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51.
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Hanessian S Vinci V Auzzas L Marzi M Giannini G 《Bioorganic & medicinal chemistry letters》2006,16(18):4784-4787
Analogues of suberoylanilide hydroxamic acid (SAHA) were prepared by replacing the Zn-binding group with squaric acid, N-hydroxyurea, and 4-hydroxymethyl oxazoline units, also varying the length of the aliphatic chain. No inhibitory activity on HDAC was observed below 1.0 microM and no cytotoxic activity on different tumor cell lines was seen below 20.0 microM. 相似文献
53.
Elizabeth Buescher Tilman Achberger Idris Amusan Anthony Giannini Cherie Ochsenfeld Ana Rus Brett Lahner Owen Hoekenga Elena Yakubova Jeffrey F. Harper Mary Lou Guerinot Min Zhang David E. Salt Ivan R. Baxter 《PloS one》2010,5(6)
Controlling elemental composition is critical for plant growth and development as well as the nutrition of humans who utilize plants for food. Uncovering the genetic architecture underlying mineral ion homeostasis in plants is a critical first step towards understanding the biochemical networks that regulate a plant''s elemental composition (ionome). Natural accessions of Arabidopsis thaliana provide a rich source of genetic diversity that leads to phenotypic differences. We analyzed the concentrations of 17 different elements in 12 A. thaliana accessions and three recombinant inbred line (RIL) populations grown in several different environments using high-throughput inductively coupled plasma- mass spectroscopy (ICP-MS). Significant differences were detected between the accessions for most elements and we identified over a hundred QTLs for elemental accumulation in the RIL populations. Altering the environment the plants were grown in had a strong effect on the correlations between different elements and the QTLs controlling elemental accumulation. All ionomic data presented is publicly available at www.ionomicshub.org. 相似文献
54.
Poupak Fallahi Riccardo Giannini Paolo Miccoli Alessandro Antonelli Fulvio Basolo 《Current Genomics》2014,15(3):171-177
“The incidence of thyroid cancer, the most common endocrine malignancy, is rising. The two most common types of thyroid cancer are papillary and follicular” thyroid carcinomas. “Fine-needle aspiration (FNA) of thyroid nodules” can permit to detect many genetic mutations and other molecular alterations, including RAS and BRAF point mutations, PAX8/peroxisome proliferator-activated receptor (PPAR)γ and “RET/PTC rearrangements, occurring in thyroid papillary and follicular carcinomas” (more than 70% of cases), which can be used successfully to improve the diagnosis “and the management of patients with thyroid nodules”. The most extensive experience has been accumulated with “the diagnostic use of BRAF mutation”, which is highly specific for malignancy. “Testing FNA samples for a panel of mutations” that typically includes RAS, BRAF, PAX8/PPARγ and RET/PTC could permit to achieve the biggest diagnostic impact. “The accuracy of cancer diagnosis in thyroid nodules could be improved significantly using these and other emerging molecular markers”. 相似文献
55.
Fasinu Pius S Tekwani Babu L Nanayakkara NP Dhammika Avula Bharathi Herath HMT Bandara Wang Yan-Hong Adelli Vijender R Elsohly Mahmoud A Khan Shabana I Khan Ikhlas A Pybus Brandon S Marcsisin Sean R Reichard Gregory A McChesney James D Walker Larry A 《Malaria journal》2014,13(1):1-12
Given the threat of resistance of human malaria parasites, including to artemisinin derivatives, new agents are needed. Chloroquine (CQ) has been the most widely used anti-malarial, and new analogs (CQAns) presenting alkynes and side chain variations with high antiplasmodial activity were evaluated. Six diaminealkyne and diaminedialkyne CQAns were evaluated against CQ-resistant (CQ-R) (W2) and CQ-sensitive (CQ-S) (3D7) Plasmodium falciparum parasites in culture. Drug cytotoxicity to a human hepatoma cell line (HepG2) evaluated, allowed to calculate the drug selectivity index (SI), a ratio of drug toxicity to activity in vitro. The CQAns were re-evaluated against CQ-resistant and -sensitive P. berghei parasites in mice using the suppressive test. Docking studies with the CQAns and the human (Hss LDH) or plasmodial lactate dehydrogenase (Pf LDH) enzymes, and, a β-haematin formation assay were performed using a lipid as a catalyst to promote crystallization in vitro. All tested CQAns were highly active against CQ-R P. falciparum parasites, exhibiting half-maximal inhibitory concentration (IC50) values below 1 μΜ. CQAn33 and CQAn37 had the highest SIs. Docking studies revealed the best conformation of CQAn33 inside the binding pocket of Pf LDH; specificity between the residues involved in H-bonds of the Pf LDH with CQAn37. CQAn33 and CQAn37 were also shown to be weak inhibitors of Pf LDH. CQAn33 and CQAn37 inhibited β-haematin formation with either a similar or a 2-fold higher IC50 value, respectively, compared with CQ. CQAn37 was active in mice with P. berghei, reducing parasitaemia by 100%. CQAn33, -39 and -45 also inhibited CQ-resistant P. berghei parasites in mice, whereas high doses of CQ were inactive. The presence of an alkyne group and the size of the side chain affected anti-P. falciparum activity in vitro. Docking studies suggested a mechanism of action other than Pf LDH inhibition. The β-haematin assay suggested the presence of an additional mechanism of action of CQAn33 and CQAn37. Tests with CQAn34, CQAn37, CQAn39 and CQAn45 confirmed previous results against P. berghei malaria in mice, and CQAn33, 39 and 45 were active against CQ-resistant parasites, but CQAn28 and CQAn34 were not. The result likely reflects structure-activity relationships related to the resistant phenotype. 相似文献
56.
