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PubMed2026

Prognostic model based on calcium-related genes predicts prognosis and reveals the immune landscape of acute myeloid leukemia.

Acute myeloid leukemia (AML) exhibits heterogeneous outcomes and lacks reliable prognostic markers. As a critical regulator of cell fate, the prognostic value of calcium signaling in AML requires investigation. This study aimed to construct a calcium-related gene (CRG)-based prognostic model for AML. Differential analysis on RNA-seq data was conducted for AML from The Cancer Genome Atlas and Gene Expression Omnibus (GEO). Intersecting differentially expressed genes and CRGs yielded AML-associated differentially expressed CRGs (DECRGs). A prognostic model was developed using univariate/multivariate Cox regression and least absolute shrinkage and selection operator (LASSO) and validated in a GEO dataset. Bioinformatics analyses explored the links between risk groups and immune characteristics, genomic mutations, and drug sensitivity. Key genes' effects on cell proliferation, apoptosis, and differentiation were verified in vitro using CCK-8 assay, colony formation assay, and flow cytometry. The 13-DECRG-based model distinguished high- and low-risk patients in both training and validation cohorts, with high-risk patients showing a worse prognosis. The risk score was an independent prognostic factor. Immune analysis revealed a unique immune microenvironment for the high-risk group. CAMK2A overexpression inhibited cell proliferation and colony-forming ability, promoted cell apoptosis, and induced an increased proportion of CD11b- and CD14-positive cells. In vitro experiments indicated CAMK2A-induced suppression of AML cells' malignant phenotype by activating the P53 signaling pathway. An AML CRG-based model with favorable risk stratification performance was constructed. In vitro experiments revealed CAMK2A-induced inhibition of the malignant phenotype via suppressing proliferation, promoting apoptosis, and facilitating myeloid differentiation in AML cells. This study provides novel evidence for understanding CRGs in AML as well as the potential functions of CAMK2A.

Journal Article↗
PubMed2026

Decreased expression of Krüppel-like factor 4 is associated with colorectal cancer progression.

Krüppel-like factor 4 (KLF4), a key transcription factor,plays an important role in cell proliferation, differentiation, and apoptosis. Here, we explored the prognostic value of KLF4 and its role in colorectal cancer (CRC) progression. We analyzed transcriptomic data and clinical information related to CRC from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. database. Immunohistochemistry was performed to evaluate KLF4 expression in CRC tissue samples. Additionally, we examined the relationship between clinicopathological factors and patient prognosis using Cox proportional hazards model analysis. Lentiviral transfection was used to create KLF4 knockdown HCT-116 cells. Analysis of the TCGA database and two GEO datasets (GSE21510 and GSE117606) revealed that KLF4 was expressed at low levels in CRC. Furthermore, reduced KLF4 levels correlated with lymph node metastasis, distant metastasis, and advanced TNM staging. ROC curve analysis indicated that KLF4 can effectively differentiate cancerous tissue from normal tissue. Functional enrichment analysis identified KLF4 as significantly linked to the glycoprotein metabolic pathway. Our detection of KLF4 expression in CRC tissue samples confirmed its decreased levels and their association with poorer patient survival. However, KLF4 was not identified as an independent prognostic factor. In vitro, KLF4 knockdown promoted HCT-116 cell migration and invasion and downregulated the mRNA expression of glycoprotein synthesis- and glycosylation-related genes. Conversely, KLF4 re-expression markedly reversed these effects. Our findings suggested that low KLF4 expression served as a predictor factor for disease progression in CRC patients. Furthermore, reduced KLF4 levels enhance the migration and invasion of CRC cells, which may be related to impaired glycoprotein metabolism.

Colorectal cancer↗
PubMed2025

Heme oxygenase 1 (HO-1) is a drug target for reversing cisplatin resistance in non-small cell lung cancer.

