The growth regulatingfactor CTGF/CCN-2 is an integral factor in growth and development, connective tissue maintenance, wound repair and cell cycle regulation. It has recently been reported that CTGF/CCN-2...Full Text Available
Hepatocyte nuclear factor (HNF) 4α is a key transcription factorregulating endo/xenobiotic-metabolizing enzymes and transporters. We investigated whether microRNAs are involved in the regulation...Full Text Available
Erythroid differentiation regulator (Erdr1) was first discovered in mouse leukemia cell lines and functions as a stress-related survival factor. This study investigated whether Erdr1 regulates murine melanoma progression, as well as the mechanism involved in Erdr1-regulated metastasis. The expression of Erdr1 is negatively correlated with IL-18 expression, which has a pro-cancer effect in melanoma. To study the role of Erdr1 as an anti-cancer factor, cell migration, invasion, and proliferation were measured. Erdr1 overexpression markedly inhibited the level of cell migration, invasion, and proliferation in B16F10 cells in vitro. In addition, Erdr1 overexpression significantly suppressed melanoma lung colonization, metastasis, and tumor growth in vivo. To identify the factors ...
Most genetic changes that promote tumorigenesis involve dysregulation of G1 cell cycle progression. A key regulatory site in G1 is a growth factor–dependent restriction point (R) where cells...Full Text Available
p53 plays a critical role in tumor suppression. As a transcription factor, in response to stress signals, p53 regulates its target genes and initiates stress responses, including cell cycle arrest,...Full Text Available
Glucagon plays critical roles in regulating glucose homeostasis, mainly by counteracting the effects of insulin. Consequently, the dysregulated glucagon secretion that is evident in type 2 diabetes has significant implications in the pathophysiology of the disease. Glucagon secretion from pancreatic -cells has been suggested to be modulated by blood glucose, signals from the nervous system and endocrine components. In addition to these regulators, intraislet factors acting in a paracrine manner from neighbouring -cells are emerging as central modulator(s) of -cell biology. One of the most important of these paracrine factors, insulin, modulates glucagon secretion. Indeed, the -cell-specific insulin receptor knockout (IRKO) mouse manifests hypersecretion of glucagon in the postprandial stag...
Hypoxia inducible factor-1 (HIF-1) promotes tumor cell adaptation to microenvironmental stress. HIF-1 is up-regulated in irradiated tumors and serves as a promising target for radiosensitization....Full Text Available
KLF1 regulates a diverse suite of genes to direct erythroid cell differentiation from bipotent progenitors. To determine the local cis-regulatory contexts and transcription factor networks...Full Text Available
... time, sucrase activity, a marker of intestinal epithelium (Matsushita, 1983) was observed in epithelial cells with CdxA ... PubMed, CSAIshii, Y., K. Fukuda, H. Saiga, S. Matsushita, and S. Yasugi. 1997. E...
The role of IGF-I in the negative regulation of GH expression and release is demonstrated by in vitro and in vivo models; however, the targets and mechanisms of IGF-I...Full Text Available
Normal brain development requires a series of highly complex and interrelated steps. This process presents many opportunities for errors to occur, which could result in developmental defects...Full Text Available
Osteoblasts are the primary cells responsible for bone formation. They also support osteoclast formation from bone marrow precursors in response to osteotropic factors by inducing receptor activator...Full Text Available
Transforming growth factor (TGF)-beta isoforms (TGF-beta 1, -beta 2, and -beta 3) regulatecell growth and differentiation and have critical regulatory roles in the process of tissue repair and remodeling....Full Text Available
The cell cycle-regulatory transcription factor E2F-1 is regulated by interactions with proteins such as the retinoblastoma gene product and by cell cycle-dependent alterations in E2F-1 mRNA abundance....Full Text Available
Metastatic disease is a primary cause of cancer-related death, and factors governing tumor cell metastasis have not been fully elucidated. Here, we address this question by using tumor cell lines derived...Full Text Available
Angiotensin II (Ang II) is a key proapoptotic factor in fibrotic tissue diseases. However, the mechanism of Ang-II-induced cell death in endothelial cells has not been previously elucidated....Full Text Available
Cancer cells recruit monocytes, macrophages and other inflammatory cells by producing abundant chemoattractants and growth factors, such as macrophage colony-stimulating factor (M-CSF/CSF-1) and monocyte chemoattractant protein-1 (MCP-1/CCL2), to promote tumor growth and dissemination. An understanding of the mechanisms that target cancer cells and regulate tumor microenvironment is essential in designing anticancer therapies. Here, we showed that serum amyloid-A (SAA) and cathelicidin (LL-37) stimulated M-CSF and MCP-1 expression with or without lipopolysaccharide (LPS) administration; conversely, lipoxin-A4 (LXA4) and annexin-A1 (ANXA1) inhibited LPS-induced M-CSF and MCP-1 production by human (HepG2) and mouse (H22) hepatocellular carcinoma cells (HCCs). The effects of LXA4, ANXA1, SAA ...
sFlt-1 (soluble Flt-1) potently inhibits angiogenesis by binding extracellularly to VEGF (vascular endothelial growth factor). In the present paper, we report that hypoxia down-regulates sFlt-1 expression...Full Text Available
Redd1, a recently discovered stress-response gene, is regulated by hypoxia via hypoxia-inducible factor 1 (HIF-1) and by DNA damage via p53/p63; however, the signaling pathway by which its expression is induced by hypoxia has not been elucidated. We demonstrated that the up-regulation of Redd1 transcription by hypoxia and high cell density (HCD) depends on cooperation between Sp1 and HIF-1#alpha# downstream of the PI3K/Akt pathway.
Autophagy is a regulated catabolic process triggered in cells deprived of nutrients or growth factors that govern nutrient uptake. Here we report that autophagy is induced by cetuximab, a therapeutic...Full Text Available
BackgroundCoiled-coil domain containing 115 (Ccdc115) or coiled coil protein-1 (ccp1) was previously identified as a downstream gene of Fibroblast Growth Factor 2 (FGF2) highly expressed...Full Text Available
Anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL) is an aggressive non-Hodgkin lymphoma of T/null immunophenotype that is most prevalent in children and young adults. The...Full Text Available
The capacity of bones to adjust their mass and architecture to withstand the loads of everyday activity derives from the ability of their resident cells to respond appropriately to the strains engendered....Full Text Available
Vacuolar ion channels in guard cells play important roles during stomatal movement and are regulated by many factors including Ca2+, calmodulin, protein kinases, and phosphatases....Full Text Available
CD44, a transmembrane receptor for hyaluronic acid, is implicated in various adhesion-dependent cellular processes, including cell migration, tumor cell metastasis and invasion. Recent studies demonstrated that CD44 expressed in cancer cells can be proteolytically cleaved at the ectodomain by membrane type 1-matrix metalloproteinase (MT1-MMP) to form soluble CD44 and that CD44 cleavage plays a critical role in cancer cell migration. Here, we show that transforming growth factor-b (TGF-b), a multifunctional cytokine involved in cell proliferation, differentiation, migration and pathological processes, induces MT1-MMP expression in MDA-MB-435s cells. TGF-b-induced MT1-MMP expression was blocked by the specific extracellular regulated kinase-1/2 (ERK1/2) inhibitor PD98059 and the specific pho...
Abstract Plant pathogenic bacteria of the genus Xanthomonas cause a variety of diseases in economically important monocotyledonous and dicotyledonous crop plants worldwide. Successful infection and bacterial multiplication in the host tissue often depend on the virulence factors secreted including adhesins, polysaccharides, LPS and degradative enzymes. One of the key pathogenicity factors is the type III secretion system, which injects effector proteins into the host cell cytosol to manipulate plant cellular processes such as basal defense to the benefit of the pathogen. The coordinated expression of bacterial virulence factors is orchestrated by quorum-sensing pathways, multiple two-component systems and transcriptional regulators such as Clp, Zur, FhrR, HrpX and HpaR. Furthermore, virule...
This paper reports regulation of hypoxia inducible factor-1 ? (HIF-1 ?)in hepatoma cells by irradiation. Cobalt chloride (CoCl2), a chemical mimic agent for hypoxia research, was utilized to induce the stable expression of HIF-1 ? in HepG2 cells. The HepG2 cells were irradiated to different doses to observe the changes of HIF-1 ?. The level of intracellular reactive oxygen species (ROS) was assayed by fluorescent microscope and flow cytometry (FCM). The results showed that there were obvious changes in expression of HIF-1 ? after HepG2 cells exposed to radiation, and the changes were positively related with the irradiation dose from 1 Gy to 5 Gy. Moreover, contents of incellular ROS were negatively correlated with above levels of HIF-1 ? from 1 Gy to 3 Gy. The results indicate that irradiation may enhance hypoxic cells HIF-1 ?, and the ...
Objective: Atherosclerosis is an inflammatory disease, modulated by plaque stabilizing and de-stabilizing cell populations such as infiltrating monocytes and vascular smooth muscle cells (vSMCs). Transcription factorsregulating proliferation and differentiation of atherosclerosis relevant cell types are of interest in this context. The forkhead box transcription factor FoxP1 modulates monocyte differentiation. We studied FoxP1 expression in atherosclerotic tissue, correlated FoxP1 expression with plaque characteristics and identified associations between FoxP1 and plaque proteins. Methods: 116 Atherosclerotic plaques from carotid endarterectomy samples were histologically classified (fibrous, fibroatheromatous, atheromatous) and subjected to semi-quantitative protein analysis. Macrophage,...
Mesenchymal stem cells (MSCs) are a potential source of smooth muscle cells (SMCs) for constructing tissue-engineered vascular grafts. However, the details of how specific combinations of vascular microenvironmental factorsregulate MSCs are not well understood. Previous studies have suggested that both mechanical stimulation with uniaxial cyclic strain and chemical stimulation with transforming growth factor {beta}1 (TGF-{beta}1) can induce smooth muscle markers in MSCs. In this study, we investigated the combined effects of uniaxial cyclic strain and TGF-{beta}1 stimulation on MSCs. By using a proteomic analysis, we found differential regulation of several proteins and genes, such as the up-regulation of TGF-{beta}1-induced protein ig-h3 (BGH3) protein levels by TGF-{beta}1 and up-regulation of calponin 3 protein level ...
Endoreduplication represents a cell cycle variant during which multiple rounds of DNA replication occur without subsequent chromosome separation and cytokinesis, resulting into a cellular increase of the DNA content. Although the DNA ploidy level of cells is controlled by external stimuli such as light, currently limited knowledge is available on how environmental signals regulate the endoreduplication cycle at the molecular level. Previously, we have demonstrated that the conversion from the mitotic cell cycle into an endoreduplication cycle is mediated by the atypical E2F transcription factor DEL1 that operates as a repressor of endocycle onset. Here, we identified DEL1 as a transcriptional target of the classical E2Fb and E2Fc transcription factors that antagonistically control DEL1 transcript levels through competition for a single E2F cis-acting binding ...
In a previous study, to identify genes of importance for hepatocellular carcinogenesis, and especially for processes involved in malignant transformation, the authors investigated differences in gene expression between adenomas and carcinomas by DNA microarray. In the present study, the authors investigated AW434047, one of the sequences that was upregulated in carcinomas. The investigation led to the identification of a novel gene, which the authors named hepatocyte malignant transforming factor (HMTF), of unknown function whose expression was increased in hepatocellular carcinomas. Northern blot and in situ hybridization also demonstrated high levels of HMTF in rat hepatocellular carcinoma (HCC) cell lines, lymphocytes in the spleen, colon mucosal epithelia, spermatocytes, and granule cells of the hippocampus. Reduction of HMTF by RNA interference (RNAi) in N1 cells, an HCC cell ...
Exogenous adenosine 5{prime}-triphosphate (ATP) mobilized intracellular calcium in human carcinoma A43l cells and in Swiss 3T3 and 3T6 mouse fibroblasts by increasing inositol trisphosphate similar to well down growth factors (platelet-derived growth factor (PDGF), epidermal growth factor (EGF), bradykinin (BK), serum). Calcium mobilization was examined by video imaging of fura-2 fluorescence is single cells, following the radioactive isotope {sup 45}Ca, and monitoring the decrease in fluorescence of cells loaded with chlortetracycline. Uridine 5{prime}-triphosphate, but not other nucleotides, mimicked ATP. Single-cell analysis revealed synchronous responses in 10 sec to ATP, BK or serum, while PDGF (3T3) and EGF (A431) produced slower signals with significant cell-to-cell variation. PDGF desensitized 3T3 ...
Neuropilin 1 (Nrp1) is a coreceptor for vascular endothelial growth factor A165 (VEGF-A165, VEGF-A164 in mice) and semaphorin 3A (SEMA3A). Nevertheless, Nrp1 null embryos display vascular...Full Text Available
BackgroundEstrogen receptors alpha (ERα) and beta (ERβ) are transcription factors (TFs) that mediate estrogen signaling and define the hormone-responsive phenotype...Full Text Available
Cyclin-Dependent Kinase 1 (CDK1) is the major M-phase kinase known also as the M-phase Promoting Factor or MPF. Studies performed during the last decade have shown many details of how CDK1 is regulated...Full Text Available
For proper tissue morphogenesis, cell divisions and cell fate decisions must be tightly and coordinately regulated. One elegant way to accomplish this is to couple them with asymmetric cell divisions....Full Text Available
As many as 59% of the transcription factors in Escherichia coli regulate the transcription rate of their own genes. This suggests that auto-regulation has one or more important...Full Text Available
MicroRNAs (miRs) can regulate many cellular functions, but their roles in regulating responses of vascular endothelial cells (ECs) to mechanical stimuli remain unexplored. We hypothesize that the physiological...Full Text Available
To study the regulation of adipose tissue lipoprotein lipase (LPL) in human adipocytes, omental adipose tissue was obtained from healthy subjects and digested in collagenase. The isolated adipocytes thus obtained were suspended in Medium 199 and cultured at 37 degrees C. Cell viability was demonstrated in adipocytes cultured for up to 72 h by constancy of cell number, cell size, trypan-blue exclusion, and specific /sup 125/I-insulin binding. In addition, chloroquine induced an increase in cell-associated /sup 125/I-insulin at 24, 48, and 72 h after preparation. Thus, isolated adipocytes retained their ability to bind, internalize, and degrade insulin. LPL was measured as activity secreted into the culture medium (CM), released from cells by heparin (HR), and extracted from cell digests. A broad range of heparin concentrations produced a ...
Neuron-restrictive silencer factor (NRSF) binds its consensus element to repress the transcription of various genes. The dominant-negative form (dnNRSF) has a hypertrophic effect on cardiogenesis through an unidentified mechanism. We examined the involvement of transient receptor potential (TRP) channel proteins, using transgenic mice overexpressing dnNRSF (dnNRSF mice). Electrophoretic mobility-shift assays revealed an interaction between NRSF and a neuron-restrictive silencer element-like sequence in intron 4 of TRPC1 genomic DNA. According to RT-PCR and Western analyses, TRPC1 was up-regulated in dnNRSF mouse heart. Transient overexpression of TRPC1 in HEK 293T cells increased the activity of the nuclear factor in activated T cells (NFAT) promoter and stimulated store-operated Ca"2"+ channel (SOCC)-mediated Ca"2"+ entry. Transfection of TRPC1 into primary cardiomyocytes increased ...
Besides differentiation and apoptosis, cell migration is a basic process in brain development in which neural cells migrate several centimeters within the developing brain before reaching their proper positions and forming the right connections. For identifying signaling events that control neural migration and are therefore potential targets of chemicals to disturb normal brain development, we developed a human neurosphere-based migration assay based on normal human neural progenitor (NHNP) cells, in which the distance is measured that cells wander over time. Applying this assay, we investigated the role of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the regulation of NHNP cell migration. Exposure to model substances like ethanol or phorbol 12-myristate 13-acetate (PMA) revealed a correlation between ERK1/2 activation and ...
Vascular endothelial growth factor (VEGF) is a mitogen that is critically involved in vasculogenesis, angiogenesis, and hematopoiesis. However, what and how transcription factors participate in the regulation of vegf gene expression are not fully understood. Here we report the cloning and sequencing of the zebrafish vegf promoter which revealed that the promoter contains a number of bone morphogenetic protein (BMP)-activated Smad binding elements (SBE), implicating Smad1 and Smad5 in the regulation of BMP-induced expression of vegf. Electrophoretic mobility shift assays of adding recombinant Smad proteins to the SBE-containing DNA oligonucleotides that represent portions of zebrafish vegf promoter resulted in mobility shift of the oligonucleotides. These changes demonstrate potential interactions between Smad1/5 and the vegf promoter. Reporter activity assays using the wild-type or SBE-deleted vegf ...
Elevated nuclear factor kappa B (NF-@kB) activity and interleukin-6 (IL-6) secretion participates in the pathology of several age and inflammatory-related diseases, including age-related macular degeneration (AMD), in which retinal pigment epithelial cells are the key target. Recent findings reveal that heat shock protein 70 (Hsp70) may affect regulation of NF-@kB. In the current study, effects of Hsp70 expression on NF-@kB RelA/p65 activity were evaluated in human retinal pigment epithelial cells (ARPE-19) by using celastrol, a novel anti-inflammatory compound. Anti-inflammatory properties of celastrol were determined by measuring expression levels of IL-6 and endogenous NF-@kB levels during lipopolysaccharide (LPS) exposure by using enzyme-linked immunosorbent assays (ELISA). Cell viabil...
Cytoreductive conditioning regimes designed to allow for successful allogeneic hematopoietic stem cell transplantation (allo-HSCT) paradoxically are also detrimental to recovery of the immune system in general but lymphopoiesis in particular. Post-transplant immune depletion is particularly striking within the T cell compartment which is exquisitely sensitive to negative regulation, evidenced by the profound decline in thymic function with age. As a consequence, regeneration of the immune system remains a significant unmet clinical need. Over the past decade studies have revealed several promising therapeutic strategies to address ineffective lymphopoiesis and post-transplant immune deficiency. These include the use of cytokines such as IL-7, IL-12 and IL-15; growth factors and hormones li...
The regulation of blood vessel formation is of fundamental importance to many physiological processes, and angiogenesis is a major area for novel therapeutic approaches to diseases from ischemia to...Full Text Available
Endogenous opioid peptides are substances involved in cell communication. They are present in various organs and tissues of the male and female reproductive tract, suggesting that they may regulate...Full Text Available
Because every cell within the body has the same genetic information, a significant problem in biology is to understand how cells within a tissue express genes selectively. A sophisticated network of physical and biochemical signals converge in a highly orchestrated manner to bring about the exquisite regulation that governs gene expression in diverse tissues. Thus, the ultimate decision of a cell to proliferate, express tissue-specific genes, or apoptose must be a coordinated response to its adhesive, growth factor, and hormonal milieu. The unifying hypothesis examined in this overview is that the unit of function in higher organisms is neither the genome nor the cell alone but the complex, three-dimensional tissue. This is because there are bidirectional connections between the components of the cellular microenvironment (growth factors, ...
The human olfactomedin 4 gene (OLFM4) encodes an olfactomedin-related glycoprotein. OLFM4 is normally expressed in a limited number of tissues, including the prostate, but its biological functions in prostate are largely unknown. In this study, we found that OLFM4 messenger RNA was reduced or undetectable in prostate cancer tissues and prostate cancer cell lines. To study the effects of OLFM4 on prostate cancer progression, we transfected PC-3 prostate cancer cells with OLFM4 to establish OLFM4-expressing PC-3 cell clones. The OLFM4-expressing PC-3 cell clones were found to have decreased proliferation and invasiveness compared with vector-transfected control PC-3 cells in vitro. In addition, nude mice injected with OLFM4-expressing PC-3 cells demonstrated reduced tumor growth and bone invasion and metastasis compared with mice injected with vector-transfected ...
BackgroundGene regulation is a key mechanism in higher eukaryotic cellular processes. One of the major challenges in gene regulation studies is to identify regulators affecting the...Full Text Available
BackgroundHuman Papillomavirus (HPV) E2 plays several important roles in the viral cycle, including the transcriptional regulation of the oncogenes E6 and E7, the regulation of the...Full Text Available
BackgroundThe mammalian FoxO transcription factors function to regulate diverse physiological processes. Emerging evidence that both BDNF and lithium suppress FoxO...Full Text Available
We report here a study of the mechanisms leading to loss of growth control in chicken embryo fibroblasts transformed by Rous sarcoma virus (RSV). We have been particularly concerned with the role of the src gene in this process, and have used RSV mutants temperature sensitive (ts) for transformation to investigate the nature of the growth regulatory lesion. The two principal findings were (1) the stationary phase of the cell cycle (G{sub 1}) in chick embryo fibroblasts seems to have two distinct regulatory compartments (using the terminology of Brooks et al. we refer to these as 'Q' and 'A' states). When rendered stationary at 41.5 C by serum deprivation, normal cells enter a Q state, but cells infected with the ts-mutant occupy an A state. (2) Whereas normal cells can occupy either state depending on culture conditions, the ts-infected cells, at ...
The Neurofibromatosis-2 (NF2) tumor suppressor merlin negatively regulatescell proliferation in numerous cell types. We have previously shown that the NF2...Full Text Available
Qualitative and quantitative aspects of the mechanisms involved in the regulation of cytoplasmic pH during an acid-load have been studied in Acer pseudoplatanus cells. Two main processes,...Full Text Available
In mice, coat pigmentation requires a stem cell (SC) system in which the survival, proliferation, and differentiation of melanocytes (MCs) are regulated by microenvironments in hair follicles (HFs). In vitro systems are required to analyze the behavior of single melanocyte stem cells (MCSCs) and their potential to form SC systems in vivo. We describe here an experimental system for the isolation, self-renewal, and differentiation of MCSCs, as well as an in vivo reconstitution assay for assessing their potential. Using Dct(tm1(Cre)Bee)/CAG-CAT-GFP mice, we show that, in the presence of stem cellfactor and basic fibroblast growth factor and the XB2 feeder cell line, purified MCSCs can undergo clonogenic proliferation, resulting in c-Kit(low) side scatter(low) cells. In culture, these cells maintain ...
Fibroblast growth factor (FGF) signaling has been shown to regulate lung epithelial development but its influence on mesenchymal differentiation has been poorly investigated. To study the role of mesenchymal FGF signaling in the differentiation of the mesenchyme and its impact on epithelial morphogenesis, we took advantage of Fgfr2c+/? mice, which due to a splicing switch express Fgfr2b in mesenchymal tissues and manifest Apert syndrome-like phenotypes. Using a set of in vivo and in vitro studies, we show that an autocrine FGF10?FGFR2b signaling loop is established in the mutant lung mesenchyme, which has several consequences. It prevents the entry of the smooth muscle progenitors into the smooth muscle cell (SMC) lineage and results in reduced fibronectin and elastin deposition. Levels of...
SummaryIn vivo tumor cell migration through integrin-dependent pathways is key to the metastatic behavior of malignant cells. Using quantitative in vivo...Full Text Available
Normal cells, both in vivo and in vitro, become quiescent after serial cell proliferation. During this process, cells can develop immortality with genomic instability,...Full Text Available
In preimplantation mouse development, the first cell lineages to be established are the trophectoderm (TE) and inner cell mass. TE possesses epithelial features, including apical-basal cell polarity...Full Text Available
Abstract Background/Aims: Transforming growth factor-b (TGF-b) initiates and maintains epithelial-mesenchymal transition (EMT), which causes disassembly of tight junctions and loss of epithelial cell polarity. In mature hepatocytes during EMT induced by TGF-b, changes in the expression of tight junction proteins and the fence function indicated that epithelial cell polarity remains unclear. Methods: In the present study, using primary cultures of adult rat hepatocytes at day 10 after plating, in which epithelial cell polarity is well maintained by tight junctions, we examined the effects of 0.01-20 ng/ml TGF-b on the expression of the integral tight junction proteins, claudin-1, -2 and occludin, as well as the fence function. Results: In adult rat hepatocytes, TGF-b induced EMT, which was ...
ABSTRACT-Here we identify release of annexin A2 into the culture medium in response to low dose X-ray radiation exposure and establish functional linkages to an established paracrine factor-mediated anchorage-independent growth response. Using a standard bicameral coculture model, we observe that annexin A2 levels associated with non-irradiated neighboring cells seeded in the lower chamber (annexin A2 silenced [shRNA] JB6 cells) are increased upon coculture with irradiated (10-50 cGy) JB6 cells seeded in the upper chamber, relative to coculture with sham exposed JB6 cells seeded in the upper chamber, suggesting that annexin A2 released into the medium is capable of communicating in a paracrine fashion. Using a previously established coculture model, we observed that the paracrine factor-mediated anchorage-independent growth response to low dose X-ray radiation ...
Reproductive status influences cell proliferation and the survival of new cells in the dentate gyrus of adult laboratory-reared and wild female meadow voles; reproductively inactive (RI) females have more proliferating cells and more labeled cells that survive 5 weeks vs. 2 h than reproductively active (RA) females. However, the effect of season has only been studied in a wild sample of male meadow voles and factors such as age and experience that have been shown to influence neurogenesis in the dentate gyrus of adult mammals cannot be controlled in a wild sample. Therefore, we investigated whether reproductive status regulates neurogenesis (cell proliferation and/or the survival of new cells) in the dentate gyrus of laboratory-reared adult male meadow voles so that confounding variables could be controlled. Males were ...
A crucial step in human breast cancer progression is the acquisition of invasiveness. There is a distinct lack of human cell culture models to study the transition from pre-invasive to invasive phenotype as it may occur 'spontaneously' in vivo. To delineate molecular alterations important for this transition, we isolated human breast epithelial cell lines that showed partial loss of tissue polarity in three-dimensional reconstituted-basement membrane cultures. These cells remained non-invasive; however, unlike their non-malignant counterparts, they exhibited a high propensity to acquire invasiveness through basement membrane in culture. The genomic aberrations and gene expression profiles of the cells in this model showed a high degree of similarity to primary breast tumor profiles. The xenograft tumors formed by the cell lines in three different microenvironments ...
Background & AimsMolecular mechanisms underlying alcoholic liver disease (ALD) are still not fully understood. Activating transcription factor-4 (ATF4) is the master coordinator of the integrated stress response (ISR), an adaptive pathway triggered by multiple stressors. which can promote cell death and induce metabolic dysregulation if the stress is intense or prolonged. The aim of this study was to assess the effect of alcohol on the ISR signaling pathway in human liver cells and to define the role of cytochrome P450 2E1 (CYP2E1) in this response. MethodsPrimary cultured human hepatocytes and human HepG2 cells over-expressing CYP2E1 by adenoviral infection were exposed to ethanol (25-100mM) for 8-48h. ResultsEthanol treatment of both liver cells up-regulated ATF4 as well as the pro-survi...
The ternary complex factor (TCF) Elk-1 is a transcription factor that regulates immediate early gene (IEG) expression via the serum response element (SRE) DNA consensus site. Elk-1 is associated with...Full Text Available
SUMMARYThe cytolytic activity of natural killer (NK) cells is regulated by inhibitory receptors that detect the absence of self molecules on target cells. Structural studies of...Full Text Available
The proliferation of stem cell research, conflated with its ethical and moral implications, has led governments to attempt regulation of both the science and funding of stem cells. Due to a diversity...Full Text Available
Background: Protein disulfide isomerase (PDI) controls platelet integrin function, tissue-factor (TF) activation, and concentrates at fibrin and thrombus formation sites of vascular injury. Objective: We investigated involvement of surface thiol isomerases and especially PDI, in thrombin-mediated thrombin amplification on human platelets. Methods/Results: Using a new developed thrombin-dependent platelet thrombin generation assay we observed that the feedback activation of thrombin generation on the platelet surface does not depend on TF, as anti-TF antibodies inhibiting TF-induced thrombin formation in platelet-depleted plasma had no effect compared to vehicle-treated controls. Feedback activation of thrombin generation in the presence of platelets was significantly diminished by membrane impermeant thiol blockers or by the thiol isomerase-inhibitors bacitracin and anti-PDI antibody RL90, respectively. Platelet thrombin formation depends on binding of coagulation ...
Fish retinal ganglion cells (RGCs) can survive and regrow their axons after optic nerve injury. Injured RGCs express anti-apoptotic proteins, such as Bcl-2, after nerve injury; however, upstream effectors of this anti-apoptotic protein are not yet fully understood. Heat shock proteins (HSPs) play a crucial role in cell survival against various stress conditions. In this study, we focused on HSP70 expression in the zebrafish retina after optic nerve injury. HSP70 mRNA and protein levels increased rapidly 2.3-fold in RGCs by 1-6 h after injury and returned to control levels by 1-3 days. HSP70 transcription is regulated by heat shock factor 1 (HSF1). HSF1 mRNA and phosphorylated-HSF1 protein rapidly increased by 2.2-fold in RGCs 0.5-6 h after injury. Intraocular injection of HSP inhibitor I s...
