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The Relationship between melatonin receptor 1A gene (MTNR1A) polymorphism and reproductive performance in Sarda breed sheep
No full textIn several species the circadian changes in melatonin secretion acts as the organic informer of the photoperiodic trend. Some physiological functions, such as reproduction, are influenced by seasonal melatonin secretion. In small ruminants polymorphisms at the MTNR1A gene are associated with non-seasonal breeding. The aim of this research was to evaluate if the MTNR1A gene polymorphism influences first conception, second and third lambing in Sarda breed sheep. Two-hundred ewe lambs, born between 10th November and 10th December 2008, were randomly chosen from four selected farms and genotyped for the A612G polymorphism at the MTNR1A gene. To rule out a possible confounding effect of the low frequency of the A/A genotype in Sarda sheep, 800 ewe lambs were genotyped and 85 individuals were selected for each genotype (A/A, A/G and G/G). Fertile rams were given access to the selected ewe lambs from 30th July to 30th October 2009 during the first year, and from 1st May to 30th October 2010 and 2011 on the second and third year, respectively. Mating and lambing dates were recorded for each ewe during the three years. In the first year ewe lambs showed no differences among genotypes in their fertility rates, litter size and mean number of days from ram introduction to parturition. However, in the second and third year G/G and A/G genotypes showed, a shorter interval (expressed in days) from ram introduction to lambing, compared to A/A genotype (P<0.05). During the second year fertility rate for the G/G, A/G and A/A genotypes, were 91.7%, 90.2% and 89.9%, respectively; whereas in the third year fertility rates were 91.5% for G/G, 91.8% for A/G and 93.0% for A/A genotypes. We speculate that the similarity in fertility rates among different genotypes may be due to a carry-over effect because ew\es carrying different genotypes were not separated. Results indicate that the MTNR1A gene polymorphism does not influence the onset of reproductive activity in Sarda ewe lambs, but this single nucleotide polymorphism (SNP) reveals its influence in the earlier reproductive resumption in the adult ewes. The interval from rams׳ introduction to lambing may be longer if animals with different genotypes were kept separated
Raltegravir-based therapy in a cohort of HIV/HCV co-infected individuals
No full textThe relationship between hepatic tolerance and hepatitis C virus (HCV) co-infection has not been extensively studied in clinical practice. We assessed the efficacy and safety of raltegravir-based therapy in an Italian cohort of HIV/HCV co-infected patients. One hundred and forty patients with HIV/HCV co-infection initiating raltegravir from SCOLTA project (Surveillance Cohort Long-Term Toxicity Antiretrovirals) were examined. Of them, 43 were women, with mean age of 45.4 ± 6.4 years; 65 (46%) had undetectable HIV-RNA < 50 copies/mL and 75 (54%) HIV-RNA ≥ 50 copies/mL. According to CDC classification, 49 (35%) were in stage C. Based on Fib4 score at the time of starting raltegravir, patients were classified in class I in 41 cases, class II in 68 and in class III in 31 cases. Globally, the Fib4 score slightly decreased during 24 months follow-up, from 2.2 to a value of 1.8. Hepatic adverse events of any grade were observed in 67 patients, of which only 2 cases (3%) had severe liver toxicity (grade 3–4). Only one patient had to discontinue the therapy because of adverse events. According to univariate analysis, being in CDC stage C represented a risk for the development of liver toxicity, with a hazard ratio (HR) of 2.27 (95% CI 1.06–4.84, P = 0.033). None of the other variables considered (age, sex, years since detection of HIV and HCV-RNA detectable, years of previous HIV therapy, concomitant therapy with PI or NRTI, CD4+ cell count, Fib4, and transaminases level at baseline) resulted statistically correlated to the outcome. In conclusion, raltegravir-based regimens can be safely used in HCV infected patients; in this study, the hepatic toxicity has been found to be more frequent in patients with an advanced HIV disease (CDC stage C), independently of HIV-RNA suppression at raltegravir initiation
The Immune-related role of BRAF in melanoma
No full textBackground: The existence of a dichotomy between immunologically active and quiescent, tumor phenotypes has been recently recognized in several types of cancer. The activation of a Th1 type of immune signature has been shown to confer better prognosis and likelihood to respond to immunotherapy. However, whether such dichotomy depends on the genetic make-up of individual cancers is not known yet. BRAF and NRAS mutations are commonly acquired during melanoma progression. Here we explored the role of BRAF
and NRAS mutations in influencing the immune phenotype based on a classification previously identified by our group.
Methods: One-hundred-thirteen melanoma metastases underwent microarray analysis and
BRAF and NRAS genotyping. Allele-specific PCR was also performed in order to exclude low-frequency mutations.
