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 487 records · Page 27Linked to original sources

PubMed2003

Identification of a heteromeric interaction that influences the rectification, gating, and pH sensitivity of Kir4.1/Kir5.1 potassium channels.

Heteromultimerization between different potassium channel subunits can generate channels with novel functional properties and thus contributes to the rich functional diversity of this gene family. The inwardly rectifying potassium channel subunit Kir5.1 exhibits highly selective heteromultimerization with Kir4.1 to generate heteromeric Kir4.1/Kir5.1 channels with unique rectification and kinetic properties. These novel channels are also inhibited by intracellular pH within the physiological range and are thought to play a key role in linking K+ and H+ homeostasis by the kidney. However, the mechanisms that control heteromeric K+ channel assembly and the structural elements that generate their unique functional properties are poorly understood. In this study we identify residues at an intersubunit interface between the cytoplasmic domains of Kir5.1 and Kir4.1 that influence the novel rectification and gating properties of heteromeric Kir4.1/Kir5.1 channels and that also contribute to their pH sensitivity. Furthermore, this interaction presents a structural mechanism for the functional coupling of these properties and explains how specific heteromeric interactions can contribute to the novel functional properties observed in heteromeric Kir channels. The highly conserved nature of this structural association between Kir subunits also has implications for understanding the general mechanisms of Kir channel gating and their regulation by intracellular pH.

Amino Acid Sequence↗

PubMed2003

Targeting NS5B RNA-dependent RNA polymerase for anti-HCV chemotherapy.

The global prevalence of persistent hepatitis C virus (HCV) infection and the lack of a highly effective and well-tolerated antiviral therapy have spurred intensive efforts to discover and develop novel anti-HCV therapy in the pharmaceutical industry. HCV NS5B RNA-dependent RNA polymerase (RdRp), the centerpiece for viral replication, constitutes a valid target for drug discovery. Compared to the host RNA and DNA polymerases, NS5B RdRp has distinct subcellular localization at the interface of the endoplasmic reticulum (ER) membrane and cytoplasm, a novel catalytic mechanism and many unique structural features, all of which make it an attractive target for developing effective anti-HCV therapeutics. High genetic variation among the major HCV genotypes commands that any efficacious NS5B inhibitors have to be broadly active against NS5Bs from various genotypes. Rapid viral replication and its inherent genetic diversity will certainly culminate drug resistance to any NS5B inhibitors. Therefore, iterative drug design and combination therapies of drugs that intervene with different steps in the HCV replicative cycle are needed to combat the viral infection. Many classes of nucleoside and non-nucleoside inhibitors of NS5B RdRp have been identified and appeared in literatures and patent applications. These progresses hold a considerable promise to the development of novel, specific and highly effective therapeutics to achieve sustained response and ultimately the eradication of HCV infection.

Amino Acid Sequence↗

PubMed2001

Targets of anti-influenza chemotherapy other than neuraminidase and proton pump.

Antiviral chemotherapy for influenza started with treatment with amantadine and then progressed with finding the clinical efficacy of neuraminidase (NA) inhibitors. Beside amantadine and NA inhibitors, there are several compounds that attack novel targets of influenza virus (FluV) replication. Binding and penetration of FluV to cell membrane are important stages in the process of virus replication, and several compounds that inhibit these functions have been reported, although most of them have yet to be examined for clinical use. A polyoxometalate (PM523) was shown to be potent inhibitor of FluV A, respiratory syncytial virus and measles virus, and was shown to inhibit membrane fusion between FluV envelope and the cellular membrane. Strains of virus with acquired resistance to PM523 had mutations in the amino acids substrates in HA1 head, and amino acid changes occurred in the interface peptide of the trimers of HA. Cap formation of FluV-encoded mRNA is unique; it utilizes 5'-mGpppXm of host mRNA. Several substances which inhibit the cap formation of FluV (they are inhibitors of PB2 enzyme activity of FluV) are introduced and reviewed in this article. A metabolic product of ribavirn, 1,2,4 triazole carboxamide (T-CONH2) is inhibitory for FluV A growth in vitro. Peroral administration of TCONH2 also showed therapeutic effect in an experimental mouse infection model of FluV A as well as ribavirin. TCONH2 seems to be less toxic than ribavirin for mice, and may be useful as alternative chemotherapy of ribavirin. Other anti-FluV substances that have been reported to be effective for FluV infection in the mouse are discussed with respect to the possibility of their clinical potential.

