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Amyotrophic lateral sclerosis (ALS) is a fatal, progressive paralysis arising from the premature death of motor neurons. An inherited form is caused by a dominant mutation in the ubiquitously expressed superoxide dismutase (SOD1). SOD1 mutant expression within motor neurons is a determinant of onset and early disease, and mutant accumulation within microglia accelerates disease progression. Muscle also is a likely primary source for toxicity, because retraction of motor axons from synaptic connections to muscle is among the earliest presymptomatic events. To test involvement of muscle in ALS, viral delivery of transcriptionmediated siRNA is shown to suppress mutant SOD1 accumulation within muscle alone but to be insufficient to maintain grip strength, whereas delivery to both motor neurons and muscle is sufficient. Use of a deletable mutant gene to diminish mutant SOD1 from muscle did not affect onset or survival. Finally, follistatin expression encoded by adeno-associated virus chronically inhibited myostatin and produced sustained increases in muscle mass, myofiber number, and fiber diameter, but these increases did not affect survival. Thus, SOD1-mutant-mediated damage within muscles is not a significant contributor to non-cell-autonomous pathogenesis in ALS, and enhancing muscle mass and strength provides no benefit in slowing disease onset or progression.siRNA ͉ adeno-associated virus ͉ motor neuron ͉ G93A SOD1 ͉ myostatin

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the motor system. Recent work in rodent models of ALS has shown that insulin-like growth factor-1 (IGF-1) slows disease progression when delivered at disease onset. However, IGF-1's mechanism of action along the neuromuscular axis remains unclear. In this study, symptomatic ALS mice received IGF-1 through stereotaxic injection of an IGF-1-expressing viral vector to the deep cerebellar nuclei (DCN), a region of the cerebellum with extensive brain stem and spinal cord connections. We found that delivery of IGF-1 to the central nervous system (CNS) reduced ALS neuropathology, improved muscle strength, and significantly extended life span in ALS mice. To explore the mechanism of action of IGF-1, we used a newly developed in vitro model of ALS. We demonstrate that IGF-1 is potently neuroprotective and attenuates glial cell-mediated release of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO). Our results show that delivering IGF-1 to the CNS is sufficient to delay disease progression in a mouse model of familial ALS and demonstrate for the first time that IGF-1 attenuates the pathological activity of non-neuronal cells that contribute to disease progression. Our findings highlight an innovative approach for delivering IGF-1 to the CNS.

dimensional pore structure of SBA-1, which limits pore blocking and allows a faster diffusion of the reactant molecules.In conclusion, our results reveal that Fe has been successfully incorporated, for the first time, into SBA-1 by simply adjusting the molar hydrochloric acid to surfactant ratio. UVvis DRS and ESR studies confirm that the majority of the Fe atoms in FeSBA-1 exist in a tetrahedral coordination environment (most probably occupying framework positions). The catalytic activity of the novel catalyst was investigated in the vapor phase tert-butylation of phenol reaction. FeSBA-1(36) was found to be more active than previously studied systems such as FeAlMCM-41 or sulfated zirconica. The observed phenol conversion of 78.8 % (S 4-TBP = 70 %) is significantly higher as compared to other mono-and bimetal substituted uni-dimensional MCM-41 molecular sieves under optimized reaction conditions. [13,17] Experimental Iron containing SBA-1 was synthesized under acidic conditions using cetyltriethylammonium bromide (CTEABr) as the surfactant, tetraethylorthosilicate (TEOS) as the silica source and ferric nitrate nonahydrate as the iron source. The surfactant (CTEABr) was synthesized by the reaction of 1-bromohexadecane with an equimolar amount of triethylamine in ethanol under reflux conditions for two days. The resulting solid CTEABr was purified via recrystallization from a chloroform/ethyl acetate mixture. A typical synthesis procedure for FeSBA-1 is as follows: Solution A was prepared by adding 0.812 g of CTEABr to an appropriate amount of the aqueous solution of 4.4 M HCl (n HCl /n H 2 O ratio was fixed to 0.08). The solution thus obtained was cooled to 0 C and homogenized for 30 min. TEOS and Fe(NO 3 ) 3´9 H 2 O were precooled to 0 C and then added to solution A under vigorous stirring and continued the stirring for another 5 h at 0 C. Thereafter, the reaction mixture was heated to 100 C for 1 h. The samples were labeled FeSBA-1(x) where x denotes the n Si /n Fe molar ratio. The solid product was recovered by filtration and dried in an oven at 100 C overnight. The molar composition of the gel was 1 TEOS:0.0025±0.025 Fe 2 O 3 :0.2 CTEABr:10±56 HCl:125±700 H 2 O. The as-synthesized material was then calcined in air by raising the temperature from 20 to 550 C with a heating rate of 1.8 Cmin ±1 and keeping the sample at the final temperature for 10 h. Energetic materials are classified as those that convert chemical enthalpy to thermal enthalpy rapidly. They are commonly used in explosives, propulsion, and pyrotechnics. The synthesis of nanostructured energetic materials has recently drawn considerable attention as a potential method that can be used to obtain energy release more rapidly than conventional materials. It is known that the size distribution and the degree of intermixing of thermite-like reactants (e.g., metal/ metal oxide) significantly affects the burning rate of energetic materials. For instance, nanoparticles of fuel/oxidizer materials have been reported to have burning rates~1000 times high...