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At least 1,585 records · Page 88Linked to original sources
PubMed2005

Isotropic proton-detected local-field nuclear magnetic resonance in solids.

A nuclear magnetic resonance method is presented which produces linear, isotropic proton-detected local-field spectra for INS spin systems in powdered samples. The method, heteronuclear isotropic evolution (HETIE), refocuses the anisotropic portion of the heteronuclear dipolar coupling frequencies by evolving the system under a series of specially designed Hamiltonians and evolution pathways. The theory behind HETIE is presented along with experimental studies conducted on a powdered sample of ferrocene, demonstrating the methodology outlined in this paper. Applications of HETIE for use in structure determination in the solid state are discussed.

Journal Article↗
PubMed2004

Engineering biological structures of prescribed shape using self-assembling multicellular systems.

Self-assembly is a fundamental process that drives structural organization in both inanimate and living systems. It is in the course of self-assembly of cells and tissues in early development that the organism and its parts eventually acquire their final shape. Even though developmental patterning through self-assembly is under strict genetic control it is clear that ultimately it is physical mechanisms that bring about the complex structures. Here we show, both experimentally and by using computer simulations, how tissue liquidity can be used to build tissue constructs of prescribed geometry in vitro. Spherical aggregates containing many thousands of cells, which form because of tissue liquidity, were implanted contiguously into biocompatible hydrogels in circular geometry. Depending on the properties of the gel, upon incubation, the aggregates either fused into a toroidal 3D structure or their constituent cells dispersed into the surrounding matrix. The model simulations, which reproduced the experimentally observed shapes, indicate that the control parameter of structure evolution is the aggregate-gel interfacial tension. The model-based analysis also revealed that the observed toroidal structure represents a metastable state of the cellular system, whose lifetime depends on the magnitude of cell-cell and cell-matrix interactions. Thus, these constructs can be made long-lived. We suggest that spherical aggregates composed of organ-specific cells may be used as "bio-ink" in the evolving technology of organ printing.

Animals↗
PubMed2005

Fibrinogen and fibronectin binding cooperate for valve infection and invasion in Staphylococcus aureus experimental endocarditis.

The expression of Staphylococcus aureus adhesins in Lactococcus lactis identified clumping factor A (ClfA) and fibronectin-binding protein A (FnBPA) as critical for valve colonization in rats with experimental endocarditis. This study further analyzed their role in disease evolution. Infected animals were followed for 3 d. ClfA-positive lactococci successfully colonized damaged valves, but were spontaneously eradicated over 48 h. In contrast, FnBPA-positive lactococci progressively increased bacterial titers in vegetations and spleens. At imaging, ClfA-positive lactococci were restricted to the vegetations, whereas FnBPA-positive lactococci also invaded the adjacent endothelium. This reflected the capacity of FnBPA to trigger cell internalization in vitro. Because FnBPA carries both fibrinogen- and fibronectin-binding domains, we tested the role of these functionalities by deleting the fibrinogen-binding domain of FnBPA and supplementing it with the fibrinogen-binding domain of ClfA in cis or in trans. Deletion of the fibrinogen-binding domain of FnBPA did not alter fibronectin binding and cell internalization in vitro. However, it totally abrogated valve infectivity in vivo. This ability was restored in cis by inserting the fibrinogen-binding domain of ClfA into truncated FnBPA, and in trans by coexpressing full-length ClfA and truncated FnBPA on two separate plasmids. Thus, fibrinogen and fibronectin binding could cooperate for S. aureus valve colonization and endothelial invasion in vivo.

Adhesins, Bacterial↗
PubMed2003

The evolution of warning signals as reliable indicators of prey defense.

