SEARCH · PubMed Health

Results for “Unique interface”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources

PubMed2005

Waveguide excitation fluorescence microscopy: a new tool for sensing and imaging the biointerface.

A novel biosensing and imaging technique, the waveguide excitation fluorescence microscope, has been developed for the dynamic and quantitative investigation of bio-interfacial events in situ, ranging from ligand-receptor binding to focal adhesion formation in cell-surface interactions. The technique makes use of the evanescent field created when light travels in a mono-mode, planar optical waveguide to excite fluorescence in the near interface region. Advantages of the technique include high target sensitivity for fluorescence detection (femtomolar range), high surface specificity (ca. 100 nm perpendicular to the waveguide), large area analysis with submicron resolution, 'built-in' calibration of fluorescent light gain, and the capability to perform multi-colour imaging in situ and in real time. In this work, the sensitivity of the system has already been demonstrated through dynamic measurements of the streptavidin-biotin binding event to below 20 pM concentrations, signal to noise comparisons with conventional fluorescence microscopy have shown more than a 10-fold improvement, and surface specificity of the technique has also been illustrated in a comparison of fibroblast focal adhesion images. Thus, this new tool can be used to illuminate processes occurring at the interface between biology and synthetic surfaces in a unique manner.

Biosensing Techniques↗

PubMed2004

Role of activin A as a mediator of in vitro endometrial stromal cell decidualization via the cyclic adenosine monophosphate pathway.

OBJECTIVE: To elucidate the regulation and role of activin A in endometrial stromal decidualization. DESIGN: In vitro model of human stromal cell decidualization with cyclic adenosine monophosphate (cAMP) used to evaluate expression of activin A and to evaluate the effect of the addition of follistatin, a known activin inhibitor, on expression of the decidualized phenotype (as measured by levels of insulin-like growth factor binding protein-1 [IGFBP-1]). SETTING: Academic research environment. PATIENT(S): Four premenopausal, normally cycling subjects (age range: 32-40 years). INTERVENTION(S): Endometrial samples were obtained from the subjects after informed consent was obtained. Endometrial stromal cells were treated with cAMP (decidualizing stimulus) and 50 ng/mL, 100 ng/mL, and 200 ng/mL of follistatin for 48 hours. MAIN OUTCOME MEASURE(S): Levels of IGFBP-1 secreted from cells decidualized in the absence and presence of three different concentrations of follistatin. RESULT(S): Addition of follistatin, a known binding protein inhibitor of activin A, resulted in a dose-dependent inhibition of IGFBP-1 secreted into conditioned medium, with the greatest decrease observed at 4 days of decidualization. Cells treated with cAMP and 50 ng/mL, 100 ng/mL, and 200 ng/mL of follistatin demonstrated 67.3%, 58.6%, and 35.5%, respectively, of the IGFBP-1 levels observed with cAMP but without follistatin. CONCLUSION(S): These data suggest that activin A is a necessary component of the cAMP pathway leading to endometrial stromal decidualization. The role of activin A in regulating endometrial stromal decidualization and its known promotion of the invasive phenotype of the trophoblast suggest unique autocrine and paracrine interactions at the maternal/fetal interface during implantation, which might have important clinical implications for the understanding and treatment of fertility and pregnancy disorders.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2004

Molecular mechanisms for viral mimicry of a human cytokine: activation of gp130 by HHV-8 interleukin-6.

Kaposi's sarcoma-associated herpesvirus (KSHV, or HHV-8) encodes a pathogenic viral homologue of human interleukin-6 (IL-6). In contrast to human IL-6 (hIL-6), viral IL-6 (vIL-6) binds directly to, and activates, the shared human cytokine signaling receptor gp130 without the requirement for pre-complexation to a specific alpha-receptor. Here, we dissect the biochemical and functional basis of vIL-6 mimicry of hIL-6. We find that, in addition to the "alpha-receptor-independent" tetrameric vIL-6/gp130 complex, the viral cytokine can engage the human alpha-receptor (IL-6Ralpha) to form a hexameric vIL-6/IL-6Ralpha/gp130 complex with enhanced signaling potency. In contrast to the assembly sequence of the hIL-6 hexamer, the preformed vIL-6/gp130 tetramer can be decorated with IL-6Ralpha, post facto, in a "vIL-6-dependent" fashion. A detailed comparison of the viral and human cytokine/gp130 interfaces indicates that vIL-6 has evolved a unique molecular strategy to interact with gp130, as revealed by an almost entirely divergent structural makeup of its receptor binding sites. Viral IL-6 appears to utilize an elegant combination of both convergent, and unexpectedly divergent, molecular strategies to oligomerize gp130 and activate similar downstream signaling cascades as its human counterpart.

