Pyrazolo-triazolo-pyrimidines as adenosine receptor antagonists: A complete structure–activity profile

In the last 5 years, many efforts have been conducted searching potent and selective human A3 adenosine antagonists. In this field several different classes of compounds, possessing very good affinity (nM range) and with a broad range of selectivity, have been proposed. Recently, our group synthesized a new series of pyrazolo-triazolo-pyrimidines bearing different substitutions at the N5 and N8 positions, which have been described as highly potent and selective human A3 adenosine receptor antagonists. The present review summarizes available data and provides an overview of the structure–activity relationships found for this class of human A3 adenosine receptor antagonists

Electron-phonon coupling in potassium-doped graphene: Angle-resolved photoemission spectroscopy

The electron-phonon coupling in potassium-doped graphene on Ir(111) is studied via the renormalization of the pi* band near the Fermi level, using angle-resolved photoemission spectroscopy. The renormalization is found to be fairly weak and almost isotropic, with a mass enhancement parameter of lambda= 0.28(6) for both the K-M and the K-G direction. These results are found to agree well with recent first principles calculations.Comment: 5 pages, 3 figure

Understanding decentralization: deconcentration and devolution processes in the French and Italian cultural sectors

none3noPurpose – Decentralization is a widespread and international phenomenon in public administration. Despite the interest of public management scholars, an in-depth analysis of the interrelationship between two of its forms – deconcentration and devolution – and its impact on policy and management capacities at the local level is seldom investigated. Design/methodology/approach – This article addresses this gap by examining the implementation of deconcentration and devolution processes in France and Italy in the cultural field, combining the analysis of national reform processes with in-depth analyses of two regional cases. The research is the result of document analysis, participatory observation and semi-structured interviews. Findings – The article reconstructs the impacts of devolution and deconcentration processes on the emergence of policy and management capacity in two regions (Rhone-Alpes and Piedmont) in the cultural sector. The article shows that decentralization in the cultural sector in France and Italy is the result of different combinations of devolution and deconcentration processes, that the two processes mutually affect their effectiveness, and that this effectiveness is deeply linked to the previous policy and management capacity of the central state in a specific field/country. Originality/value – The article investigates decentralization as a result of the combination of deconcentration and devolution in comparative terms and in a specific sector of implementation, highlighting the usefulness of this approach also for other sectors/countries.mixedSantagati, Maria Elena; Bonini Baraldi, Sara; Zan, LucaSantagati, Maria Elena; Bonini Baraldi, Sara; Zan, Luc

Surface Core Level Shifts of Clean and Oxygen Covered Ru(0001)

We have performed high resolution XPS experiments of the Ru(0001) surface, both clean and covered with well-defined amounts of oxygen up to 1 ML coverage. For the clean surface we detected two distinct components in the Ru 3d_{5/2} core level spectra, for which a definite assignment was made using the high resolution Angle-Scan Photoelectron Diffraction approach. For the p(2x2), p(2x1), (2x2)-3O and (1x1)-O oxygen structures we found Ru 3d_{5/2} core level peaks which are shifted up to 1 eV to higher binding energies. Very good agreement with density functional theory calculations of these Surface Core Level Shifts (SCLS) is reported. The overriding parameter for the resulting Ru SCLSs turns out to be the number of directly coordinated O atoms. Since the calculations permit the separation of initial and final state effects, our results give valuable information for the understanding of bonding and screening at the surface, otherwise not accessible in the measurement of the core level energies alone.Comment: 16 pages including 10 figures. Submitted to Phys. Rev. B. Related publications can be found at http://www.fhi-berlin.mpg.de/th/paper.htm

N-{3-[Bis(2-hydroxy­ethyl)amino­meth­yl]-5-nitro­phen­yl}benzamide

The title compound, C18H21N3O5, was prepared by the reaction of 3-benzamido-5-nitro­benzyl methane­sulfonate with diethano­lamine and is an inter­mediate in the synthesis of DNA minor-groove-binding polybenzamide agents capable of being conjugated to additional biologically active species. The asymmetric unit contains two independent mol­ecules, which differ only in the orientations of the hydroxy­ethyl groups. In the crystal structure, inter­molecular N—H⋯O and O—H⋯O hydrogen bonds link mol­ecules into one-dimensional chains

