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At least 1,063 records · Page 59Linked to original sources
PubMed2006

Angiogenesis-like activity of endothelial cells co-cultured with VEGF-producing smooth muscle cells.

A number of strategies have been investigated to improve therapeutic vascularization of ischemic and bioengineered tissues. In these studies, we genetically modified vascular smooth muscle cells (VSMC) to promote endothelial cell proliferation, migration, and formation of microvascular networks. VSMCs were virally transduced to produce vascular endothelial growth factor (VEGF), which acts as a chemoattractant and mitogen of endothelial cells (EC). VSMCs transduced with VEGF(165) cDNA produced significant levels of the protein (2-4 ng/10(5) cell/day). The proliferation of ECs increased after exposure to VEGF-transfected SMCs or their conditioned media. The chemotactic response of ECs to the VEGF-producing cells was explored in two in vitro systems, the modified Boyden chamber assay and a 2-D fence-style migration assay, and both demonstrated increased migration of ECs in response to VEGF-transfected cells. Furthermore, endothelial cells seeded on top of the VEGF-transfected SMCs formed capillary-like structures. These results suggest that VSMCs genetically modified to produce VEGF could be a potential delivery mechanism to enhance endothelial cell migration and subsequent capillary formation, which in turn could improve vascularization of ischemic or regenerating tissue. Furthermore, this system could potentially be used as an in vitro test bed for evaluation of novel angiogenic and anti-angiogenic compounds.

Animals↗
PubMed2006

Long-term survival and growth of pulsatile myocardial tissue grafts engineered by the layering of cardiomyocyte sheets.

Recently researchers have attempted to bioengineer three-dimensional (3-D) myocardial tissues using cultured cells in order to repair damaged hearts. In contrast to the conventional approach of seeding cells onto 3-D biodegradable scaffolds, we have explored a novel technology called cell sheet engineering, which layers cell sheets to construct functional tissue grafts. In this study, in vivo survival, function, and morphology of myocardial tissue grafts were examined. Neonatal rat cardiomyocytes were noninvasively harvested as contiguous cell sheets from temperature-responsive culture dishes simply by reducing the culture temperature. Cardiomyocyte sheets were then layered and transplanted into the subcutaneous tissues of athymic rats. The microvasculature of the grafts was rapidly organized within a few days with macroscopic graft beatings observed 3 days after transplantation and preserved up to one year. Size, conduction velocity, and contractile force of transplanted grafts increased in proportion to the host growth. Histological studies showed characteristic structures of heart tissue, including elongated cardiomyocytes, well-differentiated sarcomeres, and gap junctions within the grafts. In conclusion, long-term survival and growth of pulsatile myocardial tissue grafts fabricated by layering cell sheets were confirmed, demonstrating that myocardial tissue regeneration based on cell sheet engineering may prove useful for permanent myocardial tissue repair.

Animals↗
PubMed2006

Review: tissue engineering of the urinary bladder: considering structure-function relationships and the role of mechanotransduction.

A variety of conditions encountered in urology result in bladder dysfunction and the need for bioengineered tissue substitutes. Traditionally, a number of synthetic materials and natural matrices have been used in experimental and clinical settings. However, the production of functional bladder tissue replacements remains elusive. The urinary bladder sustains considerable structural deformation during its normal function and represents an ideal model tissue in which to study the effects of biomechanical simulation on tissue morphogenesis, differentiation, and function. However, the actual role of mechanical forces within the bladder has received little attention. A strategy in which in vitro-generated tissue constructs are conditioned by exposure to the same mechanical forces as they would encounter in vivo could potentially be used both in the development of functional tissue replacements and to further study the role of biomechanical signalling. The purpose of this review is to examine the role and structure-function relationship of the urinary bladder and, through consultation of the literature available on mechanotransduction and tissue engineering of alternative tissues, to determine the factors that need to be considered when biomechanically engineering a functional bladder.

Animals↗
PubMed2004

Insulin-like growth factor I controls adhesion strength mediated by alpha5beta1 integrins in motile carcinoma cells.

