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Understanding the mechanisms that connect heat and electron transport with crystal structures and defect chemistry is fundamental to develop materials with thermoelectric properties. In this work, we synthesized a series of self-doped compounds Cu2+x Mn1-x GeS4 through Cu for Mn substitution. Using a combination of powder X-ray diffraction, high resolution transmission electron microscopy and precession-assisted electron diffraction tomography, we evidence that the materials are composed of interconnected enargite- and stannite-type structures, via the formation of nanodomains with a high density of coherent interfaces. By combining experiments with ab initio electron and phonon calculations, we discuss the structure-thermoelectric properties relationships and clarify the interesting crystal chemistry in this system. We demonstrate that excess Cu+ substituted for Mn2+ dopes holes into the top of the valence band, leading to a remarkable enhancement of the power factor and figure of merit ZT.
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We have studied the formation process of the metal atomic filament for metal sulfide atomic switches by electrical measurement. The switching between ON and OFF states of the atomic switch is controlled by the application of the bias voltage for the atomic switches. The SET (OFF â ON) and RESET (ON â OFF) voltages were investigated for the atomic switch where the Ag2S or Cu2S layer were sandwiched between the Pt and Ag or Cu electrodes. The SET and RESET voltages of the Ag/Cu2S/Pt and Cu/Ag2S/Pt were close to those of the Ag/Ag2S/Pt atomic switch, and different from those of the Cu/Cu2S/Pt atomic switch. These results indicated that the dominant chemical species of the making and breaking part of the metal filament was Ag, and that the source of the metal filament was both the sulfide layer and the metal electrode.
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We have studied the stretch dependence of the electronic structure and vibrational energy for the 4,4'-bipyridine (BPY) single molecule junction, which was fabricated by the mechanically controllable break junction (MCBJ) using the highly stable nano MCBJ electrodes. The electronic structure and vibrational energy of the single molecule junction were studied by the current-voltage (I-V) curve and surface enhanced Raman scattering (SERS), respectively. The simultaneous SERS and I-V curve measurements revealed the lowest unoccupied molecular orbital (LUMO) and vibrational energy of the C-C stretching mode decreased with an increase in the metal-molecule distance. The molecular orbital energy shift and vibrational energy shift can be explained by the change in the degree of the hybridization of molecular and metal orbitals.
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Osteoclasts are multinucleated giant cells differentiated from monocyte-macrophage-lineage cells under stimulation of receptor activator of nuclear factor κ-B (RANK) ligand (RANKL) produced by osteoblasts and osteocytes. Although it has been reported that nitric oxide (NO) and reactive oxygen species (ROS) are involved in this process, the mechanism by which these labile molecules promote osteoclast differentiation are not fully understood. In this study, we investigated the formation and function of 8-nitro-cGMP, a downstream molecule of NO and ROS, in the process of osteoclast differentiation in vitro. 8-Nitro-cGMP was detected in mouse bone marrow macrophages and osteoclasts differentiated from macrophages in the presence of RANKL. Inhibition of NO synthase suppressed the formation of 8-nitro-cGMP as well as RANKL-induced osteoclast differentiation from macrophages. On the other hand, RANKL-induced osteoclast differentiation was promoted by addition of 8-nitro-cGMP to the cultures. In addition, 8-nitro-cGMP enhanced the mRNA expression of RANK, the receptor for RANKL. However, 8-bromo-cGMP, a membrane-permeable derivative of cGMP, did not have an effect on either RANKL-induced osteoclast differentiation or expression of the RANK gene. These results suggest that 8-nitro-cGMP is a novel positive regulator of osteoclast differentiation, which might help to explain the roles of NO and ROS in osteoclast differentiation.
