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The ternary AMnBi_{2} (A is alkaline as well as rare-earth atom) materials provide an arena for investigating the interplay between low-dimensional magnetism of the antiferromagnetic MnBi layers and the electronic states in the intercalated Bi layers, which harbor relativistic fermions. Here, we report on a comprehensive study of the optical properties and magnetic torque response of Ca_{1-x}Na_{x}MnBi_{2}. Our findings give evidence for a spin canting occurring at T_{s}â¼50-100 K. With the support of first-principles calculations we establish a direct link between the spin canting and the reconstruction of the electronic band structure, having immediate implications for the spectral weight reshuffling in the optical response, signaling a partial gapping of the Fermi surface, and the dc transport properties below T_{s}.
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Objective: To investigate the effects and the underlying mechanism of DS2, a newly synthetic analog of natural ent-kaurane diterpenoid, on the proliferation and migration capabilities of human gastric cancer cells. Methods: MTT assay, colony formation assay and flow cytometry were used to measure the effects of DS2 on growth, apoptosis and cell cycle of several human gastric cancer cell lines. The function of DS2 in the migration was further detected by wound healing and transwell assays. The expression of migration related proteins were determined by western blot. Results: DS2 inhibited the growth of MGC-803, SGC-7901 and HGC-27 cells in a dose dependent manner. After treatment of DS2 at a concentration of 6.25 µmol/L for 24 h, the survival rates of MGC-803, SGC-7901 and HGC-27 cells were 53.87±3.05%, 55.91±6.97% and 32.41±2.64%, respectively. However, for the normal gastric epithelial cell GES-1, no obvious growth inhibition was observed. In addition, DS2 caused significant G(2)/M arrest and induced apoptosis in MGC-803 cells. Furthermore, compared with the negative control, the colony formation, wound healing rate as well as the number of migrating cells of MGC-803 were significantly decreased in a dose dependent manner after DS2 treatment. DS2 induced the expression of E-cadherin, whereas ß-catenin and N-cadherin levels were downregulated in MGC-803. Conclusion: The new compound DS2 has a strong anti-cancer activity, and this study will help us to design and synthesize better diterpenoids derivatives.
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Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Diterpenos de Tipo Kaurano/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Apoptosis , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular , Diterpenos de Tipo Kaurano/química , Regulación hacia Abajo , Humanos , Neoplasias Gástricas/patología , Ensayo de Tumor de Célula MadreRESUMEN
Objective: To investigate the effects of hepcidin on iron, osteoclasts and bone mass in iron accumulation mice. Methods: Eight-week old C57/BL6 male mice were divided into control group (CTR group), high iron group (Fe group) and iron reduction group (Hepc group). CTR group and Fe group were wild-type mice, Hepc group were hepcidin gene overexpression mice.Fe group and Hepc group were injected intraperitoneally with iron, and the mice in the CTR group were injected intraperitoneally with the same amount of saline.Three groups of mice were injected with tamoxifen to induce hepcidin overexpression.Eight weeks later, specimens of three groups of mice were collected and the serum levels of hepcidin, ferritin and carboxy-terminal telopeptides (CTX) were measured by enzyme linked immunosorbent assay (ELISA). Frozen section and Prussian blue stain were carried out to detect bone iron.Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect osteoclast related gene expression[cytokinin (CTK), matrix metalloprotein (MMP9), protein tyrosine kinase 2ß(PTK2ß), cathepsin K (CTSK)]. Tartrate resistant acid phosphatase (TRAP) staining was used to observe the proliferation and differentiation of osteoclasts.The osteoclast activity was examined by lacunar resorption pits.The microstructure of the femur was measured by micro-computed tomography (Micro-CT). Variance analysis was applied to compare the differences among groups. Results: The levels of serum hepcidin in CTR, Fe and Hepc group were (508±42), (728±82) and (1 423±85) ng/L, respectively; serum ferritin were (355±26), (1 270±35) and (801±23) µg/L, respectively; CTX were (4.4±0.5), (13.9±1.4) and (8.5±0.6) mg/L, respectively; there were significant differences in the up-mentioned indexes among the three groups (F=129.6, 781.7, 77.3, all P<0.05). The genes expression level of CTK, MMP9, PTK2ß, TRAP, CTSK in the Hepc and CTR group were all significantly lower than those in Fe group (F=39.6, 8.0, 5.4, 19.5, 8.8, all P<0.05). The results of TRAP staining and pits formation also showed that osteoclast proliferation and activity in group Hepc reduced significantly when compared with those in Fe group (t=4.295, 7.557, both P<0.05). Conclusion: The overexpression of hepcidin can down-regulate the content of ferritin in iron-accumulating mice and inhibit the proliferation, differentiation and activity of osteoclasts, and improve the bone mass.
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Osteoclastos , Animales , Resorción Ósea , Hepcidinas , Hierro , Masculino , Ratones , Fosfatasa Ácida Tartratorresistente , Microtomografía por Rayos XRESUMEN
Here, we experimentally study the origin of d-electron heavy fermion (HF) behavior in iron-based superconductors (FeSCs) AFe_{2}As_{2} (A=K, Rb, Cs). Nuclear magnetic resonance on ^{75}As reveals a universal coherent-incoherent crossover with a characteristic temperature T^{*}. Below T^{*}, a so-called "Knight shift anomaly" is first observed in FeSCs, which exhibits a scaling behavior similar to f-electron HF materials. Furthermore, the scaling rule also regulates the manifestation of magnetic fluctuation. These results undoubtedly support an emergent Kondo lattice scenario for the d-electron HF behavior, which qualifies the AFe_{2}As_{2} (A=K, Rb, Cs) as d-electron HF superconductors.
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The intertwining between spin, charge, and lattice degrees of freedom can give rise to unusual macroscopic quantum states, including high-temperature superconductivity and quantum anomalous Hall effects. Recently, a charge density wave (CDW) has been observed in the kagome antiferromagnet FeGe, indicative of possible intertwining physics. An outstanding question is that whether magnetic correlation is fundamental for the spontaneous spatial symmetry breaking orders. Here, utilizing elastic and high-resolution inelastic x-ray scattering, we observe a c-axis superlattice vector that coexists with the 2[Formula: see text]2[Formula: see text]1 CDW vectors in the kagome plane. Most interestingly, between the magnetic and CDW transition temperatures, the phonon dynamical structure factor shows a giant phonon-energy hardening and a substantial phonon linewidth broadening near the c-axis wavevectors, both signaling the spin-phonon coupling. By first principles and model calculations, we show that both the static spin polarization and dynamic spin excitations intertwine with the phonon to drive the spatial symmetry breaking in FeGe.
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We systematically investigated the in-plane resistivity anisotropy of electron-underdoped EuFe(2-x)Co(x)As(2) and BaFe(2-x)Co(x)As(2) and hole-underdoped Ba(1-x)K(x)Fe(2)As(2). Large in-plane resistivity anisotropy was found in the former samples, while tiny in-plane resistivity anisotropy was detected in the latter ones. When it is detected, the anisotropy starts above the structural transition temperature and increases smoothly through it. As the temperature is lowered further, the anisotropy takes a dramatic enhancement through the magnetic transition temperature. We found that the anisotropy is universally tied to the presence of T-linear behavior of resistivity. Our results demonstrate that the nematic state is caused by electronic degrees of freedom, and the microscopic orbital involvement in the magnetically ordered state must be fundamentally different between the hole- and electron-doped materials.
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We study the normal-state transport properties of AFe2As2 (A = K, Rb and Cs) single crystals using Hall coefficient, resistivity and magnetoresistance (MR) measurements. In all three materials, the Hall coefficient R H shows a strong temperature dependence, which is typical for multi-band systems. In particular, R H develops an upturn below a characteristic temperature [Formula: see text], which is in agreement with the incoherence-coherence crossover reported in recent nuclear magnetic resonance studies. A Fermi-liquid-like state, characterized by T (2) behavior of the resistivity and a positive orbital MR obeying Kohler's rule, emerges below T FL â¼0.4 [Formula: see text]. The superconducting transition temperature T c experiences a simultaneous suppression with [Formula: see text] and T FL as the alkali ion's radius increases from A = K to A = Cs, suggesting that the unconventional superconductivity in the AFe2As2 series is related to the strength of the electronic coherence. A phase diagram, similar to that in the heavy fermion Kondo lattice system, is obtained. Based on all the experimental evidence, we argue that the physical properties of this family of heavily hole-doped Fe-based superconductors are controlled by the hybridization between itinerant carriers and localized orbitals, and the Kondo scenario could be effective in such a case.
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The 2.5 A crystal structures of the DNA-binding domain of the E2 protein from bovine papillomavirus strain 1 and its complex with DNA are presented. E2 is a transcriptional regulatory protein that is also involved in viral DNA replication. It is the structural prototype for a novel class of DNA-binding proteins: dimeric beta-barrels with surface alpha-helices that serve as recognition helices. These helices contain the amino-acid residues involved in sequence-specifying interactions. The E2 proteins from different papillomavirus strains recognize and bind to the same consensus 12 base-pair DNA sequence. However, recent evidence from solution studies points to differences in the mechanisms by which E2 from the related viral strains bovine papillomavirus-1 and human papillomavirus-16 discriminate between DNA targets based on non-contacted nucleotide sequences. This report provides evidence that sequence-specific DNA-binding is accompanied by a rearrangement of protein subunits and deformation of the DNA. These results suggest that, along with DNA sequence-dependent conformational properties, protein subunit orientation plays a significant role in the mechanisms of target selection utilized by E2.
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Papillomavirus Bovino 1/metabolismo , ADN Viral/metabolismo , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/metabolismo , Proteínas Virales/química , Proteínas Virales/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Sitios de Unión/genética , Papillomavirus Bovino 1/química , Papillomavirus Bovino 1/genética , Bovinos , Cristalografía por Rayos X , ADN Viral/genética , Proteínas de Unión al ADN/genética , Dimerización , Humanos , Sustancias Macromoleculares , Modelos Moleculares , Datos de Secuencia Molecular , Conformación de Ácido Nucleico , Proteínas Oncogénicas Virales/química , Proteínas Oncogénicas Virales/metabolismo , Unión Proteica , Conformación Proteica , Estructura Secundaria de Proteína , Proteínas Virales/genéticaRESUMEN
Tremendous efforts towards improvement in the critical current density "Jc" of iron based superconductors (FeSCs), especially at relatively low temperatures and magnetic fields, have been made so far through different methods, resulting in real progress. Jc at high temperatures in high fields still needs to be further improved, however, in order to meet the requirements of practical applications. Here, we demonstrate a simple approach to achieve this. Hydrostatic pressure can significantly enhance Jc in NaFe0.97Co0.03As single crystals by at least tenfold at low field and more than a hundredfold at high fields. Significant enhancement in the in-field performance of NaFe0.97Co0.03As single crystal in terms of pinning force density (Fp) is found at high pressures. At high fields, the Fp is over 20 and 80 times higher than under ambient pressure at12 K and 14 K, respectively, at P = 1 GPa. We believe that the Co-doped NaFeAs compounds are very exciting and deserve to be more intensively investigated. Finally, it is worthwhile to say that by using hydrostatic pressure, we can achieve more milestones in terms of high Jc values in tapes, wires or films of other Fe-based superconductors.
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NaFe2As2 is investigated experimentally using powder x-ray diffraction and Raman spectroscopy at pressures up to 23 GPa at room temperature and using ab-initio calculations. The results reveal a pressure-induced structural modification at 4 GPa from the starting tetragonal to a collapsed tetragonal phase. We determined the changes in interatomic distances under pressure that allowed us to connect the structural changes and superconductivity. The transition is related to the formation of interlayer As-As bonds at the expense of weakening of Fe-As bonds in agreement with recent theoretical predictions.
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The administration of morphine and fentanyl by continuous intravenous infusion has been shown to produce analgesic tolerance and physical dependence in human neonates. In animals, daily repeated morphine bolus injections is a common method of inducing neonatal rat tolerance and dependence. Yet this method differs from the intravenous route reported to affect human neonates. Alzet osmotic minipumps were implanted in postnatal day 14 rats to provide a continuous morphine infusion more closely mimicking the clinical picture. Rats remained naive or were infused with saline or morphine (0.7 mg/kg/h) for 72 h. Morphine's antinociceptive potency was similar between naive and saline-infused animals, while morphine-infused animals were tolerant. Gender did not contribute to the degree of tolerance observed. Naloxone precipitated withdrawal in the morphine pump-implanted rats was similar to that reported by others. Thus, minipumps provide a useful model for assessing the tolerance and dependence liability of different opioids.
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Analgésicos Opioides/farmacología , Animales Recién Nacidos/fisiología , Dependencia de Morfina/psicología , Morfina/farmacología , Animales , Implantes de Medicamentos , Tolerancia a Medicamentos , Femenino , Masculino , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Ratas , Ratas Sprague-Dawley , Tiempo de Reacción/efectos de los fármacos , Factores Sexuales , Síndrome de Abstinencia a Sustancias/psicologíaRESUMEN
We successfully synthesized La- and Sm-doped phenanthrene powder samples and observed superconductivity in them at T(c) around 6 K. The T(c)s are 6.1 K for La(1) phenanthrene and 6.0 K for Sm(1) phenanthrene, which are enhanced by about 1 and 0.5 K compared to those in A(3) phenanthrene (A = K and Rb) and in Ae(1.5) phenanthrene (Ae = Sr and Ba) superconductors, respectively. The superconductive shielding fractions for La(1) phenanthrene and Sm(1) phenanthrene are 46.1% and 49.8% at 2 K, respectively. The small effect of doping with the magnetic ion Sm(3+) on T(c) and the positive pressure dependence coefficient of T(c) strongly suggest unconventional superconductivity in the doped phenanthrene superconductors. The charge transfer to organic molecules from dopants of La and Sm induces a redshift of 7 cm(-1) per electron for the mode at 1441 cm(-1) in the Raman spectra, which is almost the same as those observed in A(3) phenanthrene (A = K and Rb) and Ae(1.5) phenanthrene (Ae = Sr and Ba) superconductors.
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A reliable and reproducible method, capillary zone electrophoresis with amperometric detection (CZE-AD), has been developed for separation and quantification of levodopa methyl ester (LDME) and its biotransformation products levodopa (L-DOPA) and dopamine (DA) in rat serum. A carbon-disk electrode was used as working electrode. The optimum conditions for CZE detection were 50 mmol L(-1) phosphate solution at pH 7.0 as running buffer, 17 kV as separation voltage, 1.0 V (vs Ag/AgCl, 3.0 mol L(-1)) as detection potential, and sample injection for 8 s at 17 kV. The linear ranges were from 2.4 x 10(-2) to 2.2 microg mL(-1) for LDME, 2.9 x 10(-1) to 49.5 microg mL(-1) for L-DOPA, and 1.4 x 10(-2) to 1.5 microg mL(-1) for DA with correlation coefficients of 0.9997, 0.9994, and 0.9999, respectively. The detection limits for LDME, L-DOPA, and DA were 14.6, 98.0, and 9.7 ng mL(-1), respectively. Recoveries were 80.3% for LDME, 93.5% for L-DOPA, and 86.5% for DA. This method was applied to serum samples after intravenous injection of LDME and L-DOPA to rats.
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Electroquímica/métodos , Electroforesis Capilar/métodos , Levodopa/análogos & derivados , Animales , Biotransformación , Tampones (Química) , Concentración de Iones de Hidrógeno , Levodopa/sangre , Levodopa/farmacocinética , Masculino , Ratas , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
The papillomavirus E2 proteins regulate the transcription of all papillomavirus genes and are necessary for viral DNA replication. Disruption of the E2 gene is commonly associated with malignancy in cervical carcinoma, indicating that E2 has a role in regulating tumor progression. Although the E2 proteins from all characterized papillomaviruses bind specifically to the same 12-base pair DNA sequence, the cancer-associated human papillomavirus E2 proteins display a unique ability to detect DNA flexibility and intrinsic curvature. To understand the structural basis for this phenomenon, we have determined the crystal structures of the human papillomavirus-18 E2 DNA-binding domain and its complexes with high and low affinity binding sites. The E2 protein is a dimeric beta-barrel and the E2-DNA interaction is accompanied by a large deformation of the DNA as it conforms to the E2 surface. DNA conformation and E2-DNA contacts are similar in both high and low affinity complexes. The differences in affinity correlate with the flexibility of the DNA sequence. Preferences of E2 proteins from different papillomavirus strains for flexible or prevent DNA targets correlate with the distribution of positive charge on their DNA interaction surfaces, suggesting a role for electrostatic forces in the recognition of DNA deformability.
