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Biological Investigations (biological + investigation)
Selected AbstractsPhytochemical and Biological Investigation of Hymenocallis littoralisSalisb.CHEMISTRY & BIODIVERSITY, Issue 2 2008Amina Abstract A phytochemical investigation of the bulbs and flowers of Hymenocallis littoralisSalisb., cultivated in Egypt, was carried out, which resulted in the isolation of four alkaloids, lycorine (1), hippeastrine (2), 11-hydroxyvittatine (3), and (+)-8- O -demethylmaritidine (4), and of two flavonoids, quercetin 3,- O -glucoside (5), and rutin (6). The volatile constituents of the plant flowers were analyzed for the first time by GC/MS, which led to the identification of 26 known compounds (Table,1). Finally, the antimicrobial activity of the petroleum ether extract of the flowers of H. littoralis was investigated. [source] Embryonic reversions and lineage infidelities in tumour cells: genome-based models and role of genetic instabilityINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 2 2005Leon P. Bignold Summary Reversions to ,embryonic precursor'-type cells and infidelities of tumour cell lineage (including metaplasias) have been recognized as aspects of various tumour types since the 19th century. Since then, evidence of these phenomena has been obtained from numerous clinical, biochemical, immunological and molecular biological studies. In particular, microarray studies have suggested that ,aberrant' expressions of relevant genes are common. An unexplained aspect of the results of these studies is that, in many tumour types, the embryonic reversion or lineage infidelity only occurs in a proportion of cases. As a parallel development during the molecular biological investigation of tumours over the last several decades, genetic instability has been found much more marked, at least in some preparations of tumour cells, than that identified by means of previous karyotypic investigations of tumours. This study reviews examples of embryonic reversion and lineage infidelity phenomena, which have derived from the various lines of investigation of cancer over the last 150 or so years. Four categories of circumstances of the occurrence of embryonic reversions or lineage infidelities have been identified , (i) as part of the defining phenotype of the tumour, and hence being presumably integral to the tumour type, (ii) present ab initio in only some cases of the tumour type, and presumably being regularly associated with, but incidental to, the essential features of the tumour type, (iii) occurring later in the course of the disease and thus being possibly a manifestation of in vivo genetic instability and ,tumour progression' and (iv) arising probably by genetic instability, during the processes, especially cell culture, associated with ex vivo investigations. Genomic models are described which might account for the origin of these phenomena in each of these circumstances. [source] Prasinoxanthin-constaining Prasinophyceae Discovered in Jiaozhou Bay, ChinaJOURNAL OF INTEGRATIVE PLANT BIOLOGY, Issue 4 2007Zhi-Gang Yu Abstract The class Prasinophyceae (Chlorophyta) contains some photosynthetic eukaryotic ultraplankton species characterized by containing prasinoxanthin. The existence and abundance of these organisms can be estimated by the diagnostic pigment. We detected the unique pigments of prasinoxanthin-containing Prasinophyceae in Jiaozhou Bay, China using high performance liquid chromatography (HPLC). This was the first finding of this kind in Chinese seas. Using the ratio of prasinoxanthin to chlorophyll a, the abundance of prasinoxanthin-containing Prasinophyceae has been calculated. The average contribution of prasinoxanthin-containing Prasinophyceae to the chlorophyll a pool was 8.5% and 17.0% in May and August 2004 in Jiaozhou Bay, and the maximums were 25.9% and 36.3%. Size fractionated pigment analysis suggested that more than 80% of prasinoxanthin were in the fraction of 2-20 ,m. According to the results of pigment and morphological analysis, the possible genera of prasinoxanthin-containing Prasinophyceae and the reasons for causing this high abundant phytoplankton in Jiaozhou Bay were discussed. This kind of phytoplankton can not be discovered in traditional biological investigation, but its contribution to the coastal ecosystem is significant enough to be studied further. [source] Genomic repertoire of human mesangial cells: comprehensive analysis of gene expression by cDNA array hybridizationNEPHROLOGY, Issue 4 2000Naohiro Yano SUMMARY: Knowing when and where a gene is expressed in a cell often provides a strong clue as to its physiological role. It is estimated the human genome contains 80 000,100 000 genes. Assessment of gene activity on a global genome-wide scale is a fundamental and newly developed experimental strategy to expand the scope of biological investigation from a single gene to studying all genes at once in a systematic way. Capitalizing on the recently developed methodology of cDNA array hybridization, we monitored the simultaneous expression of thousands of genes in primary human