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At least 613 records · Page 34Linked to original sources
PubMed1998

Functional diversity of synaptic AMPA/KA receptors from rat as revealed by subtype-specific antagonists.

Subtype-specific pharmacological compounds represent important tools to identify the molecular components of synaptically activated glutamate receptors in central neurones. Here, we utilized a collection of subtype-specific antagonists and modulators to investigate the functional profile of glutamate receptors in identified synapses in thin slices of the cerebellum, hippocampus and brain stem. During whole-cell patch-clamp recordings alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/kainate (AMPA/KA) receptor-mediated synaptic currents (EPSCs) in cerebellar Purkinje cells were (i) prolonged by 100 microM cyclothiazide, (ii) not significantly changed after preincubation in 10 microM concanavalin A, (iii) not affected by 1 microM Evans Blue or polyamine toxin analogue N-(4-hydroxyphenylpropanolyl)-spermine (NHPPS), but (iv) significantly reduced by high (> or = 100 microM) concentrations of Evans Blue. These pharmacological properties were distinct from those observed in hippocampal granule cells and brain stem interneurones and markedly different from those of recombinant glutamate receptor channels GluR1-GluR6 previously investigated in heterologous expression systems.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1996

Impact of the prostatic apex on continence and urinary flow in patients with intestinal neobladders.

OBJECTIVE: To determine the impact of preserving the prostatic apex on continence and urinary flow in patients with post-cystectomy intestinal bladder substitutes. PATIENTS AND METHODS: A total of 38 male patients underwent radical cystectomy for bladder carcinoma and construction of a neobladder from ileum [9], sigmoid [9] or an ileocaecal segment [20]. The intestinal reservoir was anastomosed to the membranous urethra in 25 patients and to the apical prostatic capsule in 13. A subjective evaluation of urinary continence, uroflowmetry and urethral pressure profilometry were performed 1-3 years after surgery. RESULTS: The only variable which showed a significant difference between patients with and without preservation of the prostatic apex was the functional profile length (P < 0.05). Conversely, there was no statistically significant difference in the continence result, peak flow rate and maximum urethral pressure between these two groups. However, there was a significant difference (P < 0.05) in peak flow rate among the three versions of neobladder in patients with a preserved prostatic apex (9.4 mL/s in ileal vs 15.8 mL/s in sigmoid and ileocaecal segments). CONCLUSION: Preservation of the prostatic apex does not improve urinary continence in patients with intestinal neobladders and may present an element obstructing the evacuation of ileal bladders.

Adult↗
PubMed1998

Soluble interleukin 2 receptor in dialyzed patients.

Azotemic patients are usually characterized by a state of so-called preactivation resulting in excessive expression of interleukin 2 receptors (IL-2R) on T lymphocytes. The etiological mechanism of this preactivation is, however, still speculative. We studied the serum level of the soluble form of IL-2R (sIL-2R) in azotemic patients on either hemodialysis (HD) (n = 49) or continuous ambulatory peritoneal dialysis (CAPD) (n = 45). Both patient groups had significantly higher sIL-2R levels (1,750+/-664 U/ml in the HD group and 1,769+/-647 U/ml in the CAPD group, respectively) p < 0.00001 as compared to the normal control group (511+/-436 U/ml). However, there was no significant difference between the levels of the HD and CAPD group patients. When clinical parameters were studied for their influence on sIL-2R levels, none of the following caused any significant changes: blood transfusion, type of dialyzer used, type of dialysis fluid used, treatment with erythropoietin, hepatitis B infection, or liver function profile. We conclude that chronic renal failure per se is the major cause of the preactivation of T lymphocytes. The modes of treatment and various clinical variables in these patients have no significant influence on sIL-2R levels.

Adult↗
PubMed2001

Dynamic analysis of the QT interval in long QT1 syndrome patients with a normal phenotype.

