RESUMEN
The electronic structure and transport properties of monatomic Fe wires of different characteristics are studied within the density functional theory. In both equidistant and dimerized (more stable) isolated wires, magnetism plays an important role since it leads to different shapes of the transmission coefficients for each spin component. In equidistant wires, electron localization around the Fermi level leads to symmetry breaking between d(xy) and d(x(2)-y(2)) bands. The main effect of the structural dimerization is to decrease the number of channels available for the minority spin component. When anchored to the edges of a graphene nanoribbon, the dimerization of the chain is preserved, despite the hybridization of the d states of Fe with the C atoms which gives way to a reduction in the number of d channels around the Fermi level. Most conduction is then led by an electronic channel from the ribbon and the sp(z) bands from the Fe wires. Suggestions to improve the spintronic ability of Fe wires are proposed.
RESUMEN
A new three-body method is used to compute the rate of the triple-alpha capture reaction, which is the primary source of 12C in stars. In this Letter, we combine the Faddeev hyperspherical harmonics and the R-matrix method to obtain a full solution to the three-body α+α+α continuum. Particular attention is paid to the long-range effects caused by the pairwise Coulomb interactions. The new rate agrees with the Nuclear Astrophysics Compilation of Reaction rates for temperatures greater than 0.07 GK, but a large enhancement at lower temperature is found (≈10(12) at 0.02 GK). Our results are compared to previous calculations where additional approximations were made. We show that the new rate does not significantly change the evolution of stars around one solar mass. In particular, such stars still undergo a red-giant phase consistent with observations, and no significant differences are found in the final white dwarfs.
RESUMEN
The dissociation of iron from heme is a major factor in iron metabolism and the cellular concentrations of the metal correlate with heme degradation. We tested the hypotheses that (1) exposure to a product of heme catabolism, carbon monoxide (CO), alters iron homeostasis in the lung and in cultured respiratory epithelial cells; (2) this response includes both decreased uptake and increased release of cell metal; and (3) the effects of CO on cell function track changes in metal homeostasis. In rats exposed to 50 ppm CO for 24 hours, non-heme iron concentrations decreased in the lung and increased in the liver. In respiratory epithelial cells cultured at air-liquid interface, CO exposure decreased cell non-heme iron and ferritin concentrations within 2 hours and the effect was fully reversible. CO significantly depressed iron uptake by epithelial cells, despite increased expression of divalent metal transporter-1, while iron release was elevated. The loss of non-heme iron after CO reduced cellular oxidative stress, blocked the release of the proinflammatory mediator (interleukin-8), and interfered with cell cycle protein expression. We conclude that CO reduces the iron content of the lung through both the metal uptake and release mechanisms. This loss of cellular iron after CO is in line with certain biological effects of the gas that have been implicated in the protection of cell viability.
Asunto(s)
Antimetabolitos/farmacología , Monóxido de Carbono/farmacología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Homeostasis , Hierro/metabolismo , Mucosa Respiratoria , Acetaldehído/metabolismo , Animales , Antimetabolitos/metabolismo , Antioxidantes/metabolismo , Lavado Broncoalveolar , Monóxido de Carbono/metabolismo , Línea Celular , Proliferación Celular , Niño , Deferoxamina/metabolismo , Células Epiteliales/citología , Ferritinas/metabolismo , Hemo/química , Hemo/metabolismo , Humanos , Interleucina-8/metabolismo , Masculino , Estrés Oxidativo , Ratas , Ratas Sprague-Dawley , Mucosa Respiratoria/citología , Mucosa Respiratoria/efectos de los fármacos , Sideróforos/metabolismoRESUMEN
Mast cell numbers are significantly increased in bladder disorders including malignancy and interstitial cystitis, but their precise role has been difficult to determine. We characterized the role of mast cells on gene regulation associated with antigen-induced bladder inflammation in mice. For this purpose, we examined the responses in mast cell-deficient (Kit(W)/Kit(W-v)), congenic normal (+/+), and Kit(W)/Kit(W-v) mice that were reconstituted with bone marrow stem cells (BMR) to restore mast cells. All mice were actively sensitized and challenged intravesically with either saline or specific antigen. Bladder inflammation occurred in +/+ and BMR but not the Kit(W)/Kit(W-v) mice. Gene expression was determined using mouse cDNA expression arrays. Self-organizing maps, performed without preconditions, indicated gene expression changes dependent on the presence of mast cells. These genes were upregulated in bladders isolated from antigen challenge of +/+, not altered in Kit(W)/Kit(W-v), and were upregulated in BMR mice. Taken together these results demonstrate an important role for mast cells in allergic cystitis and indicate that mast cells can alter their environment by regulating tissue gene expression.
Asunto(s)
Antígenos/inmunología , Cistitis/inmunología , Cistitis/metabolismo , Perfilación de la Expresión Génica , Mastocitos/inmunología , Vejiga Urinaria/inmunología , Vejiga Urinaria/patología , 2,4-Dinitrofenol/inmunología , Enfermedad Aguda , Animales , Trasplante de Médula Ósea , Análisis por Conglomerados , Cistitis/patología , ADN Complementario/genética , Femenino , Regulación de la Expresión Génica , Humanos , Inmunoglobulina E/inmunología , Inflamación/inmunología , Inflamación/metabolismo , Inflamación/patología , Mastocitos/trasplante , Ratones , Ratones Congénicos , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/fisiología , Albúmina Sérica/inmunología , Vejiga Urinaria/metabolismoRESUMEN
In this study, self-organizing map (SOM) gene cluster techniques are applied to the analysis of cDNA microarray analysis of gene expression changes occurring in the early stages of genitourinary inflammation. We determined the time course of lipopolysaccharide (LPS)-induced gene expression in experimental cystitis. Mice were euthanized 0.5, 1, 4, and 24 h after LPS instillation into the urinary bladder, and gene expression was determined using four replicate Atlas mouse cDNA expression arrays containing 588 known genes at each time point. SOM gene cluster analysis, performed without preconditions, identified functionally significant gene clusters based on the kinetics of change in gene expression. Genes were classified as follows: 1) expressed at time 0; 2) early genes (peak expression between 0.5 and 1 h); and 3) late genes (peak expression between 4 and 24 h). One gene cluster maintained a constant level of expression during the entire time period studied. In contrast, LPS treatment downregulated the expression of some genes expressed at time 0, in a cluster including transcription factors, protooncogenes, apoptosis-related proteins (cysteine protease), intracellular kinases, and growth factors. Gene upregulation in response to LPS was observed as early as 0.5 h in a cluster including the interleukin-6 (IL-6) receptor, alpha- and beta-nerve growth factor (alpha- and beta-NGF), vascular endothelial growth factor receptor-1 (VEGF R1), C-C chemokine receptor, and P-selectin. Another tight cluster of genes with marked expression at 1 h after LPS and insignificant expression at all other time points studied included the protooncogenes c-Fos, Fos-B, Fra-2, Jun-B, Jun-D, and Egr-1. Almost all interleukin genes were upregulated as early as 1 h after stimulation with LPS. Nuclear factor-kappaB (NF-kappaB) pathway genes collected in a single cluster with a peak expression 4 h after LPS stimulation. In contrast, most of the interleukin receptors and chemokine receptors presented a late peak of expression 24 h after LPS coinciding with the peak of neutrophil infiltration into the bladder wall. Selected cDNA microarray observations were confirmed by RNase protection assay. In conclusion, the cDNA array experimental approach provided a global profile of gene expression changes in bladder tissue after stimulation with LPS. SOM techniques identified functionally significant gene clusters, providing a powerful technical basis for future analysis of mechanisms of bladder inflammation.
Asunto(s)
Cistitis/genética , Animales , Cistitis/inducido químicamente , Cistitis/metabolismo , Regulación hacia Abajo , Perfilación de la Expresión Génica , Mediadores de Inflamación/metabolismo , Cinética , Lipopolisacáridos , Ratones , FN-kappa B/biosíntesis , FN-kappa B/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/biosíntesis , Ribonucleasas/química , Regulación hacia ArribaRESUMEN
Interstitial cystitis (IC) is a debilitating disease that has been adversely affecting the quality of women's lives for many years. The trigger in IC is not entirely known, and a role for the sensory nerves in its pathogenesis has been suggested. In addition to inflammation, increased mast cell numbers in the detrusor muscle have been reported in a subset of IC patients. Experimentally, several lines of evidence support a central role for substance P and neurokinin-1 (NK-1) receptors in cystitis. The availability of mice genetically deficient in neurokinin-1 receptor (NK-1R(-/-)) allows us to directly evaluate the importance of substance P in cystitis. An unexpected finding of this investigation is that NK-1R(-/-) mice present increased numbers of mast cells in the bladder when compared with wild-type control mice. Despite the increase in mast cell numbers, no concomitant inflammation was observed. In addition, bladder instillation of wild-type mice with a sensitizing antigen induces activation of mast cells and an acute inflammatory response characterized by plasma extravasation, edema, and migration of neutrophils. Antigen-sensitized NK-1R(-/-) mice also exhibit bladder mast cell degranulation in response to antigen challenge. However, NK-1R(-/-) mice are protected from inflammation, failing to present bladder inflammatory cell infiltrate or edema in response to antigen challenge. This work presents the first evidence of participation of NK-1 receptors in cystitis and a mandatory participation of these receptors on the chain of events linking mast cell degranulation and inflammation.
Asunto(s)
Cistitis Intersticial/etiología , Receptores de Neuroquinina-1/fisiología , Animales , Degranulación de la Célula/inmunología , Cistitis Intersticial/inmunología , Cistitis Intersticial/patología , Dinitrobencenos/administración & dosificación , Dinitrofenoles/administración & dosificación , Femenino , Hipersensibilidad Inmediata/etiología , Hipersensibilidad Inmediata/patología , Inmunización , Mastocitos/inmunología , Ratones , Ratones Noqueados , Ovalbúmina/administración & dosificación , Receptores de Neuroquinina-1/deficiencia , Sustancia P/fisiología , Vejiga Urinaria/patologíaRESUMEN
In 120 adult Vietnamese patients with uncomplicated falciparum malaria the efficacy of, and tolerance to, mefloquine (M) vs the combination of mefloquine + sulfadoxine + pyrimethamine (MSP) was studied in a double-blind, randomized comparative trial with chloroquine. Also, a double-blind dose finding study of MSP was performed in 120 Vietnamese children with uncomplicated falciparum malaria. In the adults the mean parasite clearance time with M was 3.8 d and with MSP 3.6 d. Defervescence occurred in 2.9 and 3.0 d respectively for M and MSP. There was a 36.8% resistance rate in 38 patients treated with chloroquine. 96% of the children were sensitive or showed a delayed RI response. The lowest dose of MSP (10 mg/kg M + 20 mg/kg S + 1.0 mg/kg P, 1 tablet Fansimef) was as effective as 1.5-2x this dose in children weighing 23-30 kg. Side effects were mild, except for vomiting which required alternative therapy in 4 patients.
Asunto(s)
Antimaláricos/uso terapéutico , Malaria/tratamiento farmacológico , Mefloquina/análogos & derivados , Mefloquina/uso terapéutico , Pirimetamina/uso terapéutico , Sulfadoxina/uso terapéutico , Sulfanilamidas/uso terapéutico , Adolescente , Adulto , Animales , Antimaláricos/administración & dosificación , Antimaláricos/efectos adversos , Niño , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Combinación de Medicamentos/administración & dosificación , Combinación de Medicamentos/efectos adversos , Combinación de Medicamentos/uso terapéutico , Femenino , Humanos , Malaria/sangre , Masculino , Mefloquina/administración & dosificación , Mefloquina/efectos adversos , Persona de Mediana Edad , Plasmodium falciparum/aislamiento & purificación , Estudios Prospectivos , Pirimetamina/administración & dosificación , Pirimetamina/efectos adversos , Distribución Aleatoria , Sulfadoxina/administración & dosificación , Sulfadoxina/efectos adversos , Factores de TiempoRESUMEN
Individual dental patterns have been explored by direct comparison of test bites from several sets of young adult monozygotic twins. For this purpose, epoxy models from the dentition of each twin were used for experimental tooth indentations and converted to radiographic contact profiles. These sharply outlined radiographic bitemark patterns were then subjected to a computerized comparison, involving electronic storage and correlations. Despite similar developmental morphology of individual teeth, there were significant variations between the twins in each pair with respect to the individual arrangements of the anterior teeth in the dental arch; the teeth had distinctly different rotations, sometimes reflecting a mirror image of the twin-pair bitemark patterns. Thus, the computer comparison made it clear that in terms of occlusal arch form and individual tooth positions, even so-called identical twins are in fact not dentally identical.