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101.
Carrai M Steinke V Vodicka P Pardini B Rahner N Holinski-Feder E Morak M Schackert HK Görgens H Stemmler S Betz B Kloor M Engel C Büttner R Naccarati A Vodickova L Novotny J Stein A Hemminki K Propping P Försti A Canzian F Barale R Campa D 《PloS one》2011,6(6):e20464
Molecular sensing in the lingual mucosa and in the gastro-intestinal tract play a role in the detection of ingested harmful drugs and toxins. Therefore, genetic polymorphisms affecting the capability of initiating these responses may be critical for the subsequent efficiency of avoiding and/or eliminating possible threats to the organism. By using a tagging approach in the region of Taste Receptor 2R38 (TAS2R38) gene, we investigated all the common genetic variation of this gene region in relation to colorectal cancer risk with a case-control study in a German population (709 controls and 602 cases) and in a Czech population (623 controls and 601 cases). We found that there were no significant associations between individual SNPs of the TAS2R38 gene and colorectal cancer in the Czech or in the German population, nor in the joint analysis. However, when we analyzed the diplotypes and the phenotypes we found that the non-taster group had an increased risk of colorectal cancer in comparison to the taster group. This association was borderline significant in the Czech population, (OR = 1.28, 95% CI 0.99–1.67; Pvalue = 0.058) and statistically significant in the German population (OR = 1.36, 95% CI 1.06–1.75; Pvalue = 0.016) and in the joint analysis (OR = 1.34, 95% CI 1.12–1.61; Pvalue = 0.001). In conclusion, we found a suggestive association between the human bitter tasting phenotype and the risk of CRC in two different populations of Caucasian origin. 相似文献
102.
Zainab Saad Yusuf Tugba Kevser Uysal Ender Simsek Alessio Nocentini Sameh Mohamed Osman Claudiu T. Supuran
zen
zensoy Güler 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):1340
Carbonic anhydrases (EC 4.2.1.1) catalyse the reversible hydration of CO2 into bicarbonate and protons. As a hypoxia-sensitive and tumour-associated isoform, isoform CA IX, is significantly overexpressed in various malignancies, being a validated target for new anticancer/antimetastatic drugs. A multitude of studies has shown that CA IX inhibition decreases cancer cell proliferation and metastasis through pHe/pHi modulation and enhancement of ferroptosis among others. Numerous studies demonstrated increased efficacy of cytotoxic drugs combined with CA inhibitors (CAIs) in various cancer types. We tested the inhibitory effect of boric acid (BA), an inorganic Lewis acid, on CA IX as well as other isoforms (CA I, II, and XII). BA acted as a millimolar in vitro CAI, decreased proliferation of two cancer cell lines, although not strong correlations between the in vitro inhibition and in vivo effects were observed. The mechanism of antiproliferative action of BA should be investigated in more detail. 相似文献
103.
Gambarino S Costa C Astegiano S Piasentin EA Segoloni GP Cavallo R Bergallo M 《Molecular biotechnology》2011,49(2):151-158
Polyomavirus BK latently persist in different sites, including the renourinary tract, and may reactivate causing nephropathy
in renal transplant recipients or hemorrhagic cystitis in bone marrow recipients. Based on the sequence of the VP1 gene, four
genotypes have been described, corresponding to the four serologically differentiated subtypes I–IV, with different prevalence
and geographic distribution. In this study, the development and clinical validation of four different Real-Time PCR assays
for the detection and discrimination of BKV genotypes as a substitute of DNA sequencing are described. 379 BK VP1 sequences,
belonging to the main four genotypes, were aligned and “hot spots” of mutation specific for all the strains or isolates were
identified. Specific primers and probes for the detection and discrimination of each genotype by four Real-Time PCR assays
were designed and technically validated. Subsequently, the four Real-Time PCR assays were used to test 20 BK-positive urine
specimens from renal transplant patients, and evidenced a prevalence of BK genotype I, as previously reported in Europe. Results
were confirmed by sequencing. The availability of a rapid and simple genotyping method could be useful for the evaluation
of BK genotypes prevalence and studies on the impact of the infecting genotype on viral biological behavior, pathogenic role,
and immune evasion strategies. 相似文献
104.
105.
Likelihood of changes in forest species suitability,distribution, and diversity under future climate: The case of Southern Europe 下载免费PDF全文
Forest conservation strategies and plans can be unsuccessful if the new habitat conditions determined by climate change are not considered. Our work aims at investigating the likelihood of future suitability, distribution and diversity for some common European forest species under the projected changes in climate, focusing on Southern Europe. We combine an Ensemble Platform for Species Distribution Models (SDMs) to five Global Circulation Models (GCMs) driven by two Representative Concentration Pathways (RCPs), to produce maps of future climate‐driven habitat suitability for ten categories of forest species and two time horizons. For each forest category and time horizon, ten maps of future distribution (5 GCMs by 2 RCPs) are thus combined in a single suitability map supplied with information about the “likelihood” adopting the IPCC terminology based on consensus among projections. Then, the statistical significance of spatially aggregated changes in forest composition at local and regional level is analyzed. Finally, we discuss the importance, among SDMs, that environmental predictors seem to have in influencing forest distribution. Future impacts of climate change appear to be diversified across forest categories. A strong change in forest regional distribution and local diversity is projected to take place, as some forest categories will find more suitable conditions in previously unsuitable locations, while for other categories the same new conditions will become less suited. A decrease in species diversity is projected in most of the area, with Alpine region showing the potentiality to become a refuge for species migration. 相似文献
106.
