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51.
Raman Kumar Mark?A. Corbett Bregje?W.M. van?Bon Joshua?A. Woenig Lloyd Weir Evelyn Douglas Kathryn?L. Friend Alison Gardner Marie Shaw Lachlan?A. Jolly Chuan Tan Matthew?F. Hunter Anna Hackett Michael Field Elizabeth?E. Palmer Melanie Leffler Carolyn Rogers Jackie Boyle Melanie Bienek Corinna Jensen Griet Van?Buggenhout Hilde Van?Esch Katrin Hoffmann Martine Raynaud Huiying Zhao Robin Reed Hao Hu Stefan?A. Haas Eric Haan Vera?M. Kalscheuer Jozef Gecz 《American journal of human genetics》2015,97(2):302-310
Export of mRNA from the cell nucleus to the cytoplasm is essential for protein synthesis, a process vital to all living eukaryotic cells. mRNA export is highly conserved and ubiquitous. Mutations affecting mRNA and mRNA processing or export factors, which cause aberrant retention of mRNAs in the nucleus, are thus emerging as contributors to an important class of human genetic disorders. Here, we report that variants in THOC2, which encodes a subunit of the highly conserved TREX mRNA-export complex, cause syndromic intellectual disability (ID). Affected individuals presented with variable degrees of ID and commonly observed features included speech delay, elevated BMI, short stature, seizure disorders, gait disturbance, and tremors. X chromosome exome sequencing revealed four missense variants in THOC2 in four families, including family MRX12, first ascertained in 1971. We show that two variants lead to decreased stability of THOC2 and its TREX-complex partners in cells derived from the affected individuals. Protein structural modeling showed that the altered amino acids are located in the RNA-binding domains of two complex THOC2 structures, potentially representing two different intermediate RNA-binding states of THOC2 during RNA transport. Our results show that disturbance of the canonical molecular pathway of mRNA export is compatible with life but results in altered neuronal development with other comorbidities. 相似文献
52.
Leen J. M. Seys Fien M. Verhamme Lisa L. Dupont Elke Desauter Julia Duerr Ayca Seyhan Agircan Griet Conickx Guy F. Joos Guy G. Brusselle Marcus A. Mall Ken R. Bracke 《PloS one》2015,10(6)
Introduction
Airway surface dehydration, caused by an imbalance between secretion and absorption of ions and fluid across the epithelium and/or increased epithelial mucin secretion, impairs mucociliary clearance. Recent evidence suggests that this mechanism may be implicated in chronic obstructive pulmonary disease (COPD). However, the role of airway surface dehydration in the pathogenesis of cigarette smoke (CS)-induced COPD remains unknown.Objective
We aimed to investigate in vivo the effect of airway surface dehydration on several CS-induced hallmarks of COPD in mice with airway-specific overexpression of the β-subunit of the epithelial Na+ channel (βENaC).Methods
βENaC-Tg mice and wild-type (WT) littermates were exposed to air or CS for 4 or 8 weeks. Pathological hallmarks of COPD, including goblet cell metaplasia, mucin expression, pulmonary inflammation, lymphoid follicles, emphysema and airway wall remodelling were determined and lung function was measured.Results
Airway surface dehydration in βENaC-Tg mice aggravated CS-induced airway inflammation, mucin expression and destruction of alveolar walls and accelerated the formation of pulmonary lymphoid follicles. Moreover, lung function measurements demonstrated an increased compliance and total lung capacity and a lower resistance and hysteresis in βENaC-Tg mice, compared to WT mice. CS exposure further altered lung function measurements.Conclusions
We conclude that airway surface dehydration is a risk factor that aggravates CS-induced hallmarks of COPD. 相似文献53.
