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K. Kawabe K. Goto I. Nishino C. Angelini Y. K. Hayashi 《European journal of neurology》2004,11(10):657-661
Mutations in the dysferlin gene (DYSF) on chromosome 2p13 cause distinct phenotypes of muscular dystrophy: limb-girdle muscular dystrophy type 2B (LGMD2B), Miyoshi myopathy (MM), and distal anterior compartment myopathy, which are known by the term 'dysferlinopathy'. We performed mutation analyses of DYSF in 14 Italian patients from 10 unrelated families with a deficiency of dysferlin protein below 20% of the value in normal controls by immunoblotting analysis. We identified 11 different mutations, including eight missense and three deletion mutations. Nine of them were novel mutations. We also identified a unique 6-bp insertion polymorphism within the coding region of DYSF in 15% of Italian population, which was not observed in East Asian populations. The correlation between clinical phenotype and the gene mutations was unclear, which suggested the role of additional genetic and epigenetic factors in modifying clinical symptoms. 相似文献
3.
多发性骨髓瘤骨髓活检与形态学检查的比较(附31例分析) 总被引:1,自引:0,他引:1
目的 :探讨多发性骨髓瘤 (MM)骨髓涂片与活检联合应用在 MM诊断和治疗中的价值。方法 :31例 MM骨髓涂片采用瑞氏染色 ,骨髓活检采用塑料包埋法薄切片经 HGF染色。结果 :骨髓活检与骨髓涂片增生程度完全相符者占 48% ,活检高于形态者占 39% ,形态高于活检者占 13%。瘤细胞检出例数活检与形态完全相符者占 39% ,活检高于形态者占 48% ,形态高于活检者占 13%。结论 :骨髓涂片与活检结合可相互补充 ,对 MM诊断和治疗有十分重要的价值 相似文献
4.
目的阐述某些环状二苯基庚烷类化合物在1 H NMR谱中异常位移的原因。方法利用分子力场MM 2法计算环状二苯基庚烷类化合物的空间优势构象 ,分析MM 2法与X 射线单晶衍射法的异同 ,根据分析结果寻找某些环状二苯基庚烷类化合物在1 H NMR谱中异常位移的原因。结果阐明了某些环状二苯基庚烷类化合物在1 H NMR谱中异常位移的原因。结论采用MM2法计算alnusdiol的空间构象 ,其C1/C2 C1′/C2′与C1/C6 C1′/C6′的两面角的角度与X 射线单晶衍射的结果基本一致 ,提示用MM 2法计算二苯基庚烷类化合物的空间构象是可行的。在某些二苯醚型二苯基庚烷类化合物中 ,由于醚键的存在 ,使得该类化合物的两个苯环形成的两面角接近于 90° ,碳链上的某些氢可能处于一苯环的正屏蔽区 ,处于苯环正屏蔽区的氢将向高场位移 ,其位移幅度与该氢与苯环中心距离及该氢与苯环中心、苯环平面所形成的二面角有关 相似文献
5.
Richard A. E. Edden Nicolaas A. J. Puts Peter B. Barker 《Magnetic resonance in medicine》2012,68(3):657-661
Edited magnetic resonance spectroscopy makes possible noninvasive studies of the role of the inhibitory neurotransmitter GABA in the healthy brain and in disease processes. A major limitation of the methodology is coediting of macromolecular signals. Although it has previously been shown that macromolecular signal can be suppressed using a symmetrical editing scheme, this approach is rarely applied at field strength of 3T as insufficiently selective pulses result in loss of GABA signal (in addition to the intended suppression of macromolecular signal). In this article, the authors show that increasing the echo time to 80 ms lets more selective editing pulses be used, allowing for symmetric editing‐based suppression of coedited macromolecular signal without loss of GABA signal. The method is applied to acquire macromolecule‐suppressed GABA‐edited spectra in 10 healthy participants. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc. 相似文献
6.
