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Precision measurements by the Alpha Magnetic Spectrometer (AMS) on the International Space Station of the deuteron (D) flux are presented. The measurements are based on 21×10^{6} D nuclei in the rigidity range from 1.9 to 21 GV collected from May 2011 to April 2021. We observe that over the entire rigidity range the D flux exhibits nearly identical time variations with the p, ^{3}He, and ^{4}He fluxes. Above 4.5 GV, the D/^{4}He flux ratio is time independent and its rigidity dependence is well described by a single power law âR^{Δ} with Δ_{D/^{4}He}=-0.108±0.005. This is in contrast with the ^{3}He/^{4}He flux ratio for which we find Δ_{^{3}He/^{4}He}=-0.289±0.003. Above â¼13 GV we find a nearly identical rigidity dependence of the D and p fluxes with a D/p flux ratio of 0.027±0.001. These unexpected observations indicate that cosmic deuterons have a sizable primarylike component. With a method independent of cosmic ray propagation, we obtain the primary component of the D flux equal to 9.4±0.5% of the ^{4}He flux and the secondary component of the D flux equal to 58±5% of the ^{3}He flux.
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We present the precision measurements of 11 years of daily cosmic positron fluxes in the rigidity range from 1.00 to 41.9 GV based on 3.4×10^{6} positrons collected with the Alpha Magnetic Spectrometer (AMS) aboard the International Space Station. The positron fluxes show distinctly different time variations from the electron fluxes at short and long timescales. A hysteresis between the electron fluxes and the positron fluxes is observed with a significance greater than 5σ at rigidities below 8.5 GV. On the contrary, the positron fluxes and the proton fluxes show similar time variation. Remarkably, we found that positron fluxes are modulated more than proton fluxes with a significance greater than 5σ for rigidities below 7 GV. These continuous daily positron fluxes, together with AMS daily electron, proton, and helium fluxes over an 11-year solar cycle, provide unique input to the understanding of both the charge-sign and mass dependencies of cosmic rays in the heliosphere.
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We report the properties of primary cosmic-ray sulfur (S) in the rigidity range 2.15 GV to 3.0 TV based on 0.38×10^{6} sulfur nuclei collected by the Alpha Magnetic Spectrometer experiment (AMS). We observed that above 90 GV the rigidity dependence of the S flux is identical to the rigidity dependence of Ne-Mg-Si fluxes, which is different from the rigidity dependence of the He-C-O-Fe fluxes. We found that, similar to N, Na, and Al cosmic rays, over the entire rigidity range, the traditional primary cosmic rays S, Ne, Mg, and C all have sizeable secondary components, and the S, Ne, and Mg fluxes are well described by the weighted sum of the primary silicon flux and the secondary fluorine flux, and the C flux is well described by the weighted sum of the primary oxygen flux and the secondary boron flux. The primary and secondary contributions of the traditional primary cosmic-ray fluxes of C, Ne, Mg, and S (even Z elements) are distinctly different from the primary and secondary contributions of the N, Na, and Al (odd Z elements) fluxes. The abundance ratio at the source for S/Si is 0.167±0.006, for Ne/Si is 0.833±0.025, for Mg/Si is 0.994±0.029, and for C/O is 0.836±0.025. These values are determined independent of cosmic-ray propagation.
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Carbono , Magnesio , Neón , Azufre , Fenómenos MagnéticosRESUMEN
We present the precision measurements of 11 years of daily cosmic electron fluxes in the rigidity interval from 1.00 to 41.9 GV based on 2.0×10^{8} electrons collected with the Alpha Magnetic Spectrometer (AMS) aboard the International Space Station. The electron fluxes exhibit variations on multiple timescales. Recurrent electron flux variations with periods of 27 days, 13.5 days, and 9 days are observed. We find that the electron fluxes show distinctly different time variations from the proton fluxes. Remarkably, a hysteresis between the electron flux and the proton flux is observed with a significance of greater than 6σ at rigidities below 8.5 GV. Furthermore, significant structures in the electron-proton hysteresis are observed corresponding to sharp structures in both fluxes. This continuous daily electron data provide unique input to the understanding of the charge sign dependence of cosmic rays over an 11-year solar cycle.
