Notulae to the Italian flora of algae, bryophytes, fungi and lichens: 12

In this contribution, new data concerning bryophytes, fungi and lichens of the Italian flora are presented. It includes new records, confirmations or exclusions for the bryophyte genera Acaulon, Campylopus, Entosthodon, Homomallium, Pseudohygrohypnum, and Thuidium, the fungal genera Entoloma, Cortinarius, Mycenella, Oxyporus, and Psathyrella and the lichen genera Anaptychia, Athallia, Baeomyces, Bagliettoa, Calicium, Nephroma, Pectenia, Phaeophyscia, Polyblastia, Protoparmeliopsis, Pyrenula, Ramalina, and Sanguineodiscus

Notulae to the Italian flora of algae, bryophytes, fungi and lichens: 13

In this contribution, new data concerning bryophytes, fungi and lichens of the Italian flora are presented. It includes new records and confirmations for the bryophyte genera Bryum, Cryphaea, Didymodon, and Grimmia; the fungal genera Bryostigma, Cercidospora, Conocybe, Cortinarius, Endococcus, Inocybe, Psathyrella, and Sphaerellothecium; the lichen genera Agonimia, Anisomeridium, Bilimbia, Diplotomma, Gyalecta, Huneckia, Lecidella, Lempholemma, Myriolecis, Nephroma, Pannaria, Pycnothelia, Pyrrhospora, Rinodina, Stereocaulon, Thalloidima, Trapelia, Usnea, Variospora, and Verrucaria

Multitarget Compounds for Bipolar Disorder: From Rational Design to Preliminary Pharmacokinetic Evaluation

Due to the complex and multifactorial nature of bipolar disorder (BD), single-target drugs have traditionally provided limited relief with no disease-modifying effects. In line with the polypharmacology paradigm, we attempted to overcome these limitations by devising two series of multitarget-directed ligands endowed with both a partial agonist profile at dopamine receptor D3 (D3R) and inhibitory activity against glycogen synthase kinase 3 beta (GSK-3β). These are two structurally unrelated targets that play independent, yet connected, roles in cognition and mood regulation. Two compounds (7 and 10) emerged as promising D3R/GSK-3β multitarget-directed ligands with nanomolar activity at D3R and low-micromolar inhibition of GSK-3β, thereby confirming, albeit preliminarily, the feasibility of our strategy. Furthermore, 7 showed promising drug-like properties in stability and pharmacokinetic studies

Multitarget Compounds for Bipolar Disorder: From Rational Design to Preliminary Pharmacokinetic Evaluation

Due to the complex and multifactorial nature of bipolar disorder (BD), single-target drugs have traditionally provided limited relief with no disease-modifying effects. In line with the polypharmacology paradigm, we attempted to overcome these limitations by devising two series of multitarget-directed ligands endowed with both a partial agonist profile at dopamine receptor D3 (D3R) and inhibitory activity against glycogen synthase kinase 3 beta (GSK-3β). These are two structurally unrelated targets that play independent, yet connected, roles in cognition and mood regulation. Two compounds (7 and 10) emerged as promising D3R/GSK-3β multitarget-directed ligands with nanomolar activity at D3R and low-micromolar inhibition of GSK-3β, thereby confirming, albeit preliminarily, the feasibility of our strategy. Furthermore, 7 showed promising drug-like properties in stability and pharmacokinetic studies

Retrofit Planning for the Performance Gap: Results of a Workshop on Addressing Energy, Health and Comfort Needs in a Protected Building

Research on the performance gap suggests that the actual energy consumption in buildings can be twice as much as expected from modelled estimates. Energy models rely on predictive indicators and assumptions that are usually done at the design stage, without acknowledging behavioral patterns of actual users, amongst other uncertain elements. Moreover, in the context of the performance gap, it is evident that energy efficiency is overemphasized while other key issues such as health and comfort of occupants associated with indoor air quality, noise levels etc., have been less stressed and discussed. This paper discusses physical measurements of indoor temperature in a case study building at the University of Cambridge and reports findings of a workshop with researchers, building professionals and graduate students working on environmental performance in the built environment. The workshop addressed research issues related to energy, comfort and health (couched in terms of thermal performance), used as a means to understand the complexities of and trade-off between different aspects of sustainable buildings. Retrofit measures were suggested while considering how to balance energy and comfort needs, with some these measures being modelled to determine their efficacy. This research concludes with a reflection on how to implement these retrofit measures in a manner that addresses the performance gap

Discovery and SAR Evolution of Pyrazole Azabicyclo[3.2.1]octane Sulfonamides as a Novel Class of Non-Covalent N\u2011Acylethanolamine-Hydrolyzing Acid Amidase (NAAA) Inhibitors for Oral Administration

[Image: see text] Inhibition of intracellular N-acylethanolamine-hydrolyzing acid amidase (NAAA) activity is a promising approach to manage the inflammatory response under disabling conditions. In fact, NAAA inhibition preserves endogenous palmitoylethanolamide (PEA) from degradation, thus increasing and prolonging its anti-inflammatory and analgesic efficacy at the inflamed site. In the present work, we report the identification of a potent, systemically available, novel class of NAAA inhibitors, featuring a pyrazole azabicyclo[3.2.1]octane structural core. After an initial screening campaign, a careful structure–activity relationship study led to the discovery of endo-ethoxymethyl-pyrazinyloxy-8-azabicyclo[3.2.1]octane-pyrazole sulfonamide 50 (ARN19689), which was found to inhibit human NAAA in the low nanomolar range (IC(50) = 0.042 μM) with a non-covalent mechanism of action. In light of its favorable biochemical, in vitro and in vivo drug-like profile, sulfonamide 50 could be regarded as a promising pharmacological tool to be further investigated in the field of inflammatory conditions