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Diferenciación Celular , GMP Cíclico/análogos & derivados , Osteoclastos/fisiología , Ligando RANK/metabolismo , Animales , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Células Cultivadas , GMP Cíclico/metabolismo , GMP Cíclico/farmacología , Proteínas Quinasas Dependientes de GMP Cíclico/metabolismo , Inhibidores Enzimáticos/farmacología , Regulación de la Expresión Génica , Macrófagos/citología , Masculino , Ratones Endogámicos , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/metabolismo , Osteoclastos/citología , Osteoclastos/efectos de los fármacos , Ligando RANK/farmacología , Receptor Activador del Factor Nuclear kappa-B/genéticaRESUMEN
We have investigated the electric conductance and atomic structure of single molecular junctions of pyrazine (Py), 4,4'-bipyridine (BiPy), fullerene (C60), and 1,4-diaminobutane (DAB). The single molecular junctions were fabricated by breaking Au contacts between an Au tip and the Au electrode surface in the presence of the target molecules (breaking process) or approaching the Au tip to the Au electrode surface covered by the molecules (making process). In the making process, no major conductance state was observed in the conductance histogram for DAB, while single conductance states were observed for the π-conjugated molecules of Py (10 mG0, G0â¼ 77.45 µΩ-1), BiPy (3 mG0), and C60 (5 mG0). In contrast to the making process, two major conductance states were observed for Py (1 mG0 and 0.3 mG0), BiPy (0.6 mG0 and 0.2 mG0), and C60 (30 mG0 and 3 mG0) in the breaking process. The observed conductance behavior could be explained by the characters of the anchoring unit of molecules. In the making process, anchoring of molecules cannot be established by the point contact between the Au electrode and the localized lone pair of the N atom of DAB, Py, and BiPY, while molecules anchor on the Au electrode by using the plane-like contact between the Au electrode and the delocalized π electrons in the aromatic ring of Py, BiPY, and C60, which explains the difference in the observed conductance behavior between DAB and the π conjugated molecules of Py, BiPY, and C60 in the making process. In the breaking process, the delocalized π-electrons of Py, BiPY, and C60 can make a contact with the Au electrode surface and the lone pair on the N atom of DAB as well as Py and BiPY can bind to Au atoms, and therefore, single molecular junctions were formed for all systems. The present results indicate that the π-plane is important for making metal-molecule contacts and for the formation of the single molecular junction in the making process.
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This study investigated the occurrence of Escherichia coli pathotypes in sanitary wastewater and drinking water in a Bangladeshi urban slum and the potential associations between these sources. We examined 621 E. coli isolates from sanitary wastewater and stored drinking water by multiplex PCR and dual-index sequencing, classifying them into eight pathotypes based on 14 virulence genes and additionally evaluating the possession of the human-specific E. coli genetic biomarker H8. The proportions of pathogenic E. coli were significantly different (P < 0·001) between wastewater (18·6%) and drinking water (1·7%). StIb-positive enterotoxigenic E. coli (ETEC) were predominant in wastewater, indicating that people in the site carried ETEC. In contrast, no ETEC was present in drinking water and the proportion of H8-positive isolates was significantly smaller (7·8%) than that in wastewater (16·3%) (P = 0·001). Our findings indicate that sanitary wastewater from the slum was heavily contaminated with pathogenic E. coli, posing a great health risk. Furthermore, E. coli contamination of drinking water could be derived from not only human but also other sources. SIGNIFICANCE AND IMPACT OF THE STUDY: Sanitary wastewater from an urban slum was heavily contaminated with pathogenic Escherichia coli. It is worth noting a great health risk of accidental exposure to pathogenically contaminated wastewater improperly discharged in and around urban slums. The distinct difference in pathotypes between wastewater and drinking water and the significantly smaller positive proportion of the human-specific E. coli genetic biomarker (H8) in drinking water indicate that drinking water contamination could be derived from not only human but also other sources. This highlights that pathotyping in association with the H8 marker provides an indication of pathogen contamination sources of environmental transmission media.
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Agua Potable/microbiología , Escherichia coli Enterotoxigénica/aislamiento & purificación , Escherichia coli Enterotoxigénica/patogenicidad , Áreas de Pobreza , Aguas Residuales/microbiología , Bangladesh , Escherichia coli Enterotoxigénica/clasificación , Infecciones por Escherichia coli/microbiología , Humanos , Tipificación Molecular , Reacción en Cadena de la Polimerasa Multiplex , Toxina Shiga/biosíntesis , Virulencia , Microbiología del Agua , Contaminación del AguaRESUMEN
From expert percussionists to individuals who cannot dance, there are widespread differences in people's abilities to perceive and synchronize with a musical beat. The aim of our study was to identify candidate brain regions that might be associated with these abilities. For this purpose, we used Voxel-Based-Morphometry to correlate inter-individual differences in performance on the Harvard Beat Assessment Tests (H-BAT) with local inter-individual variations in gray matter volumes across the entire brain space in 60 individuals. Analysis revealed significant co-variations between performances on two perceptual tasks of the Harvard Beat Assessment Tests associated with beat interval change discrimination (faster, slower) and gray matter volume variations in the cerebellum. Participant discrimination thresholds for the Beat Finding Interval Test (quarter note beat) were positively associated with gray matter volume variation in cerebellum lobule IX in the left hemisphere and crus I bilaterally. Discrimination thresholds for the Beat Interval Test (simple series of tones) revealed the tendency for a positive association with gray matter volume variations in crus I/II of the left cerebellum. Our results demonstrate the importance of the cerebellum in beat interval discrimination skills, as measured by two perceptual tasks of the Harvard Beat Assessment Tests. Current findings, in combination with evidence from patients with cerebellar degeneration and expert dancers, suggest that cerebellar gray matter and overall cerebellar integrity are important for temporal discrimination abilities.
