Skeletal muscle phenotypes initiated by ectopic MyoD in transgenic mouse heart

Forced expression of the myogenic regulatory gene MyoD in many types of cultured cells initiates their conversion into skeletal muscle. It is not known, however, if MyoD expression serves to activate all or part of the skeletal muscle program in vivo during animal development, nor is it known how limiting the influences of cellular environment may be on the regulatory effects of MyoD. To begin to address these issues, we have produced transgenic mice which express MyoD in developing heart, where neither MyoD nor its three close relatives—myogenin, Myf-5, and MRF4/herculin/Myf-6—are normally expressed. The resulting gross phenotype in offspring from multiple, independent transgenic founders includes abnormal heart morphology and ultimately leads to death. At the molecular level, affected hearts exhibit activation of skeletal muscle-specific regulatory as well as structural genes. We conclude that MyoD is able to initiate the program that leads to skeletal muscle differentiation during mouse development, even in the presence of the ongoing cardiac differentiation program. Thus, targeted misexpression of this tissue-specific regulator during mammalian embryogenesis can activate, either directly or indirectly, a diverse set of genes normally restricted to a different cell lineage and a different cellular environment

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

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

Preparing an Election Petition in Missouri

Initiative and referendum petitions provide citizens with the power to make and overturn existing laws. Through the initiative petition, the people can compel an election on the question of enacting an amendment to the Missouri Constitution or enacting a proposed law. Through the referendum petition, the people can compel an election to decide whether an existing law should be retained. The procedure to be followed in drafting these petitions is specified in the Constitution and Statutes of Missouri.Reviewed October 1993

Neurogenesis Deep Learning

Neural machine learning methods, such as deep neural networks (DNN), have achieved remarkable success in a number of complex data processing tasks. These methods have arguably had their strongest impact on tasks such as image and audio processing - data processing domains in which humans have long held clear advantages over conventional algorithms. In contrast to biological neural systems, which are capable of learning continuously, deep artificial networks have a limited ability for incorporating new information in an already trained network. As a result, methods for continuous learning are potentially highly impactful in enabling the application of deep networks to dynamic data sets. Here, inspired by the process of adult neurogenesis in the hippocampus, we explore the potential for adding new neurons to deep layers of artificial neural networks in order to facilitate their acquisition of novel information while preserving previously trained data representations. Our results on the MNIST handwritten digit dataset and the NIST SD 19 dataset, which includes lower and upper case letters and digits, demonstrate that neurogenesis is well suited for addressing the stability-plasticity dilemma that has long challenged adaptive machine learning algorithms.Comment: 8 pages, 8 figures, Accepted to 2017 International Joint Conference on Neural Networks (IJCNN 2017

Attitudes Toward Presidential Candidates in the 2012 and 2016 American Elections: Cognitive Ability and Support for Trump

Using data from the American National Election Studies, we investigated the relationship between cognitive ability and attitudes toward and actual voting for presidential candidates in the 2012 and 2016 U.S. presidential elections (i.e., Romney, Obama, Trump, and Clinton). Isolating this relationship from competing relationships, results showed that verbal ability was a significant negative predictor of support and voting for Trump (but not Romney) and a positive predictor of support and voting for Obama and Clinton. By comparing within and across the election years, our analyses revealed the nature of support for Trump, including that support for Trump was better predicted by lower verbal ability than education or income. In general, these results suggest that the 2016 U.S. presidential election had less to do with party affiliation, income, or education and more to do with basic cognitive ability

Solar-driven variation in the atmosphere of Uranus

Long-term measurements (1972-2015) of the reflectivity of Uranus at 472 and 551 nm display variability that is incompletely explained by seasonal effects. Spectral analysis shows this non-seasonal variability tracks the 11-year solar cycle. Two mechanisms could cause solar modulation, (a) nucleation onto ions or electrons created by galactic cosmic rays (GCR), or (b) UV-induced aerosol colour changes. Ion-aerosol theory is used to identify expected relationships between reflectivity fluctuations and GCR flux, tested with multiple regression and compared to the linear response predicted between reflectivity and solar UV flux. The statistics show that 24% of the variance in reflectivity fluctuations at 472 nm is explained by GCR ion-induced nucleation, compared to 22% for a UV-only mechanism. Similar GCR-related variability exists in Neptune’s atmosphere, hence the effects found at Uranus provide the first example of common variability in two planetary atmospheres driven through energetic particle modulation by their host star

Skeletal muscle phenotypes initiated by ectopic MyoD in transgenic mouse heart

Forced expression of the myogenic regulatory gene MyoD in many types of cultured cells initiates their conversion into skeletal muscle. It is not known, however, if MyoD expression serves to activate all or part of the skeletal muscle program in vivo during animal development, nor is it known how limiting the influences of cellular environment may be on the regulatory effects of MyoD. To begin to address these issues, we have produced transgenic mice which express MyoD in developing heart, where neither MyoD nor its three close relatives—myogenin, Myf-5, and MRF4/herculin/Myf-6—are normally expressed. The resulting gross phenotype in offspring from multiple, independent transgenic founders includes abnormal heart morphology and ultimately leads to death. At the molecular level, affected hearts exhibit activation of skeletal muscle-specific regulatory as well as structural genes. We conclude that MyoD is able to initiate the program that leads to skeletal muscle differentiation during mouse development, even in the presence of the ongoing cardiac differentiation program. Thus, targeted misexpression of this tissue-specific regulator during mammalian embryogenesis can activate, either directly or indirectly, a diverse set of genes normally restricted to a different cell lineage and a different cellular environment