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At least 757 records · Page 42Linked to original sources

PubMed1991

Remembered odors and mental mixtures: tapping reservoirs of olfactory knowledge.

Five experiments explored how (a) perceived and remembered odor intensities relate to concentration; (b) odor intensities integrate in perceptual, memorial, and mentally constructed mixtures; and (c) components vary in intensity in physical versus mental mixtures. Ss estimated the magnitude of unmixed stimuli presented physically (perceptual estimation) or represented symbolically (memorial estimation). Ss also judged mixtures and their components in combinations of perceptual and memorial presentation. Power functions with similar exponents described the relations between both perceived and remembered intensity and concentration. Perceptual, memorial, and mental mixtures all followed much the same interactive rule of integration. Correspondingly, the intensities of components varied similarly in mentally constructed and physical mixtures. The results imply intensive invariance across odor perception and odor memory.

Adult↗

PubMed1996

The yeast nucleoporin Nup188p interacts genetically and physically with the core structures of the nuclear pore complex.

We have isolated a major protein constituent from a highly enriched fraction of yeast nuclear pore complexes (NPCs). The gene encoding this protein, Nup188p, was cloned, sequenced, and found to be nonessential upon deletion. Nup188p cofractionates with yeast NPCs and gives an immunofluorescent staining pattern typical of nucleoporins. Using immunoelectron microscopy, Nup188p was shown to localize to both the cytoplasmic and nucleoplasmic faces of the NPC core. There, Nup188p interacts with an integral protein of the pore membrane domain, Pom152p, and another abundant nucleoporin, Nic96p. The effects of various mutations in the NUP188 gene on the structure of the nuclear envelope and the function of the NPC were examined. While null mutants of NUP188 appear normal, other mutants allelic to NUP188 exhibit a dominant effect leading to the formation of NPC-associated nuclear envelope herniations and growth inhibition at 37 degrees C. In addition, depletion of the interacting protein Pom152p in cells lacking Nup188p resulted in severe deformations of the nuclear envelope. We suggest that Nup188p is one of a group of proteins that form the octagonal core structure of the NPC and thus functions in the structural organization of the NPC and nuclear envelope.

Amino Acid Sequence↗

PubMed1988

Effects of glycerol concentration, equilibration time and temperature of glycerol addition on post-thaw viability of boar spermatozoa frozen in straws.

Experiments were conducted to study the effect of glycerol concentration, equilibration time and temperature of glycerol addition on post-thaw viability of boar spermatozoa after cryopreservation in straws. Semen (split ejaculate) in maxi-straws (6 mm o.d.) was frozen using a programmable freezing chamber. Three methods for in vitro sperm evaluation were used: motility (MOT), acrosome integrity (NAR) and flow cytometric analysis of sperm treated with carboxyfluorescein diacetate and propidium iodide to assess sperm plasma membrane integrity (PMI). No interactions were found among the three variables evaluated. Length of prefreeze exposure to glycerol, ranging from .5 min to 75 min, had no effect on post-thaw sperm viability. Exposure of sperm to a glycerol-containing extender medium at 5 degrees C gave improved post-thaw viability over that exposed at 0 degree C (P less than .05). Glycerol at a concentration of 3 or 4% resulted in maximum post-thaw MOT. Acrosome integrity values were greatest for 2 and 3% glycerol, whereas PMI was greatest when glycerol concentration was 4 to 6%. The primary cryoprotective effect of glycerol on boar semen may be extracellular. It is concluded that 3 or 4% glycerol gives maximum viability of frozen-thawed spermatozoa when the present methods are employed.

Acrosome↗

PubMed1998

The yeast centrin, cdc31p, and the interacting protein kinase, Kic1p, are required for cell integrity.

