Rapid axonal transport in focally demyelinated sciatic nerve

Focal demyelination was produced in rat sciatic nerve by unilateral intraneural injection of anti-galactocerebroside serum. A functional lesion was confirmed by the presence of nerve conduction block. Histologically, this corresponded to demyelination of 50-70% of the fibers in nerve cross sections; axonal structures appeared intact. At the time of maximal demyelination (7 d), 35S-methionine or 3H-fucose was injected bilaterally into the spinal cord ventral horn. At later times (5 hr-7 d), the sciatic nerve was removed and radioactivity in successive nerve segments was quantitated. The transport rates (approximately 260 mm/d) and the composition of transported proteins and glycoproteins (separated on 7-15% polyacrylamide gradient gels) were not altered in lesioned nerves relative to contralateral control nerves. Light microscopic autoradiographic analysis revealed a similar localization of axonally transported and deposited glycoproteins in demyelinated and control fibers. Initially (8 hr), the majority of label was over axons. Labeled glycoproteins remaining in the nerve after 1 week were retained mainly in axolemmal regions. We conclude that acute focal primary demyelination does not lead to major alterations in the transport or deposition of newly synthesized macromolecules

Host spatiotemporal overlap in a park with high endemicity of Echinococcus multilocularis

There has been a spate of recent cases of human alveolar echinococcosis (AE) in Alberta, Canada. Alveolar echinococcosis is caused by Echinococcus multilocularis, which is prevalent among coyote populations and present in domestic dogs in Alberta. Using qPCR, we estimated the seasonal fecal prevalence of E. multilocularis in coyotes and dogs in a multiuse recreation area close to Edmonton, Alberta, where we also setup remote cameras to model seasonal changes in the overlap in temporal activity and the spatial intensity of use among coyotes, humans, and dogs, as a proxy of potential transmission. We detected E. multilocularis in 18 of 137 wild canid feces and none in 44 dog feces. After correcting for the qPCR test’s sensitivity and specificity, we estimated at 15.7% (9.7-22.7%, 95% CrI) the true fecal prevalence for coyotes. Temporal overlap between coyotes and both humans and dogs increased in the fall and winter relative to the spring and summer. Coyote intensity of use showed seasonal variations and was higher on maintained trails and locations closer to visitor parking and at sites with high intensity of dog use. Our results reinforce the need of an integrated approach, typical of both One-Health and Eco-Health, to park management for minimizing the likelihood of transmission where human and dog activity results in significant overlap with the one of the natural definitive hosts of zoonotic parasites

Diurnal and dietary-induced changes in cholesterol synthesis correlate with levels of mRNA for HMG-CoA reductase

We determined the extent to which diurnal variation in cholesterol synthesis in liver is controlled by steady-state mRNA levels for the rate-limiting enzyme in the pathway, hydroxymethylglutaryl (HMG)-CoA reductase. Rats 30 days of age and maintained on a low-cholesterol diet since weaning were injected intraperitoneally wit

Deposition and transfer of axonally transported phospholipids in rat sciatic nerve

Radioactive glycerol, ethanolamine, or choline injected into the vicinity of the cell bodies of rat sciatic nerve sensory fibers is incorporated into phospholipid. Some newly synthesized ethanolamine and choline phosphoglycerides are subsequently committed to transport down the sciatic nerve axons at a rate of several hundred millimeters per day. Most labeled choline phosphoglycerides move uniformly down the axons; in contrast, the crest of moving ethanolamine phosphoglycerides is continually attenuated. These data, as well as differences in the clearance of these phospholipids distal to a nerve ligature, suggest that various classes of labeled phospholipids are differentially unloaded from the transport vector (possibly by exchange with unlabeled lipid in stationary axonal structures) during movement down the axons. The extent of unloading appears to be defined by the base moiety; both diacyl and plasmalogen species of ethanolamine phosphoglycerides exchange extensively with stationary axonal lipids, while most choline phosphoglycerides continue down the axons. Autoradiographic studies with 3H-choline and 3H-ethanolamine demonstrated that most unloaded phospholipid is initially deposited in axonal structures; some of this unloaded lipid is subsequently transferred to the axon/myelin interface (axolemma?) and then to myelin. Although transported ethanolamine phosphoglycerides exchange more extensively with lipids in stationary axonal structures than do choline phosphoglycerides, at early times more label from 3H-choline is found in myelin. A model to resolve this seeming discrepancy is proposed, wherein a differential topographic localization of phospholipid classes in the membrane of the transport vector allows for a preferential extensive exchange of transported ethanolamine phosphoglycerides with lipids in stationary axonal structures, while choline phosphoglycerides become available for rapid transfer to myelin by a process involving vesicle fusion with axolemma

