The diversification and lineage-specific expansion of nitric oxide signaling in Placozoa: insights in the evolution of gaseous transmission.

Nitric oxide (NO) is a ubiquitous gaseous messenger, but we know little about its early evolution. Here, we analyzed NO synthases (NOS) in four different species of placozoans-one of the early-branching animal lineages. In contrast to other invertebrates studied, Trichoplax and Hoilungia have three distinct NOS genes, including PDZ domain-containing NOS. Using ultra-sensitive capillary electrophoresis assays, we quantified nitrites (products of NO oxidation) and L-citrulline (co-product of NO synthesis from L-arginine), which were affected by NOS inhibitors confirming the presence of functional enzymes in Trichoplax. Using fluorescent single-molecule in situ hybridization, we showed that distinct NOSs are expressed in different subpopulations of cells, with a noticeable distribution close to the edge regions of Trichoplax. These data suggest both the compartmentalized release of NO and a greater diversity of cell types in placozoans than anticipated. NO receptor machinery includes both canonical and novel NIT-domain containing soluble guanylate cyclases as putative NO/nitrite/nitrate sensors. Thus, although Trichoplax and Hoilungia exemplify the morphologically simplest free-living animals, the complexity of NO-cGMP-mediated signaling in Placozoa is greater to those in vertebrates. This situation illuminates multiple lineage-specific diversifications of NOSs and NO/nitrite/nitrate sensors from the common ancestor of Metazoa and the preservation of conservative NOS architecture from prokaryotic ancestors

Orientational pinning and transverse voltage: Simulations and experiments in square Josephson junction arrays

We study the dependence of the transport properties of square Josephson Junctions arrays with the direction of the applied dc current, both experimentally and numerically. We present computational simulations of current-voltage curves at finite temperatures for a single vortex in the array ($Ha^2/\Phi_0=f=1/L^2$), and experimental measurements in $100\times1000$ arrays under a low magnetic field corresponding to $f\approx0.02$. We find that the transverse voltage vanishes only in the directions of maximum symmetry of the square lattice: the [10] and [01] direction (parallel bias) and the [11] direction (diagonal bias). For orientations different than the symmetry directions, we find a finite transverse voltage which depends strongly on the angle $\phi$ of the current. We find that vortex motion is pinned in the [10] direction ($\phi=0$), meaning that the voltage response is insensitive to small changes in the orientation of the current near $\phi=0$. We call this phenomenon orientational pinning. This leads to a finite transverse critical current for a bias at $\phi=0$ and to a transverse voltage for a bias at $\phi\not=0$. On the other hand, for diagonal bias in the [11] direction the behavior is highly unstable against small variations of $\phi$, leading to a rapid change from zero transverse voltage to a large transverse voltage within a few degrees. This last behavior is in good agreement with our measurements in arrays with a quasi-diagonal current drive.Comment: 9 pages, 9 figure

Screening current effects in Josephson junction arrays

The purpose of this work is to compare the dynamics of arrays of Josephson junctions in presence of magnetic field in two different frameworks: the so called XY frustrated model with no self inductance and an approach that takes into account the screening currents (considering self inductances only). We show that while for a range of parameters the simpler model is sufficiently accurate, in a region of the parameter space solutions arise that are not contained in the XY model equations.Comment: Figures available from the author

Quantum effects in a superconducting glass model

We study disordered Josephson junctions arrays with long-range interaction and charging effects. The model consists of two orthogonal sets of positionally disordered $N$ parallel filaments (or wires) Josephson coupled at each crossing and in the presence of a homogeneous and transverse magnetic field. The large charging energy (resulting from small self-capacitance of the ultrathin wires) introduces important quantum fluctuations of the superconducting phase within each filament. Positional disorder and magnetic field frustration induce spin-glass like ground state, characterized by not having long-range order of the phases. The stability of this phase is destroyed for sufficiently large charging energy. We have evaluated the temperature vs charging energy phase diagram by extending the methods developed in the theory of infinite-range spin glasses, in the limit of large magnetic field. The phase diagram in the different temperature regimes is evaluated by using variety of methods, to wit: semiclassical WKB and variational methods, Rayleigh-Schr\"{o}dinger perturbation theory and pseudospin effective Hamiltonians. Possible experimental consequences of these results are briefly discussed.Comment: 17 pages REVTEX. Two Postscript figures can be obtained from the authors. To appear in PR

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362