INTRODUCTION: Platinum-based drugs, the most widely used chemotherapeutic drugs in clinical oncology, have long faced the problem of drug resistance, which is urgently in need of resolution. Identifying biomarkers of drug resistance may help reduce platinum resistance and improve therapeutic efficacy. OBJECTIVES: This study aims to identify potential biomarkers associated with the development of cisplatin resistance in non-small cell lung cancer (NSCLC) and explore mechanisms to overcome chemoresistance. METHODS: NSCLC cisplatin resistance cell lines were constructed, and transcriptome sequencing was performed. Results were validated using Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Molecular docking, proteomics sequencing, and in vitro and in vivo experiments were conducted to evaluate the role of Heme Oxygenase 1 (HO-1) in cisplatin resistance. RESULTS: NSCLC cisplatin resistance cell lines, GEO and TCGA data identified HMOX1, downstream of Nrf2, as a key drug resistance gene induced by cisplatin. Activation of the Nrf2/HO-1 pathway was found to induce ferroptosis resistance, a critical mechanism of cisplatin resistance. Candidate compounds SB 202190 and Nordihydroguaiaretic acid (NDGA) effectively reactivated ferroptosis by inhibiting HO-1, thereby increasing cisplatin sensitivity. CONCLUSION: The Nrf2/HO-1 pathway is a significant contributor to cisplatin resistance in NSCLC. Targeting HO-1 with SB 202190 and NDGA presents a promising strategy to overcome resistance and improve chemotherapy outcomes.

Cisplatin↗
PubMed2025

Genetic predisposition and mediating pathways in ischemic stroke-induced cardiac arrhythmias: a genome-wide analysis.

INTRODUCTION: The clinical presentation of stroke-heart syndrome (SHS) underscores the interplay between the central nervous system and the cardiovascular system. While cardiac arrhythmia is the prevalent form of cardiac injury in SHS patients, the causal link between ischemic stroke and cardiac arrhythmia is still unclear. METHODS: Mendelian randomization analyses and genome-wide association studies data were used to investigate the causal role of ischemic stroke on cardiac complications. Mediation and colocalization analyses were used to identify potential pathways and shared genetic variants. Single nucleotide polymorphisms (SNPs) associated with arrhythmias and ischemic stroke were used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Gene expression omnibus (GEO) database from atrial fibrillation patients were used for validation. RESULTS: Mendelian randomization analyses showed a strong correlation between arrhythmias, including ventricular tachyarrhythmias and atrial fibrillation, with ischemic stroke. Diabetic microvascular (nephropathy, retinopathy) and macrovascular (cardiomyopathy, peripheral arterial disease) complications significantly mediated the effect of ischemic stroke on cardiac arrhythmias and atrial fibrillation, explaining 28.69 % and 20.48 % of the indirect effect, respectively. Colocalization analyses identified a shared causal variant in the Phosphodiesterase 3A (PDE3A) gene (rs11045239), providing genetic evidence for a shared pathogenic pathway between ischemic stroke and cardiac arrhythmias. Moreover, KEGG pathway enrichment analyses identified a role of the cyclic adenosine monophosphate (cAMP) signaling pathway in both ischemic stroke and arrhythmias. Validation using the GEO database confirmed a significant upregulation of the PDE3A gene expression in atrial fibrillation patients. CONCLUSION: This study demonstrated a causal link between ischemic stroke and cardiac arrhythmias, with diabetic complications as one mediating factor. The identification of a shared causal variant in the PDE3A gene and the role of the cAMP signaling pathway have the potential to improve prediction and management of SHS patients.

Humans↗
PubMed2026

Key hub genes and pathways associated with HCV-related hepatocellular carcinoma as potential diagnostic biomarkers.

BACKGROUND: Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) remains a major global health challenge, with high morbidity and mortality despite recent therapeutic advances. Early detection and identification of reliable molecular biomarkers are essential to improve patient outcomes. Therefore, the present study aimed to investigate key hub genes and pathways associated with HCV-related HCC as potential diagnostic biomarkers. METHODS: The datasets GSE69715 and GSE62232 were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were recognized according to an adjusted p-value and a log fold change (logFC). The GEO2R tool facilitated the identification of common DEGs across the two datasets. Pathways were explored using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases. Furthermore, protein-protein interactions (PPIs) were assessed through Cytoscape. The target genes were confirmed through a GEPIA analysis. RESULTS: A total of 421 common DEGs were identified, and 80 hub genes were subsequently determined through GEO and PPI network analyses, respectively. The GO and KEGG pathways analysis presented DEGs were enhanced in metabolic pathways, cellular components, extracellular exosome, detoxification of copper ion and monooxygenase activity. The GEPIA analysis indicated a notable variation in the expression levels of four specific genes -CDKN2A, CDK1, CCNB1, and TOP2A-when comparing normal samples to tumor samples. CONCLUSION: The present study discovered novel genes by expression variation in HCV-related hepatocellular carcinoma development. These findings suggest that CDKN2A, CDK1, CCNB1, and TOP2A are promising candidates for diagnostic biomarkers and present a valuable opportunity for the early identification of HCV-HCC, which could lead to improved treatment outcomes.

