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At least 1,531 records · Page 85Linked to original sources
PubMed2001

Factors regulating the cytotoxic activity of the human natural killer cell line, NK-92.

NK-92, a highly cytotoxic, interleukin-2 (IL-2)-dependent human natural killer (NK) cell line, has been of interest for basic and translational research. We report on a comprehensive analysis of NK-92 for factors implicated in NK cytotoxicity to elucidate factors underlying NK-92's high cytolytic activity and target range. Thus, we hope to develop a method to identify patients best suited to NK-92 immunotherapy. In addition, as a model system, we hope to increase understanding of the basis for the elevated activity exhibited by activated NK (ANK) cells. NK-92 exhibits an unusual receptor expression profile, expressing a relatively large number of activating (NKp30, NKp46, 2B4, NKGD, E, CD28) receptors. Conversely, it expresses few inhibitory receptors (NKGA/B, low levels of KIR2DL4, ILT-2), lacking most of the killer inhibitory receptors (KIRs) clonally expressed on normal NK cells. In addition, NK-92 expresses high levels of molecules involved in the perforin-granzyme cytolytic pathway as well as additional cytotoxic effector molecules including tumor necrosis factor (TNF)-superfamily members FasL, TRAIL, TWEAK, TNF-alpha, indicating the ability to kill via alternative mechanisms. NK-92 also expresses other molecules implicated immune effector cell regulation (CD80, CD86, CD40L, TRANCE) whose relevance in NK killing is unclear. This study provides initial data to develop a method to identify NK-92 susceptible cells (cells expressing ligands for NK-92 activating receptors ie CD48 for 2B4 and CD80/86 for CD28). Furthermore, this work suggests mechanisms that may contribute to ANK cell activity, including modulation of receptor expression to favor activation, up-regulation of cytotoxic effector molecules, and acquisition of new cytolytic pathways.

Cell Adhesion Molecules↗
PubMed2006

Establishing reporting standards for metabolomic and metabonomic studies: a call for participation.

Metabolite concentrations in cellular systems are very much dependent on the physiological, environmental, and genetic status of an organism and are regarded as the ultimate result of cellular regulation, resulting in the visible phenotypes. Therefore, the comprehensive analysis of metabolite levels and fluxes renders a suitable tool for assessing the degree of perturbation in biological systems. Lessons derived from development of other OMICS areas (genomics, proteomics, and transcriptomics) have shown that large-scale comparisons and interpretations will require the re-use of data over long periods of time and by multiple laboratories with different expertise and backgrounds. Reaching this goal will require standardization of reporting structures of metabolomic studies for journal publication purposes, for regulatory deposition, and for database dissemination. An initiative by the Metabolomics Society is presented that aims to define important aspects of metabolomic workflows. These include biological study designs, chemical analysis, and data processing, as well as the ontologies that are necessary in this framework.

Animals↗
PubMed1999

Monomorphic teratoma of the ovary: a rare cause of triiodothyronine toxicosis.

A case of low thyroid radioactive iodine uptake (RAIU) thyrotoxicosis due to a large struma ovarii comprising pure thyroid tissue is presented, including a detailed diagnostic evaluation, histopathology, and demonstration of rapid recovery of native thyroid function after surgical excision. In addition, the first comprehensive analysis of thyroglobulin obtained from an ovarian struma is reported.

Aged↗
PubMed2002

High-resolution dissection of phagosome maturation reveals distinct membrane trafficking phases.

Molecular mechanisms of endocytosis in the genetically and biochemically tractable professional phagocyte Dictyostelium discoideum reveal a striking degree of similarity to higher eukaryotic cells. Pulse-chase feeding with latex beads allowed purification of phagosomes at different stages of maturation. Gentle ATP stripping of an actin meshwork entrapping contaminating organelles resulted in a 10-fold increase in yield and purity, as confirmed by electron microscopy. Temporal profiling of signaling, cytoskeletal, and trafficking proteins resulted in a complex molecular fingerprint of phagosome biogenesis and maturation. First, nascent phagosomes were associated with coronin and rapidly received a lysosomal glycoprotein, LmpB. Second, at least two phases of delivery of lysosomal hydrolases (cathepsin D [CatD] and cysteine protease [CPp34]) were accompanied by removal of plasma membrane components (PM4C4 and biotinylated surface proteins). Third, a phase of late maturation, preparing for final exocytosis of undigested material, included quantitative recycling of hydrolases and association with vacuolin. Also, lysosomal glycoproteins of the Lmp family showed distinct trafficking kinetics. The delivery and recycling of CatD was directly visualized by confocal microscopy. This heavy membrane traffic of cargos was precisely accompanied by regulatory proteins such as the Rab7 GTPases and the endosomal SNAREs Vti1 and VAMP7. This initial molecular description of phagocytosis demonstrates the feasibility of a comprehensive analysis of phagosomal lipids and proteins in genetically modified strains.