Prognostic implications of physiologic and radiographic changes in idiopathic interstitial pneumonia

Idiopathic interstitial pneumonias are a diverse group of lung diseases with varied prognoses. We hypothesized that changes in physiologic and radiographic parameters would predict survival. We retrospectively examined 80 patients with usual interstitial pneumonia and 29 patients with nonspecific interstitial pneumonia. Baseline characteristics were examined together with 6-month change in forced vital capacity, diffusing capacity for carbon monoxide, and ground glass infiltrate and fibrosis on high resolution computed tomography. Patients with usual interstitial pneumonia were more likely to have a statistically significant or marginally significant decline in lung volume, diffusing capacity for carbon monoxide, and an increase in ground glass infiltrates (p <= 0.08) compared with patients with nonspecific interstitial pneumonia. For patients with usual interstitial pneumonia, change in forced vital capacity was the best physiologic predictor of mortality (p = 0.05). In a multivariate Cox proportional hazards model controlling for histopathologic diagnosis, gender, smoking history, baseline forced vital capacity, and 6-month change in forced vital capacity, a decrease in forced vital capacity remained an independent risk factor for mortality (decrease > 10%; hazard ratio 2.47; 95% confidence interval 1.29, 4.73; p = 0.006). We conclude that a 6-month change in forced vital capacity gives additional prognostic information to baseline features for patients with idiopathic interstitial pneumonia.Supported by National Institutes of Health NHLBI grants P50HL46487, NIH/NCRR 3 MO1 RR00042-33S3, NIH/NIA P60 AG08808-06, NHLBI, 1 K24 HL04212, and 1 K23 HL68713.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91973/1/2003 AJRCCM - Prognostic Implications of Physiologic and Radiographic Changes in Idiopathic Interstitial Pneumonia.pd

Prognostic value of desaturation during a six minute walk test in Idiopathic Interstitial Pneumonia

Exercise-induced hypoxia is an index of the severity of interstitial lung disease. We hypothesized that desaturation during a 6-minute walk test would predict mortality for patients with usual interstitial pneumonia (n = 83) and nonspecific interstitial pneumonia (n = 22). Consecutive patients with biopsy-proven disease performed a 6-minute walk test between January 1996 and December 2001. Desaturation was defined as a fall in oxygen saturation to 88% or less during the 6-minute walk test. Desaturation was common (44 of 83 usual interstitial pneumonia and 8 of 22 nonspecific interstitial pneumonia; chi square, p = 0.39). Patients with usual interstitial pneumonia or nonspecific interstitial pneumonia who desaturated had a significantly higher mortality than patients who did not desaturate (respective log-rank tests, p = 0.0018, p = 0.0089). In patients with usual interstitial pneumonia, the presence of desaturation was associated with an increased hazard of death (hazard ratio, 4.2; 95% confidence interval, 1.40, 12.56; p = 0.01) after adjusting for age, sex, smoking, baseline diffusion capacity for carbon monoxide, FVC, and resting saturation.Weconclude that knowledge of desaturation during a 6-minute walk test adds prognostic information for patients with usual interstitial pneumonia and nonspecific interstitial pneumonia.Supported in part by National Institutes of Health NHLBI Grant #P50HL46487, NHLBI, 1 K24 HL04212, and 1 K23 HL68713.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91972/1/2003 AJRCCM - Prognostic value of desaturation during a six minute walk test in Idiopathic Interstitial Pneumonia.pd

Fibroblastic Foci in Usual Interstitial Pneumonia: Idiopathic versus Collagen Vascular Disease

