Overlapping DNA Methylation Dynamics in Mouse Intestinal Cell Differentiation and Early Stages of Malignant Progression

PubMed Central

Forn, Marta; Díez-Villanueva, Anna; Merlos-Suárez, Anna; Muñoz, Mar; Lois, Sergi; Carriò, Elvira; Jordà, Mireia; Bigas, Anna; Batlle, Eduard; Peinado, Miguel A.

2015-01-01

Mouse models of intestinal crypt cell differentiation and tumorigenesis have been used to characterize the molecular mechanisms underlying both processes. DNA methylation is a key epigenetic mark and plays an important role in cell identity and differentiation programs and cancer. To get insights into the dynamics of cell differentiation and malignant transformation we have compared the DNA methylation profiles along the mouse small intestine crypt and early stages of tumorigenesis. Genome-scale analysis of DNA methylation together with microarray gene expression have been applied to compare intestinal crypt stem cells (EphB2high), differentiated cells (EphB2negative), ApcMin/+ adenomas and the corresponding non-tumor adjacent tissue, together with small and large intestine samples and the colon cancer cell line CT26. Compared with late stages, small intestine crypt differentiation and early stages of tumorigenesis display few and relatively small changes in DNA methylation. Hypermethylated loci are largely shared by the two processes and affect the proximities of promoter and enhancer regions, with enrichment in genes associated with the intestinal stem cell signature and the PRC2 complex. The hypermethylation is progressive, with minute levels in differentiated cells, as compared with intestinal stem cells, and reaching full methylation in advanced stages. Hypomethylation shows different signatures in differentiation and cancer and is already present in the non-tumor tissue adjacent to the adenomas in ApcMin/+ mice, but at lower levels than advanced cancers. This study provides a reference framework to decipher the mechanisms driving mouse intestinal tumorigenesis and also the human counterpart. PMID:25933092

Amyloid precursor protein expression and processing are differentially regulated during cortical neuron differentiation.

PubMed

Bergström, Petra; Agholme, Lotta; Nazir, Faisal Hayat; Satir, Tugce Munise; Toombs, Jamie; Wellington, Henrietta; Strandberg, Joakim; Bontell, Thomas Olsson; Kvartsberg, Hlin; Holmström, Maria; Boreström, Cecilia; Simonsson, Stina; Kunath, Tilo; Lindahl, Anders; Blennow, Kaj; Hanse, Eric; Portelius, Erik; Wray, Selina; Zetterberg, Henrik

2016-07-07

Amyloid precursor protein (APP) and its cleavage product amyloid β (Aβ) have been thoroughly studied in Alzheimer's disease. However, APP also appears to be important for neuronal development. Differentiation of induced pluripotent stem cells (iPSCs) towards cortical neurons enables in vitro mechanistic studies on human neuronal development. Here, we investigated expression and proteolytic processing of APP during differentiation of human iPSCs towards cortical neurons over a 100-day period. APP expression remained stable during neuronal differentiation, whereas APP processing changed. α-Cleaved soluble APP (sAPPα) was secreted early during differentiation, from neuronal progenitors, while β-cleaved soluble APP (sAPPβ) was first secreted after deep-layer neurons had formed. Short Aβ peptides, including Aβ1-15/16, peaked during the progenitor stage, while processing shifted towards longer peptides, such as Aβ1-40/42, when post-mitotic neurons appeared. This indicates that APP processing is regulated throughout differentiation of cortical neurons and that amyloidogenic APP processing, as reflected by Aβ1-40/42, is associated with mature neuronal phenotypes.

XBtg2 is required for notochord differentiation during early Xenopus development.

PubMed

Sugimoto, Kaoru; Hayata, Tadayoshi; Asashima, Makoto

2005-09-01

The notochord is essential for normal vertebrate development, serving as both a structural support for the embryo and a signaling source for the patterning of adjacent tissues. Previous studies on the notochord have mostly focused on its formation and function in early organogenesis but gene regulation in the differentiation of notochord cells itself remains poorly defined. In the course of screening for genes expressed in developing notochord, we have isolated Xenopus homolog of Btg2 (XBtg2). The mammalian Btg2 genes, Btg2/PC3/TIS21, have been reported to have multiple functions in the regulation of cell proliferation and differentiation but their roles in early development are still unclear. Here we characterized XBtg2 in early Xenopus laevis embryogenesis with focus on notochord development. Translational inhibition of XBtg2 resulted in a shortened and bent axis phenotype and the abnormal structures in the notochord tissue, which did not undergo vacuolation. The XBtg2-depleted notochord cells expressed early notochord markers such as chordin and Xnot at the early tailbud stage, but failed to express differentiation markers of notochord such as Tor70 and 5-D-4 antigens in the later stages. These results suggest that XBtg2 is required for the differentiation of notochord cells such as the process of vacuolar formation after determination of notochord cell fate.

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.

A zinc finger protein Zfp521 directs neural differentiation and beyond

PubMed Central

2011-01-01

Neural induction is largely considered a default process, whereas little is known about intrinsic factors that drive neural differentiation. Kamiya and colleagues now demonstrate that a transcription factor, Zfp521, is capable of directing embryonic stem (ES) cells into neural progenitors. They discovered that Zfp521 transcripts were enriched in early neural lineage of ES cell differentiation. Forced expression of Zfp521 turned ES cells into neural progenitors in culture conditions that would normally inhibit neural differentiation. Zfp521 was expressed in mouse embryos during gastrulation. The protein was shown to associate with a co-activator p300 and directly induce expression of early neural genes. Knockdown of the Zfp521 by shRNA halted cells at the epiblast stage and suppressed neural differentiation. Zfp521 is a nuclear protein with 30 Krüppel-like zinc fingers mediating multiple protein-protein interactions, and regulates transcription in diverse tissues and organs. The protein promotes proliferation, delays differentiation and reduces apoptosis. The findings by Kamiya and colleagues that Zfp521 directs and sustains early neural differentiation now opens up a series of studies to investigate roles of Zfp521 in stem cells and brain development of mice and men. PMID:21539723

Oral Language: Expression of Thought.

ERIC Educational Resources Information Center

Anastasiow, Nicholas

A child's language reflects his thought processes and his level of development. Motor, emotional, and language development all have a direct relationship to the child's cognitive functioning--each follows the pattern of moving from gross and loosely differentiated states to refined and differentiated systems. Research in early childhood education…

Selection and dynamics of embryonic stem cell integration into early mouse embryos

PubMed Central

Alexandrova, Stoyana; Kalkan, Tuzer; Humphreys, Peter; Riddell, Andrew; Scognamiglio, Roberta; Trumpp, Andreas; Nichols, Jennifer

2016-01-01

The process by which pluripotent cells incorporate into host embryos is of interest to investigate cell potency and cell fate decisions. Previous studies suggest that only a minority of the embryonic stem cell (ESC) inoculum contributes to the adult chimaera. How incoming cells are chosen for integration or elimination remains unclear. By comparing a heterogeneous mix of undifferentiated and differentiating ESCs (serum/LIF) with more homogeneous undifferentiated culture (2i/LIF), we examine the role of cellular heterogeneity in this process. Time-lapse ex vivo imaging revealed a drastic elimination of serum/LIF ESCs during early development in comparison with 2i/LIF ESCs. Using a fluorescent reporter for naive pluripotency (Rex1-GFP), we established that the acutely eliminated serum/LIF ESCs had started to differentiate. The rejected cells were apparently killed by apoptosis. We conclude that a selection process exists by which unwanted differentiating cells are eliminated from the embryo. However, occasional Rex1− cells were able to integrate. Upregulation of Rex1 occurred in a proportion of these cells, reflecting the potential of the embryonic environment to expedite diversion from differentiation priming to enhance the developing embryonic epiblast. PMID:26586221

Siderophile Element Depletion in the Angrite Parent Body (APB) Mantle: Due to Core Formation?

NASA Technical Reports Server (NTRS)

Righter, K.

2008-01-01

The origin of angrites has evaded scientists due in part to unusual mineralogy, oxidized character, and small numbers of samples. Increased interest in the origin of angrites has stemmed from the recovery of approximately 10 new angrites in the past decade. These new samples have allowed meteoriticists to recognize that angrites are compositionally diverse, old, and record very early differentiation. Also, a magma ocean has been proposed to have been involved in APB early differentiation, but this remains untested for siderophile elements which are commonly cited as one of the main lines of evidence for magma oceans on the early Earth, Moon, Mars and eucrite parent body (e.g., [6]). And recent suggestions that angrites may or may not be from Mercury have also peaked interest in these achondrites. Given all of this background, a detailed understanding of the early differentiation process is desired. Previous efforts at examining siderophile element (SE) concentrations with respect to core formation processes in the APB have not resulted in any definite conclusions regarding segregation of a metallic core. The goal of this study is to summarize what is known about SE concentrations in the suite, estimate depletions of SE compared to chondrites, and apply metal/silicate experimental partition coefficients to assess whether the APB had a core.

Protein Synthesis in Relation to Ripening of Pome Fruits 1

PubMed Central

Frenkel, Chaim; Klein, Isaac; Dilley, D. R.

1968-01-01

Protein synthesis by intact Bartlett pear fruits was studied with ripening as measured by flesh softening, chlorophyll degradation, respiration, ethylene synthesis, and malic enzyme activity. Protein synthesis is required for normal ripening, and the proteins synthesized early in the ripening process are, in fact, enzymes required for ripening. 14C-Phenylalanine is differentially incorporated into fruit proteins separated by acrylamide gel electrophoresis of pome fruits taken at successive ripening stages. Capacity for malic enzyme synthesis increases during the early stage of ripening. Fruit ripening and ethylene synthesis are inhibited when protein synthesis is blocked by treatment with cycloheximide at the early-climacteric stage. Cycloheximide became less effective as the climacteric developed. Ethylene did not overcome inhibition of ripening by cycloheximide. The respiratory climacteric is not inhibited by cycloheximide. It is concluded that normal ripening of pome fruits is a highly coordinated process of biochemical differentiation involving directed protein synthesis. PMID:16656897

[Effects of sowing times on the spike differentiation of different wheat varieties under the climate of warm winter].

PubMed

Gao, Qinglu; Xue, Xiang; Wu, Yu; Ru, Zhengang

2003-10-01

Spike differentiation processes and freezing damage of three wheat varieties were studied by sowing in different stages. The results showed that under the condition of weather changing warm, the time of entering each stage of spike differentiation of wheat of strong spring variety was earlier than that of wheat of spring variety and semi-winter variety. Sowing times had more effects on durative time of the elongation stage, single-prism stage and two-prism stage of the spike differentiation. Under sowing early, the stronger the springness of wheat was, the quicker it developed, the higher spike differentiation phases it reached before winter, and the more serious freezing damage it suffered in wintering. According to this, the semi-winter varieties of wheat should be adopted first and arranged in pairs with spring varieties in wheat production, and the sowing times should not be too early as the weather becoming warm.

Lasting effects of early exposure to temperature on the gonadal transcriptome at the time of sex differentiation in the European sea bass, a fish with mixed genetic and environmental sex determination.

PubMed

Díaz, Noelia; Piferrer, Francesc

2015-09-04

Sex in fish is plastic and in several species can be influenced by environmental factors. In sensitive species, elevated temperatures have a masculinizing effect. Previous studies on the effects of temperature on gene expression have been restricted to a few cognate genes, mostly related to testis or ovarian development, and analyzed in gonads once they had completed the process of sex differentiation. However, studies on the effect of temperature at the whole gonadal transcriptomic level are scarce in fish and, in addition, temperature effects at the time of sex differentiation at the transcriptomic level are also unknown. Here, we used the European sea bass, a gonochoristic teleost with a polygenic sex determination system influenced by temperature, and exposed larvae to elevated temperature during the period of early gonad formation. Transcriptomic analysis of the gonads was carried out about three months after the end of temperature exposure, shortly after the beginning of the process of sex differentiation. Elevated temperature doubled the number of males with respect to untreated controls. Transcriptomic analysis of early differentiating female gonads showed how heat caused: 1) an up-regulation of genes related to cholesterol transport (star), the stress response (nr3c1) and testis differentiation (amh, dmrt, etc.), 2) a decrease in the expression of genes related to ovarian differentiation such as cyp19a1a, and 3) an increase in the expression of several genes related to epigenetic regulatory mechanisms (hdac11, dicer1, ehmt2, jarid2a, pcgf2, suz12, mettl22). Taken together, the results of this study contribute to the understanding of how the early environment sets permanent changes that result in long-lasting consequences, in this case in the sexual phenotype. Results also show the usefulness of comparing the effects of heat on the behavior of cognate genes related to sex differentiation as well as that of genes involved in establishing and maintaining cell identity through epigenetic mechanisms.

Differential tissue growth and cell adhesion alone drive early tooth morphogenesis: An ex vivo and in silico study

PubMed Central

Savriama, Yoland; Jernvall, Jukka

2018-01-01

From gastrulation to late organogenesis animal development involves many genetic and bio-mechanical interactions between epithelial and mesenchymal tissues. Ectodermal organs, such as hairs, feathers and teeth are well studied examples of organs whose development is based on epithelial-mesenchymal interactions. These develop from a similar primordium through an epithelial folding and its interaction with the mesenchyme. Despite extensive knowledge on the molecular pathways involved, little is known about the role of bio-mechanical processes in the morphogenesis of these organs. We propose a simple computational model for the biomechanics of one such organ, the tooth, and contrast its predictions against cell-tracking experiments, mechanical relaxation experiments and the observed tooth shape changes over developmental time. We found that two biomechanical processes, differential tissue growth and differential cell adhesion, were enough, in the model, for the development of the 3D morphology of the early tooth germ. This was largely determined by the length and direction of growth of the cervical loops, lateral folds of the enamel epithelium. The formation of these cervical loops was found to require accelerated epithelial growth relative to other tissues and their direction of growth depended on specific differential adhesion between the three tooth tissues. These two processes and geometrical constraints in early tooth bud also explained the shape asymmetry between the lateral cervical loops and those forming in the anterior and posterior of the tooth. By performing mechanical perturbations ex vivo and in silico we inferred the distribution and direction of tensile stresses in the mesenchyme that restricted cervical loop lateral growth and forced them to grow downwards. Overall our study suggests detailed quantitative explanations for how bio-mechanical processes lead to specific morphological 3D changes over developmental time. PMID:29481561

Coordination of cellular differentiation, polarity, mitosis and meiosis - New findings from early vertebrate oogenesis.

PubMed

Elkouby, Yaniv M; Mullins, Mary C

2017-10-15

A mechanistic dissection of early oocyte differentiation in vertebrates is key to advancing our knowledge of germline development, reproductive biology, the regulation of meiosis, and all of their associated disorders. Recent advances in the field include breakthroughs in the identification of germline stem cells in Medaka, in the cellular architecture of the germline cyst in mice, in a mechanistic dissection of chromosomal pairing and bouquet formation in meiosis in mice, in tracing oocyte symmetry breaking to the chromosomal bouquet of meiosis in zebrafish, and in the biology of the Balbiani body, a universal oocyte granule. Many of the major events in early oogenesis are universally conserved, and some are co-opted for species-specific needs. The chromosomal events of meiosis are of tremendous consequence to gamete formation and have been extensively studied. New light is now being shed on other aspects of early oocyte differentiation, which were traditionally considered outside the scope of meiosis, and their coordination with meiotic events. The emerging theme is of meiosis as a common groundwork for coordinating multifaceted processes of oocyte differentiation. In an accompanying manuscript we describe methods that allowed for investigations in the zebrafish ovary to contribute to these breakthroughs. Here, we review these advances mostly from the zebrafish and mouse. We discuss oogenesis concepts across established model organisms, and construct an inclusive paradigm for early oocyte differentiation in vertebrates. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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

2017-07-01

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

Neural Correlates of Attentional Processing of Threat in Youth with and without Anxiety Disorders.

PubMed

Bechor, Michele; Ramos, Michelle L; Crowley, Michael J; Silverman, Wendy K; Pettit, Jeremy W; Reeb-Sutherland, Bethany C

2018-04-02

Late-stage attentional processing of threatening stimuli, quantified through event-related potentials (ERPs), differentiates youth with and without anxiety disorders. It is unknown whether early-stage attentional processing of threatening stimuli differentiates these groups. Examining both early and late stage attentional processes in youth may advance knowledge and enhance efforts to identify biomarkers for translational prevention and treatment research. Twenty-one youth with primary DSM-IV-TR anxiety disorders (10 males, ages 8-15 years) and 21 typically developing Controls (15 males, ages 8-16 years) completed a dot probe task while electroencephalography (EEG) was recorded, and ERPs were examined. Youth with anxiety disorders showed significantly larger (more positive) P1 amplitudes for threatening stimuli than for neutral stimuli, and Controls showed the opposite pattern. Youth with anxiety showed larger (more negative) N170 amplitudes compared with Controls. Controls showed significantly larger (more positive) P2 and P3 amplitudes, regardless of stimuli valence, compared with youth with anxiety disorders. ERPs observed during the dot probe task indicate youth with anxiety disorders display distinct neural processing during early stage attentional orienting and processing of faces; this was not the case for Controls. Such results suggest these ERP components may have potential as biomarkers of anxiety disorders in youth.

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

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

PubMed Central

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

2015-01-01

Background and Aims 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. Methods 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. Key Results 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. Conclusions 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. PMID:26002256

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.

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.

Magma oceanography. I - Thermal evolution. [of lunar surface

NASA Technical Reports Server (NTRS)

Solomon, S. C.; Longhi, J.

1977-01-01

Fractional crystallization and flotation of cumulate plagioclase in a cooling 'magma ocean' provides the simplest explanation for early emplacement of a thick feldspar-rich lunar crust. The complementary mafic cumulates resulting from the differentiation of such a magma ocean have been identified as the ultimate source of mare basalt liquids on the basis or rare-earth abundance patterns and experimental petrology studies. A study is conducted concerning the thermal evolution of the early differentiation processes. A range of models of increasing sophistication are considered. The models developed contain the essence of the energetics and the time scale for magma ocean differentiation. Attention is given to constraints on a magma ocean, modeling procedures, single-component magma oceans, fractionating magma oceans, and evolving magma oceans.

Analysis of global gene expression profiles to identify differentially expressed genes critical for embryo development in Brassica rapa.

PubMed

Zhang, Yu; Peng, Lifang; Wu, Ya; Shen, Yanyue; Wu, Xiaoming; Wang, Jianbo

2014-11-01

Embryo development represents a crucial developmental period in the life cycle of flowering plants. To gain insights into the genetic programs that control embryo development in Brassica rapa L., RNA sequencing technology was used to perform transcriptome profiling analysis of B. rapa developing embryos. The results generated 42,906,229 sequence reads aligned with 32,941 genes. In total, 27,760, 28,871, 28,384, and 25,653 genes were identified from embryos at globular, heart, early cotyledon, and mature developmental stages, respectively, and analysis between stages revealed a subset of stage-specific genes. We next investigated 9,884 differentially expressed genes with more than fivefold changes in expression and false discovery rate ≤ 0.001 from three adjacent-stage comparisons; 1,514, 3,831, and 6,633 genes were detected between globular and heart stage embryo libraries, heart stage and early cotyledon stage, and early cotyledon and mature stage, respectively. Large numbers of genes related to cellular process, metabolism process, response to stimulus, and biological process were expressed during the early and middle stages of embryo development. Fatty acid biosynthesis, biosynthesis of secondary metabolites, and photosynthesis-related genes were expressed predominantly in embryos at the middle stage. Genes for lipid metabolism and storage proteins were highly expressed in the middle and late stages of embryo development. We also identified 911 transcription factor genes that show differential expression across embryo developmental stages. These results increase our understanding of the complex molecular and cellular events during embryo development in B. rapa and provide a foundation for future studies on other oilseed crops.

Ubiquitination dynamics in the early-branching eukaryote Giardia intestinalis

PubMed Central

Niño, Carlos A; Chaparro, Jenny; Soffientini, Paolo; Polo, Simona; Wasserman, Moises

2013-01-01

Ubiquitination is a highly dynamic and versatile posttranslational modification that regulates protein function, stability, and interactions. To investigate the roles of ubiquitination in a primitive eukaryotic lineage, we utilized the early-branching eukaryote Giardia intestinalis. Using a combination of biochemical, immunofluorescence-based, and proteomics approaches, we assessed the ubiquitination status during the process of differentiation in Giardia. We observed that different types of ubiquitin modifications present specific cellular and temporal distribution throughout the Giardia life cycle from trophozoites to cyst maturation. Ubiquitin signal was detected in the wall of mature cysts, and enzymes implicated in cyst wall biogenesis were identified as substrates for ubiquitination. Interestingly, inhibition of proteasome activity did not affect trophozoite replication and differentiation, while it caused a decrease in cyst viability, arguing for proteasome involvement in cyst wall maturation. Using a proteomics approach, we identified around 200 high-confidence ubiquitinated candidates that vary their ubiquitination status during differentiation. Our results indicate that ubiquitination is critical for several cellular processes in this primitive eukaryote. PMID:23613346

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.

Developmental Progression in the Coral Acropora digitifera Is Controlled by Differential Expression of Distinct Regulatory Gene Networks

PubMed Central

Reyes-Bermudez, Alejandro; Villar-Briones, Alejandro; Ramirez-Portilla, Catalina; Hidaka, Michio; Mikheyev, Alexander S.

2016-01-01

Corals belong to the most basal class of the Phylum Cnidaria, which is considered the sister group of bilaterian animals, and thus have become an emerging model to study the evolution of developmental mechanisms. Although cell renewal, differentiation, and maintenance of pluripotency are cellular events shared by multicellular animals, the cellular basis of these fundamental biological processes are still poorly understood. To understand how changes in gene expression regulate morphogenetic transitions at the base of the eumetazoa, we performed quantitative RNA-seq analysis during Acropora digitifera’s development. We collected embryonic, larval, and adult samples to characterize stage-specific transcription profiles, as well as broad expression patterns. Transcription profiles reconstructed development revealing two main expression clusters. The first cluster grouped blastula and gastrula and the second grouped subsequent developmental time points. Consistently, we observed clear differences in gene expression between early and late developmental transitions, with higher numbers of differentially expressed genes and fold changes around gastrulation. Furthermore, we identified three coexpression clusters that represented discrete gene expression patterns. During early transitions, transcriptional networks seemed to regulate cellular fate and morphogenesis of the larval body. In late transitions, these networks seemed to play important roles preparing planulae for switch in lifestyle and regulation of adult processes. Although developmental progression in A. digitifera is regulated to some extent by differential coexpression of well-defined gene networks, stage-specific transcription profiles appear to be independent entities. While negative regulation of transcription is predominant in early development, cell differentiation was upregulated in larval and adult stages. PMID:26941230

Early-stage detection of VE-cadherin during endothelial differentiation of human mesenchymal stem cells using SPR biosensor.

PubMed

Fathi, Farzaneh; Rezabakhsh, Aysa; Rahbarghazi, Reza; Rashidi, Mohammad-Reza

2017-10-15

Surface plasmon resonance (SPR) biosensors are most commonly applied for real-time dynamic analysis and measurement of interactions in bio-molecular studies and cell-surface analysis without the need for labeling processes. Up to present, SPR application in stem cell biology and biomedical sciences was underused. Herein, a very simple and sensitive method was developed to evaluate human mesenchymal stem cells trans-differentiation to endothelial lineage of over a period of 14 days based on VE-cadherin biomarker. The SPR signals increased with the increase of the amount of VE-cadherin expression on the cell surface during cell differentiation process. The method was able to detect ≈27 cells permm 2 . No significant effect was observed on the cell viability during the cell attachment to the surface of immune-reactive biochips and during the SPR analysis. Using this highly sensitive SPR method, it was possible to sense the early stage of endothelial differentiation on day 3 in label-free form, whereas flow cytometry and fluorescent microscopy methods were found unable to detect the cell differentiation at the same time. Therefore, the proposed method can rapidly and accurately detect cell differentiation in live cells and label-free manner without any need of cell breakage and has great potential for both diagnostic and experimental approaches. Copyright © 2017. Published by Elsevier B.V.

Differentiating Processes of Control and Understanding in the Early Development of Emotion and Cognition

ERIC Educational Resources Information Center

Blankson, A. Nayena; O'Brien, Marion; Leerkes, Esther M.; Marcovitch, Stuart; Calkins, Susan D.

2012-01-01

In this study, we examined the hypothesis that preschoolers' performance on emotion and cognitive tasks is organized into discrete processes of control and understanding within the domains of emotion and cognition. Additionally, we examined the relations among component processes using mother report, behavioral observation, and physiological…

Electrophysiological evidence of altered visual processing in adults who experienced visual deprivation during infancy.

PubMed

Segalowitz, Sidney J; Sternin, Avital; Lewis, Terri L; Dywan, Jane; Maurer, Daphne

2017-04-01

We examined the role of early visual input in visual system development by testing adults who had been born with dense bilateral cataracts that blocked all patterned visual input during infancy until the cataractous lenses were removed surgically and the eyes fitted with compensatory contact lenses. Patients viewed checkerboards and textures to explore early processing regions (V1, V2), Glass patterns to examine global form processing (V4), and moving stimuli to explore global motion processing (V5). Patients' ERPs differed from those of controls in that (1) the V1 component was much smaller for all but the simplest stimuli and (2) extrastriate components did not differentiate amongst texture stimuli, Glass patterns, or motion stimuli. The results indicate that early visual deprivation contributes to permanent abnormalities at early and mid levels of visual processing, consistent with enduring behavioral deficits in the ability to process complex textures, global form, and global motion. © 2017 Wiley Periodicals, Inc.

Early differential sensitivity of evoked-potentials to local and global shape during the perception of three-dimensional objects.

PubMed

Leek, E Charles; Roberts, Mark; Oliver, Zoe J; Cristino, Filipe; Pegna, Alan J

2016-08-01

Here we investigated the time course underlying differential processing of local and global shape information during the perception of complex three-dimensional (3D) objects. Observers made shape matching judgments about pairs of sequentially presented multi-part novel objects. Event-related potentials (ERPs) were used to measure perceptual sensitivity to 3D shape differences in terms of local part structure and global shape configuration - based on predictions derived from hierarchical structural description models of object recognition. There were three types of different object trials in which stimulus pairs (1) shared local parts but differed in global shape configuration; (2) contained different local parts but shared global configuration or (3) shared neither local parts nor global configuration. Analyses of the ERP data showed differential amplitude modulation as a function of shape similarity as early as the N1 component between 146-215ms post-stimulus onset. These negative amplitude deflections were more similar between objects sharing global shape configuration than local part structure. Differentiation among all stimulus types was reflected in N2 amplitude modulations between 276-330ms. sLORETA inverse solutions showed stronger involvement of left occipitotemporal areas during the N1 for object discrimination weighted towards local part structure. The results suggest that the perception of 3D object shape involves parallel processing of information at local and global scales. This processing is characterised by relatively slow derivation of 'fine-grained' local shape structure, and fast derivation of 'coarse-grained' global shape configuration. We propose that the rapid early derivation of global shape attributes underlies the observed patterns of N1 amplitude modulations. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Early transcriptional and epigenetic regulation of CD8+ T cell differentiation revealed by single-cell RNA-seq

PubMed Central

Kakaradov, Boyko; Arsenio, Janilyn; Widjaja, Christella E.; He, Zhaoren; Aigner, Stefan; Metz, Patrick J.; Yu, Bingfei; Wehrens, Ellen J.; Lopez, Justine; Kim, Stephanie H.; Zuniga, Elina I.; Goldrath, Ananda W.; Chang, John T.; Yeo, Gene W.

2017-01-01

SUMMARY During microbial infection, responding CD8+ T lymphocytes differentiate into heterogeneous subsets that together provide immediate and durable protection. To elucidate the dynamic transcriptional changes that underlie this process, we applied a single-cell RNA sequencing approach and analyzed individual CD8+ T lymphocytes sequentially throughout the course of a viral infection in vivo. Our analyses revealed a striking transcriptional divergence among cells that had undergone their first division and identified previously unknown molecular determinants controlling CD8+ T lymphocyte fate specification. These findings suggest a model of terminal effector cell differentiation initiated by an early burst of transcriptional activity and subsequently refined by epigenetic silencing of transcripts associated with memory lymphocytes, highlighting the power and necessity of single-cell approaches. PMID:28218746

Pipette-based Method to Study Embryoid Body Formation Derived from Mouse and Human Pluripotent Stem Cells Partially Recapitulating Early Embryonic Development Under Simulated Microgravity Conditions

NASA Astrophysics Data System (ADS)

Shinde, Vaibhav; Brungs, Sonja; Hescheler, Jürgen; Hemmersbach, Ruth; Sachinidis, Agapios

2016-06-01

The in vitro differentiation of pluripotent stem cells partially recapitulates early in vivo embryonic development. More recently, embryonic development under the influence of microgravity has become a primary focus of space life sciences. In order to integrate the technique of pluripotent stem cell differentiation with simulated microgravity approaches, the 2-D clinostat compatible pipette-based method was experimentally investigated and adapted for investigating stem cell differentiation processes under simulated microgravity conditions. In order to keep residual accelerations as low as possible during clinorotation, while also guaranteeing enough material for further analysis, stem cells were exposed in 1-mL pipettes with a diameter of 3.5 mm. The differentiation of mouse and human pluripotent stem cells inside the pipettes resulted in the formation of embryoid bodies at normal gravity (1 g) after 24 h and 3 days. Differentiation of the mouse pluripotent stem cells on a 2-D pipette-clinostat for 3 days also resulted in the formation of embryoid bodies. Interestingly, the expression of myosin heavy chain was downregulated when cultivation was continued for an additional 7 days at normal gravity. This paper describes the techniques for culturing and differentiation of pluripotent stem cells and exposure to simulated microgravity during culturing or differentiation on a 2-D pipette clinostat. The implementation of these methodologies along with -omics technologies will contribute to understand the mechanisms regulating how microgravity influences early embryonic development.

Understanding the Process Model of Leadership: Follower Attribute Design and Assessment

ERIC Educational Resources Information Center

Antelo, Absael; Henderson, Richard L.; St. Clair, Norman

2010-01-01

Early leadership studies produced significant research findings that have helped differentiate between leader and follower personal attributes and their consequent behaviors (SEDL, 1992), but little attention was given to the follower's contribution to the leadership process. This study represents a continuation of research by Henderson, Antelo, &…

Aym1, a mouse meiotic gene identified by virtue of its ability to activate early meiotic genes in the yeast Saccharomyces cerevisiae.

PubMed

Malcov, Mira; Cesarkas, Karen; Stelzer, Gil; Shalom, Sarah; Dicken, Yosef; Naor, Yaniv; Goldstein, Ronald S; Sagee, Shira; Kassir, Yona; Don, Jeremy

2004-12-01

Our understanding of the molecular mechanisms that operate during differentiation of mitotically dividing spermatogonia cells into spermatocytes lags way behind what is known about other differentiating systems. Given the evolutionary conservation of the meiotic process, we screened for mouse proteins that could specifically activate early meiotic promoters in Saccharomyces cerevisiae yeast cells, when fused to the Gal4 activation domain (Gal4AD). Our screen yielded the Aym1 gene that encodes a short peptide of 45 amino acids. We show that a Gal4AD-AYM1 fusion protein activates expression of reporter genes through the promoters of the early meiosis-specific genes IME2 and HOP1, and that this activation is dependent on the DNA-binding protein Ume6. Aym1 is transcribed predominantly in mouse primary spermatocytes and in gonads of female embryos undergoing the corresponding meiotic divisions. Aym1 immunolocalized to nuclei of primary spermatocytes and oocytes and to specific type A spermatogonia cells, suggesting it might play a role in the processes leading to meiotic competence. The potential functional relationship between AYM1 and yeast proteins that regulate expression of early meiotic genes is discussed.

Differential Phonological and Semantic Modulation of Neurophysiological Responses to Visual Word Recognition.

