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The development of high-performance ultraelastic metals with superb strength, a large elastic strain limit and temperature-insensitive elastic modulus (Elinvar effect) are important for various industrial applications, from actuators and medical devices to high-precision instruments1,2. The elastic strain limit of bulk crystalline metals is usually less than 1 per cent, owing to dislocation easy gliding. Shape memory alloys3-including gum metals4,5 and strain glass alloys6,7-may attain an elastic strain limit up to several per cent, although this is the result of pseudo-elasticity and is accompanied by large energy dissipation3. Recently, chemically complex alloys, such as 'high-entropy' alloys8, have attracted tremendous research interest owing to their promising properties9-15. In this work we report on a chemically complex alloy with a large atomic size misfit usually unaffordable in conventional alloys. The alloy exhibits a high elastic strain limit (approximately 2 per cent) and a very low internal friction (less than 2 × 10-4) at room temperature. More interestingly, this alloy exhibits an extraordinary Elinvar effect, maintaining near-constant elastic modulus between room temperature and 627 degrees Celsius (900 kelvin), which is, to our knowledge, unmatched by the existing alloys hitherto reported.
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BACKGROUND: Little is known about the multi-dimensional nature of traumatic duty-related events encountered by firefighters in relation to their post-traumatic stress disorder (PTSD) risk. AIMS: To describe the types of duty-related events encountered by career firefighters and explore if years in the fire service or total event load moderated the association of trauma exposure to PTSD symptoms. METHODS: Participants included 755 career, male firefighters (19% of the department's firefighters and 76% of those who accessed the electronic anonymous survey). The Duty-Related Incident Stressors scale was used to assess exposure to 25 potentially traumatic events (event load) and self-appraisal of the stress associated with these events, grouped by type of event (indirect, direct and colleague-related). The Post-Traumatic Stress Disorder Checklist was used to assess PTSD symptoms. RESULTS: Firefighters rated colleague-related events as the most stressful, followed by indirect and direct events. Event load (râ =â 0.25) and indirect, direct and colleague-related events stress (râ =â 0.32-0.35) were positively associated with PTSD symptoms. Results of moderation analyses indicated that event load served as a risk factor in the relation of indirect events stress to PTSD symptoms, and as a buffer in the relation of direct events stress to PTSD symptoms. Years in the fire service were not associated with PTSD symptoms nor moderated the relation of event stress to PTSD symptoms. CONCLUSIONS: Findings underscored the importance of considering the differential effects that types of duty-related traumatic events and cumulative exposure to trauma may have on firefighters' PTSD symptoms.
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This study investigates the evolution of superconductivity in K2-xFe4+ySe5 using temperature-dependent X-ray absorption and resonant inelastic X-ray scattering techniques. Magnetization measurements show that polycrystalline superconducting (SC) K1.9Fe4.2Se5 has a critical temperature (T c) of â¼31 K with a varying superconducting volume fraction, which strongly depends on its synthesis temperature. An increase in Fe-structural/vacancy disorder in SC samples with more Fe atoms occupying vacant 4d sites is found to be closely related to the decrease in the spin magnetic moment of Fe. Moreover, the nearest-neighbor Fe-Se bond length in SC samples exceeds that in the non-SC (NS) sample, K2Fe4Se5, which indicates a weaker hybridization between the Fe 3d and Se 4p states in SC samples. These results clearly demonstrate the correlations among the local electronic and atomic structures and the magnetic properties of K2-xFe4+ySe5 superconductors, providing deeper insight into the electron pairing mechanisms of superconductivity.
