Static stretching of the hamstring muscle for injury prevention in football codes: a systematic review

Purpose: Hamstring injuries are common among football players. There is still disagreement regarding prevention. The aim of this review is to determine whether static stretching reduces hamstring injuries in football codes. Methods: A systematic literature search was conducted on the online databases PubMed, PEDro, Cochrane, Web of Science, Bisp and Clinical Trial register. Study results were presented descriptively and the quality of the studies assessed were based on Cochrane’s ‘risk of bias’ tool. Results: The review identified 35 studies, including four analysis studies. These studies show deficiencies in the quality of study designs. Conclusion: The study protocols are varied in terms of the length of intervention and follow-up. No RCT studies are available, however, RCT studies should be conducted in the near future

Phocid Seal Leptin: Tertiary Structure and Hydrophobic Receptor Binding Site Preservation during Distinct Leptin Gene Evolution

The cytokine hormone leptin is a key signalling molecule in many pathways that control physiological functions. Although leptin demonstrates structural conservation in mammals, there is evidence of positive selection in primates, lagomorphs and chiropterans. We previously reported that the leptin genes of the grey and harbour seals (phocids) have significantly diverged from other mammals. Therefore we further investigated the diversification of leptin in phocids, other marine mammals and terrestrial taxa by sequencing the leptin genes of representative species. Phylogenetic reconstruction revealed that leptin diversification was pronounced within the phocid seals with a high dN/dS ratio of 2.8, indicating positive selection. We found significant evidence of positive selection along the branch leading to the phocids, within the phocid clade, but not over the dataset as a whole. Structural predictions indicate that the individual residues under selection are away from the leptin receptor (LEPR) binding site. Predictions of the surface electrostatic potential indicate that phocid seal leptin is notably different to other mammalian leptins, including the otariids. Cloning the grey seal leptin binding domain of LEPR confirmed that this was structurally conserved. These data, viewed in toto, support a hypothesis that phocid leptin divergence is unlikely to have arisen by random mutation. Based upon these phylogenetic and structural assessments, and considering the comparative physiology and varying life histories among species, we postulate that the unique phocid diving behaviour has produced this selection pressure. The Phocidae includes some of the deepest diving species, yet have the least modified lung structure to cope with pressure and volume changes experienced at depth. Therefore, greater surfactant production is required to facilitate rapid lung re-inflation upon surfacing, while maintaining patent airways. We suggest that this additional surfactant requirement is met by the leptin pulmonary surfactant production pathway which normally appears only to function in the mammalian foetus

Investigation of the Origin and Spread of a Mammalian Transposable Element Based on Current Sequence Diversity

Almost half the human genome consists of mobile DNA elements, and their analysis is a vital part of understanding the human genome as a whole. Many of these elements are ancient and have persisted in the genome for tens or hundreds of millions of years, providing a window into the evolution of modern mammals. The Golem family have been used as model transposons to highlight computational analyses which can be used to investigate these elements, particularly the use of molecular dating with large transposon families. Whole-genome searches found Golem sequences in 20 mammalian species. Golem A and B subsequences were only found in primates and squirrel. Interestingly, the full-length Golem, found as a few copies in many mammalian genomes, was found abundantly in horse. A phylogenetic profile suggested that Golem originated after the eutherian–metatherian divergence and that the A and B subfamilies originated at a much later date. Molecular dating based on sequence diversity suggests an early age, of 175 Mya, for the origin of the family and that the A and B lineages originated much earlier than expected from their current taxonomic distribution and have subsequently been lost in some lineages. Using publically available data, it is possible to investigate the evolutionary history of transposon families. Determining in which organisms a transposon can be found is often used to date the origin and expansion of the families. However, in this analysis, molecular dating, commonly used for determining the age of gene sequences, has been used, reducing the likelihood of errors from deleted lineages