Animals↗

PubMed1992

A graphical user interface for quantitative imaging and analysis of electrophoretic gels and autoradiograms.

DNA/GUI (DNA Graphical User Interface) is an interactive software system for rapid and efficient analysis of images of the types used in genome mapping, such as autoradiograms and electrophoretic gels. Images are digitized using a commercially available charge-coupled-device (CCD) camera system and analyzed on a graphics workstation using a menu-driven user interface. DNA/GUI features automatic lane and band detection, simultaneous display of multiple images and a unique spatial-normalization algorithm. Images and their associated data are archived and easily available for later recall. Preliminary results indicate that DNA/GUI is a useful tool in the analysis and comparison of images used in a variety of applications such as genetic-linkage analysis and DNA restriction mapping. The interactive display software is based on the X Window System and is therefore readily portable to a variety of graphics workstations.

Autoradiography↗

PubMed1991

Air interface and elastic recoil affect vascular resistance in three zones of rabbit lungs.

We examined the effect of the air interface on pulmonary vascular resistance (PVR) in zones 1, 2, and 3 by comparing pressure-flow data of air- and liquid-filled isolated rabbit lungs. Lungs were perfused with Tyrode's solution osmotically balanced with 1% albumin and 4% dextran and containing the vasodilator papaverine (0.05 mg/ml). Lung volume was varied by negative pleural pressure form 0 to -25 cmH2O. Pulmonary artery (Ppa) and venous (Ppv) pressures were fixed at various levels relative to the lung base. Alveolar pressure (PA) was always zero, and perfusate flow was measured continuously. In zone 1 Ppa was -2.5 cmH2O and Ppv was -15 cmH2O. In zone 2 Ppa was 10 cmH2O and Ppv was -5 cmH2O. In zone 3 Ppa was 15 cmH2O and Ppv was 8 cmH2O. We found that in zone 1 the interface was essential for perfusion, but in zones 2 and 3 it had much lesser effects. In general, PVR depended almost uniquely (i.e., with small hysteresis) on transpulmonary pressure, whereas a large hysteresis existed between PVR and lung volume. PVR was high in collapsed and especially in atelectatic lungs, fell sharply with moderate inflation, and within the ranges of vascular pressure studied did not rise again toward total lung capacity. These results suggest that in zone 1 the interface maintains the patency of some alveolar vessels, probably in corners. The majority of alveolar septal vessels appears to be exposed directly to PA in zones 2 and 3, because at equal transpulmonary pressure the PVR is similar in the presence or absence of an interface.

Air↗

PubMed2001

Real-time interaction between a neuromorphic electronic circuit and the spinal cord.

We present a novel demonstration of real-time dynamic interaction between an oscillatory spinal cord (isolated lamprey nervous system) and electronic hardware that mimics the spinal motor pattern generating circuitry. The spinal cord and the neuromorphic circuit were interfaced in unidirectional and bidirectional modes. Bidirectional coupling resulted in stable, persistent oscillations. This experimental platform offers a unique paradigm to examine the intrinsic dynamics of neural circuitry. The neuromorphic analog very large scale integration (aVLSI) design and real-time capabilities of this approach may provide a particularly powerful means of restoring complex neuromotor function using neuroprostheses.

Animals↗

PubMed2004

Micromechanical analysis of dentin/adhesive interface by the finite element method.