mesangial cells. Complex ,- 33P-labelled cDNA probes were prepared from cultured mesangial cells. The probe was hybridized to a high-density array of 18 326 paired target genes. The radioactive hybridization signals were analysed by phosphorimager. Bioinformatics from public genomic databases was utilized to assign a chromosomal location of each expressed transcript. Approximately 7460 different gene transcripts were detected in mesangial cells. Close to 13% (957 genes) were full-length mRNA human transcripts (HTs), the remainder 6503 being expressed sequence tags (ESTs). Using special imaging computer software, the transcriptional level of the 957 HTs was compared with the expression of the ribosomal protein S28 (housekeeping gene). The HTs were also classified by function of the gene product and listed with information on their chromosomal loci. To allow comparison between clinical and experimental studies of gene expression, the detected human gene transcripts were cross-referenced to orthologous mouse genes. Thus, the presented data constitute a quantitative preliminary blueprint of the transcriptional map of the human mesangial cell. The information may serve as a resource for speeding up the discovery of genes underlying human glomerular diseases. The complete listing of the full-length expressed genes is available upon request via E-mail: (Abdalla_Rifai@Brown.edu). [source] Strategic shotgun proteomics approach for efficient construction of an expression map of targeted protein families in hepatoma cell linesPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 12 2003Chih-Lei Lee Abstract An expression map of the most abundant proteins in human hepatoma HepG2 cells was established by a combination of complementary shotgun proteomics approaches. Two-dimensional liquid chromatography (LC)-nano electrospray ionization (ESI) tandem mass spectrometry (MS/MS) as well as one-dimensional LC-matrix-assisted laser desorption/ionization MS/MS were evaluated and shown that additional separation introduced at the peptide level was not as efficient as simple prefractionation of protein extracts in extending the range and total number of proteins identified. Direct LC-nanoESI MS/MS analyses of peptides from total solubilized fraction and the excised gel bands from one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis fractionated insolubilized fraction afforded the best combination in efficient construction of a nonredundant cell map. Compiling data from multiple variations of rapid shotgun proteomics analyses is nonetheless useful to increase sequence coverage and confidence of hits especially for those proteins identified primarily by a single or two peptide matches. While the returned hit score in general reflects the abundance of the respective proteins, it is not a reliable index for differential expression. Using another closely related hepatoma Hep3B as a comparative basis, 16 proteins with more than two-fold difference in expression level as defined by spot intensity in two-dimensional gel electrophoresis analysis were identified which notably include members of the heat shock protein (Hsp) and heterogeneous nuclear ribonucleoprotein (hnRPN) families. The observed higher expression level of hnRNP A2/B1 and Hsp90 in Hep3B led to a search for reported functional roles mediated in concert by both these multifunctional cellular chaperones. In agreement with the proposed model for telomerase and telomere bound proteins in promoting their interactions, data was obtained which demonstrated that the expression proteomics data could be correlated with longer telomeric length in tumorigenic Hep3B. This biological significance constitutes the basis for further delineation of the dynamic interactions and modifications of the two protein families and demonstrated how proteomic and biological investigation could be mutually substantiated in a productive cycle of hypothesis and pattern driven research. [source] Old Molecules for New Receptors: Trp(Nps) Dipeptide Derivatives as Vanilloid TRPV1 Channel BlockersCHEMMEDCHEM, Issue 4 2006Angeles Bonache Dr. Abstract The transient receptor potential vanilloid member 1 (TRPV1), an integrator of multiple pain-producing stimuli, is regarded nowadays as an important biological target for the discovery of novel analgesics. Here, we describe the first experimental evidence for the behavior of an old family of analgesic dipeptides, namely Xaa-Trp(Nps) and Trp(Nps)-Xaa (Xaa=Lys, Arg) derivatives, as potent TRPV1 channel blockers. We also report the synthesis and biological investigation of a series of new conformationally restricted Trp(Nps)-dipeptide derivatives with improved TRPV1/NMDA selectivity. Compound 15,b, which incorporates an N-terminal 2S -azetidine-derived Arg residue, was the most selective compound in this series. Collectively, a new family of TRPV1 channel blockers emerged from our results, although further modifications are required to fine-tune the potency/selectivity/toxicity balance. [source] Lithium response across generationsACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2009P. Grof Objective:, To describe