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At least 1,711 records · Page 95Linked to original sources
PubMed2002

Chromosome localization analysis of genes strongly expressed in human visceral adipose tissue.

To understand fully the physiologic functions of visceral adipose tissue and to provide a basis for the identification of novel genes related to obesity and insulin resistance, the gene expression profiling of human visceral adipose tissue was established by using cDNA array. The characterization and chromosome localization of 400 expressed sequence tags (ESTs) strongly expressed in visceral adipose tissue were analyzed by searching PubMed, UniGene, the Human Genome Draft Database, and Location Data Base. Two hundred eighty-nine clones were classified into known genes among the 400 ESTs strongly expressed in the tissue. Among them, <20% have been previously reported to be expressed in adipose tissue. The chromosome localization of 389 ESTs strongly expressed in visceral adipose tissue showed that their relative abundance was significantly increased on chromosomes 1, 16, 19, 20, and 22 compared with the expected distribution of the same number of random genes. The intrachromosome distribution of the genes strongly expressed in visceral adipose tissue was concentrated in certain regions, such as 1p36.2-1p36.3, 6p21.3-6p22.1, 19p13.3 and 19q13.1. Among them, the region of 1p36.2-1p36.3 appeared to be specific for visceral adipose tissue. Interestingly, some genes playing an important role in the pathogenesis of insulin signal transduction and adipocyte differentiation, such as tumor necrosis factor-alpha and its receptors; CCAAT/enhancer-binding proteina; and phosphoinositide-3-kinase, regulatory subunit, polypeptide 2 (p85beta), were also localized in the concentrated regions, which may provide clues to identifying novel genes closely related to adipocyte function with potential pathophysiologic implications.

Adipocytes↗
PubMed2003

Spermidine metabolism in parasitic protozoa--a comparison to the situation in prokaryotes, viruses, plants and fungi.

Targeting polyamines of parasitic protozoa in chemotherapy has attracted attention because polyamines might reveal novel drug targets for antiparasite therapies (Müller et al. 2001). The biological function of the triamine spermidine in parasitic protozoa has not been studied in great detail although the results obtained mainly imply three different functions, i.e., cell proliferation, cell differentiation, and biosynthesis of macromolecules. Sequence information from the malaria genome project databases and inhibitor studies provide evidence that the current status of spermidine research has to be extended since enzymes of spermidine metabolism are present in the parasite (Kaiser et al. 2001). Isolation and characterisation of these enzymes, i.e., deoxyhypusine synthase (EC 1.1.1.249) (DHS) and homospermidine synthase (EC 2.5.1.44) (HSS) might lead to valuable new targets in drug therapy. Currently research on spermidine metabolism is based on the deposition of the deoxyhypusine synthase nucleic acid sequence in GenBank while the activity of homospermidine synthase was deduced from inhibitor studies. Spermidine biosynthesis is catalyzed by spermidine synthase (EC 2.5.1.16) which transfers an aminopropyl moiety from decarboxylated S-adenosylmethionine to putrescine. Spermidine is also an important precursor in the biosynthesis of the unusual amino acid hypusine (Wolff et al. 1995) and the uncommon triamine homospermidine in eukaryotes, in particular in pyrrolizidine alkaloid-producing plants (Ober and Hartmann 2000). Hypusine is formed by a two-step enzymatic mechanism starting with the transfer of an aminobutyl moiety from spermidine to the epsilon-amino group of one of the lysine residues in the precursor protein of eukaryotic initiation factor eIF5A by DHS (Lee and Park 2000). The second step of hypusinylation is completed by deoxyhypusine hydroxylase (EC 1.14.9929) (Abbruzzese et al. 1985). Homospermidine formation in eukaryotes parallels deoxyhypusine formation in the way that in an NAD(+)-dependent reaction an aminobutyl moiety is transferred from spermidine. In the case of homospermidine synthase, however the acceptor is putrescine. Thus the triamine homospermidine consists of two symmetric aminobutyl moieties while there is one aminobutyl and one aminopropyl moiety present in spermidine. Here, we review the metabolism of the triamine spermidine with particular focus on the biosynthesis of hypusine and homospermidine in parasitic protozoa, i.e., Plasmodium, Trypanosoma and Leishmania, compared to that in prokaryotes i.e., Escherichia coli, a phytopathogenic virus and pyrrolizidine alkaloid-producing plants (Asteraceae) and fungi.