Although acetylated α-tubulin is known to be a marker of stable microtubules in neurons, precise factors that regulate α-tubulin acetylation are, to date, largely unknown. Therefore,...Full Text Available
Growth hormone (GH) has an important role in the regulation of hepatic LDL receptor expression and plasma lipoprotein levels. This investigation was undertaken to evaluate if these effects of GH on...Full Text Available
BackgroundThe MYC transcription factors are known to be involved in the biology of many human cancer types. But little is known about the Myc/microRNAs cooperation in the regulation...Full Text Available
The target of rapamycin (TOR) pathway regulatescell growth and aging in various organisms. In Saccharomyces cerevisiae, silent information regulator 2 (Sir2) modulates cellular senescence. Moreover,...Full Text Available
SummaryThe Hippo tumor-suppressor pathway controls tissue growth in Drosophila and mammals by regulatingcell proliferation and apoptosis. The Hippo pathway includes...Full Text Available
Menin, which is encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, is a tumor suppressor and transcriptional regulator. Menin controls proliferation and apoptosis of cells, especially pancreatic...Full Text Available
The majority of diseases in the retina are caused by genetic mutations affecting the development and function of photoreceptor cells. The transcriptional networks directing these processes are regulated...Full Text Available
Cytokinins are hormones that regulatecell division and development. As a result of a lack of specific mutants and biochemical tools, it has not been possible to study the consequences of cytokinin...Full Text Available
SUMMARYATG12, an ubiquitin-like modifier required for macroautophagy, has a single known conjugation target, another autophagy regulator called ATG5. Here, we identify ATG3 as...Full Text Available
Immune function is critical in health and disease. The control and regulation of immune reactions is an area of intense investigation that has important implications for allogeneic hematopoietic cell transplantation. Immune reactions are regulated in a number of important ways. Compartmentalization of immune responses and the production of both pro-inflammatory and anti-inflammatory cytokines play a major role. More recently several populations of T cells that regulate immune responses termed regulatory T cells have been identified. This manuscript will focus on CD4^+CD25^+FoxP3^+ natural regulatory T cells (T"r"e"g) and @a@bTCR^+CD4^+NK1.1^+ natural killer T (NK-T) cells which both suppress graft vs host disease but appear to function by distinct mechanisms.
Senescence is regarded as a physiological response of cells to stress, including telomere dysfunction, aberrant oncogenic activation, DNA damage, and oxidative stress. This stress response has an antagonistically...Full Text Available
Within the cardiac cell, the movements of calcium ions are tightly regulated by a number of regulatory proteins including pumps, and channels. The sarcoplasmic reticulum (SR) is in large part...Full Text Available
Contractile vacuole complexes are critical components of cell volume regulation and have been shown to have other functional roles in several free-living protists....Full Text Available
The role of apoptosis or programmed cell death in the regulation of development and maintenance of homeostasis in multicellular organisms is well established. During the last decade, naturally...Full Text Available
Totipotent stem cells have the potential to differentiate into every cell type. Renewal of totipotent stem cells in the germline and cellular differentiation during early embryogenesis rely upon posttranscriptional...Full Text Available
Interleukin 2 (IL-2) and B-cell growth factors I and II (BCGF I and BCGF II) are lymphokines produced by T cells that play a major role in T- and B-cell cooperation. Peripheral blood lymphocytes from...Full Text Available
BackgroundStem cell characteristics are an important feature of human cancer cells and play a major role in the therapy resistance of tumours. Strategies to target cancer stem cells...Full Text Available
Hepatic injury and regeneration of the liver are associated with activation of hepatic stellate cells (HSC). Fibroblast growth factors (FGFs) and their receptors are important regulators of repair in various tissues. HSC express FGFR3IIIc as well as FGFGR4 and different spliced FGFR1IIIc and FGFR2IIIc isoforms which differ in the presence or absence of the acid box and of the first Ig-like domain. Expression of FGF9, known to be capable to activate the HSC FGFR2/3-isoforms, was increased in HSC in liver slice cultures after exposition to carbon tetrachloride, as an acute liver injury model. FGF9 significantly stimulated 3-H thymidine incorporation of hepatocytes, but failed to induce DNA synthesis in HSC despite the fact that FGF9 induced a sustained activation of extracellular signal-related kinases (ERK) 1/2. FGF9 induced an increased phosphorylation of Tyr436 of the fibroblast growth factor receptor ...
Basic fibroblast growth factor (bFGF) exhibits specific binding to the extracellular matrix (ECM) produced by cultured endothelial cells. Binding was saturable as a function both of time and of concentration of {sup 125}I-bFGF. Scatchard analysis of FGF binding revealed the presence of about 1.5 x 10{sup 12} binding sites/mm{sup 2} ECM with an apparent k{sub D} of 610 nM. FGF binds to heparan sulfate (HS) in ECM as evidenced by (i) inhibition of binding in the presence of heparin or HS at 0.1-1 {mu}g/mL, but not by chondroitin sulfate, keratan sulfate, or hyaluronic acid at 10 {mu}g/mL, (ii) lack of binding to ECM pretreated with heparitinase, but not with chondroitinase ABC, and (iii) rapid release of up to 90% of ECM-bound FGF by exposure to heparin, HS, or heparitinase, but not to chondroitin sulfate, keratan sulfate, hyaluronic acid, or chondroitinase ABC. Oligosaccharides derived from depolymerized heparin, and as small as the ...
The Drosophila melanogaster tissue-specific transcription factor NTF-1 was originally identified in vitro as a protein that could bind to and activate transcription from the Dopa decarboxylase (Ddc) gene. A structure-function analysis of NTF-1 led to the identification of a discrete amino-terminal activation domain. Here, we report that an NTF-1 mutant lacking the activation domain acts as a trans-dominant inhibitor of NTF-1 activation in tissue culture cells by forming inactive heterodimers with the full-length protein. Ectopically expressing this dominant-negative protein or the full-length protein in developing Drosophila embryos leads to dire developmental consequences. Overexpressing the trans-dominant NTF-1 leads to lethality, while overexpressing full-length NTF-1 results in both lethality and morphogenetic defects. Our results suggest that both the activity and the regulation of NTF-1 are critical for viability and ...
Opinions on factors affecting public power systems are presented. Social, economic, and political factors are discussed in terms of their impact on public power. Competition with investor-owned utilities is the primary focus of the paper. Privatization and regulations are other issues discussed.
Many growth factors and hormones modulate the reproductive status in mammals. Among these, insulin and insulin-like growth factor I (IGF-I) regulate the development of gonadal tissues. SH2-B has been...Full Text Available
Cellular hypertrophy is regulated by coordinated pro- and antigrowth machineries. Foxo transcription factors initiate an atrophy-related gene program to counter hypertrophic growth. This study was designed...Full Text Available
The ETS proteins are a family of transcription factors (TFs) that regulate a variety of biological processes. We made genome-wide analyses to explore the classification of the ETS gene family. We identified...Full Text Available
BackgroundThe dynorphin-kappa opioid receptor (KOR) system regulates glial proliferation after sciatic nerve injury. Here, we investigated its role in cell proliferation following...Full Text Available
Syndecan-2, a transmembrane heparan sulfate proteoglycan, is a critical mediator in the tumorigenesis of colon carcinoma cells. We explored the function of syndecan-2 in melanoma, one of the most invasive...Full Text Available
During embryonic development, cells are instructed which position to occupy, they interpret these cues as differentiation programmes, and expand these patterns by growth. Sonic hedgehog...Full Text Available
Taste cells use multiple signaling mechanisms to generate appropriate cellular responses to discrete taste stimuli. Some taste stimuli activate G protein coupled receptors (GPCRs) that cause calcium...Full Text Available
BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most aggressive carcinomas of the gastrointestinal tract. We assessed the relevance of Slug in measuring the invasive...Full Text Available
BackgroundGlycochenodeoxycholate (GCDA) is one of the major human bile salts. Bile salts stimulate cell survival and proliferation through the mitogen-activated protein kinase, but...Full Text Available
Measurements were made of 45Ca influx into isolated internodal cells of Chara corallina and also into internodal cells of intact plants. 45Ca influx was closely...Full Text Available
Stem cells are expected to play a key role in the development and maintenance of organisms, and hold great therapeutic promises. However, a number of questions must be answered to achieve an...Full Text Available
The ubiquitin–proteasome pathway is the principal system for extralysosomal protein degradation in eukaryotic cells, and is essential for the regulation and maintenance of basic cellular processes,...Full Text Available
Cancer cells constantly adapt to oxidative phosphorylation (OXPHOS) suppression resulting from hypoxia or mitochondria defects. Under the OXPHOS suppression, AMP-activated protein kinase (AMPK) regulates...Full Text Available
BackgroundNKX2-3 is associated with inflammatory bowel disease (IBD). NKX2-3 is expressed in microvascular endothelial cells and the muscularis...Full Text Available
PurposeThe size of neuronal populations is modulated by gene variants that influence cell production and survival, in turn influencing neuronal connectivity, function,...Full Text Available
BackgroundThe zebrafish is recognized as a versatile cancer and drug screening model. However, it is not known whether the estrogen-responsive genes and signaling pathways that are...Full Text Available
Type 2 diabetes mellitus (T2DM) results from insulin resistance and β-cell dysfunction, in the setting of hyperglucagonemia. Glucagon is a 29 amino acid peptide hormone, which is secreted from...Full Text Available
SummaryDnaA initiates chromosomal replication in E. coli at a well regulated time in the cell-cycle. To determine how the spatial distribution of DnaA is related...Full Text Available
The immunogenicity of allogeneic cultured human epidermal keratinocytes (cHEKs) has been studied in several models with contradictory results. We studied human T-cell activation in an in vitro...Full Text Available
Mitogen Activated Protein Kinases (MAPKs) are a class of serine/threonine kinases that regulate a number of different cellular activities including cell proliferation, differentiation, survival and...Full Text Available
To study the effect of agonist on the TRH (thyrotrophin-releasing hormone) receptor protein, an epitope-tagged receptor was stably expressed in HEK-293 cells (human embryonic kidney 293 cells) and receptor...Full Text Available
Mechanical forces can regulate various functions in living cells. The cytoskeleton is a crucial element for the transduction of forces in cell-internal signals and subsequent biological responses. Accordingly,...Full Text Available
Epigenetic regulations of genes by reversible methylation of DNA (at the carbon-5 of cytosine) and numerous reversible modifications of histones play important roles in normal physiology and development, and epigenetic deregulations are associated with developmental disorders and various disease states, including cancer. Stem cells have the capacity to self-renew indefinitely. Similar to stem cells, some malignant cells have the capacity to divide indefinitely and are referred to as cancer stem cells. In recent times, direct correlation between epigenetic modifications and reprogramming of stem cell and cancer stem cell is emerging. Major discoveries were made with investigations on reprogramming gene products, also known as master regulators of totipotency and inducer of pluoripotency, na...
α1-Fetoprotein transcription factor (FTF), also known as liver receptor homolog 1 (LRH-1) is highly expressed in liver and intestine, where it is implicated in the regulation...Full Text Available
HCV-Ag-specific TH17 cells secrete IL17, a cytokine involved in autoimmune diseases and regulated by IL10 and TGF-b. 5–12% of patients with chronic HCV infection have hypothyroidism. We evaluated...Full Text Available
Innate immune responses are regulated by microorganisms and cell death, as well as by a third class of stress signal from the nervous and endocrine systems. The innate immune system also feeds back, through the production of cytokines, to regulate the function of the central nervous system (CNS), and this has effects on behaviour. These signals provide an extrinsic regulatory circuit that links physiological, social and environmental conditions, as perceived by the CNS, with transcriptional 'decision-making' in leukocytes. CNS-mediated regulation of innate immune responses optimizes total organism fitness and provides new opportunities for therapeutic control of chronic infectious, inflammatory and neuropsychiatric diseases.
Vascular permeability factor (VPF) is an Mr 40-kD protein that has been purified from the conditioned medium of guinea pig line 10 tumor cells grown in vitro, and increases fluid permeability from blood...Full Text Available
BackgroundPerichondrium is recognized as a tissue with chondrogenic potential yielding cells which can be used for osteochondral repair. Factors which influence the proliferative...Full Text Available
Various factors affecting the aggregation of Actinomyces naeslundii strain 12104 were studied. When the pH of glucose-supplemented growth medium fell below 5.5, the cells aggregated and formed microbial...Full Text Available
Hyperosmotic stress is known to significantly enhance net uptake of inorganic ions into plant cells. Direct evidence for cell turgor recovery via such a mechanism, however, is still lacking. In the...Full Text Available
Eukaryotic genomes encode a zinc finger protein (ZPR1) with tandem ZPR1 domains. In response to growth stimuli, ZPR1 assembles into complexes with eukaryotic translation elongation factor 1A (eEF1A) and the survival motor neurons protein. To gain insight into the structural mechanisms underlying the essential function of ZPR1 in diverse organisms, we determined the crystal structure of a ZPR1 domain tandem and characterized the interaction with eEF1A. The ZPR1 domain consists of an elongation initiation factor 2-like zinc finger and a double-stranded {beta} helix with a helical hairpin insertion. ZPR1 binds preferentially to GDP-bound eEF1A but does not directly influence the kinetics of nucleotide exchange or GTP hydrolysis. However, ZPR1 efficiently displaces the exchange factor eEF1B from preformed nucleotide-free complexes, suggesting that it may function as a negative regulator of eEF1A activation. ...
There is ample evidence suggesting that superantigens may act as a triggering factor in the pathogenesis of rheumatoid arthritis (RA). We investigated whether superantigen could activate T cells in...Full Text Available
Myostatin is a member of the transforming growth factor-{beta} (TGF-{beta}) family and a strong negative regulator of muscle growth. Here, we present the crystal structure of myostatin in complex with the antagonist follistatin 288 (Fst288). We find that the prehelix region of myostatin very closely resembles that of TGF-{beta} class members and that this region alone can be swapped into activin A to confer signalling through the non-canonical type I receptor Alk5. Furthermore, the N-terminal domain of Fst288 undergoes conformational rearrangements to bind myostatin and likely acts as a site of specificity for the antagonist. In addition, a unique continuous electropositive surface is created when myostatin binds Fst288, which significantly increases the affinity for heparin. This translates into stronger interactions with the cell surface and enhanced myostatin degradation in the presence of either Fst288 or Fst315. ...
NFAT involvement in adipocyte physiological processes was examined by treatment with CsA and/or GSK3{beta} inhibitors (Li{sup +} or TZDZ-8), which prevent or increase NFAT nuclear translocation, respectively. CsA treatment reduced basal and TNF{alpha}-induced rates of lipolysis by 50%. Adipocytes preincubated with Li{sup +} or TZDZ-8 prior to CsA and/or TNF{alpha}, exhibited enhanced basal rates of lipolysis and complete inhibition of CsA-mediated decreased rates of lipolysis. CsA treatment dramatically reduced the mRNA levels of adipocyte-specific genes (aP2, HSL, PPAR{gamma}, ACS and Adn), compared with control or TNF{alpha}-treatment, whereas Li{sup +} pretreatment blocked the inhibitory effects of CsA, and mRNA levels of aP2, HSL, PPAR{gamma}, and ACS were found at or above control levels. NFAT nuclear localization, assessed by EMSA, confirmed that CsA or Li{sup +} treatments inhibited or increased NFAT nuclear translocation, respectively. These results show that NFAT proteins in ...
The role of intracellular Ca2+ (Ca2+i) on hematopoiesis was investigated in long term bone marrow cultures using cytokines and agonists of P2 receptors. Cytokines interleukin 3 and granulocyte/macrophage colony stimulator factor promoted a modest increase in Ca2+i concentration ([Ca2+]i) with activation of phospholipase Cgamma, MEK1/2, and Ca2+/calmodulin kinase II. Involvement of protein kinase C was restricted to stimulation with interleukin 3. In addition, these cytokines promoted proliferation (20 times) and an increase in the Gr-1(-)Mac-1+ population with participation of gap junctions (GJ). Nevertheless ATP, ADP, and UTP promoted a large increase in [Ca2+]i, moderate proliferation (6 times), a reduction in the primitive Gr-1(-)Mac-1(-)c-Kit+ population, and differentiation into macrophages without participation of GJ. It is likely that Ca2+i participates as a regulator of hematopoietic signaling: moderate increases in [Ca2+]i would be ...
We investigated possible mechanism(s) where honokiol induces apoptosis in human hepatocellular carcinoma SMMC-7721 cells. MTT assay showed that honokiol has strong inhibition on SMMC-7721 cells in a dose-dependent manner. SMMC-7721 cells after honokiol treatment display morphological characteristics such as cell shrinkage, detachment from the culture plate, formation of apoptotic bodies, change to a round shape, and marked nuclear condensation and fragmentation after 32258 staining. Cell apoptosis was measured by Annexin-V/PI staining and alternatively, by the subG0/G1 percentage of the cell cycle analysis followed by FACS. An obvious loss of ??(m) and a quick burst of ROS was detected when honokiol reached 4?g/ml, which was coincident with the high apoptosis percentage in our previous research. Up-regulation of Bax and ...
BackgroundThe Mre11/Rad50/Nbs1 (MRN) complex is a regulator of cell cycle checkpoints and DNA repair. Defects in MRN can lead to defective S-phase arrest when cells are damaged....Full Text Available
Heterochromatin constitutes a significant portion of the genome in higher eukaryotes; approximately 30% in Drosophila and human. Heterochromatin contains a high repeat DNA content and a low density of protein-encoding genes. In contrast, euchromatin is composed mostly of unique sequences and contains the majority of single-copy genes. Genetic and cytological studies demonstrated that heterochromatin exhibits regulatory roles in chromosome organization, centromere function and telomere protection. As an epigenetically regulated structure, heterochromatin formation is not defined by any DNA sequence consensus. Heterochromatin is characterized by its association with nucleosomes containing methylated-lysine 9 of histone H3 (H3K9me), heterochromatin protein 1 (HP1) that binds H3K9me, and Su(var)3-9, which methylates H3K9 and binds HP1. Heterochromatin formation and functions are influenced by HP1, Su(var)3-9, and the RNA interference (RNAi) pathway. My thesis project ...
Effects of cell concentrations on the survival and repopulation of haemopoietic stem cells after irradiation were studied in the long-term culture of mouse bone marrow cells in vitro. No difference was observed in the survival of the stem cells among cultures in which 0 - 10/sup 7/ cells were re-inoculated on the adherent cell colonies in the culture flask. Stem cells showed a significant proliferation within 1 week and the number of the stem cells exceeded the control in 3 weeks after irradiation in the cultures with less than 10/sup 6/ re-inoculated cells per flask. In contrast, there was a considerable delay in the onset of stem cell proliferation after irradiation in the culture with 10/sup 7/ cells per flask. Based on these results, a possibility that a ...
The IRG protein Irgm3 preserves cell survival during coxsackievirus B3 (CVB3) infection. However, the molecular mechanisms are not clear. Here, we examined the effect of Irgm3 expression on ER stress triggered by pharmacological agents or CVB3 infection. In Tet-On/Irgm3 HeLa cells, Irgm3 expression suppressed either chemical- or CVB3-induced upregulation of glucose-regulated protein78. Further, Irgm3 strongly inhibited the activation of both the PERK and ATF6 pathways of ER stress responses, which further led to the diminished phosphorylation of eIF2?, reduced cleavage/activation of transcription factor SREBP1 and attenuated induction of proapoptotic genes CHOP and GADD34. These data were further supported by experiments using Irgm3 knockout mouse embryonic fibroblasts, in which the ER stress induced by CVB3 was not relieved due to the lack of Irgm3 expression. In addition, the tunicamycin-triggered ER ...
Purpose of ReviewThe vertebrate cap’n’collar family transcription factor Nrf2 and its invertebrate homologs SKN-1 (in worms) and CncC (in flies) function...Full Text Available
CBP and its paralog p300 are histone acetyl transferases that regulate gene expression by interacting with multiple transcription factors via specialized domains. The structure...Full Text Available
The processes regulating telomere function have major impacts on fundamental issues in human cancer biology. First, active telomere maintenance is almost always required for full oncogenic transformation...Full Text Available
Adipocyte differentiation is a complex developmental process that involves the coordinated interplay of numerous transcription factors. PPARγ has emerged as a master regulator of adipogenesis...Full Text Available
A mild reduction in mitochondrial respiration extends the life span of many species, including C. elegans. We recently showed that hypoxia-inducible factor 1 (HIF-1) is required for...Full Text Available
Dissecting the genes involved in complex traits can be confounded by multiple factors, including extensive epistatic interactions among genes, the involvement of epigenetic regulators, and the variable...Full Text Available
Edema factor (EF) and CyaA are calmodulin (CaM)-activated adenylyl cyclase exotoxins involved in the pathogenesis of anthrax and whooping cough, respectively. Using spectroscopic, enzyme kinetic and...Full Text Available
Skeletal formation is an essential and intricately regulated part of vertebrate development. Humans and mice deficient in Growth and Differentiation Factor 6 (Gdf6) have numerous...Full Text Available
BACKGROUND: Mitochondrial changes have been described in muscle tissue in acquired hypothyroidism. Among the molecular mechanisms by which thyroid hormones regulate expression of nuclear genes encoding...Full Text Available
The sirtuin Sirt6 is a NAD-dependent histone deacetylase that is implicated in gene regulation and lifespan control. Sirt6 can interact with the stress-responsive transcription factor NF-κB...Full Text Available
BackgroundThe transcription factor Pax6 is essential for the development of the central nervous system and it exerts its multiple functions by regulating the expression of downstream...Full Text Available
Circadian clock is implicated in the regulation of aging. The transcription factor CLOCK, a core component of the circadian system, operates in complex with another circadian clock protein BMAL1. Recently...Full Text Available
Mechanisms regulating sexual differentiation of the zebra finch song system appear to include both genetic and hormonal factors. Sorting Nexin 2 (SNX2), which is involved in trafficking proteins...Full Text Available
Cellular cholesterol homeostasis is controlled by sterol-regulated proteolysis of membrane-bound transcription factors called sterol-regulatory element binding proteins (SREBPs). CPP32, a cysteine protease,...Full Text Available
Psychopathic individuals are generally unresponsive to motivational and emotional cues that facilitate behavioral regulation. A putative mechanism for this deficiency is Gray’s (1971)...Full Text Available
Recent evidence suggests a role for corticotropin-releasing factor (CRF) in the regulation of pair bonding in prairie voles. We have previously shown that monogamous and non-monogamous vole...Full Text Available
The tumor suppressor adenomatous polyposis coli (APC) is mutated in the majority of colorectal cancers and is best known for its role as a scaffold in a Wnt-regulated protein complex that determines...Full Text Available
SummaryActivating transcription factor 2 (ATF2) is regulated by JNK/p38 in response to stress. Here, we demonstrate that the protein kinase ATM phosphorylates ATF2 on serines...Full Text Available
BackgroundObesity is one of the principal causative factors involved in the development of metabolic syndrome. AMP-activated protein kinase (AMPK) is an energy sensor that regulates...Full Text Available
The resulting emissions of the firing of ceramic products of all type are described, the factors are enumerated to diminish the emissions in the kilns and the technologies applied in the kilns to reduce these emissions while carrying out energy saving are described briefly. (author)
A conserved multi-subunit complex (MybMuvB, MMB), regulates transcriptional activity of many different target genes in Drosophila somatic cells. A paralogous complex, tMAC, controls...Full Text Available
The long pentraxin PTX3 has multiple roles in innate immunity. For example, PTX3 regulates C1q binding to pathogens and dead cells and regulates their uptake by phagocytes. It also inhibits P-selectin-mediated...Full Text Available
The phosphatidylinositol pathway is implicated in the regulation of numerous cellular functions and responses to extracellular signals. An important branching point in the pathway is the phosphorylation...Full Text Available
Forward and reverse genetic experiments have both played important roles in revealing critical aspects of mammalian signal transduction pathways in cell culture experiments. Only recently have we begun...Full Text Available
Uracil appears in DNA as a result of cytosine deamination and by incorporation from the dUTP pool. As potentially mutagenic and deleterious for cellregulation, uracil must be removed from DNA....Full Text Available
Cytosine methylation in DNA is a major epigenetic signal, and plays a central role in propagating chromatin status during cell division. However the mechanistic links between DNA methylation...Full Text Available
The lesion bypass pathway, which is regulated by monoubiquitination of proliferating cell nuclear antigen (PCNA), is essential for resolving replication stalling due to DNA lesions. This process is...Full Text Available
The gram-positive pathogen Streptococcus pyogenes was recently reported to possess a homologue of the luxS gene that is responsible for the production of autoinducer...Full Text Available
During reproduction in flowering plants, pollen grains form a tube that grows in a polarized fashion through the female tissues to eventually fertilize the egg cell. These highly polarized pollen tubes...Full Text Available
The canonical Wnt/β-catenin pathway plays a pivotal role in regulating embryogenesis and tumorigenesis by promoting cell proliferation. BAMBI (BMP and activin membrane-bound inhibitor) has...Full Text Available
PurposeIn our previous studies we showed that upregulating claudin-6 (CLDN6) expression may contribute to preventing breast cancer, and that 17β-estradiol induces a concentration-...Full Text Available
The secreted Bv8 protein has been recently characterized as a regulator of myeloid cell mobilization and a neutrophil-derived mediator of tumor angiogenesis in several xenografts, but its role in tumor...Full Text Available
Rapamycin inhibits the mTOR (target of rapamycin) pathway and extends lifespan in multiple species. The tuberous sclerosis complex (TSC) protein is a negative regulator of mTOR. In humans, loss of the...Full Text Available
Mycolic acids are key cell wall components for the survival, pathogenicity, and antibiotic resistance of the human tubercle bacillus. Although it was thought that Mycobacterium tuberculosis...Full Text Available
Chemical reactions in living cells are under strict enzyme control and conform to a tightly regulated metabolic program. However, uncontrolled and potentially deleterious endogenous reactions occur,...Full Text Available
Hematopoietic stem and progenitor cell (HSPC) expansion is regulated by intrinsic signaling pathways activated by cytokines. The intracellular kinase JAK2 plays an essential role in cytokine signaling,...Full Text Available
Cdc13 is a single stranded telomere binding protein that specifically localizes to the telomere ends of budding yeasts and is essential for cell viability. It caps the ends of chromosomes thus preventing...Full Text Available
Acetaminophen (APAP), a widely used analgesic and antipyretic that is considered to be relatively safe at recommended doses, is the leading cause of drug-induced liver failure in the United States....Full Text Available
Reversible protein glutathionylation plays a key role in cellular regulation and cell signaling and protects protein thiols from hyperoxidation. Sulfiredoxin (Srx), an enzyme that catalyzes the reduction...Full Text Available
The role of cytochrome c (Cyt c) in caspase activation has largely been established from mammalian cell-culture studies, but much remains to be learned about its physiological...Full Text Available
Proteins that metabolize or bind the nucleotide second messenger cyclic diguanylate regulate a wide variety of important processes in bacteria. These processes include motility, biofilm formation, cell...Full Text Available
Metazoan development requires complex mechanisms to generate cells with diverse function. Alternative splicing of pre-mRNA not only expands proteomic diversity but also provides a means to regulate...Full Text Available
SummarySpatial control of gene expression, at the level of both transcription and translation, is critical for cellular differentiation [1-Full Text Available
In most insect species, juvenile hormones regulate critical physiological processes such as metamorphosis and reproduction. In insects, these sesquiterpenoids are synthesized by retrocerebral endocrine...Full Text Available
Atg9 is a transmembrane protein essential for autophagy which cycles between the Golgi network, late endosomes and LC3-positive autophagosomes in mammalian cells during starvation through a mechanism...Full Text Available
Arabidopsis thaliana SUPERMAN (SUP) plays an important role during flower development by maintaining the boundary between stamens and carpels in the inner two whorls....Full Text Available
Amyloid precursor protein (APP), implicated in Alzheimer's disease, is a transmembrane protein of undetermined function. APP is cleaved by gamma-secretase that releases the APP intracellular domain...Full Text Available
From Toki-shakuyaku-san, an herbal formulation for “cleansing stagnated blood,” a key gene regulatory compound was purified and identified through a screening based on DNA microarray...Full Text Available
Assessment of the regulation of plant metabolism by the calcium ion requires a knowledge of its intracellular levels and dynamics. Technical problems have prevented direct measurement of the concentration...Full Text Available
Phospholipase D (PLD) has been recognized as a regulator of cell proliferation and tumorigenesis, but little is known about the molecules regulating PLD expression. Thus, the identification of small molecules inhibiting PLD expression would be an important advance in PLD-mediated physiology. Quercetin, a ubiquitous bioactive flavonoid, is known to inhibit proliferation and induce apoptosis in a variety of cancer cells. In the present study, we examined the effect of quercetin on the expression of PLD in U87 glioma cells. Quercetin significantly suppressed the expression of PLD1 at the transcriptional level. Moreover, quercetin abolished the protein expression of PLD1 in a time and dose-dependent manner, as well as inhibited PLD activity. Quercetin suppressed NFkB-induced PLD1 expression vi...
