The Gasotransmitter Hydrogen Sulfide (H₂S) Prevents Pathologic Calcification (PC) in Cartilage.

Pathologic calcification (PC) is a painful and disabling condition whereby calcium-containing crystals deposit in tissues that do not physiologically calcify: cartilage, tendons, muscle, vessels and skin. In cartilage, compression and inflammation triggered by PC leads to cartilage degradation typical of osteoarthritis (OA). The PC process is poorly understood and treatments able to target the underlying mechanisms of the disease are lacking. Here we show a crucial role of the gasotransmitter hydrogen sulfide (H <sub>2</sub> S) and, in particular, of the H <sub>2</sub> S-producing enzyme cystathionine γ-lyase (CSE), in regulating PC in cartilage. Cse deficiency (Cse KO mice) exacerbated calcification in both surgically-induced (menisectomy) and spontaneous (aging) murine models of cartilage PC, and augmented PC was closely associated with cartilage degradation (OA). On the contrary, Cse overexpression (Cse tg mice) protected from these features. In vitro, Cse KO chondrocytes showed increased calcification, potentially via enhanced alkaline phosphatase (Alpl) expression and activity and increased IL-6 production. The opposite results were obtained in Cse tg chondrocytes. In cartilage samples from patients with OA, CSE expression inversely correlated with the degree of tissue calcification and disease severity. Increased cartilage degradation in murine and human tissues lacking or expressing low CSE levels may be accounted for by dysregulated catabolism. We found higher levels of matrix-degrading metalloproteases Mmp-3 and -13 in Cse KO chondrocytes, whereas the opposite results were obtained in Cse tg cells. Finally, by high-throughput screening, we identified a novel small molecule CSE positive allosteric modulator (PAM), and demonstrated that it was able to increase cellular H <sub>2</sub> S production, and decrease murine and human chondrocyte calcification and IL-6 secretion. Together, these data implicate impaired CSE-dependent H <sub>2</sub> S production by chondrocytes in the etiology of cartilage PC and worsening of secondary outcomes (OA). In this context, enhancing CSE expression and/or activity in chondrocytes could represent a potential strategy to inhibit PC

Tuning morphology and magnetism in epitaxial L10-FePt films

In this work, well-ordered epitaxial FePt thin ¿lms have been grown by RF sputtering on two different substrates (MgO (100) and SrTiO3 (100)) and the effect of different lattice parameters between the substrate and FePt ¿lm on morphology and magnetic behavior has been considered. Growth conditions have been optimized to obtain different morphologies and magnetic behaviors

The protective role of the 3-mercaptopyruvate sulfurtransferase (3-MST)-hydrogen sulfide (H₂S) pathway against experimental osteoarthritis.

Osteoarthritis (OA) is characterized by the formation and deposition of calcium-containing crystals in joint tissues, but the underlying mechanisms are poorly understood. The gasotransmitter hydrogen sulfide (H <sub>2</sub> S) has been implicated in mineralization but has never been studied in OA. Here, we investigated the role of the H <sub>2</sub> S-producing enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) in cartilage calcification and OA development. 3-MST expression was analyzed in cartilage from patients with different OA degrees, and in cartilage stimulated with hydroxyapatite (HA) crystals. The modulation of 3-MST expression in vivo was studied in the meniscectomy (MNX) model of murine OA, by comparing sham-operated to MNX knee cartilage. The role of 3-MST was investigated by quantifying joint calcification and cartilage degradation in WT and 3-MST <sup>-/-</sup> meniscectomized knees. Chondrocyte mineralization in vitro was measured in WT and 3-MST <sup>-/-</sup> cells. Finally, the effect of oxidative stress on 3-MST expression and chondrocyte mineralization was investigated. 3-MST expression in human cartilage negatively correlated with calcification and OA severity, and diminished upon HA stimulation. In accordance, cartilage from menisectomized OA knees revealed decreased 3-MST if compared to sham-operated healthy knees. Moreover, 3-MST <sup>-/-</sup> mice showed exacerbated joint calcification and OA severity if compared to WT mice. In vitro, genetic or pharmacologic inhibition of 3-MST in chondrocytes resulted in enhanced mineralization and IL-6 secretion. Finally, oxidative stress decreased 3-MST expression and increased chondrocyte mineralization, maybe via induction of pro-mineralizing genes. 3-MST-generated H <sub>2</sub> S protects against joint calcification and experimental OA. Enhancing H <sub>2</sub> S production in chondrocytes may represent a potential disease modifier to treat OA