The interfacial microstructure and spatial distribution of the modulus of elasticity have a profound effect on load transfer at the dentin/adhesive (d/a) interface. The microstructure is influenced by the varying degree of demineralization of intertubular and peritubular dentin during etching as well as the depth of adhesive penetration into the hybrid layer. These factors lead not only to a unique microstructure in the vicinity of the dentinal tubules, but also to a mechanically graded hybrid layer. This article investigates the micromechanical stress distribution at a d/a interface with the use of finite element analysis (FEA). Such analysis is now feasible given the newly measured moduli of elasticity at micro- and nanoscales. The results indicate that the morphological and micromechanical properties of the d/a interface affects the stress field such that the fracture/failure is likely to initiate in the stress-concentration zone of peritubular dentin next to the hybrid/exposed-collagen layer. The results suggest that devising a full-depth high modulus hybrid layer may considerably reduce the stress concentration zone and the magnitude of stress concentration in the peritubular dentin next to the hybrid/exposed-collagen layer.

Adhesives↗

PubMed2005

BioCloneDB: A Database Application to Manage DNA Sequence and Gene Expression Data.

UNLABELLED: BioCloneDB is a user-friendly database with a web interface to assist molecular genetics laboratories in managing a local repository of sequence information linked to DNA clones. This tool is designed to assist in high-throughput sequence and gene expression projects, providing a link between both types of information. The unique feature of the application is the automation of batch sequence annotation following BLAST((R)) searches, which is supported by easy-to-use web interfaces. Furthermore, any set of sequences can be annotated against any sequence database. This replaces the need to perform and analyse individual web BLAST((R)) searches or the need to learn how to produce batch searches and perform analysis in a UNIX((R)) operating system. BioCloneDB is open-source software that can be installed on Linux or UNIX((R)) operating systems. To test the application, we used 1400 expressed sequence tags obtained from the filamentous fungus Neurospora crassa. The results were analysed and compared with published results and they show a significant change due to the accumulation of the data in the nr database (ftp://ftp.ncbi.nih.gov/blast/db/). AVAILABILITY: BioCloneDB is available for academic use along with documentation, screenshots, database scheme and readme files at http://bioclonedb.agri.huji.ac.il/ CONTACT: Oded Yarden (Oded.Yarden@huji.ac.il).

Journal Article↗

PubMed1996

The unique endometrial expression and genomic organization of the porcine IGFBP-2 gene.

The insulin-like growth factor-binding proteins (IGFBPs-1-6) modulate the mitogenic and differentiative actions of the IGFs and may have IGF-independent functions. This study examined the gene expression and pregnancy-regulation of the IGF/IGFBP system in porcine uterine endometrium and myometrium during the periimplantation period and later stages of pregnancy. Endometrial IGFBP-2 mRNA abundance exhibited stage of pregnancy-dependent induction; whereas little or no IGFBP-2 mRNA was found in myometrium. IGFBP-2 protein was immunolocalized to the endometrial glandular and luminal epithelia (staining on day 60 > day 12) with minimal or no immunostaining of uterine stroma observed. IGFBP-3 and IGFBP-4 transcript levels became elevated in endometrium after implantation; whereas, IGFBP-5 and IGFBP-6 mRNAs were in greater abundance in periimplantation than post-implantation endometrium. IGFBP-1 transcripts, in contrast, could not be identified in porcine endometrium or myometrium of pregnancy. As a pre-requisite to understanding the pregnancy-induction and endometrial-specificity of the uterine-expressed IGFBP-2 gene, cosmids encompassing the pig IGFBP-2 chromosomal locus were isolated and characterized. This gene is comprised of four exons that span > 29 kb and encode a 316 amino acid precursor protein. All four exons were found to be G/C rich with exon 1 and immediate 5' flank exhibiting hallmarks of a CpG island. This latter region was devoid of TATA and CAAT motifs. Results identify the preferential endometrial expression of different IGFBP genes at either the periimplantation or post-implantation periods, perhaps reflecting distinct actions of these proteins at the embryo-maternal and feto-maternal interfaces, respectively. Interactions of steroid receptors, endometrial transcription factors and their corresponding cis elements may confer the unique uterine expression of the IGFBP-2 gene.

