Slowly cycling Rho kinase-dependent actomyosin cross-bridge slippage explains intrinsic high compliance of detrusor smooth muscle

Biological soft tissues are viscoelastic because they display timeindependent pseudoelasticity and time-dependent viscosity. However, there is evidence that the bladder may also display plasticity, defined as an increase in strain that is unrecoverable unless work is done by the muscle. In the present study, an electronic lever was used to induce controlled changes in stress and strain to determine whether rabbit detrusor smooth muscle (rDSM) is best described as viscoelastic or viscoelastic plastic. Using sequential ramp loading and unloading cycles, stress-strain and stiffness-stress analyses revealed that rDSM displayed reversible viscoelasticity, and that the viscous component was responsible for establishing a high stiffness at low stresses that increased only modestly with increasing stress compared with the large increase produced when the viscosity was absent and only pseudoelasticity governed tissue behavior. The study also revealed that rDSM underwent softening correlating with plastic deformation and creep that was reversed slowly when tissues were incubated in a Ca2+ -containing solution. Together, the data support a model of DSM as a viscoelastic-plastic material, with the plasticity resulting from motor protein activation. This model explains the mechanism of intrinsic bladder compliance as slipping cross bridges, predicts that wall tension is dependent not only on vesicle pressure and radius but also on actomyosin cross-bridge activity, and identifies a novel molecular target for compliance regulation, both physiologically and therapeutically

Successful nesting by 2 endangered Hawaiian waterbird species in a restored Indigenous wetland agroecosystem

The Hawaiian Stilt (Himantopus mexicanus knudseni) and Hawaiian Gallinule (Gallinula galeata sandvicensis) are federally endangered waterbirds endemic to the Hawaiian Islands. Both species are conservation-reliant; their population persistence is dependent on invasive predator control and removal of invasive plants that degrade habitat. We present observations of successful nesting by one Hawaiian Stilt pair and one Hawaiian Gallinule pair at a site managed within an adaptive Indigenous agroecological framework on the island of O‘ahu, Hawai‘i. The Hawaiian Stilt nest, found in February 2019, contained 4 eggs and produced 3 hatchlings, 2 of which were banded and monitored after hatching. The Hawaiian Gallinule nest, found in February 2020, contained 6 eggs and produced 5 hatchlings. Although no individuals were banded from this nest, 2 adults and 2 hatchlings were continuously observed in the nesting area after the eggs hatched. Lo‘i kalo Hawaiian wetland agroecosystems centered around the cultivation of kalo (taro; Colocasia esculenta), have the potential to expand Hawaiian waterbird habitat beyond state and federal protected areas. We are aware of unpublished accounts of Hawaiian waterbirds nesting in commercially farmed lo‘i kalo, but until now, there have been no previously published accounts of native waterbirds breeding in lo‘i kalo managed as Indigenous agroecosystems

Scientific questions for the exploration of the terrestrial planets and Jupiter - Advanced planetary missions technology program Progress report

Scientific questions and experimental design for planetary exploration of Jupiter, Mars, Mercury, and Venu

Efficient Parallel Statistical Model Checking of Biochemical Networks

We consider the problem of verifying stochastic models of biochemical networks against behavioral properties expressed in temporal logic terms. Exact probabilistic verification approaches such as, for example, CSL/PCTL model checking, are undermined by a huge computational demand which rule them out for most real case studies. Less demanding approaches, such as statistical model checking, estimate the likelihood that a property is satisfied by sampling executions out of the stochastic model. We propose a methodology for efficiently estimating the likelihood that a LTL property P holds of a stochastic model of a biochemical network. As with other statistical verification techniques, the methodology we propose uses a stochastic simulation algorithm for generating execution samples, however there are three key aspects that improve the efficiency: first, the sample generation is driven by on-the-fly verification of P which results in optimal overall simulation time. Second, the confidence interval estimation for the probability of P to hold is based on an efficient variant of the Wilson method which ensures a faster convergence. Third, the whole methodology is designed according to a parallel fashion and a prototype software tool has been implemented that performs the sampling/verification process in parallel over an HPC architecture

Analysis of the Macaca mulatta transcriptome and the sequence divergence between Macaca and human