Increasing evidence has been accumulated indicating the important role of epigenetic regulation in tumor genesis. Previously, we observed that the transfection of hepatitis C virus core (HCVc) protein led to malignant transformation in normal biliary cells, and that tumor suppressor gene RASSF1A was downregulated in many hilar cholangiocarcinoma patients by hypermethylation in the promoter region. In the present study, we found SET and MYND domain-containing protein 3 (SMYD3), a novel histone methyltransferase, was overexpressed in cholangiocarcinoma patients especially in those with HCV infection. Transfection of HCVc into hilar cholangiocarcinoma cell lines QBC939 and FRH0201 could upregulate the expression of SMYD3 and promote cell growth, which was consistent with the results of our cl...
BACKGROUND Hypermethylation of CpG islands is a common epigenetic alteration associated with cancer. Tumor suppressor genes retinoic acid receptor beta (RARb) and PDLIM4 are hypermethylated and silenced in prostate cancer (PCa) tissues and PCa cell lines compared to normal prostate cells. METHODS In this study, a benign prostate epithelial cell line RWPE1 was used as a model to study the epigenetic regulation of Myc on the RARb and PDLIM4 promoters. Forced Myc overexpression inhibited the RARb and PDLIM4 expression. RESULTS Pyrosequencing study showed that Myc overexpression increased methylation in several CpG sites of both promoters. A DNA methylation inhibitor 5-aza-2prime-deoxycytidine reversed the epigenetic alteration effect of Myc on both RARb and PDLIM4. CONCLUSION The epigenetic r...
Wnt signaling negatively regulates adipocyte differentiation, and ectopic expression of Wnt-1 in 3T3-L1 cells induces several downstream molecules of Wnt signaling, including Wnt-1 inducible signaling pathway protein (WISP)-2. In this study, we examined the role of WISP-2 in the process of adipocyte differentiation using an in vitro cell culture system. In the differentiation of 3T3-L1 cells, WISP-2 expression was observed in growing cells and declined thereafter. In the mitotic clonal expansion phase of adipocyte differentiation, WISP-2 expression was transiently down-regulated concurrently with up-regulation of CCAAT/enhancer-binding protein d expression. Treatment of 3T3-L1 cells in the differentiation medium with lithium, an activator of Wnt signaling, inhibited the differentiation pro...
Ex vivo expanded peripheral blood progenitor cells (PBPC) have been shown to provide rapid neutrophil engraftment, and in some patients, to eliminate neutropenia after transplantation to support high-dose chemotherapy. However, the effect of expansion culture on stem cell content and potential loss of stem cells caused by induction of differentiation remains a concern. We have transplanted 21 patients with breast cancer with expanded autologous PBPC, with 11 patients receiving expanded PBPC as their sole hematopoietic cell source. In these studies, the CD34+ cells were selected and cultured for 10 days in defined media containing 100 ng/mL each of recombinant human stem cellfactor (rhSCF), recombinant human granulocyte colony stimulating factor (rhG-CSF), and recombinant human megakaryocy...
Abstract Human mesenchymal stem cells (hMSCs) may be used for therapeutic applications. Culture conditions such as the serum source may impact on cell quality and the onset of replicative senescence. We have examined the effect of culturing hMSCs in autologous serum (AS) versus fetal bovine serum (FBS) on factors involved in in vitro replicative senescence. hMSCs from four donors were cultured in 10% FBS or 10% AS until they reached senescence. Cells were harvested at early passage and near senescence to study factors known to be involved in cellular senescence. The number of population doublings till senescence was similar for cells cultured in FBS, but varied greatly for hMSCs cultured in AS. FBS cells accumulated in S phase of cell cycle. This could not be explained by increased express...
The study of blocking factors requires in vitro assay of cell mediated immunity that parallels the in vivo response. By microcytotoxicity testing, progressor and immune peripheral blood lymphocytes...Full Text Available
Epidermal growth factor receptor (EGFR) kinase domain mutations hyperactivate the kinase and confer kinase addiction of the non-small-cell lung cancer (NSCLC) tumor...Full Text Available
Epidermal growth factor receptor (EGFR) related therapies – mainly tyrosine kinase inhibitors (TKIs) such as erlotinib and gefitinib, but also monoclonal antibodies targeting EGFR, for example,...Full Text Available
To investigate the fate of intrinsic factor and cobalamin during cobalamin absorption, we incubated enterocytes isolated from guinea pig ileum for periods of up to 30 min with 57Co-labeled...Full Text Available
In response to oxidative stress, the transcription factor NF-E2-related factor 2 (Nrf2) controls the fate of cells through transcriptional upregulation of antioxidant response element (ARE)-bearing...Full Text Available
OBJECTIVEPreimplantation factor (PIF) is a novel, 15 amino acid peptide, secreted by viable embryos. This study aims to elucidate PIF’s effects in human endometrial...Full Text Available
Aim: Several studies have investigated the expression of the cytokeratins (CKs), vimentin, the epithelial growth factor receptor (EGFR), the oestrogen receptor (ER), and the progesterone...Full Text Available
... s the matter with Kansas?Legislative debates over stem cell research in Kansas and MassachusettsBonnie StabileSchool of Public Policy, ... examines the contextual factors shaping legislative debates affec...
The fungal pathogen Candida albicans is one of the leading causative agents of death in immunocompromised individuals. It harbors an arsenal of cell wall anchored factors that are implicated...Full Text Available
Epidermal growth factor receptor (EGFR)-specific monoclonal antibodies predominantly inhibit colorectal cancer (CRC) growth by interfering with receptor signaling. Recent analyses have shown that patients...Full Text Available
Constitutive activation of the transcription factor Stat5 in hematopoietic stem/progenitor cells leads to various hematopoietic malignancies including myeloproliferative neoplasm (MPN). Our recent study...Full Text Available
Transcription factors drive organogenesis, from the initiation of cell fate decisions to the maintenance and implementation of these decisions. The Drosophila embryonic salivary gland...Full Text Available
On agar plates, daughter cells of Escherichia coli mutually slide and align side-by-side in parallel during the first round of binary fission. This phenomenon has been previously attributed...Full Text Available
Genome endoreduplication during mammalian development is a rare event for which the mechanism is unknown. It first appears when fibroblast growth factor 4 (FGF4) deprivation induces differentiation...Full Text Available
Activation of beta-adrenergic or muscarinic acetylcholine receptors expressed in transfected cells or epidermal growth factor receptors in human keratinocytes produces 15% to 200% changes in cellular...Full Text Available
Cocaine is a worldwide used drug and its abuse is associated with physical, psychiatric and social problems. The mechanism by which cocaine causes neurological damage is very complex and involves several...Full Text Available
Bacterial pathogens use virulence strategies to invade epithelial barriers, but active processes of epithelial cells may also contribute to the endocytosis of microbial particles. To focus on the latter,...Full Text Available
A goal of our research is to identify biochemical factors that underlie the susceptibility of bone marrow cell populations to benzene metabolites so as to develop a mechanistically based chemoprotective...Full Text Available
Among the several rotenoids, amorphigenin is isolated from the leaves of Amopha Fruticosa and it is known that has anti-proliferative effects and anti-cnacer effects in many cell types....Full Text Available
... After formation of the monolayer (usually in 48 hours), the growth medium was poured off, and the cells washed twice with a Henkes solution and ...
Glypican-3 (GPC3), a membrane-bound heparan sulfate proteoglycan, is found to be overexpressed in hepatocellular carcinoma (HCC). The purpose of the present study was to investigate the possible role of GPC3 in the development of HCC. In this study, RNA interference (RNAi) with a GPC3 small hairpin RNA (GPC3 shRNA) was used to identify the effects of GPC3 on the regulation of malignant behaviors of HCC. MHCC97-H, a highly metastatic human HCC cell line in which GPC3 mRNA and protein levels were detected as the highest among the 4 HCC cell lines assessed in this study, and was thus selected as a cell model for in vitro and in vivo experiments. The results showed that down-regulation of GPC3 can significantly inhibit the proliferative and invasive ability of MHCC97-H. Compared with the parental HCC cells, GPC3-silenced cells exhibited ...
The work scope of 'Biological Research for the Radiation Protection' had contained the research about ornithine decarboxylase and its controlling proteins, thioredoxin, peroxiredoxin, S-adenosymethionine decarboxylase, and glutamate decarboxylase 67KD effect on the cell death triggered ionizing radiation and H_2O_2(toxic agents). In this study, to elucidate the role of these proteins in the ionizing radiation (or H_2O_2)-induced apoptotic cell death, we utilized sensesed (or antisensed) cells, which overexpress (or down-regulate) RNAs associated with these proteins biosynthesis, and investigated the effects of these genes on the cytotoxicity caused by ionizing radiation and H_2O_2(or paraquat). We also investigated whether genisteine(or thiamine) may enhance the cytotoxic efficacy of tumor cells caused by ionizing radiation (may enhance the preventing effect radiation or ...
The effects of atrial natriuretic peptide (ANP), oxytocin (OT) and vasopressin (AVP) on guanylate cyclase activity and cyclic GMP accumulation were examined, since these hormones appear to be intimately associated with blood pressure and intravascular volume homeostasis. ANP was found to increase cyclic GMP accumulation in ten cell culture systems, which were derived from blood vessels, adrenal cortex, kidney, lung, testes and mammary gland. ANP receptors were characterized in intact cultured cells using {sup 125}I-ANP{sub 8-33}. Specific {sup 125}I-ANP binding was saturable and of high affinity. Scratchard analysis of the binding data for all cell types exhibited a straight line, indicating that these cells possessed a single class of binding sites. Despite the presence of linear Scatchard plots, these studies demonstrated that cultured cells possess two functionally and physically ...
Abstract This study aimed at developing a suitable cryopreservation protocol for embryonic stem (ES)-like cells of a tiny freshwater fish Leopard danio (Brachydanio frankei). Embryonic stem (ES)-like cells derived from blastomeres of the early blastulae stage of the developing embryo were cultured in vitro in a medium containing Leibowitz-15 supplemented with 10% foetal bovine serum, leopard danio embryo extract, sodium bicarbonate, sodium selenite, basic fibroblast growth factor, epidermal growth factor and leukaemia inhibitory factor. The ES-like cells showed properties similar to ES cells in other species. They were morphologically small, round to polygonal and present in patches and extensively expressed alkaline phosphatase and stage-specific embryonic antigen. The toxicity and chilli...
Maintenance of genomic integrity in embryonic cells is pivotal to proper embryogenesis, organogenesis and to the continuity of species. Cultured mouse embryonic stem cells (mESCs), a model for early embryonic cells, differ from cultured somatic cells in their capacity to remodel chromatin, in their repertoire of DNA repair enzymes, and in the regulation of cell cycle checkpoints. Using 129XC3HF1 mESCs heterozygous for Aprt, we characterized loss of Aprt heterozygosity after exposure to ionizing radiation. We report here that the frequency of loss of heterozygosity mutants in mESCs can be induced several hundred-fold by exposure to 5-10Gy of X-rays. This induction is 50-100-fold higher than the induction reported for mouse adult or embryonic fibroblasts. The primary mechanism underlying the...
Many aspects of cellular motility and mechanics are cyclic in nature such as the extension and retraction of lamellipodia or filopodia. Inherent to the cycles of extension and retraction that test the environment is the production of mechano-chemical signals that can alter long-term cell behavior, transcription patterns, and cell fate. We are just starting to define such cycles in several aspects of cell motility, including periodic contractions, integrin cycles of binding and release as well as the normal oscillations in motile activity. Cycles of local cell contraction and release are directly coupled to cycles of stressing and releasing extracellular contacts (matrix or cells) as well as cytoplasmic mechanotransducers. Stretching can alter external physical properties or sites exposed b...
In mammals and insects, paracellular blood barriers isolate the nervous system from the rest of the animal. Glia and accessory cells of the nervous system use pumps, channels, cotransporters, and exchangers collectively to maintain the extracellular ion environment and osmotic balance in the nervous system. At present, the molecular mechanisms that regulate this process remain unclear. In humans, loss of extracellular ion and volume regulation in the nervous system poses serious health threats. Drosophila is a model genetic organism with a proven track record for uncovering molecular mechanisms relevant to human health and disease. Here, we review what is known about extracellular ion and volume regulation in larval abdominal nerves, present some new data about the impact of neural activity on the extracellular environment, and relate the findings to mammalian systems. Homologies have been found at the ...
Mutations in transcription factors hepatocyte nuclear factors (HNF)-1#alpha# and HNF-1#beta# cause maturity-onset diabetes of the young (MODY) types 3 and 5, respectively. HNF-1#alpha# and HNF-1#beta# mutations are well studied in some tissues, but the mechanism by which HNF-1#alpha# and HNF-1#beta# mutations affect sucrase-isomaltase (SI) transcription in the small intestine is unclear. We studied the effects of 13 HNF-1#alpha# mutants and 2 HNF-1#beta# mutants on human SI gene transcription, which were identified in subjects with MODY3 and MODY5, respectively. Transactivation activity of 11 HNF-1#alpha# and 2 HNF-1#beta# mutants was significantly lower than that of wild (wt)-HNF-1#alpha# and wt-HNF-1#beta#. Furthermore, in co-expression studies with mutant (mu)-HNF-1#alpha#/ wt-HNF-1#beta# and wt-HNF-1#alpha#/mu-HNF-1#beta#, the combination of mu-HNF-1#alpha# (P379fsdelCT and T539fsdelC)/wt-HNF-1#beta# impaired SI transcription, but the ...
1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) is an anti-inflammatory agent with a propenone moiety and chemically synthesized recently. In this study, we examined the chemopreventive effect of FPP-3 on 7,12-dimethylbenz[a]anthracene (DMBA)-induced genotoxicity in MCF-7 cells. FPP-3 reduced the formation of the DMBA-DNA adduct. DMBA-induced CYP1A1 and CYP1B1 gene expression and enzyme activity were inhibited by FPP-3. It inhibited DMBA-induced aryl hydrocarbon receptor (AhR) transactivation and DMBA-inducible nuclear localization of the AhR. Induction of detoxifying phase II genes by chemopreventive agents represents a coordinated protective response against oxidative stress and neoplastic effects of carcinogens. Transcription factor NF-E2 related factor 2 (Nrf2) regulates antioxidant response element (ARE) of phase II detoxifying and antioxidant enzymes, such as glutathione S-transferase (GST) and ...
Hypoxia causes abnormal neonatal pulmonary artery remodeling (PAR) and inhibition of alveolar development (IAD). Transforming growth factor (TGF)-β is an important regulator of lung development...Full Text Available
RIN proteins serve as guanine nucleotide exchange factors for Rab5a. They are characterized by the presence of a RIN homology domain and a C-terminal Vps9 domain. Currently three family members have...Full Text Available
The goal of this lecture is to give an overview of important concepts connected to organisational factors and to provide an understanding of mechanisms by which they can contribute to safe or unsafe behaviour of people. The lecture gives examples of ways to organise work, organisational deficiencies and good practices applied in safety oriented organisations. The lecture also gives an introduction to international work and Finnish national regulation connected to organisation and management. (orig.)
The expression status of the estrogen receptor alpha (ERα) and that of the epidermal growth factor receptor Her-2/neu frequently correlate inversely in breast cancers. While ERα-dependent...Full Text Available
The human causal factors for all human error licensing operational events on Daya Bay nuclear power station since 1993 to 2003 are categorized, the trend of these causal factors is analyzed. The emphasis is placed on analyzing the deficiencies on complying with and executing regulations and procedures. The results provide directional reference for nuclear power station to improve human performance. (author)
Depth dose distributions for protons in the energy range from 2 to 600 MeV have been calculated by Monte Carlo and analytical methods. The dependence on energy of Maximum Dose Equivalent (MDE), quality factor and isotropic factor recommended for practical use are presented. The problems connected with regulation of maximum permissible proton fluxes are discussed. (author).
Epidermal growth factor (EGF) stimulates adenylyl cyclase in the heart via activation of the stimulatory GTP-binding protein Gs. Therefore, employing peptides corresponding to regions in the cytosolic...Full Text Available
Arf GTPases control vesicle formation from different intracellular membranes and are regulated by Arf guanine nucleotide exchange factors (GEFs). Outside of their conserved catalytic domains, known...Full Text Available
BackgroundmicroRNAs (miRNAs) are small non-coding RNAs that are frequently involved in carcinogenesis. Although many miRNAs form part of integrated networks, little information is...Full Text Available
To analyze the proposed growth-inhibitory function of wild-type p53, we compared simian virus 40 (SV40) DNA replication in primary rhesus monkey kidney (PRK) cells, which express wild-type p53, and...Full Text Available
The primary extrusion of Na+ from Mycoplasma gallisepticum cells was demonstrated by showing that when Na+-loaded cells were incubated with both glucose (10 mM) and the uncoupler SF6847 (0.4 microM),...Full Text Available
In t(15;17) acute promyelocytic leukemia, all-trans retinoic acid (RA) induces leukemic cell maturation in vitro and remission in acute promyelocytic leukemia patients, but in vivo treatments invariably...Full Text Available
Programmed cell death (PCD) is triggered when Pto, a Ser-Thr protein kinase, recognizes either the AvrPto or AvrPtoB effector from Pseudomonas syringae pv tomato. This...Full Text Available
Inhibition of large conductance calcium-activated potassium (BKCa) channels mediates, in part, oxygen sensing by carotid body type I cells. However, BKCa channels remain active...Full Text Available
2,4-Dichlorophenoxyacetic acid (2,4-D) promotes the accumulation of tryptophan-derived indole-3-acetic acid (IAA) in carrot cell cultures during callus proliferation by a biosynthetic pathway that is...Full Text Available
Hematopoietic stem cells are resistant to HIV-1 infection. Here, we report a novel mechanism by which the cyclin-dependent kinase inhibitor (CKI) p21Waf1/Cip1/Sdi1 (p21), a known regulator...Full Text Available
P2X1 receptors for ATP contribute to signalling in a variety of cell types and following stimulation undergo rapid desensitisation (within 1 s), and require ∼5 min to recover. In HEK293 cells...Full Text Available
The docking protein p130Cas is a prominent Src substrate found in focal adhesions (FAs) and is implicated in regulating critical aspects of cell motility including FA disassembly and protrusion of the...Full Text Available
BackgroundThe differentiation of CD8+ T lymphocytes following priming of naïve cells is central in the establishment of the adaptive immune response. Yet, the...Full Text Available
T-cell activation requires the influx of extracellular calcium, although mechanistic details regarding such activation are not fully defined. Here, we show that P2X7 receptors play a key...Full Text Available
The ζ chain-associated 70-kDa protein (ZAP-70) of tyrosine kinase plays a critical role in T cell receptor-mediated signal transduction and the immune response. A high level of ZAP-70 expression...Full Text Available
Glycyrrhiza glabra root is one of the common traditional Chinese medicines and used as flavoring and sweetening agents for tobaccos, chewing gums, candies, toothpaste and beverages. While glycyrrhizin is one of the main components in the extract of G. glabra root and has been characterized, the other components have not been well characterized. The mechanism of growth activation of breast cancer MCF-7 cells, including the activation of Erk1/2 and Akt, and the transcriptional regulation of estrogen-responsive genes, was examined by means of sulforhodamine B, luciferase reporter gene, real-time RT-PCR and Western blotting assays after the induction of the cells with the extract of G. glabra root. The extract has similar activity to that induced by 17b-estradiol (E2), although glycyrrhizin di...
Inhibition of the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway is an appealing method for decreasing the immunoresistance and augmenting T cell-mediated immunotherapy. A major impediment to this strategy is the impact of conventional PI3K/mTOR pathway inhibitors on T cell function. In particular, rapamycin, is a well-known immunosuppressant that can decrease the activity of the PI3K/mTOR pathway in tumor cells, but also has a profound inhibitory effect on T cells. Here we show that Honokiol, a natural dietary product isolated from an extract of seed cones from Magnolia grandiflora, can decrease PI3K/mTOR pathway-mediated immunoresistance of glioma, breast and prostate cancer cell lines, without affecting critical proinflammatory T cell functions. Specifically, we show that at doses sufficient to down-regulate ...
The present volume on modeling of batteries and fuel cells discusses the significance of the effectiveness factor for flooded porous electrodes, active pore distribution spectroscopy for characterizing porous battery electrodes, the agglomerate model for porous electrodes, and dynamic-performance measurements of battery cells for electric vehicles and other applications. Attention is given to mathematical modeling of a primary zinc/air battery, mathematical modeling of Grace Li-TiS2 cells, modeling of electrocrystallization processes in battery systems, and rotating disk electrode studies in molten Li/K carbonate eutectic. Topics addressed include the variability of nickel oxide cathode dissolution in molten carbonate fuel cells, water transport properties of fuel cell ionomers, modeling water content effects in polymer electrolyte fuel ...
Methods for improving the sensitivity of scintillation cells for radon concentration measurements were studied with emphasis on improving light collection efficiency. This allows the length and hence the volume of the cell to be increased. Variables studied were choice of scintillator material, its method of application and thickness, length of cell, cell material, type and configuration of reflectors, choice of photomultipliers, and factors affecting background. Response from various areas of the cell surface was studied with an alpha source and with radon filling. Coating the window with phosphor was found to be counter-productive. The optimum results obtained were with the inside of the cell (other than the window) covered with a thick layer of ZnS(Ag), or with a thick layer of reflective material coated with a thin layer of phosphor. ...
Methods for improving the sensitivity of scintillation cells for radon concentration measurements were studied with emphasis on improving light collection efficiency. This allows the length and hence the volume of the cell to be increased. Variables studied were choice of scintillator material, its method of application and thickness, length of cell, cell material, type and configuration of reflectors, choice of photomultipliers, and factors affecting background. Response from various areas of the cell surface was studied with an alphy source and with radon filling. Coating the window with phosphor was found to be counter-productive. The optimum results obtained were with the inside of the cell (other than the window) covered with a thick layer of ZnS(Ag), or with a thick layer of reflective material coated with a thin layer of phosphor. ...
We report herein that trefoil factor 3 (TFF3) is oncogenic and mediates anti-estrogen resistance in human mammary carcinoma. Forced expression of TFF3 in mammary carcinoma cells increased cell proliferation...Full Text Available
Glycosaminoglycan synthesis by two subpopulations of a mouse mammary tumor cell line was compared. The two sublines express distinctly different growth characteristics in vitro and in vivo which indicate differences in growth regulation. Newly made glycosaminoglycans were recovered from the culture media, the cell surfaces, and residual cellular material. The cell population which grows more aggressively in vivo (+SA subline, a subline that grows in soft agarose) incorporated about 8 times more (/sup 14/C)glucosamine per cell into total glycosaminoglycans than did the slower-growing population (-SA subline, which does not grow in soft agarose). Appropriate control experiments indicated that the apparent difference in rates of synthesis was not due to discrepancies in glucosamine uptake. The main residual cellular molecule labeled was heparan sulfate, but the predominant molecule at ...
Abstract: The ability of melatonin as a potent antioxidant was used as a rationale for testing its antiapoptotic ability in normal cells. Recently, melatonin was shown to possess proapoptotic action by increasing reactive oxygen species in certain cancer cells. The modification of radiation-induced apoptosis by melatonin and the expression of apoptosis-associated upstream regulators were studied in normal mice splenocytes and Jurkat T leukemia cells. C57BL/6 mice were exposed to a single whole body X-ray radiation dose of 2 Gy with or without 250 mg/kg melatonin pretreatment. The Jurkat cells were divided into four groups of control, 1 mm melatonin alone, 4 Gy irradiation-only and melatonin pretreatment before irradiation. The highest level of apoptosis in the normal splenic white pulp was...
Nerve growth factor (NGF), a survival factor for neurons enforces pain by sensitizing nociceptors. Also in the pancreas, NGF was associated with pain and it can stimulate the proliferation of pancreatic cancer cells. Hepatic stellate cells (HSC) respond to NGF with apoptosis. Transforming growth factor (TGF)-b, one of the strongest pro-fibrogenic activators of pancreatic stellate cells (PSC) induced NGF and its two receptors in an immortalized human cell line (ihPSC) and primary rat PSC (prPSC) as determined by RT-PCR, western blot, and immunofluorescence. In contrast to HSC, PSC expressed both NGF receptors, although p75NTR expression was weak in prPSC. In contrast to ihPSC TGF-b activated both Smad signaling cascades in prPSC. NGF secretion was diminished by the activin-like kinase (ALK)...
Macroautophagy is a multistep, vacuolar, degradation pathway terminating in the lysosomal compartment, and it is of fundamental importance in tissue homeostasis. In this review, we consider macroautophagy in the light of recent advances in our understanding of the formation of autophagosomes, which are double-membrane-bound vacuoles that sequester cytoplasmic cargos and deliver them to lysosomes. In most cases, this final step is preceded by a maturation step during which autophagosomes interact with the endocytic pathway. The discovery of AuTophaGy-related genes has greatly increased our knowledge about the mechanism responsible for autophagosome formation, and there has also been progress in the understanding of molecular aspects of autophagosome maturation. Finally, the regulation of au...
S100A4, a member of the Ca(2+)-activated S100 protein family, regulates the motility and invasiveness of cancer cells. Moreover, high S100A4 expression levels correlate with poor patient survival in several cancers. Although biochemical, biophysical, and structural data indicate that S100A4 is a noncovalent dimer, it is unknown if two functional S100A4 monomers are required for the productive recognition of protein targets and the promotion of cell invasion. To address this question, we created covalently linked S100A4 dimers using a glycine rich flexible linker. The single-chain S100A4 (sc-S100A4) proteins exhibited wild-type affinities for calcium and nonmuscle myosin-IIA, retained the ability to regulate nonmuscle myosin-IIA assembly, and promoted tumor cell invasion when expressed in S100A4-deficient colon carcinoma cells. Mutation of the two calcium-binding ...
We have used a cell-free polymerase I transcription system derived from HeLa cells to study the regulation of human rRNA synthesis. Analysis of deletion mutants spanning the start site of transcription at nucleotide +1 indicates that the control region affecting initiation of human rRNA synthesis is contained within sequences from nucleotides -158 to +18. This promoter region can be subdivided into (i) a central segment of approximately 40 base pair that is required for transcription and (ii) flanking sequences that influence the efficiency of transcription in vitro. We have examined the in vitro transcriptional activity of the human extract under various conditions that are thought to modulate rRNA synthesis in vivo. Cell-free extracts prepared from HeLa cells infected with adenovirus 2 synthesize human rRNA at levels greatly decreased relative to uninfected ...
The promising use of mesenchymal stromal cells (MSC) in regenerative technologies accounts for necessity of detailed study of their physiology. Proliferation and differentiation of multipotent cells often involve changes in their metabolic state. In the present study, we analyzed the expression of ATP-sensitive potassium (K"A"T"P) channels in MSC and upon in vitro differentiation. K"A"T"P channels are present in many cells and regulate a variety of cellular functions by coupling cell metabolism with membrane potential. Kir6.1, Kir6.2 and SUR2A were expressed in undifferentiated MSC, whereas SUR2B and SUR1 were not detected on cDNA and protein level. Upon adipogenic differentiation Kir6.1 and SUR2A showed a significant reduction of the amount of mRNA by 84% and 95%, respectively, whereas Ki...
This paper analyzes the diffusion of mobile telecommunications services in Vietnam and examines how telecommunications regulation and potential substitute/complement services affect the growth of the number of mobile telephone subscribers. Using a logistic diffusion model, it is found that fixed telephone services are a complement while data services have a negative relation to mobile telephone services in Vietnam. As for regulation, the policy of introducing competition has been found to be the most effective in influencing the adoption of mobile services. Another important result is that the estimated potential market is roughly 76% of the total population. The findings suggest that suitable regulation that guarantees competition in the mobile telecommunications market in a developing co...
This document includes the following topics: Background; Data Collection; Scope/Applicability of the Proposed Regulation; Description of the Industry; Industry Subcategorization; Pollutants of Concern for the Centralized Waste Treatment Industry; Pollutants Selected for Regulation; Wastewater Treatment Technologies; Regulatory Options Considered and Selected for Basis of Regulation; Long-Term Averages, Variability Factors, and Limitations and Standards; Cost of Treatment Technologies; Pollutant Loading and Removal Estimates; Non-Water Quality Impacts; Implementation; Analytical Methods and Baseline Values; List of Definitions; List of Acronyms; Appendix A--Pollutant Groups; Appendix B--Listing of Characerization Data From Non-Hazardous Oils Facilities; Appendix C--Listing of Daily Influent and Effluent Measuements; Appendix D--Facility-Specific Compliance Costs; Appendix E--Attachements to Chapter 10; ...