OnabotulinumtoxinA: Still the Present for Chronic Migraine

OnabotulinumtoxinA (BT-A) is one of the few drugs approved for the preventive treatment of chronic migraine (CM). Despite this, some aspects of its mechanism of action are still a matter of debate, and the precise magnitude of BT-A effects needs to be completely elucidated. BT-A acts primarily upon trigeminal and cervical nerve endings, by inhibiting the release of inflammatory mediators such as calcitonin gene-related peptide, as well as reducing the insertion of ionotropic and metabotropic receptors into the neuronal membrane. These actions increase the depolarization threshold of trigeminal and cervical nerve fibers, thus reducing their activation. The central actions of BT-A are still a matter of debate: a retrograde axonal transport has been postulated, but not clearly assessed in humans. Clinically, the efficacy of BT-A in CM has been assessed by large, randomized placebo-controlled trials, such as the Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) trials. Those results were also confirmed in a wide range of open-label studies, even for long-term periods. Recently, novel findings have led to a better understanding of its pharmacological actions and clinical usefulness in migraine prevention. This narrative review summarizes, updates and critically revises the available data on BT-A and its possible implementation in chronic migraine. Moreover, the current role of BT-A in CM treatment has been discussed

Role of xanthophyll cycle-mediated photoprotection in Arbutus unedo plants exposed to water stress during the Mediterranean summer

We analyzed the response of potted strawberry tree (Arbutus unedo L.) seedlings exposed to water stress by withholding water for 10 d (WS). Leaf water potential, net CO2 assimilation, and stomatal conductance decreased with increasing water deficit. A 30 % reduction of chlorophyll (Chl) content in the antenna complexes was observed in WS-plants. Simultaneously, a decline of photochemical efficiency (F-v/F-m) occurred as a result of an excess of solar radiation energy when carbon assimilation was limited by stomata closure due to soil water deficit. The non-photochemical quenching of Chl fluorescence (Phi(NPQ)) significantly increased, as well as the leaf contents of zeaxanthin (Z) and antheraxanthin (A) at the expense of violaxanthin during the WS-period. Elevated predawn contents of de-epoxidized xanthophyll cycle components were associated with a sustained lowering of predawn photosystem 2 efficiency; this suggested an engagement of Z+A in a state primed for energy dissipation. Thus, the ability of strawberry trees to maintain the functionality of the xanthophyll cycle during the Mediterranean summer is an efficient mechanism to prevent irreversible damages to the photosynthetic machinery through thermal energy dissipation in the antenna and the reduction in photochemical efficiency

Predictors of response to erenumab after 12 months of treatment

Objective: Erenumab is a monoclonal antibody acting against calcitonin gene-related peptide receptor and approved for the preventive treatment of chronic migraine. The aim of the present study is to identify clinical predictors of good response in patients with chronic migraine and medication overuse-headache. Material and methods: This was a retrospective single-center not funded study. Enrolled patients were affected by chronic migraine and medication overuse-headache treated with erenumab monthly, up to 1 year. At 1 year, patients were classified as good responders if they displayed a ≥50% reduction in the number of headache days per months compared to the baseline. Results: After 1 year, a significant improvement in the number of headache days per months, analgesic consumption, 6-items headache impact test, and migraine disability assessment questionnaire scores were obtained compared to the baseline. Patients who obtained a ≥50% reduction in the number of headache days per month compared to the baseline displayed a longer history of medication overuse-headache, a higher number of painkillers taken per month at the baseline and a higher number of failed preventive treatments in the past. Conclusions: Patients with longer medication overuse-headache duration, higher analgesic intake, and a higher number of previous preventive treatment failures may receive less benefit with erenumab

Effects of pidotimod and bifidobacteria mixture on clinical symptoms and urinary metabolomic profile of children with recurrent respiratory infections: a randomized placebo-controlled trial

Many preschool children develop recurrent respiratory tract infections (RRI). Strategies to prevent RRI include the use of immunomodulators as pidotimod or probiotics, but there is limited evidence of their efficacy on clinical features or on urine metabolic profile