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121.
Grumati P Coletto L Sabatelli P Cescon M Angelin A Bertaggia E Blaauw B Urciuolo A Tiepolo T Merlini L Maraldi NM Bernardi P Sandri M Bonaldo P 《Nature medicine》2010,16(11):1313-1320
Autophagy is crucial in the turnover of cell components, and clearance of damaged organelles by the autophagic-lysosomal pathway is essential for tissue homeostasis. Defects of this degradative system have a role in various diseases, but little is known about autophagy in muscular dystrophies. We have previously found that muscular dystrophies linked to collagen VI deficiency show dysfunctional mitochondria and spontaneous apoptosis, leading to myofiber degeneration. Here we demonstrate that this persistence of abnormal organelles and apoptosis are caused by defective autophagy. Skeletal muscles of collagen VI-knockout (Col6a1(-/-)) mice had impaired autophagic flux, which matched the lower induction of beclin-1 and BCL-2/adenovirus E1B-interacting protein-3 (Bnip3) and the lack of autophagosomes after starvation. Forced activation of autophagy by genetic, dietary and pharmacological approaches restored myofiber survival and ameliorated the dystrophic phenotype of Col6a1(-/-) mice. Furthermore, muscle biopsies from subjects with Bethlem myopathy or Ullrich congenital muscular dystrophy had reduced protein amounts of beclin-1 and Bnip3. These findings indicate that defective activation of the autophagic machinery is pathogenic in some congenital muscular dystrophies. 相似文献
122.
123.
Peter Veen Josef Fanta Ivan Raev Iovu-Adrian Biriş Jacques de Smidt Bert Maes 《Biodiversity and Conservation》2010,19(6):1805-1819
Despite extensive forest destruction in the Middle Ages and later intensive commercial forest management, remnants of virgin
forests remained spared in some Central, Eastern and South-Eastern European countries. These virgin forests are the last examples
of original forests in this part of Europe. That is why their protection becomes an important issue of current European forestry
and nature protection policy. But the knowledge about the location and the area of virgin forests in these countries is incomplete
up till now. This article has the prime goal to present a conceptual framework what virgin forests might be (“A conceptual framework for defining of virgin forests” section). Based on this framework, a working methodology has been tested in Bulgaria and Romania (“Results of the two national projects in Romania and in Bulgaria” section and further). For this reason two projects have been carried out by the Royal Dutch Society of Nature Conservation
(KNNV) in close co-operation with the Forestry Institutes in Romania and in Bulgaria. The results of these projects are described
in general terms and further analysis in the future is necessary to describe specific features like forest structure and spatial
heterogeneity of these forests. Based on the results of the inventory, principles of sustainable protection and management
of the mapped virgin forests were defined and described in the research reports. The usefulness of the inventory became evident
already during the EU pre-accession period of both countries while preparing the NATURA 2000 network. The remaining virgin
forests of temperate Europe are an inexhaustible source of ecological information about biodiversity, structure, natural processes
and overall functioning of undisturbed forest ecosystems. Their research will reveal information which can be used for ecological
restoration of man-made forests which are degraded through intensive forestry practices over the last centuries. The last
virgin forests of temperate Europe represent an irreplaceable part of the natural capital of Europe and are worth to be protected
by law. Their last remnants in South-Eastern and Eastern Europe are endangered by commercial activities. A full inventory
of remaining virgin forests in all countries of temperate Europe is a matter of highest urgency. A representative selection
of virgin forest sites should be declared by UNESCO as World Heritage Sites. 相似文献
124.
Craig Jamieson Robert A. Campbell Iain A. Cumming Kevin J. Gillen Jonathan Gillespie Bert Kazemier Michael Kiczun Yvonne Lamont Amanda J. Lyons John K.F. Maclean Frederic Martin Elizabeth M. Moir John A. Morrow John Pantling Zoran Rankovic Lynn Smith 《Bioorganic & medicinal chemistry letters》2010,20(20):6072-6075
Starting from lead compound 1, we demonstrate how X-ray structural data can be used to understand SAR and expediently optimize bioavailability in a novel series of AMPA receptor modulators, furnishing 5 with improved bioavailability and robust in vivo activity. 相似文献
125.
