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At least 1,693 records · Page 94Linked to original sources
PubMed2003

FarR regulates the farAB-encoded efflux pump of Neisseria gonorrhoeae via an MtrR regulatory mechanism.

The farAB operon of Neisseria gonorrhoeae encodes an efflux pump which mediates gonococcal resistance to antibacterial fatty acids. It was previously observed that expression of the farAB operon was positively regulated by MtrR, which is a repressor of the mtrCDE-encoded efflux pump system (E.-H. Lee and W. M. Shafer, Mol. Microbiol. 33:839-845, 1999). This regulation was believed to be indirect since MtrR did not bind to the farAB promoter. In this study, computer analysis of the gonococcal genome sequence database, lacZ reporter fusions, and gel mobility shift assays were used to elucidate the regulatory mechanism by which expression of the farAB operon is modulated by MtrR in gonococci. We identified a regulatory protein belonging to the MarR family of transcriptional repressors and found that it negatively controls expression of farAB by directly binding to the farAB promoter. We designated this regulator FarR to signify its role in regulating the farAB operon. We found that MtrR binds to the farR promoter, thereby repressing farR expression. Hence, MtrR regulates farAB in a positive fashion by modulating farR expression. This MtrR regulatory cascade seems to play an important role in adjusting levels of the FarAB and MtrCDE efflux pumps to prevent their excess expression in gonococci.

Amino Acid Transport Systems, Neutral↗
PubMed2000

Variable numbers of TTC repeats in Mycobacterium leprae DNA from leprosy patients and use in strain differentiation.

Strain differentiation of Mycobacterium leprae would be of great value for epidemiological investigation to identify the infectious sources of leprosy, to understand transmission patterns, and to distinguish between relapse and reinfection. From the M. leprae genome sequence database, TTC DNA repeats were identified. Primer sets designed to amplify the region flanking TTC repeats revealed PCR products of different sizes, indicating that the number of repeats at each locus may be variable among M. leprae strains. The TTC repeats were not found in Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium marinum, or human tissues, which indicated their specificity to M. leprae. Sequence analysis of the TTC repeat region in each of the M. leprae strains showed a variation of 10 to 37 repeats. In the M. leprae strains of 34 multibacillary patients at Cebu, Philippines, M. leprae with 24 and 25 TTC repeats was most common, and this was followed by strains with 14, 15, 20, 21, and 28 repeats. This study thus indicates that there are variable numbers of TTC repeats in a noncoding region of M. leprae strains and that the TTC region may be useful for strain differentiation for epidemiological investigations of leprosy.

Autoradiography↗
PubMed1996

Identification of baculovirus gene that promotes Autographa californica nuclear polyhedrosis virus replication in a nonpermissive insect cell line.

A gene that promotes Autographa californica M nuclear polyhedrosis virus (AcMNPV) replication in IPLB-Ld652Y cells, a cell line that is nonpermissive for AcMNPV, was identified in Lymantria dispar M nuclear polyhedrosis virus (LdMNPV). Cotransfection of AcMNPV DNA and a plasmid carrying the LdMNPV gene into IPLB-Ld652Y cells results in AcMNPV replication. The gene maps between 43.3 and 43.8 map units on the 162-kbp genome of LdMNPV. It comprises a 218-codon open reading frame and encodes a polypeptide with a predicted molecular mass of 25.7 kDa. The predicted polypeptide is glutamic acid and valine rich and negatively charged, with a pI of 4.61. No protein sequence motifs were identified, and no matches with known nucleotide or peptide sequences were found in the AcMNPV genome or database searches that suggest how this gene might function. A recombinant AcMNPV bearing the LdMNPV gene overcomes a block in protein synthesis observed in AcMNPV-infected IPLB-Ld652Y cells. Using Southern blotting techniques, we were unable to identify a homolog in Orgyia pseudotsugata M nuclear polyhedrosis virus, a baculovirus that is routinely propagated in IPLB-Ld652Y cells. This suggests that the LdMNPV host range is unique among the baculoviruses studied to date. We named this gene hrf-1 (for host range factor 1).

Amino Acid Sequence↗
PubMed2001

Phages of dairy bacteria.

