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Sample records for absent dynein arms

  1. Substructure of the outer dynein arm

    PubMed Central

    1982-01-01

    The substructure of the outer dynein arm has been analyzed in quick- frozen deep-etch replicas of Tetrahymena and Chlamydomonas axonemes. Each arm is found to be composed of five morphologically discrete components: an elliptical head; two spherical feet; a slender stalk; and an interdynein linker. The feet make contact with the A microtubule of each doublet; the stalk contacts the B microtubule; the head lies between the feet and stalk; and the linker associates each arm with its neighbor. The spatial relationships between these five components are found to be distinctly different in rigor (ATP-depleted) versus relaxed (ATP- or vanadate plus ATP-treated) axonemes, and the stalk appears to alter its affinity for the B microtubule in the relaxed state. Images of living cilia attached to Tetrahymena cells show that the relaxed configuration is adopted in vivo. We relate our observations to morphological and experimental studies reported by others and propose several models that suggest how this newly described dynein morphology may relate to dynein function. PMID:6218174

  2. LRRC6 Mutation Causes Primary Ciliary Dyskinesia with Dynein Arm Defects

    PubMed Central

    Horani, Amjad; Ferkol, Thomas W.; Shoseyov, David; Wasserman, Mollie G.; Oren, Yifat S.; Kerem, Batsheva; Amirav, Israel; Cohen-Cymberknoh, Malena; Dutcher, Susan K.; Brody, Steven L.; Elpeleg, Orly; Kerem, Eitan

    2013-01-01

    Despite recent progress in defining the ciliome, the genetic basis for many cases of primary ciliary dyskinesia (PCD) remains elusive. We evaluated five children from two unrelated, consanguineous Palestinian families who had PCD with typical clinical features, reduced nasal nitric oxide concentrations, and absent dynein arms. Linkage analyses revealed a single common homozygous region on chromosome 8 and one candidate was conserved in organisms with motile cilia. Sequencing revealed a single novel mutation in LRRC6 (Leucine-rich repeat containing protein 6) that fit the model of autosomal recessive genetic transmission, leading to a change of a highly conserved amino acid from aspartic acid to histidine (Asp146His). LRRC6 was localized to the cytoplasm and was up-regulated during ciliogenesis in human airway epithelial cells in a Foxj1-dependent fashion. Nasal epithelial cells isolated from affected individuals and shRNA-mediated silencing in human airway epithelial cells, showed reduced LRRC6 expression, absent dynein arms, and slowed cilia beat frequency. Dynein arm proteins were either absent or mislocalized to the cytoplasm in airway epithelial cells from a primary ciliary dyskinesia subject. These findings suggest that LRRC6 plays a role in dynein arm assembly or trafficking and when mutated leads to primary ciliary dyskinesia with laterality defects. PMID:23527195

  3. Functional Architecture of the Outer Arm Dynein Conformational Switch*

    PubMed Central

    King, Stephen M.; Patel-King, Ramila S.

    2012-01-01

    Dynein light chain 1 (LC1/DNAL1) is one of the most highly conserved components of ciliary axonemal outer arm dyneins, and it associates with both a heavy chain motor unit and tubulin located within the A-tubule of the axonemal outer doublet microtubules. In a variety of model systems, lack of LC1 or expression of mutant forms leads to profound defects in ciliary motility, including the failure of the hydrodynamic coupling needed for ciliary metachronal synchrony, random stalling during the power/recovery stroke transition, an aberrant response to imposed viscous load, and in some cases partial failure of motor assembly. These phenotypes have led to the proposal that LC1 acts as part of a mechanical switch to control motor function in response to alterations in axonemal curvature. Here we have used NMR chemical shift mapping to define the regions perturbed by a series of mutations in the C-terminal domain that yield a range of phenotypic effects on motility. In addition, we have identified the subdomain of LC1 involved in binding microtubules and characterized the consequences of an Asn → Ser alteration within the terminal leucine-rich repeat that in humans causes primary ciliary dyskinesia. Together, these data define a series of functional subdomains within LC1 and allow us to propose a structural model for the organization of the dynein heavy chain-LC1-microtubule ternary complex that is required for the coordinated activity of dynein motors in cilia. PMID:22157010

  4. Molecular architecture of inner dynein arms in situ in Chlamydomonas reinhardtii flagella

    PubMed Central

    Bui, Khanh Huy; Sakakibara, Hitoshi; Movassagh, Tandis; Oiwa, Kazuhiro; Ishikawa, Takashi

    2008-01-01

    The inner dynein arm regulates axonemal bending motion in eukaryotes. We used cryo-electron tomography to reconstruct the three-dimensional structure of inner dynein arms from Chlamydomonas reinhardtii. All the eight different heavy chains were identified in one 96-nm periodic repeat, as expected from previous biochemical studies. Based on mutants, we identified the positions of the AAA rings and the N-terminal tails of all the eight heavy chains. The dynein f dimer is located close to the surface of the A-microtubule, whereas the other six heavy chain rings are roughly colinear at a larger distance to form three dyads. Each dyad consists of two heavy chains and has a corresponding radial spoke or a similar feature. In each of the six heavy chains (dynein a, b, c, d, e, and g), the N-terminal tail extends from the distal side of the ring. To interact with the B-microtubule through stalks, the inner-arm dyneins must have either different handedness or, more probably, the opposite orientation of the AAA rings compared with the outer-arm dyneins. PMID:19029338

  5. Tubulin Glutamylation Regulates Ciliary Motility by Altering Inner Dynein Arm Activity

    PubMed Central

    Suryavanshi, Swati; Eddé, Bernard; Fox, Laura A.; Guerrero, Stella; Hard, Robert; Hennessey, Todd; Kabi, Amrita; Malison, David; Pennock, David; Sale, Winfield S.; Wloga, Dorota; Gaertig, Jacek

    2010-01-01

    SUMMMARY How microtubule-associated motor proteins are regulated is not well understood. A potential mechanism for spatial regulation of motor proteins is provided by post-translational modifications of tubulin subunits that form patterns on microtubules. Glutamylation is a conserved tubulin modification [1] that is enriched in axonemes. The enzymes responsible for this PTM, glutamic acid ligases (E-ligases), belong to a family of proteins with a tubulin tyrosine ligase (TTL) homology domain (TTL-like or TTLL proteins) [2]. We show that in cilia of Tetrahymena, TTLL6 E-ligases generate glutamylation mainly on the B-tubule of outer doublet microtubules, the site of force production by ciliary dynein. Deletion of two TTLL6 paralogs caused severe deficiency in ciliary motility associated with abnormal waveform and reduced beat frequency. In isolated axonemes with a normal dynein arm composition, TTLL6 deficiency did not affect the rate of ATP-induced doublet microtubule sliding. Unexpectedly, the same TTLL6 deficiency increased the velocity of microtubule sliding in axonemes that also lack outer dynein arms, in which forces are generated by inner dynein arms. We conclude that tubulin glutamylation on the B-tubule inhibits the net force imposed on sliding doublet microtubules by inner dynein arms. PMID:20189389

  6. Three Members of the LC8/DYNLL Family Are Required for Outer Arm Dynein Motor Function

    PubMed Central

    Tanner, Christopher A.; Rompolas, Panteleimon; Patel-King, Ramila S.; Gorbatyuk, Oksana; Wakabayashi, Ken-ichi; Pazour, Gregory J.

    2008-01-01

    The highly conserved LC8/DYNLL family proteins were originally identified in axonemal dyneins and subsequently found to function in multiple enzyme systems. Genomic analysis uncovered a third member (LC10) of this protein class in Chlamydomonas. The LC10 protein is extracted from flagellar axonemes with 0.6 M NaCl and cofractionates with the outer dynein arm in sucrose density gradients. Furthermore, LC10 is specifically missing only from axonemes of those strains that fail to assemble outer dynein arms. Previously, the oda12-1 insertional allele was shown to lack the Tctex2-related dynein light chain LC2. The LC10 gene is located ∼2 kb from that of LC2 and is also completely missing from this mutant but not from oda12-2, which lacks only the 3′ end of the LC2 gene. Although oda12-1 cells assemble outer arms that lack only LC2 and LC10, this strain exhibits a flagellar beat frequency that is consistently less than that observed for strains that fail to assemble the entire outer arm and docking complex (e.g., oda1). These results support a key regulatory role for the intermediate chain/light chain complex that is an integral and highly conserved feature of all oligomeric dynein motors. PMID:18579685

  7. CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms

    PubMed Central

    Panizzi, Jennifer R.; Becker-Heck, Anita; Castleman, Victoria H.; Al-Mutairi, Dalal; Liu, Yan; Loges, Niki T.; Pathak, Narendra; Austin-Tse, Christina; Sheridan, Eamonn; Schmidts, Miriam; Olbrich, Heike; Werner, Claudius; Häffner, Karsten; Hellman, Nathan; Chodhari, Rahul; Gupta, Amar; Kramer-Zucker, Albrecht; Olale, Felix; Burdine, Rebecca D.; Schier, Alexander F.; O’Callaghan, Christopher; Chung, Eddie MK; Reinhardt, Richard; Mitchison, Hannah M.; King, Stephen M.; Omran, Heymut; Drummond, Iain A.

    2012-01-01

    Cilia are essential for fertilization, respiratory clearance, cerebrospinal fluid circulation, and to establish laterality1. Cilia motility defects cause Primary Ciliary Dyskinesia (PCD, MIM 242650), a disorder affecting 1:15-30,000 births. Cilia motility requires the assembly of multisubunit dynein arms that drive cilia bending2. Despite progress in understanding the genetic basis of PCD, mutations remain to be identified for several PCD linked loci3. Here we show that the zebrafish cilia paralysis mutant schmalhanstn222 (smh) mutant encodes the coiled-coil domain containing 103 protein (Ccdc103), a foxj1a regulated gene. Screening 146 unrelated PCD families identified patients in six families with reduced outer dynein arms, carrying mutations in CCDC103. Dynein arm assembly in smh mutant zebrafish was rescued by wild-type but not mutant human CCDC103. Chlamydomonas Ccdc103 functions as a tightly bound, axoneme-associated protein. The results identify Ccdc103 as a novel dynein arm attachment factor that when mutated causes Primary Ciliary Dyskinesia. PMID:22581229

  8. An Outer Arm Dynein Conformational Switch Is Required for Metachronal Synchrony of Motile Cilia in Planaria

    PubMed Central

    Rompolas, Panteleimon; Patel-King, Ramila S.

    2010-01-01

    Motile cilia mediate the flow of mucus and other fluids across the surface of specialized epithelia in metazoans. Efficient clearance of peri-ciliary fluids depends on the precise coordination of ciliary beating to produce metachronal waves. The role of individual dynein motors and the mechanical feedback mechanisms required for this process are not well understood. Here we used the ciliated epithelium of the planarian Schmidtea mediterranea to dissect the role of outer arm dynein motors in the metachronal synchrony of motile cilia. We demonstrate that animals that completely lack outer dynein arms display a significant decline in beat frequency and an inability of cilia to coordinate their oscillations and form metachronal waves. Furthermore, lack of a key mechanosensitive regulatory component (LC1) yields a similar phenotype even though outer arms still assemble in the axoneme. The lack of metachrony was not due simply to a decrease in ciliary beat frequency, as reducing this parameter by altering medium viscosity did not affect ciliary coordination. In addition, we did not observe a significant temporal variability in the beat cycle of impaired cilia. We propose that this conformational switch provides a mechanical feedback system within outer arm dynein that is necessary to entrain metachronal synchrony. PMID:20844081

  9. ZMYND10 stabilizes intermediate chain proteins in the cytoplasmic pre-assembly of dynein arms.

    PubMed

    Cho, Kyeong Jee; Noh, Shin Hye; Han, Soo Min; Choi, Won-Il; Kim, Hye-Youn; Yu, Seyoung; Lee, Joon Suk; Rim, John Hoon; Lee, Min Goo; Hildebrandt, Friedhelm; Gee, Heon Yung

    2018-03-01

    Zinc finger MYND-type-containing 10 (ZMYND10), a cytoplasmic protein expressed in ciliated cells, causes primary ciliary dyskinesia (PCD) when mutated; however, its function is poorly understood. Therefore, in this study, we examined the roles of ZMYND10 using Zmynd10-/-mice exhibiting typical PCD phenotypes, including hydrocephalus and laterality defects. In these mutants, morphology, the number of motile cilia, and the 9+2 axoneme structure were normal; however, inner and outer dynein arms (IDA and ODA, respectively) were absent. ZMYND10 interacted with ODA components and proteins, including LRRC6, DYX1C1, and C21ORF59, implicated in the cytoplasmic pre-assembly of DAs, whose levels were significantly reduced in Zmynd10-/-mice. LRRC6 and DNAI1 were more stable when co-expressed with ZYMND10 than when expressed alone. DNAI2, which did not interact with ZMYND10, was not stabilized by co-expression with ZMYND10 alone, but was stabilized by co-expression with DNAI1 and ZMYND10, suggesting that ZMYND10 stabilized DNAI1, which subsequently stabilized DNAI2. Together, these results demonstrated that ZMYND10 regulated the early stage of DA cytoplasmic pre-assembly by stabilizing DNAI1.

  10. The Mr 140,000 Intermediate Chain of Chlamydomonas Flagellar Inner Arm Dynein Is a WD-Repeat Protein Implicated in Dynein Arm Anchoring

    PubMed Central

    Yang, Pinfen; Sale, Winfield S.

    1998-01-01

    Previous structural and biochemical studies have revealed that the inner arm dynein I1 is targeted and anchored to a unique site located proximal to the first radial spoke in each 96-nm axoneme repeat on flagellar doublet microtubules. To determine whether intermediate chains mediate the positioning and docking of dynein complexes, we cloned and characterized the 140-kDa intermediate chain (IC140) of the I1 complex. Sequence and secondary structural analysis, with particular emphasis on β-sheet organization, predicted that IC140 contains seven WD repeats. Reexamination of other members of the dynein intermediate chain family of WD proteins indicated that these polypeptides also bear seven WD/β-sheet repeats arranged in the same pattern along each intermediate chain protein. A polyclonal antibody was raised against a 53-kDa fusion protein derived from the C-terminal third of IC140. The antibody is highly specific for IC140 and does not bind to other dynein intermediate chains or proteins in Chlamydomonas flagella. Immunofluorescent microscopy of Chlamydomonas cells confirmed that IC140 is distributed along the length of both flagellar axonemes. In vitro reconstitution experiments demonstrated that the 53-kDa C-terminal fusion protein binds specifically to axonemes lacking the I1 complex. Chemical cross-linking indicated that IC140 is closely associated with a second intermediate chain in the I1 complex. These data suggest that IC140 contains domains responsible for the assembly and docking of the I1 complex to the doublet microtubule cargo. PMID:9843573

  11. Chlamydomonas DYX1C1/PF23 is essential for axonemal assembly and proper morphology of inner dynein arms

    PubMed Central

    Yamamoto, Ryosuke; Alford, Lea M.; Ide, Takahiro; Owa, Mikito; Hwang, Juyeon; Inaba, Kazuo; James, Noliyanda; Ishikawa, Takashi

    2017-01-01

    Cytoplasmic assembly of ciliary dyneins, a process known as preassembly, requires numerous non-dynein proteins, but the identities and functions of these proteins are not fully elucidated. Here, we show that the classical Chlamydomonas motility mutant pf23 is defective in the Chlamydomonas homolog of DYX1C1. The pf23 mutant has a 494 bp deletion in the DYX1C1 gene and expresses a shorter DYX1C1 protein in the cytoplasm. Structural analyses, using cryo-ET, reveal that pf23 axonemes lack most of the inner dynein arms. Spectral counting confirms that DYX1C1 is essential for the assembly of the majority of ciliary inner dynein arms (IDA) as well as a fraction of the outer dynein arms (ODA). A C-terminal truncation of DYX1C1 shows a reduction in a subset of these ciliary IDAs. Sucrose gradients of cytoplasmic extracts show that preassembled ciliary dyneins are reduced compared to wild-type, which suggests an important role in dynein complex stability. The role of PF23/DYX1C1 remains unknown, but we suggest that DYX1C1 could provide a scaffold for macromolecular assembly. PMID:28892495

  12. An outer arm dynein light chain acts in a conformational switch for flagellar motility

    PubMed Central

    Patel-King, Ramila S.

    2009-01-01

    A system distinct from the central pair–radial spoke complex was proposed to control outer arm dynein function in response to alterations in the mechanical state of the flagellum. In this study, we examine the role of a Chlamydomonas reinhardtii outer arm dynein light chain that associates with the motor domain of the γ heavy chain (HC). We demonstrate that expression of mutant forms of LC1 yield dominant-negative effects on swimming velocity, as the flagella continually beat out of phase and stall near or at the power/recovery stroke switchpoint. Furthermore, we observed that LC1 interacts directly with tubulin in a nucleotide-independent manner and tethers this motor unit to the A-tubule of the outer doublet microtubules within the axoneme. Therefore, this dynein HC is attached to the same microtubule by two sites: via both the N-terminal region and the motor domain. We propose that this γ HC–LC1–microtubule ternary complex functions as a conformational switch to control outer arm activity. PMID:19620633

  13. Chlamydomonas Outer Arm Dynein Alters Conformation in Response to Ca2+

    PubMed Central

    Sakato, Miho; Sakakibara, Hitoshi

    2007-01-01

    We have previously shown that Ca2+ directly activates ATP-sensitive microtubule binding by a Chlamydomonas outer arm dynein subparticle containing the β and γ heavy chains (HCs). The γ HC–associated LC4 light chain is a member of the calmodulin family and binds 1-2 Ca2+ with KCa = 3 × 10−5 M in vitro, suggesting it may act as a Ca2+ sensor for outer arm dynein. Here we investigate interactions between the LC4 light chain and γ HC. Two IQ consensus motifs for binding calmodulin-like proteins are located within the stem domain of the γ heavy chain. In vitro experiments indicate that LC4 undergoes a Ca2+-dependent interaction with the IQ motif domain while remaining tethered to the HC. LC4 also moves into close proximity of the intermediate chain IC1 in the presence of Ca2+. The sedimentation profile of the γ HC subunit changed subtly upon Ca2+ addition, suggesting that the entire complex had become more compact, and electron microscopy of the isolated γ subunit revealed a distinct alteration in conformation of the N-terminal stem in response to Ca2+ addition. We propose that Ca2+-dependent conformational change of LC4 has a direct effect on the stem domain of the γ HC, which eventually leads to alterations in mechanochemical interactions between microtubules and the motor domain(s) of the outer dynein arm. PMID:17634291

  14. Association of Lis1 with outer arm dynein is modulated in response to alterations in flagellar motility

    PubMed Central

    Rompolas, Panteleimon; Patel-King, Ramila S.; King, Stephen M.

    2012-01-01

    The cytoplasmic dynein regulatory factor Lis1, which induces a persistent tight binding to microtubules and allows for transport of cargoes under high-load conditions, is also present in motile cilia/flagella. We observed that Lis1 levels in flagella of Chlamydomonas strains that exhibit defective motility due to mutation of various axonemal substructures were greatly enhanced compared with wild type; this increase was absolutely dependent on the presence within the flagellum of the outer arm dynein α heavy chain/light chain 5 thioredoxin unit. To assess whether cells might interpret defective motility as a “high-load environment,” we reduced the flagellar beat frequency of wild-type cells through enhanced viscous load and by reductive stress; both treatments resulted in increased levels of flagellar Lis1, which altered the intrinsic beat frequency of the trans flagellum. Differential extraction of Lis1 from wild-type and mutant axonemes suggests that the affinity of outer arm dynein for Lis1 is directly modulated. In cytoplasm, Lis1 localized to two punctate structures, one of which was located near the base of the flagella. These data reveal that the cell actively monitors motility and dynamically modulates flagellar levels of the dynein regulatory factor Lis1 in response to imposed alterations in beat parameters. PMID:22855525

  15. Distinct roles of 1α and 1β heavy chains of the inner arm dynein I1 of Chlamydomonas flagella

    PubMed Central

    Toba, Shiori; Fox, Laura A.; Sakakibara, Hitoshi; Porter, Mary E.; Oiwa, Kazuhiro; Sale, Winfield S.

    2011-01-01

    The Chlamydomonas I1 dynein is a two-headed inner dynein arm important for the regulation of flagellar bending. Here we took advantage of mutant strains lacking either the 1α or 1β motor domain to distinguish the functional role of each motor domain. Single- particle electronic microscopic analysis confirmed that both the I1α and I1β complexes are single headed with similar ringlike, motor domain structures. Despite similarity in structure, however, the I1β complex has severalfold higher ATPase activity and microtubule gliding motility compared to the I1α complex. Moreover, in vivo measurement of microtubule sliding in axonemes revealed that the loss of the 1β motor results in a more severe impairment in motility and failure in regulation of microtubule sliding by the I1 dynein phosphoregulatory mechanism. The data indicate that each I1 motor domain is distinct in function: The I1β motor domain is an effective motor required for wild-type microtubule sliding, whereas the I1α motor domain may be responsible for local restraint of microtubule sliding. PMID:21148301

  16. The N-terminus of IFT46 mediates intraflagellar transport of outer arm dynein and its cargo-adaptor ODA16

    PubMed Central

    Hou, Yuqing; Witman, George B.

    2017-01-01

    Cilia are assembled via intraflagellar transport (IFT). The IFT machinery is composed of motors and multisubunit particles, termed IFT-A and IFT-B, that carry cargo into the cilium. Knowledge of how the IFT subunits interact with their cargo is of critical importance for understanding how the unique ciliary domain is established. We previously reported a Chlamydomonas mutant, ift46-1, that fails to express the IFT-B protein IFT46, has greatly reduced levels of other IFT-B proteins, and assembles only very short flagella. A spontaneous suppression of ift46-1 restored IFT-B levels and enabled growth of longer flagella, but the flagella lacked outer dynein arms. Here we show that the suppression is due to insertion of the transposon MRC1 into the ift46-1 allele, causing the expression of a fusion protein including the IFT46 C-terminal 240 amino acids. The IFT46 C-terminus can assemble into and stabilize IFT-B but does not support transport of outer arm dynein into flagella. ODA16, a cargo adaptor specific for outer arm dynein, also fails to be imported into the flagella in the absence of the IFT46 N-terminus. We conclude that the IFT46 N-terminus, ODA16, and outer arm dynein interact for IFT of the latter. PMID:28701346

  17. Mice Deficient in the Axonemal Protein Tektin-t Exhibit Male Infertility and Immotile-Cilium Syndrome Due to Impaired Inner Arm Dynein Function

    PubMed Central

    Tanaka, Hiromitsu; Iguchi, Naoko; Toyama, Yoshiro; Kitamura, Kouichi; Takahashi, Tohru; Kaseda, Kazuhiro; Maekawa, Mamiko; Nishimune, Yoshitake

    2004-01-01

    The haploid germ cell-specific Tektin-t protein is a member of the Tektin family of proteins that form filaments in flagellar, ciliary, and axonemal microtubules. To investigate the physiological role of Tektin-t, we generated mice with a mutation in the tektin-t gene. The homozygous mutant males were infertile, while the females were fully fertile. Sperm morphology and function were abnormal, with frequent bending of the sperm flagella and marked defects in motility. In vitro fertilization assays showed that the defective spermatozoa were able to fertilize eggs. Electron microscopic examination showed that the dynein inner arm structure was disrupted in the sperm flagella of tektin-t-deficient mice. Furthermore, homozygous mutant mice had functionally defective tracheal cilia, as evidenced by altered dynein arm morphology. These results indicate that Tektin-t participates in dynein inner arm formation or attachment and that the loss of Tektin-t results in impaired motility of both flagella and cilia. Therefore, the tektin-t gene is one of the causal genes for immotile-cilium syndrome/primary ciliary dyskinesia. PMID:15340058

  18. Three outer arm dynein heavy chains of Chlamydomonas reinhardtii operate in a coordinated fashion both in vitro and in vivo.

    PubMed

    Takazaki, Hiroko; Liu, Zhongmei; Jin, Mingyue; Kamiya, Ritsu; Yasunaga, Takuo

    2010-07-01

    Outer arm dynein (OAD) in cilia and flagella contains two to three nonidentical heavy chains (HCs) that possess motor activity. In Chlamydomonas, flagellar OAD contains three HCs, alpha-, beta-, and gamma-HCs, each appearing to have a distinct role. To determine the precise molecular mechanism of their function, cross-sectional electron micrographs of wild-type and single HC-disruption mutants were compared and statistically analyzed. While the alpha-HC mutant displayed an OAD of lower density, which was attributed to a lack of alpha-HC, the OAD of beta- and gamma-HC mutants not only lacked the corresponding HC, but was also significantly affected in its structure, particularly with respect to the localization of alpha-HC. The lack of beta-HC induced mislocalization of alpha-HC, while a disruption of the gamma-HC gene resulted in the synchronized movement of alpha-HC and beta-HC in the manners for stacking. Interestingly, using cryo-electron microscopy, purified OADs were typically observed consisting of two stacked heads and an independent single head, which presumably corresponded to gamma-HC. This conformation is different from previous reports in which the three HCs displayed a stacked form in flagella observed by cryo-electron tomography and a bouquet structure on mica in deep-etch replica images. These results suggest that gamma-HC supports the tight stacking arrangement of inter or intra alpha-/beta-HC to facilitate the proper functioning of OAD. 2010 Wiley-Liss, Inc.

  19. Mutations in ZMYND10, a Gene Essential for Proper Axonemal Assembly of Inner and Outer Dynein Arms in Humans and Flies, Cause Primary Ciliary Dyskinesia

    PubMed Central

    Moore, Daniel J.; Onoufriadis, Alexandros; Shoemark, Amelia; Simpson, Michael A.; zur Lage, Petra I.; de Castro, Sandra C.; Bartoloni, Lucia; Gallone, Giuseppe; Petridi, Stavroula; Woollard, Wesley J.; Antony, Dinu; Schmidts, Miriam; Didonna, Teresa; Makrythanasis, Periklis; Bevillard, Jeremy; Mongan, Nigel P.; Djakow, Jana; Pals, Gerard; Lucas, Jane S.; Marthin, June K.; Nielsen, Kim G.; Santoni, Federico; Guipponi, Michel; Hogg, Claire; Antonarakis, Stylianos E.; Emes, Richard D.; Chung, Eddie M.K.; Greene, Nicholas D.E.; Blouin, Jean-Louis; Jarman, Andrew P.; Mitchison, Hannah M.

    2013-01-01

    Primary ciliary dyskinesia (PCD) is a ciliopathy characterized by airway disease, infertility, and laterality defects, often caused by dual loss of the inner dynein arms (IDAs) and outer dynein arms (ODAs), which power cilia and flagella beating. Using whole-exome and candidate-gene Sanger resequencing in PCD-affected families afflicted with combined IDA and ODA defects, we found that 6/38 (16%) carried biallelic mutations in the conserved zinc-finger gene BLU (ZMYND10). ZMYND10 mutations conferred dynein-arm loss seen at the ultrastructural and immunofluorescence level and complete cilia immotility, except in hypomorphic p.Val16Gly (c.47T>G) homozygote individuals, whose cilia retained a stiff and slowed beat. In mice, Zmynd10 mRNA is restricted to regions containing motile cilia. In a Drosophila model of PCD, Zmynd10 is exclusively expressed in cells with motile cilia: chordotonal sensory neurons and sperm. In these cells, P-element-mediated gene silencing caused IDA and ODA defects, proprioception deficits, and sterility due to immotile sperm. Drosophila Zmynd10 with an equivalent c.47T>G (p.Val16Gly) missense change rescued mutant male sterility less than the wild-type did. Tagged Drosophila ZMYND10 is localized primarily to the cytoplasm, and human ZMYND10 interacts with LRRC6, another cytoplasmically localized protein altered in PCD. Using a fly model of PCD, we conclude that ZMYND10 is a cytoplasmic protein required for IDA and ODA assembly and that its variants cause ciliary dysmotility and PCD with laterality defects. PMID:23891471

  20. The Chlamydomonas Dhc1 gene encodes a dynein heavy chain subunit required for assembly of the I1 inner arm complex.

    PubMed Central

    Myster, S H; Knott, J A; O'Toole, E; Porter, M E

    1997-01-01

    Multiple members of the dynein heavy chain (Dhc) gene family have been recovered in several organisms, but the relationships between these sequences and the Dhc isoforms that they encode are largely unknown. To identify Dhc loci and determine the specific functions of the individual Dhc isoforms, we have screened a collection of motility mutants generated by insertional mutagenesis in Chlamydomonas. In this report, we characterize one strain, pf9-3, in which the insertion event was accompanied by a deletion of approximately 13 kb of genomic DNA within the transcription unit of the Dhc1 gene. Northern blot analysis confirms that pf9-3 is a null mutation. Biochemical and structural studies of isolated axonemes demonstrate that the pf9-3 mutant fails to assemble the I1 inner arm complex, a two-headed dynein isoform composed of two Dhcs (1 alpha and 1 beta) and three intermediate chains. To determine if the Dhc1 gene product corresponds to one of the Dhcs of the I1 complex, antibodies were generated against a Dhc1-specific peptide sequence. Immunoblot analysis reveals that the Dhc1 gene encodes the 1 alpha Dhc subunit. These studies thus, identify the first inner arm Dhc locus to be described in any organism and further demonstrate that the 1 alpha Dhc subunit plays an essential role in the assembly of the I1 inner arm complex. Images PMID:9247642

  1. Can widespread hypersensitivity in carpal tunnel syndrome be substantiated if neck and arm pain are absent?

    PubMed

    Schmid, A B; Soon, B T C; Wasner, G; Coppieters, M W

    2012-02-01

    Recent studies demonstrated that patients with carpal tunnel syndrome (CTS) have signs of thermal and mechanical hyperalgesia in extra-median territories suggesting an involvement of central pain mechanisms. As previous studies included patients with shoulder/arm symptoms or neck pain, a potential influence of these coexisting disorders cannot be excluded. This study therefore evaluated whether widespread sensory changes (hypoesthesia or hyperalgesia) are present in patients with unilateral CTS in the absence of coexisting disorders. Twenty-six patients with unilateral CTS with symptoms localised to their hand and 26 healthy controls participated in the study. A comprehensive quantitative sensory testing (QST) protocol including thermal and mechanical detection and pain thresholds was performed over the hands (median, ulnar and radial innervation area), lateral elbows, neck and tibialis anterior muscle. Patients with CTS demonstrated thermal and mechanical hypoesthesia in the hand but not at distant sites. Thermal or mechanical hyperalgesia was not identified at any location with traditional QST threshold testing. However, patients with CTS rated the pain during thermal pain testing significantly higher than healthy participants. This was especially apparent for heat pain ratings which were elevated not only in the affected hand but also in the neck and tibialis anterior muscle. In conclusion, CTS alone in the absence of coexisting neck and arm pain does not account for sensory changes outside the affected hand as determined by traditional QST threshold testing. Elevated pain ratings may however be an early indication of central pain mechanisms. © 2011 European Federation of International Association for the Study of Pain Chapters.

  2. TTC25 Deficiency Results in Defects of the Outer Dynein Arm Docking Machinery and Primary Ciliary Dyskinesia with Left-Right Body Asymmetry Randomization.

    PubMed

    Wallmeier, Julia; Shiratori, Hidetaka; Dougherty, Gerard W; Edelbusch, Christine; Hjeij, Rim; Loges, Niki T; Menchen, Tabea; Olbrich, Heike; Pennekamp, Petra; Raidt, Johanna; Werner, Claudius; Minegishi, Katsura; Shinohara, Kyosuke; Asai, Yasuko; Takaoka, Katsuyoshi; Lee, Chanjae; Griese, Matthias; Memari, Yasin; Durbin, Richard; Kolb-Kokocinski, Anja; Sauer, Sascha; Wallingford, John B; Hamada, Hiroshi; Omran, Heymut

    2016-08-04

    Multiprotein complexes referred to as outer dynein arms (ODAs) develop the main mechanical force to generate the ciliary and flagellar beat. ODA defects are the most common cause of primary ciliary dyskinesia (PCD), a congenital disorder of ciliary beating, characterized by recurrent infections of the upper and lower airways, as well as by progressive lung failure and randomization of left-right body asymmetry. Using a whole-exome sequencing approach, we identified recessive loss-of-function mutations within TTC25 in three individuals from two unrelated families affected by PCD. Mice generated by CRISPR/Cas9 technology and carrying a deletion of exons 2 and 3 in Ttc25 presented with laterality defects. Consistently, we observed immotile nodal cilia and missing leftward flow via particle image velocimetry. Furthermore, transmission electron microscopy (TEM) analysis in TTC25-deficient mice revealed an absence of ODAs. Consistent with our findings in mice, we were able to show loss of the ciliary ODAs in humans via TEM and immunofluorescence (IF) analyses. Additionally, IF analyses revealed an absence of the ODA docking complex (ODA-DC), along with its known components CCDC114, CCDC151, and ARMC4. Co-immunoprecipitation revealed interaction between the ODA-DC component CCDC114 and TTC25. Thus, here we report TTC25 as a new member of the ODA-DC machinery in humans and mice. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  3. Primary Ciliary Dyskinesia Caused by Homozygous Mutation in DNAL1, Encoding Dynein Light Chain 1

    PubMed Central

    Mazor, Masha; Alkrinawi, Soliman; Chalifa-Caspi, Vered; Manor, Esther; Sheffield, Val C.; Aviram, Micha; Parvari, Ruti

    2011-01-01

    In primary ciliary dyskinesia (PCD), genetic defects affecting motility of cilia and flagella cause chronic destructive airway disease, randomization of left-right body asymmetry, and, frequently, male infertility. The most frequent defects involve outer and inner dynein arms (ODAs and IDAs) that are large multiprotein complexes responsible for cilia-beat generation and regulation, respectively. Although it has long been suspected that mutations in DNAL1 encoding the ODA light chain1 might cause PCD such mutations were not found. We demonstrate here that a homozygous point mutation in this gene is associated with PCD with absent or markedly shortened ODA. The mutation (NM_031427.3: c.449A>G; p.Asn150Ser) changes the Asn at position150, which is critical for the proper tight turn between the β strand and the α helix of the leucine-rich repeat in the hydrophobic face that connects to the dynein heavy chain. The mutation reduces the stability of the axonemal dynein light chain 1 and damages its interactions with dynein heavy chain and with tubulin. This study adds another important component to understanding the types of mutations that cause PCD and provides clinical information regarding a specific mutation in a gene not yet known to be associated with PCD. PMID:21496787

  4. Primary ciliary dyskinesia caused by homozygous mutation in DNAL1, encoding dynein light chain 1.

    PubMed

    Mazor, Masha; Alkrinawi, Soliman; Chalifa-Caspi, Vered; Manor, Esther; Sheffield, Val C; Aviram, Micha; Parvari, Ruti

    2011-05-13

    In primary ciliary dyskinesia (PCD), genetic defects affecting motility of cilia and flagella cause chronic destructive airway disease, randomization of left-right body asymmetry, and, frequently, male infertility. The most frequent defects involve outer and inner dynein arms (ODAs and IDAs) that are large multiprotein complexes responsible for cilia-beat generation and regulation, respectively. Although it has long been suspected that mutations in DNAL1 encoding the ODA light chain1 might cause PCD such mutations were not found. We demonstrate here that a homozygous point mutation in this gene is associated with PCD with absent or markedly shortened ODA. The mutation (NM_031427.3: c.449A>G; p.Asn150Ser) changes the Asn at position150, which is critical for the proper tight turn between the β strand and the α helix of the leucine-rich repeat in the hydrophobic face that connects to the dynein heavy chain. The mutation reduces the stability of the axonemal dynein light chain 1 and damages its interactions with dynein heavy chain and with tubulin. This study adds another important component to understanding the types of mutations that cause PCD and provides clinical information regarding a specific mutation in a gene not yet known to be associated with PCD. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  5. Absent Apologies

    ERIC Educational Resources Information Center

    Drew, Paul; Hepburn, Alexa

    2016-01-01

    Absent apologies--apologies that were expected but are not forthcoming--are quite frequently identified and commented on, for instance in the media. In this article we discuss two kinds of evidence that apologies can be "noticeably" absent for participants in ordinary interactions. The first kind is the delays that can occur in the…

  6. Diverse Roles of Axonemal Dyneins in Drosophila Auditory Neuron Function and Mechanical Amplification in Hearing.

    PubMed

    Karak, Somdatta; Jacobs, Julie S; Kittelmann, Maike; Spalthoff, Christian; Katana, Radoslaw; Sivan-Loukianova, Elena; Schon, Michael A; Kernan, Maurice J; Eberl, Daniel F; Göpfert, Martin C

    2015-11-26

    Much like vertebrate hair cells, the chordotonal sensory neurons that mediate hearing in Drosophila are motile and amplify the mechanical input of the ear. Because the neurons bear mechanosensory primary cilia whose microtubule axonemes display dynein arms, we hypothesized that their motility is powered by dyneins. Here, we describe two axonemal dynein proteins that are required for Drosophila auditory neuron function, localize to their primary cilia, and differently contribute to mechanical amplification in hearing. Promoter fusions revealed that the two axonemal dynein genes Dmdnah3 (=CG17150) and Dmdnai2 (=CG6053) are expressed in chordotonal neurons, including the auditory ones in the fly's ear. Null alleles of both dyneins equally abolished electrical auditory neuron responses, yet whereas mutations in Dmdnah3 facilitated mechanical amplification, amplification was abolished by mutations in Dmdnai2. Epistasis analysis revealed that Dmdnah3 acts downstream of Nan-Iav channels in controlling the amplificatory gain. Dmdnai2, in addition to being required for amplification, was essential for outer dynein arms in auditory neuron cilia. This establishes diverse roles of axonemal dyneins in Drosophila auditory neuron function and links auditory neuron motility to primary cilia and axonemal dyneins. Mutant defects in sperm competition suggest that both dyneins also function in sperm motility.

  7. The Dynein Gene Family in Chlamydomonas Reinhardtii

    PubMed Central

    Porter, M. E.; Knott, J. A.; Myster, S. H.; Farlow, S. J.

    1996-01-01

    To correlate dynein heavy chain (Dhc) genes with flagellar mutations and gain insight into the function of specific dynein isoforms, we placed eight members of the Dhc gene family on the genetic map of Chlamydomonas. Using a PCR-based strategy, we cloned 11 Dhc genes from Chlamydomonas. Comparisons with other Dhc genes indicate that two clones correspond to genes encoding the alpha and beta heavy chains of the outer dynein arm. Alignment of the predicted amino acid sequences spanning the nucleotide binding site indicates that the remaining nine clones can be subdivided into three groups that are likely to include representatives of the inner-arm Dhc isoforms. Gene-specific probes reveal that each clone represents a single-copy gene that is expressed as a transcript of the appropriate size (>13 kb) sufficient to encode a high molecular weight Dhc polypeptide. The expression of all nine genes is upregulated in response to deflagellation, suggesting a role in axoneme assembly or motility. Restriction fragment length polymorphisms between divergent C. reinhardtii strains have been used to place each Dhc gene on the genetic map of Chlamydomonas. These studies lay the groundwork for correlating defects in different Dhc genes with specific flagellar mutations. PMID:8889521

  8. The MIA complex is a conserved and novel dynein regulator essential for normal ciliary motility

    PubMed Central

    Yamamoto, Ryosuke; Song, Kangkang; Yanagisawa, Haru-aki; Fox, Laura; Yagi, Toshiki; Wirschell, Maureen; Hirono, Masafumi; Kamiya, Ritsu; Nicastro, Daniela

    2013-01-01

    Axonemal dyneins must be precisely regulated and coordinated to produce ordered ciliary/flagellar motility, but how this is achieved is not understood. We analyzed two Chlamydomonas reinhardtii mutants, mia1 and mia2, which display slow swimming and low flagellar beat frequency. We found that the MIA1 and MIA2 genes encode conserved coiled-coil proteins, FAP100 and FAP73, respectively, which form the modifier of inner arms (MIA) complex in flagella. Cryo–electron tomography of mia mutant axonemes revealed that the MIA complex was located immediately distal to the intermediate/light chain complex of I1 dynein and structurally appeared to connect with the nexin–dynein regulatory complex. In axonemes from mutants that lack both the outer dynein arms and the MIA complex, I1 dynein failed to assemble, suggesting physical interactions between these three axonemal complexes and a role for the MIA complex in the stable assembly of I1 dynein. The MIA complex appears to regulate I1 dynein and possibly outer arm dyneins, which are both essential for normal motility. PMID:23569216

  9. Dynein-deficient flagella respond to increased viscosity with contrasting changes in power and recovery strokes.

    PubMed

    Wilson, Kate S; Gonzalez, Olivia; Dutcher, Susan K; Bayly, Philip V

    2015-09-01

    Changes in the flagellar waveform in response to increased viscosity were investigated in uniflagellate mutants of Chlamydomonas reinhardtii. We hypothesized that the waveforms of mutants lacking different dynein arms would change in different ways as viscosity was increased, and that these variations would illuminate the feedback pathways from force to dynein activity. Previous studies have investigated the effects of viscosity on cell body motion, propulsive force, and power in different mutants, but the effect on waveform has not yet been fully characterized. Beat frequency decreases with viscosity in wild-type uniflagellate (uni1) cells, and outer dynein arm deficient (oda2) mutants. In contrast, the inner dynein arm mutant ida1 (lacking I1/f) maintains beat frequency at high viscosity but alters its flagellar waveform more than either wild-type or oda2. The ida1 waveform is narrower than wild-type, primarily due to an abbreviated recovery stroke; this difference is amplified at high viscosity. The oda2 mutant in contrast, maintains a consistent waveform at high and low viscosity with a slightly longer power stroke than wild-type. Analysis of the delays and shear displacements between bends suggest that direct force feedback in the outer dynein arm system may initiate switching of dynein activity. In contrast, I1/f dynein appears to delay switching, most markedly at the initiation of the power stroke, possibly by controlling inter-doublet separation. © 2015 Wiley Periodicals, Inc.

  10. Dynein-deficient flagella respond to increased viscosity with contrasting changes in power and recovery strokes

    PubMed Central

    Wilson, Kate S.; Gonzalez, Olivia; Dutcher, Susan K.; Bayly, P.V.

    2015-01-01

    Changes in the flagellar waveform in response to increased viscosity were investigated in uniflagellate mutants of Chlamydomonas reinhardtii. We hypothesized that the waveforms of mutants lacking different dynein arms would change in different ways as viscosity was increased, and that these variations would illuminate the feedback pathways from force to dynein activity. Previous studies have investigated the effects of viscosity on cell body motion, propulsive force, and power in different mutants, but the effect on waveform has not yet been fully characterized. Beat frequency decreases with viscosity in wild-type uniflagellate (uni1) cells, and outer dynein arm deficient (oda2) mutants. In contrast, the inner dynein arm mutant ida1 (lacking I1/f) maintains beat frequency at high viscosity but alters its flagellar waveform more than either wild-type or oda2. The ida1 waveform is narrower than wild-type, primarily due to an abbreviated recovery stroke; this difference is amplified at high viscosity. The oda2 mutant in contrast, maintains a consistent waveform at high and low viscosity with a slightly longer power stroke than wild-type. Analysis of the delays and shear displacements between bends suggest that direct force feedback in the outer dynein arm system may initiate switching of dynein activity. In contrast, I1/f dynein appears to delay switching, most markedly at the initiation of the power stroke, possibly by controlling inter-doublet separation. PMID:26314933

  11. A solid-state control system for dynein-based ciliary/flagellar motility

    PubMed Central

    2013-01-01

    Ciliary and flagellar beating requires the coordinated action of multiple dyneins with different enzymatic and motor properties. In this issue, Yamamoto et al. (2013. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201211048) identify the MIA (modifier of inner arms) complex within the Chlamydomonas reinhardtii axoneme that physically links to a known regulatory structure and provides a signaling conduit from the radial spokes to an inner arm dynein essential for waveform determination. PMID:23569213

  12. Analyses of Dynein Heavy Chain Mutations Reveal Complex Interactions Between Dynein Motor Domains and Cellular Dynein Functions

    PubMed Central

    Sivagurunathan, Senthilkumar; Schnittker, Robert R.; Razafsky, David S.; Nandini, Swaran; Plamann, Michael D.; King, Stephen J.

    2012-01-01

    Cytoplasmic dynein transports cargoes for a variety of crucial cellular functions. However, since dynein is essential in most eukaryotic organisms, the in-depth study of the cellular function of dynein via genetic analysis of dynein mutations has not been practical. Here, we identify and characterize 34 different dynein heavy chain mutations using a genetic screen of the ascomycete fungus Neurospora crassa, in which dynein is nonessential. Interestingly, our studies show that these mutations segregate into five different classes based on the in vivo localization of the mutated dynein motors. Furthermore, we have determined that the different classes of dynein mutations alter vesicle trafficking, microtubule organization, and nuclear distribution in distinct ways and require dynactin to different extents. In addition, biochemical analyses of dynein from one mutant strain show a strong correlation between its in vitro biochemical properties and the aberrant intracellular function of that altered dynein. When the mutations were mapped to the published dynein crystal structure, we found that the three-dimensional structural locations of the heavy chain mutations were linked to particular classes of altered dynein functions observed in cells. Together, our data indicate that the five classes of dynein mutations represent the entrapment of dynein at five separate points in the dynein mechanochemical and transport cycles. We have developed N. crassa as a model system where we can dissect the complexities of dynein structure, function, and interaction with other proteins with genetic, biochemical, and cell biological studies. PMID:22649085

  13. Lipid Rafts Assemble Dynein Ensembles.

    PubMed

    Nirschl, Jeffrey J; Ghiretti, Amy E; Holzbaur, Erika L F

    2016-05-01

    New work by Rai et al. identifies a novel mechanism regulating phagosome transport in cells: the clustering of dynein motors into lipid microdomains, leading to enhanced unidirectional motility. Clustering may be especially important for dynein, a motor that works most efficiently in teams. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. IC97 Is a Novel Intermediate Chain of I1 Dynein That Interacts with Tubulin and Regulates Interdoublet Sliding

    PubMed Central

    Wirschell, Maureen; Yang, Chun; Yang, Pinfen; Fox, Laura; Yanagisawa, Haru-aki; Kamiya, Ritsu; Witman, George B.; Porter, Mary E.

    2009-01-01

    Our goal is to understand the assembly and regulation of flagellar dyneins, particularly the Chlamydomonas inner arm dynein called I1 dynein. Here, we focus on the uncharacterized I1-dynein IC IC97. The IC97 gene encodes a novel IC without notable structural domains. IC97 shares homology with the murine lung adenoma susceptibility 1 (Las1) protein—a candidate tumor suppressor gene implicated in lung tumorigenesis. Multiple, independent biochemical assays determined that IC97 interacts with both α- and β-tubulin subunits within the axoneme. I1-dynein assembly mutants suggest that IC97 interacts with both the IC138 and IC140 subunits within the I1-dynein motor complex and that IC97 is part of a regulatory complex that contains IC138. Microtubule sliding assays, using axonemes containing I1 dynein but devoid of IC97, show reduced microtubule sliding velocities that are not rescued by kinase inhibitors, revealing a critical role for IC97 in I1-dynein function and control of dynein-driven motility. PMID:19420136

  15. Dynein's Network of Chemomechanical Motor Cycles

    NASA Astrophysics Data System (ADS)

    Shen, Weibo; Wang, Ziqing; Wang, Guodong

    2012-07-01

    An eight-state network model of dynein's chemomechanical motor cycles is developed, in which the states of an effective single dynein head are represented by the number of ATP binding at the primary site and the number of ATP binding at other three secondary sites. The binding and unbinding of ATP, as well as the hydrolysis of ATP and the reverse process, are characterized by transition rates between certain states. Our results show that the stall force of dynein increases fast with ATP up to 1 mM ATP, beyond which it increases slowly to a saturated value, and that load and ATP concentration can adjust the step size of dynein, i.e., dynein can shift gears according to conditions. These results are in agreement with experiments [R. Mallik, B. C. Carter, S. A. Lex, S. J. King and S. P. Gross, Nature 427, 649 (2004)].

  16. Structural atlas of dynein motors at atomic resolution.

    PubMed

    Toda, Akiyuki; Tanaka, Hideaki; Kurisu, Genji

    2018-04-01

    Dynein motors are biologically important bio-nanomachines, and many atomic resolution structures of cytoplasmic dynein components from different organisms have been analyzed by X-ray crystallography, cryo-EM, and NMR spectroscopy. This review provides a historical perspective of structural studies of cytoplasmic and axonemal dynein including accessory proteins. We describe representative structural studies of every component of dynein and summarize them as a structural atlas that classifies the cytoplasmic and axonemal dyneins. Based on our review of all dynein structures in the Protein Data Bank, we raise two important points for understanding the two types of dynein motor and discuss the potential prospects of future structural studies.

  17. A mouse neurodegenerative dynein heavy chain mutation alters dynein motility and localization in Neurospora crassa.

    PubMed

    Sivagurunathan, Senthilkumar; Schnittker, Robert R; Nandini, Swaran; Plamann, Michael D; King, Stephen J

    2012-09-01

    Cytoplasmic dynein is responsible for the transport and delivery of cargoes in organisms ranging from humans to fungi. Dysfunction of dynein motor machinery due to mutations in dynein or its activating complex dynactin can result in one of several neurological diseases in mammals. The mouse Legs at odd angles (Loa) mutation in the tail domain of the dynein heavy chain has been shown to lead to progressive neurodegeneration in mice. The mechanism by which the Loa mutation affects dynein function is just beginning to be understood. In this work, we generated the dynein tail mutation observed in Loa mice into the Neurospora crassa genome and utilized cell biological and complementing biochemical approaches to characterize how that tail mutation affected dynein function. We determined that the Loa mutation exhibits several subtle defects upon dynein function in N. crassa that were not seen in mice, including alterations in dynein localization, impaired velocity of vesicle transport, and in the biochemical properties of purified motors. Our work provides new information on the role of the tail domain on dynein function and points out areas of future research that will be of interest to pursue in mammalian systems. 2012 Wiley Periodicals, Inc

  18. A Mouse Neurodegenerative Dynein Heavy Chain Mutation Alters Dynein Motility and Localization in Neurospora crassa

    PubMed Central

    Sivagurunathan, Senthilkumar; Schnittker, Robert R.; Nandini, Swaran; Plamann, Michael D.; King, Stephen J.

    2013-01-01

    Cytoplasmic dynein is responsible for the transport and delivery of cargoes in organisms ranging from humans to fungi. Dysfunction of dynein motor machinery due to mutations in dynein or its activating complex dynactin can result in one of several neurological diseases in mammals. The mouse Legs at odd angles (Loa) mutation in the tail domain of the dynein heavy chain has been shown to lead to progressive neurodegeneration in mice. The mechanism by which the Loa mutation affects dynein function is just beginning to be understood. In this work, we generated the dynein tail mutation observed in Loa mice into the Neurospora crassa genome and utilized cell biological and complementing biochemical approaches to characterize how that tail mutation affected dynein function. We determined that the Loa mutation exhibits several subtle defects upon dynein function in N. crassa that were not seen in mice, including alterations in dynein localization, impaired velocity of vesicle transport, and in the biochemical properties of purified motors. Our work provides new information on the role of the tail domain on dynein function and points out areas of future research that will be of interest to pursue in mammalian systems. PMID:22991199

  19. Ciliobrevins as tools for studying dynein motor function

    PubMed Central

    Roossien, Douglas H.; Miller, Kyle E.; Gallo, Gianluca

    2015-01-01

    Dyneins are a small class of molecular motors that bind to microtubules and walk toward their minus ends. They are essential for the transport and distribution of organelles, signaling complexes and cytoskeletal elements. In addition dyneins generate forces on microtubule arrays that power the beating of cilia and flagella, cell division, migration and growth cone motility. Classical approaches to the study of dynein function in axons involve the depletion of dynein, expression of mutant/truncated forms of the motor, or interference with accessory subunits. By necessity, these approaches require prolonged time periods for the expression or manipulation of cellular dynein levels. With the discovery of the ciliobrevins, a class of cell permeable small molecule inhibitors of dynein, it is now possible to acutely disrupt dynein both globally and locally. In this review, we briefly summarize recent work using ciliobrevins to inhibit dynein and discuss the insights ciliobrevins have provided about dynein function in various cell types with a focus on neurons. We temper this with a discussion of the need for studies that will elucidate the mechanism of action of ciliobrevin and as well as the need for experiments to further analyze the specificity of ciliobreviens for dynein. Although much remains to be learned about ciliobrevins, these small molecules are proving themselves to be valuable novel tools to assess the cellular functions of dynein. PMID:26217180

  20. X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3

    PubMed Central

    Olcese, Chiara; Patel, Mitali P.; Shoemark, Amelia; Kiviluoto, Santeri; Legendre, Marie; Williams, Hywel J.; Vaughan, Cara K.; Hayward, Jane; Goldenberg, Alice; Emes, Richard D.; Munye, Mustafa M.; Dyer, Laura; Cahill, Thomas; Bevillard, Jeremy; Gehrig, Corinne; Guipponi, Michel; Chantot, Sandra; Duquesnoy, Philippe; Thomas, Lucie; Jeanson, Ludovic; Copin, Bruno; Tamalet, Aline; Thauvin-Robinet, Christel; Papon, Jean- François; Garin, Antoine; Pin, Isabelle; Vera, Gabriella; Aurora, Paul; Fassad, Mahmoud R.; Jenkins, Lucy; Boustred, Christopher; Cullup, Thomas; Dixon, Mellisa; Onoufriadis, Alexandros; Bush, Andrew; Chung, Eddie M. K.; Antonarakis, Stylianos E.; Loebinger, Michael R.; Wilson, Robert; Armengot, Miguel; Escudier, Estelle; Hogg, Claire; Al-Turki, Saeed; Anderson, Carl; Antony, Dinu; Barroso, Inês; Beales, Philip L.; Bentham, Jamie; Bhattacharya, Shoumo; Carss, Keren; Chatterjee, Krishna; Cirak, Sebahattin; Cosgrove, Catherine; Allan, Daly; Durbin, Richard; Fitzpatrick, David; Floyd, Jamie; Foley, A. Reghan; Franklin, Chris; Futema, Marta; Humphries, Steve E.; Hurles, Matt; McCarthy, Shane; Muddyman, Dawn; Muntoni, Francesco; Parker, Victoria; Payne, Felicity; Plagnol, Vincent; Raymond, Lucy; Savage, David B.; Scambler, Peter J.; Schmidts, Miriam; Semple, Robert; Serra, Eva; Stalker, Jim; van Kogelenberg, Margriet; Vijayarangakannan, Parthiban; Walter, Klaudia; Amselem, Serge; Sun, Zhaoxia; Bartoloni, Lucia; Blouin, Jean-Louis; Mitchison, Hannah M.

    2017-01-01

    By moving essential body fluids and molecules, motile cilia and flagella govern respiratory mucociliary clearance, laterality determination and the transport of gametes and cerebrospinal fluid. Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder frequently caused by non-assembly of dynein arm motors into cilia and flagella axonemes. Before their import into cilia and flagella, multi-subunit axonemal dynein arms are thought to be stabilized and pre-assembled in the cytoplasm through a DNAAF2–DNAAF4–HSP90 complex akin to the HSP90 co-chaperone R2TP complex. Here, we demonstrate that large genomic deletions as well as point mutations involving PIH1D3 are responsible for an X-linked form of PCD causing disruption of early axonemal dynein assembly. We propose that PIH1D3, a protein that emerges as a new player of the cytoplasmic pre-assembly pathway, is part of a complementary conserved R2TP-like HSP90 co-chaperone complex, the loss of which affects assembly of a subset of inner arm dyneins. PMID:28176794

  1. X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3.

    PubMed

    Olcese, Chiara; Patel, Mitali P; Shoemark, Amelia; Kiviluoto, Santeri; Legendre, Marie; Williams, Hywel J; Vaughan, Cara K; Hayward, Jane; Goldenberg, Alice; Emes, Richard D; Munye, Mustafa M; Dyer, Laura; Cahill, Thomas; Bevillard, Jeremy; Gehrig, Corinne; Guipponi, Michel; Chantot, Sandra; Duquesnoy, Philippe; Thomas, Lucie; Jeanson, Ludovic; Copin, Bruno; Tamalet, Aline; Thauvin-Robinet, Christel; Papon, Jean-François; Garin, Antoine; Pin, Isabelle; Vera, Gabriella; Aurora, Paul; Fassad, Mahmoud R; Jenkins, Lucy; Boustred, Christopher; Cullup, Thomas; Dixon, Mellisa; Onoufriadis, Alexandros; Bush, Andrew; Chung, Eddie M K; Antonarakis, Stylianos E; Loebinger, Michael R; Wilson, Robert; Armengot, Miguel; Escudier, Estelle; Hogg, Claire; Amselem, Serge; Sun, Zhaoxia; Bartoloni, Lucia; Blouin, Jean-Louis; Mitchison, Hannah M

    2017-02-08

    By moving essential body fluids and molecules, motile cilia and flagella govern respiratory mucociliary clearance, laterality determination and the transport of gametes and cerebrospinal fluid. Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder frequently caused by non-assembly of dynein arm motors into cilia and flagella axonemes. Before their import into cilia and flagella, multi-subunit axonemal dynein arms are thought to be stabilized and pre-assembled in the cytoplasm through a DNAAF2-DNAAF4-HSP90 complex akin to the HSP90 co-chaperone R2TP complex. Here, we demonstrate that large genomic deletions as well as point mutations involving PIH1D3 are responsible for an X-linked form of PCD causing disruption of early axonemal dynein assembly. We propose that PIH1D3, a protein that emerges as a new player of the cytoplasmic pre-assembly pathway, is part of a complementary conserved R2TP-like HSP90 co-chaperone complex, the loss of which affects assembly of a subset of inner arm dyneins.

  2. The dynein cortical anchor Num1 activates dynein motility by relieving Pac1/LIS1-mediated inhibition

    PubMed Central

    Lammers, Lindsay G.

    2015-01-01

    Cortically anchored dynein orients the spindle through interactions with astral microtubules. In budding yeast, dynein is offloaded to Num1 receptors from microtubule plus ends. Rather than walking toward minus ends, dynein remains associated with plus ends due in part to its association with Pac1/LIS1, an inhibitor of dynein motility. The mechanism by which dynein is switched from “off” at the plus ends to “on” at the cell cortex remains unknown. Here, we show that overexpression of the coiled-coil domain of Num1 specifically depletes dynein–dynactin–Pac1/LIS1 complexes from microtubule plus ends and reduces dynein-Pac1/LIS1 colocalization. Depletion of dynein from plus ends requires its microtubule-binding domain, suggesting that motility is required. An enhanced Pac1/LIS1 affinity mutant of dynein or overexpression of Pac1/LIS1 rescues dynein plus end depletion. Live-cell imaging reveals minus end–directed dynein–dynactin motility along microtubules upon overexpression of the coiled-coil domain of Num1, an event that is not observed in wild-type cells. Our findings indicate that dynein activity is directly switched “on” by Num1, which induces Pac1/LIS1 removal. PMID:26483554

  3. Quantitative Analysis of Pac1/LIS1-mediated Dynein Targeting: Implications for Regulation of Dynein Activity in Budding Yeast

    PubMed Central

    Markus, Steven M.; Plevock, Karen M.; St. Germain, Bryan J.; Punch, Jesse J.; Meaden, Christopher W.; Lee, Wei-Lih

    2011-01-01

    LIS1 is a critical regulator of dynein function during mitosis and organelle transport. Here, we investigated how Pac1, the budding yeast LIS1 homologue, regulates dynein targeting and activity during nuclear migration. We show that Pac1 and Dyn1 (dynein heavy chain) are dependent upon each other and upon Bik1 (budding yeast CLIP-170 homologue) for plus end localization, whereas Bik1 is independent of either. Dyn1, Pac1 and Bik1 interact in vivo at the plus ends, where an excess amount of Bik1 recruits approximately equal amounts of Pac1 and Dyn1. Overexpression of Pac1 enhanced plus end targeting of Dyn1 and vice versa, while affinity-purification of Dyn1 revealed that it exists in a complex with Pac1 in the absence of Bik1, leading us to conclude that the Pac1-Dyn1 complex preassembles in the cytoplasm prior to loading onto Bik1-decorated plus ends. Strikingly, we found that Pac1-overexpression augments cortical dynein activity through a mechanism distinct from loss of She1, a negative regulator of dynein-dynactin association. While Pac1-overexpression enhances the frequency of cortical targeting for dynein and dynactin, the stoichiometry of these complexes remains relatively unchanged at the plus ends compared to that in wild-type cells (~3 dynein to 1 dynactin). Loss of She1, however, enhances dynein-dynactin association at the plus ends and the cell cortex, resulting in an apparent 1:1 stoichiometry. Our results reveal differential regulation of cortical dynein activity by She1 and Pac1, and provide a potentially new regulatory step in the off-loading model for dynein function. PMID:21294277

  4. Loss-of-Function Mutations in a Human Gene Related to Chlamydomonas reinhardtii Dynein IC78 Result in Primary Ciliary Dyskinesia

    PubMed Central

    Pennarun, Gaëlle; Escudier, Estelle; Chapelin, Catherine; Bridoux, Anne-Marie; Cacheux, Valère; Roger, Gilles; Clément, Annick; Goossens, Michel; Amselem, Serge; Duriez, Bénédicte

    1999-01-01

    Summary Primary ciliary dyskinesia (PCD) is a group of heterogeneous disorders of unknown origin, usually inherited as an autosomal recessive trait. Its phenotype is characterized by axonemal abnormalities of respiratory cilia and sperm tails leading to bronchiectasis and sinusitis, which are sometimes associated with situs inversus (Kartagener syndrome) and male sterility. The main ciliary defect in PCD is an absence of dynein arms. We have isolated the first gene involved in PCD, using a candidate-gene approach developed on the basis of documented abnormalities of immotile strains of Chlamydomonas reinhardtii, which carry axonemal ultrastructural defects reminiscent of PCD. Taking advantage of the evolutionary conservation of genes encoding axonemal proteins, we have isolated a human sequence (DNAI1) related to IC78, a C. reinhardtii gene encoding a dynein intermediate chain in which mutations are associated with the absence of outer dynein arms. DNAI1 is highly expressed in trachea and testis and is composed of 20 exons located at 9p13-p21. Two loss-of-function mutations of DNAI1 have been identified in a patient with PCD characterized by immotile respiratory cilia lacking outer dynein arms. In addition, we excluded linkage between this gene and similar PCD phenotypes in five other affected families, providing a clear demonstration of locus heterogeneity. These data reveal the critical role of DNAI1 in the development of human axonemal structures and open up new means for identification of additional genes involved in related developmental defects. PMID:10577904

  5. To prohibit the deployment of United States Armed Forces in support of a United Nations or mutual security treaty military operation absent express prior statutory authorization from Congress for such deployment, and for other purposes.