and integrate observations from bipolar patients responsive to lithium stabilization and their children. Method:, Selected findings are described from the clinical and biological investigations of adults meeting research criteria for bipolar disorder and for responsiveness to lithium stabilization; and from prospective studies of the children of lithium responders and non-responders. Results:, Response to prophylactic lithium identifies a valid subtype of bipolar disorder, however the search for biological markers of lithium response, while promising, has so far remained inconclusive. Adult responders to lithium stabilization exhibit definable clinical features which are also observable in their affected children. In prospective studies the children of bipolar parents develop symptoms earlier than reported previously, with marked differences between the offspring of lithium responders and non-responders. The illness evolves in predictable clinical stages, first from non-specific sleep and anxiety disorders to mood symptoms and then, often starting in adolescence, major depressive and later activated episodes. Conclusion:, Investigating and comparing unequivocal responders and non-responders to long-term lithium treatment and their offspring is a fertile research strategy for addressing a multitude of clinical and research questions. [source] Synthesis and Mass Spectrometric Analysis of CyclostellettaminesH, I, K and LEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 5 2006Achim Grube Abstract Very recently the new cyclostellettamines H, I, K and L were identified from a Brazilian sponge of the genus Pachychalina. They were isolated together with the known cyclostellettamines A,G in a mixture of only 1.5 mg. To obtain further material for biological investigations, the synthesis of the four new cyclostellettamines has been carried out. Since mass spectrometry plays an essential role in identifying these compounds a systematic analysis of the cyclostellettamines is discussed. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Potamogeton -Hybriden in Deutschland,FEDDES REPERTORIUM, Issue 5-6 2008G. Wiegleb Prof. Dr. Alle in Deutschland nachgewiesenen Potamogeton -Hybriden werden aufgelistet und beschrieben. Bestimmungsprobleme, Verbreitung und Häufigkeit werden jeweils diskutiert. Potamogeton -Hybriden sind seit mehr als 200 Jahren aus Deutschland bekannt. Insgesamt sind 16 Taxa sicher nachgewiesen. Davon sind nur P. × angustifolius, P. × nitens und P. × salicifolius verbreitet und häufig und treten in vitalen Populationen auf. Drei weitere Taxa kommen wahrscheinlich vor, bedürfen aber noch der endgültigen Bestätigung. Fünf in der Literatur genannte Taxa wurden gestrichen. Weitere Aufsammlungen und molekulargenetische Untersuchungen der kritischen Fälle sind notwendig. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) Potamogeton hybrids in Germany All Potamogeton hybrids occurring in Germany are listed and described. Identification problems, distribution and frequency are discussed for each taxon. Potamogeton hybrids from Germany have been studied since more than 200 years. Today the occurrence of 16 taxa has been verified beyond doubt. Only P. × angustifolius, P. × nitens, and P. × salicifolius are widely distributed and occur frequently in vital populations. Three additional taxa are likely to occur but need further verification. Five taxa reported in literature are excluded. Further collections and molecular biological investigations of critical taxa are mandatory. [source] Interactions between genetic and reproductive factors in breast cancer risk in a population-based sample of African-American familiesGENETIC EPIDEMIOLOGY, Issue 4 2002Valérie Chaudru Abstract Incidence of breast cancer (BC) varies among ethnic groups, with higher rates in white than in African-American women. Until now, most epidemiological and genetic studies have been carried out in white women. To investigate whether interactions between genetic and reproductive risk factors may explain part of the ethnic disparity in BC incidence, a genetic epidemiology study was conducted, between 1989 and 1994, at the Howard University Cancer Center (Washington, DC), which led to the recruitment of 245 African-American families. Segregation analysis of BC was performed by use of the class D regressive logistic model that allows for censored data to account for a variable age of onset of disease, as implemented in the REGRESS program. Segregation analysis of BC was consistent with a putative dominant gene effect (P < 0.000001) and residual sister-dependence (P < 0.0001). This putative gene was found to interact significantly with age at menarche (P = 0.048), and an interaction with a history of spontaneous abortions was suggested (P = 0.08). A late age at menarche increased BC risk in gene carriers but had a protective effect in non-gene carriers. A history of spontaneous abortions had a protective effect in gene carriers and increased BC risk in non-gene carriers. Our findings agree partially with a similar analysis of French families showing a significant gene × parity interaction and a suggestive gene × age at menarche interaction. Investigating gene × risk factor interactions in different populations may have important implications for further biological investigations and for BC risk assessment. Genet. Epidemiol. 22:285,297, 2002. © 2002 Wiley-Liss, Inc. [source] Characterisation of Heterotrophic Microorganisms Isolated form the "Grotta Azzura" of Cape Palinuro (Salerno, Italy)MARINE ECOLOGY, Issue 2002Francesco Canganella Abstract. Hydrothermal vent ecosystems have been extensively investigated during the last 20 years; shallow water hot springs (typically found below 50 m depth) have also been studied, and from these ecosystems many thermophilic and hyperthermophilic organisms were isolated and described. The submarine caves of Cape Palinuro were discovered long ago, but only during the last decades were geological and biological investigations carried out, yielding a large number of reports on this fascinating environment. During the last two years, several samples of water, mud, and/or bacterial mat were collected within the "Grotta Azzurra", and enrichment experiments were performed using peptone, starch, glucose or pullulan as main organic nutrients. Many heterotrophic strains were isolated and most of them grew optimally between 37 and 43 ° C with the addition of 0-2 % NaCl. Growth was usually observed between 10 and 50 ° C the range of growth pH was 4 to 9, and NaCl concentrations up to 10,12 % were tolerated in most cases. The analysis of 16S rDNA performed with the most representative isolates showed a close phylogenetic relationship with the genera Bacillus, Vibrio, Citrobacter and Escherichia. Moreover, an isolate showing morphological and physiological similarities with the genus Enterococcus was characterised and taxonomically described based on the 16S rDNA sequence. [source] N -Malonyl-1,2-dihydroisoquinoline as a Novel Carrier for Specific Delivery of Drugs to the BrainARCHIV DER PHARMAZIE, Issue 1 2010Mohamed Abdel-Aziz Abstract N -Malonyl-1,2-dihydroisoquinoline derivatives were synthesized and investigated as a novel carrier system for site-specific and sustained delivery of drugs to the brain. Such carriers are expected to be stable against air oxidation due to the presence of the carbonyl group close to nitrogen of the dihydroisoquinoline. Reduction of the prepared isoquinolinium quaternary derivatives with sodium dithionite afforded a novel group of N -malonyl-1,2-dihydroisoquinoline chemical delivery systems (CDS). The synthesized N -malonyl-1,2-dihydroisoquinoline chemical delivery systems were subjected to various chemical and biological investigations to evaluate their ability to cross the blood-brain barrier (BBB), and to be oxidized biologically into their corresponding quaternary derivatives. The in-vitro oxidation studies showed that the designed N -malonyl-1,2-dihydroisoquinoline chemical delivery system could be oxidized into its corresponding quaternary derivatives at an adequate rate. The in-vivo distribution studies showed that these N -malonyl-1,2-dihydroisoquinoline chemical delivery systems were able to cross the blood-brain barrier at detectable concentrations. [source] New Peptolides from the Cyanobacterium Nostoc insulare as Selective and Potent Inhibitors of Human Leukocyte ElastaseCHEMBIOCHEM, Issue 16 2008Christian Mehner Abstract Eight new cyanopeptolins (insulapeptolides A,H) were obtained from the cyanobacterium Nostoc insulare. Their isolation was guided by their bioactivity toward the target enzyme human leukocyte elastase, molecular biological investigations, and MALDI-TOF analysis. These peptides are selective inhibitors of human leukocyte elastase with activities in the nanomolar range. Insulapeptolide D (4) was the most potent compound with an IC50 value of 85 nM (Ki value of 36 nM). [source] Exo-Mechanism Proximity-Accelerated Alkylations: Investigations of Linkers, Electrophiles and Surface Mutations in Engineered Cyclophilin,Cyclosporin SystemsCHEMBIOCHEM, Issue 5 2005Konstantin Levitsky Abstract Investigations on the scope and utility of exo-mechanism proximity-accelerated reactions in engineered receptor,ligand systems are reported. We synthesized a series of electrophilic cyclosporin (CsA) derivatives by varying electrophiles and linker lengths, prepared a series of nucleophilic cysteine mutations on the surface of cyclophilin A (Cyp), and examined their reactivity and specificity in proximity-accelerated reactions. Acrylamide and epoxide electrophiles afforded useful reactivity and high specificity for alkylation of engineered receptors in Jurkat cell extracts. We found that remote cysteines (>17 Å from the ligand) could be alkylated with useful rates under physiological conditions. The results from mutations of the receptor surface suggest that the dominant factors governing the rates of proximity-accelerated reactions are related to the local environment of the reactive group on the protein surface. This study defines several parameters affecting reactivity in exo-mechanism proximity-accelerated reactions and provides guidance for the design of experiments for biological investigations involving proximity-accelerated reactions. [source] The World of , - and , -Peptides Comprised of Homologated Proteinogenic Amino Acids and Other ComponentsCHEMISTRY & BIODIVERSITY, Issue 8 2004Dieter Seebach The origins of our nearly ten-year research program of chemical and biological investigations into peptides based on homologated proteinogenic amino acids are described. The road from the biopolymer poly[ethyl (R)-3-hydroxybutanoate] to the , -peptides was primarily a step from organic synthesis methodology (the preparation of enantiomerically pure compounds (EPCs)) to supramolecular chemistry (higher-order structures maintained through non-covalent interactions). The performing of biochemical and biological tests on the , - and , -peptides, which differ from natural peptides/proteins by a single or two additional CH2 groups per amino acid, then led into bioorganic chemistry and medicinal chemistry. The individual chapters of this review article begin with descriptions of work on , -amino acids, , -peptides, and polymers (Nylon-3) that dates back to the 1960s, even to the times of Emil Fischer, but did not yield insights into structures or biological properties. The numerous, often highly physiologically active, or even toxic, natural products containing ,- and ,-amino acid moieties are then presented. Chapters on the preparation of homologated amino acids with proteinogenic side chains, their coupling to provide the corresponding peptides, both in solution (including thioligation) and on the solid phase, their isolation by preparative HPLC, and their characterization by mass spectrometry (HR-MS and MS sequencing) follow. After that, their structures, predominantly determined by NMR spectroscopy in methanolic solution, are described: helices, pleated sheets, and turns, together with stack-, crankshaft-, paddlewheel-, and staircase-like patterns. The presence of the additional CC bonds in the backbones of the new peptides did not give rise to a chaotic increase in their secondary structures as many protein specialists might have expected: while there are indeed more structure types than are observed in the , -peptide realm , three different helices (10/12 -, 12 -, and 14 -helix) if we include oligomers of trans -2-aminocyclopentanecarboxylic acid, for example , the structures are already observable with chains made up of only four components, and, having now undergone a learning process, we are able to construct them by design. The structures of the shorter , -peptides can also be reliably determined by molecular-dynamics calculations (in solution; GROMOS program package). Unlike in the case of the natural helices, these compounds' folding into secondary structures is not cooperative. In , - and , -peptides, it is possible to introduce heteroatom substituents (such as halogen or OH) onto the backbones or to incorporate heteroatoms (NH, O) directly into the chain, and, thanks to this, it has been possible to study effects unobservable in the world of the , -peptides. Tests with proteolytic enzymes of all types (from mammals, microorganisms, yeasts) and in vivo examination (mice, rats, insects, plants) showed , - and , -peptides to be completely stable towards proteolysis and, as demonstrated for two , -peptides, extraordinarily stable towards metabolism, even when bearing functionalized side chains (such as those of Thr, Tyr, Trp, Lys, or Arg). The , -peptides so far examined also normally display no or only very weak cytotoxic, antiproliferative, antimicrobial, hemolytic, immunogenic, or inflammatory properties either in cell cultures or in vivo. Even biological degradation by microbial colonies of the types found in sewage-treatment plants or in soil is very slow. That there are indeed interactions of ,- and ,-peptides with biological systems, however, can be seen in the following findings: i) organ-specific distribution takes place after intravenous (i.v.) administration in rats, ii) transport through the intestines of rodents has been observed, iii) , -peptides with positively charged side chains (Arg and Lys) settle on cell surfaces, are able to enter into mammalian cells (fibroplasts, keratinocytes, HeLa cells), and migrate into their cell nuclei (and nucleoli), and iv) in one case, it has already been established that a , -peptide derivative can up- and down-regulate gene expression rates. Besides these less sharply definable interactions, it has also been possible to construct , - and , -peptide agonists of naturally occurring peptide hormones, MHC-binding , -peptides, or amphipathic , -peptide inhibitors of membrane-bound proteins in a controlled fashion. Examples include somatostatin mimics and the suppression of cholesterol transport through the intestinal brush-border membrane (by the SR-BI-protein). The results so far obtained from investigations into peptides made up of homologues of the proteinogenic amino acids also represent a contribution to deepening of our knowledge of the natural peptides/proteins, while potential for biomedicinal application of this new class of substances has also been suggested. [source] | ||||||||||||||||