Bacteriophages of lactic acid bacteria are a threat to industrial milk fermentation. Owing to their economical importance, dairy phages became the most thoroughly sequenced phage group in the database. Comparative genomics identified related cos-site and pac-site phages, respectively, in lactococci, lactic streptococci and lactobacilli. Each group was represented with closely related temperate and virulent phages. Over the structural genes their gene maps resembled that of lambdoid coliphages, suggesting distant evolutionary relationships. Despite a lack of sequence similarity, a number of biochemical characteristics of these dairy phages are lambda-like (genetic switch, DNA packaging, head and tail morphogenesis, and integration, but not excision). These dairy phages thus provide interesting variations to the phage lambda paradigm. The structural gene cluster of Lactococcus phage r1t resembled that of phages from mycobacteria. Virulent lactococcal phages with prolate heads (c2-like genus of Siphoviridae), in contrast, have no known counterparts in other bacterial genera.

Animals↗
PubMed2002

Virtual cloning, functional expression, and gating analysis of human connexin31.9.

We have identified a novel gap junction gene by searching the human genome sequence database that encodes a protein designated as connexin31.9 (Cx31.9). Cx31.9 was most homologous to human Cx32.4 and did not cluster with either the purported alpha- or beta-connexin subfamilies. Expression of Cx31.9 was detected by RT-PCR in human mRNA from several tissues including cerebral cortex, heart, liver, lung, kidney, spleen, and testis. A partial Cx31.9 sequence was also represented in the human Expressed Sequence Tag database. Cx31.9 formed intercellular channels in both paired Xenopus oocytes and transfected neuroblastoma N2A cells that were distinguished by an apparent low unitary conductance (12-15 pS) and a remarkable insensitivity to transjunctional voltage. In contrast, Cx31.9 channels were gated by cytoplasmic acidification or exposure to halothane like other connexins. Cx31.9 was able to form heterotypic channels with the highly voltage-sensitive Xenopus Cx38 (XenCx38), which provides an opportunity to study gating in heterotypic channels formed by hemichannels (connexons) composed of connexins with widely divergent properties. Thus Cx31.9 is a novel human connexin that forms channels with unique functional properties.

Adult↗
PubMed2005

Inosine released after hypoxia activates hepatic glucose liberation through A3 adenosine receptors.

Inosine, an endogenous nucleoside, has recently been shown to exert potent effects on the immune, neural, and cardiovascular systems. This work addresses modulation of intermediary metabolism by inosine through adenosine receptors (ARs) in isolated rat hepatocytes. We conducted an in silico search in the GenBank and complete genomic sequence databases for additional adenosine/inosine receptors and for a feasible physiological role of inosine in homeostasis. Inosine stimulated glycogenolysis (approximately 40%, EC50 4.2 x 10(-9) M), gluconeogenesis (approximately 40%, EC50 7.8 x 10(-9) M), and ureagenesis (approximately 130%, EC50 7.0 x 10(-8) M) compared with basal values; these effects were blunted by the selective A3 AR antagonist 9-chloro-2-(2-furanyl)-5-[(phenylacetyl)amino][1,2,4]-triazolo[1,5-c]quinazoline (MRS 1220) but not by selective A1, A2A, and A2B AR antagonists. In addition, MRS 1220 antagonized inosine-induced transient increase (40%) in cytosolic Ca2+ and enhanced (90%) glycogen phosphorylase activity. Inosine-induced Ca2+ mobilization was desensitized by adenosine; in a reciprocal manner, inosine desensitized adenosine action. Inosine decreased the cAMP pool in hepatocytes when A1, A2A, and A2B AR were blocked by a mixture of selective antagonists. Inosine-promoted metabolic changes were unrelated to cAMP decrease but were Ca2+ dependent because they were absent in hepatocytes incubated in EGTA- or BAPTA-AM-supplemented Ca2+-free medium. After in silico analysis, no additional cognate adenosine/inosine receptors were found in human, mouse, and rat. In both perfused rat liver and isolated hepatocytes, hypoxia/reoxygenation produced an increase in inosine, adenosine, and glucose release; these actions were quantitatively greater in perfused rat liver than in isolated cells. Moreover, all of these effects were impaired by the antagonist MRS 1220. On the basis of results obtained, known higher extracellular inosine levels under ischemic conditions, and inosine's higher sensitivity for stimulating hepatic gluconeogenesis, it is suggested that, after tissular ischemia, inosine contributes to the maintenance of homeostasis by releasing glucose from the liver through stimulation of A3 ARs.

Adenosine↗
PubMed2005

Chronic alcohol exposure alters transcription broadly in a key integrative brain nucleus for homeostasis: the nucleus tractus solitarius.