    THOMAS, 113th Congress

    Rep. Jones, Walter B., Jr. [R-NC-3

    2013-06-25

    House - 06/25/2013 Referred to the Committee on Foreign Affairs, and in addition to the Committee on Armed Services, for a period to be subsequently determined by the Speaker, in each case for consideration of such provisions as fall within the jurisdiction of the committee concerned. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  6. Bidirectional helical motility of cytoplasmic dynein around microtubules

    PubMed Central

    Can, Sinan; Dewitt, Mark A; Yildiz, Ahmet

    2014-01-01

    Cytoplasmic dynein is a molecular motor responsible for minus-end-directed cargo transport along microtubules (MTs). Dynein motility has previously been studied on surface-immobilized MTs in vitro, which constrains the motors to move in two dimensions. In this study, we explored dynein motility in three dimensions using an MT bridge assay. We found that dynein moves in a helical trajectory around the MT, demonstrating that it generates torque during cargo transport. Unlike other cytoskeletal motors that produce torque in a specific direction, dynein generates torque in either direction, resulting in bidirectional helical motility. Dynein has a net preference to move along a right-handed helical path, suggesting that the heads tend to bind to the closest tubulin binding site in the forward direction when taking sideways steps. This bidirectional helical motility may allow dynein to avoid roadblocks in dense cytoplasmic environments during cargo transport. DOI: http://dx.doi.org/10.7554/eLife.03205.001 PMID:25069614

  7. The human cytoplasmic dynein interactome reveals novel activators of motility

    PubMed Central

    Redwine, William B; DeSantis, Morgan E; Hollyer, Ian; Htet, Zaw Min; Tran, Phuoc Tien; Swanson, Selene K; Florens, Laurence; Washburn, Michael P; Reck-Peterson, Samara L

    2017-01-01

    In human cells, cytoplasmic dynein-1 is essential for long-distance transport of many cargos, including organelles, RNAs, proteins, and viruses, towards microtubule minus ends. To understand how a single motor achieves cargo specificity, we identified the human dynein interactome by attaching a promiscuous biotin ligase (‘BioID’) to seven components of the dynein machinery, including a subunit of the essential cofactor dynactin. This method reported spatial information about the large cytosolic dynein/dynactin complex in living cells. To achieve maximal motile activity and to bind its cargos, human dynein/dynactin requires ‘activators’, of which only five have been described. We developed methods to identify new activators in our BioID data, and discovered that ninein and ninein-like are a new family of dynein activators. Analysis of the protein interactomes for six activators, including ninein and ninein-like, suggests that each dynein activator has multiple cargos. DOI: http://dx.doi.org/10.7554/eLife.28257.001 PMID:28718761

  8. Lis1 regulates dynein by sterically blocking its mechanochemical cycle

    PubMed Central

    Toropova, Katerina; Zou, Sirui; Roberts, Anthony J; Redwine, William B; Goodman, Brian S; Reck-Peterson, Samara L; Leschziner, Andres E

    2014-01-01

    Regulation of cytoplasmic dynein's motor activity is essential for diverse eukaryotic functions, including cell division, intracellular transport, and brain development. The dynein regulator Lis1 is known to keep dynein bound to microtubules; however, how this is accomplished mechanistically remains unknown. We have used three-dimensional electron microscopy, single-molecule imaging, biochemistry, and in vivo assays to help establish this mechanism. The three-dimensional structure of the dynein–Lis1 complex shows that binding of Lis1 to dynein's AAA+ ring sterically prevents dynein's main mechanical element, the ‘linker’, from completing its normal conformational cycle. Single-molecule experiments show that eliminating this block by shortening the linker to a point where it can physically bypass Lis1 renders single dynein motors insensitive to regulation by Lis1. Our data reveal that Lis1 keeps dynein in a persistent microtubule-bound state by directly blocking the progression of its mechanochemical cycle. DOI: http://dx.doi.org/10.7554/eLife.03372.001 PMID:25380312

  9. Calaxin drives sperm chemotaxis by Ca2+-mediated direct modulation of a dynein motor

    PubMed Central

    Mizuno, Katsutoshi; Shiba, Kogiku; Okai, Masahiko; Takahashi, Yusuke; Shitaka, Yuji; Oiwa, Kazuhiro; Tanokura, Masaru; Inaba, Kazuo

    2012-01-01

    Sperm chemotaxis occurs widely in animals and plants and plays an important role in the success of fertilization. Several studies have recently demonstrated that Ca2+ influx through specific Ca2+ channels is a prerequisite for sperm chemotactic movement. However, the regulator that modulates flagellar movement in response to Ca2+ is unknown. Here we show that a neuronal calcium sensor, calaxin, directly acts on outer-arm dynein and regulates specific flagellar movement during sperm chemotaxis. Calaxin inhibition resulted in significant loss of sperm chemotactic movement, despite normal increases in intracellular calcium concentration. Using a demembranated sperm model, we demonstrate that calaxin is essential for generation and propagation of Ca2+-induced asymmetric flagellar bending. An in vitro motility assay revealed that calaxin directly suppressed the velocity of microtubule sliding by outer-arm dynein at high Ca2+ concentrations. This study describes the missing link between chemoattractant-mediated Ca2+ signaling and motor-driven microtubule sliding during sperm chemotaxis. PMID:23169663

  10. Monte Carlo modeling of single-molecule cytoplasmic dynein.

    PubMed

    Singh, Manoranjan P; Mallik, Roop; Gross, Steven P; Yu, Clare C

    2005-08-23

    Molecular motors are responsible for active transport and organization in the cell, underlying an enormous number of crucial biological processes. Dynein is more complicated in its structure and function than other motors. Recent experiments have found that, unlike other motors, dynein can take different size steps along microtubules depending on load and ATP concentration. We use Monte Carlo simulations to model the molecular motor function of cytoplasmic dynein at the single-molecule level. The theory relates dynein's enzymatic properties to its mechanical force production. Our simulations reproduce the main features of recent single-molecule experiments that found a discrete distribution of dynein step sizes, depending on load and ATP concentration. The model reproduces the large steps found experimentally under high ATP and no load by assuming that the ATP binding affinities at the secondary sites decrease as the number of ATP bound to these sites increases. Additionally, to capture the essential features of the step-size distribution at very low ATP concentration and no load, the ATP hydrolysis of the primary site must be dramatically reduced when none of the secondary sites have ATP bound to them. We make testable predictions that should guide future experiments related to dynein function.

  11. "Absent Data, Absent Women": Gender and Higher Education Leadership

    ERIC Educational Resources Information Center

    Aiston, Sarah Jane; Yang, Zi

    2017-01-01

    The study of the position, status and experience of women academics has in recent decades attracted a great deal of scholarly attention. The literature is characterized by what might be referred to as the "absent women" discourse, namely the underrepresentation of women in the highest positions in the sector, and is dominated by research…

  12. Dynein-mediated trafficking negatively regulates LET-23 EGFR signaling

    PubMed Central

    Skorobogata, Olga; Meng, Jassy; Gauthier, Kimberley; Rocheleau, Christian E.

    2016-01-01

    Epidermal growth factor receptor (EGFR) signaling is essential for animal development, and increased signaling underlies many human cancers. Identifying the genes and cellular processes that regulate EGFR signaling in vivo will help to elucidate how this pathway can become inappropriately activated. Caenorhabditis elegans vulva development provides an in vivo model to genetically dissect EGFR signaling. Here we identified a mutation in dhc-1, the heavy chain of the cytoplasmic dynein minus end–directed microtubule motor, in a genetic screen for regulators of EGFR signaling. Despite the many cellular functions of dynein, DHC-1 is a strong negative regulator of EGFR signaling during vulva induction. DHC-1 is required in the signal-receiving cell and genetically functions upstream or in parallel to LET-23 EGFR. LET-23 EGFR accumulates in cytoplasmic foci in dhc-1 mutants, consistent with mammalian cell studies in which dynein is shown to regulate late endosome trafficking of EGFR with the Rab7 GTPase. However, we found different distributions of LET-23 EGFR foci in rab-7 versus dhc-1 mutants, suggesting that dynein functions at an earlier step of LET-23 EGFR trafficking to the lysosome than RAB-7. Our results demonstrate an in vivo role for dynein in limiting LET-23 EGFR signaling via endosomal trafficking. PMID:27654944

  13. Genetic analysis of the cytoplasmic dynein subunit families.

    PubMed

    Pfister, K Kevin; Shah, Paresh R; Hummerich, Holger; Russ, Andreas; Cotton, James; Annuar, Azlina Ahmad; King, Stephen M; Fisher, Elizabeth M C

    2006-01-01

    Cytoplasmic dyneins, the principal microtubule minus-end-directed motor proteins of the cell, are involved in many essential cellular processes. The major form of this enzyme is a complex of at least six protein subunits, and in mammals all but one of the subunits are encoded by at least two genes. Here we review current knowledge concerning the subunits, their interactions, and their functional roles as derived from biochemical and genetic analyses. We also carried out extensive database searches to look for new genes and to clarify anomalies in the databases. Our analysis documents evolutionary relationships among the dynein subunits of mammals and other model organisms, and sheds new light on the role of this diverse group of proteins, highlighting the existence of two cytoplasmic dynein complexes with distinct cellular roles.

  14. Genetic Analysis of the Cytoplasmic Dynein Subunit Families

    PubMed Central

    Pfister, K. Kevin; Shah, Paresh R; Hummerich, Holger; Russ, Andreas; Cotton, James; Annuar, Azlina Ahmad; King, Stephen M; Fisher, Elizabeth M. C

    2006-01-01

    Cytoplasmic dyneins, the principal microtubule minus-end-directed motor proteins of the cell, are involved in many essential cellular processes. The major form of this enzyme is a complex of at least six protein subunits, and in mammals all but one of the subunits are encoded by at least two genes. Here we review current knowledge concerning the subunits, their interactions, and their functional roles as derived from biochemical and genetic analyses. We also carried out extensive database searches to look for new genes and to clarify anomalies in the databases. Our analysis documents evolutionary relationships among the dynein subunits of mammals and other model organisms, and sheds new light on the role of this diverse group of proteins, highlighting the existence of two cytoplasmic dynein complexes with distinct cellular roles. PMID:16440056

  15. Dynein Regulators Are Important for Ecotropic Murine Leukemia Virus Infection

    PubMed Central

    Valle-Tenney, Roger; Opazo, Tatiana; Cancino, Jorge; Goff, Stephen P.

    2016-01-01

    ABSTRACT During the early steps of infection, retroviruses must direct the movement of the viral genome into the nucleus to complete their replication cycle. This process is mediated by cellular proteins that interact first with the reverse transcription complex and later with the preintegration complex (PIC), allowing it to reach and enter the nucleus. For simple retroviruses, such as murine leukemia virus (MLV), the identities of the cellular proteins involved in trafficking of the PIC in infection are unknown. To identify cellular proteins that interact with the MLV PIC, we developed a replication-competent MLV in which the integrase protein was tagged with a FLAG epitope. Using a combination of immunoprecipitation and mass spectrometry, we established that the microtubule motor dynein regulator DCTN2/p50/dynamitin interacts with the MLV preintegration complex early in infection, suggesting a direct interaction between the incoming viral particles and the dynein complex regulators. Further experiments showed that RNA interference (RNAi)-mediated silencing of either DCTN2/p50/dynamitin or another dynein regulator, NudEL, profoundly reduced the efficiency of infection by ecotropic, but not amphotropic, MLV reporters. We propose that the cytoplasmic dynein regulators are a critical component of the host machinery needed for infection by the retroviruses entering the cell via the ecotropic envelope pathway. IMPORTANCE Retroviruses must access the chromatin of host cells to integrate the viral DNA, but before this crucial event, they must reach the nucleus. The movement through the cytoplasm—a crowded environment where diffusion is slow—is thought to utilize retrograde transport along the microtubule network by the dynein complex. Different viruses use different components of this multisubunit complex. We found that the preintegration complex of murine leukemia virus (MLV) interacts with the dynein complex and that regulators of this complex are essential for

  16. Cytoplasmic Dynein Regulation by Subunit Heterogeneity and Its Role in Apical Transport

    PubMed Central

    Tai, Andrew W.; Chuang, Jen-Zen; Sung, Ching-Hwa

    2001-01-01

    Despite the existence of multiple subunit isoforms for the microtubule motor cytoplasmic dynein, it has not yet been directly shown that dynein complexes with different compositions exhibit different properties. The 14-kD dynein light chain Tctex-1, but not its homologue RP3, binds directly to rhodopsin's cytoplasmic COOH-terminal tail, which encodes an apical targeting determinant in polarized epithelial Madin-Darby canine kidney (MDCK) cells. We demonstrate that Tctex-1 and RP3 compete for binding to dynein intermediate chain and that overexpressed RP3 displaces endogenous Tctex-1 from dynein complexes in MDCK cells. Furthermore, replacement of Tctex-1 by RP3 selectively disrupts the translocation of rhodopsin to the MDCK apical surface. These results directly show that cytoplasmic dynein function can be regulated by its subunit composition and that cytoplasmic dynein is essential for at least one mode of apical transport in polarized epithelia. PMID:11425878

  17. NudEL targets dynein to microtubule ends through LIS1

    PubMed Central

    Li, Jun; Lee, Wei-Lih; Cooper, John A.

    2006-01-01

    Dynein is a minus-end-directed microtubule motor with critical roles in mitosis, membrane transport and intracellular transport. Several proteins regulate dynein activity, including dynactin1, LIS1 (refs 2, 3) and NudEL (NudE-like)2,4–8. Here, we identify a NUDEL homologue in budding yeast and name it Ndl1. The ndl1Δ null mutant shows decreased targeting of dynein to microtubule plus ends, an essential element of the model for dynein function. We find that Ndl1 regulates dynein targeting through LIS1, with which it interacts biochemically, but not through CLIP170, another plus-end protein involved in dynein targeting9. Ndl1 is found at far fewer microtubule ends than are LIS1 and dynein. However, when Ndl1 is present at a plus end, the molar amount of Ndl1 approaches that of LIS1 and dynein. We propose a model in which Ndl1 binds transiently to the plus end to promote targeting of LIS1, which cooperatively recruits dynein. PMID:15965467

  18. NudEL targets dynein to microtubule ends through LIS1.

    PubMed

    Li, Jun; Lee, Wei-Lih; Cooper, John A

    2005-07-01

    Dynein is a minus-end-directed microtubule motor with critical roles in mitosis, membrane transport and intracellular transport. Several proteins regulate dynein activity, including dynactin, LIS1 (refs 2, 3) and NudEL (NudE-like). Here, we identify a NUDEL homologue in budding yeast and name it Ndl1. The ndl1delta null mutant shows decreased targeting of dynein to microtubule plus ends, an essential element of the model for dynein function. We find that Ndl1 regulates dynein targeting through LIS1, with which it interacts biochemically, but not through CLIP170, another plus-end protein involved in dynein targeting. Ndl1 is found at far fewer microtubule ends than are LIS1 and dynein. However, when Ndl1 is present at a plus end, the molar amount of Ndl1 approaches that of LIS1 and dynein. We propose a model in which Ndl1 binds transiently to the plus end to promote targeting of LIS1, which cooperatively recruits dynein.

  19. A structural analysis of the AAA+ domains in Saccharomyces cerevisiae cytoplasmic dynein

    PubMed Central

    Gleave, Emma S.; Schmidt, Helgo; Carter, Andrew P.

    2014-01-01

    Dyneins are large protein complexes that act as microtubule based molecular motors. The dynein heavy chain contains a motor domain which is a member of the AAA+ protein family (ATPases Associated with diverse cellular Activities). Proteins of the AAA+ family show a diverse range of functionalities, but share a related core AAA+ domain, which often assembles into hexameric rings. Dynein is unusual because it has all six AAA+ domains linked together, in one long polypeptide. The dynein motor domain generates movement by coupling ATP driven conformational changes in the AAA+ ring to the swing of a motile element called the linker. Dynein binds to its microtubule track via a long antiparallel coiled-coil stalk that emanates from the AAA+ ring. Recently the first high resolution structures of the dynein motor domain were published. Here we provide a detailed structural analysis of the six AAA+ domains using our Saccharomycescerevisiae crystal structure. We describe how structural similarities in the dynein AAA+ domains suggest they share a common evolutionary origin. We analyse how the different AAA+ domains have diverged from each other. We discuss how this is related to the function of dynein as a motor protein and how the AAA+ domains of dynein compare to those of other AAA+ proteins. PMID:24680784

  20. Dynactin functions as both a dynamic tether and brake during dynein-driven motility

    NASA Astrophysics Data System (ADS)

    Ayloo, Swathi; Lazarus, Jacob E.; Dodda, Aditya; Tokito, Mariko; Ostap, E. Michael; Holzbaur, Erika L. F.

    2014-09-01

    Dynactin is an essential cofactor for most cellular functions of the microtubule motor cytoplasmic dynein, but the mechanism by which dynactin activates dynein remains unclear. Here we use single molecule approaches to investigate dynein regulation by the dynactin subunit p150Glued. We investigate the formation and motility of a dynein-p150Glued co-complex using dual-colour total internal reflection fluorescence microscopy. p150Glued recruits and tethers dynein to the microtubule in a concentration-dependent manner. Single molecule imaging of motility in cell extracts demonstrates that the CAP-Gly domain of p150Glued decreases the detachment rate of the dynein-dynactin complex from the microtubule and also acts as a brake to slow the dynein motor. Consistent with this important role, two neurodegenerative disease-causing mutations in the CAP-Gly domain abrogate these functions in our assays. Together, these observations support a model in which dynactin enhances the initial recruitment of dynein onto microtubules and promotes the sustained engagement of dynein with its cytoskeletal track.

  1. A structural analysis of the AAA+ domains in Saccharomyces cerevisiae cytoplasmic dynein.

    PubMed

    Gleave, Emma S; Schmidt, Helgo; Carter, Andrew P

    2014-06-01

    Dyneins are large protein complexes that act as microtubule based molecular motors. The dynein heavy chain contains a motor domain which is a member of the AAA+ protein family (ATPases Associated with diverse cellular Activities). Proteins of the AAA+ family show a diverse range of functionalities, but share a related core AAA+ domain, which often assembles into hexameric rings. Dynein is unusual because it has all six AAA+ domains linked together, in one long polypeptide. The dynein motor domain generates movement by coupling ATP driven conformational changes in the AAA+ ring to the swing of a motile element called the linker. Dynein binds to its microtubule track via a long antiparallel coiled-coil stalk that emanates from the AAA+ ring. Recently the first high resolution structures of the dynein motor domain were published. Here we provide a detailed structural analysis of the six AAA+ domains using our Saccharomycescerevisiae crystal structure. We describe how structural similarities in the dynein AAA+ domains suggest they share a common evolutionary origin. We analyse how the different AAA+ domains have diverged from each other. We discuss how this is related to the function of dynein as a motor protein and how the AAA+ domains of dynein compare to those of other AAA+ proteins. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Lissencephaly-1 is a context-dependent regulator of the human dynein complex

    PubMed Central

    Baumbach, Janina; Murthy, Andal; McClintock, Mark A; Dix, Carly I; Zalyte, Ruta; Hoang, Ha Thi; Bullock, Simon L

    2017-01-01

    The cytoplasmic dynein-1 (dynein) motor plays a central role in microtubule organisation and cargo transport. These functions are spatially regulated by association of dynein and its accessory complex dynactin with dynamic microtubule plus ends. Here, we elucidate in vitro the roles of dynactin, end-binding protein-1 (EB1) and Lissencephaly-1 (LIS1) in the interaction of end tracking and minus end-directed human dynein complexes with these sites. LIS1 promotes dynactin-dependent tracking of dynein on both growing and shrinking plus ends. LIS1 also increases the frequency and velocity of processive dynein movements that are activated by complex formation with dynactin and a cargo adaptor. This stimulatory effect of LIS1 contrasts sharply with its documented ability to inhibit the activity of isolated dyneins. Collectively, our findings shed light on how mammalian dynein complexes associate with dynamic microtubules and help clarify how LIS1 promotes the plus-end localisation and cargo transport functions of dynein in vivo. DOI: http://dx.doi.org/10.7554/eLife.21768.001 PMID:28406398

  3. The Light Intermediate Chain 2 Subpopulation of Dynein Regulates Mitotic Spindle Orientation.

    PubMed

    Mahale, Sagar; Kumar, Megha; Sharma, Amit; Babu, Aswini; Ranjan, Shashi; Sachidanandan, Chetana; Mylavarapu, Sivaram V S

    2016-12-23

    Cytoplasmic dynein 1 is a multi-protein intracellular motor essential for mediating several mitotic functions, including the establishment of proper spindle orientation. The functional relevance and mechanistic distinctions between two discrete dynein subpopulations distinguished only by Light Intermediate Chain (LIC) homologues, LIC1 and LIC2 is unknown during mitosis. Here, we identify LIC2-dynein as the major mediator of proper spindle orientation and uncover its underlying molecular mechanism. Cortically localized dynein, essential for maintaining correct spindle orientation, consists majorly of LIC2-dynein, which interacts with cortical 14-3-3 ε- ζ and Par3, conserved proteins required for orienting the spindle. LIC2-dynein is also responsible for the majority of dynein-mediated asymmetric poleward transport of NuMA, helping focus microtubule minus ends. In addition, LIC2-dynein dominates in equatorially aligning chromosomes at metaphase and in regulating mitotic spindle length. Key mitotic functions of LIC2 were remarkably conserved in and essential for early embryonic divisions and development in zebrafish. Thus LIC2-dynein exclusively engages with two major cortical pathways to govern spindle orientation. Overall, we identify a novel selectivity of molecular interactions between the two LICs in mitosis as the underlying basis for their uneven distribution of labour in ensuring proper spindle orientation.

  4. BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular structures

    PubMed Central

    Splinter, Daniël; Razafsky, David S.; Schlager, Max A.; Serra-Marques, Andrea; Grigoriev, Ilya; Demmers, Jeroen; Keijzer, Nanda; Jiang, Kai; Poser, Ina; Hyman, Anthony A.; Hoogenraad, Casper C.; King, Stephen J.; Akhmanova, Anna

    2012-01-01

    Cytoplasmic dynein is the major microtubule minus-end–directed cellular motor. Most dynein activities require dynactin, but the mechanisms regulating cargo-dependent dynein–dynactin interaction are poorly understood. In this study, we focus on dynein–dynactin recruitment to cargo by the conserved motor adaptor Bicaudal D2 (BICD2). We show that dynein and dynactin depend on each other for BICD2-mediated targeting to cargo and that BICD2 N-terminus (BICD2-N) strongly promotes stable interaction between dynein and dynactin both in vitro and in vivo. Direct visualization of dynein in live cells indicates that by itself the triple BICD2-N–dynein–dynactin complex is unable to interact with either cargo or microtubules. However, tethering of BICD2-N to different membranes promotes their microtubule minus-end–directed motility. We further show that LIS1 is required for dynein-mediated transport induced by membrane tethering of BICD2-N and that LIS1 contributes to dynein accumulation at microtubule plus ends and BICD2-positive cellular structures. Our results demonstrate that dynein recruitment to cargo requires concerted action of multiple dynein cofactors. PMID:22956769

  5. Time-Dependent Measure of a Nano-Scale Force-Pulse Driven by the Axonemal Dynein Motors in Individual Live Sperm Cells

    SciTech Connect

    Allen, M J; Rudd, R E; McElfresh, M W

    Nano-scale mechanical forces generated by motor proteins are crucial to normal cellular and organismal functioning. The ability to measure and exploit such forces would be important to developing motile biomimetic nanodevices powered by biological motors for Nanomedicine. Axonemal dynein motors positioned inside the sperm flagellum drive microtubule sliding giving rise to rhythmic beating of the flagellum. This force-generating action makes it possible for the sperm cell to move through viscous media. Here we report new nano-scale information on how the propulsive force is generated by the sperm flagellum and how this force varies over time. Single cell recordings reveal discretemore » {approx}50 ms pulses oscillating with amplitude 9.8 {+-} 2.6 nN independent of pulse frequency (3.5-19.5 Hz). The average work carried out by each cell is 4.6 x 10{sup -16} J per pulse, equivalent to the hydrolysis of {approx}5,500 ATP molecules. The mechanochemical coupling at each active dynein head is {approx}2.2 pN/ATP, and {approx}3.9 pN per dynein arm, in agreement with previously published values obtained using different methods.« less

  6. Emergence of flagellar beating from the collective behavior of individual ATP-powered dyneins

    NASA Astrophysics Data System (ADS)

    Namdeo, S.; Onck, P. R.

    2016-10-01

    Flagella are hair-like projections from the surface of eukaryotic cells, and they play an important role in many cellular functions, such as cell-motility. The beating of flagella is enabled by their internal architecture, the axoneme, and is powered by a dense distribution of motor proteins, dyneins. The dyneins deliver the required mechanical work through the hydrolysis of ATP. Although the dynein-ATP cycle, the axoneme microstructure, and the flagellar-beating kinematics are well studied, their integration into a coherent picture of ATP-powered flagellar beating is still lacking. Here we show that a time-delayed negative-work-based switching mechanism is able to convert the individual sliding action of hundreds of dyneins into a regular overall beating pattern leading to propulsion. We developed a computational model based on a minimal representation of the axoneme consisting of two representative doublet microtubules connected by nexin links. The relative sliding of the microtubules is incorporated by modeling two groups of ATP-powered dyneins, each responsible for sliding in opposite directions. A time-delayed switching mechanism is postulated, which is key in converting the local individual sliding action of multiple dyneins into global beating. Our results demonstrate that an overall nonreciprocal beating pattern can emerge with time due to the spatial and temporal coordination of the individual dyneins. These findings provide insights in the fundamental working mechanism of axonemal dyneins and could possibly open new research directions in the field of flagellar motility.

  7. Emergence of flagellar beating from the collective behavior of individual ATP-powered dyneins.

    PubMed

    Namdeo, S; Onck, P R

    2016-10-01

    Flagella are hair-like projections from the surface of eukaryotic cells, and they play an important role in many cellular functions, such as cell-motility. The beating of flagella is enabled by their internal architecture, the axoneme, and is powered by a dense distribution of motor proteins, dyneins. The dyneins deliver the required mechanical work through the hydrolysis of ATP. Although the dynein-ATP cycle, the axoneme microstructure, and the flagellar-beating kinematics are well studied, their integration into a coherent picture of ATP-powered flagellar beating is still lacking. Here we show that a time-delayed negative-work-based switching mechanism is able to convert the individual sliding action of hundreds of dyneins into a regular overall beating pattern leading to propulsion. We developed a computational model based on a minimal representation of the axoneme consisting of two representative doublet microtubules connected by nexin links. The relative sliding of the microtubules is incorporated by modeling two groups of ATP-powered dyneins, each responsible for sliding in opposite directions. A time-delayed switching mechanism is postulated, which is key in converting the local individual sliding action of multiple dyneins into global beating. Our results demonstrate that an overall nonreciprocal beating pattern can emerge with time due to the spatial and temporal coordination of the individual dyneins. These findings provide insights in the fundamental working mechanism of axonemal dyneins and could possibly open new research directions in the field of flagellar motility.

  8. Huntingtin coordinates the dynein-mediated dynamic positioning of endosomes and lysosomes

    PubMed Central

    Caviston, Juliane P.; Zajac, Allison L.; Tokito, Mariko; Holzbaur, Erika L.F.

    2011-01-01

    Huntingtin (Htt) is a membrane-associated scaffolding protein that interacts with microtubule motors as well as actin-associated adaptor molecules. We examined a role for Htt in the dynein-mediated intracellular trafficking of endosomes and lysosomes. In HeLa cells depleted of either Htt or dynein, early, recycling, and late endosomes (LE)/lysosomes all become dispersed. Despite altered organelle localization, kinetic assays indicate only minor defects in intracellular trafficking. Expression of full-length Htt is required to restore organelle localization in Htt-depleted cells, supporting a role for Htt as a scaffold that promotes functional interactions along its length. In dynein-depleted cells, LE/lysosomes accumulate in tight patches near the cortex, apparently enmeshed by cortactin-positive actin filaments; Latrunculin B-treatment disperses these patches. Peripheral LE/lysosomes in dynein-depleted cells no longer colocalize with microtubules. Htt may be required for this off-loading, as the loss of microtubule association is not seen in Htt-depleted cells or in cells depleted of both dynein and Htt. Inhibition of kinesin-1 relocalizes peripheral LE/lysosomes induced by Htt depletion but not by dynein depletion, consistent with their detachment from microtubules upon dynein knockdown. Together, these data support a model of Htt as a facilitator of dynein-mediated trafficking that may regulate the cytoskeletal association of dynamic organelles. PMID:21169558

  9. Mutations in the Gene Encoding IFT Dynein Complex Component WDR34 Cause Jeune Asphyxiating Thoracic Dystrophy

    PubMed Central

    Schmidts, Miriam; Vodopiutz, Julia; Christou-Savina, Sonia; Cortés, Claudio R.; McInerney-Leo, Aideen M.; Emes, Richard D.; Arts, Heleen H.; Tüysüz, Beyhan; D’Silva, Jason; Leo, Paul J.; Giles, Tom C.; Oud, Machteld M.; Harris, Jessica A.; Koopmans, Marije; Marshall, Mhairi; Elçioglu, Nursel; Kuechler, Alma; Bockenhauer, Detlef; Moore, Anthony T.; Wilson, Louise C.; Janecke, Andreas R.; Hurles, Matthew E.; Emmet, Warren; Gardiner, Brooke; Streubel, Berthold; Dopita, Belinda; Zankl, Andreas; Kayserili, Hülya; Scambler, Peter J.; Brown, Matthew A.; Beales, Philip L.; Wicking, Carol; Duncan, Emma L.; Mitchison, Hannah M.

    2013-01-01

    Bidirectional (anterograde and retrograde) motor-based intraflagellar transport (IFT) governs cargo transport and delivery processes that are essential for primary cilia growth and maintenance and for hedgehog signaling functions. The IFT dynein-2 motor complex that regulates ciliary retrograde protein transport contains a heavy chain dynein ATPase/motor subunit, DYNC2H1, along with other less well functionally defined subunits. Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies. Here, by using exome sequencing and a targeted next-generation sequencing panel, we identified a total of 11 mutations in WDR34 in 9 families with the clinical diagnosis of Jeune syndrome (asphyxiating thoracic dystrophy). WDR34 encodes a WD40 repeat-containing protein orthologous to Chlamydomonas FAP133, a dynein intermediate chain associated with the retrograde intraflagellar transport motor. Three-dimensional protein modeling suggests that the identified mutations all affect residues critical for WDR34 protein-protein interactions. We find that WDR34 concentrates around the centrioles and basal bodies in mammalian cells, also showing axonemal staining. WDR34 coimmunoprecipitates with the dynein-1 light chain DYNLL1 in vitro, and mining of proteomics data suggests that WDR34 could represent a previously unrecognized link between the cytoplasmic dynein-1 and IFT dynein-2 motors. Together, these data show that WDR34 is critical for ciliary functions essential to normal development and survival, most probably as a previously unrecognized component of the mammalian dynein-IFT machinery. PMID:24183451

  10. Effect of fuel concentration and force on collective transport by a team of dynein motors

    PubMed Central

    Takshak, Anjneya; Roy, Tanushree; Tandaiya, Parag

    2016-01-01

    Abstract Motor proteins are essential components of intracellular transport inside eukaryotic cells. These protein molecules use chemical energy obtained from hydrolysis of ATP to produce mechanical forces required for transporting cargos inside cells, from one location to another, in a directed manner. Of these motors, cytoplasmic dynein is structurally more complex than other motor proteins involved in intracellular transport, as it shows force and fuel (ATP) concentration dependent step‐size. Cytoplasmic dynein motors are known to work in a team during cargo transport and force generation. Here, we use a complete Monte‐Carlo model of single dynein constrained by in vitro experiments, which includes the effect of both force and ATP on stepping as well as detachment of motors under force. We then use our complete Monte‐Carlo model of single dynein motor to understand collective cargo transport by a team of dynein motors, such as dependence of cargo travel distance and velocity on applied force and fuel concentration. In our model, cargos pulled by a team of dynein motors do not detach rapidly under higher forces, confirming the experimental observation of longer persistence time of dynein team on microtubule under higher forces. PMID:27727483

  11. Reconstitution of dynein transport to the microtubule plus end by kinesin

    PubMed Central

    Roberts, Anthony J; Goodman, Brian S; Reck-Peterson, Samara L

    2014-01-01

    Cytoplasmic dynein powers intracellular movement of cargo toward the microtubule minus end. The first step in a variety of dynein transport events is the targeting of dynein to the dynamic microtubule plus end, but the molecular mechanism underlying this spatial regulation is not understood. Here, we reconstitute dynein plus-end transport using purified proteins from S. cerevisiae and dissect the mechanism using single-molecule microscopy. We find that two proteins–homologs of Lis1 and Clip170–are sufficient to couple dynein to Kip2, a plus-end-directed kinesin. Dynein is transported to the plus end by Kip2, but is not a passive passenger, resisting its own plus-end-directed motion. Two microtubule-associated proteins, homologs of Clip170 and EB1, act as processivity factors for Kip2, helping it overcome dynein's intrinsic minus-end-directed motility. This reveals how a minimal system of proteins transports a molecular motor to the start of its track. DOI: http://dx.doi.org/10.7554/eLife.02641.001 PMID:24916158

  12. Hook is an adapter that coordinates kinesin-3 and dynein cargo attachment on early endosomes

    PubMed Central

    Bielska, Ewa; Schuster, Martin; Roger, Yvonne; Berepiki, Adokiye; Soanes, Darren M.; Talbot, Nicholas J.

    2014-01-01

    Bidirectional membrane trafficking along microtubules is mediated by kinesin-1, kinesin-3, and dynein. Several organelle-bound adapters for kinesin-1 and dynein have been reported that orchestrate their opposing activity. However, the coordination of kinesin-3/dynein-mediated transport is not understood. In this paper, we report that a Hook protein, Hok1, is essential for kinesin-3– and dynein-dependent early endosome (EE) motility in the fungus Ustilago maydis. Hok1 binds to EEs via its C-terminal region, where it forms a complex with homologues of human fused toes (FTS) and its interactor FTS- and Hook-interacting protein. A highly conserved N-terminal region is required to bind dynein and kinesin-3 to EEs. To change the direction of EE transport, kinesin-3 is released from organelles, and dynein binds subsequently. A chimaera of human Hook3 and Hok1 rescues the hok1 mutant phenotype, suggesting functional conservation between humans and fungi. We conclude that Hok1 is part of an evolutionarily conserved protein complex that regulates bidirectional EE trafficking by controlling attachment of both kinesin-3 and dynein. PMID:24637326

  13. Dynein-mediated pulling forces drive rapid mitotic spindle elongation in Ustilago maydis

    PubMed Central

    Fink, Gero; Schuchardt, Isabel; Colombelli, Julien; Stelzer, Ernst; Steinberg, Gero

    2006-01-01

    Spindle elongation segregates chromosomes and occurs in anaphase, an essential step in mitosis. Dynein-mediated pulling forces position the spindle, but their role in anaphase is a matter of debate. Here, we demonstrate that dynein is responsible for rapid spindle elongation in the model fungus Ustilago maydis. We show that initial slow elongation is supported by kinesin-5, which is located in the spindle mid-zone. When the spindle reaches ∼2 μm in length, the elongation rate increases four-fold. This coincides with the appearance of long and less-dynamic microtubules (MTs) at each pole that accumulate dynein at their tips. Laser-mediated nanosurgery revealed that these MTs exert pulling forces in control cells, but not in dynein mutants. In addition, dynein mutants undergo initial slow anaphase, but fail to establish less-dynamic MTs and do not perform rapid spindle elongation, suggesting that dynein drives anaphase B. This is most likely mediated by cortical sliding of astral MTs along stationary dynein, which is off-loaded from the MT plus-end to the cortex. PMID:17024185

  14. A split motor domain in a cytoplasmic dynein

    PubMed Central

    Straube, Anne; Enard, Wolfgang; Berner, Alexandra; Wedlich-Söldner, Roland; Kahmann, Regine; Steinberg, Gero

    2001-01-01

    The heavy chain of dynein forms a globular motor domain that tightly couples the ATP-cleavage region and the microtubule-binding site to transform chemical energy into motion along the cytoskeleton. Here we show that, in the fungus Ustilago maydis, two genes, dyn1 and dyn2, encode the dynein heavy chain. The putative ATPase region is provided by dyn1, while dyn2 includes the predicted microtubule-binding site. Both genes are located on different chromosomes, are transcribed into independent mRNAs and are translated into separate polypeptides. Both Dyn1 and Dyn2 co-immunoprecipitated and co-localized within growing cells, and Dyn1–Dyn2 fusion proteins partially rescued mutant phenotypes, suggesting that both polypeptides interact to form a complex. In cell extracts the Dyn1–Dyn2 complex dissociated, and microtubule affinity purification indicated that Dyn1 or associated polypeptides bind microtubules independently of Dyn2. Both Dyn1 and Dyn2 were essential for cell survival, and conditional mutants revealed a common role in nuclear migration, cell morphogenesis and microtubule organization, indicating that the Dyn1–Dyn2 complex serves multiple cellular functions. PMID:11566874

  15. Kinesin and Dynein Mechanics: Measurement Methods and Research Applications.

    PubMed

    Abraham, Zachary; Hawley, Emma; Hayosh, Daniel; Webster-Wood, Victoria A; Akkus, Ozan

    2018-02-01

    Motor proteins play critical roles in the normal function of cells and proper development of organisms. Among motor proteins, failings in the normal function of two types of proteins, kinesin and dynein, have been shown to lead many pathologies, including neurodegenerative diseases and cancers. As such, it is critical to researchers to understand the underlying mechanics and behaviors of these proteins, not only to shed light on how failures may lead to disease, but also to guide research toward novel treatment and nano-engineering solutions. To this end, many experimental techniques have been developed to measure the force and motility capabilities of these proteins. This review will (a) discuss such techniques, specifically microscopy, atomic force microscopy (AFM), optical trapping, and magnetic tweezers, and (b) the resulting nanomechanical properties of motor protein functions such as stalling force, velocity, and dependence on adenosine triphosophate (ATP) concentrations will be comparatively discussed. Additionally, this review will highlight the clinical importance of these proteins. Furthermore, as the understanding of the structure and function of motor proteins improves, novel applications are emerging in the field. Specifically, researchers have begun to modify the structure of existing proteins, thereby engineering novel elements to alter and improve native motor protein function, or even allow the motor proteins to perform entirely new tasks as parts of nanomachines. Kinesin and dynein are vital elements for the proper function of cells. While many exciting experiments have shed light on their function, mechanics, and applications, additional research is needed to completely understand their behavior.

  16. Microtubule-dependent path to the cell cortex for cytoplasmic dynein in mitotic spindle orientation

    PubMed Central

    Markus, Steven M.; Lee, Wei-Lih

    2011-01-01

    During animal development, microtubules (MTs) play a major role in directing cellular and subcellular patterning, impacting cell polarization and subcellular organization, thereby affecting cell fate determination and tissue architecture. In particular, when progenitor cells divide asymmetrically along an anterior-posterior or apical-basal axis, MTs must coordinate the position of the mitotic spindle with the site of cell division to ensure normal distribution of cell fate determinants and equal sequestration of genetic material into the two daughter cells. Emerging data from diverse model systems have led to the prevailing view that, during mitotic spindle positioning, polarity cues at the cell cortex signal for the recruitment of NuMA and the minus-end directed MT motor cytoplasmic dynein.1 The NuMA/dynein complex is believed to connect, in turn, to the mitotic spindle via astral MTs, thus aligning and tethering the spindle, but how this connection is achieved faithfully is unclear. Do astral MTs need to search for and then capture cortical NuMA/dynein? How does dynein capture the astral MTs emanating from the correct spindle pole? Recently, using the classical model of asymmetric cell division—budding yeast S. cerevisiae—we successfully demonstrated that astral MTs assume an active role in cortical dynein targeting, in that astral MTs utilize their distal plus ends to deliver dynein to the daughter cell cortex, the site where dynein activity is needed to perform its spindle alignment function. This observation introduced the novel idea that, during mitotic spindle orientation processes, polarity cues at the cell cortex may actually signal to prime the cortical receptors for MT-dependent dynein delivery. This model is consistent with the observation that dynein/dynactin accumulate prominently at the astral MT plus ends during metaphase in a wide range of cultured mammalian cells. PMID:22754610

  17. Congenitally absent lumbar pedicle: a reappraisal

    SciTech Connect

    Wortzman, G.; Steinhardt, M.I.

    1984-09-01

    Three patients who had a diagnosis of congenitally absent lumbar pedicle underwent CT examination. Findings showed that each patient had an aberrant hypoplastic pedicle plus a retroisthmic defect in their ipsilateral lamina rather than an absent pedicle. Axial CT was the diagnostic modality of choice; reformated images were of little value. The differential diagnosis to be considered from the findings of plain film radiography includes pediculate thinning, neoplastic disease, neurofibroma, mesodermal dysplasia associated with neurofibromatosis, and vascular anomalies.

  18. Kinetochore motors drive congression of peripheral polar chromosomes by overcoming random arm-ejection forces.

    PubMed

    Barisic, Marin; Aguiar, Paulo; Geley, Stephan; Maiato, Helder

    2014-12-01

    Accurate chromosome segregation during cell division in metazoans relies on proper chromosome congression at the equator. Chromosome congression is achieved after bi-orientation to both spindle poles shortly after nuclear envelope breakdown, or by the coordinated action of motor proteins that slide misaligned chromosomes along pre-existing spindle microtubules. These proteins include the minus-end-directed kinetochore motor dynein, and the plus-end-directed motors CENP-E at kinetochores and chromokinesins on chromosome arms. However, how these opposite and spatially distinct activities are coordinated to drive chromosome congression remains unknown. Here we used RNAi, chemical inhibition, kinetochore tracking and laser microsurgery to uncover the functional hierarchy between kinetochore and arm-associated motors, exclusively required for congression of peripheral polar chromosomes in human cells. We show that dynein poleward force counteracts chromokinesins to prevent stabilization of immature/incorrect end-on kinetochore-microtubule attachments and random ejection of polar chromosomes. At the poles, CENP-E becomes dominant over dynein and chromokinesins to bias chromosome ejection towards the equator. Thus, dynein and CENP-E at kinetochores drive congression of peripheral polar chromosomes by preventing arm-ejection forces mediated by chromokinesins from working in the wrong direction.

  19. Stopped in its tracks: negative regulation of the dynein motor by the yeast protein She1

    PubMed Central

    Moore, Jeffrey K.

    2013-01-01

    Summary How do cells direct the microtubule motor protein dynein to move cellular components to the right place at the right time? Recent studies in budding yeast shed light on a new mechanism for directing dynein, involving the protein She1. She1 restricts where and when dynein moves the nucleus and mitotic spindle. Experiments with purified proteins show that She1 binds to microtubules and inhibits dynein by stalling the motor on its track. Here I describe what we have learned so far about She1, based on a combination of genetic, cell biology, and biophysical approaches. These findings set the stage for further interrogation of the She1 mechanism, and raise the question of whether similar mechanisms exist in other species. PMID:23666903

  20. Single-molecule imaging of cytoplasmic dynein in vivo.

    PubMed

    Ananthanarayanan, Vaishnavi; Tolić, Iva M

    2015-01-01

    While early fluorescence microscopy experiments employing fluorescent probes afforded snapshots of the cell, the power of live-cell microscopy is required to understand complex dynamics in biological processes. The first successful cloning of green fluorescent protein in the 1990s paved the way for development of approaches that we now utilize for visualization in a living cell. In this chapter, we discuss a technique to observe fluorescently tagged single molecules in fission yeast. With a few simple modifications to the established total internal reflection fluorescence microscopy, cytoplasmic dynein molecules in the cytoplasm and on the microtubules can be visualized and their intracellular dynamics can be studied. We illustrate a technique to study motor behavior, which is not apparent in conventional ensemble studies of motors. In general, this technique can be employed to study single-molecule dynamics of fluorescently tagged proteins in the cell interior. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Dynein and dynactin leverage their bivalent character to form a high-affinity interaction.

    PubMed

    Siglin, Amanda E; Sun, Shangjin; Moore, Jeffrey K; Tan, Sarah; Poenie, Martin; Lear, James D; Polenova, Tatyana; Cooper, John A; Williams, John C

    2013-01-01

    Cytoplasmic dynein and dynactin participate in retrograde transport of organelles, checkpoint signaling and cell division. The principal subunits that mediate this interaction are the dynein intermediate chain (IC) and the dynactin p150(Glued); however, the interface and mechanism that regulates this interaction remains poorly defined. Herein, we use multiple methods to show the N-terminus of mammalian dynein IC, residues 10-44, is sufficient for binding p150(Glued). Consistent with this mapping, monoclonal antibodies that antagonize the dynein-dynactin interaction also bind to this region of the IC. Furthermore, double and triple alanine point mutations spanning residues 6 to 19 in the yeast IC homolog, Pac11, produce significant defects in spindle positioning. Using the same methods we show residues 381 to 530 of p150(Glued) form a minimal fragment that binds to the dynein IC. Sedimentation equilibrium experiments indicate that these individual fragments are predominantly monomeric, but admixtures of the IC and p150(Glued) fragments produce a 2:2 complex. This tetrameric complex is sensitive to salt, temperature and pH, suggesting that the binding is dominated by electrostatic interactions. Finally, circular dichroism (CD) experiments indicate that the N-terminus of the IC is disordered and becomes ordered upon binding p150(Glued). Taken together, the data indicate that the dynein-dynactin interaction proceeds through a disorder-to-order transition, leveraging its bivalent-bivalent character to form a high affinity, but readily reversible interaction.

  2. Cytoplasmic dynein binding, run length, and velocity are guided by long-range electrostatic interactions

    PubMed Central

    Li, Lin; Alper, Joshua; Alexov, Emil

    2016-01-01

    Dyneins are important molecular motors involved in many essential biological processes, including cargo transport along microtubules, mitosis, and in cilia. Dynein motility involves the coupling of microtubule binding and unbinding to a change in the configuration of the linker domain induced by ATP hydrolysis, which occur some 25 nm apart. This leaves the accuracy of dynein stepping relatively inaccurate and susceptible to thermal noise. Using multi-scale modeling with a computational focusing technique, we demonstrate that the microtubule forms an electrostatic funnel that guides the dynein’s microtubule binding domain (MTBD) as it finally docks to the precise, keyed binding location on the microtubule. Furthermore, we demonstrate that electrostatic component of the MTBD’s binding free energy is linearly correlated with the velocity and run length of dynein, and we use this linearity to predict the effect of mutating each glutamic and aspartic acid located in MTBD domain to alanine. Lastly, we show that the binding of dynein to the microtubule is associated with conformational changes involving several helices, and we localize flexible hinge points within the stalk helices. Taken all together, we demonstrate that long range electrostatic interactions bring a level of precision to an otherwise noisy dynein stepping process. PMID:27531742

  3. Kinetochore Dynein Is Required for Chromosome Motion and Congression Independent of the Spindle Checkpoint

    PubMed Central

    Yang, Zhenye; Tulu, U. Serdar; Wadsworth, Patricia; Rieder, Conly L.

    2008-01-01

    Summary During mitosis, the motor molecule cytoplasmic dynein plays key direct and indirect roles in organizing microtubules (MTs) into a functional spindle. At this time, dynein is also recruited to kinetochores, but its role or roles at these organelles remain vague, partly because inhibiting dynein globally disrupts spindle assembly [1-4]. However, dynein can be selectively depleted from kinetochores by disruption of ZW10 [5], and recent studies with this approach conclude that kinetochore-associated dynein (KD) functions to silence the spindle-assembly checkpoint (SAC) [6]. Here we use dynein-antibody microinjection and the RNAi of ZW10 to explore the role of KD in chromosome behavior during mitosis in mammals. We find that depleting or inhibiting KD prevents the rapid poleward motion of attaching kinetochores but not kinetochore fiber (K fiber) formation. However, after kinetochores attach to the spindle, KD is required for stabilizing kinetochore MTs, which it probably does by generating tension on the kinetochore, and in its absence, chromosome congression is defective. Finally, depleting KD reduces the velocity of anaphase chromosome motion by ∼40%, without affecting the rate of poleward MT flux. Thus, in addition to its role in silencing the SAC, KD is important for forming and stabilizing K fibers and in powering chromosome motion. PMID:17509882

  4. Fluorescent ATP analog mant-ATP reports dynein activity in the isolated Chlamydomonas axoneme

    NASA Astrophysics Data System (ADS)

    Feofilova, Maria; Howard, Jonathon

    Eukaryotic flagella are long rod-like extensions of cells, which play a fundamental role in single cell movement, as well as in fluid transport. Flagella contain a highly evolutionary conserved mechanical structure called the axoneme. The motion of the flagellum is generated by dynein motor proteins located all along the length of the axoneme. How the force production of motors is controlled spatially and temporally is still an open question. Therefore, monitoring dynein activity in the axonemal structure is expected to provide novel insights in regulation of the beat. We use high sensitivity fluorescence microscopy to monitor the binding and hydrolysis kinetics of the fluorescently labeled ATP analogue mant-ATP (2'(3')-O-(N-methylanthraniloyl) adenosine 5'-triphosphate), which is known to support dynein activity. By studying the kinetics of mant-ATP fluorescence, we identified distinct mant-ATP binding sites in the axoneme. The application of this method to axonemes with reduced amounts of dynein, showed evidence that one of the sites is associated with binding to dynein. In the future, we would like to use this method to find the spatial distribution of dynein activity in the axoneme.

  5. DRC2/CCDC65 is a central hub for assembly of the nexin–dynein regulatory complex and other regulators of ciliary and flagellar motility

    PubMed Central

    Bower, Raqual; Tritschler, Douglas; Mills, Kristyn VanderWaal; Heuser, Thomas; Nicastro, Daniela; Porter, Mary E.

    2018-01-01

    The nexin–dynein regulatory complex (N-DRC) plays a central role in the regulation of ciliary and flagellar motility. In most species, the N-DRC contains at least 11 subunits, but the specific function of each subunit is unknown. Mutations in three subunits (DRC1, DRC2/CCDC65, DRC4/GAS8) have been linked to defects in ciliary motility in humans and lead to a ciliopathy known as primary ciliary dyskinesia (PCD). Here we characterize the biochemical, structural, and motility phenotypes of two mutations in the DRC2 gene of Chlamydomonas. Using high-resolution proteomic and structural approaches, we find that the C-terminal region of DRC2 is critical for the coassembly of DRC2 and DRC1 to form the base plate of N-DRC and its attachment to the outer doublet microtubule. Loss of DRC2 in drc2 mutants disrupts the assembly of several other N-DRC subunits and also destabilizes the assembly of several closely associated structures such as the inner dynein arms, the radial spokes, and the calmodulin- and spoke-associated complex. Our study provides new insights into the range of ciliary defects that can lead to PCD. PMID:29167384

  6. Light intermediate chain 1 defines a functional subfraction of cytoplasmic dynein which binds to pericentrin.

    PubMed

    Tynan, S H; Purohit, A; Doxsey, S J; Vallee, R B

    2000-10-20

    The light intermediate chains (LICs) of cytoplasmic dynein consist of multiple isoforms, which undergo post-translational modification to produce a large number of species separable by two-dimensional electrophoresis and which we have proposed to represent at least two gene products. Recently, we demonstrated the first known function for the LICs: binding to the centrosomal protein, pericentrin, which represents a novel, non-dynactin-based cargo-binding mechanism. Here we report the cloning of rat LIC1, which is approximately 75% homologous to rat LIC2 and also contains a P-loop consensus sequence. We compared LIC1 and LIC2 for the ability to interact with pericentrin, and found that only LIC1 will bind. A functional P-loop sequence is not required for this interaction. We have mapped the interaction to the central region of both LIC1 and pericentrin. Using recombinant LICs, we found that they form homooligomers, but not heterooligomers, and exhibit mutually exclusive binding to the heavy chain. Additionally, overexpressed pericentrin is seen to interact with endogenous LIC1 exclusively. Together these results demonstrate the existence of two subclasses of cytoplasmic dynein: LIC1-containing dynein, and LIC2-containing dynein, only the former of which is involved in pericentrin association with dynein.

  7. Discovery of a vezatin-like protein for dynein-mediated early endosome transport

    PubMed Central

    Yao, Xuanli; Arst, Herbert N.; Wang, Xiangfeng; Xiang, Xin

    2015-01-01

    Early endosomes are transported bidirectionally by cytoplasmic dynein and kinesin-3, but how the movements are regulated in vivo remains unclear. Here our forward genetic study led to the discovery of VezA, a vezatin-like protein in Aspergillus nidulans, as a factor critical for early endosome distribution. Loss of vezA causes an abnormal accumulation of early endosomes at the hyphal tip, where microtubule plus ends are located. This abnormal accumulation depends on kinesin-3 and is due to a decrease in the frequency but not the speed of dynein-mediated early endosome movement. VezA-GFP signals are enriched at the hypha tip in an actin-dependent manner but are not obviously associated with early endosomes, thus differing from the early endosome association of the cargo adapter HookA (Hook in A. nidulans). On loss of VezA, HookA associates normally with early endosomes, but the interaction between dynein-dynactin and the early-endosome-bound HookA is significantly decreased. However, VezA is not required for linking dynein-dynactin to the cytosolic ∆C-HookA, lacking the cargo-binding C-terminus. These results identify VezA as a novel regulator required for the interaction between dynein and the Hook-bound early endosomes in vivo. PMID:26378255

  8. A new mode of mitochondrial transport and polarized sorting regulated by Dynein, Milton and Miro.

    PubMed

    Melkov, Anna; Baskar, Raju; Alcalay, Yehonatan; Abdu, Uri

    2016-11-15

    Intrinsic cell microtubule (MT) polarity, together with molecular motors and adaptor proteins, determines mitochondrial polarized targeting and MT-dependent transport. In polarized cells, such as neurons, mitochondrial mobility and transport require the regulation of kinesin and dynein by two adaptor proteins, Milton and Miro. Recently, we found that dynein heavy chain 64C (Dhc64C) is the primary motor protein for both anterograde and retrograde transport of mitochondria in the Drosophila bristle. In this study, we show that a molecular lesion in the Dhc64C allele that reduced bristle mitochondrial velocity generated a variant that acts as a 'slow' dynein in an MT-gliding assay, indicating that dynein directly regulates mitochondrial transport. We also showed that in milton-RNAi flies, mitochondrial flux into the bristle shaft, but not velocity, was significantly reduced. Surprisingly, mitochondria retrograde flux, but not net velocity, was significantly decreased in miro-RNAi flies. We thus reveal a new mode of mitochondrial sorting in polarized cell growth, whereby bi-directional mitochondrial transport undertaken exclusively by dynein is regulated by Milton in the anterograde direction and by a Miro-dependent switch to the retrograde direction. © 2016. Published by The Company of Biologists Ltd.

  9. A microscopy-based screen employing multiplex genome sequencing identifies cargo-specific requirements for dynein velocity

    PubMed Central

    Tan, Kaeling; Roberts, Anthony J.; Chonofsky, Mark; Egan, Martin J.; Reck-Peterson, Samara L.

    2014-01-01

    The timely delivery of membranous organelles and macromolecules to specific locations within the majority of eukaryotic cells depends on microtubule-based transport. Here we describe a screening method to identify mutations that have a critical effect on intracellular transport and its regulation using mutagenesis, multicolor-fluorescence microscopy, and multiplex genome sequencing. This screen exploits the filamentous fungus Aspergillus nidulans, which has many of the advantages of yeast molecular genetics but uses long-range microtubule-based transport in a manner more similar to metazoan cells. Using this method, we identified seven mutants that represent novel alleles of components of the intracellular transport machinery: specifically, kinesin-1, cytoplasmic dynein, and the dynein regulators Lis1 and dynactin. The two dynein mutations identified in our screen map to dynein's AAA+ catalytic core. Single-molecule studies reveal that both mutations reduce dynein's velocity in vitro. In vivo these mutants severely impair the distribution and velocity of endosomes, a known dynein cargo. In contrast, another dynein cargo, the nucleus, is positioned normally in these mutants. These results reveal that different dynein functions have distinct stringencies for motor performance. PMID:24403603

  10. Lis1 Acts as a “Clutch” between the ATPase and Microtubule-Binding Domains of the Dynein Motor

    PubMed Central

    Huang, Julie; Roberts, Anthony J.; Leschziner, Andres E.; Reck-Peterson, Samara L.

    2012-01-01

    Summary The lissencephaly protein Lis1 has been reported to regulate the mechanical behavior of cytoplasmic dynein, the primary minus-end-directed microtubule motor. However, the regulatory mechanism remains poorly understood. Here, we address this issue using purified proteins from Saccharomyces cerevisiae and a combination of techniques, including single-molecule imaging and single-particle electron microscopy. We show that rather than binding to the main ATPase site within dynein's AAA+ ring or its microtubule-binding stalk directly, Lis1 engages the interface between these elements. Lis1 causes individual dynein motors to remain attached to microtubules for extended periods, even during cycles of ATP hydrolysis that would canonically induce detachment. Thus, Lis1 operates like a “clutch” that prevents dynein's ATPase domain from transmitting a detachment signal to its track-binding domain. We discuss how these findings provide a conserved mechanism for dynein functions in living cells that require prolonged microtubule attachments. PMID:22939623

  11. Direct observation shows superposition and large scale flexibility within cytoplasmic dynein motors moving along microtubules

    NASA Astrophysics Data System (ADS)

    Imai, Hiroshi; Shima, Tomohiro; Sutoh, Kazuo; Walker, Matthew L.; Knight, Peter J.; Kon, Takahide; Burgess, Stan A.

    2015-09-01

    Cytoplasmic dynein is a dimeric AAA+ motor protein that performs critical roles in eukaryotic cells by moving along microtubules using ATP. Here using cryo-electron microscopy we directly observe the structure of Dictyostelium discoideum dynein dimers on microtubules at near-physiological ATP concentrations. They display remarkable flexibility at a hinge close to the microtubule binding domain (the stalkhead) producing a wide range of head positions. About half the molecules have the two heads separated from one another, with both leading and trailing motors attached to the microtubule. The other half have the two heads and stalks closely superposed in a front-to-back arrangement of the AAA+ rings, suggesting specific contact between the heads. All stalks point towards the microtubule minus end. Mean stalk angles depend on the separation between their stalkheads, which allows estimation of inter-head tension. These findings provide a structural framework for understanding dynein's directionality and unusual stepping behaviour.

  12. Dynein Clusters into Lipid Microdomains on Phagosomes to Drive Rapid Transport toward Lysosomes.

    PubMed

    Rai, Ashim; Pathak, Divya; Thakur, Shreyasi; Singh, Shampa; Dubey, Alok Kumar; Mallik, Roop

    2016-02-11

    Diverse cellular processes are driven by motor proteins that are recruited to and generate force on lipid membranes. Surprisingly little is known about how membranes control the force from motors and how this may impact specific cellular functions. Here, we show that dynein motors physically cluster into microdomains on the membrane of a phagosome as it matures inside cells. Such geometrical reorganization allows many dyneins within a cluster to generate cooperative force on a single microtubule. This results in rapid directed transport of the phagosome toward microtubule minus ends, likely promoting phagolysosome fusion and pathogen degradation. We show that lipophosphoglycan, the major molecule implicated in immune evasion of Leishmania donovani, inhibits phagosome motion by disrupting the clustering and therefore the cooperative force generation of dynein. These findings appear relevant to several pathogens that prevent phagosome-lysosome fusion by targeting lipid microdomains on phagosomes. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Allograft replacement for absent native tissue.

    PubMed

    Chaudhury, Salma; Wanivenhaus, Florian; Fox, Alice J; Warren, Russell F; Doyle, Maureen; Rodeo, Scott A

    2013-03-01

    Structural instability due to poor soft tissue quality often requires augmentation. Allografts are important biological substitutes that are used for the symptomatic patient in the reconstruction of deficient ligaments, tendons, menisci, and osteochondral defects. Interest in the clinical application of allografts has arisen from the demand to obtain stable anatomy with restoration of function and protection against additional injury, particularly for high-demand patients who participate in sports. Traditionally, allografts were employed to reinforce weakened tissue. However, they can also be employed to substitute deficient or functionally absent tissue, particularly in the sports medicine setting. This article presents a series of 6 cases that utilized allografts to restore functionally deficient anatomic architecture, rather than just simply augmenting the degenerated or damaged native tissue. Detailed discussions are presented of the use of allografts as a successful treatment strategy to replace functionally weakened tissue, often after failed primary repairs.

  14. Allograft Replacement for Absent Native Tissue

    PubMed Central

    Chaudhury, Salma; Wanivenhaus, Florian; Fox, Alice J.; Warren, Russell F.; Doyle, Maureen; Rodeo, Scott A.

    2013-01-01

    Context: Structural instability due to poor soft tissue quality often requires augmentation. Allografts are important biological substitutes that are used for the symptomatic patient in the reconstruction of deficient ligaments, tendons, menisci, and osteochondral defects. Interest in the clinical application of allografts has arisen from the demand to obtain stable anatomy with restoration of function and protection against additional injury, particularly for high-demand patients who participate in sports. Traditionally, allografts were employed to reinforce weakened tissue. However, they can also be employed to substitute deficient or functionally absent tissue, particularly in the sports medicine setting. Objective: This article presents a series of 6 cases that utilized allografts to restore functionally deficient anatomic architecture, rather than just simply augmenting the degenerated or damaged native tissue. Detailed discussions are presented of the use of allografts as a successful treatment strategy to replace functionally weakened tissue, often after failed primary repairs. PMID:24427387

  15. S. pombe CLASP needs dynein, not EB1 or CLIP170, to induce microtubule instability and slows polymerization rates at cell tips in a dynein-dependent manner

    PubMed Central

    Grallert, Agnes; Beuter, Christoph; Craven, Rachel A.; Bagley, Steve; Wilks, Deepti; Fleig, Ursula; Hagan, Iain M.

    2006-01-01

    The Schizosaccharomyces pombe CLIP170-associated protein (CLASP) Peg1 was identified in a screen for mutants with spindle formation defects and a screen for molecules that antagonized EB1 function. The conditional peg1.1 mutant enabled us to identify key features of Peg1 function. First, Peg1 was required to form a spindle and astral microtubules, yet destabilized interphase microtubules. Second, Peg1 was required to slow the polymerization rate of interphase microtubules that establish end-on contact with the cortex at cell tips. Third, Peg1 antagonized the action of S. pombe CLIP170 (Tip1) and EB1 (Mal3). Fourth, although Peg1 resembled higher eukaryotic CLASPs by physically associating with both Mal3 and Tip1, neither Tip1 nor Mal3 was required for Peg1 to destabilize interphase microtubules or for it to associate with microtubules. Conversely, neither Mal3 nor Tip1 required Peg1 to associate with microtubules or cell tips. Consistently, while mal3.Δ and tip1.Δ disrupted linear growth, corrupting peg1 + did not. Fifth, peg1.1 phenotypes resembled those arising from deletion of the single heavy or both light chains of fission yeast dynein. Furthermore, all interphase phenotypes arising from peg1 + manipulation relied on dynein function. Thus, the impact of S. pombe CLASP on interphase microtubule behavior is more closely aligned to dynein than EB1 or CLIP170. PMID:16951255

  16. Stress-Induced CDK5 Activation Disrupts Axonal Transport via Lis1/Ndel1/Dynein.

    PubMed

    Klinman, Eva; Holzbaur, Erika L F

    2015-07-21

    Axonal transport is essential for neuronal function, and defects in transport are associated with multiple neurodegenerative diseases. Aberrant cyclin-dependent kinase 5 (CDK5) activity, driven by the stress-induced activator p25, also is observed in these diseases. Here we show that elevated CDK5 activity increases the frequency of nonprocessive events for a range of organelles, including lysosomes, autophagosomes, mitochondria, and signaling endosomes. Transport disruption induced by aberrant CDK5 activation depends on the Lis1/Ndel1 complex, which directly regulates dynein activity. CDK5 phosphorylation of Ndel1 favors a high affinity Lis1/Ndel/dynein complex that blocks the ATP-dependent release of dynein from microtubules, inhibiting processive motility of dynein-driven cargo. Similar transport defects observed in neurons from a mouse model of amyotrophic lateral sclerosis are rescued by CDK5 inhibition. Together, these studies identify CDK5 as a Lis1/Ndel1-dependent regulator of transport in stressed neurons, and suggest that dysregulated CDK5 activity contributes to the transport deficits observed during neurodegeneration. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Lissencephaly-1 promotes the recruitment of dynein and dynactin to transported mRNAs

    PubMed Central

    Dix, Carly I.; Soundararajan, Harish Chandra; Dzhindzhev, Nikola S.; Begum, Farida; Suter, Beat; Ohkura, Hiroyuki; Stephens, Elaine

    2013-01-01

    Microtubule-based transport mediates the sorting and dispersal of many cellular components and pathogens. However, the mechanisms by which motor complexes are recruited to and regulated on different cargos remain poorly understood. Here we describe a large-scale biochemical screen for novel factors associated with RNA localization signals mediating minus end–directed mRNA transport during Drosophila development. We identified the protein Lissencephaly-1 (Lis1) and found that minus-end travel distances of localizing transcripts are dramatically reduced in lis1 mutant embryos. Surprisingly, given its well-documented role in regulating dynein mechanochemistry, we uncovered an important requirement for Lis1 in promoting the recruitment of dynein and its accessory complex dynactin to RNA localization complexes. Furthermore, we provide evidence that Lis1 levels regulate the overall association of dynein with dynactin. Our data therefore reveal a critical role for Lis1 within the mRNA localization machinery and suggest a model in which Lis1 facilitates motor complex association with cargos by promoting the interaction of dynein with dynactin. PMID:23918939

  18. The role of the dynein light intermediate chain in retrograde IFT and flagellar function in Chlamydomonas

    PubMed Central

    Reck, Jaimee; Schauer, Alexandria M.; VanderWaal Mills, Kristyn; Bower, Raqual; Tritschler, Douglas; Perrone, Catherine A.; Porter, Mary E.