AIMS: In families with the long QT syndrome penetrance may be low: up to 70% of gene carriers may have a normal QTc interval. These patients require therapy, similar to that in those with longer QTc intervals, but identifying them, using molecular analysis, is difficult to apply on a large scale. A large French family affected by the long QT1 syndrome was followed-up over a 25-year period. In adult males but not in females, the QTc interval normalized after puberty. We aimed to find clinical criteria, based on ambulatory ECG recordings so that we could improve diagnosis in affected members with a normal QTc. METHODS AND RESULTS: Linkage analysis and direct sequencing were an indicator of the long QT1 gene in our family. Reverse transcription-polymerase chain reaction analysis demonstrated abnormal transcripts in lymphocytes from silent gene carriers. The functional profile of mutated protein isoforms was investigated using the patch-clamp technique. Dynamic analysis of ventricular depolarization was conducted using Holter recordings in patients, and in sex- and age-matched controls. Circadian variations of the QTc interval and the QT/RR relationship were assessed. Sensitivity, specificity, and predictive values were evaluated for proposed clinical criteria. We found that dynamic analysis of the QT interval permitted individual diagnosis in mutation carriers even when the QTc interval was normal (adult males). CONCLUSION: Dynamic analysis of the QT interval is of diagnostic value in the long QT1 syndrome in patients with a normal phenotype. Clinical implications include improvement in screening and patient management.

Adolescent↗
PubMed1995

Mapping of single amino acid residues required for selective activation of Gq/11 by the m3 muscarinic acetylcholine receptor.

Each G protein-coupled receptor can interact only with a limited number of the many structurally similar G proteins expressed within a cell. This study was undertaken to identify single amino acids required for selectively coupling the m3 muscarinic acetylcholine receptor to G proteins of the Gq/11 family. To this goal, distinct intracellular segments/amino acids of the m3 receptor were systematically substituted into the structurally closely related m2 muscarinic receptor, which couples to Gi/o proteins, not Gq/11 proteins. The resultant mutant receptors were expressed in COS-7 cells and studied for their ability to induce agonist-dependent stimulation of phosphatidylinositol hydrolysis, a response known to be mediated by G proteins of the Gq/11 class. Using this approach, we were able to identify four amino acids in the second intracellular loop and four amino acids at the C terminus of the third intracellular loop of the m3 muscarinic receptor that are essential for efficient Gq/11 activation. We could demonstrate that these amino acids, together with a short segment at the N terminus of the third intracellular loop, fully account for the G protein coupling preference of the m3 muscarinic receptor. Taken together, our data strongly suggest that only a limited number of amino acids, located on different intracellular regions, are required to determine the functional profile of a given G protein-coupled receptor.

Amino Acid Sequence↗
PubMed2003

Do middle ear muscles trigger attacks of Menière's disease?

OBJECTIVE: Current surgical methods for treating Ménière's disease (MD), e.g. endolymphatic sac surgery, mastoidectomy or insertion of middle ear ventilation tubes, only improve vertigo and fail to influence the hearing threshold. In this retrospective study we examined the long-term effects of tenotomy on the symptoms of MD. MATERIAL AND METHODS: A total of 45 patients suffering from definite MD underwent middle ear muscle tenotomy, a treatment that is very rarely considered nowadays. Of these 45 patients, 20 were observed postoperatively for a period of > 2 years. The disease was scored pre- and postoperatively and the results were evaluated according to the American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing and Equilibrium guidelines for the diagnosis and evaluation of therapy for MD. RESULTS: Sectioning of the tensor tympani and stapedius muscle tendons significantly reduced the frequency and intensity of vertigo and improved both the functional profile and tinnitus. Pure-tone audiometry at frequencies between 500 and 3000 Hz substantiated the improvement in hearing threshold, as did the pure-tone average. The therapeutical outcome was stable in cases where both tendons remained persistently disconnected. Intratympanal inflammatory reactions were observed in most patients during surgery. CONCLUSION: Our results prove that tenotomy is a successful and enduring therapeutic approach for treating the auditory and vestibular symptoms of MD and strongly suggest that it should be reconsidered as a promising surgical treatment for the symptoms of MD.

