492 research outputs found
Three novel mutations in the ANK membrane protein cause craniometaphyseal dysplasia with variable conductive hearing loss
No full textCraniometaphyseal dysplasia (CMD) is a rare, sclerosing skeletal disorder caused by mutations in ANKH, which encodes a putative pyrophosphate transporting membrane protein. Six distinct ANKH mutations have been described to date. We report here on three novel mutations in simplex patients with CMD. The c.1015T>C (p.Cys339Arg) mutation found in Patient A was associated with congenital facial palsy, early-onset conductive hearing loss, and a generalized undermodeling of the long bones. The c.1172T>C (p.Leu391Pro) mutation in Patient B was associated with facial palsy, progressive conductive hearing loss, and generalized undermodeling of tubular bones. A milder phenotype without cranial nerve affection was observed in Patient C, associated with a c.1001T>G (p.Leu334Arg) mutation. All affected residues lie in evolutionarily conserved sequence blocks. These additional cases and the associated mutations contribute to an improved appreciation of the variability of this rare skeletal dysplasia. (c) 2010 Wiley-Liss, Inc
Embryonic expression of the human MID1 gene and its mutations in Opitz syndrome
No full textOpitz syndrome (G/BBB syndrome, MIM145410, and MIM300000) is a midline congenital malformation characterised by hypertelorism, hypospadias and oesophagolaryngotracheal defects leading to swallowing difficulties and hoarse voice. This condition is genetically heterogeneous with an X-linked recessive form mapped to Xp22.3 and at least one autosomal dominant form mapped to chromosome 22q11.2. Recently, mutations in MID1 have been identified in the X-linked form of the disease but the gene for the autosomal dominant form on 22q11 remains unknown.
Here we report on MID1 mutations screening in a series of 14 patients with Opitz syndrome and the MID1 expression pattern in human embryos using hybridisation in situ. Finally, we investigated the contribution of chromosome X-inactivation studies to identify the X-linked form of the disease.
Six MID1 mutations were identified in our series. All mutations were novel except the R495X mutation previously reported in three unrelated patients. We report heart and hindbrain expression of MID1 during early human development. Obligate carrier mothers showed a random pattern of X-inactivation.
Vermis hypoplasia or agenesis was frequently present (4/9) in patients with MID1 mutation. The heart and hindbrain expression of MID1 during early human development further supports the view that heart defects and vermis hypoplasia or agenesis are features to be included in the malformative spectrum of the syndrome. Finally, the study of X-inactivation pattern in women does not help discrimination between X-linked and autosomal forms of the disease
A new synthesis of l-sugar and the use of D-(-)-quinic acid for synthesis of trihydroxyazepanes via beckmann rearrangement
No full text碩士近年來，由於L-carbohydrate在醫學界的應用，引起了許多的注意，故有許多文獻報導。
我們設計了由D-mannono-1,4-lactone為起始物，經過5個合成步驟合成了L-allono-1,4-lactone，其重要的方法在於一步反應過程裡，連續進行了兩次反轉立體位向，使得D-mannono-1,4-lactone中的C-4及C-5的立體方位改變，而得到L-allono-1,4-lactone。
另外，由於azasugars在醫學上的應用，它們扮演著一個重要的角色，就是能夠抑制醣水解酵素。它們被認為能夠用來治療癌症、病毒感染及糖尿病等症狀，且具有潛力可發展成為新藥物。許多有關azasugar的文獻報導，其中以五圓環(pyrrolidine)、六圓環(piperidine)為最多，而七圓環的azepane最少。而所合成7圓環azepanes中，又以tetrahydroxyazepanes最多、trihydroxyazepanes次之、dihydroxy-azepanes為最少。
由D-(-)-quinic acid為起始物，利用Beckmann rearrangement反應得到具保護基之七圓環azasugar，進一步在去除保護基即可獲得trihydroxyazepane。Recently, L-carbohydrate have been widely used in drug development. We reported herein an efficient synthesis of L-allono-1,4-lactone from D-mannono-1,4
-lactone in five-step sequence. The key feature of the method involved a one pot "double inversion” procedure at stereocenter of C-4 and C-5 of D-mannono-1,4
-lactone to obtain the L-allono-1,4-lactone.