Results: Comparison between BRAF and NRAS mutant versus wild type samples identified mostly constituents or regulators of MAPK and related pathways. When testing gene lists discriminative of BRAF, NRAS and MAPK alterations, we found that 112 BRAF-specific transcripts were able to distinguish the two immune-related phenotypes already described in melanoma, with the poor phenotype associated mostly with BRAF mutation. Noteworthy, such association was stronger in samples displaying low BRAF mRNA expression. However, when testing NRAS mutations, we were not able to find the same association.
Conclusion: This study suggests that BRAF mutation-related specific transcripts associate
with a poor phenotype in melanoma and provide a nest for further investigation.</br
Benzotriazole: an overview on its versatile biological behavior
No full textDiscovered in late 1960, azoles are heterocyclic compounds class which constitute the largest group of available antifungal drugs. Particularly, the imidazole ring is the chemical component that confers activity to azoles. Triazoles are obtained by a slight modification of this ring and similar or improved activities as well as less adverse effects are reported for triazole derivatives. Consequently, it is not surprising that benzimidazole/benzotriazole derivatives have been found to be biologically active. Since benzimidazole has been widely investigated, this review is focused on defining the place of benzotriazole derivatives in biomedical research, highlighting their versatile biological properties, the mode of action and Structure Activity Relationship (SAR) studies for a variety of antimicrobial, antiparasitic, and even antitumor, choleretic, cholesterol-lowering agents
Signal transduction in primary human T lymphocytes in altered gravity during parabolic flight and clinostat experiments
No full textBackground/Aims: Several limiting factors for human health and performance in microgravity have been clearly identified arising from the immune system, and substantial research activities are required in order to provide the basic information for appropriate integrated risk management. The gravity-sensitive nature of cells of the immune system renders them an ideal biological model in search for general gravity-sensitive mechanisms and to understand how the architecture and function of human cells is related to the gravitational force and therefore adapted to life on Earth. Methods: We investigated the influence of altered gravity in parabolic flight and 2D clinostat experiments on key proteins of activation and signaling in primary T lymphocytes. We quantified components of the signaling cascade 1.) in non-activated T lymphocytes to assess the “basal status” of the cascade and 2.) in the process of activation to assess the signal transduction. Results: We found a rapid decrease of CD3 and IL-2R surface expression and reduced p-LAT after 20 seconds of altered gravity in non-activated primary T lymphocytes during parabolic flight. Furthermore, we observed decreased CD3 surface expression, reduced ZAP-70 abundance and increased histone H3-acetylation in activated T lymphocytes after 5 minutes of clinorotation and a transient downregulation of CD3 and stable downregulation of IL-2R during 60 minutes of clinorotation. Conclusion: CD3 and IL-2R are downregulated in primary T lymphocytes in altered gravity. We assume that a gravity condition around 1g is required for the expression of key surface receptors and appropriate regulation of signal molecules in T lymphocytes
Analysis of runs of homozygosity and their relationship with inbreeding in five cattle breeds farmed in Italy
No full textIncreased inbreeding is an inevitable consequence of selection in livestock populations. The analysis of high-density single nucleotide polymorphisms (SNPs) facilitates the identification of long and uninterrupted runs of homozygosity (ROH) that can be used to identify chromosomal regions that are identical by descent. In this work, the distribution of ROH of different lengths in five Italian cattle breeds is described. A total of 4095 bulls from five cattle breeds (2093 Italian Holstein, 749 Italian Brown, 364 Piedmontese, 410 Marchigiana and 479 Italian Simmental) were genotyped at 54K SNP loci. ROH were identified and used to estimate molecular inbreeding coefficients (FROH), which were compared with inbreeding coefficients estimated from pedigree information (FPED) and using the genomic relationship matrix (FGRM). The average number of ROH per animal ranged from 54 ± 7.2 in Piedmontese to 94.6 ± 11.6 in Italian Brown. The highest number of short ROH (related to ancient consanguinity) was found in Piedmontese, followed by Simmental. The Italian Brown and Holstein had a higher proportion of longer ROH distributed across the whole genome, revealing recent inbreeding. The FPED were moderately correlated with FROH > 1 Mb (0.662, 0.700 and 0.669 in Italian Brown, Italian Holstein and Italian Simmental respectively) but poorly correlated with FGRM (0.134, 0.128 and 0.448 for Italian Brown, Italian Holstein and Italian Simmental respectively). The inclusion of ROH > 8 Mb in the inbreeding calculation improved the correlation of FROH with FPED and FGRM. ROH are a direct measure of autozygosity at the DNA level and can overcome approximations and errors resulting from incomplete pedigree data. In populations with high linkage disequilibrium (LD) and recent inbreeding (e.g. Italian Holstein and Italian Brown), a medium-density marker panel, such as the one used here, may provide a good estimate of inbreeding. However, in populations with low LD and ancient inbreeding, marker density would have to be increased to identify short ROH that are identical by descent more precisely