Amino Acid Sequence↗

PubMed2005

Dynamic expression of matrix metalloproteinases (MMP-2, -9 and -14) and the tissue inhibitors of MMPs (TIMP-1, -2 and -3) at the implantation site during tubal pregnancy.

Matrix metalloproteinases (MMPs) are responsible for extracellular matrix (ECM) degradation, and their functions are regulated by tissue inhibitors of MMPs (TIMPs). The evidence for the roles of MMPs and TIMPs in implantation and placentation has remained insufficient in humans, especially during the early stages. Tubal pregnancy has some similarities to normal intrauterine pregnancy and therefore may provide a unique model for implantation studies. In the present study, the expression of MMP-2, -9 and -14, and TIMP-1, -2 and -3 at the feto-maternal interface during tubal pregnancy was examined by immunohistochemistry and in situ hybridization. We found that MMP-9 and TIMP-1, -2 and -3 are produced by all types of extravillous cytotrophoblast (EVCT) cells, while MMP-2 and -14 mainly exist in distal column cytotrophoblast (CCT) cells and invasive EVCT cells. Meanwhile, the intensity of MMP-14 and TIMP-1 and -2 increased along the invasive pathway toward maternal interstitium. In addition, MMP-2, -9 and -14 and TIMP-1, -2 and -3 were all detected in the villous CT (VCT) cells. Furthermore, both the mRNA level and immunoreactivity of MMP-9, TIMP-1 and -3 increased, while those of TIMP-2 decreased concurrent with the progression of pregnancy during weeks 3-9. The unique expression pattern of various MMPs and TIMPs at the feto-maternal interface suggests that they may have roles in regulating the controlled invasion of trophoblasts during implantation and placentation. Meanwhile, the study provides a better understanding of the mechanisms involved in cellular events during human pregnancy, especially at the initiation stage of implantation.

Embryo Implantation↗

PubMed2004

Structural and functional analysis of mutations at the human hypoxanthine phosphoribosyl transferase (HPRT1) locus.

Hypoxanthine phosphoribosyl transferase (HPRT, also known as HGPRT) is an often-used genetic marker in eukaryotic cells. The gene is conserved from bacteria to human, with retained catalytic activity, although substrate specificity may have changed, and the enzyme is essential in malaria-causing protozoans. Inherited mutations in the human HPRT1 gene result in three different phenotypes: Lesch-Nyhan syndrome (LNS or LND), LND variants, and HPRT-related hyperuricemia (HRH). In cultured cells, loss of HPRT activity gives rise to 6-thioguanine (6-TG) resistance. In general, cells from LND patients are also 6-TG resistant, whereas cells from HRH patients are not, with some interesting exceptions. Using modeling methods, we have studied the correlation between the mutable and nonmutated amino acid residues on one hand, and sequence conservation and predicted phenotypic effects on the other hand. Our results demonstrate that most of the mutations are explainable by the predicted effect on protein structure and function. They are also consistent with sequence conservation. Moreover, the mutational profiles of TG-resistant cells and LND overlap to a great extent, while most of the mutations in HRH are unique to that condition. We have also noticed a strong correlation between mutations in the tetramer interfaces and observed phenotypes, suggesting a functional role for a tetramer transition during catalysis.

Amino Acid Sequence↗

PubMed1992

A case of pigmentary type of orthochromatic leukodystrophy with early onset and globoid cells.

We report herein a sporadic case of the pigmentary type of orthochromatic leukodystrophy with early onset and very rapid clinical course. The patient's development was normal until 2 years old, when he experienced visual disturbance. Rapid deterioration resulted in death 1.5 years after the onset. Metachromatic leukodystrophy, globoid cell leukodystrophy and adrenoleukodystrophy were excluded by biochemical assays. Autopsy findings were compatible with the diagnosis of the pigmentary type of orthochromatic leukodystrophy. However, there were unique findings of severe neuronal loss and the collection of globoid-like cells in the interface of the gray matter and the white matter. Immunohistochemical staining of myelin basic protein, proteolipid protein and galactocerebroside demonstrated that these myelin constituents were equally preserved in the posterior column, while absent in the lateral and anterior columns of the spinal cord.

