Construction of periodic adapted orthonormal frames on closed space curves

The construction of continuous adapted orthonormal frames along C1 closed–loop spatial curves is addressed. Such frames are important in the design of periodic spatial rigid–body motions along smooth closed paths. The construction is illustrated through the simplest non–trivial context — namely, C1 closed loops defined by a single Pythagorean–hodograph (PH) quintic space curve of a prescribed total arc length. It is shown that such curves comprise a two–parameter family, dependent on two angular variables, and they degenerate to planar curves when these parameters differ by an integer multiple of π. The desired frame is constructed through a rotation applied to the normal–plane vectors of the Euler–Rodrigues frame, so as to interpolate a given initial/final frame orientation. A general solution for periodic adapted frames of minimal twist on C1 closed–loop PH curves is possible, although this incurs transcendental terms. However, the C1 closed–loop PH quintics admit particularly simple rational periodic adapted frames

Novel role for the innate immune receptor toll-like receptor 4 (TLR4) in the regulation of the wnt signaling pathway and photoreceptor apoptosis

Recent evidence has implicated innate immunity in regulating neuronal survival in the brain during stroke and other neurodegenerations. Photoreceptors are specialized light-detecting neurons in the retina that are essential for vision. In this study, we investigated the role of the innate immunity receptor TLR4 in photoreceptors. TLR4 activation by lipopolysaccharide (LPS) significantly reduced the survival of cultured mouse photoreceptors exposed to oxidative stress. With respect to mechanism, TLR4 suppressed Wnt signaling, decreased phosphorylation and activation of the Wnt receptor LRP6, and blocked the protective effect of the Wnt3a ligand. Paradoxically, TLR4 activation prior to oxidative injury protected photoreceptors, in a phenomenon known as preconditioning. Expression of TNFα and its receptors TNFR1 and TNFR2 decreased during preconditioning, and preconditioning was mimicked by TNFα antagonists, but was independent of Wnt signaling. Therefore, TLR4 is a novel regulator of photoreceptor survival that acts through the Wnt and TNFα pathways. © 2012 Yi et al

Changed epitopes drive the antigenic drift for influenza A (H3N2) viruses

<p>Abstract</p> <p>Background</p> <p>In circulating influenza viruses, gradually accumulated mutations on the glycoprotein hemagglutinin (HA), which interacts with infectivity-neutralizing antibodies, lead to the escape of immune system (called antigenic drift). The antibody recognition is highly correlated to the conformation change on the antigenic sites (epitopes), which locate on HA surface. To quantify a changed epitope for escaping from neutralizing antibodies is the basis for the antigenic drift and vaccine development.</p> <p>Results</p> <p>We have developed an epitope-based method to identify the antigenic drift of influenza A utilizing the conformation changes on epitopes. A changed epitope, an antigenic site on HA with an accumulated conformation change to escape from neutralizing antibody, can be considered as a "key feature" for representing the antigenic drift. According to hemagglutination inhibition (HI) assays and HA/antibody complex structures, we statistically measured the conformation change of an epitope by considering the number of critical position mutations with high genetic diversity and antigenic scores. Experimental results show that two critical position mutations can induce the conformation change of an epitope to escape from the antibody recognition. Among five epitopes of HA, epitopes A and B, which are near to the receptor binding site, play a key role for neutralizing antibodies. In addition, two changed epitopes often drive the antigenic drift and can explain the selections of 24 WHO vaccine strains.</p> <p>Conclusions</p> <p>Our method is able to quantify the changed epitopes on HA for predicting the antigenic variants and providing biological insights to the vaccine updates. We believe that our method is robust and useful for studying influenza virus evolution and vaccine development.</p

Scans for signatures of selection in Russian cattle breed genomes reveal new candidate genes for environmental adaptation and acclimation

Domestication and selective breeding has resulted in over 1000 extant cattle breeds. Many of these breeds do not excel in important traits but are adapted to local environments. These adaptations are a valuable source of genetic material for efforts to improve commercial breeds. As a step toward this goal we identified candidate regions to be under selection in genomes of nine Russian native cattle breeds adapted to survive in harsh climates. After comparing our data to other breeds of European and Asian origins we found known and novel candidate genes that could potentially be related to domestication, economically important traits and environmental adaptations in cattle. The Russian cattle breed genomes contained regions under putative selection with genes that may be related to adaptations to harsh environments (e.g., AQP5, RAD50, and RETREG1). We found genomic signatures of selective sweeps near key genes related to economically important traits, such as the milk production (e.g., DGAT1, ABCG2), growth (e.g., XKR4), and reproduction (e.g., CSF2). Our data point to candidate genes which should be included in future studies attempting to identify genes to improve the extant breeds and facilitate generation of commercial breeds that fit better into the environments of Russia and other countries with similar climates