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Infectious diseases in older people are much more frequent, and mortality from them is higher than in young people. Vaccination is the most effective and least expensive preventative measure for a number of infectious diseases. However, vaccines that are effective in young people are often ineffective in older people over 65, which is a result of a gradual decrease in the functional capacity of the immune systems, which occurs with age, and is called «immunosenescence¼. Age-related changes in the cellular and humoral immunity worsen the primary response to vaccines and weaken the development of long-term immunological memory. Recent studies suggest that one of the possible causes of the occurrence and maintenance of «immunosenescence¼ may be myeloid-derived suppressor cells (MDSCs). These cells have been shown to inhibit the functions of innate and adaptive immunity cells through a number of mechanisms. In this review, we provide information that emphasizes the role of MDSCs in inhibiting the immune response to vaccines during aging, and also substantiates possible ways to overcome this immunological obstacle.
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Inmunosenescencia , Células Supresoras de Origen Mieloide , Inmunidad Adaptativa , Adolescente , Anciano , Anciano de 80 o más Años , Envejecimiento , Humanos , VacunaciónRESUMEN
The search for new strategies for the prevention and control of osteoporosis is an urgent task. Functional foodstuffs and their components are of particular interest in this regard. The aim was to study the effect of bread enriched with protein, dietary fiber, calcium, iron and iodine on the state of the bone tissue of rats in a model of postmenopausal osteoporosis. Material and methods. The experiment was performed on sexually mature female Wistar rats divided into groups: K - control (sham-operated rats, not ovariectomized); Ð30 - osteoporosis model (animals were sacrificed 30 days after ovariectomy); groups Ð120 and Ð120+ - a model of osteoporosis (rats were sacrificed 120 days after ovariectomy). All animals were fed a standard vivary diet. For rats of the Ð120+ group, from the 40th to the 120th day, enriched bread was included in the diet in an amount of 6 g per 100 g of body weight per day. The bread was fortified with protein (whey protein, blood plasma proteins from farm animals), dietary fiber, calcium (eggshell), iron (purified hemoglobin) and iodized whey protein. Animals of groups K and Ð120 received unfortified bread in the same amount. Blood levels of total calcium (by colorimetric method), gonadotropins, testosterone, and estradiol (by enzyme-linked immunosorbent assay) were analyzed. Microtomographic evaluation of the architecture and mineral density of the trabecular part of the femur and lumbar vertebrae was performed. Histomorphological analysis of the uterus and femur of animals was performed. Results and discussion. In animals of the Ð120+ group, in comparison with the Ð120 sample, there was a decrease in blood testosterone and a marked compensatory release of follicle-stimulating hormone, while no changes were detected in the concentration of estradiol and the state of the uterus atrophied against the background of ovariectomy. There was an increase in the trabecular mineral density of the femur and lumbar vertebrae. The proportion of bone trabeculae in the total volume of the femoral metaphysis (BV/TV) in animals of the Ð120+ sample was 12.5±0.66% compared to 10.4±0.52% in the Ð120 group. The values of the structural model index (SMI) reflecting the loss of bone strength and the trabecularity coefficient (TbPf) in Ð120+ rats (1.44±0.07 and 5.96±0.29 1/mm) were significantly lower than these parameters in the Ð120 group (1.74±0.08; 9.13±0.46 1/mm, Ñ<0.05). The micro-architectural structure of the femur in the Ð120+ group of rats was close to that of the Ð30 sample, which serves as a model of the early stage of osteoporosis (SMI 1.42±0.07; TbPf 5.55±0.28 1/mm). The percentage of bone resorption perimeter and the number of osteoclasts in the Ð120+ femoral trabeculae were lower than in the Ð120 group. In the Ð120+ group, active osteoblasts were observed in a significant part of the resorption cavities. Cell differentiation more was observed in the osteogenic direction than in the adipogenic direction. Conclusion. Bread enriched with protein, fiber, calcium, iron and iodine, effectively weakens osteoporosis induced by ovariectomy in rats. Its inclusion in the diet may be beneficial for the prevention and treatment of systemic postmenopausal osteoporosis.
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Pan , Calcio de la Dieta/farmacología , Alimentos Fortificados , Yodo/farmacología , Hierro/farmacología , Osteoporosis Posmenopáusica , Animales , Modelos Animales de Enfermedad , Femenino , Fémur/metabolismo , Fémur/patología , Humanos , Yodo/química , Hierro/química , Vértebras Lumbares/metabolismo , Vértebras Lumbares/patología , Osteoporosis Posmenopáusica/dietoterapia , Osteoporosis Posmenopáusica/metabolismo , Osteoporosis Posmenopáusica/patología , Ovariectomía , Ratas , Ratas WistarRESUMEN
We studied the role of cytokines TGF-ß and TNFα in reduction of the cytolytic activity of NK cells towards tumor cells. Exogenous TGF-ß and TNFα reduced the sensitivity of MiaPaCa2 pancreatic adenocarcinoma cells to NK cytotoxicity, which was associated with reduction of ULBP-1 expression and increase of HLA-E, HLA-G, CD155, and CD112 expression on Mia-PaCa2 cells. Changes in the expression of ligands for NK receptors on tumor cells induced by TGF-ß and TNFα may contribute to reduction of cytotoxicity of tumor-associated NK cells and thus prevent an adequate antitumor immune response leading to the disease progress.