Bioinformatics↗
PubMed2006

Compensatory increases in Her-2/neu activation in response to EGFR tyrosine kinase inhibition in colon cancer cell lines.

BACKGROUND: Tyrosine kinase receptors of the ErbB family have become promising targets for anti-neoplastic drugs, but mechanisms of resistance are incompletely understood. To investigate such pathways, we applied a small-molecule, selective EGFR inhibitor, OSI-774, to three well-characterized colon cancer cell lines and studied the alterations of expression and activation of receptors in the erbB family. METHODS: MTT assays were performed to determine the IC(50)s of GEO, FET, and HCT 116 human colorectal cancer cell lines treated with OSI-774. Plated cells were then exposed to either DMSO control or 7 microm of OSI-774 for treatment durations of 1, 3, 5, 7, 10, 14, 28, and 56 days. Cell lysates were evaluated by Western blotting, evaluating both total and phosphorylated levels of EGFR, Her-2/neu, and erbB-3. RESULTS: IC(50) values for GEO, FET, and HCT 116 cell lines exposed to OSI-774 were 12.0, 16.0, and greater than 100 microm, respectively. In all treated cell lines, OSI-774 diminished EGFR activation but did not affect total expression compared with controls. In contrast, Her-2/neu activation was increased in all cell lines. These changes in EGFR and Her-2/neu were identified within 24 h but peaked later in the treatment cycle. ErbB-3 expression and activation did not follow a consistent pattern between cell lines. CONCLUSIONS: Inhibition of EGFR led to increased activation of Her-2/neu. This result suggests a possible mechanism by which cells might escape the proapoptotic signals resulting from EGFR blockade. Our findings suggest concurrent inhibition of multiple members of the erbB family may yield stronger apoptotic responses than single receptor blockade alone.

Apoptosis↗
PubMedDate not supplied

"This food may contain ..." What nurses should know about genetically engineered foods.

Genetic engineering has been in existence since 1973. The process involves placing genetic DNA from one organism into another. Genetically engineered organisms (GEOs) are the name given to such new species of plants created through this process. Proponents of GEOs assert that foods we are now able to produce have greater nutritional value, longer shelf life, better appearance, taste and smell. There are positive benefits to genetic engineering of plants and animals. A growing concern for the health safety of genetically engineered plants and foods is developing among the cautious. The purpose of this article is to define genetic engineering, present benefits and risks, describe the impact on human health, and address implications for nursing.

Consumer Product Safety↗
PubMed2006

The GIS-based SafeAirView software for the concentration assessment of radioactive pollutants after an accidental release.

The European Commission Joint Research Centre (JRC) in Ispra (Italy) has long been running nuclear installations for research purposes. The Nuclear Decommissioning and Facilities Management Unit (NDFM) is responsible for the surveillance of radioactivity levels in nuclear emergency conditions. The NDFM Unit has commissioned the implementation of a specifically developed decision support system, which can be used for quick emergency evaluation in the case of hypothetical accident and for emergency exercises. The requisites were to be a user-friendly software, able to quickly calculate and display values of air and ground radioactive contamination in the complex area around JRC, following an accidental release of radioactive substances from a JRC nuclear research installation. The developed software, named "SafeAirView", is an advanced implementation of GIS technology applied to an existing MS-DOS mode dispersion model, SAFE_AIR (Simulation of Air pollution From Emissions_Above Inhomogeneous Regions). SAFE_AIR is a numerical model which simulates transport, diffusion, and deposition of airborne pollutants emitted in the low atmosphere above complex orography at both local and regional scale, under non-stationary and inhomogeneous emission and meteorological conditions. SafeAirView makes use of user-friendly MS-Windows type interface which drives the dispersion model by a sequential and continuous input-output process, allowing a real time simulation. The GIS environment allows a direct interaction with the territory elements in which the simulation takes place, using data for the JRC Ispra region represented in geo-referenced cartography. Furthermore it offers the possibility to relate concentrations with population distribution and other geo-referenced maps, in a geographic view. Output concentration and deposition patterns can be plotted and/or exported. In spite of the selected specific databases, the SafeAirView software architecture is a general structure, therefore the decision support system could be easily modified to be applied in a region different from the JRC one. Beside the description of SafeAirView, the present paper presents a statistical evaluation of the software, which has considered three well known tracer experiments: Copenhagen, Indianapolis and Kincaid. The data sets related to these experiments are all included in the so called Model Validation Kit.