A histologic feature of usual interstitial pneumonia is the presence of fibroblastic foci. As some patients with usual interstitial pneumonia and an underlying collagen vascular disease have a better prognosis, we hypothesized that they would have fewer fibroblastic foci. Pathologists reviewed surgical lung biopsies from 108 patients with usual interstitial pneumonia (nine with collagen vascular disease) and assigned a score (absent 0, mild 1, moderate 2, and marked 3) for fibroblastic foci. Patients with idiopathic usual interstitial pneumonia had a higher median profusion of fibroblastic foci (1.75 vs. 1.0, p = 0.003). Baseline characteristics were similar, although patients with a collagen vascular disease were younger, had a shorter duration of symptoms, and had a higher percentage of predicted total lung capacity. Profusion of fibroblastic foci was the most discriminative feature for separating idiopathic from collagen vascular disease–associated usual interstitial pneumonia (odds ratio 8.31; 95% confidence interval, 1.98, 59.42; p = 0.002 for a one-unit increase in fibroblastic foci score). No deaths were noted in the collagen vascular disease–associated usual interstitial pneumonia group; 52 deaths occurred in the idiopathic usual interstitial pneumonia group (log rank; p = 0.005). We conclude that patients with collagen vascular disease–associated usual interstitial pneumonia have fewer fibroblastic foci and improved survival.Supported in part by National Institutes of Health National Heart, Lung, and Blood Institute grant #P50HL46487, NIH/NCRR 3 MO1 RR00042–33S3, NIH/NIA P60 AG08808–06, NHLBI 1 K24 HL04212, and 1 K23 HL68713.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91974/1/2003 AJRCCM - Fibroblastic Foci in Usual Interstitial Pneumonia -Idiopathic versus Collagen Vascular Disease.pd

Primary demyelination induced by exposure to tellurium alters Schwann cell gene expression: a model for intracellular targeting of NGF receptor

Exposure of developing rats to tellurium results in a highly synchronous segmental demyelination of peripheral nerves with sparing of axons; this demyelination is followed closely by a period of rapid remyelination. Demyelination occurs subsequent to a tellurium-induced block in the synthesis of cholesterol, the major myelin lipid. We utilized the techniques of Northern blotting, in situ hybridization, and immunocytochemistry to examine temporal alterations in Schwann cell gene expression related to demyelination and remyelination. Tellurium- induced demyelination is associated with downregulation of myelin protein expression and a corresponding upregulation of NGF receptor (NGF-R) and glial fibrillary acidic protein (GFAP) expression. Steady- state mRNA levels (expressed on a “per nerve” basis) for P0, the major myelin protein, were decreased by about 50% after 5 d of tellurium exposure, while levels of mRNA for NGF-R and GFAP were markedly increased (about 15-fold). In situ hybridization of teased fibers suggested that the increase in steady-state mRNA levels for NGF-R was primarily associated with demyelinated internodes and not with adjacent unaffected internodes. Although P0 message was almost totally absent from demyelinating internodes, it was also reduced in normal-appearing internodes as well. This suggests that limiting the supply of a required membrane component (cholesterol) may lead to partial downregulation of myelin gene expression in all myelinating Schwann cells. In partially demyelinated internodes, NGF-R and GFAP immunofluorescence appeared largely confined to the demyelinated regions. This suggests specific targeting of these proteins to local areas of the Schwann cell where there is myelin loss. These results demonstrate that demyelination is associated with reversion of the affected Schwann cells to a precursor cell phenotype. Because axons remain intact, our results suggest that these changes in Schwann cell gene expression do not require input from a degenerating axon, but instead may depend on whether concerted synthesis of myelin is occurring

Educational archaeology and the practice of utopian pedagogy

This paper explores the idea, and some elements of the (potential) practice, of utopian pedagogy. It begins by outlining the general aims of ‘utopian pedagogy’ and notes the shift within contemporary writings away from the metaphor of the architect (armed with a utopian ‘blueprint’) towards that of the archaeologist. The ontological underpinnings of educational archaeology are discussed before attention turns to a critical examination of the pedagogical process of excavation. The key questions here are (to labour the metaphor) where to dig and how to identify a utopian find. The paper argues that, without a substantive normative vision to serve as a guide, utopian archaeology is conceptually flawed and practically ineffectual, romanticising an endlessly open process of exploration. The final section suggests that the fears associated with utopian architecture (authoritarian imposition, totalising closure) are misplaced and that drawing up a ‘blueprint’ should be the aim and responsibility of utopian pedagogy