We report the initial sequencing and comparative analysis of the Macaca mulatta transcriptome. Cloned sequences from 11 tissues, nine animals, and three species (M. mulatta, M. fascicularis, and M. nemestrina) were sampled, resulting in the generation of 48,642 sequence reads. These data represent an initial sampling of the putative rhesus orthologs for 6,216 human genes. Mean nucleotide diversity within M. mulatta and sequence divergence among M. fascicularis, M. nemestrina, and M. mulatta are also reported

On religion and cultural policy: notes on the Roman Catholic Church

This paper argues that religious institutions have largely been neglected within the study of cultural policy. This is attributed to the inherently secular tendency of most modern social sciences. Despite the predominance of the ‘secularisation paradigm’, the paper notes that religion continues to promote powerful attachments and denunciations. Arguments between the ‘new atheists’, in particular, Richard Dawkins, and their opponents are discussed, as is Habermas’s conciliatory encounter with Joseph Ratzinger (later Pope Benedict XVI). The paper then moves to a consideration of the Roman Catholic Church as an agent of cultural policy, whose overriding aim is the promotion of ‘Christian consciousness’. Discussion focuses on the contested meanings of this, with reference to (1) the deliberations of Vatican II and (2) the exercise of theological and cultural authority by the Pope and the Congregation for the Doctrine of the Faith (CDF). It is argued that these doctrinal disputes intersect with secular notions of social and cultural policy and warrant attention outside the specialist realm of theological discourse

Cisplatin-induced emesis: systematic review and meta-analysis of the ferret model and the effects of 5-HT3 receptor antagonists

PURPOSE: The ferret cisplatin emesis model has been used for ~30 years and enabled identification of clinically used anti-emetics. We provide an objective assessment of this model including efficacy of 5-HT(3) receptor antagonists to assess its translational validity. METHODS: A systematic review identified available evidence and was used to perform meta-analyses. RESULTS: Of 182 potentially relevant publications, 115 reported cisplatin-induced emesis in ferrets and 68 were included in the analysis. The majority (n = 53) used a 10 mg kg(−1) dose to induce acute emesis, which peaked after 2 h. More recent studies (n = 11) also used 5 mg kg(−1), which induced a biphasic response peaking at 12 h and 48 h. Overall, 5-HT(3) receptor antagonists reduced cisplatin (5 mg kg(−1)) emesis by 68% (45–91%) during the acute phase (day 1) and by 67% (48–86%) and 53% (38–68%, all P < 0.001), during the delayed phase (days 2, 3). In an analysis focused on the acute phase, the efficacy of ondansetron was dependent on the dosage and observation period but not on the dose of cisplatin. CONCLUSION: Our analysis enabled novel findings to be extracted from the literature including factors which may impact on the applicability of preclinical results to humans. It reveals that the efficacy of ondansetron is similar against low and high doses of cisplatin. Additionally, we showed that 5-HT(3) receptor antagonists have a similar efficacy during acute and delayed emesis, which provides a novel insight into the pharmacology of delayed emesis in the ferret

Fitness consequences of different migratory strategies in partially migratory populations: a multi-taxa meta-analysis

1.Partial migration – wherein migratory and non-migratory individuals exist within the same population – represents a behavioural dimorphism; for it to persist over time, both strategies should yield equal individual fitness. This balance may be maintained through trade-offs where migrants gain survival benefits by avoiding unfavourable conditions, while residents gain breeding benefits from early access to resources. 2.There has been little overarching quantitative analysis of the evidence for this fitness balance. As migrants – especially long-distance migrants – may be particularly vulnerable to environmental change, it is possible that recent anthropogenic impacts could drive shifts in fitness balances within these populations. 3.We tested these predictions using a multi-taxa meta-analysis. Of 2939 reviewed studies, 23 contained suitable information for meta-analysis, yielding 129 effect sizes. 4.Of these, 73% (n=94) reported higher resident fitness, 22% (n=28) reported higher migrant fitness, and 5% (n=7) reported equal fitness. Once weighted for precision, we found balanced fitness benefits across the entire dataset, but a consistently higher fitness of residents over migrants in birds and herpetofauna (the best-sampled groups). Residency benefits were generally associated with survival, not breeding success, and increased with the number of years of data over which effect sizes were calculated, suggesting deviations from fitness parity are not due to sampling artefacts. 5.A pervasive survival benefit to residency documented in recent literature could indicate that increased exposure to threats associated with anthropogenic change faced by migrating individuals may be shifting the relative fitness balance between strategies