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排序方式: 共有262条查询结果,搜索用时 15 毫秒
101.
Lettie E. Rawlins Hashem Almousa Shazia Khan Stephan C. Collins Miroslav P. Milev Joseph Leslie Djenann Saint-Dic Valeed Khan Ana Maria Hincapie Jacob O. Day Lucy McGavin Christine Rowley Gaurav V. Harlalka Valerie E. Vancollie Wasim Ahmad Christopher J. Lelliott Asma Gul Binnaz Yalcin Andrew H. Crosby Michael Sacher Emma L. Baple 《PLoS genetics》2022,18(3)
The highly evolutionarily conserved transport protein particle (TRAPP) complexes (TRAPP II and III) perform fundamental roles in subcellular trafficking pathways. Here we identified biallelic variants in TRAPPC10, a component of the TRAPP II complex, in individuals with a severe microcephalic neurodevelopmental disorder. Molecular studies revealed a weakened interaction between mutant TRAPPC10 and its putative adaptor protein TRAPPC2L. Studies of patient lymphoblastoid cells revealed an absence of TRAPPC10 alongside a concomitant absence of TRAPPC9, another key TRAPP II complex component associated with a clinically overlapping neurodevelopmental disorder. The TRAPPC9/10 reduction phenotype was recapitulated in TRAPPC10-/- knockout cells, which also displayed a membrane trafficking defect. Notably, both the reduction in TRAPPC9 levels and the trafficking defect in these cells could be rescued by wild type but not mutant TRAPPC10 gene constructs. Moreover, studies of Trappc10-/- knockout mice revealed neuroanatomical brain defects and microcephaly, paralleling findings seen in the human condition as well as in a Trappc9-/- mouse model. Together these studies confirm autosomal recessive TRAPPC10 variants as a cause of human disease and define TRAPP-mediated pathomolecular outcomes of importance to TRAPPC9 and TRAPPC10 mediated neurodevelopmental disorders in humans and mice. 相似文献
102.
Turkoglu S Maresca A Alper M Kockar F Işık S Sinan S Ozensoy O Arslan O Supuran CT 《Bioorganic & medicinal chemistry》2012,20(7):2208-2213
Site-directed mutagenesis has been used to change three amino acid residues involved in the binding of inhibitors (Asn67Ile; Gln92Val and Leu204Ser) within the active site of human carbonic anhydrase (CA, EC 4.2.1.1) II (hCA II). Residues 67, 92 and 204 were changed from hydrophobic to hydrophilic ones, and vice versa. The Asn67Ile and Leu204Ser mutants showed similar k(cat)/K(M) values compared to the wild type (wt) enzyme, whereas the Gln92Val mutant was around 30% less active as a catalyst for CO(2) hydration to bicarbonate compared to the wt protein. Affinity for sulfonamides/sulfamates was decreased in all three mutants compared to wt hCA II. The effect was stronger for the Asn67Ile mutant (the closest residue to the zinc ion), followed by the Gln92Val mutant (residue situated in the middle of the active site) and weakest for the Leu204Ser mutant, an amino acid situated far away from the catalytic metal ion, at the entrance of the cavity. This study shows that small perturbations within the active site architecture have influences on the catalytic efficiency but dramatically change affinity for inhibitors among the CA enzymes, especially when the mutated amino acid residues are nearby the catalytic metal ion. 相似文献
103.
Anaerobic treatment of a chemical synthesis-based pharmaceutical wastewater in a hybrid upflow anaerobic sludge blanket reactor 总被引:2,自引:0,他引:2
In this study, performance of a lab-scale hybrid up-flow anaerobic sludge blanket (UASB) reactor, treating a chemical synthesis-based pharmaceutical wastewater, was evaluated under different operating conditions. This study consisted of two experimental stages: first, acclimation to the pharmaceutical wastewater and second, determination of maximum loading capacity of the hybrid UASB reactor. Initially, the carbon source in the reactor feed came entirely from glucose, applied at an organic loading rate (OLR) 1 kg COD/m(3) d. The OLR was gradually step increased to 3 kg COD/m(3) d at which point the feed to the hybrid UASB reactor was progressively modified by introducing the pharmaceutical wastewater in blends with glucose, so that the wastewater contributed approximately 10%, 30%, 70%, and ultimately, 100% of the carbon (COD) to be treated. At the acclimation OLR of 3 kg COD/m(3) d the hydraulic retention time (HRT) was 2 days. During this period of feed modification, the COD removal efficiencies of the anaerobic reactor were 99%, 96%, 91% and 85%, and specific methanogenic activities (SMA) were measured as 240, 230, 205 and 231 ml CH(4)/g TVS d, respectively. Following the acclimation period, the hybrid UASB reactor was fed with 100% (w/v) pharmaceutical wastewater up to an OLR of 9 kg COD/m(3) d in order to determine the maximum loading capacity achievable before reactor failure. At this OLR, the COD removal efficiency was 28%, and the SMA was measured as 170 ml CH(4)/g TVS d. The hybrid UASB reactor was found to be far more effective at an OLR of 8 kg COD/m(3) d with a COD removal efficiency of 72%. At this point, SMA value was 200 ml CH(4)/g TVS d. It was concluded that the hybrid UASB reactor could be a suitable alternative for the treatment of chemical synthesis-based pharmaceutical wastewater. 相似文献
104.
