排序方式: 共有49条查询结果,搜索用时 406 毫秒
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Annemarie MM Vlaar Angela EP Bouwmans Marinus JPG van Kroonenburgh Werner H Mess Selma C Tromp Piet GWM Wuisman Alfons GH Kessels Ania Winogrodzka Wim EJ Weber 《BMC neurology》2007,7(1):28
Background
Parkinson's disease (PD) is the second most common neurodegenerative disorder. As there is no definitive diagnostic test, its diagnosis is based on clinical criteria. Recently transcranial duplex scanning (TCD) of the substantia nigra in the brainstem has been proposed as an instrument to diagnose PD. We and others have found that TCD scanning of substantia nigra duplex is a relatively accurate diagnostic instrument in patients with parkinsonian symptoms. However, all studies on TCD so far have involved well-defined, later-stage PD patients, which will obviously lead to an overestimate of the diagnostic accuracy of TCD. 相似文献4.
The peroxiredoxins are a ubiquitous family of proteins involved in protection against oxidative stress through the detoxification of cellular peroxides. In addition, the typical 2-Cys peroxiredoxins function in signalling of peroxide stress and as molecular chaperones, functions that are influenced by their oligomeric state. Of the human peroxiredoxins, Prx IV (peroxiredoxin IV) is unique in possessing an N-terminal signal peptide believed to allow secretion from the cell. Here, we present a characterization of Prx IV in human cells demonstrating that it is actually retained within the ER (endoplasmic reticulum). Stable knockdown of Prx IV expression led to detrimental effects on the viability of human HT1080 cells following treatment with exogenous H2O2. However, these effects were not consistent with a dose-dependent correlation between Prx IV expression and peroxide tolerance. Moreover, modulation of Prx IV expression showed no obvious effect on ER-associated stress, redox conditions or H2O2 turnover. Subsequent investigation demonstrated that Prx IV forms complex structures within the ER, consistent with the formation of homodecamers. Furthermore, Prx IV oligomeric interactions are stabilized by additional non-catalytic disulfide bonds, indicative of a primary role other than peroxide elimination. 相似文献
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Abstract. Woodland colonization on wetlands is considered to have a detrimental effect on their ecological value, even though detailed analysis of this process is lacking. This paper provides an evaluation of the ecological changes resulting from succession of poor fen (base‐poor mire) to willow wet woodland on Goss Moor NNR in Cornwall, UK. Different ages of willow carr were associated with eight understorey communities. During willow colonization, in the ground flora, there was a progressive decrease in poor fen species and an associated increase in woodland species, which appeared to be related to an increase in canopy cover and therefore shade. The most diverse community was found to be the most recent willow and was dominated by poor fen species. The oldest willow was the second most diverse and was associated with a reduction in poor fen species and an increase in woodland species. Architectural features were used successfully to assess the general condition and structure of willow. Tree height and DBH were identified as useful parameters to accurately assess willow age in the field. The implications of active intervention to remove willow in order to conserve the full range of communities within the hydrosere are discussed. 相似文献
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BŁAŻEJ BERKOWSKI CHRISTIAN KLUG 《Lethaia: An International Journal of Palaeontology and Stratigraphy》2012,45(1):24-33
Berkowski, B & Klug, C. 2011: Lucky rugose corals on crinoid stems: unusual examples of subepidermal epizoans from the Devonian of Morocco. Lethaia, Vol. 45, pp. 24–33. In the fossil record, evidence for true epizoans, i.e. living animals inhabiting other living host‐animals, is rather rare. A host reaction is usually needed to proof the syn vivo‐settling of the epizoan. Herein, we provide a first report of such an epizoan biocoenosis from various strata of the Early Devonian of Hamar Laghdad, the world‐renowned Moroccan mud‐mound locality. In this case, solitary rugose corals settled as larvae on crinoid stems, perhaps at a spot where the epidermis was missing for some reason (injury, disease). Both the crinoid and the coral began to grow around each other. By doing so, the affected crinoid columnals formed a swelling, where ultimately only an opening slightly larger than the coral orifice remained. We discuss both macroecological and small‐scale synecological aspects of this biocoenosis. The coral profited from its elevated home because it reached into more rapid currents providing the polyp with more food than at the densely populated seafloor, which was probably covered by a coral‐meadow around the mounds and hydrothermal vents. □Corals, crinoids, Early Devonian, epizoans, Morocco, Rugosa. 相似文献
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Annemarie MM Vlaar Marinus JPG van Kroonenburgh Alfons GH Kessels Wim EJ Weber 《BMC neurology》2007,7(1):27
Background
Parkinson's disease (PD) is the second most common neurodegenerative disorder. One of the most widely used techniques to diagnose PD is a Single Photon Emission Computer Tomography (SPECT) scan to visualise the integrity of the dopaminergic pathways in the brain. Despite this there remains some discussion on the value of SPECT in the differential diagnosis of PD. We did a meta-analysis of all the existing literature on the diagnostic accuracy of both pre- and post-synaptic SPECT imaging in the differential diagnosis of PD. 相似文献9.
Catherine E. Jessop Timothy J. Tavender Rachel H. Watkins Joseph E. Chambers Neil J. Bulleid 《The Journal of biological chemistry》2009,284(4):2194-2202
The formation of disulfides within proteins entering the secretory pathway
is catalyzed by the protein disulfide isomerase family of endoplasmic
reticulum localized oxidoreductases. One such enzyme, ERp57, is thought to
catalyze the isomerization of non-native disulfide bonds formed in
glycoproteins with unstructured disulfide-rich domains. Here we investigated
the mechanism underlying ERp57 specificity toward glycoprotein substrates and
the interdependence of ERp57 and the calnexin cycle for their correct folding.