Hyperdimensional Analysis of Amino Acid Pair Distributions in Proteins

Our manuscript presents a novel approach to protein structure analyses. We have organized an 8-dimensional data cube with protein 3D-structural information from 8706 high-resolution non-redundant protein-chains with the aim of identifying packing rules at the amino acid pair level. The cube contains information about amino acid type, solvent accessibility, spatial and sequence distance, secondary structure and sequence length. We are able to pose structural queries to the data cube using program ProPack. The response is a 1, 2 or 3D graph. Whereas the response is of a statistical nature, the user can obtain an instant list of all PDB-structures where such pair is found. The user may select a particular structure, which is displayed highlighting the pair in question. The user may pose millions of different queries and for each one he will receive the answer in a few seconds. In order to demonstrate the capabilities of the data cube as well as the programs, we have selected well known structural features, disulphide bridges and salt bridges, where we illustrate how the queries are posed, and how answers are given. Motifs involving cysteines such as disulphide bridges, zinc-fingers and iron-sulfur clusters are clearly identified and differentiated. ProPack also reveals that whereas pairs of Lys residues virtually never appear in close spatial proximity, pairs of Arg are abundant and appear at close spatial distance, contrasting the belief that electrostatic repulsion would prevent this juxtaposition and that Arg-Lys is perceived as a conservative mutation. The presented programs can find and visualize novel packing preferences in proteins structures allowing the user to unravel correlations between pairs of amino acids. The new tools allow the user to view statistical information and visualize instantly the structures that underpin the statistical information, which is far from trivial with most other SW tools for protein structure analysis

Endocytic regulation of alkali metal transport proteins in mammals, yeast and plants

The relative concentrations of ions and solutes inside cells are actively maintained by several classes of transport proteins, in many cases against their concentration gradient. These transport processes, which consume a large portion of cellular energy, must be constantly regulated. Many structurally distinct families of channels, carriers, and pumps have been characterized in considerable detail during the past decades and defects in the function of some of these proteins have been linked to a growing list of human diseases. The dynamic regulation of the transport proteins present at the cell surface is vital for both normal cellular function and for the successful adaptation to changing environments. The composition of proteins present at the cell surface is controlled on both the transcriptional and post-translational level. Post-translational regulation involves highly conserved mechanisms of phosphorylation- and ubiquitylation-dependent signal transduction routes used to modify the cohort of receptors and transport proteins present under any given circumstances. In this review, we will summarize what is currently known about one facet of this regulatory process: the endocytic regulation of alkali metal transport proteins. The physiological relevance, major contributors, parallels and missing pieces of the puzzle in mammals, yeast and plants will be discussed.This work was supported by grant BFU2011-30197-C03-03 from the Ministerio de Ciencia e Innovacion (Spain). V.L.