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301.
302.
β-galactosidase activity in fibroblasts and tissues from sheep with a lysosomal storage disease 总被引:3,自引:0,他引:3
Amelia J. Ahern-Rindell Robert D. Murnane David J. Prieur 《Biochemical genetics》1988,26(11-12):733-746
Tissues and fibroblasts of sheep affected with an inherited, neuronal lysosomal storage disease expressed a deficiency of beta-galactosidase activity. Cerebrum, kidney, lung, spinal cord, and spleen from affected sheep had less than 8% of the beta-galactosidase activity present in the respective tissues of normal sheep. No evidence for the presence of an endogenous inhibitor in affected sheep was detected by mixing studies. Liver of affected sheep expressed a deficiency of beta-galactosidase activity only in the presence of the beta-D-glycosidase inhibitors, glucono-delta-lactone and 2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine. In these studies, we demonstrated the existence of tissue-specific beta-galactosidases in sheep and showed that the affected sheep have a deficiency of the lysosomal beta-galactosidase. Our results suggest that the high residual beta-galactosidase activity in liver of affected sheep can be attributed to a nonlysosomal beta-galactosidase that has a neutral pH optimum and may be under temporal regulation. 相似文献
303.
New natural inactivating mutations of the follicle-stimulating hormone receptor: correlations between receptor function and phenotype. 总被引:18,自引:0,他引:18
P Touraine I Beau A Gougeon G Meduri A Desroches C Pichard M Detoeuf B Paniel M Prieur J R Zorn E Milgrom F Kuttenn M Misrahi 《Molecular endocrinology (Baltimore, Md.)》1999,13(11):1844-1854
Premature ovarian failure occurs in almost 1% of women under age 40. Molecular alterations of the FSH receptor (FSHR) have recently been described. A first homozygous mutation of the FSHR was identified in Finland. More recently, we described two new mutations of the FSHR in a woman presenting a partial FSH-resistance syndrome (patient 1). We now report new molecular alterations of the FSHR in another woman (patient 2) who presented at the age of 19 with primary amenorrhea contrasting with normal pubertal development. She had high plasma FSH, and numerous ovarian follicles up to 3 mm in size were evidenced by ultrasonography. Histological and immunohistochemical examination of ovarian biopsies revealed the presence of a normal follicular development up to the antral stage and disruption at further stages. DNA sequencing showed two heterozygous mutations: Asp224Val in the extracellular domain and Leu601Val in the third extracellular loop of FSHR. Cells transfected with expression vectors encoding the wild type or the mutated Leu601Val receptors bound hormone with similar affinity, whereas binding was barely detectable with the Asp224Val mutant. Confocal microscopy showed the latter to have an impaired targeting to the cell membrane. This was confirmed by its accumulation as a mannose-rich precursor. Adenylate cyclase stimulation by FSH of the Leu601Val mutant receptor showed a 12+/-3% residual activity, whereas in patient 1 a 24+/-4% residual activity was detected for the Arg573Cys mutant receptor. These results are in keeping with the fact that estradiol and inhibin B levels were higher in patient 1 and that stimulation with recombinant FSH did not increase follicular size, estradiol, or inhibin B levels in patient 2 in contrast to what was observed for patient 1. Thus, differences in the residual activity of mutated FSHR led to differences in the clinical, biological, and histological phenotypes of the patient. 相似文献
304.
Danyel GJ Jennen Addie LJ Vereijken Henk Bovenhuis Richard MPA Crooijmans Jan J van der Poel Martien AM Groenen 《遗传、选种与进化》2005,37(3):215-228
In this report we describe the analysis of an advanced intercross line (AIL) to confirm the quantitative trait locus (QTL) regions found for fatness traits in a previous study. QTL analysis was performed on chromosomes 1, 3, 4, 15, 18, and 27. The AIL was created by random intercrossing in each generation from generation 2 (G2) onwards until generation 9 (G9) was reached. QTL for abdominal fat weight (AFW) and/or percentage abdominal fat (AF%) on chromosomes 1, 3 and 27 were confirmed in the G9 population. In addition, evidence for QTL for body weight at the age of 5 (BW5) and 7 (BW7) weeks and for the percentage of intramuscular fat (IF%) were found on chromosomes 1, 3, 15, and 27. Significant evidence for QTL was detected on chromosome 1 for BW5 and BW7. Suggestive evidence was found on chromosome 1 for AFW, AF% and IF%, on chromosome 15 for BW5, and on chromosome 27 for AF% and IF%. Furthermore, evidence on the chromosome-wise level was found on chromosome 3 for AFW, AF%, and BW7 and on chromosome 27 for BW5. For chromosomes 4 and 18, test statistics did not exceed the significance threshold. 相似文献
305.