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ADN/química , Conformación de Ácido Nucleico , Proteínas Oncogénicas Virales/metabolismo , Secuencia de Aminoácidos , Secuencia de Bases , Sitios de Unión , ADN/metabolismo , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/metabolismo , Escherichia coli/metabolismo , Cinética , Modelos Genéticos , Modelos Moleculares , Datos de Secuencia Molecular , Proteínas Oncogénicas Virales/química , Unión Proteica , Conformación Proteica , Estructura Terciaria de Proteína , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido Nucleico , Estereoisomerismo , Proteínas Virales/química , Proteínas Virales/metabolismoRESUMEN
To test the inducibility of CYP1A homologs in guinea pig adrenal, the effects of 3,3'-methylcholanthrene, an archetypal inducer of CYP1A, were compared in guinea pig adrenal and liver. Western blot analysis showed that levels of both CYP1A1 (53 kDa) and CYP1A2 (56 kDa) increasedin liver microsomes of 3,3'-methylcholanthrene-treated guinea pigs. In adrenals, an immunoreactive protein comigrating with liver CYP1A1 was detected only after 3,3'-methylcholanthrene treatment. Protein comigrating with CYP1A2 was never detected in adrenal microsomes. A third inducible immunoreactive protein (57 kDa) was seen in liver, but not adrenal, after 3, 3'-methylcholanthrene treatment. Another immunoreactive protein (52 kDa), present constitutively in liver and adrenal microsomes, was not induced in either tissue by 3,3'-methylcholanthrene. The precise identities of the inducible 57-kDa and the noninducible 52-kDa proteins remain to be determined. However, the identity of the 53-kDa protein in the adrenal as CYP1A1 was confirmed by RT-PCR, Northern blot, and sequence analysis. Similar analyses demonstrated that, despite the fact that the 56-kDa protein was not detectable in adrenal microsomes, CYP1A2 mRNA was present in adrenals of control animals. Strikingly, CYP1A2 mRNA decreased in adrenal, but increased in liver, following 3,3'-methylcholanthrene treatment, underscoring differences in the regulation of CYP1A expression in the two tissues. Levels of ethoxyresorufin and methyoxyresorufin metabolism correlated with levels of CYP1A1 and CYP1A2 protein, respectively.
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Glándulas Suprarrenales/metabolismo , Citocromo P-450 CYP1A1/biosíntesis , Citocromo P-450 CYP1A2/biosíntesis , Metilcolantreno/farmacología , Glándulas Suprarrenales/efectos de los fármacos , Animales , Northern Blotting , Western Blotting , Inducción Enzimática/efectos de los fármacos , Cobayas , Humanos , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Reacción en Cadena de la Polimerasa , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
The vertebrate lens is a relatively simple cellular structure that has evolved to refract light. The ability of the lens to focus light on the retina derives from a number of properties including the expression at high levels of a selection of soluble proteins referred to as the crystallins. In the present study, we have used differential cDNA display techniques to identify a novel, highly abundant and soluble lens protein. Though related to the family of soluble lectins called galectins, it does not bind beta-galactoside sugars and has atypical sequences at normally conserved regions of the carbohydrate-binding domain. Like some galectin family members, it can form a stable dimer. It is expressed only in the lens and is located at the interface between lens fiber cells despite the apparent lack of any membrane-targeting motifs. This protein is designated GRIFIN (galectin-related inter-fiber protein) to reflect its exclusion from the galectin family given the lack of affinity for beta-galactosides. Although the abundance, solubility, and lens-specific expression of GRIFIN would argue that it represents a new crystallin, its location at the fiber cell interface might suggest that its primary function is executed at the membrane.