Amino Acid Sequence↗

PubMed2006

IL-3, IL-5, and GM-CSF signaling: crystal structure of the human beta-common receptor.

The cytokines, interleukin-3 (IL-3), interleukin-5 (IL-5), and granulocyte-macrophage colony stimulating factor (GM-CSF), are polypeptide growth factors that exhibit overlapping activities in the regulation of hematopoietic cells. They appear to be primarily involved in inducible hematopoiesis in response to infections and are involved in the pathogenesis of allergic and inflammatory diseases and possibly in leukemia. The X-ray structure of the beta common (betac) receptor ectodomain has given new insights into the structural biology of signaling by IL-3, IL-5, and GM-CSF. This receptor is shared between the three ligands and functions together with three ligand-specific alpha-subunits. The structure shows betac is an intertwined homodimer in which each chain contains four domains with approximate fibronectin type-III topology. The two betac-subunits that compose the homodimer are interlocked by virtue of the swapping of beta-strands between domain 1 of one subunit and domain 3 of the other subunit. Site-directed mutagenesis has shown that the interface between domains 1 and 4 in this unique structure forms the functional epitope. This epitope is similar to those of other members of the cytokine class I receptor family but is novel in that it is formed by two different receptor chains. The chapter also reviews knowledge on the closely related mouse beta(IL-3) receptor and on the alpha-subunit-ligand interactions. The knowledge on the two beta receptors is placed in context with advances in understanding of the structural biology of other members of the cytokine class I receptor family.

Animals↗

PubMed2000

Activation of urocortin transport into brain by leptin.

There are several transport systems for peptides and polypeptides at the blood-brain barrier (BBB) which facilitate the passage of bioactive substances from blood to brain or from brain to blood. Nonetheless, it would be a novel concept for one peptide or polypeptide to activate the transport of another peptide with a similar function but unrelated structure. In this study, we report the first observation of such a phenomenon: activation of a urocortin transport system at the BBB by leptin. Urocortin, a corticotropin-releasing factor (CRF)-related neuropeptide, is a more potent suppressor of food intake than leptin or CRF when injected peripherally. Radiolabeled urocortin ((125)I-urocortin) was used for these in vivo studies in mice; it remained stable and intact during the experimental period. Unlike CRF, urocortin was not saturably transported out of the brain. There was no substantial entry of (125)I-urocortin into brain as determined by sensitive multiple-time regression analysis after iv bolus injection. Addition of leptin, however, caused a dose-related increase in the influx of (125)I-urocortin and greatly facilitated its entry into brain parenchyma; this effect disappeared at higher doses of leptin. Moreover, in the presence of an activating dose of leptin, the entry of (125)I-urocortin into brain was saturable. The results indicate that the presence of leptin contributes to the potent satiety effects of urocortin after peripheral administration. Thus, the action of leptin in the periphery extends beyond its direct passage across the BBB and involves acute modulation of an inert transport system. We believe that these findings have broad physiological implications and indicate a unique function of the BBB as a regulatory interface.

Animals↗

PubMed2006

Modification of rice starch by selective degradation of amylose using alkalophilic Bacillus cyclomaltodextrinase.

A cyclomaltodextrinase (CDase) isolated from alkalophilic Bacillus sp. I-5 (CDase I-5) exists in a dodecameric form, an assembly of six dimers, each catalytic site of which is located in a narrow groove at the interface of the dimeric unit. Because of the unique geometric shape of the catalytic site, the enzyme has the ability to discriminate the molecular size of substrates. An analysis of the hydrolysis reaction of the enzyme revealed that its kcat/Km value on amylose was 14.6 s(-1) (mg/mL)(-1), whereas that for amylopectin was 0.92 s(-1) (mg/mL)(-1), showing an exceptionally high preference toward amylose. CDase I-5 was applied to modify the starch structure to produce low-amylose starch products by incubating rice starch with this enzyme. We found that the amylose content of rice starch decreased from 28.5 to 9%, while the amylopectin content remained almost constant with no significant change in the side chain length distribution. When the CDase I-5-treated rice starch was stored at 4 degrees C for 7 days, the retrogradation rate was significantly retarded as compared to that in the control sample.

Amylopectin↗

PubMed2026

PubMind: literature-based genetic variant extraction and functional annotation using large language models.