David M. Alba Salvador Moyà‐Solà Assumpció Malgosa Isaac Casanovas‐Vilar Josep M. Robles Sergio Almécija Jordi Galindo Cheyenn Rotgers Juan Vicente Bertó Mengual 《American journal of physical anthropology》2010,141(1):52-75
Pliopithecus (Pliopithecus) canmatensis sp. nov. is described from several Late Aragonian localities from Abocador de Can Mata (ACM) in els Hostalets de Pierola (Vallès‐Penedès Basin, Catalonia, Spain), spanning from ~11.7 to 11.6 Ma (C5r.3r subchron), and being correlated to the MN8 (reference locality La Grive L3). The ACM remains display a pliopithecine dental morphology with well‐developed pliopithecine triangles on M/2 and M/3. This, together with other occlusal details, negates an attribution to the subgenus Epipliopithecus. Although slightly smaller, the ACM remains are most similar in size to comparable elements of P. piveteaui and P. antiquus. Several occlusal details (such as the greater development of the buccal cingulid in lower molars) and dental proportions (M/3 much longer than M/2), however, indicate greater similarities with P. antiquus from Sansan and La Grive. The ACM remains, however, differ from P. antiquus in dental proportions as well as occlusal morphology of the lower molars (including the less peripheral position of the protoconid and more medial position of the hypoconulid, the more mesial position of the buccal cuspids as compared to the lingual ones, the narrower but distinct mesial fovea, the higher trigonid, and the more extensive buccal cingulid, among others). These differences justify a taxonomic distinction at the species level of the ACM pliopithecid remains with respect to P. antiquus. Previous pliopithecid findings from the Vallès‐Penedès Basin, previously attributed to P. antiquus, are neither attributable to the latter species nor to the newly erected one. Am J Phys Anthropol, 2010. © 2009 Wiley‐Liss, Inc. 相似文献
126.
Borgonie G Dierick M Houthoofd W Willems M Jacobs P Bert W 《The Biological bulletin》2010,219(3):268-276
Organisms living in extreme habitats require costly adaptations to cope with these conditions. Among the suggested potential benefits that trade off these costs is refuge from predation. To study these interactions in extreme environments, samples were taken in the cave Cueva de Villa Luz, Tabasco, Mexico, where more than 32 subterranean springs, some H(2)S rich, rise from the floor. Hydrogen sulfide gas plus oxygen is absorbed by freshwater, and oxidation forms concentrated sulfuric acid. Snottites, whitish hollow mucous tubes, hang from the ceiling of the cave. Fluid drops from these snottites were recorded as having pH values of 0-3. We report the discovery of a new species of nematode that thrives in the highly acidic environment of the snottite. Micro CT scan of snottites reveals a complex interaction between the acidic snottite, nematodes, and abundant nematode-eating mites. The nematode adaptation to low pH probably protects them against mite predation, for which nematodes are most likely the most important source of carbon in this sulfur-driven ecosystem. 相似文献
127.
Bert Hidding Bart A. Nolet Thijs de Boer Peter P. de Vries Marcel Klaassen 《Oecologia》2010,162(1):199-208
At least two distinct trade-offs are thought to facilitate higher diversity in productive plant communities under herbivory. Higher investment in defence and enhanced colonization potential may both correlate with decreased competitive ability in plants. Herbivory may thus promote coexistence of plant species exhibiting divergent life history strategies. How different seasonally tied herbivore assemblages simultaneously affect plant community composition and diversity is, however, largely unknown. Two contrasting types of herbivory can be distinguished in the aquatic vegetation of the shallow lake Lauwersmeer. In summer, predominantly above-ground tissues are eaten, whereas in winter, waterfowl forage on below-ground plant propagules. In a 4-year exclosure study we experimentally separated above-ground herbivory by waterfowl and large fish in summer from below-ground herbivory by Bewick’s swans in winter. We measured the individual and combined effects of both herbivory periods on the composition of the three-species aquatic plant community. Herbivory effect sizes varied considerably from year to year. In 2 years herbivore exclusion in summer reinforced dominance of Potamogeton pectinatus with a concomitant decrease in Potamogeton pusillus, whereas no strong, unequivocal effect was observed in the other 2 years. Winter exclusion, on the other hand, had a negative effect on Zannichellia palustris, but the effect size differed considerably between years. We suggest that the colonization ability of Z. palustris may have enabled this species to be more abundant after reduction of P. pectinatus tuber densities by swans. Evenness decreased due to herbivore exclusion in summer. We conclude that seasonally tied above- and below-ground herbivory may each stimulate different components of a macrophyte community as they each favoured a different subordinate plant species. 相似文献
128.