Cdc31p is the yeast homologue of centrin, a highly conserved calcium-binding protein of the calmodulin superfamily. Previously centrins have been implicated only in microtubule-based processes. To elucidate the functions of yeast centrin, we carried out a two-hybrid screen for Cdc31p-interacting proteins and identified a novel essential protein kinase of 1,080 residues, Kic1p (kinase that interacts with Cdc31p). Kic1p is closely related to S. cerevisiae Ste20p and the p-21- activated kinases (PAKs) found in a wide variety of eukaryotic organisms. Cdc31p physically interacts with Kic1p by two criteria; Cdc31p coprecipitated with GST-Kic1p and it bound to GST-Kic1p in gel overlay assays. Furthermore, GST-Kic1p exhibited in vitro kinase activity that was CDC31-dependent. Although kic1 mutants were not defective for spindle pole body duplication, they exhibited a variety of mutant phenotypes demonstrating that Kic1p is required for cell integrity. We also found that cdc31 mutants, previously identified as defective for spindle pole body duplication, exhibited lysis and morphological defects. The cdc31 kic1 double mutants exhibited a drastic reduction in the range of permissive temperature, resulting in a severe lysis defect. We conclude that Kic1p function is dependent upon Cdc31p both in vivo and in vitro. We postulate that Cdc31p is required both for SPB duplication and for cell integrity/morphogenesis, and that the integrity/morphogenesis function is mediated through the Kic1p protein kinase.

Actins↗

PubMed1998

The NH2 terminus of titin spans the Z-disc: its interaction with a novel 19-kD ligand (T-cap) is required for sarcomeric integrity.

Titin is a giant elastic protein in vertebrate striated muscles with an unprecedented molecular mass of 3-4 megadaltons. Single molecules of titin extend from the Z-line to the M-line. Here, we define the molecular layout of titin within the Z-line; the most NH2-terminal 30 kD of titin is located at the periphery of the Z-line at the border of the adjacent sarcomere, whereas the subsequent 60 kD of titin spans the entire width of the Z-line. In vitro binding studies reveal that mammalian titins have at least four potential binding sites for alpha-actinin within their Z-line spanning region. Titin filaments may specify Z-line width and internal structure by varying the length of their NH2-terminal overlap and number of alpha-actinin binding sites that serve to cross-link the titin and thin filaments. Furthermore, we demonstrate that the NH2-terminal titin Ig repeats Z1 and Z2 in the periphery of the Z-line bind to a novel 19-kD protein, referred to as titin-cap. Using dominant-negative approaches in cardiac myocytes, both the titin Z1-Z2 domains and titin-cap are shown to be required for the structural integrity of sarcomeres, suggesting that their interaction is critical in titin filament-regulated sarcomeric assembly.

Actinin↗

PubMed1993

Hippocampal extracellular space micro-EEG--high frequency oscillations.

The hippocampal extracellular space electro-magnetic field interactions and related integrative mechanisms are important factors in the make-up of the micro-EEG. Combinations of ion currents give rise to complex patterns of neuronal electrical activity in the brain cell microenvironment, the extracellular space. The flow of ions through populations of ion channels in the neuronal plasma membrane and give rise to trans membrane ion currents. It is the sum of various currents flowing at any point in time that determines the neurons membrane potential. The multiple ion channels with their diverse and interacting regulatory mechanisms allow the neuron to modulate its electrical properties in complex ways of high frequency oscillations and electrical fields. Some of the hippocampal neurons have ionic conductances organized to endow them with auto rhythmicity. In many neurons the kinetics of these ionic voltage dependent conductances are such that the cells may respond preferentially to inputs at a certain frequency or frequencies acting as a resonators.

Amygdala↗

PubMed1996

Coordinate activation of c-Src by SH3- and SH2-binding sites on a novel p130Cas-related protein, Sin.

To understand how protein-protein interactions mediated by the Src-SH3 domain affect c-Src signaling, we screened for proteins that interact with the Src-SH3. We found a novel protein, Sin (Src interacting or signal integrating protein), that binds to Src-SH3 with high affinity, contains numerous tyrosine residues in configurations suggestive of SH2-binding sites, and is related to the v-Src substrate p130Cas. In cotransfection assays, a small fragment of Sin retaining the Src-SH3-binding site and one tyrosine-containing motif induced c-Src activation as measured by a transcriptional reporter. Phosphorylation of the peptide on tyrosine by c-Src, as a consequence of Src-SH3 binding, was necessary for its stable interaction with c-Src in vivo and for transcriptional activation. Phosphorylation of multiple tyrosine-containing motifs found on Sin correlated with c-Crk and cellular phosphoprotein binding to Sin as well as increased c-Src activity. These data suggest that (1) SH2 and SH3 ligand sites on Sin cooperatively activate the signaling potential of c-Src, (2) Sin acts as both an activator and a substrate for c-Src, and (3) phosphorylated Sin may serve as a signaling effector molecule for Src by binding to multiple cellular proteins.

