A live vaccine against Neospora caninum abortions in cattle

CommentaryMichael P. Reichel, Dadín P. Moore, Andrew Hemphill, Luis M. Ortega-Mora, J.P. Dubey, John T. Elli

A Candidate Sub-Parsec Supermassive Binary Black Hole System

We identify SDSS J153636.22+044127.0, a QSO discovered in the Sloan Digital Sky Survey, as a promising candidate for a binary black hole system. This QSO has two broad-line emission systems separated by 3500 km/sec. The redder system at z=0.3889 also has a typical set of narrow forbidden lines. The bluer system (z=0.3727) shows only broad Balmer lines and UV Fe II emission, making it highly unusual in its lack of narrow lines. A third system, which includes only unresolved absorption lines, is seen at a redshift, z=0.3878, intermediate between the two emission-line systems. While the observational signatures of binary nuclear black holes remain unclear, J1536+0441 is unique among all QSOs known in having two broad-line regions, indicative of two separate black holes presently accreting gas. The interpretation of this as a bound binary system of two black holes having masses of 10^8.9 and 10^7.3 solar masses, yields a separation of ~ 0.1 parsec and an orbital period of ~100 years. The separation implies that the two black holes are orbiting within a single narrow-line region, consistent with the characteristics of the spectrum. This object was identified as an extreme outlier of a Karhunen-Loeve Transform of 17,500 z < 0.7 QSO spectra from the SDSS. The probability of the spectrum resulting from a chance superposition of two QSOs with similar redshifts is estimated at 2X10^-7, leading to the expectation of 0.003 such objects in the sample studied; however, even in this case, the spectrum of the lower redshift QSO remains highly unusual.Comment: 8 pages, 2 figures, Nature in pres

Performance of normal young adults in two temporal resolution tests

BACKGROUND: temporal auditory processing is defined as the perception of sound or of sound alteration within a restricted time interval and is considered a fundamental ability for the auditory perception of verbal and non verbal sounds, for the perception of music, rhythm, periodicity and in the discrimination of pitch, duration and of phonemes. AIM: to compare the performance of normal Brazilian adults in two temporal resolution tests: the Gaps-in-Noise Test (GIN) and the Random Gap Detection Test (RGDT), and to analyze potential differences of performance in these two tests. METHOD: twenty-five college students with normal hearing (11 males and 14 females) and no history of educational, neurological and/or language problems, underwent the GIN and RGDT at 40dB SL. RESULTS: statistically significant gender effects for both tests were found, with female participants showing poorer performance on both temporal processing tests. In addition, a comparative analysis of the results obtained in the GIN and RGDT revealed significant differences in the threshold measures derived for these two tests. In general, significantly better gap detection thresholds were observed for both male and female participants on the GIN test when compared to the results obtained for the RGDT. CONCLUSION: male participants presented better performances on both RGDT and GIN, when compared to the females. There were no differences in performance between right and left ears on the GIN test. Participants of the present investigation, males and females, performed better on the GIN when compared to the RGDT. The GIN presented advantages over the RGDT, not only in terms of clinical validity and sensibility, but also in terms of application and scoring.TEMA: o processamento auditivo temporal se refere a percepção de um evento sonoro ou de uma alteração no mesmo, dentro de um intervalo definido de tempo e é considerado uma habilidade fundamental na percepção auditiva de sons verbais e não verbais, na percepção de música, ritmo e pontuação e na discriminação de pitch, de duração e de fonemas. OBJETIVO: realizar um estudo comparativo do desempenho de adultos jovens normais nos testes de resolução temporal, Random Gap Detection Test (RGDT) e Gaps-in-Noise (GIN) e analisar diferenças entre esses dois métodos de avaliação. MÉTODO: 25 universitários, 11 homens e 14 mulheres, com audição normal e sem histórico de alterações educacionais, neurológicas e/ou linguagem, foram submetidos ao RGDT e ao GIN, a 40dB NS. RESULTADO: observou-se diferença estatisticamente significante entre os sexos sendo que as mulheres apresentaram pior desempenho nos dois testes. No estudo comparativo dos resultados do RGDT e GIN, observaram-se diferenças significativas no desempenho da amostra. De maneira geral, os limiares de detecção de gap no teste GIN foram melhores do que os limiares obtidos no RGDT. CONCLUSÃO: o sexo masculino teve melhor desempenho tanto no teste RGDT quanto no GIN, quando comparado ao feminino. Além disso, não houve diferença significante nas repostas do GIN nas orelhas direita e esquerda. Os sujeitos deste estudo tiveram melhor desempenho no teste GIN, quando comparado ao RGDT, tanto no sexo masculino quanto no feminino. Portanto, o teste GIN apresentou vantagens sobre o RGDT não apenas quanto à sua validade e sensibilidade, mas também com relação a sua aplicação e correção dos resultados.University of Massachusetts Amherst Department of Communication DisordersUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaFaculdades Metropolitanas UnidasPurdue UniversityUniversity of Massachusetts Department of Communication DisordersUNIFESP, EPMSciEL