Complexity reduction of polymorphic sequences (CRoPS): a novel approach for large-scale polymorphism discovery in complex genomes 总被引:2,自引:0,他引:2
van Orsouw NJ Hogers RC Janssen A Yalcin F Snoeijers S Verstege E Schneiders H van der Poel H van Oeveren J Verstegen H van Eijk MJ 《PloS one》2007,2(11):e1172
Application of single nucleotide polymorphisms (SNPs) is revolutionizing human bio-medical research. However, discovery of polymorphisms in low polymorphic species is still a challenging and costly endeavor, despite widespread availability of Sanger sequencing technology. We present CRoPS as a novel approach for polymorphism discovery by combining the power of reproducible genome complexity reduction of AFLP with Genome Sequencer (GS) 20/GS FLX next-generation sequencing technology. With CRoPS, hundreds-of-thousands of sequence reads derived from complexity-reduced genome sequences of two or more samples are processed and mined for SNPs using a fully-automated bioinformatics pipeline. We show that over 75% of putative maize SNPs discovered using CRoPS are successfully converted to SNPWave assays, confirming them to be true SNPs derived from unique (single-copy) genome sequences. By using CRoPS, polymorphism discovery will become affordable in organisms with high levels of repetitive DNA in the genome and/or low levels of polymorphism in the (breeding) germplasm without the need for prior sequence information. 相似文献
105.
The peptide guanylin, first isolated from rat small intestine, is involved in the regulation of water–electrolyte transport between the intracellular and extracellular compartments of the epithelia. The main sites of guanylin expression are the intestinal, airway, or exocrine gland ductal epithelia where guanylin acts in a paracrine/luminocrine fashion. Because guanylin also circulates in the blood, sources of this peptide were sought in endocrine glands. Our group has already demonstrated the presence of guanylin-immunoreactive cells in the pars tuberalis of male rat adenohypophysis. In this study, we investigated whether guanylin-immunoreactive cells exist also in the adenohypophysial pars distalis and whether their appearance or distribution correlates with various physiological conditions in female rats or alters after gonadectomy in both sexes. These studies revealed that the rat pars distalis contains two guanylin-immunoreactive cell types, gonadotrophic cells, whose number varied notably during the estrous cycle, reached a peak in the proestrous phase, and increased consistently during pregnancy, in lactating animals, and after gonadectomy, and folliculo-stellate cells, a discrete number of which were found only in female rats at the estrous phase. These findings suggest that guanylin is involved in regulating gonadotrophic cell function. They also add important information on the controversially discussed functions of folliculo-stellate cells. 相似文献
106.
Ozensoy O Isik S Arslan O Arslan M Scozzafava A Supuran CT 《Journal of enzyme inhibition and medicinal chemistry》2005,20(4):383-387
The purification of red blood cell carbonic anhydrase (CA, EC 4.2.1.1) from ostrich (scCA) blood is reported, as well as an inhibition study of this enzyme with a series of aromatic and heterocylic sulfonamides. The ostrich enzyme showed a high activity, comparable to that of the human isozyme II, with kcat, of 1.2 x 10(6) s(-1) and kcat/KM of 1.8 x 10(7) M(-1)s(-1), and an inhibition profile quite different from that of the human red blood cell cytosolic isozymes hCA I and II. scCA has generally a lower affinity for sulfonamide inhibitors as compared to hCA I and II. The only sulfonamide which behaved as a very potent inhibitor of this enzyme was ethoxzolamide (KI = 3.9 nM) whereas acetazolamide and sulfanilamide behaved as weaker inhibitors (inhibition constants in the range 303-570 nM). Several other aromatic and heterocyclic sulfonamides, mostly derivatives of sulfanilamide, homosulfanilamide, 4-aminoethylbenzenesulfonamide or 5-amino-1,3,4-thiadiazole-2-sulfonamide, showed good affinities for the ostrich enzyme, with KI values in the range 25-72 nM. 相似文献
107.
