DivIVA controls progeny morphology and diverse ParA proteins regulate cell division or gliding motility in Bdellovibrio bacteriovorus

The predatory bacterium B. bacteriovorus grows and divides inside the periplasm of Gram-negative bacteria, forming a structure known as a bdelloplast. Cell division of predators inside the dead prey cell is not by binary fission but instead by synchronous division of a single elongated filamentous cell into odd or even numbers of progeny cells. Bdellovibrio replication and cell division processes are dependent on the finite level of nutrients available from inside the prey bacterium. The filamentous growth and division process of the predator maximizes the number of progeny produced by the finite nutrients in a way that binary fission could not. To learn more about such an unusual growth profile, we studied the role of DivIVA in the growing Bdellovibrio cell. This protein is well known for its link to polar cell growth and spore formation in Gram-positive bacteria, but little is known about its function in a predatory growth context. We show that DivIVA is expressed in the growing B. bacteriovorus cell and controls cell morphology during filamentous cell division, but not the number of progeny produced. Bacterial Two Hybrid (BTH) analysis shows DivIVA may interact with proteins that respond to metabolic indicators of amino-acid biosynthesis or changes in redox state. Such changes may be relevant signals to the predator, indicating the consumption of prey nutrients within the sealed bdelloplast environment. ParA, a chromosome segregation protein, also contributes to bacterial septation in many species. The B. bacteriovorus genome contains three ParA homologs; we identify a canonical ParAB pair required for predatory cell division and show a BTH interaction between a gene product encoded from the same operon as DivIVA with the canonical ParA. The remaining ParA proteins are both expressed in Bdellovibrio but are not required for predator cell division. Instead, one of these ParA proteins coordinates gliding motility, changing the frequency at which the cells reverse direction. Our work will prime further studies into how one bacterium can co-ordinate its cell division with the destruction of another bacterium that it dwells within

Current induced switching of magnetic domains to a perpendicular configuration

In a ferromagnet--normal-metal--ferromagnet trilayer, a current flowing perpendicularly to the layers creates a torque on the magnetic moments of the ferromagnets. When one of the contacts is superconducting, the torque not only favors parallel or antiparallel alignment of the magnetic moments, as is the case for two normal contacts, but can also favor a configuration where the two moments are perpendicular. In addition, whereas the conductance for parallel and antiparallel magnetic moments is the same, signalling the absence of giant magnetoresistance in the usual sense, the conductance is greater in the perpendicular configuration. Thus, a negative magnetoconductance is predicted, in contrast with the usual giant magnetoresistance.Comment: 4 pages, 3 figures, major rewriting of the technical par

Determination of the linear frequency response of single pipelines using persistent transient excitation: a numerical investigation

The linear frequency response of a fluid-filled pipeline extracted by fluid transient waves can be used to detect leaks in pipelines. This research conducts numerical analysis on how to accurately determine the linear frequency response diagram (FRD) of single pipelines using persistent transient pressure signals. Two types of persistent signals, the maximum-length binary sequence and the inverse-repeat sequence (IRS), are compared in terms of the accuracy in estimating the linear response of a pipeline at resonant frequencies. The IRS is found to be more appropriate for identifying the linear portion of the FRD of a pipeline, since its antisymmetric property can supress part of the nonlinear response. Numerical simulations are conducted to verify the findings. © 2013 © 2013 International Association for Hydro-Environment Engineering and Research.Jinzhe Gong, Angus R. Simpson, Martin F. Lambert & Aaron C. Zecchi

A possible rheological model of gum candies

An appropriate rheological model can be used in production of good quality gum candy required by consumers. For this purpose Creep-Recovery Test (CRT) curves were recorded with a Stable Micro System TA.XT-2 precision texture analyser with 75 mm diameter cylinder probe on gum candies purchased from the local market. The deformation speed was 0.2 mm s−1, the creeping- and recovering time was 60 s, while the loading force was set to 1 N, 2 N, 5 N, 7 N, and 10 N. The two-element Kelvin-Voigt-model, a three-element model, and the four-element Burgers-model were fitted on the recorded creep data, and then the parameters of the models were evaluated. The best fitting from the used models was given by the Burgers model

Novel GCH1 variant in Dopa-responsive dystonia and Parkinson's disease

Background: GTP cyclohydrolase I (GCH1) mutations are the commonest cause of Dopa-responsive dystonia (DRD). Clinical phenotypes can be broad, even within a single family. Methods: We present clinical, genetic and functional imaging data on a British kindred in which affected subjects display phenotypes ranging from DRD to Parkinson's disease (PD). Twelve family members were studied. Clinical examination, dopamine transporter (DAT) imaging, and molecular genetic analysis of GCH1 and the commonest known familial PD-related genes were performed. Results: We have identified a novel missense variant, c.5A>G, p.(Glu2Gly), within the GCH1 gene in affected family members displaying a range of phenotypes. Two affected subjects carrying this variant had abnormal DAT imaging. These two with abnormal DAT imaging had a PD phenotype, while the remaining three subjects with the novel GCH1 variant had normal DAT imaging and a DRD phenotype. Conclusions: We propose that this GCH1 variant is pathogenic in this family and these findings suggest that similar mechanisms involving abnormal GTP cyclohydolase I may underlie both PD and DRD. GCH1 genetic testing should be considered in patients with PD and a family history of DRD