-T. is supported by a fellowship from the Universidad Politecnica de Valencia. C. P. is supported by a fellowship from the Consejo Superior de Investigaciones Cientificas (Spain).Mulet Salort, JM.; Llopis Torregrosa, V.; Primo Planta, C.; Marques Romero, MC.; Yenush, L. (2013). Endocytic regulation of alkali metal transport proteins in mammals, yeast and plants. Current Genetics. 59(4):207-230. https://doi.org/10.1007/s00294-013-0401-2S207230594Abe F, Iida H (2003) Pressure-induced differential regulation of the two tryptophan permeases Tat1 and Tat2 by ubiquitin ligase Rsp5 and its binding proteins, Bul1 and Bul2. Mol Cell Biol 23:7566–7584Abriel H, Loffing J, Rebhun JF, Pratt JH, Schild L, Horisberger JD, Rotin D, Staub O (1999) Defective regulation of the epithelial Na+ channel by Nedd4 in Liddle’s syndrome. J Clin Invest 103:667–673. doi: 10.1172/JCI5713Alesutan I, Munoz C, Sopjani M, Dërmaku-Sopjani M, Michael D, Fraser S, Kemp BE, Seebohm G, Föller M, Lang F (2011) Inhibition of Kir2.1 (KCNJ2) by the AMP-activated protein kinase. Biochem Biophys Res Commun 408:505–510. doi: 10.1016/j.bbrc.2011.04.015Alvarez CE (2008) On the origins of arrestin and rhodopsin. BMC Evol Biol 8:222. doi: 10.1186/1471-2148-8-222Amerik AY, Nowak J, Swaminathan S, Hochstrasser M (2000) The Doa4 deubiquitinating enzyme is functionally linked to the vacuolar protein-sorting and endocytic pathways. Mol Biol Cell 11:3365–3380Anderson JA, Huprikar SS, Kochian LV, Lucas WJ, Gaber RF (1992) Functional expression of a probable Arabidopsis thaliana potassium channel in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 89:3736–3740Anderson JA, Nakamura RL, Gaber RF (1994) Heterologous expression of K+ channels in Saccharomyces cerevisiae: strategies for molecular analysis of structure and function. Symp Soc Exp Biol 48:85–97Aniento F, Gu F, Parton RG, Gruenberg J (1996) An endosomal beta COP is involved in the pH-dependent formation of transport vesicles destined for late endosomes. J Cell Biol 133:29–41Apse MP, Aharon GS, Snedden WA, Blumwald E (1999) Salt tolerance conferred by overexpression of a vacuolar Na+/H+ antiport in Arabidopsis. Science 285:1256–1258Arino J, Ramos J, Sychrova H (2010) Alkali metal cation transport and homeostasis in yeasts. Microbiol mol biol rev 74:95–120. doi: 10.1128/mmbr.00042-09Arnason TG, Pisclevich MG, Dash MD, Davies GF, Harkness TA (2005) Novel interaction between Apc5p and Rsp5p in an intracellular signaling pathway in Saccharomyces cerevisiae. Eukaryot Cell 4:134–146. doi: 10.1128/EC.4.1.134-146.2005Arroyo JP, Lagnaz D, Ronzaud C, Vázquez N, Ko BS, Moddes L, Ruffieux-Daidié D, Hausel P, Koesters R, Yang B, Stokes JB, Hoover RS, Gamba G, Staub O (2011) Nedd4-2 modulates renal Na+ –Cl– cotransporter via the aldosterone-SGK1-Nedd4-2 pathway. J Am Soc Nephrol 22:1707–1719. doi: 10.1681/ASN.2011020132Azmi IF, Davies BA, Xiao J, Babst M, Xu Z, Katzmann DJ (2008) ESCRT-III family members stimulate Vps4 ATPase activity directly or via Vta1. Dev Cell 14:50–61. doi: 10.1016/j.devcel.2007.10.021Babst M, Katzmann DJ, Estepa-Sabal EJ, Meerloo T, Emr SD (2002a) Escrt-III: an endosome-associated heterooligomeric protein complex required for mvb sorting. Dev Cell 3:271–282Babst M, Katzmann DJ, Snyder WB, Wendland B, Emr SD (2002b) Endosome-associated complex, ESCRT-II, recruits transport machinery for protein sorting at the multivesicular body. Dev Cell 3:283–289Bache KG, Slagsvold T, Cabezas A, Rosendal KR, Raiborg C, Stenmark H (2004) The growth-regulatory protein HCRP1/hVps37A is a subunit of mammalian ESCRT-I and mediates receptor down-regulation. Mol Biol Cell 15:4337–4346. doi: 10.1091/mbc.E04-03-0250Baietti MF, Zhang Z, Mortier E, Melchior A, Degeest G, Geeraerts A, Ivarsson Y, Depoortere F, Coomans C, Vermeiren E, Zimmermann P, David G (2012) Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat Cell Biol 14:677–685. doi: 10.1038/ncb2502Barajas D, Nagy PD (2010) Ubiquitination of tombusvirus p33 replication protein plays a role in virus replication and binding to the host Vps23p ESCRT protein. Virology 397:358–368. doi: 10.1016/j.virol.2009.11.010Barajas D, Jiang Y, Nagy PD (2009) A unique role for the host ESCRT proteins in replication of Tomato bushy stunt virus. PLoS Pathog 5:e1000705. doi: 10.1371/journal.ppat.1000705Barberon M, Zelazny E, Robert S, Conéjéro G, Curie C, Friml J, Vert G (2011) Monoubiquitin-dependent