    2016-01-01

    The assembly of cilia and flagella depends on the activity of two microtubule motor complexes, kinesin-2 and dynein-2/1b, but the specific functions of the different subunits are poorly defined. Here we analyze Chlamydomonas strains expressing different amounts of the dynein 1b light intermediate chain (D1bLIC). Disruption of D1bLIC alters the stability of the dynein 1b complex and reduces both the frequency and velocity of retrograde intraflagellar transport (IFT), but it does not eliminate retrograde IFT. Flagellar assembly, motility, gliding, and mating are altered in a dose-dependent manner. iTRAQ-based proteomics identifies a small subset of proteins that are significantly reduced or elevated in d1blic flagella. Transformation with D1bLIC-GFP rescues the mutant phenotypes, and D1bLIC-GFP assembles into the dynein 1b complex at wild-type levels. D1bLIC-GFP is transported with anterograde IFT particles to the flagellar tip, dissociates into smaller particles, and begins processive retrograde IFT in <2 s. These studies demonstrate the role of D1bLIC in facilitating the recycling of IFT subunits and other proteins, identify new components potentially involved in the regulation of IFT, flagellar assembly, and flagellar signaling, and provide insight into the role of D1bLIC and retrograde IFT in other organisms. PMID:27251063

  19. Building Blocks of the Nexin-Dynein Regulatory Complex in Chlamydomonas Flagella*

    PubMed Central

    Lin, Jianfeng; Tritschler, Douglas; Song, Kangkang; Barber, Cynthia F.; Cobb, Jennifer S.; Porter, Mary E.; Nicastro, Daniela

    2011-01-01

    The directional flow generated by motile cilia and flagella is critical for many processes, including human development and organ function. Normal beating requires the control and coordination of thousands of dynein motors, and the nexin-dynein regulatory complex (N-DRC) has been identified as an important regulatory node for orchestrating dynein activity. The nexin link appears to be critical for the transformation of dynein-driven, linear microtubule sliding to flagellar bending, yet the molecular composition and mechanism of the N-DRC remain largely unknown. Here, we used proteomics with special attention to protein phosphorylation to analyze the composition of the N-DRC and to determine which subunits may be important for signal transduction. Two-dimensional electrophoresis and MALDI-TOF mass spectrometry of WT and mutant flagellar axonemes from Chlamydomonas identified 12 N-DRC-associated proteins, including all seven previously observed N-DRC components. Sequence and PCR analyses identified the mutation responsible for the phenotype of the sup-pf-4 strain, and biochemical comparison with a radial spoke mutant revealed two components that may link the N-DRC and the radial spokes. Phosphoproteomics revealed eight proteins with phosphorylated isoforms for which the isoform patterns changed with the genotype as well as two components that may play pivotal roles in N-DRC function through their phosphorylation status. These data were assembled into a model of the N-DRC that explains aspects of its regulatory function. PMID:21700706

  20. Dynein Separately Partners with NDE1 and Dynactin To Orchestrate T Cell Focused Secretion.

    PubMed

    Nath, Shubhankar; Christian, Laura; Tan, Sarah Youngsun; Ki, Sanghee; Ehrlich, Lauren I R; Poenie, Martin

    2016-09-15

    Helper and cytotoxic T cells accomplish focused secretion through the movement of vesicles toward the microtubule organizing center (MTOC) and translocation of the MTOC to the target contact site. In this study, using Jurkat cells and OT-I TCR transgenic primary murine CTLs, we show that the dynein-binding proteins nuclear distribution E homolog 1 (NDE1) and dynactin (as represented by p150(Glued)) form mutually exclusive complexes with dynein, exhibit nonoverlapping distributions in target-stimulated cells, and mediate different transport events. When Jurkat cells expressing a dominant negative form of NDE1 (NDE1-enhanced GFP fusion) were activated by Staphylococcus enterotoxin E-coated Raji cells, NDE1 and dynein failed to accumulate at the immunological synapse (IS) and MTOC translocation was inhibited. Knockdown of NDE1 in Jurkat cells or primary mouse CTLs also inhibited MTOC translocation and CTL-mediated killing. In contrast to NDE1, knockdown of p150(Glued), which depleted the alternative dynein/dynactin complex, resulted in impaired accumulation of CTLA4 and granzyme B-containing intracellular vesicles at the IS, whereas MTOC translocation was not affected. Depletion of p150(Glued) in CTLs also inhibited CTL-mediated lysis. We conclude that the NDE1/Lissencephaly 1 and dynactin complexes separately mediate two key components of T cell-focused secretion, namely translocation of the MTOC and lytic granules to the IS, respectively. Copyright © 2016 by The American Association of Immunologists, Inc.

  1. Steady dynein forces induce flutter instability and propagating waves in mathematical models of flagella

    PubMed Central

    Dutcher, S. K.

    2016-01-01

    Cilia and flagella are highly conserved organelles that beat rhythmically with propulsive, oscillatory waveforms. The mechanism that produces these autonomous oscillations remains a mystery. It is widely believed that dynein activity must be dynamically regulated (switched on and off, or modulated) on opposite sides of the axoneme to produce oscillations. A variety of regulation mechanisms have been proposed based on feedback from mechanical deformation to dynein force. In this paper, we show that a much simpler interaction between dynein and the passive components of the axoneme can produce coordinated, propulsive oscillations. Steady, distributed axial forces, acting in opposite directions on coupled beams in viscous fluid, lead to dynamic structural instability and oscillatory, wave-like motion. This ‘flutter’ instability is a dynamic analogue to the well-known static instability, buckling. Flutter also occurs in slender beams subjected to tangential axial loads, in aircraft wings exposed to steady air flow and in flexible pipes conveying fluid. By analysis of the flagellar equations of motion and simulation of structural models of flagella, we demonstrate that dynein does not need to switch direction or inactivate to produce autonomous, propulsive oscillations, but must simply pull steadily above a critical threshold force. PMID:27798276

  2. Engineered tug-of-war between kinesin and dynein controls direction of microtubule transport in vivo

    PubMed Central

    Rezaul, Karim; Gupta, Dipika; Semenova, Irina; Ikeda, Kazuho; Kraikivski, Pavel; Yu, Ji; Cowan, Ann; Zaliapin, Ilya; Rodionov, Vladimir

    2017-01-01

    Bidirectional transport of membrane organelles along microtubules (MTs) is driven by plus-end directed kinesins and minus-end directed dynein bound to the same cargo. Activities of opposing MT motors produce bidirectional movement of membrane organelles and cytoplasmic particles along MT transport tracks. Directionality of MT-based transport might be controlled by a protein complex that determines which motor type is active at any given moment of time, or determined by the outcome of a tug-of-war between MT motors dragging cargo organelles in opposite directions. However, evidence in support of each mechanisms of regulation is based mostly on the results of theoretical analyses or indirect experimental data. Here, we test whether the direction of movement of membrane organelles in vivo can be controlled by the tug-of-war between opposing MT motors alone, by attaching large number of kinesin-1 motors to organelles transported by dynein to minus-ends of MTs. We find that recruitment of kinesin significantly reduces the length and velocity of minus-end-directed dynein-dependent MT runs, leading to a reversal of the overall direction of dynein-driven organelles in vivo. Therefore in the absence of external regulators tug-of-war between opposing MT motors alone is sufficient to determine the directionality of MT transport in vivo. PMID:26843027

  3. Angular measurements of the dynein ring reveal a stepping mechanism dependent on a flexible stalk

    PubMed Central

    Lippert, Lisa G.; Dadosh, Tali; Hadden, Jodi A.; Karnawat, Vishakha; Diroll, Benjamin T.; Murray, Christopher B.; Holzbaur, Erika L. F.; Schulten, Klaus; Reck-Peterson, Samara L.; Goldman, Yale E.

    2017-01-01

    The force-generating mechanism of dynein differs from the force-generating mechanisms of other cytoskeletal motors. To examine the structural dynamics of dynein’s stepping mechanism in real time, we used polarized total internal reflection fluorescence microscopy with nanometer accuracy localization to track the orientation and position of single motors. By measuring the polarized emission of individual quantum nanorods coupled to the dynein ring, we determined the angular position of the ring and found that it rotates relative to the microtubule (MT) while walking. Surprisingly, the observed rotations were small, averaging only 8.3°, and were only weakly correlated with steps. Measurements at two independent labeling positions on opposite sides of the ring showed similar small rotations. Our results are inconsistent with a classic power-stroke mechanism, and instead support a flexible stalk model in which interhead strain rotates the rings through bending and hinging of the stalk. Mechanical compliances of the stalk and hinge determined based on a 3.3-μs molecular dynamics simulation account for the degree of ring rotation observed experimentally. Together, these observations demonstrate that the stepping mechanism of dynein is fundamentally different from the stepping mechanisms of other well-studied MT motors, because it is characterized by constant small-scale fluctuations of a large but flexible structure fully consistent with the variable stepping pattern observed as dynein moves along the MT. PMID:28533393

  4. Axonal autophagosomes recruit dynein for retrograde transport through fusion with late endosomes

    PubMed Central

    Cheng, Xiu-Tang; Zhou, Bing; Lin, Mei-Yao; Cai, Qian

    2015-01-01

    Efficient degradation of autophagic vacuoles (AVs) via lysosomes is an important cellular homeostatic process. This is particularly challenging for neurons because mature acidic lysosomes are relatively enriched in the soma. Although dynein-driven retrograde transport of AVs was suggested, a fundamental question remains how autophagosomes generated at distal axons acquire dynein motors for retrograde transport toward the soma. In this paper, we demonstrate that late endosome (LE)–loaded dynein–snapin complexes drive AV retrograde transport in axons upon fusion of autophagosomes with LEs into amphisomes. Blocking the fusion with syntaxin17 knockdown reduced recruitment of dynein motors to AVs, thus immobilizing them in axons. Deficiency in dynein–snapin coupling impaired AV transport, resulting in AV accumulation in neurites and synaptic terminals. Altogether, our study provides the first evidence that autophagosomes recruit dynein through fusion with LEs and reveals a new motor–adaptor sharing mechanism by which neurons may remove distal AVs engulfing aggregated proteins and dysfunctional organelles for efficient degradation in the soma. PMID:25940348

  5. WD60/FAP163 is a dynein intermediate chain required for retrograde intraflagellar transport in cilia

    PubMed Central

    Patel-King, Ramila S.; Gilberti, Renée M.; Hom, Erik F. Y.; King, Stephen M.

    2013-01-01

    Retrograde intraflagellar transport (IFT) is required for assembly of cilia. We identify a Chlamydomonas flagellar protein (flagellar-associated protein 163 [FAP163]) as being closely related to the D1bIC(FAP133) intermediate chain (IC) of the dynein that powers this movement. Biochemical analysis revealed that FAP163 is present in the flagellar matrix and is actively trafficked by IFT. Furthermore, FAP163 copurified with D1bIC(FAP133) and the LC8 dynein light chain, indicating that it is an integral component of the retrograde IFT dynein. To assess the functional role of FAP163, we generated an RNA interference knockdown of the orthologous protein (WD60) in planaria. The Smed-wd60(RNAi) animals had a severe ciliary assembly defect that dramatically compromised whole-organism motility. Most cilia were present as short stubs that had accumulated large quantities of IFT particle–like material between the doublet microtubules and the membrane. The few remaining approximately full-length cilia had a chaotic beat with a frequency reduced from 24 to ∼10 Hz. Thus WD60/FAP163 is a dynein IC that is absolutely required for retrograde IFT and ciliary assembly. PMID:23864713

  6. Alcohol-induced defects in hepatic transcytosis may be explained by impaired dynein function.

    PubMed

    Groebner, Jennifer L; Fernandez, David J; Tuma, Dean J; Tuma, Pamela L

    2014-12-01

    Alcoholic liver disease has been clinically well described, but the molecular mechanisms leading to hepatotoxicity have not been fully elucidated. Previously, we determined that microtubules are hyperacetylated and more stable in ethanol-treated WIF-B cells, VL-17A cells, liver slices, and in livers from ethanol-fed rats. From our recent studies, we believe that these modifications can explain alcohol-induced defects in microtubule motor-dependent protein trafficking including nuclear translocation of a subset of transcription factors. Since cytoplasmic dynein/dynactin is known to mediate both microtubule-dependent translocation and basolateral to apical/canalicular transcytosis, we predicted that transcytosis is impaired in ethanol-treated hepatic cells. We monitored transcytosis of three classes of newly synthesized canalicular proteins in polarized, hepatic WIF-B cells, an emerging model system for the study of liver disease. As predicted, canalicular delivery of all proteins tested was impaired in ethanol-treated cells. Unlike in control cells, transcytosing proteins were observed in discrete sub-canalicular puncta en route to the canalicular surface that aligned along acetylated microtubules. We further determined that the stalled transcytosing proteins colocalized with dynein/dynactin in treated cells. No changes in vesicle association were observed for either dynein or dynactin in ethanol-treated cells, but significantly enhanced dynein binding to microtubules was observed. From these results, we propose that enhanced dynein binding to microtubules in ethanol-treated cells leads to decreased motor processivity resulting in vesicle stalling and in impaired canalicular delivery. Our studies also importantly indicate that modulating cellular acetylation levels with clinically tolerated deacetylase agonists may be a novel therapeutic strategy for treating alcoholic liver disease.

  7. Alcohol-induced defects in hepatic transcytosis may be explained by impaired dynein function

    PubMed Central

    Groebner, Jennifer L.; Fernandez, David J.; Tuma, Dean J.; Tuma, Pamela L.

    2016-01-01

    Alcoholic liver disease has been clinically well described, but the molecular mechanisms leading to hepatotoxicity have not been fully elucidated. Previously, we determined that microtubules are hyperacetylated and more stable in ethanol-treated WIF-B cells, VL-17A cells, liver slices, and in livers from ethanol-fed rats. From our recent studies, we believe that these modifications can explain alcohol-induced defects in microtubule motor-dependent protein trafficking including nuclear translocation of a subset of transcription factors. Since cytoplasmic dynein/dynactin is known to mediate both microtubule-dependent translocation and basolateral to apical/canalicular transcytosis, we predicted that transcytosis is impaired in ethanol-treated hepatic cells. We monitored transcytosis of three classes of newly synthesized canalicular proteins in polarized, hepatic WIF-B cells, an emerging model system for the study of liver disease. As predicted, canalicular delivery of all proteins tested was impaired in ethanol-treated cells. Unlike in control cells, transcytosing proteins were observed in discrete sub-canalicular puncta en route to the canalicular surface that aligned along acetylated microtubules. We further determined that the stalled transcytosing proteins colocalized with dynein/dynactin in treated cells. No changes in vesicle association were observed for either dynein or dynactin in ethanol-treated cells, but significantly enhanced dynein binding to micro-tubules was observed. From these results, we propose that enhanced dynein binding to microtubules in ethanol-treated cells leads to decreased motor processivity resulting in vesicle stalling and in impaired canalicular delivery. Our studies also importantly indicate that modulating cellular acetylation levels with clinically tolerated deacetylase agonists may be a novel therapeutic strategy for treating alcoholic liver disease. PMID:25148871

  8. Cytoplasmic dynein undergoes intracellular redistribution concomitant with phosphorylation of the heavy chain in response to serum starvation and okadaic acid.

    PubMed

    Lin, S X; Ferro, K L; Collins, C A

    1994-11-01

    Cytoplasmic dynein is a microtubule-binding protein which is considered to serve as a motor for retrograde organelle movement. In cultured fibroblasts, cytoplasmic dynein localizes primarily to lysosomes, membranous organelles whose movement and distribution in the cytoplasm have been shown to be dependent on the integrity of the microtubule cytoskeleton. We have recently identified conditions which lead to an apparent dissociation of dynein from lysosomes in vivo, indicating that alterations in membrane binding may be involved in the regulation of retrograde organelle movement (Lin, S. X. H., and C. A. Collins. 1993. J. Cell Sci. 105:579-588). Both brief serum withdrawal and low extracellular calcium levels induced this alteration, and the effect was reversed upon addition of serum or additional calcium. Here we demonstrate that the phosphorylation state of the dynein molecule is correlated with changes in its intracellular distribution in normal rat kidney fibroblasts. Dynein heavy chain phosphorylation level increased during serum starvation, and decreased back to control levels upon subsequent addition of serum. We found that okadaic acid, a phosphoprotein phosphatase inhibitor, mimicked the effects of serum starvation on both phosphorylation and the intracellular redistribution of dynein from a membrane-associated pool to one that was more soluble, with similar dose dependence for both phenomena. Cell fractionation by differential detergent extraction revealed that a higher proportion of dynein was present in a soluble pool after serum starvation than was found in comparable fractions from control cells. Our data indicate that cytoplasmic dynein is phosphorylated in vivo, and changes in phosphorylation state may be involved in a regulatory mechanism affecting the distribution of this protein among intracellular compartments.

  9. Zwint-1 is a novel Aurora B substrate required for the assembly of a dynein-binding platform on kinetochores

    PubMed Central

    Kasuboski, James M.; Bader, Jason R.; Vaughan, Patricia S.; Tauhata, Sinji B. F.; Winding, Michael; Morrissey, Meghan A.; Joyce, Michelle V.; Boggess, William; Vos, Larissa; Chan, Gordon K.; Hinchcliffe, Edward H.; Vaughan, Kevin T.

    2011-01-01

    Aurora B (AurB) is a mitotic kinase responsible for multiple aspects of mitotic progression, including assembly of the outer kinetochore. Cytoplasmic dynein is an abundant kinetochore protein whose recruitment to kinetochores requires phosphorylation. To assess whether AurB regulates recruitment of dynein to kinetochores, we inhibited AurB using ZM447439 or a kinase-dead AurB construct. Inhibition of AurB reduced accumulation of dynein at kinetochores substantially; however, this reflected a loss of dynein-associated proteins rather than a defect in dynein phosphorylation. We determined that AurB inhibition affected recruitment of the ROD, ZW10, zwilch (RZZ) complex to kinetochores but not zwint-1 or more-proximal kinetochore proteins. AurB phosphorylated zwint-1 but not ZW10 in vitro, and three novel phosphorylation sites were identified by tandem mass spectrometry analysis. Expression of a triple-Ala zwint-1 mutant blocked kinetochore assembly of RZZ-dependent proteins and induced defects in chromosome movement during prometaphase. Expression of a triple-Glu zwint-1 mutant rendered cells resistant to AurB inhibition during prometaphase. However, cells expressing the triple-Glu mutant failed to satisfy the spindle assembly checkpoint (SAC) at metaphase because poleward streaming of dynein/dynactin/RZZ was inhibited. These studies identify zwint-1 as a novel AurB substrate required for kinetochore assembly and for proper SAC silencing at metaphase. PMID:21775627

  10. Accumulation of Cytoplasmic Dynein and Dynactin at Microtubule Plus Ends in Aspergillus nidulans Is Kinesin DependentV⃞

    PubMed Central

    Zhang, Jun; Li, Shihe; Fischer, Reinhard; Xiang, Xin

    2003-01-01

    The mechanism(s) by which microtubule plus-end tracking proteins are targeted is unknown. In the filamentous fungus Aspergillus nidulans, both cytoplasmic dynein and NUDF, the homolog of the LIS1 protein, localize to microtubule plus ends as comet-like structures. Herein, we show that NUDM, the p150 subunit of dynactin, also forms dynamic comet-like structures at microtubule plus ends. By examining proteins tagged with green fluorescent protein in different loss-of-function mutants, we demonstrate that dynactin and cytoplasmic dynein require each other for microtubule plus-end accumulation, and the presence of cytoplasmic dynein is also important for NUDF's plus-end accumulation. Interestingly, deletion of NUDF increases the overall accumulation of dynein and dynactin at plus ends, suggesting that NUDF may facilitate minus-end–directed dynein movement. Finally, we demonstrate that a conventional kinesin, KINA, is required for the microtubule plus-end accumulation of cytoplasmic dynein and dynactin, but not of NUDF. PMID:12686603

  11. Cdk1 Activates Pre-mitotic Nuclear Envelope Dynein Recruitment and Apical Nuclear Migration in Neural Stem Cells.

    PubMed

    Baffet, Alexandre D; Hu, Daniel J; Vallee, Richard B

    2015-06-22

    Dynein recruitment to the nuclear envelope is required for pre-mitotic nucleus-centrosome interactions in nonneuronal cells and for apical nuclear migration in neural stem cells. In each case, dynein is recruited to the nuclear envelope (NE) specifically during G2 via two nuclear pore-mediated mechanisms involving RanBP2-BicD2 and Nup133-CENP-F. The mechanisms responsible for cell-cycle control of this behavior are unknown. We now find that Cdk1 serves as a direct master controller for NE dynein recruitment in neural stem cells and HeLa cells. Cdk1 phosphorylates conserved sites within RanBP2 and activates BicD2 binding and early dynein recruitment. Late recruitment is triggered by a Cdk1-induced export of CENP-F from the nucleus. Forced NE targeting of BicD2 overrides Cdk1 inhibition, fully rescuing dynein recruitment and nuclear migration in neural stem cells. These results reveal how NE dynein recruitment is cell-cycle regulated and identify the trigger mechanism for apical nuclear migration in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Robotic arm

    DOEpatents

    Kwech, Horst

    1989-04-18

    A robotic arm positionable within a nuclear vessel by access through a small diameter opening and having a mounting tube supported within the vessel and mounting a plurality of arm sections for movement lengthwise of the mounting tube as well as for movement out of a window provided in the wall of the mounting tube. An end effector, such as a grinding head or welding element, at an operating end of the robotic arm, can be located and operated within the nuclear vessel through movement derived from six different axes of motion provided by mounting and drive connections between arm sections of the robotic arm. The movements are achieved by operation of remotely-controllable servo motors, all of which are mounted at a control end of the robotic arm to be outside the nuclear vessel.

  13. Asymmetries in kinesin-2 and cytoplasmic dynein contributions to melanosome transport.

    PubMed

    De Rossi, María Cecilia; De Rossi, María Emilia; Sued, Mariela; Rodríguez, Daniela; Bruno, Luciana; Levi, Valeria

    2015-09-14

    The mechanisms involved in bidirectional transport along microtubules remain largely unknown. We explored the collective action of kinesin-2 and dynein motors during transport of melanosomes in Xenopus laevis melanophores. These motors are attached to organelles through accessory proteins establishing a complex molecular linker. We determined both the stiffness of this linker and the organelles speed and observed that these parameters depended on the organelle size and cargo direction. Our results suggest that melanosome transport is driven by two dissimilar teams: whereas dynein motors compete with kinesin-2 affecting the properties of plus-end directed organelles, kinesin-2 does not seem to play a similar role during minus-end transport. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  14. Evolution of the eukaryotic dynactin complex, the activator of cytoplasmic dynein

    PubMed Central

    2012-01-01

    Background Dynactin is a large multisubunit protein complex that enhances the processivity of cytoplasmic dynein and acts as an adapter between dynein and the cargo. It is composed of eleven different polypeptides of which eight are unique to this complex, namely dynactin1 (p150Glued), dynactin2 (p50 or dynamitin), dynactin3 (p24), dynactin4 (p62), dynactin5 (p25), dynactin6 (p27), and the actin-related proteins Arp1 and Arp10 (Arp11). Results To reveal the evolution of dynactin across the eukaryotic tree the presence or absence of all dynactin subunits was determined in most of the available eukaryotic genome assemblies. Altogether, 3061 dynactin sequences from 478 organisms have been annotated. Phylogenetic trees of the various subunit sequences were used to reveal sub-family relationships and to reconstruct gene duplication events. Especially in the metazoan lineage, several of the dynactin subunits were duplicated independently in different branches. The largest subunit repertoire is found in vertebrates. Dynactin diversity in vertebrates is further increased by alternative splicing of several subunits. The most prominent example is the dynactin1 gene, which may code for up to 36 different isoforms due to three different transcription start sites and four exons that are spliced as differentially included exons. Conclusions The dynactin complex is a very ancient complex that most likely included all subunits in the last common ancestor of extant eukaryotes. The absence of dynactin in certain species coincides with that of the cytoplasmic dynein heavy chain: Organisms that do not encode cytoplasmic dynein like plants and diplomonads also do not encode the unique dynactin subunits. The conserved core of dynactin consists of dynactin1, dynactin2, dynactin4, dynactin5, Arp1, and the heterodimeric actin capping protein. The evolution of the remaining subunits dynactin3, dynactin6, and Arp10 is characterized by many branch- and species-specific gene loss events. PMID

  15. RNA-directed activation of cytoplasmic dynein-1 in reconstituted transport RNPs.

    PubMed

    McClintock, Mark A; Dix, Carly I; Johnson, Christopher M; McLaughlin, Stephen H; Maizels, Rory J; Hoang, Ha Thi; Bullock, Simon L

    2018-06-26

    Polarised mRNA transport is a prevalent mechanism for spatial control of protein synthesis. However, the composition of transported ribonucleoprotein particles (RNPs) and the regulation of their movement are poorly understood. We have reconstituted microtubule minus end-directed transport of mRNAs using purified components. A Bicaudal-D (BicD) adaptor protein and the RNA-binding protein Egalitarian (Egl) are sufficient for long-distance mRNA transport by the dynein motor and its accessory complex dynactin, thus defining a minimal transport-competent RNP. Unexpectedly, the RNA is required for robust activation of dynein motility. We show that a cis -acting RNA localisation signal promotes the interaction of Egl with BicD, which licenses the latter protein to recruit dynein and dynactin. Our data support a model for BicD activation based on RNA-induced occupancy of two Egl-binding sites on the BicD dimer. Scaffolding of adaptor protein assemblies by cargoes is an attractive mechanism for regulating intracellular transport. © 2018, McClintock et al.

  16. Dynein pulling forces counteract lamin-mediated nuclear stability during nuclear envelope repair

    PubMed Central

    Penfield, Lauren; Wysolmerski, Brian; Mauro, Michael; Farhadifar, Reza; Martinez, Michael A.; Biggs, Ronald; Wu, Hai-Yin; Broberg, Curtis; Needleman, Daniel; Bahmanyar, Shirin

    2018-01-01

    Recent work done exclusively in tissue culture cells revealed that the nuclear envelope (NE) ruptures and repairs in interphase. The duration of NE ruptures depends on lamins; however, the underlying mechanisms and relevance to in vivo events are not known. Here, we use the Caenorhabditis elegans zygote to analyze lamin’s role in NE rupture and repair in vivo. Transient NE ruptures and subsequent NE collapse are induced by weaknesses in the nuclear lamina caused by expression of an engineered hypomorphic C. elegans lamin allele. Dynein-generated forces that position nuclei enhance the severity of transient NE ruptures and cause NE collapse. Reduction of dynein forces allows the weakened lamin network to restrict nucleo–cytoplasmic mixing and support stable NE recovery. Surprisingly, the high incidence of transient NE ruptures does not contribute to embryonic lethality, which is instead correlated with stochastic chromosome scattering resulting from premature NE collapse, suggesting that C. elegans tolerates transient losses of NE compartmentalization during early embryogenesis. In sum, we demonstrate that lamin counteracts dynein forces to promote stable NE repair and prevent catastrophic NE collapse, and thus provide the first mechanistic analysis of NE rupture and repair in an organismal context. PMID:29386297

  17. Microtubule minus end motors kinesin-14 and dynein drive nuclear congression in parallel pathways

    PubMed Central

    Scheffler, Kathleen; Minnes, Refael; Fraisier, Vincent; Paoletti, Anne

    2015-01-01

    Microtubules (MTs) and associated motors play a central role in nuclear migration, which is crucial for diverse biological functions including cell division, polarity, and sexual reproduction. In this paper, we report a dual mechanism underlying nuclear congression during fission yeast karyogamy upon mating of haploid cells. Using microfluidic chambers for long-term imaging, we captured the precise timing of nuclear congression and identified two minus end–directed motors operating in parallel in this process. Kinesin-14 Klp2 associated with MTs may cross-link and slide antiparallel MTs emanating from the two nuclei, whereas dynein accumulating at spindle pole bodies (SPBs) may pull MTs nucleated from the opposite SPB. Klp2-dependent nuclear congression proceeds at constant speed, whereas dynein accumulation results in an increase of nuclear velocity over time. Surprisingly, the light intermediate chain Dli1, but not dynactin, is required for this previously unknown function of dynein. We conclude that efficient nuclear congression depends on the cooperation of two minus end–directed motors. PMID:25869666

  18. Microtubule minus end motors kinesin-14 and dynein drive nuclear congression in parallel pathways.

    PubMed

    Scheffler, Kathleen; Minnes, Refael; Fraisier, Vincent; Paoletti, Anne; Tran, Phong T

    2015-04-13

    Microtubules (MTs) and associated motors play a central role in nuclear migration, which is crucial for diverse biological functions including cell division, polarity, and sexual reproduction. In this paper, we report a dual mechanism underlying nuclear congression during fission yeast karyogamy upon mating of haploid cells. Using microfluidic chambers for long-term imaging, we captured the precise timing of nuclear congression and identified two minus end-directed motors operating in parallel in this process. Kinesin-14 Klp2 associated with MTs may cross-link and slide antiparallel MTs emanating from the two nuclei, whereas dynein accumulating at spindle pole bodies (SPBs) may pull MTs nucleated from the opposite SPB. Klp2-dependent nuclear congression proceeds at constant speed, whereas dynein accumulation results in an increase of nuclear velocity over time. Surprisingly, the light intermediate chain Dli1, but not dynactin, is required for this previously unknown function of dynein. We conclude that efficient nuclear congression depends on the cooperation of two minus end-directed motors. © 2015 Scheffler et al.

  19. Regulation of dynein-mediated autophagosomes trafficking by ASM in CASMCs.

    PubMed

    Xu, Ming; Zhang, Qiufang; Li, Pin-Lan; Nguyen, Thaison; Li, Xiang; Zhang, Yang

    2016-01-01

    Acid sphingomyelinase (ASM; gene symbol Smpd1) has been shown to play a crucial role in autophagy maturation by controlling lysosomal fusion with autophagosomes in coronary arterial smooth muscle cells (CASMCs). However, the underlying molecular mechanism by which ASM controls autophagolysosomal fusion remains unknown. In primary cultured CASMCs, lysosomal Ca2+ induced by 7-ketocholesterol (7-Ket, an atherogenic stimulus and autophagy inducer) was markedly attenuated by ASM deficiency or TRPML1 gene silencing suggesting that ASM signaling is required for TRPML1 channel activity and subsequent lysosomal Ca(2+) release. In these CASMCs, ASM deficiency or TRPML1 gene silencing markedly inhibited 7-Ket-induced dynein activation. In addition, 7-Ket-induced autophagosome trafficking, an event associated with lysosomal Ca(2+) release and dynein activity, was significantly inhibited in ASM-deficient (Smpd1(-/-)) CASMCs compared to that in Smpd1(+/+) CASMCs. Finally, overexpression of TRPML1 proteins restored 7-Ket-induced lysosomal Ca(2+) release and autophagosome trafficking in Smpd1-/- CASMCs. Collectively, these results suggest that ASM plays a critical role in regulating lysosomal TRPML1-Ca(2+) signaling and subsequent dynein-mediated autophagosome trafficking, which leads its role in controlling autophagy maturation in CASMCs under atherogenic stimulation.

  20. 46 CFR 502.243 - Participation of absent Commissioner.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... AND PROCEDURE Oral Argument; Submission for Final Decision § 502.243 Participation of absent... participate in a decision shall participate in making that decision after reading the transcript of oral... 46 Shipping 9 2010-10-01 2010-10-01 false Participation of absent Commissioner. 502.243 Section...

  1. Communication about absent entities in great apes and human infants.

    PubMed

    Bohn, Manuel; Call, Josep; Tomasello, Michael

    2015-12-01

    There is currently debate about the extent to which non-linguistic beings such as human infants and great apes are capable of absent reference. In a series of experiments we investigated the flexibility and specificity of great apes' (N=36) and 12 month-old infants' (N=40) requests for absent entities. Subjects had the choice between requesting visible objects directly and using the former location of a depleted option to request more of these now-absent entities. Importantly, we systematically varied the quality of the present and absent options. We found that great apes as well as human infants flexibly adjusted their requests for absent entities to these contextual variations and only requested absent entities when the visible option was of lower quality than the absent option. These results suggest that the most basic cognitive capacities for absent reference do not depend on language and are shared by humans and their closest living relatives. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Lis1 acts as a "clutch" between the ATPase and microtubule-binding domains of the dynein motor.

    PubMed

    Huang, Julie; Roberts, Anthony J; Leschziner, Andres E; Reck-Peterson, Samara L

    2012-08-31

    The lissencephaly protein Lis1 has been reported to regulate the mechanical behavior of cytoplasmic dynein, the primary minus-end-directed microtubule motor. However, the regulatory mechanism remains poorly understood. Here, we address this issue using purified proteins from Saccharomyces cerevisiae and a combination of techniques, including single-molecule imaging and single-particle electron microscopy. We show that rather than binding to the main ATPase site within dynein's AAA+ ring or its microtubule-binding stalk directly, Lis1 engages the interface between these elements. Lis1 causes individual dynein motors to remain attached to microtubules for extended periods, even during cycles of ATP hydrolysis that would canonically induce detachment. Thus, Lis1 operates like a "clutch" that prevents dynein's ATPase domain from transmitting a detachment signal to its track-binding domain. We discuss how these findings provide a conserved mechanism for dynein functions in living cells that require prolonged microtubule attachments. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Computer simulation of flagellar movement VIII: coordination of dynein by local curvature control can generate helical bending waves.

    PubMed

    Brokaw, Charles J

    2002-10-01

    Computer simulations have been carried out with a model flagellum that can bend in three dimensions. A pattern of dynein activation in which regions of dynein activity propagate along each doublet, with a phase shift of approximately 1/9 wavelength between adjacent doublets, will produce a helical bending wave. This pattern can be termed "doublet metachronism." The simulations show that doublet metachronism can arise spontaneously in a model axoneme in which activation of dyneins is controlled locally by the curvature of each outer doublet microtubule. In this model, dyneins operate both as sensors of curvature and as motors. Doublet metachronism and the chirality of the resulting helical bending pattern are regulated by the angular difference between the direction of the moment and sliding produced by dyneins on a doublet and the direction of the controlling curvature for that doublet. A flagellum that is generating a helical bending wave experiences twisting moments when it moves against external viscous resistance. At high viscosities, helical bending will be significantly modified by twist unless the twist resistance is greater than previously estimated. Spontaneous doublet metachronism must be modified or overridden in order for a flagellum to generate the planar bending waves that are required for efficient propulsion of spermatozoa. Planar bending can be achieved with the three-dimensional flagellar model by appropriate specification of the direction of the controlling curvature for each doublet. However, experimental observations indicate that this "hard-wired" solution is not appropriate for real flagella. Copyright 2002 Wiley-Liss, Inc.

  4. Dynein-ADP as a force-generating intermediate revealed by a rapid reactivation of flagellar axoneme.

    PubMed Central

    Tani, T; Kamimura, S

    1999-01-01

    Fragmented flagellar axonemes of sand dollar spermatozoa were reactivated by rapid photolysis of caged ATP. After a time lag of 10 ms, axonemes treated with protease started sliding disintegration. Axonemes without protease digestion started nanometer-scale high-frequency oscillation after a similar time lag. Force development in the sliding disintegration was measured with a flexible glass needle and its time course was corresponded well to that of the dynein-ADP intermediate production estimated using kinetic rates previously reported. However, with a high concentration ( approximately 80 microM) of vanadate, which binds to the dynein-ADP intermediate and forms a stable complex of dynein-ADP-vanadate, the time course of force development in sliding disintegration was not affected at all. In the case of high frequency oscillation, the time lag to start the oscillation, the initial amplitude, and the initial frequency were not affected by vanadate, though the oscillation once started was damped more quickly at higher concentrations of vanadate. These results suggest that during the initial turnover of ATP hydrolysis, force generation of dynein is not blocked by vanadate. A vanadate-insensitive dynein-ADP is postulated as a force-generating intermediate. PMID:10465762

  5. Clustering of nuclei in multinucleated hyphae is prevented by dynein-driven bidirectional nuclear movements and microtubule growth control in Ashbya gossypii.

    PubMed

    Grava, Sandrine; Keller, Miyako; Voegeli, Sylvia; Seger, Shanon; Lang, Claudia; Philippsen, Peter

    2011-07-01

    During filamentous fungus development, multinucleated hyphae employ a system for long-range nuclear migration to maintain an equal nuclear density. A decade ago the microtubule motor dynein was shown to play a central role in this process. Previous studies with Ashbya gossypii revealed extensive bidirectional movements and bypassings of nuclei, an autonomous cytoplasmic microtubule (cMT) cytoskeleton emanating from each nucleus, and pulling of nuclei by sliding of cMTs along the cortex. Here, we show that dynein is the sole motor for bidirectional movements and bypassing because these movements are concomitantly decreased in mutants carrying truncations of the dynein heavy-chain DYN1 promoter. The dynactin component Jnm1, the accessory proteins Dyn2 and Ndl1, and the potential dynein cortical anchor Num1 are also involved in the dynamic distribution of nuclei. In their absence, nuclei aggregate to different degrees, whereby the mutants with dense nuclear clusters grow extremely long cMTs. As in budding yeast, we found that dynein is delivered to cMT plus ends, and its activity or processivity is probably controlled by dynactin and Num1. Together with its role in powering nuclear movements, we propose that dynein also plays (directly or indirectly) a role in the control of cMT length. Those combined dynein actions prevent nuclear clustering in A. gossypii and thus reveal a novel cellular role for dynein.

  6. Clustering of Nuclei in Multinucleated Hyphae Is Prevented by Dynein-Driven Bidirectional Nuclear Movements and Microtubule Growth Control in Ashbya gossypii ▿ †

    PubMed Central

    Grava, Sandrine; Keller, Miyako; Voegeli, Sylvia; Seger, Shanon; Lang, Claudia; Philippsen, Peter

    2011-01-01

    During filamentous fungus development, multinucleated hyphae employ a system for long-range nuclear migration to maintain an equal nuclear density. A decade ago the microtubule motor dynein was shown to play a central role in this process. Previous studies with Ashbya gossypii revealed extensive bidirectional movements and bypassings of nuclei, an autonomous cytoplasmic microtubule (cMT) cytoskeleton emanating from each nucleus, and pulling of nuclei by sliding of cMTs along the cortex. Here, we show that dynein is the sole motor for bidirectional movements and bypassing because these movements are concomitantly decreased in mutants carrying truncations of the dynein heavy-chain DYN1 promoter. The dynactin component Jnm1, the accessory proteins Dyn2 and Ndl1, and the potential dynein cortical anchor Num1 are also involved in the dynamic distribution of nuclei. In their absence, nuclei aggregate to different degrees, whereby the mutants with dense nuclear clusters grow extremely long cMTs. As in budding yeast, we found that dynein is delivered to cMT plus ends, and its activity or processivity is probably controlled by dynactin and Num1. Together with its role in powering nuclear movements, we propose that dynein also plays (directly or indirectly) a role in the control of cMT length. Those combined dynein actions prevent nuclear clustering in A. gossypii and thus reveal a novel cellular role for dynein. PMID:21642510

  7. The chaperone dynein LL1 mediates cytoplasmic transport of empty and mature hepatitis B virus capsids.

    PubMed

    Osseman, Quentin; Gallucci, Lara; Au, Shelly; Cazenave, Christian; Berdance, Elodie; Blondot, Marie-Lise; Cassany, Aurélia; Bégu, Dominique; Ragues, Jessica; Aknin, Cindy; Sominskaya, Irina; Dishlers, Andris; Rabe, Birgit; Anderson, Fenja; Panté, Nelly; Kann, Michael

    2018-03-01

    Hepatitis B virus (HBV) has a DNA genome but replicates within the nucleus by reverse transcription of an RNA pregenome, which is converted to DNA in cytoplasmic capsids. Capsids in this compartment are correlated with inflammation and epitopes of the capsid protein core (Cp) are a major target for T cell-mediated immune responses. We investigated the mechanism of cytoplasmic capsid transport, which is important for infection but also for cytosolic capsid removal. We used virion-derived capsids containing mature rcDNA (matC) and empty capsids (empC). RNA-containing capsids (rnaC) were used as a control. The investigations comprised pull-down assays for identification of cellular interaction partners, immune fluorescence microscopy for their colocalization and electron microscopy after microinjection to determine their biological significance. matC and empC underwent active transport through the cytoplasm towards the nucleus, while rnaC was poorly transported. We identified the dynein light chain LL1 as a functional interaction partner linking capsids to the dynein motor complex and showed that there is no compensatory transport pathway. Using capsid and dynein LL1 mutants we characterized the required domains on the capsid and LL1. This is the first investigation on the detailed molecular mechanism of how matC pass the cytoplasm upon infection and how empC can be actively removed from the cytoplasm into the nucleus. Considering that hepatocytes with cytoplasmic capsids are better recognized by the T cells, we hypothesize that targeting capsid DynLL1-interaction will not only block HBV infection but also stimulate elimination of infected cells. In this study, we identified the molecular details of HBV translocation through the cytoplasm. Our evidence offers a new drug target which could not only inhibit infection but also stimulate immune clearance of HBV infected cells. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B

  8. Distribution of tubulin, kinesin, and dynein in light- and dark-adapted octopus retinas.

    PubMed

    Martinez, J M; Elfarissi, H; De Velasco, B; Ochoa, G H; Miller, A M; Clark, Y M; Matsumoto, B; Robles, L J

    2000-01-01

    Cephalopod retinas exhibit several responses to light and dark adaptation, including rhabdom size changes, photopigment movements, and pigment granule migration. Light- and dark-directed rearrangements of microfilament and microtubule cytoskeletal transport pathways could drive these changes. Recently, we localized actin-binding proteins in light-/dark-adapted octopus rhabdoms and suggested that actin cytoskeletal rearrangements bring about the formation and degradation of rhabdomere microvilli subsets. To determine if the microtubule cytoskeleton and associated motor proteins control the other light/dark changes, we used immunoblotting and immunocytochemical procedures to map the distribution of tubulin, kinesin, and dynein in dorsal and ventral halves of light- and dark-adapted octopus retinas. Immunoblots detected alpha- and beta-tubulin, dynein intermediate chain, and kinesin heavy chain in extracts of whole retinas. Epifluorescence and confocal microscopy showed that the tubulin proteins were distributed throughout the retina with more immunoreactivity in retinas exposed to light. Kinesin localization was heavy in the pigment layer of light- and dark-adapted ventral retinas but was less prominent in the dorsal region. Dynein distribution also varied in dorsal and ventral retinas with more immunoreactivity in light- and dark-adapted ventral retinas and confocal microscopy emphasized the granular nature of this labeling. We suggest that light may regulate the distribution of microtubule cytoskeletal proteins in the octopus retina and that position, dorsal versus ventral, also influences the distribution of motor proteins. The microtubule cytoskeleton is most likely involved in pigment granule migration in the light and dark and with the movement of transport vesicles from the photoreceptor inner segments to the rhabdoms.

  9. Ebola Virus VP35 Interaction with Dynein LC8 Regulates Viral RNA Synthesis

    SciTech Connect

    Luthra, Priya; Jordan, David S.; Leung, Daisy W.

    2015-03-04

    Ebola virus VP35 inhibits alpha/beta interferon production and functions as a viral polymerase cofactor. Previously, the 8-kDa cytoplasmic dynein light chain (LC8) was demonstrated to interact with VP35, but the functional consequences were unclear. Here we demonstrate that the interaction is direct and of high affinity and that binding stabilizes the VP35 N-terminal oligomerization domain and enhances viral RNA synthesis. Mutational analysis demonstrates that VP35 interaction is required for the functional effects of LC8.

  10. A new documentation system for congenital absent digits.

    PubMed

    Jones, Neil F; Kaplan, Jesse

    2012-12-01

    Congenital absent digits continue to be described by many confusing terms and are currently classified in categories I, V, and VI of the International Federation of Societies for Surgery of the Hand classification and seven subclassification systems. Very few classification systems provide any logical basis for surgical reconstruction. The purpose of this study was to develop a simple alphanumerical documentation system to reproducibly describe the morphological or radiographic appearance of congenital absent digits and facilitate communication of these childrens' hand anomalies from one hand surgeon to another. Dorsal and palmar photographs and PA radiographs of 235 hands in 204 children born with congenital absent digits over a 15-year period were analyzed to determine which digital rays were missing and their level of absence. Each hand can be described by three letters, R (radial), C (central), and U (ulnar), as well as numbers 1-5. The first letter and number designate which rays are missing and the second and third letters and numbers designate which rays remain present. There are 15 morphological phenotypes of congenital absent digits. The three most common phenotypes are U4R1 (a thumb but absence of all four fingers), R1U4 (absent thumb), and R5 (aplastic hand). This new documentation system allows hand surgeons to describe the simple morphological or radiographic appearance of congenital absent digits; incorporates all the previous subclassification systems that have attempted to describe congenital absent digits in radial, central, and ulnar deficiencies, symbrachydactyly, and congenital constriction ring syndrome; and has subsequently allowed the development of an algorithm which predicts whether conventional or microsurgical reconstruction is indicated for each specific phenotype.

  11. Dynamic reorganization of Eg5 in the mammalian spindle throughout mitosis requires dynein and TPX2

    PubMed Central

    Gable, Alyssa; Qiu, Minhua; Titus, Janel; Balchand, Sai; Ferenz, Nick P.; Ma, Nan; Collins, Elizabeth S.; Fagerstrom, Carey; Ross, Jennifer L.; Yang, Ge; Wadsworth, Patricia

    2012-01-01

    Kinesin-5 is an essential mitotic motor. However, how its spatial–temporal distribution is regulated in mitosis remains poorly understood. We expressed localization and affinity purification–tagged Eg5 from a mouse bacterial artificial chromosome (this construct was called mEg5) and found its distribution to be tightly regulated throughout mitosis. Fluorescence recovery after photobleaching analysis showed rapid Eg5 turnover throughout mitosis, which cannot be accounted for by microtubule turnover. Total internal reflection fluorescence microscopy and high-resolution, single-particle tracking revealed that mEg5 punctae on both astral and midzone microtubules rapidly bind and unbind. mEg5 punctae on midzone microtubules moved transiently both toward and away from spindle poles. In contrast, mEg5 punctae on astral microtubules moved transiently toward microtubule minus ends during early mitosis but switched to plus end–directed motion during anaphase. These observations explain the poleward accumulation of Eg5 in early mitosis and its redistribution in anaphase. Inhibition of dynein blocked mEg5 movement on astral microtubules, whereas depletion of the Eg5-binding protein TPX2 resulted in plus end–directed mEg5 movement. However, motion of Eg5 on midzone microtubules was not altered. Our results reveal differential and precise spatial and temporal regulation of Eg5 in the spindle mediated by dynein and TPX2. PMID:22337772

  12. Minimal Absent Words in Four Human Genome Assemblies

    PubMed Central

    Garcia, Sara P.; Pinho, Armando J.

    2011-01-01

    Minimal absent words have been computed in genomes of organisms from all domains of life. Here, we aim to contribute to the catalogue of human genomic variation by investigating the variation in number and content of minimal absent words within a species, using four human genome assemblies. We compare the reference human genome GRCh37 assembly, the HuRef assembly of the genome of Craig Venter, the NA12878 assembly from cell line GM12878, and the YH assembly of the genome of a Han Chinese individual. We find the variation in number and content of minimal absent words between assemblies more significant for large and very large minimal absent words, where the biases of sequencing and assembly methodologies become more pronounced. Moreover, we find generally greater similarity between the human genome assemblies sequenced with capillary-based technologies (GRCh37 and HuRef) than between the human genome assemblies sequenced with massively parallel technologies (NA12878 and YH). Finally, as expected, we find the overall variation in number and content of minimal absent words within a species to be generally smaller than the variation between species. PMID:22220210

  13. Dynein mediates retrograde neurofilament transport within axons and anterograde delivery of NFs from perikarya into axons: regulation by multiple phosphorylation events.

    PubMed

    Motil, Jennifer; Chan, Walter K-H; Dubey, Maya; Chaudhury, Pulkit; Pimenta, Aurea; Chylinski, Teresa M; Ortiz, Daniela T; Shea, Thomas B

    2006-05-01

    We examined the respective roles of dynein and kinesin in axonal transport of neurofilaments (NFs). Differentiated NB2a/d1 cells were transfected with green fluorescent protein-NF-M (GFP-M) and dynein function was inhibited by co-transfection with a construct expressing myc-tagged dynamitin, or by intracellular delivery of purified dynamitin and two antibodies against dynein's cargo domain. Monitoring of the bulk distribution of GFP signal within axonal neurites, recovery of GFP signal within photobleached regions, and real-time monitoring of individual NFs/punctate structures each revealed that pertubation of dynein function inhibited retrograde transport and accelerated anterograde, confirming that dynein mediated retrograde axonal transport, while intracellular delivery of two anti-kinesin antibodies selectively inhibited NF anterograde transport. In addition, dynamitin overexpression inhibited the initial translocation of newly-expressed NFs out of perikarya and into neurites, indicating that dynein participated in the initial anterograde delivery of NFs into neurites. Delivery of NFs to the axon hillock inner plasma membrane surface, and their subsequent translocation into neurites, was also prevented by vinblastine-mediated inhibition of microtubule assembly. These data collectively suggest that some NFs enter axons as cargo of microtubues that are themselves undergoing transport into axons via dynein-mediated interactions with the actin cortex and/or larger microtubules. C-terminal NF phosphorylation regulates motor association, since anti-dynein selectively coprecipitated extensively phosphorylated NFs, while anti-kinesin selectively coprecipitated less phosphorylated NFs. In addition, however, the MAP kinase inhibitor PD98059 also inhibited transport of a constitutively-phosphorylated NF construct, indicating that one or more additional, non-NF phosphorylation events also regulated NF association with dynein or kinesin. Copyright 2006 Wiley-Liss, Inc.

  14. Sequential activities of Dynein, Mud and Asp in centrosome-spindle coupling maintain centrosome number upon mitosis.

    PubMed

    Bosveld, Floris; Ainslie, Anna; Bellaïche, Yohanns

    2017-10-15

    Centrosomes nucleate microtubules and are tightly coupled to the bipolar spindle to ensure genome integrity, cell division orientation and centrosome segregation. While the mechanisms of centrosome-dependent microtubule nucleation and bipolar spindle assembly have been the focus of numerous works, less is known about the mechanisms ensuring the centrosome-spindle coupling. The conserved NuMA protein (Mud in Drosophila ) is best known for its role in spindle orientation. Here, we analyzed the role of Mud and two of its interactors, Asp and Dynein, in the regulation of centrosome numbers in Drosophila epithelial cells. We found that Dynein and Mud mainly initiate centrosome-spindle coupling prior to nuclear envelope breakdown (NEB) by promoting correct centrosome positioning or separation, while Asp acts largely independently of Dynein and Mud to maintain centrosome-spindle coupling. Failure in the centrosome-spindle coupling leads to mis-segregation of the two centrosomes into one daughter cell, resulting in cells with supernumerary centrosomes during subsequent divisions. Altogether, we propose that Dynein, Mud and Asp operate sequentially during the cell cycle to ensure efficient centrosome-spindle coupling in mitosis, thereby preventing centrosome mis-segregation to maintain centrosome number. © 2017. Published by The Company of Biologists Ltd.

  15. Chemical structure-guided design of dynapyrazoles, cell-permeable dynein inhibitors with a unique mode of action

    PubMed Central

    Steinman, Jonathan B; Santarossa, Cristina C; Miller, Rand M; Yu, Lola S; Serpinskaya, Anna S; Furukawa, Hideki; Morimoto, Sachie; Tanaka, Yuta; Nishitani, Mitsuyoshi; Asano, Moriteru; Zalyte, Ruta; Ondrus, Alison E; Johnson, Alex G; Ye, Fan; Nachury, Maxence V; Fukase, Yoshiyuki; Aso, Kazuyoshi; Foley, Michael A; Gelfand, Vladimir I; Chen, James K; Carter, Andrew P; Kapoor, Tarun M

    2017-01-01

    Cytoplasmic dyneins are motor proteins in the AAA+ superfamily that transport cellular cargos toward microtubule minus-ends. Recently, ciliobrevins were reported as selective cell-permeable inhibitors of cytoplasmic dyneins. As is often true for first-in-class inhibitors, the use of ciliobrevins has in part been limited by low potency. Moreover, suboptimal chemical properties, such as the potential to isomerize, have hindered efforts to improve ciliobrevins. Here, we characterized the structure of ciliobrevins and designed conformationally constrained isosteres. These studies identified dynapyrazoles, inhibitors more potent than ciliobrevins. At single-digit micromolar concentrations dynapyrazoles block intraflagellar transport in the cilium and lysosome motility in the cytoplasm, processes that depend on cytoplasmic dyneins. Further, we find that while ciliobrevins inhibit both dynein's microtubule-stimulated and basal ATPase activity, dynapyrazoles strongly block only microtubule-stimulated activity. Together, our studies suggest that chemical-structure-based analyses can lead to inhibitors with improved properties and distinct modes of inhibition. DOI: http://dx.doi.org/10.7554/eLife.25174.001 PMID:28524820

  16. Chlamydia trachomatis inclusion membrane protein CT850 interacts with the dynein light chain DYNLT1 (Tctex1).

    PubMed

    Mital, Jeffrey; Lutter, Erika I; Barger, Alexandra C; Dooley, Cheryl A; Hackstadt, Ted

    2015-06-26

    Chlamydia trachomatis actively subverts the minus-end directed microtubule motor, dynein, to traffic along microtubule tracks to the Microtubule Organizing Center (MTOC) where it remains within a membrane bound replicative vacuole for the duration of its intracellular development. Unlike most substrates of the dynein motor, disruption of the dynactin cargo-linking complex by over-expression of the p50 dynamitin subunit does not inhibit C. trachomatis transport. A requirement for chlamydial protein synthesis to initiate this process suggests that a chlamydial product supersedes a requirement for p50 dynamitin. A yeast 2-hybrid system was used to screen the chlamydia inclusion membrane protein CT850 against a HeLa cell cDNA library and identified an interaction with the dynein light chain DYNLT1 (Tctex1). This interaction was at least partially dependent upon an (R/K-R/K-X-X-R/K) motif that is characteristic of DYNLT1 binding domains. CT850 expressed ectopically in HeLa cells localized at the MTOC and this localization is similarly dependent upon the predicted DYNLT1 binding domain. Furthermore, DYNLT1 is enriched at focal concentrations of CT850 on the chlamydial inclusion membrane that are known to interact with dynein and microtubules. Depletion of DYNLT1 disrupts the characteristic association of the inclusion membrane with centrosomes. Collectively, the results suggest that CT850 interacts with DYNLT1 to promote appropriate positioning of the inclusion at the MTOC. Published by Elsevier Inc.

  17. Point Mutations in the Stem Region and the Fourth AAA Domain of Cytoplasmic Dynein Heavy Chain Partially Suppress the Phenotype of NUDF/LIS1 Loss in Aspergillus nidulans

    PubMed Central

    Zhuang, Lei; Zhang, Jun; Xiang, Xin

    2007-01-01

    Cytoplasmic dynein performs multiple cellular tasks but its regulation remains unclear. The dynein heavy chain has a N-terminal stem that binds to other subunits and a C-terminal motor unit that contains six AAA (ATPase associated with cellular activities) domains and a microtubule-binding site located between AAA4 and AAA5. In Aspergillus nidulans, NUDF (a LIS1 homolog) functions in the dynein pathway, and two nudF6 partial suppressors were mapped to the nudA dynein heavy chain locus. Here we identified these two mutations. The nudAL1098F mutation resides in the stem region, and nudAR3086C is in the end of AAA4. These mutations partially suppress the phenotype of nudF deletion but do not suppress the phenotype exhibited by mutants of dynein intermediate chain and Arp1. Surprisingly, the stronger ΔnudF suppressor, nudAR3086C, causes an obvious decrease in the basal level of dynein's ATPase activity and an increase in dynein's distribution along microtubules. Thus, suppression of the ΔnudF phenotype may result from mechanisms other than simply the enhancement of dynein's ATPase activity. The fact that a mutation in the end of AAA4 negatively regulates dynein's ATPase activity but partially compensates for NUDF loss indicates the importance of the AAA4 domain in dynein regulation in vivo. PMID:17237507

  18. The Production of Present and Absent Presences in Education

    ERIC Educational Resources Information Center

    Frelin, Anneli; Grannäs, Jan

    2013-01-01

    Drawing on the distinction between absent and present presences, this article contributes to our understanding of how new managerial and performative discourses are played out in a secondary school context in Sweden. The consequences of numerous educational reforms during the last 20 years include a surge of new independent schools and increased…

  19. 15 CFR 0.735-47 - Decision absent a hearing.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Decision absent a hearing. 0.735-47 Section 0.735-47 Commerce and Foreign Trade Office of the Secretary of Commerce EMPLOYEE RESPONSIBILITIES AND CONDUCT Disciplinary Actions Concerning Post-Employment Conflict of Interest Violations § 0.735-47...

  20. Vampire Selfie: A Curious Case of an Absent Reflection

    ERIC Educational Resources Information Center

    Grossman, Joshua M.

    2014-01-01

    This article presents a puzzle for the optics section of an introductory course on reflections. A teacher could ask students to explain the phenomenon of the "vampire selfie" or the absent reflection. How could that be? What physics caused this curious phenomenon? The article explains light refraction and its effect on what we see and…

  1. Cervical Fusion for Absent Pedicle Syndrome Manifesting with Myelopathy.

    PubMed

    Goodwin, C Rory; Desai, Atman; Khattab, Mohamed H; Elder, Benjamin D; Bydon, Ali; Wolinsky, Jean-Paul

    2016-02-01

    Absent congenital pedicle syndrome is a posterior arch defect characterized by numerous congenital and mechanical abnormalities that result from disconnection of the anterior and posterior columns of the spinal canal. Absent congenital pedicle syndrome is a rare anomaly that is most commonly diagnosed incidentally, after evaluation of minor trauma, or after complaints of chronic neck pain. We report a case of absent congenital pedicle syndrome in a patient who presented with myelopathy and lower extremity weakness and review the literature on the surgical management of this entity. A 32-year-old woman with a history of systemic lupus erythematosus presented to the Neurosurgery Service with progressive weakness in her upper and lower extremities, clonus, and hyperreflexia. Magnetic resonance imaging revealed congenital absence of the pedicles of C2, C3, C4, C5, and C6 with a congenitally narrow canal at C4-5. The patient underwent a staged anterior and posterior cervical decompression and fusion. She was placed in a halo after surgery; at the 1-year follow-up, she was ambulatory with demonstrated improvement in weakness and fusion of her cervical spine. Absent congenital pedicle syndrome is rare, and most reported cases were treated conservatively. Surgical management is reserved for patients with myelopathy or instability. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Absent and Accounted For: Absenteeism and Cooperative Learning

    ERIC Educational Resources Information Center

    Koppenhaver, G. D.

    2006-01-01

    In a small section collaborative learning environment where student work teams promote mutual learning about investments, students limit the opportunity to learn from other students if they are absent from class. Absenteeism not only denies the student the opportunity to learn from others but also denies other members of the student's work team…

  3. Arm CT scan

    MedlinePlus

    CAT scan - arm; Computed axial tomography scan - arm; Computed tomography scan - arm; CT scan - arm ... Healing problems or scar tissue following surgery A CT scan may also be used to guide a surgeon ...

  4. Kaufman oculo-cerebro-facial syndrome in a child with small and absent terminal phalanges and absent nails.

    PubMed

    Kariminejad, Ariana; Ajeawung, Norbert Fonya; Bozorgmehr, Bita; Dionne-Laporte, Alexandre; Molidperee, Sirinart; Najafi, Kimia; Gibbs, Richard A; Lee, Brendan H; Hennekam, Raoul C; Campeau, Philippe M

    2017-04-01

    Kaufman oculo-cerebro-facial syndrome (KOS) is caused by recessive UBE3B mutations and presents with microcephaly, ocular abnormalities, distinctive facial morphology, low cholesterol levels and intellectual disability. We describe a child with microcephaly, brachycephaly, hearing loss, ptosis, blepharophimosis, hypertelorism, cleft palate, multiple renal cysts, absent nails, small or absent terminal phalanges, absent speech and intellectual disability. Syndromes that were initially considered include DOORS syndrome, Coffin-Siris syndrome and Dubowitz syndrome. Clinical investigations coupled with karyotype analysis, array-comparative genomic hybridization, exome and Sanger sequencing were performed to characterize the condition in this child. Sanger sequencing was negative for the DOORS syndrome gene TBC1D24 but exome sequencing identified a homozygous deletion in UBE3B (NM_183415:c.3139_3141del, p.1047_1047del) located within the terminal portion of the HECT domain. This finding coupled with the presence of characteristic features such as brachycephaly, ptosis, blepharophimosis, hypertelorism, short palpebral fissures, cleft palate and developmental delay allowed us to make a diagnosis of KOS. In conclusion, our findings highlight the importance of considering KOS as a differential diagnosis for patients under evaluation for DOORS syndrome and expand the phenotype of KOS to include small or absent terminal phalanges, nails, and the presence of hallux varus and multicystic dysplastic kidneys.

  5. Dynein-Based Accumulation of Membranes Regulates Nuclear Expansion in Xenopus laevis Egg Extracts.

    PubMed

    Hara, Yuki; Merten, Christoph A

    2015-06-08

    Nuclear size changes dynamically during development and has long been observed to correlate with the space surrounding the nucleus, as well as with the volume of the cell. Here we combine an in vitro cell-free system of Xenopus laevis egg extract with microfluidic devices to systematically analyze the effect of spatial constraints. The speed of nuclear expansion depended on the available space surrounding the nucleus up to a threshold volume in the nanoliter range, herein referred to as the nuclear domain. Under spatial constraints smaller than this nuclear domain, the size of microtubule-occupied space surrounding the nucleus turned out to be limiting for the accumulation of membranes around the nucleus via the motor protein dynein, therefore determining the speed of nuclear expansion. This mechanism explains how spatial information surrounding the nucleus, such as the positioning of the nucleus inside the cell, can control nuclear expansion. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Affinity, Avidity, and Kinetics of Target Sequence Binding to LC8 Dynein Light Chain Isoforms*

    PubMed Central

    Radnai, László; Rapali, Péter; Hódi, Zsuzsa; Süveges, Dániel; Molnár, Tamás; Kiss, Bence; Bécsi, Bálint; Erdödi, Ferenc; Buday, László; Kardos, József; Kovács, Mihály; Nyitray, László

    2010-01-01

    LC8 dynein light chain (DYNLL) is a highly conserved eukaryotic hub protein with dozens of binding partners and various functions beyond being a subunit of dynein and myosin Va motor proteins. Here, we compared the kinetic and thermodynamic parameters of binding of both mammalian isoforms, DYNLL1 and DYNLL2, to two putative consensus binding motifs (KXTQTX and XG(I/V)QVD) and report only subtle differences. Peptides containing either of the above motifs bind to DYNLL2 with micromolar affinity, whereas a myosin Va peptide (lacking the conserved Gln) and the noncanonical Pak1 peptide bind with Kd values of 9 and 40 μm, respectively. Binding of the KXTQTX motif is enthalpy-driven, although that of all other peptides is both enthalpy- and entropy-driven. Moreover, the KXTQTX motif shows strikingly slower off-rate constant than the other motifs. As most DYNLL partners are homodimeric, we also assessed the binding of bivalent ligands to DYNLL2. Compared with monovalent ligands, a significant avidity effect was found as follows: Kd values of 37 and 3.5 nm for a dimeric myosin Va fragment and a Leu zipper dimerized KXTQTX motif, respectively. Ligand binding kinetics of DYNLL can best be described by a conformational selection model consisting of a slow isomerization and a rapid binding step. We also studied the binding of the phosphomimetic S88E mutant of DYNLL2 to the dimeric myosin Va fragment, and we found a significantly lower apparent Kd value (3 μm). We conclude that the thermodynamic and kinetic fine-tuning of binding of various ligands to DYNLL could have physiological relevance in its interaction network. PMID:20889982

  7. Integrated pathway analysis of nasopharyngeal carcinoma implicates the axonemal dynein complex in the Malaysian cohort.