PubMed

Drakesmith, Mark; El-Deredy, Wael; Welbourne, Stephen

2015-01-01

Reading words for meaning relies on orthographic, phonological and semantic processing. The triangle model implicates a direct orthography-to-semantics pathway and a phonologically mediated orthography-to-semantics pathway, which interact with each other. The temporal evolution of processing in these routes is not well understood, although theoretical evidence predicts early phonological processing followed by interactive phonological and semantic processing. This study used electroencephalography-event-related potential (ERP) analysis and magnetoencephalography (MEG) source localisation to identify temporal markers and the corresponding neural generators of these processes in early (∼200 ms) and late (∼400 ms) neurophysiological responses to visual words, pseudowords and consonant strings. ERP showed an effect of phonology but not semantics in both time windows, although at ∼400 ms there was an effect of stimulus familiarity. Phonological processing at ~200 ms was localised to the left occipitotemporal cortex and the inferior frontal gyrus. At 400 ms, there was continued phonological processing in the inferior frontal gyrus and additional semantic processing in the anterior temporal cortex. There was also an area in the left temporoparietal junction which was implicated in both phonological and semantic processing. In ERP, the semantic response at ∼400 ms appeared to be masked by concurrent processes relating to familiarity, while MEG successfully differentiated these processes. The results support the prediction of early phonological processing followed by an interaction of phonological and semantic processing during word recognition. Neuroanatomical loci of these processes are consistent with previous neuropsychological and functional magnetic resonance imaging studies. The results also have implications for the classical interpretation of N400-like responses as markers for semantic processing.

Live Cell Imaging of the Nascent Inactive X Chromosome during the Early Differentiation Process of Naive ES Cells towards Epiblast Stem Cells

PubMed Central

Guyochin, Aurélia; Maenner, Sylvain; Chu, Erin Tsi-Jia; Hentati, Asma; Attia, Mikael; Avner, Philip; Clerc, Philippe

2014-01-01

Random X-chromosome inactivation ensures dosage compensation in mammals through the transcriptional silencing of one of the two X chromosomes present in each female cell. Silencing is initiated in the differentiating epiblast of the mouse female embryos through coating of the nascent inactive X chromosome by the non-coding RNA Xist, which subsequently recruits the Polycomb Complex PRC2 leading to histone H3-K27 methylation. Here we examined in mouse ES cells the early steps of the transition from naive ES cells towards epiblast stem cells as a model for inducing X chromosome inactivation in vitro. We show that these conditions efficiently induce random XCI. Importantly, in a transient phase of this differentiation pathway, both X chromosomes are coated with Xist RNA in up to 15% of the XX cells. In an attempt to determine the dynamics of this process, we designed a strategy aimed at visualizing the nascent inactive X-chromosome in live cells. We generated transgenic female XX ES cells expressing the PRC2 component Ezh2 fused to the fluorescent protein Venus. The fluorescent fusion protein was expressed at sub-physiological levels and located in nuclei of ES cells. Upon differentiation of ES cell towards epiblast stem cell fate, Venus-fluorescent territories appearing in interphase nuclei were identified as nascent inactive X chromosomes by their association with Xist RNA. Imaging of Ezh2-Venus for up to 24 hours during the differentiation process showed survival of some cells with two fluorescent domains and a surprising dynamics of the fluorescent territories across cell division and in the course of the differentiation process. Our data reveal a strategy for visualizing the nascent inactive X chromosome and suggests the possibility for a large plasticity of the nascent inactive X chromosome. PMID:25546018

A role for autophagic protein beclin 1 early in lymphocyte development.

PubMed

Arsov, Ivica; Adebayo, Adeola; Kucerova-Levisohn, Martina; Haye, Joanna; MacNeil, Margaret; Papavasiliou, F Nina; Yue, Zhenyu; Ortiz, Benjamin D

2011-02-15

Autophagy is a highly regulated and evolutionarily conserved process of cellular self-digestion. Recent evidence suggests that this process plays an important role in regulating T cell homeostasis. In this study, we used Rag1(-/-) (recombination activating gene 1(-/-)) blastocyst complementation and in vitro embryonic stem cell differentiation to address the role of Beclin 1, one of the key autophagic proteins, in lymphocyte development. Beclin 1-deficient Rag1(-/-) chimeras displayed a dramatic reduction in thymic cellularity compared with control mice. Using embryonic stem cell differentiation in vitro, we found that the inability to maintain normal thymic cellularity is likely caused by impaired maintenance of thymocyte progenitors. Interestingly, despite drastically reduced thymocyte numbers, the peripheral T cell compartment of Beclin 1-deficient Rag1(-/-) chimeras is largely normal. Peripheral T cells displayed normal in vitro proliferation despite significantly reduced numbers of autophagosomes. In addition, these chimeras had greatly reduced numbers of early B cells in the bone marrow compared with controls. However, the peripheral B cell compartment was not dramatically impacted by Beclin 1 deficiency. Collectively, our results suggest that Beclin 1 is required for maintenance of undifferentiated/early lymphocyte progenitor populations. In contrast, Beclin 1 is largely dispensable for the initial generation and function of the peripheral T and B cell compartments. This indicates that normal lymphocyte development involves Beclin 1-dependent, early-stage and distinct, Beclin 1-independent, late-stage processes.

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

New insights in osteogenic differentiation revealed by mass spectrometric assessment of phosphorylated substrates in murine skin mesenchymal cells

PubMed Central

2013-01-01

Background Bone fractures and loss represent significant costs for the public health system and often affect the patients quality of life, therefore, understanding the molecular basis for bone regeneration is essential. Cytokines, such as IL-6, IL-10 and TNFα, secreted by inflammatory cells at the lesion site, at the very beginning of the repair process, act as chemotactic factors for mesenchymal stem cells, which proliferate and differentiate into osteoblasts through the autocrine and paracrine action of bone morphogenetic proteins (BMPs), mainly BMP-2. Although it is known that BMP-2 binds to ActRI/BMPR and activates the SMAD 1/5/8 downstream effectors, little is known about the intracellular mechanisms participating in osteoblastic differentiation. We assessed differences in the phosphorylation status of different cellular proteins upon BMP-2 osteogenic induction of isolated murine skin mesenchymal stem cells using Triplex Stable Isotope Dimethyl Labeling coupled with LC/MS. Results From 150 μg of starting material, 2,264 proteins were identified and quantified at five different time points, 235 of which are differentially phosphorylated. Kinase motif analysis showed that several substrates display phosphorylation sites for Casein Kinase, p38, CDK and JNK. Gene ontology analysis showed an increase in biological processes related with signaling and differentiation at early time points after BMP2 induction. Moreover, proteins involved in cytoskeleton rearrangement, Wnt and Ras pathways were found to be differentially phosphorylated during all timepoints studied. Conclusions Taken together, these data, allow new insights on the intracellular substrates which are phosphorylated early on during differentiation to BMP2-driven osteoblastic differentiation of skin-derived mesenchymal stem cells. PMID:24148232

Biracial and Monoracial Infant Own-Race Face Perception: An Eye Tracking Study

ERIC Educational Resources Information Center

Gaither, Sarah E.; Pauker, Kristin; Johnson, Scott P.

2012-01-01

We know that early experience plays a crucial role in the development of face processing, but we know little about how infants learn to distinguish faces from different races, especially for non-Caucasian populations. Moreover, it is unknown whether differential processing of different race faces observed in typically studied monoracial infants…

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

PubMed

Schulz, Edda G

2017-11-05

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

Wnt/beta-catenin pathway activation and myogenic differentiation are induced by cholesterol depletion.

PubMed

Mermelstein, Cláudia S; Portilho, Débora M; Mendes, Fábio A; Costa, Manoel L; Abreu, José Garcia

2007-03-01

Myogenic differentiation is a multistep process that begins with the commitment of mononucleated precursors that withdraw from cell cycle. These myoblasts elongate while aligning to each other, guided by the recognition between their membranes. This step is followed by cell fusion and the formation of long and striated multinucleated myotubes. We have recently shown that cholesterol depletion by methyl-beta-cyclodextrin (MbetaCD) induces myogenic differentiation by enhancing myoblast recognition and fusion. Here, we further studied the signaling pathways responsible for early steps of myogenesis. As it is known that Wnt plays a role in muscle differentiation, we used the chemical MbetaCD to deplete membrane cholesterol and investigate the involvement of the Wnt/beta-catenin pathway during myogenesis. We show that cholesterol depletion promoted a significant increase in expression of beta-catenin, its nuclear translocation and activation of the Wnt pathway. Moreover, we show that the activation of the Wnt pathway after cholesterol depletion can be inhibited by the soluble protein Frzb-1. Our data suggest that membrane cholesterol is involved in Wnt/beta-catenin signaling in the early steps of myogenic differentiation.

Expression of voltage-activated calcium channels in the early zebrafish embryo.

PubMed

Sanhueza, Dayán; Montoya, Andro; Sierralta, Jimena; Kukuljan, Manuel

2009-05-01

Increases in cytosolic calcium concentrations regulate many cellular processes, including aspects of early development. Calcium release from intracellular stores and calcium entry through non-voltage-gated channels account for signalling in non-excitable cells, whereas voltage-gated calcium channels (CaV) are important in excitable cells. We report the expression of multiple transcripts of CaV, identified by its homology to other species, in the early embryo of the zebrafish, Danio rerio, at stages prior to the differentiation of excitable cells. CaV mRNAs and proteins were detected as early as the 2-cell stages, which indicate that they arise from both maternal and zygotic transcription. Exposure of embryos to pharmacological blockers of CaV does not perturb early development significantly, although late effects are appreciable. These results suggest that CaV may have a role in calcium homeostasis and control of cellular process during early embryonic development.

Morphological and proteomic analysis of early stage of osteoblast differentiation in osteoblastic progenitor cells

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

Hong, Dun; Orthopedic Department, Taizhou Hospital, Wenzhou Medical College, Linhai, Zhejiang 317000; Chen, Hai-Xiao, E-mail: Hxchen-1@163.net

Bone remodeling relies on a dynamic balance between bone formation and resorption, mediated by osteoblasts and osteoclasts, respectively. Under certain stimuli, osteoprogenitor cells may differentiate into premature osteoblasts and further into mature osteoblasts. This process is marked by increased alkaline phosphatase (ALP) activity and mineralized nodule formation. In this study, we induced osteoblast differentiation in mouse osteoprogenitor MC3T3-E1 cells and divided the process into three stages. In the first stage (day 3), the MC3T3-E1 cell under osteoblast differentiation did not express ALP or deposit a mineralized nodule. In the second stage, the MC3T3-E1 cell expressed ALP but did not formmore » a mineralized nodule. In the third stage, the MC3T3-E1 cell had ALP activity and formed mineralized nodules. In the present study, we focused on morphological and proteomic changes of MC3T3-E1 cells in the early stage of osteoblast differentiation - a period when premature osteoblasts transform into mature osteoblasts. We found that mean cell area and mean stress fiber density were increased in this stage due to enhanced cell spreading and decreased cell proliferation. We further analyzed the proteins in the signaling pathway of regulation of the cytoskeleton using a proteomic approach and found upregulation of IQGAP1, gelsolin, moesin, radixin, and Cfl1. After analyzing the focal adhesion signaling pathway, we found the upregulation of FLNA, LAMA1, LAMA5, COL1A1, COL3A1, COL4A6, and COL5A2 as well as the downregulation of COL4A1, COL4A2, and COL4A4. In conclusion, the signaling pathway of regulation of the cytoskeleton and focal adhesion play critical roles in regulating cell spreading and actin skeleton formation in the early stage of osteoblast differentiation.« less

Pristine Igneous Rocks and the Early Differentiation of Planetary Materials

NASA Technical Reports Server (NTRS)

Warren, Paul H.

2005-01-01

Our studies are highly interdisciplinary, but are focused on the processes and products of early planetary and asteroidal differentiation, especially the genesis of the ancient lunar crust. The compositional diversity that we explore is the residue of process diversity, which has strong relevance for comparative planetology. Most of the accessible lunar crust consists of materials hybridized by impact-mixing. Our lunar research concentrates on the rare pristine (unmixed) samples that reflect the original genetic diversity of the early crust. Among HED basalts (eucrites and clasts in howardites), we distinguish as pristine the small minority that escaped the pervasive thermal metamorphism of the parent asteroid's crust. We have found a correlation between metamorphically pristine HED basalts and the similarly small minority of compositionally evolved "Stannern trend" samples, which are enriched in incompatible elements and titanium compared to main group eucrites, and yet have relatively high mg ratios. Other topics under investigation included: lunar and SNC (martian?) meteorites; igneous meteorites in general; impact breccias, especially metal-rich Apollo samples and polymict eucrites; siderophile compositions of the lunar and martian mantles; and planetary bulk compositions and origins.

Identification of candidate miRNAs and expression profile of yak oocytes before and after in vitro maturation by high-throughput sequencing.

PubMed

Xiong, X R; Lan, D L; Li, J; Zi, X D; Li, M Y

2016-12-01

Small RNA represents several unique non-coding RNA classes that have important function in a wide range of biological processes including development of germ cells and early embryonic, cell differentiation, cell proliferation and apoptosis in diverse organisms. However, little is known about their expression profiles and effects in yak oocytes maturation and early development. To investigate the function of small RNAs in the maturation process of yak oocyte and early development, two small RNA libraries of oocytes were constructed from germinal vesicle stage (GV) and maturation in vitro to metaphase II-arrested stage (M II) and then sequenced using small RNA high-throughput sequencing technology. A total of 9,742,592 and 12,168,523 clean reads were obtained from GV and M II oocytes, respectively. In total, 801 and 1,018 known miRNAs were acquired from GV and M II oocytes, and 75 miRNAs were found to be significantly differentially expressed: 47 miRNAs were upregulated and 28 miRNAs were downregulated in the M II oocytes compared to the GV stage. Among the upregulated miRNAs, miR-342 has the largest fold change (9.25-fold). Six highly expressed miRNAs (let-7i, miR-10b, miR-10c, miR-143, miR-146b and miR-148) were validated by real-time quantitative PCR (RT-qPCR) and consistent with the sequencing results. Furthermore, the expression patterns of two miRNAs and their potential targets were analysed in different developmental stages of oocytes and early embryos. This study provides the first miRNA profile in the mature process of yak oocyte. Seventy-five miRNAs are expressed differentially in GV and M II oocytes as well as among different development stages of early embryos, suggesting miRNAs involved in regulating oocyte maturation and early development of yak. These results showed specific miRNAs in yak oocytes had dynamic changes during meiosis. Further functional and mechanistic studies on the miRNAs during meiosis may beneficial to understanding the role of miRNAs on meiotic division. © 2016 Blackwell Verlag GmbH.

Tuberin and PRAS40 are anti-apoptotic gatekeepers during early human amniotic fluid stem-cell differentiation.

PubMed

Fuchs, Christiane; Rosner, Margit; Dolznig, Helmut; Mikula, Mario; Kramer, Nina; Hengstschläger, Markus

2012-03-01

Embryoid bodies (EBs) are three-dimensional multicellular aggregates allowing the in vitro investigation of stem-cell differentiation processes mimicking early embryogenesis. Human amniotic fluid stem (AFS) cells harbor high proliferation potential, do not raise the ethical issues of embryonic stem cells, have a lower risk for tumor development, do not need exogenic induction of pluripotency and are chromosomal stable. Starting from a single human AFS cell, EBs can be formed accompanied by the differentiation into cells of all three embryonic germ layers. Here, we report that siRNA-mediated knockdown of the endogenous tuberous sclerosis complex-2 (TSC2) gene product tuberin or of proline-rich Akt substrate of 40 kDa (PRAS40), the two major negative regulators of mammalian target of rapamycin (mTOR), leads to massive apoptotic cell death during EB development of human AFS cells without affecting the endodermal, mesodermal and ectodermal cell differentiation spectrum. Co-knockdown of endogenous mTOR demonstrated these effects to be mTOR-dependent. Our findings prove this enzyme cascade to be an essential anti-apoptotic gatekeeper of stem-cell differentiation during EB formation. These data allow new insights into the regulation of early stem-cell maintenance and differentiation and identify a new role of the tumor suppressor tuberin and the oncogenic protein PRAS40 with the relevance for a more detailed understanding of the pathogenesis of diseases associated with altered activities of these gene products.

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.

Effective myotube formation in human adipose tissue-derived stem cells expressing dystrophin and myosin heavy chain by cellular fusion with mouse C2C12 myoblasts

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

Eom, Young Woo; Biomedical Research Institute, Lifeliver Co., Ltd., Suwon; Lee, Jong Eun

2011-04-29

Highlights: {yields} hASCs were differentiated into skeletal muscle cells by treatment with 5-azacytidine, FGF-2, and the supernatant of cultured hASCs. {yields} Dystrophin and MyHC were expressed in late differentiation step by treatment with the supernatant of cultured hASCs. {yields} hASCs expressing dystrophin and MyHC contributed to myotube formation during co-culture with mouse myoblast C2C12 cells. -- Abstract: Stem cell therapy for muscular dystrophies requires stem cells that are able to participate in the formation of new muscle fibers. However, the differentiation steps that are the most critical for this process are not clear. We investigated the myogenic phases of humanmore » adipose tissue-derived stem cells (hASCs) step by step and the capability of myotube formation according to the differentiation phase by cellular fusion with mouse myoblast C2C12 cells. In hASCs treated with 5-azacytidine and fibroblast growth factor-2 (FGF-2) for 1 day, the early differentiation step to express MyoD and myogenin was induced by FGF-2 treatment for 6 days. Dystrophin and myosin heavy chain (MyHC) expression was induced by hASC conditioned medium in the late differentiation step. Myotubes were observed only in hASCs undergoing the late differentiation step by cellular fusion with C2C12 cells. In contrast, hASCs that were normal or in the early stage were not involved in myotube formation. Our results indicate that stem cells expressing dystrophin and MyHC are more suitable for myotube formation by co-culture with myoblasts than normal or early differentiated stem cells expressing MyoD and myogenin.« less

Germ layer differentiation during early hindgut and cloaca formation in rabbit and pig embryos

PubMed Central

Hassoun, Romia; Schwartz, Peter; Rath, Detlef; Viebahn, Christoph; Männer, Jörg

2010-01-01

Relative to recent advances in understanding molecular requirements for endoderm differentiation, the dynamics of germ layer morphology and the topographical distribution of molecular factors involved in endoderm formation at the caudal pole of the embryonic disc are still poorly defined. To discover common principles of mammalian germ layer development, pig and rabbit embryos at late gastrulation and early neurulation stages were analysed as species with a human-like embryonic disc morphology, using correlative light and electron microscopy. Close intercellular contact but no direct structural evidence of endoderm formation such as mesenchymal–epithelial transition between posterior primitive streak mesoderm and the emerging posterior endoderm were found. However, a two-step process closely related to posterior germ layer differentiation emerged for the formation of the cloacal membrane: (i) a continuous mesoderm layer and numerous patches of electron-dense flocculent extracellular matrix mark the prospective region of cloacal membrane formation; and (ii) mesoderm cells and all extracellular matrix including the basement membrane are lost locally and close intercellular contact between the endoderm and ectoderm is established. The latter process involves single cells at first and then gradually spreads to form a longitudinally oriented seam-like cloacal membrane. These gradual changes were found from gastrulation to early somite stages in the pig, whereas they were found from early somite to mid-somite stages in the rabbit; in both species cloacal membrane formation is complete prior to secondary neurulation. The results highlight the structural requirements for endoderm formation during development of the hindgut and suggest new mechanisms for the pathogenesis of common urogenital and anorectal malformations. PMID:20874819

Initiation of follicular atresia: gene networks during early atresia in pig ovaries.

PubMed

Zhang, Jinbi; Liu, Yang; Yao, Wang; Li, Qifa; Liu, Hong-Lin; Pan, Zengxiang

2018-05-09

In mammals, more than 99% of ovarian follicles undergo a degenerative process known as atresia. The molecular events involve in atresia initiation remain incompletely understood. The objective of this study was to analyze differential gene expression profiles of medium antral ovarian follicles during early atresia in pig. The transcriptome evaluation was performed on cDNA microarrays using healthy and early atretic follicle samples and was validated by quantitative PCR. Annotation analysis applying current database (sus scrofa 11.1) revealed 450 significantly differential expressed genes between healthy and early atretic follicles. Among them, 142 were significantly up-regulated in early atretic with respect to healthy group and 308 were down-regulated. Similar expression trends were observed between microarray data and qRT-PCR confirmation, which indicated the reliability of the microarray analysis. Further analysis of the differential expressed genes revealed the most significantly affected biological functions during early atresia including blood vessel development, regulation of DNA-templated transcription in response to stress and negative regulation of cell adhesion. The pathway and interaction analysis suggested that atresia initiation associates with 1) a crosstalk of cell apoptosis, autophagy, and ferroptosis rather than change of typical apoptosis markers, 2) dramatic shift of steroidogenic enzymes, 3) deficient glutathione metabolism, and 4) vascular degeneration. The novel gene candidates and pathways identified in the current study will lead to a comprehensive view of the molecular regulation of ovarian follicular atresia and a new understanding of atresia initiation.

MicroRNA changes through Müller glia dedifferentiation and early/late rod photoreceptor differentiation.

PubMed

Quintero, H; Gómez-Montalvo, A I; Lamas, M

2016-03-01

Cell-type determination is a complex process driven by the combinatorial effect of extrinsic signals and the expression of transcription factors and regulatory genes. MicroRNAs (miRNAs) are non-coding RNAs that, generally, inhibit the expression of target genes and have been involved, among other processes, in cell identity acquisition. To search for candidate miRNAs putatively involved in mice rod photoreceptor and Müller glia (MG) identity, we compared miRNA expression profiles between late-stage retinal progenitor cells (RPCs), CD73-immunopositive (CD73+) rods and postnatal MG. We found a close similarity between RPCs and CD73+ miRNA expression profiles but a divergence between CD73+ and MG miRNA signatures. We validated preferentially expressed miRNAs in the CD73+ subpopulation (miR-182, 183, 124a, 9(∗), 181c and 301b(∗)) or MG (miR-143, 145, 214, 199a-5p, 199b(∗), and 29a). Taking advantage of the unique capacity of MG to dedifferentiate into progenitor-like cells that can be differentiated to a rod phenotype in response to external cues, we evaluated changes of selected miRNAs in MG-derived progenitors (MGDP) during neuronal differentiation. We found decreased levels of miR-143 and 145, but increased levels of miR-29a in MGDP. In MGDPs committed to early neuronal lineages we found increased levels of miR-124a and upregulation of miR-124a, 9(∗) and 181c during MGDP acquisition of rod phenotypes. Furthermore, we demonstrated that ectopic miR-124 expression is sufficient to enhance early neuronal commitment of MGDP. Our data reveal a dynamic regulation of miRNAs in MGDP through early and late neuronal commitment and miRNAs that could be potential targets to exploit the silent neuronal differentiation capacity of MG in mammals. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Identification of nickel response genes in abnormal early developments of sea urchin by differential display polymerase chain reaction.

PubMed

Ryu, Tae Kwon; Lee, Gunsup; Rhee, Yong; Park, Heung-Sik; Chang, Man; Lee, Sukchan; Lee, Jaean; Lee, Taek-Kyun

2012-10-01

Bioassays and biomarkers have been previously developed to assess the effects of heavy metal contaminants on the early life stages of the sea urchin. In this study, malformation in the early developmental processes was observed in sea urchin (Strongylocentrotus intermedius) larvae exposed to 10 ppm Ni for over 30 h. The most critical stage at which the triggering of nickel effects takes place is thought to be the blastula stage, which occurs after fertilization in larval development. To investigate the molecular-level responses of sea urchin exposed to heavy metal stress and to explore the differentially expressed genes that are induced or repressed by nickel, differential display polymerase chain reaction (DD-PCR) was used with sea urchin mRNAs. The malformation-related genes expressed in the early life stages of the sea urchin were cloned from larvae exposed to 10 ppm of nickel for 15 h, and accessed via DD-PCR. Sequence analysis results revealed that each of the genes evidenced high homology with EGF2, PCSK9, serine/threonine protein kinase, apolipophorin precursor protein, and MGC80921 protein/transcript variant 2. This result may prove useful in the development of novel biomarkers for the assessment of heavy metal stresses on sea urchin embryos. Copyright © 2012 Elsevier Inc. All rights reserved.

Differential effect of visual motion adaption upon visual cortical excitability.

PubMed

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

2017-03-01

The objectives of this study were 1 ) to probe the effects of visual motion adaptation on early visual and V5/MT cortical excitability and 2 ) to investigate whether changes in cortical excitability following visual motion adaptation are related to the degree of visual dependency, i.e., an overreliance on visual cues compared with vestibular or proprioceptive cues. Participants were exposed to a roll motion visual stimulus before, during, and after visual motion adaptation. At these stages, 20 transcranial magnetic stimulation (TMS) pulses at phosphene threshold values were applied over early visual and V5/MT cortical areas from which the probability of eliciting a phosphene was calculated. Before and after adaptation, participants aligned the subjective visual vertical in front of the roll motion stimulus as a marker of visual dependency. During adaptation, early visual cortex excitability decreased whereas V5/MT excitability increased. After adaptation, both early visual and V5/MT excitability were increased. The roll motion-induced tilt of the subjective visual vertical (visual dependence) was not influenced by visual motion adaptation and did not correlate with phosphene threshold or visual cortex excitability. We conclude that early visual and V5/MT cortical excitability is differentially affected by visual motion adaptation. Furthermore, excitability in the early or late visual cortex is not associated with an increase in visual reliance during spatial orientation. Our findings complement earlier studies that have probed visual cortical excitability following motion adaptation and highlight the differential role of the early visual cortex and V5/MT in visual motion processing. NEW & NOTEWORTHY We examined the influence of visual motion adaptation on visual cortex excitability and found a differential effect in V1/V2 compared with V5/MT. Changes in visual excitability following motion adaptation were not related to the degree of an individual's visual dependency. Copyright © 2017 the American Physiological Society.

Genetic, morphological, and acoustic evidence reveals lack of diversification in the colonization process in an island bird.

PubMed

Illera, Juan Carlos; Palmero, Ana M; Laiolo, Paola; Rodríguez, Felipe; Moreno, Ángel C; Navascués, Miguel

2014-08-01

Songbirds with recently (i.e., early Holocene) founded populations are suitable models for studying incipient differentiation in oceanic islands. On such systems each colonization event represents a different evolutionary episode that can be studied by addressing sets of diverging phenotypic and genetic traits. We investigate the process of early differentiation in the spectacled warbler (Sylvia conspicillata) in 14 populations separated by sea barriers from three Atlantic archipelagos and from continental regions spanning from tropical to temperate latitudes. Our approach involved the study of sexual acoustic signals, morphology, and genetic data. Mitochondrial DNA did not provide clear population structure. However, microsatellites analyses consistently identified two genetic groups, albeit without correspondence to subspecies classification and little correspondence to geography. Coalescent analyses showed significant evidence for gene flow between the two genetic groups. Discriminant analyses could not correctly assign morphological or acoustic traits to source populations. Therefore, although theory predicting that in isolated populations genetic, morphological, or acoustic traits can lead to radiation, we have strikingly failed to document differentiation on these attributes in a resident passerine throughout three oceanic archipelagos. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Differential Training Facilitates Early Consolidation in Motor Learning

PubMed Central

Henz, Diana; Schöllhorn, Wolfgang I.

2016-01-01

Current research demonstrates increased learning rates in differential learning (DL) compared to repetitive training. To date, little is known on the underlying neurophysiological processes in DL that contribute to superior performance over repetitive practice. In the present study, we measured electroencephalographic (EEG) brain activation patterns after DL and repetitive badminton serve training. Twenty-four semi-professional badminton players performed badminton serves in a DL and repetitive training schedule in a within-subjects design. EEG activity was recorded from 19 electrodes according to the 10–20 system before and immediately after each 20-min exercise. Increased theta activity was obtained in contralateral parieto-occipital regions after DL. Further, increased posterior alpha activity was obtained in DL compared to repetitive training. Results indicate different underlying neuronal processes in DL and repetitive training with a higher involvement of parieto-occipital areas in DL. We argue that DL facilitates early consolidation in motor learning indicated by post-training increases in theta and alpha activity. Further, brain activation patterns indicate somatosensory working memory processes where attentional resources are allocated in processing of somatosensory information in DL. Reinforcing a somatosensory memory trace might explain increased motor learning rates in DL. Finally, this memory trace is more stable against interference from internal and external disturbances that afford executively controlled processing such as attentional processes. PMID:27818627

Accretion, Differentiation, and Impact Processes on the Ureilite Parent Body

NASA Technical Reports Server (NTRS)

Downes, Hilary; Herrin, J. S.; Hudon, P.; Mittlefehldt, D.W.

2007-01-01

Ureilites are primitive ultramafic achondrites composed largely of olivine and pigeonite, with minor augite, orthopyroxene, carbon, sulphide and metal. They represent very early material in the history of the Solar System and (in common with lodranites and acapulcoites) form a bridge between undifferentiated chondrites and fully differentiated asteroidal bodies. They show an intriguing mixture of chemical characteristics, some of which are considered to be nebula-derived (e.g. variations in Delta(sup 17)O and mg#) whereas others have been imposed by asteroidal differentiation (e.g. core formation, silicate partial melting, removal of basalt).

Early In Vitro Differentiation of Mouse Definitive Endoderm Is Not Correlated with Progressive Maturation of Nuclear DNA Methylation Patterns

PubMed Central

Tajbakhsh, Jian; Gertych, Arkadiusz; Fagg, W. Samuel; Hatada, Seigo; Fair, Jeffrey H.

2011-01-01

The genome organization in pluripotent cells undergoing the first steps of differentiation is highly relevant to the reprogramming process in differentiation. Considering this fact, chromatin texture patterns that identify cells at the very early stage of lineage commitment could serve as valuable tools in the selection of optimal cell phenotypes for regenerative medicine applications. Here we report on the first-time use of high-resolution three-dimensional fluorescence imaging and comprehensive topological cell-by-cell analyses with a novel image-cytometrical approach towards the identification of in situ global nuclear DNA methylation patterns in early endodermal differentiation of mouse ES cells (up to day 6), and the correlations of these patterns with a set of putative markers for pluripotency and endodermal commitment, and the epithelial and mesenchymal character of cells. Utilizing this in vitro cell system as a model for assessing the relationship between differentiation and nuclear DNA methylation patterns, we found that differentiating cell populations display an increasing number of cells with a gain in DNA methylation load: first within their euchromatin, then extending into heterochromatic areas of the nucleus, which also results in significant changes of methylcytosine/global DNA codistribution patterns. We were also able to co-visualize and quantify the concomitant stochastic marker expression on a per-cell basis, for which we did not measure any correlation to methylcytosine loads or distribution patterns. We observe that the progression of global DNA methylation is not correlated with the standard transcription factors associated with endodermal development. Further studies are needed to determine whether the progression of global methylation could represent a useful signature of cellular differentiation. This concept of tracking epigenetic progression may prove useful in the selection of cell phenotypes for future regenerative medicine applications. PMID:21779341

Late stages of accumulation and early evolution of the planets

NASA Technical Reports Server (NTRS)

Vityazev, Andrey V.; Perchernikova, G. V.

1991-01-01

Recently developed solutions of problems are discussed that were traditionally considered fundamental in classical solar system cosmogony: determination of planetary orbit distribution patterns, values for mean eccentricity and orbital inclinations of the planets, and rotation periods and rotation axis inclinations of the planets. Two important cosmochemical aspects of accumulation are examined: the time scale for gas loss from the terrestrial planet zone, and the composition of the planets in terms of isotope data. It was concluded that the early beginning of planet differentiation is a function of the heating of protoplanets during collisions with large (thousands of kilometers) bodies. Energetics, heat mass transfer processes, and characteristic time scales of these processes at the early stages of planet evolution are considered.

Differential Effects of Age-of-Acquisition for Concrete Nouns and Action Verbs: Evidence for Partly Distinct Representations?

ERIC Educational Resources Information Center

Boulenger, Veronique; Decoppet, Nathalie; Roy, Alice C.; Paulignan, Yves; Nazir, Tatjana A.

2007-01-01

There is growing evidence that words that are acquired early in life are processed faster and more accurately than words acquired later, even by adults. As neuropsychological and neuroimaging studies have implicated different brain networks in the processing of action verbs and concrete nouns, the present study was aimed at contrasting reaction…

Integrated analysis of miRNA and mRNA expression profiles in tilapia gonads at an early stage of sex differentiation.

