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101.
Niyati Jain Christopher E. Morgan Brittany D. Rife Marco Salemi Blanton S. Tolbert 《The Journal of biological chemistry》2016,291(5):2331-2344
Splicing patterns in human immunodeficiency virus type 1 (HIV-1) are maintained through cis regulatory elements that recruit antagonistic host RNA-binding proteins. The activity of the 3′ acceptor site A7 is tightly regulated through a complex network of an intronic splicing silencer (ISS), a bipartite exonic splicing silencer (ESS3a/b), and an exonic splicing enhancer (ESE3). Because HIV-1 splicing depends on protein-RNA interactions, it is important to know the tertiary structures surrounding the splice sites. Herein, we present the NMR solution structure of the phylogenetically conserved ISS stem loop. ISS adopts a stable structure consisting of conserved UG wobble pairs, a folded 2X2 (GU/UA) internal loop, a UU bulge, and a flexible AGUGA apical loop. Calorimetric and biochemical titrations indicate that the UP1 domain of heterogeneous nuclear ribonucleoprotein A1 binds the ISS apical loop site-specifically and with nanomolar affinity. Collectively, this work provides additional insights into how HIV-1 uses a conserved RNA structure to commandeer a host RNA-binding protein. 相似文献
102.
Scandura Massimo Iacolina Laura Capitani Claudia Gazzola Andrea Mattioli Luca Apollonio Marco 《European Journal of Wildlife Research》2011,57(4):949-958
We investigated local gene flow in a high-density wolf (Canis lupus) population of the Italian Apennines, where no effective barrier to wolf dispersal was present. From 1998 to 2004 we examined
wolf carcasses and non-invasively collected samples, focusing on three mountain districts, separated by two valleys, where
wolf packs showed high spatial stability. Using nine autosomal microsatellites we successfully genotyped 177 samples, achieving
the identification of 74 wolves. Genetic relatedness steeply decreased with increasing distance between sampling areas, thus
suggesting that short-distance interpack migration is infrequent in this population. In addition, no individual from a central
pack under intensive monitoring was sampled in the range of the surrounding packs over a 4-year period. The limited short-distance
gene flow resulted in a cryptic genetic structure, which was revealed by Bayesian analysis. A different genetic cluster was
found in each of the three mountain areas, and a small proportion of first-generation immigrants was detected. Overall, the
present study suggests that local genetic differentiation in Italian wolves might arise from high spatial stability of packs
and can be favoured by a combination of long-range dispersal, the attitude to mate between unrelated individuals and a high
young mortality rate. 相似文献
103.
Biological Effects of Insulin and Its Analogs on Cancer Cells With Different Insulin Family Receptor Expression 下载免费PDF全文
104.
Lucia Panzella Paola Manini Giuseppe Monfrecola Marco D'Ischia Alessandra Napolitano 《Pigment cell & melanoma research》2007,20(2):128-133
A procedure for analysis of melanin‐pigmented tissues based on alkaline hydrogen peroxide degradation coupled with high‐performance liquid chromatography (HPLC) ultraviolet determination of pyrrole‐2,3,5‐tricarboxylic acid (PTCA) for eumelanin and 6‐(2‐amino‐2‐carboxyethyl)‐2‐carboxy‐4‐hydroxybenzothiazole (BTCA) and 1,3‐thiazole‐2,4,5‐tricarboxylic acid for pheomelanin was recently developed. Despite advantages related to the degradation conditions and sample handling, a decrease of the reproducibility and resolution was observed after several chromatographic runs. We report herein an improved chromatographic methodology for simultaneous determination of PTCA and BTCA as representative markers of eumelanin and pheomelanin, respectively, based on the use of an octadecylsilane column with polar end‐capping with 1% formic acid (pH 2.8)/methanol as the eluant. The method requires conventional HPLC equipments and gives very good peak shapes and resolution, without need of ion pair reagents or high salt concentrations in the mobile phase. The intra‐assay precision of the analytical runs was satisfactory with CV values ≤4.0% (n = 5) for the two markers which did not exceed 8% after 50 consecutive injections on the column over 1 week. The peak area ratios at 254 and 280 nm (A280/A254: PTCA = 1.1, BTCA = 0.6) proved a valuable parameter for reliable identification of the structural markers even in the most complex degradation mixtures. The method can be applied to various eumelanin and pheomelanin pigmented tissues, including mammalian hair, skin and irides, and is amenable to be employed in population screening studies. 相似文献
105.