Tungsten oxide nanowires grown on amorphous-like tungsten films

Tungsten oxide nanowires have been synthesized by vacuum annealing in the range 500-710 °C from amorphous-like tungsten films, deposited on a Si(100) substrate by pulsed laser deposition (PLD) in the presence of a He background pressure. The oxygen required for the nanowires formation is already adsorbed in the W matrix before annealing, its amount depending on deposition parameters. Nanowire crystalline phase and stoichiometry depend on annealing temperature, ranging from W18O49-Magneli phase to monoclinic WO3. Sufficiently long annealing induces the formation of micrometer-long nanowires, up to 3.6 μm with an aspect ratio up to 90. Oxide nanowire growth appears to be triggered by the crystallization of the underlying amorphous W film, promoting their synthesis at low temperatures

Testing intermediate-age stellar evolution models with VLT photometry of LMC clusters. I. The data

This is the first of a series of three papers devoted to the calibration of a few parameters of crucial importance in the modeling of the evolution of intermediate-mass stars, with special attention to the amount of convective core overshoot. To this end we acquired deep V and R photometry for three globular clusters of the Large Magellanic Cloud (LMC), namely NGC 2173, SL 556 and NGC 2155, in the age interval 1-3 Gyr. In this first paper, we describe the aim of the project, the VLT observations and data reduction, and we make preliminary comparisons of the color-magnitude diagrams with both Padova and Yonsei-Yale isochrones. Two following papers in this series present the results of a detailed analysis of these data, independently carried out by members of the Yale and Padova stellar evolution groups. This allows us to compare both sets of models and discuss their main differences, as well as the systematic effects that they would have to the determination of the ages and metallicities of intermediate-age single stellar populations.Comment: 27 pages with 10 figures. Accepted by the Astronomical Journa

Feasibility and safety of mass drug coadministration with azithromycin and ivermectin for the control of neglected tropical diseases: a single-arm intervention trial.

BACKGROUND: Mass drug administration has made a major contribution to the public health control of several important neglected tropical diseases. For settings with more than one endemic disease, combined mass drug administration has potential practical advantages compared with separate programmes but needs confirmation of feasibility and safety. We undertook a study of mass drug administration in the Solomon Islands for trachoma and scabies control using ivermectin and azithromycin, key drugs in the control of neglected tropical diseases worldwide. METHODS: The entire population of Choiseul province, Solomon Islands, was eligible to participate. An azithromycin-based mass drug administration regimen was offered in line with standard recommendations for trachoma elimination (oral azithromycin or topical tetracycline). An ivermectin-based mass drug administration regimen was offered at the same time (oral ivermectin or topical permethrin), with a further dose 7-14 days later, using a modified version of a regimen demonstrated to be effective for scabies control. All participants underwent safety assessments 7-14 days later. Participants in ten randomly selected sentinel villages underwent a more detailed safety assessment. Routine health system reports of hospital or clinic admissions and deaths were also obtained to compare health outcomes in the 12 month period before and after the mass drug administration. FINDINGS: The study enrolled 26 188 participants, 99·3% of the estimated resident population as determined at the 2009 census. Of those enrolled, 25 717 (98·2%) received the trachoma regimen and 25 819 (98·6%) received the first dose of the scabies regimen between Sept 1, and Oct 2, 2015. A second dose of the scabies regimen was received by 21 931 (83·7%) of participants. Adverse events, all mild and transient, were recorded in 571 (2·6%) of the entire study population and 58 (4·1%) of participants in the ten sentinel villages. In the 12 months before and after the mass drug administration the numbers of hospital admissions (1530 vs 1602) and deaths (73 vs 83) were similar. In the month after the mass drug administration, 84 individuals were admitted to hospital and two died, compared with a monthly median of 116 admissions (IQR 106-159) and six deaths (IQR 4-7) in the 12 months before and after the mass drug administration. INTERPRETATION: In the largest trial so far involving coadministration of regimens based on ivermectin and azithromycin, the combination was safe and feasible in a population of more than 26 000 people. Coadministration of mass drug administration based on these two drugs opens up new potential for the control of neglected tropical diseases. FUNDING: International Trachoma Initiative, Murdoch Children's Research Institute, Scobie and Claire Mackinnon Trust, Wellcome Trust

