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311.
Ortega Roldan JL Romero Romero ML Ora A Ab E Lopez Mayorga O Azuaga AI van Nuland NA 《Journal of biomolecular NMR》2007,39(4):331-336
CD2 associated protein (CD2AP) is an adaptor protein that plays an important role in cell to cell union needed for the kidney
function. CD2AP interacts, as an adaptor protein, with different natural targets, such as CD2, nefrin, c-Cbl and podocin.
These proteins are believed to interact to one of the three SH3 domains that are positioned in the N-terminal region of CD2AP.
To understand the network of interactions between the natural targets and the three SH3 domains (SH3-A, B and C), we have
started to determine the structures of the individual SH3 domains. Here we present the high-resolution structure of the SH3-C
domain derived from NMR data. Full backbone and side-chain assignments were obtained from triple-resonance spectra. The structure
was determined from distance restraints derived from high-resolution 600 and 800 MHz NOESY spectra, together with phi and psi torsion angle restraints based on the analysis of 1HN, 15N, 1Hα, 13Cα, 13CO and 13Cβ chemical shifts. Structures were calculated using CYANA and refined in water using RECOORD. The three-dimensional structure
of CD2AP SH3-C contains all the features that are typically found in other SH3 domains, including the general binding site
for the recognition of polyproline sequences. 相似文献
312.
Scola AM Higginbottom A Partridge LJ Reid RC Woodruff T Taylor SM Fairlie DP Monk PN 《The Journal of biological chemistry》2007,282(6):3664-3671
C5L2 is a new cellular receptor found to interact with the human anaphylatoxins complement factor C5a and its C-terminal cleavage product C5a des Arg. The classical human C5a receptor (C5aR) preferentially binds C5a, with a 10-100-fold lower affinity for C5a des Arg. In contrast, C5L2 binds both ligands with nearly equal affinity. C5aR presents acidic and tyrosine residues in its N terminus that interact with the core of C5a while a hydrophobic pocket formed by the transmembrane helices interacts with residues in the C terminus of C5a. Here, we have investigated the molecular basis for the increased affinity of C5L2 for C5a des Arg. Rat and mouse C5L2 preferentially bound C5a des Arg, whereas rodent C5aR showed much higher affinity for intact C5a. Effective peptidic and non-peptidic ligands for the transmembrane hydrophobic pocket of C5aR were poor inhibitors of ligand binding to C5L2. An antibody raised against the N terminus of human C5L2 did not affect the binding of C5a to C5L2 but did inhibit C5a des Arg binding. A chimeric C5L2, containing the N terminus of C5aR, had little effect on the affinity for C5a des Arg. Mutation of acidic and tyrosine residues in the N terminus of human C5L2 revealed that 3 residues were critical for C5a des Arg binding but had little involvement in C5a binding. C5L2 thus appears to bind C5a and C5a des Arg by different mechanisms, and, unlike C5aR, C5L2 uses critical residues in its N-terminal domain for binding only to C5a des Arg. 相似文献
313.
Mehner Thomas Rapp Tobias Monk Christopher T. Beck Mara E. Trudeau Ashley Kiljunen Mikko Hilt Sabine Arlinghaus Robert 《Ecosystems》2019,22(2):346-362
Ecosystems - It is well documented that aquatic ecosystems may be subsidized by naturally derived terrestrial carbon sources. In contrast, the intentional or unintentional subsidy of animal... 相似文献
314.
运用16种酶蛋白编码的23个遗传座位对突尼斯非洲跳鼠(Jaculus jaculus)和埃及跳鼠(J. orientalis)自然群体的遗传变异和分化进行了电泳分析。结果表明,与其他啮齿动物等哺乳动物的相关数据比较,发现这两个种群体的遗传变异水平较低。非洲跳鼠群体的观测杂合度 (Hobs) 为0.08—0.19,多态座位百分比(P)为26.2%—45.2%,每个座位的平均等位基因数(A)为1.1—1.4;埃及跳鼠的Hobs为0.10—0.15,P为29.3%—44.1%,A为1.1—1.7。两个种群体各自的遗传分化程度较低(非洲跳鼠和埃及跳鼠的Fst分别为0.0017和0.0019)。而两个种群体间的Fst为0.607(P<0.05),表明两个种之间高度的遗传分化。本研究支持这两个种分类地位的合法性,并强调了地理因素(环境类型和生物气候阶段)对两个种遗传结构的影响。 相似文献
315.
Stefan Vordenbäumen Leo AB Joosten Johannes Friemann Matthias Schneider Benedikt Ostendorf 《Arthritis research & therapy》2009,11(6):256-6
Synovial biopsies, gained either by blind needle biopsy or minimally invasive arthroscopy, offer additional information in
certain clinical situations where routine assessment has not permitted a certain diagnosis. In research settings, synovial
histology and modern applications of molecular biology increase our insight into pathogenesis and enable responses to treatment
with new therapeutic agents to be assessed directly at the pathophysiological level. This review focuses on the diagnostic
usefulness of synovial biopsies in the light of actual developments. 相似文献
316.
