A COMPARISON OF TWO BACKSTROKE STARTS

This study investigated the effect of a staggered or parallel foot placement on horizontal distance and velocity at which the swimmer moved away from the block to the point that the hands entered the water during a backstroke start. Ten NCAA division II collegiate women swimmers were filmed from above water performing three of each of the two types of starts. An underwater camera was used to capture stability aspects of the feet prior to and during the start. There was no significant difference (p > 0.05) seen in average velocity or horizontal distance that the swimmer traveled when comparing both types of starts. The Chi squared analysis found no significant differences in movement of the feet during the two backstroke starts (p > 0.05). Further research should be performed with increased practice time of both starts and to compare differences between genders

Leucophoropterini

159 p. : ill. (some col.), maps ; 26 cm.The Leucophoropterini (Miridae: Phylinae) is an Indo-Australian group including 23 genera and 104 species. Diagnoses are provided for all genera of Leucophoropterini. All genera and species of Australian fauna are revised and redescribed to complement earlier detailed study of Schuh for the Indo-Pacific fauna. Additional new taxa from Papua New Guinea are described and a key to the currently recognized genera is provided, as are keys to the species of Ausejanus, n. gen., and Blesingia Carvalho and Gross. Previously described genera include: Abuyogocoris Schuh (4 species), Aitkenia Carvalho and Gross (2 species, 1 described as new), Arafuramiris Schuh (7 species, 3 described as new), Biromiris Schuh (6 species, 3 described as new), Blesingia Carvalho and Gross (7 species, 5 as new combinations), Collessicoris Carvalho and Gross (1 species), Ctypomiris Schuh (3 species, 1 described as new), Gulacapsus Schuh (4 species, 1 described as new), Leucophoroptera Poppius (5 species, 2 described as new), Papuamimus Schuh (2 species), Pseudohallodapocoris Schuh (3 species), Sejanus Distant (29 species), Solomonomimus Schuh (1 species), Trichocephalocapsus Schuh (2 species), and Waterhouseana Carvalho (2 species, 1 described as new) are revised. New genera include: Ausejanus (18 species, 7 described as new and 11 as new combinations), Austrodapus (1 species, described as new), Johnstonsonius (1 species, described as new), Missanos (1 species, described as new), Neaitkenia (2 species, new combinations), Neoleucophoroptera (2 species, new combinations), Papuamiroides (1 species, described as new), and Transleucophoroptera (1 species, new combination). Pseudoleucophoroptera Schuh is synonymized with Blesingia Carvalho and Gross. The following species synonymies are created (junior synonyms first): Sejanus brunneus Carvalho and Gross = Ausejanus tasmaniae (Carvalho and Gross), Sejanus intermedius Carvalho and Gross = Ausejanus albisignatus (Knight), Sejanus melaleucae Carvalho and Gross = Ausejanus mcdonaldi (Carvalho and Gross), Sejanus rosei Carvalho and Gross = Sejanus palumae Carvalho and Gross, and Leucophoroptera nitidior Carvalho and Gross = Blesingia elegans Carvalho and Gross 5 Blesingia latezonata Carvalho and Gross = Leucophoroptera quadrimaculata Poppius. The genera Dilatops Weirauch, Karoocapsus Schuh, Lasiolabops Poppius, Myrmicopsella Poppius, Porophoroptera Carvalho and Gross, Schuhistes Menard, and Tytthus Fieber are removed from the Leucophoropterini. Sejanus species S. biniguni Schuh, S. fasciatus Carvalho and Gross, S. fijiensis Schuh, S. hongkong Schuh, S. leai Carvalho and Gross, S. novecaledonicus Schuh, S. occidentalis Carvalho and Gross, S. ruber Carvalho and Gross, S. rubricatus Carvalho and Gross, and S. trivinosus Carvalho and Gross are treated as incertae sedis

Committing to ecological restoration: Efforts around the globe need legal and policy clarification

