The synthesis of a novel fused nitrogen heterocycle, benzoquinolone, for evaluation as a photocleavable protecting group is described for the first time by coupling to model amino acids (alanine, ...phenylalanine and glutamic acid). Conversion of the phenylalanine ester conjugate to the thionated derivative was accomplished by reaction with Lawesson’s reagent. Photocleavage studies of the carbonyl and thiocarbonyl benzoquinolone conjugates in various solvents and at different wavelengths (300, 350 and 419 nm) showed that the most interesting result was obtained at 419 nm for the thioconjugate, revealing that the presence of the thiocarbonyl group clearly improved the photolysis rates, giving practicable irradiations times for the release of the amino acids (less than 1 min).
Model amino acid ester conjugates bearing heterocycles with a thiocarbonyl group (thiocoumarins and thioquinolones) were prepared by a thionation reaction of the corresponding carbonyl precursors, ...with the aim of obtaining conjugates with higher photosensitivity at longer wavelengths. Photolysis studies were carried out under irradiation at different wavelengths in a photochemical reactor (250, 300, 350 and 419nm), and it was found that the ester bond between the heterocycle and the model amino acid in the thionated analogues cleaved readily with shorter irradiation times than those of the corresponding precursors. Moreover, fast photolysis at 419nm for thioquinolone ester conjugates (within minutes) was particularly interesting and the fact that some of the reported heterocycles displayed very different irradiation times, may provide the possibility for selective removal of one group in the presence of another photocleavable group. The (quinolin-2-thione-4-yl) methyl group may be considered as a new and very effective addition to the family of photocleavable protecting groups for carboxylic acids.
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In order to evaluate the application of quinolone as a new photocleavable protecting group, in comparison with coumarin, a series of model phenylalanine conjugates were prepared by reaction with ...chloromethylated O and N heterocycles. The photophysical properties of the resulting ester conjugates were evaluated as well as the photosensitivity under irradiation at 250, 300, 350, and 419 nm. The results obtained showed that the quinolone conjugates were readily photolysed, with complete release of the amino acid in short irradiation times and could be considered a new addition to the family of photocleavable protecting groups for the carboxylic acid function of amino acids.
A novel fluorescent amino acid, L-4-chloromethylcoumarin-6-yl-alanine, was obtained from tyrosine by a Pechmann reaction. The assembly of the heterocyclic ring at the tyrosine side chain could be ...achieved before or after incorporation of tyrosine into a dipeptide, and amino acid and dipeptide ester conjugates were obtained by coupling to a model N-protected alanine. The behaviour of one of the fluorescent conjugates towards irradiation was studied in a photochemical reactor at different wavelengths (254, 300, 350 and 419 nm). The photoreaction course in methanol/HEPES buffer solution (80:20) was followed by HPLC/UV monitoring. It was found that the novel unnatural amino acid could act as a fluorescent label, due to its fluorescence properties, and, more importantly, as a photoactivable unit, due to the short irradiation times necessary to cleave the ester bond between the model amino acid and the coumarin-6-yl-alanine.
The synthesis of several phenacyl ester derivatives linked to oxygen and nitrogen heterocycles, benzoquinolone and (benzo)coumarins, was carried out in an effort to obtain systems that could be ...applied as photocleavable (bi)functional linkers for solid phase peptide synthesis. The heterocycles were attached to a spacer, with different lengths, followed by coupling to 2-bromo-1-phenylpropan-1-one, acting as a model for the solid support. Photolysis studies of the resulting phenacyl ester derivatives were carried out by irradiation in a photochemical reactor at different wavelengths (300, 350 and 419nm), in methanol/HEPES buffer solution (80:20).
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Sustained virologic response (SVR) in chronic hepatitis C (CHC) treatment denotes that the host genetics controls the immune response and unequivocally contribute to viral clearance or disease ...severity. In this context, single nucleotide polymorphisms (SNPs) in the locus of interferon lambda 3 and 4 genes (
) have been important genetic markers of responsiveness to CHC as prognostic markers for the pegylated-Interferon-alpha/ribavirin (Peg-IFN-α/RBV). Here, we analyzed 12 SNPs at the
region in 740 treatment-naïve patients with CHC infected with hepatitis C virus (HCV) genotypes 1, 2, or 3 treated with Peg-IFN-α/RBV. Individually, rs12979860-CC, rs8109886-CC, or rs8099917-TT were predictive markers of SVR, while rs12979860-CC demonstrated the stronger effect. Besides, the genotypic combination of these three predictors' genotypes, CC/CC/TT, increased the rate of SVR. Serum levels of cytokines and gene expression analysis on the genes
,
,
, and some of the IFN-stimulated genes (ISGs) were measured in a subgroup of 24 treated patients and 24 healthy volunteers. An antagonist effect was highlighted between the expression of
and
mRNA among patients. Besides, a prominent production of the pro-inflammatory chemokines CCL4 and CXCL10 was observed at a 12-week treatment follow-up. Lower serum levels of these chemokines were detected in patients with an rs12979860-CC genotype associated with the better treatment outcome. Also, lower expression levels of the
,
,
genes were observed among rs12979860-CC individuals. In conclusion, a combination of the genotypes at the
locus can act as a better marker for the prognosis for virological responses in an admixed Brazilian population presenting the modulating effect over innate immunity and inflammation that are controlling the outcome of the viral infection, but also other infectious diseases. This study is registered on the ClinicalTrials.gov platform (accession number NCT01889849 and NCT01623336).
