Symmetries in bacterial motility

Descriptions are given of three kinds of symmetries encountered in studies of bacterial locomotion, and of the ways in which they are circumvented or broken. A bacterium swims at very low Reynolds number: it cannot propel itself using reciprocal motion (by moving through a sequence of shapes, first forward and then in reverse); cyclic motion is required. A common solution is rotation of a helical filament, either right- or left-handed. The flagellar rotary motor that drives each filament generates the same torque whether spinning clockwise or counterclockwise. This symmetry is broken by coupling to the filament. Finally, bacterial populations, grown in a nutrient medium from an inoculum placed at a single point, usually move outward in symmetric circular rings. Under certain conditions, the cells excrete a chemoattractant, and the rings break up into discrete aggregates that can display remarkable geometric order.

Retro and retroenantio analogs of cecropin-melittin hybrids.

Hybrid analogs of cecropin A (CA) and melittin (M), which are potent antibacterial peptides, have been synthesized. To understand the structural requirements for this antibacterial activity, we have also synthesized the enantio, retro, and retroenantio isomers of two of the hybrids and their N-terminally acetylated derivatives. All analogs of CA(1-13)M(1-13)-NH2 were as active as the parent peptide against five test bacterial strains, but one bacterial strain was resistant to the retro and retroenantio derivatives. Similarly, all analogs of CA(1-7)M(2-9)-NH2 were active against four strains, while two strains were resistant to the retro and retroenantio analogs containing free NH3+ end groups, but acetylation restored activity against one of them. From these data it was concluded that chirality of the peptide was not a critical feature, and full activity could be achieved with peptides containing either all L- or all D-amino acids in their respective right-handed or left-handed helical conformations. For most of the bacterial strains, the sequence of these peptides or the direction of the peptide bonds could be critical but not both at the same time. For some strains, both needed to be conserved.

The Structure of theCyprinid herpesvirus 3ORF112-Zα·Z-DNA Complex Reveals a Mechanism of Nucleic Acids Recognition Conserved with E3L, a Poxvirus Inhibitor of Interferon Response

In vertebrate species, the innate immune system down-regulates protein translation in response to viral infection through the action of the double-stranded RNA (dsRNA)-activated protein kinase (PKR). In some teleost species another protein kinase, Z-DNA-dependent protein kinase (PKZ), plays a similar role but instead of dsRNA binding domains, PKZ has Zα domains. These domains recognize the left-handed conformer of dsDNA and dsRNA known as Z-DNA/Z-RNA. Cyprinid herpesvirus 3 infects common and koi carp, which have PKZ, and encodes the ORF112 protein that itself bears a Zα domain, a putative competitive inhibitor of PKZ. Here we present the crystal structure of ORF112-Zα in complex with an 18-bp CpG DNA repeat, at 1.5 Å. We demonstrate that the bound DNA is in the left-handed conformation and identify key interactions for the specificity of ORF112. Localization of ORF112 protein in stress granules induced in Cyprinid herpesvirus 3-infected fish cells suggests a functional behavior similar to that of Zα domains of the interferon-regulated, nucleic acid surveillance proteins ADAR1 and DAI.

Zalpha-domains: At the intersection between RNA editing and innate immunity

The involvement of A to I RNA editing in antiviral responses was first indicated by the observation of genomic hyper-mutation for several RNA viruses in the course of persistent infections. However, in only a few cases an antiviral role was ever demonstrated and surprisingly, it turns out that ADARs - the RNA editing enzymes - may have a prominent pro-viral role through the modulation/down-regulation of the interferon response. A key role in this regulatory function of RNA editing is played by ADAR1, an interferon inducible RNA editing enzyme. A distinguishing feature of ADAR1, when compared with other ADARs, is the presence of a Z-DNA binding domain, Zalpha. Since the initial discovery of the specific and high affinity binding of Zalpha to CpG repeats in a left-handed helical conformation, other proteins, all related to the interferon response pathway, were shown to have similar domains throughout the vertebrate lineage. What is the biological function of this domain family remains unclear but a significant body of work provides pieces of a puzzle that points to an important role of Zalpha domains in the recognition of foreign nucleic acids in the cytoplasm by the innate immune system. Here we will provide an overview of our knowledge on ADAR1 function in interferon response with emphasis on Zalpha domains.

