KK6 from M2 in BLG

We study the possibility that the Kaluza-Klein monopole (KK6) world-volume action may be obtained from the multiple membranes (M2) action which is described by BLG theory. We first point out that the infinite dimensional Lie 3-algebra based on the Nambu-Poisson structure could not only provide three dimensional manifolds to allow M5 from M2, which was studied by previous authors, but also provide five dimensional manifolds to allow KK6 from M2. We next present a possible way that the U(1) field on KK6 world-volume action could be produced form the gauge potential in BLG theory.Comment: Latex, 15 pages. V3: Add theorem 2 to complete proof. V4: Detail physical interpretations and calculations in section

Delayed retinal vein recovery responses indicate both non-adaptation to stress as well as increased risk for stroke: the SABPA study

OBJECTIVES: Low or high sympatho-adrenal-medullary axis (SAM) and hypothalamic-pituitary-adrenal axis (HPA) dysregulation reflect chronic stress. Retinal vessel dynamics may relate to SAM, HPA activity and stroke risk. Our objectives were therefore to assess the relationships between retinal vessel, SAM and HPA responses, and to determine stroke risk. METHODS: A prospective bi-ethnic gender cohort (n = 275, 45 ± 9 years) was included. Urine/serum/saliva samples for SAM [norepinephrine:creatinine ratio (u-NE)] and HPA [adrenocorticotrophic hormone (ACTH), cortisol] were obtained at baseline, three-year follow up and upon flicker light-induced provocation. Diastolic ocular perfusion pressure was measured as a marker of hypo-perfusion. Retinal arterial narrowing and venous widening calibres were quantified from digital images in the mydriatic eye. A validated stress and stroke risk score was applied. RESULTS: An interaction term was fitted for venous dilation in u-NE tertiles (p ≤ 0.05) and not in u-NE median/quartiles/quintiles. Independent of race or gender, tertile 1 (low u-NE) had a 112% increase in u-NE, decreases in cortisol, and no changes in ACTH over three years (positive feedback). Tertile 3 (high u-NE) contradictorily had decreases in u-NE and cortisol, and increases in ACTH (negative feedback). In tertile 1, reduced arterial dilation, and faster arterial vasoconstriction and narrowing were related to higher SAM activity and hypo-perfusion (p ≤ 0.05), whereas delayed venous dilation, recovery and widening were related to cortisol hypo-secretion (p ≤ 0.05). In tertile 1, delayed venous recovery responses predicted stress and stroke risk [odds ratio 4.8 (1.2-19.6); p = 0.03]. These associations were not found in u-NE tertiles 2 and 3. CONCLUSIONS: In response to low norepinephrine, a reflex increase in SAM activity occurred, enhancing arterial vasoconstriction and hypo-perfusion. Concomitant HPA dysregulation attenuated retinal vein vasoactivity and tone, reflecting delayed vein recovery responses and non-adaptation to stress. These constrained vein recovery responses are indicative of increased chronic stress and stroke risk

Generic Mechanism of Emergence of Amyloid Protofilaments from Disordered Oligomeric aggregates

The presence of oligomeric aggregates, which is often observed during the process of amyloid formation, has recently attracted much attention since it has been associated with neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. We provide a description of a sequence-indepedent mechanism by which polypeptide chains aggregate by forming metastable oligomeric intermediate states prior to converting into fibrillar structures. Our results illustrate how the formation of ordered arrays of hydrogen bonds drives the formation of beta-sheets within the disordered oligomeric aggregates that form early under the effect of hydrophobic forces. Initially individual beta-sheets form with random orientations, which subsequently tend to align into protofilaments as their lengths increases. Our results suggest that amyloid aggregation represents an example of the Ostwald step rule of first order phase transitions by showing that ordered cross-beta structures emerge preferentially from disordered compact dynamical intermediate assemblies.Comment: 14 pages, 4 figure

Activity of Bdellovibrio Hit Locus Proteins, Bd0108 and Bd0109, Links Type IVa Pilus Extrusion/Retraction Status to Prey-Independent Growth Signalling