Autopsy↗

PubMed2002

Magnetization transfer short inversion time inversion recovery enhanced 1H MRI of the human lung.

The unique characteristics of the human lung arising from low proton density and multiple air-tissue interfaces of the alveoli cause difficulty in 1H lung magnetic resonance imaging. In addition, the dominating signal from sources such as the thoracic muscle and subcutaneous fat hampers the visualization of the lung parenchyma. In this contribution, an efficient tissue suppression technique is presented which allows one to significantly enhance lung parenchyma visibility. A short inversion time inversion recovery (STIR) experiment combined with a magnetization transfer (MT) experiment was used for magnetization preparation in order to suppress the signal from muscle. A half-Fourier single-shot turbo spin-echo sequence was used as acquisition module. This approach was used to perform lung anatomical imaging in eight healthy human subjects and five patients with cystic fibrosis. The results obtained demonstrate that with MT-STIR approach high quality human lung images can be obtained and that this approach has the potential for the evaluation of lung pathologies.

Adult↗

PubMed2003

Atypical morphology of dark septate fungal root endophytes of Bouteloua in arid southwestern USA rangelands.

Native grasses of semi-arid rangelands of the southwestern USA are more extensively colonized by dark septate endophytes (DSE) than by traditional mycorrhizal fungi. Roots of dominant grasses ( Bouteloua sp.) native to arid southwestern USA rangelands were prepared and stained using stains specific for fungi (trypan blue) and for lipids (sudan IV). This revealed extensive internal colonization of physiologically active roots by atypical fungal structures that appear to function as protoplasts, without a distinguishable wall or with very thin hyaline walls that escape detection by methods staining specifically for fungal chitin. These structures were presumed to be active fungal stages that progressed to form stained or melanized septate hyphae and microsclerotia characteristic of DSE fungi within dormant roots. The most conspicuous characteristic of these fungi were the unique associations that formed within sieve elements and the accumulation of massive quantities of lipids. This interface suggests a biologically significant location for carbon transfer between the plant and fungus. The continuous intimate association with all sieve elements, cortical and epidermal cells as well as external extension on the root surface and into the soil indicates that they are systemic and considerably more prevalent than previously thought. A fungal network associated with a mucilaginous complex observed on the root surface and its potential role in root function in dry soil is discussed. It is suggested that those fungi that non-pathogenically and totally colonize plant cells be classed as systemic endophytic fungi (SEF). This would refine the broad designation of DSE fungi. The potential mutualistic benefit of SEF for native plants in arid ecosystems based on the extent of lipid accumulation and its apparent distribution is discussed.

Desert Climate↗

PubMed2006

A multiple PCR-primer approach to access the microeukaryotic diversity in environmental samples.

The Cariaco Basin off the Venezuelan coast in the Caribbean Sea is the world's largest truly marine body of anoxic water. The first rRNA survey of microbial eukaryotes in this environment revealed a number of novel lineages, but sampled only a fraction of the entire diversity. The goal of this study was to significantly improve recovery of protistan rRNA from the Basin. This was achieved by a systematic application of multiple PCR primer sets and substantially larger sequencing efforts. We focused on the most diverse habitat in the basin, anoxic waters approximately 100m below the oxic-anoxic interface, and detected novel lineages that escaped the single PCR primer approach. All clones obtained proved unique. A 99% sequence similarity cut-off value combined these clones into operational taxonomic units (OTUs), over 75% of which proved novel. Some of these OTUs form deep branches within established protistan groups. Others signify discovery of novel protistan lineages that appear unrelated to any known microeukaryote. Surprisingly, even this large-scale multi-primer rRNA approach still missed a substantial part of the samples' rRNA diversity. The overlap between the species lists obtained with different primers is low, with only 4% of OTUs shared by all three libraries, and the number of species detected only once is large (55%). This strongly indicates that, at least in anoxic environments, protistan diversity may be much larger than is commonly thought. A single sample appears to contain thousands of largely novel protistan species. Multiple PCR primer combinations may be needed to capture these species.

