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1.
El-Jawahri A Patel D Zhang M Mladkova N Chakravarti A 《Molecular diagnosis & therapy》2008,12(4):199-208
Gliomas are the most common primary brain tumors in adults. Anaplastic astrocytoma and glioblastoma multiforme represent malignant astrocytomas, which are the most common type of malignant gliomas. Despite research efforts in cancer therapy, the prognosis of patients with malignant gliomas remains poor. Research efforts in recent years have focused on investigating the cellular, molecular, and genetic pathways involved in the progression of malignant gliomas. As a result, biomarkers have emerged as diagnostic, predictive, and prognostic tools that have the potential to transform the field of brain tumor diagnostics. An increased understanding of the important molecular pathways that have been implicated in the progression of malignant gliomas has led to the identification of potential diagnostic, prognostic, and predictive biomarkers, some bearing clinical implications for targeted therapy. Some of the most promising biomarkers to date include loss of chromosomes 1p/19q in oligodendrogliomas and expression of O-6-methylguanine-DNA methyltransferase (MGMT) or epidermal growth factor receptor (EGFR) status in glioblastomas. Other promising biomarkers in glioma research include glial fibrillary acidic protein, galectins, Kir potassium channel proteins, angiogenesis, and apoptosis pathway markers. Research into the clinical relevance and applicability of such biomarkers has the potential to revolutionize our approach to the diagnosis and treatment of patients with malignant gliomas. 相似文献
2.
Tenzin Gayden Annabel Perez Patrice J. Persad Areej Bukhari Shilpa Chennakrishnaiah Tanya Simms Trisha Maloney Kristina Rodriguez Rene J. Herrera 《American journal of physical anthropology》2013,151(2):169-182
The Himalayan mountain range is strategically located at the crossroads of the major cultural centers in Asia, the Middle East and Europe. Although previous Y‐chromosome studies indicate that the Himalayas served as a natural barrier for gene flow from the south to the Tibetan plateau, this region is believed to have played an important role as a corridor for human migrations between East and West Eurasia along the ancient Silk Road. To evaluate the effects of the Himalayan mountain range in shaping the maternal lineages of populations residing on either side of the cordillera, we analyzed mitochondrial DNA variation in 344 samples from three Nepalese collections (Newar, Kathmandu and Tamang) and a general population of Tibet. Our results revealed a predominantly East Asian‐specific component in Tibet and Tamang, whereas Newar and Kathmandu are both characterized by a combination of East and South Central Asian lineages. Interestingly, Newar and Kathmandu harbor several deep‐rooted Indian lineages, including M2, R5, and U2, whose coalescent times from this study (U2, >40 kya) and previous reports (M2 and R5, >50 kya) suggest that Nepal was inhabited during the initial peopling of South Central Asia. Comparisons with our previous Y‐chromosome data indicate sex‐biased migrations in Tamang and a founder effect and/or genetic drift in Tamang and Newar. Altogether, our results confirm that while the Himalayas acted as a geographic barrier for human movement from the Indian subcontinent to the Tibetan highland, it also served as a conduit for gene flow between Central and East Asia. Am J Phys Anthropol 151:169–182, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
3.
Saleh I. Alqasoumi Areej M. Al-Taweel Ahmed M. Alafeefy Mostafa M. Hamed Eman Noaman Mostafa M. Ghorab 《Bioorganic & medicinal chemistry letters》2009,19(24):6939-6942
A large number of antimitotic drugs, derived from natural sources or chemically synthesized, have been identified and shown to interfere with the tubulin system. Inhibition of tubulin polymerization is among the important targets useful in the cancer therapy.The present work reports the synthesis of some novel quinoline derivatives bearing a trimethoxyphenyl moiety. The trimethoxybenzene moiety has been reported to be crucial to obtain relevant cytotoxic and antitubulin responses. All the newly synthesized compounds were evaluated for their in vitro anticancer activity. Several compounds showed interesting cytotoxic activities compared to the used reference drug. 相似文献
4.
