The important role of the central intermediary metabolite acetyl-coenzyme A (AcCoA)for several anabolic and catabolic pathways is well characterised. However, the role of AcCoA as the only known donor of acetyl groups for protein acetylation in regulation of enzyme activities, protein complex stability as well as epigenetic status off chromatin, is only recently emerging. Among multiple other pathways, the autophagy pathway has now been shown to be directly regulated by protein acetylation and deacetylation. Therefore, it was reasoned that the availability of AcCoA, via the modulation of AcCoA generating enzymes, may regulate autophagy. This study has focussed on the role of the acetate-mediated route to nuclear-cytosolic AcCoA synthesis, catalysed by AcCoA synthetase 2 (ACSS2), in the regulation of autophagy.

Para quantificar o teor de lignina em alguns cultivares de aveia, foi utilizado o método espectrofotométrico "lignina solúvel em brometo de acetila – LSBA", onde a lignina é solubilizada em uma solução a 25% de brometo de acetila em ácido acético glacial e em seguida sua absorbância lida a 280 nm; como padrão de referência foi utilizada a lignina extraída da aveia através de uma solução ácida de dioxana. A quantificação da lignina foi realizada em oito cultivares de aveia, nas frações planta inteira, caule e folha, em três estádios de maturidade (45, 55 e 65 dias de idade). Os resultados obtidos foram comparados com três métodos gravimétricos: lignina detergente ácido (LDA), lignina permanganato de potássio (LPer) e lignina Klason (LK). Os quatro métodos estudados mostraram teores de lignina diferentes entre si. Os resultados de LSBA foram superiores para quase todos os cultivares, ocorrendo o inverso para a LDA. Houve uma pequena diferença em relação aos dias de corte, com dados superiores para LSBA, onde o caule apresentou maior variação em relação às demais frações. As curvas de regressão e os espectrogramas indicaram presença de diferenças qualitativas entre as ligninas provenientes da aveia forrageira nos diferentes estádios de maturidade. / To quantify lignin content in some varieties of oat, it was employed the spectrophotometric method acetyl bromide soluble lignin – ABSL where lignin is dissolved into a 25% acetyl bromide solution in glacial acetic acid and its absorbance read at 280 nm; as a standard it was employed a, lignin extracted by mild acidic dioxane solution from the same sample. Lignin quantification was evaluated in eight oat cultivars, divided in three vegetable parts (whole plant, stem and leaf), and three different maturity stages (cuts at 45, 55 and 65 days). Obtained results were compared with three gravimetric methods: acid detergent lignin (ADL), potassium permanganate lignin (PerL) and Klason lignin (KL). All four methodologies yielded different results. Overall, ABSL yielded highest values whereas ADL yielded the lowest ones. There was a slight difference related to maturity, with higher values for ABSL, where stem fraction showed higher variation when comparing to the two other vegetable parts. Regression equations and espectrograms indicated the presence of qualitative differences between lignins from at distinct maturity stages.

