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121.
PDZ domains are protein-protein interaction modules that are crucial for the assembly of structural and signalling complexes. They specifically bind to short C-terminal peptides and occasionally to internal sequences that structurally resemble such peptide termini. The binding of PDZ domains is dominated by the residues at the P(0) and P(-2) position within these C-terminal targets, but other residues are also important in determining specificity. In this study, we analysed the binding specificity of the third PDZ domain of protein tyrosine phosphatase BAS-like (PTP-BL) using a C-terminal combinatorial peptide phage library. Binding of PDZ3 to C-termini is preferentially governed by two cysteine residues at the P(-1) and P(-4) position and a valine residue at the P(0) position. Interestingly, we found that this binding is lost upon addition of the reducing agent dithiothrietol, indicating that the interaction is disulfide-bridge-dependent. Site-directed mutagenesis of the single cysteine residue in PDZ3 revealed that this bridge formation does not occur intermolecularly, between peptide and PDZ3 domain, but rather is intramolecular. These data point to a preference of PTP-BL PDZ3 for cyclic C-terminal targets, which may suggest a redox state-sensing role at the cell cortex. 相似文献
122.
Mutation of the mouse Rad17 gene leads to embryonic lethality and reveals a role in DNA damage-dependent recombination 下载免费PDF全文
Budzowska M Jaspers I Essers J de Waard H van Drunen E Hanada K Beverloo B Hendriks RW de Klein A Kanaar R Hoeijmakers JH Maas A 《The EMBO journal》2004,23(17):3548-3558
Genetic defects in DNA repair mechanisms and cell cycle checkpoint (CCC) genes result in increased genomic instability and cancer predisposition. Discovery of mammalian homologs of yeast CCC genes suggests conservation of checkpoint mechanisms between yeast and mammals. However, the role of many CCC genes in higher eukaryotes remains elusive. Here, we report that targeted deletion of an N-terminal part of mRad17, the mouse homolog of the Schizosaccharomyces pombe Rad17 checkpoint clamp-loader component, resulted in embryonic lethality during early/mid-gestation. In contrast to mouse embryos, embryonic stem (ES) cells, isolated from mRad17(5'Delta/5'Delta) embryos, produced truncated mRad17 and were viable. These cells displayed hypersensitivity to various DNA-damaging agents. Surprisingly, mRad17(5'Delta/5'Delta) ES cells were able to arrest cell cycle progression upon induction of DNA damage. However, they displayed impaired homologous recombination as evidenced by a strongly reduced gene targeting efficiency. In addition to a possible role in DNA damage-induced CCC, based on sequence homology, our results indicate that mRad17 has a function in DNA damage-dependent recombination that may be responsible for the sensitivity to DNA-damaging agents. 相似文献
123.
Roy L Bergeron JJ Lavoie C Hendriks R Gushue J Fazel A Pelletier A Morré DJ Subramaniam VN Hong W Paiement J 《Molecular biology of the cell》2000,11(8):2529-2542
Transitional endoplasmic reticulum (tER) consists of confluent rough and smooth endoplasmic reticulum (ER) domains. In a cell-free incubation system, low-density microsomes (1.17 g cc(-1)) isolated from rat liver homogenates reconstitute tER by Mg(2+)GTP- and Mg(2+)ATP-hydrolysis-dependent membrane fusion. The ATPases associated with different cellular activities protein p97 has been identified as the relevant ATPase. The ATP depletion by hexokinase or treatment with either N-ethylmaleimide or anti-p97 prevented assembly of the smooth ER domain of tER. High-salt washing of low-density microsomes inhibited assembly of the smooth ER domain of tER, whereas the readdition of purified p97 with associated p47 promoted reconstitution. The t-SNARE syntaxin 5 was observed within the smooth ER domain of tER, and antisyntaxin 5 abrogated formation of this same membrane compartment. Thus, p97 and syntaxin 5 regulate assembly of the smooth ER domain of tER and hence one of the earliest membrane differentiated components of the secretory pathway. 相似文献
124.
