A lysigenic programmed cell death-dependent process shapes schizogenously formed aerenchyma in the stems of the waterweed Egeria densa.

PubMed

Bartoli, G; Forino, L M C; Durante, M; Tagliasacchi, A M

2015-07-01

Plant adaptation to submergence can include the formation of prominent aerenchyma to facilitate gas exchange. The aim of this study was to characterize the differentiation of the constitutive aerenchyma in the stem of the aquatic macrophyte Egeria densa (Hydrocharitaceae) and to verify if any form of cell death might be involved. Plants were collected from a pool in a botanical garden. Aerenchyma differentiation and apoptotic hallmarks were investigated by light microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) assay coupled with genomic DNA extraction and gel electrophoresis (DNA laddering assay). Cell viability and the occurrence of peroxides and nitric oxide (NO) were determined histochemically using specific fluorogenic probes. Aerenchyma differentiation started from a hexagonally packed pre-aerenchymatic tissue and, following a basipetal and centripetal developmental pattern, produced a honeycomb arrangement. After an early schizogenous differentiation process, a late lysigenous programmed cell death- (PCD) dependent mechanism occurred. This was characterized by a number of typical apoptotic hallmarks, including DNA fragmentation, chromatin condensation, apoptotic-like bodies, partial cell wall lysis and plasmolysis. In addition, local increases in H2O2 and NO were observed and quantified. The differentiation of cortical aerenchyma in the stem of E. densa is a complex process, consisting of a combination of an early schizogenous differentiation mechanism and a late lysigenous PCD-dependent process. The PCD remodels the architecture of the gas spaces previously formed schizogenously, and also results in a reduction of O2-consuming cells and in recycling of material derived from the lysigenic dismantling of the cells. © The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Differentiating Instruction for Disabled Students in Inclusive Classrooms

ERIC Educational Resources Information Center

Broderick, Alicia; Mehta-Parekh, Heeral; Reid, D. Kim

2005-01-01

Differentiating instruction, a comprehensive approach to teaching, enables the successful inclusion of all students, including the disabled, in general-education classrooms. As inclusive educators, we argue that disability is an enacted, interactional process and not an empirical, stable fact or condition. We recommend planning responsive lessons…

Chemical aspects of the formation of the solar system

NASA Technical Reports Server (NTRS)

Arrhenius, G.

1978-01-01

Application of Alfven's theory for the formation of the solar system and the constraints imposed by the chemical composition of space materials are discussed with reference to chemical processes involved in the formation of the solar system. Evidence for the chemical properties of the space medium and the chemical consequences of the postulated physical differentiation processes are outlined, and interpretations based on structure and composition of meteorite material are indicated. A large range of topics, including processes involving chemical differentiation, temperature effects, and isotope fractionation, are examined.

Differentiating Co-Occurring Behavior Problems in Children with ADHD: Patterns of Emotional Reactivity and Executive Functioning

ERIC Educational Resources Information Center

Graziano, Paulo A.; McNamara, Joseph P.; Geffken, Gary R.; Reid, Adam M.

2013-01-01

Objective:This study examined whether "top-down" and "bottom-up" control processes can differentiate children with ADHD who exhibit co-occurring aggression and/or internalizing symptoms. Method: Participants included 74 children ("M" age = 10.7 years) with a "Diagnostic and Statistical…

The Promise of Differentiated Instruction for Enhancing the Mathematical Understandings of College Students

ERIC Educational Resources Information Center

Chamberlin, Michelle; Powers, Robert

2010-01-01

Mathematics instructors must respond to diverse needs of individual students, including different abilities, interests, learning styles and cultural backgrounds. To do so, grade kindergarten-12 teachers have been using differentiated instruction, a process of proactively modifying instruction based on students' needs. It is supported by literature…

Diapiric transfer of melt in Kilauea Iki lava lake, Hawaii: a quick, efficient process of igneous differentiation

USGS Publications Warehouse

Helz, R.T.; Kirschenbaum, H.; Marinenko, J.W.

1989-01-01

Kilauea Iki lava lake, formed in 1959, is a large pond of picritic basalt (average MgO content = 15.34% by weight), which has cooled and crystallized as a small, self-roofed magma chamber. Differentiation processes recognized as active in the lake include rather inefficient settling of the larger (2-10 mm) olivine phenocrysts, formation of segregation veins, and formation of diapir-like vertical olivine-rich bodies, all processes which occur in one or more of the other Kilauean lava lakes as well. In addition, most of the central part of Kilauea Iki has been affected by diapiric melt transfer. Diapiric melt transfer was active from 1960 to 1971 and has affected most of the central part of the lake from 13 m to at least 80 m. The process ran simultaneously with the other three main differentiation processes but started and stopped independently of the others. Calculations suggest that between 21 and 42 wt % liquid has been extracted from the depleted zone at 56-78 m in the center of the lake, making this a very efficient process of chemical differentiation. -from Authors

Mapping human pluripotent stem cell differentiation pathways using high throughput single-cell RNA-sequencing.

PubMed

Han, Xiaoping; Chen, Haide; Huang, Daosheng; Chen, Huidong; Fei, Lijiang; Cheng, Chen; Huang, He; Yuan, Guo-Cheng; Guo, Guoji

2018-04-05

Human pluripotent stem cells (hPSCs) provide powerful models for studying cellular differentiations and unlimited sources of cells for regenerative medicine. However, a comprehensive single-cell level differentiation roadmap for hPSCs has not been achieved. We use high throughput single-cell RNA-sequencing (scRNA-seq), based on optimized microfluidic circuits, to profile early differentiation lineages in the human embryoid body system. We present a cellular-state landscape for hPSC early differentiation that covers multiple cellular lineages, including neural, muscle, endothelial, stromal, liver, and epithelial cells. Through pseudotime analysis, we construct the developmental trajectories of these progenitor cells and reveal the gene expression dynamics in the process of cell differentiation. We further reprogram primed H9 cells into naïve-like H9 cells to study the cellular-state transition process. We find that genes related to hemogenic endothelium development are enriched in naïve-like H9. Functionally, naïve-like H9 show higher potency for differentiation into hematopoietic lineages than primed cells. Our single-cell analysis reveals the cellular-state landscape of hPSC early differentiation, offering new insights that can be harnessed for optimization of differentiation protocols.

Role of fibroblast growth factor receptors (FGFR) and FGFR like-1 (FGFRL1) in mesenchymal stromal cell differentiation to osteoblasts and adipocytes.

PubMed

Kähkönen, T E; Ivaska, K K; Jiang, M; Büki, K G; Väänänen, H K; Härkönen, P L

2018-02-05

Fibroblast growth factors (FGF) and their receptors (FGFRs) regulate many developmental processes including differentiation of mesenchymal stromal cells (MSC). We developed two MSC lines capable of differentiating to osteoblasts and adipocytes and studied the role of FGFRs in this process. We identified FGFR2 and fibroblast growth factor receptor like-1 (FGFRL1) as possible actors in MSC differentiation with gene microarray and qRT-PCR. FGFR2 and FGFRL1 mRNA expression strongly increased during MSC differentiation to osteoblasts. FGF2 treatment, resulting in downregulation of FGFR2, or silencing FGFR2 expression with siRNAs inhibited osteoblast differentiation. During adipocyte differentiation expression of FGFR1 and FGFRL1 increased and was down-regulated by FGF2. FGFR1 knockdown inhibited adipocyte differentiation. Silencing FGFR2 and FGFR1 in MSCs was associated with decreased FGFRL1 expression in osteoblasts and adipocytes, respectively. Our results suggest that FGFR1 and FGFR2 regulate FGFRL1 expression. FGFRL1 may mediate or modulate FGFR regulation of MSC differentiation together with FGFR2 in osteoblastic and FGFR1 in adipocytic lineage. Copyright © 2017 Elsevier B.V. All rights reserved.

Intestinal development and differentiation

PubMed Central

Noah, Taeko K.; Donahue, Bridgitte; Shroyer, Noah F.

2011-01-01

In this review, we present an overview of intestinal development and cellular differentiation of the intestinal epithelium. The review is separated into two sections: Section one summarizes organogenesis of the small and large intestines, including endoderm and gut tube formation in early embryogenesis, villus morphogenesis, and crypt formation. Section two reviews cell fate specification and differentiation of each cell type within the intestinal epithelium. Growth factor and transcriptional networks that regulate these developmental processes are summarized. PMID:21978911

SARTools: A DESeq2- and EdgeR-Based R Pipeline for Comprehensive Differential Analysis of RNA-Seq Data.

PubMed

Varet, Hugo; Brillet-Guéguen, Loraine; Coppée, Jean-Yves; Dillies, Marie-Agnès

2016-01-01

Several R packages exist for the detection of differentially expressed genes from RNA-Seq data. The analysis process includes three main steps, namely normalization, dispersion estimation and test for differential expression. Quality control steps along this process are recommended but not mandatory, and failing to check the characteristics of the dataset may lead to spurious results. In addition, normalization methods and statistical models are not exchangeable across the packages without adequate transformations the users are often not aware of. Thus, dedicated analysis pipelines are needed to include systematic quality control steps and prevent errors from misusing the proposed methods. SARTools is an R pipeline for differential analysis of RNA-Seq count data. It can handle designs involving two or more conditions of a single biological factor with or without a blocking factor (such as a batch effect or a sample pairing). It is based on DESeq2 and edgeR and is composed of an R package and two R script templates (for DESeq2 and edgeR respectively). Tuning a small number of parameters and executing one of the R scripts, users have access to the full results of the analysis, including lists of differentially expressed genes and a HTML report that (i) displays diagnostic plots for quality control and model hypotheses checking and (ii) keeps track of the whole analysis process, parameter values and versions of the R packages used. SARTools provides systematic quality controls of the dataset as well as diagnostic plots that help to tune the model parameters. It gives access to the main parameters of DESeq2 and edgeR and prevents untrained users from misusing some functionalities of both packages. By keeping track of all the parameters of the analysis process it fits the requirements of reproducible research.

Population genomics of the killer whale indicates ecotype evolution in sympatry involving both selection and drift.

PubMed

Moura, Andre E; Kenny, John G; Chaudhuri, Roy; Hughes, Margaret A; J Welch, Andreanna; Reisinger, Ryan R; de Bruyn, P J Nico; Dahlheim, Marilyn E; Hall, Neil; Hoelzel, A Rus

2014-11-01

The evolution of diversity in the marine ecosystem is poorly understood, given the relatively high potential for connectivity, especially for highly mobile species such as whales and dolphins. The killer whale (Orcinus orca) has a worldwide distribution, and individual social groups travel over a wide geographic range. Even so, regional populations have been shown to be genetically differentiated, including among different foraging specialists (ecotypes) in sympatry. Given the strong matrifocal social structure of this species together with strong resource specializations, understanding the process of differentiation will require an understanding of the relative importance of both genetic drift and local adaptation. Here we provide a high-resolution analysis based on nuclear single-nucleotide polymorphic markers and inference about differentiation at both neutral loci and those potentially under selection. We find that all population comparisons, within or among foraging ecotypes, show significant differentiation, including populations in parapatry and sympatry. Loci putatively under selection show a different pattern of structure compared to neutral loci and are associated with gene ontology terms reflecting physiologically relevant functions (e.g. related to digestion). The pattern of differentiation for one ecotype in the North Pacific suggests local adaptation and shows some fixed differences among sympatric ecotypes. We suggest that differential habitat use and resource specializations have promoted sufficient isolation to allow differential evolution at neutral and functional loci, but that the process is recent and dependent on both selection and drift. © 2014 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.

Population genomics of the killer whale indicates ecotype evolution in sympatry involving both selection and drift

PubMed Central

Moura, Andre E; Kenny, John G; Chaudhuri, Roy; Hughes, Margaret A; J Welch, Andreanna; Reisinger, Ryan R; de Bruyn, P J Nico; Dahlheim, Marilyn E; Hall, Neil; Hoelzel, A Rus

2014-01-01

The evolution of diversity in the marine ecosystem is poorly understood, given the relatively high potential for connectivity, especially for highly mobile species such as whales and dolphins. The killer whale (Orcinus orca) has a worldwide distribution, and individual social groups travel over a wide geographic range. Even so, regional populations have been shown to be genetically differentiated, including among different foraging specialists (ecotypes) in sympatry. Given the strong matrifocal social structure of this species together with strong resource specializations, understanding the process of differentiation will require an understanding of the relative importance of both genetic drift and local adaptation. Here we provide a high-resolution analysis based on nuclear single-nucleotide polymorphic markers and inference about differentiation at both neutral loci and those potentially under selection. We find that all population comparisons, within or among foraging ecotypes, show significant differentiation, including populations in parapatry and sympatry. Loci putatively under selection show a different pattern of structure compared to neutral loci and are associated with gene ontology terms reflecting physiologically relevant functions (e.g. related to digestion). The pattern of differentiation for one ecotype in the North Pacific suggests local adaptation and shows some fixed differences among sympatric ecotypes. We suggest that differential habitat use and resource specializations have promoted sufficient isolation to allow differential evolution at neutral and functional loci, but that the process is recent and dependent on both selection and drift. PMID:25244680

Ethylene-induced differential gene expression during abscission of citrus leaves

PubMed Central

Merelo, Paz; Cercós, Manuel; Tadeo, Francisco R.; Talón, Manuel

2008-01-01

The main objective of this work was to identify and classify genes involved in the process of leaf abscission in Clementina de Nules (Citrus clementina Hort. Ex Tan.). A 7 K unigene citrus cDNA microarray containing 12 K spots was used to characterize the transcriptome of the ethylene-induced abscission process in laminar abscission zone-enriched tissues and the petiole of debladed leaf explants. In these conditions, ethylene induced 100% leaf explant abscission in 72 h while, in air-treated samples, the abscission period started later and took 240 h. Gene expression monitored during the first 36 h of ethylene treatment showed that out of the 12 672 cDNA microarray probes, ethylene differentially induced 725 probes distributed as follows: 216 (29.8%) probes in the laminar abscission zone and 509 (70.2%) in the petiole. Functional MIPS classification and manual annotation of differentially expressed genes highlighted key processes regulating the activation and progress of the cell separation that brings about abscission. These included cell-wall modification, lipid transport, protein biosynthesis and degradation, and differential activation of signal transduction and transcription control pathways. Expression data associated with the petiole indicated the occurrence of a double defensive strategy mediated by the activation of a biochemical programme including scavenging ROS, defence and PR genes, and a physical response mostly based on lignin biosynthesis and deposition. This work identifies new genes probably involved in the onset and development of the leaf abscission process and suggests a different but co-ordinated and complementary role for the laminar abscission zone and the petiole during the process of abscission. PMID:18515267

Shyness and Emotion-Processing Skills in Preschoolers: A 6-Month Longitudinal Study

ERIC Educational Resources Information Center

Strand, Paul S.; Cerna, Sandra; Downs, Andrew

2008-01-01

The present study utilized a short-term longitudinal research design to examine the hypothesis that shyness in preschoolers is differentially related to different aspects of emotion processing. Using teacher reports of shyness and performance measures of emotion processing, including (1) facial emotion recognition, (2) non-facial emotion…

Analysis of transcripts differentially expressed between fruited and deflowered 'Gala' adult trees: a contribution to biennial bearing understanding in apple.

PubMed

Guitton, B; Kelner, J J; Celton, J M; Sabau, X; Renou, J P; Chagné, D; Costes, E

2016-02-29

The transition from vegetative to floral state in shoot apical meristems (SAM) is a key event in plant development and is of crucial importance for reproductive success. In perennial plants, this event is recurrent during tree life and subject to both within-tree and between-years heterogeneity. In the present study, our goal was to identify candidate processes involved in the repression or induction of flowering in apical buds of adult apple trees. Genes differentially expressed (GDE) were examined between trees artificially set in either 'ON' or 'OFF' situation, and in which floral induction (FI) was shown to be inhibited or induced in most buds, respectively, using qRT-PCR and microarray analysis. From the period of FI through to flower differentiation, GDE belonged to four main biological processes (i) response to stimuli, including response to oxidative stress; (ii) cellular processes, (iii) cell wall biogenesis, and (iv) metabolic processes including carbohydrate biosynthesis and lipid metabolic process. Several key regulator genes, especially TEMPRANILLO (TEM), FLORAL TRANSITION AT MERISTEM (FTM1) and SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) were found differentially expressed. Moreover, homologs of SPL and Leucine-Rich Repeat proteins were present under QTL zones previously detected for biennial bearing. This data set suggests that apical buds of 'ON' and 'OFF' trees were in different physiological states, resulting from different metabolic, hormonal and redox status which are likely to contribute to FI control in adult apple trees. Investigations on carbohydrate and hormonal fluxes from sources to SAM and on cell detoxification process are expected to further contribute to the identification of the underlying physiological mechanisms of FI in adult apple trees.

Extracellular Matrix Degradation and Remodeling in Development and Disease

PubMed Central

Lu, Pengfei; Takai, Ken; Weaver, Valerie M.; Werb, Zena

2011-01-01

The extracellular matrix (ECM) serves diverse functions and is a major component of the cellular microenvironment. The ECM is a highly dynamic structure, constantly undergoing a remodeling process where ECM components are deposited, degraded, or otherwise modified. ECM dynamics are indispensible during restructuring of tissue architecture. ECM remodeling is an important mechanism whereby cell differentiation can be regulated, including processes such as the establishment and maintenance of stem cell niches, branching morphogenesis, angiogenesis, bone remodeling, and wound repair. In contrast, abnormal ECM dynamics lead to deregulated cell proliferation and invasion, failure of cell death, and loss of cell differentiation, resulting in congenital defects and pathological processes including tissue fibrosis and cancer. Understanding the mechanisms of ECM remodeling and its regulation, therefore, is essential for developing new therapeutic interventions for diseases and novel strategies for tissue engineering and regenerative medicine. PMID:21917992

Differential invasion success of salmonids in southern Chile: patterns and hypotheses

Treesearch

Ivan Arismendi; Brooke E. Penaluna; Jason B. Dunham; Carlos Garcia de Leaniz; Doris Soto; Ian A. Fleming; Daniel Gomez-Uchida; Gonzalo Gajardo; Pamela V. Varga; Jorge León-Muñoz

2014-01-01

Biological invasions create complex ecological and societal issues worldwide. Most of the knowledge about invasions comes only from successful invaders, but less is known about which processes determine the differential success of invasions. In this review, we develop a framework to identify the main dimensions driving the success and failure of invaders, including...

Identification and Characterization of FGF2-Dependent mRNA: microRNA Networks During Lens Fiber Cell Differentiation

PubMed Central

Wolf, Louise; Gao, Chun S.; Gueta, Karen; Xie, Qing; Chevallier, Tiphaine; Podduturi, Nikhil R.; Sun, Jian; Conte, Ivan; Zelenka, Peggy S.; Ashery-Padan, Ruth; Zavadil, Jiri; Cvekl, Ales

2013-01-01

MicroRNAs (miRNAs) and fibroblast growth factor (FGF) signaling regulate a wide range of cellular functions, including cell specification, proliferation, migration, differentiation, and survival. In lens, both these systems control lens fiber cell differentiation; however, a possible link between these processes remains to be examined. Herein, the functional requirement for miRNAs in differentiating lens fiber cells was demonstrated via conditional inactivation of Dicer1 in mouse (Mus musculus) lens. To dissect the miRNA-dependent pathways during lens differentiation, we used a rat (Rattus norvegicus) lens epithelial explant system, induced by FGF2 to differentiate, followed by mRNA and miRNA expression profiling. Transcriptome and miRNome analysis identified extensive FGF2-regulated cellular responses that were both independent and dependent on miRNAs. We identified 131 FGF2-regulated miRNAs. Seventy-six of these miRNAs had at least two in silico predicted and inversely regulated target mRNAs. Genes modulated by the greatest number of FGF-regulated miRNAs include DNA-binding transcription factors Nfib, Nfat5/OREBP, c-Maf, Ets1, and N-Myc. Activated FGF signaling influenced bone morphogenetic factor/transforming growth factor-β, Notch, and Wnt signaling cascades implicated earlier in lens differentiation. Specific miRNA:mRNA interaction networks were predicted for c-Maf, N-Myc, and Nfib (DNA-binding transcription factors); Cnot6, Cpsf6, Dicer1, and Tnrc6b (RNA to miRNA processing); and Ash1l, Med1/PBP, and Kdm5b/Jarid1b/Plu1 (chromatin remodeling). Three miRNAs, including miR-143, miR-155, and miR-301a, down-regulated expression of c-Maf in the 3′-UTR luciferase reporter assays. These present studies demonstrate for the first time global impact of activated FGF signaling in lens cell culture system and predicted novel gene regulatory networks connected by multiple miRNAs that regulate lens differentiation. PMID:24142921

Chromatin in embryonic stem cell neuronal differentiation.

PubMed

Meshorer, E

2007-03-01

Chromatin, the basic regulatory unit of the eukaryotic genetic material, is controlled by epigenetic mechanisms including histone modifications, histone variants, DNA methylation and chromatin remodeling. Cellular differentiation involves large changes in gene expression concomitant with alterations in genome organization and chromatin structure. Such changes are particularly evident in self-renewing pluripotent embryonic stem cells, which begin, in terms of cell fate, as a tabula rasa, and through the process of differentiation, acquire distinct identities. Here I describe the changes in chromatin that accompany neuronal differentiation, particularly of embryonic stem cells, and discuss how chromatin serves as the master regulator of cellular destiny.

Data-Mining-Based Intelligent Differential Relaying for Transmission Lines Including UPFC and Wind Farms.

PubMed

Jena, Manas Kumar; Samantaray, Subhransu Ranjan

2016-01-01

This paper presents a data-mining-based intelligent differential relaying scheme for transmission lines, including flexible ac transmission system device, such as unified power flow controller (UPFC) and wind farms. Initially, the current and voltage signals are processed through extended Kalman filter phasor measurement unit for phasor estimation, and 21 potential features are computed at both ends of the line. Once the features are extracted at both ends, the corresponding differential features are derived. These differential features are fed to a data-mining model known as decision tree (DT) to provide the final relaying decision. The proposed technique has been extensively tested for single-circuit transmission line, including UPFC and wind farms with in-feed, double-circuit line with UPFC on one line and wind farm as one of the substations with wide variations in operating parameters. The test results obtained from simulation as well as in real-time digital simulator testing indicate that the DT-based intelligent differential relaying scheme is highly reliable and accurate with a response time of 2.25 cycles from the fault inception.

Retinoic acid-induced differentiation increases the rate of oxygen consumption and enhances the spare respiratory capacity of mitochondria in SH-SY5Y cells.

PubMed

Xun, Zhiyin; Lee, Do-Yup; Lim, James; Canaria, Christie A; Barnebey, Adam; Yanonne, Steven M; McMurray, Cynthia T

2012-04-01

Retinoic acid (RA) is used in differentiation therapy to treat a variety of cancers including neuroblastoma. The contributing factors for its therapeutic efficacy are poorly understood. However, mitochondria (MT) have been implicated as key effectors in RA-mediated differentiation process. Here we utilize the SH-SY5Y human neuroblastoma cell line as a model to examine how RA influences MT during the differentiation process. We find that RA confers an approximately sixfold increase in the oxygen consumption rate while the rate of glycolysis modestly increases. RA treatment does not increase the number of MT or cause measurable changes in the composition of the electron transport chain. Rather, RA treatment significantly increases the mitochondrial spare respiratory capacity. We propose a competition model for the therapeutic effects of RA. Specifically, the high metabolic rate in differentiated cells limits the availability of metabolic nutrients for use by the undifferentiated cells and suppresses their growth. Thus, RA treatment provides a selective advantage for the differentiated state. Published by Elsevier Ireland Ltd.

Retinoic acid-induced differentiation increases the rate of oxygen consumption and enhances the spare respiratory capacity of mitochondria in SH-SY5Y cells

PubMed Central

Xun, Zhiyin; Lee, Do-Yup; Lim, James; Canaria, Christie A.; Barnebey, Adam; Yanonne, Steven M.; McMurray, Cynthia T.

2012-01-01

Retinoic acid (RA) is used in differentiation therapy to treat a variety of cancers including neuroblastoma. The contributing factors for its therapeutic efficacy are poorly understood. However, mitochondria (MT) have been implicated as key effectors in RA-mediated differentiation process. Here we utilize the SH-SY5Y human neuroblastoma cell line as a model to examine how RA influences MT during the differentiation process. We find that RA confers an approximately 6-fold increase in the oxygen consumption rate while the rate of glycolysis modestly increases. RA treatment does not increase the number of MT or cause measurable changes in the composition of the electron transport chain. Rather, RA treatment significantly increases the mitochondrial spare respiratory capacity. We propose a competition model for the therapeutic effects of RA. Specifically, the high metabolic rate in differentiated cells limits the availability of metabolic nutrients for use by the undifferentiated cells and suppresses their growth. Thus, RA treatment provides a selective advantage for the differentiated state. PMID:22336883

Fingerprint image enhancement by differential hysteresis processing.

PubMed

Blotta, Eduardo; Moler, Emilce

2004-05-10

A new method to enhance defective fingerprints images through image digital processing tools is presented in this work. When the fingerprints have been taken without any care, blurred and in some cases mostly illegible, as in the case presented here, their classification and comparison becomes nearly impossible. A combination of spatial domain filters, including a technique called differential hysteresis processing (DHP), is applied to improve these kind of images. This set of filtering methods proved to be satisfactory in a wide range of cases by uncovering hidden details that helped to identify persons. Dactyloscopy experts from Policia Federal Argentina and the EAAF have validated these results.

A Comparative Analysis of Industrial Escherichia coli K–12 and B Strains in High-Glucose Batch Cultivations on Process-, Transcriptome- and Proteome Level

PubMed Central

Marisch, Karoline; Bayer, Karl; Scharl, Theresa; Mairhofer, Juergen; Krempl, Peter M.; Hummel, Karin; Razzazi-Fazeli, Ebrahim; Striedner, Gerald

2013-01-01

Escherichia coli K–12 and B strains are among the most frequently used bacterial hosts for production of recombinant proteins on an industrial scale. To improve existing processes and to accelerate bioprocess development, we performed a detailed host analysis. We investigated the different behaviors of the E. coli production strains BL21, RV308, and HMS174 in response to high-glucose concentrations. Tightly controlled cultivations were conducted under defined environmental conditions for the in-depth analysis of physiological behavior. In addition to acquisition of standard process parameters, we also used DNA microarray analysis and differential gel electrophoresis (EttanTM DIGE). Batch cultivations showed different yields of the distinct strains for cell dry mass and growth rate, which were highest for BL21. In addition, production of acetate, triggered by excess glucose supply, was much higher for the K–12 strains compared to the B strain. Analysis of transcriptome data showed significant alteration in 347 of 3882 genes common among all three hosts. These differentially expressed genes included, for example, those involved in transport, iron acquisition, and motility. The investigation of proteome patterns additionally revealed a high number of differentially expressed proteins among the investigated hosts. The subsequently selected 38 spots included proteins involved in transport and motility. The results of this comprehensive analysis delivered a full genomic picture of the three investigated strains. Differentially expressed groups for targeted host modification were identified like glucose transport or iron acquisition, enabling potential optimization of strains to improve yield and process quality. Dissimilar growth profiles of the strains confirm different genotypes. Furthermore, distinct transcriptome patterns support differential regulation at the genome level. The identified proteins showed high agreement with the transcriptome data and suggest similar regulation within a host at both levels for the identified groups. Such host attributes need to be considered in future process design and operation. PMID:23950949

A comparative analysis of industrial Escherichia coli K-12 and B strains in high-glucose batch cultivations on process-, transcriptome- and proteome level.

PubMed

Marisch, Karoline; Bayer, Karl; Scharl, Theresa; Mairhofer, Juergen; Krempl, Peter M; Hummel, Karin; Razzazi-Fazeli, Ebrahim; Striedner, Gerald

2013-01-01

Escherichia coli K-12 and B strains are among the most frequently used bacterial hosts for production of recombinant proteins on an industrial scale. To improve existing processes and to accelerate bioprocess development, we performed a detailed host analysis. We investigated the different behaviors of the E. coli production strains BL21, RV308, and HMS174 in response to high-glucose concentrations. Tightly controlled cultivations were conducted under defined environmental conditions for the in-depth analysis of physiological behavior. In addition to acquisition of standard process parameters, we also used DNA microarray analysis and differential gel electrophoresis (Ettan(TM) DIGE). Batch cultivations showed different yields of the distinct strains for cell dry mass and growth rate, which were highest for BL21. In addition, production of acetate, triggered by excess glucose supply, was much higher for the K-12 strains compared to the B strain. Analysis of transcriptome data showed significant alteration in 347 of 3882 genes common among all three hosts. These differentially expressed genes included, for example, those involved in transport, iron acquisition, and motility. The investigation of proteome patterns additionally revealed a high number of differentially expressed proteins among the investigated hosts. The subsequently selected 38 spots included proteins involved in transport and motility. The results of this comprehensive analysis delivered a full genomic picture of the three investigated strains. Differentially expressed groups for targeted host modification were identified like glucose transport or iron acquisition, enabling potential optimization of strains to improve yield and process quality. Dissimilar growth profiles of the strains confirm different genotypes. Furthermore, distinct transcriptome patterns support differential regulation at the genome level. The identified proteins showed high agreement with the transcriptome data and suggest similar regulation within a host at both levels for the identified groups. Such host attributes need to be considered in future process design and operation.

Metabolic phenotyping of a model of adipocyte differentiation

PubMed Central

Roberts, Lee D.; Virtue, Sam; Vidal-Puig, Antonio; Nicholls, Andrew W.

2009-01-01

The 3T3-L1 murine cell line is a robust and widely used model for the study of adipogenesis and processes occurring in mature adipocytes. The fibroblastic like cells can be induced by hormones to differentiate into mature adipocytes. In this study, the metabolic phenotype associated with differentiation of the 3T3-L1 cell line has been studied using gas chromatography-mass spectrometry, 1H nuclear magnetic resonance spectroscopy, liquid chromatography-mass spectrometry, direct infusion-mass spectrometry, and 13C substrate labeling in conjunction with multivariate statistics. The changes in metabolite concentrations at distinct periods during differentiation have been defined including alterations in the TCA cycle, glycolysis, the production of odd chain fatty acids by α-oxidation, fatty acid synthesis, fatty acid desaturation, polyamine biosynthesis, and trans-esterification to produce complex lipids. The metabolic changes induced during differentiation of the 3T3-L1 cell line were then compared with the metabolic differences between pre- and postdifferentiation primary adipocytes. These metabolic alterations reflect the changing role of the 3T3-L1 cells during differentiation, as well as possibly providing metabolic triggers to stimulate the processes which occur during differentiation. PMID:19602617

Ultrasonographic Differentiation of Lateral Elbow Pain

PubMed Central

Obuchowicz, R.; Bonczar, M.

2016-01-01

Lateral elbow pain is often attributed to degenerative or posttraumatic impairment of the common extensor tendon. Ultrasonography assesses the soft tissue structures of the lateral elbow, allowing the differentiation between various underlying processes, including angiofibroblastic degeneration, hyaline degeneration, and inflammation, and exclusion of other possible causes of pain such as posterior interosseous and lateral antebrachial nerve compression. Furthermore, the real-time imaging nature of ultrasonography enables the detection of impingement of the lateral synovial fold, degenerative changes in the elbow recess, and elbow posterolateral instability during dynamic maneuvers. Ultrasonography is widely accessible and well tolerated by patients, making it a perfect method for establishing an initial diagnosis and monitoring the healing process. This review describes the possible causes of lateral elbow pain and their ultrasonographic differentiation. PMID:27689169

Integrated Transcriptomic and Epigenomic Analysis of Primary Human Lung Epithelial Cell Differentiation

PubMed Central

Marconett, Crystal N.; Zhou, Beiyun; Rieger, Megan E.; Selamat, Suhaida A.; Dubourd, Mickael; Fang, Xiaohui; Lynch, Sean K.; Stueve, Theresa Ryan; Siegmund, Kimberly D.; Berman, Benjamin P.

2013-01-01

Elucidation of the epigenetic basis for cell-type specific gene regulation is key to gaining a full understanding of how the distinct phenotypes of differentiated cells are achieved and maintained. Here we examined how epigenetic changes are integrated with transcriptional activation to determine cell phenotype during differentiation. We performed epigenomic profiling in conjunction with transcriptomic profiling using in vitro differentiation of human primary alveolar epithelial cells (AEC). This model recapitulates an in vivo process in which AEC transition from one differentiated cell type to another during regeneration following lung injury. Interrogation of histone marks over time revealed enrichment of specific transcription factor binding motifs within regions of changing chromatin structure. Cross-referencing of these motifs with pathways showing transcriptional changes revealed known regulatory pathways of distal alveolar differentiation, such as the WNT and transforming growth factor beta (TGFB) pathways, and putative novel regulators of adult AEC differentiation including hepatocyte nuclear factor 4 alpha (HNF4A), and the retinoid X receptor (RXR) signaling pathways. Inhibition of the RXR pathway confirmed its functional relevance for alveolar differentiation. Our incorporation of epigenetic data allowed specific identification of transcription factors that are potential direct upstream regulators of the differentiation process, demonstrating the power of this approach. Integration of epigenomic data with transcriptomic profiling has broad application for the identification of regulatory pathways in other models of differentiation. PMID:23818859

Estrogens and development

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

McLachlan, J.A.; Newbold, R.R.

1987-11-01

The normal development of the genital organs of mammals, including humans, is under hormonal control. A role for the female sex hormone estrogen in this process is still unclear. However, exposure of experimental animals or humans to the potent exogenous estrogen, diethylstilbestrol (DES), results in persistent differentiation effects. Since many chemicals in the environment are weakly estrogenic, the possibility of hormonally altered differentiation must be considered.

Color separation in forensic image processing using interactive differential evolution.

PubMed

Mushtaq, Harris; Rahnamayan, Shahryar; Siddiqi, Areeb

2015-01-01

Color separation is an image processing technique that has often been used in forensic applications to differentiate among variant colors and to remove unwanted image interference. This process can reveal important information such as covered text or fingerprints in forensic investigation procedures. However, several limitations prevent users from selecting the appropriate parameters pertaining to the desired and undesired colors. This study proposes the hybridization of an interactive differential evolution (IDE) and a color separation technique that no longer requires users to guess required control parameters. The IDE algorithm optimizes these parameters in an interactive manner by utilizing human visual judgment to uncover desired objects. A comprehensive experimental verification has been conducted on various sample test images, including heavily obscured texts, texts with subtle color variations, and fingerprint smudges. The advantage of IDE is apparent as it effectively optimizes the color separation parameters at a level indiscernible to the naked eyes. © 2014 American Academy of Forensic Sciences.

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

Transcriptomic Profiling Discloses Molecular and Cellular Events Related to Neuronal Differentiation in SH-SY5Y Neuroblastoma Cells.

PubMed

Pezzini, Francesco; Bettinetti, Laura; Di Leva, Francesca; Bianchi, Marzia; Zoratti, Elisa; Carrozzo, Rosalba; Santorelli, Filippo M; Delledonne, Massimo; Lalowski, Maciej; Simonati, Alessandro

2017-05-01

Human SH-SY5Y neuroblastoma cells are widely utilized in in vitro studies to dissect out pathogenetic mechanisms of neurodegenerative disorders. These cells are considered as neuronal precursors and differentiate into more mature neuronal phenotypes under selected growth conditions. In this study, in order to decipher the pathways and cellular processes underlying neuroblastoma cell differentiation in vitro, we performed systematic transcriptomic (RNA-seq) and bioinformatic analysis of SH-SY5Y cells differentiated according to a two-step paradigm: retinoic acid treatment followed by enriched neurobasal medium. Categorization of 1989 differentially expressed genes (DEGs) identified in differentiated cells functionally linked them to changes in cell morphology including remodelling of plasma membrane and cytoskeleton, and neuritogenesis. Seventy-three DEGs were assigned to axonal guidance signalling pathway, and the expression of selected gene products such as neurotrophin receptors, the functionally related SLITRK6, and semaphorins, was validated by immunoblotting. Along with these findings, the differentiated cells exhibited an ability to elongate longer axonal process as assessed by the neuronal cytoskeletal markers biochemical characterization and morphometric evaluation. Recognition of molecular events occurring in differentiated SH-SY5Y cells is critical to accurately interpret the cellular responses to specific stimuli in studies on disease pathogenesis.

Teaching Simulation and Modelling at Royal Military College.

ERIC Educational Resources Information Center

Bonin, Hugues W.; Weir, Ronald D.

1984-01-01

Describes a course designed to assist students in writing differential equations to represent chemical processes and to solve these problems on digital computers. Course outline and discussion of computer projects and the simulation and optimization of a continuously stirred tank reactor process are included. (JN)

Jitter model and signal processing techniques for pulse width modulation optical recording

NASA Technical Reports Server (NTRS)

Liu, Max M.-K.

1991-01-01

A jitter model and signal processing techniques are discussed for data recovery in Pulse Width Modulation (PWM) optical recording. In PWM, information is stored through modulating sizes of sequential marks alternating in magnetic polarization or in material structure. Jitter, defined as the deviation from the original mark size in the time domain, will result in error detection if it is excessively large. A new approach is taken in data recovery by first using a high speed counter clock to convert time marks to amplitude marks, and signal processing techniques are used to minimize jitter according to the jitter model. The signal processing techniques include motor speed and intersymbol interference equalization, differential and additive detection, and differential and additive modulation.

Retrospective estimation of breeding phenology of American Goldfinch (Carduelis tristis) using pattern oriented modeling

EPA Science Inventory

Avian seasonal productivity is often modeled as a time-limited stochastic process. Many mathematical formulations have been proposed, including individual based models, continuous-time differential equations, and discrete Markov models. All such models typically include paramete...

SCOUP: a probabilistic model based on the Ornstein-Uhlenbeck process to analyze single-cell expression data during differentiation.

PubMed

Matsumoto, Hirotaka; Kiryu, Hisanori

2016-06-08

Single-cell technologies make it possible to quantify the comprehensive states of individual cells, and have the power to shed light on cellular differentiation in particular. Although several methods have been developed to fully analyze the single-cell expression data, there is still room for improvement in the analysis of differentiation. In this paper, we propose a novel method SCOUP to elucidate differentiation process. Unlike previous dimension reduction-based approaches, SCOUP describes the dynamics of gene expression throughout differentiation directly, including the degree of differentiation of a cell (in pseudo-time) and cell fate. SCOUP is superior to previous methods with respect to pseudo-time estimation, especially for single-cell RNA-seq. SCOUP also successfully estimates cell lineage more accurately than previous method, especially for cells at an early stage of bifurcation. In addition, SCOUP can be applied to various downstream analyses. As an example, we propose a novel correlation calculation method for elucidating regulatory relationships among genes. We apply this method to a single-cell RNA-seq data and detect a candidate of key regulator for differentiation and clusters in a correlation network which are not detected with conventional correlation analysis. We develop a stochastic process-based method SCOUP to analyze single-cell expression data throughout differentiation. SCOUP can estimate pseudo-time and cell lineage more accurately than previous methods. We also propose a novel correlation calculation method based on SCOUP. SCOUP is a promising approach for further single-cell analysis and available at https://github.com/hmatsu1226/SCOUP.

The Practice of Information Processing Model in the Teaching of Cognitive Strategies

ERIC Educational Resources Information Center

Ozel, Ali

2009-01-01

In this research, the differentiation condition of teaching the learning strategies depending on the time which the first grade of primary school teachers carried out to form an information-process skeleton on student is tried to be found out. This process including the efforts of 260 teachers in this direction consists of whether the adequate…

Enhanced expression of FNDC5 in human embryonic stem cell-derived neural cells along with relevant embryonic neural tissues.

PubMed

Ghahrizjani, Fatemeh Ahmadi; Ghaedi, Kamran; Salamian, Ahmad; Tanhaei, Somayeh; Nejati, Alireza Shoaraye; Salehi, Hossein; Nabiuni, Mohammad; Baharvand, Hossein; Nasr-Esfahani, Mohammad Hossein

2015-02-25

Availability of human embryonic stem cells (hESCs) has enhanced the capability of basic and clinical research in the context of human neural differentiation. Derivation of neural progenitor (NP) cells from hESCs facilitates the process of human embryonic development through the generation of neuronal subtypes. We have recently indicated that fibronectin type III domain containing 5 protein (FNDC5) expression is required for appropriate neural differentiation of mouse embryonic stem cells (mESCs). Bioinformatics analyses have shown the presence of three isoforms for human FNDC5 mRNA. To differentiate which isoform of FNDC5 is involved in the process of human neural differentiation, we have used hESCs as an in vitro model for neural differentiation by retinoic acid (RA) induction. The hESC line, Royan H5, was differentiated into a neural lineage in defined adherent culture treated by RA and basic fibroblast growth factor (bFGF). We collected all cell types that included hESCs, rosette structures, and neural cells in an attempt to assess the expression of FNDC5 isoforms. There was a contiguous increase in all three FNDC5 isoforms during the neural differentiation process. Furthermore, the highest level of expression of the isoforms was significantly observed in neural cells compared to hESCs and the rosette structures known as neural precursor cells (NPCs). High expression levels of FNDC5 in human fetal brain and spinal cord tissues have suggested the involvement of this gene in neural tube development. Additional research is necessary to determine the major function of FDNC5 in this process. Copyright © 2014 Elsevier B.V. All rights reserved.

The Parker-Sochacki Method--A Powerful New Method for Solving Systems of Differential Equations

NASA Astrophysics Data System (ADS)

Rudmin, Joseph W.

2001-04-01

The Parker-Sochacki Method--A Powerful New Method for Solving Systems of Differential Equations Joseph W. Rudmin (Physics Dept, James Madison University) A new system of solving systems of differential equations will be presented, which has been developed by J. Edgar Parker and James Sochacki, of the James Madison University Mathematics Department. The method produces MacClaurin Series solutions to systems of differential equations, with the coefficients in either algebraic or numerical form. The method yields high-degree solutions: 20th degree is easily obtainable. It is conceptually simple, fast, and extremely general. It has been applied to over a hundred systems of differential equations, some of which were previously unsolved, and has yet to fail to solve any system for which the MacClaurin series converges. The method is non-recursive: each coefficient in the series is calculated just once, in closed form, and its accuracy is limited only by the digital accuracy of the computer. Although the original differential equations may include any mathematical functions, the computational method includes ONLY the operations of addition, subtraction, and multiplication. Furthermore, it is perfectly suited to parallel -processing computer languages. Those who learn this system will never use Runge-Kutta or predictor-corrector methods again. Examples will be presented, including the classical many-body problem.

Seven Steps to Responsible Software Selection. ERIC Digest.

ERIC Educational Resources Information Center

Komoski, P. Kenneth; Plotnick, Eric

Microcomputers in schools contribute significantly to the learning process, and software selection is taken as seriously as the selection of text books. The seven step process for responsible software selection are: (1) analyzing needs, including the differentiation between needs and objectives; (2) specification of requirements; (3) identifying…

Human genomic regions with exceptionally high levels of population differentiation identified from 911 whole-genome sequences.

PubMed

Colonna, Vincenza; Ayub, Qasim; Chen, Yuan; Pagani, Luca; Luisi, Pierre; Pybus, Marc; Garrison, Erik; Xue, Yali; Tyler-Smith, Chris; Abecasis, Goncalo R; Auton, Adam; Brooks, Lisa D; DePristo, Mark A; Durbin, Richard M; Handsaker, Robert E; Kang, Hyun Min; Marth, Gabor T; McVean, Gil A

2014-06-30

Population differentiation has proved to be effective for identifying loci under geographically localized positive selection, and has the potential to identify loci subject to balancing selection. We have previously investigated the pattern of genetic differentiation among human populations at 36.8 million genomic variants to identify sites in the genome showing high frequency differences. Here, we extend this dataset to include additional variants, survey sites with low levels of differentiation, and evaluate the extent to which highly differentiated sites are likely to result from selective or other processes. We demonstrate that while sites with low differentiation represent sampling effects rather than balancing selection, sites showing extremely high population differentiation are enriched for positive selection events and that one half may be the result of classic selective sweeps. Among these, we rediscover known examples, where we actually identify the established functional SNP, and discover novel examples including the genes ABCA12, CALD1 and ZNF804, which we speculate may be linked to adaptations in skin, calcium metabolism and defense, respectively. We identify known and many novel candidate regions for geographically restricted positive selection, and suggest several directions for further research.

Method and apparatus for differential spectroscopic atomic-imaging using scanning tunneling microscopy

DOEpatents

Kazmerski, Lawrence L.

1990-01-01

A Method and apparatus for differential spectroscopic atomic-imaging is disclosed for spatial resolution and imaging for display not only individual atoms on a sample surface, but also bonding and the specific atomic species in such bond. The apparatus includes a scanning tunneling microscope (STM) that is modified to include photon biasing, preferably a tuneable laser, modulating electronic surface biasing for the sample, and temperature biasing, preferably a vibration-free refrigerated sample mounting stage. Computer control and data processing and visual display components are also included. The method includes modulating the electronic bias voltage with and without selected photon wavelengths and frequency biasing under a stabilizing (usually cold) bias temperature to detect bonding and specific atomic species in the bonds as the STM rasters the sample. This data is processed along with atomic spatial topography data obtained from the STM raster scan to create a real-time visual image of the atoms on the sample surface.

Deep Learning Representation from Electroencephalography of Early-Stage Creutzfeldt-Jakob Disease and Features for Differentiation from Rapidly Progressive Dementia.

PubMed

Morabito, Francesco Carlo; Campolo, Maurizio; Mammone, Nadia; Versaci, Mario; Franceschetti, Silvana; Tagliavini, Fabrizio; Sofia, Vito; Fatuzzo, Daniela; Gambardella, Antonio; Labate, Angelo; Mumoli, Laura; Tripodi, Giovanbattista Gaspare; Gasparini, Sara; Cianci, Vittoria; Sueri, Chiara; Ferlazzo, Edoardo; Aguglia, Umberto

2017-03-01

A novel technique of quantitative EEG for differentiating patients with early-stage Creutzfeldt-Jakob disease (CJD) from other forms of rapidly progressive dementia (RPD) is proposed. The discrimination is based on the extraction of suitable features from the time-frequency representation of the EEG signals through continuous wavelet transform (CWT). An average measure of complexity of the EEG signal obtained by permutation entropy (PE) is also included. The dimensionality of the feature space is reduced through a multilayer processing system based on the recently emerged deep learning (DL) concept. The DL processor includes a stacked auto-encoder, trained by unsupervised learning techniques, and a classifier whose parameters are determined in a supervised way by associating the known category labels to the reduced vector of high-level features generated by the previous processing blocks. The supervised learning step is carried out by using either support vector machines (SVM) or multilayer neural networks (MLP-NN). A subset of EEG from patients suffering from Alzheimer's Disease (AD) and healthy controls (HC) is considered for differentiating CJD patients. When fine-tuning the parameters of the global processing system by a supervised learning procedure, the proposed system is able to achieve an average accuracy of 89%, an average sensitivity of 92%, and an average specificity of 89% in differentiating CJD from RPD. Similar results are obtained for CJD versus AD and CJD versus HC.

Integrated analysis of long noncoding RNA and mRNA expression profile in children with obesity by microarray analysis.

PubMed

Liu, Yuesheng; Ji, Yuqiang; Li, Min; Wang, Min; Yi, Xiaoqing; Yin, Chunyan; Wang, Sisi; Zhang, Meizhen; Zhao, Zhao; Xiao, Yanfeng

2018-06-08

Long noncoding RNAs (lncRNAs) have an important role in adipose tissue function and energy metabolism homeostasis, and abnormalities may lead to obesity. To investigate whether lncRNAs are involved in childhood obesity, we investigated the differential expression profile of lncRNAs in obese children compared with non-obese children. A total number of 1268 differentially expressed lncRNAs and 1085 differentially expressed mRNAs were identified. Gene Ontology (GO) and pathway analysis revealed that these lncRNAs were involved in varied biological processes, including the inflammatory response, lipid metabolic process, osteoclast differentiation and fatty acid metabolism. In addition, the lncRNA-mRNA co-expression network and the protein-protein interaction (PPI) network were constructed to identify hub regulatory lncRNAs and genes based on the microarray expression profiles. This study for the first time identifies an expression profile of differentially expressed lncRNAs in obese children and indicated hub lncRNA RP11-20G13.3 attenuated adipogenesis of preadipocytes, which is conducive to the search for new diagnostic and therapeutic strategies of childhood obesity.

Mandible shape and dwarfism in squirrels (Mammalia, Rodentia): interaction of allometry and adaptation

NASA Astrophysics Data System (ADS)

Hautier, Lionel; Fabre, Pierre-Henri; Michaux, Jacques

2009-06-01

Squirrels include several independent lineages of dwarf forms distributed into two ecological groups: the dwarf tree and flying squirrels. The mandible of dwarf tree squirrels share a highly reduced coronoid process and a condylar process drawn backwards. Dwarf flying squirrels on the other hand, have an elongated coronoid process and a well-differentiated condylar process. To interpret such a difference, Elliptic Fourier Transform was used to evaluate how mandible shape varies with dwarfism in sciurids. The results obtained show that this clear-cut difference cannot be explained by a simple allometric relationship in relation with size decrease. We concluded that the retention of anteriorly positioned eye sockets, in relation with distance estimation, allowed the conservation of a well-differentiated coronoid process in all flying species, despite the trend towards its reduction observed among sciurids as their size decreases.

FOXP2 drives neuronal differentiation by interacting with retinoic acid signaling pathways.

PubMed

Devanna, Paolo; Middelbeek, Jeroen; Vernes, Sonja C

2014-01-01

FOXP2 was the first gene shown to cause a Mendelian form of speech and language disorder. Although developmentally expressed in many organs, loss of a single copy of FOXP2 leads to a phenotype that is largely restricted to orofacial impairment during articulation and linguistic processing deficits. Why perturbed FOXP2 function affects specific aspects of the developing brain remains elusive. We investigated the role of FOXP2 in neuronal differentiation and found that FOXP2 drives molecular changes consistent with neuronal differentiation in a human model system. We identified a network of FOXP2 regulated genes related to retinoic acid signaling and neuronal differentiation. FOXP2 also produced phenotypic changes associated with neuronal differentiation including increased neurite outgrowth and reduced migration. Crucially, cells expressing FOXP2 displayed increased sensitivity to retinoic acid exposure. This suggests a mechanism by which FOXP2 may be able to increase the cellular differentiation response to environmental retinoic acid cues for specific subsets of neurons in the brain. These data demonstrate that FOXP2 promotes neuronal differentiation by interacting with the retinoic acid signaling pathway and regulates key processes required for normal circuit formation such as neuronal migration and neurite outgrowth. In this way, FOXP2, which is found only in specific subpopulations of neurons in the brain, may drive precise neuronal differentiation patterns and/or control localization and connectivity of these FOXP2 positive cells.

FOXP2 drives neuronal differentiation by interacting with retinoic acid signaling pathways

PubMed Central

Devanna, Paolo; Middelbeek, Jeroen; Vernes, Sonja C.

2014-01-01

FOXP2 was the first gene shown to cause a Mendelian form of speech and language disorder. Although developmentally expressed in many organs, loss of a single copy of FOXP2 leads to a phenotype that is largely restricted to orofacial impairment during articulation and linguistic processing deficits. Why perturbed FOXP2 function affects specific aspects of the developing brain remains elusive. We investigated the role of FOXP2 in neuronal differentiation and found that FOXP2 drives molecular changes consistent with neuronal differentiation in a human model system. We identified a network of FOXP2 regulated genes related to retinoic acid signaling and neuronal differentiation. FOXP2 also produced phenotypic changes associated with neuronal differentiation including increased neurite outgrowth and reduced migration. Crucially, cells expressing FOXP2 displayed increased sensitivity to retinoic acid exposure. This suggests a mechanism by which FOXP2 may be able to increase the cellular differentiation response to environmental retinoic acid cues for specific subsets of neurons in the brain. These data demonstrate that FOXP2 promotes neuronal differentiation by interacting with the retinoic acid signaling pathway and regulates key processes required for normal circuit formation such as neuronal migration and neurite outgrowth. In this way, FOXP2, which is found only in specific subpopulations of neurons in the brain, may drive precise neuronal differentiation patterns and/or control localization and connectivity of these FOXP2 positive cells. PMID:25309332

Ceres' Evolution Before and After Dawn: Where are We Now?

NASA Astrophysics Data System (ADS)

McCord, T. B.; Castillo, J. C.

2016-12-01

Observations of Ceres before Dawn indicated that it contains 25 wt% water, and thermodynamic modeling indicated Ceres probably had experienced the same process of differentiation due to melting of the original ice after accretion as experienced by large icy moons. Consistent with that was a surface of altered mineralogy like clays suggesting aqueous alteration of the original chondritic silicates. Dawn has revealed some concentration of mass toward the center, specific aqueously altered mineralogies, a stiff surface with weaker material beneath, and extrusions and protrusions suggesting recent subsurface activity, including exposures of water ice that must be very recent. This wealth of new information from Dawn enables selection of more specific evolution models that best match the vastly improved Dawn observations. In this new study we propose one possibility is that Ceres accreted as an ice and silicate mixture after short-lived radionuclides in CAIs had significantly decayed, i.e. nearer 5 my after CAIs, and thus differentiated less completely than for hotter models. On the other hand, the presence of heavily aqueously altered mineralogies, including probably salts, suggests extensive mixing of water and silicates, which might normally be associated with more complete differentiation. Geologically recent activity, perhaps even to the present time, seems evident from several young landforms, including protrusions consistent with diapirism and recent exposures of water ice. This suggests recent flexing of the subsurface and rising of less dense interior material, including salts and ice. The presence of ammoniated minerals and what appear to be salt deposits suggest a major lowering of subsurface water ice melting temperature, enhancing the duration of water-silicate contact, and perhaps accelerating the mineralization processes and slowing or halting differentiation of water and silicates. Thus, Ceres is becoming known as the first body outward from the Sun that has had its evolution controlled by water-driven processes. Investigations of its interior and geology enable by Dawn's observations will in turn help to better understand other ice-rich bodies.

Ceres' evolution before and after Dawn: Where are we now?

NASA Astrophysics Data System (ADS)

McCord, Thomas B.; Castillo-Rogez, Julie C.

2016-10-01

Observations of Ceres before Dawn indicated that it contains ~25 wt% water, and thermodynamic modeling indicated Ceres probably had experienced the same process of differentiation due to melting of the original ice after accretion as experienced by large icy moons. Consistent with that was a surface of altered mineralogy like clays suggesting aqueous alteration of the original chondritic silicates. Dawn has revealed some concentration of mass toward the center, specific aqueously altered mineralogies, a stiff surface with weaker material beneath, and extrusions and protrusions suggesting recent subsurface activity, including exposures of water ice that must be very recent. This wealth of new information from Dawn enables selection of more specific evolution models that best match the vastly improved Dawn observations. In this new study we propose one possibility is that Ceres accreted as an ice and silicate mixture after short-lived radionuclides in CAIs had significantly decayed, i.e. nearer 5 my after CAIs, and thus differentiated less completely than for hotter models. On the other hand, the presence of heavily aqueously altered mineralogies, including probably salts, suggests extensive mixing of water and silicates, which might normally be associated with more complete differentiation. Geologically recent activity, perhaps even to the present time, seems evident from several young landforms, including protrusions consistent with diapirism and recent exposures of water ice. This suggests recent flexing of the subsurface and rising of less dense interior material, including salts and ice. The presence of ammoniated minerals and what appear to be salt deposits suggest a major lowering of subsurface water ice melting temperature, enhancing the duration of water-silicate contact, and perhaps accelerating the mineralization processes and slowing or halting differentiation of water and silicates. Thus, Ceres is becoming known as the first body outward from the Sun that has had its evolution controlled by water-driven processes. Investigations of its interior and geology enable by Dawn's observations will in turn help to better understand other ice-rich bodies.

CTCF-Mediated and Pax6-Associated Gene Expression in Corneal Epithelial Cell-Specific Differentiation

PubMed Central

Tsui, Shanli; Wang, Jie; Wang, Ling; Dai, Wei; Lu, Luo

2016-01-01

Background The purpose of the study is to elicit the epigenetic mechanism involving CCCTC binding factor (CTCF)-mediated chromatin remodeling that regulates PAX6 gene interaction with differentiation-associated genes to control corneal epithelial differentiation. Methods Cell cycle progression and specific keratin expressions were measured to monitor changes of differentiation-induced primary human limbal stem/progenitor (HLS/P), human corneal epithelial (HCE) and human telomerase-immortalized corneal epithelial (HTCE) cells. PAX6-interactive and differentiation-associated genes in chromatin remodeling mediated by the epigenetic factor CTCF were detected by circular chromosome conformation capture (4C) and ChIP (Chromatin immunoprecipitation)-on-chip approaches, and verified by FISH (Fluorescent in situ hybridization). Furthermore, CTCF activities were altered by CTCF-shRNA to study the effect of CTCF on mediating interaction of Pax6 and differentiation-associated genes in corneal epithelial cell fate. Results Our results demonstrated that differentiation-induced human corneal epithelial cells expressed typical corneal epithelial characteristics including morphological changes, increased keratin12 expression and G0/G1 accumulations. Expressions of CTCF and PAX6 were suppressed and elevated following the process of differentiation, respectively. During corneal epithelial cell differentiation, differentiation-induced RCN1 and ADAM17 were found interacting with PAX6 in the process of CTCF-mediated chromatin remodeling detected by 4C and verified by ChIP-on-chip and FISH. Diminished CTCF mRNA with CTCF-shRNA in HTCE cells weakened the interaction of PAX6 gene in controlling RCN1/ADAM17 and enhanced early onset of the genes in cell differentiation. Conclusion Our results explain how epigenetic factor CTCF-mediated chromatin remodeling regulates interactions between eye-specific PAX6 and those genes that are induced/associated with cell differentiation to modulate corneal epithelial cell-specific differentiation. PMID:27583466

From embryonic stem cells to functioning germ cells: science, clinical and ethical perspectives.

PubMed

Kiatpongsan, Sorapop

2007-10-01

Embryonic stem cells have been well recognized as cells having a versatile potential to differentiate into all types of cells in the body including germ cells. There are many research studies focusing on the differentiation processes and protocols to derive various types of somatic cells from embryonic stem cells. However, germ cells have unique differentiation process and developmental pathway compared with somatic cells. Consequently, they will require different differentiation protocols and special culture techniques. More understanding and established in vitro systems for gametogenesis will greatly contribute to further progression of knowledge and technology in germ cell biology, reproductive biology and reproductive medicine. Moreover if oocytes can be efficiently produced in vitro, this will play an important role on progression in nuclear transfer and nuclear reprogramming technology. The present article will provide concise review on past important discoveries, current ongoing studies and future views of this challenging research area. An ethical perspective has also been proposed to give comprehensive summary and viewpoint for future clinical application.

Similarities and Differences in Adolescent Siblings’ Alcohol-Related Attitudes, Use, and Delinquency: Evidence for Convergent and Divergent Influence Processes

PubMed Central

Whiteman, Shawn D.; Jensen, Alexander C.; Maggs, Jennifer L.

2013-01-01

A growing body of research indicates that siblings influence each other’s risky and deviant behaviors during adolescence. Guided by research and theory on sibling similarities and differences, this study examined the operation and implications of three different influence processes--social learning, shared friends, and sibling differentiation--during adolescence. Participants included one parent and two adolescent siblings (earlier born age: M = 17.17 years, SD = 0.94; later born age: M = 14.52 years, SD = 1.27) from 326 families. Data were collected via telephone interviews. Using reports from both older and younger siblings, two-stage cluster analyses revealed three influence profiles: mutual modeling and shared friends, younger sibling admiration, and differentiation. Additional analyses revealed that mutual modeling and shared friends as well as younger sibling admiration were linked to similarities in brothers’ and sisters’ health-risk behaviors and attitudes, whereas differentiation processes were associated with divergence in siblings’ characteristics. The discussion focuses on refining the study of sibling influence, with particular attention paid to the operation and implications of both convergent and divergent influence processes. PMID:23765197

Process and domain specificity in regions engaged for face processing: an fMRI study of perceptual differentiation.

PubMed

Collins, Heather R; Zhu, Xun; Bhatt, Ramesh S; Clark, Jonathan D; Joseph, Jane E

2012-12-01

The degree to which face-specific brain regions are specialized for different kinds of perceptual processing is debated. This study parametrically varied demands on featural, first-order configural, or second-order configural processing of faces and houses in a perceptual matching task to determine the extent to which the process of perceptual differentiation was selective for faces regardless of processing type (domain-specific account), specialized for specific types of perceptual processing regardless of category (process-specific account), engaged in category-optimized processing (i.e., configural face processing or featural house processing), or reflected generalized perceptual differentiation (i.e., differentiation that crosses category and processing type boundaries). ROIs were identified in a separate localizer run or with a similarity regressor in the face-matching runs. The predominant principle accounting for fMRI signal modulation in most regions was generalized perceptual differentiation. Nearly all regions showed perceptual differentiation for both faces and houses for more than one processing type, even if the region was identified as face-preferential in the localizer run. Consistent with process specificity, some regions showed perceptual differentiation for first-order processing of faces and houses (right fusiform face area and occipito-temporal cortex and right lateral occipital complex), but not for featural or second-order processing. Somewhat consistent with domain specificity, the right inferior frontal gyrus showed perceptual differentiation only for faces in the featural matching task. The present findings demonstrate that the majority of regions involved in perceptual differentiation of faces are also involved in differentiation of other visually homogenous categories.

Process- and Domain-Specificity in Regions Engaged for Face Processing: An fMRI Study of Perceptual Differentiation

PubMed Central

Collins, Heather R.; Zhu, Xun; Bhatt, Ramesh S.; Clark, Jonathan D.; Joseph, Jane E.

2015-01-01

The degree to which face-specific brain regions are specialized for different kinds of perceptual processing is debated. The present study parametrically varied demands on featural, first-order configural or second-order configural processing of faces and houses in a perceptual matching task to determine the extent to which the process of perceptual differentiation was selective for faces regardless of processing type (domain-specific account), specialized for specific types of perceptual processing regardless of category (process-specific account), engaged in category-optimized processing (i.e., configural face processing or featural house processing) or reflected generalized perceptual differentiation (i.e. differentiation that crosses category and processing type boundaries). Regions of interest were identified in a separate localizer run or with a similarity regressor in the face-matching runs. The predominant principle accounting for fMRI signal modulation in most regions was generalized perceptual differentiation. Nearly all regions showed perceptual differentiation for both faces and houses for more than one processing type, even if the region was identified as face-preferential in the localizer run. Consistent with process-specificity, some regions showed perceptual differentiation for first-order processing of faces and houses (right fusiform face area and occipito-temporal cortex, and right lateral occipital complex), but not for featural or second-order processing. Somewhat consistent with domain-specificity, the right inferior frontal gyrus showed perceptual differentiation only for faces in the featural matching task. The present findings demonstrate that the majority of regions involved in perceptual differentiation of faces are also involved in differentiation of other visually homogenous categories. PMID:22849402

Mars Science Laboratory Differential Restraint: The Devil is in the Details

NASA Technical Reports Server (NTRS)

Jordan, Elizabeth

2012-01-01

The Differential Restraint, a mechanism used on the Mars Science Laboratory (MSL) rover to maintain symmetry of the mobility system during the launch, cruise, and entry descent and landing phases of the MSL mission, completed nearly three full design cycles before a finalized successful design was achieved. This paper address the lessons learned through these design cycles, including three major design elements that can easily be overlooked during the design process, including, tolerance stack contribution to load path, the possibility of Martian dirt as a failure mode, and the effects of material properties at temperature extremes.

Generation of Cardiomyocytes from Pluripotent Stem Cells.

PubMed

Nakahama, Hiroko; Di Pasquale, Elisa

2016-01-01

The advent of pluripotent stem cells (PSCs) enabled a multitude of studies for modeling the development of diseases and testing pharmaceutical therapeutic potential in vitro. These PSCs have been differentiated to multiple cell types to demonstrate its pluripotent potential, including cardiomyocytes (CMs). However, the efficiency and efficacy of differentiation vary greatly between different cell lines and methods. Here, we describe two different methods for acquiring CMs from human pluripotent lines. One method involves the generation of embryoid bodies, which emulates the natural developmental process, while the other method chemically activates the canonical Wnt signaling pathway to induce a monolayer of cardiac differentiation.

Meeting the needs of an ever-demanding market.

PubMed

Rigby, Richard

2002-04-01

Balancing cost and performance in packaging is critical. This article outlines techniques to assist in this whilst delivering added value and product differentiation. The techniques include a rigorous statistical process capable of delivering cost reduction and improved quality and a computer modelling process that can save time when validating new packaging options.

MicroRNA-432 contributes to dopamine cocktail and retinoic acid induced differentiation of human neuroblastoma cells by targeting NESTIN and RCOR1 genes.

PubMed

Das, Eashita; Bhattacharyya, Nitai Pada

2014-05-02

MicroRNA (miRNA) regulates expression of protein coding genes and has been implicated in diverse cellular processes including neuronal differentiation, cell growth and death. To identify the role of miRNA in neuronal differentiation, SH-SY5Y and IMR-32 cells were treated with dopamine cocktail and retinoic acid to induce differentiation. Detection of miRNAs in differentiated cells revealed that expression of many miRNAs was altered significantly. Among the altered miRNAs, human brain expressed miR-432 induced neurite projections, arrested cells in G0-G1, reduced cell proliferation and could significantly repress NESTIN/NES, RCOR1/COREST and MECP2. Our results reveal that miR-432 regulate neuronal differentiation of human neuroblastoma cells. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Theoretical Foundation for Weld Modeling

NASA Technical Reports Server (NTRS)

Traugott, S.

1986-01-01

Differential equations describe physics of tungsten/inert-gas and plasma-arc welding in aluminum. Report collects and describes necessary theoretical foundation upon which numerical welding model is constructed for tungsten/inert gas or plasma-arc welding in aluminum without keyhole. Governing partial differential equations for flow of heat, metal, and current given, together with boundary conditions relevant to welding process. Numerical estimates for relative importance of various phenomena and required properties of 2219 aluminum included

Gene expression profile in human induced pluripotent stem cells: Chondrogenic differentiation in vitro, part A

PubMed Central

Suchorska, Wiktoria Maria; Augustyniak, Ewelina; Richter, Magdalena; Trzeciak, Tomasz

2017-01-01

Human induced pluripotent stem cells (hiPSCs) offer promise in regenerative medicine, however more data are required to improve understanding of key aspects of the cell differentiation process, including how specific chondrogenic processes affect the gene expression profile of chondrocyte-like cells and the relative value of cell differentiation markers. The main aims of the present study were as follows: To determine the gene expression profile of chondrogenic-like cells derived from hiPSCs cultured in mediums conditioned with HC-402-05a cells or supplemented with transforming growth factor β3 (TGF-β3), and to assess the relative utility of the most commonly used chondrogenic markers as indicators of cell differentiation. These issues are relevant with regard to the use of human fibroblasts in the reprogramming process to obtain hiPSCs. Human fibroblasts are derived from the mesoderm and thus share a wide range of properties with chondrocytes, which also originate from the mesenchyme. Thus, the exclusion of dedifferentiation instead of chondrogenic differentiation is crucial. The hiPSCs were obtained from human primary dermal fibroblasts during a reprogramming process. Two methods, both involving embryoid bodies (EB), were used to obtain chondrocytes from the hiPSCs: EBs formed in a chondrogenic medium supplemented with TGF-β3 (10 ng/ml) and EBs formed in a medium conditioned with growth factors from HC-402-05a cells. Based on immunofluorescence and reverse transcription-quantiative polymerase chain reaction analysis, the results indicated that hiPSCs have the capacity for effective chondrogenic differentiation, in particular cells differentiated in the HC-402-05a-conditioned medium, which present morphological features and markers that are characteristic of mature human chondrocytes. By contrast, cells differentiated in the presence of TGF-β3 may demonstrate hypertrophic characteristics. Several genes [paired box 9, sex determining region Y-box (SOX) 5, SOX6, SOX9 and cartilage oligomeric matrix protein] were demonstrated to be good markers of early hiPSC chondrogenic differentiation: Insulin-like growth factor 1, Tenascin-C, and β-catenin were less valuable. These observations provide valuable data on the use of hiPSCs in cartilage tissue regeneration. PMID:28447755

Regulation of Mesenchymal Stem Cell Differentiation by Nanopatterning of Bulk Metallic Glass.

PubMed

Loye, Ayomiposi M; Kinser, Emily R; Bensouda, Sabrine; Shayan, Mahdis; Davis, Rose; Wang, Rui; Chen, Zheng; Schwarz, Udo D; Schroers, Jan; Kyriakides, Themis R

2018-06-08

Mesenchymal stem cell (MSC) differentiation is regulated by surface modification including texturing, which is applied to materials to enhance tissue integration. Here, we used Pt 57.5 Cu 14.7 Ni 5.3 P 22.5 bulk metallic glass (Pt-BMG) with nanopatterned surfaces achieved by thermoplastic forming to influence differentiation of human MSCs. Pt-BMGs are a unique class of amorphous metals with high strength, elasticity, corrosion resistance, and an unusual plastic-like processability. It was found that flat and nanopattened Pt-BMGs induced osteogenic and adipogenic differentiation, respectively. In addition, osteogenic differentiation on flat BMG exceeded that observed on medical grade titanium and was associated with increased formation of focal adhesions and YAP nuclear localization. In contrast, cells on nanopatterned BMGs exhibited rounded morphology, formed less focal adhesions and had mostly cytoplasmic YAP. These changes were preserved on nanopatterns made of nanorods with increased stiffness due to shorter aspect ratios, suggesting that MSC differentiation was primarily influenced by topography. These observations indicate that both elemental composition and nanotopography can modulate biochemical cues and influence MSCs. Moreover, the processability and highly tunable nature of Pt-BMGs enables the creation of a wide range of surface topographies that can be reproducibly and systematically studied, leading to the development of implants capable of engineering MSC functions.

Knocking down of heat-shock protein 27 directs differentiation of functional glutamatergic neurons from placenta-derived multipotent cells

PubMed Central

Cheng, Yu-Che; Huang, Chi-Jung; Lee, Yih-Jing; Tien, Lu-Tai; Ku, Wei-Chi; Chien, Raymond; Lee, Fa-Kung; Chien, Chih-Cheng

2016-01-01

This study presents human placenta-derived multipotent cells (PDMCs) as a source from which functional glutamatergic neurons can be derived. We found that the small heat-shock protein 27 (HSP27) was downregulated during the neuronal differentiation process. The in vivo temporal and spatial profiles of HSP27 expression were determined and showed inverted distributions with neuronal proteins during mouse embryonic development. Overexpression of HSP27 in stem cells led to the arrest of neuronal differentiation; however, the knockdown of HSP27 yielded a substantially enhanced ability of PDMCs to differentiate into neurons. These neurons formed synaptic networks and showed positive staining for multiple neuronal markers. Additionally, cellular phenomena including the absence of apoptosis and rare proliferation in HSP27-silenced PDMCs, combined with molecular events such as cleaved caspase-3 and the loss of stemness with cleaved Nanog, indicated that HSP27 is located upstream of neuronal differentiation and constrains that process. Furthermore, the induced neurons showed increasing intracellular calcium concentrations upon glutamate treatment. These differentiated cells co-expressed the N-methyl-D-aspartate receptor, vesicular glutamate transporter, and synaptosomal-associated protein 25 but did not show expression of tyrosine hydroxylase, choline acetyltransferase or glutamate decarboxylase 67. Therefore, we concluded that HSP27-silenced PDMCs differentiated into neurons possessing the characteristics of functional glutamatergic neurons. PMID:27444754

Nucleosomal occupancy changes locally over key regulatory regions during cell differentiation and reprogramming.

PubMed

West, Jason A; Cook, April; Alver, Burak H; Stadtfeld, Matthias; Deaton, Aimee M; Hochedlinger, Konrad; Park, Peter J; Tolstorukov, Michael Y; Kingston, Robert E

2014-08-27

Chromatin structure determines DNA accessibility. We compare nucleosome occupancy in mouse and human embryonic stem cells (ESCs), induced-pluripotent stem cells (iPSCs) and differentiated cell types using MNase-seq. To address variability inherent in this technique, we developed a bioinformatic approach to identify regions of difference (RoD) in nucleosome occupancy between pluripotent and somatic cells. Surprisingly, most chromatin remains unchanged; a majority of rearrangements appear to affect a single nucleosome. RoDs are enriched at genes and regulatory elements, including enhancers associated with pluripotency and differentiation. RoDs co-localize with binding sites of key developmental regulators, including the reprogramming factors Klf4, Oct4/Sox2 and c-Myc. Nucleosomal landscapes in ESC enhancers are extensively altered, exhibiting lower nucleosome occupancy in pluripotent cells than in somatic cells. Most changes are reset during reprogramming. We conclude that changes in nucleosome occupancy are a hallmark of cell differentiation and reprogramming and likely identify regulatory regions essential for these processes.

microRNAs as regulators of adipogenic differentiation of mesenchymal stem cells.

PubMed

Hamam, Dana; Ali, Dalia; Kassem, Moustapha; Aldahmash, Abdullah; Alajez, Nehad M

2015-02-15

microRNAs (miRNAs) constitute complex regulatory network, fine tuning the expression of a myriad of genes involved in different biological and physiological processes, including stem cell differentiation. Mesenchymal stem cells (MSCs) are multipotent stem cells present in the bone marrow stroma, and the stroma of many other tissues, and can give rise to a number of mesoderm-type cells including adipocytes and osteoblasts, which form medullary fat and bone tissues, respectively. The role of bone marrow fat in bone mass homeostasis is an area of intensive investigation with the aim of developing novel approaches for enhancing osteoblastic bone formation through inhibition of bone marrow fat formation. A number of recent studies have reported several miRNAs that enhance or inhibit adipogenic differentiation of MSCs and with potential use in microRNA-based therapy to regulate adipogenesis in the context of treating bone diseases and metabolic disorders. The current review focuses on miRNAs and their role in regulating adipogenic differentiation of MSCs.

A model of the regulatory network involved in the control of the cell cycle and cell differentiation in the Caenorhabditis elegans vulva.

PubMed

Weinstein, Nathan; Ortiz-Gutiérrez, Elizabeth; Muñoz, Stalin; Rosenblueth, David A; Álvarez-Buylla, Elena R; Mendoza, Luis

2015-03-13

There are recent experimental reports on the cross-regulation between molecules involved in the control of the cell cycle and the differentiation of the vulval precursor cells (VPCs) of Caenorhabditis elegans. Such discoveries provide novel clues on how the molecular mechanisms involved in the cell cycle and cell differentiation processes are coordinated during vulval development. Dynamic computational models are helpful to understand the integrated regulatory mechanisms affecting these cellular processes. Here we propose a simplified model of the regulatory network that includes sufficient molecules involved in the control of both the cell cycle and cell differentiation in the C. elegans vulva to recover their dynamic behavior. We first infer both the topology and the update rules of the cell cycle module from an expected time series. Next, we use a symbolic algorithmic approach to find which interactions must be included in the regulatory network. Finally, we use a continuous-time version of the update rules for the cell cycle module to validate the cyclic behavior of the network, as well as to rule out the presence of potential artifacts due to the synchronous updating of the discrete model. We analyze the dynamical behavior of the model for the wild type and several mutants, finding that most of the results are consistent with published experimental results. Our model shows that the regulation of Notch signaling by the cell cycle preserves the potential of the VPCs and the three vulval fates to differentiate and de-differentiate, allowing them to remain completely responsive to the concentration of LIN-3 and lateral signal in the extracellular microenvironment.

Trait anxiety and attenuated negative affect differentiation: a vulnerability factor to consider?

PubMed

Matt, Lindsey M; Fresco, David M; Coifman, Karin G

2016-11-01

Describing emotional experiences using distinct terms, or affect differentiation, has been associated with emotion regulation and adaptive behavior under stress. There is little data, however, examining the association between differentiation and dispositional factors underlying psychopathology. The current study examines the association between differentiation and trait anxiety (TA) given prior evidence of cognitive biases in TA relevant to higher order processing of emotional experiences. We examined cross-sectionally, via lab-based repeated assessment, the association between differentiation of negative and positive experiences and TA. Two hundred twenty-two adults completed an emotion reactivity task including repeated assessments of affect. We hypothesized that individuals higher in trait anxiety (HTA) would have greater difficulty differentiating their experiences. HTA individuals exhibited lower levels of negative affect (NA) differentiation even when controlling for depression. Although negative emotion intensity was consistently associated with lower differentiation, this did not account for the influence of HTA on differentiation. These data suggest that HTA individuals have greater difficulty differentiating negative emotions, regardless of negative emotion intensity and depression. As HTA is common to many emotional disorders; this evidence suggests that poor differentiation may also be an important transdiagnostic consideration in models of risk and of affective disease.

Raw and processed ground-penetrating radar and postprocessed differential global positioning system data collected from Assateague Island, Maryland, October 2014

USGS Publications Warehouse

Zaremba, Nicholas J.; Bernier, Julie C.; Forde, Arnell S.; Smith, Christopher G.

2016-06-08

This report serves as an archive of GPR and DGPS data collected from Assateague Island in October 2014. Data products, including raw GPR and processed DGPS data, elevation corrected GPR profiles, and accompanying Federal Geographic Data Committee metadata can be downloaded from the Data Downloads page.

Representational Explanations of "Process" Dissociations in Recognition: The DRYAD Theory of Aging and Memory Judgments

ERIC Educational Resources Information Center

Benjamin, Aaron S.

2010-01-01

It is widely assumed that older adults suffer a deficit in the psychological processes that underlie remembering of contextual or source information. This conclusion is based in large part on empirical interactions, including disordinal ones, that reveal differential effects of manipulations of memory strength on recognition in young and old…

Experimental Test of the Differential Fluctuation Theorem and a Generalized Jarzynski Equality for Arbitrary Initial States

NASA Astrophysics Data System (ADS)

Hoang, Thai M.; Pan, Rui; Ahn, Jonghoon; Bang, Jaehoon; Quan, H. T.; Li, Tongcang

2018-02-01

Nonequilibrium processes of small systems such as molecular machines are ubiquitous in biology, chemistry, and physics but are often challenging to comprehend. In the past two decades, several exact thermodynamic relations of nonequilibrium processes, collectively known as fluctuation theorems, have been discovered and provided critical insights. These fluctuation theorems are generalizations of the second law and can be unified by a differential fluctuation theorem. Here we perform the first experimental test of the differential fluctuation theorem using an optically levitated nanosphere in both underdamped and overdamped regimes and in both spatial and velocity spaces. We also test several theorems that can be obtained from it directly, including a generalized Jarzynski equality that is valid for arbitrary initial states, and the Hummer-Szabo relation. Our study experimentally verifies these fundamental theorems and initiates the experimental study of stochastic energetics with the instantaneous velocity measurement.

Three-Dimensional Coculture Of Human Small-Intestine Cells

NASA Technical Reports Server (NTRS)

Wolf, David; Spaulding, Glen; Goodwin, Thomas J.; Prewett, Tracy

1994-01-01

Complex three-dimensional masses of normal human epithelial and mesenchymal small-intestine cells cocultured in process involving specially designed bioreactors. Useful as tissued models for studies of growth, regulatory, and differentiation processes in normal intestinal tissues; diseases of small intestine; and interactions between cells of small intestine and viruses causing disease both in small intestine and elsewhere in body. Process used to produce other tissue models, leading to advances in understanding of growth and differentiation in developing organisms, of renewal of tissue, and of treatment of myriad of clinical conditions. Prior articles describing design and use of rotating-wall culture vessels include "Growing And Assembling Cells Into Tissues" (MSC-21559), "High-Aspect-Ratio Rotating Cell-Culture Vessel" (MSC-21662), and "In Vitro, Matrix-Free Formation Of Solid Tumor Spheroids" (MSC-21843).

Diagnostic techniques in deflagration and detonation studies.

PubMed

Proud, William G; Williamson, David M; Field, John E; Walley, Stephen M

2015-12-01

Advances in experimental, high-speed techniques can be used to explore the processes occurring within energetic materials. This review describes techniques used to study a wide range of processes: hot-spot formation, ignition thresholds, deflagration, sensitivity and finally the detonation process. As this is a wide field the focus will be on small-scale experiments and quantitative studies. It is important that such studies are linked to predictive models, which inform the experimental design process. The stimuli range includes, thermal ignition, drop-weight, Hopkinson Bar and Plate Impact studies. Studies made with inert simulants are also included as these are important in differentiating between reactive response and purely mechanical behaviour.

Identification of Differentially Expressed miRNAs between White and Black Hair Follicles by RNA-Sequencing in the Goat (Capra hircus)

PubMed Central

Wu, Zhenyang; Fu, Yuhua; Cao, Jianhua; Yu, Mei; Tang, Xiaohui; Zhao, Shuhong

2014-01-01

MicroRNAs (miRNAs) play a key role in many biological processes by regulating gene expression at the post-transcriptional level. A number of miRNAs have been identified from livestock species. However, compared with other animals, such as pigs and cows, the number of miRNAs identified in goats is quite low, particularly in hair follicles. In this study, to investigate the functional roles of miRNAs in goat hair follicles of goats with different coat colors, we sequenced miRNAs from two hair follicles samples (white and black) using Solexa sequencing. A total of 35,604,016 reads were obtained, which included 30,878,637 clean reads (86.73%). MiRDeep2 software identified 214 miRNAs. Among them, 205 were conserved among species and nine were novel miRNAs. Furthermore, DESeq software identified six differentially expressed miRNAs. Quantitative PCR confirmed differential expression of two miRNAs, miR-10b and miR-211. KEGG pathways were analyzed using the DAVID website for the predicted target genes of the differentially expressed miRNAs. Several signaling pathways including Notch and MAPK pathways may affect the process of coat color formation. Our study showed that the identified miRNAs might play an essential role in black and white follicle formation in goats. PMID:24879525

Temporal analysis of reciprocal miRNA-mRNA expression patterns predicts regulatory networks during differentiation in human skeletal muscle cells

PubMed Central

Sjögren, Rasmus J. O.; Egan, Brendan; Katayama, Mutsumi; Zierath, Juleen R.

2014-01-01

microRNAs (miRNAs) are short noncoding RNAs that regulate gene expression through posttranscriptional repression of target genes. miRNAs exert a fundamental level of control over many developmental processes, but their role in the differentiation and development of skeletal muscle from myogenic progenitor cells in humans remains incompletely understood. Using primary cultures established from human skeletal muscle satellite cells, we performed microarray profiling of miRNA expression during differentiation of myoblasts (day 0) into myotubes at 48 h intervals (day 2, 4, 6, 8, and 10). Based on a time-course analysis, we identified 44 miRNAs with altered expression [false discovery rate (FDR) < 5%, fold change > ±1.2] during differentiation, including the marked upregulation of the canonical myogenic miRNAs miR-1, miR-133a, miR-133b, and miR-206. Microarray profiling of mRNA expression at day 0, 4, and 10 identified 842 and 949 genes differentially expressed (FDR < 10%) at day 4 and 10, respectively. At day 10, 42% of altered transcripts demonstrated reciprocal expression patterns in relation to the directional change of their in silico predicted regulatory miRNAs based on analysis using Ingenuity Pathway Analysis microRNA Target Filter. Bioinformatic analysis predicted networks of regulation during differentiation including myomiRs miR-1/206 and miR-133a/b, miRNAs previously established in differentiation including miR-26 and miR-30, and novel miRNAs regulated during differentiation of human skeletal muscle cells such as miR-138-5p and miR-20a. These reciprocal expression patterns may represent new regulatory nodes in human skeletal muscle cell differentiation. This analysis serves as a reference point for future studies of human skeletal muscle differentiation and development in healthy and disease states. PMID:25547110

Smoke-related DNA methylation changes in the etiology of human disease.

PubMed

Besingi, Welisane; Johansson, Asa

2014-05-01

Exposure to environmental and lifestyle factors, such as cigarette smoking, affect the epigenome and might mediate risk for diseases and cancers. We have performed a genome-wide DNA methylation study to determine the effect of smoke and snuff (smokeless tobacco) on DNA methylation. A total of 95 sites were differentially methylated [false discovery rate (FDR) q-values < 0.05] in smokers and a subset of the differentially methylated loci were also differentially expressed in smokers. We found no sites, neither any biological functions nor molecular processes enriched for smoke-less tobacco-related differential DNA methylation. This suggests that methylation changes are not caused by the basic components of the tobacco but from its burnt products. Instead, we see a clear enrichment (FDR q-value < 0.05) for genes, including CPOX, CDKN1A and PTK2, involved in response to arsenic-containing substance, which agrees with smoke containing small amounts of arsenic. A large number of biological functions and molecular processes with links to disease conditions are also enriched (FDR q-value < 0.05) for smoke-related DNA methylation changes. These include 'insulin receptor binding', and 'negative regulation of glucose import' which are associated with diabetes, 'positive regulation of interleukin-6-mediated signaling pathway', 'regulation of T-helper 2 cell differentiation', 'positive regulation of interleukin-13 production' which are associated with the immune system and 'sertoli cell fate commitment' which is important for male fertility. Since type 2 diabetes, repressed immune system and infertility have previously been associated with smoking, our results suggest that this might be mediated by DNA methylation changes.

Discrimination of emotional facial expressions by tufted capuchin monkeys (Sapajus apella).

PubMed

Calcutt, Sarah E; Rubin, Taylor L; Pokorny, Jennifer J; de Waal, Frans B M

2017-02-01

Tufted or brown capuchin monkeys (Sapajus apella) have been shown to recognize conspecific faces as well as categorize them according to group membership. Little is known, though, about their capacity to differentiate between emotionally charged facial expressions or whether facial expressions are processed as a collection of features or configurally (i.e., as a whole). In 3 experiments, we examined whether tufted capuchins (a) differentiate photographs of neutral faces from either affiliative or agonistic expressions, (b) use relevant facial features to make such choices or view the expression as a whole, and (c) demonstrate an inversion effect for facial expressions suggestive of configural processing. Using an oddity paradigm presented on a computer touchscreen, we collected data from 9 adult and subadult monkeys. Subjects discriminated between emotional and neutral expressions with an exceptionally high success rate, including differentiating open-mouth threats from neutral expressions even when the latter contained varying degrees of visible teeth and mouth opening. They also showed an inversion effect for facial expressions, results that may indicate that quickly recognizing expressions does not originate solely from feature-based processing but likely a combination of relational processes. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

ZNF750 is a p63 Target Gene that Induces KLF4 to Drive Terminal Epidermal Differentiation

PubMed Central

Sen, George L.; Boxer, Lisa D.; Webster, Dan E.; Bussat, Rose T.; Qu, Kun; Zarnegar, Brian J.; Johnston, Danielle; Siprashvili, Zurab; Khavari, Paul A.

2012-01-01

SUMMARY Disrupted epidermal differentiation characterizes numerous diseases that impact >25% of the population. In a search for dominant mediators of differentiation, we defined a requirement for ZNF750 in terminal epidermal differentiation. ZNF750 controlled genes mutated in numerous human skin diseases, including FLG, LOR, LCE3B, ALOXE3, and SPINK5. ZNF750 induced progenitor differentiation via an evolutionarily conserved C2H2 zinc finger motif. The epidermal master regulator, p63, bound the ZNF750 promoter and was necessary for its induction. ZNF750 restored differentiation to p63-deficient tissue, suggesting it acts downstream of p63. A search for functionally important ZNF750 targets via analysis of ZNF750-regulated genes identified KLF4, a transcription factor that activates late epidermal differentiation. ZNF750 binds to KLF4 at multiple sites flanking the transcriptional start site and controls its expression. ZNF750 thus directly links a tissue-specifying factor, p63, to an effector of terminal differentiation, KLF4, and represents a potential future target for disorders of this process. PMID:22364861

Differentiation and Characterization of Myeloid Cells

PubMed Central

Gupta, Dipti; Shah, Hetavi Parag; Malu, Krishnakumar; Berliner, Nancy; Gaines, Peter

2015-01-01

Recent molecular studies of myeloid differentiation have utilized several in vitro models of myelopoiesis, generated from either ex vivo differentiated bone marrow progenitors or induced immortalized myeloid cell lines. Ex vivo differentiation begins with an enriched population of bone marrow-derived hematopoietic stem cells generated by lineage depletion and/or positive selection for CD34+ antigen (human) or Sca-1+ (mouse) cells, which are then expanded and subsequently induced in vitro in a process that recapitulates normal myeloid development. Myeloid cell lines include two human leukemic cell lines, NB-4 and HL-60, which have been demonstrated to undergo retinoic acid–induced myeloid development, however, both cell lines exhibit defects in the upregulation of late-expressed neutrophil-specific genes. Multiple murine factor–dependent cell models of myelopoiesis are also available that express the full range of neutrophil maturation markers, including: 32Dcl3 cells, which undergo G-CSF-induced myeloid maturation, EML/EPRO cells, which develop into mature neutrophils in response to cytokines and retinoic acid, and ER-Hoxb8 cells, which undergo myeloid maturation upon removal of estradial in the maintenance medium. In this unit, the induction of myeloid maturation in each of these model systems is described, including their differentiation to either neutrophils or macrophages, if applicable. Commonly used techniques to test for myeloid characteristics of developing cells are also described, including flow cytometry and real time RT-PCR. Together, these assays provide a solid foundation for in vitro investigations of myeloid development with either human or mouse models. PMID:24510620

Vascular Regeneration in a Basal Chordate Is Due to the Presence of Immobile, Bi-Functional Cells

PubMed Central

Braden, Brian P.; Taketa, Daryl A.; Pierce, James D.; Kassmer, Susannah; Lewis, Daniel D.; De Tomaso, Anthony W.

2014-01-01

The source of tissue turnover during homeostasis or following injury is usually due to proliferation of a small number of resident, lineage-restricted stem cells that have the ability to amplify and differentiate into mature cell types. We are studying vascular regeneration in a chordate model organism, Botryllus schlosseri, and have previously found that following surgical ablation of the extracorporeal vasculature, new tissue will regenerate in a VEGF-dependent process within 48 hrs. Here we use a novel vascular cell lineage tracing methodology to assess regeneration in parabiosed individuals and demonstrate that the source of regenerated vasculature is due to the proliferation of pre-existing vascular resident cells and not a mobile progenitor. We also show that these cells are bi-potential, and can reversibly adopt two fates, that of the newly forming vessels or the differentiated vascular tissue at the terminus of the vasculature, known as ampullae. In addition, we show that pre-existing vascular resident cells differentially express progenitor and differentiated cell markers including the Botryllus homologs of CD133, VEGFR-2, and Cadherin during the regenerative process. PMID:24736432

Lipid deregulation in UV irradiated skin cells: Role of 25-hydroxycholesterol in keratinocyte differentiation during photoaging.

PubMed

Olivier, Elodie; Dutot, Mélody; Regazzetti, Anne; Dargère, Delphine; Auzeil, Nicolas; Laprévote, Olivier; Rat, Patrice

2017-05-01

Skin photoaging due to UV irradiation is a degenerative process that appears more and more as a growing concern. Lipids, including oxysterols, are involved in degenerative processes; as skin cells contain various lipids, the aim of our study was to evaluate first, changes in keratinocyte lipid levels induced by UV exposure and second, cellular effects of oxysterols in cell morphology and several hallmarks of keratinocyte differentiation. Our mass spectrometry results demonstrated that UV irradiation induces changes in lipid profile of cultured keratinocytes; in particular, ceramides and oxysterols, specifically 25-hydroxycholesterol (25-OH), were increased. Using holography and confocal microscopy analyses, we highlighted cell thickening and cytoskeletal disruption after incubation of keratinocytes with 25-OH. These alterations were associated with keratinocyte differentiation patterns: autophagy stimulation and intracellular calcium increase as measured by cytofluorometry, and increased involucrin level detected by immunocytochemistry. To conclude, oxysterol deregulation could be considered as a common marker of degenerative disorders. During photoaging, 25-OH seems to play a key role inducing morphological changes and keratinocyte differentiation. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Mouse androgenetic embryonic stem cells differentiated to multiple cell lineages in three embryonic germ layers in vitro.

PubMed

Teramura, Takeshi; Onodera, Yuta; Murakami, Hideki; Ito, Syunsuke; Mihara, Toshihiro; Takehara, Toshiyuki; Kato, Hiromi; Mitani, Tasuku; Anzai, Masayuki; Matsumoto, Kazuya; Saeki, Kazuhiro; Fukuda, Kanji; Sagawa, Norimasa; Osoi, Yoshihiko

2009-06-01

The embryos of some rodents and primates can precede early development without the process of fertilization; however, they cease to develop after implantation because of restricted expressions of imprinting genes. Asexually developed embryos are classified into parthenote/gynogenote and androgenote by their genomic origins. Embryonic stem cells (ESCs) derived from asexual origins have also been reported. To date, ESCs derived from parthenogenetic embryos (PgESCs) have been established in some species, including humans, and the possibility to be alternative sources for autologous cell transplantation in regenerative medicine has been proposed. However, some developmental characteristics, which might be important for therapeutic applications, such as multiple differentiation capacity and transplantability of the ESCs of androgenetic origin (AgESCs) are uncertain. Here, we induced differentiation of mouse AgESCs and observed derivation of neural cells, cardiomyocytes and hepatocytes in vitro. Following differentiated embryoid body (EB) transplantation in various mouse strains including the strain of origin, we found that the EBs could engraft in theoretically MHC-matched strains. Our results indicate that AgESCs possess at least two important characteristics, multiple differentiation properties in vitro and transplantability after differentiation, and suggest that they can also serve as a source of histocompatible tissues for transplantation.

Gene expression profiles of fin regeneration in loach (Paramisgurnus dabryanu).

PubMed

Li, Li; He, Jingya; Wang, Linlin; Chen, Weihua; Chang, Zhongjie

2017-11-01

Teleost fins can regenerate accurate position-matched structure and function after amputation. However, we still lack systematic transcriptional profiling and methodologies to understand the molecular basis of fin regeneration. After histological analysis, we established a suppression subtraction hybridization library containing 418 distinct sequences expressed differentially during the process of blastema formation and differentiation in caudal fin regeneration. Genome ontology and comparative analysis of differential distribution of our data and the reference zebrafish genome showed notable subcategories, including multi-organism processes, response to stimuli, extracellular matrix, antioxidant activity, and cell junction function. KEGG pathway analysis allowed the effective identification of relevant genes in those pathways involved in tissue morphogenesis and regeneration, including tight junction, cell adhesion molecules, mTOR and Jak-STAT signaling pathway. From relevant function subcategories and signaling pathways, 78 clones were examined for further Southern-blot hybridization. Then, 17 genes were chosen and characterized using semi-quantitative PCR. Then 4 candidate genes were identified, including F11r, Mmp9, Agr2 and one without a match to any database. After real-time quantitative PCR, the results showed obvious expression changes in different periods of caudal fin regeneration. We can assume that the 4 candidates, likely valuable genes associated with fin regeneration, deserve additional attention. Thus, our study demonstrated how to investigate the transcript profiles with an emphasis on bioinformatics intervention and how to identify potential genes related to fin regeneration processes. The results also provide a foundation or knowledge for further research into genes and molecular mechanisms of fin regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

Cryptic lineage differentiation among Indo-Pacific bottlenose dolphins (Tursiops aduncus) in the northwest Indian Ocean.

PubMed

Gray, H W I; Nishida, S; Welch, A J; Moura, A E; Tanabe, S; Kiani, M S; Culloch, R; Möller, L; Natoli, A; Ponnampalam, L S; Minton, G; Gore, M; Collins, T; Willson, A; Baldwin, R; Hoelzel, A R

2018-05-01

Phylogeography can provide insight into the potential for speciation and identify geographic regions and evolutionary processes associated with species richness and evolutionary endemism. In the marine environment, highly mobile species sometimes show structured patterns of diversity, but the processes isolating populations and promoting differentiation are often unclear. The Delphinidae (oceanic dolphins) are a striking case in point and, in particular, bottlenose dolphins (Tursiops spp.). Understanding the radiation of species in this genus is likely to provide broader inference about the processes that determine patterns of biogeography and speciation, because both fine-scale structure over a range of kilometers and relative panmixia over an oceanic range are known for Tursiops populations. In our study, novel Tursiops spp. sequences from the northwest Indian Ocean (including mitogenomes and two nuDNA loci) are included in a worldwide Tursiops spp. phylogeographic analysis. We discover a new 'aduncus' type lineage in the Arabian Sea (off India, Pakistan and Oman) that diverged from the Australasian lineage ∼261 Ka. Effective management of coastal dolphins in the region will need to consider this new lineage as an evolutionarily significant unit. We propose that the establishment of this lineage could have been in response to climate change during the Pleistocene and show data supporting hypotheses for multiple divergence events, including vicariance across the Indo-Pacific barrier and in the northwest Indian Ocean. These data provide valuable transferable inference on the potential mechanisms for population and species differentiation across this geographic range. Copyright © 2017 Elsevier Inc. All rights reserved.

Reward processing in neurodegenerative disease

PubMed Central

Perry, David C.; Kramer, Joel H.

2015-01-01

Representation of reward value involves a distributed network including cortical and subcortical structures. Because neurodegenerative illnesses target specific anatomic networks that partially overlap with the reward circuit they would be predicted to have distinct impairments in reward processing. This review presents the existing evidence of reward processing changes in neurodegenerative diseases including mild cognitive impairment, Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, Parkinson's disease, and Huntington's disease, as well as in healthy aging. Carefully distinguishing the different aspects of reward processing (primary rewards, secondary rewards, reward-based learning, and reward-based decision-making) and using tasks that differentiate the stages of processing reward will lead to improved understanding of this fundamental process and clarify a contributing cause of behavioral change in these illnesses. PMID:24417286

Performance Review of Harmony Search, Differential Evolution and Particle Swarm Optimization

NASA Astrophysics Data System (ADS)

Mohan Pandey, Hari

2017-08-01

Metaheuristic algorithms are effective in the design of an intelligent system. These algorithms are widely applied to solve complex optimization problems, including image processing, big data analytics, language processing, pattern recognition and others. This paper presents a performance comparison of three meta-heuristic algorithms, namely Harmony Search, Differential Evolution, and Particle Swarm Optimization. These algorithms are originated altogether from different fields of meta-heuristics yet share a common objective. The standard benchmark functions are used for the simulation. Statistical tests are conducted to derive a conclusion on the performance. The key motivation to conduct this research is to categorize the computational capabilities, which might be useful to the researchers.

Optimization of cDNA microarrays procedures using criteria that do not rely on external standards.

PubMed

Bruland, Torunn; Anderssen, Endre; Doseth, Berit; Bergum, Hallgeir; Beisvag, Vidar; Laegreid, Astrid

2007-10-18

The measurement of gene expression using microarray technology is a complicated process in which a large number of factors can be varied. Due to the lack of standard calibration samples such as are used in traditional chemical analysis it may be a problem to evaluate whether changes done to the microarray procedure actually improve the identification of truly differentially expressed genes. The purpose of the present work is to report the optimization of several steps in the microarray process both in laboratory practices and in data processing using criteria that do not rely on external standards. We performed a cDNA microarry experiment including RNA from samples with high expected differential gene expression termed "high contrasts" (rat cell lines AR42J and NRK52E) compared to self-self hybridization, and optimized a pipeline to maximize the number of genes found to be differentially expressed in the "high contrasts" RNA samples by estimating the false discovery rate (FDR) using a null distribution obtained from the self-self experiment. The proposed high-contrast versus self-self method (HCSSM) requires only four microarrays per evaluation. The effects of blocking reagent dose, filtering, and background corrections methodologies were investigated. In our experiments a dose of 250 ng LNA (locked nucleic acid) dT blocker, no background correction and weight based filtering gave the largest number of differentially expressed genes. The choice of background correction method had a stronger impact on the estimated number of differentially expressed genes than the choice of filtering method. Cross platform microarray (Illumina) analysis was used to validate that the increase in the number of differentially expressed genes found by HCSSM was real. The results show that HCSSM can be a useful and simple approach to optimize microarray procedures without including external standards. Our optimizing method is highly applicable to both long oligo-probe microarrays which have become commonly used for well characterized organisms such as man, mouse and rat, as well as to cDNA microarrays which are still of importance for organisms with incomplete genome sequence information such as many bacteria, plants and fish.

Optimization of cDNA microarrays procedures using criteria that do not rely on external standards

PubMed Central

Bruland, Torunn; Anderssen, Endre; Doseth, Berit; Bergum, Hallgeir; Beisvag, Vidar; Lægreid, Astrid

2007-01-01

Background The measurement of gene expression using microarray technology is a complicated process in which a large number of factors can be varied. Due to the lack of standard calibration samples such as are used in traditional chemical analysis it may be a problem to evaluate whether changes done to the microarray procedure actually improve the identification of truly differentially expressed genes. The purpose of the present work is to report the optimization of several steps in the microarray process both in laboratory practices and in data processing using criteria that do not rely on external standards. Results We performed a cDNA microarry experiment including RNA from samples with high expected differential gene expression termed "high contrasts" (rat cell lines AR42J and NRK52E) compared to self-self hybridization, and optimized a pipeline to maximize the number of genes found to be differentially expressed in the "high contrasts" RNA samples by estimating the false discovery rate (FDR) using a null distribution obtained from the self-self experiment. The proposed high-contrast versus self-self method (HCSSM) requires only four microarrays per evaluation. The effects of blocking reagent dose, filtering, and background corrections methodologies were investigated. In our experiments a dose of 250 ng LNA (locked nucleic acid) dT blocker, no background correction and weight based filtering gave the largest number of differentially expressed genes. The choice of background correction method had a stronger impact on the estimated number of differentially expressed genes than the choice of filtering method. Cross platform microarray (Illumina) analysis was used to validate that the increase in the number of differentially expressed genes found by HCSSM was real. Conclusion The results show that HCSSM can be a useful and simple approach to optimize microarray procedures without including external standards. Our optimizing method is highly applicable to both long oligo-probe microarrays which have become commonly used for well characterized organisms such as man, mouse and rat, as well as to cDNA microarrays which are still of importance for organisms with incomplete genome sequence information such as many bacteria, plants and fish. PMID:17949480

Identification of Phosphoproteins as Possible Differentiation Markers in All-Trans-Retinoic Acid-Treated Neuroblastoma Cells

PubMed Central

Mandili, Giorgia; Marini, Cristina; Carta, Franco; Zanini, Cristina; Prato, Mauro; Khadjavi, Amina

2011-01-01

Background Neuroblastic tumors account for 9–10% of pediatric tumors and neuroblastoma (NB) is the first cause of death in pre-school age children. NB is classified in four stages, depending on the extent of spreading. A fifth type of NB, so-called stage 4S (S for special), includes patients with metastatic tumors but with an overall survival that approximates 75% at five years. In most of these cases, the tumor regresses spontaneously and regression is probably associated with delayed neuroblast cell differentiation. Methodology/Principal Findings In order to identify new early markers to follow and predict this process for diagnostic and therapeutics intents, we mimicked the differentiation process treating NB cell line SJ-NK-P with all-trans-retinoic acid (ATRA) at different times; therefore the cell proteomic pattern by mass spectrometry and the phosphoproteomic pattern by a 2-DE approach coupled with anti-phosphoserine and anti-phosphotyrosine western blotting were studied. Conclusions/Significance Proteomic analysis identified only two proteins whose expression was significantly different in treated cells versus control cells: nucleoside diphosphate kinase A (NDKA) and reticulocalbin-1 (RCN1), which were both downregulated after 9 days of ATRA treatment. However, phosphoproteomic analysis identified 8 proteins that were differentially serine-phosphorylated and 3 that were differentially tyrosine-phosphorylated after ATRA treatment. All proteins were significantly regulated (at least 0.5-fold down-regulated). Our results suggest that differentially phosphorylated proteins could be considered as more promising markers of differentiation for NB than differentially expressed proteins. PMID:21573212

Glycoproteomic Analysis of Glioblastoma Stem Cell Differentiation

PubMed Central

He, Jintang; Liu, Yashu; Zhu, Thant S.; Xie, Xiaolei; Costello, Mark A.; Talsma, Caroline E.; Flack, Callie G.; Crowley, Jessica G.; DiMeco, Francesco; Vescovi, Angelo L.; Fan, Xing; Lubman, David M.

2010-01-01

Cancer stem cells are responsible for tumor formation through self-renewal and differentiation into multiple cell types, and thus represent a new therapeutic target for tumors. Glycoproteins play a critical role in determining the fates of stem cells such as self-renewal, proliferation and differentiation. Here we applied a multi-lectin affinity chromatography and quantitative glycoproteomics approach to analyze alterations of glycoproteins relevant to the differentiation of a glioblastoma-derived stem cell line HSR-GBM1. Three lectins including concanavalin A (Con A), wheat germ agglutinin (WGA) and peanut agglutinin (PNA) were used to capture glycoproteins, followed by LC-MS/MS analysis. A total of 73 and 79 high-confidence (FDR < 0.01) glycoproteins were identified from the undifferentiated and differentiated cells, respectively. Label-free quantitation resulted in the discovery of 18 differentially expressed glycoproteins, wherein 9 proteins are localized in the lysosome. All of these lysosomal glycoproteins were up-regulated after differentiation, where their principal function was hydrolysis of glycosyl residues. Protein-protein interaction and functional analyses revealed the active involvement of lysosomes during the process of glioblastoma stem cell differentiation. This work provides glycoprotein markers to characterize differentiation status of glioblastoma stem cells which may be useful in stemcell therapy of glioblastoma. PMID:21110520

Specific TRPC6 Channel Activation, a Novel Approach to Stimulate Keratinocyte Differentiation*S⃞

PubMed Central

Müller, Margarethe; Essin, Kirill; Hill, Kerstin; Beschmann, Heike; Rubant, Simone; Schempp, Christoph M.; Gollasch, Maik; Boehncke, W. Henning; Harteneck, Christian; Müller, Walter E.; Leuner, Kristina

2008-01-01

The protective epithelial barrier in our skin undergoes constant regulation, whereby the balance between differentiation and proliferation of keratinocytes plays a major role. Impaired keratinocyte differentiation and proliferation are key elements in the pathophysiology of several important dermatological diseases, including atopic dermatitis and psoriasis. Ca2+ influx plays an essential role in this process presumably mediated by different transient receptor potential (TRP) channels. However, investigating their individual role was hampered by the lack of specific stimulators or inhibitors. Because we have recently identified hyperforin as a specific TRPC6 activator, we investigated the contribution of TRPC6 to keratinocyte differentiation and proliferation. Like the endogenous differentiation stimulus high extracellular Ca2+ concentration ([Ca2+]o), hyperforin triggers differentiation in HaCaT cells and in primary cultures of human keratinocytes by inducing Ca2+ influx via TRPC6 channels and additional inhibition of proliferation. Knocking down TRPC6 channels prevents the induction of Ca2+- and hyperforin-induced differentiation. Importantly, TRPC6 activation is sufficient to induce keratinocyte differentiation similar to the physiological stimulus [Ca2+]o. Therefore, TRPC6 activation by hyperforin may represent a new innovative therapeutic strategy in skin disorders characterized by altered keratinocyte differentiation. PMID:18818211

Multi-voxel Patterns Reveal Functionally Differentiated Networks Underlying Auditory Feedback Processing of Speech

PubMed Central

Zheng, Zane Z.; Vicente-Grabovetsky, Alejandro; MacDonald, Ewen N.; Munhall, Kevin G.; Cusack, Rhodri; Johnsrude, Ingrid S.

2013-01-01

The everyday act of speaking involves the complex processes of speech motor control. An important component of control is monitoring, detection and processing of errors when auditory feedback does not correspond to the intended motor gesture. Here we show, using fMRI and converging operations within a multi-voxel pattern analysis framework, that this sensorimotor process is supported by functionally differentiated brain networks. During scanning, a real-time speech-tracking system was employed to deliver two acoustically different types of distorted auditory feedback or unaltered feedback while human participants were vocalizing monosyllabic words, and to present the same auditory stimuli while participants were passively listening. Whole-brain analysis of neural-pattern similarity revealed three functional networks that were differentially sensitive to distorted auditory feedback during vocalization, compared to during passive listening. One network of regions appears to encode an ‘error signal’ irrespective of acoustic features of the error: this network, including right angular gyrus, right supplementary motor area, and bilateral cerebellum, yielded consistent neural patterns across acoustically different, distorted feedback types, only during articulation (not during passive listening). In contrast, a fronto-temporal network appears sensitive to the speech features of auditory stimuli during passive listening; this preference for speech features was diminished when the same stimuli were presented as auditory concomitants of vocalization. A third network, showing a distinct functional pattern from the other two, appears to capture aspects of both neural response profiles. Taken together, our findings suggest that auditory feedback processing during speech motor control may rely on multiple, interactive, functionally differentiated neural systems. PMID:23467350

Altered miRNA processing disrupts brown/white adipocyte determination and associates with lipodystrophy

PubMed Central

Mori, Marcelo A.; Thomou, Thomas; Boucher, Jeremie; Lee, Kevin Y.; Lallukka, Susanna; Kim, Jason K.; Torriani, Martin; Yki-Järvinen, Hannele; Grinspoon, Steven K.; Cypess, Aaron M.; Kahn, C. Ronald

2014-01-01

miRNAs are important regulators of biological processes in many tissues, including the differentiation and function of brown and white adipocytes. The endoribonuclease dicer is a major component of the miRNA-processing pathway, and in adipose tissue, levels of dicer have been shown to decrease with age, increase with caloric restriction, and influence stress resistance. Here, we demonstrated that mice with a fat-specific KO of dicer develop a form of lipodystrophy that is characterized by loss of intra-abdominal and subcutaneous white fat, severe insulin resistance, and enlargement and “whitening” of interscapular brown fat. Additionally, KO of dicer in cultured brown preadipocytes promoted a white adipocyte–like phenotype and reduced expression of several miRNAs. Brown preadipocyte whitening was partially reversed by expression of miR-365, a miRNA known to promote brown fat differentiation; however, introduction of other miRNAs, including miR-346 and miR-362, also contributed to reversal of the loss of the dicer phenotype. Interestingly, fat samples from patients with HIV-related lipodystrophy exhibited a substantial downregulation of dicer mRNA expression. Together, these findings indicate the importance of miRNA processing in white and brown adipose tissue determination and provide a potential link between this process and HIV-related lipodystrophy. PMID:24983316

Temporal Profiling and Pulsed SILAC Labeling Identify Novel Secreted Proteins During Ex Vivo Osteoblast Differentiation of Human Stromal Stem Cells*

PubMed Central

Kristensen, Lars P.; Chen, Li; Nielsen, Maria Overbeck; Qanie, Diyako W.; Kratchmarova, Irina; Kassem, Moustapha; Andersen, Jens S.

2012-01-01

It is well established that bone forming cells (osteoblasts) secrete proteins with autocrine, paracrine, and endocrine function. However, the identity and functional role for the majority of these secreted and differentially expressed proteins during the osteoblast (OB) differentiation process, is not fully established. To address these questions, we quantified the temporal dynamics of the human stromal (mesenchymal, skeletal) stem cell (hMSC) secretome during ex vivo OB differentiation using stable isotope labeling by amino acids in cell culture (SILAC). In addition, we employed pulsed SILAC labeling to distinguish genuine secreted proteins from intracellular contaminants. We identified 466 potentially secreted proteins that were quantified at 5 time-points during 14-days ex vivo OB differentiation including 41 proteins known to be involved in OB functions. Among these, 315 proteins exhibited more than 2-fold up or down-regulation. The pulsed SILAC method revealed a strong correlation between the fraction of isotope labeling and the subset of proteins known to be secreted and involved in OB differentiation. We verified SILAC data using qRT-PCR analysis of 9 identified potential novel regulators of OB differentiation. Furthermore, we studied the biological effects of one of these proteins, the hormone stanniocalcin 2 (STC2) and demonstrated its autocrine effects in enhancing osteoblastic differentiation of hMSC. In conclusion, combining complete and pulsed SILAC labeling facilitated the identification of novel factors produced by hMSC with potential role in OB differentiation. Our study demonstrates that the secretome of osteoblastic cells is more complex than previously reported and supports the emerging evidence that osteoblastic cells secrete proteins with endocrine functions and regulate cellular processes beyond bone formation. PMID:22801418

Theoretical Studies in Chemical Kinetics - Annual Report, 1970.

DOE R&D Accomplishments Database

Karplus, Martin

1970-10-01

The research performed includes (a) Alkali-Halide, Alkali-Halide (MX, M?X?) Exchange Reactions; (b) Inversion Problem; (c) Quantum Mechanics of Scattering Processes, (d) Transition State Analysis of Classical Trajectories, (e) Differential Cross Sections from Classical Trajectories; and (f) Other Studies.

Berry Flesh and Skin Ripening Features in Vitis vinifera as Assessed by Transcriptional Profiling

PubMed Central

Grimplet, Jérôme; Bravo, Gema; Flores, Pilar; Fenoll, José; Hellín, Pilar; Oliveros, Juan Carlos; Martínez-Zapater, José M.

2012-01-01

Background Ripening of fleshy fruit is a complex developmental process involving the differentiation of tissues with separate functions. During grapevine berry ripening important processes contributing to table and wine grape quality take place, some of them flesh- or skin-specific. In this study, transcriptional profiles throughout flesh and skin ripening were followed during two different seasons in a table grape cultivar ‘Muscat Hamburg’ to determine tissue-specific as well as common developmental programs. Methodology/Principal Findings Using an updated GrapeGen Affymetrix GeneChip® annotation based on grapevine 12×v1 gene predictions, 2188 differentially accumulated transcripts between flesh and skin and 2839 transcripts differentially accumulated throughout ripening in the same manner in both tissues were identified. Transcriptional profiles were dominated by changes at the beginning of veraison which affect both pericarp tissues, although frequently delayed or with lower intensity in the skin than in the flesh. Functional enrichment analysis identified the decay on biosynthetic processes, photosynthesis and transport as a major part of the program delayed in the skin. In addition, a higher number of functional categories, including several related to macromolecule transport and phenylpropanoid and lipid biosynthesis, were over-represented in transcripts accumulated to higher levels in the skin. Functional enrichment also indicated auxin, gibberellins and bHLH transcription factors to take part in the regulation of pre-veraison processes in the pericarp, whereas WRKY and C2H2 family transcription factors seems to more specifically participate in the regulation of skin and flesh ripening, respectively. Conclusions/Significance A transcriptomic analysis indicates that a large part of the ripening program is shared by both pericarp tissues despite some components are delayed in the skin. In addition, important tissue differences are present from early stages prior to the ripening onset including tissue-specific regulators. Altogether, these findings provide key elements to understand berry ripening and its differential regulation in flesh and skin. PMID:22768087

Cysteine proteases and cell differentiation: excystment of the ciliated protist Sterkiella histriomuscorum.

PubMed

Villalobo, Eduardo; Moch, Clara; Fryd-Versavel, Ghislaine; Fleury-Aubusson, Anne; Morin, Loïc

2003-12-01

The process of excystment of Sterkiella histriomuscorum (Ciliophora, Oxytrichidae) leads in a few hours, through a massive influx of water and the resorption of the cyst wall, from an undifferentiated resting cyst to a highly differentiated and dividing vegetative cell. While studying the nature of the genes involved in this process, we isolated three different cysteine proteases genes, namely, a cathepsin B gene, a cathepsin L-like gene, and a calpain-like gene. Excystation was selectively inhibited at a precise differentiating stage by cysteine proteases inhibitors, suggesting that these proteins are specifically required during the excystment process. Reverse transcription-PCR experiments showed that both genes display differential expression between the cyst and the vegetative cells. A phylogenetic analysis showed for the first time that the cathepsin B tree is paraphyletic and that the diverging S. histriomuscorum cathepsin B is closely related to its Giardia homologues, which take part in the cyst wall breakdown process. The deduced cathepsin L-like protein sequence displays the structural signatures and phylogenetic relationships of cathepsin H, a protein that is known only in plants and animals and that is involved in the degradation of extracellular matrix components in cancer diseases. The deduced calpain-like protein sequence does not display the calcium-binding domain of conventional calpains; it belongs to a diverging phylogenetic cluster that includes Aspergillus palB, a protein which is involved in a signal transduction pathway that is sensitive to ambient pH.

New insights into the mechanisms of acetic acid resistance in Acetobacter pasteurianus using iTRAQ-dependent quantitative proteomic analysis.

PubMed

Xia, Kai; Zang, Ning; Zhang, Junmei; Zhang, Hong; Li, Yudong; Liu, Ye; Feng, Wei; Liang, Xinle

2016-12-05

Acetobacter pasteurianus is the main starter in rice vinegar manufacturing due to its remarkable abilities to resist and produce acetic acid. Although several mechanisms of acetic acid resistance have been proposed and only a few effector proteins have been identified, a comprehensive depiction of the biological processes involved in acetic acid resistance is needed. In this study, iTRAQ-based quantitative proteomic analysis was adopted to investigate the whole proteome of different acidic titers (3.6, 7.1 and 9.3%, w/v) of Acetobacter pasteurianus Ab3 during the vinegar fermentation process. Consequently, 1386 proteins, including 318 differentially expressed proteins (p<0.05), were identified. Compared to that in the low titer circumstance, cells conducted distinct biological processes under high acetic acid stress, where >150 proteins were differentially expressed. Specifically, proteins involved in amino acid metabolic processes and fatty acid biosynthesis were differentially expressed, which may contribute to the acetic acid resistance of Acetobacter. Transcription factors, two component systems and toxin-antitoxin systems were implicated in the modulatory network at multiple levels. In addition, the identification of proteins involved in redox homeostasis, protein metabolism, and the cell envelope suggested that the whole cellular system is mobilized in response to acid stress. These findings provide a differential proteomic profile of acetic acid resistance in Acetobacter pasteurianus and have potential application to highly acidic rice vinegar manufacturing. Copyright © 2016 Elsevier B.V. All rights reserved.

A well-refined in vitro model derived from human embryonic stem cell for screening phytochemicals with midbrain dopaminergic differentiation-boosting potential for improving Parkinson's disease.

PubMed

Hsieh, Wen-Ting; Chiang, Been-Huang

2014-07-09

Stimulation of endogenous neurogenesis is a potential approach to compensate for loss of dopaminergic neurons of substantia nigra compacta nigra (SNpc) in patients with Parkinson's disease (PD). This objective was to establish an in vitro model by differentiating pluripotent human embryonic stem cells (hESCs) into midbrain dopaminergic (mDA) neurons for screening phytochemicals with mDA neurogenesis-boosting potentials. Consequently, a five-stage differentiation process was developed. The derived cells expressed many mDA markers including tyrosine hydroxylase (TH), β-III tubulin, and dopamine transporter (DAT). The voltage-gated ion channels and dopamine release were also examined for verifying neuron function, and the dopamine receptor agonists bromocriptine and 7-hydroxy-2-(dipropylamino)tetralin (7-OH-DPAT) were used to validate our model. Then, several potential phytochemicals including green tea catechins and ginsenosides were tested using the model. Finally, ginsenoside Rb1 was identified as the most potent phytochemical which is capable of upregulating neurotrophin expression and inducing mDA differentiation.

Both endo-siRNAs and tRNA-derived small RNAs are involved in the differentiation of primitive eukaryote Giardia lamblia

PubMed Central

Liao, Jian-You; Guo, Yan-Hua; Zheng, Ling-Ling; Li, Yan; Xu, Wen-Li; Zhang, Yu-Chan; Zhou, Hui; Lun, Zhao-Rong; Ayala, Francisco J.; Qu, Liang-Hu

2014-01-01

Small RNAs (sRNAs), including microRNAs and endogenous siRNAs (endo-siRNAs), regulate most important biologic processes in eukaryotes, such as cell division and differentiation. Although sRNAs have been extensively studied in various eukaryotes, the role of sRNAs in the early emergence of eukaryotes is unclear. To address these questions, we deep sequenced the sRNA transcriptome of four different stages in the differentiation of Giardia lamblia, one of the most primitive eukaryotes. We identified a large number of endo-siRNAs in this fascinating parasitic protozoan and found that they were produced from live telomeric retrotransposons and three genomic regions (i.e., endo-siRNA generating regions [eSGRs]). eSGR-derived endo-siRNAs were proven to target mRNAs in trans. Gradual up-regulation of endo-siRNAs in the differentiation of Giardia suggested that they might be involved in the regulation of this process. This hypothesis was supported by the impairment of the differentiation ability of Giardia when GLDICER, essential for the biogenesis of endo-siRNAs, was knocked down. Endo-siRNAs are not the only sRNA regulators in Giardia differentiation, because a great number of tRNAs-derived sRNAs showed more dramatic expression changes than endo-siRNAs in this process. We totally identified five novel kinds of tRNAs-derived sRNAs and found that the biogenesis in four of them might be correlated with that of stress-induced tRNA-derived RNA (sitRNA), which was discovered in our previous studies. Our studies reveal an unexpected complex panorama of sRNA in G. lamblia and shed light on the origin and functional evolution of eukaryotic sRNAs. PMID:25225396

Stem Cell Differentiation Stage Factors and Their Role in Triggering Symmetry Breaking Processes during Cancer Development: A Quantum Field Theory Model for Reprogramming Cancer Cells to Healthy Phenotypes.

PubMed

Biava, Pier Mario; Burigana, Fabio; Germano, Roberto; Kurian, Philip; Verzegnassi, Claudio; Vitiello, Giuseppe

2017-09-20

A long history of research has pursued the use of embryonic factors isolated during cell differentiation processes for the express purpose of transforming cancer cells back to healthy phenotypes. Recent results have clarified that the substances present at different stages of cell differentiation-which we call stem cell differentiation stage factors (SCDSFs)-are proteins with low molecular weight and nucleic acids that regulate genomic expression. The present review summarizes how these substances, taken at different stages of cellular maturation, are able to retard proliferation of many human tumor cell lines and thereby reprogram cancer cells to healthy phenotypes. The model presented here is a quantum field theory (QFT) model in which SCDSFs are able to trigger symmetry breaking processes during cancer development. These symmetry breaking processes, which lie at the root of many phenomena in elementary particle physics and condensed matter physics, govern the phase transitions of totipotent cells to higher degrees of diversity and order, resulting in cell differentiation. In cancers, which share many genomic and metabolic similarities with embryonic stem cells, stimulated re-differentiation often signifies the phenotypic reversion back to health and non-proliferation. In addition to acting on key components of the cellular cycle, SCDSFs are able to reprogram cancer cells by delicately influencing the cancer microenvironment, modulating the electrochemistry and thus the collective electrodynamic behaviors between dipole networks in biomacromolecules and the interstitial water field. Coherent effects in biological water, which are derived from a dissipative QFT framework, may offer new diagnostic and therapeutic targets at a systemic level, before tumor instantiation occurs in specific tissues or organs. Thus, by including the environment as an essential component of our model, we may push the prevailing paradigm of mutation-driven oncogenesis toward a closer description of reality. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A comprehensive evaluation of popular proteomics software workflows for label-free proteome quantification and imputation.

PubMed

Välikangas, Tommi; Suomi, Tomi; Elo, Laura L

2017-05-31

Label-free mass spectrometry (MS) has developed into an important tool applied in various fields of biological and life sciences. Several software exist to process the raw MS data into quantified protein abundances, including open source and commercial solutions. Each software includes a set of unique algorithms for different tasks of the MS data processing workflow. While many of these algorithms have been compared separately, a thorough and systematic evaluation of their overall performance is missing. Moreover, systematic information is lacking about the amount of missing values produced by the different proteomics software and the capabilities of different data imputation methods to account for them.In this study, we evaluated the performance of five popular quantitative label-free proteomics software workflows using four different spike-in data sets. Our extensive testing included the number of proteins quantified and the number of missing values produced by each workflow, the accuracy of detecting differential expression and logarithmic fold change and the effect of different imputation and filtering methods on the differential expression results. We found that the Progenesis software performed consistently well in the differential expression analysis and produced few missing values. The missing values produced by the other software decreased their performance, but this difference could be mitigated using proper data filtering or imputation methods. Among the imputation methods, we found that the local least squares (lls) regression imputation consistently increased the performance of the software in the differential expression analysis, and a combination of both data filtering and local least squares imputation increased performance the most in the tested data sets. © The Author 2017. Published by Oxford University Press.

Microarray analysis of gene expression alteration in human middle ear epithelial cells induced by micro particle.

PubMed

Song, Jae-Jun; Kwon, Jee Young; Park, Moo Kyun; Seo, Young Rok

2013-10-01

The primary aim of this study is to reveal the effect of particulate matter (PM) on the human middle ear epithelial cell (HMEEC). The HMEEC was treated with PM (300 μg/ml) for 24 h. Total RNA was extracted and used for microarray analysis. Molecular pathways among differentially expressed genes were further analyzed by using Pathway Studio 9.0 software. For selected genes, the changes in gene expression were confirmed by real-time PCR. A total of 611 genes were regulated by PM. Among them, 366 genes were up-regulated, whereas 245 genes were down-regulated. Up-regulated genes were mainly involved in cellular processes, including reactive oxygen species generation, cell proliferation, apoptosis, cell differentiation, inflammatory response and immune response. Down-regulated genes affected several cellular processes, including cell differentiation, cell cycle, proliferation, apoptosis and cell migration. A total of 21 genes were discovered as crucial components in potential signaling networks containing 2-fold up regulated genes. Four genes, VEGFA, IL1B, CSF2 and HMOX1 were revealed as key mediator genes among the up-regulated genes. A total of 25 genes were revealed as key modulators in the signaling pathway associated with 2-fold down regulated genes. Four genes, including IGF1R, TIMP1, IL6 and FN1, were identified as the main modulator genes. We identified the differentially expressed genes in PM-treated HMEEC, whose expression profile may provide a useful clue for the understanding of environmental pathophysiology of otitis media. Our work indicates that air pollution, like PM, plays an important role in the pathogenesis of otitis media. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Domestication drive the changes of immune and digestive system of Eurasian perch (Perca fluviatilis).

PubMed

Chen, Xiaowen; Wang, Jun; Qian, Long; Gaughan, Sarah; Xiang, Wei; Ai, Tao; Fan, Zhenming; Wang, Chenghui

2017-01-01

Domestication has altered a variety of traits within the Eurasian perch (Perca fluviatilis), including phenotypic, physiological and behavioral traits of Eurasian perch (Perca fluviatilis). Little is known, however, about the genetic changes between domesticated and wild Eurasian perch. In this study, we assembled a high-quality de novo reference transcriptome and identified differentially expressed genes between wild and domesticated Eurasian perch. A total of 113,709 transcripts were assembled, and 58,380 transcripts were annotated. Transcriptomic comparison revealed 630 differentially expressed genes between domesticated and wild Eurasian perch. Within domesticated Eurasian perch there were 412 genes that were up-regulated including MHCI, MHCII, chia, ighm within immune system development. There were 218 genes including try1, ctrl, ctrb, cela3b, cpa1 and cpb1, which were down-regulated that were associated with digestive processes. Our results indicated domestication drives the changes of immune and digestive system of Eurasian perch. Our study not only provide valuable genetic resources for further studies in Eurasian perch, but also provide novel insights into the genetic basis of physiological changes in Eurasian perch during domestication process.

Domestication drive the changes of immune and digestive system of Eurasian perch (Perca fluviatilis)

PubMed Central

Chen, Xiaowen; Wang, Jun; Qian, Long; Gaughan, Sarah; Xiang, Wei; Ai, Tao; Fan, Zhenming; Wang, Chenghui

2017-01-01

Domestication has altered a variety of traits within the Eurasian perch (Perca fluviatilis), including phenotypic, physiological and behavioral traits of Eurasian perch (Perca fluviatilis). Little is known, however, about the genetic changes between domesticated and wild Eurasian perch. In this study, we assembled a high-quality de novo reference transcriptome and identified differentially expressed genes between wild and domesticated Eurasian perch. A total of 113,709 transcripts were assembled, and 58,380 transcripts were annotated. Transcriptomic comparison revealed 630 differentially expressed genes between domesticated and wild Eurasian perch. Within domesticated Eurasian perch there were 412 genes that were up-regulated including MHCI, MHCII, chia, ighm within immune system development. There were 218 genes including try1, ctrl, ctrb, cela3b, cpa1 and cpb1, which were down-regulated that were associated with digestive processes. Our results indicated domestication drives the changes of immune and digestive system of Eurasian perch. Our study not only provide valuable genetic resources for further studies in Eurasian perch, but also provide novel insights into the genetic basis of physiological changes in Eurasian perch during domestication process. PMID:28257494

Neural correlates of processing facial identity based on features versus their spacing.

PubMed

Maurer, D; O'Craven, K M; Le Grand, R; Mondloch, C J; Springer, M V; Lewis, T L; Grady, C L

2007-04-08

Adults' expertise in recognizing facial identity involves encoding subtle differences among faces in the shape of individual facial features (featural processing) and in the spacing among features (a type of configural processing called sensitivity to second-order relations). We used fMRI to investigate the neural mechanisms that differentiate these two types of processing. Participants made same/different judgments about pairs of faces that differed only in the shape of the eyes and mouth, with minimal differences in spacing (featural blocks), or pairs of faces that had identical features but differed in the positions of those features (spacing blocks). From a localizer scan with faces, objects, and houses, we identified regions with comparatively more activity for faces, including the fusiform face area (FFA) in the right fusiform gyrus, other extrastriate regions, and prefrontal cortices. Contrasts between the featural and spacing conditions revealed distributed patterns of activity differentiating the two conditions. A region of the right fusiform gyrus (near but not overlapping the localized FFA) showed greater activity during the spacing task, along with multiple areas of right frontal cortex, whereas left prefrontal activity increased for featural processing. These patterns of activity were not related to differences in performance between the two tasks. The results indicate that the processing of facial features is distinct from the processing of second-order relations in faces, and that these functions are mediated by separate and lateralized networks involving the right fusiform gyrus, although the FFA as defined from a localizer scan is not differentially involved.

Reading, Comprehension, and Memory Processes: Abstracts of Doctoral Dissertations Published in "Dissertation Abstracts International," July through December 1980 (Vol. 41 Nos. 1 through 6).

ERIC Educational Resources Information Center

ERIC Clearinghouse on Reading and Communication Skills, Urbana, IL.

This collection of abstracts is part of a continuing series providing information on recent doctoral dissertations. The 31 titles deal with a variety of topics, including the following: (1) teaching strategies for reading comprehension; (2) strategies for assigning meaning to unfamiliar words in context; (3) differential processing of explicit and…

Annual Review of Sociology. Volume 9, 1983.

ERIC Educational Resources Information Center

Turner, Ralph H., Ed.; Short, James F., Jr., Ed.

Twenty-six essays describing current research in sociology are included in this publication. The essays fall into 10 categories: differentiation and stratification; political sociology; social processes; institutions; individual and society; formal organizations; urban sociology; theory and methods; sociology of world regions; and historical…

Neural Differentiation of Embryonic Stem Cells In Vitro: A Road Map to Neurogenesis in the Embryo

PubMed Central

Abranches, Elsa; Silva, Margarida; Pradier, Laurent; Schulz, Herbert; Hummel, Oliver; Henrique, Domingos; Bekman, Evguenia

2009-01-01

Background The in vitro generation of neurons from embryonic stem (ES) cells is a promising approach to produce cells suitable for neural tissue repair and cell-based replacement therapies of the nervous system. Available methods to promote ES cell differentiation towards neural lineages attempt to replicate, in different ways, the multistep process of embryonic neural development. However, to achieve this aim in an efficient and reproducible way, a better knowledge of the cellular and molecular events that are involved in the process, from the initial specification of neuroepithelial progenitors to their terminal differentiation into neurons and glial cells, is required. Methodology/Principal Findings In this work, we characterize the main stages and transitions that occur when ES cells are driven into a neural fate, using an adherent monolayer culture system. We established improved conditions to routinely produce highly homogeneous cultures of neuroepithelial progenitors, which organize into neural tube-like rosettes when they acquire competence for neuronal production. Within rosettes, neuroepithelial progenitors display morphological and functional characteristics of their embryonic counterparts, namely, apico-basal polarity, active Notch signalling, and proper timing of production of neurons and glia. In order to characterize the global gene activity correlated with each particular stage of neural development, the full transcriptome of different cell populations that arise during the in vitro differentiation protocol was determined by microarray analysis. By using embryo-oriented criteria to cluster the differentially expressed genes, we define five gene expression signatures that correlate with successive stages in the path from ES cells to neurons. These include a gene signature for a primitive ectoderm-like stage that appears after ES cells enter differentiation, and three gene signatures for subsequent stages of neural progenitor development, from an early stage that follows neural induction to a final stage preceding terminal differentiation. Conclusions/Significance Overall, our work confirms and extends the cellular and molecular parallels between monolayer ES cell neural differentiation and embryonic neural development, revealing in addition novel aspects of the genetic network underlying the multistep process that leads from uncommitted cells to differentiated neurons. PMID:19621087

Bioinformatic analysis of the effects and mechanisms of decitabine and cytarabine on acute myeloid leukemia

PubMed Central

Zhou, Shiyong; Liu, Pengfei; Zhang, Huilai

2017-01-01

Acute myeloid leukemia (AML) is a frequently occurring malignant disease of the blood and may result from a variety of genetic disorders. The present study aimed to identify the underlying mechanisms associated with the therapeutic effects of decitabine and cytarabine on AML, using microarray analysis. The microarray datasets GSE40442 and GSE40870 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially methylated sites were identified in AML cells treated with decitabine compared with those treated with cytarabine via the Linear Models for Microarray Data package, following data pre-processing. Gene Ontology (GO) analysis of DEGs was performed using the Database for Annotation, Visualization and Integrated Analysis Discovery. Genes corresponding to the differentially methylated sites were obtained using the annotation package of the methylation microarray platform. The overlapping genes were identified, which exhibited the opposite variation trend between gene expression and DNA methylation. Important transcription factor (TF)-gene pairs were screened out, and a regulated network subsequently constructed. A total of 190 DEGs and 540 differentially methylated sites were identified in AML cells treated with decitabine compared with those treated with cytarabine. A total of 36 GO terms of DEGs were enriched, including nucleosomes, protein-DNA complexes and the nucleosome assembly. The 540 differentially methylated sites were located on 240 genes, including the acid-repeat containing protein (ACRC) gene that was additionally differentially expressed. In addition, 60 TF pairs and overlapped methylated sites, and 140 TF-pairs and DEGs were screened out. The regulated network included 68 nodes and 140 TF-gene pairs. The present study identified various genes including ACRC and proliferating cell nuclear antigen, in addition to various TFs, including TATA-box binding protein associated factor 1 and CCCTC-binding factor, which may be potential therapeutic targets of AML. PMID:28498449

Bioinformatic analysis of the effects and mechanisms of decitabine and cytarabine on acute myeloid leukemia.

PubMed

Zhou, Shiyong; Liu, Pengfei; Zhang, Huilai

2017-07-01

Acute myeloid leukemia (AML) is a frequently occurring malignant disease of the blood and may result from a variety of genetic disorders. The present study aimed to identify the underlying mechanisms associated with the therapeutic effects of decitabine and cytarabine on AML, using microarray analysis. The microarray datasets GSE40442 and GSE40870 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially methylated sites were identified in AML cells treated with decitabine compared with those treated with cytarabine via the Linear Models for Microarray Data package, following data pre‑processing. Gene Ontology (GO) analysis of DEGs was performed using the Database for Annotation, Visualization and Integrated Analysis Discovery. Genes corresponding to the differentially methylated sites were obtained using the annotation package of the methylation microarray platform. The overlapping genes were identified, which exhibited the opposite variation trend between gene expression and DNA methylation. Important transcription factor (TF)‑gene pairs were screened out, and a regulated network subsequently constructed. A total of 190 DEGs and 540 differentially methylated sites were identified in AML cells treated with decitabine compared with those treated with cytarabine. A total of 36 GO terms of DEGs were enriched, including nucleosomes, protein‑DNA complexes and the nucleosome assembly. The 540 differentially methylated sites were located on 240 genes, including the acid‑repeat containing protein (ACRC) gene that was additionally differentially expressed. In addition, 60 TF pairs and overlapped methylated sites, and 140 TF‑pairs and DEGs were screened out. The regulated network included 68 nodes and 140 TF‑gene pairs. The present study identified various genes including ACRC and proliferating cell nuclear antigen, in addition to various TFs, including TATA‑box binding protein associated factor 1 and CCCTC‑binding factor, which may be potential therapeutic targets of AML.

Measurements of Heavy Ion Differential Streaming with SOHO/CELIAS/CTOF and ACE/SWICS at 1 AU

NASA Astrophysics Data System (ADS)

Janitzek, Nils; Berger, Lars; Taut, Andreas; Drews, Christian; Wimmer-Schweingruber, Robert

2016-04-01

Helios measurements in the early 1980s showed the existence of a systematic velocity difference, called "differential streaming", between solar wind bulk protons and alpha particles with the alphas streaming faster than the protons. The absolute differential speed between these species decreases with radial distance to the Sun and decreasing proton speed. In the fast wind it was measured to be approximately half of the local Alfvén speed. However, the detailed processes of acceleration and regulation of differential streaming are still not well understood. A proposed key process is resonant wave particle interaction between the ions and Alfvén waves near the ion-cyclotron frequency which is able to accelerate the alphas preferentially due to their higher mass-per-charge ratio. Measuring the differential speed of a wide set of solar wind heavy ions and therefore extending the mass-per-charge range significantly can provide additional information on the underlying processes that we cannot infer from the alphas and protons alone. We analysed data measured at L1 by SOHO/CELIAS/CTOF in 1996 and ACE/SWICS from 2001 to 2010. Both instruments are linear time-of-flight mass spectrometers which measure the ions' radial 1D velocity distributions with a cadence of 5 and 12 minutes, respectively. Comparing the mean ion speed, with the mean proton speed measured routinely by the SOHO/CELIAS/MTOF/PM and ACE/SWEPAM, respectively, we obtain the differential streaming for major charge states of solar wind carbon, oxygen, neon, magnesium, silicon and iron. In the case of the SWICS data the magnetometer on-board ACE (ACE/MAG) allows us to directly relate the differential streaming to the ambient Alfvén velocity while the lack of in-situ magnetic field measurements on SOHO is compensated by a B-field extrapolation from the WIND spacecraft (WIND/MAG) to the SOHO site. Both instruments show a similar result: significant differential streaming between heavy ions and protons on the order of the local Alfvén speed for solar wind above 400 km/s. While for slow solar wind the picture is more complex, the differential streaming is ubiquitous in the fast wind. Neither of the instruments measured a clear trend with ion mass-per-charge as would be expected from simple models including ion cyclotron resonance as the main driving process. Finally, we discuss a possible dependence of the differential streaming on the solar cycle.

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)

Identification of differentially expressed proteins in Ostrinia furnacalis adults after exposure to ultraviolet A.

PubMed

Zhang, Changyu; Meng, Jianyu

2018-06-23

Ultraviolet A (UVA), the major component of solar UV irradiation, is an important environmental factor inducing damage to insects including cell death, photoreceptor damage, and oxidative stress. In order to improve understanding of the adaptation mechanisms of insect after UVA exposure, a comparative proteomic analysis was carried out to reveal differential protein expression in Ostrinia furnacalis. Three-day-old adults were treated with UVA for 1 h. Total proteins of control and UVA-treated insects were examined using two-dimensional electrophoresis (2-DE). 2-DE analysis demonstrated that 19 proteins were increased and 18 proteins were decreased significantly in O. furnacalis after UVA exposure, respectively. Thirty differentially expressed proteins were successfully identified by mass spectrometry. The identified proteins were involved in diverse biological processes, such as signal transduction, transport processing, cellular stress, metabolisms, and cytoskeleton organization. Our results reveal that the response patterns of O. furnacalis to UVA irradiation are complex and provide novel insights into the adaptation response to UVA irradiation stress.

Lepton Number Violating e-W+ → e+W- → W-W- Processes in the Left-Right Gauge Model

NASA Astrophysics Data System (ADS)

Doi, M.

1999-03-01

As new tests of the nature of neutrinos, lepton number violating e-W+a → e+W-b and e-e- → W-a W-b processes are studied within the SU(2)L × SU(2)R × U(1)B-L gauge model. They take place via exchange of a Majorana neutrino and a doubly charged Higgs particle. Differential cross sections are derived in the most general form. The angular distribution of the former process becomes resonant at cos θj= -1+2(Ma2Mb2 -mj2s)/ (s-Ma2) (s-Mb2), from which the neutrino mass mj can be deduced. Differential cross sections are estimated by using present bounds on the parameters. The cross section of the former process is about 102 times larger than the latter. Another process, e-p → e+W-n, which includes e-W+ → e+ W- as a sub-process, is also discussed, and orders of magnitude of the cross section are estimated.

Confocal Analysis of Nuclear Lamina Behavior during Male Meiosis and Spermatogenesis in Drosophila melanogaster.

PubMed

Fabbretti, Fabiana; Iannetti, Ilaria; Guglielmi, Loredana; Perconti, Susanna; Evangelistella, Chiara; Proietti De Santis, Luca; Bongiorni, Silvia; Prantera, Giorgio

2016-01-01

Lamin family proteins are structural components of a filamentous framework, the nuclear lamina (NL), underlying the inner membrane of nuclear envelope. The NL not only plays a role in nucleus mechanical support and nuclear shaping, but is also involved in many cellular processes including DNA replication, gene expression and chromatin positioning. Spermatogenesis is a very complex differentiation process in which each stage is characterized by nuclear architecture dramatic changes, from the early mitotic stage to the sperm differentiation final stage. Nevertheless, very few data are present in the literature on the NL behavior during this process. Here we show the first and complete description of NL behavior during meiosis and spermatogenesis in Drosophila melanogaster. By confocal imaging, we characterized the NL modifications from mitotic stages, through meiotic divisions to sperm differentiation with an anti-laminDm0 antibody against the major component of the Drosophila NL. We observed that continuous changes in the NL structure occurred in parallel with chromatin reorganization throughout the whole process and that meiotic divisions occurred in a closed context. Finally, we analyzed NL in solofuso meiotic mutant, where chromatin segregation is severely affected, and found the strict correlation between the presence of chromatin and that of NL.

Confocal Analysis of Nuclear Lamina Behavior during Male Meiosis and Spermatogenesis in Drosophila melanogaster

PubMed Central

Fabbretti, Fabiana; Iannetti, Ilaria; Guglielmi, Loredana; Perconti, Susanna; Evangelistella, Chiara; Proietti De Santis, Luca; Bongiorni, Silvia; Prantera, Giorgio

2016-01-01

Lamin family proteins are structural components of a filamentous framework, the nuclear lamina (NL), underlying the inner membrane of nuclear envelope. The NL not only plays a role in nucleus mechanical support and nuclear shaping, but is also involved in many cellular processes including DNA replication, gene expression and chromatin positioning. Spermatogenesis is a very complex differentiation process in which each stage is characterized by nuclear architecture dramatic changes, from the early mitotic stage to the sperm differentiation final stage. Nevertheless, very few data are present in the literature on the NL behavior during this process. Here we show the first and complete description of NL behavior during meiosis and spermatogenesis in Drosophila melanogaster. By confocal imaging, we characterized the NL modifications from mitotic stages, through meiotic divisions to sperm differentiation with an anti-laminDm0 antibody against the major component of the Drosophila NL. We observed that continuous changes in the NL structure occurred in parallel with chromatin reorganization throughout the whole process and that meiotic divisions occurred in a closed context. Finally, we analyzed NL in solofuso meiotic mutant, where chromatin segregation is severely affected, and found the strict correlation between the presence of chromatin and that of NL. PMID:26963718

Different roles of TGF-β in the multi-lineage differentiation of stem cells

PubMed Central

Wang, Ming-Ke; Sun, Hui-Qin; Xiang, Ying-Chun; Jiang, Fan; Su, Yong-Ping; Zou, Zhong-Min

2012-01-01

Stem cells are a population of cells that has infinite or long-term self-renewal ability and can produce various kinds of descendent cells. Transforming growth factor β (TGF-β) family is a superfamily of growth factors, including TGF-β1, TGF-β2 and TGF-β3, bone morphogenetic proteins, activin/inhibin, and some other cytokines such as nodal, which plays very important roles in regulating a wide variety of biological processes, such as cell growth, differentiation, cell death. TGF-β, a pleiotropic cytokine, has been proved to be differentially involved in the regulation of multi-lineage differentiation of stem cells, through the Smad pathway, non-Smad pathways including mitogen-activated protein kinase pathways, phosphatidylinositol-3-kinase/AKT pathways and Rho-like GTPase signaling pathways, and their cross-talks. For instance, it is generally known that TGF-β promotes the differentiation of stem cells into smooth muscle cells, immature cardiomyocytes, chondrocytes, neurocytes, hepatic stellate cells, Th17 cells, and dendritic cells. However, TGF-β inhibits the differentiation of stem cells into myotubes, adipocytes, endothelial cells, and natural killer cells. Additionally, TGF-β can provide competence for early stages of osteoblastic differentiation, but at late stages TGF-β acts as an inhibitor. The three mammalian isoforms (TGF-β1, 2 and 3) have distinct but overlapping effects on hematopoiesis. Understanding the mechanisms underlying the regulatory effect of TGF-β in the stem cell multi-lineage differentiation is of importance in stem cell biology, and will facilitate both basic research and clinical applications of stem cells. In this article, we discuss the current status and progress in our understanding of different mechanisms by which TGF-β controls multi-lineage differentiation of stem cells. PMID:22993659

Protein expression profiling in head fragments during planarian regeneration after amputation.

PubMed

Chen, Xiaoguang; Xu, Cunshuan

2015-04-01

Following amputation, a planarian tail fragment can regrow into a complete organism including a well-organized brain within about 2-3 weeks, thus restoring the structure and function to presurgical levels. Despite the enormous potential of these animals for regenerative medicine, our understanding of the exact mechanism of planarian regeneration is incomplete. To better understand the molecular nature of planarian head regeneration, we applied two-dimensional electrophoresis (2-DE)/matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF)/time-of-flight mass spectrometry (TOF MS) technique to analyze the dynamic proteomic expression profiles over the course of 6 to 168 h post-decapitation. This approach identified a total of 141 differentially expressed proteins, 47 of which exhibited exceptionally high fold changes (≥3-fold change). Of these, Rx protein, an important regulator of head and brain development, was considered to be closely related to planarian head regeneration because of its exceptional high expression almost throughout the time course of regeneration process. Functional annotation analysis classified the 141 proteins into eight categories: (1) signaling, (2) Ca(2+) binding and translocation, (3) transcription and translation, (4) cytoskeleton, (5) metabolism, (6) cell protection, (7) tissue differentiation, and (8) cell cycle. Signaling pathway analysis indicated that Wnt1/Ca(2+) signaling pathway was activated during head regeneration. Integrating the analyses of proteome expression profiling, functional annotation, and signaling pathway, amputation-induced head reformation requires some mechanisms to promote cell proliferation and differentiation, including differential regulation of proapoptotic and antiapoptotic proteins, and the regulation of proliferation and differentiation-related proteins. Importantly, Wnt1/Ca(2+) signaling pathway upregulates Rx expression, finally facilitating the differentiation of neoblasts into various cell types. Taken together, our study demonstrated that proteomic analysis approach used by us is a powerful tool in understanding molecular process related to head regeneration of planarian.

ATP synthase promotes germ cell differentiation independent of oxidative phosphorylation

PubMed Central

Teixeira, Felipe K.; Sanchez, Carlos G.; Hurd, Thomas R.; Seifert, Jessica R. K.; Czech, Benjamin; Preall, Jonathan B.; Hannon, Gregory J.; Lehmann, Ruth

2015-01-01

The differentiation of stem cells is a tightly regulated process essential for animal development and tissue homeostasis. Through this process, attainment of new identity and function is achieved by marked changes in cellular properties. Intrinsic cellular mechanisms governing stem cell differentiation remain largely unknown, in part because systematic forward genetic approaches to the problem have not been widely used1,2. Analysing genes required for germline stem cell differentiation in the Drosophila ovary, we find that the mitochondrial ATP synthase plays a critical role in this process. Unexpectedly, the ATP synthesizing function of this complex was not necessary for differentiation, as knockdown of other members of the oxidative phosphorylation system did not disrupt the process. Instead, the ATP synthase acted to promote the maturation of mitochondrial cristae during differentiation through dimerization and specific upregulation of the ATP synthase complex. Taken together, our results suggest that ATP synthase-dependent crista maturation is a key developmental process required for differentiation independent of oxidative phosphorylation. PMID:25915123

Population resequencing reveals candidate genes associated with salinity adaptation of the Pacific oyster Crassostrea gigas.

PubMed

She, Zhicai; Li, Li; Meng, Jie; Jia, Zhen; Que, Huayong; Zhang, Guofan

2018-06-06

The Pacific oyster Crassostrea gigas is an important cultivated shellfish. As a euryhaline species, it has evolved adaptive mechanisms responding to the complex and changeable intertidal environment that it inhabits. To investigate the genetic basis of this salinity adaptation mechanism, we conducted a genome-wide association study using phenotypically differentiated populations (hyposalinity and hypersalinity adaptation populations, and control population), and confirmed our results using an independent population, high-resolution melting, and mRNA expression analysis. For the hyposalinity adaptation, we determined 24 genes, including Cg_CLCN7 (chloride channel protein 7) and Cg_AP1 (apoptosis 1 inhibitor), involved in the ion/water channel and transporter mechanisms, free amino acid and reactive oxygen species metabolism, immune responses, and chemical defence. Three SNPs located on these two genes were significantly differentiated between groups, as was Cg_CLCN7. For the hypersalinity adaptation, the biological process for positive regulating the developmental process was enriched. Enriched gene functions were focused on transcriptional regulation, signal transduction, and cell growth and differentiation, including calmodulin (Cg_CaM) and ficolin-2 (Cg_FCN2). These genes and polymorphisms possibly play an important role in oyster hyposalinity and hypersalinity adaptation. They not only further our understanding of salinity adaptation mechanisms but also provide markers for highly adaptable oyster strains suitable for breeding.

NOVEL MECHANISMS FOR THE VITAMIN D RECEPTOR (VDR) IN THE SKIN AND IN SKIN CANCER

PubMed Central

Bikle, Daniel D.; Oda, Yuko; Tu, Chia-Ling; Jiang, Yan

2014-01-01

The VDR acting with or without its principal ligand 1,25(OH)2D regulates two central processes in the skin, interfollicular epidermal (IFE) differentiation and hair follicle cycling (HFC). Calcium is an important co-regulator with 1,25(OH)2 D at least of epidermal differentiation. Knockout of the calcium sensing receptor (CaSR) in addition to VDR accelerates the development of skin cancer in mice on a low calcium diet. Coactivators such as Mediator 1 (aka DRIP205) and steroid receptor coactivator 3 (SRC3) regulate VDR function at different stages of the differentiation process, with Med1 essential for hair follicle differentiation and early stages of epidermal differentiation and proliferation and SRC3 essential for the latter stages of differentiation including formation of the permeability barrier and innate immunity. The corepressor of VDR, hairless (HR), is essential for hair follicle cycling, although its effect on epidermal differentiation in vivo is minimal. In its regulation of HFC and IFE VDR controls two pathways—wnt/β-catenin and sonic hedgehog (Shh). In the absence of VDR these pathways are overexpressed leading to tumor formation. Whereas VDR binding to β-catenin may block its activation of TCF/LEF1 sites, β-catenin binding to VDR may enhance its activation of VDREs. 1,25(OH)2D promotes but may not be required for these interactions. Suppression of Shh expression by VDR, on the other hand, requires 1,25(OH)2D. The major point of emphasis is that the role of VDR in the skin involves a number of novel mechanisms, both 1,25(OH)2D dependent and independent, that when disrupted interfere with IFE differentiation and HFC, predisposing to cancer formation. PMID:25445917

Simple agarose micro-confinement array and machine-learning-based classification for analyzing the patterned differentiation of mesenchymal stem cells

PubMed Central

Sato, Asako; Vogel, Viola; Tanaka, Yo

2017-01-01

The geometrical confinement of small cell colonies gives differential cues to cells sitting at the periphery versus the core. To utilize this effect, for example to create spatially graded differentiation patterns of human mesenchymal stem cells (hMSCs) in vitro or to investigate underpinning mechanisms, the confinement needs to be robust for extended time periods. To create highly repeatable micro-fabricated structures for cellular patterning and high-throughput data mining, we employed here a simple casting method to fabricate more than 800 adhesive patches confined by agarose micro-walls. In addition, a machine learning based image processing software was developed (open code) to detect the differentiation patterns of the population of hMSCs automatically. Utilizing the agarose walls, the circular patterns of hMSCs were successfully maintained throughout 15 days of cell culture. After staining lipid droplets and alkaline phosphatase as the markers of adipogenic and osteogenic differentiation, respectively, the mega-pixels of RGB color images of hMSCs were processed by the software on a laptop PC within several minutes. The image analysis successfully showed that hMSCs sitting on the more central versus peripheral sections of the adhesive circles showed adipogenic versus osteogenic differentiation as reported previously, indicating the compatibility of patterned agarose walls to conventional microcontact printing. In addition, we found a considerable fraction of undifferentiated cells which are preferentially located at the peripheral part of the adhesive circles, even in differentiation-inducing culture media. In this study, we thus successfully demonstrated a simple framework for analyzing the patterned differentiation of hMSCs in confined microenvironments, which has a range of applications in biology, including stem cell biology. PMID:28380036

Methods for imaging individual cilia in living echinoid embryos.

PubMed

Morris, Robert L; Pope, Hans W; Sholi, Adam N; Williams, Leah M; Ettinger, Chelsea R; Beacham, Gwendolyn M; Shintaku, Tatsushi; Abbott, Zachary D; Doherty, Elyse M

2015-01-01

The embryos of echinoids (sea urchins and sand dollars) serve as excellent models for studying cilia differentiation and stages of the cilia life cycle including ciliogenic initiation, growth, maintenance, and retraction. Early in echinoid development, uniform motile cilia form on all cells simultaneously but then rapidly differentiate into multiple cilia types that differ in morphology, motility, and signaling sensitivity. Metal ion treatments that shift germ layer boundaries and thereby "animalize" or "vegetalize" embryos can be used to enrich for low-abundance cilia types rendering those specialized cilia and the differentiation processes they exhibit much easier to study. The experimental advantages of having robust cilia growth and differentiation is tempered by the challenge of restraining ciliated embryos well enough to view the process of ciliogenesis live. We have developed four observation chambers as modifications of the Kiehart chamber for long-term light microscopic imaging of ciliated echinoid embryos. One of these systems employs paramagnetic beads to render ciliated larvae magnetic so they can be gently and reversibly trapped directly under the objective lens. With this magnetic trapping system, the larva can be positioned and repositioned until they achieve the orientation with the clearest view of any cilia of interest. These methods of gentle embryo restraint allow normal embryo development and the normal ciliogenic cycle and ciliary differentiation processes to continue in direct view. Sequential image series can then be collected and analyzed to quantitatively study the wide spectrum of cilia behaviors and properties that arise in developing echinoid embryos. Copyright © 2015. Published by Elsevier Inc.

Myostatin inhibits myosatellite cell proliferation and consequently activates differentiation: evidence for endocrine-regulated transcript processing.

PubMed

Garikipati, Dilip K; Rodgers, Buel D

2012-10-01

Myostatin is a potent negative regulator of muscle growth in mammals. Despite high structural conservation, functional conservation in nonmammalian species is only assumed. This is particularly true for fish due to the presence of several myostatin paralogs: two in most species and four in salmonids (MSTN-1a, -1b, -2a, and -2b). Rainbow trout are a rich source of primary myosatellite cells as hyperplastic muscle growth occurs even in adult fish. These cells were therefore used to determine myostatin's effects on proliferation whereas our earlier studies reported its effects on quiescent cells. As in mammals, recombinant myostatin suppressed proliferation with no changes in cell morphology. Expression of MSTN-1a was several fold higher than the other paralogs and was autoregulated by myostatin, which also upregulated the expression of key differentiation markers: Myf5, MyoD1, myogenin, and myosin light chain. Thus, myostatin-stimulated cellular growth inhibition activates rather than represses differentiation. IGF-1 stimulated proliferation but had minimal and delayed effects on differentiation and its actions were suppressed by myostatin. However, IGF-1 upregulated MSTN-2a expression and the processing of its transcript, which is normally unprocessed. Myostatin therefore appears to partly mediate IGF-stimulated myosatellite differentiation in rainbow trout. This also occurs in mammals, although the IGF-stimulated processing of MSTN-2a transcripts is highly unique and is indicative of subfunctionalization within the gene family. These studies also suggest that the myokine's actions, including its antagonistic relationship with IGF-1, are conserved and that the salmonid gene family is functionally diverging.

Fate vs choice: the immune system reloaded.

PubMed

Murphy, Kenneth M

2005-01-01

Development can occur by either instructive or stochastic processes. My colleagues and I have studied the contributions of these processes to differentiation of naïve CD4+ T-cells to either a Th1 or Th2 phenotype. Our initial discovery that pathogens in our in vitro priming system led to the development of Th1 cells through the action of interleukin-12 was important evidence of a link between innate and adaptive immunity. Subsequent studies in our laboratory revealed an important role for GATA-3 autoactivation in Th2 development. Other interesting projects that have emerged as a result of our Th cell differentiation studies include understanding the role of the inhibitory immunoreceptor B- and T-lymphocyte attenuator in the immune response, as well as the role of the transcription factor ERM in both T-cells and spermatogenesis. We currently maintain our interests in the Th differentiation field by trying to understand the role of type 1 interferons in Th1 development and the role of alternate promoters for the GATA-3 gene, among other things, but are also actively embarking on studies related to the choice between divergent cell types during embryonic stem cell differentiation.

Transcriptional profiling of the parr–smolt transformation in Atlantic salmon

USGS Publications Warehouse

Robertson, Laura S.; McCormick, Stephen D.

2012-01-01

The parr–smolt transformation in Atlantic salmon (Salmo salar) is a complex developmental process that culminates in the ability to migrate to and live in seawater. We used GRASP 16K cDNA microarrays to identify genes that are differentially expressed in the liver, gill, hypothalamus, pituitary, and olfactory rosettes of smolts compared to parr. Smolts had higher levels of gill Na+/K+-ATPase activity, plasma cortisol and plasma thyroid hormones relative to parr. Across all five tissues, stringent microarray analyses identified 48 features that were differentially expressed in smolts compared to parr. Using a less stringent method we found 477 features that were differentially expressed at least 1.2-fold in smolts, including 172 features in the gill. Smolts had higher mRNA levels of genes involved in transcription, protein biosynthesis and folding, electron transport, oxygen transport, and sensory perception and lower mRNA levels for genes involved in proteolysis. Quantitative RT-PCR was used to confirm differential expression in select genes identified by microarray analyses and to quantify expression of other genes known to be involved in smolting. This study expands our understanding of the molecular processes that underlie smolting in Atlantic salmon and identifies genes for further investigation.

The expression of PTEN in the development of mouse cochlear lateral wall.

PubMed

Dong, Y; Sui, L; Yamaguchi, F; Kamitori, K; Hirata, Y; Hossain, A; Noguchi, C; Katagi, A; Nishio, M; Suzuki, A; Lou, X; Tokuda, M

2014-01-31

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor gene that regulates various cell processes including proliferation, growth, synaptogenesis, neural and glioma stem/progenitor cell renewal. In addition, PTEN can regulate sensory cell proliferation and differentiation of hair bundles in the mammalian cochlea. In this study we use immunofluorescence, Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR) to reveal the expression of PTEN in the developing cochlear lateral wall, which is crucial for regulating K(+) homeostasis. Relatively high levels of PTEN are initially expressed in the marginal cells (MCs) of the lateral wall at embryonic day (E) 17.5 when they start to differentiate. Similarly high levels are subsequently expressed in differentiating root cells (RCs) at postnatal day (P) 3 and then in spiral ligament fibrocytes (SLFs) at P 10. In the mature cochlea, PTEN expression is low or undetectable in MCs and SLFs but it remains high in RCs and their processes. The expression pattern for PTEN in the developing lateral wall suggests that it plays a critical role in the differentiation of the cellular pathways that regulate K(+) homeostasis in the cochlea. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Cell migration under ultrasound irradiations in micrometer scale

NASA Astrophysics Data System (ADS)

Murakami, Shinya; Otsuka, Yo; Oshima, Yusuke; Hikita, Atsuhiko; Mitsui, Toshiyuki

2013-03-01

Cell movements, migration play an important role in many physiological processes including cell proliferation and differentiation. C2C12, a line of mouse myoblasts is known to differentiate into osteoblast under appropriate conditions. Therefore, C2C12 cells can be chosen for the differentiation studies. However, the movement of the C2C12's has not been fully investigated although the movements may provide a better understanding of the healing processes of bone repair, regeneration and differentiation. In addition, low intensity ultrasound has been thought and used to promote bone fracture healing although the microscopic mechanism of this healing is not well understood. As a first step, we have investigated single cell migration of C2C12 under optical microscopy with and without ultrasound irradiations. The ultrasound is irradiated from an apex of a sharp needle. The frequency is 1.5 MHz and the power intensity is near 24 mW/cm2. These values were similar to the ultrasound treatment values. In this conference, we will show the influence of the ultrasound irradiation on the cell movement by plotting the mean squared displacement and the velocity autocorrelation function as a function of time.

Mechanism-based testing strategy using in vitro approaches for identification of thyroid hormone disrupting chemicals

EPA Science Inventory

The thyroid hormone (TH) system is involved in several important physiological processes, including regulation of energy metabolism, growth and differentiation, development and maintenance of brain function, thermo-regulation, osmo-regulation, and axis of regulation of other endo...

Nonlinear GARCH model and 1 / f noise

NASA Astrophysics Data System (ADS)

Kononovicius, A.; Ruseckas, J.

2015-06-01

Auto-regressive conditionally heteroskedastic (ARCH) family models are still used, by practitioners in business and economic policy making, as a conditional volatility forecasting models. Furthermore ARCH models still are attracting an interest of the researchers. In this contribution we consider the well known GARCH(1,1) process and its nonlinear modifications, reminiscent of NGARCH model. We investigate the possibility to reproduce power law statistics, probability density function and power spectral density, using ARCH family models. For this purpose we derive stochastic differential equations from the GARCH processes in consideration. We find the obtained equations to be similar to a general class of stochastic differential equations known to reproduce power law statistics. We show that linear GARCH(1,1) process has power law distribution, but its power spectral density is Brownian noise-like. However, the nonlinear modifications exhibit both power law distribution and power spectral density of the 1 /fβ form, including 1 / f noise.

Large-scale production of human pluripotent stem cell derived cardiomyocytes.

PubMed

Kempf, Henning; Andree, Birgit; Zweigerdt, Robert

2016-01-15

Regenerative medicine, including preclinical studies in large animal models and tissue engineering approaches as well as innovative assays for drug discovery, will require the constant supply of hPSC-derived cardiomyocytes and other functional progenies. Respective cell production processes must be robust, economically viable and ultimately GMP-compliant. Recent research has enabled transition of lab scale protocols for hPSC expansion and cardiomyogenic differentiation towards more controlled processing in industry-compatible culture platforms. Here, advanced strategies for the cultivation and differentiation of hPSCs will be reviewed by focusing on stirred bioreactor-based techniques for process upscaling. We will discuss how cardiomyocyte mass production might benefit from recent findings such as cell expansion at the cardiovascular progenitor state. Finally, remaining challenges will be highlighted, specifically regarding three dimensional (3D) hPSC suspension culture and critical safety issues ahead of clinical translation. Copyright © 2015 Elsevier B.V. All rights reserved.

Transmission ultrasonography. [time delay spectrometry for soft tissue transmission imaging

NASA Technical Reports Server (NTRS)

Heyser, R. C.; Le Croissette, D. H.

1973-01-01

Review of the results of the application of an advanced signal-processing technique, called time delay spectrometry, in obtaining soft tissue transmission images by transmission ultrasonography, both in vivo and in vitro. The presented results include amplitude ultrasound pictures and phase ultrasound pictures obtained by this technique. While amplitude ultrasonographs of tissue are closely analogous to X-ray pictures in that differential absorption is imaged, phase ultrasonographs represent an entirely new source of information based on differential time of propagation. Thus, a new source of information is made available for detailed analysis.

Trichinella spiralis: nurse cell formation with emphasis on analogy to muscle cell repair

PubMed Central

Wu, Zhiliang; Sofronic-Milosavljevic, Lj; Nagano, Isao; Takahashi, Yuzo

2008-01-01

Trichinella infection results in formation of a capsule in infected muscles. The capsule is a residence of the parasite which is composed of the nurse cell and fibrous wall. The process of nurse cell formation is complex and includes infected muscle cell response (de-differentiation, cell cycle re-entry and arrest) and satellite cell responses (activation, proliferation and differentiation). Some events that occur during the nurse cell formation are analogous to those occurring during muscle cell regeneration/repair. This article reviews capsule formation with emphasis on this analogy. PMID:18710582

Note: Quasi-real-time analysis of dynamic near field scattering data using a graphics processing unit

NASA Astrophysics Data System (ADS)

Cerchiari, G.; Croccolo, F.; Cardinaux, F.; Scheffold, F.

2012-10-01

We present an implementation of the analysis of dynamic near field scattering (NFS) data using a graphics processing unit. We introduce an optimized data management scheme thereby limiting the number of operations required. Overall, we reduce the processing time from hours to minutes, for typical experimental conditions. Previously the limiting step in such experiments, the processing time is now comparable to the data acquisition time. Our approach is applicable to various dynamic NFS methods, including shadowgraph, Schlieren and differential dynamic microscopy.

Quantitative proteomics analysis highlights the role of redox hemostasis and energy metabolism in human embryonic stem cell differentiation to neural cells.

PubMed

Fathi, Ali; Hatami, Maryam; Vakilian, Haghighat; Han, Chia-Li; Chen, Yu-Ju; Baharvand, Hossein; Salekdeh, Ghasem Hosseini

2014-04-14

Neural differentiation of human embryonic stem cells (hESCs) is a unique opportunity for in vitro analyses of neurogenesis in humans. Extrinsic cues through neural plate formation are well described in the hESCs although intracellular mechanisms underlying neural development are largely unknown. Proteome analysis of hESC differentiation to neural cells will help to further define molecular mechanisms involved in neurogenesis in humans. Using a two-dimensional differential gel electrophoresis (2D-DIGE) system, we analyzed the proteome of hESC differentiation to neurons at three stages, early neural differentiation, neural ectoderm and mature neurons. Out of 137 differentially accumulated protein spots, 118 spots were identified using MALDI-TOF/TOF and LC MS/MS. We observed that proteins involved in redox hemostasis, vitamin and energy metabolism and ubiquitin dependent proteolysis were more abundant in differentiated cells, whereas the abundance of proteins associated with RNA processing and protein folding was higher in hESCs. Higher abundance of proteins involved in maintaining cellular redox state suggests the importance of redox hemostasis in neural differentiation. Furthermore, our results support the concept of a coupling mechanism between neuronal activity and glucose utilization. The protein network analysis showed that the majority of the interacting proteins were associated with the cell cycle and cellular proliferation. These results enhanced our understanding of the molecular dynamics that underlie neural commitment and differentiation. In highlighting the role of redox and unique metabolic properties of neuronal cells, the present findings add insight to our understanding of hESC differentiation to neurons. The abundance of fourteen proteins involved in maintaining cellular redox state, including 10 members of peroxiredoxin (Prdx) family, mainly increased during differentiation, thus highlighting a link of neural differentiation to redox. Our results revealed markedly higher expression of genes encoding enzymes involved in the glycolysis and amino acid synthesis during differentiation. Protein network analysis predicted a number of critical mediators in hESC differentiation. These proteins included TP53, CTNNB1, SMARCA4, TNF, TERT, E2F1, MYC, RB1, and AR. Copyright © 2014 Elsevier B.V. All rights reserved.

Auxins and tropisms

NASA Technical Reports Server (NTRS)

Muday, G. K.; Brown, C. S. (Principal Investigator)

2001-01-01

Differential growth of plants in response to the changes in the light and gravity vectors requires a complex signal transduction cascade. Although many of the details of the mechanisms by which these differential growth responses are induced are as yet unknown, auxin has been implicated in both gravitropism and phototropism. Specifically, the redistribution of auxin across gravity or light-stimulated tissues has been detected and shown to be required for this process. The approaches by which auxin has been implicated in tropisms include isolation of mutants altered in auxin transport or response with altered gravitropic or phototropic response, identification of auxin gradients with radiolabeled auxin and auxin-inducible gene reporter systems, and by use of inhibitors of auxin transport that block gravitropism and phototropism. Proteins that transport auxin have been identified and the mechanisms which determine auxin transport polarity have been explored. In addition, recent evidence that reversible protein phosphorylation controls this process is summarized. Finally, the data in support of several hypotheses for mechanisms by which auxin transport could be differentially regulated during gravitropism are examined. Although many details of the mechanisms by which plants respond to gravity and light are not yet clear, numerous recent studies demonstrate the role of auxin in these processes.

Estimating Total Electron Content Using 1,000+ GPS Receivers

NASA Technical Reports Server (NTRS)

Komjathy, Attila; Mannucci, Anthony

2006-01-01

A computer program uses data from more than 1,000 Global Positioning System (GPS) receivers in an Internet-accessible global network to generate daily estimates of the global distribution of vertical total electron content (VTEC) of the ionosphere. This program supersedes an older program capable of processing readings from only about 200 GPS receivers. This program downloads the data via the Internet, then processes the data in three stages. In the first stage, raw data from a global subnetwork of about 200 receivers are preprocessed, station by station, in a Kalman-filter-based least-squares estimation scheme that estimates satellite and receiver differential biases for these receivers and for satellites. In the second stage, an observation equation that incorporates the results from the first stage and the raw data from the remaining 800 receivers is solved to obtain the differential biases for these receivers. The only remaining error sources for which an account cannot be given are multipath and receiver noise contributions. The third stage is a postprocessing stage in which all the processed data are combined and used to generate new data products, including receiver differential biases and global and regional VTEC maps and animations.

Sordaria macrospora, a model organism to study fungal cellular development.

PubMed

Engh, Ines; Nowrousian, Minou; Kück, Ulrich

2010-12-01

During the development of multicellular eukaryotes, the processes of cellular growth and organogenesis are tightly coordinated. Since the 1940s, filamentous fungi have served as genetic model organisms to decipher basic mechanisms underlying eukaryotic cell differentiation. Here, we focus on Sordaria macrospora, a homothallic ascomycete and important model organism for developmental biology. During its sexual life cycle, S. macrospora forms three-dimensional fruiting bodies, a complex process involving the formation of different cell types. S. macrospora can be used for genetic, biochemical and cellular experimental approaches since diverse tools, including fluorescence microscopy, a marker recycling system and gene libraries, are available. Moreover, the genome of S. macrospora has been sequenced and allows functional genomics analyses. Over the past years, our group has generated and analysed a number of developmental mutants which has greatly enhanced our fundamental understanding about fungal morphogenesis. In addition, our recent research activities have established a link between developmental proteins and conserved signalling cascades, ultimately leading to a regulatory network controlling differentiation processes in a eukaryotic model organism. This review summarizes the results of our recent findings, thus advancing current knowledge of the general principles and paradigms underpinning eukaryotic cell differentiation and development. Copyright © 2010 Elsevier GmbH. All rights reserved.

Transcriptional regulation of podocyte specification and differentiation.

PubMed

Quaggin, Susan E

2002-05-15

Glomerular visceral epithelial cells (podocytes) are highly specialized cells found in the vertebrate and invertebrate kidney and make up a major portion of the filtration barrier between blood and urinary spaces. During development, specification and differentiation of the podocyte lineage must be tightly orchestrated to produce highly specialized characteristics such as foot processes and slit diaphragms. Furthermore, podocytes are poised to direct incoming endothelial and mesangial cells during glomerular development. They express a number of growth factors that likely play a major role in these processes. Recent findings from transgenic and knockout mouse models and the identification of genes responsible for human podocyte disease have provided insight into transcriptional regulation of some of these processes. These transcription factors include Pax2, WT1 (the Wilms tumor suppressor gene), Pod1 (capsulin, epicardin), Kreisler (maf-1), lmx1b, and mf2. Furthermore, regulatory regions from a podocyte-restricted gene, NPHS1 (nephrin) that are required to direct podocyte-specific expression have been identified from both human and murine genes and provide a tool to further dissect the transcriptional regulation of podocyte-specific gene expression. This article reviews the present state of knowledge regarding transcriptional regulation of podocyte specification and differentiation. Copyright 2002 Wiley-Liss, Inc.

Efficient stage-specific differentiation of human pluripotent stem cells toward retinal photoreceptor cells.

PubMed

Mellough, Carla B; Sernagor, Evelyne; Moreno-Gimeno, Inmaculada; Steel, David H W; Lako, Majlinda

2012-04-01

Recent successes in the stem cell field have identified some of the key chemical and biological cues which drive photoreceptor derivation from human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC); however, the efficiency of this process is variable. We have designed a three-step photoreceptor differentiation protocol combining previously published methods that direct the differentiation of hESC and hiPSC toward a retinal lineage, which we further modified with additional supplements selected on the basis of reports from the eye field and retinal development. We report that hESC and hiPSC differentiating under our regimen over a 60 day period sequentially acquire markers associated with neural, retinal field, retinal pigmented epithelium and photoreceptor cells, including mature photoreceptor markers OPN1SW and RHODOPSIN with a higher efficiency than previously reported. In addition, we report the ability of hESC and hiPSC cultures to generate neural and retinal phenotypes under minimal culture conditions, which may be linked to their ability to endogenously upregulate the expression of a range of factors important for retinal cell type specification. However, cultures that were differentiated with full supplementation under our photoreceptor-induction regimen achieve this within a significantly shorter time frame and show a substantial increase in the expression of photoreceptor-specific markers in comparison to cultures differentiated under minimal conditions. Interestingly, cultures supplemented only with B27 and/or N2 displayed comparable differentiation efficiency to those under full supplementation, indicating a key role for B27 and N2 during the differentiation process. Furthermore, our data highlight an important role for Dkk1 and Noggin in enhancing the differentiation of hESC and hiPSC toward retinal progenitor cells and photoreceptor precursors during the early stages of differentiation, while suggesting that further maturation of these cells into photoreceptors may not require additional factors and can ensue under minimal culture conditions. Copyright © 2012 AlphaMed Press.

Constraints on crystallization of basaltic magma: observations from Kilauea Iki lava lake, Hawaii

NASA Astrophysics Data System (ADS)

Helz, Rosalind

2013-04-01

Kilauea Iki lava lake is a picritic (average MgO = 15.5%) magma body, approximately 135 m thick, which underwent extensive internal differentiation as it cooled and crystallized from its formation during the eruption of 1959 until final solidification in the mid-nineties. Observations of its initial state include data on the stages of filling of the lava lake, plus the sequence and temperature of lava compositions erupted. Drilling and core recovery (from 1960 to 1988) have documented the state of the lake at specific times, showing that the rate of growth of the upper crust was nearly linear (~2.5 m per year between 1962 and 1979), and that the overall pattern of cooling of the lava lake is consistent with conductive heat loss. Recovery and analysis of partially molten drill core has provided a detailed view of the cooling and differentiation history of the melts and minerals within the lake. Observations that may be relevant to older systems include: (1) documentation of when and to what extent olivine settling occurred in the lake; (2) the observation that the most differentiated part of the lake, which lies within the upper crust at a depth of 20-40 m, had completely crystallized by 1975, and (3) the observation that the position of the last interstitial melt was at 80-85 m down, or 62% of the way down in the lake, as would be predicted from conductive cooling. The lava lake lost heat through its roof faster than through the floor, with the result that the position of most-differentiated horizon is grossly offset from the position of the final melt. Circulation patterns in Kilauea Iki were initially driven by lava input during the eruption plus extensive loss of volatiles. These processes significantly affected the location of foundered crust within the lake, as well as the accumulation of coarse, pre-existing olivine phenocrysts between 50 and 95 m. Subsequently, two other major differentiation processes within the lake were driven by upward movement of low-density melts (compositional convection) or of vesicle plumes + melts. These two processes operated vertically, with large-scale motion perpendicular to the (sub-horizontal) isothermal surfaces in the crystallizing mush zones. They have also influenced the grainsize of groundmass minerals throughout the lake. These processes, together with limited olivine settling, have created the existing chemically zoned body. Because of the real-time constraints on when and by what processes the differentiated body that now exists at Kilauea Iki was produced, we can begin to better understand other, older lava lakes and sills, where only the final state is available to us.

Activins and inhibins: Novel regulators of thymocyte development

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

Licona-Limon, Paula; Aleman-Muench, German; Chimal-Monroy, Jesus

2009-04-03

Activins and inhibins are members of the transforming growth factor-{beta} superfamily that act on different cell types and regulate a broad range of cellular processes including proliferation, differentiation, and apoptosis. Here, we provide the first evidence that activins and inhibins regulate specific checkpoints during thymocyte development. We demonstrate that both activin A and inhibin A promote the DN3-DN4 transition in vitro, although they differentially control the transition to the DP stage. Whereas activin A induces the accumulation of a CD8{sup +}CD24{sup hi}TCR{beta}{sup lo} intermediate subpopulation, inhibin A promotes the differentiation of DN4 to DP. In addition, both activin A andmore » inhibin A appear to promote CD8{sup +}SP differentiation. Moreover, inhibin {alpha} null mice have delayed in vitro T cell development, showing both a decrease in the DN-DP transition and reduced thymocyte numbers, further supporting a role for inhibins in the control of developmental signals taking place during T cell differentiation in vivo.« less

Negative emotion differentiation: its personality and well-being correlates and a comparison of different assessment methods.

PubMed

Erbas, Yasemin; Ceulemans, Eva; Lee Pe, Madeline; Koval, Peter; Kuppens, Peter

2014-01-01

Previous research has shown that individual differences in negative emotion differentiation may play a prominent role in well-being. Yet, many basic questions about negative emotion differentiation remain unanswered, including how it relates and overlaps with related and known dimensions of individual differences and what its possible underlying processes are. To answer these questions, in the current article we present three correlational studies that chart the nomological network of individual differences in negative emotion differentiation in terms of personality, difficulties in identifying and describing feelings, and several indicators of well-being, propose a novel paradigm to assess it in the lab, and explore relationships with a possible underlying mechanism in terms of the motivation to approach or avoid emotions. The results affirm consistent relations between negative emotion differentiation and indicators of adjustment like negative affect, self-esteem, neuroticism, depression and meta-knowledge about one's emotions, and show how it is related to the motivation to experience affective states.

Cancer stem cells and differentiation therapy.

PubMed

Jin, Xiong; Jin, Xun; Kim, Hyunggee

2017-10-01

Cancer stem cells can generate tumors from only a small number of cells, whereas differentiated cancer cells cannot. The prominent feature of cancer stem cells is its ability to self-renew and differentiate into multiple types of cancer cells. Cancer stem cells have several distinct tumorigenic abilities, including stem cell signal transduction, tumorigenicity, metastasis, and resistance to anticancer drugs, which are regulated by genetic or epigenetic changes. Like normal adult stem cells involved in various developmental processes and tissue homeostasis, cancer stem cells maintain their self-renewal capacity by activating multiple stem cell signaling pathways and inhibiting differentiation signaling pathways during cancer initiation and progression. Recently, many studies have focused on targeting cancer stem cells to eradicate malignancies by regulating stem cell signaling pathways, and products of some of these strategies are in preclinical and clinical trials. In this review, we describe the crucial features of cancer stem cells related to tumor relapse and drug resistance, as well as the new therapeutic strategy to target cancer stem cells named "differentiation therapy."

Transcriptional, translational, and physiological signatures of undernourished honey bees (Apis mellifera) suggest a role for hormonal factors in hypopharyngeal gland degradation.

PubMed

Corby-Harris, Vanessa; Meador, Charlotte A D; Snyder, Lucy A; Schwan, Melissa R; Maes, Patrick; Jones, Beryl M; Walton, Alexander; Anderson, Kirk E

2016-02-01

Honey bee colonies function as a superorganism, where facultatively sterile female workers perform various tasks that support the hive. Nurse workers undergo numerous anatomical and physiological changes in preparation for brood rearing, including the growth of hypopharyngeal glands (HGs). These glands produce the major protein fraction of a protein- and lipid-rich jelly used to sustain developing larvae. Pollen intake is positively correlated with HG growth, but growth in the first three days is similar regardless of diet, suggesting that initial growth is a pre-determined process while later HG development depends on nutrient availability during a critical window in early adulthood (>3 d). It is unclear whether the resultant size differences in nurse HG are simply due to growth arrest or active degradation of the tissue. To determine what processes cause such differences in HG size, we catalogued the differential expression of both gene transcripts and proteins in the HGs of 8 d old bees that were fed diets containing pollen or no pollen. 3438 genes and 367 proteins were differentially regulated due to nutrition. Of the genes and proteins differentially expressed, undernourished bees exhibited more gene and protein up-regulation compared to well-nourished bees, with the affected processes including salivary gland apoptosis, oogenesis, and hormone signaling. Protein secretion was virtually the only process up-regulated in well-nourished bees. Further assays demonstrated that inhibition of ultraspiracle, one component of the ecdysteroid receptor, in the fat body caused larger HGs. Undernourished bees also had higher acid phosphatase activity, a physiological marker of cell death, compared to well-nourished bees. These results support a connection between poor nutrition, hormonal signaling, and HG degradation. Published by Elsevier Ltd.

Comparative microRNA-seq Analysis Depicts Candidate miRNAs Involved in Skin Color Differentiation in Red Tilapia.

PubMed

Wang, Lanmei; Zhu, Wenbin; Dong, Zaijie; Song, Feibiao; Dong, Juanjuan; Fu, Jianjun

2018-04-16

Differentiation and variation in body color has been a growing limitation to the commercial value of red tilapia. Limited microRNA (miRNA) information is available on skin color differentiation and variation in fish so far. In this study, a high-throughput Illumina sequencing of sRNAs was conducted on three color varieties of red tilapia and 81,394,491 raw reads were generated. A total of 158 differentially expressed miRNAs (|log₂(fold change)| ≥ 1 and q -value ≤ 0.001) were identified. Target prediction and functional analysis of color-related miRNAs showed that a variety of putative target genes—including slc7a11 , mc1r and asip —played potential roles in pigmentation. Moreover; the miRNA-mRNA regulatory network was illustrated to elucidate the pigmentation differentiation, in which miR-138-5p and miR-722 were predicted to play important roles in regulating the pigmentation process. These results advance our understanding of the molecular mechanisms of skin pigmentation differentiation in red tilapia.

Troglitazone induces differentiation in Trypanosoma brucei

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

Denninger, Viola; Figarella, Katherine; Schoenfeld, Caroline

2007-05-15

Trypanosoma brucei, a protozoan parasite causing sleeping sickness, is transmitted by the tsetse fly and undergoes a complex lifecycle including several defined stages within the insect vector and its mammalian host. In the latter, differentiation from the long slender to the short stumpy form is induced by a yet unknown factor of trypanosomal origin. Here we describe that some thiazolidinediones are also able to induce differentiation. In higher eukaryotes, thiazolidinediones are involved in metabolism and differentiation processes mainly by binding to the intracellular receptor peroxisome proliferator activated receptor {gamma}. Our studies focus on the effects of troglitazone on bloodstream formmore » trypanosomes. Differentiation was monitored using mitochondrial markers (membrane potential, succinate dehydrogenase activity, inhibition of oxygen uptake by KCN, amount of cytochrome transcripts), morphological changes (Transmission EM and light microscopy), and transformation experiments (loss of the Variant Surface Glycoprotein coat and increase of dihydroliponamide dehydrogenase activity). To further investigate the mechanisms responsible for these changes, microarray analyses were performed, showing an upregulation of expression site associated gene 8 (ESAG8), a potential differentiation regulator.« less

GCKP84-general chemical kinetics code for gas-phase flow and batch processes including heat transfer effects

NASA Technical Reports Server (NTRS)

Bittker, D. A.; Scullin, V. J.

1984-01-01

A general chemical kinetics code is described for complex, homogeneous ideal gas reactions in any chemical system. The main features of the GCKP84 code are flexibility, convenience, and speed of computation for many different reaction conditions. The code, which replaces the GCKP code published previously, solves numerically the differential equations for complex reaction in a batch system or one dimensional inviscid flow. It also solves numerically the nonlinear algebraic equations describing the well stirred reactor. A new state of the art numerical integration method is used for greatly increased speed in handling systems of stiff differential equations. The theory and the computer program, including details of input preparation and a guide to using the code are given.

Th9 cells: differentiation and disease

PubMed Central

Kaplan, Mark H.

2014-01-01

Summary CD4+ T-helper cells regulate immunity and inflammation through the acquisition of potential to secrete specific cytokines. The acquisition of cytokine-secreting potential, in a process termed T-helper cell differentiation, is a response to multiple environmental signals including the cytokine milieu. The most recently defined subset of T-helper cells are termed Th9 and are identified by the potent production of interleukin-9 (IL-9). Given the pleiotropic functions of IL-9, Th9 cells might be involved in pathogen immunity and immune-mediated disease. In this review, I focus on recent developments in understanding the signals that promote Th9 differentiation, the transcription factors that regulate IL-9 expression, and finally the potential roles for Th9 cells in immunity in vivo. PMID:23405898

Emotion-Related Self-Regulation in Children

ERIC Educational Resources Information Center

Eisenberg, Nancy; Sulik, Michael J.

2012-01-01

In this article, the authors review basic conceptual issues in research on children's emotion-related self-regulation, including the differentiation between self-regulation that is effortful and voluntary and control-related processes that are less amenable to effortful control. In addition, the authors summarize what researchers know about…

EVALUATING THE ABILITY OF IN VITRO ASSAYS BASED ON KEY EVENTS IN NEURODEVELOPMENT TO PREDICT DEVELOPMENTAL NEUROTOXICITY (DNT)

EPA Science Inventory

USABecause of the multitude of potential molecular targets for chemical disruption in the developing nervous system, our laboratory has developed in vitro assays that measure chemical disruption of key neurodevelopmental processes. These include proliferation, differentiation, ap...

Lesson Plans in Urban Economics.

ERIC Educational Resources Information Center

Alexander, Albert

1990-01-01

Traces history of urbanization and problems created by growth of cities. Describes process of homogenization achieved by land-use regulations, income and education differentiation, and racial/ethnic characteristics. Focuses on the sociopolitical-economic challenges of the 1990s. Includes format for three lessons with a case study project and…

Nutritional Factors Affecting Adult Neurogenesis and Cognitive Function

USDA-ARS?s Scientific Manuscript database

Adult neurogenesis, a complex process by which stem cells in the hippocampal brain region differentiate and proliferate into new neurons and other resident brain cells, is known to be affected by many intrinsic and extrinsic factors, including diet. Neurogenesis plays a critical role in neural plas...

THE NEUROTOXICANT TRIMETHYLTIN INDUCES APOPTOSIS VIA CASPASE ACTIVATION, P38 PROTEIN KINASE, AND OXIDATIVE STRESS IN PC12 CELLS.

EPA Science Inventory

This manuscript describes in vitro cell signaling mechanisms involved in trimethyltin-induced neurotoxicity. The signaling pathways and effects presage effects on developmental process including neural differentiation and apoptosis. These mechanisms may be pertinent to other orga...

Secretome analysis to elucidate metalloprotease-dependent ectodomain shedding of glycoproteins during neuronal differentiation.

PubMed

Tsumagari, Kazuya; Shirakabe, Kyoko; Ogura, Mayu; Sato, Fuminori; Ishihama, Yasushi; Sehara-Fujisawa, Atsuko

2017-02-01

Many membrane proteins are subjected to limited proteolyses at their juxtamembrane regions, processes referred to as ectodomain shedding. Shedding ectodomains of membrane-bound ligands results in activation of downstream signaling pathways, whereas shedding those of cell adhesion molecules causes loss of cell-cell contacts. Secreted proteomics (secretomics) using high-resolution mass spectrometry would be strong tools for both comprehensive identification and quantitative measurement of membrane proteins that undergo ectodomain shedding. In this study, to elucidate the ectodomain shedding events that occur during neuronal differentiation, we establish a strategy for quantitative secretomics of glycoproteins released from differentiating neuroblastoma cells into culture medium with or without GM6001, a broad-spectrum metalloprotease inhibitor. Considering that most of transmembrane and secreted proteins are N-glycosylated, we include a process of N-glycosylated peptides enrichment as well as isotope tagging in our secretomics workflow. Our results show that differentiating N1E-115 neurons secrete numerous glycosylated polypeptides in metalloprotease-dependent manners. They are derived from cell adhesion molecules such as NCAM1, CADM1, L1CAM, various transporters and receptor proteins. These results show the landscape of ectodomain shedding and other secretory events in differentiating neurons and/or during axon elongation, which should help elucidate the mechanism of neurogenesis and the pathogenesis of neurological disorders. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

Liver-enriched transcription factors are critical for the expression of hepatocyte marker genes in mES-derived hepatocyte-lineage cells.

PubMed

Kheolamai, Pakpoom; Dickson, Alan J

2009-04-23

Induction of stem cell differentiation toward functional hepatocytes is hampered by lack of knowledge of the hepatocyte differentiation processes. The overall objective of this project is to characterize key stages in the hepatocyte differentiation process. We established a mouse embryonic stem (mES) cell culture system which exhibited changes in gene expression profiles similar to those observed in the development of endodermal and hepatocyte-lineage cells previously described in the normal mouse embryo. Transgenic mES cells were established that permitted isolation of enriched hepatocyte-lineage populations. This approach has isolated mES-derived hepatocyte-lineage cells that express several markers of mature hepatocytes including albumin, glucose-6-phosphatase, tyrosine aminotransferase, cytochrome P450-3a, phosphoenolpyruvate carboxykinase and tryptophan 2,3-dioxygenase. In addition, our results show that the up-regulation of the expression levels of hepatocyte nuclear factor-3alpha, -4alpha, -6, and CCAAT-enhancer binding protein-beta might be critical for passage into late-stage differentiation towards functional hepatocytes. These data present important steps for definition of regulatory phenomena that direct specific cell fate determination. The mES cell culture system generated in this study provides a model for studying transition between stages of the hepatocyte development and has significant potential value for studying the molecular basis of hepatocyte differentiation in vitro.

The C. elegans SoxC protein SEM-2 opposes differentiation factors to promote a proliferative blast cell fate in the postembryonic mesoderm

PubMed Central

Tian, Chenxi; Shi, Herong; Colledge, Clark; Stern, Michael; Waterston, Robert; Liu, Jun

2011-01-01

The proper development of multicellular organisms requires precise regulation and coordination of cell fate specification, cell proliferation and differentiation. Abnormal regulation and coordination of these processes could lead to disease, including cancer. We have examined the function of the sole C. elegans SoxC protein, SEM-2, in the M lineage, which produces the postembryonic mesoderm. We found that SEM-2/SoxC is both necessary and sufficient to promote a proliferating blast cell fate, the sex myoblast fate, over a differentiated striated bodywall muscle fate. A number of factors control the specific expression of sem-2 in the sex myoblast precursors and their descendants. This includes direct control of sem-2 expression by a Hox-PBC complex. The crucial nature of the HOX/PBC factors in directly enhancing expression of this proliferative factor in the C. elegans M lineage suggests a possible more general link between Hox-PBC factors and SoxC proteins in regulating cell proliferation. PMID:21307099

Auto-Bäcklund transformations for a matrix partial differential equation

NASA Astrophysics Data System (ADS)

Gordoa, P. R.; Pickering, A.

2018-07-01

We derive auto-Bäcklund transformations, analogous to those of the matrix second Painlevé equation, for a matrix partial differential equation. We also then use these auto-Bäcklund transformations to derive matrix equations involving shifts in a discrete variable, a process analogous to the use of the auto-Bäcklund transformations of the matrix second Painlevé equation to derive a discrete matrix first Painlevé equation. The equations thus derived then include amongst other examples a semidiscrete matrix equation which can be considered to be an extension of this discrete matrix first Painlevé equation. The application of this technique to the auto-Bäcklund transformations of the scalar case of our partial differential equation has not been considered before, and so the results obtained here in this scalar case are also new. Other equations obtained here using this technique include a scalar semidiscrete equation which arises in the case of the second Painlevé equation, and which does not seem to have been thus derived previously.

PLA-poloxamer/poloxamine copolymers for ligament tissue engineering: sound macromolecular design for degradable scaffolds and MSC differentiation.

PubMed

Leroy, Adrien; Nottelet, Benjamin; Bony, Claire; Pinese, Coline; Charlot, Benoît; Garric, Xavier; Noël, Danièle; Coudane, Jean

2015-04-01

The treatment of anterior cruciate ligament (ACL) failures remains a current clinical challenge. The present study aims at providing suitable degradable scaffolds for ligament tissue engineering. First, we focus on the design and the evaluation of poly(lactide)/poloxamer or poly(lactide)/poloxamine multiblock copolymers selected and developed to have suitable degradation and mechanical properties to match ACL repair. In the second part, it is shown that the copolymers can be processed in the form of microfibers and scaffolds consisting of a combination of twisted/braided fibers to further modulate the mechanical properties and prepare scaffold prototypes suitable for ligament application. Finally, after assessment of their cytocompatibility, the polymer scaffolds are associated with mesenchymal stem cells (MSCs). MSC differentiation toward a ligament fibroblast phenotype is promoted by a dual stimulation including an inductive culture medium and cyclic mechanical loads. RT-qPCR analyses confirm the potential of our scaffolds and MSCs for ACL regeneration with upregulation of some differentiation markers including Scleraxis, Tenascin-C and Tenomodulin.

Transcriptome analysis of symptomatic and recovered leaves of geminivirus-infected pepper (Capsicum annuum)

PubMed Central

2012-01-01

Background Geminiviruses are a large and important family of plant viruses that infect a wide range of crops throughout the world. The Begomovirus genus contains species that are transmitted by whiteflies and are distributed worldwide causing disease on an array of horticultural crops. Symptom remission, in which newly developed leaves of systemically infected plants exhibit a reduction in symptom severity (recovery), has been observed on pepper (Capsicum annuum) plants infected with Pepper golden mosaic virus (PepGMV). Previous studies have shown that transcriptional and post-transcriptional gene silencing mechanisms are involved in the reduction of viral nucleic acid concentration in recovered tissue. In this study, we employed deep transcriptome sequencing methods to assess transcriptional variation in healthy (mock), symptomatic, and recovered pepper leaves following PepGMV infection. Results Differential expression analyses of the pepper leaf transcriptome from symptomatic and recovered stages revealed a total of 309 differentially expressed genes between healthy (mock) and symptomatic or recovered tissues. Computational prediction of differential expression was validated using quantitative reverse-transcription PCR confirming the robustness of our bioinformatic methods. Within the set of differentially expressed genes associated with the recovery process were genes involved in defense responses including pathogenesis-related proteins, reactive oxygen species, systemic acquired resistance, jasmonic acid biosynthesis, and ethylene signaling. No major differences were found when compared the differentially expressed genes in symptomatic and recovered tissues. On the other hand, a set of genes with novel roles in defense responses was identified including genes involved in histone modification. This latter result suggested that post-transcriptional and transcriptional gene silencing may be one of the major mechanisms involved in the recovery process. Genes orthologous to the C. annuum proteins involved in the pepper-PepGMV recovery response were identified in both Solanum lycopersicum and Solanum tuberosum suggesting conservation of components of the viral recovery response in the Solanaceae. Conclusion These data provide a valuable source of information for improving our understanding of the underlying molecular mechanisms by which pepper leaves become symptomless following infection with geminiviruses. The identification of orthologs for the majority of genes differentially expressed in recovered tissues in two major solanaceous crop species provides the basis for future comparative analyses of the viral recovery process across related taxa. PMID:23185982

Transcriptome analysis of symptomatic and recovered leaves of geminivirus-infected pepper (Capsicum annuum).

PubMed

Góngora-Castillo, Elsa; Ibarra-Laclette, Enrique; Trejo-Saavedra, Diana L; Rivera-Bustamante, Rafael F

2012-11-27

Geminiviruses are a large and important family of plant viruses that infect a wide range of crops throughout the world. The Begomovirus genus contains species that are transmitted by whiteflies and are distributed worldwide causing disease on an array of horticultural crops. Symptom remission, in which newly developed leaves of systemically infected plants exhibit a reduction in symptom severity (recovery), has been observed on pepper (Capsicum annuum) plants infected with Pepper golden mosaic virus (PepGMV). Previous studies have shown that transcriptional and post-transcriptional gene silencing mechanisms are involved in the reduction of viral nucleic acid concentration in recovered tissue. In this study, we employed deep transcriptome sequencing methods to assess transcriptional variation in healthy (mock), symptomatic, and recovered pepper leaves following PepGMV infection. Differential expression analyses of the pepper leaf transcriptome from symptomatic and recovered stages revealed a total of 309 differentially expressed genes between healthy (mock) and symptomatic or recovered tissues. Computational prediction of differential expression was validated using quantitative reverse-transcription PCR confirming the robustness of our bioinformatic methods. Within the set of differentially expressed genes associated with the recovery process were genes involved in defense responses including pathogenesis-related proteins, reactive oxygen species, systemic acquired resistance, jasmonic acid biosynthesis, and ethylene signaling. No major differences were found when compared the differentially expressed genes in symptomatic and recovered tissues. On the other hand, a set of genes with novel roles in defense responses was identified including genes involved in histone modification. This latter result suggested that post-transcriptional and transcriptional gene silencing may be one of the major mechanisms involved in the recovery process. Genes orthologous to the C. annuum proteins involved in the pepper-PepGMV recovery response were identified in both Solanum lycopersicum and Solanum tuberosum suggesting conservation of components of the viral recovery response in the Solanaceae. These data provide a valuable source of information for improving our understanding of the underlying molecular mechanisms by which pepper leaves become symptomless following infection with geminiviruses. The identification of orthologs for the majority of genes differentially expressed in recovered tissues in two major solanaceous crop species provides the basis for future comparative analyses of the viral recovery process across related taxa.

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.

The Screening of Genes Sensitive to Long-Term, Low-Level Microwave Exposure and Bioinformatic Analysis of Potential Correlations to Learning and Memory.

PubMed

Zhao, Ya Li; Li, Ying Xian; Ma, Hong Bo; Li, Dong; Li, Hai Liang; Jiang, Rui; Kan, Guang Han; Yang, Zhen Zhong; Huang, Zeng Xin

2015-08-01

To gain a better understanding of gene expression changes in the brain following microwave exposure in mice. This study hopes to reveal mechanisms contributing to microwave-induced learning and memory dysfunction. Mice were exposed to whole body 2100 MHz microwaves with specific absorption rates (SARs) of 0.45 W/kg, 1.8 W/kg, and 3.6 W/kg for 1 hour daily for 8 weeks. Differentially expressing genes in the brains were screened using high-density oligonucleotide arrays, with genes showing more significant differences further confirmed by RT-PCR. The gene chip results demonstrated that 41 genes (0.45 W/kg group), 29 genes (1.8 W/kg group), and 219 genes (3.6 W/kg group) were differentially expressed. GO analysis revealed that these differentially expressed genes were primarily involved in metabolic processes, cellular metabolic processes, regulation of biological processes, macromolecular metabolic processes, biosynthetic processes, cellular protein metabolic processes, transport, developmental processes, cellular component organization, etc. KEGG pathway analysis showed that these genes are mainly involved in pathways related to ribosome, Alzheimer's disease, Parkinson's disease, long-term potentiation, Huntington's disease, and Neurotrophin signaling. Construction of a protein interaction network identified several important regulatory genes including synbindin (sbdn), Crystallin (CryaB), PPP1CA, Ywhaq, Psap, Psmb1, Pcbp2, etc., which play important roles in the processes of learning and memorye. Long-term, low-level microwave exposure may inhibit learning and memory by affecting protein and energy metabolic processes and signaling pathways relating to neurological functions or diseases. Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Differential diagnosis of a patient referred to physical therapy with neck pain: a case study of a patient with an atypical presentation of angina.

PubMed

Mathers, Jessie J

2012-11-01

A 64-year-old man with acute onset neck pain was referred to physical therapy by a neurosurgeon. The purpose of this case study is to examine the process of differential diagnosis in a patient with neck pain and to discuss common diagnostic errors that can occur in the outpatient setting. The patient had an 8-week history of neck pain, which was worse when running and lifting objects. He presented with imaging of the cervical spine demonstrating degenerative changes. During the examination, several differential diagnoses were considered. A thorough physical examination of the cervical spine and upper quarter failed to reproduce his symptoms. At that time, the physical therapist was suspicious that the origin of the patient's neck pain was non-mechanical in nature. Additional testing during the examination included having the patient exercise briefly on gym equipment; this reproduced his symptoms. After additional positional and postural changes did not alleviate the symptoms, he stopped exercising, and his pain ceased. The patient was referred back to his primary care physician who ordered cardiovascular testing including an electrocardiogram and echocardiogram. These tests revealed significant cardiac abnormalities including multi-vessel blockage of the coronary arteries and evidence of infarction. He underwent a coronary artery bypass graft 4 days later. To make an appropriate differential diagnosis, physical therapists must use a patient-centered model of clinical reasoning and meta-cognition and have an awareness of diagnostic errors such that they can be avoided. The goal of the physical therapy examination, including differential diagnosis, is to efficiently classify the patient for treatment or to direct patients to the proper healthcare provider, thereby minimizing and preventing mortality and morbidity.

Characterization and differential expression of microRNAs elicited by sulfur deprivation in Chlamydomonas reinhardtii

PubMed Central

2012-01-01

Background microRNAs (miRNAs) have been found to play an essential role in the modulation of numerous biological processes in eukaryotes. Chlamydomonas reinhardtii is an ideal model organism for the study of many metabolic processes including responses to sulfur-deprivation. We used a deep sequencing platform to extensively profile and identify changes in the miRNAs expression that occurred under sulfur-replete and sulfur-deprived conditions. The aim of our research was to characterize the differential expression of Chlamydomonas miRNAs under sulfur-deprived conditions, and subsequently, the target genes of miRNA involved in sulfur-deprivation were further predicted and analyzed. Results By using high-throughput sequencing, we characterized the microRNA transcriptomes under sulphur-replete and sulfur-deprived conditions in Chlamydomonas reinhardtii. We predicted a total of 310 miRNAs which included 85 known miRNAs and 225 novel miRNAs. 13 miRNAs were the specific to the sulfur-deprived conditions. 47 miRNAs showed significantly differential expressions responding to sulfur-deprivation, and most were up-regulated in the small RNA libraries with sulfur-deprivation. Using a web-based integrated system (Web MicroRNAs Designer 3) and combing the former information from a transcriptome of Chlamydomonas reinhardtii, 22 miRNAs and their targets involved in metabolism regulation with sulfur-deprivation were verified. Conclusions Our results indicate that sulfur-deprivation may have a significant influence on small RNA expression patterns, and the differential expressions of miRNAs and interactions between miRNA and its targets might further reveal the molecular mechanism responding to sulfur-deprivation in Chlamydomonas reinhardtii. PMID:22439676

Stochastic differential equation model for linear growth birth and death processes with immigration and emigration

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

Granita, E-mail: granitafc@gmail.com; Bahar, A.

This paper discusses on linear birth and death with immigration and emigration (BIDE) process to stochastic differential equation (SDE) model. Forward Kolmogorov equation in continuous time Markov chain (CTMC) with a central-difference approximation was used to find Fokker-Planckequation corresponding to a diffusion process having the stochastic differential equation of BIDE process. The exact solution, mean and variance function of BIDE process was found.

IBT-based quantitative proteomics identifies potential regulatory proteins involved in pigmentation of purple sea cucumber, Apostichopus japonicus.

PubMed

Xing, Lili; Sun, Lina; Liu, Shilin; Li, Xiaoni; Zhang, Libin; Yang, Hongsheng

2017-09-01

Sea cucumbers are an important economic species and exhibit high yield value among aquaculture animals. Purple sea cucumbers are very rare and beautiful and have stable hereditary patterns. In this study, isobaric tags (IBT) were first used to reveal the molecular mechanism of pigmentation in the body wall of the purple sea cucumber. We analyzed the proteomes of purple sea cucumber in early pigmentation stage (Pa), mid pigmentation stage (Pb) and late pigmentation stage (Pc), resulting in the identification of 5580 proteins, including 1099 differentially expressed proteins in Pb: Pa and 339 differentially expressed proteins in Pc: Pb. GO and KEGG analyses revealed possible differentially expressed proteins, including"melanogenesis", "melanosome", "melanoma", "pigment-biosynthetic process", "Epidermis development", "Ras-signaling pathway", "Wnt-signaling pathway", "response to UV light", and "tyrosine metabolism", involved in pigment synthesis and regulation in purple sea cucumbers. The large number of differentially expressed proteins identified here should be highly useful in further elucidating the mechanisms underlying pigmentation in sea cucumbers. Furthermore, these results may also provide the base for further identification of proteins involved in resistance mechanisms against melanoma, albinism, UV damage, and other diseases in sea cucumbers. Copyright © 2017. Published by Elsevier Inc.

ASSESSMENT OF PC12 CELL DIFFERENTIATION AND NEURITE GROWTH: A COMPARISON OF MORPHOLOGICAL AND NEUROCHEMICAL MEASURES.

EPA Science Inventory

In order to screen large numbers of chemicals for their potential to produce developmental neurotoxicity new, in vitro methods are needed. One approach is to develop methods based on the biologic processes which underlie brain development including the growth and maturation of ce...

The effects of Capn1 gene inactivation on the differential expression of genes in skeletal muscle

USDA-ARS?s Scientific Manuscript database

Protein turnover is required for muscle growth and regeneration and several proteolytic enzymes, including the calpains, degrade myofibrillar proteins during this process. In a previous experiment, phenotypic differences were observed between µ-calpain knockout (KO) and wild type (WT) mice, includin...

A Quantitative Acetylomic Analysis of Early Seed Development in Rice (Oryza sativa L.).

PubMed

Wang, Yifeng; Hou, Yuxuan; Qiu, Jiehua; Li, Zhiyong; Zhao, Juan; Tong, Xiaohong; Zhang, Jian

2017-06-27

PKA (protein lysine acetylation) is a critical post-translational modification that regulates various developmental processes, including seed development. However, the acetylation events and dynamics on a proteomic scale in this process remain largely unknown, especially in rice early seed development. We report the first quantitative acetylproteomic study focused on rice early seed development by employing a mass spectral-based (MS-based), label-free approach. A total of 1817 acetylsites on 1688 acetylpeptides from 972 acetylproteins were identified in pistils and seeds at three and seven days after pollination, including 268 acetyproteins differentially acetylated among the three stages. Motif-X analysis revealed that six significantly enriched motifs, such as (DxkK), (kH) and (kY) around the acetylsites of the identified rice seed acetylproteins. Differentially acetylated proteins among the three stages, including adenosine diphosphate (ADP) -glucose pyrophosphorylases (AGPs), PDIL1-1 (protein disulfide isomerase like 1-1), hexokinases, pyruvate dehydrogenase complex (PDC) and numerous other regulators that are extensively involved in the starch and sucrose metabolism, glycolysis/gluconeogenesis, tricarboxylic acid (TCA) cycle and photosynthesis pathways during early seed development. This study greatly expanded the rice acetylome dataset, and shed novel insight into the regulatory roles of PKA in rice early seed development.

Osteogenic differentiation capacity of human skeletal muscle-derived progenitor cells.

PubMed

Oishi, Teruyo; Uezumi, Akiyoshi; Kanaji, Arihiko; Yamamoto, Naoki; Yamaguchi, Asami; Yamada, Harumoto; Tsuchida, Kunihiro

2013-01-01

Heterotopic ossification (HO) is defined as the formation of ectopic bone in soft tissue outside the skeletal tissue. HO is thought to result from aberrant differentiation of osteogenic progenitors within skeletal muscle. However, the precise origin of HO is still unclear. Skeletal muscle contains two kinds of progenitor cells, myogenic progenitors and mesenchymal progenitors. Myogenic and mesenchymal progenitors in human skeletal muscle can be identified as CD56(+) and PDGFRα(+) cells, respectively. The purpose of this study was to investigate the osteogenic differentiation potential of human skeletal muscle-derived progenitors. Both CD56(+) cells and PDGFRα(+) cells showed comparable osteogenic differentiation potential in vitro. However, in an in vivo ectopic bone formation model, PDGFRα(+) cells formed bone-like tissue and showed successful engraftment, while CD56(+) cells did not form bone-like tissue and did not adapt to an osteogenic environment. Immunohistological analysis of human HO sample revealed that many PDGFRα(+) cells were localized in proximity to ectopic bone formed in skeletal muscle. MicroRNAs (miRNAs) are known to regulate many biological processes including osteogenic differentiation. We investigated the participation of miRNAs in the osteogenic differentiation of PDGFRα(+) cells by using microarray. We identified miRNAs that had not been known to be involved in osteogenesis but showed dramatic changes during osteogenic differentiation of PDGFRα(+) cells. Upregulation of miR-146b-5p and -424 and downregulation of miR-7 during osteogenic differentiation of PDGFRα(+) cells were confirmed by quantitative real-time RT-PCR. Inhibition of upregulated miRNAs, miR-146b-5p and -424, resulted in the suppression of osteocyte maturation, suggesting that these two miRNAs have the positive role in the osteogenesis of PDGFRα(+) cells. Our results suggest that PDGFRα(+) cells may be the major source of HO and that the newly identified miRNAs may regulate osteogenic differentiation process of PDGFRα(+) cells.

MicroRNA-24 promotes 3T3-L1 adipocyte differentiation by directly targeting the MAPK7 signaling

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

Jin, Min, E-mail: min_jin@zju.edu.cn; Wu, Yutao; Wang, Jing

Over the past years, MicroRNAs (miRNAs) act as a vital role in harmony with gene regulation and maintaining cellular homeostasis. It is well testified that miRNAshave been involved in numerous physiological and pathological processes, including embryogenesis, cell fate decision, and cellular differentiation. Adipogenesis is an organized process of cellular differentiation by which pre-adipocytes differentiate towards mature adipocytes, and it is tightly modulated by a series of transcription factors such as peroxisome proliferator-activated receptor γ (PPAR-γ) and sterol regulatory-element binding proteins 1 (SREBP1). However, the molecular mechanisms underlying the connection between miRNAs and adipogenesis-related transcription factors remain obscure. In this study,more » we unveiled that miR- 24 was remarkably upregulated during 3T3-L1 adipogenesis. Overexpression of miR-24 significantly promoted 3T3-L1 adipogenesis, as evidenced by its ability to increase the expression of PPAR-γ and SREBP1, lipid droplet formation and triglyceride (TG) accumulation. Furthermore, we found that neither ectopic expression of miR-24nor miR-24 inhibitor affect cell proliferation and cell cycle progression. Finally, we demonstrated that miR-24 plays the modulational role by directly repressing MAPK7, a key number in the MAPK signaling pathway. These data indicate that miR-24 is a novel positive regulator of adipocyte differentiation by targeting MAPK7, which provides new insights into the molecular mechanism of miRNA-mediated cellular differentiation. -- Highlights: •We firstly found miR-24 was upregulated in 3T3-L1 pre-adipocytes differentiation. •miR-24 promoted 3T3-L1 pre-adipocytes differentiation while silencing the expression of miR-24 had an opposite function. •miR-24 regulated 3T3-L1 differentiation by directly targeting MAPK7 signaling pathway. •miR-24did not affect 3T3-L1 pre-adipocytes cellular proliferation.« less

Resveratrol Ameliorates the Maturation Process of β-Cell-Like Cells Obtained from an Optimized Differentiation Protocol of Human Embryonic Stem Cells

PubMed Central

Pezzolla, Daniela; López-Beas, Javier; Lachaud, Christian C.; Domínguez-Rodríguez, Alejandro; Smani, Tarik; Hmadcha, Abdelkrim; Soria, Bernat

2015-01-01

Human embryonic stem cells (hESCs) retain the extraordinary capacity to differentiate into different cell types of an adult organism, including pancreatic β-cells. For this particular lineage, although a lot of effort has been made in the last ten years to achieve an efficient and reproducible differentiation protocol, it was not until recently that this aim was roughly accomplished. Besides, several studies evidenced the impact of resveratrol (RSV) on insulin secretion, even though the mechanism by which this polyphenol potentiates glucose-stimulated insulin secretion (GSIS) is still not clear. The aim of this study was to optimize an efficient differentiation protocol that mimics in vivo pancreatic organogenesis and to investigate whether RSV may improve the final maturation step to obtain functional insulin-secreting cells. Our results indicate that treatment of hESCs (HS-181) with activin-A induced definitive endoderm differentiation as detected by the expression of SOX17 and FOXA2. Addition of retinoic acid (RA), Noggin and Cyclopamine promoted pancreatic differentiation as indicated by the expression of the early pancreatic progenitor markers ISL1, NGN3 and PDX1. Moreover, during maturation in suspension culture, differentiating cells assembled in islet-like clusters, which expressed specific endocrine markers such as PDX1, SST, GCG and INS. Similar results were confirmed with the human induced Pluripotent Stem Cell (hiPSC) line MSUH-001. Finally, differentiation protocols incorporating RSV treatment yielded numerous insulin-positive cells, induced significantly higher PDX1 expression and were able to transiently normalize glycaemia when transplanted in streptozotocin (STZ) induced diabetic mice thus promoting its survival. In conclusion, our strategy allows the efficient differentiation of hESCs into pancreatic endoderm capable of generating β-cell-like cells and demonstrates that RSV improves the maturation process. PMID:25774684

Three-dimensional neural differentiation of embryonic stem cells with ACM induction in microfibrous matrices in bioreactors.

PubMed

Liu, Ning; Ouyang, Anli; Li, Yan; Yang, Shang-Tian

2013-01-01

The clinical use of pluripotent stem cell (PSC)-derived neural cells requires an efficient differentiation process for mass production in a bioreactor. Toward this goal, neural differentiation of murine embryonic stem cells (ESCs) in three-dimensional (3D) polyethylene terephthalate microfibrous matrices was investigated in this study. To streamline the process and provide a platform for process integration, the neural differentiation of ESCs was induced with astrocyte-conditioned medium without the formation of embryoid bodies, starting from undifferentiated ESC aggregates expanded in a suspension bioreactor. The 3D neural differentiation was able to generate a complex neural network in the matrices. When compared to 2D differentiation, 3D differentiation in microfibrous matrices resulted in a higher percentage of nestin-positive cells (68% vs. 54%) and upregulated gene expressions of nestin, Nurr1, and tyrosine hydroxylase. High purity of neural differentiation in 3D microfibrous matrix was also demonstrated in a spinner bioreactor with 74% nestin + cells. This study demonstrated the feasibility of a scalable process based on 3D differentiation in microfibrous matrices for the production of ESC-derived neural cells. © 2013 American Institute of Chemical Engineers.

Transcriptomic Analysis Reveals Mechanisms of Sterile and Fertile Flower Differentiation and Development in Viburnum macrocephalum f. keteleeri

PubMed Central

Lu, Zhaogeng; Xu, Jing; Li, Weixing; Zhang, Li; Cui, Jiawen; He, Qingsong; Wang, Li; Jin, Biao

2017-01-01

Sterile and fertile flowers are an important evolutionary developmental (evo-devo) phenotype in angiosperm flowers, playing important roles in pollinator attraction and sexual reproductive success. However, the gene regulatory mechanisms underlying fertile and sterile flower differentiation and development remain largely unknown. Viburnum macrocephalum f. keteleeri, which possesses fertile and sterile flowers in a single inflorescence, is a useful candidate species for investigating the regulatory networks in differentiation and development. We developed a de novo-assembled flower reference transcriptome. Using RNA sequencing (RNA-seq), we compared the expression patterns of fertile and sterile flowers isolated from the same inflorescence over its rapid developmental stages. The flower reference transcriptome consisted of 105,683 non-redundant transcripts, of which 5,675 transcripts showed significant differential expression between fertile and sterile flowers. Combined with morphological and cytological changes between fertile and sterile flowers, we identified expression changes of many genes potentially involved in reproductive processes, phytohormone signaling, and cell proliferation and expansion using RNA-seq and qRT-PCR. In particular, many transcription factors (TFs), including MADS-box family members and ABCDE-class genes, were identified, and expression changes in TFs involved in multiple functions were analyzed and highlighted to determine their roles in regulating fertile and sterile flower differentiation and development. Our large-scale transcriptional analysis of fertile and sterile flowers revealed the dynamics of transcriptional networks and potentially key components in regulating differentiation and development of fertile and sterile flowers in Viburnum macrocephalum f. keteleeri. Our data provide a useful resource for Viburnum transcriptional research and offer insights into gene regulation of differentiation of diverse evo-devo processes in flowers. PMID:28298915

MicroRNA, miR-374b, directly targets Myf6 and negatively regulates C2C12 myoblasts differentiation

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

Ma, Zhiyuan; Sun, Xiaorui; Xu, Dequan

Myogenesis is a complex process including myoblast proliferation, differentiation and myotube formation and is controlled by myogenic regulatory factors (MRFs), MyoD, MyoG, Myf5 and Myf6 (also known as MRF4). MicroRNA is a kind of ∼22 nt-long non-coding small RNAs, and act as key transcriptional or post-transcriptional regulators of gene expression. Identification of miRNAs involved in the regulation of muscle genes could improve our understanding of myogenesis process. In this study, we investigated the regulation of Myf6 gene by miRNAs. We showed that miR-374b specifically bound to the 3'untranslated region (UTR) of Myf6 and down-regulated the expression of Myf6 gene at bothmore » mRNA and protein level. Furthermore, miR-374b is ubiquitously expressed in the tissues of adult C57BL6 mouse, and the mRNA abundance increases first and then decreases during C2C12 myoblasts differentiation. Over-expression of miR-374b impaired C2C12 cell differentiation, while inhibiting miR-374b expression by 2′-O-methyl antisense oligonucleotides promoted C2C12 cell differentiation. Taken together, our findings identified miR-374b directly targets Myf6 and negatively regulates myogenesis. - Highlights: • MiR-374b directly targets 3′UTR of Myf6. • MiR-374b negatively regulates Myf6 in C2C12 cells. • MiR-374b abundance significiently changes during C2C12 cells differentiation. • MiR-374b negatively regulates C2C12 cells differentiation.« less

The organic osmolyte betaine induces keratin 2 expression in rat epidermal keratinocytes - A genome-wide study in UVB irradiated organotypic 3D cultures.

PubMed

Rauhala, Leena; Hämäläinen, Lasse; Dunlop, Thomas W; Pehkonen, Petri; Bart, Geneviève; Kokkonen, Maarit; Tammi, Markku; Tammi, Raija; Pasonen-Seppänen, Sanna

2015-12-25

The moisturizing and potentially protective properties of the organic osmolyte betaine (trimethylglycine) have made it an attractive component for skin care products. Its wide use despite the lack of comprehensive studies addressing its specific effects in skin led us to characterize the molecular targets of betaine in keratinocytes and to explore, whether it modifies the effects of acute UVB exposure. Genome-wide expression analysis was performed on organotypic cultures of rat epidermal keratinocytes, treated either with betaine (10mM), UVB (30 mJ/cm(2)) or their combination. Results were verified with qRT-PCR, western blotting and immunohistochemistry. Additionally, cell proliferation and differentiation were analyzed. Among the 89 genes influenced by betaine, the differentiation marker keratin 2 showed the highest upregulation, which was also confirmed at protein level. Expression of Egr1, a transcription factor, and Purkinje cell protein 4, a regulator of Ca(2+)/calmodulin metabolism, also increased, while downregulated genes included several ion-channel components, such as Fxyd2. Bioinformatics analyses suggest that genes modulated by betaine are involved in DNA replication, might counteract UV-induced processes, and include many targets of transcription factors associated with cell proliferation and differentiation. Our results indicate that betaine controls unique gene expression pathways in keratinocytes, including some involved in differentiation. Copyright © 2015 Elsevier B.V. All rights reserved.

Disruption of SF3B1 results in deregulated expression and splicing of key genes and pathways in myelodysplastic syndrome hematopoietic stem and progenitor cells.

PubMed

Dolatshad, H; Pellagatti, A; Fernandez-Mercado, M; Yip, B H; Malcovati, L; Attwood, M; Przychodzen, B; Sahgal, N; Kanapin, A A; Lockstone, H; Scifo, L; Vandenberghe, P; Papaemmanuil, E; Smith, C W J; Campbell, P J; Ogawa, S; Maciejewski, J P; Cazzola, M; Savage, K I; Boultwood, J

2015-05-01

The splicing factor SF3B1 is the most commonly mutated gene in the myelodysplastic syndrome (MDS), particularly in patients with refractory anemia with ring sideroblasts (RARS). We investigated the functional effects of SF3B1 disruption in myeloid cell lines: SF3B1 knockdown resulted in growth inhibition, cell cycle arrest and impaired erythroid differentiation and deregulation of many genes and pathways, including cell cycle regulation and RNA processing. MDS is a disorder of the hematopoietic stem cell and we thus studied the transcriptome of CD34(+) cells from MDS patients with SF3B1 mutations using RNA sequencing. Genes significantly differentially expressed at the transcript and/or exon level in SF3B1 mutant compared with wild-type cases include genes that are involved in MDS pathogenesis (ASXL1 and CBL), iron homeostasis and mitochondrial metabolism (ALAS2, ABCB7 and SLC25A37) and RNA splicing/processing (PRPF8 and HNRNPD). Many genes regulated by a DNA damage-induced BRCA1-BCLAF1-SF3B1 protein complex showed differential expression/splicing in SF3B1 mutant cases. This is the first study to determine the target genes of SF3B1 mutation in MDS CD34(+) cells. Our data indicate that SF3B1 has a critical role in MDS by affecting the expression and splicing of genes involved in specific cellular processes/pathways, many of which are relevant to the known RARS pathophysiology, suggesting a causal link.

Evidence for a terminal differentiation process in the rat liver.

PubMed

Sigal, S H; Gupta, S; Gebhard, D F; Holst, P; Neufeld, D; Reid, L M

1995-07-01

In rapidly renewing epithelia, such as skin and gut, as well as hemopoietic cells and stromal fibroblasts, the process of progenitor cell maturation, terminal differentiation and senescence from cells of a fetal phenotype is strikingly similar. To examine hepatocellular maturation, we studied embryonic, suckling and young adult rat liver cells with multiparametric fluorescence activated cell sorting (FACS), after exclusion of hemopoietic, endothelial, Kupffer, and nonviable cells. With maturation, cell granularity and autofluorescence exponentially increased from fetal liver to suckling and adult liver as the proportion of S phase cells progressively declined from 33.8% +/- 1.3% to 4.9% +/- 2.8% and 1.1% +/- 0.6% (P < 0.05), respectively. In liver from fetal and suckling rats, all hepatocytes were mononuclear and contained diploid DNA whereas 21.2% +/- 5.9% hepatocytes in adult liver were binucleated. Analysis of nuclear DNA content in adult hepatocytes demonstrated that 53.3% +/- 3.9% of the nuclei were diploid, 43.6% +/- 3.5% tetraploid and 0.5 +/- 0.6% octaploid. However, in the adult liver, small, mononuclear cells were also present with granularity and autofluorescence comparable to fetal hepatoblasts, as well as glucose-6-phosphatase activity, diploid DNA in 89.0% +/- 2.1% of the nuclei, and with increased granularity in culture. Since general features of terminal cellularity differentiation and senescence include cessation of mitotic activity, polyploidy and accumulation of autofluorescent secondary lysosomes, our data suggest that liver cells too undergo a process of terminal differentiation.

Exploring the Mechanisms of Differentiation, Dedifferentiation, Reprogramming and Transdifferentiation

PubMed Central

Xu, Li; Zhang, Kun; Wang, Jin

2014-01-01

We explored the underlying mechanisms of differentiation, dedifferentiation, reprogramming and transdifferentiation (cell type switchings) from landscape and flux perspectives. Lineage reprogramming is a new regenerative method to convert a matured cell into another cell including direct transdifferentiation without undergoing a pluripotent cell state and indirect transdifferentiation with an initial dedifferentiation-reversion (reprogramming) to a pluripotent cell state. Each cell type is quantified by a distinct valley on the potential landscape with higher probability. We investigated three driving forces for cell fate decision making: stochastic fluctuations, gene regulation and induction, which can lead to cell type switchings. We showed that under the driving forces the direct transdifferentiation process proceeds from a differentiated cell valley to another differentiated cell valley through either a distinct stable intermediate state or a certain series of unstable indeterminate states. The dedifferentiation process proceeds through a pluripotent cell state. Barrier height and the corresponding escape time from the valley on the landscape can be used to quantify the stability and efficiency of cell type switchings. We also uncovered the mechanisms of the underlying processes by quantifying the dominant biological paths of cell type switchings on the potential landscape. The dynamics of cell type switchings are determined by both landscape gradient and flux. The flux can lead to the deviations of the dominant biological paths for cell type switchings from the naively expected landscape gradient path. As a result, the corresponding dominant paths of cell type switchings are irreversible. We also classified the mechanisms of cell fate development from our landscape theory: super-critical pitchfork bifurcation, sub-critical pitchfork bifurcation, sub-critical pitchfork with two saddle-node bifurcation, and saddle-node bifurcation. Our model showed good agreements with the experiments. It provides a general framework to explore the mechanisms of differentiation, dedifferentiation, reprogramming and transdifferentiation. PMID:25133589

Differential-Integral method in polymer processing: Taking melt electrospinning technique for example

NASA Astrophysics Data System (ADS)

Haoyi, Li; Weimin, Yang; Hongbo, Chen; Jing, Tan; Pengcheng, Xie

2016-03-01

A concept of Differential-Integral (DI) method applied in polymer processing and molding was proposed, which included melt DI injection molding, DI nano-composites extrusion molding and melt differential electrospinning principle and equipment. Taking the melt differential electrospinning for example to introduce the innovation research progress, two methods preparing polymer ultrafine fiber have been developed: solution electro-spinning and melt electro-spinning, between which solution electro-spinning is much simpler to realize in lab. More than 100 institutions have endeavored to conduct research on it and more than 30 thousand papers have been published. However, its industrialization was restricted to some extend because of the existence of toxic solvent during spinning process and poor mechanical strength of resultant fibers caused by small pores on fiber surface. Solvent-free melt electrospinning is environmentally friendly and highly productive. However, problems such as the high melt viscosity, thick fiber diameter and complex equipment makes it relatively under researched compared with solution electrospinning. With the purpose of solving the shortage of traditional electro-spinning equipment with needles or capillaries, a melt differential electro-spinning method without needles or capillaries was firstly proposed. Nearly 50 related patents have been applied since 2005, and systematic method innovations and experimental studies have also been conducted. The prepared fiber by this method had exhibited small diameter and smooth surface. The average fiber diameter can reach 200-800 nm, and the single nozzle can yield two orders of magnitude more than the capillaries. Based on the above principle, complete commercial techniques and equipment have been developed to produce ultra-fine non-woven fabrics for the applications in air filtration, oil spill recovery and water treatment, etc.

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.

Transcriptome profiling of the floating-leaved aquatic plant Nymphoides peltata in response to flooding stress.

PubMed

Wu, Jinwei; Zhao, Hua-Bin; Yu, Dan; Xu, Xinwei

2017-01-31

Waterlogging or flooding is one of the most challenging abiotic stresses experienced by plants. Unlike many flooding-tolerant plants, floating-leaved aquatic plants respond actively to flooding stress by fast growth and elongation of its petioles to make leaves re-floating. However, the molecular mechanisms of this plant group responding to flood have not been investigated before. Here, we investigated the genetic basis of this adaptive response by characterizing the petiole transcriptomes of a floating-leaved species Nymphoides peltata under normal and flooding conditions. Clean reads under normal and flooding conditions with pooled sampling strategy were assembled into 124,302 unigenes. A total of 8883 unigenes were revealed to be differentially expressed between normal and flooding conditions. Among them, top ranked differentially expressed genes were mainly involved in antioxidant process, photosynthesis process and carbohydrate metabolism, including the glycolysis and a modified tricarboxylic acid cycle - alanine metabolism. Eight selected unigenes with significantly differentiated expression changes between normal and flooding conditions were validated by qRT-PCR. Among these processes, antioxidant process and glycolysis are commonly induced by waterlogging or flooding environment in plants, whereas photosynthesis and alanine metabolism are rarely occurred in other flooding-tolerant plants, suggesting the significant contributions of the two processes in the active response of N. peltata to flooding stress. Our results provide a valuable genomic resource for future studies on N. peltata and deepen our understanding of the genetic basis underlying the response to flooding stress in aquatic plants.

SPARTA: Simple Program for Automated reference-based bacterial RNA-seq Transcriptome Analysis.

PubMed

Johnson, Benjamin K; Scholz, Matthew B; Teal, Tracy K; Abramovitch, Robert B

2016-02-04

Many tools exist in the analysis of bacterial RNA sequencing (RNA-seq) transcriptional profiling experiments to identify differentially expressed genes between experimental conditions. Generally, the workflow includes quality control of reads, mapping to a reference, counting transcript abundance, and statistical tests for differentially expressed genes. In spite of the numerous tools developed for each component of an RNA-seq analysis workflow, easy-to-use bacterially oriented workflow applications to combine multiple tools and automate the process are lacking. With many tools to choose from for each step, the task of identifying a specific tool, adapting the input/output options to the specific use-case, and integrating the tools into a coherent analysis pipeline is not a trivial endeavor, particularly for microbiologists with limited bioinformatics experience. To make bacterial RNA-seq data analysis more accessible, we developed a Simple Program for Automated reference-based bacterial RNA-seq Transcriptome Analysis (SPARTA). SPARTA is a reference-based bacterial RNA-seq analysis workflow application for single-end Illumina reads. SPARTA is turnkey software that simplifies the process of analyzing RNA-seq data sets, making bacterial RNA-seq analysis a routine process that can be undertaken on a personal computer or in the classroom. The easy-to-install, complete workflow processes whole transcriptome shotgun sequencing data files by trimming reads and removing adapters, mapping reads to a reference, counting gene features, calculating differential gene expression, and, importantly, checking for potential batch effects within the data set. SPARTA outputs quality analysis reports, gene feature counts and differential gene expression tables and scatterplots. SPARTA provides an easy-to-use bacterial RNA-seq transcriptional profiling workflow to identify differentially expressed genes between experimental conditions. This software will enable microbiologists with limited bioinformatics experience to analyze their data and integrate next generation sequencing (NGS) technologies into the classroom. The SPARTA software and tutorial are available at sparta.readthedocs.org.

Multitrait successional forest dynamics enable diverse competitive coexistence

PubMed Central

Brännström, Åke; Westoby, Mark; Dieckmann, Ulf

2017-01-01

To explain diversity in forests, niche theory must show how multiple plant species coexist while competing for the same resources. Although successional processes are widespread in forests, theoretical work has suggested that differentiation in successional strategy allows only a few species stably to coexist, including only a single shade tolerant. However, this conclusion is based on current niche models, which encode a very simplified view of plant communities, suggesting that the potential for niche differentiation has remained unexplored. Here, we show how extending successional niche models to include features common to all vegetation—height-structured competition for light under a prevailing disturbance regime and two trait-mediated tradeoffs in plant function—enhances the diversity of species that can be maintained, including a diversity of shade tolerants. We identify two distinct axes of potential niche differentiation, corresponding to the traits leaf mass per unit leaf area and height at maturation. The first axis allows for coexistence of different shade tolerances and the second axis for coexistence among species with the same shade tolerance. Addition of this second axis leads to communities with a high diversity of shade tolerants. Niche differentiation along the second axis also generates regions of trait space wherein fitness is almost equalized, an outcome we term “evolutionarily emergent near-neutrality.” For different environmental conditions, our model predicts diverse vegetation types and trait mixtures, akin to observations. These results indicate that the outcomes of successional niche differentiation are richer than previously thought and potentially account for mixtures of traits and species observed in forests worldwide. PMID:28283658

Differential gene expression analysis in glioblastoma cells and normal human brain cells based on GEO database.

PubMed

Wang, Anping; Zhang, Guibin

2017-11-01

The differentially expressed genes between glioblastoma (GBM) cells and normal human brain cells were investigated to performed pathway analysis and protein interaction network analysis for the differentially expressed genes. GSE12657 and GSE42656 gene chips, which contain gene expression profile of GBM were obtained from Gene Expression Omniub (GEO) database of National Center for Biotechnology Information (NCBI). The 'limma' data packet in 'R' software was used to analyze the differentially expressed genes in the two gene chips, and gene integration was performed using 'RobustRankAggreg' package. Finally, pheatmap software was used for heatmap analysis and Cytoscape, DAVID, STRING and KOBAS were used for protein-protein interaction, Gene Ontology (GO) and KEGG analyses. As results: i) 702 differentially expressed genes were identified in GSE12657, among those genes, 548 were significantly upregulated and 154 were significantly downregulated (p<0.01, fold-change >1), and 1,854 differentially expressed genes were identified in GSE42656, among the genes, 1,068 were significantly upregulated and 786 were significantly downregulated (p<0.01, fold-change >1). A total of 167 differentially expressed genes including 100 upregulated genes and 67 downregulated genes were identified after gene integration, and the genes showed significantly different expression levels in GBM compared with normal human brain cells (p<0.05). ii) Interactions between the protein products of 101 differentially expressed genes were identified using STRING and expression network was established. A key gene, called CALM3, was identified by Cytoscape software. iii) GO enrichment analysis showed that differentially expressed genes were mainly enriched in 'neurotransmitter:sodium symporter activity' and 'neurotransmitter transporter activity', which can affect the activity of neurotransmitter transportation. KEGG pathway analysis showed that the differentially expressed genes were mainly enriched in 'protein processing in endoplasmic reticulum', which can affect protein processing in endoplasmic reticulum. The results showed that: i) 167 differentially expressed genes were identified from two gene chips after integration; and ii) protein interaction network was established, and GO and KEGG pathway analyses were successfully performed to identify and annotate the key gene, which provide new insights for the studies on GBN at gene level.

Processes and Stages of Differentiation in European Higher Education

ERIC Educational Resources Information Center

Goglio, Valentina; Regini, Marino

2017-01-01

In this article we discuss processes of internal differentiation that have characterised European higher education systems in the last 50 years. We argue that these processes have gone through two main stages and in two different directions, each of which is showing its limits in the long run. Therefore, we expect a third stage of differentiation,…

Video image processing greatly enhances contrast, quality, and speed in polarization-based microscopy

PubMed Central

1981-01-01

Video cameras with contrast and black level controls can yield polarized light and differential interference contrast microscope images with unprecedented image quality, resolution, and recording speed. The theoretical basis and practical aspects of video polarization and differential interference contrast microscopy are discussed and several applications in cell biology are illustrated. These include: birefringence of cortical structures and beating cilia in Stentor, birefringence of rotating flagella on a single bacterium, growth and morphogenesis of echinoderm skeletal spicules in culture, ciliary and electrical activity in a balancing organ of a nudibranch snail, and acrosomal reaction in activated sperm. PMID:6788777

miR-383 negatively regulates osteoblastic differentiation of bone marrow mesenchymal stem cells in rats by targeting Satb2.

PubMed

Tang, Jianfei; Zhang, Zeng; Jin, Xiangyun; Shi, Huipeng

2018-06-14

Emerging evidence indicates that microRNAs (miRNAs, miRs) play diverse roles in the regulation of biological processes, including osteoblastic differentiation. In this study, we found that miR-383 is a critical regulator of osteoblastic differentiation. We showed that miR-383 was downregulated during osteoblastic differentiation of rat bone marrow mesenchymal stem cells (BMSCs). Overexpression of miR-383 suppressed osteoblastic differentiation of BMSCs by downregulating alkaline phosphatase (ALP), matrix mineralization, and mRNA and protein levels of RUNX2 and OCN, whereas a knockdown of miR-383 promoted osteoblastic differentiation in vitro. The results of in vivo analysis indicated that inhibition of miR-383 expression enhanced the efficacy of new bone formation in a rat calvarial defect model. Mechanistic experiments revealed that special AT-rich-sequence-binding protein 2 (Satb2) was a direct and functional target of miR-383. Knockdown of Satb2 had inhibitory effects resembling those of miR-383 on the osteoblast differentiation of rat BMSCs. In addition, the positive effect of miR-383 suppression on osteoblastic differentiation was apparently abrogated by Satb2 silencing. Collectively, these results indicate that miR-383 plays an inhibitory role in osteogenic differentiation of rat BMSCs and may act by targeting Satb2. Copyright © 2017. Published by Elsevier Inc.

Diverse functions of miR-17-92 cluster microRNAs in T helper cells.

PubMed

Baumjohann, Dirk

2018-06-01

T helper (Th) cells are critically involved in adaptive immune responses against various pathogens. In contrast, dysregulated T helper cell responses are associated with a variety of diseases, including autoimmunity, allergies, and cancer. Differentiation of naïve CD4 + T cells into effector T helper cell subsets, including Th1, Th2, Th17, Treg, and T follicular helper (Tfh), requires precise dosing of signaling molecules and transcription factors. MicroRNAs (miRNAs), which are small endogenously expressed RNAs that regulate gene expression, play important roles in these processes. The miR-17-92 cluster, a miRNA polycistron also known as oncomiR-1, has emerged as a central integrator of gene expression events that govern T helper cell differentiation pathways. The complexity of miR-17-92-mediated gene regulation lies in the nature of this miRNA cluster, which consists of six different miRNAs. Individual miR-17-92 miRNAs, albeit initially transcribed as one transcript, can have cooperative or opposing effects on biological processes. Therefore, a better understanding of the molecular regulation of miR-17-92 and its downstream networks will provide important insights into T helper cell differentiation and diversity that may be harnessed for the design of advanced T cell-targeting therapies. Copyright © 2018 Elsevier B.V. All rights reserved.

Differentiated muscles are mandatory for gas-filling of the Drosophila airway system.

PubMed

Wang, Yiwen; Cruz, Tina; Irion, Uwe; Moussian, Bernard

2015-11-30

At the end of development, organs acquire functionality, thereby ensuring autonomy of an organism when it separates from its mother or a protective egg. In insects, respiratory competence starts when the tracheal system fills with gas just before hatching of the juvenile animal. Cellular and molecular mechanisms of this process are not fully understood. Analyses of the phenotype of Drosophila embryos with malformed muscles revealed that they fail to gas-fill their tracheal system. Indeed, we show that major regulators of muscle formation like Lame duck and Blown fuse are important, while factors involved in the development of subsets of muscles including cardiac and visceral muscles are dispensable for this process, suggesting that somatic muscles (or parts of them) are essential to enable tracheal terminal differentiation. Based on our phenotypic data, we assume that somatic muscle defect severity correlates with the penetrance of the gas-filling phenotype. This argues that a limiting molecular or mechanical muscle-borne signal tunes tracheal differentiation. We think that in analogy to the function of smooth muscles in vertebrate lungs, a balance of physical forces between muscles and the elasticity of tracheal walls may be decisive for tracheal terminal differentiation in Drosophila. © 2015. Published by The Company of Biologists Ltd.

Proliferation and osteogenic differentiation of rat BMSCs on a novel Ti/SiC metal matrix nanocomposite modified by friction stir processing

NASA Astrophysics Data System (ADS)

Zhu, Chenyuan; Lv, Yuting; Qian, Chao; Qian, Haixin; Jiao, Ting; Wang, Liqiang; Zhang, Fuqiang

2016-12-01

The aims of this study were to fabricate a novel titanium/silicon carbide (Ti/SiC) metal matrix nanocomposite (MMNC) by friction stir processing (FSP) and to investigate its microstructure and mechanical properties. In addition, the adhesion, proliferation and osteogenic differentiation of rat bone marrow stromal cells (BMSCs) on the nanocomposite surface were investigated. The MMNC microstructure was observed by both scanning and transmission electron microscopy. Mechanical properties were characterized by nanoindentation and Vickers hardness testing. Integrin β1 immunofluorescence, cell adhesion, and MTT assays were used to evaluate the effects of the nanocomposite on cell adhesion and proliferation. Osteogenic and angiogenic differentiation were evaluated by alkaline phosphatase (ALP) staining, ALP activity, PCR and osteocalcin immunofluorescence. The observed microstructures and mechanical properties clearly indicated that FSP is a very effective technique for modifying Ti/SiC MMNC to contain uniformly distributed nanoparticles. In the interiors of recrystallized grains, characteristics including twins, fine recrystallized grains, and dislocations formed concurrently. Adhesion, proliferation, and osteogenic and angiogenic differentiation of rat BMSCs were all enhanced on the novel Ti/SiC MMNC surface. In conclusion, nanocomposites modified using FSP technology not only have superior mechanical properties under stress-bearing conditions but also provide improved surface and physicochemical properties for cell attachment and osseointegration.

Three-dimensional co-culture process

NASA Technical Reports Server (NTRS)

Wolf, David A. (Inventor); Goodwin, Thomas J. (Inventor)

1992-01-01

The present invention relates to a 3-dimensional co-culture process, more particularly to methods or co-culturing at least two types of cells in a culture environment, either in space or in unit gravity, with minimum shear stress, freedom for 3-dimensional spatial orientation of the suspended particles and localization of particles with differing or similar sedimentation properties in a similar spatial region to form 3-dimensional tissue-like structures. Several examples of multicellular 3-dimensional experiences are included. The protocol and procedure are also set forth. The process allows simultaneous culture of multiple cell types and supporting substrates in a manner which does not disrupt the 3-dimensional spatial orientation of these components. The co-cultured cells cause a mutual induction effect which mimics the natural hormonal signals and cell interactions found in the intact organism. This causes the tissues to differentiate and form higher 3-dimensional structures such as glands, junctional complexes polypoid geometries, and microvilli which represent the corresponding in-vitro structures to a greater degree than when the cell types are cultured individually or by conventional processes. This process was clearly demonstrated for the case of two epithelial derived colon cancer lines, each co-cultured with normal human fibroblasts and with microcarrier bead substrates. The results clearly demonstrate increased 3-dimensional tissue-like structure and biochemical evidence of an increased differentiation state. With the present invention a variety of cells may be co-cultured to produce tissue which has 3-dimensionality and has some of the characteristics of in-vitro tissue. The process provides enhanced 3-dimensional tissue which create a multicellular organoid differentiation model.

Application of 5-ALA for differential diagnostics of stomach diseases

NASA Astrophysics Data System (ADS)

Okhotnikova, Natalja L.; Dadvany, Sergey A.; Kuszin, Michail I.; Kharnas, Sergey S.; Zavodnov, Victor Y.; Sklyanskaya, Olga A.; Loschenov, Victor B.; Volkova, Anna I.; Agafonov, Valery V.

2001-01-01

59 patients with stomach diseases including gastric cancer or polyp, gastritis, esofagus disease were investigated. Before gastroscopy all patients were given 5-ALA in doses 5mg, 10mg and 20mg per 1kg of body weight orally. Fluorescence diagnostics which estimates concentration of ALA-induced PPIX in regular and alternated tissues of gastric mucosa were carried out in 2-4 hours. Using of 5-ALA has shown high diagnostic effectiveness for differential diagnostics of stomach diseases. This technique has proved 10 diagnosis of cancer and revealed 15 malignant stomach diseases including 4 cancer in situ for patients with preliminary diagnosis of gastric ulcer. It also revealed 5 patients with enhanced fluorescence for which aimed biopsy has shown high degree of inflammation process. The latter were assigned as a risk group.

Neural mechanisms of attentional control differentiate trait and state negative affect.

PubMed

Crocker, Laura D; Heller, Wendy; Spielberg, Jeffrey M; Warren, Stacie L; Bredemeier, Keith; Sutton, Bradley P; Banich, Marie T; Miller, Gregory A

2012-01-01

The present research examined the hypothesis that cognitive processes are modulated differentially by trait and state negative affect (NA). Brain activation associated with trait and state NA was measured by fMRI during an attentional control task, the emotion-word Stroop. Performance on the task was disrupted only by state NA. Trait NA was associated with reduced activity in several regions, including a prefrontal area that has been shown to be involved in top-down, goal-directed attentional control. In contrast, state NA was associated with increased activity in several regions, including a prefrontal region that has been shown to be involved in stimulus-driven aspects of attentional control. Results suggest that NA has a significant impact on cognition, and that state and trait NA disrupt attentional control in distinct ways.

D-A type sensor array for differentiation and identification of white wine varieties based on specific solvent effect activated by CT-LE transition

NASA Astrophysics Data System (ADS)

Han, Jingqi; Zhang, Xin; Li, Hao; Hou, Yue; Hou, Jingdan; Li, Zhongfeng; Yang, Feng; Liu, Yang; Han, Tianyu

2018-02-01

In this work, we synthesize a series of compounds with electron donor (D) and acceptor (A) units. They show general solvent effect in aprotic solvents, suggesting a charge transfer (CT) process. While in protic solvents including water, ethanol and methanol, the spectra exert no polarity-dependence but a remarkable hypochromatic shift together with the fading of CT band. Dynamic analysis implies that intermolecular hydrogen bond will be formed between carboxylic acid and protic solvent, boosting another deactivation pathway that jumps off a bigger energy gap, in other words, favoring the locally excited (LE) state emission. The CT-LE transition involves variations in both absorption and emission spectra, and further poses competition with other mechanisms including activated/restricted intramolecular rotation (IR/RIR). Inspired by the cross-reactivity, we turn our attention to the development of sensor array, in order to identify white wine varieties. The differential spectral responses are recorded, generating multiple factors including absorption wavelength (λab), emission wavelength (λem), absorbance (Abs.) and emission intensity (Int.). These factors are processed with principal component analysis (PCA), creating a three-dimensional fingerprint data base for white wines. The data points in the coordinate system are clustered into 10 different groups, demonstrating a clear differentiation of all the white wines. More importantly, as our final test for whether the sensor array can identify the counterfeits, an adulterated liquor sample, which is provided by police officers, is fingerprinted on the three-dimensional diagram. Its canonical factors fall into an area distinct from the adulterated wine, indicating a clear identification.

Process-Based Expansion and Neural Differentiation of Human Pluripotent Stem Cells for Transplantation and Disease Modeling

PubMed Central

Stover, Alexander E.; Brick, David J.; Nethercott, Hubert E.; Banuelos, Maria G.; Sun, Lei; O’Dowd, Diane K.; Schwartz, Philip H.

2014-01-01

Robust strategies for developing patient-specific, human, induced pluripotent stem cell (iPSC)-based therapies of the brain require an ability to derive large numbers of highly defined neural cells. Recent progress in iPSC culture techniques includes partial-to-complete elimination of feeder layers, use of defined media, and single-cell passaging. However, these techniques still require embryoid body formation or coculture for differentiation into neural stem cells (NSCs). In addition, none of the published methodologies has employed all of the advances in a single culture system. Here we describe a reliable method for long-term, single-cell passaging of PSCs using a feeder-free, defined culture system that produces confluent, adherent PSCs that can be differentiated into NSCs. To provide a basis for robust quality control, we have devised a system of cellular nomenclature that describes an accurate genotype and phenotype of the cells at specific stages in the process. We demonstrate that this protocol allows for the efficient, large-scale, cGMP-compliant production of transplantable NSCs from all lines tested. We also show that NSCs generated from iPSCs produced with the process described are capable of forming both glia defined by their expression of S100β and neurons that fire repetitive action potentials. PMID:23893392

Sensory reactivity, empathizing and systemizing in autism spectrum conditions and sensory processing disorder.

PubMed

Tavassoli, Teresa; Miller, Lucy Jane; Schoen, Sarah A; Jo Brout, Jennifer; Sullivan, Jillian; Baron-Cohen, Simon

2018-01-01

Although the DSM-5 added sensory symptoms as a criterion for ASC, there is a group of children who display sensory symptoms but do not have ASC; children with sensory processing disorder (SPD). To be able to differentiate these two disorders, our aim was to evaluate whether children with ASC show more sensory symptomatology and/or different cognitive styles in empathy and systemizing compared to children with SPD and typically developing (TD) children. The study included 210 participants: 68 children with ASC, 79 with SPD and 63 TD children. The Sensory Processing Scale Inventory was used to measure sensory symptoms, the Autism Spectrum Quotient (AQ) to measure autistic traits, and the Empathy Quotient (EQ) and Systemizing Quotient (SQ) to measure cognitive styles. Across groups, a greater sensory symptomatology was associated with lower empathy. Further, both the ASC and SPD groups showed more sensory symptoms than TD children. Children with ASC and SPD only differed on sensory under-reactivity. The ASD group did, however, show lower empathy and higher systemizing scores than the SPD group. Together, this suggest that sensory symptoms alone may not be adequate to differentiate children with ASC and SPD but that cognitive style measures could be used for differential diagnosis. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Marriage and health: his and hers.

PubMed

Kiecolt-Glaser, J K; Newton, T L

2001-07-01

This review focuses on the pathway leading from the marital relationship to physical health. Evidence from 64 articles published in the past decade, particularly marital interaction studies, suggests that marital functioning is consequential for health; negative dimensions of marital functioning have indirect influences on health outcomes through depression and health habits, and direct influences on cardiovascular, endocrine, immune, neurosensory, and other physiological mechanisms. Moreover, individual difference variables such as trait hostility augment the impact of marital processes on biological systems. Emerging themes in the past decade include the importance of differentiating positive and negative dimensions of marital functioning, the explanatory power of behavioral data, and gender differences in the pathways from the marital relationship to physiological functioning. Contemporary models of gender that emphasize self-processes, traits, and roles furnish alternative perspectives on the differential costs and benefits of marriage for men's and women's health.

Roles of mTOR Signaling in Brain Development.

PubMed

Lee, Da Yong

2015-09-01

mTOR is a serine/threonine kinase composed of multiple protein components. Intracellular signaling of mTOR complexes is involved in many of physiological functions including cell survival, proliferation and differentiation through the regulation of protein synthesis in multiple cell types. During brain development, mTOR-mediated signaling pathway plays a crucial role in the process of neuronal and glial differentiation and the maintenance of the stemness of neural stem cells. The abnormalities in the activity of mTOR and its downstream signaling molecules in neural stem cells result in severe defects of brain developmental processes causing a significant number of brain disorders, such as pediatric brain tumors, autism, seizure, learning disability and mental retardation. Understanding the implication of mTOR activity in neural stem cells would be able to provide an important clue in the development of future brain developmental disorder therapies.

Neutral dynamics and cell renewal of colonic crypts in homeostatic regime

NASA Astrophysics Data System (ADS)

Fendrik, A. J.; Romanelli, L.; Rotondo, E.

2018-05-01

The self renewal process in colonic crypts is the object of several studies. We present here a new compartment model with the following characteristics: (a) we distinguish different classes of cells: stem cells, six generations of transit amplifying cells and the differentiated cells; (b) in order to take into account the monoclonal character of crypts in homeostatic regimes we include symmetric divisions of the stem cells. We first consider the dynamic differential equations that describe the evolution of the mean values of the populations, but the small observed value of the total number of cells involved plus the huge dispersion of experimental data found in the literature leads us to study the stochastic discrete process. This analysis allows us to study fluctuations, the neutral drift that leads to monoclonality, and the effects of the fixation of mutant clones.

Early events in geotropism of seedling shoots

NASA Technical Reports Server (NTRS)

Pickard, B. G.

1985-01-01

Developments during the first ten minutes of geotropic stimulation in plant seedling shoots are reviewed. Topics include induction and curvature; early processes; the relationship between auxin, electric field, calcium, and differential growth; gravity reception leading to Went-Cholodny transport; and comparison of root and shoot. Early processes reviewed are sedimentation of amyloplasts, release of ethylene, rise of electrical and auxin asymmetry, redistribution of calcium, asymmetric vascular transport, increase in tendency to deposit callose, and simulation of putative exocytotic voltage transients.

[Progress of study on the detection technique of microRNA].

PubMed

Zhao, Hai-Feng; Yang, Ren-Chi

2009-12-01

MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate gene expression via degradation or translational repression of their targeted mRNAs. MiRNAs are involved in critical biologic processes, including development, cell differentiation, proliferation and the pathogenesis of disease. This review focuses on recent researches on the detection techniques of miRNA including micorarray technique, Northern blot, real-time quantitative PCR, detection technique of miRNA function and so on.

Stochastic differential equations and turbulent dispersion

NASA Technical Reports Server (NTRS)

Durbin, P. A.

1983-01-01

Aspects of the theory of continuous stochastic processes that seem to contribute to an understanding of turbulent dispersion are introduced and the theory and philosophy of modelling turbulent transport is emphasized. Examples of eddy diffusion examined include shear dispersion, the surface layer, and channel flow. Modeling dispersion with finite-time scale is considered including the Langevin model for homogeneous turbulence, dispersion in nonhomogeneous turbulence, and the asymptotic behavior of the Langevin model for nonhomogeneous turbulence.

[Fibroblast growth factors and their effects in pancreas organogenesis].

PubMed

Gnatenko, D A; Kopantzev, E P; Sverdlov, E D

2017-05-01

Fibroblast growth factors (FGF) - growth factors that regulate many important biological processes, including proliferation and differentiation of embryonic cells during organogenesis. In this review, we will summarize current information about the involvement of FGFs in the pancreas organogenesis. Pancreas organogenesis is a complex process, which involves constant signaling from mesenchymal tissue. This orchestrates the activation of various regulator genes at specific stages, determining the specification of progenitor cells. Alterations in FGF/FGFR signaling pathway during this process lead to incorrect activation of the master genes, which leads to different pathologies during pancreas development. Understanding the full picture about role of FGF factors in pancreas development will make it possible to more accurately understand their role in other pathologies of this organ, including carcinogenesis.

Quantifying Cell Fate Decisions for Differentiation and Reprogramming of a Human Stem Cell Network: Landscape and Biological Paths

PubMed Central

Li, Chunhe; Wang, Jin

2013-01-01

Cellular reprogramming has been recently intensively studied experimentally. We developed a global potential landscape and kinetic path framework to explore a human stem cell developmental network composed of 52 genes. We uncovered the underlying landscape for the stem cell network with two basins of attractions representing stem and differentiated cell states, quantified and exhibited the high dimensional biological paths for the differentiation and reprogramming process, connecting the stem cell state and differentiated cell state. Both the landscape and non-equilibrium curl flux determine the dynamics of cell differentiation jointly. Flux leads the kinetic paths to be deviated from the steepest descent gradient path, and the corresponding differentiation and reprogramming paths are irreversible. Quantification of paths allows us to find out how the differentiation and reprogramming occur and which important states they go through. We show the developmental process proceeds as moving from the stem cell basin of attraction to the differentiation basin of attraction. The landscape topography characterized by the barrier heights and transition rates quantitatively determine the global stability and kinetic speed of cell fate decision process for development. Through the global sensitivity analysis, we provided some specific predictions for the effects of key genes and regulation connections on the cellular differentiation or reprogramming process. Key links from sensitivity analysis and biological paths can be used to guide the differentiation designs or reprogramming tactics. PMID:23935477

Identification of genes differentially expressed during interaction of resistant and susceptible apple cultivars (Malus x domestica) with Erwinia amylovora

USDA-ARS?s Scientific Manuscript database

The necrogenic enterobacterium, Erwinia amylovora is the causal agent of the fire blight (FB) disease in many Rosaceae species, including apple and pear. During the infection process, the bacteria induce an oxidative stress response with kinetics similar to those induced in an incompatible bacteria-...

The Hippocampus Supports Encoding of Between-Domain Associations within Working Memory

ERIC Educational Resources Information Center

Piekema, Carinne; Kessel, Roy P. C.; Rijpkema, Mark; Fernandez, Guillen

2009-01-01

It has been established that the medial temporal lobe, including the hippocampus, is crucial for associative memory. The aim of the current functional magnetic resonance imaging (fMRI) study was to investigate whether the hippocampus is differentially activated for associations between items processed in the same neocortical region (within-domain)…

Surfacing the Depths: Thoughts on Imitation, Resonance and Growth

ERIC Educational Resources Information Center

Music, Graham

2005-01-01

This paper examines some of the research on imitation that shows it to be much more than simply a behavioural or reflex response, but rather an aspect of the growth of genuine social and psychological interaction and part of an intersubjective process that includes the representation of object relationships. Differentiations between mind,…

Differential expression in Phanerochaete chrysosporium of membrane- associated proteins relevant to lignin degradation

Treesearch

Semarjit Shary; Alexander N. Kapich; Ellen A. Panisko; Jon K. Magnuson; Daniel Cullen; Kenneth E. Hammel

2008-01-01

Fungal lignin-degrading systems likely include membrane-associated proteins that participate in diverse processes such as uptake and oxidation of lignin fragments, production of ligninolytic secondary metabolites, and defense of the mycelium against ligninolytic oxidants. Little is known about the nature or regulation of these membrane-associated components. We grew...

3D-QSAR Study of Steroidal and Azaheterocyclic Human Aromatase Inhibitors using Quantitative Profile of Protein-Ligand Interactions

EPA Science Inventory

Aromatase is a member of the cytochrome P450 superfamily responsible for a key step in the biosynthesis of estrogens. As estrogens are involved in the control of important reproduction-related processes, including sexual differentiation and maturation, aromatase is a potential ta...

Switching from Reaching to Navigation: Differential Cognitive Strategies for Spatial Memory in Children and Adults

ERIC Educational Resources Information Center

Belmonti, Vittorio; Cioni, Giovanni; Berthoz, Alain

2015-01-01

Navigational and reaching spaces are known to involve different cognitive strategies and brain networks, whose development in humans is still debated. In fact, high-level spatial processing, including allocentric location encoding, is already available to very young children, but navigational strategies are not mature until late childhood. The…

From Children's Perspectives: A Model of Aesthetic Processing in Theatre

ERIC Educational Resources Information Center

Klein, Jeanne

2005-01-01

While several developmental models of aesthetic understanding, experience, and appreciation exist in the realms of visual art and music education, few examples have been proposed in regard to theatre, particularly for child audiences. This author argues that children gaze upon theatre in differential ways by including age as a variable…

Molecular Programs Underlying Asymmetric Stem Cell Division and Their Disruption in Malignancy.

PubMed

Mukherjee, Subhas; Brat, Daniel J

2017-01-01

Asymmetric division of stem cells is a highly conserved and tightly regulated process by which a single stem cell produces two unequal daughter cells. One retains its stem cell identity while the other becomes specialized through a differentiation program and loses stem cell properties. Coordinating these events requires control over numerous intra- and extracellular biological processes and signaling networks. In the initial stages, critical events include the compartmentalization of fate determining proteins within the mother cell and their subsequent passage to the appropriate daughter cell in order to direct their destiny. Disturbance of these events results in an altered dynamic of self-renewing and differentiation within the cell population, which is highly relevant to the growth and progression of cancer. Other critical events include proper asymmetric spindle assembly, extrinsic regulation through micro-environmental cues, and non-canonical signaling networks that impact cell division and fate determination. In this review, we discuss mechanisms that maintain the delicate balance of asymmetric cell division in normal tissues and describe the current understanding how some of these mechanisms are deregulated in cancer.

Differential gene expression between skin and cervix induced by the E7 oncoprotein in a transgenic mouse model

PubMed Central

Ibarra Sierra, E; Díaz Chávez, J; Cortés-Malagón, EM; Uribe-Figueroa, L; Hidalgo-Miranda, A; Lambert, PF; Gariglio, P

2013-01-01

HPV16 E7 oncoprotein expression in K14E7 transgenic mice induces cervical cancer after 6 months of treatment with the co-carcinogen 17β-estradiol. In untreated mice, E7 also induces skin tumors late in life albeit at low penetrance. These findings indicate that E7 alters cellular functions in cervix and skin so as to predispose these organs to tumorigenesis. Using microarrays, we determined the global genes expression profile in cervical and skin tissue of young adult K14E7 transgenic mice without estrogen treatment. In these tissues, the E7 oncoprotein altered the transcriptional pattern of genes involved in several biological processes including signal transduction, transport, metabolic process, cell adhesion, apoptosis, cell differentiation, immune response and inflammatory response. Among the E7-dysregulated genes were ones not previously known to be involved in cervical neoplasia including DMBT1, GLI1 and 17βHSD2 in cervix, as well as MMP2, 12, 14, 19 and 27 in skin. PMID:22980503

Differential gene expression between skin and cervix induced by the E7 oncoprotein in a transgenic mouse model.

PubMed

Ibarra Sierra, E; Díaz Chávez, J; Cortés-Malagón, E M; Uribe-Figueroa, L; Hidalgo-Miranda, A; Lambert, P F; Gariglio, P

2012-11-25

HPV16 E7 oncoprotein expression in K14E7 transgenic mice induces cervical cancer after 6 months of treatment with the co-carcinogen 17β-estradiol. In untreated mice, E7 also induces skin tumors late in life albeit at low penetrance. These findings indicate that E7 alters cellular functions in cervix and skin so as to predispose these organs to tumorigenesis. Using microarrays, we determined the global genes expression profile in cervical and skin tissue of young adult K14E7 transgenic mice without estrogen treatment. In these tissues, the E7 oncoprotein altered the transcriptional pattern of genes involved in several biological processes including signal transduction, transport, metabolic process, cell adhesion, apoptosis, cell differentiation, immune response and inflammatory response. Among the E7-dysregulated genes were ones not previously known to be involved in cervical neoplasia including DMBT1, GLI1 and 17βHSD2 in cervix, as well as MMP2, 12, 14, 19 and 27 in skin. Copyright © 2012 Elsevier Inc. All rights reserved.

Sleep inertia, sleep homeostatic, and circadian influences on higher-order cognitive functions

PubMed Central

Ronda, Joseph M.; Czeisler, Charles A.; Wright, Kenneth P.

2016-01-01

Summary Sleep inertia, sleep homeostatic, and circadian processes modulate cognition, including reaction time, memory, mood, and alertness. How these processes influence higher-order cognitive functions is not well known. Six participants completed a 73-daylong study that included two 14-daylong 28h forced desynchrony protocols, to examine separate and interacting influences of sleep inertia, sleep homeostasis, and circadian phase on higher-order cognitive functions of inhibitory control and selective visual attention. Cognitive performance for most measures was impaired immediately after scheduled awakening and improved over the first ~2-4h of wakefulness (sleep inertia); worsened thereafter until scheduled bedtime (sleep homeostasis); and was worst at ~60° and best at ~240° (circadian modulation, with worst and best phases corresponding to ~9AM and ~9PM respectively, in individuals with a habitual waketime of 7AM). The relative influences of sleep inertia, sleep homeostasis, and circadian phase depended on the specific higher-order cognitive function task examined. Inhibitory control appeared to be modulated most strongly by circadian phase, whereas selective visual attention for a spatial-configuration search task was modulated most strongly by sleep inertia. These findings demonstrate that some higher-order cognitive processes are differentially sensitive to different sleep-wake regulatory processes. Differential modulation of cognitive functions by different sleep-wake regulatory processes has important implications for understanding mechanisms contributing to performance impairments during adverse circadian phases, sleep deprivation, and/or upon awakening from sleep. PMID:25773686

Betaine supplement enhances skeletal muscle differentiation in murine myoblasts via IGF-1 signaling activation.

PubMed

Senesi, Pamela; Luzi, Livio; Montesano, Anna; Mazzocchi, Nausicaa; Terruzzi, Ileana

2013-07-19

Betaine (BET) is a component of many foods, including spinach and wheat. It is an essential osmolyte and a source of methyl groups. Recent studies have hypothesized that BET might play a role in athletic performance. However, BET effects on skeletal muscle differentiation and hypertrophy are still poorly understood. We examined BET action on neo myotubes maturation and on differentiation process, using C2C12 murine myoblastic cells. We used RT2-PCR array, Western blot and immunofluorescence analysis to study the BET effects on morphological features of C2C12 and on signaling pathways involved in muscle differentiation and hypertrophy. We performed a dose-response study, establishing that 10 mM BET was the dose able to stimulate morphological changes and hypertrophic process in neo myotubes. RT2-PCR array methodology was used to identify the expression profile of genes encoding proteins involved in IGF-1 pathway. A dose of 10 mM BET was found to promote IGF-1 receptor (IGF-1 R) expression. Western blot and immunofluorescence analysis, performed in neo myotubes, pointed out that 10 mM BET improved IGF-1 signaling, synthesis of Myosin Heavy Chain (MyHC) and neo myotubes length. Our findings provide the first evidence that BET could promote muscle fibers differentiation and increase myotubes size by IGF-1 pathway activation, suggesting that BET might represent a possible new drug/integrator strategy, not only in sport performance but also in clinical conditions characterized by muscle function impairment.

Gene expression profiling in multipotent DFAT cells derived from mature adipocytes

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

Ono, Hiromasa; Database Center for Life Science; Oki, Yoshinao

2011-04-15

Highlights: {yields} Adipocyte dedifferentiation is evident in a significant decrease in typical genes. {yields} Cell proliferation is strongly related to adipocyte dedifferentiation. {yields} Dedifferentiated adipocytes express several lineage-specific genes. {yields} Comparative analyses using publicly available datasets boost the interpretation. -- Abstract: Cellular dedifferentiation signifies the withdrawal of cells from a specific differentiated state to a stem cell-like undifferentiated state. However, the mechanism of dedifferentiation remains obscure. Here we performed comparative transcriptome analyses during dedifferentiation in mature adipocytes (MAs) to identify the transcriptional signatures of multipotent dedifferentiated fat (DFAT) cells derived from MAs. Using microarray systems, we explored similarly expressed asmore » well as significantly differentially expressed genes in MAs during dedifferentiation. This analysis revealed significant changes in gene expression during this process, including a significant reduction in expression of genes for lipid metabolism concomitantly with a significant increase in expression of genes for cell movement, cell migration, tissue developmental processes, cell growth, cell proliferation, cell morphogenesis, altered cell shape, and cell differentiation. Our observations indicate that the transcriptional signatures of DFAT cells derived from MAs are summarized in terms of a significant decrease in functional phenotype-related genes and a parallel increase in cell proliferation, altered cell morphology, and regulation of the differentiation of related genes. A better understanding of the mechanisms involved in dedifferentiation may enable scientists to control and possibly alter the plasticity of the differentiated state, which may lead to benefits not only in stem cell research but also in regenerative medicine.« less

Proteomics Identification of Potential Candidates Involved in Cell Proliferation for Early Stage of Brain Regeneration in the Adult Zebrafish.

PubMed

Lim, Fei Tieng; Ogawa, Satoshi; Smith, A Ian; Parhar, Ishwar S

2017-02-01

The central nervous system (CNS) of the non-mammalian vertebrates has better neuroregenerative capability as compared with the mammalian CNS. Regeneration of habenula was observed 40 days after damage in zebrafish. During the early stage of regeneration, we found a significant increase of apoptotic cells on day-1 post-damage and of proliferative cells on day-3 post-damage. To identify the molecular factor(s) involved in the early stages of neuroregeneration, differentially expressed proteins during sham, 20- and 40-h post-habenula damage were investigated by proteomic approach by using two-dimensional differential gel electrophoresis (2D-DIGE) coupled with Matrix-Assisted Laser Desorption/Ionization-Time-of-Flight (MALDI-ToF) and tandem mass spectrometry. Protein profiles revealed 17 differentially (>1.5-fold) expressed proteins: 10 upregulated, 4 downregulated, 2 proteins were found to be downregulated at the early stage but upregulated at a later stage, and 1 protein was found to be upregulated at 2 different time points. All proteins identified can be summarized under few molecular processes involved in the early stages of neuroregeneration in zebrafish CNS: apoptosis regulation (Wnt inhibitory factor 1 [WIF1]), neuroprotection (metallothionein), cell proliferation (Spred2, ependymin, Lhx1, and Wnts), differentiation (Spred2, Lhx9, and Wnts), and morphogenesis (cytoplasmic actins and draculin). These protein profiling results suggest that drastic molecular changes occur in the neuroregenerative process during this period, which includes cell proliferation, differentiation, and protection.

Electromagnetic Radiation Disturbed the Photosynthesis of Microcystis aeruginosa at the Proteomics Level.

PubMed

Tang, Chao; Yang, Chuanjun; Yu, Hui; Tian, Shen; Huang, Xiaomei; Wang, Weiyi; Cai, Peng

2018-01-11

Photosynthesis of Microcystis aeruginosa under Electromagnetic Radiation (1.8 GHz, 40 V/m) was studied by using the proteomics. A total of 30 differentially expressed proteins, including 15 up-regulated and 15 down-regulated proteins, were obtained in this study. The differentially expressed proteins were significantly enriched in the photosynthesis pathway, in which the protein expression levels of photosystems II cytochrome b559 α subunit, cytochrome C550, PsbY, and F-type ATP synthase (a, b) decreased. Our results indicated that electromagnetic radiation altered the photosynthesis-related protein expression levels, and aimed at the function of photosynthetic pigments, photosystems II potential activity, photosynthetic electron transport process, and photosynthetic phosphorylation process of M. aeruginosa. Based on the above evidence, that photoreaction system may be deduced as a target of electromagnetic radiation on the photosynthesis in cyanobacteria; the photoreaction system of cyanobacteria is a hypothetical "shared target effector" that responds to light and electromagnetic radiation; moreover, electromagnetic radiation does not act on the functional proteins themselves but their expression processes.

Prx1 and Prx2 cooperatively regulate the morphogenesis of the medial region of the mandibular process

PubMed Central

Balic, Anamaria; Adams, Douglas; Mina, Mina

2009-01-01

Mice lacking both Prx1 and Prx2 display severe abnormalities in the mandible. Our analysis showed that complete loss of Prx gene products leads to growth abnormalities in the mandibular processes evident as early as E10.5 associated with changes in the survival of the mesenchyme in the medial region. Changes in the gene expression in the medial and lateral regions were related to gradual loss of a subpopulation of mesenchyme in the medial region expressing eHand. Our analysis also showed that Prx gene products are required for the initiation and maintenance of chondrogenesis and terminal differentiation of the chondrocytes in the caudal and rostral ends of Meckel’s cartilage. The fusion of the mandibular processes in the Prx1/Prx2 double mutants is caused by accelerated ossification. These observations together show that during mandibular morphogenesis Prx gene products play multiple roles including the cell survival, the region-specific terminal differentiation of Meckelian chondrocytes and osteogenesis. PMID:19777594

Photocatalysis versus photosynthesis: A sensitivity analysis of devices for solar energy conversion and chemical transformations

DOE PAGES

Osterloh, Frank E.

2017-01-18

Here, the chemical literature often does not differentiate between photocatalytic (PC) and photosynthetic (PS) processes (including artificial photosynthesis) even though these reactions differ in their thermodynamics. Photocatalytic processes are thermodynamically downhill (ΔG < 0) and are merely accelerated by the catalyst, whereas photosynthetic processes are thermodynamically unfavorable (ΔG > 0) and require photochemical energy input to occur. Here we apply this differentiation to analyze the basic functions of PC and PS devices and to formulate design criteria for improved performance. As will be shown, the corresponding devices exhibit distinctly different sensitivities to their functional parameters. For example, under conditions ofmore » optimal light absorption, carrier lifetimes, and electrochemical rates, the performance of PCs is limited only by their surface area, while type 1 PS devices are limited by their carrier mobility and mass transport, and type 2 PS devices are limited by electrochemical charge-transfer selectivity. Strategies for the optimization of type 1 and 2 photosynthetic devices and photocatalysts are also discussed.« less

Photocatalysis versus photosynthesis: A sensitivity analysis of devices for solar energy conversion and chemical transformations

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

Osterloh, Frank E.

Here, the chemical literature often does not differentiate between photocatalytic (PC) and photosynthetic (PS) processes (including artificial photosynthesis) even though these reactions differ in their thermodynamics. Photocatalytic processes are thermodynamically downhill (ΔG < 0) and are merely accelerated by the catalyst, whereas photosynthetic processes are thermodynamically unfavorable (ΔG > 0) and require photochemical energy input to occur. Here we apply this differentiation to analyze the basic functions of PC and PS devices and to formulate design criteria for improved performance. As will be shown, the corresponding devices exhibit distinctly different sensitivities to their functional parameters. For example, under conditions ofmore » optimal light absorption, carrier lifetimes, and electrochemical rates, the performance of PCs is limited only by their surface area, while type 1 PS devices are limited by their carrier mobility and mass transport, and type 2 PS devices are limited by electrochemical charge-transfer selectivity. Strategies for the optimization of type 1 and 2 photosynthetic devices and photocatalysts are also discussed.« less

Stimulus sequence context differentially modulates inhibition-related theta and delta band activity in a go/nogo task

PubMed Central

Harper, Jeremy; Malone, Stephen M.; Bachman, Matthew D.; Bernat, Edward M.

2015-01-01

Recent work suggests that dissociable activity in theta and delta frequency bands underlies several common event-related potential (ERP) components, including the nogo N2/P3 complex, which can better index separable functional processes than traditional time-domain measures. Reports have also demonstrated that neural activity can be affected by stimulus sequence context information (i.e., the number and type of preceding stimuli). Stemming from prior work demonstrating that theta and delta index separable processes during response inhibition, the current study assessed sequence context in a Go/Nogo paradigm in which the number of go stimuli preceding each nogo was selectively manipulated. Principal component analysis (PCA) of time-frequency representations revealed differential modulation of evoked theta and delta related to sequence context, where delta increased robustly with additional preceding go stimuli, while theta did not. Findings are consistent with the view that theta indexes simpler initial salience-related processes, while delta indexes more varied and complex processes related to a variety of task parameters. PMID:26751830

Comparative transcriptome analysis reveals differentially expressed genes associated with sex expression in garden asparagus (Asparagus officinalis).

PubMed

Li, Shu-Fen; Zhang, Guo-Jun; Zhang, Xue-Jin; Yuan, Jin-Hong; Deng, Chuan-Liang; Gao, Wu-Jun

2017-08-22

Garden asparagus (Asparagus officinalis) is a highly valuable vegetable crop of commercial and nutritional interest. It is also commonly used to investigate the mechanisms of sex determination and differentiation in plants. However, the sex expression mechanisms in asparagus remain poorly understood. De novo transcriptome sequencing via Illumina paired-end sequencing revealed more than 26 billion bases of high-quality sequence data from male and female asparagus flower buds. A total of 72,626 unigenes with an average length of 979 bp were assembled. In comparative transcriptome analysis, 4876 differentially expressed genes (DEGs) were identified in the possible sex-determining stage of female and male/supermale flower buds. Of these DEGs, 433, including 285 male/supermale-biased and 149 female-biased genes, were annotated as flower related. Of the male/supermale-biased flower-related genes, 102 were probably involved in anther development. In addition, 43 DEGs implicated in hormone response and biosynthesis putatively associated with sex expression and reproduction were discovered. Moreover, 128 transcription factor (TF)-related genes belonging to various families were found to be differentially expressed, and this finding implied the essential roles of TF in sex determination or differentiation in asparagus. Correlation analysis indicated that miRNA-DEG pairs were also implicated in asparagus sexual development. Our study identified a large number of DEGs involved in the sex expression and reproduction of asparagus, including known genes participating in plant reproduction, plant hormone signaling, TF encoding, and genes with unclear functions. We also found that miRNAs might be involved in the sex differentiation process. Our study could provide a valuable basis for further investigations on the regulatory networks of sex determination and differentiation in asparagus and facilitate further genetic and genomic studies on this dioecious species.

Primary Metabolism during Biosynthesis of Secondary Wall Polymers of Protoxylem Vessel Elements1[OPEN

PubMed Central

Morisaki, Keiko; Sawada, Yuji; Sano, Ryosuke; Yamamoto, Atsushi; Kurata, Tetsuya; Suzuki, Shiro; Matsuda, Mami; Hasunuma, Tomohisa; Hirai, Masami Yokota

2016-01-01

Xylem vessels, the water-conducting cells in vascular plants, undergo characteristic secondary wall deposition and programmed cell death. These processes are regulated by the VASCULAR-RELATED NAC-DOMAIN (VND) transcription factors. Here, to identify changes in metabolism that occur during protoxylem vessel element differentiation, we subjected tobacco (Nicotiana tabacum) BY-2 suspension culture cells carrying an inducible VND7 system to liquid chromatography-mass spectrometry-based wide-target metabolome analysis and transcriptome analysis. Time-course data for 128 metabolites showed dynamic changes in metabolites related to amino acid biosynthesis. The concentration of glyceraldehyde 3-phosphate, an important intermediate of the glycolysis pathway, immediately decreased in the initial stages of cell differentiation. As cell differentiation progressed, specific amino acids accumulated, including the shikimate-related amino acids and the translocatable nitrogen-rich amino acid arginine. Transcriptome data indicated that cell differentiation involved the active up-regulation of genes encoding the enzymes catalyzing fructose 6-phosphate biosynthesis from glyceraldehyde 3-phosphate, phosphoenolpyruvate biosynthesis from oxaloacetate, and phenylalanine biosynthesis, which includes shikimate pathway enzymes. Concomitantly, active changes in the amount of fructose 6-phosphate and phosphoenolpyruvate were detected during cell differentiation. Taken together, our results show that protoxylem vessel element differentiation is associated with changes in primary metabolism, which could facilitate the production of polysaccharides and lignin monomers and, thus, promote the formation of the secondary cell wall. Also, these metabolic shifts correlate with the active transcriptional regulation of specific enzyme genes. Therefore, our observations indicate that primary metabolism is actively regulated during protoxylem vessel element differentiation to alter the cell’s metabolic activity for the biosynthesis of secondary wall polymers. PMID:27600813

Magnetic resonance imaging differential diagnosis of brainstem lesions in children

PubMed Central

Quattrocchi, Carlo Cosimo; Errante, Yuri; Rossi Espagnet, Maria Camilla; Galassi, Stefania; Della Sala, Sabino Walter; Bernardi, Bruno; Fariello, Giuseppe; Longo, Daniela

2016-01-01

Differential diagnosis of brainstem lesions, either isolated or in association with cerebellar and supra-tentorial lesions, can be challenging. Knowledge of the structural organization is crucial for the differential diagnosis and establishment of prognosis of pathologies with involvement of the brainstem. Familiarity with the location of the lesions in the brainstem is essential, especially in the pediatric population. Magnetic resonance imaging (MRI) is the most sensitive and specific imaging technique for diagnosing disorders of the posterior fossa and, particularly, the brainstem. High magnetic static field MRI allows detailed visualization of the morphology, signal intensity and metabolic content of the brainstem nuclei, together with visualization of the normal development and myelination. In this pictorial essay we review the brainstem pathology in pediatric patients and consider the MR imaging patterns that may help the radiologist to differentiate among vascular, toxico-metabolic, infective-inflammatory, degenerative and neoplastic processes. Helpful MR tips can guide the differential diagnosis: These include the location and morphology of lesions, the brainstem vascularization territories, gray and white matter distribution and tissue selective vulnerability. PMID:26834941

Derivation of kinetic equations from non-Wiener stochastic differential equations

NASA Astrophysics Data System (ADS)

Basharov, A. M.

2013-12-01

Kinetic differential-difference equations containing terms with fractional derivatives and describing α -stable Levy processes with 0 < α < 1 have been derived in a unified manner in terms of one-dimensional stochastic differential equations controlled merely by the Poisson processes.

Phenotype discovery by gene expression profiling: mapping of biological processes linked to BMP-2-mediated osteoblast differentiation.

PubMed

Balint, Eva; Lapointe, David; Drissi, Hicham; van der Meijden, Caroline; Young, Daniel W; van Wijnen, Andre J; Stein, Janet L; Stein, Gary S; Lian, Jane B

2003-05-15

Understanding physiological control of osteoblast differentiation necessitates characterization of the regulatory signals that initiate the events directing a cell to lineage commitment and establishing competency for bone formation. The bone morphogenetic protein, BMP-2, a member of the TGFbeta superfamily, induces osteoblast differentiation and functions through the Smad signal transduction pathway during in vivo bone formation. However, the molecular targets of BMP-mediated gene transcription during the process of osteoblast differentiation have not been comprehensively identified. In the present study, BMP-2 responsive factors involved in the early stages of commitment and differentiation to the osteoblast phenotype were analyzed by microarray gene expression profiling in samples ranging from 1 to 24 h following BMP-2 dependent differentiation of C2C12 premyoblasts into the osteogenic lineage. A total of 1,800 genes were responsive to BMP-2 and expression was modulated from 3- to 14-fold for less than 100 genes during the time course. Approximately 50% of these 100 genes are either up- or downregulated. Major events associated with phenotypic changes towards the osteogenic lineage were identified from hierarchical and functional clustering analyses. BMP-2 immediately responsive genes (1-4 h), which exhibited either transient or sustained expression, reflect activation and repression of non-osseous BMP-2 developmental systems. This initial response was followed by waves of expression of nuclear proteins and developmental regulatory factors including inhibitors of DNA binding, Runx2, C/EBP, Zn finger binding proteins, forkhead, and numerous homeobox proteins (e.g., CDP/cut, paired, distaless, Hox) which are expressed at characterized stages during osteoblast differentiation. A sequential profile of genes mediating changes in cell morphology, cell growth, and basement membrane formation is observed as a secondary transient early response (2-8 h). Commitment to the osteogenic phenotype is recognized by 8 h, reflected by downregulation of most myogenic-related genes and induction of a spectrum of signaling proteins and enzymes facilitating synthesis and assembly of an extracellular skeletal environment. These genes included collagens Type I and VI and the small leucine rich repeat family of proteoglycans (e.g., decorin, biglycan, osteomodulin, fibromodulin, and osteoadherin/osteoglycin) that reached peak expression at 24 h. With extracellular matrix development, the bone phenotype was further established from 16 to 24 h by induction of genes for cell adhesion and communication and enzymes that organize the bone ECM. Our microarray analysis resulted in the discovery of a class of genes, initially described in relation to differentiation of astrocytes and oligodendrocytes that are functionally coupled to signals for cellular extensions. They include nexin, neuropilin, latexin, neuroglian, neuron specific gene 1, and Ulip; suggesting novel roles for these genes in the bone microenvironment. This global analysis identified a multistage molecular and cellular cascade that supports BMP-2-mediated osteoblast differentiation. Copyright 2003 Wiley-Liss, Inc.

Regulatory mechanism of protein metabolic pathway during the differentiation process of chicken male germ cell.

PubMed

Li, Dong; Zuo, Qisheng; Lian, Chao; Zhang, Lei; Shi, Qingqing; Zhang, Zhentao; Wang, Yingjie; Ahmed, Mahmoud F; Tang, Beibei; Xiao, Tianrong; Zhang, Yani; Li, Bichun

2015-08-01

We explored the regulatory mechanism of protein metabolism during the differentiation process of chicken male germ cells and provide a basis for improving the induction system of embryonic stem cell differentiation to male germ cells in vitro. We sequenced the transcriptome of embryonic stem cells, primordial germ cells, and spermatogonial stem cells with RNA sequencing (RNA-Seq), bioinformatics analysis methods, and detection of the key genes by quantitative reverse transcription PCR (qRT-PCR). Finally, we found 16 amino acid metabolic pathways enriched in the biological metabolism during the differentiation process of embryonic stem cells to primordial germ cells and 15 amino acid metabolic pathways enriched in the differentiation stage of primordial germ cells to spermatogonial stem cells. We found three pathways, arginine-proline metabolic pathway, tyrosine metabolic pathway, and tryptophan metabolic pathway, significantly enriched in the whole differentiation process of embryonic stem cells to spermatogonial stem cells. Moreover, for these three pathways, we screened key genes such as NOS2, ADC, FAH, and IDO. qRT-PCR results showed that the expression trend of these genes were the same to RNA-Seq. Our findings showed that the three pathways and these key genes play an important role in the differentiation process of embryonic stem cells to male germ cells. These results provide basic information for improving the induction system of embryonic stem cell differentiation to male germ cells in vitro.

Cell Expansion During Directed Differentiation of Stem Cells Toward the Hepatic Lineage.

PubMed

Raju, Ravali; Chau, David; Cho, Dong Seong; Park, Yonsil; Verfaillie, Catherine M; Hu, Wei-Shou

2017-02-15

The differentiation of human pluripotent stem cells toward the hepatocyte lineage can potentially provide an unlimited source of functional hepatocytes for transplantation and extracorporeal bioartificial liver applications. It is anticipated that the quantities of cells needed for these applications will be in the order of 10 9 -10 10 cells, because of the size of the liver. An ideal differentiation protocol would be to enable directed differentiation to the hepatocyte lineage with simultaneous cell expansion. We introduced a cell expansion stage after the commitment of human embryonic stem cells to the endodermal lineage, to allow for at least an eightfold increase in cell number, with continuation of cell maturation toward the hepatocyte lineage. The progressive changes in the transcriptome were measured by expression array, and the expression dynamics of certain lineage markers was measured by mass cytometry during the differentiation and expansion process. The findings revealed that while cells were expanding they were also capable of progressing in their differentiation toward the hepatocyte lineage. In addition, our transcriptome, protein and functional studies, including albumin secretion, drug-induced CYP450 expression and urea production, all indicated that the hepatocyte-like cells obtained with or without cell expansion are very similar. This method of simultaneous cell expansion and hepatocyte differentiation should facilitate obtaining large quantities of cells for liver cell applications.

Raman and Autofluorescence Spectrum Dynamics along the HRG-Induced Differentiation Pathway of MCF-7 Cells

PubMed Central

Morita, Shin-ichi; Takanezawa, Sota; Hiroshima, Michio; Mitsui, Toshiyuki; Ozaki, Yukihiro; Sako, Yasushi

2014-01-01

Cellular differentiation proceeds along complicated pathways, even when it is induced by extracellular signaling molecules. One of the major reasons for this complexity is the highly multidimensional internal dynamics of cells, which sometimes causes apparently stochastic responses in individual cells to extracellular stimuli. Therefore, to understand cell differentiation, it is necessary to monitor the internal dynamics of cells at single-cell resolution. Here, we used a Raman and autofluorescence spectrum analysis of single cells to detect dynamic changes in intracellular molecular components. MCF-7 cells are a human cancer-derived cell line that can be induced to differentiate into mammary-gland-like cells with the addition of heregulin (HRG) to the culture medium. We measured the spectra in the cytoplasm of MCF-7 cells during 12 days of HRG stimulation. The Raman scattering spectrum, which was the major component of the signal, changed with time. A multicomponent analysis of the Raman spectrum revealed that the dynamics of the major components of the intracellular molecules, including proteins and lipids, changed cyclically along the differentiation pathway. The background autofluorescence signals of Raman scattering also provided information about the differentiation process. Using the total information from the Raman and autofluorescence spectra, we were able to visualize the pathway of cell differentiation in the multicomponent phase space. PMID:25418290

Novel mechanisms for the vitamin D receptor (VDR) in the skin and in skin cancer.

PubMed

Bikle, Daniel D; Oda, Yuko; Tu, Chia-Ling; Jiang, Yan

2015-04-01

The VDR acting with or without its principal ligand 1,25(OH)2D regulates two central processes in the skin, interfollicular epidermal (IFE) differentiation and hair follicle cycling (HFC). Calcium is an important co-regulator with 1,25(OH)2D at least of epidermal differentiation. Knockout of the calcium sensing receptor (CaSR) in addition to VDR accelerates the development of skin cancer in mice on a low calcium diet. Coactivators such as mediator 1 (aka DRIP205) and steroid receptor coactivator 3 (SRC3) regulate VDR function at different stages of the differentiation process, with Med 1 essential for hair follicle differentiation and early stages of epidermal differentiation and proliferation and SRC3 essential for the latter stages of differentiation including formation of the permeability barrier and innate immunity. The corepressor of VDR, hairless (HR), is essential for hair follicle cycling, although its effect on epidermal differentiation in vivo is minimal. In its regulation of HFC and IFE VDR controls two pathways-wnt/β-catenin and sonic hedgehog (SHH). In the absence of VDR these pathways are overexpressed leading to tumor formation. Whereas, VDR binding to β-catenin may block its activation of TCF/LEF1 sites, β-catenin binding to VDR may enhance its activation of VDREs. 1,25(OH)2D promotes but may not be required for these interactions. Suppression of SHH expression by VDR, on the other hand, requires 1,25(OH)2D. The major point of emphasis is that the role of VDR in the skin involves a number of novel mechanisms, both 1,25(OH)2D dependent and independent, that when disrupted interfere with IFE differentiation and HFC, predisposing to cancer formation. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ordinary differential equations with applications in molecular biology.

PubMed

Ilea, M; Turnea, M; Rotariu, M

2012-01-01

Differential equations are of basic importance in molecular biology mathematics because many biological laws and relations appear mathematically in the form of a differential equation. In this article we presented some applications of mathematical models represented by ordinary differential equations in molecular biology. The vast majority of quantitative models in cell and molecular biology are formulated in terms of ordinary differential equations for the time evolution of concentrations of molecular species. Assuming that the diffusion in the cell is high enough to make the spatial distribution of molecules homogenous, these equations describe systems with many participating molecules of each kind. We propose an original mathematical model with small parameter for biological phospholipid pathway. All the equations system includes small parameter epsilon. The smallness of epsilon is relative to the size of the solution domain. If we reduce the size of the solution region the same small epsilon will result in a different condition number. It is clear that the solution for a smaller region is less difficult. We introduce the mathematical technique known as boundary function method for singular perturbation system. In this system, the small parameter is an asymptotic variable, different from the independent variable. In general, the solutions of such equations exhibit multiscale phenomena. Singularly perturbed problems form a special class of problems containing a small parameter which may tend to zero. Many molecular biology processes can be quantitatively characterized by ordinary differential equations. Mathematical cell biology is a very active and fast growing interdisciplinary area in which mathematical concepts, techniques, and models are applied to a variety of problems in developmental medicine and bioengineering. Among the different modeling approaches, ordinary differential equations (ODE) are particularly important and have led to significant advances. Ordinary differential equations are used to model biological processes on various levels ranging from DNA molecules or biosynthesis phospholipids on the cellular level.

Plasma rich in growth factors (PRGF-Endoret) stimulates proliferation and migration of primary keratocytes and conjunctival fibroblasts and inhibits and reverts TGF-beta1-Induced myodifferentiation.

PubMed

Anitua, Eduardo; Sanchez, Mikel; Merayo-Lloves, Jesus; De la Fuente, Maria; Muruzabal, Francisco; Orive, Gorka

2011-08-01

Plasma rich in growth factors (PRGF-Endoret) technology is an autologous platelet-enriched plasma obtained from patient's own blood, which after activation with calcium chloride allows the release of a pool of biologically active proteins that influence and promote a range of biological processes including cell recruitment, and growth and differentiation. Because ocular surface wound healing is mediated by different growth factors, we decided to explore the potential of PRGF-Endoret technology in stimulating the biological processes related with fibroblast-induced tissue repair. Furthermore, the anti-fibrotic properties of this technology were also studied. Blood from healthy donors was collected, centrifuged and, whole plasma column (WP) and the plasma fraction with the highest platelet concentration (F3) were drawn off, avoiding the buffy coat. Primary human cells including keratocytes and conjunctival fibroblasts were used to perform the "in vitro" investigations. The potential of PRGF-Endoret in promoting wound healing was evaluated by means of a proliferation and migration assays. Fibroblast cells were induced to myofibroblast differentiation after the treatment with 2.5 ng/mL of TGF-β1. The capability of WP and F3 to prevent and inhibit TGF-β1-induced differentiation was evaluated. Results show that this autologous approach significantly enhances proliferation and migration of both keratocytes and conjunctival fibroblasts. In addition, plasma rich in growth factors prevents and inhibits TGF-β1-induced myofibroblast differentiation. No differences were found between WP and F3 plasma fractions. These results suggest that PRGF-Endoret could reduce scarring while stimulating wound healing in ocular surface. F3 or whole plasma column show similar biological effects in keratocytes and conjunctival fibroblast cells.

Transcriptome Profile at Different Physiological Stages Reveals Potential Mode for Curly Fleece in Chinese Tan Sheep

PubMed Central

Liu, Yufang; Xu, Qinqin; Zhang, Ming; Fang, Meiying

2013-01-01

Tan sheep (Ovis aries), a Chinese indigenous breed, has special curly fleece after birth, especially at one month old. However, this unique phenotype disappears gradually with age and the underlying reasons of trait evolvement are still unknown. In this study, skin transcriptome data was used to study this issue. In total 51,215 transcripts including described transcripts and transfrags were identified. Pathway analysis of the top 100 most highly expressed transcripts, which included TCHH and keratin gene family members, such as KRT25, KRT5, KRT71, KRT14 and others, showed pathways known to be relevant to hair/fleece development and function. Six hundred differentially expressed (DE) transcripts were detected at two different physiological ages (one-month-old with curly fleece and 48-month-old without curly fleece) and were categorized into three major functional groups: cellular component, molecular function, and biological process. The top six functional categories included cell, cell part, cellular process, binding, intracellular, metabolic process. The detected differentially expressed genes were particularly involved in signal, signal peptide, disulfide bond, glycoprotein and secreted terms, respectively. Further splicing isoform analysis showed that the metallothionein 3 isoform was up-regulated in Tan lamb skin, indicating that it may be related to the conformation of curly fleece in Chinese Tan lamb. The hair-related important differentially expressed genes (SPINK4, FGF21, ESRα, EphA3, NTNG1 and GPR110) were confirmed by qPCR analysis. We deduced that the differences existed in expressed transcripts, splice isoforms and GO categories between the two different physiological stages, which might constitute the major reasons for explaining the trait evolvement of curly fleece in Chinese Tan sheep. This study provides some clues for elucidating the molecular mechanism of fleece change with age in Chinese Tan sheep, as well as supplying some potential values for understanding human hair disorder and texture changes. PMID:23990983

Hemispheric Asymmetry of Visual Scene Processing in the Human Brain: Evidence from Repetition Priming and Intrinsic Activity

PubMed Central

Kahn, Itamar; Wig, Gagan S.; Schacter, Daniel L.

2012-01-01

Asymmetrical specialization of cognitive processes across the cerebral hemispheres is a hallmark of healthy brain development and an important evolutionary trait underlying higher cognition in humans. While previous research, including studies of priming, divided visual field presentation, and split-brain patients, demonstrates a general pattern of right/left asymmetry of form-specific versus form-abstract visual processing, little is known about brain organization underlying this dissociation. Here, using repetition priming of complex visual scenes and high-resolution functional magnetic resonance imaging (MRI), we demonstrate asymmetrical form specificity of visual processing between the right and left hemispheres within a region known to be critical for processing of visual spatial scenes (parahippocampal place area [PPA]). Next, we use resting-state functional connectivity MRI analyses to demonstrate that this functional asymmetry is associated with differential intrinsic activity correlations of the right versus left PPA with regions critically involved in perceptual versus conceptual processing, respectively. Our results demonstrate that the PPA comprises lateralized subregions across the cerebral hemispheres that are engaged in functionally dissociable yet complementary components of visual scene analysis. Furthermore, this functional asymmetry is associated with differential intrinsic functional connectivity of the PPA with distinct brain areas known to mediate dissociable cognitive processes. PMID:21968568

Hemispheric asymmetry of visual scene processing in the human brain: evidence from repetition priming and intrinsic activity.

PubMed

Stevens, W Dale; Kahn, Itamar; Wig, Gagan S; Schacter, Daniel L

2012-08-01

Asymmetrical specialization of cognitive processes across the cerebral hemispheres is a hallmark of healthy brain development and an important evolutionary trait underlying higher cognition in humans. While previous research, including studies of priming, divided visual field presentation, and split-brain patients, demonstrates a general pattern of right/left asymmetry of form-specific versus form-abstract visual processing, little is known about brain organization underlying this dissociation. Here, using repetition priming of complex visual scenes and high-resolution functional magnetic resonance imaging (MRI), we demonstrate asymmetrical form specificity of visual processing between the right and left hemispheres within a region known to be critical for processing of visual spatial scenes (parahippocampal place area [PPA]). Next, we use resting-state functional connectivity MRI analyses to demonstrate that this functional asymmetry is associated with differential intrinsic activity correlations of the right versus left PPA with regions critically involved in perceptual versus conceptual processing, respectively. Our results demonstrate that the PPA comprises lateralized subregions across the cerebral hemispheres that are engaged in functionally dissociable yet complementary components of visual scene analysis. Furthermore, this functional asymmetry is associated with differential intrinsic functional connectivity of the PPA with distinct brain areas known to mediate dissociable cognitive processes.

Potassium isotope variations in forearc boninite-series volcanics from Chichijima

NASA Astrophysics Data System (ADS)

Parendo, C. A.; Jacobsen, S. B.; Yamashita, K.; Okano, O.

2017-12-01

Variability in the K content of arc lavas is related to fundamental processes. These include (1) the transfer of material from the subducting slab to the mantle wedge, (2) melting occurring within the mantle wedge, and (3) differentiation processes, such as fractional crystallization, which greatly modify the compositions of magma bodies that erupt arc lavas. To explore these processes, samples from Chichijima, an island that is part of the Izu-Bonin forearc, were analyzed for 41K/39K ratios. Analyses were made using an Isoprobe-P MC-ICPMS equipped with a hexapole collision and reaction cell. Precisions obtained were typically about 0.05 ‰ (2SE). We have acquired 41K/39K ratios from eight samples. 41K/39K ratios are reported relative to an estimate of Bulk Silicate Earth. Six of the analyzed samples have 41K/39K ratios that span a range between -0.01 and -0.48 ‰. One sample has a much higher value, +0.44 ‰, and one a much lower value, -1.38 ‰. The samples are variably differentiated, with MgO content ranging approximately from 17 to 1 wt. %. An apparent trend is observed in which the most primitive lavas have 41K/39K ratios near 0.0 ‰ and more evolved lavas have more negative values. A working hypothesis is that 41K/39K ratios vary among these samples because of fractional crystallization. However, multiple other processes need to be considered, including, for some samples, possible post-emplacement alteration. If fractional crystallization is controlling 41K/39K ratios, this requires a precipitating mineral that both incorporates a substantial amount of K and fractionates 41K/39K ratios. Minerals that potentially meet these criteria include feldspars and micas. Effects on 41K/39K ratios may become more pronounced during the later stages of differentiation, when precipitating minerals incorporate more K. Further study will test this hypothesis and explore which minerals may be causing isotopic fractionation. If the fractional crystallization effects can be understood, then it should also be possible to see through these effects and estimate the 41K/39K ratios of the parental magmas.

Longitudinal Course and Correlates of Parents' Differential Treatment of Siblings in Mexican-Origin Families.

PubMed

Padilla, Jenny; McHale, Susan M; Rodríguez De Jesús, Sue A; Updegraff, Kimberly A; Umaña-Taylor, Adriana J

2017-11-02

Parents' differential treatment (PDT) is a common family dynamic that has been linked to youth development and well-being, including adjustment problems and poor sibling relationships. Much less is known, however, about the developmental course of PDT and the conditions under which parents treat their children differently in adolescence and young adulthood. This study examined longitudinal changes in mothers' and fathers' differential warmth and conflict with their two offspring from early adolescence through young adulthood and examined parents' experiences of individual stress (depressive symptoms and role overload) and marital difficulties as time-varying correlates of (changes in) PDT. We also tested crossover effects to determine whether mothers' experiences of individual stress and marital difficulties were linked to fathers' differential treatment, and vice versa. Participants were mothers, fathers, and two siblings from 246 Mexican-origin families who were interviewed in their homes on three occasions over 8 years. Multilevel models revealed that mothers' and fathers' differential conflict with their two children increased until middle adolescence and then declined into young adulthood, but there were no changes over time for parents' differential warmth. In general, both mothers' and fathers' levels of differential treatment were exacerbated by their own experiences of individual stress and marital difficulties and also by the experiences of their spouses. However, in some cases, greater stress than usual was linked to less differential treatment than usual. © 2017 Family Process Institute.

Differential Effects of Motor Efference Copies and Proprioceptive Information on Response Evaluation Processes

PubMed Central

Stock, Ann-Kathrin; Wascher, Edmund; Beste, Christian

2013-01-01

It is well-kown that sensory information influences the way we execute motor responses. However, less is known about if and how sensory and motor information are integrated in the subsequent process of response evaluation. We used a modified Simon Task to investigate how these streams of information are integrated in response evaluation processes, applying an in-depth neurophysiological analysis of event-related potentials (ERPs), time-frequency decomposition and sLORETA. The results show that response evaluation processes are differentially modulated by afferent proprioceptive information and efference copies. While the influence of proprioceptive information is mediated via oscillations in different frequency bands, efference copy based information about the motor execution is specifically mediated via oscillations in the theta frequency band. Stages of visual perception and attention were not modulated by the interaction of proprioception and motor efference copies. Brain areas modulated by the interactive effects of proprioceptive and efference copy based information included the middle frontal gyrus and the supplementary motor area (SMA), suggesting that these areas integrate sensory information for the purpose of response evaluation. The results show how motor response evaluation processes are modulated by information about both the execution and the location of a response. PMID:23658624

Differentiation of mesenchymal stem cells into neuronal cells on fetal bovine acellular dermal matrix as a tissue engineered nerve scaffold

PubMed Central

Feng, Yuping; Wang, Jiao; Ling, Shixin; Li, Zhuo; Li, Mingsheng; Li, Qiongyi; Ma, Zongren; Yu, Sijiu

2014-01-01

The purpose of this study was to assess fetal bovine acellular dermal matrix as a scaffold for supporting the differentiation of bone marrow mesenchymal stem cells into neural cells following induction with neural differentiation medium. We performed long-term, continuous observation of cell morphology, growth, differentiation, and neuronal development using several microscopy techniques in conjunction with immunohistochemistry. We examined specific neuronal proteins and Nissl bodies involved in the differentiation process in order to determine the neuronal differentiation of bone marrow mesenchymal stem cells. The results show that bone marrow mesenchymal stem cells that differentiate on fetal bovine acellular dermal matrix display neuronal morphology with unipolar and bi/multipolar neurite elongations that express neuronal-specific proteins, including βIII tubulin. The bone marrow mesenchymal stem cells grown on fetal bovine acellular dermal matrix and induced for long periods of time with neural differentiation medium differentiated into a multilayered neural network-like structure with long nerve fibers that was composed of several parallel microfibers and neuronal cells, forming a complete neural circuit with dendrite-dendrite to axon-dendrite to dendrite-axon synapses. In addition, growth cones with filopodia were observed using scanning electron microscopy. Paraffin sectioning showed differentiated bone marrow mesenchymal stem cells with the typical features of neuronal phenotype, such as a large, round nucleus and a cytoplasm full of Nissl bodies. The data suggest that the biological scaffold fetal bovine acellular dermal matrix is capable of supporting human bone marrow mesenchymal stem cell differentiation into functional neurons and the subsequent formation of tissue engineered nerve. PMID:25598779

Profiling of differential gene expression in the hypothalamus of broiler-type Taiwan country chickens in response to acute heat stress.

PubMed

Tu, Wei-Lin; Cheng, Chuen-Yu; Wang, Shih-Han; Tang, Pin-Chi; Chen, Chih-Feng; Chen, Hsin-Hsin; Lee, Yen-Pai; Chen, Shuen-Ei; Huang, San-Yuan

2016-02-01

Acute heat stress severely impacts poultry production. The hypothalamus acts as a crucial center to regulate body temperature, detect temperature changes, and modulate the autonomic nervous system and endocrine loop for heat retention and dissipation. The purpose of this study was to investigate global gene expression in the hypothalamus of broiler-type B strain Taiwan country chickens after acute heat stress. Twelve 30-week-old hens were allocated to four groups. Three heat-stressed groups were subjected to acute heat stress at 38 °C for 2 hours without recovery (H2R0), with 2 hours of recovery (H2R2), and with 6 hours of recovery (H2R6). The control hens were maintained at 25 °C. At the end, hypothalamus samples were collected for gene expression analysis. The results showed that 24, 11, and 25 genes were upregulated and 41, 15, and 42 genes were downregulated in H2R0, H2R2, and H2R6 treatments, respectively. The expressions of gonadotropin-releasing hormone 1 (GNRH1), heat shock 27-kDa protein 1 (HSPB1), neuropeptide Y (NPY), and heat shock protein 25 (HSP25) were upregulated at all recovery times after heat exposure. Conversely, the expression of TPH2 was downregulated at all recovery times. A gene ontology analysis showed that most of the differentially expressed genes were involved in biological processes including cellular processes, metabolic processes, localization, multicellular organismal processes, developmental processes, and biological regulation. A functional annotation analysis showed that the differentially expressed genes were related to the gene networks of responses to stress and reproductive functions. These differentially expressed genes might be essential and unique key factors in the heat stress response of the hypothalamus in chickens. Copyright © 2016 Elsevier Inc. All rights reserved.

Honeybees (Apis mellifera) Learn Color Discriminations via Differential Conditioning Independent of Long Wavelength (Green) Photoreceptor Modulation

PubMed Central

Wijesekara Witharanage, Randika; Rosa, Marcello G. P.

2012-01-01

Background Recent studies on colour discrimination suggest that experience is an important factor in how a visual system processes spectral signals. In insects it has been shown that differential conditioning is important for processing fine colour discriminations. However, the visual system of many insects, including the honeybee, has a complex set of neural pathways, in which input from the long wavelength sensitive (‘green’) photoreceptor may be processed either as an independent achromatic signal or as part of a trichromatic opponent-colour system. Thus, a potential confound of colour learning in insects is the possibility that modulation of the ‘green’ photoreceptor could underlie observations. Methodology/Principal Findings We tested honeybee vision using light emitting diodes centered on 414 and 424 nm wavelengths, which limit activation to the short-wavelength-sensitive (‘UV’) and medium-wavelength-sensitive (‘blue’) photoreceptors. The absolute irradiance spectra of stimuli was measured and modelled at both receptor and colour processing levels, and stimuli were then presented to the bees in a Y-maze at a large visual angle (26°), to ensure chromatic processing. Sixteen bees were trained over 50 trials, using either appetitive differential conditioning (N = 8), or aversive-appetitive differential conditioning (N = 8). In both cases the bees slowly learned to discriminate between the target and distractor with significantly better accuracy than would be expected by chance. Control experiments confirmed that changing stimulus intensity in transfers tests does not significantly affect bee performance, and it was possible to replicate previous findings that bees do not learn similar colour stimuli with absolute conditioning. Conclusion Our data indicate that honeybee colour vision can be tuned to relatively small spectral differences, independent of ‘green’ photoreceptor contrast and brightness cues. We thus show that colour vision is at least partly experience dependent, and behavioural plasticity plays an important role in how bees exploit colour information. PMID:23155394

Differential dynamic microscopy of bidisperse colloidal suspensions.

PubMed

Safari, Mohammad S; Poling-Skutvik, Ryan; Vekilov, Peter G; Conrad, Jacinta C

2017-01-01

Research tasks in microgravity include monitoring the dynamics of constituents of varying size and mobility in processes such as aggregation, phase separation, or self-assembly. We use differential dynamic microscopy, a method readily implemented with equipment available on the International Space Station, to simultaneously resolve the dynamics of particles of radius 50 nm and 1 μm in bidisperse aqueous suspensions. Whereas traditional dynamic light scattering fails to detect a signal from the larger particles at low concentrations, differential dynamic microscopy exhibits enhanced sensitivity in these conditions by accessing smaller wavevectors where scattering from the large particles is stronger. Interference patterns due to scattering from the large particles induce non-monotonic decay of the amplitude of the dynamic correlation function with the wavevector. We show that the position of the resulting minimum contains information on the vertical position of the particles. Together with the simple instrumental requirements, the enhanced sensitivity of differential dynamic microscopy makes it an appealing alternative to dynamic light scattering to characterize samples with complex dynamics.

PRMT5 is essential for the maintenance of chondrogenic progenitor cells in the limb bud

PubMed Central

Norrie, Jacqueline L.; Li, Qiang; Co, Swanie; Huang, Bau-Lin; Ding, Ding; Uy, Jann C.; Ji, Zhicheng; Mackem, Susan; Bedford, Mark T.; Galli, Antonella; Ji, Hongkai

2016-01-01

During embryonic development, undifferentiated progenitor cells balance the generation of additional progenitor cells with differentiation. Within the developing limb, cartilage cells differentiate from mesodermal progenitors in an ordered process that results in the specification of the correct number of appropriately sized skeletal elements. The internal pathways by which these cells maintain an undifferentiated state while preserving their capacity to differentiate is unknown. Here, we report that the arginine methyltransferase PRMT5 has a crucial role in maintaining progenitor cells. Mouse embryonic buds lacking PRMT5 have severely truncated bones with wispy digits lacking joints. This novel phenotype is caused by widespread cell death that includes mesodermal progenitor cells that have begun to precociously differentiate into cartilage cells. We propose that PRMT5 maintains progenitor cells through its regulation of Bmp4. Intriguingly, adult and embryonic stem cells also require PRMT5 for maintaining pluripotency, suggesting that similar mechanisms might regulate lineage-restricted progenitor cells during organogenesis. PMID:27827819

PRMT5 is essential for the maintenance of chondrogenic progenitor cells in the limb bud.

PubMed

Norrie, Jacqueline L; Li, Qiang; Co, Swanie; Huang, Bau-Lin; Ding, Ding; Uy, Jann C; Ji, Zhicheng; Mackem, Susan; Bedford, Mark T; Galli, Antonella; Ji, Hongkai; Vokes, Steven A

2016-12-15

During embryonic development, undifferentiated progenitor cells balance the generation of additional progenitor cells with differentiation. Within the developing limb, cartilage cells differentiate from mesodermal progenitors in an ordered process that results in the specification of the correct number of appropriately sized skeletal elements. The internal pathways by which these cells maintain an undifferentiated state while preserving their capacity to differentiate is unknown. Here, we report that the arginine methyltransferase PRMT5 has a crucial role in maintaining progenitor cells. Mouse embryonic buds lacking PRMT5 have severely truncated bones with wispy digits lacking joints. This novel phenotype is caused by widespread cell death that includes mesodermal progenitor cells that have begun to precociously differentiate into cartilage cells. We propose that PRMT5 maintains progenitor cells through its regulation of Bmp4 Intriguingly, adult and embryonic stem cells also require PRMT5 for maintaining pluripotency, suggesting that similar mechanisms might regulate lineage-restricted progenitor cells during organogenesis. © 2016. Published by The Company of Biologists Ltd.

Transcriptional regulation of development in heterocyst-forming cyanobacteria.

PubMed

Flores, Enrique; Picossi, Silvia; Valladares, Ana; Herrero, Antonia

2018-04-30

Filamentous, heterocyst-forming cyanobacteria are among the simplest multicellular systems in Nature. In the absence of combined nitrogen, the filaments consist of vegetative cells that fix CO 2 through oxygenic photosynthesis and micro-oxic heterocysts specialized for the fixation of N 2 in a proportion of about 10 to 1. The development of a heterocyst-containing filament involves differentiation of vegetative cells into heterocysts in a process that requires a distinct gene expression program. Two transcription factors are strictly required, NtcA and HetR. The CRP-family protein NtcA directly activates the expression of multiple genes during heterocyst differentiation - in some cases assisted by coactivators including HetR - and in mature heterocysts, whereas HetR is needed to build high NtcA levels in differentiating heterocysts and directly activates some particular genes. A few other regulators of gene expression participate at specific differentiation steps, and a specific transcription factor, CnfR, activates nif gene expression under the micro-oxic conditions of the heterocyst. Copyright © 2018 Elsevier B.V. All rights reserved.

Vinpocetine Attenuates the Osteoblastic Differentiation of Vascular Smooth Muscle Cells.

PubMed

Ma, Yun-Yun; Sun, Lin; Chen, Xiu-Juan; Wang, Na; Yi, Peng-Fei; Song, Min; Zhang, Bo; Wang, Yu-Zhong; Liang, Qiu-Hua

2016-01-01

Vascular calcification is an active process of osteoblastic differentiation of vascular smooth muscle cells; however, its definite mechanism remains unknown. Vinpocetine, a derivative of the alkaloid vincamine, has been demonstrated to inhibit the high glucose-induced proliferation of vascular smooth muscle cells; however, it remains unknown whether vinpocetine can affect the osteoblastic differentiation of vascular smooth muscle cells. We hereby investigated the effect of vinpocetine on vascular calcification using a beta-glycerophosphate-induced cell model. Our results showed that vinpocetine significantly reduced the osteoblast-like phenotypes of vascular smooth muscle cells including ALP activity, osteocalcin, collagen type I, Runx2 and BMP-2 expression as well as the formation of mineralized nodule. Vinpocetine, binding to translocation protein, induced phosphorylation of extracellular signal-related kinase and Akt and thus inhibited the translocation of nuclear factor-kappa B into the nucleus. Silencing of translocator protein significantly attenuated the inhibitory effect of vinpocetine on osteoblastic differentiation of vascular smooth muscle cells. Taken together, vinpocetine may be a promising candidate for the clinical therapy of vascular calcification.

Suppression subtractive hybridization as a tool to identify anthocyanin metabolism-related genes in apple skin.

PubMed

Ban, Yusuke; Moriguchi, Takaya

2010-01-01

The pigmentation of anthocyanins is one of the important determinants for consumer preference and marketability in horticultural crops such as fruits and flowers. To elucidate the mechanisms underlying the physiological process leading to the pigmentation of anthocyanins, identification of the genes differentially expressed in response to anthocyanin accumulation is a useful strategy. Currently, microarrays have been widely used to isolate differentially expressed genes. However, the use of microarrays is limited by its high cost of special apparatus and materials. Therefore, availability of microarrays is limited and does not come into common use at present. Suppression subtractive hybridization (SSH) is an alternative tool that has been widely used to identify differentially expressed genes due to its easy handling and relatively low cost. This chapter describes the procedures for SSH, including RNA extraction from polysaccharides and polyphenol-rich samples, poly(A)+ RNA purification, evaluation of subtraction efficiency, and differential screening using reverse northern in apple skin.

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.

Fibroblast growth factor receptor signaling is essential for lens fiber cell differentiation.

PubMed

Zhao, Haotian; Yang, Tianyu; Madakashira, Bhavani P; Thiels, Cornelius A; Bechtle, Chad A; Garcia, Claudia M; Zhang, Huiming; Yu, Kai; Ornitz, David M; Beebe, David C; Robinson, Michael L

2008-06-15

The vertebrate lens provides an excellent model to study the mechanisms that regulate terminal differentiation. Although fibroblast growth factors (FGFs) are thought to be important for lens cell differentiation, it is unclear which FGF receptors mediate these processes during different stages of lens development. Deletion of three FGF receptors (Fgfr1-3) early in lens development demonstrated that expression of only a single allele of Fgfr2 or Fgfr3 was sufficient for grossly normal lens development, while mice possessing only a single Fgfr1 allele developed cataracts and microphthalmia. Profound defects were observed in lenses lacking all three Fgfrs. These included lack of fiber cell elongation, abnormal proliferation in prospective lens fiber cells, reduced expression of the cell cycle inhibitors p27(kip1) and p57(kip2), increased apoptosis and aberrant or reduced expression of Prox1, Pax6, c-Maf, E-cadherin and alpha-, beta- and gamma-crystallins. Therefore, while signaling by FGF receptors is essential for lens fiber differentiation, different FGF receptors function redundantly.

Differential diagnosis between dementia and psychiatric disorders: Diagnostic criteria and supplementary exams. Recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology

PubMed Central

Bottino, Cássio M.C.; de Pádua, Analuiza Camozzato; Smid, Jerusa; Areza-Fegyveres, Renata; Novaretti, Tânia; Bahia, Valeria S.

2011-01-01

In 2005, the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology published recommendations for the diagnosis of Alzheimer's disease These recommendations were updated following a review of evidence retrieved from national and international studies held on PUBMED, SCIELO and LILACS medical databases. The main aims of this review article are as follows: 1) to present the evidence found on Brazilian (LILACS, SCIELO) and International (MEDLINE) databases from articles published up to May 2011, on the differential diagnosis of these psychiatric disorders and dementia, with special focus on Dementia due to Alzheimer's and vascular dementia, including a review of supplementary exams which may facilitate the diagnostic process; and 2) to propose recommendations for use by clinicians and researchers involved in diagnosing patients with dementia. Differential diagnosis between dementia and other neuropsychiatric disorders should always include assessments for depression, delirium, and use of psychoactive substances, as well as investigate the use of benzodiazepines, anti-epileptics and pattern of alcohol consumption. PMID:29213755

Differential diagnosis between dementia and psychiatric disorders: Diagnostic criteria and supplementary exams. Recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology.

PubMed

Bottino, Cássio M C; de Pádua, Analuiza Camozzato; Smid, Jerusa; Areza-Fegyveres, Renata; Novaretti, Tânia; Bahia, Valeria S

2011-01-01

In 2005, the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology published recommendations for the diagnosis of Alzheimer's disease These recommendations were updated following a review of evidence retrieved from national and international studies held on PUBMED, SCIELO and LILACS medical databases. The main aims of this review article are as follows: 1) to present the evidence found on Brazilian (LILACS, SCIELO) and International (MEDLINE) databases from articles published up to May 2011, on the differential diagnosis of these psychiatric disorders and dementia, with special focus on Dementia due to Alzheimer's and vascular dementia, including a review of supplementary exams which may facilitate the diagnostic process; and2) to propose recommendations for use by clinicians and researchers involved in diagnosing patients with dementia. Differential diagnosis between dementia and other neuropsychiatric disorders should always include assessments for depression, delirium , and use of psychoactive substances, as well as investigate the use of benzodiazepines, anti-epileptics and pattern of alcohol consumption.

The representation of conceptual knowledge: visual, auditory, and olfactory imagery compared with semantic processing.

PubMed

Palmiero, Massimiliano; Di Matteo, Rosalia; Belardinelli, Marta Olivetti

2014-05-01

Two experiments comparing imaginative processing in different modalities and semantic processing were carried out to investigate the issue of whether conceptual knowledge can be represented in different format. Participants were asked to judge the similarity between visual images, auditory images, and olfactory images in the imaginative block, if two items belonged to the same category in the semantic block. Items were verbally cued in both experiments. The degree of similarity between the imaginative and semantic items was changed across experiments. Experiment 1 showed that the semantic processing was faster than the visual and the auditory imaginative processing, whereas no differentiation was possible between the semantic processing and the olfactory imaginative processing. Experiment 2 revealed that only the visual imaginative processing could be differentiated from the semantic processing in terms of accuracy. These results showed that the visual and auditory imaginative processing can be differentiated from the semantic processing, although both visual and auditory images strongly rely on semantic representations. On the contrary, no differentiation is possible within the olfactory domain. Results are discussed in the frame of the imagery debate.

c-kit expression profile and regulatory factors during spermatogonial stem cell differentiation

PubMed Central

2013-01-01

Background It has been proven that c-kit is crucial for proliferation, migration, survival and maturation of spermatogenic cells. A periodic expression of c-kit is observed from primordial germ cells (PGCs) to spermatogenetic stem cells (SSCs), However, the expression profile of c-kit during the entire spermatogenesis process is still unclear. This study aims to reveal and compare c-kit expression profiles in the SSCs before and after the anticipated differentiation, as well as to examine its relationship with retinoic acid (RA) stimulation. Results We have found that there are more than 4 transcripts of c-kit expressed in the cell lines and in the testes. The transcripts can be divided into short and long categories. The long transcripts include the full-length canonical c-kit transcript and the 3′ end short transcript. Short transcripts include the 3.4 kb short transcript and several truncated transcripts (1.9-3.2 kb). In addition, the 3.4 kb transcript (starting from intron 9 and covering exons 10 ~ 21) is discovered to be specifically expressed in the spermatogonia. The extracellular domain of Kit is obtained in the spermatogonia stage, but the intracellular domain (50 kDa) is constantly expressed in both SSCs and spermatogonia. The c-kit expression profiles in the testis and the spermatogonial stem cell lines vary after RA stimulation. The wave-like changes of the quantitative expression pattern of c-kit (increase initially and decrease afterwards) during the induction process are similar to that of the in vivo male germ cell development process. Conclusions There are dynamic transcription and translation changes of c-kit before and after SSCs’ anticipated differentiation and most importantly, RA is a significant upstream regulatory factor for c-kit expression. PMID:24161026

Dietary Micronutrients Promote Neuronal Differentiation by Modulating the Mitochondrial-Nuclear Dialogue.

PubMed

Xie, Kui; Sheppard, Allan

2018-07-01

The metabolic requirements of differentiated neurons are significantly different from that of neuronal precursor and neural stem cells. While a re-programming of metabolism is tightly coupled to the neuronal differentiation process, whether shifts in mitochondrial mass, glycolysis, and oxidative phosphorylation are required (or merely consequential) in differentiation is not yet certain. In addition to providing more energy, enhanced metabolism facilitates differentiation by supporting increased neurotransmitter signaling and underpinning epigenetic regulation of gene expression. Both epidemiological and animal studies demonstrate that micronutrients (MNs) significantly influence many aspects of neonatal brain development, particularly neural migration and survival, neurite outgrowth, and process maturation. Here we review recent insights into the importance of metabolic reprogramming in neuronal differentiation, before considering evidence that micronutrient signaling may be key to regulating these processes. © 2018 WILEY Periodicals, Inc.

Analysis of the Effects of Five Factors Relevant to In Vitro Chondrogenesis of Human Mesenchymal Stem Cells Using Factorial Design and High Throughput mRNA-Profiling

PubMed Central

Jakobsen, Rune B.; Østrup, Esben; Zhang, Xiaolan; Mikkelsen, Tarjei S.; Brinchmann, Jan E.

2014-01-01

The in vitro process of chondrogenic differentiation of mesenchymal stem cells for tissue engineering has been shown to require three-dimensional culture along with the addition of differentiation factors to the culture medium. In general, this leads to a phenotype lacking some of the cardinal features of native articular chondrocytes and their extracellular matrix. The factors used vary, but regularly include members of the transforming growth factor β superfamily and dexamethasone, sometimes in conjunction with fibroblast growth factor 2 and insulin-like growth factor 1, however the use of soluble factors to induce chondrogenesis has largely been studied on a single factor basis. In the present study we combined a factorial quality-by-design experiment with high-throughput mRNA profiling of a customized chondrogenesis related gene set as a tool to study in vitro chondrogenesis of human bone marrow derived mesenchymal stem cells in alginate. 48 different conditions of transforming growth factor β 1, 2 and 3, bone morphogenetic protein 2, 4 and 6, dexamethasone, insulin-like growth factor 1, fibroblast growth factor 2 and cell seeding density were included in the experiment. The analysis revealed that the best of the tested differentiation cocktails included transforming growth factor β 1 and dexamethasone. Dexamethasone acted in synergy with transforming growth factor β 1 by increasing many chondrogenic markers while directly downregulating expression of the pro-osteogenic gene osteocalcin. However, all factors beneficial to the expression of desirable hyaline cartilage markers also induced undesirable molecules, indicating that perfect chondrogenic differentiation is not achievable with the current differentiation protocols. PMID:24816923

Differentiation-dependent expression of hypothetical proteins in the neuroblastoma cell line N1E-115.

PubMed

Oh, Ji-eun; Karlmark, Karlin Raja; Shin, Jooho; Hengstschläger, Markus; Lubec, Gert

2006-05-15

Several protein cascades, including signaling, cytoskeletal, chaperones, metabolic, and antioxidant proteins, have been shown to be involved in the process of neuronal differentiation (ND) of neuroblastoma cell lines. No systematic approach to detect hitherto unknown and unnamed proteins or structures that have been predicted upon nucleic acid sequences in ND has been published so far. We therefore decided to screen hypothetical protein (HP) expression by protein profiling. Two-dimensional gel electrophoresis with subsequent matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF/TOF) identification was used for expression analysis of undifferentiated and dimethylsulfoxide-induced neuronally differentiated N1E-115 cells. We unambiguously identified six HPs: Q8C520, Q99LF4, Q9CXS1, Q9DAF8, Q91WT0, and Q8C5G2. A prefoldin domain in Q91WT0, a t-SNARE domain in Q9CXS1, and a bromodomain were observed in Q8C5G2. For the three remaining proteins, no putative function using Pfam, BLOCKS, PROSITE, PRINTS, InterPro, Superfamily, CoPS, and ExPASy could be assigned. While two proteins were present in both cell lines, Q9CXS1 was switched off (i.e., undetectably low) in differentiated cells only, and Q9DAF8, Q91WT0, and Q8C5G2 were switched on in differentiated cells exclusively. Herein, using a proteomic approach suitable for screening and identification of HP, we present HP structures that have been only predicted so far based upon nucleic acid sequences. The four differentially regulated HPs may play a putative role in the process of ND. (c) 2006 Wiley-Liss, Inc.

Indian hedgehog signaling promotes chondrocyte differentiation in enchondral ossification in human cervical ossification of the posterior longitudinal ligament.

PubMed

Sugita, Daisuke; Yayama, Takafumi; Uchida, Kenzo; Kokubo, Yasuo; Nakajima, Hideaki; Yamagishi, Atsushi; Takeura, Naoto; Baba, Hisatoshi

2013-10-15

Histological, immunohistochemical, and immunoblot analyses of the expression of Indian hedgehog (Ihh) signaling in human cervical ossification of the posterior longitudinal ligament (OPLL). To examine the hypothesis that Ihh signaling in correlation with Sox9 and parathyroid-related peptide hormone (PTHrP) facilitates chondrocyte differentiation in enchondral ossification process in human cervical OPLL. In enchondral ossification, certain transcriptional factors regulate cell differentiation. OPLL is characterized by overexpression of these factors and disturbance of the normal cell differentiation process. Ihh signaling is essential for enchondral ossification, especially in chondrocyte hypertrophy. Samples of ossified ligaments were harvested from 45 patients who underwent anterior cervical decompressive surgery for symptomatic OPLL, and 6 control samples from patients with cervical spondylotic myelopathy/radiculopathy without OPLL. The harvested sections were stained with hematoxylin-eosin and toluidine blue, examined by transmission electron microscopy, and immunohistochemically stained for Ihh, PTHrP, Sox9, type X, XI collagen, and alkaline phosphatase. Immunoblot analysis was performed in cultured cells derived from the posterior longitudinal ligaments in the vicinity of the ossified plaque and examined for the expression of these factors. The ossification front in OPLL contained chondrocytes at various differentiation stages, including proliferating chondrocytes in fibrocartilaginous area, hypertrophic chondrocytes around the calcification front, and apoptotic chondrocytes near the ossified area. Immunoreactivity for Ihh and Sox9 was evident in proliferating chondrocytes and was strongly positive for PTHrP in hypertrophic chondrocytes. Mesenchymal cells with blood vessel formation were positive for Ihh, PTHrP, and Sox9. Cultured cells from OPLL tissues expressed significantly higher levels of Ihh, PTHrP, and Sox9 than those in non-OPLL cells. Our results indicated that overexpression of Ihh signaling promotes abnormal chondrocyte differentiation in enchondral ossification and enhances bone formation in OPLL.

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

Smirnov, Sergey V.; Harbacheuski, Ryhor; Lewis-Antes, Anita

Mesenchymal stem cells (MSCs) in bone marrow (BM) regulate the differentiation and proliferation of adjacent hematopoietic precursor cells and contribute to the regeneration of mesenchymal tissues, including bone, cartilage, fat and connective tissue. BM is an important site for the pathogenesis of human cytomegalovirus (HCMV) where the virus establishes latency in hematopoietic progenitors and can transmit after reactivation to neighboring cells. Here we demonstrate that BM-MSCs are permissive to productive HCMV infection, and that HCMV alters the function of MSCs: (i) by changing the repertoire of cell surface molecules in BM-MSCs, HCMV modifies the pattern of interaction between BM-MSCs andmore » hematopoietic cells; (ii) HCMV infection of BM-MSCs undergoing adipogenic or osteogenic differentiation impaired the process of differentiation. Our results suggest that by altering BM-MSC biology, HCMV may contribute to the development of various diseases.« less

Simulation and analysis of differential GPS

NASA Astrophysics Data System (ADS)

Denaro, R. P.

NASA is conducting a research program to evaluate differential Global Positioning System (GPS) concepts for civil helicopter navigation. It is pointed out that the civil helicopter community will probably be an early user of GPS because of the unique mission operations in areas where precise navigation aids are not available. However, many of these applications involve accuracy requirements which cannot be satisfied by conventional GPS. Such applications include remote area search and rescue, offshore oil platform approach, remote area precision landing, and other precise navigation operations. Differential GPS provides a promising approach for meeting very demanding accuracy requirements. The considered procedure eliminates some of the common bias errors experienced by conventional GPS. This is done by making use of a second GPS receiver. A simulation process is developed as a tool for analyzing various scenarios of GPS-referenced civil aircraft navigation.

Progressive Recombination Suppression and Differentiation in Recently Evolved Neo-sex Chromosomes

PubMed Central

Natri, Heini M.; Shikano, Takahito; Merilä, Juha

2013-01-01

Recombination suppression leads to the structural and functional differentiation of sex chromosomes and is thus a crucial step in the process of sex chromosome evolution. Despite extensive theoretical work, the exact processes and mechanisms of recombination suppression and differentiation are not well understood. In threespine sticklebacks (Gasterosteus aculeatus), a different sex chromosome system has recently evolved by a fusion between the Y chromosome and an autosome in the Japan Sea lineage, which diverged from the ancestor of other lineages approximately 2 Ma. We investigated the evolutionary dynamics and differentiation processes of sex chromosomes based on comparative analyses of these divergent lineages using 63 microsatellite loci. Both chromosome-wide differentiation patterns and phylogenetic inferences with X and Y alleles indicated that the ancestral sex chromosomes were extensively differentiated before the divergence of these lineages. In contrast, genetic differentiation appeared to have proceeded only in a small region of the neo-sex chromosomes. The recombination maps constructed for the Japan Sea lineage indicated that recombination has been suppressed or reduced over a large region spanning the ancestral and neo-sex chromosomes. Chromosomal regions exhibiting genetic differentiation and suppressed or reduced recombination were detected continuously and sequentially in the neo-sex chromosomes, suggesting that differentiation has gradually spread from the fusion point following the extension of recombination suppression. Our study illustrates an ongoing process of sex chromosome differentiation, providing empirical support for the theoretical model postulating that recombination suppression and differentiation proceed in a gradual manner in the very early stage of sex chromosome evolution. PMID:23436913

The Diagnostic Challenges of Autoimmune Pancreatitis

PubMed Central

Papp, Kata; Angst, Eliane; Seidel, Stefan; Flury-Frei, Renata; Hetzer, Franc Heinrich

2015-01-01

Autoimmune pancreatitis is a rare but important differential diagnosis from pancreatic cancer. This autoimmune disease can mimic pancreatic cancer by its clinical symptoms, including weight loss and jaundice. Furthermore imaging findings may include a mass of the pancreas. Here we present the case of a 67-year-old male patient diagnosed with autoimmune pancreatitis but showing the well-known symptoms of pancreatic cancer. This emphasizes the difficulties of histological findings and the importance of the correct diagnostic process. PMID:25802499

Neural Mechanisms of Attentional Control Differentiate Trait and State Negative Affect

PubMed Central

Crocker, Laura D.; Heller, Wendy; Spielberg, Jeffrey M.; Warren, Stacie L.; Bredemeier, Keith; Sutton, Bradley P.; Banich, Marie T.; Miller, Gregory A.

2012-01-01

The present research examined the hypothesis that cognitive processes are modulated differentially by trait and state negative affect (NA). Brain activation associated with trait and state NA was measured by fMRI during an attentional control task, the emotion-word Stroop. Performance on the task was disrupted only by state NA. Trait NA was associated with reduced activity in several regions, including a prefrontal area that has been shown to be involved in top-down, goal-directed attentional control. In contrast, state NA was associated with increased activity in several regions, including a prefrontal region that has been shown to be involved in stimulus-driven aspects of attentional control. Results suggest that NA has a significant impact on cognition, and that state and trait NA disrupt attentional control in distinct ways. PMID:22934089

The use of open source bioinformatics tools to dissect transcriptomic data.

PubMed

Nitsche, Benjamin M; Ram, Arthur F J; Meyer, Vera

2012-01-01

Microarrays are a valuable technology to study fungal physiology on a transcriptomic level. Various microarray platforms are available comprising both single and two channel arrays. Despite different technologies, preprocessing of microarray data generally includes quality control, background correction, normalization, and summarization of probe level data. Subsequently, depending on the experimental design, diverse statistical analysis can be performed, including the identification of differentially expressed genes and the construction of gene coexpression networks.We describe how Bioconductor, a collection of open source and open development packages for the statistical programming language R, can be used for dissecting microarray data. We provide fundamental details that facilitate the process of getting started with R and Bioconductor. Using two publicly available microarray datasets from Aspergillus niger, we give detailed protocols on how to identify differentially expressed genes and how to construct gene coexpression networks.

Sleeping beauty: awakening urothelium from its slumber.

PubMed

Balsara, Zarine R; Li, Xue

2017-04-01

The bladder urothelium is essentially quiescent but regenerates readily upon injury. The process of urothelial regeneration harkens back to the process of urothelial development whereby urothelial stem/progenitor cells must proliferate and terminally differentiate to establish all three urothelial layers. How the urothelium regulates the level of proliferation and the timing of differentiation to ensure the precise degree of regeneration is of significant interest in the field. Without a carefully-orchestrated process, urothelial regeneration may be inadequate, thereby exposing the host to toxins or pathogens. Alternatively, regeneration may be excessive, thereby setting the stage for tumor development. This review describes our current understanding of urothelial regeneration. The current controversies surrounding the identity and location of urothelial progenitor cells that mediate urothelial regeneration are discussed and evidence for each model is provided. We emphasize the factors that have been shown to be crucial for urothelial regeneration, including local growth factors that stimulate repair, and epithelial-mesenchymal cross talk, which ensures feedback regulation. Also highlighted is the emerging concept of epigenetic regulation of urothelial regeneration, which additionally fine tunes the process through transcriptional regulation of cell cycle genes and growth and differentiation factors. Finally, we emphasize how several of these pathways and/or programs are often dysregulated during malignant transformation, further corroborating their importance in directing normal urothelial regeneration. Together, evidence in the field suggests that any attempt to exploit regenerative programs for the purposes of enhanced urothelial repair or replacement must take into account this delicate balance. Copyright © 2017 the American Physiological Society.

Sleeping beauty: awakening urothelium from its slumber

PubMed Central

Balsara, Zarine R.

2017-01-01

The bladder urothelium is essentially quiescent but regenerates readily upon injury. The process of urothelial regeneration harkens back to the process of urothelial development whereby urothelial stem/progenitor cells must proliferate and terminally differentiate to establish all three urothelial layers. How the urothelium regulates the level of proliferation and the timing of differentiation to ensure the precise degree of regeneration is of significant interest in the field. Without a carefully-orchestrated process, urothelial regeneration may be inadequate, thereby exposing the host to toxins or pathogens. Alternatively, regeneration may be excessive, thereby setting the stage for tumor development. This review describes our current understanding of urothelial regeneration. The current controversies surrounding the identity and location of urothelial progenitor cells that mediate urothelial regeneration are discussed and evidence for each model is provided. We emphasize the factors that have been shown to be crucial for urothelial regeneration, including local growth factors that stimulate repair, and epithelial-mesenchymal cross talk, which ensures feedback regulation. Also highlighted is the emerging concept of epigenetic regulation of urothelial regeneration, which additionally fine tunes the process through transcriptional regulation of cell cycle genes and growth and differentiation factors. Finally, we emphasize how several of these pathways and/or programs are often dysregulated during malignant transformation, further corroborating their importance in directing normal urothelial regeneration. Together, evidence in the field suggests that any attempt to exploit regenerative programs for the purposes of enhanced urothelial repair or replacement must take into account this delicate balance. PMID:28122714

Vesta Evolution from Surface Mineralogy: Mafic and Ultramafic Mineral Distribution

NASA Technical Reports Server (NTRS)

DeSanctis, M. C.; Ammannito, E.; Palomba, E.; Longobardo, A.; Mittlefehldt, D. W.; McSween, H. Y; Marchi, S.; Capria, M. T.; Capaccioni, F.; Frigeri, A.;

Double ionization of helium by ion impact: second Born order treatment at the fully differential level

NASA Astrophysics Data System (ADS)

López, S. D.; Otranto, S.; Garibotti, C. R.

2015-01-01

In this work, a theoretical study of the double ionization of He by ion impact at the fully differential level is presented. Emphasis is made in the role played by the projectile in the double emission process depending on its charge and the amount of momentum transferred to the target. A Born-CDW model including a second-order term in the projectile charge is introduced and evaluated within an on-shell treatment. We find that emission geometries for which the second-order term dominates lead to asymmetric structures around the momentum transfer direction, a typical characteristic of higher order transitions.

Differential expression profiling of miRNAs between Marek’s disease resistant and susceptible chickens

USDA-ARS?s Scientific Manuscript database

Mounting evidence indicates microRNAs (miRNAs) play important roles in various biological processes including all aspects of cancer biology. The aim of this study was to profile and to assess the differences of miRNAs between the treatment groups of two lines of White Leghorns with or without viral ...

The Nature and Correlates of Sibling Influence in Two-Parent African American Families

ERIC Educational Resources Information Center

Whiteman, Shawn D.; Becerra Bernard, Julia M.; McHale, Susan M.

2010-01-01

Guided by research and theory on sibling similarities and differences, this study explored the nature and correlates of 2 processes of sibling influence--social learning and sibling differentiation--during adolescence. Participants included 2 adolescent-age siblings (M = 16.29 years for older siblings and M = 12.59 years for younger siblings,…

Field guide to old ponderosa pines in the Colorado Front Range

Treesearch

Laurie Stroh Huckaby; Merrill R. Kaufmann; Paula J. Fornwalt; Jason M. Stoker; Chuck Dennis

2003-01-01

We describe the distinguishing physical characteristics of old ponderosa pine trees in the Front Range of Colorado and the ecological processes that tend to preserve them. Photographs illustrate identifying features of old ponderosa pines and show how to differentiate them from mature and young trees. The publication includes a photographic gallery of old ponderosa...

Neural Plasticity: Single Neuron Models for Discrimination and Generalization and an Experimental Ensemble Approach.

DTIC Science & Technology

1983-06-01

Commuents Regarding the Antagonistic Mechanisms Approach .0...... .................................... 67 C. Cognitive Applications...similarities between stimuli, and differentiation* a separation process. An analogous dichotomy in cognitive theory has been extensively studied by Tversky...tasks including perception. cognition , and action. Not all neurons are identical, there exist several anatomically defined categories of these cells

An Empirical Investigation of Occupational Choice and Human Capital Accumulation at Mid-Life

ERIC Educational Resources Information Center

Xue, Yu

2010-01-01

Individual variation in labor supply can arise from more than just a choice among discrete occupation groups, especially given the joint process of wage determination and time allocation. Other factors can include differential preferences for earnings, the time length of work and other related occupational attributes. Using data from the Wisconsin…

Zebrafish numb and numblike are involved in primitive erythrocyte differentiation.

PubMed

Bresciani, Erica; Confalonieri, Stefano; Cermenati, Solei; Cimbro, Simona; Foglia, Efrem; Beltrame, Monica; Di Fiore, Pier Paolo; Cotelli, Franco

2010-12-13

Notch signaling is an evolutionarily conserved regulatory circuitry implicated in cell fate determination in various developmental processes including hematopoietic stem cell self-renewal and differentiation of blood lineages. Known endogenous inhibitors of Notch activity are Numb-Nb and Numblike-Nbl, which play partially redundant functions in specifying and maintaining neuronal differentiation. Nb and Nbl are expressed in most tissues including embryonic and adult hematopoietic tissues in mice and humans, suggesting possible roles for these proteins in hematopoiesis. We employed zebrafish to investigate the possible functional role of Numb and Numblike during hematopoiesis, as this system allows a detailed analysis even in embryos with severe defects that would be lethal in other organisms. Here we describe that nb/nbl knockdown results in severe reduction or absence of embryonic erythrocytes in zebrafish. Interestingly, nb/nbl knocked-down embryos present severe downregulation of the erythroid transcription factor gata1. This results in erythroblasts which fail to mature and undergo apoptosis. Our results indicate that Notch activity is increased in embryos injected with nb/nbl morpholino, and we show that inhibition of Notch activation can partially rescue the hematopoietic phenotype. Our results provide the first in vivo evidence of an involvement of Numb and Numblike in zebrafish erythroid differentiation during primitive hematopoiesis. Furthermore, we found that, at least in part, the nb/nbl morphant phenotype is due to enhanced Notch activation within hematopoietic districts, which in turn results in primitive erythroid differentiation defects.

Characterization of Mediterranean hail-bearing storms using an operational polarimetric X-band radar

NASA Astrophysics Data System (ADS)

Vulpiani, G.; Baldini, L.; Roberto, N.

2015-07-01

This work documents the fruitul use of X-band radar observations for the monitoring of severe storms in an operational framework. More specifically, a couple of severe hail-bearing Mediterranean storms occurred in 2013 in southern Italy, flooding two important cities of Sicily, are described in terms of their polarimetric radar signatures and retrieved rainfall fields. It is used the X-band dual-polarization radar operating inside the Catania airport (Sicily, Italy), managed by the Italian Department of Civil Protection. A suitable processing is applied to X-band radar measurements. The crucial procedural step relies on the differential phase processing based on an iterative approach that uses a very short-length (1 km) moving window allowing to properly catch the observed high radial gradients of the differential phase. The parameterization of the attenuation correction algorithm, which use the reconstructed differential phase shift, is derived from electromagnetic simulations based on 3 years of DSD observations collected in Rome (Italy). A Fuzzy Logic hydrometeor classification algorithm was also adopted to support the analysis of the storm characteristics. The precipitation fields amount were reconstructed using a combined polarimetric rainfall algorithm based on reflectivity and specific differential phase. The first considered storm was observed on the 21 February, when a winter convective system, originated in the Tyrrhenian sea, hit only marginally the central-eastern coastline of Sicily causing the flash-flood of Catania. Due to the optimal radar location (the system is located at just few kilometers from the city center), it was possible to well retrieve the storm characteristics, including the amount of rainfall field at ground. Extemporaneous signal extinction, caused by close-range hail core causing significant differential phase shift in very short range path, is documented. The second storm, occurred on 21 August 2013, is a summer mesoscale convective system originated by the temperature gradient between sea and land surface, lasted a few hours and eventually flooded the city of Siracusa. The undergoing physical process, including the storm dynamics, is inferred by analysing the vertical sections of the polarimetric radar measurements. The high registered precipitation amount was fairly well reconstructed even though with a trend to underestimation at increasing distances. Several episodes of signal extinction clearly manifested during the mature stage of the observed supercell.

Characterization of Mediterranean hail-bearing storms using an operational polarimetric X-band radar

NASA Astrophysics Data System (ADS)

Vulpiani, G.; Baldini, L.; Roberto, N.

2015-11-01

This work documents the effective use of X-band radar observations for monitoring severe storms in an operational framework. Two severe hail-bearing Mediterranean storms that occurred in 2013 in southern Italy, flooding two important Sicilian cities, are described in terms of their polarimetric radar signatures and retrieved rainfall fields. The X-band dual-polarization radar operating inside the Catania airport (Sicily, Italy), managed by the Italian Department of Civil Protection, is considered here. A suitable processing is applied to X-band radar measurements. The crucial procedural step relies on the differential phase processing, being preparatory for attenuation correction and rainfall estimation. It is based on an iterative approach that uses a very short-length (1 km) moving window, allowing proper capture of the observed high radial gradients of the differential phase. The parameterization of the attenuation correction algorithm, which uses the reconstructed differential phase shift, is derived from electromagnetic simulations based on 3 years of drop size distribution (DSD) observations collected in Rome (Italy). A fuzzy logic hydrometeor classification algorithm was also adopted to support the analysis of the storm characteristics. The precipitation field amounts were reconstructed using a combined polarimetric rainfall algorithm based on reflectivity and specific differential phase. The first storm was observed on 21 February when a winter convective system that originated in the Tyrrhenian Sea, marginally hit the central-eastern coastline of Sicily, causing a flash flood in Catania. Due to an optimal location (the system is located a few kilometers from the city center), it was possible to retrieve the storm characteristics fairly well, including the amount of rainfall field at the ground. Extemporaneous signal extinction, caused by close-range hail core causing significant differential phase shift in a very short-range path, is documented. The second storm, on 21 August 2013, was a summer mesoscale convective system that originated from a Mediterranean low pressure system lasting a few hours that eventually flooded the city of Syracuse. The undergoing physical process, including the storm dynamics, is inferred by analyzing the vertical sections of the polarimetric radar measurements. The high registered amount of precipitation was fairly well reconstructed, although with a trend toward underestimation at increasing distances. Several episodes of signal extinction were clearly manifested during the mature stage of the observed supercells.

GeneMesh: a web-based microarray analysis tool for relating differentially expressed genes to MeSH terms.

PubMed

Jani, Saurin D; Argraves, Gary L; Barth, Jeremy L; Argraves, W Scott

2010-04-01

An important objective of DNA microarray-based gene expression experimentation is determining inter-relationships that exist between differentially expressed genes and biological processes, molecular functions, cellular components, signaling pathways, physiologic processes and diseases. Here we describe GeneMesh, a web-based program that facilitates analysis of DNA microarray gene expression data. GeneMesh relates genes in a query set to categories available in the Medical Subject Headings (MeSH) hierarchical index. The interface enables hypothesis driven relational analysis to a specific MeSH subcategory (e.g., Cardiovascular System, Genetic Processes, Immune System Diseases etc.) or unbiased relational analysis to broader MeSH categories (e.g., Anatomy, Biological Sciences, Disease etc.). Genes found associated with a given MeSH category are dynamically linked to facilitate tabular and graphical depiction of Entrez Gene information, Gene Ontology information, KEGG metabolic pathway diagrams and intermolecular interaction information. Expression intensity values of groups of genes that cluster in relation to a given MeSH category, gene ontology or pathway can be displayed as heat maps of Z score-normalized values. GeneMesh operates on gene expression data derived from a number of commercial microarray platforms including Affymetrix, Agilent and Illumina. GeneMesh is a versatile web-based tool for testing and developing new hypotheses through relating genes in a query set (e.g., differentially expressed genes from a DNA microarray experiment) to descriptors making up the hierarchical structure of the National Library of Medicine controlled vocabulary thesaurus, MeSH. The system further enhances the discovery process by providing links between sets of genes associated with a given MeSH category to a rich set of html linked tabular and graphic information including Entrez Gene summaries, gene ontologies, intermolecular interactions, overlays of genes onto KEGG pathway diagrams and heatmaps of expression intensity values. GeneMesh is freely available online at http://proteogenomics.musc.edu/genemesh/.

Composing Models of Geographic Physical Processes

NASA Astrophysics Data System (ADS)

Hofer, Barbara; Frank, Andrew U.

Processes are central for geographic information science; yet geographic information systems (GIS) lack capabilities to represent process related information. A prerequisite to including processes in GIS software is a general method to describe geographic processes independently of application disciplines. This paper presents such a method, namely a process description language. The vocabulary of the process description language is derived formally from mathematical models. Physical processes in geography can be described in two equivalent languages: partial differential equations or partial difference equations, where the latter can be shown graphically and used as a method for application specialists to enter their process models. The vocabulary of the process description language comprises components for describing the general behavior of prototypical geographic physical processes. These process components can be composed by basic models of geographic physical processes, which is shown by means of an example.

The PaPsr1 and PaWhi2 genes are members of the regulatory network that connect stationary phase to mycelium differentiation and reproduction in Podospora anserina.

PubMed

Timpano, Hélène; Chan Ho Tong, Laetitia; Gautier, Valérie; Lalucque, Hervé; Silar, Philippe

2016-09-01

In filamentous fungi, entrance into stationary phase is complex as it is accompanied by several differentiation and developmental processes, including the synthesis of pigments, aerial hyphae, anastomoses and sporophores. The regulatory networks that control these processes are still incompletely known. The analysis of the "Impaired in the development of Crippled Growth (IDC)" mutants of the model filamentous ascomycete Podospora anserina has already yielded important information regarding the pathway regulating entrance into stationary phase. Here, the genes affected in two additional IDC mutants are identified as orthologues of the Saccharomyces cerevisiae WHI2 and PSR1 genes, known to regulate stationary phase in this yeast, arguing for a conserved role of these proteins throughout the evolution of ascomycetes. Copyright © 2016 Elsevier Inc. All rights reserved.

Potential in vivo roles of nucleic acid triple-helices

PubMed Central

Buske, Fabian A

2011-01-01

The ability of double-stranded DNA to form a triple-helical structure by hydrogen bonding with a third strand is well established, but the biological functions of these structures remain largely unknown. There is considerable albeit circumstantial evidence for the existence of nucleic triplexes in vivo and their potential participation in a variety of biological processes including chromatin organization, DNA repair, transcriptional regulation and RNA processing has been investigated in a number of studies to date. There is also a range of possible mechanisms to regulate triplex formation through differential expression of triplex-forming RNAs, alteration of chromatin accessibility, sequence unwinding and nucleotide modifications. With the advent of next generation sequencing technology combined with targeted approaches to isolate triplexes, it is now possible to survey triplex formation with respect to their genomic context, abundance and dynamical changes during differentiation and development, which may open up new vistas in understanding genome biology and gene regulation. PMID:21525785

Ikaros gene expression and leukemia.

PubMed

Tonnelle, Cécile; Calmels, Boris; Maroc, Christine; Gabert, Jean; Chabannon, Christian

2002-01-01

The Ikaros (Ik) protein, or LyF1, was initially described as a protein binding to regulatory sequences of a number of genes expressed in murine lymphoid cells. Ikaros is a critical regulator of normal hematopoietic stem cell differentiation, as evidenced by dramatic defects in the lymphoid compartments, in homozygous animals with gene inactivation. Because differential splicing produces multiple isoforms with potentially different functions, Ikaros provides a unique model to study how post-transcriptional mechanisms may be involved in neoplastic processes. Indeed, several groups including ours have underlined evidences that expression of different Ikaros isoforms vary among different types of leukemias. The predominance of short isoforms in certain subsets is intriguing. Here, additional observations reinforced the hypothesis that Ikaros expression may be deregulated in human leukemias. Whether this is a cause or a consequence of the leukemic process remains speculative. Other human diseases however, provide examples of abnormal post-transcriptional regulations that have been further characterized.

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.

Role of Integrin in Mechanical Loading of Osteoblasts

NASA Technical Reports Server (NTRS)

Globus, Ruth; Demsky, Caroline

2000-01-01

Mechanical forces generated by gravity, weightbearing, and muscle contraction play a key role in the genesis and maintenance of skeletal structure. The molecular mechanisms that mediate changes in osteoblast activity in response to altered patterns of skeletal loading are not known, and a better understanding of these processes may be essential for developing effective treatment strategies to prevent disuse osteoporosis. We have elucidated specific integrin/ECM (extracellular matrix) interactions that are required for osteoblast differentiation and survival and have developed a useful loading system to further explore the molecular basis of mechano-sensitivity of osteoblasts. The long term goal of our collaborative research is to understand how the ECM and cell adhesion proteins and integrins interaction to mediate the response of osteoblasts and their progenitors to mechanical loading. We suggest that integrin/ECM interactions are crucial for basic cellular processes, including differentiation and survival, as well as to participate in detecting and mediating cellular responses to mechanical stimuli.

Death penalty for keratinocytes: apoptosis versus cornification.

PubMed

Lippens, S; Denecker, G; Ovaere, P; Vandenabeele, P; Declercq, W

2005-11-01

Homeostasis implies a balance between cell growth and cell death. This balance is essential for the development and maintenance of multicellular organisms. Homeostasis is controlled by several mechanisms including apoptosis, a process by which cells condemned to death are completely eliminated. However, in some cases, total destruction and removal of dead cells is not desirable, as when they fulfil a specific function such as formation of the skin barrier provided by corneocytes, also known as terminally differentiated keratinocytes. In this case, programmed cell death results in accumulation of functional cell corpses. Previously, this process has been associated with apoptotic cell death. In this overview, we discuss differences and similarities in the molecular regulation of epidermal programmed cell death and apoptosis. We conclude that despite earlier confusion, apoptosis and cornification occur through distinct molecular pathways, and that possibly antiapoptotic mechanisms are implicated in the terminal differentiation of keratinocytes.

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

Modeling formalisms in Systems Biology

PubMed Central

2011-01-01

Systems Biology has taken advantage of computational tools and high-throughput experimental data to model several biological processes. These include signaling, gene regulatory, and metabolic networks. However, most of these models are specific to each kind of network. Their interconnection demands a whole-cell modeling framework for a complete understanding of cellular systems. We describe the features required by an integrated framework for modeling, analyzing and simulating biological processes, and review several modeling formalisms that have been used in Systems Biology including Boolean networks, Bayesian networks, Petri nets, process algebras, constraint-based models, differential equations, rule-based models, interacting state machines, cellular automata, and agent-based models. We compare the features provided by different formalisms, and discuss recent approaches in the integration of these formalisms, as well as possible directions for the future. PMID:22141422

System and process for upgrading hydrocarbons

DOEpatents

Bingham, Dennis N.; Klingler, Kerry M.; Smith, Joseph D.; Turner, Terry D.; Wilding, Bruce M.

2015-08-25

In one embodiment, a system for upgrading a hydrocarbon material may include a black wax upgrade subsystem and a molten salt gasification (MSG) subsystem. The black wax upgrade subsystem and the MSG subsystem may be located within a common pressure boundary, such as within a pressure vessel. Gaseous materials produced by the MSG subsystem may be used in the process carried out within the black wax upgrade subsystem. For example, hydrogen may pass through a gaseous transfer interface to interact with black wax feed material to hydrogenate such material during a cracking process. In one embodiment, the gaseous transfer interface may include one or more openings in a tube or conduit which is carrying the black wax material. A pressure differential may control the flow of hydrogen within the tube or conduit. Related methods are also disclosed.

Neuropeptides and epitheliopeptides: structural and functional diversity in an ancestral metazoan Hydra.

PubMed

Takahashi, Toshio

2013-06-01

Peptides are known to play important developmental and physiological roles in signaling. The rich diversity of peptides, with functions as diverse as intercellular communication, neurotransmission and signaling that spatially and temporally controls axis formation and cell differentiation, hints at the wealth of information passed between interacting cells. Little is known about peptides that control developmental processes such as cell differentiation and pattern formation in metazoans. The cnidarian Hydra is one of the most basic metazoans and is a key model system for study of the peptides involved in these processes. We developed a novel peptidomic approach for the isolation and identification of functional peptide signaling molecules from Hydra (the Hydra Peptide Project). Over the course of this project, a wide variety of novel neuropeptides were identified. Most of these peptides act directly on muscle cells and their functions include induction of contraction and relaxation. Some peptides are involved in cell differentiation and morphogenesis. Moreover, epitheliopeptides that are produced by epithelial cells were originally identified in Hydra. Some of these epitheliopeptides exhibit morphogen-like activities, whereas others are involved in regulating neuron differentiation, possibly through neuron-epithelial cell interactions. We also describe below our high-throughput reverse-phase nano-flow LCMALDI- TOF-MS/MS approach, which has proved a powerful tool for the discovery of novel peptide signaling molecules in Hydra.

Epidermal cornification is preceded by the expression of a keratinocyte-specific set of pyroptosis-related genes.

PubMed

Lachner, Julia; Mlitz, Veronika; Tschachler, Erwin; Eckhart, Leopold

2017-12-12

The homeostasis of the epidermis depends on keratinocyte differentiation and cornification, a mode of programmed cell death that does not elicit inflammation. Here, we report that cornification is associated with the expression of specific genes that control multiple steps of pyroptosis, another form of cell death that involves the processing and release of interleukin-1 family (IL1F) cytokines. Expression levels of pro-inflammatory IL1A and IL1B and of the pyroptotic pore-forming gasdermin (GSDM) D were downregulated during terminal differentiation of human keratinocytes in vitro. By contrast, negative regulators of IL-1 processing, including NLR family pyrin domain containing 10 (NLRP10) and pyrin domain-containing 1 (PYDC1), the anti-inflammatory IL1F members IL-37 (IL1F7) and IL-38 (IL1F10), and GSDMA, were strongly induced in differentiated keratinocytes. In human tissues, these keratinocyte differentiation-associated genes are expressed in the skin at higher levels than in any other organ, and mammalian species, that have lost the epidermal cornification program during evolution, i.e. whales and dolphins, lack homologs of these genes. Together, our results suggest that human epidermal cornification is accompanied by a tight control of pyroptosis and warrant further studies of potential defects in the balance between cornification and pyroptosis in skin pathologies.

Proliferation and osteogenic differentiation of rat BMSCs on a novel Ti/SiC metal matrix nanocomposite modified by friction stir processing

PubMed Central

Zhu, Chenyuan; Lv, Yuting; Qian, Chao; Qian, Haixin; Jiao, Ting; Wang, Liqiang; Zhang, Fuqiang

2016-01-01

The aims of this study were to fabricate a novel titanium/silicon carbide (Ti/SiC) metal matrix nanocomposite (MMNC) by friction stir processing (FSP) and to investigate its microstructure and mechanical properties. In addition, the adhesion, proliferation and osteogenic differentiation of rat bone marrow stromal cells (BMSCs) on the nanocomposite surface were investigated. The MMNC microstructure was observed by both scanning and transmission electron microscopy. Mechanical properties were characterized by nanoindentation and Vickers hardness testing. Integrin β1 immunofluorescence, cell adhesion, and MTT assays were used to evaluate the effects of the nanocomposite on cell adhesion and proliferation. Osteogenic and angiogenic differentiation were evaluated by alkaline phosphatase (ALP) staining, ALP activity, PCR and osteocalcin immunofluorescence. The observed microstructures and mechanical properties clearly indicated that FSP is a very effective technique for modifying Ti/SiC MMNC to contain uniformly distributed nanoparticles. In the interiors of recrystallized grains, characteristics including twins, fine recrystallized grains, and dislocations formed concurrently. Adhesion, proliferation, and osteogenic and angiogenic differentiation of rat BMSCs were all enhanced on the novel Ti/SiC MMNC surface. In conclusion, nanocomposites modified using FSP technology not only have superior mechanical properties under stress-bearing conditions but also provide improved surface and physicochemical properties for cell attachment and osseointegration. PMID:27958394

Comprehensive analysis of a microRNA expression profile in pediatric medulloblastoma.

PubMed

Dai, Junqiang; Li, Qiao; Bing, Zhitong; Zhang, Yinian; Niu, Liang; Yin, Hang; Yuan, Guoqiang; Pan, Yawen

2017-06-01

Medulloblastoma is the most common malignant brain tumor of the central nervous system among children. Medulloblastoma is an embryonal tumor, of which little is known about the pathogenesis. Several efforts have been made to understand the molecular aspects of its tumorigenic pathways; however, these are poorly understood. microRNA (miRNA), a type of non‑coding short RNA, has been proven to be associated with a number of physiological processes and pathological processes of serious diseases, including brain tumors. Differentially expressed miRNAs serve an important role in numerous types of malignancy. The present study aims to define a differentially expressed set of miRNAs in medulloblastoma tumor tissue, compared with normal samples, to improve the understanding of the tumorigenesis. It was identified that 22 miRNAs were upregulated and 26 miRNAs were downregulated in the tumor tissue compared with the normal group. However, when the medulloblastoma tissue was compared with normal cerebellum tissue, 9 miRNAs were identified to be up or downregulated in the tumor samples. The differentially expressed miRNAs in the tumor tissue were identified in order to clarify the networks and pathways of tumorigenesis using Ingenuity Pathway Analysis. Subsequently, key regulatory genes associated with the development of medulloblastoma were identified, including tumor protein p53, insulin like growth factor 1 receptor, argonaute 2, mitogen‑activated protein kinases 1 and 3, sirtuin 1 and Y box binding protein 1.

The functional genetic link of NLGN4X knockdown and neurodevelopment in neural stem cells

PubMed Central

Shi, Lingling; Chang, Xiao; Zhang, Peilin; Coba, Marcelo P.; Lu, Wange; Wang, Kai

2013-01-01

Genetic mutations in NLGN4X (neuroligin 4), including point mutations and copy number variants (CNVs), have been associated with susceptibility to autism spectrum disorders (ASDs). However, it is unclear how mutations in NLGN4X result in neurodevelopmental defects. Here, we used neural stem cells (NSCs) as in vitro models to explore the impacts of NLGN4X knockdown on neurodevelopment. Using two shRNAmir-based vectors targeting NLGN4X and one control shRNAmir vector, we modulated NLGN4X expression and differentiated these NSCs into mature neurons. We monitored the neurodevelopmental process at Weeks 0, 0.5, 1, 2, 4 and 6, based on morphological analysis and whole-genome gene expression profiling. At the cellular level, in NSCs with NLGN4X knockdown, we observed increasingly delayed neuronal development and compromised neurite formation, starting from Week 2 through Week 6 post differentiation. At the molecular level, we identified multiple pathways, such as neurogenesis, neuron differentiation and muscle development, which are increasingly disturbed in cells with NLGN4X knockdown. Notably, several postsynaptic genes, including DLG4, NLGN1 and NLGN3, also have decreased expression. Based on in vitro models, NLGN4X knockdown directly impacts neurodevelopmental process during the formation of neurons and their connections. Our functional genomics study highlights the utility of NSCs models in understanding the functional roles of CNVs in affecting neurodevelopment and conferring susceptibility to neurodevelopmental diseases. PMID:23710042

The functional genetic link of NLGN4X knockdown and neurodevelopment in neural stem cells.

PubMed

Shi, Lingling; Chang, Xiao; Zhang, Peilin; Coba, Marcelo P; Lu, Wange; Wang, Kai

2013-09-15

Genetic mutations in NLGN4X (neuroligin 4), including point mutations and copy number variants (CNVs), have been associated with susceptibility to autism spectrum disorders (ASDs). However, it is unclear how mutations in NLGN4X result in neurodevelopmental defects. Here, we used neural stem cells (NSCs) as in vitro models to explore the impacts of NLGN4X knockdown on neurodevelopment. Using two shRNAmir-based vectors targeting NLGN4X and one control shRNAmir vector, we modulated NLGN4X expression and differentiated these NSCs into mature neurons. We monitored the neurodevelopmental process at Weeks 0, 0.5, 1, 2, 4 and 6, based on morphological analysis and whole-genome gene expression profiling. At the cellular level, in NSCs with NLGN4X knockdown, we observed increasingly delayed neuronal development and compromised neurite formation, starting from Week 2 through Week 6 post differentiation. At the molecular level, we identified multiple pathways, such as neurogenesis, neuron differentiation and muscle development, which are increasingly disturbed in cells with NLGN4X knockdown. Notably, several postsynaptic genes, including DLG4, NLGN1 and NLGN3, also have decreased expression. Based on in vitro models, NLGN4X knockdown directly impacts neurodevelopmental process during the formation of neurons and their connections. Our functional genomics study highlights the utility of NSCs models in understanding the functional roles of CNVs in affecting neurodevelopment and conferring susceptibility to neurodevelopmental diseases.

Nuclear phosphoproteome analysis of 3T3-L1 preadipocyte differentiation reveals system-wide phosphorylation of transcriptional regulators.

PubMed

Rabiee, Atefeh; Schwämmle, Veit; Sidoli, Simone; Dai, Jie; Rogowska-Wrzesinska, Adelina; Mandrup, Susanne; Jensen, Ole N

2017-03-01

Adipocytes (fat cells) are important endocrine and metabolic cells critical for systemic insulin sensitivity. Both adipose excess and insufficiency are associated with adverse metabolic function. Adipogenesis is the process whereby preadipocyte precursor cells differentiate into lipid-laden mature adipocytes. This process is driven by a network of transcriptional regulators (TRs). We hypothesized that protein PTMs, in particular phosphorylation, play a major role in activating and propagating signals within TR networks upon induction of adipogenesis by extracellular stimulus. We applied MS-based quantitative proteomics and phosphoproteomics to monitor the alteration of nuclear proteins during the early stages (4 h) of preadipocyte differentiation. We identified a total of 4072 proteins including 2434 phosphorylated proteins, a majority of which were assigned as regulators of gene expression. Our results demonstrate that adipogenic stimuli increase the nuclear abundance and/or the phosphorylation levels of proteins involved in gene expression, cell organization, and oxidation-reduction pathways. Furthermore, proteins acting as negative modulators involved in negative regulation of gene expression, insulin stimulated glucose uptake, and cytoskeletal organization showed a decrease in their nuclear abundance and/or phosphorylation levels during the first 4 h of adipogenesis. Among 288 identified TRs, 49 were regulated within 4 h of adipogenic stimulation including several known and many novel potential adipogenic regulators. We created a kinase-substrate database for 3T3-L1 preadipocytes by investigating the relationship between protein kinases and protein phosphorylation sites identified in our dataset. A majority of the putative protein kinases belong to the cyclin-dependent kinase family and the mitogen-activated protein kinase family including P38 and c-Jun N-terminal kinases, suggesting that these kinases act as orchestrators of early adipogenesis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comprehensive processing of high-throughput small RNA sequencing data including quality checking, normalization, and differential expression analysis using the UEA sRNA Workbench

PubMed Central

Beckers, Matthew; Mohorianu, Irina; Stocks, Matthew; Applegate, Christopher; Dalmay, Tamas; Moulton, Vincent

2017-01-01

Recently, high-throughput sequencing (HTS) has revealed compelling details about the small RNA (sRNA) population in eukaryotes. These 20 to 25 nt noncoding RNAs can influence gene expression by acting as guides for the sequence-specific regulatory mechanism known as RNA silencing. The increase in sequencing depth and number of samples per project enables a better understanding of the role sRNAs play by facilitating the study of expression patterns. However, the intricacy of the biological hypotheses coupled with a lack of appropriate tools often leads to inadequate mining of the available data and thus, an incomplete description of the biological mechanisms involved. To enable a comprehensive study of differential expression in sRNA data sets, we present a new interactive pipeline that guides researchers through the various stages of data preprocessing and analysis. This includes various tools, some of which we specifically developed for sRNA analysis, for quality checking and normalization of sRNA samples as well as tools for the detection of differentially expressed sRNAs and identification of the resulting expression patterns. The pipeline is available within the UEA sRNA Workbench, a user-friendly software package for the processing of sRNA data sets. We demonstrate the use of the pipeline on a H. sapiens data set; additional examples on a B. terrestris data set and on an A. thaliana data set are described in the Supplemental Information. A comparison with existing approaches is also included, which exemplifies some of the issues that need to be addressed for sRNA analysis and how the new pipeline may be used to do this. PMID:28289155

Platelet lysate induces chondrogenic differentiation of umbilical cord-derived mesenchymal stem cells.

PubMed

Hassan, Ghmkin; Bahjat, Mohammad; Kasem, Issam; Soukkarieh, Chadi; Aljamali, Majd

2018-01-01

Articular cartilage has a poor capacity for self-repair, and thus still presents a major challenge in orthopedics. Mesenchymal stem cells (MSCs) are multipotent stem cells with the potential to differentiate into chondrocytes in the presence of transforming growth factor beta (TGF-β). Platelet lysate (PL) contains a relatively large number of growth factors, including TGF-β, and has been shown to ameliorate cartilage repair. Here, we investigated the ability of PL to direct chondrogenic differentiation of MSCs along with other standard differentiation components in a pellet culture system. We isolated and expanded MSCs from human umbilical cords using a PL-supplemented medium and characterized the cells based on immunophenotype and potential for differentiation to adipocytes and osteocytes. We further cultured MSCs as pellets in a chondrogenic-differentiation medium supplemented with PL. After 21 days, the pellets were processed for histological analysis and stained with alician blue and acridine orange. The expression of SOX9 was investigated using RT-PCR. MSCs maintained their stemness characteristics in the PL-supplemented medium. However, the distribution of cells in the pellets cultured in the PL-supplemented chondrogenic differentiation medium had a greater similarity to cartilage tissue-derived chondrocytes than to the negative control. The intense alician blue staining indicated an increased production of mucopolysaccharides in the differentiated pellets, which also showed elevated expression of SOX9 . Our data suggest that MSCs could be differentiated to chondrocytes in the presence of PL and absence of exogenous TGF-β. Further research needs to be conducted to understand the exact role and potential of PL in chondrogenic differentiation and chondrocyte regeneration.

Antioxidants Maintain E-Cadherin Levels to Limit Drosophila Prohemocyte Differentiation

PubMed Central

Gao, Hongjuan; Wu, Xiaorong; Simon, LaTonya; Fossett, Nancy

2014-01-01

Mitochondrial reactive oxygen species (ROS) regulate a variety of biological processes by networking with signal transduction pathways to maintain homeostasis and support adaptation to stress. In this capacity, ROS have been shown to promote the differentiation of progenitor cells, including mammalian embryonic and hematopoietic stem cells and Drosophila hematopoietic progenitors (prohemocytes). However, many questions remain about how ROS alter the regulatory machinery to promote progenitor differentiation. Here, we provide evidence for the hypothesis that ROS reduce E-cadherin levels to promote Drosophila prohemocyte differentiation. Specifically, we show that knockdown of the antioxidants, Superoxide dismutatase 2 and Catalase reduce E-cadherin protein levels prior to the loss of Odd-skipped-expressing prohemocytes. Additionally, over-expression of E-cadherin limits prohemocyte differentiation resulting from paraquat-induced oxidative stress. Furthermore, two established targets of ROS, Enhancer of Polycomb and FOS, control the level of E-cadherin protein expression. Finally, we show that knockdown of either Superoxide dismutatase 2 or Catalase leads to an increase in the E-cadherin repressor, Serpent. As a result, antioxidants and targets of ROS can control E-cadherin protein levels, and over-expression of E-cadherin can ameliorate the prohemocyte response to oxidative stress. Collectively, these data strongly suggest that ROS promote differentiation by reducing E-cadherin levels. In mammalian systems, ROS promote embryonic stem cell differentiation, whereas E-cadherin blocks differentiation. However, it is not known if elevated ROS reduce E-cadherin to promote embryonic stem cell differentiation. Thus, our findings may have identified an important mechanism by which ROS promote stem/progenitor cell differentiation. PMID:25226030

Phytohormonal Networks Promote Differentiation of Fiber Initials on Pre-Anthesis Cotton Ovules Grown In Vitro and In Planta

PubMed Central

Kim, Hee Jin; Hinchliffe, Doug J.; Triplett, Barbara A.; Chen, Z. Jeffrey; Stelly, David M.; Yeater, Kathleen M.; Moon, Hong S.; Gilbert, Matthew K.; Thyssen, Gregory N.; Turley, Rickie B.; Fang, David D.

2015-01-01

The number of cotton (Gossypium sp.) ovule epidermal cells differentiating into fiber initials is an important factor affecting cotton yield and fiber quality. Despite extensive efforts in determining the molecular mechanisms regulating fiber initial differentiation, only a few genes responsible for fiber initial differentiation have been discovered. To identify putative genes directly involved in the fiber initiation process, we used a cotton ovule culture technique that controls the timing of fiber initial differentiation by exogenous phytohormone application in combination with comparative expression analyses between wild type and three fiberless mutants. The addition of exogenous auxin and gibberellins to pre-anthesis wild type ovules that did not have visible fiber initials increased the expression of genes affecting auxin, ethylene, ABA and jasmonic acid signaling pathways within 1 h after treatment. Most transcripts expressed differentially by the phytohormone treatment in vitro were also differentially expressed in the ovules of wild type and fiberless mutants that were grown in planta. In addition to MYB25-like, a gene that was previously shown to be associated with the differentiation of fiber initials, several other differentially expressed genes, including auxin/indole-3-acetic acid (AUX/IAA) involved in auxin signaling, ACC oxidase involved in ethylene biosynthesis, and abscisic acid (ABA) 8'-hydroxylase an enzyme that controls the rate of ABA catabolism, were co-regulated in the pre-anthesis ovules of both wild type and fiberless mutants. These results support the hypothesis that phytohormonal signaling networks regulate the temporal expression of genes responsible for differentiation of cotton fiber initials in vitro and in planta. PMID:25927364

MicroRNA regulation of endothelial homeostasis and commitment-implications for vascular regeneration strategies using stem cell therapies.

PubMed

Scott, Elizabeth; Loya, Komal; Mountford, Joanne; Milligan, Graeme; Baker, Andrew H

2013-09-01

Human embryonic (hESC) and induced pluripotent (hiPSC) stem cells have broad therapeutic potential in the treatment of a range of diseases, including those of the vascular system. Both hESCs and hiPSCs have the capacity for indefinite self-renewal, in addition to their ability to differentiate into any adult cell type. These cells could provide a potentially unlimited source of cells for transplantation and, therefore, provide novel treatments, e.g. in the production of endothelial cells for vascular regeneration. MicroRNAs are short, noncoding RNAs that act posttranscriptionally to control gene expression and thereby exert influence over a wide range of cellular processes, including maintenance of pluripotency and differentiation. Expression patterns of these small RNAs are tissue specific, and changes in microRNA levels have often been associated with disease states in humans, including vascular pathologies. Here, we review the roles of microRNAs in endothelial cell function and vascular disease, as well as their role in the differentiation of pluripotent stem cells to the vascular endothelial lineage. Furthermore, we discuss the therapeutic potential of stem cells and how knowledge and manipulation of microRNAs in stem cells may enhance their capacity for vascular regeneration. © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Transcriptional profiling of murine osteoblast differentiation based on RNA-seq expression analyses.

PubMed

Khayal, Layal Abo; Grünhagen, Johannes; Provazník, Ivo; Mundlos, Stefan; Kornak, Uwe; Robinson, Peter N; Ott, Claus-Eric

2018-04-11

Osteoblastic differentiation is a multistep process characterized by osteogenic induction of mesenchymal stem cells, which then differentiate into proliferative pre-osteoblasts that produce copious amounts of extracellular matrix, followed by stiffening of the extracellular matrix, and matrix mineralization by hydroxylapatite deposition. Although these processes have been well characterized biologically, a detailed transcriptional analysis of murine primary calvaria osteoblast differentiation based on RNA sequencing (RNA-seq) analyses has not previously been reported. Here, we used RNA-seq to obtain expression values of 29,148 genes at four time points as murine primary calvaria osteoblasts differentiate in vitro until onset of mineralization was clearly detectable by microscopic inspection. Expression of marker genes confirmed osteogenic differentiation. We explored differential expression of 1386 protein-coding genes using unsupervised clustering and GO analyses. 100 differentially expressed lncRNAs were investigated by co-expression with protein-coding genes that are localized within the same topologically associated domain. Additionally, we monitored expression of 237 genes that are silent or active at distinct time points and compared differential exon usage. Our data represent an in-depth profiling of murine primary calvaria osteoblast differentiation by RNA-seq and contribute to our understanding of genetic regulation of this key process in osteoblast biology. Copyright © 2018 Elsevier Inc. All rights reserved.

Differentiation and the Twice-Exceptional Student

ERIC Educational Resources Information Center

Franklin-Rohr, Cheryl

2012-01-01

Tier 1, the first level of instruction in the RtI (Response to Intervention) framework, is designed to meet the needs of 80% of students within the regular classroom. The only way to accomplish this goal is to use differentiation. Differentiation is not a singular process; it is rather a complicated process of adapting instructional strategies so…

The Local Brewery: A Project for Use in Differential Equations Courses

ERIC Educational Resources Information Center

Starling, James K.; Povich, Timothy J.; Findlay, Michael

2016-01-01

We describe a modeling project designed for an ordinary differential equations (ODEs) course using first-order and systems of first-order differential equations to model the fermentation process in beer. The project aims to expose the students to the modeling process by creating and solving a mathematical model and effectively communicating their…

GPU computing with Kaczmarz’s and other iterative algorithms for linear systems

PubMed Central

Elble, Joseph M.; Sahinidis, Nikolaos V.; Vouzis, Panagiotis

2009-01-01

The graphics processing unit (GPU) is used to solve large linear systems derived from partial differential equations. The differential equations studied are strongly convection-dominated, of various sizes, and common to many fields, including computational fluid dynamics, heat transfer, and structural mechanics. The paper presents comparisons between GPU and CPU implementations of several well-known iterative methods, including Kaczmarz’s, Cimmino’s, component averaging, conjugate gradient normal residual (CGNR), symmetric successive overrelaxation-preconditioned conjugate gradient, and conjugate-gradient-accelerated component-averaged row projections (CARP-CG). Computations are preformed with dense as well as general banded systems. The results demonstrate that our GPU implementation outperforms CPU implementations of these algorithms, as well as previously studied parallel implementations on Linux clusters and shared memory systems. While the CGNR method had begun to fall out of favor for solving such problems, for the problems studied in this paper, the CGNR method implemented on the GPU performed better than the other methods, including a cluster implementation of the CARP-CG method. PMID:20526446

Resolving the Tevatron Top Quark Forward-Backward Asymmetry Puzzle: Fully Differential Next-to-Next-to-Leading-Order Calculation.

PubMed

Czakon, Michal; Fiedler, Paul; Mitov, Alexander

2015-07-31

We determine the dominant missing standard model (SM) contribution to the top quark pair forward-backward asymmetry at the Tevatron. Contrary to past expectations, we find a large, around 27%, shift relative to the well-known value of the inclusive asymmetry in next-to-leading order QCD. Combining all known standard model corrections, we find that A(FB)(SM)=0.095±0.007. This value is in agreement with the latest DØ measurement [V. M. Abazov et al. (D0 Collaboration), Phys. Rev. D 90, 072011 (2014)] A(FB)(D∅)=0.106±0.03 and about 1.5σ below that of CDF [T. Aaltonen et al. (CDF Collaboration), Phys. Rev. D 87, 092002 (2013)] A(FB)(CDF)=0.164±0.047. Our result is derived from a fully differential calculation of the next-to-next-to leading order (NNLO) QCD corrections to inclusive top pair production at hadron colliders and includes-without any approximation-all partonic channels contributing to this process. This is the first complete fully differential calculation in NNLO QCD of a two-to-two scattering process with all colored partons.

Three-dimensional slice cultures from murine fetal gut for investigations of the enteric nervous system.

PubMed

Metzger, Marco; Bareiss, Petra M; Nikolov, Ivan; Skutella, Thomas; Just, Lothar

2007-01-01

Three-dimensional intestinal cultures offer new possibilities for the examination of growth potential, analysis of time specific gene expression, and spatial cellular arrangement of enteric nervous system in an organotypical environment. We present an easy to produce in vitro model of the enteric nervous system for analysis and manipulation of cellular differentiation processes. Slice cultures of murine fetal colon were cultured on membrane inserts for up to 2 weeks without loss of autonomous contractility. After slice preparation, cultured tissue reorganized within the first days in vitro. Afterward, the culture possessed more than 35 cell layers, including high prismatic epithelial cells, smooth muscle cells, glial cells, and neurons analyzed by immunohistochemistry. The contraction frequency of intestinal slice culture could be modulated by the neurotransmitter serotonin and the sodium channel blocker tetrodotoxin. Coculture experiments with cultured neurospheres isolated from enhanced green fluorescent protein (eGFP) transgenic mice demonstrated that differentiating eGFP-positive neurons were integrated into the intestinal tissue culture. This slice culture model of enteric nervous system proved to be useful for studying cell-cell interactions, cellular signaling, and cell differentiation processes in a three-dimensional cell arrangement.

Identification of differentially expressed lncRNAs involved in transient regeneration of the neonatal C57BL/6J mouse heart by next-generation high-throughput RNA sequencing.

PubMed

Chen, Yu-Mei; Li, Hua; Fan, Yi; Zhang, Qi-Jun; Li, Xing; Wu, Li-Jie; Chen, Zi-Jie; Zhu, Chun; Qian, Ling-Mei

2017-04-25

Previous studies have shown that mammalian cardiac tissue has a regenerative capacity. Remarkably, neonatal mice can regenerate their cardiac tissue for up to 6 days after birth, but this capacity is lost by day 7. In this study, we aimed to explore the expression pattern of long noncoding RNA (lncRNA) during this period and examine the mechanisms underlying this process. We found that 685 lncRNAs and 1833 mRNAs were differentially expressed at P1 and P7 by the next-generation high-throughput RNA sequencing. The coding genes associated with differentially expressed lncRNAs were mainly involved in metabolic processes and cell proliferation, and also were potentially associated with several key regeneration signalling pathways, including PI3K-Akt, MAPK, Hippo and Wnt. In addition, we identified some correlated targets of highly-dysregulated lncRNAs such as Igfbp3, Trnp1, Itgb6, and Pim3 by the coding-noncoding gene co-expression network. These data may offer a reference resource for further investigation about the mechanisms by which lncRNAs regulate cardiac regeneration.

p63 regulates glutaminase 2 expression

PubMed Central

Giacobbe, Arianna; Bongiorno-Borbone, Lucilla; Bernassola, Francesca; Terrinoni, Alessandro; Markert, Elke Katrin; Levine, Arnold J.; Feng, Zhaohui; Agostini, Massimilano; Zolla, Lello; Agrò, Alessandro Finazzi; Notterman, Daniel A.; Melino, Gerry; Peschiaroli, Angelo

2013-01-01

The transcription factor p63 is critical for many biological processes, including development and maintenance of epidermal tissues and tumorigenesis. Here, we report that the TAp63 isoforms regulate cell metabolism through the induction of the mitochondrial glutaminase 2 (GLS2) gene both in primary cells and tumor cell lines. By ChIP analysis and luciferase assay, we confirmed that TAp63 binds directly to the p53/p63 consensus DNA binding sequence within the GLS2 promoter region. Given the critical role of p63 in epidermal differentiation, we have investigated the regulation of GLS2 expression during this process. GLS2 and TAp63 expression increases during the in vitro differentiation of primary human keratinocytes, and depletion of GLS2 inhibits skin differentiation both at molecular and cellular levels. We found that GLS2 and TAp63 expression are concomitantly induced in cancer cells exposed to oxidative stresses. siRNA-mediated depletion of GLS2 sensitizes cells to ROS-induced apoptosis, suggesting that the TAp63/GLS2 axis can be functionally important as a cellular antioxidant pathway in the absence of p53. Accordingly, we found that GLS2 is upregulated in colon adenocarcinoma. Altogether, our findings demonstrate that GLS2 is a bona fide TAp63 target gene, and that the TAp63-dependent regulation of GLS2 is important for both physiological and pathological processes. PMID:23574722

SRSF2 mutations drive oncogenesis by activating a global program of aberrant alternative splicing in hematopoietic cells.

PubMed

Liang, Yang; Tebaldi, Toma; Rejeski, Kai; Joshi, Poorval; Stefani, Giovanni; Taylor, Ashley; Song, Yuanbin; Vasic, Radovan; Maziarz, Jamie; Balasubramanian, Kunthavai; Ardasheva, Anastasia; Ding, Alicia; Quattrone, Alessandro; Halene, Stephanie

2018-06-01

Recurrent mutations in the splicing factor SRSF2 are associated with poor clinical outcomes in myelodysplastic syndromes (MDS). Their high frequency suggests these mutations drive oncogenesis, yet the molecular explanation for this process is unclear. SRSF2 mutations could directly affect pre-mRNA splicing of a vital gene product; alternatively, a whole network of gene products could be affected. Here we determine how SRSF2 mutations globally affect RNA binding and splicing in vivo using HITS-CLIP. Remarkably, the majority of differential binding events do not translate into alternative splicing of exons with SRSF2 P95H binding sites. Alternative splice alterations appear to be dominated by indirect effects. Importantly, SRSF2 P95H targets are enriched in RNA processing and splicing genes, including several members of the hnRNP and SR families of proteins, suggesting a "splicing-cascade" phenotype wherein mutation of a single splicing factor leads to widespread modifications in multiple RNA processing and splicing proteins. We show that splice alteration of HNRNPA2B1, a splicing factor differentially bound and spliced by SRSF2 P95H , impairs hematopoietic differentiation in vivo. Our data suggests a model whereby the recurrent mutations in splicing factors set off a cascade of gene regulatory events that together affect hematopoiesis and drive cancer.

The RNA helicase DDX17 controls the transcriptional activity of REST and the expression of proneural microRNAs in neuronal differentiation.

PubMed

Lambert, Marie-Pierre; Terrone, Sophie; Giraud, Guillaume; Benoit-Pilven, Clara; Cluet, David; Combaret, Valérie; Mortreux, Franck; Auboeuf, Didier; Bourgeois, Cyril F

2018-06-21

The Repressor Element 1-silencing transcription factor (REST) represses a number of neuronal genes in non-neuronal cells or in undifferentiated neural progenitors. Here, we report that the DEAD box RNA helicase DDX17 controls important REST-related processes that are critical during the early phases of neuronal differentiation. First, DDX17 associates with REST, promotes its binding to the promoter of a subset of REST-targeted genes and co-regulates REST transcriptional repression activity. During neuronal differentiation, we observed a downregulation of DDX17 along with that of the REST complex that contributes to the activation of neuronal genes. Second, DDX17 and its paralog DDX5 regulate the expression of several proneural microRNAs that are known to target the REST complex during neurogenesis, including miR-26a/b that are also direct regulators of DDX17 expression. In this context, we propose a new mechanism by which RNA helicases can control the biogenesis of intronic miRNAs. We show that the processing of the miR-26a2 precursor is dependent on RNA helicases, owing to an intronic regulatory region that negatively impacts on both miRNA processing and splicing of its host intron. Our work places DDX17 in the heart of a pathway involving REST and miRNAs that allows neuronal gene repression.

Microtubule actin crosslinking factor 1 promotes osteoblast differentiation by promoting β-catenin/TCF1/Runx2 signaling axis.

PubMed

Hu, Lifang; Su, Peihong; Yin, Chong; Zhang, Yan; Li, Runzhi; Yan, Kun; Chen, Zhihao; Li, Dijie; Zhang, Ge; Wang, Liping; Miao, Zhiping; Qian, Airong; Xian, Cory J

2018-02-01

Osteoblast differentiation is a multistep process delicately regulated by many factors, including cytoskeletal dynamics and signaling pathways. Microtubule actin crosslinking factor 1 (MACF1), a key cytoskeletal linker, has been shown to play key roles in signal transduction and in diverse cellular processes; however, its role in regulating osteoblast differentiation is still needed to be elucidated. To further uncover the functions and mechanisms of action of MACF1 in osteoblast differentiation, we examined effects of MACF1 knockdown (MACF1-KD) in MC3T3-E1 osteoblastic cells on their osteoblast differentiation and associated molecular mechanisms. The results showed that knockdown of MACF1 significantly suppressed mineralization of MC3T3-E1 cells, down-regulated the expression of key osteogenic genes alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2) and type I collagen α1 (Col Iα1). Knockdown of MACF1 dramatically reduced the nuclear translocation of β-catenin, decreased the transcriptional activation of T cell factor 1 (TCF1), and down-regulated the expression of TCF1, lymphoid enhancer-binding factor 1 (LEF1), and Runx2, a target gene of β-catenin/TCF1. In addition, MACF1-KD increased the active level of glycogen synthase kinase-3β (GSK-3β), which is a key regulator for β-catenin signal transduction. Moreover, the reduction of nuclear β-catenin amount and decreased expression of TCF1 and Runx2 were significantly reversed in MACF1-KD cells when treated with lithium chloride, an agonist for β-catenin by inhibiting GSK-3β activity. Taken together, these findings suggest that knockdown of MACF1 in osteoblastic cells inhibits osteoblast differentiation through suppressing the β-catenin/TCF1-Runx2 axis. Thus, a novel role of MACF1 in and a new mechanistic insight of osteoblast differentiation are uncovered. © 2017 Wiley Periodicals, Inc.

Betaine supplement enhances skeletal muscle differentiation in murine myoblasts via IGF-1 signaling activation

PubMed Central

2013-01-01

Background Betaine (BET) is a component of many foods, including spinach and wheat. It is an essential osmolyte and a source of methyl groups. Recent studies have hypothesized that BET might play a role in athletic performance. However, BET effects on skeletal muscle differentiation and hypertrophy are still poorly understood. Methods We examined BET action on neo myotubes maturation and on differentiation process, using C2C12 murine myoblastic cells. We used RT2-PCR array, Western blot and immunofluorescence analysis to study the BET effects on morphological features of C2C12 and on signaling pathways involved in muscle differentiation and hypertrophy. Results We performed a dose–response study, establishing that 10 mM BET was the dose able to stimulate morphological changes and hypertrophic process in neo myotubes. RT2-PCR array methodology was used to identify the expression profile of genes encoding proteins involved in IGF-1 pathway. A dose of 10 mM BET was found to promote IGF-1 receptor (IGF-1 R) expression. Western blot and immunofluorescence analysis, performed in neo myotubes, pointed out that 10 mM BET improved IGF-1 signaling, synthesis of Myosin Heavy Chain (MyHC) and neo myotubes length. In addition, we investigated BET role on myoblasts proliferation and differentiation. During proliferation, BET did not modify C2C12 proliferative rate, but promoted myogenic induction, enhancing MyoD protein content and cellular elongation. During differentiation, BET caused an increase of muscle-specific markers and IGF-1 R protein levels. Conclusions Our findings provide the first evidence that BET could promote muscle fibers differentiation and increase myotubes size by IGF-1 pathway activation, suggesting that BET might represent a possible new drug/integrator strategy, not only in sport performance but also in clinical conditions characterized by muscle function impairment. PMID:23870626

IDH1R132H in Neural Stem Cells: Differentiation Impaired by Increased Apoptosis

PubMed Central

Rosiak, Kamila; Smolarz, Maciej; Stec, Wojciech J.; Peciak, Joanna; Grzela, Dawid; Winiecka-Klimek, Marta; Stoczynska-Fidelus, Ewelina; Krynska, Barbara; Piaskowski, Sylwester; Rieske, Piotr

2016-01-01

Background The high frequency of mutations in the isocitrate dehydrogenase 1 (IDH1) gene in diffuse gliomas indicates its importance in the process of gliomagenesis. These mutations result in loss of the normal function and acquisition of the neomorphic activity converting α-ketoglutarate to 2-hydroxyglutarate. This potential oncometabolite may induce the epigenetic changes, resulting in the deregulated expression of numerous genes, including those related to the differentiation process or cell survivability. Methods Neural stem cells were derived from human induced pluripotent stem cells following embryoid body formation. Neural stem cells transduced with mutant IDH1R132H, empty vector, non-transduced and overexpressing IDH1WT controls were differentiated into astrocytes and neurons in culture. The neuronal and astrocytic differentiation was determined by morphology and expression of lineage specific markers (MAP2, Synapsin I and GFAP) as determined by real-time PCR and immunocytochemical staining. Apoptosis was evaluated by real-time observation of Caspase-3 activation and measurement of PARP cleavage by Western Blot. Results Compared with control groups, cells expressing IDH1R132H retained an undifferentiated state and lacked morphological changes following stimulated differentiation. The significant inhibitory effect of IDH1R132H on neuronal and astrocytic differentiation was confirmed by immunocytochemical staining for markers of neural stem cells. Additionally, real-time PCR indicated suppressed expression of lineage markers. High percentage of apoptotic cells was detected within IDH1R132H-positive neural stem cells population and their derivatives, if compared to normal neural stem cells and their derivatives. The analysis of PARP and Caspase-3 activity confirmed apoptosis sensitivity in mutant protein-expressing neural cells. Conclusions Our study demonstrates that expression of IDH1R132H increases apoptosis susceptibility of neural stem cells and their derivatives. Robust apoptosis causes differentiation deficiency of IDH1R132H-expressing cells. PMID:27145078

Sleep inertia, sleep homeostatic and circadian influences on higher-order cognitive functions.

PubMed

Burke, Tina M; Scheer, Frank A J L; Ronda, Joseph M; Czeisler, Charles A; Wright, Kenneth P

2015-08-01

Sleep inertia, sleep homeostatic and circadian processes modulate cognition, including reaction time, memory, mood and alertness. How these processes influence higher-order cognitive functions is not well known. Six participants completed a 73-day-long study that included two 14-day-long 28-h forced desynchrony protocols to examine separate and interacting influences of sleep inertia, sleep homeostasis and circadian phase on higher-order cognitive functions of inhibitory control and selective visual attention. Cognitive performance for most measures was impaired immediately after scheduled awakening and improved during the first ~2-4 h of wakefulness (decreasing sleep inertia); worsened thereafter until scheduled bedtime (increasing sleep homeostasis); and was worst at ~60° and best at ~240° (circadian modulation, with worst and best phases corresponding to ~09:00 and ~21:00 hours, respectively, in individuals with a habitual wake time of 07:00 hours). The relative influences of sleep inertia, sleep homeostasis and circadian phase depended on the specific higher-order cognitive function task examined. Inhibitory control appeared to be modulated most strongly by circadian phase, whereas selective visual attention for a spatial-configuration search task was modulated most strongly by sleep inertia. These findings demonstrate that some higher-order cognitive processes are differentially sensitive to different sleep-wake regulatory processes. Differential modulation of cognitive functions by different sleep-wake regulatory processes has important implications for understanding mechanisms contributing to performance impairments during adverse circadian phases, sleep deprivation and/or upon awakening from sleep. © 2015 European Sleep Research Society.

Label-free nonlinear optical microscopy detects early markers for osteogenic differentiation of human stem cells.

PubMed

Hofemeier, Arne D; Hachmeister, Henning; Pilger, Christian; Schürmann, Matthias; Greiner, Johannes F W; Nolte, Lena; Sudhoff, Holger; Kaltschmidt, Christian; Huser, Thomas; Kaltschmidt, Barbara

2016-05-26

Tissue engineering by stem cell differentiation is a novel treatment option for bone regeneration. Most approaches for the detection of osteogenic differentiation are invasive or destructive and not compatible with live cell analysis. Here, non-destructive and label-free approaches of Raman spectroscopy, coherent anti-Stokes Raman scattering (CARS) and second harmonic generation (SHG) microscopy were used to detect and image osteogenic differentiation of human neural crest-derived inferior turbinate stem cells (ITSCs). Combined CARS and SHG microscopy was able to detect markers of osteogenesis within 14 days after osteogenic induction. This process increased during continued differentiation. Furthermore, Raman spectroscopy showed significant increases of the PO4(3-) symmetric stretch vibrations at 959 cm(-1) assigned to calcium hydroxyapatite between days 14 and 21. Additionally, CARS microscopy was able to image calcium hydroxyapatite deposits within 14 days following osteogenic induction, which was confirmed by Alizarin Red-Staining and RT- PCR. Taken together, the multimodal label-free analysis methods Raman spectroscopy, CARS and SHG microscopy can monitor osteogenic differentiation of adult human stem cells into osteoblasts with high sensitivity and spatial resolution in three dimensions. Our findings suggest a great potential of these optical detection methods for clinical applications including in vivo observation of bone tissue-implant-interfaces or disease diagnosis.

Label-free nonlinear optical microscopy detects early markers for osteogenic differentiation of human stem cells

NASA Astrophysics Data System (ADS)

Hofemeier, Arne D.; Hachmeister, Henning; Pilger, Christian; Schürmann, Matthias; Greiner, Johannes F. W.; Nolte, Lena; Sudhoff, Holger; Kaltschmidt, Christian; Huser, Thomas; Kaltschmidt, Barbara

2016-05-01

Tissue engineering by stem cell differentiation is a novel treatment option for bone regeneration. Most approaches for the detection of osteogenic differentiation are invasive or destructive and not compatible with live cell analysis. Here, non-destructive and label-free approaches of Raman spectroscopy, coherent anti-Stokes Raman scattering (CARS) and second harmonic generation (SHG) microscopy were used to detect and image osteogenic differentiation of human neural crest-derived inferior turbinate stem cells (ITSCs). Combined CARS and SHG microscopy was able to detect markers of osteogenesis within 14 days after osteogenic induction. This process increased during continued differentiation. Furthermore, Raman spectroscopy showed significant increases of the PO43- symmetric stretch vibrations at 959 cm-1 assigned to calcium hydroxyapatite between days 14 and 21. Additionally, CARS microscopy was able to image calcium hydroxyapatite deposits within 14 days following osteogenic induction, which was confirmed by Alizarin Red-Staining and RT- PCR. Taken together, the multimodal label-free analysis methods Raman spectroscopy, CARS and SHG microscopy can monitor osteogenic differentiation of adult human stem cells into osteoblasts with high sensitivity and spatial resolution in three dimensions. Our findings suggest a great potential of these optical detection methods for clinical applications including in vivo observation of bone tissue-implant-interfaces or disease diagnosis.

Label-free nonlinear optical microscopy detects early markers for osteogenic differentiation of human stem cells

PubMed Central

Hofemeier, Arne D.; Hachmeister, Henning; Pilger, Christian; Schürmann, Matthias; Greiner, Johannes F. W.; Nolte, Lena; Sudhoff, Holger; Kaltschmidt, Christian; Huser, Thomas; Kaltschmidt, Barbara

2016-01-01

Tissue engineering by stem cell differentiation is a novel treatment option for bone regeneration. Most approaches for the detection of osteogenic differentiation are invasive or destructive and not compatible with live cell analysis. Here, non-destructive and label-free approaches of Raman spectroscopy, coherent anti-Stokes Raman scattering (CARS) and second harmonic generation (SHG) microscopy were used to detect and image osteogenic differentiation of human neural crest-derived inferior turbinate stem cells (ITSCs). Combined CARS and SHG microscopy was able to detect markers of osteogenesis within 14 days after osteogenic induction. This process increased during continued differentiation. Furthermore, Raman spectroscopy showed significant increases of the PO43− symmetric stretch vibrations at 959 cm−1 assigned to calcium hydroxyapatite between days 14 and 21. Additionally, CARS microscopy was able to image calcium hydroxyapatite deposits within 14 days following osteogenic induction, which was confirmed by Alizarin Red-Staining and RT- PCR. Taken together, the multimodal label-free analysis methods Raman spectroscopy, CARS and SHG microscopy can monitor osteogenic differentiation of adult human stem cells into osteoblasts with high sensitivity and spatial resolution in three dimensions. Our findings suggest a great potential of these optical detection methods for clinical applications including in vivo observation of bone tissue–implant-interfaces or disease diagnosis. PMID:27225821

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.

Identification of a novel long noncoding RNA that promotes osteoblast differentiation.

PubMed

Nardocci, Gino; Carrasco, Margarita E; Acevedo, Elvis; Hodar, Christian; Meneses, Claudio; Montecino, Martín

2018-05-28

Long noncoding RNAs (lncRNAs) are a heterogeneous class of transcripts, longer than 200 nucleotides, 5'-capped, polyadenylated, and poorly conserved among mammalian species. Several studies have shown the contribution of lncRNAs to different cellular processes, including regulation of the chromatin structure, control of messenger RNA translation, regulation of gene transcription, regulation of embryonic pluripotency, and differentiation. Although limited numbers of functional lncRNAs have been identified so far, the immense regulatory potential of these RNAs is already evident, indicating that a functional characterization of lncRNAs is needed. In this study, mouse preosteoblastic cells were induced to differentiate into osteoblasts. At 3 sequential differentiation stages, total RNA was isolated and libraries were constructed for Illumina sequencing. The resulting sequences were aligned and transcript abundances were determined. New lncRNA candidates that displayed differential expression patterns during osteoblast differentiation were identified by combining bioinformatics and reverse transcription polymerase chain reaction analyses. Among these, lncRNA-1 that exhibited increased expression during osteogenesis and was downregulated during myogenesis. Importantly, knockdown of lncRNA-1 expression in primary mouse preosteoblasts was found to inhibit osteogenic differentiation, reflected by a reduced transcription of the Runx2/p57 and Sp7 bone master genes. Together, our results indicate that lncRNA-1 represents a new regulatory RNA that plays a relevant role during the early stages of osteogenesis. © 2018 Wiley Periodicals, Inc.

Cell Expansion During Directed Differentiation of Stem Cells Toward the Hepatic Lineage

PubMed Central

Raju, Ravali; Chau, David; Cho, Dong Seong; Park, Yonsil; Verfaillie, Catherine M.

2017-01-01

The differentiation of human pluripotent stem cells toward the hepatocyte lineage can potentially provide an unlimited source of functional hepatocytes for transplantation and extracorporeal bioartificial liver applications. It is anticipated that the quantities of cells needed for these applications will be in the order of 109–1010 cells, because of the size of the liver. An ideal differentiation protocol would be to enable directed differentiation to the hepatocyte lineage with simultaneous cell expansion. We introduced a cell expansion stage after the commitment of human embryonic stem cells to the endodermal lineage, to allow for at least an eightfold increase in cell number, with continuation of cell maturation toward the hepatocyte lineage. The progressive changes in the transcriptome were measured by expression array, and the expression dynamics of certain lineage markers was measured by mass cytometry during the differentiation and expansion process. The findings revealed that while cells were expanding they were also capable of progressing in their differentiation toward the hepatocyte lineage. In addition, our transcriptome, protein and functional studies, including albumin secretion, drug-induced CYP450 expression and urea production, all indicated that the hepatocyte-like cells obtained with or without cell expansion are very similar. This method of simultaneous cell expansion and hepatocyte differentiation should facilitate obtaining large quantities of cells for liver cell applications. PMID:27806669

Optimal segmentation and packaging process

DOEpatents

Kostelnik, Kevin M.; Meservey, Richard H.; Landon, Mark D.

1999-01-01

A process for improving packaging efficiency uses three dimensional, computer simulated models with various optimization algorithms to determine the optimal segmentation process and packaging configurations based on constraints including container limitations. The present invention is applied to a process for decontaminating, decommissioning (D&D), and remediating a nuclear facility involving the segmentation and packaging of contaminated items in waste containers in order to minimize the number of cuts, maximize packaging density, and reduce worker radiation exposure. A three-dimensional, computer simulated, facility model of the contaminated items are created. The contaminated items are differentiated. The optimal location, orientation and sequence of the segmentation and packaging of the contaminated items is determined using the simulated model, the algorithms, and various constraints including container limitations. The cut locations and orientations are transposed to the simulated model. The contaminated items are actually segmented and packaged. The segmentation and packaging may be simulated beforehand. In addition, the contaminated items may be cataloged and recorded.

The effects of mutational processes and selection on driver mutations across cancer types.

PubMed

Temko, Daniel; Tomlinson, Ian P M; Severini, Simone; Schuster-Böckler, Benjamin; Graham, Trevor A

2018-05-10

Epidemiological evidence has long associated environmental mutagens with increased cancer risk. However, links between specific mutation-causing processes and the acquisition of individual driver mutations have remained obscure. Here we have used public cancer sequencing data from 11,336 cancers of various types to infer the independent effects of mutation and selection on the set of driver mutations in a cancer type. First, we detect associations between a range of mutational processes, including those linked to smoking, ageing, APOBEC and DNA mismatch repair (MMR) and the presence of key driver mutations across cancer types. Second, we quantify differential selection between well-known alternative driver mutations, including differences in selection between distinct mutant residues in the same gene. These results show that while mutational processes have a large role in determining which driver mutations are present in a cancer, the role of selection frequently dominates.

Pluripotency, Differentiation, and Reprogramming: A Gene Expression Dynamics Model with Epigenetic Feedback Regulation

PubMed Central

Miyamoto, Tadashi; Furusawa, Chikara; Kaneko, Kunihiko

2015-01-01

Embryonic stem cells exhibit pluripotency: they can differentiate into all types of somatic cells. Pluripotent genes such as Oct4 and Nanog are activated in the pluripotent state, and their expression decreases during cell differentiation. Inversely, expression of differentiation genes such as Gata6 and Gata4 is promoted during differentiation. The gene regulatory network controlling the expression of these genes has been described, and slower-scale epigenetic modifications have been uncovered. Although the differentiation of pluripotent stem cells is normally irreversible, reprogramming of cells can be experimentally manipulated to regain pluripotency via overexpression of certain genes. Despite these experimental advances, the dynamics and mechanisms of differentiation and reprogramming are not yet fully understood. Based on recent experimental findings, we constructed a simple gene regulatory network including pluripotent and differentiation genes, and we demonstrated the existence of pluripotent and differentiated states from the resultant dynamical-systems model. Two differentiation mechanisms, interaction-induced switching from an expression oscillatory state and noise-assisted transition between bistable stationary states, were tested in the model. The former was found to be relevant to the differentiation process. We also introduced variables representing epigenetic modifications, which controlled the threshold for gene expression. By assuming positive feedback between expression levels and the epigenetic variables, we observed differentiation in expression dynamics. Additionally, with numerical reprogramming experiments for differentiated cells, we showed that pluripotency was recovered in cells by imposing overexpression of two pluripotent genes and external factors to control expression of differentiation genes. Interestingly, these factors were consistent with the four Yamanaka factors, Oct4, Sox2, Klf4, and Myc, which were necessary for the establishment of induced pluripotent stem cells. These results, based on a gene regulatory network and expression dynamics, contribute to our wider understanding of pluripotency, differentiation, and reprogramming of cells, and they provide a fresh viewpoint on robustness and control during development. PMID:26308610

Mirna biogenesis pathway is differentially regulated during adipose derived stromal/stem cell differentiation.

PubMed

Martin, E C; Qureshi, A T; Llamas, C B; Burow, M E; King, A G; Lee, O C; Dasa, V; Freitas, M A; Forsberg, J A; Elster, E A; Davis, T A; Gimble, J M

2018-02-07

Stromal/stem cell differentiation is controlled by a vast array of regulatory mechanisms. Included within these are methods of mRNA gene regulation that occur at the level of epigenetic, transcriptional, and/or posttranscriptional modifications. Current studies that evaluate the posttranscriptional regulation of mRNA demonstrate microRNAs (miRNAs) as key mediators of stem cell differentiation through the inhibition of mRNA translation. miRNA expression is enhanced during both adipogenic and osteogenic differentiation; however, the mechanism by which miRNA expression is altered during stem cell differentiation is less understood. Here we demonstrate for the first time that adipose-derived stromal/stem cells (ASCs) induced to an adipogenic or osteogenic lineage have differences in strand preference (-3p and -5p) for miRNAs originating from the same primary transcript. Furthermore, evaluation of miRNA expression in ASCs demonstrates alterations in both miRNA strand preference and 5'seed site heterogeneity. Additionally, we show that during stem cell differentiation there are alterations in expression of genes associated with the miRNA biogenesis pathway. Quantitative RT-PCR demonstrated changes in the Argonautes (AGO1-4), Drosha, and Dicer at intervals of ASC adipogenic and osteogenic differentiation compared to untreated ASCs. Specifically, we demonstrated altered expression of the AGOs occurring during both adipogenesis and osteogenesis, with osteogenesis increasing AGO1-4 expression and adipogenesis decreasing AGO1 gene and protein expression. These data demonstrate changes to components of the miRNA biogenesis pathway during stromal/stem cell differentiation. Identifying regulatory mechanisms for miRNA processing during ASC differentiation may lead to novel mechanisms for the manipulation of lineage differentiation of the ASC through the global regulation of miRNA as opposed to singular regulatory mechanisms.

Differential proteome analysis of the cell differentiation regulated by BCC, CRH, CXCR4, GnRH, GPCR, IL1 signaling pathways in Chinese fire-bellied newt limb regeneration.

PubMed

Geng, Xiaofang; Xu, Tiantian; Niu, Zhipeng; Zhou, Xiaochun; Zhao, Lijun; Xie, Zhaohui; Xue, Deming; Zhang, Fuchun; Xu, Cunshuan

2014-01-01

Following amputation, the newt has the remarkable ability to regenerate its limb, and this process involves dedifferentiation, proliferation and differentiation. To investigate the potential proteome during a dynamic network of Chinese fire-bellied newt limb regeneration (CNLR), two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and mass spectrum (MS) were applied to examine changes in the proteome that occurred at 11 time points after amputation. Meanwhile, several proteins were selected to validate their expression levels by Western blot. The results revealed that 1476 proteins had significantly changed as compared to the control group. Gene Ontology annotation and protein network analysis by Ingenuity Pathway Analysis 9.0 (IPA) software suggested that the differentially expressed proteins were involved in 33 kinds of physiological activities including signal transduction, cell proliferation, cell differentiation, etc. Among these proteins, 407 proteins participated in cell differentiation with 212 proteins in the differentiation of skin cell, myocyte, neurocyte, chondrocyte and osteocyte, and 37 proteins participated in signaling pathways of BCC, CRH, CXCR4, GnRH, GPCR and IL1 which regulated cell differentiation and redifferentiation. On the other hand, the signal transduction activity and cell differentiation activity were analyzed by IPA based on the changes in the expression of these proteins. The results showed that BCC, CRH, CXCR4, GnRH, GPCR and IL1 signaling pathways played an important role in regulating the differentiation of skin cell, myocyte, neurocyte, chondrocyte and osteocyte during CNLR. Copyright © 2014 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Carbon monoxide improves neuronal differentiation and yield by increasing the functioning and number of mitochondria.

PubMed

Almeida, Ana S; Sonnewald, Ursula; Alves, Paula M; Vieira, Helena L A

2016-08-01

The process of cell differentiation goes hand-in-hand with metabolic adaptations, which are needed to provide energy and new metabolites. Carbon monoxide (CO) is an endogenous cytoprotective molecule able to inhibit cell death and improve mitochondrial metabolism. Neuronal differentiation processes were studied using the NT2 cell line, which is derived from human testicular embryonic teratocarcinoma and differentiates into post-mitotic neurons upon retinoic acid treatment. CO-releasing molecule A1 (CORM-A1) was used do deliver CO into cell culture. CO treatment improved NT2 neuronal differentiation and yield, since there were more neurons and the total cell number increased following the differentiation process. CO supplementation enhanced the mitochondrial population in post-mitotic neurons derived from NT2 cells, as indicated by an increase in mitochondrial DNA. CO treatment during neuronal differentiation increased the extent of the classical metabolic change that occurs during neuronal differentiation, from glycolytic to more oxidative metabolism, by decreasing the ratio of lactate production and glucose consumption. The expression of pyruvate and lactate dehydrogenases was higher, indicating an augmented oxidative metabolism. Moreover, these findings were corroborated by an increased percentage of (13) C incorporation from [U-(13) C]glucose into the tricarboxylic acid cycle metabolites malate and citrate, and also glutamate and aspartate in CO-treated cells. Finally, under low levels of oxygen (5%), which enhances glycolytic metabolism, some of the enhancing effects of CO on mitochondria were not observed. In conclusion, our data show that CO improves neuronal and mitochondrial yield by stimulation of tricarboxylic acid cycle activity, and thus oxidative metabolism of NT2 cells during the process of neuronal differentiation. The process of cell differentiation is coupled with metabolic adaptations. Carbon monoxide (CO) is an endogenous cytoprotective gasotransmitter able to prevent cell death and improve mitochondrial metabolism. Herein CO supplementation improved neuronal differentiation yield, by enhancing mitochondrial population and promoting the classical metabolic change that occurs during neuronal differentiation, from glycolytic to oxidative metabolism. © 2016 International Society for Neurochemistry.

Oxygen-controlled automated neural differentiation of mouse embryonic stem cells.

PubMed

Mondragon-Teran, Paul; Tostoes, Rui; Mason, Chris; Lye, Gary J; Veraitch, Farlan S

2013-03-01

Automation and oxygen tension control are two tools that provide significant improvements to the reproducibility and efficiency of stem cell production processes. the aim of this study was to establish a novel automation platform capable of controlling oxygen tension during both the cell-culture and liquid-handling steps of neural differentiation processes. We built a bespoke automation platform, which enclosed a liquid-handling platform in a sterile, oxygen-controlled environment. An airtight connection was used to transfer cell culture plates to and from an automated oxygen-controlled incubator. Our results demonstrate that our system yielded comparable cell numbers, viabilities, metabolism profiles and differentiation efficiencies when compared with traditional manual processes. Interestingly, eliminating exposure to ambient conditions during the liquid-handling stage resulted in significant improvements in the yield of MAP2-positive neural cells, indicating that this level of control can improve differentiation processes. This article describes, for the first time, an automation platform capable of maintaining oxygen tension control during both the cell-culture and liquid-handling stages of a 2D embryonic stem cell differentiation process.

Cells differentiated from mouse embryonic stem cells via embryoid bodies express renal marker molecules.

PubMed

Kramer, Jan; Steinhoff, Jürgen; Klinger, Matthias; Fricke, Lutz; Rohwedel, Jürgen

2006-03-01

Differentiation of mouse embryonic stem (ES) cells via embryoid bodies (EB) is established as a suitable model to study cellular processes of development in vitro. ES cells are known to be pluripotent because of their capability to differentiate into cell types of all three germ layers including germ cells. Here, we show that ES cells differentiate into renal cell types in vitro. We found that genes were expressed during EB cultivation, which have been previously described to be involved in renal development. Marker molecules characteristic for terminally differentiated renal cell types were found to be expressed predominantly during late stages of EB cultivation, while marker molecules involved in the initiation of nephrogenesis were already expressed during early steps of EB development. On the cellular level--using immunostaining--we detected cells expressing podocin, nephrin and wt-1, characteristic for differentiated podocytes and other cells, which expressed Tamm-Horsfall protein, a marker for distal tubule epithelial cells of kidney tissue. Furthermore, the proximal tubule marker molecules renal-specific oxido reductase, kidney androgen-related protein and 25-hydroxyvitamin D3alpha-hydroxylase were found to be expressed in EBs. In particular, we could demonstrate that cells expressing podocyte marker molecules assemble to distinct ring-like structures within the EBs. Because the differentiation efficiency into these cell types is still relatively low, application of fibroblast growth factor (FGF)-2 in combination with leukaemia inhibitory factor was tested for induction, but did not enhance ES cell-derived renal differentiation in vitro.

Cell Fate and Differentiation of the Developing Ocular Lens

PubMed Central

Greiling, Teri M. S.; Aose, Masamoto

2010-01-01

Purpose. Even though zebrafish development does not include the formation of a lens vesicle, the authors' hypothesis is that the processes of cell differentiation are similar in zebrafish and mammals and determine cell fates in the lens. Methods. Two-photon live embryo imaging was used to follow individual fluorescently labeled cells in real-time from the placode stage at 16 hours postfertilization (hpf) until obvious morphologic differentiation into epithelium or fiber cells had occurred at approximately 28 hpf. Immunohistochemistry was used to label proliferating, differentiating, and apoptotic cells. Results. Similar to the mammal, cells in the teleost peripheral lens placode migrated to the anterior lens mass and differentiated into an anterior epithelium. Cells in the central lens placode migrated to the posterior lens mass and differentiated into primary fiber cells. Anterior and posterior polarization in the zebrafish lens mass was similar to mammalian lens vesicle polarization. Primary fiber cell differentiation was apparent at approximately 21 hpf, before separation of the lens from the surface ectoderm, as evidenced by cell elongation, exit from the cell cycle, and expression of Zl-1, a marker for fiber differentiation. TUNEL labeling demonstrated that apoptosis was not a primary mechanism for lens separation from the surface ectoderm. Conclusions. Despite the absence of a lens vesicle in the zebrafish embryo, lens organogenesis appears to be well conserved among vertebrates. Results using three-dimensional live embryo imaging of zebrafish development showed minimal differences and strong similarities in the fate of cells in the zebrafish and mammalian lens placode. PMID:19834024

Dissecting Stages of Human Kidney Development and Tumorigenesis with Surface Markers Affords Simple Prospective Purification of Nephron Stem Cells.

PubMed

Pode-Shakked, Naomi; Pleniceanu, Oren; Gershon, Rotem; Shukrun, Rachel; Kanter, Itamar; Bucris, Efrat; Pode-Shakked, Ben; Tam, Gal; Tam, Hadar; Caspi, Revital; Pri-Chen, Sara; Vax, Einav; Katz, Guy; Omer, Dorit; Harari-Steinberg, Orit; Kalisky, Tomer; Dekel, Benjamin

2016-03-29

When assembling a nephron during development a multipotent stem cell pool becomes restricted as differentiation ensues. A faulty differentiation arrest in this process leads to transformation and initiation of a Wilms' tumor. Mapping these transitions with respective surface markers affords accessibility to specific cell subpopulations. NCAM1 and CD133 have been previously suggested to mark human renal progenitor populations. Herein, using cell sorting, RNA sequencing, in vitro studies with serum-free media and in vivo xenotransplantation we demonstrate a sequential map that links human kidney development and tumorigenesis; In nephrogenesis, NCAM1(+)CD133(-) marks SIX2(+) multipotent renal stem cells transiting to NCAM1(+)CD133(+) differentiating segment-specific SIX2(-) epithelial progenitors and NCAM1(-)CD133(+) differentiated nephron cells. In tumorigenesis, NCAM1(+)CD133(-) marks SIX2(+) blastema that includes the ALDH1(+) WT cancer stem/initiating cells, while NCAM1(+)CD133(+) and NCAM1(-)CD133(+) specifying early and late epithelial differentiation, are severely restricted in tumor initiation capacity and tumor self-renewal. Thus, negative selection for CD133 is required for defining NCAM1(+) nephron stem cells in normal and malignant nephrogenesis.

Syndecan-4 Regulates Muscle Differentiation and Is Internalized from the Plasma Membrane during Myogenesis.

PubMed

Rønning, Sissel B; Carlson, Cathrine R; Stang, Espen; Kolset, Svein O; Hollung, Kristin; Pedersen, Mona E

2015-01-01

The cell surface proteoglycan syndecan-4 has been reported to be crucial for muscle differentiation, but the molecular mechanisms still remain to be fully understood. During in vitro differentiation of bovine muscle cells immunocytochemical analyses showed strong labelling of syndecan-4 intracellularly, in close proximity with Golgi structures, in membranes of intracellular vesicles and finally, in the nuclear area including the nuclear envelope. Chase experiments showed that syndecan-4 was internalized from the plasma membrane during this process. Furthermore, when syndecan-4 was knocked down by siRNA more myotubes were formed, and the expression of myogenic transcription factors, β1-integrin and actin was influenced. However, when bovine muscle cells were treated with a cell-penetrating peptide containing the cytoplasmic region of syndecan-4, myoblast fusion and thus myotube formation was blocked, both in normal cells and in syndecan-4 knock down cells. Altogether this suggests that the cytoplasmic domain of syndecan-4 is important in regulation of myogenesis. The internalization of syndecan-4 from the plasma membrane during muscle differentiation and the nuclear localization of syndecan-4 in differentiated muscle cells may be part of this regulation, and is a novel aspect of syndecan biology which merits further studies.

Arginine methylation catalyzed by PRMT1 is required for B cell activation and differentiation.

PubMed

Infantino, Simona; Light, Amanda; O'Donnell, Kristy; Bryant, Vanessa; Avery, Danielle T; Elliott, Michael; Tangye, Stuart G; Belz, Gabrielle; Mackay, Fabienne; Richard, Stephane; Tarlinton, David

2017-10-12

Arginine methylation catalyzed by protein arginine methyltransferases (PRMT) is a common post-translational modification in mammalian cells, regulating many important functions including cell signalling, proliferation and differentiation. Here we show the role of PRMT1 in B-cell activation and differentiation. PRMT1 expression and activity in human and mouse peripheral B cells increases in response to in vitro or in vivo activation. Deletion of the Prmt1 gene in mature B cells establishes that although the frequency and phenotype of peripheral B cell subsets seem unaffected, immune responses to T-cell-dependent and -independent antigens are substantially reduced. In vitro activation of Prmt1-deficient B cells with a variety of mitogens results in diminished proliferation, differentiation and survival, effects that are correlated with altered signal transduction from the B cell receptor. Thus PRMT1 activity in B cells is required for correct execution of multiple processes that in turn are necessary for humoral immunity.PRMT1 is an arginine methyltransferase involved in a variety of cell functions. Here the authors delete PRMT1 specifically in mature B cells to show the importance of arginine methylation for B cell proliferation, differentiation and survival, and thereby for humoral immunity.

Pigment Cell Differentiation in Sea Urchin Blastula-Derived Primary Cell Cultures

PubMed Central

Ageenko, Natalya V.; Kiselev, Konstantin V.; Dmitrenok, Pavel S.; Odintsova, Nelly A.

2014-01-01

The quinone pigments of sea urchins, specifically echinochrome and spinochromes, are known for their effective antioxidant, antibacterial, antifungal, and antitumor activities. We developed in vitro technology for inducing pigment differentiation in cell culture. The intensification of the pigment differentiation was accompanied by a simultaneous decrease in cell proliferation. The number of pigment cells was two-fold higher in the cells cultivated in the coelomic fluids of injured sea urchins than in those intact. The possible roles of the specific components of the coelomic fluids in the pigment differentiation process and the quantitative measurement of the production of naphthoquinone pigments during cultivation were examined by MALDI and electrospray ionization mass spectrometry. Echinochrome A and spinochrome E were produced by the cultivated cells of the sand dollar Scaphechinus mirabilis in all tested media, while only spinochromes were found in the cultivated cells of another sea urchin, Strongylocentrotus intermedius. The expression of genes associated with the induction of pigment differentiation was increased in cells cultivated in the presence of shikimic acid, a precursor of naphthoquinone pigments. Our results should contribute to the development of new techniques in marine biotechnology, including the generation of cell cultures producing complex bioactive compounds with therapeutic potential. PMID:24979272

A novel bioactive osteogenesis scaffold delivers ascorbic acid, β-glycerophosphate, and dexamethasone in vivo to promote bone regeneration.

PubMed

Wang, Chao; Cao, Xuecheng; Zhang, Yongxian

2017-05-09

Ascorbic acid, β-glycerophosphate, and dexamethasone have been used in osteogenesis differentiation medium for in vitro cell culture, nothing is known for delivering these three bioactive compounds in vivo. In this study, we synthesized a novel bioactive scaffold by combining these three compounds with a lysine diisocyanate-based polyurethane. These bioactive compounds were released from the scaffold during the degradation process. The cell culture showed that the sponge-like structure in the scaffold was critical in providing a large surface area to support cell growth and all degradation products of the polymer were non-toxic. This bioactive scaffold enhanced the bone regeneration as evidenced by increasing the expression of three bone-related genes including collagen type I, Runx-2 and osteocalcin in rabbit bone marrow stem cells (BMSCs) in vitro and in vivo. The osteogenesis differentiation of BMSCs cultured in this bioactive scaffold was similar to that in osteogenesis differentiation medium and more extensive in this bioactive scaffold compared to the scaffold without these three bioactive compounds. These results indicated that the scaffold containing three bioactive compounds was a good osteogenesis differentiation promoter to enhance the osteogenesis differentiation and new bone formation in vivo.

A novel bioactive osteogenesis scaffold delivers ascorbic acid, β-glycerophosphate, and dexamethasone in vivo to promote bone regeneration

PubMed Central

Wang, Chao; Cao, Xuecheng; Zhang, Yongxian

2017-01-01

Ascorbic acid, β-glycerophosphate, and dexamethasone have been used in osteogenesis differentiation medium for in vitro cell culture, nothing is known for delivering these three bioactive compounds in vivo. In this study, we synthesized a novel bioactive scaffold by combining these three compounds with a lysine diisocyanate-based polyurethane. These bioactive compounds were released from the scaffold during the degradation process. The cell culture showed that the sponge-like structure in the scaffold was critical in providing a large surface area to support cell growth and all degradation products of the polymer were non-toxic. This bioactive scaffold enhanced the bone regeneration as evidenced by increasing the expression of three bone-related genes including collagen type I, Runx-2 and osteocalcin in rabbit bone marrow stem cells (BMSCs) in vitro and in vivo. The osteogenesis differentiation of BMSCs cultured in this bioactive scaffold was similar to that in osteogenesis differentiation medium and more extensive in this bioactive scaffold compared to the scaffold without these three bioactive compounds. These results indicated that the scaffold containing three bioactive compounds was a good osteogenesis differentiation promoter to enhance the osteogenesis differentiation and new bone formation in vivo. PMID:28404942

Reactive oxygen species and oxidative stress in osteoclastogenesis, skeletal aging and bone diseases.

PubMed

Callaway, Danielle A; Jiang, Jean X

2015-07-01

Osteoclasts are cells derived from bone marrow macrophages and are important in regulating bone resorption during bone homeostasis. Understanding what drives osteoclast differentiation and activity is important when studying diseases characterized by heightened bone resorption relative to formation, such as osteoporosis. In the last decade, studies have indicated that reactive oxygen species (ROS), including superoxide and hydrogen peroxide, are crucial components that regulate the differentiation process of osteoclasts. However, there are still many unanswered questions that remain. This review will examine the mechanisms by which ROS can be produced in osteoclasts as well as how it may affect osteoclast differentiation and activity through its actions on osteoclastogenesis signaling pathways. In addition, the contribution of ROS to the aging-associated disease of osteoporosis will be addressed and how targeting ROS may lead to the development of novel therapeutic treatment options.

ERP-based detection of brain pathology in rat models for preclinical Alzheimer's disease

NASA Astrophysics Data System (ADS)

Nouriziabari, Seyed Berdia

Early pathological features of Alzheimer's disease (AD) include the accumulation of hyperphosphorylated tau protein (HP-tau) in the entorhinal cortex and progressive loss of basal forebrain (BF) cholinergic neurons. These pathologies are known to remain asymptomatic for many years before AD is clinically diagnosed; however, they may induce aberrant brain processing which can be captured as an abnormality in event-related potentials (ERPs). Here, we examined cortical ERPs while a differential associative learning paradigm was applied to adult male rats with entorhinal HP-tau, pharmacological blockade of muscarinic acetylcholine receptors, or both conditions. Despite no impairment in differential associative and reversal learning, each pathological feature induced distinct abnormality in cortical ERPs to an extent that was sufficient for machine classifiers to accurately detect a specific type of pathology based on these ERP features. These results highlight a potential use of ERPs during differential associative learning as a biomarker for asymptomatic AD pathology.

T follicular helper cell differentiation, function, and roles in disease

PubMed Central

Crotty, Shane

2014-01-01

Summary Follicular helper T (Tfh) cells are specialized providers of T cell help to B cells, and are essential for germinal center formation, affinity maturation, and the development of most high affinity antibodies and memory B cells. Tfh cell differentiation is a multi-stage, multi-factorial process involving B cell lymphoma 6 (Bcl6) and other transcription factors. This article reviews understanding of Tfh cell biology, including their differentiation, migration, transcriptional regulation, and B cell help functions. Tfh cells are critical components of many protective immune responses against pathogens. As such, there is strong interest in harnessing Tfh cells to improve vaccination strategies. Tfh cells also have roles in a range of other diseases, particularly autoimmune diseases. Overall, there have been dramatic advances in this young field, but there is much to be learned about Tfh cell biology in the interest of applying that knowledge to biomedical needs. PMID:25367570

Of Hissing Snakes and Angry Voices: Human Infants Are Differentially Responsive to Evolutionary Fear-Relevant Sounds

ERIC Educational Resources Information Center

Erlich, Nicole; Lipp, Ottmar V.; Slaughter, Virginia

2013-01-01

Adult humans demonstrate differential processing of stimuli that were recurrent threats to safety and survival throughout evolutionary history. Recent studies suggest that differential processing of evolutionarily ancient threats occurs in human infants, leading to the proposal of an inborn mechanism for rapid identification of, and response to,…

Dynamic and differential expression of the gonadal aromatase during the process of sexual differentiation in a novel transgenic cyp19a1a-eGFP zebrafish line.

PubMed

Hinfray, Nathalie; Sohm, Frédéric; Caulier, Morgane; Chadili, Edith; Piccini, Benjamin; Torchy, Camille; Porcher, Jean-Marc; Guiguen, Yann; Brion, François

2018-05-15

In zebrafish, there exists a clear need for new tools to study sex differentiation dynamic and its perturbation by endocrine disrupting chemicals. In this context, we developed and characterized a novel transgenic zebrafish line expressing green fluorescent protein (GFP) under the control of the zebrafish cyp19a1a (gonadal aromatase) promoter. In most gonochoristic fish species including zebrafish, cyp19a1a, the enzyme responsible for the synthesis of estrogens, has been shown to play a critical role in the processes of reproduction and sexual differentiation. This novel cyp19a1a-eGFP transgenic line allowed a deeper characterization of expression and localization of cyp19a1a gene in zebrafish gonads both at the adult stage and during development. At the adult stage, GFP expression was higher in ovaries than in testis. We showed a perfect co-expression of GFP and endogenous Cyp19a1a protein in gonads that was mainly localized in the cytoplasm of peri-follicular cells in the ovary and of Leydig and germ cells in the testis. During development, GFP was expressed in all immature gonads of 20 dpf-old zebrafish. Then, GFP expression increased in early differentiated female at 30 and 35dpf to reach a high GFP intensity in well-differentiated ovaries at 40dpf. On the contrary, males consistently displayed low GFP expression as compared to female whatever their stage of development, resulting in a clear dimorphic expression between both sexes. Interestingly, fish that undergoes ovary-to-testis transition (35 and 40dpf) presented GFP levels similar to males or intermediate between females and males. In this transgenic line our results confirm that cyp19a1a is expressed early during development, before the histological differentiation of the gonads, and that the down-regulation of cyp19a1a expression is likely responsible for the testicular differentiation. Moreover, we show that although cyp19a1a expression exhibits a clear dimorphic expression pattern in gonads during sexual differentiation, its expression persists whatever the sex suggesting that estradiol synthesis is important for gonadal development of both sexes. Monitoring the expression of GFP in control and exposed-fish will help determine the sensitivity of this transgenic line to EDCs and to refine mechanistic based-assays for the study of EDCs. In fine, this transgenic zebrafish line will be a useful tool to study physiological processes such as reproduction and sexual differentiation, and their perturbations by EDCs. Copyright © 2017 Elsevier Inc. All rights reserved.

Integrated processes for expansion and differentiation of human pluripotent stem cells in suspended microcarriers cultures

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

Lam, Alan Tin-Lun, E-mail: alan_lam@bti.a-star.edu.sg; Chen, Allen Kuan-Liang; Ting, Sherwin Qi-Peng

Current methods for human pluripotent stem cells (hPSC) expansion and differentiation can be limited in scalability and costly (due to their labor intensive nature). This can limit their use in cell therapy, drug screening and toxicity assays. One of the approaches that can overcome these limitations is microcarrier (MC) based cultures in which cells are expanded as cell/MC aggregates and then directly differentiated as embryoid bodies (EBs) in the same agitated reactor. This integrated process can be scaled up and eliminate the need for some culture manipulation used in common monolayer and EBs cultures. This review describes the principles ofmore » such microcarriers based integrated hPSC expansion and differentiation process, and parameters that can affect its efficiency (such as MC type and extracellular matrix proteins coatings, cell/MC aggregates size, and agitation). Finally examples of integrated process for generation cardiomyocytes (CM) and neural progenitor cells (NPC) as well as challenges to be solved are described. - Highlights: • Expansion of hPSC on microcarriers. • Differentiation of hPSC on microcarriers. • Parameters that can affect the expansion and differentiation of hPSC on microcarriers. • Integration of expansion and differentiation of hPSC on microcarriers in one unit operation.« less

Developmental and Cognitive Perspectives on Humans' Sense of the Times of Past and Future Events

ERIC Educational Resources Information Center

Friedman, W.J.

2005-01-01

Mental time travel in human adults includes a sense of when past events occurred and future events are expected to occur. Studies with adults and children reveal that a number of distinct psychological processes contribute to a temporally differentiated sense of the past and future. Adults possess representations of multiple time patterns, and…

Integro-differential equation analysis and radioisotope imaging systems. Research proposal. [Testing of radioisotope imaging system in phantoms

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

Hart, H.

1976-03-09

Design modifications of a five-probe focusing collimator coincidence radioisotope scanning system are described. Clinical applications of the system were tested in phantoms using radioisotopes with short biological half-lives, including /sup 75/Se, /sup 192/Ir, /sup 43/K, /sup 130/I, and /sup 82/Br. Data processing methods are also described. (CH)

Simulating aerial gravitropism and posture control in plants: what has been done, what is missing

NASA Astrophysics Data System (ADS)

Coutand, Catherine; Pot, Guillaume; Bastien, R.; Badel, Eric; Moulia, Bruno

The gravitropic response requires a process of perception of the signal and a motor process to actuate the movements. Different models have been developed, some focuses on the perception process and some focuses on the motor process. The kinematics of the gravitropic response will be first detailed to set the phenomenology of gravi- and auto-tropism. A model of perception (AC model) will be first presented to demonstrate that sensing inclination is not sufficient to control the gravitropic movement, and that proprioception is also involved. Then, “motor models” will be reviewed. In herbaceous plants, differential growth is the main motor. Modelling tropic movements with simulating elongation raises some difficulties that will be explained. In woody structures the main motor process is the differentiation of reaction wood via cambial growth. We will first present the simplest biomechanical model developed to simulate gravitropism and its limits will be pointed out. Then a more sophisticated model (TWIG) will be presented with a special focus on the importance of wood viscoelasticity and the wood maturation process and its regulation by a mechanosensing process. The presentation will end by a balance sheet of what is done and what is missing for a complete modelling of gravitropism and will present first results of a running project dedicating to get the data required to include phototropism in the actual models.

Understanding Neurological Disease Mechanisms in the Era of Epigenetics

PubMed Central

Qureshi, Irfan A.; Mehler, Mark F.

2015-01-01

The burgeoning field of epigenetics is making a significant impact on our understanding of brain evolution, development, and function. In fact, it is now clear that epigenetic mechanisms promote seminal neurobiological processes, ranging from neural stem cell maintenance and differentiation to learning and memory. At the molecular level, epigenetic mechanisms regulate the structure and activity of the genome in response to intracellular and environmental cues, including the deployment of cell type–specific gene networks and those underlying synaptic plasticity. Pharmacological and genetic manipulation of epigenetic factors can, in turn, induce remarkable changes in neural cell identity and cognitive and behavioral phenotypes. Not surprisingly, it is also becoming apparent that epigenetics is intimately involved in neurological disease pathogenesis. Herein, we highlight emerging paradigms for linking epigenetic machinery and processes with neurological disease states, including how (1) mutations in genes encoding epigenetic factors cause disease, (2) genetic variation in genes encoding epigenetic factors modify disease risk, (3) abnormalities in epigenetic factor expression, localization, or function are involved in disease pathophysiology, (4) epigenetic mechanisms regulate disease-associated genomic loci, gene products, and cellular pathways, and (5) differential epigenetic profiles are present in patient-derived central and peripheral tissues. PMID:23571666

Notochord-derived BMP antagonists inhibit endothelial cell generation and network formation.

PubMed

Bressan, Michael; Davis, Patricia; Timmer, John; Herzlinger, Doris; Mikawa, Takashi

2009-02-01

Embryonic blood vessel formation is initially mediated through the sequential differentiation, migration, and assembly of endothelial cells (ECs). While many molecular signals that promote vascular development have been identified, little is known about suppressors of this process. In higher vertebrates, including birds and mammals, the vascular network forms throughout the embryonic disk with the exception of a region along the midline. We have previously shown that the notochord is responsible for the generation and maintenance of the avascular midline and that BMP antagonists expressed by this embryonic tissue, including Noggin and Chordin, can mimic this inhibitory role. Here we report that the notochord suppresses the generation of ECs from the mesoderm both in vivo and in vitro. We also report that the notochord diminishes the ability of mature ECs to organize into a primitive plexus. Furthermore, Noggin mimics notochord-based inhibition by preventing mesodermal EC generation and mature EC network formation. These findings suggest that the mesoderm surrounding the midline is competent to give rise to ECs and to form blood vessels, but that notochord derived-BMP antagonists suppress EC differentiation and maturation processes leading to inhibition of midline vessel formation.

Divergent Relationship of Depression Severity to Social Reward Responses Among Patients with Bipolar Versus Unipolar Depression

PubMed Central

Sharma, Anup; Satterthwaite, Theodore D.; Vandekar, Lillie; Katchmar, Natalie; Daldal, Aylin; Ruparel, Kosha; A.Elliott, Mark; Baldassano, Claudia; Thase, Michael E.; Gur, Raquel E.; Kable, Joseph W.; Wolf, Daniel H.

2016-01-01

Neuroimaging studies of mood disorders demonstrate abnormalities in brain regions implicated in reward processing. However, there is a paucity of research investigating how social rewards affect reward circuit activity in these disorders. Here, we evaluated the relationship of both diagnostic category and dimensional depression severity to reward system function in bipolar and unipolar depression. In total, 86 adults were included, including 24 patients with bipolar depression, 24 patients with unipolar depression, and 38 healthy comparison subjects. Participants completed a social reward task during 3T BOLD fMRI. On average, diagnostic groups did not differ in activation to social reward. However, greater depression severity significantly correlated with reduced bilateral ventral striatum activation to social reward in the bipolar depressed group, but not the unipolar depressed group. In addition, decreased left orbitofrontal cortical activation correlated with more severe symptoms in bipolar depression, but not unipolar depression. These differential dimensional effects resulted in a significant voxelwise group by depression severity interaction. Taken together, these results provide initial evidence that deficits in social reward processing are differentially related to depression severity in the two disorders. PMID:27295401

Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL) Reveals the Sequential Differentiation of Sieve Element-Like Cells.

PubMed

Kondo, Yuki; Nurani, Alif Meem; Saito, Chieko; Ichihashi, Yasunori; Saito, Masato; Yamazaki, Kyoko; Mitsuda, Nobutaka; Ohme-Takagi, Masaru; Fukuda, Hiroo

2016-06-01

Cell differentiation is a complex process involving multiple steps, from initial cell fate specification to final differentiation. Procambial/cambial cells, which act as vascular stem cells, differentiate into both xylem and phloem cells during vascular development. Recent studies have identified regulatory cascades for xylem differentiation. However, the molecular mechanism underlying phloem differentiation is largely unexplored due to technical challenges. Here, we established an ectopic induction system for phloem differentiation named Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL). Our results verified similarities between VISUAL-induced Arabidopsis thaliana phloem cells and in vivo sieve elements. We performed network analysis using transcriptome data with VISUAL to dissect the processes underlying phloem differentiation, eventually identifying a factor involved in the regulation of the master transcription factor gene APL Thus, our culture system opens up new avenues not only for genetic studies of phloem differentiation, but also for future investigations of multidirectional differentiation from vascular stem cells. © 2016 American Society of Plant Biologists. All rights reserved.

Language experience differentiates prefrontal and subcortical activation of the cognitive control network in novel word learning

PubMed Central

King, Kelly E.; Hernandez, Arturo E.

2012-01-01

The purpose of this study was to examine the cognitive control mechanisms in adult English speaking monolinguals compared to early sequential Spanish-English bilinguals during the initial stages of novel word learning. Functional magnetic resonance imaging during a lexico-semantic task after only two hours of exposure to novel German vocabulary flashcards showed that monolinguals activated a broader set of cortical control regions associated with higher-level cognitive processes, including the supplementary motor area (SMA), anterior cingulate (ACC), and dorsolateral prefrontal cortex (DLPFC), as well as the caudate, implicated in cognitive control of language. However, bilinguals recruited a more localized subcortical network that included the putamen, associated more with motor control of language. These results suggest that experience managing multiple languages may differentiate the learning strategy and subsequent neural mechanisms of cognitive control used by bilinguals compared to monolinguals in the early stages of novel word learning. PMID:23194816

Isotopic And Geochemical Investigations Of Meteorites

NASA Technical Reports Server (NTRS)

Walker, Richard J.

2005-01-01

The primary goals of our research over the past four years are to constrain the timing of certain early planetary accretion/differentiation events, and to constrain the proportions and provenance of materials involved in these processes. This work was achieved via the analysis and interpretation of long- and short-lived isotope systems, and the study of certain trace elements. Our research targeted these goals primarily via the application of the Re-187, Os-187, Pt-190 Os-186 Tc-98 Ru-99 and Tc-99 Ru-99 isotopic systems, and the determination/modeling of abundances of the highly siderophile elements (HSE; including Re, Os, Ir, Ru, Pd, Pt, and maybe Tc). The specific events we examined include the segregation and crystallization histories of asteroidal cores, the accretion and metamorphic histories of chondrites and chondrite components, and the accretionary and differentiation histories of Mars and the Moon.

UVA and UVB Irradiation Differentially Regulate microRNA Expression in Human Primary Keratinocytes

PubMed Central

Kraemer, Anne; Chen, I-Peng; Henning, Stefan; Faust, Alexandra; Volkmer, Beate; Atkinson, Michael J.; Moertl, Simone; Greinert, Ruediger

2013-01-01

MicroRNA (miRNA)-mediated regulation of the cellular transcriptome is an important epigenetic mechanism for fine-tuning regulatory pathways. These include processes related to skin cancer development, progression and metastasis. However, little is known about the role of microRNA as an intermediary in the carcinogenic processes following exposure to UV-radiation. We now show that UV irradiation of human primary keratinocytes modulates the expression of several cellular miRNAs. A common set of miRNAs was influenced by exposure to both UVA and UVB. However, each wavelength band also activated a distinct subset of miRNAs. Common sets of UVA- and UVB-regulated miRNAs harbor the regulatory elements GLYCA-nTRE, GATA-1-undefined-site-13 or Hox-2.3-undefined-site-2 in their promoters. In silico analysis indicates that the differentially expressed miRNAs responding to UV have potential functions in the cellular pathways of cell growth and proliferation. Interestingly, the expression of miR-23b, which is a differentiation marker of human keratinocytes, is remarkably up-regulated after UVA irradiation. Studying the interaction between miR-23b and its putative skin-relevant targets using a Luciferase reporter assay revealed that RRAS2 (related RAS viral oncogene homolog 2), which is strongly expressed in highly aggressive malignant skin cancer, to be a direct target of miR-23b. This study demonstrates for the first time a differential miRNA response to UVA and UVB in human primary keratinocytes. This suggests that selective regulation of signaling pathways occurs in response to different UV energies. This may shed new light on miRNA-regulated carcinogenic processes involved in UV-induced skin carcinogenesis. PMID:24391759

Quantitative Dynamics of Proteome, Acetylome, and Succinylome during Stem-Cell Differentiation into Hepatocyte-like Cells.

PubMed

Liu, Zekun; Zhang, Qing-Bin; Bu, Chen; Wang, Dawei; Yu, Kai; Gan, Zhixue; Chang, Jianfeng; Cheng, Zhongyi; Liu, Zexian

2018-06-21

Stem-cell differentiation is a complex biological process controlled by a series of functional protein clusters and signaling transductions, especially metabolism-related pathways. Although previous studies have quantified the proteome and phosphoproteome for stem-cell differentiation, the investigation of acylation-mediated regulation is still absent. In this study, we quantitatively profiled the proteome, acetylome, and succinylome in pluripotent human embryonic stem cells (hESCs) and differentiated hepatocyte-like cells (HLCs). In total, 3843 proteins, 185 acetylation sites in 103 proteins, and 602 succinylation sites in 391 proteins were quantified. The quantitative proteome showed that in differentiated HLCs the TGF-β, JAK-STAT, and RAS signaling pathways were activated, whereas ECM-related processes such as sulfates and leucine degradation were depressed. Interestingly, it was observed that the acetylation and succinylation were more intensive in hESCs, whereas protein processing in endoplasmic reticulum and the carbon metabolic pathways were especially highly succinylated. Because the metabolism patterns in pluripotent hESCs and the differentiated HLCs were different, we proposed that the dynamic acylations, especially succinylation, might regulate the Warburg-like effect and TCA cycle during differentiation. Taken together, we systematically profiled the protein and acylation levels of regulation in pluripotent hESCs and differentiated HLCs, and the results indicated the important roles of acylation in pluripotency maintenance and differentiation.

Geochemical processes controlling water salinization in an irrigated basin in Spain: identification of natural and anthropogenic influence.

PubMed

Merchán, D; Auqué, L F; Acero, P; Gimeno, M J; Causapé, J

2015-01-01

Salinization of water bodies represents a significant risk in water systems. The salinization of waters in a small irrigated hydrological basin is studied herein through an integrated hydrogeochemical study including multivariate statistical analyses and geochemical modeling. The study zone has two well differentiated geologic materials: (i) Quaternary sediments of low salinity and high permeability and (ii) Tertiary sediments of high salinity and very low permeability. In this work, soil samples were collected and leaching experiments conducted on them in the laboratory. In addition, water samples were collected from precipitation, irrigation, groundwater, spring and surface waters. The waters show an increase in salinity from precipitation and irrigation water to ground- and, finally, surface water. The enrichment in salinity is related to the dissolution of soluble mineral present mainly in the Tertiary materials. Cation exchange, precipitation of calcite and, probably, incongruent dissolution of dolomite, have been inferred from the hydrochemical data set. Multivariate statistical analysis provided information about the structure of the data, differentiating the group of surface waters from the groundwaters and the salinization from the nitrate pollution processes. The available information was included in geochemical models in which hypothesis of consistency and thermodynamic feasibility were checked. The assessment of the collected information pointed to a natural control on salinization processes in the Lerma Basin with minimal influence of anthropogenic factors. Copyright © 2014 Elsevier B.V. All rights reserved.

Transcription activation by NtcA and 2-oxoglutarate of three genes involved in heterocyst differentiation in the cyanobacterium Anabaena sp. strain PCC 7120.

PubMed

Valladares, Ana; Flores, Enrique; Herrero, Antonia

2008-09-01

In Anabaena sp. strain PCC 7120, differentiation of heterocysts takes place in response to the external cue of combined nitrogen deprivation, allowing the organism to fix atmospheric nitrogen in oxic environments. NtcA, a global transcriptional regulator of cyanobacteria, is required for activation of the expression of multiple genes involved in heterocyst differentiation, including key regulators that are specific to the process. We have set up a fully defined in vitro system, which includes the purified Anabaena RNA polymerase, and have studied the effects of NtcA and its signaling effector 2-oxoglutarate on RNA polymerase binding, open complex formation, and transcript production from promoters of the hetC, nrrA, and devB genes that are activated by NtcA at different stages of heterocyst differentiation. Both RNA polymerase and NtcA could specifically bind to the target DNA in the absence of any effector. 2-Oxoglutarate had a moderate positive effect on NtcA binding, and NtcA had a limited positive effect on RNA polymerase recruitment at the promoters. However, a stringent requirement of both NtcA and 2-oxoglutarate was observed for the detection of open complexes and transcript production at the three investigated promoters. These results support a key role for 2-oxoglutarate in transcription activation in the developing heterocyst.

Dynamic transcription profiles of “Qinguan” apple (Malus × domestica) leaves in response to Marssonina coronaria inoculation

PubMed Central

Xu, Jianhua; Li, Miaomiao; Jiao, Peng; Tao, Hongxia; Wei, Ningning; Ma, Fengwang; Zhang, Junke

2015-01-01

Marssonina apple blotch, caused by the fungus Marssonina coronaria, is one of the most destructive apple diseases in China and East Asia. A better understanding of the plant's response to fungi during pathogenesis is urgently needed to improve plant resistance and to breed resistant cultivars. To address this, the transcriptomes of “Qinguan” (a cultivar with high resistance to M. coronaria) apple leaves were sequenced at 12, 24, 48, and 72 h post-inoculation (hpi) with Marssonina coronaria. The comparative results showed that a total of 1956 genes were differentially expressed between the inoculated and control samples at the 4 time points. Gene ontology (GO) term enrichment analysis of differentially expressed genes (DEGs) revealed changes in cellular component, secondary metabolism including chalcone isomerase activity, phytoalexin biosynthetic process, anthocyanin-containing compound biosynthetic process, lignin biosynthetic process, positive regulation of flavonoid biosynthetic process; and molecular functions or biological processes related to the defense response, biotic stimulus response, wounding response and fungus response. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that DEGs were significantly enriched in flavonoid biosynthesis, vitamin B6 metabolism, phenylpropanoid biosynthesis, and the stilbenoid, diarylheptanoid and gingerol biosynthesis pathways. Furthermore, the importance of changes in cellular components and partial polyphenol compounds when encountering M. coronaria are discussed. PMID:26528306

Advances on microRNA in regulating mammalian skeletal muscle development.

PubMed

Li, Xin-Yun; Fu, Liang-Liang; Cheng, Hui-Jun; Zhao, Shu-Hong

2017-11-20

MicroRNA (miRNA) is a class of short non-coding RNA, which is about 22 bp in length. In mammals, miRNA exerts its funtion through binding with the 3°-UTR region of target genes and inhibiting their translation. Skeletal muscle development is a complex event, including: proliferation, migration and differentiation of skeletal muscle stem cells; proliferation, differentiation and fusion of myocytes; as well as hypertrophy, energy metabolism and conversion of muscle fiber types. The miRNA plays important roles in all processes of skeletal muscle development through targeting the key factors of different stages. Herein we summarize the miRNA related to muscle development, providing a better understanding of the skeletal muscle development.

Simulation of complex pharmacokinetic models in Microsoft Excel.

PubMed

Meineke, Ingolf; Brockmöller, Jürgen

2007-12-01

With the arrival of powerful personal computers in the office numerical methods are accessible to everybody. Simulation of complex processes therefore has become an indispensible tool in research and education. In this paper Microsoft EXCEL is used as a platform for a universal differential equation solver. The software is designed as an add-in aiming at a minimum of required user input to perform a given task. Four examples are included to demonstrate both, the simplicity of use and the versatility of possible applications. While the layout of the program is admittedly geared to the needs of pharmacokineticists, it can be used in any field where sets of differential equations are involved. The software package is available upon request.

Micron-Scale Differential Scanning Calorimeter on a Chip

DOEpatents

Cavicchi, Richard E; Poirier, Gregory Ernest; Suehle, John S; Gaitan, Michael; Tea, Nim H

1998-06-30

A differential scanning microcalorimeter produced on a silicon chip enables microscopic scanning calorimetry measurements of small samples and thin films. The chip may be fabricated using standard CMOS processes. The microcalorimeter includes a reference zone and a sample zone. The reference and sample zones may be at opposite ends of a suspended platform or may reside on separate platforms. An integrated polysilicon heater provides heat to each zone. A thermopile consisting of a succession of thermocouple junctions generates a voltage representing the temperature difference between the reference and sample zones. Temperature differences between the zones provide information about the chemical reactions and phase transitions that occur in a sample placed in the sample zone.

Second Order Born Effects in the Perpendicular Plane Ionization of Xe (5p) Atoms

NASA Astrophysics Data System (ADS)

Purohit, G.; Singh, Prithvi; Patidar, Vinod

We report triple differential cross section (TDCS) results for the perpendicular plane ionization of xenon atoms at incident electron energies 5, 10, 20, 30, and 40 eV above ionization potential. The TDCS calculation have been preformed within the modified distorted wave Born approximation formalism including the second order Born (SBA) amplitude. We compare the (e, 2e) TDCS result of our calculation with the very recent measurements of Nixon and Murray [Phys. Rev. A 85, 022716 (2012)] and relativistic DWBA-G results of Illarionov and Stauffer [J. Phys. B: At. Mol. Opt. Phys. 45, 225202 (2012)] and discuss the process contributing to structure seen in the differential cross section.

Integrated Kerr comb-based reconfigurable transversal differentiator for microwave photonic signal processing

NASA Astrophysics Data System (ADS)

Xu, Xingyuan; Wu, Jiayang; Shoeiby, Mehrdad; Nguyen, Thach G.; Chu, Sai T.; Little, Brent E.; Morandotti, Roberto; Mitchell, Arnan; Moss, David J.

2018-01-01

An arbitrary-order intensity differentiator for high-order microwave signal differentiation is proposed and experimentally demonstrated on a versatile transversal microwave photonic signal processing platform based on integrated Kerr combs. With a CMOS-compatible nonlinear micro-ring resonator, high quality Kerr combs with broad bandwidth and large frequency spacings are generated, enabling a larger number of taps and an increased Nyquist zone. By programming and shaping individual comb lines' power, calculated tap weights are realized, thus achieving a versatile microwave photonic signal processing platform. Arbitrary-order intensity differentiation is demonstrated on the platform. The RF responses are experimentally characterized, and systems demonstrations for Gaussian input signals are also performed.

Markers of Developmentally Regulated Programmed Cell Death and Their Analysis in Cereal Seeds.

PubMed

Domínguez, Fernando; Cejudo, Francisco Javier

2018-01-01

Programmed cell death (PCD) is a key process for the development and differentiation of multicellular organisms, which is characterized by well-defined morphological and biochemical features. These include chromatin condensation, DNA degradation and nuclear fragmentation, with nucleases and proteases playing a relevant function in these processes. In this chapter we describe methods routinely used for the analysis of hallmarks of developmentally regulated PCD in cereal seed tissues, which are based on agarose and polyacrylamide gel electrophoresis, in situ staining of DNA fragmentation, and cell-free assays of relevant enzymatic activities.

Alternative mRNA polyadenylation in eukaryotes: an effective regulator of gene expression

PubMed Central

Lutz, Carol S.; Moreira, Alexandra

2010-01-01

Alternative RNA processing mechanisms, including alternative splicing and alternative polyadenylation, are increasingly recognized as important regulators of gene expression. This article will focus on what has recently been described about alternative polyadenylation in development, differentiation, and disease in higher eukaryotes. We will also describe how the evolving global methodologies for examining the cellular transcriptome, both experimental and bioinformatic, are revealing new details about the complex nature of alternative 3′ end formation, as well as interactions with other RNA-mediated and RNA processing mechanisms. PMID:21278855

Recent Results From MINERvA

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

Patrick, Cheryl

The MINERvA detector is situated in Fermilab's NuMI beam, which provides neutrinos and antineutrinos in the 1-20 GeV range. It is designed to make precision cross-section measurements for scattering processes on various nuclei. These proceedings summarize the differential cross-section distributions measured for several different processes. Comparison of these with various models hints at additional nuclear effects not included in common simulations. These results will help constrain generators' nuclear models and reduce systematic uncertainties on their predictions. An accurate cross-section model, with minimal uncertainties, is vital to oscillation experiments.

Differential geometry-based solvation and electrolyte transport models for biomolecular modeling: a review

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

Wei, Guowei; Baker, Nathan A.

2016-11-11

This chapter reviews the differential geometry-based solvation and electrolyte transport for biomolecular solvation that have been developed over the past decade. A key component of these methods is the differential geometry of surfaces theory, as applied to the solvent-solute boundary. In these approaches, the solvent-solute boundary is determined by a variational principle that determines the major physical observables of interest, for example, biomolecular surface area, enclosed volume, electrostatic potential, ion density, electron density, etc. Recently, differential geometry theory has been used to define the surfaces that separate the microscopic (solute) domains for biomolecules from the macroscopic (solvent) domains. In thesemore » approaches, the microscopic domains are modeled with atomistic or quantum mechanical descriptions, while continuum mechanics models (including fluid mechanics, elastic mechanics, and continuum electrostatics) are applied to the macroscopic domains. This multiphysics description is integrated through an energy functional formalism and the resulting Euler-Lagrange equation is employed to derive a variety of governing partial differential equations for different solvation and transport processes; e.g., the Laplace-Beltrami equation for the solvent-solute interface, Poisson or Poisson-Boltzmann equations for electrostatic potentials, the Nernst-Planck equation for ion densities, and the Kohn-Sham equation for solute electron density. Extensive validation of these models has been carried out over hundreds of molecules, including proteins and ion channels, and the experimental data have been compared in terms of solvation energies, voltage-current curves, and density distributions. We also propose a new quantum model for electrolyte transport.« less

Genetic and molecular control of Osterix in skeletal formation

PubMed Central

Sinha, Krishna M.; Zhou, Xin

2013-01-01

Osteoblast differentiation is a multi-step process where mesenchymal cells differentiate into osteoblast lineage cells including osteocytes. Osterix (Osx) is an osteoblast-specific transcription factor which activates a repertoire of genes during differentiation of preosteoblasts into mature osteoblasts and osteocytes. The essential role of Osx in the genetic program of bone formation and in bone homeostasis is well established. Osx mutant embryos do not form bone and fail to express osteoblast-specific marker genes. Inactivation of Osx in mice after birth causes multiple skeletal phenotypes including lack of new bone formation, absence of resorption of mineralized cartilage, and defects in osteocyte maturation and function. Since Osx is a major effector in skeletal formation, studies on Osx gained momentum over the last five-seven years and implicated its important function in tooth formation as well as in healing of bone fractures. This review outlines mouse genetic studies that establish the essential role of Osx in bone and tooth formation as well as in healing of bone fractures. We also discuss the recent advances in regulation of Osx expression which is under control of a transcriptional network, signaling pathways, and epigenetic regulation. Finally we summarize important findings on the positive and negative regulation of Osx’s transcriptional activity through protein-protein interactions in expression of its target genes during osteoblast differentiation. In particular, the identification of the histone demethylase NO66 as an Osx-interacting protein which negatively regulates Osx activity opens further avenues in studying epigenetic control of Osx target genes during differentiation and maturation of osteoblasts. PMID:23225263

Activation of the PI3K/Akt pathway by oxidative stress mediates high glucose-induced increase of adipogenic differentiation in primary rat osteoblasts.

PubMed

Zhang, Yu; Yang, Jian-Hong

2013-11-01

Diabetes mellitus is associated with increased risk of osteopenia and bone fracture that may be related to hyperglycemia. However, the mechanisms accounting for diabetic bone disorder are unclear. Here, we showed that high glucose significantly promoted the production of reactive oxygen species (ROS) in rat primary osteoblasts. Most importantly, we reported for the first time that ROS induced by high glucose increased alkaline phosphatase activity, inhibited type I collagen (collagen I) protein level and cell mineralization, as well as gene expression of osteogenic markers including runt-related transcription factor 2 (Runx2), collagen I, and osteocalcin, but promoted lipid droplet formation and gene expression of adipogenic markers including peroxisome proliferator-activated receptor gamma, adipocyte fatty acid binding protein (aP2), and adipsin, which were restored by pretreatment with N-acetyl-L-cysteine (NAC), a ROS scavenger. Moreover, high glucose-induced oxidative stress activated PI3K/Akt pathway to inhibited osteogenic differentiation but stimulated adipogenic differentiation. In contrast, NAC and a PI3K inhibitor, LY-294002, reversed the down-regulation of osteogenic markers and the up-regulation of adipogenic markers as well as the activation of Akt under high glucose. These results indicated that oxidative stress played a key role in high glucose-induced increase of adipogenic differentiation, which contributed to the inhibition of osteogenic differentiation. This process was mediated by PI3K/Akt pathway in rat primary osteoblasts. Hence, suppression of oxidative stress could be a potential therapeutic approach for diabetic osteopenia. © 2013 Wiley Periodicals, Inc.

Current applications of human pluripotent stem cells: possibilities and challenges.

PubMed

Ho, Pai-Jiun; Yen, Men-Luh; Yet, Shaw-Fang; Yen, B Linju

2012-01-01

Stem cells are self-renewable cells with the differentiation capacity to develop into somatic cells with biological functions. This ability to sustain a renewable source of multi- and/or pluripotential differentiation has brought new hope to the field of regenerative medicine in terms of cell therapy and tissue engineering. Moreover, stem cells are invaluable tools as in vitro models for studying diverse fields, from basic scientific questions such as developmental processes and lineage commitment, to practical application including drug screening and testing. The stem cells with widest differentiation potential are pluripotent stem cells (PSCs), which are rare cells with the ability to generate somatic cells from all three germ layers. PSCs are considered the most optimal choice for therapeutic potential of stem cells, bringing new impetus to the field of regenerative medicine. In this article, we discuss the therapeutic potential of human PSCs (hPSCs) including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), reviewing the current preclinical and clinical data using these stem cells. We describe the classification of different sources of hPSCs, ongoing research, and currently encountered clinical obstacles of these novel and versatile human stem cells.

Electrodermal responses during appetitive conditioning are sensitive to contingency instruction ambiguity.

PubMed

van den Akker, Karolien; Nederkoorn, Chantal; Jansen, Anita

2017-08-01

Studies on human appetitive conditioning using food rewards can benefit from including psychophysiological outcome measures. The present study tested whether the skin conductance response can function as a measure of differential responding in an appetitive conditioning paradigm including an acquisition and extinction phase, and examined which time window during a trial is most sensitive to conditioning effects. As a secondary aim, the effects of ambiguous vs. non-ambiguous contingency instructions on conditioned responses (skin conductance responses, US expectancies, chocolate desires, and CS evaluations) were assessed. Results indicated differential skin conductance responses in an anticipatory time window and during unexpected omission of the US in early extinction. Interestingly however, anticipatory responses were only found for participants who received ambiguous contingency instructions - possibly indicating a call for additional processing resources in response to the ambiguous CS+. Further, ambiguous instructions slowed the extinction of US expectancies but did not influence chocolate desires and CS evaluations. It is concluded that skin conductance can function as a sensitive measure of differential responding in appetitive conditioning, though its sensitivity might depend on the specific task context. Copyright © 2017 Elsevier B.V. All rights reserved.

Lens fibre cell differentiation and organelle loss: many paths lead to clarity

PubMed Central

Wride, Michael A.

2011-01-01

The programmed removal of organelles from differentiating lens fibre cells contributes towards lens transparency through formation of an organelle-free zone (OFZ). Disruptions in OFZ formation are accompanied by the persistence of organelles in lens fibre cells and can contribute towards cataract. A great deal of work has gone into elucidating the nature of the mechanisms and signalling pathways involved. It is apparent that multiple, parallel and redundant pathways are involved in this process and that these pathways form interacting networks. Furthermore, it is possible that the pathways can functionally compensate for each other, for example in mouse knockout studies. This makes sense given the importance of lens clarity in an evolutionary context. Apoptosis signalling and proteolytic pathways have been implicated in both lens fibre cell differentiation and organelle loss, including the Bcl-2 and inhibitor of apoptosis families, tumour necrosis factors, p53 and its regulators (such as Mdm2) and proteolytic enzymes, including caspases, cathepsins, calpains and the ubiquitin–proteasome pathway. Ongoing approaches being used to dissect the molecular pathways involved, such as transgenics, lens-specific gene deletion and zebrafish mutants, are discussed here. Finally, some of the remaining unresolved issues and potential areas for future studies are highlighted. PMID:21402582

The genetic network controlling plasma cell differentiation.

PubMed

Nutt, Stephen L; Taubenheim, Nadine; Hasbold, Jhagvaral; Corcoran, Lynn M; Hodgkin, Philip D

2011-10-01

Upon activation by antigen, mature B cells undergo immunoglobulin class switch recombination and differentiate into antibody-secreting plasma cells, the endpoint of the B cell developmental lineage. Careful quantitation of these processes, which are stochastic, independent and strongly linked to the division history of the cell, has revealed that populations of B cells behave in a highly predictable manner. Considerable progress has also been made in the last few years in understanding the gene regulatory network that controls the B cell to plasma cell transition. The mutually exclusive transcriptomes of B cells and plasma cells are maintained by the antagonistic influences of two groups of transcription factors, those that maintain the B cell program, including Pax5, Bach2 and Bcl6, and those that promote and facilitate plasma cell differentiation, notably Irf4, Blimp1 and Xbp1. In this review, we discuss progress in the definition of both the transcriptional and cellular events occurring during late B cell differentiation, as integrating these two approaches is crucial to defining a regulatory network that faithfully reflects the stochastic features and complexity of the humoral immune response. 2011 Elsevier Ltd. All rights reserved.

Vinpocetine Attenuates the Osteoblastic Differentiation of Vascular Smooth Muscle Cells

PubMed Central

Chen, Xiu-Juan; Wang, Na; Yi, Peng-Fei; Song, Min; Zhang, Bo; Wang, Yu-Zhong; Liang, Qiu-Hua

2016-01-01

Vascular calcification is an active process of osteoblastic differentiation of vascular smooth muscle cells; however, its definite mechanism remains unknown. Vinpocetine, a derivative of the alkaloid vincamine, has been demonstrated to inhibit the high glucose-induced proliferation of vascular smooth muscle cells; however, it remains unknown whether vinpocetine can affect the osteoblastic differentiation of vascular smooth muscle cells. We hereby investigated the effect of vinpocetine on vascular calcification using a beta-glycerophosphate-induced cell model. Our results showed that vinpocetine significantly reduced the osteoblast-like phenotypes of vascular smooth muscle cells including ALP activity, osteocalcin, collagen type I, Runx2 and BMP-2 expression as well as the formation of mineralized nodule. Vinpocetine, binding to translocation protein, induced phosphorylation of extracellular signal-related kinase and Akt and thus inhibited the translocation of nuclear factor-kappa B into the nucleus. Silencing of translocator protein significantly attenuated the inhibitory effect of vinpocetine on osteoblastic differentiation of vascular smooth muscle cells. Taken together, vinpocetine may be a promising candidate for the clinical therapy of vascular calcification. PMID:27589055

Expression of different functional isoforms in haematopoiesis.

PubMed

Grech, Godfrey; Pollacco, Joel; Portelli, Mark; Sacco, Keith; Baldacchino, Shawn; Grixti, Justine; Saliba, Christian

2014-01-01

Haematopoiesis is a complex process regulated at various levels facilitating rapid responses to external factors including stress, modulation of lineage commitment and terminal differentiation of progenitors. Although the transcription program determines the RNA pool of a cell, various mRNA strands can be obtained from the same template, giving rise to multiple protein isoforms. The majority of variants and isoforms co-occur in normal haematopoietic cells or are differentially expressed at various maturity stages of progenitor maturation and cellular differentiation within the same lineage or across lineages. Genetic aberrations or specific cellular states result in the predominant expression of abnormal isoforms leading to deregulation and disease. The presence of upstream open reading frames (uORF) in 5' untranslated regions (UTRs) of a transcript, couples the utilization of start codons with the cellular status and availability of translation initiation factors (eIFs). In addition, tissue-specific and cell lineage-specific alternative promoter use, regulates several transcription factors producing transcript variants with variable 5' exons. In this review, we propose to give a detailed account of the differential isoform formation, causing haematological malignancies.

miR-96 promotes osteogenic differentiation by suppressing HBEGF-EGFR signaling in osteoblastic cells.

PubMed

Yang, Mingfu; Pan, Yong; Zhou, Yue

2014-12-20

MicroRNAs (miRNAs) are a class of small non-coding RNAs with important roles in various biological and pathological processes, including osteoblast differentiation. Here, we identified miR-96 as a positive regulator of osteogenic differentiation in a mouse osteoblastic cell line (MC3T3-E1) and in mouse bone marrow-derived mesenchymal stem cells. Moreover, we found that miR-96 down-regulates post-transcriptional expression of heparin-binding EGF-like growth factor (HB-EGF) by specifically binding to the 3'untranslated region of HB-EGF mRNA. Furthermore, in MC3T3-E1 cells, miR-96-induced HB-EGF down-regulation suppressed the phosphorylation of epidermal growth factor receptor (EGFR) and of extracellular signal-regulated kinase 1 (ERK1) and AKT, which both lie downstream of EGFR activation. Taken together, miR-96 promotes osteogenic differentiation by inhibiting HB-EGF and by blocking the HB-EGF-EGFR signaling pathway in osteoblastic cells. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

T cell exit from quiescence and differentiation into Th2 cells depend on Raptor-mTORC1-mediated metabolic programming

PubMed Central

Yang, Kai; Shrestha, Sharad; Zeng, Hu; Karmaus, Peer W.F.; Neale, Geoffrey; Vogel, Peter; Guertin, David A.; Lamb, Richard F.; Chi, Hongbo

2014-01-01

SUMMARY Naïve T cells respond to antigen stimulation by exiting from quiescence and initiating clonal expansion and functional differentiation, but the control mechanism is elusive. Here we describe that Raptor-mTORC1-dependent metabolic programming is a central determinant of this transitional process. Loss of Raptor abrogated T cell priming and Th2 cell differentiation, although Raptor function is less important for continuous proliferation of actively cycling cells. mTORC1 coordinated multiple metabolic programs in T cells including glycolysis, lipid synthesis and oxidative phosphorylation to mediate antigen-triggered exit from quiescence. mTORC1 further linked glucose metabolism to the initiation of Th2 cell differentiation by orchestrating cytokine receptor expression and cytokine responsiveness. Activation of Raptor-mTORC1 integrated T cell receptor and CD28 co-stimulatory signals in antigen-stimulated T cells. Our studies identify a Raptor-mTORC1-dependent pathway linking signal-dependent metabolic reprogramming to quiescence exit, and this in turn coordinates lymphocyte activation and fate decisions in adaptive immunity. PMID:24315998

Differentiation of the asteroid Ceres as revealed by its shape.

PubMed

Thomas, P C; Parker, J Wm; McFadden, L A; Russell, C T; Stern, S A; Sykes, M V; Young, E F

2005-09-08

The accretion of bodies in the asteroid belt was halted nearly 4.6 billion years ago by the gravitational influence of the newly formed giant planet Jupiter. The asteroid belt therefore preserves a record of both this earliest epoch of Solar System formation and variation of conditions within the solar nebula. Spectral features in reflected sunlight indicate that some asteroids have experienced sufficient thermal evolution to differentiate into layered structures. The second most massive asteroid--4 Vesta--has differentiated to a crust, mantle and core. 1 Ceres, the largest and most massive asteroid, has in contrast been presumed to be homogeneous, in part because of its low density, low albedo and relatively featureless visible reflectance spectrum, similar to carbonaceous meteorites that have suffered minimal thermal processing. Here we show that Ceres has a shape and smoothness indicative of a gravitationally relaxed object. Its shape is significantly less flattened than that expected for a homogeneous object, but is consistent with a central mass concentration indicative of differentiation. Possible interior configurations include water-ice-rich mantles over a rocky core.

Identification of transcription coactivator OCA-B-dependent genes involved in antigen-dependent B cell differentiation by cDNA array analyses.

PubMed

Kim, Unkyu; Siegel, Rachael; Ren, Xiaodi; Gunther, Cary S; Gaasterland, Terry; Roeder, Robert G

2003-07-22

The tissue-specific transcriptional coactivator OCA-B is required for antigen-dependent B cell differentiation events, including germinal center formation. However, the identity of OCA-B target genes involved in this process is unknown. This study has used large-scale cDNA arrays to monitor changes in gene expression patterns that accompany mature B cell differentiation. B cell receptor ligation alone induces many genes involved in B cell expansion, whereas B cell receptor and helper T cell costimulation induce genes associated with B cell effector function. OCA-B expression is induced by both B cell receptor ligation alone and helper T cell costimulation, suggesting that OCA-B is involved in B cell expansion as well as B cell function. Accordingly, several genes involved in cell proliferation and signaling, such as Lck, Kcnn4, Cdc37, cyclin D3, B4galt1, and Ms4a11, have been identified as OCA-B-dependent genes. Further studies on the roles played by these genes in B cells will contribute to an understanding of B cell differentiation.

Roles of autophagy in controlling stem cell identity: a perspective of self-renewal and differentiation.

PubMed

Sotthibundhu, Areechun; Promjuntuek, Wilasinee; Liu, Min; Shen, Sanbing; Noisa, Parinya

2018-04-25

Autophagy is crucial for the removal of dysfunctional organelles and protein aggregates and for maintaining stem cell homeostasis, which includes self-renewal, cell differentiation and somatic reprogramming. Loss of self-renewal capacity and pluripotency is a major obstacle to stem cell-based therapies. It has been reported that autophagy regulates stem cells under biological stimuli, starvation, hypoxia, generation of reactive oxygen species (ROS) and cellular senescence. On the one hand, autophagy is shown to play roles in self-renewal by co-function with the ubiquitin-proteasome system (UPS) to promote pluripotency-associated proteins (NANOG, OCT4 and SOX2) in human embryonic stem cells (hESCs). On the other hand, autophagy activity acts as cell reprogramming processes that play an important role for clearance fate determination and upregulates neural and cardiac differentiation. Deregulation of autophagy triggers protein disorders such as neurodegenerative cardiac/muscle diseases and cancer. Therefore, understanding of the roles of the autophagy in stem cell renewal and differentiation may benefit therapeutic development for a range of human diseases.

Informatics in radiology: radiology gamuts ontology: differential diagnosis for the Semantic Web.

PubMed

Budovec, Joseph J; Lam, Cesar A; Kahn, Charles E

2014-01-01

The Semantic Web is an effort to add semantics, or "meaning," to empower automated searching and processing of Web-based information. The overarching goal of the Semantic Web is to enable users to more easily find, share, and combine information. Critical to this vision are knowledge models called ontologies, which define a set of concepts and formalize the relations between them. Ontologies have been developed to manage and exploit the large and rapidly growing volume of information in biomedical domains. In diagnostic radiology, lists of differential diagnoses of imaging observations, called gamuts, provide an important source of knowledge. The Radiology Gamuts Ontology (RGO) is a formal knowledge model of differential diagnoses in radiology that includes 1674 differential diagnoses, 19,017 terms, and 52,976 links between terms. Its knowledge is used to provide an interactive, freely available online reference of radiology gamuts ( www.gamuts.net ). A Web service allows its content to be discovered and consumed by other information systems. The RGO integrates radiologic knowledge with other biomedical ontologies as part of the Semantic Web. © RSNA, 2014.

Alternative polyadenylation of mRNA precursors

PubMed Central

Tian, Bin; Manley, James L.

2017-01-01

Alternative polyadenylation (APA) is an RNA-processing mechanism that generates distinct 3′ termini on mRNAs and other RNA polymerase II transcripts. It is widespread across all eukaryotic species and is recognized as a major mechanism of gene regulation. APA exhibits tissue specificity and is important for cell proliferation and differentiation. In this Review, we discuss the roles of APA in diverse cellular processes, including mRNA metabolism, protein diversification and protein localization, and more generally in gene regulation. We also discuss the molecular mechanisms underlying APA, such as variation in the concentration of core processing factors and RNA-binding proteins, as well as transcription-based regulation. PMID:27677860

Helicopter flight test demonstration of differential GPS

NASA Technical Reports Server (NTRS)

Denaro, R. P.; Beser, J.

1985-01-01

An off-line post-mission processing facility is being established by NASA Ames Research Center to analyze differential GPS flight tests. The current and future differential systems are described, comprising an airborne segment in an SH-3 helicopter, a GPS ground reference station, and a tracking system. The post-mission processing system provides for extensive measurement analysis and differential computation. Both differential range residual corrections and navigation corrections are possible. Some preliminary flight tests were conducted in a landing approach scenario and statically. Initial findings indicate the possible need for filter matching between airborne and ground systems (if used in a navigation correction technique), the advisability of correction smoothing before airborne incorporation, and the insensitivity of accuracy to either of the differential techniques or to update rates.

Parallel Algorithm Solves Coupled Differential Equations

NASA Technical Reports Server (NTRS)

Hayashi, A.

1987-01-01

Numerical methods adapted to concurrent processing. Algorithm solves set of coupled partial differential equations by numerical integration. Adapted to run on hypercube computer, algorithm separates problem into smaller problems solved concurrently. Increase in computing speed with concurrent processing over that achievable with conventional sequential processing appreciable, especially for large problems.

Robust crop and weed segmentation under uncontrolled outdoor illumination.

PubMed

Jeon, Hong Y; Tian, Lei F; Zhu, Heping

2011-01-01

An image processing algorithm for detecting individual weeds was developed and evaluated. Weed detection processes included were normalized excessive green conversion, statistical threshold value estimation, adaptive image segmentation, median filter, morphological feature calculation and Artificial Neural Network (ANN). The developed algorithm was validated for its ability to identify and detect weeds and crop plants under uncontrolled outdoor illuminations. A machine vision implementing field robot captured field images under outdoor illuminations and the image processing algorithm automatically processed them without manual adjustment. The errors of the algorithm, when processing 666 field images, ranged from 2.1 to 2.9%. The ANN correctly detected 72.6% of crop plants from the identified plants, and considered the rest as weeds. However, the ANN identification rates for crop plants were improved up to 95.1% by addressing the error sources in the algorithm. The developed weed detection and image processing algorithm provides a novel method to identify plants against soil background under the uncontrolled outdoor illuminations, and to differentiate weeds from crop plants. Thus, the proposed new machine vision and processing algorithm may be useful for outdoor applications including plant specific direct applications (PSDA).

Constitutive Proteasomal Degradation of TWIST-1 in Epithelial Ovarian Cancer Stem Cells Impacts Differentiation and Metastatic Potential

PubMed Central

Yin, Gang; Alvero, Ayesha B.; Craveiro, Vinicius; Holmberg, Jennie C.; Fu, Han-Hsuan; Montagna, Michele K.; Yang, Yang; Chefetz-Menaker, Ilana; Nuti, Sudhakar; Rossi, Michael; Silasi, Dan-Arin; Rutherford, Thomas; Mor, Gil

2013-01-01

Epithelial-mesenchymal transition (EMT) is a critical process for embryogenesis but is abnormally activated during cancer metastasis and recurrence. This process enables epithelial cancer cells to acquire mobility and traits associated with stemness. It is unknown whether epithelial stem cells or epithelial cancer stem cells are able to undergo EMT, and what molecular mechanism regulates this process in these specific cell types. We found that Epithelial Ovarian Cancer Stem cells (EOC stem cells) are the source of metastatic progenitor cells through a differentiation process involving EMT and Mesenchymal-Epithelial Transition (MET). We demonstrate both in vivo and in vitro the differentiation of EOC stem cells into mesenchymal spheroid-forming cells (MSFCs) and their capacity to initiate an active carcinomatosis. Furthermore, we demonstrate that human EOC stem cells injected i.p in mice are able to form ovarian tumors, suggesting that the EOC stem cells have the ability to “home” to the ovaries and establish tumors. Most interestingly, we found that TWIST1 is constitutively degraded in EOC stem cells, and that the acquisition of TWIST1 requires additional signals that will trigger the differentiation process. These findings are relevant for understanding the differentiation and metastasis process in EOC stem cells. PMID:22349827

Coding and non-coding gene regulatory networks underlie the immune response in liver cirrhosis.

PubMed

Gao, Bo; Zhang, Xueming; Huang, Yongming; Yang, Zhengpeng; Zhang, Yuguo; Zhang, Weihui; Gao, Zu-Hua; Xue, Dongbo

2017-01-01

Liver cirrhosis is recognized as being the consequence of immune-mediated hepatocyte damage and repair processes. However, the regulation of these immune responses underlying liver cirrhosis has not been elucidated. In this study, we used GEO datasets and bioinformatics methods to established coding and non-coding gene regulatory networks including transcription factor-/lncRNA-microRNA-mRNA, and competing endogenous RNA interaction networks. Our results identified 2224 mRNAs, 70 lncRNAs and 46 microRNAs were differentially expressed in liver cirrhosis. The transcription factor -/lncRNA- microRNA-mRNA network we uncovered that results in immune-mediated liver cirrhosis is comprised of 5 core microRNAs (e.g., miR-203; miR-219-5p), 3 transcription factors (i.e., FOXP3, ETS1 and FOS) and 7 lncRNAs (e.g., ENTS00000671336, ENST00000575137). The competing endogenous RNA interaction network we identified includes a complex immune response regulatory subnetwork that controls the entire liver cirrhosis network. Additionally, we found 10 overlapping GO terms shared by both liver cirrhosis and hepatocellular carcinoma including "immune response" as well. Interestingly, the overlapping differentially expressed genes in liver cirrhosis and hepatocellular carcinoma were enriched in immune response-related functional terms. In summary, a complex gene regulatory network underlying immune response processes may play an important role in the development and progression of liver cirrhosis, and its development into hepatocellular carcinoma.

Genomewide analysis indicates that queen larvae have lower methylation levels in the honey bee ( Apis mellifera)

NASA Astrophysics Data System (ADS)

Shi, Yuan Yuan; Yan, Wei Yu; Huang, Zachary Y.; Wang, Zi Long; Wu, Xiao Bo; Zeng, Zhi Jiang

2013-02-01

The honey bee is a social insect characterized by caste differentiation, by which a young larva can develop into either a queen or a worker. Despite possessing the same genome, queen and workers display marked differences in reproductive capacity, physiology, and behavior. Recent studies have shown that DNA methylation plays important roles in caste differentiation. To further explore the roles of DNA methylation in this process, we analyzed DNA methylome profiles of both queen larvae (QL) and worker larvae (WL) of different ages (2, 4, and 6 day old), by using methylated DNA immunoprecipitation-sequencing (meDIP-seq) technique. The global DNA methylation levels varied between the larvae of two castes. DNA methylation increased from 2-day- to 4-day-old QL and then decreased in 6-day-old larvae. In WL, methylation levels increased with age. The methylcytosines in both larvae were enriched in introns, followed by coding sequence (CDS) regions, CpG islands, 2 kbp downstream and upstream of genes, and 5' and 3' untranslated regions (UTRs). The number of differentially methylated genes (DMGs) in 2-, 4-, and 6-day-old QL and WL was 725, 3,013, and 5,049, respectively. Compared to 4- and 6-day-old WL, a large number of genes in QL were downmethylated, which were involved in many processes including development, reproduction, and metabolic regulation. In addition, some DMGs were concerned with caste differentiation.

Long-lasting and sex-specific consequences of elevated egg yolk testosterone for social behavior in Japanese quail.

PubMed

Schweitzer, Cécile; Goldstein, Michael H; Place, Ned J; Adkins-Regan, Elizabeth

2013-01-01

In birds, early exposure to steroid hormones deposited in egg yolks is hypothesized to result in long-lasting effects on brain and behavior. However, the long-term effects of maternal androgens on the development of social behavior, and whether these could interfere with the effects of the endogenous gonadal hormones that mediate sexual differentiation, remain poorly known. To answer these questions, we enhanced yolk testosterone by injecting testosterone (T) in oil into Japanese quail (Coturnix japonica) eggs prior to incubation. Vehicle-injected (V) eggs served as controls. From age 3 weeks to 8 weeks, sexual development was measured using morphological and physiological traits, and social behavior was measured, including male-typical sexual behavior. In females, treatment with testosterone boosted growth. Males from T-injected eggs developed an affiliative preference for familiar females and differed from V-injected males in the acoustic features of their crows, whereas sexual interest (looking behavior) and copulatory behavior were not affected. These long-lasting and sex-specific yolk testosterone effects on the development of dimorphic traits, but without disrupting sexual differentiation of reproductive behavior suggest potential organizational effects of maternal testosterone, but acting through separate processes than the endocrine mechanisms previously shown to control sexual differentiation. Separate processes could reflect the action of androgens at different times or on multiple targets that are differentially sensitive to steroids or develop at different rates. Copyright © 2012 Elsevier Inc. All rights reserved.

Characterization of visceral and subcutaneous adipose tissue transcriptome in pregnant women with and without spontaneous labor at term: Implication of alternative splicing in the metabolic adaptations of adipose tissue to parturition

PubMed Central

Mazaki-Tovi, Shali; Tarca, Adi L.; Vaisbuch, Edi; Kusanovic, Juan Pedro; Than, Nandor Gabor; Chaiworapongsa, Tinnakorn; Dong, Zhong; Hassan, Sonia S; Romero, Roberto

2018-01-01

OBJECTIVE The aim of this study was to determine gene expression and splicing changes associated with parturition and regions (visceral vs subcutaneous) of the adipose tissue of pregnant women. STUDY DESIGN The transcriptome of visceral and abdominal subcutaneous adipose tissue from pregnant women at term with (n=15) and without (n=25) spontaneous labor was profiled with Affymetrix GeneChip Human Exon 1.0 ST array. Overall gene expression changes and differential exon usage rate were compared between patient groups and adipose tissue regions (paired analyses). Selected genes were tested by quantitative reverse transcription–polymerase chain reaction. RESULTS Four hundred eighty-two genes were differentially expressed between visceral and subcutaneous fat of pregnant women with spontaneous labor at term (q-value <0.1; fold change >1.5). Biological processes enriched in this comparison included tissue and vasculature development, inflammatory and metabolic pathways. Differential splicing was found for 42 genes (q-value <0.1; difference FIRMA scores >2) between adipose tissue regions of women not in labor. Differential exon usage associated with parturition was found for three genes (LIMS1, HSPA5 and GSTK1) in subcutaneous tissues. CONCLUSION We show for the first time evidence of implication of mRNA splicing and processing machinery in the subcutaneous adipose tissue of women in labor compared to those without labor. PMID:26994472

Characterization of visceral and subcutaneous adipose tissue transcriptome in pregnant women with and without spontaneous labor at term: implication of alternative splicing in the metabolic adaptations of adipose tissue to parturition.

PubMed

Mazaki-Tovi, Shali; Tarca, Adi L; Vaisbuch, Edi; Kusanovic, Juan Pedro; Than, Nandor Gabor; Chaiworapongsa, Tinnakorn; Dong, Zhong; Hassan, Sonia S; Romero, Roberto

2016-10-01

The aim of this study was to determine gene expression and splicing changes associated with parturition and regions (visceral vs. subcutaneous) of the adipose tissue of pregnant women. The transcriptome of visceral and abdominal subcutaneous adipose tissue from pregnant women at term with (n=15) and without (n=25) spontaneous labor was profiled with the Affymetrix GeneChip Human Exon 1.0 ST array. Overall gene expression changes and the differential exon usage rate were compared between patient groups (unpaired analyses) and adipose tissue regions (paired analyses). Selected genes were tested by quantitative reverse transcription-polymerase chain reaction. Four hundred and eighty-two genes were differentially expressed between visceral and subcutaneous fat of pregnant women with spontaneous labor at term (q-value <0.1; fold change >1.5). Biological processes enriched in this comparison included tissue and vasculature development as well as inflammatory and metabolic pathways. Differential splicing was found for 42 genes [q-value <0.1; differences in Finding Isoforms using Robust Multichip Analysis scores >2] between adipose tissue regions of women not in labor. Differential exon usage associated with parturition was found for three genes (LIMS1, HSPA5, and GSTK1) in subcutaneous tissues. We show for the first time evidence of implication of mRNA splicing and processing machinery in the subcutaneous adipose tissue of women in labor compared to those without labor.

Adipose tissue-derived stem cell response to the differently processed 316L stainless steel substrates.

PubMed

Faghihi, Shahab; Zia, Sonia; Taha, Masoumeh Fakhr

2012-12-01

Stainless steel (SS) is one of the most applicable materials in fabrication of cardiac implants. The aim of this study is to investigate the effect of atomic structure of polycrystalline stainless steel on the response of adipose tissue-derived stem cells (ADSCs). Samples are prepared from differently processed extruded rod and rolled sheet of 316L SS having different crystallographic structure. X-ray diffraction analysis indicated (200) and (111) orientations with distinct volume fractions in the specimens. Morphology and ADSCs behavior including adhesion, proliferation and differentiation are assessed. The expression of cardiac specific protein (cardiac troponin I) and genes of differentiating cardiomyocytes is analyzed by immunofluorescence and RT-PCR. The number of attached and grown cells on the rod sample is higher than the sheet sample also the scanning electron microscopy (SEM) analysis of ADSCs grown on the samples demonstrates higher cell density and spreading pattern on the surface of rod sample. In differentiated ADSCs on the rod sample the expression of all genes except ANF are detectable, while on the sheet sample only the MEF2C and β-MHC are expressed. This study shows that the cellular response is influenced by the crystal structure of the substrate therefore; the skill to alter the structure of substrate may lend itself to engineer a biomaterial which could be suitable for differentiation of stem cells into a definite lineage. Copyright © 2012 Elsevier Ltd. All rights reserved.

Transcriptional Reversion of Cardiac Myocyte Fate During Mammalian Cardiac Regeneration

PubMed Central

O’Meara, Caitlin C.; Wamstad, Joseph A.; Gladstone, Rachel; Fomovsky, Gregory M.; Butty, Vincent L.; Shrikumar, Avanti; Gannon, Joseph; Boyer, Laurie A.; Lee, Richard T.

2014-01-01

Rationale Neonatal mice have the capacity to regenerate their hearts in response to injury, but this potential is lost after the first week of life. The transcriptional changes that underpin mammalian cardiac regeneration have not been fully characterized at the molecular level. Objective The objectives of our study were to determine if myocytes revert the transcriptional phenotype to a less differentiated state during regeneration and to systematically interrogate the transcriptional data to identify and validate potential regulators of this process. Methods and Results We derived a core transcriptional signature of injury-induced cardiac myocyte regeneration in mouse by comparing global transcriptional programs in a dynamic model of in vitro and in vivo cardiac myocyte differentiation, in vitro cardiac myocyte explant model, as well as a neonatal heart resection model. The regenerating mouse heart revealed a transcriptional reversion of cardiac myocyte differentiation processes including reactivation of latent developmental programs similar to those observed during de-stabilization of a mature cardiac myocyte phenotype in the explant model. We identified potential upstream regulators of the core network, including interleukin 13 (IL13), which induced cardiac myocyte cell cycle entry and STAT6/STAT3 signaling in vitro. We demonstrate that STAT3/periostin and STAT6 signaling are critical mediators of IL13 signaling in cardiac myocytes. These downstream signaling molecules are also modulated in the regenerating mouse heart. Conclusions Our work reveals new insights into the transcriptional regulation of mammalian cardiac regeneration and provides the founding circuitry for identifying potential regulators for stimulating heart regeneration. PMID:25477501

Differential subsidence in Mexico City and implications to its Collective Transport System (Metro).

NASA Astrophysics Data System (ADS)

Solano Rojas, D. E.; Wdowinski, S.; Cabral-Cano, E.; Osmanoglu, B.

2017-12-01

Mexico City is one of the fastest subsiding metropolis in the world. At displacement rates ranging from 0 to -380 [mm/yr], the complex geological setting is subjected to differential subsidence, which has led to damage, operation interruptions, and accidents to the Collective Transport System, or Metro. The Metro plays a critical role in Mexico City, carrying more than four million passengers per day. However, no previous study has focused on the deformation monitoring along the 93 km of the Metro surface railways, mainly because of the limitations of the traditional geodetic techniques. In this study, we use high-resolution Interferometric Synthetic Aperture Radar (InSAR) observations to monitor land subsidence throughout the city and quantify differential subsidence along surface Metro lines. Our analysis is based on 34 TerraSAR-X StripMap scenes acquired from May 2011 to June 2013 and 36 COSMO-SkyMed Stripmap scenes acquired from June 2011 to June 2012. The data were processed using the StaMPS InSAR time series technique, obtaining point densities of up to 4827 points/km2. Our post-processing methodologies include the following two components: (1) Detection of differential subsidence along the metro lines by calculating subsidence gradients, and (2) Detection of apparent uplift—areas subsiding slower than their surroundings—by using spatial frequency filtering. The two analyses allow us to recognize four main consequences of differential subsidence in the Metro system: 1. Deflection in elevated railways, 2. Deflection in street-level railways, 3. Columns with decreased loading capacity, and 4. Apparent uplift affecting surrounding infrastructure. Our results aim at shortening the large gap between scientific geodetic studies and applicable engineering parameters that can be used by local authorities in the city for maintenance and new lines development.

Azithromycin attenuates myofibroblast differentiation and lung fibrosis development through proteasomal degradation of NOX4.

PubMed

Tsubouchi, Kazuya; Araya, Jun; Minagawa, Shunsuke; Hara, Hiromichi; Ichikawa, Akihiro; Saito, Nayuta; Kadota, Tsukasa; Sato, Nahoko; Yoshida, Masahiro; Kurita, Yusuke; Kobayashi, Kenji; Ito, Saburo; Fujita, Yu; Utsumi, Hirofumi; Yanagisawa, Haruhiko; Hashimoto, Mitsuo; Wakui, Hiroshi; Yoshii, Yutaka; Ishikawa, Takeo; Numata, Takanori; Kaneko, Yumi; Asano, Hisatoshi; Yamashita, Makoto; Odaka, Makoto; Morikawa, Toshiaki; Nakayama, Katsutoshi; Nakanishi, Yoichi; Kuwano, Kazuyoshi

2017-08-03

Accumulation of profibrotic myofibroblasts is involved in the process of fibrosis development during idiopathic pulmonary fibrosis (IPF) pathogenesis. TGFB (transforming growth factor β) is one of the major profibrotic cytokines for myofibroblast differentiation and NOX4 (NADPH oxidase 4) has an essential role in TGFB-mediated cell signaling. Azithromycin (AZM), a second-generation antibacterial macrolide, has a pleiotropic effect on cellular processes including proteostasis. Hence, we hypothesized that AZM may regulate NOX4 levels by modulating proteostasis machineries, resulting in inhibition of TGFB-associated lung fibrosis development. Human lung fibroblasts (LF) were used to evaluate TGFB-induced myofibroblast differentiation. With respect to NOX4 regulation via proteostasis, assays for macroautophagy/autophagy, the unfolded protein response (UPR), and proteasome activity were performed. The potential anti-fibrotic property of AZM was examined by using bleomycin (BLM)-induced lung fibrosis mouse models. TGFB-induced NOX4 and myofibroblast differentiation were clearly inhibited by AZM treatment in LF. AZM-mediated NOX4 reduction was restored by treatment with MG132, a proteasome inhibitor. AZM inhibited autophagy and enhanced the UPR. Autophagy inhibition by AZM was linked to ubiquitination of NOX4 via increased protein levels of STUB1 (STIP1 homology and U-box containing protein 1), an E3 ubiquitin ligase. An increased UPR by AZM was associated with enhanced proteasome activity. AZM suppressed lung fibrosis development induced by BLM with concomitantly reduced NOX4 protein levels and enhanced proteasome activation. These results suggest that AZM suppresses NOX4 by promoting proteasomal degradation, resulting in inhibition of TGFB-induced myofibroblast differentiation and lung fibrosis development. AZM may be a candidate for the treatment of the fibrotic lung disease IPF.

Building Measures of Instructional Differentiation from Teacher Checklists

ERIC Educational Resources Information Center

Williams, Ryan; Swanlund, Andrew; Miller, Shazia; Konstantopoulos, Spyros; van der Ploeg, Arie

2012-01-01

Differentiated instruction is commonly believed to be critical to improving the quality and efficiency of teachers' instructional repertoires (Fischer & Rose, 2001; Tomlinson, 2004). Tomlinson (2000) describes differentiation in four domains: content, process, product, and learning environment. Content differentiation involves varying…

68Ga-DOTA-TOC uptake in neuroendocrine tumour and healthy tissue: differentiation of physiological uptake and pathological processes in PET/CT.

PubMed

Kroiss, A; Putzer, D; Decristoforo, C; Uprimny, C; Warwitz, B; Nilica, B; Gabriel, M; Kendler, D; Waitz, D; Widmann, G; Virgolini, I J

2013-04-01

We wanted to establish the range of (68)Ga-DOTA-TOC uptake in liver and bone metastases of patients with neuroendocrine tumours (NET) and to establish the range of its uptake in pancreatic NET. This would allow differentiation between physiological uptake and tumour-related somatostatin receptor expression in the pancreas (including the uncinate process), liver and bone. Finally, we wanted to test for differences in patients with NET, either treated or not treated with peptide receptor radionuclide therapy (PRRT). In 249 patients, 390 (68)Ga-DOTA-TOC PET/CT studies were performed. The clinical indications for PET/CT were gastroenteropancreatic NET (194 studies), nongastroenteropancreatic NET (origin in the lung and rectum; 46 studies), NET of unknown primary (111 studies), phaeochromocytoma/glomus tumours (18 studies), and radioiodine-negative metastatic thyroid carcinoma (21 studies). SUVmax (mean ± standard deviation) values of (68)Ga-DOTA-TOC were 29.8 ± 16.5 in 162 liver metastases, 19.8 ± 18.8 in 89 bone metastases and 34.6 ± 17.1 in 43 pancreatic NET (33.6 ± 14.3 in 30 tumours of the uncinate process and 36.3 ± 21.5 in 13 tumours of the pancreatic tail). A significant difference in SUVmax (p < 0.02) was found in liver metastases of NET patients treated with PRRT. There were significant differences in SUVmax between nonmalignant and malignant tissue for both bone and liver metastases and for pancreatic NET including the uncinate process (p < 0.0001). At a cut-off value of 17.1 the specificity and sensitivity of SUVmax for differentiating tumours in the uncinate process were 93.6 % and 90.0 %, respectively (p < 0.0001). (68)Ga-DOTA-TOC is an excellent tracer for the imaging of tumours expressing somatostatin receptors on the tumour cell surface, facilitating the detection of even small tumour lesions. The noninvasive PET/CT approach by measurement of regional SUVmax can offer important clinical information to distinguish between physiological and pathological somatostatin receptor expression, especially in the uncinate process. PRRT does not significantly influence SUVmax, except in liver metastases of patients with NET.

Determining the Best-Fit FPGA for a Space Mission: An Analysis of Cost, SEU Sensitivity,and Reliability

NASA Technical Reports Server (NTRS)

Berg, Melanie; LaBel, Ken

2007-01-01

This viewgraph presentation reviews the selection of the optimum Field Programmable Gate Arrays (FPGA) for space missions. Included in this review is a discussion on differentiating amongst various FPGAs, cost analysis of the various options, the investigation of radiation effects, an expansion of the evaluation criteria, and the application of the evaluation criteria to the selection process.

Getting a Grip on Memory: Unilateral Hand Clenching Alters Episodic Recall

DTIC Science & Technology

2013-04-24

States of America Abstract Unilateral hand clenching increases neuronal activity in the frontal lobe of the contralateral hemisphere. Such hand clenching...Simple clenching of one versus the other hand increases the neuronal activity of the frontal lobe in the opposite (contralateral) hemisphere [1], [2...hemispheres are thought to be differentially involved in many functions, including language , emotion, spatial processing, and local/global informa

Pharmacokinetics and RC Circuit Concepts

NASA Astrophysics Data System (ADS)

Cock, Mieke De; Janssen, Paul

2013-11-01

Most introductory physics courses include a chapter on RC circuits in which the differential equations for the charging and discharging of a capacitor are derived. A number of papers in this journal describe lab experiments dealing with the measurement of different parameters in such RC circuits. In this contribution, we report on a lab experiment we developed for students majoring in pharmacy, using RC circuits to simulate a pharmacokinetic process.

Actively generated noise liquid flowmeter.

PubMed

Tanisawa, S; Hirose, H; Yoshihisa, N

1994-01-01

A new noise flowmeter with two transducers has been tested experimentally in water. It detects the noises generated by the interaction between artificially introduced air bubbles and a built-in obstacle with a downstream transducer, and differentiates them from the external noises detected by the upstream transducer in a pipe. The system includes processing instrumentation with functions such as averaging and difference-operating for reduction of external noise effects.

Retinoid Pathway and Cancer Therapeutics

PubMed Central

Bushue, Nathan; Wan, Yu-Jui Yvonne

2010-01-01

The retinoids are a class of compounds that are structurally related to vitamin A. Retinoic acid, which is the active metabolite of retinol, regulates a wide range of biological processes including development, differentiation, proliferation, and apoptosis. Retinoids exert their effects through a variety of binding proteins including cellular retinol binding protein (CRBP), retinol-binding proteins (RBP), cellular retinoic acid-binding protein (CRABP), and nuclear receptors i.e. retinoic acid receptor (RAR) and retinoid × receptor (RXR). Because of the pleiotropic effects of retinoids, understanding the function of these binding proteins and nuclear receptors assists us in developing compounds that have specific effects. This review summarizes our current understanding of how retinoids are processed and act with the emphasis on the application of retinoids in cancer treatment and prevention. PMID:20654663

Insulin receptor-mediated signaling via phospholipase C-γ regulates growth and differentiation in Drosophila.

PubMed

Murillo-Maldonado, Juan M; Zeineddine, Fouad Bou; Stock, Rachel; Thackeray, Justin; Riesgo-Escovar, Juan R

2011-01-01

Coordination between growth and patterning/differentiation is critical if appropriate final organ structure and size is to be achieved. Understanding how these two processes are regulated is therefore a fundamental and as yet incompletely answered question. Here we show through genetic analysis that the phospholipase C-γ (PLC-γ) encoded by small wing (sl) acts as such a link between growth and patterning/differentiation by modulating some MAPK outputs once activated by the insulin pathway; particularly, sl promotes growth and suppresses ectopic differentiation in the developing eye and wing, allowing cells to attain a normal size and differentiate properly. sl mutants have previously been shown to have a combination of both growth and patterning/differentiation phenotypes: small wings, ectopic wing veins, and extra R7 photoreceptor cells. We show here that PLC-γ activated by the insulin pathway participates broadly and positively during cell growth modulating EGF pathway activity, whereas in cell differentiation PLC-γ activated by the insulin receptor negatively regulates the EGF pathway. These roles require different SH2 domains of PLC-γ, and act via classic PLC-γ signaling and EGF ligand processing. By means of PLC-γ, the insulin receptor therefore modulates differentiation as well as growth. Overall, our results provide evidence that PLC-γ acts during development at a time when growth ends and differentiation begins, and is important for proper coordination of these two processes.

Quantitative Proteomics Uncovers Novel Factors Involved in Developmental Differentiation of Trypanosoma brucei

PubMed Central

Dejung, Mario; Subota, Ines; Bucerius, Ferdinand; Dindar, Gülcin; Freiwald, Anja; Engstler, Markus; Boshart, Michael; Butter, Falk; Janzen, Christian J.

2016-01-01

Developmental differentiation is a universal biological process that allows cells to adapt to different environments to perform specific functions. African trypanosomes progress through a tightly regulated life cycle in order to survive in different host environments when they shuttle between an insect vector and a vertebrate host. Transcriptomics has been useful to gain insight into RNA changes during stage transitions; however, RNA levels are only a moderate proxy for protein abundance in trypanosomes. We quantified 4270 protein groups during stage differentiation from the mammalian-infective to the insect form and provide classification for their expression profiles during development. Our label-free quantitative proteomics study revealed previously unknown components of the differentiation machinery that are involved in essential biological processes such as signaling, posttranslational protein modifications, trafficking and nuclear transport. Furthermore, guided by our proteomic survey, we identified the cause of the previously observed differentiation impairment in the histone methyltransferase DOT1B knock-out strain as it is required for accurate karyokinesis in the first cell division during differentiation. This epigenetic regulator is likely involved in essential chromatin restructuring during developmental differentiation, which might also be important for differentiation in higher eukaryotic cells. Our proteome dataset will serve as a resource for detailed investigations of cell differentiation to shed more light on the molecular mechanisms of this process in trypanosomes and other eukaryotes. PMID:26910529

Differential associative training enhances olfactory acuity in Drosophila melanogaster.

PubMed

Barth, Jonas; Dipt, Shubham; Pech, Ulrike; Hermann, Moritz; Riemensperger, Thomas; Fiala, André

2014-01-29

Training can improve the ability to discriminate between similar, confusable stimuli, including odors. One possibility of enhancing behaviorally expressed discrimination (i.e., sensory acuity) relies on differential associative learning, during which animals are forced to detect the differences between similar stimuli. Drosophila represents a key model organism for analyzing neuronal mechanisms underlying both odor processing and olfactory learning. However, the ability of flies to enhance fine discrimination between similar odors through differential associative learning has not been analyzed in detail. We performed associative conditioning experiments using chemically similar odorants that we show to evoke overlapping neuronal activity in the fly's antennal lobes and highly correlated activity in mushroom body lobes. We compared the animals' performance in discriminating between these odors after subjecting them to one of two types of training: either absolute conditioning, in which only one odor is reinforced, or differential conditioning, in which one odor is reinforced and a second odor is explicitly not reinforced. First, we show that differential conditioning decreases behavioral generalization of similar odorants in a choice situation. Second, we demonstrate that this learned enhancement in olfactory acuity relies on both conditioned excitation and conditioned inhibition. Third, inhibitory local interneurons in the antennal lobes are shown to be required for behavioral fine discrimination between the two similar odors. Fourth, differential, but not absolute, training causes decorrelation of odor representations in the mushroom body. In conclusion, differential training with similar odors ultimately induces a behaviorally expressed contrast enhancement between the two similar stimuli that facilitates fine discrimination.

Differential roles of HIC-5 isoforms in the regulation of cell death and myotube formation during myogenesis

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

Gao Zhengliang; Deblis, Ryan; Glenn, Honor

2007-11-15

Hic-5 is a LIM-Only member of the paxillin superfamily of focal adhesion proteins. It has been shown to regulate a range of biological processes including: senescence, tumorigenesis, steroid hormone action, integrin signaling, differentiation, and apoptosis. To better understand the roles of Hic-5 during development, we initiated a detailed analysis of Hic-5 expression and function in C{sub 2}C{sub 12} myoblasts, a well-established model for myogenesis. We have found that: (1) myoblasts express at least 6 distinct Hic-5 isoforms; (2) the two predominant isoforms, Hic-5{alpha} and Hic-5{beta}, are differentially expressed during myogenesis; (3) any experimentally induced change in Hic-5 expression results inmore » a substantial increase in apoptosis during differentiation; (4) ectopic expression of Hic-5{alpha} is permissive to differentiation while expression of either Hic-5{beta} or antisense Hic-5 blocks myoblast fusion but not chemodifferentiation; (5) Hic-5 localizes to focal adhesions in C{sub 2}C{sub 12} myoblasts and perturbation of Hic-5 leads to defects in cell spreading; (6) alterations in Hic-5 expression interfere with the normal dynamics of laminin expression; and (7) ectopic laminin, but not fibronectin, can rescue the Hic-5-induced blockade of myoblast survival and differentiation. Our data demonstrate differential roles for individual Hic-5 isoforms during myogenesis and support the hypothesis that Hic-5 mediates these effects via integrin signaling.« less

Auto-Zero Differential Amplifier

NASA Technical Reports Server (NTRS)

Quilligan, Gerard T. (Inventor); Aslam, Shahid (Inventor)

2017-01-01

An autozero amplifier may include a window comparator network to monitor an output offset of a differential amplifier. The autozero amplifier may also include an integrator to receive a signal from a latched window comparator network, and send an adjustment signal back to the differential amplifier to reduce an offset of the differential amplifier.

The differentiation directions of the bone marrow stromal cells under modeling microgravity

NASA Astrophysics Data System (ADS)

Nesterenko, Olga; Rodionova, Natalia; Katkova, Olena

Within experiments on rats simulating microgravity by base load remove from back limbs (duration of the experiment 1,5 months) on marrow stromal cells cultures (ex vivo, in vitro) comprising osteogenic cells-predecessors, extracted from femurs, studied their peculiarities of the colony formation ablity, the cell structure, some cytological and ultra-structural characteristics and differentiation direction. It was found that that under microgravity conditions there is a decline of the stromal cells colony formation intensity, decrease of the colonies size and cells mitotic activity that indicates decrease of their growth potential. Both in control and in experiment the colonies were presented by population of low-differentiated cells, differentiated cells and mature cells. The comparative cytological and morphometric analysis have shown that the studied stromal cells in colonies have the smaller sizes, more elongated shape, and higher nucleocytoplasmic ratio. Cells composition in the experiment colonies is reliably different by the ratio of the low-differentiating to being differentiated cells; a ratio of low-differentiated to already differentiated cells; ratio of differentiated cells to total number of all cells. In comparison with control group, amount of the cells passed trough a differentiation stage and mature cells in colonies is decreased by 3 to 4 times. Among the differentiated stromal cells in colonies increasing amount of adipocytes was revealed. The analysis of electron microscope microphotographs showed that in osteogenic cells differentiated under microgravity conditions, there is a reduction of the specific volume of a granular endoplasmic reticulum, Golgi's complex and quantity of nuclei reduction that indicates depression of the specific biosyntheses process intensity in cells. The increase of lysosomes and myelinic structures quantity is linked to organelles partial reduction. Consolidation of mitochondrias is an evidence of the cells’ energy metabolism disorder. In differentiated cells, disorganization and a cytoskeleton destruction was observed. Results showed that under microgravity conditions proliferative and differentiation (including osteogenic) potentialities of low-differentiated marrow stromal cells decreased, induction of their adipocytic differentiation was observes as well. Obtained results make a new contribution into gravitation sensitivity mechanisms understanding for stromal cells of the bone marrow which contain osteogenic cells- predecessors, features of the osteoporosis development.

Small GTPase Tc10 and its homologue RhoT induce N-WASP-mediated long process formation and neurite outgrowth.

PubMed

Abe, Tomoyuki; Kato, Masayoshi; Miki, Hiroaki; Takenawa, Tadaomi; Endo, Takeshi

2003-01-01

Rho family small GTPases regulate multiple cellular functions through reorganization of the actin cytoskeleton. Among them, Cdc42 and Tc10 induce filopodia or peripheral processes in cultured cells. We have identified a member of the family, designated as RhoT, which is closely related to Tc10. Tc10 was highly expressed in muscular tissues and brain and remarkably induced during differentiation of C2 skeletal muscle cells and neuronal differentiation of PC12 and N1E-115 cells. On the other hand, RhoT was predominantly expressed in heart and uterus and induced during neuronal differentiation of N1E-115 cells. Tc10 exogenously expressed in fibroblasts generated actin-filament-containing peripheral processes longer than the Cdc42-formed filopodia, whereas RhoT produced much longer and thicker processes containing actin filaments. Furthermore, both Tc10 and RhoT induced neurite outgrowth in PC12 and N1E-115 cells, but Cdc42 did not do this by itself. Tc10 and RhoT as well as Cdc42 bound to the N-terminal CRIB-motif-containing portion of N-WASP and activated N-WASP to induce Arp2/3-complex-mediated actin polymerization. The formation of peripheral processes and neurites by Tc10 and RhoT was prevented by the coexpression of dominant-negative mutants of N-WASP. Thus, N-WASP is essential for the process formation and neurite outgrowth induced by Tc10 and RhoT. Neuronal differentiation of PC12 and N1E-115 cells induced by dibutyryl cyclic AMP and by serum starvation, respectively, was prevented by dominant-negative Cdc42, Tc10 and RhoT. Taken together, all these Rho family proteins are required for neuronal differentiation, but they exert their functions differentially in process formation and neurite extension. Consequently, N-WASP activated by these small GTPases mediates neuronal differentiation in addition to its recently identified role in glucose uptake.

ZNF281 inhibits neuronal differentiation and is a prognostic marker for neuroblastoma.

PubMed

Pieraccioli, Marco; Nicolai, Sara; Pitolli, Consuelo; Agostini, Massimiliano; Antonov, Alexey; Malewicz, Michal; Knight, Richard A; Raschellà, Giuseppe; Melino, Gerry

2018-06-25

Derangement of cellular differentiation because of mutation or inappropriate expression of specific genes is a common feature in tumors. Here, we show that the expression of ZNF281, a zinc finger factor involved in several cellular processes, decreases during terminal differentiation of murine cortical neurons and in retinoic acid-induced differentiation of neuroblastoma (NB) cells. The ectopic expression of ZNF281 inhibits the neuronal differentiation of murine cortical neurons and NB cells, whereas its silencing causes the opposite effect. Furthermore, TAp73 inhibits the expression of ZNF281 through miR34a. Conversely, MYCN promotes the expression of ZNF281 at least in part by inhibiting miR34a. These findings imply a functional network that includes p73, MYCN, and ZNF281 in NB cells, where ZNF281 acts by negatively affecting neuronal differentiation. Array analysis of NB cells silenced for ZNF281 expression identified GDNF and NRP2 as two transcriptional targets inhibited by ZNF281. Binding of ZNF281 to the promoters of these genes suggests a direct mechanism of repression. Bioinformatic analysis of NB datasets indicates that ZNF281 expression is higher in aggressive, undifferentiated stage 4 than in localized stage 1 tumors supporting a central role of ZNF281 in affecting the differentiation of NB. Furthermore, patients with NB with high expression of ZNF281 have a poor clinical outcome compared with low-expressors. These observations suggest that ZNF281 is a controller of neuronal differentiation that should be evaluated as a prognostic marker in NB. Copyright © 2018 the Author(s). Published by PNAS.

Dehydroepiandrosterone exerts antiglucocorticoid action on human preadipocyte proliferation, differentiation, and glucose uptake

PubMed Central

McNelis, Joanne C.; Manolopoulos, Konstantinos N.; Gathercole, Laura L.; Bujalska, Iwona J.; Stewart, Paul M.; Tomlinson, Jeremy W.

2013-01-01

Glucocorticoids increase adipocyte proliferation and differentiation, a process underpinned by the local reactivation of inactive cortisone to active cortisol within adipocytes catalyzed by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The adrenal sex steroid precursor dehydroepiandrosterone (DHEA) has been shown to inhibit 11β-HSD1 in murine adipocytes; however, rodent adrenals do not produce DHEA physiologically. Here, we aimed to determine the effects and underlying mechanisms of the potential antiglucocorticoid action of DHEA and its sulfate ester DHEAS in human preadipocytes. Utilizing a human subcutaneous preadipocyte cell line, Chub-S7, we examined the metabolism and effects of DHEA in human adipocytes, including adipocyte proliferation, differentiation, 11β-HSD1 expression, and activity and glucose uptake. DHEA, but not DHEAS, significantly inhibited preadipocyte proliferation via cell cycle arrest in the G1 phase independent of sex steroid and glucocorticoid receptor activation. 11β-HSD1 oxoreductase activity in differentiated adipocytes was inhibited by DHEA. DHEA coincubated with cortisone significantly inhibited preadipocyte differentiation, which was assessed by the expression of markers of early (LPL) and terminal (G3PDH) adipocyte differentiation. Coincubation with cortisol, negating the requirement for 11β-HSD1 oxoreductase activity, diminished the inhibitory effect of DHEA. Further consistent with glucocorticoid-opposing effects of DHEA, insulin-independent glucose uptake was significantly enhanced by DHEA treatment. DHEA increases basal glucose uptake and inhibits human preadipocyte proliferation and differentiation, thereby exerting an antiglucocorticoid action. DHEA inhibition of the amplification of glucocorticoid action mediated by 11β-HSD1 contributes to the inhibitory effect of DHEA on human preadipocyte differentiation. PMID:24022868

Modeling evolution of the mind and cultures: emotional Sapir-Whorf hypothesis

NASA Astrophysics Data System (ADS)

Perlovsky, Leonid I.

2009-05-01

Evolution of cultures is ultimately determined by mechanisms of the human mind. The paper discusses the mechanisms of evolution of language from primordial undifferentiated animal cries to contemporary conceptual contents. In parallel with differentiation of conceptual contents, the conceptual contents were differentiated from emotional contents of languages. The paper suggests the neural brain mechanisms involved in these processes. Experimental evidence and theoretical arguments are discussed, including mathematical approaches to cognition and language: modeling fields theory, the knowledge instinct, and the dual model connecting language and cognition. Mathematical results are related to cognitive science, linguistics, and psychology. The paper gives an initial mathematical formulation and mean-field equations for the hierarchical dynamics of both the human mind and culture. In the mind heterarchy operation of the knowledge instinct manifests through mechanisms of differentiation and synthesis. The emotional contents of language are related to language grammar. The conclusion is an emotional version of Sapir-Whorf hypothesis. Cultural advantages of "conceptual" pragmatic cultures, in which emotionality of language is diminished and differentiation overtakes synthesis resulting in fast evolution at the price of self doubts and internal crises are compared to those of traditional cultures where differentiation lags behind synthesis, resulting in cultural stability at the price of stagnation. Multi-language, multi-ethnic society might combine the benefits of stability and fast differentiation. Unsolved problems and future theoretical and experimental directions are discussed.

Ectopic Activation of Wnt/β-Catenin Signaling in Lens Fiber Cells Results in Cataract Formation and Aberrant Fiber Cell Differentiation

PubMed Central

Antosova, Barbora; Smolikova, Jana; Borkovcova, Romana; Strnad, Hynek; Lachova, Jitka; Machon, Ondrej; Kozmik, Zbynek

2013-01-01

The Wnt/β-catenin signaling pathway controls many processes during development, including cell proliferation, cell differentiation and tissue homeostasis, and its aberrant regulation has been linked to various pathologies. In this study we investigated the effect of ectopic activation of Wnt/β-catenin signaling during lens fiber cell differentiation. To activate Wnt/β-catenin signaling in lens fiber cells, the transgenic mouse referred to as αA-CLEF was generated, in which the transactivation domain of β-catenin was fused to the DNA-binding protein LEF1, and expression of the transgene was controlled by αA-crystallin promoter. Constitutive activation of Wnt/β-catenin signaling in lens fiber cells of αA-CLEF mice resulted in abnormal and delayed fiber cell differentiation. Moreover, adult αA-CLEF mice developed cataract, microphthalmia and manifested downregulated levels of γ-crystallins in lenses. We provide evidence of aberrant expression of cell cycle regulators in embryonic lenses of αA-CLEF transgenic mice resulting in the delay in cell cycle exit and in the shift of fiber cell differentiation to the central fiber cell compartment. Our results indicate that precise regulation of the Wnt/β-catenin signaling activity during later stages of lens development is essential for proper lens fiber cell differentiation and lens transparency. PMID:24205179

An essential role for UTX in resolution and activation of bivalent promoters

PubMed Central

Dhar, Shilpa S.; Lee, Sung-Hun; Chen, Kaifu; Zhu, Guangjing; Oh, WonKyung; Allton, Kendra; Gafni, Ohad; Kim, Young Zoon; Tomoiga, Alin S.; Barton, Michelle Craig; Hanna, Jacob H.; Wang, Zhibin; Li, Wei; Lee, Min Gyu

2016-01-01

Trimethylated histone H3 lysine 27 (H3K27me3) is linked to gene silencing, whereas H3K4me3 is associated with gene activation. These two marks frequently co-occupy gene promoters, forming bivalent domains. Bivalency signifies repressed but activatable states of gene expression and can be resolved to active, H3K4me3-prevalent states during multiple cellular processes, including differentiation, development and epithelial mesenchymal transition. However, the molecular mechanism underlying bivalency resolution remains largely unknown. Here, we show that the H3K27 demethylase UTX (also called KDM6A) is required for the resolution and activation of numerous retinoic acid (RA)-inducible bivalent genes during the RA-driven differentiation of mouse embryonic stem cells (ESCs). Notably, UTX loss in mouse ESCs inhibited the RA-driven bivalency resolution and activation of most developmentally critical homeobox (Hox) a–d genes. The UTX-mediated resolution and activation of many bivalent Hox genes during mouse ESC differentiation were recapitulated during RA-driven differentiation of human NT2/D1 embryonal carcinoma cells. In support of the importance of UTX in bivalency resolution, Utx-null mouse ESCs and UTX-depleted NT2/D1 cells displayed defects in RA-driven cellular differentiation. Our results define UTX as a bivalency-resolving histone modifier necessary for stem cell differentiation. PMID:26762983

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

Scaling and scale invariance of conservation laws in Reynolds transport theorem framework

NASA Astrophysics Data System (ADS)

Haltas, Ismail; Ulusoy, Suleyman

2015-07-01

Scale invariance is the case where the solution of a physical process at a specified time-space scale can be linearly related to the solution of the processes at another time-space scale. Recent studies investigated the scale invariance conditions of hydrodynamic processes by applying the one-parameter Lie scaling transformations to the governing equations of the processes. Scale invariance of a physical process is usually achieved under certain conditions on the scaling ratios of the variables and parameters involved in the process. The foundational axioms of hydrodynamics are the conservation laws, namely, conservation of mass, conservation of linear momentum, and conservation of energy from continuum mechanics. They are formulated using the Reynolds transport theorem. Conventionally, Reynolds transport theorem formulates the conservation equations in integral form. Yet, differential form of the conservation equations can also be derived for an infinitesimal control volume. In the formulation of the governing equation of a process, one or more than one of the conservation laws and, some times, a constitutive relation are combined together. Differential forms of the conservation equations are used in the governing partial differential equation of the processes. Therefore, differential conservation equations constitute the fundamentals of the governing equations of the hydrodynamic processes. Applying the one-parameter Lie scaling transformation to the conservation laws in the Reynolds transport theorem framework instead of applying to the governing partial differential equations may lead to more fundamental conclusions on the scaling and scale invariance of the hydrodynamic processes. This study will investigate the scaling behavior and scale invariance conditions of the hydrodynamic processes by applying the one-parameter Lie scaling transformation to the conservation laws in the Reynolds transport theorem framework.

The Nature of Grand Minima and Maxima from Fully Nonlinear Flux Transport Dynamos

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

Inceoglu, Fadil; Arlt, Rainer; Rempel, Matthias, E-mail: finceoglu@aip.de

We aim to investigate the nature and occurrence characteristics of grand solar minimum and maximum periods, which are observed in the solar proxy records such as {sup 10}Be and {sup 14}C, using a fully nonlinear Babcock–Leighton type flux transport dynamo including momentum and entropy equations. The differential rotation and meridional circulation are generated from the effect of turbulent Reynolds stress and are subjected to back-reaction from the magnetic field. To generate grand minimum- and maximum-like periods in our simulations, we used random fluctuations in the angular momentum transport process, namely the Λ-mechanism, and in the Babcock–Leighton mechanism. To characterize themore » nature and occurrences of the identified grand minima and maxima in our simulations, we used the waiting time distribution analyses, which reflect whether the underlying distribution arises from a random or a memory-bearing process. The results show that, in the majority of the cases, the distributions of grand minima and maxima reveal that the nature of these events originates from memoryless processes. We also found that in our simulations the meridional circulation speed tends to be smaller during grand maximum, while it is faster during grand minimum periods. The radial differential rotation tends to be larger during grand maxima, while it is smaller during grand minima. The latitudinal differential rotation, on the other hand, is found to be larger during grand minima.« less

Functional Definition of Progenitors Versus Mature Endothelial Cells Reveals Key SoxF-Dependent Differentiation Process.

PubMed

Patel, Jatin; Seppanen, Elke J; Rodero, Mathieu P; Wong, Ho Yi; Donovan, Prudence; Neufeld, Zoltan; Fisk, Nicholas M; Francois, Mathias; Khosrotehrani, Kiarash

2017-02-21

During adult life, blood vessel formation is thought to occur via angiogenic processes involving branching from existing vessels. An alternate proposal suggests that neovessels form from endothelial progenitors able to assemble the intimal layers. We here aimed to define vessel-resident endothelial progenitors in vivo in a variety of tissues in physiological and pathological situations such as normal aorta, lungs, and wound healing, tumors, and placenta, as well. Based on protein expression levels of common endothelial markers using flow cytometry, 3 subpopulations of endothelial cells could be identified among VE-Cadherin+ and CD45- cells. Lineage tracing by using Cdh5cre ERt2 /Rosa-YFP reporter strategy demonstrated that the CD31-/loVEGFR2lo/intracellular endothelial population was indeed an endovascular progenitor (EVP) of an intermediate CD31intVEGFR2lo/intracellular transit amplifying (TA) and a definitive differentiated (D) CD31hiVEGFR2hi/extracellular population. EVP cells arose from vascular-resident beds that could not be transferred by bone marrow transplantation. Furthermore, EVP displayed progenitor-like status with a high proportion of cells in a quiescent cell cycle phase as assessed in wounds, tumors, and aorta. Only EVP cells and not TA and D cells had self-renewal capacity as demonstrated by colony-forming capacity in limiting dilution and by transplantation in Matrigel plugs in recipient mice. RNA sequencing revealed prominent gene expression differences between EVP and D cells. In particular, EVP cells highly expressed genes related to progenitor function including Sox9 , Il33 , Egfr , and Pdfgrα. Conversely, D cells highly expressed genes related to differentiated endothelium including Ets1&2 , Gata2 , Cd31 , Vwf , and Notch . The RNA sequencing also pointed to an essential role of the Sox18 transcription factor. The role of SOX18 in the differentiation process was validated by using lineage-tracing experiments based on S ox18Cre ERt2 /Rosa-YFP mice. Besides, in the absence of functional SOX18/SOXF, EVP progenitors were still present, but TA and D populations were significantly reduced. Our findings support an entirely novel endothelial hierarchy, from EVP to TA to D, as defined by self-renewal, differentiation, and molecular profiling of an endothelial progenitor. This paradigm shift in our understanding of vascular-resident endothelial progenitors in tissue regeneration opens new avenues for better understanding of cardiovascular biology. © 2016 American Heart Association, Inc.

Stretchy Proteins on Stretchy Substrates: The Important Elements of Integrin-Mediated Rigidity Sensing

PubMed Central

Moore, Simon W.; Roca-Cusachs, Pere; Sheetz, Michael P.

2013-01-01

Matrix and tissue rigidity guides many cellular processes, including the differentiation of stem cells and the migration of cells in health and disease. Cells actively and transiently test rigidity using mechanisms limited by inherent physical parameters that include the strength of extracellular attachments, the pulling capacity on these attachments, and the sensitivity of the mechanotransduction system. Here we focus on rigidity sensing mediated through the integrin family of extracellular matrix receptors and linked proteins, and discuss the evidence supporting these proteins as mechanosensors. PMID:20708583

Rapamycin regulates autophagy and cell adhesion in induced pluripotent stem cells.

PubMed

Sotthibundhu, Areechun; McDonagh, Katya; von Kriegsheim, Alexander; Garcia-Munoz, Amaya; Klawiter, Agnieszka; Thompson, Kerry; Chauhan, Kapil Dev; Krawczyk, Janusz; McInerney, Veronica; Dockery, Peter; Devine, Michael J; Kunath, Tilo; Barry, Frank; O'Brien, Timothy; Shen, Sanbing

2016-11-15

Cellular reprogramming is a stressful process, which requires cells to engulf somatic features and produce and maintain stemness machineries. Autophagy is a process to degrade unwanted proteins and is required for the derivation of induced pluripotent stem cells (iPSCs). However, the role of autophagy during iPSC maintenance remains undefined. Human iPSCs were investigated by microscopy, immunofluorescence, and immunoblotting to detect autophagy machinery. Cells were treated with rapamycin to activate autophagy and with bafilomycin to block autophagy during iPSC maintenance. High concentrations of rapamycin treatment unexpectedly resulted in spontaneous formation of round floating spheres of uniform size, which were analyzed for differentiation into three germ layers. Mass spectrometry was deployed to reveal altered protein expression and pathways associated with rapamycin treatment. We demonstrate that human iPSCs express high basal levels of autophagy, including key components of APMKα, ULK1/2, BECLIN-1, ATG13, ATG101, ATG12, ATG3, ATG5, and LC3B. Block of autophagy by bafilomycin induces iPSC death and rapamycin attenuates the bafilomycin effect. Rapamycin treatment upregulates autophagy in iPSCs in a dose/time-dependent manner. High concentration of rapamycin reduces NANOG expression and induces spontaneous formation of round and uniformly sized embryoid bodies (EBs) with accelerated differentiation into three germ layers. Mass spectrometry analysis identifies actin cytoskeleton and adherens junctions as the major targets of rapamycin in mediating iPSC detachment and differentiation. High levels of basal autophagy activity are present during iPSC derivation and maintenance. Rapamycin alters expression of actin cytoskeleton and adherens junctions, induces uniform EB formation, and accelerates differentiation. IPSCs are sensitive to enzyme dissociation and require a lengthy differentiation time. The shape and size of EBs also play a role in the heterogeneity of end cell products. This research therefore highlights the potential of rapamycin in producing uniform EBs and in shortening iPSC differentiation duration.

Galectin-3 drives oligodendrocyte differentiation to control myelin integrity and function

PubMed Central

Pasquini, L A; Millet, V; Hoyos, H C; Giannoni, J P; Croci, D O; Marder, M; Liu, F T; Rabinovich, G A; Pasquini, J M

2011-01-01

Galectins control critical pathophysiological processes, including the progression and resolution of central nervous system (CNS) inflammation. In spite of considerable progress in dissecting their role within lymphoid organs, their functions within the inflamed CNS remain elusive. Here, we investigated the role of galectin–glycan interactions in the control of oligodendrocyte (OLG) differentiation, myelin integrity and function. Both galectin-1 and -3 were abundant in astrocytes and microglia. Although galectin-1 was abundant in immature but not in differentiated OLGs, galectin-3 was upregulated during OLG differentiation. Biochemical analysis revealed increased activity of metalloproteinases responsible for cleaving galectin-3 during OLG differentiation and modulating its biological activity. Exposure to galectin-3 promoted OLG differentiation in a dose- and carbohydrate-dependent fashion consistent with the ‘glycosylation signature' of immature versus differentiated OLG. Accordingly, conditioned media from galectin-3-expressing, but not galectin-3-deficient (Lgals3−/−) microglia, successfully promoted OLG differentiation. Supporting these findings, morphometric analysis showed a significant decrease in the frequency of myelinated axons, myelin turns (lamellae) and g-ratio in the corpus callosum and striatum of Lgals3−/− compared with wild-type (WT) mice. Moreover, the myelin structure was loosely wrapped around the axons and less smooth in Lgals3−/− mice versus WT mice. Behavior analysis revealed decreased anxiety in Lgals3−/− mice similar to that observed during early demyelination induced by cuprizone intoxication. Finally, commitment toward the oligodendroglial fate was favored in neurospheres isolated from WT but not Lgals3−/− mice. Hence, glial-derived galectin-3, but not galectin-1, promotes OLG differentiation, thus contributing to myelin integrity and function with critical implications in the recovery of inflammatory demyelinating disorders. PMID:21566659

Brain cytoplasmic RNA 1 suppresses smooth muscle differentiation and vascular development in mice.