On the other hand, azasugars played an important role as glycosidase inhibitors. They were used in treatment of cancer, viral infection and diabetes, and have potential to make new drugs.
There are many reports to azasugars which they focused much attentation on the preparation of various five- and six-member azasugars namely polyhydroxy pyrrolidine and piperidine, respectively. However, only a few reports have appeared to the synthesis of seven-member azasugar-azepanes. Tetrahydroxy-azepanes appeared most in literatures among seven-member azasugars. Only few cases of trihydroxyazepanes and dihydroxyazepanes were described. Two trihydroxyazepanes were synthesized via Beckmann rearrangement from readily available D-(-)-quinic acid and reported in this article.中文摘要…………………………………….……………………………I
英文摘要………………………………...………………………………II
目錄……………………………………………………………………..III
圖表目錄…………………………………….…………………………..V
附圖目錄……………………………………………………………….VII
縮寫名稱………………………………………………………………...X
第壹章 前言
1-1 醣類的介紹………………………………………………...………..1
1-2 iminosugar的介紹……………………………………...……………2
1-3研究動機 ……………………………………………………...…….6
第貳章 結果與討論
2-1 L-allono-1,4-lactone的合成份………………………………..........15
2-2 Trihydroxyazepanes的合成部份………………………...…………20
結論…………………………………………………………..................28
第參章 實驗與儀器
3-1 實驗基本條件……………………………………………………...29
3-2 溶劑的乾燥……………………………………………………...…29
3-3 實驗儀器與測試方法…………………...………………………....30第肆章 實驗步驟…………..…………………….…………………….33
參考資料………………………………………………………………..51
附圖………………………………………………………………….….54
圖表目錄
圖1已證實有抑制Glycosidases的化合物結構……………………...…3
圖2 Tetrahydroxyazepanes對於酵素的抑制活性………………………4
圖3 Trihydroxyazepanes對於酵素的抑制活性…………………………5
圖4 L-ddC and L-5FddC的化學結構……………………..…………….6
圖5利用D-ribonolactone合成L-lyxose………………..……...………..7
圖6利用D-mannono-1,4-lactone合成L-ribose…………………………7
圖7 Kim利用D-mannono-1,4-lactone合成L-ribose……………………9
圖8 D-mannose合成L-sugar的流程圖……………..……..……….….10
圖9 D-(-)-quinic acid合成N-Tosyl-3,4-disubstituted
hexahydroazepanes………………………………...........................11
圖10 balanol的化學結構……………………………………………….11
圖11 D-(-)-quinic acid合成N-Tosyl-3,4-disubstituted
hexahydroazepanes的流程………………………………………12
圖12合成trihydroxyazepanes的流程………………………………….14
圖13化合物7的合成步驟…………………………..………………....17
圖14化合物5合成化合物7反應途徑..…………………………….....17
圖15合成4-Thio-L-lyxono-1,4-lactone的反應途徑………………..…18
圖16化合物7合成化合物8…………………………….…………...…19
圖17利用D-(-)-quinic acid合成化合物10…………...……………… 20
圖18化合物11的合成合驟……………………………………………21
圖19化合物14及15的合成步驟……………………..……………….22
圖20化合物16及17的合成步驟………………..…………………….23
圖21化合物12及13的反應途徑 …………………….………………24
圖22由化合物18合成化合物19及20…………….…………………..25
圖23化合物24的合成步驟……………………………………………26
圖24化合物16的合成步驟……………………………………………26
附圖目錄
附圖 1. 化合物1之1H NMR (300 MHz, CDCl3)……..………………54
附圖 2. 化合物1之13C NMR (75MHz, CDCl3)………..……………..55
附圖 3. 化合物2之1H NMR (300 MHz, CDCl3)………..……………56
附圖 4. 化合物2之13C NMR (75MHz, CDCl3)…………..…………..57
附圖 5. 化合物3之1H NMR (300 MHz, CDCl3)…………..…………58
附圖 6. 化合物3之13C NMR (75MHz, CDCl3)……………..………..59
附圖 7. 化合物4之1H NMR (300 MHz, CDCl3)……………..………60
附圖 8. 化合物4之13C NMR (75MHz, CDCl3)………..……………..61
附圖 9. 化合物5之1H NMR (300 MHz, CDCl3)………..……………62
附圖 10. 化合物5之13C NMR (75MHz, CDCl3)…..……..…………..63
附圖 11. 化合物7之1H NMR (300 MHz, CD3OD)…………………..64
附圖 12 化合物7之13C NMR (75MHz, CD3OD)……………………65
附圖 13. 化合物8之1H NMR (300 MHz, CD3OD)………….……….66
附圖 14. 化合物8之13C NMR (75MHz, CD3OD)………...………….67
附圖 15. 化合物8之NOESY圖譜 (500 MHz, CD3OD)…………….68
附圖 16. 化合物8之COSY圖譜 (500 MHz, CD3OD)……..………..69