This research focuses on diterpenoids from Taiwanese soft corals Xenia umbellata Lamarck, Junceella juncea Pallas and Junceella fragilis Ridley. Twelve diterpenoids in addition to one sesequiterpenoid were isolated. Our investigation of the soft coral X. umbellata Lamarck afforded five natural products, including two new xenicane diterpenes, xenibelatols A-B (1-2), together with two known xenicane diterpenes, 7,8-oxido- isoxeniolide (3), 9-hydroxyxeniolide-F (4), and a cadinene sesequiterpene, xenitorin A (5). Chemical investigation of the gorgonian J. juncea Pallas, has resulted in isolation of a new briarane diterpene, juncenolide H (6). Continuing our investigation of the gorgonian J. fragilis Ridley, we isolated seven briarane diterpenes, including four new briaranes, flajunolides A-D (7-10), along with three known briaranes, junceellolide E (11), umbraculolide A (12), 11This research focuses on diterpenoids from Taiwanese soft corals Xenia umbellata Lamarck, Junceella juncea Pallas and Junceella fragilis Ridley. Twelve diterpenoids in addition to one sesequiterpenoid were isolated. Our investigation of the soft coral X. umbellata Lamarck afforded five natural products, including two new xenicane diterpenes, xenibelatols A-B (1-2), together with two known xenicane diterpenes, 7,8-oxido- isoxeniolide (3), 9-hydroxyxeniolide-F (4), and a cadinene sesequiterpene, xenitorin A (5). Chemical investigation of the gorgonian J. juncea Pallas, has resulted in isolation of a new briarane diterpene, juncenolide H (6). Continuing our investigation of the gorgonian J. fragilis Ridley, we isolated seven briarane diterpenes, including four new briaranes, flajunolides A-D (7-10), along with three known briaranes, junceellolide E (11), umbraculolide A (12),11£\, 20£\-epoxy-4-deacetoxy junceellolide D (13). The new compounds 1,2 and 6-10 possess xenicane-type and briarane-type skeletons respectively. The structures of new compounds were determined by 1D-, 2D-NMR spectroscopic analysis and physical methods such as optical rotation, UV, IR, mass spectrum, as well as comparison with the spectroscopic data reported for related compounds. Compounds 1 and 2 are geometric isomers of compounds 3 and 4. The only difference between them resides in the side chain. The geometry of the side chain influenced the relative spatial proximity of H-12, H-13, H-14 to the carbonyl at C-3, and consequently the extent to which these protons are subjected to the anisotropic effects of the carbonyl. Compounds 6-10 have acetyl groups at C-2, C-9, C-12, C-14 positions. Because of structural difference appears in briarane skeleton, they showed different chemical shifts in specific positions. Biological activity test¡Arevealed that compound 5 exhibited moderate cytotoxic activity against KB and WiDr cancer cell lines with ED50 values at 5.9 and 9.9 £gg/ml respectively.

Breast cancer is the most frequent malignancy among women, especially in Western societies. Highly penetrant genes such as BRCA1 and BRCA2, together with the reproductive history can constitute only 30% of the cause, so there should be other common genes, which may play a role in breast carcinogenesis according to one&#039 / s lifestyle. In our case, the effect of N-acetyl transferases (NAT1, NAT2) and glutathione-S transferases (GSTM1&amp / GSTT1) were investigated, since variations in these genes may alter their enzymatic activity and therefore their capacity to biotransform xenobiotic compounds. To evaluate the potential association between NAT1, NAT2, GSTM1 and GSTT1 genotypes and development of breast cancer, a hospital based case-control study was conducted in a Turkish study population consisting of 37 histologically confirmed incident breast cancer cases and 34 control subjects with no present or previous history of cancer. The only recognizable difference between case and control groups is the percentage of GSTM1 deletion, 67.6% and 44.1% respectively (p=0.047). The frequency of rapid NAT2 acetylator genotype is 44.4% in cases and 23.5% in controls. Especially, women with NAT2 rapid acetylator and GSTM1 null genotypes were at the elevated risk (OR, 3.8 / CI, 0.9-15.4). NAT1 rapid acetylator genotype showed no association with breast cancer. These results suggest that GSTM1 null genotype is a susceptibility factor for breast cancer, particularly in the presence of NAT2 rapid acetylator genotype.

No description available.