Levers and leverage points for pathways to sustainability

Humanity is on a deeply unsustainable trajectory. We are exceeding planetary boundaries and unlikely to meet many international sustainable development goals and global environmental targets. Until recently, there was no broadly accepted framework of interventions that could ignite the transformations needed to achieve these desired targets and goals. As a component of the IPBES Global Assessment, we conducted an iterative expert deliberation process with an extensive review of scenarios and pathways to sustainability, including the broader literature on indirect drivers, social change and sustainability transformation. We asked, what are the most important elements of pathways to sustainability? Applying a social–ecological systems lens, we identified eight priority points for intervention (leverage points) and five overarching strategic actions and priority interventions (levers), which appear to be key to societal transformation. The eight leverage points are: (1) Visions of a good life, (2) Total consumption and waste, (3) Latent values of responsibility, (4) Inequalities, (5) Justice and inclusion in conservation, (6) Externalities from trade and other telecouplings, (7) Responsible technology, innovation and investment, and (8) Education and knowledge generation and sharing. The five intertwined levers can be applied across the eight leverage points and more broadly. These include: (A) Incentives and capacity building, (B) Coordination across sectors and jurisdictions, (C) Pre-emptive action, (D) Adaptive decision-making and (E) Environmental law and implementation. The levers and leverage points are all non-substitutable, and each enables others, likely leading to synergistic benefits. Transformative change towards sustainable pathways requires more than a simple scaling-up of sustainability initiatives—it entails addressing these levers and leverage points to change the fabric of legal, political, economic and other social systems. These levers and leverage points build upon those approved within the Global Assessment's Summary for Policymakers, with the aim of enabling leaders in government, business, civil society and academia to spark transformative changes towards a more just and sustainable world. A free Plain Language Summary can be found within the Supporting Information of this article.Fil: Chan, Kai M. A.. University of British Columbia; CanadáFil: Boyd, David R.. University of British Columbia; CanadáFil: Gould, Rachelle. University of Vermont; Estados UnidosFil: Jetzkowitz, Jens. Staatliches Museum fur Naturkunde Stuttgart; AlemaniaFil: Liu, Jianguo. Michigan State University; Estados UnidosFil: Muraca, Bárbara. University of Oregon; Estados UnidosFil: Naidoo, Robin. University of British Columbia; CanadáFil: Beck, Paige. University of British Columbia; CanadáFil: Satterfield, Terre. University of British Columbia; CanadáFil: Selomane, Odirilwe. Stellenbosch University; SudáfricaFil: Singh, Gerald G.. University of British Columbia; CanadáFil: Sumaila, Rashid. University of British Columbia; CanadáFil: Ngo, Hien T.. Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services; AlemaniaFil: Boedhihartono, Agni Klintuni. University of British Columbia; CanadáFil: Agard, John. The University Of The West Indies; Trinidad y TobagoFil: de Aguiar, Ana Paula D.. Stockholms Universitet; SueciaFil: Armenteras, Dolors. Universidad Nacional de Colombia; ColombiaFil: Balint, Lenke. BirdLife International; Reino UnidoFil: Barrington-Leigh, Christopher. Mcgill University; CanadáFil: Cheung, William W. L.. University of British Columbia; CanadáFil: Díaz, Sandra Myrna. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Driscoll, John. University of British Columbia; CanadáFil: Esler, Karen. Stellenbosch University; SudáfricaFil: Eyster, Harold. University of British Columbia; CanadáFil: Gregr, Edward J.. University of British Columbia; CanadáFil: Hashimoto, Shizuka. The University Of Tokyo; JapónFil: Hernández Pedraza, Gladys Cecilia. The World Economy Research Center; CubaFil: Hickler, Thomas. Goethe Universitat Frankfurt; AlemaniaFil: Kok, Marcel. PBL Netherlands Environmental Assessment Agency; Países BajosFil: Lazarova, Tanya. PBL Netherlands Environmental Assessment Agency; Países BajosFil: Mohamed, Assem A. A.. Central Laboratory for Agricultural Climate; EgiptoFil: Murray-Hudson, Mike. University Of Botswana; BotsuanaFil: O'Farrell, Patrick. University of Cape Town; SudáfricaFil: Palomo, Ignacio. Basque Centre for Climate Change; EspañaFil: Saysel, Ali Kerem. Boğaziçi University; TurquíaFil: Seppelt, Ralf. Martin-universität Halle-wittenberg; AlemaniaFil: Settele, Josef. German Centre for Integrative Biodiversity Research-iDiv; AlemaniaFil: Strassburg, Bernardo. International Institute for Sustainability, Estrada Dona Castorina; BrasilFil: Xue, Dayuan. Minzu University Of China; ChinaFil: Brondízio, Eduardo S.. Indiana University; Estados Unido