Perspectives on hiPSC-Derived Muscle Cells as Drug Discovery Models for Muscular Dystrophies

Muscular dystrophies are a heterogeneous group of inherited diseases characterized by the progressive degeneration and weakness of skeletal muscles, leading to disability and, often, premature death. To date, no effective therapies are available to halt or reverse the pathogenic process, and meaningful treatments are urgently needed. From this perspective, it is particularly important to establish reliable in vitro models of human muscle that allow the recapitulation of disease features as well as the screening of genetic and pharmacological therapies. We herein review and discuss advances in the development of in vitro muscle models obtained from human induced pluripotent stem cells, which appear to be capable of reproducing the lack of myofiber proteins as well as other specific pathological hallmarks, such as inflammation, fibrosis, and reduced muscle regenerative potential. In addition, these platforms have been used to assess genetic correction strategies such as gene silencing, gene transfer and genome editing with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), as well as to evaluate novel small molecules aimed at ameliorating muscle degeneration. Furthermore, we discuss the challenges related to in vitro drug testing and provide a critical view of potential therapeutic developments to foster the future clinical translation of preclinical muscular dystrophy studies.     

Reduced nitric oxide synthase and cyclo-oxygenase activity in the uterus of non-obese diabetic mice

A functional interaction between progesterone, Th2 cytokines and a suitable balance between nitric oxide and prostaglandins in the uterus is considered to have a major role in the success of embryo implantation and pregnancy. Non-obese diabetic (NOD) mice offer a suitable model to study the modulatory role of Th1 cytokines on uterus signalling and function, since at the prediabetic stage they develop a spontaneous Th1 autoimmune response against exocrine glands similar to Sj?gren's syndrome. Vasoactive intestinal peptide (VIP) is a vasoactive neuro- and immunopeptide that promotes Th2 profiles and contributes to the smooth muscle relaxation and vasodilation. The aim of the present study was to investigate the activities of nitric oxide synthase and cyclo-oxygenase and the effect of VIP in the uterus of NOD mice with an emerging Th1 cytokine response. We present evidence of a reduced basal and VIP-stimulated activity of both enzymes in the uterus of NOD mice compared with normal BALB/c mice in proestrus. An altered functional interaction between both enzymes is also present in NOD mice at the time when increased levels of serum interleukin (IL)-12 and tumour necrosis factor-alpha but not interferon (IFN)-gamma or IL-10 were detected. We conclude that signalling alterations in uteri of NOD mice are simultaneous to the onset of a systemic Th1 cytokine response.     

On the proton conductivity of Nafion-Faujasite composite membranes for low temperature direct methanol fuel cells

Although zeolites are introduced to decrease methanol crossover of Nafion membranes for direct methanol fuel cells (DMFCs), little is known about the effect of their intrinsic properties and the interaction with the ionomer. In this work, Nafion-Faujasite composite membranes prepared by solution casting were characterized by extensive physicochemical and electrochemical techniques. Faujasite was found to undergo severe dealumination during the membrane activation, but its structure remained intact. The zeolite interacts with Nafion probably through hydrogen bonding between Si-OH and SO₃H groups, which combined with the increase of the water uptake and the water mobility, and the addition of a less conductive phase (the zeolite) leads to an optimum proton conductivity between 0.98 and 2 wt% of zeolite. Hot pressing the membranes before their assembling with the electrodes enhanced the DMFC performance by reducing the methanol crossover and the serial resistance.     

Carbon nanotubes/polydimethylsiloxanes systems for thermal management of miniaturized electronic components

The thermal performances of nanocomposite layers formed by Single-walled Carbon Nanotubes (SWCNT) dispersed in 2 different kind of polydimethyl-siloxane (PDMSO) matrices has been investigated by measuring the thermal resistance under conditions similar to the ones used for thermal management in microelectronics. A series of nanocomposite samples with thickness in the range 25 microm(-1) cm have been tested. The nanocomposites were prepared varying the amounts of nanotubes embedded in the matrix (from 0.1 to 5%w). In some cases also microsized graphites were mixed to the nanotube's fillers. For 25 micron thick layers, the thermal resistance of the neat silicone specimen can be reduced of 54% with the addition of 2%w carbon nanotubes. The variation of thermal conductivity as a function of the SWCNT's loading is reported and discussed. Furthermore the dispersion's effects of the nanotubes in the layers and the effects on the realization of a net-like system have been investigated.     

New insights on the consolidation of salt weathered limestone: the case study of Modica stone

Bulletin of Engineering Geology and the Environment - The deterioration of a stone material is related to its pore structure, which affects the interaction between surface and environmental agents....