One of the intriguing questions regarding cell motility concerns the mechanism that makes stationary cells move. Here, we provide the first physical evidence that the onset of breast cancer cell motility in response to insulin-like growth factor I (IGF-I) correlates with lowering of adhesion strength from 2.52 +/- 0.20 to 1.52 +/- 0.13 microdynes/microm2 in cells attached to fibronectin via alpha5beta1 integrin. The adhesion strength depends on the dose of IGF-I and time of IGF-I treatment. Weakening of cell-matrix adhesion is blocked significantly (p < 0.01) by the catalytically inactive IGF-I receptor (IGF-IR) and the phosphoinositide 3-kinase (PI-3 kinase) inhibitor LY-294002, but it is unaffected by mitogen-activated protein kinase kinase inhibitor UO-126 and Src kinase inhibitor PP2. Sustained blockade of Rho-associated kinase (ROCK) with Y-27632 down-regulates adhesion strength in stationary, but not in IGF-I-treated, cells. Jasplakinolide, a drug that prevents actin filament disassembly, counteracts the effect of IGF-I on integrin-mediated cell adhesion. In the absence of growth factor signaling, ROCK supports a strong adhesion via alpha5beta1 integrin, whereas activation of the IGF-IR kinase reduces cell-matrix adhesion through a PI-3K-dependent, but ROCK-independent, mechanism. We propose that disassembly of the actin filaments via PI-3 kinase pathway contributes to weakening of adhesion strength and induction of cell movement. Understanding how cell adhesion and migration are coordinated has an important application in cancer research, developmental biology, and tissue bioengineering.

Actins↗
PubMed1996

Anticipating public reaction to the use of genetic engineering in infant nutrition.

Public acceptance of new food products will be the major determinant of their commercial success. I present selected findings from two national social science research projects aimed at gauging consumer knowledge of and understanding consumer attitudes about biotechnology, as well as about the specific use of genetic engineering in milk production. People are more willing to accept products if they understand them and are assured by credible sources that such products are safe and effective. Perceived health concerns and ethical issues will be important to many people and are an important challenge to acceptance. Women tend to be more skeptical about these new products than are men. I make recommendations for more-effective educational efforts, based on social science research, that could increase acceptance by key consumer groups and, ultimately, the commercial success of bioengineered food products.

Biotechnology↗
PubMed1996

Whole-body impedance--what does it measure?

Although the bioelectrical impedance technique is widely used in human nutrition and clinical research, an integrated summary of the biophysical and bioelectrical bases of this approach is lacking. We summarize the pertinent electrical phenomena relevant to the application of the impedance technique in vivo and discuss the relations between electrical measurements and biological conductor volumes. Key terms in the derivation of bioelectrical impedance analysis are described and the relation between the electrical properties of tissues and tissue structure is discussed. The relation between the impedance of an object and its geometry, scale, and intrinsic electrical properties is also discussed. Correlations between whole-body impedance measurements and various bioconductor volumes, such as total body water and fat-free mass, are experimentally well established; however, the reason for the success of the impedence technique is much less clear. The bioengineering basis for the technique is critically presented and considerations are proposed that might help to clarify the method and potentially improve its sensitivity.

Body Composition↗
PubMed2006

Sensitivity of rice to ultraviolet-B radiation.

BACKGROUND: Depletion of the stratospheric ozone layer leads to an increase in ultraviolet-B (UVB: 280-320 nm) radiation reaching the earth's surface, and the enhanced solar UVB radiation predicted by atmospheric models will result in reduction of growth and yield of crops in the future. Over the last two decades, extensive studies of the physiological, biochemical and morphological effects of UVB in plants, as well as the mechanisms of UVB resistance, have been carried out. SCOPE: In this review, we describe recent research into the mechanisms of UVB resistance in higher plants, with an emphasis on rice (Oryza sativa), one of the world's most important staple food crops. Recent studies have brought to light the following remarkable findings. UV-absorbing compounds accumulating in the epidermal cell layers have traditionally been considered to function as UV filters, and to play an important role in countering the damaging effects of UVB radiation. Although these compounds are effective in reducing cyclobutane pyrimidine dimer (CPD) induction in plants exposed to a challenge exposure to UVB, certain levels of CPD are maintained constitutively in light conditions containing UVB, regardless of the quantity or presence of visible light. These findings imply that the systems for repairing DNA damage and scavenging reactive oxygen species (ROS) are essential for plants to grow in light conditions containing UVB. CONCLUSION: CPD photolyase activity is a crucial factor determining the differences in UVB sensitivity between rice cultivars. The substitution of one or two bases in the CPD photolyase gene can alter the activity of the enzyme, and the associated resistance of the plant to UVB radiation. These findings open up the possibility, in the near future, of increasing the resistance of rice to UVB radiation, by selective breeding or bioengineering of the genes encoding CPD photolyase.

