Methylglyoxal-dependent glycative stress and deregulation of SIRT1 functional network in the ovary of PCOS mice

Advanced glycation end-products (AGEs) are involved in the pathogenesis and consequences of polycystic ovary syndrome (PCOS), a complex metabolic disorder associated with female infertility. The most powerful AGE precursor is methylglyoxal (MG), a byproduct of glycolysis, that is detoxified by the glyoxalase system. By using a PCOS mouse model induced by administration of dehydroepiandrosterone (DHEA), we investigated whether MG-dependent glycative stress contributes to ovarian PCOS phenotype and explored changes in the Sirtuin 1 (SIRT1) functional network regulating mitochondrial functions and cell survival. In addition to anovulation and reduced oocyte quality, DHEA ovaries revealed altered collagen deposition, increased vascularization, lipid droplets accumulation and altered steroidogenesis. Here we observed increased intraovarian MG-AGE levels in association with enhanced expression of receptor for AGEs (RAGEs) and deregulation of the glyoxalase system, hallmarks of glycative stress. Moreover, DHEA mice exhibited enhanced ovarian expression of SIRT1 along with increased protein levels of SIRT3 and superoxide dismutase 2 (SOD2), and decreased peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC1 alpha), mitochondrial transcriptional factor A (mtTFA) and translocase of outer mitochondrial membrane 20 (TOMM20). Finally, the presence of autophagy protein markers and increased AMP-activated protein kinase (AMPK) suggested the involvement of SIRT1/AMPK axis in autophagy activation. Overall, present findings demonstrate that MG-dependent glycative stress is involved in ovarian dysfunctions associated to PCOS and support the hypothesis of a SIRT1-dependent adaptive response

Shear-wave velocity structure at Mt. Etna from inversion of Rayleigh-wave dispersion patterns (2 s < T < 20 s)

In the present study, we investigated the dispersion characteristics of medium-to-long period Rayleigh waves (2 s < T < 20 s) using both singlestation techniques (multiple-filter analysis, and phase-match filter) and multichannel techniques (horizontal slowness [p] and angular frequency [~] stack, and cross-correlation) to determine the velocity structure for the Mt. Etna volcano. We applied these techniques to a dataset of teleseisms, as regional and local earthquakes recorded by two broad-band seismic arrays installed at Mt. Etna in 2002 and 2005, during two seismic surveys organized by the Istituto Nazionale di Geofisica e Vulcanologia (INGV), sezione di Napoli. The dispersion curves obtained showed phase velocities ranging from 1.5 km/s to 4.0 km/s in the frequency band 0.05 Hz to 0.45 Hz. We inverted the average phase velocity dispersion curves using a non-linear approach, to obtain a set of shear-wave velocity models with maximum resolution depths of 25 km to 30 km. Moreover, the presence of lateral velocity contrasts was checked by dividing the whole array into seven triangular sub-arrays and inverting the dispersion curves relative to each triangle

Globular Clusters around Galaxies in Groups

We have obtained deep photometry of NGC 1199 (in HCG 22) and NGC 6868 (in the Telescopium group). Both galaxies are the optically brightest galaxies of their groups. Our analysis of B and R images taken with the Keck II and the VLT/ESO telescopes, detected a population of globular clusters around both galaxies, with total specific frequencies S_N=1.7\pm0.6 for NGC 1199 and S_N = 1.3\pm0.6 for NGC 6868. The color distributions of the globular cluster systems shows bimodal peaks centered at (B-R)_0 = 1.13\pm0.10 and 1.42\pm0.10 (NGC 1199) and (B-R)_0=1.12\pm0.10 and 1.42\pm0.10 (NGC 6868).Comment: 3 pages, 1 figure. To appear in the proceedings of IAU Symp. 207, "Extragalactic Star Clusters", eds. E. Grebel, D. Geisler, D. Minnit

On thermalization of magnetic nano-arrays at fabrication

We propose a model to predict and control the statistical ensemble of magnetic degrees of freedom in Artificial Spin Ice (ASI) during thermalized adiabatic growth. We predict that as-grown arrays are controlled by the temperature at fabrication and by their lattice constant, and that they can be described by an effective temperature. If the geometry is conducive to a phase transition, then the lowest temperature phase is accessed in arrays of lattice constant smaller than a critical value, which depends on the temperature at deposition. Alternatively, for arrays of equal lattice constant, there is a temperature threshold at deposition and the lowest temperature phase is accessed for fabrication temperatures {\it larger rather than smaller} than this temperature threshold. Finally we show how to define and control the effective temperature of the as-grown array and how to measure critical exponents directly. We discuss the role of kinetics at the critical point, and applications to experiments, in particular to as-grown thermalized square ASI, and to magnetic monopole crystallization in as-grown honeycomb ASI.Comment: 14 pages, 2 figures. A theoretical approach to experimental results reported in: Morgan J P, Stein A, Langridge S and Marrows C (2010) Nature Physics 7 7