Growth differentiation factor-9 (GDF-9), an oocyte-secreted member of the transforming growth factor β superfamily, progesterone receptor, cyclooxygenase 2 (Cox2; Ptgs2), and the EP2 prostaglandin...Full Text Available
Abstract. Objective: Lapatinib (Tykerb, GW572016), a potent inhibitor of the catalytic activities of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) (ErbB2), inhibits population growth of selected EGFR and HER2 overexpressing cell lines. Previous studies with a small number of cell lines suggest a correlation between overexpression of EGFR and/or HER2 and sensitivity to growth inhibition by lapatinib; however, the precise determinants of lapatinib selectivity for tumour and/or other cells remain unclear. Materials and methods: To clarify the determinants of its selectivity in cultured cells, lapatinib-induced cell population growth inhibition and relative EGFR and HER2 protein expression were quantified in 61 different human tumour cell lines fro...
Investigation of selective emitter solar cells has been undertaken using both device fabrication and accurate two-dimensional simulation program. Our results show that selective emitter solar cells exhibit a relatively low fill factor because of minority carriers crowding at the lateral junction. It is also found that carrier recombination in the space-charge region of the lateral junction limits open-circuit voltage improvements
Objectives1) To establish a protocol for transfection of immortalised type I cells with SiRNA and its effect on cell viability; 2) To optimise silencing of genes involved in endocystosis using SiRNA and confirm successful transfection with western blotting; 3) To investigate the effect of gene silencing on uptake of flourescently-labelled latex nanoparticles.DescriptionTo investigate the mechanisms of particle uptake.
Sphere-forming abilities in culture condition are considered a hallmark of cancer stem-like cells, which represents tumor cell invasiveness and stem-like characteristics. We aimed to show that the sphere-forming subpopulation of human malignant melanoma cell line WM-266-4 acts differently to zebrafish embryo extracts compared with their bulk counterpart. Spheres were maintained in neural stem cell culture conditions. The embryos of zebrafish at specific developmental stages were collected and the extracts were purified under 100 kDa. Spheres were treated with embyo extracts and proliferation assay and immunocytochemistry were conducted. Spheroid cells expressed nestin and epidermal growth factor receptor (EGFR) but not melanoma antigen recognized by T-cells (MART)1, indicating their stem-l...
The key factors of enzymatic lysis of cells are the interaction between the enzyme and the cell - catalytic and non-catalytic adsorption of enzyme on cell surface. Here, the studies of lysis of intact Escherichia coli cells by chicken egg white lysozyme were performed. It was found that the ionic strength has a dual effect onto the system. On the one hand, the desorption constant of the enzyme increases with the increase of the solution ionic strength, which results in a better enzyme performance. On the other hand, due to the higher osmosis, the cell lysis rate decreases with the increasing of ionic strength of the system. It was found that pH 8.6 and 30mM NaCl are optimal conditions for lysis of E. coli cells by lysozyme.
The origin of the epithelial and myoepithelial cells in the human breast has not been delineated. In this study we have addressed whether luminal epithelial cells and myoepithelial cells are vertically connected, i.e., whether one is the precursor for the other. We used a primary culture assay allowing preservation of basic phenotypic traits of luminal epithelial and myoepithelial cells in culture. The two cell types were then separated immunomagnetically using antibodies directed against lineage-specific cell surface antigens into at best 100% purity. The cellular identity was ascertained by cytochemistry, immunoblotting, and 2-D gel electrophoresis. Luminal epithelial cells were identified by strong expression of cytokeratins 18 and 19 while myoepithelial cells were recognized by expression of vimentin and ...
Bone marrow is one of the most radiosensitive organs. Irradiation causes a marked decrease in the total number of hematopoietic cells in the bone marrow. The reticular meshwork structure of marrow stromal cells, however, is relatively resistant to irradiation. Unimpaired stromal cell structure has been thought to be a prerequisite for the repopulation of hematopoietic cells during recovery from the effects of irradiation. The reticular framework is maintained by cell adhesion apparatuses such as gap junctions. The in vitro radiobiologic survival values of a cloned stromal cell line, H-1/A, were studied (n = 1.8, D0 = 138 cGy). Radiation doses of up to 4000 cGy had no detectable effects on the production of colony-stimulating factor 1. H-1/A cells communicate with each other via gap junctions as determined by the ...
Bone marrow is one of the most radiosensitive organs. Irradiation causes a marked decrease in the total number of hematopoietic cells in the bone marrow. The reticular meshwork structure of marrow stromal cells, however, is relatively resistant to irradiation. Unimpaired stromal cell structure has been thought to be a prerequisite for the repopulation of hematopoietic cells during recovery from the effects of irradiation. The reticular framework is maintained by cell adhesion apparatuses such as gap junctions. The in vitro radiobiologic survival values of a cloned stromal cell line, H-1/A, were studied (n = 1.8, D0 = 138 cGy). Radiation doses of up to 4000 cGy had no detectable effects on the production of colony-stimulating factor 1. H-1/A cells communicate with each other via gap junctions as determined by the ...
Possible factorsregulating phytoplankton variability in the Arabian (Persian) Gulf were analyzed on the basis of satellite observations and meteorological data (1997-2009), including remotely-sensed chlorophyll a concentration (CHL), sea surface temperature, wind, solar radiation, precipitation, and aerosols. Shallow waters of northwestern Gulf influenced by Shatt Al-Arab River discharge were more productive than open Gulf waters, although seasonal CHL patterns in this and other shallow regions looked unrealistic likely because the CHL signal was obscured by bottom reflection. Therefore our further analyses focused on the open Gulf waters, which show a subtropical seasonal CHL cycle with maximum in winter and minimum in spring-summer. This cycle, however, was decoupled from the seasonal e...
It has been proposed that the gastrointestinal tract environment containing high levels of neuroendocrine hormones is important for gut-derived Pseudomonas aeruginosa infections. In this study, we report that the hormone norepinephrine increases P. aeruginosa PA14 growth, virulence factor production, invasion of HCT-8 epithelial cells, and swimming motility in a concentration-dependent manner. Transcriptome analysis of P. aeruginosa exposed to 500 microM, but not 50 microM, norepinephrine for 7 h showed that genes involved in the regulation of the virulence determinants pyocyanin, elastase, and the Pseudomonas quinolone signal (PQS, 2-heptyl-3-hydroxy-4-quinolone) were upregulated. The production of rhamnolipids, which are also important in P. aeruginosa infections, was not significantly altered in suspension cultures upon exposure to 500 microM norepinephrine but decreased on semisolid surfaces. Swarming motility, a ...
The Drosophila sequence-specific DNA binding protein, Adf-1, is capable of activating transcription of the alcohol dehydrogenase gene, Adh, and is implicated in the transcriptional control of other developmentally regulated genes. We have cloned the cDNA encoding Adf-1 by generating specific DNA probes deduced from partial amino acid sequence of the protein. Several cDNA clones encoding an extended open reading frame were isolated from a phage lambda library. The complete amino acid sequence of Adf-1 deduced from the longest cDNA reveals structural similarities to the putative helix-turn-helix DNA binding motif of Myb and Myb-related proteins. DNA sequence analysis of genomic clones and Northern blot analysis of mRNA suggest that Adf-1 is a single-copy gene encoding a 1.9-kb transcript. Purified recombinant Adf-1 expressed in Escherichia coli binds specifically to Adf-1 recognition sites and activates transcription of a synthetic Adh promoter in vitro in a manner ...
A rat thyrotropin (thyroid-stimulating hormone, TSH) receptor cDNA was isolated that encoded a protein of 764 amino acids, M_r 86,528. Transfection of the cDNA caused COS-7 cells to develop a TSH-sensitive adenylate cyclase response and the ability to bind "1"2"5I-labeled TSH; both activities were similar to those of rat FRTL-5 thyroid cells and not duplicated by lutropin. The gene represented by the cDNA was assigned to mouse chromosome 12 and human chromosome 14. Northern analyses identified two species of mRNA, 5.6 and 3.3 kilobases, in FRTL-5 thyroid cells; the transcripts appeared to differ only in the extent of their 3' noncoding sequences. There were minimal amounts of the two mRNAs in rat ovary, and neither was detected in RNA preparations from rat testis, liver, lung, brain, spleen, and FRT thyroid cells, which do not have a functional TSH receptor. TSH decreased both mRNA species 3- to 4-fold ...
Many hormones elicit effects on target cells by stimulating the enzyme phospholipase-C, which catalyzes the hydrolysis of phosphoinositides to the intracellular second messengers diacylglycerol and inositol phosphates. The present study examined the roles of FSH and guanine nucleotide-binding proteins (G-proteins) in regulating the hydrolysis of phosphoinositides in Sertoli cells. Sertoli cell cultures prepared from 16- to 18-day-old rats were incubated for 24 h with myo-[2-3H] inositol to label endogenous phospholipids. Treatment of cells from 0.5-20 min with preparations of ovine FSH ranging in potency from 1-60 times that of NIH FSH S1 did not affect accumulation of inositol phosphates. Levels of total [3H]inositol phosphates [[3H]inositol mono-, di-, and triphosphates (IP, IP2, and IP3)] in FSH-treated cultures was 75-120% the levels in control cultures over the various time ...
Bioethics--the study of ethical issues in science and medicine--has grown to become a significant academic and service-oriented discipline with its own research centers, conferences, journals, and degree programs. As these issues have moved to the center of public debate, the law has assumed an increasingly important place in the discipline of bioethics. Today, embryonic stem cell research stands out as a critically important issue about which the U.S. has neither ethical consensus nor clear, comprehensive regulation. The ethical debate centers on the fact that stem cell research involves the destruction of very early human embryos. This article provides a brief scientific background followed by a discussion of key ethical and legal/regulatory issues that surround embryonic stem cell research.
Transforming growth factor beta (TGF-@b) has a crucial role in the differentiation of ectodermal cells to neural or epidermal precursors. TGF-@b and bone morphogenetic protein molecules (BMPs) are involved in many developmental processes, including cell proliferation and differentiation, apoptosis, mitotic arrest and intercellular interactions during morphogenesis. Additionally, the failure of central thymic tolerance mechanisms, leading to T cells with a skewed autoreactive response, is being described as a contributor in inflammatory processes in autoimmune diseases such as multiple sclerosis. Since TGF-@b and BMP proteins are crucial for the development of the neural system and the thymus, as well as for the differentiation of T cells, it is essential to further investigate their role i...
Transdifferentiation of an individual's own cells into functional differentiated cells to replace an organ's lost function would be a personalized approach to therapeutics. In this two part series, we will describe the progress toward establishing functional transdifferentiated adrenal cortical cells. In this article (Part 1), we describe adrenal development and function, and discuss genes involved in these processess and selected for use in our pilot studies of transdifferentiation that are presented in the second article (Part 2).
The various factors that affect the open-circuit voltage ([ital V][sub oc]) of a two-terminal GaInP[sub 2]/GaAs tandem cell are examined. These include a) an anomalous problem associated with the GaAs bottom cell and b) back surface passivation of the thin GaInP[sub 2] top cell. Solutions to these problems are presented and yield tandem [ital V][sub oc]s close to the practical theoretical limits.
The authors have identified a protein present only in erythroid cells that binds to two adjacent sites within an enhancer region of the chicken {beta}-globin locus. Mutation of the sites, so that binding by the factor can no longer be detected in vitro, leads to a loss of enhancing ability, assayed by transient expression in primary erythrocytes. Binding sites for the erythroid-specific factor (Eryf1) are found within regulatory regions for all chicken globin genes. A strong Eryf1 binding site is also present within the enhancer of at least one human globin gene, and proteins from human erythroid cells (but not HeLa cells) bind to both the chicken and the human sites.
Swelling hemoglobin CC erythrocytes stimulates a ouabain-insensitive K flux that restores original cell volume. Studies were performed with the K analog, "8"6Rb. This volume regulatory pathway was characterized for its anion dependence, sensitivity to loop diuretics, and requirement for Na. The swelling-induced K flux was eliminated if intracellular chloride was replaced by nitrate and both swelling-activated K influx and efflux were partially inhibited by 1 mM furosemide or bumetanide. K influx in swollen hemoglobin CC cells was not diminished when Na in the incubation medium was replaced with choline, indicating Na independence of the swelling-induced flux. Identical experiments with hemoglobin AA cells also demonstrated a swelling-induced increase in K flux, but the magnitude and duration of this increase were considerably less than that seen with hemoglobin CC cells. The increased K flux in ...
A conceptual design of an advanced sodium/sulfur cell for US electric-van applications has been completed. The important design factors included specific physical and electrical requirements, service life, manufacturability, thermal management, and safety. The capacity of this cell is approximately the same as that for the ``PB`` cell being developed by Silent Power Limited (10 Ah). The new cell offers a 50% improvement in energy capacity and nearly a 100% improvement in peak power over the existing PB cells. A battery constructed with such cells would significantly exceed the USABC`s mid-term performance specifications. In addition, a similar cell and battery design effort was completed for an advanced passenger car application. A battery using the van cell would have nearly 3 times the energy ...
Cultures of 3T3-L1 cells were incubated with either 10 ng/ml cholera toxin or 10 ng/ml pertussis toxin from 4 days prior to the initiation of differentiation and throughout the subsequent incubation. Toxin concentrations were sufficient to completely prevent the labelling of alpha-subunits with ["3"2P]NAD"+ and pertussis toxin and to prevent by more than 90% the labelling with ["3"2P]NAD"+ and cholera toxin in membranes prepared from these cells. Neither toxin prevented the differentiation to the adipocyte phenotype. Neither toxin prevented the increases in the relative amounts of G-proteins which occur upon differentiation. Both toxins dramatically decreased the amount of beta-subunits. As measured by quantitative immunoblotting with antisera specific for both the 35 kDa and 36 kDa beta-subunits, levels of beta-subunit were decreased by more than 50% of steady-state level of control cells. Thus, bacterial toxins which ...
CBA/Ca mice were infected by either the intravenous or intraperitoneal route with Mycobacterium microti and the subsequent changes in local macrophage populations examined. Following infection, the number of macrophages increased and they showed greater expression of both MHC Class II molecules. This response was not dependent on viability of the mycobacteria, in contrast to reports with other microorganisms such as Listeria. Studies in sublethally irradiated mice indicated that persistent antigen could give rise to a response after a period of host recovery which was radiation dose dependent. This procedure also highlighted differences in the regulation of different murine class II antigens in vivo, as seen by delayed re-expression of I-E antigens. Macrophage accessory cell function, as assessed by an in vitro T cell proliferation assay, correlated with Ia expression after fixation, but not after indomethacin treatment; ...
The findings reported in this study highlight several important features of the development of hematopoietic stem cells after transplantation into irradiated recipients. First, they demonstrate the existence of a class of primitive multipotential stem cells that can function for a significant portion of the lifetime of a mouse (15 mo). In addition, they clearly show that these primitive stem cells can be infected with recombinant retroviruses and thus would be appropriate targets for gene therapy in somatic tissues. Second, our data indicate that the progeny of some, but not all, of the primitive stem cells have fully expanded into the various hematopoietic lineages by 2 mo after reconstitution. Finally, our analysis of the secondary recipients provides strong evidence suggesting that the primitive stem cell population can actually clonally expand. Our current experiments are aimed ...
The bed nucleus of the stria terminalis (BST) and the medial amygdala (MeA) are anatomically connected sites necessary for chemosensory regulation of social behaviors in rodents. Prairie voles (Microtus ochrogaster) are a valuable model for studying the neural regulation of social behaviors because, unlike many other rodents, they are gregarious, pair bond after copulating, and are biparental. We herein describe sex and species differences in immunoreactivity for tyrosine hydroxylase (TH), the rate-limiting enzyme for catecholamine synthesis, in the BST and MeA. Virgin male prairie voles had a large number of TH-immunoreactive cells in areas analogous to the rat principal nucleus of the BST (pBST) and the posterodorsal medial amygdala (MeAPd). Virgin female prairie voles had far fewer TH-immunoreactive cells in these sites ( approximately 17% of the number of cells as males in the ...
The mammalian placenta consists of different trophoblast cell types that assist in the variety of functions required for the maintenance of pregnancy. In rodents, labyrinthine trophoblasts of the placenta are especially important, because they are capable of differentiating into fused labyrinthine cells, which form the feto-maternal exchange surface. Even though the molecular signals triggering labyrinthine trophoblast differentiation are poorly understood, transforming growth factor-b (TGF-b) has been shown to be present in the placental environment and alter trophoblast development. In this study, we investigated the effects of TGF-b on the differentiation of the labyrinthine trophoblast stem cell lines SM10 and HRP-1. RT-PCR analyses demonstrated that while the molecular expression of l...
Purpose The paired-like homeodomain transcription factor 2 (PITX2) gene encodes a transcription factor controlled by the WNT/Dvl/CTNNB1 and Hedgehog/TGFB pathways in the pathogenesis of colorectal cancer (CRC). Although PITX2 is reportedly involved in various functions, including tissue development by controlling cell growth, its significance in CRC remains unclear. We report our findings regarding abnormal PITX2 expression in human CRC. Methods PITX2 expression was evaluated in 5 human CRC cell lines and 92 primary CRC samples. Cell growth was evaluated after inhibition of PITX2 expression or after exogenous introduction of PITX2. Results PITX2 expression was seen in all the five CRC cell lines. The study of tissue samples indicated that PITX2 expression was significantly higher in cancer...
Studies on the regulation of the enterocytic differentiation of the human colon cancer cell line HT-29, which is differentiated in the absence (Glc"-) but not in the presence of glucose (Glc"+), have recently shown that the post-translational processing of sucrase-isomaltase and particularly its glycosylation vary as a function of cell differentiation. Other studies indicate that in undifferentiated HT-29 Glc"+ cells there is an accumulation of UDP-N-acetylhexosamine, which is involved in the glycosylation process. The purpose of the present work is to investigate whether an overall alteration of protein glycosylation is associated with the inability of HT-29 cells to differentiate. At least three alterations are detected: (i) after a 10-min pulse, the incorporation of D-[2-"3H]mannose in undifferentiated cells is severely reduced, compared to differentiated ...
A rat hepatocyte cell line was shown previously to contain a nuclear pool of free heparan SO/sub 4/ (HS) chains which turns over rapidly. These cells were labeled with /sup 35/SO/sub 4//sup 2 -/ and the steady state levels of (/sup 35/SO/sub 4/)HS in the nucleus were measured under culture conditions chosen to give different cell doubling times (DT's). In each log phase culture growing at a constant rate, the level of nuclear HS did not change as the cell density increased. Rapidly dividing cells had levels of nuclear HS within the range of 30-42 pmol /sup 35/SO/sub 4/ in the nuclear HS/10/sup 6/ cells. However, in cultures with decreased DT's, there was a corresponding decrease in the level of nuclear HS below 30 pmol/10/sup 6/ cells that was proportional to the decrease in the DT. In contrast, when the ...
High salinity is one of the main factors limiting cotton growth and productivity. The genes that regulate salt stress in TM-1 upland cotton were monitored using microarray and real-time PCR (RT-PCR) with samples taken from roots. Microarray analysis showed that 1503 probe sets were up-regulated and 1490 probe sets were down-regulated in plants exposed for 3h to 100mM NaCl, and RT-PCR analysis validated 42 relevant/related genes. The distribution of enriched gene ontology terms showed such important processes as the response to water stress and pathways of hormone metabolism and signal transduction were induced by the NaCl treatment. Some key regulatory gene families involved in abiotic and biotic sources of stress such as WRKY, ERF, and JAZ were differentially expressed. Our transcriptome analysis might provide some useful insights into salt-mediated signal transduction pathways in cotton and offer a ...
Conditioned medium from Sertoli cells, prepared from testes of 20-day-old rats, contains component(s) that inhibit the incorporation of (3H)-thymidine into DNA of peritubular myoid cells (PMC) and inhibit the proliferation of PMC. These components are trypsin-resistant, heat-stable compounds having a molecular weight less than 30,000. The active inhibitory components in Sertoli cell conditioned medium are inactivated by treatment with heparinase, but not by treatment with hyaluronidase or chondroitin sulfate lyases. Addition of heparin or heparan sulfate results in inhibition of DNA synthesis by PMC in a dose-dependent manner, whereas other glycosaminoglycans (GAGs) examined (hyaluronic acid, keratan sulfate, and chondroitin sulfate) have no detectable effects. Heparin and heparan sulfate are unique among GAGs tested in inhibiting the characteristic multilayer growth pattern of PMC following the attainment of confluence in ...
Poncirin, flavanone glycoside, isolated from the fruit of Poncirus trifoliata, has anti-bacterial and anti-inflammatory activities. In this study, the effects of poncirin on the differentiation of mesenchymal stem cells were investigated. The C3H10T1/2 mesenchymal stem cells and primary bone marrow mesenchymal stem cells were studied. In the C3H10T1/2 cells, poncirin prevented adipocyte differentiation, as demonstrated by inhibition of cytoplasm lipid droplet accumulation and peroxisome proliferator-activating receptor-? (PPAR-?) and CCAAT-enhancer-binding protein-? (C/EBP-?) mRNA expression. By contrast, poncirin enhanced the expression of the key osteogenic transcription factors, runt-related transcription factor 2 (Runx2) and transcriptional coactivator with PDZ-binding motif (TAZ). Poncirin also enhanced expression of the osteogenic marker genes including ...
The biological actions of juvenile hormones are well studied; they regulate almost all aspects of an insect’s life. However, the molecular actions of these hormones are not well understood....Full Text Available
Sterol regulatory element-binding protein (SREBP)-1 is a key transcription factor for the regulation of lipogenic enzyme genes in the liver. Polyunsaturated fatty acids (PUFA) selectively suppress hepatic...Full Text Available
In clause it is shown a method optimization of brake of forces in view of a bias road it is established, that in mountain conditions of loss of coupling weight of automobiles than 2-3 times concerning flat conditions therma are more. The degree of use of coupling weight in result use of a regulator of brake forces very much increases also efficiency of brake systems such a kind of automobiles is provided with definition of optimum factor of coupling at which value of loss of coupling weight is provided minimal
The UK Pipelines Safety Regulations require the pipeline operator to ensure that a pipeline, once decommissioned, does not become a source of danger. Elsewhere, Regulatory Authorities require consideration of the possible issues which pipeline decommissioning may raise. This paper considers current practice with respect to pipeline decommissioning and abandonment, and sets out the range of factors which the operator must take into account. (author)
Abstract in english Cytokines are molecules that were initially discovered in the immune system as mediators of communication between various types of immune cells. However, it soon became evident that cytokines exert profound effects on key functions of the central nervous system, such as food intake, fever, neuroendocrine regulation, long-term potentiation, and behavior. In the 80's and 90's our group and others discovered that the genes encoding various cytokines and their receptors are e (more) xpressed in vascular, glial, and neuronal structures of the adult brain. Most cytokines act through cell surface receptors that have one transmembrane domain and which transduce a signal through the JAK/STAT pathway. Of particular physiological and pathophysiological relevance is the fact that cytokines are potent regulators of hypothalamic neuropeptidergic systems that maintain neuroendocrine homeostasis and ...
The effect of the external pH on the intracellular pH in mung bean (Vigna mungo (L.) Hepper) root-tip cells was investigated with the T P nuclear magnetic resonance (NMR) method. The T P NMR spectra showed three peaks caused by cytoplasmic G-6-P, cytoplasmic Psub(i) and vacuolar Psub(i). The cytoplasmic and vacuolar pHs could be determined by comparing the Psub(i) chemical shifts with the titration curve. When the external pH was changed over a range from pH 3 to 10, the cytoplasmic pH showed smaller changes than the vacuolar pH, suggesting that the former is regulated more strictly than the latter. The H -ATPase inhibitor, DCCD, caused the breakdown of the mechanism that regulates the intracellular pH. H -ATPase appears to have an important part in the regulation of the intracellular pH.
The effect of the external pH on the intracellular pH in mung bean (Vigna mungo (L.) Hepper) root-tip cells was investigated with the "3"1P nuclear magnetic resonance (NMR) method. The "3"1P NMR spectra showed three peaks caused by cytoplasmic G-6-P, cytoplasmic Psub(i) and vacuolar Psub(i). The cytoplasmic and vacuolar pHs could be determined by comparing the Psub(i) chemical shifts with the titration curve. When the external pH was changed over a range from pH 3 to 10, the cytoplasmic pH showed smaller changes than the vacuolar pH, suggesting that the former is regulated more strictly than the latter. The H"+-ATPase inhibitor, DCCD, caused the breakdown of the mechanism that regulates the intracellular pH. H"+-ATPase appears to have an important part in the regulation of the intracellular pH. (author).
We tested the hypothesis that the basal release of nitric oxide (NO) from endothelial cells modulates contractile activity in the corpus cavernosum (CC) via inhibition of the RhoA/Rho-kinase signaling...Full Text Available
Matrix metalloproteinase (MMP) plays a crucial role in periodontal disease and is up-regulated by oral Gram-negative, pathogen-derived LPS. In this study, we reported that simvastatin, a 3-hydroxyl-3-methylglutaryl-CoA...Full Text Available
BackgroundWhen eukaryotic cells are deprived of amino acids, uncharged tRNAs accumulate and activate the conserved GCN2 protein kinase. Activated Gcn2p up-regulates the general amino...Full Text Available
Phospholamban (PLB) is a 52-amino acid integral membrane protein that helps to regulate the flow of Ca2+ ions in cardiac muscle cells. Recent structural studies on the PLB pentamer...Full Text Available
LIMD1 is a tumour suppressor gene (TSG) down regulated in ∼80% of lung cancers with loss also demonstrated in breast and head and neck squamous cell carcinomas. LIMD1 is also a candidate TSG...Full Text Available
BackgroundAs EBV-associated gastric cancer has unique features that are different from EBV (-) gastric cancer, EBV is considered to have a key role in gastric carcinogenesis. It...Full Text Available
LRP1 is a type-1 transmembrane receptor that mediates the endocytosis of diverse ligands. LRP1 β-chain proteolysis results in release of sLRP1 that is present in human plasma. In this study,...Full Text Available
Mutations of ephrin B1 in humans result in craniofrontonasal syndrome. Because little is known of the role and mechanism of action of ephrin B1 in bone, we examined the function of osteoblast-produced...Full Text Available
Cadmium (Cd) exposure causes glucosuria (glucose in the urine). Previously, it was shown that Cd exposure of primary cultures of mouse kidney cells (PMKC) decreased mRNA levels of the glucose...Full Text Available
The mechanisms underlying life machinery are still not completely understood. Something is known, something is ?probably? known, other things are still unknown. Scientists all over the world are working very hard to clarify the processes regulating the cell life cycle and bioinformaticians try to support them by developing specialized automated tools. Within the plethora of applications devoted to the study of life mechanisms, tools for the analysis and comparison of biological networks are catching the attention of many researchers. It is interesting to investigate why.
Environmental and occupational exposures to heavy metals such as methylmercury (MeHg) and cadmium (Cd) pose significant health risks to humans, including neurotoxicity. The underlying mechanisms of...Full Text Available
Systemic sclerosis is an autoimmune connective tissue disorder characterized by a widespread microangiopathy, autoimmunity and fibrosis of the skin and of various internal organs. Microangiopathy is characterized by a reduced capillary density and an irregular chaotic architecture that lead to chronic tissue hypoxia. Despite the hypoxic conditions, there is no evidence for a sufficient compensative angiogenesis in SSc. Furthermore, vasculogenesis is also impaired. An imbalance between angiogenic and angiostatic factors might explain the pathogenetic mechanisms of SSc vasculopathy. As far as angiogenic factors are concerned, within the most important are vascular endothelial growth factor (VEGF) and its receptors, platelet derived growth factor (PDGF), transforming growth factor beta (TGF-?), fibroblast growth factor -2 (FGF-2), angiopoietin 1 (Ang-1), stromal ...
The p75 neurotrophin receptor (p75"N"T"R) is a death receptor which belongs to the tumor necrosis factor receptor super-family of membrane proteins. This study shows that p75"N"T"R retarded cell cycle progression by induced accumulation of cells in G0/G1 and a reduction in the S phase of the cell cycle. The rescue of tumor cells from cell cycle progression by a death domain deleted (#DELTA#DD) dominant-negative antagonist of p75"N"T"R showed that the death domain transduced anti-proliferative activity in a ligand-independent manner. Conversely, addition of NGF ligand rescued retardation of cell cycle progression with commensurate changes in components of the cyclin/cdk holoenzyme complex. In the absence of ligand, p75"N"T"R-dependent cell cycle arrest facilitated an increase in apoptotic nuclear fragmentation of the ...