Chronic exposure to alcohol modifies physiological processes in the brain, and the severe symptoms resulting from sudden removal of alcohol from the diet indicate that these modifications are functionally important. We investigated the gene expression patterns in response to chronic alcohol exposure (21-28 wk) in the rat nucleus tractus solitarius (NTS), a brain nucleus with a key integrative role in homeostasis and cardiorespiratory function. Using methods and an experimental design optimized for detecting transcriptional changes less than twofold, we found 575 differentially expressed genes. We tested these genes for significant associations with physiological functions and signaling pathways using Gene Ontology terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, respectively. Chronic alcohol exposure resulted in significant NTS gene regulation related to the general processes of synaptic transmission, intracellular signaling, and cation transport as well as specific neuronal functions including plasticity and seizure behavior that could be related to alcohol withdrawal symptoms. The differentially expressed genes were also significantly enriched for enzymes of lipid metabolism, glucose metabolism, oxidative phosphorylation, MAP kinase signaling, and calcium signaling pathways from KEGG. Intriguingly, many of the genes we found to be differentially expressed in the NTS are known to be involved in alcohol-induced oxidative stress and/or cell death. The study provides evidence of very extensive alterations of physiological gene expression in the NTS in the adapted state to chronic alcohol exposure.

Alcoholism↗
PubMed2001

Novel candidate genes for atherosclerosis are identified by representational difference analysis-based transcript profiling of cholesterol-loaded macrophages.

OBJECTIVES: To analyze the early gene expression in macrophages accompanying the phenotypic changes into foam cells upon exposure to oxidized low-density lipoprotein. To identify candidate genes and markers for further studies into the pathogenesis of atherosclerosis. METHODS: Cells of the monocytic cell line THP-1 were activated by PMA and exposed to oxidized low-density lipoprotein. Gene expression profiles were investigated after 24 h, using a solid phase cDNA representational difference analysis (RDA) method and shotgun sequencing. Results were verified by microarray hybridization, and analyzed in the virtual chip display of a novel software tool for transcript profile exploration. RESULTS: By comparing transcript profiles of exposed/unexposed cells, 1,984 transcript sequences, representing a total of 921 genes with altered expression levels in response to oxidized low-density lipoprotein exposure, were identified. Genes that are central to cell cycle control and proliferation, inflammatory response, and of pathways not previously implicated in atherosclerosis were identified. The data obtained is also made available on-line at http:// biobase.biotech.kth.se/thp1a for further exploration. CONCLUSION: The identification of new candidate genes for atherosclerotic disease through RDA-based transcript profiling facilitates further functional genomic studies in coronary artery disease. Candidate genetic polymorphism markers of potential clinical relevance can be identified by filtering information in genome variation databases through the virtual chip analysis of the transcript profiles and subsequently tested in association studies.

Arteriosclerosis↗
PubMed2006

iHAP--integrated haplotype analysis pipeline for characterizing the haplotype structure of genes.

BACKGROUND: The advent of genotype data from large-scale efforts that catalog the genetic variants of different populations have given rise to new avenues for multifactorial disease association studies. Recent work shows that genotype data from the International HapMap Project have a high degree of transferability to the wider population. This implies that the design of genotyping studies on local populations may be facilitated through inferences drawn from information contained in HapMap populations. RESULTS: To facilitate analysis of HapMap data for characterizing the haplotype structure of genes or any chromosomal regions, we have developed an integrated web-based resource, iHAP. In addition to incorporating genotype and haplotype data from the International HapMap Project and gene information from the UCSC Genome Browser Database, iHAP also provides capabilities for inferring haplotype blocks and selecting tag SNPs that are representative of haplotype patterns. These include block partitioning algorithms, block definitions, tag SNP definitions, as well as SNPs to be "force included" as tags. Based on the parameters defined at the input stage, iHAP performs on-the-fly analysis and displays the result graphically as a webpage. To facilitate analysis, intermediate and final result files can be downloaded. CONCLUSION: The iHAP resource, available at http://ihap.bii.a-star.edu.sg, provides a convenient yet flexible approach for the user community to analyze HapMap data and identify candidate targets for genotyping studies.

Algorithms↗
PubMed2003

The evolution of Runx genes I. A comparative study of sequences from phylogenetically diverse model organisms.