Adult↗
PubMed2006

Patterns of immune response to a vaccine or virus as measured by intracellular cytokine staining in flow cytometry: hypothesis generation and comparison of groups.

Candidate HIV vaccines must show an immune response in order to be considered for further testing and development. What constitutes a "response," however, is still not clear. While the hunt for a protective vaccine continues, hypotheses are being formed by studying the immune responses across cohorts of people with differing responses to the infection, as well as the immune responses formed by healthy people to other viruses, ones that are generally common and well controlled. Here we examine the functional profile of the immune responses of a group of HIV+ long-term non-progressors as measured by intracellular cytokine staining using polychromatic flow cytometry, and compare these responses to those of a larger group of other HIV+ people. We describe some of the types of patterns in immune response that are of interest to vaccine researchers, and compare several statistical tests appropriate for this type of data.

AIDS Vaccines↗
PubMed2006

Effect of fumonisins on macrophage immune functions and gene expression of cytokines in broilers.

Fumonisin (FB1), a mycotoxin, is produced by Fusarium moniliforme and F. proliferatum. A prevalence survey in Taiwan by our laboratory showed that there was a contamination rate of 40% in domestic animal feeds, and the average contaminated level was 4.5 mg/kg. Ninety-six birds were allotted into four treatments fed with diets containing 0 (control), 5, 10, or 15 mg/kg of FB1 for three weeks. The results showed that the growth performance was not influenced by the FB1 challenge, but relative bursa weight was significantly decreased. The activity of serum aspartate aminotransferase, and the serum levels of albumin and cholesterol were significantly elevated by the FB1 challenges. When broilers were stimulated with injection of lipopolysaccharides, mRNA abundance (determined by semi-quantitative RT-PCR) interleukin-1beta (IL-1beta), IL-2, interferon-alpha (IFN-alpha), IFN-gamma, and inducible nitric oxide synthase (iNOS) reached a plateau at 3 h, and declined at 6 h. A FB1 challenge for three weeks increased cytokine mRNA abundance in broilers. The results also showed that 15 mg FB1 per kg feed significantly inhibited the expression of IL-1beta, IL-2, IFN-alpha, IFN-gamma, but had no effect on iNOS. The macrophage functional profile was significantly changed under an exposure of 15 mg FB1 per kg for three weeks. Taken together, our results suggest that FB1 up to 15 mg/kg does not affect growth performance, but impairs some parameters of blood biochemistry and the immunocompetence in broilers.

Animal Feed↗
PubMed1993

Production and characterization of an Mls-1-specific monoclonal antibody.

Superantigens (SAGs) represent a new class of antigens, characterized as T cell receptor (TCR) V beta-reactive elements. Bacterial toxins constitute the major group of exogenous SAGs, while the mouse mammary tumor virus (MMTV)-encoded Mls molecules represent the endogenous SAGs. Mls-1 is the prototype of the latter SAGs, because it elicits a very potent T cell stimulatory response in vitro in unprimed T cells expressing the TCR V beta 6 or 8.1 chains. In vivo, Mls-1 causes deletion of immature T cells bearing the V beta 6, 7, 8.1, or 9 chains. Although Mls-1 was functionally discovered > 20 yr ago, it has not been possible to raise antibodies against this molecule. We have previously cloned and sequenced the Mtv-7 sag gene, which encodes Mls-1. Sequence comparisons with other MMTV sag genes suggested that the polymorphic 3' end encodes the TCR V beta specificity of these SAGs. We have, therefore, immunized hamsters with a 14-amino acid peptide from the deduced COOH-terminal sequence of the Mtv-7 sag gene. We describe here the production of a monoclonal antibody (mAb), 3B12, which is peptide specific and reacts with a recombinant baculovirus product of Mtv-7 sag. This mAb blocks Mls-1-specific T cell recognition and detects the Mls-1 protein on the surface of the B cell hybridoma LBB.A, but not on LBB.11, which is an Mtv-7 loss variant of LBB.A. Transfection of the Mtv-7 sag gene into LBB.11 renders this cell functionally Mls-1+ as well as positive for 3B12 binding, confirming the specificity of this mAb. It is well documented that B cells and CD8+ T cells express T cell stimulatory Mls-1 determinants, and we show here that this functional profile correlates with the expression of MMTV-specific mRNA. However, primary lymphocytes derived from Mls-1+ mice do not stain with 3B12, even after in vitro activation with mitogens or phorbol ester.

