Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis

Ubiquitin-positive, tau- and alpha-synuclein-negative inclusions are hallmarks of frontotemporal lobar degeneration with ubiquitin-positive inclusions and amyotrophic lateral sclerosis. Although the identity of the ubiquitinated protein specific to either disorder was unknown, we showed that TDP-43 is the major disease protein in both disorders. Pathologic TDP-43 was hyper-phosphorylated, ubiquitinated, and cleaved to generate C-terminal fragments and was recovered only from affected central nervous system regions, including hippocampus, neocortex, and spinal cord. TDP-43 represents the common pathologic substrate linking these neurodegenerative disorders.     

Progress in the capture, manipulation, and delivery of medical media and its impact on education, clinical care, and research

In this article, advances in the application of medical media to education, clinical care, and research are explored and illustrated with examples, and their future potential is discussed. Impact is framed in terms of the Sloan Consortium's five pillars of quality education: access; student and faculty satisfaction; learning effectiveness; and cost effectiveness. (Hiltz SR, Zhang Y, Turoff M. Studies of effectiveness of learning networks. In Bourne J, Moore J, ed. Elements of Quality Online Education. Needham, MA: Sloan-Consortium, 2002:15-45). The alternatives for converting analog media (text, photos, graphics, sound, video, animations, radiographs) to digital media and direct digital capture are covered, as are options for storing, manipulating, retrieving, and sharing digital collections. Diagnostic imaging is given particular attention, clarifying the difference between computerized radiography and digital radiography and explaining the accepted standard (DICOM) and the advantages of Web PACS. Some novel research applications of medical media are presented.     

Spontaneous aortic dissecting hematoma in two dogs.

This report describes 2 cases of spontaneous aortic dissecting hematoma in young Border Collie and Border Collie crossbred dogs. Histology was performed in one of the cases involving an unusual splitting of the elastin present within the wall of the aorta, consistent with elastin dysplasia as described in Marfan syndrome in humans. The first case involved a young purebred Border Collie that died suddenly and the second case involved a Border Collie crossbred dog that died after a 1-month history of seizures. Gross lesions included pericardial tamponade with dissection of the ascending aorta in the former case and thoracic cavity hemorrhage, mediastinal hematoma, and aortic dissection in the latter. Histologic lesions in the case of the Border Collie crossbred dog included a dissecting hematoma of the ascending aorta with elastin dysplasia and right axillary arterial intimal proliferation.     

Observations on the reproductive cycles of Cellana capensis (Gmelin, 1791) and Patella concolor Krauss, 1848 (Gastropoda: Prosobranchia: Patellidae)

The reproductive periodicities of the patellid limpets Cellana capensis and Patella concolor were determined from changes in macro-and microscopic appearance of the gonads over a 14-month period. Both species appear to have protracted breeding periods with several peaks in spawning activity. Problems encountered with the application of standard sampling and analytical methods to species with such cycles are discussed.     

Use of observed wild bird activity on poultry farms and a literature review to target species as high priority for avian influenza testing in 2 regions of Canada

The risk of avian influenza outbreaks in poultry is partially dependent on the probability of contact between domestic poultry and wild birds shedding avian influenza (AI) virus. The major objective of this study was to document wild bird activity on poultry farms to determine which wild bird species should be targeted for AI surveillance in Canada. We collected data in 2 major poultry producing regions of Canada, southwestern Ontario and the Fraser Valley of British Columbia, on the relative abundance of various wild bird species found on poultry farms and on how these species utilized habitat around poultry farms. We reviewed the published literature to determine what was known about AI pathobiology in the species we observed. From these results we created a list of 10 wild bird species that are a priority for further study. These species are the European starling, barn swallow, rock dove, American crow, northwestern crow, American robin, dark-eyed junco, song sparrow, horned lark, and common grackle. Abundance of these and other species varied between provinces and seasons.     

HSPC117 is the essential subunit of a human tRNA splicing ligase complex

Splicing of mammalian precursor transfer RNA (tRNA) molecules involves two enzymatic steps. First, intron removal by the tRNA splicing endonuclease generates separate 5' and 3' exons. In animals, the second step predominantly entails direct exon ligation by an elusive RNA ligase. Using activity-guided purification of tRNA ligase from HeLa cell extracts, we identified HSPC117, a member of the UPF0027 (RtcB) family, as the essential subunit of a tRNA ligase complex. RNA interference-mediated depletion of HSPC117 inhibited maturation of intron-containing pre-tRNA both in vitro and in living cells. The high sequence conservation of HSPC117/RtcB proteins is suggestive of RNA ligase roles of this protein family in various organisms.     

Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis

Soluble oligomers are common to most amyloids and may represent the primary toxic species of amyloids, like the Abeta peptide in Alzheimer's disease (AD). Here we show that all of the soluble oligomers tested display a common conformation-dependent structure that is unique to soluble oligomers regardless of sequence. The in vitro toxicity of soluble oligomers is inhibited by oligomer-specific antibody. Soluble oligomers have a unique distribution in human AD brain that is distinct from fibrillar amyloid. These results indicate that different types of soluble amyloid oligomers have a common structure and suggest they share a common mechanism of toxicity.     

Place,Taste, or Face-to-Face? Understanding Producer–Consumer Networks in “Local” Food Systems in Washington State

In an increasingly globalized food economy, local agri-food initiatives are promoted as more sustainable alternatives, both for small-scale producers and ecologically conscious consumers. However, revitalizing local agri-food communities in rural agro-industrial regions is particularly challenging. This case study examines Grant and Chelan Counties, two industrial farming regions in rural Central Washington State, distant from the urban fringe. Farmers in these counties have tried diversifying large-scale processing into organics and marketing niche and organic produce at popular farmers markets in Seattle about 200 miles away. Such strategies invoke the question, “How are ‘local’ agri-food networks socially and geographically defined?” The meaning of what constitutes “local” and/or “sustainable” systems merits consideration in the linking of these rural counties with distant urban farmers markets. Employing historical, in-depth interview and survey research, we analyze production and consumption networks and the non-market systems that residents in these counties access for self-provisioning and food security.