RESUMEN
The spin absorption process in a ferromagnetic material depends on the spin orientation relative to the magnetization. Using a ferromagnet to absorb the pure spin current created within a lateral spin valve, we evidence and quantify a sizable orientation dependence of the spin absorption in Co, CoFe, and NiFe. These experiments allow us to determine the spin-mixing conductance, an elusive but fundamental parameter of the spin-dependent transport. We show that the obtained values cannot be understood within a model considering only the Larmor, transverse decoherence, and spin diffusion lengths, and rather suggest that the spin-mixing conductance is actually limited by the Sharvin conductance.
RESUMEN
Spin injection and detection in Co60Fe40-based all-metallic lateral spin valves have been studied at both room and low temperatures. The obtained spin signals amplitudes have been compared to those of identical Ni80Fe20-based devices. The replacement of Ni80Fe20 by CoFe allows increasing the spin signal amplitude by up to one order of magnitude, thus reaching 50 mΩ at room temperature. The spin signal dependence with the distance between the ferromagnetic electrodes has been analyzed using both a 1D spin-transport model and finite element method simulations. The enhancement of the spin signal amplitude when using CoFe electrodes can be explained by a higher effective polarization.
RESUMEN
In this letter, we discuss the shift observed in spintronics from the current-perpendicular-to-plane geometry towards lateral geometries, illustrating the new opportunities offered by this configuration. Using CoFe-based all-metallic LSVs, we show that giant magnetoresistance variations of more than 10% can be obtained, competitive with the current-perpendicular-to-plane giant magnetoresistance. We then focus on the interest of being able to tailor freely the geometries. On the one hand, by tailoring the non-magnetic parts, we show that it is possible to enhance the spin signal of giant magnetoresistance structures. On the other hand, we show that tailoring the geometry of lateral structures allows creating a multilevel memory with high spin signals, by controlling the coercivity and shape anisotropy of the magnetic parts. Furthermore, we study a new device in which the magnetization direction of a nanodisk can be detected. We thus show that the ability to control the magnetic properties can be used to take advantage of all the spin degrees of freedom, which are usually occulted in current-perpendicular-to-plane devices. This flexibility of lateral structures relatively to current-perpendicular-to-plane structures is thus found to offer a new playground for the development of spintronic applications.
RESUMEN
A subtype of maturity-onset diabetes of the young (MODY) is caused by mutations of the glucokinase gene, an enzyme expressed in pancreatic beta-cells and the liver. To assess the consequences of a functional alteration of glucokinase at the level of the liver, endogenous (hepatic) glucose production and glucose cycling (an indirect assessment of hepatic glucokinase activity) were measured with 2-2H glucose and 6,6-2H glucose in patients who developed MODY because of the V203A mutation of glucokinase, and in control subjects at similar levels of glycemia. Measurements were performed in the postabsorptive state and after ingestion of 13C-labeled glucose. In the postabsorptive state, MODY patients had normal glucose production (10.9 +/- 1.3 vs. 11.3 +/- 0.6 micromol x kg(-1) x min(-1)) but decreased glucose cycling (0.6 +/- 0.3 vs. 1.5 +/- 0.3 micromol x kg(-1) x min(-1); P < 0.05) when compared with control subjects. However, at plasma glucose and insulin levels similar to those observed in MODY patients, control subjects' glucose production was markedly lower (3.2 +/- 1.5 micromol x kg(-1) x min(-1). After glucose ingestion, endogenous glucose production was reduced by only 29% in MODY patients compared with 80% in control subjects at a similar level of hyperglycemia (P < 0.05). This suggests that the V203A mutation of glucokinase results in decreased activity of glucokinase in liver cells. Thus endogenous glucose production is inadequately inhibited by hyperglycemia in MODY patients, possibly as a result of impaired hepatic glucokinase activity. These alterations contribute to the pathogenesis of hyperglycemia.
Asunto(s)
Diabetes Mellitus Tipo 2/genética , Glucoquinasa/genética , Adulto , Glucemia/metabolismo , Péptido C/sangre , Calorimetría , Diabetes Mellitus Tipo 2/enzimología , Femenino , Glucosa/metabolismo , Humanos , Insulina/sangre , Hígado/metabolismo , Masculino , Persona de Mediana Edad , Mutación , Oxidación-ReducciónRESUMEN
The aim of our study was to investigate the relative prevalence of the different forms of diabetes in young adults and their respective clinical characteristics. Included were 51 nonobese patients (BMI < 27 kg/m2) with diabetes diagnosed before age 40, excluding typical IDDM. Each patient was subjected to screening for glucokinase gene (MODY2) and mitochondrial DNA (at nucleotide 3243) mutations, to HLA class II genotyping, and screening for the presence of islet cell antibodies (ICAs) and anti-GAD antibodies. Informative families were analyzed for linkage of diabetes to chromosome 12q (MODY3). Based on clinical criteria, patients were subdivided into MODY (n = 19) and non-MODY (n = 32). In the MODY group, we identified three patients with MODY2, one with the 3243 mitochondrial mutation, and another with autoimmune diabetes. One of the five MODY families available for linkage study was shown to have MODY3. In the non-MODY group, we found five patients with autoimmune diabetes and one with MODY2. No clinical parameter was helpful to classify patients in one of these subclasses of diabetes; however, the glucagon-stimulated C-peptide was useful to discriminate between MODY2 patients and the others. In conclusion, young and lean non-insulin-dependent diabetic patients constitute a very heterogeneous group, although they present similar clinical characteristics. The clinical distinction of MODY and non-MODY patients allows correct classification in, at most, 75% of the patients and thus is not sufficient to predict clinical course. However, immunological and genetic parameters allowed us to classify only 25% of the patients in specific diagnostic classes.
Asunto(s)
Cromosomas Humanos Par 12/genética , Diabetes Mellitus/clasificación , Diabetes Mellitus/diagnóstico , Glucoquinasa/genética , Mutación/genética , Adulto , Autoanticuerpos/sangre , Estudios de Cohortes , Diabetes Mellitus/genética , Diabetes Mellitus/inmunología , Familia , Femenino , Ligamiento Genético , Marcadores Genéticos , Glutamato Descarboxilasa/inmunología , Haplotipos/genética , Humanos , Islotes Pancreáticos/inmunología , Escala de Lod , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , ARN de Transferencia de Leucina/genéticaRESUMEN
The characterization of the major antigenic determinants present in human protamine P1 has been carried out by the use of specific rabbit polyclonal and mouse monoclonal antisera raised against protamine P1. This basic protein, the full amino acid sequence of which has been determined here, has been cleaved by cyanogen bromide and/or by pepsin to generate a discrete number of peptides. These have been purified, characterized by partial amino acid sequencing and used for the determination of their antigenic reactivities with antisera to native protamine P1. Both rabbit polyclonal and mouse monoclonal antibodies were able to recognize the NH2-terminal CNBr peptide encompassing residues 1-36 to the same extent as the intact protamine. A minor epitope present on the COOH-terminal peptide 37-50 could be detected only with the polyclonal rabbit antisera. Attempts to further cleave the P1 molecule in order to isolate peptides shorter than fragments 1-36 whilst retaining full antigenic reactivities, were unsuccessful. This suggests that the epitopes in P1 are conformation-dependent and located for the most part on the amino-terminal half of the molecule, which comprises the characteristic central arginine cluster. The implication of these findings for the studies of the specificities of autoantibodies in sera from infertile and vasectomized individuals is discussed.
Asunto(s)
Epítopos/análisis , Protaminas/inmunología , Secuencia de Aminoácidos , Animales , Cromatografía Líquida de Alta Presión , Bromuro de Cianógeno , Ensayo de Inmunoadsorción Enzimática , Humanos , Masculino , Ratones , Datos de Secuencia Molecular , Péptidos/análisis , Feniltiohidantoína , Protaminas/análisis , ConejosRESUMEN
Changes in the cytosolic free Ca2+ concentration, [Ca2+]i, have been proposed to mediate the regulation of the secretion of pituitary hormones by hypothalamic peptides. Using an intracellularly trapped fluorescent Ca2+ probe, quin2, [Ca2+]i was monitored in GH3 cells. Somatostatin lowers [Ca2+]i in a dose dependent manner from a prestimulatory level of 120 +/- 4 nM (SEM, n = 13) to 78 +/- 9 nM (n = 5) at 10(-7)M; the effect is half maximal at 2 X 10(-9) M somatostatin. The decrease in [Ca2+]i occurs rapidly after somatostatin addition and a lowered steady state [Ca2+]i is maintained for several minutes. Somatostatin does not inhibit the rapid rise in [Ca2+]i elicited by thyrotropin releasing hormone (TRH) and can still cause a decrease in [Ca2+]i in the presence of TRH (10(-7)M). Concomitantly with its action on [Ca2+]i somatostatin causes hyperpolarization of GH3 cells assessed with the fluorescent probe bis-oxonol. The lowering of [Ca2+]i by somatostatin is however not only due to reduced Ca2+ influx through voltage dependent Ca2+ channels, since it persists in the presence of the channel blocker verapamil. These results suggest that somatostatin may exert its inhibitory action on pituitary hormone secretion by decreasing [Ca2+]i.