BACKGROUND: Runx genes encode proteins defined by the highly conserved Runt DNA-binding domain. Studies of Runx genes and proteins in model organisms indicate that they are key transcriptional regulators of animal development. However, little is known about Runx gene evolution. RESULTS: A phylogenetically broad sampling of publicly available Runx gene sequences was collected. In addition to the published sequences from mouse, sea urchin, Drosophila melanogaster and Caenorhabditis elegans, we collected several previously uncharacterised Runx sequences from public genome sequence databases. Among deuterostomes, mouse and pufferfish each contain three Runx genes, while the tunicate Ciona intestinalis and the sea urchin Strongylocentrotus purpuratus were each found to have only one Runx gene. Among protostomes, C. elegans has a single Runx gene, while Anopheles gambiae has three and D. melanogaster has four, including two genes that have not been previously described. Comparative sequence analysis reveals two highly conserved introns, one within and one just downstream of the Runt domain. All vertebrate Runx genes utilize two alternative promoters. CONCLUSIONS: In the current public sequence database, the Runt domain is found only in bilaterians, suggesting that it may be a metazoan invention. Bilaterians appear to ancestrally contain a single Runx gene, suggesting that the multiple Runx genes in vertebrates and insects arose by independent duplication events within those respective lineages. At least two introns were present in the primordial bilaterian Runx gene. Alternative promoter usage arose prior to the duplication events that gave rise to three Runx genes in vertebrates.

Amino Acid Sequence↗
PubMed2026

LARS promotes hepatocellular carcinoma progression via the PI3K/AKT/mTOR pathway and interaction with RPS5, and serves as a prognostic biomarker.

BACKGROUND: Hepatocellular carcinoma (HCC) caused many cancer deaths around the world. Its progression involves complex mechanisms, creating an urgent need to identify new therapeutic targets. Leucine-tRNA synthetase (LARS) is a key enzyme for protein synthesis, but its specific role and mechanism in HCC are not well understood. PURPOSE: This research aims to investigate the biological function, molecular mechanism, and clinical relevance of the LARS gene in HCC progression, to assess its potential as a treatment target. METHODS: LARS expression was assessed in HCC cell lines (PLC-PRF-5, HCC-LM3) and in mouse subcutaneous tumor models using siRNA and adeno-associated virus (AAV). Techniques including Cell Counting Kit-8(CCK-8), colony formation, EdU, Transwell, wound healing, and flow cytometry were used to measure cell proliferation, migration, invasion, and apoptosis. RNA-seq, proteomics (TMT), western blot, co-immunoprecipitation (Co-IP) with mass spectrometry, molecular docking, and molecular dynamics simulation were employed to study the affected signaling pathway (PI3K/AKT/mTOR) and interacting protein (RPS5). The TCGA (The Cancer Genome Atlas) database and UALCAN platform were used to analyze links between LARS expression and clinicopathological features or prognosis in HCC patients. RESULTS: Reducing LARS expression significantly inhibited the proliferation, colony formation, migration, and invasion of HCC cells, while promoting apoptosis. In mice, LARS knockdown markedly slowed tumor growth. Mechanistic studies showed that reducing LARS expression levels affected the PI3K/AKT/mTOR signaling pathway and led to decreased levels of the key interacting protein RPS5. Overexpressing RPS5 partly reversed the proliferation inhibition caused by LARS depletion. Molecular docking and dynamics simulations suggested that the environmental contaminant triphenyl phosphate (TPP) might bind to the LARS protein. Clinical data analysis revealed that LARS expression is higher in HCC tissues. High LARS expression was significantly associated with shorter overall survival (OS) in patients and correlated positively with various clinical features like tumor stage, grade, and TP53 mutation status. CONCLUSION: LARS helped HCC become worse by affecting the PI3K/AKT/mTOR pathway and working with RPS5. High LARS meant a worse outcome for patients. This suggested LARS could be used to predict disease or as a treatment target in HCC.

Carcinoma, Hepatocellular↗
PubMed2026

Untargeted-targeted metabolomics: energy metabolism characteristics in heart failure staging and discovery of novel biomarkers.