Decreasing intensity of open-ocean convection in the Greenland and Iceland seas

The air–sea transfer of heat and fresh water plays a critical role in the global climate system. This is particularly true for the Greenland and Iceland seas, where these fluxes drive ocean convection that contributes to Denmark Strait overflow water, the densest component of the lower limb of the Atlantic Meridional Overturning Circulation (AMOC). Here we show that the wintertime retreat of sea ice in the region, combined with different rates of warming for the atmosphere and sea surface of the Greenland and Iceland seas, has resulted in statistically significant reductions of approximately 20% in the magnitude of the winter air–sea heat fluxes since 1979. We also show that modes of climate variability other than the North Atlantic Oscillation (NAO) are required to fully characterize the regional air–sea interaction. Mixed-layer model simulations imply that further decreases in atmospheric forcing will exceed a threshold for the Greenland Sea whereby convection will become depth limited, reducing the ventilation of mid-depth waters in the Nordic seas. In the Iceland Sea, further reductions have the potential to decrease the supply of the densest overflow waters to the AMOC

Nodal dynamics, not degree distributions, determine the structural controllability of complex networks

Structural controllability has been proposed as an analytical framework for making predictions regarding the control of complex networks across myriad disciplines in the physical and life sciences (Liu et al., Nature:473(7346):167-173, 2011). Although the integration of control theory and network analysis is important, we argue that the application of the structural controllability framework to most if not all real-world networks leads to the conclusion that a single control input, applied to the power dominating set (PDS), is all that is needed for structural controllability. This result is consistent with the well-known fact that controllability and its dual observability are generic properties of systems. We argue that more important than issues of structural controllability are the questions of whether a system is almost uncontrollable, whether it is almost unobservable, and whether it possesses almost pole-zero cancellations.Comment: 1 Figures, 6 page

Cross-sectional associations between sleep duration, sedentary time, physical activity, and adiposity indicators among Canadian preschool-aged children using compositional analyses

Abstract Background Sleep duration, sedentary behaviour, and physical activity are three co-dependent behaviours that fall on the movement/non-movement intensity continuum. Compositional data analyses provide an appropriate method for analyzing the association between co-dependent movement behaviour data and health indicators. The objectives of this study were to examine: (1) the combined associations of the composition of time spent in sleep, sedentary behaviour, light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA) with adiposity indicators; and (2) the association of the time spent in sleep, sedentary behaviour, LPA, or MVPA with adiposity indicators relative to the time spent in the other behaviours in a representative sample of Canadian preschool-aged children. Methods Participants were 552 children aged 3 to 4 years from cycles 2 and 3 of the Canadian Health Measures Survey. Sedentary time, LPA, and MVPA were measured with Actical accelerometers (Philips Respironics, Bend, OR USA), and sleep duration was parental reported. Adiposity indicators included waist circumference (WC) and body mass index (BMI) z-scores based on World Health Organization growth standards. Compositional data analyses were used to examine the cross-sectional associations. Results The composition of movement behaviours was significantly associated with BMI z-scores (p = 0.006) but not with WC (p = 0.718). Further, the time spent in sleep (BMI z-score: γ sleep  = −0.72; p = 0.138; WC: γ sleep  = −1.95; p = 0.285), sedentary behaviour (BMI z-score: γ SB  = 0.19; p = 0.624; WC: γ SB  = 0.87; p = 0.614), LPA (BMI z-score: γ LPA  = 0.62; p = 0.213, WC: γ LPA  = 0.23; p = 0.902), or MVPA (BMI z-score: γ MVPA  = −0.09; p = 0.733, WC: γ MVPA  = 0.08; p = 0.288) relative to the other behaviours was not significantly associated with the adiposity indicators. Conclusions This study is the first to use compositional analyses when examining associations of co-dependent sleep duration, sedentary time, and physical activity behaviours with adiposity indicators in preschool-aged children. The overall composition of movement behaviours appears important for healthy BMI z-scores in preschool-aged children. Future research is needed to determine the optimal movement behaviour composition that should be promoted in this age group

A single residue substitution in the receptor-binding domain of H5N1 hemagglutinin is critical for packaging into pseudotyped lentiviral particles