Animals↗
PubMed2003

Privacy issues in personalized medicine.

Pharmacogenomics is the emerging study of why individuals respond differently to drugs. It aims to replace the current 'one size fits all' therapeutic approach with 'personalized medicine' that will use pharmacogenomic tests to predict drug response. In a simple conceptualization, these tests challenge privacy as a result of two factors: how comprehensive is the test and how is the access to samples or digital information controlled. Point-of-care tests are likely to be limited in scope, fit seamlessly into medical records and do not raise qualitatively new ethical and privacy challenges. In order to define practically relevant pharmacogenomic predictive patterns however, large-scale clinical trials and research on human specimens will be required, resulting in large databases of genomic information. The genomic scans' magnitude, stability, implications to kin and ease of dissemination together represent a qualitatively different challenge compared to traditional, self-limited and often temporally transient medical information.

Employment↗
PubMed2006

Multicolor quantum dots for molecular diagnostics of cancer.

In the pursuit of sensitive and quantitative methods to detect and diagnose cancer, nanotechnology has been identified as a field of great promise. Semiconductor quantum dots are nanoparticles with intense, stable fluorescence, and could enable the detection of tens to hundreds of cancer biomarkers in blood assays, on cancer tissue biopsies, or as contrast agents for medical imaging. With the emergence of gene and protein profiling and microarray technology, high-throughput screening of biomarkers has generated databases of genomic and expression data for certain cancer types, and has identified new cancer-specific markers. Quantum dots have the potential to expand this in vitro analysis, and extend it to cellular, tissue and whole-body multiplexed cancer biomarker imaging.

Animals↗
PubMed2005

Five gonadotrophin-releasing hormone receptors in a teleost fish: isolation, tissue distribution and phylogenetic relationships.

Gonadotrophin-releasing hormone (GnRH) is the main neurohormone controlling gonadotrophin release in all vertebrates, and in teleost fish also of growth hormone and possibly of other adenohypophyseal hormones. Over 20 GnRHs have been identified in vertebrates and protochoordates and shown to bind cognate G-protein couple receptors (GnRHR). We have searched the puffer fish, Fugu rubripes, genome sequencing database, identified five GnRHR genes and proceeded to isolate the corresponding complementary DNAs in European sea bass, Dicentrachus labrax. Phylogenetic analysis clusters the European sea bass, puffer fish and all other vertebrate receptors into two main lineages corresponding to the mammalian type I and II receptors. The fish receptors could be subdivided in two GnRHR1 (A and B) and three GnRHR2 (A, B and C) subtypes. Amino acid sequence identity within receptor subtypes varies between 70 and 90% but only 50-55% among the two main lineages in fish. All European sea bass receptor mRNAs are expressed in the anterior and mid brain, and all but one are expressed in the pituitary gland. There is differential expression of the receptors in peripheral tissues related to reproduction (gonads), chemical senses (eye and olfactory epithelium) and osmoregulation (kidney and gill). This is the first report showing five GnRH receptors in a vertebrate species and the gene expression patterns support the concept that GnRH and GnRHRs play highly diverse functional roles in the regulation of cellular functions, besides the "classical" role of pituitary function regulation.

Amino Acid Sequence↗
PubMed2026

In vitro and in vivo studies on the impact of the familial adenomatous polyposis heterogeneous mutation MUC20-S671C on colorectal carcinogenesis and progression.