endocytosis of the iron-regulated transporter 1 (IRT1) transporter controls iron uptake in plants. Proc Natl Acad Sci USA 108:E450–E458. doi: 10.1073/pnas.1100659108Barragán V, Leidi EO, Andrés Z, Rubio L, De Luca A, Fernández JA, Cubero B, Pardo JM (2012) Ion exchangers NHX1 and NHX2 mediate active potassium uptake into vacuoles to regulate cell turgor and stomatal function in Arabidopsis. Plant Cell 24:1127–1142. doi: 10.1105/tpc.111.095273Bassil E, Ohto MA, Esumi T, Tajima H, Zhu Z, Cagnac O, Belmonte M, Peleg Z, Yamaguchi T, Blumwald E (2011) The Arabidopsis intracellular Na+/H+ antiporters NHX5 and NHX6 are endosome associated and necessary for plant growth and development. Plant Cell 23:224–239. doi: 10.1105/tpc.110.079426Beaudenon SL, Huacani MR, Wang G, McDonnell DP, Huibregtse JM (1999) Rsp5 ubiquitin-protein ligase mediates DNA damage-induced degradation of the large subunit of RNA polymerase II in Saccharomyces cerevisiae. Mol Cell Biol 19:6972–6979Becuwe M, Vieira N, Lara D, Gomes-Rezende J, Soares-Cunha C, Casal M, Haguenauer-Tsapis R, Vincent O, Paiva S, Léon S (2012) A molecular switch on an arrestin-like protein relays glucose signaling to transporter endocytosis. J Cell Biol 196:247–259. doi: 10.1083/jcb.201109113Belgareh-Touzé N, Léon S, Erpapazoglou Z, Stawiecka-Mirota M, Urban-Grimal D, Haguenauer-Tsapis R (2008) Versatile role of the yeast ubiquitin ligase Rsp5p in intracellular trafficking. Biochem Soc Trans 36:791–796. doi: 10.1042/BST0360791Bhalla V, Oyster NM, Fitch AC, Wijngaarden MA, Neumann D, Schlattner U, Pearce D, Hallows KR (2006) AMP-activated kinase inhibits the epithelial Na+ channel through functional regulation of the ubiquitin ligase Nedd4-2. J Biol Chem 281:26159–26169. doi: 10.1074/jbc.M606045200Blondel MO, Morvan J, Dupre S, Urban-Grimal D, Haguenauer-Tsapis R, Volland C (2004) Direct sorting of the yeast uracil permease to the endosomal system is controlled by uracil binding and Rsp5p-dependent ubiquitylation. Mol Biol Cell 15:883–895. doi: 10.1091/mbc.E03-04-0202Boase NA, Rychkov GY, Townley SL, Dinudom A, Candi E, Voss AK, Tsoutsman T, Semsarian C, Melino G, Koentgen F, Cook DI, Kumar S (2011) Respiratory distress and perinatal lethality in Nedd4-2-deficient mice. Nat Commun 2:287. doi: 10.1038/ncomms1284Boehmer C, Laufer J, Jeyaraj S, Klaus F, Lindner R, Lang F, Palmada M (2008) Modulation of the voltage-gated potassium channel Kv1.5 by the SGK1 protein kinase involves inhibition of channel ubiquitination. Cell Physiol Biochem 22:591–600. doi: 10.1159/000185543Bonifacino JS, Traub LM (2003) Signals for sorting of transmembrane proteins to endosomes and lysosomes. Annu Rev Biochem 72:395–447. doi: 10.1146/annurev.biochem.72.121801.161800Bowers K, Levi BP, Patel FI, Stevens TH (2000) The sodium/proton exchanger Nhx1p is required for endosomal protein trafficking in the yeast Saccharomyces cerevisiae. Mol Biol Cell 11:4277–4294Brett CL, Tukaye DN, Mukherjee S, Rao R (2005) The yeast endosomal Na+K+/H+ exchanger Nhx1 regulates cellular pH to control vesicle trafficking. Mol Biol Cell 16:1396–1405. doi: 10.1091/mbc.E04-11-0999Cao XR, Lill NL, Boase N, Shi PP, Croucher DR, Shan H, Qu J, Sweezer EM, Place T, Kirby PA, Daly RJ, Kumar S, Yang B (2008) Nedd4 controls animal growth by regulating IGF-1 signaling. Sci Signal 1:ra5. doi: 10.1126/scisignal.1160940Carrasquillo R, Tian D, Krishna S, Pollak MR, Greka A, Schlöndorff J (2012) SNF8, a member of the ESCRT-II complex, interacts with TRPC6 and enhances its channel activity. BMC Cell Biol 13:33. doi: 10.1186/1471-2121-13-33Chen L, Hellmann H (2013) Plant E3 Ligases: flexible enzymes in a sessile world1. Mol Plant. doi: 10.1093/mp/sst005Chinchilla D, Zipfel C, Robatzek S, Kemmerling B, Nürnberger T, Jones JD, Felix G, Boller T (2007) A flagellin-induced complex of the receptor FLS2 and BAK1 initiates plant defence. Nature 448:497–500. doi: 10.1038/nature05999Christie KJ, Martinez JA, Zochodne DW (2012) Disruption of E3 ligase NEDD4 in peripheral neurons interrupts axon outgrowth: linkage to PTEN. Mol Cell Neurosci 50:179–192. doi: 10.1016/j.mcn.2012.04.006Clague MJ, Liu H, Urbé S (2012) Governance of endocytic trafficking and signaling by reversible ubiquitylation. Dev Cell 23:457–467. doi: 10.1016/j.devcel.2012.08.011Clancy JL, Henderson MJ, Russell AJ, Anderson