PurposeHeavy metals and other forms of oxidative stress have been implicated as key factors in the formation of age-related cataract in humans. Metallothioneins are...Full Text Available
Strategies to combine aspirated marrow cells with scaffolds to treat connective tissue defects are gaining increasing clinical attention and use. In situations such as large defects where initial...Full Text Available
Purpose: This paper reviews and reassesses the internationally accepted niches or ‘targets’ in bone marrow that are sensitive to the induction of leukaemia and primary...Full Text Available
Cervical cancer is known to metastasize primarily by the lymphatic system. Dissemination through lymphatic vessels represents an early step in regional tumor progression, and the presence of lymphatic...Full Text Available
Osterix (Osx) is a zinc-finger-containing transcription factor that is expressed in osteoblasts of all endochondral and membranous bones. In Osx null ...Full Text Available
BackgroundThe epidermal growth factor receptor (Egfr) with its numerous ligands has fundamental roles in development, cell differentiation and physiology. Dysfunction of the receptor-ligand...Full Text Available
The identification of host cellfactors for virus replication holds great promise for the development of new anti-viral therapies. Recently, high-throughput screening methods have emerged as...Full Text Available
1. One hundred and thirty-two antidromically identified paraventricular (PV) and supraoptic (SO) neurones were studied during milk ejection evoked by the suckling of the young, in thirty-four lactating...Full Text Available
Fibroblast growth factor (FGF) signaling is involved in skeletal development of the vertebrate. Gain-of-function mutations of FGF receptors (FGFR) cause craniosynostosis, premature fusion of the skull,...Full Text Available
BackgroundNF-κB is a survival signaling transcription factor complex involved in the malignant phenotype of many cancers, including squamous cell carcinomas (SCC). The citrus...Full Text Available
Polypeptides exiting the ribosome must fold and assemble in the crowded environment of the cell. Chaperones and other protein homeostasis factors interact with newly translated polypeptides to facilitate...Full Text Available
PurposeTo address the roles of the stromal derived factor-1 (SDF-1) α in the course of experimental corneal neovascularization (CNV).MethodsCNV...Full Text Available
New neurons are generated in the granule cell layer of the dentate gyrus (GCL) throughout adulthood. This process is modulated by many environmental and neurochemical factors. We previously...Full Text Available
During blastocyst formation the segregation of the inner cell mass (ICM) and trophectoderm is governed by the mutually antagonistic effects of the transcription factors Oct4 and Cdx2. Evidence indicates...Full Text Available
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Their discovery in the 1990s provided insights...Full Text Available
BackgroundGATA-2 is a transcription factor required for hematopoietic stem cell survival as well as for neuronal development in vertebrates. It has been shown that specific expression...Full Text Available
Humanin (HN), a 24-residue peptide, was identified as a novel neuroprotective factor and shows anti-cell death activity against a wide spectrum of Alzheimer's disease (AD)-related cytotoxicities, including...Full Text Available
The levels of General Transcription Factor (TF) IIA were examined during mammalian brain development and in rat embryo fibroblasts and transformed cell lines. The large TFIIA subunit paralogues ab and t are largely produced in unsynchronized cell lines, yet only TFIIA ab is observed in a number of differentiated tissue extracts. Steady-state protein levels of the TFIIA t, ab, and g subunits were significantly reduced when human embryonal (ec) and hepatic carcinoma cell lines were stimulated to differentiate with either all-trans-retinoic acid (ATRA) or sodium butyrate. ATRA-treated NT2-ec cells required replating to induce a neuronal phenotype and loss of detectable TFIIA t and g proteins. High levels of TFIIA t, ab, and g and Sp factors were identified in extracts from human fetal and rat...
Investigations into sexual differentiation and pheromone response in the fission yeast Schizosaccharomyces pombe are complicated by the need to first starve the cells of nitrogen. Most mating-related experiments are therefore performed on non-dividing cells. Here we overcome this problem by using two mutants that bypass the nutritional requirements and respond to the M-factor mating pheromone in rich medium. The first mutant lacks the cyr1 gene which encodes adenylate cyclase and these cells contain no measurable amounts of cAMP. When M-factor is added to a growing h+ cyr1- strain it causes a transient G1 arrest of cell division, transcription of mat1-Pm, and elongation of the cells to form shmoos. The second mutant contains the temperature-sensitive pat1-114 allele. At 30 degrees C this mutant was previously shown not only to bypass the ...
Abstract MicroRNAs (miRNAs) play important roles in global gene regulation. Researchers in recombinant protein production have proposed miRNAs as biomarkers and cell engineering targets. However, miRNA expression remains understudied in Chinese Hamster Ovary cells, one of the most commonly used host cell systems for therapeutic protein production. To profile highly conserved miRNA expression, we used the miRCURY- miRNA array for screening miRNAs in CHO cells. The selection criteria for further miRNA profiling included positive hybridization signals and experimentally validated predicted regulatory targets. On the basis of screening, we selected 16 miRNAs for quantitative RT-PCR profiling. We profiled miR expression in parental CHO DG44 and CHO K1 cell lines as well as four recombinant DG44...
Cell death in general can be a physiological process of cell number regulation in tissue, or it can be the result of exo or endogenous injuries, such a low-dose of radiation. Chicken B cell population in the bursa of Fabricius are very susceptible to PCD. Our present studies concern the development of radiation damage of chicken defence mechanisms. In 6 experiments pathogen free chicken were irradiated by gamma rays with the total doses of 0.25, 0.5, 1.0, 2.0 and 4.0 Gy. The induction of apoptosis was checked by Flow-cyto-meter 12 h after irradiation in bursa cell suspension. There is some increase in the number of induced apoptotic cells 12 h after irradiation at the dose 0.5-.4.0 Gy. There were no significant changes in the proportion of proliferating lymphocytes (G2 M), but cellularity decreased significantly at dose 2.0 and 4.0 Gy/12 h after irradiation. ...
The expression of three c-onc genes (c-erb, c-myc, c-myb) was investigated in five cell lines established from fibrosarcomas induced with 20-methylcholanthrene (MCA) of Japanese quails. These cell lines showed low levels of the three c-onc genes, with the exception of two cell lines that accumulated moderate (MCAQ 1-4) and large amounts (MCAQ 3-5) of c-myc RNA. Molecular cloning and restriction endonuclease analyses indicated that expression of c-myc in these two cell lines were not associated with detectable rearrangements in the c-myc locus, that the size of the c-myc transcript (2.7 kb) in MCAQ 3-5 was similar to that of the normal c-myc messenger RNAs (mRNA) and that the transcriptional activatin observed in MCAQ 3-5 was not mediated by the LTR (long terminal repeat) of a proximate ALV (avian leukosis virus) provirus. Finally, when analyzed with the restriction enzymes Msp I and Hpa II, the c-myc ...
Shell Oil's exploration of profitable business opportunities afforded by fuel cells and by the emergence of a viable hydrogen economy is discussed. The emphasis in this paper is on the transportation sector, particularly the importance of a refueling infrastructure and the influence that consumer attitudes will have on which technological solution will gain the upper hand in hydrogen-powered vehicle development. Key issues facing the oil industry with regard to development of hydrogen as the new energy carrier are also reviewed. Methanol reformer fuel cell cars are the most likely to gain acceptability in the short term, but the probability of methanol fuel cell vehicles being replaced by gasoline or hydrogen fuelled fuel cell vehicles or be superseded by advances in internal combustion engine and after-treatment technology, are very real. Government regulations, fiscal incentives ...
Microorganisms are ubiquitous in subsurface environments although their populations sizes and metabolic activities can vary considerably depending on energy and nutrient inputs. As a result of their metabolic activities and the chemical properties of their cell surfaces and the exopolymers they produce, microorganisms can directly or indirectly facilitate the biotransformation of radionuclides, thus altering their solubility and overall fate and transport in the environment. Although biosorption to cell surfaces and exopolymers can be an important factor modifying the solubility of some radionuclides under specific conditions, oxidation state is often considered the single most important factor controlling their speciation and, therefore, environmental behavior.
Influenza virus infection during pregnancy has been implicated as one of cause of premature delivery, abortion and stillbirth. We have reported that cultured human fetal membrane chorion cells undergoing apoptosis by influenza virus infection secrete unidentified heat-stable monocyte differentiation-inducing (MDI) factors. In this study, cellular, biological and immunochemical characteristics of MDI factors were investigated using human monocytic leukemia THP-1 cells by nitroblue tetrazolium reduction and cell adhesion assays. The treatment of THP-1 cells with culture supernatants from the influenza virus-infected chorion cells induced the nitroblue tetrazolium reduction ability, which was inhibited by the addition of superoxide dismutase and diphenyleneiodonium chloride, an inhibitor for reduced nicotinamide adenine dinucleotide phosphate ...
Metabolic engineering of photosynthetic organisms is required for utilization of light energy and for reducing carbon emissions.Control of transcriptional regulators is a powerful approach for changing cellular dynamics, because a set of genes is concomitantly regulated. Here, we show that overexpression of a group 2 ? factor, SigE, enhances the expressions of sugar catabolic genes in the unicellular cyanobacterium, Synechocystis sp. PCC 6803. Transcriptome analysis revealed that genes for the oxidative pentose phosphate pathway and glycogen catabolism are induced by overproduction of SigE. Immunoblotting showed that protein levels of sugar catabolic enzymes, such as glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, glycogen phosphorylase, and isoamylase, are increased. Glycogen levels are reduced in the SigE-overexpressing strain grown under light. Metabolome analysis revealed that metabolite levels of ...
DNA methylation is considered as a potential cause of aberrations in regulation of gene expression during carcinogenesis. Therefore, changes in DNA methylation patterns may be targets for chemoprevention. In the present study, we investigated effects of all-trans retinoic acid (ATRA), vitamin D3, and resveratrol alone and in combination with adenosine analogues: 2-chloro-2'-deoxyadenosine (2CdA) and 9-beta-d-arabinosyl-2-fluoroadenine (F-ara-A), on methylation and expression of retinoic acid receptor beta 2 (RARbeta2) in MCF-7 and MDA-MB-231 breast cancer cell lines. Alterations in methylation and expression levels after treatment of cells with the tested compounds were evaluated by methylation-sensitive restriction analysis (MSRA) and real-time PCR, respectively. RARbeta2 promoter in the ...
Tissue-engineered heart valves are prone to early structural deterioration. We hypothesize that cell?scaffold interaction and mechanical deformation results in upregulation of genes related to osteogenic/chondrogenic differentiation and thus changes extracellular matrix (ECM) composition in human bone marrow mesenchymal stem cell (hBMSC)-derived tissue-engineered grafts. hBMSC were expanded and seeded onto poly-glycolic acid/poly-lactic acid scaffold for 14 days. Seeded tissue-engineered constructs (TEC) were subjected to cyclic flexure for 24?h, whereas control TEC was maintained in roller bottles for the same duration. hBMSC, TEC, and mechanically deformed TEC were subjected to gene-array and histological analysis. Expression levels of RNA and/or protein markers related to chondrogenesis...
TP63, a member of the TP53 gene family, is a nuclear marker of myoepithelial cells. Antibody against p63 is frequently used to aid in the diagnosis of prostate carcinoma, as well as in the identification of myoepithelial cells in other tissues including the breast. p63 is also a marker for squamous cell carcinoma. Recently, it was found that all p53 family members are involved in regulating the process of muscle differentiation through the retinoblastoma (RB) protein. Ablation of these p53 family functions blocks the differentiation program and promotes malignant transformation by enabling cooperating oncogenes to transform myoblasts. We therefore studied p63 expression in a number of neoplasms with myogenic differentiation. Immunohistochemical staining for p63 was performed on paraffin se...
Thymic epithelial cells (TECs) constitute a major component of the thymic stroma which provides a microenvironment critical for developing thymocytes. We have previously demonstrated that doxycycline (Dox), a tetracycline derivative, enhances the proliferation of the mouse thymic epithelial cell line 1 (MTEC1) via MAPK/ERK signal pathway. Herein we provide evidence that Dox also has profound impact on the cytokine production by MTEC1. Specifically, the expression of IL-6 and GM-CSF, both at mRNA and protein levels, was found to be increased in a time- and dose-dependent manner with the addition of Dox. Western blotting analysis revealed that treatment with Dox-induced phosphorylation of the p65 subunit of NF-kB and ERK. Notably, Dox-induced up-regulation of IL-6 and GM-CSF was largely abol...
Colon cancer is one of the leading causes of death and a major public health problem in western countries. We examined the isoflavone content of 70% ethanol extract of soy germ (SG) and its apoptotic effect in HT-29 colon cancer cells. Our results showed that the major isoflavones of the SG extract were daidzein and genistein, and it effectively induced apoptosis in HT-29 cancer cells. In addition, nuclear factor-kappa B (NF-kB) expression was reduced in cells treated with the SG extract, which reduced cyclooxygenase-2 (COX-2) and nitric oxide synthase (iNOS) expression. These combined effects ultimately resulted in apoptosis via caspase-3 activation. In addition, daidzein and genistein, the major isoflavones of SG extract, also exerted the apoptotic effect against HT-29 cancer cells. Thes...
In several vertebrate classes, the M?ller glia are capable of de-differentiating, proliferating, and acquiring a progenitor-like state in response to acute retinal injury or in response to exogenous growth factors. Our previous study has shown that M?ller cells can be activated and de-differentiated into retinal progenitors during Royal College of Surgeons (RCS) rats' degeneration, although the limited proliferation cannot maintain retinal function. We now report that rat retinal stem cells (rSCs) transplanted into RCS rats slowed the progression of retinal morphological degeneration and prevented the functional disruption. Further, we found that retinal progenitor cells labeled with Chx10 were increased significantly after rSCs transplantation, and most of them are mainly from activated M...
Oestrogen has been reported to modulate tumour necrosis factor (TNF), interleukin (IL)-1 and IL-6 cytokine levels in human mononuclear cell cultures. In the present study, the effects of exogenous oestrogen...Full Text Available
Although trefoil factor 1 (TFF1; previously named pS2) is abnormally expressed in about 50% of human breast tumors, its physiopathological role in this disease has been poorly studied. Moreover,...Full Text Available
Purpose.To report the increased production of extracellular transforming growth factor β-induced protein (TGFBIp) by human corneal epithelial cells (HCECs) after induction...Full Text Available
The conductivity of the membrane is a limiting factor for the efficiency and power density of PEFCs. Because this conductivity is strongly dependent on the membrane hydration, water management is an important aspect of PEFC optimisation. Single cell model experiments were made in order to determine the in-plane hydration of a Nafion{sup R} membrane under fuel cell conditions as function of the gas humidities. (author) 4 fig., 3 refs.
As the last step of urinary acidification, the inner medullary collecting duct (IMCD) is thought to secrete protons into the tubular lumens by means of a H(+)-translocating adenosinetriphosphatase (H(+)-ATPase). However, recent studies have also shown the existence of Na(+)-H+ exchange activity in IMCD cells. Although the physiological function of the antiporter in IMCD cells is unknown, activation of Na(+)-H+ exchange in other cell-culture systems has been suggested to be closely associated with the process of cell growth. Thus presence of Na(+)-H+ exchange may relate to the growth phase of these cells. To examine intracellular pH (pHi) regulation in growing IMCD cells, we studied proton transport by Na(+)-dependent and Na(+)-independent mechanisms by microfluorimetry using the pHi-sensitive dye ...
The loss of #alpha#-globin gene transcriptional activity rarely occurs as an acquired abnormality during the evolution of myeloproliferative disease or preleukemia. To test whether the mutation responsible for the loss of #alpha#-globin gene expression (hemoglobin H disease) in these patients is linked with the #alpha#-globin genes on chromosome 16, the authors transferred chromosome 16 from preleukemic patients with acquired hemoglobin H disease to mouse erythroleukemia cells and measured the transcriptional activity of the human #alpha#-globin genes. After transfer to mouse erythroleukemia cells, the expression of human #alpha#-globin genes from the peripheral blood or marrow cells of preleukemic patients with acquired hemoglobin H disease was similar to that of human #alpha#-globin genes transferred to mouse erythroleukemia cells from normal donors. These data showed that ...
The maintenance of a balance between cell gain and cell loss is essential for proper liver function. The exact role of aryl hydrocarbon receptor (AhR) in regulatingcell proliferation and apoptosis of liver cells remains unclear, since ligand-dependent activation of AhR has been shown to induce cell cycle arrest, proliferation, differentiation or apoptosis, depending on the cellular model used. AhR can directly interact with retinoblastoma protein in hepatic cells, forming protein complexes that can efficiently block cell cycle progression by inducing G1 arrest, or to induce the expression of inhibitors of cyclin-dependent kinases, such as p271. On the other hand, it has been suggested that AhR could play a stimulatory role in cell proliferation, either directly or by mediating a release from contact ...
A process has been developed that exploits the characteristics of microwave heating for the vitrification of high-level radioactive liquid waste. This process, microwave vitrification, has been successfully operated at pilot plant scale in an active cell using simulated liquid waste containing several curies of radioactivity. Excellent decontamination factors have been achieved for both volatiles and nonvolatiles with an average ruthenium decontamination factor of 490 and a gross alpha emitter decontamination factor of 100,000. Almost all the radioactivity is incorporated in a glass block.
A process has been developed that exploits the characteristics of microwave heating for the vitrification of high-level radioactive liquid waste. This process, microwave vitrification, has been successfully operated at pilot plant scale in an active cell using simulated liquid waste containing several curies of radioactivity. Excellent decontamination factors have been achieved for both volatiles and nonvolatiles with an average ruthenium decontamination factor of 490 and a gross alpha emitter decontamination factor of 100,000. Almost all the radioactivity is incorporated in a glass block.
pT181 is a naturally-occurring 4437 basepair (bp) plasmid isolated from Staphylococcus aureus which encodes inducible resistance to tetracycline (Tc). The DNA sequence data has identified three open reading frames (ORFs). The largest ORF B, has been found to be responsible for the Tc resistance phenotype of pT181. Since most Tc resistance systems appear to be regulated by an effector protein and a repressor protein, several Bal 31 deletion mutants of pT181 were constructed and analyzed in an effort to identify the elements involved in Tc resistance. Two transcomplementing groups of mutants were identified within the tet gene. The mechanism of Tc resistance was studied by assaying the accumulation of (7-/sup 3/H) Tc by Tc sensitive cells, and uninduced and induced pT181-containing cells. A sharp decrease in accumulation of the drug after an initial increase was observed in Tc induced pT181-containing ...
The expression of motor activity levels in response to novel situations is under complex genetic and environmental control. Several genetic loci have been implicated in the regulation of this behavioral phenotype, but their relationship to epigenetic and epistatic interactions is relatively unknown. Here, we report on a quantitative trait locus (QTL) on mouse chromosome 1 for novelty-induced motor activity in the open field, using chromosome substitution strains derived from a high active host strain (C57BL/6J) and a low active donor strain (A/J). The QTL for open field (horizontal distance moved) peaked at the location of Kcnj9, however, QTL detection was initially masked by an interplay of both grandparent genetic origin and genetic co-factors influencing behavior on chromosome 1. Our fi...
When the transmission line is very long or the generator is operated at a power factor nearly equal to 1.0, the machine regulated by an automatic voltage regulator (AVR) cannot be operated stably due to poor dynamic stability. To overcome this difficulty, the so called power system stabilizer (PSS) is very useful, in that output power or rotor speed of the generator is used as a feedback signal. The primary obective of the PSS is to damp the swing of the generator as quickly as possible. A method is proposed for designing PSS which yields a given eigenvalue. In the second method, the use of a Heffron-Phillips model is discussed. Next, a detailed procedure for the proposed design method is presented. A generalized method of a PSS design based on Park's equation and matrix operation is proposed.
Short synthetic single-stranded oligodeoxyribonucleotides (ssODNs) can be used to introduce subtle modifications into the genome of mouse embryonic stem cells (ESCs). We have previously shown that effective application of ssODN-mediated gene targeting in ESC requires (transient) suppression of DNA mismatch repair (MMR). However, whereas transient down-regulation of the mismatch recognition protein MSH2 allowed substitution of 3 or 4 nucleotides, 1 or 2 nucleotide substitutions were still suppressed. We now demonstrate that single- or dinucleotide substitution can effectively be achieved by transient down-regulation of the downstream MMR protein MLH1. By exploiting highly specific real-time PCR, we demonstrate the feasibility of substituting a single basepair in a non-selectable gene. Howev...
...comAbstract: Hepatocellular carcinoma (HCC), once thought to be a rare tumor in North America, is a rapidly increasing type of cancer in recent years in the United States. Current treatment modalities to halt the disease progression are only marginally effective. The mainstay treatment ...In addition, NM was shown to down-regulate urokinase plasminogen activator (by fibrin zymography) and up-regulate tissue inhibitors of metalloproteinases (by reverse zymography) in another HCC cell line, Sk-Hep-1. MMP-2 and MMP-9 activities were further modulated by cytokines, inducers and inhibitors, including NM. In ... Our results suggest that NM is an excellent candidate for therapeutic use in the treatment HCC by inhibiting critical parameters in cancer development and progression, such as proliferation, invasion and metastasis, and by inducing apoptosis. Last update: 2 September 2011 JavaScript seems ...
Isolation and expansion of neural stem cells (NSCs) of human origin are crucial for successful development of cell therapy approaches in neurodegenerative diseases. Different epigenetic and genetic immortalization strategies have been established for long-term maintenance and expansion of these cells in vitro. Here we report the generation of a new, clonal NSC (hc-NSC) line, derived from human fetal cortical tissue, based on v-myc immortalization. Using immunocytochemistry, we show that these cells retain the characteristics of NSCs after more than 50 passages. Under proliferation conditions, when supplemented with epidermal and basic fibroblast growth factors, the hc-NSCs expressed neural stem/progenitor cell markers like nestin, vimentin and Sox2. When growth factors were withdrawn, proliferation and expression of v-myc and telomerase were ...
Aim To better define the indications for adrenalectomy for adrenal metastasis we have analysed factors predicting survival in our institutional series. Methods A consecutive series of 30 patients undergoing adrenalectomy for metastasis (1996-2007), excluding patients with simultaneous ipsilateral renal cell carcinoma (RCC), was studied. Metastases were regarded as synchronous (6 mo), depending on the interval after primary surgery. Survival was calculated from time of adrenalectomy and factors influencing survival were identified. Results The tumour diagnoses were RCC n = 9, malignant melanoma n = 5, non-small-cell lung cancer n = 5, colorectal carcinoma n = 4, foregut carcinoid n = 2, adrenocortical carcinoma, breast cancer, hepatocellular carcinoma, urothelial c...
Keratinocyte growth factor receptor (KGFR) and fibroblast growth factor receptor (FGFR) 2c share identical amino acid sequences, except for a 46-amino acid domain in the extracellular region. Monoclonal antibodies (MAbs) specific to KGFR have not been reported nor are commercially available. In this study, we generated murine MAbs specific to KGFR in non-obese diabetic (NOD) mice using a modified Repeated Immunizations at Multiple Sites (RIMMS) technology. Stable cell lines expressing the full-length human KGFR or FGFR2c were produced to facilitate the identification of KGFR-specific MAbs. Following the initial screening of hybridoma clones with a fluorescence-based, confocal cell detection method and ELISA, KGFR-specific MAbs were selected and confirmed by flow cytometry and Western blot ...
We previously reported that puromycin-insensitive leucyl-specific aminopeptidase (PILSAP) is required for vascular endothelial growth factor (VEGF)- and basic fibroblast growth factor (bFGF)-induced angiogenesis and for endothelial differentiation from embryonic stem (ES) cells via the aminopeptidase activity of PILSAP. In this study, we searched for molecules that function during angiogenesis with PILSAP. We performed proteome analysis of nuclear extracts from embryoid bodies (EBs) made from ES cells transfected with mutant PILSAP lacking aminopeptidase activity and mock EBs. We identified pigpen, a 67-kDa nuclear coiled body component protein. Immunoprecipitation and western blotting demonstrated the binding of PILSAP and pigpen in endothelial cells (ECs), and this interaction was enhanc...
Calcium (Ca) plays an important role in regulating various cellular processes. In a variety of cell types, Ca signaling occurs within microdomains where channels deliver localized pulses of Ca which activate a nearby collection of Ca-sensitive receptors. The small number of channels involved ensures that the signaling process is stochastic. The aggregate response of several thousand of these microdomains yields a whole-cell response which dictates the cell behavior. Here, we study analytically the statistical properties of a population of these microdomains in response to a trigger signal. We apply these results to understand the relationship between Ca influx and Ca release in cardiac cells. In this context, we use a first passage time approach to show analytically how Ca release in the whole cell depends on the single channel kinetics of Ca channels and the ...
The endothelin-B (ETB) receptor is a G-protein-coupled receptor that binds endothelin ligands and is essential for the development of epidermal melanocytes and enteric neurons. Recent reports indicate that ETB is localized to nuclei in cardiac ventricular myocytes, although it has been thought that ETB is localized mainly on the plasma membrane. It remains unknown, however, whether this unique distribution of ETB occurs in other tissues. To elucidate the subcellular distribution of ETB in the intestine, we performed immunofluorescence of ETB in mouse intestine using a specific antibody. ETB-like immunoreactivity was detected in both the mucosal and muscle layers. In the mucosal layer, villous epithelial cells, stromal cells of the lamina propria, and cryptic cells were immunostained. Subcellularly, ETB is localized mainly to the nuclei of villous epithelial cells. In the muscle layer, immunoreactivity ...
Using a syngeneic p53-null mouse mammary gland tumor model that closely mimics human breast cancer, we have identified, by limiting dilution transplantation and in vitro mammosphere assay, a Lin(-)CD29(H)CD24(H) subpopulation of tumor-initiating cells. Upon subsequent transplantation, this subpopulation generated heterogeneous tumors that displayed properties similar to the primary tumor. Analysis of biomarkers suggests the Lin(-)CD29(H)CD24(H) subpopulation may have arisen from a bipotent mammary progenitor. Differentially expressed genes in the Lin(-)CD29(H)CD24(H) mouse mammary gland tumor-initiating cell population include those involved in DNA damage response and repair, as well as genes involved in epigenetic regulation previously shown to be critical for stem cell self-renewal. These studies provide in vitro and in vivo data that support the cancer stem cell (CSC) hypothesis. ...
Many assays for oncogenic transformation have been developed ranging from those in established rodent cell lines where morphological alteration is scored, to those in human cells growing in nude mice where tumor invasiveness is scored. In general, systems that are most quantitaive are also the least relevant in terms of human carcinogenesis and human risk estimation. The development of cell culture systems has made it possible to assess at the cellular level the oncogenic potential of a variety of chemical, physical and viral agents. Cell culture systems afford the opportunity to identify factors and conditions that may prevent or enhance cellular transformation by radiation and chemicals. Permissive and protective factors in radiation-induced transformation include thyroid hormone and the tumor promoter TPA that increase the transformation incidence for a given ...
Many assays for oncogenic transformation have been developed ranging from those in established rodent cell lines where morphological alteration is scored, to those in human cells growing in nude mice where tumor invasiveness is scored. In general, systems that are most quantitaive are also the least relevant in terms of human carcinogenesis and human risk estimation. The development of cell culture systems has made it possible to assess at the cellular level the oncogenic potential of a variety of chemical, physical and viral agents. Cell culture systems afford the opportunity to identify factors and conditions that may prevent or enhance cellular transformation by radiation and chemicals. Permissive and protective factors in radiation-induced transformation include thyroid hormone and the tumor promoter TPA that increase the transformation incidence for a given ...
Glycyrrhiza glabra root is one of the common traditional Chinese medicines and used as flavoring and sweetening agents for tobaccos, chewing gums, candies, toothpaste and beverages. While glycyrrhizin is one of the main components in the extract of G. glabra root and has been characterized, the other components have not been well characterized. The mechanism of growth activation of breast cancer MCF-7 cells, including the activation of Erk1/2 and Akt, and the transcriptional regulation of estrogen-responsive genes, was examined by means of sulforhodamine B, luciferase reporter gene, real-time RT-PCR and Western blotting assays after the induction of the cells with the extract of G. glabra root. The extract has similar activity to that induced by 17beta-estradiol (E(2)), although glycyrrhizin did not show such an activity. Moreover, the estrogen receptor alpha-dependent neurite outgrowth induced by the extract was similar to ...
The herpes simplex virus type 1 thymidine kinase (HSV1-TK) reporter system is being used to directly and indirectly monitor therapeutic gene expression, immune cell trafficking and protein-protein interactions in various living animals. However, the issues of HSV1-TK enzyme stability in living cells and whether this reporter system is optimal for dynamic studies of gene expression events in genetic imaging have not be addressed. The purpose of the present study was to evaluate the application of this reporter system in dynamic studies of transcriptional gene regulation. To achieve this purpose, we established two tetracycline-inducible murine sarcoma cell lines, tetracycline-turn-off HSV1-tk-expressing cell line (NG4TL4/tet-off-HSV1-tk) and tetracycline-turn-off Luc-expressing cell line (NG4TL4/tet-off-Luc), to create an artificially ...
The purpose of the project is to further develop a Danish natural gas reformer system including optimisation of subsystems and the overall system consisting of a natural gas reformer and fuel cell CHP generator. This will contribute to the evaluation of to what extend Denmark shall develop small reformer units for PEM fuel Cells. In the project a reformer system with a high degree of automatic control has been build that fulfils the CHP requirements to operation time, dynamics etc. This work, with a FP05 reformer unit, has given valuable results concerning the possibilities and limitations of the reformer technology for CHP usage. It is important that the reformer and fuel cell units are designed with matching yields to optimise efficiency, turn-down start-up time etc. The burner that delivers heat for the steam reaction shall be able to use natural gas as fuel. This gives the possibility of using existing burner ...
The paper evaluates standardization of regulations on safety of electrical equipment for underground coal mines in the USSR. Factors increasing hazards of electrical failures of equipment in underground coal mines are analyzed: reduced lighting, increased humidity and dusts, damage caused by falling rocks or damage during haulage in underground workings, installation of electrical equipment in places easily accessible to untrained personnel. Standards on safety of electrical equipment for underground coal mining valid in the USSR are reviewed: the PIRNEh regulations on production of electrical equipment for coal mines developed by the VNIIVEh Institute, and the GOST national standards. International cooperation within the COMECON on safety of mining electrical equipment (the Interelectro Committee of the COMECON) is described. Certification of electrical equipment for coal mines is discussed on the example of electrical ...
The product of the human GRO gene is a cytokine with inflammatory and growth-regulatory properties; GRO is also called MGSA for melanoma growth-stimulatory activity. The authors have identified two additional genes, GRO#beta# and GRO#gamma#, that share 90% and 86% identity at the deduced amino acid level with the original GRO#alpha# isolate. One amino acid substitution of proline in GRO#alpha# by leucine in GRO#beta# and GRO#gamma# leads to a large predicted change in protein conformation. Significant differences also exist in the 3' untranslated region, including different numbers of ATTTA repeats associated with mRNA instability. A 122-base-pair region in the 3' region is conserved among the three GRO genes, and a part of it is also conserved in the Chinese hamster genome, suggesting a role in regulation. DNA hybridization with oligonucleotide probes and partial sequence analysis of the genomic clones confirm that the three forms are derived from related but ...
A comparison of the loss mechanisms in screen-printed solar cells relative to buried contact cells and cells with photolithography-defined contacts is presented in this paper. Model calculations show that emitter recombination accounts for about 0.5% absolute efficiency loss in conventional screen-printed cells with low-sheet-resistance emitters. Ohmic contact to high-sheet-resistance emitters by screen-printing has been investigated to regain this efficiency loss. Our work shows that good quality ohmic contacts to high sheet-resistance emitters can be achieved if the glass frit chemistry and Ag particle size are carefully tailored. The melting characteristics of the glass frit determine the firing scheme suitable for low contact resistance and high fill factors. In addition, small to regular Ag particles were found to help achieve a higher open-circuit voltage and maintain a low ...
Under drought conditions, sucrose distribution (osmotic adjustment vs. export) may be regulated at the mesophyll plasmalemma/tonoplast. Leaves were given {sup 14}CO{sub 2} for a 30/30 min pulse/chase. Peeled leaf discs were put in low or high osmotic solutions to monitor release of labeled solutes. High turgor increased efflux rates double those at low turgor. About 30% and 55% of the released label was in the sugar (sucrose + hexose) fractions at low and high turgor, respectively. Response to changes in cell turgor was rapid and reversible. PCMBS had no effect on efflux. NEM and CCCP enhanced efflux at high turgor. Presence of unlabeled sucrose in the wash solutions greatly enhanced sucrose efflux in a turgor-dependent manner; suggesting the presence of a sucrose exchange system, which appeared to be at the tonoplast. Turgor-regulated efflux involved both the tonoplast and plasmalemma. However, efflux across the ...
A competitive repopulation assay utilizing chromosome markers was used to assay the reconstituting potential of hematopoietic populations. The test populations consisted of tibial murine marrow locally irradiated with doses ranging from 1.5 Gy to 8.5 Gy and of marrow generated from either murine splenic or marrow stem cells. The purpose of this assay was to assess the innate proliferative potential and microenvironmental influences on the ability to repopulate. Regardless of origin, spleen repopulating ability consistently agreed with spleen colony-forming unit (CFU-s) content. Doses of radiation from 5 Gy to 8.5 Gy diminished, by a factor of 2, the ability to repopulate marrow despite maintenance of CFU-s levels. Marrow generated from splenic stem cells had one-fifth the repopulating ability of marrow derived from marrow stem cells, even though CFU-s levels were equivalent. The results imply that the ...
In recent years it has become evident from epidemiological and experimental data that a large number of environmental factors, including diet, play a role in modifying the incidence of cancer. Cell culture systems in which oncogenic transformation serves as an end point are powerful tools for evaluating these questions. Using such systems it has been shown recently that pyrolysis products from charred surfaces of broiled meat and fish can transform hamster embryo cells in vitro as well as produce tumors in the animal. Our studies in vitro have demonstrated the oncogenic potential of ionizing radiation in both hamster and human cells and have established in hamster cells the dose response relationship at doses ranging from 1 to 600 rad for x-rays and 0.1 to 150 rad for neutrons. The present work was aimed at evaluating whether there exists a cocarcinogenic interaction between a ...
Mammary glands are special tissue characterized by proliferation of the epithelium, during puberty and pregnancy and by programmed cell death, during involution. In this study, apoptosis was identified by TUNEL staining and then related to cell proliferation, as determined by Ki-67 staining. The apoptotic index was at its highest at 8 days of involution, whereas the proliferation index was at its highest during lactation. Caspase-3 was immunolocalised only in mast cells and along the basal membrane in the mammary tissue at -10 days from lambing, 150 days of lactation and at 8 days of involution. This finding could indicate that caspase-3 is not involved in sheep mammary gland apoptosis, but that other proteins - such as apoptosis inducing factor (AIF) - can trigger apoptosis, through the m...
This report is a summary of the contribution of nitrogen and phosphorus in the eutrophication process of inland and coastal waters. Special attention was paid to the mechanisms of these nutrients in regulating biological processes and to the methods available in estimating their effects in the eutrophication of water bodies. The report includes five chapters which are entitled: Introduction, which is a general background to the subject with special attention to the requirements of the Finnish Water Act. Phosphorus and nitrogen as factorsregulating biological processes. The topics included are: definition of eutrophication, forms of phosphorus and nitrogen and their sources to inland and coastal waters, effects of these nutrients as growth factors of phytoplankton and macrophytes and consequences of eutrophication. Estimation of the effects of phosphorus and nitrogen. The topics discussed from the point ...
Radiation protection programs for workers are based, in the United States, on a hierarchy of limitations stemming from Federal guidance approved by the President. This guidance, which consists of principles, policies, and numerical primary guides, is used by Federal agencies as the basis for developing and implementing their own regulatory standards. The primary guides are usually expressed in terms of limiting doses to workers. The protection of workers against taking radioactive materials into the body, however, is accomplished largely through the use of regulations based on derived guides expressed in terms of quantities or concentrations of radionuclides. The values of these derived guides are chosen so as to assure that workers in work environments that conform to them are unlikely to receive radiation doses that exceed the primary guides. The purpose of the present report is to set forth derived guides that are consistent with current Federal radiation ...
The GTPases comprise a protein superfamily of highly conserved molecular switches adapted to many diverse functions. These proteins are found in all domains of life and often perform essential roles in fundamental cellular processes. Analysis of data from genome sequencing projects demonstrates that bacteria possess a core of 11 universally conserved GTPases (elongation factor G and Tu, initiation factor 2, LepA, Era, Obg, ThdF/TrmE, Ffh, FtsY, EngA and YchF). Investigations aimed at understanding the function of GTPases indicate that a second conserved feature of these proteins is that they elicit their function through interaction with RNA and/or ribosomes. An emerging concept suggests that the 11 universal GTPases are either necessary for ribosome function or transmitting information from the ribosome to downstream targets for the purpose of generating specific cellular responses. Furthermore, it is suggested that progenitor GTPases were ...
Although the p53 tumor suppressor is relatively well characterized, much less is known about the functions of other members of the p53 family, p73 and p63. Here, we present evidence that in specific pathological conditions caused by exposure of normal cells to bile acids in acidic conditions, p73 protein plays the predominant role in the DNA damage response. These pathological conditions frequently occur during gastric reflux in the human esophagus and are associated with progression to esophageal adenocarcinoma. We found that despite strong DNA damage induced by bile acid exposure, only p73 (but not p53 and p63) is selectively activated in a c-Abl kinase-dependent manner. The activated p73 protein induces DNA damage repair. Using a human DNA repair PCR array, we identified multiple DNA repair genes affected by p73. Two glycosylases involved in base excision repair, SMUG1 and MUTYH, were characterized and found to be transcriptionally regulated ...
The epidermal compartment is complex and organized into several strata composed of keratinocytes (KCs), including basal, spinous, granular, and cornified layers. The continuous process of self-renewal and barrier formation is dependent on a homeostatic balance achieved amongst KCs involving proliferation, differentiation, and cell death. To determine genes responsible for initiating and maintaining a cornified epidermis, organotypic cultures comprised entirely of stratified KCs creating epidermal equivalents (EE) were raised from a submerged state to an air/liquid (A/L) interface. Compared to the array profile of submerged cultures containing KCs predominantly in a proliferative (relatively undifferentiated) state, EEs raised to an A/L interface displayed a remarkably consistent and distinct profile of mRNAs. Cultures lifted to an A/L interface triggered the induction of gene groups that regulate proliferation, differentiation, and ...
This study describes the role of "inflammatory" oxidized (Ox) phospholipids in regulation of rahU (PA0122) expression and biofilm formation in Pseudomonas aeruginosa (383) wild type (rahU+) and rahU mutant (rahU-) strains. Functional analysis of RahU protein from P. aeruginosa in presence of Ox-phospholipids show: (a) LysoPC modulates RahU gene/and protein expression in rahU+ cells; (b) rahU promoter activity is increased by lysoPC and inhibited by PAPC, Ox-PAPC and arachidonic acid; the latter inhibitory effect can be reversed by lysoPC, which was enzymatically derived from PAPC; (c) biofilm formation increased in rahU- cells as compared to rahU+; and (d) inhibition of rahU promoter activity by PAPC and AA (but not lysoPC) showed significantly augmented biofilm formation in rahU+ but not ...
Environmental arsenic is a world-wide health issue, making it imperative for us to understand mechanisms of metalloid uptake and detoxification. The predominant intracellular form is the highly mephitic arsenite, which is detoxified by removal from cytosol. What prevents arsenite toxicity as it diffuses through cytosol to efflux systems? Although intracellular copper is regulated by metallochaperones, no chaperones involved in conferring resistance to other metals have been identified. In this article, we report identification of an arsenic chaperone, ArsD, encoded by the arsRDABC operon of Escherichia coli. ArsD transfers trivalent metalloids to ArsA, the catalytic subunit of an As(III)/Sb(III) efflux pump. Interaction with ArsD increases the affinity of ArsA for arsenite, thus increasing its ATPase activity at lower concentrations of arsenite and enhancing the rate of arsenite extrusion. Cells are consequently resistant to environmental ...
Discusses Czechoslovak regulations for determining moisture content in brown coal. Standard formulae for determining total moisture content and residual water content are described. Factors that influence accuracy in determining moisture content under laboratory conditions are analyzed: brown coal type, season of the year, air humidity, method and duration of coal sample drying, number of coal samples simultaneously dried in 1 dryer, ash content of coal. On the basis of analysis recommendations for a modified method of determining moisture content in brown coal are made. 5 refs.
A reliable source of specific criteria for recognizing a wetland, as defined for regulatory purposes would be valuable. In 1987 the Army Corps of Engineers developed a technical manual for identifying wetlands (1987 Wetlands Manual). An interagency manual (1989 Wetlands Manual) was later developed. This manual has been used to identify wetlands according to three evidentiary factors: vegetation, hydrology, and soil. This paper addresses the development of criteria to delineate wetlands, and describes some of the logic used by federal courts to uphold the limited constitutional use of the 1989 Wetlands Manual.
With the increase of cross-Strait economic activity, the interaction between Taiwanese business people and the Chinese government has gradually changed. As Taiwanese investment grew in volume, so did the number and frequency of contacts between the parties; a more institutionalised form regulating these contacts was established as a result. Nowadays Taiwanese businessmen have become an identifiable factor in Chinese governmental policy implementation; the process also has far-reaching implications. This paper argues that Taiwanese capital has become a Chinese governmental security asset and examines the importance of this factor when discussing conventional government/business interaction. This paper concludes that a superior national interest guides the warm welcome given by the Chinese g...
Purpose To study the activation and expression of vascular (aorta and small mesenteric arteries) potassium channels during septic shock with or without modulation of the NO pathway. Methods Septic shock was induced in rats by peritonitis. Selective inhibitors of vascular KATP (PNU-37883A) or BKCa [iberiotoxin (IbTX)] channels were used to demonstrate their involvement in vascular hyporeactivity. Vascular response to phenylephrine was measured on aorta and small mesenteric arteries mounted on a wire myograph. Vascular expression of potassium channels was studied by PCR and Western blot, in the presence or absence of 1400W, an inducible NO synthase (iNOS) inhibitor. Aortic activation of the transcriptional factor nuclear factor-kappaB (NF-?B) was assessed by electrophoretic mobility shift as...
The paper presents some aspects relating to the importance of a good communication and cooperation between all factors involved in procurement process at Societatea Nationala 'Nuclearelectrica', SNN. In order to comply with the internal and international rules related to safety in nuclear field and public procurement requirements and for maintaining a high standard of operational performance of Cernavoda NPP, adequate procurement systems were developed by SNN SA. The importance of human factor and the training activities for all personnel from this chain of procurement process is the main key issue to maintain high quality of their activities considering that procurement documents are reviewed and approved before to be issued by all departments involved in procurement process. The specialized department for public acquisition is supervising that the procurement processes initiated at the level of branches, in accordance with their needs and ...
The cAMP response element-binding protein (CREB) is a highly conserved transcription factor that integrates signaling through the cAMP-dependent protein kinase A (PKA) in many eukaryotes. PKA plays a critical role in Dictyostelium development but no CREB homologue has been identified in this system. Here we show that Dictyostelium utilizes a CREB-like protein, BzpF, to integrate PKA signaling during late development. bzpF^- mutants produce compromised spores, which are extremely unstable and germination defective. Previously, we have found that BzpF binds the canonical CRE motif in vitro. In this paper, we determined the DNA binding specificity of BzpF using protein binding microarray (PBM) and showed that the motif with the highest specificity is a CRE-like sequence. BzpF is necessary to ...
Drosophila melanogaster has long been at the forefront of studies of transcriptional regulation in animals. Many fundamental ideas--such as cis control elements that act over long distances, the regulation of development by hierarchical cascades of transcription factors, dosage compensation, and position effect variegation--originated from studies of the fruit fly. The recent completion of the euchromatic DNA sequence of Drosophila is another breakthrough. The sequence data highlight important unanswered questions. For example, only one-fifth of the 124 Mb of Drosophila euchromatic DNA codes for protein. The function of the remaining 100 Mb of mostly unique DNA is largely unknown. Some proportion of this non-reading frame DNA must encode the functional recognition sites targeted by the approximately 700 sequence-specific DNA binding proteins that regulate transcription in Drosophila, but what ...
Tungsten, in the form of tungstate, polymerizes with phosphate, and as extensive polymerization occurs, cellular phosphorylation and dephosphorylation reactions may be disrupted, resulting in negative effects on cellular functions. A series of studies were conducted to evaluate the effect of tungsten on several phosphate-dependent intracellular functions, including energy cycling (ATP), regulation of enzyme activity (cytosolic protein tyrosine kinase [cytPTK] and tyrosine phosphatase), and intracellular secondary messengers (cyclic adenosine monophosphate [cAMP]). Rat noncancerous hepatocyte (Clone-9), rat cancerous hepatocyte (H4IIE), and human cancerous hepatocyte (HepG2) cells were exposed to 1-1000 mg/l tungsten (in the form of sodium tungstate) for 24 h, lysed, and analyzed for the ab...
Abstract The Hippo pathway is an evolutionally conserved protein kinase cascade involved in regulating organ size in vivo and cell contact inhibition in vitro by governing cell proliferation and apoptosis. Deregulation of the Hippo pathway is linked to cancer development. Its first core kinase Warts was identified in Drosophila more than 15 years ago, but it gained much attention when other core components of the pathway were identified 8 years later. Major discoveries of the pathway were made during past several years. The core kinase components Hippo, Salvador, Warts, and Mats in the fly and Mst1/2, WW45, Lats1/2, and Mob1 in mammals phosphorylate and inactivate downstream transcriptional co-activators Yorkie in the fly, Yes-associated protein (YAP) and transcriptional co-activator with ...
Amphiphysin is a protein concentrated in neuronal synapses and peripherally associated with neurotransmitter vesicles. It is expressed in many neurons of the central and peripheral nervous systems, in the adrenal medulla, in the anterior and posterior pituitary, in cell lines of the endocrine pancreas, and in spermatocytes. Its subcellular localization and tissue distribution indicate a potential involvement in mechanisms of regulated exocytosis. A role in the dynamic organization of the membrane-associated cytoskeleton is suggested by structural homology to the products of two yeast genes, RVS161 and RVS167, whose mutation results in an abnormal actin distribution, disturbs budding morphology, and impairs cell entry into stationary phase. Limited stretches of sequence similarity, including an SH3 domain, are also shared with other actin-binding proteins. Amphiphysin is the dominant autoantigen in paraneoplastic Stiff-Man ...
Morusin is a pure compound isolated from root bark of Morusaustralis (Moraceae). In this study, we demonstrated that morusin significantly inhibited the growth and clonogenicity of human colorectal cancer HT-29 cells. Apoptosis induced by morusin was characterized by accumulation of cells at the sub-G_1 phase, fragmentation of DNA, and condensation of chromatin. Morusin also inhibited the phosphorylation of IKK-#alpha#, IKK-#beta# and I#kappa#B-#alpha#, increased expression of I#kappa#B-#alpha#, and suppressed nuclear translocation of NF-#kappa#B and its DNA binding activity. Dephosphorylation of NF-#kappa#B upstream regulators PI3K, Akt and PDK1 was also displayed. In addition, activation of caspase-8, change of mitochondrial membrane potential, release of cytochrome c and Smac/DIABLO, and activation of caspase-9 and -3 were observed at the early time point. Downregulation in the expression of Ku70 and XIAP was exhibited ...
Genome-wide association studies have linked lung cancer risk with a region of chromosome 15q25.1 containing CHRNA3, CHRNA5 and CHRNB4 encoding a3, a5 and b4 subunits of nicotinic acetylcholine receptors (nAChR), respectively. One of the strongest associations was observed for a non-silent single-nucleotide polymorphism at codon 398 in CHRNA5. Here, we have used pharmacological (antagonists) or genetic (RNA interference) interventions to modulate the activity of CHRNA5 in non-transformed bronchial cells and in lung cancer cell lines. In both cell types, silencing CHRNA5 or inhibiting receptors containing nAChR a5 with a-conotoxin MII exerted a nicotine-like effect, with increased motility and invasiveness in vitro and increasing calcium influx. The effects on motility were enhanced by addit...
#gamma# spectroscopy methods have been applied to determine the effects of two freshwater benthic macroinvertebrates, on reworking of sediments and the transfer of solutes across the sediment-water interface. Natural lake sediments and overlying water were contained in temperature-regulated rectangular plastic cells. After addition of Stylodrilus (oligochaete worms) and Pontoporeia (crustacean amphipods) to these microcosms, the vertical distribution of Cs-137 (a tracer of particle transport) and Na-22 (a tracer of solute transport) were determined. In cells with Stylodrilus, the Cs-137 layer moved downward at a rate that decreased exponentially with time. In cells with Pontoporeia, Cs-137 activity was smeared downward in time owing to eddy diffusive mixing of sediments over a small range (1-2 cm). In cells without worms, the veneer of Cs active material remained at the interface ...
Prognosis of 95 consecutive patients with non-small cell lung cancer with brain metastases were evaluated. Three factors, therapy for brain metastases, general performance status (PS) and distant metastases to other organs had significant impact on survival. Among these 3 factors, PS was independent from the other 2 factors. Significant correlation was present, however, between therapy and other organ metastases, and few patients with brain and other distant metastases received aggressive treatment for brain metastases. Cranial irradiation had significant impact on survival even in those patients with brain and other distant metastases. Cranial irradiation also reduced death from brain metastases in responders. Our results indicate that there are several subgroups with different prognosis in patients with non-small cell lung cancer with brain metastases, therefore the most ...
The evolution of "humanized" (i.e., free of animal sourced reagents) and ultimately chemically defined culture systems for human embryo stem cell (hESC) isolation and culture is of importance to improving their efficacy and safety in research and therapeutic applications. This can be achieved by integration of a multitude of individual approaches to replace or eliminate specific animal sourced reagents into a single comprehensive protocol. In the present study our objective was to integrate strategies obviating reliance on some of the most poorly defined and path-critical factors associated with hESC derivation, namely the use of animal immune compliment to isolate embryo inner cell mass, and animal sourced serum products and feeder cells to sustain hESC growth and attachment. As a result we report the derivation of six new hESC lines isolated by outgrowth from whole blastocysts on an extracellular ...
Abstract in english The main objective of the research presented here is to relate anatomical features of wood species that affect the interactions between polymeric phases and performance of wood plastic composites (WPC). These interactions are related to the probable interlocking volume and surface area for stress transfer in a WPC. Composites were produced from different wood species and analyzed using SEM (scanning electron microscopy). Results showed that wood species with high interfac (more) ial areas may increase mechanical interlocking, reflected in the viscous constant of the Maxwell model. A complicating factor is that the relation of cell wall thickness-lumen diameter and the interconnectivity between wood cells in a wood, affect the potential for cell collapse. When wood cells collapse, the penetration of the thermoplastic into the wood structure is almost always ...
Since microwaves are used in human cancer therapy, information on specific biological effects of microwaves at elevated temperatures is important. To help supply this information, we exposed mammalian cells (CHO) and bacteria (Serratia marcescens) to hyperthermal temperatures (43, 44, and 45/sup o/C for CHO and 48, 49, and 50/sup o/C for the bacteria) with and without microwave irradiation. Temperature control was maintained by a refrigeration-reheat system and high-velocity water recirculation. The 2450-MHz microwave source was operated in a pulsed mode with power density up to 500 mW/cm/sup 2/. As expected, the survival curve slopes for both cell types increased rapidly with temperature, doubling for each degree Celsius. Microwave irradiation produced no significant change in extrapolation number for either cell type. However, survival curves of CHO cells which received microwaves were steeper by a ...
WR-2721 (S-2-(3-aminopropylamino)ethylphosphorothioic acid) has been demonstrated to be cytotoxic to stem spermatogonia in the mouse. Five and 10 injections of 300 mg/kg killed sufficient numbers of stem cells to reduce sperm production 56 days after treatment by 16 and 43%, respectively. Single injections of 300 or 400 mg/kg of WR-2721 given 15 min after irradiation produced negligible toxicity to stem cells as measured by counts of repopulated tubules; 600 mg/kg reduced stem cell survival by 47%. Four daily injections of 300 mg/kg given 4, 3, 2, and 1 days prior to irradiation reduced stem cell survival by about 60%. The cytotoxic effects of WR-2721 on testicular stem cells at least partially explains the reduced protection factors observed in the testis with low doses of radiation and during fractionated treatments involving multiple injections of drug.
Cholestatic liver injury induced by alpha-naphthylisothiocyanate (ANIT) is provoked by injury to intrahepatic bile ducts and the progression of hepatic necrosis requires the procoagulant protein tissue factor (TF) and extrahepatic cells including neutrophils. Recent studies have shown that myeloid cell TF contributes to neutrophil activation. We tested the hypothesis that myeloid cell TF contributes to neutrophil activation in ANIT-treated mice. TF activity in liver homogenates increased significantly in TF^f^l^o^x^/^f^l^o^x mice treated with ANIT, but not in TF^f^l^o^x^/^f^l^o^x/LysMCre mice (TFD^M^y^e^l^o^i^d mice), which have reduced TF expression in monocytes/macrophages and neutrophils. Myeloid cell-specific TF deficiency did not alter expression of the chemokines KC or MIP-2 but redu...
This paper presents a new grid connected inverter for fuel cells. It consists of a two stage power conversion topology. Since the fuel cell operates with a low voltage in a wide voltage range (25 V-45 V) this volt- age must be transformed to around 350-400 V in order to invert this dc power into ac power to the grid. The proposed converter consists of an isolated dc-dc converter cascaded with a single phase H-bridge inverter. The dc-dc converter is a current-fed push-pull converter. A new dedicated voltage mode startup procedure has been developed in order to limit the inrush current during startup. The inverter is controlled as a power factor controller with resistor emulation.Experimental results of converter efficiency, grid performance and fuel cell response are shown for a 1 kW prototype. The proposed converter exhibits a high efficiency in a wide power range (higher than 92%) and the inverter ...
Introduction The progressive growth of malignancies is accompanied by a decline in the immune response through mechanisms which are poorly understood. Apoptosis and induction of inflammation by tumor released cytokines as tumor escape mechanisms have been proposed to play an important role in colorectal carcinogenesis. Methods Expression of Tumor necrosis factor-alpha (TNF-?) was analyzed in colorectal cancer specimen and the cancer cell line HT-29 by immunohistochemistry and RT-PCR. TNF-? expression on protein and mRNA level were correlated with clinical characteristics and impact on survival. TNFR-1 was co-labelled with TNF-? and CD8+ cytotoxic T cells in immunofluorescence double staining experiments. Results: 94% (n?=?98/104) of the patients with CRC expressed TNF-?. High TNF-? express...
The stages of processes leading to radiation damage are studied, as well as, the direct and indirect mechanics of its production. The radiation effects on nucleic acid and protein macro moleculas are treated. The physical and chemical factors that modify radiosensibility are analysed, in particular the oxygen effects, the sensibilization by analogues of nitrogen bases, post-effects, chemical protection and inherent cellfactors. Consideration is given to restoration processes by excision of injured fragments, the bloching of the excision restoration processes, the restoration of lesions caused by ionizing radiations and to the restoration by genetic recombination. Referring to somatic effects of radiation, the early ones and the acute syndrome of radiation are discussed. The difference of radiosensibility observed in mammalian cells and main observable alterations in tissues and organs are commented. ...
Within the framework of the French inter lab SPACT project (Fuel Cell Systems for Transportation Applications), the behavior of a 5 kW PEM fuel cell stack, fed by humidified hydrogen and compressed air, is investigated in a test platform at Belfort, France. A set of polarization curves are recorded, under various conditions of stack temperature, gas pressure, and stoichiometry rates, in order to obtain a kind of cartography, representing the static stack performance. Initially, the tests are defined considering experimental design techniques. In order to study the relative impacts of the physical factors on the fuel cell voltage, some polarization curve results are selected from the static tests available applying experimental design methodology. First, several analyses are used to estimate the impact of the stack temperature, gas pressure, and stoichiometry rate on the fuel cell ...
A helium-3 proportional detector was equipped with the experiment of Liaw-type electrolytic cell contained eutectic LiCl-KCl molten salt saturated by LiD electrolytic to collect the informations of the rate and the energy distribution of possible neutron produced during the electrolysis processes. For long time monitoring, the significant reproducible neutron bursts appeared at several runs of cells during electrolytic processing. The neutron counting rate increased about a factor of two above the level of the background measurement. The pulse height signals were verified of neutron energy ranging from thermal up to 350 keV. (author).
A new band gap profile (exponential profile) for the active layer of the a-SiGe:H single junction cell has been designed and experimentally demonstrated. By computer simulations we show how bending the grading of the band gap in the i-layer contributes to the enhancement of the carrier collection, improving the fill factor and efficiency. The differences observed between experiments and simulations are studied using Rutherford Backscattering Spectrometry (RBS). The results highlight weak points during the deposition process, whose control enables us to bring together experimental and computational results.
A new simple multi-well plate-based assay to determine monocyte differentiation-inducing activity was developed. It is based on the increase of macrophage adherence after the induction of monocyte differentiation. The assay was conducted using a human monocytic leukemia cell line, THP-1, treated with either 12-O-tetradecanoylphorbol 13-acetate or cytokines, such as tumor necrosis factor-alpha and interferon-gamma. This method is sensitive and easy to perform, especially in case of analyzing a large number of samples. PMID:17920620
A new simple multi-well plate-based assay to determine monocyte differentiation-inducing activity was developed. It is based on the increase of macrophage adherence after the induction of monocyte differentiation. The assay was conducted using a human monocytic leukemia cell line, THP-1, treated with either 12-O-tetradecanoylphorbol 13-acetate or cytokines, such as tumor necrosis factor-? and interferon-?. This method is sensitive and easy to perform, especially in case of analyzing a large number of samples.
