Genes and miRNAs as Hurdles and Promoters of Corticospinal Tract Regeneration in Spinal Cord Injury

Spinal cord injury (SCI) is a devastating lesion to the spinal cord, which determines the interruption of ascending/descending axonal tracts, the loss of supraspinal control of sensory-motor functions below the injured site, and severe autonomic dysfunctions, dramatically impacting the quality of life of the patients. After the acute inflammatory phase, the progressive formation of the astrocytic glial scar characterizes the acute-chronic phase: such scar represents one of the main obstacles to the axonal regeneration that, as known, is very limited in the central nervous system (CNS). Unfortunately, a cure for SCI is still lacking: the current clinical approaches are mainly based on early vertebral column stabilization, anti-inflammatory drug administration, and rehabilitation programs. However, new experimental therapeutic strategies are under investigation, one of which is to stimulate axonal regrowth and bypass the glial scar. One major issue in axonal regrowth consists of the different genetic programs, which characterize axonal development and maturation. Here, we will review the main hurdles that in adulthood limit axonal regeneration after SCI, describing the key genes, transcription factors, and miRNAs involved in these processes (seen their reciprocal influencing action), with particular attention to corticospinal motor neurons located in the sensory-motor cortex and subjected to axotomy in case of SCI. We will highlight the functional complexity of the neural regeneration programs. We will also discuss if specific axon growth programs, that undergo a physiological downregulation during CNS development, could be reactivated after a spinal cord trauma to sustain regrowth, representing a new potential therapeutic approach

Analysis of navigation pattern in the sport of rowing

The effect of weather and environmental conditions on sports has been extensively studied over the last few years (Pezzoli et al., 2010). Based upon the studies of Lobozewicz (1981) and of Kay and Vamplew (2002), Pezzoli and Cristofori (2008) have studied the impact of some specific environmental parameters over different sports using a particular impact index divided into five classes. This analysis clearly shows that most of the outdoor sport activities are strongly influenced by the variation of meteorological parameters. However the impact of meteorological conditions on outdoor sport activities has not yet been extensively studied. The aim of this research is to show that an accurate assessment of wind and wave parameters enables decisive improvements in both training and race strategy planning. Furthermore this analysis provide a very innovative working method for the applied sport research. The work has been based on in-situ measurements of both environmental and performance parameters (wind direction, wind velocity, boat speed and stroke rate) made over different classes and in different race conditions during the 2009 FISA World Championship (Poznan, Poland). In particular a detailed environmental analysis was performed by measuring the wind direction, the wind speed and by evaluating the significant wave height and the wave peak period for each class during the semi-final phase and the final phase. It should be noted that, since wind is a key parameter affecting not only the boat speed but also the race strategy, the assessment of the wind velocity and of the wind direction has been made in connection with the boat movement. The comparison between coupled wind-wave data, boat speed and stroke rate evidently demonstrates that only crews that managed the adaption to changing in the environmental conditions from semi-final to final phase of the race, were able to get better results. References Kay, J., & Vamplew, W. (2002) Weather beaten: sport in the British climate. London: Ed. Mainstream Publishing. Lobozewicz, T. (1981) Meteorology in sport. Frankfurt: Ed. Sportverlag. Pezzoli, A,, Moncalero, M., Boscolo, A., Cristofori, E., Giacometto, F., Gastaldi, S., & Vercelli, G. (2010) The meteo-hydrological analysis and the sport performance: which are the connections? The case of the XXI Winter Olympic Games, Vancouver 2010, Journal of Sports Medicine and Physical Fitness, 50: 19-20. Pezzoli, A., & Cristofori, E. (2008) Analisi, previsioni e misure meteorologiche applicate agli sport equestri, in: 10th Congress "New findings in equine practices, Druento: Centro Internazionale del Cavallo Ed., p.38-4

Increasing agrin function antagonizes muscle atrophy and motor impairment in spinal muscular atrophy

