Generation and characterization of two immortalized human osteoblastic cell lines useful for epigenetic studies

Different model systems using osteoblastic cell lines have been developed to help understand the process of bone formation. Here, we report the establishment of two human osteoblastic cell lines obtained from primary cultures upon transduction of immortalizing genes. The resulting cell lines had no major differences to their parental lines in their gene expression profiles. Similar to primary osteoblastic cells, osteocalcin transcription increased following 1,25-dihydroxyvitamin D3 treatment and the immortalized cells formed a mineralized matrix, as detected by Alizarin Red staining. Moreover, these human cell lines responded by upregulating ALPL gene expression after treatment with the demethylating agent 5-aza-2 Œ-deoxycytidine (AzadC), as shown before for primary osteoblasts. We further demonstrate that these cell lines can differentiate in vivo, using a hydroxyapatite/tricalcium phosphate composite as a scaffold, to produce bone matrix. More importantly, we show that these cells respond to demethylating treatment, as shown by the increase in SOST mRNA levels, the gene encoding sclerostin, upon treatment of the recipient mice with AzadC. This also confirms, in vivo, the role of DNA methylation in the regulation of SOST expression previously shown in vitro. Altogether our results show that these immortalized cell lines constitute a particularly useful model system to obtain further insight into bone homeostasis, and particularly into the epigenetic mechanisms regulating sclerostin production

La fomación farmacéutica mediante el modelo de enseñanza-aprendizaje por Objetos de Transformación (Problem-Based Learning)

El modelo de enseñanza-aprendizaje mediante problemas de la práctica profesional, conocido internacionalmentecomo Problems Based Learning (PBL) está siendo introducido con éxito en universidades europeas y norteamericanas.Este modelo educativo ha tenido un especial desarrollo en el plan de estudios de la licenciatura en Farmacia(Química Farmacéutica Biológica) de la Universidad Autónoma Metropolitana-Xochimilco de México, donde se tieneuna experiencia positiva de 25 años, denominándosele enseñanza-aprendizaje mediante Objetos de Transformacióno enseñanza modular

La fomación farmacéutica mediante el modelo de enseñanza-aprendizaje por Objetos de Transformación (Problem-Based Learning)

El modelo de enseñanza-aprendizaje mediante problemas de la práctica profesional, conocido internacionalmentecomo Problems Based Learning (PBL) está siendo introducido con éxito en universidades europeas y norteamericanas.Este modelo educativo ha tenido un especial desarrollo en el plan de estudios de la licenciatura en Farmacia(Química Farmacéutica Biológica) de la Universidad Autónoma Metropolitana-Xochimilco de México, donde se tieneuna experiencia positiva de 25 años, denominándosele enseñanza-aprendizaje mediante Objetos de Transformacióno enseñanza modular

Solving the mu problem with a heavy Higgs boson

We discuss the generation of the mu-term in a class of supersymmetric models characterized by a low energy effective superpotential containing a term lambda S H_1 H_2 with a large coupling lambda~2. These models generically predict a lightest Higgs boson well above the LEP limit of 114 GeV and have been shown to be compatible with the unification of gauge couplings. Here we discuss a specific example where the superpotential has no dimensionful parameters and we point out the relation between the generated mu-term and the mass of the lightest Higgs boson. We discuss the fine-tuning of the model and we find that the generation of a phenomenologically viable mu-term fits very well with a heavy lightest Higgs boson and a low degree of fine-tuning. We discuss experimental constraints from collider direct searches, precision data, thermal relic dark matter abundance, and WIMP searches finding that the most natural region of the parameter space is still allowed by current experiments. We analyse bounds on the masses of the superpartners coming from Naturalness arguments and discuss the main signatures of the model for the LHC and future WIMP searches.Comment: Extended discussion of the LHC phenomenology, as published on JHEP plus an addendum on the existence of further extremal points of the potential. 47 pages, 16 figure

Spirometry-adjusted fraction of exhaled nitric oxide increases accuracy for assessment of asthma control in children

Spirometry and exhaled nitric oxide are two important complimentary tools to identify and assess asthma control in children. We aimed to determine the ability of a new suggested spirometry-adjusted fraction of exhaled nitric oxide (NO) index in doing that. A random sample of 1602 schoolchildren were screened by a health questionnaire, skin prick tests, spirometry with bronchodilation and exhaled NO. A total of 662 children were included with median (IQR) exhaled NO 11(14) ppb. Receiver operating characteristic (ROC) curves using exhaled NO equations from Malmberg, Kovesi and Buchvald, and spirometry-adjusted fraction of exhaled NO values were applied to identify asthmatic children and uncontrolled asthma. Receiver operating characteristic (ROC) curves failed to identify asthmatic children (all AUC < 0.700). Spirometry-adjusted fraction of exhaled NO/FEV1 (AUC = 0.712; P = .010) and NO/FEF25%-75% (AUC = 0.735 P = .004) had a fair and increased ability to identify uncontrolled disease compared with exhaled NO (AUC = 0.707; P = .011) or the Malmberg equation (AUC = 0.701; P = .014). Sensitivity and specificity identifying non-controlled asthma were 59% and 81%, respectively, for the cut-off value of 9.7 ppb/L for exhaled NO/FEV1 , and 40% and 100% for 15.7 ppb/L/s for exhaled NO/FEF25%-75% . Exhaled NO did not allow to identify childhood asthma. Spirometry-adjusted fraction of exhaled NO performed better-assessing asthma control in children. Thus, although more validation studies are needed, we suggest its use in epidemiological studies to assess asthma control.Health, Comfort and Energy in the Built Environment (HEBE), Grant/Award Number: NORTE-01-0145-FEDER-000010; Programa Operacional Regional do Norte, Grant/Award Number: NORTE2020; Fundo Europeu de Desenvolvimento Regional (FEDER); Foundation for Science and Technology schoolarships, Grant/Award Number: SFRH/BD/108605/2015 and SFRH/BD/112269/201

Using fractional exhaled nitric oxide (FeNO) to diagnose steroid-responsive disease and guide asthma management in routine care

Acknowledgements We thank Robin Taylor for his informative thinking and publications on FeNO, which have helped to influence and direct the thinking of the authors. Funding Extraction of the real-life dataset was funded by Research in Real Life Limited, the analysis of the dataset and the writing of this manuscript were co-funded (50:50) by Research in Real Life Limited and Aerocrine.Peer reviewedPublisher PD

Тактика ведения пациентов при синдроме Мэллори-Вейсса

МЭЛЛОРИ-ВЕЙСА СИНДРОМ /диагн /терПИЩЕВОДА ПЕРФОРАЦИЯ /диагн /терЖЕЛУДОЧНО-КИШЕЧНОЕ КРОВОТЕЧЕНИЕГЕМОСТАЗ ЭНДОСКОПИЧЕСКИ

A precision study of the fine tuning in the DiracNMSSM

Recently the DiracNMSSM has been proposed as a possible solution to reduce the fine tuning in supersymmetry. We determine the degree of fine tuning needed in the DiracNMSSM with and without non-universal gaugino masses and compare it with the fine tuning in the GNMSSM. To apply reasonable cuts on the allowed parameter regions we perform a precise calculation of the Higgs mass. In addition, we include the limits from direct SUSY searches and dark matter abundance. We find that both models are comparable in terms of fine tuning, with the minimal fine tuning in the GNMSSM slightly smaller.Comment: 20 pages + appendices, 10 figure