HEMATOLOGICAL MALIGNANCIES IN HUMANS TYPICALLY INVOLVE TWO TYPES OF GENETIC CHANGES: those that promote hematopoietic cell proliferation and survival (often the result of activation of tyrosine kinases) and those that impair hematopoietic cell differentiation (often the result of changes in transcription factors). The multi-stage erythroleukemia induced in mice by Friend spleen focus-forming virus (SFFV) is an excellent animal model for studying the molecular basis for both of these changes. Significant progress has been made in understanding the molecular basis for the multi-stage erythroleukemia induced by Friend SFFV. In the first stage of leukemia, the envelope protein encoded by SFFV interacts with and activates the erythropoietin (Epo) receptor and the receptor tyrosine kinase sf-Stk in erythroid cells, causing their Epo-independent proliferation, differentiation and survival. In the second stage, ...
To investigate the growth inhibitory effects, and the underlying mechanism of human colon cancer cell (HT-29) death, induced by a new synthetic bile derivative (HS-1200). Human colon cancer cells (HT-29), in exponential growth phase, were treated with various concentrations of a new synthetic bile acid derivative (HS-1200). The growth inhibitory effects on HT-19 cells were examined using a trypan blue exclusion assay. The extent of apoptosis was determined using agarose gel electrophoresis, TUNEL assays and Hoechst staining. The apoptotic cell death was also confirmed by Western blotting of PARP, caspase-3 and DNA fragmentation factor (DFF) analysis. To investigate the involvement of mitochondria, we employed immunofluorescent staining of cytochrome c and mitochondrial membrane potential analyses. The dose required for the half maximal inhibition (IC_5_0) of the HT-29 ...
Increased levels of epidermal growth factor receptor have been reported in a variety of tumors, including pulmonary squamous cell carcinomas in man. The purpose of this study was to determine if increased levels of epidermal growth factor (EGFR) were present in lung tumors from Beagle dogs that had been exposed to "2"3"9PuO_2- Using immunohistochemical techniques, sections from 17 lung tumors were examined for the presence of EGFR. Seven of the tumors were strongly positive for EGFR; the remainder of the tumors and the normal lung sections were negative. The positive immunostaining could not be correlated with the histologic phenotype of the tumors. Work is in progress to determine the level of EGFR in preneoplastic, proliferative epithelial foci in the Iung. (author)
Acute kidney injury (AKI) is a common complication after allogeneic stem cell transplantation (SCT). Although various risk factors for AKI have been reported, the influence of pretransplant comorbidity on the incidence of AKI has not been well investigated. We performed a retrospective analysis of 207 consecutive patients undergoing myeloablative or nonmyeloablative SCT between 2001 and 2009, using the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) as a representative of pretransplant comorbidities. According to Risk, Injury, Failure, Loss, and End-stage kidney disease (RIFLE) criteria, 158 patients (76.3%) developed AKI, and 92 patients (44.4%) developed severe AKI (RIFLE class I or class F) within 100 days after SCT. The cumulative incidence of severe AKI within 1...
A three-dimensional mathematical thermo-fluid model coupling the electrochemical kinetics with fluid dynamics was developed to simulate the heat and mass transfer in planar anode-supported solid oxide fuel cell (SOFC). The internal reforming reactions and electrochemical reactions of carbon monoxide and hydrogen in the porous anode layer were analyzed. The temperature, species mole fraction, current density, overpotential loss and other performance parameters of the single cell unit were obtained by a commercial CFD code (Fluent) and external sub-routine. Results show that the current density produced by electrochemical reactions of carbon monoxide cannot be ignored, the cathode overpotential loss is the biggest one among the three overpotential losses, and that the proper decrease of the operating voltage leads to the increase of the current density, PEN structure temperature, fuel utilization factor, fuel efficiency and ...
Spindle cell sarcomas consist of tumors with different biological features, of which distant metastasis is the most ominous sign for a poor prognosis. However, metastasis is difficult to predict on the basis of current histopathological analyses. We have identified actin filament-associated protein 1-like 1 (AFAP1L1) as a candidate for a metastasis-predicting marker from the gene expression profiles of 65 spindle cell sarcomas. A multivariate analysis determined that AFAP1L1 was an independent factor for predicting the occurrence of distant metastasis (P=0.0001), which was further confirmed in another set of 41 tumors by a quantitative mRNA expression analysis. Immunohistochemical staining using paraffin-embedded tumor tissues revealed that the metastasis-free rate was significantly better...
Histone deacetylase (HDAC) inhibitors have been actively exploited as potential anticancer agents. To identify gene targets of HDAC inhibitors, we found that HDAC inhibitors such as sodium butyrate, scriptaid, apicidin and oxamflatin induced the expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a potential cyclooxygenase-2 (COX-2) antagonist and tumor suppressor, in a time and concentration dependent manner in A549 and H1435 lung adenocarcinoma cells. Detailed analyses indicated that HDAC inhibitors activated the 15-PGDH promoter-luciferase reporter construct in transfected A549 cells. A representative HDAC inhibitor, scriptaid, and its negative structural analog control, nullscript, were further evaluated at the chromatin level. Scriptaid but not nullscript induced a signific...
Attacks by herbivorous insects reduce biomass production in willow plantations. The long-term goal of our research is to develop sustainable plant protection against these insect pests. Two lines of research are pursued. The first concentrates on identifying factors involved in the regulation of leaf-eating beetles. These insects vary in density among plantations, sometimes reaching outbreak levels resulting in complete defoliation. Mortality factors of eggs and larvae in plantations with low and high beetle densities have been investigated. The importance of plant resistance has also been investigated. The second line of research considers the mechanisms behind an earlier demonstrated resistance in certain willow clones against a gall midge. By using molecular techniques we have searched for markers of resistance. Promising results have been found concerning so called PR proteins; in particular chitinase seems to be ...
Before large-scale anthropogenetic emissions the environmental factors have been rather stable for thousands of years, varying yearly, seasonally and daily in rather regular manners around some mean values. In this century the emissions of CO{sub 2}, sulphur and nitrogen from society to atmosphere are changing both atmospheric and soil environment at rates not experienced before. The fluxes to soil affect the contents of plant available nutrients and solubility of toxic compounds in the forest soil. Additionally, the chemical state of soil environment is coupled to tree growth, litter production and nutrient uptake as well as to the activity of biological organisms in soil, which decompose litter and release nutrients from it. Trees have developed effective regulation systems to cope with the environment during the evolution. The resulting acclimations improve the functioning of the trees if the environmental factors remain ...
Functional activation of {beta}-catenin/Tcf signaling plays an important role in early events in carcinogenesis. We examined the effect of naringenin against {beta}-catenin/Tcf signaling in gastric cancer cells. Reporter gene assay showed that naringenin inhibited {beta}-catenin/Tcf signaling efficiently. In addition, the inhibition of {beta}-catenin/Tcf signaling by naringenin in HEK293 cells transiently transfected with constitutively mutant {beta}-catenin gene, whose product is not phosphorylated by GSK3{beta}, indicates that its inhibitory mechanism was related to {beta}-catenin itself or downstream components. To investigate the precise inhibitory mechanism, we performed immunofluorescence, Western blot, and EMSA. As a result, our data revealed that the {beta}-catenin distribution and the levels of nuclear {beta}-catenin and Tcf-4 proteins were unchanged after naringenin treatment. Moreover, the binding activities of Tcf complexes to ...
Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Mutations in PTEN-induced kinase 1 (PINK1) are a frequent cause of recessive PD. Autophagy, a pathway for clearance of protein aggregates or impaired organelles, is a newly identified mechanism for PD development. However, it is still unclear what molecules regulate autophagy in PINK1-silenced cells. Here we report that autophagosome formation is promoted in the early phase in response to PINK1 gene silencing by lentivirus transfer vectors expressed in mouse striatum. Reduced PP2A activity and increased phosphorylation of PP2A at Y307 (inactive form of PP2A) were observed in PINK1-knockdown dopaminergic cells and striatum tissues. Treatment with C2-ceramide (an agonist of PP2A) reduced autophagy levels in PINK...
The human CDC25 tyrosine phosphatases trigger activation of CDC2 by removing inhibitory phosphates; thus the genes encoding these phosphatases may be suspected as potential oncogenes due to their role in promoting cell division. To date, three human CDC25 genes have been identified: CDC25A, B, and C. This communication describes the mapping of CDC25A to chromosome 3p21 and CDC25B to chromosome 20p13 by fluorescence in situ hybridization with confirmation by the polymerase chain reaction of hamster-human somatic cell hybrid DNA. 3p21 is near an area frequently involved in karyotypic abnormalities in renal carcinomas, small cell carcinomas of the lung, and benign tumors of the salivary gland. 20p13 does not seem to be a common area for karyotypic alteration in tumors. Mapping of these genes to their chromosomal loci may help identify tumors with abnormal regulation of CDC25 genes due to genomic ...
We have constructed a 27-kDa hTERT C-terminal polypeptide (hTERTC27) devoid of domains required for telomerase activity and demonstrated that it is capable of nuclear translocation/telomere-end targeting. Here we showed that expression of a low level of hTERTC27 renders hTERT positive HeLa cells sensitive to H(2)O(2)-induced oxidative stress and subsequent cell senescence. The senescence-associated gene, the cyclin/cdk inhibitor p21(Waf1), was up-regulated. This occurs without changing the expression of endogenous hTERT, causing significant telomere shortening or inhibiting telomerase activity. Results from this study suggest for the first time that in addition to telomerase activity, the C-terminus of hTERT also plays a role in hTERT-mediated cellular resistance to oxidative stress. PMID:12565825
The goal of this paper is to explore how compliance with the Clean Air Act Amendments of 1990 (CAAA), especially Title IV and emission trading under it, will affect the current relationship between state and federal regulation. It is difficult, with the limited experience we have had under Title IV, to be definitive about or to be a very strong advocate of too many policy positions. What may be most helpful at this point is to identify where the difficult issues in state/federal relations might arise; and then to explore ways in which tensions might be either avoided or resolved. One anticipated conclusion is that a traditional regulatory mindset could be very destructive if applied to this new area of oversight without due sensitivity to what Congress is trying to achieve in Title IV. That concern pervaded the early legislative debates; and it persists today. Title IV presents some unique challenges to state regulators and will require some ...
The hypothesis of genetic defects in glycosaminoglycan (GAG) regulation among patients with insulin-dependent diabetes mellitus (IDDM) and nephropathy was assessed by studies in tissue cultures of fibroblasts obtained from 7 patients with normal urinary albumin excretion, 11 patients with diabetic nephropathy, and 6 nondiabetic control subjects. The incorporation of (2H) glucosamine and (35S) sulfate into hyaluronic acid (HA), chondroitin sulfate and dermatan sulfate (CS + DS), and heparan sulfate (HS) was measured in cells, matrix, and medium and related to micrograms of tissue protein. Large interindividual variations were seen in all three groups, and the incorporation of (3H) glucosamine into HA, CS + DS, and HS and (35S) sulfate into CS + DS and HS were not significantly different between the three groups. However, the fractional incorporation of (3H)glucosamine into HS was significantly reduced in diabetic patients with nephropathy ...
Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) chemicals are antitumor antibiotics inhibiting nucleic acid synthesis. An indole carboxylate-PBD hybrid with six-carbon spacer structure (IN6CPBD) has been previously demonstrated to induce melanoma cell apoptosis and reduce metastasis in mouse lungs. This study aimed at investigating the efficacy of the other hybrid compound with four-carbon spacer (IN4CPBD) and elucidating its anti-metastatic mechanism. Human melanoma A375 cells with IN4CPBD treatment underwent cytotoxicity and apoptosis-associated assays. Transwell migration assay, Western blotting, and ELISA were used for mechanistic study. IN4CPBD exhibited potent melanoma cytotoxicity through interrupting G1/S cell cycle progression, increasing DNA fragmentation and hypodipoidic DNA contents, a...
The activation of nuclear factor-kappa B1 (NFκB1) in cancer cells may confer resistance to ionizing radiation (IR). To enhance the therapeutic efficiency of IR in lung cancer, we screened for...Full Text Available
In both type 1 and type 2 diabetes, pancreatic islet dysfunction results in part from cytokine-mediated inflammation. The ubiquitous eukaryotic translation initiation factor 5A (eIF5A), which is the...Full Text Available
Werner syndrome (WS) is a rare disorder characterized by the premature onset of several pathologies associated with aging. The gene responsible for WS codes for a RecQ-type DNA helicase and is believed...Full Text Available
The aim of this study is to determine the effects of silver nanoparticles (Ag-NP) on vascular endothelial growth factor (VEGF)-and interleukin-1 beta (IL-1β)-induced vascular permeability, and...Full Text Available
The Epstein-Barr virus protein, LMP1, is a functional mimic of the cellular receptor CD40, but signals to B lymphocytes in an amplified and sustained manner compared to CD40. LMP1 contributes...Full Text Available
DescriptionIron deficiency anaemia is a common problem and may be particularly important to certain groups of vegetarians. This project investigates isolating and identifying iron-binding constituents of meat digests using human Caco-2 cell lines. Stable isotope techniques used to test whether one or more of these compounds enhance iron absorpion in vivo and could therefore be added to vegetarian products to imporve iron nutrition.
BackgroundHerpes simplex virus type-1 (HSV-1) infections can cause a number of diseases ranging from simple cold sores to dangerous keratitis and lethal encephalitis. The interaction...Full Text Available
Amplification of oncogenes has been found to be an important prognostic factor in behavior of patients' malignancies. In this study we have used new gel electrophoresis techniques to follow the location...Full Text Available
This report for the Swiss Federal Office of Energy (SFOE) presents the overview reports made by SFOE Heads of Program on work done in 2007. Projects reported on in the natural gas-fired fuel cell area include the EU-project REAL-SFOC, the long-term testing of anode-supported SOFC stacks, intermediate-temperature fuel cells based on proton conducting electrolytes, the interdisciplinary ONEBAT project and lifetime-enhancement of SOFC stacks for CHP applications. In the polymer-electrolyte fuel cell (PEFC) area, projects concerning proton-conducting polymer membranes, factors limiting the lifetime of fuel cell membranes, a new highly active oxygen reduction electrode for PEM fuel cell and zinc/air battery applications, the enhancement of PEFC durability and reliability, model-based investigation of PEFC performance, and local gas analysis of PE fuel ...
Transcriptional regulation of the galactose-metabolizing genes in Saccharomyces cerevisiae depends on three core proteins: Gal4p, the transcriptional activator that binds to upstream activating DNA sequences (UASGAL); Gal80p, a repressor that binds to the carboxyl terminus of Gal4p and inhibits transcription; and Gal3p, a cytoplasmic transducer that, upon binding galactose and adenosine 5'-triphosphate, relieves Gal80p repression. The current model of induction relies on Gal3p sequestering Gal80p in the cytoplasm. However, the rapid induction of this system implies that there is a missing factor. Our structure of Gal80p in complex with a peptide from the carboxyl-terminal activation domain of Gal4p reveals the existence of a dinucleotide that mediates the interaction between the two. Biochemical and in vivo experiments suggests that nicotinamide adenine dinucleotide phosphate (NADP) plays a key role in the initial induction event.
This report surveys the possibilities and restrictions of different construction materials for the purpose of the blades of a small stall regulated turbine. For example scaling up, material saving at decreasing of static or dynamic loads, comparisons of global costs based on prices per unit of weight, etc. For the mutual comparison of construction materials for turbine blades the starting point is a stall regulated horizontal axis turbine with a rotor diameter of 16 m and a tipvane speed of about 64 m/s. Short descriptions are given of the materials and of the applied production methods with the resulting blade geometry. The blade skins are dimensionized for storm loads after the optimalization of the blade geometry, needed for the design wind speed, is recorded. The resulting blade skins are mutually compared as for weight, mass inertia and bending stiffness. Also a comparison took place of the resulting reserve factors ...
The predicted results of INDAC code were compared with measured {sup 3}H concentrations in air and pine-needle around the Wolsung site. The optimal sets of input data to INDAC were in addition selected by comparing the measured values with the predicted values of INDAC based on various conditions such as the release modes of effluents into the environment, the classification of wind classes, and the consideration of terrain. The predicted {sup 3}H concentrations in air and pine-needle were shown to have good agreement with measured values, although there are some limitations such as uncertainties in measured values, complex topology around the site, and the land-sea breeze effects. The assumption on the {sup 3}H behavior in vegetables or plants that the ratio of {sup 3}H concentration in plant water to {sup 3}H concentration in atmospheric water is 1/2 was shown to be conservative in terms of the audit calculation performed by the regulator. It was also found that ...
The predicted results of INDAC code were compared with measured "3H concentrations in air and pine-needle around the Wolsung site. The optimal sets of input data to INDAC were in addition selected by comparing the measured values with the predicted values of INDAC based on various conditions such as the release modes of effluents into the environment, the classification of wind classes, and the consideration of terrain. The predicted "3H concentrations in air and pine-needle were shown to have good agreement with measured values, although there are some limitations such as uncertainties in measured values, complex topology around the site, and the land-sea breeze effects. The assumption on the "3H behavior in vegetables or plants that the ratio of "3H concentration in plant water to "3H concentration in atmospheric water is 1/2 was shown to be conservative in terms of the audit calculation performed by the regulator. It was also found that data sets based on mixed ...
Salamanders regenerate their appendages after amputation and nerves are required for this process. Experiments were designed to test the idea that one way nerves could affect blastema cell proliferation is by influencing the metabolism of extracellular matrix (ECM) components and to identify neurotrophic factors which promote blastema cell mitosis. Temporal and spatial differences of glycosaminoglycans (GAGs) synthesis is innervated and denervated limbs were examined. Hyaluronic acid (HA) was found to be the major GAG produced during the proliferative period and chondroitin sulfate during differentiation. Denervation reduced synthesis of both these components by half. Dorsal root ganglia and fibroblast growth factor (FGF), a brain-derived mitogen, similarly doubled GAG synthesis in cultured blastemas, the FGF-effect being primarily on HA production. Histochemical and autoradiographical results confirmed ...
Shewanella oneidensis MR-1 is a model environmental organism that possesses diverse respiratory capacities, including the ability to reduce soluble Cr(VI) to sparingly soluble, less toxic Cr(III). Effective bioremediation of Cr-contaminated sites requires knowledge of the molecular mechanisms and regulation of heavy metal resistance and biotransformation by dissimilatory metal-reducing bacteria. Towards this goal, our ERSP-funded work is focused on the identification and functional analysis of genes/proteins comprising the response pathways for chromate detoxification and/or reduction. Previous transcriptomic profiling and whole-cell proteomic analyses implicated the involvement of a functionally undefined DNA-binding response regulator (SO2426) and a putative azoreductase (SO3585) in the chromate stress response of MR-1. Here we describe a detailed functional analysis of SO2426 and SO3585 in order to begin to understand ...
This report covers the first year of operation of a fuel cell power plant, installed by PPL Spectrum, Inc. (PPL) under contract with the United States Coast Guard (USCG), Research and Development Center (RDC). The fuel cell was installed at Air Station Cape Cod in Bourne, MA. The project had the support of the Massachusetts Technology Collaborative (MTC), the Department of Energy (DOE), and Keyspan Energy. PPL selected FuelCell Energy, Inc. (FCE) and its fuel cell model DFC{reg_sign}300 for the contract. Grant contributions were finalized and a contract between PPL and the USCG for the manufacture, installation, and first year's maintenance of the fuel cell was executed on September 24, 2001. As the prime contractor, PPL was responsible for all facets of the project. All the work was completed by PPL through various subcontracts, including the primary subcontract with FCE ...
The present study was undertaken to determine the involvement of calcium-protein kinase C pathway in the mechanism of action of Escherichia coli heat stable enterotoxin (STa) apart from STa-induced activation of guanylate cyclase in human colonic carcinoma cell line COLO-205, which was used as a model cultured cell line to study the mechanism of action of E. coli STa. In response to E. coli STa, protein kinase C (PKC) activity was increased in a time-dependent manner with its physical translocation from cytosol to membrane. Inhibition of the PKC activity in membrane fraction and inhibition of its physical translocation in response to IP_3-mediated calcium release inhibitor dantrolene suggested the involvement of intracellular store depletion in the regulation of PKC activity. Among different PKC isoforms, predominant involvement of calcium-dependent protein kinase C (PKC#alpha#) was specified using isotype-specific ...
To evaluate the predictive factors for treatment response and prognostic factors affecting survival outcomes after concurrent chemoradiotherapy (CCRT) for patients with anal squamous cell carcinoma. Medical records of forty two patients with histologically confirmed analsquamous cell carcinoma, who had complete CCRT between 1993 and 2008, were reviewed retrospectively. Median age was 61.5 years (39-89 years), and median radiotherapy (RT) dose was 50.4 Gy (30.0-64.0 Gy). A total of 36 patients had equal to or less than T2 stage (85.7%). Fourteen patients (33.3%) showed regional nodal metastasis, 36 patients (85.7%) were treated with 5-fluorouracil (5-FU) plus mitomycin, and the remaining patients were treated by 5-FU plus cisplatinum. The median follow--up time was 62 months (2-202 months).The 5-year overall survival, locoregional relapse-free survival, disease-free survival, and colostomy-free survival ...
A preliminary investigation was conducted on ion specific membranes. This investigation concentrated on testing candidate organic compounds for transporting cesium ions through a membrane composed of the organic compound supported on a substrate. Solid PVC membranes were initially tried, but were found to be too slow. Thereafter, only liquid membranes were tested. These were faster and cesium concentration factors up to 2.96 were achieved in a single membrane cell. A cell with two membranes achieved a cesium concentration factor of 4.19. Cesium precipitation with sodium tetraphenyl borate in high sodium concentrations was explored. No interference from sodium was found until the sodium nitrite concentration reached 4.5 moles. Concurrently, cesium concentrations as high as 5.4 g/L were precipitated. Potassium tetraphenyl borate is being investigated for use in exchange columns for the removal of cesium ...
A preliminary investigation was conducted on ion specific membranes. This investigation concentrated on testing candidate organic compounds for transporting cesium ions through a membrane composed of the organic compound supported on a substrate. Solid PVC membranes were initially tried, but were found to be too slow. Thereafter, only liquid membranes were tested. These were faster and cesium concentration factors up to 2.96 were achieved in a single membrane cell. A cell with two membranes achieved a cesium concentration factor of 4.19. Cesium precipitation with sodium tetraphenyl borate in high sodium concentrations was explored. No interference from sodium was found until the sodium nitrite concentration reached 4.5 moles. Concurrently, cesium concentrations as high as 5.4 g/L were precipitated. Potassium tetraphenyl borate is being investigated for use in exchange columns for the removal of cesium ...
Purpose/Objective: The role of programmed cell death (apoptosis) as a cellular response to cancer therapy such as radiation or chemotherapy is the subject of much study, and manipulation of the apoptotic response in tumor cells may be valuable in the treatment of a variety of cancers. Both p53 dependent and independent apoptotic pathways have been identified; p53 is mutated in at least 50 % of human cancers and a majority of radiation resistant tumors contain p53 mutations. This study is designed to examine the induction of programmed cell death in a human colon carcinoma cell line that possesses two mutated p53 alleles. Ionizing radiation alone, or in combination with the chemotherapeutic drug 5-fluorouracil (5-FU), were used to elicit the apoptotic response. This study will focus on whether these treatments can induce a significant apoptotic response in cells that have mutated p53 ...
Full text: The general population is daily exposed to chronic, low doses of ionizing radiation (IR) from both natural and artificial sources. The biological consequences of acute, high dose IR exposure can be readily determined; however, the nature and significance of low dose, low dose-rate IR effects are still the subject of debate. Confounding the issue, are the phenomena collectively referred to as the Radiation-induced Bystander Effect (RIBE). The RIBE describes a collection of in vitro observations that suggest the presence of a soluble, transmissible factor(s) released from irradiated cells that can induce a biological response in un-irradiated cells. The induction, nature and magnitude of the RIBE varies between cell culture systems, radiation sources and end-points measured. Efforts to confirm the presence of the RIBE in vivo have been confined to in vivo-like culture systems and limited work ...
An analogue of hGH isolated from plerocercoids of the tapeworm Spirometra mansonoides displaces ["1"2"5I]hGH from its receptors in rabbit, rat, and hamster liver membranes. Biologically, plerocercoid growth factor (PGF) is more similar to hGH than to other mammalian GH's but has not been shown to bond human cells. Receptors specific for hGH have been described on cultured human lymphocytes (IM-9). In this study, the authors compared the binding of PGF and hGH in IM-9 cells and in rabbit hepatic membranes. IM-9 lymphocytes (12 x 10"6 cells/tube) were incubated with ["1"2"5I]hGH and increasing concentrations of hGH (ng/ml) or PGF (serial dilutions) for 90 min at 30"0 C. Specific binding (B_0 - NSB) was determined for each dose of hGH or PGF and the binding curves were analyzed by logit-log regression. The results show that PGF displaced ["1"2"5I]hGH from human cells in a dose ...
Radio-biologists have pointed out a novel radiobiological phenomenon observed in many tumor and normal cell lines: hyper-radiosensitivity to very low-dose (H.R.S.) followed by induced radioresistance (I.R.R.) after a threshold dose of 0.1-0.3 Gy that depends on the cell line. Radioresistance at high dose (i.e. higher than 0.5 Gy) and metastatic potential of tumor cells are likely major factors of failure in radiotherapy. A careful review of literature suggests that: 1) radiotherapy does not increase the metastatic potential of tumor cells; 2) radioresistance at high dose and metastatic potential are not related. However, inside a given tumor cell line, highly metastatic clones may elicit more cells showing H.R.S; or are more radiosensitive at high dose than poorly metastatic ones. Recent data obtained from molecular techniques (comet and ...
The importance of cellular dosimetry in both diagnostic and therapeutic nuclear medicine is becoming increasingly recognized. Experimental range-energy relations for electrons and alpha particles, along with derived geometric reduction factors, are used to calculate cellular absorbed fractions for these radiations. The resulting absorbed fractions are employed to calculate cellular S-values for several radionuclides. Cellular absorbed fractions for monoenergetic electron sources with energies ranging from 0.1 keV to 1 MeV, distributed uniformly in the source region, are calculated for several target {l_arrow} source combinations including cell{l_arrow}cell, cell{l_arrow}cell surface, nucleus{l_arrow}nucleus, nucleus {l_arrow}cytoplasm and nucleus {l_arrow}cell surface. Similar data are also provided for monoenergetic alpha particle sources with energies ranging from 3 to 10 MeV. S-values are also ...
The University of Maryland at Baltimore was awarded a grant from the Department of Energy to test a specially modified incinerator to burn biomedical radioactive waste. In preparation for the incinerator, the Radiation Safety Office devised a comprehensive plan for its safe and effective use. The incinerator plan includes a discussion of regulations regarding on-site incineration of radioactive waste, plans for optimum use in burning four principal waste forms, controlled air incineration technology, and standard health physics safety practices; a use plan, including waste categorization and segregation, processing, and ash disposition; safety procedures, including personnel and area monitoring; and methods to evaluate the incinerator's effectiveness by estimating its volume reduction factors, mass and activity balances, and by determining the cost effectiveness of incineration versus commercial shallow land burial.
Abstract Capillary permeability is a tightly regulated feature of microcirculation in all organ beds. In sepsis, this feature is fundamentally altered. We have previously reported elevated levels of angiopoietin-2 in patients with septic shock, and have investigated tumor necrosis factor (TNF)-related and weak inducer of apoptosis (TWEAK), which mediates both angiogenesis and inflammation, in those patients. Enzyme-linked immunoassay was used to measure serum TWEAK levels in 20 patients with septic shock, all of whom were treated by direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX), and in 20 non-septic controls. The TWEAK levels were higher in patients with septic shock (192.8--230.5-pg/mL) than in controls (84.1--28.7-pg/mL, P-=-0.043). Between 11 survivors and 1...
In quantifying health risks arising from radiation exposure and synergistic effects promoted by radiation the dose-effect relationship must be used as a basis. Special problems arise in the extrapolation of experimental results or in the treatment of data in the region of low doses administered over long periods of time. For radiation protection purposes, especially manifestations of cancer and genetic effects are significant. The International Commission on Radiation Protection has published binding guiding values on the basis of which to assess the risk of cancer. The cancer risk and genetic risks are estimated for relevant dose ranges and compared with other factors of civilization. For the most important chemical pollutants emitted into the environment the possibilities of impacts arising from synergistic effects are discussed on the basis of the rules and regulations specified in German antipollution legislation. (orig.) 891 HP/orig. 892 ...