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Cerebelo/fisiología , Baile/fisiología , Música , Desempeño Psicomotor/fisiología , Adulto , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Micrometer-sized monodisperse polystyrene (PS) particles carrying a pH-responsive poly[2-(diethylamino)ethyl methacrylate] (PDEA) colloidal stabilizer were synthesized via free radical dispersion polymerization. X-ray photoelectron spectroscopy and electrophoretic measurements verified that PDEA covered the PS particle surface. At pH 3.0 and 6.3, where the PDEA is protonated and cationically charged, the PDEA-PS particles were well dispersed in aqueous media thanks to the water soluble PDEA stabilizer and slowly sedimented due to gravity and enriched at the bottom of the glass vials. At pH 10.0, where the PDEA is non-protonated and neutral, the PDEA-PS particles weakly aggregated due to non-hydrated and collapsed PDEA. These PDEA-PS particles and aggregates sedimented to the bottom. The sediment height observed at pH 10.0 was higher than those observed at pH 3.0 and 6.3 in both wet and dry systems, which indicated that a larger porosity was formed at pH 10.0. Mechanical testing experiments confirmed that the fracture toughness of the dried materials decreased with an increase of pH. The fracture toughness was found to be correlated with the degree of particle ordering in the dried particulate materials: more ordered, dense packings lead to a higher fracture toughness compared to amorphous, less dense packings. Thus, we could tune fracture toughness and degree of particle ordering by controlling the pH.
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The electronic and magnetic properties of chemically modified graphene armchair edges are studied using a combination of tight-binding calculations, first-principles modelling, and low temperature scanning tunneling microscopy (STM) experiments. The atomically resolved STM images of the hydrogen etched graphitic edges suggest the presence of localized states at the Fermi level for certain armchair edges. We demonstrate theoretically that the topological zero-energy edge mode may emerge at armchair boundaries with asymmetrical chemical termination of the two outermost atoms in the unit cell. We particularly focus our attention on armchair edges terminated by various combinations of the hydrogen (H, H2) and methylene (CH2) groups. The inclusion of the spin component in our calculations reveals the appearance of π-electron-based magnetism at the armchair edges under consideration.
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BACKGROUND: The efficacy and safety of single-incision laparoscopic colectomy (SILC) for colonic cancer remain unclear. The aim of this study was to determine the outcomes of SILC compared with multiport laparoscopic colectomy (MPLC) for colonic cancer. METHODS: Patients with histologically proven colonic carcinoma located in the caecum, ascending, sigmoid or rectosigmoid colon, clinically diagnosed as stage 0-III by CT, were eligible for this study. Patients were randomized before surgery and underwent tumour dissection with complete mesocolic excision. Safety analyses were conducted according to randomization groups. RESULTS: A total of 200 patients were enrolled and randomized to the MPLC (100 patients) or SILC (100 patients) arm. Surgical outcomes were similar between the MPLC and SILC arms, including duration of operation (mean 162 versus 156 min respectively; P = 0·273), blood loss (mean 8·8 versus 21·4 ml; P = 0·102), conversion to open laparotomy (2·0 versus 1·0 per cent; P = 0·561), reoperation (3·0 versus 3·0 per cent; P = 1·000), time to first flatus (both median 1 day; P = 0·155) and postoperative hospital stay (both median 6; P = 0·372). The total skin incision length was significantly shorter in the SILC arm (mean 4·4 cm versus 6·8 cm in the MPLC arm; P < 0·001). The median duration of analgesia use was 5 days in the MPLC and 4 days in the SILC arm (P = 0·485). Overall complication rates were equivalent (15·0 versus 12·0 per cent respecitvely; P = 0·680). CONCLUSION: SILC is not superior to MPLC. REGISTRATION NUMBER: UMIN000007220 (http://www.umin.ac.jp/ctr/index.htm).