Data Interpretation, Statistical↗
PubMed2026

Lactylation-related immune-metabolic dysregulation defines prognostic and therapeutic stratification in lung adenocarcinoma.

BACKGROUND: Lactylation links lactate metabolism with inflammatory signaling and immune regulation in tumors. However, its cellular distribution and translational value in lung adenocarcinoma (LUAD) remain unclear. METHODS: Single-cell RNA-sequencing datasets GSE189357 and GSE171145 were integrated to characterize lactylation-related activity, intercellular communication, and malignant epithelial cell states in LUAD. Single-cell-derived lactylation-related differentially expressed genes were mapped to TCGA-LUAD and multiple GEO cohorts. Univariate Cox regression and machine learning algorithms were used to construct a lactylation-related prognostic signature (LRPS). The associations of LRPS with prognosis, immunotherapy response, drug sensitivity, genomic alterations, immune infiltration, and inflammation- and metabolism-related pathways were evaluated. KRT7 was further validated using virtual knockout analysis, spatial transcriptomics, and in vitro and in vivo experiments. RESULTS: lactylation-related transcriptional activity showed heterogeneous distribution across LUAD cell populations and was associated with altered cell-cell communication. In malignant epithelial cells, LRTS-high and LRTS-low states exhibited distinct metabolic, inflammatory, and tumor-related pathway activities. LRPS showed stable prognostic performance in TCGA-LUAD and multiple GEO cohorts and remained an independent prognostic factor. Low LRPS was associated with greater potential benefit from immunotherapy, whereas different LRPS groups displayed distinct drug sensitivity, genomic alteration, and immune microenvironment patterns. KRT7 was highly expressed in LUAD and associated with poor prognosis. KRT7 knockdown suppressed LUAD cell proliferation, migration, invasion, colony formation, and tumor growth in vivo. CONCLUSIONS: This study identifies lactylation-related immune-metabolic dysregulation as a clinically relevant feature of LUAD and develops a single-cell-guided LRPS for prognosis and therapeutic stratification. KRT7 emerged as an LRPS-related functional candidate with experimentally supported roles in malignant LUAD phenotypes.

Immunotherapy↗
PubMed2003

Changes in oligodendrocytes and myelin gene expression after radiation in the rodent spinal cord.

PURPOSE: The aim of this study was to assess changes in oligodendrocytes (OL), myelin gene expression, and their relationships with late demyelination after irradiation. METHODS AND MATERIALS: Adult rats were given single doses of 8 or 22 Gy to the cervical spinal cord. Immunohistochemistry for APC or GST-pi was used to identify OL. Changes in myelin gene expression were assessed using RT-PCR for proteolipid protein (PLP). Luxol fast blue staining was used to assess demyelination. CNP-(beta)geo transgenic mice were used to confirm some of the results of the rat model. Cells of the oligodendroglial lineage in these animals express beta-galactosidase (beta-gal). RESULTS: Early apoptosis of APC, GST-pi, and beta-galactosidase positive cells was observed in the spinal cord of rats and CNP-(beta)geo mice. At 24 h after 22 Gy, there was a significant decrease in OL density. Cell density continued to decline thereafter after both 8 and 22 Gy, and a reduction in PLP expression was observed at 4-5 weeks. A further decrease in PLP expression was seen beginning at 18 weeks after 22 Gy only. Demyelination was observed at 19 weeks after 22 Gy. CONCLUSIONS: Apoptosis of OL and changes in OL density and PLP gene expression were observed early after both 8 and 22 Gy. This suggests that these early changes are unlikely to be directly related to the late demyelination observed.

Animals↗
PubMed1997

A new retroviral vector, CA1, to identify and select for cells expressing an inserted gene in vitro and in vivo.

A new retroviral vector has been constructed that expresses genes encoding three different activities from a single transcript. This feature has been exploited to enable the efficient marking and selection of cells that express a gene of interest. The marker gene lacZ, encoding beta-galactosidase, and neo, encoding neomycin phosphotransferase, for selection by the antibiotic G418, are expressed as a fusion, beta Geo. The expression of beta Geo is coordinated with expression of a gene of interest at the mRNA level using an Internal Ribosome Entry Site (IRES) from the Encephalomyocarditis Virus (EMCV). The IRES promotes cap-independent initiation of translation therefore two reading frames can be translated from a single transcript. In vitro, the vector has been shown to confer beta-galactosidase activity, transformation by v-src and resistance to G418, following infection of cells. To show that the retrovirus was able to mark infected cells in vivo, cells infected with the retrovirus were transplanted into mouse mammary gland where they grew and were successfully located by staining for beta-galactosidase over 2 months after transplantation.

