409 research outputs found
A canine BCAN microdeletion associated with episodic falling syndrome
Episodic falling syndrome (EFS) is a canine paroxysmal hypertonicity disorder found in Cavalier King Charles spaniels. Episodes are triggered by exercise, stress or excitement and characterized by progressive hypertonicity throughout the thoracic and pelvic limbs, resulting in a characteristic 'deer-stalking' position and/or collapse. We used a genome-wide association strategy to map the EFS locus to a 3.48 Mb critical interval on canine chromosome 7. By prioritizing candidate genes on the basis of biological plausibility, we found that a 15.7 kb deletion in BCAN, encoding the brain-specific extracellular matrix proteoglycan brevican, is associated with EFS. This represents a compelling causal mutation for EFS, since brevican has an essential role in the formation of perineuronal nets governing synapse stability and nerve conduction velocity. Mapping of the deletion breakpoint enabled the development of Multiplex PCR and Multiplex Ligation-dependent Probe Amplification (MLPA) genotyping tests that can accurately distinguish normal, carrier and affected animals. Wider testing of a larger population of CKCS dogs without a history of EFS from the USA revealed that carriers are extremely common (12.9%). The development of molecular genetic tests for the EFS microdeletion will allow the implementation of directed breeding programs aimed at minimizing the number of animals with EFS and enable confirmatory diagnosis and pharmacotherapy of affected dogs
Constraints and prospects for contraceptive service provision to young people in Uganda: providers' perspectives
<p>Abstract</p> <p>Background</p> <p>Unintended pregnancies lead to unsafe abortions, which are a leading cause of preventable maternal mortality among young women in Uganda. There is a discrepancy between the desire to prevent pregnancy and actual contraceptive use. Health care providers' perspectives on factors influencing contraceptive use and service provision to young people aged 15-24 in two rural districts in Uganda were explored.</p> <p>Methods</p> <p>Semi-structured questionnaires were used for face- to-face interviews with 102 providers of contraceptive service at public, private not-for-profit, and private for-profit health facilities in two rural districts in Uganda. Descriptive and inferential statistics were used in the analysis of data.</p> <p>Results</p> <p>Providers identified service delivery, provider-focused, structural, and client-specific factors that influence contraceptive use among young people. Contraceptive use and provision to young people were constrained by sporadic contraceptive stocks, poor service organization, and the limited number of trained personnel, high costs, and unfriendly service. Most providers were not competent enough to provide long-acting methods. There were significant differences in providers' self-rated competence by facility type; private for-profit providers' competence was limited for most contraceptives. Providers had misconceptions about contraceptives, they had negative attitudes towards the provision of contraceptives to young people, and they imposed non-evidence-based age restrictions and consent requirements. Thus, most providers were not prepared or were hesitant to give young people contraceptives. Short-acting methods were, however, considered acceptable for young married women and those with children.</p> <p>Conclusion</p> <p>Provider, client, and health system factors restricted contraceptive provision and use for young people. Their contraceptive use prospects are dependent on provider behavior and health system improvements.</p
Massive Spin-2 States as the Origin of the Top Quark Forward-Backward Asymmetry
We show that the anomalously large top quark forward-backward asymmetry
observed by CDF and D\O\, can naturally be accommodated in models with
flavor-violating couplings of a new massive spin-2 state to quarks. Regardless
of its origin, the lowest-order couplings of a spin-2 boson to fermions are
analogous to the coupling of the graviton to energy/momentum, leading to strong
sensitivity of the effects associated with its virtual exchange to the energy
scales at hand. Precisely due to this fact, the observed dependence of the
asymmetry on the invariant mass fits nicely into the proposed
framework. In particular, we find a vast parameter space which can lead to the
central value for the observed forward-backward asymmetry in the high mass bin,
while being in accord with all of the existing experimental constraints.Comment: added discussion of differential observables at the LHC, matches
version accepted for publication in JHE
Top quark forward-backward asymmetry in R-parity violating supersymmetry
The interaction of bottom squark-mediated top quark pair production,
occurring in the R-parity violating minimal supersymmetric standard model
(MSSM), is proposed as an explanation of the anomalously large
forward-backward asymmetry (FBA) observed at the Tevatron. We find that this
model can give a good fit to top quark data, both the inclusive and invariant
mass-dependent asymmetries, while remaining consistent (at the 2-
level) with the total and differential production cross-sections. The scenario
is challenged by strong constraints from atomic parity violation (APV), but we
point out an extra diagram for the effective down quark-Z vertex, involving the
same coupling constant as required for the FBA, which tends to weaken the APV
constraint, and which can nullify it for reasonable values of the top squark
masses and mixing angle. Large contributions to flavor-changing neutral
currents can be avoided if only the third generation of sparticles is light.Comment: 24 pages, 7 figures. v3: included LHC top production cross section
data; model still consistent at 2 sigma leve
Structure in 6D and 4D N=1 supergravity theories from F-theory
We explore some aspects of 4D supergravity theories and F-theory vacua that
are parallel to structures in the space of 6D theories. The spectrum and
topological terms in 4D supergravity theories correspond to topological data of