Bdellovibrio bacteriovorus are facultatively predatory bacteria that grow within gram-negative prey, using pili to invade their periplasmic niche. They also grow prey-independently on organic nutrients after undergoing a reversible switch. The nature of the growth switching mechanism has been elusive, but several independent reports suggested mutations in the hit (host-interaction) locus on the Bdellovibrio genome were associated with the transition to preyindependent growth. Pili are essential for prey entry by Bdellovibrio and sequence analysis of the hit locus predicted that it was part of a cluster of Type IVb pilus-associated genes, containing bd0108 and bd0109. In this study we have deleted the whole bd0108 gene, which is unique to Bdellovibrio, and compared its phenotype to strains containing spontaneous mutations in bd0108 and the common natural 42 bp deletion variant of bd0108. We find that deletion of the whole bd0108 gene greatly reduced the extrusion of pili, whereas the 42 bp deletion caused greater pilus extrusion than wild-type. The pili isolated from these strains were comprised of the Type IVa pilin protein; PilA. Attempts to similarly delete gene bd0109, which like bd0108 encodes a periplasmic/secreted protein, were not successful, suggesting that it is likely to be essential for Bdellovibrio viability in any growth mode. Bd0109 has a sugar binding YD- repeat motif and an N-terminus with a putative pilin-like fold and was found to interact directly with Bd0108. These results lead us to propose that the Bd0109/Bd0108 interaction regulates pilus production in Bdellovibrio (possibly by interaction with the pilus fibre at the cell wall), and that the presence (and possibly retraction state) of the pilus feeds back to alter the growth state of the Bdellovibrio cell. We further identify a novel small RNA encoded by the hit locus, the transcription of which is altered in different bd0108 mutation background

Male Microchimerism at High Levels in Peripheral Blood Mononuclear Cells from Women with End Stage Renal Disease before Kidney Transplantation

Patients with end stage renal diseases (ESRD) are generally tested for donor chimerism after kidney transplantation for tolerance mechanism purposes. But, to our knowledge, no data are available on natural and/or iatrogenic microchimerism (Mc), deriving from pregnancy and/or blood transfusion, acquired prior to transplantation. In this context, we tested the prevalence of male Mc using a real time PCR assay for DYS14, a Y-chromosome specific sequence, in peripheral blood mononuclear cells (PBMC) from 55 women with ESRD, prior to their first kidney transplantation, and compared them with results from 82 healthy women. Male Mc was also quantified in 5 native kidney biopsies obtained two to four years prior to blood testing and in PBMC from 8 women collected after female kidney transplantation, several years after the initial blood testing. Women with ESRD showed statistically higher frequencies (62%) and quantities (98 genome equivalent cells per million of host cells, gEq/M) of male Mc in their PBMC than healthy women (16% and 0.3 gEq/M, p<0.00001 and p = 0.0005 respectively). Male Mc was increased in women with ESRD whether they had or not a history of male pregnancy and/or of blood transfusion. Three out of five renal biopsies obtained a few years prior to the blood test also contained Mc, but no correlation could be established between earlier Mc in a kidney and later presence in PBMC. Finally, several years after female kidney transplantation, male Mc was totally cleared from PBMC in all women tested but one. This intriguing and striking initial result of natural and iatrogenic male Mc persistence in peripheral blood from women with ESRD raises several hypotheses for the possible role of these cells in renal diseases. Further studies are needed to elucidate mechanisms of recruitment and persistence of Mc in women with ESRD

Bivariate random-effects meta-analysis and the estimation of between-study correlation