It is widely argued that defended prey have tended to evolve conspicuous traits because predators more readily learn to avoid defended prey when they are conspicuous. However, a rival theory proposes that defended prey have evolved such characters because it allows them to be distinguished from undefended prey. Here we investigated how the attributes of defended (unprofitable) and undefended (profitable) computer-generated prey species tended to evolve when they were subject to selection by foraging humans. When cryptic forms of defended and undefended species were similar in appearance but their conspicuous forms were not, defended prey became conspicuous while undefended prey remained cryptic. Indeed, in all of our experiments, defended prey invariably evolved any trait that enabled them to be distinguished from undefended prey, even if such traits were cryptic. When conspicuous mutants of defended prey were extremely rare, they frequently overcame their initial disadvantage by chance. When Batesian mimicry of defended species was possible, defended prey evolved unique traits or characteristics that would make undefended prey vulnerable. Overall, our work supports the contention that warning signals are selected for their reliability as indicators of defense rather than to capitalize on any inherent educational biases of predators.

Animals↗
PubMed2005

Nevogenesis--new thoughts regarding a classical problem.

The development of melanocytic nevi is a multifactorial and heterogeneous biologic process that involves prenatal and postnatal steps. As a consequence, there are two main perspectives to nevi: that of a hamartoma and that of a benign tumor. In this review, dermatopathological studies on congenital and acquired nevi, including studies on age-related and location-dependent changes, are analyzed. These studies have lead to different hypothetical concepts on the evolution of individual lesions. In the light of findings from experimental embryology and stem cell biology, we discuss the histogenesis of nevi with special reference to the temporospatial sequence of melanocyte-basement membrane interactions and hair follicle genesis. Regarding the mechanisms of postnatal nevus development, epidemiological studies demonstrate the importance of constitutional and environmental influences, especially ultraviolet light. Possible molecular pathways of solar nevogenesis involve ultraviolet-induced alterations of the cellular microenvironment (eg, changes in the expression of cytokines and melanocyte adhesion molecules). Recent results and future directions of clinical and experimental research are presented.

Adolescent↗
PubMed2004

Hybrid Monte Carlo-molecular dynamics algorithm for the study of islands and step edges on semiconductor surfaces: application to Si/Si (001).

A classical, hybrid Monte Carlo-molecular dynamic (MC-MD) algorithm is introduced for the study of phenomena like two-dimensional (2D) island stability or step-edge evolution on semiconductor surfaces. This method presents the advantages of working off lattice and utilizing bulk-fitted potentials. It is based on the introduction of collective moves, such as dimer jumps, in the MC algorithm. MD-driven local relaxations are considered as trial moves for the MC. The algorithm is applied to the analysis of 2D Si islands on Si(001). Results on early stages of island formation, island stability versus temperature and system size, and step-edge evolution are presented. In all cases good qualitative agreement with experimental results is found.

Journal Article↗
PubMed2006

Test of thermal transport models through dynamic overpressure stabilization of ablation-front perturbation growth in laser-driven CH foils.

Heat-flow-induced dynamic overpressure at the perturbed ablation front of an inertial confinement fusion target can stabilize the ablative Richtmyer-Meshkov-like instability and mitigate the subsequent ablative Rayleigh-Taylor (RT) instability. A series of experiments was performed on the OMEGA laser to quantify the dynamic overpressure stabilization during the shock transit. Analysis of the experimental data using hydrocode simulations shows that the observed oscillatory evolution of the ablation-front perturbations depends on Dc, the size of the thermal conduction zone, and the fluid velocity in the blowoff region Vb1 that are sensitive to the thermal transport model used. We show that the simulations match the experiment well when the time dependence of the heat-flux inhibition is taken into account using a recently developed nonlocal heat-transport model [V. N. Goncharov et al., Phys. Plasmas 13, 012702 (2006)].

Journal Article↗
PubMed2005

Comprehensive pharmacokinetic model of insulin Glargine and other insulin formulations.

In this paper, a comprehensive pharmacokinetic model for different insulin formulations including insulin Glargine is developed based on the model proposed by Trajanoski et al. (1993). Current models show limitations for insulin Glargine due to the appearance of an uncharacteristic peak in the concentration-time evolution of plasma insulin that does not coincide with real experimental data. This important limitation has been solved in this paper by introducing a new virtual insulin state called the bound state, in addition to the dimeric and hexameric ones. Trying to describe the retarded action of insulin Glargine, the modeling idea behind this approach is that immediately after the subcutaneous injection all the insulin resides in the bound state, and only then small amounts of insulin in the hexameric form disengage from the bound state. For the model evaluation different simulation results are compared. Using experimental data published by Lepore et al. (2000), the developed model turned out to be capable of at least qualitatively predicting the concentration-time profile of plasma insulin. Both exogenous insulin flow simulations and spatial diffusion simulations show the plausibility and correct implementation of the derived model. Considering all these simulation results, the here presented new pharmacokinetic model demonstrates to be able to reproduce real patient behavior simulating even complete insulin regimes including long-acting, intermediate and short-acting insulin formulations.