BACKGROUND: Familial adenomatous polyposis (FAP) is a hereditary colorectal cancer (CRC). We performed genetic testing on nine FAP patients and identified a recurrent mutation at the 671st site of the MUC20 gene-MUC20-S671C. This mutation has a detection frequency of zero in the 1000 Genomes Project database. Previous studies have demonstrated that MUC20 can promote CRC progression through epithelial-mesenchymal transition (EMT). We conducted a series of experiments to analyze the impact of this mutation on CRC cells, aiming to infer its potential role and significance in CRC patients. METHODS: We introduced the MUC20-S671C mutation into the CRC SW480 cell line using the CRISPR-Cas9 technique and established a stable cell line carrying this mutation. We then conducted various experiments to assess the effects of this mutation. The Transwell assay was used to evaluate cell invasion and migration. We also examined cell proliferation, cell cycle progression, and apoptosis rate. Furthermore, we tested the tumorigenic ability of these cells in NOD-scid IL2R&#x3b3;[null] (NSG) mice. Additionally, transcriptome sequencing was performed on both cell lines and mouse tumor tissues to obtain molecular regulatory network data, and key molecules were further validated. RESULTS: The results of Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and colony formation assays indicated that the proliferation ability of mutant cells was significantly reduced. The Transwell assay demonstrated a marked decline in the invasion and migration capabilities of mutant cells. Flow cytometry analysis revealed that the mutation increased the apoptosis rate of CRC cells and might have caused S-phase arrest. The tumor formation assay in nude mice showed that the tumorigenic ability of mutant cells was weakened. Transcriptome sequencing of both the cells and tumor tissues suggested that the mutation altered the expression of apoptosis- and cell cycle-related molecules and also affected EMT. Further experiments confirmed that key molecules involved in the EMT process, such as E-cadherin, were upregulated, while Vimentin, MMP9, and MMP14 were significantly downregulated, indicating that the mutation weakened the EMT capability of CRC cells. CONCLUSIONS: We have identified a novel mutation, MUC20-S671C, in patients with FAP. Our study demonstrates that this mutation exerts its tumor-suppressive effect by reversing the EMT process.

MUC20-S671C↗
PubMedDate not supplied

Detection and identification of previously unrecognized microbial pathogens.

Features of a number of important but poorly explained human clinical syndromes strongly indicate a microbial etiology. In these syndromes, the failure of cultivation-dependent microbial detection methods reveals our ignorance of microbial growth requirements. Sequence-based molecular methods, however, offer alternative approaches for microbial identification directly from host specimens found in the setting of unexplained acute illnesses, chronic inflammatory disease, and from anatomic sites that contain commensal microflora. The rapid expansion of genome sequence databases and advances in biotechnology present opportunities and challenges: identification of consensus sequences from which reliable, specific phylogenetic information can be inferred for all taxonomic groups of pathogens, broad-range pathogen identification on the basis of virulence-associated gene families, and use of host gene expression response profiles as specific signatures of microbial infection.

Animals↗
PubMed2026

Crucial role of telomere maintenance-related genes in survival prediction and subtype identification in colorectal cancer.

BACKGROUND: Telomere maintenance-related genes (TMRGs) are implicated in Colorectal cancer (CRC) development, but their prognostic value and clinical relevance remain insufficiently explored. This study aims to develop a TMRG-based prognostic model and elucidate its clinical utility in CRC management. METHODS: The Cancer Genome Atlas database was utilized to download RNA-seq data from 638 CRC and 51 control samples. Differential expressed genes were screened and intersected with 2086 TMRGs, resulting in the identification of 976 TMRGs. Through univariate and multivariate Cox regression analysis, a prognostic model comprising three telomere maintenance-related biomarkers (PDE1B, TFAP2B, and HSPA1A) was developed and validated using an external dataset. By integrating the model risk score with clinical features, a nomogram was constructed to predict the survival outcomes of CRC patients. Additionally, an in-depth investigation of the immuno-infiltration, functional variation and drug sensitivity analysis were performed in two risk subgroups defined by the prognostic model. Finally, the functional significance of PDE1B in CRC cell lines was investigated through MTT assays, cell colony formation assays, transwell assays and flow cytometry. RESULTS: A total of 976 DE-TMRGs were enriched in telomere/DNA replication pathways. A three-gene signature (PDE1B, TFAP2B, and HSPA1A) stratified patients into high- and low-risk groups with divergent survival (AUC >0.60, validated externally). High-risk patients had advanced N/M stages, elevated M0/M2 macrophages, reduced CD4+ memory T cells, and upregulated immune checkpoints. Nomogram integrating risk score, age, and N/M stage accurately predicted 1-/3-/5-year survival. Low-risk patients showed greater 5-fluorouracil sensitivity. PDE1B expression was significantly reduced in CRC tissues and correlated with advanced stages. Functional assays confirmed PDE1B overexpression suppressed proliferation, migration, invasion, and induced apoptosis in CRC cells. CONCLUSION: This study identifies a moderately predictive telomere maintenance-related gene signature as an independent prognostic predictor in CRC. The risk stratification model effectively discriminates patients with distinct survival patterns, tumor microenvironments, and therapeutic responses, while the integrated nomogram offers additional reference information for survival analysis, albeit with only moderate predictive accuracy. These findings indicate telomere maintenance-related gene signature could serve as a preliminary auxiliary risk stratification tool for postoperative CRC patients, PDE1B may also serve as a potential epithelial tumor-suppressor target for future preclinical studies.