BACKGROUND: When multiple endpoints are of interest in evidence synthesis, a multivariate meta-analysis can jointly synthesise those endpoints and utilise their correlation. A multivariate random-effects meta-analysis must incorporate and estimate the between-study correlation (ρ(B)). METHODS: In this paper we assess maximum likelihood estimation of a general normal model and a generalised model for bivariate random-effects meta-analysis (BRMA). We consider two applied examples, one involving a diagnostic marker and the other a surrogate outcome. These motivate a simulation study where estimation properties from BRMA are compared with those from two separate univariate random-effects meta-analyses (URMAs), the traditional approach. RESULTS: The normal BRMA model estimates ρ(B )as -1 in both applied examples. Analytically we show this is due to the maximum likelihood estimator sensibly truncating the between-study covariance matrix on the boundary of its parameter space. Our simulations reveal this commonly occurs when the number of studies is small or the within-study variation is relatively large; it also causes upwardly biased between-study variance estimates, which are inflated to compensate for the restriction on [Formula: see text] (B). Importantly, this does not induce any systematic bias in the pooled estimates and produces conservative standard errors and mean-square errors. Furthermore, the normal BRMA is preferable to two normal URMAs; the mean-square error and standard error of pooled estimates is generally smaller in the BRMA, especially given data missing at random. For meta-analysis of proportions we then show that a generalised BRMA model is better still. This correctly uses a binomial rather than normal distribution, and produces better estimates than the normal BRMA and also two generalised URMAs; however the model may sometimes not converge due to difficulties estimating ρ(B). CONCLUSION: A BRMA model offers numerous advantages over separate univariate synthesises; this paper highlights some of these benefits in both a normal and generalised modelling framework, and examines the estimation of between-study correlation to aid practitioners

Extracting scientific articles from a large digital archive: BioStor and the Biodiversity Heritage Library

Background: The Biodiversity Heritage Library (BHL) is a large digital archive of legacy biological literature, comprising over 31 million pages scanned from books, monographs, and journals. During the digitisation process basic metadata about the scanned items is recorded, but not article-level metadata. Given that the article is the standard unit of citation, this makes it difficult to locate cited literature in BHL. Adding the ability to easily find articles in BHL would greatly enhance the value of the archive. Description: A service was developed to locate articles in BHL based on matching article metadata to BHL metadata using approximate string matching, regular expressions, and string alignment. This article locating service is exposed as a standard OpenURL resolver on the BioStor web site http://biostor.org/openurl/. This resolver can be used on the web, or called by bibliographic tools that support OpenURL. Conclusions: BioStor provides tools for extracting, annotating, and visualising articles from the Biodiversity Heritage Library. BioStor is available from http://biostor.org

Exercise therapy for chronic low back pain:protocol for an individual participant data meta-analysis

<p>Abstract</p> <p>Background</p> <p>Low back pain (LBP) is one of the leading causes of disability and has a major socioeconomic impact. Despite a large amount of research in the field, there remains uncertainty about the best treatment approach for chronic LBP, and identification of relevant patient subgroups is an important goal. Exercise therapy is a commonly used strategy to treat chronic low back pain and is one of several interventions that evidence suggests is moderately effective.</p> <p>In parallel with an update of the 2005 Cochrane review, we will undertake an individual participant data (IPD) meta-analysis, which will allow us to standardize analyses across studies and directly derive results, and to examine differential treatment effects across individuals to estimate how patients’ characteristics modify treatment benefit.</p> <p>Methods/design</p> <p>We will use standard systematic review methods advocated by the Cochrane Collaboration to identify relevant trials. We will include trials evaluating exercise therapy compared to any or no other interventions in adult non-specific chronic LBP. Our primary outcomes of interest include pain, functional status, and return-to-work/absenteeism. We will assess potential risk of bias for each study meeting selection criteria, using criteria and methods recommended by the Cochrane BRG.</p> <p>The original individual participant data will be requested from the authors of selected trials having moderate to low risk of bias. We will test original data and compile a master dataset with information about each trial mapped on a pre-specified framework, including reported characteristics of the study sample, exercise therapy characteristics, individual patient characteristics at baseline and all follow-up periods, subgroup and treatment effect modifiers investigated. Our analyses will include descriptive, study-level meta-analysis and meta-regression analyses of the overall treatment effect, and individual-level IPD meta-analyses of treatment effect modification. IPD meta-analyses will be conducted using a one-step approach where the IPD from all studies are modeled simultaneously while accounting for the clustering of participants with studies.</p> <p>Discussion</p> <p>We will analyze IPD across a large number of LBP trials. The resulting larger sample size and consistent presentation of data will allow additional analyses to explore patient-level heterogeneity in treatment outcomes and prognosis of chronic LBP.</p