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91.
Periklis?Makrythanasis Michel?Guipponi Federico?A.?Santoni Maha?Zaki Mahmoud?Y.?Issa Muhammad?Ansar Hanan?HamamyEmail author Stylianos?E.?AntonarakisEmail author 《Human genomics》2016,10(1):26
Background
The recent availability of whole-exome sequencing has opened new possibilities for the evaluation of individuals with genetically undiagnosed intellectual disability.Results
We report two affected siblings, offspring of first-cousin parents, with intellectual disability, hypotonia, short stature, growth hormone deficiency, and delayed bone age. All members of the nuclear family were genotyped, and exome sequencing was performed in one of the affected individuals. We used an in-house algorithm (CATCH v1.1) that combines homozygosity mapping with exome sequencing results and provides a list of candidate variants. One identified novel homozygous missense variant in KALRN (NM_003947.4:c.3644C>A: p.(Thr1215Lys)) was predicted to be pathogenic by all pathogenicity prediction software used (SIFT, PolyPhen, Mutation Taster). KALRN encodes the protein kalirin, which is a GTP-exchange factor protein with a reported role in cytoskeletal remodeling and dendritic spine formation in neurons. It is known that mice with ablation of Kalrn exhibit age-dependent functional deficits and behavioral phenotypes.Conclusion
Exome sequencing provided initial evidence linking KALRN to monogenic intellectual disability in man, and we propose that KALRN is the causative gene for the autosomal recessive phenotype in this family.92.
Spectrofluorimetric determination of thioridazine and flupentixol in dosage forms; application to content uniformity test 下载免费PDF全文
A reliable, sensitive, cheap and non‐extractive spectrofluorimetric method has been developed and validated for determination of thioridazine and flupentixol based on ternary complex formation with eosin and lead(II) in the presence of methylcellulose as surfactant at pH 3.2. Under the optimum conditions, the quantitative quenching effect of investigated drugs on the native fluorescence of eosin has been investigated. The quenching of the eosin fluorescence was measured at 517 nm after excitation at 462 nm. The different experimental parameters affecting the development and stability of the reaction products were carefully studied and optimized, and the results were satisfactory. The calibration plots were constructed over the range of 0.5–3.0 µg mL?1. The developed method was successfully applied for determination of investigated drugs in commercial tablets without interference from common excipients. It was further applied for content uniformity testing of flupentixol in its tablets. Statistical comparisons of the results with those of the reference methods revealed excellent agreement and indicated no significant difference in accuracy and precision. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
93.
László?K?lesEmail author Erzsébet?Kató Adrienn?Hanuska Zoltán?S.?Zádori Mahmoud?Al-Khrasani Tibor?Zelles Patrizia?Rubini Peter?IllesEmail author 《Purinergic signalling》2016,12(1):1-24
Glutamate is the main excitatory neurotransmitter of the central nervous system (CNS), released both from neurons and glial cells. Acting via ionotropic (NMDA, AMPA, kainate) and metabotropic glutamate receptors, it is critically involved in essential regulatory functions. Disturbances of glutamatergic neurotransmission can be detected in cognitive and neurodegenerative disorders. This paper summarizes the present knowledge on the modulation of glutamate-mediated responses in the CNS. Emphasis will be put on NMDA receptor channels, which are essential executive and integrative elements of the glutamatergic system. This receptor is crucial for proper functioning of neuronal circuits; its hypofunction or overactivation can result in neuronal disturbances and neurotoxicity. Somewhat surprisingly, NMDA receptors are not widely targeted by pharmacotherapy in clinics; their robust activation or inhibition seems to be desirable only in exceptional cases. However, their fine-tuning might provide a promising manipulation to optimize the activity of the glutamatergic system and to restore proper CNS function. This orchestration utilizes several neuromodulators. Besides the classical ones such as dopamine, novel candidates emerged in the last two decades. The purinergic system is a promising possibility to optimize the activity of the glutamatergic system. It exerts not only direct and indirect influences on NMDA receptors but, by modulating glutamatergic transmission, also plays an important role in glia-neuron communication. These purinergic functions will be illustrated mostly by depicting the modulatory role of the purinergic system on glutamatergic transmission in the prefrontal cortex, a CNS area important for attention, memory and learning. 相似文献
94.