PDE1B↗
PubMed2026

Whole-exome Sequencing Identifies Novel Candidate PCNT Variants in a Child With Overlapping MOPD II Features: A Case Report.

A 7-year-old Chinese boy presented with severe postnatal growth failure (height <3rd percentile at age 7 years), global developmental delay, moderate intellectual disability, and characteristic dysmorphic features including hypertelorism, short palpebral fissures, low-set ears, and a broad nasal bridge. A single electrocardiogram demonstrated a borderline corrected QT interval (QTc = 450 ms). No arrhythmias, QT-prolonging medications, electrolyte abnormalities, or relevant family cardiac history were identified. This finding warrants longitudinal cardiology follow-up and should not be interpreted as definitive Long QT syndrome. Whole-exome sequencing identified two novel missense variants in the PCNT gene (NM_006031.5): c.5675A>G (p.Glu1892Gly) in exon 28 and c.9734G>T (p.Arg3245Ile) in exon 45. Both variants were absent from gnomAD, ExAC, the 1000 Genomes Project database, and Chinese population databases, fulfilling ACMG criterion PM2. Although classified as variants of uncertain significance (VUS) because of limited functional evidence and conflicting in silico predictions, the variants occur in a gene associated with primordial dwarfism and are accompanied by partial phenotypic overlap with Microcephalic Osteodysplastic Primordial Dwarfism Type II (MOPD II). However, parental segregation analysis was unavailable; therefore, the variant phase could not be confirmed, and a recessive disease mechanism could not be established. These findings support the presence of candidate PCNT variants in an atypical primordial dwarfism phenotype and illustrate the utility of whole-exome sequencing for generating testable molecular hypotheses in genetically heterogeneous growth disorders. A definitive molecular diagnosis cannot be established at present, and the isolated borderline QTc finding requires further clinical evaluation.

Humans↗
PubMed2001

Cloning and characterization of IL-22 binding protein, a natural antagonist of IL-10-related T cell-derived inducible factor/IL-22.

The class II cytokine receptor family includes the receptors for IFN-alphabeta, IFN-gamma, IL-10, and IL-10-related T cell-derived inducible factor/IL-22. By screening genomic DNA databases, we identified a gene encoding a protein of 231 aa, showing 33 and 34% amino acid identity with the extracellular domains of the IL-22 receptor and of the IL-20R/cytokine receptor family 2-8, respectively, but lacking the transmembrane and cytoplasmic domains. A lower but significant sequence identity was found with other members of this family such as the IL-10R (29%), cytokine receptor family 2-4/IL-10Rbeta (30%), tissue factor (26%), and the four IFN receptor chains (23-25%). This gene is located on chromosome 6q24, at 35 kb from the IFNGR1 gene, and is expressed in various tissues with maximal expression in breast, lungs, and colon. The recombinant protein was found to bind IL-10-related T cell-derived inducible factor/IL-22, and to inhibit the activity of this cytokine on hepatocytes and intestinal epithelial cells. We propose to name this natural cytokine antagonist IL-22BP for IL-22 binding protein.