Computer Simulation↗
PubMed2000

Cytogenetic proof that the brine shrimp Artemia franciscana (Crustacea, Branchiopoda) is found in Argentina.

Artemia brine shrimps are commercially important and they have been extensively studied. This branchiopod crustacean is extensively used in aquaculture and other commercial and applied practices. The genus also awakes an increasing interest worldwide as an experimental model in other basic areas of research such as evolution and cytogenetics. In the present work adult male meiosis and nauplii mitotic cells in two Artemia populations from Argentina (Mar Chiquita and Las Tunas, Córdoba Province) are analyzed and compared to the reference strains A. franciscana (Great Salt Lake, Utah, USA) and A. persimilis (Salinas Grandes de Hidalgo, La Pampa Province, Argentina). The Mar Chiquita population shows the diploid and haploid numbers characteristic of A. franciscana, and a regular male meiosis. In the Las Tunas population diverse diploid and haploid numbers are encountered, and an irregular meiosis is observed in some individuals. Fluorescent DAPI and CMA banding shows bright chromocenters of intermediate size and number in both populations. Cytogenetic and phenotypic data show that the population of Mar Chiquita could be assigned to A. franciscana; the variation found in chromocenter size and number reflects an heterochromatin polytypism already observed in this species. The cytogenetic and morphological traits in Las Tunas population suggest an occasional hybridization between A. franciscana and A. persimilis.

Animals↗
PubMed2003

Evolutionary pressure of a receptor competitor selects different subgroup a avian leukosis virus escape variants with altered receptor interactions.

A complex interaction between the retroviral envelope glycoproteins and a specific cell surface protein initiates viral entry into cells. The avian leukosis-sarcoma virus (ALV) group of retroviruses provides a useful experimental system for studying the retroviral entry process and the evolution of receptor usage. In this study, we demonstrate that evolutionary pressure on subgroup A ALV [ALV(A)] entry exerted by the presence of a competitive inhibitor, a soluble form of the ALV(A) Tva receptor linked to a mouse immunoglobulin G tag (quail sTva-mIgG), can select different populations of escape variants. This escape population contained three abundant ALV(A) variant viruses, all with mutations in the surface glycoprotein hypervariable regions: a previously identified variant containing the Y142N mutation in the hr1 region; a new variant with two mutations, W141G in hr1 and K261E in vr3; and another new variant with two mutations, W145R in hr1 and K261E. The W141G K261E and W145R K261E viruses escape primarily by lowering their binding affinities for the quail Tva receptor competitive inhibitor while retaining wild-type levels of binding affinity for the chicken Tva receptor. A secondary phenotype of the new variants was an alteration in receptor interference patterns from that of wild-type ALV(A), indicating that the mutant glycoproteins are possibly interacting with other cellular proteins. One result of these altered interactions was that the variants caused a transient period of cytotoxicity. We could also directly demonstrate that the W141G K261E variant glycoproteins bound significant levels of a soluble form of the Tvb(S3) ALV receptor in a binding assay. Alterations in the normally extreme specificity of the ALV(A) glycoproteins for Tva may represent an evolutionary first step toward expanding viral receptor usage in response to inefficient viral entry.

Amino Acid Sequence↗
PubMed1999

Methylation pharmacogenetics: catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase.