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Adenocarcinoma/cirugía , Colectomía/métodos , Neoplasias del Colon/cirugía , Laparoscopía/métodos , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Resultado del TratamientoRESUMEN
Submicrometer-sized polystyrene (PS) particles carrying stimuli-responsive poly[2-(diethylamino)ethyl methacrylate] (PDEA) hairs with degrees of polymerization of 30, 60 and 90 were synthesized by dispersion polymerization and used as a particulate foam stabilizer. The effects of the composition of these PDEA-PS particles and foam formation conditions on foamability, foam stability and foam microstructures were extensively investigated. The hairy particles were found to work as an effective stabilizer of aqueous foams in basic media, in which the PDEA hairs are not protonated and thus the particle surfaces exhibit suitable wettability at the air-water interface. In contrast, little to no foam or unstable foams were formed in acidic aqueous media, in which the hairs are protonated and are therefore water soluble. Particles carrying longer hairs resulted in greater foamability and more highly stabilized foams that were capable of persisting for more than one month. Foams were found to form in a narrower pH range when using PS particles with longer hairs, due to both entropic and image charge effects. Data obtained from the touch mixer mixing method showed that both foamability and foam stability increased with increases in the concentration of polymer particles up to 10 wt%, because higher concentrations allowed greater air-water interfacial areas to be stabilized. Conversely, only minimal foam was obtained at and above 15 wt% because of the high viscosity of the resulting aqueous particle dispersion. Trials using the homogenizer mixing method showed that foam with a cream-like texture could be formed even at 40 wt% particle concentration as a result of the improved mixing efficiency. Defoamation could be induced by exposing the foams to HCl vapor. Exposure to acidic vapor led to in situ protonation of the 2-(diethylamino)ethyl methacrylate residues, rendering the PDEA hairs hydrophilic and water soluble, and desorption of the PDEA-PS particles from the air-water interface.
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We have investigated 4-µm-band SO3 absorption lines for in situSO3 detection using a mid-infrared laser source based on difference frequency generation in a quasi-phase-matched LiNbO3 waveguide. In the wavelength range of 4.09400-4.10600 µm, there were strong SO3 absorption lines. The maximum absorption coefficient at a concentration of 170 ppmv was estimated to be about 3.2×10-5 cm-1 at a gas temperature of 190°C. In coexistence with H2O, the reduction of the SO3 absorption peak height was observed, which was caused by sulfuric acid formation. We discuss a method of using an SO3 equilibrium curve to derive the total SO3 molecule concentration.
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Characteristics of waste and wastewater management can affect material flows. Our research investigates the management of waste and wastewater in urban areas of developing countries and its effects on phosphorus flow based on a case study in Hue Citadel, Hue, Vietnam. One hundred households were interviewed to gain insight into domestic waste and wastewater management together with secondary data collection. Next, a phosphorus flow model was developed to quantify the phosphorus input and output in the area. The results showed that almost all wastewater generated in Hue Citadel was eventually discharged into water bodies and to the ground/groundwater. This led to most of the phosphorus output flowing into water bodies (41.2 kg P/(ha year)) and ground/groundwater (25.3 kg P/(ha year)). Sewage from the sewer system was the largest source of phosphorus loading into water bodies, while effluent from on-site sanitation systems was responsible for a major portion of phosphorus into the ground/groundwater. This elevated phosphorus loading is a serious issue in considering surface water and groundwater protection.
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Modelos Teóricos , Fósforo/análisis , Administración de Residuos , Agua Subterránea , Saneamiento , Aguas del Alcantarillado , Vietnam , Aguas Residuales/análisisRESUMEN
Submicrometer-sized polystyrene (PS) particles carrying poly[2-(diethylamino)ethyl methacrylate] (PDEA) hairs (PDEA-PS particles) were synthesized by free radical dispersion polymerization. The hydrophilicity-hydrophobicity balance of the PDEA could be tuned by varying the temperature at near neutral pH (a lower critical solution temperature of PDEA at pH 6.86, 41 °C) and therefore these sterically-stabilized particles acted as temperature-sensitive stabilizers for aqueous foams. At 25 °C, where the PDEA hairs were hydrated and PDEA-PS particles were colloidally stable in aqueous media, foams were formed which coalesced with time and the size of the bubble increased. At 40 and 45 °C, where the PDEA hairs were partially non-hydrated and PDEA-PS particles were close to flocculation or weakly flocculated, foams were formed and bubble coalescence and size increase speeds were slower than those observed at 25 °C. At and above 50 °C, where the PDEA hairs were non-hydrated and PDEA-PS particles were heavily flocculated in aqueous media, the more stable cream-like foams whose volume was almost the same for 1 week were formed. Scanning electron microscopy studies indicated that the particles mainly adsorbed at the air-water interface as monolayers at 25 °C and as multilayers at and above 40 °C. The foam stability and structure could be controlled by changing the temperature.
