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排序方式: 共有274条查询结果,搜索用时 234 毫秒
1.
Shreaya Chakroborty Clark Briggs Megan B. Miller Ivan Goussakov Corinne Schneider Joyce Kim Jaime Wicks Jill C. Richardson Vincent Conklin Benjamin G. Cameransi Grace E. Stutzmann 《PloS one》2012,7(12)
Alzheimer’s disease (AD) is a devastating neurodegenerative condition with no known cure. While current therapies target late-stage amyloid formation and cholinergic tone, to date, these strategies have proven ineffective at preventing disease progression. The reasons for this may be varied, and could reflect late intervention, or, that earlier pathogenic mechanisms have been overlooked and permitted to accelerate the disease process. One such example would include synaptic pathology, the disease component strongly associated with cognitive impairment. Dysregulated Ca2+ homeostasis may be one of the critical factors driving synaptic dysfunction. One of the earliest pathophysiological indicators in mutant presenilin (PS) AD mice is increased intracellular Ca2+ signaling, predominantly through the ER-localized inositol triphosphate (IP3) and ryanodine receptors (RyR). In particular, the RyR-mediated Ca2+ upregulation within synaptic compartments is associated with altered synaptic homeostasis and network depression at early (presymptomatic) AD stages. Here, we offer an alternative approach to AD therapeutics by stabilizing early pathogenic mechanisms associated with synaptic abnormalities. We targeted the RyR as a means to prevent disease progression, and sub-chronically treated AD mouse models (4-weeks) with a novel formulation of the RyR inhibitor, dantrolene. Using 2-photon Ca2+ imaging and patch clamp recordings, we demonstrate that dantrolene treatment fully normalizes ER Ca2+ signaling within somatic and dendritic compartments in early and later-stage AD mice in hippocampal slices. Additionally, the elevated RyR2 levels in AD mice are restored to control levels with dantrolene treatment, as are synaptic transmission and synaptic plasticity. Aβ deposition within the cortex and hippocampus is also reduced in dantrolene-treated AD mice. In this study, we highlight the pivotal role of Ca2+ aberrations in AD, and propose a novel strategy to preserve synaptic function, and thereby cognitive function, in early AD patients. 相似文献
2.
Background
Micro-biological research relies on the use of model organisms that act as representatives of their species or subspecies, these are frequently well-characterized laboratory strains. However, it has often become apparent that the model strain initially chosen does not represent important features of the species. For micro-organisms, the diversity of their genomes is such that even the best possible choice of initial strain for sequencing may not assure that the genome obtained adequately represents the species. To acquire information about a species' genome as efficiently as possible, we require a method to choose strains for analysis on the basis of how well they represent the species. 相似文献3.
Replacement of the invariant lysine 77 by arginine in yeast iso-1-cytochrome c results in enhanced and normal activities in vitro and in vivo 总被引:10,自引:0,他引:10
D Holzschu L Principio K T Conklin D R Hickey J Short R Rao G McLendon F Sherman 《The Journal of biological chemistry》1987,262(15):7125-7131
Oligonucleotide-directed mutagenesis of the yeast Saccharomyces cerevisiae was used to generate an abnormal iso-1-cytochrome c having an Arg-77 replacement of the normal Lys-77; this Lys-77 residue is evolutionarily conserved in most eukaryotic cytochromes c and is trimethylated in fungal and plant cytochromes c. Examination of strains having a single chromosomal copy of the gene encoding the Arg-77 protein indicated that the altered protein was synthesized at the normal rate and that it had normal or near normal activity in vivo. Examination of enzymatic activities in vitro with cytochrome b2, cytochrome c peroxidase, and cytochrome c oxidase indicated that the altered iso-1-cytochrome c has equal or enhanced catalytic efficiencies. Thus, replacement of the evolutionarily conserved residue Lys-77 produces no or only minor effects both in vivo and in vitro. 相似文献
4.
Carbachol-induced reverse transformation of Chinese hamster ovary cells transfected with and expressing the m5 muscarinic acetylcholine receptor 总被引:2,自引:0,他引:2
Reverse transformation was induced in Chinese hamster ovary (CHO) cells transfected with and stably expressing the m5 subtype of the muscarinic acetylcholine receptor when stimulated with the muscarinic agonist, carbachol. Atropine, a muscarinic antagonist, blocked the carbachol-stimulated reverse transformation. CHO cells not transfected with the muscarinic receptor did not change with added carbachol. PMA induced reverse transformation without increasing cAMP accumulation in CHO cells. Carbachol, prostaglandin E2, and cholecystokinin increased cAMP accumulation but only carbachol caused reverse transformation. Carbachol-stimulated cAMP accumulation occurred at a higher concentration (EC50 10 microM) than did carbachol-stimulated reverse transformation (EC50 63 nM). Muscarinic m5 acetylcholine receptor transfected into CHO cells can induce reverse transformation which may be independent of cAMP. 相似文献
5.
6.