© 2012 Tang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Serological studies for influenza infection and vaccine response often involve microneutralization and hemagglutination inhibition assays to evaluate neutralizing antibodies against human and avian influenza viruses, including H5N1. We have previously characterized lentiviral particles pseudotyped with H5-HA (H5pp) and validated an H5pp-based assay as a safe alternative for high-throughput serological studies in BSL-2 facilities. Here we show that H5-HAs from different clades do not always give rise to efficient production of H5pp and the underlying mechanisms are addressed. Methodology/Findings: We have carried out mutational analysis to delineate the molecular determinants responsible for efficient packaging of HA from A/Cambodia/40808/2005 (H5Cam) and A/Anhui/1/2005 (H5Anh) into H5pp. Our results demonstrate that a single A134V mutation in the 130-loop of the receptor binding domain is sufficient to render H5Anh the ability to generate H5Anh-pp efficiently, whereas the reverse V134A mutation greatly hampers production of H5Cam-pp. Although protein expression in total cell lysates is similar for H5Anh and H5Cam, cell surface expression of H5Cam is detected at a significantly higher level than that of H5Anh. We further demonstrate by several independent lines of evidence that the behaviour of H5Anh can be explained by a stronger binding to sialic acid receptors implicating residue 134. Conclusions: We have identified a single A134V mutation as the molecular determinant in H5-HA for efficient incorporation into H5pp envelope and delineated the underlying mechanism. The reduced binding to sialic acid receptors as a result of the A134V mutation not only exerts a critical influence in pseudotyping efficiency of H5-HA, but has also an impact at the whole virus level. Because A134V substitution has been reported as a naturally occurring mutation in human host, our results may have implications for the understanding of human host adaptation of avian influenza H5N1 virusesThis work was supported by grants from the Research Fund for the Control of Infectious Diseases of Hong Kong (RFCID#08070972), the Area of Excellence Scheme of the University Grants Committee (grant AoE/M-12/-06 of the Hong Kong Special Administrative Region, China), the French Ministry of Health, and the RESPARI project of the Institut Pasteur International Network

An integrated general practice and pharmacy-based intervention to promote the use of appropriate preventive medications among individuals at high cardiovascular disease risk: protocol for a cluster randomized controlled trial

Background: Cardiovascular diseases (CVD) are responsible for significant morbidity, premature mortality, and economic burden. Despite established evidence that supports the use of preventive medications among patients at high CVD risk, treatment gaps remain. Building on prior evidence and a theoretical framework, a complex intervention has been designed to address these gaps among high-risk, under-treated patients in the Australian primary care setting. This intervention comprises a general practice quality improvement tool incorporating clinical decision support and audit/feedback capabilities; availability of a range of CVD polypills (fixed-dose combinations of two blood pressure lowering agents, a statin ± aspirin) for prescription when appropriate; and access to a pharmacy-based program to support long-term medication adherence and lifestyle modification. Methods: Following a systematic development process, the intervention will be evaluated in a pragmatic cluster randomized controlled trial including 70 general practices for a median period of 18 months. The 35 general practices in the intervention group will work with a nominated partner pharmacy, whereas those in the control group will provide usual care without access to the intervention tools. The primary outcome is the proportion of patients at high CVD risk who were inadequately treated at baseline who achieve target blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) levels at the study end. The outcomes will be analyzed using data from electronic medical records, utilizing a validated extraction tool. Detailed process and economic evaluations will also be performed. Discussion: The study intends to establish evidence about an intervention that combines technological innovation with team collaboration between patients, pharmacists, and general practitioners (GPs) for CVD prevention. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN1261600023342

Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B

Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells. Application of PKA inhibitors, KT5720 or H89, caused a significant inhibition of Kv currents. Tonic PKA-mediated activation of Kv appears maximal as application of isoprenaline (a β-adrenoceptor agonist) or dibutyryl-cAMP failed to enhance Kv currents. We also show that this modulation of Kv by PKA can be reversed by protein phosphatase 2B/calcineurin (PP2B). PKA-dependent inhibition of Kv by KT5720 can be abrogated by pre-treatment with the PP2B inhibitor cyclosporin A, or inclusion of a PP2B auto-inhibitory peptide in the pipette solution. Finally, we demonstrate that tonic PKA-mediated modulation of Kv requires intact caveolae. Pre-treatment of the cells with methyl-β-cyclodextrin to deplete cellular cholesterol, or adding caveolin-scaffolding domain peptide to the pipette solution to disrupt caveolae-dependent signalling each attenuated PKA-mediated modulation of the Kv current. These findings highlight a novel, caveolae-dependent, tonic modulatory role of PKA on Kv channels providing new insight into mechanisms and the potential for pharmacological manipulation of vascular tone