Barbara Schimmer Saskia Luttikholt Jeannine LA Hautvast Elisabeth AM Graat Piet Vellema Yvonne THP van Duynhoven 《BMC veterinary research》2011,7(1):1-14
Background
Highly pathogenic avian influenza (HPAI) viruses have had devastating effects on poultry industries worldwide, and there is concern about the potential for HPAI outbreaks in the poultry industry in Great Britain (GB). Critical to the potential for HPAI to spread between poultry premises are the connections made between farms by movements related to human activity. Movement records of catching teams and slaughterhouse vehicles were obtained from a large catching company, and these data were used in a simulation model of HPAI spread between farms serviced by the catching company, and surrounding (geographic) areas. The spread of HPAI through real-time movements was modelled, with the addition of spread via company personnel and local transmission.Results
The model predicted that although large outbreaks are rare, they may occur, with long distances between infected premises. Final outbreak size was most sensitive to the probability of spread via slaughterhouse-linked movements whereas the probability of onward spread beyond an index premises was most sensitive to the frequency of company personnel movements.Conclusions
Results obtained from this study show that, whilst there is the possibility that HPAI virus will jump from one cluster of farms to another, movements made by catching teams connected fewer poultry premises in an outbreak situation than slaughterhouses and company personnel. The potential connection of a large number of infected farms, however, highlights the importance of retaining up-to-date data on poultry premises so that control measures can be effectively prioritised in an outbreak situation. 相似文献306.
Baptiste Poujol Anne Prieur‐Vernat Jean Dubranna Romain Besseau Isabelle Blanc Paula Prez‐Lpez 《Journal of Industrial Ecology》2020,24(1):248-262
Renewable energy systems are essential in coming years to ensure an efficient energy supply while maintaining environmental protection. Despite having low environmental impacts during operation, other phases of the life cycle need to be accounted for. This study presents a geo‐located life cycle assessment of an emerging technology, namely, floating offshore wind farms. It is developed and applied to a pilot project in the Mediterranean Sea. The materials inventory is based on real data from suppliers and coupled to a parameterized model which exploits a geographic information system wind database to estimate electricity production. This multi‐criteria assessment identified the extraction and transformation of materials as the main contributor to environmental impacts such as climate change (70% of the total 22.3 g CO2 eq/kWh), water use (73% of 6.7 L/kWh), and air quality (76% of 25.2 mg PM2.5/kWh), mainly because of the floater's manufacture. The results corroborate the low environmental impact of this emerging technology compared to other energy sources. The electricity production estimates, based on geo‐located wind data, were found to be a critical component of the model that affects environmental performance. Sensitivity analyses highlighted the importance of the project's lifetime, which was the main parameter responsible for variations in the analyzed categories. Background uncertainties should be analyzed but may be reduced by focusing data collection on significant contributors. Geo‐located modeling proved to be an effective technique to account for geographical variability of renewable energy technologies and contribute to decision‐making processes leading to their development. 相似文献
307.
Jacques Prieur Stphanie Barbu Catherine Blois‐Heulin Alban Lemasson 《Biological reviews of the Cambridge Philosophical Society》2020,95(3):531-554
Investigating in depth the mechanisms underlying human and non‐human primate intentional communication systems (involving gestures, vocalisations, facial expressions and eye behaviours) can shed light on the evolutionary roots of language. Reports on non‐human primates, particularly great apes, suggest that gestural communication would have been a crucial prerequisite for the emergence of language, mainly based on the evidence of large communication repertoires and their associated multifaceted nature of intentionality that are key properties of language. Such research fuels important debates on the origins of gestures and language. We review here three non‐mutually exclusive processes that can explain mainly great apes' gestural acquisition and development: phylogenetic ritualisation, ontogenetic ritualisation, and learning via social negotiation. We hypothesise the following scenario for the evolutionary origins of gestures: gestures would have appeared gradually through evolution via signal ritualisation following the principle of derived activities, with the key involvement of emotional expression and processing. The increasing level of complexity of socioecological lifestyles and associated daily manipulative activities might then have enabled the acquisition and development of different interactional strategies throughout the life cycle. Many studies support a multimodal origin of language. However, we stress that the origins of language are not only multimodal, but more broadly multicausal. We propose a multicausal theory of language origins which better explains current findings. It postulates that primates' communicative signalling is a complex trait continually shaped by a cost–benefit trade‐off of signal production and processing of interactants in relation to four closely interlinked categories of evolutionary and life cycle factors: species, individual and context‐related characteristics as well as behaviour and its characteristics. We conclude by suggesting directions for future research to improve our understanding of the evolutionary roots of gestures and language. 相似文献
308.
