73 research outputs found

    Approximation for Cooperative Interactions of a Spatially-Detailed Cardiac Sarcomere Model

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    We developed a novel ordinary differential equation (ODE) model, which produced results that correlated well with the Monte Carlo (MC) simulation when applied to a spatially-detailed model of the cardiac sarcomere. Configuration of the novel ODE model was based on the Ising model of myofilaments, with the “co-operative activation” effect introduced to incorporate nearest-neighbor interactions. First, a set of parameters was estimated using arbitrary Ca transient data to reproduce the combinational probability for the states of three consecutive regulatory units, using single unit probabilities for central and neighboring units in the MC simulation. The parameter set thus obtained enabled the calculation of the state transition of each unit using the ODE model with reference to the neighboring states. The present ODE model not only provided good agreement with the MC simulation results but was also capable of reproducing a wide range of experimental results under both steady-state and dynamic conditions including shortening twitch. The simulation results suggested that the nearest-neighbor interaction is a reasonable approximation of the cooperativity based on end-to-end interactions. Utilizing the modified ODE model resulted in a reduction in computational costs but maintained spatial integrity and co-operative effects, making it a powerful tool in cardiac modeling

    Evolution of infectious bronchitis virus in the field after homologous vaccination introduction

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    International audienceAbstractDespite the fact that vaccine resistance has been typically considered a rare phenomenon, some episodes of vaccine failure have been reported with increasing frequency in intensively-raised livestock. Infectious bronchitis virus (IBV) is a widespread avian coronavirus, whose control relies mainly on extensive vaccine administration. Unfortunately, the continuous emergence of new vaccine-immunity escaping variants prompts the development of new vaccines. In the present work, a molecular epidemiology study was performed to evaluate the potential role of homologous vaccination in driving IBV evolution. This was undertaken by assessing IBV viral RNA sequences from the ORF encoding the S1 portion of viral surface glycoprotein (S) before and after the introduction of a new live vaccine on broiler farms in northern-Italy. The results of several biostatistics analyses consistently demonstrate the presence of a higher pressure in the post-vaccination period. Natural selection was detected essentially on sites located on the protein surface, within or nearby domains involved in viral attachment or related functions. This evidence strongly supports the action of vaccine-induced immunity in conditioning viral evolution, potentially leading to the emergence of new vaccine-escape variants. The great plasticity of rapidly-evolving RNA-viruses in response to human intervention, which extends beyond the poultry industry, is demonstrated, claiming further attention due to their relevance for animal and especially human health

    Genetic Modulation of Rpd3 Expression Impairs Long-Term Courtship Memory in Drosophila

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    There is increasing evidence that regulation of local chromatin structure is a critical mechanism underlying the consolidation of long-term memory (LTM), however considerably less is understood about the specific mechanisms by which these epigenetic effects are mediated. Furthermore, the importance of histone acetylation in Drosophila memory has not been reported. The histone deacetylase (HDAC) Rpd3 is abundant in the adult fly brain, suggesting a post-mitotic function. Here, we investigated the role of Rpd3 in long-term courtship memory in Drosophila. We found that while modulation of Rpd3 levels predominantly in the adult mushroom body had no observed impact on immediate recall or one-hour memory, 24-hour LTM was severely impaired. Surprisingly, both overexpression as well as RNAi-mediated knockdown of Rpd3 resulted in impairment of long-term courtship memory, suggesting that the dose of Rpd3 is critical for normal LTM

    Acceptability of a theory-based sedentary behaviour reduction intervention for older adults ('On Your Feet to Earn Your Seat').

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    Background: Adults aged 60 years and over spend most time sedentary and are the least physically active of all age groups. This early-phase study explored acceptability of a theory-based intervention to reduce sitting time and increase activity in older adults, as part of the intervention development process. Methods: An 8-week uncontrolled trial was run among two independent samples of UK adults aged 60–75 years. Sample 1, recruited from sheltered housing on the assumption that they were sedentary and insufficiently active, participated between December 2013 and March 2014. Sample 2, recruited through community and faith centres and a newsletter, on the basis of self-reported inactivity (<150 weekly minutes of moderate-to-vigorous activity) and sedentary behaviour (≥6 h mean daily sitting), participated between March and August 2014. Participants received a booklet offering 16 tips for displacing sitting with light-intensity activity and forming activity habits, and self-monitoring ‘tick-sheets’. At baseline, 4-week, and 8-week follow-ups, quantitative measures were taken of physical activity, sedentary behaviour, and habit. At 8 weeks, tick-sheets were collected and a semi-structured interview conducted. Acceptability was assessed for each sample separately, through attrition and adherence to tips, ANOVAs for behaviour and habit changes, and, for both samples combined, thematic analysis of interviews. Results: In Sample 1, 12 of 16 intervention recipients completed the study (25 % attrition), mean adherence was 40 % (per-tip range: 15–61 %), and there were no clear patterns of changes in sedentary or physical activity behaviour or habit. In Sample 2, 23 of 27 intervention recipients completed (15 % attrition), and mean adherence was 58 % (per-tip range: 39–82 %). Sample 2 decreased mean sitting time and sitting habit, and increased walking, moderate activity, and activity habit. Qualitative data indicated that both samples viewed the intervention positively, found the tips easy to follow, and reported health and wellbeing gains. Conclusions: Low attrition, moderate adherence, and favourability in both samples, and positive changes in Sample 2, indicate the intervention was acceptable. Higher attrition, lower adherence, and no apparent behavioural impact among Sample 1 could perhaps be attributable to seasonal influences. The intervention has been refined to address emergent acceptability problems. An exploratory controlled trial is underway

    Behavioral genetics and taste

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    This review focuses on behavioral genetic studies of sweet, umami, bitter and salt taste responses in mammals. Studies involving mouse inbred strain comparisons and genetic analyses, and their impact on elucidation of taste receptors and transduction mechanisms are discussed. Finally, the effect of genetic variation in taste responsiveness on complex traits such as drug intake is considered. Recent advances in development of genomic resources make behavioral genetics a powerful approach for understanding mechanisms of taste

    К проблеме социальной эффективности инноваций в профессиональном образовании

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    Movile Cave, Romania, is an unusual underground ecosystem that has been sealed off from the outside world for several million years and is sustained by non-phototrophic carbon fixation. Methane and sulfur-oxidising bacteria are the main primary producers, supporting a complex food web that includes bacteria, fungi and cave-adapted invertebrates. A range of methylotrophic bacteria in Movile Cave grow on one-carbon compounds including methylated amines, which are produced via decomposition of organic-rich microbial mats. The role of methylated amines as a carbon and nitrogen source for bacteria in Movile Cave was investigated using a combination of cultivation studies and DNA stable isotope probing (DNA-SIP) using 13C-monomethylamine (MMA). Two newly developed primer sets targeting the gene for gamma-glutamylmethylamide synthetase (gmaS), the first enzyme of the recently-discovered indirect MMA-oxidation pathway, were applied in functional gene probing. SIP experiments revealed that the obligate methylotroph Methylotenera mobilis is one of the dominant MMA utilisers in the cave. DNA-SIP experiments also showed that a new facultative methylotroph isolated in this study, Catellibacterium sp. LW-1 is probably one of the most active MMA utilisers in Movile Cave. Methylated amines were also used as a nitrogen source by a wide range of non-methylotrophic bacteria in Movile Cave. PCR-based screening of bacterial isolates suggested that the indirect MMA-oxidation pathway involving GMA and N-methylglutamate is widespread among both methylotrophic and non-methylotrophic MMA utilisers from the cave
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