Vortices, Instantons and Branes

The purpose of this paper is to describe a relationship between the moduli space of vortices and the moduli space of instantons. We study charge k vortices in U(N) Yang-Mills-Higgs theories and show that the moduli space is isomorphic to a special Lagrangian submanifold of the moduli space of k instantons in non-commutative U(N) Yang-Mills theories. This submanifold is the fixed point set of a U(1) action on the instanton moduli space which rotates the instantons in a plane. To derive this relationship, we present a D-brane construction in which the dynamics of vortices is described by the Higgs branch of a U(k) gauge theory with 4 supercharges which is a truncation of the familiar ADHM gauge theory. We further describe a moduli space construction for semi-local vortices, lumps in the CP(N) and Grassmannian sigma-models, and vortices on the non-commutative plane. We argue that this relationship between vortices and instantons underlies many of the quantitative similarities shared by quantum field theories in two and four dimensions.Comment: 32 Pages, 4 Figure

Analysis of rare variants in the C3 gene in patients with age-related macular degeneration

Age-related macular degeneration (AMD) is a progressive retinal disorder affecting over 33 million people worldwide. Genome-wide association studies (GWASs) for AMD identified common variants at 19 loci accounting for 15-65% of the heritability and it has been hypothesized that the missing heritability may be attributed to rare variants with large effect sizes. Common variants in the complement component 3 (C3) gene have been associated with AMD and recently a rare C3 variant (Lys155Gln) was identified which exerts a large effect on AMD susceptibility independent of the common variants. To explore whether additional rare variants in the C3 gene are associated with AMD, we sequenced all coding exons in 84 unrelated AMD cases. Subsequently, we genotyped all identified variants in 1474 AMD cases and 2258 controls. Additionally, because of the known genetic overlap between AMD and atypical hemolytic uremic syndrome (aHUS), we genotyped two recurrent aHUS-associated C3 mutations in the entire cohort. Overall, we identified three rare variants (Lys65Gln (P = 0.04), Arg735Trp (OR = 17.4, 95% CI = 2.2-136; P = 0.0003), and Ser1619Arg (OR = 5.2, 95% CI = 1.0-25; P = 0.05) at the C3 locus that are associated with AMD in our EUGENDA cohort. However, the Arg735Trp and Ser1619Arg variants were not found to be associated with AMD in the Rotterdam Study. The Lys65Gln variant was only identified in patients from Nijmegen, the Netherlands, and thus may represent a region-specific AMD risk variant

Serological and genetic complement alterations in infection-induced and complement-mediated hemolytic uremic syndrome

Background: The role of complement in the atypical form of hemolytic uremic syndrome (aHUS) has been investigated extensively in recent years. As the HUS-associated bacteria Shiga-toxin-producing Escherichia coli (STEC) can evade the complement system, we hypothesized that complement dysregulation is also important in infection-induced HUS. Methods: Serological profiles (C3, FH, FI, AP activity, C3d, C3bBbP, C3b/c, TCC, αFH) and genetic profiles (CFH, CFI, CD46, CFB, C3) of the alternative complement pathway were prospectively determined in the acute and convalescent phase of disease in children newly diagnosed with STEC-HUS or aHUS. Serological profiles were compared with those of 90 age-matched controls. Results: Thirty-seven patients were studied (26 STEC-HUS, 11 aHUS). In 39 % of them, including 28 % of STEC-HUS patients, we identified a genetic and/or acquired complement abnormality. In all patient groups, the levels of investigated alternative pathway (AP) activation markers were elevated in the acute phase and normalized in remission. The levels were significantly higher in aHUS than in STEC-HUS patients. Conclusions: In both infection-induced HUS and aHUS patients, complement is activated in the acute phase of the disease but not during remission. The C3d/C3 ratio displayed the best discrepancy between acute and convalescent phase and between STEC-HUS and aHUS and might therefore be used as a biomarker in disease diagnosis and monitoring. The presence of aberrations in the alternative complement pathway in STEC-HUS patients was remarkable, as well

High performance liquid chromatography tandem mass spectrometry dual extraction method for identification of green tea catechin metabolites excreted in human urine

The simultaneous analysis of free-form and conjugated flavonoids in the same sample is difficult but necessary to properly estimate their bioavailability. A method was developed to optimise the extraction of both free and conjugated forms of catechins and metabolites in a biological sample following the consumption of green tea. A double-blind randomised controlled trial was performed in which 26 volunteers consumed daily green tea and vitamin C supplements and 24 consumed a placebo for 3 months. Urine was collected for 24h at 4 separate time points (pre- and post-consumption) to confirm compliance to the supplementation and to distinguish between placebo and supplementation consumption. The urine was assessed for both free and conjugated metabolites of green tea using LC-MS2 analysis, after a combination extraction method, which involved an ethyl acetate extraction followed by an acetonitrile protein precipitation. The combination method resulted in a good recovery of EC-O-sulphate (91±7%), EGC-O-glucuronide (94±6%), EC (95±6%), EGC (111±5%) and ethyl gallate (74±3%). A potential total of 55 catechin metabolites were investigated, and of these, 26 conjugated (with methyl, glucuronide or sulphate groups) and 3 free-form (unconjugated) compounds were identified in urine following green tea consumption. The majority of EC and EGC conjugates significantly increased post-consumption of green tea in comparison to baseline (pre-supplementation) samples. The conjugated metabolites associated with the highest peak areas were O-methyl-EC-O-sulphate and the valerolactones M6/M6'-O-sulphate. In line with previous studies, EC and EGC were only identified as conjugated derivatives, and EGCG and ECG were not found as mono-conjugated or free-forms. In summary, the method reported here provides a good recovery of catechin compounds and is appropriate for use in the assessment of flavonoid bioavailability, particularly for biological tissues that may contain endogenous deconjugating enzymes