Adenosine Triphosphate↗
PubMed2003

Beyond expression profiling: next generation uses of high density oligonucleotide arrays.

In the past decade, microarray technology has become a major tool for high-throughput comprehensive analysis of gene expression, genotyping and resequencing applications. Currently, the most widely employed application of high-density oligonucleotide arrays (HDOAs) involves monitoring changes in gene expression. This application has been carried out in a variety of organisms ranging from Escherichia coli to humans. The recent near completion of the human and mouse genome sequences, however, as well as the genomes of other model experimental species, has allowed for novel applications of HDOAs, such as: the discovery of novel transcripts, mapping functionally important genomic regions and identifying functional domains in RNA molecules. Integrating all this information will provide novel global views of the locations of RNA transcription, DNA replication and the protein nucleic acid interactions that regulate these processes.

DNA Replication↗
PubMed2004

Differential proteomics: an overview of gel and non-gel based approaches.

The comprehensive analysis of gene expression in complex biological systems has demanded the development of new technologies to study the cell transcriptome and the cell proteome. Each approach has advantages and disadvantages from both the conceptual and the methodological viewpoints. Differential proteomics, the comparison of distinct proteomes (eg normal versus diseased cells, diseased versus treated cells etc) is of paramount importance. Several approaches can be used and these typically involve electrophoresis and/or chromatography combined with chemical or metabolic labelling and mass spectrometry. These approaches aim to identify molecular targets, namely proteins, involved in different physiopathological states. Incorporating this knowledge with knowledge from other technologies lays the foundations of active principles at the molecular level. Here, the various gel- and non-gel-based approaches that are used in a wide range of biological systems for the study of differentially expressed proteins will be reviewed.

Algorithms↗
PubMed2005

Mathematical models of cell cycle regulation.

The cell division cycle is a fundamental process of cell biology and a detailed understanding of its function, regulation and other underlying mechanisms is critical to many applications in biotechnology and medicine. Since a comprehensive analysis of the molecular mechanisms involved is too complex to be performed intuitively, mathematical and computational modelling techniques are essential. This paper is a review and analysis of recent approaches attempting to model cell cycle regulation by means of protein-protein interaction networks.

Algorithms↗
PubMed2025

CREMSA: compressed indexing of (ultra) large multiple sequence alignments.

MOTIVATION: Recent viral outbreaks motivate the systematic collection of pathogenic genomes in order to accelerate their study and monitor the apparition/spread of variants. Due to their limited length and temporal proximity of their sequencing, viral genomes are usually organized, and analyzed as oversized Multiple Sequence Alignments (MSAs). Such MSAs are largely ungapped, and mostly homogeneous on a column-wise level but not at a sequential level due to local variations, hindering the performances of sequential compression algorithms. RESULTS: In order to enable an efficient handling of MSAs, including subsequent statistical analyses, we introduce CREMSA (Column-wise Run-length Encoding for MSAs), a new index that builds on sparse bitvector representations to compress an existing or streamed MSA, all the while allowing for an expressive set of accelerated requests to query the alignment without prior decompression. Using CREMSA, a 65 GB MSA consisting of 1.9M SARS-CoV 2 genomes could be compressed into 22 MB using less than half a gigabyte of main memory, while executing access requests in the order of 100 ns. Such a speed up enables a comprehensive analysis of covariation over this very large MSA. We further assess the impact of the sequence ordering on the compressibility of MSAs and propose a resorting strategy that, despite the proven NP-hardness of an optimal sort, induces greatly increased compression ratios at a marginal computational cost. AVAILABILITY AND IMPLEMENTATION: CREMSA is freely accessible at https://gitlab.univ-lille.fr/cremsa/cremsa. The Snakemake workflow for the benchmarks is available at: https://gitlab.univ-lille.fr/cremsa/bench. The data used in the paper is on Zenodo at https://zenodo.org/records/14698859 and https://zenodo.org/records/15100011.

SARS-CoV-2↗
PubMed2025

DiCARN-DNase: enhancing cell-to-cell Hi-C resolution using dilated cascading ResNet with self-attention and DNase-seq chromatin accessibility data.