We used a high‐precision weighing system and flow‐through respirometry to quantify cutaneous evaporative water loss rates in woolly sheep (wool thickness, ca. 6.5 cm) and haired goats (coat ...thickness, ca. 2.5 cm), while simultaneously recording parallel data obtained from (1) a flow‐through ventilated capsule, (2) a closed hand‐held electronic evaporimeter chamber, and (3) a closed colorimetric paper disc chamber. In comparison to the weighing system and respirometry, used here as a “gold standard” measure of cutaneous evaporative water loss rate, we found relatively good agreement with data obtained from the flow‐through ventilated capsules. However, we found poor agreement with data obtained from the closed electronic evaporimeter chambers (underestimated by 60%, on average) and the closed colorimetric paper disc chambers (overestimated by 52%, on average). This deviation was likely associated with a requirement for shaved skin in the closed chamber methods. Our results therefore cast doubt on the validity of the closed chamber methods for measurement of cutaneous evaporative water loss rates in furred and fleeced mammals, and instead show that more accurate values can be obtained using flow‐through ventilated capsules.
Highlights
Flow‐through ventilated capsules are more accurate than closed chamber methods for measuring cutaneous evaporative water loss rate in furred and fleeced mammals.
The requirement for shaved skin may explain the apparent inaccuracy of the closed chamber methods
Cutaneous evaporative water loss rate obtained with four methods for sheep and goats.
The European university landscape Daraio, Cinzia; Bonaccorsi, Andrea; Geuna, Aldo ...
Research policy,
02/2011, Letnik:
40, Številka:
1
Journal Article
Recenzirano
Odprti dostop
"This paper provides a new and systematic characterization of 488 universities, from 11 European countries: Finland, France, Germany, Hungary, Italy, Netherlands, Norway, Portugal, Spain, Switzerland ...and UK. Using micro indicators built on the integrated Aquameth database, we characterize the European university landscape according to the following dimensions: history/foundation of university, dynamics of growth, specialization pattern, subject mix, funding composition, offer profile and productivity" Die Untersuchung enthält quantitative Daten. Forschungsmethode: empirisch-quantitativ; empirisch; Querschnitt. Die Untersuchung bezieht sich auf den Zeitraum 2004 bis 2007. (Text excerpt, IAB-Doku).
Training sheep for indirect calorimetry trials Fonsêca, Vinícius F.C.; Saraiva, Edilson P.; Maia, Alex S.C. ...
Small ruminant research,
August 2019, 2019-08-00, Letnik:
177
Journal Article
Recenzirano
•We describe the training process for sheep to be assessed in subsequent indirect calorimetry trials.•The restraint and use of facial mask didn’t alter the pattern of respiratory rate of ewes.•At the ...end of training, all animals voluntarily accessed the squeeze chute.•We were able to detect less fearful ewes by examining the inter-individual behavioral responses.
Training methods for animals are useful in experimental work, particularly for respirometry studies. Here we describe the training process for a hair coat sheep breed to be assessed in subsequent indirect calorimetry trials. Behavioral and physiological measurements were taken to determine if the training reduced the animals’ fear reactions, mainly to restraint at the squeeze chute and use of a facial mask. Sixteen Morada Nova sheep with body mass of 32.6 ± 1.8 kg and 2.8 ± 0.9 years of age (±SD) were randomly chosen to undergo the training. The training was divided into three periods across 76 days that consisted of a gradual alteration of the environmental conditions required for the future indirect calorimetry tests. Results revealed that the training had positive or neutral effects on the ewes’ physiological and behavioral performance. At the end of training we observed that the restraint and use of a facial mask did not change (P > 0.05) the respiratory rate of the ewes. Furthermore, all animals voluntarily accessed (P < 0.05) the squeeze chute, and the number of vocalizations and head shakes (P < 0.05) decreased across the training time. Temperament assessments also showed that the group of trained ewes perceived restraint and human presence as a less stressful (P < 0.05) situation than did those that had never experienced the training (i.e., naïve ewes). We were able to detect less fearful ewes by examining the inter-individual behavioral responses using Principal Component analysis, and use them in subsequent calorimetry trials. Our results showed that the resting metabolic rate of similar-sized ewes differenced by less than 10%. In conclusion, this study described a training protocol that was able to habituate sheep to voluntarily access a squeeze chute and use a facial mask for up fifty minutes without apparent changes in behavioral or physiological responses.
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