Amino Acid Sequence↗
PubMed2006

Toll-like receptor agonists influence the magnitude and quality of memory T cell responses after prime-boost immunization in nonhuman primates.

There is a remarkable heterogeneity in the functional profile (quality) of T cell responses. Importantly, the magnitude and/or quality of a response required for protection may be different depending on the infection. Here, we assessed the capacity of different Toll like receptor (TLR)-binding compounds to influence T helper cell (Th)1 and CD8+ T cell responses when used as adjuvants in nonhuman primates (NHP) with HIV Gag as a model antigen. NHP were immunized with HIV Gag protein emulsified in Montanide ISA 51, an oil-based adjuvant, with or without a TLR7/8 agonist, a TLR8 agonist, or the TLR9 ligand cytosine phosphate guanosine oligodeoxynucleotides (CpG ODN), and boosted 12 wk later with a replication-defective adenovirus-expressing HIV-Gag (rAD-Gag). Animals vaccinated with HIV Gag protein/Montanide and CpG ODN or the TLR7/8 agonist had higher frequencies of Th1 responses after primary immunization compared to all other vaccine groups. Although the rAD-Gag boost did not elevate the frequency of Th1 memory cytokine responses, there was a striking increase in HIV Gag-specific CD8+ T cell responses after the boost in all animals that had received a primary immunization with any of the TLR adjuvants. Importantly, the presence and type of TLR adjuvant used during primary immunization conferred stability and dramatically influenced the magnitude and quality of the Th1 and CD8+ T cell responses after the rAD-Gag boost. These data provide insights for designing prime-boost immunization regimens to optimize Th1 and CD8+ T cell responses.

Adjuvants, Immunologic↗
PubMed2006

FIRST: Fast Iterative Reconstruction Software for (PET) tomography.

Small animal PET scanners require high spatial resolution and good sensitivity. To reconstruct high-resolution images in 3D-PET, iterative methods, such as OSEM, are superior to analytical reconstruction algorithms, although their high computational cost is still a serious drawback. The higher performance of modern computers could make iterative image reconstruction fast enough to be viable, provided we are able to deal with the large number of probability coefficients for the system response matrix in high-resolution PET scanners, which is a difficult task that prevents the algorithms from reaching peak computing performance. Considering all possible axial and in-plane symmetries, as well as certain quasi-symmetries, we have been able to reduce the memory requirements to store the system response matrix (SRM) well below 1 GB, which allows us to keep the whole response matrix of the system inside RAM of ordinary industry-standard computers, so that the reconstruction algorithm can achieve near peak performance. The elements of the SRM are stored as cubic spline profiles and matched to voxel size during reconstruction. In this way, the advantages of 'on-the-fly' calculation and of fully stored SRM are combined. The on-the-fly part of the calculation (matching the profile functions to voxel size) of the SRM accounts for 10-30% of the reconstruction time, depending on the number of voxels chosen. We tested our approach with real data from a commercial small animal PET scanner. The results (image quality and reconstruction time) show that the proposed technique is a feasible solution.

Algorithms↗
PubMed2025

GRUMB: a genome-resolved metagenomic framework for monitoring urban microbiomes and diagnosing pathogen risk.