DNA, Plant↗
PubMed1994

BIOESTIM: software for automatic design of estimators in bioprocess engineering.

This paper describes BIOESTIM, a software package devoted to on-line estimation in bioprocess engineering. BIOESTIM enables bioengineers automatically to design state and parameter estimators from a minimal knowledge of the process kinetics. Such estimators allow development of software sensors capable of coping with the lack of reliable instrumentation suited to real-time monitoring. The estimator building procedure through BIOESTIM starts up from a dynamical material balance model of the bioprocess. This model, supplied by the user, is next completed by other information with no requirement for numerical values: the user has only to specify available measurements, coupled reactions and the known yield coefficients. On the base of this knowledge, BIOESTIM proceeds to symbolic algebraic manipulations on the model in order to study estimation possibilities and check identifiability of yield coefficients. When the design of an estimator is possible, the corresponding equations are automatically generated. Moreover, these estimators are stored in a user-specified file which is automatically interfaced with a specialized simulation software including data treatment and numerical integration packages. Thus, the user can simulate the estimator performances under various operational conditions using available experimental measurements. A typical example dealing with microbial growth and biosynthesis reactions is given in order to illustrate the main functional capabilities of BIOESTIM. BIOESTIM has been designed and written in a modular fashion. The module dealing with estimators design makes use of symbolic computation; it is written in Mathematica and runs on every computer on which this language is available.

Algorithms↗
PubMed2000

Genetic network inference: from co-expression clustering to reverse engineering.

MOTIVATION: Advances in molecular biological, analytical and computational technologies are enabling us to systematically investigate the complex molecular processes underlying biological systems. In particular, using high-throughput gene expression assays, we are able to measure the output of the gene regulatory network. We aim here to review datamining and modeling approaches for conceptualizing and unraveling the functional relationships implicit in these datasets. Clustering of co-expression profiles allows us to infer shared regulatory inputs and functional pathways. We discuss various aspects of clustering, ranging from distance measures to clustering algorithms and multiple-cluster memberships. More advanced analysis aims to infer causal connections between genes directly, i.e. who is regulating whom and how. We discuss several approaches to the problem of reverse engineering of genetic networks, from discrete Boolean networks, to continuous linear and non-linear models. We conclude that the combination of predictive modeling with systematic experimental verification will be required to gain a deeper insight into living organisms, therapeutic targeting and bioengineering.

Animals↗
PubMed1991

CAMBIO: software for modelling and simulation of bioprocesses.

CAMBIO, a software package devoted to bioprocess modelling, which runs on Apollo computers, is described. This software enables bioengineers to easily and interactively design appropriate mathematical models directly from their perception of the process. CAMBIO provides the user with a set of design symbols and mnemonic icons in order to interactively design a functional diagram. This diagram has to exhibit the most relevant components with their related interactions through biological and physico-chemical reactions. Then, CAMBIO automatically generates the dynamical material balance equations of the process in the form of an algebraic-differential system by taking advantage of the knowledge involved in the functional diagram. The model may be used for control design purpose or completed by kinetics expressions with a view to simulation. CAMBIO offers facilities to generate a simulation model (for coding of kinetics, introducing auxiliary variables, etc.). This model is automatically interfaced with a specialized simulation software which allows an immediate visualization of the process dynamical behaviour under various operational conditions (possibly involving feedback control strategies). An example of an application dealing with yeast fermentation is given.

Algorithms↗
PubMed2004

Probabilistic representation of gene regulatory networks.

MOTIVATION: Recent experiments have established unambiguously that biological systems can have significant cell-to-cell variations in gene expression levels even in isogenic populations. Computational approaches to studying gene expression in cellular systems should capture such biological variations for a more realistic representation. RESULTS: In this paper, we present a new fully probabilistic approach to the modeling of gene regulatory networks that allows for fluctuations in the gene expression levels. The new algorithm uses a very simple representation for the genes, and accounts for the repression or induction of the genes and for the biological variations among isogenic populations simultaneously. Because of its simplicity, introduced algorithm is a very promising approach to model large-scale gene regulatory networks. We have tested the new algorithm on the synthetic gene network library bioengineered recently. The good agreement between the computed and the experimental results for this library of networks, and additional tests, demonstrate that the new algorithm is robust and very successful in explaining the experimental data. AVAILABILITY: The simulation software is available upon request. SUPPLEMENTARY INFORMATION: Supplementary material will be made available on the OUP server.

