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71.
Carlota Pascoal Sandra Brasil Rita Francisco Dorinda Marques-da-Silva Agnes Rafalko Jaak Jaeken Paula A. Videira Luísa Barros Vanessa dos Reis Ferreira 《Orphanet journal of rare diseases》2018,13(1):215
Background
Health-related Quality of Life (HrQoL) is a multidimensional measure, which has gained clinical and social relevance. Implementation of a patient-centred approach to both clinical research and care settings, has increased the recognition of patient and/or observer reported outcome measures (PROMs or ObsROMs) as informative and reliable tools for HrQoL assessment. Inherited Metabolic Diseases (IMDs) are a group of heterogeneous conditions with phenotypes ranging from mild to severe and mostly lacking effective therapies. Consequently, HrQoL evaluation is particularly relevant.Objectives
We aimed to: (1) identify patient and/or caregiver-reported HrQoL instruments used among IMDs; (2) identify the main results of the application of each HrQoL tool and (3) evaluate the main limitations of HrQoL instruments and study design/methodology in IMDs.Methods
A scoping review was conducted using methods outlined by Arksey and O’Malley. Additionally, we critically analysed each article to identify the HrQoL study drawbacks.Results
Of the 1954 studies identified, 131 addressed HrQoL of IMDs patients using PROMs and/or ObsROMs, both in observational or interventional studies. In total, we identified 32 HrQoL instruments destined to self- or proxy-completion; only 2% were disease-specific. Multiple tools (both generic and disease-specific) proved to be responsive to changes in HrQoL; the SF-36 and PedsQL questionnaires were the most frequently used in the adult and pediatric populations, respectively. Furthermore, proxy data often demonstrated to be a reliable approach complementing self-reported HrQoL scores. Nevertheless, numerous limitations were identified especially due to the rarity of these conditions.Conclusions
HrQoL is still not frequently assessed in IMDs. However, our results show successful examples of the use of patient-reported HrQoL instruments in this field. The importance of HrQoL measurement for clinical research and therapy development, incites to further research in HrQoL PROMs’ and ObsROMs’ creation and validation in IMDs.72.
M. Crispo A. P. Mulet L. Tesson N. Barrera F. Cuadro P. C. dos Santos-Neto T. H. Nguyen A. Crénéguy L. Brusselle I. Anegón A. Menchaca 《PloS one》2015,10(8)
While CRISPR/Cas9 technology has proven to be a valuable system to generate gene-targeted modified animals in several species, this tool has been scarcely reported in farm animals. Myostatin is encoded by MSTN gene involved in the inhibition of muscle differentiation and growth. We determined the efficiency of the CRISPR/Cas9 system to edit MSTN in sheep and generate knock-out (KO) animals with the aim to promote muscle development and body growth. We generated CRISPR/Cas9 mRNAs specific for ovine MSTN and microinjected them into the cytoplasm of ovine zygotes. When embryo development of CRISPR/Cas9 microinjected zygotes (n = 216) was compared with buffer injected embryos (n = 183) and non microinjected embryos (n = 173), cleavage rate was lower for both microinjected groups (P<0.05) and neither was affected by CRISPR/Cas9 content in the injected medium. Embryo development to blastocyst was not affected by microinjection and was similar among the experimental groups. From 20 embryos analyzed by Sanger sequencing, ten were mutant (heterozygous or mosaic; 50% efficiency). To obtain live MSTN KO lambs, 53 blastocysts produced after zygote CRISPR/Cas9 microinjection were transferred to 29 recipient females resulting in 65.5% (19/29) of pregnant ewes and 41.5% (22/53) of newborns. From 22 born lambs analyzed by T7EI and Sanger sequencing, ten showed indel mutations at MSTN gene. Eight showed mutations in both alleles and five of them were homozygous for indels generating out-of frame mutations that resulted in premature stop codons. Western blot analysis of homozygous KO founders confirmed the absence of myostatin, showing heavier body weight than wild type counterparts. In conclusion, our results demonstrate that CRISPR/Cas9 system was a very efficient tool to generate gene KO sheep. This technology is quick and easy to perform and less expensive than previous techniques, and can be applied to obtain genetically modified animal models of interest for biomedicine and livestock. 相似文献
73.