Biomedical literature contains extensive functional knowledge on genetic variants, but much remains inaccessible in unstructured text. Existing resources such as ClinVar and HGMD remain limited by coverage, submission bias, update frequency, and sparse annotation. We develop PubMind, an artificial intelligence (AI) framework that uses large language models (LLMs) to triage and extract variant-function-disease associations and supporting evidence from biomedical text. PubMind captures single-nucleotide, copy-number, structural, and gene-fusion variants, and normalizes records to genomic and transcriptomic coordinates. Benchmarking shows >90% accuracy for variant recognition and 99% precision for disease extraction. Applied to >41 million PubMed abstracts and >5 million full-text articles, PubMind generates PubMind-DB, a database of ~1.3 million unique variants with contextual annotations, accessible via web interface and API. Only ~10% of PubMind variants overlap with ClinVar, and >80% of them show concordant pathogenicity labels. PubMind transforms unstructured biomedical text into structured genomic knowledge, advancing variant interpretation for precision medicine.

Large Language Models↗

PubMed1999

Crystal structures of adenine phosphoribosyltransferase from Leishmania donovani.

The enzyme adenine phosphoribosyltransferase (APRT) functions to salvage adenine by converting it to adenosine-5-monophosphate (AMP). APRT deficiency in humans is a well characterized inborn error of metabolism, and APRT may contribute to the indispensable nutritional role of purine salvage in protozoan parasites, all of which lack de novo purine biosynthesis. We determined crystal structures for APRT from Leishmania donovani in complex with the substrate adenine, the product AMP, and sulfate and citrate ions that appear to mimic the binding of phosphate moieties. Overall, these structures are very similar to each other, although the adenine and AMP complexes show different patterns of hydrogen-bonding to the base, and the active site pocket opens slightly to accommodate the larger AMP ligand. Whereas AMP adopts a single conformation, adenine binds in two mutually exclusive orientations: one orientation providing adenine-specific hydrogen bonds and the other apparently positioning adenine for the enzymatic reaction. The core of APRT is similar to that of other phosphoribosyltransferases, although the adenine-binding domain is quite different. A C-terminal extension, unique to Leishmania APRTs, extends an extensive dimer interface by wrapping around the partner molecule. The active site involves residues from both subunits of the dimer, indicating that dimerization is essential for catalysis.

Adenine↗

PubMed2004

NRPS-PKS: a knowledge-based resource for analysis of NRPS/PKS megasynthases.

NRPS-PKS is web-based software for analysing large multi-enzymatic, multi-domain megasynthases that are involved in the biosynthesis of pharmaceutically important natural products such as cyclosporin, rifamycin and erythromycin. NRPS-PKS has been developed based on a comprehensive analysis of the sequence and structural features of several experimentally characterized biosynthetic gene clusters. The results of these analyses have been organized as four integrated searchable databases for elucidating domain organization and substrate specificity of nonribosomal peptide synthetases and three types of polyketide synthases. These databases work as the backend of NRPS-PKS and provide the knowledge base for predicting domain organization and substrate specificity of uncharacterized NRPS/PKS clusters. Benchmarking on a large set of biosynthetic gene clusters has demonstrated that, apart from correct identification of NRPS and PKS domains, NRPS-PKS can also predict specificities of adenylation and acyltransferase domains with reasonably high accuracy. These features of NRPS-PKS make it a valuable resource for identification of natural products biosynthesized by NRPS/PKS gene clusters found in newly sequenced genomes. The training and test sets of gene clusters included in NRPS-PKS correlate information on 307 open reading frames, 2223 functional protein domains, 68 starter/extender precursors and their specific recognition motifs, and also the chemical structure of 101 natural products from four different families. NRPS-PKS is a unique resource which provides a user-friendly interface for correlating chemical structures of natural products with the domains and modules in the corresponding nonribosomal peptide synthetases or polyketide synthases. It also provides guidelines for domain/module swapping as well as site-directed mutagenesis experiments to engineer biosynthesis of novel natural products. NRPS-PKS can be accessed at http://www.nii.res.in/nrps-pks.html.

Databases, Protein↗

PubMed2005

Traveling wave fronts and localized traveling wave convection in binary fluid mixtures.

Nonlinear fronts between spatially extended traveling wave (TW) convection and quiescent fluid and spatially localized traveling waves (LTWs) are investigated in quantitative detail in the bistable regime of binary fluid mixtures heated from below. A finite-difference method is used to solve the full hydrodynamic field equations in a vertical cross section of the layer perpendicular to the convection roll axes. Results are presented for ethanol-water parameters with several strongly negative separation ratios where TW solutions bifurcate subcritically. Fronts and LTWs are compared with each other and similarities and differences are elucidated. Phase propagation out of the quiescent fluid into the convective structure entails a unique selection of the latter while fronts and interfaces where the phase moves into the quiescent state behave differently. Interpretations of various experimental observations are suggested.