Methyl conjugation is an important pathway in the biotransformation of many exogenous and endogenous compounds. Pharmacogenetic studies of methyltransferase enzymes have resulted in the identification and characterization of functionally important common genetic polymorphisms for catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase. In recent years, characterization of these genetic polymorphisms has been extended to include the cloning of cDNAs and genes, as well as a determination of the molecular basis for the effects of inheritance on these methyltransferase enzymes. The thiopurine methyltransferase genetic polymorphism is responsible for clinically significant individual variations in the toxicity and therapeutic efficacy of thiopurine drugs such as 6-mercaptopurine. Phenotyping for the thiopurine methyltransferase genetic polymorphism represents one of the first examples in which testing for a pharmacogenetic variant has entered standard clinical practice. The full functional implications of pharmacogenetic variation in the activities of catechol O-methyltransferase and histamine N-methyltransferase remain to be determined. Finally, experimental strategies used to study methylation pharmacogenetics illustrate the rapid evolution of biochemical, pharmacologic, molecular, and genomic approaches that have been used to determine the role of inheritance in variation in drug metabolism, effect, and toxicity.

Animals↗
PubMed1998

Evolution of chronic nitric oxide inhibition hypertension: relationship to renal function.

We conducted longitudinal measurements of blood pressure and renal function in the conscious, chronically catheterized rat before and during acute nitric oxide synthase inhibition (N-nitro-L-arginine methylester [L-NAME], 37 micromol/kg IV) and then chronic administration of oral L-NAME (approximately 37 micromol/kg per 24 hours). These studies specifically investigate the impact on plasma and renal renin as well as volume status during the evolution of this hypertension in rats not subjected to acute experimental stress. Blood pressure progressively increased with chronic administration of L-NAME and reached values greatly above those seen with acute administration of L-NAME. There were parallel increases in renal vascular resistance and development of proteinuria, and glomerular filtration rate began to decline at day 21, coincident with the appearance of renal damage. Twenty-four-hour urinary nitrite and nitrate excretion remained depressed, reflecting reduced nitric oxide synthesis. The plasma renin activity was variable and only increased transiently at 21 days, thus the angiotensin II dependence of this hypertension is not caused by stimulated plasma renin activity. Despite severe hypertension, sodium intake and excretion were unchanged over the 21 days of L-NAME administration. Plasma volume was significantly reduced at days 2 and 12 of L-NAME administration; thus the prolonged plasma volume contraction must result from the acute natriuretic response to the initial acute L-NAME administration.

Animals↗
PubMed2003

Quantitative analysis of vitamin A degradation by Raman spectroscopy.

Vitamin A is known to support cell growth promotion, maintenance, and differentiation of epithelial tissues. Retinol is currently used in cosmetic formulations and products to deliver these and other benefits to the skin. However, retinol is known to be unstable and, therefore, remains of great concern to the cosmetic industry. The decomposition pathways of the retinoids in general have been previously postulated and investigated mostly by high-performance liquid chromatography (HPLC) with UV/Vis spectroscopy. In our studies, we examined specific conditions at which retinol degrades and subsequently identified and quantified the products of retinol decomposition by Raman spectroscopy. We reveal which experimental settings and computational tools allow monitoring of in situ evolution of an all-trans retinol solution when submitted to UV light in the presence of oxygen.

2-Propanol↗
PubMed2006

Deformations in actin comets from rocketing beads.

The mechanical and dynamical properties of the actin network are essential for many cellular processes like motility or division, and there is a growing body of evidence that they are also important for adhesion and trafficking. The leading edge of migrating cells is pushed out by the polymerization of actin networks, a process orchestrated by cross-linkers and other actin-binding proteins. In vitro physical characterizations show that these same proteins control the elastic properties of actin gels. Here we use a biomimetic system of Listeria monocytogenes, beads coated with an activator of actin polymerization, to assess the role of various actin-binding proteins in propulsion. We find that the properties of actin-based movement are clearly affected by the presence of cross-linkers. By monitoring the evolution of marked parts of the comet, we provide direct experimental evidence that the actin gel continuously undergoes deformations during the growth of the comet. Depending on the protein composition in the motility medium, deformations arise from either gel elasticity or monomer diffusion through the actin comet. Our findings demonstrate that actin-based movement is governed by the mechanical properties of the actin network, which are fine-tuned by proteins involved in actin dynamics and assembly.

Actin-Related Protein 2-3 Complex↗
PubMedDate not supplied

Evaluation of spleen cell population and effect of splenectomy on granuloma modulation in BALB/c mice infected with Schistosoma mansoni.