    PubMed

    Chin, Yoon-Ming; Tan, Lu Ping; Abdul Aziz, Norazlin; Mushiroda, Taisei; Kubo, Michiaki; Mohd Kornain, Noor Kaslina; Tan, Geok Wee; Khoo, Alan Soo-Beng; Krishnan, Gopala; Pua, Kin-Choo; Yap, Yoke-Yeow; Teo, Soo-Hwang; Lim, Paul Vey-Hong; Nakamura, Yusuke; Lum, Chee Lun; Ng, Ching-Ching

    2016-10-15

    Nasopharyngeal carcinoma (NPC) is an epithelial squamous cell carcinoma on the mucosal lining of the nasopharynx. The etiology of NPC remains elusive despite many reported studies. Most studies employ a single platform approach, neglecting the cumulative influence of both the genome and transcriptome toward NPC development. We aim to employ an integrated pathway approach to identify dysregulated pathways linked to NPC. Our approach combines imputation NPC GWAS data from a Malaysian cohort as well as published expression data GSE12452 from both NPC and non-NPC nasopharynx tissues. Pathway association for GWAS data was performed using MAGENTA while for expression data, GSA-SNP was used with gene p values derived from differential expression values from GEO2R. Our study identified NPC association in the gene ontology (GO) axonemal dynein complex pathway (pGWAS-GSEA  = 1.98 × 10(-2) ; pExpr-GSEA  = 1.27 × 10(-24) ; pBonf-Combined  = 4.15 × 10(-21) ). This association was replicated in a separate cohort using gene expression data from NPC and non-NPC nasopharynx tissues (pAmpliSeq-GSEA  = 6.56 × 10(-4) ). Loss of function in the axonemal dynein complex causes impaired cilia function, leading to poor mucociliary clearance and subsequently upper or lower respiratory tract infection, the former of which includes the nasopharynx. Our approach illustrates the potential use of integrated pathway analysis in detecting gene sets involved in the development of NPC in the Malaysian cohort. © 2016 UICC.

  8. Congenital hypogonadotropic hypogonadism: implications of absent mini-puberty.

    PubMed

    Dwyer, Andrew A; Jayasena, Channa N; Quinton, Richard

    2016-06-01

    The phenomenon known as "mini-puberty" refers to activation of the neonatal hypothalamo-pituitary axis causing serum concentrations of gonadotrophins and testosterone (T) to approach adult male levels. This early neonatal period is a key proliferative window for testicular germ cells and immature Sertoli cells. Although failure to spontaneously initiate (adolescent) puberty is the most evident consequence of a defective gonadotropin-releasing hormone (GnRH) neurosecretory network, absent mini-puberty is also likely to have a major impact on the reproductive phenotype of men with congenital hypogonadotrophic hypogonadism (CHH). Furthermore, the phase of male mini-puberty represents a key window-of-opportunity to identify congenital GnRH deficiency (either isolated CHH, or as part of combined pituitary hormone deficiency) in childhood. Among male neonates exhibiting "red flag" indicators for CHH (i.e. maldescended testes with or without cryptorchidism) a single serum sample (between 4-8 weeks of life) can pinpoint congenital GnRH deficiency far more rapidly and with much greater accuracy than dynamic tests performed in later childhood or adolescence. Potential consequences for missing absent mini-puberty in a male neonate include the lack of monitoring of pubertal progression/lack of progression, and the missed opportunity for early therapeutic intervention. This article will review our current understanding of the mechanisms and clinical consequences of mini-puberty. Furthermore, evidence for the optimal clinical management of patients with absent mini-puberty will be discussed.

  9. TCTEX1D4 Interactome in Human Testis: Unraveling the Function of Dynein Light Chain in Spermatozoa

    PubMed Central

    Freitas, Maria João; Korrodi-Gregório, Luís; Morais-Santos, Filipa; da Cruz e Silva, Edgar

    2014-01-01

    Abstract Studies were designed to identify the TCTEX1D4 interactome in human testis, with the purpose of unraveling putative protein complexes essential to male reproduction and thus novel TCTEX1D4 functions. TCTEX1D4 is a dynein light chain that belongs to the DYNT1/TCTEX1 family. In spermatozoa, it appears to be important to sperm motility, intraflagellar transport, and acrosome reaction. To contribute to the knowledge on TCTEX1D4 function in testis and spermatozoa, a yeast two-hybrid assay was performed in testis, which allowed the identification of 40 novel TCTEX1D4 interactors. Curiously, another dynein light chain, TCTEX1D2, was identified and its existence demonstrated for the first time in human spermatozoa. Immunofluorescence studies proved that TCTEX1D2 is an intra-acrosomal protein also present in the midpiece, suggesting a role in cargo movement in human spermatozoa. Further, an in silico profile of TCTEX1D4 revealed that most TCTEX1D4 interacting proteins were not previously characterized and the ones described present a very broad nature. This reinforces TCTEX1D4 as a dynein light chain that is capable of interacting with a variety of functionally different proteins. These observations collectively contribute to a deeper molecular understanding of the human spermatozoa function. PMID:24606217

  10. Regulation of dynein-driven microtubule sliding by the axonemal protein kinase CK1 in Chlamydomonas flagella

    PubMed Central

    Gokhale, Avanti; Wirschell, Maureen

    2009-01-01

    Experimental analysis of isolated ciliary/flagellar axonemes has implicated the protein kinase casein kinase I (CK1) in regulation of dynein. To test this hypothesis, we developed a novel in vitro reconstitution approach using purified recombinant Chlamydomonas reinhardtii CK1, together with CK1-depleted axonemes from the paralyzed flagellar mutant pf17, which is defective in radial spokes and impaired in dynein-driven microtubule sliding. The CK1 inhibitors (DRB and CK1-7) and solubilization of CK1 restored microtubule sliding in pf17 axonemes, which is consistent with an inhibitory role for CK1. The phosphatase inhibitor microcystin-LR blocked rescue of microtubule sliding, indicating that the axonemal phosphatases, required for rescue, were retained in the CK1-depleted axonemes. Reconstitution of depleted axonemes with purified, recombinant CK1 restored inhibition of microtubule sliding in a DRB– and CK1-7–sensitive manner. In contrast, a purified “kinase-dead” CK1 failed to restore inhibition. These results firmly establish that an axonemal CK1 regulates dynein activity and flagellar motility. PMID:19752022

  11. Finding the Cell Center by a Balance of Dynein and Myosin Pulling and Microtubule Pushing: A Computational Study

    PubMed Central

    Zhu, Jie; Burakov, Anton; Rodionov, Vladimir

    2010-01-01

    The centrosome position in many types of interphase cells is actively maintained in the cell center. Our previous work indicated that the centrosome is kept at the center by pulling force generated by dynein and actin flow produced by myosin contraction and that an unidentified factor that depends on microtubule dynamics destabilizes position of the centrosome. Here, we use modeling to simulate the centrosome positioning based on the idea that the balance of three forces—dyneins pulling along microtubule length, myosin-powered centripetal drag, and microtubules pushing on organelles—is responsible for the centrosome displacement. By comparing numerical predictions with centrosome behavior in wild-type and perturbed interphase cells, we rule out several plausible hypotheses about the nature of the microtubule-based force. We conclude that strong dynein- and weaker myosin-generated forces pull the microtubules inward competing with microtubule plus-ends pushing the microtubule aster outward and that the balance of these forces positions the centrosome at the cell center. The model also predicts that kinesin action could be another outward-pushing force. Simulations demonstrate that the force-balance centering mechanism is robust yet versatile. We use the experimental observations to reverse engineer the characteristic forces and centrosome mobility. PMID:20980619

  12. Tug-of-war of microtubule filaments at the boundary of a kinesin- and dynein-patterned surface

    NASA Astrophysics Data System (ADS)

    Ikuta, Junya; Kamisetty, Nagendra K.; Shintaku, Hirofumi; Kotera, Hidetoshi; Kon, Takahide; Yokokawa, Ryuji

    2014-06-01

    Intracellular cargo is transported by multiple motor proteins. Because of the force balance of motors with mixed polarities, cargo moves bidirectionally to achieve biological functions. Here, we propose a microtubule gliding assay for a tug-of-war study of kinesin and dynein. A boundary of the two motor groups is created by photolithographically patterning gold to selectively attach kinesin to the glass and dynein to the gold surface using a self-assembled monolayer. The relationship between the ratio of two antagonistic motor numbers and the velocity is derived from a force-velocity relationship for each motor to calculate the detachment force and motor backward velocity. Although the tug-of-war involves >100 motors, values are calculated for a single molecule and reflect the collective dynein and non-collective kinesin functions when they work as a team. This assay would be useful for detailed in vitro analysis of intracellular motility, e.g., mitosis, where a large number of motors with mixed polarities are involved.

  13. LIS1 controls mitosis and mitotic spindle organization via the LIS1–NDEL1–dynein complex

    PubMed Central

    Moon, Hyang Mi; Youn, Yong Ha; Pemble, Hayley; Yingling, Jessica; Wittmann, Torsten; Wynshaw-Boris, Anthony

    2014-01-01

    Heterozygous LIS1 mutations are responsible for the human neuronal migration disorder lissencephaly. Mitotic functions of LIS1 have been suggested from many organisms throughout evolution. However, the cellular functions of LIS1 at distinct intracellular compartments such as the centrosome and the cell cortex have not been well defined especially during mitotic cell division. Here, we used detailed cellular approaches and time-lapse live cell imaging of mitosis from Lis1 mutant mouse embryonic fibroblasts to reveal critical roles of LIS1 in mitotic spindle regulation. We found that LIS1 is required for the tight control of chromosome congression and segregation to dictate kinetochore–microtubule (MT) interactions and anaphase progression. In addition, LIS1 is essential for the establishment of mitotic spindle pole integrity by maintaining normal centrosome number. Moreover, LIS1 plays crucial roles in mitotic spindle orientation by increasing the density of astral MT plus-end movements toward the cell cortex, which enhances cortical targeting of LIS1–dynein complex. Overexpression of NDEL1–dynein and MT stabilization rescues spindle orientation defects in Lis1 mutants, demonstrating that mouse LIS1 acts via the LIS1–NDEL1–dynein complex to regulate astral MT plus-ends dynamics and establish proper contacts of MTs with the cell cortex to ensure precise cell division. PMID:24030547

  14. Tug-of-war of microtubule filaments at the boundary of a kinesin- and dynein-patterned surface

    PubMed Central

    Ikuta, Junya; Kamisetty, Nagendra K.; Shintaku, Hirofumi; Kotera, Hidetoshi; Kon, Takahide; Yokokawa, Ryuji

    2014-01-01

    Intracellular cargo is transported by multiple motor proteins. Because of the force balance of motors with mixed polarities, cargo moves bidirectionally to achieve biological functions. Here, we propose a microtubule gliding assay for a tug-of-war study of kinesin and dynein. A boundary of the two motor groups is created by photolithographically patterning gold to selectively attach kinesin to the glass and dynein to the gold surface using a self-assembled monolayer. The relationship between the ratio of two antagonistic motor numbers and the velocity is derived from a force-velocity relationship for each motor to calculate the detachment force and motor backward velocity. Although the tug-of-war involves >100 motors, values are calculated for a single molecule and reflect the collective dynein and non-collective kinesin functions when they work as a team. This assay would be useful for detailed in vitro analysis of intracellular motility, e.g., mitosis, where a large number of motors with mixed polarities are involved. PMID:24923426

  15. Mitotic Chromosome Biorientation in Fission Yeast Is Enhanced by Dynein and a Minus-end–directed, Kinesin-like Protein

    PubMed Central

    Spiridonov, Ilia S.; McIntosh, J. Richard

    2007-01-01

    Chromosome biorientation, the attachment of sister kinetochores to sister spindle poles, is vitally important for accurate chromosome segregation. We have studied this process by following the congression of pole-proximal kinetochores and their subsequent anaphase segregation in fission yeast cells that carry deletions in any or all of this organism's minus end–directed, microtubule-dependent motors: two related kinesin 14s (Pkl1p and Klp2p) and dynein. None of these deletions abolished biorientation, but fewer chromosomes segregated normally without Pkl1p, and to a lesser degree without dynein, than in wild-type cells. In the absence of Pkl1p, which normally localizes to the spindle and its poles, the checkpoint that monitors chromosome biorientation was defective, leading to frequent precocious anaphase. Ultrastructural analysis of mutant mitotic spindles suggests that Pkl1p contributes to error-free biorientation by promoting normal spindle pole organization, whereas dynein helps to anchor a focused bundle of spindle microtubules at the pole. PMID:17409356

  16. Finding the cell center by a balance of dynein and myosin pulling and microtubule pushing: a computational study.

    PubMed

    Zhu, Jie; Burakov, Anton; Rodionov, Vladimir; Mogilner, Alex

    2010-12-01

    The centrosome position in many types of interphase cells is actively maintained in the cell center. Our previous work indicated that the centrosome is kept at the center by pulling force generated by dynein and actin flow produced by myosin contraction and that an unidentified factor that depends on microtubule dynamics destabilizes position of the centrosome. Here, we use modeling to simulate the centrosome positioning based on the idea that the balance of three forces-dyneins pulling along microtubule length, myosin-powered centripetal drag, and microtubules pushing on organelles-is responsible for the centrosome displacement. By comparing numerical predictions with centrosome behavior in wild-type and perturbed interphase cells, we rule out several plausible hypotheses about the nature of the microtubule-based force. We conclude that strong dynein- and weaker myosin-generated forces pull the microtubules inward competing with microtubule plus-ends pushing the microtubule aster outward and that the balance of these forces positions the centrosome at the cell center. The model also predicts that kinesin action could be another outward-pushing force. Simulations demonstrate that the force-balance centering mechanism is robust yet versatile. We use the experimental observations to reverse engineer the characteristic forces and centrosome mobility.

  17. A Cytoplasmic Dynein Heavy Chain Is Required for Oscillatory Nuclear Movement of Meiotic Prophase and Efficient Meiotic Recombination in Fission Yeast

    PubMed Central

    Yamamoto, Ayumu; West, Robert R.; McIntosh, J. Richard; Hiraoka, Yasushi

    1999-01-01

    Meiotic recombination requires pairing of homologous chromosomes, the mechanisms of which remain largely unknown. When pairing occurs during meiotic prophase in fission yeast, the nucleus oscillates between the cell poles driven by astral microtubules. During these oscillations, the telomeres are clustered at the spindle pole body (SPB), located at the leading edge of the moving nucleus and the rest of each chromosome dangles behind. Here, we show that the oscillatory nuclear movement of meiotic prophase is dependent on cytoplasmic dynein. We have cloned the gene encoding a cytoplasmic dynein heavy chain of fission yeast. Most of the cells disrupted for the gene show no gross defect during mitosis and complete meiosis to form four viable spores, but they lack the nuclear movements of meiotic prophase. Thus, the dynein heavy chain is required for these oscillatory movements. Consistent with its essential role in such nuclear movement, dynein heavy chain tagged with green fluorescent protein (GFP) is localized at astral microtubules and the SPB during the movements. In dynein-disrupted cells, meiotic recombination is significantly reduced, indicating that the dynein function is also required for efficient meiotic recombination. In accordance with the reduced recombination, which leads to reduced crossing over, chromosome missegregation is increased in the mutant. Moreover, both the formation of a single cluster of centromeres and the colocalization of homologous regions on a pair of homologous chromosomes are significantly inhibited in the mutant. These results strongly suggest that the dynein-driven nuclear movements of meiotic prophase are necessary for efficient pairing of homologous chromosomes in fission yeast, which in turn promotes efficient meiotic recombination. PMID:10366596

  18. Absent Audiovisual Integration Elicited by Peripheral Stimuli in Parkinson's Disease.

    PubMed

    Ren, Yanna; Suzuki, Keisuke; Yang, Weiping; Ren, Yanling; Wu, Fengxia; Yang, Jiajia; Takahashi, Satoshi; Ejima, Yoshimichi; Wu, Jinglong; Hirata, Koichi

    2018-01-01

    The basal ganglia, which have been shown to be a significant multisensory hub, are disordered in Parkinson's disease (PD). This study was to investigate the audiovisual integration of peripheral stimuli in PD patients with/without sleep disturbances. Thirty-six age-matched normal controls (NC) and 30 PD patients were recruited for an auditory/visual discrimination experiment. The mean response times for each participant were analyzed using repeated measures ANOVA and race model. The results showed that the response to all stimuli was significantly delayed for PD compared to NC (all p < 0.01). The response to audiovisual stimuli was significantly faster than that to unimodal stimuli in both NC and PD ( p < 0.001). Additionally, audiovisual integration was absent in PD; however, it did occur in NC. Further analysis showed that there was no significant audiovisual integration in PD with/without cognitive impairment or in PD with/without sleep disturbances. Furthermore, audiovisual facilitation was not associated with Hoehn and Yahr stage, disease duration, or the presence of sleep disturbances (all p > 0.05). The current results showed that audiovisual multisensory integration for peripheral stimuli is absent in PD regardless of sleep disturbances and further suggested the abnormal audiovisual integration might be a potential early manifestation of PD.

  19. Absent Audiovisual Integration Elicited by Peripheral Stimuli in Parkinson's Disease

    PubMed Central

    Yang, Weiping; Ren, Yanling; Yang, Jiajia; Takahashi, Satoshi; Ejima, Yoshimichi

    2018-01-01

    The basal ganglia, which have been shown to be a significant multisensory hub, are disordered in Parkinson's disease (PD). This study was to investigate the audiovisual integration of peripheral stimuli in PD patients with/without sleep disturbances. Thirty-six age-matched normal controls (NC) and 30 PD patients were recruited for an auditory/visual discrimination experiment. The mean response times for each participant were analyzed using repeated measures ANOVA and race model. The results showed that the response to all stimuli was significantly delayed for PD compared to NC (all p < 0.01). The response to audiovisual stimuli was significantly faster than that to unimodal stimuli in both NC and PD (p < 0.001). Additionally, audiovisual integration was absent in PD; however, it did occur in NC. Further analysis showed that there was no significant audiovisual integration in PD with/without cognitive impairment or in PD with/without sleep disturbances. Furthermore, audiovisual facilitation was not associated with Hoehn and Yahr stage, disease duration, or the presence of sleep disturbances (all p > 0.05). The current results showed that audiovisual multisensory integration for peripheral stimuli is absent in PD regardless of sleep disturbances and further suggested the abnormal audiovisual integration might be a potential early manifestation of PD. PMID:29850014

  20. Absent without leave; a neuroenergetic theory of mind wandering

    PubMed Central

    Killeen, Peter R.

    2013-01-01

    Absent minded people are not under the control of task-relevant stimuli. According to the Neuroenergetics Theory of attention (NeT), this lack of control is often due to fatigue of the relevant processing units in the brain caused by insufficient resupply of the neuron's preferred fuel, lactate, from nearby astrocytes. A simple drift model of information processing accounts for response-time statistics in a paradigm often used to study inattention, the Sustained Attention to Response Task (SART). It is suggested that errors and slowing in this fast-paced, response-engaging task may have little to due with inattention. Slower-paced and less response-demanding tasks give greater license for inattention—aka absent-mindedness, mind-wandering. The basic NeT is therefore extended with an ancillary model of attentional drift and recapture. This Markov model, called NEMA, assumes probability λ of lapses of attention from 1 s to the next, and probability α of drifting back to the attentional state. These parameters measure the strength of attraction back to the task (α), or away to competing mental states or action patterns (λ); their proportion determines the probability of the individual being inattentive at any point in time over the long run. Their values are affected by the fatigue of the brain units they traffic between. The deployment of the model is demonstrated with a data set involving paced responding. PMID:23847559

  1. Curiosity Robotic Arm

    NASA Image and Video Library

    2012-09-06

    This engineering drawing shows the location of the arm on NASA Curiosity rover, in addition to the arm turret, which holds two instruments and three tools. The arm places and holds turret-mounted tools on rock and soil targets.

  2. A High-Throughput Screening Method for Small-Molecule Inhibitors of the Aberrant Mutant SOD1 and Dynein Complex Interaction

    PubMed Central

    Tang, Xiaohu; Seyb, Kathleen I.; Huang, Mickey; Schuman, Eli R.; Shi, Ping; Zhu, Haining; Glicksman, Marcie A.

    2013-01-01

    Aberrant protein-protein interactions are attractive drug targets in a variety of neurodegenerative diseases due to the common pathology of accumulation of protein aggregates. In amyotrophic lateral sclerosis, mutations in SOD1 cause the formation of aggregates and inclusions that may sequester other proteins and disrupt cellular processes. It has been demonstrated that mutant SOD1, but not wild-type SOD1, interacts with the axonal transport motor dynein and that this interaction contributes to motor neuron cell death, suggesting that disrupting this interaction may be a potential therapeutic target. However, it can be challenging to configure a high-throughput screening (HTS)–compatible assay to detect inhibitors of a protein-protein interaction. Here we describe the development and challenges of an HTS for small-molecule inhibitors of the mutant SOD1-dynein interaction. We demonstrate that the interaction can be formed by coexpressing the A4V mutant SOD1 and dynein intermediate complex in cells and that this interaction can be disrupted by compounds added to the cell lysates. Finally, we show that some of the compounds identified from a pilot screen to inhibit the protein-protein interaction with this method specifically disrupt the interaction between the dynein complex and mtSOD1 but not the dynein complex itself when applied to live cells. PMID:22140121

  3. Maternal dazap2 Regulates Germ Granules by Counteracting Dynein in Zebrafish Primordial Germ Cells.

    PubMed

    Forbes, Meredyth M; Rothhämel, Sophie; Jenny, Andreas; Marlow, Florence L

    2015-07-07

    Primordial germ cells (PGCs) are the stem cells of the germline. Generally, germline induction occurs via zygotic factors or the inheritance of maternal determinants called germ plasm (GP). GP is packaged into ribonucleoprotein complexes within oocytes and later promotes the germline fate in embryos. Once PGCs are specified by either mechanism, GP components localize to perinuclear granular-like structures. Although components of zebrafish PGC germ granules have been studied, the maternal factors regulating their assembly and contribution to germ cell development are unknown. Here, we show that the scaffold protein Dazap2 binds to Bucky ball, an essential regulator of oocyte polarity and GP assembly, and colocalizes with the GP in oocytes and in PGCs. Mutational analysis revealed a requirement for maternal Dazap2 (MDazap2) in germ-granule maintenance. Through molecular epistasis analyses, we show that MDazap2 is epistatic to Tdrd7 and maintains germ granules in the embryonic germline by counteracting Dynein activity. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Involvement of Dynein and Spectrin with Early Melanosome Transport and Melanosomal Protein Trafficking

    PubMed Central

    Watabe, Hidenori; Valencia, Julio C.; Le Pape, Elodie; Yamaguchi, Yuji; Nakamura, Masayuki; Rouzaud, François; Hoashi, Toshihiko; Kawa, Yoko; Mizoguchi, Masako; Hearing, Vincent J.

    2007-01-01

    Melanosomes are unique membrane-bound organelles specialized for the synthesis and distribution of melanin. Mechanisms involved in the trafficking of proteins to melanosomes and in the transport of mature pigmented melanosomes to the dendrites of melanocytic cells are being characterized but details about those processes during early stages of melanosome maturation are not well understood. Early melanosomes must remain in the perinuclear area until critical components are assembled. In this study, we characterized the processing of two distinct melanosomal proteins, TYR and Pmel17, to elucidate protein processing in early or late steps of the secretory pathway, respectively, and to determine mechanisms underlying the subcellular localization and transport of early melanosomes. We used immunological, biochemical and molecular approaches to demonstrate that the movement of early melanosomes in the perinuclear area depends primarily on microtubules but not on actin filaments. In contrast, the trafficking of TYR and Pmel17 depends on cytoplasmic dynein and its interaction with the spectrin/ankyrin system which is involved with the sorting of cargo from the plasma membrane. These results provide important clues towards understanding the processes involved with early events in melanosome formation and transport. PMID:17687388

  5. Interventions for replacing missing teeth: partially absent dentition.

    PubMed

    Abt, Elliot; Carr, Alan B; Worthington, Helen V

    2012-02-15

    Management of individuals presenting with partial loss of teeth is a common task for dentists. Outcomes important to the management of missing teeth in the partially absent dentition should be systematically summarized. This review recognizes both the challenges associated with such a summarization and the critical nature of the information for patients. To assess the effects of different prostheses for the treatment of partially absent dentition in terms of the following outcomes: long-term success, function, morbidity and patient satisfaction. We searched the Cochrane Oral Health Group's Trials Register (to 21 March 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), MEDLINE via OVID (1950 to March 2011) and EMBASE via OVID (1980 to March 2011). There were no restrictions regarding language or date of publication. We contacted several authors to identify non-published trials. Randomized controlled trials (RCTs) comparing different methods (including the design and materials used) of treating partial edentulism, with clinically relevant outcomes, were included in this review. Trials reporting only surrogate outcomes, such as plaque accumulation or gingival volume, were excluded from this review. Two review authors independently carried out the screening of eligible studies, assessment of dimensions of quality of trials, and data extraction. Results were expressed as mean differences for continuous data, risk ratios for dichotomous outcomes, and hazard ratios with 95% confidence intervals for time-to-event data. Twenty-one trials met the inclusion criteria for this review. Twenty-four per cent of these were assessed as being at high risk of bias and the remainder were at unclear risk of bias. The clinical heterogeneity among the included studies precluded any attempt at meta-analysis. There was insufficient evidence to determine whether one type of removable dental prosthesis (RDP) was better or worse than

  6. Absent circle of Willis with vascular pollarding in an adult with colpocephaly: A developmental perspective

    PubMed Central

    Verghese, Renjan; Paul, Divyan

    2015-01-01

    Absent circle of Willis (COW) has been described in cases of severe forms of cerebral developmental anomalies such as alobar prosencephaly. However, there are no reports of absent COW in patients with a milder form of cerebral abnormality such as colpocephaly. We report a unique case of an adult with colpocephaly and absent COW and discuss their association from a developmental perspective. PMID:26443299

  7. Improved orthopedic arm joint

    NASA Technical Reports Server (NTRS)

    Dane, D. H.

    1971-01-01

    Joint permits smooth and easy movement of disabled arm and is smaller, lighter and less expensive than previous models. Device is interchangeable and may be used on either arm at the shoulder or at the elbow.

  8. Dynactin-dependent cortical dynein and spherical spindle shape correlate temporally with meiotic spindle rotation in Caenorhabditis elegans

    PubMed Central

    Crowder, Marina E.; Flynn, Jonathan R.; McNally, Karen P.; Cortes, Daniel B.; Price, Kari L.; Kuehnert, Paul A.; Panzica, Michelle T.; Andaya, Armann; Leary, Julie A.; McNally, Francis J.

    2015-01-01

    Oocyte meiotic spindles orient with one pole juxtaposed to the cortex to facilitate extrusion of chromosomes into polar bodies. In Caenorhabditis elegans, these acentriolar spindles initially orient parallel to the cortex and then rotate to the perpendicular orientation. To understand the mechanism of spindle rotation, we characterized events that correlated temporally with rotation, including shortening of the spindle in the pole-to pole axis, which resulted in a nearly spherical spindle at rotation. By analyzing large spindles of polyploid C. elegans and a related nematode species, we found that spindle rotation initiated at a defined spherical shape rather than at a defined spindle length. In addition, dynein accumulated on the cortex just before rotation, and microtubules grew from the spindle with plus ends outward during rotation. Dynactin depletion prevented accumulation of dynein on the cortex and prevented spindle rotation independently of effects on spindle shape. These results support a cortical pulling model in which spindle shape might facilitate rotation because a sphere can rotate without deforming the adjacent elastic cytoplasm. We also present evidence that activation of spindle rotation is promoted by dephosphorylation of the basic domain of p150 dynactin. PMID:26133383

  9. Diverse mitotic functions of the cytoskeletal cross-linking protein Shortstop suggest a role in Dynein/Dynactin activity

    PubMed Central

    Dewey, Evan B.; Johnston, Christopher A.

    2017-01-01

    Proper assembly and orientation of the bipolar mitotic spindle is critical to the fidelity of cell division. Mitotic precision fundamentally contributes to cell fate specification, tissue development and homeostasis, and chromosome distribution within daughter cells. Defects in these events are thought to contribute to several human diseases. The underlying mechanisms that function in spindle morphogenesis and positioning remain incompletely defined, however. Here we describe diverse roles for the actin-microtubule cross-linker Shortstop (Shot) in mitotic spindle function in Drosophila. Shot localizes to mitotic spindle poles, and its knockdown results in an unfocused spindle pole morphology and a disruption of proper spindle orientation. Loss of Shot also leads to chromosome congression defects, cell cycle progression delay, and defective chromosome segregation during anaphase. These mitotic errors trigger apoptosis in Drosophila epithelial tissue, and blocking this apoptotic response results in a marked induction of the epithelial–mesenchymal transition marker MMP-1. The actin-binding domain of Shot directly interacts with Actin-related protein-1 (Arp-1), a key component of the Dynein/Dynactin complex. Knockdown of Arp-1 phenocopies Shot loss universally, whereas chemical disruption of F-actin does so selectively. Our work highlights novel roles for Shot in mitosis and suggests a mechanism involving Dynein/Dynactin activation. PMID:28747439

  10. Phosphorylation of Nlp by Plk1 negatively regulates its dynein-dynactin-dependent targeting to the centrosome.

    PubMed

    Casenghi, Martina; Barr, Francis A; Nigg, Erich A

    2005-11-01

    When cells enter mitosis the microtubule (MT) network undergoes a profound rearrangement, in part due to alterations in the MT nucleating and anchoring properties of the centrosome. Ninein and the ninein-like protein (Nlp) are centrosomal proteins involved in MT organisation in interphase cells. We show that the overexpression of these two proteins induces the fragmentation of the Golgi, and causes lysosomes to disperse toward the cell periphery. The ability of Nlp and ninein to perturb the cytoplasmic distribution of these organelles depends on their ability to interact with the dynein-dynactin motor complex. Our data also indicate that dynactin is required for the targeting of Nlp and ninein to the centrosome. Furthermore, phosphorylation of Nlp by the polo-like kinase 1 (Plk1) negatively regulates its association with dynactin. These findings uncover a mechanism through which Plk1 helps to coordinate changes in MT organisation with cell cycle progression, by controlling the dynein-dynactin-dependent transport of centrosomal proteins.

  11. Perspectives on Arms Control

    DTIC Science & Technology

    2004-07-01

    perspective. He traces the important and integral place of arms control diplomacy to United States traditions, and projects continuing relevance for... The second is commonality surrounding the ongoing arms control process on nuclear weapons and missiles between America and Russia that needs...summits were built around arms control discussions, large delegations met frequently in places like Geneva, and even trivial changes in the arms

  12. Evolution of robotic arms.

    PubMed

    Moran, Michael E

    2007-01-01

    The foundation of surgical robotics is in the development of the robotic arm. This is a thorough review of the literature on the nature and development of this device with emphasis on surgical applications. We have reviewed the published literature and classified robotic arms by their application: show, industrial application, medical application, etc. There is a definite trend in the manufacture of robotic arms toward more dextrous devices, more degrees-of-freedom, and capabilities beyond the human arm. da Vinci designed the first sophisticated robotic arm in 1495 with four degrees-of-freedom and an analog on-board controller supplying power and programmability. von Kemplen's chess-playing automaton left arm was quite sophisticated. Unimate introduced the first industrial robotic arm in 1961, it has subsequently evolved into the PUMA arm. In 1963 the Rancho arm was designed; Minsky's Tentacle arm appeared in 1968, Scheinman's Stanford arm in 1969, and MIT's Silver arm in 1974. Aird became the first cyborg human with a robotic arm in 1993. In 2000 Miguel Nicolalis redefined possible man-machine capacity in his work on cerebral implantation in owl-monkeys directly interfacing with robotic arms both locally and at a distance. The robotic arm is the end-effector of robotic systems and currently is the hallmark feature of the da Vinci Surgical System making its entrance into surgical application. But, despite the potential advantages of this computer-controlled master-slave system, robotic arms have definite limitations. Ongoing work in robotics has many potential solutions to the drawbacks of current robotic surgical systems.

  13. TCLS ARM for Space

    NASA Astrophysics Data System (ADS)

    Poupat, Jean-Luc; Leroy, Benoit; Helfers, Tim

    2016-08-01

    The TCLS ARM FOR SPACE proposal was an answer to the H2020 topic "COMPET-6-2014: Bottom-up Space Technologies at low TRL".This paper presents the status on this H2020 TCLS ARM FOR SPACE initiative led by Airbus DS and which aims at fostering the use of European technology such as ARM processing for Space.

  14. Arm Injuries and Disorders

    MedlinePlus

    ... your body, three of them are in your arm: the humerus, radius, and ulna. Your arms are also made up of muscles, joints, tendons, ... Injuries to any of these parts of the arm can occur during sports, a fall, or an ...

  15. Transport of fungal RAB11 secretory vesicles involves myosin-5, dynein/dynactin/p25, and kinesin-1 and is independent of kinesin-3

    PubMed Central

    Peñalva, Miguel A.; Zhang, Jun; Xiang, Xin; Pantazopoulou, Areti

    2017-01-01

    Hyphal tip cells of the fungus Aspergillus nidulans are useful for studying long-range intracellular traffic. Post-Golgi secretory vesicles (SVs) containing the RAB11 orthologue RabE engage myosin-5 as well as plus end– and minus end–directed microtubule motors, providing an experimental system with which to investigate the interplay between microtubule and actin motors acting on the same cargo. By exploiting the fact that depolymerization of F-actin unleashes SVs focused at the apex by myosin-5 to microtubule-dependent motors, we establish that the minus end–directed transport of SVs requires the dynein/dynactin supercomplex. This minus end–directed transport is largely unaffected by genetic ablation of the Hook complex adapting early endosomes (EEs) to dynein but absolutely requires p25 in dynactin. Thus dynein recruitment to two different membranous cargoes, namely EEs and SVs, requires p25, highlighting the importance of the dynactin pointed-end complex to scaffold cargoes. Finally, by studying the behavior of SVs and EEs in null and rigor mutants of kinesin-3 and kinesin-1 (UncA and KinA, respectively), we demonstrate that KinA is the major kinesin mediating the anterograde transport of SVs. Therefore SVs arrive at the apex of A. nidulans by anterograde transport involving cooperation of kinesin-1 with myosin-5 and can move away from the apex powered by dynein. PMID:28209731

  16. Dynein light chain regulates adaptive and innate B cell development by distinctive genetic mechanisms

    PubMed Central

    King, Ashleigh; Li, Lingli; Wong, David M.; Liu, Rui; Bamford, Rebecca; Strasser, Andreas

    2017-01-01

    Mechanistic differences in the development and function of adaptive, high-affinity antibody-producing B-2 cells and innate-like, “natural” antibody-producing B-1a cells remain poorly understood. Here we show that the multi-functional dynein light chain (DYNLL1/LC8) plays important roles in the establishment of B-1a cells in the peritoneal cavity and in the ongoing development of B-2 lymphoid cells in the bone marrow of mice. Epistasis analyses indicate that Dynll1 regulates B-1a and early B-2 cell development in a single, linear pathway with its direct transcriptional activator ASCIZ (ATMIN/ZNF822), and that the two genes also have complementary functions during late B-2 cell development. The B-2 cell defects caused by loss of DYNLL1 were associated with lower levels of the anti-apoptotic protein BCL-2, and could be supressed by deletion of pro-apoptotic BIM which is negatively regulated by both DYNLL1 and BCL-2. Defects in B cell development caused by loss of DYNLL1 could also be partially suppressed by a pre-arranged SWHEL Igm-B cell receptor transgene. In contrast to the rescue of B-2 cell numbers, the B-1a cell deficiency in Dynll1-deleted mice could not be suppressed by the loss of Bim, and was further compounded by the SWHEL transgene. Conversely, oncogenic MYC expression, which is synthetic lethal with Dynll1 deletion in B-2 cells, did not further reduce B-1a cell numbers in Dynll1-defcient mice. Finally, we found that the ASCIZ-DYNLL1 axis was also required for the early-juvenile development of aggressive MYC-driven and p53-deficient B cell lymphomas. These results identify ASCIZ and DYNLL1 as the core of a transcriptional circuit that differentially regulates the development of the B-1a and B-2 B lymphoid cell lineages and plays a critical role in lymphomagenesis. PMID:28922373

  17. Effectiveness of a dynein team in a tug of war helped by reduced load sensitivity of detachment: evidence from the study of bidirectional endosome transport in D. discoideum.

    PubMed

    Bhat, Deepak; Gopalakrishnan, Manoj

    2012-08-01

    Bidirectional cargo transport by molecular motors in cells is a complex phenomenon in which the cargo (usually a vesicle) alternately moves in retrograde and anterograde directions. In this case, teams of oppositely pulling motors (e.g., kinesin and dynein) bind to the cargo, simultaneously, and 'coordinate' their activity such that the motion consists of spells of positively and negatively directed segments, separated by pauses of varying duration. A set of recent experiments have analyzed the bidirectional motion of endosomes in the amoeba D. discoideum in detail. It was found that in between directional switches, a team of five to six dyneins stall a cargo against a stronger kinesin in a tug of war, which lasts for almost a second. As the mean detachment time of a kinesin under its stall load was also observed to be ∼1 s, we infer that the collective detachment time of the dynein assembly must also be similar. Here, we analyze this inference from a modeling perspective, using experimentally measured single-molecule parameters as inputs. We find that the commonly assumed exponential load-dependent detachment rate is inconsistent with observations, as it predicts that a five-dynein assembly will detach under its combined stall load in less than a hundredth of a second. A modified model where the load-dependent unbinding rate is assumed to saturate at stall-force level for super-stall loads gives results which are in agreement with experimental data. Our analysis suggests that the load-dependent detachment of a dynein in a team is qualitatively different at sub-stall and super-stall loads, a conclusion which is likely to have implications in other situations involving collective effects of many motors.

  18. Live Cell Imaging Reveals Differential Modifications to Cytoplasmic Dynein Properties by Phospho- and Dephospho-mimic Mutations of the Intermediate Chain 2C S84

    PubMed Central

    Blasier, Kiev R.; Humsi, Michael K.; Ha, Junghoon; Ross, Mitchell W.; Smiley, W. Russell; Inamdar, Nirja A.; Mitchell, David J.; Lo, Kevin W.-H.; Pfister, K. Kevin

    2014-01-01

    Cytoplasmic dynein is a multi-subunit motor protein responsible for intracellular cargo transport toward microtubule minus ends. There are multiple isoforms of the dynein intermediate chain (DYNC1I, IC) which is encoded by two genes. One way to regulate cytoplasmic dynein is by IC phosphorylation. The IC-2C isoform is expressed in all cells and the functional significance of phosphorylation on IC-2C serine 84 was investigated using live cell imaging of fluorescent protein-tagged wild type IC-2C (WT) and phospho- and dephospho-mimic mutant isoforms in axonal transport model systems. Both mutations modulated dynein functional properties. The dephospho-mimic mutant IC-2C S84A had greater co-localization with mitochondria than IC-2C wild-type (WT) or the phospho-mimic mutant IC-2C S84D. The dephospho-mimic mutant IC-2C S84A was also more likely to be motile than the phospho-mimic mutant IC-2C S84D or IC-2C WT. In contrast, the phospho-mimic mutant IC-2C S84D mutant was more likely to move in the retrograde direction than was the IC-2C S84A mutant. The phospho-mimic IC-2C S84D was also as likely as IC-2C WT to co-localize with mitochondria. Both the S84D phospho- and S84A, dephospho-mimic mutants were found to be capable of microtubule minus end directed (retrograde) movement in axons. They were also observed to be passively transported in the anterograde direction. These data suggest that the IC-2C S84 has a role in modulating dynein properties. PMID:24798412

  19. Inhibition of microtubules and dynein rescues human immunodeficiency virus type 1 from owl monkey TRIMCyp-mediated restriction in a cellular context-specific fashion.

    PubMed

    Pawlica, Paulina; Dufour, Caroline; Berthoux, Lionel

    2015-04-01

    IFN-induced restriction factors can significantly affect the replicative capacity of retroviruses in mammals. TRIM5α (tripartite motif protein 5, isoform α) is a restriction factor that acts at early stages of the virus life cycle by intercepting and destabilizing incoming retroviral cores. Sensitivity to TRIM5α maps to the N-terminal domain of the retroviral capsid proteins. In several New World and Old World monkey species, independent events of retrotransposon-mediated insertion of the cyclophilin A (CypA)-coding sequence in the trim5 gene have given rise to TRIMCyp (also called TRIM5-CypA), a hybrid protein that is active against some lentiviruses in a species-specific fashion. In particular, TRIMCyp from the owl monkey (omkTRIMCyp) very efficiently inhibits human immunodeficiency virus type 1 (HIV-1). Previously, we showed that disrupting the integrity of microtubules (MTs) and of cytoplasmic dynein complexes partially rescued replication of retroviruses, including HIV-1, from restriction mediated by TRIM5α. Here, we showed that efficient restriction of HIV-1 by omkTRIMCyp was similarly dependent on the MT network and on dynein complexes, but in a context-dependent fashion. When omkTRIMCyp was expressed in human HeLa cells, restriction was partially counteracted by pharmacological agents targeting MTs or by small interfering RNA-mediated inhibition of dynein. The same drugs (nocodazole and paclitaxel) also rescued HIV-1 from restriction in cat CRFK cells, although to a lesser extent. Strikingly, neither nocodazole, paclitaxel nor depletion of the dynein heavy chain had a significant effect on the restriction of HIV-1 in an owl monkey cell line. These results suggested the existence of cell-specific functional interactions between MTs/dynein and TRIMCyp. © 2015 The Authors.

  20. bicoid mRNA localises to the Drosophila oocyte anterior by random Dynein-mediated transport and anchoring

    PubMed Central

    Trovisco, Vítor; Belaya, Katsiaryna; Nashchekin, Dmitry; Irion, Uwe; Sirinakis, George; Butler, Richard; Lee, Jack J; Gavis, Elizabeth R; St Johnston, Daniel

    2016-01-01

    bicoid mRNA localises to the Drosophila oocyte anterior from stage 9 of oogenesis onwards to provide a local source for Bicoid protein for embryonic patterning. Live imaging at stage 9 reveals that bicoid mRNA particles undergo rapid Dynein-dependent movements near the oocyte anterior, but with no directional bias. Furthermore, bicoid mRNA localises normally in shot2A2, which abolishes the polarised microtubule organisation. FRAP and photo-conversion experiments demonstrate that the RNA is stably anchored at the anterior, independently of microtubules. Thus, bicoid mRNA is localised by random active transport and anterior anchoring. Super-resolution imaging reveals that bicoid mRNA forms 110–120 nm particles with variable RNA content, but constant size. These particles appear to be well-defined structures that package the RNA for transport and anchoring. DOI: http://dx.doi.org/10.7554/eLife.17537.001 PMID:27791980

  1. Radial arm strike rail

    DOEpatents

    McKeown, Mark H.; Beason, Steven C.

    1991-01-01

    The radial arm strike rail assembly is a system for measurement of bearings, directions, and stereophotography for geologic mapping, particularly where magnetic compasses are not appropriate. The radial arm, pivoting around a shaft axis, provides a reference direction determination for geologic mapping and bearing or direction determination. The centerable and levelable pedestal provide a base for the radial arm strike rail and the telescoping camera pedestal. The telescoping feature of the radial arm strike rail allows positioning the end of the rail for strike direction or bearing measurement with a goniometer.

  2. Diverse mitotic functions of the cytoskeletal cross-linking protein Shortstop suggest a role in Dynein/Dynactin activity.

    PubMed

    Dewey, Evan B; Johnston, Christopher A

    2017-09-15

    Proper assembly and orientation of the bipolar mitotic spindle is critical to the fidelity of cell division. Mitotic precision fundamentally contributes to cell fate specification, tissue development and homeostasis, and chromosome distribution within daughter cells. Defects in these events are thought to contribute to several human diseases. The underlying mechanisms that function in spindle morphogenesis and positioning remain incompletely defined, however. Here we describe diverse roles for the actin-microtubule cross-linker Shortstop (Shot) in mitotic spindle function in Drosophila Shot localizes to mitotic spindle poles, and its knockdown results in an unfocused spindle pole morphology and a disruption of proper spindle orientation. Loss of Shot also leads to chromosome congression defects, cell cycle progression delay, and defective chromosome segregation during anaphase. These mitotic errors trigger apoptosis in Drosophila epithelial tissue, and blocking this apoptotic response results in a marked induction of the epithelial-mesenchymal transition marker MMP-1. The actin-binding domain of Shot directly interacts with Actin-related protein-1 (Arp-1), a key component of the Dynein/Dynactin complex. Knockdown of Arp-1 phenocopies Shot loss universally, whereas chemical disruption of F-actin does so selectively. Our work highlights novel roles for Shot in mitosis and suggests a mechanism involving Dynein/Dynactin activation. © 2017 Dewey and Johnston. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  3. Integrated proteomics identified novel activation of dynein IC2-GR-COX-1 signaling in neurofibromatosis type I (NF1) disease model cells.

    PubMed

    Hirayama, Mio; Kobayashi, Daiki; Mizuguchi, Souhei; Morikawa, Takashi; Nagayama, Megumi; Midorikawa, Uichi; Wilson, Masayo M; Nambu, Akiko N; Yoshizawa, Akiyasu C; Kawano, Shin; Araki, Norie

    2013-05-01

    Neurofibromatosis type 1 (NF1) tumor suppressor gene product, neurofibromin, functions in part as a Ras-GAP, and though its loss is implicated in the neuronal abnormality of NF1 patients, its precise cellular function remains unclear. To study the molecular mechanism of NF1 pathogenesis, we prepared NF1 gene knockdown (KD) PC12 cells, as a NF1 disease model, and analyzed their molecular (gene and protein) expression profiles with a unique integrated proteomics approach, comprising iTRAQ, 2D-DIGE, and DNA microarrays, using an integrated protein and gene expression analysis chart (iPEACH). In NF1-KD PC12 cells showing abnormal neuronal differentiation after NGF treatment, of 3198 molecules quantitatively identified and listed in iPEACH, 97 molecules continuously up- or down-regulated over time were extracted. Pathway and network analysis further revealed overrepresentation of calcium signaling and transcriptional regulation by glucocorticoid receptor (GR) in the up-regulated protein set, whereas nerve system development was overrepresented in the down-regulated protein set. The novel up-regulated network we discovered, "dynein IC2-GR-COX-1 signaling," was then examined in NF1-KD cells. Validation studies confirmed that NF1 knockdown induces altered splicing and phosphorylation patterns of dynein IC2 isomers, up-regulation and accumulation of nuclear GR, and increased COX-1 expression in NGF-treated cells. Moreover, the neurite retraction phenotype observed in NF1-KD cells was significantly recovered by knockdown of the dynein IC2-C isoform and COX-1. In addition, dynein IC2 siRNA significantly inhibited nuclear translocation and accumulation of GR and up-regulation of COX-1 expression. These results suggest that dynein IC2 up-regulates GR nuclear translocation and accumulation, and subsequently causes increased COX-1 expression, in this NF1 disease model. Our integrated proteomics strategy, which combines multiple approaches, demonstrates that NF1-related neural

  4. Sometimes two arms are enough--an unusual life-stage in brittle stars (Echinodermata: Ophiuroidea).

    PubMed

    Stöhr, Sabine; Alme, Øydis

    2015-08-03

    Off West Africa (Angola-Morocco), benthos samples were collected in the years 2005-2012. These contained 124 specimens of brittle stars with two long arms and three extremely short or absent arms and an elongated, narrow disc. These unusual brittle stars, as well as 33 specimens with five fully developed arms, were identified as Amphiura ungulata. The specimens with unequal arms were juvenile stages, whereas adults had five equal arms. The large number of specimens with unequal arms suggests that this condition is not the result of damage and regeneration, but a normal growth pattern in this species. This study documents the morphology by SEM, amends the species description, and discusses possible explanations for the evolution of this condition. Although brittle star species with unequal arm growth have been reported, this is an extreme case that was unknown before this study.

  5. Successful Black Men from Absent-Father Homes and Their Resilient Single Mothers: A Phenomenological Study

    ERIC Educational Resources Information Center

    Wilson, Angie D.; Henriksen, Richard C.; Bustamante, Rebecca; Irby, Beverly

    2016-01-01

    The phenomenon of absent fathers is a common occurrence in today's homes that appears to be escalating, especially in Black households across the United States. The purpose of this study was to describe the lived experiences of successful Black men who were raised in absent-father homes as well as the lived experiences of their resilient single…

  6. Disneyland Dads, Disneyland Moms? How Nonresident Parents Spend Time with Absent Children.

    ERIC Educational Resources Information Center

    Stewart, Susan D.

    1999-01-01

    Examines gender differences in how nonresident parents spend time with their absent children. Results suggest that nonresident mothers and fathers exhibit a similar pattern of participation in activities with their absent children. Most nonresident parents either engage in only leisure activities with their children or have no contact. (Author/MKA)

  7. 42 CFR 410.175 - Alien absent from the United States.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 2 2014-10-01 2014-10-01 false Alien absent from the United States. 410.175... Alien absent from the United States. (a) Medicare does not pay Part B benefits for services furnished to... during the first full calendar month the alien is back in the United States. [53 FR 6634, Mar. 2, 1988] ...

  8. 42 CFR 410.175 - Alien absent from the United States.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 2 2013-10-01 2013-10-01 false Alien absent from the United States. 410.175... Alien absent from the United States. (a) Medicare does not pay Part B benefits for services furnished to... during the first full calendar month the alien is back in the United States. [53 FR 6634, Mar. 2, 1988] ...

  9. 42 CFR 410.175 - Alien absent from the United States.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 2 2012-10-01 2012-10-01 false Alien absent from the United States. 410.175... Alien absent from the United States. (a) Medicare does not pay Part B benefits for services furnished to... during the first full calendar month the alien is back in the United States. [53 FR 6634, Mar. 2, 1988] ...

  10. 42 CFR 410.175 - Alien absent from the United States.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 2 2011-10-01 2011-10-01 false Alien absent from the United States. 410.175... Alien absent from the United States. (a) Medicare does not pay Part B benefits for services furnished to... during the first full calendar month the alien is back in the United States. [53 FR 6634, Mar. 2, 1988] ...

  11. 42 CFR 410.175 - Alien absent from the United States.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Alien absent from the United States. 410.175... Alien absent from the United States. (a) Medicare does not pay Part B benefits for services furnished to... during the first full calendar month the alien is back in the United States. [53 FR 6634, Mar. 2, 1988] ...

  12. Causal Attributions as Predictors of Academic Achievement in Father-Absent Children.

    ERIC Educational Resources Information Center

    Salzman, Stephanie A.

    The purpose of this study was to examine the potential impact of maternal attributions and self-attributions on the academic achievement of father-absent children in comparison to commonly identified family interaction and demographic variables. Subjects included 33 male and 34 female father-absent sixth graders (mean age of 11.6 years) and their…

  13. ARM Mentor Selection Process

    SciTech Connect

    Sisterson, D. L.

    2015-10-01

    The Atmospheric Radiation Measurement (ARM) Program was created in 1989 with funding from the U.S. Department of Energy (DOE) to develop several highly instrumented ground stations to study cloud formation processes and their influence on radiative transfer. In 2003, the ARM Program became a national scientific user facility, known as the ARM Climate Research Facility. This scientific infrastructure provides for fixed sites, mobile facilities, an aerial facility, and a data archive available for use by scientists worldwide through the ARM Climate Research Facility—a scientific user facility. The ARM Climate Research Facility currently operates more than 300 instrument systems that providemore » ground-based observations of the atmospheric column. To keep ARM at the forefront of climate observations, the ARM infrastructure depends heavily on instrument scientists and engineers, also known as lead mentors. Lead mentors must have an excellent understanding of in situ and remote-sensing instrumentation theory and operation and have comprehensive knowledge of critical scale-dependent atmospheric processes. They must also possess the technical and analytical skills to develop new data retrievals that provide innovative approaches for creating research-quality data sets. The ARM Climate Research Facility is seeking the best overall qualified candidate who can fulfill lead mentor requirements in a timely manner.« less

  14. Sliding of microtubules by a team of dynein motors: Understanding the effect of spatial distribution of motor tails and mutual exclusion of motor heads on microtubules

    NASA Astrophysics Data System (ADS)

    Singh, Hanumant Pratap; Takshak, Anjneya; Mall, Utkarsh; Kunwar, Ambarish

    2016-06-01

    Molecular motors are natural nanomachines that use the free energy released from ATP hydrolysis to generate mechanical forces. Cytoplasmic dynein motors often work collectively as a team to drive important processes such as axonal growth, proplatelet formation and mitosis, as forces generated by single motors are insufficient. A large team of dynein motors is used to slide cytoskeletal microtubules with respect to one another during the process of proplatelet formation and axonal growth. These motors attach to a cargo microtubule via their tail domains, undergo the process of detachment and reattachment of their head domains on another track microtubule, while sliding the cargo microtubule along the track. Traditional continuum/mean-field approaches used in the past are not ideal for studying the sliding mechanism of microtubules, as they ignore spatial and temporal fluctuations due to different possible distributions of motor tails on cargo filament, as well as binding/unbinding of motors from their track. Therefore, these models cannot be used to address important questions such as how the distribution of motor tails on microtubules, or how the mutual exclusion of motor heads on microtubule tracks affects the sliding velocity of cargo microtubule. To answer these, here we use a computational stochastic model where we model each dynein motor explicitly. In our model, we use both random as well as uniform distributions of dynein motors on cargo microtubule, as well as mutual exclusion of motors on microtubule tracks. We find that sliding velocities are least affected by the distribution of motor tails on microtubules, whereas they are greatly affected by mutual exclusion of motor heads on microtubule tracks. We also find that sliding velocity depends on the length of cargo microtubule if mutual exclusion among motor heads is considered.

  15. The Novel Zinc Finger Protein dASCIZ Regulates Mitosis in Drosophila via an Essential Role in Dynein Light-Chain Expression

    PubMed Central

    Zaytseva, Olga; Tenis, Nora; Mitchell, Naomi; Kanno, Shin-ichiro; Yasui, Akira; Heierhorst, Jörg; Quinn, Leonie M

    2014-01-01

    The essential zinc finger protein ASCIZ (also known as ATMIN, ZNF822) plays critical roles during lung organogenesis and B cell development in mice, where it regulates the expression of dynein light chain (DYNLL1/LC8), but its functions in other species including invertebrates are largely unknown. Here we report the identification of the Drosophila ortholog of ASCIZ (dASCIZ) and show that loss of dASCIZ function leads to pronounced mitotic delays with centrosome and spindle positioning defects during development, reminiscent of impaired dynein motor functions. Interestingly, similar mitotic and developmental defects were observed upon knockdown of the DYNLL/LC8-type dynein light chain Cutup (Ctp), and dASCIZ loss-of-function phenotypes could be suppressed by ectopic Ctp expression. Consistent with a genetic function of dASCIZ upstream of Ctp, we show that loss of dASCIZ led to reduced endogenous Ctp mRNA and protein levels and dramatically reduced Ctp–LacZ reporter gene activity in vivo, indicating that dASCIZ regulates development and mitosis as a Ctp transcription factor. We speculate that the more severe mitotic defects in the absence of ASCIZ in flies compared to mice may be due to redundancy with a second, ASCIZ-independent, Dynll2 gene in mammals in contrast to a single Ctp gene in Drosophila. Altogether, our data demonstrate that ASCIZ is an evolutionary highly conserved transcriptional regulator of dynein light-chain levels and a novel regulator of mitosis in flies. PMID:24336747

  16. Functional Analysis of Human Microtubule-based Motor Proteins, the Kinesins and Dyneins, in Mitosis/Cytokinesis Using RNA InterferenceD⃞V⃞

    PubMed Central

    Zhu, Changjun; Zhao, Jian; Bibikova, Marina; Leverson, Joel D.; Bossy-Wetzel, Ella; Fan, Jian-Bing; Abraham, Robert T.; Jiang, Wei

    2005-01-01

    Microtubule (MT)-based motor proteins, kinesins and dyneins, play important roles in multiple cellular processes including cell division. In this study, we describe the generation and use of an Escherichia coli RNase III-prepared human kinesin/dynein esiRNA library to systematically analyze the functions of all human kinesin/dynein MT motor proteins. Our results indicate that at least 12 kinesins are involved in mitosis and cytokinesis. Eg5 (a member of the kinesin-5 family), Kif2A (a member of the kinesin-13 family), and KifC1 (a member of the kinesin-14 family) are crucial for spindle formation; KifC1, MCAK (a member of the kinesin-13 family), CENP-E (a member of the kinesin-7 family), Kif14 (a member of the kinesin-3 family), Kif18 (a member of the kinesin-8 family), and Kid (a member of the kinesin-10 family) are required for chromosome congression and alignment; Kif4A and Kif4B (members of the kinesin-4 family) have roles in anaphase spindle dynamics; and Kif4A, Kif4B, MKLP1, and MKLP2 (members of the kinesin-6 family) are essential for cytokinesis. Using immunofluorescence analysis, time-lapse microscopy, and rescue experiments, we investigate the roles of these 12 kinesins in detail. PMID:15843429

  17. Sweating - absent

    MedlinePlus

    ... page, please enable JavaScript. An abnormal lack of sweat in response to heat may be harmful, because ... diseases or scarring of the skin that block sweat glands Trauma to sweat glands Use of certain ...

  18. Absent right common carotid artery associated with aberrant right subclavian artery.

    PubMed

    Uchino, Akira; Uwabe, Kazuhiko; Osawa, Iichiro

    2018-06-01

    Rarely, the external and internal carotid arteries arise separately from the brachiocephalic trunk and right subclavian artery (SA) or the aortic arch and reflect the absence of a common carotid artery (CCA). We report a 45-year-old man with absent right CCA associated with aberrant right SA, an extremely rare combination, diagnosed by computed tomography (CT) angiography during follow-up for postoperative aortic dissection. Retrospective careful observation of preoperative postcontrast CT revealed the absent right CCA. Previously reported arch variations associated with absent CCA include cervical aortic arch, double aortic arch, and right aortic arch.

  19. Bruising Hands and Arms

    MedlinePlus

    ... arms is common. Dermatologists call it 'actinic purpura', 'solar purpura' or 'Bateman's purpura'. These flat blotches start ... lesion or disease, please consult a dermatologist. Any use, re-creation, dissemination, forwarding or copying of this ...

  20. Arm MRI scan

    MedlinePlus

    ... MRI and often available in the emergency room. Alternative Names MRI - arm; Wrist MRI; MRI - wrist; Elbow ... any medical emergency or for the diagnosis or treatment of any medical condition. A licensed physician should ...

  1. Look at my Arms!

    NASA Image and Video Library

    2005-07-25

    This image shows the hidden spiral arms that were discovered around the galaxy called NGC 4625 top by the ultraviolet eyes of NASA Galaxy Evolution Explorer. An armless companion galaxy called NGC 4618 is pictured below.

  2. Phoenix Robotic Arm Rasp

    NASA Image and Video Library

    2008-07-15

    This photograph shows the rasp protruding from the back of the scoop on NASA Phoenix Mars Lander Robotic Arm engineering model in the Payload Interoperability Testbed at the University of Arizona, Tucson.

  3. Worldwide Report, Arms Control

    DTIC Science & Technology

    1985-12-19

    disarmament shows that the decisive factor in Soviet-U.S. relations remains the sphere of security, the core of which is the organically linked ...actiye in the United States for whom the very prospect of preconditions for curbing the arms race is patently not to their linking . Certain quarters in...distorting the essence of the issue of the organic link between preventing the mili- tarization of space and the reduction of nuclear arms on earth

  4. Arms Control Fellowship

    NASA Astrophysics Data System (ADS)

    The U.S. Arms Control and Disarmament Agency (ACDA) has announced that it is accepting applications for visiting scholars under the William C. Foster Fellows Program for 1986-1987. This program is designed to give specialists in the physical sciences and other disciplines relevant to ACDA activities an opportunity to participate actively in the arms control and disarmament activities of this agency and to give ACDA the perspective and expertise that such people can offer.

  5. Dynein-Dependent Transport of the Hantaan Virus Nucleocapsid Protein to the Endoplasmic Reticulum-Golgi Intermediate Compartment▿

    PubMed Central

    Ramanathan, Harish N.; Chung, Dong-Hoon; Plane, Steven J.; Sztul, Elizabeth; Chu, Yong-kyu; Guttieri, Mary C.; McDowell, Michael; Ali, Georgia; Jonsson, Colleen B.

    2007-01-01

    In contrast to most negative-stranded RNA viruses, hantaviruses and other viruses in the family Bunyaviridae mature intracellularly, deriving the virion envelope from the endoplasmic reticulum (ER) or Golgi compartment. While it is generally accepted that Old World hantaviruses assemble and bud into the Golgi compartment, some studies with New World hantaviruses have raised the possibility of maturation at the plasma membrane as well. Overall, the steps leading to virion assembly remain largely undetermined for hantaviruses. Because hantaviruses do not have matrix proteins, the nucleocapsid protein (N) has been proposed to play a key role in assembly. Herein, we examine the intracellular trafficking and morphogenesis of the prototype Old World hantavirus, Hantaan virus (HTNV). Using confocal microscopy, we show that N colocalized with the ER-Golgi intermediate compartment (ERGIC) in HTNV-infected Vero E6 cells, not with the ER, Golgi compartment, or early endosomes. Brefeldin A, which effectively disperses the ER, the ERGIC, and Golgi membranes, redistributed N with the ERGIC, implicating membrane association; however, subcellular fractionation experiments showed the majority of N in particulate fractions. Confocal microscopy revealed that N was juxtaposed to and distributed along microtubules and, over time, became surrounded by vimentin cages. To probe cytoskeletal association further, we probed trafficking of N in cells treated with nocodazole and cytochalasin D, which depolymerize microtubules and actin, respectively. We show that nocodazole, but not cytochalasin D, affected the distribution of N and reduced levels of intracellular viral RNA. These results suggested the involvement of microtubules in trafficking of N, whose movement could occur via molecular motors such as dynein. Overexpression of dynamitin, which is associated with dynein-mediated transport, creates a dominant-negative phenotype blocking transport on microtubules. Overexpression of dynamitin

  6. Hello to Arms

    NASA Technical Reports Server (NTRS)

    2005-01-01

    This image highlights the hidden spiral arms (blue) that were discovered around the nearby galaxy NGC 4625 by the ultraviolet eyes of NASA's Galaxy Evolution Explorer.

    The image is composed of ultraviolet and visible-light data, from the Galaxy Evolution Explorer and the California Institute of Technology's Digitized Sky Survey, respectively. Near-ultraviolet light is colored green; far-ultraviolet light is colored blue; and optical light is colored red.

    As the image demonstrates, the lengthy spiral arms are nearly invisible when viewed in optical light while bright in ultraviolet. This is because they are bustling with hot, newborn stars that radiate primarily ultraviolet light.

    The youthful arms are also very long, stretching out to a distance four times the size of the galaxy's core. They are part of the largest ultraviolet galactic disk discovered so far.

    Located 31 million light-years away in the constellation Canes Venatici, NGC 4625 is the closest galaxy ever seen with such a young halo of arms. It is slightly smaller than our Milky Way, both in size and mass. However, the fact that this galaxy's disk is forming stars very actively suggests that it might evolve into a more massive and mature galaxy resembling our own.

    The armless companion galaxy seen below NGC 4625 is called NGC 4618. Astronomers do not know why it lacks arms but speculate that it may have triggered the development of arms in NGC 4625.

