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Multi-tissue metabolomic analysis of responses to graded calorie restrictionGreen, Cara January 2017 (has links)
With ageing comes a deterioration of metabolic and physiological changes that often manifest themselves as age-related comorbidities. Calorie restriction (CR) is a robust intervention that can prevent and reverse such changes, resulting in reduced ageassociated disease and increased lifespan across a wide range of species. Moreover, a link between the extent of restriction and increased lifespan has also been established. Though widely studied, the mechanisms behind the beneficial effects of CR have yet to be fully understood. Consequently, I investigated metabolomic changes in the liver, plasma, brown adipose tissue (BAT) and cerebellum in five month old male C57BL/6 mice undergoing three months of either 10, 20, 30 or 40% CR, in addition to 12 hour and 24 hour ad libitum fed groups. Behavioural, physiological and molecular data was collected on each individual mouse and I used this information, in addition to my own metabolomic data to determine associations between phenotypic changes with graded CR. My results indicate that increasing CR resulted in greater numbers of significantly differentiated metabolites across all four tissues, and these were related to changes across sphingolipids, carnitines, bile acids, vitamins and amino acids. Metabolic remodelling in the liver indicated a shift from lipogenesis to lipolysis and changes in the plasma indicated an increase in absorption of vitamins from the stomach and colon. Changes in neurotransmitters and their precursors suggested activity and temperature driven BAT activation, in addition to an increase in antioxidant power, this was also seen in the cerebellum where metabolites associated with signalling in the hypothalamus were increased in a graded fashion with CR. In all tissues changes were linked with behaviours that accompany hunger signalling such as increased food anticipatory activity and reduced body temperature. Together, these changes reflect multi-tissue beneficial effects of CR, which may function to alleviate age-related comorbidities.
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Padronização dos extratos polares das partes aéreas de Actinocephalus divaricatus (Körn.) Sano (Eriocaulaceae) /Silva, Ana Caroline Zanatta. January 2016 (has links)
Orientadora: Lourdes Campaner dos Santos / Banca: Ana Helena Januário / Banca: Anne Ligia Dokkedal Bosqueiro / Resumo: Este trabalho descreve a caracterização química dos extratos metanólicos de capítulos, escapos e folhas de Actinocephalus divaricatus, descrito pela primeira vez na literatura. Primeiramente, as amostras foram analisadas por cromatografia líquida de alta eficiência (HPLC) acoplada com detector de arranjo de fotodiodos (PAD) e por espectrometria de massas em tandem acoplado a um orbitrap com interface de ionização por electrospray, usando um sistema LC para a separação cromatográfica dos metabólitos (HPLC-ESI-HRMS). Esta estratégia permitiu explorar e diferenciar os metabólitos secundários presentes, sendo identificados 31 compostos incluindo 12 flavonoides, 5 naftopiranonas e 14 saponinas. Esta análise diferencial das três partes da planta contribuirá com a discussão do gênero Actinocephalus, uma vez que os estudos na literatura são relatados apenas para Paepalanthus sect. Actinocephalus. A separação dos metabólitos presentes nos extratos metanólicos dos escapos e folhas foi realizada empregando técnicas cromatográficas, como Sephadex, MPLC, HPLC-PAD e HPLC-IR, em que foi possível obter treze compostos: três ácidos fenólicos, sete flavonoides, duas naftopiranonas e uma saponina. As estruturas de todos os compostos foram determinadas por análise dos dados obtidos por RMN mono e bidimensionais. A padronização dos extratos metanólicos foi realizada por meio da quantificação dos flavonoides e naftopiranonas por HPLC-PAD. A metodologia foi validada avaliando-se os parâmetros de s... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: This work describes the chemical characterization of the methanolic extracts of the capitulae, scapes and leaves from Actinocephalus divaricatus, described the first time in the literature. First, the samples were analyzed by high-performance liquid chromatography (HLPC) coupled with a photodiode array detector (PAD) and mass spectrometry tandem coupled to an Orbitrap with electrospray ionization interface using an LC system for separating chromatographic metabolites (HPLC-ESI-HRMS). This strategy has allowed us to explore a differentiate the secondary metabolites present, identified as 31 compounds comprising 12 flavonoids, 5 naphthopyranones and 14 saponins. This differential analysis of the three parts of the plant contributes to the discussion of the Actinocephalus genus, since the studies reported in the literature are only of the Paepalanthus sect. Actinocephalus. The separation of the metabolites present in the methanolic extracts of the scapes and leaves was performed using chromatographic techniques, such as Sephadex, MPLC, HPLC-PAD and HPLC-IR. It was possible to obtain thirteen compounds: three phenolic acids, seven flavonoids, two naphthopyranones and one saponin. The structures of all the compounds were determined by data analysis by mono and bidimensional NMR. The standardization of the methanolic extracts was performed by the quantification of flavonoids and naphthopyranones by HPLC-PAD. The methodology was validated by evaluating the parameters of selectivit... (Complete abstract click electronic access below) / Mestre
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Studies of fungal natural products and the degradation of A- and SS-trenboloneLong, Sarah Ann 01 July 2014 (has links)
No description available.
