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101.
102.
Sana Aissi Marie-Pierre Buisine Farid Zerimech Nadia Kourda Amel Moussa Mohamed Manai Nicole Porchet 《Molecular biology reports》2014,41(3):1807-1813
Loss of TP53 function through gene mutation is a critical event in the development and progression of colorectal cancer (CRC). Here we examined 51 primary CRC tumors from Tunisia for mutations in TP53 exons 4–9 using PCR-direct sequencing. TP53 status and mutation site/type were than correlated with nuclear protein accumulation, familial and clinicopathologic variables and data on KRAS mutations and microsatellite instability (MSI-H). The TP53 mutation analysis was possible in the tumor of 47 patients and a deleterious somatic mutation has been detected in 59.6 % of the patients (28/47) including 20 (71.4 %) missense mutations, 7 nonsense mutations (25 %) and 1 (3.6 %) frameshift mutation. 89.3 % (25/28) of the detected mutations were in exons 5–8, whereas 10.7 % (3/28) were in exon 4. Among the 27 non frameshift mutations, 89 % (24/27) were transitions and 11 % (3/27) were transversions. 64.3 % (18/27) of the altered amino acids corresponded to arginine. 74 % (20/27) were G>C to A>T transitions, and more than half (14/27) occur at hotspots codons with CpG sites. TP53 mutations correlated closely with TP53 accumulation (p = 0.0090) and inversely with MSI phenotype (p = 0.0658). A KRAS somatic mutation was identified in 25 % (7/28) of the TP53 mutated tumors. All these mutations were G>A transitions in codon 12 and all the tumors with combined alterations but one were distally located and MSS. In conclusion, frequency and types of TP53 mutations and correlations with TP53 protein accumulation, and MSI were as reported for non-Tunisian patients. However, no significant associations have been detected between TP53 mutations and clinicopathological data in Tunisian patients as previously reported. 相似文献
103.
Irreversible electroporation (IRE) is a novel technique that deals with killing undesirable cells, mainly cancer cells, directly without using any cytotoxic drugs. Commonly in this technique very high electric field up to 1000?V/cm is used but for very short exposure time (nanoseconds). Low electric fields (LEFs) are used before to internalize molecules and drugs inside the cells (electroendocytosis) but mainly not in killing the cells. The aim of this work is to determine the ability of using LEFs to kill cancer cells (Hela cells). The Physics idea is in making LEFs energy equivalent to IRE energy. Four IRE protocols were selected to represent very high, high, moderate and mild voltages IRE, then we make equivalent energy for each of these protocols using different LEFs’ parameters of different amplitudes (7, 10, 14 and 20?V), different pulse numbers (40, 80, 160 and 320 pulses), different frequencies from 0.5 to 106.86?Hz and different pulse widths from 9.38 to 2000?ms. Each of the calculated LEF equivalent to IRE was applied on Hela cell line. The results show complete destruction of the cancer cells for all the tested exposure protocols. This damage was not due to thermal effect because the measured temperature was not changed before and after the exposure. The possible effect mechanism is discussed. It was concluded that the lethal effect on the cancer cells can be achieved using LEFs if the same energy equivalent to IRE is used. This work will help in using low-risk drug-free techniques in cancer treatment. 相似文献
104.
Mehdi Mehrali Ehsan Moghaddam Seyed Farid Seyed Shirazi Saeid Baradaran Mohammad Mehrali Sara Tahan Latibari Hendrik Simon Cornelis Metselaar Nahrizul Adib Kadri Keivan Zandi Noor Azuan Abu Osman 《PloS one》2014,9(9)
Calcium silicate (CaSiO3, CS) ceramic composites reinforced with graphene nanoplatelets (GNP) were prepared using hot isostatic pressing (HIP) at 1150°C. Quantitative microstructural analysis suggests that GNP play a role in grain size and is responsible for the improved densification. Raman spectroscopy and scanning electron microscopy showed that GNP survived the harsh processing conditions of the selected HIP processing parameters. The uniform distribution of 1 wt.% GNP in the CS matrix, high densification and fine CS grain size help to improve the fracture toughness by ∼130%, hardness by ∼30% and brittleness index by ∼40% as compared to the CS matrix without GNP. The toughening mechanisms, such as crack bridging, pull-out, branching and deflection induced by GNP are observed and discussed. The GNP/CS composites exhibit good apatite-forming ability in the simulated body fluid (SBF). Our results indicate that the addition of GNP decreased pH value in SBF. Effect of addition of GNP on early adhesion and proliferation of human osteoblast cells (hFOB) was measured in vitro. The GNP/CS composites showed good biocompatibility and promoted cell viability and cell proliferation. The results indicated that the cell viability and proliferation are affected by time and concentration of GNP in the CS matrix. 相似文献
105.