At the September 2014 United Nations Climate Summit, governments rallied around an international agreement—the New York Declaration on Forests—that underscored restoration of degraded ecosystems as an auspicious solution to climate change. Ethiopia committed to restore more than one-sixth of its land. Uganda, the Democratic Republic of Congo, Guatemala, and Colombia pledged to restore huge areas within their borders. In total, parties committed to restore a staggering 350 million hectares by 2030.Fil: Suding, Kathering. State University Of Colorado-boulder; Estados UnidosFil: Higgs, Eric. University Of Victoria; CanadáFil: Palmer, Margaret. University of Maryland; Estados UnidosFil: Callicott, J. Baird. University Of North Texas; Estados UnidosFil: Anderson, Christopher Brian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; ArgentinaFil: Baker, Matthew. University Of Maryland; Estados UnidosFil: Gutrich, John J.. Southern Oregon University; Estados UnidosFil: Hondula, Kelly L.. University of Maryland; Estados UnidosFil: Lafevor, Matthew C.. University of Maryland; Estados UnidosFil: Larson, Brendon M. H.. University Of Waterloo; CanadáFil: Randall, Alan. Ohio State University; Estados Unidos. University Of Sidney; AustraliaFil: Ruhl, J. B.. Vanderbilt University; Estados UnidosFil: Schwartz, Katrina Z. S.. Woodrow Wilson International Center for Scholars; Estados Unido

A DOCK8-WIP-WASp complex links T cell receptors to the actin cytoskeleton

Wiskott-Aldrich syndrome (WAS) is associated with mutations in the WAS protein (WASp), which plays a critical role in the initiation of T cell receptor–driven (TCR-driven) actin polymerization. The clinical phenotype of WAS includes susceptibility to infection, allergy, autoimmunity, and malignancy and overlaps with the symptoms of dedicator of cytokinesis 8 (DOCK8) deficiency, suggesting that the 2 syndromes share common pathogenic mechanisms. Here, we demonstrated that the WASp-interacting protein (WIP) bridges DOCK8 to WASp and actin in T cells. We determined that the guanine nucleotide exchange factor activity of DOCK8 is essential for the integrity of the subcortical actin cytoskeleton as well as for TCR-driven WASp activation, F-actin assembly, immune synapse formation, actin foci formation, mechanotransduction, T cell transendothelial migration, and homing to lymph nodes, all of which also depend on WASp. These results indicate that DOCK8 and WASp are in the same signaling pathway that links TCRs to the actin cytoskeleton in TCR-driven actin assembly. Further, they provide an explanation for similarities in the clinical phenotypes of WAS and DOCK8 deficiency.United States. Public Health Service (RO1AI114588)United States. Public Health Service (K08AI114968

Protection from EAE in DOCK8 mutant mice occurs despite increased Th17 cell frequencies in the periphery.

peer reviewedMutation of Dedicator of cytokinesis 8 (DOCK8) has previously been reported to provide resistance to the Th17 cell dependent EAE in mice. Contrary to expectation, we observed an elevation of Th17 cells in two different DOCK8 mutant mouse strains in the steady state. This was specific for Th17 cells with no change in Th1 or Th2 cell populations. In vitro Th cell differentiation assays revealed that the elevated Th17 cell population was not due to a T cell intrinsic differentiation bias. Challenging these mutant mice in the EAE model, we confirmed a resistance to this autoimmune disease with Th17 cells remaining elevated systemically while cellular infiltration in the CNS was reduced. Infiltrating T cells lost the bias toward Th17 cells indicating a relative reduction of Th17 cells in the CNS and a Th17 cell specific migration disadvantage. Adoptive transfers of Th1 and Th17 cells in EAE-affected mice further supported the Th17 cell-specific migration defect, however, DOCK8-deficient Th17 cells expressed normal Th17 cell-specific CCR6 levels and migrated toward chemokine gradients in transwell assays. This study shows that resistance to EAE in DOCK8 mutant mice is achieved despite a systemic Th17 bias

4 '-Phosphopantetheine corrects CoA, iron, and dopamine metabolic defects in mammalian models of PKAN

