Bone Marrow-Mesenchymal Stromal Cell Secretome as Conditioned Medium Relieves Experimental Skeletal Muscle Damage Induced by Ex Vivo Eccentric Contraction

Bone marrow-mesenchymal stem/stromal cells (MSCs) may offer promise for skeletal muscle repair/regeneration. Growing evidence suggests that the mechanisms underpinning the beneficial effects of such cells in muscle tissue reside in their ability to secrete bioactive molecules (secretome) with multiple actions. Hence, we examined the effects of MSC secretome as conditioned medium (MSC-CM) on ex vivo murine extensor digitorum longus muscle injured by forced eccentric contraction (EC). By combining morphological (light and confocal laser scanning microscopies) and electrophysiological analyses we demonstrated the capability of MSC-CM to attenuate EC-induced tissue structural damages and sarcolemnic functional properties’ modifications. MSC-CM was effective in protecting myofibers from apoptosis, as suggested by a reduced expression of pro-apoptotic markers, cytochrome c and activated caspase-3, along with an increase in the expression of pro-survival AKT factor. Notably, MSC-CM also reduced the EC-induced tissue redistribution and extension of telocytes/CD34⁺ stromal cells, distinctive cells proposed to play a “nursing” role for the muscle resident myogenic satellite cells (SCs), regarded as the main players of regeneration. Moreover, it affected SC functionality likely contributing to replenishment of the SC reservoir. This study provides the necessary groundwork for further investigation of the effects of MSC secretome in the setting of skeletal muscle injury and regenerative medicine.     

Guessing Bank PINs by Winning a Mastermind Game

In this paper we formally prove that the problem of cracking, i.e., correctly guessing, bank PINs used for accessing Automated Teller Machines and the problem of solving the Generalized Mastermind Game are strictly related. The Generalized Mastermind Game with N colors and k pegs is an extension of the well known Mastermind game, played with 6 colors and 4 pegs. The rules are the same, one player has to conceal a sequence of k colored pegs behind a screen and another player has to guess the exact position and colors of the pegs using the minimal number of moves. We first introduce a general game, called the Extended Mastermind Game (EMG), and we then formally prove it includes both the Generalized Mastermind Game and the PIN cracking Problem. We then present some experimental results that we have devised using a computer program that optimizes a well known technique presented by Knuth in 1976 for the standard Mastermind game. We finally show that the program improves the as state-of-the-art Mastermind solvers as it is able to compute strategies for cases which were not yet covered. More interestingly, the same solving strategy is adapted also for the solution of the PIN cracking problem.     

Chiral recognition by mass-resolved laser spectroscopy

Chiral recognition is a fundamental phenomenon in life sciences, based on the enantioselective complexation of a chiral molecule with a chiral selector. The diastereomeric aggregates, formed by complexation, are held together by a different combination of intermolecular forces and are therefore endowed with different stability and reactivity. Determination of these forces, which are normally affected in the condensed phase by solvent and supramolecular interactions, requires the generation of the diastereomeric complexes in the isolated state and their spectroscopic investigation. This review deals with chiral recognition in the gas phase through the application of laser-resolved mass spectrometric techniques (R2PI-TOF and RET-MS). The measurement of the fragmentation thresholds of diastereomeric clusters by these techniques allows the determination of the nature of the intrinsic interactions, which control their formation and affect their stability and reactivity.     

Routing in Series Parallel Networks

Abstract. We consider the problem of routing messages between pairs of nodes of a distributed network, along shortest paths. We introduce a new routing technique, called Distance Routing that, due to its structure, is naturally well applicable on a family of networks called Series Parallel Graphs. We compute the time and space complexities of Distance Routing in Series Parallel Graphs, and we compare them with the relative complexities of Interval Routing, showing the improvement of Distance Routing especially in terms of time complexity.     

Fault-Tolerant Support for Reliable Multicast in Mobile Wireless Systems: Design and Evaluation

In this paper we present a protocol for reliable multicast within a group of mobile hosts that communicate with a wired infrastructure by means of wireless technology. The protocol assumes that the wireless coverage may be incomplete and message losses could occur even within cells, due to physical obstructions or to the high error rate of the wireless technology, for example. A novel feature of our proposal is that it tolerates failures in the wired infrastructure, i.e., crashes of stationary hosts and partitions of wired links. In particular, upon such failures mobile hosts simply observe that the covered area has shrunk. The covered area will enlarge back to its original extension when the failure recovers. We evaluate our protocol by means of an extensive simulation analysis. The main findings of our analysis are: the protocol exhibits very good scalability properties; the performance degradation induced by fault-tolerance is moderate.     

Benzene exposure in a sample of population residing in a district of Florence, Italy

OBJECTIVE: Personal exposure to airborne benzene is influenced by various outdoor and indoor sources. The first aim of this study was to assess the benzene exposure of a sample of urban inhabitants living in an inner-city neighborhood of Florence, Italy, excluding exposure from active smoking. The secondary objective was to differentiate the personal exposures according to personal usage patterns of the vehicles. METHODS: A sample of 67 healthy non-smokers was monitored by passive samplers during two 4-weekday campaigns in winter and late spring. Simultaneously, benzene measurements were also taken for a subset of participants, inside and outside their houses. A 4-day time microenvironment activity diary was completed by each subject during each sampling period. Other relevant exposure data were collected by a questionnaire before the sampling. Additional data on urban ambient air benzene levels were also available from the public air quality network. The passive samplers, after automated thermal desorption, were analyzed by GC-FID. RESULTS: Benzene personal exposure levels averaged 6.9 (SD=2.1) and 2.3 (SD=0.7) microg/m(3) in winter and spring, respectively. Outdoor and indoor levels showed high correlation in winter and poor in spring. In winter the highest benzene personal exposure levels were for people traveling by more public transport, followed by users of only car and by users of only bus respectively. CONCLUSIONS: The time spent in-transport for work or leisure makes a major contribution to benzene exposure among Florentine non-smoking citizens. Indoor pollution and transportation means contribute significantly to individual exposure levels especially in winter season.     

Dose- and strain-dependent effects of dermorphin and [D-Ala–2-D-Leu–5]enkephalin on passive avoidance behavior in mice.

Dermorphin and dextro-ala–2-dextro-leu–5-enkephalin, administered intracerebroventricularly (icv) immediately after training in a passive avoidance test, exerted dose- and strain-dependent effects in DBA/2 and C57BL/6 mice. The peptides impaired, at a low dose (5 ng), the retention performances of both strains; a higher dose (50 ng) impaired retention in DBA/2 mice but improved it in C57BL/6 mice. A dose of naloxone (0.3 μg, icv), which was ineffective when administered alone, antagonized the effects observed. (42 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Turning Donepezil into a Multi-Target-Directed Ligand through a Merging Strategy

Thanks to the widespread use and safety profile of donepezil ( 1 ) in the treatment of Alzheimer's disease (AD), one of the most widely adopted multi-target-directed ligand (MTDL) design strategies is to modify its molecular structure by linking a second fragment carrying an additional AD-relevant biological property. Herein, supported by a proposed combination therapy of 1 and the quinone drug idebenone, we rationally designed novel 1 -based MTDLs targeting Aβ and oxidative pathways. By exploiting a bioisosteric replacement of the indanone core of 1 with a 1,4-naphthoquinone, we ended up with a series of highly merged derivatives, in principle devoid of the “physicochemical challenge” typical of large hybrid-based MTDLs. A preliminary investigation of their multi-target profile identified 9 , which showed a potent and selective butyrylcholinesterase inhibitory activity, together with antioxidant and antiaggregating properties. In addition, it displayed a promising drug-like profile.