  7. Consecutive learning of opposing unimanual motor tasks using the right arm followed by the left arm causes intermanual interference

    PubMed Central

    Thürer, Benjamin; Stein, Thorsten

    2017-01-01

    Intermanual transfer (motor memory generalization across arms) and motor memory interference (impairment of retest performance in consecutive motor learning) are well-investigated motor learning phenomena. However, the interplay of these phenomena remains elusive, i.e., whether intermanual interference occurs when two unimanual tasks are consecutively learned using different arms. Here, we examine intermanual interference when subjects consecutively adapt their right and left arm movements to novel dynamics. We considered two force field tasks A and B which were of the same structure but mirrored orientation (B = -A). The first test group (ABA-group) consecutively learned task A using their right arm and task B using their left arm before being retested for task A with their right arm. Another test group (AAA-group) learned only task A in the same right-left-right arm schedule. Control subjects learned task A using their right arm without intermediate left arm learning. All groups were able to adapt their right arm movements to force field A and both test groups showed significant intermanual transfer of this initial learning to the contralateral left arm of 21.9% (ABA-group) and 27.6% (AAA-group). Consecutively, both test groups adapted their left arm movements to force field B (ABA-group) or force field A (AAA-group). For the ABA-group, left arm learning caused significant intermanual interference of the initially learned right arm task (68.3% performance decrease). The performance decrease of the AAA-group (10.2%) did not differ from controls (15.5%). These findings suggest that motor control and learning of right and left arm movements involve partly similar neural networks or underlie a vital interhemispheric connectivity. Moreover, our results suggest a preferred internal task representation in extrinsic Cartesian-based coordinates rather than in intrinsic joint-based coordinates because interference was absent when learning was performed in extrinsically

  8. Consecutive learning of opposing unimanual motor tasks using the right arm followed by the left arm causes intermanual interference.

    PubMed

    Stockinger, Christian; Thürer, Benjamin; Stein, Thorsten

    2017-01-01

    Intermanual transfer (motor memory generalization across arms) and motor memory interference (impairment of retest performance in consecutive motor learning) are well-investigated motor learning phenomena. However, the interplay of these phenomena remains elusive, i.e., whether intermanual interference occurs when two unimanual tasks are consecutively learned using different arms. Here, we examine intermanual interference when subjects consecutively adapt their right and left arm movements to novel dynamics. We considered two force field tasks A and B which were of the same structure but mirrored orientation (B = -A). The first test group (ABA-group) consecutively learned task A using their right arm and task B using their left arm before being retested for task A with their right arm. Another test group (AAA-group) learned only task A in the same right-left-right arm schedule. Control subjects learned task A using their right arm without intermediate left arm learning. All groups were able to adapt their right arm movements to force field A and both test groups showed significant intermanual transfer of this initial learning to the contralateral left arm of 21.9% (ABA-group) and 27.6% (AAA-group). Consecutively, both test groups adapted their left arm movements to force field B (ABA-group) or force field A (AAA-group). For the ABA-group, left arm learning caused significant intermanual interference of the initially learned right arm task (68.3% performance decrease). The performance decrease of the AAA-group (10.2%) did not differ from controls (15.5%). These findings suggest that motor control and learning of right and left arm movements involve partly similar neural networks or underlie a vital interhemispheric connectivity. Moreover, our results suggest a preferred internal task representation in extrinsic Cartesian-based coordinates rather than in intrinsic joint-based coordinates because interference was absent when learning was performed in extrinsically

  9. Kinematically redundant arm formulations for coordinated multiple arm implementations

    NASA Technical Reports Server (NTRS)

    Bailey, Robert W.; Quiocho, Leslie J.; Cleghorn, Timothy F.

    1990-01-01

    Although control laws for kinematically redundant robotic arms were presented as early as 1969, redundant arms have only recently become recognized as viable solutions to limitations inherent to kinematically sufficient arms. The advantages of run-time control optimization and arm reconfiguration are becoming increasingly attractive as the complexity and criticality of robotic systems continues to progress. A generalized control law for a spatial arm with 7 or more degrees of freedom (DOF) based on Whitney's resolved rate formulation is given. Results from a simulation implementation utilizing this control law are presented. Furthermore, results from a two arm simulation are presented to demonstrate the coordinated control of multiple arms using this formulation.

  10. LC3 binding to the scaffolding protein JIP1 regulates processive dynein-driven transport of autophagosomes.

    PubMed

    Fu, Meng-Meng; Nirschl, Jeffrey J; Holzbaur, Erika L F

    2014-06-09

    Autophagy is essential for maintaining cellular homeostasis in neurons, where autophagosomes undergo robust unidirectional retrograde transport along axons. We find that the motor scaffolding protein JIP1 binds directly to the autophagosome adaptor LC3 via a conserved LIR motif. This interaction is required for the initial exit of autophagosomes from the distal axon, for sustained retrograde transport along the midaxon, and for autophagosomal maturation in the proximal axon. JIP1 binds directly to the dynein activator dynactin but also binds to and activates kinesin-1 in a phosphorylation-dependent manner. Following JIP1 depletion, phosphodeficient JIP1-S421A rescues retrograde transport, while phosphomimetic JIP1-S421D aberrantly activates anterograde transport. During normal autophagosome transport, residue S421 of JIP1 may be maintained in a dephosphorylated state by autophagosome-associated MKP1 phosphatase. Moreover, binding of LC3 to JIP1 competitively disrupts JIP1-mediated activation of kinesin. Thus, dual mechanisms prevent aberrant activation of kinesin to ensure robust retrograde transport of autophagosomes along the axon. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Dynein light chain 1 induces assembly of large Bim complexes on mitochondria that stabilize Mcl-1 and regulate apoptosis

    PubMed Central

    Singh, Prafull Kumar; Roukounakis, Aristomenis; Frank, Daniel O.; Kirschnek, Susanne; Das, Kushal Kumar; Neumann, Simon; Madl, Josef; Römer, Winfried; Zorzin, Carina; Borner, Christoph; Haimovici, Aladin; Garcia-Saez, Ana; Weber, Arnim; Häcker, Georg

    2017-01-01

    The Bcl-2 family protein Bim triggers mitochondrial apoptosis. Bim is expressed in nonapoptotic cells at the mitochondrial outer membrane, where it is activated by largely unknown mechanisms. We found that Bim is regulated by formation of large protein complexes containing dynein light chain 1 (DLC1). Bim rapidly inserted into cardiolipin-containing membranes in vitro and recruited DLC1 to the membrane. Bim binding to DLC1 induced the formation of large Bim complexes on lipid vesicles, on isolated mitochondria, and in intact cells. Native gel electrophoresis and gel filtration showed Bim-containing mitochondrial complexes of several hundred kilodaltons in all cells tested. Bim unable to form complexes was consistently more active than complexed Bim, which correlated with its substantially reduced binding to anti-apoptotic Bcl-2 proteins. At endogenous levels, Bim surprisingly bound only anti-apoptotic Mcl-1 but not Bcl-2 or Bcl-XL, recruiting only Mcl-1 into large complexes. Targeting of DLC1 by RNAi in human cell lines induced disassembly of Bim–Mcl-1 complexes and the proteasomal degradation of Mcl-1 and sensitized the cells to the Bcl-2/Bcl-XL inhibitor ABT-737. Regulation of apoptosis at mitochondria thus extends beyond the interaction of monomers of proapoptotic and anti-apoptotic Bcl-2 family members but involves more complex structures of proteins at the mitochondrial outer membrane, and targeting complexes may be a novel therapeutic strategy. PMID:28982759

  12. Dynein-Dependent Transport of nanos RNA in Drosophila Sensory Neurons Requires Rumpelstiltskin and the Germ Plasm Organizer Oskar

    PubMed Central

    Xu, Xin; Brechbiel, Jillian L.

    2013-01-01

    Intracellular mRNA localization is a conserved mechanism for spatially regulating protein production in polarized cells, such as neurons. The mRNA encoding the translational repressor Nanos (Nos) forms ribonucleoprotein (RNP) particles that are dendritically localized in Drosophila larval class IV dendritic arborization (da) neurons. In nos mutants, class IV da neurons exhibit reduced dendritic branching complexity, which is rescued by transgenic expression of wild-type nos mRNA but not by a localization-compromised nos derivative. While localization is essential for nos function in dendrite morphogenesis, the mechanism underlying the transport of nos RNP particles was unknown. We investigated the mechanism of dendritic nos mRNA localization by analyzing requirements for nos RNP particle motility in class IV da neuron dendrites through live imaging of fluorescently labeled nos mRNA. We show that dynein motor machinery components mediate transport of nos mRNA in proximal dendrites. Two factors, the RNA-binding protein Rumpelstiltskin and the germ plasm protein Oskar, which are required for diffusion/entrapment-mediated localization of nos during oogenesis, also function in da neurons for formation and transport of nos RNP particles. Additionally, we show that nos regulates neuronal function, most likely independent of its dendritic localization and function in morphogenesis. Our results reveal adaptability of localization factors for regulation of a target transcript in different cellular contexts. PMID:24027279

  13. Dynein-dependent transport of nanos RNA in Drosophila sensory neurons requires Rumpelstiltskin and the germ plasm organizer Oskar.

    PubMed

    Xu, Xin; Brechbiel, Jillian L; Gavis, Elizabeth R

    2013-09-11

    Intracellular mRNA localization is a conserved mechanism for spatially regulating protein production in polarized cells, such as neurons. The mRNA encoding the translational repressor Nanos (Nos) forms ribonucleoprotein (RNP) particles that are dendritically localized in Drosophila larval class IV dendritic arborization (da) neurons. In nos mutants, class IV da neurons exhibit reduced dendritic branching complexity, which is rescued by transgenic expression of wild-type nos mRNA but not by a localization-compromised nos derivative. While localization is essential for nos function in dendrite morphogenesis, the mechanism underlying the transport of nos RNP particles was unknown. We investigated the mechanism of dendritic nos mRNA localization by analyzing requirements for nos RNP particle motility in class IV da neuron dendrites through live imaging of fluorescently labeled nos mRNA. We show that dynein motor machinery components mediate transport of nos mRNA in proximal dendrites. Two factors, the RNA-binding protein Rumpelstiltskin and the germ plasm protein Oskar, which are required for diffusion/entrapment-mediated localization of nos during oogenesis, also function in da neurons for formation and transport of nos RNP particles. Additionally, we show that nos regulates neuronal function, most likely independent of its dendritic localization and function in morphogenesis. Our results reveal adaptability of localization factors for regulation of a target transcript in different cellular contexts.

  14. A subunit of the dynein regulatory complex in Chlamydomonas is a homologue of a growth arrest–specific gene product

    PubMed Central

    Rupp, Gerald; Porter, Mary E.

    2003-01-01

    The dynein regulatory complex (DRC) is an important intermediate in the pathway that regulates flagellar motility. To identify subunits of the DRC, we characterized a Chlamydomonas motility mutant obtained by insertional mutagenesis. The pf2-4 mutant displays an altered waveform that results in slow swimming cells. EM analysis reveals defects in DRC structure that can be rescued by reintroduction of the wild-type PF2 gene. Immunolocalization studies show that the PF2 protein is distributed along the length of the axoneme, where it is part of a discrete complex of polypeptides. PF2 is a coiled-coil protein that shares significant homology with a mammalian growth arrest–specific gene product (Gas11/Gas8) and a trypanosome protein known as trypanin. PF2 and its homologues appear to be universal components of motile axonemes that are required for DRC assembly and the regulation of flagellar motility. The expression of Gas8/Gas11 transcripts in a wide range of tissues may also indicate a potential role for PF2-related proteins in other microtubule-based structures. PMID:12847082

  15. Dynein light chain 1 induces assembly of large Bim complexes on mitochondria that stabilize Mcl-1 and regulate apoptosis.

    PubMed

    Singh, Prafull Kumar; Roukounakis, Aristomenis; Frank, Daniel O; Kirschnek, Susanne; Das, Kushal Kumar; Neumann, Simon; Madl, Josef; Römer, Winfried; Zorzin, Carina; Borner, Christoph; Haimovici, Aladin; Garcia-Saez, Ana; Weber, Arnim; Häcker, Georg

    2017-09-01

    The Bcl-2 family protein Bim triggers mitochondrial apoptosis. Bim is expressed in nonapoptotic cells at the mitochondrial outer membrane, where it is activated by largely unknown mechanisms. We found that Bim is regulated by formation of large protein complexes containing dynein light chain 1 (DLC1). Bim rapidly inserted into cardiolipin-containing membranes in vitro and recruited DLC1 to the membrane. Bim binding to DLC1 induced the formation of large Bim complexes on lipid vesicles, on isolated mitochondria, and in intact cells. Native gel electrophoresis and gel filtration showed Bim-containing mitochondrial complexes of several hundred kilodaltons in all cells tested. Bim unable to form complexes was consistently more active than complexed Bim, which correlated with its substantially reduced binding to anti-apoptotic Bcl-2 proteins. At endogenous levels, Bim surprisingly bound only anti-apoptotic Mcl-1 but not Bcl-2 or Bcl-X L , recruiting only Mcl-1 into large complexes. Targeting of DLC1 by RNAi in human cell lines induced disassembly of Bim-Mcl-1 complexes and the proteasomal degradation of Mcl-1 and sensitized the cells to the Bcl-2/Bcl-X L inhibitor ABT-737. Regulation of apoptosis at mitochondria thus extends beyond the interaction of monomers of proapoptotic and anti-apoptotic Bcl-2 family members but involves more complex structures of proteins at the mitochondrial outer membrane, and targeting complexes may be a novel therapeutic strategy. © 2017 Singh et al.; Published by Cold Spring Harbor Laboratory Press.

  16. Computer interface for mechanical arm

    NASA Technical Reports Server (NTRS)

    Derocher, W. L.; Zermuehlen, R. O.

    1978-01-01

    Man/machine interface commands computer-controlled mechanical arm. Remotely-controlled arm has six degrees of freedom and is controlled through "supervisory-control" mode, in which all motions of arm follow set of preprogramed sequences. For simplicity, few prescribed commands are required to accomplish entire operation. Applications include operating computer-controlled arm to handle radioactive of explosive materials or commanding arm to perform functions in hostile environments. Modified version using displays may be applied in medicine.

  17. Armed conflict and child health.

    PubMed

    Rieder, Michael; Choonara, Imti

    2012-01-01

    Armed conflict has a major impact on child health throughout the world. One in six children worldwide lives in an area of armed conflict and civilians are more likely to die than soldiers as a result of the conflict. In stark contrast to the effect on children, the international arms trade results in huge profits for the large corporations involved in producing arms, weapons and munitions. Armed conflict is not inevitable but is an important health issue that should be prevented.

  18. Robotic Arm Unwrapped

    NASA Technical Reports Server (NTRS)

    2008-01-01

    This image, taken shortly after NASA's Phoenix Mars Lander touched down on the surface of Mars, shows the spacecraft's robotic arm in its stowed configuration, with its biobarrier successfully unpeeled. The 'elbow' of the arm can be seen at the top center of the picture, and the biobarrier is the shiny film seen to the left of the arm.

    The biobarrier is an extra precautionary measure for protecting Mars from contamination with any bacteria from Earth. While the whole spacecraft was decontaminated through cleaning, filters and heat, the robotic arm was given additional protection because it is the only spacecraft part that will directly touch the ice below the surface of Mars.

    Before the arm was heated, it was sealed in the biobarrier, which is made of a trademarked film called Tedlar that holds up to baking like a turkey-basting bag. This ensures that any new bacterial spores that might have appeared during the final steps before launch and during the journey to Mars will not contact the robotic arm.

    After Phoenix landed, springs were used to pop back the barrier, giving it room to deploy.

    The base of the lander's Meteorological Station can be seen in this picture on the upper left. Because only the base of the station is showing, this image tells engineers that the instrument deployed successfully.

    The image was taken on landing day, May 25, 2008, by the spacecraft's Surface Stereo Imager.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  19. Worldwide Report, Arms Control.

    DTIC Science & Technology

    1985-07-19

    on measures of substantially reducing medium -range nuclear arms to agreed-upon levels on the basis of reciprocity and in strict conformity with the ...to the United States to reach agreement on the immediate discontinua- tion by the United States of the deployment of medium -range missiles in Europe... by unilaterally imposing a moratorium on the

  20. Flexing Curiosity's Arm

    NASA Image and Video Library

    2012-09-06

    This engineering drawing shows the arm on NASA's Curiosity's rover in its "ready-for-action" position, or "ready out" as engineers say, in addition to the position it assumes to drop off samples. http://photojournal.jpl.nasa.gov/catalog/PIA16147

  1. Worldwide Report, Arms Control

    DTIC Science & Technology

    1986-02-28

    NACHRICHTEN , 18 Oct 85) 39 Presummit Polish Reporting on SDI Issues (Warsaw RZECZPOSPOLITA, 19-20 Oct 85; Warsaw ZYCIE WARSZAWY, 15 Oct 85) 42...28 February 1986 SDI AND SPACE ARMS MEETING REVEALS SOME SUPPORT FOR EUREKA LINK TO MILITARY Puesseldbrf VDI NACHRICHTEN in German 18 Oct 85 p 10

  2. Clinical Characteristics and Associated Systemic Diseases in Patients With Esophageal "Absent Contractility"-A Clinical Algorithm.

    PubMed

    Laique, Sobia; Singh, Tavankit; Dornblaser, David; Gadre, Abhishek; Rangan, Vikram; Fass, Ronnie; Kirby, Donald; Chatterjee, Soumya; Gabbard, Scott

    2018-01-19

    This study was carried out to assess the clinical characteristics and associated systemic diseases seen in patients diagnosed with absent contractility as per the Chicago Classification version 3.0, allowing us to propose a diagnostic algorithm for their etiologic testing. The Chicago Classification version 3.0 has redefined major and minor esophageal motility disorders using high-resolution esophageal manometry. There is a dearth of publications based on research on absent contractility, which historically has been associated with myopathic processes such as systemic sclerosis (SSc). We conducted a retrospective, multicenter study. Data of patients diagnosed with absent contractility were pooled from Cleveland Clinic, Cleveland, OH (January 2006 to July 2016) and Metrohealth Medical Center, Cleveland, OH (July 2014 to July 2016) and included: age, gender, associated medical conditions, surgical history, medications, and specific antibody testing. A total of 207 patients, including 57 male individuals and 150 female individuals, with mean age of 56.1 and 60.0 years, respectively, were included. Disease distribution was as follows: SSc (diffuse or limited cutaneous) 132, overlap syndromes 7, systemic lupus erythematosus17, Sjögren syndrome 4, polymyositis 3, and dermatomyositis 3. Various other etiologies including gastroesophageal reflux disease, postradiation esophagitis, neuromuscular disorders, and surgical complications were seen in the remaining cohort. Most practitioners use the term "absent contractility" interchangeably with "scleroderma esophagus"; however, only 63% of patients with absent contractility had SSc. Overall, 20% had another systemic autoimmune rheumatologic disease and 16% had a nonrheumatologic etiology for absent contractility. Therefore, alternate diagnosis must be sought in these patients. We propose an algorithm for their etiologic evaluation.

  3. Coordination of multiple robot arms

    NASA Technical Reports Server (NTRS)

    Barker, L. K.; Soloway, D.

    1987-01-01

    Kinematic resolved-rate control from one robot arm is extended to the coordinated control of multiple robot arms in the movement of an object. The structure supports the general movement of one axis system (moving reference frame) with respect to another axis system (control reference frame) by one or more robot arms. The grippers of the robot arms do not have to be parallel or at any pre-disposed positions on the object. For multiarm control, the operator chooses the same moving and control reference frames for each of the robot arms. Consequently, each arm then moves as though it were carrying out the commanded motions by itself.

  4. Structure of a Yeast Dyn2-Nup159 Complex and Molecular Basis for Dynein Light Chain-Nuclear Pore Interaction*

    PubMed Central

    Romes, Erin M.; Tripathy, Ashutosh; Slep, Kevin C.

    2012-01-01

    The nuclear pore complex gates nucleocytoplasmic transport through a massive, eight-fold symmetric channel capped by a nucleoplasmic basket and structurally unique, cytoplasmic fibrils whose tentacles bind and regulate asymmetric traffic. The conserved Nup82 complex, composed of Nsp1, Nup82, and Nup159, forms the unique cytoplasmic fibrils that regulate mRNA nuclear export. Although the nuclear pore complex plays a fundamental, conserved role in nuclear trafficking, structural information about the cytoplasmic fibrils is limited. Here, we investigate the structural and biochemical interactions between Saccharomyces cerevisiae Nup159 and the nucleoporin, Dyn2. We find that Dyn2 is predominantly a homodimer and binds arrayed sites on Nup159, promoting the Nup159 parallel homodimerization. We present the first structure of Dyn2, determined at 1.85 Å resolution, complexed with a Nup159 target peptide. Dyn2 resembles homologous metazoan dynein light chains, forming homodimeric composite substrate binding sites that engage two independent 10-residue target motifs, imparting a β-strand structure to each peptide via antiparallel extension of the Dyn2 core β-sandwich. Dyn2 recognizes a highly conserved QT motif while allowing sequence plasticity in the flanking residues of the peptide. Isothermal titration calorimetric analysis of the comparative binding of Dyn2 to two Nup159 target sites shows similar affinities (18 and 13 μm), but divergent thermal binding modes. Dyn2 homodimers are arrayed in the crystal lattice, likely mimicking the arrayed architecture of Dyn2 on the Nup159 multivalent binding sites. Crystallographic interdimer interactions potentially reflect a cooperative basis for Dyn2-Nup159 complex formation. Our data highlight the determinants that mediate oligomerization of the Nup82 complex and promote a directed, elongated cytoplasmic fibril architecture. PMID:22411995

  5. The counterbend phenomenon in dynein-disabled rat sperm flagella and what it reveals about the interdoublet elasticity.

    PubMed

    Lindemann, Charles B; Macauley, Lisa J; Lesich, Kathleen A

    2005-08-01

    Rat sperm that have been rendered passive by disabling the dynein motors with 50 muM sodium metavanadate and 0.1 mM ATP exhibit an interesting response to imposed bending. When the proximal flagellum is bent with a microprobe, the portion of the flagellum distal to the probe contact point develops a bend in the direction opposite the imposed bend. This "counterbend" is not compatible with a simple elastic beam. It can be satisfactorily explained by the sliding tubule model of flagellar structure but only if there are permanent elastic connections between the outer doublets of the axoneme. The elastic component that contributes the bending torque for the counterbend does not reset to a new equilibrium position after an imposed bend but returns the flagellum to a nearly straight or slightly curved final position after release from the probe. This suggests it is based on fixed, rather than mobile, attachments. It is also disrupted by elastase or trypsin digestion, confirming that it is dependent on a protein linkage. Adopting the assumption that the elasticity is attributed to the nexin links that repeat at 96 nm intervals, we find an apparent elasticity for each link that ranges from 1.6 to 10 x 10(-5) N/m. However, the elasticity is nonlinear and does not follow Hooke's law but appears to decrease with increased stretch. In addition, the responsible elastic elements must be able to stretch to more than 10 times their resting length without breakage to account for the observed counterbend formation. Elasticity created by some type of protein unfolding may be the only viable explanation consistent with both the extreme capacity for extension and the nonlinear character of the restoring force that is observed.

  6. The Counterbend Phenomenon in Dynein-Disabled Rat Sperm Flagella and What It Reveals about the Interdoublet Elasticity

    PubMed Central

    Lindemann, Charles B.; Macauley, Lisa J.; Lesich, Kathleen A.

    2005-01-01

    Rat sperm that have been rendered passive by disabling the dynein motors with 50 μM sodium metavanadate and 0.1 mM ATP exhibit an interesting response to imposed bending. When the proximal flagellum is bent with a microprobe, the portion of the flagellum distal to the probe contact point develops a bend in the direction opposite the imposed bend. This “counterbend” is not compatible with a simple elastic beam. It can be satisfactorily explained by the sliding tubule model of flagellar structure but only if there are permanent elastic connections between the outer doublets of the axoneme. The elastic component that contributes the bending torque for the counterbend does not reset to a new equilibrium position after an imposed bend but returns the flagellum to a nearly straight or slightly curved final position after release from the probe. This suggests it is based on fixed, rather than mobile, attachments. It is also disrupted by elastase or trypsin digestion, confirming that it is dependent on a protein linkage. Adopting the assumption that the elasticity is attributed to the nexin links that repeat at 96 nm intervals, we find an apparent elasticity for each link that ranges from 1.6 to 10 × 10−5 N/m. However, the elasticity is nonlinear and does not follow Hooke's law but appears to decrease with increased stretch. In addition, the responsible elastic elements must be able to stretch to more than 10 times their resting length without breakage to account for the observed counterbend formation. Elasticity created by some type of protein unfolding may be the only viable explanation consistent with both the extreme capacity for extension and the nonlinear character of the restoring force that is observed. PMID:15923232

  7. When Familiar Is Not Better: 12-Month-Old Infants Respond to Talk about Absent Objects

    ERIC Educational Resources Information Center

    Osina, Maria A.; Saylor, Megan M.; Ganea, Patricia A.

    2013-01-01

    Three experiments that demonstrate a novel constraint on infants' language skills are described. Across the experiments it is shown that as babies near their 1st birthday, their ability to respond to talk about an absent object is influenced by a referent's spatiotemporal history: familiarizing infants with an object in 1 or several nontest…

  8. Does Research on Children Reared in Father-absent Families Yield Information on Father Influences?

    ERIC Educational Resources Information Center

    Pedersen, Frank A.

    1976-01-01

    The most frequently employed research design for studying paternal influences on child development has been to compare children reared in father-absent families to those reared in father-present families. Research should be directed to the study and conceptualization of the more specific components of experience in the father-child and…

  9. Fourteen-Month-Olds' Decontextualized Understanding of Words for Absent Objects

    ERIC Educational Resources Information Center

    Hendrickson, Kristi; Sundara, Megha

    2017-01-01

    The majority of research examining infants' decontextualized word knowledge comes from studies in which words and pictures are presented simultaneously. However, comprehending utterances about unseen objects is a hallmark of language. Do infants demonstrate decontextualized absent object knowledge early in the second year of life? Further, to what…

  10. Equality, Difference and the Absent Presence of "Race" in Citizenship Education in the UK

    ERIC Educational Resources Information Center

    Garratt, Dean

    2011-01-01

    This paper examines the political and historical antecedents of the absent presence of "race" in successive policies for citizenship education in contemporary Britain. It questions the possibility of embracing an emerging cosmopolitanism and politics of difference, within the limiting frame of the nation state and its overarching appeal…

  11. Understanding the conventional arms trade

    NASA Astrophysics Data System (ADS)

    Stohl, Rachel

    2017-11-01

    The global conventional arms trade is worth tens of billions of dollars every year and is engaged in by every country in the world. Yet, it is often difficult to control the legal trade in conventional arms and there is a thriving illicit market, willing to arm unscrupulous regimes and nefarious non-state actors. This chapter examines the international conventional arms trade, the range of tools that have been used to control it, and challenges to these international regimes.

  12. Microelectromechanical safe arm device

    DOEpatents

    Roesler, Alexander W [Tijeras, NM

    2012-06-05

    Microelectromechanical (MEM) apparatus and methods for operating, for preventing unintentional detonation of energetic components comprising pyrotechnic and explosive materials, such as air bag deployment systems, munitions and pyrotechnics. The MEM apparatus comprises an interrupting member that can be moved to block (interrupt) or complete (uninterrupt) an explosive train that is part of an energetic component. One or more latching members are provided that engage and prevent the movement of the interrupting member, until the one or more latching members are disengaged from the interrupting member. The MEM apparatus can be utilized as a safe and arm device (SAD) and electronic safe and arm device (ESAD) in preventing unintentional detonations. Methods for operating the MEM apparatus include independently applying drive signals to the actuators coupled to the latching members, and an actuator coupled to the interrupting member.

  13. Robot arm apparatus

    DOEpatents

    Nachbar, Henry D.

    1992-12-01

    A robot arm apparatus is provided for inspecting and/or maintaining an interior of a steam generator which has an outside wall and a port for accessing the interior of the steam generator. The robot arm apparatus includes a flexible movable conduit for conveying inspection and/or maintenance apparatus from outside the steam generator to the interior of the steam generator. The flexible conduit has a terminal working end which is translated into and around the interior of the steam generator. Three motors located outside the steam generator are employed for moving the terminal working end inside the steam generator in "x", "y", and "z" directions, respectively. Commonly conducted inspection and maintenance operations include visual inspection for damaged areas, water jet lancing for cleaning sludge deposits, core boring for obtaining sludge deposits, and scrubbing of internal parts.

  14. Robot arm apparatus

    DOEpatents

    Nachbar, Henry D.

    1992-01-01

    A robot arm apparatus is provided for inspecting and/or maintaining an interior of a steam generator which has an outside wall and a port for accessing the interior of the steam generator. The robot arm apparatus includes a flexible movable conduit for conveying inspection and/or maintenance apparatus from outside the steam generator to the interior of the steam generator. The flexible conduit has a terminal working end which is translated into and around the interior of the steam generator. Three motors located outside the steam generator are employed for moving the terminal working end inside the steam generator in "x", "y", and "z" directions, respectively. Commonly conducted inspection and maintenance operations include visual inspection for damaged areas, water jet lancing for cleaning sludge deposits, core boring for obtaining sludge deposits, and scrubbing of internal parts.

  15. Worldwide Report, Arms Control.

    DTIC Science & Technology

    1985-11-06

    Second Edition p 3 [Commentary by TASS military observer V. Chernyshev: "A Turbid Stream From Washington"] [Text] The more practical steps and...space strike arms and put its "star wars" program into practice . Take, for instance, the foreword to the pamphlet, signed by Defense Secretary C...American empire." According to the American press, the completed "Discovery" flight represented one more practical step in the realization of the so

  16. Worldwide Report, Arms Control.

    DTIC Science & Technology

    1985-06-13

    283086 JPRS-TAC-85-0 12 13 June 1985 Worldwide Report ARMS CONTROL 19980729 131 — . „_ | ^^CQWArpmr Approved fa pnbfi* nümam...retained. Headlines, editorial reports , and material enclosed in brackets [] are supplied by JPRS. Processing indicators such as [Text] or...JPRS number, title, date and author, if applicable, of publication be cited. Current JPRS publications are announced in Government Reports

  17. Small arms ammunition

    DOEpatents

    Huerta, Joseph

    1992-01-01

    An elongate projectile for small arms use has a single unitary mass with a hollow nose cavity defined by a sharp rigid cutting edge adapted to make initial contact with the target surface and cut therethrough. The projectile then enters the target mass in an unstable flight mode. The projectile base is substantially solid such that the nose cavity, while relatively deep, does not extend entirely through the base and the projectile center of gravity is aft of its geometric center.

  18. JPRS Report, Arms Control

    DTIC Science & Technology

    1989-11-13

    manufacturing or using beam facilities. Radiation signs and necessary protection security interlocking mechanisms, alarm systems, or signals must be...JPRS-TAC-89-037 13 NOVEMBER 1989 JPRS tit Arms Control 715 159 REPRODUCED BY US DEPARTMENT OF COMMERCE NATIONAL TECHNICAL INFORMATION SERVICE...Xue Ren; J1EFANGJUN BAO 20 Oct] 4 Li Peng Signs Radiation Protection Decree [XINHUA 1 Nov] 5 Nuclear Technology Applied to Nonmilitary Use

  19. Armed Forces Food Preferences

    DTIC Science & Technology

    1974-12-01

    Breakfast Cereals 11 Griddle Cakes 12 Eggs 13 Breakfast Meats Arm®d Forces High Preference and Low Preference Foods HIGH Tom. Veg. Noodle Soup...Tomato Soup Chicken Noodle Soup Orange Juice Grape Juice Lemonade Iced Tea Milk Ice Cream Cola Doughnuts Sweet Rolls Cold Cereal Griddle...Grape Lemonade Lime-Flavored Drink Cherry-Flavored Drink Instant Coffee Freeze-Dried Coffee Skimmed Milk Buttermilk Frutt-Flvd. Yogurt Lo-cal

  20. Scientific coats of arms.

    PubMed

    Fara, Patricia

    2005-09-01

    With their mythical creatures and arcane symbolism, coats of arms seem to have little connection with modern science. Yet despite its chivalric origins, the ancient language of heraldry has long fascinated famous scientists. Although this idiosyncratic tradition was parodied by Victorian geologists, who laughingly replaced unicorns and griffins with images of dinosaurs that they had recently discovered, it has been perpetuated since by Ernest Rutherford, who liked to present himself as a new alchemist.

  1. Worldwide Report, Arms Control

    DTIC Science & Technology

    1985-08-19

    Ignatiev reports: posal on the nuclear arms freeze. Spring at a press conference herd ^^S"^^^^^ fitted that a draft la» on in„educing a »rate...These pseudopeaceloving proposals are nothing more than mimicry and a diversionary maneuver undertaken in the face of the specific and important...their stay in Moscow the delegation members visited the 50-Letiya SSSR Auto- mated Flowing Plant , where they were shown the organization of the

  2. Worldwide Report, Arms Control.

    DTIC Science & Technology

    1985-11-22

    dinosaurs (and a large number of other species which disappeared "simultaneously") might have become extinct because a large comet hit the earth’s...clear yet aeain the reasons why Washington is in such haste in the arms race for "star wars" and why it refuses to assume a commitment not to be...Kolesnichenko says: [Begin Kolesnichenko recording in Russian with English translation] In an effort to calm the American public and provide a logical reason

  3. Phoenix Robotic Arm

    NASA Technical Reports Server (NTRS)

    2007-01-01

    A vital instrument on NASA's Phoenix Mars Lander is the robotic arm, which will dig into the icy soil and bring samples back to the science deck of the spacecraft for analysis. In September 2006 at a Lockheed Martin Space Systems clean room facility near Denver, spacecraft technician Billy Jones inspects the arm during the assembly phase of the mission.

    Using the robotic arm -- built by the Jet Propulsion Laboratory, Pasadena -- the Phoenix mission will study the history of water and search for complex organic molecules in the ice-rich soil.

    The Phoenix mission is led by Principal Investigator Peter H. Smith of the University of Arizona, Tucson, with project management at NASA's Jet Propulsion Laboratory and development partnership with Lockheed Martin Space Systems. International contributions for Phoenix are provided by the Canadian Space Agency, the University of Neuchatel (Switzerland), the University of Copenhagen, and the Max Planck Institute in Germany. JPL is a division of the California Institute of Technology in Pasadena.

  4. A novel mouse model carrying a human cytoplasmic dynein mutation shows motor behavior deficits consistent with Charcot-Marie-Tooth type 2O disease.

    PubMed

    Sabblah, Thywill T; Nandini, Swaran; Ledray, Aaron P; Pasos, Julio; Calderon, Jami L Conley; Love, Rachal; King, Linda E; King, Stephen J

    2018-01-29

    Charcot-Marie-Tooth disease (CMT) is a peripheral neuromuscular disorder in which axonal degeneration causes progressive loss of motor and sensory nerve function. The loss of motor nerve function leads to distal muscle weakness and atrophy, resulting in gait problems and difficulties with walking, running, and balance. A mutation in the cytoplasmic dynein heavy chain (DHC) gene was discovered to cause an autosomal dominant form of the disease designated Charcot-Marie-Tooth type 2 O disease (CMT2O) in 2011. The mutation is a single amino acid change of histidine into arginine at amino acid 306 (H306R) in DHC. In order to understand the onset and progression of CMT2, we generated a knock-in mouse carrying the corresponding CMT2O mutation (H304R/+). We examined H304R/+ mouse cohorts in a 12-month longitudinal study of grip strength, tail suspension, and rotarod assays. H304R/+ mice displayed distal muscle weakness and loss of motor coordination phenotypes consistent with those of individuals with CMT2. Analysis of the gastrocnemius of H304R/+ male mice showed prominent defects in neuromuscular junction (NMJ) morphology including reduced size, branching, and complexity. Based on these results, the H304R/+ mouse will be an important model for uncovering functions of dynein in complex organisms, especially related to CMT onset and progression.

  5. Arm blood flow and metabolism during arm and combined arm and leg exercise in humans

    PubMed Central

    Volianitis, S; Secher, N H

    2002-01-01

    The cardiovascular response to exercise with several groups of skeletal muscle suggests that work with the arms may decrease leg blood flow. This study evaluated whether intense exercise with the legs would have a similar effect on arm blood flow (Q̇arm) and O2 consumption (V̇O2,arm). Ten healthy male subjects (age 21 ± 1 year; mean ± S.D.) performed arm cranking at 80 % of maximum arm work capacity (A trial) and combined arm cranking with cycling at 60 % of maximum leg work capacity (A + L trial). The combined trial was a maximum effort for 5-6 min. Q̇arm measurement by thermodilution in the axilliary vein and arterial and venous blood samples permitted calculation of V̇O2,arm. During the combined trial, Q̇arm was reduced by 0.58 ± 0.25 l min−1 (19.1 ± 3.0 %, P < 0.05) from the value during arm cranking (3.00 ± 0.46 l min−1). The arterio-venous O2 difference increased from 122 ± 15 ml l−1 during the arm trial to 150 ± 21 ml l−1 (P < 0.05) during the combined trial. Thus, V̇O2,arm (0.45 ± 0.06 l min−1) was reduced by 9.6 ± 6.3 % (P < 0.05) and arm vascular conductance from 27 ± 4 to 23 ± 3 ml min−1 (mmHg)−1 (P < 0.05) as noradrenaline spillover from the arm increased from 7.5 ± 3.5 to 13.8 ± 4.2 nmol min−1 (P < 0.05). The data suggest that during maximal whole body exercise in humans, arm vasoconstriction is established to an extent that affects oxygen delivery to and utilisation by working skeletal muscles. PMID:12411540

  6. Armed conflict and child health

    PubMed Central

    Rieder, Michael; Choonara, Imti

    2012-01-01

    Summary Armed conflict has a major impact on child health throughout the world. One in six children worldwide lives in an area of armed conflict and civilians are more likely to die than soldiers as a result of the conflict. In stark contrast to the effect on children, the international arms trade results in huge profits for the large corporations involved in producing arms, weapons and munitions. Armed conflict is not inevitable but is an important health issue that should be prevented. PMID:21393303

  7. Neural processes mediating the preparation and release of focal motor output are suppressed or absent during imagined movement

    PubMed Central

    Eagles, Jeremy S.; Carlsen, Anthony N.

    2016-01-01

    Movements that are executed or imagined activate a similar subset of cortical regions, but the extent to which this activity represents functionally equivalent neural processes is unclear. During preparation for an executed movement, presentation of a startling acoustic stimulus (SAS) evokes a premature release of the planned movement with the spatial and temporal features of the tasks essentially intact. If imagined movement incorporates the same preparatory processes as executed movement, then a SAS should release the planned movement during preparation. This hypothesis was tested using an instructed-delay cueing paradigm during which subjects were required to rapidly release a handheld weight while maintaining the posture of the arm or to perform first-person imagery of the same task while holding the weight. In a subset of trials, a SAS was presented at 1500, 500, or 200 ms prior to the release cue. Task-appropriate preparation during executed and imagined movements was confirmed by electroencephalographic recording of a contingent negative variation waveform. During preparation for executed movement, a SAS often resulted in premature release of the weight with the probability of release progressively increasing from 24 % at −1500 ms to 80 % at −200 ms. In contrast, the SAS rarely (<2 % of trials) triggered a release of the weight during imagined movement. However, the SAS frequently evoked the planned postural response (suppression of bicep brachii muscle activity) irrespective of the task or timing of stimulation (even during periods of postural hold without preparation). These findings provide evidence that neural processes mediating the preparation and release of the focal motor task (release of the weight) are markedly attenuated or absent during imagined movement and that postural and focal components of the task are prepared independently. PMID:25744055

  8. The differential influence of absent and harsh fathers on juvenile delinquency.

    PubMed

    Simmons, Cortney; Steinberg, Laurence; Frick, Paul J; Cauffman, Elizabeth

    2018-01-01

    Researchers have identified father absence as a contributor to juvenile delinquency. Consequently, politicians and community leaders are making efforts to re-engage fathers. However, it is possible that the presence of fathers is not, in itself, a substantial protective factor and, in some cases, can even be more detrimental than father absence. Employing a diverse sample of male juvenile offenders in the U.S. (ages 13-17), the present study examined the differential effects of absent fathers and harsh fathers on delinquency. Results indicated that youth in the harsh-father group engaged in more offending behaviors and used more substances than youth in the absent-father group. This difference remained even after controlling for the mother-child relationship. Implications of these findings for future research and delinquency prevention programs are discussed. Copyright © 2017 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  9. Exploring What’s Missing: What Do Target Absent Trials Reveal About Autism Search Superiority?

    PubMed Central

    Keehn, Brandon; Joseph, Robert M.

    2016-01-01

    We used eye-tracking to investigate the roles of enhanced discrimination and peripheral selection in superior visual search in autism spectrum disorder (ASD). Children with ASD were faster at visual search than their typically developing peers. However, group differences in performance and eye-movements did not vary with the level of difficulty of discrimination or selection. Rather, consistent with prior ASD research, group differences were mainly the effect of faster performance on target-absent trials. Eye-tracking revealed a lack of left-visual-field search asymmetry in ASD, which may confer an additional advantage when the target is absent. Lastly, ASD symptomatology was positively associated with search superiority, the mechanisms of which may shed light on the atypical brain organization that underlies social-communicative impairment in ASD. PMID:26762114

  10. The social-cognitive basis of infants' reference to absent entities.

    PubMed

    Bohn, Manuel; Zimmermann, Luise; Call, Josep; Tomasello, Michael

    2018-04-06

    Recent evidence suggests that infants as young as 12 month of age use pointing to communicate about absent entities. The tacit assumption underlying these studies is that infants do so based on tracking what their interlocutor experienced in a previous shared interaction. The present study addresses this assumption empirically. In three experiments, 12-month-old infants could request additional desired objects by pointing to the location in which these objects were previously located. We systematically varied whether the adult from whom infants were requesting had previously experienced the former content of the location with the infant. Infants systematically adjusted their pointing to the now empty location to what they experienced with the adult previously. These results suggest that infants' ability to communicate about absent referents is based on an incipient form of common ground. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Mayer Rokitansky Kuster Hauser (MRKH) syndrome with absent thumbs and big toes.

    PubMed

    Yunus, Mahira

    2014-01-01

    Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a rare developmental failure of Müllerian ducts. Principle clinical features of MRKH syndrome are primary amenorrhoea associated with congenital absence of vagina, uterine anomalies, normal ovaries, 46 XX karyotype with normal female secondary sexual characteristics and frequent association with renal, skeletal, and other congenital anomalies. A case of a 3-year-old child with congenitally absent thumbs and big toes is reported herein; she was brought in with complaints of urinary incontinence. Radiological investigation (ultrasound and magnetic resonance imaging (MRI) scan) revealed absent uterus and vagina while both ovaries were normal. Intravenous urography (IVU) study showed bifid pelvicalyceal systems bilaterally. Karyotyping revealed a 46 XX female phenotype. Laparoscopy confirmed normal ovaries bilaterally and small unfused uterine buds lying beside both ovaries on each side of pelvis. Early diagnosis of MRKH syndrome is essential for timely planning of vaginal and (if possible) uterine reconstructive surgeries.

  12. The target of daptomycin is absent from Escherichia coli and other gram-negative pathogens.

    PubMed

    Randall, Christopher P; Mariner, Katherine R; Chopra, Ian; O'Neill, Alex J

    2013-01-01

    Antistaphylococcal agents commonly lack activity against Gram-negative bacteria like Escherichia coli owing to the permeability barrier presented by the outer membrane and/or the action of efflux transporters. When these intrinsic resistance mechanisms are artificially compromised, such agents almost invariably demonstrate antibacterial activity against Gram negatives. Here we show that this is not the case for the antibiotic daptomycin, whose target appears to be absent from E. coli and other Gram-negative pathogens.

  13. A review of supernumerary and absent limbs and digits of the upper limb.

    PubMed

    Klaassen, Zachary; Choi, Monica; Musselman, Ruth; Eapen, Deborah; Tubbs, R Shane; Loukas, Marios

    2012-03-01

    For years people have been enamored by anomalies of the human limbs, particularly supernumerary and absent limbs and digits. Historically, there are a number of examples of such anomalies, including royal families of ancient Chaldea, tribes from Arabia, and examples from across nineteenth century Europe. The development of the upper limbs in a growing embryo is still being elucidated with the recent advent of homeobox genes, but researchers agree that upper limbs develop between stages 12-23 through a complex embryological process. Maternal thalidomide intake during limb development is known to cause limb reduction and subsequent amelia or phocomelia. Additionally, a number of clinical reports have illustrated different limb anomaly cases, with each situation unique in phenotype and developmental abnormality. Supernumerary and absent limbs and digits are not unique to humans, and a number of animal cases have also been reported. This review of the literature illustrates the historical, anatomical, and clinical aspects of supernumerary and absent limbs and digits for the upper limb.

  14. Case report: absent C6 cervical pedicle in a collegiate football player.

    PubMed

    Fowler, John R; Moyer, Ray A

    2010-06-01

    Congenital absence of a cervical pedicle is a rare clinical finding with only 70 reported cases in the literature from 1946 until present. The congenitally absent pedicle has clinical importance owing to the frequency of misdiagnosis and inappropriate invasive treatments. We present the case of a 21-year-old college football player who experienced neck and shoulder pain after violent twisting of his neck by the face mask. The player walked off the field under his own power. He was sent to the locker room, where he underwent right shoulder and cervical spine radiographs. Initial review of the radiographs raised concern for a jumped right C6 facet. The patient then underwent CT and MRI of the cervical spine, confirming the diagnosis of an absent cervical pedicle. He was treated nonoperatively for a short time and completed the season. He had no symptoms at last followup at 8 months. The most frequent location of the absent cervical pedicle is at the C6 level, and the next most common is at the C5 level. Neural compression or instability is uncommon and nonsurgical treatment is the mainstay of treatment. Misdiagnosis can lead to inappropriate treatment such as halo or tong application with traction, which occurred in seven of 57 cases in one series, and exploratory surgery, which occurred in four of 57 cases.

  15. Cardiac-locked bursts of muscle sympathetic nerve activity are absent in familial dysautonomia

    PubMed Central

    Macefield, Vaughan G; Norcliffe-Kaufmann, Lucy; Axelrod, Felicia B; Kaufmann, Horacio

    2013-01-01

    Familial dysautonomia (Riley–Day syndrome) is an hereditary sensory and autonomic neuropathy (HSAN type III), expressed at birth, that is associated with reduced pain and temperature sensibilities and absent baroreflexes, causing orthostatic hypotension as well as labile blood pressure that increases markedly during emotional excitement. Given the apparent absence of functional baroreceptor afferents, we tested the hypothesis that the normal cardiac-locked bursts of muscle sympathetic nerve activity (MSNA) are absent in patients with familial dysautonomia. Tungsten microelectrodes were inserted percutaneously into muscle or cutaneous fascicles of the common peroneal nerve in 12 patients with familial dysautonomia. Spontaneous bursts of MSNA were absent in all patients, but in five patients we found evidence of tonically firing sympathetic neurones, with no cardiac rhythmicity, that increased their spontaneous discharge during emotional arousal but not during a manoeuvre that unloads the baroreceptors. Conversely, skin sympathetic nerve activity (SSNA), recorded in four patients, appeared normal. We conclude that the loss of phasic bursts of MSNA and the loss of baroreflex modulation of muscle vasoconstrictor drive contributes to the poor control of blood pressure in familial dysautonomia, and that the increase in tonic firing of muscle vasoconstrictor neurones contributes to the increase in blood pressure during emotional excitement. PMID:23165765

  16. Controller arm for a remotely related slave arm

    NASA Technical Reports Server (NTRS)

    Salisbury, J. K., Jr. (Inventor)

    1979-01-01

    A segmented controller arm configured and dimensioned to form a miniature kinematic replica of a remotely related slave arm is disclosed. The arm includes: (1) a plurality of joints for affording segments of the arm simultaneous angular displacement about a plurality of pairs of intersecting axes, (2) a plurality of position sensing devices for providing electrical signals indicative of angular displacement imparted to corresponding segments of the controller shaft about the axes, and (3) a control signal circuit for generating control signals to be transmitted to the slave arm. The arm is characterized by a plurality of yokes, each being supported for angular displacement about a pair of orthogonally related axes and counterbalanced against gravitation by a cantilevered mass.

  17. ARM Spacecraft Illustration

    NASA Image and Video Library

    2016-09-20

    This graphic depicts the Asteroid Redirect Vehicle conducting a flyby of its target asteroid. During these flybys, the Asteroid Redirect Mission (ARM) would come within 0.6 miles (1 kilometer), generating imagery with resolution of up to 0.4 of an inch (1 centimeter) per pixel. The robotic segment of ARM will demonstrate advanced, high-power, high-throughput solar electric propulsion; advanced autonomous precision proximity operations at a low-gravity planetary body; and controlled touchdown and liftoff with a multi-ton mass. The crew segment of the mission will include spacewalk activities for sample selection, extraction, containment and return; and mission operations of integrated robotic and crewed vehicle stack -- all key components of future in-space operations for human missions to the Mars system. After collecting a multi-ton boulder from the asteroid, the robotic spacecraft will redirect the boulder to a crew-accessible orbit around the moon, where NASA plans to conduct a series of proving ground missions in the 2020s that will help validate capabilities needed for NASA's Journey to Mars. http://photojournal.jpl.nasa.gov/catalog/PIA21062

  18. The absent bow tie sign in bucket-handle tears of the menisci in the knee.

    PubMed

    Helms, C A; Laorr, A; Cannon, W D

    1998-01-01

    Bucket-handle tears of the menisci are one of the most frequently missed diagnoses in MR examinations of the knee. This article describes the "absent bow tie sign," which can be used to identify bucket-handle tears on routine MR examinations of the knee. The arthroscopic surgical reports (n = 350) from a single orthopedic surgeon's practice during a 24-month period were examined for patients who had a diagnosis of bucket-handle tear and who underwent MR imaging before surgery (n = 32). The MR examinations were retrospectively evaluated for the presence of a bow tie sign. The bow tie sign was considered normal when two sagittal images showed the body segment (a bow tie appearance). The bow tie sign was considered abnormal, consistent with a bucket-handle tear, when only one or no body segment was seen (the absent bow tie sign). Coronal images were evaluated for a truncated meniscus. Also, each MR examination was scrutinized for a displaced fragment and a double posterior cruciate ligament (PCL) sign. Thirty-three bucket-handle tears were found at arthroscopy in 32 patients. One patient had tears of the medial and lateral menisci. The absent bow tie sign was seen in 32 of the 33 cases (sensitivity, 97%) and correlated with the medial or lateral meniscus that was reported torn at arthroscopy. The single false-negative result occurred in a patient with a nondisplaced bucket-handle tear. The findings in 31 contralateral normal menisci were all negative for an absent bow tie sign (specificity, 100%). A displaced fragment was found in 30 (94%) of 32 cases. The coronal images showed a truncated meniscus in 21 (64%) of 33 cases. A double PCL sign was seen in 10 (30%) of 33 cases. The absent bow tie sign is an easily applied finding that can be used with good sensitivity to diagnose bucket-handle tears of the menisci on MR imaging. This sign has a higher accuracy rate than other findings common with bucket-handle tears, such as displaced fragments, a truncated appearance of

  19. Human Immunodeficiency Virus Type 1 Employs the Cellular Dynein Light Chain 1 Protein for Reverse Transcription through Interaction with Its Integrase Protein

    PubMed Central

    Jayappa, Kallesh Danappa; Ao, Zhujun; Wang, Xiaoxia; Mouland, Andrew J.; Shekhar, Sudhanshu; Yang, Xi

    2015-01-01

    ABSTRACT In this study, we examined the requirement for host dynein adapter proteins such as dynein light chain 1 (DYNLL1), dynein light chain Tctex-type 1 (DYNLT1), and p150Glued in early steps of human immunodeficiency virus type 1 (HIV-1) replication. We found that the knockdown (KD) of DYNLL1, but not DYNLT1 or p150Glued, resulted in significantly lower levels of HIV-1 reverse transcription in cells. Following an attempt to determine how DYNLL1 could impact HIV-1 reverse transcription, we detected the DYNLL1 interaction with HIV-1 integrase (IN) but not with capsid (CA), matrix (MA), or reverse transcriptase (RT) protein. Furthermore, by mutational analysis of putative DYNLL1 interaction motifs in IN, we identified the motifs 52GQVD and 250VIQD in IN as essential for DYNLL1 interaction. The DYNLL1 interaction-defective IN mutant HIV-1 (HIV-1INQ53A/Q252A) exhibited impaired reverse transcription. Through further investigations, we have also detected relatively smaller amounts of particulate CA in DYNLL1-KD cells or in infections with HIV-1INQ53A/Q252A mutant virus. Overall, our study demonstrates the novel interaction between HIV-1 IN and cellular DYNLL1 proteins and suggests the requirement of this virus-cell interaction for proper uncoating and efficient reverse transcription of HIV-1. IMPORTANCE Host cellular DYNLL1, DYNLT1, and p150Glued proteins have been implicated in the replication of several viruses. However, their roles in HIV-1 replication have not been investigated. For the first time, we demonstrated that during viral infection, HIV-1 IN interacts with DYNLL1, and their interaction was found to have a role in proper uncoating and efficient reverse transcription of HIV-1. Thus, interaction of IN and DYNLL1 may be a potential target for future anti-HIV therapy. Moreover, while our study has evaluated the involvement of IN in HIV-1 uncoating and reverse transcription, it also predicts a possible mechanism by which IN contributes to these early viral

  20. ML Crew Access Arm Move

    NASA Image and Video Library

    2017-10-16

    The Orion crew access arm departs Precision Fabricating and Cleaning in Cocoa, Florida, atop a flatbed truck. The access arm is transported to a storage location at NASA's Kennedy Space Center in Florida. Later this month, the arm will be transported to the mobile launcher (ML) tower at the center. The crew access arm will be located at about the 274-foot level on the tower. It will rotate from its retracted position and interface with the Orion crew hatch location to provide entry to the Orion crew module. The Ground Systems Development and Operations Program is overseeing installation of umbilicals and launch accessories on the ML tower.

  1. Recovery in the Severely Impaired Arm Post-stroke after Mirror Therapy - a Randomized Controlled Study.

    PubMed

    Chan, Wing Chiu; Au-Yeung, Stephanie Suk Yin

    2018-03-09

    This study aimed to examine the effectiveness of mirror therapy (MT) on recovery in the severely impaired arm after stroke. Using single-blind randomized controlled design, patients with severely impaired arm within 1-month post-stroke were assigned to received MT (n=20) or control therapy (CT) (n=21), 30min. twice daily for 4 weeks in addition to conventional rehabilitation. During MT and CT, subjects practiced similar structured exercises in both arms, except that mirror reflection of the unaffected arm was the visual feedback for MT, but mirror was absent for CT so that subjects could watch both arms in exercise. Fugl-Meyer Assessment (FMA) and Wolf Motor Function Test (WMFT) were the outcome measurements. After the intervention, both MT and CT groups had significant arm recovery similarly in FMA (p=0.867), WMFT-Time (p=0.947) and WMFT-Functional Ability Scale (p=0.676). MT or CT which involved exercises concurrently for the paretic and unaffected arms during subacute stroke promoted similar motor recovery in the severely impaired arm.

  2. The Neanderthal lower arm.

    PubMed

    De Groote, Isabelle

    2011-10-01

    Neanderthal forearms have been described as being very powerful. Different individual features in the lower arm bones have been described to distinguish Neanderthals from modern humans. In this study, the overall morphology of the radius and ulna is considered, and morphological differences among Neanderthals, Upper Paleolithic Homo sapiens and recent H. sapiens are described. Comparisons among populations were made using a combination of 3D geometric morphometrics and standard multivariate methods. Comparative material included all available complete radii and ulnae from Neanderthals, early H. sapiens and archaeological and recent human populations, representing a wide geographical and lifestyle range. There are few differences among the populations when features are considered individually. Neanderthals and early H. sapiens fell within the range of modern human variation. When the suite of measurements and shapes were analyzed, differences and similarities became apparent. The Neanderthal radius is more laterally curved, has a more medially placed radial tuberosity, a longer radial neck, a more antero-posteriorly ovoid head and a well-developed proximal interosseous crest. The Neanderthal ulna has a more anterior facing trochlear notch, a lower M. brachialis insertion, larger relative mid-shaft size and a more medio-lateral and antero-posterior sinusoidal shaft. The Neanderthal lower arm morphology reflects a strong cold-adapted short forearm. The forearms of H. sapiens are less powerful in pronation and supination. Many differences between Neanderthals and H. sapiens can be explained as a secondary consequence of the hyper-polar body proportions of the Neanderthals, but also as retentions of the primitive condition of other hominoids. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Mands for Information Using "How" Under EO-Absent and EO-Present Conditions.

    PubMed

    Shillingsburg, M Alice; Bowen, Crystal N; Valentino, Amber L

    2014-06-01

    The present study replicates and extends previous research on teaching "How?" mands for information to children with autism. The experimental preparation involved mand training in the context of completing preferred activities and included training and testing under conditions when the establishing operation (EO) was present and absent. Results show that two children with autism acquired mands for information using How? only in situations where information was valuable (i.e., the EO was present); they then consistently made use of the information provided in activity completion. Generalization to novel, untaught situations was assessed.

  4. Creating insight when the literature is absent: the circle of advisors.

    PubMed

    Batcheller, Joyce; Yoder-Wise, Patricia S

    2011-01-01

    When changes happen as rapidly as they do today, the literature is often absent. Although related literature may be available to substantiate a direction to take when faced with some issue to resolve, that literature may be vague in terms of its applicability within health care. The idea of a circle of advisors was instituted to gain insight from experts who had faced similar challenges and often had extensive networks of shared experiences. The use of a sequential dialog identified specific talents to be developed in a chief nurse executive enculturation program.

  5. Profuse congenital familial milia with absent dermatoglyphics (Basan's Syndrome): description of a new family.

    PubMed

    Luna, Paula Carolina; Larralde, Margarita

    2012-01-01

    Milia are common, small, keratin-containing cysts frequently seen in all age groups. They may arise spontaneously or develop after a variety of stimuli. They can be found alone or as part of syndromes. We present a female neonate born not only with profuse facial milia, but also with acral bullae and absent dermatoglyphics. Similar features were seen in several members of her family. These findings correspond to the syndrome known as Basan's syndrome, a rare autosomal-dominant inherited dermatosis characterized by profuse congenital milia, transient neonatal acral bullae, and absence of dermatoglyphics. © 2011 Wiley Periodicals, Inc.

  6. Deletion of the Dynein Heavy-Chain Gene DYN1 Leads to Aberrant Nuclear Positioning and Defective Hyphal Development in Candida albicans

    PubMed Central

    Martin, R.; Walther, A.; Wendland, J.

    2004-01-01

    Cytoplasmic dynein is a microtubule-associated minus-end-directed motor protein. CaDYN1 encodes the single dynein heavy-chain gene of Candida albicans. The open reading frames of both alleles of CaDYN1 were completely deleted via a PCR-based approach. Cadyn1 mutants are viable but grow more slowly than the wild type. In vivo time-lapse microscopy was used to compare growth of wild-type (SC5314) and dyn1 mutant strains during yeast growth and after hyphal induction. During yeast-like growth, Cadyn1 strains formed chains of cells. Chromosomal TUB1-GFP and HHF1-GFP alleles were used both in wild-type and mutant strains to monitor the orientation of mitotic spindles and nuclear positioning in C. albicans. In vivo fluorescence time-lapse analyses with HHF1-GFP over several generations indicated defects in dyn1 cells in the realignment of spindles with the mother-daughter axis of yeast cells compared to that of the wild type. Mitosis in the dyn1 mutant, in contrast to that of wild-type yeast cells, was very frequently completed in the mother cells. Nevertheless, daughter nuclei were faithfully transported into the daughter cells, resulting in only a small number of multinucleate cells. Cadyn1 mutant strains responded to hypha-inducing media containing l-proline or serum with initial germ tube formation. Elongation of the hyphal tubes eventually came to a halt, and these tubes showed a defect in the tipward localization of nuclei. Using a heterozygous DYN1/dyn1 strain in which the remaining copy was controlled by the regulatable MAL2 promoter, we could switch between wild-type and mutant phenotypes depending on the carbon source, indicating that the observed mutant phenotypes were solely due to deletion of DYN1. PMID:15590831

  7. LISA Long-Arm Interferometry

    NASA Technical Reports Server (NTRS)

    Thorpe, James I.

    2009-01-01

    An overview of LISA Long-Arm Interferometry is presented. The contents include: 1) LISA Interferometry; 2) Constellation Design; 3) Telescope Design; 4) Constellation Acquisition; 5) Mechanisms; 6) Optical Bench Design; 7) Phase Measurement Subsystem; 8) Phasemeter Demonstration; 9) Time Delay Interferometry; 10) TDI Limitations; 11) Active Frequency Stabilization; 12) Spacecraft Level Stabilization; 13) Arm-Locking; and 14) Embarassment of Riches.

  8. Layers of Experience Using "Arms"

    ERIC Educational Resources Information Center

    Brown, Laurinda; Coles, Alf; Ball, Derek; Morton, Pat; Coles, Matt; Ordman, Louise; Orr, Barry; Lam, Tung Ken

    2008-01-01

    This article presents the authors' personal accounts and their experiences in working on mathematics using "arms." "Arms" is an idea that first appeared as a program written by John Warwick and David Wooldridge in an ATM publication "Some Lessons in Mathematics with a Microcomputer," 1983. The introduction to…

  9. An MR-compatible gyroscope-based arm movement tracking system.

    PubMed

    Shirinbayan, S Iman; Rieger, Jochem W

    2017-03-15

    Functional magnetic resonance imaging is well suited to link neural population activation with movement parameters of complex natural arm movements. However, currently existing MR-compatible arm tracking devices are not constructed to measure arm joint movement parameters of unrestricted movements. Therefore, to date most research focuses on simple arm movements or includes very little knowledge about the actual movement kinematics. We developed a low cost gyroscope-based arm movement tracking system (GAMTS) that features MR-compatibility. The system consists of dual-axis analogue gyroscopes that measure rotations of upper and lower arm joints. After MR artifact reduction, the rotation angles of the individual arm joints are calculated and used to animate a realistic arm model that is implemented in the OpenSim platform. The OpenSim platform can then provide the kinematics of any point on the arm model. In order to demonstrate the capabilities of the system, we first assessed the quality of reconstructed wrist movements in a low-noise environment where typical MR-related problems are absent and finally, we validated the reconstruction in the MR environment. The system provides the kinematics of the whole arm when natural unrestricted arm movements are performed inside the MR-scanner. The GAMTS is reliably capable of reconstructing the kinematics of trajectories and the reconstruction error is small in comparison with the movement induced variation of speed, displacement, and rotation. Moreover, the system can be used to probe brain areas for their correlation with movement kinematics. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. The role of within-compound associations in learning about absent cues.

    PubMed

    Witnauer, James E; Miller, Ralph R

    2011-05-01

    When two cues are reinforced together (in compound), most associative models assume that animals learn an associative network that includes direct cue-outcome associations and a within-compound association. All models of associative learning subscribe to the importance of cue-outcome associations, but most models assume that within-compound associations are irrelevant to each cue's subsequent behavioral control. In the present article, we present an extension of Van Hamme and Wasserman's (Learning and Motivation 25:127-151, 1994) model of retrospective revaluation based on learning about absent cues that are retrieved through within-compound associations. The model was compared with a model lacking retrieval through within-compound associations. Simulations showed that within-compound associations are necessary for the model to explain higher-order retrospective revaluation and the observed greater retrospective revaluation after partial reinforcement than after continuous reinforcement alone. These simulations suggest that the associability of an absent stimulus is determined by the extent to which the stimulus is activated through the within-compound association.

  11. The role of within-compound associations in learning about absent cues

    PubMed Central

    Witnauer, James E.