Alkaptonuria is often diagnosed clinically with episodes of dark urine, biochemically by the accumulation of peripheral homogentisic acid and molecularly by the presence of mutations in the homogentisate 1,2-dioxygenase gene (HGD). Alkaptonuria is invariably associated with HGD mutations, which consist of single nucleotide variants and small insertions/deletions. Surprisingly, the presence of deletions beyond a few nucleotides among over 150 reported deleterious mutations has not been described, raising the suspicion that this gene might be protected against the detrimental mechanisms of gene rearrangements. The quest for an HGD mutation in a proband with AKU revealed with a SNP array five large regions of homozygosity (5–16 Mb), one of which includes the HGD gene. A homozygous deletion of 649 bp deletion that encompasses the 72 nucleotides of exon 2 and surrounding DNA sequences in flanking introns of the HGD gene was unveiled in a proband with AKU. The nature of this deletion suggests that this in-frame deletion could generate a protein without exon 2. Thus, we modeled the tertiary structure of the mutant protein structure to determine the effect of exon 2 deletion. While the two β-pleated sheets encoded by exon 2 were missing in the mutant structure, other β-pleated sheets are largely unaffected by the deletion. However, nine novel α-helical coils substituted the eight coils present in the native HGD crystal structure. Thus, this deletion results in a deleterious enzyme, which is consistent with the proband’s phenotype. Screening for mutations in the HGD gene, particularly in the Middle East, ought to include this exon 2 deletion in order to determine its frequency and uncover its origin. 相似文献
106.
Arnaud Goessens Behara Satyanarayana Tom Van der Stocken Melissa Quispe Zuniga Husain Mohd-Lokman Ibrahim Sulong Farid Dahdouh-Guebas 《PloS one》2014,9(8)
Matang Mangrove Forest Reserve (MMFR) in Peninsular Malaysia is under systematic management since 1902 and still considered as the best managed mangrove forest in the world. The present study on silvimetrics assessed the ongoing MMFR forest management, which includes a first thinning after 15 years, a second thinning after 20 years and clear-felling of 30-year old forest blocks, for its efficiency and productivity in comparison to natural mangroves. The estimated tree structural parameters (e.g. density, frequency) from three different-aged mangrove blocks of fifteen (MF15), twenty (MF20), and thirty (MF30) years old indicated that Bruguiera and Excoecaria spp. did not constitute a significant proportion of the vegetation (<5%), and hence the results focused majorly on Rhizophora apiculata. The density of R. apiculata at MF15, MF20 and MF30 was 4,331, 2,753 and 1,767 stems ha−1, respectively. In relation to ongoing practices of the artificial thinnings at MMFR, the present study suggests that the first thinning could be made earlier to limit the loss of exploitable wood due to natural thinning. In fact, the initial density at MF15 was expected to drop down from 6,726 to 1,858 trees ha−1 before the first thinning. Therefore the trees likely to qualify for natural thinning, though having a smaller stem diameter, should be exploited for domestic/commercial purposes at an earlier stage. The clear-felling block (MF30) with a maximum stem diameter of 30 cm was estimated to yield 372 t ha−1 of the above-ground biomass and suggests that the mangrove management based on a 30-year rotation is appropriate for the MMFR. Since Matang is the only iconic site that practicing sustainable wood production, it could be an exemplary to other mangrove locations for their improved management. 相似文献
107.
Mohd Askandar Iqbal Farid Ahmad Siddiqui Noor Chaman Vibhor Gupta Bhupender Kumar Prakasam Gopinath Rameshwar N. K. Bamezai 《The Journal of biological chemistry》2014,289(12):8098-8105
The present study was designed to examine the functional relevance of two heterozygous mutations (H391Y and K422R), observed earlier by us in the Bloom syndrome condition. Cells stably expressing exogenous wild-type or mutant PKM2 (K422R or H391Y) or co-expressing both wild type and mutant (PKM2-K422R or PKM2-H391Y) were assessed for cancer metabolism and tumorigenic potential. Interestingly, cells co-expressing PKM2 and mutant (K422R or H391Y) showed significantly aggressive cancer metabolism as compared with cells expressing either wild-type or mutant PKM2 independently. A similar trend was observed for oxidative endurance, tumorigenic potential, cellular proliferation, and tumor growth. These observations signify the dominant negative nature of mutations. Remarkably, PKM2-H391Y co-expressed cells showed a maximal effect on all the studied parameters. Such a dominant negative impaired function of PKM2 in tumor development is not known; this study demonstrates for the first time the possible predisposition of Bloom syndrome patients with impaired PKM2 activity to cancer and the importance of studying genetic variations in PKM2 in the future to understand their relevance in cancer in general. 相似文献
108.
Yves Harder Daniel Schmauss Reto Wettstein José T. Ega?a Fabian Weiss Andrea Weinzierl Anna Schuldt Hans-Günther Machens Michael D. Menger Farid Rezaeian 《Journal of visualized experiments : JoVE》2014,(93)
Despite profound expertise and advanced surgical techniques, ischemia-induced complications ranging from wound breakdown to extensive tissue necrosis are still occurring, particularly in reconstructive flap surgery. Multiple experimental flap models have been developed to analyze underlying causes and mechanisms and to investigate treatment strategies to prevent ischemic complications. The limiting factor of most models is the lacking possibility to directly and repetitively visualize microvascular architecture and hemodynamics. The goal of the protocol was to present a well-established mouse model affiliating these before mentioned lacking elements. Harder et al. have developed a model of a musculocutaneous flap with a random perfusion pattern that undergoes acute persistent ischemia and results in ~50% necrosis after 10 days if kept untreated. With the aid of intravital epi-fluorescence microscopy, this chamber model allows repetitive visualization of morphology and hemodynamics in different regions of interest over time. Associated processes such as apoptosis, inflammation, microvascular leakage and angiogenesis can be investigated and correlated to immunohistochemical and molecular protein assays. To date, the model has proven feasibility and reproducibility in several published experimental studies investigating the effect of pre-, peri- and postconditioning of ischemically challenged tissue. 相似文献
109.