附圖 17. 化合物10之1H NMR (300 MHz, CDCl3)……..……………70
附圖 18. 化合物10之13C NMR (75MHz, CDCl3)…………..………..71
附圖 19. 化合物11之1H NMR (300 MHz, CDCl3)…………..………72
附圖 20. 化合物11之13C NMR (75MHz, CDCl3)……………..……..73
附圖 21. 化合物12,13之1H NMR (300 MHz, CDCl3)……….………74
附圖 22. 化合物12,13之13C NMR (75MHz, CDCl3)…………….…..75
附圖 23. 化合物14之1H NMR (300 MHz, D2O)………...…….…….76
附圖 24. 化合物14之13C NMR (75MHz, D2O+CD3OD)….…..…….77
附圖 25. 化合物15之1H NMR (300 MHz, D2O)……...…….……….78
附圖 26 化合物15之13C NMR (75MHz, D2O+CD3OD)….….…..….79
附圖 27. 化合物16之1H NMR (300 MHz, D2O)…………………….80
附圖 28. 化合物16之13C NMR (75MHz, D2O+CD3OD)……………81
附圖 29. 化合物17之1H NMR (300 MHz,D2O)……………………..82
附圖 30. 化合物17之13C NMR (75MHz, D2O+CD3OD)……………83
附圖 31. 化合物19之1H NMR (300 MHz, CDCl3)……..……………84
附圖 32. 化合物19之13C NMR (75MHz, CDCl3)……………..……..85
附圖 33 化合物20之1H NMR (300 MHz, CDCl3)……..……….……86
附圖 34 化合物20之13C NMR (75MHz, CDCl3)………...…………..87
附圖 35. 化合物21之1H NMR (300 MHz, CDCl3)……..……………88
附圖 36. 化合物21之13C NMR (75MHz, CDCl3)…………..………..89
附圖 37. 化合物22之1H NMR (300 MHz, CDCl3)……..……………90
附圖 38. 化合物22之13C NMR (75MHz, CDCl3)……………..……..91
附圖 39 化合物24之1H NMR (300 MHz, CDCl3)……..…….………92
附圖 40 化合物24之13C NMR (75MHz, CDCl3)…………...………..93
附圖 41. 化合物26之1H NMR (300 MHz, CDCl3)……..……………94
附圖 42. 化合物26之13C NMR (75MHz, CDCl3)…………..………..95
附圖 43. 化合物17之NOESY圖譜 (600 MHz, D2O+CD3OD)….….96
附圖 44. 化合物17之COSY圖譜 (600 MHz, D2O+CD3OD).….…...97學號: 691170236, 學年度: 9
The molecular basis of X-linked spondyloepiphyseal dysplasia tarda
No full textThe X-linked form of spondyloepiphyseal dysplasia tarda (SEDL), a radiologically distinct skeletal dysplasia affecting the vertebrae and epiphyses, is caused by mutations in the SEDL gene. To characterize the molecular basis for SEDL, we have identified the spectrum of SEDL mutations in 30 of 36 unrelated cases of X-linked SEDL ascertained from different ethnic populations. Twenty-one different disease-associated mutations now have been identified throughout the SEDL gene. These include nonsense mutations in exons 4 and 5, missense mutations in exons 4 and 6, small (2-7 bp) and large (>1 kb) deletions, insertions, and putative splicing errors, with one splicing error due to a complex deletion/insertion mutation. Eight different frameshift mutations lead to a premature termination of translation and account for >43% (13/30) of SEDL cases, with half of these (7/13) being due to dinucleotide deletions. Altogether, deletions account for 57% (17/30) of all known SEDL mutations. Four recurrent mutations (IVS3+5G-->A, 157-158delAT, 191-192delTG, and 271-275delCAAGA) account for 43% (13/30) of confirmed SEDL cases. The results of haplotype analyses and the diverse ethnic origins of patients support recurrent mutations. Two patients with large deletions of SEDL exons were found, one with childhood onset of painful complications, the other relatively free of additional symptoms. However, we could not establish a clear genotype/phenotype correlation and therefore conclude that the complete unaltered SEDL-gene product is essential for normal bone growth. Molecular diagnosis can now be offered for presymptomatic testing of this disorder. Appropriate lifestyle decisions and, eventually, perhaps, specific SEDL therapies may ameliorate the prognosis of premature osteoarthritis and the need for hip arthroplasty.A.K. Gedeon, G.E. Tiller, M. Le Merrer, S. Heuertz, L. Tranebjaerg, D. Chitayat, S. Robertson, I.A. Glass, R. Savarirayan, W.G. Cole, D.L. Rimoin, B.G. Kousseff, H. Ohashi, B. Zabel, A. Munnich, J. Gecz and J.C. Mulle
