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1.
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
2.
Ramin Ekhteiari Salmas Serdar Durdagi Mehmet Fuat Gulhan Merve Duruyurek Huda I. Abdullah 《Journal of biomolecular structure & dynamics》2018,36(3):609-620
The objective of the present study was to evaluate the effects of propolis, pollen, and caffeic acid phenethyl ester (CAPE) on tyrosine hydroxylase (TH) activity and total RNA levels of Nω-nitro-L-arginine methyl ester (L-NAME) inhibition of nitric oxide synthase in the heart, adrenal medulla, and hypothalamus of hypertensive male Sprague dawley rats. The TH activity in the adrenal medulla, heart, and hypothalamus of the rats was significantly increased in the L-NAME group vs. control (p < 0.05). Treatment with L-NAME led to a significant increase in blood pressure (BP) in the L-NAME group compared to control (p < 0.05). These data suggest that propolis, pollen, and CAPE may mediate diminished TH activity in the heart, adrenal medulla, and hypothalamus in hypertensive rats. The decreased TH activity may be due to the modulation and synthesis of catecholamines and BP effects. In addition, the binding mechanism of CAPE within the catalytic domain of TH was investigated by means of molecular modeling approaches. These data suggest that the amino acid residues, Glu429 and Ser354 of TH may play a pivotal role in the stabilization of CAPE within the active site as evaluated by molecular dynamics (MD) simulations. Gibbs binding free energy (ΔGbinding) of CAPE in complex with TH was also determined by post-processing MD analysis approaches (i.e. Poisson-Boltzmann Surface Area (MM-PBSA) method). 相似文献
3.
Chromatin, the complex of DNA and histone proteins, serves as a main integrator of cellular signals. Increasing evidence links cellular functional to chromatin state. Indeed, different metabolites are emerging as modulators of chromatin function and structure. Alterations in chromatin state are decisive for regulating all aspects of genome function and ultimately have the potential to produce phenotypic changes. Several metabolites such as acetyl-CoA, S-adenosylmethionine (SAM) or adenosine triphosphate (ATP) have now been well characterized as main substrates or cofactors of chromatin-modifying enzymes. However, there are other metabolites that can directly interact with chromatin influencing its state or that modulate the properties of chromatin regulatory factors. Also, there is a growing list of atypical enzymatic and nonenzymatic chromatin modifications that originate from different cellular pathways that have not been in the limelight of chromatin research. Here, we summarize different properties and functions of uncommon regulatory molecules originating from intermediate metabolism of lipids, carbohydrates and amino acids. Based on the various modes of action on chromatin and the plethora of putative, so far not described chromatin-regulating metabolites, we propose that there are more links between cellular functional state and chromatin regulation to be discovered. We hypothesize that these connections could provide interesting starting points for interfering with cellular epigenetic states at a molecular level. 相似文献
4.
Noor Ahmad Shaik Huda M. Al-Kreathy Ghada M. Ajabnoor Prashant Kumar Verma Babajan Banaganapalli 《Saudi Journal of Biological Sciences》2019,26(3):439-448
The somatic mutations in ATP binding cleft of the tyrosine kinase binding domain of EGFR are known to occur in 15–40% of non-small cell lung cancer (NSCLC) patients. Although first and second generation anti-EGFR inhibitors are widely used to treat these patients, their therapeutic efficacy is modest and often results in adverse effects or drug resistance. Therefore, there is a need to develop novel as well as safe anti-EGFR drugs. The rapid emergence of computational drug designing provided a great opportunity to both discover and predict the efficacy of novel EGFR inhibitors from plant sources. In the present study, we designed several chemical analogues of edible curcumin (CUCM) compound and assessed their drug likeliness, ADME and toxicity properties using a diverse range of advanced computational methods. We also have examined the structural plasticity and binding characteristics of EGFR wild-type and mutant forms (S769L and K846R) against ligand molecules like Gefitinib, native CUCM, and different CUCM analogues. Through multidimensional experimental approaches, we conclude that CUCM-36 ((1E,4Z,6E)-1-(3,4-Diphenoxyphenyl)-5-hydroxy-7-(4-hydroxy-3-phenoxyphenyl)-1,4,6-heptatrien-3-one) is the best anti-EGFR compound with high drug-likeness, ADME properties, and low toxicity properties. CUCM-36 compound has demonstrated better affinity towards both wild-type (ΔG is ?8.5?kcal/Mol) and mutant forms (V769L & K846R; ΔG for both is >?9.20?kcal/Mol) compared to natural CUCM and Gefitinib inhibitor. This study advises the future laboratory assays to develop CUCM-36 as a novel drug compound for treating EGFR positive non-small cell lung cancer patients. 相似文献
5.
DNAI2 mutations cause primary ciliary dyskinesia with defects in the outer dynein arm 总被引:1,自引:0,他引:1
6.