Journal Article↗

PubMed1996

Production of intense low-energy positron beams with synchrotron radiation.

A low-energy positron beam is a unique probe of Fermi surfaces, defects, surfaces and interfaces. In high-energy electron and positron storage rings (E > 6 GeV) it is possible to generate intense synchrotron radiation with 1-3 MeV photons by installing a high-field superconducting wiggler. The strength of the wiggler should be ~8-12 T. High-energy photons are emitted from the wiggler and converted to low-energy positrons by using a suitable target-moderator system. For an 8 GeV electron storage ring at a beam current of 100 mA, final yields are estimated to be ~10(10)-10(12) (slow-e(+) s(-1)) with the size of positron source ~10(2)-10(3) cm(2). The possibility of increasing the brightness of the low-energy positron beam is discussed. Advantages of using synchrotron radiation for producing positrons are pointed out. The effect of a superconducting wiggler on the stored electron beam is also discussed.

Journal Article↗

PubMed2004

Diversity of microbial sialic acid metabolism.

Sialic acids are structurally unique nine-carbon keto sugars occupying the interface between the host and commensal or pathogenic microorganisms. An important function of host sialic acid is to regulate innate immunity, and microbes have evolved various strategies for subverting this process by decorating their surfaces with sialylated oligosaccharides that mimic those of the host. These subversive strategies include a de novo synthetic pathway and at least two truncated pathways that depend on scavenging host-derived intermediates. A fourth strategy involves modification of sialidases so that instead of transferring sialic acid to water (hydrolysis), a second active site is created for binding alternative acceptors. Sialic acids also are excellent sources of carbon, nitrogen, energy, and precursors of cell wall biosynthesis. The catabolic strategies for exploiting host sialic acids as nutritional sources are as diverse as the biosynthetic mechanisms, including examples of horizontal gene transfer and multiple transport systems. Finally, as compounds coating the surfaces of virtually every vertebrate cell, sialic acids provide information about the host environment that, at least in Escherichia coli, is interpreted by the global regulator encoded by nanR. In addition to regulating the catabolism of sialic acids through the nan operon, NanR controls at least two other operons of unknown function and appears to participate in the regulation of type 1 fimbrial phase variation. Sialic acid is, therefore, a host molecule to be copied (molecular mimicry), eaten (nutrition), and interpreted (cell signaling) by diverse metabolic machinery in all major groups of mammalian pathogens and commensals.

Amino Acid Sequence↗

PubMed2006

Preferential aggregation of obsessive-compulsive spectrum disorders in schizophrenia patients with obsessive-compulsive disorder.

OBJECTIVE: To validate a complex association between schizophrenia and obsessive-compulsive disorder (OCD). METHOD: We used the Structured Clinical Interview for DSM-IV Axis I disorders to compare the rate of OCD spectrum and additional Axis I disorders in 100 patients who met criteria for both schizophrenia and OCD, non-OCD schizophrenia (n = 100), and OCD (n = 35). RESULTS: There was a robust between-group difference in the number of patients with one or more OCD spectrum disorders (schizo-obsessive n = 30, compared with schizophrenia n = 8; P = 0.001), that is, higher rates of body dysmorphic (8% compared with 0%) and tic (16% compared with 4%) disorders. No difference was revealed in affective, anxiety, and substance use disorders. We found comparable rates of OCD spectrum disorders in the schizo-obsessive and OCD groups (30% and 42.8%, respectively; P = 0.32). CONCLUSION: Preferential aggregation of OCD spectrum disorders in the schizo-obsessive group supports this unique clinical association. Whether a schizo-obsessive interface represents comorbidity or a specific subtype of schizophrenia warrants further investigation.

Adult↗

PubMed2005

Neutrophils, interleukin-17A and lung disease.

It is now established that an excessive and sustained mobilisation of neutrophils is a hallmark of several chronic inflammatory lung disorders, including severe obstructive lung disease. This article reviews evidence that the cytokine interleukin (IL)-17A is a major orchestrator of sustained neutrophilic mobilisation. Current evidence suggests that IL-17A is produced by T-lymphocytes, and that it exerts an orchestrating effect on the accumulation and associated activity of neutrophils in the bronchoalveolar space indirectly, through an induced release of specific cytokines and colony-stimulating factors in resident lung cells. Although the involvement of IL-17A in inflammatory lung disorders is supported by several recent studies, its causative role is still uncertain. However, the unique position of interleukin-17A at the interface between acquired and innate immunity puts this cytokine forward as an important signal for the reinforcement of host defence; it also implies that interleukin-17A may constitute a useful target for pharmacotherapeutic intervention.