    2011-01-01

    When two cues are reinforced together (in compound), most associative models assume that animals learn an associative network that includes direct cue–outcome associations and a within-compound association. All models of associative learning subscribe to the importance of cue–outcome associations, but most models assume that within-compound associations are irrelevant to each cue's subsequent behavioral control. In the present article, we present an extension of Van Hamme and Wasserman's (Learning and Motivation 25:127–151, 1994) model of retrospective revaluation based on learning about absent cues that are retrieved through within-compound associations. The model was compared with a model lacking retrieval through within-compound associations. Simulations showed that within-compound associations are necessary for the model to explain higher-order retrospective revaluation and the observed greater retrospective revaluation after partial reinforcement than after continuous reinforcement alone. These simulations suggest that the associability of an absent stimulus is determined by the extent to which the stimulus is activated through the within-compound association. PMID:21264569

  12. Histone H3 is absent from organelle nucleoids in BY-2 cultured tobacco cells.

    PubMed

    Takusagawa, Mari; Tamotsu, Satoshi; Sakai, Atsushi

    2013-07-01

    The core histone proteins (H2A, H2B, H3 and H4) are nuclear-localised proteins that play a central role in the formation of nucleosome structure. They have long been considered to be absent from extra-nuclear, DNA-containing organelles; that is plastids and mitochondria. Recently, however, the targeting of core histone H3 to mitochondria, and the presence of nucleosome-like structures in mitochondrial nucleoids, were proposed in cauliflower and tobacco respectively. Thus, we examined whether histone H3 was present in plant organelles and participated in the organisation of nucleoid structure, using highly purified organelles and organelle nucleoids isolated from BY-2 cultured tobacco cells. Immunofluorescence microscopic observations and Western blotting analyses demonstrated that histone H3 was absent from organelles and organelle nucleoids, consistent with the historical hypothesis. Thus, the organisation of organelle nucleoids, including putative nucleosome-like repetitive structures, should be constructed and maintained without participation of histone H3. © 2013 International Federation for Cell Biology.

  13. Tetralogy of Fallot with absent pulmonary valve syndrome; appropriate surgical strategies.

    PubMed

    Shahid, Fatima; Siddiqui, Maria Tariq; Amanullah, Muhammad Muneer

    2015-05-01

    To evaluate patients presenting with Tetralogy of Fallot with absent pulmonary valve syndrome to a tertiary care hospital and their surgical management. The retrospective study was conducted at Congenital Cardiac Services, Aga Khan University Hospital, Karachi, Pakistan, and comprised data of Tetralogy of Fallot patients between April 2007 and June 2012. Data was analysed together with follow-up echocardiography. Variables assessed included demographics, imaging, operative technique, complications, post-operative recovery and follow-up echocardiography. SPSS 17 was used for statistical analysis. Of the 204 patients, 6 (3%) had undergone surgical correction for Tetralogy of Fallot with absent pulmonary valve syndrome. All 6(100%) patients underwent complete repair. Median age for surgery was 8.5 years (range: 0.5-29 years). Of the different surgical strategies used, Contegra and Bioprosthetic valve placement had satisfactory outcome with minimal gradient at Right Ventricular Outflow Tract, good ventricular function and mild valvular regurgitation. One (16.6%) patient with Trans Annular Patch developed post-operative Right Ventricle Outflow Tract gradient of 80mmHg with moderate pulmonary regurgitation. One (16.6%) patient with monocusp valve developed free pulmonary regurgitation at 6 months. The other 4(66.6%) patients are currently free from any complications or re-intervention. Early surgery is preferred in symptomatic patients. The repair depends upon achieving integrity of pulmonary circulation which is best achieved by using right ventricle to pulmonary artery conduit or inserting a pulmonary valve.

  14. How do octopuses use their arms?

    PubMed

    Mather, J A

    1998-09-01

    A taxonomy of the movement patterns of the 8 flexible arms of octopuses is constructed. Components consist of movements of the arm itself, the ventral suckers and their stalks, as well as the relative position of arms and the skin web between them. Within 1 arm, combinations of components result in a variety of behaviors. At the level of all arms, 1 group of behaviors is described as postures, on the basis of the spread of all arms and the web to make a 2-dimensional surface whose position differs in the 3rd dimension. Another group of arm behaviors is actions, more or less coordinated and involving several to all arms. Arm control appears to be based on radial symmetry, relative equipotentiality of all arms, relative independence of each arm, and separability of components within the arm. The types and coordination of arm behaviors are discussed with relationship to biomechanical limits, muscle structures, and neuronal programming.

  15. Orthotic arm joint. [for use in mechanical arms

    NASA Technical Reports Server (NTRS)

    Dane, D. H. (Inventor)

    1974-01-01

    An improved orthopedic (orthotic) arm joint that can be used in various joint of mechanical arms is described. The arm joints includes a worm, which is coupled to an electric motor for rotating a worm gear carried within a rotatable housing. The worm gear is supported on a thrust bearing and the rotatable housing is supported on a radial thrust bearing. A bolt extends through the housing, bearings, and worm gear for securing the device together. A potentiometer extends through the bolt, and is coupled to the rotatable housing for rotating therewith, so as to produce an electrical signal indicating the angular position of the rotatable housing.

  16. ML Crew Access Arm Move

    NASA Image and Video Library

    2017-11-09

    The Orion crew access arm is secured in a storage location at NASA's Kennedy Space Center in Florida. The access arm will be prepared for its move to the mobile launcher (ML) tower near the Vehicle Assembly Building at the center. The crew access arm will be installed at about the 274-foot level on the tower. It will rotate from its retracted position and interface with the Orion crew hatch location to provide entry to the Orion crew module. The Ground Systems Development and Operations Program is overseeing installation of umbilicals and launch accessories on the ML tower.

  17. ML Crew Access Arm Move

    NASA Image and Video Library

    2017-11-10

    A heavy-load transport truck carries the Orion crew access arm along the NASA Causeway east toward State Road 3 at NASA's Kennedy Space Center in Florida. The access arm will be moved to the mobile launcher (ML) near the Vehicle Assembly Building at the center. The crew access arm will be installed at about the 274-foot level on the mobile launcher tower. It will rotate from its retracted position and interface with the Orion crew hatch location to provide entry to the Orion crew module. The Ground Systems Development and Operations Program is overseeing installation of umbilicals and launch accessories on the ML tower to prepare for Exploration Mission-1.

  18. ML Crew Access Arm Move

    NASA Image and Video Library

    2017-11-10

    A heavy-load transport truck carries the Orion crew access arm along the NASA Causeway east toward State Road 3 at NASA's Kennedy Space Center in Florida. The access arm will be moved to the mobile launcher (ML) near the Vehicle Assembly Building at the center. The crew access arm will be installed at about the 274-foot level on the tower. It will rotate from its retracted position and interface with the Orion crew hatch location to provide entry to the Orion crew module. The Ground Systems Development and Operations Program is overseeing installation of umbilicals and launch accessories on the ML tower to prepare for Exploration Mission-1.

  19. Irregular or absent periods--what can an ultrasound scan tell you?

    PubMed

    Khalid, Asma

    2004-02-01

    Transvaginal ultrasonography has increased our appreciation of the physiological changes in the ovary and endometrium that occur during the normal menstrual cycle. It has become a primary investigative tool in women with irregular or absent periods. Its usefulness in cases of primary amenorrhoea to assess anatomy is also undisputed although it may have limitations in terms of its specificity. However, the interpretation of ultrasound images in women with irregular menses or secondary amenorrhoea is not entirely straightforward. This is particularly true in the diagnosis of polycystic ovary syndrome, a condition of uncertain aetiology, which may present with oligoamenorrhoea. This chapter aims to discuss the benefits and limitations of ultrasound while taking into account the broad overlap between normal and abnormal physiology, some of which has still to be elucidated.

  20. The role of past interactions in great apes' communication about absent entities.

    PubMed

    Bohn, Manuel; Call, Josep; Tomasello, Michael

    2016-11-01

    Recent evidence suggests that great apes can use the former location of an entity to communicate about it. In this study we built on these findings to investigate the social-cognitive foundations of great apes' communicative abilities. We tested whether great apes (n = 35) would adjust their requests for absent entities to previous interactions they had with their interlocutor. We manipulated the apes' experience with respect to the interlocutor's knowledge about the previous content of the now-empty location as well as their experience with the interlocutor's competence to provide additional food items. We found that apes adjusted their requests to both of these aspects but failed to integrate them with one another. These results demonstrate a surprising amount of flexibility in great apes' communicative abilities while at the same time suggesting some important limitations in their social communicative skills. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  1. When Absence of Evidence Is Evidence of Absence: Rational Inferences From Absent Data.

    PubMed

    Hsu, Anne S; Horng, Andy; Griffiths, Thomas L; Chater, Nick

    2017-05-01

    Identifying patterns in the world requires noticing not only unusual occurrences, but also unusual absences. We examined how people learn from absences, manipulating the extent to which an absence is expected. People can make two types of inferences from the absence of an event: either the event is possible but has not yet occurred, or the event never occurs. A rational analysis using Bayesian inference predicts that inferences from absent data should depend on how much the absence is expected to occur, with less probable absences being more salient. We tested this prediction in two experiments in which we elicited people's judgments about patterns in the data as a function of absence salience. We found that people were able to decide that absences either were mere coincidences or were indicative of a significant pattern in the data in a manner that was consistent with predictions of a simple Bayesian model. Copyright © 2016 Cognitive Science Society, Inc.

  2. Importance of Absent Neoplastic Epithelium in Patients Treated With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

    PubMed

    Enblad, Malin; Birgisson, Helgi; Wanders, Alkwin; Sköldberg, Filip; Ghanipour, Lana; Graf, Wilhelm

    2016-04-01

    The importance of absent neoplastic epithelium in specimens from cytoreductive surgery (CRS) is unknown. This study aimed to investigate the prevalence and prognostic value of histopathology without neoplastic epithelium in patients treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). Data were extracted from medical records and histopathology reports for patients treated with initial CRS and HIPEC at Uppsala University Hospital, Sweden, between 2004 and 2012. Patients with inoperable disease and patients undergoing palliative non-CRS surgery were excluded from the study. Patients lacking neoplastic epithelium in surgical specimens from CRS, with or without mucin, were classified as "neoplastic epithelium absent" (NEA), and patients with neoplastic epithelium were classified as "neoplastic epithelium present" (NEP). The study observed NEA in 78 of 353 patients (22 %). Mucin was found in 28 of the patients with NEA. For low-grade appendiceal mucinous neoplasms and adenomas, the 5-year overall survival rate was 100 % for NEA and 84 % for NEP, and the 5-year recurrence-free survival rate was 100 % for NEA and 59 % for NEP. For appendiceal/colorectal adenocarcinomas (including tumors of the small intestine), the 5-year overall survival rate was 61 % for NEA and 38 % for NEP, and the 5-year recurrence-free survival rate was 60 % for NEA and 14 % for NEP. Carcinoembryonic antigen level, peritoneal cancer index, and completeness of the cytoreduction score were lower in patients with NEA. A substantial proportion of patients undergoing CRS and HIPEC have NEA. These patients have a favorable prognosis and a decreased risk of recurrence. Differences in patient selection can affect the proportion of NEA and hence explain differences in survival rates between reported series.

  3. CT angiography - arms and legs

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/007675.htm CT angiography - arms and legs To use the sharing features on this page, please enable JavaScript. CT angiography combines a CT scan with the injection ...

  4. Arms Sales: Congressional Review Process

    DTIC Science & Technology

    2015-12-17

    the Arms Export Control Act (AECA), Congress must be formally notified 30 calendar days before the Administration can take the final steps to...Commercially licensed arms sales also must be formally notified to Congress 30 calendar days before the export license is issued if they involve the sale...also be formally notified to Congress for review 30 days prior to the license for export being approved. In the case of proposed licences for such

  5. CCP Crew Access Arm Arrival

    NASA Image and Video Library

    2016-08-11

    A heavy-lift transport truck, carrying the Crew Access Arm for Space Launch Complex 41, travels along the road toward Complex 41 at Cape Canaveral Air Force Station in Florida. The arm will be installed on the Complex 41 Crew Access Tower. It will be used as a bridge by astronauts to board Boeing's CST-100 Starliner spacecraft as it stands on the launch pad atop a United Launch Alliance Atlas V rocket.

  6. CCP Crew Access Arm Arrival

    NASA Image and Video Library

    2016-08-11

    A heavy-lift transport truck, carrying the Crew Access Arm for Space Launch Complex 41, backs up toward Complex 41 at Cape Canaveral Air Force Station in Florida. The arm will be installed on the Complex 41 Crew Access Tower. It will be used as a bridge by astronauts to board Boeing's CST-100 Starliner spacecraft as it stands on the launch pad atop a United Launch Alliance Atlas V rocket.

  7. CCP Crew Access Arm Arrival

    NASA Image and Video Library

    2016-08-11

    A heavy-lift transport truck, carrying the Crew Access Arm for Space Launch Complex 41, departs from Oak Hill, Florida, and heads to NASA’s Kennedy Space Center in Florida. The arm will be installed on the Complex 41 Crew Access Tower at Cape Canaveral Air Force Station. It will be used as a bridge by astronauts to board Boeing's CST-100 Starliner spacecraft as it stands on the launch pad atop a United Launch Alliance Atlas V rocket.

  8. CCP Crew Access Arm Arrival

    NASA Image and Video Library

    2016-08-11

    A heavy-lift transport truck, carrying the Crew Access Arm for Space Launch Complex 41, arrives at Complex 41 at Cape Canaveral Air Force Station in Florida. The arm will be installed on the Complex 41 Crew Access Tower. It will be used as a bridge by astronauts to board Boeing's CST-100 Starliner spacecraft as it stands on the launch pad atop a United Launch Alliance Atlas V rocket.

  9. CCP Crew Access Arm Arrival

    NASA Image and Video Library

    2016-08-11

    A heavy-lift transport truck, carrying the Crew Access Arm for Space Launch Complex 41, passes through the entrance to NASA’s Kennedy Space Center in Florida. The arm will be installed on the Complex 41 Crew Access Tower at Cape Canaveral Air Force Station. It will be used as a bridge by astronauts to board Boeing's CST-100 Starliner spacecraft as it stands on the launch pad atop a United Launch Alliance Atlas V rocket.

  10. Brazilian Arms Production: Partial Dependence

    DTIC Science & Technology

    1988-09-01

    neighbors, before the Great Depression Brazil relied upon the export of primary commodities such as coffee, sugar and cocoa for its hard currency...24 Conclusions 26 Appendix 29 - VII - TABLES A.l. Brazilian arms exports and imports, 1968-86 30 A.2. Destination of...Embracr aircraft delivered outside of Brazil, 1975- 83 31 FIGURE 1. Brazilian arms exports and imports, 1968-86 25 IX - ACKNOWLEDGMENTS

  11. Absent movement-related cortical potentials in children with primary motor stereotypies.

    PubMed

    Houdayer, Elise; Walthall, Jessica; Belluscio, Beth A; Vorbach, Sherry; Singer, Harvey S; Hallett, Mark

    2014-08-01

    The underlying pathophysiologic mechanism for complex motor stereotypies in children is unknown, with hypotheses ranging from an arousal to a motor control disorder. Movement-related cortical potentials (MRCPs), representing the activation of cerebral areas involved in the generation of movements, precede and accompany self-initiated voluntary movements. The goal of this study was to compare cerebral activity associated with stereotypies to that seen with voluntary movements in children with primary complex motor stereotypies. Electroencephalographic (EEG) activity synchronized with video recording was recorded in 10 children diagnosed with primary motor stereotypies and 7 controls. EEG activity related to stereotypies and self-paced arm movements were analyzed for presence or absence of early or late MRCP, a steep negativity beginning about 1 second before the onset of a voluntary movement. Early MRCPs preceded self-paced arm movements in 8 of 10 children with motor stereotypies and in 6 of 7 controls. Observed MRCPs did not differ between groups. No MRCP was identified before the appearance of a complex motor stereotypy. Unlike voluntary movements, stereotypies are not preceded by MRCPs. This indicates that premotor areas are likely not involved in the preparation of these complex movements and suggests that stereotypies are initiated by mechanisms different from voluntary movements. Further studies are required to determine the site of the motor control abnormality within cortico-striatal-thalamo-cortical pathways and to identify whether similar findings would be found in children with secondary stereotypies. © 2013 International Parkinson and Movement Disorder Society.

  12. Absent movement-related cortical potentials in children with primary motor stereotypies

    PubMed Central

    Houdayer, Elise; Walthall, Jessica; Belluscio, Beth A.; Vorbach, Sherry; Singer, Harvey S.; Hallett, Mark

    2013-01-01

    Background The underlying pathophysiologic mechanism for complex motor stereotypies in children is unknown with hypotheses ranging from an arousal to a motor control disorder. Movement-related cortical potentials (MRCPs), representing the activation of cerebral areas involved in the generation of movements, precede and accompany self-initiated voluntary movements. The goal of this study was to compare cerebral activity associated with stereotypies to that seen with voluntary movements in children with primary complex motor stereotypies. Methods Electroencephalographic (EEG) activity synchronized with video recording was recorded in 10 children diagnosed with primary motor stereotypies and 7 controls. EEG activity related to stereotypies and self-paced arm movements were analyzed for presence or absence of early or late MRCP, a steep negativity beginning about one second before the onset of a voluntary movement. Results Early MRCPs preceded self-paced arm movements in 8 out of 10 children with motor stereotypies and in 6 out of 7 controls. Observed MRCPs did not differ between groups. No MRCP was identified before the appearance of a complex motor stereotypy. Conclusions Unlike voluntary movements, stereotypies are not preceded by MRCPs. This indicates that premotor areas are likely not involved in the preparation of these complex movements and suggests that stereotypies are initiated by mechanisms different from voluntary movements. Further studies are required to determine the site of the motor control abnormality within cortico-striatal-thalamo-cortical pathways and to identify whether similar findings would be found in children with secondary stereotypies. PMID:24259275

  13. On avoided words, absent words, and their application to biological sequence analysis.

    PubMed

    Almirantis, Yannis; Charalampopoulos, Panagiotis; Gao, Jia; Iliopoulos, Costas S; Mohamed, Manal; Pissis, Solon P; Polychronopoulos, Dimitris

    2017-01-01

    The deviation of the observed frequency of a word w from its expected frequency in a given sequence x is used to determine whether or not the word is avoided . This concept is particularly useful in DNA linguistic analysis. The value of the deviation of w , denoted by [Formula: see text], effectively characterises the extent of a word by its edge contrast in the context in which it occurs. A word w of length [Formula: see text] is a [Formula: see text]-avoided word in x if [Formula: see text], for a given threshold [Formula: see text]. Notice that such a word may be completely absent from x . Hence, computing all such words naïvely can be a very time-consuming procedure, in particular for large k . In this article, we propose an [Formula: see text]-time and [Formula: see text]-space algorithm to compute all [Formula: see text]-avoided words of length k in a given sequence of length n over a fixed-sized alphabet. We also present a time-optimal [Formula: see text]-time algorithm to compute all [Formula: see text]-avoided words (of any length) in a sequence of length n over an integer alphabet of size [Formula: see text]. In addition, we provide a tight asymptotic upper bound for the number of [Formula: see text]-avoided words over an integer alphabet and the expected length of the longest one. We make available an implementation of our algorithm. Experimental results, using both real and synthetic data, show the efficiency and applicability of our implementation in biological sequence analysis. The systematic search for avoided words is particularly useful for biological sequence analysis. We present a linear-time and linear-space algorithm for the computation of avoided words of length k in a given sequence x . We suggest a modification to this algorithm so that it computes all avoided words of x , irrespective of their length, within the same time complexity. We also present combinatorial results with regards to avoided words and absent words.

  14. Role of "Sural Sparing" Pattern (Absent/Abnormal Median and Ulnar with Present Sural SNAP) Compared to Absent/Abnormal Median or Ulnar with Normal Sural SNAP in Acute Inflammatory Demyelinating Polyneuropathy.

    PubMed

    Surpur, Spurthi Sunil; Govindarajan, Raghav

    2017-01-01

    Sural sparing defined as absent/abnormal median sensory nerve action potential (SNAP) amplitude or absent/abnormal ulnar SNAP amplitude with a normal sural SNAP amplitude is thought to be a marker for inflammatory demyelinating polyneuropathies. If sural sparing pattern specifically defined as absent/abnormal median and ulnar SNAP amplitude with normal sural SNAP amplitude (AMUNS) is sensitive and specific when compared with either absent/abnormal median and normal sural (AMNS) or absent/abnormal ulnar and normal sural (AUNS) for acute inflammatory demyelinating polyneuropathy (AIDP), chronic inflammatory demyelinating polyneuropathy (CIDP), select non-diabetic axonopathies (AXPs), and diabetic neuropathies (DNs). Retrospective analysis from 2001 to 2010 on all newly diagnosed AIDP, CIDP, select non-diabetic AXP, and DN. There were 20 AIDP and 23 CIDP. Twenty AXP and 50 DN patients between 2009 and 2010 were included as controls. AMUNS was seen in 65% of AIDP, 39% CIDP compared with 10% of AXP and 6% for DN with sensitivity of 51%, specificity of 92%, whereas the specificity of AMNS/AUNS was 73% and its sensitivity was 58%. If a patient has AMUNS they are >12 times more likely to have AIDP ( p  < 0.001). Sural sparing is highly specific but not sensitive when compared with either AMNS or AUNS in AIDP but does not add to sensitivity or specificity in CIDP.

  15. Impact of genetic variants on haematopoiesis in patients with thrombocytopenia absent radii (TAR) syndrome.

    PubMed

    Manukjan, Georgi; Bösing, Hendrik; Schmugge, Markus; Strauß, Gabriele; Schulze, Harald

    2017-11-01

    Thrombocytopenia absent radii (TAR) syndrome is clearly defined by the combination of radial aplasia and reduced platelet counts. The genetics of TAR syndrome has recently been resolved and comprises a microdeletion on Chromosome 1 including the RBM8A gene and a single nucleotide polymorphism (SNP) either at the 5' untranslated region (5'UTR) or within the first intron of RBM8A. Although phenotypically readily diagnosed after birth, the genetic determination of particular SNPs in TAR syndrome harbours valuable information to evaluate disease severity and treatment decisions. Here, we present clinical data in a cohort of 38 patients and observed that platelet counts in individuals with 5'UTR SNP are significantly lower compared to patients bearing the SNP in intron 1. Moreover, elevated haemoglobin values could only be assessed in patients with 5'UTR SNP whereas white blood cell count is unaffected, indicating that frequently observed anaemia in TAR patients could also be SNP-dependent whereas leucocytosis does not correlate with genetic background. However, this report on a large cohort provides an overview of important haematological characteristics in TAR patients, facilitating evaluation of the various traits in this disease and indicating the importance of genetic validation for TAR syndrome. © 2017 John Wiley & Sons Ltd.

  16. Expression of beta-dystroglycan is reduced or absent in many human carcinomas.

    PubMed

    Cross, S S; Lippitt, J; Mitchell, A; Hollingsbury, F; Balasubramanian, S P; Reed, M W R; Eaton, C; Catto, J W; Hamdy, F; Winder, S J

    2008-11-01

    Dystroglycan is an important structural and signalling protein that is expressed in most human cells. alpha-Dystroglycan has been investigated and found to be reduced in human cancers, but there is only one published study on the expression of beta-dystroglycan in human cancer and that was only on small numbers of breast and prostatic cancers. The aim was to conduct a comprehensive immunohistochemical survey of the expression of beta-dystroglycan in normal human tissues and common cancers. Triplicate tissue microarrays of 681 samples of normal human tissues and common cancers were stained using an antibody directed against the cytoplasmic component of beta-dystroglycan. beta-Dystroglycan was strongly expressed at the intercellular junctions and basement membranes of all normal human epithelia. Expression of beta-dystroglycan was absent or markedly reduced in 100% of oesophageal adenocarcinomas, 97% of colonic cancers, 100% of transitional cell carcinomas of the urothelium and 94% of breast cancers. In the breast cancers, the only tumours that showed any retention of beta-dystroglycan expression were small low-grade oestrogen receptor-positive tumours. The only cancers that showed retention of beta-dystroglycan expression were cutaneous basal cell carcinomas. There is loss or marked reduction of beta-dystroglycan expression (by immunohistochemistry) in the vast majority of human cancers surveyed. Since beta-dystroglycan is postulated to have a tumour suppressor effect, this loss may have important functional significance.

  17. Attenuated or absent HRV response to postural change in subjects with primary insomnia.

    PubMed

    Jiang, Xiao-ling; Zhang, Zheng-gang; Ye, Cui-ping; Lei, Ying; Wu, Lei; Zhang, Ying; Chen, Yuan-yuan; Xiao, Zhong-ju

    2015-03-01

    Previous studies have compared rest heart rate variability (HRV) between insomniacs and good sleepers, but the results have not been consistent. The altered HRV behavior in response to postural change was considered useful as another sensitive measure for evaluating the autonomic nervous function, however, to our knowledge, no study was found using HRV response to postural change in primary insomnia. Our study aimed to examine HRV response to postural change maneuver (PCM) in both primary insomniacs and controls between 22 and 39 years of age to gain insights into the characteristics of the autonomic nervous system (ANS) function in primary insomnia subjects. HRV was recorded for 5 min at seated rest, and then, the subjects quickly stood up from a seated position in up to 3s and remained standing for 15 min. HRV was recorded at the following times: seated rest and 0-5 min, 5-10 min and 10-15 min in the standing position. In primary insomnia subjects, attenuated or absent HRV response to postural change was identified, the increase in LF/HF ratio and the decrease in HF and SD1 from seated to standing were much slower than in the normal controls. In conclusion, this study provided evidence of the possible bi-directional relationship between insomnia and autonomic nervous system (ANS) function, which will move us closer to developing a new sensitive method for measuring autonomic impairment and early sympathetic damage in primary insomnia subjects. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Absent end diastolic flow of umbilical artery Doppler: pregnancy outcome in 62 cases.

    PubMed

    Poulain, P; Palaric, J C; Milon, J; Betremieux, P; Proudhon, J F; Signorelli, D; Grall, J Y; Giraud, J R

    1994-02-01

    We retrospectively studied the outcome of pregnancy in 62 cases of absent end diastolic flow (AEDF) of umbilical artery Doppler flow velocity waveform. The history of pregnancies revealed that nearly all were of high risk. Many cases presented cerebral (65%) or uterine (55.5%) Doppler flow abnormalities, or both (38%). We noted 10 fetal deaths and decided 7 pregnancy terminations. Malformation and chromosomal defect rate was 16%. We noted 44 (71%) live-births, a very high rate of cesarean section (86%), prematurity (75%), small for gestational age (39%). Forty-five percent of the neonates had a 1-min Apgar score under 7, which dropped to 27% at 5 min. Neonate mortality rate was 6.9% and the total mortality rate was 34% (21/62). Morbidity was significant (7 cases with severe morbidity, 2 cases with chromosomal abnormality of poor prognosis). We compared different sub-groups with a view to looking for some prenatal factors which predict poor neonatal outcome in case of AEDF.

  19. MAPK Target Sites of Eyes Absent Are Not Required for Eye Development or Survival in Drosophila

    PubMed Central

    Jusiak, Barbara; Abulimiti, Abuduaini; Haelterman, Nele; Chen, Rui; Mardon, Graeme

    2012-01-01

    Eyes absent (Eya) is a highly conserved transcription cofactor and protein phosphatase that plays an essential role in eye development and survival in Drosophila. Ectopic eye induction assays using cDNA transgenes have suggested that mitogen activated protein kinase (MAPK) activates Eya by phosphorylating it on two consensus target sites, S402 and S407, and that this activation potentiates the ability of Eya to drive eye formation. However, this mechanism has never been tested in normal eye development. In the current study, we generated a series of genomic rescue transgenes to investigate how loss- and gain-of-function mutations at these two MAPK target sites within Eya affect Drosophila survival and normal eye formation: eya+GR, the wild-type control; eyaSAGR, which lacks phosphorylation at the two target residues; and eyaSDEGR, which contains phosphomimetic amino acids at the same two residues. Contrary to the previous studies in ectopic eye development, all eya genomic transgenes tested rescue both eye formation and survival equally effectively. We conclude that, in contrast to ectopic eye formation, MAPK-mediated phosphorylation of Eya on S402 and S407 does not play a role in normal development. This is the first study in Drosophila to evaluate the difference in outcomes between genomic rescue and ectopic cDNA-based overexpression of the same gene. These findings indicate similar genomic rescue strategies may prove useful for re-evaluating other long-standing Drosophila developmental models. PMID:23251383

  20. 22 CFR 130.3 - Armed forces.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Armed forces. 130.3 Section 130.3 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS POLITICAL CONTRIBUTIONS, FEES AND COMMISSIONS § 130.3 Armed forces. Armed forces means the army, navy, marine, air force, or coast guard, as...

  1. 49 CFR 234.223 - Gate arm.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Gate arm. 234.223 Section 234.223 Transportation... Maintenance Standards § 234.223 Gate arm. Each gate arm, when in the downward position, shall extend across... clearly viewed by approaching highway users. Each gate arm shall start its downward motion not less than...

  2. 49 CFR 234.223 - Gate arm.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Gate arm. 234.223 Section 234.223 Transportation... SYSTEMS Maintenance, Inspection, and Testing Maintenance Standards § 234.223 Gate arm. Each gate arm, when... maintained in a condition sufficient to be clearly viewed by approaching highway users. Each gate arm shall...

  3. 49 CFR 234.223 - Gate arm.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Gate arm. 234.223 Section 234.223 Transportation... SYSTEMS Maintenance, Inspection, and Testing Maintenance Standards § 234.223 Gate arm. Each gate arm, when... maintained in a condition sufficient to be clearly viewed by approaching highway users. Each gate arm shall...

  4. 49 CFR 234.223 - Gate arm.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Gate arm. 234.223 Section 234.223 Transportation... Maintenance Standards § 234.223 Gate arm. Each gate arm, when in the downward position, shall extend across... clearly viewed by approaching highway users. Each gate arm shall start its downward motion not less than...

  5. 49 CFR 234.223 - Gate arm.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Gate arm. 234.223 Section 234.223 Transportation... SYSTEMS Maintenance, Inspection, and Testing Maintenance Standards § 234.223 Gate arm. Each gate arm, when... maintained in a condition sufficient to be clearly viewed by approaching highway users. Each gate arm shall...

  6. NASA's Asteroid Redirect Mission (ARM)

    NASA Astrophysics Data System (ADS)

    Abell, Paul; Mazanek, Dan; Reeves, David; Naasz, Bo; Cichy, Benjamin

    2015-11-01

    The National Aeronautics and Space Administration (NASA) is developing a robotic mission to visit a large near-Earth asteroid (NEA), collect a multi-ton boulder from its surface, and redirect it into a stable orbit around the Moon. Once returned to cislunar space in the mid-2020s, astronauts will explore the boulder and return to Earth with samples. This Asteroid Redirect Mission (ARM) is part of NASA’s plan to advance the technologies, capabilities, and spaceflight experience needed for a human mission to the Martian system in the 2030s. Subsequent human and robotic missions to the asteroidal material would also be facilitated by its return to cislunar space. Although ARM is primarily a capability demonstration mission (i.e., technologies and associated operations), there exist significant opportunities to advance our knowledge of small bodies in the synergistic areas of science, planetary defense, asteroidal resources and in-situ resource utilization (ISRU), and capability and technology demonstrations. In order to maximize the knowledge return from the mission, NASA is organizing an ARM Investigation Team, which is being preceded by the Formulation Assessment and Support Team. These teams will be comprised of scientists, technologists, and other qualified and interested individuals to help plan the implementation and execution of ARM. An overview of robotic and crewed segments of ARM, including the mission requirements, NEA targets, and mission operations, will be provided along with a discussion of the potential opportunities associated with the mission.

  7. The Asteroid Redirect Mission (ARM)

    NASA Technical Reports Server (NTRS)

    Abell, Paul

    2015-01-01

    The National Aeronautics and Space Administration (NASA) is developing a robotic mission to visit a large near-Earth asteroid (NEA), collect a multi-ton boulder from its surface, and redirect it into a stable orbit around the Moon. Once returned to cislunar space in the mid-2020s, astronauts will explore the boulder and return to Earth with samples. This Asteroid Redirect Mission (ARM) is part of NASA's plan to advance the technologies, capabilities, and spaceflight experience needed for a human mission to the Martian system in the 2030s. Subsequent human and robotic missions to the asteroidal material would also be facilitated by its return to cislunar space. Although ARM is primarily a capability demonstration mission (i.e., technologies and associated operations), there exist significant opportunities to advance our knowledge of small bodies in the synergistic areas of science, planetary defense, asteroidal resources and in-situ resource utilization (ISRU), and capability and technology demonstrations. In order to maximize the knowledge return from the mission, NASA is organizing an ARM Investigation Team, which is being preceded by the Formulation Assessment and Support Team. These teams will be comprised of scientists, technologists, and other qualified and interested individuals to help plan the implementation and execution of ARM. An overview of robotic and crewed segments of ARM, including the mission requirements, NEA targets, and mission operations, will be provided along with a discussion of the potential opportunities associated with the mission.

  8. Scanning ARM Cloud Radar Handbook

    SciTech Connect

    Widener, K; Bharadwaj, N; Johnson, K

    2012-06-18

    The scanning ARM cloud radar (SACR) is a polarimetric Doppler radar consisting of three different radar designs based on operating frequency. These are designated as follows: (1) X-band SACR (X-SACR); (2) Ka-band SACR (Ka-SACR); and (3) W-band SACR (W-SACR). There are two SACRs on a single pedestal at each site where SACRs are deployed. The selection of the operating frequencies at each deployed site is predominantly determined by atmospheric attenuation at the site. Because RF attenuation increases with atmospheric water vapor content, ARM's Tropical Western Pacific (TWP) sites use the X-/Ka-band frequency pair. The Southern Great Plains (SGP) and Northmore » Slope of Alaska (NSA) sites field the Ka-/W-band frequency pair. One ARM Mobile Facility (AMF1) has a Ka/W-SACR and the other (AMF2) has a X/Ka-SACR.« less

  9. Ergonomically neutral arm support system

    DOEpatents

    Siminovitch, Michael J; Chung, Jeffrey Y; Dellinges, Steven; Lafever, Robin E

    2005-08-02

    An ergonomic arm support system maintains a neutral position for the forearm. A mechanical support structure attached to a chair or other mounting structure supports the arms of a sitting or standing person. The system includes moving elements and tensioning elements to provide a dynamic balancing force against the forearms. The support structure is not fixed or locked in a rigid position, but is an active dynamic system that is maintained in equipoise by the continuous operation of the opposing forces. The support structure includes an armrest connected to a flexible linkage or articulated or pivoting assembly, which includes a tensioning element such as a spring. The pivoting assembly moves up and down, with the tensioning element providing the upward force that balances the downward force of the arm.

  10. Proprioceptive Interaction between the Two Arms in a Single-Arm Pointing Task.

    PubMed

    Kigawa, Kazuyoshi; Izumizaki, Masahiko; Tsukada, Setsuro; Hakuta, Naoyuki

    2015-01-01

    Proprioceptive signals coming from both arms are used to determine the perceived position of one arm in a two-arm matching task. Here, we examined whether the perceived position of one arm is affected by proprioceptive signals from the other arm in a one-arm pointing task in which participants specified the perceived position of an unseen reference arm with an indicator paddle. Both arms were hidden from the participant's view throughout the study. In Experiment 1, with both arms placed in front of the body, the participants received 70-80 Hz vibration to the elbow flexors of the reference arm (= right arm) to induce the illusion of elbow extension. This extension illusion was compared with that when the left arm elbow flexors were vibrated or not. The degree of the vibration-induced extension illusion of the right arm was reduced in the presence of left arm vibration. In Experiment 2, we found that this kinesthetic interaction between the two arms did not occur when the left arm was vibrated in an abducted position. In Experiment 3, the vibration-induced extension illusion of one arm was fully developed when this arm was placed at an abducted position, indicating that the brain receives increased proprioceptive input from a vibrated arm even if the arm was abducted. Our results suggest that proprioceptive interaction between the two arms occurs in a one-arm pointing task when the two arms are aligned with one another. The position sense of one arm measured using a pointer appears to include the influences of incoming information from the other arm when both arms were placed in front of the body and parallel to one another.

  11. Proprioceptive Interaction between the Two Arms in a Single-Arm Pointing Task

    PubMed Central

    Kigawa, Kazuyoshi; Izumizaki, Masahiko; Tsukada, Setsuro; Hakuta, Naoyuki

    2015-01-01

    Proprioceptive signals coming from both arms are used to determine the perceived position of one arm in a two-arm matching task. Here, we examined whether the perceived position of one arm is affected by proprioceptive signals from the other arm in a one-arm pointing task in which participants specified the perceived position of an unseen reference arm with an indicator paddle. Both arms were hidden from the participant’s view throughout the study. In Experiment 1, with both arms placed in front of the body, the participants received 70–80 Hz vibration to the elbow flexors of the reference arm (= right arm) to induce the illusion of elbow extension. This extension illusion was compared with that when the left arm elbow flexors were vibrated or not. The degree of the vibration-induced extension illusion of the right arm was reduced in the presence of left arm vibration. In Experiment 2, we found that this kinesthetic interaction between the two arms did not occur when the left arm was vibrated in an abducted position. In Experiment 3, the vibration-induced extension illusion of one arm was fully developed when this arm was placed at an abducted position, indicating that the brain receives increased proprioceptive input from a vibrated arm even if the arm was abducted. Our results suggest that proprioceptive interaction between the two arms occurs in a one-arm pointing task when the two arms are aligned with one another. The position sense of one arm measured using a pointer appears to include the influences of incoming information from the other arm when both arms were placed in front of the body and parallel to one another. PMID:26317518

  12. The interaction of flavivirus M protein with light chain Tctex-1 of human dynein plays a role in late stages of virus replication.

    PubMed

    Brault, Jean-Baptiste; Kudelko, Mateusz; Vidalain, Pierre-Olivier; Tangy, Frédéric; Desprès, Philippe; Pardigon, Nathalie

    2011-09-01

    The role of the membrane protein (prM/M) in flavivirus life cycle remains unclear. Here, we identified a cellular interactor to the 40-residue-long ectodomain of prM/M (ectoM) using a yeast two-hybrid screen against a human cDNA library and GST pull-down assays. We showed that dynein light chain Tctex-1 interacts with the ectoM of dengue 1-4, West Nile, and Japanese encephalitis flaviviruses. No interaction was found with yellow fever and tick-borne flaviviruses. This interaction is highly specific since a single amino-acid change in the ectoM abrogates the interaction with Tctex-1. To understand the role of this interaction, silencing of Tctex-1 using siRNA was performed prior to infection. A significant decrease in progeny production was observed for dengue and West Nile viruses. Silencing Tctex-1 inhibited the production of recombinant dengue subviral particles (RSPs). Thus Tctex-1 may play a role in late stages of viral replication through its interaction with the membrane protein. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Rab5 and its effector FHF contribute to neuronal polarity through dynein-dependent retrieval of somatodendritic proteins from the axon

    PubMed Central

    Guo, Xiaoli; Farías, Ginny G.; Mattera, Rafael; Bonifacino, Juan S.

    2016-01-01

    An open question in cell biology is how the general intracellular transport machinery is adapted to perform specialized functions in polarized cells such as neurons. Here we illustrate this adaptation by elucidating a role for the ubiquitous small GTPase Ras-related protein in brain 5 (Rab5) in neuronal polarity. We show that inactivation or depletion of Rab5 in rat hippocampal neurons abrogates the somatodendritic polarity of the transferrin receptor and several glutamate receptor types, resulting in their appearance in the axon. This loss of polarity is not caused primarily by increased transport from the soma to the axon but rather by decreased retrieval from the axon to the soma. Retrieval is also dependent on the Rab5 effector Fused Toes (FTS)–Hook–FTS and Hook-interacting protein (FHIP) (FHF) complex, which interacts with the minus-end–directed microtubule motor dynein and its activator dynactin to drive a population of axonal retrograde carriers containing somatodendritic proteins toward the soma. These findings emphasize the importance of both biosynthetic sorting and axonal retrieval for the polarized distribution of somatodendritic receptors at steady state. PMID:27559088

  14. Nocturnal polyuria is related to absent circadian rhythm of glomerular filtration rate.

    PubMed

    De Guchtenaere, A; Vande Walle, C; Van Sintjan, P; Raes, A; Donckerwolcke, R; Van Laecke, E; Hoebeke, P; Vande Walle, J

    2007-12-01

    Monosymptomatic nocturnal enuresis is frequently associated with nocturnal polyuria and low urinary osmolality during the night. Initial studies found decreased vasopressin levels associated with low urinary osmolality overnight. Together with the documented desmopressin response, this was suggestive of a primary role for vasopressin in the pathogenesis of enuresis in the absence of bladder dysfunction. Recent studies no longer confirm this primary role of vasopressin. Other pathogenetic factors such as disordered renal sodium handling, hypercalciuria, increased prostaglandins and/or osmotic excretion might have a role. So far, little attention has been given to abnormalities in the circadian rhythm of glomerular filtration rate. We evaluated the circadian rhythm of glomerular filtration rate and diuresis in children with desmopressin resistant monosymptomatic nocturnal enuresis and nocturnal polyuria. We evaluated 15 children (9 boys) 9 to 14 years old with monosymptomatic nocturnal enuresis and nocturnal polyuria resistant to desmopressin treatment. The control group consisted of 25 children (12 boys) 9 to 16 years old with monosymptomatic nocturnal enuresis without nocturnal polyuria. Compared to the control population, children with nocturnal polyuria lost their circadian rhythm not only for diuresis and sodium excretion but also for glomerular filtration rate. Patients with monosymptomatic nocturnal enuresis and nocturnal polyuria lack a normal circadian rhythm for diuresis and sodium excretion, and the circadian rhythm of glomerular filtration rate is absent. This absence of circadian rhythm of glomerular filtration rate and/or sodium handling cannot be explained by a primary role of vasopressin, but rather by a disorder in circadian rhythm of renal glomerular and/or tubular functions.

  15. Nicotine withdrawal-induced inattention is absent in alpha7 nAChR knockout mice

    PubMed Central

    Higa, K. K.; Grim, A.; Kamenski, M. E.; van Enkhuizen, J.; Zhou, X.; Li, K.; Naviaux, J. C.; Wang, L.; Naviaux, R. K.; Geyer, M. A.; Markou, A.; Young, J. W.

    2017-01-01

    Rationale Smoking is the leading cause of preventable death in the U.S., but quit attempts result in withdrawal-induced cognitive dysfunction and predicts relapse. Greater understanding of the neural mechanism(s) underlying these cognitive deficits is required to develop targeted treatments to aid quit attempts. Objectives We examined nicotine withdrawal-induced inattention in mice lacking the α7 nicotinic acetylcholine receptor (nAChR) using the 5-choice continuous performance test (5C-CPT). Methods Mice were trained in the 5C-CPT prior to osmotic minipump implantation containing saline or nicotine. Experiment 1 used 40 mg/kg/day nicotine treatment and tested C57BL/6 mice 4, 28, and 52 h after pump removal. Experiment 2 used 14 and 40 mg/kg/day nicotine treatment in α7 nAChR knockout (KO) and wildtype (WT) littermates tested 4 h after pump removal. Subsets of WT mice were sacrificed before and after pump removal to assess changes in receptor expression associated with nicotine administration and withdrawal. Results Nicotine withdrawal impaired attention in the 5C-CPT, driven by response inhibition and target detection deficits. The overall attentional deficit was absent in α7 nAChR KO mice despite response disinhibition in these mice. Synaptosomal glutamate mGluR5 and dopamine D4 receptor expression were reduced during chronic nicotine but increased during withdrawal, potentially contributing to cognitive deficits. Conclusions The α7 nAChR may underlie nicotine withdrawal-induced deficits in target detection but is not required for response disinhibition deficits. Alterations to the glutamatergic and dopaminergic pathways may also contribute to withdrawal-induced attentional deficits, providing novel targets to alleviate the cognitive symptoms of withdrawal during quit attempts. PMID:28243714

  16. Mismatch negativity of sad syllables is absent in patients with major depressive disorder.

    PubMed

    Pang, Xiaomei; Xu, Jing; Chang, Yi; Tang, Di; Zheng, Ya; Liu, Yanhua; Sun, Yiming

    2014-01-01

    Major depressive disorder (MDD) is an important and highly prevalent mental disorder characterized by anhedonia and a lack of interest in everyday activities. Additionally, patients with MDD appear to have deficits in various cognitive abilities. Although a number of studies investigating the central auditory processing of low-level sound features in patients with MDD have demonstrated that this population exhibits impairments in automatic processing, the influence of emotional voice processing has yet to be addressed. To explore the automatic processing of emotional prosodies in patients with MDD, we analyzed the ability to detect automatic changes using event-related potentials (ERPs). This study included 18 patients with MDD and 22 age- and sex-matched healthy controls. Subjects were instructed to watch a silent movie but to ignore the afferent acoustic emotional prosodies presented to both ears while continuous electroencephalographic activity was synchronously recorded. Prosodies included meaningless syllables, such as "dada" spoken with happy, angry, sad, or neutral tones. The mean amplitudes of the ERPs elicited by emotional stimuli and the peak latency of the emotional differential waveforms were analyzed. The sad MMN was absent in patients with MDD, whereas the happy and angry MMN components were similar across groups. The abnormal sad emotional MMN component was not significantly correlated with the HRSD-17 and HAMA scores, respectively. The data indicate that patients with MDD are impaired in their ability to automatically process sad prosody, whereas their ability to process happy and angry prosodies remains normal. The dysfunctional sad emotion-related MMN in patients with MDD were not correlated with depression symptoms. The blunted MMN of sad prosodies could be considered a trait of MDD.

  17. Differential effects of absent visual feedback control on gait variability during different locomotion speeds.

    PubMed

    Wuehr, M; Schniepp, R; Pradhan, C; Ilmberger, J; Strupp, M; Brandt, T; Jahn, K

    2013-01-01

    Healthy persons exhibit relatively small temporal and spatial gait variability when walking unimpeded. In contrast, patients with a sensory deficit (e.g., polyneuropathy) show an increased gait variability that depends on speed and is associated with an increased fall risk. The purpose of this study was to investigate the role of vision in gait stabilization by determining the effects of withdrawing visual information (eyes closed) on gait variability at different locomotion speeds. Ten healthy subjects (32.2 ± 7.9 years, 5 women) walked on a treadmill for 5-min periods at their preferred walking speed and at 20, 40, 70, and 80 % of maximal walking speed during the conditions of walking with eyes open (EO) and with eyes closed (EC). The coefficient of variation (CV) and fractal dimension (α) of the fluctuations in stride time, stride length, and base width were computed and analyzed. Withdrawing visual information increased the base width CV for all walking velocities (p < 0.001). The effects of absent visual information on CV and α of stride time and stride length were most pronounced during slow locomotion (p < 0.001) and declined during fast walking speeds. The results indicate that visual feedback control is used to stabilize the medio-lateral (i.e., base width) gait parameters at all speed sections. In contrast, sensory feedback control in the fore-aft direction (i.e., stride time and stride length) depends on speed. Sensory feedback contributes most to fore-aft gait stabilization during slow locomotion, whereas passive biomechanical mechanisms and an automated central pattern generation appear to control fast locomotion.

  18. Low road to arms control

    SciTech Connect

    Paine, C.

    1985-12-01

    In the absence of a strong presidential push for a meaningful agreement, the bureaucratic consensus-seeking process leading up to a US-Soviet summit can degenerate into a search for a least-common denominator that omits or otherwise protects each bureaucracy's sacred cows. Confusion among the agencies was the result of Reagan's signals that he would like to continue the arms build up at the same time he was publicly stating support for negotiations. This confusion leaves the administration's arms control policy-making in a state of contradiction, hyperbole, and bad faith. The author applies this appraisal to policies involving the Strategic Defense Initiative.

  19. The next great arms race

    SciTech Connect

    Klare, M.T.

    Fueled by dramatic economic growth, the nations of East and Southeast Asia are engaged in an arms race that shows every sign of accelerating. These countries are importing not only complex weapon systems but, more important, the technology with which to manufacture them. Since longstanding territorial and border disputes remain (most notably in the South China Sea) and the twin threats of China and Japan loom large, the potential for conflicts is great. Without arms control and regional security measures, the Pacific Rim could one day be the site of a major conflagration.

  20. The Chinese Communist Armed Forces.

    DTIC Science & Technology

    1974-01-01

    tepriorcosn \\ MAR 1 3 1981 C ~) AIR UNIVERSITY -4 MAXWELL AIR FORCE BASE, ALABAMA I z AU-I I "-- ’The Chinese Communist Armed Forces. Kenneth R. Whiting...AO-A096 28𔃾 DEPARTMENT OF STATE WASHINGTON DC OFFICE OF EXTERNAL--ETC F/6 S/ THE CH INESE C OMMUNIST ARMED FORCES. (U) vsif k.1974 K R WHITING FAR...1974 Directorate of Documentary Research Air University Institute for Professional Development Maxwell Air Force Base, Alabama "/" I;-) K II AIR

  1. ML Crew Access Arm Move

    NASA Image and Video Library

    2017-11-10

    A heavy-load transport truck carrying the Orion crew access arm passes the Vehicle Assembly Building on its way to the mobile launcher at NASA's Kennedy Space Center in Florida. The access arm will be installed at about the 274-foot level on the mobile launcher tower. It will rotate from its retracted position and interface with the Orion crew hatch location to provide entry to the Orion crew module. The Ground Systems Development and Operations Program is overseeing installation of umbilicals and launch accessories on the ML tower to prepare for Exploration Mission-1.

  2. ML Crew Access Arm Move

    NASA Image and Video Library

    2017-11-09

    The Orion crew access arm, secured on a stand, is being prepared for its move from a storage location at NASA's Kennedy Space Center in Florida, to the mobile launcher (ML) tower near the Vehicle Assembly Building at the center. The crew access arm will be installed at about the 274-foot level on the tower. It will rotate from its retracted position and interface with the Orion crew hatch location to provide entry to the Orion crew module. The Ground Systems Development and Operations Program is overseeing installation of umbilicals and launch accessories on the ML tower.

  3. ML Crew Access Arm Move

    NASA Image and Video Library

    2017-11-10

    A heavy-load transport truck carrying the Orion crew access arm makes its way toward the mobile launcher (ML) at NASA's Kennedy Space Center in Florida. The crew access arm will be installed at about the 274-foot level on the mobile launcher tower. It will rotate from its retracted position and interface with the Orion crew hatch location to provide entry to the Orion crew module. The Ground Systems Development and Operations Program is overseeing installation of umbilicals and launch accessories on the ML tower to prepare for Exploration Mission-1.

  4. ML Crew Access Arm Move

    NASA Image and Video Library

    2017-11-10

    A heavy-load transport truck carrying the Orion crew access arm nears the mobile launcher (ML) at NASA's Kennedy Space Center in Florida. The crew access arm will be installed at about the 274-foot level on the mobile launcher tower. It will rotate from its retracted position and interface with the Orion crew hatch location to provide entry to the Orion crew module. The Ground Systems Development and Operations Program is overseeing installation of umbilicals and launch accessories on the ML tower to prepare for Exploration Mission-1.

  5. CCP Crew Access Arm Arrival

    NASA Image and Video Library

    2016-08-11

    A heavy-lift transport truck, carrying the Crew Access Arm for Space Launch Complex 41, crosses the Haulover Canal Bridge on its way to the entrance of NASA’s Kennedy Space Center in Florida. The arm will be installed on the Complex 41 Crew Access Tower at Cape Canaveral Air Force Station. It will be used as a bridge by astronauts to board Boeing's CST-100 Starliner spacecraft as it stands on the launch pad atop a United Launch Alliance Atlas V rocket.

  6. ML Crew Access Arm Move

    NASA Image and Video Library

    2017-11-10

    The Orion crew access arm is secured on a flatbed transporter for its move from a storage location at NASA's Kennedy Space Center in Florida to the mobile launcher (ML) tower near the Vehicle Assembly Building at the center. The crew access arm will be installed at about the 274-foot level on the mobile launcher tower. It will rotate from its retracted position and interface with the Orion crew hatch location to provide entry to the Orion crew module. The Ground Systems Development and Operations Program is overseeing installation of umbilicals and launch accessories on the ML tower to prepare for Exploration Mission-1.

  7. Adulthood depression, anxiety, and trauma symptoms: a comparison of women with nonabusive, abusive, and absent father figures in childhood.

    PubMed

    Downs, William R; Rindels, Barb

    2004-12-01

    We collected data from 447 women (aged 18 or higher) from seven domestic violence programs and five substance use disorder treatment programs in a midwestern state. Women who reported a nonabusive natural/adoptive father or stepfather (N=185), abusive natural/adoptive father or stepfather (N=200), or absent father figure (N=40) were compared on a series of mental health measures with multivariate analysis of variance and pairwise post hoc comparisons using the Bonferroni test. Women with absent father figures were found to have significantly lower mean scores on the Beck Anxiety Inventory, Beck Depression Inventory, and Trauma Symptom Checklist-40 (TSC-40) than women with abusive fathers. There were no significant differences between women with absent father figures and women with nonabusive father figures on the Beck Anxiety Inventory, Beck Depression Inventory, and TSC-40. Implications for research, practice, and policy are discussed.

  8. Arms Control and National Security.

    ERIC Educational Resources Information Center

    Graham, Daniel O.

    1985-01-01

    From the Soviet perspective arms control agreements merely hold the United States in check while the Soviets, who don't feel bound by such agreements, obtain military advantages. The United States must move quickly to redress the strategic military balance that now favors the Soviets. We must emphasize areas like space. (RM)

  9. EDUCATION IN THE ARMED FORCES.

    ERIC Educational Resources Information Center

    GROVES, KENNETH J.; SHELBURNE, JAMES C.

    IN THIS SURVEY OF THE TRAINING OF ACTIVE DUTY ARMED FORCES, VARIOUS CATEGORIES ARE IDENTIFIED AND DISCUSSED--TRAINING AND EDUCATION OF ENLISTED MEN (INCLUDING SPECIALISTS AND POTENTIAL NONCOMMISSIONED OFFICERS), OFFICER TRAINING AND SPECIALIZED EDUCATION, PROFESSIONAL MILITARY EDUCATION, UNIT TRAINING, AND OFF-DUTY ACADEMIC AND VOCATIONAL…

  10. Amine templating effect absent in uranyl sulfates synthesized with 1,4-n-butyldiamine

    SciTech Connect

    Jouffret, Laurent J., E-mail: ljouffret@nd.edu; Wylie, Ernest M.; Burns, Peter C.

    2013-01-15

    Two new uranyl sulfates, (C{sub 4}H{sub 14}N{sub 2})[(UO{sub 2}){sub 2}(SO{sub 4}){sub 3}(H{sub 2}O)]{center_dot}2H{sub 2}O (NDUS2) and (C{sub 4}H{sub 14}N{sub 2})[(UO{sub 2})(SO{sub 4}){sub 2}(H{sub 2}O)]{center_dot}2H{sub 2}O (NDUS3), were synthesized and their crystal structures determined. NDUS2 was obtained in highly acidic media heat-treated at 373 K and subsequently maintained at 278 K until crystals formed after two months. NDUS3 results from the degradation of NDUS2 over the course of a few days. NDUS2 and NDUS3 crystallize in the monoclinic space group P2{sub 1}/n, a=10.9075(4) A, b=10.4513(4) A, c=17.7881(7) A, {beta}=97.908(2) Degree-Sign , V=2008.52(13) A{sup 3}, Z=4, at 140 K and a=8.8570(4) A,more » b=7.3299(3) A, c=20.4260(9) A, {beta}=95.140(2) Degree-Sign , V=1320.74(10) A{sup 3}, Z=4, at 140 K, respectively. The compounds contain interlayer 1,4-n-butyldiammonium cations that charge-balance the anionic structural units. - Graphical abstract: Amine templating effect absent in uranyl sulfates synthesized with 1,4-diaminobutane, as shown by the synthesis of two new uranyl sulfates, (C{sub 4}H{sub 14}N{sub 2})[(UO{sub 2}){sub 2}(SO{sub 4}){sub 3}(H{sub 2}O)]{center_dot}2H{sub 2}O (NDUS2) and (C{sub 4}H{sub 14}N{sub 2})[(UO{sub 2})(SO{sub 4}){sub 2}(H{sub 2}O)]{center_dot}2H{sub 2}O (NDUS3). Highlights: Black-Right-Pointing-Pointer Two layered uranyl sulfates were synthesized. Black-Right-Pointing-Pointer Amine molecules are located in the interlayers of the compounds. Black-Right-Pointing-Pointer No templating effect of the amine was observed. Black-Right-Pointing-Pointer Amine molecules are only charge balancing cations in the structures.« less

  11. Deficits of Semantic Control Produce Absent or Reverse Frequency Effects in Comprehension: Evidence from Neuropsychology and Dual Task Methodology

    ERIC Educational Resources Information Center

    Almaghyuli, Azizah; Thompson, Hannah; Lambon Ralph, Matthew A.; Jefferies, Elizabeth

    2012-01-01

    Patients with multimodal semantic impairment following stroke (referred to here as "semantic aphasia" or SA) fail to show the standard effects of frequency in comprehension tasks. Instead, they show absent or even "reverse" frequency effects: i.e., better understanding of less common words. In addition, SA is associated with poor regulatory…

  12. Blood pressure measurement: one arm or both arm?

    PubMed

    Kulkarni, Prasad K; Shekhar, Susheela; Reddy, B N; Nirmala, B C

    2011-09-01

    Guidelines for measuring blood pressure includes measurement of blood pressure on both arms but it is often ignored. Our case report aims at highlighting the need follow the guidelines. A 60 year old 59 kg weighing male asymptomatic patient without any comobidities was posted for bilateral inguinal hernia repair. The interarm blood pressure difference was discovered incidentally during his preanaesthetic evalution. On further evaluation patient was found to be having subclavian stenosis on left side which was asymptomatic. Intraoperative and post operative period was uneventful. Blood pressure measurement should be done in accordance with the stipulated guidelines. Inter arm blood pressure difference should be noted in all patients as not only for diagnosis and treatment of hypertension but also as a tool to diagnose asymptomatic peripheral vascular disesase.

  13. Curiosity Mars Rover Flexes its Robotic Arm

    NASA Image and Video Library

    2010-09-16

    Test operators in a clean room at NASA Jet Propulsion Laboratory monitor some of the first motions by the robotic arm on the Mars rover Curiosity after installation in August 2010. The arm is shown in a partially extended position.

  14. Overcoming Robot-Arm Joint Singularities

    NASA Technical Reports Server (NTRS)

    Barker, L. K.; Houck, J. A.

    1986-01-01

    Kinematic equations allow arm to pass smoothly through singular region. Report discusses mathematical singularities in equations of robotarm control. Operator commands robot arm to move in direction relative to its own axis system by specifying velocity in that direction. Velocity command then resolved into individual-joint rotational velocities in robot arm to effect motion. However, usual resolved-rate equations become singular when robot arm is straightened.

  15. Dual arm coordination and control

    NASA Technical Reports Server (NTRS)

    Hayati, Samad; Tso, Kam; Lee, Thomas

    1989-01-01

    A generalized master/slave technique and experimental results for coordinated control of two arms rigidly grasping an object is described. An interactive program has been developed to allow a user the flexibility to select appropriate control modes for a given experiment. This interface allows for control gain adjustments. The results of several experiments performed on this system to demonstrate its capabilities such as transporting an object with or without induced internal forces and movement of a constrained object are offered. The system is further developed to achieve a so-called shared control mode in which an operator specifies the free motion trajectory for a point on the object of manipulation via a joystick while the autonomous control system is used for coordination and control of the arms.

  16. Regenerator cross arm seal assembly

    DOEpatents

    Jackman, Anthony V.

    1988-01-01

    A seal assembly for disposition between a cross arm on a gas turbine engine block and a regenerator disc, the seal assembly including a platform coextensive with the cross arm, a seal and wear layer sealingly and slidingly engaging the regenerator disc, a porous and compliant support layer between the platform and the seal and wear layer porous enough to permit flow of cooling air therethrough and compliant to accommodate relative thermal growth and distortion, a dike between the seal and wear layer and the platform for preventing cross flow through the support layer between engine exhaust and pressurized air passages, and air diversion passages for directing unregenerated pressurized air through the support layer to cool the seal and wear layer and then back into the flow of regenerated pressurized air.

  17. Chaotic evolution of arms races

    NASA Astrophysics Data System (ADS)

    Tomochi, Masaki; Kono, Mitsuo

    1998-12-01

    A new set of model equations is proposed to describe the evolution of the arms race, by extending Richardson's model with special emphases that (1) power dependent defensive reaction or historical enmity could be a motive force to promote armaments, (2) a deterrent would suppress the growth of armaments, and (3) the defense reaction of one nation against the other nation depends nonlinearly on the difference in armaments between two. The set of equations is numerically solved to exhibit stationary, periodic, and chaotic behavior depending on the combinations of parameters involved. The chaotic evolution is realized when the economic situation of each country involved in the arms race is quite different, which is often observed in the real world.

  18. The eastern arm of the Midcontinent Rift: Progress and problems

    SciTech Connect

    Hinze, W.J.

    1994-04-01

    The extent and nature of the Midcontinent Rift System (MCR) was initially determined by potential-field mapping and extrapolation of geologic information from the Lake Superior region. Early interpretation suggested a rift origin which is well supported by deep crustal reflection seismic data and isotopic evidence from the related volcanic rocks that became available during the past decade. A rift origin of the eastern arm of the MCR was corroborated by sub-Phanerozoic drilling into the clastic sediment and volcanic rocks in the McClure-Sparks drill hole located on a massive anticlinal feature in the Precambrian rocks mapped by seismic reflection data. Subsequentmore » seismic profiling further detailed the character of the rift. However, these studies also indicate that the eastern arm is unlike the western, e.g., adjacent clastic rock basins are absent, late-stage compressional features are present, but definite evidence for high-angle reverse faulting is missing, and volcanic basins are not continuous. The termination of this arm of the rift also remains problematic. There is no direct evidence of the rift SE of the McClure-Sparks hole in central Michigan. Geophysical anomalies and deep drilling in the Howell anticline region suggest that the 1,100 Ma old rift is covered by Grenville-age thrusts. If the rift extends farther to the SE, its nature must have been altered by the Grenville orogeny. The hypothesized extension across Ohio east of the Grenville Front is unsupported by seismic reflection profiling and anomaly modeling. Grabens identified at the basement surface in Ohio and to the south are of unknown age, but appear to be more clearly related to late-stage Grenville activity and/or continuation of Eocambrian rifts of the Mississippi Embayment.« less

  19. MAP4-regulated dynein-dependent trafficking of BTN3A1 controls the TBK1–IRF3 signaling axis

    PubMed Central

    Seo, Minji; Lee, Seong-Ok; Kim, Ji-Hoon; Hong, Yujin; Kim, Seongchan; Kim, Yeumin; Min, Dal-Hee; Kong, Young-Yun; Shin, Jinwook; Ahn, Kwangseog

    2016-01-01

    The innate immune system detects viral nucleic acids and induces type I interferon (IFN) responses. The RNA- and DNA-sensing pathways converge on the protein kinase TANK-binding kinase 1 (TBK1) and the transcription factor IFN-regulatory factor 3 (IRF3). Activation of the IFN signaling pathway is known to trigger the redistribution of key signaling molecules to punctate perinuclear structures, but the mediators of this spatiotemporal regulation have yet to be defined. Here we identify butyrophilin 3A1 (BTN3A1) as a positive regulator of nucleic acid-mediated type I IFN signaling. Depletion of BTN3A1 inhibits the cytoplasmic nucleic acid- or virus-triggered activation of IFN-β production. In the resting state, BTN3A1 is constitutively associated with TBK1. Stimulation with nucleic acids induces the redistribution of the BTN3A1–TBK1 complex to the perinuclear region, where BTN3A1 mediates the interaction between TBK1 and IRF3, leading to the phosphorylation of IRF3. Furthermore, we show that microtubule-associated protein 4 (MAP4) controls the dynein-dependent transport of BTN3A1 in response to nucleic acid stimulation, thereby identifying MAP4 as an upstream regulator of BTN3A1. Thus, the depletion of either MAP4 or BTN3A1 impairs cytosolic DNA- or RNA-mediated type I IFN responses. Our findings demonstrate a critical role for MAP4 and BTN3A1 in the spatiotemporal regulation of TBK1, a central player in the intracellular nucleic acid-sensing pathways involved in antiviral signaling. PMID:27911820

  20. The DOE ARM Aerial Facility

    SciTech Connect

    Schmid, Beat; Tomlinson, Jason M.; Hubbe, John M.