107.
Ascenzi P Bocedi A Fasano M Gioia M Marini S Coletta M 《Journal of inorganic biochemistry》2005,99(5):1255-1259
The effect of pH on the X-band electron paramagnetic resonance (EPR) spectrum of ferrous nitrosylated human adult tetrameric hemoglobin (HbNO) as well as of ferrous nitrosylated monomeric alpha- and beta-chains has been investigated, at -163 degrees C. At pH 7.3, the X-band EPR spectrum of tetrameric HbNO and ferrous nitrosylated monomeric alpha- and beta-chains displays a rhombic shape. Lowering the pH from 7.3 to 3.0, tetrameric HbNO and ferrous nitrosylated monomeric alpha- and beta-chains undergo a transition towards a species characterized by a X-band EPR spectrum with a three-line splitting centered at 334mT. These pH-dependent spectroscopic changes may be taken as indicative of the cleavage, or the severe weakening, of the proximal HisF8-Fe bond. In tetrameric HbNO, the pH-dependent spectroscopic changes depend on the acid-base equilibrium of two apparent ionizing groups with pK(a) values of 5.8 and 3.8. By contrast, the pH-dependent spectroscopic changes occurring in ferrous nitrosylated monomeric alpha- and beta-chains depend on the acid-base equilibrium of one apparent ionizing group with pK(a) values of 4.8 and 4.7, respectively. The different pK(a) values for the proton-linked spectroscopic transition(s) of tetrameric HbNO and ferrous nitrosylated monomeric alpha- and beta-chains suggest that the quaternary assembly drastically affects the strength of the proximal HisF8-Fe bond in both subunits. This probably reflects a 'quaternary effect', i.e., structural changes in both subunits upon tetrameric assembly, which is associated to a relevant variation of functional properties (i.e., proton affinity). 相似文献
108.
Milani M Pesce A Nardini M Ouellet H Ouellet Y Dewilde S Bocedi A Ascenzi P Guertin M Moens L Friedman JM Wittenberg JB Bolognesi M 《Journal of inorganic biochemistry》2005,99(1):97-109
Truncated hemoglobins (trHbs) are low-molecular-weight oxygen-binding heme-proteins distributed in eubacteria, cyanobacteria, unicellular eukaryotes, and in higher plants, constituting a distinct group within the hemoglobin (Hb) superfamily. TrHbs display amino acid sequences 20-40 residues shorter than classical (non)vertebrate Hbs and myoglobins, to which they are scarcely related by sequence similarity. The trHb tertiary structure is based on a 2-on-2 alpha-helical sandwich, which represents a striking editing of the highly conserved 3-on-3 alpha-helical globin fold, achieved through deletion/truncation of alpha-helices and specific residue substitutions. Despite their 'minimal' polypeptide chain span, trHbs display an inner tunnel/cavity system held to support ligand diffusion to/from the heme distal pocket, accumulation of heme ligands within the protein matrix, and/or multiligand reactions. Moreover, trHbs bind and effectively stabilize the heme and recognize diatomic ligands (i.e., O2, CO, NO, and cyanide), albeit with varying thermodynamic and kinetic parameters. Here, structural bases for heme binding and diatomic ligand recognition by trHbs are reviewed. 相似文献
109.
110.
Tricker PJ Trewin H Kull O Clarkson GJ Eensalu E Tallis MJ Colella A Doncaster CP Sabatti M Taylor G 《Oecologia》2005,143(4):652-660
Using a free-air CO2 enrichment (FACE) experiment, poplar trees (Populus × euramericana clone I214) were exposed to either ambient or elevated [CO2] from planting, for a 5-year period during canopy development, closure, coppice and re-growth. In each year, measurements
were taken of stomatal density (SD, number mm−2) and stomatal index (SI, the proportion of epidermal cells forming stomata). In year 5, measurements were also taken of leaf
stomatal conductance (g
s, μmol m−2 s−1), photosynthetic CO2 fixation (A, mmol m−2 s−1), instantaneous water-use efficiency (A/E) and the ratio of intercellular to atmospheric CO2 (Ci:Ca). Elevated [CO2] caused reductions in SI in the first year, and in SD in the first 2 years, when the canopy was largely open. In following
years, when the canopy had closed, elevated [CO2] had no detectable effects on stomatal numbers or index. In contrast, even after 5 years of exposure to elevated [CO2], g
s was reduced, A/E was stimulated, and Ci:Ca was reduced relative to ambient [CO2]. These outcomes from the long-term realistic field conditions of this forest FACE experiment suggest that stomatal numbers
(SD and SI) had no role in determining the improved instantaneous leaf-level efficiency of water use under elevated [CO2]. We propose that altered cuticular development during canopy closure may partially explain the changing response of stomata
to elevated [CO2], although the mechanism for this remains obscure. 相似文献