Biomarkers↗

PubMed2001

High-turnover periprosthetic bone remodeling and immature bone formation around loose cemented total hip joints.

Aseptic loosening and periprosthetic osteolysis are the major problems awaiting solution in total hip surgery. The clinical investigation focused on the analysis of periprosthetic bone remodeling to clarify one important key event in the cascade of periprosthetic connective tissue weakening and osteolysis around loose artificial hip joints. Twelve acetabular bone samples adjacent to granulomatous synovial-like membrane of loose hip prosthesis were retrieved at revision surgery and processed for Villanueva bone staining for morphological observation and bone histomorphometric analysis. Eight well-fixed bony samples were used as control. Although osteoclastic surface and eroded surface by osteoclasts were evident in the periprosthetic bone from loose hip joints (p = 0.003 and p = 0.027), increased osteoid/low-mineralized bone matrix (p < 0.001) and osteoid width (p < 0.001) also were significant findings in structural analysis. In addition, not only elevated mineral apposition rate (MAR; p = 0.044) but also increased mineralizing surface (p = 0.044) and bone formation rate (BFR; p = 0.002) in loose periprosthetic bones were shown in dynamic data analysis. These results were confirmed by precise morphological observation by confocal laser scanning microscopy. Active coupling of bone formation and resorption and increased osteocytes with abundant bone canalicular projections were found in combined with the presence of immature bone matrices (osteoid and low-mineralized bone areas) in periprosthetic bones from loose hip joints. These results indicated that active osteoclastic bone resorption and/or defective bone formation are coupled with monocyte/macrophage-mediated foreign body-type granuloma in the synovial-like interface membrane of loose hip joints. Thus, this unique high-turnover periprosthetic bone remodeling with bad bone quality probably is caused by the result of cellular host response combined with inappropriate cyclic mechanical loading. The fragile periprosthetic bone may contribute to hip prosthesis loosening.

Aged↗

PubMedDate not supplied

Histologic evaluation of a 9-year-old hydroxyapatite-coated cylindric implant placed in conjunction with a subantral augmentation procedure: a case report.

The histologic examination of dental implants retrieved from humans provides a unique opportunity to evaluate the bone-implant interface. This case report presents a clinical, radiographic, and histologic evaluation of a cylindrical hydroxyapatite- (HA) coated implant retrieved from the posterior maxillary area of a patient after 9 years after placement. The implant had been placed in conjunction with a subantral augmentation procedure with HA as the graft material. Clinical examination revealed an immobile implant with no sign of pathosis. Radiographic examination indicated close proximity of the bone to the implant surface without evidence of radiolucency. Histologically, because of tissue destruction during implant retrieval, only the apical portion of the implant was available for examination under light microscopy, and it appeared to be integrated with the surrounding bone; 45.9% of the surface of the implant had close bone apposition at the interface. There was no evidence of dissolution of the HA coating and the bone appeared to be in immediate contact with the coating. Residual graft particles were present and in close proximity with the implant surface. These observations suggest that the subantral augmentation procedure performed simultaneously with the placement of an HA-coated implant with HA as the graft material apparently resulted in osseointegration between the implant and the surrounding bone. The implant was maintained without complication for 9 years.

Alveolar Ridge Augmentation↗

PubMed1977

Ultrasonic diagnosis of renal and retroperitoneal lesions.

The unique ability of ultrasound to detect soft tissue interfaces makes it a prime tool for at least one major diagnostic approach to soft tissue lesions. Systematic ultrasonic examination of suspected masses in the abdomen should be performed early in the course of investigation. It will help direct additional studies and often result in cost savings by making the diagnostic process more efficient. The method is painless, to the best of our knowledge harmless and can be repeated at will for early study or late follow-up. The ultrasonic look into the body has provided us with a major tool for obtaining far more information on internal structures than was possible even a few years ago. Ultrasonic scans, radioisotope examinations and computerized x-ray tomography are leading us into an era of much increased anatomic knowledge about lesions which heretofore were obscure and difficult to evaluate.

Abdominal Neoplasms↗

PubMed1981

Digital approaches to myoelectric state control of prostheses.

The design of a new three-state myoelectric control system is presented. This controller determines its operating state from the initial rate of increase of the myoelectric signal, and the concept is realized in great measure through digital logic techniques. Proportional control of both active states (same dynamic range) is a unique feature of the controller. A microcomputer was interfaced in a simple way with myoelectric potentials to simulate the three-state controller described and to simulate various other state-determined control methods (some multifunctional). This was found to be a valuable method of evaluating control schemes without building the actual devices.

Adult↗