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排序方式: 共有378条查询结果,搜索用时 31 毫秒
31.
Brett M. Macey Matthew J. Jenny Heidi R. Williams Lindy K. Thibodeaux Marion Beal Jonas S. Almeida Charles Cunningham Annalaura Mancia Gregory W. Warr Erin J. Burge A. Fred Holland Paul S. Gross Sonomi Hikima Karen G. Burnett Louis Burnett Robert W. Chapman 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2010,155(3):341-349
Heavy metals, such as copper, zinc and cadmium, represent some of the most common and serious pollutants in coastal estuaries. In the present study, we used a combination of linear and artificial neural network (ANN) modelling to detect and explore interactions among low-dose mixtures of these heavy metals and their impacts on fundamental physiological processes in tissues of the Eastern oyster, Crassostrea virginica. Animals were exposed to Cd (0.001–0.400 μM), Zn (0.001–3.059 μM) or Cu (0.002–0.787 μM), either alone or in combination for 1 to 27 days. We measured indicators of acid–base balance (hemolymph pH and total CO2), gas exchange (Po2), immunocompetence (total hemocyte counts, numbers of invasive bacteria), antioxidant status (glutathione, GSH), oxidative damage (lipid peroxidation; LPx), and metal accumulation in the gill and the hepatopancreas. Linear analysis showed that oxidative membrane damage from tissue accumulation of environmental metals was correlated with impaired acid–base balance in oysters. ANN analysis revealed interactions of metals with hemolymph acid–base chemistry in predicting oxidative damage that were not evident from linear analyses. These results highlight the usefulness of machine learning approaches, such as ANNs, for improving our ability to recognize and understand the effects of sub-acute exposure to contaminant mixtures. 相似文献
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33.
Vera MF da Silva Anthony M Carter Carlos E Ambrosio Ana F Carvalho Marina Bonatelli Marcelo C Lima Angelica Maria Miglino 《Reproductive biology and endocrinology : RB&E》2007,5(1):26-6
A recent reassessment of the phylogenetic affinities of cetaceans makes it timely to compare their placentation with that
of the artiodactyls. We studied the placentae of two sympatric species of dolphin from the Amazon River Basin, representing
two distinct families. The umbilical cord branched to supply a bilobed allantoic sac. Small blood vessels and smooth muscle
bundles were found within the stroma of the cord. Foci of squamous metaplasia occurred in the allanto-amnion and allantochorion.
The interhemal membrane of the placenta was of the epitheliochorial type. Two different types of trophoblastic epithelium
were seen. Most was of the simple columnar type and indented by fetal capillaries. However, there were also areolar regions
with tall columnar trophoblast and these were more sparsely supplied with capillaries. The endometrium was well vascularised
and richly supplied with actively secreting glands. These findings are consistent with the current view that Cetacea are nested
within Artiodactyla as sister group to the hippopotamids. 相似文献
34.
Kelly J. Phelps Kiet Tran Tristan Eifler Anna I. Erickson Andrew J. Fisher Peter A. Beal 《Nucleic acids research》2015,43(2):1123-1132
Adenosine deaminases acting on RNA (ADARs) hydrolytically deaminate adenosines (A) in a wide variety of duplex RNAs and misregulation of editing is correlated with human disease. However, our understanding of reaction selectivity is limited. ADARs are modular enzymes with multiple double-stranded RNA binding domains (dsRBDs) and a catalytic domain. While dsRBD binding is understood, little is known about ADAR catalytic domain/RNA interactions. Here we use a recently discovered RNA substrate that is rapidly deaminated by the isolated human ADAR2 deaminase domain (hADAR2-D) to probe these interactions. We introduced the nucleoside analog 8-azanebularine (8-azaN) into this RNA (and derived constructs) to mechanistically trap the protein–RNA complex without catalytic turnover for EMSA and ribonuclease footprinting analyses. EMSA showed that hADAR2-D requires duplex RNA and is sensitive to 2′-deoxy substitution at nucleotides opposite the editing site, the local sequence and 8-azaN nucleotide positioning on the duplex. Ribonuclease V1 footprinting shows that hADAR2-D protects ∼23 nt on the edited strand around the editing site in an asymmetric fashion (∼18 nt on the 5′ side and ∼5 nt on the 3′ side). These studies provide a deeper understanding of the ADAR catalytic domain–RNA interaction and new tools for biophysical analysis of ADAR–RNA complexes. 相似文献
35.
Beal MF 《Amino acids》2011,40(5):1305-1313
There is a substantial body of literature, which has demonstrated that creatine has neuroprotective effects both in vitro
and in vivo. Creatine can protect against excitotoxicity as well as against β-amyloid toxicity in vitro. We carried out studies
examining the efficacy of creatine as a neuroprotective agent in vivo. We demonstrated that creatine can protect against excitotoxic
lesions produced by N-methyl-d-aspartate. We also showed that creatine is neuroprotective against lesions produced by the toxins malonate and 3-nitropropionic
acid (3-NP) which are reversible and irreversible inhibitors of succinate dehydrogenase, respectively. Creatine produced dose-dependent
neuroprotective effects against MPTP toxicity reducing the loss of dopamine within the striatum and the loss of dopaminergic
neurons in the substantia nigra. We carried out a number of studies of the neuroprotective effects of creatine in transgenic
mouse models of neurodegenerative diseases. We demonstrated that creatine produced an extension of survival, improved motor
performance, and a reduction in loss of motor neurons in a transgenic mouse model of amyotrophic lateral sclerosis (ALS).
