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At least 865 records · Page 48Linked to original sources
PubMed1999

The nuclear pore complex: from molecular architecture to functional dynamics.

Toward dissecting the molecular composition and architecture of the nuclear pore complex (NPC), over the past 18 months novel nucleoporins and NPC subcomplexes were identified and characterized. The three-dimensional structure of isolated yeast NPCs was determined by electron cryomicroscopy. New specimen preparation and labeling protocols localized a number of nucleoporins and NPC subcomplexes within the three-dimensional architecture of the yeast NPC. Structural changes of native NPCs mediated by physiological effectors such as calcium or ATP were monitored by time-lapse atomic force microscopy, thus revealing a first glimpse of the NPC's functional dynamics.

Animals↗
PubMed2000

Reagentless biosensors based on self-deposited redox polyelectrolyte-oxidoreductases architectures.

Reagentless fructose and alcohol biosensors have been produced with a versatile enzyme immobilisation technique which mimics natural interactions and flexibility of living systems. The electrode architecture is built up on electrostatic interactions by the sequential adsorption of redox polyelectrolytes and redox enzymes giving rise to the efficient transformation of substrate fluxes into electrocatalytic currents. All investigated multilayer structures were self-deposited on 3-mercapto-1-propanesulfonic acid monolayers self-assembled on gold electrodes. Fructose dehydrogenase, horseradish peroxidase (HRP) and the couple HRP-alcohol oxidase were electrochemically connected with a cationic poly[(vinylpyridine)Os(bpy)2Cl] redox polymer (RP) interface in a layer-by-layer self-deposited architecture. The dependence of the distance on the electrochemical response of this interface was also studied showing a clear decrease in the Faradaic current when the distance to the electrode surface was increased. The sensitivities obtained for each biosensor were 19.3, 58.1 and 10.6 mA M(-1) cm(-1) for fructose, H2O2 and methanol, respectively. The sensitivity values can be easily controlled by a rational deposition and manipulation of the charge in the catalytic layers. The electrostatic assembly of the electrochemical interface and the catalytic layers resulted in integrated biochemical systems in which mass transfer diffusion and heterogeneous catalytic and electron transfer steps are efficiently coupled and can be easily manipulated.

Alcohol Oxidoreductases↗
PubMed2000

RNA bulges as architectural and recognition motifs.

RNA bulges constitute versatile structural motifs in the assembly of RNA architectures. Three-dimensional structures of RNA molecules and their complexes reveal the role of bulges in RNA architectures and illustrate the molecular mechanisms by which they confer intramolecular interactions and intermolecular recognition.

Base Sequence↗
PubMedDate not supplied

Backscattered electron imaging: A new method for the study of cardiomyocyte architecture using scanning electron microscopy.

Scanning electron microscopy (SEM) with secondary electron emissions is useful for the study of cardiomyocyte architecture, however, the information is limited from the cell surface. Whereas backscattered electron (BSE) emission can give a high-resolution image of the specimen's intracellular structure after heavy metal staining. In this study, we applied BSE imaging analysis to the study of the arrangement of cardiomyocytes in the myocardium. The tissue specimens from a normal fresh monkey heart, normal human heart obtained at autopsy, and surgically resected tissue from a patient with old myocardial infarction in the left ventricular aneurysmectomy were used. The tissue specimens were fixed in neutral formalin, treated with NaOH and then stained with Gomori's silver methenamine reagent followed by tannic acid and osmium tetroxide. After dehydration and drying, the specimens were coated with carbon and examined by SEM with a BSE detector. In the tissue preparations, the A bands of sarcomeres were selectively stained with silver so that the arrangements of subsarcolemmal myofibrils and the intercalated discs were clearly seen in the BSE images. In the left ventricular aneurysmal walls of old myocardial infarction, atrophied cardiomyocytes with disarray of subsarcolemmal myofibrils were observed. The results strongly suggest that BSE images are further applicable to the study of the architecture of cardiac myocytes and their branches, and the arrangement of intracellular myofibrils in various diseased myocardium.

