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This article is from International Journal of Molecular Sciences , volume 13 . Abstract Motor neurons typically have very long axons, and fine-tuning axonal transport is crucial for their survival. The obstruction of axonal transport is gaining attention as a cause of neuronal dysfunction in a variety of neurodegenerative motor neuron diseases. Depletions in dynein and dynactin-1, motor molecules regulating axonal trafficking, disrupt axonal transport in flies, and mutations in their genes cause motor neuron degeneration in humans and rodents. Axonal transport defects are among the early molecular events leading to neurodegeneration in mouse models of amyotrophic lateral sclerosis (ALS). Gene expression profiles indicate that dynactin-1 mRNA is downregulated in degenerating spinal motor neurons of autopsied patients with sporadic ALS. Dynactin-1 mRNA is also reduced in the affected neurons of a mouse model of spinal and bulbar muscular atrophy, a motor neuron disease caused by triplet CAG repeat expansion in the gene encoding the androgen receptor. Pathogenic androgen receptor proteins also inhibit kinesin-1 microtubule-binding activity and disrupt anterograde axonal transport by activating c-Jun N-terminal kinase. Disruption of axonal transport also underlies the pathogenesis of spinal muscular atrophy and hereditary spastic paraplegias. These observations suggest that the impairment of axonal transport is a key event in the pathological processes of motor neuron degeneration and an important target of therapy development for motor neuron diseases.

This article is from International Journal of Molecular Sciences , volume 13 . Abstract Motor neurons typically have very long axons, and fine-tuning axonal transport is crucial for their survival. The obstruction of axonal transport is gaining attention as a cause of neuronal dysfunction in a variety of neurodegenerative motor neuron diseases. Depletions in dynein and dynactin-1, motor molecules regulating axonal trafficking, disrupt axonal transport in flies, and mutations in their genes cause motor neuron degeneration in humans and rodents. Axonal transport defects are among the early molecular events leading to neurodegeneration in mouse models of amyotrophic lateral sclerosis (ALS). Gene expression profiles indicate that dynactin-1 mRNA is downregulated in degenerating spinal motor neurons of autopsied patients with sporadic ALS. Dynactin-1 mRNA is also reduced in the affected neurons of a mouse model of spinal and bulbar muscular atrophy, a motor neuron disease caused by triplet CAG repeat expansion in the gene encoding the androgen receptor. Pathogenic androgen receptor proteins also inhibit kinesin-1 microtubule-binding activity and disrupt anterograde axonal transport by activating c-Jun N-terminal kinase. Disruption of axonal transport also underlies the pathogenesis of spinal muscular atrophy and hereditary spastic paraplegias. These observations suggest that the impairment of axonal transport is a key event in the pathological processes of motor neuron degeneration and an important target of therapy development for motor neuron diseases.

This article is from Frontiers in Physiology , volume 4 . Abstract Spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), and spinal-bulbar muscular atrophy (SBMA) are devastating diseases characterized by the degeneration of motor neurons. Although the molecular causes underlying these diseases differ, recent findings have highlighted the contribution of intrinsic skeletal muscle defects in motor neuron diseases. The use of cell culture and animal models has led to the important finding that muscle defects occur prior to and independently of motor neuron degeneration in motor neuron diseases. In SMA for instance, the muscle specific requirements of the SMA disease-causing gene have been demonstrated by a series of genetic rescue experiments in SMA models. Conditional ALS mouse models expressing a muscle specific mutant SOD1 gene develop atrophy and muscle degeneration in the absence of motor neuron pathology. Treating SBMA mice by over-expressing IGF-1 in a skeletal muscle-specific manner attenuates disease severity and improves motor neuron pathology. In the present review, we provide an in depth description of muscle intrinsic defects, and discuss how they impact muscle function in these diseases. Furthermore, we discuss muscle-specific therapeutic strategies used to treat animal models of SMA, ALS, and SBMA. The study of intrinsic skeletal muscle defects is crucial for the understanding of the pathophysiology of these diseases and will open new therapeutic options for the treatment of motor neuron diseases.

This article is from Frontiers in Cellular Neuroscience , volume 8 . Abstract Motor neuron diseases (MNDs) are characterized by selective death of motor neurons and include mainly adult-onset amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). Neurodegeneration is not the single pathogenic event occurring during disease progression. There are multiple lines of evidence for the existence of defects in lipid metabolism at peripheral level. For instance, hypermetabolism is well characterized in ALS, and dyslipidemia correlates with better prognosis in patients. Lipid metabolism plays also a role in other MNDs. In SMA, misuse of lipids as energetic nutrients is described in patients and in related animal models. The composition of structural lipids in the central nervous system is modified, with repercussion on membrane fluidity and on cell signaling mediated by bioactive lipids. Here, we review the main epidemiologic and mechanistic findings that link alterations of lipid metabolism and motor neuron degeneration, and we discuss the rationale of targeting these modifications for therapeutic management of MNDs.

