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21.
Iqbal Aneela Khan Raham Sher Shehryar Kashmala Imran Anum Ali Faryal Attia Syeda Shah Shahen Mii Masahiro 《Plant Cell, Tissue and Organ Culture》2019,137(1):1-10
Plant Cell, Tissue and Organ Culture (PCTOC) - Four serotypes of the dengue virus that can cause severe disease in humans greatly increases the complexity of vaccine development. In this study, we... 相似文献
22.
Nicholas J. Ose Brandon M. Butler Avishek Kumar I. Can Kazan Maxwell Sanderford Sudhir Kumar S. Banu Ozkan 《PLoS computational biology》2022,18(4)
Many pathogenic missense mutations are found in protein positions that are neither well-conserved nor fall in any known functional domains. Consequently, we lack any mechanistic underpinning of dysfunction caused by such mutations. We explored the disruption of allosteric dynamic coupling between these positions and the known functional sites as a possible mechanism for pathogenesis. In this study, we present an analysis of 591 pathogenic missense variants in 144 human enzymes that suggests that allosteric dynamic coupling of mutated positions with known active sites is a plausible biophysical mechanism and evidence of their functional importance. We illustrate this mechanism in a case study of β-Glucocerebrosidase (GCase) in which a vast majority of 94 sites harboring Gaucher disease-associated missense variants are located some distance away from the active site. An analysis of the conformational dynamics of GCase suggests that mutations on these distal sites cause changes in the flexibility of active site residues despite their distance, indicating a dynamic communication network throughout the protein. The disruption of the long-distance dynamic coupling caused by missense mutations may provide a plausible general mechanistic explanation for biological dysfunction and disease. 相似文献
23.
Banu Y Matsuda M Yoshihara M Kondo M Sutou S Matsukuma S 《Molecular reproduction and development》2002,61(3):288-301
In a transgenic mouse, Golga3/Mea2 gene (human homolog: GOLGA3/golgin-160) was disrupted by a translocation at the site of the transgene integration. Exons 8-24 of the disrupted gene remained intact and formed a fusion gene (DeltaMea2) with the antisense strand of E. coli-derived transgene by means of a cryptic splice signal in there. The protein product of DeltaMea2, virtually a form truncated to 2/3 of the normal size, localized to Golgi apparatus of pachytene spermatocytes and round spermatids. DeltaMea2 expression was specific to the testis, but varied among separate seminiferous tubules. It also showed variation among homozygous individuals from 0.5 to 4.3% of the wild type (wt) level. At the lowest levels, neither spermatids nor spermatozoa were present in the homozygous testes, but when the expression of DeltaMea2 increased to 4.3% of the wt level, high sperm production was restored and a sporadic (1/22) fertile homozygous male was obtained. The earliest apoptotic degeneration of pachytene spermatocytes evidenced at 17 dpp in homozygous testes in some discrete seminiferous tubules was preceded by DeltaMea2 expression in a variegated fashion at 16 dpp. These results consistently indicated that in homozygous testes, the pachytene spermatocytes which failed to express DeltaMea2 may undergo apoptotic degeneration. Golga3/Mea2, and DeltaMea2 in homozygotes, in a certain excessive amount may be important for survival of pachytene spermatocytes in the mouse. 相似文献
24.
25.
Bukan N Sözen S Coskun U Sancak B Günel N Bozkirli I Senocak C 《European cytokine network》2003,14(3):163-167
BACKGROUND: Both interleukin-18 and nitric oxide are multifunctional molecules that are involved in the different steps of carcinogenesis. METHODS: In the present study, we measured serum interleukin-18 and nitric oxide activity in 51 bladder cancer patients with different tumor stage and grade, and in 8 healthy controls. Serum nitrite-nitrate levels were measured as an index of nitric oxide generation. RESULTS: Serum interleukin-18 levels were significantly higher in bladder cancer patients when compared to the control subjects (p > 0.05). Serum interleukin-18 levels were found to be higher in patients with Ta stage than patients with T1 and T2, T3, T4 stages and in patients with grade 1 tumors than patients with grade 2 and grade 3 tumors, but this was not statistically significant (p > 0.05). There was no significant difference in serum nitrite + nitrate levels between bladder cancer patients and control subjects. CONCLUSIONS: Elevated serum interleukin-18 levels in bladder carcinoma patients may be a result of host defence mechanism against the growth and progression of bladder cancer cells. 相似文献
26.
Lipid peroxidation and scavenging enzyme levels in the liver of streptozotocin-induced diabetic rats
Bukan N Sancak B Yavuz O Koca C Tutkun F Ozçelikay AT Altan N 《Indian journal of biochemistry & biophysics》2003,40(6):447-450
In this study, alterations in the liver antioxidant enzymes status and lipid peroxidation in short-term (8-weeks) and long-term (24-weeks) diabetic rats were examined. Glutathione peroxidase (GSH-Px) activity and malondialdehyde (MDA) levels were significantly increased, but superoxide dismutase (SOD) activity was significantly reduced in 8-weeks diabetic rats, compared to control. Catalase (CAT) activity, however, was found unchanged. In 24-weeks diabetic rats, while GSH-Px activity was unchanged, but SOD and CAT activities and MDA levels were significantly increased, compared to control. These results suggest that diabetes-induced alterations in tissue antioxidant system may reflect a generalized increase in tissue oxidative stress. It can be concluded that lipid peroxidation and antioxidant enzyme levels are elevated in diabetic condition. Hence, diabetes mellitus, if left untreated, may increase degenerative processes due to accumulation of oxidative free radicals. 相似文献
27.