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Adenocarcinoma/inmunología , Citotoxicidad Inmunológica/efectos de los fármacos , Células Asesinas Naturales/efectos de los fármacos , Neoplasias Pancreáticas/inmunología , Factor de Crecimiento Transformador beta/farmacología , Factor de Necrosis Tumoral alfa/farmacología , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Línea Celular Tumoral , Interacciones Farmacológicas , Antígenos de Histocompatibilidad Clase I/metabolismo , Humanos , Células Asesinas Naturales/inmunología , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologíaRESUMEN
The number of CD3(+)CD56-HLA-G(+) cells in the peripheral blood of breast cancer patients was shown to increase by 2 times. Our results and published data suggest that the increase in the relative content of CD3(+)CD56-HLA-G(+) cells in the circulating blood in breast cancer contributes to tumor development due to suppression of antitumor immunity.
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Neoplasias de la Mama/inmunología , Antígenos HLA-G/inmunología , Inmunidad Innata , Subgrupos de Linfocitos T/inmunología , Adulto , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Complejo CD3/genética , Complejo CD3/inmunología , Antígeno CD56/genética , Antígeno CD56/inmunología , Estudios de Casos y Controles , Femenino , Citometría de Flujo , Expresión Génica , Antígenos HLA-G/genética , Humanos , Inmunofenotipificación , Interferón gamma/genética , Interferón gamma/inmunología , Interleucina-10/genética , Interleucina-10/inmunología , Recuento de Linfocitos , Persona de Mediana Edad , Estadificación de Neoplasias , Subgrupos de Linfocitos T/patología , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/inmunologíaRESUMEN
Lignin monophenols have been measured in the cupric oxide oxidation products from lichens of different systematic groups. It is shown for the first time that syringyl structures in most lichens strongly dominate over vanillyl and p-hydroxyl ones (S/V 7-583, S/P 3-30). This distinguishes lichens from algae and mosses (p-hydroxyl phenols are dominant) and from higher plants (S/V ratios are from 0 in gymnosperms to 1.1-5.2 in angiosperms). Molecular ratios of phenols as well as the ratios of acids to aldehydes in lichens were different from lignin of higher plants, suggesting contribution of non-lignin phenols in CuO oxidation products. The contents of syringyl and vanillyl phenols in some lichen species were comparable to non-woody tissues of higher plants. Results of the study suggest that lichens can be important source of aromatic structures in soils and hydrosphere, particularly in the regions were lichens are abundant.
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Líquenes/química , Lignina/análogos & derivados , Fenoles/análisis , Lignina/análisisRESUMEN
We studied the effects of fucoidan (L-selectin ligand) on the expression and SDF-1-induced internalization of CXCR4 receptor on human NK cells of healthy donors and tumor patients. Fucoidan stimulated the expression of surface CXCR4 due to mobilization of the intracellular pool. The effect of fucoidan on CXCR4 expression in cancer patients was low. It was hypothesized that L-selectin-dependent migration of circulating NK cells along the SDF-1 chemokine gradient is reduced in cancer patients.
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Células Asesinas Naturales/citología , Células Asesinas Naturales/metabolismo , Selectina L/metabolismo , Receptores CXCR4/metabolismo , Adulto , Anciano , Movimiento Celular/efectos de los fármacos , Células Cultivadas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polisacáridos/farmacologíaRESUMEN
Isolated mitotic chromosomes are able to form complexes with phosphatidylcholine liposomes in the presence and absence of Ca2+ ions, in the latter case in the presence of polyamines. Interactions with chromosomes stimulates liposome fusion. The fusion is promoted by condensed and EDTA-decondensed chromosomes.