Monetary Policy and Polish Labour Market in the years 1999 - 2008

This article sets out to analyse how the monetary policy pursued by the National Bank of Poland (NBP) determined the labour market situation in the country in the decade 1999-2008. The article consists of introduction as well as five sections. Section one discusses NBP's strategy of monetary policy in the defined period against monetary strategies implemented in other countries. Section two uses the growth rates of money supply and of real GDP to verify whether the primary purpose of monetary policy, i.e. the inflationary target, was achieved. Section three generally characterises the country's labour market using the levels and dynamics of employment and of unemployment. Section four discusses major instruments of NBP's monetary policy, mainly analysing changes in the central bank's interest rates and their effect on the economic situation and on the labour market. The article concludes with a summation providing synthetic conclusions.Celem artykułu jest analiza wpływu polityki monetarnej Narodowego Banku Polskiego (NBP) na sytuację na rynku pracy w Polsce w ciągu dekady obejmującej lata 1999-2008. Opracowanie składa się z wprowadzenia oraz pięciu części. W pierwszej z nich omówiona została strategia polityki monetarnej NBP w badanym okresie wraz z porównaniem ze strategią przyjmowaną w innych krajach. W części drugiej sprawdzono, czy realizowany był podstawowy cel polityki monetarnej, czyli cel inflacyjny, w kontekście kształtowania się stóp wzrostu podaży pieniądza oraz realnego PKB. W punkcie kolejnym ukazana została ogólna charakterystyka rynku pracy na podstawie kształtowania się poziomu i dynamiki zatrudnienia oraz bezrobocia. W części czwartej omówiono podstawowe instrumenty polityki pieniężnej NBP. Uwaga skoncentrowana została głównie na analizie zmian stóp procentowych banku centralnego oraz ich wpływu na sytuację gospodarczą i rynek pracy. Całość zamknięta została podsumowaniem, w którym zawarto syntetyczne wnioski końcowe

Co-axial heterostructures integrating palladium/titanium dioxide with carbon nanotubes for efficient electrocatalytic hydrogen evolution

Considering the depletion of fossil-fuel reserves and their negative environmental impact, new energy schemes must point towards alternative ecological processes. Efficient hydrogen evolution from water is one promising route towards a renewable energy economy and sustainable development. Here we show a tridimensional electrocatalytic interface, featuring a hierarchical, co-axial arrangement of a palladium/titanium dioxide layer on functionalized multi-walled carbon nanotubes. The resulting morphology leads to a merging of the conductive nanocarbon core with the active inorganic phase. A mechanistic synergy is envisioned by a cascade of catalytic events promoting water dissociation, hydride formation and hydrogen evolution. The nanohybrid exhibits a performance exceeding that of stateof- the-art electrocatalysts (turnover frequency of 15000 H2 per hour at 50mVoverpotential). The Tafel slope of B130mV per decade points to a rate-determining step comprised of water dissociation and formation of hydride. Comparative activities of the isolated components or their physical mixtures demonstrate that the good performance evolves from the synergistic hierarchical structure