Getting more than they realized they needed: a qualitative study of women's experience of group prenatal care

<p>Abstract</p> <p>Background</p> <p>Pregnant women in Canada have traditionally received prenatal care individually from their physicians, with some women attending prenatal education classes. Group prenatal care is a departure from these practices providing a forum for women to experience medical care and child birth education simultaneously and in a group setting. Although other qualitative studies have described the experience of group prenatal care, this is the first which sought to understand the central meaning or core of the experience. The purpose of this study was to understand the central meaning of the experience of group prenatal care for women who participated in CenteringPregnancy through a maternity clinic in Calgary, Canada.</p> <p>Methods</p> <p>The study used a phenomenological approach. Twelve women participated postpartum in a one-on-one interview and/or a group validation session between June 2009 and July 2010.</p> <p>Results</p> <p>Six themes emerged: (1) "getting more in one place at one time"; (2) "feeling supported"; (3) "learning and gaining meaningful information"; (4) "not feeling alone in the experience"; (5) "connecting"; and (6) "actively participating and taking on ownership of care". These themes contributed to the core phenomenon of women "getting more than they realized they needed". The active sharing among those in the group allowed women to have both their known and subconscious needs met.</p> <p>Conclusions</p> <p>Women's experience of group prenatal care reflected strong elements of social support in that women had different types of needs met and felt supported. The findings also broadened the understanding of some aspects of social support beyond current theories. In a contemporary North American society, the results of this study indicate that women gain from group prenatal care in terms of empowerment, efficiency, social support and education in ways not routinely available through individual care. This model of care could play a key role in addressing women's needs and improving health outcomes.</p

Elongase Reactions as Control Points in Long-Chain Polyunsaturated Fatty Acid Synthesis

Extent: 9p.Background: Δ6-Desaturase (Fads2) is widely regarded as rate-limiting in the conversion of dietary α-linolenic acid (18:3n-3; ALA) to the long-chain omega-3 polyunsaturated fatty acid docosahexaenoic acid (22:6n-3; DHA). However, increasing dietary ALA or the direct Fads2 product, stearidonic acid (18:4n-3; SDA), increases tissue levels of eicosapentaenoic acid (20:5n-3; EPA) and docosapentaenoic acid (22:5n-3; DPA), but not DHA. These observations suggest that one or more control points must exist beyond ALA metabolism by Fads2. One possible control point is a second reaction involving Fads2 itself, since this enzyme catalyses desaturation of 24:5n-3 to 24:6n-3, as well as ALA to SDA. However, metabolism of EPA and DPA both require elongation reactions. This study examined the activities of two elongase enzymes as well as the second reaction of Fads2 in order to concentrate on the metabolism of EPA to DHA. Methodology/Principal Findings: The substrate selectivities, competitive substrate interactions and dose response curves of the rat elongases, Elovl2 and Elovl5 were determined after expression of the enzymes in yeast. The competitive substrate interactions for rat Fads2 were also examined. Rat Elovl2 was active with C20 and C22 polyunsaturated fatty acids and this single enzyme catalysed the sequential elongation reactions of EPA→DPA→24:5n-3. The second reaction DPA→24:5n-3 appeared to be saturated at substrate concentrations not saturating for the first reaction EPA→DPA. ALA dose-dependently inhibited Fads2 conversion of 24:5n-3 to 24:6n-3. Conclusions: The competition between ALA and 24:5n-3 for Fads2 may explain the decrease in DHA levels observed after certain intakes of dietary ALA have been exceeded. In addition, the apparent saturation of the second Elovl2 reaction, DPA→24:5n-3, provides further explanations for the accumulation of DPA when ALA, SDA or EPA is provided in the diet. This study suggests that Elovl2 will be critical in understanding if DHA synthesis can be increased by dietary means.Melissa K. Gregory, Robert A. Gibson, Rebecca J. Cook-Johnson, Leslie G. Cleland and Michael J. Jame