Asunto(s)
Calcio/metabolismo , Neoplasias Hipofisarias/fisiopatología , Somatostatina/farmacología , Aminoquinolinas , Animales , Línea Celular , Citosol/efectos de los fármacos , Citosol/metabolismo , Colorantes Fluorescentes , Cinética , Potenciales de la Membrana/efectos de los fármacos , Potasio/farmacología , Ratas , Espectrometría de Fluorescencia , Hormona Liberadora de Tirotropina/farmacologíaRESUMEN
Muscarinic cholinergic agonists have been shown to inhibit PRL secretion in normal and tumor-derived pituitary cells. Evidence from experiments with the fluorescent Ca2+ probe quin 2 shows that carbachol, acting through muscarinic acetylcholine receptors, lowers the cytosolic free Ca2+ concentration ([Ca2+]i), in GH3 cells. A decrease in [Ca2+]i is observed rapidly after carbachol addition, the lowered steady state [Ca2+]i is maintained, and upon the addition of atropine [Ca2+]i returns to the initial basal value. The lowering from a basal [Ca2+]i, averaging 110 +/- 2 nM (+/- SEM, n = 9), to a steady state [Ca2+]i of 63 +/- 4 nM (+/- SEM, n = 5) at 10 micron carbachol is dose dependent, a significant decrease from basal [Ca2+]i being observed at 0.1 micron. Carbachol does not prevent TRH-induced mobilization of Ca2+ but attenuates the resulting rise in [Ca2+]i. The lowering of steady state [Ca2+]i and the attenuation of the rise in [Ca2+]i provoked by stimulators of PRL secretion could explain the inhibition of both basal and stimulated PRL secretion. Concomitantly with the action on [Ca2+]i, carbachol causes hyperpolarization of GH3 cells. Together with the established inhibition of adenylate cyclase by muscarinic cholinergic agonists, these findings suggest a relation between changes in trans-membrane Ca2+ fluxes and cAMP generation.
Asunto(s)
Calcio/metabolismo , Carbacol/farmacología , Células Clonales/metabolismo , Hipófisis/efectos de los fármacos , Neoplasias Hipofisarias/metabolismo , Animales , Atropina/farmacología , Línea Celular , Citosol/metabolismo , Relación Dosis-Respuesta a Droga , Potenciales de la Membrana , Hipófisis/metabolismo , Potasio/farmacología , Ratas , Receptores Colinérgicos/metabolismo , Hormona Liberadora de Tirotropina/farmacologíaRESUMEN
The cytosolic free calcium concentration, [Ca2+]i, was monitored in single rat lactotrophs in primary culture with the fluorescent probe Fura 2. It was found that lactotrophs are very heterogeneous in their [Ca2+]i response to TRH and dopamine, the major physiological regulators of PRL secretion. While in most lactotrophs TRH raises [Ca2+]i, the kinetics of this rise and the magnitude of its first and second phases vary considerably. For dopamine two clearly divergent response types can be observed. In part of the lactotrophs dopamine causes a lowering of [Ca2+]i from elevated levels, whereas in about 40% of the lactotrophs dopamine leads to a transient rise of [Ca2+]i. The present study reveals subclasses of lactotrophs with distinct [Ca2+]i response characteristics. It is suggested that such response type heterogeneity is a means of optimizing the secretory response to the complex regulatory influences on the pituitary.
Asunto(s)
Calcio/metabolismo , Dopamina/farmacología , Adenohipófisis/metabolismo , Prolactina/metabolismo , Hormona Liberadora de Tirotropina/farmacología , Animales , Células Cultivadas , Citosol/efectos de los fármacos , Citosol/metabolismo , Cinética , Masculino , Adenohipófisis/efectos de los fármacos , Ratas , Ratas EndogámicasRESUMEN
Thyrotropin releasing hormone (TRH) accelerates the turnover of phosphatidylinositol in GH3 cells ('phospholipid response'). From the analysis of inositol phosphates in the presence of Li+ which inhibits their dephosphorylation, it can be concluded that the hydrolysis of phosphatidylinositol 4,5-biphosphate, and possibly of phosphatidylinositol 4-phosphate by phospholipase C is markedly accelerated by TRH. It appears that this reaction initiates the acceleration of phosphatidylinositol turnover. The specificity of hormonally regulated phospholipase C reaction for polyphosphoinositides has important implications for the potential role of the phospholipid response as a mechanism of membrane signal transduction.