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AIM: The indications for intersphincteric (ISR) anterior resection are not clearly defined. The aim of this study was to evaluate vertical extension of T2 or T3 low rectal cancer treated by rectal amputation to optimize patient selection for ISR. METHOD: The abdominoperineal excision specimens of T2 or T3 low rectal cancer from 53 patients treated between 1992 and 2004 were retrospectively reviewed. Vertical invasion was quantified by measuring the shortest distance between the tumour and the striated muscle (T-SM), assuming that this represented the surgical margin that would have be achieved had an ISR been performed. RESULTS: Involvement of the dentate line (DL) and intramural distal spread were independent risk factors for T-SM ≤ 2 mm. The T-SM was less when the inferior border of the tumour was on the distal side of the DL (r = 0.572, P < 0.001). The probability of involvement of the DL, intramural distal spread or either one of these being associated with T-SM ≤ 2 mm was 43, 46 and 43%, respectively. All patients without both intramural distal spread and involvement of the DL had T-SM > 2. CONCLUSION: We recommend that ISR should only be performed for patients with T2 or T3 low rectal cancer in whom the lowest edge of the tumour is above the DL and there is no intramural distal spread. Such patients are relatively unlikely to have a T-SM ≤ 2 mm.
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Canal Anal/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Selección de Paciente , Diafragma Pélvico/patología , Neoplasias del Recto/cirugía , Anciano , Canal Anal/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Diafragma Pélvico/cirugía , Neoplasias del Recto/patología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND/AIMS: Anastomotic leakage is major complication of colorectal surgery. Total parenteral nutrition (TPN) and fasting are conservative treatments for leakage in the absence of peritonitis in Japan. Elemental diet (ED) jelly is a completely digested formula and is easily absorbed without secretion of digestive juices. The purpose of this study was to assess the safety of ED jelly in management of anastomotic leakage. METHODOLOGY: Six hundred and two patients who underwent elective surgery for left side colorectal cancer from January 2008 to December 2011 were included in the study. Pelvic drainage was performed for all patients. Sixty-three (10.5%) patients were diagnosed with an anastomotic leakage, and of these, 31 (5.2%) without diverting stoma were enrolled in this study. RESULTS: Sixteen patients received TPN (TPN group) and 15 patients received ED jelly (ED group). The duration of intravenous infusion was significantly shorter in the ED group than in the TPN group (15 days versus 25 days, P= 0.008). In the TPN group, catheter infection was occurred in 2 patients who required re-insertion of the catheter. CONCLUSION: Conservative management of anastomotic leakage after colorectal surgery with ED jelly appears to be a safe and useful approach.
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Fuga Anastomótica/terapia , Colectomía/efectos adversos , Neoplasias Colorrectales/cirugía , Alimentos Formulados , Nutrición Parenteral Total , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Fuga Anastomótica/diagnóstico , Fuga Anastomótica/dietoterapia , Fuga Anastomótica/etiología , Procedimientos Quirúrgicos Electivos , Femenino , Alimentos Formulados/efectos adversos , Geles , Humanos , Masculino , Persona de Mediana Edad , Nutrición Parenteral Total/efectos adversos , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Rapid socio-economic development in suburban areas of developing countries has induced changes in agricultural waste and nutrient management, resulting in water pollution. The study aimed at estimating agricultural nutrient cycles and their contribution to the water environment. A material flow model of nitrogen (N) and phosphorus (P) was developed focusing on agricultural activities from 1980 to 2010 in Trai hamlet, an agricultural watershed in Nhue-Day River basin, Vietnam. The model focused on the change in household management of human excreta and livestock excreta, and chemical fertilizer consumption. The results showed that the proportion of nutrients from compost/manure applied to paddy fields decreased from 85 to 41% for both N and P between 1980 and 2010. The nutrient inputs derived from chemical fertilizer decreased 6% between 1980 and 2000 for both N and P. Then, these nutrients increased 1.4 times for N and 1.2 times for P from 2000 to 2010. As of 2010, the total inputs to paddy fields have amounted to 435 kg-N/ha/year and 90 kg-P/ha/year. Of these nutrient inputs, 40% of N and 65% of P were derived from chemical fertilizer. Thirty per cent (30%) of total N input was discharged to the water bodies through agricultural runoff and 47% of total P input accumulated in soil.