Animals↗
PubMedDate not supplied

Maintaining squamous epithelial architecture in a human cervical epithelium to SCID mouse xenograft model system.

OBJECTIVE: To establish a mouse model system of human cervical epithelium that maintains the stratified squamous architecture overlying a well-defined basement membrane. METHODS: Normal cervical tissue specimens were obtained from the transformation zone of hysterectomy specimens. Small (2 mm) cubes of tissue containing stroma and epithelium were placed subdermally into severe combined immunodeficient (SCID) mice and harvested between 7 and 45 days. Specimens were examined histologically for the presence of stroma, epithelium, and basement membrane. RESULTS: In 49 xenograft attempts in 24 mice, 35 (71%) were identified microscopically. Of these, 28 (80%) had identifiable epithelium and 20 (57%) formed cysts lined with stratified squamous epithelium. A cuboidal basal layer clearly defined the basement membrane. Proliferation within the cyst epithelium was demonstrated by expression of the Ki67 proliferation marker and the presence of mitotic figures. CONCLUSIONS: A human to mouse xenograft model system is described that maintains, in high yield, stratified squamous epithelium overlying a well-defined basement membrane. Advantages of this model system include the following: (1) The tissue originates from readily available human specimens; (2) A stratified squamous epithelial architecture is maintained for a sufficient time to study viral effects on proliferation; (3) The basement membrane of the epithelium is well defined, allowing for investigation of connective tissue factors in cervical intraepithelial neoplasia and cervical cancer.

Animals↗
PubMed1999

RNA architecture dictates the conformations of a bound peptide.

BACKGROUND: The biological function of several viral and bacteriophage proteins, and their arginine-rich subdomains, involves RNA-mediated interactions. It has been shown recently that bound peptides adopt either beta-hairpin or alpha-helical conformations in viral and phage peptide-RNA complexes. We have compared the structures of the arginine-rich peptide domain of HIV-1 Rev bound to two RNA aptamers to determine whether RNA architecture can dictate the conformations of a bound peptide. RESULTS: The core-binding segment of the HIV-1 Rev peptide class II RNA aptamer complex spans the two-base bulge and hairpin loop of the bound RNA and the carboxy-terminal segment of the bound peptide. The bound peptide is anchored in place by backbone and sidechain intermolecular hydrogen bonding and van der Waals stacking interactions. One of the bulge bases participates in U*(A*U) base triple formation, whereas the other is looped out and flaps over the bound peptide in the complex. The seven-residue hairpin loop is closed by a sheared G*A mismatch pair with several pyrimidines looped out of the hairpin fold. CONCLUSIONS: Our structural studies establish that RNA architecture dictates whether the same HIV-1 Rev peptide folds into an extended or alpha-helical conformation on complex formation. Arginine-rich peptides can therefore adapt distinct secondary folds to complement the tertiary folds of their RNA targets. This contrasts with protein-RNA complexes in which elements of RNA secondary structure adapt to fit within the tertiary folds of their protein targets.

Arginine↗
PubMed2001

Stat3 in thymic epithelial cells is essential for postnatal maintenance of thymic architecture and thymocyte survival.

This study describes abnormalities of the thymus in mice in which the Stat3 gene has been specifically disrupted behind the keratin 5 promoter. In these mice, virtually all of the thymic epithelial cells (TEC) were deficient for Stat3 activation. Adult mutant mice developed severe thymic hypoplasia, which included alterations in the cortical TEC architecture that coincided with the loss of thymocytes. Even during the asymptomatic period of preadolescence, these mice exhibited a higher susceptibility of the thymus to suboptimal doses of dexamethasone or gamma-irradiation, while their thymocytes per se were no more sensitive than controls. These results indicate that Stat3 in TEC plays an essential role in maintaining thymic architecture and thymocyte survival.

Animals↗
PubMed2001

The evolution of plant architecture.