Huda Al-Mutlaq Janice Wheeler Helen Robertson Caroline Watchorn A. R. Morley 《The Histochemical journal》1993,25(3):219-227
Summary A monoclonal antibody reactive against amyloid P component (NCL-AMP) has been developed following immunization of mice with partially-purified human glomerular basement membranes (GBM) and standard hybridization and cloning techniques. The antibody reactivity was evaluated by enzyme-linked immunosorbent assay (ELISA) and by the indirect immunoperoxidase technique on sections of frozen and fixed human kidney and other tissues. The distribution of amyloid P component in various normal tissues is described and the possible co-localization with the Goodpasture antigen is discussed. In addition, the suitability of the antibody for detection of amyloid deposits in renal amyloidosis is demonstrated and its potential for use in other pathological conditions is considered. 相似文献
7.
The effect of white light on the malate oxidase of Sarcina lutea (Micrococcus luteus) membranes has been examined using a carotenoid-containing and a carotenoidless mutant. At least three photosensitive sites have been detected. Two of these are associated with the malate dehydrogenase complex (malate-menaquinone reductase) and are unaffected by membrane carotenoid. A third site which has been detected beyond the dehydrogenase complex, is protected by carotenoid since it can only be demonstrated in carotenoidless systems. A repair mechanism has been found for one of the two sites in the dehydrogenase complex. 相似文献
8.
COVID-19 pandemic has caused a global lockdown in many countries throughout the world. Faced with a new reality, and until a vaccine or efficient treatment is found, humanity must figure out ways to keep the economy going, on one hand, while keeping the population safe, on the other hand, especially those that are susceptible to this virus. Here, we use a Watts–Strogatz network simulation, with parameters that were drawn from what is already known about the virus, to explore five different scenarios of partial lockdown release in two geographical locations with different age distributions. We find that separating age groups by reducing interactions between them protects the general population and reduces mortality rates. Furthermore, the addition of new connections within the same age group to compensate for the lost connections outside the age group still has a strong beneficial influence and reduces the total death toll by about 62%. While complete isolation from society may be the most protective scenario for the elderly population, it would have an emotional and possibly cognitive impact that might outweigh its benefit. Therefore, we propose creating age-related social recommendations or even restrictions, thereby allowing social connections while still offering strong protection for the older population. 相似文献
9.
Experimentally characterized enhancer regions have previously been shown to display specific patterns of enrichment for several different histone modifications. We modelled these enhancer chromatin profiles in the human genome and used them to guide the search for novel enhancers derived from transposable element (TE) sequences. To do this, a computational approach was taken to analyze the genome-wide histone modification landscape characterized by the ENCODE project in two human hematopoietic cell types, GM12878 and K562. We predicted the locations of 2,107 and 1,448 TE-derived enhancers in the GM12878 and K562 cell lines respectively. A vast majority of these putative enhancers are unique to each cell line; only 3.5% of the TE-derived enhancers are shared between the two. We evaluated the functional effect of TE-derived enhancers by associating them with the cell-type specific expression of nearby genes, and found that the number of TE-derived enhancers is strongly positively correlated with the expression of nearby genes in each cell line. Furthermore, genes that are differentially expressed between the two cell lines also possess a divergent number of TE-derived enhancers in their vicinity. As such, genes that are up-regulated in the GM12878 cell line and down-regulated in K562 have significantly more TE-derived enhancers in their vicinity in the GM12878 cell line and vice versa. These data indicate that human TE-derived sequences are likely to be involved in regulating cell-type specific gene expression on a broad scale and suggest that the enhancer activity of TE-derived sequences is mediated by epigenetic regulatory mechanisms. 相似文献
10.
Sarah M. Clinton Tracy A. Bedrosian Antony D. Abraham Stanley J. Watson Huda Akil 《Hormones and behavior》2010,57(4-5):463-473
Selective breeding of rats exhibiting differences in novelty-induced locomotion revealed that this trait predicts several differences in emotional behavior. Bred High Responders (bHRs) show exaggerated novelty-induced locomotion, aggression, and psychostimulant self-administration, compared to bred Low Responders (bLRs), which are inhibited and prone to anxiety- and depression-like behavior. Our breeding studies highlight the heritability of the bHR/bLR phenotypes, although environmental factors like maternal care also shape some aspects of these traits. We previously reported that HR vs. LR mothers act differently, but it was unclear whether their behaviors were genetically driven or influenced by their pups. The present study (a) used cross-fostering to evaluate whether the bHR/bLR maternal styles are inherent to mothers and/or are modulated by pups; and (b) assessed oxytocin and oxytocin receptor mRNA expression to examine possible underpinnings of bHR/bLR maternal differences. While bHR dams exhibited less maternal behavior than bLRs during the dark/active phase, they were very attentive to pups during the light phase, spending greater time passive nursing and in contact with pups compared to bLRs. Cross-fostering only subtly changed bHR and bLR dams' behavior, suggesting that their distinct maternal styles are largely inherent to the mothers. We also found elevated oxytocin mRNA levels in the supraoptic nucleus of the hypothalamus in bHR versus bLR dams, which may play some role in driving their behavior differences. Overall these studies shed light on the interplay between the genetics of mothers and infants in driving differences in maternal style. 相似文献