DW, Bova RJ, Campbell IG, Choong DY, Macdonald GA, Mann GJ, Nolan T, Brady G, Olopade OI, Woollatt E, Davies MJ, Segara D, Hacker NF, Henshall SM, Sutherland RL, Watts CK (2003) EDD, the human orthologue of the hyperplastic discs tumour suppressor gene, is amplified and overexpressed in cancer. Oncogene 22:5070–5081. doi: 10.1038/sj.onc.1206775Coonrod EM, Stevens TH (2010) The yeast vps class E mutants: the beginning of the molecular genetic analysis of multivesicular body biogenesis. Mol Biol Cell 21:4057–4060. doi: 10.1091/mbc.E09-07-0603Crespo JL, Daicho K, Ushimaru T, Hall MN (2001) The GATA transcription factors GLN3 and GAT1 link TOR to salt stress in Saccharomyces cerevisiae. J Biol Chem 276:34441–34444. doi: 10.1074/jbc.M103601200Debonneville C, Flores SY, Kamynina E, Plant PJ, Tauxe C, Thomas MA, Münster C, Chraïbi A, Pratt JH, Horisberger JD, Pearce D, Loffing J, Staub O (2001) Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression. EMBO J 20:7052–7059. doi: 10.1093/emboj/20.24.7052Downes BP, Stupar RM, Gingerich DJ, Vierstra RD (2003) The HECT ubiquitin-protein ligase (UPL) family in Arabidopsis: UPL3 has a specific role in trichome development. Plant J 35:729–742Eisenach C, Chen ZH, Grefen C, Blatt MR (2012) The trafficking protein SYP121 of Arabidopsis connects programmed stomatal closure and K+ channel activity with vegetative growth. Plant J 69:241–251. doi: 10.1111/j.1365-313X.2011.04786.xEkberg J, Schuetz F, Boase NA, Conroy SJ, Manning J, Kumar S, Poronnik P, Adams DJ (2007) Regulation of the voltage-gated K(+) channels KCNQ2/3 and KCNQ3/5 by ubiquitination. Novel role for Nedd4-2. J Biol Chem 282:12135–12142. doi: 10.1074/jbc.M609385200Faresse N, Lagnaz D, Debonneville A, Ismailji A, Maillard M, Fejes-Toth G, Náray-Fejes-Tóth A, Staub O (2012) Inducible kidney-specific Sgk1 knockout mice show a salt-losing phenotype. Am J Physiol Renal Physiol 302:F977–F985. doi: 10.1152/ajprenal.00535.2011Field MC, Gabernet-Castello C, Dacks JB (2007) Reconstructing the evolution of the endocytic system: insights from genomics and molecular cell biology. Adv Exp Med Biol 607:84–96. doi: 10.1007/978-0-387-74021-8_7Fisk HA, Yaffe MP (1999) A role for ubiquitination in mitochondrial inheritance in Saccharomyces cerevisiae. J Cell Biol 145:1199–1208Flinn RJ, Yan Y, Goswami S, Parker PJ, Backer JM (2010) The late endosome is essential for mTORC1 signaling. Mol Biol Cell 21:833–841. doi: 10.1091/mbc.E09-09-0756Fotia AB, Ekberg J, Adams DJ, Cook DI, Poronnik P, Kumar S (2004) Regulation of neuronal voltage-gated sodium channels by the ubiquitin-protein ligases Nedd4 and Nedd4-2. J Biol Chem 279:28930–28935. doi: 10.1074/jbc.M402820200Futter CE, White IJ (2007) Annexins and endocytosis. Traffic 8:951–958. doi: 10.1111/j.1600-0854.2007.00590.xGabriely G, Kama R, Gerst JE (2007) Involvement of specific COPI subunits in protein sorting from the late endosome to the vacuole in yeast. Mol Cell Biol 27:526–540. doi: 10.1128/MCB.00577-06Gajewska B, Shcherbik N, Oficjalska D, Haines DS, Zoladek T (2003) Functional analysis of the human orthologue of the RSP5-encoded ubiquitin protein ligase, hNedd4, in yeast. Curr Genet 43:1–10. doi: 10.1007/s00294-003-0371-xGalan JM, Moreau V, Andre B, Volland C, Haguenauer-Tsapis R (1996) Ubiquitination mediated by the Npi1p/Rsp5p ubiquitin-protein ligase is required for endocytosis of the yeast uracil permease. J Biol Chem 271:10946–10952Gao T, Liu Z, Wang Y, Cheng H, Yang Q, Guo A, Ren J, Xue Y (2013) UUCD: a family-based database of ubiquitin and ubiquitin-like conjugation. Nucleic Acids Res 41:D445–D451. doi: 10.1093/nar/gks1103Geldner N (2004) The plant endosomal system—its structure and role in signal transduction and plant development. Planta 219:547–560. doi: 10.1007/s00425-004-1302-xGitan RS, Eide DJ (2000) Zinc-regulated ubiquitin conjugation signals endocytosis of the yeast ZRT1 zinc transporter. Biochem J 346:329–336. doi: 10.1042/0264-6021:3460329Gitan RS, Luo H, Rodgers J, Broderius M, Eide D (1998) Zinc-induced inactivation of the yeast ZRT1 zinc transporter occurs through endocytosis and vacuolar degradation. J Biol Chem 273:28617–28624Gómez-Gómez L, Boller T (2000) FLS2: an LRR receptor-like kinase involved in the perception of the bacterial elicitor flagellin in Arabidopsis. Mol Cell 5:1003–1011Gong