41 research outputs found
Oligodendroglial Process Formation is Differentially Affected by Modulating the Intra- and Extracellular Cholesterol Content
Cholesterol is an essential component of eukaryotic plasma membranes and plays an important role in membrane organization and signaling processes. It is the major lipid component of detergent resistant caveolin-1 containing rafts which previously had been reported as a platform for nerve growth factor (NGF) signaling in oligodendrocytes (OL). Surprisingly, a knockdown of caveolin-1 attenuated the process formation of OL (Schmitz et al. J Neurosci Res 88:572–588, 2010), for which a loss of cholesterol could be responsible. In the present report, we could show that a caveolin-1 knockdown resulted in an elevation of cellular cholesterol level; it may indicate an important role of caveolin-1 in cholesterol trafficking to the plasma membrane. Treatment with exogenous PEG cholesterol, which was incorporated to the plasma membrane, supported oligodendroglial process formation, in particular when OL were stimulated by NGF. In this context we have found that OL express NPC1L1 (Niemann–Pick disease type C1-Like 1) which could modulate cholesterol uptake. In contrast, depletion of membrane-bound cholesterol diminished NGF-induced process formation concomitant with a reduced activity of p42/44 mitogen-activated protein kinases
Effect of Cavtratin, a Caveolin-1 Scaffolding Domain Peptide, on Oligodendroglial Signaling Cascades
Caveolin and caveolin containing rafts are involved in the signaling of growth factors in various cell types. Previous reports of our lab indicated a co-localization of caveolin and the high affinity nerve growth factor (NGF) receptor tyrosine kinase A (TrkA). Mutual effects have been observed among which a caveolin-1 knock-down resulted in an impairment of the NGF signaling cascade rather than in an increase of activity as expected from other growth factor reports. On the other hand, an over-expression of caveolin-1 impaired the NGF stimulated activity of p42/44 mitogen activated protein kinases (MAPK). In this study, we used a caveolin-1 scaffolding domain (CSD) peptide (cavtratin) of which an inhibitory effect on growth factor receptors was reported. Our data showed that cavtratin suppresses the NGF-induced phosphorylation of TrkA as well as the activation of MAPK in porcine oligodendrocytes significantly
Social interaction style of children and adolescents with high-functioning autism spectrum disorder
Qualitative differences in social interaction style exist within the autism spectrum. In this study we examined whether these differences are associated with (1) the severity of autistic symptoms and comorbid disruptive behavior problems, (2) the child's psycho-social health, and (3) executive functioning and perspective taking skills. The social interaction style of 156 children and adolescents (6-19 years) with high-functioning autism spectrum disorder (HFASD) was determined with the Wing Subgroups Questionnaire. An active-but-odd social interaction style was positively associated with symptoms of autism, attention deficit and hyperactivity. Furthermore, an active-but-odd social interaction style was negatively associated with children's psycho-social health and positively with executive functioning problems. Social interaction style explains part of the heterogeneity among children with HFASD
Management of Cerebral Venous Thrombosis Due to Adenoviral COVID-19 Vaccination
Objective Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality. Methods We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis. Results Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p < 0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR = 0.19, 95% CI = 0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR = 0.70, 95% CI = 0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR = 2.19, 95% CI = 0.74-6.54). Conclusions In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022Peer reviewe
Bottom trawl fishing footprints on the world’s continental shelves
Publication history: Accepted - 23 August 2018; Published online - 8 October 2018.Bottom trawlers land around 19 million tons of fish and invertebrates
annually, almost one-quarter of wild marine landings. The extent of
bottom trawling footprint (seabed area trawled at least once in a
specified region and time period) is often contested but poorly
described. We quantify footprints using high-resolution satellite vessel
monitoring system (VMS) and logbook data on 24 continental shelves
and slopes to 1,000-m depth over at least 2 years. Trawling footprint
varied markedly among regions: from <10% of seabed area in Australian
and New Zealand waters, the Aleutian Islands, East Bering Sea,
South Chile, and Gulf of Alaska to >50% in some European seas.
Overall, 14% of the 7.8 million-km2 study area was trawled, and
86% was not trawled. Trawling activity was aggregated; the most
intensively trawled areas accounting for 90% of activity comprised
77% of footprint on average. Regional swept area ratio (SAR; ratio
of total swept area trawled annually to total area of region, a metric
of trawling intensity) and footprint area were related, providing an
approach to estimate regional trawling footprints when highresolution
spatial data are unavailable. If SAR was ≤0.1, as in 8 of
24 regions, therewas >95% probability that >90%of seabed was not
trawled. If SAR was 7.9, equal to the highest SAR recorded, there
was >95% probability that >70% of seabed was trawled. Footprints
were smaller and SAR was ≤0.25 in regions where fishing rates consistently
met international sustainability benchmarks for fish stocks,
implying collateral environmental benefits from sustainable fishing.Funding for meetings of the study group and salary
support for R.O.A. were provided by the following: David and Lucile Packard
Foundation; the Walton Family Foundation; the Alaska Seafood Cooperative;
American Seafoods Group US; Blumar Seafoods Denmark; Clearwater Seafoods
Inc.; Espersen Group; Glacier Fish Company LLC US; Gortons Seafood; Independent
Fisheries Limited N.Z.; Nippon Suisan (USA), Inc.; Pesca Chile S.A.;
Pacific Andes International Holdings, Ltd.; San Arawa, S.A.; Sanford Ltd. N.Z.;
Sealord Group Ltd. N.Z.; South African Trawling Association; Trident Seafoods;
and the Food and Agriculture Organisation of the United Nations. Additional
funding to individual authors was provided by European Union Project
BENTHIS EU-FP7 312088 (to A.D.R., O.R.E., F.B., N.T.H., L.B.-M., R.C., H.O.F.,
H.G., J.G.H., P.J., S.K., M.L., G.G.-M., N.P., P.E.P., T.R., A.S., B.V., and M.J.K.); the
Instituto Português do Mar e da Atmosfera, Portugal (C.S.); the International
Council for the Exploration of the Sea Science Fund (R.O.A. and K.M.H.); the
Commonwealth Scientific and Industrial Research Organisation (C.R.P. and
T.M.); the National Oceanic and Atmospheric Administration (R.A.M.); New
Zealand Ministry for Primary Industries Projects BEN2012/01 and DAE2010/
04D (to S.J.B. and R.F.); the Institute for Marine and Antarctic Studies, University
of Tasmania and the Department of Primary Industries, Parks, Water and
Environment, Tasmania, Australia (J.M.S.); and UK Department of Environment,
Food and Rural Affairs Project MF1225 (to S.J.)