PubMed

Tao, Wenjing; Sun, Lina; Shi, Hongjuan; Cheng, Yunying; Jiang, Dongneng; Fu, Beide; Conte, Matthew A; Gammerdinger, William J; Kocher, Thomas D; Wang, Deshou

2016-05-04

MicroRNAs (miRNAs) represent a second regulatory network that has important effects on gene expression and protein translation during biological process. However, the possible role of miRNAs in the early stages of fish sex differentiation is not well understood. In this study, we carried an integrated analysis of miRNA and mRNA expression profiles to explore their possibly regulatory patterns at the critical stage of sex differentiation in tilapia. We identified 279 pre-miRNA genes in tilapia genome, which were highly conserved in other fish species. Based on small RNA library sequencing, we identified 635 mature miRNAs in tilapia gonads, in which 62 and 49 miRNAs showed higher expression in XX and XY gonads, respectively. The predicted targets of these sex-biased miRNAs (e.g., miR-9, miR-21, miR-30a, miR-96, miR-200b, miR-212 and miR-7977) included genes encoding key enzymes in steroidogenic pathways (Cyp11a1, Hsd3b, Cyp19a1a, Hsd11b) and key molecules involved in vertebrate sex differentiation (Foxl2, Amh, Star1, Sf1, Dmrt1, and Gsdf). These genes also showed sex-biased expression in tilapia gonads at 5 dah. Some miRNAs (e.g., miR-96 and miR-737) targeted multiple genes involved in steroid synthesis, suggesting a complex miRNA regulatory network during early sex differentiation in this fish. The sequence and expression patterns of most miRNAs in tilapia are conserved in fishes, indicating the basic functions of vertebrate miRNAs might share a common evolutionary origin. This comprehensive analysis of miRNA and mRNA at the early stage of molecular sex differentiation in tilapia XX and XY gonads lead to the discovery of differentially expressed miRNAs and their putative targets, which will facilitate studies of the regulatory network of molecular sex determination and differentiation in fishes.

Estrogen treatment up-regulates female genes but does not suppress all early testicular markers during rainbow trout male-to-female gonadal transdifferentiation.

PubMed

Vizziano-Cantonnet, Denise; Baron, Daniel; Mahè, Sophie; Cauty, Chantal; Fostier, Alexis; Guiguen, Yann

2008-11-01

In non-mammalian vertebrates, estrogens are key players in ovarian differentiation, but the mechanisms by which they act remain poorly understood. The present study on rainbow trout was designed to investigate whether estrogens trigger the female pathway by activating a group of early female genes (i.e. cyp19a1, foxl2a, foxl2b, fst, bmp4, and fshb) and by repressing early testicular markers (i.e. dmrt1, nr0b1, sox9a1 and sox9a2). Feminization was induced in genetically all-male populations using 17alpha-ethynylestradiol (EE2, 20 mg/kg of food during 2 months). The expression profiles of 100 candidate genes were obtained by real-time RT-PCR and 45 expression profiles displayed a significant differential expression between control populations (males and females) and EE2-treated populations. These expression profiles were grouped in five temporally correlated expression clusters. The estrogen treatment induced most of the early ovarian differentiation genes (foxl2a, foxl2b, fst, bmp4, and fshb) and in particular foxl2a, which was strongly and quickly up-regulated. Simultaneously, Leydig cell genes, involved in androgen synthesis, as well as some Sertoli cell markers (amh, sox9a2) were strongly repressed. However, in contrast to our initial hypothesis, some genes considered as essential for mammalian and fish testis differentiation were not suppressed during the early process of estrogen-induced feminization (dmrt1, nr0b1, sox9a1 and pax2a) and some were even strongly up-regulated (nr0b1, sox9a1and pax2a). In conclusion, estrogens trigger male-to-female transdifferentiation by up-regulating most ovarian specific genes and this up-regulation appears to be crucial for an effective feminization, but estrogens do not concomitantly down-regulate all the testicular differentiation markers.

Differential gene expression during early embryonic development in diapause and non-diapause eggs of multivoltine silkworm Bombyx mori.

PubMed

Ponnuvel, Kangayam M; Murthy, Geetha N; Awasthi, Arvind K; Rao, Guruprasad; Vijayaprakash, Nanjappa B

2010-11-01

Quantification of the differential expression of metabolic enzyme and heat-shock protein genes (Hsp) during early embryogenesis in diapause and non-diapause eggs of the silkworm B. mori was carried out by semi-quantitative RT-PCR. Data analysis revealed that, the phosphofructokinase (PFK) expression started at a higher level in the early stage (6 h after oviposition) in non-diapause eggs, while in diapause induced eggs, it started at a lower level. However, the PFK gene expression in diapause eggs was comparatively higher than in non-diapause eggs. PFK facilitates use of carbohydrate reserves. The lower level of PFK gene expression in the early stage of diapause induced eggs but comparatively higher level of expression than in non-diapause eggs is due to enzyme inactivation via protein phosphorylation during early embryogenesis followed by de-phosphorylation in later stage. The sorbitol dehydrogenase-2 (SDH-2) gene was down regulated in diapause induced eggs up to 24 h and its expression levels in diapause induced eggs coincided with that of PFK gene at 48h in non-diapause eggs. During carbohydrate metabolism, there is an initial temporary accumulation of sorbitol which acts as protectant. The down regulation of SDH-2 gene during the first 24 hours in diapause induced eggs was due to the requirement of sorbitol as protectant. However, since the diapause process culminates by 48 h, the SDH-2 gene expression increased and coincided with that of PFK gene expression. The trehalase (Tre) gene expression was at a lower level in diapause induced eggs compared to non-diapausing eggs. The induction of Tre activity is to regulate uptake and use of sugar by the tissues. The non-diapause eggs revealed maximum expression of GPase gene with major fluctuations as well as an overall higher expression compared to diapause induced eggs. The diapause process requires less energy source which reflects lower activity of the gene. Heat shock protein (Hsp) genes (Hsp20.4, 40, 70, and 90) revealed differential levels of expression in both the eggs at all stages of embryonic development. The present study thus provides an overview of the differential expression levels of metabolic enzyme and Hsp genes in non-diapause and diapause induced eggs of multivoltine silkworm B. mori within 48 h after oviposition, confirming the major role of in early embryogenesis.

Differentiating Hydrothermal, Pedogenic, and Glacial Weathering in a Cold Volcanic Mars-Analog Environment

NASA Technical Reports Server (NTRS)

Scudder, N. A.; Horgan, B.; Havig, J.; Rutledge, A.; Rampe, E. B.; Hamilton, T.

2016-01-01

Although the current cold, dry environment of Mars extends back through much of its history, its earliest periods experienced significant water- related surface activity. Both geomorphic features (e.g., paleolakes, deltas, and river valleys) and hydrous mineral detections (e.g., clays and salts) have historically been interpreted to imply a "warm and wet" early Mars climate. More recently, atmospheric modeling studies have struggled to produce early climate conditions with temperatures above 0degC, leading some studies to propose a "cold and icy" early Mars dominated by widespread glaciation with transient melting. However, the alteration mineralogy produced in subglacial environments is not well understood, so the extent to which cold climate glacial weathering can produce the diverse alteration mineralogy observed on Mars is unknown. This summer, we will be conducting a field campaign in a glacial weathering environment in the Cascade Range, OR in order to determine the types of minerals that these environments produce. However, we must first disentangle the effects of glacial weathering from other significant alteration processes. Here we attempt a first understanding of glacial weathering by differentiating rocks and sediments weathered by hydrothermal, pedogenic, and glacial weathering processes in the Cascades volcanic range.

The small molecule Mek1/2 inhibitor U0126 disrupts the chordamesoderm to notochord transition in zebrafish.

PubMed

Hawkins, Thomas A; Cavodeassi, Florencia; Erdélyi, Ferenc; Szabó, Gábor; Lele, Zsolt

2008-04-17

Key molecules involved in notochord differentiation and function have been identified through genetic analysis in zebrafish and mice, but MEK1 and 2 have so far not been implicated in this process due to early lethality (Mek1-/-) and functional redundancy (Mek2-/-) in the knockout animals. Here, we reveal a potential role for Mek1/2 during notochord development by using the small molecule Mek1/2 inhibitor U0126 which blocks phosphorylation of the Mek1/2 target gene Erk1/2 in vivo. Applying the inhibitor from early gastrulation until the 18-somite stage produces a specific and consistent phenotype with lack of dark pigmentation, shorter tail and an abnormal, undulated notochord. Using morphological analysis, in situ hybridization, immunhistochemistry, TUNEL staining and electron microscopy, we demonstrate that in treated embryos the chordamesoderm to notochord transition is disrupted and identify disorganization in the medial layer of the perinotochordal basement mebrane as the probable cause of the undulations and bulges in the notochord. We also examined and excluded FGF as the upstream signal during this process. Using the small chemical U0126, we have established a novel link between MAPK-signaling and notochord differentiation. Our phenotypic analysis suggests a potential connection between the MAPK-pathway, the COPI-mediated intracellular transport and/or the copper-dependent posttranslational regulatory processes during notochord differentiation.

Equivalent mismatch negativity deficits across deviant types in early illness schizophrenia-spectrum patients.

PubMed

Hay, Rachel A; Roach, Brian J; Srihari, Vinod H; Woods, Scott W; Ford, Judith M; Mathalon, Daniel H

2015-02-01

Neurophysiological abnormalities in auditory deviance processing, as reflected by the mismatch negativity (MMN), have been observed across the course of schizophrenia. Studies in early schizophrenia patients have typically shown varying degrees of MMN amplitude reduction for different deviant types, suggesting that different auditory deviants are uniquely processed and may be differentially affected by duration of illness. To explore this further, we examined the MMN response to 4 auditory deviants (duration, frequency, duration+frequency "double deviant", and intensity) in 24 schizophrenia-spectrum patients early in the illness (ESZ) and 21 healthy controls. ESZ showed significantly reduced MMN relative to healthy controls for all deviant types (p<0.05), with no significant interaction with deviant type. No correlations with clinical symptoms were present (all ps>0.05). These findings support the conclusion that neurophysiological mechanisms underlying processing of auditory deviants are compromised early in illness, and these deficiencies are not specific to the type of deviant presented. Copyright © 2015 Elsevier B.V. All rights reserved.

The Activity of Differentiation Factors Induces Apoptosis in Polyomavirus Large T-Expressing Myoblasts

PubMed Central

Fimia, Gian Maria; Gottifredi, Vanesa; Bellei, Barbara; Ricciardi, Maria Rosaria; Tafuri, Agostino; Amati, Paolo; Maione, Rossella

1998-01-01

It is commonly accepted that pathways that regulate proliferation/differentiation processes, if altered in their normal interplay, can lead to the induction of programmed cell death. In a previous work we reported that Polyoma virus Large Tumor antigen (PyLT) interferes with in vitro terminal differentiation of skeletal myoblasts by binding and inactivating the retinoblastoma antioncogene product. This inhibition occurs after the activation of some early steps of the myogenic program. In the present work we report that myoblasts expressing wild-type PyLT, when subjected to differentiation stimuli, undergo cell death and that this cell death can be defined as apoptosis. Apoptosis in PyLT-expressing myoblasts starts after growth factors removal, is promoted by cell confluence, and is temporally correlated with the expression of early markers of myogenic differentiation. The block of the initial events of myogenesis by transforming growth factor β or basic fibroblast growth factor prevents PyLT-induced apoptosis, while the acceleration of this process by the overexpression of the muscle-regulatory factor MyoD further increases cell death in this system. MyoD can induce PyLT-expressing myoblasts to accumulate RB, p21, and muscle- specific genes but is unable to induce G00 arrest. Several markers of different phases of the cell cycle, such as cyclin A, cdk-2, and cdc-2, fail to be down-regulated, indicating the occurrence of cell cycle progression. It has been frequently suggested that apoptosis can result from an unbalanced cell cycle progression in the presence of a contrasting signal, such as growth factor deprivation. Our data involve differentiation pathways, as a further contrasting signal, in the generation of this conflict during myoblast cell apoptosis. PMID:9614186

The neuroregenerative mechanism mediated by the Hsp90-binding immunophilin FKBP52 resembles the early steps of neuronal differentiation

PubMed Central

Quintá, HR; Galigniana, MD

2012-01-01

BACKGROUND AND PURPOSE The immunosuppressive macrolide FK506 (tacrolimus) shows neuroregenerative action by a mechanism that appears to involve the Hsp90-binding immunophilin FKBP52. This study analyses some aspects of the early steps of neuronal differentiation and neuroregeneration. EXPERIMENTAL APPROACH Undifferentiated murine neuroblastoma cells and hippocampal neurones isolated from embryonic day-17 rat embryos were induced to differentiate with FK506. Subcellular relocalization of FKBP52, Hsp90 and its co-chaperone p23 was analysed by indirect immunofluorescence confocal microscopy and by Western blots of axonal fractions isolated from cells grown on a porous transwell cell culture chamber. Neuroregeneration was evaluated using a scratch-wound assay. KEY RESULTS In undifferentiated cells, FKBP52, Hsp90 and p23 are located in the cell nucleus, forming an annular structure that disassembles when the differentiation process is triggered by FK506. This was observed in the N2a cell line and in hippocampal neurones. More importantly, the annular structure of chaperones is reassembled after damaging the neurones, whereas FK506 prompts their rapid regeneration, a process linked to the subcellular redistribution of the heterocomplex. CONCLUSIONS AND IMPLICATIONS There is a direct relationship between the disassembly of the chaperone complex and the progression of neuronal differentiation upon stimulation with the immunophilin ligand FK506. Both neuronal differentiation and neuroregeneration appear to be mechanistically linked, so the elucidation of one mechanism may lead to unravel the properties of the other. This study also implies that the discovery of FK506 derivatives, devoid of immunosuppressive action, would be therapeutically significant for neurotrophic use. PMID:22091865

Murine Mesenchymal Stem Cell Commitment to Differentiation is Regulated by Mitochondrial Dynamics

PubMed Central

Forni, Maria Fernanda; Peloggia, Julia; Trudeau, Kyle; Shirihai, Orian; Kowaltowski, Alicia J.

2015-01-01

Mouse skin mesenchymal stem cells (msMSCs) are dermis CD105+CD90+CD73+CD29+CD34− mesodermal precursors which, after in vitro induction, undergo chondro, adipo and osteogenesis. Extensive metabolic reconfiguration has been found to occur during differentiation, and the bioenergetic status of a cell is known to be dependent on the quality and abundance of the mitochondrial population, which may be regulated by fusion and fission. However, little is known regarding the impact of mitochondrial dynamics on the differentiation process. We addressed this knowledge gap by isolating MSCs from Swiss female mice, inducing these cells to differentiate into osteo, chondro and adipocytes and measuring changes in mass, morphology, dynamics and bioenergetics. Mitochondrial biogenesis was increased in adipogenesis, as evaluated through confocal microscopy, citrate synthase activity and mtDNA content. The early steps of adipo and osteogenesis involved mitochondrial elongation, as well as increased expression of mitochondrial fusion proteins Mfn1 and 2. Chondrogenesis involved a fragmented mitochondrial phenotype, increased expression of fission proteins Drp1, Fis1 and 2 and enhanced mitophagy. These events were accompanied by profound bioenergetic alterations during the commitment period. Moreover, knockdown of Mfn2 in adipo and osteogenesis and the overexpression of a dominant negative form of Drp1 during chondrogenesis resulted in a loss of differentiation ability. Overall, we find that mitochondrial morphology and its regulating processes of fission/fusion are modulated early on during commitment, leading to alterations in the bioenergetic profile that are important for differentiation. We thus propose a central role for mitochondrial dynamics in the maintenance/commitment of mesenchymal stem cells. PMID:26638184

[Rehabilitative measures in hearing-impaired children].

PubMed

von Wedel, H; von Wedel, U C; Zorowka, P

1991-12-01

On the basis of certain fundamental data on the maturation processes of the central auditory pathways in early childhood the importance of early intervention with hearing aids is discussed and emphasized. Pathological hearing, that is acoustical deprivation in early childhood will influence the maturation process. Very often speech development is delayed if diagnosis and therapy or rehabilitation are not early enough. Anamnesis, early diagnosis and clinical differential diagnosis are required before a hearing aid can be fitted. Selection criteria and adjustment parameters are discussed, showing that the hearing aid fitting procedure must be embedded in a complex matrix of requirements related to the development of speech as well as to the cognitive, emotional and social development of the child. As a rule, finding and preparing the "best" hearing aids (binaural fitting is obligatory) for a child is a long and often difficult process, which can only be performed by specialists who are pedo-audiologists. After the binaural fitting of hearing aids an intensive hearing and speech education in close cooperation between parents, pedo-audiologist and teacher must support the whole development of the child.

The transcriptional landscape of αβ T cell differentiation

PubMed Central

Mingueneau, Michael; Kreslavsky, Taras; Gray, Daniel; Heng, Tracy; Cruse, Richard; Ericson, Jeffrey; Bendall, Sean; Spitzer, Matt; Nolan, Garry; Kobayashi, Koichi; von Boehmer, Harald; Mathis, Diane; Benoist, Christophe

2013-01-01

αβT cell differentiation from thymic precursors is a complex process, explored here with the breadth of ImmGen expression datasets, analyzing how differentiation of thymic precursors gives rise to transcriptomes. After surprisingly gradual changes though early T commitment, transit through the CD4+CD8+ stage involves a shutdown or rare breadth, and correlating tightly with MYC. MHC-driven selection promotes a large-scale transcriptional reactivation. We identify distinct signatures that mark cells destined for positive selection versus apoptotic deletion. Differential expression of surprisingly few genes accompany CD4 or CD8 commitment, a similarity that carries through to peripheral T cells and their activation, revealed by mass cytometry phosphoproteomics. The novel transcripts identified as candidate mediators of key transitions help define the “known unknown” of thymocyte differentiation. PMID:23644507

Differential Network Analyses of Alzheimer’s Disease Identify Early Events in Alzheimer’s Disease Pathology

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

Xia, Jing; Rocke, David M.; Perry, George

In late-onset Alzheimer’s disease (AD), multiple brain regions are not affected simultaneously. Comparing the gene expression of the affected regions to identify the differences in the biological processes perturbed can lead to greater insight into AD pathogenesis and early characteristics. We identified differentially expressed (DE) genes from single cell microarray data of four AD affected brain regions: entorhinal cortex (EC), hippocampus (HIP), posterior cingulate cortex (PCC), and middle temporal gyrus (MTG). We organized the DE genes in the four brain regions into region-specific gene coexpression networks. Differential neighborhood analyses in the coexpression networks were performed to identify genes with lowmore » topological overlap (TO) of their direct neighbors. The low TO genes were used to characterize the biological differences between two regions. Our analyses show that increased oxidative stress, along with alterations in lipid metabolism in neurons, may be some of the very early events occurring in AD pathology. Cellular defense mechanisms try to intervene but fail, finally resulting in AD pathology as the disease progresses. Furthermore, disease annotation of the low TO genes in two independent protein interaction networks has resulted in association between cancer, diabetes, renal diseases, and cardiovascular diseases.« less

Differential Network Analyses of Alzheimer’s Disease Identify Early Events in Alzheimer’s Disease Pathology

DOE PAGES

Xia, Jing; Rocke, David M.; Perry, George; ...

2014-01-01

In late-onset Alzheimer’s disease (AD), multiple brain regions are not affected simultaneously. Comparing the gene expression of the affected regions to identify the differences in the biological processes perturbed can lead to greater insight into AD pathogenesis and early characteristics. We identified differentially expressed (DE) genes from single cell microarray data of four AD affected brain regions: entorhinal cortex (EC), hippocampus (HIP), posterior cingulate cortex (PCC), and middle temporal gyrus (MTG). We organized the DE genes in the four brain regions into region-specific gene coexpression networks. Differential neighborhood analyses in the coexpression networks were performed to identify genes with lowmore » topological overlap (TO) of their direct neighbors. The low TO genes were used to characterize the biological differences between two regions. Our analyses show that increased oxidative stress, along with alterations in lipid metabolism in neurons, may be some of the very early events occurring in AD pathology. Cellular defense mechanisms try to intervene but fail, finally resulting in AD pathology as the disease progresses. Furthermore, disease annotation of the low TO genes in two independent protein interaction networks has resulted in association between cancer, diabetes, renal diseases, and cardiovascular diseases.« less

Differential processing of part-to-whole and part-to-part face priming: an ERP study.

PubMed

Jemel, B; George, N; Chaby, L; Fiori, N; Renault, B

1999-04-06

We provide electrophysiological evidence supporting the hypothesis that part and whole face processing involve distinct functional mechanisms. We used a congruency judgment task and studied part-to-whole and part-to-part priming effects. Neither part-to-whole nor part-to-part conditions elicited early congruency effects on face-specific ERP components, suggesting that activation of the internal representations should occur later on. However, these components showed differential responsiveness to whole faces and isolated eyes. In addition, although late ERP components were affected when the eye targets were not associated with the prime in both conditions, their temporal and topographical features depended on the latter. These differential effects suggest the existence of distributed neural networks in the inferior temporal cortex where part and whole facial representations may be stored.

Biased gene expression in early honeybee larval development

PubMed Central

2013-01-01

Background Female larvae of the honeybee (Apis mellifera) develop into either queens or workers depending on nutrition. This nutritional stimulus triggers different developmental trajectories, resulting in adults that differ from each other in physiology, behaviour and life span. Results To understand how these trajectories are established we have generated a comprehensive atlas of gene expression throughout larval development. We found substantial differences in gene expression between worker and queen-destined larvae at 6 hours after hatching. Some of these early changes in gene expression are maintained throughout larval development, indicating that caste-specific developmental trajectories are established much earlier than previously thought. Within our gene expression data we identified processes that potentially underlie caste differentiation. Queen-destined larvae have higher expression of genes involved in transcription, translation and protein folding early in development with a later switch to genes involved in energy generation. Using RNA interference, we were able to demonstrate that one of these genes, hexamerin 70b, has a role in caste differentiation. Both queen and worker developmental trajectories are associated with the expression of genes that have alternative splice variants, although only a single variant of a gene tends to be differentially expressed in a given caste. Conclusions Our data, based on the biases in gene expression early in development together with published data, supports the idea that caste development in the honeybee consists of two phases; an initial biased phase of development, where larvae can still switch to the other caste by differential feeding, followed by commitment to a particular developmental trajectory. PMID:24350621

Effects of Leucine Supplementation and Serum Withdrawal on Branched-Chain Amino Acid Pathway Gene and Protein Expression in Mouse Adipocytes

PubMed Central

Vivar, Juan C.; Knight, Megan S.; Pointer, Mildred A.; Gwathmey, Judith K.; Ghosh, Sujoy

2014-01-01

The essential branched-chain amino acids (BCAA), leucine, valine and isoleucine, are traditionally associated with skeletal muscle growth and maintenance, energy production, and generation of neurotransmitter and gluconeogenic precursors. Recent evidence from human and animal model studies has established an additional link between BCAA levels and obesity. However, details of the mechanism of regulation of BCAA metabolism during adipogenesis are largely unknown. We interrogated whether the expression of genes and proteins involved in BCAA metabolism are sensitive to the adipocyte differentiation process, and responsive to nutrient stress from starvation or BCAA excess. Murine 3T3-L1 preadipocytes were differentiated to adipocytes under control conditions and under conditions of L-leucine supplementation or serum withdrawal. RNA and proteins were isolated at days 0, 4 and 10 of differentiation to represent pre-differentiation, early differentiation and late differentiation stages. Expression of 16 BCAA metabolism genes was quantified by quantitative real-time PCR. Expression of the protein levels of branched-chain amino acid transaminase 2 (Bcat2) and branched-chain alpha keto acid dehydrogenase (Bckdha) was quantified by immunoblotting. Under control conditions, all genes displayed induction of gene expression during early adipogenesis (Day 4) compared to Day 0. Leucine supplementation resulted in an induction of Bcat2 and Bckdha genes during early and late differentiation. Western blot analysis demonstrated condition-specific concordance between gene and protein expression. Serum withdrawal resulted in undetectable Bcat2 and Bckdha protein levels at all timepoints. These results demonstrate that the expression of genes related to BCAA metabolism are regulated during adipocyte differentiation and influenced by nutrient levels. These results provide additional insights on how BCAA metabolism is associated with adipose tissue function and extends our understanding of the transcriptomic response of this pathway to variations in nutrient availability. PMID:25050624

Processing α-mercuric iodide by zone refining

NASA Astrophysics Data System (ADS)

Burger, A.; Morgan, S. H.; Henderson, D. O.; Biao, Y.; Zhang, K.; Silberman, E.; Nason, D.; van den Berg, L.; Ortale-Baccash, C.; Cross, E.

1993-03-01

An investigation is being conducted on zone refining α-mercuric iodide. Analytical studies using differential scanning calorimetry and anion chromatography indicate that impurities are accumulated mainly at the end where zone travel terminates. Early results indicate that single crystals can be readily grown from zone-refined material.

Keep on growing: building and patterning leaves in the grasses

USDA-ARS?s Scientific Manuscript database

Monocot leaves have unique features that arise early in their development. Maturing leaves protectively enclose younger leaves and the meristem, the pool of founder cells from which a leaf emerges. Through the maturation process, proximal sheath and distal blade tissues differentiate and are separat...

Early Thermal History of Rhea: The Role of Serpentinization and Liquid State Convection

NASA Astrophysics Data System (ADS)

Czechowski, Leszek; Łosiak, Anna

2016-12-01

Early thermal history of Rhea is investigated. The role of the following parameters of the model is investigated: time of beginning of accretion, tini, duration of accretion, tac, viscosity of ice close to the melting point, η0, activation energy in the formula for viscosity, E, thermal conductivity of silicate component, ksil, ammonia content, XNH3, and energy of serpentinization, cserp. We found that tini and tac are crucial for evolution. All other parameters are also important, but no dramatic differences are found for realistic values. The process of differentiation is also investigated. It is found that liquid state convection could delay the differentiation for hundreds of My. The results are confronted with observational data from Cassini spacecraft. It is possible that differentiation is fully completed but the density of formed core is close to the mean density. If this interpretation is correct, then Rhea could have accreted any time before 3-4 My after formation of CAI.

Differential MicroRNA Analyses of Burkholderia pseudomallei- and Francisella tularensis-Exposed hPBMCs Reveal Potential Biomarkers.

PubMed

Cer, Regina Z; Herrera-Galeano, J Enrique; Frey, Kenneth G; Schully, Kevin L; Luu, Truong V; Pesce, John; Mokashi, Vishwesh P; Keane-Myers, Andrea M; Bishop-Lilly, Kimberly A

2017-01-01

Increasing evidence that microRNAs (miRNAs) play important roles in the immune response against infectious agents suggests that miRNA might be exploitable as signatures of exposure to specific infectious agents. In order to identify potential early miRNA biomarkers of bacterial infections, human peripheral blood mononuclear cells (hPBMCs) were exposed to two select agents, Burkholderia pseudomallei K96243 and Francisella tularensis SHU S4, as well as to the nonpathogenic control Escherichia coli DH5 α . RNA samples were harvested at three early time points, 30, 60, and 120 minutes postexposure, then sequenced. RNAseq analyses identified 87 miRNAs to be differentially expressed (DE) in a linear fashion. Of these, 31 miRNAs were tested using the miScript miRNA qPCR assay. Through RNAseq identification and qPCR validation, we identified differentially expressed miRNA species that may be involved in the early response to bacterial infections. Based upon its upregulation at early time points postexposure in two different individuals, hsa-mir-30c-5p is a miRNA species that could be studied further as a potential biomarker for exposure to these gram-negative intracellular pathogens. Gene ontology functional analyses demonstrated that programmed cell death is the first ranking biological process associated with miRNAs that are upregulated in F. tularensis -exposed hPBMCs.

Differential MicroRNA Analyses of Burkholderia pseudomallei- and Francisella tularensis-Exposed hPBMCs Reveal Potential Biomarkers

PubMed Central

Herrera-Galeano, J. Enrique; Frey, Kenneth G.; Schully, Kevin L.; Luu, Truong V.; Pesce, John; Mokashi, Vishwesh P.; Keane-Myers, Andrea M.; Bishop-Lilly, Kimberly A.

2017-01-01

Increasing evidence that microRNAs (miRNAs) play important roles in the immune response against infectious agents suggests that miRNA might be exploitable as signatures of exposure to specific infectious agents. In order to identify potential early miRNA biomarkers of bacterial infections, human peripheral blood mononuclear cells (hPBMCs) were exposed to two select agents, Burkholderia pseudomallei K96243 and Francisella tularensis SHU S4, as well as to the nonpathogenic control Escherichia coli DH5α. RNA samples were harvested at three early time points, 30, 60, and 120 minutes postexposure, then sequenced. RNAseq analyses identified 87 miRNAs to be differentially expressed (DE) in a linear fashion. Of these, 31 miRNAs were tested using the miScript miRNA qPCR assay. Through RNAseq identification and qPCR validation, we identified differentially expressed miRNA species that may be involved in the early response to bacterial infections. Based upon its upregulation at early time points postexposure in two different individuals, hsa-mir-30c-5p is a miRNA species that could be studied further as a potential biomarker for exposure to these gram-negative intracellular pathogens. Gene ontology functional analyses demonstrated that programmed cell death is the first ranking biological process associated with miRNAs that are upregulated in F. tularensis-exposed hPBMCs. PMID:28791299

Heavy metal tolerance in plants: A model evolutionary system.

PubMed

Macnair, M R

1987-12-01

Evolved tolerance to toxic concentrations of heavy metals in plants inhabiting spoil heaps of mines is a well known phenomenon that has been the subject of much research in the last two decades. These plants are useful models for studying processes involved in the early stages of the speciation of edaphic endemics. Recent work has revealed the importance of several phenomena in the differentiation of tolerant populations, including natural selection, founder effects and 'hitch-hiking', and has demonstrated the early evolution of morphological differentiation and reproductive isolating mechanisms. Further studies of the biochemistry and molecular biology of heavy metal tolerance will help to show why some plant groups, such as Agrostis, are far more prone to evolve tolerance than others. Copyright © 1987. Published by Elsevier Ltd.

The differentiation history of the terrestrial planets as recorded on the moon

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

Borg, L

2007-02-20

The outline for this report is: (1) Factors Leading to Lunar Magma Ocean Model for Planetary Differentiation (2) Rationale for Magma Oceans on Other Planets Means for early efficient differentiation (Works on Moon why not here?) (3) Some Inconsistencies between the Lunar Magma Ocean Model and Observations. The conclusions are: (1) Differentiation via solidification of a magma ocean is derived from geologic observations of the Moon (2) Although geologic observations on other bodies are often consistent with differentiation via magma ocean solidification, it is not generally required. (3) There are some fundamental inconsistencies between observed lunar data and the model,more » that will require this model to be modified (4) Nevertheless, the Moon is the only location we know of to study magma ocean process in detail.« less

Antiadipogenic effects of subthermal electric stimulation at 448 kHz on differentiating human mesenchymal stem cells

PubMed Central

HERNÁNDEZ-BULE, MARÍA LUISA; MARTÍNEZ-BOTAS, JAVIER; TRILLO, MARÍA ÁNGELES; PAÍNO, CARLOS L; ÚBEDA, ALEJANDRO

2016-01-01

The 448 kHz capacitive-resistive electric transfer (CRET) is an electrothermal therapy currently applied in anticellulite and antiobesity treatments. The aim of the present study was to determine whether exposure to the CRET electric signal at subthermal doses affected early adipogenic processes in adipose-derived stem cells (ADSC) from human donors. ADSC were incubated for 2 or 9 days in the presence of adipogenic medium, and exposed or sham-exposed to 5 min pulses of 448 kHz electric signal at 50 µA/mm2 during the last 48 h of the incubation. Colorimetric, immunofluorescence, western blotting and reverse transcription-quantitative polymerase chain reaction assays were performed to assess adipogenic differentiation of the ADSC. Electric stimulation significantly decreased cytoplasmic lipid content, after both 2 and 9 days of differentiation. The antiadipogenic response in the 9 day samples was accompanied by activation of mitogen-activated protein kinase kinase 1/2, decreased expression and partial inactivation of peroxisome proliferator-activated receptor (PPAR) γ, which was translocated from the nucleus to the cytoplasm, together with a significant decrease in the expression levels of the PPARG1 gene, perilipin, angiopoietin-like protein 4 and fatty acid synthase. These results demonstrated that subthermal stimulation with CRET interferes with the early adipogenic differentiation in ADSC, indicating that the electric stimulus itself can modulate processes controlling the synthesis and mobilization of fat, even in the absence of the concomitant thermal and mechanical components of the thermoelectric therapy CRET. PMID:27035334

The Evaluation and Research of Multi-Project Programs: Program Component Analysis.

ERIC Educational Resources Information Center

Baker, Eva L.

1977-01-01

It is difficult to base evaluations on concepts irrelevant to state policy making. Evaluation of a multiproject program requires both time and differentiation of method. Data from the California Early Childhood Program illustrate process variables for program component analysis, and research questions for intraprogram comparison. (CP)

Environmental isolation task

NASA Technical Reports Server (NTRS)

Coulbert, C. D.