F-theory geometry, just as in six dimensions. In particular, topological
axion-curvature squared couplings appear in 4D theories; these couplings are
characterized by vectors in the dual to the lattice of axion shift symmetries
associated with string charges. These terms are analogous to the Green-Schwarz
terms of 6D supergravity theories, though in 4D the terms are not generally
linked with anomalies. We outline the correspondence between F-theory topology
and data of the corresponding 4D supergravity theories. The correspondence of
geometry with structure in the low-energy action illuminates topological
aspects of heterotic-F-theory duality in 4D as well as in 6D. The existence of
an F-theory realization also places geometrical constraints on the 4D
supergravity theory in the large-volume limit.Comment: 63 page
Supporting families in the context of adult traumatic brain injury
Families are fundamental to the wellbeing, quality of life and functional and social outcomes of individuals who sustain traumatic brain injury (TBI). However, the family is often vulnerable and at risk from the challenge of supporting an individual who has been left with long-term neurological disability. Considering the young population often affected, the resulting conditions can have significant emotional and financial burden for families and service providing for their long-term needs. The National Service Framework for Long-term Conditions acknowledges that the whole family is affected by neurological disability and it suggests that a 'whole-family' approach to managing TBI may be useful. This paper will argue that both family systems theory and family-centred care are frameworks that may be helpful in achieving the 'whole-family' approach in practice. However, future research is needed that will assess the efficacy of these and other approaches so that health-care services know the true value of any such intervention.N/
Cross-sectional interactions between quality of the physical and social environment and self-reported physical activity in adults living in income-deprived communities
Background: Understanding the environmental determinants of physical activity in populations at high risk of inactivity could contribute to the development of effective interventions. Socioecological models of activity propose that environmental factors have independent and interactive effects of physical activity but there is a lack of research into interactive effects.
Objectives:
This study aimed to explore independent and interactive effects of social and physical environmental factors on self-reported physical activity in income-deprived communities.
Methods:
Participants were 5,923 adults in Glasgow, United Kingdom. Features of the social environment were self-reported. Quality of the physical environment was objectively-measured. Neighbourhood walking and participation in moderate physical activity [MPA] on â„5 days/week was self-reported. Multilevel multivariate logistic regression models tested independent and interactive effects of environmental factors on activity.
Results:
âSocial supportâ (walking: OR:1.22,95%CI=1.06-1.41,p<0.01; MPA: OR:0.79,95%CI=0.67-0.94,p<0.01), âsocial interactionâ (walking: OR:1.25,95%CI=1.10-1.42,p<0.01; MPA: OR:6.16,95%CI=5.14-7.37,p<0.001) and âcohesion and safetyâ (walking: OR:1.78,95%CI=1.56-2.03,p<0.001; MPA: OR:1.93,95%CI=1.65-2.27,p<0.001), but not âtrust and empowermentâ, had independent effects on physical activity. âAesthetics of built formâ (OR:1.47,95%CI=1.22-1.77,p<0.001) and âaesthetics and maintenance of open spaceâ (OR:1.32, 95%CI=1.13-1.54,p<0.01) were related to walking. âPhysical disorderâ (OR:1.63,95%CI=1.31-2.03,p<0.001) had an independent effect on MPA. Interactive effects of social and physical factors on walking and MPA were revealed.
Conclusions:
Findings suggest that intervening to create activity-supportive environments in deprived communities may be most effective when simultaneously targeting the social and physical neighbourhood environment
Prediction of HIV-1 virus-host protein interactions using virus and host sequence motifs
<p>Abstract</p> <p>Background</p> <p>Host protein-protein interaction networks are altered by invading virus proteins, which create new interactions, and modify or destroy others. The resulting network topology favors excessive amounts of virus production in a stressed host cell network. Short linear peptide motifs common to both virus and host provide the basis for host network modification.</p> <p>Methods</p> <p>We focused our host-pathogen study on the binding and competing interactions of HIV-1 and human proteins. We showed that peptide motifs conserved across 70% of HIV-1 subtype B and C samples occurred in similar positions on HIV-1 proteins, and we documented protein domains that interact with these conserved motifs. We predicted which human proteins may be targeted by HIV-1 by taking pairs of human proteins that may interact via a motif conserved in HIV-1 and the corresponding interacting protein domain.</p> <p>Results</p> <p>Our predictions were enriched with host proteins known to interact with HIV-1 proteins ENV, NEF, and TAT (p-value < 4.26E-21). Cellular pathways statistically enriched for our predictions include the T cell receptor signaling, natural killer cell mediated cytotoxicity, cell cycle, and apoptosis pathways. Gene Ontology molecular function level 5 categories enriched with both predicted and confirmed HIV-1 targeted proteins included categories associated with phosphorylation events and adenyl ribonucleotide binding.</p> <p>Conclusion</p> <p>A list of host proteins highly enriched with those targeted by HIV-1 proteins can be obtained by searching for host protein motifs along virus protein sequences. The resulting set of host proteins predicted to be targeted by virus proteins will become more accurate with better annotations of motifs and domains. Nevertheless, our study validates the role of linear binding motifs shared by virus and host proteins as an important part of the crosstalk between virus and host.</p
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