Areej M. Abuhammad Edward D. Lowe Elizabeth Fullam Martin Noble Elspeth F. Garman Edith Sim 《蛋白质与细胞》2010,1(4):384-392
Treatment of latent tuberculosis infection remains an important goal of global TB eradication. To this end, targets that are essential for intracellular survival of Mycobacterium tuberculosis are particularly attractive. Arylamine N-acetyltransferase (NAT) represents such a target as it is, along with the enzymes encoded by the associated gene cluster, essential for mycobacterial survival inside macrophages and involved in cholesterol degradation. Cholesterol is likely to be the fuel for M. tuberculosis inside macrophages. Deleting the nat gene and inhibiting the NAT enzyme prevents survival of the microorganism in macrophages and induces cell wall alterations, rendering the mycobacterium sensitive to antibiotics to which it is normally resistant. To date, NAT from M. marinum (MMNAT) is considered the best available model for NAT from M. tuberculosis (TBNAT). The enzyme catalyses the acetylation and propionylation of arylamines and hydrazines. Hydralazine is a good acetyl and propionyl acceptor for both MMNAT and TBNAT. The MMNAT structure has been solved to 2.1 Å resolution following crystallisation in the presence of hydralazine and is compared to available NAT structures. From the mode of ligand binding, features of the binding pocket can be identified, which point to a novel mechanism for the acetylation reaction that results in a 3-methyltriazolo[3,4-a]phthalazine ring compound as product. 相似文献
5.
Areej Abuhammad Edward D. Lowe Michael A. McDonough Patrick D. Shaw Stewart Stefan A. Kolek Edith Sim Elspeth F. Garman 《Acta Crystallographica. Section D, Structural Biology》2013,69(8):1433-1446
Arylamine N‐acetyltransferase from Mycobacterium tuberculosis (TBNAT) plays an important role in the intracellular survival of the microorganism inside macrophages. Medicinal chemistry efforts to optimize inhibitors of the TBNAT enzyme have been hampered by the lack of a three‐dimensional structure of the enzyme. In this paper, the first structure of TBNAT, determined using a lone crystal produced using cross‐seeding with the homologous protein from M. marinum, is reported. Despite the similarity between the two enzymes (74% sequence identity), they show distinct physical and biochemical characteristics. The structure elegantly reveals the characteristic features of the protein surface as well as details of the active site of TBNAT relevant to drug‐discovery efforts. The crystallographic analysis of the diffraction data presented many challenges, since the crystal was twinned and the habit possessed pseudo‐translational symmetry. 相似文献
6.
Giovanni Smaldone Alessia Ruggiero Nicole Balasco Areej Abuhammad Ida Autiero Daniela Caruso Davide Esposito Giarita Ferraro Edoardo L. M. Gelardi Miguel Moreira Mussa Quareshy Maria Romano Annica Saaret Irwin Selvam Flavia Squeglia Romualdo Troisi Loes M. J. Kroon-Batenburg Luciana Esposito Rita Berisio Luigi Vitagliano 《Acta Crystallographica. Section F, Structural Biology Communications》2019,75(11):707-713
Domain swapping is a widespread oligomerization process that is observed in a large variety of protein families. In the large superfamily of substrate‐binding proteins, non‐monomeric members have rarely been reported. The arginine‐binding protein from Thermotoga maritima (TmArgBP), a protein endowed with a number of unusual properties, presents a domain‐swapped structure in its dimeric native state in which the two polypeptide chains mutually exchange their C‐terminal helices. It has previously been shown that mutations in the region connecting the last two helices of the TmArgBP structure lead to the formation of a variety of oligomeric states (monomers, dimers, trimers and larger aggregates). With the aim of defining the structural determinants of domain swapping in TmArgBP, the monomeric form of the P235GK mutant has been structurally characterized. Analysis of this arginine‐bound structure indicates that it consists of a closed monomer with its C‐terminal helix folded against the rest of the protein, as typically observed for substrate‐binding proteins. Notably, the two terminal helices are joined by a single nonhelical residue (Gly235). Collectively, the present findings indicate that extending the hinge region and conferring it with more conformational freedom makes the formation of a closed TmArgBP monomer possible. On the other hand, the short connection between the helices may explain the tendency of the protein to also adopt alternative oligomeric states (dimers, trimers and larger aggregates). The data reported here highlight the importance of evolutionary control to avoid the uncontrolled formation of heterogeneous and potentially harmful oligomeric species through domain swapping. 相似文献
7.