74.
Marques MP Girão T Pedroso De Lima MC Gameiro A Pereira E Garcia P 《Biochimica et biophysica acta》2002,1589(1):63-70
Cytotoxicity and cell growth inhibition studies were performed for three distinct polynuclear platinum(II) complexes of spermidine, which showed to have significant cytotoxic and antiproliferative properties on the HeLa cancer cell line. The chemical environment of the metal centres in the drugs, as well as the coordination pattern of the ligand, were found to be strongly determinant of their cytotoxic ability. In the light of the results gathered, the most effective anticancer compound among the ones tested (IC50=5 microM) was found to be the one displaying three difunctional (PtCl2N2) moieties ((PtCl2)3(spd)2). Both the cytotoxic activity and the antiproliferative properties of the complexes studied showed to be irreversible for all the concentrations tested. 相似文献
75.
Summary. Tryptophan is required in the pineal gland for the formation of serotonin, precursor of melatonin biosynthesis. The level
of this amino acid in the serum and in the pineal gland of the rat undergoes a circadian rhythm, and reduced plasma tryptophan
concentration decreases secretion of melatonin in humans. Tryptophan is transported into the cells by the long chain neutral
amine acid system T and by the aromatic amino acid system T. The high affinity component of [3H]tryptophan uptake was studied in pinealocytes of the rat. Inhibition was observed in the presence of phenylalanine or tyrosine,
but not in the presence of neutral amino acids, alanine, glycine, serine, lysine or by 2-aminobicyclo[2,2,1]-heptane-2-carboxylic
acid, a substrate specific for system L. The transport of tryptophan was temperature-dependent and trans-stimulated by phenylalanine and tyrosine, but was energy-, sodium-, chloride-, and pH-independent. In addition, the sulphydryl
agent N-ethylmaleimide did not modify the high affinity transport of tryptophan in pinealocytes. The kinetic parameters were not
significantly different at 12:00 as compared to 24:00 h. The treatment with the inhibitor of tryptophan hydroxylase, p-chlorophenylalanine, produced an increase in the maximal velocity of the uptake and a reduction in the affinity at 12:00,
but not at 24:00 h, probably indicating that during the day, the formation of serotonin in the pineal gland is favoured by
elevating the uptake of tryptophan, whereas at 24:00 h other mechanisms, such as induction of enzymes are taking place. High
affinity tryptophan uptake in the rat pineal gland occurs through system T and is upregulated during the day when the availability
of serotonin is reduced.
Received March 15, 2001 Accepted July 8, 2002 Published online January 20, 2003
Acknowledgements This work was supported by the Grant S1-3490 from Consejo Nacional de Investigaciones Cientificas y Tecnológicas (CONICIT),
Venezuela. We appreciate the secretarial assistance of Mrs. Isabel Otaegui. Carmen I. Gutiérrez is a PhD Student from Ciencias
Fisiológicas, Facultad de Medicina, Universidad Central de Venezueta (UCV), Caracas, and supported by Universidad Francisco
de Miranda, Coro, Falcón, Venezuela. Joseph Glykys is a Medical Student from Universidad de Carabobo, Valencia, Venezuela,
and an Assistant Student of Centro de Estudios Avanzados, IVIC.
Authors' address: Dr. Lucimey Lima, Laboratorio de Neuroquímica, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones
Científicas, Apdo. 21827, Caracas 1020-A, Venezuela, Fax: 58-212-504-1295, E-mail: llima@cbb.ivic.ve 相似文献
76.