1982-01-01

The failure-analysis process was organized into a more specific set of long-term degradation steps so that material property change can be differentiated from module damage and module failure. Increasing module performance and life are discussed. A polymeric aging computer model is discussed. Early detection of polymer surface reactions due to aging is reported.

The (146,147)Sm-(142,143)Nd systematics of early terrestrial differentiation and the lost continents of the early Earth

NASA Technical Reports Server (NTRS)

Harper, Charles L., Jr.; Jacobsen, Stein B.

1992-01-01

The very early history of the Earth has been one of the great enduring puzzles in the history of geology. We report evidence which clearly can be described as a vestige of a beginning, because the evidence that we report cannot be interpreted in any other way except as a geochemical signal of processes active in the very early history of the Earth. The evidence itself is a very small anomaly in the abundance of SM-146. The primary aims of this study were to: (1) verify the existence of the 'lost continents' of the Hadean era; and (2) determine their mean age.

The Potential of Gait Analysis to Contribute to Differential Diagnosis of Early Stage Dementia: Current Research and Future Directions

ERIC Educational Resources Information Center

Morgan, Debra; Funk, Melanie; Crossley, Margaret; Basran, Jenny; Kirk, Andrew; Bello-Haas, Vanina Dal

2007-01-01

Early differential diagnosis of dementia is becoming increasingly important as new pharmacologic therapies are developed, as these treatments are not equally effective for all types of dementia. Early detection and differential diagnosis also facilitates informed family decision making and timely access to appropriate services. Information about…

In vitro long-term development of cultured inner ear stem cells of newborn rat.

PubMed

Carricondo, Francisco; Iglesias, Mari Cruz; Rodríguez, Fernando; Poch-Broto, Joaquin; Gil-Loyzaga, Pablo

2010-10-01

The adult mammalian auditory receptor lacks any ability to repair and/or regenerate after injury. However, the late developing cochlea still contains some stem-cell-like elements that might be used to regenerate damaged neurons and/or cells of the organ of Corti. Before their use in any application, stem cell numbers need to be amplified because they are usually rare in late developing and adult tissues. The numerous re-explant cultures required for the progressive amplification process can result in a spontaneous differentiation process. This aspect has been implicated in the tumorigenicity of stem cells when transplanted into a tissue. The aim of this study has been to determine whether cochlear stem cells can proliferate and differentiate spontaneously in long-term cultures without the addition of any factor that might influence these processes. Cochlear stem cells, which express nestin protein, were cultured in monolayers and fed with DMEM containing 5% FBS. They quickly organized themselves into typical spheres exhibiting a high proliferation rate, self-renewal property, and differentiation ability. Secondary cultures of these stem cell spheres spontaneously differentiated into neuroectodermal-like cells. The expression of nestin, glial-fibrillary-acidic protein, vimentin, and neurofilaments was evaluated to identify early differentiation. Nestin expression appeared in primary and secondary cultures. Other markers were also identified in differentiating cells. Further research might demonstrate the spontaneous differentiation of cochlear stem cells and their teratogenic probability when they are used for transplantation.

Altered gene expression in dry age-related macular degeneration suggests early loss of choroidal endothelial cells.

PubMed

Whitmore, S Scott; Braun, Terry A; Skeie, Jessica M; Haas, Christine M; Sohn, Elliott H; Stone, Edwin M; Scheetz, Todd E; Mullins, Robert F

2013-01-01

Age-related macular degeneration (AMD) is a major cause of blindness in developed countries. The molecular pathogenesis of early events in AMD is poorly understood. We investigated differential gene expression in samples of human retinal pigment epithelium (RPE) and choroid from early AMD and control maculas with exon-based arrays. Gene expression levels in nine human donor eyes with early AMD and nine control human donor eyes were assessed using Affymetrix Human Exon ST 1.0 arrays. Two controls did not pass quality control and were removed. Differentially expressed genes were annotated using the Database for Annotation, Visualization and Integrated Discovery (DAVID), and gene set enrichment analysis (GSEA) was performed on RPE-specific and endothelium-associated gene sets. The complement factor H (CFH) genotype was also assessed, and differential expression was analyzed regarding high AMD risk (YH/HH) and low AMD risk (YY) genotypes. Seventy-five genes were identified as differentially expressed (raw p value <0.01; ≥50% fold change, mean log2 expression level in AMD or control ≥ median of all average gene expression values); however, no genes were significant (adj. p value <0.01) after correction for multiple hypothesis testing. Of 52 genes with decreased expression in AMD (fold change <0.5; raw p value <0.01), 18 genes were identified by DAVID analysis as associated with vision or neurologic processes. The GSEA of the RPE-associated and endothelium-associated genes revealed a significant decrease in genes typically expressed by endothelial cells in the early AMD group compared to controls, consistent with previous histologic and proteomic studies. Analysis of the CFH genotype indicated decreased expression of ADAMTS9 in eyes with high-risk genotypes (fold change = -2.61; raw p value=0.0008). GSEA results suggest that RPE transcripts are preserved or elevated in early AMD, concomitant with loss of endothelial cell marker expression. These results are consistent with the notion that choroidal endothelial cell dropout or dedifferentiation occurs early in the pathogenesis of AMD.

A Review of Recent Studies on Differential Reinforcement during Skill Acquisition in Early Intervention

ERIC Educational Resources Information Center

Vladescu, Jason C.; Kodak, Tiffany

2010-01-01

Although the use of differential reinforcement has been recommended in previous investigations and in early intervention curriculum manuals, few studies have evaluated the best method for providing differential reinforcement to maximize independent responding. This paper reviews previous research on the effectiveness of differential reinforcement…

Determination of Stability and Control Derivatives using Computational Fluid Dynamics and Automatic Differentiation

NASA Technical Reports Server (NTRS)

Park, Michael A.; Green, Lawrence L.; Montgomery, Raymond C.; Raney, David L.

1999-01-01

With the recent interest in novel control effectors there is a need to determine the stability and control derivatives of new aircraft configurations early in the design process. These derivatives are central to most control law design methods and would allow the determination of closed-loop control performance of the vehicle. Early determination of the static and dynamic behavior of an aircraft may permit significant improvement in configuration weight, cost, stealth, and performance through multidisciplinary design. The classical method of determining static stability and control derivatives - constructing and testing wind tunnel models - is expensive and requires a long lead time for the resultant data. Wind tunnel tests are also limited to the preselected control effectors of the model. To overcome these shortcomings, computational fluid dynamics (CFD) solvers are augmented via automatic differentiation, to directly calculate the stability and control derivatives. The CFD forces and moments are differentiated with respect to angle of attack, angle of sideslip, and aircraft shape parameters to form these derivatives. A subset of static stability and control derivatives of a tailless aircraft concept have been computed by two differentiated inviscid CFD codes and verified for accuracy with central finite-difference approximations and favorable comparisons to a simulation database.

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.

Early Planetary Differentiation: Comparative Planetology

NASA Technical Reports Server (NTRS)

Jones, John H.

2006-01-01

We currently have extensive data for four different terrestrial bodies of the inner solar system: Earth, the Moon, Mars, and the Eucrite Parent Body [EPB]. All formed early cores; but all(?) have mantles with elevated concentrations of highly sidero-phile elements, suggestive of the addition of a late "veneer". Two appear to have undergone extensive differentiation consistent with a global magma ocean. One appears to be inconsistent with a simple model of "low-pressure" chondritic differentiation. Thus, there seems to be no single, simple paradigm for understand-ing early differentiation.

A data analysis framework for biomedical big data: Application on mesoderm differentiation of human pluripotent stem cells

PubMed Central

Karlsson, Alexander; Riveiro, Maria; Améen, Caroline; Åkesson, Karolina; Andersson, Christian X.; Sartipy, Peter; Synnergren, Jane

2017-01-01

The development of high-throughput biomolecular technologies has resulted in generation of vast omics data at an unprecedented rate. This is transforming biomedical research into a big data discipline, where the main challenges relate to the analysis and interpretation of data into new biological knowledge. The aim of this study was to develop a framework for biomedical big data analytics, and apply it for analyzing transcriptomics time series data from early differentiation of human pluripotent stem cells towards the mesoderm and cardiac lineages. To this end, transcriptome profiling by microarray was performed on differentiating human pluripotent stem cells sampled at eleven consecutive days. The gene expression data was analyzed using the five-stage analysis framework proposed in this study, including data preparation, exploratory data analysis, confirmatory analysis, biological knowledge discovery, and visualization of the results. Clustering analysis revealed several distinct expression profiles during differentiation. Genes with an early transient response were strongly related to embryonic- and mesendoderm development, for example CER1 and NODAL. Pluripotency genes, such as NANOG and SOX2, exhibited substantial downregulation shortly after onset of differentiation. Rapid induction of genes related to metal ion response, cardiac tissue development, and muscle contraction were observed around day five and six. Several transcription factors were identified as potential regulators of these processes, e.g. POU1F1, TCF4 and TBP for muscle contraction genes. Pathway analysis revealed temporal activity of several signaling pathways, for example the inhibition of WNT signaling on day 2 and its reactivation on day 4. This study provides a comprehensive characterization of biological events and key regulators of the early differentiation of human pluripotent stem cells towards the mesoderm and cardiac lineages. The proposed analysis framework can be used to structure data analysis in future research, both in stem cell differentiation, and more generally, in biomedical big data analytics. PMID:28654683

A data analysis framework for biomedical big data: Application on mesoderm differentiation of human pluripotent stem cells.

PubMed

Ulfenborg, Benjamin; Karlsson, Alexander; Riveiro, Maria; Améen, Caroline; Åkesson, Karolina; Andersson, Christian X; Sartipy, Peter; Synnergren, Jane

2017-01-01

The development of high-throughput biomolecular technologies has resulted in generation of vast omics data at an unprecedented rate. This is transforming biomedical research into a big data discipline, where the main challenges relate to the analysis and interpretation of data into new biological knowledge. The aim of this study was to develop a framework for biomedical big data analytics, and apply it for analyzing transcriptomics time series data from early differentiation of human pluripotent stem cells towards the mesoderm and cardiac lineages. To this end, transcriptome profiling by microarray was performed on differentiating human pluripotent stem cells sampled at eleven consecutive days. The gene expression data was analyzed using the five-stage analysis framework proposed in this study, including data preparation, exploratory data analysis, confirmatory analysis, biological knowledge discovery, and visualization of the results. Clustering analysis revealed several distinct expression profiles during differentiation. Genes with an early transient response were strongly related to embryonic- and mesendoderm development, for example CER1 and NODAL. Pluripotency genes, such as NANOG and SOX2, exhibited substantial downregulation shortly after onset of differentiation. Rapid induction of genes related to metal ion response, cardiac tissue development, and muscle contraction were observed around day five and six. Several transcription factors were identified as potential regulators of these processes, e.g. POU1F1, TCF4 and TBP for muscle contraction genes. Pathway analysis revealed temporal activity of several signaling pathways, for example the inhibition of WNT signaling on day 2 and its reactivation on day 4. This study provides a comprehensive characterization of biological events and key regulators of the early differentiation of human pluripotent stem cells towards the mesoderm and cardiac lineages. The proposed analysis framework can be used to structure data analysis in future research, both in stem cell differentiation, and more generally, in biomedical big data analytics.

Organotypic culture of human amnion cells in air-liquid interface as a potential substitute for skin regeneration.

PubMed

Fatimah, Simat Siti; Chua, Kienhui; Tan, Geok Chin; Azmi, Tengku Ibrahim; Tan, Ay Eeng; Abdul Rahman, Hayati

2013-08-01

The aim of the present study was to evaluate the effects of air-liquid interface on the differentiation potential of human amnion epithelial cells (HAECs) to skin-like substitute in organotypic culture. HAECs at passage 1-2 were seeded onto a fibrin layer populated with human amnion mesenchymal cells to form the organotypic cultures. The organotypic HAECs were then cultured for 7, 14 and 21 d in two types of culture system: the submerged culture and the air-liquid interface culture. Cell morphogenesis was examined under the light and electron microscopes (transmission and scanning) and analyzed by immunohistochemistry. Organotypic HAECs formed a single layer epithelium after 3 wk in submerged as well as air-liquid interface cultures. Ultrastructurally, desmosomes were observed in organotypic HAECs cultured in the air-liquid interface but not in the submerged culture. The presence of desmosomes marked the onset of early epidermal differentiation. Organotypic HAECs were positive against anti-CK18 and anti-CK14 in both the submerged and the air-liquid interface cultures. The co-expression of CK14 and CK18 suggested that differentiation of HAECs into skin may follow the process of embryonic skin development. However, weak expression of CK14 was observed after 2 and 3 wk of culture in air-liquid interface. CK10, involucrin, type IV collagen and laminin-5 expression was absent in organotypic HAECs. This observation reflects the initial process of embryonic epidermal differentiation and stratification. Results from the present study suggest that the air-liquid interface could stimulate early differentiation of organotypic HAECs to epidermal cells, with a potential use for skin regeneration. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Environmental estrogens alter early development in Xenopus laevis.

PubMed

Bevan, Cassandra L; Porter, Donna M; Prasad, Anita; Howard, Marthe J; Henderson, Leslie P

2003-04-01

A growing number of environmental toxicants found in pesticides, herbicides, and industrial solvents are believed to have deleterious effects on development by disrupting hormone-sensitive processes. We exposed Xenopus laevis embryos at early gastrula to the commonly encountered environmental estrogens nonylphenol, octylphenol, and methoxychlor, the antiandrogen, p,p-DDE, or the synthetic androgen, 17 alpha-methyltestosterone at concentrations ranging from 10 nM to 10 microM and examined them at tailbud stages (approximately 48 hr of treatment). Exposure to the three environmental estrogens, as well as to the natural estrogen 17 beta-estradiol, increased mortality, induced morphologic deformations, increased apoptosis, and altered the deposition and differentiation of neural crest-derived melanocytes in tailbud stage embryos. Although neural crest-derived melanocytes were markedly altered in embryos treated with estrogenic toxicants, expression of the early neural crest maker Xslug, a factor that regulates both the induction and subsequent migration of neural crest cells, was not affected, suggesting that the disruption induced by these compounds with respect to melanocyte development may occur at later stages of their differentiation. Co-incubation of embryos with the pure antiestrogen ICI 182,780 blocked the ability of nonylphenol to induce abnormalities in body shape and in melanocyte differentiation but did not block the effects of methoxychlor. Our data indicate not only that acute exposure to these environmental estrogens induces deleterious effects on early vertebrate development but also that different environmental estrogens may alter the fate of a specific cell type via different mechanisms. Finally, our data suggest that the differentiation of neural crest-derived melanocytes may be particularly sensitive to the disruptive actions of these ubiquitous chemical contaminants.

Population genomics of early events in the ecological differentiation of bacteria

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

Shapiro, Jesse B.; Friedman, Jonatan; Cordero, Otto X.

Genetic exchange is common among bacteria, but its effect on population diversity during ecological differentiation remains controversial. A fundamental question is whether advantageous mutations lead to selection of clonal genomes or, as in sexual eukaryotes, sweep through populations on their own. Here, we show that in two recently diverged populations of ocean bacteria, ecological differentiation has occurred akin to a sexual mechanism: A few genome regions have swept through subpopulations in a habitat-specific manner, accompanied by gradual separation of gene pools as evidenced by increased habitat specificity of the most recent recombinations. These findings reconcile previous, seemingly contradictory empirical observationsmore » of the genetic structure of bacterial populations and point to a more unified process of differentiation in bacteria and sexual eukaryotes than previously thought.« less

Molecular Memory of Morphologies by Septins during Neuron Generation Allows Early Polarity Inheritance.

PubMed

Boubakar, Leila; Falk, Julien; Ducuing, Hugo; Thoinet, Karine; Reynaud, Florie; Derrington, Edmund; Castellani, Valérie

2017-08-16

Transmission of polarity established early during cell lineage history is emerging as a key process guiding cell differentiation. Highly polarized neurons provide a fascinating model to study inheritance of polarity over cell generations and across morphological transitions. Neural crest cells (NCCs) migrate to the dorsal root ganglia to generate neurons directly or after cell divisions in situ. Using live imaging of vertebrate embryo slices, we found that bipolar NCC progenitors lose their polarity, retracting their processes to round for division, but generate neurons with bipolar morphology by emitting processes from the same locations as the progenitor. Monitoring the dynamics of Septins, which play key roles in yeast polarity, indicates that Septin 7 tags process sites for re-initiation of process growth following mitosis. Interfering with Septins blocks this mechanism. Thus, Septins store polarity features during mitotic rounding so that daughters can reconstitute the initial progenitor polarity. Copyright © 2017 Elsevier Inc. All rights reserved.

Gestalt perception modulates early visual processing.

PubMed

Herrmann, C S; Bosch, V

2001-04-17

We examined whether early visual processing reflects perceptual properties of a stimulus in addition to physical features. We recorded event-related potentials (ERPs) of 13 subjects in a visual classification task. We used four different stimuli which were all composed of four identical elements. One of the stimuli constituted an illusory Kanizsa square, another was composed of the same number of collinear line segments but the elements did not form a Gestalt. In addition, a target and a control stimulus were used which were arranged differently. These stimuli allow us to differentiate the processing of colinear line elements (stimulus features) and illusory figures (perceptual properties). The visual N170 in response to the illusory figure was significantly larger as compared to the other collinear stimulus. This is taken to indicate that the visual N170 reflects cognitive processes of Gestalt perception in addition to attentional processes and physical stimulus properties.

Autophagy in Human Embryonic Stem Cells

PubMed Central

Tra, Thien; Gong, Lan; Kao, Lin-Pin; Li, Xue-Lei; Grandela, Catarina; Devenish, Rodney J.; Wolvetang, Ernst; Prescott, Mark

2011-01-01

Autophagy (macroautophagy) is a degradative process that involves the sequestration of cytosolic material including organelles into double membrane vesicles termed autophagosomes for delivery to the lysosome. Autophagy is essential for preimplantation development of mouse embryos and cavitation of embryoid bodies. The precise roles of autophagy during early human embryonic development, remain however largely uncharacterized. Since human embryonic stem cells constitute a unique model system to study early human embryogenesis we investigated the occurrence of autophagy in human embryonic stem cells. We have, using lentiviral transduction, established multiple human embryonic stem cell lines that stably express GFP-LC3, a fluorescent marker for the autophagosome. Each cell line displays both a normal karyotype and pluripotency as indicated by the presence of cell types representative of the three germlayers in derived teratomas. GFP expression and labelling of autophagosomes is retained after differentiation. Baseline levels of autophagy detected in cultured undifferentiated hESC were increased or decreased in the presence of rapamycin and wortmannin, respectively. Interestingly, autophagy was upregulated in hESCs induced to undergo differentiation by treatment with type I TGF-beta receptor inhibitor SB431542 or removal of MEF secreted maintenance factors. In conclusion we have established hESCs capable of reporting macroautophagy and identify a novel link between autophagy and early differentiation events in hESC. PMID:22110659

Effects of Earth's rotation on the early differentiation of a terrestrial magma ocean

NASA Astrophysics Data System (ADS)

Maas, Christian; Hansen, Ulrich

2015-11-01

Similar to other terrestrial planets like Moon and Mars, Earth experienced a magma ocean period about 4.5 billion years ago. On Earth differentiation processes in the magma ocean set the initial conditions for core formation and mantle evolution. During the magma ocean period Earth was rotating significantly faster than today. Further, the viscosity of the magma was low, thus that planetary rotation potentially played an important role for differentiation. However, nearly all previous studies neglect rotational effects. All in all, our results suggest that planetary rotation plays an important role for magma ocean crystallization. We employ a 3-D numerical model to study crystal settling in a rotating and vigorously convecting early magma ocean. We show that crystal settling in a terrestrial magma ocean is crucially affected by latitude as well as by rotational strength and crystal density. Due to rotation an inhomogeneous accumulation of crystals during magma ocean solidification with a distinct crystal settling between pole and equator could occur. One could speculate that this may have potentially strong effects on the magma ocean solidification time and the early mantle composition. It could support the development of a basal magma ocean and the formation of anomalies at the core-mantle boundary in the equatorial region, reaching back to the time of magma ocean solidification.

SPORADIC GOITROUS CRETINISM

PubMed Central

Mosier, H. David

1959-01-01

Five to 10 per cent of cretinism in the United States is due to some congenital enzymatic defect in thyroid hormone synthesis. The clinical signs of hypothyroidism appear in early infancy. Differentiation from athyreotic cretinism is important because the metabolic defect tends to be familial and its presence in the patient's infant relatives should be diagnosed as early as possible. The differentiation is easily made if a goiter is discernible, but if it is not, radioiodine uptake should be measured, for in this condition the uptake is normal or greater. Thyroid replacement is the treatment in either the athyreotic state or the metabolic deficiency. The three known defects in thyroid hormone synthesis are (1) failure to oxidize iodine to elemental iodine resulting in failure of all subsequent processes; (2) failure to deiodinate free iodotyrosine, and (3) failure to form iodothyronine although the previous steps are accomplished. PMID:13618742

Dynamic Organization of lncRNA and Circular RNA Regulators Collectively Controlled Cardiac Differentiation in Humans.

PubMed

Li, Yongsheng; Zhang, Jinwen; Huo, Caiqin; Ding, Na; Li, Junyi; Xiao, Jun; Lin, Xiaoyu; Cai, Benzhi; Zhang, Yunpeng; Xu, Juan

2017-10-01

Advances in developmental cardiology have increased our understanding of the early aspects of heart differentiation. However, understanding noncoding RNA (ncRNA) transcription and regulation during this process remains elusive. Here, we constructed transcriptomes for both long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in four important developmental stages ranging from early embryonic to cardiomyocyte based on high-throughput sequencing datasets, which indicate the high stage-specific expression patterns of two ncRNA types. Additionally, higher similarities of samples within each stage were found, highlighting the divergence of samples collected from distinct cardiac developmental stages. Next, we developed a method to identify numerous lncRNA and circRNA regulators whose expression was significantly stage-specific and shifted gradually and continuously during heart differentiation. We inferred that these ncRNAs are important for the stages of cardiac differentiation. Moreover, transcriptional regulation analysis revealed that the expression of stage-specific lncRNAs is controlled by known key stage-specific transcription factors (TFs). In addition, circRNAs exhibited dynamic expression patterns independent from their host genes. Functional enrichment analysis revealed that lncRNAs and circRNAs play critical roles in pathways that are activated specifically during heart differentiation. We further identified candidate TF-ncRNA-gene network modules for each differentiation stage, suggesting the dynamic organization of lncRNAs and circRNAs collectively controlled cardiac differentiation, which may cause heart-related diseases when defective. Our study provides a foundation for understanding the dynamic regulation of ncRNA transcriptomes during heart differentiation and identifies the dynamic organization of novel key lncRNAs and circRNAs to collectively control cardiac differentiation. Copyright © 2017. Published by Elsevier B.V.

Time Course of Attentional Bias in Anxiety: Emotion and Gender Specificity

PubMed Central

Sass, Sarah M.; Heller, Wendy; Stewart, Jennifer L.; Silton, Rebecca Levin; Edgar, J. Christopher; Fisher, Joscelyn E.; Miller, Gregory A.

2011-01-01

Anxiety is characterized by cognitive biases, including attentional bias to emotional (especially threatening) stimuli. Accounts differ on the time course of attention to threat, but the literature generally confounds emotional valence and arousal and overlooks gender effects, both addressed in the present study. Nonpatients high in self-reported anxious apprehension, anxious arousal, or neither completed an emotion-word Stroop task during ERP recording. Hypotheses differentiated time course of preferential attention to emotional stimuli. Individuals high in anxious apprehension and anxious arousal showed distinct early ERP evidence of preferential processing of emotionally arousing stimuli along with some evidence for gender differences in processing. Healthy controls showed gender differences at both early and later processing stages. The conjunction of valence, arousal, and gender is critical in the time course of attentional bias. PMID:19863758

The Multiple Subfunctions of Attention: Differential Developmental Gateways to Literacy and Numeracy

ERIC Educational Resources Information Center

Steele, Ann; Karmiloff-Smith, Annette; Cornish, Kim; Scerif, Gaia

2012-01-01

Attention is construed as multicomponential, but the roles of its distinct subfunctions in shaping the broader developing cognitive landscape are poorly understood. The current study assessed 3- to 6-year-olds (N = 83) to: (a) trace developmental trajectories of attentional processes and their structure in early childhood and (b) measure the…

Up Front, in Hope: The Value of Early Intervention for Children with Fetal Alcohol Syndrome.

ERIC Educational Resources Information Center

Harwood, Maureen; Kleinfeld, Judith Smilg

2002-01-01

Differentiates fetal alcohol syndrome (FAS) from fetal alcohol effects (FAE) and discusses difficulties in diagnosing these conditions. Describes the effects of FAS/FAE on young children, detailing impact on sensory processing, focusing attention, and cognitive development in infants, toddlers, and preschoolers. Presents suggestions for caregivers…

Differentiating Developmental Trajectories for Conduct, Emotion, and Peer Problems Following Early Deprivation

ERIC Educational Resources Information Center

Sonuga-Barke, Edmund J.; Schlotz, Wolff; Kreppner, Jana

2010-01-01

The development of conduct and emotional problems involves a complex interplay between environmental and genetic factors. The child-rearing environment contributes to this process. Gross deviations, such as those seen in abusive or neglectful homes, or where the parent has serious mental health problems, have been shown to contribute to the…

The Talent Development of a Musically Gifted Adolescent in Singapore

ERIC Educational Resources Information Center

Ho, Pauline S. K.; Chong, Sylvia N. Y.

2010-01-01

Using Gagne's Differentiated Model of Giftedness and Talent (DMGT) as a conceptual model, this study investigated the factors that influenced the talent development process of a musically gifted adolescent in Singapore. Five macro themes emerged as key catalysts that impacted the adolescent's talent growth: (1) natural abilities; (2) early musical…

Dermatoglyphics--a possible biomarker in the neurodevelopmental model for the origin of mental disorders.

PubMed

Ahmed-Popova, Ferihan M; Mantarkov, Mladen J; Sivkov, Stefan T; Akabaliev, Valentin H

2014-01-01

Dermatoglyphic pattern formation and differentiation are complex processes which have been in the focus of research interest ever since dermatoglyphics became a science. The patterns' early differentiation and genetic uniqueness as well as the relatively simple methods used to obtain and store fingerprints make it possible to study the relationship between certain dermatoglyphic characteristics and the underlying pathological processes in a number of diseases, including mental disorders. The present review reports published data from fundamental and clinical studies on dermatoglyphics primarily in schizophrenia and bipolar disorder to lend additional support for the neurodevelopmental hypothesis in the etiology of these disorders. Following an analysis of the theories of dermatoglyphics formation and the complex association between ridge patterns and central nervous system in early embryogenesis, an attempt is made to present dermatoglyphics as possible biological markers of impaired neurodevelopment. The contradictory data in the literature on dermatoglyphics in mental disorders suggest the need for further studies on these biological markers in order to identify their place in the neurodevelopmental etiological model of these diseases.

A review of recent studies on differential reinforcement during skill acquisition in early intervention.

PubMed

Vladescu, Jason C; Kodak, Tiffany

2010-01-01

Although the use of differential reinforcement has been recommended in previous investigations and in early intervention curriculum manuals, few studies have evaluated the best method for providing differential reinforcement to maximize independent responding. This paper reviews previous research on the effectiveness of differential reinforcement as treatment and describes important areas of future research.

Assessment of nutrient remobilization through structural changes of palisade and spongy parenchyma in oilseed rape leaves during senescence.

PubMed

Sorin, Clément; Musse, Maja; Mariette, François; Bouchereau, Alain; Leport, Laurent

2015-02-01

Differential palisade and spongy parenchyma structural changes in oilseed rape leaf were demonstrated. These dismantling processes were linked to early senescence events and associated to remobilization processes. During leaf senescence, an ordered cell dismantling process allows efficient nutrient remobilization. However, in Brassica napus plants, an important amount of nitrogen (N) in fallen leaves is associated with low N remobilization efficiency (NRE). The leaf is a complex organ mainly constituted of palisade and spongy parenchyma characterized by different structures and functions concerning water relations and carbon fixation. The aim of the present study was to demonstrate a specific structural evolution of these parenchyma throughout natural senescence in B. napus, probably linked to differential nutrient remobilization processes. The study was performed on 340 leaves from 32 plants during an 8-week development period under controlled growing conditions. Water distribution and status at the cellular level were investigated by low-field proton nuclear magnetic resonance (NMR), while light and electron microscopy were used to observe cell and plast structure. Physiological parameters were determined on all leaves studied and used as indicators of leaf development and remobilization progress. The results revealed a process of hydration and cell enlargement of leaf tissues associated with senescence. Wide variations were observed in the palisade parenchyma while spongy cells changed only very slightly. The major new functional information revealed was the link between the early senescence events and specific tissue dismantling processes.

[Molecular cloning, expression of rat Msx-1 and Msx-2 during early embryo genesis and roles for mandibular chondrogenesis].

PubMed

Ishiguro, S

1999-03-01

Quail-chick chimera experiments have shown a contribution of carnial neural crest cells to the craniofacial skeletal elements. Moreover, tissue interactions between epithelial-mesenchymal interaction during early facial process development are required for both skeletal differentiation and morphogenesis. In this study, it was observed that Msx homeobox containing genes expressed in the facial process were important molecules of cartilage morphogenesis. Rat cDNAs were isolated and encoded by Msx-1 and -2, and then the expression patterns using in situ hybridization were investigated during early rat face development. These genes were correlatively expressed in the cranial neural crest forming area (E 9.5 dpc) and the facial process (E 12.5 dpc). Antisence inhibition of Msx genes in the E 12.5 mandibular process exhibited the alteration of their gene expression and cartilage patterns. Antisence inhibition of Msx-1 induced lack of the medial portion of cartilage, and antisence inhibition of Msx-2 enhanced chondrogenesis of mandibular process under the organ culture condition. Thus it was concluded that expression of Msx genes during mandibular process development comprises important signals of chondrogenesis.

Effects of rotation on crystal settling in a terrestrial magma ocean: Spherical shell model

NASA Astrophysics Data System (ADS)

Maas, C.; Hansen, U.

2015-12-01

Like Moon or Mars, Earth experienced one or several deep magma ocean periods of globalextent in a later stage of its accretion. The crystallization of these magma oceans is of keyimportance for the chemical structure of Earth, the mantle evolution and the onset of platetectonics. Due to the fast rotation of early Earth and the small magma viscosity, rotationprobably had a profound effect on differentiation processes. For example, Matyska et al.[1994] propose that the distribution of heterogeneities like the two large low shear velocityprovinces (LLSVP) at the core mantle boundary is influenced by rotational dynamicsof early Earth. Further Garnero and McNamara [2008] suggest that the LLSVPs arevery long-living anomalies, probably reaching back to the time of differentiation andsolidification of Earth. However, nearly all previous studies neglect the effects of rotation.In our previous work using a Cartesian model, a strong influence of rotation as well asof latitude on the differentiation processes in an early magma ocean was revealed. Weshowed that crystal settling in an early stage of magma ocean crystallization cruciallydepends on latitude as well as on rotational strength and crystal density.In order to overcome the restrictions as to the geometry of the Cartesian model, we arecurrently developing a spherical model to simulate crystal settling in a rotating sphericalshell. This model will allow us not only to investigate crystal settling at the poles andthe equator, but also at latitudes in-between these regions, as well as the migration ofcrystals between poles and equator. ReferencesE. J. Garnero and A. K. McNamara. Structure and dynamics of earth's lower mantle.Science, 320(5876):626-628, 2008.C. Matyska, J. Moser, and D. A. Yuen. The potential influence of radiative heat transferon the formation of megaplumes in the lower mantle. Earth and Planetary ScienceLetters, 125(1):255-266, 1994.

Analysis of preplate splitting and early cortical development illuminates the biology of neurological disease.

PubMed

Olson, Eric C

2014-01-01

The development of the layered cerebral cortex starts with a process called preplate splitting. Preplate splitting involves the establishment of prospective cortical layer 6 (L6) neurons within a plexus of pioneer neurons called the preplate. The forming layer 6 splits the preplate into a superficial layer of pioneer neurons called the marginal zone and a deeper layer of pioneer neurons called the subplate. Disruptions of this early developmental event by toxin exposure or mutation are associated with neurological disease including severe intellectual disability. This review explores recent findings that reveal the dynamism of gene expression and morphological differentiation during this early developmental period. Over 1000 genes show expression increases of ≥2-fold during this period in differentiating mouse L6 neurons. Surprisingly, 88% of previously identified non-syndromic intellectual-disability (NS-ID) genes are expressed at this time and show an average expression increase of 1.6-fold in these differentiating L6 neurons. This changing genetic program must, in part, support the dramatic cellular reorganizations that occur during preplate splitting. While different models have been proposed for the formation of a layer of L6 cortical neurons within the preplate, original histological studies and more recent work exploiting transgenic mice suggest that the process is largely driven by the coordinated polarization and coalescence of L6 neurons rather than by cellular translocation or migration. The observation that genes associated with forms of NS-ID are expressed during very early cortical development raises the possibility of studying the relevant biological events at a time point when the cortex is small, contains relatively few cell types, and few functional circuits. This review then outlines how explant models may prove particularly useful in studying the consequence of toxin and mutation on the etiology of some forms of NS-ID.

MicroRNA-127 Promotes Mesendoderm Differentiation of Mouse Embryonic Stem Cells by Targeting Left-Right Determination Factor 2.

PubMed

Ma, Haixia; Lin, Yu; Zhao, Zhen-Ao; Lu, Xukun; Yu, Yang; Zhang, Xiaoxin; Wang, Qiang; Li, Lei

2016-06-03

Specification of the three germ layers is a fundamental process and is essential for the establishment of organ rudiments. Multiple genetic and epigenetic factors regulate this dynamic process; however, the function of specific microRNAs in germ layer differentiation remains unknown. In this study, we established that microRNA-127 (miR-127) is related to germ layer specification via microRNA array analysis of isolated three germ layers of E7.5 mouse embryos and was verified through differentiation of mouse embryonic stem cells. miR-127 is highly expressed in endoderm and primitive streak. Overexpression of miR-127 increases and inhibition of miR-127 decreases the expression of mesendoderm markers. We further show that miR-127 promotes mesendoderm differentiation through the nodal pathway, a determinative signaling pathway in early embryogenesis. Using luciferase reporter assay, left-right determination factor 2 (Lefty2), an antagonist of nodal, is identified to be a novel target of miR-127. Furthermore, the role of miR-127 in mesendoderm differentiation is attenuated by Lefty2 overexpression. Altogether, our results indicate that miR-127 accelerates mesendoderm differentiation of mouse embryonic stem cells through nodal signaling by targeting Lefty2. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Coupled 182W-142Nd constraint for early Earth differentiation

PubMed Central

Moynier, Frederic; Yin, Qing-Zhu; Irisawa, Keita; Boyet, Maud; Jacobsen, Benjamin; Rosing, Minik T.

2010-01-01

Recent high precision 142Nd isotope measurements showed that global silicate differentiation may have occurred as early as 30–75 Myr after the Solar System formation [Bennett V, et al. (2007) Science 318:1907–1910]. This time scale is almost contemporaneous with Earth’s core formation at ∼30 Myr [Yin Q, et al. (2002) Nature 418:949–952]. The 182Hf-182W system provides a powerful complement to the 142Nd results for early silicate differentiation, because both core formation and silicate differentiation fractionate Hf from W. Here we show that eleven terrestrial samples from diverse tectonic settings, including five early Archean samples from Isua, Greenland, of which three have been previously shown with 142Nd anomalies, all have a homogeneous W isotopic composition, which is ∼2ε-unit more radiogenic than the chondritic value. By using a 3-stage model calculation that describes the isotopic evolution in chondritic reservoir and core segregation, as well as silicate differentiation, we show that the W isotopic composition of terrestrial samples provides the most stringent time constraint for early core formation (27.5–38 Myr) followed by early terrestrial silicate differentiation (38–75 Myr) that is consistent with the terrestrial 142Nd anomalies. PMID:20534492

Antiadipogenic effects of subthermal electric stimulation at 448 kHz on differentiating human mesenchymal stem cells.

PubMed

Hernández-Bule, María Luisa; Martínez-Botas, Javier; Trillo, María Ángeles; Paíno, Carlos L; Úbeda, Alejandro

2016-05-01

The 448 kHz capacitive‑resistive electric transfer (CRET) is an electrothermal therapy currently applied in anticellulite and antiobesity treatments. The aim of the present study was to determine whether exposure to the CRET electric signal at subthermal doses affected early adipogenic processes in adipose‑derived stem cells (ADSC) from human donors. ADSC were incubated for 2 or 9 days in the presence of adipogenic medium, and exposed or sham‑exposed to 5 min pulses of 448 kHz electric signal at 50 µA/mm2 during the last 48 h of the incubation. Colorimetric, immunofluorescence, western blotting and reverse transcription‑quantitative polymerase chain reaction assays were performed to assess adipogenic differentiation of the ADSC. Electric stimulation significantly decreased cytoplasmic lipid content, after both 2 and 9 days of differentiation. The antiadipogenic response in the 9 day samples was accompanied by activation of mitogen‑activated protein kinase kinase 1/2, decreased expression and partial inactivation of peroxisome proliferator‑activated receptor (PPAR) γ, which was translocated from the nucleus to the cytoplasm, together with a significant decrease in the expression levels of the PPARG1 gene, perilipin, angiopoietin‑like protein 4 and fatty acid synthase. These results demonstrated that subthermal stimulation with CRET interferes with the early adipogenic differentiation in ADSC, indicating that the electric stimulus itself can modulate processes controlling the synthesis and mobilization of fat, even in the absence of the concomitant thermal and mechanical components of the thermoelectric therapy CRET.

Electrophysiological evidence for effects of color knowledge in object recognition.

PubMed

Lu, Aitao; Xu, Guiping; Jin, Hua; Mo, Lei; Zhang, Jijia; Zhang, John X

2010-01-29

Knowledge about the typical colors associated with familiar everyday objects (i.e., strawberries are red) is well-known to be represented in the conceptual semantic system. Evidence that such knowledge may also play a role in early perceptual processes for object recognition is scant. In the present ERP study, participants viewed a list of object pictures and detected infrequent stimulus repetitions. Results show that shortly after stimulus onset, ERP components indexing early perceptual processes, including N1, P2, and N2, differentiated between objects in their appropriate or congruent color from these objects in an inappropriate or incongruent color. Such congruence effect also occurred in N3 associated with semantic processing of pictures but not in N4 for domain-general semantic processing. Our results demonstrate a clear effect of color knowledge in early object recognition stages and support the following proposal-color as a surface property is stored in a multiple-memory system where pre-semantic perceptual and semantic conceptual representations interact during object recognition. (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Separating myoblast differentiation from muscle cell fusion using IGF-I and the p38 MAP kinase inhibitor SB202190.

PubMed

Gardner, Samantha; Gross, Sean M; David, Larry L; Klimek, John E; Rotwein, Peter

2015-10-01

The p38 MAP kinases play critical roles in skeletal muscle biology, but the specific processes regulated by these kinases remain poorly defined. Here we find that activity of p38α/β is important not only in early phases of myoblast differentiation, but also in later stages of myocyte fusion and myofibrillogenesis. By treatment of C2 myoblasts with the promyogenic growth factor insulin-like growth factor (IGF)-I, the early block in differentiation imposed by the p38 chemical inhibitor SB202190 could be overcome. Yet, under these conditions, IGF-I could not prevent the later impairment of muscle cell fusion, as marked by the nearly complete absence of multinucleated myofibers. Removal of SB202190 from the medium of differentiating myoblasts reversed the fusion block, as multinucleated myofibers were detected several hours later and reached ∼90% of the culture within 30 h. Analysis by quantitative mass spectroscopy of proteins that changed in abundance following removal of the inhibitor revealed a cohort of upregulated muscle-enriched molecules that may be important for both myofibrillogenesis and fusion. We have thus developed a model system that allows separation of myoblast differentiation from muscle cell fusion and should be useful in identifying specific steps regulated by p38 MAP kinase-mediated signaling in myogenesis. Copyright © 2015 the American Physiological Society.

Gene expression profiling reveals different molecular patterns in G-protein coupled receptor signaling pathways between early- and late-onset preeclampsia.

PubMed

Liang, Mengmeng; Niu, Jianmin; Zhang, Liang; Deng, Hua; Ma, Jian; Zhou, Weiping; Duan, Dongmei; Zhou, Yuheng; Xu, Huikun; Chen, Longding

2016-04-01

Early-onset preeclampsia and late-onset preeclampsia have been regarded as two different phenotypes with heterogeneous manifestations; To gain insights into the pathogenesis of the two traits, we analyzed the gene expression profiles in preeclamptic placentas. A whole genome-wide microarray was used to determine the gene expression profiles in placental tissues from patients with early-onset (n = 7; <34 weeks), and late-onset (n = 8; >36 weeks) preeclampsia and their controls who delivered preterm (n = 5; <34 weeks) or at term (n = 5; >36 weeks). Genes were termed differentially expressed if they showed a fold-change ≥ 2 and q-value < 0.05. Quantitative real-time reverse transcriptase PCR was used to verify the results. Western blotting was performed to verify the expressions of secreted genes at the protein level. Six hundred twenty-seven genes were differentially expressed in early-compared with late-onset preeclampsia (177 genes were up-regulated and 450 were down-regulated). Gene ontology analysis identified significant alterations in several biological processes; the top two were immune response and cell surface receptor linked signal transduction. Among the cell surface receptor linked signal transduction-related, differentially expressed genes, those involved in the G-protein coupled receptor protein signaling pathway were significantly enriched. G-protein coupled receptor signaling pathway related genes, such as GPR124 and MRGPRF, were both found to be down-regulated in early-onset preeclampsia. The results were consistent with those of western blotting that the abundance of GPR124 was lower in early-onset compared with late-onset preeclampsia. The different gene expression profiles reflect the different levels of transcription regulation between the two conditions and supported the hypothesis that they are separate disease entities. Moreover, the G-protein coupled receptor signaling pathway related genes may contribute to the mechanism underlying early- and late-onset preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Regulation of neuroblastoma differentiation by forkhead transcription factors FOXO1/3/4 through the receptor tyrosine kinase PDGFRA

PubMed Central

Mei, Yang; Wang, Zhanxiang; Zhang, Lei; Zhang, Yiru; Li, Xiaoyu; Liu, Huihui; Ye, Jing; You, Han

2012-01-01

Neuroblastoma is a common childhood malignant tumor originated from the neural crest-derived sympathetic nervous system. A crucial early event in neuroblastoma pathogenesis is arrested differentiation of neuroblasts at various stages. Treatment of neuroblastoma with TPA and PDGF-BB leads to terminal differentiation of neuroblastoma cells. However, the signaling pathways that are involved in this process remain largely unknown. Here, we report that inhibition of endogenous FOXO proteins attenuated TPA/PDGF-BB mediated differentiation of neuroblastoma cells. Activated FOXO transcription factors acted on PDGFRA promoter to direct its basal mRNA expression as well as its induction upon serum deprivation. Depletion of endogenous PDGFRA in neuroblastoma cells significantly diminished neurite formation and extension under TPA/PDGF-BB treatment. Furthermore, ectopic expression of PDGFRA abolished the blockage of neuroblastoma differentiation by FOXOs inhibition. These findings define the FOXO–PDGFRA axis as crucial mechanistic components that govern TPA-induced neuroblastoma differentiation. PMID:22411791

AKT1 provides an essential survival signal required for differentiation and stratification of primary human keratinocytes.

PubMed

Thrash, Barry R; Menges, Craig W; Pierce, Robert H; McCance, Dennis J

2006-04-28

Keratinocyte differentiation and stratification are complex processes involving multiple signaling pathways, which convert a basal proliferative cell into an inviable rigid squame. Loss of attachment to the basement membrane triggers keratinocyte differentiation, while in other epithelial cells, detachment from the extracellular matrix leads to rapid programmed cell death or anoikis. The potential role of AKT in providing a survival signal necessary for stratification and differentiation of primary human keratinocytes was investigated. AKT activity increased during keratinocyte differentiation and was attributed to the specific activation of AKT1 and AKT2. Targeted reduction of AKT1 expression, but not AKT2, by RNA interference resulted in an abnormal epidermis in organotypic skin cultures with a thin parabasal region and a pronounced but disorganized cornified layer. This abnormal stratification was due to significant cell death in the suprabasal layers and was alleviated by caspase inhibition. Normal expression patterns of both early and late markers of keratinocyte differentiation were also disrupted, producing a poorly developed stratum corneum.

The influence of gravity on the process of development of animal systems

NASA Technical Reports Server (NTRS)

Malacinski, G. M.; Neff, A. W.

1984-01-01

The development of animal systems is described in terms of a series of overlapping phases: pattern specification; differentiation; growth; and aging. The extent to which altered (micro) gravity (g) affects those phases is briefly reviewed for several animal systems. As a model, amphibian egg/early embryo is described. Recent data derived from clinostat protocols indicates that microgravity simulation alters early pattern specification (dorsal/ventral polarity) but does not adversely influence subsequent morphogenesis. Possible explanations for the absence of catastrophic microgravity effects on amphibian embryogenesis are discussed.

Synchronisms between bud and cambium phenology in black spruce: early-flushing provenances exhibit early xylem formation.

PubMed

Perrin, Magali; Rossi, Sergio; Isabel, Nathalie

2017-05-01

Bud and cambial phenology represent the adaptation of species to the local environment that allows the growing season to be maximized while minimizing the risk of frost for the developing tissues. The temporal relationship between the apical and radial meristems can help in the understanding of tree growth as a whole process. The aim of this study was to compare cambial phenology in black spruce (Picea mariana (Mill.) B.S.P.) provenances classified as early and late bud flushing. The different phases of cambial phenology were assessed on wood microcores sampled weekly from April to October in 2014 and 2015 from 61 trees growing in a provenance trial in Quebec, Canada. Trees showing an early bud flush also exhibited early reactivation of xylem differentiation, although an average difference of 12 days for buds corresponded to small although significant differences of 4 days for xylem. Provenances with early bud flush had an early bud set and completed xylem formation earlier than late bud flush provenances. No significant difference in the period of xylem formation and total growth was observed between the flushing classes. Our results demonstrate that the ecotype differentiation of black spruce provenances represented by the phenological adaptation of buds to the local climate corresponds to specific growth dynamics of the xylem. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A REVIEW OF RECENT STUDIES ON DIFFERENTIAL REINFORCEMENT DURING SKILL ACQUISITION IN EARLY INTERVENTION

PubMed Central

Vladescu, Jason C; Kodak, Tiffany

2010-01-01

Although the use of differential reinforcement has been recommended in previous investigations and in early intervention curriculum manuals, few studies have evaluated the best method for providing differential reinforcement to maximize independent responding. This paper reviews previous research on the effectiveness of differential reinforcement as treatment and describes important areas of future research. PMID:21119913

Heparan sulfates and the decrease of N-glycans promote early adipogenic differentiation rather than myogenesis of murine myogenic progenitor cells.

PubMed

Grassot, Vincent; Bouchatal, Amel; Da Silva, Anne; Chantepie, Sandrine; Papy-Garcia, Dulce; Maftah, Abderrahman; Gallet, Paul-François; Petit, Jean-Michel

In vitro, extracted muscle satellite cells, called myogenic progenitor cells, can differentiate either in myotubes or preadipocytes, depending on environmental factors and the medium. Transcriptomic analyses on glycosylation genes during satellite cells differentiation into myotubes showed that 31 genes present a significant variation of expression at the early stages of murine myogenic progenitor cells (MPC) differentiation. In the present study, we analyzed the expression of 383 glycosylation related genes during murine MPC differentiation into preadipocytes and compared the data to those previously obtained during their differentiation into myotubes. Fifty-six glycosylation related genes are specifically modified in their expression during early adipogenesis. The variations correspond mainly to: a decrease of N-glycans, and of alpha (2,3) and (2,6) linked sialic acids, and to a high level of heparan sulfates. A high amount of TGF-β1 in extracellular media during early adipogenesis was also observed. It seems that the increases of heparan sulfates and TGF-β1 favor pre-adipogenic differentition of MPC and possibly prevent their myogenic differentiation. Copyright © 2016 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Did 26Al and impact-induced heating differentiate Mercury?

NASA Astrophysics Data System (ADS)

Bhatia, G. K.; Sahijpal, S.

2017-02-01

Numerical models dealing with the planetary scale differentiation of Mercury are presented with the short-lived nuclide, 26Al, as the major heat source along with the impact-induced heating during the accretion of planets. These two heat sources are considered to have caused differentiation of Mars, a planet with size comparable to Mercury. The chronological records and the thermal modeling of Mars indicate an early differentiation during the initial 1 million years (Ma) of the formation of the solar system. We theorize that in case Mercury also accreted over an identical time scale, the two heat sources could have differentiated the planets. Although unlike Mars there is no chronological record of Mercury's differentiation, the proposed mechanism is worth investigation. We demonstrate distinct viable scenarios for a wide range of planetary compositions that could have produced the internal structure of Mercury as deduced by the MESSENGER mission, with a metallic iron (Fe-Ni-FeS) core of radius 2000 km and a silicate mantle thickness of 400 km. The initial compositions were derived from the enstatite and CB (Bencubbin) chondrites that were formed in the reducing environments of the early solar system. We have also considered distinct planetary accretion scenarios to understand their influence on thermal processing. The majority of our models would require impact-induced mantle stripping of Mercury by hit and run mechanism with a protoplanet subsequent to its differentiation in order to produce the right size of mantle. However, this can be avoided if we increase the Fe-Ni-FeS contents to 71% by weight. Finally, the models presented here can be used to understand the differentiation of Mercury-like exoplanets and the planetary embryos of Venus and Earth.

Embryonic essential myosin light chain regulates fetal lung development in rats.

PubMed

Santos, Marta; Moura, Rute S; Gonzaga, Sílvia; Nogueira-Silva, Cristina; Ohlmeier, Steffen; Correia-Pinto, Jorge

2007-09-01

Congenital diaphragmatic hernia (CDH) is currently the most life-threatening congenital anomaly the major finding of which is lung hypoplasia. Lung hypoplasia pathophysiology involves early developmental molecular insult in branching morphogenesis and a late mechanical insult by abdominal herniation in maturation and differentiation processes. Since early determinants of lung hypoplasia might appear as promising targets for prenatal therapy, proteomics analysis of normal and nitrofen-induced hypoplastic lungs was performed at 17.5 days after conception. The major differentially expressed protein was identified by mass spectrometry as myosin light chain 1a (MLC1a). Embryonic essential MLC1a and regulatory myosin light chain 2 (MLC2) were characterized throughout normal and abnormal lung development by immunohistochemistry and Western blot. Disruption of MLC1a expression was assessed in normal lung explant cultures by antisense oligodeoxynucleotides. Since early stages of normal lung development, MLC1a was expressed in vascular smooth muscle (VSM) cells of pulmonary artery, and MLC2 was present in parabronchial smooth muscle and VSM cells of pulmonary vessels. In addition, early smooth muscle differentiation delay was observed by immunohistochemistry of alpha-smooth muscle actin and transforming growth factor-beta1. Disruption of MLC1a expression during normal pulmonary development led to significant growth and branching impairment, suggesting a role in branching morphogenesis. Both MLC1a and MLC2 were absent from hypoplastic fetal lungs during pseudoglandular stage of lung development, whereas their expression partially recovered by prenatal treatment with vitamin A. Thus, a deficiency in contractile proteins MLC1a and MLC2 might have a role among the early molecular determinants of lung hypoplasia in the rat model of nitrofen-induced CDH.

Petrology and Physics of Magma Ocean Crystallization

NASA Technical Reports Server (NTRS)

Elkins-Tanton, Linda T.; Parmentier, E. M.; Hess, P. C.

2003-01-01

Early Mars is thought to have been melted significantly by the conversion of kinetic energy to heat during accretion of planetesimals. The processes of solidification of a magma ocean determine initial planetary compositional differentiation and the stability of the resulting mantle density profile. The stability and compositional heterogeneity of the mantle have significance for magmatic source regions, convective instability, and magnetic field generation. Significant progress on the dynamical problem of magma ocean crystallization has been made by a number of workers. The work done under the 2003 MFRP grant further explored the implications of early physical processes on compositional heterogeneity in Mars. Our goals were to connect early physical processes in Mars evolution with the present planet's most ancient observable characteristics, including the early, strong magnetic field, the crustal dichotomy, and the compositional characteristics of the SNC meteorite's source regions as well as their formation as isotopically distinct compositions early in Mars's evolution. We had already established a possible relationship between the major element compositions of SNC meteorite sources and processes of Martian magma ocean crystallization and overturn, and under this grant extended the analysis to the crucial trace element and isotopic SNC signatures. This study then demonstrated the ability to create and end the magnetic field through magma ocean cumulate overturn and subsequent cooling, as well as the feasibility of creating a compositionally- and volumetrically-consistent crustal dichotomy through mode-1 overturn and simultaneous adiabatic melting.

Identification of differentially accumulated proteins associated with embryogenic and non-embryogenic calli in saffron (Crocus sativus L.)

PubMed Central

2012-01-01

Background Somatic embryogenesis (SE) is a complex biological process that occurs under inductive conditions and causes fully differentiated cells to be reprogrammed to an embryo like state. In order to get a better insight about molecular basis of the SE in Crocus sativus L. and to characterize differentially accumulated proteins during the process, a proteomic study based on two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry has been carried out. Results We have compared proteome profiles of non-embryogenic and embryogenic calli with native corm explants. Total soluble proteins were phenol-extracted and loaded on 18 cm IPG strips for the first dimension and 11.5% sodium dodecyl sulfate-polyacrylamide gels for the second dimension. Fifty spots with more than 1.5-fold change in abundance were subjected to mass spectrometry analysis for further characterization. Among them 36 proteins could be identified, which are classified into defense and stress response, protein synthesis and processing, carbohydrate and energy metabolism, secondary metabolism, and nitrogen metabolism. Conclusion Our results showed that diverse cellular and molecular processes were affected during somatic to embryogenic transition. Differential proteomic analysis suggests a key role for ascorbate metabolism during early stage of SE, and points to the possible role of ascorbate-glutathione cycle in establishing somatic embryos. PMID:22243837

Associating Neural Alterations and Genotype in Autism and Fragile X Syndrome: Incorporating Perceptual Phenotypes in Causal Modeling

ERIC Educational Resources Information Center

Bertone, Armando; Hanck, Julie; Kogan, Cary; Chaudhuri, Avi; Cornish, Kim

2010-01-01

We have previously described (see companion paper, this issue) the utility of using perceptual signatures for defining and dissociating condition-specific neural functioning underlying early visual processes in autism and FXS. These perceptually-driven hypotheses are based on differential performance evidenced only at the earliest stages of visual…

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

Biochemistry and Cell Wall Changes Associated with Noni (Morinda citrifolia L.) Fruit Ripening.

PubMed

Cárdenas-Coronel, Wendy G; Carrillo-López, Armando; Vélez de la Rocha, Rosabel; Labavitch, John M; Báez-Sañudo, Manuel A; Heredia, José B; Zazueta-Morales, José J; Vega-García, Misael O; Sañudo-Barajas, J Adriana

2016-01-13

Quality and compositional changes were determined in noni fruit harvested at five ripening stages, from dark-green to thaslucent-grayish. Fruit ripening was accompanied by acidity and soluble solids accumulation but pH diminution, whereas the softening profile presented three differential steps named early (no significant softening), intermediate (significant softening), and final (dramatic softening). At early step the extensive depolymerization of hydrosoluble pectins and the significantly increment of pectinase activities did not correlate with the slight reduction in firmness. The intermediate step showed an increment of pectinases and hemicellulases activities. The final step was accompanied by the most significant reduction in the yield of alcohol-insoluble solids as well as in the composition of uronic acids and neutral sugars; pectinases increased their activity and depolymerization of hemicellulosic fractions occurred. Noni ripening is a process conducted by the coordinated action of pectinases and hemicellulases that promote the differential dissasembly of cell wall polymers.

Pattern of genetic differentiation of an incipient speciation process: The case of the high Andean killifish Orestias

PubMed Central

Guerrero-Jiménez, Claudia Jimena; Peña, Fabiola; Morales, Pamela; Méndez, Marco; Sallaberry, Michel; Vila, Irma; Poulin, Elie

2017-01-01

During the Pleistocene and Holocene, the southwest Andean Altiplano (17°-22°S) was affected by repeated fluctuations in water levels, high volcanic activity and major tectonic movements. In the early Holocene the humid Tauca phase shifted to the arid conditions that have lasted until the present, producing endorheic rivers, lakes, lagoons and wetlands. The endemic fish Orestias (Cyprinodontidae) represents a good model to observe the genetic differentiation that characterizes an incipient speciation process in allopatry since the morphospecies described inhabit a restricted geographic area, with present habitat fragmentation. The genetic diversity and population structure of four endemic morphospecies of Orestias (Cyprinodontidae) found in the Lauca National Park (LNP) analyzed with mitochondrial markers (Control Region) and eight microsatellites, revealed the existence of genetic groups that matches the fragmentation of these systems. High values of genetic and phylogeographic differentiation indices were observed between Chungará Lake and Piacota lagoon. The group composed of the Lauca River, Copapujo and Chuviri wetlands sampling sites showed a clear signal of expansion, with a star-like haplotype network. Levels of genetic differentiation were lower than in Chungará and Piacota, suggesting that these localities would have differentiated after the bottlenecks linked to the collapse of Parinacota volcano. The Parinacota sample showed a population signal that differed from the other localities revealing greater genetic diversity and a disperse network, presenting haplotypes shared with other LNP localities. A mixing pattern of the different genetic groups was evident using the microsatellite markers. The chronology of the vicariance events in LNP may indicate that the partition process of the Orestias populations was gradual. Considering this, and in view of the genetic results, we may conclude that the morphospecies from LNP are populations in ongoing differentiation process. PMID:28245250

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.

Differential effects of parenting in preterm and full-term children on developmental outcomes.

PubMed

Maupin, Angela N; Fine, Jodene Goldenring

2014-12-01

To examine the relations between preterm birth, parenting behavior during early childhood, cognitive development, and social-emotional outcomes at Kindergarten entry, and to determine whether parenting behavior differentially influences this developing system in children born preterm compared to children born full-term. The nationally representative sample comprised 3600 full-term and 1300 preterm children born in the US in the year 2001. All children who entered Kindergarten and who participated in data collection at 9 months, 24 months, and Kindergarten entry were included in the study. Measures of parenting behavior were collected at 9 and 24 months and cognitive development at 24 months via home visits. Social-emotional outcomes were assessed at Kindergarten entry via parent and teacher report. Multiple-sample Structural Equation Modeling was used to analyze group differences in a model whereby early childhood parenting behavior predicted cognitive outcomes, and social-emotional outcomes at Kindergarten entry, and indirectly predicted social-emotional outcomes via early cognitive processes. The full sample developmental model indicated excellent fit to the data. Preterm birth status indirectly influenced social-emotional outcomes at Kindergarten entry via its effect on early childhood parenting behavior and cognitive development. The multi-sample model revealed significant differences in the way in which early parenting behavior exerted its influence on outcomes at Kindergarten entry in preterm children compared to full-term children. For preterm children, parenting indirectly influenced social-emotional outcomes via early cognitive functioning. Findings highlight the importance of early identification and targeted parenting programs to support early cognitive development in preterm children. Copyright © 2014 Elsevier Ltd. All rights reserved.

Time-Series Transcriptomics Reveals That AGAMOUS-LIKE22 Affects Primary Metabolism and Developmental Processes in Drought-Stressed Arabidopsis[OPEN

PubMed Central

Penfold, Christopher A.; Jenkins, Dafyd J.; Legaie, Roxane; Lawson, Tracy; Vialet-Chabrand, Silvere R.M.; Subramaniam, Sunitha; Hickman, Richard; Feil, Regina; Bowden, Laura; Hill, Claire; Lunn, John E.; Finkenstädt, Bärbel; Buchanan-Wollaston, Vicky; Beynon, Jim; Wild, David L.; Ott, Sascha

2016-01-01

In Arabidopsis thaliana, changes in metabolism and gene expression drive increased drought tolerance and initiate diverse drought avoidance and escape responses. To address regulatory processes that link these responses, we set out to identify genes that govern early responses to drought. To do this, a high-resolution time series transcriptomics data set was produced, coupled with detailed physiological and metabolic analyses of plants subjected to a slow transition from well-watered to drought conditions. A total of 1815 drought-responsive differentially expressed genes were identified. The early changes in gene expression coincided with a drop in carbon assimilation, and only in the late stages with an increase in foliar abscisic acid content. To identify gene regulatory networks (GRNs) mediating the transition between the early and late stages of drought, we used Bayesian network modeling of differentially expressed transcription factor (TF) genes. This approach identified AGAMOUS-LIKE22 (AGL22), as key hub gene in a TF GRN. It has previously been shown that AGL22 is involved in the transition from vegetative state to flowering but here we show that AGL22 expression influences steady state photosynthetic rates and lifetime water use. This suggests that AGL22 uniquely regulates a transcriptional network during drought stress, linking changes in primary metabolism and the initiation of stress responses. PMID:26842464

Using sex differences in the developing brain to identify nodes of influence for seizure susceptibility and epileptogenesis.

PubMed

Kight, Katherine E; McCarthy, Margaret M

2014-12-01

Sexual differentiation of the developing brain organizes the neural architecture differently between males and females, and the main influence on this process is exposure to gonadal steroids during sensitive periods of prenatal and early postnatal development. Many molecular and cellular processes are influenced by steroid hormones in the developing brain, including gene expression, cell birth and death, neurite outgrowth and synaptogenesis, and synaptic activity. Perturbations in these processes can alter neuronal excitability and circuit activity, leading to increased seizure susceptibility and the promotion of pathological processes that constitute epileptogenesis. In this review, we will provide a general overview of sex differences in the early developing brain that may be relevant for altered seizure susceptibility in early life, focusing on limbic areas of the brain. Sex differences that have the potential to alter the progress of epileptogenesis are evident at molecular and cellular levels in the developing brain, and include differences in neuronal excitability, response to environmental insult, and epigenetic control of gene expression. Knowing how these processes differ between the sexes can help us understand fundamental mechanisms underlying gender differences in seizure susceptibility and epileptogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

[Effects of temperature on leaf lettuce vernalization.

PubMed

Zhang, Li Li; Hao, Jing Hong; Han, Ying Yan; Liu, Chao Jie; Su, He Nan; Li, Pan Pan; Sun, Yan Chuan; Fan, Shuang Xi

2016-11-18

To investigate the effects of different temperatures on the vernalization of leaf lettuce, and declare their type, two easy bolting leaf lettuce varieties of GB-30 and GB-31 were selected as material, which were treated by 4 ℃, 20 ℃ and 25 ℃ for 20 d respectively and afterwards treated by high temperature stress. The process of flower bud differentiation was observed by using paraffin section technology, and combined the condition of bolting and flowering to estimate whether or not it underwent vernalization, and defined its vernalization type. The results showed that, two varieties of GB-30 and GB-31 appeared bolting to different degrees at the 8 th day under high temperature stress after temperature treatments in the early stage. Different temperatures in the early stage all made flower bud differentiated of two varieties. 4 ℃ treatment did not advance the flower bud differentiation, while the high temperature in later time accelerated this progress. Furthermore, the days required for the two varieties to complete development stages differed under different temperature treatments. The effective accumulated temperature whether from pregermination to flowering or from high temperature stress to flowering of two varieties were also different. The leaf lettuce without low temperature treatment in early stage could enter into the flower bud differentiation, bolting, budding and flowering stages, and it could be considered as non-low temperature vernalization plant. The high temperature treatment in later stage could obviously promote its bolting and flowering. In addition, the effective accumulated temperature had to reach about 2500 ℃·d from germination to blossom.

