Autophagy dysregulation in cell culture and animals models of Spinal Muscular Atrophy

Abnormal autophagy has become a central thread linking neurodegenerative diseases, particularly of the motor neuron. One such disease is spinal muscular atrophy (SMA), a genetic neuromuscular disorder caused by mutations in the SMN1 gene resulting in low levels of Survival Motor Neuron (SMN) protein. Despite knowing the causal protein, the exact intracellular processes that are involved in the selective loss of motor neurons remains unclear. Autophagy induction can be helpful or harmful depending on the situation, and we sought to understand the state of the autophagic response in SMA. We show that cell culture and animal models demonstrate induction of autophagy accompanied by attenuated autophagic flux, resulting in the accumulation of autophagosomes and their associated cargo. Expression of the SMN-binding protein a-COP, a known modulator of autophagic flux, can ameliorate this autophagic traffic jam

Contaminant Levels in Eggs of American White Pelicans, Pelecanus erythrorhynchos, from Chase Lake, North Dakota

American White Pelicans (Pelecanus erythrorhynchos) are colonial nesters, making them susceptible to site-specific mortality factors. One of the largest known breeding colonies is at Chase Lake National Wildlife Refuge in North Dakota. In 2004, this colony suffered total reproductive failure. In 2005, we collected abandoned eggs from this colony to test for environmental contaminants. Nine eggs were analyzed for 28 organochlorine pesticides, total polychlorinated biphenyls, and 26 inorganic elements. Based on concentrations in this sample of eggs and levels linked to reproductive problems in birds, adult pelicans in the Chase Lake breeding colony are not at known risk from any of the environmental contaminants we measured

Report of Data Analyses to the Georgia Commission on the Efficacy of the CON Program

A highlight of presentations and discussions during the Philanthropic Symposium on School Health held October 16, 2000 in Atlanta, GA.Community and Public Healt

The Legacy Project: Rodney L. Custer, DTE

An interview with vice president of Dept. of Technical Education, Rodney Custer is presented. Topics discussed include interest in technology and engineering education; academic qualification; and experience as university department chair administrator and working with the Center for Math, Science, and Technology (CeMast)

Periorbital edema secondary to imatinib mesylate

Collin M McClelland, George J Harocopos, Philip L CusterSchool of Medicine, Washington University, St. Louis, MO, USAAbstract: Imatinib mesylate (Gleevec®) is a well-established pharmacologic treatment for all phases of chronic myeloid leukemia and for advanced gastrointestinal stromal tumors (GISTs). Edema-related side effects are relatively common in imatinib therapy with the periocular skin representing one of the most common sites for localized edema. While the adverse effect of periorbital edema with imatinib is well documented in the oncology literature, there is limited reference to this common reaction in the ophthalmology literature. We report two patients with upper eyelid edema associated with imatinib therapy who required surgical intervention to ameliorate significant visual field obstruction. We highlight the details of each case including the histopathologic findings of excised redundant skin followed by a thorough review of the literature on imatinib related periorbital edema.Keywords: imatinib mesylate, gleevec, edema, periorbital edema, tyrosine kinase inhibito

Illustrated Workbook for the Detection of Plant Viruses Infecting Cucurbits: Demonstration of the Use of Direct Immunoblotting Assays

There are at least 5 viruses of cucurbitaceous plants (squash, melons, cucumber, etc.) that frequently cause severe to complete economic loss for cucurbit producers in the tropics. These viruses are: zucchini yellow mosaic virus (ZYMV), papaya ringspot virus watermelon isolate (PRSV-W, formerly watermelon mosaic virus 1 or WMV I), watermelon mosaic virus 2 (WMV 2), cucumber mosaic virus (CMV) and squash mosaic virus (SqMV). To accurately diagnose virus infections you must use a detection technique. Many techniques are available, including host plant range analysis and serological and molecular analysis. The purpose of our workshop and this illustrated workbook is to demonstrate the use of a serological technique called direct immunoblotting. The advantage of this technique is that it requires very little special equipment, the assay is relatively easy to perform and the assay has some characteristics that make it ideal for diagnosing problems associated with surveying island communities.Funded through the U.S. Department of Agriculture Cooperative State Research, Education, and Extension Service Grant 99-38826-785