Animals↗
PubMed2026

Identification of Immune Response-Related Proteomic Biomarkers in Moyamoya Disease Using Serum Olink Proteomics.

Moyamoya disease, a rare chronic cerebrovascular disorder, requires invasive digital subtraction angiography (DSA) for diagnosis. This study employed high-throughput proteomics to identify plasma biomarkers for Moyamoya disease diagnosis. We conducted immunopanel analysis using the Olink platform to evaluate 92 immune-related proteins in plasma samples from 88 Moyamoya disease patients and 88 healthy controls. Key proteins were identified through differential expression analysis, GO, and KEGG enrichment analysis. A diagnostic model was constructed using LASSO regression, Boruta algorithm, and machine learning models including random forest and XGBoost. Validation of these proteins was performed using GEO external data sets, followed by prediction of potential therapeutic drugs and molecular docking validation through pharmacogenomic databases. A total of 44 differentially expressed proteins were identified through the Olink immunopanel, with 12 downregulated and 32 upregulated. GO and KEGG analyses revealed significant enrichment of these proteins in innate immune responses and signaling pathways such as NF-kB and MAPK. Through LASSO, random forest, and protein under-area analysis, four potential biomarkers for Moyamoya disease (MGMT, SIT1, PRDX1, TRAF2) were identified. A diagnostic model using these proteins showed the highest AUC value with the XGBoost model. Additionally, TRAF2 and PRDX1 exhibited significant expression differences in Moyamoya disease patients within the GEO data set. Our study revealed the immune landscape of Moyamoya disease, identified four biomarkers, and established a variety of diagnostic models.

Humans↗
PubMed2006

Anomalous ionic conductivity increase in Li2S + GeS2 + GeO2 glasses.

Numerous studies of the ionic conductivities in oxide-doped chalcogenaide glasses have shown the anomalous result that the ionic conductivity actually increases significantly (by more than a factor of 10 in some cases) by the initial addition of an oxide phase to a pure sulfide glass. After this initial sharp increase, the conductivity then monotonically decreases with further oxide addition. While this behavior is important to the application of these glasses for Li batteries, no definitive understanding of this behavior has been elucidated. To examine this effect further and more completely, the ionic conductivities of 0.5Li(2)S + 0.5[(1 - x)GeS(2) + xGeO(2)] glasses have been measured on disc-type bulk glasses. The ionic conductivity of the 0.5Li(2)S + 0.5GeS(2) (x = 0) glass was observed to increase from 4.3 x 10(-5) (Omega cm)(-1) to 1.5 x 10(-4) (Omega cm)(-1) while the activation energy decreased to 0.358 eV from 0.385 eV by the addition of 5 mol % of GeO(2). Further addition of GeO(2) monotonically decreased the conductivity and increased the activation energy. On the basis of our previous studies of the structure of this glass system, the Anderson and Stuart model was applied to explain the decrease in the activation energy and increase in the conductivity. It is suggested that the "doorway" radius between adjacent cation sites increases slightly (from approximately 0.29(+/-0.05) A to approximately 0.40(+/-0.05) A) with the addition of oxygen to the glass and is proposed to be the major cause in decreasing the activation energy and thereby increasing the conductivity. Further addition of oxides appears to contract the glass structure (and the doorway radius) leading to an increase in the conductivity activation energy and a decrease in the conductivity.

Journal Article↗
PubMed2000

Simultaneous blockage of different EGF-like growth factors results in efficient growth inhibition of human colon carcinoma xenografts.

A majority of human colon carcinomas coexpress the epidermal growth factor (EGF)-related peptides transforming growth factor alpha (TGFalpha), amphiregulin (AR) and CRIPTO-1 (CR). We have synthesized novel, antisense mixed backbone oligonucleotides (AS MBOs) directed against TGFalpha, AR and CR. We screened the EGF-related AS MBOs for their ability to inhibit the anchorage independent growth of GEO human colon carcinoma cells. The MBOs that showed a high in vitro efficacy were then used for in vivo experiments. TGFalpha, AR and CR AS MBOs were able to inhibit the growth of GEO tumor xenografts in nude mice in a dose-dependent manner. Furthermore, the AS MBOs were able to specifically inhibit the expression of the target mRNAs and proteins in the tumor xenografts. A more significant tumor growth inhibition was observed when mice were treated with a combination of the three AS MBOs as compared to treatment with a single AS MBO. Finally, tumors from mice treated with TGFalpha, AR and CR AS MBOs showed a significant reduction of microvessel count, as compared with tumors from untreated mice or from mice treated with a single AS MBO. These data suggest that combinations of AS oligonucleotides directed against different growth factors might represent a novel, experimental therapy approach of colon carcinomas.