Pantothenate kinase-associated neurodegeneration (PKAN) is an inborn error of CoA metabolism causing dystonia, parkinsonism, and brain iron accumulation. Lack of a good mammalian model has impeded studies of pathogenesis and development of rational therapeutics. We took a new approach to investigating an existing mouse mutant of Pank2 and found that isolating the disease-vulnerable brain revealed regional perturbations in CoA metabolism, iron homeostasis, and dopamine metabolism and functional defects in complex I and pyruvate dehydrogenase. Feeding mice a CoA pathway intermediate, 4 '-phosphopantetheine, normalized levels of the CoA-, iron-, and dopamine-related biomarkers as well as activities of mitochondrial enzymes. Human cell changes also were recovered by 4 '-phosphopantetheine. We can mechanistically link a defect in CoA metabolism to these secondary effects via the activation of mitochondrial acyl carrier protein, which is essential to oxidative phosphorylation, iron-sulfur cluster biogenesis, and mitochondrial fatty acid synthesis. We demonstrate the fidelity of our model in recapitulating features of the human disease. Moreover, we identify pharmacodynamic biomarkers, provide insights into disease pathogenesis, and offer evidence for 4 '-phosphopantetheine as a candidate therapeutic for PKAN

Rasgrp1 mutation increases naïve T-cell CD44 expression and drives mTOR-dependent accumulation of Helios+ T cells and autoantibodies

Missense variants are a major source of human genetic variation. Here we analyze a new mouse missense variant, Rasgrp1Anaef, with an ENU-mutated EF hand in the Rasgrp1 Ras guanine nucleotide exchange factor. Rasgrp1Anaef mice exhibit anti-nuclear autoantibodies and gradually accumulate a CD44hi Helios+ PD-1+ CD4+ T cell population that is dependent on B cells. Despite reduced Rasgrp1-Ras-ERK activation in vitro, thymocyte selection in Rasgrp1Anaef is mostly normal in vivo, although CD44 is overexpressed on naïve thymocytes and T cells in a T-cell-autonomous manner. We identify CD44 expression as a sensitive reporter of tonic mTOR-S6 kinase signaling through a novel mouse strain, chino, with a reduction-of-function mutation in Mtor. Elevated tonic mTOR-S6 signaling occurs in Rasgrp1Anaef naïve CD4+ T cells. CD44 expression, CD4+ T cell subset ratios and serum autoantibodies all returned to normal in Rasgrp1AnaefMtorchino double-mutant mice, demonstrating that increased mTOR activity is essential for the Rasgrp1Anaef T cell dysregulation

Rasgrp1 mutation increases naïve T-cell CD44 expression and drives mTOR-dependent accumulation of Helios⁺ T cells and autoantibodies

Missense variants are a major source of human genetic variation. Here we analyze a new mouse missense variant, Rasgrp1ᴬⁿᵃᵉᶠ, with an ENU-mutated EF hand in the Rasgrp1 Ras guanine nucleotide exchange factor. Rasgrp1ᴬⁿᵃᵉᶠ mice exhibit anti-nuclear autoantibodies and gradually accumulate a CD44hi Helios⁺ PD-1⁺ CD4⁺ T cell population that is dependent on B cells. Despite reduced Rasgrp1-Ras-ERK activation in vitro, thymocyte selection in Rasgrp1ᴬⁿᵃᵉᶠ is mostly normal in vivo, although CD44 is overexpressed on naïve thymocytes and T cells in a T-cell-autonomous manner. We identify CD44 expression as a sensitive reporter of tonic mTOR-S6 kinase signaling through a novel mouse strain, chino, with a reduction-of-function mutation in Mtor. Elevated tonic mTOR-S6 signaling occurs in Rasgrp1ᴬⁿᵃᵉᶠ naïve CD4⁺ T cells. CD44 expression, CD4⁺ T cell subset ratios and serum autoantibodies all returned to normal in Rasgrp1ᴬⁿᵃᵉᶠMtorᶜʰⁱⁿᵒ double-mutant mice, demonstrating that increased mTOR activity is essential for the Rasgrp1ᴬⁿᵃᵉᶠ T cell dysregulation

DOCK8 deficiency impairs CD8 T cell survival and function in humans and mice

As shown by analysis of mice and humans bearing DOCK8-inactivating mutations, DOCK8 plays a cell-autonomous role in survival of naive CD8 T cells, LFA-1 polarization toward the immune synapse, and CD8 T cell memory and recall responses following viral infection

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy