Effect of silver nanoparticles on human mesenchymal stem cell differentiation

PubMed Central

Diendorf, Jörg; Epple, Matthias; Schildhauer, Thomas A; Köller, Manfred

2014-01-01

Summary Background: Silver nanoparticles (Ag-NP) are one of the fastest growing products in nano-medicine due to their enhanced antibacterial activity at the nanoscale level. In biomedicine, hundreds of products have been coated with Ag-NP. For example, various medical devices include silver, such as surgical instruments, bone implants and wound dressings. After the degradation of these materials, or depending on the coating technique, silver in nanoparticle or ion form can be released and may come into close contact with tissues and cells. Despite incorporation of Ag-NP as an antibacterial agent in different products, the toxicological and biological effects of silver in the human body after long-term and low-concentration exposure are not well understood. In the current study, we investigated the effects of both ionic and nanoparticulate silver on the differentiation of human mesenchymal stem cells (hMSCs) into adipogenic, osteogenic and chondrogenic lineages and on the secretion of the respective differentiation markers adiponectin, osteocalcin and aggrecan. Results: As shown through laser scanning microscopy, Ag-NP with a size of 80 nm (hydrodynamic diameter) were taken up into hMSCs as nanoparticulate material. After 24 h of incubation, these Ag-NP were mainly found in the endo-lysosomal cell compartment as agglomerated material. Cytotoxicity was observed for differentiated or undifferentiated hMSCs treated with high silver concentrations (≥20 µg·mL−1 Ag-NP; ≥1.5 µg·mL−1 Ag+ ions) but not with low-concentration treatments (≤10 µg·mL−1 Ag-NP; ≤1.0 µg·mL−1 Ag+ ions). Subtoxic concentrations of Ag-NP and Ag+ ions impaired the adipogenic and osteogenic differentiation of hMSCs in a concentration-dependent manner, whereas chondrogenic differentiation was unaffected after 21 d of incubation. In contrast to aggrecan, the inhibitory effect of adipogenic and osteogenic differentiation was confirmed by a decrease in the secretion of specific

[Intestinal cleaning for colonoscopy in children: effectiveness, adherence and adverse effects of schemes differentiated by age].

PubMed

Miquel, Isabel; Arancibia, María Eugenia; Alliende, Francisco; Ríos, Gloria; Rodríguez, Lorena; Lucero, Yalda; Saelzer, Eric

2017-04-01

Adequate intestinal cleanliness is crucial to achieve optimal colonoscopy performance. Several bowel preparation (BP) schemes have been proposed, but there is still no consensus as regards which is the most suitable in paediatric patients. To describe the effectiveness, adherence, and adverse effects of BP protocols differentiated by age group in paediatric patients subjected to colonoscopy. Prospective, study that included patients < 18 years subjected to colonoscopy. BP protocols differentiated by age group were indicated as follows: < 6 m (glycerine suppository); 6 m-3y 11 m (poly-ethylene-glycol (PEG 3350 without electrolytes); 4y-9y 11 m (PEG 3350 without electrolytes + bisacodyl); 10 y-18 y (PEG 3350 with electrolytes). Demographic, clinical information, adherence and adverse effects were registered. Effectiveness was determined using a validated scale (Boston modified) during colonoscopy. A total of 159 patients were included, of which 87 (55%) were males, and with a median age of 4 years (range 1 m-17 years). Seventy eight percent of patients achieved successful BP. The higher effectiveness was observed in the groups of < 6 m (96%) and 10-18 y (91%). Constipation was significantly more frequent (29%) in the 4 yo-9 yo 11 m in which lower effectiveness was observed (69%). Good adherence was observed in 87% of patients. Adverse effects were observed in a third of patients, although they were mild and did not lead to the suspension of the BP. Satisfactory results were achieved with the BP schemes used, with a successful BP being obtained in 4 out of 5 patients. Results were different between groups, which is probably related to previous bowel transit and indicated medication.

Use of a Differential Observing Response to Expand Restricted Stimulus Control

ERIC Educational Resources Information Center

Walpole, Carrie Wallace; Roscoe, Eileen M.; Dube, William V.

2007-01-01

This study extends previous work on the use of differential observing responses (DOR) to remediate atypically restricted stimulus control. A participant with autism had high matching-to-sample accuracy scores with printed words that had no letters in common (e.g., "cat," "lid," "bug") but poor accuracy with words that had two letters in common…

Differentiated Storytelling: From Focused Observation to Strategic Teaching

ERIC Educational Resources Information Center

Abilock, Debbie, Ed.

2008-01-01

Differentiated teaching focuses on the student--the varying needs, interests and abilities in the classroom--in order to design curriculum which results in student understanding through application. Some differentiation implementations are little more than tweaks, but if one is ambitious, differentiation modifications can require substantial time…

Rethinking Differentiation--Using Teachers' Time Most Effectively

ERIC Educational Resources Information Center

Marshall, Kim

2016-01-01

The goals of differentiation are laudable, but in recent years, many question whether it is really possible for a teacher to tailor instruction for 20 to 30 different students and whether it's desirable to differentiate by learning styles. Differentiation is just one factor in effective instruction. Supervisors who walk into a classroom looking…

Differential effects of an adult observer's presence on sex-typed play behavior: A comparison between gender-schematic and gender-aschematic preschool children.

PubMed

Wilansky-Traynor, Pamela; Lobel, Thalma E

2008-08-01

The present study examined the differential effect of an adult observer's presence on the sex-typed play behavior of gender schematic and aschematic preschoolers. A total of 116 Israeli preschoolers (M age = 64.9 months) participated in the study. Children were classified as either gender schematic or aschematic based upon responses to a computerized measure of different sex stereotype components. Children's play behavior with gender typical and atypical, attractive and unattractive, toys was videotaped. An observer was present for half the children's play and absent for the other half's play. Observation status affected the aschematic, but not the schematic, children's play with gender typical toys. For example, observed aschematic boys spent a greater percent of time playing with the unattractive masculine toys compared to unobserved aschematic boys. This difference was not apparent for schematic boys. Additionally, a difference found for schematic boys was not apparent in schematic girls, i.e., when unobserved, schematic boys tended to spend a greater percent of time playing with the unattractive masculine toy than aschematic boys. Further, some differences were found for unattractive, and not attractive, toys. For instance, observed aschematic boys spent a greater percent of time playing with the unattractive masculine toy than did the unobserved aschematic boys. This gap was not found for the attractive masculine toy. Results are discussed with reference to the accessibility and complexity of gender schemas.

The Warburg effect: persistence of stem-cell metabolism in cancers as a failure of differentiation.

PubMed

Riester, M; Xu, Q; Moreira, A; Zheng, J; Michor, F; Downey, R J

2018-01-01

Two recent observations regarding the Warburg effect are that (i) the metabolism of stem cells is constitutive (aerobic) glycolysis while normal cellular differentiation involves a transition to oxidative phosphorylation and (ii) the degree of glucose uptake of a malignancy as imaged by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is associated with histologic measures of tumor differentiation. Combining these observations, we hypothesized that the high levels of glucose uptake observed in poorly differentiated cancers may reflect persistence of the glycolytic metabolism of stem cells in malignant cells that fail to fully differentiate. Tumor glucose uptake was measured by FDG-PET in 552 patients with histologically diverse cancers. We used normal mixture modeling to explore FDG-PET standardized uptake value (SUV) distributions and tested for associations between glucose uptake and histological differentiation, risk of lymph node metastasis, and survival. Using RNA-seq data, we carried out pathway and transcription factor analyses to compare tumors with high and low levels of glucose uptake. We found that well-differentiated tumors had low FDG uptake, while moderately and poorly differentiated tumors had higher uptake. The distribution of SUV for each histology was bimodal, with a low peak around SUV 2-5 and a high peak at SUV 8-14. The cancers in the two modes were clinically distinct in terms of the risk of nodal metastases and death. Carbohydrate metabolism and the pentose-related pathway were elevated in the poorly differentiated/high SUV clusters. Embryonic stem cell-related signatures were activated in poorly differentiated/high SUV clusters. Our findings support the hypothesis that the biological basis for the Warburg effect is a persistence of stem cell metabolism (i.e. aerobic glycolysis) in cancers as a failure to transition from glycolysis-utilizing undifferentiated cells to oxidative phosphorylation-utilizing differentiated cells. We

New Interview and Observation Measures of the Broader Autism Phenotype: Group Differentiation

ERIC Educational Resources Information Center

de Jonge, Maretha; Parr, Jeremy; Rutter, Michael; Wallace, Simon; Kemner, Chantal; Bailey, Anthony; van Engeland, Herman; Pickles, Andrew

2015-01-01

To identify the broader autism phenotype (BAP), the Family History Interview subject and informant versions and an observational tool (Impression of Interviewee), were developed. This study investigated whether the instruments differentiated between parents of children with autism, and parents of children with Down syndrome (DS). The BAP scores of…

Cytotoxicity and inhibitory effects of low-concentration triclosan on adipogenic differentiation of human mesenchymal stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Li-Wu; Wu, Qiangen; Green, Bridgett

2012-07-15

Humans at all ages are continually exposed to triclosan (TCS), a widely used antimicrobial agent that can be found in many daily hygiene products, such as toothpastes and shampoos; however, the toxicological and biological effects of TCS in the human body after long-term and low-concentration exposure are far from being well understood. In the current study, we investigated the effects of TCS on the differentiation of human mesenchymal stem cells (hMSCs) by measuring the cytotoxicity, morphological changes, lipid accumulation, and the expression of adipocyte differentiation biomarkers during 21-day adipogenesis. Significant cytotoxicity was observed in un-induced hMSCs treated with high-concentration TCSmore » (≥ 5.0 μM TCS), but not with low-concentration treatments (≤ 2.5 μM TCS). TCS inhibited adipocyte differentiation of hMSCs in a concentration-dependent manner in the 0.156 to 2.5 μM range as indicated by morphological changes with Oil Red O staining, which is an index of lipid accumulation. The inhibitory effect was confirmed by a decrease in gene expression of specific adipocyte differentiation biomarkers including adipocyte protein 2, lipoprotein lipase, and adiponectin. Our study demonstrates that TCS inhibits adipocyte differentiation of hMSCs under concentrations that are not cytotoxic and in the range observed in human blood. -- Highlights: ► TCS is cytotoxic to un-induced hMSCs at concentrations ≥ 5.0 μM. ► TCS at concentrations ≤ 2.5 μM is not cytotoxic to induced hMSCs. ► TCS at non-cytotoxic concentrations inhibits lipid formation in induced hMSCs. ► TCS decreases the expression of specific biomarkers of adipocyte differentiation. ► TCS at concentrations observed in human blood inhibits adipogenesis of hMSCs.« less

Clinical observation on effect of scalp electroacupuncture for mild cognitive impairment.

PubMed

Zhang, Hong; Zhao, Ling; Yang, Sha; Chen, Zhigang; Li, Yingkun; Peng, Xiaohong; Yang, Yulong; Zhu, Manjia

2013-02-01

To evaluate the therapeutic effect of scalp electroacupuncture for mild cognitive impairment (MCI) in the early stage. Two hundred and thirty three MCI patients were randomly divided into three groups: the drug group, the scalp electroacupuncture group, and the syndrome differentiation group. For the scalp electroacupuncture group, the points of Baihui (DU 20), Sishecong (EX-HN1), Fengchi (GB 20), and Shenting (DU 24) were selected. For the syndrome differentiation group, specific acupoints were added on the basis of syndrome differentiation and according to the scale for the differentiation of syndromes in vascular dementia (SDSVD) beside the acupoints used in the scalp electroacupuncture group. For the drug group, nimodipine was orally administered. Each patient was treated for two courses, eight weeks. The score differences in mini-mental state examination (MMSE), picture recognition, and clock drawing test were observed before and after the treatment. After treatment, the score differences in MMSE and clock drawing test were of obvious statistical significance among three groups (P < 0.01, P < 0.05). The score differences in picture recognition were of extremely statistical significance between the scalp electroacupuncture group and the syndrome differentiation group (P < 0.01), while the difference was not found in the drug group (P > 0.05). There were statistical significant differences in therapeutic effects between the scalp electroacupuncture group and the drug group, and between the syndrome differentiation group and the drug group (P < 0.05), while no statistical difference was found between scalp electroacupuncture group and the syndrome differentiation group (P > 0.05). All the three therapies may improve the cognitive function of MCI patients. The therapeutic effects in the scalp electroacupuncture and syndrome differentiation groups were basically the same, but superior to nimodipine.

Observation and measurement of negative differential resistance on PtSi Schottky junctions on porous silicon.

PubMed

Banihashemian, Seyedeh Maryam; Hajghassem, Hassan; Erfanian, Alireza; Aliahmadi, Majidreza; Mohtashamifar, Mansor; Mosakazemi, Seyed Mohamadhosein

2010-01-01

Nanosize porous Si is made by two step controlled etching of Si. The first etching step is carried on the Si surface and the second is performed after deposition of 75 Å of platinum on the formed surface. A platinum silicide structure with a size of less than 25 nm is formed on the porous Si surface, as measured with an Atomic Forced Microscope (AFM). Differential resistance curve as a function of voltage in 77 K and 100 K shows a negative differential resistance and indicates the effect of quantum tunneling. In general form, the ratio of maximum to minimum tunneling current (PVR) and the number of peaks in I-V curves reduces by increasing the temperature. However, due to accumulation of carriers behind the potential barrier and superposition of several peaks, it is observed that the PVR increases at 100 K and the maximum PVR at 100 K is 189.6.

The effect of nutritional status on myogenic satellite cell proliferation and differentiation.

PubMed

Powell, D J; McFarland, D C; Cowieson, A J; Muir, W I; Velleman, S G

2013-08-01

Early posthatch satellite cell (SC) mitotic activity is a critical component of muscle development and growth. Satellite cells are stem cells that can be induced by nutrition to follow other cellular developmental pathways. The objective of the current study was to determine the effect of restricting protein synthesis on the proliferation and differentiation of SC, using variable concentrations of Met and Cys to modulate protein synthesis. Broiler pectoralis major SC were cultured and treated with 1 of 6 different Met/Cys concentrations: 60/192, 30/96 (control), 7.5/24, 3/9.6, 1/3.2, or 0/0 mg/L. The effect of Met/Cys concentration on SC proliferation and differentiation was measured, and myonuclear accretion was measured by counting the number of nuclei per myotube during differentiation. The 30/96 mg/L Met/Cys treatment resulted in the highest rate of proliferation compared with all other treatments by 72 h of proliferation (P < 0.05). Differentiation was measured with Met/Cys treatments only during proliferation and the cultures receiving normal differentiation medium (R/N), normal proliferation medium and differentiation medium with variable Met/Cys (N/R), or both proliferation and differentiation receiving variable Met/Cys treatments (R/R). Differentiation responded in a dose-dependent manner to Met/Cys concentration under all 3 of these treatment regimens, with a degree of recovery in the R/N regimen cells following reinstatement of the control medium. Reductions in both proliferation and differentiation were more pronounced as Met/Cys concentrations were further reduced, whereas increased differentiation was observed under the increased Met/Cys concentration treatment when applied during differentiation in the N/R and R/R regimens. The number of nuclei per myotube was significantly decreased in the severely Met/Cys restricted treatments (P < 0.05). These data demonstrate the sensitivity of pectoralis major SC to nutritional availability and the importance of

Effects of Differential Item Functioning on Examinees' Test Performance and Reliability of Test

ERIC Educational Resources Information Center

Lee, Yi-Hsuan; Zhang, Jinming

2017-01-01

Simulations were conducted to examine the effect of differential item functioning (DIF) on measurement consequences such as total scores, item response theory (IRT) ability estimates, and test reliability in terms of the ratio of true-score variance to observed-score variance and the standard error of estimation for the IRT ability parameter. The…

Detectability index of differential phase contrast CT compared with conventional CT: a preliminary channelized Hotelling observer study

NASA Astrophysics Data System (ADS)

Tang, Xiangyang; Yang, Yi; Tang, Shaojie

2013-03-01

Under the framework of model observer with signal and background exactly known (SKE/BKE), we investigate the detectability of differential phase contrast CT compared with that of the conventional attenuation-based CT. Using the channelized Hotelling observer and the radially symmetric difference-of-Gaussians channel template , we investigate the detectability index and its variation over the dimension of object and detector cells. The preliminary data show that the differential phase contrast CT outperforms the conventional attenuation-based CT significantly in the detectability index while both the object to be detected and the cell of detector used for data acquisition are relatively small. However, the differential phase contrast CT's dominance in the detectability index diminishes with increasing dimension of either object or detector cell, and virtually disappears while the dimension of object or detector cell approaches a threshold, respectively. It is hoped that the preliminary data reported in this paper may provide insightful understanding of the differential phase contrast CT's characteristic in the detectability index and its comparison with that of the conventional attenuation-based CT.

Differential absorption lidar observation on small-time-scale features of water vapor in the atmospheric boundary layer

NASA Astrophysics Data System (ADS)

Kong, Wei; Li, Jiatang; Liu, Hao; Chen, Tao; Hong, Guanglie; Shu, Rong

2017-11-01

Observation on small-time-scale features of water vapor density is essential for turbulence, convection and many other fast atmospheric processes study. For the high signal-to-noise signal of elastic signal acquired by differential absorption lidar, it has great potential for all-day water vapor turbulence observation. This paper presents a set of differential absorption lidar at 935nm developed by Shanghai Institute of Technical Physics of the Chinese Academy of Science for water vapor turbulence observation. A case at the midday is presented to demonstrate the daytime observation ability of this system. "Autocovariance method" is used to separate the contribution of water vapor fluctuation from random error. The results show that the relative error is less than 10% at temporal and spatial resolution of 10 seconds and 60 meters in the ABL. This indicate that the system has excellent performance for daytime water vapor turbulence observation.

Observation of negative differential resistance in mesoscopic graphene oxide devices.

PubMed

Rathi, Servin; Lee, Inyeal; Kang, Moonshik; Lim, Dongsuk; Lee, Yoontae; Yamacli, Serhan; Joh, Han-Ik; Kim, Seongsu; Kim, Sang-Woo; Yun, Sun Jin; Choi, Sukwon; Kim, Gil-Ho

2018-05-08

The fractions of various functional groups in graphene oxide (GO) are directly related to its electrical and chemical properties and can be controlled by various reduction methods like thermal, chemical and optical. However, a method with sufficient controllability to regulate the reduction process has been missing. In this work, a hybrid method of thermal and joule heating processes is demonstrated where a progressive control of the ratio of various functional groups can be achieved in a localized area. With this precise control of carbon-oxygen ratio, negative differential resistance (NDR) is observed in the current-voltage characteristics of a two-terminal device in the ambient environment due to charge-activated electrochemical reactions at the GO surface. This experimental observation correlates with the optical and chemical characterizations. This NDR behavior offers new opportunities for the fabrication and application of such novel electronic devices in a wide range of devices applications including switches and oscillators.

Differential effect of extracellular matrix derived from papillary and reticular fibroblasts on epidermal development in vitro.

PubMed

Janson, David; Rietveld, Marion; Mahé, Christian; Saintigny, Gaëlle; El Ghalbzouri, Abdoelwaheb

2017-06-01

Papillary and reticular fibroblasts have different effects on keratinocyte proliferation and differentiation. The aim of this study was to investigate whether these effects are caused by differential secretion of soluble factors or by differential generation of extracellular matrix from papillary and reticular fibroblasts. To study the effect of soluble factors, keratinocyte monolayer cultures were grown in papillary or reticular fibroblast-conditioned medium. To study the effect of extracellular matrix, keratinocytes were grown on papillary or reticular-derived matrix. Conditioned medium from papillary or reticular fibroblasts did not differentially affect keratinocyte viability or epidermal development. However, keratinocyte viability was increased when grown on matrix derived from papillary, compared with reticular, fibroblasts. In addition, the longevity of the epidermis was increased when cultured on papillary fibroblast-derived matrix skin equivalents compared with reticular-derived matrix skin equivalents. The findings indicate that the matrix secreted by papillary and reticular fibroblasts is the main causal factor to account for the differences in keratinocyte growth and viability observed in our study. Differences in response to soluble factors between both populations were less significant. Matrix components specific to the papillary dermis may account for the preferential growth of keratinocytes on papillary dermis.

Evaluating differential effects using regression interactions and regression mixture models

PubMed Central

Van Horn, M. Lee; Jaki, Thomas; Masyn, Katherine; Howe, George; Feaster, Daniel J.; Lamont, Andrea E.; George, Melissa R. W.; Kim, Minjung

2015-01-01

Research increasingly emphasizes understanding differential effects. This paper focuses on understanding regression mixture models, a relatively new statistical methods for assessing differential effects by comparing results to using an interactive term in linear regression. The research questions which each model answers, their formulation, and their assumptions are compared using Monte Carlo simulations and real data analysis. The capabilities of regression mixture models are described and specific issues to be addressed when conducting regression mixtures are proposed. The paper aims to clarify the role that regression mixtures can take in the estimation of differential effects and increase awareness of the benefits and potential pitfalls of this approach. Regression mixture models are shown to be a potentially effective exploratory method for finding differential effects when these effects can be defined by a small number of classes of respondents who share a typical relationship between a predictor and an outcome. It is also shown that the comparison between regression mixture models and interactions becomes substantially more complex as the number of classes increases. It is argued that regression interactions are well suited for direct tests of specific hypotheses about differential effects and regression mixtures provide a useful approach for exploring effect heterogeneity given adequate samples and study design. PMID:26556903

Population stochastic modelling (PSM)--an R package for mixed-effects models based on stochastic differential equations.

PubMed

Klim, Søren; Mortensen, Stig Bousgaard; Kristensen, Niels Rode; Overgaard, Rune Viig; Madsen, Henrik

2009-06-01

The extension from ordinary to stochastic differential equations (SDEs) in pharmacokinetic and pharmacodynamic (PK/PD) modelling is an emerging field and has been motivated in a number of articles [N.R. Kristensen, H. Madsen, S.H. Ingwersen, Using stochastic differential equations for PK/PD model development, J. Pharmacokinet. Pharmacodyn. 32 (February(1)) (2005) 109-141; C.W. Tornøe, R.V. Overgaard, H. Agersø, H.A. Nielsen, H. Madsen, E.N. Jonsson, Stochastic differential equations in NONMEM: implementation, application, and comparison with ordinary differential equations, Pharm. Res. 22 (August(8)) (2005) 1247-1258; R.V. Overgaard, N. Jonsson, C.W. Tornøe, H. Madsen, Non-linear mixed-effects models with stochastic differential equations: implementation of an estimation algorithm, J. Pharmacokinet. Pharmacodyn. 32 (February(1)) (2005) 85-107; U. Picchini, S. Ditlevsen, A. De Gaetano, Maximum likelihood estimation of a time-inhomogeneous stochastic differential model of glucose dynamics, Math. Med. Biol. 25 (June(2)) (2008) 141-155]. PK/PD models are traditionally based ordinary differential equations (ODEs) with an observation link that incorporates noise. This state-space formulation only allows for observation noise and not for system noise. Extending to SDEs allows for a Wiener noise component in the system equations. This additional noise component enables handling of autocorrelated residuals originating from natural variation or systematic model error. Autocorrelated residuals are often partly ignored in PK/PD modelling although violating the hypothesis for many standard statistical tests. This article presents a package for the statistical program R that is able to handle SDEs in a mixed-effects setting. The estimation method implemented is the FOCE(1) approximation to the population likelihood which is generated from the individual likelihoods that are approximated using the Extended Kalman Filter's one-step predictions.

Differential genetic susceptibility to child risk at birth in predicting observed maternal behavior.

PubMed

Fortuna, Keren; van Ijzendoorn, Marinus H; Mankuta, David; Kaitz, Marsha; Avinun, Reut; Ebstein, Richard P; Knafo, Ariel

2011-01-01

This study examined parenting as a function of child medical risks at birth and parental genotype (dopamine D4 receptor; DRD4). Our hypothesis was that the relation between child risks and later maternal sensitivity would depend on the presence/absence of a genetic variant in the mothers, thus revealing a gene by environment interaction (GXE). Risk at birth was defined by combining risk indices of children's gestational age at birth, birth weight, and admission to the neonatal intensive care unit. The DRD4-III 7-repeat allele was chosen as a relevant genotype as it was recently shown to moderate the effect of environmental stress on parental sensitivity. Mothers of 104 twin pairs provided DNA samples and were observed with their children in a laboratory play session when the children were 3.5 years old. Results indicate that higher levels of risk at birth were associated with less sensitive parenting only among mothers carrying the 7-repeat allele, but not among mothers carrying shorter alleles. Moreover, mothers who are carriers of the 7-repeat allele and whose children scored low on the risk index were observed to have the highest levels of sensitivity. These findings provide evidence for the interactive effects of genes and environment (in this study, children born at higher risk) on parenting, and are consistent with a genetic differential susceptibility model of parenting by demonstrating that some parents are inherently more susceptible to environmental influences, both good and bad, than are others.

Effects of methyl testosterone exposure on sexual differentiation in medaka, Oryzias latipes

USGS Publications Warehouse

Papoulias, D.M.; Noltie, Douglas B.; Tillitt, D.E.

2000-01-01

Studies were conducted to characterize effects of a known androgen on sexual differentiation and development of medaka, Oryzias latipes (d-rR strain), at two life stages. Embryos were injected with graded doses of methyl testosterone (MT) prior to epiboly. The occurrence of sex-reversal, and the gonadosomatic index (GSI) were evaluated in adults. Primary germ cells were counted and gonad volumes calculated for larvae to determine if sex-reversal could be detected at an early life stage. Sex-reversal of genetic females to phenotypic males was observed at both life stages. The GSI for phenotypic females was greater than for phenotypic males, while the GSI in XX males was similar to XY males. MT appeared to reduce the GSI of XX females exposed to MT but not sex-reversed. Our results indicate that embryonic exposure to androgens influences sexual development in medaka. Utilizing the d-rR strain of medaka allows detection of an effect as early as 2 weeks after chemical exposure making this a useful tool to screen chemicals for effects on sexual differentiation. Copyright (C) 2000.

Effects of inorganic lead on the differentiation and growth of cultured hippocampal and neuroblastoma cells.

PubMed

Audesirk, T; Audesirk, G; Ferguson, C; Shugarts, D

1991-01-01

Lead exposure has devastating effects on the developing nervous system, and has been implicated in variety of behavioral and cognitive deficits as well as neural morphological abnormalities. Since lead impacts many calcium-dependent processes, one likely mechanism of lead toxicity is its disruption of calcium dependent processes, among which is neuronal differentiation. We investigated the effects of inorganic lead on survival and several parameters of differentiation of cultured neurons. Three different cell types were used: Rat hippocampal neurons (a primary CNS cell type), B50 rat neuroblastoma cells (a transformed CNS-derived cell line), and N1E-115 mouse neuroblastoma cells (a transformed peripherally-derived cell line). Lead concentrations ranged from low nM to 1 mM. Lead effects differed considerably among the three cell types, with B50 cells least affected. Lead effects were generally multimodal, with fewest effects observed at intermediate concentrations. Lead inhibited neurite initiation in hippocampal neurons, but stimulated initiation in N1E-115 cells. In those cells that differentiated, lead increased dendrite numbers in hippocampal neurons and neurite numbers in N1E-115 cells. Lead exposure increased both the length and the degree of branching of axons in hippocampal neurons and the length of neurites in N1E-115 cells. We hypothesize that lead impacts multiple regulatory processes that influence neuron survival and differentiation, and that its effects show differing dose-dependencies. The differing responses of the different cell types to lead suggests that differentiation may be regulated in different ways by the three types of cells. Alternatively, or additionally, the cell types may differ in their ability to compensate for, sequester, or expel lead.

The effects of differential flow between rational surfaces on toroidal resistive MHD modes

NASA Astrophysics Data System (ADS)

Brennan, Dylan; Halfmoon, Michael; Rhodes, Dov; Cole, Andrew; Okabayashi, Michio; Paz-Soldan, Carlos; Finn, John

2016-10-01

Differential flow between resonant surfaces can strongly affect the coupling and penetration of resonant components of resistive modes, and yet this mechanism is not yet fully understood. This study focuses on the evolution of tearing instabilities and the penetration of imposed resonant magnetic perturbations (RMPs) in tokamak configurations relevant to DIII-D and ITER, including equilibrium flow shear. It has been observed on DIII-D that the onset of tearing instabilities leading to disruption is often coincident with a loss of differential rotation between a higher m/n tearing surface (normally the 4/3 or 3/2) and a lower m/n tearing surface (normally the 2/1). Imposing RMPs can strongly affect this coupling and the torques between the modes. We apply the nonlinear 3-D resistive magnetohydrodynamic (MHD) code NIMROD to study the mechanisms by which these couplings occur. Reduced MHD analyses are applied to study the effects of differential flow between resonant surfaces in the simulations. Interaction between resonant modes can cause significant energy transfer between them, effectively stabilizing one mode while the other grows. The flow mitigates this transfer, but also affects the individual modes. The combination of these effects determines the nonlinear outcome. Supported by US DOE Grants DE-SC0014005 and DE-SC0014119.

The effect of dimethyl sulfoxide on hepatic differentiation of mesenchymal stem cells.

PubMed

Alizadeh, Effat; Zarghami, Nosratollah; Eslaminejad, Mohamadreza Baghaban; Akbarzadeh, Abolfazl; Barzegar, Abolfazl; Mohammadi, Seyed Abolghasem

2016-01-01

Adipose tissue-derived mesenchymal stem cells (AT-MSCs) are suitable choices in autologous stem cell treatment of liver-associated diseases due to their hepatic differentiation potential. Dimethyl sulfoxide (DMSO) is an amphipathic molecule with potential of delivering both lipophilic and hydrophilic agents into cells, also a common cryoprotectant for freezing of the cells. DMSO was used in some protocols for induction of AT-MSCs towards hepatocyte like cells. However, the effect of DMSO on hepatogenic differentiation of AT-MSCs were not surveyed, previously. In the present study, we aimed at evaluation of the effect of DMSO on differentiation of AT-MSCs into hepatic lineage. We isolated mesenchymal stem cells (MSCs) from adipose tissue, and then verifies multi-potency and surface markers of AT-MSCs . Isolated AT-MSCs randomly dispensed in four groups including Group 1: HGF treated, 2: HGF+ DMSO treated, 3: HGF+ DMSO+ OSM treated, and group control for a period of 3 weeks in the expansion medium without serum; EGF and bFGF were also included in the first days of inductions. The morphologic changes during induction period was observed with microscopy. The secretion of albumin (ALB) of the differentiating MSCs was investigated using ELISA, and urea production was evaluated using colorimetric assay. The qRT-PCR was performed for quantitation of hepatocyte marker genes including AFP, ALB, CK18, HNF4a, and HNF6. The glycogen storage of differentiated cells was visualized by periodic-acid Schiff‘s staining. The results demonstrate that DMSO speeds up hepatic differentiation of AT-MSCs characterized by rapid changes in morphology; higher expression of hepatic marker gene (ALB) in both mRNA and protein level (P < 0.05); also increased transcriptional levels of other liver genes including CK18, HNF4a, and HNF6 (P < 0.01); and moreover, greater percentage of glycogen storage(p < 0.05) in DMSO-treated groups. DMSO catalyzes hepatic

Ferroelectric Field-Effect Transistor Differential Amplifier Circuit Analysis

NASA Technical Reports Server (NTRS)

Phillips, Thomas A.; MacLeod, Todd C.; Ho, Fat D.

2008-01-01

There has been considerable research investigating the Ferroelectric Field-Effect Transistor (FeFET) in memory circuits. However, very little research has been performed in applying the FeFET to analog circuits. This paper investigates the use of FeFETs in a common analog circuit, the differential amplifier. The two input Metal-Oxide-Semiconductor (MOS) transistors in a general MOS differential amplifier circuit are replaced with FeFETs. Resistors are used in place of the other three MOS transistors. The FeFET model used in the analysis has been previously reported and was based on experimental device data. Because of the FeFET hysteresis, the FeFET differential amplifier has four different operating modes depending on whether the FeFETs are positively or negatively polarized. The FeFET differential amplifier operation in the different modes was analyzed by calculating the amplifier voltage transfer and gain characteristics shown in figures 2 through 5. Comparisons were made between the FeFET differential amplifier and the standard MOS differential amplifier. Possible applications and benefits of the FeFET differential amplifier are discussed.

Evaluating Differential Effects Using Regression Interactions and Regression Mixture Models

ERIC Educational Resources Information Center

Van Horn, M. Lee; Jaki, Thomas; Masyn, Katherine; Howe, George; Feaster, Daniel J.; Lamont, Andrea E.; George, Melissa R. W.; Kim, Minjung

2015-01-01

Research increasingly emphasizes understanding differential effects. This article focuses on understanding regression mixture models, which are relatively new statistical methods for assessing differential effects by comparing results to using an interactive term in linear regression. The research questions which each model answers, their…

An Effect Size Measure for Raju's Differential Functioning for Items and Tests

ERIC Educational Resources Information Center

Wright, Keith D.; Oshima, T. C.

2015-01-01

This study established an effect size measure for differential functioning for items and tests' noncompensatory differential item functioning (NCDIF). The Mantel-Haenszel parameter served as the benchmark for developing NCDIF's effect size measure for reporting moderate and large differential item functioning in test items. The effect size of…

Differential effect of silybin on the Fe2+-ADP and t-butyl hydroperoxide-induced microsomal lipid peroxidation.

PubMed

Valenzuela, A; Guerra, R

1986-02-15

We have observed a differential effect of silybin dihemisuccinate on rat liver microsomal oxygen consumption and on lipid peroxidation induced by NADPH-Fe2+-ADP and t-butyl hydroperoxide. These results are ascribed to the antioxidant properties of the flavonoid. The differences observed in the effect of the catalysts may be a consequence of the different capacity of silybin to act as a scavenger of free radicals formed by NADPH-Fe2+-ADP or t-butyl hydroperoxide.

The tilt effect in DOAS observations

NASA Astrophysics Data System (ADS)

Lampel, Johannes; Wang, Yang; Hilboll, Andreas; Beirle, Steffen; Sihler, Holger; Puķīte, Janis; Platt, Ulrich; Wagner, Thomas

2017-12-01

Experience of differential atmospheric absorption spectroscopy (DOAS) shows that a spectral shift between measurement spectra and reference spectra is frequently required in order to achieve optimal fit results, while the straightforward calculation of the optical density proves inferior. The shift is often attributed to temporal instabilities of the instrument but implicitly solved the problem of the tilt effect discussed/explained in this paper. Spectral positions of Fraunhofer and molecular absorption lines are systematically shifted for different measurement geometries due to an overall slope - or tilt - of the intensity spectrum. The phenomenon has become known as the tilt effect for limb satellite observations, where it is corrected for in a first-order approximation, whereas the remaining community is less aware of its cause and consequences. It is caused by the measurement process, because atmospheric absorption and convolution in the spectrometer do not commute. Highly resolved spectral structures in the spectrum will first be modified by absorption and scattering processes in the atmosphere before they are recorded with a spectrometer, which convolves them with a specific instrument function. In the DOAS spectral evaluation process, however, the polynomial (or other function used for this purpose) accounting for broadband absorption is applied after the convolution is performed. In this paper, we derive that changing the order of the two modifications of the spectra leads to different results. Assuming typical geometries for the observations of scattered sunlight and a spectral resolution of 0.6 nm, this effect can be interpreted as a spectral shift of up to 1.5 pm, which is confirmed in the actual analysis of the ground-based measurements of scattered sunlight as well as in numerical radiative transfer simulations. If no spectral shift is allowed by the fitting routine, residual structures of up to 2.5 × 10-3 peak-to-peak are observed. Thus, this effect

The differential effect of basic fibroblast growth factor and stromal cell‑derived factor‑1 pretreatment on bone morrow mesenchymal stem cells osteogenic differentiation potency.

PubMed

Wang, Ruolin; Liu, Wenhua; Du, Mi; Yang, Chengzhe; Li, Xuefen; Yang, Pishan

2018-03-01

In situ tissue engineering has become a novel strategy to repair periodontal/bone tissue defects. The choice of cytokines that promote the recruitment and proliferation, and potentiate and maintain the osteogenic differentiation ability of mesenchymal stem cells (MSCs) is the key point in this technique. Stromal cell‑derived factor‑1 (SDF‑1) and basic fibroblast growth factor (bFGF) have the ability to promote the recruitment, and proliferation of MSCs; however, the differential effect of SDF‑1 and bFGF pretreatment on MSC osteogenic differentiation potency remains to be explored. The present study comparatively observed osteogenic differentiation of bone morrow MSCs (BMMSCs) pretreated by bFGF or SDF‑1 in vitro. The gene and protein expression levels of alkaline phosphatase (ALP), runt related transcription factor 2 (Runx‑2) and bone sialoprotein (BSP) were detected using reverse transcription‑quantitative polymerase chain reaction and western blotting. The results showed that the expression of ALP mRNA on day 3, and BSP and Runx‑2 mRNA on day 7 in the bFGF pretreatment group was significantly higher than those in SDF‑1 pretreatment group. Expression levels of Runx‑2 mRNA, and ALP and Runx‑2 protein on day 3 in the SDF‑1 pretreatment group were higher than those in the bFGF pretreatment group. However, there was no significant difference in osteogenic differentiation ability on day 14 and 28 between the bFGF‑ or SDF‑1‑pretreatment groups and the control. In conclusion, bFGF and SDF‑1 pretreatment inhibits osteogenic differentiation of BMMSCs at the early stage, promotes it in the medium phase, and maintains it in the later stage during osteogenic induction, particularly at the mRNA level. Out of the two cytokines, bFGF appeared to have a greater effect on osteogenic differentiation.

Are two hands (from different people) better than one? Mode effects and differential transfer between manual coordination modes.

PubMed

Gorman, Jamie C; Crites, Michael J

2013-08-01

We report an experiment in which we investigated differential transfer between unimanual (one-handed), bimanual (two-handed), and intermanual (different peoples' hands) coordination modes. People perform some manual tasks faster than others ("mode effects"). However, little is known about transfer between coordination modes. To investigate differential transfer, we draw hypotheses from two perspectives--information based and constraint based--of bimanual and interpersonal coordination and skill acquisition. Participants drove a teleoperated rover around a circular path in sets of two 2-min trials using two of the different coordination modes. Speed and variability of the rover's path were measured. Order of coordination modes was manipulated to examine differential transfer and mode effects. Differential transfer analyses revealed patterns of positive transfer from simpler (localized spatiotemporal constraints) to more complex (distributed spatiotemporal constraints) coordination modes paired with negative transfer in the opposite direction. Mode effects indicated that intermanual performance was significantly faster than unimanual performance, and bimanual performance was intermediate. Importantly, all of these effects disappeared with practice. The observed patterns of differential transfer between coordination modes may be better accounted for by a constraint-based explanation of differential transfer than by an information-based one. Mode effects may be attributable to anticipatory movements based on dyads' access to mutual visual information. Although people may be faster using more-complex coordination modes, when operators transition between modes, they may be more effective transitioning from simpler (e.g., bimanual) to more complex (e.g., intermanual) modes than vice versa. However, this difference may be critical only for novel or rarely practiced tasks.

Stage-specific effects of FGF2 on the differentiation of dental pulp cells

PubMed Central

Sagomonyants, Karen; Mina, Mina

2015-01-01

Dentinogenesis is a complex and multistep process, which is regulated by various growth factors, including members of the Fibroblast Growth Factor (FGF) family. Both positive and negative effects of FGFs on dentinogenesis have been reported but the underlying mechanisms of these conflicting results are still unclear. To gain better insight into the role of FGF2 in dentinogenesis, we used dental pulp cells from various transgenic mice, in which fluorescent protein expression identifies cells at different stages of odontoblast differentiation. Our results showed that continuous exposure of pulp cells to FGF2 inhibited mineralization and revealed both stimulatory and inhibitory effects of FGF2 on expression of markers of dentinogenesis and various transgenes. During the proliferation phase of in vitro growth FGF2 increased expression of markers of dentinogenesis and the percentages of DMP1-GFP+ functional odontoblasts and DSPP-Cerulean+ odontoblasts. Additional exposure to FGF2 during the differentiation/mineralization phase of in vitro growth decreased the extent of mineralization, expression of markers of dentinogenesis, and expression of DMP1-GFP and DSPP-Cerulean transgenes. Recovery experiments showed that the inhibitory effects of FGF2 on dentinogenesis were related to the blocking of differentiation of cells into mature odontoblasts. These observations together showed stage-specific effects of FGF2 on dentinogenesis by dental pulp cells and provide critical information for the development of improved treatments for vital pulp therapy and dentin regeneration. PMID:25823776

Anti-stress and neuronal cell differentiation induction effects of Rosmarinus officinalis L. essential oil.

PubMed

Villareal, Myra O; Ikeya, Ayumi; Sasaki, Kazunori; Arfa, Abdelkarim Ben; Neffati, Mohamed; Isoda, Hiroko

2017-12-22

Mood disorder accounts for 13 % of global disease burden. And while therapeutic agents are available, usually orally administered, most have unwanted side effects, and thus making the inhalation of essential oils (EOs) an attractive alternative therapy. Rosmarinus officinalis EO (ROEO), Mediterranean ROEO reported to improve cognition, mood, and memory, the effect on stress of which has not yet been determined. Here, the anti-stress effect of ROEO on stress was evaluated in vivo and in vitro. Six-week-old male ICR mice were made to inhale ROEO and subjected to tail suspension test (TST). To determine the neuronal differentiation effect of ROEO in vitro, induction of ROEO-treated PC12 cells differentiation was observed. Intracellular acetylcholine and choline, as well as the Gap43 gene expression levels were also determined. Inhalation of ROEO significantly decreased the immobility time of ICR mice and serum corticosterone level, accompanied by increased brain dopamine level. Determination of the underlying mechanism in vitro revealed a PC12 differentiation-induction effect through the modulation of intracellular acetylcholine, choline, and Gap43 gene expression levels. ROEO activates the stress response system through the NGF pathway and the hypothalamus-pituitary-adrenal axis, promoting dopamine production and secretion. The effect of ROEO may be attributed to its bioactive components, specifically to α-pinene, one of its major compounds that has anxiolytic property. The results of this study suggest that ROEO inhalation has therapeutic potential against stress-related psychiatric disorders.

Quantifying the effect of riming on snowfall using ground-based observations

NASA Astrophysics Data System (ADS)

Moisseev, Dmitri; von Lerber, Annakaisa; Tiira, Jussi

2017-04-01

Ground-based observations of ice particle size distribution and ensemble mean density are used to quantify the effect of riming on snowfall. The rime mass fraction is derived from these measurements by following the approach that is used in a single ice-phase category microphysical scheme proposed for the use in numerical weather prediction models. One of the characteristics of the proposed scheme is that the prefactor of a power law relation that links mass and size of ice particles is determined by the rime mass fraction, while the exponent does not change. To derive the rime mass fraction, a mass-dimensional relation representative of unrimed snow is also determined. To check the validity of the proposed retrieval method, the derived rime mass fraction is converted to the effective liquid water path that is compared to microwave radiometer observations. Since dual-polarization radar observations are often used to detect riming, the impact of riming on dual-polarization radar variables is studied for differential reflectivity measurements. It is shown that the relation between rime mass fraction and differential reflectivity is ambiguous, other factors such as change in median volume diameter need also be considered. Given the current interest on sensitivity of precipitation to aerosol pollution, which could inhibit riming, the importance of riming for surface snow accumulation is investigated. It is found that riming is responsible for 5% to 40% of snowfall mass. The study is based on data collected at the University of Helsinki field station in Hyytiälä during U.S. Department of Energy Biogenic Aerosols Effects on Clouds and Climate (BAECC) field campaign and the winter 2014/2015. In total 22 winter storms were analyzed, and detailed analysis of two events is presented to illustrate the study.

Effect of heat flux on differential rotation in turbulent convection.

PubMed

Kleeorin, Nathan; Rogachevskii, Igor

2006-04-01

We studied the effect of the turbulent heat flux on the Reynolds stresses in a rotating turbulent convection. To this end we solved a coupled system of dynamical equations which includes the equations for the Reynolds stresses, the entropy fluctuations, and the turbulent heat flux. We used a spectral tau approximation in order to close the system of dynamical equations. We found that the ratio of the contributions to the Reynolds stresses caused by the turbulent heat flux and the anisotropic eddy viscosity is of the order of approximately 10(L rho/l0)2, where l0 is the maximum scale of turbulent motions and L rho is the fluid density variation scale. This effect is crucial for the formation of the differential rotation and should be taken into account in the theories of the differential rotation of the Sun, stars, and planets. In particular, we demonstrated that this effect may cause the differential rotation which is comparable with the typical solar differential rotation.

Differential shift in spatial bias over time depends on observers׳ initial bias: Observer subtypes, or regression to the mean?

PubMed

Newman, Daniel P; Loughnane, Gerard M; Abe, Rafael; Zoratti, Marco T R; Martins, Ana C P; van den Bogert, Petra C; Kelly, Simon P; O'Connell, Redmond G; Bellgrove, Mark A

2014-11-01

Healthy subjects typically exhibit a subtle bias of visuospatial attention favouring left space that is commonly termed 'pseudoneglect'. This bias is attenuated, or shifted rightwards, with decreasing alertness over time, consistent with theoretical models proposing that pseudoneglect is a result of the right hemisphere׳s dominance in regulating attention. Although this 'time-on-task effect' for spatial bias is observed when averaging across whole samples of healthy participants, Benwell, C. S. Y., Thut, G., Learmonth, G., & Harvey, M. (2013b). Spatial attention: differential shifts in pseudoneglect direction with time-on-task and initial bias support the idea of observer subtypes. Neuropsychologia, 51(13), 2747-2756 recently presented evidence that the direction and magnitude of bias exhibited by the participant early in the task (left biased, no bias, or right biased) were stable traits that predicted the direction of the subsequent time-on-task shift in spatial bias. That is, the spatial bias of participants who were initially left biased shifted in a rightward direction with time, whereas that of participants who were initially right biased shifted in a leftward direction. If valid, the data of Benwell et al. are potentially important and may demand a re-evaluation of current models of the neural networks governing spatial attention. Here we use two novel spatial attention tasks in an attempt to confirm the results of Benwell et al. We show that rather than being indicative of true participant subtypes, these data patterns are likely driven, at least in part, by 'regression towards the mean' arising from the analysis method employed. Although evidence supports the contention that trait-like individual differences in spatial bias exist within the healthy population, no clear evidence is yet available for participant/observer subtypes in the direction of time-on-task shift in spatial biases. Copyright © 2014 Elsevier Ltd. All rights reserved.

Gunn-Hilsum Effect in Mechanically Strained Silicon Nanowires: Tunable Negative Differential Resistance.

PubMed

Shiri, Daryoush; Verma, Amit; Nekovei, Reza; Isacsson, Andreas; Selvakumar, C R; Anantram, M P

2018-04-19

Gunn (or Gunn-Hilsum) Effect and its associated negative differential resistivity (NDR) emanates from transfer of electrons between two different energy subbands. This effect was observed in semiconductors like GaAs which has a direct bandgap of very low effective mass and an indirect subband of high effective mass which lies ~300 meV above the former. In contrast to GaAs, bulk silicon has a very high energy spacing (~1 eV) which renders the initiation of transfer-induced NDR unobservable. Using Density Functional Theory (DFT), semi-empirical 10 orbital (sp 3 d 5 s * ) Tight Binding and Ensemble Monte Carlo (EMC) methods we show for the first time that (a) Gunn Effect can be induced in silicon nanowires (SiNW) with diameters of 3.1 nm under +3% strain and an electric field of 5000 V/cm, (b) the onset of NDR in the I-V characteristics is reversibly adjustable by strain and (c) strain modulates the resistivity by a factor 2.3 for SiNWs of normal I-V characteristics i.e. those without NDR. These observations are promising for applications of SiNWs in electromechanical sensors and adjustable microwave oscillators. It is noteworthy that the observed NDC is different in principle from Esaki-Diode and Resonant Tunneling Diodes (RTD) in which NDR originates from tunneling effect.

Effect of ECM2 expression on bovine skeletal muscle-derived satellite cell differentiation.

PubMed

Liu, Chang; Tong, Huili; Li, Shufeng; Yan, Yunqin

2018-05-01

Extracellular matrix components have important regulatory functions during cell proliferation and differentiation. In recent study, extracellular matrix were shown to have a strong effect on skeletal muscle differentiation. Here, we aimed to elucidate the effects of extracellular matrix protein 2 (ECM2), an extracellular matrix component, on the differentiation of bovine skeletal muscle-derived satellite cells (MDSCs). Western blot and immunofluorescence analyses were used to elucidate the ECM2 expression pattern in bovine MDSCs during differentiation in vitro. CRISPR/Cas9 technology was used to activate or inhibit ECM2 expression to study its effects on the in vitro differentiation of bovine MDSCs. ECM2 expression was shown to increase gradually during bovine MDSC differentiation, and the levels of this protein were higher in more highly differentiated myotubes. ECM2 activation promoted MDSC differentiation, whereas its suppression inhibited the differentiation of these cells. Here, for the first time, we demonstrated the importance of ECM2 expression during bovine MDSC differentiation; these results could lead to treatments that help to increase beef cattle muscularity. © 2018 International Federation for Cell Biology.

The effect of bisphosphonates on the endothelial differentiation of mesenchymal stem cells

PubMed Central

Sharma, Dileep; Hamlet, Stephen Mark; Petcu, Eugen Bogdan; Ivanovski, Saso

2016-01-01

The contribution of the local stem cell niche to providing an adequate vascular framework during healing cannot be overemphasized. Bisphosphonates (BPs) are known to have a direct effect on the local vasculature, but their effect on progenitor cell differentiation is unknown. This in vitro study evaluated the effect(s) of various BPs on the differentiation of human placental mesenchymal stem cells (pMSCs) along the endothelial lineage and their subsequent functional and morphogenic capabilities. pMSC multipotency was confirmed by successful differentiation into cells of both the osteogenic and endothelial lineages, as demonstrated by positive Alizarin Red S staining and Ac-LDL uptake. pMSC differentiation in the presence of non-cytotoxic BP concentrations showed that nitrogen containing BPs had a significant inhibitory effect on cell migration and endothelial marker gene expression, as well as compromised endothelial differentiation as demonstrated using von Willebrand factor immunofluorescence staining and tube formation assay. This in vitro study demonstrated that at non-cytotoxic levels, nitrogen-containing BPs inhibit differentiation of pMSCs into cells of an endothelial lineage and affect the downstream functional capability of these cells supporting a multi-modal effect of BPs on angiogenesis as pathogenic mechanism contributing to bone healing disorders such as bisphosphonate related osteonecrosis of the jaws (BRONJ). PMID:26857282

Differential Effects of Science Study Questions.

ERIC Educational Resources Information Center

Holliday, William G.; And Others

The purpose of this study was to investigate the differential effects on low and high verbal students of verbatim study questions adjunct to a text describing science concepts. The sample consisted of 217 eighth grade students enrolled in twelve Calgary (Alberta, Canada) schools. Materials developed for the study included an introduction to the…

Positivity effect in healthy aging in observational but not active feedback-learning.

PubMed

Bellebaum, Christian; Rustemeier, Martina; Daum, Irene

2012-01-01

The present study investigated the impact of healthy aging on the bias to learn from positive or negative performance feedback in observational and active feedback learning. In active learning, a previous study had already shown a negative learning bias in healthy seniors older than 75 years, while no bias was found for younger seniors. However, healthy aging is accompanied by a 'positivity effect', a tendency to primarily attend to stimuli with positive valence. Based on recent findings of dissociable neural mechanisms in active and observational feedback learning, the positivity effect was hypothesized to influence older participants' observational feedback learning in particular. In two separate experiments, groups of young (mean age 27) and older participants (mean age 60 years) completed an observational or active learning task designed to differentially assess positive and negative learning. Older but not younger observational learners showed a significant bias to learn better from positive than negative feedback. In accordance with previous findings, no bias was found for active learning. This pattern of results is discussed in terms of differences in the neural underpinnings of active and observational learning from performance feedback.

Effects of Cinnamoyloxy-mammeisin from Geopropolis on Osteoclast Differentiation and Porphyromonas gingivalis-Induced Periodontitis.

PubMed

da Cunha, Marcos Guilherme; Ramos-Junior, Erivan Schnaider; Franchin, Marcelo; Taira, Thaise Mayumi; Beutler, John A; Franco, Gilson Cesar Nobre; Ikegaki, Masaharu; de Alencar, Severino Matias; Fukada, Sandra Yasuyo; Rosalen, Pedro Luiz

2017-06-23

Bone-loss-related diseases such as rheumatoid arthritis, osteomyelitis, osteoporosis, and periodontitis are associated with high rates of morbidity worldwide. These disorders are characterized by an imbalance between the formation and activity of osteoblasts and osteoclasts, leading to bone loss. In this context, we evaluated the effect of cinnamoyloxy-mammeisin (CNM), an anti-inflammatory coumarin found in Melipona scutellaris geopropolis, on key targets related to bone remodeling. In the present study we investigated the in vitro effects of CNM on osteoclast differentiation and M-CSF+RANKL-induced osteoclastogenic marker expression. Additionally, the interference of CNM treatment on osteoclast activity was evaluated by zymography and resorption area. Finally, we assessed the capacity of the compound to mitigate alveolar bone loss in vivo in experimental murine periodontitis induced by Porphyromonas gingivalis. We observed that treatment with CNM impaired osteoclast differentiation, as evidenced by a reduced number of tartrate-resistant acid-phosphatase-positive multinucleated cells (TRAP+) as well as the expression of osteoclastogenic markers upon M-CSF+RANKL-induced stimulation. Similarly, we observed reduced gelatinolytic and resorption capacity in M-CSF+RANKL-induced cells in vitro. Lastly, CNM attenuated alveolar bone loss in an experimental murine periodontitis model. These findings indicate that CNM may be considered a promising treatment for bone loss diseases.

Synergetic effect of topological cue and periodic mechanical tension-stress on osteogenic differentiation of rat bone mesenchymal stem cells.

PubMed

Liu, Yao; Yang, Guang; Ji, Huanzhong; Xiang, Tao; Luo, En; Zhou, Shaobing

2017-06-01

Mesenchymal stem cells (MSCs) are able to self-renew and differentiate into tissues of mesenchymal origin, making them to be significant for cell-based therapies, such as metabolic bone diseases and bone repair. Regulating the differentiation of MSCs is significant for bone regeneration. Electrospun fibers mimicking natural extracellular matrix (ECM), is an effective artificial ECM to regulate the behaviors and fates of MSCs. The aligned electrospun fibers can modulate polar cell pattern of bone mesenchymal stem cells, which leads to more obvious osteogenic differentiation. Apart from the topographic effect of electrospun fibers, mechanical cues can also intervene the cell behaviors. In this study, the osteogenic differentiation of rat bone mesenchymal stem cells was evaluated, which were cultured on aligned/random electrospun fiber mats materials under mechanical tension intervention. Scanning electron microscope and immune-fluorescent staining were used to directly observe the polarity changing of cellular morphology and cytoskeleton. The results proved that aligned electrospun fibers could be more conducive to promote osteogenic differentiation of rat bone mesenchymal stem cells and this promotion of osteogenic differentiation was enhanced by tension intervention. These results were correlated to the quantitative real-time PCR assay. In general, culturing rat bone mesenchymal stem cells on electrospun fibers under the intervention of mechanical tension is an effective way to mimic a more real cellular microenvironment. Copyright © 2017 Elsevier B.V. All rights reserved.

Observation of two-center interference effects for electron impact ionization of N2

NASA Astrophysics Data System (ADS)

Chaluvadi, Hari; Nur Ozer, Zehra; Dogan, Mevlut; Ning, Chuangang; Colgan, James; Madison, Don

2015-08-01

In 1966, Cohen and Fano (1966 Phys. Rev. 150 30) suggested that one should be able to observe the equivalent of Young’s double slit interference if the double slits were replaced by a diatomic molecule. This suggestion inspired many experimental and theoretical studies searching for double slit interference effects both for photon and particle ionization of diatomic molecules. These effects turned out to be so small for particle ionization that this work proceeded slowly and evidence for interference effects were only found by looking at cross section ratios. Most of the early particle work concentrated on double differential cross sections for heavy particle scattering and the first evidence for two-center interference for electron-impact triple differential cross section (TDCS) did not appear until 2006 for ionization of H2. Subsequent work has now firmly established that two-center interference effects can be seen in the TDCS for electron-impact ionization of H2. However, in spite of several experimental and theoretical studies, similar effects have not been found for electron-impact ionization of N2. Here we report the first evidence for two-center interference for electron-impact ionization of N2.

Enamel Matrix Derivative has No Effect on the Chondrogenic Differentiation of Mesenchymal Stem Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Groeneveldt, Lisanne C.; Knuth, Callie; Witte-Bouma, Janneke

2014-09-02

Background: Treatment of large bone defects due to trauma, tumor resection, or congenital abnormalities is challenging. Bone tissue engineering using mesenchymal stem cells (MSCs) represents a promising treatment option. However, the quantity and quality of engineered bone tissue are not sufficient to fill large bone defects. The aim of this study was to determine if the addition of enamel matrix derivative (EMD) improves in vitro chondrogenic priming of MSCs to ultimately improve in vivo MSC mediated endochondral bone formation. Methods: MSCs were chondrogenically differentiated in 2.0 × 10{sup 5} cell pellets in medium supplemented with TGFβ3 in the absence ormore » presence of 1, 10, or 100 μg/mL EMD. Samples were analyzed for gene expression of RUNX2, Col II, Col X, and Sox9. Protein and glycoaminoglycan (GAG) production were also investigated via DMB assays, histology, and immunohistochemistry. Osteogenic and adipogenic differentiation capacity were also assessed. Results: The addition of EMD did not negatively affect chondrogenic differentiation of adult human MSCs. EMD did not appear to alter GAG production or expression of chondrogenic genes. Osteogenic and adipogenic differentiation were also unaffected though a trend toward decreased adipogenic gene expression was observed. Conclusion: EMD does not affect chondrogenic differentiation of adult human MSCs. As such the use of EMD in combination with chondrogenically primed MSCs for periodontal bone tissue repair is unlikely to have negative effects on MSC differentiation.« less

PRELIMINARY OBSERVATIONS OF ATRAZINE-INDUCED EFFECTS UPON GONADAL DIFFERENTIATION IN RIVULUS MARMORATUS, A NATURALLY HERMAPHRODITIC FISH

EPA Science Inventory

The commonly used agricultural herbicide atrazine has been recognized as an endocrine disrupting chemical. In amphibians and reptiles, atrazine has been reported to alter sexual differentiation and induce secondary sexual characteristics that have been attributed to enhanced arom...

Differential pricing of drugs: a role for cost-effectiveness analysis?

PubMed

Lopert, Ruth; Lang, Danielle L; Hill, Suzanne R; Henry, David A

2002-06-15

Internationally, the high costs of pharmaceutical products limit access to treatment. The principle of differential pricing is that drug prices should vary according to some measure of affordability. How differential prices should be determined is, however, unclear. Here we describe a method whereby differential prices for essential drugs could be derived in countries of variable national wealth, and, using angiotensin-converting enzyme inhibitors provide an example of how the process might work. Indicative prices for drugs can be derived by cost-effectiveness analysis that incorporates a measure of national wealth. Such prices could be used internationally as a basis of differential price negotiations.

The Effect of Spaceflight on Cartilage Cell Cycle and Differentiation

NASA Technical Reports Server (NTRS)

Doty, Stephen B.; Stiner, Dalina; Telford, William G.

2000-01-01

In vivo studies have shown that spaceflight results in loss of bone and muscle. In an effort to understand the mechanisms of these changes, cell cultures of cartilage, bone and muscle have been subjected to spaceflight to study the microgravity effects on differentiated cells. However it now seems possible that the cell differentiation process itself may be the event(s) most affected by spaceflight. For example, osteoblast-like cells have been shown to have reduced cellular activity in microgravity due to an underdifferentiated state (Carmeliet, et al, 1997). And reduced human lymphocyte growth in spaceflight was related to increased apoptosis (Lewis, et al, 1998). Which brings us to the question of whether reduced cellular activity in space is due to an effect on the differentiated cell, an effect on the cell cycle and cell proliferation, or an effect on cell death. This question has not been specifically addressed on previous flights and was the question behind die present study.

[Clinical application of moving cupping therapy based on skin reaction observation and syndrome differentiation].

PubMed

Deng, Xiao-Lan; Chen, Bo; Chen, Ze-Lin

2014-12-01

The diagnostic evidence on clinical diseases and theoretic basis of moving cupping therapy were ex- plored in the paper. By the observation of the local reaction, such as skin appearance and color, the affected location, duration of sickness and nature of disease were judged. Different moving cupping methods were selected for different disorders. It was discovered that the property of syndromes should be recognized by the palpation on skin and muscle in the moving cupping therapy so that the pathogenesis and treating principle could be carefully determined. The moving cupping therapy is the important component of body surface therapy. Skin reaction observation and syndrome differentiation is the essential guidance of the moving cupping therapy.

Effect of Differential Item Functioning on Test Equating

ERIC Educational Resources Information Center

Kabasakal, Kübra Atalay; Kelecioglu, Hülya

2015-01-01

This study examines the effect of differential item functioning (DIF) items on test equating through multilevel item response models (MIRMs) and traditional IRMs. The performances of three different equating models were investigated under 24 different simulation conditions, and the variables whose effects were examined included sample size, test…

Differential biological effects of dehydroepiandrosterone (DHEA) between mouse (B16F10) and human melanoma (BLM) cell lines.

PubMed

Joshi, Kumud; Hassan, Sherif S; Ramaraj, Pandurangan

2017-01-01

Dehydroepiandrosterone (DHEA) is a weak androgen and had been shown to have anti-cancer, anti-adipogenic and anti-inflammatory effects on mouse and other rodent models, but not on humans, suggesting a systemic level difference between mouse and human. Our previous study on DHEA biological functions involving a variety of cell lines, suggested that the functional differences between mouse and human existed even at the cellular level. Hence, using mouse and human melanoma cell models, in-vitro effects of DHEA on cell growth, mechanism of cell death and mechanism of DHEA action were studied. Results indicated a differential biological effects of DHEA between mouse and human melanoma cell lines. These in-vitro studies also suggested that the differential biological effects observed between these two cell lines could be due to the difference in the way DHEA was processed or metabolized inside the cell.

Monitoring subsurface coal fires in Jharia coalfield using observations of land subsidence from differential interferometric synthetic aperture radar (DInSAR)

NASA Astrophysics Data System (ADS)

Gupta, Nishant; Syed, Tajdarul H.; Athiphro, Ashiihrii

2013-10-01

Coal fires in the Jharia coalfield pose a serious threat to India's vital resource of primary coking coal and the regional environment. In order to undertake effective preventative measures, it is critical to detect the occurrence of subsurface coal fires and to monitor the extent of the existing ones. In this study, Differential Interferometric Synthetic Aperature Radar (DInSAR) technique has been utilized to monitor subsurface coal fires in the Jharia coalfield. Results showed that majority of the coal fire-related subsidence were concentrated on the eastern and western boundaries of the coalfield. The magnitude of subsidence observed was classified into high (10-27.8 mm), low (0-10 mm) and upliftment (-10-0 mm). The results were strongly supported by in situ observations and satellite-based thermal imagery analysis. Major subsidence was observed in the areas with repeated sightings of coal fire. Further, the study highlighted on the capability of the methodology for predicting potential coal fire zones on the basis of land surface subsidence only. The results from this study have major implications for demarcating the hazardous coal fire areas as well as effective implementation of public safety measures.

A grounded theory study on the role of differentiated instruction in effective middle school science teaching

NASA Astrophysics Data System (ADS)

Jones, Brian Kirby

The purpose of this grounded theory study was to develop a model explaining the role of differentiated instruction (DI) in effective middle school science teaching. The study examined the best teaching practices and differentiated elements from eight general education middle school science teachers, all scoring at the highest level of a teaching effectiveness measure on their evaluations, through a collection of observational, interview, survey, and teaching artifact data. The data were analyzed through the methodology of a systematic grounded theory qualitative approach using open, axial, and selective coding to develop a model describing how and to what degree effective middle school science teachers differentiated their best teaching practices. The model that emerged from the data shows instruction as a four-phase process and highlights the major elements of best practices and DI represented at each phase. The model also depicts how teachers narrowed the scope of their differentiating strategies as instruction progressed. The participants incorporated DI into their pedagogies, though in different degrees at each phase, and primarily by using variety to present concepts with multiple types of instruction followed by a series of sense-making activities related to several learning modalities. Teachers scaffolded students carefully, using informal and formal assessment data to inform future instructional decisions and especially their plans to reteach or extend on a concept. The model is intended to provide insight into the value of DI for middle school science teaching.

Differential Effects of Antiepileptic Drugs on Neonatal Outcomes

PubMed Central

Pennell, P.B.; Klein, A.M.; Browning, N.; Baker, G.A.; Clayton-Smith, J.; Kalayjian, L.A.; Liporace, J.D.; Privitera, M.; Crawford, T.; Loring, D.W.; Meador, K.J.

2012-01-01

Offspring of women with epilepsy (WWE) on AEDs are at increased risks for major congenital malformations and reduced cognition. They may be at risk for other adverse neonatal outcomes. WWE on carbamazepine (CBZ), lamotrigine (LTG), phenytoin (PHT), or valproate (VPA) monotherapy were enrolled in a prospective, observational, multicenter study of the neurodevelopmental effects of AEDs. The odds ratio for small for gestational age (SGA) was higher for VPA vs. PHT, VPA vs. LTG, and CBZ vs. PHT. Microcephaly rates were elevated to 12% for all newborns and 12-months-old, but normalized by age 24-months. Reduced Apgar scores occurred more frequently in the VPA and PHT groups at 1 minute, but scores were near normal in all groups at 5 minutes. This study demonstrates increased risks for being born SGA in the VPA and CBZ groups, and transiently reduced Apgar scores in the VPA and PHT groups. Differential risks amongst the AEDs can help inform decisions about AED selection for women during childbearing years. PMID:22749607

Robust back-stepping output feedback trajectory tracking for quadrotors via extended state observer and sigmoid tracking differentiator

NASA Astrophysics Data System (ADS)

Shao, Xingling; Liu, Jun; Wang, Honglun

2018-05-01

In this paper, a robust back-stepping output feedback trajectory tracking controller is proposed for quadrotors subject to parametric uncertainties and external disturbances. Based on the hierarchical control principle, the quadrotor dynamics is decomposed into translational and rotational subsystems to facilitate the back-stepping control design. With given model information incorporated into observer design, a high-order extended state observer (ESO) that relies only on position measurements is developed to estimate the remaining unmeasurable states and the lumped disturbances in rotational subsystem simultaneously. To overcome the problem of "explosion of complexity" in the back-stepping design, the sigmoid tracking differentiator (STD) is introduced to compute the derivative of virtual control laws. The advantage is that the proposed controller via output-feedback scheme not only can ensure good tracking performance using very limited information of quadrotors, but also has the ability of handling the undesired uncertainties. The stability analysis is established using the Lyapunov theory. Simulation results demonstrate the effectiveness of the proposed control scheme in achieving a guaranteed tracking performance with respect to an 8-shaped reference trajectory.

Effects of mass variation on structures of differentially rotating polytropic stars

NASA Astrophysics Data System (ADS)

Kumar, Sunil; Saini, Seema; Singh, Kamal Krishan

2018-07-01

A method is proposed for determining equilibrium structures and various physical parameters of differentially rotating polytropic models of stars, taking into account the effect of mass variation inside the star and on its equipotential surfaces. The law of differential rotation has been assumed to be the form of ω2(s) =b1 +b2s2 +b3s4 . The proposed method utilizes the averaging approach of Kippenhahn and Thomas and concepts of Roche-equipotential to incorporate the effects of differential rotation on the equilibrium structures of polytropic stellar models. Mathematical expressions of determining the equipotential surfaces, volume, surface area and other physical parameters are also obtained under the effects of mass variation inside the stars. Some significant conclusions are also drawn.

Effects of Arsenic on Osteoblast Differentiation in Vitro and on Bone Mineral Density and Microstructure in Rats

PubMed Central

Wu, Cheng-Tien; Lu, Tung-Ying; Chan, Ding-Cheng; Tsai, Keh-Sung; Yang, Rong-Sen

2014-01-01

Background: Arsenic is a ubiquitous toxic element and is known to contaminate drinking water in many countries. Several epidemiological studies have shown that arsenic exposure augments the risk of bone disorders. However, the detailed effect and mechanism of inorganic arsenic on osteoblast differentiation of bone marrow stromal cells and bone loss still remain unclear. Objectives: We investigated the effects and mechanism of arsenic on osteoblast differentiation in vitro and evaluated bone mineral density (BMD) and bone microstructure in rats at doses relevant to human exposure from drinking water. Methods: We used a cell model of rat primary bone marrow stromal cells (BMSCs) and a rat model of long-term exposure with arsenic-contaminated drinking water, and determined bone microstructure and BMD in rats by microcomputed tomography (μCT). Results: We observed significant attenuation of osteoblast differentiation after exposure of BMSCs to arsenic trioxide (0.5 or 1 μM). After arsenic treatment during differentiation, expression of runt-related transcription factor-2 (Runx2), bone morphogenetic protein-2 (BMP-2), and osteocalcin in BMSCs was inhibited and phosphorylation of enhanced extracellular signal-regulated kinase (ERK) was increased. These altered differentiation-related molecules could be reversed by the ERK inhibitor PD98059. Exposure of rats to arsenic trioxide (0.05 or 0.5 ppm) in drinking water for 12 weeks altered BMD and microstructure, decreased Runx2 expression, and increased ERK phosphorylation in bones. In BMSCs isolated from arsenic-treated rats, osteoblast differentiation was inhibited. Conclusions: Our results suggest that arsenic is capable of inhibiting osteoblast differentiation of BMSCs via an ERK-dependent signaling pathway and thus increasing bone loss. Citation: Wu CT, Lu TY, Chan DC, Tsai KS, Yang RS, Liu SH. 2014. Effects of arsenic on osteoblast differentiation in vitro and on bone mineral density and microstructure in rats. Environ

Glucocorticoid-induced Leucine Zipper (GILZ) and Long GILZ Inhibit Myogenic Differentiation and Mediate Anti-myogenic Effects of Glucocorticoids*

PubMed Central

Bruscoli, Stefano; Donato, Valerio; Velardi, Enrico; Di Sante, Moises; Migliorati, Graziella; Donato, Rosario; Riccardi, Carlo

2010-01-01

Myogenesis is a process whereby myoblasts differentiate and fuse into multinucleated myotubes, the precursors of myofibers. Various signals and factors modulate this process, and glucocorticoids (GCs) are important regulators of skeletal muscle metabolism. We show that glucocorticoid-induced leucine zipper (GILZ), a GC-induced gene, and the newly identified isoform long GILZ (L-GILZ) are expressed in skeletal muscle tissue and in C2C12 myoblasts where GILZ/L-GILZ maximum expression occurs during the first few days in differentiation medium. Moreover, we observed that GC treatment of myoblasts, which increased GILZ/L-GILZ expression, resulted in reduced myotube formation, whereas GILZ and L-GILZ silencing dampened GC effects. Inhibition of differentiation caused by GILZ/L-GILZ overexpression correlated with inhibition of MyoD function and reduced expression of myogenin. Notably, results indicate that GILZ and L-GILZ bind and regulate MyoD/HDAC1 transcriptional activity, thus mediating the anti-myogenic effect of GCs. PMID:20124407

Mixed Effects Modeling Using Stochastic Differential Equations: Illustrated by Pharmacokinetic Data of Nicotinic Acid in Obese Zucker Rats.

PubMed

Leander, Jacob; Almquist, Joachim; Ahlström, Christine; Gabrielsson, Johan; Jirstrand, Mats

2015-05-01

Inclusion of stochastic differential equations in mixed effects models provides means to quantify and distinguish three sources of variability in data. In addition to the two commonly encountered sources, measurement error and interindividual variability, we also consider uncertainty in the dynamical model itself. To this end, we extend the ordinary differential equation setting used in nonlinear mixed effects models to include stochastic differential equations. The approximate population likelihood is derived using the first-order conditional estimation with interaction method and extended Kalman filtering. To illustrate the application of the stochastic differential mixed effects model, two pharmacokinetic models are considered. First, we use a stochastic one-compartmental model with first-order input and nonlinear elimination to generate synthetic data in a simulated study. We show that by using the proposed method, the three sources of variability can be successfully separated. If the stochastic part is neglected, the parameter estimates become biased, and the measurement error variance is significantly overestimated. Second, we consider an extension to a stochastic pharmacokinetic model in a preclinical study of nicotinic acid kinetics in obese Zucker rats. The parameter estimates are compared between a deterministic and a stochastic NiAc disposition model, respectively. Discrepancies between model predictions and observations, previously described as measurement noise only, are now separated into a comparatively lower level of measurement noise and a significant uncertainty in model dynamics. These examples demonstrate that stochastic differential mixed effects models are useful tools for identifying incomplete or inaccurate model dynamics and for reducing potential bias in parameter estimates due to such model deficiencies.

Effects of keratinocyte growth factor on skin epithelial differentiation of human amnion epithelial cells.

PubMed

Fatimah, Simat Siti; Tan, Geok Chin; Chua, Kienhui; Tan, Ay Eeng; Nur Azurah, Abdul Ghani; Hayati, Abdul Rahman

2013-08-01

The aim of the present study was to determine the effects of KGF on the differentiation of cultured human amnion epithelial cells (HAECs) towards skin keratinocyte. HAECs at passage 1 were cultured in medium HAM's F12: Dulbecco's Modified Eagles Medium (1:1) supplemented with different concentrations of KGF (0, 5, 10, 20, 30 and 50 ng/ml KGF). Dose-response of KGF on HAECs was determined by morphological assessment; growth kinetic evaluation; immunocytochemical analysis; stemness and epithelial gene expression quantification with two step real time RT-PCR. KGF promotes the proliferation of HAECs with maximal effect observed at 10 ng/ml KGF. However, KGF decreased the stemness genes expression: Oct-3/4, Sox-2, Nanog3, Rex-1, FGF-4, FZD-9 and BST-1. KGF also down-regulates epithelial genes expression: CK3, CK18, CK19, Integrin-β1, p63 and involucrin in cultured HAECs. No significant difference on the gene expression was detected for each Nestin, ABCG-2, CK1 and CK14 in KGF-treated HAECs. Immunocytochemical analysis for both control and KGF-treated HAECs demonstrated positive staining against CK14 and CK18 but negative staining against involucrin. The results suggested that KGF stimulates an early differentiation of HAECs towards epidermal cells. Differentiation of KGF-treated HAECs to corneal lineage is unfavourable. Therefore, further studies are needed to elucidate the roles of KGF in the differentiation of HAECs towards skin keratinocytes. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

Cannabidiol Exposure During Neuronal Differentiation Sensitizes Cells Against Redox-Active Neurotoxins.

PubMed

Schönhofen, Patrícia; de Medeiros, Liana M; Bristot, Ivi Juliana; Lopes, Fernanda M; De Bastiani, Marco A; Kapczinski, Flávio; Crippa, José Alexandre S; Castro, Mauro Antônio A; Parsons, Richard B; Klamt, Fábio

2015-08-01

Cannabidiol (CBD), one of the most abundant Cannabis sativa-derived compounds, has been implicated with neuroprotective effect in several human pathologies. Until now, no undesired side effects have been associated with CBD. In this study, we evaluated CBD's neuroprotective effect in terminal differentiation (mature) and during neuronal differentiation (neuronal developmental toxicity model) of the human neuroblastoma SH-SY5Y cell line. A dose-response curve was performed to establish a sublethal dose of CBD with antioxidant activity (2.5 μM). In terminally differentiated SH-SY5Y cells, incubation with 2.5 μM CBD was unable to protect cells against the neurotoxic effect of glycolaldehyde, methylglyoxal, 6-hydroxydopamine, and hydrogen peroxide (H2O2). Moreover, no difference in antioxidant potential and neurite density was observed. When SH-SY5Y cells undergoing neuronal differentiation were exposed to CBD, no differences in antioxidant potential and neurite density were observed. However, CBD potentiated the neurotoxicity induced by all redox-active drugs tested. Our data indicate that 2.5 μM of CBD, the higher dose tolerated by differentiated SH-SY5Y neuronal cells, does not provide neuroprotection for terminally differentiated cells and shows, for the first time, that exposure of CBD during neuronal differentiation could sensitize immature cells to future challenges with neurotoxins.

The Effect of Quercetin on the Osteogenesic Differentiation and Angiogenic Factor Expression of Bone Marrow-Derived Mesenchymal Stem Cells

PubMed Central

Zhou, Yuning; Wu, Yuqiong; Jiang, Xinquan; Zhang, Xiuli; Xia, Lunguo; Lin, Kaili; Xu, Yuanjin

2015-01-01

Bone marrow-derived mesenchymal stem cells (BMSCs) are widely used in regenerative medicine in light of their ability to differentiate along the chondrogenic and osteogenic lineages. As a type of traditional Chinese medicine, quercetin has been preliminarily reported to promote osteogenic differentiation in osteoblasts. In the present study, the effects of quercetin on the proliferation, viability, cellular morphology, osteogenic differentiation and angiogenic factor secretion of rat BMSCs (rBMSCs) were examined by MTT assay, fluorescence activated cell sorter (FACS) analysis, real-time quantitative PCR (RT-PCR) analysis, alkaline phosphatase (ALP) activity and calcium deposition assays, and Enzyme-linked immunosorbent assay (ELISA). Moreover, whether mitogen-activated protein kinase (MAPK) signaling pathways were involved in these processes was also explored. The results showed that quercetin significantly enhanced the cell proliferation, osteogenic differentiation and angiogenic factor secretion of rBMSCs in a dose-dependent manner, with a concentration of 2 μM achieving the greatest stimulatory effect. Moreover, the activation of the extracellular signal-regulated protein kinases (ERK) and p38 pathways was observed in quercetin-treated rBMSCs. Furthermore, these induction effects could be repressed by either the ERK inhibitor PD98059 or the p38 inhibitor SB202190, respectively. These data indicated that quercetin could promote the proliferation, osteogenic differentiation and angiogenic factor secretion of rBMSCs in vitro, partially through the ERK and p38 signaling pathways. PMID:26053266

Effects of sulforaphane on neural stem cell proliferation and differentiation.

PubMed

Han, Zhenxian; Xu, Qian; Li, Changfu; Zhao, Hong

2017-03-01

Sulforaphane (SFN) is a natural organosulfur compound with anti-oxidant and anti-inflammation properties. The objective of this study is to investigate the effect of SFN on the proliferation and differentiation of neural stem cells (NSC). NSCs were exposed to SFN at the concentrations ranging from 0.25 to 10 µM. Cell viability was evaluated with MTT assay and lactate dehydogenase (LDH) release assay. The proliferation of NSCs was evaluated with neurosphere formation assay and Ki-67 staining. The level of Tuj-1 was evaluated with immunostaining and Western blot to assess NSC neuronal differentiation. The expression of key proteins in the Wnt signaling pathway, including β-catenin and cyclin D1, in response to SFN treatment or the Wnt inhibitor, DKK-1, was determined by Western blotting. No significant cytotoxicity was seen for SFN on NSCs with SFN at concentrations of less than 10 µM. On the contrary, SFN of low concentrations stimulated cell proliferation and prominently increased neurosphere formation and NSC differentiation to neurons. SFN treatment upregulated Wnt signaling in the NSCs, whereas DKK-1 attenuated the effects of SFN. SFN is a drug to promote NSC proliferation and neuronal differentiation when used at low concentrations. These protective effects are mediated by Wnt signaling pathway. © 2017 Wiley Periodicals, Inc.

A demonstration test of the dual-beam polarimetry differential imaging system for the high-contrast observation

NASA Astrophysics Data System (ADS)

Dou, Jiangpei; Ren, Deqing; Zhu, Yongtian; Wang, Xue; Zhang, Xi; Li, Rong

2012-09-01

We propose a dual-beam polarimetry differential imaging test system that can be used for the direct imaging of the exoplanets. The system is composed of a liquid crystal variable retarder (LCVR) in the pupil to switch between two orthogonal polarized states, and a Wollaston prism (WP) that will be inserted before the final focal focus of the system to create two polarized images for the differential subtraction. Such a system can work separately or be integrated in the coronagraph system to enhance the high-contrast imaging. To demonstrate the feasibility of the proposed system, here we show the initial test result both with and without integrating our developed coronagraph. A unique feature for this system is that each channel can subtract with itself by using the retarder to rotate the planet's polarization orientation, which has the best performance according to our lab test results. Finally, it is shown that the polarimetry differential imaging system is a promising technique and can be used for the direct imaging observation of reflected lights from the exoplanets.

The mere exposure effect is differentially sensitive to different judgment tasks.

PubMed

Seamon, J G; McKenna, P A; Binder, N

1998-03-01

The mere exposure effect is the increase in positive affect that results from the repeated exposure to previously novel stimuli. We sought to determine if judgments other than affective preference could reliably produce a mere exposure effect for two-dimensional random shapes. In two experiments, we found that brighter and darker judgments did not differentiate target from distracter shapes, liking judgments led to target selection greater than chance, and disliking judgments led to distracter selection greater than chance. These results for brighter, darker, and liking judgments were obtained regardless of whether shape recognition was greater (Experiment 1) or not greater (Experiment 2) than chance. Effects of prior exposure to novel shapes were reliably observed only for affective judgment tasks. These results are inconsistent with general predictions made by the nonspecific activation hypothesis, but not the affective primacy or perceptual fluency hypotheses which were discussed in terms of cognitive neuroscience research. Copyright 1998 Academic Press.

Identification of Centella asiatica's Effective Ingredients for Inducing the Neuronal Differentiation.

PubMed

Jiang, Hui; Zheng, Guoshuai; Lv, Junwei; Chen, Heyu; Lin, Jinjin; Li, Yiyang; Fan, Guorong; Ding, Xianting

2016-01-01

Centella asiatica, commonly known as Gotu kola, has been widely used as a traditional herb for decades. Yet, the study on which compounds or compound combinations actually lead to its brain benefits remains scarce. To study the neuroprotection effects of Centella asiatica, neuronal differentiation of PC12 cells was applied. In our pilot study, we isolated 45 Centella asiatica fractions and tested their abilities for inducing neuronal differentiation on PC12 cells. The most effective fraction showed robust induction in neurite outgrowth and neurofilament expression. LC-MS fingerprint analysis of this fraction revealed asiatic acid and madecassic acid as the dominant components. A further investigation on the pure combination of these two compounds indicated that the combination of these two compounds extensively promoted nerve differentiation in vitro. Application of PD98059, a protein MEK inhibitor, attenuated combination-induced neurofilament expression, indicating the combination-induced nerve differentiation through activation of MEK signaling pathway. Our results support the use of combination of asiatic acid and madecassic acid as an effective mean to intervene neurodegenerative diseases in which neurotrophin deficiency is involved.

Identification of Centella asiatica's Effective Ingredients for Inducing the Neuronal Differentiation

PubMed Central

Jiang, Hui; Zheng, Guoshuai; Lv, Junwei; Chen, Heyu; Lin, Jinjin; Li, Yiyang; Fan, Guorong

2016-01-01

Centella asiatica, commonly known as Gotu kola, has been widely used as a traditional herb for decades. Yet, the study on which compounds or compound combinations actually lead to its brain benefits remains scarce. To study the neuroprotection effects of Centella asiatica, neuronal differentiation of PC12 cells was applied. In our pilot study, we isolated 45 Centella asiatica fractions and tested their abilities for inducing neuronal differentiation on PC12 cells. The most effective fraction showed robust induction in neurite outgrowth and neurofilament expression. LC-MS fingerprint analysis of this fraction revealed asiatic acid and madecassic acid as the dominant components. A further investigation on the pure combination of these two compounds indicated that the combination of these two compounds extensively promoted nerve differentiation in vitro. Application of PD98059, a protein MEK inhibitor, attenuated combination-induced neurofilament expression, indicating the combination-induced nerve differentiation through activation of MEK signaling pathway. Our results support the use of combination of asiatic acid and madecassic acid as an effective mean to intervene neurodegenerative diseases in which neurotrophin deficiency is involved. PMID:27446228

Differential effects of non-informative vision and visual interference on haptic spatial processing

PubMed Central

van Rheede, Joram J.; Postma, Albert; Kappers, Astrid M. L.

2008-01-01

The primary purpose of this study was to examine the effects of non-informative vision and visual interference upon haptic spatial processing, which supposedly derives from an interaction between an allocentric and egocentric reference frame. To this end, a haptic parallelity task served as baseline to determine the participant-dependent biasing influence of the egocentric reference frame. As expected, large systematic participant-dependent deviations from veridicality were observed. In the second experiment we probed the effect of non-informative vision on the egocentric bias. Moreover, orienting mechanisms (gazing directions) were studied with respect to the presentation of haptic information in a specific hemispace. Non-informative vision proved to have a beneficial effect on haptic spatial processing. No effect of gazing direction or hemispace was observed. In the third experiment we investigated the effect of simultaneously presented interfering visual information on the haptic bias. Interfering visual information parametrically influenced haptic performance. The interplay of reference frames that subserves haptic spatial processing was found to be related to both the effects of non-informative vision and visual interference. These results suggest that spatial representations are influenced by direct cross-modal interactions; inter-participant differences in the haptic modality resulted in differential effects of the visual modality. PMID:18553074

Effect of erythropoietin on mesenchymal stem cell differentiation and secretion in vitro in an acute kidney injury microenvironment.

PubMed

Liu, N M; Tian, J; Wang, W W; Han, G F; Cheng, J; Huang, J; Zhang, J Y

2013-02-28

We investigated the effect of erythropoietin (EPO) on differentiation and secretion of bone marrow-derived mesenchymal stem cells in an acute kidney injury microenvironment. Acute kidney injury mouse models were prepared. Both renal cortices were then immediately collected to produce the ischemia/reperfusion kidney homogenate supernatant. The morphological and ultrastructural changes in the cells were observed using an inverted microscope and a transmission electron microscope. Cytokeratin-18 was detected using flow cytometry. Bone morphogenetic protein-7 levels, hepatocyte growth factor, and vascular endothelial growth factor in the culture medium were detected using an enzyme-linked immunosorbent assay. The cells had high CD29 and CD44 expression, as well as low CD34 and CD45 expression. More round and oval cells with cobble-like appearances were observed after EPO treatment. In addition, an increase in the number of rough endoplasmic reticula, lysosomes, and mitochondria was observed in the cytoplasm; the intercellular junction peculiar to epithelial cells was also seen on the cell surface. After treatment with ischemia/reperfusion kidney homogenate supernatant, cytokeratin-18 expression increased significantly and EPO could magnify its expression. Bone morphogenetic protein-7 levels, hepatocyte growth factor, and vascular endothelial growth factor levels after treatment with ischemia/reperfusion kidney homogenate supernatant significantly decreased, whereas EPO increased the cytokine secretion. The acute kidney injury microenvironment can induce the bone marrow-derived mesenchymal stem cells to partially differentiate into renal tubular epithelium-shaped cells, but weaken their secretion function. EPO intervention can boost up their differentiation function and reverse their low secretion effect.

Two-Time Scale Virtual Sensor Design for Vibration Observation of a Translational Flexible-Link Manipulator Based on Singular Perturbation and Differential Games

PubMed Central

Ju, Jinyong; Li, Wei; Wang, Yuqiao; Fan, Mengbao; Yang, Xuefeng

2016-01-01

Effective feedback control requires all state variable information of the system. However, in the translational flexible-link manipulator (TFM) system, it is unrealistic to measure the vibration signals and their time derivative of any points of the TFM by infinite sensors. With the rigid-flexible coupling between the global motion of the rigid base and the elastic vibration of the flexible-link manipulator considered, a two-time scale virtual sensor, which includes the speed observer and the vibration observer, is designed to achieve the estimation for the vibration signals and their time derivative of the TFM, as well as the speed observer and the vibration observer are separately designed for the slow and fast subsystems, which are decomposed from the dynamic model of the TFM by the singular perturbation. Additionally, based on the linear-quadratic differential games, the observer gains of the two-time scale virtual sensor are optimized, which aims to minimize the estimation error while keeping the observer stable. Finally, the numerical calculation and experiment verify the efficiency of the designed two-time scale virtual sensor. PMID:27801840

The effects of crises on differential mortality by sex in Bangladesh.

PubMed

Langsten, R

1981-01-01

Although the data available for secondary analysis are not ideal for the task at hand, they confirm that in normal times Bangladesh conforms to the South Asian pattern of sex differentials in mortality with females generally having higher death rates, and they clearly show that, in crisis years, the differential is inverted, with males in certain age groups suffering disproportionate increases in mortality. This crisis effect on sex differentials in mortality has been noted previously and on this point all observers appear to agree. Disagreement arises, however, as to the reasons why death rates among males increase more than those of females in crisis years. Explanations offered previously are either contradicted by available evidence or appear to be, at best, partial reasons for changes in some age groups. This paper reviews a number of suggested explanations, both cultural and demographic, which may provide an understanding of the mechanisms by which the normal sex specific mortality differentials are reversed at times of crisis. Some existing data, not currently available for detailed analysis, may be useful in examining some of the suggested reasons, particularly the demographic reasons. In the absence of far more information about intrafamilial decision making processes and how these may change in times of crisis, it is impossible to understand fully the reasons for changes in the mortality disadvantage. While the strong cultural bias favoring males offers a reason for lower male mortality, likely intervening variables such as nutrition and use of health facilities show only modest evidence of this bias. Crisis situations are those caused by war, severe flooding, price changes, and cyclones or other severe weather patterns, all of which impact on food production and access to health care.

Differential parenting and children's behavioral problems: curvilinear associations and mother-father combined effects.

PubMed

Meunier, Jean Christophe; Bisceglia, Rossana; Jenkins, Jennifer M

2012-07-01

In this study the associations between mothers' and fathers' differential parenting and children's oppositional and emotional problems were examined. A curvilinear relationship between differential parenting and children's outcomes was hypothesized, as well as the combined effect of mothers' and fathers' parenting. Data came from a community sample of 599 two-parent families with multiple children per family and were analyzed using a cross-classified multilevel model. Results showed that both family average parenting and differential parenting explained unique variance in children's outcomes. The curvilinear hypothesis was supported for oppositional behavior but not for emotional problems. The effects of mother and father positivity were found to be additive for both family average parenting and differential parenting, but for negativity there was evidence for multiplicative effects.

Differential Effects of Arousal in Positive and Negative Autobiographical Memories

PubMed Central

Ford, Jaclyn Hennessey; Addis, Donna Rose; Giovanello, Kelly S.

2014-01-01

Autobiographical memories are characterized by a range of emotions and emotional reactions. Recent research has demonstrated that differences in emotional valence (positive v. negative emotion) and arousal (the degree of emotional intensity) differentially influence the retrieved memory narrative. Although the mnemonic effects of valence and arousal have both been heavily studied, it is currently unclear whether the effects of emotional arousal are equivalent for positive and negative autobiographical events. In the current study, multilevel models were used to examine differential effects emotional valence and arousal on the richness of autobiographical memory retrieval both between and within subjects. Thirty-four young adults were asked to retrieve personal autobiographical memories associated with popular musical cues and to rate the valence, arousal, and richness of these events. The multilevel analyses identified independent influences of valence and intensity upon retrieval characteristics at the within and between subject levels. In addition, the within subject interactions between valence and arousal highlighted differential effects of arousal for positive and negative memories. These findings have important implications for future studies of emotion and memory, highlighting the importance of considering both valence and arousal when examining the role emotion plays in the richness of memory representation. PMID:22873402

Differential effects of arousal in positive and negative autobiographical memories.

PubMed

Ford, Jaclyn Hennessey; Addis, Donna Rose; Giovanello, Kelly S

2012-01-01

Autobiographical memories are characterised by a range of emotions and emotional reactions. Recent research has demonstrated that differences in emotional valence (positive vs. negative emotion) and arousal (the degree of emotional intensity) differentially influence the retrieved memory narrative. Although the mnemonic effects of valence and arousal have both been heavily studied, it is currently unclear whether the effects of emotional arousal are equivalent for positive and negative autobiographical events. In the current study, multilevel models were used to examine differential effects of emotional valence and arousal on the richness of autobiographical memory retrieval both between and within subjects. Thirty-four young adults were asked to retrieve personal autobiographical memories associated with popular musical cues and to rate the valence, arousal and richness of these events. The multilevel analyses identified independent influences of valence and intensity upon retrieval characteristics at the within- and between-subject levels. In addition, the within-subject interactions between valence and arousal highlighted differential effects of arousal for positive and negative memories. These findings have important implications for future studies of emotion and memory, highlighting the importance of considering both valence and arousal when examining the role emotion plays in the richness of memory representation.

DIFFERENTIAL KILLING EFFECT IN JUTE BY X-RAYS AND RADIOISOTOPES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Basu, R.K.

1962-01-01

Treatments with x rays and BETA rays from P/sup 32/ and S/sup 35/ on dry and pure line seeds of three varieties of Corchorus olitorius L. and two varieties of C. capsularis L. produced differential killing effect. 0ver the range of dosages applied treatments with P/sup 32/ and S/sup 35/ showed lesser killing effect than treatments with x rays. From the counts of survivals at maturity, the LD/sub 50/with x rays was found to lie between 64000 and r0000 r for the varieties of C. olitorius and between 80000 and 90000 r for the varieties of C. capsularis. While themore » usual relationship of decrease in survival with increase in dosage was established with x rays, treatments with P/sup 32/ and S/ sup 35/ often showed increased survival compared to the control. The differential killing effect of the three mutagens is discussed as a consequence of difference in ion density. The obscure effects of radioisotopes may be due to production of substances reacting in the form of stimulation or protective agents. The differential radiosensitivity of the two species may be due to difference in factors like seed size and thickness of seed coat, which influence the non- genetical effects of irradiation. (auth)« less

Interacting effects of latitude, mass, age, and sex on winter survival of Surf Scoters (Melanitta perspicillata): Implications for differential migration

USGS Publications Warehouse

Uher-Koch, Brian D.; Esler, Daniel N.; Iverson, Samuel A.; Ward, David; Boyd, Sean; Kirk, Molly; Lewis, Tyler L.; VanStratt, Corey S.; Brodhead, Katherine M.; Hupp, Jerry W.; Schmutz, Joel A.

2016-01-01

We quantified variation in winter survival of Surf Scoters (Melanitta perspicillata (L., 1758)) across nearly 30° of latitude on the Pacific coast of North America to evaluate potential effects on winter distributions, including observed differential distributions of age and sex classes. We monitored fates of 297 radio-marked Surf Scoters at three study sites: (1) near the northern periphery of their wintering range in southeast Alaska, USA, (2) the range core in British Columbia, Canada, and (3) the southern periphery in Baja California, Mexico. We detected 34 mortalities and determined that survival averaged lower at the range peripheries than in the range core, was lower during mid-winter than during late winter at all sites, and was positively correlated with body mass within locations. Although neither age nor sex class had direct effects, mass effects led to differential survival patterns among classes. When simultaneously incorporating these interacting influences, adult males of mean mass for their location had highest survival at the northern range periphery in Alaska, whereas adult females and juveniles had higher survival at the range core and the southern periphery. Our observations help to explain patterns of differential migration and distribution reported for this species and highlight seasonal periods (mid-winter) and locations (range peripheries) of elevated levels of mortality for demographically important age–sex classes (adult females).

Effect of Wnt-1 inducible signaling pathway protein-2 (WISP-2/CCN5), a downstream protein of Wnt signaling, on adipocyte differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inadera, Hidekuni; Shimomura, Akiko; Tachibana, Shinjiro

2009-02-20

Wnt signaling negatively regulates adipocyte differentiation, and ectopic expression of Wnt-1 in 3T3-L1 cells induces several downstream molecules of Wnt signaling, including Wnt-1 inducible signaling pathway protein (WISP)-2. In this study, we examined the role of WISP-2 in the process of adipocyte differentiation using an in vitro cell culture system. In the differentiation of 3T3-L1 cells, WISP-2 expression was observed in growing cells and declined thereafter. In the mitotic clonal expansion phase of adipocyte differentiation, WISP-2 expression was transiently down-regulated concurrently with up-regulation of CCAAT/enhancer-binding protein {delta} expression. Treatment of 3T3-L1 cells in the differentiation medium with lithium, an activatormore » of Wnt signaling, inhibited the differentiation process with concomitant induction of WISP-2. Treatment of differentiated cells with lithium induced de-differentiation as evidenced by profound reduction of peroxisome proliferator-activator receptor {gamma} expression and concomitant induction of WISP-2. However, de-differentiation of differentiated cells induced by tumor necrosis factor-{alpha} did not induce WISP-2 expression. To directly examine the effect of WISP-2 on adipocyte differentiation, 3T3-L1 cells were infected with a retrovirus carrying WISP-2. Although forced expression of WISP-2 inhibited preadipocyte proliferation, it had no effect on adipocyte differentiation. Thus, although WISP-2 is a downstream protein of Wnt signaling, the role of WISP-2 on adipocyte differentiation may be marginal, at least in this in vitro culture model.« less

Thrombopoietin has a differentiative effect on late-stage human erythropoiesis.

PubMed

Liu, W; Wang, M; Tang, D C; Ding, I; Rodgers, G P

1999-05-01

To further explore the mechanism of the effect of thrombopoietin (TPO) on erythropoiesis, we used a two-phase culture system to investigate the effect of TPO on late-stage human erythroid lineage differentiation. In serum-free suspension and semisolid cultures of human peripheral blood derived erythroid progenitors, TPO alone did not produce benzidine-positive cells. However, in serum-containing culture, TPO alone stimulated erythroid cell proliferation and differentiation, demonstrated by erythroid colony formation, production of benzidine-positive cells and haemoglobin (Hb) synthesis. Monoclonal anti-human erythropoietin antibody and anti-human erythropoietin receptor antibody completely abrogated the erythroid differentiative ability of TPO in the serum-containing systems. This implied that binding of EPO and EPO-R was essential for erythropoiesis and the resultant signal transduction may be augmented by the signals emanating from TPO-c-Mpl interaction. Experiment of withdrawal of TPO further demonstrated the involvement of TPO in late-stage erythropoiesis. RT-PCR results showed that there was EPO-R but not c-Mpl expression on developing erythroblasts induced by TPO in serum-containing system. Our results establish that TPO affects not only the proliferation of erythroid progenitors but also the differentiation of erythroid progenitors to mature erythroid cells.

Assessing the Sensitivity of Treatment Effect Estimates to Differential Follow-Up Rates: Implications for Translational Research

PubMed Central

McCaffrey, Daniel; Ramchand, Rajeev; Hunter, Sarah B.; Suttorp, Marika

2012-01-01

We develop a new tool for assessing the sensitivity of findings on treatment effectiveness to differential follow-up rates in the two treatment conditions being compared. The method censors the group with the higher response rate to create a synthetic respondent group that is then compared with the observed cases in the other condition to estimate a treatment effect. Censoring is done under various assumptions about the strength of the relationship between follow-up and outcomes to determine how informative differential dropout can alter inferences relative to estimates from models that assume the data are missing at random. The method provides an intuitive measure for understanding the strength of the association between outcomes and dropout that would be required to alter inferences about treatment effects. Our approach is motivated by translational research in which treatments found to be effective under experimental conditions are tested in standard treatment conditions. In such applications, follow-up rates in the experimental setting are likely to be substantially higher than in the standard setting, especially when observational data are used in the evaluation. We test the method on a case study evaluation of the effectiveness of an evidence-supported adolescent substance abuse treatment program (Motivational Enhancement Therapy/Cognitive Behavioral Therapy-5 [MET/CBT-5]) delivered by community-based treatment providers relative to its performance in a controlled research trial. In this case study, follow-up rates in the community based settings were extremely low (54%) compared to the experimental setting (95%) giving raise to concerns about non-ignorable drop-out. PMID:22956890

Differential effects of formononetin and cladrin on osteoblast function, peak bone mass achievement and bioavailability in rats.

PubMed

Gautam, Abnish K; Bhargavan, Biju; Tyagi, Abdul M; Srivastava, Kamini; Yadav, Dinesh K; Kumar, Manmeet; Singh, Akanksha; Mishra, Jay S; Singh, Amar Bahadur; Sanyal, Sabyasachi; Maurya, Rakesh; Manickavasagam, Lakshmi; Singh, Sheelendra P; Wahajuddin, Wahajuddin; Jain, Girish K; Chattopadhyay, Naibedya; Singh, Divya

2011-04-01

Dietary soy isoflavones including genistein and daidzein have been shown to have favorable effects during estrogen deficiency in experimental animals and humans. We have evaluated osteogenic effect of cladrin and formononetin, two structurally related methoxydaidzeins found in soy food and other natural sources. Cladrin, at as low as 10 nM, maximally stimulated both osteoblast proliferation and differentiation by activating MEK-Erk pathway. On the other hand, formononetin maximally stimulated osteoblast differentiation at 100 nM that involved p38 MAPK pathway but had no effect on osteoblast proliferation. Unlike daidzein, these two compounds neither activated estrogen receptor in osteoblast nor had any effect on osteoclast differentiation. Daily oral administration of each of these compounds at 10.0 mg kg(-1) day(-1) dose to recently weaned female Sprague-Dawley rats for 30 consecutive days, increased bone mineral density at various anatomic positions studied. By dynamic histomorphometry of bone, we observed that rats treated with cladrin exhibited increased mineral apposition and bone formation rates compared with control, while formononetin had no effect. Cladrin had much better plasma bioavailability compared with formononetin. None of these compounds exhibited estrogen agonistic effect in uteri. Our data suggest that cladrin is more potent among the two in promoting parameters of peak bone mass achievement, which could be attributed to its stimulatory effect on osteoblast proliferation and better bioavailability. To the best of our knowledge, this is the first attempt to elucidate structure-activity relationship between the methoxylated forms of daidzein and their osteogenic effects. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of gold nanoparticles on adipogenic differentiation of human mesenchymal stem cells

NASA Astrophysics Data System (ADS)

Kohl, Yvonne; Gorjup, Erwin; Katsen-Globa, Alisa; Büchel, Claudia; von Briesen, Hagen; Thielecke, Hagen

2011-12-01

Gold nanoparticles are very attractive for biomedical products. However, there is a serious lack of information concerning the biological activity of nanosized gold in human tissue cells. An influence of nanoparticles on stem cells might lead to unforeseen consequences to organ and tissue functions as long as all cells arising from the initial stem cell might be subsequently damaged. Therefore the effect of negatively charged gold nanoparticles (9 and 95 nm), which are certified as reference material for preclinical biomedical research, on the adipogenic differentiation of human mesenchymal stem cells (hMSCs) is investigated here. Bone marrow hMSCs are chosen as differentiation model since bone marrow hMSCs are well characterized and their differentiation into the adipogenic lineage shows clear and easily detectable differentiation. In this study effects of gold nanoparticles on adipogenic differentiation are analyzed regarding fat storage and mitochondrial activity after different exposure times (4-21 days). Using time lapse microscopy the differentiation progress under chronically gold nanoparticle treatment is continuously investigated. In this preliminary study, chronically treatment of adipogenic differentiating hMSCs with gold nanoparticles resulted in a reduced number and size of lipid vacuoles and reduced mitochondrial activity depending on the applied concentration and the surface charge of the particles.

The effect of epidermal growth factor on neonatal incisor differentiation in the mouse.

PubMed

Topham, R T; Chiego, D J; Gattone, V H; Hinton, D A; Klein, R M

1987-12-01

The effect of epidermal growth factor (EGF) on cellular differentiation of the neonatal mouse mandibular incisor was examined autoradiographically using tritiated thymidine ([3H]TDR) and tritiated proline ([3H]PRO). On days 0 (day of birth), 1, and 2, EGF was administered (3 micrograms/g body wt) sc to neonates. Mice were killed on Days 1, 4, 7, 10, and 13 after birth and were injected with either [3H]TDR or [3H]PRO 1 hr before death. [3H]TDR was used to analyze cell proliferation in eight cell types in the developing mouse incisor including upper (lingual) and lower (buccal) pulpal fibroblasts, preodontoblasts, inner and outer enamel epithelial cells (IEE and OEE), stratum intermedium (SI), stellate reticulum (SR), and periodontal ligament (PDL) fibroblasts. [3H]PRO was used to analyze protein synthesis in ameloblasts, and their secretion products (enamel and dentin), as well as PDL fibroblasts. The selected EGF injection scheme elicited acceleration of incisor eruption with minimal growth retardation. At Day 1, the upper and lower pulp, preodontoblasts, SI, and SR showed a significant decrease in labeling index (LI) 24 hr after a single EGF injection. After multiple injections (Days 0, 1, 2), two LI patterns were observed. In lower pulp, preodontoblasts, IEE, SI, SR, and OEE, a posteruptive change in LI was observed. In contrast, the upper pulp and PDL regions demonstrated a direct temporal relationship with eruption. Autoradiographic analysis with [3H]PRO indicated that EGF treatment caused significant increases in grain counts per unit area in ameloblast, odontoblast, and PDL regions studied. Significant differences were found in all four regions studied (ameloblasts, enamel, odontoblasts, dentin) at the 45-microns-tall ameloblast level as well as ameloblasts and odontoblasts at the 30-microns level at 13 days of age. The PDL demonstrated significant differences at all locations studied (base, 30 microns, 45 microns,) in 4-, 7-, and 13-day-old mice

Differentiating Performance Approach Goals and Their Unique Effects

ERIC Educational Resources Information Center

Edwards, Ordene V.

2014-01-01

The study differentiates between two types of performance approach goals (competence demonstration performance approach goal and normative performance approach goal) by examining their unique effects on self-efficacy, interest, and fear of failure. Seventy-nine students completed questionnaires that measure performance approach goals,…

Effects of quercetin, a natural phenolic compound, in the differentiation of human mesenchymal stem cells (MSC) into adipocytes and osteoblasts.

PubMed

Casado-Díaz, Antonio; Anter, Jaouad; Dorado, Gabriel; Quesada-Gómez, José Manuel

2016-06-01

Natural phenols may have beneficial properties against oxidative stress, which is associated with aging and major chronic aging-related diseases, such as loss of bone mineral mass (osteoporosis) and diabetes. The main aim of this study was to analyze the effect of quercetin, a major nutraceutical compound present in the "Mediterranean diet", on mesenchymal stem-cell (MSC) differentiation. Such cells were induced to differentiate into osteoblasts or adipocytes in the presence of two quercetin concentrations (0.1 and 10μM). Several physiological parameters and the expression of osteoblastogenesis and adipogenesis marker genes were monitored. Quercetin (10μM) inhibited cell proliferation, alkaline phosphatase (ALPL) activity and mineralization, down-regulating the expression of ALPL, collagen type I alpha 1 (COL1A1) and osteocalcin [bone gamma-carboxyglutamate protein (BGLAP)] osteoblastogenesis-related genes in MSC differentiating into osteoblasts. Moreover, in these cultures, CCAAT/enhancer-binding protein alpha (CEBPA) and peroxisome proliferator-activated receptor gamma 2 (PPARG2) adipogenic genes were induced, and cells differentiated into adipocytes were observed. Quercetin did not affect proliferation, but increased adipogenesis, mainly at 10-μM concentration in MSC induced to differentiate to adipocytes. β- and γ-catenin (plakoglobin) nuclear levels were reduced and increased, respectively, in quercetin-treated cultures. This suggests that the effect of high concentration of quercetin on MSC osteoblastic and adipogenic differentiation is mediated via Wnt/β-catenin inhibition. In conclusion, quercetin supplementation inhibited osteoblastic differentiation and promoted adipogenesis at the highest tested concentration. Such possible adverse effects of high quercetin concentrations should be taken into account in nutraceutical or pharmaceutical strategies using such flavonol. Copyright © 2016 Elsevier Inc. All rights reserved.

Inflammatory parameters in Caco-2 cells: effect of stimuli nature, concentration, combination and cell differentiation.

PubMed

Van De Walle, Jacqueline; Hendrickx, Aurélie; Romier, Béatrice; Larondelle, Yvan; Schneider, Yves-Jacques

2010-08-01

Enterocytes regulate gut maintenance and defence by secreting and responding to inflammatory mediators and by modulating the intestinal epithelial permeability. In order to develop an in vitro model of the acute phase of intestinal inflammation, Caco-2 cells were exposed to the inflammatory mediators IL-1beta, TNF-alpha, IFN-gamma and LPS, and the importance of several experimental parameters, i.e. cell differentiation, stimulus nature, concentration and combination on the inflammatory response was assessed by measuring the production of IL-6, IL-8, PGE-2 and NO and by evaluating the monolayer permeability. A maximal increase in IL-8, IL-6 and PGE-2 production and monolayer permeability was observed when using the cytokines simultaneously at their highest level, but this relied mainly on IL-1beta. The effects of TNF-alpha on IL-8 and IL-6 or NO production were stronger upon combination with IL-1beta or IFN-gamma, respectively, whereas cells were unaffected by the presence of LPS. Although NO production, induced by IFN-gamma-containing combinations, was observed only in differentiated cells, general inflammatory response was higher in proliferating cells. The use of a mixture of IL-1beta, TNF-alpha and IFN-gamma thus accurately mimics intestinal inflammatory processes, but cell differentiation and stimuli combination are important parameters to take into account for in vitro studies on intestinal inflammation. Copyright (c) 2010. Published by Elsevier Ltd.

The effect of dexamethasone and triiodothyronine on terminal differentiation of primary bovine chondrocytes and chondrogenically differentiated mesenchymal stem cells.

PubMed

Randau, Thomas M; Schildberg, Frank A; Alini, Mauro; Wimmer, Matthias D; Haddouti, El-Mustapha; Gravius, Sascha; Ito, Keita; Stoddart, Martin J

2013-01-01

The newly evolved field of regenerative medicine is offering solutions in the treatment of bone or cartilage loss and deficiency. Mesenchymal stem cells, as well as articular chondrocytes, are potential cells for the generation of bone or cartilage. The natural mechanism of bone formation is that of endochondral ossification, regulated, among other factors, through the hormones dexamethasone and triiodothyronine. We investigated the effects of these hormones on articular chondrocytes and chondrogenically differentiated mesenchymal stem cells, hypothesizing that these hormones would induce terminal differentiation, with chondrocytes and differentiated stem cells being similar in their response. Using a 3D-alginate cell culture model, bovine chondrocytes and chondrogenically differentiated stem cells were cultured in presence of triiodothyronine or dexamethasone, and cell proliferation and extracellular matrix production were investigated. Collagen mRNA expression was measured by real-time PCR. Col X mRNA and alkaline phosphatase were monitored as markers of terminal differentiation, a prerequisite of endochondral ossification. The alginate culture system worked well, both for the culture of chondrocytes and for the chondrogenic differentiation of mesenchymal stem cells. Dexamethasone led to an increase in glycosaminoglycan production. Triiodothyronine increased the total collagen production only in chondrocytes, where it also induced signs of terminal differentiation, increasing both collagen X mRNA and alkaline phosphatase activity. Dexamethasone induced terminal differentiation in the differentiated stem cells. The immature articular chondrocytes used in this study seem to be able to undergo terminal differentiation, pointing to their possible role in the onset of degenerative osteoarthritis, as well as their potential for a cell source in bone tissue engineering. When chondrocyte-like cells, after their differentiation, can indeed be moved on towards terminal

Differential effects of the extracellular microenvironment on human embryonic stem cell differentiation into keratinocytes and their subsequent replicative life span.

PubMed

Movahednia, Mohammad Mehdi; Kidwai, Fahad Karim; Zou, Yu; Tong, Huei Jinn; Liu, Xiaochen; Islam, Intekhab; Toh, Wei Seong; Raghunath, Michael; Cao, Tong

2015-04-01

Culture microenvironment plays a critical role in the propagation and differentiation of human embryonic stem cells (hESCs) and their differentiated progenies. Although high efficiency of hESC differentiation to keratinocytes (hESC-Kert) has been achieved, little is known regarding the effects of early culture microenvironment and pertinent extracellular matrix (ECM) interactions during epidermal commitment on subsequent proliferative capacity of hESC-Kert. The aim of this study is to evaluate the effects of the different ECM microenvironments during hESC differentiation on subsequent replicative life span of hESC-Kert. In doing so, H1-hESCs were differentiated to keratinocytes (H1-Kert) in two differentiation systems. The first system employed autologous fibroblast feeder support, in which keratinocytes (H1-Kert(ACC)) were derived by coculture of hESCs with hESC-derived fibroblasts (H1-ebFs). The second system employed a novel decellularized matrix from H1-ebFs to create a dermoepidermal junction-like (DEJ) matrix. H1-Kert(AFF) were derived by differentiation of hESCs on the feeder-free system employing the DEJ matrix. Our study indicated that the feeder-free system with the use of DEJ matrix was more efficient in differentiation of hESCs toward epidermal progenitors. However, the feeder-free system was not sufficient to support the subsequent replicative capacity of differentiated keratinocytes. Of note, H1-Kert(AFF) showed limited replicative capacity with reduced telomere length and early cellular senescence. We further showed that the lack of cell-cell interactions during epidermal commitment led to heightened production of TGF-β1 by hESC-Kert during extended culture, which in turn was responsible for resulting in the limited replicative life span with cellular senescence of hESC-Kert derived under the feeder-free culture system. This study highlights for the first time the importance of the culture microenvironment and cell-ECM interactions during

Bioactive treatment promotes osteoblast differentiation on titanium materials fabricated by selective laser melting technology.

PubMed

Tsukanaka, Masako; Fujibayashi, Shunsuke; Takemoto, Mitsuru; Matsushita, Tomiharu; Kokubo, Tadashi; Nakamura, Takashi; Sasaki, Kiyoyuki; Matsuda, Shuichi

2016-01-01

Selective laser melting (SLM) technology is useful for the fabrication of porous titanium implants with complex shapes and structures. The materials fabricated by SLM characteristically have a very rough surface (average surface roughness, Ra=24.58 µm). In this study, we evaluated morphologically and biochemically the specific effects of this very rough surface and the additional effects of a bioactive treatment on osteoblast proliferation and differentiation. Flat-rolled titanium materials (Ra=1.02 µm) were used as the controls. On the treated materials fabricated by SLM, we observed enhanced osteoblast differentiation compared with the flat-rolled materials and the untreated materials fabricated by SLM. No significant differences were observed between the flat-rolled materials and the untreated materials fabricated by SLM in their effects on osteoblast differentiation. We concluded that the very rough surface fabricated by SLM had to undergo a bioactive treatment to obtain a positive effect on osteoblast differentiation.

The effect of differentiation agents on inflammatory and oxidative responses of the human neuroblastoma cell line SK-N-SH.

PubMed

Niewiarowska-Sendo, Anna; Patrzalek, Katarzyna; Kozik, Andrzej; Guevara-Lora, Ibeth

2015-01-01

Obtaining a suitable experimental cellular model is a major problem for neuroscience studies. Neuroblastoma cell lines have been often applied in studies related to pathological disorders of nervous system. However, in the search for an ideal model, these cells must be differentiated to cancel their tumor character. The subsequent reactions that are caused by differentiation are not always indifferent to the same model. We evaluated the effect of two well known substances, used for SH-N-SK cell line differentiation, retinoic acid (RA) and phorbol-12-myristate-13-acetate (PMA), on the induction of pro-inflammatory and pro-oxidative reactions in these cells. Cells differentiated with PMA were able to produce significantly higher amounts of pro-inflammatory cytokines whereas the release of nitric oxide radicals was similar to that in undifferentiated cells. On the contrary, in RA-differentiated cells no significant changes in cytokine production were observed and the nitric oxide release was decreased. Additionally, the RA-differentiated neuronal model was more sensible to lipopolysaccharide stimulation, producing pro-inflammatory cytokines abundantly. These results suggest that RA-differentiated SH-N-SK cells provide a more suitable experimental model for the study of molecular and cellular mechanisms of the inflammation and oxidative stress in neuronal cells.

Distinguishing differential susceptibility from diathesis-stress: recommendations for evaluating interaction effects.

PubMed

Roisman, Glenn I; Newman, Daniel A; Fraley, R Chris; Haltigan, John D; Groh, Ashley M; Haydon, Katherine C

2012-05-01

This report describes the state of the art in distinguishing data generated by differential susceptibility from diathesis-stress models. We discuss several limitations of existing practices for probing interaction effects and offer solutions that are designed to better differentiate differential susceptibility from diathesis-stress models and quantify their corresponding implications. In addition, we demonstrate the utility of these methods by revisiting published evidence suggesting that temperamental difficulty serves as a marker of enhanced susceptibility to early maternal caregiving across a range of outcome domains in the NICHD Study of Early Child Care and Youth Development. We find that, with the exception of mother reports of psychopathology, there is consistent evidence in the Study of Early Child Care and Youth Development that the predictive significance of early sensitivity is moderated by difficult temperament over time. However, differential susceptibility effects emerged primarily for teacher reports of academic skills, social competence, and symptomatology. In contrast, effects more consistent with the diathesis-stress model were obtained for mother reports of social skills and objective tests of academic skills. We conclude by discussing the value of the application of this work to the next wave of Gene × Environment studies focused on early caregiving experiences.

Quantum Observables and Effect Algebras

NASA Astrophysics Data System (ADS)

Dvurečenskij, Anatolij

2018-03-01

We study observables on monotone σ-complete effect algebras. We find conditions when a spectral resolution implies existence of the corresponding observable. We characterize sharp observables of a monotone σ-complete homogeneous effect algebra using its orthoalgebraic skeleton. In addition, we study compatibility in orthoalgebras and we show that every orthoalgebra satisfying RIP is an orthomodular poset.

Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.

PubMed

Glass, Donald A; Bialek, Peter; Ahn, Jong Deok; Starbuck, Michael; Patel, Millan S; Clevers, Hans; Taketo, Mark M; Long, Fanxin; McMahon, Andrew P; Lang, Richard A; Karsenty, Gerard

2005-05-01

Inactivation of beta-catenin in mesenchymal progenitors prevents osteoblast differentiation; inactivation of Lrp5, a gene encoding a likely Wnt coreceptor, results in low bone mass (osteopenia) by decreasing bone formation. These observations indicate that Wnt signaling controls osteoblast differentiation and suggest that it may regulate bone formation in differentiated osteoblasts. Here, we study later events and find that stabilization of beta-catenin in differentiated osteoblasts results in high bone mass, while its deletion from differentiated osteoblasts leads to osteopenia. Surprisingly, histological analysis showed that these mutations primarily affect bone resorption rather than bone formation. Cellular and molecular studies showed that beta-catenin together with TCF proteins regulates osteoblast expression of Osteoprotegerin, a major inhibitor of osteoclast differentiation. These findings demonstrate that beta-catenin, and presumably Wnt signaling, promote the ability of differentiated osteoblasts to inhibit osteoclast differentiation; thus, they broaden our knowledge of the functions Wnt proteins have at various stages of skeletogenesis.

Concentration-dependent effect of sodium hypochlorite on stem cells of apical papilla survival and differentiation.

PubMed

Martin, David E; De Almeida, Jose Flavio A; Henry, Michael A; Khaing, Zin Z; Schmidt, Christine E; Teixeira, Fabricio B; Diogenes, Anibal

2014-01-01

Intracanal disinfection is a crucial step in regenerative endodontic procedures. Most published cases suggest the use of sodium hypochlorite (NaOCl) as the primary irrigant. However, the effect of clinically used concentrations of NaOCl on the survival and differentiation of stem cells is largely unknown. In this study, we tested the effect of various concentrations of NaOCl on the stem cells of the apical papilla (SCAPs) survival and dentin sialophosphoprotein (DSPP) expression. Standardized root canals were created in extracted human teeth and irrigated with NaOCl (0.5%, 1.5%, 3%, or 6%) followed by 17% EDTA or sterile saline. SCAPs in a hyaluronic acid-based scaffold were seeded into the canals and cultured for 7 days. Next, viable cells were quantified using a luminescence assay, and DSPP expression was evaluated using quantitative real-time polymerase chain reaction. There was a significant reduction in survival and DSPP expression in the group treated with 6% NaOCl compared with the untreated control group. Comparable survival was observed in the groups treated with the lower concentrations of NaOCl, but greater DSPP expression was observed in the 1.5% NaOCl group. In addition, 17% EDTA resulted in increased survival and DSPP expression partially reversing the deleterious effects of NaOCl. Collectively, the results suggest that dentin conditioning with high concentrations of NaOCl has a profound negative effect on the survival and differentiation of SCAPs. However, this effect can be prevented with the use of 1.5% NaOCl followed by 17% EDTA. The inclusion of this irrigation regimen might be beneficial in regenerative endodontic procedures. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Effect of in vitro chondrogenic differentiation of autologous mesenchymal stem cells on cartilage and subchondral cancellous bone repair in osteoarthritis of temporomandibular joint.

PubMed

Chen, K; Man, C; Zhang, B; Hu, J; Zhu, S S

2013-02-01

This study investigated the effects of in vitro chondrogenic differentiated mesenchymal stem cells (MSCs) on cartilage and subchondral cancellous bone in temporomandibular joint osteoarthritis (TMJOA). Four weeks after induction of osteoarthritis (OA), the joints received hylartin solution, non-chondrogenic MSCs or in vitro chondrogenic differentiated MSCs. The changes in cartilage and subchondral cancellous bone were evaluated by histology, reverse transcription polymerase chain reaction and micro-computed tomography (CT). Implanted cells were tracked using Adeno-LacZ labelling. The differentiated MSC-treated group had better histology than the MSC-treated group at 4 and 12 weeks, but no difference at 24 weeks. Increased mRNA expression of collegan II, aggeran, Sox9 and decreased matrix metalloproteinase 13 (MMP13) were observed in differentiated MSC-treated groups compared to the undifferentiated MSC-treated group at 4 weeks. The differentiated MSC-treated group had decreased bone volume fraction, trabecular thickness and bone surface density, and increased trabecular spacing in the subchondral cancellous bone than the undifferentiated MSC-treated group. Transplanted cells were observed at cartilage, subchondral bone, and the synovial membrane lining at 4 weeks. Intra-articular injection of MSCs could delay the progression of TMJOA, and in vitro chondrogenic induction of MSCs could enhance the therapeutic effects. This provides new insights into the role of MSCs in cell-based therapies for TMJOA. Copyright © 2012 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

A modified carrier-to-code leveling method for retrieving ionospheric observables and detecting short-term temporal variability of receiver differential code biases

NASA Astrophysics Data System (ADS)

Zhang, Baocheng; Teunissen, Peter J. G.; Yuan, Yunbin; Zhang, Xiao; Li, Min

2018-03-01

Sensing the ionosphere with the global positioning system involves two sequential tasks, namely the ionospheric observable retrieval and the ionospheric parameter estimation. A prominent source of error has long been identified as short-term variability in receiver differential code bias (rDCB). We modify the carrier-to-code leveling (CCL), a method commonly used to accomplish the first task, through assuming rDCB to be unlinked in time. Aside from the ionospheric observables, which are affected by, among others, the rDCB at one reference epoch, the Modified CCL (MCCL) can also provide the rDCB offsets with respect to the reference epoch as by-products. Two consequences arise. First, MCCL is capable of excluding the effects of time-varying rDCB from the ionospheric observables, which, in turn, improves the quality of ionospheric parameters of interest. Second, MCCL has significant potential as a means to detect between-epoch fluctuations experienced by rDCB of a single receiver.

Synergistic effect of hydrogen peroxide on polyploidization during the megakaryocytic differentiation of K562 leukemia cells by PMA

PubMed Central

Ojima, Yoshihiro; Duncan, Mark Thompson; Nurhayati, Retno Wahyu; Taya, Masahito; Miller, William Martin

2013-01-01

The human myelogenous cell line, K562 has been extensively used as a model for the study of megakaryocytic (MK) differentiation, which could be achieved by exposure to phorbol 12-myristate 13-acetate (PMA). In this study, real-time PCR analysis revealed that the expression of catalase (cat) was significantly repressed during MK differentiation of K562 cells induced by PMA. In addition, PMA increased the intracellular reactive oxygen species (ROS) concentration, suggesting that ROS was a key factor for PMA-induced differentiation. PMA-differentiated K562 cells were exposed to hydrogen peroxide (H2O2) to clarify the function of ROS during MK differentiation. Interestingly, the percentage of high-ploidy (DNA content >4N) cells with H2O2 was 34.8±2.3% at day 9, and was 70% larger than that without H2O2 (21.5±0.8%). Further, H2O2 addition during the first 3 days of PMA-induced MK differentiation had the greatest effect on polyploidization. In an effort to elucidate the mechanisms of enhanced polyploidization by H2O2, the BrdU assay clearly indicated that H2O2 suppressed the division of 4N cells into 2N cells, followed by the increased polyploidization of K562 cells. These findings suggest that the enhancement in polyploidization mediated by H2O2 is due to synergistic inhibition of cytokinesis with PMA. Although H2O2 did not increase ploidy during the MK differentiation of primary cells, we clearly observed that cat expression was repressed in both immature and mature primary MK cells, and that treatment with the antioxidant N-acetylcysteine effectively blocked and/or delayed the polyploidization of immature MK cells. Together, these findings suggest that MK cells are more sensitive to ROS levels during earlier stages of maturation. PMID:23770036

Differential effect of combined lipase deficiency (cld/cld) on human hepatic lipase and lipoprotein lipase secretion.

PubMed

Boedeker, J C; Doolittle, M H; White, A L

2001-11-01

Combined lipase deficiency (cld) is a recessively inherited disorder in mice associated with a deficiency of LPL and hepatic lipase (HL) activity. LPL is synthesized in cld tissues but is retained in the endoplasmic reticulum (ER), whereas mouse HL (mHL) is secreted but inactive. In this study we investigated the effect of cld on the secretion of human HL (hHL) protein mass and activity. Differentiated liver cell lines were derived from cld mice and their normal heterozygous (het) littermates by transformation of hepatocytes with SV40 large T antigen. After transient transfection with lipase expression constructs, secretion of hLPL activity from cld cells was only 12% of that from het cells. In contrast, the rate of secretion of hHL activity and protein mass per unit of expressed hHL mRNA was identical for the two cell lines. An intermediate effect was observed for mHL, with a 46% reduction in secretion of activity from cld cells. The ER glucosidase inhibitor, castanospermine, decreased secretion of both hLPL and hHL from het cells by approximately 70%, but by only approximately 45% from cld cells. This is consistent with data suggesting that cld may result from a reduced concentration of the ER chaperone calnexin. In conclusion, our results demonstrate a differential effect of cld on hLPL, mHL, and hHL secretion, suggesting differential requirements for activation and exit of the enzymes from the ER.

Effects of strontium-doped bioactive glass on the differentiation of cultured osteogenic cells.

PubMed

Isaac, J; Nohra, J; Lao, J; Jallot, E; Nedelec, J M; Berdal, A; Sautier, J M

2011-02-08

There is accumulating evidence that strontium-containing biomaterials have positive effects on bone tissue repair. We investigated the in vitro effect of a new Sr-doped bioactive glass manufactured by the sol-gel method on osteoblast viability and differentiation. Osteoblasts isolated from foetal mouse calvaria were cultured in the presence of bioactive glass particles; particles were undoped (B75) or Sr-doped with 1 wt.% (B75-Sr1) and 5 wt.% (B75-Sr5). Morphological analysis was carried out by contrast-phase microscopy and scanning electron microscopy (SEM). Cell viability was evaluated by the MTS assay at 24 h, 48 h and 72 h. At 24 h, day 6 and day 12, osteoblast differentiation was evaluated by assaying alkaline phosphatase (ALP) activity, osteocalcin (OC) secretion and gene expression of various bone markers, using Real-Time-PCR. Alizarin Red staining and ALP histoenzymatic localisation were performed on day 12. Microscopic observations and MTS showed an absence of cytotoxicity in the three investigated bioactive glasses. B75-Sr5 particles in cell cultures, in comparison with those of B75 and B75-Sr1, resulted in a significant up-regulation of Runx2, Osterix, Dlx5, collagen I, ALP, bone sialoprotein (BSP) and OC mRNA levels on day 12, which was associated with an increase of ALP activity on day 6 and OC secretion on day 12. In conclusion, osteoblast differentiation of foetal mouse calvarial cells was enhanced in the presence of bioactive glass particles containing 5 wt.% strontium. Thus, B75-Sr5 may represent a promising bone-grafting material for bone regeneration procedures.

An alternative approach for modeling strength differential effect in sheet metals with symmetric yield functions

NASA Astrophysics Data System (ADS)

Kurukuri, Srihari; Worswick, Michael J.

2013-12-01

An alternative approach is proposed to utilize symmetric yield functions for modeling the tension-compression asymmetry commonly observed in hcp materials. In this work, the strength differential (SD) effect is modeled by choosing separate symmetric plane stress yield functions (for example, Barlat Yld 2000-2d) for the tension i.e., in the first quadrant of principal stress space, and compression i.e., third quadrant of principal stress space. In the second and fourth quadrants, the yield locus is constructed by adopting interpolating functions between uniaxial tensile and compressive stress states. In this work, different interpolating functions are chosen and the predictive capability of each approach is discussed. The main advantage of this proposed approach is that the yield locus parameters are deterministic and relatively easy to identify when compared to the Cazacu family of yield functions commonly used for modeling SD effect observed in hcp materials.

Effects of naringin on the proliferation and osteogenic differentiation of human amniotic fluid-derived stem cells.

PubMed

Liu, Meimei; Li, Yan; Yang, Shang-Tian

2017-01-01

Human amniotic fluid-derived stem cells (hAFSCs) are a novel cell source for generating osteogenic cells to treat bone diseases. Effective induction of osteogenic differentiation from hAFSCs is critical to fulfil their therapeutic potential. In this study, naringin, the main active compound of Rhizoma drynariae (a Chinese herbal medicine), was used to stimulate the proliferation and osteogenic differentiation of hAFSCs. The results showed that naringin enhanced the proliferation and alkaline phosphatase activity (ALP) of hAFSCs in a dose-dependent manner in the range 1-100 µg/ml, while an inhibition effect was observed at 200 µg/ml. Consistently, the calcium content also increased with naringin concentration up to 100 µg/ml. The enhanced osteogenic differentiation of hAFSCs by naringin was further confirmed by the dose-dependent upregulation of marker genes, including osteopontin (OPN) and Collagen I from RT-PCR analysis. The increased osteoprotegerin (OPG) expression and minimal expression of receptor activator of nuclear factor-κB ligand (RANKL) suggested that naringin also inhibited osteoclastogenesis of hAFSCs. In addition, the gene expressions of bone morphogenetic protein 4 (BMP4), runt-related transcription factor 2 (RUNX2), β-catenin and Cyclin D1 also increased significantly, indicating that naringin promotes the osteogenesis of hAFSCs via the BMP and Wnt-β-catenin signalling pathways. These results suggested that naringin can be used to upregulate the osteogenic differentiation of hAFSCs, which could provide an attractive and promising treatment for bone disorders. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

Effect of TCEA3 on the differentiation of bovine skeletal muscle satellite cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Yue; Tong, Hui-Li; Li, Shu-Feng

Bovine muscle-derived satellite cells (MDSCs) are important for animal growth. In this study, the effect of transcription elongation factor A3 (TCEA3) on bovine MDSC differentiation was investigated. Western blotting, immunofluorescence assays, and cytoplasmic and nuclear protein isolation and purification techniques were used to determine the expression pattern and protein localization of TCEA3 in bovine MDSCs during in vitro differentiation. TCEA3 expression was upregulated using the CRISPR/Cas9 technique to study its effects on MDSC differentiation in vitro. TCEA3 expression gradually increased during the in vitro differentiation of bovine MDSCs and peaked on the 5th day of differentiation. TCEA3 was mainly localized in the cytoplasmmore » of bovine MDSCs, and its expression was not detected in the nucleus. The level of TCEA3 was relatively higher in myotubes at a higher degree of differentiation than during early differentiation. After transfection with a TCEA3-activating plasmid vector (TCEA3 overexpression) for 24 h, the myotube fusion rate, number of myotubes, and expression levels of the muscle differentiation-related loci myogenin (MYOG) and myosin heavy chain 3 (MYH3) increased significantly during the in vitro differentiation of bovine MDSCs. After transfection with a TCEA3-inhibiting plasmid vector for 24 h, the myotube fusion rate, number of myotubes, and expression levels of MYOG and MYH3 decreased significantly. Our results indicated, for the first time, that TCEA3 promotes the differentiation of bovine MDSCs and have implications for meat production and animal rearing. - Highlights: • Muscle-derived satellite cell differentiation is promoted by TCEA3. • TCEA3 protein was localized in the cytoplasm, but not nuclei of bovine MDSCs. • TCEA3 levels increased as myotube differentiation increased. • TCEA3 affected myotube fusion, myotube counts, and MYOG and MYH3 levels.« less

Effect of lactoferrin on osteogenic differentiation of human adipose stem cells.

PubMed

Ying, Xiaozhou; Cheng, Shaowen; Wang, Wei; Lin, Zhongqin; Chen, Qingyu; Zhang, Wei; Kou, Dongquan; Shen, Yue; Cheng, Xiaojie; Peng, Lei; Zi Xu, Hua; Zhu Lu, Chuan

2012-03-01

Many in vitro studies of the analysis of the lactoferrin (LF) effect on cells have been reported. However, no study has yet investigated the effect of LF on osteogenic differentiation of human adipose-derived stem cells (hADSCs). The aim of this study was to evaluate the effect of LF on osteogenic differentiation of human adipose stem cells. The hADSCs were cultured in an osteogenic medium with 0, 10, 50 and 100 μg/ml LF, respectively. hADSC proliferation was analysed by Cell Counting Kit-8 (CCK-8) assay, and cell osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity assay, von Kossa staining and real-time polymerase chain reaction (RT-PCR). Cell proliferation was significantly increased by LF in a dose-dependent manner from days 4 to 14. Cells cultured with 100 μg/ml LF presented a higher activity compared with the control. The deposition of calcium was increased after the addition of LF. The mRNA expression of type I collagen (COL-I), ALP, osteocalcin (OCN) and RUNX2 increased markedly as a result of LF treatment. We have shown for the first time that LF could promote the proliferation and osteogenic differentiation of hADSCs, which could be a promising approach for enhancing osteogenic capacity of cell-based construction in bone tissue engineering.

Chirality Differentiation by Diffusion in Chiral Nematic Liquid Crystals

NASA Astrophysics Data System (ADS)

Jiang, Jinghua; Yang, Deng-Ke

2017-01-01

Chirality is of great importance in the living world. It helps differentiate biochemical reactions such as those that take place during digestion. It may also help differentiate physical processes such as diffusion. Aiming to study the latter effect, we investigate the diffusion of guest chiral molecules in chiral nematic (cholesteric) liquid-crystal hosts. We discover that the diffusion dramatically depends on the handedness of the guest and host molecules and the chiral differentiation is greatly enhanced by the proper alignment of the liquid-crystal host. The diffusion of a guest chiral molecule in a chiral host with the same handedness is much faster than in a chiral host with opposite handedness. We also observe that the differentiation of chirality depends on the diffusion direction with respect to the twisting direction (helical axis). These results might be important in understanding effects of chirality on physical processes that take place in biological organisms. In addition, this effect could be utilized for enantiomer separation.

The Differential Effects of Preschool: Evidence from Virginia

ERIC Educational Resources Information Center

Huang, Francis L.; Invernizzi, Marcia A.; Drake, E. Allison

2012-01-01

This study investigated the differential and persistent effects of a state-funded pre-K program, the Virginia Preschool Initiative (VPI). We analyzed data from a cohort of over 60,000 students nested in approximately 1000 schools from the beginning of kindergarten to the end of first grade using two-level hierarchical logistic regression models.…

Enhanced proliferation and dopaminergic differentiation of ventral mesencephalic precursor cells by synergistic effect of FGF2 and reduced oxygen tension

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jensen, Pia; Department of Neurosurgery, University of Bern, CH-3010 Bern; Gramsbergen, Jan-Bert

Effective numerical expansion of dopaminergic precursors might overcome the limited availability of transplantable cells in replacement strategies for Parkinson's disease. Here we investigated the effect of fibroblast growth factor-2 (FGF2) and FGF8 on expansion and dopaminergic differentiation of rat embryonic ventral mesencephalic neuroblasts cultured at high (20%) and low (3%) oxygen tension. More cells incorporated bromodeoxyuridine in cultures expanded at low as compared to high oxygen tension, and after 6 days of differentiation there were significantly more neuronal cells in low than in high oxygen cultures. Low oxygen during FGF2-mediated expansion resulted also in a significant increase in tyrosine hydroxylase-immunoreactivemore » (TH-ir) dopaminergic neurons as compared to high oxygen tension, but no corresponding effect was observed for dopamine release into the culture medium. However, switching FGF2-expanded cultures from low to high oxygen tension during the last two days of differentiation significantly enhanced dopamine release and intracellular dopamine levels as compared to all other treatment groups. In addition, the short-term exposure to high oxygen enhanced in situ assessed TH enzyme activity, which may explain the elevated dopamine levels. Our findings demonstrate that modulation of oxygen tension is a recognizable factor for in vitro expansion and dopaminergic differentiation of rat embryonic midbrain precursor cells.« less

A Comparison of Two-Stage Approaches for Fitting Nonlinear Ordinary Differential Equation Models with Mixed Effects.

PubMed

Chow, Sy-Miin; Bendezú, Jason J; Cole, Pamela M; Ram, Nilam

2016-01-01

Several approaches exist for estimating the derivatives of observed data for model exploration purposes, including functional data analysis (FDA; Ramsay & Silverman, 2005 ), generalized local linear approximation (GLLA; Boker, Deboeck, Edler, & Peel, 2010 ), and generalized orthogonal local derivative approximation (GOLD; Deboeck, 2010 ). These derivative estimation procedures can be used in a two-stage process to fit mixed effects ordinary differential equation (ODE) models. While the performance and utility of these routines for estimating linear ODEs have been established, they have not yet been evaluated in the context of nonlinear ODEs with mixed effects. We compared properties of the GLLA and GOLD to an FDA-based two-stage approach denoted herein as functional ordinary differential equation with mixed effects (FODEmixed) in a Monte Carlo (MC) study using a nonlinear coupled oscillators model with mixed effects. Simulation results showed that overall, the FODEmixed outperformed both the GLLA and GOLD across all the embedding dimensions considered, but a novel use of a fourth-order GLLA approach combined with very high embedding dimensions yielded estimation results that almost paralleled those from the FODEmixed. We discuss the strengths and limitations of each approach and demonstrate how output from each stage of FODEmixed may be used to inform empirical modeling of young children's self-regulation.

The effects of viscoelastic polymer substrates on adult stem cell differentiation

NASA Astrophysics Data System (ADS)

Chang, Chungchueh; Fields, Adam; Ramek, Alex; Jurukovski, Vladimir; Simon, Marcia; Rafailovich, Miriam

2009-03-01

Dental Pulp Stem Cells (DPSCs) are known to differentiate in either bone, dentine, or nerve tissue by different environment signals. In this study, we have determined whether differentiation could only through modification of the substrate mechanics. Atomic Force Microscopy (AFM) on Shear Modulation Force Microscopy (SMFM) mode indicated that the spun-cast polybutadiene (PB) thin films could be used to provide different stiffness substrates by changing the thicknesses of thin films. DPSCs were then plated on these substrates and cultured in standard media. After 28 days incubation, Lasar Scanning Confocal Microscopy (LSCM) with mercury lamp indicated that the crystals were observed only on hard surfaces. The Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray analysis (EDX analysis) indicated that the crystals are calcium phosphates. The Glancing Incidence Diffraction (GID) was also used to determine the structure of crystals. These results indicate that DPSCs could be differentiated into osteoblasts by mechanical stimuli from substrate mechanics.

[Effect of Yiguan Decoction on differentiation of bone marrow mesenchymal stem cells into hepatocyte-like cells: an experimental research].

PubMed

Ping, Jian; Chen, Hong-Yun; Yang, Zhou; Yang, Cheng; Xu, Lie-Ming

2014-03-01

To observe the effect of Yiguan Decoction (YGD) on differentiation of bone marrow mesenchymal stem cells (BMSCs) into hepatocyte-like cells in vitro. Rat BMSCs were isolated using whole bone marrow adherent method. The properties of BMSCs were identified by analyzing the expression of surface cytokines by flow cytometry. The third passage cells were differentiated into fat cells to identify their features. BMSCs were incubated with hepatocyte growth factor (HGF) plus fibroblast growth factor 4 (FGF4) or YGD containing serum YGD for 21 days. The mRNA expression of alpha-fetoprotein (alphaAFP), albumin (Alb), and hepatocyte nuclear factor 4alpha (HNF4alpha) were detected by real time PCR. Expression of AFP and cytokeratin 18 (CK18) protein was detected by cell immunofluorescence. Glycogen synthesis was observed using periodic acid-Schiff stain (PAS). CK18, Wnt 3alpha, and alphacatenin protein expressions were detected by Western blot. High expression of CD90, CD29, and CD44, and low expression of CD34 and CD11b were observed in BMSCs isolated by whole bone mar- row adherent method, and numerous lipid droplets were observed in BMSCs using oil red O staining. Both YGD containing serum and growth factor stimulated the expression levels of Alb, AFP, HNF4alpha mRNA and CK18 protein. The down-regulated expression of Wnt 3alpha and beta-catenin could be detected at 21 days after induction. The synthesized glycogen granule could be seen. Down-regulated Wnt 3alpha and beta-catenin expression could also be observed. YGD could induce the differentiation of rat BMSCs into hepatocyte-like cells, which was related to down-regulating Wnt/beta-catenin signal pathway.

Cognate effects and cognitive control in patients with parallel and differential bilingual aphasia.

PubMed

Van der Linden, Lize; Verreyt, Nele; De Letter, Miet; Hemelsoet, Dimitri; Mariën, Peter; Santens, Patrick; Stevens, Michaël; Szmalec, Arnaud; Duyck, Wouter

2018-05-01

Until today, there is no satisfying explanation for why one language may recover worse than another in differential bilingual aphasia. One potential explanation that has been largely unexplored is that differential aphasia is the consequence of a loss of language control rather than a loss of linguistic representations. Language control is part of a general control mechanism that also manages non-linguistic cognitive control. If this system is impaired, patients with differential aphasia could still show bilingual language activation, but they may be unable to manage activation in non-target languages, so that performance in another language is hindered. To investigate whether a loss of cognitive control, rather than the loss of word representations in a particular language, might underlie differential aphasia symptoms. We compared the performance of seven bilinguals with differential and eight bilinguals with parallel aphasia with 19 control bilinguals in a lexical decision and a flanker task to assess bilingual language co-activation and non-linguistic control respectively. We found similar cognate effects in the three groups, indicating similar lexical processing across groups. Additionally, we found a larger non-linguistic control congruency effect only for the patients with differential aphasia. The present data indicate preserved language co-activation for patients with parallel as well as differential aphasia. Furthermore, the results suggest a general cognitive control dysfunction, specifically for differential aphasia. Taken together, the results of the current study provide further support for the hypothesis of impaired cognitive control abilities in patients with differential aphasia, which has both theoretical and practical implications. © 2018 Royal College of Speech and Language Therapists.

Effects of combined mechanical stimulation on the proliferation and differentiation of pre-osteoblasts

PubMed Central

Kang, Kyung Shin; Lee, Seung-Jae; Lee, Haksue; Moon, Wonkyu

2011-01-01

We observed how combined mechanical stimuli affect the proliferation and differentiation of pre-osteoblasts. For this research, a bioreactor system was developed that can simultaneously stimulate cells with cyclic strain and ultrasound, each of which is known to effectively stimulate bone tissue regeneration. MC3T3-E1 pre-osteoblasts were chosen for bone tissue engineering due to their osteoblast-like characteristics. 3-D scaffolds were fabricated with polycaprolactone and poly-L-lactic acid using the salt leaching method. The cells were stimulated by the bioreactor with cyclic strain and ultrasound. The bioreactor was set at a frequency of 1.0 Hz and 10% strain for cyclic strain and 1.0 MHz and 30 mW/cm2 for ultrasound. Three experimental groups (ultrasound, cyclic strain, and combined stimulation) and a control group were examined. Each group was stimulated for 20 min/day. Mechanical stimuli did not affect MC3T3-E1 cell proliferation significantly up to 10 days when measured with the cell counting kit-8. However, gene expression analysis of collagen type-I, osteocalcin, RUNX2, and osterix revealed that the combined mechanical stimulation accelerated the matrix maturation of MC3T3-E1 cells. These results indicate that the combined mechanical stimulation can enhance the differentiation of pre-osteoblasts more efficiently than simple stimuli, in spite of no effect on cell proliferation. PMID:21532314

Effect of low-magnitude, high-frequency vibration on osteogenic differentiation of rat mesenchymal stromal cells

PubMed Central

Lau, Esther; Lee, Whitaik David; Li, Jason; Xiao, Andrew; Davies, John E.; Wu, Qianhong; Wang, Liyun; You, Lidan

2011-01-01

Whole body vibration (WBV), consisting of a low-magnitude, high-frequency (LMHF) signal, has been found to be anabolic to bone in vivo, which may act through alteration of the lineage commitment of mesenchymal stromal cells (MSC). Here, we investigated the effect of LMHF vibration on rat bone marrow-derived MSCs (rMSCs) in an in vitro system. We subjected rMSCs to repeated (six) bouts of 1-hour vibration at 0.3g and 60 Hz in the presence of osteogenic induction medium. The osteogenic differentiation of rMSCs under the loaded and non-loaded conditions was assessed by examining cell proliferation, alkaline phosphatase (ALP) activity, mRNA expression of various osteoblast-associated markers (ALP, Runx2, osterix, collagen type I alpha 1, bone sialoprotein, osteopontin, and osteocalcin), as well as matrix mineralization. We observed that LMHF vibration did not enhance the osteogenic differentiation of rMSCs. Surprisingly, we found that the mRNA level of osterix, a transcription factor necessary for osteoblast formation, was decreased, and matrix mineralization was inhibited. Our findings suggest that LMHF vibration may exert its anabolic effects in vivo via mechanosensing of a cell type different from MSCs. PMID:21344497

Alternative outcome definitions and their effect on the performance of methods for observational outcome studies.

PubMed

Reich, Christian G; Ryan, Patrick B; Schuemie, Martijn J

2013-10-01

A systematic risk identification system has the potential to test marketed drugs for important Health Outcomes of Interest or HOI. For each HOI, multiple definitions are used in the literature, and some of them are validated for certain databases. However, little is known about the effect of different definitions on the ability of methods to estimate their association with medical products. Alternative definitions of HOI were studied for their effect on the performance of analytical methods in observational outcome studies. A set of alternative definitions for three HOI were defined based on literature review and clinical diagnosis guidelines: acute kidney injury, acute liver injury and acute myocardial infarction. The definitions varied by the choice of diagnostic codes and the inclusion of procedure codes and lab values. They were then used to empirically study an array of analytical methods with various analytical choices in four observational healthcare databases. The methods were executed against predefined drug-HOI pairs to generate an effect estimate and standard error for each pair. These test cases included positive controls (active ingredients with evidence to suspect a positive association with the outcome) and negative controls (active ingredients with no evidence to expect an effect on the outcome). Three different performance metrics where used: (i) Area Under the Receiver Operator Characteristics (ROC) curve (AUC) as a measure of a method's ability to distinguish between positive and negative test cases, (ii) Measure of bias by estimation of distribution of observed effect estimates for the negative test pairs where the true effect can be assumed to be one (no relative risk), and (iii) Minimal Detectable Relative Risk (MDRR) as a measure of whether there is sufficient power to generate effect estimates. In the three outcomes studied, different definitions of outcomes show comparable ability to differentiate true from false control cases (AUC) and a

Combined effects of dentin sialoprotein and bone morphogenetic protein-2 on differentiation in human cementoblasts.

PubMed

Lee, So-Youn; Auh, Q-Schick; Kang, Soo-Kyung; Kim, Hyung-Joon; Lee, Jung-Woo; Noh, Kwantae; Jang, Jun-Hyeog; Kim, Eun-Cheol

2014-07-01

The aim of this study is to determine the effects of the combination of recombinant human BMP-2 (rh-BMP-2) and dentin sialoprotein (rh-DSP) on growth and differentiation in human cementoblasts and determine the underlying signal transduction mechanism. Compared to treatment of cementoblasts with either rh-BMP-2 or rh-DSP alone, the combination of rh-BMP-2 and rh-DSP synergistically increased cell growth, ALP activity, nodule formation and expression of differentiation markers. The differentiation-promoting effect was also observed in periodontal ligament cells and an osteoblastic cell line. Likewise, combination of rh-DSP and rh-BMP-2 increased BMP-2 mRNA expression and Smad1/5/8 phosphorylation, which was blocked by the BMP antagonist noggin. The expression levels of α2β1 integrin and RhoA, as well as the phosphorylation status of FAK and Akt, were increased by the combination of rh-BMP-2 and rh-DSP in a time-dependent manner. In addition, rh-BMP-2 and rh-DSP enhanced expression of Wnt ligands, β-catenin activation and GSK-3β phosphorylation, all of which were inhibited by the Wnt receptor antagonist DKK1. Furthermore, treatment with rh-DSP plus rh-BMP-2 resulted in phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 and also induced the nuclear translocation of the NF-κB p65 subunit, which was blocked by noggin. This study demonstrates for the first time that rh-DSP and rh-BMP-2 act synergistically, enhancing each other's ability to stimulate cementoblastic cell growth and differentiation in vitro via autocrine BMP, integrin, Wnt/β-catenin, MAP kinase and NF-κB pathways. These results support the therapeutic potential of a combination strategy for aiding periodontal regeneration.

Effects and mechanisms of melatonin on the proliferation and neural differentiation of PC12 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Yumei; Zhang, Ziqiang; Lv, Qiongxia

Melatonin, a lipophilic molecule that is mainly synthesized in the pineal gland, performs various neuroprotective functions. However, the detailed role and mechanisms of promoting neuronal differentiation remains limited. This study demonstrated that 10 μM melatonin led to significant increases in the proliferation and neurite outgrowth of PC12 cells. Increased expression of microtubule-associated protein 2 (MAP2, a neuron-specific protein) was also observed. However, luzindole (melatonin receptor antagonist) and PD98059 (MEK inhibitor) attenuated these increases. LY294002 (AKT inhibitor) inhibited melatonin-mediated proliferation in PC12 cells and did not affect melatonin-induced neural differentiation. The expression of p-ERK1/2/ERK1/2 was increased by melatonin treatment for 14 days in PC12 cells,more » whereas luzindole or PD98059 reduced the melatonin-induced increase. These results suggest that the activation of both the MEK/ERK and PI3K/AKT signaling pathways could potentially contribute to melatonin-mediated proliferation, but that only the MEK/ERK pathway participates in the melatonin-induced neural differentiation of PC12 cells. Altogether, our study demonstrates for the first time that melatonin may exert a positive effect on neural differentiation via melatonin receptor signalling and that the MEK/ERK1/2 signalling may act down stream from the melatonin pathway. - Highlights: • Melatonin improves the proliferation of PC12 cells. • Melatonin induces neural differentiation of PC12 cells. • Melatonin-mediated proliferation in PC12 cells relies on the ERK and AKT pathways. • Activation of ERK is essential for melatonin-induced neural differentiation of PC12.« less

Clustering gene expression data based on predicted differential effects of GV interaction.

PubMed

Pan, Hai-Yan; Zhu, Jun; Han, Dan-Fu

2005-02-01

Microarray has become a popular biotechnology in biological and medical research. However, systematic and stochastic variabilities in microarray data are expected and unavoidable, resulting in the problem that the raw measurements have inherent "noise" within microarray experiments. Currently, logarithmic ratios are usually analyzed by various clustering methods directly, which may introduce bias interpretation in identifying groups of genes or samples. In this paper, a statistical method based on mixed model approaches was proposed for microarray data cluster analysis. The underlying rationale of this method is to partition the observed total gene expression level into various variations caused by different factors using an ANOVA model, and to predict the differential effects of GV (gene by variety) interaction using the adjusted unbiased prediction (AUP) method. The predicted GV interaction effects can then be used as the inputs of cluster analysis. We illustrated the application of our method with a gene expression dataset and elucidated the utility of our approach using an external validation.

Effects of heat shock on neuroblastoma (N1E 115) cell proliferation and differentiation.

PubMed

Stoklosinski, A; Kruse, H; Richter-Landsberg, C; Rensing, L

1992-05-01

Heat shock (44 degrees C) applied for only 15 min induced the development of neurites in neuroblastoma cells 3-6 days later. During the first day after heat shock a transient increase in the rate of cytokinesis together with a synchronizing effect was observed, which led to waves of cytokinesis 14.5 h apart. Individual cell cycles were determined and showed a lengthening in the minimal cell cycle duration and a decrease in the cell cycle variance after shock. Two to 3 days after heat shock the proliferation rate decreased and then recovered. During the 6 days after heat shock, total protein synthesis was lower compared to the untreated cultures. The synthesis of heat shock proteins (100, 90, 84, 70, 68 kDa and some of lower MW) reached a maximum 6 h after heat shock. Parallel changes in the phosphorylation state of proteins were observed in an in vitro assay. Four proteins (100, 89, 67, and 15 kDa) increased and two proteins (97, 73 kDa) decreased their phosphorylation state significantly. Six days after heat shock two proteins (89, 55 kDa) increased their phosphorylation state; the 55-kDa phosphoprotein was identified as tubulin. The effect of heat shock on the intracellular calcium level was determined by measuring Fura 2 fluorescence. Six hours after shock, the Ca2+ level increased to a maximum (about three times the control value) and then dropped during the following days below the control values. We conclude from these results that a decrease in the calcium level may be causally involved in the differentiation process. The calcium effect is probably mediated by changes in the activity of different kinases. This assumption is compatible with the results of experiments with cyclic nucleotides when 10(-5) M cAMP and cGMP were added to in vitro assays of protein phosphorylation. They had different stimulating effects in heat-shocked, differentiating, and growing (control) cells.

Differentiation: Lessons from Master Teachers

ERIC Educational Resources Information Center

Carolan, Jennifer; Guinn, Abigail

2007-01-01

Carolan and Guinn assert that differentiated instruction helps diversity thrive. Observing how experienced teachers practice differentiation in real-life situations helps teachers who are reluctant to try such strategies take the plunge. The authors draw on two observational studies they conducted of five expert teachers in a high-performing,…

Effects of Angular Variation on Split D Differential Eddy Current Probe Response (Postprint)

DTIC Science & Technology

2016-02-10

AFRL-RX-WP-JA-2016-0327 EFFECTS OF ANGULAR VARIATION ON SPLIT D DIFFERENTIAL EDDY CURRENT PROBE RESPONSE (POSTPRINT) Ryan D...March 2014 – 22 September 2015 4. TITLE AND SUBTITLE EFFECTS OF ANGULAR VARIATION ON SPLIT D DIFFERENTIAL EDDY CURRENT PROBE RESPONSE (POSTPRINT...last few years have seen increased levels of complexity added to push the state-of-the-art modeling software used in eddy current NDE today. The added

mTOR complexes differentially orchestrates eosinophil development in allergy.

PubMed

Zhu, Chen; Xia, Lixia; Li, Fei; Zhou, Lingren; Weng, Qingyu; Li, Zhouyang; Wu, Yinfang; Mao, Yuanyuan; Zhang, Chao; Wu, Yanping; Li, Miao; Ying, Songmin; Chen, Zhihua; Shen, Huahao; Li, Wen

2018-05-02

Eosinophil infiltration is considered a hallmark in allergic airway inflammation, and the blockade of eosinophil differentiation may be an effective approach for treating eosinophil-related disorders. Mammalian target of rapamycin (mTOR) is a vital modulator in cell growth control and related diseases, and we have recently demonstrated that rapamycin can suppress eosinophil differentiation in allergic airway inflammation. Considering its critical role in haematopoiesis, we further investigated the role of mTOR in eosinophil differentiation in the context of asthmatic pathogenesis. Intriguingly, the inhibition of mTOR, either by genetic deletion or by another pharmacological inhibitor torin-1, accelerated the eosinophil development in the presence of IL-5. However, this was not observed to have any considerable effect on eosinophil apoptosis. The effect of mTOR in eosinophil differentiation was mediated by Erk signalling. Moreover, myeloid specific knockout of mTOR or Rheb further augmented allergic airway inflammation in mice after allergen exposure. Ablation of mTOR in myeloid cells also resulted in an increased number of eosinophil lineage-committed progenitors (Eops) in allergic mice. Collectively, our data uncovered the differential effects of mTOR in the regulation of eosinophil development, likely due to the distinct functions of mTOR complex 1 or 2, which thus exerts a pivotal implication in eosinophil-associated diseases.

MCNP modelling of the wall effects observed in tissue-equivalent proportional counters.

PubMed

Hoff, J L; Townsend, L W

2002-01-01

Tissue-equivalent proportional counters (TEPCs) utilise tissue-equivalent materials to depict homogeneous microscopic volumes of human tissue. Although both the walls and gas simulate the same medium, they respond to radiation differently. Density differences between the two materials cause distortions, or wall effects, in measurements, with the most dominant effect caused by delta rays. This study uses a Monte Carlo transport code, MCNP, to simulate the transport of secondary electrons within a TEPC. The Rudd model, a singly differential cross section with no dependence on electron direction, is used to describe the energy spectrum obtained by the impact of two iron beams on water. Based on the models used in this study, a wall-less TEPC had a higher lineal energy (keV.micron-1) as a function of impact parameter than a solid-wall TEPC for the iron beams under consideration. An important conclusion of this study is that MCNP has the ability to model the wall effects observed in TEPCs.

The effect of low-frequency electromagnetic field on human bone marrow stem/progenitor cell differentiation

PubMed Central

Ross, Christina L.; Siriwardane, Mevan; Almeida-Porada, Graça; Porada, Christopher D.; Brink, Peter; Christ, George J.; Harrison, Benjamin S.

2015-01-01

Human bone marrow stromal cells (hBMSCs, also known as bone marrow-derived mesenchymal stem cells) are a population of progenitor cells that contain a subset of skeletal stem cells (hSSCs), able to recreate cartilage, bone, stroma that supports hematopoiesis and marrow adipocytes. As such, they have become an important resource in developing strategies for regenerative medicine and tissue engineering due to their self-renewal and differentiation capabilities. The differentiation of SSCs/BMSCs is dependent on exposure to biophysical and biochemical stimuli that favor early and rapid activation of the in vivo tissue repair process. Exposure to exogenous stimuli such as an electromagnetic field (EMF) can promote differentiation of SSCs/BMSCs via ion dynamics and small signaling molecules. The plasma membrane is often considered to be the main target for EMF signals and most results point to an effect on the rate of ion or ligand binding due to a receptor site acting as a modulator of signaling cascades. Ion fluxes are closely involved in differentiation control as stem cells move and grow in specific directions to form tissues and organs. EMF affects numerous biological functions such as gene expression, cell fate, and cell differentiation, but will only induce these effects within a certain range of low frequencies as well as low amplitudes. EMF has been reported to be effective in the enhancement of osteogenesis and chondrogenesis of hSSCs/BMSCs with no documented negative effects. Studies show specific EMF frequencies enhance hSSC/BMSC adherence, proliferation, differentiation, and viability, all of which play a key role in the use of hSSCs/BMSCs for tissue engineering. While many EMF studies report significant enhancement of the differentiation process, results differ depending on the experimental and environmental conditions. Here we review how specific EMF parameters (frequency, intensity, and time of exposure) significantly regulate hSSC/BMSC differentiation in

Effect of essential amino acids on enteroids: Methionine deprivation suppresses proliferation and affects differentiation in enteroid stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saito, Yuki; Iwatsuki, Ken; Hanyu, Hikaru

We investigated the effects of essential amino acids on intestinal stem cell proliferation and differentiation using murine small intestinal organoids (enteroids) from the jejunum. By selectively removing individual essential amino acids from culture medium, we found that 24 h of methionine (Met) deprivation markedly suppressed cell proliferation in enteroids. This effect was rescued when enteroids cultured in Met deprivation media for 12 h were transferred to complete medium, suggesting that Met plays an important role in enteroid cell proliferation. In addition, mRNA levels of the stem cell marker leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) decreased in enteroids grown in Met deprivationmore » conditions. Consistent with this observation, Met deprivation also attenuated Lgr5-EGFP fluorescence intensity in enteroids. In contrast, Met deprivation enhanced mRNA levels of the enteroendocrine cell marker chromogranin A (ChgA) and markers of K cells, enterochromaffin cells, goblet cells, and Paneth cells. Immunofluorescence experiments demonstrated that Met deprivation led to an increase in the number of ChgA-positive cells. These results suggest that Met deprivation suppresses stem cell proliferation, thereby promoting differentiation. In conclusion, Met is an important nutrient in the maintenance of intestinal stem cells and Met deprivation potentially affects cell differentiation. - Highlights: • Met influences the proliferation of enteroids. • Met plays a crucial role in the maintenance of stem cells. • Met deprivation potentially promotes differentiation into secretory cells.« less

Differential effects of RNAi treatments on field populations of the western corn rootworm.

PubMed

Chu, Chia-Ching; Sun, Weilin; Spencer, Joseph L; Pittendrigh, Barry R; Seufferheld, Manfredo J

2014-03-01

RNA interference (RNAi) mediated crop protection against insect pests is a technology that is greatly anticipated by the academic and industrial pest control communities. Prior to commercialization, factors influencing the potential for evolution of insect resistance to RNAi should be evaluated. While mutations in genes encoding the RNAi machinery or the sequences targeted for interference may serve as a prominent mechanism of resistance evolution, differential effects of RNAi on target pests may also facilitate such evolution. However, to date, little is known about how variation of field insect populations could influence the effectiveness of RNAi treatments. To approach this question, we evaluated the effects of RNAi treatments on adults of three western corn rootworm (WCR; Diabrotica virgifera virgifera LeConte) populations exhibiting different levels of gut cysteine protease activity, tolerance of soybean herbivory, and immune gene expression; two populations were collected from crop rotation-resistant (RR) problem areas and one from a location where RR was not observed (wild type; WT). Our results demonstrated that RNAi targeting DvRS5 (a highly expressed cysteine protease gene) reduced gut cysteine protease activity in all three WCR populations. However, the proportion of the cysteine protease activity that was inhibited varied across populations. When WCR adults were treated with double-stranded RNA of an immune gene att1, different changes in survival among WT and RR populations on soybean diets occurred. Notably, for both genes, the sequences targeted for RNAi were the same across all populations examined. These findings indicate that the effectiveness of RNAi treatments could vary among field populations depending on their physiological and genetic backgrounds and that the consistency of an RNAi trait's effectiveness on phenotypically different populations should be considered or tested prior to wide deployment. Also, genes that are potentially subjected

Mitochondrial and lipogenic effects of vitamin D on differentiating and proliferating human keratinocytes.

PubMed

Consiglio, Marco; Viano, Marta; Casarin, Stefania; Castagnoli, Carlotta; Pescarmona, Gianpiero; Silvagno, Francesca

2015-10-01

Even in cells that are resistant to the differentiating effects of vitamin D, the activated vitamin D receptor (VDR) can downregulate the mitochondrial respiratory chain and sustain cell growth through enhancing the activity of biosynthetic pathways. The aim of this study was to investigate whether vitamin D is effective also in modulating mitochondria and biosynthetic metabolism of differentiating cells. We compared the effect of vitamin D on two cellular models: the primary human keratinocytes, differentiating and sensitive to the genomic action of VDR, and the human keratinocyte cell line HaCaT, characterized by a rapid growth and resistance to vitamin D. We analysed the nuclear translocation and features of VDR, the effects of vitamin D on mitochondrial transcription and the consequences on lipid biosynthetic fate. We found that the negative modulation of respiratory chain is a general mechanism of action of vitamin D, but at high doses, the HaCaT cells became resistant to mitochondrial effects by upregulating the catabolic enzyme CYP24 hydroxylase. In differentiating keratinocytes, vitamin D treatment promoted intracellular lipid deposition, likewise the inhibitor of respiratory chain stigmatellin, whereas in proliferating HaCaT, this biosynthetic pathway was not inducible by the hormone. By linking the results on respiratory chain and lipid accumulation, we conclude that vitamin D, by suppressing respiratory chain transcription in all keratinocytes, is able to support both the proliferation and the specialized metabolism of differentiating cells. Through mitochondrial control, vitamin D can have an essential role in all the metabolic phenotypes occurring in healthy and diseased skin. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Reversible effects of oxygen partial pressure on genes associated with placental angiogenesis and differentiation in primary-term cytotrophoblast cell culture.

PubMed

Debiève, F; Depoix, C; Gruson, D; Hubinont, C

2013-09-01

Timely regulated changes in oxygen partial pressure are important for placental formation. Disturbances could be responsible for pregnancy-related diseases like preeclampsia and intrauterine growth restriction. We aimed to (i) determine the effect of oxygen partial pressure on cytotrophoblast differentiation; (ii) measure mRNA expression and protein secretion from genes associated with placental angiogenesis; and (iii) determine the reversibility of these effects at different oxygen partial pressures. Term cytotrophoblasts were incubated at 21% and 2.5% O2 for 96 hr, or were switched between the two oxygen concentrations after 48 hr. Real-time PCR and enzyme-linked immunosorbent assays (ELISAs) were used to evaluate cell fusion and differentiation, measuring transcript levels for those genes involved in cell fusion and placental angiogenesis, including VEGF, PlGF, VEGFR1, sVEGFR1, sENG, INHA, and GCM1. Cytotrophoblasts underwent fusion and differentiation in 2.5% O2 . PlGF expression was inhibited while sVEGFR1 expression increased. VEGF and sENG mRNA expressions increased in 2.5% compared to 21% O2 , but no protein was detected in the cell supernatants. Finally, GCM1 mRNA expression increased during trophoblast differentiation at 21% O2 , but was inhibited at 2.5% O2 . These mRNA expression effects were reversed by returning the cells to 21% O2 . Thus, low-oxygen partial pressure does not inhibit term-cytotrophoblast cell fusion and differentiation in vitro. Lowering the oxygen partial pressure from 21% to 2.5% caused normal-term trophoblasts to reversibly modify their expression of genes associated with placental angiogenesis. This suggests that modifications observed in pregnancy diseases such as preeclampsia or growth retardation are probably due to an extrinsic effect on trophoblasts. Copyright © 2013 Wiley Periodicals, Inc.

Synergistic effect of hydrogen peroxide on polyploidization during the megakaryocytic differentiation of K562 leukemia cells by PMA.

PubMed

Ojima, Yoshihiro; Duncan, Mark Thompson; Nurhayati, Retno Wahyu; Taya, Masahito; Miller, William Martin

2013-08-15

The human myelogenous cell line, K562 has been extensively used as a model for the study of megakaryocytic (MK) differentiation, which could be achieved by exposure to phorbol 12-myristate 13-acetate (PMA). In this study, real-time PCR analysis revealed that the expression of catalase (cat) was significantly repressed during MK differentiation of K562 cells induced by PMA. In addition, PMA increased the intracellular reactive oxygen species (ROS) concentration, suggesting that ROS was a key factor for PMA-induced differentiation. PMA-differentiated K562 cells were exposed to hydrogen peroxide (H2O2) to clarify the function of ROS during MK differentiation. Interestingly, the percentage of high-ploidy (DNA content >4N) cells with H2O2 was 34.8±2.3% at day 9, and was 70% larger than that without H2O2 (21.5±0.8%). Further, H2O2 addition during the first 3 days of PMA-induced MK differentiation had the greatest effect on polyploidization. In an effort to elucidate the mechanisms of enhanced polyploidization by H2O2, the BrdU assay clearly indicated that H2O2 suppressed the division of 4N cells into 2N cells, followed by the increased polyploidization of K562 cells. These findings suggest that the enhancement in polyploidization mediated by H2O2 is due to synergistic inhibition of cytokinesis with PMA. Although H2O2 did not increase ploidy during the MK differentiation of primary cells, we clearly observed that cat expression was repressed in both immature and mature primary MK cells, and that treatment with the antioxidant N-acetylcysteine effectively blocked and/or delayed the polyploidization of immature MK cells. Together, these findings suggest that MK cells are more sensitive to ROS levels during earlier stages of maturation. Copyright © 2013 Elsevier Inc. All rights reserved.

The Effects of Low-Dose Bisphenol A and Bisphenol F on Neural Differentiation of a Fetal Brain-Derived Neural Progenitor Cell Line.

PubMed

Fujiwara, Yuki; Miyazaki, Wataru; Koibuchi, Noriyuki; Katoh, Takahiko

2018-01-01

Environmental chemicals are known to disrupt the endocrine system in humans and to have adverse effects on several organs including the developing brain. Recent studies indicate that exposure to environmental chemicals during gestation can interfere with neuronal differentiation, subsequently affecting normal brain development in newborns. Xenoestrogen, bisphenol A (BPA), which is widely used in plastic products, is one such chemical. Adverse effects of exposure to BPA during pre- and postnatal periods include the disruption of brain function. However, the effect of BPA on neural differentiation remains unclear. In this study, we explored the effects of BPA or bisphenol F (BPF), an alternative compound for BPA, on neural differentiation using ReNcell, a human fetus-derived neural progenitor cell line. Maintenance in growth factor-free medium initiated the differentiation of ReNcell to neuronal cells including neurons, astrocytes, and oligodendrocytes. We exposed the cells to BPA or BPF for 3 days from the period of initiation and performed real-time PCR for neural markers such as β III-tubulin and glial fibrillary acidic protein (GFAP), and Olig2. The β III-tubulin mRNA level decreased in response to BPA, but not BPF, exposure. We also observed that the number of β III-tubulin-positive cells in the BPA-exposed group was less than that of the control group. On the other hand, there were no changes in the MAP2 mRNA level. These results indicate that BPA disrupts neural differentiation in human-derived neural progenitor cells, potentially disrupting brain development.

Effects of parabens on adipocyte differentiation.

PubMed

Hu, Pan; Chen, Xin; Whitener, Rick J; Boder, Eric T; Jones, Jeremy O; Porollo, Aleksey; Chen, Jiangang; Zhao, Ling

2013-01-01

Parabens are a group of alkyl esters of p-hydroxybenzoic acid that include methylparaben, ethylparaben, propylparaben, butylparaben, and benzylparaben. Paraben esters and their salts are widely used as preservatives in cosmetics, toiletries, food, and pharmaceuticals. Humans are exposed to parabens through the use of such products from dermal contact, ingestion, and inhalation. However, research on the effects of parabens on health is limited, and the effects of parabens on adipogenesis have not been systematically studied. Here, we report that (1) parabens promote adipogenesis (or adipocyte differentiation) in murine 3T3-L1 cells, as revealed by adipocyte morphology, lipid accumulation, and mRNA expression of adipocyte-specific markers; (2) the adipogenic potency of parabens is increased with increasing length of the linear alkyl chain in the following potency ranking order: methyl- < ethyl- < propyl- < butylparaben. The extension of the linear alkyl chain with an aromatic ring in benzylparaben further augments the adipogenic ability, whereas 4-hydroxybenzoic acid, the common metabolite of all parabens, and the structurally related benzoic acid (without the OH group) are inactive in promoting 3T3-L1 adipocyte differentiation; (3) parabens activate glucocorticoid receptor and/or peroxisome proliferator-activated receptor γ in 3T3-L1 preadipocytes; however, no direct binding to, or modulation of, the ligand binding domain of the glucocorticoid receptor by parabens was detected by glucocorticoid receptor competitor assays; and lastly, (4) parabens, butyl- and benzylparaben in particular, also promote adipose conversion of human adipose-derived multipotent stromal cells. Our results suggest that parabens may contribute to obesity epidemic, and the role of parabens in adipogenesis in vivo needs to be examined further.

Effect of deformation path on microstructure, microhardness and texture evolution of interstitial free steel fabricated by differential speed rolling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamad, Kotiba; Chung, Bong Kwon; Ko, Young Gun, E-mail: younggun@ynu.ac.kr

2014-08-15

This paper reports the effect of the deformation path on the microstructure, microhardness, and texture evolution of interstitial free (IF) steel processed by differential speed rolling (DSR) method. For this purpose, total height reductions of 50% and 75% were imposed on the samples by a series of differential speed rolling operations with various height reductions per pass (deformation levels) ranging from 10 to 50% under a fixed roll speed ratio of 1:4 for the upper and lower rolls, respectively. Microstructural observations using transmission electron microscopy and electron backscattered diffraction measurements showed that the samples rolled at deformation level of 50%more » had the finest mean grain size (∼ 0.5 μm) compared to the other counterparts; also the samples rolled at deformation level of 50% showed a more uniform microstructure. Based on the microhardness measurements along the thickness direction of the deformed samples, gradual evolution of the microhardness value and its homogeneity was observed with the increase of the deformation level per pass. Texture analysis showed that, as the deformation level per pass increased, the fraction of alpha fiber and gamma fiber in the deformed samples increased. The textures obtained by the differential speed rolling process under the lubricated condition would be equivalent to those obtained by the conventional rolling. - Highlights: • Effect of DSR deformation path on microstructure of IF steel is significant. • IF steel rolled at deformation level of 50% has the ultrafine grains of ∼ 0.5 μm. • Rolling texture components are pronounced with increasing deformation level.« less

Agreement among Classroom Observers of Children's Stylistic Learning Behaviors.

ERIC Educational Resources Information Center

Buchanan, Helen Hamlet; McDermott, Paul A.; Schaefer, Barbara A.

1998-01-01

Investigates the interobserver agreement of the Learning Behavior Scale (LBS) by educators (n=16) observing students in special-education classes (n=72). No significant observer effect was found. Moreover, the LBS produced comparable levels of differential learning styles for assessments of individual children. (Author/MKA)

Differential Susceptibility to the Effects of Child Temperament on Maternal Warmth and Responsiveness

ERIC Educational Resources Information Center

Lee, Eunju J.

2013-01-01

A child's difficult temperament can elicit negative parenting and inhibit positive parenting behavior. However, mothers appear to be differentially susceptible to child temperament. The author examined the differential susceptibility to the effects of a child's temperament on the mother-child interaction style (i.e., maternal warmth and…

A Comparison of Two-Stage Approaches for Fitting Nonlinear Ordinary Differential Equation (ODE) Models with Mixed Effects

PubMed Central

Chow, Sy-Miin; Bendezú, Jason J.; Cole, Pamela M.; Ram, Nilam

2016-01-01

Several approaches currently exist for estimating the derivatives of observed data for model exploration purposes, including functional data analysis (FDA), generalized local linear approximation (GLLA), and generalized orthogonal local derivative approximation (GOLD). These derivative estimation procedures can be used in a two-stage process to fit mixed effects ordinary differential equation (ODE) models. While the performance and utility of these routines for estimating linear ODEs have been established, they have not yet been evaluated in the context of nonlinear ODEs with mixed effects. We compared properties of the GLLA and GOLD to an FDA-based two-stage approach denoted herein as functional ordinary differential equation with mixed effects (FODEmixed) in a Monte Carlo study using a nonlinear coupled oscillators model with mixed effects. Simulation results showed that overall, the FODEmixed outperformed both the GLLA and GOLD across all the embedding dimensions considered, but a novel use of a fourth-order GLLA approach combined with very high embedding dimensions yielded estimation results that almost paralleled those from the FODEmixed. We discuss the strengths and limitations of each approach and demonstrate how output from each stage of FODEmixed may be used to inform empirical modeling of young children’s self-regulation. PMID:27391255

Neurotrophic effects of growth/differentiation factor 5 in a neuronal cell line.

PubMed

Toulouse, André; Collins, Grace C; Sullivan, Aideen M

2012-04-01

The neurotrophin growth/differentiation factor 5 (GDF5) is studied as a potential therapeutic agent for Parkinson's disease as it is believed to play a role in the development and maintenance of the nigrostriatal system. Progress in understanding the effects of GDF5 on dopaminergic neurones has been hindered by the use of mixed cell populations derived from primary cultures or in vivo experiments, making it difficult to differentiate between direct and indirect effects of GDF5 treatment on neurones. In an attempt to establish an useful model to study the direct neuronal influence of GDF5, we have characterised the effects of GDF5 on a human neuronal cell line, SH-SY5Y. Our results show that GDF5 has the capability to promote neuronal but not dopaminergic differentiation. We also show that it promotes neuronal survival in vitro following a 6-hydroxydopamine insult. Our results show that application of GDF5 to SH-SY5Y cultures induces the SMAD pathway which could potentially be implicated in the intracellular transmission of GDF5's neurotrophic effects. Overall, our study shows that the SH-SY5Y neuroblastoma cell line provides an excellent neuronal model to study the neurotrophic effects of GDF5.

Negative differential resistance observed from vertical p+-n+ junction device with two-dimensional black phosphorous

NASA Astrophysics Data System (ADS)

Lee, Daeyeong; Jang, Young Dae; Kweon, Jaehwan; Ryu, Jungjin; Hwang, Euyheon; Yoo, Won Jong; Samsung-SKKU Graphene/2D Center (SSGC) Collaboration

A vertical p+-n+ homojunction was fabricated by using black phosphorus (BP) as a van der Waals two-dimensional (2D) material. The top and bottom layers of the materials were doped by chemical dopants of gold chloride (AuCl3) for p-type doping and benzyl viologen (BV) for n-type doping. The negative differential resistance (NDR) effect was clearly observed from the output curves of the fabricated BP vertical devices. The thickness range of the 2D material showing NDR and the peak to valley current ratio of NDR are found to be strongly dependent on doping condition, gate voltage, and BP's degradation level. Furthermore, the carrier transport of the p+-n+ junction was simulated by using density functional theory (DFT) and non-equilibrium Green's function (NEGF). Both the experimental and simulation results confirmed that the NDR is attributed to the band-to-band tunneling (BTBT) across the 2D BP p+-n+ junction, and further quantitative details on the carrier transport in the vertical p+-n+ junction devices were explored, according to the analyses of the measured transfer curves and the DFT simulation results. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (2013R1A2A2A01015516).

ORCHIDS: an observational randomized controlled trial on childhood differential susceptibility.

PubMed

Chhangur, Rabia R; Weeland, Joyce; Overbeek, Geertjan; Matthys, Walterchj; Orobio de Castro, Bram

2012-10-29

A central tenet in developmental psychopathology is that childhood rearing experiences have a major impact on children's development. Recently, candidate genes have been identified that may cause children to be differentially susceptible to these experiences (i.e., susceptibility genes). However, our understanding of the differential impact of parenting is limited at best. Specifically, more experimental research is needed. The ORCHIDS study will investigate gene-(gene-)environment interactions to obtain more insight into a) moderating effects of polymorphisms on the link between parenting and child behavior, and b) behavioral mechanisms that underlie these gene-(gene-)environment interactions in an experimental design. The ORCHIDS study is a randomized controlled trial, in which the environment will be manipulated with an intervention (i.e., Incredible Years parent training). In a screening, families with children aged 4-8 who show mild to (sub)clinical behavior problems will be targeted through community records via two Dutch regional healthcare organizations. Assessments in both the intervention and control condition will be conducted at baseline (i.e., pretest), after 6 months (i.e., posttest), and after 10 months (i.e., follow-up). This study protocol describes the design of a randomized controlled trial that investigates gene-(gene-)environment interactions in the development of child behavior. Two hypotheses will be tested. First, we expect that children in the intervention condition who carry one or more susceptibility genes will show significantly lower levels of problem behavior and higher levels of prosocial behavior after their parent(s) received the Incredible Years training, compared to children without these genes, or children in the control group. Second, we expect that children carrying one or more susceptibility genes will show a heightened sensitivity to changes in parenting behaviors, and will manifest higher emotional synchronization in dyadic

The Differential Effect of Sustained Operations on Psychomotor Skills of Helicopter Pilots.

PubMed

McMahon, Terry W; Newman, David G

2018-06-01

Flying a helicopter is a complex psychomotor skill requiring constant control inputs from pilots. A deterioration in psychomotor performance of a helicopter pilot may be detrimental to operational safety. The aim of this study was to test the hypothesis that psychomotor performance deteriorates over time during sustained operations and that the effect is more pronounced in the feet than the hands. The subjects were helicopter pilots conducting sustained multicrew offshore flight operations in a demanding environment. The remote flight operations involved constant workload in hot environmental conditions with complex operational tasking. Over a period of 6 d 10 helicopter pilots were tested. At the completion of daily flying duties, a helicopter-specific screen-based compensatory tracking task measuring tracking accuracy (over a 5-min period) tested both hands and feet. Data were compared over time and tested for statistical significance for both deterioration and differential effect. A statistically significant deterioration of psychomotor performance was evident in the pilots over time for both hands and feet. There was also a statistically significant differential effect between the hands and the feet in terms of tracking accuracy. The hands recorded a 22.6% decrease in tracking accuracy, while the feet recorded a 39.9% decrease in tracking accuracy. The differential effect may be due to prioritization of limb movement by the motor cortex due to factors such as workload-induced cognitive fatigue. This may result in a greater reduction in performance in the feet than the hands, posing a significant risk to operational safety.McMahon TW, Newman DG. The differential effect of sustained operations on psychomotor skills of helicopter pilots. Aerosp Med Hum Perform. 2018; 89(6):496-502.

Effects of a History of Differential Reinforcement on Preference for Choice

PubMed Central

Karsina, Allen; Thompson, Rachel H; Rodriguez, Nicole M

2011-01-01

The effects of a history of differential reinforcement for selecting a free-choice versus a restricted-choice stimulus arrangement on the subsequent responding of 7 undergraduates in a computer-based game of chance were examined using a concurrent-chains arrangement and a multiple-baseline-across-participants design. In the free-choice arrangement, participants selected three numbers, in any order, from an array of eight numbers presented on the computer screen. In the restricted-choice arrangement, participants selected the order of three numbers preselected from the array of eight by a computer program. In initial sessions, all participants demonstrated no consistent preference or preference for restricted choice. Differential reinforcement of free-choice selections resulted in increased preference for free choice immediately and in subsequent sessions in the absence of programmed differential outcomes. For 5 participants, changes in preference for choice were both robust and lasting, suggesting that a history of differential reinforcement for choice may affect preference for choice. PMID:21541125

Effects of a history of differential reinforcement on preference for choice.

PubMed

Karsina, Allen; Thompson, Rachel H; Rodriguez, Nicole M

2011-03-01

The effects of a history of differential reinforcement for selecting a free-choice versus a restricted-choice stimulus arrangement on the subsequent responding of 7 undergraduates in a computer-based game of chance were examined using a concurrent-chains arrangement and a multiple-baseline-across-participants design. In the free-choice arrangement, participants selected three numbers, in any order, from an array of eight numbers presented on the computer screen. In the restricted-choice arrangement, participants selected the order of three numbers preselected from the array of eight by a computer program. In initial sessions, all participants demonstrated no consistent preference or preference for restricted choice. Differential reinforcement of free-choice selections resulted in increased preference for free choice immediately and in subsequent sessions in the absence of programmed differential outcomes. For 5 participants, changes in preference for choice were both robust and lasting, suggesting that a history of differential reinforcement for choice may affect preference for choice.

The close relationship between estimated divergent selection and observed differentiation supports the selective origin of a marine snail hybrid zone.

PubMed

Cruz, R; Vilas, C; Mosquera, J; García, C

2004-11-01

To study the role of divergent selection in the differentiation of the two morphs in a hybrid zone of the intertidal snail Littorina saxatilis, we compared the strength of the divergent selection acting on a series of shell characters (as estimated by the viability of snails in a reciprocal transplant experiment) with the contribution of these characters to the phenotypic differences between the morphs. We found a close correlation between selection and differentiation, which suggests a cause-effect relationship, i.e. that all present differentiation is the result of past divergent selection. In addition, divergent selection was a very important component of the total natural selection acting on shell measures. These novel results support previous evidence, based on allozyme analysis, of a parapatric origin for this hybrid zone. We discuss possible limitations of this interpretation and the circumstances under which allopatric differentiation would produce the same results. Phenotypic analysis of divergent selection may be a useful method of investigating the evolutionary mechanisms involved in differentiation processes.

Differential effects of the classroom on African American and non-African American's mathematics achievement.

PubMed

Schenke, Katerina; Nguyen, Tutrang; Watts, Tyler W; Sarama, Julie H; Clements, Douglas H

2017-08-01

We examined whether African American students differentially responded to dimensions of the observed classroom-learning environment compared with non-African American students. Further, we examined whether these dimensions of the classroom mediated treatment effects of a preschool mathematics intervention targeted at students from low-income families. Three observed dimensions of the classroom (teacher expectations and developmental appropriateness; teacher confidence and enthusiasm; and support for mathematical discourse) were evaluated in a sample of 1,238 preschool students in 101 classrooms. Using multigroup multilevel mediation where African American students were compared to non-African American students, we found that teachers in the intervention condition had higher ratings on the observed dimensions of the classroom compared with teachers in the control condition. Further, ratings on teacher expectations and developmental appropriateness had larger associations with the achievement of African American students than for non-African Americans. Findings suggest that students within the same classroom may react differently to that learning environment and that classroom learning environments could be structured in ways that are beneficial for students who need the most support.

Incorporating prior knowledge induced from stochastic differential equations in the classification of stochastic observations.

PubMed

Zollanvari, Amin; Dougherty, Edward R

2016-12-01

In classification, prior knowledge is incorporated in a Bayesian framework by assuming that the feature-label distribution belongs to an uncertainty class of feature-label distributions governed by a prior distribution. A posterior distribution is then derived from the prior and the sample data. An optimal Bayesian classifier (OBC) minimizes the expected misclassification error relative to the posterior distribution. From an application perspective, prior construction is critical. The prior distribution is formed by mapping a set of mathematical relations among the features and labels, the prior knowledge, into a distribution governing the probability mass across the uncertainty class. In this paper, we consider prior knowledge in the form of stochastic differential equations (SDEs). We consider a vector SDE in integral form involving a drift vector and dispersion matrix. Having constructed the prior, we develop the optimal Bayesian classifier between two models and examine, via synthetic experiments, the effects of uncertainty in the drift vector and dispersion matrix. We apply the theory to a set of SDEs for the purpose of differentiating the evolutionary history between two species.

Toddlers' Differential Susceptibility to the Effects of Coparenting on Social-Emotional Adjustment

ERIC Educational Resources Information Center

Altenburger, Lauren E.; Lang, Sarah N.; Schoppe-Sullivan, Sarah J.; Kamp Dush, Claire M.; Johnson, Susan

2017-01-01

The paper reports on a study which tested whether infants high in negative affectivity are differentially susceptible to observed coparenting behavior in relation to their subsequent social-emotional development. Data came from a longitudinal study of 182 US dual-earner, primiparous couples and their infant children. At nine-months postpartum,…

OBSERVATIONS OF BINARY STARS WITH THE DIFFERENTIAL SPECKLE SURVEY INSTRUMENT. III. MEASURES BELOW THE DIFFRACTION LIMIT OF THE WIYN TELESCOPE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Horch, Elliott P.; Van Altena, William F.; Howell, Steve B.

2011-06-15

In this paper, we study the ability of CCD- and electron-multiplying-CCD-based speckle imaging to obtain reliable astrometry and photometry of binary stars below the diffraction limit of the WIYN 3.5 m Telescope. We present a total of 120 measures of binary stars, 75 of which are below the diffraction limit. The measures are divided into two groups that have different measurement accuracy and precision. The first group is composed of standard speckle observations, that is, a sequence of speckle images taken in a single filter, while the second group consists of paired observations where the two observations are taken onmore » the same observing run and in different filters. The more recent paired observations were taken simultaneously with the Differential Speckle Survey Instrument, which is a two-channel speckle imaging system. In comparing our results to the ephemeris positions of binaries with known orbits, we find that paired observations provide the opportunity to identify cases of systematic error in separation below the diffraction limit and after removing these from consideration, we obtain a linear measurement uncertainty of 3-4 mas. However, if observations are unpaired or if two observations taken in the same filter are paired, it becomes harder to identify cases of systematic error, presumably because the largest source of this error is residual atmospheric dispersion, which is color dependent. When observations are unpaired, we find that it is unwise to report separations below approximately 20 mas, as these are most susceptible to this effect. Using the final results obtained, we are able to update two older orbits in the literature and present preliminary orbits for three systems that were discovered by Hipparcos.« less

Assessing neurodevelopmental effects of arsenolipids in pre-differentiated human neurons.

PubMed

Witt, Barbara; Ebert, Franziska; Meyer, Sören; Francesconi, Kevin A; Schwerdtle, Tanja

2017-11-01

In the general population exposure to arsenic occurs mainly via diet. Highest arsenic concentrations are found in seafood, where arsenic is present predominantly in its organic forms including arsenolipids. Since recent studies have provided evidence that arsenolipids could reach the brain of an organism and exert toxicity in fully differentiated human neurons, this work aims to assess the neurodevelopmental toxicity of arsenolipids. Neurodevelopmental effects of three arsenic-containing hydrocarbons (AsHC), two arsenic-containing fatty acids (AsFA), arsenite and dimethylarsinic acid (DMA V ) were characterized in pre-differentiated human neurons. AsHCs and arsenite caused substantial cytotoxicity in a similar, low concentration range, whereas AsFAs and DMA V were less toxic. AsHCs were highly accessible for cells and exerted pronounced neurodevelopmental effects, with neurite outgrowth and the mitochondrial membrane potential being sensitive endpoints; arsenite did not substantially decrease those two endpoints. In fully differentiated neurons, arsenite and AsHCs caused neurite toxicity. These results indicate for a neurodevelopmental potential of AsHCs. Taken into account the possibility that AsHCs might easily reach the developing brain when exposed during early life, neurotoxicity and neurodevelopmental toxicity cannot be excluded. Further studies are needed in order to progress the urgently needed risk assessment. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

All-Printed Differential Temperature Sensor for the Compensation of Bending Effects.

PubMed

Ali, Shawkat; Hassan, Arshad; Bae, Jinho; Lee, Chong Hyun; Kim, Juho

2016-11-08

Because printed resistance temperature detectors (RTDs) are affected by tension and compression of metallic patterns on flexible or curved surfaces, a significant temperature-sensing error occurs in general. Hence, we propose a differential temperature sensor (DTS) to compensate the bending effect of the printed RTDs, which is composed of two serially connected similar meander patterns fabricated back-to-back on a polyimide polyethylene terephthalate substrate through a Dimatix DMP-3000 inkjet printer using silver nanoparticles. Under mechanical deformation, the resistance of the proposed DTS is not varied significantly under the same temperature environment because its patterns vary differentially as one side experiences tension while the opposite side experiences compression. A single meander pattern of the proposed DTS has a total length of 75 mm and device dimensions of 7 × 7 mm 2 . The total resistance variation is observed to be 15.5 Ω against the temperature variation from 0 to 100 °C, and the temperature coefficient of resistance is 1.076 × 10 -3 °C -1 . The proposed DTS exhibits no significant resistance change on bendability testing down to 2 mm diameter because of mechanical deformation. In addition, it is also used to detect the curvature of a body shape down to 2 mm diameter because its resistance changes by ±8.22% using a single meander pattern of DTS. The proposed sensor can be applied on a curved or flexible surface to measure relatively accurate temperature when compared to a single meander pattern.

Fluorescence and photodynamic effects of bacteriochlorin a observed in vivo in 'sandwich' observation chambers.

PubMed Central

van Leengoed, H. L.; Schuitmaker, J. J.; van der Veen, N.; Dubbelman, T. M.; Star, W. M.

1993-01-01

Bacteriochlorin a (BCA), a derivative of bacteriochlorphyll a, is an effective photosensitiser in vitro and in vivo. BCA has a major absorption peak at 760 nm where tissue penetration is optimal. This property, together with rapid tissue clearance promises minor skin photosensitivity. The tissue localising and photodynamic properties of BCA were studied using isogeneic RMA mammary tumours, transplanted into subcutaneous tissue in transparent 'sandwich' observation chambers on the back of WAG/Rij rats. The fluorescence kinetics following an i.v. administration of 20 mg kg-1 BCA was assessed in blood vessels, tumour and normal tissue. Subsequently, the development of vascular- and tissue damage after a therapeutic light dose (760 nm, 600 J cm-2) was observed. Fifteen minutes post injection (p.i.), the fluorescence of BCA in the tumour reached a plateau value of 2.5 times the fluorescence in the normal tissue. From 1 h post injection the tumour fluorescence diminished gradually; after 24 h, the tumour fluorescence signal did not exceed that of the normal tissue. Following photodynamic therapy (PDT), 24 h p.i., complete vascular stasis was observed 2 h post treatment in the tumour only, with subsequent recovery. The presence of viable tumour cells following PDT was assessed by histology and re-transplantation of treated tumour tissue from the chamber into the flank immediately or 7 days after treatment. In both cases tumour regrowth was observed. BCA-PDT (20 mg kg-1, 760 nm, 100 J cm-2) 1 h after BCA administration, an interval which gives the optimal differential between tumour and normal tissue, was sufficient to prevent tumour regrowth. However, this only occurred when re-transplantation was performed 7 days after PDT. During PDT, 1 h p.i., vascular damage in tumour and normal tissue was considerable. Complete vascular shut-down was observed in the tumour 2 h after therapy and in the surrounding tissues at 24 h. Circulation damage was associated with vascular spasm

Effects of intermittent versus continuous parathyroid hormone administration on condylar chondrocyte proliferation and differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Qi; Wan, Qilong; Yang, Rongtao

Highlights: Black-Right-Pointing-Pointer Different PTH administration exerts different effects on condylar chondrocyte. Black-Right-Pointing-Pointer Intermittent PTH administration suppresses condylar chondrocyte proliferation. Black-Right-Pointing-Pointer Continuous PTH administration maintains condylar chondrocyte proliferating. Black-Right-Pointing-Pointer Intermittent PTH administration enhances condylar chondrocyte differentiation. -- Abstract: Endochondral ossification is a complex process involving chondrogenesis and osteogenesis regulated by many hormones and growth factors. Parathyroid hormone (PTH), one of the key hormones regulating bone metabolism, promotes osteoblast differentiation and osteogenesis by intermittent administration, whereas continuous PTH administration inhibits bone formation. However, the effects of PTH on chondrocyte proliferation and differentiation are still unclear. In this study, intermittent PTH administration presentedmore » enhanced effects on condylar chondrocyte differentiation and bone formation, as demonstrated by increased mineral nodule formation and alkaline phosphatase (ALP) activity, up-regulated runt-related transcription factor 2 (RUNX2), ALP, collagen type X (COL10a1), collagen type I (COL1a1), osteocalcin (OCN), bone sialoprotein (BSP), bone morphogenetic protein 2 (BMP2) and osterix (OSX) mRNA and/or protein expression. On the contrary, continuous PTH administration promoted condylar chondrocyte proliferation and suppressed its differentiation, as demonstrated by up-regulated collagen type II (COL2a1) mRNA expression, reduced mineral nodule formation and down-regulated expression of the mRNAs and/or proteins mentioned above. Our data suggest that PTH can regulate condylar chondrocyte proliferation and differentiation, depending on the type of PTH administration. These results provide new insight into the effects of PTH on condylar chondrocytes and new evidence for using local PTH administration to cure

METHYLMERCURY IMPAIRS NEURONAL DIFFERENTIATION BY ALTERING NEUROTROPHIN SIGNALING.

EPA Science Inventory

In previous in vivo studies, we observed that developmental exposure to CH3Hg can alter neocortical morphology and neurotrophin signaling. Using primed PC12 cells as a model system for neuronal differentiation, we examined the hypothesis that the developmental effects of CH3Hg ma...

Effects of water extract of Cajanus cajan leaves on the osteogenic and adipogenic differentiation of mouse primary bone marrow stromal cells and the adipocytic trans-differentiation of mouse primary osteoblasts.

PubMed

Zhang, Jinchao; Liu, Cuilian; Sun, Jing; Liu, Dandan; Wang, Peng

2010-01-01

The effects of water extract of Cajanus cajan (Linn.) Millsp. (Leguminosae) leaves (WECML) on the osteogenic and adipogenic differentiation of mouse primary bone marrow stromal cells (BMSCs) and the adipocytic trans-differentiation of mouse primary osteoblasts (OBs) were studied. The results indicated that WECML promoted the proliferation of BMSCs and OBs at most concentrations. WECML promoted the osteogenic differentiation and formation of mineralized matrix nodules of BMSCs at concentrations of 0.1, 1, and 10 microg/mL, but inhibited the osteogenic differentiation and formation of mineralized matrix nodules of BMSCs at concentration of 0.01 microg/mL. WECML inhibited the adipogenic differentiation of BMSCs and adipocytic trans-differentiation of OBs at concentrations of 0.001, 0.1, 1, 10, and 100 microg/mL, but had no effects at concentration of 0.01 microg/mL. The results suggest that WECML has protective effects on bone and these protective effects may be mediated by decreasing adipocytic cell formation from BMSCs, which may promote the proliferation, differentiation, and mineralization function of OBs. The defined active ingredients in the WECML and the active mechanism need to be further studied.

Disability differentials in educational attainment in England: primary and secondary effects.

PubMed

Chatzitheochari, Stella; Platt, Lucinda

2018-04-17

Childhood disability has been largely overlooked in social stratification and life course research. As a result, we know remarkably little about mechanisms behind well-documented disability differentials in educational outcomes. This study investigates educational transitions of disabled youth using data from the Longitudinal Study of Young People in England. We draw on social stratification literature on primary and secondary effects as well as that on stigma and labelling in order to explain disabled young people's educational outcomes. We find that disability differentials in transition rates to full-time academic upper secondary education and to university are largely the result of primary effects, reflected in differences in school performance between disabled and non-disabled young people. However, we also find evidence for secondary effects, with similarly achieving disabled young people less likely to pursue full-time academic upper secondary education compared to their non-disabled peers. We examine the extent to which these effects can be explained by disabled youth's suppressed educational expectations as well as their experiences of being bullied at school, which we link to the stigma experienced by disabled young people and their families. We find that educational expectations play an important role at crucial transitions in the English school system, while the effect of bullying is considerably smaller. By drawing attention to different social processes contributing to disability differentials in attainment, our study moves beyond medical models that implicitly assume a naturalized association of disability with poor educational outcomes, and demonstrates the parallels of disability with other ascriptive inequalities. © London School of Economics and Political Science 2018.

Differentiating the effects of status and power: a justice perspective.

PubMed

Blader, Steven L; Chen, Ya-Ru

2012-05-01

Few empirical efforts have been devoted to differentiating status and power, and thus significant questions remain about differences in how status and power impact social encounters. We conducted 5 studies to address this gap. In particular, these studies tested the prediction that status and power would have opposing effects on justice enacted toward others. In the first 3 studies, we directly compared the effects of status and power on people's enactment of distributive (Study 1) and procedural (Studies 2 and 3) justice. In the last 2 studies, we orthogonally manipulated status and power and examined their main and interactive effects on people's enactment of distributive (Study 4) and procedural (Study 5) justice. As predicted, all 5 studies showed consistent evidence that status is positively associated with justice toward others, while power is negatively associated with justice toward others. The effects of power are moderated, however, by an individual's other orientation (Studies 2, 3, 4, and 5), and the effects of status are moderated by an individual's dispositional concern about status (Study 5). Furthermore, Studies 4 and 5 also demonstrated that status and power interact, such that the positive effect of status on justice emerges when power is low and not when power is high, providing further evidence for differential effects between power and status. Theoretical implications for the literatures on status, power, and distributive/procedural justice are discussed.

The Differential Effects of Reward on Space- and Object-Based Attentional Allocation

PubMed Central

Shomstein, Sarah

2013-01-01

Estimating reward contingencies and allocating attentional resources to a subset of relevant information are the most important contributors to increasing adaptability of an organism. Although recent evidence suggests that reward- and attention-based guidance recruits overlapping cortical regions and has similar effects on sensory responses, the exact nature of the relationship between the two remains elusive. Here, using event-related fMRI on human participants, we contrasted the effects of reward on space- and object-based selection in the same experimental setting. Reward was either distributed randomly or biased a particular object. Behavioral and neuroimaging results show that space- and object-based attention is influenced by reward differentially. Space-based attentional allocation is mandatory, integrating reward information over time, whereas object-based attentional allocation is a default setting that is completely replaced by the reward signal. Nonadditivity of the effects of reward and object-based attention was observed consistently at multiple levels of analysis in early visual areas as well as in control regions. These results provide strong evidence that space- and object-based allocation are two independent attentional mechanisms, and suggest that reward serves to constrain attentional selection. PMID:23804086

Differentiating Sudden Loss Mechanisms of Inner-belt Protons from Multisatellite Observations

NASA Astrophysics Data System (ADS)

Chen, Y.; Henderson, M. G.; Reeves, G. D.; Baker, D. N.; Lanzerotti, L. J.; Blake, J. B.; Mazur, J. E.; Spence, H.; Mitchell, D. G.

2013-12-01

Energetic protons (with kinetic energy from several to ~100 MeV) residing in the inner Van Allen belt region are usually stable except when disturbed by transient events such as interplanetary (IP) shocks. When a strong IP shock accompanied by a large population of solar energetic protons impinges the Earth's magnetosphere, it is often observed that a new proton belt emerges at L-shells ~2.5-3.5. One plausible explanation for these new protons is that, after the penetrating solar protons load a seed population at medium L-shells, those protons are promptly transported inward to low L-shells by impulsive shock-induced electric fields and adiabatically accelerated to higher energies. However, the mechanism for the sudden loss--i.e., the new proton belt may disappear with another impinging IP shock--it is still an open question, and three hypotheses currently exist. The first is the loss due to strengthened scattering from the build-up of the ring current. Another mechanism is that the shock-induced electric field will further move preexisting protons toward the Earth, causing the apparent sudden losses at some L-shells. The third loss process is that shock-induced ULF waves may outward diffuse protons along the direction of radial gradient in the proton distribution. A systematic examination of particle and field observations is required to differentiate among these three loss hypotheses. Here we analyze two sets of satellite observations: One is from past missions including HEO-3 (measuring at low-latitude), Polar (mid-latitude), and SAMPEX (high-latitude); the other set is from the operating Van Allen Probes mission. The first data set covers a long time interval (1998-2007), including a list of loss events, and the multi-point measurements enable us to investigate the pitch-angle- and energy- dependences of losses in the inner belt region. The second data set has the most comprehensive coverage of energy and pitch-angle as well as very high time resolutions, which

Lamin A/C Haploinsufficiency Modulates the Differentiation Potential of Mouse Embryonic Stem Cells

PubMed Central

Sehgal, Poonam; Chaturvedi, Pankaj; Kumaran, R. Ileng; Kumar, Satish; Parnaik, Veena K.

2013-01-01

Background Lamins are structural proteins that are the major determinants of nuclear architecture and play important roles in various nuclear functions including gene regulation and cell differentiation. Mutations in the human lamin A gene cause a spectrum of genetic diseases that affect specific tissues. Most available mouse models for laminopathies recapitulate disease symptoms for muscle diseases and progerias. However, loss of human lamin A/C also has highly deleterious effects on fetal development. Hence it is important to understand the impact of lamin A/C expression levels on embryonic differentiation pathways. Methodology and Principal Findings We have investigated the differentiation potential of mouse embryonic stem cells containing reduced levels of lamin A/C by detailed lineage analysis of embryoid bodies derived from these cells by in vitro culture. We initially carried out a targeted disruption of one allele of the mouse lamin A/C gene (Lmna). Undifferentiated wild-type and Lmna+/− embryonic stem cells showed similar expression of pluripotency markers and cell cycle profiles. Upon spontaneous differentiation into embryoid bodies, markers for visceral endoderm such as α-fetoprotein were highly upregulated in haploinsufficient cells. However, neuronal markers such as β-III tubulin and nestin were downregulated. Furthermore, we observed a reduction in the commitment of Lmna+/− cells into the myogenic lineage, but no discernible effects on cardiac, adipocyte or osteocyte lineages. In the next series of experiments, we derived embryonic stem cell clones expressing lamin A/C short hairpin RNA and examined their differentiation potential. These cells expressed pluripotency markers and, upon differentiation, the expression of lineage-specific markers was altered as observed with Lmna+/− embryonic stem cells. Conclusions We have observed significant effects on embryonic stem cell differentiation to visceral endoderm, neuronal and myogenic lineages upon

Effect of boron on osteogenic differentiation of human bone marrow stromal cells.

PubMed

Ying, Xiaozhou; Cheng, Shaowen; Wang, Wei; Lin, Zhongqin; Chen, Qingyu; Zhang, Wei; Kou, Dongquan; Shen, Yue; Cheng, Xiaojie; Rompis, Ferdinand An; Peng, Lei; Zhu Lu, Chuan

2011-12-01

Bone marrow stromal cells (BMSCs) have been well established as an ideal source of cell-based therapy for bone tissue engineering applications. Boron (B) is a notable trace element in humans; so far, the effects of boron on the osteogenic differentiation of BMSCs have not been reported. The aim of this study was to evaluate the effects of boron (0, 1, 10,100, and 1,000 ng/ml) on osteogenic differentiation of human BMSCs. In this study, BMSCs proliferation was analyzed by cell counting kit-8 (CCK8) assay, and cell osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity assay, Von Kossa staining, and real-time PCR. The results indicated that the proliferation of BMSCs was no different from the control group when added with B at the concentration of 1, 10, and 100 ng/ml respectively (P > 0.05); in contrast, 1,000 ng/ml B inhibited the proliferation of BMSCs at days 4, 7, and 14 (P < 0.05). By ALP staining, we discovered that BMSCs treated with 10 and 100 ng/ml B presented a higher ALP activity compared with control (P < 0.05). By real-time PCR, we detected the messenger RNA expression of ALP, osteocalcin, collagen type I, and bone morphogenetic proteins 7 were also increased in 10 and 100 ng/ml B treatment groups (P < 0.05). The calcium depositions were increased in 1 and 10 ng/ml B treatment groups (P < 0.05). Taken all together, it was the first time to report that B could increase osteogenic effect by stimulating osteogenic differentiation-related marker gene synthesis during the proliferation and differentiation phase in human BMSCs and could be a promising approach for enhancing osteogenic capacity of cell-based construction in bone tissue engineering.

The Effect of Laser Irradiation on Adipose Derived Stem Cell Proliferation and Differentiation

NASA Astrophysics Data System (ADS)

Abrahamse, H.; de Villiers, J.; Mvula, B.

2009-06-01

There are two fundamental types of stem cells: Embryonic Stem cells and Adult Stem cells. Adult Stem cells have a more restricted potential and can usually differentiate into a few different cell types. In the body these cells facilitate the replacement or repair of damaged or diseased cells in organs. Low intensity laser irradiation was shown to increase stem cell migration and stimulate proliferation and it is thought that treatment of these cells with laser irradiation may increase the stem cell harvest and have a positive effect on the viability and proliferation. Our research is aimed at determining the effect of laser irradiation on differentiation of Adipose Derived Stem Cells (ADSCs) into different cell types using a diode laser with a wavelength of 636 nm and at 5 J/cm2. Confirmation of stem cell characteristics and well as subsequent differentiation were assessed using Western blot analysis and cellular morphology supported by fluorescent live cell imaging. Functionality of subsequent differentiated cells was confirmed by measuring adenosine triphosphate (ATP) production and cell viability.

Effect of low-level diode laser on proliferation and osteogenic differentiation of dental pulp stem cells

NASA Astrophysics Data System (ADS)

Tabatabaei, Fahimeh S.; Torshabi, Maryam; Mojahedi Nasab, Masoud; Khosraviani, Keikhosro; Khojasteh, Arash

2015-09-01

This study assessed the effect of low-level laser irradiation (LLLI) on the proliferation and osteogenic differentiation of dental pulp stem cells (DPSCs). DPSCs were exposed to 810 nm laser light (0.1, 0.2, or 0.3 J cm-2) for 7 d (60 s daily). The negative control group (cells in regular medium) and positive control group (cells in osteogenic medium (OM)) were not lased. One group of cells in OM was irradiated with laser operated at 0.2 J cm-2. Cell viability was evaluated at 24 h and one week after the last day of laser irradiation using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Osteogenic differentiation was assessed using real-time reverse transcriptase polymerase chain reaction (RT-PCR) and alizarin Red S staining. Cell proliferation was not affected by laser irradiation at 24 h except in one group (cells in OM exposed to laser at 0.2 J cm-2). However, one week after the last day of laser irradiation, it was significantly increased in groups exposed to laser at 0.1 or 0.2 J cm-2 and decreased in groups containing OM (P  <  0.05). Osteoblast marker expression was observed in groups containing OM. LLLI at 0.2 J cm-2 dramatically enhanced cell differentiation. Laser at 0.3 J cm-2 increased bone sialoprotein (BSP) and decreased alkaline phosphatase (ALP). Mineralized nodules were only observed in groups containing OM. Considering these findings, LLLI may be used as a novel approach for preconditioning of DPSCs in vitro prior to bone tissue engineering.

The effects of perfluorinated chemicals on adipocyte differentiation in vitro.

PubMed

Watkins, Andrew M; Wood, Carmen R; Lin, Mimi T; Abbott, Barbara D

2015-01-15

The 3T3-L1 preadipocyte culture system has been used to examine numerous compounds that influence adipocyte differentiation or function. The perfluoroalkyl acids (PFAAs), used as surfactants in a variety of industrial applications, are of concern as environmental contaminants that are detected worldwide in human serum and animal tissues. This study was designed to evaluate the potential for PFAAs to affect adipocyte differentiation and lipid accumulation using mouse 3T3-L1 cells. Cells were treated with perfluorooctanoic acid (PFOA) (5-100 µM), perfluorononanoic acid (PFNA) (5-100 µM), perfluorooctane sulfonate (PFOS) (50-300 µM), perfluorohexane sulfonate (PFHxS) (40-250 µM), the peroxisome proliferator activated receptor (PPAR) PPARα agonist Wyeth-14,643 (WY-14,643), and the PPARγ agonist rosiglitazone. The PPARγ agonist was included as a positive control as this pathway is critical to adipocyte differentiation. The PPARα agonist was included as the PFAA compounds are known activators of this pathway. Cells were assessed morphometrically and biochemically for number, size, and lipid content. RNA was extracted for qPCR analysis of 13 genes selected for their importance in adipocyte differentiation and lipid metabolism. There was a significant concentration-related increase in cell number and decreased cell size after exposure to PFOA, PFHxS, PFOS, and PFNA. All four PFAA treatments produced a concentration-related decrease in the calculated average area occupied by lipid per cell. However, total triglyceride levels per well increased with a concentration-related trend for all compounds, likely due to the increased cell number. Expression of mRNA for the selected genes was affected by all exposures and the specific impacts depended on the particular compound and concentration. Acox1 and Gapdh were upregulated by all six compounds. The strongest overall effect was a nearly 10-fold induction of Scd1 by PFHxS. The sulfonated PFAAs produced numerous

LL-37 directs macrophage differentiation toward macrophages with a proinflammatory signature.

PubMed

van der Does, Anne M; Beekhuizen, Henry; Ravensbergen, Bep; Vos, Tim; Ottenhoff, Tom H M; van Dissel, Jaap T; Drijfhout, Jan W; Hiemstra, Pieter S; Nibbering, Peter H

2010-08-01

The human cathelicidin LL-37 has broad-spectrum antimicrobial activity. It also participates at the interface of innate and adaptive immunity by chemoattracting immune effector cells, modulating the production of a variety of inflammatory mediators by different cell types, and regulating the differentiation of monocytes into dendritic cells. In this study, we investigated the effects of LL-37 on the differentiation of human monocytes into anti-inflammatory macrophages (MPhi-2; driven by M-CSF) versus proinflammatory macrophages (MPhi-1; driven by GM-CSF) as well as on fully differentiated MPhi-1 and MPhi-2. Results revealed that monocytes cultured with M-CSF in the presence of LL-37 resulted in macrophages displaying a proinflammatory signature, namely, low expression of CD163 and little IL-10 and profound IL-12p40 production on LPS stimulation. The effects of LL-37 on M-CSF-driven macrophage differentiation were dose- and time-dependent with maximal effects observed at 10 microg/ml when the peptide was present from the start of the cultures. The peptide enhanced the GM-CSF-driven macrophage differentiation. Exposure of fully differentiated MPhi-2 to LL-37 for 6 d resulted in macrophages that produced less IL-10 and more IL-12p40 on LPS stimulation than control MPhi-2. In contrast, LL-37 had no effect on fully differentiated MPhi-1. Peptide mapping using a set of 16 overlapping 22-mer peptides covering the complete LL-37 sequence revealed that the C-terminal portion of LL-37 is responsible for directing macrophage differentiation. Our results furthermore indicate that the effects of LL-37 on macrophage differentiation required internalization of the peptide. Together, we conclude that LL-37 directs macrophage differentiation toward macrophages with a proinflammatory signature.

[Observation in situ of differentiation from PGC to hematopoietic system cells in chicken embryo].

PubMed

Zhou, Dong-Yu; Liu, Rong-Xiu; Pei, Yue-Hu

2009-02-01

To study the relationship between hematopoiesis and primordial germ cells, chick embryos at different developing stages were flatbed and located. After fixed by glutaral, the embryos were PAS and HE stained respectively, dehydrated serially, transparent, mounted, and were observed in situ or in cut sheet condition. The results showed: (1) the cellule amorphous and the disposition in chick embryo of PGCs were coincident no matter stained by PAS or HE staining, and HE staining could disclose the morphologic characteristics more clearly, exactly and completely; (2) genesis of blood island could be observed at the boundary of light and dark region of the extraembryonic blastoderm at about 26 hours; (3) both the blood vessel endothelium cells and free cells of the blood island were differentiated from PGCs. The generating of genuine yolk sac was at about 44 - 48 hours. It is concluded that the initial anatomic site of blood island genesis may be is mesoblast of extraembryonic blastoderm rather than the yolk sac; the blood vessel endothelium cells and the blood cells are generated parallel; the PGCs are the common ancestry of angioblast and HSC.

An Effective Model of the Retinoic Acid Induced HL-60 Differentiation Program.

PubMed

Tasseff, Ryan; Jensen, Holly A; Congleton, Johanna; Dai, David; Rogers, Katharine V; Sagar, Adithya; Bunaciu, Rodica P; Yen, Andrew; Varner, Jeffrey D

2017-10-30

In this study, we present an effective model All-Trans Retinoic Acid (ATRA)-induced differentiation of HL-60 cells. The model describes reinforcing feedback between an ATRA-inducible signalsome complex involving many proteins including Vav1, a guanine nucleotide exchange factor, and the activation of the mitogen activated protein kinase (MAPK) cascade. We decomposed the effective model into three modules; a signal initiation module that sensed and transformed an ATRA signal into program activation signals; a signal integration module that controlled the expression of upstream transcription factors; and a phenotype module which encoded the expression of functional differentiation markers from the ATRA-inducible transcription factors. We identified an ensemble of effective model parameters using measurements taken from ATRA-induced HL-60 cells. Using these parameters, model analysis predicted that MAPK activation was bistable as a function of ATRA exposure. Conformational experiments supported ATRA-induced bistability. Additionally, the model captured intermediate and phenotypic gene expression data. Knockout analysis suggested Gfi-1 and PPARg were critical to the ATRAinduced differentiation program. These findings, combined with other literature evidence, suggested that reinforcing feedback is central to hyperactive signaling in a diversity of cell fate programs.

On polarimetric radar signatures of deep convection for model evaluation: columns of specific differential phase observed during MC3E

PubMed Central

van Lier-Walqui, Marcus; Fridlind, Ann M.; Ackerman, Andrew S.; Collis, Scott; Helmus, Jonathan; MacGorman, Donald R.; North, Kirk; Kollias, Pavlos; Posselt, Derek J.

2017-01-01

The representation of deep convection in general circulation models is in part informed by cloud-resolving models (CRMs) that function at higher spatial and temporal resolution; however, recent studies have shown that CRMs often fail at capturing the details of deep convection updrafts. With the goal of providing constraint on CRM simulation of deep convection updrafts, ground-based remote-sensing observations are analyzed and statistically correlated for four deep convection events observed during the Midlatitude Continental Convective Clouds Experiment (MC3E). Since positive values of specific differential phase (KDP) observed above the melting level are associated with deep convection updraft cells, so-called “KDP columns” are analyzed using two scanning polarimetric radars in Oklahoma: the National Weather Service Vance WSR-88D (KVNX) and the Department of Energy C-band Scanning Atmospheric Radiation Measurement (ARM) Precipitation Radar (C-SAPR). KVNX and C-SAPR KDP volumes and columns are then statistically correlated with vertical winds retrieved via multi-Doppler wind analysis, lightning flash activity derived from the Oklahoma Lightning Mapping Array, and KVNX differential reflectivity (ZDR). Results indicate strong correlations of KDP volume above the melting level with updraft mass flux, lightning flash activity, and intense rainfall. Analysis of KDP columns reveals signatures of changing updraft properties from one storm event to another as well as during event evolution. Comparison of ZDR to KDP shows commonalities in information content of each, as well as potential problems with ZDR associated with observational artifacts. PMID:29503466

On polarimetric radar signatures of deep convection for model evaluation: columns of specific differential phase observed during MC3E

DOE Office of Scientific and Technical Information (OSTI.GOV)

van Lier-Walqui, Marcus; Fridlind, Ann; Ackerman, Andrew S

2016-02-01

The representation of deep convection in general circulation models is in part informed by cloud-resolving models (CRMs) that function at higher spatial and temporal resolution; however, recent studies have shown that CRMs often fail at capturing the details of deep convection updrafts. With the goal of providing constraint on CRM simulation of deep convection updrafts, ground-based remote sensing observations are analyzed and statistically correlated for four deep convection events observed during the Midlatitude Continental Convective Clouds Experiment (MC3E). Since positive values of specific differential phase observed above the melting level are associated with deep convection updraft cells, so-called columns aremore » analyzed using two scanning polarimetric radars in Oklahoma: the National Weather Service Vance WSR-88D (KVNX) and the Department of Energy C-band Scanning Atmospheric Radiation Measurement (ARM) Precipitation Radar (C-SAPR). KVNX and C-SAPR volumes and columns are then statistically correlated with vertical winds retrieved via multi-Doppler wind analysis, lightning flash activity derived from the Oklahoma Lightning Mapping Array, and KVNX differential reflectivity . Results indicate strong correlations of volume above the melting level with updraft mass flux, lightning flash activity, and intense rainfall. Analysis of columns reveals signatures of changing updraft properties from one storm event to another as well as during event evolution. Comparison of to shows commonalities in information content of each, as well as potential problems with associated with observational artifacts.« less

Differential effects of reinforcement on the self-monitoring of on-task behavior.

PubMed

Otero, Tiffany L; Haut, Jillian M

2016-03-01

In the current study, the differential effects of reinforcement on a self-monitoring intervention were evaluated. Three students nominated by their teachers for having a marked difficultly maintaining on-task behaviors participated in the study. Using an alternating treatments single-case design to assess self-monitoring with and without reinforcement, students self-monitored their on-task behavior while being prompted by a vibrating timer at 1-min intervals for 20-min sessions. The investigators collected data regarding the students' percentage of intervals on-task and the accuracy of their recordings. Accuracy was measured by calculating the percent of agreement between the observer and student. For half of the self-monitoring sessions, students were provided reinforcement for matching at least 80% of their self-monitored ratings with those of the observer. Results indicated that self-monitoring alone was effective for 2 students in increasing their on-task behaviors in a general education classroom and self-monitoring with reinforcement was effective for all 3. Two students demonstrated an increase in on-task behavior when self-monitoring was paired with the opportunity to receive reinforcement compared to self-monitoring alone. Percentage of nonoverlapping data for self-monitoring without reinforcement ranged from 16.6% to 100%, and self-monitoring with reinforcement ranged from 83% to 100%. Additionally, the opportunity to receive reinforcement impacted students' accuracy in self-monitoring resulting in more accurate self-recording of on-task behavior. Including reinforcement as a component of a self-monitoring intervention package is an important consideration as it may impact the effectiveness of the intervention for students with significant difficulties maintaining attention to tasks. (c) 2016 APA, all rights reserved).

High-power flexible AlGaN/GaN heterostructure field-effect transistors with suppression of negative differential conductance

NASA Astrophysics Data System (ADS)

Oh, Seung Kyu; Cho, Moon Uk; Dallas, James; Jang, Taehoon; Lee, Dong Gyu; Pouladi, Sara; Chen, Jie; Wang, Weijie; Shervin, Shahab; Kim, Hyunsoo; Shin, Seungha; Choi, Sukwon; Kwak, Joon Seop; Ryou, Jae-Hyun

2017-09-01

We investigate thermo-electronic behaviors of flexible AlGaN/GaN heterostructure field-effect transistors (HFETs) for high-power operation of the devices using Raman thermometry, infrared imaging, and current-voltage characteristics. A large negative differential conductance observed in HFETs on polymeric flexible substrates is confirmed to originate from the decreasing mobility of the two-dimensional electron gas channel caused by the self-heating effect. We develop high-power transistors by suppressing the negative differential conductance in the flexible HFETs using chemical lift-off and modified Ti/Au/In metal bonding processes with copper (Cu) tapes for high thermal conductivity and low thermal interfacial resistance in the flexible hybrid structures. Among different flexible HFETs, the ID of the HFETs on Cu with Ni/Au/In structures decreases only by 11.3% with increasing drain bias from the peak current to the current at VDS = 20 V, which is close to that of the HFETs on Si (9.6%), solving the problem of previous flexible AlGaN/GaN transistors.

The differential effects of rail rate deregulation : U.S. corn, wheat, and soybean markets

DOT National Transportation Integrated Search

2003-06-01

It is important to understand the distribution and incidence of influences associated with deregulation of rail rates. The objective of this research was to provide insight into inter- and intra-commodity rail rate differentials observed since rates ...

Differential respiratory health effects from the 2008 northern California wildfires: A spatiotemporal approach.

PubMed

Reid, Colleen E; Jerrett, Michael; Tager, Ira B; Petersen, Maya L; Mann, Jennifer K; Balmes, John R

2016-10-01

We investigated health effects associated with fine particulate matter during a long-lived, large wildfire complex in northern California in the summer of 2008. We estimated exposure to PM2.5 for each day using an exposure prediction model created through data-adaptive machine learning methods from a large set of spatiotemporal data sets. We then used Poisson generalized estimating equations to calculate the effect of exposure to 24-hour average PM2.5 on cardiovascular and respiratory hospitalizations and ED visits. We further assessed effect modification by sex, age, and area-level socioeconomic status (SES). We observed a linear increase in risk for asthma hospitalizations (RR=1.07, 95% CI=(1.05, 1.10) per 5µg/m(3) increase) and asthma ED visits (RR=1.06, 95% CI=(1.05, 1.07) per 5µg/m(3) increase) with increasing PM2.5 during the wildfires. ED visits for chronic obstructive pulmonary disease (COPD) were associated with PM2.5 during the fires (RR=1.02 (95% CI=(1.01, 1.04) per 5µg/m(3) increase) and this effect was significantly different from that found before the fires but not after. We did not find consistent effects of wildfire smoke on other health outcomes. The effect of PM2.5 during the wildfire period was more pronounced in women compared to men and in adults, ages 20-64, compared to children and adults 65 or older. We also found some effect modification by area-level median income for respiratory ED visits during the wildfires, with the highest effects observed in the ZIP codes with the lowest median income. Using a novel spatiotemporal exposure model, we found some evidence of differential susceptibility to exposure to wildfire smoke. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of meteoroid fragmentation on radar observations of meteor trails

NASA Astrophysics Data System (ADS)

Elford, W. Graham; Campbell, L.

2001-11-01

Radar reflections from meteor trails often differ from the predictions of simple models. There is general consensus that these differences are probably the result of fragmentation of the meteoroid. Several examples taken from different types of meteor radar observations are considered in order to test the validity of the fragmentation hypothesis. The absence of the expected Fresnel oscillations in many observations of transverse scatter from meteor trails is readily explained by assuming a number of ablating fragments spread out along the trails. Observations of amplitude fluctuations in head echoes from "down-the-beam" meteoroids are explained by gross fragmentation of a meteoroid into two or more pieces. Another down-the-beam event is modeled by simulation of the differential retardation of two fragments of different mass, giving reasonable agreement between the observed and predicted radar signals.

Immunoregulatory effects of glutathione during mesenchymal stem cell differentiation to hepatocyte-like cells.

PubMed

Ahmadi-Ashtiani, Hamid-Reza; Allameh, Abdolamir; Rastegar, Hossein; Mortaz, Esmaeil; Saraf, Zahir

2012-09-01

The role of mesenchymal stem cell in cellular therapy is the subject of interest for many researchers. The differentiation potential of MSCs and abilities in modulations of the recipient's immune system makes them important cells in tissue regenerative studies. MSCs by releasing the proinflammatory cytokines play important role in immunomodulatory systems; however the signaling pathways for releasing of these mediators are not well understood. Glutathione has been shown to play a role in modulation of cytokines in hepatogenic differentiation. In the current study we aimed to investigate the effects of buthionine sulfoximine (BSO, inhibitor for glutathione synthesis) and N-acetylecystin (NAC, an inhibitor for ROS generation) on proinflammatory cytokines production in a hepatogenic differentiation model. BSO and NAC significantly decreased IL-6 and TNF-α levels at 14 days of differentiation, whereas, NAC decreased the levels of IL-8 at days 2 and 14 of differentiation. Moreover, intracellular glutathione level during the differentiation was depleted. Our current study suggests a novel role of GSH as an immunopharmacological regulatory molecule during hepatogenic differentiation. Finally, this information may shed some light on the understanding of MSCs responses in transplantation and cell therapy in diseases such as chronic hepatic diseases.

Role of Alternative Polyadenylation during Adipogenic Differentiation: An In Silico Approach

PubMed Central

Spangenberg, Lucía; Correa, Alejandro; Dallagiovanna, Bruno; Naya, Hugo

2013-01-01

Post-transcriptional regulation of stem cell differentiation is far from being completely understood. Changes in protein levels are not fully correlated with corresponding changes in mRNAs; the observed differences might be partially explained by post-transcriptional regulation mechanisms, such as alternative polyadenylation. This would involve changes in protein binding, transcript usage, miRNAs and other non-coding RNAs. In the present work we analyzed the distribution of alternative transcripts during adipogenic differentiation and the potential role of miRNAs in post-transcriptional regulation. Our in silico analysis suggests a modest, consistent, bias in 3′UTR lengths during differentiation enabling a fine-tuned transcript regulation via small non-coding RNAs. Including these effects in the analyses partially accounts for the observed discrepancies in relative abundance of protein and mRNA. PMID:24143171

Differential Effects of Explicit Form-Focused Instruction on Morphosyntactic Development

ERIC Educational Resources Information Center

Xu, Hainu; Lyster, Roy

2014-01-01

This study explores whether and to what degree explicit form-focused instruction (FFI) facilitates the use of morphosyntactic forms in second language oral production and also whether it has differential effects on morphosyntactic forms with different linguistic variables. Twenty-seven university-level Chinese EFL participants were randomly…

Differential Effects of Social Networks on Mammography Use by Poverty Status.

PubMed

Yeo, Younsook

2016-01-01

This study examines whether social networks have differential effects on mammography use depending on poverty status. Data were analyzed on US women (40+), employing logistic regression and simple slope analyses for a post hoc probing of moderating effects. Among women not in poverty, living with a spouse/partner and attending church, regardless of frequency, were positively associated with mammography use; family size was negatively associated. Among women living in poverty, mammography showed a positive association only with weekly church attendance. Mammography was negatively associated with health-related social interactions occurring through the Internet. Post hoc probing showed significant moderating effects of poverty on the relationship between online health-related interactions and mammography use. To make the Internet a meaningful health empowerment tool for women in poverty, future research should identify how health-related interactions that occur online affect women in poverty's psychological and behavioral reactions that will contribute to our understanding of why they are discouraged from having mammograms. The mechanisms behind the differential effects of church attendance and poverty status on mammography also need further clarification.

Selection for niche differentiation in plant communities increases biodiversity effects.

PubMed

Zuppinger-Dingley, Debra; Schmid, Bernhard; Petermann, Jana S; Yadav, Varuna; De Deyn, Gerlinde B; Flynn, Dan F B

2014-11-06

In experimental plant communities, relationships between biodiversity and ecosystem functioning have been found to strengthen over time, a fact often attributed to increased resource complementarity between species in mixtures and negative plant-soil feedbacks in monocultures. Here we show that selection for niche differentiation between species can drive this increasing biodiversity effect. Growing 12 grassland species in test monocultures and mixtures, we found character displacement between species and increased biodiversity effects when plants had been selected over 8 years in species mixtures rather than in monocultures. When grown in mixtures, relative differences in height and specific leaf area between plant species selected in mixtures (mixture types) were greater than between species selected in monocultures (monoculture types). Furthermore, net biodiversity and complementarity effects were greater in mixtures of mixture types than in mixtures of monoculture types. Our study demonstrates a novel mechanism for the increase in biodiversity effects: selection for increased niche differentiation through character displacement. Selection in diverse mixtures may therefore increase species coexistence and ecosystem functioning in natural communities and may also allow increased mixture yields in agriculture or forestry. However, loss of biodiversity and prolonged selection of crops in monoculture may compromise this potential for selection in the longer term.

Differential scanning calorimetry of coal

NASA Technical Reports Server (NTRS)

Gold, P. I.

1978-01-01

Differential scanning calorimetry studies performed during the first year of this project demonstrated the occurrence of exothermic reactions associated with the production of volatile matter in or near the plastic region. The temperature and magnitude of the exothermic peak were observed to be strongly affected by the heating rate, sample mass and, to a lesser extent, by sample particle size. Thermal properties also were found to be influenced by oxidation of the coal sample due to weathering effects.

Evaluating the effectiveness of wildlife detection and observation technologies at a solar power tower facility

USGS Publications Warehouse

Diehl, Robert H.; Valdez, Ernest W.; Preston, Todd M.; Wellik, Mike J.; Cryan, Paul

2016-01-01

Solar power towers produce electrical energy from sunlight at an industrial scale. Little is known about the effects of this technology on flying animals and few methods exist for automatically detecting or observing wildlife at solar towers and other tall anthropogenic structures. Smoking objects are sometimes observed co-occurring with reflected, concentrated light (“solar flux”) in the airspace around solar towers, but the identity and origins of such objects can be difficult to determine. In this observational pilot study at the world’s largest solar tower facility, we assessed the efficacy of using radar, surveillance video, and insect trapping to detect and observe animals flying near the towers. During site visits in May and September 2014, we monitored the airspace surrounding towers and observed insects, birds, and bats under a variety of environmental and operational conditions. We detected and broadly differentiated animals or objects moving through the airspace generally using radar and near solar towers using several video imaging methods. Video revealed what appeared to be mostly small insects burning in the solar flux. Also, we occasionally detected birds flying in the solar flux but could not accurately identify birds to species or the types of insects and small objects composing the vast majority of smoking targets. Insect trapping on the ground was somewhat effective at sampling smaller insects around the tower, and presence and abundance of insects in the traps generally trended with radar and video observations. Traps did not tend to sample the larger insects we sometimes observed flying in the solar flux or found dead on the ground beneath the towers. Some of the methods we tested (e.g., video surveillance) could be further assessed and potentially used to automatically detect and observe flying animals in the vicinity of solar towers to advance understanding about their effects on wildlife.

Evaluating the Effectiveness of Wildlife Detection and Observation Technologies at a Solar Power Tower Facility.

PubMed

Diehl, Robert H; Valdez, Ernest W; Preston, Todd M; Wellik, Michael J; Cryan, Paul M

2016-01-01

Solar power towers produce electrical energy from sunlight at an industrial scale. Little is known about the effects of this technology on flying animals and few methods exist for automatically detecting or observing wildlife at solar towers and other tall anthropogenic structures. Smoking objects are sometimes observed co-occurring with reflected, concentrated light ("solar flux") in the airspace around solar towers, but the identity and origins of such objects can be difficult to determine. In this observational pilot study at the world's largest solar tower facility, we assessed the efficacy of using radar, surveillance video, and insect trapping to detect and observe animals flying near the towers. During site visits in May and September 2014, we monitored the airspace surrounding towers and observed insects, birds, and bats under a variety of environmental and operational conditions. We detected and broadly differentiated animals or objects moving through the airspace generally using radar and near solar towers using several video imaging methods. Video revealed what appeared to be mostly small insects burning in the solar flux. Also, we occasionally detected birds flying in the solar flux but could not accurately identify birds to species or the types of insects and small objects composing the vast majority of smoking targets. Insect trapping on the ground was somewhat effective at sampling smaller insects around the tower, and presence and abundance of insects in the traps generally trended with radar and video observations. Traps did not tend to sample the larger insects we sometimes observed flying in the solar flux or found dead on the ground beneath the towers. Some of the methods we tested (e.g., video surveillance) could be further assessed and potentially used to automatically detect and observe flying animals in the vicinity of solar towers to advance understanding about their effects on wildlife.

Evaluating the Effectiveness of Wildlife Detection and Observation Technologies at a Solar Power Tower Facility

PubMed Central

Diehl, Robert H.; Valdez, Ernest W.; Preston, Todd M.; Wellik, Michael J.; Cryan, Paul M.

2016-01-01

Solar power towers produce electrical energy from sunlight at an industrial scale. Little is known about the effects of this technology on flying animals and few methods exist for automatically detecting or observing wildlife at solar towers and other tall anthropogenic structures. Smoking objects are sometimes observed co-occurring with reflected, concentrated light (“solar flux”) in the airspace around solar towers, but the identity and origins of such objects can be difficult to determine. In this observational pilot study at the world’s largest solar tower facility, we assessed the efficacy of using radar, surveillance video, and insect trapping to detect and observe animals flying near the towers. During site visits in May and September 2014, we monitored the airspace surrounding towers and observed insects, birds, and bats under a variety of environmental and operational conditions. We detected and broadly differentiated animals or objects moving through the airspace generally using radar and near solar towers using several video imaging methods. Video revealed what appeared to be mostly small insects burning in the solar flux. Also, we occasionally detected birds flying in the solar flux but could not accurately identify birds to species or the types of insects and small objects composing the vast majority of smoking targets. Insect trapping on the ground was somewhat effective at sampling smaller insects around the tower, and presence and abundance of insects in the traps generally trended with radar and video observations. Traps did not tend to sample the larger insects we sometimes observed flying in the solar flux or found dead on the ground beneath the towers. Some of the methods we tested (e.g., video surveillance) could be further assessed and potentially used to automatically detect and observe flying animals in the vicinity of solar towers to advance understanding about their effects on wildlife. PMID:27462989

A metabolomics study of the inhibitory effect of 17-beta-estradiol on osteoclast proliferation and differentiation.

PubMed

Liu, Xiaoyan; Liu, Yanqiu; Cheng, Mengchun; Zhang, Xiaozhe; Xiao, Hongbin

2015-02-01

Estradiol is a major drug used clinically to alleviate osteoporosis, partly through inhibition of the activity of osteoclasts, which play a crucial role in bone resorption. So far, little is known about the effects of estradiol on osteoclast metabolism. In this study, ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC/MS)-based metabolomics strategy was used to investigate the metabolite response to 17β-estradiol in mouse osteoclast RAW264.7, a commonly used cell model for studying osteoporosis. Our results showed that the application of estradiol altered the levels of 27 intracellular metabolites, including lysophosphatidylcholines (LysoPCs), other lipids and amino acid derivants. The changes of all the 27 metabolites were observed in the study of estradiol induced osteoclast proliferation inhibition (1 μM estradiol applied), while the changes of only 18 metabolites were observed in the study of differentiation inhibition (0.1 μM estradiol applied). Further pathway impact analysis determined glycerophospholipid metabolism as the main potential target pathway of estradiol, which was further confirmed by LCAT (phosphatidylcholine-sterol acyltransferase) activity changes and lipid peroxidative product (MDA, methane dicarboxylic aldehyde) changes caused by estradiol. Additionally, we found that estradiol significantly decreased intracellular oxidative stress during cell proliferation but not during cell differentiation. Our study suggested that estradiol generated a highly condition-dependent influence on osteoclast metabolism.

Observations of a Greenstein effect in the O I 1302A emission of Comet Halley

NASA Astrophysics Data System (ADS)

Dymond, K. F.; Feldman, P. D.; Woods, T. N.

1989-03-01

Far-ultraviolet spectra of Comet Halley (1986 III) were obtained on February 26, 1986, 17 days after perihelion, and on March 13, 1986, 13 hr before the Giotto encounter, using an imaging spectrograph aboard a sounding rocket. A sunward-antisunward asymmetry observed in the brightness distribution of the O I 1302A emission is a result of the differential Swings effect first discussed by Greenstein (1958) for Fraunhofer structure in the solar continuum. The mean velocity of the O atoms in the coma at cometocentric radii greater than 10,000 km was 2.2 + or - 0.8 km/s based on model calculations which incorporate the Greenstein effect. This velocity is consistent with H2O as the principal source of oxygen.

A Generalized DIF Effect Variance Estimator for Measuring Unsigned Differential Test Functioning in Mixed Format Tests

ERIC Educational Resources Information Center

Penfield, Randall D.; Algina, James

2006-01-01

One approach to measuring unsigned differential test functioning is to estimate the variance of the differential item functioning (DIF) effect across the items of the test. This article proposes two estimators of the DIF effect variance for tests containing dichotomous and polytomous items. The proposed estimators are direct extensions of the…

The Effect of Special Reduction Procedures of IFU Observations from Gemini-NIFS on Dynamical Measurements of Nearby AGN

NASA Astrophysics Data System (ADS)

Pope, Crystal L.; Crenshaw, D. Michael; Fischer, Travis C.

2016-01-01

We present a preliminary analysis of the inflows and outflows in the narrow-line regions of nearby (z<0.1) AGN using observations from the Gemini-North telescope's Near-Infared Integral Field Spectrograph (NIFS). In addition to the standard reduction procedure for NIFS data cubes, these observations were treated for multiple sources of noise and artifacts from the adaptive optics observations and the NIFS instrument. This procedure included the following steps: correction of the differential atmospheric refraction, spatial resampling, low-pass Butterworth spatial filtering, removal of the "instrumental fingerprint", and the Richardson-Lucy deconvolution. We compare measurements from NIFS data cubes with and without the additional correction procedures to determine the effect of this data treatment on our scientific results.

Neuroprotective Effect of CeO2@PAA-LXW7 Against H2O2-Induced Cytotoxicity in NGF-Differentiated PC12 Cells.

PubMed

Jia, Jingjing; Zhang, Ting; Chi, Jieshan; Liu, Xiaoma; Sun, Jingjing; Xie, Qizhi; Peng, Sijia; Li, Changyan; Yi, Li

2018-06-07

CeO 2 nanoparticles (nanoceria) have been used in many studies as a powerful free radical scavenger, and LXW7, a small-molecule peptide, can specifically target the integrin αvβ3, whose neuroprotective effects have also been demonstrated. The objective of this study is to observe the neuroprotective effect and potential mechanism of CeO 2 @PAA-LXW7, a new compound that couples CeO 2 @PAA (nanoceria modified with the functional group of polyacrylic acid) with LXW7 via a series of chemical reactions, in H 2 O 2 -induced NGF-differentiated PC12 cells. We examined the effects of LXW7, CeO 2 @PAA, and CeO 2 @PAA-LXW7 on the viability of primary hippocampal neurons and found that there was no significant difference under control conditions, but increased cellular viability was observed in the case of H 2 O 2 -induced injury. We used H 2 O 2 -induced NGF-differentiated PC12 cells as the classical injury model to investigate the neuroprotective effect of CeO 2 @PAA-LXW7. In this study, LXW7, CeO 2 @PAA, and CeO 2 @PAA-LXW7 inhibit H 2 O 2 -induced oxidative stress by reducing the production of reactive oxygen species (ROS) and regulating Bax/Bcl-2, cleaved caspase-3 and mitochondrial cytochrome C (cyto C) in the apoptotic signaling pathways. We found that the levels of phosphorylation of focal adhesion kinase (FAK) and of signal transducer and activator of transcription 3 (STAT3) increased significantly in H 2 O 2 -induced NGF-differentiated PC12 cells, whereas LXW7, CeO 2 @PAA, and CeO 2 @PAA-LXW7 suppressed the increase to different degrees. Among the abovementioned changes, the inhibitory effect of CeO 2 @PAA-LXW7 on H 2 O 2 -induced changes, including the increases in the levels of p-FAK and p-STAT3, is more obvious than that of LXW7 or CeO 2 @PAA alone. In summary, these results suggest that integrin signaling participates in the regulation of apoptosis via the regulation of ROS and of the apoptosis pathway in H 2 O 2 -induced NGF-differentiated PC12 cells. LXW7, Ce

Silibinin alleviates high glucose-suppressed osteogenic differentiation of human bone marrow stromal cells via antioxidant effect and PI3K/Akt signaling.

PubMed

Ying, Xiaozhou; Chen, Xiaowei; Liu, Haixiao; Nie, Pengfei; Shui, Xiaolong; Shen, Yue; Yu, Kehe; Cheng, Shaowen

2015-10-15

High glucose is one of the possible causes for osteoporosis and fracture in diabetes mellitus. Our previous study showed that silibinin can increase osteogenic effect by stimulating osteogenic genes expression in human bone marrow stem cells (hBMSCs). However, no study has yet investigated the effect of silibinin on osteogenic differentiation of hBMSCs cultured with high glucose. The aim of this study was to evaluate the influence of high glucose on osteogenic differentiation of hBMSCs and to determine if silibinin can alleviate those effects. In this study, the hBMSCs were cultured in an osteogenic medium with physiological (normal glucose, NG, 5.5mM) or diabetic (high glucose, HG, 30mM). The effects of silibinin on HG-induced osteogenic differentiation were evaluated by alkaline phosphatas (ALP) activity assay, Von Kossa staining and real time-polymerase chain reaction. HG-induced oxidative damage was also assessed. Western blot were performed to examine the role of PI3K/Akt pathway. We demonstrated that HG suppressed osteogenic differentiation of hBMSCs, manifested by a decrease in expression of osteogenic markers and an increase of oxidative damage markers including reactive oxygen species and lipid peroxide (MDA). Remarkably, all of the observed oxidative damage and osteogenic dysfunction induced by HG were inhibited by silibinin. Furthermore, the PI3K/Akt pathway was activated by silibinin. These results demonstrate that silibinin may attenuate HG-mediated hBMSCs dysfunction through antioxidant effect and modulation of PI3K/Akt pathway, suggesting that silibinin may be a superior drug candidate for the treatment of diabetes related bone diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

Differential collision cross-sections for atomic oxygen

NASA Technical Reports Server (NTRS)

Torr, Douglas G.

1991-01-01

Differential collision cross-sections of O on N2 and other gases were measured to understand vehicle-environmental contamination effects in orbit. The following subject areas are also covered: groundbased scientific observations of rocket releases during NICARE-1; data compression study for the UVI; science priorities for UV imaging in the mid-1990's; and assessment of optimizations possible in UV imaging systems.

On polarimetric radar signatures of deep convection for model evaluation: columns of specific differential phase observed during MC3E.

PubMed

van Lier-Walqui, Marcus; Fridlind, Ann M; Ackerman, Andrew S; Collis, Scott; Helmus, Jonathan; MacGorman, Donald R; North, Kirk; Kollias, Pavlos; Posselt, Derek J

2016-02-01

The representation of deep convection in general circulation models is in part informed by cloud-resolving models (CRMs) that function at higher spatial and temporal resolution; however, recent studies have shown that CRMs often fail at capturing the details of deep convection updrafts. With the goal of providing constraint on CRM simulation of deep convection updrafts, ground-based remote-sensing observations are analyzed and statistically correlated for four deep convection events observed during the Midlatitude Continental Convective Clouds Experiment (MC3E). Since positive values of specific differential phase ( K DP ) observed above the melting level are associated with deep convection updraft cells, so-called " K DP columns" are analyzed using two scanning polarimetric radars in Oklahoma: the National Weather Service Vance WSR-88D (KVNX) and the Department of Energy C-band Scanning Atmospheric Radiation Measurement (ARM) Precipitation Radar (C-SAPR). KVNX and C-SAPR K DP volumes and columns are then statistically correlated with vertical winds retrieved via multi-Doppler wind analysis, lightning flash activity derived from the Oklahoma Lightning Mapping Array, and KVNX differential reflectivity ( Z DR ). Results indicate strong correlations of K DP volume above the melting level with updraft mass flux, lightning flash activity, and intense rainfall. Analysis of K DP columns reveals signatures of changing updraft properties from one storm event to another as well as during event evolution. Comparison of Z DR to K DP shows commonalities in information content of each, as well as potential problems with Z DR associated with observational artifacts.

Differentiation of Rat bone marrow Mesenchymal stem cells into Adipocytes and Cardiomyocytes after treatment with platelet lysate.

PubMed

Homayouni Moghadam, Farshad; Tayebi, Tahereh; Barzegar, Kazem

2016-01-01

Mesenchymal stem cells (MSCs) are multipotential cells and their therapeutic potency is under intense investigation. Studying the effect of different induction factors on MSCs could increase our knowledge about the differentiation potency of these cells. One of the most important sources of these factors in mammalian body is platelet. Platelet lysate (PL) contains many growth factors and therefore, it can be used as a differentiation inducer. In the present study, the effect of PL on differentiation of rat bone marrow MSCs into cardiomyocytes was studied. To study the differentiation-inducing effect of PL, MSCs were treated with 2.5, 5 and 10% PL. Early results of this study showed that PL in high concentrations (10%) induces adipogenic differentiation of MSCs. Therefore, to evaluate differentiation to cardiomyocytes, MSCs were cultured in media containing lower levels of PL (2.5% and 5%) and then cardiomyogenic differentiation was induced by treatment with 5-azacytidine. Differentiation of MSCs was evaluated using direct observation of beating cells, immunostaining and real-time PCR techniques. The results of qPCR showed that treatment with PL alone increased the expression of cardiac alpha actinin (CAA) being predictable by earlier observation of beating cells in PL-treated groups. The results of staining assays against cardiac alpha actinin also showed that there were stained cells in PL-treated groups. The results of the present study showed that PL is a powerful induction factor for differentiation of MSCs into different cell lines such as cardiomyocytes and adipocytes.

Promotive Effect of Zinc Ions on the Vitality, Migration, and Osteogenic Differentiation of Human Dental Pulp Cells.

PubMed

An, Shaofeng; Gong, Qimei; Huang, Yihua

2017-01-01

Zinc is an essential trace element for proper cellular function and bone formation. However, its exact role in the osteogenic differentiation of human dental pulp cells (hDPCs) has not been fully clarified before. Here, we speculated that zinc may be effective to regulate their growth and osteogenic differentiation properties. To test this hypothesis, different concentrations (1 × 10 -5 , 4 × 10 -5 , and 8 × 10 -5  M) of zinc ions (Zn 2+ ) were added to the basic growth culture medium and osteogenic inductive medium. Cell viability and migration were measured by cell counting kit-8 (CCK-8) and transwell migration assay in the basic growth culture medium, respectively. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the gene expression levels of selective osteogenic differentiation markers and zinc transporters. Alkaline phosphatase (ALP) activity analysis and alizarin red S staining were used to investigate the mineralization of hDPCs. Exposure of hDPCs to Zn 2+ stimulated their viability and migration capacity in a dose- and time-dependent manner. RT-qPCR assay revealed elevated expression levels of osteogenic differentiation-related genes and zinc transporters genes in various degrees. ALP activity was also increased with elevated Zn 2+ concentrations and extended culture periods, but enhanced matrix nodules formation were observed only in 4 × 10 -5 and 8 × 10 -5  M Zn 2+ groups. These findings suggest that specific concentrations of Zn 2+ could potentiate the vitality, migration, and osteogenic differentiation of hDPCs. We may combine optimum zinc element into pulp capping materials to improve their biological performance.

Identification of Differentially Methylated Sites with Weak Methylation Effects

PubMed Central

Tran, Hong; Zhu, Hongxiao; Wu, Xiaowei; Kim, Gunjune; Clarke, Christopher R.; Larose, Hailey; Haak, David C.; Westwood, James H.; Zhang, Liqing

2018-01-01

Deoxyribonucleic acid (DNA) methylation is an epigenetic alteration crucial for regulating stress responses. Identifying large-scale DNA methylation at single nucleotide resolution is made possible by whole genome bisulfite sequencing. An essential task following the generation of bisulfite sequencing data is to detect differentially methylated cytosines (DMCs) among treatments. Most statistical methods for DMC detection do not consider the dependency of methylation patterns across the genome, thus possibly inflating type I error. Furthermore, small sample sizes and weak methylation effects among different phenotype categories make it difficult for these statistical methods to accurately detect DMCs. To address these issues, the wavelet-based functional mixed model (WFMM) was introduced to detect DMCs. To further examine the performance of WFMM in detecting weak differential methylation events, we used both simulated and empirical data and compare WFMM performance to a popular DMC detection tool methylKit. Analyses of simulated data that replicated the effects of the herbicide glyphosate on DNA methylation in Arabidopsis thaliana show that WFMM results in higher sensitivity and specificity in detecting DMCs compared to methylKit, especially when the methylation differences among phenotype groups are small. Moreover, the performance of WFMM is robust with respect to small sample sizes, making it particularly attractive considering the current high costs of bisulfite sequencing. Analysis of empirical Arabidopsis thaliana data under varying glyphosate dosages, and the analysis of monozygotic (MZ) twins who have different pain sensitivities—both datasets have weak methylation effects of <1%—show that WFMM can identify more relevant DMCs related to the phenotype of interest than methylKit. Differentially methylated regions (DMRs) are genomic regions with different DNA methylation status across biological samples. DMRs and DMCs are essentially the same concepts, with

Differential Effects of Small Molecule WNT Agonists on the Multilineage Differentiation Capacity of Human Mesenchymal Stem Cells.

PubMed

Narcisi, Roberto; Arikan, Ozan H; Lehmann, Johannes; Ten Berge, Derk; van Osch, Gerjo J V M

2016-11-01

Human bone marrow-derived mesenchymal stem cells (MSCs) are promising candidates for cell-based therapies, but loss of expansion and differentiation potential in vitro limits their applicability. Recently we showed that WNT3A protein promoted MSC proliferation and enhanced their chondrogenic potential, while simultaneously suppressing the propensity of the cartilage to undergo hypertrophic maturation. Since WNT3A protein is costly and rapidly loses its activity in culture, we investigated the possibility of replacing it with cheaper commercially available WNT agonists, specifically lithium chloride (LiCl), CHIR99021 (CHIR), SKL2001, and AMBMP. Of these, we found that only CHIR and LiCl stimulated MSC proliferation. Moreover, CHIR enhanced the chondrogenic capacity of MSCs, whereas LiCl predominantly increased the osteo- and adipogenic capacity. The different WNT agonists also differentially impacted the surface marker profile of the MSCs, possibly explaining the observed differences. Moreover, CHIR suppressed the hypertrophic propensity of the MSC-derived cartilage after in vivo implantation to an extent approaching that of WNT3A protein. These results indicate that CHIR may be a promising alternative for WNT3A protein for certain applications of human bone marrow-derived MSCs.

Differentiating the Differentiation Models: A Comparison of the Retrieving Effectively from Memory Model (REM) and the Subjective Likelihood Model (SLiM)

ERIC Educational Resources Information Center

Criss, Amy H.; McClelland, James L.

2006-01-01

The subjective likelihood model [SLiM; McClelland, J. L., & Chappell, M. (1998). Familiarity breeds differentiation: a subjective-likelihood approach to the effects of experience in recognition memory. "Psychological Review," 105(4), 734-760.] and the retrieving effectively from memory model [REM; Shiffrin, R. M., & Steyvers, M. (1997). A model…

Alternating current electric fields of varying frequencies: effects on proliferation and differentiation of porcine neural progenitor cells.

PubMed

Lim, Ji-Hey; McCullen, Seth D; Piedrahita, Jorge A; Loboa, Elizabeth G; Olby, Natasha J

2013-10-01

Application of sinusoidal electric fields (EFs) has been observed to affect cellular processes, including alignment, proliferation, and differentiation. In the present study, we applied low-frequency alternating current (AC) EFs to porcine neural progenitor cells (pNPCs) and investigated the effects on cell patterning, proliferation, and differentiation. pNPCs were grown directly on interdigitated electrodes (IDEs) localizing the EFs to a region accessible visually for fluorescence-based assays. Cultures of pNPCs were exposed to EFs (1 V/cm) of 1 Hz, 10 Hz, and 50 Hz for 3, 7, and 14 days and compared to control cultures. Immunocytochemistry was performed to evaluate the expression of neural markers. pNPCs grew uniformly with no evidence of alignment to the EFs and no change in cell numbers when compared with controls. Nestin expression was shown in all groups at 3 and 7 days, but not at 14 days. NG2 expression was low in all groups. Co-expression of glial fibrillary acidic protein (GFAP) and TUJ1 was significantly higher in the cultures exposed to 10- and 50-Hz EFs than the controls. In summary, sinusoidal AC EFs via IDEs did not alter the alignment and proliferation of pNPCs, but higher frequency stimulation appeared to delay differentiation into mature astrocytes.

[Proliferation and morphological differentiation of neurblastoma cells in cultured under the effect of avermectins].

PubMed

Miakisheva, S N; Kostenko, M A; Driniaev, V A; Mosin, V A

2001-01-01

The effect of natural avermectin complex (Aversectin C) and Abamectin on the processes of proliferation and morphological differentiation of the neural cells was studied using N1E-115 murine neuroblastoma cells (clone C-1300) as a model. Aversectin C in concentrations 10(-7)-10(-8) was shown to induce morphological differentiation of cultured nervous cells. Treatment with Abamectin resulted in the changes of proliferation pattern of the cells. Morphological differentiation of the cultured nervous cells treated with Aversectin C was associated with electrophysiological one.

Effects of strontium on proliferation and differentiation of rat bone marrow mesenchymal stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yunfeng; Li, Jihua; Zhu, Songsong

Highlights: Black-Right-Pointing-Pointer Strontium ranelate (SrR) inhibits proliferation of BMMSCs. Black-Right-Pointing-Pointer SrR increases osteoblastic but decreases adipocytic differentiation of BMMSCs. Black-Right-Pointing-Pointer SrR increases expression of Runx2, BSP and OCN by BMMSCs in osteogenic medium. Black-Right-Pointing-Pointer SrR decreases expression of PPAR{gamma}, aP2/ALBP and LPL by BMMSCs in adipogenic medium. -- Abstract: Strontium ranelate (SrR) was an effective anti-osteoporotic drug to increase bone formation and decrease bone resorption. However, reports about the effect of SR on osteoblastic and adipocytic differentiation from bone marrow mesenchymal stem cells (BMMSCs) are limited. The purpose of this study is to evaluate whether SrR affects the ability ofmore » BMMSCs to differentiate into osteoblasts or adipocytes. Rat BMMSCs were identified by flow cytometry and exposed to SR (0.1 and 1.0 mM Sr{sup 2+}) under osteogenic or adipogenic medium for 1 and 2 weeks. The proliferation and differentiation of BMMSCs were analyzed by MTT, alkaline phosphatase (ALP), Oil red O staining, quantitative real-time RT-PCR and Western blot assays. SrR significantly inhibited the proliferation, increased osteoblastic but decreased adipocytic differentiation of rat BMMSCs dose-dependently. In osteogenic medium, SrR increased the expression of ALP, the mRNA levels of Cbfa1/Runx2, bone sialoprotein, and osteocalcin by RT-PCR, and the protein levels of Cbfa1/Runx2 by Western blot. In adipogenic medium, SrR decreased the mRNA levels of PPAR{gamma}2, adipocyte lipid-binding protein 2 (aP2/ALBP), and lipoprotein lipase (LPL) by RT-PCR, and the protein expression of PPAR{gamma} in Western blot analysis. These results indicated that the effects of SrR to promote osteoblastic but inhibit adipocytic differentiation of BMMSCs might contribute to its effect on osteoporosis treatment.« less

Negative differential resistance observation in complex convoluted fullerene junctions

NASA Astrophysics Data System (ADS)

Kaur, Milanpreet; Sawhney, Ravinder Singh; Engles, Derick

2018-04-01

In this work, we simulated the smallest fullerene molecule, C20 in a two-probe device model with gold electrodes. The gold electrodes comprised of (011) miller planes were carved to construct the novel geometry based four unique shapes, which were strung to fullerene molecules through mechanically controlled break junction techniques. The organized devices were later scrutinized using non-equilibrium Green's function based on the density functional theory to calculate their molecular orbitals, energy levels, charge transfers, and electrical parameters. After intense scrutiny, we concluded that five-edged and six-edged devices have the lowest and highest current-conductance values, which result from their electrode-dominating and electrode-subsidiary effects, respectively. However, an interesting observation was that the three-edged and four-edged electrodes functioned as semi-metallic in nature, allowing the C20 molecule to demonstrate its performance with the complementary effect of these electrodes in the electron conduction process of a two-probe device.

Multiple-Bit Differential Detection of OQPSK

NASA Technical Reports Server (NTRS)

Simon, Marvin

2005-01-01

A multiple-bit differential-detection method has been proposed for the reception of radio signals modulated with offset quadrature phase-shift keying (offset QPSK or OQPSK). The method is also applicable to other spectrally efficient offset quadrature modulations. This method is based partly on the same principles as those of a multiple-symbol differential-detection method for M-ary QPSK, which includes QPSK (that is, non-offset QPSK) as a special case. That method was introduced more than a decade ago by the author of the present method as a means of improving performance relative to a traditional (two-symbol observation) differential-detection scheme. Instead of symbol-by-symbol detection, both that method and the present one are based on a concept of maximum-likelihood sequence estimation (MLSE). As applied to the modulations in question, MLSE involves consideration of (1) all possible binary data sequences that could have been received during an observation time of some number, N, of symbol periods and (2) selection of the sequence that yields the best match to the noise-corrupted signal received during that time. The performance of the prior method was shown to range from that of traditional differential detection for short observation times (small N) to that of ideal coherent detection (with differential encoding) for long observation times (large N).

Differential effects of phasic and tonic alerting on the efficiency of executive attention.

PubMed

Asanowicz, Dariusz; Marzecová, Anna

2017-05-01

The study examined how alerting and executive attention interact in a task involving conflict resolution. We proposed a tentative scenario in which an initial exogenous phasic alerting phase is followed by an endogenous tonic alerting phase, and hypothesized that these two processes may have distinct effects on conflict resolution. Phasic alerting was expected to increase the conflict, whereas tonic alerting was expected to decrease the conflict. Three experiments were conducted using different variants of the flanker task with visual alerting cues and varied cue-target intervals (SOA), to differentiate between effects of phasic alerting (short SOA) and tonic alerting (long SOA). The results showed that phasic alerting consistently decreased the efficiency of conflict resolution indexed by response time and accuracy, whereas tonic alerting increased the accuracy of conflict resolution, but at a cost in the speed of processing the conflict. The third experiment additionally showed that the effects of phasic alerting may be modulated by the psychophysical strength of alerting cues. Discussed are possible mechanisms that could account for the observed interactions between alerting and conflict resolution, as well as some discrepancies between the current and previous studies. Copyright © 2017 Elsevier B.V. All rights reserved.

The effects of diazinon and cypermethrin on the differentiation of neuronal and glial cell lines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flaskos, J.; Harris, W.; Sachana, M.

2007-03-15

Diazinon and cypermethrin are pesticides extensively used in sheep dipping. Diazinon is a known anti-cholinesterase, but there is limited information regarding its molecular mechanism of action. This paper describes the effects of diazinon and cypermethrin at a morphological and molecular level on differentiating mouse N2a neuroblastoma and rat C6 glioma cell lines. Concentrations up to 10 {mu}M of both compounds and their mixture had no effect on the viability of either cell line, as determined by methyl blue tetrazolium reduction and total protein assays. Microscopic analysis revealed that 1 {mu}M and 10 {mu}M diazinon but not cypermethrin inhibited the outgrowthmore » of axon-like processes in N2a cells after a 24-h exposure but neither compound affected process outgrowth by differentiating C6 cells at these concentrations. Under these conditions, 10 {mu}M diazinon inhibited AChE slightly compared to the control after a 4-h exposure but not after 24 h. Western blotting analysis showed that morphological changes were associated with reduced cross-reactivity with antibodies that recognize the neurofilament heavy chain (NFH), microtubule associated protein MAP 1B and HSP-70 compared to control cell extracts, whereas reactivity with anti-{alpha}-tubulin antibodies was unchanged. Aggregation of NFH was observed in cell bodies of diazinon-treated N2a cells, as determined by indirect immunofluorescence staining. These data demonstrate that diazinon specifically targets neurite outgrowth in neuronal cells and that this effect is associated with disruption of axonal cytoskeleton proteins, whereas cypermethrin has no effect on the same parameters.« less

Effect Size Measures for Differential Item Functioning in a Multidimensional IRT Model

ERIC Educational Resources Information Center

Suh, Youngsuk

2016-01-01

This study adapted an effect size measure used for studying differential item functioning (DIF) in unidimensional tests and extended the measure to multidimensional tests. Two effect size measures were considered in a multidimensional item response theory model: signed weighted P-difference and unsigned weighted P-difference. The performance of…

A Differential Analysis of Effectiveness in Middle and Low Socioeconomic Status Schools

ERIC Educational Resources Information Center

Teddlie, Charles; Stringfield, Samuel

2017-01-01

A major focus of the Louisiana School Effectiveness Study has been the search for characteristics of exemplary schooling in varied economic contexts. In this paper differential results of analyses of effective, typical, and ineffective schools in middle and low socioeconomic neighborhoods are presented. Implications for practitioners and for…

Effective Differentiation: A Guide for Teachers and Leaders. Q&A for Carol A. Tomlinson, Ed.D. REL Mid-Atlantic Educator Effectiveness Webinar Series

ERIC Educational Resources Information Center

Regional Educational Laboratory Mid-Atlantic, 2015

2015-01-01

In this webinar, Dr. Carol Tomlinson of the University of Virginia presented the research base supporting the practice of differentiation and described the characteristics of effective differentiation. She led a discussion of how quality preparation can build and strengthen teachers' knowledge and skills in implementing differentiated instruction…

Differential DNases are selectively used in neuronal apoptosis depending on the differentiation state.

PubMed

Shiokawa, D; Tanuma, S

2004-10-01

In this study, we investigate the roles of two apoptotic endonucleases, CAD and DNase gamma, in neuronal apoptosis. High expression of CAD, but not DNase gamma, is detected in proliferating N1E-115 neuroblastoma cells, and apoptotic DNA fragmentation induced by staurosporine under proliferating conditions is abolished by the expression of a caspase-resistant form of ICAD. After the induction of neuronal differentiation, CAD disappearance and the induction of DNase gamma occur simultaneously in N1E-115 cells. Apoptotic DNA fragmentation that occurs under differentiating conditions is suppressed by the downregulation of DNase gamma caused by its antisense RNA. The induction of DNase gamma is also observed during neuronal differentiation of PC12 cells, and apoptotic DNA fragmentation induced by NGF deprivation is inhibited by the antisense-mediated downregulation of DNase gamma. These observations suggest that DNA fragmentation in neuronal apoptosis is catalyzed by either CAD or DNase gamma depending on the differentiation state. Furthermore, DNase gamma is suggested to be involved in naturally occurring apoptosis in developing nervous systems.

Effect of sertraline on proliferation and neurogenic differentiation of human adipose-derived stem cells

PubMed Central

Razavi, Shahnaz; Jahromi, Maliheh; Amirpour, Nushin; Khosravizadeh, Zahra

2014-01-01

Background: Antidepressant drugs are commonly employed for anxiety and mood disorders. Sertraline is extensively used as antidepressant in clinic. In addition, adipose tissue represents an abundant and accessible source of adult stem cells with the ability to differentiate in to multiple lineages. Therefore, human adipose-derived stem cells (hADSCs) may be useful for autologous transplantation. Materials and Methods: In the present study, we assessed the effect of antidepressant drug Sertraline on the proliferation and neurogenic differentiation of hADSCs using MTT assay and immunofluorescence technique respectively. Results: MTT assay analysis showed that 0.5 μM Sertraline significantly increased the proliferation rate of hADSCs induced cells (P < 0.05), while immunofluorescent staining indicated that Sertraline treatment during neurogenic differentiation could be decreased the percentage of glial fibrillary acidic protein and Nestin-positive cells, but did not significantly effect on the percentage of MAP2 positive cells. Conclusion: Overall, our data show that Sertraline can be promoting proliferation rate during neurogenic differentiation of hADSCs after 6 days post-induction, while Sertraline inhibits gliogenesis of induced hADSCs. PMID:24800186

Effect of molecular weight and concentration of hyaluronan on cell proliferation and osteogenic differentiation in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Ningbo, E-mail: curl-zhao@163.com; Wang, Xin, E-mail: 394041230@qq.com; Qin, Lei, E-mail: qinlei30@126.com

Hyaluronan (HA), the simplest glycosaminoglycan and a major component of the extracellular matrix, exists in various tissues. It is involved in some critical biological procedures, including cellular signaling, cell adhesion and proliferation, and cell differentiation. The effect of molecular weight (MW) and concentration of HA on cell proliferation and differentiation was controversial. In this study, we investigated the effect of MW and concentration of HA on the proliferation and osteogenic differentiation of rabbit bone marrow-derived stem cells in vitro. Results showed that high MW HA decreased the cell adhesion rate in a concentration-dependant manner. The cell adhesion rate was decreased bymore » increasing MW of HA. Cell proliferation was significantly enhanced by low MW HA (P < 0.05). The factorial analysis indicated that MW and concentration had an interactive effect on the cell adhesion rate and cell proliferation (P < 0.05). High MW HA increased the mRNA expressions of ALP, RUNX-2 and OCN. The higher the MW was, the higher the mRNA expressions were. The factorial analysis indicated that MW and concentration had an interactive effect on ALP mRNA expression (P < 0.05). HA of higher MW and higher concentration promoted bone formation. These findings provide some useful information in understanding the mechanism underlying the effect of MW and concentration of HA on cell proliferation and differentiation. - Highlights: • Effect of hyaluronan on cell proliferation and differentiation is evaluated in vitro. • Hyaluronan of low molecular weight increases cell proliferation. • Hyaluronan of high molecular weight promotes cell osteogenic differentiation. • Molecular weight and concentration of hyaluronan show interactive effect.« less

Differentiated Instruction at Work. Reinforcing the Art of Classroom Observation through the Creation of a Checklist for Beginning and Pre-Service Teachers

ERIC Educational Resources Information Center

Subban, Pearl; Round, Penny

2015-01-01

Professional experience is viewed as integral to shaping philosophy and acquiring skills in the area of classroom teaching. Classrooms are complex places, with educators implementing differentiated strategies to cater for student diversity. Pre-service teachers who observe these lessons often miss the intuitive practices, as there is much to…

High and Low Molecular Weight Hyaluronic Acid Differentially Regulate Human Fibrocyte Differentiation

PubMed Central

Maharjan, Anu S.; Pilling, Darrell; Gomer, Richard H.

2011-01-01

Background Following tissue injury, monocytes can enter the tissue and differentiate into fibroblast-like cells called fibrocytes, but little is known about what regulates this differentiation. Extracellular matrix contains high molecular weight hyaluronic acid (HMWHA; ∼2×106 Da). During injury, HMWHA breaks down to low molecular weight hyaluronic acid (LMWHA; ∼0.8–8×105 Da). Methods and Findings In this report, we show that HMWHA potentiates the differentiation of human monocytes into fibrocytes, while LMWHA inhibits fibrocyte differentiation. Digestion of HMWHA with hyaluronidase produces small hyaluronic acid fragments, and these fragments inhibit fibrocyte differentiation. Monocytes internalize HMWHA and LMWHA equally well, suggesting that the opposing effects on fibrocyte differentiation are not due to differential internalization of HMWHA or LMWHA. Adding HMWHA to PBMC does not appear to affect the levels of the hyaluronic acid receptor CD44, whereas adding LMWHA decreases CD44 levels. The addition of anti-CD44 antibodies potentiates fibrocyte differentiation, suggesting that CD44 mediates at least some of the effect of hyaluronic acid on fibrocyte differentiation. The fibrocyte differentiation-inhibiting factor serum amyloid P (SAP) inhibits HMWHA-induced fibrocyte differentiation and potentiates LMWHA-induced inhibition. Conversely, LMWHA inhibits the ability of HMWHA, interleukin-4 (IL-4), or interleukin-13 (IL-13) to promote fibrocyte differentiation. Conclusions We hypothesize that hyaluronic acid signals at least in part through CD44 to regulate fibrocyte differentiation, with a dominance hierarchy of SAP>LMWHA≥HMWHA>IL-4 or IL-13. PMID:22022512

Differentiated effects of deep brain stimulation and medication on somatosensory processing in Parkinson's disease.

PubMed

Sridharan, Kousik Sarathy; Højlund, Andreas; Johnsen, Erik Lisbjerg; Sunde, Niels Aagaard; Johansen, Lars Gottfried; Beniczky, Sándor; Østergaard, Karen

2017-07-01

Deep brain stimulation (DBS) and dopaminergic medication effectively alleviate the motor symptoms in Parkinson's disease (PD) patients, but their effects on the sensory symptoms of PD are still not well understood. To explore early somatosensory processing in PD, we recorded magnetoencephalography (MEG) from thirteen DBS-treated PD patients and ten healthy controls during median nerve stimulation. PD patients were measured during DBS-treated, untreated and dopaminergic-medicated states. We focused on early cortical somatosensory processing as indexed by N20m, induced gamma augmentation (31-45Hz and 55-100Hz) and induced beta suppression (13-30Hz). PD patients' motor symptoms were assessed by UPDRS-III. Using Bayesian statistics, we found positive evidence for differentiated effects of treatments on the induced gamma augmentation (31-45Hz) with highest gamma in the dopaminergic-medicated state and lowest in the DBS-treated and untreated states. In contrast, UPDRS-III scores showed beneficial effects of both DBS and dopaminergic medication on the patients' motor symptoms. Furthermore, treatments did not affect the amplitude of N20m. Our results suggest differentiated effects of DBS and dopaminergic medication on cortical somatosensory processing in PD patients despite consistent ameliorating effects of both treatments on PD motor symptoms. The differentiated effect suggests differences in the effect mechanisms of the two treatments. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Platelet-Released Growth Factors Induce Differentiation of Primary Keratinocytes

PubMed Central

Tohidnezhad, Mersedeh; Lammel, Justus; Lippross, Sebastian; Behrendt, Peter; Klüter, Tim; Pufe, Thomas; Jahr, Holger; Cremer, Jochen; Rademacher, Franziska; Gläser, Regine; Harder, Jürgen

2017-01-01

Autologous thrombocyte concentrate lysates, for example, platelet-released growth factors, (PRGFs) or their clinically related formulations (e.g., Vivostat PRF®) came recently into the physicians' focus as they revealed promising effects in regenerative and reparative medicine such as the support of healing of chronic wounds. To elucidate the underlying mechanisms, we analyzed the influence of PRGF and Vivostat PRF on human keratinocyte differentiation in vitro and on epidermal differentiation status of skin wounds in vivo. Therefore, we investigated the expression of early (keratin 1 and keratin 10) and late (transglutaminase-1 and involucrin) differentiation markers. PRGF treatment of primary human keratinocytes decreased keratin 1 and keratin 10 gene expression but induced involucrin and transglutaminase-1 gene expression in an epidermal growth factor receptor- (EGFR-) dependent manner. In concordance with these results, microscopic analyses revealed that PRGF-treated human keratinocytes displayed morphological features typical of keratinocytes undergoing terminal differentiation. In vivo treatment of artificial human wounds with Vivostat PRF revealed a significant induction of involucrin and transglutaminase-1 gene expression. Together, our results indicate that PRGF and Vivostat PRF induce terminal differentiation of primary human keratinocytes. This potential mechanism may contribute to the observed beneficial effects in the treatment of hard-to-heal wounds with autologous thrombocyte concentrate lysates in vivo. PMID:28808357

Physalis angulata induces in vitro differentiation of murine bone marrow cells into macrophages.

PubMed

da Silva, Bruno José Martins; Rodrigues, Ana Paula D; Farias, Luis Henrique S; Hage, Amanda Anastácia P; Do Nascimento, Jose Luiz M; Silva, Edilene O

2014-10-03

The bone marrow is a hematopoietic tissue that, in the presence of cytokines and growth factors, generates all of the circulating blood cells. These cells are important for protecting the organism against pathogens and for establishing an effective immune response. Previous studies have shown immunomodulatory effects of different products isolated from plant extracts. This study aimed to evaluate the immunomodulatory properties of aqueous Physalis angulata (AEPa) extract on the differentiation of bone marrow cells. Increased cellular area, higher spreading ability and several cytoplasmatic projections were observed in the treated cells, using optical microscopy, suggesting cell differentiation. Furthermore, AEPa did not promote the proliferation of lymphocytes and polymorphonuclear leukocytes, however promotes increased the number of macrophages in the culture. The ultrastructural analysis by Transmission Electron Microscopy of treated cells showed spreading ability, high number of cytoplasmatic projections and increase of autophagic vacuoles. Moreover, a high level of LC3b expression by treated cells was detected by flow cytometry, suggesting an autophagic process. Cell surface expression of F4/80 and CD11b also indicated that AEPa may stimulate differentiation of bone marrow cells mainly into macrophages. In addition, AEPa did not differentiate cells into dendritic cells, as assessed by CD11c analysis. Furthermore, no cytotoxic effects were observed in the cells treated with AEPa. Results demonstrate that AEPa promotes the differentiation of bone marrow cells, particularly into macrophages and may hold promise as an immunomodulating agent.

Physalis angulata induces in vitro differentiation of murine bone marrow cells into macrophages

PubMed Central

2014-01-01

Background The bone marrow is a hematopoietic tissue that, in the presence of cytokines and growth factors, generates all of the circulating blood cells. These cells are important for protecting the organism against pathogens and for establishing an effective immune response. Previous studies have shown immunomodulatory effects of different products isolated from plant extracts. This study aimed to evaluate the immunomodulatory properties of aqueous Physalis angulata (AEPa) extract on the differentiation of bone marrow cells. Results Increased cellular area, higher spreading ability and several cytoplasmatic projections were observed in the treated cells, using optical microscopy, suggesting cell differentiation. Furthermore, AEPa did not promote the proliferation of lymphocytes and polymorphonuclear leukocytes, however promotes increased the number of macrophages in the culture. The ultrastructural analysis by Transmission Electron Microscopy of treated cells showed spreading ability, high number of cytoplasmatic projections and increase of autophagic vacuoles. Moreover, a high level of LC3b expression by treated cells was detected by flow cytometry, suggesting an autophagic process. Cell surface expression of F4/80 and CD11b also indicated that AEPa may stimulate differentiation of bone marrow cells mainly into macrophages. In addition, AEPa did not differentiate cells into dendritic cells, as assessed by CD11c analysis. Furthermore, no cytotoxic effects were observed in the cells treated with AEPa. Conclusion Results demonstrate that AEPa promotes the differentiation of bone marrow cells, particularly into macrophages and may hold promise as an immunomodulating agent. PMID:25281406

Effect of amorphous silica nanoparticles on in vitro RANKL-induced osteoclast differentiation in murine macrophages

NASA Astrophysics Data System (ADS)

Nabeshi, Hiromi; Yoshikawa, Tomoaki; Akase, Takanori; Yoshida, Tokuyuki; Tochigi, Saeko; Hirai, Toshiro; Uji, Miyuki; Ichihashi, Ko-Ichi; Yamashita, Takuya; Higashisaka, Kazuma; Morishita, Yuki; Nagano, Kazuya; Abe, Yasuhiro; Kamada, Haruhiko; Tsunoda, Shin-Ichi; Itoh, Norio; Yoshioka, Yasuo; Tsutsumi, Yasuo

2011-07-01

Amorphous silica nanoparticles (nSP) have been used as a polishing agent and/or as a remineralization promoter for teeth in the oral care field. The present study investigates the effects of nSP on osteoclast differentiation and the relationship between particle size and these effects. Our results revealed that nSP exerted higher cytotoxicity in macrophage cells compared with submicron-sized silica particles. However, tartrate-resistant acid phosphatase (TRAP) activity and the number of osteoclast cells (TRAP-positive multinucleated cells) were not changed by nSP treatment in the presence of receptor activator of nuclear factor κB ligand (RANKL) at doses that did not induce cytotoxicity by silica particles. These results indicated that nSP did not cause differentiation of osteoclasts. Collectively, the results suggested that nanosilica exerts no effect on RANKL-induced osteoclast differentiation of RAW264.7 cells, although a detailed mechanistic examination of the nSP70-mediated cytotoxic effect is needed.

X-chromosome dosage as a modulator of pluripotency, signalling and differentiation?

PubMed

Schulz, Edda G

2017-11-05

Already during early embryogenesis, before sex-specific hormone production is initiated, sex differences in embryonic development have been observed in several mammalian species. Typically, female embryos develop more slowly than their male siblings. A similar phenotype has recently been described in differentiating murine embryonic stem cells, where a double dose of the X-chromosome halts differentiation until dosage-compensation has been achieved through X-chromosome inactivation. On the molecular level, several processes associated with early differentiation of embryonic stem cells have been found to be affected by X-chromosome dosage, such as the transcriptional state of the pluripotency network, the activity pattern of several signal transduction pathways and global levels of DNA-methylation. This review provides an overview of the sex differences described in embryonic stem cells from mice and discusses a series of X-linked genes that are associated with pluripotency, signalling and differentiation and their potential involvement in mediating the observed X-dosage-dependent effects.This article is part of the themed issue 'X-chromosome inactivation: a tribute to Mary Lyon'. © 2017 The Author(s).

Effect of autogenous and fresh-frozen bone grafts on osteoblast differentiation.

PubMed

Ferraz, E P; Xavier, S P; Azevedo, F G; de Oliveira, F S; Beloti, M M; Rosa, A L

2015-01-01

Fresh-frozen bone allograft (FFBA) is an alternative to autogenous bone (AB) for reconstructing maxillary bone. Despite the promising clinical results, cell responses to FFBA and AB were not evaluated. Thus, our aim was to compare cells harvested from maxillary reconstructed sites with either AB or FFBA in terms of osteoblast differentiation and to evaluate the effect of culturing cells in contact with FFBA. Cells harvested from three patients submitted to bilateral maxillary reconstruction with AB and FFBA were cultured to evaluate: proliferation, alkaline phosphatase activity, extracellular matrix mineralization and gene expression of osteoblastic markers. The effect of FFBA on osteoblast differentiation was studied by culturing cells harvested from AB in contact with FFBA and evaluating the same parameters. Data were compared using either two-way ANOVA followed by Tukey-b test or Student's t test (p≤0.05). Cell proliferation was higher in cultures from AB grafted sites and extracellular matrix mineralization was higher in cultures derived from FFBA grafted sites. The gene expression of alkaline phosphatase, RUNX2, bone sialoprotein and osteocalcin was higher in cells derived from FFBA compared with cells from AB grafted sites. However, the exposure of cells derived from AB to FFBA particles did not have any remarkable effect on osteoblast differentiation. These results indicate the higher osteogenic activity of cells derived from FFBA compared with AB reconstructed sites, offering an explanation at cellular level of why FFBA could be a suitable alternative to AB for reconstructing maxillary bone defects. Copyright © 2014 Elsevier Ltd. All rights reserved.

Differential neurogenic effects of casein-derived opioid peptides on neuronal stem cells: implications for redox-based epigenetic changes.

PubMed

Trivedi, Malav; Zhang, Yiting; Lopez-Toledano, Miguel; Clarke, Andrew; Deth, Richard

2016-11-01

Food-derived peptides, such as β-casomorphin BCM7, have potential to cross the gastrointestinal tract and blood-brain barrier and are associated with neurological disorders and neurodevelopmental disorders. We previously established a novel mechanism through which BCM7 affects the antioxidant levels in neuronal cells leading to inflammatory consequences. In the current study, we elucidated the effects of casein-derived peptides on neuronal development by using the neurogenesis of neural stem cells (NSCs) as an experimental model. First, the transient changes in intracellular thiol metabolites during NSC differentiation (neurogenesis) were investigated. Next, the neurogenic effects of food-derived opioid peptides were measured, along with changes in intracellular thiol metabolites, redox status and global DNA methylation levels. We observed that the neurogenesis of NSCs was promoted by human BCM7 to a greater extent, followed by A2-derived BCM9 in contrast to bovine BCM7, which induced increased astrocyte formation. The effect was most apparent when human BCM7 was administered for 1day starting on 3days postplating, consistent with immunocytochemistry. Furthermore, neurogenic changes regulated by bovine BCM7 and morphine were associated with an increase in the glutathione/glutathione disulfide ratio and a decrease in the S-adenosylmethionine/S-adenosylhomocysteine ratio, indicative of changes in the redox and the methylation states. Finally, bovine BCM7 and morphine decreased DNA methylation in differentiating NSCs. In conclusion, these results suggest that food-derived opioid peptides and morphine regulated neurogenesis and differentiation of NSCs through changes in the redox state and epigenetic regulation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Diverse effects of lead nitrate on the proliferation, differentiation, and gene expression of stem cells isolated from a dental origin.

PubMed

Abdullah, Mariam; Rahman, Fazliny Abd; Gnanasegaran, Nareshwaran; Govindasamy, Vijayendran; Abu Kasim, Noor Hayaty; Musa, Sabri

2014-01-01

Lead (Pb(2+)) exposure continues to be a significant public health problem. Therefore, it is vital to have a continuous epidemiological dataset for a better understanding of Pb(2+) toxicity. In the present study, we have exposed stem cells isolated from deciduous and permanent teeth, periodontal ligament, and bone marrow to five different types of Pb(2+) concentrations (160, 80, 40, 20, and 10 µM) for 24 hours to identify the adverse effects of Pb(2+) on the proliferation, differentiation, and gene expression on these cell lines. We found that Pb(2+) treatment altered the morphology and adhesion of the cells in a dose-dependent manner. There were no significant changes in terms of cell surface phenotypes. Cells exposed to Pb(2+) continued to differentiate into chondrogenesis and adipogenesis, and a severe downregulation was observed in osteogenesis. Gene expression studies revealed a constant expression of key markers associated with stemness (Oct 4, Rex 1) and DNA repair enzyme markers, but downregulation occurred with some ectoderm and endoderm markers, demonstrating an irregular and untimely differentiation trail. Our study revealed for the first time that Pb(2+) exposure not only affects the phenotypic characteristics but also induces significant alteration in the differentiation and gene expression in the cells.

Tumor necrosis factor-alpha antagonists: differential clinical effects by different biotechnological molecules.

PubMed

Licastro, F; Chiappelli, M; Ianni, M; Porcellini, E

2009-01-01

Inhibitors of tumor necrosis factor-alpha have deeply changed the therapy of several inflammatory human diseases. For instance, clinical management of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis have profoundly benefited after the introduction of new therapeutic tools, such as antagonist of TNF-alpha molecule. These drugs include etanercept, a soluble TNF-alpha receptor antagonist, three anti-TNF-alpha antibodies, adalimumab, infliximab, golimumab and certolizumab a humanized Fab fragment combined with polyethylene glycol. These compounds efficiently inhibit several TNF-alpha biological-mediated effects, however, they have also shown differential clinical efficacy in several trials from different autoimmune diseases. It is of clinical relevance that non-responders to one of these drugs often positively responded to another. Different mechanisms of action and diversity in pharmacokinetics of these three compounds may partially explain different clinical effects. However, partially diverse pathogenetic mechanisms in different diseases also contribute to differential therapeutic responses. Therefore, these apparently homogeneous agents can not be considered equivalent in their clinically efficacy. Differential therapeutic actions of these drugs may be advantageously used in clinical practice and further improve the great potential of individual TNF-alpha inhibitors.

[Effect of chorionic gonadotropin on thymocyte differentiation in the presence of thymus epithelial cells].

PubMed

Kuklina, E M; Shirshev, S V; Sharova, N I; Iarilin, A A

2003-01-01

We studied the effects of the main placental hormone, chorionic gonadotropin, on differentiation of human thymocytes in vitro in the presence of thymic epithelial cells. It was shown that the hormone at a high dose (100 IU/ml) enhanced the epithelium-induced phenotypic maturation of thymocytes, which is registered by an increased expression of the membrane marker CD3 and transition of CD4+8+ thymocytes in the cells with CD4+8- and CD4-8+ phenotypes. In addition, gonadotropin enhanced the proliferative response of thymocytes to the mitogen during their cultivation with the epithelium. The stimulating effect of the hormone on the epithelium-induced differentiation of thymocytes is mediated by the humoral factors of epithelial cells. In addition, gonadotropin at this dose exerts its own differentiating activity with respect to thymocytes and stimulates their phenotypic and functional maturation in a monoculture.

Differentiation of Rat bone marrow Mesenchymal stem cells into Adipocytes and Cardiomyocytes after treatment with platelet lysate

PubMed Central

Homayouni Moghadam, Farshad; Tayebi, Tahereh; Barzegar, Kazem

2016-01-01

Background: Mesenchymal stem cells (MSCs) are multipotential cells and their therapeutic potency is under intense investigation. Studying the effect of different induction factors on MSCs could increase our knowledge about the differentiation potency of these cells. One of the most important sources of these factors in mammalian body is platelet. Platelet lysate (PL) contains many growth factors and therefore, it can be used as a differentiation inducer. In the present study, the effect of PL on differentiation of rat bone marrow MSCs into cardiomyocytes was studied. Materials and Methods: To study the differentiation-inducing effect of PL, MSCs were treated with 2.5, 5 and 10% PL. Early results of this study showed that PL in high concentrations (10%) induces adipogenic differentiation of MSCs. Therefore, to evaluate differentiation to cardiomyocytes, MSCs were cultured in media containing lower levels of PL (2.5% and 5%) and then cardiomyogenic differentiation was induced by treatment with 5-azacytidine. Differentiation of MSCs was evaluated using direct observation of beating cells, immunostaining and real-time PCR techniques. Results: The results of qPCR showed that treatment with PL alone increased the expression of cardiac alpha actinin (CAA) being predictable by earlier observation of beating cells in PL-treated groups. The results of staining assays against cardiac alpha actinin also showed that there were stained cells in PL-treated groups. Conclusion: The results of the present study showed that PL is a powerful induction factor for differentiation of MSCs into different cell lines such as cardiomyocytes and adipocytes. PMID:27047647

Exogenous hydrogen sulfide promotes cell proliferation and differentiation by modulating autophagy in human keratinocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xie, Xin; Dai, Hui; Zhuang, Binyu

The effects and the underlying mechanisms of hydrogen sulfide (H{sub 2}S) on keratinocyte proliferation and differentiation are still less known. In the current study, we investigated the effects and the underlying mechanisms of exogenous H{sub 2}S on keratinocyte proliferation and differentiation. Human keratinocytes (HaCaT cells) were treated with various concentrations (0.05, 0.25, 0.5 and 1 mM) of sodium hydrosulfide (NaHS, a donor of H{sub 2}S) for 24 h. A CCK-8 assay was used to assess cell viability. Western blot analysis was performed to determine the expression levels of proteins associated with differentiation and autophagy. Transmission electron microscopy was performed to observe autophagicmore » vacuoles, and flow cytometry was applied to evaluate apoptosis. NaHS promoted the viability, induced the differentiation, and enhanced autophagic activity in a dose-dependent manner in HaCaT cells but had no effect on cell apoptosis. Blockage of autophagy by ATG5 siRNA inhibited NaHS-induced cell proliferation and differentiation. The current study demonstrated that autophagy in response to exogenous H{sub 2}S treatment promoted keratinocyte proliferation and differentiation. Our results provide additional insights into the potential role of autophagy in keratinocyte proliferation and differentiation. - Highlights: • Exogenous H{sub 2}S promotes keratinocyte proliferation and differentiation. • The effects of H{sub 2}S on proliferation and differentiation is modulated by autophagy. • Exogenous H{sub 2}S has no effect on keratinocyte apoptosis.« less

Detection of a Sharp Structural Boundary in Lowermost Mantle Beneath Alaska by Core Phase PKPbc-df Differential Travel Times - Observation from the Anomalous South Sandwich Islands to Alaska Path

NASA Astrophysics Data System (ADS)

Xin, L.; Kawakatsu, H.; Takeuchi, N.

2017-12-01

Differential travel time residuals of PKPbc and PKPdf for the path from South Sandwich Islands (SSI) to Alaska are usually used to constrain anisotropy of the western hemisphere of the Earth's inner-core. For this polar path, it has been found that PKPbc-df differential residuals are generally anomalously larger than data that sample other regions, and also show strong lateral variation. Due to sparse distribution of seismic stations in Alaska in early times, previous researches have been unable to propose a good model to explain this particular data set. Using data recorded by the current dense stations in Alaska for SSI earthquakes, we reexamine the anomalous behavior of core phase PKPbc-df differential travel times and try to explain the origin. The data sample the inner-core for the polar paths, as well as the lowermost mantle beneath Alaska. Our major observations are: (1) fractional travel time residuals of PKPbc-df increase rapidly within 2° (up to 1%). (2) A clear shift of the residual pattern could be seen for earthquakes with different locations. (3) The residual shows systematic lateral variation: at northern part, no steep increase of residual can be seen. A sharp lateral structural boundary with a P-wave velocity contrast of about 3% at lowermost mantle beneath East Alaska is invoked to explain the steep increase of the observed residuals. By combining the effects of a uniformly anisotropic inner-core and the heterogeneity, the observed residual patterns could be well reproduced. This high velocity anomaly might be related with an ancient subducted slab. Lateral variation of the PKPbc-df residuals suggests that the heterogeneity layer is not laterally continuous and may terminate beneath Northeastern Alaska. We also conclude that core phases may be strongly affected by heterogeneities at lowermost mantle, and should be carefully treated if they are used to infer the inner-core structure.

The effects and mechanisms of clinorotation on proliferation and differentiation in bone marrow mesenchymal stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yan, Ming; Wang, Yongchun; Yang, Min

Data from human and rodent studies have demonstrated that microgravity induces observed bone loss in real spaceflight or simulated experiments. The decrease of bone formation and block of maturation may play important roles in bone loss induced by microgravity. The aim of this study was to investigate the changes of proliferation and differentiation in bone marrow mesenchymal stem cells (BMSCs) induced by simulated microgravity and the mechanisms underlying it. We report here that clinorotation, a simulated model of microgravity, decreased proliferation and differentiation in BMSCs after exposure to 48 h simulated microgravity. The inhibited proliferation are related with blocking the cellmore » cycle in G2/M and enhancing the apoptosis. While alterations of the osteoblast differentiation due to the decreased SATB2 expression induced by simulated microgravity in BMSCs. - Highlights: • Simulated microgravity inhibited proliferation and differentiation in BMSCs. • The decreased proliferation due to blocked cell cycle and enhanced the apoptosis. • The inhibited differentiation accounts for alteration of SATB2, Hoxa2 and Cbfa1.« less

Distinct Effects of RGD-glycoproteins on Integrin-Mediated Adhesion and Osteogenic Differentiation of Human Mesenchymal Stem Cells

PubMed Central

Schwab, Elisabeth H.; Halbig, Maria; Glenske, Kristina; Wagner, Alena-Svenja; Wenisch, Sabine; Cavalcanti-Adam, Elisabetta A.

2013-01-01

The detailed interactions of mesenchymal stem cells (MSCs) with their extracellular matrix (ECM) and the resulting effects on MSC differentiation are still largely unknown. Integrins are the main mediators of cell-ECM interaction. In this study, we investigated the adhesion of human MSCs to fibronectin, vitronectin and osteopontin, three ECM glycoproteins which contain an integrin-binding sequence, the RGD motif. We then assayed MSCs for their osteogenic commitment in the presence of the different ECM proteins. As early as 2 hours after seeding, human MSCs displayed increased adhesion when plated on fibronectin, whereas no significant difference was observed when adhering either to vitronectin or osteopontin. Over a 10-day observation period, cell proliferation was increased when cells were cultured on fibronectin and osteopontin, albeit after 5 days in culture. The adhesive role of fibronectin was further confirmed by measurements of cell area, which was significantly increased on this type of substrate. However, integrin-mediated clusters, namely focal adhesions, were larger and more mature in MSCs adhering to vitronectin and osteopontin. Adhesion to fibronectin induced elevated expression of α5-integrin, which was further upregulated under osteogenic conditions also for vitronectin and osteopontin. In contrast, during osteogenic differentiation the expression level of β3-integrin was decreased in MSCs adhering to the different ECM proteins. When MSCs were cultured under osteogenic conditions, their commitment to the osteoblast lineage and their ability to form a mineralized matrix in vitro was increased in presence of fibronectin and osteopontin. Taken together these results indicate a distinct role of ECM proteins in regulating cell adhesion, lineage commitment and phenotype of MSCs, which is due to the modulation of the expression of specific integrin subunits during growth or osteogenic differentiation. PMID:24324361

Distinct effects of RGD-glycoproteins on Integrin-mediated adhesion and osteogenic differentiation of human mesenchymal stem cells.

PubMed

Schwab, Elisabeth H; Halbig, Maria; Glenske, Kristina; Wagner, Alena-Svenja; Wenisch, Sabine; Cavalcanti-Adam, Elisabetta A

2013-01-01

The detailed interactions of mesenchymal stem cells (MSCs) with their extracellular matrix (ECM) and the resulting effects on MSC differentiation are still largely unknown. Integrins are the main mediators of cell-ECM interaction. In this study, we investigated the adhesion of human MSCs to fibronectin, vitronectin and osteopontin, three ECM glycoproteins which contain an integrin-binding sequence, the RGD motif. We then assayed MSCs for their osteogenic commitment in the presence of the different ECM proteins. As early as 2 hours after seeding, human MSCs displayed increased adhesion when plated on fibronectin, whereas no significant difference was observed when adhering either to vitronectin or osteopontin. Over a 10-day observation period, cell proliferation was increased when cells were cultured on fibronectin and osteopontin, albeit after 5 days in culture. The adhesive role of fibronectin was further confirmed by measurements of cell area, which was significantly increased on this type of substrate. However, integrin-mediated clusters, namely focal adhesions, were larger and more mature in MSCs adhering to vitronectin and osteopontin. Adhesion to fibronectin induced elevated expression of α₅-integrin, which was further upregulated under osteogenic conditions also for vitronectin and osteopontin. In contrast, during osteogenic differentiation the expression level of β₃-integrin was decreased in MSCs adhering to the different ECM proteins. When MSCs were cultured under osteogenic conditions, their commitment to the osteoblast lineage and their ability to form a mineralized matrix in vitro was increased in presence of fibronectin and osteopontin. Taken together these results indicate a distinct role of ECM proteins in regulating cell adhesion, lineage commitment and phenotype of MSCs, which is due to the modulation of the expression of specific integrin subunits during growth or osteogenic differentiation.

Second-harmonic generation microscopy used to evaluate the effect of the dimethyl sulfoxide in the cryopreservation process in collagen fibers of differentiated chondrocytes

NASA Astrophysics Data System (ADS)

Andreoli-Risso, M. F.; Duarte, A. S. S.; Ribeiro, T. B.; Bordeaux-Rego, P.; Luzo, A.; Baratti, M. O.; Adur, J.; de Thomaz, A. A.; Pelegati, V. B.; Carvalho, H. F.; Cesar, C. L.; Kharmadayan, P.; Costa, F. F.; Olalla-Saad, S. T.

2012-03-01

Cartilaginous lesions are a significant public health problem and the use of adult stem cells represents a promising therapy for this condition. Cryopreservation confers many advantages for practitioners engaged in cell-based therapies. However, conventional slow freezing has always been associated with damage and mortality due to intracellular ice formation, cryoprotectant toxicity, and dehydration. The aim of this work is to observe the effect of the usual Dimethyl Sulfoxide (DMSO) cryopreservation process on the architecture of the collagen fiber network of chondrogenic cells from mesenchymal stem cells by Second Harmonic Generation (SHG) microscopy. To perform this study we used Mesenchymal Stem Cells (MSC) derived from adipose tissue which presents the capacity to differentiate into other lineages such as osteogenic, adipogenic and chondrogenic lineages. Mesenchymal stem cells obtained after liposuction were isolated digested by collagenase type I and characterization was carried out by differentiation of mesodermic lineages, and flow cytometry using specific markers. The isolated MSCs were cryopreserved by the DMSO technique and the chondrogenic differentiation was carried out using the micromass technique. We then compared the cryopreserved vs non-cryopreserved collagen fibers which are naturally formed during the differentiation process. We observed that noncryopreserved MSCs presented a directional trend in the collagen fibers formed which was absent in the cryopreserved MSCs. We confirmed this trend quantitatively by the aspect ratio obtained by Fast Fourier Transform which was 0.76 for cryopreserved and 0.52 for non-cryopreserved MSCs, a statistical significant difference.

Effects of Adenosine Triphosphate on Proliferation and Odontoblastic Differentiation of Human Dental Pulp Cells.

PubMed

Wang, Wei; Yi, Xiaosong; Ren, Yanfang; Xie, Qiufei

2016-10-01

Adenosine 5'-triphosphate (ATP) is a potent signaling molecule that regulates diverse biological activities in cells. Its effects on human dental pulp cells (HDPCs) remain unknown. This study aimed to examine the effects of ATP on proliferation and differentiation of HDPCs. Reverse transcription polymerase chain reaction was performed to explore the mRNA expression of P2 receptor subtypes. Cell Counting Kit-8 test and flow cytometry analysis were used to examine the effects of ATP on proliferation and cell cycle of HDPCs. The effects of ATP on differentiation of HDPCs were examined by using alizarin red S staining, energy-dispersive x-ray analysis, Western blot analysis, and real-time polymerase chain reaction. The purinoceptors P2X3, P2X4, P2X5, P2X7, and all P2Y receptor subtypes were confirmed to present in HDPCs. ATP enhanced HDPC proliferation at 10 μmol/L concentration. However, it inhibited cell proliferation by arresting the cell cycle in G0G1 phase (P < .05 versus control) and induced odontoblastic differentiation, ERK/MAPK activation, and dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP) mRNA transcriptions at 800 μmol/L concentration. Suramin, an ATP receptor antagonist, inhibited ERK/MAPK activation and HDPC odontoblastic differentiation (P < .05 versus control). Extracellular ATP activates P2 receptors and downstream signaling events that induce HDPC odontogenic differentiation. Thus, ATP may promote dental pulp tissue healing and repair through P2 signaling. Results provide new insights into the molecular regulation of pulpal wound healing. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Using Technology to Facilitate Differentiated High School Science Instruction

NASA Astrophysics Data System (ADS)

Maeng, Jennifer L.

2017-10-01

This qualitative investigation explored the beliefs and practices of one secondary science teacher, Diane, who differentiated instruction and studied how technology facilitated her differentiation. Diane was selected based on the results of a previous study, in which data indicated that Diane understood how to design and implement proactively planned, flexible, engaging instructional activities in response to students' learning needs better than the other study participants. Data for the present study included 3 h of semi-structured interview responses, 37.5 h of observations of science instruction, and other artifacts such as instructional materials. This variety of data allowed for triangulation of the evidence. Data were analyzed using a constant comparative approach. Results indicated that technology played an integral role in Diane's planning and implementation of differentiated science lessons. The technology-enhanced differentiated lessons employed by Diane typically attended to students' different learning profiles or interest through modification of process or product. This study provides practical strategies for science teachers beginning to differentiate instruction, and recommendations for science teacher educators and school and district administrators. Future research should explore student outcomes, supports for effective formative assessment, and technology-enhanced readiness differentiation among secondary science teachers.

Differential effects of prenatal testosterone on lateralization of handedness and language.

PubMed

Lust, Jessica M; Geuze, Reint H; Van de Beek, Cornelieke; Cohen-Kettenis, Peggy T; Bouma, Anke; Groothuis, Ton G G

2011-09-01

Handedness is the most noticeable functional expression of cerebral lateralization in humans. However, its developmental process and plasticity remain elusive. It has been postulated that prenatal testosterone (pT) has an effect on human lateralization development. In the present study we examined the relationship between pT and handedness and compared the outcome to previously published data on language lateralization in the same children. pT was assessed from amniotic fluid of healthy pregnant women using radioimmunoassay. Strength and direction of handedness of the children (n = 65 [31 girls, 34 boys], mean age [years]: 6.43, range: 5.97-7.53) was assessed based on hand choice during performance of age appropriate tasks. Regression procedures and the Olkin & Siotani Z-statistic were used. Results demonstrate that higher pT exposure was related to a decrease in strength of handedness (R² = .11, p = .01). The analysis shows that pT has quite stronger explanatory power than sex by itself, although there may be an additional effect of sex independent from pT. In a subgroup of these children we recently reported that higher levels of pT are related to increased left hemisphere dominance for language. Analyses show that pT is differentially related to handedness and language lateralization in these children (Z > 2.75, p < .003). Results imply a differential effect of pT on language lateralization and handedness. This may be explained by differential sensitivity of different areas of the corpus callosum or hemispheres for androgens, fuelling the ongoing debate about the relationship between prenatal exposure to testosterone and lateralization of brain and behavior. PsycINFO Database Record (c) 2011 APA, all rights reserved.

Differential effect of buffering agents on the crystallization of gemcitabine hydrochloride in frozen solutions.

PubMed

Patel, Mehulkumar; Munjal, Bhushan; Bansal, Arvind K

2014-08-25

The purpose of this study was to evaluate the differential effect of buffering agents on the crystallization of gemcitabine hydrochloride (GHCl) in frozen solutions. Four buffering agents, viz. citric acid (CA), malic acid (MA), succinic acid (SA) and tartaric acid (TA) were selected and their effect on GHCl crystallization was monitored using standard DSC and low temperature XRD. Onset of GHCl crystallization during heating run in DSC was measured to compare the differential effect of buffering agents. Glass transition temperature (Tg'), unfrozen water content in the freeze concentrate and crystallization propensity of the buffering agents was also determined for mechanistic understanding of the underlying effects. CA and MA inhibited while SA facilitated crystallization of GHCl even at 25 mM concentration. Increasing the concentration enhanced their effect. However, TA inhibited GHCl crystallization at concentrations <100mM and facilitated it at concentrations ≥100 mM. Lyophilization of GHCl with either SA or TA yielded elegant cakes, while CA and MA caused collapse. Tg' failed to explain the inhibitory effects of CA, MA and TA as all buffering agents lowered the Tg' of the system. Differential effect of buffering agents on GHCl crystallization could be explained by consideration of two opposing factors: (i) their own crystallization tendency and (ii) unfrozen water content in the freeze concentrate. In conclusion, it was established that API crystallization in frozen solution is affected by the type and concentration of the buffering agents. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of coumarins on HL-60 cell differentiation.

PubMed

Kawaii, S; Tomono, Y; Katase, E; Ogawa, K; Yano, M

2000-01-01

Twenty-eight coumarins, including 7 furocoumarins, were examined for their activity of induction of terminal differentiation of human promyelocytic leukemia cells (HL-60) by nitro blue tetrazolium (NBT) reducing, nonspecific esterase, specific esterase and phagocytic activities. Esculetin, nordalbergin, 6,7-dihydroxy-4-methylcoumarin and imperatorin had strong activity among the coumarins examined. HL-60 cells treated with these coumarins differentiated into mature monocyte/macrophage. The structure-activity relationship established from the results revealed that 6,7-dihydroxy moiety had an important role in the induction of differentiation of HL-60.

Differential results integrated with continuous and discrete gravity measurements between nearby stations

NASA Astrophysics Data System (ADS)

Xu, Weimin; Chen, Shi; Lu, Hongyan

2016-04-01

Integrated gravity is an efficient way in studying spatial and temporal characteristics of the dynamics and tectonics. Differential measurements based on the continuous and discrete gravity observations shows highly competitive in terms of both efficiency and precision with single result. The differential continuous gravity variation between the nearby stations, which is based on the observation of Scintrex g-Phone relative gravimeters in every single station. It is combined with the repeated mobile relative measurements or absolute results to study the regional integrated gravity changes. Firstly we preprocess the continuous records by Tsoft software, and calculate the theoretical earth tides and ocean tides by "MT80TW" program through high precision tidal parameters from "WPARICET". The atmospheric loading effects and complex drift are strictly considered in the procedure. Through above steps we get the continuous gravity in every station and we can calculate the continuous gravity variation between nearby stations, which is called the differential continuous gravity changes. Then the differential results between related stations is calculated based on the repeated gravity measurements, which are carried out once or twice every year surrounding the gravity stations. Hence we get the discrete gravity results between the nearby stations. Finally, the continuous and discrete gravity results are combined in the same related stations, including the absolute gravity results if necessary, to get the regional integrated gravity changes. This differential gravity results is more accurate and effective in dynamical monitoring, regional hydrologic effects studying, tectonic activity and other geodynamical researches. The time-frequency characteristics of continuous gravity results are discussed to insure the accuracy and efficiency in the procedure.

Negative differential resistance in GaN nanocrystals above room temperature.

PubMed

Chitara, Basant; Ivan Jebakumar, D S; Rao, C N R; Krupanidhi, S B

2009-10-07

Negative differential resistance (NDR) has been observed for the first time above room temperature in gallium nitride nanocrystals synthesized by a simple chemical route. Current-voltage characteristics have been used to investigate this effect through a metal-semiconductor-metal (M-S-M) configuration on SiO2. The NDR effect is reversible and reproducible through many cycles. The threshold voltage is approximately 7 V above room temperature.

Differential effect of EGFR inhibitors on tamoxifen-resistant breast cancer cells.

PubMed

Kim, Sangmin; Lee, Jeongmin; Oh, Soo Jin; Nam, Seok Jin; Lee, Jeong Eon

2015-09-01

Although tamoxifen is the most common and effective therapy for treatment of estrogen receptor-α (ER-α) breast cancer patients, resistance of endocrine therapy occurs, either de novo or acquired during therapy. Here, we investigated the clinical value of epidermal growth factor receptor (EGFR) in tamoxifen-resistant (TamR) patients and the differential effect of EGFR inhibitors, neratinib and gefitinib, on TamR breast cancer cell model. The morphology of TamR MCF7 cells showed mesenchymal phenotypes and did not induce cell death by tamoxifen treatment compared with tamoxifen‑sensitive (TamS) MCF7 cells. In addition, mesenchymal marker proteins, including N-cadherin (N-cad), fibronectin (FN), and Slug, significantly increased in TamR cells. In contrast, ER-α and E-cadherin (E-cad) were greatly decreased. We also found that the levels of EGFR and HER2 expression were increased in TamR cells. Furthermore, we observed that EGFR expression was directly involved with poor prognosis of tamoxifen-treated breast cancer patients using the GSE1378 date set. Thus, we treated TamR and TamS cells with EGFR inhibitors, neratinib and gefitinib, respectively. Interestingly, neratinib induced apoptotic cell death of TamR but not gefitinib. Cleaved PARP-1 expression was also increased by neratinib treatment in TamR cells. Therefore, we suggest that neratinib may be a potential therapeutic drug for treating TamR breast cancer.

Effects of a History of Differential Reinforcement on Preference for Choice

ERIC Educational Resources Information Center

Karsina, Allen; Thompson, Rachel H.; Rodriguez, Nicole M.

2011-01-01

The effects of a history of differential reinforcement for selecting a free-choice versus a restricted-choice stimulus arrangement on the subsequent responding of 7 undergraduates in a computer-based game of chance were examined using a concurrent-chains arrangement and a multiple-baseline-across-participants design. In the free-choice…

Steroids, aromatase and sex differentiation of the newt Pleurodeles waltl.

PubMed

Kuntz, S; Chardard, D; Chesnel, A; Grillier-Vuissoz, I; Flament, S

2003-01-01

In the newt Pleurodeles waltl, genetic sex determination obeys female heterogamety (female ZW, male ZZ). In this species as in most of non-mammalian vertebrates, steroid hormones play a key role in sexual differentiation of gonads. In that context, male to female sex reversal can be obtained by treatment of ZZ larvae with estradiol. Male to female sex reversal has also been observed following treatment of ZZ larvae with testosterone, a phenomenon that was called the "paradoxical effect". Female to male sex reversal occurs when ZW larvae are reared at 32 degrees C during a thermosensitive period (TSP) that takes place from stage 42 to stage 54 of development. Since steroids play an important part in sex differentiation, we focussed our studies on the estrogen-producing enzyme aromatase during normal sex differentiation as well as in experimentally induced sex reversal situations. Our results based on treatment with non-aromatizable androgens, aromatase activity measurements and aromatase expression studies demonstrate that aromatase (i) is differentially active in ZZ and ZW larvae, (ii) is involved in the paradoxical effect and (iii) might be a target of temperature. Thus, the gene encoding aromatase might be one of the master genes in the process leading to the differentiation of the gonad in Pleurodeles waltl. Copyright 2003 S. Karger AG, Basel

The Effect of Differentiation Approach Developed on Creativity of Gifted Students: Cognitive and Affective Factors

ERIC Educational Resources Information Center

Altintas, Esra; Özdemir, Ahmet S.

2015-01-01

The aim of the study is to develop a differentiation approach for the mathematics education of gifted middle school students and to determine the effect of the differentiation approach on creative thinking skills of gifted students based on both cognitive and affective factors. In this context, the answer to the following question was searched:…

Differential effects of malignant mesothelioma cells on THP-1 monocytes and macrophages.

PubMed

Izzi, Valerio; Chiurchiù, Valerio; D'Aquilio, Fabiola; Palumbo, Camilla; Tresoldi, Ilaria; Modesti, Andrea; Baldini, Patrizia M

2009-02-01

Malignant mesothelioma (MM) is a highly fatal tumor arising from inner body membranes, whose extensive growth is facilitated by its week immunogenicity and by its ability to blunt the immune response which should arise from the huge mass of leukocytes typically infiltrating this tumor. It has been reported that the inflammatory infiltrate found in MM tissues is characterized by a high prevalence of macrophages. Thus, in this work we evaluated the ability of human MM cells to modulate the inflammatory phenotype of human THP-1 monocytes and macrophages, a widely used in vitro model of monocyte/macrophage differentiation. Furthermore, we tested the hypothesis that the exposure to MM cells could alter the differentiation of THP-1 monocytes favoring the development of alternatively activated, tumor-supporting macrophages. Our data prove for the first time that MM cells can polarize monocytes towards an altered inflammatory phenotype and macrophages towards an immunosuppressive phenotype. Moreover, we demonstrate that monocytes cocultivated with MM cells 'keep a memory' of their encounter with the tumor which influences their differentiation to macrophages. On the whole, we provide evidence that MM cells exert distinct, cell-specific effects on monocytes and macrophages. The thorough characterization of such effects may be of a crucial importance for the rational design of new immunotherapeutic protocols.

Limitations to Dual Frequency Ionosphere Corrections for Frequency Switched K-Q-Band Observations with the VLBA

NASA Technical Reports Server (NTRS)

Lanyi, Gabor; Gordon, David; Sovers, Ojars J.

2004-01-01

A series of VLBA experiments were carried out at K and Q bands for astrometry and imaging within the KQ VLBI Survey Collaboration. The paired K and Q observations of each source are separated by approximately 3 minutes of time. We investigate the delay effect of the ionosphere between K and Q bands involving the interscan separation. This differential delay effect is intermixed with the differential fluctuation effect of the troposphere.

The Effect of Recombinant Tyrosine Hydroxylase Expression on the Neurogenic Differentiation Potency of Mesenchymal Stem Cells

PubMed Central

Duruksu, Gokhan; Karaoz, Erdal

2018-01-01

Objective Tyrosine hydroxylase (TH) is a rate-limiting enzyme in dopamine synthesis, making the enhancement of its activity a target for ensuring sufficient dopamine levels. Rat bone marrow mesenchymal stem cells (rBM-MSCs) are known to synthesize TH after differentiating into neuronal cells through chemical induction, but the effect of its ectopic expression on these cells has not yet been determined. This study investigated the effects of ectopic recombinant TH expression on the stemness characteristics of rBM-MSCs. Methods After cloning, a cell line with stable TH expression was maintained, and the proliferation, the gene expression profile, and differentiation potential of rBM-MSCs were analyzed. Analysis of the cells showed an increment in the proliferation rate that could be reversed by the neutralization of TH. Results The constitutive expression of TH in rBM-MSCs was successfully implemented, without significantly affecting their osteogenic and adipogenic differentiation potential. TH expression improved the expression of other neuronal markers, such as glial fibrillary acidic protein, β-tubulin, nestin, and c-Fos, confirming the neurogenic differentiation capacity of the stem cells. The expression of brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) significantly increased after the chemical induction of neurogenic differentiation. Conclusion In this study, the expression of recombinant TH improved the neuroprotective effect of MSCs by upregulating the expression of BDNF and CNTF. Although the neuronal markers were upregulated, the expression of recombinant TH alone in rBM-MSCs was not sufficient for MSCs to differentiate into neurogenic cell lines. PMID:29656620

Differential effects of gender on entropy perception

NASA Astrophysics Data System (ADS)

Satcharoen, Kleddao

2017-12-01

The purpose of this research is to examine differences in perception of entropy (color intensity) between male and female computer users. The objectives include identifying gender-based differences in entropy intention and exploring the potential effects of these differences (if any) on user interface design. The research is an effort to contribute to an emerging field of interest in gender as it relates to science, engineering and technology (SET), particularly user interface design. Currently, there is limited evidence on the role of gender in user interface design and in use of technology generally, with most efforts at gender-differentiated or customized design based on stereotypes and assumptions about female use of technology or the assumption of a default position based on male preferences. Image entropy was selected as a potential characteristic where gender could be a factor in perception because of known differences in color perception acuity between male and female individuals, even where there is no known color perception abnormality (which is more common with males). Although the literature review suggested that training could offset differences in color perception and identification, tests in untrained subject groups routinely show that females are more able to identify, match, and differentiate colors, and that there is a stronger emotional and psychosocial association of color for females. Since image entropy is associated with information content and image salience, the ability to identify areas of high entropy could make a difference in user perception and technological capabilities.

Differential Effects of Estrogen and Progesterone on Genetic and Environmental Risk for Emotional Eating in Women

PubMed Central

Klump, Kelly L.; O’Connor, Shannon M.; Hildebrandt, Britny A.; Keel, Pamela K.; Neale, Michael; Sisk, Cheryl L.; Boker, Steven; Burt, S. Alexandra

2016-01-01

Recent data show shifts in genetic and environmental influences on emotional eating across the menstrual cycle, with significant shared environmental influences during pre-ovulation, and primarily genetic effects during post-ovulation. Factors driving differential effects are unknown, although increased estradiol during pre-ovulation and increased progesterone during post-ovulation are thought to play a role. We indirectly investigated this possibility by examining whether overall levels of estradiol and progesterone differentially impact genetic and environmental risk for emotional eating in adult female twins (N = 571) drawn from the MSU Twin Registry. Emotional eating, estradiol levels, and progesterone levels were assessed daily and then averaged to create aggregate measures for analysis. As predicted, shared environmental influences were significantly greater in twins with high estradiol levels, whereas additive genetic effects increased substantially across low versus high progesterone groups. Results highlight significant and differential effects of ovarian hormones on etiologic risk for emotional eating in adulthood. PMID:27747142

Kaempferol impedes IL-32-induced monocyte-macrophage differentiation.

PubMed

Nam, Sun-Young; Jeong, Hyun-Ja; Kim, Hyung-Min

2017-08-25

Kaempferol possesses a wide range of therapeutic properties, including antioxidant, anti-inflammatory, and anticancer properties. The present study sought to evaluate the effects and possible pharmacological mechanisms of kaempferol on interleukin (IL)-32-induced monocyte-macrophage differentiation. In this study, we performed flow cytometry assay, immunocytochemical staining, quantitative real-time PCR, enzyme-linked immuno sorbent assay, caspase-1 assay, and Western blotting to observe the effects and underlying mechanisms of kaempferol using the human monocyte cell line THP-1. The flow cytometry, immunocytochemical staining, and real-time PCR results show that kaempferol attenuated IL-32-induced monocyte differentiation to product macrophage-like cells. Kaempferol decreased the production and mRNA expression of pro-inflammatory cytokines, in this case thymic stromal lymphopoietin (TSLP), IL-1β, tumor necrosis factor (TNF)-α, and IL-8. Furthermore, kaempferol inhibited the IL-32-induced activation of p38 and nuclear factor-κB in a dose-dependent manner in THP-1 cells. Kaempferol also ameliorated the lipopolysaccharide-induced production of the inflammatory mediators TSLP, IL-1β, TNF-α, IL-8, and nitric oxide of macrophage-like cells differentiated by IL-32. In brief, our findings may provide new mechanistic insights into the anti-inflammatory effects of kaempferol. Copyright © 2017 Elsevier B.V. All rights reserved.

Differential toxic effects of azathioprine, 6-mercaptopurine and 6-thioguanine on human hepatocytes.

PubMed

Petit, Elise; Langouet, Sophie; Akhdar, Hanane; Nicolas-Nicolaz, Christophe; Guillouzo, André; Morel, Fabrice

2008-04-01

Thiopurines (azathioprine, 6-mercaptopurine and 6-thioguanine) are therapeutic compounds widely administered in the clinic for their multiple uses (autoimmune diseases, post-transplant immunosuppression and cancer). Despite these advantages, their therapeutic potential is limited by occasional adverse effects (myelotoxicity and hepatotoxicity) and by a relatively frequent lack of efficacy. Previous studies have demonstrated that azathioprine decreased the viability of rat hepatocytes. In order to investigate cytotoxic effects of thiopurines in human liver, we used primary human hepatocytes and a highly differentiated human hepatoma cell line, HepaRG, treated or not with azathioprine, 6-mercaptopurine and 6-thioguanine. In parallel, expression of the genes involved in the metabolism of thiopurines, glutathione synthesis and antioxidant defences was measured by quantitative PCR. We clearly demonstrate that human liver parenchymal cells were much less sensitive than rat hepatocytes to thiopurine treatments. The toxic effects appeared after 96 h of treatment while ATP depletion was observed after a 24 h incubation with azathioprine and 6-mercaptopurine. Toxic effects were more pronounced for azathioprine and 6-mercaptopurine, when compared to 6-thioguanine, and might explain glutathione synthesis and antioxidant enzyme induction only by these two drugs. Finally, we also demonstrate for the first time an up-regulation by azathioprine and 6-mercaptopurine of inosine monophosphate dehydrogenase which might have consequences on the de novo biosynthesis of guanine nucleotides and thiopurines metabolism.

Differential neurobiological effects of expert advice on risky choice in adolescents and adults.

PubMed

Engelmann, Jan B; Moore, Sara; Monica Capra, C; Berns, Gregory S

2012-06-01

We investigated behavioral and neurobiological mechanisms by which risk-averse advice, provided by an expert, affected risky decisions across three developmental groups [early adolescents (12-14 years), late adolescents (15-17 years), adults (18+ years)]. Using cumulative prospect theory, we modeled choice behavior during a risky-choice task. Results indicate that advice had a significantly greater impact on risky choice in both adolescent groups than in adults. Using functional magnetic resonance imaging, we investigated the neural correlates of this behavioral effect. Developmental effects on correlations between brain activity and valuation parameters were obtained in regions that can be classified into (i) cognitive control regions, such as dorsolateral prefrontal cortex (DLPFC) and ventrolateral PFC; (ii) social cognition regions, such as posterior temporoparietal junction; and (iii) reward-related regions, such as ventromedial PFC (vmPFC) and ventral striatum. Within these regions, differential effects of advice on neural correlates of valuation were observed across development. Specifically, advice increased the correlation strength between brain activity and parameters reflective of safe choice options in adolescent DLPFC and decreased correlation strength between activity and parameters reflective of risky choice options in adult vmPFC. Taken together, results indicate that, across development, distinct brain systems involved in cognitive control and valuation mediate the risk-reducing effect of advice during decision making under risk via specific enhancements and reductions of the correlation strength between brain activity and valuation parameters.

Effects of Co-Culture Media on Hepatic Differentiation of hiPSC with or without HUVEC Co-Culture

PubMed Central

Freyer, Nora; Greuel, Selina; Knöspel, Fanny; Strahl, Nadja; Amini, Leila; Jacobs, Frank; Monshouwer, Mario; Zeilinger, Katrin

2017-01-01

The derivation of hepatocytes from human induced pluripotent stem cells (hiPSC) is of great interest for applications in pharmacological research. However, full maturation of hiPSC-derived hepatocytes has not yet been achieved in vitro. To improve hepatic differentiation, co-cultivation of hiPSC with human umbilical vein endothelial cells (HUVEC) during hepatic differentiation was investigated in this study. In the first step, different culture media variations based on hepatocyte culture medium (HCM) were tested in HUVEC mono-cultures to establish a suitable culture medium for co-culture experiments. Based on the results, two media variants were selected to differentiate hiPSC-derived definitive endodermal (DE) cells into mature hepatocytes with or without HUVEC addition. DE cells differentiated in mono-cultures in the presence of those media variants showed a significant increase (p < 0.05) in secretion of α-fetoprotein and in activities of cytochrome P450 (CYP) isoenzymes CYP2B6 and CYP3A4 as compared with cells differentiated in unmodified HCM used as control. Co-cultivation with HUVEC did not further improve the differentiation outcome. Thus, it can be concluded that the effect of the used medium outweighed the effect of HUVEC co-culture, emphasizing the importance of the culture medium composition for hiPSC differentiation. PMID:28783133

Effects of Co-Culture Media on Hepatic Differentiation of hiPSC with or without HUVEC Co-Culture.

PubMed

Freyer, Nora; Greuel, Selina; Knöspel, Fanny; Strahl, Nadja; Amini, Leila; Jacobs, Frank; Monshouwer, Mario; Zeilinger, Katrin

2017-08-07

The derivation of hepatocytes from human induced pluripotent stem cells (hiPSC) is of great interest for applications in pharmacological research. However, full maturation of hiPSC-derived hepatocytes has not yet been achieved in vitro. To improve hepatic differentiation, co-cultivation of hiPSC with human umbilical vein endothelial cells (HUVEC) during hepatic differentiation was investigated in this study. In the first step, different culture media variations based on hepatocyte culture medium (HCM) were tested in HUVEC mono-cultures to establish a suitable culture medium for co-culture experiments. Based on the results, two media variants were selected to differentiate hiPSC-derived definitive endodermal (DE) cells into mature hepatocytes with or without HUVEC addition. DE cells differentiated in mono-cultures in the presence of those media variants showed a significant increase ( p < 0.05) in secretion of α-fetoprotein and in activities of cytochrome P450 (CYP) isoenzymes CYP2B6 and CYP3A4 as compared with cells differentiated in unmodified HCM used as control. Co-cultivation with HUVEC did not further improve the differentiation outcome. Thus, it can be concluded that the effect of the used medium outweighed the effect of HUVEC co-culture, emphasizing the importance of the culture medium composition for hiPSC differentiation.

Improved Carbon Flux Observations over Urban Areas Using Carbonyl Sulfide (COS) to Differentiate Contributions from Biosphere

NASA Astrophysics Data System (ADS)

Whelan, M.; LaFranchi, B. W.; Bambha, R.; Michelsen, H. A.; Fischer, M. L.; Graven, H. D.; Baker, I. T.; Guilderson, T.; Campbell, J. E.

2016-12-01

Direct measurement and attribution of carbon exchange over urban areas is challenging because of the heterogeneity of the landscape and errors introduced by flux source partitioning. One important contribution to uncertainty is the influence of the urban biosphere on the regional carbon budget. Atmospheric observations of carbonyl sulfide (COS) are an emerging tool for estimating gross primary productivity: COS is consumed in plant leaves by parallel pathways to CO2 uptake, without the additional complexity of an analogous respiration term. This study makes use of COS measurements to better understand fluctuations in total CO2 concentrations over an urban region due to the balance of photosynthesis and respiration. In situ ground-based observations of trace gas concentrations were made from a tower in Livermore, CA, USA, and interpreted with WRF-STILT back trajectories and gridded data sets (e.g. VULCAN, a new anthropogenic COS inventory), supplemented with biosphere models (SiB, CASA-GFED3). CO2, 14CO2, and CO observations were used to first parse the contribution of fossil fuel emissions to total CO2. Changes in the remainder CO2 was differentiated as the sum of biosphere components with associated uncertainties. This approach could be used to better validate carbon emissions reduction measures and ecosytem-based carbon capture projects on the regional scale.

Silver nanoparticles impede phorbol myristate acetate-induced monocyte-macrophage differentiation and autophagy

NASA Astrophysics Data System (ADS)

Xu, Yingying; Wang, Liming; Bai, Ru; Zhang, Tianlu; Chen, Chunying

2015-09-01

Monocytes/macrophages are important constituents of the innate immune system. Monocyte-macrophage differentiation is not only crucial for innate immune responses, but is also related to some cardiovascular diseases. Silver nanoparticles (AgNPs) are one of the most widely used nanomaterials because of their broad-spectrum antimicrobial properties. However, the effect of AgNPs on the functions of blood monocytes is scarcely reported. Here, we report the impedance effect of AgNPs on THP-1 monocyte differentiation, and that this effect was mediated by autophagy blockade and lysosomal impairment. Firstly, AgNPs inhibit phorbol 12-myristate 13-acetate (PMA)-induced monocyte differentiation by down-regulating both expression of surface marker CD11b and response to lipopolysaccharide (LPS) stimulation. Secondly, autophagy is activated during PMA-induced THP-1 monocyte differentiation, and the autophagy inhibitor chloroquine (CQ) can inhibit this process. Thirdly, AgNPs block the degradation of the autophagy substrate p62 and induce autophagosome accumulation, which demonstrates the blockade of autophagic flux. Fourthly, lysosomal impairments including alkalization and decrease of lysosomal membrane stability were observed in AgNP-treated THP-1 cells. In conclusion, we demonstrate that the impedance of monocyte-macrophage differentiation by AgNPs is mediated by autophagy blockade and lysosomal dysfunction. Our results suggest that crosstalk exists in different biological effects induced by AgNPs.

Effects of Feeder Cells on Dopaminergic Differentiation of Human Embryonic Stem Cells

PubMed Central

Zhao, Zhenqiang; Ma, Yanlin; Chen, Zhibin; Liu, Qian; Li, Qi; Kong, Deyan; Yuan, Kunxiong; Hu, Lan; Wang, Tan; Chen, Xiaowu; Peng, Yanan; Jiang, Weimin; Yu, Yanhong; Liu, Xinfeng

2016-01-01

Mouse embryonic fibroblasts (MEFs) and human foreskin fibroblasts (HFFs) are used for the culture of human embryonic stem cells (hESCs). MEFs and HFFs differed in their capacity to support the proliferation and pluripotency of hESCs and could affect cardiac differentiation potential of hESCs. The aim of this study was to evaluate the effect of MEFs and HFFs feeders on dopaminergic differentiation of hESCs lines. To minimize the impact of culture condition variation, two hESCs lines were cultured on mixed feeder cells (MFCs, MEFs: HFFs = 1:1) and HFFs feeder, respectively, and then were differentiated into dopaminergic (DA) neurons under the identical protocol. Dopaminergic differentiation was evaluated by immunocytochemistry, quantitative fluorescent real-time PCR, transmission and scanning electron microscopy, and patch clamp. Our results demonstrated that these hESCs-derived neurons were genuine and functional DA neurons. However, compared to hESCs line on MFCs feeder, hESCs line on HFFs feeder had a higher proportion of tyrosine hydroxylase (TH) positive cells and expressed higher levels of FOXA2, PITX3, NURR1, and TH genes. In addition, the values of threshold intensity and threshold membrane potential of DA neurons from hESCs line on HFFs feeder were lower than those of DA neurons from hESCs line on the MFCs feeder. In conclusion, HFFs feeder not only facilitated the differentiation of hESCs cells into dopaminergic neurons, but also induced hESCs-derived DA neurons to express higher electrophysiological excitability. Therefore, feeder cells could affect not only dopaminergic differentiation potential of different hESCs lines, but also electrophysiological properties of hESCs-derived DA neurons. PMID:28066186

The effect of differential training-based occupational therapy on hand and arm function in patients after stroke: Results of the pilot study.

PubMed

Repšaitė, Viktorija; Vainoras, Alfonsas; Berškienė, Kristina; Baltaduonienė, Daiva; Daunoravičienė, Algė; Sendžikaitė, Ernesta

2015-01-01

The aim of this study was to evaluate the effect of differential training-based occupational therapy on the recovery of arm function and to compare these data with the results obtained after conventional occupational therapy. A total of 27 patients who had suffered a cerebral infarction in the left brain hemisphere were recruited for the study. There were 9 men (33.33%) and 18 women (66.67%). All the patients had paresis of the right arm. The patients were divided into 2 groups: the control group comprised 15 patients who were given conventional occupational therapy (5 times per week) and the study group consisted of 12 patients who underwent conventional occupational therapy (3 times per week) along with occupational therapy based on differential training (2 times per week). In the control group, the mean performance time of only 2 tasks, i.e., flip cards and fold towel, improved significantly (P<0.05), while significant deterioration in the mean performance time of the task "lift can" was observed (P<0.05). In the study group, the mean performance time of all the tasks except for forearm to box (side), hand to box (front), and lift paperclip improved significantly (P<0.05), and no deterioration in arm function was observed. Both patients' groups improved arm function after occupational therapy sessions, but the patients who underwent conventional occupational therapy along with differential training-based occupational therapy recovered their arm function more effectively than their counterparts after conventional occupational therapy. Copyright © 2015 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Effects of Aminoglycoside Antibiotics on Human Embryonic Stem Cell Viability during Differentiation In Vitro

PubMed Central

Varghese, Divya S.; Parween, Shama; Ardah, Mustafa T.; Emerald, Bright Starling

2017-01-01

Human embryonic stem cells (hESCs) are being used extensively in array of studies to understand different mechanisms such as early human embryogenesis, drug toxicity testing, disease modeling, and cell replacement therapy. The protocols for the directed differentiation of hESCs towards specific cell types often require long-term cell cultures. To avoid bacterial contamination, these protocols include addition of antibiotics such as pen-strep and gentamicin. Although aminoglycosides, streptomycin, and gentamicin have been shown to cause cytotoxicity in various animal models, the effect of these antibiotics on hESCs is not clear. In this study, we found that antibiotics, pen-strep, and gentamicin did not affect hESC cell viability or expression of pluripotency markers. However, during directed differentiation towards neural and hepatic fate, significant cell death was noted through the activation of caspase cascade. Also, the expression of neural progenitor markers Pax6, Emx2, Otx2, and Pou3f2 was significantly reduced suggesting that gentamicin may adversely affect early embryonic neurogenesis whereas no effect was seen on the expression of endoderm or hepatic markers during differentiation. Our results suggest that the use of antibiotics in cell culture media for the maintenance and differentiation of hESCs needs thorough investigation before use to avoid erroneous results. PMID:29147115

Negative differential transconductance in silicon quantum well metal-oxide-semiconductor field effect/bipolar hybrid transistors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Naquin, Clint; Lee, Mark; Edwards, Hal

2014-11-24

Introducing explicit quantum transport into Si transistors in a manner amenable to industrial fabrication has proven challenging. Hybrid field-effect/bipolar Si transistors fabricated on an industrial 45 nm process line are shown to demonstrate explicit quantum transport signatures. These transistors incorporate a lateral ion implantation-defined quantum well (QW) whose potential depth is controlled by a gate voltage (V{sub G}). Quantum transport in the form of negative differential transconductance (NDTC) is observed to temperatures >200 K. The NDTC is tied to a non-monotonic dependence of bipolar current gain on V{sub G} that reduces drain-source current through the QW. These devices establish the feasibility ofmore » exploiting quantum transport to transform the performance horizons of Si devices fabricated in an industrially scalable manner.« less

Nonlinear current-voltage characteristics and enhanced negative differential conductance in graphene field effect transistors.

PubMed

Wang, Lin; Chen, Xiaoshuang; Hu, Yibin; Yu, Anqi; Lu, Wei

2014-11-07

Recent observations of the negative differential conductance (NDC) phenomenon in graphene field-effect transistors (FET) open up new opportunities for their application in graphene-based fast switches, frequency multipliers and, most importantly, in high frequency oscillators up to the terahertz regime. Unlike conventional two-terminal NDC devices that rely on resonant tunneling and inter-valley transferring, in the present work, it has been shown that the universal NDC phenomenon of graphene-based FETs originates from their intrinsic nonlinear carrier transport under a strong electric field. The operation of graphene-NDC devices depends strongly on the interface between graphene and dielectric materials, the scattering-limited carrier mobility, and on the saturation velocity. To reveal such NDC behavior, the output characteristics of GFET are investigated rigorously, with both an analytical model and self-consistent transport equation, and with a multi-electrical parameter simulation. It is demonstrated that the contact-induced doping effect plays an important role in the operational efficiency of graphene-based NDC devices, rather than the ambipolar behavior associated with the competition between electron and hole conductances. In the absence of a NDC regime or beyond one, ambipolar transport starts at Vds > 2Vgs at the drain end, and as the dielectric layer begins to thin down, the kink-like saturation output characteristic is enhanced by the quantum capacitance contribution. These observations reveal the intrinsic mechanism of the NDC effect and open up new opportunities for the performance improvement of GFETs in future high-frequency applications, beyond the current paradigm based on two-terminal diodes.

The effect of myotonic dystrophy transcript levels and location on muscle differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mastroyiannopoulos, Nikolaos P.; Chrysanthou, Elina; Kyriakides, Tassos C.

2008-12-12

In myotonic dystrophy type I (DM1), nuclear retention of mutant DMPK transcripts compromises muscle cell differentiation. Although several reports have identified molecular defects in myogenesis, it remains still unclear how exactly the retention of the mutant transcripts induces this defect. We have recently created a novel cellular model in which the mutant DMPK 3' UTR transcripts were released to the cytoplasm of myoblasts by using the WPRE genetic element. As a result, muscle cell differentiation was repaired. In this paper, this cellular model was further exploited to investigate the effect of the levels and location of the mutant transcripts onmore » muscle differentiation. Results show that the levels of these transcripts were proportional to the inhibition of both the initial fusion of myoblasts and the maturity of myotubes. Moreover, the cytoplasmic export of the mutant RNAs to the cytoplasm caused less inhibition only in the initial fusion of myoblasts.« less

Differential-Mode Biosensor Using Dual Extended-Gate Metal-Oxide-Semiconductor Field-Effect Transistors

NASA Astrophysics Data System (ADS)

Choi, Jinhyeon; Lee, Hee Ho; Ahn, Jungil; Seo, Sang-Ho; Shin, Jang-Kyoo

2012-06-01

In this paper, we present a differential-mode biosensor using dual extended-gate metal-oxide-semiconductor field-effect transistors (MOSFETs), which possesses the advantages of both the extended-gate structure and the differential-mode operation. The extended-gate MOSFET was fabricated using a 0.6 µm standard complementary metal oxide semiconductor (CMOS) process. The Au extended gate is the sensing gate on which biomolecules are immobilized, while the Pt extended gate is the dummy gate for use in the differential-mode detection circuit. The differential-mode operation offers many advantages such as insensitivity to the variation of temperature and light, as well as low noise. The outputs were measured using a semiconductor parameter analyzer in a phosphate buffered saline (PBS; pH 7.4) solution. A standard Ag/AgCl reference electrode was used to apply the gate bias. We measured the variation of output voltage with time, temperature, and light intensity. The bindings of self-assembled monolayer (SAM), streptavidin, and biotin caused a variation in the output voltage of the differential-mode detection circuit and this was confirmed by surface plasmon resonance (SPR) experiment. Biotin molecules could be detected up to a concentration of as low as 0.001 µg/ml.

TSH Receptor Function Is Required for Normal Thyroid Differentiation in Zebrafish

PubMed Central

Opitz, Robert; Maquet, Emilie; Zoenen, Maxime; Dadhich, Rajesh

2011-01-01

TSH is the primary physiological regulator of thyroid gland function. The effects of TSH on thyroid cells are mediated via activation of its membrane receptor [TSH receptor (TSHR)]. In this study, we examined functional thyroid differentiation in zebrafish and characterized the role of TSHR signaling during thyroid organogenesis. Cloning of a cDNA encoding zebrafish Tshr showed conservation of primary structure and functional properties between zebrafish and mammalian TSHR. In situ hybridization confirmed that the thyroid is the major site of tshr expression during zebrafish development. In addition, we identified tpo, iyd, duox, and duoxa as novel thyroid differentiation markers in zebrafish. Temporal analyses of differentiation marker expression demonstrated the induction of an early thyroid differentiation program along with thyroid budding, followed by a delayed onset of duox and duoxa expression coincident with thyroid hormone synthesis. Furthermore, comparative analyses in mouse and zebrafish revealed for the first time a thyroid-enriched expression of cell death regulators of the B-cell lymphoma 2 family during early thyroid morphogenesis. Knockdown of tshr function by morpholino microinjection into embryos did not affect early thyroid morphogenesis but caused defects in later functional differentiation. The thyroid phenotype observed in tshr morphants at later stages comprised a reduction in number and size of functional follicles, down-regulation of differentiation markers, as well as reduced thyroid transcription factor expression. A comparison of our results with phenotypes observed in mouse models of defective TSHR and cAMP signaling highlights the value of zebrafish as a model to enhance the understanding of functional differentiation in the vertebrate thyroid. PMID:21737742

The Effect of the Developed Differentiation Approach on the Achievements of the Students

ERIC Educational Resources Information Center

Altintas, Esra; Özdemir, Ahmet S.

2015-01-01

Problem Statement: The present study is of importance for designing a differentiation approach, which enables gifted students to use their present potential in mathematics effectively and enables them to develop their achievement, while looking at the effect of the approach on both gifted and non-gifted students. Within the scope of the developed…

Effects of non-steroidal anti-inflammatory drugs on proliferation, differentiation and migration in equine mesenchymal stem cells.

PubMed

Müller, Maike; Raabe, Oksana; Addicks, Klaus; Wenisch, Sabine; Arnhold, Stefan

2011-03-01

In equine medicine, stem cell therapies for orthopaedic diseases are routinely accompanied by application of NSAIDs (non-steroidal anti-inflammatory drugs). Thus, it has to be analysed how NSAIDs actually affect the growth and differentiation potential of MSCs (mesenchymal stem cells) in vitro in order to predict the influence of NSAIDs such as phenylbutazone, meloxicam, celecoxib and flunixin on MSCs after grafting in vivo. The effects of NSAIDs were evaluated regarding cell viability and proliferation. Additionally, the multilineage differentiation capacity and cell migration was analysed. NSAIDs at lower concentrations (0.1-1 μM for celecoxib and meloxicam and 10-50 μM for flunixin) exert a positive effect on cell proliferation and migration, while at higher concentrations (10-200 μM for celecoxib and meloxicam and 100-1000 μM for flunixin and phenylbutazone), there is rather a negative influence. While there is hardly any influence on the adipogenic as well as on the chondrogenic MSC differentiation, the osteogenic differentiation potential, as demonstrated with the von Kossa staining, is significantly disturbed. Thus, it can be concluded that the effects of NSAIDs on MSCs are largely dependent on the concentrations used. Additionally, for some differentiation lineages, also the choice of NSAID is critical.

Differential effect of visual motion adaption upon visual cortical excitability.

PubMed

Lubeck, Astrid J A; Van Ombergen, Angelique; Ahmad, Hena; Bos, Jelte E; Wuyts, Floris L; Bronstein, Adolfo M; Arshad, Qadeer

2017-03-01

The objectives of this study were 1 ) to probe the effects of visual motion adaptation on early visual and V5/MT cortical excitability and 2 ) to investigate whether changes in cortical excitability following visual motion adaptation are related to the degree of visual dependency, i.e., an overreliance on visual cues compared with vestibular or proprioceptive cues. Participants were exposed to a roll motion visual stimulus before, during, and after visual motion adaptation. At these stages, 20 transcranial magnetic stimulation (TMS) pulses at phosphene threshold values were applied over early visual and V5/MT cortical areas from which the probability of eliciting a phosphene was calculated. Before and after adaptation, participants aligned the subjective visual vertical in front of the roll motion stimulus as a marker of visual dependency. During adaptation, early visual cortex excitability decreased whereas V5/MT excitability increased. After adaptation, both early visual and V5/MT excitability were increased. The roll motion-induced tilt of the subjective visual vertical (visual dependence) was not influenced by visual motion adaptation and did not correlate with phosphene threshold or visual cortex excitability. We conclude that early visual and V5/MT cortical excitability is differentially affected by visual motion adaptation. Furthermore, excitability in the early or late visual cortex is not associated with an increase in visual reliance during spatial orientation. Our findings complement earlier studies that have probed visual cortical excitability following motion adaptation and highlight the differential role of the early visual cortex and V5/MT in visual motion processing. NEW & NOTEWORTHY We examined the influence of visual motion adaptation on visual cortex excitability and found a differential effect in V1/V2 compared with V5/MT. Changes in visual excitability following motion adaptation were not related to the degree of an individual's visual

The Effect of Mechanical Stimulation on Mineralization in Differentiating Osteoblasts in Collagen-I Scaffolds

PubMed Central

Damaraju, Swathi; Matyas, John R.; Rancourt, Derrick E.

2014-01-01

Developing a viable and functional bone scaffold in vitro that is capable of surviving and bearing mechanical load in vivo requires an understanding of the cell biology of osteoprogenitor cells, particularly how they are influenced by mechanical stimulation during cell differentiation and maturation. In this study, mechanical load was applied using a modified FlexCell plate to impart confined compression to collagen-I scaffolds seeded with undifferentiated murine embryonic stem cells. The activity, presence, and expression of osteoblast-cadherin (OB-Cad) and connexin-43, as well as various pluripotent and osteogenic markers were examined at 5–30 days of differentiation as cells were stimulated to differentiate to osteoblasts with and without applied mechanical load. Fluorescence recovery after photobleaching, immunofluorescence, viability, von Kossa, and real-time polymerase chain reaction assessments revealed that mechanical prestimulation of this cell-seeded scaffold altered the expression of OB-Cad and connexin-43 and resulted in significant differences in the structure and organization of mineralization present in the collagen matrix. Specifically, cells in gels that were loaded for 40 h after 5 days of differentiation and then left to fully differentiate for 30 days produced a highly structured honeycomb-shaped mineralization in the matrix; an outcome that was previously shown to be indicative of late osteoblast/early osteocyte activity. This study highlights the potential of mechanical load to accelerate differentiation and enhance osteoblast communication and function during the differentiation process, and highlights a time point of cell differentiation within this scaffold to apply load in order to most effectively transduce a mechanical signal. PMID:24851936

Differential Effect of MyD88 Signal in Donor T Cells on Graft-versus-Leukemia Effect and Graft-versus-Host Disease after Experimental Allogeneic Stem Cell Transplantation.

PubMed

Lim, Ji-Young; Ryu, Da-Bin; Lee, Sung-Eun; Park, Gyeongsin; Choi, Eun Young; Min, Chang-Ki

2015-11-01

Despite the presence of toll like receptor (TLR) expression in conventional TCRαβ T cells, the direct role of TLR signaling via myeloid differentiation factor 88 (MyD88) within T lymphocytes on graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after allogeneic stem cell transplantation (allo-SCT) remains unknown. In the allo-SCT model of C57BL/6 (H-2(b)) → B6D2F1 (H-2(b/d)), recipients received transplants of wild type (WT) T-cell-depleted (TCD) bone marrow (BM) and splenic T cells from either WT or MyD88 deficient (MyD88KO) donors. Host-type (H-2(d)) P815 mastocytoma or L1210 leukemia cells were injected either subcutaneously or intravenously to generate a GVHD/GVL model. Allogeneic recipients of MyD88KO T cells demonstrated a greater tumor growth without attenuation of GVHD severity. Moreover, GVHD-induced GVL effect, caused by increasing the conditioning intensity was also not observed in the recipients of MyD88KO T cells. In vitro, the absence of MyD88 in T cells resulted in defective cytolytic activity to tumor targets with reduced ability to produce IFN-γ or granzyme B, which are known to critical for the GVL effect. However, donor T cell expansion with effector and memory T-cell differentiation were more enhanced in GVHD hosts of MyD88KO T cells. Recipients of MyD88KO T cells experienced greater expansion of Foxp3- and IL4-expressing T cells with reduced INF-γ producing T cells in the spleen and tumor-draining lymph nodes early after transplantation. Taken together, these results highlight a differential role for MyD88 deficiency on donor T-cells, with decreased GVL effect without attenuation of the GVHD severity after experimental allo-SCT.

Spectrally resolved interferometric observations of α Cephei and physical modeling of fast rotating stars

NASA Astrophysics Data System (ADS)

Delaa, O.; Zorec, J.; Domiciano de Souza, A.; Mourard, D.; Perraut, K.; Stee, Ph.; Frémat, Y.; Monnier, J.; Kraus, S.; Che, X.; Bério, Ph.; Bonneau, D.; Clausse, J. M.; Challouf, M.; Ligi, R.; Meilland, A.; Nardetto, N.; Spang, A.; McAlister, H.; ten Brummelaar, T.; Sturmann, J.; Sturmann, L.; Turner, N.; Farrington, C.; Goldfinger, P. J.

2013-07-01

Context. When a given observational quantity depends on several stellar physical parameters, it is generally very difficult to obtain observational constraints for each of them individually. Therefore, we studied under which conditions constraints for some individual parameters can be achieved for fast rotators, knowing that their geometry is modified by the rapid rotation which causes a non-uniform surface brightness distribution. Aims: We aim to study the sensitivity of interferometric observables on the position angle of the rotation axis (PA) of a rapidly rotating star, and whether other physical parameters can influence the determination of PA, and also the influence of the surface differential rotation on the determination of the β exponent in the gravity darkening law that enters the interpretation of interferometric observations, using α Cep as a test star. Methods: We used differential phases obtained from observations carried out in the Hα absorption line of α Cep with the VEGA/CHARA interferometer at high spectral resolution, R = 30 000 to study the kinematics in the atmosphere of the star. Results: We studied the influence of the gravity darkening effect (GDE) on the determination of the PA of the rotation axis of α Cep and determined its value, PA = -157-10°+17°. We conclude that the GDE has a weak influence on the dispersed phases. We showed that the surface differential rotation can have a rather strong influence on the determination of the gravity darkening exponent. A new method of determining the inclination angle of the stellar rotational axis is suggested. We conclude that differential phases obtained with spectro-interferometry carried out on the Hα line can in principle lead to an estimate of the stellar inclination angle i. However, to determine both i and the differential rotation parameter α, lines free from the Stark effect and that have collision-dominated source functions are to be preferred.

On Orders of Observables on Effect Algebras

NASA Astrophysics Data System (ADS)

Dvurečenskij, Anatolij

2017-12-01

On the set of bounded observables on an effect algebra, the Olson order defined by spectral resolutions and the standard order defined by a system of σ-additive states are introduced. We show that sharp bounded observables form a Dedekind σ-complete sublattice of a Dedekind complete lattice under the Olson order. In addition, we compare both orders, and we illustrate them on different effect algebras.

Directing the osteoblastic and chondrocytic differentiations of mesenchymal stem cells: matrix vs. induction media

PubMed Central

He, Jing; Guo, Jianglong; Jiang, Bo; Yao, Ruijuan; Wu, Yao

2017-01-01

Abstract While both induction culture media and matrix have been reported to regulate the stem cell fate, little is known about which factor plays a more decisive role in directing the MSC differentiation lineage as well as the underlying mechanisms. To this aim, we seeded MSCs on HA-collagen and HA-synthetic hydrogel matrixes, which had demonstrated highly different potentials toward osteoblastic and chondrocytic differentiation lineages, respectively, and cultured them with osteogenic, chondrogenic and normal culture media, respectively. A systematic comparison has been carried out on the effects of induction media and matrix on MSC adhesion, cytoskeleton organization, proliferation, and in particular differentiation into the osteoblastic and chondrocytic lineages. The results demonstrated that the matrix selection had a much more profound effect on directing the differentiation lineage than the induction media did. The strong modulation effect on the transcription activities might be the critical factor contributing to the above observations in our study, where canonical Wnt-β-Catenin signal pathway was directly involved in the matrix-driven osteoblastic differentiation. Such findings not only provide a critical insight on natural cellular events leading to the osteoblastic and chondrocytic differentiations, but also have important implications in biomaterial design for tissue engineering applications. PMID:29026640

Differential modulation of the discriminative stimulus effects of methamphetamine and cocaine by alprazolam and oxazepam in male and female rats.

PubMed

Spence, A L; Guerin, G F; Goeders, N E

2016-03-01

Drug users often combine benzodiazepines with psychostimulants, such as methamphetamine. However, very little research has been conducted on this type of polydrug use, particularly in female subjects. The present study was therefore designed to examine the effects of two benzodiazepines, alprazolam and oxazepam, on the discriminative stimulus effects of methamphetamine and cocaine in both male and female rats. Rats were trained to discriminate methamphetamine (1.0 mg/kg, ip) or cocaine (10 mg/kg, ip) from saline using a two-lever operant, food-reinforced, drug discrimination design. Pretreatment with oxazepam (5, 10 and 20 mg/kg, ip) significantly attenuated methamphetamine discrimination in both male and female rats. In contrast, however, the high dose of alprazolam (4 mg/kg, ip) actually augmented the subjective effects of lower doses of methamphetamine (0.125 and 0.25 mg/kg, ip). Oxazepam produced similar effects on the subjective effects of cocaine as with methamphetamine, significantly reducing cocaine discrimination in both male and female rats. However, neither the high nor low dose of alprazolam (2 and 4 mg/kg, ip) produced any apparent effect on cocaine discrimination. Finally, while similar results were observed in both male and female rats across these experiments, methamphetamine and cocaine discrimination were more sensitive to oxazepam in female subjects. The results of these experiments suggest that alprazolam and oxazepam can differentially affect the subjective effects of methamphetamine and cocaine. These results also demonstrate that alprazolam can differentially affect the discriminative stimulus effects of methamphetamine and cocaine. Copyright © 2015 Elsevier Ltd. All rights reserved.

An in vivo model fish system to test chemical effects on sexual differentiation and development: exposure to ethinyl estradiol

USGS Publications Warehouse

Papoulias, Diana M.; Noltie, Douglas B.; Tillitt, Donald E.

2000-01-01

A model system was characterized which may be used as an in vivo screen for effects of chemicals or environmental mixtures on sexual differentiation and development of reproductive organs and gametes. We evaluated the effects of a model environmental estrogen, ethinyl estradiol (EE2), on the d-rR strain of medaka, Oryzias latipes, using a nano-injection exposure. Gonad histopathology indicated that a single injection of 0.5–2.5 ng EE2/egg can cause phenotypic sex-reversal of genetic males to females. Sex-reversals could be detected as early as 7 days post-hatch. Sex-reversed males had female-typical duct development and the secondary sex characteristics we measured were generally consistent with phenotype, with the exception of a few EE2-exposed XX and XY females which possessed ambiguous anal fins. Using discriminant analysis, we determined that the presence or absence of the secondary sex characteristic, a dorsal fin notch, was a very reliable indicator of gonadal sex. No instances of gonadal intersexes were observed. Ethinyl estradiol also appeared to reduce growth but not condition (weight-at-length) and exposed XX females appeared to have a higher incidence of atretic follicles relative to controls. Our results suggest that estrogenic chemicals may influence sexual differentiation and development and that the medaka model is well suited to assessing these effects.

Effect of space relevant radiation exposure on differentiation and mineralization of murine osteoprogenitor cells

NASA Astrophysics Data System (ADS)

Lau, Patrick; Hu, Yueyuan; Hellweg, Christine; Baumstark-Khan, Christa; Reitz, Guenther

Extended exposure to altered gravity conditions like during long-term space flight results in significant bone loss. Exposure to ionizing radiation for cancer therapy causes bone damage and may increase the risk of fractures. Similarly, besides altered gravity conditions, astronauts on exploratory missions beyond low-Earth orbit will be exposed to high-energy heavy ions in addition to proton and photon radiation, although for prolonged periods and at lower doses and dose rates compared with therapy. Space conditions may place astronauts at a greater risk for mission-critical fractures. Until now, little is known about the effects of space radiation on the skeletal system especially on osteoprogenitor cells. Accelerator facilities are used to simulate parts of the radiation environment in space. Heavy ion accelerators therefore could be used to assess radiation risks for astronauts who will be exposed to higher radiation doses e.g. on a Mars mission. The aim of the present study was to determine the biological effects of spaceflight-relevant radiation exposure on the cellular level using murine osteoprogenitor cell lines compared to nonirradiated controls. To gain a deeper understanding of bone cell differenti-ation and mineralization after exposure to heavy ions, we examined gene expression modulation of bone specific transcription factors, osteoblast specific marker genes as well as genes function as coupling factors that link bone resorption to bone formation. We investigated the transcrip-tional modulation of type I collagen (Col I), osteocalcin (Ocn), Transforming growth factor-β1 (TGF-β1), interleukin-6 (IL-6) and the bone specific transcription factor Runx2 (Cbfa1). To gain deeper insight into potential cellular mechanisms involved in cellular response after ex-posure to heavy ions, we investigated gene expression modulations after exposure to energetic carbon ions (35 MeV/u, 73.2 keV/µm), iron ions (1000 MeV/u, 150 keV/µm) and lead ions (29 MeV/u, 9600

The Differential Effects of Rape Prevention Programming on Attitudes, Behavior, and Knowledge.

ERIC Educational Resources Information Center

Heppner, Mary J.; And Others

1995-01-01

Evaluates whether type of programming differentially affects the processing of rape prevention messages, attitudes, knowledge, behaviors, and stability of change. Participants (n=258) were assigned to a didactic-video program, an interactive drama, or control. Results indicated that the interactive video was most effective in central route…

Cell differentiation modeled via a coupled two-switch regulatory network

NASA Astrophysics Data System (ADS)

Schittler, D.; Hasenauer, J.; Allgöwer, F.; Waldherr, S.

2010-12-01

Mesenchymal stem cells can give rise to bone and other tissue cells, but their differentiation still escapes full control. In this paper we address this issue by mathematical modeling. We present a model for a genetic switch determining the cell fate of progenitor cells which can differentiate into osteoblasts (bone cells) or chondrocytes (cartilage cells). The model consists of two switch mechanisms and reproduces the experimentally observed three stable equilibrium states: a progenitor, an osteogenic, and a chondrogenic state. Conventionally, the loss of an intermediate (progenitor) state and the entailed attraction to one of two opposite (differentiated) states is modeled as a result of changing parameters. In our model in contrast, we achieve this by distributing the differentiation process to two functional switch parts acting in concert: one triggering differentiation and the other determining cell fate. Via stability and bifurcation analysis, we investigate the effects of biochemical stimuli associated with different system inputs. We employ our model to generate differentiation scenarios on the single cell as well as on the cell population level. The single cell scenarios allow to reconstruct the switching upon extrinsic signals, whereas the cell population scenarios provide a framework to identify the impact of intrinsic properties and the limiting factors for successful differentiation.

Thin Film Differential Photosensor for Reduction of Temperature Effects in Lab-on-Chip Applications.

PubMed

de Cesare, Giampiero; Carpentiero, Matteo; Nascetti, Augusto; Caputo, Domenico

2016-02-20

This paper presents a thin film structure suitable for low-level radiation measurements in lab-on-chip systems that are subject to thermal treatments of the analyte and/or to large temperature variations. The device is the series connection of two amorphous silicon/amorphous silicon carbide heterojunctions designed to perform differential current measurements. The two diodes experience the same temperature, while only one is exposed to the incident radiation. Under these conditions, temperature and light are the common and differential mode signals, respectively. A proper electrical connection reads the differential current of the two diodes (ideally the photocurrent) as the output signal. The experimental characterization shows the benefits of the differential structure in minimizing the temperature effects with respect to a single diode operation. In particular, when the temperature varies from 23 to 50 °C, the proposed device shows a common mode rejection ratio up to 24 dB and reduces of a factor of three the error in detecting very low-intensity light signals.

Intergenerational effects of shifts in women's educational distribution in South Korea: Transmission, differential fertility, and assortative mating.

PubMed

Kye, Bongoh; Mare, Robert D

2012-11-01

This study examines the intergenerational effects of changes in women's education in South Korea. We define intergenerational effects as changes in the distribution of educational attainment in an offspring generation associated with the changes in a parental generation. Departing from the previous approach in research on social mobility that has focused on intergenerational association, we examine the changes in the distribution of educational attainment across generations. Using a simulation method based on Mare and Maralani's recursive population renewal model, we examine how intergenerational transmission, assortative mating, and differential fertility influence intergenerational effects. The results point to the following conclusions. First, we find a positive intergenerational effect: improvement in women's education leads to improvement in daughter's education. Second, we find that the magnitude of intergenerational effects substantially depends on assortative marriage and differential fertility: assortative mating amplifies and differential fertility dampens the intergenerational effects. Third, intergenerational effects become bigger for the less educated and smaller for the better educated over time, which is a consequence of educational expansion. We compare our results with Mare and Maralani's original Indonesian study to illustrate how the model of intergenerational effects works in different socioeconomic circumstances. Copyright © 2012 Elsevier Inc. All rights reserved.

Intergenerational effects of shifts in women's educational distribution in South Korea: Transmission, differential fertility, and assortative mating

PubMed Central

Kye, Bongoh; Mare, Robert D.

2014-01-01

This study examines the intergenerational effects of changes in women's education in South Korea. We define intergenerational effects as changes in the distribution of educational attainment in an offspring generation associated with the changes in a parental generation. Departing from the previous approach in research on social mobility that has focused on intergenerational association, we examine the changes in the distribution of educational attainment across generations. Using a simulation method based on Mare and Maralani's recursive population renewal model, we examine how intergenerational transmission, assortative mating, and differential fertility influence intergenerational effects. The results point to the following conclusions. First, we find a positive intergenerational effect: improvement in women's education leads to improvement in daughter's education. Second, we find that the magnitude of intergenerational effects substantially depends on assortative marriage and differential fertility: assortative mating amplifies and differential fertility dampens the intergenerational effects. Third, intergenerational effects become bigger for the less educated and smaller for the better educated over time, which is a consequence of educational expansion. We compare our results with Mare and Maralani's original Indonesian study to illustrate how the model of intergenerational effects works in different socioeconomic circumstances. PMID:23017970

Selective neuronal differentiation of neural stem cells induced by nanosecond microplasma agitation.

PubMed

Xiong, Z; Zhao, S; Mao, X; Lu, X; He, G; Yang, G; Chen, M; Ishaq, M; Ostrikov, K

2014-03-01

An essential step for therapeutic and research applications of stem cells is their ability to differentiate into specific cell types. Neuronal cells are of great interest for medical treatment of neurodegenerative diseases and traumatic injuries of central nervous system (CNS), but efforts to produce these cells have been met with only modest success. In an attempt of finding new approaches, atmospheric-pressure room-temperature microplasma jets (MPJs) are shown to effectively direct in vitro differentiation of neural stem cells (NSCs) predominantly into neuronal lineage. Murine neural stem cells (C17.2-NSCs) treated with MPJs exhibit rapid proliferation and differentiation with longer neurites and cell bodies eventually forming neuronal networks. MPJs regulate ~75% of NSCs to differentiate into neurons, which is a higher efficiency compared to common protein- and growth factors-based differentiation. NSCs exposure to quantized and transient (~150 ns) micro-plasma bullets up-regulates expression of different cell lineage markers as β-Tubulin III (for neurons) and O4 (for oligodendrocytes), while the expression of GFAP (for astrocytes) remains unchanged, as evidenced by quantitative PCR, immunofluorescence microscopy and Western Blot assay. It is shown that the plasma-increased nitric oxide (NO) production is a factor in the fate choice and differentiation of NSCs followed by axonal growth. The differentiated NSC cells matured and produced mostly cholinergic and motor neuronal progeny. It is also demonstrated that exposure of primary rat NSCs to the microplasma leads to quite similar differentiation effects. This suggests that the observed effect may potentially be generic and applicable to other types of neural progenitor cells. The application of this new in vitro strategy to selectively differentiate NSCs into neurons represents a step towards reproducible and efficient production of the desired NSC derivatives. Published by Elsevier B.V.

Design of an Auto-zeroed, Differential, Organic Thin-film Field-effect Transistor Amplifier for Sensor Applications

NASA Technical Reports Server (NTRS)

Binkley, David M.; Verma, Nikhil; Crawford, Robert L.; Brandon, Erik; Jackson, Thomas N.

2004-01-01

Organic strain gauge and other sensors require high-gain, precision dc amplification to process their low-level output signals. Ideally, amplifiers would be fabricated using organic thin-film field-effect transistors (OTFT's) adjacent to the sensors. However, OTFT amplifiers exhibit low gain and high input-referred dc offsets that must be effectively managed. This paper presents a four-stage, cascaded differential OTFT amplifier utilizing switched capacitor auto-zeroing. Each stage provides a nominal voltage gain of four through a differential pair driving low-impedance active loads, which provide common-mode output voltage control. p-type pentacence OTFT's are used for the amplifier devices and auto-zero switches. Simulations indicate the amplifier provides a nominal voltage gain of 280 V/V and effectively amplifies a 1-mV dc signal in the presence of 500-mV amplifier input-referred dc offset voltages. Future work could include the addition of digital gain calibration and offset correction of residual offsets associated with charge injection imbalance in the differential circuits.

Investigating the Differential Emission Measure and Energetics of Microflares with Combined SDO/AIA and RHESSI Observations

NASA Technical Reports Server (NTRS)

Inglis, A. R.; Christe, S.

2014-01-01

An important question in solar physics is whether solar microflares, the smallest currently observable flare events in X-rays, possess the same energetic properties as large flares. Recent surveys have suggested that microflares may be less efficient particle accelerators than large flares, and hence contribute less non-thermal energy, which may have implications for coronal heating mechanisms. We therefore explore the energetic properties of microflares by combining EUV and X-ray measurements. We present forward-fitting differential emission measure (DEM) analysis of 10 microflares. The fitting is constrained by combining, for the first time, high-temperature Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) observations and flux data from the Solar Dynamics Observatory (SDO) Atmospheric Imaging Assembly (AIA). Two fitting models are tested for the DEM; a Gaussian distribution and a uniform DEM profile. A Gaussian fit proved unable to explain the observations for any of the studied microflares. However, 8 of 10 events studied were reasonably fit by a uniform DEM profile. Hence microflare plasma can be considered to be significantly multi-thermal, and may not be significantly peaked or contain resolvable fine structure, within the uncertainties of the observational instruments. The thermal and non-thermal energy is estimated for each microflare, comparing the energy budget with an isothermal plasma assumption. From the multi-thermal fits the minimum non-thermal energy content was found to average approximately 30% of the estimated thermal energy. By comparison, under an isothermal model the non-thermal and thermal energy estimates were generally comparable. Hence, multi-thermal plasma is an important consideration for solar microflares that substantially alters their thermal and non-thermal energy content.

The Process of Horizontal Differentiation: Two Models.

ERIC Educational Resources Information Center

Daft, Richard L.; Bradshaw, Patricia J.

1980-01-01

Explores the process of horizontal differentiation by examining events leading to the establishment of 30 new departments in five universities. Two types of horizontal differentiation processes--administrative and academic--were observed and each was associated with different organizational conditions. (Author/IRT)

Parental Divorce and Family Functioning: Effects on Differentiation Levels of Young Adults.

ERIC Educational Resources Information Center

Johnson, Patrick; Throngren, Jill M.; Smith, Adina J.

2001-01-01

Study examines the effect of parental divorce and various dimensions of functioning in the family of origin on young adult development. Results indicate that parental divorce and family functioning significantly affect differentiation levels of young adults. Implications of the results for counselors and future researchers are provided. (Contains…

Differential Effects of Reinforcement on the Self-Monitoring of On-Task Behavior

ERIC Educational Resources Information Center

Otero, Tiffany L.; Haut, Jillian M.

2016-01-01

In the current study, the differential effects of reinforcement on a self-monitoring intervention were evaluated. Three students nominated by their teachers for having a marked difficultly maintaining on-task behaviors participated in the study. Using an alternating treatments single-case design to assess self-monitoring with and without…

For numerical differentiation, dimensionality can be a blessing!

NASA Astrophysics Data System (ADS)

Anderssen, Robert S.; Hegland, Markus

Finite difference methods, such as the mid-point rule, have been applied successfully to the numerical solution of ordinary and partial differential equations. If such formulas are applied to observational data, in order to determine derivatives, the results can be disastrous. The reason for this is that measurement errors, and even rounding errors in computer approximations, are strongly amplified in the differentiation process, especially if small step-sizes are chosen and higher derivatives are required. A number of authors have examined the use of various forms of averaging which allows the stable computation of low order derivatives from observational data. The size of the averaging set acts like a regularization parameter and has to be chosen as a function of the grid size h. In this paper, it is initially shown how first (and higher) order single-variate numerical differentiation of higher dimensional observational data can be stabilized with a reduced loss of accuracy than occurs for the corresponding differentiation of one-dimensional data. The result is then extended to the multivariate differentiation of higher dimensional data. The nature of the trade-off between convergence and stability is explicitly characterized, and the complexity of various implementations is examined.

Dynamics and heterogeneity of a fate determinant during transition towards cell differentiation

DOE PAGES

Pelaez, Nicolas; Gavalda-Miralles, Arnau; Wang, Bao; ...

2015-11-19

Yan is an ETS-domain transcription factor responsible for maintaining Drosophila eye cells in a multipotent state. Yan is at the core of a regulatory network that determines the time and place in which cells transit from multipotency to one of several differentiated lineages. Using a fluorescent reporter for Yan expression, we observed a biphasic distribution of Yan in multipotent cells, with a rapid inductive phase and slow decay phase. Transitions to various differentiated states occurred over the course of this dynamic process, suggesting that Yan expression level does not strongly determine cell potential. Consistent with this conclusion, perturbing Yan expressionmore » by varying gene dosage had no effect on cell fate transitions. However, we observed that as cells transited to differentiation, Yan expression became highly heterogeneous and this heterogeneity was transient. Signals received via the EGF Receptor were necessary for the transience in Yan noise since genetic loss caused sustained noise. As a result, since these signals are essential for eye cells to differentiate, we suggest that dynamic heterogeneity of Yan is a necessary element of the transition process, and cell states are stabilized through noise reduction.« less

Differential Effects of HRAS Mutation on LTP-Like Activity Induced by Different Protocols of Repetitive Transcranial Magnetic Stimulation.

PubMed

Dileone, Michele; Ranieri, Federico; Florio, Lucia; Capone, Fioravante; Musumeci, Gabriella; Leoni, Chiara; Mordillo-Mateos, Laura; Tartaglia, Marco; Zampino, Giuseppe; Di Lazzaro, Vincenzo

2016-01-01

Costello syndrome (CS) is a rare congenital disorder due to a G12S amino acid substitution in HRAS protoncogene. Previous studies have shown that Paired Associative Stimulation (PAS), a repetitive brain stimulation protocol inducing motor cortex plasticity by coupling peripheral nerve stimulation with brain stimulation, leads to an extremely pronounced motor cortex excitability increase in CS patients. Intermittent Theta Burst Stimulation (iTBS) represents a protocol able to induce motor cortex plasticity by trains of stimuli at 50 Hz. In healthy subjects PAS and iTBS produce similar after-effects in motor cortex excitability. Experimental models showed that HRAS-dependent signalling pathways differently affect LTP induced by different patterns of repetitive synaptic stimulation. We aimed to compare iTBS-induced after-effects on motor cortex excitability with those produced by PAS in CS patients and to observe whether HRAS mutation differentially affects two different forms of neuromodulation protocols. We evaluated in vivo after-effects induced by PAS and iTBS applied over the right motor cortex in 4 CS patients and in 21 healthy age-matched controls. Our findings confirmed HRAS-dependent extremely pronounced PAS-induced after-effects and showed for the first time that iTBS induces no change in MEP amplitude in CS patients whereas both protocols lead to an increase of about 50% in controls. CS patients are characterized by an impairment of iTBS-related LTP-like phenomena besides enhanced PAS-induced after-effects, suggesting that HRAS-dependent signalling pathways have a differential influence on PAS- and iTBS-induced plasticity in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

Determination of Differential Emission Measure Distribution of Coronal Structures Observed by SphinX During Recent Minimum of Solar Activity

NASA Astrophysics Data System (ADS)

Kepa, Anna; Gburek, Szymon; Siarkowski, Marek; Sylwester, Barbara; Sylwester, Janusz; Kowalinski, Miroslaw

SphinX is a high-sensitivity soft X-ray spectrophotometer which measures soft X-ray spectra in the energy range between 0.8 keV and 15 keV. From February to November 2009 the instrument has observed unusually quiet solar coronal emission as well as a number of weak solar flares. Based on SphinX spectra it is possible to study the differential emission measure distributions (DEM) in the temperature range roughly between 1 MK and 10 MK. The aim of the present study is to unveil DEM plasma distributions for selected activity conditions and analyze their variability.

Existence and stability of periodic solutions of an impulsive differential equation and application to CD8 T-cell differentiation.

PubMed

Girel, Simon; Crauste, Fabien

2018-06-01

Unequal partitioning of the molecular content at cell division has been shown to be a source of heterogeneity in a cell population. We propose to model this phenomenon with the help of a scalar, nonlinear impulsive differential equation (IDE). To study the effect of molecular partitioning at cell division on the effector/memory cell-fate decision in a CD8 T-cell lineage, we study an IDE describing the concentration of the protein Tbet in a CD8 T-cell, where impulses are associated to cell division. We discuss how the degree of asymmetry of molecular partitioning can affect the process of cell differentiation and the phenotypical heterogeneity of a cell population. We show that a moderate degree of asymmetry is necessary and sufficient to observe irreversible differentiation. We consider, in a second part, a general autonomous IDE with fixed times of impulse and a specific form of impulse function. We establish properties of the solutions of that equation, most of them obtained under the hypothesis that impulses occur periodically. In particular, we show how to investigate the existence of periodic solutions and their stability by studying the flow of an autonomous differential equation. Then we apply those properties to prove the results presented in the first part.

Complex effect of hydroxyapatite nanoparticles on the differentiation and functional activity of human pre-osteoclastic cells.

PubMed

Costa-Rodrigues, João; Silva, Ana; Santos, Catarina; Almeida, Maria Margarida; Costa, Maria Elisabete; Fernandes, Maria Helena

2014-12-01

Nanosized hydroxyapatite (HA) is a promising material in clinical applications targeting the bone tissue. NanoHA is able to modulate bone cellular events, which accounts for its potential utility, but also raises safety concerns regarding the maintenance of the bone homeostasis. This work analyses the effects of HA nanoparticles (HAnp) on osteoclastic differentiation and activity, an issue that has been barely addressed. Rod-like HAnp, produced by a hydrothermal precipitation method, were tested on peripheral blood mononuclear cells (PBMC), which contains the CD14+ osteoclastic precursors, in unstimulated or osteoclastogenic-induced conditions. HAnp were added at three time-points during the osteoclastic differentiation pathway, and cell response was evaluated for osteoclastic related parameters. Results showed that HAnp modulated the differentiation and function of osteoclastic cells in a dose- and time-dependent manner. In addition, the effects were dependent on the stage of osteoclastic differentiation. In unstimulated PBMC, HAnp significantly increased osteoclastogenesis, leading to the formation of mature osteoclasts, as evident by the significant increase of TRAP activity, number of TRAP-positive multinucleated cells, osteoclastic gene expression and resorbing ability. However, in a population of mature osteoclasts (formed in osteoclastogenic-induced PBMC cultures), HAnp caused a dose-dependent decrease on the osteoclastic-related parameters. These results highlight the complex effects of HAnp in osteoclastic differentiation and activity, and suggest the possibility of HAnp to modulate/disrupt osteoclastic behavior, with eventual imbalances in the bone metabolism. This should be carefully considered in bone-related and other established and prospective biomedical applications of HAnp.

The effect of low static magnetic field on osteogenic and adipogenic differentiation potential of human adipose stromal/stem cells

NASA Astrophysics Data System (ADS)

Marędziak, Monika; Śmieszek, Agnieszka; Tomaszewski, Krzysztof A.; Lewandowski, Daniel; Marycz, Krzysztof

2016-01-01

The aim of this work was to investigate the effects of static magnetic field (SMF) on the osteogenic properties of human adipose derived mesenchymal stem cells (hASCs). In this study in seven days viability assay we examined the impact of SMF on cells proliferation rate, population doubling time, and ability to form single-cell derived colonies. We have also examined cells' morphology, ultrastructure and osteogenic properties on the protein as well as mRNA level. We established a complex approach, which enabled us to obtain information about SMF and hASCs potential in the context of differentiation into osteogenic and adipogenic lineages. We demonstrated that SMF enhances both viability and osteogenic properties of hASCs through higher proliferation factor and shorter population doubling time. We have also observed asymmetrically positioned nuclei and organelles after SMF exposition. With regards to osteogenic properties we observed increased levels of osteogenic markers i.e. osteopontin, osteocalcin and increased ability to form osteonodules with positive reaction to Alizarin Red dye. We have also shown that SMF besides enhancing osteogenic properties of hASCs, simultaneously decreases their ability to differentiate into adipogenic lineage. Our results clearly show a direct influence of SMF on the osteogenic potential of hASCs. These results provide key insights into the role of SMF on their cellular fate and properties.

Iterative Purification and Effect Size Use with Logistic Regression for Differential Item Functioning Detection

ERIC Educational Resources Information Center

French, Brian F.; Maller, Susan J.

2007-01-01

Two unresolved implementation issues with logistic regression (LR) for differential item functioning (DIF) detection include ability purification and effect size use. Purification is suggested to control inaccuracies in DIF detection as a result of DIF items in the ability estimate. Additionally, effect size use may be beneficial in controlling…

The effect of observers on behavior and the brain during aggressive encounters.

PubMed

Desjardins, Julie K; Becker, Lisa; Fernald, Russell D

2015-10-01

What effect does an audience have on an animal's behavior and where is this influence registered in the brain? To answer these questions, we analyzed male cichlid fish fighting in the presence of audiences of various compositions and measured expression of immediate early genes in the brain as a proxy for neural activity. We hypothesized their behavior would change depending on who was watching them. We measured behavioral responses from both the "watchers" and the "watched" during aggressive encounters and found that males fighting in the presence of an audience were more aggressive than males fighting without an audience. Depending on the nature of the audience, immediate early gene expression in key brain nuclei was differentially influenced. Both when an audience of larger males watched fighting males, and when they were watching larger males fighting, nuclei in the brain considered homologous with mammalian nuclei known to be associated with anxiety showed increased activity. When males were in the presence of any audience or when males saw any other males fighting, nuclei in the brain known to be involved in reproduction and aggression were differentially activated relative to control animals. In all cases, there was a close relationship between patterns of brain gene expression between fighters and observers. This suggests that the network of brain regions known as the social behavior network, common across vertebrates, are activated not only in association with the expression of social behavior but also by the reception of social information. Copyright © 2015 Elsevier B.V. All rights reserved.

The effect of observers on behavior and the brain during aggressive encounters

PubMed Central

Desjardins, Julie K.; Becker, Lisa; Fernald, Russell D.

2015-01-01

What effect does an audience have on an animal’s behavior and where is this influence registered in the brain? To answer these questions, we analyzed male cichlid fish fighting in the presence of audiences of various compositions and measured expression of immediate early genes in the brain as a proxy for neural activity. We hypothesized their behavior would change depending on who was watching them. We measured behavioral responses from both the “watchers” and the “watched” during aggressive encounters and found that males fighting in the presence of an audience were more aggressive than males fighting without an audience. Depending on the nature of the audience, immediate early gene expression in key brain nuclei was differentially influenced. Both when an audience of larger males watched fighting males, and when they were watching larger males fighting, nuclei in the brain considered homologous with mammalian nuclei known to be associated with anxiety showed increased activity. When males were in the presence of any audience or when males saw any other males fighting, nuclei in the brain known to be involved in reproduction and aggression were differentially activated relative to control animals. In all cases, there was a close relationship between patterns of brain gene expression between fighters and observers. This suggests that the network of brain regions known as the social behavior network, common across vertebrates, are activated not only in association with the expression of social behavior but also by the reception of social information. PMID:26097004

The Unruh effect for eccentric uniformly rotating observers

NASA Astrophysics Data System (ADS)

Ramezani-Aval, H.

It is common to use Galilean rotational transformation (GRT) to investigate the Unruh effect for uniformly rotating observers. However, the rotating observer in this subject is an eccentric observer while GRT is only valid for centrally rotating observers. Thus, the reliability of the results of applying GRT to the study of the Unruh effect might be considered as questionable. In this work, the rotational analog of the Unruh effect is investigated by employing two relativistic rotational transformations corresponding to the eccentric rotating observer, and it is shown that in both cases, the detector response function is nonzero. It is also shown that although consecutive Lorentz transformations cannot give a frame within which the canonical construction can be carried out, the expectation value of particle number operator in canonical approach will be zero if we use modified Franklin transformation. These conclusions reinforce the claim that correspondence between vacuum states defined via canonical field theory and a detector is broken for rotating observers. Some previous conclusions are commented on and some controversies are also discussed.

Examination of the effect of differential molecular diffusion in DNS of turbulent non-premixed flames

DOE PAGES

Han, Chao; Lignell, David O.; Hawkes, Evatt R.; ...

2017-02-09

Here, the effect of differential molecular diffusion (DMD) in turbulent non-premixed flames is studied by examining two previously reported DNS of temporally evolving planar jet flames, one with CO/H 2 as the fuel and the other with C 2H 4 as the fuel. The effect of DMD in the CO/H 2 DNS flames in which H 2 is part of fuel is found to behave similar to laminar flamelet, while in the C 2H 4 DNS flames in which H 2 is not present in the fuel it is similar to laminar flamelet in early stages but becomes different frommore » laminar flamelet later. The scaling of the effect of DMD with respect to the Reynolds number Re is investigated in the CO/H 2 DNS flames, and an evident power law scaling (~Re –a with a a positive constant) is observed. The scaling of the effect of DMD with respect to the Damkohler number Da is explored in both laminar counter-flow jet C 2H 4 diffusion flames and the C 2H 4 DNS flames. A power law scaling (~ Daa with a a positive constant) is clearly demonstrated for C 2H 4 nonpremixed flames.« less

Ambient ultrafine particles activate human monocytes: Effect of dose, differentiation state and age of donors.

PubMed

Bliss, Bishop; Tran, Kevin Ivan; Sioutas, Constantinos; Campbell, Arezoo

2018-02-01

Exposure to ambient particulate matter (PM) has been linked to adverse pulmonary and cardiovascular health effects. Activation of both inflammatory and oxidative stress pathways has been observed and may be a probable cause of these outcomes. We tested the hypothesis that in human monocytes, PM-induced oxidative and inflammatory responses are interrelated. A human monocytic cell line (THP-1) was used to determine if dose and differentiation state plays a role in the cellular response after a 24hr exposure to particles. Primary human monocytes derived from eight female, non-smoker donors (aged: 21, 24, 27, 28, 48, 49, 54 & 60yo) were used to determine if the age of donors modulates the response. Cells were treated with aqueous suspensions of ambient ultrafine particles (UFP, defined as smaller than 0.2µm in size) or a media control for 24hr. After exposure, reactive oxygen species (ROS) formation was increased irrespective of dose or differentiation state of THP-1 cells. In the primary human monocytes, ROS formation was not significantly changed. The release of the proinflammatory cytokine, tumor necrosis factor alpha (TNF-α), was dose-dependent and greatest in differentiated compared to undifferentiated THP-1 cells exposed to UFP. In the Primary human monocytes, TNF-α secretion was increased irrespective of the age of the donor. Our results suggest that after a 24hr exposure to particles, general reactive oxygen species formation was nonspecific and uncorrelated to cytokine secretion which was consistently enhanced. Cytokines play an important role in orchestrating many immune responses and thus the ability of ambient particles to enhance robust secretion of a proinflammatory cytokine from primary human monocytes, and how this may influence the response to pathogens and alter disease states, needs to be further evaluated. Copyright © 2017 Elsevier Inc. All rights reserved.

Propionibacterium acnes induces an adjuvant effect in B-1 cells and affects their phagocyte differentiation via a TLR2-mediated mechanism.

PubMed

Gambero, Monica; Teixeira, Daniela; Butin, Liane; Ishimura, Mayari Eika; Mariano, Mario; Popi, Ana Flavia; Longo-Maugéri, Ieda Maria

2016-09-01

B-1 lymphocytes are present in large numbers in the mouse peritoneal cavity, as are macrophages, and are responsible for natural IgM production. These lymphocytes migrate to inflammatory foci and are also involved in innate immunity. It was also demonstrated that B-1 cells are able to differentiated into phagocytes (B-1CDP), which is characterized by expression of F4/80 and increased phagocytic activity. B-1 cell responses to antigens and adjuvants are poorly characterized. It has been shown that Propionibacterium acnes suspensions induce immunomodulatory effects in both macrophages and B-2 lymphocytes. We recently demonstrated that this bacterium has the ability to increase B-1 cell populations both in vitro and in vivo. P. acnes induces B-1CDP differentiation, increases the expression of TLR2, TLR4 and TLR9 and augments the expression of CD80, CD86 and CD40 in B-1 and B-1CDP cells. Because P. acnes has been shown to modulate TLR expression, in this study, we investigated the role of TLR2 and TLR4 in B-1 cell population, including B-1CDP differentiation and phagocytic activity in vitro and in vivo. Interestingly, we have demonstrated that TLR2 signaling could be involved in the increase in the B-1 cell population induced by P. acnes. Furthermore, the early differentiation of B-1CDP is also dependent of TLR2. It was also observed that TLR signals also interfere in the phagocytic ability of B-1 cells and their phagocytes. According to these data, it is clear that P. acnes promotes an important adjuvant effect in B-1 cells by inducing them to differentiate into B-1CDP cells and modulates their phagocytic functions both in vivo and in vitro. Moreover, most of these effects are mediated primarily via TLR2. These data reinforce the findings that such bacterial suspensions have powerful adjuvant properties. The responses of B-1 cells to exogenous stimulation indicate that these cells are important to the innate immune response. Copyright © 2016 Elsevier GmbH. All rights

[Comprehensive regulation effect of traditional Chinese medicine on proliferation and differentiation of neural stem cells].

PubMed

Wang, Hong-Jin; Li, Jing-Jing; Ke, Hui; Xu, Xiao-Yu

2017-11-01

Since the discovery of neural stem cells(NSCs) in embryonic and adult mammalian central nervous systems, new approaches for proliferation and differentiation of NSCs have been put forward. One of the approaches to promote the clinical application of NSCs is to search effective methods to regulate the proliferation and differentiation. This problem is urgently to be solved in the medical field. Previous studies have shown that traditional Chinese medicine could promote the proliferation and differentiation of NSCs by regulating the relevant signaling pathway in vivo and in vitro. Domestic and foreign literatures for regulating the proliferation and differentiation of neural stem cells in recent 10 years and the reports for their target and signaling pathways were analyzed in this paper. Traditional Chinese medicine could regulate the proliferation and differentiation of NSCs through signaling pathways of Notch, PI3K/Akt, Wnt/β-catenin and GFs. However, studies about NSCs and traditional Chinese medicine should be further deepened; the mechanism of multiple targets and the comprehensive regulation function of traditional Chinese medicine should be clarified. Copyright© by the Chinese Pharmaceutical Association.

Gender-Based Wage Differentials in a Predominantly Female Profession: Observations from Nursing

ERIC Educational Resources Information Center

Jones, Cheryl, Bland; Gates, Michael

2004-01-01

Despite numerous studies examining nursing wages, very little attention has focused on nursing wage differentials. We build on previous research by modeling nursing wages and examining male-female wage differences within the context of the current nursing shortage. Our results show that male nurses do earn a wage premium, largely explained by…

Impedance Discontinuity Reduction Between High-Speed Differential Connectors and PCB Interfaces

NASA Technical Reports Server (NTRS)

Navidi, Sal; Agdinaoay, Rodell; Walter, Keith

2013-01-01

High-speed serial communication (i.e., Gigabit Ethernet) requires differential transmission and controlled impedances. Impedance control is essential throughout cabling, connector, and circuit board construction. An impedance discontinuity arises at the interface of a high-speed quadrax and twinax connectors and the attached printed circuit board (PCB). This discontinuity usually is lower impedance since the relative dielectric constant of the board is higher (i.e., polyimide approx. = 4) than the connector (Teflon approx. = 2.25). The discontinuity can be observed in transmit or receive eye diagrams, and can reduce the effective link margin of serial data networks. High-speed serial data network transmission improvements can be made at the connector-to-board interfaces as well as improving differential via hole impedances. The impedance discontinuity was improved by 10 percent by drilling a 20-mil (approx. = 0.5-mm) hole in between the pin of a differential connector spaced 55 mils (approx. = 1.4 mm) apart as it is attached to the PCB. The effective dielectric constant of the board can be lowered by drilling holes into the board material between the differential lines in a quadrax or twinax connector attachment points. The differential impedance is inversely proportional to the square root of the relative dielectric constant. This increases the differential impedance and thus reduces the above described impedance discontinuity. The differential via hole impedance can also be increased in the same manner. This technique can be extended to multiple smaller drilled holes as well as tapered holes (i.e., big in the middle followed by smaller ones diagonally).

The Effect of Amplifier Bias Drift on Differential Magnitude Estimation in Multiple-Star Systems

NASA Astrophysics Data System (ADS)

Tyler, David W.; Muralimanohar, Hariharan; Borelli, Kathy J.

2007-02-01

We show how the temporal drift of CCD amplifier bias can cause significant relative magnitude estimation error in speckle interferometric observations of multiple-star systems. When amplifier bias varies over time, the estimation error arises if the time between acquisition of dark-frame calibration data and science data is long relative to the timescale over which the bias changes. Using analysis, we show that while detector-temperature drift over time causes a variation in accumulated dark current and a residual bias in calibrated imagery, only amplifier bias variations cause a residual bias in the estimated energy spectrum. We then use telescope data taken specifically to investigate this phenomenon to show that for the detector used, temporal bias drift can cause residual energy spectrum bias as large or larger than the mean value of the noise energy spectrum. Finally, we use a computer simulation to demonstrate the effect of residual bias on differential magnitude estimation. A supplemental calibration technique is described in the appendices.

Macrophage differentiation induced by PMA is mediated by activation of RhoA/ROCK signaling.

PubMed

Yang, Lifeng; Dai, Fan; Tang, Lian; Le, Yulan; Yao, Wenjuan

2017-01-01

In order to investigate the effects of RhoA/ROCK signaling in macrophage differentiation, we used 100 ng/mL PMA to induce macrophage differentiation from U937 cells in vitro. The observation of cell morphology and the expression of CD68 and SR-A were performed to confirm the differentiation induced by PMA. Western blot analysis showed that the expression of ROCK1 and ROCK2 and the phosphorylation of MYPT1 were significantly increased after PMA treatment. Pulldown assay showed that the activation of RhoA was obviously enhanced when U937 cells were treated with PMA. In order to further demonstrate whether RhoA/ROCK signaling could mediate the macrophage differentiation induced by PMA, we successfully suppressed the expression of RhoA, ROCK1 and ROCK2 by performing siRNA technology in U937 cells, respectively. The macrophage differentiation and the expression of CD68 and SR-A were significantly inhibited by the suppression of RhoA, ROCK1 or ROCK2 in PMA-induced U937 cells, indicating that the macrophage differentiation induced by PMA is associated with RhoA/ROCK signaling pathway. In addition, we pretreated U937 cells with Y27632 (ROCK inhibitor, 20 μM) for 30 min and then observed the macrophage differentiation induced by PMA. The result illustrated that Y27632 pretreatment obviously inhibited PMA-induced differentiation and the expression of CD68 and SR-A. In conclusion, the activation of RhoA/ROCK signaling is responsible for the macrophage differentiation induced by PMA.

Effects of ionizing radiation on bone cell differentiation in an experimental murine bone cell model

NASA Astrophysics Data System (ADS)

Baumstark-Khan, Christa; Lau, Patrick; Hellweg, Christine; Reitz, Guenther

-immunostaining. Osteoblastogenesis was estimated by measurement of alkaline phosphatase (ALP) activity and production of mineralized matrix (von-Kossa staining, Alizarin Red staining). During the process of osteoblastic cell differentiation, the expression of the bone specific marker genes osteocalcin (OCN) and osteopontin (OPN) were recorded by quantitative real time reverse transcription PCR (qRT-PCR). Compared with standard culture conditions, the osteogenic marker genes OCN and OPN were highly expressed during the differentiation process induced either by osteo-inductive media additives (50 µg/ml ascorbic acid, 10 mmol/l β-glycero phosphate) or by sparsely ionizing radiation (X-rays). After 21 days of postirradiation incubation sparsely ionizing radiation could be shown to induce the formation of bone-like nodules (von-Kossa staining) for OCT-1 and MC3T3-E1 S4 cells but nor for MC3T3- E1 S24 cells. Ionizing radiation leads to a cell cycle arrest which is resolved in a dose and time dependent way. This was accompanied by a dose dependent regulation of the cyclin kinase inhibitor CDKN1A (p21/WAF) and transforming growth factor beta 1 (TGF-β1). TGF-β1 is known to affect osteoblast differentiation, matrix formation and mineralization. Modulation of its expression could influence the expression of main osteogenic transcription factors. For exposure with high LET radiation a pronounced cell cycle block was evident. The expression of the osteogenic marker genes OCN and Osterix (OSX) was increased in the OCT-1 cells with differentiation potential for exposure to α particles and accelerated carbon and argon ions. The results on the expression of differentiation markers during radiation-induced premature differentiation of bone cells of the osteoblast lineage show that densely ionizing radiation results in expression of proteins essential for bone formation and consequently in an increase in bone volume. Such an effect has been observed in in-vivo carbon ion irradiated rats. As radiation dependent

DYNAMO EFFECTS NEAR THE TRANSITION FROM SOLAR TO ANTI-SOLAR DIFFERENTIAL ROTATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simitev, Radostin D.; Kosovichev, Alexander G.; Busse, Friedrich H.

2015-09-01

Numerical MHD simulations play an increasingly important role for understanding the mechanisms of stellar magnetism. We present simulations of convection and dynamos in density-stratified rotating spherical fluid shells. We employ a new 3D simulation code for obtaining the solution of a physically consistent anelastic model of the process with a minimum number of parameters. The reported dynamo simulations extend into a “buoyancy-dominated” regime where the buoyancy forcing is dominant while the Coriolis force is no longer balanced by pressure gradients, and strong anti-solar differential rotation develops as a result. We find that the self-generated magnetic fields, despite being relatively weak,more » are able to reverse the direction of differential rotation from anti-solar to solar-like. We also find that convection flows in this regime are significantly stronger in the polar regions than in the equatorial region, leading to non-oscillatory dipole-dominated dynamo solutions, and to a concentration of magnetic field in the polar regions. We observe that convection has a different morphology in the inner and the outer part of the convection zone simultaneously such that organized geostrophic convection columns are hidden below a near-surface layer of well-mixed highly chaotic convection. While we focus our attention on the buoyancy-dominated regime, we also demonstrate that conical differential rotation profiles and persistent regular dynamo oscillations can be obtained in the parameter space of the rotation-dominated regime even within this minimal model.« less

Differential effects of phthalates on the testis and the liver.

PubMed

Bhattacharya, Nandini; Dufour, Jannette M; Vo, My-Nuong; Okita, Janice; Okita, Richard; Kim, Kwan Hee

2005-03-01

Phthalates have been shown to elicit contrasting effects on the testis and the liver, causing testicular degeneration and promoting abnormal hepatocyte proliferation and carcinogenesis. In the present study, we compared the effects of phthalates on testicular and liver cells to better understand the mechanisms by which phthalates cause testicular degeneration. In vivo treatment of rats with di-(2-ethylhexyl) phthalate (DEHP) caused a threefold increase of germ cell apoptosis in the testis, whereas apoptosis was not changed significantly in livers from the same animals. Western blot analyses revealed that peroxisome proliferator-activated receptor (PPAR) alpha is equally abundant in the liver and the testis, whereas PPAR gamma and retinoic acid receptor (RAR) alpha are expressed more in the testis. To determine whether the principal metabolite of DEHP, mono-(2-ethylhexyl) phthalate (MEHP), or a strong peroxisome proliferator, 4-chloro-6(2,3-xylindino)-2-pyrimidinylthioacetic acid (Wy-14,643), have a differential effect in Sertoli and liver cells by altering the function of RAR alpha and PPARs, their nuclear trafficking patterns were compared in Sertoli and liver cells after treatment. Both MEHP and Wy-14,643 increased the nuclear localization of PPAR alpha and PPAR gamma in Sertoli cells, but they decreased the nuclear localization of RAR alpha, as previously shown. Both PPAR alpha and PPAR gamma were in the nucleus and cytoplasm of liver cells, but RAR alpha was predominant in the cytoplasm, regardless of the treatment. At the molecular level, MEHP and Wy-14,643 reduced the amount of phosphorylated mitogen-activated protein kinase (activated MAPK) in Sertoli cells. In comparison, both MEHP and Wy-14,643 increased phosphorylated MAPK in liver cells. These results suggest that phthalates may cause contrasting effects on the testis and the liver by differential activation of the MAPK pathway, RAR alpha, PPAR alpha, and PPAR gamma in these organs.

Age-Differential Effects of Job Characteristics on Job Attraction: A Policy-Capturing Study

PubMed Central

Zacher, Hannes; Dirkers, Bodil T.; Korek, Sabine; Hughes, Brenda

2017-01-01

Based on an integration of job design and lifespan developmental theories, Truxillo et al. (2012) proposed that job characteristics interact with employee age in predicting important work outcomes. Using an experimental policy-capturing design, we investigated age-differential effects of four core job characteristics (i.e., job autonomy, task variety, task significance, and feedback from the job) on job attraction (i.e., individuals' rating of job attractiveness). Eighty-two employees between 19 and 65 years (Mage = 41, SD = 14) indicated their job attraction for each of 40 hypothetical job descriptions in which the four job characteristics were systematically manipulated (in total, participants provided 3,280 ratings). Results of multilevel analyses showed that the positive effects of task variety, task significance, and feedback from the job were stronger for younger compared to older employees, whereas we did not find significant age-differential effects of job autonomy on job attraction. These findings are only partially consistent with propositions of Truxillo et al.'s (2012) lifespan perspective on job design. PMID:28713322

Age-Differential Effects of Job Characteristics on Job Attraction: A Policy-Capturing Study.

PubMed

Zacher, Hannes; Dirkers, Bodil T; Korek, Sabine; Hughes, Brenda

2017-01-01

Based on an integration of job design and lifespan developmental theories, Truxillo et al. (2012) proposed that job characteristics interact with employee age in predicting important work outcomes. Using an experimental policy-capturing design, we investigated age-differential effects of four core job characteristics (i.e., job autonomy, task variety, task significance, and feedback from the job) on job attraction (i.e., individuals' rating of job attractiveness). Eighty-two employees between 19 and 65 years ( M age = 41, SD = 14) indicated their job attraction for each of 40 hypothetical job descriptions in which the four job characteristics were systematically manipulated (in total, participants provided 3,280 ratings). Results of multilevel analyses showed that the positive effects of task variety, task significance, and feedback from the job were stronger for younger compared to older employees, whereas we did not find significant age-differential effects of job autonomy on job attraction. These findings are only partially consistent with propositions of Truxillo et al.'s (2012) lifespan perspective on job design.

Differentiating Science Instruction: Secondary science teachers' practices

NASA Astrophysics Data System (ADS)

Maeng, Jennifer L.; Bell, Randy L.

2015-09-01

This descriptive study investigated the implementation practices of secondary science teachers who differentiate instruction. Participants included seven high school science teachers purposefully selected from four different schools located in a mid-Atlantic state. Purposeful selection ensured participants included differentiated instruction (DI) in their lesson implementation. Data included semi-structured interviews and field notes from a minimum of four classroom observations, selected to capture the variety of differentiation strategies employed. These data were analyzed using a constant-comparative approach. Each classroom observation was scored using the validated Differentiated Instruction Implementation Matrix-Modified, which captured both the extent to which critical indicators of DI were present in teachers' instruction and the performance levels at which they engaged in these components of DI. Results indicated participants implemented a variety of differentiation strategies in their classrooms with varying proficiency. Evidence suggested all participants used instructional modifications that required little advance preparation to accommodate differences in students' interests and learning profile. Four of the seven participants implemented more complex instructional strategies that required substantial advance preparation by the teacher. Most significantly, this study provides practical strategies for in-service science teachers beginning to differentiate instruction and recommendations for professional development and preservice science teacher education.

Thin Film Differential Photosensor for Reduction of Temperature Effects in Lab-on-Chip Applications

PubMed Central

de Cesare, Giampiero; Carpentiero, Matteo; Nascetti, Augusto; Caputo, Domenico

2016-01-01

This paper presents a thin film structure suitable for low-level radiation measurements in lab-on-chip systems that are subject to thermal treatments of the analyte and/or to large temperature variations. The device is the series connection of two amorphous silicon/amorphous silicon carbide heterojunctions designed to perform differential current measurements. The two diodes experience the same temperature, while only one is exposed to the incident radiation. Under these conditions, temperature and light are the common and differential mode signals, respectively. A proper electrical connection reads the differential current of the two diodes (ideally the photocurrent) as the output signal. The experimental characterization shows the benefits of the differential structure in minimizing the temperature effects with respect to a single diode operation. In particular, when the temperature varies from 23 to 50 °C, the proposed device shows a common mode rejection ratio up to 24 dB and reduces of a factor of three the error in detecting very low-intensity light signals. PMID:26907292

Zinc Promotes Adipose-Derived Mesenchymal Stem Cell Proliferation and Differentiation towards a Neuronal Fate.

PubMed

Moon, Mi-Young; Kim, Hyun Jung; Choi, Bo Young; Sohn, Min; Chung, Tae Nyoung; Suh, Sang Won

2018-01-01

Zinc is an essential element required for cell division, migration, and proliferation. Under zinc-deficient conditions, proliferation and differentiation of neural progenitors are significantly impaired. Adipose-derived mesenchymal stem cells (AD-MSCs) are multipotent stem cells that can differentiate into neurons. The aim of this study was to evaluate the effect of zinc on AD-MSC proliferation and differentiation. We initially examined the effect of zinc on stem cell proliferation at the undifferentiated stage. AD-MSCs showed high proliferation rates on day 6 in 30  μ M and 100  μ M of ZnCl 2 . Zinc chelation inhibited AD-MSC proliferation via downregulation of ERK1/2 activity. We then assessed whether zinc was involved in cell migration and neurite outgrowth during differentiation. After three days of neuronal differentiation, TUJ-1-positive cells were observed, implying that AD-MSCs had differentiated into early neuron or neuron-like cells. Neurite outgrowth was increased in the zinc-treated group, while the CaEDTA-treated group showed diminished, shrunken neurites. Furthermore, we showed that zinc promoted neurite outgrowth via the inactivation of RhoA and led to the induction of neuronal gene expression (MAP2 and nestin) in differentiated stem cells. Taken together, zinc promoted AD-MSC proliferation and affected neuronal differentiation, mainly by increasing neurite outgrowth.

Zinc Promotes Adipose-Derived Mesenchymal Stem Cell Proliferation and Differentiation towards a Neuronal Fate

PubMed Central

Moon, Mi-Young; Kim, Hyun Jung; Choi, Bo Young; Sohn, Min

2018-01-01

Zinc is an essential element required for cell division, migration, and proliferation. Under zinc-deficient conditions, proliferation and differentiation of neural progenitors are significantly impaired. Adipose-derived mesenchymal stem cells (AD-MSCs) are multipotent stem cells that can differentiate into neurons. The aim of this study was to evaluate the effect of zinc on AD-MSC proliferation and differentiation. We initially examined the effect of zinc on stem cell proliferation at the undifferentiated stage. AD-MSCs showed high proliferation rates on day 6 in 30 μM and 100 μM of ZnCl2. Zinc chelation inhibited AD-MSC proliferation via downregulation of ERK1/2 activity. We then assessed whether zinc was involved in cell migration and neurite outgrowth during differentiation. After three days of neuronal differentiation, TUJ-1-positive cells were observed, implying that AD-MSCs had differentiated into early neuron or neuron-like cells. Neurite outgrowth was increased in the zinc-treated group, while the CaEDTA-treated group showed diminished, shrunken neurites. Furthermore, we showed that zinc promoted neurite outgrowth via the inactivation of RhoA and led to the induction of neuronal gene expression (MAP2 and nestin) in differentiated stem cells. Taken together, zinc promoted AD-MSC proliferation and affected neuronal differentiation, mainly by increasing neurite outgrowth. PMID:29765417

Effects and mechanisms of melatonin on neural differentiation of induced pluripotent stem cells.

PubMed

Shu, Tao; Wu, Tao; Pang, Mao; Liu, Chang; Wang, Xuan; Wang, Juan; Liu, Bin; Rong, Limin

2016-06-03

Melatonin, a lipophilic molecule mainly synthesized in the pineal gland, has properties of antioxidation, anti-inflammation, and antiapoptosis to improve neuroprotective functions. Here, we investigate effects and mechanisms of melatonin on neural differentiation of induced pluripotent stem cells (iPSCs). iPSCs were induced into neural stem cells (NSCs), then further differentiated into neurons in medium with or without melatonin, melatonin receptor antagonist (Luzindole) or Phosphatidylinositide 3 kinase (PI3K) inhibitor (LY294002). Melatonin significantly promoted the number of neurospheres and cell viability. In addition, Melatonin markedly up-regulated gene and protein expression of Nestin and MAP2. However, Luzindole or LY294002 attenuated these increase. The expression of pAKT/AKT were increased by Melatonin, while Luzindole or LY294002 declined these melatonin-induced increase. These results suggest that melatonin significantly increased neural differentiation of iPSCs via activating PI3K/AKT signaling pathway through melatonin receptor. Copyright © 2016 Elsevier Inc. All rights reserved.

The effects of dexamethasone, ascorbic acid, and β-glycerophosphate on osteoblastic differentiation by regulating estrogen receptor and osteopontin expression.

PubMed

Park, Jun-Beom

2012-03-01

Ascorbic acid (AA), β-glycerophosphate (GP), and dexamethasone (DEX) are the compounds known to favor the expression of the osteoblastic phenotype in several bone cell systems. In this report, the combination effects of differentiation agents on osteoprecursor cells were evaluated. The effect on cell proliferation was determined by a cell viability test with morphologic analysis. Differentiation and mineralization were evaluated using an alkaline phosphatase activity test and alizarin red-S staining. Protein expressions related to bone formation, such as transforming growth factor-beta (TGF-β), estrogen receptor-alpha (ER-α), and osteopontin (OPN) were evaluated by using a Western blot analysis. AA and GP provided an inductive effect for differentiation of osteoprecusor cells, while short-term application of DEX seemed to lead to a dose-dependent increase of cellular differentiation. Long-term use of DEX seemed to reduce mineralization. These effects may seem to be regulated by the expression of ER-α, OPN, and TGF-β. Further studies related to this mechanism within the in vivo model may be necessary to ascertain greater detail. Copyright © 2012 Elsevier Inc. All rights reserved.

Metabolic reprogramming during neuronal differentiation.

PubMed

Agostini, M; Romeo, F; Inoue, S; Niklison-Chirou, M V; Elia, A J; Dinsdale, D; Morone, N; Knight, R A; Mak, T W; Melino, G

2016-09-01

Newly generated neurons pass through a series of well-defined developmental stages, which allow them to integrate into existing neuronal circuits. After exit from the cell cycle, postmitotic neurons undergo neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. Lack of a global metabolic analysis during early cortical neuronal development led us to explore the role of cellular metabolism and mitochondrial biology during ex vivo differentiation of primary cortical neurons. Unexpectedly, we observed a huge increase in mitochondrial biogenesis. Changes in mitochondrial mass, morphology and function were correlated with the upregulation of the master regulators of mitochondrial biogenesis, TFAM and PGC-1α. Concomitant with mitochondrial biogenesis, we observed an increase in glucose metabolism during neuronal differentiation, which was linked to an increase in glucose uptake and enhanced GLUT3 mRNA expression and platelet isoform of phosphofructokinase 1 (PFKp) protein expression. In addition, glutamate-glutamine metabolism was also increased during the differentiation of cortical neurons. We identified PI3K-Akt-mTOR signalling as a critical regulator role of energy metabolism in neurons. Selective pharmacological inhibition of these metabolic pathways indicate existence of metabolic checkpoint that need to be satisfied in order to allow neuronal differentiation.

Metabolic reprogramming during neuronal differentiation

PubMed Central

Agostini, M; Romeo, F; Inoue, S; Niklison-Chirou, M V; Elia, A J; Dinsdale, D; Morone, N; Knight, R A; Mak, T W; Melino, G

2016-01-01

Newly generated neurons pass through a series of well-defined developmental stages, which allow them to integrate into existing neuronal circuits. After exit from the cell cycle, postmitotic neurons undergo neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. Lack of a global metabolic analysis during early cortical neuronal development led us to explore the role of cellular metabolism and mitochondrial biology during ex vivo differentiation of primary cortical neurons. Unexpectedly, we observed a huge increase in mitochondrial biogenesis. Changes in mitochondrial mass, morphology and function were correlated with the upregulation of the master regulators of mitochondrial biogenesis, TFAM and PGC-1α. Concomitant with mitochondrial biogenesis, we observed an increase in glucose metabolism during neuronal differentiation, which was linked to an increase in glucose uptake and enhanced GLUT3 mRNA expression and platelet isoform of phosphofructokinase 1 (PFKp) protein expression. In addition, glutamate–glutamine metabolism was also increased during the differentiation of cortical neurons. We identified PI3K–Akt–mTOR signalling as a critical regulator role of energy metabolism in neurons. Selective pharmacological inhibition of these metabolic pathways indicate existence of metabolic checkpoint that need to be satisfied in order to allow neuronal differentiation. PMID:27058317

The role of parental personality traits in differential parenting.

PubMed

Browne, Dillon T; Meunier, Jean Christophe; O'Connor, Thomas G; Jenkins, Jennifer M

2012-08-01

Significant relationships have been demonstrated between parental personality and parenting toward individual children, but there is little research exploring the relationship between parental personality and differential parenting (DP). The present study examined the relationship between the Big Five personality dimensions and differential positivity and negativity in parenting (observed and self-report measures). The analyses are based on a sample of 867 children nested within 381 families. Using multilevel modeling and controlling for child age, gender, birth order, behavior, and family socioeconomic status analyses revealed that maternal and paternal agreeableness were inversely related to reports of differential positivity. Agreeableness predicted observed differential negativity, and the relationship was curvilinear (at both high and low levels of agreeableness, differential negativity was higher). Finally, mothers with the most openness to experience exhibited the highest levels of reported differential negativity. The findings suggest that parental personality is a modest yet important influence to consider when conceptualizing the sources of DP. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Effect of acetaminophen on osteoblastic differentiation and migration of MC3T3-E1 cells.

PubMed

Nakatsu, Yoshihiro; Nakagawa, Fumio; Higashi, Sen; Ohsumi, Tomoko; Shiiba, Shunji; Watanabe, Seiji; Takeuchi, Hiroshi

2018-02-01

N-acetyl-p-aminophenol (APAP, acetaminophen, paracetamol) is a widely used analgesic/antipyretic with weak inhibitory effects on cyclooxygenase (COX) compared to non-steroidal anti-inflammatory drugs (NSAIDs). The mechanism of action of APAP is mediated by its metabolite that activates transient receptor potential channels, including transient receptor potential vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) or the cannabinoid receptor type 1 (CB1). However, the exact molecular mechanism and target underlying the cellular actions of APAP remain unclear. Therefore, we investigated the effect of APAP on osteoblastic differentiation and cell migration, with a particular focus on TRP channels and CB1. Effects of APAP on osteoblastic differentiation and cell migration of MC3T3-E1, a mouse pre-osteoblast cell line, were assessed by the increase in alkaline phosphatase (ALP) activity, and both wound-healing and transwell-migration assays, respectively. APAP dose-dependently inhibited osteoblastic differentiation, which was well correlated with the effects on COX activity compared with other NSAIDs. In contrast, cell migration was promoted by APAP, and this effect was not correlated with COX inhibition. None of the agonists or antagonists of TRP channels and the CB receptor affected the APAP-induced cell migration, while the effect of APAP on cell migration was abolished by down-regulating TRPV4 gene expression. APAP inhibited osteoblastic differentiation via COX inactivation while it promoted cell migration independently of previously known targets such as COX, TRPV1, TRPA1 channels, and CB receptors, but through the mechanism involving TRPV4. APAP may have still unidentified molecular targets that modify cellular functions. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

In vitro effect of mineralized and demineralized bone allografts on proliferation and differentiation of MG-63 osteoblast-like cells.

PubMed

Lafzi, Ardeshir; Vahabi, Surena; Ghods, Shadab; Torshabi, Maryam

2016-03-01

Due to the extensive use of bone allografts in bone reconstruction and periodontal therapy as suitable alternatives to autografts, they are now marketed under different commercial brands. Considering the controversial reports regarding the osteoinductive properties of bone allografts, this study sought to assess the effect of type (mineralized/demineralized), amount and particle size of several allografts on the proliferation and differentiation of MG-63 osteoblast-like cells. MG-63 cells (24-h culture) were exposed to 20 and 40 mg amounts of nine different commercially available freeze-dried bone allografts. After 24 and 72 h of incubation, the effect of water-soluble allograft released materials on cell viability and proliferation was assessed using methyl thiazol tetrazolium (MTT) assay after 24 and 72 h of exposure. Cell differentiation and mineralization was assessed by real-time quantitative reverse transcription PCR and alizarin red staining after 72 h of exposure. The amount and particle size of understudy allografts had significant effects on cell viability after 24 h of exposure (in contrast to 72 h). Higher rate of proliferation was seen in non-differentiated or slow-differentiated groups. The amount and particle size factors had no significant effect on the amount of calcified nodules or the expression of osteogenic marker genes in most groups. Faster and more distinct differentiation and mineralization was noted in mineralized compared to demineralized groups during the 3-day study period. Based on the results, the understudy mineralized (non-demineralized) bone allografts had greater effect on osteogenic differentiation of the MG-63 cells and showed more in vitro osteoinductive activity compared to partially demineralized and fully demineralized types.

Differential susceptibility to discipline: the moderating effect of child temperament on the association between maternal discipline and early childhood externalizing problems.

PubMed

van Zeijl, Jantien; Mesman, Judi; Stolk, Mirjam N; Alink, Lenneke R A; van Ijzendoorn, Marinus H; Bakermans-Kranenburg, Marian J; Juffer, Femmie; Koot, Hans M

2007-12-01

This study investigated the interaction of child temperament and maternal discipline in the prediction of externalizing problems in early childhood. Interaction effects were evaluated in a sample of 227 one- to three-year-old children with relatively high externalizing problems scores on the Child Behavior Checklist/1 1/2-5. Child temperament was reported by the mothers, maternal discipline was observed in a laboratory session, and child outcome measures included both mother-reported externalizing problems and observed physical aggression. Results indicate that children with difficult temperaments are more susceptible to negative discipline (i.e., they showed more externalizing problems) as well as more susceptible to positive discipline (i.e., they showed fewer externalizing problems and less physical aggression), as compared with children with relatively easy temperaments. These findings provide empirical evidence for the differential susceptibility hypothesis and suggest directions for enhancing the effectiveness of interventions aimed at reducing early childhood externalizing problems.

Early differential processing of material images: Evidence from ERP classification.

PubMed

Wiebel, Christiane B; Valsecchi, Matteo; Gegenfurtner, Karl R

2014-06-24

Investigating the temporal dynamics of natural image processing using event-related potentials (ERPs) has a long tradition in object recognition research. In a classical Go-NoGo task two characteristic effects have been emphasized: an early task independent category effect and a later task-dependent target effect. Here, we set out to use this well-established Go-NoGo paradigm to study the time course of material categorization. Material perception has gained more and more interest over the years as its importance in natural viewing conditions has been ignored for a long time. In addition to analyzing standard ERPs, we conducted a single trial ERP pattern analysis. To validate this procedure, we also measured ERPs in two object categories (people and animals). Our linear classification procedure was able to largely capture the overall pattern of results from the canonical analysis of the ERPs and even extend it. We replicate the known target effect (differential Go-NoGo potential at frontal sites) for the material images. Furthermore, we observe task-independent differential activity between the two material categories as early as 140 ms after stimulus onset. Using our linear classification approach, we show that material categories can be differentiated consistently based on the ERP pattern in single trials around 100 ms after stimulus onset, independent of the target-related status. This strengthens the idea of early differential visual processing of material categories independent of the task, probably due to differences in low-level image properties and suggests pattern classification of ERP topographies as a strong instrument for investigating electrophysiological brain activity. © 2014 ARVO.

Effect of Uniaxial Tensile Cyclic Loading Regimes on Matrix Organization and Tenogenic Differentiation of Adipose-Derived Stem Cells Encapsulated within 3D Collagen Scaffolds

PubMed Central

Stasuk, Alexander

2017-01-01

Adipose-derived mesenchymal stem cells have become a popular cell choice for tendon repair strategies due to their relative abundance, ease of isolation, and ability to differentiate into tenocytes. In this study, we investigated the solo effect of different uniaxial tensile strains and loading frequencies on the matrix directionality and tenogenic differentiation of adipose-derived stem cells encapsulated within three-dimensional collagen scaffolds. Samples loaded at 0%, 2%, 4%, and 6% strains and 0.1 Hz and 1 Hz frequencies for 2 hours/day over a 7-day period using a custom-built uniaxial tensile strain bioreactor were characterized in terms of matrix organization, cell viability, and musculoskeletal gene expression profiles. The results displayed that the collagen fibers of the loaded samples exhibited increased matrix directionality with an increase in strain values. Gene expression analyses demonstrated that ASC-encapsulated collagen scaffolds loaded at 2% strain and 0.1 Hz frequency showed significant increases in extracellular matrix genes and tenogenic differentiation markers. Importantly, no cross-differentiation potential to osteogenic, chondrogenic, and myogenic lineages was observed at 2% strain and 0.1 Hz frequency loading condition. Thus, 2% strain and 0.1 Hz frequency were identified as the appropriate mechanical loading regime to induce tenogenic differentiation of adipose-derived stem cells cultured in a three-dimensional environment. PMID:29375625

Concurrent Schedules of Positive and Negative Reinforcement: Differential-Impact and Differential-Outcomes Hypotheses

PubMed Central

Magoon, Michael A; Critchfield, Thomas S

2008-01-01

Considerable evidence from outside of operant psychology suggests that aversive events exert greater influence over behavior than equal-sized positive-reinforcement events. Operant theory is largely moot on this point, and most operant research is uninformative because of a scaling problem that prevents aversive events and those based on positive reinforcement from being directly compared. In the present investigation, humans' mouse-click responses were maintained on similarly structured, concurrent schedules of positive (money gain) and negative (avoidance of money loss) reinforcement. Because gains and losses were of equal magnitude, according to the analytical conventions of the generalized matching law, bias (log b ≠ 0) would indicate differential impact by one type of consequence; however, no systematic bias was observed. Further research is needed to reconcile this outcome with apparently robust findings in other literatures of superior behavior control by aversive events. In an incidental finding, the linear function relating log behavior ratio and log reinforcement ratio was steeper for concurrent negative and positive reinforcement than for control conditions involving concurrent positive reinforcement. This may represent the first empirical confirmation of a free-operant differential-outcomes effect predicted by contingency-discriminability theories of choice. PMID:18683609

Effects of differential habitat warming on complex communities.

PubMed

Tunney, Tyler D; McCann, Kevin S; Lester, Nigel P; Shuter, Brian J

2014-06-03

Food webs unfold across a mosaic of micro and macro habitats, with each habitat coupled by mobile consumers that behave in response to local environmental conditions. Despite this fundamental characteristic of nature, research on how climate change will affect whole ecosystems has overlooked (i) that climate warming will generally affect habitats differently and (ii) that mobile consumers may respond to this differential change in a manner that may fundamentally alter the energy pathways that sustain ecosystems. This reasoning suggests a powerful, but largely unexplored, avenue for studying the impacts of climate change on ecosystem functioning. Here, we use lake ecosystems to show that predictable behavioral adjustments to local temperature differentials govern a fundamental structural shift across 54 food webs. Data show that the trophic pathways from basal resources to a cold-adapted predator shift toward greater reliance on a cold-water refuge habitat, and food chain length increases, as air temperatures rise. Notably, cold-adapted predator behavior may substantially drive this decoupling effect across the climatic range in our study independent of warmer-adapted species responses (for example, changes in near-shore species abundance and predator absence). Such modifications reflect a flexible food web architecture that requires more attention from climate change research. The trophic pathway restructuring documented here is expected to alter biomass accumulation, through the regulation of energy fluxes to predators, and thus potentially threatens ecosystem sustainability in times of rapid environmental change.

Anti-psoriatic effects of indigo naturalis on the proliferation and differentiation of keratinocytes with indirubin as the active component.

PubMed

Lin, Yin-Ku; Leu, Yann-Lii; Yang, Sien-Hung; Chen, Hsiao-Wen; Wang, Chin-Ting; Pang, Jong-Hwei Su

2009-06-01

Indigo naturalis has shown efficacy in treating psoriasis in our previous clinical studies. To investigate the potential effect of indigo naturalis on regulating keratinocyte proliferation and differentiation. Skin samples from six patients were analyzed for proliferating cell nuclear antigen (PCNA) and involucrin expression by immunohistochemical staining. In addition, indigo naturalis extracts from 10 to 500 microg/ml were added to cultured keratinocytes and cell viability determined. Real-time RT-PCR, Western blotting analysis and indirect immunofluorescent labeling were used to investigate the messenger (m)RNA and protein expressions of PCNA and involucrin. Finally, high-performance liquid chromatography (HPLC) was used to identify major components of indigo naturalis and their in vitro effects compared. Immunohistochemical results demonstrated decreased PCNA and increased involucrin in psoriatic lesions after indigo naturalis treatment. Cultured keratinocytes decreased after indigo naturalis treatment, while G(0)/G(1) arrest was observed to dose-dependently increase. Staining revealed decreased PCNA-stained nuclei and increased cytosolic involucrin in treated keratinocytes. Decreased PCNA and increased involucrin at both the mRNA and protein levels were confirmed. Both major components, indirubin and indigo, could cause G(0)/G(1) phase arrest; however, only indirubin modulated the expressions of PCNA and involucrin similar to indigo naturalis. Together, these findings indicate that the anti-psoriatic effects of indigo naturalis are mediated, at least in part, by modulating the proliferation and differentiation of keratinocytes, with indirubin as the major active component.

A NOVEL EFFECT OF DIOXIN: EXPOSURE DURING PREGNANCY SEVERELY IMPAIRS MAMMARY GLAND DIFFERENTIATION

EPA Science Inventory

A novel effect of dioxin: Exposure during pregnancy severely impairs mammary gland differentiation.
Beth A. Vorderstrasse1, Suzanne E. Fenton2, Andrea A. Bohn3, Jennifer A. Cundiff1, and B. Paige Lawrence1,3,4 1Department of Pharmaceutical Sciences, Washington State Universi...

Characterization of A Three-Dimensional Organotypic Co-Culture Skin Model for Epidermal Differentiation of Rat Adipose-Derived Stem Cells.

PubMed

Ghanavati, Zeinab; Orazizadeh, Mahmoud; Bayati, Vahid; Abbaspour, Mohammad Reza; Khorsandi, Layasadat; Mansouri, Esrafil; Neisi, Niloofar

2016-01-01

The organotypic co-culture is a well-known technique to examine cellular interactions and their roles in stem cell proliferation and differentiation. This study aims to evaluate the effects of dermal fibroblasts (DFs) on epidermal differentiation of adipose-derived stem cells (ASCs) using a three-dimensional (3D) organotypic co- culture technique. In this experimental research study, rat DFs and ASCs were isolated and cultured separately on electrospun polycaprolactone (PCL) matrices. The PCL matrices seeded by ASCs were superimposed on to the matrices seeded by DFs in order to create a 3D organotypic co-culture. In the control groups, PCL matrices seeded by ASCs were placed on matrices devoid of DFs. After 10 days, we assessed the expressions of keratinocyte-related genes by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and expression of pan-cytokeratin protein by immunofluorescence in the differentiated keratinocyte-like cells from co- culture and control groups. Keratinocyte-like cell morphologies were also observed by scanning electron microscopy (SEM). The early, intermediate, and terminal differentiation keratinocyte markers-Cytokeratin14, Filaggrin, and Involucrin significantly expressed in the co-culture groups com- pared to the control ones (P<0.05). We observed pan-cytokeratin in keratinocyte-like cells of both groups by immunofluorescence. SEM observation of the co-culture groups showed that the differentiated keratinocyte-like cells developed a polygonal cobblestone shape, considered characteristic of keratinocytes. The 3D organotypic co-culture bilayered construct that consisted of DFs and ASCs was an effective technique for epidermal differentiation of ASCs. This co-culture might be useful for epidermal differentiation of stem cells for future applications in skin regeneration.

Characterization of A Three-Dimensional Organotypic Co-Culture Skin Model for Epidermal Differentiation of Rat Adipose-Derived Stem Cells

PubMed Central

Ghanavati, Zeinab; Orazizadeh, Mahmoud; Bayati, Vahid; Abbaspour, Mohammad Reza; Khorsandi, Layasadat; Mansouri, Esrafil; Neisi, Niloofar

2016-01-01

Objective The organotypic co-culture is a well-known technique to examine cellular interactions and their roles in stem cell proliferation and differentiation. This study aims to evaluate the effects of dermal fibroblasts (DFs) on epidermal differentiation of adipose-derived stem cells (ASCs) using a three-dimensional (3D) organotypic co- culture technique. Materials and Methods In this experimental research study, rat DFs and ASCs were isolated and cultured separately on electrospun polycaprolactone (PCL) matrices. The PCL matrices seeded by ASCs were superimposed on to the matrices seeded by DFs in order to create a 3D organotypic co-culture. In the control groups, PCL matrices seeded by ASCs were placed on matrices devoid of DFs. After 10 days, we assessed the expressions of keratinocyte-related genes by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and expression of pan-cytokeratin protein by immunofluorescence in the differentiated keratinocyte-like cells from co- culture and control groups. Keratinocyte-like cell morphologies were also observed by scanning electron microscopy (SEM). Results The early, intermediate, and terminal differentiation keratinocyte markers-Cytokeratin14, Filaggrin, and Involucrin significantly expressed in the co-culture groups com- pared to the control ones (P<0.05). We observed pan-cytokeratin in keratinocyte-like cells of both groups by immunofluorescence. SEM observation of the co-culture groups showed that the differentiated keratinocyte-like cells developed a polygonal cobblestone shape, considered characteristic of keratinocytes. Conclusion The 3D organotypic co-culture bilayered construct that consisted of DFs and ASCs was an effective technique for epidermal differentiation of ASCs. This co-culture might be useful for epidermal differentiation of stem cells for future applications in skin regeneration. PMID:27602310

Effects of the Endocrine-Disrupting Chemical DDT on Self-Renewal and Differentiation of Human Mesenchymal Stem Cells

PubMed Central

Strong, Amy L.; Shi, Zhenzhen; Strong, Michael J.; Miller, David F.B.; Rusch, Douglas B.; Buechlein, Aaron M.; Flemington, Erik K.; McLachlan, John A.; Nephew, Kenneth P.

2014-01-01

Background: Although the global use of the endocrine-disrupting chemical DDT has decreased, its persistence in the environment has resulted in continued human exposure. Accumulating evidence suggests that DDT exposure has long-term adverse effects on development, yet the impact on growth and differentiation of adult stem cells remains unclear. Objectives: Human mesenchymal stem cells (MSCs) exposed to DDT were used to evaluate the impact on stem cell biology. Methods: We assessed DDT-treated MSCs for self-renewal, proliferation, and differentiation potential. Whole genome RNA sequencing was performed to assess gene expression in DDT-treated MSCs. Results: MSCs exposed to DDT formed fewer colonies, suggesting a reduction in self-renewal potential. DDT enhanced both adipogenic and osteogenic differentiation, which was confirmed by increased mRNA expression of glucose transporter type 4 (GLUT4), lipoprotein lipase (LpL), peroxisome proliferator-activated receptor gamma (PPARγ), leptin, osteonectin, core binding factor 1 (CBFA1), and FBJ murine osteosarcoma viral oncogene homolog (c-Fos). Expression of factors in DDT-treated cells was similar to that in estrogen-treated MSCs, suggesting that DDT may function via the estrogen receptor (ER)-mediated pathway. The coadministration of ICI 182,780 blocked the effects of DDT. RNA sequencing revealed 121 genes and noncoding RNAs to be differentially expressed in DDT-treated MSCs compared with controls cells. Conclusion: Human MSCs provide a powerful biological system to investigate and identify the molecular mechanisms underlying the effects of environmental agents on stem cells and human health. MSCs exposed to DDT demonstrated profound alterations in self-renewal, proliferation, differentiation, and gene expression, which may partially explain the homeostatic imbalance and increased cancer incidence among those exposed to long-term EDCs. Citation: Strong AL, Shi Z, Strong MJ, Miller DF, Rusch DB, Buechlein AM, Flemington EK

Ethnic density and depressive symptoms among African Americans: threshold and differential effects across social and demographic subgroups.

PubMed

Bécares, Laia; Nazroo, James; Jackson, James

2014-12-01

We examined the association between Black ethnic density and depressive symptoms among African Americans. We sought to ascertain whether a threshold exists in the association between Black ethnic density and an important mental health outcome, and to identify differential effects of this association across social, economic, and demographic subpopulations. We analyzed the African American sample (n = 3570) from the National Survey of American Life, which we geocoded to the 2000 US Census. We determined the threshold with a multivariable regression spline model. We examined differential effects of ethnic density with random-effects multilevel linear regressions stratified by sociodemographic characteristics. The protective association between Black ethnic density and depressive symptoms changed direction, becoming a detrimental effect, when ethnic density reached 85%. Black ethnic density was protective for lower socioeconomic positions and detrimental for the better-off categories. The masking effects of area deprivation were stronger in the highest levels of Black ethnic density. Addressing racism, racial discrimination, economic deprivation, and poor services-the main drivers differentiating ethnic density from residential segregation-will help to ensure that the racial/ethnic composition of a neighborhood is not a risk factor for poor mental health.

Ethnic Density and Depressive Symptoms Among African Americans: Threshold and Differential Effects Across Social and Demographic Subgroups

PubMed Central

Nazroo, James; Jackson, James

2014-01-01

Objectives. We examined the association between Black ethnic density and depressive symptoms among African Americans. We sought to ascertain whether a threshold exists in the association between Black ethnic density and an important mental health outcome, and to identify differential effects of this association across social, economic, and demographic subpopulations. Methods. We analyzed the African American sample (n = 3570) from the National Survey of American Life, which we geocoded to the 2000 US Census. We determined the threshold with a multivariable regression spline model. We examined differential effects of ethnic density with random-effects multilevel linear regressions stratified by sociodemographic characteristics. Results. The protective association between Black ethnic density and depressive symptoms changed direction, becoming a detrimental effect, when ethnic density reached 85%. Black ethnic density was protective for lower socioeconomic positions and detrimental for the better-off categories. The masking effects of area deprivation were stronger in the highest levels of Black ethnic density. Conclusions. Addressing racism, racial discrimination, economic deprivation, and poor services—the main drivers differentiating ethnic density from residential segregation—will help to ensure that the racial/ethnic composition of a neighborhood is not a risk factor for poor mental health. PMID:25322307

Effect of citrus flavonoids on HL-60 cell differentiation.

PubMed

Kawaii, S; Tomono, Y; Katase, E; Ogawa, K; Yano, M

1999-01-01

Twenty-seven Citrus flavonoids were examined for their activity of induction of terminal differentiation of human promyelocytic leukemia cells (HL-60) by nitro blue tetrazolium (NBT) reducing, nonspecific esterase, specific esterase, and phagocytic activities. 10 flavonoids were judged to be active (percentage of NBT reducing cells was more than 40% at a concentration of 40 microM), and the rank order of potency was natsudaidain, luteolin, tangeretin, quercetin, apigenin, 3, 3, '4, '5, 6, 7, 8-heptamethoxyflavone, nobiletin, acacetin, eriodictyol, and taxifolin. These flavonoids exerted their activity in a dose-dependent manner. HL-60 cells treated with these flavonoids differentiated into mature monocyte/macrophage. The structure-activity relationship established from comparison between flavones and flavanones revealed that ortho-catechol moiety in ring B and C2-C3 double bond had an important role for induction of differentiation of HL-60. In polymethoxylated flavones, hydroxyl group at C3 and methoxyl group at C8 enhanced the differentiation-inducing activity.

Effect of differential speed rolling on the texture evolution of Mg-4Zn-1Gd alloy

NASA Astrophysics Data System (ADS)

Shim, Myeong-Shik; Suh, Byeong-Chan; Kim, Jae H.; Kim, Nack J.

2015-05-01

The microstructural and texture evolution during differential speed rolling process of Mg 4Zn-1Gd (wt%) alloy have been investigated by means of electron backscatter diffraction observation and texture analysis. The angular distribution of basal poles are inclined about 10° from the normal direction towards the rolling direction and the maximum intensities of basal poles are decreased, compared to the conventional rolling process. Such an inclination of angular distribution of basal poles can be induced by the operation of shear stress along the rolling direction, as much as one quarter of tensile stress along the RD and one quarter of compressive stress along the ND. When the reduction ratios in differential speed rolling increase, there is no difference in texture evolution although there is a significant change in activated twinning systems. In addition, the engineering stresses after differential speed rolling are also similar to that after conventional rolling process, while ductility and stretch formability in the former are worse than those in the latter.

Inhibitory effect of leptin on rosiglitazone-induced differentiation of primary adipocytes prepared from TallyHO/Jng mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Ki Young; Kim, Joo Young; Sung, Yoon-Young

2011-03-25

Research highlights: {yields} In this study, we investigated the effects of leptin on adipocyte differentiation prepared from subcutaneous fat of TallyHo mice. {yields} Leptin inhibited the adipocytes differentiation at physiological concentration via inhibition of PPAR{gamma} expression. {yields} Inhibitors of ERK and STAT1 restored the leptin's inhibitory activity both in vitro and in vivo. -- Abstract: The effects of leptin on rosiglitazone-induced adipocyte differentiation were investigated in the primary adipocytes prepared from subcutaneous fat of TallyHO/Jng (TallyHO) mouse, a recently developed model animal for type 2 diabetes mellitus (T2DM). The treatment of leptin inhibited the rosiglitazone-induced adipocyte differentiation with a decreasedmore » expression of peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) a key adipogenic transcription factor, both in mRNA and protein levels. Leptin (10 nM) was sufficient to inhibit the adipocyte differentiation, which seemed to come from increased expression of leptin receptor genes in the fat of TallyHO mice. The inhibition of adipogenesis by leptin was restored by the treatment of inhibitors for extracellular-signal-regulated kinase (ERK) (PD98059) and signal transducer and activator of transcription-1 (STAT1) (fludarabine). Furthermore, in vivo intraperitoneal administration of PD98059 and fludarabine increased the PPAR{gamma} expression in the subcutaneous fat of TallyHO mice. These data suggest that leptin could inhibit the PPAR{gamma} expression and adipocyte differentiation in its physiological concentration in TallyHO mice.« less

Sex-differential heterologous (non-specific) effects of vaccines: an emerging public health issue that needs to be understood and exploited.

PubMed

Flanagan, Katie L; Plebanski, Magdalena

2017-01-01

Vaccines have heterologous effects on the immune system, leading to altered susceptibility to a range of pathogens, and possibly allergy and autoimmunity. Effects are often sex-differential. This review discusses the evidence, mechanisms and public health implications of the non-specific effects of vaccines (NSEs). Areas covered: This article firstly discusses the World Health Organization systematic review of the evidence for sex-differential heterologous effects of vaccines, and further PubMed indexed studies on NSEs on susceptibility to infectious diseases, allergy, autoimmunity and malignancy in animals and humans. Potential immunological mechanisms are evaluated, including sex-differential effects. Finally it describes how advances in systems biology might be applied to study such effects. Expert commentary: This section points out the need to understand immune mechanisms in order to exploit beneficial vaccine effects, and diminish deleterious ones. It suggests analysis of vaccine effects by sex is important, and discusses the future for personalised vaccines that take these effects into account.

Differential growth of wrinkled biofilms

NASA Astrophysics Data System (ADS)

Espeso, D. R.; Carpio, A.; Einarsson, B.

2015-02-01

Biofilms are antibiotic-resistant bacterial aggregates that grow on moist surfaces and can trigger hospital-acquired infections. They provide a classical example in biology where the dynamics of cellular communities may be observed and studied. Gene expression regulates cell division and differentiation, which affect the biofilm architecture. Mechanical and chemical processes shape the resulting structure. We gain insight into the interplay between cellular and mechanical processes during biofilm development on air-agar interfaces by means of a hybrid model. Cellular behavior is governed by stochastic rules informed by a cascade of concentration fields for nutrients, waste, and autoinducers. Cellular differentiation and death alter the structure and the mechanical properties of the biofilm, which is deformed according to Föppl-Von Kármán equations informed by cellular processes and the interaction with the substratum. Stiffness gradients due to growth and swelling produce wrinkle branching. We are able to reproduce wrinkled structures often formed by biofilms on air-agar interfaces, as well as spatial distributions of differentiated cells commonly observed with B. subtilis.

Effect of castration on carcass quality and differential gene expression of longissimus muscle between steer and bull.

PubMed

Zhou, Zheng-Kui; Gao, Xue; Li, Jun-Ya; Chen, Jin-Bao; Xu, Shang-Zhong

2011-11-01

The effect of castration on carcass quality was investigated by ten Chinese Simmental calves. Five calves were castrated randomly at 2 months old and the others were retained as normal intact bulls. All animals were slaughtered at 22 months old. The results showed that bulls carcass had higher weight (P < 0.05), dressing percentages and bigger longissimus muscle areas (P < 0.05) than steers. But steer meat had lower shear force values and was fatter (P < 0.05) than bull. Furthermore, in order to discover genes that were involved in determining steer meat quality, we compared related candidate gene expression in longissimus muscle between steer (tester) and bull (driver) using suppressive subtractive hybridization. Ten genes were identified as preferentially expressed in longissimus muscle of steer. The expression of four selected differentially expressed genes was confirmed by quantitative real-time PCR. Overall, a 1.96, 2.41, 2.89, 2.41-fold increase in expression level was observed in steer compared with bull for actin, gamma 2, smooth muscle, tropomyosin-2, insulin like growth factor 1 and hormone-sensitive lipase, respectively. These results implied that these differentially expressed genes could play an important role in the regulation of steer meat quality.

The effect of long-term corticosterone treatment on blood cell differentials and function in laboratory and wild-caught amphibian models.

PubMed

Falso, Paul G; Noble, Christopher A; Diaz, Jesus M; Hayes, Tyrone B

2015-02-01

The effect of long-term stress on amphibian immunity is not well understood. We modeled a long-term endocrine stress scenario by elevating plasma corticosterone in two species of amphibians and examined effects on white blood cell differentials and innate immune activity. Plasma corticosterone was elevated in American bullfrogs (Lithobates catesbeianus) by surgically implanting corticosterone capsules and in African clawed frogs (Xenopus laevis) by immersion in corticosterone-treated water. To provide a context for our results within endogenous corticosterone fluctuations, diurnal plasma corticosterone cycles were determined. A daily low of corticosterone was observed in X. laevis at 12:00, while a significant pattern was not observed in L. catesbeianus. Elevated plasma corticosterone levels increased the ratio of peripheral neutrophils to lymphocytes, in both species, and decreased eosinophil concentrations in L. catesbeianus over a long-term period. Whole blood oxidative burst generally correlated with neutrophil concentrations, and thus was increased with corticosterone treatment, significantly in L. catesbeianus. In L. catesbeianus, an endogenous response of eosinophils and lymphocytes to implanted empty (sham) capsules was observed, but this effect was attenuated by corticosterone. Peripheral monocyte and basophil concentrations were not significantly altered by corticosterone treatment in either species. Our results show that long-term stress can alter amphibian immune parameters for extended periods and may play a role in susceptibility to disease. Copyright © 2015 Elsevier Inc. All rights reserved.

The effects of differential and variable training on the quality parameters of a handball throw.

PubMed

Wagner, Herbert; Müller, Erich

2008-01-01

The aim of this study was to undertake a comprehensive temporal, effective, and practical training study (variable and differential learning) that would offer athletes the opportunity to increase their performance, and to analyse the effects by measuring kinematics and quality parameters. Two participants of differing standards--a player of the first Austrian League and an Olympic and World Champion--but of similar anthropometric characteristics were recruited. One of the participants (Austrian League) was tested on five different occasions (pre-test and four retests) to measure the effects of four different training phases using kinematic analysis. The results of the study indicate an increase in ball velocity within the differential training phases (first, second, and fourth phases), different proximal-to-distal sequences of the participants, and a change of movement pattern during training measured by the segment velocities and the angle-time courses.

The influence of cell interactions and tissue mass on differentiation of sea urchin mesomeres.

PubMed

Khaner, O; Wilt, F

1990-07-01

The developmental potential of different blastomeres of the sea urchin embryo was re-examined. We have employed a new method to isolate substantial numbers of different kinds of blastomeres from 16-cell-stage embryos, and we have used newly available molecular markers to analyze possible vegetal differentiation. We have found that, while isolated mesomere pairs behave according to the classical expectations and develop into ectodermal vesicles, there is a clear effect of reaggregating two or more mesomere pairs. They survive better in long-term culture and, after prolonged periods, they display an astonishing ability to express vegetal differentiation. We also combined mesomeres with stained micromeres or macromeres from the vegetal hemisphere. Although induction of guts and spicules was observed, there was little if any effect of varying the ratio of different blastomeres on the kinds of differentiation obtained.

Differential effects of centrally-administered oestrogen antagonist ICI-182,780 on oestrogen-sensitive functions in the hypothalamus.

PubMed

Steyn, F J; Anderson, G M; Grattan, D R

2007-01-01

Oestrogen actions within the hypothalamus are essential for a range of reproductive functions. In this study, we sought to develop a method for suppressing central oestrogen action without affecting peripheral oestrogenic effects. We administered the oestrogen receptor antagonist ICI-182,780 (ICI) via crystalline implants into the left lateral ventricle or the arcuate nucleus and measured the effectiveness of this drug on three endpoints known to be regulated by oestrogen: gonadotrophin-releasing hormone (GnRH) pulse frequency, progesterone receptor expression and the generation of a sustained prolactin surge during late pregnancy. To confirm that central ICI administration had no effect on peripheral actions of oestrogen, we monitored changes in uterine weight. Intracerebroventricular ICI treatment reversed the inhibitory effects of oestrogen on GnRH pulse frequency, as measured by plasma luteinising hormone pulse frequency. No effect on the oestrogenic induction of progesterone receptors within the arcuate nucleus or ventromedial hypothalamus was observed; however, a small yet significant reduction in progesterone receptor expression within dopaminergic neurones in the arcuate nucleus was observed. Intracerebroventricular or direct crystalline ICI administration to the arcuate nucleus did not change the serum prolactin level during late pregnancy. Central administration of ICI did not affect uterine weight, and thus did not have a peripheral effect. These data suggest that central administration of ICI can overcome some actions of oestrogen in the brain, such as GnRH pulse frequency, but does not affect other oestrogen mediated actions, including the induction of progesterone receptors or the antepartum prolactin surge. Thus, it appears that there is a differential sensitivity to the inhibition of central oestrogen actions by ICI.

Effects of VEGF-ANG-1-PLA nano-sustained release microspheres on proliferation and differentiation of ADSCs.

PubMed

He, Yucang; Li, Zihao; Chen, Zhuojie; Yu, Xiaofang; Ji, Ziwan; Wang, Jingping; Qian, Yao; Li, Liqun

2018-05-10

The improvement of fat graft viability might depend on the presence of multipotent resident adipose derived stem cells (ADSCs) which is the important component of stromal vascular fraction (SVF). Vascular endothelial growth factor (VEGF) and angiogenin-1 (Ang-1) are responsible for neovascularization. However, their half-life is too short to produce a biological effect. We thus investigated whether VEGF-ANG-1-polylactic acid (PLA) microspheres could enhance the angiogenic properties of ADSCs. PLA microspheres containing VEGF and ANG-1 were prepared by in vitro ultrasonic emulsification and characterized according to their encapsulation efficiency (EE), drug-loading rate (DL), particle size and drug release. The systemic toxicity of empty loaded nanospheres (NPs) and the ability of these microspheres to promote the proliferation and differentiation of ADSCs were evaluated. The EE and DL were above 86% and 2.8%, respectively. The drug release was completed after 20 days. Systemic toxicity was verified in ADSCs that received the unloaded NPs. It was observed that ADSCs treated with VEGF-ANG-1-PLA microspheres had an increase in the proliferation and the number of CD31 positive cells. ADSCs proliferation and differentiation toward endothelial cells (ECs) could be enhanced by the addition of VEGF-ANG-1-PLA nano-sustained release microspheres. This article is protected by copyright. All rights reserved.

Combined effects of chemical priming and mechanical stimulation on mesenchymal stem cell differentiation on nanofiber scaffolds

PubMed Central

Subramony, Siddarth D.; Su, Amanda; Yeager, Keith; Lu, Helen H.

2014-01-01

Functional tissue engineering of connective tissues such as the anterior cruciate ligament (ACL) remains a significant clinical challenge, largely due to the need for mechanically competent scaffold systems for grafting, as well as a reliable cell source for tissue formation. We have designed an aligned, polylactide-co-glycolide (PLGA) nanofiber-based scaffold with physiologically relevant mechanical properties for ligament regeneration. The objective of this study is to identify optimal tissue engineering strategies for fibroblastic induction of human mesenchymal stem cells (hMSC), testing the hypothesis that basic fibroblast growth factor (bFGF) priming coupled with tensile loading will enhance hMSC-mediated ligament regeneration. It was observed that compared to the unloaded, as well as growth factor-primed but unloaded controls, bFGF stimulation followed by physiologically relevant tensile loading enhanced hMSC proliferation, collagen production and subsequent differentiation into ligament fibroblast-like cells, upregulating the expression of types I and III collagen, as well as tenasin-C and tenomodulin. The results of this study suggest that bFGF priming increases cell proliferation, while mechanical stimulation of the hMSCs on the aligned nanofiber scaffold promotes fibroblastic induction of these cells. In addition to demonstrating the potential of nanofiber scaffolds for hMSC-mediated functional ligament tissue engineering, this study yields new insights into the interactive effects of chemical and mechanical stimuli on stem cell differentiation. PMID:24267271

Delay in Apoptosome Formation Attenuates Apoptosis in Mouse Embryonic Stem Cell Differentiation

PubMed Central

Akbari-Birgani, Shiva; Hosseinkhani, Saman; Mollamohamadi, Sepideh; Baharvand, Hossein

2014-01-01

Differentiation is an inseparable process of development in multicellular organisms. Mouse embryonic stem cells (mESCs) represent a valuable research tool to conduct in vitro studies of cell differentiation. Apoptosis as a well known cell death mechanism shows some common features with cell differentiation, which has caused a number of ambiguities in the field. The research question here is how cells could differentiate these two processes from each other. We have investigated the role of the mitochondrial apoptotic pathway and cell energy level during differentiation of mESCs into the cardiomyocytes and their apoptosis. p53 expression, cytochrome c release, apoptosome formation, and caspase-3/7 activation are observed upon induction of both apoptosis and differentiation. However, remarkable differences are detected in time of cytochrome c appearance, apoptosome formation, and caspase activity upon induction of both processes. In apoptosis, apoptosome formation and caspase activity were observed rapidly following the cytochrome c release. Unlike apoptosis, the release of cytochrome c upon differentiation took more time, and the maximum caspase activity was also postponed for 24 h. This delay suggests that there is a regulatory mechanism during differentiation of mESCs into cardiomyocytes. The highest ATP content of cells was observed immediately after cytochrome c release 6 h after apoptosis induction and then decreased, but it was gradually increased up to 48 h after differentiation. These observations suggest that a delay in the release of cytochrome c or delay in ATP increase attenuate apoptosome formation, and caspase activation thereby discriminates apoptosis from differentiation in mESCs. PMID:24755221

Comparative Effect of Physicomechanical and Biomolecular Cues on Zone-Specific Chondrogenic Differentiation of Mesenchymal Stem Cells

PubMed Central

Moeinzadeh, Seyedsina; Shariati, Seyed Ramin Pajoum; Jabbari, Esmaiel

2016-01-01

Current tissue engineering approaches to regeneration of articular cartilage rarely restore the tissue to its normal state because the generated tissue lacks the intricate zonal organization of the native cartilage. Zonal regeneration of articular cartilage is hampered by the lack of knowledge for the relation between physical, mechanical, and biomolecular cues and zone-specific chondrogenic differentiation of progenitor cells. This work investigated in 3D the effect of TGF-β1, zone-specific growth factors, optimum matrix stiffness, and adding nanofibers on the expression of chondrogenic markers specific to the superficial, middle, and calcified zones of articular cartilage by the differentiating human mesenchymal stem cells (hMSCs). Growth factors included BMP-7, IGF-1, and hydroxyapatite (HA) for the superficial, middle, and calcified zones, respectively; optimum matrix stiffness was 80 kPa, 2.1 MPa, and 320 MPa; and nanofibers were aligned horizontal, random, and perpendicular to the gel surface. hMSCs with zone-specific cell densities were encapsulated in engineered hydrogels and cultured with or without TGF-β1, zone-specific growth factor, optimum matrix modulus, and fiber addition and cultured in basic chondrogenic medium. The expression of encapsulated cells was measured by mRNA, protein, and biochemical analysis. Results indicated that zone-specific matrix stiffness had a dominating effect on chondrogenic differentiation of hMSCs to the superficial and calcified zone phenotypes. Addition of aligned nanofibers parallel to the direction of gel surface significantly enhanced expression of Col II in the superficial zone chondrogenic differentiation of hMSCs. Conversely, biomolecular factor IGF-1 in combination with TGF-β1 had a dominating effect on the middle zone chondrogenic differentiation of hMSCs. Results of this work could potentially lead to the development of multilayer grafts mimicking the zonal organization of articular cartilage. PMID:27038568

Adjuvant Effect of Killed Propionibacterium acnes on Mouse Peritoneal B-1 Lymphocytes and Their Early Phagocyte Differentiation

PubMed Central

Mussalem, Juliana Sekeres; Squaiella-Baptistão, Carla Cristina; Teixeira, Daniela; Yendo, Tatiana Mina; Thies, Felipe Garutti; Popi, Ana Flavia; Mariano, Mario; Longo-Maugéri, Ieda

2012-01-01

B-1 lymphocytes are the predominant cells in mouse peritoneal cavity. They express macrophage and lymphocyte markers and are divided into B-1a, B-1b and B-1c subtypes. The role of B-1 cells is not completely clear, but they are responsible for natural IgM production and seem to play a regulatory role. An enriched B-1b cell population can be obtained from non-adherent peritoneal cell cultures, and we have previously demonstrated that these cells undergo differentiation to acquire a mononuclear phagocyte phenotype upon attachment to the substrate in vitro. Nevertheless, the B-1 cell response to antigens or adjuvants has been poorly investigated. Because killed Propionibacterium acnes exhibits immunomodulatory effects on both macrophages and B-2 lymphocytes, we analyzed whether a killed bacterial suspension or its soluble polysaccharide (PS) could modulate the absolute number of peritoneal B-1 cells in BALB/c mice, the activation status of these cells and their ability to differentiate into phagocytes in vitro. In vivo, P. acnes treatment elevated the absolute number of all B-1 subsets, whereas PS only increased B-1c. Moreover, the bacterium increased the number of B-1b cells that were positive for MHC II, TLR2, TLR4, TLR9, IL-4, IL-5 and IL-12, in addition to up-regulating TLR9, CD80 and CD86 expression. PS increased B-1b cell expression of TLR4, TLR9, CD40 and CD86, as well as IL-10 and IL-12 synthesis. Both of the treatments decreased the absolute number of B-1b cells in vitro, suggesting their early differentiation into B-1 cell-derived phagocytes (B-1CDP). We also observed a higher phagocytic activity from the phagocytes that were derived from B-1b cells after P. acnes and PS treatment. The adjuvant effect that P. acnes has on B-1 cells, mainly the B-1b subtype, reinforces the importance of B-1 cells in the innate and adaptive immune responses. PMID:22448280

Adjuvant effect of killed Propionibacterium acnes on mouse peritoneal B-1 lymphocytes and their early phagocyte differentiation.

PubMed

Mussalem, Juliana Sekeres; Squaiella-Baptistão, Carla Cristina; Teixeira, Daniela; Yendo, Tatiana Mina; Thies, Felipe Garutti; Popi, Ana Flavia; Mariano, Mario; Longo-Maugéri, Ieda

2012-01-01

B-1 lymphocytes are the predominant cells in mouse peritoneal cavity. They express macrophage and lymphocyte markers and are divided into B-1a, B-1b and B-1c subtypes. The role of B-1 cells is not completely clear, but they are responsible for natural IgM production and seem to play a regulatory role. An enriched B-1b cell population can be obtained from non-adherent peritoneal cell cultures, and we have previously demonstrated that these cells undergo differentiation to acquire a mononuclear phagocyte phenotype upon attachment to the substrate in vitro. Nevertheless, the B-1 cell response to antigens or adjuvants has been poorly investigated. Because killed Propionibacterium acnes exhibits immunomodulatory effects on both macrophages and B-2 lymphocytes, we analyzed whether a killed bacterial suspension or its soluble polysaccharide (PS) could modulate the absolute number of peritoneal B-1 cells in BALB/c mice, the activation status of these cells and their ability to differentiate into phagocytes in vitro. In vivo, P. acnes treatment elevated the absolute number of all B-1 subsets, whereas PS only increased B-1c. Moreover, the bacterium increased the number of B-1b cells that were positive for MHC II, TLR2, TLR4, TLR9, IL-4, IL-5 and IL-12, in addition to up-regulating TLR9, CD80 and CD86 expression. PS increased B-1b cell expression of TLR4, TLR9, CD40 and CD86, as well as IL-10 and IL-12 synthesis. Both of the treatments decreased the absolute number of B-1b cells in vitro, suggesting their early differentiation into B-1 cell-derived phagocytes (B-1CDP). We also observed a higher phagocytic activity from the phagocytes that were derived from B-1b cells after P. acnes and PS treatment. The adjuvant effect that P. acnes has on B-1 cells, mainly the B-1b subtype, reinforces the importance of B-1 cells in the innate and adaptive immune responses.

Differentiated Staffing and Practice

ERIC Educational Resources Information Center

Christie, Kathy

2005-01-01

The development of the positions of nurse practitioner and physician assistant is a good example of differentiating staffing and practice to meet individual needs in an effective and cost-efficient way. This type of differentiation has been confined to the healthcare industry, principally to health maintenance organizations, but perhaps those in…

Effects of Differentiated Reading on Elementary Students' Reading Comprehension and Attitudes toward Reading

ERIC Educational Resources Information Center

Shaunessy-Dedrick, Elizabeth; Evans, Linda; Ferron, John; Lindo, Myriam

2015-01-01

In this investigation, we examined the effects of a differentiated reading approach on fourth grade students' reading comprehension and attitudes toward reading. Eight Title I schools within one urban district were randomly assigned to treatment (Schoolwide Enrichment Model-Reading [SEM-R]) or control (district reading curriculum) conditions.…

Heme oxygenase-1 affects generation and spontaneous cardiac differentiation of induced pluripotent stem cells.

PubMed

Stepniewski, Jacek; Pacholczak, Tomasz; Skrzypczyk, Aniela; Ciesla, Maciej; Szade, Agata; Szade, Krzysztof; Bidanel, Romain; Langrzyk, Agnieszka; Grochowski, Radoslaw; Vandermeeren, Felix; Kachamakova-Trojanowska, Neli; Jez, Mateusz; Drabik, Grazyna; Nakanishi, Mahito; Jozkowicz, Alicja; Dulak, Jozef

2018-02-01

Cellular stress can influence efficiency of iPSCs generation and their differentiation. However, the role of intracellular cytoprotective factors in these processes is still not well known. Therefore, we investigated the effect of HO-1 (Hmox1) or Nrf2 (Nfe2l2), two major cytoprotective genes. Hmox1 -/- fibroblasts demonstrated decreased reprogramming efficiency in comparison to Hmox1 +/+ cells. Reversely, pharmacological enhancement of HO-1 resulted in higher number of iPSCs colonies. Importantly, elevated level of both p53 and p53-regulated miR-34a and 14-3-3σ was observed in HO-1-deficient fibroblasts whereas downregulation of p53 in these cells markedly increased their reprogramming efficiency. In human fibroblasts HO-1 silencing also induced p53 expression and affected reprogramming outcome. Hmox1 +/+ and Hmox1 -/- iPSCs similarly differentiated in vitro to cells originating from three germ layers, however, lower number of contracting cells was observed during this process in HO-1-deficient cells indicating attenuated cardiac differentiation. Importantly, silencing of Hmox1 in murine ESC using CRISPR/Cas-9 editing also impaired their spontaneous cardiac differentiation. Decreased reprogramming efficiency was also observed in Nrf2-lacking fibroblasts. Reversely, sulforaphane, a Nrf2 activator, increased the number of iPSCs colonies. However, both Nfe2l2 +/+ and Nfe2l2 -/- iPSCs showed similar pluripotency and differentiation capacity. These results indicate that regulation of HO-1 expression can further optimize generation and cardiac differentiation of iPSCs. © 2018 IUBMB Life, 70(2):129-142, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

The Effect of Instrument-Specific Rater Training on Interrater Reliability and Counseling Skills Performance Differentiation

ERIC Educational Resources Information Center

Meacham, Paul Douglas, Jr.

2013-01-01

The purpose of this study was to explore the effect of instrument-specific rater training on interrater reliability (IRR) and counseling skills performance differentiation. Strong IRR is of primary concern to effective program evaluation (McCullough, Kuhn, Andrews, Valen, Hatch, & Osimo, 2003; Schanche, Nielsen, McCullough, Valen, &…

The differentiation history of the terrestrial planets as recorded on the moon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borg, L

2007-02-20

The outline for this report is: (1) Factors Leading to Lunar Magma Ocean Model for Planetary Differentiation (2) Rationale for Magma Oceans on Other Planets Means for early efficient differentiation (Works on Moon why not here?) (3) Some Inconsistencies between the Lunar Magma Ocean Model and Observations. The conclusions are: (1) Differentiation via solidification of a magma ocean is derived from geologic observations of the Moon (2) Although geologic observations on other bodies are often consistent with differentiation via magma ocean solidification, it is not generally required. (3) There are some fundamental inconsistencies between observed lunar data and the model,more » that will require this model to be modified (4) Nevertheless, the Moon is the only location we know of to study magma ocean process in detail.« less

Phase jitter in a differential phase experiment.

NASA Technical Reports Server (NTRS)

Tanenbaum, B. S.; Connolly, D. J.; Austin, G. L.

1973-01-01

Austin (1971) had concluded that, because of the 'phase jitter,' the differential phase experiment is useful over a more limited height range than the differential absorption experiment. Several observations are presented to show that this conclusion is premature. It is pointed out that the logical basis of the differential absorption experiment also requires that the O- and X-mode echoes, at a given time, come from the same irregularities. Austin's calculations are believed to contain a systematic error above 80 km.

Effect of restriction vegan diet's on muscle mass, oxidative status, and myocytes differentiation: A pilot study.

PubMed

Vanacore, Daniela; Messina, Giovanni; Lama, Stefania; Bitti, Giuseppe; Ambrosio, Pasqualina; Tenore, Giancarlo; Messina, Antonietta; Monda, Vincenzo; Zappavigna, Silvia; Boccellino, Mariarosaria; Novellino, Ettore; Monda, Marcellino; Stiuso, Paola

2018-01-10

This study was conceived to evaluate the effects of three different diets on body composition, metabolic parameters, and serum oxidative status. We enrolled three groups of healthy men (omnivores, vegetarians, and vegans) with similar age, weight and BMI, and we observed a significant decrease in muscle mass index and lean body mass in vegan compared to vegetarian and omnivore groups, and higher serum homocysteine levels in vegetarians and vegans compared to omnivores. We studied whether serum from omnivore, vegetarian, and vegan subjects affected oxidative stress, growth and differentiation of both cardiomyoblast cell line H9c2 and H-H9c2 (H9c2 treated with H 2 O 2 to induce oxidative damage). We demonstrated that vegan sera treatment of both H9c2 and H-H9c2 cells induced an increase of TBARS values and cell death and a decrease of free NO 2- compared to vegetarian and omnivorous sera. Afterwards, we investigated the protective effects of vegan, vegetarian, and omnivore sera on the morphological changes induced by H 2 O 2 in H9c2 cell line. We showed that the omnivorous sera had major antioxidant and differentiation properties compared to vegetarian and vegan sera. Finally, we evaluated the influence of the three different groups of sera on MAPKs pathway and our data suggested that ERK expression increased in H-H9c2 cells treated with vegetarian and vegan sera and could promote cell death. The results obtained in this study demonstrated that restrictive vegan diet could not prevent the onset of metabolic and cardiovascular diseases nor protect by oxidative damage. © 2018 Wiley Periodicals, Inc.

Effects of retinoids on differentiation, lipid metabolism, epidermal growth factor, and low-density lipoprotein binding in squamous carcinoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ponec, M.; Weerheim, A.; Havekes, L.

The relationship among keratinocyte differentiation capacity, lipid synthesis, low-density lipoprotein (LDL) metabolism, plasma membrane composition, and epidermal growth factor (EGF) binding has been studied in SCC-12F2 cells. The differentiation capacity of the cells, i.e., ionophore-induced cornified envelope formation, was inhibited by various retinoids and stimulated by hydrocortisone. Retinoids that caused a significant reduction of cornified envelope formation, i.e., retinoic acid and 13-cis-retinoic acid, caused only minor changes in lipid synthesis and plasma membrane composition. Arotinoid ethylsulfone, having a minor effect on cornified envelope formation, caused a drastic inhibition of cholesterol synthesis resulting in changes in the plasma membrane composition. Hydrocortisonemore » stimulated cornified envelope formation but had only minor effects on lipid synthesis and plasma membrane composition. Of all retinoids tested, only arotinoid ethylsulfone caused a drastic increase in EGF binding, while hydrocortisone had no effect. These results clearly demonstrate that the plasma membrane composition is not related to keratinocyte differentiation capacity, but most likely does determine EGF binding. Furthermore, EGF binding does not determine keratinocyte differentiation capacity.« less

Observational methods in comparative effectiveness research.

PubMed

Concato, John; Lawler, Elizabeth V; Lew, Robert A; Gaziano, J Michael; Aslan, Mihaela; Huang, Grant D

2010-12-01

Comparative effectiveness research (CER) may be defined informally as an assessment of available options for treating specific medical conditions in selected groups of patients. In this context, the most prominent features of CER are the various patient populations, medical ailments, and treatment options involved in any particular project. Yet, each research investigation also has a corresponding study design or "architecture," and in patient-oriented research a common distinction used to describe such designs are randomized controlled trials (RCTs) versus observational studies. The purposes of this overview, with regard to CER, are to (1) understand how observational studies can provide accurate results, comparable to RCTs; (2) recognize strategies used in selected newer methods for conducting observational studies; (3) review selected observational studies from the Veterans Health Administration; and (4) appreciate the importance of fundamental methodological principles when conducting or evaluating individual studies. Published by Elsevier Inc.

Vitamin E isomer δ-tocopherol enhances the efficiency of neural stem cell differentiation via L-type calcium channel.

PubMed

Deng, Sihao; Hou, Guoqiang; Xue, Zhiqin; Zhang, Longmei; Zhou, Yuye; Liu, Chao; Liu, Yanqing; Li, Zhiyuan

2015-01-12

The effects of the vitamin E isomer δ-tocopherol on neural stem cell (NSC) differentiation have not been investigated until now. Here we investigated the effects of δ-tocopherol on NSC neural differentiation, maturation and its possible mechanisms. Neonatal rat NSCs were grown in suspended neurosphere cultures, and were identified by their expression of nestin protein and their capacity for self-renewal. Treatment with a low concentration of δ-tocopherol induced a significant increase in the percentage of β-III-tubulin-positive cells. δ-Tocopherol also stimulated morphological maturation of neurons in culture. We further observed that δ-tocopherol stimulation increased the expression of voltage-dependent Ca(2+) channels. Moreover, a L-type specific Ca(2+) channel blocker verapamil reduced the percentage of differentiated neurons after δ-tocopherol treatment, and blocked the effects of δ-tocopherol on NSC differentiation into neurons. Together, our study demonstrates that δ-tocopherol may act through elevation of L-type calcium channel activity to increase neuronal differentiation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effect of hyperglycemia on the number of CD117+ progenitor cells and their differentiation toward endothelial progenitor cells in young and old ages.

PubMed

Pierpaoli, Elisa; Moresi, Raffaella; Orlando, Fiorenza; Malavolta, Marco; Provinciali, Mauro

2016-10-01

Dysfunction of endothelial progenitor cells (EPCs) has been reported either in aging or diabetes, though the influence of an "old" environment on numerical and functional changes of diabetes associated EPCs is not known. We evaluated the effect of both aging and early stage of streptozotocin-induced diabetes on the number of bone marrow-derived CD117 + progenitor cells, and on their differentiation in vitro toward EPCs. The phenotype of progenitor cells and the uptake of acetylated-low density lipoprotein (Ac-LDL) were evaluated after cell culture in VEGF, FGF-1, and IGF-1 supplemented medium. Hyperglycemia similarly reduced the number of CD117 + cells both in young and old mice. CD117 + cells from young mice differentiated better than those from old animals "in vitro", with a greater reduction of CD117 + cells and an higher increase of CD184 + VEGFR-2 + cells. In diabetic mice, in vitro CD117 + cells differentiation was significantly reduced in young animals. Diabetes did not impact on the scarce differentiation of CD117 + cells from old mice. Hyperglycemia reduced the uptake of acLDL by EPCs greatly in young than in old mice. These findings indicate that part of the EPCs functional alterations induced by hyperglicemia in young mice are observed in normal aged mice. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

DCGL v2.0: an R package for unveiling differential regulation from differential co-expression.

PubMed

Yang, Jing; Yu, Hui; Liu, Bao-Hong; Zhao, Zhongming; Liu, Lei; Ma, Liang-Xiao; Li, Yi-Xue; Li, Yuan-Yuan

2013-01-01

Differential co-expression analysis (DCEA) has emerged in recent years as a novel, systematic investigation into gene expression data. While most DCEA studies or tools focus on the co-expression relationships among genes, some are developing a potentially more promising research domain, differential regulation analysis (DRA). In our previously proposed R package DCGL v1.0, we provided functions to facilitate basic differential co-expression analyses; however, the output from DCGL v1.0 could not be translated into differential regulation mechanisms in a straightforward manner. To advance from DCEA to DRA, we upgraded the DCGL package from v1.0 to v2.0. A new module named "Differential Regulation Analysis" (DRA) was designed, which consists of three major functions: DRsort, DRplot, and DRrank. DRsort selects differentially regulated genes (DRGs) and differentially regulated links (DRLs) according to the transcription factor (TF)-to-target information. DRrank prioritizes the TFs in terms of their potential relevance to the phenotype of interest. DRplot graphically visualizes differentially co-expressed links (DCLs) and/or TF-to-target links in a network context. In addition to these new modules, we streamlined the codes from v1.0. The evaluation results proved that our differential regulation analysis is able to capture the regulators relevant to the biological subject. With ample functions to facilitate differential regulation analysis, DCGL v2.0 was upgraded from a DCEA tool to a DRA tool, which may unveil the underlying differential regulation from the observed differential co-expression. DCGL v2.0 can be applied to a wide range of gene expression data in order to systematically identify novel regulators that have not yet been documented as critical. DCGL v2.0 package is available at http://cran.r-project.org/web/packages/DCGL/index.html or at our project home page http://lifecenter.sgst.cn/main/en/dcgl.jsp.

Delphinidin, a dietary antioxidant, induces human epidermal keratinocyte differentiation but not apoptosis: studies in submerged and three-dimensional epidermal equivalent models.

PubMed

Chamcheu, Jean Christopher; Afaq, Farrukh; Syed, Deeba N; Siddiqui, Imtiaz A; Adhami, Vaqar M; Khan, Naghma; Singh, Sohinderjit; Boylan, Brendan T; Wood, Gary S; Mukhtar, Hasan

2013-05-01

Delphinidin (Del), [3,5,7,3'-,4'-,5'-hexahydroxyflavylium], an anthocyanidin and a potent antioxidant abundantly found in pigmented fruits and vegetables exhibits proapoptotic effects in many cancer cells. Here, we determined the effect of Del on growth, apoptosis and differentiation of normal human epidermal keratinocytes (NHEKs) in vitro in submerged cultures and examined its effects in a three-dimensional (3D) epidermal equivalent (EE) model that permits complete differentiation reminiscent of in vivo skin. Treatment of NHEKs with Del (10-40 μm; 24-48 h) significantly enhanced keratinocyte differentiation. In Del-treated cells, there was marked increase in human involucrin (hINV) promoter activity with simultaneous increase in the mRNA and protein expressions of involucrin and other epidermal differentiation markers including procaspase-14 and transglutaminase-1 (TGM1), but without any effect on TGM2. Del treatment of NHEKs was associated with minimal decrease in cell viability, which was not associated with apoptosis as evident by lack of modulation of caspases, apoptosis-related proteins including Bcl-2 family of proteins and poly(ADP-ribose) polymerase cleavage. To establish the in vivo relevance of our observations in submerged cultures, we then validated these effects in a 3D EE model, where Del was found to significantly enhance cornification and increase the protein expression of cornification markers including caspase-14 and keratin 1. For the first time, we show that Del induces epidermal differentiation using an experimental system that closely mimics in vivo human skin. These observations suggest that Del could be a useful agent for dermatoses associated with epidermal barrier defects including aberrant keratinization, hyperproliferation or inflammation observed in skin diseases like psoriasis and ichthyoses. © 2013 John Wiley & Sons A/S.

[Effects of different mechanical stretch conditions on differentiation of rat tendon stem cells].

PubMed

Li, Pao; Gao, Shang; Zhou, Mei; Tang, Hong; Mu, Miduo; Zhang, Jiqiang; Tang, Kanglai

2017-04-01

To investigate the effects of different mechanical stretch conditions on the differentiation of rat tendon stem cells (TSCs), to find the best uniaxial cyclic stretching for TSCs tenogenic differentiation, osteogenic differentiation, and adipogenic differentiation. TSCs were isolated from the Achilles tendons of 8-week-old male Sprague Dawley rats by enzymatic digestion method and cultured. The TSCs at passage 3 were randomly divided into 5 groups: group A (stretch strength of 4% and frequency of 1 Hz), group B (stretch strength of 4% and frequency of 2 Hz), group C (stretch strength of 8% and frequency of 1 Hz), group D (stretch strength of 8% and frequency of 2 Hz), and group E (static culture). At 12, 24, and 48 hours after mechanical stretch, the mRNA expressions of the tenogenic differentiation related genes [Scleraxis (SCX) and Tenascin C (TNC)], the osteogenic differentiation related genes [runt related transcription factor 2 (RUNX2) and distal-less homeobox 5 (DLX5)], and the adipogenic differentiation related genes [CCAAT-enhancer-binding protein-α (CEBPα) and lipoprteinlipase (LPL)] were detected by real-time fluorescent quantitative PCR and the protein expressions of TNC, CEBPα, and RUNX2 were detected by Western blot. The mRNA expressions of SCX and TNC in group B were significantly higher than those in groups A, C, D, and E at 24 hours after mechanical stretch ( P <0.05). The mRNA expressions of CEBPα and LPL in group D were significantly higher than those in groups A, B, C, and E at 48 hours after mechanical stretch ( P <0.05). The mRNA expressions of RUNX2 and DLX5 in group C were significantly higher than those in groups A, B, D, and E at 24 hours after mechanical stretch ( P <0.05). Western blot detection showed that higher protein expression of TNC in group B than group E at each time point after mechanical stretch ( P <0.05), and the protein expression of CEBPα was significantly inhibited when compared with group E at 24 hours after

Effects of cellular differentiation, chromosomal integration and 5-aza-2'-deoxycytidine treatment on human papillomavirus-16 DNA methylation in cultured cell lines.

PubMed

Kalantari, Mina; Lee, Denis; Calleja-Macias, Itzel E; Lambert, Paul F; Bernard, Hans-Ulrich

2008-05-10

Human papillomavirus-16 (HPV-16) genomes in cell culture and in situ are affected by polymorphic methylation patterns, which can repress the viral transcription. In order to understand some of the underlying mechanisms, we investigated changes of the methylation of HPV-16 DNA in cell cultures in response to cellular differentiation, to recombination with cellular DNA, and to an inhibitor of methylation. Undifferentiated W12E cells, derived from a precancerous lesion, contained extrachromosomal HPV-16 DNA with a sporadically methylated enhancer-promoter segment. Upon W12E cell differentiation, the viral DNA was demethylated, suggesting a link between differentiation and the epigenetic state of HPV-16 DNA. The viral genomes present in two W12I clones, in which individual copies of the HPV-16 genome have integrated into cellular DNA (type 1 integrants), were unmethylated, akin to that seen in the cervical carcinoma cell line SiHa (also a type 1 integrant). This finding is consistent with hypomethylation being necessary for continued viral gene expression. In contrast, two of three type 2 integrant W12I clones, containing concatemers of HPV-16 genomes integrated into the cellular DNA contained hypermethylated viral DNA, as observed in the cervical carcinoma cell line CaSki (also a type 2 integrant). A third, type 2, W12I clone, interestingly with fewer copies of the viral genome, contained unmethylated HPV-16 genomes. Epithelial differentiation of W12I clones did not lead to demethylation of chromosomally integrated viral genomes as was seen for extrachromosomal HPV-16 DNA in W12E clones. Hypomethylation of CaSki cells in the presence of the DNA methylation inhibitor 5-aza-2'-deoxycytidine reduced the cellular viability, possibly as a consequence of toxic effects of an excess of HPV-16 gene products. Our data support a model wherein (i) the DNA methylation state of extrachromosomal HPV16 replicons and epithelial differentiation are inversely coupled during the viral

Effects of differentiation on the geodynamics of the early Earth

NASA Astrophysics Data System (ADS)

Piccolo, Andrea; Kaus, Boris; White, Richard; Johnson, Tim

2016-04-01

Archean geodynamic processes are not well understood, but there is general agreement that the mantle potential temperature was higher than present, and that as a consequence significant amounts of melt were produced both in the mantle and any overlying crust. This has likely resulted in crustal differentiation. An early attempt to model the geodynamic effects of differentiation was made by Johnson et al. (2014), who used numerical modeling to investigate the crust production and recycling in conjunction with representative phase diagrams (based on the inferred chemical composition of the primary melt in accordance with the Archean temperature field). The results of the simulations show that the base of the over-thickened primary basaltic crust becomes gravitational unstable due to the mineral assemblage changes. This instability leads to the dripping of dense material into the mantle, which causes an asthenospheric return flow, local partial melting and new primary crust generation that is rapidly recycled in to mantle. Whereas they gave important insights, the previous simulations were simplified in a number of aspects: 1) the rheology employed was viscous, and both elasticity and pressure-dependent plasticity were not considered; 2) extracted mantle melts were 100% transformed into volcanic rocks, whereas on the present day Earth only about 20-30% are volcanic and the remainder is plutonic; 3) the effect of a free surface was not studied in a systematic manner. In order to better understand how these simplifications affect the geodynamic models, we here present additional simulations to study the effects of each of these parameters. Johnson, T.E., Brown, M., Kaus, B., and VanTongeren, J.A., 2014, Delamination and recycling of Archaean crust caused by gravitational instabilities: Nature Geoscience, v. 7, no. 1, p. 47-52, doi: 10.1038/NGEO2019.

Differential effects on cell motility, embryonic stem cell self-renewal and senescence by diverse Src kinase family inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tamm, Christoffer, E-mail: christoffer.tamm@imbim.uu.se; Galito, Sara Pijuan, E-mail: sara.pijuan@imbim.uu.se; Anneren, Cecilia, E-mail: cecilia.anneren@imbim.uu.se

2012-02-15

The Src family of non-receptor tyrosine kinases (SFKs) has been shown to play an intricate role in embryonic stem (ES) cell maintenance. In the present study we have focused on the underlying molecular mechanisms responsible for the vastly different effects induced by various commonly used SFK inhibitors. We show that several diverse cell types, including fibroblasts completely lacking SFKs, cannot undergo mitosis in response to SU6656 and that this is caused by an unselective inhibition of Aurora kinases. In contrast, PP2 and PD173952 block motility immediately upon exposure and forces cells to grow in dense colonies. The subsequent halt inmore » proliferation of fibroblast and epithelial cells in the center of the colonies approximately 24 h post-treatment appears to be caused by cell-to-cell contact inhibition rather than a direct effect of SFK kinase inhibition. Interestingly, in addition to generating more homogenous and dense ES cell cultures, without any diverse effect on proliferation, PP2 and PD173652 also promote ES cell self-renewal by reducing the small amount of spontaneous differentiation typically observed under standard ES cell culture conditions. These effects could not be mirrored by the use of Gleevec, a potent inhibitor of c-Abl and PDGFR kinases that are also inhibited by PP2. -- Highlights: Black-Right-Pointing-Pointer SFK inhibitor SU6656 induces senescence in mouse ES cells. Black-Right-Pointing-Pointer SU6656 inhibits mitosis in a SFK-independent manner via cross-selectivity for Aurora kinases. Black-Right-Pointing-Pointer SFK inhibitor PP2 impairs cell motility in various cell lines, including mouse ES cells. Black-Right-Pointing-Pointer Ensuing impeded motility, PP2 inhibits proliferation of various cells lines except for mouse ES cells. Black-Right-Pointing-Pointer SFK inhibitors PP2 and PD173952 impede spontaneous differentiation in standard mouse ES culture maintenance.« less

Gender-Differentiated Parenting Revisited: Meta-Analysis Reveals Very Few Differences in Parental Control of Boys and Girls

PubMed Central

Endendijk, Joyce J.; Groeneveld, Marleen G.; Bakermans-Kranenburg, Marian J.; Mesman, Judi

2016-01-01

Although various theories describe mechanisms leading to differential parenting of boys and girls, there is no consensus about the extent to which parents do treat their sons and daughters differently. The last meta-analyses on the subject were conducted more than fifteen years ago, and changes in gender-specific child rearing in the past decade are quite plausible. In the current set of meta-analyses, based on 126 observational studies (15,034 families), we examined mothers’ and fathers’ differential use of autonomy-supportive and controlling strategies with boys and girls, and the role of moderators related to the decade in which the study was conducted, the observational context, and sample characteristics. Databases of Web of Science, ERIC, PsychInfo, Online Contents, Picarta, and Proquest were searched for studies examining differences in observed parental control of boys and girls between the ages of 0 and 18 years. Few differences were found in parents’ use of control with boys and girls. Parents were slightly more controlling with boys than with girls, but the effect size was negligible (d = 0.08). The effect was larger, but still small, in normative groups and in samples with younger children. No overall effect for gender-differentiated autonomy-supportive strategies was found (d = 0.03). A significant effect of time emerged: studies published in the 1970s and 1980s reported more autonomy-supportive strategies with boys than toward girls, but from 1990 onwards parents showed somewhat more autonomy-supportive strategies with girls than toward boys. Taking into account parents’ gender stereotypes might uncover subgroups of families where gender-differentiated control is salient, but based on our systematic review of the currently available large data base we conclude that in general the differences between parenting of boys versus girls are minimal. PMID:27416099

Gender-Differentiated Parenting Revisited: Meta-Analysis Reveals Very Few Differences in Parental Control of Boys and Girls.

PubMed

Endendijk, Joyce J; Groeneveld, Marleen G; Bakermans-Kranenburg, Marian J; Mesman, Judi

2016-01-01

Although various theories describe mechanisms leading to differential parenting of boys and girls, there is no consensus about the extent to which parents do treat their sons and daughters differently. The last meta-analyses on the subject were conducted more than fifteen years ago, and changes in gender-specific child rearing in the past decade are quite plausible. In the current set of meta-analyses, based on 126 observational studies (15,034 families), we examined mothers' and fathers' differential use of autonomy-supportive and controlling strategies with boys and girls, and the role of moderators related to the decade in which the study was conducted, the observational context, and sample characteristics. Databases of Web of Science, ERIC, PsychInfo, Online Contents, Picarta, and Proquest were searched for studies examining differences in observed parental control of boys and girls between the ages of 0 and 18 years. Few differences were found in parents' use of control with boys and girls. Parents were slightly more controlling with boys than with girls, but the effect size was negligible (d = 0.08). The effect was larger, but still small, in normative groups and in samples with younger children. No overall effect for gender-differentiated autonomy-supportive strategies was found (d = 0.03). A significant effect of time emerged: studies published in the 1970s and 1980s reported more autonomy-supportive strategies with boys than toward girls, but from 1990 onwards parents showed somewhat more autonomy-supportive strategies with girls than toward boys. Taking into account parents' gender stereotypes might uncover subgroups of families where gender-differentiated control is salient, but based on our systematic review of the currently available large data base we conclude that in general the differences between parenting of boys versus girls are minimal.

[Inhibitory effects of Porphyromonas endodontalis lipopolysaccharides on proliferation and differentiation of mouse osteoblast].

PubMed

Li, Ren; Qiu, Li-hong; Yang, Di; Xue, Ming; Zhong, Ming

2011-03-01

To observe the effect of lipopolysaccharides (LPS) extracted from Porphyromonas endodontalis (Pe) on osteoblast cell proliferation and the activity of alkaline phosphatase (ALP) and interleukin (IL)-6 secretion and to investigate the role of Pe-LPS in osteoblast proliferation and differentiation. MC3T3-E1 cells were treated with different concentrations of Pe-LPS (10, 25, 50 mg/L) respectively. The relative growth rate (RGR) was detected by methyl thiazolyl tetrazolium (MTT) at different time point (12, 24, 48, 72 h). MC3T3-E1 cells were also stimulated with 10, 25 or 50 mg/L Pe-LPS for 6, 12, 24 and 48 h. The activity of ALP was detected by enzyme kinetics assay and the secretion of IL-6 was detected by enzyme-linked immunosorbent assay (ELISA). After the stimulation with 25 or 50 mg/L Pe-LPS for 72 h, the RGR of MC3T3-E1 cells descend to 87.46% and 71.12%. The ALP activities of MC3T3-E1 cells were inhibited obviously (P < 0.05) after the stimulation of different concentrations (10, 25, 50 mg/L) Pe-LPS for more than 24 hours. ELISA result showed that IL-6 increased to 32.21 ng/L treated with the 25 mg/L Pe-LPS for 6 h, 25 mg/L Pe-LPS gradually increased the expression of IL-6 from the ELISA results. Pe-LPS can induce the secretion of IL-6 in MC3T3-E1 and decrease the ALP activities of MC3T3-E1, the differentiation of osteoblasts was inhibited. with the long-time toxicity action of Pe-LPS, the proliferation rate of MC3T3-E1 also markedly decreased.

Differential activation of brain regions involved with error-feedback and imitation based motor simulation when observing self and an expert's actions in pilots and non-pilots on a complex glider landing task.

PubMed

Callan, Daniel E; Terzibas, Cengiz; Cassel, Daniel B; Callan, Akiko; Kawato, Mitsuo; Sato, Masa-Aki

2013-05-15

In this fMRI study we investigate neural processes related to the action observation network using a complex perceptual-motor task in pilots and non-pilots. The task involved landing a glider (using aileron, elevator, rudder, and dive brake) as close to a target as possible, passively observing a replay of one's own previous trial, passively observing a replay of an expert's trial, and a baseline do nothing condition. The objective of this study is to investigate two types of motor simulation processes used during observation of action: imitation based motor simulation and error-feedback based motor simulation. It has been proposed that the computational neurocircuitry of the cortex is well suited for unsupervised imitation based learning, whereas, the cerebellum is well suited for error-feedback based learning. Consistent with predictions, pilots (to a greater extent than non-pilots) showed significant differential activity when observing an expert landing the glider in brain regions involved with imitation based motor simulation (including premotor cortex PMC, inferior frontal gyrus IFG, anterior insula, parietal cortex, superior temporal gyrus, and middle temporal MT area) than when observing one's own previous trial which showed significant differential activity in the cerebellum (only for pilots) thought to be concerned with error-feedback based motor simulation. While there was some differential brain activity for pilots in regions involved with both Execution and Observation of the flying task (potential Mirror System sites including IFG, PMC, superior parietal lobule) the majority was adjacent to these areas (Observation Only Sites) (predominantly in PMC, IFG, and inferior parietal loblule). These regions showing greater activity for observation than for action may be involved with processes related to motor-based representational transforms that are not necessary when actually carrying out the task. Copyright © 2013 Elsevier Inc. All rights reserved.

Propylthiouracil, independent of its antithyroid effect, promotes vascular smooth muscle cells differentiation via PTEN induction.

PubMed

Chen, Wei-Jan; Pang, Jong-Hwei S; Lin, Kwang-Huei; Lee, Dany-Young; Hsu, Lung-An; Kuo, Chi-Tai

2010-01-01

Propylthiouracil (PTU), independent of its antithyroid effect, is recently found to have an antiatherosclerotic effect. The aim of this study is to determine the impact of PTU on phenotypic modulation of vascular smooth muscle cells (VSMCs), as phenotypic modulation may contribute to the growth of atherosclerotic lesions and neointimal formation after arterial injury. Propylthiouracil reduced neointimal formation in balloon-injured rat carotid arteries. In vitro, PTU may convert VSMCs from a serum-induced dedifferentiation state to a differentiated state, as indicated by a spindle-shaped morphology and an increase in the expression of SMC differentiation marker contractile proteins, including calponin and smooth muscle (SM)-myosin heavy chain (SM-MHC). Transient transfection studies in VSMCs demonstrated that PTU induced the activity of SMC marker genes (calponin and SM-MHC) promoters, indicating that PTU up-regulates these genes expression predominantly at the transcriptional level. Furthermore, PTU enhanced the expression of PTEN and inhibition of PTEN by siRNA knockdown blocked PTU-induced activation of contractile proteins expression and promoter activity. In the rat carotid injury model, PTU reversed the down-regulation of contractile proteins and up-regulated PTEN in the neointima induced by balloon injury. Propylthiouracil promotes VSMC differentiation, at lest in part, via induction of the PTEN-mediated pathway. These findings suggest a possible mechanism by which PTU may contribute to its beneficial effects on atherogenesis and neointimal formation after arterial injury.

Retinoic acid and nitric oxide promote cell proliferation and differentially induce neuronal differentiation in vitro in the cnidarian Renilla koellikeri.

PubMed

Estephane, Djoyce; Anctil, Michel

2010-10-01

Retinoic acid (RA) and nitric oxide (NO) are known to promote neuronal development in both vertebrates and invertebrates. Retinoic acid receptors appear to be present in cnidarians and NO plays various physiological roles in several cnidarians, but there is as yet no evidence that these agents have a role in neural development in this basal metazoan phylum. We used primary cultures of cells from the sea pansy Renilla koellikeri to investigate the involvement of these signaling molecules in cnidarian cell differentiation. We found that 9-cis RA induce cell proliferation in dose- and time-dependent manners in dishes coated with polylysine from the onset of culture. Cells in cultures exposed to RA in dishes devoid of polylysine were observed to differentiate into epithelium-associated cells, including sensory cells, without net gain in cell density. NO donors also induce cell proliferation in polylysine-coated dishes, but induce neuronal differentiation and neurite outgrowth in uncoated dishes. No other cell type undergoes differentiation in the presence of NO. These observations suggest that in the sea pansy (1) cell adhesion promotes proliferation without morphogenesis and this proliferation is modulated positively by 9-cis RA and NO, (2) 9-cis RA and NO differentially induce neuronal differentiation in nonadherent cells while repressing proliferation, and (3) the involvement of RA and NO in neuronal differentiation appeared early during the evolutionary emergence of nervous systems. 2010 Wiley Periodicals, Inc.

Variable Differential Reinforcement of Other Behavior (VDRO): Its Effectiveness as a Modification Procedure.

ERIC Educational Resources Information Center

Reuter, Katherine E.; LeBlanc, Judith M.

Two groups of five preschool children were trained to press a key for marbles for four sessions of variable ratio reinforcement (VR6). Subsequently, response decrement for the groups was compared during conditions of fixed and variable differential reinforcement of other behavior (DRO and VDRO). Fixed DRO was more effective for decreasing response…

The Role of Paracrine and Autocrine Signaling in the Early Phase of Adipogenic Differentiation of Adipose-derived Stem Cells

PubMed Central

Hemmingsen, Mette; Vedel, Søren; Skafte-Pedersen, Peder; Sabourin, David; Collas, Philippe; Bruus, Henrik; Dufva, Martin

2013-01-01

Introduction High cell density is known to enhance adipogenic differentiation of mesenchymal stem cells, suggesting secretion of signaling factors or cell-contact-mediated signaling. By employing microfluidic biochip technology, we have been able to separate these two processes and study the secretion pathways. Methods and results Adipogenic differentiation of human adipose-derived stem cells (ASCs) cultured in a microfluidic system was investigated under perfusion conditions with an adipogenic medium or an adipogenic medium supplemented with supernatant from differentiating ASCs (conditioned medium). Conditioned medium increased adipogenic differentiation compared to adipogenic medium with respect to accumulation of lipid-filled vacuoles and gene expression of key adipogenic markers (C/EBPα, C/EBPβ, C/EBPδ, PPARγ, LPL and adiponectin). The positive effects of conditioned medium were observed early in the differentiation process. Conclusions Using different cell densities and microfluidic perfusion cell cultures to suppress the effects of cell-released factors, we have demonstrated the significant role played by auto- or paracrine signaling in adipocyte differentiation. The cell-released factor(s) were shown to act in the recruitment phase of the differentiation process. PMID:23723991

TENOGENIC DIFFERENTIATION OF HUMAN MSCs INDUCED BY THE TOPOGRAPHY OF ELECTROCHEMICALLY ALIGNED COLLAGEN THREADS

PubMed Central

Kishore, Vipuil; Bullock, Whitney; Sun, Xuanhao; Van Dyke, William Scott; Akkus, Ozan

2011-01-01

Topographical cues from the extracellular microenvironment can influence cellular activity including proliferation and differentiation. Information on the effects of material topography on tenogenic differentiation of human mesenchymal stem cells (human MSCs) is limited. A methodology using the principles of isoelectric focusing has previously been developed in our laboratory to synthesize electrochemically aligned collagen (ELAC) threads that mimics the packing density, alignment and strength of collagen dense connective tissues. In the current study, human MSCs were cultured on ELAC and randomly-oriented collagen threads and the effect of collagen orientation on cell morphology, proliferation and tenogenic differentiation was investigated. The results indicate that higher rates of proliferation were observed on randomly oriented collagen threads compared to ELAC threads. On the other hand, tendon specific markers such as scleraxis, tenomodulin, tenascin-C and collagen-III were significantly increased on ELAC threads compared to randomly oriented collagen threads. Additionally, osteocalcin, a specific marker of bone differentiation was suppressed on ELAC threads. Previous studies have reported that BMP-12 is a key growth factor to induce tenogenic differentiation of human MSCs. To evaluate the synergistic effect of BMP-12 and collagen orientation, human MSCs were cultured on ELAC threads in culture medium supplemented with and without BMP-12. The results revealed that BMP-12 did not have an additional effect on the tenogenic differentiation of human MSCs on ELAC threads. Together, these results suggest that ELAC induces tenogenic differentiation of human MSCs by presenting an aligned and dense collagen substrate, akin to the tendon itself. In conclusion, ELAC has a significant potential to be used as a tendon replacement and in the development of an osteotendinous construct towards the regeneration of bone-tendon interfaces. PMID:22177622

The effects of differential negative reinforcement of other behavior and noncontingent escape on compliance.

PubMed

Kodak, Tiffany; Miltenberger, Raymond G; Romaniuk, Cathryn

2003-01-01

The present study evaluated the effects of noncontingent escape and differential negative reinforcement of other behavior in reducing problem behaviors and increasing compliance in 2 children with disabilities. Results showed that both methods reduced problem behavior and increased compliance for both children.

Relationship Between Integro-Differential Schrodinger Equation with a Symmetric Kernel and Position-Dependent Effective Mass

NASA Astrophysics Data System (ADS)

Khosropour, B.; Moayedi, S. K.; Sabzali, R.

2018-07-01

The solution of integro-differential Schrodinger equation (IDSE) which was introduced by physicists has a great role in the fields of science. The purpose of this paper comes in two parts. First, studying the relationship between integro-differential Schrodinger equation with a symmetric non-local potential and one-dimensional Schrodinger equation with a position-dependent effective mass. Second, we show that the quantum Hamiltonian for a particle with position-dependent mass after applying Liouville-Green transformations will be converted to a quantum Hamiltonian for a particle with constant mass.

Lifting the Differentiation Embargo.

PubMed

Latif, Anne-Louise; Holyoake, Tessa L

2016-09-22

Effective differentiation therapy for acute myeloid leukemia (AML) has been restricted to a small subset of patients with one defined genetic abnormality. Using an unbiased small molecule screen, Sykes et al. now identify a mechanism of de-repression of differentiation in several models of AML driven by distinct genetic drivers. Copyright © 2016 Elsevier Inc. All rights reserved.

Differential Effects of Camel Milk on Insulin Receptor Signaling – Toward Understanding the Insulin-Like Properties of Camel Milk

PubMed Central

Abdulrahman, Abdulrasheed O.; Ismael, Mohammad A.; Al-Hosaini, Khaled; Rame, Christelle; Al-Senaidy, Abdulrahman M.; Dupont, Joëlle; Ayoub, Mohammed Akli

2016-01-01

Previous studies on the Arabian camel (Camelus dromedarius) showed beneficial effects of its milk reported in diverse models of human diseases, including a substantial hypoglycemic activity. However, the cellular and molecular mechanisms involved in such effects remain completely unknown. In this study, we hypothesized that camel milk may act at the level of human insulin receptor (hIR) and its related intracellular signaling pathways. Therefore, we examined the effect of camel milk on the activation of hIR transiently expressed in human embryonic kidney 293 (HEK293) cells using bioluminescence resonance energy transfer (BRET) technology. BRET was used to assess, in live cells and real-time, the physical interaction between hIR and insulin receptor signaling proteins (IRS1) and the growth factor receptor-bound protein 2 (Grb2). Our data showed that camel milk did not promote any increase in the BRET signal between hIR and IRS1 or Grb2 in the absence of insulin stimulation. However, it significantly potentiated the maximal insulin-promoted BRET signal between hIR and Grb2 but not IRS1. Interestingly, camel milk appears to differentially impact the downstream signaling since it significantly activated ERK1/2 and potentiated the insulin-induced ERK1/2 but not Akt activation. These observations are to some extent consistent with the BRET data since ERK1/2 and Akt activation are known to reflect the engagement of Grb2 and IRS1 pathways, respectively. The preliminary fractionation of camel milk suggests the peptide/protein nature of the active component in camel milk. Together, our study demonstrates for the first time an allosteric effect of camel milk on insulin receptor conformation and activation with differential effects on its intracellular signaling. These findings should help to shed more light on the hypoglycemic activity of camel milk with potential therapeutic applications. PMID:26858689

Students' performance in accounting: differential effect of field dependence-independence as a learning style.

PubMed

Bernardi, Richard A

2003-08-01

This study examined the differential moderating effects associated with field dependence-independence and perceptions of stress on students' performance after controlling for SAT Mathematics and Verbal scores as well as students' actual effort on homework. The average performance of 178 third-year accounting majors over three examinations was used to evaluate their understanding of financial accounting. The students also took the Group Embedded Figures Test. While the data indicate that the most significant variables were students' effort, SAT Verbal scores, and their perceptions of stress, these variables were differentially associated with students' performance depending upon whether the student was classified as a field-independent or field-dependent learner.

Differential effect of ethanol and hydrogen peroxide on barrier function and prostaglandin E2 release in differentiated Caco-2 cells: selective prevention by growth factors.

PubMed

Catalioto, Rose-Marie; Festa, Carla; Triolo, Antonio; Altamura, Maria; Maggi, Carlo Alberto; Giuliani, Sandro

2009-02-01

The present study investigates the effects of ethanol and hydrogen peroxide (H(2)O(2)) on the barrier function and prostaglandin E(2) (PGE(2)) release in differentiated Caco-2 cells. Epithelial barrier integrity was estimated by measuring transepithelial electrical resistance (TEER), the transport of reference compounds and lactate dehydrogenase leakage, the PGE(2) release by enzyme immunoassay. Ethanol and H(2)O(2) decreased TEER and increased the transport of lucifer yellow without affecting that of propranolol and phenylalanine. Only the effects of ethanol were accompanied by PGE(2) production and were reversible without causing long-term cytotoxicity. The cyclooxygenase-2 inhibitor, NS-398, prevented the effect of ethanol on both PGE(2) release and TEER, while inhibition of both cyclooxygenase-2 and tyrosine kinase drastically compromised cell viability and TEER recovery. Hepatocyte growth factor, keratinocyte growth factor or insulin prevented the effect of ethanol on cell permeability, but not on PGE(2) release. Their combination prevented the effect of H(2)O(2). In conclusion, ethanol and H(2)O(2) increased paracellular permeability in differentiated Caco-2 cells without affecting transcellular and active transport. Cyclooxygenase-2 stimulated PGE(2) release mediated the reversible effect of ethanol on tight junctions and, meanwhile, contributed to cell survival. Growth factors, normally present in the intestine, exerted a selective protective effect toward paracellular permeability increase induced by irritants.

Progesterone receptor isoforms, agonists and antagonists differentially reprogram estrogen signaling

PubMed Central

Singhal, Hari; Greene, Marianne E.; Zarnke, Allison L.; Laine, Muriel; Al Abosy, Rose; Chang, Ya-Fang; Dembo, Anna G.; Schoenfelt, Kelly; Vadhi, Raga; Qiu, Xintao; Rao, Prakash; Santhamma, Bindu; Nair, Hareesh B.; Nickisch, Klaus J.; Long, Henry W.; Becker, Lev; Brown, Myles; Greene, Geoffrey L.

2018-01-01

Major roadblocks to developing effective progesterone receptor (PR)-targeted therapies in breast cancer include the lack of highly-specific PR modulators, a poor understanding of the pro- or anti-tumorigenic networks for PR isoforms and ligands, and an incomplete understanding of the cross talk between PR and estrogen receptor (ER) signaling. Through genomic analyses of xenografts treated with various clinically-relevant ER and PR-targeting drugs, we describe how the activation or inhibition of PR differentially reprograms estrogen signaling, resulting in the segregation of transcriptomes into separate PR agonist and antagonist-mediated groups. These findings address an ongoing controversy regarding the clinical utility of PR agonists and antagonists, alone or in combination with tamoxifen, for breast cancer management. Additionally, the two PR isoforms PRA and PRB, bind distinct but overlapping genomic sites and interact with different sets of co-regulators to differentially modulate estrogen signaling to be either pro- or anti-tumorigenic. Of the two isoforms, PRA inhibited gene expression and ER chromatin binding significantly more than PRB. Differential gene expression was observed in PRA and PRB-rich patient tumors and PRA-rich gene signatures had poorer survival outcomes. In support of antiprogestin responsiveness of PRA-rich tumors, gene signatures associated with PR antagonists, but not PR agonists, predicted better survival outcomes. The better patient survival associated with PR antagonists versus PR agonists treatments was further reflected in the higher in vivo anti-tumor activity of therapies that combine tamoxifen with PR antagonists and modulators. This study suggests that distinguishing common effects observed due to concomitant interaction of another receptor with its ligand (agonist or antagonist), from unique isoform and ligand-specific effects will inform the development of biomarkers for patient selection and translation of PR

An evaluation of two differential reinforcement procedures with escape extinction to treat food refusal.

PubMed

Patel, Meeta R; Piazza, Cathleen C; Martinez, Cheryl J; Volkert, Valerie M; Christine, M Santana

2002-01-01

Consumption of solids and liquids occurs as a chain of behaviors that may include accepting, swallowing, and retaining the food or drink. In the current investigation, we evaluated the relative effectiveness of differential reinforcement of the first behavior in the chain (acceptance) versus differential reinforcement for the terminal behavior in the chain (mouth clean). Three children who had been diagnosed with a feeding disorder participated. Acceptance remained at zero when differential reinforcement contingencies were implemented for acceptance or mouth clean. Acceptance and mouth clean increased for all 3 participants once escape extinction was added to the differential reinforcement procedures, independent of whether reinforcement was provided for acceptance or for mouth clean. Maintenance was observed in 2 children when escape extinction was removed from the treatment package. The mechanism by which consumption increased is discussed in relation to positive and negative reinforcement contingencies.

Human pancreatic islet-derived extracellular vesicles modulate insulin expression in 3D-differentiating iPSC clusters

PubMed Central

Andersson, Eva-Marie; Heath, Nikki; Persson-kry, Anette; Collins, Richard; Hicks, Ryan; Dekker, Niek; Forslöw, Anna

2017-01-01

It has been suggested that extracellular vesicles (EVs) can mediate crosstalk between hormones and metabolites within pancreatic tissue. However, the possible effect of pancreatic EVs on stem cell differentiation into pancreatic lineages remains unknown. Herein, human islet-derived EVs (h-Islet-EVs) were isolated, characterized and subsequently added to human induced pluripotent stem cell (iPSC) clusters during pancreatic differentiation. The h-islet-EVs had a mean size of 117±7 nm and showed positive expression of CD63 and CD81 EV markers as measured by ELISA. The presence of key pancreatic transcription factor mRNA, such as NGN3, MAFA and PDX1, and pancreatic hormone proteins such as C-peptide and glucagon, were confirmed in h-Islet-EVs. iPSC clusters were differentiated in suspension and at the end stages of the differentiation protocol, the mRNA expression of the main pancreatic transcription factors and pancreatic hormones was increased. H-Islet-EVs were supplemented to the iPSC clusters in the later stages of differentiation. It was observed that h-Islet-EVs were able to up-regulate the intracellular levels of C-peptide in iPSC clusters in a concentration-dependent manner. The effect of h-Islet-EVs on the differentiation of iPSC clusters cultured in 3D-collagen hydrogels was also assessed. Although increased mRNA expression for pancreatic markers was observed when culturing the iPSC clusters in 3D-collagen hydrogels, delivery of EVs did not affect the insulin or C-peptide intracellular content. Our results provide new information on the role of h-Islet-EVs in the regulation of insulin expression in differentiating iPSC clusters, and are highly relevant for pancreatic tissue engineering applications. PMID:29117231

Activin A Modulates CRIPTO-1/HNF4α+ Cells to Guide Cardiac Differentiation from Human Embryonic Stem Cells

PubMed Central

Duelen, Robin; Gilbert, Guillaume; Patel, Abdulsamie; de Schaetzen, Nathalie; De Waele, Liesbeth; Roderick, Llewelyn; Sipido, Karin R.; Verfaillie, Catherine M.; Buyse, Gunnar M.

2017-01-01

The use of human pluripotent stem cells in basic and translational cardiac research requires efficient differentiation protocols towards cardiomyocytes. In vitro differentiation yields heterogeneous populations of ventricular-, atrial-, and nodal-like cells hindering their potential applications in regenerative therapies. We described the effect of the growth factor Activin A during early human embryonic stem cell fate determination in cardiac differentiation. Addition of high levels of Activin A during embryoid body cardiac differentiation augmented the generation of endoderm derivatives, which in turn promoted cardiomyocyte differentiation. Moreover, a dose-dependent increase in the coreceptor expression of the TGF-β superfamily member CRIPTO-1 was observed in response to Activin A. We hypothesized that interactions between cells derived from meso- and endodermal lineages in embryoid bodies contributed to improved cell maturation in early stages of cardiac differentiation, improving the beating frequency and the percentage of contracting embryoid bodies. Activin A did not seem to affect the properties of cardiomyocytes at later stages of differentiation, measuring action potentials, and intracellular Ca2+ dynamics. These findings are relevant for improving our understanding on human heart development, and the proposed protocol could be further explored to obtain cardiomyocytes with functional phenotypes, similar to those observed in adult cardiac myocytes. PMID:28163723

A randomized trial of an early measles vaccine at 4½ months of age in Guinea-Bissau: sex-differential immunological effects.

PubMed

Jensen, Kristoffer Jarlov; Søndergaard, Mia; Andersen, Andreas; Sartono, Erliyani; Martins, Cesario; Garly, May-Lill; Eugen-Olsen, Jesper; Ullum, Henrik; Yazdanbakhsh, Maria; Aaby, Peter; Benn, Christine Stabell; Erikstrup, Christian

2014-01-01

After measles vaccine (MV), all-cause mortality is reduced more than can be explained by the prevention of measles, especially in females. We aimed to study the biological mechanisms underlying the observed non-specific and sex-differential effects of MV on mortality. Within a large randomised trial of MV at 4.5 months of age blood samples were obtained before and six weeks after randomisation to early MV or no early MV. We measured concentrations of cytokines and soluble receptors from plasma (interleukin-1 receptor agonist (IL-1Ra), IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, soluble urokinase-type plasminogen activator receptor), and secreted cytokines (interferon-γ, TNF-α, IL-5, IL-10, IL-13, IL-17) after in vitro challenge with innate agonists and recall antigens. We analysed the effect of MV in multiple imputation regression, overall and stratified by sex. The majority of the infants had previously been enrolled in a randomised trial of neonatal vitamin A. Post hoc we explored the potential effect modification by neonatal vitamin A. Overall, MV versus no MV was associated with higher plasma MCP-1 levels, but the effect was only significant among females. Additionally, MV was associated with increased plasma IL-1Ra. MV had significantly positive effects on plasma IL-1Ra and IL-8 levels in females, but not in males. These effects were strongest in vitamin A supplemented infants. Vitamin A shifted the effect of MV in a pro-inflammatory direction. In this explorative study we found indications of sex-differential effects of MV on several of the plasma biomarkers investigated; in particular MV increased levels in females, most strongly in vitamin A recipients. The findings support that sex and micronutrient supplementation should be taken into account when analysing vaccine effects. clinicaltrials.gov number NCT 00168545.

The Anti-Warburg Effect Elicited by the cAMP-PGC1α Pathway Drives Differentiation of Glioblastoma Cells into Astrocytes.

PubMed

Xing, Fan; Luan, Yizhao; Cai, Jing; Wu, Sihan; Mai, Jialuo; Gu, Jiayu; Zhang, Haipeng; Li, Kai; Lin, Yuan; Xiao, Xiao; Liang, Jiankai; Li, Yuan; Chen, Wenli; Tan, Yaqian; Sheng, Longxiang; Lu, Bingzheng; Lu, Wanjun; Gao, Mingshi; Qiu, Pengxin; Su, Xingwen; Yin, Wei; Hu, Jun; Chen, Zhongping; Sai, Ke; Wang, Jing; Chen, Furong; Chen, Yinsheng; Zhu, Shida; Liu, Dongbing; Cheng, Shiyuan; Xie, Zhi; Zhu, Wenbo; Yan, Guangmei

2017-01-10

Glioblastoma multiforme (GBM) is among the most aggressive of human cancers. Although differentiation therapy has been proposed as a potential approach to treat GBM, the mechanisms of induced differentiation remain poorly defined. Here, we established an induced differentiation model of GBM using cAMP activators that specifically directed GBM differentiation into astroglia. Transcriptomic and proteomic analyses revealed that oxidative phosphorylation and mitochondrial biogenesis are involved in induced differentiation of GBM. Dibutyryl cyclic AMP (dbcAMP) reverses the Warburg effect, as evidenced by increased oxygen consumption and reduced lactate production. Mitochondrial biogenesis induced by activation of the CREB-PGC1α pathway triggers metabolic shift and differentiation. Blocking mitochondrial biogenesis using mdivi1 or by silencing PGC1α abrogates differentiation; conversely, overexpression of PGC1α elicits differentiation. In GBM xenograft models and patient-derived GBM samples, cAMP activators also induce tumor growth inhibition and differentiation. Our data show that mitochondrial biogenesis and metabolic switch to oxidative phosphorylation drive the differentiation of tumor cells. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Differentiation Is an Expectation: A School Leader's Guide to Building a Culture of Differentiation

ERIC Educational Resources Information Center

Hewitt, Kimberly Kappler; Weckstein, Daniel K.

2011-01-01

Turn your school into a place where every child achieves. This book provides leaders with all that they need to promote differentiation in their schools and districts. Through research and first-hand experience, the authors have identified effective strategies for hiring differentiation-minded staff members, communicating the need for…

Observation of a superfluid Hall effect

PubMed Central

Jiménez-García, Karina; Williams, Ross A.; Beeler, Matthew C.; Perry, Abigail R.; Phillips, William D.; Spielman, Ian B.

2012-01-01

Measurement techniques based upon the Hall effect are invaluable tools in condensed-matter physics. When an electric current flows perpendicular to a magnetic field, a Hall voltage develops in the direction transverse to both the current and the field. In semiconductors, this behavior is routinely used to measure the density and charge of the current carriers (electrons in conduction bands or holes in valence bands)—internal properties of the system that are not accessible from measurements of the conventional resistance. For strongly interacting electron systems, whose behavior can be very different from the free electron gas, the Hall effect’s sensitivity to internal properties makes it a powerful tool; indeed, the quantum Hall effects are named after the tool by which they are most distinctly measured instead of the physics from which the phenomena originate. Here we report the first observation of a Hall effect in an ultracold gas of neutral atoms, revealed by measuring a Bose–Einstein condensate’s transport properties perpendicular to a synthetic magnetic field. Our observations in this vortex-free superfluid are in good agreement with hydrodynamic predictions, demonstrating that the system’s global irrotationality influences this superfluid Hall signal. PMID:22699494

Differential effects of tactile high- and low-frequency stimulation on tactile discrimination in human subjects.

PubMed

Ragert, Patrick; Kalisch, Tobias; Bliem, Barbara; Franzkowiak, Stephanie; Dinse, Hubert R

2008-01-23

Long-term potentiation (LTP) and long-term depression (LTD) play important roles in mediating activity-dependent changes in synaptic transmission and are believed to be crucial mechanisms underlying learning and cortical plasticity. In human subjects, however, the lack of adequate input stimuli for the induction of LTP and LTD makes it difficult to study directly the impact of such protocols on behavior. Using tactile high- and low-frequency stimulation protocols in humans, we explored the potential of such protocols for the induction of perceptual changes. We delivered tactile high-frequency and low-frequency stimuli (t-HFS, t-LFS) to skin sites of approximately 50 mm2 on the tip of the index finger. As assessed by 2-point discrimination, we demonstrate that 20 minutes of t-HFS improved tactile discrimination, while t-LFS impaired performance. T-HFS-effects were stable for at least 24 hours whereas t-LFS-induced changes recovered faster. While t-HFS changes were spatially very specific with no changes on the neighboring fingers, impaired tactile performance after t-LFS was also observed on the right middle-finger. A central finding was that for both t-LFS and t-HFS perceptual changes were dependent on the size of the stimulated skin area. No changes were observed when the stimulated area was very small (< 1 mm2) indicating special requirements for spatial summation. Our results demonstrate differential effects of such protocols in a frequency specific manner that might be related to LTP- and LTD-like changes in human subjects.

Annexin A1 Down-Regulation in Head and Neck Cancer Is Associated with Epithelial Differentiation Status

PubMed Central