PubMed

Wang, Yung-Chun; Chuang, Ya-Hui; Shao, Qiang; Chen, Jian-Fu; Chen, Shi-You

2018-04-13

The cardiovascular system develops during the early stages of embryogenesis, and differentiation of smooth muscle cells (SMCs) is essential for that process. SMC differentiation is critically regulated by transforming growth factor (TGF)-β/SMAD family member 3 (SMAD3) signaling, but other regulators may also play a role. For example, long noncoding RNAs (lncRNAs) regulate various cellular activities and events, such as proliferation, differentiation, and apoptosis. However, whether long noncoding RNAs also regulate SMC differentiation remains largely unknown. Here, using the murine cell line C3H10T1/2, we found that brain cytoplasmic RNA 1 (BC1) is an important regulator of SMC differentiation. BC1 overexpression suppressed, whereas BC1 knockdown promoted, TGF-β-induced SMC differentiation, as indicated by altered cell morphology and expression of multiple SMC markers, including smooth muscle α-actin (αSMA), calponin, and smooth muscle 22α (SM22α). BC1 appeared to block SMAD3 activity and inhibit SMC marker gene transcription. Mechanistically, BC1 bound to SMAD3 via RNA SMAD-binding elements (rSBEs) and thus impeded TGF-β-induced SMAD3 translocation to the nucleus. This prevented SMAD3 from binding to SBEs in SMC marker gene promoters, an essential event in SMC marker transcription. In vivo , BC1 overexpression in mouse embryos impaired vascular SMC differentiation, leading to structural defects in the artery wall, such as random breaks in the elastic lamina, abnormal collagen deposition on SM fibers, and disorganized extracellular matrix proteins in the media of the neonatal aorta. Our results suggest that BC1 is a suppressor of SMC differentiation during vascular development. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Induction of hepatocyte-like cells from mouse embryonic stem cells by lentivirus-mediated constitutive expression of Foxa2/Hnf4a.

PubMed

Liu, Tao; Zhang, Shichang; Xiang, Dedong; Wang, Yingjie

2013-11-01

Hepatocytes can be generated from embryonic stem cells (ESCs) using inducers such as chemical compounds and cytokines, but issues related to low differentiation efficiencies remain to be resolved. Recent work has shown that overexpression of lineage-specific transcription factors can directly cause cells phenotypic changes, including differentiation, trans-differentiation, and de-differentiation. We hypothesized that lentivirus-mediated constitutive expression of forkhead box A2 (Foxa2) and hepatocyte nuclear factor 4 alpha (Hnf4a) could promote inducing mouse ESCs to hepatocyte-likes cells. First, ESC lines that stably expressed Foxa2, Hnf4a, or Foxa2/Hnf4a were constructed via lentiviral expression vectors. Second, observations of cell morphology changes were made during the cell culture process, followed by experiments examining teratoma formation. Then, the effects of constitutive expression of Foxa2 and Hnf4a on hepatic differentiation and maturation were determined by measuring the marker gene expression levels of Albumin, α-fetoprotein, Cytokeratin18, and α1-antitrypsin. The results indicate that constitutive expression of Foxa2 and Hnf4a does not affect ESCs culture, teratoma formation, or the expression levels of the specific hepatocyte genes under autonomous differentiation. However, with some assistance from inducing factors, Foxa2 significantly increased the hepatic differentiation of ESCs, whereas the expression of Hnf4a alone or Foxa2/Hnf4a could not. Differentiated CCE-Foxa2 cells were more superior in expressing several liver-specific markers and protein, storing glycogen than differentiated CCE cells. Therefore, our method employing the transduction of Foxa2 would be a valuable tool for the efficient generation of functional hepatocytes derived from ESCs. © 2013 Wiley Periodicals, Inc.

A Method for the Direct Identification of Differentiating Muscle Cells by a Fluorescent Mitochondrial Dye

PubMed Central

Miyake, Tetsuaki; McDermott, John C.; Gramolini, Anthony O.

2011-01-01

Identification of differentiating muscle cells generally requires fixation, antibodies directed against muscle specific proteins, and lengthy staining processes or, alternatively, transfection of muscle specific reporter genes driving GFP expression. In this study, we examined the possibility of using the robust mitochondrial network seen in maturing muscle cells as a marker of cellular differentiation. The mitochondrial fluorescent tracking dye, MitoTracker, which is a cell-permeable, low toxicity, fluorescent dye, allowed us to distinguish and track living differentiating muscle cells visually by epi-fluorescence microscopy. MitoTracker staining provides a robust and simple detection strategy for living differentiating cells in culture without the need for fixation or biochemical processing. PMID:22174849

RNA-seq analysis of the gonadal transcriptome during Alligator mississippiensis temperature-dependent sex determination and differentiation.

PubMed

Yatsu, Ryohei; Miyagawa, Shinichi; Kohno, Satomi; Parrott, Benjamin B; Yamaguchi, Katsushi; Ogino, Yukiko; Miyakawa, Hitoshi; Lowers, Russell H; Shigenobu, Shuji; Guillette, Louis J; Iguchi, Taisen

2016-01-25

The American alligator (Alligator mississippiensis) displays temperature-dependent sex determination (TSD), in which incubation temperature during embryonic development determines the sexual fate of the individual. However, the molecular mechanisms governing this process remain a mystery, including the influence of initial environmental temperature on the comprehensive gonadal gene expression patterns occurring during TSD. Our characterization of transcriptomes during alligator TSD allowed us to identify novel candidate genes involved in TSD initiation. High-throughput RNA sequencing (RNA-seq) was performed on gonads collected from A. mississippiensis embryos incubated at both a male and a female producing temperature (33.5 °C and 30 °C, respectively) in a time series during sexual development. RNA-seq yielded 375.2 million paired-end reads, which were mapped and assembled, and used to characterize differential gene expression. Changes in the transcriptome occurring as a function of both development and sexual differentiation were extensively profiled. Forty-one differentially expressed genes were detected in response to incubation at male producing temperature, and included genes such as Wnt signaling factor WNT11, histone demethylase KDM6B, and transcription factor C/EBPA. Furthermore, comparative analysis of development- and sex-dependent differential gene expression revealed 230 candidate genes involved in alligator sex determination and differentiation, and early details of the suspected male-fate commitment were profiled. We also discovered sexually dimorphic expression of uncharacterized ncRNAs and other novel elements, such as unique expression patterns of HEMGN and ARX. Twenty-five of the differentially expressed genes identified in our analysis were putative transcriptional regulators, among which were MYBL2, MYCL, and HOXC10, in addition to conventional sex differentiation genes such as SOX9, and FOXL2. Inferred gene regulatory network was constructed, and the gene-gene and temperature-gene interactions were predicted. Gonadal global gene expression kinetics during sex determination has been extensively profiled for the first time in a TSD species. These findings provide insights into the genetic framework underlying TSD, and expand our current understanding of the developmental fate pathways during vertebrate sex determination.

Technical variables in high-throughput miRNA expression profiling: much work remains to be done.

PubMed

Nelson, Peter T; Wang, Wang-Xia; Wilfred, Bernard R; Tang, Guiliang

2008-11-01

MicroRNA (miRNA) gene expression profiling has provided important insights into plant and animal biology. However, there has not been ample published work about pitfalls associated with technical parameters in miRNA gene expression profiling. One source of pertinent information about technical variables in gene expression profiling is the separate and more well-established literature regarding mRNA expression profiling. However, many aspects of miRNA biochemistry are unique. For example, the cellular processing and compartmentation of miRNAs, the differential stability of specific miRNAs, and aspects of global miRNA expression regulation require specific consideration. Additional possible sources of systematic bias in miRNA expression studies include the differential impact of pre-analytical variables, substrate specificity of nucleic acid processing enzymes used in labeling and amplification, and issues regarding new miRNA discovery and annotation. We conclude that greater focus on technical parameters is required to bolster the validity, reliability, and cultural credibility of miRNA gene expression profiling studies.

A flow-pulse adsorption-microcalorimetry system for studies of adsorption processes on powder catalysts

NASA Astrophysics Data System (ADS)

You, Rui; Li, Zhaorui; Zeng, Hongyu; Huang, Weixin

2018-06-01

A pulse chemisorption system combining a Tian-Calvet microcalorimeter (Setaram Sensys EVO 600) and an automated chemisorption apparatus (Micromeritics Autochem II 2920) was established to accurately measure differential adsorption heats of gas molecules' chemisorption on solid surfaces in a flow-pulse mode. Owing to high sensitivity and high degree of automation in a wide range of temperatures from -100 to 600 °C, this coupled system can present adsorption heats as a function of adsorption temperature and adsorbate coverage. The functions of this system were demonstrated by successful measurements of CO adsorption heats on Pd surfaces at various temperatures and also at different CO coverages by varying the CO concentration in the pulse dose. Key parameters, including adsorption amounts, integral adsorption heats, and differential adsorption heats of CO adsorption on a Pd/CeO2 catalyst, were acquired. Our adsorption-microcalorimetry system provides a powerful technique for the investigation of adsorption processes on powder catalysts.

Fluorescence analysis of ubiquinone and its application in quality control of medical supplies

NASA Astrophysics Data System (ADS)

Timofeeva, Elvira O.; Gorbunova, Elena V.; Chertov, Aleksandr N.

2017-02-01

The presence of antioxidant issues such as redox potential imbalance in human body is a very important question for modern clinical diagnostics. Implementation of fluorescence analysis into optical diagnostics of such wide distributed in a human body antioxidant as ubiquinone is one of the steps for development of the device with a view to clinical diagnostics of redox potential. Recording of fluorescence was carried out with spectrometer using UV irradiation source with thin band (max at 287 and 330 nm) as a background radiation. Concentrations of ubiquinone from 0.25 to 2.5 mmol/l in explored samples were used for investigation. Recording data was processed using correlation analysis and differential analytical technique. The fourth derivative spectrum of fluorescence spectrum provided the basis for a multicomponent analysis of the solutions. As a technique in clinical diagnostics fluorescence analysis with processing method including differential spectrophotometry, it is step forward towards redox potential calculation and quality control in pharmacy for better health care.

Partial least squares based gene expression analysis in estrogen receptor positive and negative breast tumors.

PubMed

Ma, W; Zhang, T-F; Lu, P; Lu, S H

2014-01-01

Breast cancer is categorized into two broad groups: estrogen receptor positive (ER+) and ER negative (ER-) groups. Previous study proposed that under trastuzumab-based neoadjuvant chemotherapy, tumor initiating cell (TIC) featured ER- tumors response better than ER+ tumors. Exploration of the molecular difference of these two groups may help developing new therapeutic strategies, especially for ER- patients. With gene expression profile from the Gene Expression Omnibus (GEO) database, we performed partial least squares (PLS) based analysis, which is more sensitive than common variance/regression analysis. We acquired 512 differentially expressed genes. Four pathways were found to be enriched with differentially expressed genes, involving immune system, metabolism and genetic information processing process. Network analysis identified five hub genes with degrees higher than 10, including APP, ESR1, SMAD3, HDAC2, and PRKAA1. Our findings provide new understanding for the molecular difference between TIC featured ER- and ER+ breast tumors with the hope offer supports for therapeutic studies.

Protein profiling in potato (Solanum tuberosum L.) leaf tissues by differential centrifugation.

PubMed

Lim, Sanghyun; Chisholm, Kenneth; Coffin, Robert H; Peters, Rick D; Al-Mughrabi, Khalil I; Wang-Pruski, Gefu; Pinto, Devanand M

2012-04-06

Foliar diseases, such as late blight, result in serious threats to potato production. As such, potato leaf tissue becomes an important substrate to study biological processes, such as plant defense responses to infection. Nonetheless, the potato leaf proteome remains poorly characterized. Here, we report protein profiling of potato leaf tissues using a modified differential centrifugation approach to separate the leaf tissues into cell wall and cytoplasmic fractions. This method helps to increase the number of identified proteins, including targeted putative cell wall proteins. The method allowed for the identification of 1484 nonredundant potato leaf proteins, of which 364 and 447 were reproducibly identified proteins in the cell wall and cytoplasmic fractions, respectively. Reproducibly identified proteins corresponded to over 70% of proteins identified in each replicate. A diverse range of proteins was identified based on their theoretical pI values, molecular masses, functional classification, and biological processes. Such a protein extraction method is effective for the establishment of a highly qualified proteome profile.

Differential water sorption studies on Kevlar 49 and As-polymerized poly(p-phenylene terephthalamide): determination of water transport properties.

PubMed

Mooney, Damian A; MacElroy, J M Don

2007-11-06

Water vapor sorption experiments have been conducted on Kevlar 49 at 30 degrees C over a range of water vapor pressures in 0-90% of saturation and on the as-polymerized form of the material at 30, 45, and 60 degrees C over a series of water vapor pressures of 0-60%, 0-25%, and 0-15%, respectively. For each of the differential steps in water vapor pressure, dynamic uptake curves were generated and analyzed according to a number of different mathematical models, including Fickian, Coaxial cylindrical, and intercalation models. The intercalation model was demonstrated to be the most successful model and considered two time-scales involved in the diffusion process, i.e., a penetrant-diffusive time-scale and a polymer-local-matrix-relaxation time-scale. The success of this model reinforces previously reported adsorption and desorption isotherms which suggested that water may penetrate into the surface layers of the polymer crystallite through a process known as intercalation.

Selection of reference genes for quantitative real time RT-PCR during dimorphism in the zygomycete Mucor circinelloides.

PubMed

Valle-Maldonado, Marco I; Jácome-Galarza, Irvin E; Gutiérrez-Corona, Félix; Ramírez-Díaz, Martha I; Campos-García, Jesús; Meza-Carmen, Víctor

2015-03-01

Mucor circinelloides is a dimorphic fungal model for studying several biological processes including cell differentiation (yeast-mold transitions) as well as biodiesel and carotene production. The recent release of the first draft sequence of the M. circinelloides genome, combined with the availability of analytical methods to determine patterns of gene expression, such as quantitative Reverse transcription-Polymerase chain reaction (qRT-PCR), and the development of molecular genetic tools for the manipulation of the fungus, may help identify M. circinelloides gene products and analyze their relevance in different biological processes. However, no information is available on M. circinelloides genes of stable expression that could serve as internal references in qRT-PCR analyses. One approach to solve this problem consists in the use of housekeeping genes as internal references. However, validation of the usability of these reference genes is a fundamental step prior to initiating qRT-PCR assays. This work evaluates expression of several constitutive genes by qRT-PCR throughout the morphological differentiation stages of M. circinelloides; our results indicate that tfc-1 and ef-1 are the most stable genes for qRT-PCR assays during differentiation studies and they are proposed as reference genes to carry out gene expression studies in this fungus.

Lung Epithelial Healing: A Modified Seed and Soil Concept

PubMed Central

Brechbuhl, Heather M.; Smith, Mary Kathryn; Smith, Russell W.; Ghosh, Moumita

2012-01-01

Airway epithelial healing is defined as restoration of health or soundness; to cure. Our research indicates that two types of progenitor cells participate in this process: the tissue-specific stem cell (TSC) and the facultative basal progenitor (FBP). The TSC restores the epithelium to its normal structure and function. Thus, the TSC regenerates the epithelium. In contrast, the FBP-derived epithelium is characterized by regions of cellular hyperplasia and hypoplasia. Since the FBP-derived epithelium deviates from normal, we term the FBP-mediated process repair. Our work indicates that the TSC responds to signals from other epithelial cells, including the FBP. These signals instruct the TSC to proliferate or to select one of several differentiation pathways. We interpret these data in the context of Stephen Padget’s “seed and soil” paradigm. Therein, Padget explained that metastasis of a tumor, the seed, to a specific site, the soil, was determined by the growth and differentiation requirements of the tumor cell. By extending the seed and soil paradigm to airway epithelial healing, we suggest that proliferation and differentiation of the TSC, the seed, is determined by its interactions with other cell types, the soil. Based on this concept, we provide a set of suggestions for development of cell-based therapies that are directed toward chronic airways disease. PMID:22550238

Exposure to low pH induces molecular level changes in the marine worm, Platynereis dumerilii.

PubMed

Wäge, Janine; Lerebours, Adelaide; Hardege, Jörg D; Rotchell, Jeanette M

2016-02-01

Fossil fuel emissions and changes in net land use lead to an increase in atmospheric CO2 concentration and a subsequent decrease of ocean pH. Noticeable effects on organisms' calcification rate, shell structure and energy metabolism have been reported in the literature. To date, little is known about the molecular mechanisms altered under low pH exposure, especially in non-calcifying organisms. We used a suppression subtractive hybridisation (SSH) approach to characterise differentially expressed genes isolated from Platynereis dumerilii, a non-calcifying marine polychaeta species, kept at normal and low pH conditions. Several gene sequences have been identified as differentially regulated. These are involved in processes previously considered as indicators of environment change, such as energy metabolism (NADH dehydrogenase, 2-oxoglutarate dehydrogenase, cytochrome c oxidase and ATP synthase subunit F), while others are involved in cytoskeleton function (paramyosin and calponin) and immune defence (fucolectin-1 and paneth cell-specific alpha-defensin) processes. This is the first study of differential gene expression in a non-calcifying, marine polychaete exposed to low pH seawater conditions and suggests that mechanisms of impact may include additional pathways not previously identified as impacted by low pH in other species. Copyright © 2015 Elsevier Inc. All rights reserved.

[Vascular Calcification - Pathological Mechanism and Clinical Application - . Role of vascular smooth muscle cells in vascular calcification].

PubMed

Kurabayashi, Masahiko

2015-05-01

Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area.

Clostridium botulinum and the clinical laboratorian: a detailed review of botulism, including biological warfare ramifications of botulinum toxin.

PubMed

Caya, James G; Agni, Rashmi; Miller, Joan E

2004-06-01

This review article is designed to thoroughly familiarize all health care professionals with the history, classification, epidemiology, clinical characteristics, differential diagnosis, diagnostic evaluation (including laboratory-based testing), treatment, and prognosis of botulism. It is especially targeted toward clinical laboratorians and includes a detailed enumeration of the important clinical laboratory contributions to the diagnosis, treatment, and monitoring of patients with botulism. Finally, the bioterrorism potential for botulism is discussed, with an emphasis on the clinical laboratory ramifications of this possibility. Included medical periodicals and textbooks accessioned from computerized and manual medical literature searches. More than 1000 medical works published from the 1800s through 2003 were retrieved and reviewed in this process. Pertinent data are presented in textual and tabular formats, the latter including 6 tables presenting detailed information regarding the clinical parameters, differential diagnosis, diagnostic studies, laboratory testing, and therapeutic approaches to botulism. Because botulism is such a rare disease, a keen awareness of its manifestations and prompt diagnosis are absolutely crucial for its successful treatment. The bioterrorism potential of botulism adds further urgency to the need for all health care professionals to be familiar with this disease, its proper evaluation, and timely treatment; the need for such urgency clearly includes the clinical laboratory.

Mathematical Modelling of Continuous Biotechnological Processes

ERIC Educational Resources Information Center

Pencheva, T.; Hristozov, I.; Shannon, A. G.

2003-01-01

Biotechnological processes (BTP) are characterized by a complicated structure of organization and interdependent characteristics. Partial differential equations or systems of partial differential equations are used for their behavioural description as objects with distributed parameters. Modelling of substrate without regard to dispersion…

Sibling differentiation, identity development, and the lateral dimension of psychic life.

PubMed

Vivona, Jeanine M

2007-01-01

The lateral dimension of psychic life, lived through relationships with siblings and their substitutes, is structured around a distinct psychic challenge: to find one's unique place in a world of similar others. Like the challenge that structures the vertical parent-child dimension, the lateral challenge is fraught with conflict and ambivalence; its resolution imbues psychic structure. That resolution may be accomplished through a process of differentiation, an active and unconscious process of identity development by which a child amplifies differences with siblings and minimizes similarities. Differentiation from siblings serves to mitigate interpersonal rivalry with them and to ease internal conflict associated with the lateral dimension. Three clinical examples are offered to illustrate the operation of sibling differentiation and its costs, particularly in terms of constricted identity and attenuated relationships with siblings and peers. Differentiation as a process of becoming what the other is not has been eclipsed by identification in psychoanalytic theories of identity development. Yet differentiation is a common strategy for resolving the primary rivalries and conflicts of the lateral dimension, and has unique developmental and clinical implications.

A data processing method based on tracking light spot for the laser differential confocal component parameters measurement system

NASA Astrophysics Data System (ADS)

Shao, Rongjun; Qiu, Lirong; Yang, Jiamiao; Zhao, Weiqian; Zhang, Xin

2013-12-01

We have proposed the component parameters measuring method based on the differential confocal focusing theory. In order to improve the positioning precision of the laser differential confocal component parameters measurement system (LDDCPMS), the paper provides a data processing method based on tracking light spot. To reduce the error caused by the light point moving in collecting the axial intensity signal, the image centroiding algorithm is used to find and track the center of Airy disk of the images collected by the laser differential confocal system. For weakening the influence of higher harmonic noises during the measurement, Gaussian filter is used to process the axial intensity signal. Ultimately the zero point corresponding to the focus of the objective in a differential confocal system is achieved by linear fitting for the differential confocal axial intensity data. Preliminary experiments indicate that the method based on tracking light spot can accurately collect the axial intensity response signal of the virtual pinhole, and improve the anti-interference ability of system. Thus it improves the system positioning accuracy.

Adolescent aggression and differentiation of self: guided mindfulness meditation in the service of individuation.

PubMed

Birnbaum, Liora

2005-06-23

This paper presents adolescent aggression as mediated by the level of differentiation of self. No research has directly addressed Bowen's notion that level of differentiation impacts child functioning including aggression. Level of differentiation is discussed in conjunction with social, gender and cultural norms as manifested in aggressive behavior. Female adolescent aggression is described as mainly relationship focused and expressed via verbal threats, intimidation and manipulation, while male aggression is described mainly as overt physical violence involving dominance and competitiveness. Research on differentiation focuses mainly on Western cultures that tend to be individualistic. Jewish-Israeli society is in transition from collectivistic to individualistic cultural values in the midst of ongoing hostilities. These processes create conflict regarding togetherness and individuality needs among adolescents, who are exposed to contradictory messages regarding separating and staying close. External as well as internal expressions of aggression (depression, suicide) are presented as coping strategies in the service of a wounded self-negotiating with the world. Guided mindfulness meditation is a powerful technique for facilitating healing and growth toward autonomy by helping adolescents connect to their inner voice. This technique may be especially useful in the adolescent search for self-awareness, meaning and life purpose. Bodily, cognitive and emotional experiences are treated as informative regarding the 'self' and facilitate expansion of self-perception and individuality.

Prmt7 is dispensable in tissue culture models for adipogenic differentiation.

PubMed

Hu, Yu-Jie; Sif, Saïd; Imbalzano, Anthony N

2013-01-01

Protein arginine methylation is a common posttranslational modification that has been implicated in numerous biological processes including gene expression. The mammalian genome encodes nine protein arginine methyltransferases (Prmts) that catalyze monomethylation, asymmetric dimethylation, and symmetric dimethylation on arginine residues. Protein arginine methyltransferase 7 (Prmt7) is categorized as a type II and type III enzyme that produces symmetric dimethylated arginine and monomethylated arginine, respectively. However, the biological role of Prmt7 is not well characterized. We previously showed that Prmt5, a type II Prmt that associates with Brg1-based SWI/SNF chromatin remodeling complex, is required for adipocyte differentiation. Since Prmt7 also associates with Brg1-based SWI/SNF complex and modifies core histones, we hypothesized that Prmt7 might play a role in transcriptional regulation of adipogenesis. In the present study, we determined that the expression of Prmt7 did not change throughout adipogenic differentiation of C3H10T1/2 mesenchymal cells. Knockdown or over-expression of Prmt7 had no effect on lipid accumulation or adipogenic gene expression in differentiating C3H10T1/2 cells or in C/EBPα-reprogrammed NIH3T3 fibroblasts. Based on these results, we conclude that Prmt7, unlike Prmt5, is dispensable for adipogenic differentiation in tissue culture models.

Prmt7 is dispensable in tissue culture models for adipogenic differentiation

PubMed Central

Imbalzano, Anthony N.

2013-01-01

Protein arginine methylation is a common posttranslational modification that has been implicated in numerous biological processes including gene expression. The mammalian genome encodes nine protein arginine methyltransferases (Prmts) that catalyze monomethylation, asymmetric dimethylation, and symmetric dimethylation on arginine residues. Protein arginine methyltransferase 7 (Prmt7) is categorized as a type II and type III enzyme that produces symmetric dimethylated arginine and monomethylated arginine, respectively. However, the biological role of Prmt7 is not well characterized. We previously showed that Prmt5, a type II Prmt that associates with Brg1-based SWI/SNF chromatin remodeling complex, is required for adipocyte differentiation. Since Prmt7 also associates with Brg1-based SWI/SNF complex and modifies core histones, we hypothesized that Prmt7 might play a role in transcriptional regulation of adipogenesis. In the present study, we determined that the expression of Prmt7 did not change throughout adipogenic differentiation of C3H10T1/2 mesenchymal cells. Knockdown or over-expression of Prmt7 had no effect on lipid accumulation or adipogenic gene expression in differentiating C3H10T1/2 cells or in C/EBPα-reprogrammed NIH3T3 fibroblasts. Based on these results, we conclude that Prmt7, unlike Prmt5, is dispensable for adipogenic differentiation in tissue culture models. PMID:24715966

Genetic structure and isolation by altitude in rice landraces of Yunnan, China revealed by nucleotide and microsatellite marker polymorphisms

PubMed Central

A, Xinxiang; Yu, Tengqiong; Ma, Xiaoding; Zhang, Enlai; Wang, Yanjie; Cao, Guilan; Xu, Furong; Dai, Luyuan; Han, Longzhi

2017-01-01

Rice landraces, a genetic reservoir for varietal improvement, are developed by farmers through artificial selection during the long-term domestication process. To efficiently conserve, manage, and use such germplasm resources, an understanding of the genetic structure and differentiation of local rice landraces is required. In this study, we analyzed 188 accessions of rice landraces collected from localities across an altitudinal gradient from 425 to 2, 274 m above sea level in Yunnan Province, China using ten target genes and 48 SSR markers. We detected clear differentiation of the rice landraces into indica and japonica groups and further separation of the accessions in each group into two subgroups according to altitude, including a lower altitude subgroup and higher altitude subgroup. The AMOVA results showed significant genetic differentiation among altitude zones at SSRs and most genes, except Os1977 and STS22. We further determined that differentiation among landrace populations followed a model of isolation by altitude, in which gene flow was higher among populations at similar altitude levels than across different altitude levels. Our findings demonstrated that both adaptation to altitude and altitude-dependent gene flow played key roles in the genetic differentiation of rice landraces in Yunnan, China. PMID:28423046

Genetic structure and isolation by altitude in rice landraces of Yunnan, China revealed by nucleotide and microsatellite marker polymorphisms.

PubMed

Cui, Di; Tang, Cuifeng; Li, Jinmei; A, Xinxiang; Yu, Tengqiong; Ma, Xiaoding; Zhang, Enlai; Wang, Yanjie; Cao, Guilan; Xu, Furong; Dai, Luyuan; Han, Longzhi; Koh, Hee-Jong

2017-01-01

Rice landraces, a genetic reservoir for varietal improvement, are developed by farmers through artificial selection during the long-term domestication process. To efficiently conserve, manage, and use such germplasm resources, an understanding of the genetic structure and differentiation of local rice landraces is required. In this study, we analyzed 188 accessions of rice landraces collected from localities across an altitudinal gradient from 425 to 2, 274 m above sea level in Yunnan Province, China using ten target genes and 48 SSR markers. We detected clear differentiation of the rice landraces into indica and japonica groups and further separation of the accessions in each group into two subgroups according to altitude, including a lower altitude subgroup and higher altitude subgroup. The AMOVA results showed significant genetic differentiation among altitude zones at SSRs and most genes, except Os1977 and STS22. We further determined that differentiation among landrace populations followed a model of isolation by altitude, in which gene flow was higher among populations at similar altitude levels than across different altitude levels. Our findings demonstrated that both adaptation to altitude and altitude-dependent gene flow played key roles in the genetic differentiation of rice landraces in Yunnan, China.

Differentiating the Spatiotemporal Distribution of Natural and Anthropogenic Processes on River Water-Quality Variation Using a Self-Organizing Map With Factor Analysis.

PubMed

Wang, Yeuh-Bin; Liu, Chen-Wuing; Lee, Jin-Jing

2015-08-01

To elucidate the historical improvement and advanced measure of river water quality in the Taipei metropolitan area, this study applied the self-organizing map (SOM) technique with factor analysis (FA) to differentiate the spatiotemporal distribution of natural and anthropogenic processes on river water-quality variation spanning two decades. The SOM clustered river water quality into five groups: very low pollution, low pollution, moderate pollution, high pollution, and very high pollution. FA was then used to extract four latent factors that dominated water quality from 1991 to 2011 including three anthropogenic process factors (organic, industrial, and copper pollution) and one natural process factor [suspended solids (SS) pollution]. The SOM revealed that the water quality improved substantially over time. However, the downstream river water quality was still classified as high pollution because of an increase in anthropogenic activity. FA showed the spatiotemporal pattern of each factor score decreasing over time, but the organic pollution factor downstream of the Tamsui River, as well as the SS factor scores in the upstream major tributary (the Dahan Stream), remained within the high pollution level. Therefore, we suggest that public sewage-treatment plants should be upgraded from their current secondary biological processing to advanced treatment processing. The conservation of water and soil must also be reinforced to decrease the SS loading of the Dahan Stream from natural erosion processes in the future.

A Social–Ecological, Process-Oriented Perspective on Political Violence and Child Development

PubMed Central

Cummings, E. Mark; Goeke-Morey, Marcie; Merrilees, Christine E.; Taylor, Laura K.; Shirlow, Peter A.

2015-01-01

Youths’ risk for adjustment problems in contexts of political violence is well-documented. However, outcomes vary widely, with many children functioning well. Accordingly, moving beyond further documenting the risk for many negative outcomes associated with living in contexts of political violence, a second generation of research is moving towards identifying the mechanisms and conditions that contribute to children’s adjustment. Increasing support is emerging for understanding effects on children in terms of changes in the social contexts in which children live, and in the psychological processes engaged by these social ecologies. Selected themes are considered, including (a) the need to study multiple levels of the social ecology, (b) differentiating between the effects of exposure to contexts of political versus non-political violence, and (c) theories about explanatory processes. Selected research pertinent to these directions is reviewed, including findings from a six-wave longitudinal study on political violence and children in Northern Ireland. PMID:26877765

A Social-Ecological, Process-Oriented Perspective on Political Violence and Child Development.

PubMed

Cummings, E Mark; Goeke-Morey, Marcie; Merrilees, Christine E; Taylor, Laura K; Shirlow, Peter A

2014-06-01

Youths' risk for adjustment problems in contexts of political violence is well-documented. However, outcomes vary widely, with many children functioning well. Accordingly, moving beyond further documenting the risk for many negative outcomes associated with living in contexts of political violence, a second generation of research is moving towards identifying the mechanisms and conditions that contribute to children's adjustment. Increasing support is emerging for understanding effects on children in terms of changes in the social contexts in which children live, and in the psychological processes engaged by these social ecologies. Selected themes are considered, including (a) the need to study multiple levels of the social ecology, (b) differentiating between the effects of exposure to contexts of political versus non-political violence, and (c) theories about explanatory processes. Selected research pertinent to these directions is reviewed, including findings from a six-wave longitudinal study on political violence and children in Northern Ireland.

Interhemispheric Connectivity Influences the Degree of Modulation of TMS-Induced Effects during Auditory Processing

PubMed Central

Andoh, Jamila; Zatorre, Robert J.

2011-01-01

Repetitive transcranial magnetic stimulation (rTMS) has been shown to interfere with many components of language processing, including semantic, syntactic, and phonologic. However, not much is known about its effects on nonlinguistic auditory processing, especially its action on Heschl's gyrus (HG). We aimed to investigate the behavioral and neural basis of rTMS during a melody processing task, while targeting the left HG, the right HG, and the Vertex as a control site. Response times (RT) were normalized relative to the baseline-rTMS (Vertex) and expressed as percentage change from baseline (%RT change). We also looked at sex differences in rTMS-induced response as well as in functional connectivity during melody processing using rTMS and functional magnetic resonance imaging (fMRI). fMRI results showed an increase in the right HG compared with the left HG during the melody task, as well as sex differences in functional connectivity indicating a greater interhemispheric connectivity between left and right HG in females compared with males. TMS results showed that 10 Hz-rTMS targeting the right HG induced differential effects according to sex, with a facilitation of performance in females and an impairment of performance in males. We also found a differential correlation between the %RT change after 10 Hz-rTMS targeting the right HG and the interhemispheric functional connectivity between right and left HG, indicating that an increase in interhemispheric functional connectivity was associated with a facilitation of performance. This is the first study to report a differential rTMS-induced interference with melody processing depending on sex. In addition, we showed a relationship between the interference induced by rTMS on behavioral performance and the neural activity in the network connecting left and right HG, suggesting that the interhemispheric functional connectivity could determine the degree of modulation of behavioral performance. PMID:21811478

Proteomes of the Female Genital Tract During the Oestrous Cycle*

PubMed Central

Soleilhavoup, Clement; Riou, Cindy; Tsikis, Guillaume; Labas, Valerie; Harichaux, Gregoire; Kohnke, Philippa; Reynaud, Karine; de Graaf, Simon P.; Gerard, Nadine; Druart, Xavier

2016-01-01

The female genital tract includes several anatomical regions whose luminal fluids successively interact with gametes and embryos and are involved in the fertilisation and development processes. The luminal fluids from the inner cervix, the uterus and the oviduct were collected along the oestrous cycle at oestrus (Day 0 of the cycle) and during the luteal phase (Day 10) from adult cyclic ewes. The proteomes were assessed by GeLC-MS/MS and quantified by spectral counting. A set of 940 proteins were identified including 291 proteins differentially present along the cycle in one or several regions. The global analysis of the fluid proteomes revealed a general pattern of endocrine regulation of the tract, with the cervix and the oviduct showing an increased differential proteins abundance mainly at oestrus while the uterus showed an increased abundance mainly during the luteal phase. The proteins more abundant at oestrus included several families such as the heat shock proteins (HSP), the mucins, the complement cascade proteins and several redox enzymes. Other proteins known for their interaction with gametes such as oviductin (OVGP), osteopontin, HSPA8, and the spermadhesin AWN were also overexpressed at oestrus. The proteins more abundant during the luteal phase were associated with the immune system such as ceruloplasmin, lactoferrin, DMBT1, or PIGR, and also with tissue remodeling such as galectin 3 binding protein, alkaline phosphatase, CD9, or fibulin. Several proteins differentially abundant between estrus and the luteal phase, such as myosin 9 and fibronectin, were also validated by immunohistochemistry. The potential roles in sperm transit and uterine receptivity of the proteins differentially regulated along the cycle in the female genital tract are discussed. PMID:26518761

Proteomes of the Female Genital Tract During the Oestrous Cycle.

PubMed

Soleilhavoup, Clement; Riou, Cindy; Tsikis, Guillaume; Labas, Valerie; Harichaux, Gregoire; Kohnke, Philippa; Reynaud, Karine; de Graaf, Simon P; Gerard, Nadine; Druart, Xavier

2016-01-01

The female genital tract includes several anatomical regions whose luminal fluids successively interact with gametes and embryos and are involved in the fertilisation and development processes. The luminal fluids from the inner cervix, the uterus and the oviduct were collected along the oestrous cycle at oestrus (Day 0 of the cycle) and during the luteal phase (Day 10) from adult cyclic ewes. The proteomes were assessed by GeLC-MS/MS and quantified by spectral counting. A set of 940 proteins were identified including 291 proteins differentially present along the cycle in one or several regions. The global analysis of the fluid proteomes revealed a general pattern of endocrine regulation of the tract, with the cervix and the oviduct showing an increased differential proteins abundance mainly at oestrus while the uterus showed an increased abundance mainly during the luteal phase. The proteins more abundant at oestrus included several families such as the heat shock proteins (HSP), the mucins, the complement cascade proteins and several redox enzymes. Other proteins known for their interaction with gametes such as oviductin (OVGP), osteopontin, HSPA8, and the spermadhesin AWN were also overexpressed at oestrus. The proteins more abundant during the luteal phase were associated with the immune system such as ceruloplasmin, lactoferrin, DMBT1, or PIGR, and also with tissue remodeling such as galectin 3 binding protein, alkaline phosphatase, CD9, or fibulin. Several proteins differentially abundant between estrus and the luteal phase, such as myosin 9 and fibronectin, were also validated by immunohistochemistry. The potential roles in sperm transit and uterine receptivity of the proteins differentially regulated along the cycle in the female genital tract are discussed. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Transcriptome analysis of functional differentiation between haploid and diploid cells of Emiliania huxleyi, a globally significant photosynthetic calcifying cell.

PubMed

von Dassow, Peter; Ogata, Hiroyuki; Probert, Ian; Wincker, Patrick; Da Silva, Corinne; Audic, Stéphane; Claverie, Jean-Michel; de Vargas, Colomban

2009-01-01

Eukaryotes are classified as either haplontic, diplontic, or haplo-diplontic, depending on which ploidy levels undergo mitotic cell division in the life cycle. Emiliania huxleyi is one of the most abundant phytoplankton species in the ocean, playing an important role in global carbon fluxes, and represents haptophytes, an enigmatic group of unicellular organisms that diverged early in eukaryotic evolution. This species is haplo-diplontic. Little is known about the haploid cells, but they have been hypothesized to allow persistence of the species between the yearly blooms of diploid cells. We sequenced over 38,000 expressed sequence tags from haploid and diploid E. huxleyi normalized cDNA libraries to identify genes involved in important processes specific to each life phase (2N calcification or 1N motility), and to better understand the haploid phase of this prominent haplo-diplontic organism. The haploid and diploid transcriptomes showed a dramatic differentiation, with approximately 20% greater transcriptome richness in diploid cells than in haploid cells and only

Transcriptome analysis of functional differentiation between haploid and diploid cells of Emiliania huxleyi, a globally significant photosynthetic calcifying cell

PubMed Central

2009-01-01

Background Eukaryotes are classified as either haplontic, diplontic, or haplo-diplontic, depending on which ploidy levels undergo mitotic cell division in the life cycle. Emiliania huxleyi is one of the most abundant phytoplankton species in the ocean, playing an important role in global carbon fluxes, and represents haptophytes, an enigmatic group of unicellular organisms that diverged early in eukaryotic evolution. This species is haplo-diplontic. Little is known about the haploid cells, but they have been hypothesized to allow persistence of the species between the yearly blooms of diploid cells. We sequenced over 38,000 expressed sequence tags from haploid and diploid E. huxleyi normalized cDNA libraries to identify genes involved in important processes specific to each life phase (2N calcification or 1N motility), and to better understand the haploid phase of this prominent haplo-diplontic organism. Results The haploid and diploid transcriptomes showed a dramatic differentiation, with approximately 20% greater transcriptome richness in diploid cells than in haploid cells and only ≤ 50% of transcripts estimated to be common between the two phases. The major functional category of transcripts differentiating haploids included signal transduction and motility genes. Diploid-specific transcripts included Ca2+, H+, and HCO3- pumps. Potential factors differentiating the transcriptomes included haploid-specific Myb transcription factor homologs and an unusual diploid-specific histone H4 homolog. Conclusions This study permitted the identification of genes likely involved in diploid-specific biomineralization, haploid-specific motility, and transcriptional control. Greater transcriptome richness in diploid cells suggests they may be more versatile for exploiting a diversity of rich environments whereas haploid cells are intrinsically more streamlined. PMID:19832986

Time-ordered product expansions for computational stochastic system biology.

PubMed

Mjolsness, Eric

2013-06-01

The time-ordered product framework of quantum field theory can also be used to understand salient phenomena in stochastic biochemical networks. It is used here to derive Gillespie's stochastic simulation algorithm (SSA) for chemical reaction networks; consequently, the SSA can be interpreted in terms of Feynman diagrams. It is also used here to derive other, more general simulation and parameter-learning algorithms including simulation algorithms for networks of stochastic reaction-like processes operating on parameterized objects, and also hybrid stochastic reaction/differential equation models in which systems of ordinary differential equations evolve the parameters of objects that can also undergo stochastic reactions. Thus, the time-ordered product expansion can be used systematically to derive simulation and parameter-fitting algorithms for stochastic systems.

Homeobox gene distal-less is required for neuronal differentiation and neurite outgrowth in the Drosophila olfactory system

PubMed Central

Plavicki, Jessica; Mader, Sara; Pueschel, Eric; Peebles, Patrick; Boekhoff-Falk, Grace

2012-01-01

Vertebrate Dlx genes have been implicated in the differentiation of multiple neuronal subtypes, including cortical GABAergic interneurons, and mutations in Dlx genes have been linked to clinical conditions such as epilepsy and autism. Here we show that the single Drosophila Dlx homolog, distal-less, is required both to specify chemosensory neurons and to regulate the morphologies of their axons and dendrites. We establish that distal-less is necessary for development of the mushroom body, a brain region that processes olfactory information. These are important examples of distal-less function in an invertebrate nervous system and demonstrate that the Drosophila larval olfactory system is a powerful model in which to understand distal-less functions during neurogenesis. PMID:22307614

On-line transmission electron microscopic image analysis of chromatin texture for differentiation of thyroid gland tumors.

PubMed

Kriete, A; Schäffer, R; Harms, H; Aus, H M

1987-06-01

Nuclei of the cells from the thyroid gland were analyzed in a transmission electron microscope by direct TV scanning and on-line image processing. The method uses the advantages of a visual-perception model to detect structures in noisy and low-contrast images. The features analyzed include area, a form factor and texture parameters from the second derivative stage. Three tumor-free thyroid tissues, three follicular adenomas, three follicular carcinomas and three papillary carcinomas were studied. The computer-aided cytophotometric method showed that the most significant differences were the statistics of the chromatin texture features of homogeneity and regularity. These findings document the possibility of an automated differentiation of tumors at the ultrastructural level.

Negative tunnel magnetoresistance and differential conductance in transport through double quantum dots

NASA Astrophysics Data System (ADS)

Trocha, Piotr; Weymann, Ireneusz; Barnaś, Józef

2009-10-01

Spin-dependent transport through two coupled single-level quantum dots weakly connected to ferromagnetic leads with collinear magnetizations is considered theoretically. Transport characteristics, including the current, linear and nonlinear conductances, and tunnel magnetoresistance are calculated using the real-time diagrammatic technique in the parallel, serial, and intermediate geometries. The effects due to virtual tunneling processes between the two dots via the leads, associated with off-diagonal coupling matrix elements, are also considered. Negative differential conductance and negative tunnel magnetoresistance have been found in the case of serial and intermediate geometries, while no such behavior has been observed for double quantum dots coupled in parallel. It is also shown that transport characteristics strongly depend on the magnitude of the off-diagonal coupling matrix elements.

The regulation of autophagy differentially affects Trypanosoma cruzi metacyclogenesis.

PubMed

Vanrell, María Cristina; Losinno, Antonella Denisse; Cueto, Juan Agustín; Balcazar, Darío; Fraccaroli, Laura Virginia; Carrillo, Carolina; Romano, Patricia Silvia

2017-11-01

Autophagy is a cellular process required for the removal of aged organelles and cytosolic components through lysosomal degradation. All types of eukaryotic cells from yeasts to mammalian cells have the machinery to activate autophagy as a result of many physiological and pathological situations. The most frequent stimulus of autophagy is starvation and the result, in this case, is the fast generation of utilizable food (e.g. amino acids and basic nutrients) to maintain the vital biological processes. In some organisms, starvation also triggers other associated processes such as differentiation. The protozoan parasite Trypanosoma cruzi undergoes a series of differentiation processes throughout its complex life cycle. Although not all autophagic genes have been identified in the T. cruzi genome, previous works have demonstrated the presence of essential autophagic-related proteins. Under starvation conditions, TcAtg8, which is the parasite homolog of Atg8/LC3 in other organisms, is located in autophagosome-like vesicles. In this work, we have characterized the autophagic pathway during T. cruzi differentiation from the epimastigote to metacyclic trypomastigote form, a process called metacyclogenesis. We demonstrated that autophagy is stimulated during metacyclogenesis and that the induction of autophagy promotes this process. Moreover, with exception of bafilomycin, other classical autophagy modulators have similar effects on T. cruzi autophagy. We also showed that spermidine and related polyamines can positively regulate parasite autophagy and differentiation. We concluded that both polyamine metabolism and autophagy are key processes during T. cruzi metacyclogenesis that could be exploited as drug targets to avoid the parasite cycle progression.

Differential fluorescence EEMs can be used to assess treatability of DOM during drinking water production

NASA Astrophysics Data System (ADS)

Lavonen, Elin; Kothawala, Dolly; Tranvik, Lars; Köhler, Stephan

2014-05-01

Fluorescence spectroscopy has been widely used to characterize fluorescent dissolved organic matter (FDOM) in various waters including during drinking water production. Commonly used techniques for data treatment include peak picking, indexes calculated from 2D emission spectra and modelling of fluorescence components using parallel factor analysis (PARAFAC). However, peak picking and indexes only use limited information from the fluorescence EEMs and PARAFAC requires a larger dataset and experience to perform. Because DOM is a major issue in drinking water production, and personnel at water treatment plants usually have limited time for advanced analysis we have developed a simple way of assessing the treatability of DOM in different waters using differential fluorescence. With this approach the removed fraction of FDOM is calculated from samples taken before and after a particular treatment process and the percentage of removed material assessed. Samples have been collected from four large water treatment plants in Sweden and analyzed for 3Dfluorescence, absorbance and DOC. The selective removal of DOM during e.g. flocculation and slow sand filtration as well as differences in experienced treatability between the treatment plants was described with differential fluorescence. Chemical flocculation is selective towards FDOM with red-shifted emission across the entire EEM. Red-shift has earlier been connected to condensation (i.e. decrease in H/C) and positively correlated to molecular size indicating that larger, humified molecules are being preferentially removed. During the biological process of slow sand filtration compounds with blue-shifted emission are targeted demonstrating selective removal of more freshly produced, microbial material. Disinfection with UV/NH2Cl and NaOCl was found to only target material with protein-like fluorescence suggesting that FDOM of this nature could be responsible for unwanted consumption of disinfection agent. Targeted removal of this fraction prior to disinfection should optimize the process. Furthermore, the main process at all studied WTPs is flocculation and their experienced treatability could easily be explained through the percentage of FDOM with emission above 450 nm (p<0.0001).

An estimator for the relative entropy rate of path measures for stochastic differential equations

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

Opper, Manfred, E-mail: manfred.opper@tu-berlin.de

2017-02-01

We address the problem of estimating the relative entropy rate (RER) for two stochastic processes described by stochastic differential equations. For the case where the drift of one process is known analytically, but one has only observations from the second process, we use a variational bound on the RER to construct an estimator.

CCK processing by pituitary GH3 cells, human teratocarcinoma cells NT2 and hNT differentiated human neuronal cells evidence for a differentiation-induced change in enzyme expression and pro CCK processing.

PubMed

Beinfeld, Margery C; Wang, Wenge

2002-02-01

Human teratocarcinoma Ntera2/c 1.D1 (NT2) cells express very low levels of the prohormone convertase enzyme PC1, moderate levels of PC2 and significant levels of PC5. When infected with an adenovirus which expresses rat CCK mRNA, several glycine-extended forms were secreted that co-eluted with CCK 33, 22 and 12. Amidated CCK is not produced because these cells appear to lack the amidating enzyme. Pituitary GH3 cells express high levels of PC2 and PC5. CCK adenovirus-infected GH3 cells secrete amidated versions of the same peptides as NT2 cells. Differentiation of NT2 cells into hNT cells with retinoic acid and mitotic inhibitors increased expression of PC5 and decreased expression of PCI and PC2. CCK adenovirus-infected differentiated hNT cells also secrete glycine extended CCK products and the major molecular form produced co-eluted with CCK 8 Gly. These experiments demonstrate that the state of differentiation of this neuronal cell line influences its expression of PC 1,2, and 5 and its cleavage of pro CCK and suggests that these cells may make an interesting model to study how differentiation alters prohormone processing. These results also support the hypothesis that PC5 in differentiated neuronal cells is capable of processing pro CCK to glycine-extended CCK 8.

Coupled Nd-142, Nd-143 and Hf-176 Isotopic Data from 3.6-3.9 Ga Rocks: New Constraints on the Timing of Early Terrestrial Chemical Reservoirs

NASA Technical Reports Server (NTRS)

Bennett, Vickie C.; Brandon, alan D.; Hiess, Joe; Nutman, Allen P.

2007-01-01

Increasingly precise data from a range of isotopic decay schemes, including now extinct parent isotopes, from samples of the Earth, Mars, Moon and meteorites are rapidly revising our views of early planetary differentiation. Recognising Nd-142 isotopic variations in terrestrial rocks (which can only arise from events occurring during the lifetime of now extinct Sm-146 [t(sub 1/2)=103 myr]) has been an on-going quest starting with Harper and Jacobsen. The significance of Nd-142 variations is that they unequivocally reflect early silicate differentiation processes operating in the first 500 myr of Earth history, the key time period between accretion and the beginning of the rock record. The recent establishment of the existence of Nd-142 variations in ancient Earth materials has opened a new range of questions including, how widespread is the evidence of early differentiation, how do Nd-142 compositions vary with time, rock type and geographic setting, and, combined with other types of isotopic and geochemical data, what can Nd-142 isotopic variations reveal about the timing and mechanisms of early terrestrial differentiation? To explore these questions we are determining high precision Nd-142, Nd-143 and Hf-176 isotopic compositions from the oldest well preserved (3.63- 3.87 Ga), rock suites from the extensive early Archean terranes of southwest Greenland and western Australia.

The emerging role of Hippo signaling pathway in regulating osteoclast formation.

PubMed

Yang, Wanlei; Han, Weiqi; Qin, An; Wang, Ziyi; Xu, Jiake; Qian, Yu

2018-06-01

A delicate balance between osteoblastic bone formation and osteoclastic bone resorption is crucial for bone homeostasis. This process is regulated by the Hippo signaling pathway including key regulatory molecules RASSF2, NF2, MST1/2, SAV1, LATS1/2, MOB1, YAP, and TAZ. It is well established that the Hippo signaling pathway plays an important part in regulating osteoblast differentiation, but its role in osteoclast formation and activation remains poorly understood. In this review, we discuss the emerging role of Hippo-signaling pathway in osteoclast formation and bone homeostasis. It is revealed that specific molecules of the Hippo-signaling pathway take part in a stage specific regulation in pre-osteoclast proliferation, osteoclast differentiation and osteoclast apoptosis and survival. Upon activation, MST and LAST, transcriptional co-activators YAP and TAZ bind to the members of the TEA domain (TEAD) family transcription factors, and influence osteoclast differentiation via regulating the expression of downstream target genes such as connective tissue growth factor (CTGF/CCN2) and cysteine-rich protein 61 (CYR61/CCN1). In addition, through interacting or cross talking with RANKL-mediated signaling cascades including NF-κB, MAPKs, AP1, and NFATc1, Hippo-signaling molecules such as YAP/TAZ/TEAD complex, RASSF2, MST2, and Ajuba could also potentially modulate osteoclast differentiation and function. Elucidating the roles of the Hippo-signaling pathway in osteoclast development and specific molecules involved is important for understanding the mechanism of bone homeostasis and diseases. © 2017 Wiley Periodicals, Inc.

An fMRI study on the comparison of different types of false belief reasoning: False belief-based emotion and behavior attribution.

PubMed

Döhnel, Katrin; Schuwerk, Tobias; Sodian, Beate; Hajak, Göran; Rupprecht, Rainer; Sommer, Monika

2017-12-01

False belief (FB) reasoning is a key Theory of Mind (ToM) competence. By 4 years of age, children understand that a person's behavior can be based on a FB about reality. Children cannot understand that a person's emotion can also be based on a FB before the age of six. In order to generate hypothesis on basic processes distinguishing these two types of belief reasoning, the present functional magnetic resonance imaging study in adults directly compares functional activity associated with these two FB tasks. Both tasks were associated with activity in the ToM network including the medial prefrontal cortex and the left temporo-parietal junction. Differential activity was observed in the anterior dorsolateral prefrontal cortex for FB-based emotion relative to behavior attribution. Contrary to FB behavior attribution, FB-based emotion attribution requires the processing of two different mental states: a belief and an emotion and their relation to each other. The activity pattern may reflect the differential demands on cognitive processes associated with the two different belief-based attribution processes. These results shed new light on the still ongoing debate about the nature of the developmental lag between the two FB tasks.

Yeast cell differentiation: Lessons from pathogenic and non-pathogenic yeasts.

PubMed

Palková, Zdena; Váchová, Libuše

2016-09-01

Yeasts, historically considered to be single-cell organisms, are able to activate different differentiation processes. Individual yeast cells can change their life-styles by processes of phenotypic switching such as the switch from yeast-shaped cells to filamentous cells (pseudohyphae or true hyphae) and the transition among opaque, white and gray cell-types. Yeasts can also create organized multicellular structures such as colonies and biofilms, and the latter are often observed as contaminants on surfaces in industry and medical care and are formed during infections of the human body. Multicellular structures are formed mostly of stationary-phase or slow-growing cells that diversify into specific cell subpopulations that have unique metabolic properties and can fulfill specific tasks. In addition to the development of multiple protective mechanisms, processes of metabolic reprogramming that reflect a changed environment help differentiated individual cells and/or community cell constituents to survive harmful environmental attacks and/or to escape the host immune system. This review aims to provide an overview of differentiation processes so far identified in individual yeast cells as well as in multicellular communities of yeast pathogens of the Candida and Cryptococcus spp. and the Candida albicans close relative, Saccharomyces cerevisiae. Molecular mechanisms and extracellular signals potentially involved in differentiation processes are also briefly mentioned. Copyright © 2016 Elsevier Ltd. All rights reserved.

Optimal segmentation and packaging process

DOEpatents

Kostelnik, K.M.; Meservey, R.H.; Landon, M.D.

1999-08-10

A process for improving packaging efficiency uses three dimensional, computer simulated models with various optimization algorithms to determine the optimal segmentation process and packaging configurations based on constraints including container limitations. The present invention is applied to a process for decontaminating, decommissioning (D and D), and remediating a nuclear facility involving the segmentation and packaging of contaminated items in waste containers in order to minimize the number of cuts, maximize packaging density, and reduce worker radiation exposure. A three-dimensional, computer simulated, facility model of the contaminated items are created. The contaminated items are differentiated. The optimal location, orientation and sequence of the segmentation and packaging of the contaminated items is determined using the simulated model, the algorithms, and various constraints including container limitations. The cut locations and orientations are transposed to the simulated model. The contaminated items are actually segmented and packaged. The segmentation and packaging may be simulated beforehand. In addition, the contaminated items may be cataloged and recorded. 3 figs.

Intrinsic Deregulation of Vascular Smooth Muscle and Myofibroblast Differentiation in Mesenchymal Stromal Cells from Patients with Systemic Sclerosis.

PubMed

Hegner, Björn; Schaub, Theres; Catar, Rusan; Kusch, Angelika; Wagner, Philine; Essin, Kirill; Lange, Claudia; Riemekasten, Gabriela; Dragun, Duska

2016-01-01

Obliterative vasculopathy and fibrosis are hallmarks of systemic sclerosis (SSc), a severe systemic autoimmune disease. Bone marrow-derived mesenchymal stromal cells (MSCs) from SSc patients may harbor disease-specific abnormalities. We hypothesized disturbed vascular smooth muscle cell (VSMC) differentiation with increased propensity towards myofibroblast differentiation in response to SSc-microenvironment defining growth factors and determined responsible mechanisms. We studied responses of multipotent MSCs from SSc-patients (SSc-MSCs) and healthy controls (H-MSCs) to long-term exposure to CTGF, b-FGF, PDGF-BB or TGF-β1. Differentiation towards VSMC and myofibroblast lineages was analyzed on phenotypic, biochemical, and functional levels. Intracellular signaling studies included analysis of TGF-β receptor regulation, SMAD, AKT, ERK1/2 and autocrine loops. VSMC differentiation towards both, contractile and synthetic VSMC phenotypes in response to CTGF and b-FGF was disturbed in SSc-MSCs. H-MSCs and SSc-MSCs responded equally to PDGF-BB with prototypic fibroblastic differentiation. TGF-β1 initiated myofibroblast differentiation in both cell types, yet with striking phenotypic and functional differences: In relation to H-MSC-derived myofibroblasts induced by TGF-β1, those obtained from SSc-MSCs expressed more contractile proteins, migrated towards TGF-β1, had low proliferative capacity, and secreted higher amounts of collagen paralleled by reduced MMP expression. Higher levels of TGF-β receptor 1 and enhanced canonical and noncanonical TGF-β signaling in SSc-MSCs accompanied aberrant differentiation response of SSc-MSCs in comparison to H-MSCs. Deregulated VSMC differentiation with a shift towards myofibroblast differentiation expands the concept of disturbed endogenous regenerative capacity of MSCs from SSc patients. Disease related intrinsic hyperresponsiveness to TGF-β1 with increased collagen production may represent one responsible mechanism. Better understanding of repair barriers and harnessing beneficial differentiation processes in MSCs could widen options of autologous MSC application in SSc patients.

Induction of CD4 T cell memory by local cellular collectivity.

PubMed

Polonsky, Michal; Rimer, Jacob; Kern-Perets, Amos; Zaretsky, Irina; Miller, Stav; Bornstein, Chamutal; David, Eyal; Kopelman, Naama Meira; Stelzer, Gil; Porat, Ziv; Chain, Benjamin; Friedman, Nir

2018-06-15

Cell differentiation is directed by signals driving progenitors into specialized cell types. This process can involve collective decision-making, when differentiating cells determine their lineage choice by interacting with each other. We used live-cell imaging in microwell arrays to study collective processes affecting differentiation of naïve CD4 + T cells into memory precursors. We found that differentiation of precursor memory T cells sharply increases above a threshold number of locally interacting cells. These homotypic interactions involve the cytokines interleukin-2 (IL-2) and IL-6, which affect memory differentiation orthogonal to their effect on proliferation and survival. Mathematical modeling suggests that the differentiation rate is continuously modulated by the instantaneous number of locally interacting cells. This cellular collectivity can prioritize allocation of immune memory to stronger responses. Copyright © 2018, American Association for the Advancement of Science.

The Conjugation-Specific Die5 Protein Is Required for Development of the Somatic Nucleus in both Paramecium and Tetrahymena▿

PubMed Central

Matsuda, Atsushi; Shieh, Annie Wan-Yi; Chalker, Douglas L.; Forney, James D.

2010-01-01

Development in ciliated protozoa involves extensive genome reorganization within differentiating macronuclei, which shapes the somatic genome of the next vegetative generation. Major events of macronuclear differentiation include excision of internal eliminated sequences (IESs), chromosome fragmentation, and genome amplification. Proteins required for these events include those with homology throughout eukaryotes as well as proteins apparently unique to ciliates. In this study, we identified the ciliate-specific Defective in IES Excision 5 (DIE5) genes of Paramecium tetraurelia (PtDIE5) and Tetrahymena thermophila (TtDIE5) as orthologs that encode nuclear proteins expressed exclusively during development. Abrogation of PtDie5 protein (PtDie5p) function by RNA interference (RNAi)-mediated silencing or TtDie5p by gene disruption resulted in the failure of developing macronuclei to differentiate into new somatic nuclei. Tetrahymena ΔDIE5 cells arrested late in development and failed to complete genome amplification, whereas RNAi-treated Paramecium cells highly amplified new macronuclear DNA before the failure in differentiation, findings that highlight clear differences in the biology of these distantly related species. Nevertheless, IES excision and chromosome fragmentation failed to occur in either ciliate, which strongly supports that Die5p is a critical player in these processes. In Tetrahymena, loss of zygotic expression during development was sufficient to block nuclear differentiation. This observation, together with the finding that knockdown of Die5p in Paramecium still allows genome amplification, indicates that this protein acts late in macronuclear development. Even though DNA rearrangements in these two ciliates look to be quite distinct, analysis of DIE5 establishes the action of a conserved mechanism within the genome reorganization pathway. PMID:20495055

The conjugation-specific Die5 protein is required for development of the somatic nucleus in both Paramecium and Tetrahymena.

PubMed

Matsuda, Atsushi; Shieh, Annie Wan-Yi; Chalker, Douglas L; Forney, James D

2010-07-01

Development in ciliated protozoa involves extensive genome reorganization within differentiating macronuclei, which shapes the somatic genome of the next vegetative generation. Major events of macronuclear differentiation include excision of internal eliminated sequences (IESs), chromosome fragmentation, and genome amplification. Proteins required for these events include those with homology throughout eukaryotes as well as proteins apparently unique to ciliates. In this study, we identified the ciliate-specific Defective in IES Excision 5 (DIE5) genes of Paramecium tetraurelia (PtDIE5) and Tetrahymena thermophila (TtDIE5) as orthologs that encode nuclear proteins expressed exclusively during development. Abrogation of PtDie5 protein (PtDie5p) function by RNA interference (RNAi)-mediated silencing or TtDie5p by gene disruption resulted in the failure of developing macronuclei to differentiate into new somatic nuclei. Tetrahymena DeltaDIE5 cells arrested late in development and failed to complete genome amplification, whereas RNAi-treated Paramecium cells highly amplified new macronuclear DNA before the failure in differentiation, findings that highlight clear differences in the biology of these distantly related species. Nevertheless, IES excision and chromosome fragmentation failed to occur in either ciliate, which strongly supports that Die5p is a critical player in these processes. In Tetrahymena, loss of zygotic expression during development was sufficient to block nuclear differentiation. This observation, together with the finding that knockdown of Die5p in Paramecium still allows genome amplification, indicates that this protein acts late in macronuclear development. Even though DNA rearrangements in these two ciliates look to be quite distinct, analysis of DIE5 establishes the action of a conserved mechanism within the genome reorganization pathway.

Osteoblast Differentiation and Bone Matrix Formation In Vivo and In Vitro.

PubMed

Blair, Harry C; Larrouture, Quitterie C; Li, Yanan; Lin, Hang; Beer-Stoltz, Donna; Liu, Li; Tuan, Rocky S; Robinson, Lisa J; Schlesinger, Paul H; Nelson, Deborah J

2017-06-01

We review the characteristics of osteoblast differentiation and bone matrix synthesis. Bone in air breathing vertebrates is a specialized tissue that developmentally replaces simpler solid tissues, usually cartilage. Bone is a living organ bounded by a layer of osteoblasts that, because of transport and compartmentalization requirements, produce bone matrix exclusively as an organized tight epithelium. With matrix growth, osteoblasts are reorganized and incorporated into the matrix as living cells, osteocytes, which communicate with each other and surface epithelium by cell processes within canaliculi in the matrix. The osteoblasts secrete the organic matrix, which are dense collagen layers that alternate parallel and orthogonal to the axis of stress loading. Into this matrix is deposited extremely dense hydroxyapatite-based mineral driven by both active and passive transport and pH control. As the matrix matures, hydroxyapatite microcrystals are organized into a sophisticated composite in the collagen layer by nucleation in the protein lattice. Recent studies on differentiating osteoblast precursors revealed a sophisticated proton export network driving mineralization, a gene expression program organized with the compartmentalization of the osteoblast epithelium that produces the mature bone matrix composite, despite varying serum calcium and phosphate. Key issues not well defined include how new osteoblasts are incorporated in the epithelial layer, replacing those incorporated in the accumulating matrix. Development of bone in vitro is the subject of numerous projects using various matrices and mesenchymal stem cell-derived preparations in bioreactors. These preparations reflect the structure of bone to variable extents, and include cells at many different stages of differentiation. Major challenges are production of bone matrix approaching the in vivo density and support for trabecular bone formation. In vitro differentiation is limited by the organization and density of osteoblasts and by endogenous and exogenous inhibitors.

Osteoblast Differentiation and Bone Matrix Formation In Vivo and In Vitro

PubMed Central

Larrouture, Quitterie C.; Li, Yanan; Lin, Hang; Beer-Stoltz, Donna; Liu, Li; Tuan, Rocky S.; Robinson, Lisa J.; Schlesinger, Paul H.; Nelson, Deborah J.

2017-01-01

We review the characteristics of osteoblast differentiation and bone matrix synthesis. Bone in air breathing vertebrates is a specialized tissue that developmentally replaces simpler solid tissues, usually cartilage. Bone is a living organ bounded by a layer of osteoblasts that, because of transport and compartmentalization requirements, produce bone matrix exclusively as an organized tight epithelium. With matrix growth, osteoblasts are reorganized and incorporated into the matrix as living cells, osteocytes, which communicate with each other and surface epithelium by cell processes within canaliculi in the matrix. The osteoblasts secrete the organic matrix, which are dense collagen layers that alternate parallel and orthogonal to the axis of stress loading. Into this matrix is deposited extremely dense hydroxyapatite-based mineral driven by both active and passive transport and pH control. As the matrix matures, hydroxyapatite microcrystals are organized into a sophisticated composite in the collagen layer by nucleation in the protein lattice. Recent studies on differentiating osteoblast precursors revealed a sophisticated proton export network driving mineralization, a gene expression program organized with the compartmentalization of the osteoblast epithelium that produces the mature bone matrix composite, despite varying serum calcium and phosphate. Key issues not well defined include how new osteoblasts are incorporated in the epithelial layer, replacing those incorporated in the accumulating matrix. Development of bone in vitro is the subject of numerous projects using various matrices and mesenchymal stem cell-derived preparations in bioreactors. These preparations reflect the structure of bone to variable extents, and include cells at many different stages of differentiation. Major challenges are production of bone matrix approaching the in vivo density and support for trabecular bone formation. In vitro differentiation is limited by the organization and density of osteoblasts and by endogenous and exogenous inhibitors. PMID:27846781

Bovine mammary gene expression profiling during the onset of lactation.

PubMed

Gao, Yuanyuan; Lin, Xueyan; Shi, Kerong; Yan, Zhengui; Wang, Zhonghua

2013-01-01

Lactogenesis includes two stages. Stage I begins a few weeks before parturition. Stage II is initiated around the time of parturition and extends for several days afterwards. To better understand the molecular events underlying these changes, genome-wide gene expression profiling was conducted using digital gene expression (DGE) on bovine mammary tissue at three time points (on approximately day 35 before parturition (-35 d), day 7 before parturition (-7 d) and day 3 after parturition (+3 d)). Approximately 6.2 million (M), 5.8 million (M) and 6.1 million (M) 21-nt cDNA tags were sequenced in the three cDNA libraries (-35 d, -7 d and +3 d), respectively. After aligning to the reference sequences, the three cDNA libraries included 8,662, 8,363 and 8,359 genes, respectively. With a fold change cutoff criteria of ≥ 2 or ≤-2 and a false discovery rate (FDR) of ≤ 0.001, a total of 812 genes were significantly differentially expressed at -7 d compared with -35 d (stage I). Gene ontology analysis showed that those significantly differentially expressed genes were mainly associated with cell cycle, lipid metabolism, immune response and biological adhesion. A total of 1,189 genes were significantly differentially expressed at +3 d compared with -7 d (stage II), and these genes were mainly associated with the immune response and cell cycle. Moreover, there were 1,672 genes significantly differentially expressed at +3 d compared with -35 d. Gene ontology analysis showed that the main differentially expressed genes were those associated with metabolic processes. The results suggest that the mammary gland begins to lactate not only by a gain of function but also by a broad suppression of function to effectively push most of the cell's resources towards lactation.

Modeling biological gradient formation: combining partial differential equations and Petri nets.

PubMed

Bertens, Laura M F; Kleijn, Jetty; Hille, Sander C; Heiner, Monika; Koutny, Maciej; Verbeek, Fons J

2016-01-01

Both Petri nets and differential equations are important modeling tools for biological processes. In this paper we demonstrate how these two modeling techniques can be combined to describe biological gradient formation. Parameters derived from partial differential equation describing the process of gradient formation are incorporated in an abstract Petri net model. The quantitative aspects of the resulting model are validated through a case study of gradient formation in the fruit fly.

Estimation of nonlinear pilot model parameters including time delay.

NASA Technical Reports Server (NTRS)

Schiess, J. R.; Roland, V. R.; Wells, W. R.

1972-01-01

Investigation of the feasibility of using a Kalman filter estimator for the identification of unknown parameters in nonlinear dynamic systems with a time delay. The problem considered is the application of estimation theory to determine the parameters of a family of pilot models containing delayed states. In particular, the pilot-plant dynamics are described by differential-difference equations of the retarded type. The pilot delay, included as one of the unknown parameters to be determined, is kept in pure form as opposed to the Pade approximations generally used for these systems. Problem areas associated with processing real pilot response data are included in the discussion.

Detection of a concealed object

DOEpatents

Keller, Paul E [Richland, WA; Hall, Thomas E [Kennewick, WA; McMakin, Douglas L [Richland, WA

2010-11-16

Disclosed are systems, methods, devices, and apparatus to determine if a clothed individual is carrying a suspicious, concealed object. This determination includes establishing data corresponding to an image of the individual through interrogation with electromagnetic radiation in the 200 MHz to 1 THz range. In one form, image data corresponding to intensity of reflected radiation and differential depth of the reflecting surface is received and processed to detect the suspicious, concealed object.

Detection of a concealed object

DOEpatents

Keller, Paul E [Richland, WA; Hall, Thomas E [Kennewick, WA; McMakin, Douglas L [Richland, WA

2008-04-29

Disclosed are systems, methods, devices, and apparatus to determine if a clothed individual is carrying a suspicious, concealed object. This determination includes establishing data corresponding to an image of the individual through interrogation with electromagnetic radiation in the 200 MHz to 1 THz range. In one form, image data corresponding to intensity of reflected radiation and differential depth of the reflecting surface is received and processed to detect the suspicious, concealed object.

Members of FOX family could be drug targets of cancers.

PubMed

Wang, Jinhua; Li, Wan; Zhao, Ying; Kang, De; Fu, Weiqi; Zheng, Xiangjin; Pang, Xiaocong; Du, Guanhua

2018-01-01

FOX families play important roles in biological processes, including metabolism, development, differentiation, proliferation, apoptosis, migration, invasion and longevity. Here we are focusing on roles of FOX members in cancers, FOX members and drug resistance, FOX members and stem cells. Finally, FOX members as drug targets of cancer treatment were discussed. Future perspectives of FOXC1 research were described in the end. Copyright © 2017 Elsevier Inc. All rights reserved.

Silicon isotopes in angrites and volatile loss in planetesimals

PubMed Central

Moynier, Frédéric; Savage, Paul S.; Badro, James; Barrat, Jean-Alix

2014-01-01

Inner solar system bodies, including the Earth, Moon, and asteroids, are depleted in volatile elements relative to chondrites. Hypotheses for this volatile element depletion include incomplete condensation from the solar nebula and volatile loss during energetic impacts. These processes are expected to each produce characteristic stable isotope signatures. However, processes of planetary differentiation may also modify the isotopic composition of geochemical reservoirs. Angrites are rare meteorites that crystallized only a few million years after calcium–aluminum-rich inclusions and exhibit extreme depletions in volatile elements relative to chondrites, making them ideal samples with which to study volatile element depletion in the early solar system. Here we present high-precision Si isotope data that show angrites are enriched in the heavy isotopes of Si relative to chondritic meteorites by 50–100 ppm/amu. Silicon is sufficiently volatile such that it may be isotopically fractionated during incomplete condensation or evaporative mass loss, but theoretical calculations and experimental results also predict isotope fractionation under specific conditions of metal–silicate differentiation. We show that the Si isotope composition of angrites cannot be explained by any plausible core formation scenario, but rather reflects isotope fractionation during impact-induced evaporation. Our results indicate planetesimals initially formed from volatile-rich material and were subsequently depleted in volatile elements during accretion. PMID:25404309

Contribution of MAML1 in esophageal squamous cell carcinoma tumorigenesis.

PubMed

Hashemi Bidokhti, Mahnaz; Abbaszadegan, Mohammad Reza; Sharifi, Noorieh; Abbasi Sani, Soodabeh; Forghanifard, Mohammad Mahdi

2017-04-01

Notch signaling pathway is involved in different cellular and developmental processes including cell proliferation, differentiation and apoptosis. Mastermind like1 (MAML1) is a critical key transcription coactivator of this pathway. In this study, we aimed to examine MAML1 protein expression in esophageal squamous cell carcinoma (ESCC) and reveal its association with clinicopathological variables of the patients. Tumoral and their margin normal tissues from 56 ESCC patients were recruited for protein expression analysis using immunohistochemistry (IHC). Furthermore, MAML1 expression was analyzed in ESCC cell line KYSE-30 using immunocytochemistry. Overexpression of MAML1 was detected in 59% of tumor samples. It was significantly associated with different indices of poor prognosis including depth of tumor invasion (P=0.026), grade of tumor differentiation (P=0.002), stage of tumor progression (P=0.004) and sex (P=0.027). Beside the appearing evidences explaining MAML1 role in different cellular processes and its deviations in different malignancies and also based on its correlation with different clinicopathological variables of ESCC, MAML1 can be proposed as potentially novel molecular marker for ESCC progression and tumorigenesis as well as therapeutic target to inhibit and reverse progression and development of the disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Ground penetrating radar and differential global positioning system data collected in April 2016 from Fire Island, New York

USGS Publications Warehouse

Forde, Arnell S.; Bernier, Julie C.; Miselis, Jennifer L.

2018-02-22

Researchers from the U.S. Geological Survey (USGS) conducted a long-term coastal morphologic-change study at Fire Island, New York, prior to and after Hurricane Sandy impacted the area in October 2012. The Fire Island Coastal Change project objectives include understanding the morphologic evolution of the barrier island system on a variety of time scales (months to centuries) and resolving storm-related impacts, post-storm beach response, and recovery. In April 2016, scientists from the USGS St. Petersburg Coastal and Marine Science Center conducted geophysical and sediment sampling surveys on Fire Island to characterize and quantify spatial variability in the subaerial geology with the goal of subsequently integrating onshore geology with other surf zone and nearshore datasets.  This report, along with the associated USGS data release, serves as an archive of ground penetrating radar (GPR) and post-processed differential global positioning system (DGPS) data collected from beach and back-barrier environments on Fire Island, April 6–13, 2016 (USGS Field Activity Number 2016-322-FA). Data products, including unprocessed GPR trace data, processed DGPS data, elevation-corrected subsurface profile images, geographic information system files, and accompanying Federal Geographic Data Committee metadata are available for download.

Alternative Polyadenylation in Human Diseases

PubMed Central

Chang, Jae-Woong; Yeh, Hsin-Sung

2017-01-01

Varying length of messenger RNA (mRNA) 3′-untranslated region is generated by alternating the usage of polyadenylation sites during pre-mRNA processing. It is prevalent through all eukaryotes and has emerged as a key mechanism for controlling gene expression. Alternative polyadenylation (APA) plays an important role for cell growth, proliferation, and differentiation. In this review, we discuss the functions of APA related with various physiological conditions including cellular metabolism, mRNA processing, and protein diversity in a variety of disease models. We also discuss the molecular mechanisms underlying APA regulation, such as variations in the concentration of mRNA processing factors and RNA-binding proteins, as well as global transcriptome changes under cellular signaling pathway. PMID:29271615

Differentiating Instruction "in the Regular" Classroom: How To Reach and Teach All Learners, Grades 3-12.

ERIC Educational Resources Information Center

Heacox, Diane

This book provides a wide variety of strategies for differentiating instruction for students in grades 3-12. Chapter 1 presents an overview of differentiated content, process, and product, and the role of the teacher in a differentiated classroom. Chapter 2 focuses on the first step of differentiation: gathering information about students. Chapter…