A kinetic study of the cells present in the spleen of BALB/c mice infected with Schistosoma mansoni was carried out. The lymphocytes were evaluated phenotypically with monoclonal antibodies and the effect of splenectomy on the modulation of periovular granuloma was also investigated. The infected mice had proportional increases in the numbers of neutrophils, plasma cells, macrophages and eosinophils in the spleen. The largest number of neutrophil, plasma cells and macrophage were found between the 8th and the 12th week of infection, while the amount of eosinophils were higher later on, around the 20th week. The lymphocytes phenotypically characterized as Thy 1.2, Lyt 1.2 (CD4) increased mildly in proportional numbers. However, the percentage of lymphocytes with the Lyt 2.2 (CD8) phenotype, which is characteristic of suppressor and cytotoxic T cells, increased significantly with the progress of the disease. The numbers of B lymphocytes, which comprise 50% of the mononuclear cells present in the spleen, increased significantly till the 16th week when they began to decrease. The mean diameters of periovular granulomas were comparatively similar in both experimental groups (splenectomized and non-splenectomized mice). However, the evolutive types of granuloma (exudative, intermediate and fibrous) in splenectomized mice were proportionally different from those of non splenectomized mice in the 16th and 24th week of infection. It is inferred that lymphnodes or other secondary lymphoid organs, in the absence of the spleen, assume a modulating action on periovular granulomas, although the evolution of the granulomas is somehow delayed in splenectomized mice.

Animals↗
PubMed2002

Healing response in elastase-induced rabbit aneurysms after embolization with a new platinum coil system.

BACKGROUND AND PURPOSE: Elastase-induced rabbit aneurysms offer promise in preclinical testing, but their radiographic and histologic features after dense packing with platinum coils are unknown. We evaluated these features by using a new platinum coil system. METHODS: Right common carotid arterial (CCA) aneurysms were created in 17 rabbits by distal ligation and intraluminal elastase incubation. At least 3 weeks later, aneurysms were packed with detachable platinum coils. Animals were sacrificed at 2 (group 1, n=4), 4 (group 2, n=5), 12 (group 3, n=4), or 24 (group 4, n=4) weeks. Aneurysmal occlusion and coil compaction were angiographically assessed. Histologic features of tissue covering the coils and the aneurysmal dome were assessed and semiquantitatively compared across groups. RESULTS: No notable tracking, deployment, or detachment problems occurred. Volumetric occlusion was 5-49% (mean, 26.8% +/- 11%). Angiographic occlusion was 100% in six cases, 95% in four, and 90% in seven; occlusion scores remained unchanged in 13 cases, decreased in one, and increased in two (one case excluded from angiographic follow-up). Histologic findings were concordant within groups. Group 1 had coverage with thin fibrin layers and scattered leukocytes; group 2, some spindle-cell coverage; group 3, spindle-cell coverage. In groups 1 and 2, dome findings included only unorganized blood products. In group 3, blood products had been replaced with a hypocellular, poorly staining matrix. Some group 4 subjects had variably aged blood products, with tissue of limited organization. CONCLUSION: The platinum coil system performed well in experimental aneurysmal embolization. Densely packed rabbit aneurysms demonstrate reproducible histologic evolution: early fibrin coverage, delayed spindle-cell coverage, delayed intraaneurysmal thrombus resorption, and occasional coil compaction.

Animals↗
PubMed2005

"You can't make a monkey out of us": Galen and genetics versus Darwin.

The views on the biological relationship between human and ape are polarized. One end is summarized by the axiom that "man is the third chimpanzee", a thesis put forward in an indirect way initially by Charles Darwin in the 19th century. The other is a very modern concept that although similar, the human and ape genomes are distinctly different. We have compared these two views on the subject with the stance of the ancient medical writer Galen. There is a striking resemblance between current and ancient opinion on three key issues. Firstly, on the fact that man and apes are similar but not identical. Secondly, on the influence of such debates on fields much wider than biology. And finally, on the comparative usefulness of apes as a substitute for human anatomy and physiology studies.

Animal Experimentation↗