Atmospheric methanol measurement using selective catalytic methanol to formaldehyde conversion

International audienceA novel atmospheric methanol measurement technique, employing selective gas-phase catalytic conversion of methanol to formaldehyde followed by detection of the formaldehyde product, has been developed and tested. The effects of temperature, gas flow rate, gas composition, reactor-bed length, and reactor-bed composition on the methanol conversion efficiency of a molybdenum-rich, iron-molybdate catalyst [Mo-Fe-O] were studied. Best results were achieved using a 1:4 mixture (w/w) of the catalyst in quartz sand. Optimal methanol to formaldehyde conversion (>95% efficiency) occurred at a catalyst housing temperature of 345°C and an estimated sample-air/catalyst contact time of <0.2 seconds. Potential interferences arising from conversion of methane and a number of common volatile organic compounds (VOC) to formaldehyde were found to be negligible under most atmospheric conditions and catalyst housing temperatures. Using the new technique, atmospheric measurements of methanol were made at the University of Bremen campus from 1 to 15 July 2004. Methanol mixing ratios ranged from 1 to 5 ppb with distinct maxima at night. Formaldehyde mixing ratios, obtained in conjunction with methanol by periodically bypassing the catalytic converter, ranged from 0.2 to 1.6 ppb with maxima during midday. These results suggest that selective, catalytic methanol to formaldehyde conversion, coupled with existing formaldehyde measurement instrumentation, is an inexpensive and effective means for monitoring atmospheric methanol

Abnormal Golgi morphology and decreased COPI function in cells with low levels of SMN

We report here the finding of abnormal Golgi apparatus morphology in motor neuron like cells depleted of SMN as well as Golgi apparatus morphology in SMA patient fibroblasts. Rescue experiments demonstrate that this abnormality is dependent on SMN, but can also be rescued by expression of the COPI coatomer subunit alpha-COP. A motor neuron-like cell line containing an inducible alpha-COP shRNA was created to generate a parallel system to study knockdown of SMN or alpha-COP. Multiple assays of COPI-dependent intracellular trafficking in cells depleted of SMN demonstrate that alpha-COP function is suboptimal, including failed sequestration of plasma membrane proteins, altered binding of mRNA, and defective targeting and transport of Golgi-resident proteins

Transgenic mice expressing mutant forms VCP/p97 recapitulate the full spectrum of IBMPFD including degeneration in muscle, brain and bone

Inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD) is a dominantly inherited degenerative disorder caused by mutations in the valosin-containing protein (VCP) gene. VCP (p97 in mouse, TER94 in Drosophila melanogaster and CDC48 in Saccharomyces cerevisiae) is a highly conserved AAA+-ATPase that regulates a wide array of cellular processes. The mechanism of IBMPFD pathogenesis is unknown. Towards elucidating the pathogenic mechanism we have developed and characterized transgenic mice with ubiquitous expression of wild-type and disease-causing versions of human VCP/p97. Here, we report that mice expressing VCP/p97 harboring the mutations R155H or A232E develop pathology that is limited to muscle, brain and bone, recapitulating the spectrum of disease in humans with IBMPFD. The mice exhibit progressive muscle weakness and pathological examination of muscle shows classic characteristics of inclusion body myopathy including rimmed vacuoles and TDP-43 pathology. The mice exhibit abnormalities in behavioral testing and pathological examination of the brain shows widespread TDP-43 pathology. Furthermore, radiological examination of the skeleton reveals that mutant mice develop severe osteopenia accompanied by focal lytic and sclerotic lesions in vertebrae and femur. In vitro studies indicate that mutant VCP causes inappropriate activation of the NF-κB signaling cascade, which could contribute to the mechanism of pathogenesis in multiple tissues including muscle, bone and brai