MOTIVATION: The spatial organization of chromatin is fundamental to gene regulation and essential for proper cellular function. The Hi-C technique remains the leading method for unraveling 3D genome structures, but the limited availability of high-resolution (HR) Hi-C data poses significant challenges for comprehensive analysis. Deep learning models have been developed to predict HR Hi-C data from low-resolution counterparts. Early Convolutional Neural Network (CNN)-based models improved resolution but struggled with issues like blurring and capturing fine details. In contrast, Generative Adversarial Network (GAN)-based methods encountered difficulties in maintaining diversity and generalization. Additionally, most existing algorithms perform poorly in cross-cell line generalization, where a model trained on one cell type is used to enhance HR data in another cell type. RESULTS: In this work, we propose Dilated Cascading Residual Network (DiCARN) to overcome these challenges and improve Hi-C data resolution. DiCARN leverages dilated convolutions and cascading residuals to capture a broader context while preserving fine-grained genomic interactions. Additionally, we incorporate DNase-seq data into our model, providing a robust framework that demonstrates superior generalizability across cell lines in HR Hi-C data reconstruction. AVAILABILITY AND IMPLEMENTATION: DiCARN is publicly available at https://github.com/OluwadareLab/DiCARN.

Chromatin↗
PubMed2025

HI-FEVER: a Nextflow pipeline for the high-throughput discovery and annotation of endogenous viral elements.

SUMMARY: Endogenous viral elements (EVEs) offer valuable insights into virus and host evolution, but their detection remains computationally and biologically challenging. We present HI-FEVER, a user-friendly Nextflow pipeline for the discovery of EVEs in eukaryotic host genomes. HI-FEVER is highly parallelizable and customizable, ensuring computational efficiency while allowing researchers to fine-tune parameters to their specific needs. Its output provides a comprehensive analysis of discovered EVEs, including detailed annotations which can provide evolutionary insights. HI-FEVER scales seamlessly to handle millions of viral protein queries across multiple host genomes on both laptops and high-performance computing nodes. AVAILABILITY AND IMPLEMENTATION: The HI-FEVER source code is available on GitHub at https://github.com/PaleovirologyLab/hi-fever. Minimal reference databases, test datasets and benchmarking results are hosted on the Open Science Framework at https://osf.io/y357r. A detailed wiki is available at https://github.com/PaleovirologyLab/hi-fever/wiki, including usage instructions, parameter descriptions, and guidance on interpreting outputs. The pipeline includes a Pixi environment compatible with Conda and Apptainer containerization, and Docker images. HI-FEVER has been tested on Linux, Windows (via WSL2), and macOS (Intel and ARM64).

Software↗
PubMed2026

SEMPLR: an R package for transcription factor binding prediction.

SUMMARY: SEMPLR is an R package that predicts transcription factor binding and variant effects using SNP Effect Matrices (SEMs), providing efficient, genome-wide scoring, enrichment testing, and visualization tools for comprehensive analysis of regulatory sequences. AVAILABILITY: Available on GitHub at https://github.com/grkenney/SEMPLR and on Bioconductor at https://bioconductor.org/packages/release/bioc/html/SEMPLR.html.

Transcription Factors↗
PubMed2003

Pyranose oxidase identified as a member of the GMC oxidoreductase family.

Fungal pyranose oxidase is a flavoenzyme whose preferred substrate among several monosaccharides is D-glucose. After a comprehensive analysis of conserved features in a structure-based multiple sequence alignment of homologous proteins, we could classify this enzyme into the GMC oxidoreductase family. The identified homology also suggests a three-dimensional protein structure similar to the functionally related glucose oxidase.

Amino Acid Sequence↗
PubMed2006

HiRes--a tool for comprehensive assessment and interpretation of metabolomic data.

UNLABELLED: The increasing role of metabolomics in system biology is driving the development of tools for comprehensive analysis of high-resolution NMR spectral datasets. This task is quite challenging since unlike the datasets resulting from other 'omics', a substantial preprocessing of the data is needed to allow successful identification of spectral patterns associated with relevant biological variability. HiRes is a unique stand-alone software tool that combines standard NMR spectral processing functionalities with techniques for multi-spectral dataset analysis, such as principal component analysis and non-negative matrix factorization. In addition, HiRes contains extensive abilities for data cleansing, such as baseline correction, solvent peak suppression, removal of frequency shifts owing to experimental conditions as well as auxiliary information management. Integration of these components together with multivariate analytical procedures makes HiRes very capable of addressing the challenges for assessment and interpretation of large metabolomic datasets, greatly simplifying this otherwise lengthy and difficult process and assuring optimal information retrieval. AVAILABILITY: HiRes is freely available for research purposes at http://hatch.cpmc.columbia.edu/highresmrs.html

Algorithms↗
PubMed2000

Cortical connections of the insular and adjacent parieto-temporal fields in the cat.

