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71.
Tatyana A. Shelkovnikova Owen M. Peters Alexey V. Deykin Natalie Connor-Robson Hannah Robinson Alexey A. Ustyugov Sergey O. Bachurin Tatyana G. Ermolkevich Igor L. Goldman Elena R. Sadchikova Elena A. Kovrazhkina Veronica I. Skvortsova Shuo-Chien Ling Sandrine Da Cruz Philippe A. Parone Vladimir L. Buchman Natalia N. Ninkina 《The Journal of biological chemistry》2013,288(35):25266-25274
Dysfunction of two structurally and functionally related proteins, FUS and TAR DNA-binding protein of 43 kDa (TDP-43), implicated in crucial steps of cellular RNA metabolism can cause amyotrophic lateral sclerosis (ALS) and certain other neurodegenerative diseases. The proteins are intrinsically aggregate-prone and form non-amyloid inclusions in the affected nervous tissues, but the role of these proteinaceous aggregates in disease onset and progression is still uncertain. To address this question, we designed a variant of FUS, FUS 1–359, which is predominantly cytoplasmic, highly aggregate-prone, and lacks a region responsible for RNA recognition and binding. Expression of FUS 1–359 in neurons of transgenic mice, at a level lower than that of endogenous FUS, triggers FUSopathy associated with severe damage of motor neurons and their axons, neuroinflammatory reaction, and eventual loss of selective motor neuron populations. These pathological changes cause abrupt development of a severe motor phenotype at the age of 2.5–4.5 months and death of affected animals within several days of onset. The pattern of pathology in transgenic FUS 1–359 mice recapitulates several key features of human ALS with the dynamics of the disease progression compressed in line with shorter mouse lifespan. Our data indicate that neuronal FUS aggregation is sufficient to cause ALS-like phenotype in transgenic mice. 相似文献
72.
Blending disciplines can be transformative in science, yet interdisciplinary mergers should not escape healthy skepticism. Indeed, the history of biology shows us that debates about the relative importance of nuclear genetics vs. microbial symbiosis in eukaryotic biology are among the most engaging. Today's technology may help resolve this century old debate as it illuminates the interwoven genomics and functions of symbionts with their host genome. Thus, we can now assert that all subdisciplines of zoology require microbiology. Although controversial to some, the evidence from studies of host-associated microbial communities indicates that metazoans are hologenomes – interconnected compositions of animal and microbes. 相似文献
73.
Christoph Scherber David J. Gladbach Karen Stevnbak Rune Juelsborg Karsten Inger Kappel Schmidt Anders Michelsen Kristian Rost Albert Klaus Steenberg Larsen Teis Nørgaard Mikkelsen Claus Beier Søren Christensen 《Ecology and evolution》2013,3(6):1449-1460
The impact of climate change on herbivorous insects can have far‐reaching consequences for ecosystem processes. However, experiments investigating the combined effects of multiple climate change drivers on herbivorous insects are scarce. We independently manipulated three climate change drivers (CO2, warming, drought) in a Danish heathland ecosystem. The experiment was established in 2005 as a full factorial split‐plot with 6 blocks × 2 levels of CO2 × 2 levels of warming × 2 levels of drought = 48 plots. In 2008, we exposed 432 larvae (n = 9 per plot) of the heather beetle (Lochmaea suturalis Thomson ), an important herbivore on heather, to ambient versus elevated drought, temperature, and CO2 (plus all combinations) for 5 weeks. Larval weight and survival were highest under ambient conditions and decreased significantly with the number of climate change drivers. Weight was lowest under the drought treatment, and there was a three‐way interaction between time, CO2, and drought. Survival was lowest when drought, warming, and elevated CO2 were combined. Effects of climate change drivers depended on other co‐acting factors and were mediated by changes in plant secondary compounds, nitrogen, and water content. Overall, drought was the most important factor for this insect herbivore. Our study shows that weight and survival of insect herbivores may decline under future climate. The complexity of insect herbivore responses increases with the number of combined climate change drivers. 相似文献
74.
Stroke is a leading cause of death, disability, and socioeconomic loss worldwide. The majority of all strokes result from an interruption in blood flow (ischemia) 1. Middle cerebral artery (MCA) delivers a great majority of blood to the lateral surface of the cortex 2, is the most common site of human stroke 3, and ischemia within its territory can result in extensive dysfunction or death 1,4,5. Survivors of ischemic stroke often suffer loss or disruption of motor capabilities, sensory deficits, and infarct. In an effort to capture these key characteristics of stroke, and thereby develop effective treatment, a great deal of emphasis is placed upon animal models of ischemia in MCA.Here we present a method of permanently occluding a cortical surface blood vessel. We will present this method using an example of a relevant vessel occlusion that models the most common type, location, and outcome of human stroke, permanent middle cerebral artery occlusion (pMCAO). In this model, we surgically expose MCA in the adult rat and subsequently occlude via double ligature and transection of the vessel. This pMCAO blocks the proximal cortical branch of MCA, causing ischemia in all of MCA cortical territory, a large portion of the cortex. This method of occlusion can also be used to occlude more distal portions of cortical vessels in order to achieve more focal ischemia targeting a smaller region of cortex. The primary disadvantages of pMCAO are that the surgical procedure is somewhat invasive as a small craniotomy is required to access MCA, though this results in minimal tissue damage. The primary advantages of this model, however, are: the site of occlusion is well defined, the degree of blood flow reduction is consistent, functional and neurological impairment occurs rapidly, infarct size is consistent, and the high rate of survival allows for long-term chronic assessment. 相似文献
75.