BACKGROUND: Heart Failure represents the severe stage of various heart diseases. Its global morbidity and mortality are on the rise, making it a serious public health issue that imposes a heavy burden on patients' families and society. Currently, there are relatively few systematic studies on the changes in specific metabolites and pathways in different stages of heart failure, such as Stage A, Stage B and Stage C. AIMS: Using untargeted-targeted metabolomics to explore the metabolic characteristics of Heart Failure, and screen out serum metabolic markers with potential diagnostic and prognostic value. METHODS: This study is a cross-sectional study. A total of 210 heart failure patients from Xiyuan Hospital of China Academy of Chinese Medical Sciences were enrolled between October 2023 and October 2024. Among them, 60 patients were selected for targeted metabolomics analysis via stratified sampling. Serum samples of the patients were collected and pretreated with methanol, then metabolites were detected using untargeted and targeted LC-MS respectively. After the raw data were processed with MSDIAL, pattern recognition was performed using principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). Differential metabolites with variable importance in projection (VIP)&#x2009;>&#x2009;1 and P&#x2009;<&#x2009;0.05 were screened, and relevant pathways were analyzed via enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. RESULTS: Untargeted metabolomics revealed that, compared with patients in Stages A and B, those with heart failure in Stage C had decreased serum levels of alanine, creatine, and branched-chain amino acids, along with increased levels of citric acid, fumaric acid, and malic acid. The differential metabolites were primarily enriched in pathways including the citric acid cycle, central carbon metabolism, and amino acid metabolism, indicating that energy metabolism plays a crucial role in the occurrence and progression of HF. Targeted metabolomics validated the findings from untargeted metabolomics: compared with Stage A, the level of phosphoenolpyruvate in Stage B was reduced; and in comparison with patients in Stage A or B, patients in Stage C showed decreased serum levels of multiple energy metabolites (e.g., glucose-6-phosphate, fructose-6-phosphate, 3-phosphoglyceric acid, AMP, ADP and ATP) as well as increased levels of malic acid, which is consistent with the characteristics of the "hypermetabolism-energy starvation" paradox. CONCLUSION: Stage C of heart failure is characterized by energy metabolism collapse (decreased ATP and TCA compensation), and differential metabolites (such as malic acid) may serve as potential candidate biomarkers pending longitudinal validation.

Humans↗
PubMed2026

Pilea: profiling bacterial growth dynamics from metagenomes with sketching.

BACKGROUND: Quantifying bacteria's growth rates is essential for understanding their ecological roles and for building predictive models in environmental and clinical settings. Peak-to-trough ratios (PTRs) derived from shotgun metagenomes offer a culture-independent proxy for in situ growth rates of bacterial species, yet their reliable computation remains challenging. RESULTS: We introduce Pilea&#xa0;( https://github.com/xinehc/pilea ), an alignment-free, sketching-based method that incorporates statistical models for robust PTR estimation. Pilea achieves speed improvements over existing methods while also enhancing accuracy, as demonstrated on both simulated and real datasets. CONCLUSIONS: By scaling efficiently to comprehensive reference collections such as the Genome Taxonomy Database (GTDB), Pilea enables large-scale analyses of bacterial growth dynamics across biomes, unlocking new insights for ecological research. Video Abstract.

Bacteria↗
PubMed2005

Prokineticins (endocrine gland-derived vascular endothelial growth factor and BV8) in the bovine ovary: expression and role as mitogens and survival factors for corpus luteum-derived endothelial cells.

A highly vascular endocrine gland, the corpus luteum (CL) is an excellent model for the study of angiogenic factors. Prokineticins (PK-1 and -2), also termed endocrine-gland-derived vascular endothelial growth factor (VEGF) and BV8 are newly identified proteins described as selective angiogenic mitogens. We previously identified PK binding sites, two closely homologous G protein-coupled receptors (PK-R1 and PK-R2) in human and bovine ovarian cells, but their function remained unknown. In this study we examined the presence and effects of PK in CL-derived endothelial and steroidogenic cell types (LEC and LSC, respectively). PK-1 mRNA was identified in CL and follicles by real-time PCR, using primers specific for the bovine PK-1 sequence (retrieved from Bos taurus whole genome shotgun database). PK were potent angiogenic mitogens for LEC; they enhanced cell proliferation, elevated [3H]thymidine incorporation, MAPK activation, and c-jun/fos mRNA expression. The effects of PK proteins on cell survival were examined by nuclear morphology (4',6-diamidino-2-phenylindole dihydrochloride staining), measurement of DNA fragmentation (terminal dUTP nucleotide end labeling assay), and caspase-3 cleavage. Results obtained by these techniques demonstrated that PK protected LEC from serum starvation-induced apoptosis. Stress conditions such as serum withdrawal, TNF-alpha, and hypoxia markedly increased PK-R2 expression, whereas mRNA levels of PK-R1 remained unchanged. These suggest that the antiapoptotic effect of PK-1 on LEC may be mediated via PK-R2. PK-1 increased VEGF mRNA expression by LSC, implying that it could also indirectly, via VEGF, affect luteal angiogenesis. Together, these findings suggest an important role for PK-1 in luteal function by acting as a mitogen and survival factor in LEC.