Amphiregulin↗
PubMed2002

Autocrine heregulin generates growth factor independence and blocks apoptosis in colon cancer cells.

The aim of this study was to determine whether constitutive ErbB2 activation controls growth and apoptosis in colon cancer cells. Growth arrested GEO cells showed constitutive activation of ErbB2 in the absence of exogenous growth factors or serum supplementation. Higher levels of heregulin and ErbB2 activation were observed in the growth-arrested state and cell cycle re-entry was independent of exogenous growth factors. Blockade of ErbB2 activation by heregulin neutralizing antibodies and by AG879 resulted in prevention of cell cycle re-entry. This indicated that autocrine heregulin activity was responsible for growth factor independence and for cell cycle re-entry. Activation of ErbB2 was the result of heregulin mediated interaction with ErbB3 and generated downstream activation of the ERK and the PI3K/AKT pathways. Heregulin neutralizing antibody treatment of growth arrested GEO cells also generated apoptosis as reflected by PARP cleavage and DNA fragmentation indicating a cell survival signal was also induced by the constitutively activated ErbB2. The activation of AKT but not the MAPK pathway was responsible for cell survival in these cells.

Adenocarcinoma↗
PubMed2003

Inter-individual variability in levels of human microsomal protein and hepatocellularity per gram of liver.

AIMS: To determine levels of microsomal protein (MPPGL) and hepatocellularity (HPGL) per gram of human liver and their interindividual variability. METHODS: Triplicate liver samples were used to determine values of MPPGL (n = 20) and HPGL (n = 7) after accounting for the fractional loss of microsomal protein or hepatocytes during processing. Repeated measurements from each liver sample allowed the estimation of true interindividual variability in MPPGL and HPGL using ANOVA. RESULTS: The value of MPPGL ranged from 26 to 54 mg g(-1) (mean(geo)= 33 mg g(-1)). The value of HPGL ranged from 65 to 185 x 10(6) cells g(-1) (mean(geo)= 10(7) x 10(6) cells g(-1)). CONCLUSIONS: There is significant interindividual variability in MPPGL, which has implications for the accurate extrapolation of in vitro data on drug metabolism to predict in vivo metabolic clearance.

Adult↗
PubMed2001

Deep-Earth reactor: nuclear fission, helium, and the geomagnetic field.

Geomagnetic field reversals and changes in intensity are understandable from an energy standpoint as natural consequences of intermittent and/or variable nuclear fission chain reactions deep within the Earth. Moreover, deep-Earth production of helium, having (3)He/(4)He ratios within the range observed from deep-mantle sources, is demonstrated to be a consequence of nuclear fission. Numerical simulations of a planetary-scale geo-reactor were made by using the SCALE sequence of codes. The results clearly demonstrate that such a geo-reactor (i) would function as a fast-neutron fuel breeder reactor; (ii) could, under appropriate conditions, operate over the entire period of geologic time; and (iii) would function in such a manner as to yield variable and/or intermittent output power.

Earth, Planet↗
PubMed1996

An upstream activator of transcription coordinately increases the level and epigenetic stability of gene expression.

The mouse metallothionein-I (mMT-I) promoter is activated by the metal response element-binding transcription factor (MTF), which binds metal response elements (MREs) when stimulated with heavy metals. We analyzed eight K562 erythroleukemia cell clones, each carrying a single integrated copy of an mMT-I/beta-geo construct, using a system that can independently assess the level of beta-geo expression and the rate at which it is silenced. In these clones, basal expression and rate of silencing vary widely and independently with integration site. This implies that the rates of transcription and of silencing are separate properties determined by interaction of the regulatory elements of the transgene with the site of integration. Induction of the mMT-I promoter with zinc both increases expression level and strongly retards silencing of beta-geo expression. At a given integration site, expression level and silencing are affected coordinately by induction. Taken together with earlier studies of distant metal-responsive elements, these results suggest that distance from the promoter may determine whether a factor can increase transcription rate. Stimulation of an MRE can both increase transcription and overcome repressive effects of chromatin; we suggest that these functions are linked.

Animals↗