Tárrega C Ríos P Cejudo-Marín R Blanco-Aparicio C van den Berk L Schepens J Hendriks W Tabernero L Pulido R 《The Journal of biological chemistry》2005,280(45):37885-37894
The two regulatory residues that control the enzymatic activity of the mitogen-activated protein (MAP) kinase ERK2 are phosphorylated by the unique MAP kinase kinases MEK1/2 and dephosphorylated by several tyrosine-specific and dual specificity protein phosphatases. Selective docking interactions facilitate these phosphorylation and dephosphorylation events, controlling the specificity and duration of the MAP kinase activation-inactivation cycles. We have analyzed the contribution of specific residues of ERK2 in the physical and functional interaction with the ERK2 phosphatase inactivators PTP-SL and MKP-3 and with its activator MEK1. Single mutations in ERK2 that abrogated the dephosphorylation by endogenous tyrosine phosphatases from HEK293 cells still allowed efficient phosphorylation by endogenous MEK1/2. Discrete ERK2 mutations at the ERK2 docking groove differentially affected binding and inactivation by PTP-SL and MKP-3. Remarkably, the cytosolic retention of ERK2 by its activator MEK1 was not affected by any of the analyzed ERK2 single amino acid substitutions. A chimeric MEK1 protein, containing the kinase interaction motif of PTP-SL, bound tightly to ERK2 through its docking groove and behaved as a gain-of-function MAP kinase kinase that hyperactivated ERK2. Our results provide evidence that the ERK2 docking groove is more restrictive and selective for its tyrosine phosphatase inactivators than for MEK1/2 and indicate that distinct ERK2 residues modulate the docking interactions with activating and inactivating effectors. 相似文献
125.
Hendriks WH Harding DR Rutherfurd-Markwick KJ 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2004,139(2):245-251
The renal metabolism of the tripeptide, gamma-glutamylfelinylglycine, which our group recently identified in the blood of domestic cats (Felis catus), was investigated. To test our hypothesis that this unique tripeptide is metabolised by the kidney in a similar manner to glutathione-S-conjugates in other animal species, [(35)S]cysteine was administered intraperitoneally to an entire male cat, and urine collected at 1, 4 and 8 h post-injection. Radiolabelled fractions were isolated from the urine following reversed-phase (RP) HPLC. Four [(35)S]radiolabelled fractions were identified and characterised by amino acid analysis, mass spectrometry and comparison of retention times with synthetic compounds (felinine, N-acetyl felinine, felinylglycine, gamma-glutamylfelinylglycine). In addition to the previously described presence of free felinine, we showed the presence of several felinine-containing metabolites, including N-acetyl felinine, felinylglycine and unaltered gamma-glutamylfelinylglycine in cat urine. The results show that renal metabolism of gamma-glutamylfelinylglycine in cats, generally occurs in a similar manner to glutathione S-conjugates in other animal species, although the detection of felinylglycine indicates that subtle differences may exist. Additionally, our research indicates that previously reported estimates of felinine excretion in male cats need to be increased by as much as 54% to account for other felinine containing metabolites in the urine. 相似文献
126.
127.
Chromophore based analyses of steady‐state diffuse reflectance spectroscopy: current status and perspectives for clinical adoption 下载免费PDF全文
Torre M. Bydlon Rami Nachabé Nimmi Ramanujam Henricus J. C. M. Sterenborg Benno H. W. Hendriks 《Journal of biophotonics》2015,8(1-2):9-24
Diffuse reflectance spectroscopy is a rapidly growing technology in the biophotonics community where it has shown promise in its ability to classify different tissues. In the steady‐state domain a wide spectrum of clinical applications is supported with this technology ranging from diagnostic to guided interventions. Diffuse reflectance spectra provide a wealth of information about tissue composition; however, extracting biologically relevant information from the spectra in terms of chromophores may be more useful to gain acceptance into the clinical community. The chromophores that absorb light in the visible and near infrared wavelengths can provide information about tissue composition. The key characteristics of these chromophores and their relevance in different organs and clinical applications is the focus of this review, along with translating their use to the clinic.