Amino Acid Sequence↗

PubMed1997

In vivo cleavage of Escherichia coli BIME-2 repeats by DNA gyrase: genetic characterization of the target and identification of the cut site.

The Escherichia coli chromosome contains about 300 bacterial interspersed mosaic elements (BIMEs). These elements, located at the 3' end of genes, are composed of three types of alternating repetitive extragenic palindromes (REPs). Based on the type of REP they contain and on their ability to interact with the integration host factor (IHF), BIMEs are subdivided into two families: BIME-1 elements contain an IHF binding site flanked by converging Y and Z1 REPs, whereas BIME-2 elements contain a variable number of alternating Y and Z2 REPs without an IHF site. Although some BIMEs have been implicated in the protection of mRNA against 3' exonucleolytic degradation, the main role of elements belonging to both families remains to be elucidated. In this paper, we used oxolinic acid, a drug that reveals potential sites of DNA gyrase action, to demonstrate that DNA gyrase interacts in vivo with BIME-2 elements. The frequency of cleavage varied from one element to another, and the cleavage pattern observed in elements containing several REPs indicated that DNA gyrase cut DNA every two REPs. A single cleavage site has been identified in the Y REP in six out of seven instances, and the nucleotide sequence of a 44 bp fragment containing the scission point displayed conserved residues at six positions. The lack of one of the conserved residues accounted for the absence of cleavage in most of the Z2 REPs. Our results also showed that cleaved REPs were always associated with another REP, suggesting that a pair of diverging REPs constitutes the target of DNA gyrase. DNA gyrase cleavage at repetitive BIME-2 elements may have consequences for DNA topology and genomic rearrangements.

Base Sequence↗

PubMed1998

Endothelial integrity, soluble adhesion molecules and platelet markers in type 1 diabetes mellitus.

Recent developments in cell biology have identified new areas of direct relevance to the pathogenesis of Type 1 (insulin-dependent) diabetes mellitus and its complications. Endothelial damage is well recognized in diabetes--endothelial cell markers von Willebrand factor, soluble E-selectin, and soluble thrombomodulin are providing further evidence of the relationship between activation and damage to the vasculature and clinical disease in this condition. Cell surface bound adhesion molecules may also have a role in the development of atherosclerosis in patients with diabetes but the importance of the soluble forms of these molecules, such as intercellular adhesion molecule-1, is unclear. Evidence of platelet dysfunction has long been acknowledged in diabetes and new data are discussed. It is likely that a greater appreciation of the intimate interactions between endothelial integrity, adhesion molecules and platelets in Type 1 diabetes mellitus will provide a greater understanding of the risk of cardiovascular disease and stroke in patients with this disorder.

Arteriosclerosis↗

PubMed1999

Mechanisms for spatial integration in visual detection: a model based on lateral interactions.

Recent studies of visual detection show a configuration dependent weak improvement of thresholds with the number of targets, which corresponds to a fourth-root power law. We find this result to be inconsistent with probability summation models, and account for it by a model of 'physiological' integration that is based on excitatory lateral interactions in the visual cortex. The model explains several phenomena which are confirmed by the experimental data, such as the absence of spatial and temporal uncertainty effects, temporal summation curves, and facilitation by a pedestal in 2AFC tasks. The summation exponents are dependent on the strength of the lateral interactions, and on the distance and orientation relationship between the elements.

Computer Simulation↗

PubMed2003

Combinatorial function of the homeodomain proteins Nkx2.1 and Gsh2 in ventral telencephalic patterning.