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Cromosomas/metabolismo , Liposomas/metabolismo , Fusión de Membrana , Metafase , 1,2-Dipalmitoilfosfatidilcolina/metabolismo , Adsorción , Animales , Calcio/farmacología , Cromatina/metabolismo , ADN/metabolismo , Ácido Edético/farmacología , Transferencia de Energía , Ratones , Microscopía Electrónica , Fosfolípidos/metabolismo , Espermidina/farmacologíaRESUMEN
In the course of experimental CCl4-induced cirrhosis, an increase of the membrane-associated factor stimulating 3T3 cells' proliferation in vitro was observed. Gel filtration showed an approximate molecular mass of 150 kDa. Extraction of growth stimulatory activity by liver perfusion in situ demonstrated a peripheral plasma membrane protein localization. The activity increased with an increasing number of CCl4 treatments, reaching a maximum at the tenth intoxication, faster than the proliferation of connective tissues. Cessation of treatment caused a decrease in activity to the level of untreated liver, although the amount of fibroblast-like cells remained large, which is evidence in favour of an hepatocyte origin of the factor.
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Intoxicación por Tetracloruro de Carbono/metabolismo , Cirrosis Hepática Experimental/inducido químicamente , Hígado/metabolismo , Animales , Cromatografía en Gel , ADN/metabolismo , Hígado/efectos de los fármacos , Masculino , Ratones , Mitógenos/metabolismo , Timidina/metabolismoRESUMEN
We show that N-1 in adenine of chromosomal DNA is methylated by treatment of metaphase chromosomes with dimethylsulphate while this is not the case in chromatin. The data on methylation are consistent with those obtained from the experiments with S1-nuclease treatment of chromatin and chromosomes. This suggests a disarrangement of DNA secondary structure in the metaphase chromosomes.
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Cromosomas/análisis , ADN/análisis , Metafase , Animales , Secuencia de Bases , Línea Celular , Fibroblastos/análisis , Metilación , RatonesRESUMEN
The outer surface of isolated metaphase chromosomes has been investigated by a method of thermally activated tritium labelling. We show that both chromosomal proteins and DNA are tritium-labelled. Fractionation of the chromosomal proteins reveals that scaffold proteins are the most labelled in condensed and EDTA-decondensed chromosomes. Exposition of some scaffold proteins on the outer surface of metaphase chromosomes is suggested.
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Proteínas Cromosómicas no Histona/metabolismo , Cromosomas , Metafase , Animales , Fibroblastos/metabolismo , Ratones , Microscopía Electrónica , TritioRESUMEN
Alkaliphilic bacterial strains producing the enzyme cyclodextrin glucanotransferase were cultivated on solid agar medium containing an indicator system detecting the enzyme. The growth of the colony and the surrounding diffusion zone, due to the enzyme, were measured by the image analysis during the cultivation. It was possible to differentiate between relatively similar clones by observing quantitatively the changes at and around the colony. Optimal experimental conditions for such measurements are discussed. The image analysis technique provides a potential tool for characterizing microbes grown on solid media.
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Bacterias/crecimiento & desarrollo , Técnicas Bacteriológicas , Procesamiento de Imagen Asistido por Computador/métodos , Medios de Cultivo , Glucosiltransferasas/análisisRESUMEN
The amyloid cascade hypothesis of Alzheimer's disease (AD) postulates that accumulation in the brain of amyloid ß-peptide (Aß) is the primary trigger for neuronal loss specific to this pathology. In healthy brain, Aß levels are regulated by a dynamic equilibrium between Aß release from the amyloid precursor protein (APP) and its removal by perivascular drainage or by amyloid-degrading enzymes (ADEs). During the last decade, the ADE family was fast growing, and currently it embraces more than 20 members. There are solid data supporting involvement of each of them in Aß clearance but a zinc metallopeptidase neprilysin (NEP) is considered as a major ADE. NEP plays an important role in brain function due to its role in terminating neuropeptide signalling and its decrease during ageing or after such pathologies as hypoxia or ischemia contribute significantly to the development of AD pathology. The recently discovered mechanism of epigenetic regulation of NEP by the APP intracellular domain (AICD) opens new avenues for its therapeutic manipulation and raises hope for developing preventive strategies in AD. However, consideration needs to be given to the diverse physiological roles of NEP. This paper critically evaluates general biochemical and physiological functions of NEP and their therapeutic relevance.