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Biosynthesis and translocation of secondary metabolite glycosides in the grapevine Vitis vinifera L.Gholami, Mansour. January 1996 (has links) (PDF)
Copies of author's previously published articles inserted. Bibliography: leaves 121-144. This study investigates the site of biosynthesis of flavour compounds in the grapevine. Most of the secondary metabolites, including flavour compounds, are glycosylated and stored in plant tissues as glycosides. The chemical properties of these compounds, especially their water solubility, suggests that glycosides might be forms of translocated secondary metabolites in plants.
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Studies on nitrogen containing secondary metabolites from terrestrial and marine originBarrios Sosa, Ana Carolina 21 August 2001 (has links)
PART I. A deuterium exchange analysis of 2,5-dihydroxyacetanilide (5)
in the absence and presence of DHAE II was performed to test the
nucleophilicity of the substrate in the absence and presence of catalyst. In
addition, inhibition studies using 1,4-dihydroxybenzene were performed to
determine the role that the N-acetyl side chain group plays in the formation of a stable substrate-enzyme complex. 1,4-Dihydroxybenzene was found to be a
weak inhibitor, indicating that the N-acetyl functionality may play a crucial role in forming stable enzyme-substrate interactions. The synthesis of
dihydroquinoline 7 was pursued to investigate the enzyme substrate interactions
between DHAE and a substrate where the N-acetyl side chain has been fixed to a
particular orientation. Efforts towards formation of the C6-C7 bond as a key
step in the synthesis of dihydroquinoline 7 using palladium couplings,
organocuprates, Lewis acid catalysts, and aza-Claisen reactions were pursued.
To complement the results obtained, the electron distribution in amide 21 was
calculated using Semi Empirical methods. The results revealed that the electron
density in the aromatic ring is centered around C4, suggesting that this is the
most nucleophilic carbon in the ring.
PART II. Slagenins A (1), B (2), and C (3) were synthesized by β-functionalization
of olefin 14. The desired tetrahydrofuroimidazolidin-2-one system was achieved by intramolecular oxidative addition of alcohol 4 to the
imidazolone ring. When this reaction was carried out in the presence of
methanol slagenins B (2) and C (3) were obtained in good yield. Heating 2 and
3 in aqueous acid gave slagenin A (1) as the sole product. (Z)-debromoaxinohydantoin (17) was synthesized by intramolecular cyclization of
α-methoxy imidazolone 11b under acidic conditions followed by a double
oxidation reaction to furnish the hydantoin-lactam functionality. These
conditions were originally developed for a practical synthesis of the related
alkaloid (Z)-debromohymenialdisine (20). A series of acid and base catalyzed
reactions of imidazoles bearing an α-β unsaturated system or a β-halogen
functionality showed that cyclizations via an S[subscript N]2 path favor formation of an
oxazoline ring system. Preliminary studies using pyrrolocarboxamideacetals
suggest that β-ketone 73 would be an appropriate substrate for the formation of
the pyrrolopyrazine system in the agelastatins. / Graduation date: 2002
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Biosynthesis, production and structural studies of secondary metabolites in cultured marine cyanobacteriaVulpanovici, Florina Alexandra 23 July 2003 (has links)
This thesis details investigations of marine cyanobacterial secondary
metabolism, with emphasis on a strain of Phormidium sp. collected in Indonesia.
These studies assessed the effects of nineteen putative elicitor compounds on the
growth and metabolite production of five species of marine cyanobacteria,
biosynthetic investigation of an intriguing secondary metabolite, phormidolide,
and the discovery of one novel halogenated peptide, phormidamide.