Regional patterning of the mammalian telencephalon requires the function of three homeodomain-containing transcription factors, Pax6, Gsh2 and Nkx2.1. These factors are required for the development of the dorsal, lateral and medial domains of the telencephalon, respectively. Previous work has indicated that two of the genes encoding these factors, Pax6 and Gsh2, cross-repress one another in the formation of the border between dorsal and lateral region of the telencephalon. Here, we examine whether similar interactions are responsible for the establishment of other boundaries of telencephalic gene expression. Surprisingly, despite the fact that, at specific times in development, both Pax6 and Gsh2 maintain a complementary pattern of expression with Nkx2.1, in neither case are these boundaries maintained through a similar cross-repressive mechanism. Rather, as revealed by analysis of double-mutant mice, Nkx2.1 and Gsh2 act cooperatively in many aspects to pattern the ventral telencephalon. By contrast, as indicated by both loss- and gain-of-function analysis, Gsh2 expression in the medial ganglionic eminence after E10.5 may negatively regulate Nkx2.1 dependent specification of oligodendrocytes. Therefore, both integrative and antagonistic interactions between homeodomain-containing transcription factors contribute to the patterning of the telencephalon.

Animals↗

PubMed1999

Comparison of dynamic and integrated light-scattering techniques in the study of the interaction of Candida rugosa lipase with DPPC liposomes.

Dynamic light-scattering (DLS) and wide angle integrated light-scattering (WAILS) spectroscopies were evaluated in the study of binding of Candida rugosa lipase (CRL) with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes. The use of cumulants analysis on DLS data allowed for the determination of general lipase-liposome-binding trends. Particle intensity distributions obtained from DLS data by a discrete inversion method revealed the different populations created upon lipase-liposome interactions. Using a discrete inversion technique on WAILS data, not only these populations could be differentiated but also accurate number distributions were obtained in short periods of time. Both DLS and WAILS are excellent tools for the study of lipase binding to lipid vesicles; however, care must be exercised in the analysis of the experimental data whenever particle size distributions are multimodal. The selection of the light scattering technique will depend on the information required.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2026

Searching the druggable genome using large language models.

SUMMARY: The druggable genome encompasses the genes that are known or predicted to interact with drugs. The Drug-Gene Interaction Database (DGIdb) provides an integrated resource for discovering and contextualizing these interactions, supporting a broad range of research and clinical applications. DGIdb is currently accessed through structured web interfaces and API calls, requiring users to translate natural-language questions into database-specific query patterns. To allow for the use of DGIdb through natural language, we developed the DGIdb Model Context Protocol (MCP) server, which allows large language models (LLMs) access to up-to-date information through the DGIdb API. We demonstrate that the MCP server improves an LLM's ability to answer questions requiring accurate, up-to-date biomedical knowledge drawn from structured external resources. AVAILABILITY AND IMPLEMENTATION: The DGIdb MCP server is detailed at https://github.com/dgidb/dgidb-mcp-server and includes instructions for accessing the server through the Claude desktop app.

Large Language Models↗

PubMed2026

Searching the Druggable Genome using Large Language Models.

SUMMARY: The druggable genome encompasses the genes that are known or predicted to interact with drugs. The Drug-Gene Interaction Database (DGIdb) provides an integrated resource for discovering and contextualizing these interactions, supporting a broad range of research and clinical applications. DGIdb is currently accessed through structured web interfaces and API calls, requiring users to translate natural-language questions into database-specific query patterns. To allow for the use of DGIdb through natural language, we developed the DGIdb Model Context Protocol (MCP) server, which allows large language models (LLMs) access to up-to-date information through the DGIdb API. We demonstrate that the MCP server greatly enhances an LLM's ability to answer questions requiring accurate, up-to-date biomedical knowledge drawn from structured external resources. AVAILABILITY AND IMPLEMENTATION: The DGIdb MCP server is detailed at https://github.com/griffithlab/dgidb-mcp-server and includes instructions for accessing the server through the Claude desktop app.

Journal Article↗

PubMed2006

Efflux transporters as a novel herbivore countermechanism to plant chemical defenses.