X, Chang A (2001) A mutant plasma membrane ATPase, Pma1-10, is defective in stability at the yeast cell surface. Proc Natl Acad Sci USA 98:9104–9109. doi: 10.1073/pnas.161282998Guo J, Wang T, Li X, Shallow H, Yang T, Li W, Xu J, Fridman MD, Yang X, Zhang S (2012) Cell surface expression of human ether-a-go–go-related gene (hERG) channels is regulated by caveolin-3 protein via the ubiquitin ligase Nedd4-2. J Biol Chem 287:33132–33141. doi: 10.1074/jbc.M112.389643Gwizdek C, Hobeika M, Kus B, Ossareh-Nazari B, Dargemont C, Rodriguez MS (2005) The mRNA nuclear export factor Hpr1 is regulated by Rsp5-mediated ubiquitylation. J Biol Chem 280:13401–13405. doi: 10.1074/jbc.C500040200Haas TJ, Sliwinski MK, Martínez DE, Preuss M, Ebine K, Ueda T, Nielsen E, Odorizzi G, Otegui MS (2007) The Arabidopsis AAA ATPase SKD1 is involved in multivesicular endosome function and interacts with its positive regulator LYST-INTERACTING PROTEIN5. Plant Cell 19:1295–1312. doi: 10.1105/tpc.106.049346Harkness TA, Davies GF, Ramaswamy V, Arnason TG (2002) The ubiquitin-dependent targeting pathway in Saccharomyces cerevisiae plays a critical role in multiple chromatin assembly regulatory steps. Genetics 162:615–632Hasenbrink G, Schwarzer S, Kolacna L, Ludwig J, Sychrova H, Lichtenberg-Fraté H (2005) Analysis of the mKir2.1 channel activity in potassium influx defective Saccharomyces cerevisiae strains determined as changes in growth characteristics. FEBS Lett 579:1723–1731. doi: 10.1016/j.febslet.2005.02.025Hatakeyama R, Kamiya M, Takahara T, Maeda T (2010) Endocytosis of the aspartic acid/glutamic acid transporter Dip5 is triggered by substrate-dependent recruitment of the Rsp5 ubiquitin ligase via the arrestin-like protein Aly2. Mol Cell Biol 30:5598–5607. doi: 10.1128/MCB.00464-10Hayashi M, Fukuzawa T, Sorimachi H, Maeda T (2005) Constitutive activation of the pH-responsive Rim101 pathway in yeast mutants defective in late steps of the MVB/ESCRT pathway. Mol Cell Biol 25:9478–9490. doi: 10.1128/mcb.25.21.9478-9490.2005He P, Lee SJ, Lin S, Seidler U, Lang F, Fejes-Toth G, Naray-Fejes-Toth A, Yun CC (2011) Serum- and glucocorticoid-induced kinase 3 in recycling endosomes mediates acute activation of Na+/H+ exchanger NHE3 by glucocorticoids. Mol Biol Cell 22:3812–3825. doi: 10.1091/mbc.E11-04-0328Heese A, Hann DR, Gimenez-Ibanez S, Jones AM, He K, Li J, Schroeder JI, Peck SC, Rathjen JP (2007) The receptor-like kinase SERK3/BAK1 is a central regulator of innate immunity in plants. Proc Natl Acad Sci USA 104:12217–12222. doi: 10.1073/pnas.0705306104Hein C, Springael JY, Volland C, Haguenauer-Tsapis R, André B (1995) NPl1, an essential yeast gene involved in induced degradation of Gap1 and Fur4 permeases, encodes the Rsp5 ubiquitin-protein ligase. Mol Microbiol 18:77–87Henke G, Maier G, Wallisch S, Boehmer C, Lang F (2004) Regulation of the voltage gated K+ channel Kv1.3 by the ubiquitin ligase Nedd4-2 and the serum and glucocorticoid inducible kinase SGK1. J Cell Physiol 199:194–199. doi: 10.1002/jcp.10430Herberth S, Shahriari M, Bruderek M, Hessner F, Müller B, Hülskamp M, Schellmann S (2012) Artificial ubiquitylation is sufficient for sorting of a plasma membrane ATPase to the vacuolar lumen of Arabidopsis cells. Planta 236:63–77. doi: 10.1007/s00425-012-1587-0Hicke L, Dunn R (2003) Regulation of membrane protein transport by ubiquitin and ubiquitin-binding proteins. Annu Rev Cell Dev Biol 19:141–172. doi: 10.1146/annurev.cellbio.19.110701.154617Hicke L, Riezman H (1996) Ubiquitination of a yeast plasma membrane receptor signals its ligand-stimulated endocytosis. Cell 84:277–287Hicke L, Zanolari B, Riezman H (1998) Cytoplasmic tail phosphorylation of the alpha-factor receptor is required for its ubiquitination and internalization. J Cell Biol 141:349–358Hoppe T, Matuschewski K, Rape M, Schlenker S, Ulrich HD, Jentsch S (2000) Activation of a membrane-bound transcription factor by regulated ubiquitin/proteasome-dependent processing. Cell 102:577–586Hsu C, Morohashi Y, Yoshimura S, Manrique-Hoyos N, Jung S, Lauterbach MA, Bakhti M, Grønborg M, Möbius W, Rhee J, Barr FA, Simons M (2010) Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A-C. J Cell Biol 189:223–232. doi: 10.1083/jcb.200911018Hu G, Caza M, Cadieux B, Chan V, Liu V, Kronstad J (2013) Cryptococcus