Propagation of damage in the rat brain following sarin exposure: Differential progression of early processes

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

Lazar, Shlomi; Egoz, Inbal; Brandeis, Rachel

Sarin is an irreversible organophosphate cholinesterase inhibitor and a highly toxic warfare agent. Following the overt, dose-dependent signs (e.g. tremor, hyper secretion, seizures, respiratory depression and eventually death), brain damage is often reported. The goal of the present study was to characterize the early histopathological and biochemical events leading to this damage. Rats were exposed to 1LD50 of sarin (80 μg/kg, i.m.). Brains were removed at 1, 2, 6, 24 and 48 h and processed for analysis. Results showed that TSPO (translocator protein) mRNA increased at 6 h post exposure while TSPO receptor density increased only at 24 h. Inmore » all brain regions tested, bax mRNA decreased 1 h post exposure followed by an increase 24 h later, with only minor increase in bcl2 mRNA. At this time point a decrease was seen in both anti-apoptotic protein Bcl2 and pro-apoptotic Bax, followed by a time and region specific increase in Bax. An immediate elevation in ERK1/2 activity with no change in JNK may indicate an endogenous “first response” mechanism used to attenuate the forthcoming apoptosis. The time dependent increase in the severity of brain damage included an early bi-phasic activation of astrocytes, a sharp decrease in intact neuronal cells, a time dependent reduction in MAP2 and up to 15% of apoptosis. Thus, neuronal death is mostly due to necrosis and severe astrocytosis. The data suggests that timing of possible treatments should be determined by early events following exposure. For example, the biphasic changes in astrocytes activity indicate a possible beneficial effects of delayed anti-inflammatory intervention. - Highlights: • The severity of brain damage post 1LD50 sarin exposure is time dependent. • Sarin induce differential progression of early processes in the rat brain. • Potential treatments should be timed according to early events following exposure. • The biphasic astrocytes activity suggests a delay in anti-inflammatory intervention.« less

The role of early visual cortex in visual short-term memory and visual attention.

PubMed

Offen, Shani; Schluppeck, Denis; Heeger, David J

2009-06-01

We measured cortical activity with functional magnetic resonance imaging to probe the involvement of early visual cortex in visual short-term memory and visual attention. In four experimental tasks, human subjects viewed two visual stimuli separated by a variable delay period. The tasks placed differential demands on short-term memory and attention, but the stimuli were visually identical until after the delay period. Early visual cortex exhibited sustained responses throughout the delay when subjects performed attention-demanding tasks, but delay-period activity was not distinguishable from zero when subjects performed a task that required short-term memory. This dissociation reveals different computational mechanisms underlying the two processes.

Thermal evolution of magma reservoirs in the shallow crust and incidence on magma differentiation: the St-Jean-du-Doigt layered intrusion (Brittany, France)

NASA Astrophysics Data System (ADS)

Barboni, M.; Bussy, F.; Ovtcharova, M.; Schoene, B.

2009-12-01

Understanding the emplacement and growth of intrusive bodies in terms of mechanism, duration, thermal evolution and rates are fundamental aspects of crustal evolution. Recent studies show that many plutons grow in several Ma by in situ accretion of discrete magma pulses, which constitute small-scale magmatic reservoirs. The residence time of magmas, and hence their capacities to interact and differentiate, are controlled by the local thermal environment. The latter is highly dependant on 1) the emplacement depth, 2) the magmas and country rock composition, 3) the country rock thermal conductivity, 4) the rate of magma injection and 5) the geometry of the intrusion. In shallow level plutons, where magmas solidify quickly, evidence for magma mixing and/or differentiation processes is considered by many authors to be inherited from deeper levels. We show however that in-situ differentiation and magma interactions occurred within basaltic and felsic sills at shallow depth (0.3 GPa) in the St-Jean-du-Doigt bimodal intrusion, France. Field evidence coupled to high precision zircon U-Pb dating document progressive thermal maturation within the incrementally built laccolith. Early m-thick mafic sills are homogeneous and fine-grained with planar contacts with neighbouring felsic sills; within a minimal 0.5 Ma time span, the system gets warmer, adjacent sills interact and mingle, and mafic sills are differentiating in the top 40 cm of the layer. Rheological and thermal modelling show that observed in-situ differentiation-accumulation processes may be achieved in less than 10 years at shallow depth, provided that (1) the differentiating sills are injected beneath consolidated, yet still warm basalt sills, which act as low conductive insulating screens, (2) the early mafic sills accreted under the roof of the laccolith as a 100m thick top layer within 0.5 My, and (3) subsequent and sustained magmatic activity occurred on a short time scale (years) at an injection rate of ca. 0.5m/y. Extraction of differentiated residual liquids might eventually take place and mix with newly injected magma as documented in active syn-emplacement shear-zones. These low-pressure differentiated liquids can potentially contribute to subaerial volcanic activity along the major shear-zones.

Development, epigenetics and metabolic programming

PubMed Central

Godfrey, Keith M; Costello, Paula; Lillycrop, Karen

2016-01-01

It is now widely recognised that the environment in early life can have important effects on human growth and development, including the “programming” of far reaching effects on the risk of developing common metabolic and other non-communicable diseases in later life. We have shown that greater childhood adiposity is associated with higher maternal adiposity, low maternal vitamin D status, excessive gestational weight gain, and short duration of breastfeeding; maternal dietary patterns in pregnancy and vitamin D status have been linked with childhood bone mineral content and muscle function. Human studies have identified fetal liver blood flow adaptations and epigenetic changes as potential mechanisms that could link maternal influences with offspring body composition. In experimental studies there is now substantial evidence that the environment during early life induces altered phenotypes through epigenetic mechanisms. Epigenetic processes such as DNA methylation, covalent modifications of histones and non-coding RNAs can induce changes in gene expression without a change in DNA base sequence. Such processes are involved in cell differentiation and genomic imprinting, as well as the phenomenon of developmental plasticity in response to environmental influences. Elucidation of such epigenetic processes may enable early intervention strategies to improve early development and growth. PMID:27088334

Early development of the circumferential axonal pathway in mouse and chick spinal cord.

PubMed

Holley, J A

1982-03-10

The early development of the circumferential axonal pathway in the brachial and lumbar spinal cord of mouse and chick embryos was studied by scanning and transmission electron microscopy. The cellular processes which comprise this pathway grow in the transverse plane and along the lateral margin of the marginal zone (i.e., circumferentially oriented), as typified by the early embryonic commissural axons. The first formative event observed was in the ventrolateral margin of the primitive spinal cord ventricular zone. Cellular processes were found near the external limiting membrane that appeared to grow a variable distance either dorsally or ventrally. Later in development, presumptive motor column neurons migrated into the ventrolateral region, distal to these early circumferentially oriented processes. Concurrently, other circumferentially oriented perikarya and processes appeared along the dorsolateral margin. Due to their aligned sites of origin and parallel growth, the circumferential processes formed a more or less continuous line or pathway, which in about 10% of the scanned specimens could be followed along the entire lateral margin of the embryonic spinal cord. Several specimens later in development had two sets of aligned circumferential processes in the ventral region. Large numbers of circumferential axons were then found to follow the preformed pathway by fasciculation, after the primitive motor column had become established. Since the earliest circumferential processes appeared to differentiate into axons and were found nearly 24 hours prior to growth of most circumferential axons, their role in guidance as pioneering axons was suggested.

Long-term academic stress enhances early processing of facial expressions.

PubMed

Zhang, Liang; Qin, Shaozheng; Yao, Zhuxi; Zhang, Kan; Wu, Jianhui

2016-11-01

Exposure to long-term stress can lead to a variety of emotional and behavioral problems. Although widely investigated, the neural basis of how long-term stress impacts emotional processing in humans remains largely elusive. Using event-related brain potentials (ERPs), we investigated the effects of long-term stress on the neural dynamics of emotionally facial expression processing. Thirty-nine male college students undergoing preparation for a major examination and twenty-one matched controls performed a gender discrimination task for faces displaying angry, happy, and neutral expressions. The results of the Perceived Stress Scale showed that participants in the stress group perceived higher levels of long-term stress relative to the control group. ERP analyses revealed differential effects of long-term stress on two early stages of facial expression processing: 1) long-term stress generally augmented posterior P1 amplitudes to facial stimuli irrespective of expression valence, suggesting that stress can increase sensitization to visual inputs in general, and 2) long-term stress selectively augmented fronto-central P2 amplitudes for angry but not for neutral or positive facial expressions, suggesting that stress may lead to increased attentional prioritization to processing negative emotional stimuli. Together, our findings suggest that long-term stress has profound impacts on the early stages of facial expression processing, with an increase at the very early stage of general information inputs and a subsequent attentional bias toward processing emotionally negative stimuli. Copyright © 2016 Elsevier B.V. All rights reserved.

Transcriptomic Analysis of Differentially Expressed Genes During Larval Development of Rapana venosa by Digital Gene Expression Profiling.

PubMed

Song, Hao; Yu, Zheng-Lin; Sun, Li-Na; Xue, Dong-Xiu; Zhang, Tao; Wang, Hai-Yan

2016-07-07

During the life cycle of shellfish, larval development, especially metamorphosis, has a vital influence on the dynamics, distribution, and recruitment of natural populations, as well as seed breeding. Rapana venosa, a carnivorous gastropod, is an important commercial shellfish in China, and is an ecological invader in the United States, Argentina, and France. However, information about the mechanism of its early development is still limited, because research in this area has long suffered from a lack of genomic resources. In this study, 15 digital gene expression (DGE) libraries from five developmental stages of R. venosa were constructed and sequenced on the IIIumina Hi-Sequation 2500 platform. Bioinformaticsanalysis identified numerous differentially and specifically expressed genes, which revealed that genes associated with growth, nervous system, digestive system, immune system, and apoptosis participate in important developmental processes. The functional analysis of differentially expressed genes was further implemented by gene ontology, and Kyoto encyclopedia of genes and genomes enrichment. DGE profiling provided a general picture of the transcriptomic activities during the early development of R. venosa, which may provide interesting hints for further study. Our data represent the first comparative transcriptomic information available for the early development of R. venosa, which is a prerequisite for a better understanding of the physiological traits controlling development. Copyright © 2016 Song et al.

Generation of monoclonal antibodies specific for cell surface molecules expressed on early mouse endoderm.

PubMed

Gadue, Paul; Gouon-Evans, Valerie; Cheng, Xin; Wandzioch, Ewa; Zaret, Kenneth S; Grompe, Markus; Streeter, Philip R; Keller, Gordon M

2009-09-01

The development of functional cell populations such as hepatocytes and pancreatic beta cells from embryonic stem cell (ESC) is dependent on the efficient induction of definitive endoderm early in the differentiation process. To monitor definitive endoderm formation in mouse ESC differentiation cultures in a quantitative fashion, we generated a reporter cell line that expresses human CD25 from the Foxa3 locus and human CD4 from the Foxa2 locus. Induction of these reporter ESCs with high concentrations of activin A led to the development of a CD25-Foxa3+CD4-Foxa2+ population within 4-5 days of culture. Isolation and characterization of this population showed that it consists predominantly of definitive endoderm that is able to undergo hepatic specification under the appropriate conditions. To develop reagents that can be used for studies on endoderm development from unmanipulated ESCs, from induced pluripotent stem cells, and from the mouse embryo, we generated monoclonal antibodies against the CD25-Foxa3+CD4-Foxa2+ population. With this approach, we identified two antibodies that react specifically with endoderm from ESC cultures and from the early embryo. The specificity of these antibodies enables one to quantitatively monitor endoderm development in ESC differentiation cultures, to study endoderm formation in the embryo, and to isolate pure populations of culture- or embryo-derived endodermal cells.

Gravitropism of cut shoots is mediated by oxidative processes: A physiological and molecular study

NASA Astrophysics Data System (ADS)

Philosoph-Hadas, Sonia; Friedman, Haya; Meir, Shimon

2012-07-01

The signal transduction events occurring during shoot gravitropism are mediated through amyloplasts sedimentation, reorientation of actin filaments in the endodermis, and differential changes in level and action of auxin, associated with differential growth leading to shoot curvature. Since increase in reactive oxygen species (ROS) was shown to be associated with growth, we examined the possible use of antioxidants in controlling the gravitropic response, via their interaction with events preceding shoot bending. Reoriented snapdragon (Antirrhinum majus L.) spikes and tomato (Solanum lycopersicum cv. MicroTom) shoots showed a visual upward bending after a lag period of 3 or 5 h, respectively, which was inhibited by the antioxidants N-acetyl-cysteine (NAC) and reduced glutathione (GSH). This suggests the involvement of oxidative reactions in the process. The two antioxidants prevented the sedimentation of amyloplasts to the bottom of the endodermis cells following 0.5-5 h of snapdragon shoot reorientation, suggesting that oxidative reactions are involved already at a very early signal perception stage prior to the visual bending. In addition, a differential distribution in favor of the lower shoot side of various oxidative elements, including H2O2 concentrations and activity of the NADPH-oxidase enzyme, was observed during reorientation of snapdragon spikes. Application of the two antioxidants reduced the levels of these elements and abolished their differential distribution across the shoot. On the other hand, the activity of the antioxidative enzyme, superoxide dismutase (SOD), which was not differentially distributed across the shoot, increased significantly following application of the two antioxidants. The auxin redistribution in reoriented shoots was analyzed using transgenic tomato plants expressing the GUS reporter gene under the Aux/IAA4 promoter (a generous gift of M. Bouzayen, France). GUS response, detected in control shoots 4 h after their reorientation in favor of the lower shoot side was completely eliminated in the NAC-treated shoots, in which the bending response was inhibited. These results suggest that the gravitropic-induced asymmetric auxin redistribution precedes shoot bending, and NAC inhibits this response by abolishing the auxin gradient across the shoot. Our microarray analysis of tomato shoots, using the Affymetrix Tomato GeneChip, revealed differential changes in expression of 266 genes, occurring during the initial 0.5-5 h of shoot reorientation prior to bending. The differential changes in expression of auxin-related genes in favor of the lower shoot side occurred already following 0.5 h of reorientation, while those of cell wall-related genes, associated with shoot bending, occurred only 3 h following shoot reorientation. Among the identified genes, 11 genes were related to auxin, and 36 genes were associated with oxidative processes, demonstrating the involvement of ROS in early events of shoot gravitropism. Taken together, our results suggest that ROS mediate the early gravity-induced amyloplast sedimentation required for signal perception, as well as the lateral auxin movement across the shoot, which is necessary for the auxin asymmetric distribution leading to shoot upward bending.

A nonmagnetic differentiated early planetary body

DOE PAGES

Weiss, Benjamin P.; Wang, Huapei; Sharp, Thomas G.; ...

2017-06-19

Paleomagnetic studies of meteorites have shown that the solar nebula was likely magnetized and that many early planetary bodies generated dynamo magnetic fields in their advecting metallic cores. The surface fields on these bodies were recorded by a diversity of chondrites and achondrites, ranging in intensity from several μT to several hundred μT. In fact, an achondrite parent body without evidence for paleomagnetic fields has yet to be confidently identified, hinting that early solar system field generation and the dynamo process in particular may have been common. Here we present paleomagnetic measurements of the ungrouped achondrite NWA 7325 indicating thatmore » it last cooled in a near-zero field (<~1.7μT), estimated to have occurred at 4563.09 ± 0.26 million years ago (Ma) from Al–Mg chronometry. Because NWA 7325 is highly depleted in siderophile elements, its parent body nevertheless underwent large-scale metal-silicate differentiation and likely formed a metallic core. This makes NWA 7325 the first recognized example of an essentially unmagnetized igneous rock from a differentiated early solar system body. These results indicate that all magnetic fields, including those from any core dynamo on the NWA 7325 parent body, the solar nebula, young Sun, and solar wind, were <1.7 μT at the location of NWA 7325 at 4563 Ma. Finally, this supports a recent conclusion that the solar nebula had dissipated by ~4 million years after solar system formation. NWA 7325 also serves as an experimental control that gives greater confidence in the positive identification of remanent magnetization in other achondrites.« less

A nonmagnetic differentiated early planetary body

NASA Astrophysics Data System (ADS)

Weiss, Benjamin P.; Wang, Huapei; Sharp, Thomas G.; Gattacceca, Jérôme; Shuster, David L.; Downey, Brynna; Hu, Jinping; Fu, Roger R.; Kuan, Aaron T.; Suavet, Clément; Irving, Anthony J.; Wang, Jun; Wang, Jiajun

2017-06-01

Paleomagnetic studies of meteorites have shown that the solar nebula was likely magnetized and that many early planetary bodies generated dynamo magnetic fields in their advecting metallic cores. The surface fields on these bodies were recorded by a diversity of chondrites and achondrites, ranging in intensity from several μT to several hundred μT. In fact, an achondrite parent body without evidence for paleomagnetic fields has yet to be confidently identified, hinting that early solar system field generation and the dynamo process in particular may have been common. Here we present paleomagnetic measurements of the ungrouped achondrite NWA 7325 indicating that it last cooled in a near-zero field (<∼1.7 μT), estimated to have occurred at 4563.09 ± 0.26 million years ago (Ma) from Al-Mg chronometry. Because NWA 7325 is highly depleted in siderophile elements, its parent body nevertheless underwent large-scale metal-silicate differentiation and likely formed a metallic core. This makes NWA 7325 the first recognized example of an essentially unmagnetized igneous rock from a differentiated early solar system body. These results indicate that all magnetic fields, including those from any core dynamo on the NWA 7325 parent body, the solar nebula, young Sun, and solar wind, were <1.7 μT at the location of NWA 7325 at 4563 Ma. This supports a recent conclusion that the solar nebula had dissipated by ∼4 million years after solar system formation. NWA 7325 also serves as an experimental control that gives greater confidence in the positive identification of remanent magnetization in other achondrites.

Small RNA Sequencing Reveals Differential miRNA Expression in the Early Development of Broccoli (Brassica oleracea var. italica) Pollen

PubMed Central

Li, Hui; Wang, Yu; Wu, Mei; Li, Lihong; Jin, Chuan; Zhang, Qingli; Chen, Chengbin; Song, Wenqin; Wang, Chunguo

2017-01-01

Pollen development is an important and complex biological process in the sexual reproduction of flowering plants. Although the cytological characteristics of pollen development are well defined, the regulation of its early stages remains largely unknown. In the present study, miRNAs were explored in the early development of broccoli (Brassica oleracea var. italica) pollen. A total of 333 known miRNAs that originated from 235 miRNA families were detected. Fifty-five novel miRNA candidates were identified. Sixty of the 333 known miRNAs and 49 of the 55 predicted novel miRNAs exhibited significantly differential expression profiling in the three distinct developmental stages of broccoli pollen. Among these differentially expressed miRNAs, miRNAs that would be involved in the developmental phase transition from uninucleate microspores to binucleate pollen grains or from binucleate to trinucleate pollen grains were identified. miRNAs that showed significantly enriched expression in a specific early stage of broccoli pollen development were also observed. In addition, 552 targets for 127 known miRNAs and 69 targets for 40 predicted novel miRNAs were bioinformatically identified. Functional annotation and GO (Gene Ontology) analysis indicated that the putative miRNA targets showed significant enrichment in GO terms that were related to plant organ formation and morphogenesis. Some of enriched GO terms were detected for the targets directly involved in plant male reproduction development. These findings provided new insights into the functions of miRNA-mediated regulatory networks in broccoli pollen development. PMID:28392797

Small RNA Sequencing Reveals Differential miRNA Expression in the Early Development of Broccoli (Brassica oleracea var. italica) Pollen.

PubMed

Li, Hui; Wang, Yu; Wu, Mei; Li, Lihong; Jin, Chuan; Zhang, Qingli; Chen, Chengbin; Song, Wenqin; Wang, Chunguo

2017-01-01

Pollen development is an important and complex biological process in the sexual reproduction of flowering plants. Although the cytological characteristics of pollen development are well defined, the regulation of its early stages remains largely unknown. In the present study, miRNAs were explored in the early development of broccoli ( Brassica oleracea var. italica ) pollen. A total of 333 known miRNAs that originated from 235 miRNA families were detected. Fifty-five novel miRNA candidates were identified. Sixty of the 333 known miRNAs and 49 of the 55 predicted novel miRNAs exhibited significantly differential expression profiling in the three distinct developmental stages of broccoli pollen. Among these differentially expressed miRNAs, miRNAs that would be involved in the developmental phase transition from uninucleate microspores to binucleate pollen grains or from binucleate to trinucleate pollen grains were identified. miRNAs that showed significantly enriched expression in a specific early stage of broccoli pollen development were also observed. In addition, 552 targets for 127 known miRNAs and 69 targets for 40 predicted novel miRNAs were bioinformatically identified. Functional annotation and GO (Gene Ontology) analysis indicated that the putative miRNA targets showed significant enrichment in GO terms that were related to plant organ formation and morphogenesis. Some of enriched GO terms were detected for the targets directly involved in plant male reproduction development. These findings provided new insights into the functions of miRNA-mediated regulatory networks in broccoli pollen development.

Weighted gene co-expression network analysis reveals potential genes involved in early metamorphosis process in sea cucumber Apostichopus japonicus.

PubMed

Li, Yongxin; Kikuchi, Mani; Li, Xueyan; Gao, Qionghua; Xiong, Zijun; Ren, Yandong; Zhao, Ruoping; Mao, Bingyu; Kondo, Mariko; Irie, Naoki; Wang, Wen

2018-01-01

Sea cucumbers, one main class of Echinoderms, have a very fast and drastic metamorphosis process during their development. However, the molecular basis under this process remains largely unknown. Here we systematically examined the gene expression profiles of Japanese common sea cucumber (Apostichopus japonicus) for the first time by RNA sequencing across 16 developmental time points from fertilized egg to juvenile stage. Based on the weighted gene co-expression network analysis (WGCNA), we identified 21 modules. Among them, MEdarkmagenta was highly expressed and correlated with the early metamorphosis process from late auricularia to doliolaria larva. Furthermore, gene enrichment and differentially expressed gene analysis identified several genes in the module that may play key roles in the metamorphosis process. Our results not only provide a molecular basis for experimentally studying the development and morphological complexity of sea cucumber, but also lay a foundation for improving its emergence rate. Copyright © 2017 Elsevier Inc. All rights reserved.

Tracing the first step to speciation: ecological and genetic differentiation of a salamander population in a small forest.

PubMed

Steinfartz, Sebastian; Weitere, Markus; Tautz, Diethard

2007-11-01

Mechanisms and processes of ecologically driven adaptive speciation are best studied in natural situations where the splitting process is still occurring, i.e. before complete reproductive isolation is achieved. Here, we present a case of an early stage of adaptive differentiation under sympatric conditions in the fire salamander, Salamandra salamandra, that allows inferring the underlying processes for the split. Larvae of S. salamandra normally mature in small streams until metamorphosis, but in an old, continuous forest area near Bonn (the Kottenforst), we found salamander larvae not only in small streams but also in shallow ponds, which are ecologically very different from small streams. Common-environment experiments with larvae from both habitat types reveal specific adaptations to these different ecological conditions. Mitochondrial and microsatellite analyses show that the two ecologically differentiated groups also show signs of genetic differentiation. A parallel analysis of animals from a neighbouring much larger forest area (the Eifel), in which larvae mature only in streams, shows no signs of genetic differentiation, indicating that gene flow between ecologically similar types can occur over large distances. Hence, geographical factors cannot explain the differential larval habitat adaptations in the Kottenforst, in particular since adult life and mating of S. salamandra is strictly terrestrial and not associated with larval habitats. We propose therefore that the evolution of these adaptations was coupled with the evolution of cues for assortative mating which would be in line with models of sympatric speciation that suggest a co-evolution of habitat adaptations and associated mating signals.

Gene function in early mouse embryonic stem cell differentiation

PubMed Central

Sene, Kagnew Hailesellasse; Porter, Christopher J; Palidwor, Gareth; Perez-Iratxeta, Carolina; Muro, Enrique M; Campbell, Pearl A; Rudnicki, Michael A; Andrade-Navarro, Miguel A

2007-01-01

Background Little is known about the genes that drive embryonic stem cell differentiation. However, such knowledge is necessary if we are to exploit the therapeutic potential of stem cells. To uncover the genetic determinants of mouse embryonic stem cell (mESC) differentiation, we have generated and analyzed 11-point time-series of DNA microarray data for three biologically equivalent but genetically distinct mESC lines (R1, J1, and V6.5) undergoing undirected differentiation into embryoid bodies (EBs) over a period of two weeks. Results We identified the initial 12 hour period as reflecting the early stages of mESC differentiation and studied probe sets showing consistent changes of gene expression in that period. Gene function analysis indicated significant up-regulation of genes related to regulation of transcription and mRNA splicing, and down-regulation of genes related to intracellular signaling. Phylogenetic analysis indicated that the genes showing the largest expression changes were more likely to have originated in metazoans. The probe sets with the most consistent gene changes in the three cell lines represented 24 down-regulated and 12 up-regulated genes, all with closely related human homologues. Whereas some of these genes are known to be involved in embryonic developmental processes (e.g. Klf4, Otx2, Smn1, Socs3, Tagln, Tdgf1), our analysis points to others (such as transcription factor Phf21a, extracellular matrix related Lama1 and Cyr61, or endoplasmic reticulum related Sc4mol and Scd2) that have not been previously related to mESC function. The majority of identified functions were related to transcriptional regulation, intracellular signaling, and cytoskeleton. Genes involved in other cellular functions important in ESC differentiation such as chromatin remodeling and transmembrane receptors were not observed in this set. Conclusion Our analysis profiles for the first time gene expression at a very early stage of mESC differentiation, and identifies a functional and phylogenetic signature for the genes involved. The data generated constitute a valuable resource for further studies. All DNA microarray data used in this study are available in the StemBase database of stem cell gene expression data [1] and in the NCBI's GEO database. PMID:17394647

Constraints on Martian Differentiation Processes from Rb-Sr and Sm-Nd Isotopic Analyses of the Basaltic Shergottite QUE 94201

NASA Technical Reports Server (NTRS)

Borg, Lars E.; Nyquist, Larry E.; Taylor, Larry A.; Wiesmann, Henry; Shih, Chi-Y.

1997-01-01

Isotopic analyses of mineral, leachate, and whole rock fractions from the Martian shergottite meteorite QUE 94201 yield Rb-Sr and Sm-Nd crystallization ages of 327 +/- 12 and 327 +/- 19 Ma, respectively. These ages are concordant, although the isochrons are defined by different fractions within the meteorite. Comparison of isotope dilution Sm and Nd data for the various QUE 94201 fractions with in situ ion microprobe data for QUE 94201 minerals from the literature demonstrate the presence of a leachable crustal component in the meteorite. This component is likely to have been added to QUE 94201 by secondary alteration processes on Mars, and can affect the isochrons by selectively altering the isotopic systematics of the leachates and some of the mineral fractions. The absence of crustal recycling processes on Mars may preserve the geochemical evidence for early differentiation and the decoupling of the Rb-Sr and Sm-Nd isotopic systems, underscoring one of the fundamental differences between geologic processes on Mars and the Earth.

Structural face encoding: How task affects the N170's sensitivity to race.

PubMed

Senholzi, Keith B; Ito, Tiffany A

2013-12-01

The N170 event-related potential (ERP) component differentiates faces from non-faces, but studies aimed at investigating whether the processing indexed by this component is also sensitive to racial differences among faces have garnered conflicting results. Here, we explore how task affects the influence of race on the N170 among White participants. N170s were larger to ingroup White faces than outgroup Black faces, but only for those required to attend to race, suggesting that attention to race can result in deeper levels of processing for ingroup members. Conversely, N170s were larger to Black faces than White faces for participants who attended to the unique identity of the faces, suggesting that attention to identity can result in preferential recruitment of cognitive resources for outgroup members. Taken together, these findings suggest that race can differentially impact face processing at early stages of encoding, but differences in processing are contingent upon one's goal state.

Low oxygen tension enhances endothelial fate of human pluripotent stem cells.

PubMed

Kusuma, Sravanti; Peijnenburg, Elizabeth; Patel, Parth; Gerecht, Sharon

2014-04-01

A critical regulator of the developing or regenerating vasculature is low oxygen tension. Precise elucidation of the role of low oxygen environments on endothelial commitment from human pluripotent stem cells necessitates controlled in vitro differentiation environments. We used a feeder-free, 2-dimensional differentiation system in which we could monitor accurately dissolved oxygen levels during human pluripotent stem cell differentiation toward early vascular cells (EVCs). We found that oxygen uptake rate of differentiating human pluripotent stem cells is lower in 5% O2 compared with atmospheric conditions. EVCs differentiated in 5% O2 had an increased vascular endothelial cadherin expression with clusters of vascular endothelial cadherin+ cells surrounded by platelet-derived growth factor β+ cells. When we assessed the temporal effects of low oxygen differentiation environments, we determined that low oxygen environments during the early stages of EVC differentiation enhance endothelial lineage commitment. EVCs differentiated in 5% O2 exhibited an increased expression of vascular endothelial cadherin and CD31 along with their localization to the membrane, enhanced lectin binding and acetylated low-density lipoprotein uptake, rapid cord-like structure formation, and increased expression of arterial endothelial cell markers. Inhibition of reactive oxygen species generation during the early stages of differentiation abrogated the endothelial inductive effects of the low oxygen environments. Low oxygen tension during early stages of EVC derivation induces endothelial commitment and maturation through the accumulation of reactive oxygen species, highlighting the importance of regulating oxygen tensions during human pluripotent stem cell-vascular differentiation.

Tumor Necrosis Factor Alpha and Insulin-Like Growth Factor 1 Induced Modifications of the Gene Expression Kinetics of Differentiating Skeletal Muscle Cells

PubMed Central

Meyer, Swanhild U.; Krebs, Stefan; Thirion, Christian; Blum, Helmut; Krause, Sabine; Pfaffl, Michael W.

2015-01-01

Introduction TNF-α levels are increased during muscle wasting and chronic muscle degeneration and regeneration processes, which are characteristic for primary muscle disorders. Pathologically increased TNF-α levels have a negative effect on muscle cell differentiation efficiency, while IGF1 can have a positive effect; therefore, we intended to elucidate the impact of TNF-α and IGF1 on gene expression during the early stages of skeletal muscle cell differentiation. Methodology/Principal Findings This study presents gene expression data of the murine skeletal muscle cells PMI28 during myogenic differentiation or differentiation with TNF-α or IGF1 exposure at 0 h, 4 h, 12 h, 24 h, and 72 h after induction. Our study detected significant coregulation of gene sets involved in myoblast differentiation or in the response to TNF-α. Gene expression data revealed a time- and treatment-dependent regulation of signaling pathways, which are prominent in myogenic differentiation. We identified enrichment of pathways, which have not been specifically linked to myoblast differentiation such as doublecortin-like kinase pathway associations as well as enrichment of specific semaphorin isoforms. Moreover to the best of our knowledge, this is the first description of a specific inverse regulation of the following genes in myoblast differentiation and response to TNF-α: Aknad1, Cmbl, Sepp1, Ndst4, Tecrl, Unc13c, Spats2l, Lix1, Csdc2, Cpa1, Parm1, Serpinb2, Aspn, Fibin, Slc40a1, Nrk, and Mybpc1. We identified a gene subset (Nfkbia, Nfkb2, Mmp9, Mef2c, Gpx, and Pgam2), which is robustly regulated by TNF-α across independent myogenic differentiation studies. Conclusions This is the largest dataset revealing the impact of TNF-α or IGF1 treatment on gene expression kinetics of early in vitro skeletal myoblast differentiation. We identified novel mRNAs, which have not yet been associated with skeletal muscle differentiation or response to TNF-α. Results of this study may facilitate the understanding of transcriptomic networks underlying inhibited muscle differentiation in inflammatory diseases. PMID:26447881

Epimorphin acts extracellularly to promote cell sorting and aggregation during the condensation of vertebral cartilage.

PubMed

Oka, Yumiko; Sato, Yuki; Tsuda, Hokari; Hanaoka, Kazunori; Hirai, Yohei; Takahashi, Yoshiko

2006-03-01

Formation of vertebrae occurs via endochondral ossification, a process involving condensation of precartilaginous cells. Here, we provide the first molecular evidence of mechanism that underlies initiation of this process by showing that the extracellular factor, Epimorphin, plays a role during early steps in vertebral cartilage condensation. Epimorphin mRNA is predominantly localized in the vertebral primordium. When provided exogenously in ovo, it causes precocious differentiation of chondrocytes, resulting in the formation of supernumerary vertebral cartilage in chicken embryos. To further analyze its mode of action, we used an in vitro co-culture system in which labeled 10T1/2 or sclerotomal prechondrogenic cells were co-cultured with unlabeled Epimorphin-producing cells. In the presence of Epimorphin, the labeled cells formed tightly packed aggregates, and sclerotomal cells displayed augmented accumulation of NCAM and other early markers of chondrocyte differentiation. Finally, we found that the Epimorphin expression is initiated during vertebrogenesis by Sonic hedgehog from the notochord mediated by Sox 9. We present a model in which successive action of Epimorphin in recruiting and stacking sclerotomal cells leads to a sequential elongation of a vertebral primordium.