Tales from "Blackwood"; being the most famous series of stories ever published, especially selected from that celebrated English publication.

v.l. Francillon, R.E. Left-handed Elsa. The great earthquake at Lisbon. Lever, Charles. Some one pays. Sir Tray: an Arthurian idyl.--v.2. Hamley, E.B. Shakespeare's funeral. Lockhart, L.W.M. A night with the Volunteers of Strathkinahan. The philosopher's baby. Oliphant, M.O.W. The secret chamber.--v.3 Majendle, Lady Margaret. A French speculation. Moncrieff, H.J. Rufus Hickman of St. Botolph's. Lewis. C.L. Hans Preller: a legend of the Rhine falls. Kingsley, Maurice. The Puerto de Medina. Harcourt, Alfred. Jack and Minory.--v.4. Considine, Bob. What I did at Belgrade. Shand, A.I. Wrecked off the Riff coast. Dollie and the two Smiths. Majendle, Lady Margaret. A railway journey.--v.5. The missing bills: an unsolved mystery. Cheadle, W.B. My hunt of the silver fox. Narrative of Prince Charlie's escape, by one of his companions. A Fenian alarm. Lindau, Rudolph. The philosopher's pendulum.--v.6. The battle of Dorking. Late for the train. Aytoun, W.E. ...

The plays and poems of William Shakspeare,

Edited by James Boswell, the younger, to whom Malone left his materials for a new edition (Malone's first edition appeared in 1790 in 10 vols.) " 'Boswell's Malone'is generally known as the 'third variorum' edition of Shakespeare." cf. Dict. nat. biog. v. 35, p. 437.

Distortion product otoacoustic emissions in school children: Effects to gender, ear asymmetry and handedness

Accurate interpretation of distortion product otoacoustic emission (DPOAE) data cannot be made without realizing the effects of non-pathological factors on DPOAEs. The present study aimed to examine the effects of ear asymmetry, gender and handedness on DPOAEs obtained from school children. One thousand and three children (528 boys and 475 girls) with a mean age of 6.2 years (SD = 0.4, range = 5.2 7.9 years) were tested in a quiet room at their schools using the GSI-60 DPOAE system. The stimuli consisted of two pure tones of different frequencies f1 and f2 presented at 65 and 55dB SPL respectively. A DP-gram was obtained for each ear with f2 varying from 1.1 to 6.0 kHz and the ratio of f2/f1 being kept at 1.21. The signal-to-noise ratios (SNR) (DPOAE amplitude minus the mean noise floor) at the tested frequencies 1.1, 1.5, 1.9, 2.4, 3.0, 3.8, 4.8, and 6.0 kHz were measured. The results revealed a small, but significant difference in SNR between ears, with right ears showing a higher mean SNR than left ears at 1.9, 3.0, 3.8 and 6.0 kHz. At these frequencies, the difference in mean SNR between ears was less than 1 dB. A significant gender effect was also found, with girls exhibiting a higher SNR than boys at 3.8, 4.8 and 6.0 kHz. The difference in mean SNR, as a result of the gender effect, was about 1 to 2 dB at these frequencies. The results from the present study indicated no significant difference in mean SNR between left-handed and right-handed children for all tested frequencies. In conclusion, these non-pathological characteristics of DPOAEs should be considered in the interpretation of DPOAE results for school children.

What one hand giveth the other taketh away:some unpredicted effects of enantiomers in psychopharmacology

It is well known that many medicines are a mixture of two enantiomers, or mirror-image molecules. Two enantiomers occur when a molecule has a single chiral centre and the two mirror images, called S or L (left handed) and R or D (right handed), are usually found in equal amounts in the parent (racemic) mixture. While for many compounds used in clinical practice the active moiety is found in one of the two enantiomers with the other being seen as an unnecessary and redundant component of the racemic mixture, the difference between enantiomers can mean a difference between therapeutic and adverse effects, as well as in beneficial pharmacological effect and potency. © 2010 The Author(s).