neoformans requires the ESCRT protein Vps23 for iron acquisition from heme, for capsule formation, and for virulence. Infect Immun 81:292–302. doi: 10.1128/IAI.01037-12Huang F, Kirkpatrick D, Jiang X, Gygi S, Sorkin A (2006) Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain. Mol Cell 21:737–748. doi: 10.1016/j.molcel.2006.02.018Huang F, Goh LK, Sorkin A (2007) EGF receptor ubiquitination is not necessary for its internalization. Proc Natl Acad Sci USA 104:16904–16909. doi: 10.1073/pnas.0707416104Huibregtse JM, Scheffner M, Beaudenon S, Howley PM (1995) A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase. Proc Natl Acad Sci USA 92:2563–2567Hurst AC, Meckel T, Tayefeh S, Thiel G, Homann U (2004) Trafficking of the plant potassium inward rectifier KAT1 in guard cell protoplasts of Vicia faba. Plant J 37:391–397Husnjak K, Dikic I (2012) Ubiquitin-binding proteins: decoders of ubiquitin-mediated cellular functions. Annu Rev Biochem 81:291–322. doi: 10.1146/annurev-biochem-051810-094654Ibl V, Csaszar E, Schlager N, Neubert S, Spitzer C, Hauser MT (2012) Interactome of the plant-specific ESCRT-III component AtVPS2.2 in Arabidopsis thaliana. J Proteome Res 11:397–411. doi: 10.1021/pr200845nIchimura T, Yamamura H, Sasamoto K, Tominaga Y, Taoka M, Kakiuchi K, Shinkawa T, Takahashi N, Shimada S, Isobe T (2005) 14-3-3 proteins modulate the expression of epithelial Na + channels by phosphorylation-dependent interaction with Nedd4-2 ubiquitin ligase. J Biol Chem 280:13187–13194. doi: 10.1074/jbc.M412884200Jegla TJ, Zmasek CM, Batalov S, Nayak SK (2009) Evolution of the human ion channel set. Comb Chem High Throughput Screen 12:2–23Jenness DD, Li Y, Tipper C, Spatrick P (1997) Elimination of defective alpha-factor pheromone receptors. Mol Cell Biol 17:6236–6245Jespersen T, Membrez M, Nicolas CS, Pitard B, Staub O, Olesen SP, Baró I, Abriel H (2007) The KCNQ1 potassium channel is down-regulated by ubiquitylating enzymes of the Nedd4/Nedd4-like family. Cardiovasc Res 74:64–74. doi: 10.1016/j.cardiores.2007.01.008Jolliffe CN, Harvey KF, Haines BP, Parasivam G, Kumar S (2000) Identification of multiple proteins expressed in murine embryos as binding partners for the WW domains of the ubiquitin-protein ligase Nedd4. Biochem J 351(Pt 3):557–565Kallay LM, Brett CL, Tukaye DN, Wemmer MA, Chyou A, Odorizzi G, Rao R (2011) Endosomal Na+(K+)/H+ exchanger Nhx1/Vps44 functions independently and downstream of multivesicular body formation. J Biol Chem 286:44067–44077. doi: 10.1074/jbc.M111.282319Kamsteeg EJ, Savelkoul PJ, Hendriks G, Konings IB, Nivillac NM, Lagendijk AK, van der Sluijs P, Deen PM (2008) Missorting of the Aquaporin-2 mutant E258K to multivesicular bodies/lysosomes in dominant NDI is associated with its monoubiquitination and increased phosphoryla

A supermatrix analysis of genomic, morphological, and paleontological data from crown Cetacea

<p>Abstract</p> <p>Background</p> <p>Cetacea (dolphins, porpoises, and whales) is a clade of aquatic species that includes the most massive, deepest diving, and largest brained mammals. Understanding the temporal pattern of diversification in the group as well as the evolution of cetacean anatomy and behavior requires a robust and well-resolved phylogenetic hypothesis. Although a large body of molecular data has accumulated over the past 20 years, DNA sequences of cetaceans have not been directly integrated with the rich, cetacean fossil record to reconcile discrepancies among molecular and morphological characters.</p> <p>Results</p> <p>We combined new nuclear DNA sequences, including segments of six genes (~2800 basepairs) from the functionally extinct Yangtze River dolphin, with an expanded morphological matrix and published genomic data. Diverse analyses of these data resolved the relationships of 74 taxa that represent all extant families and 11 extinct families of Cetacea. The resulting supermatrix (61,155 characters) and its sub-partitions were analyzed using parsimony methods. Bayesian and maximum likelihood (ML) searches were conducted on the molecular partition, and a molecular scaffold obtained from these searches was used to constrain a parsimony search of the morphological partition. Based on analysis of the supermatrix and model-based analyses of the molecular partition, we found overwhelming support for 15 extant clades. When extinct taxa are included, we recovered trees that are significantly correlated with the fossil record. These trees were used to reconstruct the timing of cetacean diversification and the evolution of characters shared by "river dolphins," a non-monophyletic set of species according to all of our phylogenetic analyses.