Our results clearly show that ERp57 must be physically associated with the
calnexin cycle to catalyze isomerization reactions with most of its
substrates. In addition, some glycoproteins only require ERp57 for correct
disulfide formation if they enter the calnexin cycle. Hence, the specificity
of ER oxidoreductases is not only determined by the physical association of
enzyme and substrate but also by accessory factors, such as calnexin and
calreticulin in the case of ERp57. These conclusions suggest that the calnexin
cycle has evolved with a specialized oxidoreductase to facilitate native
disulfide formation in complex glycoproteins.The ability to form disulfide bonds within proteins entering the secretory
pathway is essential for cell survival and occurs within the endoplasmic
reticulum (ER).3 For
proteins with few disulfides, the process can be catalyzed by oxidation of
cysteine residues to form the correct, native disulfide; however, for proteins
with several disulfides, an isomerization reaction is also required to correct
non-native disulfides formed following oxidation
(1). Both these reactions are
catalyzed by a group of ER-resident proteins that belong to the protein
disulfide isomerase (PDI) family, which comprises over 17 members
(2). It is well established
that PDI and several other family members are able to catalyze the formation
and isomerization of disulfides in vitro, although the exact function
of each of the family members in vivo is unknown. It is still an open
question as to whether they all catalyze similar reactions and have distinct
substrate specificities or whether they have distinct enzymatic functions
related to the breaking and formation of disulfides.For one member of the PDI family, the function and substrate specificity is
a little clearer. ERp57 has been shown previously to interact specifically
with glycoproteins during their folding
(3). The enzyme is physically
associated with either calnexin or calreticulin
(4) and is therefore ideally
placed to catalyze correct disulfide formation within proteins entering the
calnexin/calreticulin cycle (referred to subsequently just as the calnexin
cycle). In addition, the ability of ERp57 to catalyze the refolding of
substrates in vitro is greatly enhanced if the substrate is bound to
calnexin (5). Recently,
substrates for the reduction or isomerization reaction catalyzed by ERp57 have
been identified by trapping mixed disulfides between enzyme and substrate
(6). Strikingly, there was an
overrepresentation of substrate proteins with cysteine-rich domains containing
little secondary structure, suggesting that the main function of ERp57 is in
the isomerization of non-native disulfides. ERp57 has also been shown to
function independently from the calnexin cycle. It is a component of the MHC
class I loading complex where it forms a disulfide-linked complex with tapasin
and is thought to either stabilize the complex or facilitate correct assembly
of class I molecules (7,
8). Recently, ERp57 has been
demonstrated to isomerize interchain disulfides in the major capsid protein,
VP1, of simian virus 40 (9).
The ability to dissociate VP1 pentamers by ERp57 does not require the
substrate to interact with the calnexin cycle. Hence, it is still unclear how
ERp57 recognizes its substrates, and in particular, whether this recognition
is solely determined by an interaction with the calnexin cycle.The recognition of substrates by PDI is somewhat clearer in that one
particular domain within the protein (the b′ domain) has been shown to
be primarily responsible for substrate recognition and peptide binding
(10). The corresponding domain
within ERp57 has been shown to be responsible for interaction with the
calnexin cycle (11),
suggesting that for ERp57, substrate recognition must occur outside this
domain or is determined solely by substrate interaction with calnexin via its
oligosaccharide side chain. Hence, the aim of our study was to evaluate the
necessity of the calnexin cycle both for ERp57 to recognize its substrates and
for correct folding of glycoproteins. ERp57 was found to be required for the
efficient folding of one substrate, influenza virus hemagglutinin (HA), but
only when it entered the calnexin cycle. HA did not require ERp57 to fold if
it was blocked from entering the calnexin cycle. In contrast, β1-integrin
does not fold efficiently either if ERp57 was depleted or if ERp57 is blocked
from entering the calnexin cycle
(6). Although ERp57 may be
dispensable for the folding of some glycoproteins, the interaction with
calnexin commits them to an ERp57-dependent fate. We also found that the
majority of ERp57 substrates need to enter the calnexin cycle to be acted upon
by the enzyme, demonstrating that substrate specificity is primarily dependent
upon substrate entry into the calnexin cycle. 相似文献
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Joseph E. Chambers Timothy J. Tavender Ojore B. V. Oka Stacey Warwood David Knight Neil J. Bulleid 《The Journal of biological chemistry》2010,285(38):29200-29207
Disulfide formation in newly synthesized proteins entering the mammalian endoplasmic reticulum is catalyzed by protein disulfide isomerase (PDI), which is itself thought to be directly oxidized by Ero1α. The activity of Ero1α is tightly regulated by the formation of noncatalytic disulfides, which need to be broken to activate the enzyme. Here, we have developed a novel PDI oxidation assay, which is able to simultaneously determine the redox status of the individual active sites of PDI. We have used this assay to confirm that when PDI is incubated with Ero1α, only one of the active sites of PDI becomes directly oxidized with a slow turnover rate. In contrast, a deregulated mutant of Ero1α was able to oxidize both PDI active sites at an equivalent rate to the wild type enzyme. When the active sites of PDI were mutated to decrease their reduction potential, both were now oxidized by wild type Ero1α with a 12-fold increase in activity. These results demonstrate that the specificity of Ero1α toward the active sites of PDI requires the presence of the regulatory disulfides. In addition, the rate of PDI oxidation is limited by the reduction potential of the PDI active site disulfide. The inability of Ero1α to oxidize PDI efficiently likely reflects the requirement for PDI to act as both an oxidase and an isomerase during the formation of native disulfides in proteins entering the secretory pathway. 相似文献