Mark van de Wouw Theo van Hintum Chris Kik Rob van Treuren Bert Visser 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2010,120(6):1241-1252
In recent years, an increasing number of papers has been published on the genetic diversity trends in crop cultivars released
in the last century using a variety of molecular techniques. No clear general trends in diversity have emerged from these
studies. Meta analytical techniques, using a study weight adapted for use with diversity indices, were applied to analyze
these studies. In the meta analysis, 44 published papers were used, addressing diversity trends in released crop varieties
in the twentieth century for eight different field crops, wheat being the most represented. The meta analysis demonstrated
that overall in the long run no substantial reduction in the regional diversity of crop varieties released by plant breeders
has taken place. A significant reduction of 6% in diversity in the 1960s as compared with the diversity in the 1950s was observed.
Indications are that after the 1960s and 1970s breeders have been able to again increase the diversity in released varieties.
Thus, a gradual narrowing of the genetic base of the varieties released by breeders could not be observed. Separate analyses
for wheat and the group of other field crops and separate analyses on the basis of regions all showed similar trends in diversity. 相似文献
129.
Bert Vander Cruyssen Patrick Durez Rene Westhovens Filip De Keyser 《Arthritis research & therapy》2010,12(3):1-8
Introduction
This study is based on the results from a Belgian expanded access program in which patients with active refractory and erosive rheumatoid arthritis (RA) were treated with intravenous infusions of infliximab in combination with methotrexate. The objectives of this study were to evaluate the continuation rate of infliximab and its clinical effect over a 7-year period and to document the reasons for discontinuation.Methods
Between 2000 and 2001, 511 patients with severe and refractory RA were enrolled and treated with infliximab. After 7 years, apart from routine clinical follow-up, treating rheumatologists were asked to complete a questionnaire designed specifically for the present study to evaluate the current therapy with infliximab, the level of disease activity (Disease Activity Score in 28 joints [DAS28]) and the reasons for infliximab discontinuation.Results
After 7 years, 160 of 511 patients (31%) were still on infliximab treatment. The major reasons for infliximab discontinuation included lack of efficacy (104 patients), adverse events (107 patients) and elective change of therapy (70 patients). The majority of cases of treatment discontinuation for safety reasons occurred during the first 2 years. In contrast, discontinuation due to ineffectiveness showed a more constant rate over the 7-year period. Mean DAS for patients still on treatment with infliximab decreased from 5.7 (standard error [SE] 0.1) at baseline to 3.0 (SE 0.1) at year 4 and remained that low until year 7 (3.0 [SE 0.1]). Low disease activity (defined as DAS28 <3.2) was present in 60.9% of patients, and 45.5% achieved remission (DAS28 <2.6). DAS28 at the time of treatment discontinuation due to ineffectiveness decreased over the 7-year period from 5.6 (SE 0.3) in 2001 to 4.8 (SE 0.3) in 2008.Conclusions
This observational study revealed that patients who continue to receive infliximab experience sustained clinical benefit. The majority of safety issues occurred during the first 2 years of infliximab therapy. We observed that the DAS at the time of therapy discontinuation showed a trend to decrease over time. 相似文献130.
Hafer N Maidment BW Hatchett RJ 《Biosecurity and bioterrorism : biodefense strategy, practice, and science》2010,8(4):357-363
The National Institute of Allergy and Infectious Diseases (NIAID) Radiation/Nuclear Medical Countermeasures Development Program has developed an integrated approach to providing the resources and expertise required for the research, discovery, and development of radiation/nuclear medical countermeasures (MCMs). These resources and services lower the opportunity costs and reduce the barriers to entry for companies interested in working in this area and accelerate translational progress by providing goal-oriented stewardship of promising projects. In many ways, the radiation countermeasures program functions as a "virtual pharmaceutical firm," coordinating the early and mid-stage development of a wide array of radiation/nuclear MCMs. This commentary describes the radiation countermeasures program and discusses a novel business model that has facilitated product development partnerships between the federal government and academic investigators and biopharmaceutical companies. 相似文献