The growth, biomass production and the ratio of the components of the
extract were affected by some of the elicitors in most of the cyanobacterial species
tested. However, production of a novel secondary metabolite or a significant
change in the bioactivity of the extracts was not observed.
Biosynthetic investigations of a brominated brine shrimp toxic polyketide,
phormidolide, were conducted on a cultured Phormidium sp. strain originally
isolated from Indonesia. Stable isotope feeding experiments confirmed its
polyketide nature and established a new example of a general trend in
cyanobacterial metabolism where both S-adenosyl methionine and C2 of acetate
contribute to the biogenesis of pendant methyl groups. At the same time, feedings
with deuterated acetate provided insight into the HMG-CoA synthase-like
mechanism by which addition of pendant methyl groups from C2 of acetate takes
place.
Studies of phormidolide production in bromine-depleted medium showed
that two analogs are produced, debromophormidolide with a terminal olefin in
place of the vinyl bromide, and iodophormidolide, introducing iodine in place of
bromine from the trace amounts present in the medium. Supplementation of the
bromine-depleted culture medium with iodine resulted in a 10-fold increase of
iodophormidolide production, while bromine supplementation resulted in a more
moderate (2.5 fold) enhancement in phormidolide yield.
A novel halogenated cytotoxic peptide, phormidamide, was isolated and a
planar structure is proposed, pending confirmation by X-ray crystallographic
analysis. Phormidamide contains a unique bromophenylalanine functionality,
three chlorine atoms, and a very high number of quaternary carbon atoms which
have hindered structural elucidation efforts through spectroscopic methods. / Graduation date: 2004
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Structure and biosynthesis of marine cyanobacterial natural products : development and application of new NMR methodsMarquez, Brian L. 29 June 2001 (has links)
This thesis is an account of my explorations into the field of natural products
chemistry. These investigations led to the discovery of several novel secondary
metabolites isolated from the marine cyanobacterium Lyngbya majuscula. In addition,
biosynthetic investigations were undertaken using stable isotope-labeled precursors.
The dominant role that NMR spectroscopy plays in the field of natural products
chemistry has led to the development of several novel pulse sequences.
Hectochlorin was discovered during a phytochemical investigation of a
cultured L. majuscula originally collected off the coast of the Caribbean Island,
Jamaica. The absolute stereochemistry was determined by X-ray crystallography.
Through a series of biological evaluations, this compound was found to stimulate actin
polymerization.
The jamaicamide class of compound was isolated from the same organism that
yielded hectochlorin. The structures were elucidated utilizing a variety of NMR
methods, including a newly developed pulse sequence. Because the producing
organism was in culture, a biosynthetic pathway investigation ensued to elucidate the
carbon framework in jamaicamide A.
The marine natural product barbamide is intriguing due to the incorporation of
a trichloromethyl group into its molecular constitution. Further investigation into the
timing of the chlorination reaction has been pursued. In addition, the isolation of
dechlorobarbamide and the determination of the absolute stereochemistry assignment
of barbamide was accomplished.
A reevaluation of the stereochemistry of antillatoxin necessitated a correction
in the original assignment. Four antillatoxin stereoisomers were obtained from a
collaborator and found to possess differing levels of biological activity. The three
dimensional solution structures of these isomers were evaluated in an effort to
understand the role these stereochemical features play in the observed bioactivity. The
structures were determined utilizing NMR-derived constraints applied to molecular
modeling calculations.