We present a comprehensive analysis of the cortical connections of the insular and adjacent cortical areas in the domestic cat by using microinjections of wheat-germ agglutinin conjugated to horseradish peroxidase. We examined the identity and extent of the cortical fields connected to each area, the relative anatomical weights of the various connections, their laminar origin, and their paths across the cerebral commissures. Our main finding is that despite their relatively small size and close apposition, the connections of the insular and adjacent areas are far more widespread and more specific to each area than previously realized, suggesting that each area is involved in disparate aspects of cortical integration. The granular insular area is linked to a constellation of somatosensory, motor, premotor and prefrontal districts. The dysgranular insular area is chiefly associated with lateral prefrontal and premotor, lateral somatosensory and perirhinal cortices. The dorsal agranular insular area is connected with limbic neocortical fields, while the ventral agranular insular area is associated with an array of olfactory allocortical fields. The anterior sylvian area is associated with visual, auditory and multimodal areas, with the dorsolateral prefrontal cortex, and with perirhinal area 36. The parainsular area is linked to non-tonotopic auditory and ventromedial frontal areas. Trajectories followed by the callosal axons of each of the investigated areas are extremely divergent. As a whole, the picture of the insular region that emerges from this and a parallel study (Clascá et al., J Comp Neurol 384:456-482, 1997) is that of an extreme heterogeneity, both in terms of histological architecture and neural connections. Comparison with earlier published reports on primates suggests that most, but not all, of the areas we investigated in cats may have an direct counterpart within the insula of Old World monkeys.

Afferent Pathways↗
PubMed1996

Sequence features surrounding the translation initiation sites assigned on the genome sequence of Synechocystis sp. strain PCC6803 by amino-terminal protein sequencing.

To characterize the sequence features surrounding the translation initiation sites on the genome of Synechocystis sp. strain 6803, the total proteins extracted from the cell were resolved by two-dimensional electrophoresis, and the amino-terminal sequences of the relatively abundant protein spots were determined. By comparison of the determined amino-terminal sequences with the nucleotide sequence of the entire genome, the translation initiation sites of a total of 72 proteins were successfully assigned on the genome. The sequence features emerged from the nucleotide sequences at and surrounding the translation initiation sites were as follows: (1) In addition to the three initiation codons, ATG, GTG, and TTG, evidence was obtained that ATT was also used as a rare initiation codon; (2) the core sequences (GAGG, GGAG and AGGA) of the Shine-Dalgarno sequence were identified in the appropriate position preceding the 35 initiation sites (48.6%); and (3) the preferential sequence surrounding the initiation codons was formulated as 5'-YY[...]R-3' where Y and R denote pyrimidine and purine nucleotides, respectively, and three dots represent the initiation codons. The result obtained would provide valuable information for improvement of the gene-finding software, and the approach used in this study should be applicable for comprehensive analysis of the expression profiles of cellular proteins.

Amino Acid Sequence↗
PubMed2000

Generation of 7137 non-redundant expressed sequence tags from a legume, Lotus japonicus.

For comprehensive analysis of genes expressed in a model legume, Lotus japonicus, a total of 22,983 5' end expressed sequence tags (ESTs) were accumulated from normalized and size-selected cDNA libraries constructed from young (2 weeks old) plants. The EST sequences were clustered into 7137 non-redundant groups. Similarity search against public non-redundant protein database indicated that 3302 groups showed similarity to genes of known function, 1143 groups to hypothetical genes, and 2692 were novel sequences. Homologues of 5 nodule-specific genes which have been reported in other legume species were contained in the collected ESTs, suggesting that the EST source generated in this study will become a useful tool for identification of genes related to legume-specific biological processes. The sequence data of individual ESTs are available at the web site: http://www.kazusa.or.jp/en/plant/lotus/EST/.

Codon↗
PubMed2002

Genome-wide profiling of gene expression in 29 normal human tissues with a cDNA microarray.

We have performed a comprehensive analysis of the expression profiles in 25 adult and 4 fetal human tissues by means of a cDNA microarray consisting of 23,040 human genes. This study revealed a number of genes that were expressed specifically in each of those tissues. Among the 29 tissues examined, 4,080 genes were highly expressed (at least a five-fold expression ratio) in one or only a few tissues and 1,163 of those were expressed exclusively (more than a ten-fold higher expression ratio) in a particular tissue. Expression of some of the genes in the latter category was confirmed by northern analysis. A hierarchical clustering analysis of gene-expression profiles in nerve tissues (adult brain, fetal brain, and spinal cord), lymphoid tissues (bone marrow, thymus, spleen, and lymph node), muscle tissues (heart and skeletal muscle), or adipose tissues (mesenteric adipose and mammary gland) identified a set of genes that were commonly expressed among related tissues. These data should provide useful information for medical research, especially for efforts to identify tissue-specific molecules as potential targets of novel drugs to treat human diseases.

Adult↗