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31.
Fontainhas AM Wang M Liang KJ Chen S Mettu P Damani M Fariss RN Li W Wong WT 《PloS one》2011,6(1):e15973
Purpose
Microglia represent the primary resident immune cells in the CNS, and have been implicated in the pathology of neurodegenerative diseases. Under basal or “resting” conditions, microglia possess ramified morphologies and exhibit dynamic surveying movements in their processes. Despite the prominence of this phenomenon, the function and regulation of microglial morphology and dynamic behavior are incompletely understood. We investigate here whether and how neurotransmission regulates “resting” microglial morphology and behavior.Methods
We employed an ex vivo mouse retinal explant system in which endogenous neurotransmission and dynamic microglial behavior are present. We utilized live-cell time-lapse confocal imaging to study the morphology and behavior of GFP-labeled retinal microglia in response to neurotransmitter agonists and antagonists. Patch clamp electrophysiology and immunohistochemical localization of glutamate receptors were also used to investigate direct-versus-indirect effects of neurotransmission by microglia.Results
Retinal microglial morphology and dynamic behavior were not cell-autonomously regulated but are instead modulated by endogenous neurotransmission. Morphological parameters and process motility were differentially regulated by different modes of neurotransmission and were increased by ionotropic glutamatergic neurotransmission and decreased by ionotropic GABAergic neurotransmission. These neurotransmitter influences on retinal microglia were however unlikely to be directly mediated; local applications of neurotransmitters were unable to elicit electrical responses on microglia patch-clamp recordings and ionotropic glutamatergic receptors were not located on microglial cell bodies or processes by immunofluorescent labeling. Instead, these influences were mediated indirectly via extracellular ATP, released in response to glutamatergic neurotransmission through probenecid-sensitive pannexin hemichannels.Conclusions
Our results demonstrate that neurotransmission plays an endogenous role in regulating the morphology and behavior of “resting” microglia in the retina. These findings illustrate a mode of constitutive signaling between the neural and immune compartments of the CNS through which immune cells may be regulated in concert with levels of neural activity. 相似文献32.
Retinal pigment epithelium response to oxidant injury in the pathogenesis of early age-related macular degeneration 总被引:1,自引:0,他引:1
Age-related macular degeneration (AMD) represents the leading cause of vision loss in the elderly. Accumulation of lipid- and protein-rich deposits under the retinal pigment epithelium (RPE) heralds the onset of early AMD, but the pathogenesis of subretinal deposit formation is poorly understood. Numerous hypothetical models of deposit formation have been proposed, including hypotheses for a genetic basis, choroidal hypoperfusion, abnormal barrier formation, and lysosomal failure. This review explore the RPE injury hypothesis, characterized by three distinct stages (1) Initial RPE oxidant injury, caused by any number of endogenous or exogenous oxidants, results in extrusion of cell membrane "blebs," together with decreased activity of matrix metalloproteinases (MMPs), promoting bleb accumulation under the RPE as basal laminar deposits (BLD). (2) RPE cells are subsequently stimulated to increase synthesis of MMPs and other molecules responsible for extracellular matrix turnover (i.e., producing decreased collagen), affecting both RPE basement membrane and Bruchs membrane (BrM). This process leads to progression of BLD into basal linear deposits (BLinD) and drusen by admixture of blebs into BrM, followed by the formation of new basement membrane under the RPE to trap these deposits within BrM. We postulate that various hormones and other plasma-derived molecules related to systemic health cofactors are implicated in this second stage. (3) Finally, macrophages are recruited to sites of RPE injury and deposit formation. The recruitment of nonactivated or scavenging macrophages may remove deposits without further injury, while the recruitment of activated or reparative macrophages, through the release of inflammatory mediators, growth factors, or other substances, may promote complications and progression to the late forms of the disease. 相似文献
33.
The orthocladiine Chironomidae genus Stictocladius Edwards was described originally from South America. Although recognised subsequently as present also in Australia and New Zealand, the true diversity in the Neotropics has remained unclear. After more than a decade of collections of both isolated adults and aquatic immature stages, we can recognise several new taxa and associate some immature stages. Thus, we describe Stictocladius prati n. sp. as male, female, pupa and larva; Stictocladius acutus n. sp. and Stictocladius acrilobus n. sp. as male, female and pupa; Stictocladius fimbriatus n. sp. as male and female; Stictocladius fovigus n. sp. and Stictocladius nudiventer n. sp. as male and pupa; and Stictocladius privicalcar n. sp. and Stictocladius prostatus n. sp. each as male imago alone. The male and female of Stictocladius pulchripennis Edwards is redescribed and the pupa described. The male and female of Stictocladius flavozonatus Edwards and the male of Stictocladius calonotum Edwards are described. Five pupal types are described: Stictocladius sp. A (near S. acrilobus), Stictocladius sp. B (possibly S. calonotum), Stictocladius sp. C (near S. calonotum), Stictocladius sp. D (possibly S. flavozonatus) and Stictocladius sp. E with uncertain affinity. A larva from Chile of the Stictocladius ??sofour type?? (Stictocladius sp. F) and an unreared larva from North America (Stictocladius sp. G) possibly belonging to S. acutus are described. Keys to named Neotropical male and female imagines of Stictocladius and to all pupal forms of Neotropical Stictocladius are provided. Some data concerning fourth instars of Stictocladius are presented. Means of differentiation from putative sister taxon Lopescladius are discussed. 相似文献
34.