Asunto(s)
Fosfatidilinositoles/metabolismo , Fosfolipasas/metabolismo , Neoplasias Hipofisarias/enzimología , Hormona Liberadora de Tirotropina/farmacología , Fosfolipasas de Tipo C/metabolismo , Animales , Línea Celular , Cloruros/farmacología , Hidrólisis , Cinética , Litio/farmacología , Cloruro de Litio , RatasRESUMEN
Pertussis toxin, PT, abolishes inhibitory regulation of adenylate cyclase by cell surface receptors. Inhibitors of adenylate cyclase in GH3 cells, namely somatostatin and the muscarinic cholinergic agonist carbachol, lower the cytosolic free Ca2+ concentration. [Ca2+]i and cause hyperpolarization. These responses are selectively abolished by PT. It is concluded that the effects of somatostatin and carbachol to lower [Ca2+]i and to hyperpolarize are secondary to their inhibitory action on adenylate cyclase. In contrast, PT does not impair the TRH induced rise in [Ca2+]i in GH3 cells demonstrating that the coupling of TRH receptors to Ca2+ mobilization is not mediated by a PT substrate.
Asunto(s)
Toxinas Bacterianas/farmacología , Calcio/metabolismo , Citosol/metabolismo , Neoplasias Hipofisarias/metabolismo , Somatostatina/farmacología , Toxina de Adenilato Ciclasa , Adenilil Ciclasas/metabolismo , Animales , Carbacol/farmacología , Línea Celular , Toxina del Pertussis , Ratas , Hormona Liberadora de Tirotropina/farmacología , Péptido Intestinal Vasoactivo/farmacología , Factores de Virulencia de BordetellaRESUMEN
alpha-MSH and other fragments of ACTH are potent stimulators of GH release in vivo. The action of such peptides and of extracts of the neurointermediary lobe (NIL) of rat pituitary, a source of endogenous MSH-related peptides, on GH release was investigated in vitro. Peptides with the core sequence of alpha-MSH stimulate GH secretion by primary cultures of rat anterior pituitary cells; however, both the absolute and the relative potencies of these peptides exclude the involvement of melanotropic receptors comparable in specificity to the extrapituitary receptors for these hormones. Extracts of the NIL of rat pituitary stimulate GH release in vitro and the bulk of the releasing activity can be attributed to one (or several) factors with an apparent mass of approx. 10 000 M.W. that can be partially purified by HPLC. The active principle appears to be distinct from both beta-LPH and the human pancreatic GHRF. Thus, while rat NIL contains GH-releasing activity that can be demonstrated in vitro, a direct link to the potent action of MSH-related peptides on GH release in vivo cannot be established, and the action of these peptides in vivo must therefore rely on mechanisms which are not expressed in the in vitro system.
Asunto(s)
Hormona del Crecimiento/metabolismo , Hipófisis/análisis , Animales , Hormona Liberadora de Hormona del Crecimiento/fisiología , Técnicas In Vitro , Masculino , Hormonas Estimuladoras de los Melanocitos/fisiología , Hipófisis/metabolismo , Ratas , Ratas Endogámicas , Extractos de Tejidos/farmacología , beta-Lipotropina/fisiologíaRESUMEN
Fairly small amounts of air (usually one loop visible) were found in the small intestine of 41,2 plus or minus 3,4 p. cent (at the 95 p. cent confidence level) of a series of 827 adults (553 inpatients and 274 outpatients). Air in the small intestine was noted more frequently in the hospitalized patients (45,2 plus or minus 4,1 p. cent) than in the outpatients (33,2 plus or minus 5,6 p. cent) (p. less than 0,001). This study confirms the hypothesis, contrary to conventional data, that the presence of air in the small intestine occurs sufficiently frequently for it not to be considered pathological. Air is more frequently visible in the proximal jejunum (48,4 p. cent) than in the ileum (27,3 p. cent), and is noted in the umbilical region, the transition zone, in 24,3 p. cent of cases. The mean diameter of th proximal jejunal loops is 25,6 mm (standard deviation 3,7 mm). The thickness of the proximal jejunal folds varies between 1 and 2 mm, the interfold thickness being 3 to 6 mm. The thickness of the small intestine wall (measured in the interfold space) is less than 1,5 mm. These figures relate to direct measurement of radiographic images, without correction due to enlargement.