The vascular plants have evolved from a simple body plan that has diversified into the vast array of architectures seen in plants today. Much architectural diversity results from the varied growth patterns of apical and axillary meristems. Current research is showing that meristem growth patterns are regulated genetically and hormonally, and the genes that control these processes are being identified and characterized.

Biological Evolution↗
PubMed2003

The role of nutrient availability in regulating root architecture.

The ability of plants to respond appropriately to nutrient availability is of fundamental importance for their adaptation to the environment. Nutrients such as nitrate, phosphate, sulfate and iron act as signals that can be perceived. These signals trigger molecular mechanisms that modify cell division and cell differentiation processes within the root and have a profound impact on root system architecture. Important developmental processes, such as root-hair formation, primary root growth and lateral root formation, are particularly sensitive to changes in the internal and external concentration of nutrients. The responses of root architecture to nutrients can be modified by plant growth regulators, such as auxins, cytokinins and ethylene, suggesting that the nutritional control of root development may be mediated by changes in hormone synthesis, transport or sensitivity. Recent information points to the existence of nutrient-specific signal transduction pathways that interpret the external and internal concentrations of nutrients to modify root development. Progress in this field has led to the cloning of regulatory genes that play pivotal roles in nutrient-induced changes to root development.

Cell Differentiation↗
PubMed2000

Architecture for networked electronic patient record systems.

There have been two major approaches to the development of networked electronic patient record (EPR) architecture. One uses object-oriented methodologies for constructing the model, which include the GEHR project, Synapses, HL7 RIM and so on. The second approach uses document-oriented methodologies, as applied in examples of HL7 PRA. It is practically beneficial to take the advantages of both approaches and to add solution technologies for network security such as PKI. In recognition of the similarity with electronic commerce, a certificate authority as a trusted third party will be organised for establishing networked EPR system. This paper describes a Japanese functional model that has been developed, and proposes a document-object-oriented architecture, which is-compared with other existing models.

Computer Communication Networks↗
PubMed2001

Building a generic architecture for medical information exchange among healthcare providers.

Due to the inability to exchange clinical information among hospitals, continuity of care cannot be maintained and a tremendous amount of medical resource has been wasted. This paper describes an architecture that would facilitate exchange of clinical information among heterogeneous hospital information systems. It is dubbed 'Medical Information Exchange Center' or MIEC as part of a six-year Health Information Network Project hosted by the Department of Health. MIEC was designed so that it is innovative yet technically feasible today. It is convenient for authorized users yet secure enough so people can trust and has minimal impact to participated hospitals. Authorized users will be able to access information through two web-based interfaces directed to physician and non-physician users respectively. Hospitals are connected through a virtual private network to exchange patient information and users need to obtain a private key from the certificate authority in order to securely connect to MIEC. A pilot project was conducted to demonstrate the feasibility of this architecture and the problems encountered were discussed.

Computer Communication Networks↗
PubMed2001

Estimating motor-unit architectural properties by analyzing motor-unit action potential morphology.

OBJECTIVE: We investigated the architectural organization of groups of neighboring motor units (MUs) in normal brachial biceps and tibialis anterior muscles by analyzing morphological landmarks of their MU action potentials (MUAPs). METHODS: EMG signals containing multiple MUAPs were recorded using a monopolar needle electrode during moderate isometric voluntary contractions. The MUAPs were identified using computer-aided decomposition, and averaged. For each MUAP the onset, spike, terminal wave, and slow afterwave were identified; then the location of the MU's endplate and muscle/tendon junction were estimated from the latencies of the spike and terminal wave with respect to the MUAP onset. RESULTS: The analysis revealed a variety of architectural organizations, including single and multiple endplate zones, MU fractions, pennation, intramuscular aponeuroses, and centrally and non-centrally located endplates. CONCLUSIONS: This type of morphological analysis of the MUAP promises to be informative for studying normal MU properties as well as evaluating MU reorganization in disease.

Action Potentials↗
PubMed2003

A conserved chromatin architecture marks and maintains the restricted germ cell lineage in worms and flies.