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Repressor element-1 silencing transcription factor (REST) is a candidate modulator of gene expression during status epilepticus in the rodent. In such models, full-length REST and the truncated REST4 variant are induced and can potentially direct differential gene expression patterns. We have addressed the regulation of these REST variants in rodent hippocampal seizure models and correlated this with expression of the proconvulsant, substance P encoding, PPT-A gene. REST and REST4 were differentially regulated following kainic acid stimulus both in in vitro and in vivo models. REST4 was more tightly regulated than REST in both models and its transient expression correlated with that of the differential regulation of PPT-A. Consistent with this, overexpression of a truncated REST protein (HZ4, lacking the C-terminal repression domain) increased expression of the endogenous PPT-A gene. Similarly the proximal PPT-A promoter reporter gene construct was differentially regulated by the distinct REST isoforms in hippocampal cells with HZ4 being the major inducer of increased reporter expression. Furthermore, REST and REST4 proteins were differentially expressed and compartmentalized within rat hippocampal cells in vitro following noxious stimuli. This differential localization of the REST isoforms was confirmed in the CA1 region following perforant path and kainic acid induction of status epilepticus in vivo. We propose that the interplay between REST and REST4 alter the expression of proconvulsant genes, as exemplified by the PPT-A gene, and may therefore regulate the progression of epileptogenesis.
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Epilepsia/genética , Regulación de la Expresión Génica/fisiología , Proteínas Represoras/genética , Factores de Transcripción/genética , Animales , Células Cultivadas , Electroforesis en Gel de Poliacrilamida , Agonistas de Aminoácidos Excitadores , Técnica del Anticuerpo Fluorescente , Genes Reporteros/genética , Hipocampo/citología , Hipocampo/fisiología , Ácido Kaínico , Masculino , Microscopía Confocal , Neuropéptidos/biosíntesis , Neuropéptidos/genética , Técnicas de Cultivo de Órganos , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Convulsiones/genética , Estado Epiléptico/inducido químicamente , Estado Epiléptico/genéticaRESUMEN
Using polyclonal antibodies directed against acetylated isoforms of histone H4 (H4 acetylated at lysine positions 5, 8, 12, 16 and H4 tetraacetylated), indirect immunofluorescence revealed hyperacetylation for all H4 variants at the nucleolus organizer region (NOR) of metaphase chromosomes of the field bean Vicia faba. The transcriptionally inactive and late-replicating heterochromatin regions proved to be hypoacetylated at lysine positions 5, 8 and 12. The remaining chromatin showed average fluorescence. These patterns were altered when deacetylase was blocked by exposure of root tip meristems to trichostatin A for more than 2 h prior to fixation. Under these conditions, all lysine positions, except lysine 8, appeared to be hyperacetylated at the NOR and in addition at the prominent heterochromatin domains. This observation represents a hitherto unique switch of histone acetylation pattern during the cell cycle. This is apparently caused by deposition of acetylated H4. Ac5, 12 and 16 or by acetylation directly after replication, which later on becomes reduced (H4.Ac16) or even reversed (H4.Ac5 and 12) by deacetylase before cells enter mitosis.
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Fabaceae/metabolismo , Histonas/metabolismo , Plantas Medicinales , Acetilación , Animales , Especificidad de Anticuerpos , Ciclo Celular , Fabaceae/citología , Técnica del Anticuerpo Fluorescente Indirecta , Histonas/química , Histonas/inmunología , Región Organizadora del Nucléolo/metabolismo , ConejosRESUMEN
The acetylation pattern of H3 was studied on field bean chromosomes by means of indirect immunofluorescence using polyclonal antibodies recognizing H3 isoforms acetylated at lysine positions 9/18, 14 and 23. H3 was found to be hypoacetylated at lysine residues 9/18 and 14 within the heterochromatic regions composed of tandem repetitive Fok-I elements. Hyperacetylation of these residues was observed at the nucleolar organizing region (NOR) and in heterochromatic regions composed of repeats other than Fok-I elements. In contrast, H4 was underacetylated (H4.Ac5, 8, 12) or uniformly acetylated (H4.Ac16) at all heterochromatic regions, and acetylated above the average at all four lysines only within the NOR. Acetylation of lysine-23 of H3 was uniform, except for the NOR that showed no fluorescence. Inhibition of deacetylase during and after replication of heterochromatin by trichostatin A had no influence on the acetylation status of H3 but mediated an increase in acetylation of lysines 5, 12 and 16 of H4 above the average in the field bean heterochromatin. Thus, the chromosomal acetylation patterns of H4 and H3 of this species revealed common and divergent features. Whereas the acetylation level of H4 correlates well with the potential transcriptional activity and inversely with the time of replication of defined chromatin domains of Vicia faba, this is not generally true for H3.