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BACKGROUND: Little is known regarding the mental health of women firefighters. AIMS: To identify demographic, work-related and mental health characteristics associated with post-traumatic stress disorder (PTSD) symptoms and lifetime suicidal ideation in female firefighters compared with male colleagues. METHODS: Participants were firefighters (75 women and 2564 men) employed in a large urban fire department in the USA. Chi-square, correlations, t-tests and analyses of variance were conducted to examine the predictors of PTSD symptoms and lifetime suicide ideation in men and women. RESULTS: Approximately 20% of women scored positively for PTSD and 30% reported lifetime suicidal ideation. Women with PTSD symptoms were more likely to be in their mid-career years (11-20) than in their first 10 years (87% versus 44%; χ2 = 8.77, P < 0.05) and to have received counselling (53% versus 14%; χ2 = 8.11, P < 0.01). Being single (73% versus 58%; χ2 = 6.02, P < 0.05), having a second job (68% versus 38%; χ2 = 5.79, P < 0.05) and having received counselling (41% versus 11%; χ2 = 8.51, P < 0.01) predicted suicide ideation. Depression and general stress positively predicted PTSD symptoms and suicide ideation. PTSD also predicted suicide ideation. CONCLUSIONS: Compared to male firefighters, women were at high risk for PTSD symptoms and suicide ideation. Particularly for women, few socio-demographic and work-related variables were associated with these outcomes. Mental health variables predicted depression and suicide ideation for both gender groups. Therefore, in screening and intervention efforts, it may be most fruitful to focus on mental health risk correlates of PTSD and suicide ideation.
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Bombeiros/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Ideação Suicida , Adulto , Idoso , Depressão/epidemiologia , Feminino , Humanos , Masculino , Estado Civil , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Inquéritos e Questionários , Estados Unidos/epidemiologiaRESUMO
Intermetallic alloys have traditionally been characterized by their inherent brittleness due to their lack of sufficient slip systems and absence of strain hardening. However, here we developed a single-phase B2 high-entropy intermetallic alloy that is both strong and plastic. Unlike conventional intermetallics, this high-entropy alloy features a highly distorted crystalline lattice with complex chemical order, leading to multiple slip systems and high flow stress. In addition, the alloy exhibits a dynamic hardening mechanism triggered by dislocation gliding that preserves its strength across a wide range of temperatures. As a result, this high-entropy intermetallic circumvents precipitous thermal softening, with extensive plastic flows even at high homologous temperatures, outperforming a variety of both body-centered cubic and B2 alloys. These findings reveal a promising direction for the development of intermetallic alloys with broad engineering applications.
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BACKGROUND: We previously reported relatively normal pulmonary function (2 years of age) and computed tomography (CT, 1 year of age) in cystic fibrosis (CF) newborn screened (NBS) infants. We now report follow up of these children to preschool age. METHODS: 67 NBS children with CF and 41 healthy controls underwent pulmonary function tests in infancy (â¼3 months, 1 year and 2 years) and at preschool (3-6 years). Broncho-alveolar lavage (BAL) and CT were undertaken in those with CF at 1 year. Primary outcomes at preschool were lung clearance index (LCI) and forced expired volume (FEV0.75). Risk factors for lung function impairment were identified by regression modelling, emphasising factors that could be identified or measured in the first 2 years of life. RESULTS: At preschool age children with CF had poorer lung function than controls, mean(95% CI) difference in LCI z-score: 1.47(0.96;1.97) and FEV0.75 z-score -0.54(-0.98; -0.10). Isolation of Pseudomonas aeruginosa before 6 months was a highly significant predictor of raised (abnormal) preschool LCI, associated with a mean (95%CI) increase of 1.69(0.43, 2.95) z-scores, compared to those with no Pseudomonas aeruginosa during the first 2 years of life. Including 2 year LCI and 1 year CT data in the predictive model increased the r2 from 13% to 61%. CONCLUSIONS: Lung function deteriorates after 2 years in NBS children with CF. Isolation of Pseudomonas aeruginosa before 6 months and minor abnormalities of infant lung function tests and CT in infancy are associated with higher preschool LCI.
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Fibrose Cística , Lactente , Recém-Nascido , Pré-Escolar , Humanos , Fibrose Cística/complicações , Fibrose Cística/diagnóstico , Pseudomonas aeruginosa , Pulmão/diagnóstico por imagem , Testes de Função Respiratória/métodos , Lavagem BroncoalveolarRESUMO
Temperature-dependent X-ray absorption near-edge structures, X-ray linear dichroism (XLD) and extended X-ray absorption fine structure (EXAFS) spectroscopic techniques were used to investigate the valence state, preferred orbital and local atomic structure that significantly affect the electrical and magnetic properties of a single crystal of YBaCuFeO5 (YBCFO). An onset of increase of resistivity at ~180 K, followed by a rapid increase at/below 125 K, is observed. An antiferromagnetic (AFM)-like transition is close to the temperature at which the resistivity starts to increase in the ab-plane and is also observed with strong anisotropy between the ab-plane and the c-axis. The XLD spectra at the Fe L3,2-edge revealed a change in Fe 3d eg holes from the preferential [Formula: see text] orbital at high temperature (300-150 K) to the [Formula: see text] orbital at/below 125 K. The analysis of the Fe K-edge EXAFS data of YBCFO further revealed an unusual increase in the Debye-Waller factor of the nearest-neighbor Fe-O bond length at/below 125 K, suggesting phonon-softening behavior, resulting in the breaking of lattice symmetry, particularly in the ab-plane of Fe-related square pyramids. These findings demonstrate a close correlation between electrical resistivity and coupling of the preferred Fe 3d orbital with lattice distortion of a single crystal of YBCFO.
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Fe and Y K-edge extended x-ray absorption fine structure, Fe(Y) L(3,2)-edge (L(3)-edge) x-ray absorption near-edge structure (XANES) and valence-band photoemission spectroscopy (VB-PES) measurements have been carried out to study soft magnetic ternary Fe(78-x)Y(x)B(22) bulk metallic glasses (BMGs). The combined XANES and VB-PES results do not show broadening of the Fe 3d band to support the previous interpretation of the reduction of the magnetic moment in BMGs by Y-induced decrease of exchange splitting of Fe 3d orbitals. Instead, the density of delocalized/itinerant Fe 3d states in the vicinity of the Fermi level is found to be reduced by Y substitution, which reduces the strength of itinerant-states-mediated ferromagnetic coupling between local spins on the Fe ions and the total magnetic moment of the Fe-based BMGs.
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This investigation reports on anisotropy in the magnetic interaction, lattice-orbital coupling and degree of phonon softening in single crystal Ni3TeO6 (NTO) using temperature- and polarization-dependent X-ray absorption spectroscopic techniques. The magnetic field-cooled and zero-field-cooled measurements and temperature-dependent Ni L3,2-edge X-ray magnetic circular dichroism spectra of NTO reveal a weak Ni-Ni ferromagnetic interaction close to ~60 K (TSO: temperature of the onset of spin ordering) with a net alignment of Ni spins (the uncompensated components of the Ni moments) along the crystallographic c-axis, which is absent from the ab-plane. Below the Néel temperature, TN~ 52 K, NTO is stable in the antiferromagnetic state with its spin axis parallel to the c-axis. The Ni L3,2-edge X-ray linear dichroism results indicate that above TSO, the Ni 3d eg electrons preferentially occupy the out-of-plane 3d3z2-r2 orbitals and switch to the in-plane 3dx2-y2 orbitals below TSO. The inherent distortion of the NiO6 octahedra and anisotropic nearest-neighbor Ni-O bond lengths between the c-axis and the ab-plane of NTO, followed by anomalous Debye-Waller factors and orbital-lattice in conjunction with spin-phonon couplings, stabilize the occupied out-of-plane (3d3z2-r2) and in-plane (3dx2-y2) Ni eg orbitals above and below TSO, respectively.
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Various synchrotron radiation-based spectroscopic and microscopic techniques are used to elucidate the room-temperature ferromagnetism of carbon-doped ZnO-nanowires (ZnO-C:NW) via a mild C+ ion implantation method. The photoluminescence and magnetic hysteresis loops reveal that the implantation of C reduces the number of intrinsic surface defects and increases the saturated magnetization of ZnO-NW. The interstitial implanted C ions constitute the majority of defects in ZnO-C:NW as confirmed by the X-ray absorption spectroscopic studies. The X-ray magnetic circular dichroism spectra of O and C K-edge respectively indicate there is a reduction in the number of unpaired/dangling O 2p bonds in the surface region of ZnO-C:NW and the C 2p-derived states of the implanted C ions strongly affect the net spin polarization in the surface and bulk regions of ZnO-C:NW. Furthermore, these findings corroborate well with the first-principles calculations of C-implanted ZnO in surface and bulk regions, which highlight the stability of implanted C for the suppression and enhancement of the ferromagnetism of the ZnO-C:NW in the surface region and bulk phase, respectively.
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The calcium-sensing receptor (CaSR) regulates PTH secretion to control the extracellular calcium concentration in adults, but its role in fetal life is unknown. We used CaSR gene knockout mice to investigate the role of the CaSR in regulating fetal calcium metabolism. The normal calcium concentration in fetal blood is raised above the maternal level, an increase that depends upon PTH-related peptide (PTHrP). Heterozygous (+/-) and homozygous (-/-) disruption of the CaSR caused a further increase in the fetal calcium level. This increase was modestly blunted by concomitant disruption of the PTHrP gene and completely reversed by disruption of the PTH/ PTHrP receptor gene. Serum levels of PTH and 1, 25-dihydroxyvitamin D were substantially increased above the normal low fetal levels by disruption of the CaSR. The free deoxypyridinoline level was increased in the amniotic fluid (urine) of CaSR-/- fetuses; this result suggests that fetal bone resorption is increased. Placental calcium transfer was reduced, and renal calcium excretion was increased, by disruption of the CaSR. These studies indicate that the CaSR normally suppresses PTH secretion in the presence of the normal raised (and PTHrP-dependent) fetal calcium level. Disruption of the CaSR causes fetal hyperparathyroidism and hypercalcemia, with additional effects on placental calcium transfer.
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Cálcio/metabolismo , Feto/metabolismo , Troca Materno-Fetal , Hormônio Paratireóideo/metabolismo , Placenta/metabolismo , Proteínas , Receptores de Superfície Celular/metabolismo , Animais , Feminino , Camundongos , Camundongos Knockout , Proteína Relacionada ao Hormônio Paratireóideo , Fragmentos de Peptídeos/metabolismo , Gravidez , Receptores de Detecção de Cálcio , Receptores de Superfície Celular/genéticaRESUMO
X-ray absorption near-edge structure (XANES) and valence-band photoemission spectroscopy (VB-PES) were used to elucidate the electronic and mechanical properties of diamond-like carbon (DLC) thin films deposited by the plasma-enhanced chemical vapour deposition method at various bias voltages (V(b)) using a C(2)H(2) vapour precursor in an Ar(+) atmosphere. The increase of V(b) is found to increase and decrease the contents of sp(3)- and sp(2)-bonded carbon atoms, respectively, i.e. the films become more diamond-like. The Young's modulus measurements show increases with the increase of the presence of sp(3)-bonded carbon atoms in the structure of the DLC films.
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X-ray scattering (XRS), x-ray absorption near-edge structure (XANES) and extended x-ray absorption fine structure (EXAFS) spectroscopic techniques were used to study the electronic and atomic structures of the high-quality Sr3Ir4Sn13 (SIS) single crystal below and above the transition temperature (T* ≈ 147 K). The evolution of a series of modulated satellite peaks below the transition temperature in the XRS experiment indicated the formation of a possible charge density wave (CDW) in the (110) plane. The EXAFS phase derivative analysis supports the CDW-like formation by revealing different bond distances [Sn1(2)-Sn2] below and above T* in the (110) plane. XANES spectra at the Ir L3-edge and Sn K-edge demonstrated an increase (decrease) in the unoccupied (occupied) density of Ir 5d-derived states and a nearly constant density of Sn 5p-derived states at temperatures T < T* in the (110) plane. These observations clearly suggest that the Ir 5d-derived states are closely related to the anomalous resistivity transition. Accordingly, a close relationship exists between local electronic and atomic structures and the CDW-like phase in the SIS single crystal.
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The local electronic and atomic structures of the high-quality single crystal of SrFeO3-δ (δ~0.19) were studied using temperature-dependent x-ray absorption and valence-band photoemission spectroscopy (VB-PES) to investigate the origin of anisotropic resistivity in the ab-plane and along the c-axis close to the region of thermal hysteresis (near temperature for susceptibility maximum, Tm~78 K). All experiments herein were conducted during warming and cooling processes. The Fe L 3,2-edge X-ray linear dichroism results show that during cooling from room temperature to below the transition temperature, the unoccupied Fe 3d e g states remain in persistently out-of-plane 3d 3z2-r2 orbitals. In contrast, in the warming process below the transition temperature, they change from 3d 3z2-r2 to in-plane 3d x2-y2 orbitals. The nearest-neighbor (NN) Fe-O bond lengths also exhibit anisotropic behavior in the ab-plane and along the c-axis below Tm. The anisotropic NN Fe-O bond lengths and Debye-Waller factors stabilize the in-plane Fe 3d x2-y2 and out-of-plane 3d 3z2-r2 orbitals during warming and cooling, respectively. Additionally, a VB-PES study further confirms that a relative band gap opens at low temperature in both the ab-plane and along the c-axis, providing the clear evidence of the charge-density-wave nature of SrFeO3-δ (δ~0.19) single crystal.
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The insulin-like growth factors (IGFs) have diverse anabolic cellular functions, and structure similar to that of proinsulin. The distribution of IGFs and their receptors in a wide variety of organs and tissues enables the IGFs to exert endocrine, paracrine, and autocrine effects on cell proliferation and differentiation, caloric storage, and skeletal elongation. IGF-I exhibits particular metabolic responsiveness, and circulating IGF-I originates predominantly in the liver. Hepatic IGF-I production is controlled at the level of gene transcription, and transcripts are initiated largely in exon 1. Hepatic IGF-I gene transcription is reduced in conditions of protein malnutrition and diabetes mellitus, and our laboratory has used in vitro transcription to study mechanisms related to diabetes. We find that the presence of sequences downstream from the major transcription initiation sites in exon 1 is necessary for the diabetes-induced decrease in IGF-I transcription. Six nuclear factor binding sites have been identified within the exon 1 downstream region, and footprint sites III and V appear to be necessary for metabolic regulation; region V probes exhibit a decrease in nuclear factor binding with hepatic nuclear extracts from diabetic animals. IGFs in biological fluids are associated with IGF binding proteins, and IGFs circulate as a 150-kDa complex that consists of an IGF, an IGFBP-3, and an acid-labile subunit. Circulating IGFBP-3 originates mainly in hepatic nonparenchymal cells, where IGF-I increases IGFBP-3 mRNA stability, but insulin increases IGFBP-3 gene transcription. Regulation of IGFBP-3 gene transcription by insulin appears to be mediated by an insulin-responsive element, which recognizes insulin-responsive nuclear factors in both gel mobility shift assays and southwestern blots. Studies of mechanisms underlying the modulation of IGF-I and IGFBP-3 gene transcription, and identification of critical nuclear proteins involved, should lead to new understanding of the role and regulation of these important growth factors in diabetes mellitus and other metabolic disorders.
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Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Animais , Sequência de Bases , Sítios de Ligação , DNA/genética , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Regulação da Expressão Gênica , Humanos , Insulina/deficiência , Dados de Sequência Molecular , Estado NutricionalRESUMO
During development of the visual system of the ferret, the terminals of retinal ganglion cell axons first segregate to form eye-specific layers and subsequently On-center and Off-center sublayers within the dorsal lateral geniculate nucleus (dLGN). Sublamination requires the activity of the afferent fibers, NMDA receptors, and nitric oxide synthase (NOS). We here report that soluble guanylyl cyclase (sGC), which in turn produces cGMP, is critically involved in the process of sublamination. cGMP expression is upregulated in both retinal terminals and postsynaptic dLGN cells during sublamination, and this expression is controlled by the activity of both NMDA receptors and NOS. Furthermore, the infusion of specific inhibitors of sGC or protein kinase G (PKG), a target of cGMP, prevents sublamination in vivo. We conclude that the sGC-cGMP-PKG pathway acts downstream of NMDA receptors and nitric oxide as an effector of the activity-dependent refinement of connections at this level of the mammalian visual system.
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Carbazóis , GMP Cíclico/metabolismo , Corpos Geniculados/efeitos dos fármacos , Guanilato Ciclase/antagonistas & inibidores , Indóis , Células Ganglionares da Retina/efeitos dos fármacos , Envelhecimento/metabolismo , Alcaloides/farmacologia , Animais , Proteínas Quinases Dependentes de GMP Cíclico/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Furões , Corpos Geniculados/citologia , Corpos Geniculados/metabolismo , Guanilato Ciclase/metabolismo , Técnicas In Vitro , Neurópilo/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Oxidiazóis/farmacologia , Terminações Pré-Sinápticas/metabolismo , Terminações Pré-Sinápticas/ultraestrutura , Quinoxalinas/farmacologia , Receptores de N-Metil-D-Aspartato/metabolismo , Células Ganglionares da Retina/citologia , Células Ganglionares da Retina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Sinaptofisina/metabolismoRESUMO
The accumulation of low molecular weight RNAs in Escherichia coli cells following amino acid or energy source starvation was examined using two-dimensional polyacrylamide gel electrophoresis. 32P-labeled small RNA prepared from serine- or isoleucine-starved stringent strain (relA+) cells was shown to display gel patterns that were grossly different from that of unstarved cells. It appears that the deprivation of serine or isoleucine has little or no inhibitory effect on the accumulation of transfer RNA cognate to the deprived amino acid. This is demonstrated by a relative increase in the concentrations of small RNAs that can be charged with serine or isoleucine following starvation of these amino acids. However, small RNAs labeled during starvation of phenylalanine or energy source showed gel patterns similar to that of control cells. This suggested a heterogenous response in the accumulation of some low molecular weight RNAs, presumably transfer RNAs, following starvation of different amino acids.
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Aminoácidos/farmacologia , Escherichia coli/metabolismo , RNA Bacteriano/metabolismo , RNA de Transferência/metabolismo , Eletroforese em Gel de Poliacrilamida , Metabolismo Energético , Isoleucina/deficiência , Peso Molecular , Fenilalanina/deficiência , RNA Bacteriano/isolamento & purificação , RNA de Transferência/isolamento & purificação , Serina/deficiênciaRESUMO
Unusual guanosine nucleotides guanosine 5'-diphosphate 3'-diphosphate (ppGpp, also known as MSI) and guanosine 5'-diphosphate 3'-monophosphate (ppGp, also known as MSIII) accumulate to high concentrations in wild-type cells of Escherichia coli during amino acid starvation. We reported here that both nucleotides strongly inhibit the activity of enzymes IMP dehydrogenase and adenylosuccinate synthetase, the first enzymes of the guanylate and adenylate biosynthetic pathways. In both cases, ppGP (MSII) is a stronger inhibitor than ppGpp (MSI). On the other hand, these two nucleotides exhibited opposite effects on the activity of phosphoenolpyruvate carboxylase, the enzyme that utilizes phosphoenolpyruvate. At their respective physiological concentrations, the activity of phosphoenolpyruvate carboxylase is activated by ppGpp and inhibited by ppGp.
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Escherichia coli/enzimologia , Nucleotídeos de Guanina/farmacologia , Guanosina Tetrafosfato/farmacologia , Adenilossuccinato Sintase/antagonistas & inibidores , Ativação Enzimática , Guanosina Difosfato/farmacologia , Guanosina Trifosfato/farmacologia , IMP Desidrogenase/antagonistas & inibidores , Fosfoenolpiruvato Carboxilase/metabolismoRESUMO
PURPOSE: To determine the presence of cervical cancer cells in circulating peripheral blood of stage IVb cervical cancer patients with metastasis to distant organs. PATIENTS AND METHODS: Cervical cancer tissue from 15 stage IVb cervical cancer patients with metastasis were analyzed for the presence of human papillomavirus (HPV) type 16 DNA by nested polymerase chain reaction (PCR). The presence of transcriptional products of the HPV type 16 E6-transforming gene in the peripheral blood of the same 15 cancer patients was analyzed by reverse transcription and PCR. Cervical tissues and peripheral-blood specimens from 12 normal healthy individuals served as controls. RESULTS: Thirteen of 15 (86.7%) cervical cancer tissues from same number of patients were found to contain HPV type 16 DNA. Peripheral-blood specimens from 12 of 13 (92.3%) cervical HPV DNA-positive patients were found to contain HPV-specific mRNA detectable by reverse transcription (RT) and PCR. Cervical tissues from all 12 normal controls were HPV-free. None of the peripheral-blood specimens from two cervical HPV-negative cancer patients and 12 normal controls contained detectable amounts of mRNA of HPV type 16 E6-transforming gene. CONCLUSION: The most likely source of the HPV-specific mRNA detected in the peripheral blood of cervical cancer patients with metastasis is the cervical cancer cells derived from or shed from the cervix. The presence of HPV E6 mRNAs in peripheral blood may be a sensitive indicator of circulating cervical cancer cells. If PCR positivity is proven to be able to predict disease progression reliably, these findings may have clinical applications in the treatment of cervical and many other cancers.