Identification of a Putative Structural Gene for Cathepsin D in Caenorhabditis Elegans 总被引:2,自引:0,他引:2
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L. A. Jacobson L. Jen-Jacobson J. M. Hawdon G. P. Owens M. A. Bolanowski S. W. Emmons M. V. Shah R. A. Pollock D. S. Conklin 《Genetics》1988,119(2):355-363
Mutants of Caenorhabditis elegans having about 10% of wild-type activity of the aspartyl protease cathepsin D have been isolated by screening. Mutant homozygotes have normal growth rates and no obvious morphological or developmental abnormalities. The mutant gene (cad-1) has been mapped to the right extremity of linkage group II. Heterozygous animals (cad-1/+) show intermediate enzyme levels and animals heterozygous for chromosomal deficiencies of the right extremity of linkage group II have 50% of wild-type activity. Cathepsin D purified from a mutant strain has a lower activity per unit mass of pure enzyme. These data suggest that cad-1 is a structural gene for cathepsin D. 相似文献
7.
8.
Daniel G. Doughtie Philip J. Conklin K.Ranga Rao 《Journal of invertebrate pathology》1983,42(2):249-258
Adult grass shrimp were exposed to four concentrations (0.5, 1.0, 2.0 and 4.0 ppm) of hexavalent chromium for 28 days. At the end of the exposure period, over 50% of the surviving shrimp possessed cuticular lesions that had many of the gross characteristics of “shell disease.” These lesions were usually associated with articulations of the appendages and abdomen. Furthermore, it was found that at increasing levels of chromium exposure, there was a proportionate increase in the loss of limbs such that nearly 50% of the limbs were lost in grass shrimp exposed to the highest test concentration of chromium. Histological and ultrastructural examination of numerous lesions demonstrated a range of degenerative features within the subcuticular epithelium that included cytoplasmic vacuolization, mitochondrial swelling, chromatin emargination, and the presence of unusual nuclear inclusions that appear to indicate direct chromium toxicity. Additionally, a marked retardation in new epicuticle and exocuticle formation was observed in viable tissues associated with lesions in late premolt shrimp. It is proposed that chromium interferes with the normal functions of subcuticular epithelium, particularly cuticle formation, and subsequently causes structural weaknesses or perforations to develop in the cuticle of newly moted shrimp. Because of these chromium-induced exoskeletal deficiencies, a viaduct for pathogenic organisms (e.g., bacteria) and direct chromium influx is formed that perpetuates lesion development. 相似文献
9.
D. J. Conklin H. B. Lillywhite K. R. Olson R. E. Ballard A. R. Hargens 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1996,165(7):518-526
The effects of vasoactive agonists on systemic blood vessels were examined with respect to anatomical location and gravity acclimation in the semi-arboreal snake, Elaphe Obsoleta. Major blood vessels were reactive to putative neurotransmitters, hormones or local factors in vessel specific patterns. Catecholamines, adenosine triphosphate, histamine and high potassium (80 mM) stimulated significantly greater tension per unit vessel mass in posterior than anterior arteries. Anterior vessels were significantly more sensitive to catecholamines than midbody and posterior vessels. Angiotensin II stimulated significantly greater tension in carotid artery than in midbody and posterior dorsal aorta. Arginine vasotocin strongly contracted the left and right aortic arches and anterior dorsal aorta. Veins were strongly contracted by catecholamines, high potassium and angiotensin II, but less so by adenosine triphosphate, arginine vasotocin and histamine. Precontracted vessels were relaxed by acetylcholine and sodium nitroprusside, but not by atrial natriuretic peptide or bradykinin. Chronic exposure of snakes to intermittent hypergravity stress (+1.5 Gz at tail) did not affect the majority of vessel responses. These data demonstrate that in vitro tension correlates with known patterns of sympathetic innervation and suggest that catecholamines, as well as other agonists, are important in mediating vascular responses to gravitational stresses in snakes.Abbreviations
ACH
acetylcholine
-
ADA
anterior dorsal aorta
-
ANG II
salmon asn1-val5-angiotensin II
-
ANP
rat ile26-atrial natriuretic peptide
-
ATP
adenosine triphosphate
-
AVT
arginine vasotocin
-
BK
human bradykinin
-
BL
total body length
-
CA
carotid artery
-
CONT
control
-
EC
50
effective concentration producing 50% maximal response
-
EPI
epinephrine
- + G
z
earth's gravity force
-
HI-G
high gravity acclimation
-
HI K
+
80 mM high potassium
-
JV
jugular vein
-
LAA
left aortic arch
-
MDA
midbody dorsal aorta
-
MPV
midbody portal vein
-
MS
Mackenzie's solution
-
NEPI
norepinephrine
-
pD
2
log EC50
-
PDA
posterior dorsal aorta
-
PPV
posterior portal vein
-
RAA
right aortic arch
-
SNP
sodium nitroprusside 相似文献
10.