Iman Azimi Jack U. Flanagan Ralph J. Stevenson Marco Inserra Irina Vetter Gregory R. Monteith William A. Denny 《Bioorganic & medicinal chemistry》2017,25(1):440-449
The Orai1 Ca2+ permeable ion channel is an important component of store operated Ca2+ entry (SOCE) in cells. It’s over-expression in basal molecular subtype breast cancers has been linked with poor prognosis, making it a potential target for drug development. We pharmacologically characterised a number of reported inhibitors of SOCE in MDA-MB-231 breast cancer cells using a convenient Fluorescence Imaging Plate Reader (FLIPR) assay, and show that the rank order of their potencies in this assay is the same as those reported in a wide range of published assays. The assay was also used in a screening project seeking novel inhibitors. Following a broad literature survey of classes of calcium channel inhibitors we used simplified ligand structures to query the ZINC on-line database, and following two iterations of refinement selected a novel Orai1-selective dichlorophenyltriazole hit compound. Analogues of this were synthesized and evaluated in the FLIPR assay to develop structure–activity relationships (SAR) for the three domains of the hit; triazole (head), dichlorophenyl (body) and substituted phenyl (tail). For this series, the results suggested the need for a lipophilic tail domain and an out-of-plane twist between the body and tail domains. 相似文献
106.
Fernanda Veruska Narciso José A. Barela Stefane A. Aguiar Adriana N. S. Carvalho Sergio Tufik Marco Túlio de Mello 《PloS one》2016,11(4)
The purpose of the study was to investigate the effects of shift work on the psychomotor and postural performance of night workers. The study included 20 polysomnography technicians working schedule of 12-h night shift by 36-h off. On the first day of protocol, the body mass and height were measured, and an actigraph was placed on the wrist of each participant. On the second day of protocol, sleepiness by Karolinska Sleepiness Scale, postural control by force platform (30 seconds) and psychomotor performance by Psychomotor Vigilance Task (10 minutes) were measured before and after 12-h night work. Results showed that after 12-h night work, sleepiness increased by 59% (p<0.001), postural control variables increased by 9% (p = 0.048), and 14% (p = 0.006). Mean reaction time, and the number of lapses of attention increased by 13% (p = 0.006) and 425% (p = 0.015), respectively, but the mean reciprocal reaction time decreased by 7%. In addition, there were correlations between sleepiness and postural control variables with opened eyes (r = 0.616, 95% confidence interval [CI] = 0.361–0.815; r = 0.538; 95% CI = 0.280–0.748) and closed eyes (r = 0.557; 95% CI = 0.304–0.764, r = 0497; 95% CI = 0.325–0.715) and a pronounced effect of sleepiness on postural sway (R2 = 0.393; 95% CI = 0.001–0.03). Therefore, 12-h night work system and sleepiness showed a negative impact in postural and psychomotor vigilance performance of night workers. As unexpected, the force platform was feasibility to detect sleepiness in this population, underscoring the possibility of using this method in the workplace to prevent occupational injuries and accidents. 相似文献
107.
108.
Human calumenin (hCALU) is a six EF-hand protein belonging to the CREC family. As other members of the family, it is localized in the secretory pathway and regulates the activity of SERCA2a and of the ryanodine receptor in the endoplasmic reticulum (ER). We have studied the effects of Ca2+ binding to the protein and found it to attain a more compact structure upon ion binding. Circular Dichroism (CD) measurements suggest a major rearrangement of the protein secondary structure, which reversibly switches from disordered at low Ca2+ concentrations to predominantly alpha-helical when Ca2+ is added. SAXS experiments confirm the transition from an unfolded to a compact structure, which matches the structural prediction of a trilobal fold. Overall our experiments suggest that calumenin is a Ca2+ sensor, which folds into a compact structure, capable of interacting with its molecular partners, when Ca2+ concentration within the ER reaches the millimolar range. 相似文献
109.