Regulation by phosphodiesterase isoforms of protein kinase A-mediated attenuation of myocardial protein kinase D activation

Protein kinase D (PKD) targets several proteins in the heart, including cardiac troponin I (cTnI) and class II histone deacetylases, and regulates cardiac contraction and hypertrophy. In adult rat ventricular myocytes (ARVM), PKD activation by endothelin-1 (ET1) occurs via protein kinase Cε and is attenuated by cAMP-dependent protein kinase (PKA). Intracellular compartmentalisation of cAMP, arising from localised activity of distinct cyclic nucleotide phosphodiesterase (PDE) isoforms, may result in spatially constrained regulation of the PKA activity that inhibits PKD activation. We have investigated the roles of the predominant cardiac PDE isoforms, PDE2, PDE3 and PDE4, in PKA-mediated inhibition of PKD activation. Pretreatment of ARVM with the non-selective PDE inhibitor isobutylmethylxanthine (IBMX) attenuated subsequent PKD activation by ET1. However, selective inhibition of PDE2 [by erythro-9-(2-hydroxy-3-nonyl) adenine, EHNA], PDE3 (by cilostamide) or PDE4 (by rolipram) individually had no effect on ET1-induced PKD activation. Selective inhibition of individual PDE isoforms also had no effect on the phosphorylation status of the established cardiac PKA substrates phospholamban (PLB; at Ser16) and cTnI (at Ser22/23), which increased markedly with IBMX. Combined administration of cilostamide and rolipram, like IBMX alone, attenuated ET1-induced PKD activation and increased PLB and cTnI phosphorylation, while combined administration of EHNA and cilostamide or EHNA and rolipram was ineffective. Thus, cAMP pools controlled by PDE3 and PDE4, but not PDE2, regulate the PKA activity that inhibits ET1-induced PKD activation. Furthermore, PDE3 and PDE4 play redundant roles in this process, such that inhibition of both isoforms is required to achieve PKA-mediated attenuation of PKD activation

Inferring Long-term Dynamics of Ecological Communities Using Combinatorics

In an increasingly changing world, predicting the fate of species across the globe has become a major concern. Understanding how the population dynamics of various species and communities will unfold requires predictive tools that experimental data alone can not capture. Here, we introduce our combinatorial framework, Widespread Ecological Networks and their Dynamical Signatures (WENDyS) which, using data on the relative strengths of interactions and growth rates within a community of species predicts all possible long-term outcomes of the community. To this end, WENDyS partitions the multidimensional parameter space (formed by the strengths of interactions and growth rates) into a finite number of regions, each corresponding to a unique set of coarse population dynamics. Thus, WENDyS ultimately creates a library of all possible outcomes for the community. On the one hand, our framework avoids the typical ``parameter sweeps'' that have become ubiquitous across other forms of mathematical modeling, which can be computationally expensive for ecologically realistic models and examples. On the other hand, WENDyS opens the opportunity for interdisciplinary teams to use standard experimental data (i.e., strengths of interactions and growth rates) to filter down the possible end states of a community. To demonstrate the latter, here we present a case study from the Indonesian Coral Reef. We analyze how different interactions between anemone and anemonefish species lead to alternative stable states for the coral reef community, and how competition can increase the chance of exclusion for one or more species. WENDyS, thus, can be used to anticipate ecological outcomes and test the effectiveness of management (e.g., conservation) strategies.Comment: 25 pages, 9 figure

Identification of the relative distribution of rare-earth ions in phosphate glasses

The relative distribution of rare-earth ions R3+ (Dy3+ or Ho3+) in the phosphate glass RAl0.30P3.05O9.62 was measured by employing the method of isomorphic substitution in neutron diffraction. It is found that 7.9(7) R-R nearest neighbors reside at 5.62(6) Angstrom in a network made from interlinked PO4 tetrahedra. Provided that the role of Al is explicitly considered, a self-consistent account of the local matrix atom correlations can be developed in which there are 1.68(9) bridging and 2.32(9) terminal oxygen atoms per phosphorus

Structure of lanthanum and cerium phosphate glasses by the method of isomorphic substitution in neutron diffraction