Electronic and steric effects in rollover C–H bond activation
No full textSteric and electronic factors in rollover C–H bond activation of substituted 2,2′-bipyridines, mediated by platinum(II), have been investigated by comparing the influence of two substituents, CH3 and CF3, on the progress of the reaction. The substituents were chosen to have similar steric hindrance but different electronic effects and were placed in position 6 (i.e., near one of the nitrogen atoms) or in position 5, which allows, in part, electronic and steric influence to be distinguished. The ligands studied, 6-methyl-2,2′-bipyridine, 5-methyl-2,2′-bipyridine, 6-trifluoromethyl-2,2′-bipyridine, and 5-trifluoromethyl-2,2′-bipyridine, were compared to unsubstituted 2,2′-bipyridine in the reaction with the electron-rich complex [Pt(Me)2(DMSO)2]. The electron-withdrawing CF3 group was found to have a significant effect in accelerating the cyclometalation reaction. The substituent in position 6 influences the stability of the intermediate adduct [Pt(N,N)(Me)2] (N,N = chelated bipyridine), as indicated by density functional theory calculations. The steric hindrance of substituted bipyridines was also evaluated by defining and measuring the angle ζ in [Pt(N,N)(Me)2] adducts. The presence of a substituent in position 6 causes destabilization of the adduct, acceleration of the cyclometalation reaction, and regioselectivity of C–H bond activation
An NMR study on the 6,6′-(2-(diethylamino)ethylazanediyl)bis(methylene)bis(5-hydroxy-2-hydroxymethyl-4H-pyran-4-one) interaction with Al<sup>III</sup> and Zn<sup>II</sup> ions
No full textHere we report about the complex formation among an amine-bearing bis-kojic acid, 6,6′-(2-(diethylamino)ethylazanediyl)bis(methylene)bis(5-hydroxy-2-hydroxymethyl-4H-pyran-4-one) and two metal ions, the trivalent hard and not essential metal ion AlIII and the borderline and essential divalent metal ion ZnII. We carried out a thorough NMR study in order to reach the indispensable structural information on the behavior of these complexes in solution. A combination of 1D, 2D total correlation spectroscopy, heteronuclear single quantum coherence spectroscopy, nuclear Overhauser enhancement spectroscopy and rotating-frame Overhauser effect spectroscopy experiments was used to assign the signals of both free and metal-bound ligand at different pH values. Our results highlighted the different coordination behaviors of the ligand towards the different metal ions, depending on their hard or borderline character. The trivalent metal ion, AlIII, mainly forms dinuclear helicate complexes of M2L3 stoichiometry, and the coordination only involves both hydroxypyrone (O,O)-donor atoms. NMR data are in agreement with the presence of a rigid and symmetric structure of L9–AlIII complexes up to physiological pH. On the contrary, with the divalent metal ion, NMR data showed the coexistence of several species in solution though ZnII forms complexes of ML stoichiometry at physiological pH, where the metal coordination involves the nitrogen atoms of both the linker and the side-chain amine groups together with the oxygen atoms of phenolate groups. The in solution study will be of interest for providing an insight on the ligand bioavailability and on its behavior in the chelation treatments
Sorption of ofloxacin and chrysoidine by grape stalk: a representative case of biomass removal of emerging pollutants from wastewater
No full textEmerging pollutants, as antibiotics or dyes, in aquatic ecosystems are a crucial concern and numerous techniques have been developed for their removal. Efficiency, cost effectiveness, and biodegradability reveal biomass sorption as one of the most appealing methods. This study aims to evaluate the effectiveness of grape stalk as a sorbent for ofloxacin (a fluoroquinolone antibiotic) and chrysoidine (an azo-dye). The kinetic and the thermodynamic aspects of the sorption were studied. A pseudo first-order kinetic behavior is shown by both substances, though the kinetic constants of ofloxacin are almost double than those of chrysoidine. The sorption isotherms, which strictly follow the Langmuir model, show remarkable differences as a function of pH and of biomass size. The trend of Langmuir parameters, Qmax and K, as a function of pH and size, is discussed, and different binding mechanisms are proposed. Kinetic and thermodynamic parameters prefigure grape stalk as a potential biomass for scavenging toxic substances from wastewater
Making it easier the identification of vascular plants in Mediterranean temporary ponds: the online interactive guide
No full textThe aims of our research were: i) to implement a checklist of vascular plants, and ii) to create an interactive guide for the identification of plants growing in the Mediterranean temporary ponds of Sardinia