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Agricultura , Monitoreo del Ambiente/métodos , Fertilizantes/análisis , Ríos/química , Contaminantes Químicos del Agua/análisis , Agricultura/normas , Humanos , Estiércol/análisis , Modelos Teóricos , Nitrógeno/análisis , Fósforo/análisis , Suelo/normas , VietnamRESUMEN
Sphingosine kinase 1 (SPHK1) overexpression in malignant cells has been reported. Mouse Friend cells showed higher SPHK1 but not SPHK2 expression compared with other mouse cell lines. A Sphk1 promoter analysis demonstrated the region between -53bp and the first exon as the minimal promoter. Further promoter truncation revealed the importance of a MYB-binding site. EMSA using this region as the probe demonstrated one band containing c-MYB protein, and its intensity decreased during erythroid differentiation with hexamethylane bisacetamide (HMBA), a potent inducer of erythroid differentiation of Friend cells. ChIP assay also revealed in vivo binding of c-MYB. c-MYB overexpression and siRNA for c-Myb affected SPHK1 expression, confirming the important regulatory role of c-MYB in SPHK1 expression. HMBA reduced c-MYB expression rapidly. Induced differentiation by HMBA caused a marked and rapid reduction of SPHK1 mRNA, protein and enzyme activity leading to the rapid decrease of cellular sphingosine 1-phosphate level. Moreover, terminally differentiated cells did not resume SPHK1 expression. Compared with original Friend cells, stable overexpression of wild-type SPHK1 showed higher cell proliferation, resistance to cell death by serum depletion. Interestingly, HMBA-induced differentiation of these cells was delayed but not completely suppressed. In contrast, SPHK inhibitor and its siRNA inhibited cell growth and enhanced HMBA-induced differentiation significantly, suggesting that SPHK1 delayed HMBA-induced differentiation by its cell proliferation-promoting activity. Effects of pertussis toxin, a G-protein-coupled receptor inhibitor, and S1P receptor antagonist on Friend cell growth and differentiation were negligible, suggesting the importance of the intracellular SPHK1/S1P signaling in Friend cells.
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Diferenciación Celular/genética , Fosfotransferasas (Aceptor de Grupo Alcohol) , Proteínas Proto-Oncogénicas c-myb , Receptores de Lisoesfingolípidos , Animales , Línea Celular , Regulación hacia Abajo , Humanos , Ratones , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas c-myb/genética , Proteínas Proto-Oncogénicas c-myb/metabolismo , ARN Mensajero/genética , ARN Interferente Pequeño , Receptores de Lisoesfingolípidos/antagonistas & inhibidores , Receptores de Lisoesfingolípidos/genética , Receptores de Lisoesfingolípidos/metabolismo , Transducción de SeñalRESUMEN
BACKGROUND: CD133 and CD44 are putative cancer stem cell (CSC) markers in colorectal cancer (CRC). However, their clinical significance is currently unclear. Here, we evaluated primary CRC cell isolates to determine the significance of several CSC markers, including CD133 and CD44, as predictors of tumourigenesis and prognosis. METHODS: CD133- and CD44-positive cells from fresh clinical samples of 77 CRCs were selected by flow cytometric sorting and evaluated for tumourigenicity following subcutaneous transplantation into NOD/SCID mice. Cancer stem cell marker expression was examined in both xenografts and a complementary DNA library compiled from 167 CRC patient samples. RESULTS: CD44(+), CD133(+) and CD133(+)CD44(+) sub-populations were significantly more tumourigenic than the total cell population. The clinical samples expressed several transcript variants of CD44. Variant 2 was specifically overexpressed in both primary tumours and xenografts in comparison with the normal mucosa. A prognostic assay using qRT-PCR showed that the CD44v2(high) group (n=84, 5-year survival rate (5-OS): 0.74) had a significantly worse prognosis (P=0.041) than the CD44v2(low) group (n=83, 5-OS: 0.88). CONCLUSIONS: CD44 is an important CSC marker in CRC patients. Furthermore, CRC patients with high expression of CD44v2 have a poorer prognosis than patients with other CD44 variants.