Ziad A Audat Mahmoud H. Hajyousef Mohammad D. Fawareh Khaldoon M. Alawneh Mohannad A. Odat Mohammad M. Barbarawi Ali A. Alomari Rami A. Jahmani Mohammad A. Khatatbeh Mohammed A. Assmairan 《Scoliosis》2016,11(1):47
Background
This was a prospective study to evaluate the effect of multilevel vertebral augmentation in addition to conventional therapy in multiple myeloma patients.Methods
We treated 27 patients, whom were recently diagnosed to have multiple myeloma by two ways of treatment. Thirteen patients (group I) were treated with conventional therapy and 14 patients (group II) with adding vertebroplasty and kyphoplasty. Patients were evaluated pre-treatment and at half, one, two and 3-years post-treatment by using Oswestry Disability Index (ODI), the Stanford Score (SS) and the Spinal Instability Neoplastic Score (SINS).Results
Mean values of ODI, SS and SINS were 31.9 (63.8%), 4.3 and 13.8 for group I and 33.2 (66.4%), 4.6 and 12.8 for group II before starting treatment. Group II showed improvement better than group I at all follow-up intervals with best results at first 6 months. P-values at the end of the study were ODI?=?0.047, SS?=?0.180 and SINS?=?0.002. Mortality rates were equal of both groups (four patients of each group).Conclusion
Adding vertebral augmentation to conventional therapy improves multiple myeloma patients’ quality of life, but didn’t affect the mortality rate.95.
96.
A persistent challenge in the treatment of non‐small cell lung cancer (NSCLC) with EGFR is the emergence of drug‐resistant caused by somatic mutations. The EGFR L858R/T790 M double mutant (EGFRDM) was found to be the most alarming variant. Despite the development of a wide range of inhibitors, none of them could inhibit EGFRDM effectively. Recently, 11h and 45a , have been found to be potent inhibitors against EGFRDM through two distinctive mechanisms, non‐covalent and covalent binding, respectively. However, the structural and dynamic implications of the two modes of inhibitions remain unexplored. Herein, two molecular dynamics simulation protocols, coupled with free‐energy calculations, were applied to gain insight into the atomistic nature of each binding mode. The comparative analysis confirmed that there is a significant difference in the binding free energy between 11h and 45a (ΔΔGbind=?21.17 kcal/mol). The main binding force that governs the binding of both inhibitors is vdW, with a higher contribution for 45a . Two residues ARG841 and THR854 were found to have curtailed role in the binding of 45a to EGFRDM by stabilizing its flexible alcohol chain. The 45a binding to EGFRDM induces structural rearrangement in the active site to allow easier accessibility of 45a to target residue CYS797. The findings of this work can substantially shed light on new strategies for developing novel classes of covalent and non‐covalent inhibitors with increased specificity and potency. 相似文献
97.
Alibrahim Ammar Al-Gharabally Dunia Mahmoud Huda Dittrich Maria 《Extremophiles : life under extreme conditions》2019,23(6):765-781
Extremophiles - Microbes can be found in hypersaline environments forming diverse populations with complex ecological interactions. Microbes in such environments were found to be involved in the... 相似文献
98.