Binding of small molecules to DNA junctions

Previous results in our laboratory suggest that the (CG) 4 segments whether present in a right-handed or a left-handed conformation form distinctive junctions with adjacent random sequences. These junctions and their associated sequences have unique structural and thermodynamic properties that may be recognized by DNA-binding molecules. This study probes these sequences by using the following small ligands: actinomycin D, 1,4-bis(((di(aminoethyl)amino)ethyl)amino)anthracene-9,10-dione, ametantrone, and tris(phenanthroline)ruthenium (II). These ligands may recognize the distinctive features associated to the (CG)4 segment and its junctions and thus interact preferentially near these sequences. Restriction enzyme inhibition assays were used to determine whether or not binding interactions took place, and to approximate locations of these interactions. These binding studies are first carried out using two small synthetic oligomers BZ-III and BZ-IV. The (5meCG)4 segment present in BZ-III adopts the Z-conformation in the presence of 50 m M Co(NH3)63+. In BZ-IV, the unmethylated (CG)4 segment changes to a non-B conformation in the presence of 50 m M Co(NH3)63+. BZ-IV, containing the (CG)4 segment, was inserted into a clone plasmid then digested with the restriction enzyme Hinf I to produce a larger fragment that contains the (CG)4 segment. The results obtained on the small oligomers and on the larger fragment for restriction enzyme Mbo I indicate that 1,4-bis(((di(aminoethyl)amino)ethyl)amino)anthracene-9,10-dione binds more efficiently at or near the (CG)4 segment. Restriction enzymes EcoRV, Sac I and Not I with cleavage sites upstream and downstream of the (CG)4 insert were used to further localize binding interactions in the vicinity of the (CG)4 insert. RNA polymerase activity was studied in a plasmid which contained the (CG)4 insert downstream from the promoter sites of SP6 and T7 RNA polymerases. Activities of these two polymerases were studied in the presence of each one of the ligands used throughout the study. Only actinomycin D and spider, which bind at or near the (CG)4 segment, alter the activities of SP6 and T7 RNA polymerases. Surprisingly, enhancement of polymerase activity was observed in the presence of very low concentrations of actinomycin D. These results suggest that the conformational features of (CG) segments may serve in regulatory functions of DNA. ^

Correlation of throwing velocity to the results of lower-body field tests in male college baseball players

Baseball-specific athleticism, potential, and performance have been difficult to predict. Increased muscle strength and power can increase throwing velocity but the majority of research has focused on the upper body. The present study sought to determine if bilateral or unilateral lower-body field testing correlates with throwing velocity. Baseball throwing velocity scores were correlated to the following tests: medicine ball (MB) scoop toss and squat throw, bilateral and unilateral vertical jumps, single and triple broad jumps, hop and stop in both directions, lateral to medial jumps, 10- and 60-yd sprints, and both left and right single-leg 10-yd hop for speed in 42 college baseball players. A multiple regression analysis (forward method), assessing the relationship between shuffle and stretch throwing velocities and lower-body field test results determined that right-handed throwing velocity from the stretch position was most strongly predicted by lateral to medial jump right (LMJR) and body weight (BW; R = 0.322), whereas lateral to medial jump left (LMJL; R = 0.688) predicted left stretch throw. Right-handed shuffle throw was most strongly predicted by LMJR and MB scoop (R = 0.338), whereas LMJL, BW, and LMJR all contributed to left-handed shuffle throw (R = 0.982). Overall, this study found that lateral to medial jumps were consistently correlated with high throwing velocity in each of the throwing techniques, in both left-handed and right-handed throwers. This is the first study to correlate throwing velocity with a unilateral jump in the frontal plane, mimicking the action of the throwing stride.

Desordem coordenativa no desenvolvimento (DCD): Incidência em crianças do concelho de Santarém e influência na dinâmica do equilíbrio estático unipedal

As crianças que apresentam uma função motora significativamente abaixo da sua idad cronológica, com comprometimento motor, que interfere significativamente com as atividade da vida diária, o qual não esteja relacionado com uma condição médica, são diagnosticada com tendo “desordem coordenativa no desenvolvimento” (DCD) (APA, 1994). Pretendemos realizar um despiste de crianças com provável DCD e em risco de DCD nos jardin de infância do concelho de Santarém, analisar a prevalência de lateralidade, bem com analisar o padrão de equilíbrio nestas crianças. Foi empregue a banda 1 do teste MABC-2 (Movement Assessment Battery for Children-2) e método de análise de recorrência (RQA) (Riley, Balasubramaniam, & Turvey, 1999). A nossa amostra foi constituída por 239 crianças e apresentou uma percentagem de 8,4 crianças com provável DCD, mostrou que a maior incidência recaí nos rapazes, 65%. Est mesmo grupo, crianças com provável DCD, é o que apresenta maior número de sinistrómana com uma percentagem de 7,7% para os rapazes e de 28,6% nas raparigas. A criança com provável DCD, no somatório da pontuação da bateria de testes MABC-2 criança apresenta-se como provável DCD, no entanto quando foi avaliada apenas no teste d equilíbrio não manifestou problemas.