The development of two new pulse sequences for the determination of long-range
heteronuclear coupling constants was also accomplished. The 1,1 ADEQUATE
experiment was modified to yield an ACCORDIAN experiment which can be
optimized to observe of a wide range of ��J[subscript cc] couplings. This new experiment is
demonstrated for a model compound as well as for the new marine natural product
jamaicamide A. / Graduation date: 2002
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Expression of secondary metabolites following manipulations of the C:N ratio in spotted knapweed, Centaurea maculosa Lam.Brodhagen, Marion L. 12 June 1998 (has links)
Spotted knapweed, Centaurea maculosa Lam. (Compositae) is an extremely
successful introduced weed species in the northwestern United States. Multiple factors
may be responsible for its success, including chemical defense. Two different types of
putative chemical defense agents are the focus of this thesis. The first is a bitter-tasting
sesquiterpene lactone, cnicin, which occurs at high concentrations in foliar tissues; the
second is a group of polyacetylenic compounds produced in the roots. This study
represents the first designation of structural identities to polyacetylenic compounds from
North American populations of C. maculosa. Both cnicin and polyacetylenic compounds
have demonstrated biological activity, suggesting roles in chemical defense. In order to
test predictions of chemical defense hypotheses for this plant, concentrations of cnicin
and polyacetylenes were measured in a greenhouse experiment in response to varying soil
nitrogen and light availability. Light and soil nitrogen availability were important in
determining concentrations and content of cnicin, whereas polyacetylene concentrations
were not significantly affected by differences in these environmental parameters. Cnicin concentrations were also measured in a field experiment in response to varying levels of
soil nitrogen and water. No significant differences in cnicin concentrations were
observed among treatments in either young (rosette-stage) or mature aerial tissues. / Graduation date: 1999
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Bioactive secondary metabolites from marine algae and study of oxidized anandamide derivativesYoo, Hye-Dong 13 October 1997 (has links)
My investigations of the natural products of marine algae have resulted in
the discovery of several new secondary metabolites. Bioassay-guided
fractionation led to the isolation of these new compounds and spectroscopic
analysis was utilized in their structural characterization.
Two new and potent antimitotic metabolites, curacins B and C, were
isolated from a Curacao collection of Lyngbya majuscula. In addition, four
curacin A analogs were prepared by semisynthetic methods. The structures of
the new curacins and the curacin A analogs were determined by spectroscopic
analysis in comparison with curacin A. The biological properties of the new
natural products and synthetic derivatives of curacin A were examined.
Investigations of another Curacao collection of L. majuscula revealed a
new cytotoxic lipopeptide, microcolin C. Microcolin C was found to have an
interesting profile of cytotoxicity to human cancer-derived cell lines.
A new metabolite, vidalenolone, was isolated from an Indonesian red
alga Vidalia sp. The structure of this new cyclopentenolone-containing
compound was determined by a combination of spectroscopic methods.
Filamentous cells isolated from female gametophytes of the brown alga
Laminaria saccharina were cultured in flasks or bioreactors. These cultures
produced a variety of w6-lipoxygenase metabolites: 13-hydroxy-9,11-octadecadienoic acid (13-HODE), 13-hydroxy-6,9,11,15-octadecatetraenoic acid (13-HODTA), and 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE).
Five oxidized anandamide derivatives were prepared from anandamide through autoxidation in an exploration of ligand binding to the cannabinoid receptor. Their structures were determined by a combination of NMR spectroscopy and GC-MS. The cannabinoid receptor binding affinity of these derivatives was evaluated. This study revealed the following trend in activity: anandamide > 15- > 9- > 8- > 11- > 5-hydroxyanandamide. / Graduation date: 1998
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Novel bioactive secondary metabolites from the marine cyanobacterium Lyngbya majusculaWu, Min, 1963- 13 September 1996 (has links)
Marine algae have been recognized as a rich resource of new
and unusual organic molecules with diverse biological properties.
The current need to develop new antifungal, anticancer, antibiotic
and antiviral drugs has led to an intense research effort into the
discovery, isolation and structure determination of potential
medicinal agents from marine algae.
In the past two years, I have participated in a drug discovery
program designed for antitumor, antifungal and other agents of
potential pharmaceutical utility from the marine cyanobacterium
Lyngbya majuscula. This research utilized modern chromatographic
and spectrochemical techniques including 2D NMR spectroscopy.
Brine shrimp toxicity guided the fractionation that led to the
discovery of the biologically active compound kalkitoxin from a
Curacao Lyngbya majuscula extract. The structure of this new
thiazoline ring-containing lipid was determined spectroscopically
by interpretation of 2D-NMR experiments, including heteronuclear
multiple quantum coherence (HMQC), heteronuclear multiple-bond
coherence spectroscopy (HMBC) and ��H-��H COSY at room
temperature and elevated temperature. Kalkitoxin shows modest
molluscicidal toxicity, good brine shrimp toxicity and extremely
potent ichthyotoxicity.
From the same extract of Lyngbya majuscula, I also isolated
two other secondary metabolites, malyngamide J and malyngamide
L. The structures of these new compounds, including
stereochemistry, were determined by spectroscopic techniques
including 2D-NMR experiments and by comparison with other
known malyngamides. / Graduation date: 1997
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