Maryam Farshadi Behrooz Johari Elham Erfani Ezadyar Mazaher Gholipourmalekabadi Mahmoud Azami Hamid Madanchi Seyed Mohammad Amin Haramshahi Abazar Yari Ayoob Karimizade Reza Nekouian Ali Samadikuchaksaraei 《Cell biology international》2019,43(12):1379-1392
The mechanical property of bone tissue scaffolds is one of the most important aspects in bone tissue engineering that has remained problematic. In our previous study, we fabricated a three‐dimensional scaffold from nano‐hydroxyapatite/gelatin (nHA/Gel) and investigated its efficiency in promoting bone regeneration both in vitro and in vivo. In the present study, the effect of adding silicon carbide (SiC) on the mechanical and biological behaviors of the nHA/Gel/SiC and bone regeneration in vivo were determined. nHA and SiC were synthesized and characterized by the X‐ray diffraction pattern and transmission electron microscope image. Layer solvent casting, freeze drying, and lamination techniques were applied to prepare these scaffolds. Then, the biocompatibility and cell adhesion behavior of the synthesized nHA/Gel/SiC scaffolds were investigated. For in vivo studies, rats were categorized into three groups: blank defect, blank scaffold, and rat bone marrow mesenchymal stem cells (rBM‐MSCs)/scaffold. After 1, 4, and 12 weeks post‐injury, the rats were sacrificed and the calvaria were harvested. Sections with a thickness of 5 µm thickness were prepared and stained with hematoxylin–eosin and Masson's Trichrome, and immunohistochemistry was performed. Our results showed that SiC effectively increased the mechanical properties of the nHA/Gel/SiC scaffold. No significant differences were observed in biocompatibility, cell adhesion, and cytotoxicity of the nHA/Gel/SiC in comparison with the nHA/Gel nanocomposite. Based on histological and immunohistochemical studies, both osteogenesis and collagenization were significantly higher in the rBM‐MSCs/scaffold group, quantitatively and qualitatively. The present study strongly suggests the potential of SiC as an alternative strategy to improve the mechanical and biological properties of bone tissue engineering scaffolds, and shows that the pre‐seeded nHA/Gel/SiC scaffold with rBM‐MSCs improves osteogenesis in the engineered bone implant. 相似文献
99.
Tanhaeian Abbas Jaafari Mahmoud Reza Ahmadi Farajollah Shahriari Vakili‐Ghartavol Roghayyeh Sekhavati Mohammad Hadi 《Probiotics and antimicrobial proteins》2019,11(3):1034-1041
Probiotics and Antimicrobial Proteins - Nowadays, cancer remains a major cause of death affecting millions of people. Currently, the antimicrobial peptides (AMPs) as potent anticancer therapeutic... 相似文献
100.
Jian Li Zhanrui Leng Yueming Wu Yizhou Du Zhicong Dai Asim Biswas Xiaojun Zheng Guanlin Li Esawy Kasem Mahmoud Hui Jia Daolin Du 《Journal of Plant Ecology》2022,15(3):429
入侵植物与重金属胁迫的相互作用研究进展
全球变化改变了植物群落的分布格局,包括入侵植物,而人为污染可能降低本地植物对入侵植物的抗性。因此,本文总结了近几十年本地植物、入侵植物和植物-土壤生态系统中重金属生物地球化学行为的研究,以加深我们对入侵植物与环境胁迫因子相互作用的认识。我们的研究结合已有文献报道表明:(i)入侵物种对环境胁迫的影响具有异质性, (ii)影响的大小是多变的, (iii)即使在同一影响类型内,影响类型也具有多向性。然而,入侵植物暴露在重金属环境中表现出更强的自我保护机制,对重金属的生物可利用性和毒性有正向或负向的影响。另一方面,由于入侵植物普遍具有较高的耐受性,加之本地植物暴露于有毒重金属污染时具有“逃逸行为”,重金属胁迫环境更有利于植物的成功入侵。但是,对于入侵植物的重金属等元素组成是否与污染地区的本地植物不同,目前尚无共识。因此,在全球范围内对外来入侵植物与本土植物的植物体内、凋落物和土壤污染物含量进行定量比较是今后研究的一个重要方向。 相似文献