Darbo tikslas: susintetinti naujus antibakterinius ir priešgrybelinius 5-ariliden-4-tiazolidinon-N-aminorūgščių (leucino, triptofano) ir naujus 2-acetil-1-naftolio junginius ir prijungtų pakaitų įtaką junginių priešmikrobiniam aktyvumui. Uždaviniai: 1. Apžvelgti esamą literatūrą apie bakterijų ir grybelių sukeliamas infekcijas, kovos prieš infekcijas metodus, strategijas. 2. Optimizuoti naujų galimų vaistų struktūrų paieškas pasitelkiant kompiuterinio modeliavimo programą ,,SYBYL-X“ ir junginių biologinio aktyvumo prognozavimo programą ,,PASSonline“. 3. Susintezuoti naujus 5-ariliden-4-tiazolidinon-N-aminorūgščių (leucino, triptofano) ir naujus 2-acetil-1-naftolio junginius. 4. Atlikti junginių charakteristikų analizę, pasitelkiant junginių plonasluoksnės chromatogafijos, lydimosi temperatūrų, ESC, UV, IR spektrų metodus. 5. Nustatyti susintezuotų junginių mikrobiologinį aktyvumą prieš Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, Bacillus subtillis, Bacillus cereus, Candida albicans. Tyrimo metodai: junginių priešmikrobinis aktyvumas buvo prognozuojamas naudojant PASSonline ir kompiuterinio molekulių modeliavimo programą SYBYL-X 1.1. Antimikrobinis aktyvumas buvo tiriamas ,,in vitro” atmetimo būdu, ,,užnuodytos lėkštelės metodu“ bakterijas užnešant ant junginio tirpalo suspenduoto Miulerio-Hintono agare. Tyrimo rezultatai: Gauti plačiausią aktyvumo spektrą... [toliau žr. visą tekstą] / The goal: to synthesize new antibacterial and antifungal 5-aryliden-4-thiazolidinone-N-amino acids (leucine, tryptophan) and a new 2-acetyl-1-naphthol compounds and associated substitutions influence on compounds for anti-microbial activity. Objectives: 1. Review the existing literature on bacterial and fungal infections, anti-infection techniques, strategies. 2. Optimize new structures of potential drug searches through computer simulation program, Sybyl - X compounds and biological activity prediction program, PASSonline. 3. Synthesise new 5 - ariliden - thiazolidine - 4 -N - amino acids (leucine, tryptophan) and a new 2-acetyl-1-naphthol compounds. 4. Perform an analysis of the characteristics of compounds using thin layer chromatography, melting temperatures, HPLC, UV, IR spectra methods. 5. Set synthesised compounds of microbial activity against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, Bacillus subtillis, Bacillus cereus, Candida albicans. Research methods: antimicrobial activity of the compounds were predicted using “PASSonline” and computer molecular modeling program “Sybyl -X 1.1”. Antimicrobial activity was studied “in vitro” rejection method as “poisoned dish method”- bacteria applied on the solution suspending in a Muller - Hinton agar. The results: Synthesised compounds having the widest spectrum of activity with two... [to full text]

Thesis (Ph. D.)--West Virginia University, 2006. / Title from document title page. Document formatted into pages; contains ix, 175 p. : ill. Includes abstract. Includes bibliographical references.

Master of Science / Biochemistry and Molecular Biophysics Interdepartmental Program / Timothy P. Durrett / Many Euonymus species express an acetyltransferase enzyme in their seeds which catalyzes the transfer of an acetyl group from acetyl-CoA to the sn-3 position of diacylglycerol (DAG) producing unusual acetyl-1,2-diacyl-sn-glycerols (acetyl-TAG). The presence of the sn-3 acetate group gives acetyl-TAG with unique physical properties over regular triacylglycerol (TAG) found in vegetable oils. The useful characteristics of acetyl-TAG oil offer advantages for its use as emulsifiers, lubricants, and 'drop-in' biofuels. One enzyme, Euonymus alatus diacylglycerol acetyltransferase (EaDAcT), responsible for acetyl-TAG synthesis in nature was previously isolated from the seeds of Euonymus alatus (burning bush) and expressed in the oilseed crop Camelina sativa. Expression of EaDAcT successfully led to production of high levels of acetyl-TAG in camelina seeds. To further increase acetyl-TAG accumulation in transgenic camelina seeds, multiple strategies were examined in this study. Expression of a new acetyltransferase enzyme (EfDAcT) isolated from the seeds of Euonymus fortunei, which was previously shown to possess higher in vitro activity and in vivo acetyl-TAG levels compared to EaDAcT, increased acetyl-TAG accumulation by 20 mol%. Suppression of the endogenous competing enzyme DGAT1 further enhanced acetyl-TAG accumulation to 90 mol% in selected transgenic line. Studying the regulation of EfDAcT transcript, protein, and acetyl-TAG levels during seed development further provided new insights on the factors limiting acetyl-TAG accumulation.

Polysialic acid (PSA) is a developmentally regulated glycan made of repeating sialic acid monomers with α2-8 linkages. PSA has very limited expression in adults, and modifies only a few cell-surface proteins. However, PSA is overexpressed in several human cancers and is associated with metastasis and poor prognosis. We have described a derivative of PSA containing a mixture of de-N-acetyl and N-acetyl neuraminic acid residues (dPSA) found intracellularly in many normal human tissues but expressed at much higher levels on the cell surface of many human cancer cell lines. The proteins modified with dPSA and dPSA function in normal and abnormal human biology are unknown. The purpose of this study was to identify protein(s) modified with PSA and possible dPSA-dependent functions in cancer cell lines that express dPSA antigens. Using co-immunoprecipitation with the anti-dPSA monoclonal antibody SEAM 2 and mass spectroscopy, we identified membrane-associated nucleolin that is either directly modified or associated with dPSA. In addition, knocking down expression of the polysialyltransferase ST8SiaII (STX) in SK-MEL-28 human melanoma cells nearly eliminated dPSA and nucleolin from membranes but had no effect on the levels of nuclear nucleolin, and resulted in aberrant cell morphology, cell adhesion, and motility. The data suggest that cell-surface nucleolin depends on modification with dPSA, and that dPSA-modified nucleolin has an important role in cell adhesion and migration.