    2014-05-01

    The Department of Energy Atmospheric Radiation Measurement (ARM) Program is a climate research user facility operating stationary ground sites that provide long-term measurements of climate relevant properties, mobile ground- and ship-based facilities to conduct shorter field campaigns (6-12 months), and the ARM Aerial Facility (AAF). The airborne observations acquired by the AAF enhance the surface-based ARM measurements by providing high-resolution in-situ measurements for process understanding, retrieval-algorithm development, and model evaluation that are not possible using ground- or satellite-based techniques. Several ARM aerial efforts were consolidated into the AAF in 2006. With the exception of a small aircraft used for routinemore » measurements of aerosols and carbon cycle gases, AAF at the time had no dedicated aircraft and only a small number of instruments at its disposal. In this "virtual hangar" mode, AAF successfully carried out several missions contracting with organizations and investigators who provided their research aircraft and instrumentation. In 2009, AAF started managing operations of the Battelle-owned Gulfstream I (G-1) large twin-turboprop research aircraft. Furthermore, the American Recovery and Reinvestment Act of 2009 provided funding for the procurement of over twenty new instruments to be used aboard the G-1 and other AAF virtual-hangar aircraft. AAF now executes missions in the virtual- and real-hangar mode producing freely available datasets for studying aerosol, cloud, and radiative processes in the atmosphere. AAF is also engaged in the maturation and testing of newly developed airborne sensors to help foster the next generation of airborne instruments.« less

  1. Dual arm master controller development

    NASA Technical Reports Server (NTRS)

    Kuban, D. P.; Perkins, G. S.

    1985-01-01

    The advanced servomanipulator (ASM) slave was designed with an anthropomorphic stance gear/torque tube power drives, and modular construction. These features resulted in increased inertia, friction, and backlash relative to tape driven manipulators. Studies were performed which addressed to human factor design and performance tradeoffs associated with the corresponding master controller best suited for the ASM. The results of these studies, as well as the conceptual design of the dual arm master controller, are presented.

  2. 33 CFR 154.510 - Loading arms.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Loading arms. 154.510 Section 154... FACILITIES TRANSFERRING OIL OR HAZARDOUS MATERIAL IN BULK Equipment Requirements § 154.510 Loading arms. (a) Each mechanical loading arm used for transferring oil or hazardous material and placed into service...

  3. 33 CFR 154.510 - Loading arms.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Loading arms. 154.510 Section 154... FACILITIES TRANSFERRING OIL OR HAZARDOUS MATERIAL IN BULK Equipment Requirements § 154.510 Loading arms. (a) Each mechanical loading arm used for transferring oil or hazardous material and placed into service...

  4. 33 CFR 154.510 - Loading arms.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Loading arms. 154.510 Section 154... FACILITIES TRANSFERRING OIL OR HAZARDOUS MATERIAL IN BULK Equipment Requirements § 154.510 Loading arms. (a) Each mechanical loading arm used for transferring oil or hazardous material and placed into service...

  5. Arm Tremor, Tardive Dyskinesia, and Mental Retardation.

    ERIC Educational Resources Information Center

    van Emmerik, R. E. A.; And Others

    1993-01-01

    The arm tremor of adults (n=32) diagnosed as having mental retardation and/or tardive dyskinesia was examined through an analysis of the acceleration properties of several arm postures. The degree of arm acceleration was increased in all subjects compared to a control group without mental retardation. Effects of neuroleptic medication were noted.…

  6. Teaching about Reversing the Arms Race.

    ERIC Educational Resources Information Center

    Melman, Seymour

    1982-01-01

    The scarcity of college courses dealing with disarmament is noted, and educators are urged to address the question of arms limitation. Military and economic factors which limit the ability of the United States to continue the arms race are listed, and plans for reversing the arms race are discussed. (PP)

  7. The MVACS Robotic Arm Camera

    NASA Astrophysics Data System (ADS)

    Keller, H. U.; Hartwig, H.; Kramm, R.; Koschny, D.; Markiewicz, W. J.; Thomas, N.; Fernades, M.; Smith, P. H.; Reynolds, R.; Lemmon, M. T.; Weinberg, J.; Marcialis, R.; Tanner, R.; Boss, B. J.; Oquest, C.; Paige, D. A.

    2001-08-01

    The Robotic Arm Camera (RAC) is one of the key instruments newly developed for the Mars Volatiles and Climate Surveyor payload of the Mars Polar Lander. This lightweight instrument employs a front lens with variable focus range and takes images at distances from 11 mm (image scale 1:1) to infinity. Color images with a resolution of better than 50 μm can be obtained to characterize the Martian soil. Spectral information of nearby objects is retrieved through illumination with blue, green, and red lamp sets. The design and performance of the camera are described in relation to the science objectives and operation. The RAC uses the same CCD detector array as the Surface Stereo Imager and shares the readout electronics with this camera. The RAC is mounted at the wrist of the Robotic Arm and can characterize the contents of the scoop, the samples of soil fed to the Thermal Evolved Gas Analyzer, the Martian surface in the vicinity of the lander, and the interior of trenches dug out by the Robotic Arm. It can also be used to take panoramic images and to retrieve stereo information with an effective baseline surpassing that of the Surface Stereo Imager by about a factor of 3.

  8. High precision detector robot arm system

    SciTech Connect

    Shu, Deming; Chu, Yong

    A method and high precision robot arm system are provided, for example, for X-ray nanodiffraction with an X-ray nanoprobe. The robot arm system includes duo-vertical-stages and a kinematic linkage system. A two-dimensional (2D) vertical plane ultra-precision robot arm supporting an X-ray detector provides positioning and manipulating of the X-ray detector. A vertical support for the 2D vertical plane robot arm includes spaced apart rails respectively engaging a first bearing structure and a second bearing structure carried by the 2D vertical plane robot arm.

  9. The confidence-accuracy relationship in eyewitness identification: effects of lineup instructions, foil similarity, and target-absent base rates.

    PubMed

    Brewer, Neil; Wells, Gary L

    2006-03-01

    Discriminating accurate from mistaken eyewitness identifications is a major issue facing criminal justice systems. This study examined whether eyewitness confidence assists such decisions under a variety of conditions using a confidence-accuracy (CA) calibration approach. Participants (N = 1,200) viewed a simulated crime and attempted 2 separate identifications from 8-person target-present or target-absent lineups. Confidence and accuracy were calibrated for choosers (but not nonchoosers) for both targets under all conditions. Lower overconfidence was associated with higher diagnosticity, lower target-absent base rates, and shorter identification latencies. Although researchers agree that courtroom expressions of confidence are uninformative, our findings indicate that confidence assessments obtained immediately after a positive identification can provide a useful guide for investigators about the likely accuracy of an identification.

  10. The Asteroid Redirect Mission (ARM)

    NASA Astrophysics Data System (ADS)

    Abell, Paul; Gates, Michele; Johnson, Lindley; Chodas, Paul; Mazanek, Dan; Reeves, David; Ticker, Ronald

    2016-07-01

    To achieve its long-term goal of sending humans to Mars, the National Aeronautics and Space Administration (NASA) plans to proceed in a series of incrementally more complex human spaceflight missions. Today, human flight experience extends only to Low-Earth Orbit (LEO), and should problems arise during a mission, the crew can return to Earth in a matter of minutes to hours. The next logical step for human spaceflight is to gain flight experience in the vicinity of the Moon. These cis-lunar missions provide a "proving ground" for the testing of systems and operations while still accommodating an emergency return path to the Earth that would last only several days. Cis-lunar mission experience will be essential for more ambitious human missions beyond the Earth-Moon system, which will require weeks, months, or even years of transit time. In addition, NASA has been given a Grand Challenge to find all asteroid threats to human populations and know what to do about them. Obtaining knowledge of asteroid physical properties combined with performing technology demonstrations for planetary defense provide much needed information to address the issue of future asteroid impacts on Earth. Hence the combined objectives of human exploration and planetary defense give a rationale for the Asteroid Re-direct Mission (ARM). Mission Description: NASA's ARM consists of two mission segments: 1) the Asteroid Redirect Robotic Mission (ARRM), the first robotic mission to visit a large (greater than ~100 m diameter) near-Earth asteroid (NEA), collect a multi-ton boulder from its surface along with regolith samples, demonstrate a planetary defense technique, and return the asteroidal material to a stable orbit around the Moon; and 2) the Asteroid Redirect Crewed Mission (ARCM), in which astronauts will take the Orion capsule to rendezvous and dock with the robotic vehicle, conduct multiple extravehicular activities to explore the boulder, and return to Earth with samples. NASA's proposed

  11. Differences in sexual attitudes and likeliness of sexual behaviors of black lower-socioeconomic father-present vs. father-absent female adolescents.

    PubMed

    Eberhardt, C A; Schill, T

    1984-01-01

    This study compared sexual permissiveness attitudes and likely behaviors of father-absent vs. father-present black, lower-socioeconomic female adolescents. Father-absent subjects were not found to be more sexually permissive in reported likely behavior or attitude than father-present subjects. However, the father-absent group was found to have significantly greater inconsistency between behavioral and attitudinal scores in which the reported behavior was more permissive than the reported attitude. Finally, within the father-absent group, those subjects whose fathers became absent before they were five years old, were found to have a significantly higher need for social approval than subjects whose fathers became absent after they were five years old. The implications of these results are discussed.

  12. NASA's Asteroid Redirect Mission (ARM)

    NASA Technical Reports Server (NTRS)

    Abell, P. A.; Mazanek, D. D.; Reeves, D. M.; Chodas, P. W.; Gates, M. M.; Johnson, L. N.; Ticker, R. L.

    2017-01-01

    Mission Description and Objectives: NASA's Asteroid Redirect Mission (ARM) consists of two mission segments: 1) the Asteroid Redirect Robotic Mission (ARRM), a robotic mission to visit a large (greater than approximately 100 meters diameter) near-Earth asteroid (NEA), collect a multi-ton boulder from its surface along with regolith samples, and return the asteroidal material to a stable orbit around the Moon; and 2) the Asteroid Redirect Crewed Mission (ARCM), in which astronauts will explore and investigate the boulder and return to Earth with samples. The ARRM is currently planned to launch at the end of 2021 and the ARCM is scheduled for late 2026.

  13. C-arm rotation encoding with accelerometers.

    PubMed

    Grzeda, Victor; Fichtinger, Gabor

    2010-07-01

    Fluoroscopic C-arms are being incorporated in computer-assisted interventions in increasing number. For these applications to work, the relative poses of imaging must be known. To find the pose, tracking methods such as optical cameras, electromagnetic trackers, and radiographic fiducials have been used-all hampered by significant shortcomings. We propose to recover the rotational pose of the C-arm using the angle-sensing ability of accelerometers, by exploiting the capability of the accelerometer to measure tilt angles. By affixing the accelerometer to a C-arm, the accelerometer tracks the C-arm pose during rotations of the C-arm. To demonstrate this concept, a C-arm analogue was constructed with a webcam device affixed to the C-arm model to mimic X-ray imaging. Then, measuring the offset between the accelerometer angle readings to the webcam pose angle, an angle correction equation (ACE) was created to properly tracking the C-arm rotational pose. Several tests were performed on the webcam C-arm model using the ACEs to tracking the primary and secondary angle rotations of the model. We evaluated the capability of linear and polynomial ACEs to tracking the webcam C-arm pose angle for different rotational scenarios. The test results showed that the accelerometer could track the pose of the webcam C-arm model with an accuracy of less than 1.0 degree. The accelerometer was successful in sensing the C-arm's rotation with clinically adequate accuracy in the C-arm webcam model.

  14. Ophthalmological OCT measuring arm design

    NASA Astrophysics Data System (ADS)

    Xu, Xiaonan; Gao, Jiansong; Guo, Jihua; Xue, Ping

    2002-06-01

    This paper presents a novel ophthamological optical coherence tomography detecting instrument that we design and introduces measuring arm emphatically. For the glaucoma is very common in the orient, this system can achieve both the eyeground detection and the canthus detection. And it combines the cranny lamp's conventional detection with optical coherence tomography. In order to gain the best resolution and the largest scanning range in the OCT detection, we find the optical system should obey these principles in the measuring arm design: (i) the parallel light from the collimator goes through the lens and focuses on the slot of the cranny lamp. The movement of the scanning point produced by the scanner is carrying on along the slot. (Ii) In the whole light route, the scanner images on the laser object lens of the OCT. The center light of the infrared goes through the center of the object lens all the time. Considering all the system, this design has a longitudinal resolution of 15micrometers , and a transverse resolution of 20micrometers at imaging velocity of 4 frames per second.

  15. NIR small arms muzzle flash

    NASA Astrophysics Data System (ADS)

    Montoya, Joseph; Kennerly, Stephen; Rede, Edward

    2010-04-01

    Utilization of Near-Infrared (NIR) spectral features in a muzzle flash will allow for small arms detection using low cost silicon (Si)-based imagers. Detection of a small arms muzzle flash in a particular wavelength region is dependent on the intensity of that emission, the efficiency of source emission transmission through the atmosphere, and the relative intensity of the background scene. The NIR muzzle flash signature exists in the relatively large Si spectral response wavelength region of 300 nm-1100 nm, which allows for use of commercial-off-the-shelf (COTS) Si-based detectors. The alkali metal origin of the NIR spectral features in the 7.62 × 39-mm round muzzle flash is discussed, and the basis for the spectral bandwidth is examined, using a calculated Voigt profile. This report will introduce a model of the 7.62 × 39-mm NIR muzzle flash signature based on predicted source characteristics. Atmospheric limitations based on NIR spectral regions are investigated in relation to the NIR muzzle flash signature. A simple signal-to-clutter ratio (SCR) metric is used to predict sensor performance based on a model of radiance for the source and solar background and pixel registered image subtraction.

  16. [Arm rehabilitation : Current concepts and therapeutic options].

    PubMed

    Platz, T; Schmuck, L

    2016-10-01

    Arm paralysis after a stroke is a major cause of impairment. Presentation of therapeutic options and the efficacy in arm rehabilitation after stroke. Based on a systematic critical appraisal of randomized controlled trials (RCT) the therapeutic procedures for arm paralysis after stroke in the context of their effectiveness are introduced, including robotic therapy, mirror therapy, constraint-induced movement therapy (CIMT), arm basis training, arm ability training, neuromuscular electrical stimulation, bilateral and task-specific training, mental training and transcranial stimulation techniques, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). Several therapeutic procedures with proven efficacy are currently available for arm rehabilitation after stroke. Their differential indications are presented and associated with conclusions for clinical practice.

  17. Arms races between and within species.

    PubMed

    Dawkins, R; Krebs, J R

    1979-09-21

    An adaptation in one lineage (e.g. predators) may change the selection pressure on another lineage (e.g. prey), giving rise to a counter-adaptation. If this occurs reciprocally, an unstable runaway escalation or 'arms race' may result. We discuss various factors which might give one side an advantage in an arms race. For example, a lineage under strong selection may out-evolve a weakly selected one (' the life-dinner principle'). We then classify arms races in two independent ways. They may be symmetric or asymmetric, and they may be interspecific or intraspecific. Our example of an asymmetric interspecific arms race is that between brood parasites and their hosts. The arms race concept may help to reduce the mystery of why cuckoo hosts are so good at detecting cuckoo eggs, but so bad at detecting cuckoo nestlings. The evolutionary contest between queen and worker ants over relative parental investment is a good example of an intraspecific asymmetric arms race. Such cases raise special problems because the participants share the same gene pool. Interspecific symmetric arms races are unlikely to be important, because competitors tend to diverge rather than escalate competitive adaptations. Intraspecific symmetric arms races, exemplified by adaptations for male-male competition, may underlie Cope's Rule and even the extinction of lineages. Finally we consider ways in which arms races can end. One lineage may drive the other to extinction; one may reach an optimum, thereby preventing the other from doing so; a particularly interesting possibility, exemplified by flower-bee coevolution, is that both sides may reach a mutual local optimum; lastly, arms races may have no stable and but may cycle continuously. We do not wish necessarily to suggest that all, or even most, evolutionary change results from arms races, but we do suggest that the arms race concept may help to resolve three long-standing questions in evolutionary theory.

  18. 32 CFR 935.134 - Arm signals.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 6 2013-07-01 2013-07-01 false Arm signals. 935.134 Section 935.134 National... WAKE ISLAND CODE Motor Vehicle Code § 935.134 Arm signals. (a) Any person operating a motor vehicle and... signal for a turn or stop is made by fully extending the left arm as follows: (1) Left turn—extend left...

  19. 32 CFR 935.134 - Arm signals.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 6 2012-07-01 2012-07-01 false Arm signals. 935.134 Section 935.134 National... WAKE ISLAND CODE Motor Vehicle Code § 935.134 Arm signals. (a) Any person operating a motor vehicle and... signal for a turn or stop is made by fully extending the left arm as follows: (1) Left turn—extend left...

  20. 32 CFR 935.134 - Arm signals.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 6 2014-07-01 2014-07-01 false Arm signals. 935.134 Section 935.134 National... WAKE ISLAND CODE Motor Vehicle Code § 935.134 Arm signals. (a) Any person operating a motor vehicle and... signal for a turn or stop is made by fully extending the left arm as follows: (1) Left turn—extend left...

  1. Differences in Sexual Attitudes and Likeliness of Sexual Behaviors of Black Lower-Socioeconomic Father-Present vs. Father-Absent Female Adolescents.

    ERIC Educational Resources Information Center

    Eberhardt, Carolyn A.; Schill, Thomas

    1984-01-01

    Compared sexual permissiveness attitudes and likely behaviors of father-absent vs. father-present Black, lower-socioeconomic female adolescents (N=100). Father-absent subjects were not found to be more sexually permissive, but had significantly greater inconsistency between behavioral and attitudinal scores in which the reported behavior was more…

  2. Comparison of Smoking, Drinking, and Marijuana Use between Students Present or Absent on the Day of a School-Based Survey

    ERIC Educational Resources Information Center

    Bovet, Pascal; Viswanathan, Bharathi; Faeh, David; Warren, Wick

    2006-01-01

    The aim of this population-based survey was to compare the prevalence of selected risk behaviors between students present or absent on the day of a school-based survey. The study population was a representative sample of all students of secondary schools in the Seychelles (Indian Ocean). Students absent on the day of the survey were traced and…

  3. Conflict, famine and the arms trade.

    PubMed

    Judd, F

    1995-01-01

    Armed conflict has had horrendous humanitarian effects, causing 22 million deaths, over 80 per cent of them civilian, since 1945 and resulting today in 19 million refugees and 24 million displaced persons. War results in economic collapse, and high levels of military spending decrease regional stability. Benefits to the producers are limited or negative and developed countries should diversify away from arms production. There is a need for greater awareness in the developed countries, an end to the secrecy besetting the arms trade, and restructuring of the industry. A Code of Conduct governing arms exports is proposed.

  4. Quantifying arm nonuse in individuals poststroke.

    PubMed

    Han, Cheol E; Kim, Sujin; Chen, Shuya; Lai, Yi-Hsuan; Lee, Jeong-Yoon; Osu, Rieko; Winstein, Carolee J; Schweighofer, Nicolas

    2013-06-01

    Arm nonuse, defined as the difference between what the individual can do when constrained to use the paretic arm and what the individual does when given a free choice to use either arm, has not yet been quantified in individuals poststroke. (1) To quantify nonuse poststroke and (2) to develop and test a novel, simple, objective, reliable, and valid instrument, the Bilateral Arm Reaching Test (BART), to quantify arm use and nonuse poststroke. First, we quantify nonuse with the Quality of Movement (QOM) subscale of the Actual Amount of Use Test (AAUT) by subtracting the AAUT QOM score in the spontaneous use condition from the AAUT QOM score in a subsequent constrained use condition. Second, we quantify arm use and nonuse with BART by comparing reaching performance to visual targets projected over a 2D horizontal hemi-work space in a spontaneous-use condition (in which participants are free to use either arm at each trial) with reaching performance in a constrained-use condition. All participants (N = 24) with chronic stroke and with mild to moderate impairment exhibited nonuse with the AAUT QOM. Nonuse with BART had excellent test-retest reliability and good external validity. BART is the first instrument that can be used repeatedly and practically in the clinic to quantify the effects of neurorehabilitation on arm use and nonuse and in the laboratory for advancing theoretical knowledge about the recovery of arm use and the development of nonuse and "learned nonuse" after stroke.

  5. Absent husbands, single wives: success, domesticity, and seminuclear families in the nineteenth-century Great Lakes world.

    PubMed

    Nutting, P Bradley

    2010-01-01

    The industrial and transportation revolutions of nineteenth-century America separated work from home (at least for the growing middle class) and intensified the development of masculine and feminine spheres devoted to success and domesticity, respectively. This development tended to reduce the husband's traditional patriarchal roles to that of provider only, while leaving the wife and mother with enhanced authority over household management and child rearing, a development with consequences for feminism. This article examines two extreme cases of separation of work from home: absent husbands, respected professional men, who left their wives alone for months or years and, while they provided financial support, surrendered all household authority to "single" wives.

  6. Discovery of common sequences absent in the human reference genome using pooled samples from next generation sequencing.

    PubMed

    Liu, Yu; Koyutürk, Mehmet; Maxwell, Sean; Xiang, Min; Veigl, Martina; Cooper, Richard S; Tayo, Bamidele O; Li, Li; LaFramboise, Thomas; Wang, Zhenghe; Zhu, Xiaofeng; Chance, Mark R

    2014-08-16

    Sequences up to several megabases in length have been found to be present in individual genomes but absent in the human reference genome. These sequences may be common in populations, and their absence in the reference genome may indicate rare variants in the genomes of individuals who served as donors for the human genome project. As the reference genome is used in probe design for microarray technology and mapping short reads in next generation sequencing (NGS), this missing sequence could be a source of bias in functional genomic studies and variant analysis. One End Anchor (OEA) and/or orphan reads from paired-end sequencing have been used to identify novel sequences that are absent in reference genome. However, there is no study to investigate the distribution, evolution and functionality of those sequences in human populations. To systematically identify and study the missing common sequences (micSeqs), we extended the previous method by pooling OEA reads from large number of individuals and applying strict filtering methods to remove false sequences. The pipeline was applied to data from phase 1 of the 1000 Genomes Project. We identified 309 micSeqs that are present in at least 1% of the human population, but absent in the reference genome. We confirmed 76% of these 309 micSeqs by comparison to other primate genomes, individual human genomes, and gene expression data. Furthermore, we randomly selected fifteen micSeqs and confirmed their presence using PCR validation in 38 additional individuals. Functional analysis using published RNA-seq and ChIP-seq data showed that eleven micSeqs are highly expressed in human brain and three micSeqs contain transcription factor (TF) binding regions, suggesting they are functional elements. In addition, the identified micSeqs are absent in non-primates and show dynamic acquisition during primate evolution culminating with most micSeqs being present in Africans, suggesting some micSeqs may be important sources of human

  7. Robotic Arm Manipulation Laboratory With a Six Degree of Freedom JACO Arm

    DTIC Science & Technology

    2015-12-01

    MANIPULATION LABORATORY WITH A SIX DEGREE OF FREEDOM JACO ARM by Ronald H. Palacios December 2015 Thesis Advisor: Richard M. Harkins Second...TYPE AND DATES COVERED Master’s thesis 4. TITLE AND SUBTITLE ROBOTIC ARM MANIPULATION LABORATORY WITH A SIX DEGREE OF FREEDOM JACO ARM 5. FUNDING...distribution is unlimited 12b. DISTRIBUTION CODE 13. ABSTRACT (maximum 200 words) The JACO six degree of freedom robotic arm and associated software

  8. Cortical Spiking Network Interfaced with Virtual Musculoskeletal Arm and Robotic Arm

    PubMed Central

    Dura-Bernal, Salvador; Zhou, Xianlian; Neymotin, Samuel A.; Przekwas, Andrzej; Francis, Joseph T.; Lytton, William W.

    2015-01-01

    Embedding computational models in the physical world is a critical step towards constraining their behavior and building practical applications. Here we aim to drive a realistic musculoskeletal arm model using a biomimetic cortical spiking model, and make a robot arm reproduce the same trajectories in real time. Our cortical model consisted of a 3-layered cortex, composed of several hundred spiking model-neurons, which display physiologically realistic dynamics. We interconnected the cortical model to a two-joint musculoskeletal model of a human arm, with realistic anatomical and biomechanical properties. The virtual arm received muscle excitations from the neuronal model, and fed back proprioceptive information, forming a closed-loop system. The cortical model was trained using spike timing-dependent reinforcement learning to drive the virtual arm in a 2D reaching task. Limb position was used to simultaneously control a robot arm using an improved network interface. Virtual arm muscle activations responded to motoneuron firing rates, with virtual arm muscles lengths encoded via population coding in the proprioceptive population. After training, the virtual arm performed reaching movements which were smoother and more realistic than those obtained using a simplistic arm model. This system provided access to both spiking network properties and to arm biophysical properties, including muscle forces. The use of a musculoskeletal virtual arm and the improved control system allowed the robot arm to perform movements which were smoother than those reported in our previous paper using a simplistic arm. This work provides a novel approach consisting of bidirectionally connecting a cortical model to a realistic virtual arm, and using the system output to drive a robotic arm in real time. Our techniques are applicable to the future development of brain neuroprosthetic control systems, and may enable enhanced brain-machine interfaces with the possibility for finer control of

  9. Cortical Spiking Network Interfaced with Virtual Musculoskeletal Arm and Robotic Arm.

    PubMed

    Dura-Bernal, Salvador; Zhou, Xianlian; Neymotin, Samuel A; Przekwas, Andrzej; Francis, Joseph T; Lytton, William W

    2015-01-01

    Embedding computational models in the physical world is a critical step towards constraining their behavior and building practical applications. Here we aim to drive a realistic musculoskeletal arm model using a biomimetic cortical spiking model, and make a robot arm reproduce the same trajectories in real time. Our cortical model consisted of a 3-layered cortex, composed of several hundred spiking model-neurons, which display physiologically realistic dynamics. We interconnected the cortical model to a two-joint musculoskeletal model of a human arm, with realistic anatomical and biomechanical properties. The virtual arm received muscle excitations from the neuronal model, and fed back proprioceptive information, forming a closed-loop system. The cortical model was trained using spike timing-dependent reinforcement learning to drive the virtual arm in a 2D reaching task. Limb position was used to simultaneously control a robot arm using an improved network interface. Virtual arm muscle activations responded to motoneuron firing rates, with virtual arm muscles lengths encoded via population coding in the proprioceptive population. After training, the virtual arm performed reaching movements which were smoother and more realistic than those obtained using a simplistic arm model. This system provided access to both spiking network properties and to arm biophysical properties, including muscle forces. The use of a musculoskeletal virtual arm and the improved control system allowed the robot arm to perform movements which were smoother than those reported in our previous paper using a simplistic arm. This work provides a novel approach consisting of bidirectionally connecting a cortical model to a realistic virtual arm, and using the system output to drive a robotic arm in real time. Our techniques are applicable to the future development of brain neuroprosthetic control systems, and may enable enhanced brain-machine interfaces with the possibility for finer control of

  10. Proprioceptive illusions created by vibration of one arm are altered by vibrating the other arm.

    PubMed

    Hakuta, Naoyuki; Izumizaki, Masahiko; Kigawa, Kazuyoshi; Murai, Norimitsu; Atsumi, Takashi; Homma, Ikuo

    2014-07-01

    There is some evidence that signals coming from both arms are used to determine the perceived position and movement of one arm. We examined whether the sense of position and movement of one (reference) arm is altered by increases in muscle spindle signals in the other (indicator) arm in blindfolded participants (n = 26). To increase muscle spindle discharge, we applied 70-80 Hz muscle vibration to the elbow flexors of the indicator arm. In a first experiment, proprioceptive illusions in the vibrated reference arm in a forearm position-matching task were compared between conditions in which the indicator arm elbow flexors were vibrated or not vibrated. We found that the vibration illusion of arm extension induced by vibration of reference arm elbow flexors was reduced in the presence of vibration of the indicator elbow flexors. In a second experiment, participants were asked to describe their perception of the illusion of forearm extension movements of the reference arm evoked by vibration of reference arm elbow flexors in response to on/off and off/on transitions of vibration of non-reference arm elbow flexors. When vibration of non-reference arm elbow flexors was turned on, they reported a sensation of slowing down of the illusion of the reference arm. When it was turned off, they reported a sensation of speeding up. To conclude, the present study shows that both the sense of limb position and the sense of limb movement of one arm are dependent to some extent on spindle signals coming from the other arm.

  11. Opportunity's Arm in 'Hover-Stow' Position

    NASA Technical Reports Server (NTRS)

    2006-01-01

    In January 2006, NASA's Mars Exploration Rover team adopted a new strategy for carrying Opportunity's robotic arm (the instrument deployment device with its turret of four tools at the end) when the rover is driving.

    On short drives over smooth terrain, Opportunity now holds the arm in a 'hover-stow' position as shown in this image taken by the navigation camera during the rover's 706th Martian day, or sol (Jan. 18, 2006), with elbow forward and the tool turret held above the rover deck. (In this image, the Moessbauer spectrometer is facing upwards, the alpha particle X-ray spectrometer faces to the right and the rock abrasion tool faces to the left). On longer or rougher drives, Opportunity still holds the arm in the original stow position used throughout the mission, tucked underneath the deck.

    During Opportunity's 654th sol (Nov. 25, 2005), symptoms began appearing that have been diagnosed as a broken wire in the motor windings for the azimuth actuator at the shoulder joint, a motor that moves the arm from side to side. The motor still works when given extra current, but the change in strategy for stowing the arm results from concern that, if the motor were to completely fail with the arm in the original stow position, the arm could no longer be unstowed for use. If that motor were to fail while the arm is in the hover-stow position, the arm could still be manipulated for full use of the tools on the turret. However, the hover-stow position gives less protection to the arm during drives. Concern about protecting the arm during drives led to the compromise strategy of using hover-stow only during short, smooth drives.

  12. Summary of compliant and multi-arm control at NASA. Langley Research Center

    NASA Technical Reports Server (NTRS)

    Harrison, Fenton W.

    1992-01-01

    The topics are presented in viewgraph form and include the: single arm system, single arm axis system, single arm control systems, single arm hand controller axis system, single arm position axis system, single arm vision axis system, single arm force axis system, multi-arm system, multi-arm axis system, and the dual arm hand control axis system with control signals.

  13. Sleep and eyewitness memory: Fewer false identifications after sleep when the target is absent from the lineup.

    PubMed

    Stepan, Michelle E; Dehnke, Taylor M; Fenn, Kimberly M

    2017-01-01

    Inaccurate eyewitness identifications are the leading cause of known false convictions in the United States. Moreover, improving eyewitness memory is difficult and often unsuccessful. Sleep consistently strengthens and protects memory from interference, particularly when a recall test is used. However, the effect of sleep on recognition memory is more equivocal. Eyewitness identification tests are often recognition based, thus leaving open the question of how sleep affects recognition performance in an eyewitness context. In the current study, we investigated the effect of sleep on eyewitness memory. Participants watched a video of a mock-crime and attempted to identify the perpetrator from a simultaneous lineup after a 12-hour retention interval that either spanned a waking day or night of sleep. In Experiment 1, we used a target-present lineup and, in Experiment 2, we used a target-absent lineup in order to investigate correct and false identifications, respectively. Sleep reduced false identifications in the target-absent lineup (Experiment 2) but had no effect on correct identifications in the target-present lineup (Experiment 1). These results are discussed with respect to memory strength and decision making strategies.

  14. Sleep and eyewitness memory: Fewer false identifications after sleep when the target is absent from the lineup

    PubMed Central

    Dehnke, Taylor M.; Fenn, Kimberly M.

    2017-01-01

    Inaccurate eyewitness identifications are the leading cause of known false convictions in the United States. Moreover, improving eyewitness memory is difficult and often unsuccessful. Sleep consistently strengthens and protects memory from interference, particularly when a recall test is used. However, the effect of sleep on recognition memory is more equivocal. Eyewitness identification tests are often recognition based, thus leaving open the question of how sleep affects recognition performance in an eyewitness context. In the current study, we investigated the effect of sleep on eyewitness memory. Participants watched a video of a mock-crime and attempted to identify the perpetrator from a simultaneous lineup after a 12-hour retention interval that either spanned a waking day or night of sleep. In Experiment 1, we used a target-present lineup and, in Experiment 2, we used a target-absent lineup in order to investigate correct and false identifications, respectively. Sleep reduced false identifications in the target-absent lineup (Experiment 2) but had no effect on correct identifications in the target-present lineup (Experiment 1). These results are discussed with respect to memory strength and decision making strategies. PMID:28877169

  15. Sensory-Feedback Exoskeletal Arm Controller

    NASA Technical Reports Server (NTRS)

    An, Bin; Massie, Thomas H.; Vayner, Vladimir

    2004-01-01

    An electromechanical exoskeletal arm apparatus has been designed for use in controlling a remote robotic manipulator arm. The apparatus, called a force-feedback exoskeleton arm master (F-EAM) is comfortable to wear and easy to don and doff. It provides control signals from the wearer s arm to a robot arm or a computer simulator (e.g., a virtual-reality system); it also provides force and torque feedback from sensors on the robot arm or from the computer simulator to the wearer s arm. The F-EAM enables the wearer to make the robot arm gently touch objects and finely manipulate them without exerting excessive forces. The F-EAM features a lightweight design in which the motors and gear heads that generate force and torque feedback are made smaller than they ordinarily would be: this is achieved by driving the motors to power levels greater than would ordinarily be used in order to obtain higher torques, and by providing active liquid cooling of the motors to prevent overheating at the high drive levels. The F-EAM (see figure) includes an assembly that resembles a backpack and is worn like a backpack, plus an exoskeletal arm mechanism. The FEAM has five degrees of freedom (DOFs) that correspond to those of the human arm: 1. The first DOF is that of the side-to-side rotation of the upper arm about the shoulder (rotation about axis 1). The reflected torque for this DOF is provided by motor 1 via drum 1 and a planar four-bar linkage. 2. The second DOF is that of the up-and-down rotation of the arm about the shoulder. The reflected torque for this DOF is provided by motor 2 via drum 2. 3. The third DOF is that of twisting of the upper arm about its longitudinal axis. This DOF is implemented in a cable remote-center mechanism (CRCM). The reflected torque for this DOF is provided by motor 3, which drives the upper-arm cuff and the mechanism below it. A bladder inflatable by gas or liquid is placed between the cuff and the wearer s upper arm to compensate for misalignment

  16. Small Arms Marksmanship Manual, NAVPERS 93863.

    ERIC Educational Resources Information Center

    Bureau of Naval Personnel, Washington, DC.

    The Navy's small arms marksmanship training program is designed to achieve proficiency for Navy personnel in handling the rifle, pistol andshotgun. The minimum objective of this program is to qualify Navy personnel as "Marksman," and ensure that personnel who are issued small arms for security, recreation, or competitions are fully qualified in…

  17. 76 FR 30497 - Armed Forces Day, 2011

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-25

    ... Forces Day, 2011 By the President of the United States of America A Proclamation The Armed Forces of the... its people. From our earliest days as a fledgling republic, the United States has relied on the.... On Armed Forces Day, let us salute the Soldiers, Sailors, Airmen, Marines, and Coast Guardsmen who...

  18. 78 FR 30731 - Armed Forces Day, 2013

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-22

    ... Forces Day, 2013 By the President of the United States of America A Proclamation Since the earliest days... Armed Forces Day, we honor those who serve bravely and sacrifice selflessly in our name. Our Soldiers... Saturday of each May as Armed Forces Day. I direct the Secretary of Defense on behalf of the Army, Navy...

  19. Design of a biomimetic robotic octopus arm.

    PubMed

    Laschi, C; Mazzolai, B; Mattoli, V; Cianchetti, M; Dario, P

    2009-03-01

    This paper reports the rationale and design of a robotic arm, as inspired by an octopus arm. The octopus arm shows peculiar features, such as the ability to bend in all directions, to produce fast elongations, and to vary its stiffness. The octopus achieves these unique motor skills, thanks to its peculiar muscular structure, named muscular hydrostat. Different muscles arranged on orthogonal planes generate an antagonistic action on each other in the muscular hydrostat, which does not change its volume during muscle contractions, and allow bending and elongation of the arm and stiffness variation. By drawing inspiration from natural skills of octopus, and by analysing the geometry and mechanics of the muscular structure of its arm, we propose the design of a robot arm consisting of an artificial muscular hydrostat structure, which is completely soft and compliant, but also able to stiffen. In this paper, we discuss the design criteria of the robotic arm and how this design and the special arrangement of its muscular structure may bring the building of a robotic arm into being, by showing the results obtained by mathematical models and prototypical mock-ups.

  20. 33 CFR 154.510 - Loading arms.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Loading arms. 154.510 Section 154.510 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION FACILITIES TRANSFERRING OIL OR HAZARDOUS MATERIAL IN BULK Equipment Requirements § 154.510 Loading arms. (a...

  1. 33 CFR 154.510 - Loading arms.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Loading arms. 154.510 Section 154.510 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION FACILITIES TRANSFERRING OIL OR HAZARDOUS MATERIAL IN BULK Equipment Requirements § 154.510 Loading arms. (a...

  2. Dual-arm manipulators with adaptive control

    NASA Technical Reports Server (NTRS)

    Seraji, Homayoun (Inventor)

    1991-01-01

    The described and improved multi-arm invention of this application presents three strategies for adaptive control of cooperative multi-arm robots which coordinate control over a common load. In the position-position control strategy, the adaptive controllers ensure that the end-effector positions of both arms track desired trajectories in Cartesian space despite unknown time-varying interaction forces exerted through a load. In the position-hybrid control strategy, the adaptive controller of one arm controls end-effector motions in the free directions and applied forces in the constraint directions; while the adaptive controller of the other arm ensures that the end-effector tracks desired position trajectories. In the hybrid-hybrid control strategy, the adaptive controllers ensure that both end-effectors track reference position trajectories while simultaneously applying desired forces on the load. In all three control strategies, the cross-coupling effects between the arms are treated as disturbances which are compensated for by the adaptive controllers while following desired commands in a common frame of reference. The adaptive controllers do not require the complex mathematical model of the arm dynamics or any knowledge of the arm dynamic parameters or the load parameters such as mass and stiffness. Circuits in the adaptive feedback and feedforward controllers are varied by novel adaptation laws.

  3. 49 CFR 236.702 - Arm, semaphore.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Arm, semaphore. 236.702 Section 236.702 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.702 Arm...

  4. Effort, success, and nonuse determine arm choice

    PubMed Central

    Xiao, Yupeng; Kim, Sujin; Yoshioka, Toshinori; Gordon, James; Osu, Rieko

    2015-01-01

    How do humans choose one arm or the other to reach single targets in front of the body? Current theories of reward-driven decisionmaking predict that choice results from a comparison of “action values,” which are the expected rewards for possible actions in a given state. In addition, current theories of motor control predict that in planning arm movements, humans minimize an expected motor cost that balances motor effort and endpoint accuracy. Here, we test the hypotheses that arm choice is determined by comparison of action values comprising expected effort and expected task success for each arm, as well as a handedness bias. Right-handed subjects, in either a large or small target condition, were first instructed to use each hand in turn to shoot through an array of targets and then to choose either hand to shoot through the same targets. Effort was estimated via inverse kinematics and dynamics. A mixed-effects logistic-regression analysis showed that, as predicted, both expected effort and expected success predicted choice, as did arm use in the preceding trial. Finally, individual parameter estimation showed that the handedness bias correlated with mean difference between right- and left-arm success, leading to overall lower use of the left arm. We discuss our results in light of arm nonuse in individuals' poststroke. PMID:25948869

  5. 49 CFR 236.702 - Arm, semaphore.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Arm, semaphore. 236.702 Section 236.702 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.702 Arm...

  6. 49 CFR 236.702 - Arm, semaphore.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Arm, semaphore. 236.702 Section 236.702 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.702 Arm...

  7. 49 CFR 236.702 - Arm, semaphore.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Arm, semaphore. 236.702 Section 236.702 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.702 Arm...

  8. [Aerodynamic characteristics of crewman's arms during windblast].

    PubMed

    Zhang, Yun-ran; Wu, Gui-rong

    2003-10-01

    To study the aerodynamic characteristics of crewman's arms with or without protective devices in the status with raised legs or not. The experiments were performed in an FL-24 transonic and supersonic wind tunnel, over Mach number range of 0.4-2.0, with 5 degrees-30 degrees angles of attack, 0 degrees - 90 degrees sideslip angles and Re number of (0.93-3.1) x 10(6). The test model was a 1/5-scale crewman/ejection seat combination. The aerodynamic characteristics of the various sections of crewman's arms were studied and analyzed. The results showed that 1) The effect of raised leg on the aerodynamic characteristics of the crewman's arms was very evident, and was related to the status of leg raising; 2) The sideslip considerably increased aerodynamic loads on the crewman's arms, in particular when beta=50 degrees the loads was severe in the test; 3) The tested protective devices was valid, the effectiveness of wind deflector in protecting crewman's arms was evident; 4) A formula for calculating aerodynamic force acting on crewman's arms was presented. 1)The tested protective devices was valid, and the effectiveness of wind deflector in protecting crewman's arms was evident; 2) An aerodynamic basis for the development of crewman windblast protective device was presented; 3)The calculation formula presented is useful in estimating aerodynamic forces of crewman's arms.

  9. 21 CFR 890.3640 - Arm sling.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Arm sling. 890.3640 Section 890.3640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3640 Arm sling. (a) Identification. An...

  10. 21 CFR 890.3640 - Arm sling.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Arm sling. 890.3640 Section 890.3640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3640 Arm sling. (a) Identification. An...

  11. 21 CFR 890.3640 - Arm sling.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Arm sling. 890.3640 Section 890.3640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3640 Arm sling. (a) Identification. An...

  12. 21 CFR 890.3640 - Arm sling.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Arm sling. 890.3640 Section 890.3640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3640 Arm sling. (a) Identification. An...

  13. 21 CFR 890.3640 - Arm sling.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Arm sling. 890.3640 Section 890.3640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3640 Arm sling. (a) Identification. An...

  14. Modulation of corticospinal input to the legs by arm and leg cycling in people with incomplete spinal cord injury.

    PubMed

    Zhou, R; Alvarado, L; Kim, S; Chong, S L; Mushahwar, V K

    2017-10-01

    The spinal cervico-lumbar interaction during rhythmic movements in humans has recently been studied; however, the role of arm movements in modulating the corticospinal drive to the legs is not well understood. The goals of this study were to investigate the effect of active rhythmic arm movements on the corticospinal drive to the legs ( study 1 ) and assess the effect of simultaneous arm and leg training on the corticospinal pathway after incomplete spinal cord injury (iSCI) ( study 2). In study 1 , neurologically intact (NI) participants or participants with iSCI performed combinations of stationary and rhythmic cycling of the arms and legs while motor evoked potentials (MEPs) were recorded from the vastus lateralis (VL) muscle. In the NI group, arm cycling alone could facilitate the VL MEP amplitude, suggesting that dynamic arm movements strongly modulate the corticospinal pathway to the legs. No significant difference in VL MEP between conditions was found in participants with iSCI. In study 2 , participants with iSCI underwent 12 wk of electrical stimulation-assisted cycling training: one group performed simultaneous arm and leg (A&L) cycling and the other legs-only cycling. MEPs in the tibialis anterior (TA) muscle were compared before and after training. After training, only the A&L group had a significantly larger TA MEP, suggesting increased excitability in the corticospinal pathway. The findings demonstrate the importance of arm movements in modulating the corticospinal drive to the legs and suggest that active engagement of the arms in lower limb rehabilitation may produce better neural regulation and restoration of function. NEW & NOTEWORTHY This study aimed to demonstrate the importance of arm movements in modulating the corticospinal drive to the legs. It provides direct evidence in humans that active movement of the arms could facilitate corticospinal transmission to the legs and, for the first time, shows that facilitation is absent after spinal cord

  15. Absent pulmonary valve

    MedlinePlus

    ... Kliegman RM, Stanton BF, St. Geme JW, Schor NF, eds. Nelson Textbook of Pediatrics . 20th ed. Philadelphia, ... Kliegman RM, Stanton BF, St. Geme JW, Schor NF, eds. Nelson Textbook of Pediatrics . 20th ed. Philadelphia, ...

  16. Absent menstrual periods - primary

    MedlinePlus

    ... Either of these problems may be due to: Anorexia (loss of appetite) Chronic or long-term illnesses, ... to begin. If the cause is the bulimia , anorexia or too much exercise, periods will often begin ...

  17. Absent menstrual periods - secondary

    MedlinePlus

    ... example, from strict or extreme diets or after gastric bypass surgery ) Other causes include: Brain (pituitary) tumors Drugs for cancer treatment Drugs to treat schizophrenia or psychosis Overactive ...

  18. 31 CFR 543.301 - Arms or any related materiel.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Arms or any related materiel. 543.301... Definitions § 543.301 Arms or any related materiel. The term arms or any related materiel means arms or... of arms and related materiel and technical training and assistance intended solely for support of or...

  19. 31 CFR 543.301 - Arms or any related materiel.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Arms or any related materiel. 543.301... Definitions § 543.301 Arms or any related materiel. The term arms or any related materiel means arms or... of arms and related materiel and technical training and assistance intended solely for support of or...

  20. 31 CFR 543.301 - Arms or any related materiel.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Arms or any related materiel. 543.301... Definitions § 543.301 Arms or any related materiel. The term arms or any related materiel means arms or... of arms and related materiel and technical training and assistance intended solely for support of or...

  1. 31 CFR 543.301 - Arms or any related materiel.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Arms or any related materiel. 543.301... Definitions § 543.301 Arms or any related materiel. The term arms or any related materiel means arms or... of arms and related materiel and technical training and assistance intended solely for support of or...

  2. Holographic gunsights for small arms

    NASA Astrophysics Data System (ADS)

    Tai, Anthony M.; Sieczka, Eric J.; Radler, Richard; Upatnieks, Juris

    1996-05-01

    Holographic gunsights were first demonstrated in the mid 1970s by researchers at the Environmental Research Institute of Michigan (ERIM) under contracts with the Air Force and the Army. The sights utilized He-Ne gas lasers and were designed for use with large weapons systems. With the advent of low cost visible laser diode, ERIM formed a new company, EOTech, to develop, manufacture and market a holographic gun sight for small arms. A hologram is used to reconstruct the image of a reticle pattern that appears at the target plane. Unlike red-dot sights, virtually any reticle pattern, 2D or 3D, can be formed. The design challenges include an opto-mechanical package that is compact, light weight and low cost which can withstand recoils up to 4,000 Gs and provide fine elevation/windage pointing adjustments, and optics that are aberration-free and stable over a wide temperature range. Manufacturing challenges include the mass production of high quality holographic optics at low cost and the precision alignment of the very low f/number optics.

  3. Robotic Arm Comprising Two Bending Segments

    NASA Technical Reports Server (NTRS)

    Mehling, Joshua S.; Difler, Myron A.; Ambrose, Robert O.; Chu, Mars W.; Valvo, Michael C.

    2010-01-01

    The figure shows several aspects of an experimental robotic manipulator that includes a housing from which protrudes a tendril- or tentacle-like arm 1 cm thick and 1 m long. The arm consists of two collinear segments, each of which can be bent independently of the other, and the two segments can be bent simultaneously in different planes. The arm can be retracted to a minimum length or extended by any desired amount up to its full length. The arm can also be made to rotate about its own longitudinal axis. Some prior experimental robotic manipulators include single-segment bendable arms. Those arms are thicker and shorter than the present one. The present robotic manipulator serves as a prototype of future manipulators that, by virtue of the slenderness and multiple- bending capability of their arms, are expected to have sufficient dexterity for operation within spaces that would otherwise be inaccessible. Such manipulators could be especially well suited as means of minimally invasive inspection during construction and maintenance activities. Each of the two collinear bending arm segments is further subdivided into a series of collinear extension- and compression-type helical springs joined by threaded links. The extension springs occupy the majority of the length of the arm and engage passively in bending. The compression springs are used for actively controlled bending. Bending is effected by means of pairs of antagonistic tendons in the form of spectra gel spun polymer lines that are attached at specific threaded links and run the entire length of the arm inside the spring helix from the attachment links to motor-driven pulleys inside the housing. Two pairs of tendons, mounted in orthogonal planes that intersect along the longitudinal axis, are used to effect bending of each segment. The tendons for actuating the distal bending segment are in planes offset by an angle of 45 from those of the proximal bending segment: This configuration makes it possible to

  4. Characterization of the first intragenic SATB2 duplication in a girl with intellectual disability, nearly absent speech and suspected hypodontia.

    PubMed

    Kaiser, Ann-Sophie; Maas, Bianca; Wolff, Anna; Sutter, Christian; Janssen, Johannes W G; Hinderhofer, Katrin; Moog, Ute

    2015-05-01

    SATB2, a gene encoding a highly conserved DNA-binding protein, is known to have an important role in craniofacial and neuronal development. Only a few patients with SATB2 variants have been described so far. Recently, Döcker et al provided a summary of these patients and delineated the SAS (SATB2-associated syndrome). We here report on a girl with intellectual disability, nearly absent speech and suspected hypodontia who was shown to carry an intragenic SATB2 tandem duplication hypothesized to lead to haploinsufficiency of SATB2. Preliminary information on this patient had already been included in the article by Döcker et al. We want to give a detailed description of the patient's phenotype and genotype, providing further insight into the spectrum of the molecular mechanisms leading to SAS.

  5. Adaptive control of dual-arm robots

    NASA Technical Reports Server (NTRS)

    Seraji, H.

    1987-01-01

    Three strategies for adaptive control of cooperative dual-arm robots are described. In the position-position control strategy, the adaptive controllers ensure that the end-effector positions of both arms track desired trajectories in Cartesian space despite unknown time-varying interaction forces exerted through the load. In the position-hybrid control strategy, the adaptive controller of one arm controls end-effector motions in the free directions and applied forces in the constraint directions, while the adaptive controller of the other arm ensures that the end-effector tracks desired position trajectories. In the hybrid-hybrid control strategy, the adaptive controllers ensure that both end-effectors track reference position trajectories while simultaneously applying desired forces on the load. In all three control strategies, the cross-coupling effects between the arms are treated as disturbances which are rejected by the adaptive controllers while following desired commands in a common frame of reference. The adaptive controllers do not require the complex mathematical model of the arm dynamics or any knowledge of the arm dynamic parameters or the load parameters such as mass and stiffness. The controllers have simple structures and are computationally fast for on-line implementation with high sampling rates.

  6. The evolution of neuroArm.

    PubMed

    Sutherland, Garnette R; Wolfsberger, Stefan; Lama, Sanju; Zarei-nia, Kourosh

    2013-01-01

    Intraoperative imaging disrupts the rhythm of surgery despite providing an excellent opportunity for surgical monitoring and assessment. To allow surgery within real-time images, neuroArm, a teleoperated surgical robotic system, was conceptualized. The objective was to design and manufacture a magnetic resonance-compatible robot with a human-machine interface that could reproduce some of the sight, sound, and touch of surgery at a remote workstation. University of Calgary researchers worked with MacDonald, Dettwiler and Associates engineers to produce a requirements document, preliminary design review, and critical design review, followed by the manufacture, preclinical testing, and clinical integration of neuroArm. During the preliminary design review, the scope of the neuroArm project changed to performing microsurgery outside the magnet and stereotaxy inside the bore. neuroArm was successfully manufactured and installed in an intraoperative magnetic resonance imaging operating room. neuroArm was clinically integrated into 35 cases in a graded fashion. As a result of this experience, neuroArm II is in development, and advances in technology will allow microsurgery within the bore of the magnet. neuroArm represents a successful interdisciplinary collaboration. It has positive implications for the future of robotic technology in neurosurgery in that the precision and accuracy of robots will continue to augment human capability.

  7. Science, Technology and the Nuclear Arms Race

    NASA Astrophysics Data System (ADS)

    Schroeer, Dietrich

    1984-09-01

    A comprehensive survey of the nuclear arms race from a technological point of view, which will appeal to the scientist and non-scientist alike. Provides information for the layman on this current topic and is designed for undergraduate courses in political science, history, international studies, as well as physics courses on the subject. Explores the motivation behind the development of various nuclear arms technologies and their deployment and examines the effects these technologies have on military, political and social strategies. Discusses the nature of deterrence and alternatives to it, arms control, and disarmament.

  8. Sprinkle Test by Phoenix Robotic Arm Movie

    NASA Image and Video Library

    2008-06-10

    NASA Phoenix Mars Lander used its Robotic Arm during the mission 15th Martian day since landing June 9, 2008 to test a prinkle method for delivering small samples of soil to instruments on the lander deck.

  9. Self-locking telescoping manipulator arm

    NASA Technical Reports Server (NTRS)

    Nesmith, M. F. (Inventor)

    1985-01-01

    A telescoping manipulator arm and pivotable finger assembly are disclosed. The telescoping arm assembly includes a generally T-shaped arm having three outwardly extending fingers guided on grooved roller guides to compensate for environmental variations. The pivotable finger assembly includes four pivoting fingers. Arcuate teeth are formed on the ends of the fingers. A rack having teeth on four sides meshes with each one of the fingers. One surface of the rack includes teeth along its entire surface which mesh with teeth of one of the fingers. The teeth at the remote end of the rack engage teeth of a gear wheel. The wheel includes a worm which meshes with a worn drive shaft of the drive motor providing a ninety degree self-locking drive for locking the fingers in a desired position. A similar drive provides a self-locking drive for positioning the telescoping arm.

  10. Working End of Robotic Arm on Phoenix

    NASA Image and Video Library

    2007-08-02

    This illustration shows some of the components on and near the end of the robotic arm on NASA Phoenix Mars Lander. Primary and secondary blades on the scoop that aided in the collection of soil samples.

  11. Rasp Tool on Phoenix Robotic Arm Model

    NASA Image and Video Library

    2008-07-15

    This close-up photograph taken at the Payload Interoperability Testbed at the University of Arizona, Tucson, shows the motorized rasp protruding from the bottom of the scoop on the engineering model of NASA Phoenix Mars Lander Robotic Arm.

  12. Opportunity Arm and Gagarin Rock, Sol 405

    NASA Image and Video Library

    2011-04-08

    NASA Mars Exploration Rover Opportunity used its rock abrasion tool on a rock informally named Gagarin, leaving a circular mark. At the end of the rover arm, the tool turret is positioned with the rock abrasion tool pointing upward.

  13. Radiation Pattern of Chair Armed Microstrip Antenna

    NASA Astrophysics Data System (ADS)

    Mishra, Rabindra Kishore; Sahu, Kumar Satyabrat

    2016-12-01

    This work analyzes planar antenna conformable to chair arm shaped surfaces for WLAN application. Closed form expressions for its radiation pattern are developed and validated using measurements on prototype and commercial EM code at 2.4 GHz.

  14. End effector on orbiter's RMS arm

    NASA Image and Video Library

    2001-03-13

    STS102-E-5201 (13 March 2001) --- A view of the interior of the end effector apparatus on the end of the Canadian-built remote manipulator system (RMS) arm. The photograph was taken with a digital still camera.

  15. The molecular spiral arms of NGC 6946

    NASA Technical Reports Server (NTRS)

    Tacconi, L. J.; Xie, S.

    1990-01-01

    From CO-12(J=1 to 0) observations at 45 seconds resolution Tacconi and Young (1989) have found evidence for enhancements in both the CO emissivity and the massive star formation efficiency (MSFE) on optical spiral arms of the bright spiral galaxy NGC 6946. In the optically luminous and well-defined spiral arm in the NE quadrant, there are enhancements in both the H2 surface density and MSFE relative to the interarm regions. In contrast, a poorly defined arm in the SW shows no arm-interarm contrast in the MSFE. To further investigate the molecular gas content of these two spiral arms, researchers have made CO-12 J=2 to 1 and 3 to 2 observations with the James Clerk Maxwell Telescope. In the J=2 to 1 line, they made observations of the NE and SW spiral arm and interarm regions in 4 x 9 10 seconds spaced grids (36 points per grid). Because of decreased sensitivity in the J=3 to 2 line, they were limited to mapping the two arm regions in 2 x 3 10 seconds spaced grids (6 points per grid). The centers of each of the grids lie 2.4 minutes to the NE and 2.3 minutes to the SW of the nucleus of NGC 6946. With the CO J=2 to 1 data researchers are able to fully resolve the two observed spiral arms in NGC 6946. In both cases the CO emission is largely confined to the optical spiral arm regions with the peak observed T asterisk sub A being up to 4 times higher on the spiral arms than in the interarm regions. Researchers are currently estimating massive star formation efficiencies on and off the spiral arms through direct comparison of the CO maps with an H alpha image. They are also comparing the CO J=2 to 1 data with an HI map made at similar resolution. Thus, they will be able to determine structure in all components of the IS on scales of less than 20 inches.

  16. Student measurement of blood pressure using a simulator arm compared with a live subject's arm.

    PubMed

    Lee, Jennifer J; Sobieraj, Diana M; Kuti, Effie L

    2010-06-15

    To compare accuracy of blood pressure measurements using a live subject and a simulator arm, and to determine students' preferences regarding measurement. This was a crossover study comparing blood pressure measurements from a live subject and a simulator arm. Students completed an anonymous survey instrument defining opinions on ease of measurement. Fifty-seven students completed blood pressure measurements on live subjects while 72 students completed blood pressure measurements using the simulator arm. There were no significant systematic differences between the 2 measurement techniques. Systolic blood pressure measurements from a live subject arm were less likely to be within 4 mm Hg compared with measurements of a simulator arm. Diastolic blood pressure measurements were not significantly different between the 2 techniques. Accuracy of student measurement of blood pressure using a simulator arm was similar to the accuracy with a live subject. There was no difference in students' preferences regarding measurement techniques.

  17. Modal kinematics for multisection continuum arms.

    PubMed

    Godage, Isuru S; Medrano-Cerda, Gustavo A; Branson, David T; Guglielmino, Emanuele; Caldwell, Darwin G

    2015-05-13

    This paper presents a novel spatial kinematic model for multisection continuum arms based on mode shape functions (MSF). Modal methods have been used in many disciplines from finite element methods to structural analysis to approximate complex and nonlinear parametric variations with simple mathematical functions. Given certain constraints and required accuracy, this helps to simplify complex phenomena with numerically efficient implementations leading to fast computations. A successful application of the modal approximation techniques to develop a new modal kinematic model for general variable length multisection continuum arms is discussed. The proposed method solves the limitations associated with previous models and introduces a new approach for readily deriving exact, singularity-free and unique MSF's that simplifies the approach and avoids mode switching. The model is able to simulate spatial bending as well as straight arm motions (i.e., pure elongation/contraction), and introduces inverse position and orientation kinematics for multisection continuum arms. A kinematic decoupling feature, splitting position and orientation inverse kinematics is introduced. This type of decoupling has not been presented for these types of robotic arms before. The model also carefully accounts for physical constraints in the joint space to provide enhanced insight into practical mechanics and impose actuator mechanical limitations onto the kinematics thus generating fully realizable results. The proposed method is easily applicable to a broad spectrum of continuum arm designs.

  18. A chromogranin A ELISA absent of an apparent high-dose hook effect observed in other chromogranin A ELISAs.

    PubMed

    Erickson, J Alan; Grenache, David G

    2016-01-15

    Routine testing for chromogranin A (CgA) using an established commercial ELISA revealed an apparent high-dose hook effect in approximately 15% of specimens. Investigations found the same effect in two additional ELISAs. We hypothesized that a CgA derived peptide(s) at high concentrations was responsible but experiments were inconclusive. Here we describe the analytical performance characteristics of the Chromoa™ CgA ELISA that did not display the apparent high-dose hook effect. Performance characteristics of the Chromoa ELISA were assessed. The reference interval was established utilizing healthy volunteers. Specimens producing the apparent high-dose hook effect in other assays were evaluated using the Chromoa ELISA. The limit of detection was 8ng/ml. Linearity was acceptable (slope=1.04, intercept=18.1 and r(2)=0.997). CVs were ≤4.6 and ≤9.3% for repeatability and within-laboratory imprecision, respectively. CgA was stable at ambient and refrigerated temperatures for a minimum of two and 14days, respectively. An upper reference interval limit of 95ng/ml was established. Specimens demonstrating the apparent high-dose hook effect in other ELISAs did not exhibit the phenomenon using the Chromoa ELISA. The Chromoa ELISA demonstrates acceptable performance for quantifying serum CgA. The apparent high-dose hook effect exhibited in other ELISAs was absent using the Chromoa assay. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Bilateral Malar Reconstruction Using Patient-Specific Polyether Ether Ketone Implants in Treacher-Collins Syndrome Patients With Absent Zygomas.

    PubMed

    Sainsbury, David C G; George, Alan; Forrest, Christopher R; Phillips, John H

    2017-03-01

    The authors performed bilateral malar reconstruction using polyether ether ketone implants in 3 patients with Treacher-Collins syndrome with absent, as opposed to hypoplastic, zygomata. These patient-specific implants were fabricated using computed-aided design software reformatted from three-dimensional bony preoperative computed tomography images. The first time the authors performed this procedure the implant compressed the globe resulting in temporary anisocoria that was quickly recognized intraoperatively. The implant was immediately removed and the patient made a full-recovery with no ocular disturbance. The computer-aided design and manufacturing process was adjusted to include periorbital soft-tissue boundaries to aid in contouring the new implants. The same patient, and 2 further patients, subsequently underwent malar reconstruction using this soft tissue periorbital boundary fabrication process with an additional 2 mm relief removed from the implant's orbital surface. These subsequent procedures were performed without complication and with pleasing aesthetic results. The authors describe their experience and the salutary lessons learnt.

  20. Absent Inferior Vena Cava Leading to Recurrent Lower Extremity Deep Vein Thrombosis in a United States Marine.

    PubMed

    Kim, Sang; Kunkel, Scott; Browske, Kristin

    2018-01-01

    Anomalies of the inferior vena cava (AIVC) are rare but well-recognized anatomic abnormalities that can lead to clinically significant deep vein thrombosis (DVT) in a subset of otherwise healthy patients. This report illustrates an uncommon congenital anomaly that military clinicians should consider when evaluating unprovoked DVT in young patients. Single case report and literature review. We describe a case of a 24-yr-old United States Marine who presented with abdominal pain for 2 wk. After conservative therapy failed, a contrast-enhanced abdominal computed tomography (CT) scan was performed. The CT scan revealed an absent inferior vena cava with evidence of right venous thrombophlebitis. We include four contrast-enhanced helical CT scans that illustrate this phenomenon. Due to the lack of available studies and data, we do not know the relative risk of DVT in patients with AIVC. However, the literature review suggests that there is a pro-thrombogenic effect of this congenital anomaly. Clinicians should include AIVC in their differential when treating young, otherwise healthy patients with unprovoked DVT. This population is much more likely to have an AIVC than the general population. In addition to thrombophilia markers, a contrast-enhanced CT scan should be considered as part of the initial workup. Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  1. Retinal Expression of the Drosophila eyes absent Gene Is Controlled by Several Cooperatively Acting Cis-regulatory Elements

    PubMed Central

    Neuman, Sarah D.; Bashirullah, Arash; Kumar, Justin P.

    2016-01-01

    The eyes absent (eya) gene of the fruit fly, Drosophila melanogaster, is a member of an evolutionarily conserved gene regulatory network that controls eye formation in all seeing animals. The loss of eya leads to the complete elimination of the compound eye while forced expression of eya in non-retinal tissues is sufficient to induce ectopic eye formation. Within the developing retina eya is expressed in a dynamic pattern and is involved in tissue specification/determination, cell proliferation, apoptosis, and cell fate choice. In this report we explore the mechanisms by which eya expression is spatially and temporally governed in the developing eye. We demonstrate that multiple cis-regulatory elements function cooperatively to control eya transcription and that spacing between a pair of enhancer elements is important for maintaining correct gene expression. Lastly, we show that the loss of eya expression in sine oculis (so) mutants is the result of massive cell death and a progressive homeotic transformation of retinal progenitor cells into head epidermis. PMID:27930646

  2. 32 CFR 623.5 - Loan of arms and accouterments.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 3 2013-07-01 2013-07-01 false Loan of arms and accouterments. 623.5 Section... LOAN OF ARMY MATERIEL § 623.5 Loan of arms and accouterments. (a) General. (1) Loan of arms and... number visibility. Loans of arms and accouterments as included herein are not applicable to Army National...