Normal right- and left ventricular volumes and myocardial mass in children measured by steady state free precession cardiovascular magnetic resonance

BACKGROUND: Quantification of ventricular volume by steady state free precession (SSFP) cardiovascular magnetic resonance is accurate and reproducible. Normal values exist for adults, but are lacking for children.We sought to establish normal values for left and right ventricular volumes, mass and function in healthy children by using SSFP. METHODS AND RESULTS: Fifty children (27 females, 23 males) without cardiovascular disease were evaluated. Median age was 11 years (range 7 months - 18 years), weight 35 kg (range 7-77 kg), height 146 cm (range 66-181 cm). Thirty-six examinations were performed with breath holding, 14 in freely breathing sedated children.Ventricular volumes and mass were measured in the end systolic and end diastolic phase on SSFP cine images acquired in a short axis plane as a stack of 12 contiguous slices covering full length of both ventricles. Regression analysis showed an exponential relationship between body surface area (BSA) and ventricular volumes and mass (normal value = a*BSAb). Normative curves for males and females are presented in relation to BSA for the end-diastolic volume, end-systolic volume and mass of both ventricles. Intra- and interobserver variability of the measurements was within the limits of 2% and 7% respectively, except for right ventricular mass (10%). CONCLUSION: The exponential equation for calculation of normal values for each ventricular parameter and graphical display of normative curves for data acquired in healthy children by SSFP cardiovascular magnetic resonance are provided

Circulating CD62E+ Microparticles and Cardiovascular Outcomes

BACKGROUND: Activated endothelial cells release plasma membrane submicron vesicles expressing CD62E (E-selectin) into blood, known as endothelial microparticles (EMPs). We studied whether the levels of endothelial microparticles expressing CD62E(+), CD31(+)/Annexin-V(+), or CD31(+)/CD42(-) predict cardiovascular outcomes in patients with stroke history. METHODS/PRINCIPAL FINDINGS: Patients with stroke history at least 3 months prior to enrolment were recruited. Peripheral blood EMP levels were measured by flow cytometry. Major cardiovascular events and death were monitored for 36 months. Three hundred patients were enrolled, of which 298 completed the study according to protocol. Major cardiovascular events occurred in 29 patients (9.7%). Nine patients died, five from cardiovascular causes. Cumulative event-free survival rates were lower in patients with high levels of CD62E(+) microparticles. Multivariate Cox regression analysis adjusted for cardiovascular risk factors, medications and stroke etiologic groups showed an association between a high CD62E(+) microparticle level and a risk of major cardiovascular events and hospitalization. Levels of other kinds of EMPs expressing CD31(+)/Annexin-V(+) or CD31(+)/CD42(-) markers were not predictive of cardiovascular outcomes. CONCLUSION: A high level of CD62E(+) microparticles is associated with cardiovascular events in patients with stroke history, suggesting that the systemic endothelial activation increases the risk for cardiovascular morbidities

Identification of Nicotiana tabacum Linkage Group Corresponding to the Q Chromosome Gene(s) Involved in Hybrid Lethality

BACKGROUND: A linkage map consisting of 24 linkage groups has been constructed using simple sequence repeat (SSR) markers in Nicotiana tabacum. However, chromosomal assignments of all linkage groups have not yet been made. The Q chromosome in N. tabacum encodes a gene or genes triggering hybrid lethality, a phenomenon that causes death of hybrids derived from some crosses. METHODOLOGY/PRINCIPAL FINDINGS: We identified a linkage group corresponding to the Q chromosome using an interspecific cross between an N. tabacum monosomic line lacking the Q chromosome and N. africana. N. ingulba yielded inviable hybrids after crossing with N. tabacum. SSR markers on the identified linkage group were used to analyze hybrid lethality in this cross. The results implied that one or more genes on the Q chromosome are responsible for hybrid lethality in this cross. Furthermore, the gene(s) responsible for hybrid lethality in the cross N. tabacum × N. africana appear to be on the region of the Q chromosome to which SSR markers PT30342 and PT30365 map. CONCLUSIONS/SIGNIFICANCE: Linkage group 11 corresponded to the Q chromosome. We propose a new method to correlate linkage groups with chromosomes in N. tabacum