Sustained neural activity to gaze and emotion perception in dynamic social scenes

PubMed Central

Ulloa, José Luis; Puce, Aina; Hugueville, Laurent; George, Nathalie

2014-01-01

To understand social interactions, we must decode dynamic social cues from seen faces. Here, we used magnetoencephalography (MEG) to study the neural responses underlying the perception of emotional expressions and gaze direction changes as depicted in an interaction between two agents. Subjects viewed displays of paired faces that first established a social scenario of gazing at each other (mutual attention) or gazing laterally together (deviated group attention) and then dynamically displayed either an angry or happy facial expression. The initial gaze change elicited a significantly larger M170 under the deviated than the mutual attention scenario. At around 400 ms after the dynamic emotion onset, responses at posterior MEG sensors differentiated between emotions, and between 1000 and 2200 ms, left posterior sensors were additionally modulated by social scenario. Moreover, activity on right anterior sensors showed both an early and prolonged interaction between emotion and social scenario. These results suggest that activity in right anterior sensors reflects an early integration of emotion and social attention, while posterior activity first differentiated between emotions only, supporting the view of a dual route for emotion processing. Altogether, our data demonstrate that both transient and sustained neurophysiological responses underlie social processing when observing interactions between others. PMID:23202662

Regulation of cambial activity in relation to environmental conditions: understanding the role of temperature in wood formation of trees.

PubMed

Begum, Shahanara; Nakaba, Satoshi; Yamagishi, Yusuke; Oribe, Yuichiro; Funada, Ryo

2013-01-01

The timing of cambial reactivation plays an important role in determination of the amount and quality of wood and the environmental adaptivity of trees. Environmental factors, such as temperature, influence the growth and development of trees. Temperatures from late winter to early spring affect the physiological processes that are involved in the initiation of cambial cell division and xylem differentiation in trees. Cumulative elevated temperatures from late winter to early spring result in earlier initiation of cambial reactivation and xylem differentiation in tree stems and an extended growth period. However, earlier cambial reactivation increases the risk for frost damage because the cold tolerance of cambium decreases after cambial reactivation. The present review focuses on temperature regulation on the timing of cambial reactivation and xylem differentiation in trees, and also highlights recent advances in our understanding of seasonal changes in the cold stability of microtubules in trees. The review also summarizes the present understanding of the relationships between the timing of cambial reactivation, the start of xylem differentiation and changes in levels of storage materials in trees, as well as an attempt to identify the source of energy for cell division and differentiation. A better understanding of the mechanisms that regulate wood formation in trees and the influence of environmental conditions on such mechanisms should help in efforts to improve and enhance the exploitation of wood for commercial applications and to prepare for climatic change. Copyright © Physiologia Plantarum 2012.

FGF-Dependent, Context-Driven Role for FRS Adapters in the Early Telencephalon

PubMed Central

Gutin, Grigoriy; Blackwood, Christopher A.; Kamatkar, Nachiket G.; Lee, Kyung W.; Fishell, Gordon; Wang, Fen

2017-01-01

FGF signaling, an important component of intercellular communication, is required in many tissues throughout development to promote diverse cellular processes. Whether FGF receptors (FGFRs) accomplish such varied tasks in part by activating different intracellular transducers in different contexts remains unclear. Here, we used the developing mouse telencephalon as an example to study the role of the FRS adapters FRS2 and FRS3 in mediating the functions of FGFRs. Using tissue-specific and germline mutants, we examined the requirement of Frs genes in two FGFR-dependent processes. We found that Frs2 and Frs3 are together required for the differentiation of a subset of medial ganglionic eminence (MGE)-derived neurons, but are dispensable for the survival of early telencephalic precursor cells, in which any one of three FGFRs (FGFR1, FGFR2, or FGFR3) is sufficient for survival. Although FRS adapters are dispensable for ERK-1/2 activation, they are required for AKT activation within the subventricular zone of the developing MGE. Using an FRS2,3-binding site mutant of Fgfr1, we established that FRS adapters are necessary for mediating most or all FGFR1 signaling, not only in MGE differentiation, but also in cell survival, implying that other adapters mediate at least in part the signaling from FGFR2 and FGFR3. Our study provides an example of a contextual role for an intracellular transducer and contributes to our understanding of how FGF signaling plays diverse developmental roles. SIGNIFICANCE STATEMENT FGFs promote a range of developmental processes in many developing tissues and at multiple developmental stages. The mechanisms underlying this multifunctionality remain poorly defined in vivo. Using telencephalon development as an example, we show here that FRS adapters exhibit some selectivity in their requirement for mediating FGF receptor (FGFR) signaling and activating downstream mediators that depend on the developmental process, with a requirement in neuronal differentiation but not cell survival. Differential engagement of FRS and non-FRS intracellular adapters downstream of FGFRs could therefore in principle explain how FGFs play several distinct roles in other developing tissues and developmental stages. PMID:28483978

FGF-Dependent, Context-Driven Role for FRS Adapters in the Early Telencephalon.

PubMed

Nandi, Sayan; Gutin, Grigoriy; Blackwood, Christopher A; Kamatkar, Nachiket G; Lee, Kyung W; Fishell, Gordon; Wang, Fen; Goldfarb, Mitchell; Hébert, Jean M

2017-06-07

FGF signaling, an important component of intercellular communication, is required in many tissues throughout development to promote diverse cellular processes. Whether FGF receptors (FGFRs) accomplish such varied tasks in part by activating different intracellular transducers in different contexts remains unclear. Here, we used the developing mouse telencephalon as an example to study the role of the FRS adapters FRS2 and FRS3 in mediating the functions of FGFRs. Using tissue-specific and germline mutants, we examined the requirement of Frs genes in two FGFR-dependent processes. We found that Frs2 and Frs3 are together required for the differentiation of a subset of medial ganglionic eminence (MGE)-derived neurons, but are dispensable for the survival of early telencephalic precursor cells, in which any one of three FGFRs (FGFR1, FGFR2, or FGFR3) is sufficient for survival. Although FRS adapters are dispensable for ERK-1/2 activation, they are required for AKT activation within the subventricular zone of the developing MGE. Using an FRS2,3-binding site mutant of Fgfr1 , we established that FRS adapters are necessary for mediating most or all FGFR1 signaling, not only in MGE differentiation, but also in cell survival, implying that other adapters mediate at least in part the signaling from FGFR2 and FGFR3. Our study provides an example of a contextual role for an intracellular transducer and contributes to our understanding of how FGF signaling plays diverse developmental roles. SIGNIFICANCE STATEMENT FGFs promote a range of developmental processes in many developing tissues and at multiple developmental stages. The mechanisms underlying this multifunctionality remain poorly defined in vivo Using telencephalon development as an example, we show here that FRS adapters exhibit some selectivity in their requirement for mediating FGF receptor (FGFR) signaling and activating downstream mediators that depend on the developmental process, with a requirement in neuronal differentiation but not cell survival. Differential engagement of FRS and non-FRS intracellular adapters downstream of FGFRs could therefore in principle explain how FGFs play several distinct roles in other developing tissues and developmental stages. Copyright © 2017 the authors 0270-6474/17/375690-09$15.00/0.

Inhibition of master transcription factors in pluripotent cells induces early stage differentiation

PubMed Central

De, Debojyoti; Jeong, Myong-Ho; Leem, Young-Eun; Svergun, Dmitri I.; Wemmer, David E.; Kang, Jong-Sun; Kim, Kyeong Kyu; Kim, Sung-Hou

2014-01-01

The potential for pluripotent cells to differentiate into diverse specialized cell types has given much hope to the field of regenerative medicine. Nevertheless, the low efficiency of cell commitment has been a major bottleneck in this field. Here we provide a strategy to enhance the efficiency of early differentiation of pluripotent cells. We hypothesized that the initial phase of differentiation can be enhanced if the transcriptional activity of master regulators of stemness is suppressed, blocking the formation of functional transcriptomes. However, an obstacle is the lack of an efficient strategy to block protein–protein interactions. In this work, we take advantage of the biochemical property of seventeen kilodalton protein (Skp), a bacterial molecular chaperone that binds directly to sex determining region Y-box 2 (Sox2). The small angle X-ray scattering analyses provided a low resolution model of the complex and suggested that the transactivation domain of Sox2 is probably wrapped in a cleft on Skp trimer. Upon the transduction of Skp into pluripotent cells, the transcriptional activity of Sox2 was inhibited and the expression of Sox2 and octamer-binding transcription factor 4 was reduced, which resulted in the expression of early differentiation markers and appearance of early neuronal and cardiac progenitors. These results suggest that the initial stage of differentiation can be accelerated by inhibiting master transcription factors of stemness. This strategy can possibly be applied to increase the efficiency of stem cell differentiation into various cell types and also provides a clue to understanding the mechanism of early differentiation. PMID:24434556

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

Profiling of differentially expressed genes critical to storage root development in hydroponically and in-vitro grown sweetpotato for space farming

NASA Astrophysics Data System (ADS)

Egnin, M.; Gao, H.; He, G.; Woullard, F.; Mortley, D.; Scoffield, J.; Bey, B.; Quain, M.; Prakash, C. S.; Bonsi, C.

Environment is known to have significant effects on the nutrient content and quality of crop plants especially through its impact on the temporal and spatial expression of genes Little is known about the molecular changes and harvest index in plants in response to microgravity Sweetpotato underline Ipomoea underline batatas L Lam is one of the most important root crops and an excellent NASA crop for space farming to provide essential nutrients to sustain human life on long-term space missions The initiation and development of storage root formation is one of the most critical processes determining yield of sweetpotato The molecular mechanism of storage root initiation and development in sweetpotato is poorly understood To this end knowledge of gravity perception the genetic and molecular nature of the induction process of storage root will tremendously help improve on sweetpotato harvest index for space farming cDNA-AFLP techniques were employed to investigate temporal and spatial expressions to gain molecular insights and identify transcripts differentially expressed during early stages of sweetpotato storage root development Two hydroponically grown cultivars using Nutrient Film Technology NFT and microstorage roots were evaluated TU-82-155 an early maturing 90 DAP with orange flesh and tinge red skin and PI318846-3 a late maturing 135 DAP with white flesh and off-yellow skin were compared for differential genes expression during storage root development at 14 21 28 35 and 45 DAP Total RNA was isolated from

454 Transcriptome sequencing suggests a role for two-component signalling in cellularization and differentiation of barley endosperm transfer cells.

PubMed

Thiel, Johannes; Hollmann, Julien; Rutten, Twan; Weber, Hans; Scholz, Uwe; Weschke, Winfriede

2012-01-01

Cell specification and differentiation in the endosperm of cereals starts at the maternal-filial boundary and generates the endosperm transfer cells (ETCs). Besides the importance in assimilate transfer, ETCs are proposed to play an essential role in the regulation of endosperm differentiation by affecting development of proximate endosperm tissues. We attempted to identify signalling elements involved in early endosperm differentiation by using a combination of laser-assisted microdissection and 454 transcriptome sequencing. 454 sequencing of the differentiating ETC region from the syncytial state until functionality in transfer processes captured a high proportion of novel transcripts which are not available in existing barley EST databases. Intriguingly, the ETC-transcriptome showed a high abundance of elements of the two-component signalling (TCS) system suggesting an outstanding role in ETC differentiation. All components and subfamilies of the TCS, including distinct kinds of membrane-bound receptors, have been identified to be expressed in ETCs. The TCS system represents an ancient signal transduction system firstly discovered in bacteria and has previously been shown to be co-opted by eukaryotes, like fungi and plants, whereas in animals and humans this signalling route does not exist. Transcript profiling of TCS elements by qRT-PCR suggested pivotal roles for specific phosphorelays activated in a coordinated time flow during ETC cellularization and differentiation. ETC-specificity of transcriptionally activated TCS phosphorelays was assessed for early differentiation and cellularization contrasting to an extension of expression to other grain tissues at the beginning of ETC maturation. Features of candidate genes of distinct phosphorelays and transcriptional activation of genes putatively implicated in hormone signalling pathways hint at a crosstalk of hormonal influences, putatively ABA and ethylene, and TCS signalling. Our findings suggest an integral function for the TCS in ETC differentiation possibly coupled to sequent hormonal regulation by ABA and ethylene.

454 Transcriptome Sequencing Suggests a Role for Two-Component Signalling in Cellularization and Differentiation of Barley Endosperm Transfer Cells

PubMed Central

Thiel, Johannes; Hollmann, Julien; Rutten, Twan; Weber, Hans; Scholz, Uwe; Weschke, Winfriede

2012-01-01

Background Cell specification and differentiation in the endosperm of cereals starts at the maternal-filial boundary and generates the endosperm transfer cells (ETCs). Besides the importance in assimilate transfer, ETCs are proposed to play an essential role in the regulation of endosperm differentiation by affecting development of proximate endosperm tissues. We attempted to identify signalling elements involved in early endosperm differentiation by using a combination of laser-assisted microdissection and 454 transcriptome sequencing. Principal Findings 454 sequencing of the differentiating ETC region from the syncytial state until functionality in transfer processes captured a high proportion of novel transcripts which are not available in existing barley EST databases. Intriguingly, the ETC-transcriptome showed a high abundance of elements of the two-component signalling (TCS) system suggesting an outstanding role in ETC differentiation. All components and subfamilies of the TCS, including distinct kinds of membrane-bound receptors, have been identified to be expressed in ETCs. The TCS system represents an ancient signal transduction system firstly discovered in bacteria and has previously been shown to be co-opted by eukaryotes, like fungi and plants, whereas in animals and humans this signalling route does not exist. Transcript profiling of TCS elements by qRT-PCR suggested pivotal roles for specific phosphorelays activated in a coordinated time flow during ETC cellularization and differentiation. ETC-specificity of transcriptionally activated TCS phosphorelays was assessed for early differentiation and cellularization contrasting to an extension of expression to other grain tissues at the beginning of ETC maturation. Features of candidate genes of distinct phosphorelays and transcriptional activation of genes putatively implicated in hormone signalling pathways hint at a crosstalk of hormonal influences, putatively ABA and ethylene, and TCS signalling. Significance Our findings suggest an integral function for the TCS in ETC differentiation possibly coupled to sequent hormonal regulation by ABA and ethylene. PMID:22848641

The multiple subfunctions of attention: differential developmental gateways to literacy and numeracy.

PubMed

Steele, Ann; Karmiloff-Smith, Annette; Cornish, Kim; Scerif, Gaia

2012-11-01

Attention is construed as multicomponential, but the roles of its distinct subfunctions in shaping the broader developing cognitive landscape are poorly understood. The current study assessed 3- to 6-year-olds (N=83) to: (a) trace developmental trajectories of attentional processes and their structure in early childhood and (b) measure the impact of distinct attention subfunctions on concurrent and longitudinal abilities related to literacy and numeracy. Distinct trajectories across attention measures revealed the emergence of 2 attentional factors, encompassing "executive" and "sustained-selective" processes. Executive attention predicted concurrent abilities across domains at Time 1, whereas sustained-selective attention predicted basic numeracy 1 year later. These concurrent and longitudinal constraints cast a broader light on the unfolding relations between domain-general and domain-specific processes over early childhood. © 2012 The Authors. Child Development © 2012 Society for Research in Child Development, Inc.

Mesenchymal stem cell-derived exosomes have altered microRNA profiles and induce osteogenic differentiation depending on the stage of differentiation

PubMed Central

Wang, Xiaoqin; Omar, Omar; Vazirisani, Forugh; Thomsen, Peter

2018-01-01

Human mesenchymal stem cell (hMSC)-derived exosomes have shown regenerative effects, but their role in osteogenesis and the underlying mechanism are yet to be determined. In this study, we examined the time-course secretion of exosomes by hMSCs during the entire process of osteogenic differentiation. Exosomes derived from hMSCs in various stages of osteogenic differentiation committed homotypic cells to differentiate towards osteogenic lineage, but only exosomes from late stages of osteogenic differentiation induced extracellular matrix mineralisation. Exosomes from expansion and early and late stages of osteogenic differentiation were internalised by a subpopulation of hMSCs. MicroRNA profiling revealed a set of differentially expressed exosomal microRNAs from the late stage of osteogenic differentiation, which were osteogenesis related. Target prediction demonstrated that these microRNAs enriched pathways involved in regulation of osteogenic differentiation and general mechanisms how exosomes exert their functions, such as “Wnt signalling pathway” and “endocytosis”. Taken together, the results show that MSCs secrete exosomes with different biological properties depending on differentiation stage of their parent cells. The exosomal cargo transferred from MSCs in the late stage of differentiation induces osteogenic differentiation and mineralisation. Moreover, it is suggested that the regulatory effect on osteogenesis by exosomes is at least partly exerted by exosomal microRNA. PMID:29447276

Making lineage decisions with biological noise: Lessons from the early mouse embryo.

PubMed

Simon, Claire S; Hadjantonakis, Anna-Katerina; Schröter, Christian

2018-04-30

Understanding how individual cells make fate decisions that lead to the faithful formation and homeostatic maintenance of tissues is a fundamental goal of contemporary developmental and stem cell biology. Seemingly uniform populations of stem cells and multipotent progenitors display a surprising degree of heterogeneity, primarily originating from the inherent stochastic nature of molecular processes underlying gene expression. Despite this heterogeneity, lineage decisions result in tissues of a defined size and with consistent proportions of differentiated cell types. Using the early mouse embryo as a model we review recent developments that have allowed the quantification of molecular intercellular heterogeneity during cell differentiation. We first discuss the relationship between these heterogeneities and developmental cellular potential. We then review recent theoretical approaches that formalize the mechanisms underlying fate decisions in the inner cell mass of the blastocyst stage embryo. These models build on our extensive knowledge of the genetic control of fate decisions in this system and will become essential tools for a rigorous understanding of the connection between noisy molecular processes and reproducible outcomes at the multicellular level. We conclude by suggesting that cell-to-cell communication provides a mechanism to exploit and buffer intercellular variability in a self-organized process that culminates in the reproducible formation of the mature mammalian blastocyst stage embryo that is ready for implantation into the maternal uterus. This article is categorized under: Gene Expression and Transcriptional Hierarchies > Cellular Differentiation Establishment of Spatial and Temporal Patterns > Regulation of Size, Proportion, and Timing Gene Expression and Transcriptional Hierarchies > Gene Networks and Genomics Gene Expression and Transcriptional Hierarchies > Quantitative Methods and Models. © 2018 Wiley Periodicals, Inc.

High content analysis of differentiation and cell death in human adipocytes.

PubMed

Doan-Xuan, Quang Minh; Sarvari, Anitta K; Fischer-Posovszky, Pamela; Wabitsch, Martin; Balajthy, Zoltan; Fesus, Laszlo; Bacso, Zsolt

2013-10-01

Understanding adipocyte biology and its homeostasis is in the focus of current obesity research. We aimed to introduce a high-content analysis procedure for directly visualizing and quantifying adipogenesis and adipoapoptosis by laser scanning cytometry (LSC) in a large population of cell. Slide-based image cytometry and image processing algorithms were used and optimized for high-throughput analysis of differentiating cells and apoptotic processes in cell culture at high confluence. Both preadipocytes and adipocytes were simultaneously scrutinized for lipid accumulation, texture properties, nuclear condensation, and DNA fragmentation. Adipocyte commitment was found after incubation in adipogenic medium for 3 days identified by lipid droplet formation and increased light absorption, while terminal differentiation of adipocytes occurred throughout day 9-14 with characteristic nuclear shrinkage, eccentric nuclei localization, chromatin condensation, and massive lipid deposition. Preadipocytes were shown to be more prone to tumor necrosis factor alpha (TNFα)-induced apoptosis compared to mature adipocytes. Importantly, spontaneous DNA fragmentation was observed at early stage when adipocyte commitment occurs. This DNA damage was independent from either spontaneous or induced apoptosis and probably was part of the differentiation program. © 2013 International Society for Advancement of Cytometry. Copyright © 2013 International Society for Advancement of Cytometry.

LIF inhibits osteoblast differentiation at least in part by regulation of HAS2 and its product hyaluronan.

PubMed

Falconi, Dominic; Aubin, Jane E

2007-08-01

LIF arrests osteogenesis in fetal rat calvaria cells in a differentiation stage-specific manner. Differential display identified HAS2 as a LIF-induced gene and its product, HA, modulated osteoblast differentiation similarly to LIF. Our data suggest that LIF arrests osteoblast differentiation by altering HA content of the extracellular matrix. Leukemia inhibitory factor (LIF) elicits both anabolic and catabolic effects on bone. We previously showed in the fetal rat calvaria (RC) cell system that LIF inhibits osteoblast differentiation at the late osteoprogenitor/early osteoblast stage. To uncover potential molecular mediators of this inhibitory activity, we used a positive-negative genome-wide differential display screen to identify LIF-induced changes in the developing osteoblast transcriptome. Although LIF signaling is active throughout the RC cell proliferation-differentiation sequence, only a relatively small number of genes, in several different functional clusters, are modulated by LIF specifically during the LIF-sensitive inhibitory time window. Based on their known and predicted functions, most of the LIF-regulated genes identified are plausible candidates to be involved in the LIF-induced arrest of osteoprogenitor differentiation. To test this hypothesis, we further analyzed the function of one of the genes identified, hyaluronan synthase 2 (HAS2), in the LIF-induced inhibition. Synthesis of hyaluronan (HA), the product of HAS enzymatic activity, was stimulated by LIF and mimicked the HAS2 expression profile, with highest expression in early/proliferative and late/maturing cultures and lowest levels in intermediate/late osteoprogenitor-early osteoblast cultures. Exogenously added high molecular weight HA, the product of HAS2, dose-dependently inhibited osteoblast differentiation, with pulse-treatment effective in the same differentiation stage-specific inhibitory window as seen with LIF. In addition, however, pulse treatment with HA in early cultures slightly increased bone nodule formation. Treatment with hyaluronidase, on the other hand, stimulated bone nodule formation in early cultures but caused a small dose-dependent inhibition of osteoblast differentiation in the LIF- and HA-sensitive late time window. Together the data suggest that osteoblast differentiation is acutely sensitive to HA levels and that LIF inhibits osteoblast development at least in part by stimulating high molecular weight HA synthesis through HAS2.

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

PubMed

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

2012-05-01

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

Sp100 colocalizes with HPV replication foci and restricts the productive stage of the infectious cycle

PubMed Central

Khurana, Simran; Warburton, Alix

2017-01-01

We have shown previously that Sp100 (a component of the ND10 nuclear body) represses transcription, replication and establishment of incoming human papillomavirus (HPV) DNA in the early stages of infection. In this follow up study, we show that Sp100 does not substantially regulate viral infection in the maintenance phase, however at late stages of infection Sp100 interacts with amplifying viral genomes to repress viral processes. We find that Sp100 localizes to HPV16 replication foci generated in primary keratinocytes, to HPV31 replication foci that form in differentiated cells, and to HPV16 replication foci in CIN 1 cervical biopsies. To analyze this further, Sp100 was down regulated by siRNA treatment of differentiating HPV31 containing cells and levels of viral transcription and replication were assessed. This revealed that Sp100 represses viral transcription and replication in differentiated cells. Analysis of Sp100 binding to viral chromatin showed that Sp100 bound across the viral genome, and that binding increased at late stages of infection. Therefore, Sp100 represses the HPV life cycle at both early and late stages of infection. PMID:28968443

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

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

Exploring the Largest Mass Fraction of the Solar System: the Case for Planetary Interiors

NASA Technical Reports Server (NTRS)

Danielson, L. R.; Draper, D.; Righter, K.; McCubbin, F.; Boyce, J.

2017-01-01

Why explore planetary interiors: The typical image that comes to mind for planetary science is that of a planet surface. And while surface data drive our exploration of evolved geologic processes, it is the interiors of planets that hold the key to planetary origins via accretionary and early differentiation processes. It is that initial setting of the bulk planet composition that sets the stage for all geologic processes that follow. But nearly all of the mass of planets is inaccessible to direct examination, making experimentation an absolute necessity for full planetary exploration.

Deformation of a crystalline olivine aggregate containing two immiscible liquids: Implications for early core-mantle differentiation

NASA Astrophysics Data System (ADS)

Cerantola, V.; Walte, N. P.; Rubie, D. C.

2015-05-01

Deformation-assisted segregation of metallic and sulphidic liquid from a solid peridotitic matrix is a process that may contribute to the early differentiation of small planetesimals into a metallic core and a silicate mantle. Here we present results of an experimental study using a simplified system consisting of a polycrystalline Fo90-olivine matrix containing a small percentage of iron sulphide and a synthetic primitive MORB melt, in order to investigate whether the silicate melt enhances the interconnection and segregation of FeS liquid under deformation conditions at varying strain rates. The experiments have been performed at 2 GPa, 1450 °C and strain rates between 1 ×10-3s-1 to 1 ×10-5s-1. Our results show that the presence of silicate melt actually hinders the migration and segregation of sulphide liquid by reducing its interconnectivity. At low to moderate strain rates the sulphide liquid pockets preserved a roundish shape, showing the liquid behavior is governed mainly by surface tension rather than by differential stress. Even at the highest strain rates, insignificant FeS segregation and interconnection were observed. On the other hand the basaltic melt was very mobile during deformation, accommodating part of the strain, which led to its segregation from the matrix at high bulk strains leaving the sulphide liquid stranded in the olivine matrix. Hence, we conclude that deformation-induced percolation of sulphide liquid does not contribute to the formation of planetary cores after the silicate solidus is overstepped. A possible early deformation enhanced core-mantle differentiation after overstepping the Fe-S solidus is not possible between the initial formation of silicate melt and the formation of a widespread magma ocean.

Induction of Oligodendrocyte Differentiation and In Vitro Myelination by Inhibition of Rho-Associated Kinase

PubMed Central

Taylor, Christopher; Pereira, Albertina; Seng, Michelle; Tham, Chui-Se; Izrael, Michal; Webb, Michael

2014-01-01

In inflammatory demyelinating diseases such as multiple sclerosis (MS), myelin degradation results in loss of axonal function and eventual axonal degeneration. Differentiation of resident oligodendrocyte precursor cells (OPCs) leading to remyelination of denuded axons occurs regularly in early stages of MS but halts as the pathology transitions into progressive MS. Pharmacological potentiation of endogenous OPC maturation and remyelination is now recognized as a promising therapeutic approach for MS. In this study, we analyzed the effects of modulating the Rho-A/Rho-associated kinase (ROCK) signaling pathway, by the use of selective inhibitors of ROCK, on the transformation of OPCs into mature, myelinating oligodendrocytes. Here we demonstrate, with the use of cellular cultures from rodent and human origin, that ROCK inhibition in OPCs results in a significant generation of branches and cell processes in early differentiation stages, followed by accelerated production of myelin protein as an indication of advanced maturation. Furthermore, inhibition of ROCK enhanced myelin formation in cocultures of human OPCs and neurons and remyelination in rat cerebellar tissue explants previously demyelinated with lysolecithin. Our findings indicate that by direct inhibition of this signaling molecule, the OPC differentiation program is activated resulting in morphological and functional cell maturation, myelin formation, and regeneration. Altogether, we show evidence of modulation of the Rho-A/ROCK signaling pathway as a viable target for the induction of remyelination in demyelinating pathologies. PMID:25289646

WNTLESS IS REQUIRED FOR PERIPHERAL LUNG DIFFERENTIATION AND PULMONARY VASCULAR DEVELOPMENT

PubMed Central

Cornett, Bridget; Snowball, John; Varisco, Brian M.; Lang, Richard; Whitsett, Jeffrey; Sinner, Debora

2013-01-01

Wntless (Wls), a gene highly conserved across the animal kingdom, encodes for a transmembrane protein that mediates Wnt ligand secretion. Wls is expressed in developing lung, wherein Wnt signaling is necessary for pulmonary morphogenesis. We hypothesize that Wls plays a critical role in modulating Wnt signaling during lung development and therefore affects processes critical for pulmonary morphogenesis. We generated conditional Wls mutant mice utilizing Shh-Cre and Dermo1-Cre mice to delete Wls in the embryonic respiratory epithelium and mesenchyme, respectively. Epithelial deletion of Wls disrupted lung branching morphogenesis, peripheral lung development and pulmonary endothelial differentiation. Epithelial Wls mutant mice died at birth due to respiratory failure caused by lung hypoplasia and pulmonary hemorrhage. In the lungs of these mice, VEGF and Tie2-angiopoietin signaling pathways, which mediate vascular development, were downregulated from early stages of development. In contrast, deletion of Wls in mesenchymal cells of the developing lung did not alter branching morphogenesis or early mesenchymal differentiation. In vitro assays support the concept that Wls acts in part via Wnt5a to regulate pulmonary vascular development. We conclude that epithelial Wls modulates Wnt ligand activities critical for pulmonary vascular differentiation and peripheral lung morphogenesis. These studies provide a new framework for understanding the molecular mechanisms underlying normal pulmonary vasculature formation and the dysmorphic pulmonary vasculature development associated with congenital lung disease. PMID:23523683

Wntless is required for peripheral lung differentiation and pulmonary vascular development.

PubMed

Cornett, Bridget; Snowball, John; Varisco, Brian M; Lang, Richard; Whitsett, Jeffrey; Sinner, Debora

2013-07-01

Wntless (Wls), a gene highly conserved across the animal kingdom, encodes for a transmembrane protein that mediates Wnt ligand secretion. Wls is expressed in developing lung, wherein Wnt signaling is necessary for pulmonary morphogenesis. We hypothesize that Wls plays a critical role in modulating Wnt signaling during lung development and therefore affects processes critical for pulmonary morphogenesis. We generated conditional Wls mutant mice utilizing Shh-Cre and Dermo1-Cre mice to delete Wls in the embryonic respiratory epithelium and mesenchyme, respectively. Epithelial deletion of Wls disrupted lung branching morphogenesis, peripheral lung development and pulmonary endothelial differentiation. Epithelial Wls mutant mice died at birth due to respiratory failure caused by lung hypoplasia and pulmonary hemorrhage. In the lungs of these mice, VEGF and Tie2-angiopoietin signaling pathways, which mediate vascular development, were downregulated from early stages of development. In contrast, deletion of Wls in mesenchymal cells of the developing lung did not alter branching morphogenesis or early mesenchymal differentiation. In vitro assays support the concept that Wls acts in part via Wnt5a to regulate pulmonary vascular development. We conclude that epithelial Wls modulates Wnt ligand activities critical for pulmonary vascular differentiation and peripheral lung morphogenesis. These studies provide a new framework for understanding the molecular mechanisms underlying normal pulmonary vasculature formation and the dysmorphic pulmonary vasculature development associated with congenital lung disease. Copyright © 2013 Elsevier Inc. All rights reserved.

[Effect of human oviductal embryotrophic factors on gene expression of mouse preimplantation embryos].

PubMed

Yao, Yuan-Qing; Lee, Kai-Fai; Xu, Jia-Seng; Ho, Pak-Chung; Yeung, Shu-Biu

2007-09-01

To investigate the effect of embryotrophic factors (ETF) from human oviductal cells on gene expression of mouse early developmental embryos and discuss the role of fallopian tube in early development of embryos. ETF was isolated from conditioned medium of human oviductal cell line by sequential liquid chromatographic systems. Mouse embryos were treated by ETF in vitro. Using differential display RT-PCR, the gene expression of embryos treated by ETF was compared with embryos without ETF treatment. The differentially expressed genes were separated, re-amplified, cloned and sequenced. Gene expression profiles of embryos with ETF treatment was different from embryos without this treatment. Eight differentially expressed genes were cloned and sequenced. These genes functioned in RNA degradation, synthesis, splicing, protein trafficking, cellular differentiation and embryo development. Embryotrophic factors from human oviductal cells affect gene expression of early developmental embryos. The human oviductal cells play wide roles in early developmental stages of embryos.

In vivo differentiation of human periodontal ligament cells leads to formation of dental hard tissue.