This essay complements that de Baat et al1 in the last issue with emphasis on the importance of the variability between individual older people. The consequent need for an open minded approach towards planning Prosthodontics is discussed, based on each patient's motivation for aesthetics, function, comfort and self esteem. Both functional expectations and motivation to learn effective health behaviour vary widely, and evaluation of both is essential for realistic planning because further tooth loss and the need for partial dentures occur so frequently. The consequent variation in plans raises the question – which are the strategic teeth to maintain a stable dental occlusion or a future tooth stabilised denture? For undergraduates this demands a non-rote approach to learning. 相似文献
35.
Background
Severe cardiotoxicity is a documented, but very unusual side-effect of intravenous 5-fluorouracil therapy. The mechanism producing cardiotoxicity is poorly understood. 相似文献36.
Background
Specification of primordial germ cells in mice depends on instructive signalling events, which act first to confer germ cell competence on epiblast cells, and second, to impose a germ cell fate upon competent precursors. fragilis, an interferon-inducible gene coding for a transmembrane protein, is the first gene to be implicated in the acquisition of germ cell competence. 相似文献37.
38.
Ediriweera PS Chandana Yasuhiro Maeda Akihiko Ueda Hiroshi Kiyonari Naoko Oshima Mako Yamamoto Shunya Kondo Junseo Oh Rei Takahashi Yoko Yoshida Satoshi Kawashima David B Alexander Hitoshi Kitayama Chiaki Takahashi Yasuhiko Tabata Tomoko Matsuzaki Makoto Noda 《BMC developmental biology》2010,10(1):1-13
Background
The accessibility of the developing zebrafish pharyngeal dentition makes it an advantageous system in which to study many aspects of tooth development from early initiation to late morphogenesis. In mammals, hedgehog signaling is known to be essential for multiple stages of odontogenesis; however, potential roles for the pathway during initiation of tooth development or in later morphogenesis are incompletely understood.Results
We have identified mRNA expression of the hedgehog ligands shha and the receptors ptc1 and ptc2 during zebrafish pharyngeal tooth development. We looked for, but did not detect, tooth germ expression of the other known zebrafish hedgehog ligands shhb, dhh, ihha, or ihhb, suggesting that as in mammals, only Shh participates in zebrafish tooth development. Supporting this idea, we found that morphological and gene expression evidence of tooth initiation is eliminated in shha mutant embryos, and that morpholino antisense oligonucleotide knockdown of shha, but not shhb, function prevents mature tooth formation. Hedgehog pathway inhibition with the antagonist compound cyclopamine affected tooth formation at each stage in which we applied it: arresting development at early stages and disrupting mature tooth morphology when applied later. These results suggest that hedgehog signaling is required continuously during odontogenesis. In contrast, over-expression of shha had no effect on the developing dentition, possibly because shha is normally extensively expressed in the zebrafish pharyngeal region.Conclusion
We have identified previously unknown requirements for hedgehog signaling for early tooth initiation and later morphogenesis. The similarity of our results with data from mouse and other vertebrates suggests that despite gene duplication and changes in the location of where teeth form, the roles of hedgehog signaling in tooth development have been largely conserved during evolution. 相似文献39.
René J van der Schaaf Bimmer E Claessen Loes P Hoebers Niels J Verouden Jacques J Koolen Maarten J Suttorp Emanuele Barbato Matthijs Bax Bradley H Strauss Göran K Olivecrona Vegard Tuseth Dietmar Glogar Truls Råmunddal Jan G Tijssen Jan J Piek José PS Henriques 《Trials》2010,11(1):1-9
Background
Hypothyroidism is a prevalent endocrine condition. Individuals with this disease are commonly managed through supplementation with synthetic thyroid hormone, with the aim of alleviating symptoms and restoring normal thyroid stimulating hormone levels. Generally this management strategy is effective and well tolerated. However, there is research to suggest that a significant proportion of hypothyroid sufferers are being inadequately managed. Furthermore, hypothyroid patients are more likely to have a decreased sense of well-being and more commonly experience constitutional and neuropsychiatric complaints, even with pharmacological intervention. The current management of hypothyroidism follows a biomedical model. Little consideration has been given to a biopsychosocial approach to this condition. Within the chiropractic profession there is growing support for the use of a biopsychosocial-based intervention called Neuro-Emotional Technique (NET) for this population.Methods/Design
A placebo-controlled, single-blinded, randomised clinical pilot-trial has been designed to assess the influence of Neuro-Emotional Technique on a population with primary overt hypothyroidism. A sample of 102 adults (≥18 years) who meet the inclusion criteria will be randomised to either a treatment group or a placebo group. Each group will receive ten treatments (NET or placebo) over a six week period, and will be monitored for six months. The primary outcome will involve the measurement of depression using the Depression, Anxiety and Stress Scale (DASS). The secondary outcome measures to be used are; serum thyroid stimulating hormone, serum free-thyroxine, serum free-triiodothyronine, serum thyroid peroxidase auto-antibodies, serum thyroglobulin auto-antibodies as well as the measurement of functional health and well-being using the Short-Form-36 Version 2. The emotional states of anxiety and stress will be measured using the DASS. Self-measurement of basal heart rate and basal temperature will also be included among the secondary outcome measures. The primary and secondary measures will be obtained at commencement, six weeks and six months. Measures of basal heart rate and basal temperature will be obtained daily for the six month trial period, with recording to commence one week prior to the intervention.Discussion
The study will provide information on the influence of NET when added to existing management regimens in individuals with primary overt hypothyroidism.Trial Registration
ANZCTR Number: 12607000040460 相似文献40.