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At least 631 records · Page 35Linked to original sources
PubMed2004

Natural products as a hunting ground for combinatorial chemistry.

Natural products have a long history of success as biologically active leads for therapeutic agents. The ability to prepare analogues and to discover structure-activity relationships is necessary to truly harness the potential of natural products. Recently, combinatorial chemistry has risen to this challenge, and even fairly complex natural products can be targeted for parallel synthesis. Academic and industrial efforts have employed natural products from the peptide, alkaloid, polyketide, and terpenoid and steroid classes in combinatorial chemistry approaches for the production of medicinally important compounds.

Alkaloids↗
PubMedDate not supplied

Hunting for genes by functional screens.

Advances in high throughput sequencing technologies have led to an explosion of sequence information available for today's researchers. Efforts in the emerging next phase of the genomic era are focusing on the assignment of function to genes uncovered by genome sequencing programs. The main approaches include high throughput mutagenesis, predictions based on homology in primary sequence, microarray and proteomics. Despite the variety of strategies applied, only 30% of predicted human genes have any function assigned. There is a need, therefore, for additional tools to overcome some of the limitations of existing techniques. In this review we discuss some recent developments and their impact on gene function annotation, especially as they relate to the elucidation of signalling cascades activated by cytokines and growth factors.

Animals↗
PubMed2005

Stable isotope and trace element status of subsistence-hunted bowhead and beluga whales in Alaska and gray whales in Chukotka.

Tissues of bowhead, beluga, and gray whales were analyzed for Ag, Cd, Cu, Se, Zn, THg and MeHg (belugas only). Delta15N and delta13C in muscle were used to estimate trophic position and feeding habitat, respectively. Trace element concentrations in tissues were significantly different among whale species. Hepatic Ag was higher in belugas than bowheads and gray whales. Gray whales had lower Cd concentrations in liver and kidney than bowhead and belugas and a sigmoid correlation of Cd with length was noted for all whales. Renal and hepatic Se and THg were higher in belugas than in baleen whales. The hepatic molar ratio of Se:THg exceeded 1:1 in all species and was negatively correlated to body length. Hepatic and renal Zn in subsistence-harvested gray whales was lower than concentrations for stranded whales. Se:THg molar ratios and tissue concentrations of Zn may show promise as potential indicators of immune status and animal health.

Alaska↗
PubMed2006

Seeking completeness in bacterial mutant hunts.

The identification of most or all of the genetic functions that are required for a particular biological process could be achieved through phenotypic studies of high genome-coverage mutant collections. Technologies for creating such collections, in the form of mixed populations or individually arrayed sequence-defined mutants, are now available for numerous bacterial species. The analysis of mixed mutant collections using microarray-based detection procedures appears to be particularly effective in identifying functions required for complex processes such as virulence. The phenotypic analysis of sequence-defined mutant libraries provides a virtually complete identification of nonessential genes required for processes for which suitable screens can be devised. Such libraries also serve as a source of individual mutants for examining the biological relevance of gene associations revealed by transcriptional profiling or homology.

Bacteria↗
PubMed2004

Hunting for neuronal currents: absence of rapid MRI signal changes during visual-evoked response.

While recent reports have advocated the use of magnetic resonance imaging (MRI) to detect the effects of neuronal currents associated with human brain activity, only preliminary experimental data have been presented so far to demonstrate the feasibility of the method. Furthermore, it has not been adequately demonstrated that (1) MRI can separate neuronal current (NC) effects from other effects such as blood oxygen level-dependent (BOLD) contrast; (2) MRI has adequate sensitivity to detect NCs in vivo. In this work, we introduce a method that can separate slow (e.g., BOLD) processes from potential rapid (e.g., NC) processes and apply this method to investigate whether MRI allows detection of an NC response to a visual stimulus. MRI studies (n = 8) at 3.0 T using a sensitive multichannel detector showed insignificant effects related to NCs (averaged t < 0.05), in the presence of a highly significant BOLD signal (t = 6.15 +/- 0.90). In contrast, magnetoencephalography (MEG) experiments performed under similar conditions on the same subjects showed highly significant electrical activity (t = 7.90 +/- 2.28). It is concluded that, under the conditions used in this study, the sensitivity of MRI to detect evoked responses through NCs is at least an order of magnitude below that of BOLD-based functional MRI (fMRI) or MEG and too low to be practically useful.