Areej A. Al-Khalaf 《Saudi Journal of Biological Sciences》2021,28(10):5667-5673
ObjectivesThe species Palarus latifrons (bee pirates) has been recorded in Saudi Arabia as an invasive species. This pest can destroy honey bee colonies under certain conditions. The origin of this species in Africa and it has a good ability to adapt to desert conditions. Studies on this species are very few but its current distribution in the Arabian deserts is mainly in the Arabian Gulf countries. This study presents maps for the possible expansion of this species to invade other desert areas in the Arabian countries’ under current and near-future conditions (2030).MethodsThis pest is a solitary insect with high activity during summer. It is hypothesized that summer conditions and especially temperature are the limiting factor for its distribution in the deserts. The analysis depended on generating maps based on temperatures during summer and based on two bioclimatic factors. Maxent and the geographical information system (GIS) were used to perform the analysis.Results and conclusionsAll maps showed the high ability of this pest to spread in the Gulf countries. In North Africa: south Egypt and Libya, and some parts of Algeria showed suitability for Palarus. The invasion of this pest towards North Africa can happen mostly due to trading activities with Gulf countries especially materials containing soil. Continues monitoring for the activity of Palarus in the risk areas is highly advised. 相似文献
8.
9.
Chan‐Ju Wang Nicola Laurieri Areej Abuhammad Edward Lowe Isaac Westwood Ali Ryan Edith Sim 《Acta Crystallographica. Section F, Structural Biology Communications》2010,66(1):2-7
Azoreductase 1 from Pseudomonas aeruginosa strain PAO1 (paAzoR1) catalyses the activation of the prodrug balsalazide and reduces the azo dye methyl red using reduced nicotinamide adenine dinucleotide cofactor as an electron donor. To investigate the mechanism of the enzyme, a Y131F mutation was introduced and the enzymic properties of the mutant were compared with those of the wild‐type enzyme. The crystallographic structure of the mutant with methyl red bound was solved at 2.1 Å resolution and compared with the wild‐type structure. Tyr131 is important in the architecture of the active site but is not essential for enzymic activity. 相似文献
10.
Elizabeth Fullam Akane Kawamura Helen Wilkinson Areej Abuhammad Isaac Westwood Edith Sim 《The protein journal》2009,28(6):281-293
Arylamine N-acetyltansferase (NAT) from Mycobacterium tuberculosis (TBNAT) is a potential drug target for anti-tubercular therapy. Recombinant TBNAT is much less soluble and is produced in
lower yields than the closely related NAT from Mycobacterium marinum (MMNAT). In order to explore MMNAT as a model for TBNAT in drug discovery, we compare the two mycobacterial NAT enzymes.
Two site-directed mutants of MMNAT have been prepared and characterised: MMNAT71, Tyr → Phe and MMNAT209, Met → Thr, in which
residues within 6 Å of the active-site cysteine have been replaced with the corresponding residue from TBNAT. Two chimeric
proteins have also been produced in which the third domain of MMNAT has been replaced by the third domain of TBNAT and vice
versa. The activity profile of the chimeric proteins suggests a role for the third domain in the evolutionary divergence of
NAT between these closely related mycobacterial species. 相似文献