Amino Acid Sequence↗
PubMed2003

Cutting edge: Monarch-1: a pyrin/nucleotide-binding domain/leucine-rich repeat protein that controls classical and nonclassical MHC class I genes.

Proteins containing a limited number of N-terminal motifs followed by nucleotide-binding domain and leucine-rich repeat regions are emerging as important regulators for immunity. A search of human genome scaffold databases has identified a large family of known and unknown genes, which we have recently called the CATERPILLER (caspase recruitment domain, transcription enhancer, r(purine)-binding, pyrin, lots of leucine repeats) gene family. This work describes the characterization of a new member, Monarch-1. Monarch-1 has four different splice forms due to the differential splicing of leucine-rich repeat motifs. It is expressed in cells of myeloid-monocytic origin. Affymetrix microarrays and small interfering RNA were used to elucidate the downstream effects of Monarch-1 expression in cells including those of myeloid-monocytic origin. These analyses show that Monarch-1 enhances nonclassical and classical MHC class I expression at the level of the promoter, RNA, and protein expression.

Carrier Proteins↗
PubMed2026

Inference of elevated mutation rates and variant effects using 700k exomes.

Genomic sequencing is now widely accessible for genetic diagnostics and is emerging as a component of newborn screening. This technological development generates the need to characterize incoming mutations, create comprehensive datasets of genes causing rare Mendelian disorders, and identify pathogenic variants. Large-scale exome sequencing datasets such as Genome Aggregation Database (gnomAD) have been assembled to help address these challenges. The recent release of gnomAD (v4; n = 730,947) uncovers millions of rare coding variants, many of which have arisen more than once by independent recurrent mutations in the rapidly growing recent human population. Here, we use newly developed theoretical understanding of sampling properties of rare variants to estimate key population genetics parameters of practical importance to human genetics such as demography history, mutation rate, and selection. Solely relying on population data, our method Population Inferred Estimates of Selection (PIES) identifies novel genes with loss-of-function mutational hotspots likely due to selection in spermatogonia. PIES efficiently estimates selection coefficients for heterozygous loss-of-function variants. Combining population genetics inference with variant effect predictors, PIES predicts pathogenic missense mutations and improves variant prioritization for genetic diagnostics and newborn screening.

Journal Article↗
PubMed2001

Identification of a novel human fibroblast growth factor and characterization of its role in oncogenesis.

The fibroblast growth factor (FGF) family of signaling molecules has been implicated in normal developmental and physiological processes, as well as in human malignancy. Using a homology-based genomic DNA mining process, we identified a human gene encoding a novel member of the FGF family, that we designate FGF-20. The FGF-20 cDNA was isolated, and its sequence confirmed the gene prediction. FGF-20 is expressed in normal brain, particularly the cerebellum, and in some cancer cell lines. Recombinant FGF-20 protein induces DNA synthesis in a variety of cell types and is recognized by multiple FGF receptors. Ectopic expression of FGF-20 in NIH 3T3 cells renders the cells transformed in vitro and tumorigenic in nude mice. These results underscore the utility of mining genomic DNA databases and reveal FGF-20 to be a novel oncogene that may play a role in human cancer.

3T3 Cells↗
PubMed2001

The use of constitutively active receptors for drug discovery at the G protein-coupled receptor gene pool.

Several lines of evidence over the last decade have established that G protein-coupled receptors (GPCRs) can signal in the absence of their natural ligand which results in ligand-independent or constitutive activity. Natural genetic mutation, overexpression and site-directed mutagenesis all result in constitutive activation of GPCRs. Of the 100 leading pharmaceutical products in 2000, 39, wholly or in part, acted through a GPCR-mediated mechanism, a fact that underlines the extreme importance of GPCRs as pharmaceutical drug targets. In addition, the sequencing of the human genome and database mining has revealed that there are hundreds of putative orphan GPCRs for which the natural ligands have not been identified. These orphan GPCRs have largely been inaccessible to drug discovery because traditional methods have mainly relied on ligand-dependent binding assays to discover and pharmacologically characterize potential drug candidates from this receptor class. In the absence of ligand identification, constitutively active receptors allow for a logical and direct way forward through the drug discovery pathway by providing the tool necessary to find modulators of this receptor class in a ligand-independent fashion.