O desempenho animal pode ser melhorado pelo incremento na digestibilidade dos alimentos. Um dos elementos neste processo é a acurada caracterização da composição química. Objetivando avaliar quatro métodos para determinar o teor de lignina, foram estudadas cinco gramíneas: Brachiaria brizantha cv. Marandú, Brachiaria brizantha cv. Xaraés (MG-5), Panicum maximum cv. Mombaça, Pennisetum purpureum cv. Cameroon e Pennisetum purpureum cv. Napier. As frações fibrosas da parede celular (PC), fibra em detergente neutro (FDN) e fibra em detergente ácido (FDA) aumentaram conforme as plantas amadureceram, refletindo as mudanças na composição dos componentes da parede celular (celulose, hemicelulose e lignina). Os valores de PC foram superiores aos da FDN indicando solubilização da pectina e outros oligossacarídeos da parede celular na solução de detergente neutro. O método LDA apresentou os menores teores de lignina, evidenciando a solubilização de parte da lignina na solução de detergente ácido. Os resultados de LPer foram maiores que os de LDA, que pode ser devido à oxidação da celulose e pectina pelo permanganato de potássio. Os teores de LK foram maiores que os de LDA possivelmente por contaminação protéica, mas, menores que os de LPer. Os teores de LBA foram maiores que os outros três métodos. A digestibilidade acompanhou, de forma inversa, o estádio de maturidade das plantas. A digestibilidade in vitro apresentou forte correlação negativa com os teores de lignina para todos os métodos, menos para LPer. Encontrou-se um valor de relação de 2,23, entre os métodos LDA e LBA, que, ao ser aplicado, nos teores de LDA, resultou em reta similar ao da LBA. Chama a atenção como este valor de 2,23 é muito próximo ao 2,4 utilizado nas equações B2 e C das frações de carboidratos do \"Cornell Net Carbohydrate & Protein System\" e nas equações do National Research Counsil de 1996, para corrigir o teor de lignina. O método LBA é um método fácil e conveniente para determinar a concentração de lignina em forrageiras e uma boa opção para uso rotineiro nas análises de laboratório. / Animal performance can be improved by enhancing feed digestibility. One of the elements for this process is an accurate characterization of feedstuff chemical composition. With the objective of evaluating four methods used today for lignin determination, five grasses were used: Brachiaria brizantha cv. Marandú, Brachiaria brizantha cv. Xaraés (MG-5), Panicum maximum cv. Mombaça, Pennisetum purpureum cv. Cameroon e Pennisetum purpureum cv. Napier, All fibrous fractions, neutral detergent fiber (NDF), acid detergent fiber (ADF) and cell wall (CW), increased as the plants matured, reflecting the changes in the CW composition (cellulose, hemicellulose and lignin). The values obtained for CW were higher than those obtained for NDF, indicating solubilization of pectin and other cell wall oligosaccharides in the neutral detergent solution. The ADL method produced the lowest lignin values, reflecting lignin solubilization by the acid detergent solution. PerL results were higher than those of ADL, possibly due to hemicellulose and pectin oxidation by potassium permanganate. The values for KL were higher than those of ADL, possibly due to protein contamination, but were lower than PerL values. ABL values were the highest among all methods. Digestibility inversely followed plant maturity throughout the study. In vitro dry matter digestibility showed high negative correlation with lignin contents. A 2,23 ratio between ADL and ABL methods was found, which when applied to ADL values, resulted in a curve similar to ABL method curve. It is interesting to note that, this value of 2,23 is very close to the 2,4 used in carbohydrate fractions B2 and C of the \"Cornell Net Carbohydrate & Protein System\", for the correction of lignin content. The ABL method is easy and convenient for total lignin content determination in forages.