Annemieke Dhondt Ruben Pauwels Katrien Devreese Sunny Eloot Griet Glorieux Raymond Vanholder 《PloS one》2015,10(6)
Background and Objective
Low molecular weight heparins (LMWHs) are small enough to pass large pore dialysis membranes. Removal of LMWH if injected before the start of the session is possible during high-flux dialysis and hemodiafiltration. The aim of this study was to determine the optimal mode (place and time) of tinzaparin administration during postdilution hemodiafiltration.Study Design, Setting, Patients
In 13 chronic hemodiafiltration patients, 3 approaches of injection were compared in a randomised cross over trial: i) before the start of the session at the inlet blood line filled with rinsing solution (IN0), ii) 5 min after the start at the inlet line filled with blood (IN5) and iii) before the start of the session at the outlet blood line (OUT0). Anti-Xa activity, thrombin generation, visual clotting score and reduction ratios of urea and beta2microglobulin were measured.Results
Anti-Xa activity was lower with IN0 compared with IN5 and OUT0, and also more thrombin generation was observed with IN0. No differences were observed in visual clotting scores and no clinically relevant differences were observed in solute reduction ratio. An anti-Xa of 0.3 IU/mL was discriminative for thrombin generation. Anti-Xa levels below 0.3 IU/mL at the end of the session were associated with worse clotting scores and lower reduction ratio of urea and beta2microglobulin.Conclusions
Injection of tinzaparin at the inlet line before the start of postdilution hemodiafiltration is associated with loss of anticoagulant activity and can therefore not be recommended. Additionally, we found that an anti-Xa above 0.3 IU/mL at the end of the session is associated with less clotting and higher dialysis adequacy.Trial Registration
Clinicaltrials.gov NCT00756145 相似文献54.
Kriel J Haesendonckx S Rubio-Texeira M Van Zeebroeck G Thevelein JM 《BioEssays : news and reviews in molecular, cellular and developmental biology》2011,33(11):870-879
When cells are starved of their substrate, many nutrient transporters are induced. These undergo rapid endocytosis and redirection of their intracellular trafficking when their substrate becomes available again. The discovery that some of these transporters also act as receptors, or transceptors, suggests that at least part of the sophisticated controls governing the trafficking of these proteins has to do with their signaling function rather than with control of transport. In yeast, the general amino acid permease Gap1 mediates signaling to the protein kinase A pathway. Its endocytic internalization and intracellular trafficking are subject to amino acid control. Other nutrient transceptors controlling this signal transduction pathway appear to be subject to similar trafficking regulation. Transporters with complex regulatory control have also been suggested to function as transceptors in other organisms. Hence, precise regulation of intracellular trafficking in nutrient transporters may be related to the need for tight control of nutrient-induced signaling. 相似文献
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56.
The roots of a new green revolution 总被引:2,自引:0,他引:2
Griet Den Herder Gert Van Isterdael Tom Beeckman Ive De Smet 《Trends in plant science》2010,15(11):600-607
57.
Katrien de Groote Griet Velghe Hedwig K. Stals Myriam I. Baes Peter E. Declercq 《Cell biochemistry and function》1996,14(4):277-281
After incubating isolated rat hepatocytes with [1-14C]palmitic acid, CoA and ATP (+MgCl2), a significant amount of [1-14C]palmitoyl-CoA was found in the incubation medium. There was no correlation between its rate of synthesis and the degree of intactness of the cells. The results indicate that there is a long-chain fatty acyl-CoA synthetase active on the external surface of the hepatocyte plasma membrane. The activity of this enzyme was negligible in primary cultures of rat hepatocytes, suggesting that the exofacial long-chain acyl-CoA synthetase is an artifact of the collagenase perfusion technique used to prepare the hepatocytes. 相似文献
58.
In the symbiotic interaction with rhizobia, legumes develop nodules in which nitrogen fixation takes place. Upon submersion, most temperate legumes are incapable of nodulation, but tropical legumes that grow in waterlogged soils have acquired water stress tolerance for growth and nodulation. One well-studied model plant, the tropical, semi-aquatic Sesbania rostrata, develops stem-located adventitious root primordia that grow out into adventitious roots upon submergence and develop into stem nodules after inoculation with the microsymbiont, Azorhizobium caulinodans. Sesbania rostrata also has a nodulated underground root system. On well-aerated roots, nodules form via root hair curling infection in the zone, just above the root tip, where root hairs develop; on hydroponic roots, an alternative process is used, recruiting a cortical intercellular invasion program at the lateral root bases that skips the epidermal responses. This intercellular cortical invasion entails infection pocket formation, a process that involves cell death features and reactive oxygen species. The plant hormones ethylene and gibberellin are the major signals that act downstream from the bacterial nodulation factors in the nodulation and invasion program. Both hormones block root hair curling infection, but cooperate to stimulate lateral root base invasion and play a role in infection thread formation, meristem establishment, and differentiation of meristem descendants. 相似文献
59.