SUMMARY: Urban infrastructure hosts dynamic microbial communities that complicate biosurveillance and AMR monitoring. Existing tools rarely combine genome-resolved reconstruction with ecological modeling and batch-aware analytics tailored to infrastructure-scale studies. We present GRUMB (Genome-Resolved Urban Microbiome Biosurveillance), an open-source, SLURM-compatible pipeline that reconstructs high-quality metagenome-assembled genomes (MAGs) from shotgun sequencing reads and integrates taxonomic/functional annotation (CARD, VFDB), batch-aware normalization, ecological diagnostics and machine learning classification of environment types with uncertainty and risk scoring. GRUMB accepts either SRA project accessions or paired-end FASTQ files with metadata, and produces assemblies, MAGs, taxonomic and functional profiles, ecological outputs and risk-informed classification. Its modular design enables reproducible, infrastructure-scale biosurveillance across diverse environments. AVAILABILITY AND IMPLEMENTATION: GRUMB is freely available under the MIT License at: https://github.com/SuleimanAminu/genome-resolved-urban-microbiome-biosurveillance; Zenodo DOI: https://doi.org/10.5281/zenodo.15505402. Requirements: Linux (Ubuntu 20.04+), Python 3.11, R 4.2+, SLURM. Issues and feature requests are tracked on GitHub.

Microbiota↗
PubMed2003

The binding interface database (BID): a compilation of amino acid hot spots in protein interfaces.

SUMMARY: To make information about protein interactive function easily accessible, we are mining the primary scientific literature for detailed data about protein interfaces. The Binding Interface Database (BID) organizes the vast amount of protein interaction information into tables, graphical contact maps and descriptive functional profiles. Currently data on 170 interacting protein pairs are available with over 1300 mutations described. AVAILABILITY: The BID database is freely available at http://tsailab.org/BID/ To have your protein of interest entered, contact Tiffany Fischer (tiffbrink@neo.tamu.edu) or Jerry Tsai at the email below

Amino Acid Sequence↗
PubMed2005

Physiological dissociation in hippocampal subregions in response to amygdala stimulation.

Previous studies indicated that the amygdala, when activated by emotional or electrical stimulation, modulates hippocampal-dependent memory processes and synaptic plasticity. Although the modulatory effect of the amygdala has often been generalized to the hippocampal formation, studies suggest that hippocampal subregions may display distinct functional profiles and may respond distinctively to amygdala activation. In this study we assessed the effect of basolateral amygdala (BLA) stimulation on long-term potentiation (LTP)--a synaptic model of memory--induced by a standard (sdTS) or a strong theta stimulation (sgTS) in the hippocampal dentate gyrus (DG) and CA1, in anesthetized rats. The modulatory stimulation was applied 30 s before or after the tetanus stimulation. Results show that while BLA activation impaired CA1 LTP induced with an sdTS, it enhanced LTP in the DG under both sdTS and sgTS conditions. These findings provide evidence for a differential amygdalar control of hippocampal memory subsystems, and may contribute to the understanding of the complexity of memory processes under stressful conditions.

Amygdala↗
PubMed2004

Identification of genes expressed in primate primordial oocytes.

BACKGROUND: The factors involved in oocyte survival and transition from quiescence to the growing phenotype remain unknown. Herein we report genes that are differentially expressed in the primordial oocyte revealed by DNA arrays. METHODS: Primordial oocytes were captured selectively in rhesus monkey ovary sections using laser capture microdissection. The RNA was extracted and amplified in two rounds by T7-based linear RNA amplification, fluorescence labelled and then hybridized to human cDNA arrays containing 7680 elements. RNA from human placenta served as a reference sample. RESULTS: Ninety-five genes were found to be consistently expressed at a higher level in primordial oocytes. Expression of several of these genes in the oocyte has been reported before, e.g. deleted in azoospermia (DAZ), prohibitin and transglutaminase 2. Oocyte expression of several novel transcripts revealed on array hybridization, such as gene 33, ubiquitin-conjugating enzyme E2A, G1 to S phase transition 1, growth arrest and DNA damage-inducible (GADD), and dendritic cell-derived ubiquitin-like protein (DC-UbP) was confirmed by in situ hybridization. Some array-identified gene products [integrin beta3, alpha-tubulin, regulatory telomere elongation protein (RAP1) and cellular repressor of EIA-stimulated genes (CREG protein)] were detected in human oocytes by immunofluorescence. Bioinformatic analysis of the oocyte-enriched transcripts reveals a functional profile summarized as follows: cell cycle (14%); transporter (13%); signal transduction (10%); cytoskeletal (7%); transcription factor (5%); immune response (5%); apoptosis-related (5%); RNA processing (5%); and the remainder of miscellaneous categories. CONCLUSIONS: These observations may contribute to the elucidation of molecular pathways involved in oocyte survival and maturation.