To sophisticate the nuclear fuel recycling processes, the transfer percentages for Pd, Mo, Te, and Sb should be determined. Each element solution containing NaNO_3 or HNO_3 was fed consistently into the thin film evaporator regulated in vac and at 50 deg C. The analyte percentages in the inside of the lid, in the condenser, and in the distillate were 10"-"1%/m"2, 10"-"3%/m"2, and 10"-"3% (DF = 10"5), respectively. The Mo percentage in the condenser was lower by a factor of 10 than those of other elements investigated. The NO_3"- percentages were nearly constant despite increasing HNO_3 concentrations, however, the ratios decreased with increasing NaNO_3 concentrations. (author)
Purpose: To provide a feedwater control device capable of minimizing the adverse response of steam drum level at low power. Consitution: In order to perform feedwater control at low power by the substantial control of three factors, that is, main steam flow rate, feedwater flow rate and steam drum level, the main steam flow rate is determined from the reactor output and feedwater rate is determined from the changes in the feedwater temperature due to the mixing of waters in the reactor clean up system and feedwater. If a difference is resulted between these flow rates, a starting feedwater regulator is controlled instantly to eliminate the difference. The water level in the steam drum is used for amending the difference from the final set value of the drum water level, by which the adverse response of the steam drum level can be minimized. (Seki, T.).
Material degradation of pressure tubes, which are the most important components in CANDU fuel channel, can only be evaluated by removing and examining them(material surveillance). This study aimed at establishment of overall evaluation technology including the evaluation of the material degradation for the integrity of pressure tubes of Wolsung units. Material tests for pressure tubes were performed as follows; (1) Evaluation on life limiting factors of pressure tubes (2) Review on leak-before-break and integrity maintenance technology of pressure tubes (3) Survey on selection criteria for tubes to be inspected and on related regulations for material surveillance (4) Analysis of material surveillance test procedure (5) Basic examinations of Wolsung unit 1 pressure tube material(TEM, texture, chemical component etc) (6) Manufacture of test equipments and test (DHCV, hydriding, grip and tensile specimen etc). 23 figs, 6 tabs, 59 refs. (Author).
;Table of Contents: Legal authority; Summary of proposed regulations; Industry definition and waste streams; Industry description; Data and information gathering; Selection of pollutant parameters; Drilling wastes-characterization, control, and treatment technologies; Produced water-characterization, control, and treatment technologies; Miscellaneous waste-characterization, control, and treatment technologies; Cost and pollutant loading determination of drilling fluids and drill cuttings; Compliance cost and pollutant load determination of produced water; Compliance cost and pollutant load determination of well treatment, workover, and completion fluids; Cost and pollutant loading determination of deck drainage; Options selection-rationale and total costs; Pretreatment standards; Non-water quality environmental impacts and other factors; Best Management Practices; and Appendices.
After having discussed the peculiarities of children in X-ray diagnosis the application of the effective as well as the mean equivalent doses as to the determination of the radiation exposure in children is represented. In using computerized tomograms to determine position and extent of an organ the exposure by repeated X-raying was calculated referring to the entrance dose. Entrance dose measurements for all types of X-ray examination in hospitals and ascertainments of the frequency of radiograms in 20 X-ray departments were used to determine per capita and collective doses, resp., in several age groups. Alltogether, the per capita dose of children in the GDR amounts to 30% of that of adults. Conclusions were drawn as to taking measures to further reduction of radiation exposure: (1) Technical measures, such as positioning of patients, shielding of organs, quality assurance; (2) elaboration of regulations concerning the execution of X-raying in children and ...
Linear and nonlinear state feedback controllers are proposed to control the bifurcation of a phenomenon in power system, this phenomenon of electro-mechanical interaction between the series resonant circuits and torsional mechanical frequencies of the turbine-generator sections, which known as subsynchronous resonance (SSR). The first system of the IEEE second benchmark model is considered. The dynamics of the two axes damper windings, automatic voltage regulator and power system stabilizer are included. The linear controller gives better initial disturbance response than that of the nonlinear, but in a small narrow region of compensation factors. The nonlinear controller not only can be easily implemented, but also it stabilizes the operating point for all values of the bifurcation parameter.
First generation biofuels provide a number of ecosystem services (e.g., fuel, climate regulation) but they also compromise other ecosystem services (e.g., food, freshwater services) which are of paramount value to human wellbeing. However, this knowledge is fragmented and little is known about how the ecosystem services provided and/or compromised by biofuels link to human wellbeing. In fact, whether biofuels production and use can have a negative or positive impact on the environment and society depends on several interconnected factors. This paper provides a critical review of the drivers, impacts and tradeoffs of biofuel production and use. In particular, it rationalizes the evidence coming from diverse academic disciplines and puts it into perspective by employing the ecosystem service...
The book presents a very good account of all aspects of protection from ionizing radiation. The quantities and units are given and defined used in nuclear physics and dosimetry. The effects of ionizing radiation on cells and on man are described. The principles are presented of radiation protection including limits and valid regulations and decrees. Also discussed is internal irradiation and its modelling. A great part of the book is devoted to aspects of monitoring persons, the living and working environment and to the determination of internal contamination. The system of radiation protection in Czechoslovakia is described and some practical questions are discussed of protection during radiodiagnosis and radiotherapy, in the nuclear fuel cycle, in the operation of nuclear power installations and in crack detection. In conclusion a survey is given of the population exposure from various natural and artificial sources. (M.D.). 57 figs., 34 ...
Many higher plants produce economically important organic compounds such as oils, resins, tannins, natural rubber, gums, waxes, dyes, flavors and fragrances, pharmaceuticals, and pesticides. However, most species of higher plants have never been described, much less surveyed for chemical or biologically active constituents, and new sources of commercially valuable materials remain to be discovered. Advances in biotechnology, particularly methods for culturing plants cells and tissues, should provide new means for the commercial processing of even rare plants and the chemicals they produce. These new technologies will extend and enhance the usefulness of plants as renewable resources of valuable chemicals. In the future, biologically active plant-derived chemicals can be expected to play an increasingly significant role in the commercial development of new products for regulating plant growth and for insect and weed control. 65 references.
Abstract In the 1990s, significant efforts were invested in the research and development of food-grade expression systems in lactic acid bacteria (LAB). At this time, Lactococcus lactis in particular was demonstrated to be an ideal cell factory for the food-grade production of recombinant proteins. Steady progress has since been made in research on LAB, including Lactococcus, Lactobacillus and Streptococcus, in the areas of recombinant enzyme production, industrial food fermentation, and gene and metabolic pathway regulation. Over the past decade, this work has also led to new approaches on chromosomal integration vectors and host/vector systems. These newly constructed food-grade gene expression systems were designed with specific attention to self-cloning strategies, food-grade selection...
Apelin is a peptide known as the ligand of the G-protein-coupled receptor APJ. Several active apelin forms exist such as apelin-36, apelin-17, apelin-13, and the pyroglutamated form of apelin-13. Apelin and APJ are expressed in the central nervous system, particularly in the hypothalamus and in many peripheral tissues. Apelin has been shown to be involved in the regulation of cardiovascular and fluid homeostasis, food intake, cell proliferation, and angiogenesis. In addition to be an ubiquitous peptide, apelin is also produced and secreted by adipocytes and thus considered as an adipokine. This has opened a new field of investigation establishing a link between apelin and metabolic disorders (obesity, type 2 diabetes, etc.) which is the focus of the present review. Several studies, but not...
Since Classical Antiquity numerous authors have linked the origin of some mental disorders to physical and functional changes in the pineal gland because of its attributed role in humans as the connection between the material and the spiritual world. The pineal organ was seen as a valve-like structure that regulated the flow of animal spirits through the ventricular system, a hypothesis that took on more vigour during the Middle Ages and the Renaissance. The framework for this theory was ''the three cells of the brain'', in which the pineal gland was even called the ''appendix of thought''. The pineal gland could also be associated with the boom, during this period, of certain legends about the ''stone of folly''. But the most relevant psychopathological role of this organ arrived with Des...
PACAP (pituitary adenylate cyclase activating polypeptide) is widely distributed neuropeptide acting via three subtypes of receptors, PAC(1), VPAC(1) and VPAC(2). Here we examined the localisation and nature of PACAP-immunoreactive nerves in the rat thyroid and parathyroid glands and defined the distribution of PAC(1), VPAC(1) and VPAC(2) receptor mRNA's. In the parathyroid gland a large number of nerve fibres displaying PACAP-immunoreactivity were distributed beneath the capsule, around blood vessels and close to glandular cells. Most of the PACAP-nerves were sensory, since they co-stored CGRP (calcitonin-gene-related peptide) and were sensitive to capsaicin-treatment. mRNA's for PAC(1) and VPAC(2) receptors occurred in the parathyroid gland, mainly located in the glandular cells. In the thyroid gland PACAP-immunoreactive nerve fibres were associated with blood vessels, thyroid follicles and parafollicular C-cells. A high ...
Apoptosis, or programmed cell death (PCD), is a fundamental process that protects organismal integrity. In earlier work, we demonstrated that over-expression of either of two anti-apoptotic members of the BCL-2 family (BCL-2 or BCL-X L could elevate the frequency of radiation-induced mutations at the autosomal TK1 locus in human TK6 lymphoblasts that express wild-type TP53. Ectopic expression of BCL-X L also elevated the frequencies of double-strand break-induced gene conversion. The purpose of this study is to determine if BCL-2 family proteins promote radiation mutagenesis indirectly through their suppression of PCD, or whether the 'pro-mutagenic' function of these proteins can be separated from their anti-apoptotic function. We developed stable transfectants of TK6 cells that express a mutated form of BCL-X L with a single amino acid substitution in the BH1 domain that is known to interfere with the ability to suppress PCD (BCL-X L ...
Objective: To study the effects of minocycline hydrochloride (MINO) on the formation of tartrate-resistant acid phosphatase (TRAP) staining-positive multinucleated osteoclast-like cells in mouse bone marrow cells (BMCs) treated with 1@a,25(OH)"2D"3 or soluble receptor activator of nuclear factor-@kB ligand (s-RANKL). Materials and methods: Mouse BMCs were cultured in alpha-modified minimum essential medium containing foetal calf serum (10%) and tetracyclines (2.5, 5 and 10@mM), such as MINO, tetracycline hydrochloride (TC), oxytetracycline hydrochloride (OXT) or doxycycline (DOXY) in the presence of 1@a,25(OH)"2D"3 (10nM) or s-RANKL (20ng/ml) for 7 days, and the number of TRAP staining-positive osteoclast-like cells was counted. In RNA isolated from BMCs treated with 1@a,25(OH)"2D"3 or s-R...
Somatogenic hormones play an important role in regulation of receptors for prolactin (PRL) and estrogen. Plerocercoids of the tapeworm, S. mansonoides produce a factor which mimics some, but not all of the actions reported for GH. Intact female rats were subjected to a constant infusion of plerocercoid growth factor (PGF) via a subcutaneous infection for two weeks to determine if PGF influences receptors for PRL, GH or estradiol. The rate of weight gain in the PGF-treated rats was accelerated in spite of a marked reduction in serum GH. Partially-purified PGF specifically displaced [125I]hGH from rat liver receptors but microsomes prepared from rats treated with PGF specifically bound significantly less [125I]hGH than microsomes from control rats. The reduction in [125I]hGH binding was not due to occupancy or to a change in affinity but to a suppression in receptor concentration. Scatchard analysis of [3H]estradiol binding ...
This paper examines the dynamic international political economic environment in which petroleum exploration and production companies must operate when considering investments in the economically transitional nations of the former Soviet Union or developing nations In this period of critical global changes low oil prices is only one factor with which petroleum companies Must be. concerned in their investment decisions Other factors include the transition from a bipolar world to a multipolar world of free trade zones. the general malaise of the international economy public and political recognition that nations and industries can no longer practice environmental {open_quotes}beggar-thy-neighbor{close_quotes} policies, and the rejection of aggregate national economic growth policies for sustainable economic development policies in both the Developed and developing world This paper focuses on actions which investing petroleum exploration and ...
Tissue factor pathway inhibitor (TFPI), a protease inhibitor that circulates in association with plasma lipoproteins (VLDL, LDL and HDL), helps to regulate the extrinsic blood coagulation cascade. The authors have cloned a 125-kb genomic region containing the entire human TFPI gene on six overlapping cosmids and prepared a restriction map of this contig to clarify gene structure. More than half (45 kb) of the 85-kb gene is occupied with 5[prime] noncoding elements: coding begins at exon 3. A HindIII RFLP identified with one cosmid was genotyped in the CEPH panel of 559 reference families. Linkage analysis using markers on human chromosome 2 located the TFPI gene on 2q, 36 cM proximal to D2S43(pYNZ15) and 13 cM distal to the crystalline [gamma]-polypeptide locus CRYGP1(p5G1). 31 refs., 3 figs., 3 tabs.
Cytosine methylation in DNA is a major epigenetic signal, and plays a central role in propagating chromatin status during cell division. However the mechanistic links between DNA methylation and histone methylation are poorly understood. A multi-domain protein UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) is required for DNA CpG maintenance methylation at replication forks, and mouse UHRF1-null cells show enhanced susceptibility to DNA replication arrest and DNA damaging agents. Recent data demonstrated that the SET and RING associated (SRA) domain of UHRF1 binds hemimethylated CpG and flips 5-methylcytosine out of the DNA helix, whereas its tandom tudor domain and PHD domain bind the tail of histone H3 in a highly methylation sensitive manner. We hypothesize that UHRF1 brings the two components (histones and DNA) carrying appropriate markers (on the tails of H3 and hemimethylated CpG sites) ready to be assembled into a ...
The effects of muscarinic agonists and diisopropylfluorophosphate (DFP) on muscarinic receptor density and muscarinic receptor-mediated responses was assessed in mouse brain and mouse neuroblastoma cells (clone N1E-115). Utilizing the antagonist ({sup 3}H)quinuclidinyl benzilate (({sup 3}H)QNB), there was no difference in the maximal binding capacity (B{sub max}) or equilibrium dissociation constant (K{sub d}) between untreated and 24 hour DFP-treated mice. However, one administration of DFP produced a 24% and 33% decrease in B{sub max} measured by ({sup 3}H)N-methylscopolamine (({sup 3}H)NMS) after 18 and 24 hours which was rapidly reversible within 36 hours after DFP treatment. The loss of ({sup 3}H)NMS binding sites following acute DFP treatment was not accompanied by a change in a particular muscarinic receptor binding conformation. Furthermore, the magnitude of muscarinic receptor-mediated phosphoinositide hydrolysis was unchanged following short-term DFP ...
To investigate mechanisms responsible for positive and negative transcriptional control, the authors have utilized two types of promoters that are diffferentially regulated by thyroid hormone (T{sub 3}) receptors. Promoters containing the palindromic T{sub 3} response element TCAGGTCA TGACCTGA are positively regulated by the T{sub 3} receptor after the administration of T{sub 3}, whereas otherwise identical promoters containing the estrogen response element TCAGGTCA CTG TGACCTGA can be regulated negatively; converse effects are observed with the estrogen receptor. They describe evidence that the transcriptional inhibitory effects of the T{sub 3} or estrogen receptors on the estrogen or T{sub 3} response elements, respectively, are imposed by amino acid sequences in the C'-terminal region that colocalize with dimerization and hormone-binding domains and that these sequences can transfer inhibitory functions to other ...
The insulin signaling pathway, involving protein kinase B (PKB) and mitogen-activated protein kinase (MAPK), mediates the biological response to insulin and several growth factors and cytokines. To investigate the correlation between glucose transporter (Glut) biosynthesis and the insulin signaling pathway activated by novel compounds of Liriope platyphylla (LP9M80-H), alterations in Glut and key protein expression in the insulin signaling pathway were analyzed in the liver and brain of ICR mice treated with LP9M80-H. An in vitro assay showed that the highest level of insulin concentration was observed in the LP9M80-H-treated group, followed by the LP-H, LP-M, LP-E, and LP9M80-C-treated groups. Therefore, LP9M80-H was selected for use in studying the detailed mechanism of the insulin signaling pathway in animal systems. In an in vivo experiment, LP9M80-H induced a significant increase in glucose levels and a decrease of insulin concentration in the blood of mice, ...
The patients studied were referred for routine abscess localization with indium-111 labelled autologous leukocytes. One series (n=15) was studied at 1 day after reinjection of labelled cells and a second series (n=9) was studied between 4 hours and 4 days after reinjection of labelled cells. The leukocytes were isolated by a gravity sedimentation method and labelled with In-111 oxinate according to Roevekamp and co-workers. The labelled cell suspension administered to the patient contained between 11 and 15 MegaBq (300-400 microCi). The indium-111 concentration in the liver and spleen was quantitated using a scintillation camera and an on-line computer system. Phantom studies were carried out to obtain conversion factors from geometric mean counts to MegaBq of activity for both liver and spleen. Once determined, the amount of activity in liver and spleen was corrected for physical decay of In-111 and ...
The authors have found that heat-inactivated serum (57/sup 0/C for 1 hour) from normal chickens reduces the proliferation of mitogen-stimulated chicken and murine splenocytes as well as some transformed mammalian lymphoblastoid cell lines. Greater than a 50% reduction in /sup 3/H-thymidine incorporation was observed when concanavalin A (Con A)-activated chicken splenocytes that were cultured in the presence of 10% autologous or heterologous serum were compared to mitogen-stimulated cells cultured in the absence of serum. Normal chicken serum (10%) also caused greater than 95% suppression of /sup 3/H-thymidine incorporation by bovine (EBL-1 and BL-3) and gibbon ape (MLA 144) transformed lymphoblastoid cell lines. The only cell line tested that was not inhibited by chicken serum was an IL-2-dependent, murine cell line. Chicken serum also inhibited both /sup 3/H-thymidine incorporation ...
The performance of two-cell planar solid oxide fuel cell stacks using coal syngas, with and without hydrogen sulfide (H{sub 2}S), was studied. All cells were tested at 850 C with a constant current load of 15.2 A (current density of 0.22 A cm{sup -2} per cell) and 30% fuel utilization. The H{sub 2}S injection immediately and significantly affected the power degradation of the stack system regardless of the carrier fuel. Results for the test with only H{sub 2} and N{sub 2} in the presence of H{sub 2}S (119-120 ppm) indicated that the power decay and area-specific resistance (ASR) degradation values were lower than those for the tests where simulated syngas containing CO and increased water content was used. The results indicate that contact points in the stack contributed to the power degradation of the system. Other factors, including contamination from the upstream fuel gas tubing, ...
Extracellular matrix (ECM) comprises a rich meshwork of proteins and proteoglycans, which not only contains biological cues for cell behavior, but is also a reservoir for binding growth factors and controlling their release. Here we aimed to create a suitable bony microenvironment with cell-derived ECM and biodegradable ?-tricalcium phosphate (?-TCP). More specifically, we investigated whether the ECM produced by bone marrow-derived mesenchymal stem cells (hBMSC) on a ?-TCP scaffold can bind bone morphogenetic protein-2 (BMP-2) and control its release in a sustained manner, and further examined the effect of ECM and the BMP-2 released from ECM on cell behaviors. The ECM was obtained through culturing the hBMSC on a ?-TCP porous scaffold and performing decellularization and sterilization. SEM, XPS, FTIR, and immunofluorescent staining results indicated the presence of ECM on the ...
Recent studies have shown Y chromosome microdeletions associated with male infertility. The factors responsible for Y chromosome microdeletions in spermatozoa remain unresolved. However, the environmental pollutants are known to damage DNA in differentiating and maturing germ cells in the male reproductive tract. Therefore, the aim of this study was to investigate the effects of seminal hexachlorocyclohexane (HCH) and its isomers, an environmental pollutant, in 50 fertile and 50 infertile males in relation to semen quality and the incidence of Y chromosome microdeletion in azoospermic factor (AZF) region. As compared to control, an increased HCH level and significantly decreased semen quality were observed in the infertile males. A positive significant association was found between sperm c...
Solid state nuclear track detectors (SSNTD) are widely used for radon measurements and CR-39 is one of the most popular SSNTD. In this work it was determined the calibration factor for radon concentration measurements through the passive method with CR-39 detectors. The detectors were put in a proper device (an adapted Lucas cell) and exposed to the standard radon concentration through the Pylon Model RN-150 flow through radon gas source. After exposure, the detectors were etched for 5.5 hours in a KOH solution at 80 deg C in a bath at a constant temperature. The track density was read in an Axiolab-Zeiss optical microscope, with nominal magnification of X10 connected to a video camera and to a personal computer. The calibration factor was obtained through the relation between standard radon concentration, track density and exposure time. (author)
Solid state nuclear track detectors (SSNTD) are widely used for radon measurements and CR-39 is one of the most popular SSNTD. In this work it was determined the calibration factor for radon concentration measurements through the passive method with CR-39 detectors. The detectors were put in a proper device (an adapted Lucas cell) and exposed to the standard radon concentration through the Pylon Model RN-150 flow through radon gas source. After exposure, the detectors were etched for 5.5 hours in a KOH solution at 80 deg C in a bath at a constant temperature. The track density was read in an Axiolab-Zeiss optical microscope, with nominal magnification of X10 connected to a video camera and to a personal computer. The calibration factor was obtained through the relation between standard radon concentration, track density and exposure time. (author)
Individuals with sickle cell disease (SCD) demonstrate an increased susceptibility to invasive bacterial infections (IBI). The most common organisms causing IBI are Streptococcus pneumoniae, nontyphi Salmonella species and Haemophilus influenzae type b (Hib). IBI are the most common causes of death in children below 5 years of age with SCD. Increased susceptibility to IBI is because of several factors including dysfunctional antibody production and opsonophagocytosis as well as defective splenic clearance. Early diagnosis of Hib and pneumococcal infections combined with antibiotic prophylaxis and immunization programs, could lead to significant improvements in mortality, especially in Africa. Pediatr Blood Cancer. 2010;55:401-406. Copyright 2010 Wiley-Liss, Inc.
Investigations of cadmium toxicity to microorganisms are now more concerned with the interactions of cadmium with different environmental factors and other metals. The interactions are complex and have not been thoroughly studied yet. Metal interactions may assume the form of synergism characterized by increase in toxicity, but also of antagonism in which one metal reduces the toxicity of another. Apart from cadmium interactions with such toxic metals as mercury and lead, interactions of cadmium with the essential trace elements seem to be very interesting because it has been assumed that algal cells take up cadmium by the system transporting these elements. A previous study showed that cadmium transport into Stichococcus bacillaris cells was inhibited by Mn/sup 2 +/ ions. Thus, it can be supported that there exist some possibilities of using those ions antagonistic to cadmium as counterposition. Showing those possibilities ...
We present a novel fabrication route yielding Raney-platinum film electrodes intended as glucose oxidation anodes for potentially implantable fuel cells. Fabrication roots on thermal alloying of an extractable metal with bulk platinum at 200^oC for 48h. In contrast to earlier works using carcinogenic nickel, we employ zinc as potentially biocompatible alloying partner. Microstructure analysis indicates that after removal of extractable zinc the porous Raney-platinum film (roughness factor ~2700) consists predominantly of the Pt3Zn phase. Release of zinc during electrode operation can be expected to have no significant effect on physiological normal levels in blood and serum, which promises good biocompatibility. In contrast to previous anodes based on hydrogel-bound catalyst particles the ...
Abstract Host-microorganism interactions in the intestinal tract are complex, and little is known about specific nonpathogenic microbial factors triggering host responses in the gut. In this study, mannose-specific interactions of Lactobacillus plantarum 299v with jejunal epithelium were investigated using an in situ pig Small Intestinal Segment Perfusion model. The effects of L. plantarum 299v wild-type strain were compared with those of two corresponding mutant strains either lacking the gene encoding for the mannose-specific adhesin (msa) or sortase (srtA; responsible for anchoring of cell surface proteins like Msa to the cell wall). A slight enrichment of the wild-type strain associated with the intestinal surface could be observed after 8 h of perfusion when a mixture of wild-type and...
In order to get the separation of natural isotopes of lithium by electrolytic amalgamation, an electrolytic cell with a confined mercury cathode was used to obtain data for the design of a separation stage. The initial work was followed by the design of a moving mercury cathode electrolytic cell and three experiments with six batches stages were performed for the determination of the elementary separation factor. The value obtained, 1.053, was ill agreement: with the specialized literature. It was verified in all experiments that the lithium - 6 isotope concentrated in the amalgam phase and that the lithium - 7 isotope concentrated in the aqueous phase. A stainless-steel cathode for the decomposition of the lithium amalgam and the selective desamalgamation were also studied. In view of the results obtained, a five stages continuous scheme was proposed. (author)
BackgroundPeritoneal metastasis occurs in up to 30% of patients with gastric cancer. The aim of this experimental study is to develop and validate a novel ex vivo model of the human peritoneum to better identify factors involved in the development of peritoneal metastasis in order to improve its management and prognosis. MethodsPeritoneal discs harvested from hernia sacs obtained at inguinal hernia surgery were suspended in media using Teflon rings. Viability of the tissue was investigated using MTS assay, light and scanning electron microscopy (LM and SEM) over 72 h. To assess validity of the model, phenotypic changes in tumor cells were investigated. Changes in matrix metalloproteinases (MMP)-2 and -9 activities in HGC and AGS gastric adenocarcinoma cells after co-culture were investigat...
We hypothesize that the mushroom-derived active compound may be a potential strategy for increasing survival in response to influenza virus (H1N1) infection through the stimulation of host innate immune response. The validity of the hypothesis can be tested by immune response to influenza infection as seen through survival percentage, virus clearance, weight loss, natural killer cell cytotoxicity, Tumor Necrosis Factor-? (TNF-?) and Interferon-gamma (IFN-?) levels, lytic efficiency in the spleens of mice and inducible nitric oxide synthase mRNA expressions in RAW 264.7 murine macrophage cells. The hypothesis may improve people's quality of life, reduce the medical cost of our healthcare system and eliminate people's fears of influenza outbreak. PMID:21660092
In the beginning of 2005 several changes in the electricity and natural gas market law came into effect. This report examines the influence and impact of these changes on the behaviour and development of these markets, looking at the role and position of both the energy industry and customers. The report combines existing data with new research data collected during spring and summer 2006. Whilst the recency of the law changes, along with the simultaneous impact of other market variables limits the salience of any impact, the report nevertheless provides clear and interesting conclusions. In the electricity market, one major legislative change that came into force in the beginning of 2005 concerned the supervision of the reasonableness of electricity distribution pricing. According to the newly adopted ex ante regulation principles, the regulatory authority now determines the guidelines for reasonable pricing prior the start of a predefined regulatory period. So ...
Up to now the retention of radioactive material for nuclear facilities has been based on the maximum individual dose. The maximum individual dose can locally be lowered considerably by higher dissolution. In general, the collective doses are not lowered by this. In order to set up regulations concerning collective doses, the new recommmendations of the ICRP are very welcome. However, the costs of detriment and the period to be considered have not yet been defined. Therefore there are no fixed methods for carrying out a cost-benefit analysis. Furthermore, for nuclear technology the costs and the effectiveness of the retention of radioactive material for non-realized facilities can only be quoted roughly, which makes a cost-benefit analysis more difficult. A cost-benefit analysis for the retention of radioactive material in nuclear power plants with LWRs and reprocessing plants of the PUREX process has been carried out with best estimate data. The results show that ...
The epithermal cross section shielding methods used in the lattice physics code EPRI-CELL (E-C) have been extensively studied to determine its major approximations and to examine the sensitivity of computed results to these approximations. The study has resulted in several improvements in the original methodology. These include: treatment of the external moderator source with intermediate resonance (IR) theory, development of a new Dancoff factor expression to account for clad interactions, development of a new method for treating resonance interference, and application of a generalized least squares method to compute best-estimate values for the Bell factor and group-dependent IR parameters. The modified E-C code with its new ENDF/B-V cross section library is tested for several numerical benchmark problems. Integral parameters computed by EC are compared with those obtained with point-cross section Monte Carlo ...
IMRT with inverse planning allows simultaneous integrated boost strategies that exploit the heterogeneous dose distribution within the planning target volumes (PTVs). In this scenario, the location of cold spots within the target becomes a crucial issue and has to be related to the distribution of the clonogenic cell density (CCD). The main aim of this work is to provide the means to calculate the optimal prescription dose in a relative inhomogeneous dose distribution. To achieve this, the prescription dose has to be assigned to obtain the same tumor control probability (TCP) as the ideal homogeneous distribution, taking into account different CCDs in different PTVs (i.e. visible and subclinical regions). An adapted formulation of the linear-quadratic model, within the F-factor formalism, has been derived to preserve a chosen TCP value for the whole target volume. The F-factor has been investigated to show its potential ...