128.
Sofie HM Manders Wietske Kievit Eddy Adang Herman L Brus Hein J Bernelot Moens Andre Hartkamp Lidy Hendriks Elisabeth Brouwer Henk Visser Harald E Vonkeman Jos Hendrikx Tim L Jansen Rene Westhovens Mart AFJ van de Laar Piet LCM van Riel 《Arthritis research & therapy》2015,17(1)
IntroductionFor patients with rheumatoid arthritis (RA) whose treatment with a tumour necrosis factor inhibitor (TNFi) is failing, several biological treatment options are available. Often, another TNFi or a biological with another mode of action is prescribed. The objective of this study was to compare the effectiveness and cost-effectiveness of three biologic treatments with different modes of action in patients with RA whose TNFi therapy is failing.MethodsWe conducted a pragmatic, 1-year randomised trial in a multicentre setting. Patients with active RA despite previous TNFi treatment were randomised to receive abatacept, rituximab or a different TNFi. The primary outcome (Disease Activity Score in 28 joints) and the secondary outcomes (Health Assessment Questionnaire Disability Index and 36-item Short Form Health Survey scores) were analysed using linear mixed models. Cost-effectiveness was analysed on the basis of incremental net monetary benefit, which was based on quality-adjusted life-years (calculated using EQ-5D scores), and all medication expenditures consumed in 1 year. All analyses were also corrected for possible confounders.ResultsOf 144 randomised patients, 5 were excluded and 139 started taking abatacept (43 patients), rituximab (46 patients) or a different TNFi (50 patients). There were no significant differences between the three groups with respect to multiple measures of RA outcomes. However, our analysis revealed that rituximab therapy is significantly more cost-effective than both abatacept and TNFi over a willingness-to-pay range of 0 to 80,000 euros.ConclusionsAll three treatment options were similarly effective; however, when costs were factored into the treatment decision, rituximab was the best option available to patients whose first TNFi treatment failed. However, generalization of these costs to other countries should be undertaken carefully.
Trial registration
Netherlands Trial Register number NTR1605. Registered 24 December 2008.Electronic supplementary material
The online version of this article (doi:10.1186/s13075-015-0630-5) contains supplementary material, which is available to authorized users. 相似文献129.
R. J. Achttien J. B. Staal S. van der Voort H. M. Kemps H. Koers M. W. A. Jongert E. J. M. Hendriks 《Netherlands heart journal》2015,23(1):6-17
Rationale
To improve the quality of exercise-based cardiac rehabilitation (CR) in patients with chronic heart failure (CHF) a practice guideline from the Dutch Royal Society for Physiotherapy (KNGF) has been developed.Guideline development
A systematic literature search was performed to formulate conclusions on the efficacy of exercise-based intervention during all CR phases in patients with CHF. Evidence was graded (1–4) according the Dutch evidence-based guideline development criteria.Clinical and research recommendations
Recommendations for exercise-based CR were formulated covering the following topics: mobilisation and treatment of pulmonary symptoms (if necessary) during the clinical phase, aerobic exercise, strength training (inspiratory muscle training and peripheral muscle training) and relaxation therapy during the outpatient CR phase, and adoption and monitoring training after outpatient CR.Applicability and implementation issues
This guideline provides the physiotherapist with an evidence-based instrument to assist in clinical decision-making regarding patients with CHF. The implementation of the guideline in clinical practice needs further evaluation.Conclusion
This guideline outlines best practice standards for physiotherapists concerning exercise-based CR in CHF patients. Research is needed on strategies to improve monitoring and follow-up of the maintenance of a physical active lifestyle after supervised CR. 相似文献130.
R. J. Achttien J. B. Staal S. van der Voort H. M. C. Kemps H. Koers M. W. A. Jongert E. J. M. Hendriks 《Netherlands heart journal》2013,21(10):429-438