The toxic effect of vincristine on the apical cells of the rat caput epididymis was investigated. The drug was administered at 20 and 40 microg/kg body weight daily for 15 days. Light microscopy using semithin sections, and transmission electron microscopy, of the caput epididymis were undertaken. The results revealed that the basal region of the apical cell was in contact with the basement membrane and the luminal end took part in endocytosis. The apical cells reflected a dose-dependent response to vincristine (VCR) treatment. In general the changes included protrusion of the apical ends deep into the lumen, with the nucleus of the cell located in such protruded ends, and an increase in the abundance of lysosomal bodies and multivesicular bodies. These changes reflected the physiological response of the apical cell to VCR treatment rather than toxic manifestations. 相似文献
28.
Ashini Bolia Brian W. Woodrum Angelo Cereda Melissa A. Ruben Xu Wang S. Banu Ozkan Giovanna Ghirlanda 《Biophysical journal》2014
Cyanovirin-N (CVN), a cyanobacterial lectin, exemplifies a class of antiviral agents that inhibit HIV by binding to the highly glycosylated envelope protein gp120. Here, we investigate the energetics of glycan recognition using a computationally inexpensive flexible docking approach, backbone perturbation docking (BP-Dock). We benchmarked our method using two mutants of CVN: P51G-m4-CVN, which binds dimannose with high affinity through domain B, and CVN(mutDB), in which binding to domain B has been abolished through mutation of five polar residues to small nonpolar side chains. We investigated the energetic contribution of these polar residues along with the additional position 53 by docking dimannose to single-point CVN mutant models. Analysis of the docking simulations indicated that the E41A/G and T57A mutations led to a significant decrease in binding energy scores due to rearrangements of the hydrogen-bond network that reverberated throughout the binding cavity. N42A decreased the binding score to a level comparable to that of CVN(mutDB) by affecting the integrity of the local protein structure. In contrast, N53S resulted in a high binding energy score, similar to P51G-m4-CVN. Experimental characterization of the five mutants by NMR spectroscopy confirmed the binding affinity pattern predicted by BP-Dock. Despite their mostly conserved fold and stability, E41A, E41G, and T57A displayed dissociation constants in the millimolar range. N53S showed a binding constant in the low micromolar range, similar to that observed for P51G-m4-CVN. No binding was observed for N42A. Our results show that BP-Dock is a useful tool for rapidly screening the relative binding affinity pattern of in silico-designed mutants compared with wild-type, supporting its use to design novel mutants with enhanced binding properties. 相似文献
29.
Kirthiram K. Sivakumar Jone A. Stanley Joe A. Arosh Melissa E. Pepling Robert C. Burghardt Sakhila K. Banu 《Developmental biology》2014
Hexavalent chromium (CrVI), one of the more toxic heavy metals, is widely used in more than 50 industries such as chrome plating, welding, wood processing and tanneries. As one of the world?s leading producers of chromium compounds, the U.S. is facing growing challenges in protecting human health against multiple adverse effects of CrVI. CrVI is rapidly converted to CrIII intracellularly, and can induce apoptosis through different mechanisms. Our previous studies demonstrated postnatal exposure to CrVI results in a delay or arrest in follicle development and puberty. Pregnant rats were treated with 25 ppm potassium dichromate (CrVI) from gestational day (GD) 9.5 to 14.5 through drinking water, placentae were removed on GD 20, and total Cr was estimated in the placentae; ovaries were removed from the F1 offspring on postnatal day (PND)-1 and various analyses were performed. Our results show that gestational exposure to CrVI resulted in (i) increased Cr concentration in the placenta, (ii) increased germ cell apoptosis by up-regulating p53/p27–Bax–caspase-3 proteins and by increasing p53–SOD-2 co-localization; (iii) accelerated germ cell cyst (GCC) breakdown; (iv) advanced primordial follicle assembly and primary follicle transition and (v) down regulation of p-AKT, p-ERK and XIAP. As a result of the above events, CrVI induced early reproductive senescence and decrease in litter size in F1 female progeny. 相似文献
30.
Muhammad Ajmal Waqas Ahmed Ahmed Sadeque Syeda Hafiza Benish Ali Syed Habib Bokhari Nuzhat Ahmed Raheel Qamar 《Molecular biology reports》2010,37(8):3869-3875
Familial Hypercholesterolemia (FH) results in elevated levels of blood lipids including total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) with normal triglycerides (TG). This disease is one of the major contributors towards an early onset of coronary heart disease (CHD). The aim of the present study was to identify the genes responsible for causing FH in Pakistani population, for this purpose a large consanguineous FH family was selected for genetic analysis. Serum lipid levels, including TC, TG, LDL-C and high density lipoprotein cholesterol (HDL-C), were determined in patients and healthy controls. In order to find the causative mutation in this family, direct sequencing of the low density lipoprotein receptor (LDLR) gene was performed. In addition the part of the Apolipoprotein-B (APOB) gene containing the mutations R3500Q and R3500W was also sequenced. Affected individuals of the family were found to have raised TC and LDL-C levels. Sequencing revealed an insertion mutation (c.2416_2417InsG) in exon 17 of the LDLR gene in all the affected individuals of the family. Common FH causing APOB mutations were not present in this family. Heterozygous individuals had TC levels ranging from ~300–500 mg/dl and the only homozygous individual with typical xanthomas had TC levels exceeding 900 mg/dl. This is the first report of a known LDLR gene mutation causing FH in the Pakistani population. Despite a large heterogeneity of LDLR mutations there are still some common mutations which are responsible for FH throughout the world. 相似文献