In C. elegans, mRNA production is initially repressed in the embryonic germline by a protein unique to C. elegans germ cells, PIE-1. PIE-1 is degraded upon the birth of the germ cell precursors, Z2 and Z3. We have identified a chromatin-based mechanism that succeeds PIE-1 repression in these cells. A subset of nucleosomal histone modifications, methylated lysine 4 on histone H3 (H3meK4) and acetylated lysine 8 on histone H4 (H4acetylK8), are globally lost and the DNA appears more condensed. This coincides with PIE-1 degradation and requires that germline identity is not disrupted. Drosophila pole cell chromatin also lacks H3meK4, indicating that a unique chromatin architecture is a conserved feature of embryonic germ cells. Regulation of the germline-specific chromatin architecture requires functional nanos activity in both organisms. These results indicate that genome-wide repression via a nanos-regulated, germ cell-specific chromatin organization is a conserved feature of germline maintenance during embryogenesis.

Animals↗
PubMed2005

The evolutionary relationship of the domain architectures in the RhoGEF-containing proteins.

Domain insertions and deletions lead to variations in the domain architectures of the proteins from their common ancestor. In this work, we investigated four groups of the RhoGEF-containing proteins from different organisms with domain architectures RhoGEF-PH-SH3, SH3-RhoGEF-PH, RhoGEF-PH, and SH3-RhoGEF defined in the Pfam database. The phylogenetic trees were constructed using each individual domain and/or the combinations of all the domains. The phylogenetic analysis suggests that RhoGEF-PH-SH3 and SH3-RhoGEF-PH might have evolved from RhoGEF-PH through the insertion of SH3 independently, while SH3-RhoGEF of proteins in fruit fly might have evolved from SH3-RhoGEF-PH by the degeneration of PH domain.

Animals↗
PubMed2002

Recovery of proximal tibia bone mineral density and strength, but not cancellous bone architecture, after long-term bisphosphonate or selective estrogen receptor modulator therapy in aged rats.

Various bisphosphonates and the selective estrogen receptor modulator (SERM) raloxifene are approved treatments of postmenopausal osteoporosis. They increase bone mineral density (BMD), decrease bone turnover, and reduce vertebral fracture incidence through different cellular mechanisms. We investigated the bone cellular activities, architecture, mineral content/density, and strength of ovariectomized (ovx) rats on a long-term bisphosphonate or SERM treatment, at doses of either agent correcting bone strength. Eleven weeks postovariectomy, 6-month-old rats were treated with the SERM MDL 103,323 or with the bisphosphonate pamidronate for 5 months. Doses of pamidronate and MDL 103,323 were selected from previous studies showing correction of the ovx-induced decrease of ultimate strength of proximal tibia. Ultimate and yield strengths, BMD, and histomorphometric parameters were all quantified at the same site, i.e., the proximal tibia metaphysis. Long-term pamidronate decreases bone turnover and bone formation activity, leading to trabecular thinning. MDL 103,323 decreases bone turnover to a lesser extent, and slightly protects trabecular architecture by uncoupling bone resorption and formation activities. The yield strength is corrected by pamidronate, but not by MDL 103,323 treatment. However, neither compound restores the ovariectomy-induced cancellous bone loss. Total tissue area and cortical thickness are unchanged with pamidronate or MDL 103,323 treatment, indicating that cortical bone mass, thickness, and cross-sectional area are not modified. The discrepancy between proximal tibia BMD and mechanical resistance to fracture modifications, on the one hand, and cancellous bone volume, on the other hand, could be due to changes in the degree of mineralization of bone matrix and/or of the intrinsic properties of the bone matrix.

Aging↗
PubMed1998

Impact of spatial resolution on the prediction of trabecular architecture parameters.

