forces from the lower to upper extremity, thereby minimizing a throwing athlete's risk of injury and maximizing athletic performance.

Purpose: To define the active-assisted thoracolumbar ROM of both baseball pitchers and position players and to compare these motions both within and between groups.

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Background: Cell behaviour is tightly determined by sensing and integration of extracellular changes through membrane detectors such as receptors and transporters and activation of downstream signalling cascades. Arrestin proteins act as scaffolds at the plasma membrane and along the endocytic pathway, where they regulate the activity and the fate of some of these detectors. Members of the arrestin clan are widely present from unicellular to metazoa, with roles in signal transduction and metabolism.

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MrfA, a transcription factor that regulates Dictyostelium prestalk cell differentiation, is an orthologue of the metazoan myelin gene regulatory factor (MRF) proteins. We show that the MRFs contain a predicted transmembrane domain, suggesting that they are synthesised as membrane-tethered proteins that are then proteolytically released. We confirm this for MrfA but report a radically different mode of processing from that of paradigmatic tethered transcriptional regulators, which are cleaved within the transmembrane domain by a dedicated protease.

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DIF-1, a chlorinated hexaphenone produced by developing Dictyostelium cells, induces prestalk differentiation. DimB is a bZIP transcription factor that accumulates in the nucleus upon exposure to DIF-1, where it directly activates transcription of DIF-responsive genes. The signaling steps upstream of DimB and downstream of DIF-1 are entirely unknown.

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Purpose/background: To compare the acute effects of two passive stretches on pectoralis minor length and scapular kinematics among a group of collegiate swimmers.

Methods: The study was a descriptive design with repeated measures. All procedures were conducted in a biomechanics laboratory and collegiate swimming facility.

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Objectives: To determine the strength of the relationship between latissimus dorsi stiffness and altered scapular kinematics among swimmers.

Design: Cross sectional.

Setting: Laboratory.

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The prestalk region of the Dictyostelium slug is comprised of an anterior population of pstA cells and a posterior population of pstO cells. They are distinguished by their ability to utilize different parts of the promoter of the ecmA gene. We identify, by mutational analysis and DNA transformation, CA-rich sequence elements within the ecmA promoter that are essential for pstA-specific expression and sufficient to direct pstA-specific expression when multimerised.

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SH2 domains are integral to many animal signaling pathways. By interacting with specific phosphotyrosine residues, they provide regulatable protein-protein interaction domains. Dictyostelium is the only nonmetazoan with functionally characterized SH2 domains, but the cognate tyrosine kinases are unknown.

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The Dictyostelium transcription factor STATc is tyrosine phosphorylated and accumulates in the nucleus when cells are exposed either to hyper-osmotic stress or to the prestalk-inducing polyketide DIF-1. In the case of stress STAT activation is mediated by regulated dephosphorylation; whereby two serine residues on PTP3, the tyrosine phosphatase that de-activates STATc, become phosphorylated after exposure to stress so inhibiting enzymatic activity. We now show that the more highly regulated of the two PTP3 serine residues, S747, is also phosphorylated in response to DIF-1, suggesting a common activation mechanism.

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In response to the signaling polyketide DIF-1 DimB directly activates transcription of the ecmB gene in pstB cells; a subset of the prestalk cells that are the precursors of the basal disc. We show that the promoter of pspA, a prespore-specific gene, also contains a DimB binding site. Mutation of this site causes ectopic expression in the prestalk region and ChIP analysis shows that DIF-1 induces binding of DimB to the pspA promoter.

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SmdA is a Dictyostelium orthologue of the SET/MYND chromatin re-modelling proteins. In developing structures derived from a null mutant for smdA (a smdA- strain), prestalk patterning is normal, but using a prespore lacZ reporter fusion, there is ectopic accumulation of beta-galactosidase in the prestalk region. As wild type slugs migrate, there is continual forward movement and re-differentiation of prespore cells into prestalk cells.

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Exposure of monolayer Dictyostelium cells to the signalling polyketide DIF-1 causes DimB, a bZIPtranscription factor, to accumulate in the nucleus where it induces prestalk gene expression. Here we analyse DimB signalling during normal development. In slugs DimB is specifically nuclear enriched in the pstB cells; a cluster of vital dye-staining cells located on the ventral surface of the posterior, prespore region.

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Dictyostelium is the only non-metazoan with functionally analyzed SH2 domains and studying them can give insights into their evolution and wider potential. LrrB has a novel domain configuration with leucine-rich repeat, 14-3-3 and SH2 protein-protein interaction modules. It is required for the correct expression of several specific genes in early development and here we characterize its role in later, multicellular development.

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cotC requires the transcription factor CudA for its expression in the posterior, prespore cells of the slug, while the expL7 gene requires CudA for its expression in the anterior, tip-organiser region. In order to identify additional transcription factors that might mediate tip-organiser specific expression, we performed affinity chromatography on slug nuclear extracts. The affinity matrix bore cap-site distal sequences from region A of the expL7 promoter; an essential region located upstream of the CudA binding domain.

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Any established or aspiring model organism must justify itself using two criteria: does the model organism offer experimental advantages not offered by competing systems? And will any discoveries made using the model be of wider relevance? This review addresses these issues for the social amoeba Dictyostelium and highlights some of the organisms more recent applications. These cover a remarkably wide gamut, ranging from sociobiological to medical research with much else in between.

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There are 13 Dictyostelium Src homology 2 (SH2) domain proteins, almost 10-fold fewer than in mammals, and only three are functionally unassigned. One of these, LrrB, contains a novel combination of protein interaction domains: an SH2 domain and a leucine-rich repeat domain. Growth and early development appear normal in the mutant, but expression profiling reveals that three genes active at these stages are greatly underexpressed: the ttdA metallohydrolase, the abcG10 small molecule transporter, and the cinB esterase.

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When cells are exposed to hyperosmotic stress, the Dictyostelium STAT orthologue STATc is rapidly tyrosine phosphorylated. Previous observations suggest a non-paradigmatic mode of STAT activation, whereby stress-induced serine phosphorylation of the PTP3 protein tyrosine phosphatase inhibits its activity towards STATc. We show that two serine residues in PTP3, S448 and S747, are rapidly phosphorylated after osmotic stress.

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The mature fruiting body of Dictyostelium consists of stalk and spore cells but its construction, and the migration of the preceding slug stage, requires a number of specialized sub-types of prestalk cell whose nature and function are not well understood. The prototypic prestalk-specific gene, ecmA, is inducible by the polyketide DIF-1 in a monolayer assay and requires the DimB and MybE transcription factors for full inducibility. We perform genome-wide microarray analyses, on parental, mybE- and dimB- cells, and identify many additional genes that depend on MybE and DimB for their DIF-1 inducibility.

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The tip of the Dictyostelium slug functions much like an embryonic organiser; when grafted onto the flank of a recipient slug, it recruits a mass of prespore cells and leads them away as part of a secondary slug. CudA is a nuclear protein which is expressed in prespore cells where it acts as a specific transcription factor. CudA is also expressed in an anteriorly located group of cells, the tip-organiser, that is believed to constitute the functional tip.

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Cbl proteins downregulate metazoan signalling pathways by ubiquitylating receptor tyrosine kinases, thereby targeting them for degradation. They contain a phosphotyrosine-binding region, comprising an EF-hand and an SH2 domain, linked to an E3 ubiquitin-ligase domain. CblA, a Dictyostelium homologue of the Cbl proteins, contains all three conserved domains.

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