The recent discovery of efflux transporters in the gut has revolutionized our understanding of the absorption and bioavailability of pharmaceuticals and other xenobiotics in humans. Despite the celebrity of efflux transporters in the areas of pharmacology and medicine, their significance is only beginning to be realized in the area of plant-herbivore interactions. This review integrates reports on the importance of gut efflux transporters to diet selection by herbivores. The diets of herbivores are laden with toxic plant secondary metabolites (PSMs) that until recently were thought to be processed almost exclusively by detoxification enzymes in the liver. We describe how efflux transporters in the gut may play a critical role in regulating the absorption of PSMs in herbivores and dictating diet selection. Recent studies suggest that the role of efflux transporters in mediating diet selection in herbivores may be as critical as detoxification enzymes. In addition to diet selection, gut efflux transporters have implications for other aspects of plant-animal interactions. They may be significant components of the evolutionary arms race that influences chemical diversity in plants. Furthermore, in agricultural systems, gut efflux transporters may play an important role in the effectiveness of pesticides. This synthesis paper introduces a new direction in plant-herbivore interactions by providing a complementary mechanism, regulated absorption, to detoxification that may define tolerance to PSMs by herbivores.

Animals↗

PubMed2005

The hypothalamic integrator for circadian rhythms.

Although the suprachiasmatic nucleus (SCN) is well established as providing a genetically based clock for timing circadian rhythms, the mechanisms by which the timing signal is translated into circadian rhythms of behavior and underlying physiology have only recently come to light. The bulk of the SCN outflow terminates in a column of tissue that arches upward and backward from the SCN, and which includes the subparaventricular zone (SPZ) and the dorsomedial nucleus of the hypothalamus. Neurons within the dorsal SPZ are necessary for organizing circadian rhythms of body temperature, whereas neurons in the ventral SPZ are needed for circadian rhythms of sleep and waking. Ventral SPZ neurons in turn relay to the dorsomedial nucleus, which is crucial for producing circadian rhythms of sleep and waking, locomotor activity, feeding and corticosteroid production. This multistage processor provides the animal with flexibility so that environmental cues, such as food availability, ambient temperature and social interactions, can be integrated with the clock signal to sculpt an adaptive pattern of rhythmic daily activities that maximize the chances of survival and reproduction.

Animals↗

PubMed2006

Chromosomal integration of LTR-flanked DNA in yeast expressing HIV-1 integrase: down regulation by RAD51.

HIV-1 integrase (IN) is the key enzyme catalyzing the proviral DNA integration step. Although the enzyme catalyzes the integration step accurately in vitro, whether IN is sufficient for in vivo integration and how it interacts with the cellular machinery remains unclear. We set up a yeast cellular integration system where integrase was expressed as the sole HIV-1 protein and targeted the chromosomes. In this simple eukaryotic model, integrase is necessary and sufficient for the insertion of a DNA containing viral LTRs into the genome, thereby allowing the study of the isolated integration step independently of other viral mechanisms. Furthermore, the yeast system was used to identify cellular mechanisms involved in the integration step and allowed us to show the role of homologous recombination systems. We demonstrated physical interactions between HIV-1 IN and RAD51 protein and showed that HIV-1 integrase activity could be inhibited both in the cell and in vitro by RAD51 protein. Our data allowed the identification of RAD51 as a novel in vitro IN cofactor able to down regulate the activity of this retroviral enzyme, thereby acting as a potential cellular restriction factor to HIV infection.

Chromosomes, Fungal↗

PubMed1995

Integration of an Epstein-Barr virus episome 3' into the gene encoding immunoglobulin heavy-chain alpha 1 in a lymphoblastoid cell line.

For the first time we have characterized an unoccupied site of Epstein-Barr (EBV) virus integration in a lymphoblastoid cell line, RGN1. The site of integration is about 1.5 kb downstream from the gene encoding the heavy chain constant alpha 1, specifying immunoglobulin A (IgA). Sequence and Southern analysis allowed us to hypothesize that integration occurred via a double exchange involving the viral latent origin of DNA replication (oriP) and the human DNA. The region involved in the integration is transcribed into poly(A)+ RNA in all the tested lymphoid lines, but not in the RGN1 line. We suggest a mechanism of integration primed by interactions between oriP and cell ori and its potential role in the establishment and/or evolution of EBV-carrying lines.

B-Lymphocytes↗