Farida F Berkhof Nynke E Doornewaard-ten Hertog Steven M Uil Huib AM Kerstjens Jan WK van den Berg 《Respiratory research》2013,14(1):125
Background
Macrolides reduce exacerbations in patients with COPD. Their effects on health status has not been assessed as primary outcome and is less clear. This study assessed the effects of prophylactic azithromycin on cough-specific health status in COPD-patients with chronic productive cough.Methods
In this randomised controlled trial 84 patients met the eligibility criteria: age of ≥40 years, COPD GOLD stage ≥2 and chronic productive cough. The intervention-group (n = 42) received azithromycin 250 mg 3 times a week and the control-group (n = 42) received a placebo. Primary outcome was cough-specific health status at 12 weeks, measured with the Leicester Cough Questionnaire (LCQ). Secondary outcomes included generic and COPD-specific health status and exacerbations. Changes in adverse events and microbiology were monitored.Results
Mean age of participants was 68 ± 10 years and mean FEV1 was 1.36 ± 0.47 L. The improvement in LCQ total score at 12 weeks was significantly greater with azithromycin (difference 1.3 ± 0.5, 95% CI 0.3;2.3, p = 0.01) and met the minimal clinically important difference. Similar results were found for the domain scores, and COPD-specific and generic health status questionnaires. Other secondary endpoints were non-significant. No imbalances in adverse events were found.Conclusions
Prophylactic azithromycin improved cough-specific health status in COPD-patients with chronic productive cough to a clinically relevant degree.Trial registration
ClinicalTrials.gov NCT01071161相似文献309.
Koen JP Verhees Nicholas AM Pansters Hoeke A Baarsma Alexander HV Remels Astrid Haegens Chiel C de Theije Annemie MWJ Schols Reinoud Gosens Ramon CJ Langen 《Respiratory research》2013,14(1):117
Background
Chronic obstructive pulmonary disease (COPD) is accompanied by pulmonary inflammation and associated with extra-pulmonary manifestations, including skeletal muscle atrophy. Glycogen synthase kinase-3 (GSK-3) has been implicated in the regulation of muscle protein- and myonuclear turnover; two crucial processes that determine muscle mass. In the present study we investigated the effect of the selective GSK-3 inhibitor SB216763 on muscle mass in a guinea pig model of lipopolysaccharide (LPS)-induced pulmonary inflammation-associated muscle atrophy.Methods
Guinea pigs were pretreated with either intranasally instilled SB216763 or corresponding vehicle prior to each LPS/saline challenge twice weekly. Pulmonary inflammation was confirmed and indices of muscle mass were determined after 12 weeks. Additionally, cultured skeletal muscle cells were incubated with tumor necrosis factor α (TNF-α) or glucocorticoids (GCs) to model the systemic effects of pulmonary inflammation on myogenesis, in the presence or absence of GSK-3 inhibitors.Results
Repeated LPS instillation induced muscle atrophy based on muscle weight and muscle fiber cross sectional area. Intriguingly, GSK-3 inhibition using SB216763 prevented the LPS-induced muscle mass decreases and myofiber atrophy. Indices of protein turnover signaling were unaltered in guinea pig muscle. Interestingly, inhibition of myogenesis of cultured muscle cells by TNF-α or synthetic GCs was prevented by GSK-3 inhibitors.Conclusions
In a guinea pig model of LPS-induced pulmonary inflammation, GSK-3 inhibition prevents skeletal muscle atrophy without affecting pulmonary inflammation. Resistance to inflammation- or GC-induced impairment of myogenic differentiation, imposed by GSK-3 inhibition, suggests that sustained myogenesis may contribute to muscle mass maintenance despite persistent pulmonary inflammation. Collectively, these results warrant further exploration of GSK-3 as a potential novel drug target to prevent or reverse muscle wasting in COPD. 相似文献310.
A new simple, rapid and sensitive reversed‐phase liquid chromatographic method was developed and validated for the simultaneous determination of methocarbamol (MET) and aspirin (ASP) in their combined dosage form. The separation of these compounds was achieved within 6.0 min on a CLC Shim‐pack C8 column (250 × 4.6 mm, 5 µm particle size) using isocratic mobile phase consisting of acetonitrile and 0.02 M dihydrogenphosphate buffer (30:70, v/v) at pH = 5.0. The analysis was performed at a flow rate of 1.0 mL/min with fluorescence detection at 277/313 nm for MET and 298/410 nm for ASP using real‐time programming. The selectivity, linearity of calibration, accuracy, inter‐ and intra‐day precision and recovery were examined as parts of the method validation. The concentration–response relationship was linear over concentration ranges of 0.02‐0.20 and 0.02‐0.40 µg/mL for MET and ASP, respectively, with a limit of detection of 6 and 32 ng/mL for MET and ASP, respectively. The proposed method was successfully applied for the analysis of both MET and ASP in prepared tablets with average recoveries of 99.88 ± 0.65% for MET and 100.44 ± 0.78% for ASP. The results were favourably compared to those obtained by a reference method. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献