Neutron diffraction was used to measure the total structure factors for several rare-earth ion R3+ (La3+ or Ce3+) phosphate glasses with composition close to RAl0.35P3.24O10.12. By assuming isomorphic structures, difference function methods were employed to separate, essentially, those correlations involving R3+ from the remainder. A self-consistent model of the glass structure was thereby developed in which the Al correlations were taken into explicit account. The glass network was found to be made from interlinked PO4 tetrahedra having 2.2(1) terminal oxygen atoms, OT, at 1.51(1) Angstrom, and 1.8(1) bridging oxygen atoms, OB, at 1.60(1) Angstrom. Rare-earth cations bonded to an average of 7.5(2) OT nearest neighbors in a broad and asymmetric distribution. The Al3+ ion acted as a network modifier and formed OT-A1-OT linkages that helped strengthen the glass. The connectivity of the R-centered coordination polyhedra was quantified in terms of a parameter f(s) and used to develop a model for the dependence on composition of the A1-OT coordination number in R-A1-P-O glasses. By using recent 17 A1 nuclear-magnetic-resonance data, it was shown that this connectivity decreases monotonically with increasing Al content. The chemical durability of the glasses appeared to be at a maximum when the connectivity of the R-centered coordination polyhedra was at a minimum. The relation of f(s) to the glass transition temperature, Tg, was discussed

Normal response to tibial neurodynamic test in asymptomatic subjects

BACKGROUND: The straight leg raise test (SLR) is one of the most performed physical tests for mechanosensitivity and impairment of the nervous system. According to the anatomy of the tibial nerve, ankle dorsiflexion and eversion movements could be used to perform the tibial neurodynamic test (TNT). To date, no study has documented the normal responses of the TNT. OBJECTIVE: To document normal responses of the TNT in asymptomatic individuals and to investigate influences from sex and leg dominance. METHODS: A cross-sectional study with 44 asymptomatic volunteer subjects, a total of 88 lower limbs, was carried out. The range of motion (ROM), quality, and distribution of sensory responses were recorded. The hip flexion ROM was measured when subjects reported an intensity of their symptoms of 2/10 (P1) and 8/10 (P2). RESULTS: The mean ROM for hip flexion at P1 was 44.22 ± 13.13 and 66.73 ± 14.30 at P2. Hip flexion was significantly greater at P2 than P1 (p 0.05). The descriptor of the quality of sensory responses most often used by participants was stretching (88.6% and 87.5% for P1 and P2, respectively) in the popliteal fossa and posterior calf. CONCLUSIONS: This study describes the sensory responses of asymptomatic subjects resulting from the TNT. Our findings indicate that TNT responses are independent of the influence of sex or leg dominance

Thermal torque effects on the migration of growing low-mass planets

As planets grow the exchange of angular momentum with the gaseous component ofthe protoplanetary disc produces a net torque resulting in a variation of the semi-major axis of the planet. For low-mass planets not able to open a gap in the gaseousdisc this regime is known as type I migration. Pioneer works studied this mechanismin isothermal discs finding fast inward type I migration rates that were unable toreproduce the observed properties of extrasolar planets. In the last years, several im-provements have been made in order to extend the study of type I migration rates tonon-isothermal discs. Moreover, it was recently shown that if the planet?s luminositydue to solid accretion is taken into account, inward migration could be slowed downand even reversed. In this work, we study the planet formation process incorporating,and comparing, updated type I migration rates for non-isothermal discs and the role ofplanet?s luminosity over such rates. We find that the latter can have important effectson planetary evolution, producing a significant outward migration for the growingplanets.Fil: Guilera, Octavio Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Cuello, N.. Pontificia Universidad Católica de Chile; ChileFil: Montesinos, M.. Universidad de Valparaíso; ChileFil: Miller Bertolami, Marcelo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Ronco, María Paula. Pontificia Universidad Católica de Chile; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Cuadra, J.. Pontificia Universidad Católica de Chile; ChileFil: Masset, F. S.. Universidad Autonoma de Mexico; Méxic

Identification of differentially expressed genes profiles in a combined mouse model of Parkinsonism and colitis

©2020. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/ This document is the Published, version of a Published Work that appeared in final form in Scientific Reports. To access the final edited and published work see https://doi.org/10.1038/s41598-020-69695-

Nematic state of the FeSe superconductor

We study the crystal structure of the tetragonal iron selenide FeSe and its nematic phase transition to the low-temperature orthorhombic structure using synchrotron x-ray and neutron scattering analyzed in both real space and reciprocal space. We show that in the local structure the orthorhombic distortion associated with the electronically driven nematic order is more pronounced at short length scales. It also survives to temperatures above 90 K, where reciprocal-space analysis suggests tetragonal symmetry. Additionally, the real-space pair distribution function analysis of the synchrotron x-ray diffraction data reveals a tiny broadening of the peaks corresponding to the nearest Fe-Fe, nearest Fe-Se, and next-nearest Fe-Se bond distances as well as the tetrahedral torsion angles at a short length scale of 20 Å. This broadening appears below 20 K and is attributed to a pseudogap. However, we did not observe any further reduction in local symmetry below orthorhombic down to 3 K. Our results suggest that the superconducting gap anisotropy in FeSe is not associated with any symmetry-lowering short-range structural correlations