Animals↗
PubMedDate not supplied

Human synthetic peptide vaccine for contraception targeting sperm.

A vaccine targeting sperm is an interesting approach to contraception. The acceptability of a sperm antigen for contraceptive vaccine development is contingent upon its sperm-specificity, surface expression for antibody binding, and involvement in fertilization. Sperm-zona pellucida (ZP) binding is a pivotal step and constitutes an attractive site for immunointerception. Using phage display technology, we have identified a novel dodecamer peptide sequence, designated as YLP(12), that is present on sperm, and is involved in ZP binding and sperm capacitation/acrosome reaction in man/mouse. Extensive search in the human and mouse genome sequence databases did not indicate a complete identity with the YLP(12) nucleotide sequence. It is peptide mimetic with sperm receptor carbohydrate mimicking action that is involved in oocyte binding. The sperm-specific YLP(12) sequence is also involved in involuntary immunoinfertility in men, indicating its autoantigenicity, sperm-specificity, and involvement in fertility/infertility in humans. Vaccination of female animals with synthetic YLP(12) peptide causes a long-term reversible contraception by raising a sperm-specific immune response. The contraceptive effect could also be completely reversed voluntarily at any time by immunoneutralization of antibodies using intravaginal administration of the peptide. Thus, the novel synthetic YLP(12) peptide is an attractive candidate for contraceptive vaccine development, and diagnosis and treatment of immunoinfertility in humans.

Acrosome Reaction↗
PubMed2004

[Cloning and expression of a homologue of human macrophage migration inhibitory factor from P. falciparum 3D7].

OBJECTIVE: To clone and express a homologue of human macrophage migration inhibitory factor (MIF) from P. falciparum 3D7--PfMIF. METHODS: The nucleotide sequence of PfMIF was found through blast P. falciparum genomic sequence databases with the amino acid sequence of human MIF (HuMIF). RT-PCR, DNA sequencing, and bioinformatics analysis were used for the cloning of Pfmif gene. The recombinant protein was expressed in E. coli and purified through the affinity column. RESULTS: The full length of Pfmif gene was cloned and sequenced. It was composed of 351 nucleotides and encoded 116 amino acids with the typical characteristic of MIF family. The recombinant protein was successfully expressed and purified. CONCLUSIONS: The Pfmif gene and recombinant protein were successfully isolated and PfMIF was preliminarily identified as a novel member of MIF family.

Amino Acid Sequence↗
PubMed2004

A novel human G protein-coupled receptor is over-expressed in prostate cancer.

G protein-coupled receptors (GPCRs) are involved in a large variety of physiological functions. The number of known members that belong to this large family of receptors has been rapidly increasing. Now, with the availability of the human genome sequence databases, further family members are being identified. We describe the identification of a novel GPCR that shows no significant amino acid identity to any one of the known members of the GPCR superfamily. The gene expression pattern of this receptor is restricted: in normal tissues it is confined to the nervous system and testis, but we also detected gene expression in several tumor types, most notably prostate cancer, suggesting a potential role for this gene as a marker for this disease.

Amino Acid Sequence↗
PubMed1998

Proclass protein family database: new version with motif alignments.

ProClass is a protein family database which organizes non-redundant sequence entries into families defined collectively by the ProSite patterns and PIR superfamilies. The database consists of about 100,000 entries, more than half of which are classified in about 3,000 families. The new version includes links to various protein family/domain and structural class databases and contains gapped motif alignments for all ProSite patterns. The motif sequences are retrieved from both SwissProt and PIR-international databases, including numerous new members detected by our GeneFIND family identification system. The motif collection represents a 50% increase from those catalogued in ProSite. The ProClass database can be used to maximize family information retrieval, help organize protein sequence databases, and support full-scale genomic annotation. The database and its query program are freely available for on-line record retrieval and direct file transfer from our WWW server at http:/(/)diana.uthct.edu/proclass.html+ ++.

Amino Acid Sequence↗