Genome physical mapping from large-insert clones by fingerprint analysis with capillary electrophoresis: a robust physical map of Penicillium chrysogenum 总被引:2,自引:0,他引:2 下载免费PDF全文
Xu Z van den Berg MA Scheuring C Covaleda L Lu H Santos FA Uhm T Lee MK Wu C Liu S Zhang HB 《Nucleic acids research》2005,33(5):e50
Physical mapping with large-insert clones is becoming an active area of genomics research, and capillary electrophoresis (CE) promises to revolutionize the physical mapping technology. Here, we demonstrate the utility of the CE technology for genome physical mapping with large-insert clones by constructing a robust, binary bacterial artificial chromosome (BIBAC)-based physical map of Penicillium chrysogenum. We fingerprinted 23.1× coverage BIBAC clones with five restriction enzymes and the SNaPshot kit containing four fluorescent-ddNTPs using the CE technology, and explored various strategies to construct quality physical maps. It was shown that the fingerprints labeled with one or two colors, resulting in 40–70 bands per clone, were assembled into much better quality maps than those labeled with three or four colors. The selection of fingerprinting enzymes was crucial to quality map construction. From the dataset labeled with ddTTP–dROX, we assembled a physical map for P.chrysogenum, with 2–3 contigs per chromosome and anchored the map to its chromosomes. This map represents the first physical map constructed using the CE technology, thus providing not only a platform for genomic studies of the penicillin-producing species, but also strategies for efficient use of the CE technology for genome physical mapping of plants, animals and microbes. 相似文献
77.
78.
The termite Incisitermes schwarzi has multiple sex chromosomes that have arisen by repeated translocations between autosomes and previously existing sex chromosomes. Two sex-linked allozyme loci--Acp-1 and Est-3--are holozygous, not hemizygous, in males (the heterogametic sex). Both loci show less than 1% crossing-over between X and Y chromosomes, and alleles of both are in marked disequilibrium with respect to X vs Y linkage. The two loci assort independently in female meiosis, indicating that they lie on different sex chromosomes. But they are tightly linked in male meiosis because of nonrandom assortment of the multiple X and Y chromosomes in males of this species. The findings of holozygosity and strong linkage disequilibrium suggest that differential selection in the two sexes at or near these loci may be responsible for the establishment of the translocations in this species. The existence of active Y-linked alleles also suggests that the translocations may have occurred recently. 相似文献
79.
Pedro LG Santos PA da Silva JA Figueiredo AC Barroso JG Deans SG Looman A Scheffer JJ 《Phytochemistry》2001,57(2):245-250
The essential oils isolated from leaves of ten and from unripe berries of eight populations of Laurus azorica (Seub.) Franco, collected on five islands of the Azorean archipelago, were analysed by GC and GC-MS. All oil samples were dominated by their monoterpene fraction (60-94%), alpha-pinene (15-37%) and 1,8-cineole (12-31%) being the main components of the leaf oils, while trans-beta-ocimene (27-45%) and alpha-pinene (12-22%) were the main components of the oils from the berries. The sesquiterpene fractions of the oils ranged from 3 to 17% and the main components were beta-caryophyllene (traces-8%) and beta-elemene (traces-3%) both in the leaf and berry oils. Some phenylpropanoid components were also present, in total amounting to 17%, trans-cinnamyl acetate (215% of the leaf oils) being the main component of this fraction. Cluster analysis of the enantiomeric composition of alpha- and beta-pinene in the oils from the leaves clearly showed two groups, one constituted by the two populations growing on the island S. Jorge, and the other constituted by the remaining populations. 相似文献
80.
Sérgio M. Santos Sadaki Yokota Shrivallabh P. Kamat José A. S. Cavaleiro Tomonori Motokawa Tomomi Kato Mayu Mochizuki Toshiyuki Fujiwara Yuki Fujii Yoshitaka Tanaka 《Pigment cell & melanoma research》2014,27(3):376-386
Tyrosinase, a melanosomal membrane protein containing copper, is a key enzyme for melanin synthesis in melanocytes. Inulavosin inhibits melanogenesis by enhancing a degradation of tyrosinase in lysosomes. However, the mechanism by which inulavosin redirects tyrosinase to lysosomes is yet unknown. The analyses of structure–activity relationship of inulavosin and its benzo‐derivatives reveal that the hydroxyl and the methyl groups play a critical role in their inhibitory activity. Intriguingly, the docking studies to tyrosinase suggest that the compounds showing inhibitory activity bind through hydrophobic interactions to the cavity of tyrosinase below which the copper‐binding sites are located. This cavity is proposed to be required for the association with a chaperon that assists in copper loading to tyrosinase in Streptomyces antibioticus. Inulavosin and its benzo‐derivatives may compete with the copper chaperon and result in a lysosomal mistargeting of apo‐tyrosinase that has a conformational defect. 相似文献