Copper uptake kinetics in hydroponically-grown durum wheat (Triticum turgidum durum L.) as compared with soil's ability to supply copper
No full textThis study investigated (a) net Cu uptake kinetics in durum wheat (Triticum turgidum durum L.) exposed to free Cu2+ activities in solution ranging from 0.4 to 2,420 nM and (b) the relative importance of plant uptake and soil's ability to supply Cu2+ to the roots. Plant Cu flux showed a hyperbolic shape, enabling to estimate the Michaelis-Menten kinetic parameters (Fmax and KM) for durum wheat. Plant Cu flux was then compared with soil Cu flux as assessed by the Diffusive Gradient in Thin film technique on seven soil samples. This comparison suggested that the rate-limiting process of Cu bioavailability to durum wheat would be plant uptake kinetics in most contaminated soils with the exception of moderately contaminated, calcareous soils. However, theoretical considerations targeted soil's ability to supply Cu as the rate-limiting process in most soils for Cu (hyper-) accumulator plants with requirement larger than that of common crop species
P2NIA: Privacy-Preserving Non-Iterative Auditing
No full textInternational audienceUnlabelled - This study aimed to develop a practical, economically viable solution for treating hazardous landfill leachate using Pipe Freeze Crystallization (PFC) technology. The objective was to concentrate and solidify leachate from an effluent treatment plant processing approximately 8750 m annually, achieving resource recovery and environmental compliance. A 300 L h cooling demonstration plant was designed and implemented, incorporating a chiller, a secondary refrigerant mixture (40% ethylene glycol and 60% water), a clarifier, a reactor, and pumps. Μodelling with OLI software estimated recovery rates for salt and ice, providing a basis for operational adjustments. Leachate samples (2000 L) and concentrate (1000 L) were processed to evaluate the plant's performance in recovering clean water and NaSO. Experimental results confirmed the model predictions, with 302 L of concentrate yielding 102.9 kg of NaSO over 6 h and 273 L of leachate producing 118.7 kg of high-purity ice over 5.5 h. The energy consumption was measured at 171 kWh t of ice, aligning with theoretical predictions for a coefficient of performance of 1. These results validate the efficiency and feasibility of PFC in resource recovery. This study highlights the importance of PFC as a low-cost, energy-efficient technology for hazardous leachate treatment. Its scalability and ability to recover valuable resources such as NaSO and clean water present a sustainable alternative to conventional methods, contributing to zero-waste management goals in waste treatment practices. Supplementary information - The online version contains supplementary material available at 10.1007/s40710-025-00757-3
ChemInform Abstract: Enantiopure Hydroxylactones from L-Ascorbic and D-Isoascorbic Acids. Part 1. Synthesis of (-)-Muricatacin (VII).
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