The phosphodiesterase 5 inhibitor sildenafil decreases the proinflammatory chemokine IL-8 in diabetic cardiomyopathy: in vivo and in vitro evidence

Purpose: Interleukin (IL)-8 is a proinflammatory C-X-C chemokine involved in inflammation underling cardiac diseases, primary or in comorbid condition, such diabetic cardiomyopathy (DCM). The phosphodiesterase type 5 inhibitor sildenafil can ameliorate cardiac conditions by counteracting inflammation. The study aim is to evaluate the effect of sildenafil on serum IL-8 in DCM subjects vs. placebo, and on IL-8 release in human endothelial cells (Hfaec) and peripheral blood mononuclear cells (PBMC) under inflammatory stimuli. Methods: IL-8 was quantified: in sera of (30) DCM subjects before (baseline) and after sildenafil (100 mg/day, 3-months) vs. (16) placebo and (15) healthy subjects, by multiplatform array; in supernatants from inflammation-challenged cells after sildenafil (1 µM), by ELISA. Results: Baseline IL-8 was higher in DCM vs. healthy subjects (149.14 ± 46.89 vs. 16.17 ± 5.38 pg/ml, p < 0.01). Sildenafil, not placebo, significantly reduced serum IL-8 (23.7 ± 5.9 pg/ml, p < 0.05 vs. baseline). Receiver operating characteristic (ROC) curve for IL-8 was 0.945 (95% confidence interval of 0.772 to 1.0, p < 0.01), showing good capacity of discriminating the response in terms of drug-induced IL-8 decrease (sensitivity of 0.93, specificity of 0.90). Sildenafil significantly decreased IL-8 protein release by inflammation-induced Hfaec and PBMC and downregulated IL-8 mRNA in PBMC, without affecting cell number or PDE5 expression. Conclusion: Sildenafil might be suggested as potential novel pharmacological tool to control DCM progression through IL-8 targeting at systemic and cellular level

Relationships between Meiofaunal Biodiversity and Prokaryotic Heterotrophic Production in Different Tropical Habitats and Oceanic Regions

Tropical marine ecosystems are among the most diverse of the world oceans, so that assessing the linkages between biodiversity and ecosystem functions (BEF) is a crucial step to predict consequences of biodiversity loss. Most BEF studies in marine ecosystems have been carried out on macrobenthic diversity, whereas the influence of the meiofauna on ecosystem functioning has received much less attention. We compared meiofaunal and nematode biodiversity and prokaryotic heterotrophic production across seagrass, mangrove and reef sediments in the Caribbean, Celebes and Red Seas. For all variables we report the presence of differences among habitats within the same region, and among regions within the same habitat. In all regions, the richness of meiofaunal taxa in reef and seagrass sediments is higher than in mangrove sediments. The sediments of the Celebes Sea show the highest meiofaunal biodiversity. The composition of meiofaunal assemblages varies significantly among habitats in the same region. The nematode beta diversity among habitats within the same region is higher than the beta diversity among regions. Although one site per habitat was considered in each region, these results suggest that the composition of meiofaunal assemblages varies primarily among biogeographic regions, whereas the composition of nematode assemblages varies more considerably among habitats. Meiofauna and nematode biodiversity and prokaryotic heterotrophic production, even after the removal of covariate effects linked with longitude and the quantity and nutritional quality of organic matter, are positively and linearly linked both across regions and within each habitat type. Our results confirm that meiofauna and nematode biodiversity may influence benthic prokaryotic activity, which, in turn, implies that diversity loss could have negative impacts on ecosystem functioning in these systems

Testosterone insulin-like effects: an in vitro study on the short-term metabolic effects of testosterone in human skeletal muscle cells

Testosterone by promoting different metabolic pathways contributes to short-term homeostasis of skeletal muscle, the largest insulin-sensitive tissue and the primary site for insulin-stimulated glucose utilization. Despite evidences indicate a close relationship between testosterone and glucose metabolism, the molecular mechanisms responsible for a possible testosterone-mediated insulin-like effects on skeletal muscle are still unknown

Post-Newtonian gravitational radiation and equations of motion via direct integration of the relaxed Einstein equations. III. Radiation reaction for binary systems with spinning bodies

Using post-Newtonian equations of motion for fluid bodies that include radiation-reaction terms at 2.5 and 3.5 post-Newtonian (PN) order (O[(v/c)^5] and O[(v/c)^7] beyond Newtonian order), we derive the equations of motion for binary systems with spinning bodies. In particular we determine the effects of radiation-reaction coupled to spin-orbit effects on the two-body equations of motion, and on the evolution of the spins. For a suitable definition of spin, we reproduce the standard equations of motion and spin-precession at the first post-Newtonian order. At 3.5PN order, we determine the spin-orbit induced reaction effects on the orbital motion, but we find that radiation damping has no effect on either the magnitude or the direction of the spins. Using the equations of motion, we find that the loss of total energy and total angular momentum induced by spin-orbit effects precisely balances the radiative flux of those quantities calculated by Kidder et al. The equations of motion may be useful for evolving inspiraling orbits of compact spinning binaries.Comment: 19 pages, small corrections, equivalent to published versio

Red coral extinction risk enhanced by ocean acidification

The red coral Corallium rubrum is a habitat-forming species with a prominent and structural role in mesophotic habitats, which sustains biodiversity hotspots. This precious coral is threatened by both over-exploitation and temperature driven mass mortality events. We report here that biocalcification, growth rates and polyps’ (feeding) activity of Corallium rubrum are significantly reduced at pCO2 scenarios predicted for the end of this century (0.2 pH decrease). Since C. rubrum is a long-living species (.200 years), our results suggest that ocean acidification predicted for 2100 will significantly increases the risk of extinction of present populations. Given the functional role of these corals in the mesophotic zone, we predict that ocean acidification might have cascading effects on the functioning of these habitats worldwid

Unveiling the biodiversity of deep-sea nematodes through metabarcoding: Are we ready to bypass the classical taxonomy?