This article is from Frontiers in Cellular Neuroscience , volume 8 . Abstract Motor neuron diseases (MNDs) are characterized by selective death of motor neurons and include mainly adult-onset amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). Neurodegeneration is not the single pathogenic event occurring during disease progression. There are multiple lines of evidence for the existence of defects in lipid metabolism at peripheral level. For instance, hypermetabolism is well characterized in ALS, and dyslipidemia correlates with better prognosis in patients. Lipid metabolism plays also a role in other MNDs. In SMA, misuse of lipids as energetic nutrients is described in patients and in related animal models. The composition of structural lipids in the central nervous system is modified, with repercussion on membrane fluidity and on cell signaling mediated by bioactive lipids. Here, we review the main epidemiologic and mechanistic findings that link alterations of lipid metabolism and motor neuron degeneration, and we discuss the rationale of targeting these modifications for therapeutic management of MNDs.

This article is from Frontiers in Cellular Neuroscience , volume 8 . Abstract Motor neuron diseases (MNDs) are characterized by selective death of motor neurons and include mainly adult-onset amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). Neurodegeneration is not the single pathogenic event occurring during disease progression. There are multiple lines of evidence for the existence of defects in lipid metabolism at peripheral level. For instance, hypermetabolism is well characterized in ALS, and dyslipidemia correlates with better prognosis in patients. Lipid metabolism plays also a role in other MNDs. In SMA, misuse of lipids as energetic nutrients is described in patients and in related animal models. The composition of structural lipids in the central nervous system is modified, with repercussion on membrane fluidity and on cell signaling mediated by bioactive lipids. Here, we review the main epidemiologic and mechanistic findings that link alterations of lipid metabolism and motor neuron degeneration, and we discuss the rationale of targeting these modifications for therapeutic management of MNDs.

1Seven Little Australians

By Ethel Turner

This is the story of seven incorrigible children living near Sydney in the 1880’s with their military-man father, and a stepmother who is scarcely older than the oldest child of the family. A favourite amongst generations of children for over a century, this story tells of the cheeky exploits of Meg, Pip, Judy, Bunty, Nell, Baby, and The General (who is the real baby of the family), as well as providing a fascinating insight into Australian family life in a bygone era. (Summary by Ophelia Darcy)

2Van Dyck

By Percy M. Turner

A biography and critique of Van Dyck in The Masterpieces in Colour series. The Plates of the paintings are fully described and the artistic periods in his life's work are given as well as his place in history. (Summary by Susan Morin)

3Frontier in American History

By Frederick Jackson Turner

Frederick Jackson Turner was an extremely influential U.S. historian, who is best known for his "frontier thesis", which proposed that American democracy was profoundly shaped by the existence of an undeveloped frontier area from the founding through the 1880s. He originally put forth his idea in the essay "The Significance of the Frontier in American History", published just three years after the frontier was "officially closed" in 1890. He continued to elaborate on the frontier thesis as well as the influence of sectionalism, and the unique contributions of the Midwest to American democracy. His theory and other writings are still debated by modern day historians. This work, The Frontier in American History, collects a number of Turner's essays and speeches, including "The Significance of the Frontier in American History."

LibriVox volunteers bring you ten recordings of "A Summer Night in the Beehive." The Weekly Poem for August 24, 2014 brings us the night sounds of the meadow in summer.

5High Hander

By William Oliver Turner

Tesno was a troubleshooter. That's why the railroad construction company had hired him. His job was to make sure that nobody interfered with the tunnel that they were digging through that frontier region mountain. Tesno knew one thing for sure--if they had called him in, there must have been plenty interference--and the kind that didn't stop at murder. Frontier towns and frontier wilderness didn't pay much attention to city-made laws. Tesno carried his own law with him and he knew he'd have to make it respected. It was the law of the six-gun and the firm high hand. Take no guff, keep your powder dry, and don't give an inch. One moment of uncertainty, and it would mean his end! - Summary by William O. Turner

The History of Philosophy is the exposition of philosophical opinions and of systems and schools of philosophy. It includes the study of the lives of philosophers, the inquiry into the mutual connection of schools and systems of thought, and the attempt to trace the course of philosophical progress. Topics covered include Ancient Philosophy (Babylon, China, India, Egypt, Greece and Rome) Christian Era Philosophy (St. Anselm, Thomas Aquinas, William of Ockam) and Modern Philosophy (including Descartes, Spinoza, Kant and Hegel.) (Summary by Beth Thomas and the Introduction)

Through personal experience and extensive travel in Mexico in the late 1900s, the author of “Barbarous Mexico” depicts the circumstances that will trigger the Mexican Revolution of 1910. The rampant, government sanctioned, widespread abuse of human rights in the tobacco and corn plantations of Central and Southeastern Mexico created an atmosphere where peasants, and the working class at large, had to choose between their lives and the revolution. Turner presents a gruesome picture of political and ethnic slavery; how President Diaz policies promoted, encouraged and maintained the system; how foreign actors sanctioned the practices; and ends with an encouraging vision of the Mexican people as a whole. (Summary by Mario Pineda)