Data Interpretation, Statistical↗
PubMed2006

Tracking in the Wlds--the hunting of the SIRT and the luring of the Draper.

Wallerian degeneration of distal axons after nerve injury is significantly delayed in the Wlds mutant mouse. The Wlds protein is a fusion of nicotinamide mononucleotide adenyltransferase-1 (Nmnat1), an essential enzyme in the biosynthesis pathway of nicotinamide adenine dinucleotide (NAD), with the N-terminal 70 amino acids of the Ube4b ubiquitination assembly factor. The mechanism of Wlds action is still enigmatic, although recent efforts suggest that it is indirect and requires sequences flanking or linking the two fused open reading frames. Three papers in this issue of Neuron now show that Wlds action is conserved in Drosophila and that a critical role of Wlds may be the suppression of axonal self-destruct signals that induce Draper-mediated clearance of damaged axons by glial cells.

Animals↗
PubMed2005

Do high TSH values protect against chronic musculoskeletal complaints? The Nord-Trøndelag Health Study (HUNT).

The aim of this large cross-sectional population-based study was to examine a possible positive or negative association between thyroid dysfunction and chronic musculoskeletal complaints (MSC). Between 1995 and 97, all 94,197 adults in Nord-Trøndelag County in Norway were invited to participate in a health survey. A total of 64,787 (69%) responded to questions related to MSC, whereof thyroid-stimulating hormone (TSH) was measured in 34,960 individuals. These included a 5% random sample of women and men 20-40 years of age (n=2165), nearly all women above 40 (n=19,308), a random sample which included 50% of men older than 40 years (n=9983), and 3504 (97%) with self-reported thyroid dysfunction. Among the 64,787 participants, 30,158 (47%) who reported MSC continuously for at least 3 months during the past year where defined as having chronic MSC. Associations between thyroid dysfunction and chronic MSC were assessed in multivariate analyses, estimating prevalence odds ratios (ORs) with 95% confidence intervals (CIs). High TSH values were associated with lower prevalence of chronic MSC at ten anatomical sites among women with no history of thyroid dysfunction. Among these, chronic MSC was less likely (OR=0.6, 95% CI 0.4-0.8) if TSH >or=10 mU/L than in women with normal TSH (0.2-4 mU/L). Chronic MSC was less likely among women with high TSH values. The mechanism is unclear and, theoretically, may reflect a fundamental gender-specific relationship between TSH and pain perception in the central nervous system.

Adult↗
PubMed2005

Amino acid sequence and biological activity of a gamma-conotoxin-like peptide from the worm-hunting snail Conus austini.

A novel 31-residue toxin, named as7a, was isolated and characterized from the venom of Conus austini, a vermivorous cone snail collected in the western Gulf of Mexico. The complete amino acid sequence, TCKQKGEGCSLDVgammaCCSSSCKPGGPLFDFDC, was determined by automatic Edman sequencing after reduction and alkylation. The sequence shows six Cys residues arranged in the pattern that defines the O-superfamily of conotoxins, and the sequence motif -gammaCCS-, which has only been found in the gamma-conotoxin family. The molecular mass of the native peptide was determined by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry, which confirmed the chemical analyses and suggested a free C-terminus. The purified peptide elicited toxic effects in the freshwater snail Pomacea paludosa after intramuscular injection, but it had no effect when injected intracerebrally into mice. The structural similarity of peptide as7a to other gamma-conotoxins suggests that modulation of pacemaker channels could be responsible for its biological activity.

Amino Acid Sequence↗
PubMed2005

A case of promiscuity: Agrobacterium's endless hunt for new partners.

Agrobacterium tumefaciens is a phytopathogenic bacterium that induces the 'crown gall' disease in plants by transfer and integration of a segment of its tumor-inducing (Ti) plasmid DNA into the genome of numerous plant species that represent most of the higher plant families. Recently, it has been shown that, under laboratory conditions, the host range of Agrobacterium can be extended to non-plant eukaryotic organisms. These include yeast, filamentous fungi, cultivated mushrooms and human cultured cells. In this article, we present Agrobacterium-mediated transformation of non-plant organisms as a source of new protocols for genetic transformation, as a unique tool for genomic studies (insertional mutagenesis or targeted DNA integration) and as a useful model system to study bacterium-host cell interactions. Moreover, better knowledge of the DNA-transfer mechanisms from bacteria to eukaryotic organisms can also help in understanding horizontal gene transfer--a driving force throughout biological evolution.