Sakine Simsekyilmaz Fabian Schreiber Stefan Weinandy Felix Gremse Tolga Taha S?nmez Elisa A. Liehn 《Journal of visualized experiments : JoVE》2013,(75)
Despite the considerable progress made in the stent development in the last decades, cardiovascular diseases remain the main cause of death in western countries. Beside the benefits offered by the development of different drug-eluting stents, the coronary revascularization bears also the life-threatening risks of in-stent thrombosis and restenosis. Research on new therapeutic strategies is impaired by the lack of appropriate methods to study stent implantation and restenosis processes. Here, we describe a rapid and accessible procedure of stent implantation in mouse carotid artery, which offers the possibility to study in a convenient way the molecular mechanisms of vessel remodeling and the effects of different drug coatings. 相似文献
76.
77.
The promyelocytic leukemia (PML) protein is a tumor suppressor factor mostly known by its involvement in acute promyelocytic leukemia (APL). Interestingly, recent studies have provided evidence that, in the central nervous system, PML is involved in neurogenesis. However, prospective studies of PML in brain are lacking. To further understand the role of PML in the mammalian brain, we studied plasticity and behavioral changes in PML knockout mice. If PML is involved in neurogenesis, and neurogenesis is an important process for proper brain development as well as learning and memory functions, we hypothesized that PML might have a role in plasticity and cognition. Behavioral studies demonstrated that PML knockout mice present abnormalities in conditioned learning and spatial memory, as determined by fear conditioning and Morris water maze tasks. Experiments to determine normal exploratory behavior interestingly revealed that PML knockout mice present reduced anxiety‐related responses as compared to control animals. This was confirmed when PML knockout mice spent more time in the open arms of an elevated plus‐maze, which is an indication of decreased anxiety. Additionally, impairments in hippocampus‐dependent learning were mirrored by altered long‐term plasticity at Schaffer collateral‐CA1 synapses. We now provide the first evidence for an important role of PML in the brain, indicating that PML might have a role in synaptic plasticity and associated behavioral processes. 相似文献
78.
Matthew R. Heintz Grace A. Fuller Sarah J. Woodhouse Anna Murray Stephanie M. Allard 《Journal of applied animal welfare science : JAAWS》2013,16(4):329-341
As nonhuman animals age, geriatric individuals require additional care and veterinary support to ensure their well being. The focus on lifelong care is a relatively newer approach when providing good welfare, and few studies have examined how veterinary care impacts behavior at different ages or how best to accommodate geriatric individuals in zoos. The objectives of this study were to (a) assess both the immediate and long-term (one year later) behavioral impacts of cataract removal for macaroni (Eudyptes chrysolophus) and southern rockhopper (Eudyptes chrysocome) penguins; (b) compare the behavior of penguins following cataract surgery to that of other conspecifics in the same habitat; and (c) monitor the impacts of cataract surgery on swimming behavior using time-depth recorders. Individual responses to cataract removal differed in direction and magnitude, and these mixed results highlight that welfare is experienced and thus measured at the individual level. Positive responses included increased habitat use, increased time spent swimming, and increased rates of affiliative interactions. This study highlights the importance of assessing welfare impacts of veterinary interventions on geriatric individuals. 相似文献
79.
Field studies of community assembly patterns increasingly use phylogenetic relatedness as a surrogate for traits. Recent experiments appear to validate this approach by showing effects of correlated trait and phylogenetic distances on coexistence. However, traits governing resource use in animals are often labile. To test whether feeding trait or phylogenetic diversity can predict competition and production in communities of grazing amphipods, we manipulated both types of diversity independently in mesocosms. We found that increasing the feeding trait diversity of the community increased the number of species coexisting, reduced dominance and changed food availability. In contrast, phylogenetic diversity had no effect, suggesting that whatever additional ecological information it represents was not relevant in this context. Although community phylogenetic structure in the field may result from multiple traits with potential for phylogenetic signal, phylogenetic effects on species interactions in controlled experiments may depend on the lability of fewer key traits. 相似文献
80.
Keunhee Oh Myung Won Seo Ga Young Lee Ok-Jin Byoun Hye-Ryun Kang Sang-Heon Cho Dong-Sup Lee 《Respiratory research》2013,14(1):35