Although the efficacy of various measures for the assessment of trabecular bone architecture has been widely studied, the impact of spatial resolution on the estimation of these measures has remained relatively unexplored. In this study, ten cubes each of human trabecular bone from the femur and vertebral bodies were obtained from nine cadavers (four males and five females), aged 23-67 years (mean 42.3 years). These specimens were serially milled and imaged at a resolution of 40 microm to produce three-dimensional digitizations from which traditional morphometric and structural anisotropy measures could be computed based on a three-dimensional approach. The cubes were then artificially degraded to an in-plane resolution of 100 microm and an out-of-plane (slice) resolution of 100-1000 microm. These resolutions mimicked in vivo resolutions as seen using magnetic resonance (MR) imaging. All images, original and degraded, were individually segmented using a thresholding algorithm, and both the traditional morphometric and structural anisotropy measures were recomputed. The choice of slice direction was varied along the superior-inferior (axial), anterior-posterior (coronal), and medial-lateral (sagittal) directions to minimize the impact of the lower slice resolution on the architectural measures. It was found that traditional morphometric measures such as trabecular spacing and trabecular number showed weak resolution dependency; measures such as trabecular thickness, however, showed strong resolution dependency and required very high resolutions for precise measurement. In the case of the femur specimens, both structural anisotropy as well as the preferred orientation showed a strong resolution dependency. The resolution dependency of these parameters could be minimized for the femur and the vertebral body specimens if the slice direction was taken along the superior-inferior direction.

Adult↗
PubMed1999

Biomechanical effects of intraspecimen variations in trabecular architecture: a three-dimensional finite element study.

Trabecular architecture is considered important in osteoporosis and has been quantified by a variety of mean parameters characteristic of a whole specimen. Variations within a specimen, however, have been mostly ignored. In this study, the theoretical effects of these intraspecimen variations in architecture on predicted mechanical properties were investigated through a three-dimensional finite element parameter study that simulated variations in trabecular thickness in a controlled manner. An irregularly spaced lattice of different sized rods was used to simulate trabecular bone in three distinct volume fraction ranges, representing young, middle-aged, and elderly vertebral bone. Beta distributions (a type of non-normal distribution) of trabecular thickness with coefficients of variation of either 25%, 40%, or 55% were applied to the rods in each model, and 225 simulations of uniaxial compression tests were performed to obtain modulus values. Percent modulus reductions of 22% and 43% were predicted when the intraspecimen coefficient of variation in trabecular thickness was increased from 25% to 40% and from 25% to 55%, respectively, for models of equal volume fraction. Furthermore, this trend was predicted to be independent of volume fraction. We conclude, therefore, that consideration of the intraspecimen trabecular thickness variation in conjunction with volume fraction may improve the ability to predict trabecular modulus compared with use of volume fraction alone. Further, the model suggests that if age, disease, or drug treatments increase trabecular thickness variation, this may be detrimental to mechanical properties.

Adult↗
PubMed2004

Changes to medial gastrocnemius architecture after surgical intervention in spastic diplegia.

We assessed the architecture of the medial gastrocnemius in nine children (five males, four females; age range 6 to 15 years; mean 10 years 10 months, SD 3 years 6 months) with spastic diplegia by ultrasound imaging before and after a gastrocnemius recession. The children were ambulant (seven independent, one with a posterior walker, one using crutches) before and after surgical intervention. We compared values for fascicle lengths and deep fascicular-aponeurosis angles with those from a group of normally developing children (five males, five females; age range 6 to 11 years; mean 8 years 4 months, SD 1 year 4 months). Despite a variable interval between assessments (from 56 to 610 days), fascicles were shorter (p=0.00226) and the deep fascicular-aponeurosis angle increased (p=0.0152) after intervention. Fascicle lengths of patients were similar to those in the group of normally developing children before surgery. After surgery, fascicles in the group of children with spastic diplegia were shorter than in their normally developing peers (p=0.00109). The gastrocnemius recession procedure alters muscle architecture, though the degree of fascicular shortening varied, with four of the participants in our study losing less than 10% of their original fascicular length at maximum dorsiflexion. Increases in ankle-joint power in walking, observed after surgical intervention in children with spastic diplegia, may be due to a more normal ankle position rather than to improvements in the active mechanical performance of the gastrocnemius.

Adolescent↗