Spinal muscular atrophy (SMA) is a pediatric genetic disease, characterized by motor neuron (MN) death, leading to progressive muscle weakness, respiratory failure, and, in the most severe cases, to death. Abnormalities at the neuromuscular junction (NMJ) have been reported in SMA, including neurofilament (NF) accumulation at presynaptic terminals, immature and smaller than normal endplates, reduced transmitter release, and, finally, muscle denervation. Here we have studied the role of agrin in SMAΔ7 mice, the experimental model of SMAII. We observed a 50% reduction in agrin expression levels in quadriceps of P10 SMA mice compared to age-matched WT controls. To counteract such condition, we treated SMA mice from birth onwards with therapeutic agrin biological NT-1654, an active splice variant of agrin retaining synaptogenic properties, which is also resistant to proteolytic cleavage by neurotrypsin. Mice were analyzed for behavior, muscle and NMJ histology, and survival. Motor behavior was significantly improved and survival was extended by treatment of SMA mice with NT-1654. At P10, H/E-stained sections of the quadriceps, a proximal muscle early involved in SMA, showed that NT-1654 treatment strongly prevented the size decrease of muscle fibers. Studies of NMJ morphology on whole-mount diaphragm preparations revealed that NT-1654-treated SMA mice had more mature NMJs and reduced NF accumulation, compared to vehicle-treated SMA mice. We conclude that increasing agrin function in SMA has beneficial outcomes on muscle fibers and NMJs as the agrin biological NT-1654 restores the crosstalk between muscle and MNs, delaying muscular atrophy, improving motor performance and extending survival

Enabling onshore CO2 storage in Europe: fostering international cooperation around pilot and test sites

To meet the ambitious EC target of an 80% reduction in greenhouse gas emissions by 2050, CO2 Capture and Storage (CCS) needs to move rapidly towards full scale implementation with geological storage solutions both on and offshore. Onshore storage offers increased flexibility and reduced infrastructure and monitoring costs. Enabling onshore storage will support management of decarbonisation strategies at territory level while enhancing security of energy supply and local economic activities, and securing jobs across Europe. However, successful onshore storage also requires overcoming some unique technical and societal challenges. ENOS will provide crucial advances to help foster onshore CO2 storage across Europe through: 1. Developing, testing and demonstrating in the field, under "real-life conditions", key technologies specifically adapted to onshore storage. 2. Contributing to the creation of a favourable environment for onshore storage across Europe. The ENOS site portfolio will provide a great opportunity for demonstration of technologies for safe and environmentally sound storage at relevant scale. Best practices will be developed using experience gained from the field experiments with the participation of local stakeholders and the lay public. This will produce improved integrated research outcomes and increase stakeholder understanding and confidence in CO2 storage. In this improved framework, ENOS will catalyse new onshore pilot and demonstration projects in new locations and geological settings across Europe, taking into account the site-specific and local socio-economic context. By developing technologies from TRL4/5 to TRL6 across the storage lifecycle, feeding the resultant knowledge and experience into training and education and cooperating at the pan-European and global level, ENOS will have a decisive impact on innovation and build the confidence needed for enabling onshore CO2 storage in Europe. ENOS is initiating strong international collaboration between European researchers and their counterparts from the USA, Canada, South Korea, Australia and South Africa for sharing experience worldwide based on real-life onshore pilots and field experiments. Fostering experience-sharing and research alignment between existing sites is key to maximise the investment made at individual sites and to support the efficient large scale deployment of CCS. ENOS is striving to promote collaboration between sites in the world through a programme of site twinning, focus groups centered around operative issues and the creation of a leakage simulation alliance

Mesenchymal Stem Cells for Spinal Cord Injury: Current Options, Limitations, and Future of Cell Therapy

Spinal cord injury (SCI) constitutes an inestimable public health issue. The most crucial phase in the pathophysiological process of SCI concerns the well-known secondary injury, which is the uncontrolled and destructive cascade occurring later with aberrant molecular signaling, inflammation, vascular changes, and secondary cellular dysfunctions. The use of mesenchymal stem cells (MSCs) represents one of the most important and promising tested strategies. Their appeal, among the other sources and types of stem cells, increased because of their ease of isolation/preservation and their properties. Nevertheless, encouraging promise from preclinical studies was followed by weak and conflicting results in clinical trials. In this review, the therapeutic role of MSCs is discussed, together with their properties, application, limitations, and future perspectives