Alzheimer and prion diseases are neurodegenerative disorders characterised by the abnormal processing of amyloid-β (Aβ) peptide and prion protein (PrPC), respectively. Recent evidence indicates that PrPC may play a critical role in the pathogenesis of Alzheimer disease. PrPC interacts with and inhibits the β-secretase BACE1, the rate-limiting enzyme in the production of Aβ. More recently PrPC was identified as a receptor for Aβ oligomers and the expression of PrPC appears to be controlled by the amyloid intracellular domain (AICD). Here we review these observations and propose a feedback loop in the normal brain where PrPC exerts an inhibitory effect on BACE1 to decrease both Aβ and AICD production. In turn, the AICD upregulates PrPC expression, thus maintaining the inhibitory effect of PrPC on BACE1. In Alzheimer disease, this feedback loop is disrupted, and the increased level of Aβ oligomers bind to PrPC and prevent it from regulating BACE1 activity.Key words: alzheimer disease, amyloid-β, Aβ oligomers, amyloid intracellular domain, BACE1, presenilin, prion protein 相似文献
317.
318.
Wanessa LF Tavares Gleidice E Lavalle Mariana S Figueiredo Aline G Souza Angelica C Bertagnolli Fernando AB Viana Paulo RO Paes Rubens A Carneiro Guilherme AO Cavalcanti Marilia M Melo Geovanni D Cassali 《Acta veterinaria Scandinavica》2010,52(1):1-6
Background
Hypertension and proteinuria are medical complications associated with the multisystemic effects of long-term hypercortisolism in dogs with hyperadrenocorticism (HAC).Methods
This study investigated the relationships among adrenocorticotropic hormone (ACTH)-stimulation test results, systemic blood pressure, and microalbuminuria in clinically-healthy dogs (n = 100), in dogs affected with naturally occurring pituitary-dependent (PDH; n = 40), or adrenal-dependent hyperadrenocorticism (ADH; n = 30).Results
Mean systemic blood pressure was similar between clinically healthy dogs and dogs with HAC (p = 0.803). However the incidence of hypertension was highest in dogs with ADH (p = 0.017), followed by dogs with PDH, with the lowest levels in clinically healthy dogs (p = 0.019). Presence of microalbuminuria and albuminuria in clinically healthy dogs and dogs affected with HAC was significantly different (p < 0.001); incidences of albuminuria followed the same pattern of hypertension; highest incidence in dogs with ADH, and lowest level in clinically healthy dogs; but microalbuminuria showed a different pattern: clinically healthy dogs had highest incidences and dogs with ADH had lowest incidence. The presence of albuminuria was not associated with blood pressure values, regardless of whether dogs were clinically healthy or affected with ADH or PDH (p = 0.306).Conclusions
Higher incidence of hypertension and albuminuria, not microalbuminuria was seen in dogs affected with HAC compared to clinically healthy dogs; incidence of hypertension and albuminuria was significantly higher in dogs affected with ADH compared to PDH. However, presence of albuminuria was not correlated with systemic blood pressure. 相似文献319.
Construction of a large scale integrated map of macrophage pathogen recognition and effector systems
Sobia Raza Neil McDerment Paul A Lacaze Kevin Robertson Steven Watterson Ying Chen Michael Chisholm George Eleftheriadis Stephanie Monk Maire O'Sullivan Arran Turnbull Douglas Roy Athanasios Theocharidis Peter Ghazal Tom C Freeman 《BMC systems biology》2010,4(1):1-18
Background
Mathematical models provide abstract representations of the information gained from experimental observations on the structure and function of a particular biological system. Conferring a predictive character on a given mathematical formulation often relies on determining a number of non-measurable parameters that largely condition the model's response. These parameters can be identified by fitting the model to experimental data. However, this fit can only be accomplished when identifiability can be guaranteed.Results
We propose a novel iterative identification procedure for detecting and dealing with the lack of identifiability. The procedure involves the following steps: 1) performing a structural identifiability analysis to detect identifiable parameters; 2) globally ranking the parameters to assist in the selection of the most relevant parameters; 3) calibrating the model using global optimization methods; 4) conducting a practical identifiability analysis consisting of two (a priori and a posteriori) phases aimed at evaluating the quality of given experimental designs and of the parameter estimates, respectively and 5) optimal experimental design so as to compute the scheme of experiments that maximizes the quality and quantity of information for fitting the model.Conclusions
The presented procedure was used to iteratively identify a mathematical model that describes the NF-κB regulatory module involving several unknown parameters. We demonstrated the lack of identifiability of the model under typical experimental conditions and computed optimal dynamic experiments that largely improved identifiability properties. 相似文献320.
Wardley-Smith B.; Dore C.; Monk S.; Cohen S.; Eusden S.; Hawley D.; Halsey M. J. 《Journal of applied physiology》1987,62(3):978-982
Pregnant T-O mice were exposed to 50 ATA He-O2 pressure for 4 days at different stages of gestation: 4-7, 6-9, and 9-12 days gestation. Controls were exposed to 1 atmosphere absolute (ATA) air. After the exposure period, pregnancy continued until 18 days gestation when the mice were killed and autopsied. Data were collected relating to the litters and placentas (Litter size, percent resorptions, placental weight, fetal-to-placental ratio) and fetuses (weight, crown-rump length, sex, skeletal abnormalities) and analyzed using analysis of variance. Results showed a small but significant increase in the percent resorptions in the pressure group and also a decrease in crown-rump length and placental weight. None of these changes were related to the stage of gestation in which the mice were exposed. No teratogenic effects of pressure were seen. We conclude that exposure to 50 ATA He-O2 during pregnancy in mice produces a small nonselective effect on fetal growth and development but does not affect any specific event taking place during these stages of embryogenesis. 相似文献