Nematodes inhabiting benthic deep-sea ecosystems account for >90% of the total metazoan abundances and they have been hypothesised to be hyper-diverse, but their biodiversity is still largely unknown. Metabarcoding could facilitate the census of biodiversity, especially for those tiny metazoans for which morphological identification is difficult. We compared, for the first time, different DNA extraction procedures based on the use of two commercial kits and a previously published laboratory protocol and tested their suitability for sequencing analyses of 18S rDNA of marine nematodes. We also investigated the reliability of Roche 454 sequencing analyses for assessing the biodiversity of deep-sea nematode assemblages previously morphologically identified. Finally, intra-genomic variation in 18S rRNA gene repeats was investigated by Illumina MiSeq in different deep-sea nematode morphospecies to assess the influence of polymorphisms on nematode biodiversity estimates. Our results indicate that the two commercial kits should be preferred for the molecular analysis of biodiversity of deep-sea nematodes since they consistently provide amplifiable DNA suitable for sequencing. We report that the morphological identification of deep-sea nematodes matches the results obtained by metabarcoding analysis only at the order-family level and that a large portion of Operational Clustered Taxonomic Units (OCTUs) was not assigned. We also show that independently from the cut-off criteria and bioinformatic pipelines used, the number of OCTUs largely exceeds the number of individuals and that 18S rRNA gene of different morpho-species of nematodes displayed intragenomic polymorphisms. Our results indicate that metabarcoding is an important tool to explore the diversity of deep-sea nematodes, but still fails in identifying most of the species due to limited number of sequences deposited in the public databases, and in providing quantitative data on the species encountered. These aspects should be carefully taken into account before using metabarcoding in quantitative ecological research and monitoring programmes of marine biodiversity

Perturbative Expansion in the Galilean Invariant Spin One-Half Chern-Simons Field Theory

A Galilean Chern-Simons field theory is formulated for the case of two interacting spin-1/2 fields of distinct masses M and M'. A method for the construction of states containing N particles of mass M and N' particles of mass M' is given which is subsequently used to display equivalence to the spin-1/2 Aharonov-Bohm effect in the N = N' =1 sector of the model. The latter is then studied in perturbation theory to determine whether there are divergences in the fourth order (one loop) diagram. It is found that the contribution of that order is finite (and vanishing) for the case of parallel spin projections while the antiparallel case displays divergences which are known to characterize the spin zero case in field theory as well as in quantum mechanics.Comment: 14 pages LaTeX, including 2 figures using eps

Spin precession in the Schwarzschild spacetime: circular orbits

We study the behavior of nonzero rest mass spinning test particles moving along circular orbits in the Schwarzschild spacetime in the case in which the components of the spin tensor are allowed to vary along the orbit, generalizing some previous work.Comment: To appear on Classical and Quantum Gravity, 200

Relativistic Quantum Mechanics and Relativistic Entanglement in the Rest-Frame Instant Form of Dynamics

A new formulation of relativistic quantum mechanics is proposed in the framework of the rest-frame instant form of dynamics with its instantaneous Wigner 3-spaces and with its description of the particle world-lines by means of derived non-canonical predictive coordinates. In it we quantize the frozen Jacobi data of the non-local 4-center of mass and the Wigner-covariant relative variables in an abstract (frame-independent) internal space whose existence is implied by Wigner-covariance. The formalism takes care of the properties of both relativistic bound states and scattering ones. There is a natural solution to the \textit{relativistic localization problem}. The non-relativistic limit leads to standard quantum mechanics but with a frozen Hamilton-Jacobi description of the center of mass. Due to the \textit{non-locality} of the Poincar\'e generators the resulting theory of relativistic entanglement is both \textit{kinematically non-local and spatially non-separable}: these properties, absent in the non-relativistic limit, throw a different light on the interpretation of the non-relativistic quantum non-locality and of its impact on foundational problems.Comment: 73 pages, includes revision

Guided bone regeneration using titanium mesh to augment 3-dimensional alveolar defects prior to implant placement. A pilot study

Objectives: To evaluate the outcomes of bone regeneration using a customized titanium mesh scaffold to cover a bone graft for reconstruction of complex defects of the jaws. Materials and Methods: 19 large defects were digitally reconstructed using CT scans according to the prosthetic requirements. A titanium mesh scaffold was designed to cover the bone (autologous/bovine bone particulate) graft. At least 6 months after surgery, a new cone-beam CT was taken. The pre- and postoperative CT datasets were then converted into three-dimensional models and digitally aligned. The actual mesh position was compared to the virtual position to assess the reliability of the digital project. The reconstructed bone volumes (RBVs) were calculated according to the planned bone volumes (PBVs), outlining the areas under the mesh. These values were then correlated with the number of exposures, locations of atrophy, and virtually planned bone volume. Results: The mean matching value between the planned position of the mesh and the actual one was 82 ± 13.4%. 52.3% (40% early and 60% late) exposures were observed, with 15.8% exhibiting infection. 26.3% resulted as failures. The amount of reconstructed bone volume (RBV) in respect to PBV was 65 ± 40.5%, including failures, and 88.2 ± 8.32% without considering the failures. The results of the exposure event were statistically significant (p =.006) in conditioning the bone volume regenerated. Conclusions: This study obtained up to 88% of bone regeneration in 74% of the cases. The failures encountered (26%) should underline the operator's expertise relevance in conditioning the final result