Demirtas Y Ayhan S Tulmac M Findikcioglu F Ozkose Z Yalcin R Atabay K 《Plastic and reconstructive surgery》2005,115(2):620-626
The hemodynamic effects of perioperative stressors, including preoperative patient anxiety, intraoperative local anesthetic/adrenaline infiltrations, and some painful interventions, have not been fully elucidated in plastic surgery procedures. The present study was designed to determine the hemodynamic effects of perioperative stressor events in American Society of Anesthesiologists class I patients undergoing rhinoplasty procedures under general anesthesia. The study included 50 healthy patients, 18 to 51 years of age (mean age, 27 +/- 7 years), who underwent a rhinoplasty procedure in the authors' department. All patients were connected to a digital ambulatory Holter recorder for 24 hours starting on the day before the operation and continuing throughout the procedure. All of the patients received 10 ml of 2% lidocaine with 1:80,000 adrenaline 15 minutes after intubation. Observations consisted of heart rate, noninvasive blood pressure, and power spectral heart rate variability analyses, the latter of which is indicative of the sympathovagal balance of the patients. The majority of patients developed a persistent, moderate sinus tachycardia before the induction of anesthesia. After the infiltration of lidocaine/adrenaline, a mild to moderate and short-lasting tachycardia was detected. A similar increase in pulse rate was also noticed during lateral osteotomies. No significant blood pressure changes attributable to perioperative stressors (with the exclusion of general anesthesia induction, intubation, and extubation) were observed. Sympathetic activity was found to be responsible from marked tachycardia before the induction, which was attributable to preoperative anxiety. The authors' study has demonstrated that there are three hemodynamically unstable periods causing tachycardia for rhinoplasty patients that directly concern the plastic surgeon: immediate preoperative anxiety, local anesthetic/adrenaline injection, and lateral osteotomies. The authors conclude that these patients would benefit from routine use of premedications and that a lidocaine/adrenaline combination is a safe adjunct to general anesthesia in young rhinoplasty patients. In addition, a deeper anesthesia during local infiltration and osteotomies would be appropriate. 相似文献
108.
109.
Pinar A Yurdakul P Yildiz I Temiz-Arpaci O Acan NL Aki-Sener E Yalcin I 《Biochemical and biophysical research communications》2004,317(2):670-674
Our previously synthesized 37 compounds, which are 2,5,6-substituted benzoxazole, benzimidazole, benzothiazole, and oxazolo(4,5-b)pyridine derivatives, were tested for their eukaryotic DNA topoisomerase II inhibitory activity in cell free system and 28 were found to inhibit the topoisomerase II at an initial concentration of 100 microg/ml. After further testing at a lower range of concentrations, 12 derivatives, which were considered as positive topoisomerase inhibitors, exhibited IC50 values between 11.4 and 46.8 microM. Etoposide was used as the standard reference drug to compare the inhibitor activity. Among these compounds, 2-phenoxymethylbenzothiazole (3f), 6-nitro-2-(2-methoxyphenyl)benzoxazole (1a), 5-methylcarboxylate-2-phenylthiomethylbenzimidazole (3c), and 6-methyl-2-(2-nitrophenyl)benzoxazole (1c) were found to be more active than the reference drug etoposide. Present results point out that, besides the very well-known bi- and ter-benzimidazoles, compounds with single bicycle fused ring systems in their structure such as benzimidazole, benzoxazole, benzothiazole, and/or oxazolopyridine derivatives also exhibit significant topoisomerase II inhibitory activity. 相似文献
110.
Baskurt OK Yalcin O Ozdem S Armstrong JK Meiselman HJ 《American journal of physiology. Heart and circulatory physiology》2004,286(1):H222-H229
The effects of enhanced red blood cell (RBC) aggregation on nitric oxide (NO)-dependent vascular control mechanisms have been investigated in a rat exchange transfusion model. RBC aggregation for cells in native plasma was increased via a novel method using RBCs covalently coated with a 13-kDa poloxamer copolymer (Pluronic F-98); control experiments used RBCs coated with a nonaggregating 8.4-kDa poloxamer (Pluronic F-68). Rats exchange transfused with aggregating RBC suspensions demonstrated significantly enhanced RBC aggregation throughout the 5-day follow-up period, with mean arterial blood pressure increasing gradually over this period. Arterial segments ( approximately 300 microm in diameter) were isolated from gracilis muscle on the fifth day and mounted between two glass micropipettes in a special chamber equipped with pressure servo-control system. Dose-dependent dilation by ACh and flow-mediated dilation of arterial segments pressurized to 30 mmHg and preconstricted to 45-55% of the original diameter by phenylephrine were significantly blunted in rats with enhanced RBC aggregation. Both responses were totally abolished by nonspecific NO synthase (NOS) inhibitor (Nomega-nitro-l-arginine methyl ester) treatment of arterial segments, indicating that the responses were NO related. Additionally, expression of endothelial NOS protein was found to be decreased in muscle samples obtained from rats exchanged with aggregating cell suspensions. These results imply that enhanced RBC aggregation results in suppressed expression of NO synthesizing mechanisms, thereby leading to altered vasomotor tonus; the mechanisms involved most likely relate to decreased wall shear stresses due to decreased blood flow and/or increased axial accumulation of RBCs. 相似文献