Jose Antonio Pedroza-Garcia Thomas Eekhout Ignacio Achon Maher-Un Nisa Griet Coussens Ilse Vercauteren Hilde Van den Daele Laurens Pauwels Mieke Van Lijsebettens Ccile Raynaud Lieven De Veylder 《The Plant cell》2021,33(8):2662
The ataxia-telangiectasia mutated (ATM) and ATM and Rad3-related (ATR) kinases coordinate the DNA damage response. The roles described for Arabidopsis thaliana ATR and ATM are assumed to be conserved over other plant species, but molecular evidence is scarce. Here, we demonstrate that the functions of ATR and ATM are only partially conserved between Arabidopsis and maize (Zea mays). In both species, ATR and ATM play a key role in DNA repair and cell cycle checkpoint activation, but whereas Arabidopsis plants do not suffer from the absence of ATR under control growth conditions, maize mutant plants accumulate replication defects, likely due to their large genome size. Moreover, contrarily to Arabidopsis, maize ATM deficiency does not trigger meiotic defects, whereas the ATR kinase appears to be crucial for the maternal fertility. Strikingly, ATR is required to repress premature endocycle onset and cell death in the maize endosperm. Its absence results in a reduction of kernel size, protein and starch content, and a stochastic death of kernels, a process being counteracted by ATM. Additionally, while Arabidopsis atr atm double mutants are viable, no such mutants could be obtained for maize. Therefore, our data highlight that the mechanisms maintaining genome integrity may be more important for vegetative and reproductive development than previously anticipated.Differently from Arabidopsis, ATR activity in maize plays an essential role under control growth conditions, ensuring genome stability during kernel Development. 相似文献
60.
Sunny Eloot Wim Van Biesen Griet Glorieux Nathalie Neirynck Annemieke Dhondt Raymond Vanholder 《PloS one》2013,8(11)
Hemodialysis aims at removing uremic toxins thus decreasing their concentrations. The present study investigated whether Kt/Vurea, used as marker of dialysis adequacy, is correlated with these concentrations. Predialysis blood samples were taken before a midweek session in 71 chronic HD patients. Samples were analyzed by colorimetry, HPLC, or ELISA for a broad range of uremic solutes. Solute concentrations were divided into four groups according to quartiles of Kt/Vurea, and also of different other parameters with potential impact, such as age, body weight (BW), Protein equivalent of Nitrogen Appearance (PNA), Residual Renal Function (RRF), and dialysis vintage. Dichotomic concentration comparisons were performed for gender and Diabetes Mellitus (DM). Analysis of Variance in quartiles of Kt/Vurea did not show significant differences for any of the solute concentrations. For PNA, however, concentrations showed significant differences for urea (P<0.001), uric acid (UA), p-cresylsulfate (PCS), and free PCS (all P<0.01), and for creatinine (Crea) and hippuric acid (HA) (both P<0.05). For RRF, concentrations varied for β2-microglobulin (P<0.001), HA, free HA, free indoxyl sulfate, and free indole acetic acid (all P<0.01), and for p-cresylglucuronide (PCG), 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF), free PCS, and free PCG (all P<0.05). Gender and body weight only showed differences for Crea and UA, while age, vintage, and diabetes mellitus only showed differences for one solute concentration (UA, UA, and free PCS, respectively). Multifactor analyses indicated a predominant association of concentration with protein intake and residual renal function. In conclusion, predialysis concentrations of uremic toxins seem to be dependent on protein equivalent of nitrogen appearance and residual renal function, and not on dialysis adequacy as assessed by Kt/Vurea. Efforts to control intestinal load of uremic toxin precursors by dietary or other interventions, and preserving RRF seem important approaches to decrease uremic solute concentration and by extension their toxicity. 相似文献