</p> <p>Conclusions</p> <p>The parsimony analysis of the supermatrix and the analysis of morphology constrained to fit the ML/Bayesian molecular tree yielded broadly congruent phylogenetic hypotheses. In trees from both analyses, all Oligocene taxa included in our study fell outside crown Mysticeti and crown Odontoceti, suggesting that these two clades radiated in the late Oligocene or later, contra some recent molecular clock studies. Our trees also imply that many character states shared by river dolphins evolved in their oceanic ancestors, contradicting the hypothesis that these characters are convergent adaptations to fluvial habitats.</p

Movement Patterns and Muscular Function Before and After Onset of Sports-Related Groin Pain: A Systematic Review with Meta-analysis

BACKGROUND: Sports-related groin pain (SRGP) is a common entity in rotational sports such as football, rugby and hockey, accounting for 12-18 % of injuries each year, with high recurrence rates and often prolonged time away from sport. OBJECTIVE: This systematic review synthesises movement and muscle function findings to better understand deficits and guide rehabilitation. STUDY SELECTION: Prospective and retrospective cross-sectional studies investigating muscle strength, flexibility, cross-sectional area, electromyographic activation onset and magnitude in patients with SRGP were included. SEARCH METHODS: Four databases (MEDLINE, Web of Knowledge, EBSCOhost and EMBASE) were searched in June 2014. Studies were critiqued using a modified version of the Downs and Black Quality Index, and a meta-analysis was performed. RESULTS: Seventeen studies (14 high quality, 3 low quality; 8 prospective and 9 retrospective) were identified. Prospective findings: moderate evidence indicated decreased hip abduction flexibility as a risk factor for SRGP. Limited or very limited evidence suggested that decreased hip adduction strength during isokinetic testing at ~119°/s was a risk factor for SRGP, but no associations were found at ~30°/s or ~210°/s, or with peak torque angle. Decreased hip abductor strength in angular velocity in ~30°/s but not in ~119°/s and ~210°/s was found as a risk factor for SRGP. No relationships were found with hip internal or external rotation range of movement, nor isokinetic knee extension strength. Decreased isokinetic knee flexion strength also was a potential risk factor for SRGP, at a speed ~60°/s. Retrospective findings: there was strong evidence of decreased hip adductor muscle strength during a squeeze test at 45°, and decreased total hip external rotation range of movement (sum of both legs) being associated with SRGP. There was strong evidence of no relationship to abductor muscle strength nor unilateral hip internal and external rotation range of movement. Moderate evidence suggested that increased abduction flexibility and no change in total hip internal rotation range of movement (sum of both legs) were retrospectively associated with SRGP. Limited or very limited evidence (significant findings only) indicated decreased hip adductor muscle strength during 0° and 30° squeeze tests and during an eccentric hip adduction test, but a decrease in the isometric adductors-to-abductors strength ratio at speed 120°/s; decreased abductors-to-adductors activation ratio in the early phase in the moving leg as well as in all three phases in the weight-bearing leg during standing hip flexion; and increased hip flexors strength during isokinetic and decrease in transversus abdominis muscle resting thickness associated with SRGP. CONCLUSIONS: There were a number of significant movement and muscle function associations observed in athletes both prior to and following the onset of SRGP. The strength of findings was hampered by the lack of consistent terminology and diagnostic criteria, with there being clear guides for future research. Nonetheless, these findings should be considered in rehabilitation and prevention planning