G. Mattson E. Conklin S. Desai G. Nielander M. D. Savage S. Morgensen 《Molecular biology reports》1993,17(3):167-183
The various aspects of chemical crosslinking are addressed. Crosslinker reactivity, specificity, spacer arm length and solubility characteristics are detailed. Considerations for choosing one of these crosslinkers for a particular application are given as well as reaction conditions and practical tips for use of each category of crosslinkers.Abbreviations ABH
azidobenzoyl hydrazide
- ANB- NOS
N-5-azido-2-nitrobenzoyloxysuccinimide
- ASIB
1-(p-azidosalicylamido)-4-(iodoacetamido)butane
- ASBA
4-(p-azidosalicylamido)butylamine
- APDP
N-[4-(p-azidosalicylamido) butyl]-3(2-pyridyldithio)propionamide
- APG
p-azidophenyl glyoxal monohydrate
- BASED
bis-[-(4-azidosalicylamido)ethyl] disulfide
- BMH
bismaleimidohexane
- BS3
bis(sulfosuccinimidyl) suberate
- BSOCOES
bis[2-(succinimidooxycarbonyloxy)ethyl]sulfone
- DCC
N,N-dicyclohexylcarbodiimide
- DFDNB
1,5-difluoro-2,4-dinitrobenzene
- DMA
dimethyl adipimidate·2HCl
- DMP
dimethyl pimelimidate·2HCl
- DMS
dimethyl suberimidate·2HCl
- DPDPB
1,4-di-(3,2-pyridyldithio)propionamido butane
- DMF
dimethylformamide
- DMSO
dimethylsulfoxide
- DSG
disuccinimidyl glutarate
- DSP
dithiobis(succinimidylpropionate)
- DSS
disuccinimidyl suberate
- DST
disuccinimidyl tartarate
- DTSSP
3,3-dithiobis (sulfosuccinimidylpropionate)
- DTBP
dimethyl 3,3-dithiobispropionimidate·2HCl
- EDC or EDAC
1-ethyl-3-(3-dimethylaminopropyl)carbodimide hydrochloride
- EDTA
ethylenediaminetetraacetic acid disodium salt, dihydrate
- EGS
ethylene glycolbis(succinimidylsuccinate)
- GMBS
N--maleimidobutyryloxysuccinimide ester
- HSAB
N-hydroxysuccinimidyl-4-azidobenzoate
- HEPES
4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid
- MBS
m-maleimidobenzoyl-N-hydroxysuccinimide ester
- MES
4-morpholineethanesulfonic acid
- NHS
N-hydroxysuccinimide
- NHS-ASA
N-hydroxysuccinimidyl-4-azidosalicylic acid
- PMFS
phenylmethylsulfonyl fluoride
- PNP-DTP
p-nitrophenyl-2-diazo-3,3,3-trifluoropropionate
- SAED
sulfosuccinimidyl 2-(7-azido-4-methylcoumarin-3-acetamide) ethyl-1,3-dithiopropionate
- SADP
N-succinimdyl (4-azidophenyl)1,3-dithiopropionate
- SAND
sulfosuccinimidyl 2-(m-azido-o-nitrobenzamido)-ethyl-1,3-dithiopropionate
- SANPAH
N-succinimidyl-6(4-azido-2-nitrophenyl-amino)hexanoate
- SASD
sulfosuccinimidyl 2-(p-azidosalicylamido)ethyl-1,3-dithiopropionate
- SATA
N-succinimidyl-S-acetylthioacetate
- SDBP
N-hydroxysuccinimidyl-2,3-dibromopropionate
- SIAB
N-succinimidyl(4-iodoacetyl)aminobenzoate
- SMCC
succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate
- SMPB
succinimidyl 4-(p-maleimidophenyl) butyrate
- SMPT
4-succinimidyloxycarbonyl--methyl--(2-pyridyldithio)-toluene
- sulfo-BSOCOES
bis[2-sulfosuccinimidooxycarbonyloxy) ethyl]sulfone
- sulfo-DST
disulfosuccinimidyl tartarate
- sulfo-EGS
ethylene glycolbis(sulfosuccinimidylsuccinate)
- sulfo-GMBS
N--maleimidobutyryloxysulfosuccinimide ester
- sulfo-MBS
m-maleimidobenzoyl-N-hydroxysulfosuccinimide ester
- sulfo-SADP
sulfosuccinimidyl(4-azidophenyldithio)propionate
- sulfo-SAMCA
sulfosuccinimidyl 7-azido-4-methylcoumarin-3-acetate
- sulfo-SANPAH
sulfosuccinimidyl 6-(4-azido-2-nitrophenylamino)hexanoate
- sulfo-SIAB
sulfosuccinimidyl(4-iodoacetyl)aminobenzoate
- sulfo-SMPB
sulfo-succinimidyl 4-(p-maleimidophenyl)butyrate
- sulfo-SMCC
sulfosuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate
- SPDP
N-succinimidyl 3-(2-pyridyldithio)propionate 相似文献