Computational studies on horseshoe shape pocket of human orexin receptor type 2 and boat conformation of suvorexant by molecular dynamics simulations
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《Chemical biology & drug design》2018,92(1):1221-1231
The FDA approved drug suvorexant binds to the horseshoe shape pocket of OX2R with the boat conformation. The horseshoe shape pocket plays an important role on the biological activity of OX2R in the cell membrane. To study the binding mechanism between the horseshoe shape pocket of OX2R and boat conformation of suvorexant, the crystal structures of wild type and N324A mutant of OX2R in complex with antagonist suvorexant are chosen to perform molecular dynamics (MD) simulations, QM/MM, and MMGBSA calculations. By comparison with the wild type of OX2R, the results show the 1,2,3‐triazole and p‐toluamide groups of suvorexant are changed in the N324A mutant of OX2R during 200 ns MD simulations. The QM/MM and weak interaction analysis are employed to calculate the non‐covalent bonds interaction between suvorexant and key residues in the wild type and N324A mutant of OX2R. The MMGBSA calculations indicate the entropy energy is an important influence factor for suvorexant affinity in the distorted horseshoe shape pocket of OX2R. Our results not only show the horseshoe shape pocket of OX2R is the necessary conformation for the binding of antagonist suvorexant, but also give the important sites and structural features for antagonist design of OX2R. 相似文献
7.
The optimized geometries, interaction energies, dipole moments, and vibrational frequencies of guanine-hydrogen peroxide (GHP), cytosine-hydrogen peroxide (CHP), adenine-hydrogen peroxide (AHP), thymine-hydrogen peroxide (THP), guanine–cytosine-hydrogen peroxide (GC-(HP)n(n = 1–2)), and adenine–thymine-hydrogen peroxide (AT-(HP)n(n = 1–2)) complexes are investigated by ab initio methods and ABEEMσπ/MM fluctuating charge potential model. All geometries of guanine–cytosine-hydrogen peroxide (G–C-HP) and adenine–thymine-hydrogen peroxide (A–T-HP) complexes were obtained using B3LYP/6-311++G(d,p) method, and the energies were determined at the MP2/6-311++G(2d,2p) level with BSSE corrections. The ABEEMσπ/MM model gives reasonable geometries and interaction energies compared with the present ab initio methods. For G–C-HP and A–T-HP clusters, the linear coefficient of the interaction energies all reaches 0.998, and the average absolute deviation (AAD) are 0.95 and 1.42 kcal/mol, respectively, when compared with MP2/6-311++G(2d,2p)‖B3LYP/6-311++G(d,p) method. Moreover, the variations of hydrogen bond length of guanine–cytosine and adenine–thymine base pair affected by hydrogen peroxide molecules computed by ABEEMσπ/MM model are all obtained reasonable accordance with B3LYP results. The current study will avail to understanding the physiological relevance in DNA damage. 相似文献
8.
Serving as one of our primary environmental inputs, vision is the most sophisticated sensory system in humans. Here, we present recent findings derived from energetics, genetics and physiology that provide a more advanced understanding of color perception in mammals. Energetics of cis–trans isomerization of 11-cis-retinal accounts for color perception in the narrow region of the electromagnetic spectrum and how human eyes can absorb light in the near infrared (IR) range. Structural homology models of visual pigments reveal complex interactions of the protein moieties with the light sensitive chromophore 11-cis-retinal and that certain color blinding mutations impair secondary structural elements of these G protein-coupled receptors (GPCRs). Finally, we identify unsolved critical aspects of color tuning that require future investigation. 相似文献
9.
Cancer stem cells (CSCs) comprise a tumor subpopulation responsible for tumor maintenance, resistance to chemotherapy, recurrence and metastasis. The identification of this cell group is very important, but there is still no consensus on its characterization. Several CSC markers have been described, like CD133, CD24, CD44 and ALDH1, but more research to identify new markers to facilitate the identification of CSC in a heterogeneous tumoral mass is required. Thus, this article describes the CD26 expression as a CSC marker and the role that it plays in different types of cancer. CD26 expression correlates with some characteristics of CSCs, like the formation of spheres in vitro, formation of new tumors, and resistance to chemotherapy. CD26 is therefore suggested as an auxiliary marker for CSC in different types of cancer, and as a potential therapeutic target. 相似文献
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