Algorithms↗
PubMed2005

Three-stage prediction of protein beta-sheets by neural networks, alignments and graph algorithms.

MOTIVATION: Protein beta-sheets play a fundamental role in protein structure, function, evolution and bioengineering. Accurate prediction and assembly of protein beta-sheets, however, remains challenging because protein beta-sheets require formation of hydrogen bonds between linearly distant residues. Previous approaches for predicting beta-sheet topological features, such as beta-strand alignments, in general have not exploited the global covariation and constraints characteristic of beta-sheet architectures. RESULTS: We propose a modular approach to the problem of predicting/assembling protein beta-sheets in a chain by integrating both local and global constraints in three steps. The first step uses recursive neural networks to predict pairing probabilities for all pairs of interstrand beta-residues from profile, secondary structure and solvent accessibility information. The second step applies dynamic programming techniques to these probabilities to derive binding pseudoenergies and optimal alignments between all pairs of beta-strands. Finally, the third step uses graph matching algorithms to predict the beta-sheet architecture of the protein by optimizing the global pseudoenergy while enforcing strong global beta-strand pairing constraints. The approach is evaluated using cross-validation methods on a large non-homologous dataset and yields significant improvements over previous methods. AVAILABILITY: http://www.igb.uci.edu/servers/psss.html.

Algorithms↗
PubMed1997

The intubating laryngeal mask. I: Development of a new device for intubation of the trachea.

The standard laryngeal mask airway (LMA) functions both as a ventilatory device and as an aid to blind/fibrescopic-guided tracheal intubation. We describe the radiological and laboratory work used to bioengineer a new laryngeal mask prototype, the intubating laryngeal mask airway (ILMA). The aim was to create a new airway system with better intubation characteristics than the LMA. Other design goals were to eliminate the need for head-neck manipulation and insertion of fingers in the mouth during placement. Development was aided by analysis of magnetic resonance images of the human pharynx and laboratory testing with a variety of tracheal tubes. The principal features of this new system are an anatomically curved, rigid airway tube with an integral guiding handle, an epiglottic elevating bar replacing the mask bars, a guiding ramp built into the floor of the mask aperture and a modified silicone tracheal tube developed for use with the device.

Biomedical Engineering↗
PubMed2026

Deconstructing empirical fitness seascapes across scales of granularity.

The fitness landscape metaphor remains resonant in evolutionary theory and has facilitated the birth of newer concepts, like the fitness seascape, that consider the role of environmental context in shaping the dynamics of evolution. Since its emergence, the seascape has appeared in numerous studies examining how different and fluctuating environments shape evolutionary outcomes. Despite growing interest, we lack comprehensive examinations of how environmental context shapes features of fitness seascapes. In this study, we address this gap by deconstructing empirical fitness seascapes across scales of granularity: loci, locus interactions (epistasis), alleles, trajectories, and entire seascapes. For each, we examine how environmental context influences qualitative and quantitative aspects of seascapes, and find that they change appreciably, with patterns specific to individual systems of study. We also quantify how much each scale varies across environments, and find that certain scales tend to be more sensitive to context than others. In summary, we reflect on the implications of the seascape metaphor for the incorporation of environmental effects into theoretical population genetics, for understanding how the environment shapes evolution in disease systems, and for contemporary bioengineering efforts.

Genetic Fitness↗
PubMed2001

Orthostatic hypotension in elderly persons during passive standing: a comparison with young persons.