Creatine produced an extension of survival, as well as improved motor function, and a reduction in striatal atrophy in the
R6/2 and the N-171-82Q transgenic mouse models of Huntington’s disease (HD), even when its administration was delayed until
the onset of disease symptoms. We recently examined the neuroprotective effects of a combination of coenzyme Q10 (CoQ10) with
creatine against both MPTP and 3-NP toxicity. We found that the combination of CoQ and creatine together produced additive
neuroprotective effects in a chronic MPTP model, and it blocked the development of alpha-synuclein aggregates. In the 3-NP
model of HD, CoQ and creatine produced additive neuroprotective effects against the size of the striatal lesions. In the R6/2
transgenic mouse model of HD, the combination of CoQ and creatine produced additive effects on improving survival. Creatine
may stabilize mitochondrial creatine kinase, and prevent activation of the mitochondrial permeability transition. Creatine,
however, was still neuroprotective in mice, which were deficient in mitochondrial creatine kinase. Administration of creatine
increases the brain levels of creatine and phosphocreatine. Due to its neuroprotective effects, creatine is now in clinical
trials for the treatment of Parkinson’s disease (PD) and HD. A phase 2 futility trial in PD showed approximately a 50% improvement
in Unified Parkinson’s Disease Rating Scale at one year, and the compound was judged to be non futile. Creatine is now in
a phase III clinical trial being carried out by the NET PD consortium. Creatine reduced plasma levels of 8-hydroxy-2-deoxyguanosine
in HD patients phase II trial and was well-tolerated. Creatine is now being studied in a phase III clinical trial in HD, the
CREST trial. Creatine, therefore, shows great promise in the treatment of a variety of neurodegenerative diseases. 相似文献
36.
Germano Siqueira Adriane MF Milagres Walter Carvalho Gerald Koch André Ferraz 《Biotechnology for biofuels》2011,4(1):7
Background
Lignin and hemicelluloses are the major components limiting enzyme infiltration into cell walls. Determination of the topochemical distribution of lignin and aromatics in sugar cane might provide important data on the recalcitrance of specific cells. We used cellular ultraviolet (UV) microspectrophotometry (UMSP) to topochemically detect lignin and hydroxycinnamic acids in individual fiber, vessel and parenchyma cell walls of untreated and chlorite-treated sugar cane. Internodes, presenting typical vascular bundles and sucrose-storing parenchyma cells, were divided into rind and pith fractions. 相似文献37.
38.
39.
Brownell AL Chen YI Yu M Wang X Dedeoglu A Cicchetti F Jenkins BG Beal MF 《Journal of neurochemistry》2004,89(5):1206-1214
To explore acute and long-term effects of 3-nitropropionic acid (3-NP)-induced neurotoxicity, longitudinal positron emission tomography (PET) studies of energy metabolism and magnetic resonance spectroscopic (MRS) studies of neurochemicals were conducted in a rat model. The first injection of 3-NP (20 mg/kg i.p.) was followed by MRS study of neurochemicals and PET study of glucose utilization using [(18)F]2-fluorodeoxy-D-glucose ((18)F-FDG). After that, 3-NP administration was done two times a day with a dose of 10 mg/kg i.p. until animals were symptomatic or for a maximum of 5 days combined with daily PET studies. Long-term effects were investigated 4 weeks and 4 months after cessation of 3-NP. These studies showed a significant inter-animal variation in response of 3-NP toxicity. Animals that developed large striatal lesions had decreased glucose utilization in the striatum and cortex 1 day after starting 3-NP injections. Similarly succinate and lactate/macromolecule levels were enhanced; these changes being, however, reversible. Progressive degeneration was observed by decreasing striatal glucose utilization and N-acetylaspartate (NAA) and increasing choline. These observations paralleled with weight loss and deficits in behavior. Animals that did not develop lesions showed reversible enhancement in cortical glucose utilization and no change in striatal glucose utilization or neurochemicals or locomotor activity. 相似文献
40.
Controlling activation of the RNA-dependent protein kinase by siRNAs using site-specific chemical modification 总被引:3,自引:0,他引:3
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Puthenveetil S Whitby L Ren J Kelnar K Krebs JF Beal PA 《Nucleic acids research》2006,34(17):4900-4911
The RNA-dependent protein kinase (PKR) is activated by binding to double-stranded RNA (dsRNA). Activation of PKR by short-interfering RNAs (siRNAs) and stimulation of the innate immune response has been suggested to explain certain off-target effects in some RNA interference experiments. Here we show that PKR's kinase activity is stimulated in vitro 3- to 5-fold by siRNA duplexes with 19 bp and 2 nt 3′-overhangs, whereas the maximum activation observed for poly(I)•poly(C) was 17-fold over background under the same conditions. Directed hydroxyl radical cleavage experiments indicated that siRNA duplexes have at least four different binding sites for PKR's dsRNA binding motifs (dsRBMs). The location of these binding sites suggested specific nucleotide positions in the siRNA sense strand that could be modified with a corresponding loss of PKR binding. Modification at these sites with N2-benzyl-2′-deoxyguanosine (BndG) blocked interaction with PKR's dsRBMs and inhibited activation of PKR by the siRNA. Importantly, modification of an siRNA duplex that greatly reduced PKR activation did not prevent the duplex from lowering mRNA levels of a targeted message by RNA interference in HeLa cells. Thus, these studies demonstrate that specific positions in an siRNA can be rationally modified to prevent interaction with components of cellular dsRNA-regulated pathways. 相似文献