Amino Acid Sequence↗
PubMed2005

Elimination of a long-range cis-regulatory module causes complete loss of limb-specific Shh expression and truncation of the mouse limb.

Mutations in a conserved non-coding region in intron 5 of the Lmbr1 locus, which is 1 Mb away from the sonic hedgehog (Shh) coding sequence, are responsible for mouse and human preaxial polydactyly with mirror-image digit duplications. In the mouse mutants, ectopic Shh expression is observed in the anterior mesenchyme of limb buds. Furthermore, a transgenic reporter gene flanked with this conserved non-coding region shows normal polarized expression in mouse limb buds. This conserved sequence has therefore been proposed to act as a long-range, cis-acting regulator of limb-specific Shh expression. Previous phylogenetic studies have also shown that this sequence is highly conserved among tetrapods, and even in teleost fishes. Paired fins of teleost fishes and tetrapod limbs have evolved from common ancestral appendages, and polarized Shh expression is commonly observed in fins. In this study, we first show that this conserved sequence motif is also physically linked to the Shh coding sequence in a teleost fish, the medaka, by homology search of a newly available genomic sequence database. Next, we show that deletion of this conserved intronic sequence by targeted mutation in the mouse results in a complete loss of Shh expression in the limb bud and degeneration of skeletal elements distal to the stylopod/zygopod junction. This sequence contains a major limb-specific Shh enhancer that is necessary for distal limb development. These results suggest that the conserved intronic sequence evolved in a common ancestor of fishes and tetrapods to control fin and limb development.

Animals↗
PubMed2001

[Identification and characterization of histamine H4 receptor].

Recently, we and other groups have identified cDNA encoding the novel histamine H4 receptor. All of the groups have initially found a clue for the H4 receptor-nucleotides sequence in the human draft genomic DNA database. The primary structure of H4 receptor reveals the highest homology with H3 receptor among known G-protein coupled receptors (37.4%). H4 receptor binds to histamine with high affinity, which results in the down-regulation of intracellular cAMP level. H4 receptor is activated not only by histamine, but also R-(alpha)-methylhistamine (H3 receptor agonist), clobenpropit (H3 receptor antagonist), clozapine (neuroleptic) and other histaminergic compounds, while it is antagonized by thioperamide (H3 receptor antagonist). The H4 receptor is localized in the peripheral blood leukocytes, spleen, thymus, small intestine, colon, bone marrow and so on. The tissue distribution of the H4 receptor and known physiological function of histamine tempts us to speculate about its function as an immune modulator. Although there needs much additional work on characterization of the H4 receptor, the discovery of this receptor subtype will unveil a new phase for determining the physiological role of histamine.

Amino Acid Sequence↗
PubMed2006

Genetic effects of radiation in atomic-bomb survivors and their children: past, present and future.

Genetic studies in the offspring of atomic bomb survivors have been conducted since 1948 at the Atomic Bomb Casualty Commission and its successor, the Radiation Effects Research Foundation, in Hiroshima and Nagasaki. Past studies include analysis of birth defects (untoward pregnancy outcome; namely, malformation, stillbirth, and perinatal death), chromosome aberrations, alterations of plasma and erythrocyte proteins as well as epidemiologic study on mortality (any cause) and cancer incidence (the latter study is still ongoing). There is, thus far, no indication of genetic effects in the offspring of survivors. Recently, the development of molecular biological techniques and human genome sequence databases made it possible to analyze DNA from parents and their offspring (trio-analysis). In addition, a clinical program is underway to establish the frequency of adult-onset multi-factorial diseases (diabetes mellitus, high blood pressure, and cardiovascular disease etc) in the offspring. The complementary kinds of data that will emerge from this three-pronged approach (clinical, epidemiologic, and molecular aspects) promise to shed light on health effects in the offspring of radiation-exposed people.

Abnormalities, Radiation-Induced↗
PubMed2004

Identification of microRNAs and other tiny noncoding RNAs by cDNA cloning.

MicroRNAs (miRNAs) and other small RNAs can be identified by cloning and sequencing cDNAs prepared from the approximately 22-nt fraction of total RNA. Methods are described for the construction of cDNA libraries from small noncoding RNAs through the use of T4 RNA ligase, reverse transcriptase, and polymerase chain reaction. cDNAs are cloned in lambda or plasmid vectors, and the sequences are compared to annotated genomic sequence databases, and analyzed by RNA folding programs to distinguish miRNA sequences from other small RNAs of similar size. Northern blot hybridization is used to confirm the expression of small RNAs in vivo.

3' Untranslated Regions↗