Animals↗
PubMed2025

Native edaphoclimatic regions shape soil communities of crop wild progenitors.

Unveiling the soil biological communities ecologically associated with crop wild progenitors (CWPs) in their habitats of origin is essential for advancing productive and sustainable agriculture. A field survey was conducted to investigate the edaphoclimatic conditions and soil bacterial, fungal, protist, and invertebrate communities of 125 populations of direct progenitors of major crops for world agriculture. The wild populations clustered into four ecoregions shaped by two edaphoclimatic dimensions: one summarizing variations in soil sand contents and nutrients concentrations, and the other featuring changes in aridity, soil pH, and carbon storage potential. We identified a common soil core community across CWPs that varied significantly along deserts to tropical seasonal forests and savannas. The assembly of the soil core community was driven by varying environmental preferences amongst soil biodiversity kingdoms, reflecting potential shifts in their functional profiles. The tropical ecoregion exhibited higher proportion of acidophilic bacteria, fungal, and protist parasites, whilst desert ecosystems harboured greater abundances of saprophytic fungi and heterotrophic protists. Moreover, CWPs displayed unique microhabitats that incorporate variability into the soil community assembly. Our work reveals the biogeography of soil communities associated with CWPs, the first step towards the development of microbial rewilding initiatives.

centres of origin↗
PubMed2004

MUSCLE: multiple sequence alignment with high accuracy and high throughput.

We describe MUSCLE, a new computer program for creating multiple alignments of protein sequences. Elements of the algorithm include fast distance estimation using kmer counting, progressive alignment using a new profile function we call the log-expectation score, and refinement using tree-dependent restricted partitioning. The speed and accuracy of MUSCLE are compared with T-Coffee, MAFFT and CLUSTALW on four test sets of reference alignments: BAliBASE, SABmark, SMART and a new benchmark, PREFAB. MUSCLE achieves the highest, or joint highest, rank in accuracy on each of these sets. Without refinement, MUSCLE achieves average accuracy statistically indistinguishable from T-Coffee and MAFFT, and is the fastest of the tested methods for large numbers of sequences, aligning 5000 sequences of average length 350 in 7 min on a current desktop computer. The MUSCLE program, source code and PREFAB test data are freely available at http://www.drive5. com/muscle.

Algorithms↗
PubMed2005

Recent additions and improvements to the Onto-Tools.

The Onto-Tools suite is composed of an annotation database and six seamlessly integrated, web-accessible data mining tools: Onto-Express, Onto-Compare, Onto-Design, Onto-Translate, Onto-Miner and Pathway-Express. The Onto-Tools database has been expanded to include various types of data from 12 new databases. Our database now integrates different types of genomic data from 19 sequence, gene, protein and annotation databases. Additionally, our database is also expanded to include complete Gene Ontology (GO) annotations. Using the enhanced database and GO annotations, Onto-Express now allows functional profiling for 24 organisms and supports 17 different types of input IDs. Onto-Translate is also enhanced to fully utilize the capabilities of the new Onto-Tools database with an ultimate goal of providing the users with a non-redundant and complete mapping from any type of identification system to any other type. Currently, Onto-Translate allows arbitrary mappings between 29 types of IDs. Pathway-Express is a new tool that helps the users find the most interesting pathways for their input list of genes. Onto-Tools are freely available at http://vortex.cs.wayne.edu/Projects.html.

Animals↗