DNA, Bacterial↗
PubMed2004

Techniques: Bioprospecting historical herbal texts by hunting for new leads in old tomes.

Ethnobotany has led to the identification of novel pharmacological agents but many challenges to using ethnobotany as a research tool remain. In particular, the loss of traditional knowledge together with the advent of high-throughput screening has made ethnobotanical techniques laborious and potentially unnecessary. However, historical herbal texts provide a preexisting resource that documents the traditional uses of various species as medicines. As generational losses of traditional knowledge accrue, these herbal texts become increasingly valuable. The methodology for extracting useful information contained within these resources had been cumbersome and consuming. However, the application of new bioinformatics data-mining systems to herbal texts holds great promise for identifying novel pharmacotherapeutic leads for bioactive compounds.

Ethnobotany↗
PubMed2004

Channel-forming activity in the venom of the cockroach-hunting wasp, Ampulex compressa.

The parasitoid solitary wasp Ampulex compressa uses the cockroach Periplaneta americana as a food supply for its larvae. To subdue its prey, the wasp injects a venom cocktail into the brain of the cockroach. We investigated channel activity of A. compressa venom by collecting venom and incorporating it into a planar lipid bilayer. The venom, reconstituted into the bilayer, showed ion channel activity, forming a fast-fluctuating channel with a small conductance of 20+/-0.1pS, with no voltage sensitivity. These channels were not observed when the venom was digested with proteases before application to the bilayer, but were not affected by exposure to protease after their incorporation into the bilayer, indicating that the active venom component is a peptide. The channels were found to be cation selective with similar selectivity for the monovalent cations K(+), Li(+) and Na(+), but showed high selectivity against anions (Cl(-)) and divalent cations (Ca(2+) and Mg(2+)). This study is the first demonstration and biophysical characterization of channel activity in the venom of A. compressa. The possible functional significance of this channel activity is discussed in light of the unusual nature of the effects of this wasp venom on the behavior of its prey.

Animals↗
PubMed2004

Hunting the Stobbs factor.

Image contrast in transmission electron microscopy is often three or more times less than theory predicts. Recent off-axis holography suggests that the origin of this Stobbs factor may lie in thermal diffuse scattering. In the light of this result, possibilities for further observations by TEM, STEM, CBED and holography are suggested as well as frozen phonon computations that include flexural modes.

Journal Article↗
PubMed2006

Adolescents with wheeze have increased risk of additional health problems. The Young-HUNT study, Norway.

OBJECTIVE: To explore the hypothesis of an association between current wheeze and other health problems in adolescence and to investigate any sex differences. METHODS: N=8817 adolescents aged 13-19 years completed a self-administered questionnaire including questions on health and lifestyle in Norway (1995-1997). RESULTS: All subjective health problems were significantly more prevalent in current wheezers compared to non-wheezers (frequent headache: girls 18% vs. 9%, boys 8% vs. 3%; frequent neck and shoulder pain: girls 10% vs. 5%, boys 6% vs. 2%; frequent joint and muscle pain: girls 6% vs. 2%, boys 6% vs. 2%; and frequent abdominal pain: girls 10% vs. 3%, boys 3% vs.1%). In both sexes, adjusted for covariates, current wheezers had statistically significant increased risk of reporting frequent headache (girls OR=2.0, boys OR=2.9), frequent neck and shoulder pain (girls OR=1.9, boys OR=3.3), frequent joint and muscle pain (girls OR=2.7, boys OR=3.5) and frequent abdominal pain (girls OR=2.7, boys OR=2.0). CONCLUSIONS: Current adolescent wheezers reported more additional health problems compared to non-wheezers. Even if girls reported more symptoms in general, the associations were stronger in boys. The findings are important for the clinical approach to teenage wheezers and should increase doctors' awareness of coexistence of other health complaints in these patients.

Abdominal Pain↗