BACKGROUND: The present study was aimed at clarifying the mechanism of orthostatic hypotension (OH) that occurs in elderly persons and at investigating assisting methods to prevent OH by evaluating changes in autonomic nervous system (ANS) activity and cerebral circulation of elderly persons when engaged in passive standing. METHODS: Eight elderly volunteers and 9 young volunteers gave informed consent to participate in the study. Two experimental conditions were established: (i) "active standing," in which the subjects stood on their own with guidance from an assistant, and (ii) "passive standing," in which the subjects were placed in a standing position completely by an assistant. ANS was determined before and after standing by measuring the heart rate variability. The reaction of the ANS was evaluated on the basis of low-frequency power (LF: 0.05--0.15 Hz) and high-frequency power (HF: 0.15--0.4 Hz), which were separated from the R-R interval data by power spectral analysis using the fast Fourier transformation. Cerebral perfusion was measured over the right frontal region using a near-infrared spectroscopy cerebral oxygen monitor. RESULTS: The main findings were: (i) Transient decreases in blood pressure occurred immediately after standing in both the young and elderly subjects. (ii) The LF:HF ratio increased significantly ( p <.05) immediately after active standing in the young subjects, whereas this ratio increased in the elderly subjects after some delay. (iii) The LF:HF ratio increased significantly ( p <.01) immediately after passive standing in the young subjects, whereas this ratio decreased significantly ( p <.05) in the elderly subjects. (iv) In the elderly subjects, the total hemoglobin (HbT) and oxyhemoglobin showed the greatest decrease during the 15-second period after standing. The maximum changes in the HbT with passive standing differed significantly ( p <.01) from those observed during active standing. CONCLUSIONS: Our findings emphasize the need to devise bioengineered means that allow elderly persons to exert themselves, to maintain or improve muscle contractility and ANS function, while providing minimum assistance for standing.

Adult↗
PubMed2002

Miniaturization: an overview of biotechnologies for monitoring the physiology and pathophysiology of rodent animal models.

Recent advances in bioengineering technologies have made it possible to collect high-quality reproducible data quantitatively in a wide range of laboratory animal species, including rodents. Several of these technologies are incorporated into a plan called Miniaturization, which aims to design, develop, and maintain rodent animal models to study the pathophysiology and therapy of human diseases. Laser Doppler flowmetry, digital sonomicrometry, bioelectrical impedance, and microdialysis are some of the most widely used methods under the plan because they cause minimal pain and distress, reduce the number of animals used in biomedical research, and allow chronic, nonterminal assessment of physiological parameters in rodents. An overview of each of these technologies and their major applications in rodents used for biomedical research is provided.

Animals↗
PubMed2002

Transgenic rice is a source of iron for iron-depleted rats.

Iron deficiency is one of the most prevalent nutrient deficiencies in the world. A sustainable solution to dietary iron deficiency may be achieved in part by increasing bioavailable iron in seeds used for foods such as rice. Because ferritin is used as a natural source of iron in the early development of humans, other animals and plants, the bioavailability of iron in rice seeds, provided in amounts equal to ferrous sulfate, and in transgenic rice with ferritin was tested in iron-deficient rats. A standard hemoglobin (Hb) repletion bioassay was used with rats made anemic followed by complete diets containing equivalent amounts of iron as FeSO(4) or one of three different bioengineered rice varieties (Kitaake and two transgenic derivatives with ferritin targeted to the seed, FK11 and FK22). Rice diets were as effective as the FeSO(4) diet in replenishing hematocrit, Hb concentration and liver iron concentrations. These data suggest that Mendelian and biotechnological approaches to manipulating ferritin expression of seed iron in rice may contribute to a sustainable solution to global problems of iron deficiency.

Anemia, Iron-Deficiency↗
PubMed2002

Isolation and characterization of the CYP71D16 trichome-specific promoter from Nicotiana tabacum L.

Trichomes are specialized epidermal cells that produce secretions that are thought to provide a first line of defence against pests and pathogens. Many trichome-secreted compounds are used commercially as flavourings, medicines, etc. Described here is the cloning and characterization of the promoter of a tobacco trichome-specific P450 gene, CYP71D16. This promoter is shown to direct the specific expression of the reporter gene, beta-glucuronidase (GUS), in glandular trichomes of Nicotiana tabacum cv. T.I. 1068 at all developmental stages. With the full promoter, GUS activity was predominantly in the gland cell, with less in the stalk cell adjacent to the gland, and in lower stalk cells. GUS staining was also observed in the most distal trichome stalk cells of non-glandular trichomes found on variety T.I. 1112. Promoter deletion analysis revealed that the region from -223 to +111 bp is sufficient to direct trichome-specific expression, but not strong gland expression. Examination of the literature suggests that this is the first characterized trichome-specific-promoter shown to function at all stages of plant development. This promoter may provide efficient bioengineering to enhance pest and pathogen resistance, and for molecular farming based on the trichome gland system.

Base Sequence↗