Magnetized Tolman-Bondi Collapse

We investigate the gravitational implosion of magnetized matter by studying the inhomogeneous collapse of a weakly magnetized Tolman-Bondi spacetime. The role of the field is analyzed by looking at the convergence of neighboring particle worldlines. In particular, we identify the magnetically related stresses in the Raychaudhuri equation and use the Tolman-Bondi metric to evaluate their impact on the collapsing dust. We find that, despite the low energy level of the field, the Lorentz force dominates the advanced stages of the collapse, leading to a strongly anisotropic contraction. In addition, of all the magnetic stresses, those that resist the collapse are found to grow faster.Comment: 6 pages, RevTex; v2: physical interpretation of the results slightly changed, references added, version accepted in Phys. Rev. D (2006

Levers and Obstacles of Effective Research and Innovation for Organic Food and Farming in Italy

The objectives of this paper are to present the dynamic of organic food and farming (OFF) research and innovation, to outline challenges in deploying programs and accessing funding, and to define key actions to foster the development of tailored quality research on organic farming in Italy. The baseline starts from the main outcomes that emerged during the World Caf\ue9 held in the frame of the Salone Internazionale del biologico e del naturale (SANA Expo) in 2018, where the Italian OFF research community met to build a convergence on scope and modus operandi in the research endeavor. These outcomes were examined in the light of the key features of the research and innovation projects funded in Italy in the last 10 years, respectively by the Italian Ministry of Agriculture and the regional administrations through the innovation support instruments in the Rural Development Plan programming periods. In the period 2009\u20132018, 70 research projects for a total funding of 21.081 million \ubf (&lt;0.1% of the value of the sector) were launched, addressing nine dierent topic areas. Over a similar period (2007\u20132019), 53 regional innovation projects addressing organic farming were activated for a total budget of 14.299 million \ubf (&lt;10% of the entire available funding). The implementation of interventions in the research and the innovation areas were often scattered in terms of the topics, disciplines, and types of supply chain/network addressed. The relatively high share of multi/interdisciplinary research and innovation projects aswell as the acknowledgement of the multi-actor approach as a fundamental step toward co-research and co-innovation were upshots that emerged from our analysis. The outcomes of this study can be used by competent national and the regional authorities to design their future research and innovation policies and interventions

On the development of selective chelators for Cadmium: Synthesis, structure and chelating properties of 3-((5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl)amino)benzo[d]isothiazole 1,1-dioxide, a novel Thiadiazolyl Saccharinate

Aquatic contamination by heavy metals is a major concern for the serious negative consequences it has for plants, animals, and humans. Among the most toxic metals, Cd(II) stands out since selective and truly efficient methodologies for its removal are not known. We report a novel multidentate chelating agent comprising the heterocycles thiadiazole and benzisothiazole. 3-((5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl)amino)benzo[d]isothiazole 1,1-dioxide (AL14) was synthesized from cheap saccharin and characterized by different techniques, including single crystal X-ray crystallography. Our studies revealed the efficiency and selectivity of AL14 for the chelation of dissolved Cd(II) (as compared to Cu(II) and Fe(II)). Different spectral changes were observed upon the addition of Cd(II) and Cu(II) during UV-Vis titrations, suggesting different complexation interactions with both metals.UIDB/04326/2020, UIDB/04564/2020, ALG-01-0145-FEDER-022121, SFRH/BD/130407/2017info:eu-repo/semantics/publishedVersio

Synthesis, structure and antileishmanial evaluation of endoperoxide–pyrazole hybrids