Animals↗

PubMed2005

The molecular origins of specificity in the assembly of a multienzyme complex.

The pyruvate dehydrogenase (PDH) multienzyme complex is central to oxidative metabolism. We present the first crystal structure of a complex between pyruvate decarboxylase (E1) and the peripheral subunit binding domain (PSBD) of the dihydrolipoyl acetyltransferase (E2). The interface is dominated by a "charge zipper" of networked salt bridges. Remarkably, the PSBD uses essentially the same zipper to alternately recognize the dihydrolipoyl dehydrogenase (E3) component of the PDH assembly. The PSBD achieves this dual recognition largely through the addition of a network of interfacial water molecules unique to the E1-PSBD complex. These structural comparisons illuminate our observations that the formation of this water-rich E1-E2 interface is largely enthalpy driven, whereas that of the E3-PSBD complex (from which water is excluded) is entropy driven. Interfacial water molecules thus diversify surface complementarity and contribute to avidity, enthalpically. Additionally, the E1-PSBD structure provides insight into the organization and active site coupling within the approximately 9 MDa PDH complex.

Binding Sites↗

PubMed2004

The immunological paradox of pregnancy: a reappraisal.

The survival of the allogeneic conceptus has long been an immunological paradox. Medawar was the first to propose an evasive mechanism based on the concept of self/non-self recognition described in classical transplantation immunology. Since then, several newer models of self/non-self recognition have been proposed, such as the PAMP/PRR system, the Missing Self and the Danger Hypothesis. The present paper considers the fetal-maternal relationship in the context of all these models. The conclusion reached is that none of them is really appropriate because the interface between trophoblast cells of the fetal placenta and the leukocytes of the maternal decidua is unique. Pregnancy is not simply a case of acceptance or rejection like a transplant. The immunological mechanism must provide a balanced environment whereby the conceptus is nurtured by the mother and yet prevented from excessive invasion. Future identification of trophoblast ligands and their respective receptors on uterine Natural Killer cells and other leukocytes is likely to offer the best insight as to how this symbiotic state is achieved.

Female↗

PubMed2001

A miniaturized liquid core waveguide-capillary electrophoresis system with flow injection sample introduction and fluorometric detection using light-emitting diodes.

A novel miniaturized capillary electrophoresis (CE) system is described where a Teflon AF-coated silica capillary serves both as the separation channel and as a transversely illuminated liquid core waveguide. This device uniquely uses flow injection (FI)-based split-flow sample introduction through a falling-drop interface. An H-channel structure fixed on a microscope glass slide utilizes a horizontal separation capillary with tubular sidearms on each end that serve as inlet and outlet flow-through electrode reservoirs. The inlet reservoir also functions as a falling-drop interface for coupling to the FI system. A blue LED is used as excitation source. A large-core optical fiber takes the emitted fluorescence to an inexpensive PMT with two layers of green plastic used for optical filtering. No focusing arrangement is needed. Continuous FI introduction of a series of 30-microL samples containing a mixture of of fluorescein isothiocyanate (FITC)-labeled amino acids allowed a throughput rate up to 144 samples/ h, with approximately 2% carryover and good precision (3.2% RSD). Baseline separation was achieved for FITC-labeled arginine, phenylalanine, glycine, and FITC in sodium tetraborate buffer (pH 9.5) with plate heights of 5.4-5.5 microm and plate numbers of 2.34 x 10(4)-2.37 x 10(4) under electrical field strengths of 214 V/cm for injection and 500 V/cm for separation (14-cm capillary, 48-microm i.d.). Detection limits (S/N = 3) were 1.3 microM for arginine and 1.9 microM for phenylalanine and glycine.

Amino Acids↗