Markus Fabrizii Farid Moinfar Herbert F. Jelinek Audrey Karperien Helmut Ahammer 《PloS one》2014,9(10)
Introduction
Cervical intraepithelial neoplasias (CIN) represent precursor lesions of cervical cancer. These neoplastic lesions are traditionally subdivided into three categories CIN 1, CIN 2, and CIN 3, using microscopical criteria. The relation between grades of cervical intraepithelial neoplasia (CIN) and its fractal dimension was investigated to establish a basis for an objective diagnosis using the method proposed.Methods
Classical evaluation of the tissue samples was performed by an experienced gynecologic pathologist. Tissue samples were scanned and saved as digital images using Aperio scanner and software. After image segmentation the box counting method as well as multifractal methods were applied to determine the relation between fractal dimension and grades of CIN. A total of 46 images were used to compare the pathologist''s neoplasia grades with the predicted groups obtained by fractal methods.Results
Significant or highly significant differences between all grades of CIN could be found. The confusion matrix, comparing between pathologist''s grading and predicted group by fractal methods showed a match of 87.1%. Multifractal spectra were able to differentiate between normal epithelium and low grade as well as high grade neoplasia.Conclusion
Fractal dimension can be considered to be an objective parameter to grade cervical intraepithelial neoplasia. 相似文献110.
Yusuf Talha Tamer Ilona Gaszek Marinelle Rodrigues Fatma Sevde Coskun Michael Farid Andrew Y Koh William Russ Erdal Toprak 《Molecular biology and evolution》2021,38(10):4493
Bacteriophages and bacterial toxins are promising antibacterial agents to treat infections caused by multidrug-resistant (MDR) bacteria. In fact, bacteriophages have recently been successfully used to treat life-threatening infections caused by MDR bacteria (Schooley RT, Biswas B, Gill JJ, Hernandez-Morales A, Lancaster J, Lessor L, Barr JJ, Reed SL, Rohwer F, Benler S, et al. 2017. Development and use of personalized bacteriophage-based therapeutic cocktails to treat a patient with a disseminated resistant Acinetobacter baumannii infection. Antimicrob Agents Chemother. 61(10); Chan BK, Turner PE, Kim S, Mojibian HR, Elefteriades JA, Narayan D. 2018. Phage treatment of an aortic graft infected with Pseudomonas aeruginosa. Evol Med Public Health. 2018(1):60–66; Petrovic Fabijan A, Lin RCY, Ho J, Maddocks S, Ben Zakour NL, Iredell JR, Westmead Bacteriophage Therapy Team. 2020. Safety of bacteriophage therapy in severe Staphylococcus aureus infection. Nat Microbiol. 5(3):465–472). One potential problem with using these antibacterial agents is the evolution of resistance against them in the long term. Here, we studied the fitness landscape of the Escherichia coli TolC protein, an outer membrane efflux protein that is exploited by a pore forming toxin called colicin E1 and by TLS phage (Pagie L, Hogeweg P. 1999. Colicin diversity: a result of eco-evolutionary dynamics. J Theor Biol. 196(2):251–261; Andersen C, Hughes C, Koronakis V. 2000. Chunnel vision. Export and efflux through bacterial channel-tunnels. EMBO Rep. 1(4):313–318; Koronakis V, Andersen C, Hughes C. 2001. Channel-tunnels. Curr Opin Struct Biol. 11(4):403–407; Czaran TL, Hoekstra RF, Pagie L. 2002. Chemical warfare between microbes promotes biodiversity. Proc Natl Acad Sci U S A. 99(2):786–790; Cascales E, Buchanan SK, Duché D, Kleanthous C, Lloubès R, Postle K, Riley M, Slatin S, Cavard D. 2007. Colicin biology. Microbiol Mol Biol Rev. 71(1):158–229). By systematically assessing the distribution of fitness effects of ∼9,000 single amino acid replacements in TolC using either positive (antibiotics and bile salts) or negative (colicin E1 and TLS phage) selection pressures, we quantified evolvability of the TolC. We demonstrated that the TolC is highly optimized for the efflux of antibiotics and bile salts. In contrast, under colicin E1 and TLS phage selection, TolC sequence is very sensitive to mutations. Finally, we have identified a large set of mutations in TolC that increase resistance of E. coli against colicin E1 or TLS phage without changing antibiotic susceptibility of bacterial cells. Our findings suggest that TolC is a highly evolvable target under negative selection which may limit the potential clinical use of bacteriophages and bacterial toxins if evolutionary aspects are not taken into account. 相似文献