  3. 31 CFR 546.301 - Arms or any related materiel.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Arms or any related materiel. 546.301 Section 546.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE... Definitions § 546.301 Arms or any related materiel. The term arms or any related materiel shall mean arms or...

  4. 49 CFR 234.255 - Gate arm and gate mechanism.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Gate arm and gate mechanism. 234.255 Section 234... Maintenance, Inspection, and Testing Inspections and Tests § 234.255 Gate arm and gate mechanism. (a) Each gate arm and gate mechanism shall be inspected at least once each month. (b) Gate arm movement shall be...

  5. 31 CFR 546.301 - Arms or any related materiel.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Arms or any related materiel. 546.301 Section 546.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE... Definitions § 546.301 Arms or any related materiel. The term arms or any related materiel shall mean arms or...

  6. 49 CFR 234.255 - Gate arm and gate mechanism.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Gate arm and gate mechanism. 234.255 Section 234... Maintenance, Inspection, and Testing Inspections and Tests § 234.255 Gate arm and gate mechanism. (a) Each gate arm and gate mechanism shall be inspected at least once each month. (b) Gate arm movement shall be...

  7. 31 CFR 546.301 - Arms or any related materiel.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Arms or any related materiel. 546.301 Section 546.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE... Definitions § 546.301 Arms or any related materiel. The term arms or any related materiel shall mean arms or...

  8. 31 CFR 546.301 - Arms or any related materiel.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Arms or any related materiel. 546.301 Section 546.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE... Definitions § 546.301 Arms or any related materiel. The term arms or any related materiel shall mean arms or...

  9. 49 CFR 234.255 - Gate arm and gate mechanism.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Gate arm and gate mechanism. 234.255 Section 234....255 Gate arm and gate mechanism. (a) Each gate arm and gate mechanism shall be inspected at least once each month. (b) Gate arm movement shall be observed for proper operation at least once each month. (c...

  10. 49 CFR 234.255 - Gate arm and gate mechanism.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Gate arm and gate mechanism. 234.255 Section 234....255 Gate arm and gate mechanism. (a) Each gate arm and gate mechanism shall be inspected at least once each month. (b) Gate arm movement shall be observed for proper operation at least once each month. (c...

  11. 32 CFR 623.5 - Loan of arms and accouterments.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 3 2014-07-01 2014-07-01 false Loan of arms and accouterments. 623.5 Section... LOAN OF ARMY MATERIEL § 623.5 Loan of arms and accouterments. (a) General. (1) Loan of arms and... number visibility. Loans of arms and accouterments as included herein are not applicable to Army National...

  12. 32 CFR 623.5 - Loan of arms and accouterments.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 3 2012-07-01 2009-07-01 true Loan of arms and accouterments. 623.5 Section 623... LOAN OF ARMY MATERIEL § 623.5 Loan of arms and accouterments. (a) General. (1) Loan of arms and... number visibility. Loans of arms and accouterments as included herein are not applicable to Army National...

  13. 49 CFR 234.255 - Gate arm and gate mechanism.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Gate arm and gate mechanism. 234.255 Section 234....255 Gate arm and gate mechanism. (a) Each gate arm and gate mechanism shall be inspected at least once each month. (b) Gate arm movement shall be observed for proper operation at least once each month. (c...

  14. ARM Airborne Carbon Measurements (ARM-ACME) and ARM-ACME 2.5 Final Campaign Reports

    SciTech Connect

    Biraud, S. C.; Tom, M. S.; Sweeney, C.

    2016-01-01

    We report on a 5-year multi-institution and multi-agency airborne study of atmospheric composition and carbon cycling at the Atmospheric Radiation Measurement (ARM) Climate Research Facility’s Southern Great Plains (SGP) site, with scientific objectives that are central to the carbon-cycle and radiative-forcing goals of the U.S. Global Change Research Program and the North American Carbon Program (NACP). The goal of these measurements is to improve understanding of 1) the carbon exchange of the Atmospheric Radiation Measurement (ARM) SGP region; 2) how CO 2 and associated water and energy fluxes influence radiative-forcing, convective processes, and CO 2 concentrations over the ARM SGPmore » region, and 3) how greenhouse gases are transported on continental scales.« less

  15. Molecular clouds in the Carina arm

    NASA Technical Reports Server (NTRS)

    Grabelsky, D. A.

    1986-01-01

    Results from the first large-scale survey in the CO(J = 1 to 0) line of the Vela-Carina-Centaurus region of the Southern Milky Way are reported. The observations, made with the Columbia University 1.2 m millimeter-wave telescope at Cerro Tololo, were spaced every beamwidth (0.125 deg) in the range 270 deg is less than or = l is less than or = 300 deg and -1 deg less than or = b less then or = 1 deg, with latitude extensions to cover all Carina arm emission beyond absolute b = 1 deg. In a concurrent survey made with the same telescope, every half-degree in latitude and longitude was sampled. Both surveys had a spectral coverage of 330 km/s with a resolution of 1.3 km/s. The Carina arm is the dominant feature in the data. Its abrupt tangent at l is approx. = 280 deg and characteristic loop in the l,v diagram are unmistakable evidence for CO spiral structure. When the emission is integrated over velocity and latitude, the height of the step seen in the tangent direction suggests that the arm-interarm contrast is at least 13:1. Comparison of the CO and H I data shows close agreement between these two species in a segment of the arm lying outside the solar circle. The distribution of the molecular layer about the galactic plane in the outer Galaxy is determined. Between R = 10.5 and 12.5 kpc, the average CO midplane dips from z = -48 to -167 pc below the b = 0 deg plane, following a similar well-known warping of the H I layer. In the same range of radii the half-thickness of the CO layer increases from 112 to 182 pc. Between l = 270 deg and 300 deg, 27 molecular clouds are identified and cataloged along with heliocentric distances and masses. An additional 16 clouds beyond 300 deg are cataloged from an adjoining CO survey made with the same telescope. The average mass for the Carina arm clouds is 1.4x 10(6)M (solar), and the average intercloud spacing along the arm is 700 pc. Comparison of the distribution of the Carina arm clouds with that of similarly massive

  16. Research on the measurement technology of effective arm length of swing arm profilometer

    NASA Astrophysics Data System (ADS)

    Chen, Lin; Jing, Hongwei; Wei, Zhongwei; Li, Jie; Cao, Xuedong

    2014-09-01

    When the swing arm profilometer(SAP) measuring the mirror, the effective arm length of SAP which haves an obvious influence on the measurement results of the mirror surface shape needs to be measured accurately. It requires the measurement uncertainty of the effective arm length to reach 10μm in order to meet the measurement requirements, in this paper, we present a kind of technology based on laser tracker to measure the effective arm length of SAP. When the swing arm rotates around the shaft axis of swing arm rotary stage, the probe and two laser tracker balls form three sections of circular arc around the shaft axis of swing arm rotary stage in space. Laser tracker tracks and measures the circular arcs of two laser tracker balls, the center coordinates of the circular plane of circular arc can be calculated by data processing. The linear equation that passes through the two center coordinates is the equation of the shaft axis of rotary stage, the vertical distance from the probe to the shaft axis of rotary stage which can be calculated refer to the equation from the point to the line is the effective arm length. After Matlab simulation, this measurement method can meet the measurement accuracy.

  17. Organization of octopus arm movements: a model system for studying the control of flexible arms.

    PubMed

    Gutfreund, Y; Flash, T; Yarom, Y; Fiorito, G; Segev, I; Hochner, B

    1996-11-15

    Octopus arm movements provide an extreme example of controlled movements of a flexible arm with virtually unlimited degrees of freedom. This study aims to identify general principles in the organization of these movements. Video records of the movements of Octopus vulgaris performing the task of reaching toward a target were studied. The octopus extends its arm toward the target by a wave-like propagation of a bend that travels from the base of the arm toward the tip. Similar bend propagation is seen in other octopus arm movements, such as locomotion and searching. The kinematics (position and velocity) of the midpoint of the bend in three-dimensional space were extracted using the direct linear transformation algorithm. This showed that the bend tends to move within a single linear plane in a simple, slightly curved path connecting the center of the animal's body with the target location. Approximately 70% of the reaching movements demonstrated a stereotyped tangential velocity profile. An invariant profile was observed when movements were normalized for velocity and distance. Two arms, extended together in the same behavioral context, demonstrated identical velocity profiles. The stereotyped features of the movements were also observed in spontaneous arm extensions (not toward an external target). The simple and stereotypic appearance of the bend trajectory suggests that the position of the bend in space and time is the controlled variable. We propose that this strategy reduces the immense redundancy of the octopus arm movements and hence simplifies motor control.

  18. Representation of virtual arm movements in precuneus.

    PubMed

    Dohle, Christian; Stephan, Klaus Martin; Valvoda, Jakob T; Hosseiny, Omid; Tellmann, Lutz; Kuhlen, Torsten; Seitz, Rüdiger J; Freund, Hans-Joachim

    2011-02-01

    Arm movements can easily be adapted to different biomechanical constraints. However, the cortical representation of the processing of visual input and its transformation into motor commands remains poorly understood. In a visuo-motor dissociation paradigm, subjects were presented with a 3-D computer-graphical representation of a human arm, presenting movements of the subjects' right arm either as right or left arm. In order to isolate possible effects of coordinate transformations, coordinate mirroring at the body midline was implemented independently. In each of the resulting four conditions, 10 normal, right-handed subjects performed three runs of circular movements, while being scanned with O(15)-Butanol-PET. Kinematic analysis included orientation and accuracy of a fitted ellipsoid trajectory. Imaging analysis was performed with SPM 99 with activations threshold at P < 0.0001 (not corrected). The shape of the trajectory was dependent on the laterality of the arm, irrespective of movement mirroring, and accompanied by a robust activation difference in the contralateral precuneus. Movement mirroring decreased movement accuracy, which was related to increased activation in the left insula. Those two movement conditions that cannot be observed in reality were related to an activation focus at the left middle temporal gyrus, but showed no influence on movement kinematics. These findings demonstrate the prominent role of the precuneus for mediating visuo-motor transformations and have implications for the use of mirror therapy and virtual reality techniques, especially avatars, such as Nintendo Wii in neurorehabilitation.

  19. Spiral Arm Morphology of Nearby Galaxies

    NASA Astrophysics Data System (ADS)

    Ann, Hong Bae; Lee, Hyun-Rok

    2013-06-01

    We analyze the spiral structure of 1725 nearby spiral galaxies with redshift less than 0.02. We use the color images provided by the Sloan Digital Sky Survey. We determine the arm classes (grand design, multiple-arm, flocculent) and the broad Hubble types (early, intermediate, late) as well as the bar types (SA, SAB, SB) by visual inspection. We find that flocculent galaxies are mostly of late Hubble type while multiple-arm galaxies are likely to be of early Hubble type. The fractional distribution of grand design galaxies is nearly constant along the Hubble type. The dependence of arm class on bar type is not as strong as that of the Hubble type. However, there is about a three times larger fraction of grand design spirals in SB galaxies than in SA galaxies, with nearly constant fractions of multiple-arm galaxies. However, if we consider the Hubble type and bar type together, grand design spirals are more frequent in early types than in late types for SA and SAB galaxies, while they are almost constant along the Hubble type for SB galaxies. There are clear correlations between spiral structures and the local background density: strongly barred, early-type, grand design spirals favor high-density regions, while non-barred, late-type, flocculent galaxies are likely to be found in low-density regions.

  20. Stellar complexes in spiral arms of galaxies

    NASA Astrophysics Data System (ADS)

    Efremov, Yu. N.

    The history of the introduction and development of the star complexes conception is briefly described. These large groups of stars were picked out and named as such ones in our Galaxy with argumentation and evidence for their physical unity (using the Cepheid variables the distances and ages of which are easy determined from their periods); anyway earlier the complexes were noted along the spiral arms of the Andromeda galaxy, but were not recognized as a new kind of star group. The chains of complexes along the spiral arms are observed quite rarely; their origin is explained by magneto- gravitational or purely gravitational instability developing along the arm. It is not clear why these chains are quite a rare phenomenon - and more so why sometimes the regular chain of complexes are observed in one arm only. Probably intergalactic magnetic field participated in formation of such chains. Apart from the complexes located along the arms, there are isolated giant complexes known (up to 700 pc in diameter) which look like super-gigantic but rather rarefied globular clusters. Until now only two of these formations are studied, in NGC 6946 and M51.

  1. The spiral arms of the Milky Way: The relative location of each different arm tracer within a typical spiral arm width

    SciTech Connect

    Vallée, Jacques P., E-mail: jacques.vallee@nrc-cnrc.gc.ca

    2014-07-01

    From the Sun's location in the Galactic disk, different arm tracers (CO, H I, hot dust, etc.) have been employed to locate a tangent to each spiral arm. Using all various and different observed spiral arm tracers (as published elsewhere), we embark on a new goal, namely the statistical analysis of these published data (data mining) to statistically compute the mean location of each spiral arm tracer. We show for a typical arm cross-cut, a separation of 400 pc between the mid-arm and the dust lane (at the inner edge of the arm, toward the Galactic center). Are some armsmore » major and others minor? Separating arms into two sets, as suggested by some, we find the same arm widths between the two sets. Our interpretation is that we live in a multiple (four-arm) spiral (logarithmic) pattern (around a pitch angle of 12°) for the stars and gas in the Milky Way, with a sizable interarm separation (around 3 kpc) at the Sun's location and the same arm width for each arm (near 400 pc from mid-arm to dust lane).« less

  2. Isolated effects of peripheral arm and central body cooling on arm performance.

    PubMed

    Giesbrecht, G G; Wu, M P; White, M D; Johnston, C E; Bristow, G K

    1995-10-01

    Whole body cooling impairs manual arm performance. The independent contributions of local (peripheral) and/or whole body (central) cooling are not known. Therefore, a protocol was developed in which the arm and the rest of the body could be independently cooled. Biceps temperature (Tmus), at a depth of 20 mm, and esophageal temperature (Tes) were measured. Six subjects were immersed to the clavicles in a tank (body tank) of water under 3 conditions: 1) cold body-cold arm (CB-CA); 2) warm body-cold arm (WB-CA); and 3) cold body-warm arm (CB-WA). In the latter two conditions, subjects placed their dominant arm in a separate (arm) tank. Water temperature (Tw) in each tank was independently controlled. In conditions requiring cold body and/or cold arm, Tw in the appropriate tanks was 8 degrees C. In conditions requiring warm body and/or warm arm, Tw in the appropriate tanks was adjusted between 29 and 38 degrees C to maintain body/arm temperature at baseline values. A battery of 6 tests, requiring fine or gross motor movements, were performed immediately before immersion and after 15, 45, and 70 minutes of immersion. In CB-CA, Tes decreased from an average of 37.2 to 35.6 degrees C and Tmus decreased from 34.6 to 22.0 degrees C. In WB-CA, Tmus decreased to 18.1 degrees C (Tes = 37.1 degrees C), and in CB-WA, Tes decreased to 35.8 degrees C (Tmus = 34.5 degrees C). By the end of immersion, there were significant decrements (43-85%) in the performance of all tests in CB-CA and WB-CA (p < 0.0002); scores for each test were similar in these two conditions. There was no significant change in scores throughout the CB-WA condition. In both conditions with arm cooling (i.e., WB-CA and CB-CA), Tmus accounted for 85-98% of the variance in all tests. When the core was cooled in the CB-WA condition, Tes was significantly correlated to scores in only two tests (accounted for 90 and 93% of the variance) although the actual effect was small. In the CB-CA condition, partial

  3. Mesenchymal stem cells reside in a vascular niche in the decidua basalis and are absent in remodelled spiral arterioles.

    PubMed

    Kusuma, G D; Manuelpillai, U; Abumaree, M H; Pertile, M D; Brennecke, S P; Kalionis, B

    2015-03-01

    Maternal decidua basalis tissue attached to the placenta following delivery is a source of decidual mesenchymal stem cells (DMSCs). The in vitro characteristics of DMSCs have been partly defined but their in vivo function(s) are poorly understood. The anatomic location, or niche, provides clues regarding potential in vivo function(s) of DMSCs, but the niche has not been described. Cells were isolated from the decidua basalis and flow cytometric analyses showed the expected phenotypic profile for MSC cell surface markers. In vitro, the cells differentiated into adipocytes, osteocytes, and chondrocytes. DMSCs were then stained with antibodies by immunofluorescence detection. Immunocytochemistry revealed that DMSCs were positive for FZD-9, STRO-1, 3G5, and α-SMA as expected and lacked expression of vWF and Ck7. Fluorescence in situ hybridization analysis showed the cultured cells were of maternal origin. Immunofluorescence was carried out on placental bed biopsies using the FZD-9, STRO-1, 3G5, and α-SMA antibodies. DMSCs were located in the vascular niche in decidua basalis. Immunofluorescence with antibodies to FZD-9, Ck7 and vWF revealed DMSCs in the vascular niche surrounding intact non-transformed spiral arterioles but DMSCs were absent in fully transformed spiral arterioles. Spiral arteriole remodelling is a critical feature of human pregnancy. The DMSC niche was investigated in fully transformed and non-transformed spiral arterioles. DMSCs have not been previously implicated in spiral arteriole remodelling. The absence of DMSCs around fully transformed spiral arterioles suggests they are a target for replacement or destruction by invading placental extravillous trophoblast cells, which carry out spiral arteriole remodelling. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. It only takes once: The absent-exempt heuristic and reactions to comparison-based sexual risk information

    PubMed Central

    Stock, Michelle L.; Gibbons, Frederick X.; Beekman, Janine B.; Gerrard, Meg

    2015-01-01

    Three studies (N = 545) investigated the effects of social comparison on a type of heuristic called “absent-exempt” (AE; feeling exempt from future risk). Study 1 examined how comparison with an infected peer (comparison target) who was similar or non-similar in terms of sexual risk (number of partners, lack of condom use), influenced willingness and intentions to engage in sex without a condom and conditional perceived vulnerability to a sexually transmitted disease (STD). Participants generally reported lower willingness and higher conditional vulnerability if they compared with a similar-risk level target. However, high-risk students who compared with a low-risk comparison target engaged in what appeared to be AE thinking, reporting the highest willingness and lowest conditional vulnerability. Intentions to have sex without a condom were not influenced. Study 2 included a direct measure of AE thinking, and compared the impact of a low-risk comparison target with a Public Service Announcement (PSA) stating that negative outcomes (e.g., STDs) can happen even to low-risk targets. Among high-risk participants, comparing with the low-risk target led to an increase in AE thinking. As expected, the effects in Studies 1 and 2 were strongest among participants high in tendencies to socially compare. Study 3 explored whether AE thinking could be decreased by encouraging more reasoned processing. Results indicated that asking participants to think about the illogicality of AE thinking reduces AE endorsement and increases STD testing intentions. Findings suggest that comparison-based information can have a stronger influence on health cognitions than analytic-based information (e.g., most PSAs). Implications for dual-processing models of decision-making and their applicability to interventions and health messages are discussed. PMID:26098587

  5. It only takes once: The absent-exempt heuristic and reactions to comparison-based sexual risk information.

    PubMed

    Stock, Michelle L; Gibbons, Frederick X; Beekman, Janine B; Gerrard, Meg

    2015-07-01

    Three studies (N = 545) investigated the effects of social comparison on the "absent-exempt" (AE) heuristic (feeling exempt from future risk). Study 1 examined how comparison with an infected peer (comparison target) who was similar or nonsimilar in terms of sexual risk (number of partners, lack of condom use), influenced willingness and intentions to engage in sex without a condom, and conditional perceived vulnerability to an STD. Participants generally reported lower willingness and higher conditional vulnerability if they compared with a similar-risk level target. However, high-risk students who compared with a low-risk target engaged in what appeared to be AE thinking, reporting the highest willingness and lowest conditional vulnerability. Intentions to have sex without a condom were not influenced. Study 2 included a direct measure of AE thinking and compared the impact of a low-risk comparison target with a Public Service Announcement (PSA) stating that negative outcomes (STDs) can happen even to low-risk targets. Among high-risk participants, comparing with the low-risk target increased AE thinking. The effects in Studies 1 and 2 were strongest among participants high in tendencies to socially compare. Study 3 explored whether AE thinking could be decreased by encouraging more reasoned processing. Results indicated that asking participants to think about the illogicality of AE thinking reduces AE endorsement and increases STD testing intentions. Findings suggest that comparison-based information can have a stronger influence on health cognitions than analytic-based information (e.g., most PSAs). Implications for dual-processing models of decision-making and their applicability to health messages are discussed. (c) 2015 APA, all rights reserved).

  6. Cytosine DNA Methylation Is Found in Drosophila melanogaster but Absent in Saccharomyces cerevisiae, Schizosaccharomyces pombe, and Other Yeast Species

    PubMed Central

    2014-01-01

    The methylation of cytosine to 5-methylcytosine (5-meC) is an important epigenetic DNA modification in many bacteria, plants, and mammals, but its relevance for important model organisms, including Caenorhabditis elegans and Drosophila melanogaster, is still equivocal. By reporting the presence of 5-meC in a broad variety of wild, laboratory, and industrial yeasts, a recent study also challenged the dogma about the absence of DNA methylation in yeast species. We would like to bring to attention that the protocol used for gas chromatography/mass spectrometry involved hydrolysis of the DNA preparations. As this process separates cytosine and 5-meC from the sugar phosphate backbone, this method is unable to distinguish DNA- from RNA-derived 5-meC. We employed an alternative LC–MS/MS protocol where by targeting 5-methyldeoxycytidine moieties after enzymatic digestion, only 5-meC specifically derived from DNA is quantified. This technique unambiguously identified cytosine DNA methylation in Arabidopsis thaliana (14.0% of cytosines methylated), Mus musculus (7.6%), and Escherichia coli (2.3%). Despite achieving a detection limit at 250 attomoles (corresponding to <0.00002 methylated cytosines per nonmethylated cytosine), we could not confirm any cytosine DNA methylation in laboratory and industrial strains of Saccharomyces cerevisiae, Schizosaccharomyces pombe, Saccharomyces boulardii, Saccharomyces paradoxus, or Pichia pastoris. The protocol however unequivocally confirmed DNA methylation in adult Drosophila melanogaster at a value (0.034%) that is up to 2 orders of magnitude below the detection limit of bisulphite sequencing. Thus, 5-meC is a rare DNA modification in drosophila but absent in yeast. PMID:24640988

  7. ARM Airborne Carbon Measurements VI (ARM-ACME VI) Field Campaign Report

    SciTech Connect

    Biraud, Sebastien

    2017-05-01

    From October 1, 2015 through September 30, 2016, AAF deployed a Cessna 206 aircraft over the Southern Great Plains, collecting observations of trace gas mixing ratios over the ARM/SGP Central Facility. The aircraft payload included two Atmospheric Observing Systems (AOS Inc.) analyzers for continuous measurements of CO2, and a 12-flask sampler for analysis of carbon cycle gases (CO2, CO, CH4, N2O, 13CO2). The aircraft payload also includes solar/infrared radiation measurements. This research (supported by DOE ARM and TES programs) builds upon previous ARM-ACME missions. The goal of these measurements is to improve understanding of: (a) the carbon exchange of themore » ARM region; (b) how CO2 and associated water and energy fluxes influence radiative forcing, convective processes, and CO2 concentrations over the ARM region, and (c) how greenhouse gases are transported on continental scales.« less

  8. Saving Life, Limb, and Eyesight: Assessing the Medical Rules of Eligibility During Armed Conflict.

    PubMed

    Gross, Michael L

    2017-10-01

    Medical rules of eligibility permit severely injured Iraqi and Afghan nationals to receive care in Coalition medical facilities only if bed space is available and their injuries result directly from Coalition fire. The first rule favors Coalition soldiers over host-nation nationals and contradicts the principle of impartial, needs-based medical care. To justify preferential care for compatriots, wartime medicine invokes associative obligations of care that favor friends, family, and comrades-in-arms. Associative obligations have little place in peacetime medical care but significantly affect wartime medicine. The second rule suggests liability for collateral harm that is unsupported by international law and military ethics. Absent liability, there are pragmatic reasons to offer medical care to injured local civilians if it quells resentment and cements support for Coalition forces. In contrast to peacetime medicine, military necessity and associative obligations outweigh distributive principles based on medical need during war.

  9. Pitch angle of galactic spiral arms

    SciTech Connect

    Michikoshi, Shugo; Kokubo, Eiichiro, E-mail: michiko@mail.doshisha.ac.jp, E-mail: kokubo@th.nao.ac.jp

    2014-06-01

    One of the key parameters that characterizes spiral arms in disk galaxies is a pitch angle that measures the inclination of a spiral arm to the direction of galactic rotation. The pitch angle differs from galaxy to galaxy, which suggests that the rotation law of galactic disks determines it. In order to investigate the relation between the pitch angle of spiral arms and the shear rate of galactic differential rotation, we perform local N-body simulations of pure stellar disks. We find that the pitch angle increases with the epicycle frequency and decreases with the shear rate and obtain the fittingmore » formula. This dependence is explained by the swing amplification mechanism.« less

  10. Featured Image: The Birth of Spiral Arms

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2017-01-01

    In this figure, the top panels show three spiral galaxies in the Virgo cluster, imaged with the Sloan Digital Sky Survey. The bottom panels provide a comparison with three morphologically similar galaxies generated insimulations. The simulations run by Marcin Semczuk, Ewa okas, and Andrs del Pino (Nicolaus Copernicus Astronomical Center, Poland) were designed to examine how the spiral arms of galaxies like the Milky Way may have formed. In particular, the group exploredthe possibility that so-called grand-design spiral arms are caused by tidal effects as a Milky-Way-like galaxy orbits a cluster of galaxies. The authors show that the gravitational potential of the cluster can trigger the formation of two spiral arms each time the galaxy passes through the pericenter of its orbit around the cluster. Check out the original paper below for more information!CitationMarcin Semczuk et al 2017 ApJ 834 7. doi:10.3847/1538-4357/834/1/7

  11. FACE computer simulation. [Flexible Arm Controls Experiment

    NASA Technical Reports Server (NTRS)

    Sadeh, Willy Z.; Szmyd, Jeffrey A.

    1990-01-01

    A computer simulation of the FACE (Flexible Arm Controls Experiment) was conducted to assess its design for use in the Space Shuttle. The FACE is supposed to be a 14-ft long articulate structure with 4 degrees of freedom, consisting of shoulder pitch and yaw, elbow pitch, and wrist pitch. Kinematics of the FACE was simulated to obtain data on arm operation, function, workspace and interaction. Payload capture ability was modeled. The simulation indicates the capability for detailed kinematic simulation and payload capture ability analysis, and the feasibility of real-time simulation was determined. In addition, the potential for interactive real-time training through integration of the simulation with various interface controllers was revealed. At this stage, the flexibility of the arm was not yet considered.

  12. Adaptive Control Strategies for Flexible Robotic Arm

    NASA Technical Reports Server (NTRS)

    Bialasiewicz, Jan T.

    1996-01-01

    The control problem of a flexible robotic arm has been investigated. The control strategies that have been developed have a wide application in approaching the general control problem of flexible space structures. The following control strategies have been developed and evaluated: neural self-tuning control algorithm, neural-network-based fuzzy logic control algorithm, and adaptive pole assignment algorithm. All of the above algorithms have been tested through computer simulation. In addition, the hardware implementation of a computer control system that controls the tip position of a flexible arm clamped on a rigid hub mounted directly on the vertical shaft of a dc motor, has been developed. An adaptive pole assignment algorithm has been applied to suppress vibrations of the described physical model of flexible robotic arm and has been successfully tested using this testbed.

  13. Curiosity Arm Holding Steady, Sol 915

    NASA Image and Video Library

    2015-03-06

    This image from the Navigation Camera (Navcam) on NASA's Curiosity Mars rover shows the position in which the rover held its arm for several days after a transient short circuit triggered onboard fault-protection programming to halt arm activities on Feb. 27, 2015, the 911th Martian day, or sol, of the rover's work on Mars. The rover team chose to hold the arm in the same position for several days of tests to diagnose the underlying cause of the Sol 911 event. Observations with instruments on the rover's mast continued during this period. The Navcam took this image on March 4, 2015, during Sol 915. http://photojournal.jpl.nasa.gov/catalog/PIA19147

  14. ARM Unmanned Aerial Systems Implementation Plan

    SciTech Connect

    Schmid, Beat; Ivey, Mark

    Recent advances in Unmanned Aerial Systems (UAS) coupled with changes in the regulatory environment for operations of UAS in the National Airspace increase the potential value of UAS to the U.S. Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) Climate Research Facility. UAS include unmanned aerial vehicles (UAV) and tethered balloon systems (TBS). The roles UAVs and TBSs could play within the ARM Facility, particularly science questions they could help address, have been discussed in several workshops, reports, and vision documents, including: This document describes the implementation of a robust and vigorous program for use of UAV and TBS formore » the science missions ARM supports.« less

  15. Context-dependent arm pointing adaptation

    NASA Technical Reports Server (NTRS)

    Seidler, R. D.; Bloomberg, J. J.; Stelmach, G. E.

    2001-01-01

    We sought to determine the effectiveness of head posture as a contextual cue to facilitate adaptive transitions in manual control during visuomotor distortions. Subjects performed arm pointing movements by drawing on a digitizing tablet, with targets and movement trajectories displayed in real time on a computer monitor. Adaptation was induced by presenting the trajectories in an altered gain format on the monitor. The subjects were shown visual displays of their movements that corresponded to either 0.5 or 1.5 scaling of the movements made. Subjects were assigned to three groups: the head orientation group tilted the head towards the right shoulder when drawing under a 0.5 gain of display and towards the left shoulder when drawing under a 1.5 gain of display; the target orientation group had the home and target positions rotated counterclockwise when drawing under the 0.5 gain and clockwise for the 1.5 gain; the arm posture group changed the elbow angle of the arm they were not drawing with from full flexion to full extension with 0.5 and 1.5 gain display changes. To determine if contextual cues were associated with display alternations, the gain changes were returned to the standard (1.0) display. Aftereffects were assessed to determine the efficacy of the head orientation contextual cue compared to the two control cues. The head orientation cue was effectively associated with the multiple gains. The target orientation cue also demonstrated some effectiveness while the arm posture cue did not. The results demonstrate that contextual cues can be used to switch between multiple adaptive states. These data provide support for the idea that static head orientation information is a crucial component to the arm adaptation process. These data further define the functional linkage between head posture and arm pointing movements.

  16. Context-Dependent Arm Pointing Adaptation

    NASA Technical Reports Server (NTRS)

    Seidler, R. D.; Bloomberg, J. J.; Stelmach, G. E.

    2000-01-01

    We sought to determine the effectiveness of head posture as a contextual cue to facilitate adaptive transitions in manual control during visuomotor distortions. Subjects performed arm pointing movements by drawing on a digitizing tablet, with targets and movement trajectories displayed in real time on a computer monitor. Adaptation was induced by presenting the trajectories in an altered gain format on the monitor. The subjects were shown visual displays of their movements that corresponded to either 0.5 or 1.5 scaling of the movements made. Subjects were assigned to three groups: the head orientation group tilted the head towards the right shoulder when drawing under a 0.5 gain of display and towards the left shoulder when drawing under a 1.5 gain of display, the target orientation group had the home & target positions rotated counterclockwise when drawing under the 0.5 gain and clockwise for the 1.5 gain, the arm posture group changed the elbow angle of the arm they were not drawing with from full flexion to full extension with 0.5 and 1.5 gain display changes. To determine if contextual cues were associated with display alternations, the gain changes were returned to the standard (1.0) display. Aftereffects were assessed to determine the efficacy of the head orientation contextual cue. . compared to the two control cues. The head orientation cue was effectively associated with the multiple gains. The target orientation cue also demonstrated some effectiveness while the.arm posture cue did not. The results demonstrate that contextual cues can be used to switch between multiple adaptive states. These data provide support for the idea that static head orientation information is a crucial component to the arm adaptation process. These data further define the functional linkage between head posture and arm pointing movements.

  17. Characterizing Spiral Arm and Interarm Star Formation

    NASA Astrophysics Data System (ADS)

    Kreckel, K.; Blanc, G. A.; Schinnerer, E.; Groves, B.; Adamo, A.; Hughes, A.; Meidt, S.

    2016-08-01

    Interarm star formation contributes significantly to a galaxy’s star formation budget and provides an opportunity to study stellar birthplaces unperturbed by spiral arm dynamics. Using optical integral field spectroscopy of the nearby galaxy NGC 628 with VLT/MUSE, we construct Hα maps including detailed corrections for dust extinction and stellar absorption to identify 391 H II regions at 35 pc resolution over 12 kpc2. Using tracers sensitive to the underlying gravitational potential, we associate H II regions with either arm (271) or interarm (120) environments. Using our full spectral coverage of each region, we find that most physical properties (luminosity, size, metallicity, ionization parameter) of H II regions are independent of environment. We calculate the fraction of Hα luminosity due to the background of diffuse ionized gas (DIG) contaminating each H II region, and find the DIG surface brightness to be higher within H II regions than in the surroundings, and slightly higher within arm H II regions. Use of the temperature-sensitive [S II]/Hα line ratio instead of the Hα surface brightness to identify the boundaries of H II regions does not change this result. Using the dust attenuation as a tracer of the gas, we find depletion times consistent with previous work (2 × 109 yr) with no differences between the arm and interarm, but this is very sensitive to the DIG correction. Unlike molecular clouds, which can be dynamically affected by the galactic environment, we see fairly consistent properties of H II regions in both arm and interarm environments. This suggests either a difference in star formation and feedback in arms or a decoupling of dense star-forming clumps from the more extended surrounding molecular gas.

  18. CHARACTERIZING SPIRAL ARM AND INTERARM STAR FORMATION

    SciTech Connect

    Kreckel, K.; Schinnerer, E.; Meidt, S.

    2016-08-20

    Interarm star formation contributes significantly to a galaxy’s star formation budget and provides an opportunity to study stellar birthplaces unperturbed by spiral arm dynamics. Using optical integral field spectroscopy of the nearby galaxy NGC 628 with VLT/MUSE, we construct H α maps including detailed corrections for dust extinction and stellar absorption to identify 391 H ii regions at 35 pc resolution over 12 kpc{sup 2}. Using tracers sensitive to the underlying gravitational potential, we associate H ii regions with either arm (271) or interarm (120) environments. Using our full spectral coverage of each region, we find that most physical propertiesmore » (luminosity, size, metallicity, ionization parameter) of H ii regions are independent of environment. We calculate the fraction of H α luminosity due to the background of diffuse ionized gas (DIG) contaminating each H ii region, and find the DIG surface brightness to be higher within H ii regions than in the surroundings, and slightly higher within arm H ii regions. Use of the temperature-sensitive [S ii]/H α line ratio instead of the H α surface brightness to identify the boundaries of H ii regions does not change this result. Using the dust attenuation as a tracer of the gas, we find depletion times consistent with previous work (2 × 10{sup 9} yr) with no differences between the arm and interarm, but this is very sensitive to the DIG correction. Unlike molecular clouds, which can be dynamically affected by the galactic environment, we see fairly consistent properties of H ii regions in both arm and interarm environments. This suggests either a difference in star formation and feedback in arms or a decoupling of dense star-forming clumps from the more extended surrounding molecular gas.« less

  19. MPL-net at ARM Sites

    NASA Technical Reports Server (NTRS)

    Spinhirne, J. D.; Welton, E. J.; Campbell, J. R.; Berkoff, T. A.; Starr, David OC. (Technical Monitor)

    2002-01-01

    The NASA MPL-net project goal is consistent data products of the vertical distribution of clouds and aerosol from globally distributed lidar observation sites. The four ARM micro pulse lidars are a basis of the network to consist of over twelve sites. The science objective is ground truth for global satellite retrievals and accurate vertical distribution information in combination with surface radiation measurements for aerosol and cloud models. The project involves improvement in instruments and data processing and cooperation with ARM and other partners.

  20. Crew Access Arm arrival at Mobile Launcher

    NASA Image and Video Library

    2017-11-09

    A heavy-load transport truck carrying the Orion crew access arm arrives at the mobile launcher (ML) at NASA's Kennedy Space Center in Florida. The crew access arm will be installed at about the 274-foot level on the mobile launcher tower. It will rotate from its retracted position and interface with the Orion crew hatch location to provide entry to the Orion crew module. The Ground Systems Development and Operations Program is overseeing installation of umbilicals and launch accessories on the ML tower to prepare for Exploration Mission-1.

  1. Crew Access Arm Installation onto Mobile Launcher

    NASA Image and Video Library

    2018-02-24

    At NASA's Kennedy Space Center in Florida, the Orion crew access arm (CAA) is lifted and attached to the Mobile Launcher (ML). The arm is installed at about the 274-foot level on the ML tower. NASA's Exploration Ground Systems organization has been overseeing installation of umbilicals and other launch accessories on the 380-foot-tall ML in preparation for stacking the first launch of the Space launch System (SLS), rocket with an Orion spacecraft. The CAA is designed to rotate from its retracted position and line up with Orion's crew hatch providing entry for astronauts and technicians.

  2. Crew Access Arm Install on Mobile Launcher

    NASA Image and Video Library

    2018-02-24

    At NASA's Kennedy Space Center in Florida, the Orion crew access arm (CAA) is lifted and attached to the Mobile Launcher (ML). The arm is installed at about the 274-foot level on the ML tower. NASA's Exploration Ground Systems organization has been overseeing installation of umbilicals and other launch accessories on the 380-foot-tall ML in preparation for stacking the first launch of the Space launch System (SLS), rocket with an Orion spacecraft. The CAA is designed to rotate from its retracted position and line up with Orion's crew hatch providing entry for astronauts and technicians.

  3. Two-Armed, Mobile, Sensate Research Robot

    NASA Technical Reports Server (NTRS)

    Engelberger, J. F.; Roberts, W. Nelson; Ryan, David J.; Silverthorne, Andrew

    2004-01-01

    The Anthropomorphic Robotic Testbed (ART) is an experimental prototype of a partly anthropomorphic, humanoid-size, mobile robot. The basic ART design concept provides for a combination of two-armed coordination, tactility, stereoscopic vision, mobility with navigation and avoidance of obstacles, and natural-language communication, so that the ART could emulate humans in many activities. The ART could be developed into a variety of highly capable robotic assistants for general or specific applications. There is especially great potential for the development of ART-based robots as substitutes for live-in health-care aides for home-bound persons who are aged, infirm, or physically handicapped; these robots could greatly reduce the cost of home health care and extend the term of independent living. The ART is a fully autonomous and untethered system. It includes a mobile base on which is mounted an extensible torso topped by a head, shoulders, and two arms. All subsystems of the ART are powered by a rechargeable, removable battery pack. The mobile base is a differentially- driven, nonholonomic vehicle capable of a speed >1 m/s and can handle a payload >100 kg. The base can be controlled manually, in forward/backward and/or simultaneous rotational motion, by use of a joystick. Alternatively, the motion of the base can be controlled autonomously by an onboard navigational computer. By retraction or extension of the torso, the head height of the ART can be adjusted from 5 ft (1.5 m) to 6 1/2 ft (2 m), so that the arms can reach either the floor or high shelves, or some ceilings. The arms are symmetrical. Each arm (including the wrist) has a total of six rotary axes like those of the human shoulder, elbow, and wrist joints. The arms are actuated by electric motors in combination with brakes and gas-spring assists on the shoulder and elbow joints. The arms are operated under closed-loop digital control. A receptacle for an end effector is mounted on the tip of the wrist and

  4. Crew Access Arm Installation onto Mobile Launcher

    NASA Image and Video Library

    2018-02-24

    At NASA's Kennedy Space Center in Florida, a crane is prepared to lift the Orion crew access arm (CAA) so it can be attached to the mobile launcher (ML). The arm will be installed at about the 274-foot level on the ML tower. NASA's Exploration Ground Systems organization has been overseeing installation of umbilicals and other launch accessories on the 380-foot-tall ML in preparation for stacking the first launch of the Space launch System, or SLS, rocket with an Orion spacecraft. The CAA is designed to rotate from its retracted position and line up with Orion's crew hatch providing entry for astronauts and technicians.

  5. Crew Access Arm Installation onto Mobile Launcher

    NASA Image and Video Library

    2018-02-26

    At NASA's Kennedy Space Center in Florida, a crane positions the Orion crew access arm (CAA) so it can be attached to the mobile launcher (ML). The arm will be installed at about the 274-foot level on the ML tower. NASA's Exploration Ground Systems organization has been overseeing installation of umbilicals and other launch accessories on the 380-foot-tall ML in preparation for stacking the first launch of the Space launch System (SLS), rocket with an Orion spacecraft. The CAA is designed to rotate from its retracted position and line up with Orion's crew hatch providing entry for astronauts and technicians.

  6. Crew Access Arm Installation onto Mobile Launcher

    NASA Image and Video Library

    2018-02-26

    Under the watchful eye of technicians and engineers, a crane begins lifting the Orion crew access arm (CAA) so it can be attached to the mobile launcher (ML) at NASA's Kennedy Space Center in Florida. The arm will be installed at about the 274-foot level on the ML tower. NASA's Exploration Ground Systems organization has been overseeing installation of umbilicals and other launch accessories on the 380-foot-tall ML in preparation for stacking the first launch of the Space launch System (SLS), rocket with an Orion spacecraft. The CAA is designed to rotate from its retracted position and line up with Orion's crew hatch providing entry for astronauts and technicians.

  7. Crew Access Arm Installation onto Mobile Launcher

    NASA Image and Video Library

    2018-02-26

    At NASA's Kennedy Space Center in Florida, a crane lifts the Orion crew access arm (CAA) so it can be attached to the mobile launcher (ML). The arm will be installed at about the 274-foot level on the ML tower. NASA's Exploration Ground Systems organization has been overseeing installation of umbilicals and other launch accessories on the 380-foot-tall ML in preparation for stacking the first launch of the Space launch System (SLS), rocket with an Orion spacecraft. The CAA is designed to rotate from its retracted position and line up with Orion's crew hatch providing entry for astronauts and technicians.

  8. Crew Access Arm Installation onto Mobile Launcher

    NASA Image and Video Library

    2018-02-26

    At NASA's Kennedy Space Center in Florida, technicians assist as a crane lifts the Orion crew access arm (CAA) so it can be attached to the mobile launcher (ML). The arm will be installed at about the 274-foot level on the ML tower. NASA's Exploration Ground Systems organization has been overseeing installation of umbilicals and other launch accessories on the 380-foot-tall ML in preparation for stacking the first launch of the Space launch System (SLS), rocket with an Orion spacecraft. The CAA is designed to rotate from its retracted position and line up with Orion's crew hatch providing entry for astronauts and technicians.

  9. Crew Access Arm Installation onto Mobile Launcher

    NASA Image and Video Library

    2018-02-26

    At NASA's Kennedy Space Center in Florida, a crane begins lifting the Orion crew access arm (CAA) so it can be attached to the mobile launcher (ML). The arm will be installed at about the 274-foot level on the ML tower. NASA's Exploration Ground Systems organization has been overseeing installation of umbilicals and other launch accessories on the 380-foot-tall ML in preparation for stacking the first launch of the Space launch System (SLS), rocket with an Orion spacecraft. The CAA is designed to rotate from its retracted position and line up with Orion's crew hatch providing entry for astronauts and technicians.

  10. The quest for the bionic arm.

    PubMed

    Hutchinson, Douglas T

    2014-06-01

    The current state of research of upper extremity prosthetic devices is focused on creating a complete prosthesis with full motor and sensory function that will provide amputees with a near-normal human arm. Although advances are being made rapidly, many hurdles remain to be overcome before a functional, so-called bionic arm is a reality. Acquiring signals via nerve or muscle inputs will require either a reliable wireless device or direct wiring through an osseous-integrated implant. The best way to tap into the "knowledge" present in the peripheral nerve is yet to be determined. Copyright 2014 by the American Academy of Orthopaedic Surgeons.

  11. The arms race and nuclear war

    SciTech Connect

    Barash, D.P.

    Addressing the history, physics, biology, economics, politics, psychology, and ethics of nuclear armaments, the author provides a survey of diverse facets of the nuclear controversy. The study encompasses such key areas as nuclear hardware and technology; the short- and long-term effects of nuclear weapons; strategic doctrine, deterrence and defense policy; the arms race, arms control, and nuclear proliferation; and the economic impact, psychology, and ethics of nuclear armaments. A ''Policy Issues'' section, presenting both the advocate and opponent sides of the debate, is included with each chapter.

  12. Neurobiology: motor control of flexible octopus arms.

    PubMed

    Sumbre, Germán; Fiorito, Graziano; Flash, Tamar; Hochner, Binyamin

    2005-02-10

    Animals with rigid skeletons can rely on several mechanisms to simplify motor control--for example, they have skeletal joints that reduce the number of variables and degrees of freedom that need to be controlled. Here we show that when the octopus uses one of its long and highly flexible arms to transfer an object from one place to another, it employs a vertebrate-like strategy, temporarily reconfiguring its arm into a stiffened, articulated, quasi-jointed structure. This indicates that an articulated limb may provide an optimal solution for achieving precise, point-to-point movements.

  13. Reciprocal selection causes a coevolutionary arms race between crossbills and lodgepole pine.

    PubMed

    Benkman, Craig W; Parchman, Thomas L; Favis, Amanda; Siepielski, Adam M

    2003-08-01

    Few studies have shown both reciprocal selection and reciprocal adaptations for a coevolving system in the wild. The goal of our study was to determine whether the patterns of selection on Rocky Mountain lodgepole pine (Pinus contorta spp. latifolia) and red crossbills (Loxia curvirostra complex) were concordant with earlier published evidence of reciprocal adaptations in lodgepole pine and crossbills on isolated mountain ranges in the absence of red squirrels (Tamiasciurus hudsonicus). We found that selection (directional) by crossbills on lodgepole pine where Tamiasciurus are absent was divergent from the selection (directional) exerted by Tamiasciurus on lodgepole pine. This resulted in divergent selection between areas with and without Tamiasciurus that was congruent with the geographic patterns of cone variation. In the South Hills, Idaho, where Tamiasciurus are absent and red crossbills are thought to be coevolving with lodgepole pine, crossbills experienced stabilizing selection on bill size, with cone structure as the agent of selection. These results show that crossbills and lodgepole pine exhibit reciprocal adaptations in response to reciprocal selection, and they provide insight into the traits mediating and responding to selection in a coevolutionary arms race.

  14. The absent discourse of communication: understanding ethics of provider-patient relationship in six hospitals in urban India

    PubMed Central

    Ghoshal, Rakhi; Madhiwalla, Neha; Jesani, Amar; Samant, Padmaja; Badhwar, Vijaya; Surve, Sweta

    2013-01-01

    Understanding the complexities of a provider-patient relationship is considered to be of critical importance especially in medical ethics. It is important to understand this relation from the perspectives of all stakeholders. This article derives from a qualitative study conducted across six obstetric care providing institutions in the cities of Mumbai and Navi Mumbai, India, over a period of 10 months. Thirty obstetricians were interviewed in-depth to understand what they perceived as the most important aspect in developing a good provider-patient relationship. The study found that while most providers highlighted the point of communication as the most critical part of the provider-patient relationship, they admitted that they could not engage in communication with the patients for various reasons. Obstetric consultants and residents said that they were too overburdened to spend time communicating with patients; providers working in public hospitals added that the lack of education of their patients posed a hindrance in effective communication. However, providers practicing in private institutions explained that they faced a challenge in communicating with patients because their patients came from educated families who tended to trust the provider less and were generally more critical of the provider’s clinical judgement. The article shows how provider-patient communication exists as an idea among medical providers but is absent in daily clinical practice. This gives rise to a discourse shaped around an absence. The authors conclude by decoding the term ‘communication’ – they read the word against the context of its use in the interviews, and argue that for the providers ‘communication’ was not intended to be a trope towards setting up a dialogue-based, egalitarian provider-patient relationship. Providers used the word in lieu of ‘counselling’, ‘guiding’, ‘talking to’. It concludes that, despite the providers’ insisting on the

  15. Absent mandibular gap in the retronasal triangle view: a clue to the diagnosis of micrognathia in the first trimester.

    PubMed

    Sepulveda, W; Wong, A E; Viñals, F; Andreeva, E; Adzehova, N; Martinez-Ten, P

    2012-02-01

    To describe a new ultrasound technique that may be useful for the diagnosis of micrognathia in the first trimester of pregnancy. The retronasal triangle (RNT) view is a technique that captures the coronal plane of the face in which the primary palate and the frontal processes of the maxilla are visualized simultaneously. Normal first-trimester fetuses display a characteristic gap between the right and left body of the mandible in this view (the 'mandibular gap'). The presence or absence of this gap was evaluated and measured prospectively during real-time scanning (n = 154) and retrospectively by analyzing three-dimensional (3D) datasets (n = 50) in normal first-trimester fetuses undergoing screening for aneuploidy at 11-13 weeks' gestation. 3D datasets from 12 fetuses with suspected micrognathia were also collected and examined retrospectively for the same features. The mandibular gap was identified in all 204 normal fetuses and increased linearly with increasing crown-rump length (y = 0.033x + 0.435; R(2) = 0.316), with no statistically significant differences between measurements obtained by two-dimensional ultrasound and 3D offline analysis. Among fetuses with suspected micrognathia, three 3D datasets were excluded from analysis because of poor image quality in one and the diagnosis of a normal chin in two. In the remaining nine fetuses, the mandibular gap was absent and was replaced by a bony structure representing the receding chin in seven (77.8%) cases and was not visualized due to severe retrognathia in the remaining two (22.2%) cases. All fetuses with micrognathia had associated anomalies, including seven with aneuploidy and two with skeletal dysplasia. The RNT view may be a helpful technique for detecting micrognathia in the first trimester. The absence of the mandibular gap or failure to identify the mandible in this view is highly suggestive of micrognathia and should prompt a targeted ultrasound scan to assess for other anomalies. Further research is

  16. The Apocalyptic Premise: Nuclear Arms Debated.

    ERIC Educational Resources Information Center

    Lefever, Ernest W., Ed.; Hunt, E. Stephen, Ed.

    This document contains 31 position papers that reflect a wide range of views on nuclear arms policy held by political leaders, religious authorities, scholars, policy experts, journalists, and political activists. Since no judgments are made, the reader is left to decide which arguments are most compelling. Each position paper is arranged into one…

  17. 49 CFR 236.702 - Arm, semaphore.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Arm, semaphore. 236.702 Section 236.702 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION..., semaphore. The part of a semaphore signal displaying an aspect. It consists of a blade fastened to a...

  18. Educating Policymakers: 2006 NPS Arms Educators

    ERIC Educational Resources Information Center

    Techniques: Connecting Education and Careers, 2006

    2006-01-01

    This article reports that at the 2006 ACTE National Policy Seminar, nearly 500 career and technical educators gathered in Washington, DC, in March to learn about what is happening with Perkins, receive tips on working with the media, and voice their opinions with their federal representatives. Attendees left this session armed with the statistics…

  19. Accreditation for Armed Forces Educational Institutions.

    ERIC Educational Resources Information Center

    Tarquine, Robert Blaine

    The report established the need for educational accreditation and consolidates the various means of achieving accreditation that are available to the Armed Forces, into one accessible reference. The scope of each accrediting method is presented in detail, allowing educational officials to evaluate the methods in respect to their individual…

  20. STRUCTURED MOLECULAR GAS REVEALS GALACTIC SPIRAL ARMS

    SciTech Connect

    Sawada, Tsuyoshi; Hasegawa, Tetsuo; Koda, Jin, E-mail: sawada.tsuyoshi@nao.ac.jp

    We explore the development of structures in molecular gas in the Milky Way by applying the analysis of the brightness distribution function and the brightness distribution index (BDI) in the archival data from the Boston University-Five College Radio Astronomy Observatory {sup 13}CO J = 1-0 Galactic Ring Survey. The BDI measures the fractional contribution of spatially confined bright molecular emission over faint emission extended over large areas. This relative quantity is largely independent of the amount of molecular gas and of any conventional, pre-conceived structures, such as cores, clumps, or giant molecular clouds. The structured molecular gas traced by highermore » BDI is located continuously along the spiral arms in the Milky Way in the longitude-velocity diagram. This clearly indicates that molecular gas changes its structure as it flows through the spiral arms. Although the high-BDI gas generally coincides with H II regions, there is also some high-BDI gas with no/little signature of ongoing star formation. These results support a possible evolutionary sequence in which unstructured, diffuse gas transforms itself into a structured state on encountering the spiral arms, followed by star formation and an eventual return to the unstructured state after the spiral arm passage.« less

  1. RMS arm extended over Earth view

    NASA Image and Video Library

    2005-08-02

    ISS011-E-11414 (2 August 2005) --- A line of thunderstorms form the backdrop for this view of the extended Space Shuttle Discovery’s remote manipulator system (RMS) robotic arm while docked to the International Space Station during the STS-114 mission.

  2. Neurosurgical robotic arm drilling navigation system.

    PubMed

    Lin, Chung-Chih; Lin, Hsin-Cheng; Lee, Wen-Yo; Lee, Shih-Tseng; Wu, Chieh-Tsai

    2017-09-01

    The aim of this work was to develop a neurosurgical robotic arm drilling navigation system that provides assistance throughout the complete bone drilling process. The system comprised neurosurgical robotic arm navigation combining robotic and surgical navigation, 3D medical imaging based surgical planning that could identify lesion location and plan the surgical path on 3D images, and automatic bone drilling control that would stop drilling when the bone was to be drilled-through. Three kinds of experiment were designed. The average positioning error deduced from 3D images of the robotic arm was 0.502 ± 0.069 mm. The correlation between automatically and manually planned paths was 0.975. The average distance error between automatically planned paths and risky zones was 0.279 ± 0.401 mm. The drilling auto-stopping algorithm had 0.00% unstopped cases (26.32% in control group 1) and 70.53% non-drilled-through cases (8.42% and 4.21% in control groups 1 and 2). The system may be useful for neurosurgical robotic arm drilling navigation. Copyright © 2016 John Wiley & Sons, Ltd.

  3. 32 CFR 935.134 - Arm signals.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... making a turn or coming to a stop shall signal the turn or stop in accordance with this section. (b) A... downward. (c) A signal light or other device may be used in place of an arm signal prescribed in paragraph...

  4. 32 CFR 935.134 - Arm signals.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... making a turn or coming to a stop shall signal the turn or stop in accordance with this section. (b) A... downward. (c) A signal light or other device may be used in place of an arm signal prescribed in paragraph...

  5. HOW TO PASS ARMED FORCES TESTS.

    ERIC Educational Resources Information Center

    Cowles Education Corp., New York, NY.

    FOLLOWING THE CONTENT OF THE ARMED FORCES EXAMINATIONS, THIS BOOK IS PROGRAMED WITH STEP-BY-STEP DIRECTIONS, TESTS, AND CORRECT ANSWERS AND SOLUTIONS. THE CANDIDATE CAN SIMULATE TAKING THE ACTUAL EXAMS BY ANSWERING THE AUTHENTIC QUESTIONS AND PROBLEMS, MARKING THE ANSWER SHEET, AND EVALUATING HIS OWN APTITUDE BY COMPARING HIS ANSWERS WITH THE…

  6. 75 FR 28185 - Armed Forces Day, 2010

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-20

    ... Forces Day, 2010 By the President of the United States of America A Proclamation America's Armed Forces... that have sustained us from our earliest days of independence. Today, we have the greatest military.... We are also increasing support for military spouses and families who must deal with the stress and...

  7. 77 FR 30875 - Armed Forces Day, 2012

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-23

    ... Forces Day, 2012 By the President of the United States of America A Proclamation With every assignment and in every theater, America's men and women in uniform perform their duties with the utmost dignity... at their homes on Armed Forces Day, and I urge citizens to learn more about military service by...

  8. Colleges Grapple with the "Behavioral Broken Arm"

    ERIC Educational Resources Information Center

    Hoover, Eric

    2008-01-01

    After the fatal shootings at Virginia Tech last April, colleges went shopping for hardware. They bought sirens, mass-messaging systems, surveillance cameras, and door locks. Some colleges armed their police departments for the first time. Others added assault rifles to their arsenals. "Active shooter" drills happened everywhere. As administrators…

  9. ARM Madden-Julian Oscillation Investigation Experiment

    ScienceCinema

    Long, Chuck

    2018-06-06

    Results of the ARM Madden-Julian Oscillation (MJO) Investigation Experiment (AMIE) field campaign are contributing significantly to concurrent national and international research efforts addressing questions about how the MJO initiates and changes as it passes phenomenon differs in observations versus models.

  10. Quantitative analysis of arm movement smoothness

    NASA Astrophysics Data System (ADS)

    Szczesna, Agnieszka; Błaszczyszyn, Monika

    2017-07-01

    The paper deals with the problem of motion data quantitative smoothness analysis. We investigated values of movement unit, fluidity and jerk for healthy and paralyzed arm of patients with hemiparesis after stroke. Patients were performing drinking task. To validate the approach, movement of 24 patients were captured using optical motion capture system.

  11. Mars Rover Curiosity Arm Held High

    NASA Image and Video Library

    2011-06-13

    This photograph of the NASA Mars Science Laboratory rover, Curiosity, was taken during testing on June 3, 2011. The turret at the end of Curiosity robotic arm holds five devices. In this view, the drill is at the six oclock position.

  12. Color Camera for Curiosity Robotic Arm

    NASA Image and Video Library

    2010-11-16

    The Mars Hand Lens Imager MAHLI camera will fly on NASA Mars Science Laboratory mission, launching in late 2011. This photo of the camera was taken before MAHLI November 2010 installation onto the robotic arm of the mission Mars rover, Curiosity.

  13. Vibrations in a moving flexible robot arm

    NASA Technical Reports Server (NTRS)

    Wang, P. K. C.; Wei, Jin-Duo

    1987-01-01

    The vibration in a flexible robot arm modeled by a moving slender prismatic beam is considered. It is found that the extending and contracting motions have destabilizing and stabilizing effects on the vibratory motions, respectively. The vibration analysis is based on a Galerkin approximation with time-dependent basis functions. Typical numerical results are presented to illustrate the qualitative features of vibrations.

  14. Instructional Technology in the Armed Forces.

    ERIC Educational Resources Information Center

    Hitchens, Howard B., Jr.

    Broad areas of communications media used in technical training in specific occupational skills within the armed forces are examined in the first part of this report. These areas include: traditional audiovisual media, television, the techniques of programed instruction and instructional systems development, and the use of computers. In the second…

  15. Arms Control, Disarmament, and Peace Newsletters.

    ERIC Educational Resources Information Center

    Atkins, Stephen

    1986-01-01

    Considers the research value of four types of newsletters on arms control, disarmament, and peace: direct-action, informational, scholarly, and single-issue. An annotated list of 58 newsletters includes those considered most significant of their type and recommended for library collections. (EM)

  16. Psychologists' Attitudes and Behaviors Regarding Nuclear Arms.

    ERIC Educational Resources Information Center

    McConnell, Stephen C.; And Others

    This survey examined the attitudes and behaviors of the 297 members of the American Psychological Association (APA) who responded to a mail survey of 1,000 members concerning a 1982 APA resolution calling for a nuclear freeze, a return to a productive civilian economy, and other issues related to nuclear arms. The attitudes and behaviors of the…

  17. ATM Substrate Chk2-interacting Zn2+ Finger (ASCIZ) Is a Bi-functional Transcriptional Activator and Feedback Sensor in the Regulation of Dynein Light Chain (DYNLL1) Expression*

    PubMed Central

    Jurado, Sabine; Conlan, Lindus A.; Baker, Emma K.; Ng, Jane-Lee; Tenis, Nora; Hoch, Nicolas C.; Gleeson, Kimberly; Smeets, Monique; Izon, David; Heierhorst, Jörg

    2012-01-01

    The highly conserved DYNLL1 (LC8) protein was originally discovered as a light chain of the dynein motor complex, but is increasingly emerging as a sequence-specific regulator of protein dimerization with hundreds of targets and wide-ranging cellular functions. Despite its important roles, DYNLL1's own regulation remains poorly understood. Here we identify ASCIZ (ATMIN/ZNF822), an essential Zn2+ finger protein with dual roles in the DNA base damage response and as a developmental transcription factor, as a conserved regulator of Dynll1 gene expression. DYNLL1 levels are reduced by ∼10-fold in the absence of ASCIZ in human, mouse and chicken cells. ASCIZ binds directly to the Dynll1 promoter and regulates its activity in a Zn2+ finger-dependent manner. DYNLL1 protein in turn interacts with ten binding sites in the ASCIZ transcription activation domain, and high DYNLL1 levels inhibit the transcriptional activity of ASCIZ. In addition, DYNLL1 was also required for DNA damage-induced ASCIZ focus formation. The dual ability of ASCIZ to activate Dynll1 gene expression and to sense free DYNLL1 protein levels enables a simple dynamic feedback loop to adjust DYNLL1 levels to cellular needs. The ASCIZ-DYNLL1 feedback loop represents a novel mechanism for auto-regulation of gene expression, where the gene product directly inhibits the transcriptional activator while bound at its own promoter. PMID:22167198

  18. Effect of daily sildenafil on patients with absent nocturnal erections due to pelvic fracture urethral disruption: a single-centre experience.

    PubMed

    Peng, J; Zhang, Z; Gao, B; Yuan, Y; Cui, W; Tang, Y; Song, W; Xin, Z

    2016-12-01

    Erectile dysfunction (ED) is a common sequel of pelvic fracture urethral disruption. Those patients with nocturnal erections may respond favourably to sildenafil; however, little is known about the response to sildenafil in patients with absent nocturnal erections. The aim was to evaluate the response to the treatment of sildenafil 50 mg taken once daily in the patients with absent nocturnal erections. From January 2008 to December 2011, a total of 28 patients with absent nocturnal erections were evaluated. We recorded nocturnal penile tumescence and rigidity with an erectometer. If nocturnal erections were absent for three nights, patients were administrated sildenafil 100 mg at bedtime and tested again at the fourth night. Penile duplex ultrasound with intracavernous injection was performed to define the cause of ED. All patients received a daily dose of sildenafil 50 mg for 12 weeks. Response to sildenafil treatment was defined as sustained erections allowing vaginal penetration and intercourse. Twenty-three (78%) patients completed the daily sildenafil treatment, and follow-up was available. The nocturnal erections at the fourth night in 13 patients (46.4%) were improved. About 61.5% (8/13) reported effective response to daily sildenafil. The improvement of nocturnal erections induced by sildenafil taken at bedtime might predict the response to sildenafil taken daily. © 2016 Blackwell Verlag GmbH.

  19. Finding the Two-Way Street: Women from Mother-Present/Father-Absent Homes and Their Ability to Make Close Female Friendships

    ERIC Educational Resources Information Center

    Marote, Melissa A.

    2011-01-01

    This heuristic study involving seven coresearchers, which included the author, explores the experiences of women from mother-present/father-absent homes and their ability to form and maintain close female friendships. The heuristic research model was chosen to provide the opportunity to conduct research in a very personalized, collaborative way…

  20. Tracing the Arms of our Milky Way Galaxy

    NASA Image and Video Library

    2015-06-03

    Astronomers using data from NASA's Wide-field Infrared Survey Explorer, or WISE, are helping to trace the shape of our Milky Way galaxy's spiral arms. This illustration shows where WISE data revealed clusters of young stars shrouded in dust, called embedded clusters, which are known to reside in spiral arms. The bars represent uncertainties in the data. The nearly 100 clusters shown here were found in the arms called Perseus, Sagittarius-Carina, and Outer -- three of the galaxy's four proposed primary arms. Our sun resides in a spur to an arm, or a minor arm, called Orion Cygnus. http://photojournal.jpl.nasa.gov/catalog/PIA19341