Leishmaniases are among the most impacting neglected tropical diseases. In attempts to repurpose antimalarial drugs or candidates, it was found that selected 1,2,4-trioxanes, 1,2,4,5-tetraoxanes, and pyrazole-containing chemotypes demonstrated activity against Leishmania parasites. This study reports the synthesis and structure of trioxolane–pyrazole (OZ1, OZ2) and tetraoxane–pyrazole (T1, T2) hybrids obtained from the reaction of 3(5)-aminopyrazole with endoperoxide-containing building blocks. Interestingly, only the endocyclic amine of 3(5)-aminopyrazole was found to act as nucleophile for amide coupling. However, the fate of the reaction was influenced by prototropic tautomerism of the pyrazole heterocycle, yielding 3- and 5-aminopyrazole containing hybrids which were characterized by different techniques, including X-ray crystallography. The compounds were evaluated for in vitro antileishmanial activity against promastigotes of L. tropica and L. infantum, and for cytotoxicity against THP-1 cells. Selected compounds were also evaluated against intramacrophage amastigote forms of L. infantum. Trioxolane–pyrazole hybrids OZ1 and OZ2 exhibited some activity against Leishmania promastigotes, while tetraoxane–pyrazole hybrids proved inactive, most likely due to solubility issues. Eight salt forms, specifically tosylate, mesylate, and hydrochloride salts, were then prepared to improve the solubility of the corresponding peroxide hybrids and were uniformly tested. Biological evaluations in promastigotes showed that the compound OZ1•HCl was the most active against both strains of Leishmania. Such finding was corroborated by the results obtained in assessments of the L. infantum amastigote susceptibility. It is noteworthy that the salt forms of the endoperoxide–pyrazole hybrids displayed a broader spectrum of action, showing activity in both strains of Leishmania. Our preliminary biological findings encourage further optimization of peroxide–pyrazole hybrids to identify a promising antileishmanial lead.info:eu-repo/semantics/publishedVersio

Affiliative bonds and cruel behavior in childhood interspecific relationships: A conceptual framework on the psychodynamics of affect regulation

Background: Childhood interspecific relationships can be viewed as a mirror of the person’s capacity to interact with other living beings. The interspecific relationship can involve different attachment styles, affect regulation skills, transitional object dynamics, and self-awareness and mentalization processes. Yet interspecific relationships can also be disrupted, since they can be associated with cruel behavior toward animals, which is in turn related to possible psychopathology. Method: We provided a conceptual framework based on the literature addressing the interspecific relationship in both its adaptive and positive features as well as in its disrupted aspects. Discussion: Pets have often been regarded as attachment figures that can aid children in socialization and growth processes. They have been deemed to represent “social catalysts” that tend to facilitate human relationships, thus increasing prosocial behaviors. On the dark side of the pet-child interaction, childhood abuse of animals tends to be associated with behavioral and emotional problems that have been thought of as underlying psychopathology (e.g., conduct disorder and antisocial personality traits). Childhood cruelty to animals seems to accompany emotion dysregulation, poor social information processing, and low empathy. Conclusions: Since the child-pet relationship has substantial implications for the individual’s mental health and for the potential development of psychopathology, addressing children’s attitudes toward animals can aid in understanding the affective and emotional dimensions of their interpersonal experience

Inhibition of C5aR1 as a promising approach to treat taxane-induced neuropathy

: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of several antitumor agents resulting in progressive and often irreversible damage of peripheral nerves. In addition to their known anticancer effects, taxanes, including paclitaxel, can also induce peripheral neuropathy by activating microglia and astrocytes, which release pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 1-beta (IL-1β), and chemokine (C-C motif) ligand 2 (CCL-2). All these events contribute to the maintenance of neuropathic or inflammatory response. Complement component 5a (C5a)/C5a receptor 1 (C5aR1) signaling was very recently shown to play a crucial role in paclitaxel-induced peripheral neuropathy. Our recent findings highlighted that taxanes have the previously unreported property of binding and activating C5aR1, and that C5aR1 inhibition by DF3966A is effective in preventing paclitaxel-induced peripheral neuropathy (PIPN) in animal models. Here, we investigated if C5aR1 inhibition maintains efficacy in reducing PIPN in a therapeutic setting. Furthermore, we characterized the role of C5aR1 activation by paclitaxel and the CIPN-associated activation of nod-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome. Our results clearly show that administration of the C5aR1 inhibitor strongly reduced cold and mechanical allodynia in mice when given both during the onset of PIPN and when neuropathy is well established. C5aR1 activation by paclitaxel was found to be a key event in the induction of inflammatory factors in spinal cord, such as TNF-α, ionized calcium-binding adapter molecule 1 (Iba-1), and glial fibrillary acidic protein (GFAP). In addition, C5aR1 inhibition significantly mitigated paclitaxel-induced inflammation and inflammasome activation by reducing IL-1β and NLRP3 expression at both sciatic and dorsal root ganglia level, confirming the involvement of inflammasome in PIPN. Moreover, paclitaxel-induced upregulation of C5aR1 was significantly reduced by DF3966A treatment in central nervous system. Lastly, the antinociceptive effect of C5aR1 inhibition was confirmed in an in vitro model of sensory neurons in which we focused on receptor channels usually activated upon neuropathy. In conclusion, C5aR1 inhibition is proposed as a therapeutic option with the potential to exert long-term protective effect on PIPN-associated neuropathic pain and inflammation