Walter P. Maksymowych Christos A. Gabriel Lorie Luyrink Hector Melin-Aldana Maruja Elma Edward H. Giannini Daniel J. Lovell Catherine Van Kerckhove Jeffrey Leiden Edmund Choi David N. Glass 《Immunogenetics》1992,35(4):257-262
This report demonstrates a T-cell receptor (Tcr) restriction fragment length polymorphism, defined by a Tcrb-V6.1 gene probe and Bgl II restriction enzyme, to be absolutely correlated with allelic variation in the coding sequence of a Tcrb-V6.1 gene. A pair of non-conservative amino acid substitutions distinguish the Tcrb-V6.1 allelic variants. An association of this Tcrb-V6.1 gene allelic variant with one form of juvenile rheumatoid arthritis (JRA) was established in a cohort of 126 patients. The association was observed in patients possessing the HLA-DQA1*0101 gene. Among HLA-DQA*0101 individuals, 19 of 26 patients (73.1%) carried one particular Tcrb-V6.1 gene allele as opposed to 11 of 33 controls (33%; p<0.005). Haplotypes carrying this HLA gene have previously been shown to confer increased risk for progression of arthritis in JRA. This demonstration of a disease-associated Tcrb-V gene allelic variant has not, to our knowledge, been previously reported and supports the contribution of polymorphism in the Tcr variable region genomic repertoire to human autoimmune disease.The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession numbers M67511 for V6.1A and M67512 for V6.1B. 相似文献
57.
58.
Most extant New World marsupials belong in the Didelphidae, which comprises ca. 110 currently recognized species of opossums. Didelphids are small mammals with their mean body mass, at species level, ranging from ca. 7 g to 2.2 kg. The largest species belong in a single clade, while substantial variation remains scattered across the remaining groups. We seek out to explore the details of this mass variation in an evolutionary framework. To this end, we first reconstructed the phylogeny of didelphids based on an extensive, although fragmentary sample of sequences from ten genes. We recovered a fully resolved, highly robust phylogeny that tested and confirmed most previously reported groupings, providing a simultaneous depiction of phylogenetic relationships for 81 % of currently recognized species and all relevant supra-specific clades. As much as 69 % of total body mass variation in didelphids was explained by this phylogenetic hypothesis. Mapped on it, mass variation evolved as much as 6.8 kg of total changes, starting from a reconstructed ancestral body mass range of 22–33 g. No single, family-wide pattern was evident; in fact, the dominant pattern for mass variation was that of increases in body mass along a few successive branches, or phyletic giantism, followed by apomorphic nanism, i.e., decreases localized in single terminal branches. Phyletic trends indicated the persistence of gradual, directional changes along considerable spans of geological time and show that substantial variation of interest resides in this and perhaps most groups of small mammals. 相似文献
59.
Grape seeds (GS) are one of the most important by-products of the winery and grape juice industry. GS contain a vast array of health-giving metabolites, including several polyphenols known for their remarkable antioxidant activity. In this study, it has been evaluated the nutraceutical potential of seeds from 15 grapevine cultivars/clones in terms of total phenols, monomeric, dimer, polymeric, gallate esters flavan 3-ols composition and in vitro antiradical activity. Considerable quali-quantitative differences in polyphenol content and AA had been observed among GS from different cultivars/clones collected in 2013 and 2014. In most of the investigated cultivars/clones, the better values of TP, FL and AA were recorded in GS collected in 2014. The polymeric procyanidins were significantly higher in 2014 in all the cultivars, while the gallate esters were significantly higher in 2013. These differences can be attributed to different climatic conditions in 2013 and 2014. In conclusion, the data here reported help to identify the best source of GS for the recovery of bioactive polyphenols and to valorize these waste materials. 相似文献
60.
André L. Acosta Tereza C. Giannini Vera L. Imperatriz-Fonseca Antonio M. Saraiva 《PloS one》2016,11(2)
The ecological impacts of alien species invasion are a major threat to global biodiversity. The increasing number of invasion events by alien species and the high cost and difficulty of eradicating invasive species once established require the development of new methods and tools for predicting the most susceptible areas to invasion. Invasive pollinators pose serious threats to biodiversity and human activity due to their close relationship with many plants (including crop species) and high potential competitiveness for resources with native pollinators. Although at an early stage of expansion, the bumblebee species Bombus terrestris is becoming a representative case of pollinator invasion at a global scale, particularly given its high velocity of invasive spread and the increasing number of reports of its impacts on native bees and crops in many countries. We present here a methodological framework of habitat suitability modeling that integrates new approaches for detecting habitats that are susceptible to Bombus terrestris invasion at a global scale. Our approach did not include reported invaded locations in the modeling procedure; instead, those locations were used exclusively to evaluate the accuracy of the models in predicting suitability over regions already invaded. Moreover, a new and more intuitive approach was developed to select the models and evaluate different algorithms based on their performance and predictive convergence. Finally, we present a comprehensive global map of susceptibility to Bombus terrestris invasion that highlights priority areas for monitoring. 相似文献