On continuous families of geometric Seifert conemanifold structures

In this paper, dedicated to Prof. Lou Kauffman, we determine the Thurston’s geometry possesed by any Seifert fibered conemanifold structure in a Seifert manifold with orbit space (Formula presented.) and no more than three exceptional fibers, whose singular set, composed by fibers, has at most three components which can include exceptional or general fibers (the total number of exceptional and singular fibers is less than or equal to three). We also give the method to obtain the holonomy of that structure. We apply these results to three families of Seifert manifolds, namely, spherical, Nil manifolds and manifolds obtained by Dehn surgery on a torus knot (Formula presented.). As a consequence we generalize to all torus knots the results obtained in [Geometric conemanifolds structures on (Formula presented.), the result of (Formula presented.) surgery in the left-handed trefoil knot (Formula presented.), J. Knot Theory Ramifications 24(12) (2015), Article ID: 1550057, 38pp., doi: 10.1142/S0218216515500571] for the case of the left handle trefoil knot. We associate a plot to each torus knot for the different geometries, in the spirit of Thurston.

Desordem coordenativa no desenvolvimento (DCD): Incidência em crianças do concelho de Santarém e influência na dinâmica do equilíbrio estático unipedal

As crianças que apresentam uma função motora significativamente abaixo da sua idad cronológica, com comprometimento motor, que interfere significativamente com as atividade da vida diária, o qual não esteja relacionado com uma condição médica, são diagnosticada com tendo “desordem coordenativa no desenvolvimento” (DCD) (APA, 1994). Pretendemos realizar um despiste de crianças com provável DCD e em risco de DCD nos jardin de infância do concelho de Santarém, analisar a prevalência de lateralidade, bem com analisar o padrão de equilíbrio nestas crianças. Foi empregue a banda 1 do teste MABC-2 (Movement Assessment Battery for Children-2) e método de análise de recorrência (RQA) (Riley, Balasubramaniam, & Turvey, 1999). A nossa amostra foi constituída por 239 crianças e apresentou uma percentagem de 8,4 crianças com provável DCD, mostrou que a maior incidência recaí nos rapazes, 65%. Est mesmo grupo, crianças com provável DCD, é o que apresenta maior número de sinistrómana com uma percentagem de 7,7% para os rapazes e de 28,6% nas raparigas. A criança com provável DCD, no somatório da pontuação da bateria de testes MABC-2 criança apresenta-se como provável DCD, no entanto quando foi avaliada apenas no teste d equilíbrio não manifestou problemas.

Caractérisation clinique et par la tomographie d’émission par positrons quantitative du trouble de l’acquisition de la coordination

Résumé : Le trouble de l’acquisition de la coordination (TAC), d’étiologie encore indéterminée, est une anomalie neurologique affectant environ 6% des enfants de l'âge scolaire. Le TAC se manifeste essentiellement par un déficit au niveau des exécutions motrices. Le présent travail de recherche comporte deux volets portant sur le TAC. Premièrement, une étude clinique sur 129 sujets âgés de 4 à 18 ans a permis de classifier les caractéristiques du TAC en sous-groupes cliniques. Trente-trois caractéristiques du TAC, les plus fréquemment rapportées dans la littérature, ont été recensées chez nos sujets. L'application d'évaluations statistiques a permis de faire ressortir trois classes essentielles. Le deuxième volet consistait à identifier les régions cérébrales impliquées dans une tâche motrice à l'aide de l'imagerie par la tomographie d'émission par positrons (TEP). Deux sujets avec TAC et deux sujets normaux ont été étudiés en deux séances d'imagerie TEP dont l'une au repos et l'autre en tapotant du pouce sur les doigts de la main gauche non-dominante. Les analyses du premier volet ont montré, entre autres, que le TAC touchait 3.17 garçons pour une fille, que tous les sujets étaient lents, que 47% des sujets étaient gauchers ou ambidextres alors que seulement 10% sont gauchers dans la population générale, que 26% avaient une dyspraxie verbale, et que 83% avaient été diagnostiqués anxieux. Les sujets ont été classés en trois sous-groupes: 1- maladroits et autres caractéristiques, sans problème de langage; 2- trouble de l’estime de soi et relation avec les pairs; 3- difficulté de langage. En imagerie, les structures cérébrales ont été classées selon leur captation du 18F-fluorodesoxyglucose (FDG) dans les hémisphères droit et gauche, avant et après l'activation, et en comparaison avec les sujets normaux. Trois types de structures cérébrales sont ressortis avec les statistiques: des structures activées, celles relativement non sollicitées et des structures désactivées. Il y avait plus de variations dans la captation du FDG chez les sujets avec TAC que chez les normaux. En conclusion, la caractérisation des sujets avec TAC par le diagnostic clinique et par l'imagerie peut procurer un plan de thérapie adéquat et ciblé étant donné que le TAC a un large spectre et pourrait coexister avec d'autres déficits cérébraux.