PubMed

Wolf, M; Lossdörfer, S; Abuduwali, N; Meyer, R; Kebir, S; Götz, W; Jäger, A

2013-11-01

Following trauma, periodontal disease, or orthodontic tooth movement, residual periodontal ligament (PDL) cells at the defect site are considered mandatory for successful regeneration of the injured structures. Recent developments in tissue engineering focus, as one pillar, on the transplantation of PDL cells to support periodontal regeneration processes. Here, we examined the ability of osteogenically predifferentiated PDL cells to undergo further osteoblastic or cementoblastic differentiation and to mineralize their extracellular matrix when transplanted in an in vivo microenvironment. Using collagen sponges as carriers, osteogenically predifferentiated human PDL cells were transplanted subcutaneously into six immunocompromised CD-1® nude mice. Following explantation after 28 days, osteogenic and cementogenic marker protein expression was visualized immunohistochemically. After 28 days, transplanted PDL cells revealed both cellular, cytoplasmatic and extracellular immunoreactivity for the chosen markers alkaline phosphatase, osteopontin, PTH-receptor 1, and osteocalcin. Specific osteogenic and cementoblastic differentiation was demonstrated by RUNX2 and CEMP1 immunoreactivity. Early stages of mineralization were demonstrated by calcium and phosphate staining. Our results reinforce the previously published reports of PDL cell mineralization in vivo and further demonstrate the successful induction of specific osteogenic and cementogenic differentiation of transplanted human PDL cells in vivo. These findings reveal promising possibilities for supporting periodontal remodeling and regeneration processes with PDL cells being potential target cells with which to influence the process of orthodontically induced root resorption.

Early embryonic expression of FGF4/6/9 gene and its role in the induction of mesenchyme and notochord in Ciona savignyi embryos.

PubMed

Imai, Kaoru S; Satoh, Nori; Satou, Yutaka

2002-04-01

In early Ciona savignyi embryos, nuclear localization of beta-catenin is the first step of endodermal cell specification, and triggers the activation of various target genes. A cDNA for Cs-FGF4/6/9, a gene activated downstream of beta-catenin signaling, was isolated and shown to encode an FGF protein with features of both FGF4/6 and FGF9/20. The early embryonic expression of Cs-FGF4/6/9 was transient and the transcript was seen in endodermal cells at the 16- and 32-cell stages, in notochord and muscle cells at the 64-cell stage, and in nerve cord and muscle cells at the 110-cell stage; the gene was then expressed again in cells of the nervous system after neurulation. When the gene function was suppressed with a specific antisense morpholino oligo, the differentiation of mesenchyme cells was completely blocked, and the fate of presumptive mesenchyme cells appeared to change into that of muscle cells. The inhibition of mesenchyme differentiation was abrogated by coinjection of the morpholino oligo and synthetic Cs-FGF4/6/9 mRNA. Downregulation of beta-catenin nuclear localization resulted in the absence of mesenchyme cell differentiation due to failure of the formation of signal-producing endodermal cells. Injection of synthetic Cs-FGF4/6/9 mRNA in beta-catenin-downregulated embryos evoked mesenchyme cell differentiation. These results strongly suggest that Cs-FGF4/6/9 produced by endodermal cells acts an inductive signal for the differentiation of mesenchyme cells. On the other hand, the role of Cs-FGF4/6/9 in the induction of notochord cells is partial; the initial process of the induction was inhibited by Cs-FGF4/6/9 morpholino oligo, but notochord-specific genes were expressed later to form a partial notochord.

Differentiation induction of mouse embryonic stem cells into sinus node-like cells by suramin

PubMed Central

Wiese, Cornelia; Nikolova, Teodora; Zahanich, Ihor; Sulzbacher, Sabine; Fuchs, Joerg; Yamanaka, Satoshi; Graf, Eva; Ravens, Ursula; Boheler, Kenneth R.; Wobus, Anna M.

2015-01-01

Background Embryonic stem (ES) cells differentiate into cardiac phenotypes representing early pacemaker-, atrial-, ventricular-, and sinus node-like cells, however, ES-derived specification into sinus nodal cells is not yet known. By using the naphthylamine derivative of urea, suramin, we were able to follow the process of cardiac specialization into sinus node-like cells. Methods Differentiating mouse ES cells were treated with suramin (500 μM) from day 5 to 7 of embryoid body formation, and cells were analysed for their differentiation potential via morphological analysis, flow cytometry, RT-PCR, immunohistochemistry and patch clamp analysis. Results Application of suramin resulted in an increased number of cardiac cells, but inhibition of neuronal, skeletal muscle and definitive endoderm differentiation. Immediately after suramin treatment, a decreased mesendoderm differentiation was found. Brachyury, FGF10, Wnt8 and Wnt3a transcript levels were significantly down-regulated, followed by a decrease in mesoderm- and cardiac progenitor-specific markers BMP2, GATA4/5, Wnt11, Isl1, Nkx2.5 and Tbx5 immediately after removal of the substance. With continued differentiation, a significant up-regulation of Brachyury, FGF10 and GATA5 transcript levels was observed, whereas Nkx2.5, Isl1, Tbx5, BMP2 and Wnt11 levels were normalized to control levels. At advanced differentiation stages, sinus node-specific HCN4, Tbx2 and Tbx3 transcript levels were significantly up-regulated. Immunofluorescence and patch-clamp analysis confirmed the increased number of sinus node-like cells, and electrophysiological analysis revealed a lower number of atrial- and ventricular-like cardiomyocytes following suramin treatment. Conclusion We conclude that the interference of suramin with the cardiac differentiation process modified mesoderm- and cardiac-specific gene expression resulting in enhanced formation of sinus node-like cells. PMID:19775764

Dictyostelium cell death: early emergence and demise of highly polarized paddle cells.

PubMed

Levraud, Jean-Pierre; Adam, Myriam; Luciani, Marie-Françoise; de Chastellier, Chantal; Blanton, Richard L; Golstein, Pierre

2003-03-31

Cell death in the stalk of Dictyostelium discoideum, a prototypic vacuolar cell death, can be studied in vitro using cells differentiating as a monolayer. To identify early events, we examined potentially dying cells at a time when the classical signs of Dictyostelium cell death, such as heavy vacuolization and membrane lesions, were not yet apparent. We observed that most cells proceeded through a stereotyped series of differentiation stages, including the emergence of "paddle" cells showing high motility and strikingly marked subcellular compartmentalization with actin segregation. Paddle cell emergence and subsequent demise with paddle-to-round cell transition may be critical to the cell death process, as they were contemporary with irreversibility assessed through time-lapse videos and clonogenicity tests. Paddle cell demise was not related to formation of the cellulose shell because cells where the cellulose-synthase gene had been inactivated underwent death indistinguishable from that of parental cells. A major subcellular alteration at the paddle-to-round cell transition was the disappearance of F-actin. The Dictyostelium vacuolar cell death pathway thus does not require cellulose synthesis and includes early actin rearrangements (F-actin segregation, then depolymerization), contemporary with irreversibility, corresponding to the emergence and demise of highly polarized paddle cells.

A Nonmagnetic Differentiated Early Planetary Body

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

Weiss, Benjamin P.; Wang, Jun

2017-06-15

Paleomagnetic studies of meteorites have shown that the solar nebula was likely magnetized and that many early planetary bodies generated dynamo magnetic fields in their advecting metallic cores. The surface fields on these bodies were recorded by a diversity of chondrites and achondrites, ranging in intensity from several μT to several hundred μT. In fact, an achondrite parent body without evidence for paleomagnetic fields has yet to be confidently identified, hinting that early solar system field generation and the dynamo process in particular may have been common. Here we present paleomagnetic measurements of the ungrouped achondrite NWA 7325 indicating thatmore » it last cooled in a near-zero field (<∼1.7μT), estimated to have occurred at 4563.09 ± 0.26 million years ago (Ma) from Al–Mg chronometry. Because NWA 7325 is highly depleted in siderophile elements, its parent body nevertheless underwent large-scale metal-silicate differentiation and likely formed a metallic core. This makes NWA 7325 the first recognized example of an essentially unmagnetized igneous rock from a differentiated early solar system body. These results indicate that all magnetic fields, including those from any core dynamo on the NWA 7325 parent body, the solar nebula, young Sun, and solar wind, were <1.7 μT at the location of NWA 7325 at 4563 Ma. This supports a recent conclusion that the solar nebula had dissipated by ∼4 million years after solar system formation. NWA 7325 also serves as an experimental control that gives greater confidence in the positive identification of remanent magnetization in other achondrites.« less

The Cdk4-E2f1 pathway regulates early pancreas development by targeting Pdx1+ progenitors and Ngn3+ endocrine precursors

PubMed Central

Kim, So Yoon; Rane, Sushil G.

2011-01-01

Cell division and cell differentiation are intricately regulated processes vital to organ development. Cyclin-dependent kinases (Cdks) are master regulators of the cell cycle that orchestrate the cell division and differentiation programs. Cdk1 is essential to drive cell division and is required for the first embryonic divisions, whereas Cdks 2, 4 and 6 are dispensable for organogenesis but vital for tissue-specific cell development. Here, we illustrate an important role for Cdk4 in regulating early pancreas development. Pancreatic development involves extensive morphogenesis, proliferation and differentiation of the epithelium to give rise to the distinct cell lineages of the adult pancreas. The cell cycle molecules that specify lineage commitment within the early pancreas are unknown. We show that Cdk4 and its downstream transcription factor E2f1 regulate mouse pancreas development prior to and during the secondary transition. Cdk4 deficiency reduces embryonic pancreas size owing to impaired mesenchyme development and fewer Pdx1+ pancreatic progenitor cells. Expression of activated Cdk4R24C kinase leads to increased Nkx2.2+ and Nkx6.1+ cells and a rise in the number and proliferation of Ngn3+ endocrine precursors, resulting in expansion of the β cell lineage. We show that E2f1 binds and activates the Ngn3 promoter to modulate Ngn3 expression levels in the embryonic pancreas in a Cdk4-dependent manner. These results suggest that Cdk4 promotes β cell development by directing E2f1-mediated activation of Ngn3 and increasing the pool of endocrine precursors, and identify Cdk4 as an important regulator of early pancreas development that modulates the proliferation potential of pancreatic progenitors and endocrine precursors. PMID:21490060

Micro-Topographies Promote Late Chondrogenic Differentiation Markers in the ATDC5 Cell Line.

PubMed

Le, Bach Q; Vasilevich, Aliaksei; Vermeulen, Steven; Hulshof, Frits; Stamatialis, Dimitrios F; van Blitterswijk, Clemens A; de Boer, Jan

2017-05-01

Chemical and mechanical cues are well-established influencers of in vitro chondrogenic differentiation of ATDC5 cells. Here, we investigate the role of topographical cues in this differentiation process, a study not been explored before. Previously, using a library of surface micro-topographies we found some distinct patterns that induced alkaline phosphatase (ALP) production in human mesenchymal stromal cells. ALP is also a marker for hypertrophy, the end stage of chondrogenic differentiation preceding bone formation. Thus, we hypothesized that these patterns could influence end-stage chondrogenic differentiation of ATDC5 cells. In this study, we randomly selected seven topographies among the ALP influencing hits. Cells grown on these surfaces displayed varying nuclear shape and actin filament structure. When stimulated with insulin-transferrin-selenium (ITS) medium, nodule formation occurred and in some cases showed alignment to the topographical patterns. Gene expression analysis of cells growing on topographical surfaces in the presence of ITS medium revealed a downregulation of early markers and upregulation of late markers of chondrogenic differentiation compared to cells grown on a flat surface. In conclusion, we demonstrated that surface topography in addition to other cues can promote hypertrophic differentiation suitable for bone tissue engineering.

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

The multifaceted functions of C/EBPα in normal and malignant haematopoiesis.

PubMed

Ohlsson, E; Schuster, M B; Hasemann, M; Porse, B T

2016-04-01

The process of blood formation, haematopoiesis, depends upon a small number of haematopoietic stem cells (HSCs) that reside in the bone marrow. Differentiation of HSCs is characterised by decreased expression of genes associated with self-renewal accompanied by a stepwise activation of genes promoting differentiation. Lineage branching is further directed by groups of cooperating and counteracting genes forming complex networks of lineage-specific transcription factors. Imbalances in such networks can result in blockage of differentiation, lineage reprogramming and malignant transformation. CCAAT/enhancer-binding protein-α (C/EBPα) was originally identified 30 years ago as a transcription factor that binds both promoter and enhancer regions. Most of the early work focused on the role of C/EBPα in regulating transcriptional processes as well as on its functions in key differentiation processes during liver, adipogenic and haematopoietic development. Specifically, C/EBPα was shown to control differentiation by its ability to coordinate transcriptional output with cell cycle progression. Later, its role as an important tumour suppressor, mainly in acute myeloid leukaemia (AML), was recognised and has been the focus of intense studies by a number of investigators. More recent work has revisited the role of C/EBPα in normal haematopoiesis, especially its function in HSCs, and also started to provide more mechanistic insights into its role in normal and malignant haematopoiesis. In particular, the differential actions of C/EBPα isoforms, as well as its importance in chromatin remodelling and cellular reprogramming, are beginning to be elucidated. Finally, recent work has also shed light on the dichotomous function of C/EBPα in AML by demonstrating its ability to act as both a tumour suppressor and promoter. In the present review, we will summarise the current knowledge on the functions of C/EBPα during normal and malignant haematopoiesis with special emphasis on the recent work.

Developmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin attenuates capacity of hematopoietic stem cells to undergo lymphocyte differentiation

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

Ahrenhoerster, Lori S.; Tate, Everett R.; Lakatos, Peter A.

The process of hematopoiesis, characterized by long-term self-renewal and multi-potent lineage differentiation, has been shown to be regulated in part by the ligand-activated transcription factor known as the aryl hydrocarbon receptor (AHR). 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a ubiquitous contaminant and the most potent AHR agonist, also modulates regulation of adult hematopoietic stem and progenitor cell (HSC/HPC) homeostasis. However, the effect of developmental TCDD exposure on early life hematopoiesis has not been fully explored. Given the inhibitory effects of TCDD on hematopoiesis and lymphocyte development, we hypothesized that in utero exposure to TCDD would alter the functional capacity of fetal HSC/HPCs to completemore » lymphocyte differentiation. To test this hypothesis, we employed a co-culture system designed to facilitate the maturation of progenitor cells to either B or T lymphocytes. Furthermore, we utilized an innovative limiting dilution assay to precisely quantify differences in lymphocyte differentiation between HSC/HPCs obtained from fetuses of dams exposed to 3 μg/kg TCDD or control. We found that the AHR is transcribed in yolk sac hematopoietic cells and is transcriptionally active as early as gestational day (GD) 7.5. Furthermore, the number of HSC/HPCs present in the fetal liver on GD 14.5 was significantly increased in fetuses whose mothers were exposed to TCDD throughout pregnancy. Despite this increase in HSC/HPC cell number, B and T lymphocyte differentiation is decreased by approximately 2.5 fold. These findings demonstrate that inappropriate developmental AHR activation in HSC/HPCs adversely impacts lymphocyte differentiation and may have consequences for lymphocyte development in the bone marrow and thymus later in life.« less

Regulation of germ cell development by intercellular signaling in the mammalian ovarian follicle.

PubMed

Clarke, Hugh J

2018-01-01

Prior to ovulation, the mammalian oocyte undergoes a process of differentiation within the ovarian follicle that confers on it the ability to give rise to an embryo. Differentiation comprises two phases-growth, during which the oocyte increases more than 100-fold in volume as it accumulates macromolecules and organelles that will sustain early embryogenesis; and meiotic maturation, during which the oocyte executes the first meiotic division and prepares for the second division. Entry of an oocyte into the growth phase appears to be triggered when the adjacent granulosa cells produce specific growth factors. As the oocyte grows, it elaborates a thick extracellular coat termed the zona pellucida. Nonetheless, cytoplasmic extensions of the adjacent granulosa cells, termed transzonal projections (TZPs), enable them to maintain contact-dependent communication with the oocyte. Through gap junctions located where the TZP tips meet the oocyte membrane, they provide the oocyte with products that sustain its metabolic activity and signals that regulate its differentiation. Conversely, the oocyte secretes diffusible growth factors that regulate proliferation and differentiation of the granulosa cells. Gap junction-permeable products of the granulosa cells prevent precocious initiation of meiotic maturation, and the gap junctions also enable oocyte maturation to begin in response to hormonal signals received by the granulosa cells. Development of the oocyte or the somatic compartment may also be regulated by extracellular vesicles newly identified in follicular fluid and at TZP tips, which could mediate intercellular transfer of macromolecules. Oocyte differentiation thus depends on continuous signaling interactions with the somatic cells of the follicle. WIREs Dev Biol 2018, 7:e294. doi: 10.1002/wdev.294 This article is categorized under: Gene Expression and Transcriptional Hierarchies > Cellular Differentiation Signaling Pathways > Cell Fate Signaling Early Embryonic Development > Gametogenesis. © 2017 Wiley Periodicals, Inc.

Language experience differentiates prefrontal and subcortical activation of the cognitive control network in novel word learning.

PubMed

Bradley, Kailyn A L; King, Kelly E; Hernandez, Arturo E

2013-02-15

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 2h 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. Copyright © 2012 Elsevier Inc. All rights reserved.

Notch-dependent T-lineage commitment occurs at extrathymic sites following bone marrow transplantation

PubMed Central

Maillard, Ivan; Schwarz, Benjamin A.; Sambandam, Arivazhagan; Fang, Terry; Shestova, Olga; Xu, Lanwei; Bhandoola, Avinash; Pear, Warren S.

2006-01-01

Early T-lineage progenitors (ETPs) arise after colonization of the thymus by multipotent bone marrow progenitors. ETPs likely serve as physiologic progenitors of T-cell development in adult mice, although alternative T-cell differentiation pathways may exist. While we were investigating mechanisms of T-cell reconstitution after bone marrow transplantation (BMT), we found that efficient donor-derived thymopoiesis occurred before the pool of ETPs had been replenished. Simultaneously, T lineage–restricted progenitors were generated at extrathymic sites, both in the spleen and in peripheral lymph nodes, but not in the bone marrow or liver. The generation of these T lineage–committed cells occurred through a Notch-dependent differentiation process. Multipotent bone marrow progenitors efficiently gave rise to extrathymic T lineage–committed cells, whereas common lymphoid progenitors did not. Our data show plasticity of T-lineage commitment sites in the post-BMT environment and indicate that Notch-driven extrathymic Tlineage commitment from multipotent progenitors may contribute to early T-lineage reconstitution after BMT. PMID:16397133

Early cell lineage specification in a marsupial: a case for diverse mechanisms among mammals.

PubMed

Frankenberg, Stephen; Shaw, Geoff; Freyer, Claudia; Pask, Andrew J; Renfree, Marilyn B

2013-03-01

Early cell lineage specification in eutherian mammals results in the formation of a pluripotent inner cell mass (ICM) and trophoblast. By contrast, marsupials have no ICM. Here, we present the first molecular analysis of mechanisms of early cell lineage specification in a marsupial, the tammar wallaby. There was no overt differential localisation of key lineage-specific transcription factors in cleavage and early unilaminar blastocyst stages. Pluriblast cells (equivalent to the ICM) became distinguishable from trophoblast cells by differential expression of POU5F1 and, to a greater extent, POU2, a paralogue of POU5F1. Unlike in the mouse, pluriblast-trophoblast differentiation coincided with a global nuclear-to-cytoplasmic transition of CDX2 localisation. Also unlike in the mouse, Hippo pathway factors YAP and WWTR1 showed mutually distinct localisation patterns that suggest non-redundant roles. NANOG and GATA6 were conserved as markers of epiblast and hypoblast, respectively, but some differences to the mouse were found in their mode of differentiation. Our results suggest that there is considerable evolutionary plasticity in the mechanisms regulating early lineage specification in mammals.

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.

The developmental basis for germline mosaicism in mouse and Drosophila melanogaster.

PubMed

Drost, J B; Lee, W R

1998-01-01

Data involving germline mosaics in Drosophila melanogaster and mouse are reconciled with developmental observations. Mutations that become fixed in the early embryo before separation of soma from the germline may, by the sampling process of development, continue as part of germline and/or differentiate into any somatic tissue. The cuticle of adult D. melanogaster, because of segmental development, can be used to estimate the proportion of mutant nuclei in the early embryo, but most somatic tissues and the germlines of both species continue from samples too small to be representative of the early embryo. Because of the small sample of cells/nuclei that remain in the germline after separation of soma in both species, mosaic germlines have percentages of mutant cells that vary widely, with a mean of 50% and an unusual platykurtic, flat-topped distribution. While the sampling process leads to similar statistical results for both species, their patterns of development are very different. In D. melanogaster the first differentiation is the separation of soma from germline with the germline continuing from a sample of only two to four nuclei, whereas the adult cuticle is a representative sample of cleavage nuclei. The presence of mosaicism in D. melanogaster germline is independent of mosaicism in the eye, head, and thorax. This independence was used to determine that mutations can occur at any of the early embryonic cell divisions and still average 50% mutant germ cells when the germline is mosaic; however, the later the mutation occurs, the higher the proportion of completely nonmutant germlines. In contrast to D. melanogaster, the first differentiation in the mouse does not separate soma from germline but produces the inner cell mass that is representative of the cleavage nuclei. Following formation of the primitive streak, the primordial germ cells develop at the base of the allantois and among a clonally related sample of cells, providing the same statistical distribution in the mouse germlines as in D. melanogaster. The proportion of mutations that are fixed during early embryonic development is greatly underestimated. For example, a DNA lesion in a postmeiotic gamete that becomes fixed as a dominant mutation during early embryonic development of the F1 may produce an individual completely mutant in the germ line and relevant somatic tissue or, alternatively, the F1 germline may be completely mutant but with no relevant somatic tissues for detecting the mutation until the F2. In both cases the mutation would be classified as complete in the F1 and F2, respectively, and not recognized as embryonic in origin. Because germ cells differentiate later in mammalian development, there are more opportunities for correlation between germline and soma in the mammal than Drosophila. However, because the germ cells and any somatic tissue, like blood, are derived from small samples, there may be many individuals that test negative in blood but have germlines that are either mosaic or entirely mutant.

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

Threat perception in mild cognitive impairment and early dementia.

PubMed

Henry, Julie D; Thompson, Claire; Ruffman, Ted; Leslie, Felicity; Withall, Adrienne; Sachdev, Perminder; Brodaty, Henry

2009-09-01

Mild cognitive impairment (MCI) and dementia affect many aspects of emotion processing. Even though the ability to detect threat is a particularly important aspect of emotion processing, no study to date has assessed threat perception in either of these groups. The purpose of the present study was to test whether individuals with MCI (n = 38) and mild dementia (n = 34) have difficulty differentiating between faces and situations normatively judged to be either high or low in threat relative to age-matched controls (n = 34). To achieve this aim, all participants completed 2 danger rating tasks that involved viewing and rating high- and low-danger images. It was also assessed whether threat perception was related to cognitive functioning and emotion recognition. The results indicated that all 3 groups were accurately, and comparably, able to differentiate high from low-danger faces. However, the dementia group had difficulties differentiating high from low-danger situations, which reflected a bias to overattribute the level of threat posed by normatively judged nonthreatening situations. This difficulty was related to more general cognitive decline.

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.

Iron Speciation in Minerals and Melts at High Pressure: Implications for the Redox Evolution of the Early Mantle

NASA Astrophysics Data System (ADS)

Armstrong, K.; Frost, D. J.; McCammon, C. A.; Rubie, D. C.; Boffa Ballaran, T.; Miyajima, N.

2016-12-01

During the differentiation of the early Earth, the silicates of the mantle must have been in equilibrium with core-forming metal iron, as indicated by the depletion of siderophile elements from the mantle. Studies of ancient rocks suggest that by at least 3.9 Ga, the upper mantle was 4-5 log units more oxidized than metal saturation implies (Delano 2001). The process(es) by which the mantle was oxidized is unclear, but has implications for the timing of accretion, differentiation, and volatile delivery to the early Earth, as well as evolution of the early atmosphere. One plausible oxidation mechanism is suggested by the tendency of high-pressure silicate minerals to favor Fe3+ over Fe2+ in their structures, even at metal saturation. This preference in the lower mantle mineral bridgmanite has been proposed to drive the disproportionation reaction of FeO to form Fe­2O3 and iron metal (Frost and McCammon 2008). We have performed experiments at the Ru-RuO2 fO2 buffer which show that silicate melts may mirror this behavior and Fe3+ may be stabilized with pressure for a constant fO2; by 21 GPa, the previously observed trend of Fe3+ decreasing with pressure (O'Neill, 2006) reverses and ferric iron content had increased. If this is also the case at lower oxygen fugacities, FeO disproportionation may have occurred at the base of an early magma ocean, establishing a redox gradient similar to what is presumed for the mantle today. Here we report results of further multianvil and diamond anvil cell experiments exploring the plausibility of FeO disproportionation driving mantle oxidation. Experiments investigating Fe speciation in high pressure melts at variable fO2 will be discussed along with results of diamond anvil cell experiments investigating ferric iron content of lower mantle minerals at metal saturation.

Differentiation of Induced Pluripotent Stem Cells to Neural Retinal Precursor Cells on Porous Poly-Lactic-co-Glycolic Acid Scaffolds

PubMed Central

Worthington, Kristan S.; Wiley, Luke A.; Guymon, C. Allan; Salem, Aliasger K.

2016-01-01

Abstract Purpose: Cell replacement therapy for the treatment of retinal degeneration is an increasingly feasible approach, but one that still requires optimization of the transplantation strategy. To this end, various polymer substrates can increase cell survival and integration, although the effect of their pore size on cell behavior, particularly differentiation, has yet to be explored. Methods: Salt crystals of varying known size were used to impart structure to poly(lactic-co-glycolic acid) (PLGA) scaffolds by a salt leaching/solvent evaporation process. Mouse induced pluripotent stem cells (miPSCs) were seeded to the polymer scaffolds and supplemented with retinal differentiation media for up to 2 weeks. Proliferation was measured during the course of 2 weeks, while differentiation was evaluated using cell morphology and expression of early retinal development markers. Results: The salt leaching method of porous PLGA fabrication resulted in amorphous smooth pores. Cells attached to these scaffolds and proliferated, reaching a maximum cell number at 10 days postseeding that was 5 times higher on porous PLGA than on nonporous controls. The morphology of many of these cells, including their formation of neurites, was suggestive of neural phenotypes, while their expression of Sox2, Pax6, and Otx2 indicates early retinal development. Conclusions: The use of porous PLGA scaffolds to differentiate iPSCs to retinal phenotypes is a feasible pretransplantation approach. This adds to an important knowledge base; understanding how developing retinal cells interact with polymer substrates with varying structure is a crucial component of optimizing cell therapy strategies. PMID:26692377

Analysis of MYB oncogene in transformed adenoid cystic carcinomas reveals distinct pathways of tumor progression.

PubMed

Costa, Ana F; Altemani, Albina; García-Inclán, Cristina; Fresno, Florentino; Suárez, Carlos; Llorente, José L; Hermsen, Mario

2014-06-01

Adenoid cystic carcinomas can occasionally undergo dedifferentiation, a phenomenon also referred to as high-grade transformation. However, cases of adenoid cystic carcinomas have been described showing transformation to adenocarcinomas that are not poorly differentiated, indicating that high-grade transformation may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form, which may encompass a wide spectrum of carcinomas in terms of aggressiveness. The aim of this study was to gain more insight in the biology of this pathological phenomenon by means of genetic profiling of both histological components. Using microarray comparative genomic hybridization, we compared the genome-wide DNA copy-number changes of the conventional and transformed area of eight adenoid cystic carcinomas with high-grade transformation, comprising four with transformation into moderately differentiated adenocarcinomas and four into poorly differentiated carcinomas. In general, the poorly differentiated carcinoma cases showed a higher total number of copy-number changes than the moderately differentiated adenocarcinoma cases, and this correlated with a worse clinical course. Special attention was given to chromosomal translocation and protein expression of MYB, recently being considered to be an early and major oncogenic event in adenoid cystic carcinomas. Our data showed that the process of high-grade transformation is not always accompanied by an accumulation of genetic alterations; both conventional and transformed components harbored unique genetic alterations, which indicate a parallel progression. Our data further demonstrated that the MYB/NFIB translocation is not necessarily an early event or fundamental for the progression to adenoid cystic carcinoma with high-grade transformation.

Face and location processing in children with early unilateral brain injury.

PubMed

Paul, Brianna; Appelbaum, Mark; Carapetian, Stephanie; Hesselink, John; Nass, Ruth; Trauner, Doris; Stiles, Joan

2014-07-01

Human visuospatial functions are commonly divided into those dependent on the ventral visual stream (ventral occipitotemporal regions), which allows for processing the 'what' of an object, and the dorsal visual stream (dorsal occipitoparietal regions), which allows for processing 'where' an object is in space. Information about the development of each of the two streams has been accumulating, but very little is known about the effects of injury, particularly very early injury, on this developmental process. Using a set of computerized dorsal and ventral stream tasks matched for stimuli, required response, and difficulty (for typically-developing individuals), we sought to compare the differential effects of injury to the two systems by examining performance in individuals with perinatal brain injury (PBI), who present with selective deficits in visuospatial processing from a young age. Thirty participants (mean=15.1 years) with early unilateral brain injury (15 right hemisphere PBI, 15 left hemisphere PBI) and 16 matched controls participated. On our tasks children with PBI performed more poorly than controls (lower accuracy and longer response times), and this was particularly prominent for the ventral stream task. Lateralization of PBI was also a factor, as the dorsal stream task did not seem to be associated with lateralized deficits, with both PBI groups showing only subtle decrements in performance, while the ventral stream task elicited deficits from RPBI children that do not appear to improve with age. Our findings suggest that early injury results in lesion-specific visuospatial deficits that persist into adolescence. Further, as the stimuli used in our ventral stream task were faces, our findings are consistent with what is known about the neural systems for face processing, namely, that they are established relatively early, follow a comparatively rapid developmental trajectory (conferring a vulnerability to early insult), and are biased toward the right hemisphere. Copyright © 2014 Elsevier Inc. All rights reserved.

Chronology of Planetesimal Differentiation Based on the Timing of Achondrite Formation in the Early Solar System

NASA Astrophysics Data System (ADS)

Dunlap, D. R.; Wadhwa, M.

2018-05-01

Chronology of achondrites provide critical insights into accretion and differentiation timescales in the early solar system. A diverse suite of achondrites are presented here to constrain the thermal histories of a number of distinct planetesimals.

Comprehensive Cell-specific Protein Analysis in Early and Late Pollen Development from Diploid Microsporocytes to Pollen Tube Growth*

PubMed Central

Ischebeck, Till; Valledor, Luis; Lyon, David; Gingl, Stephanie; Nagler, Matthias; Meijón, Mónica; Egelhofer, Volker; Weckwerth, Wolfram

2014-01-01

Pollen development in angiosperms is one of the most important processes controlling plant reproduction and thus productivity. At the same time, pollen development is highly sensitive to environmental fluctuations, including temperature, drought, and nutrition. Therefore, pollen biology is a major focus in applied studies and breeding approaches for improving plant productivity in a globally changing climate. The most accessible developmental stages of pollen are the mature pollen and the pollen tubes, and these are thus most frequently analyzed. To reveal a complete quantitative proteome map, we additionally addressed the very early stages, analyzing eight stages of tobacco pollen development: diploid microsporocytes, meiosis, tetrads, microspores, polarized microspores, bipolar pollen, desiccated pollen, and pollen tubes. A protocol for the isolation of the early stages was established. Proteins were extracted and analyzed by means of a new gel LC-MS fractionation protocol. In total, 3817 protein groups were identified. Quantitative analysis was performed based on peptide count. Exceedingly stage-specific differential protein regulation was observed during the conversion from the sporophytic to the gametophytic proteome. A map of highly specialized functionality for the different stages could be revealed from the metabolic activity and pronounced differentiation of proteasomal and ribosomal protein complex composition up to protective mechanisms such as high levels of heat shock proteins in the very early stages of development. PMID:24078888

Comprehensive cell-specific protein analysis in early and late pollen development from diploid microsporocytes to pollen tube growth.

PubMed

Ischebeck, Till; Valledor, Luis; Lyon, David; Gingl, Stephanie; Nagler, Matthias; Meijón, Mónica; Egelhofer, Volker; Weckwerth, Wolfram

2014-01-01

Pollen development in angiosperms is one of the most important processes controlling plant reproduction and thus productivity. At the same time, pollen development is highly sensitive to environmental fluctuations, including temperature, drought, and nutrition. Therefore, pollen biology is a major focus in applied studies and breeding approaches for improving plant productivity in a globally changing climate. The most accessible developmental stages of pollen are the mature pollen and the pollen tubes, and these are thus most frequently analyzed. To reveal a complete quantitative proteome map, we additionally addressed the very early stages, analyzing eight stages of tobacco pollen development: diploid microsporocytes, meiosis, tetrads, microspores, polarized microspores, bipolar pollen, desiccated pollen, and pollen tubes. A protocol for the isolation of the early stages was established. Proteins were extracted and analyzed by means of a new gel LC-MS fractionation protocol. In total, 3817 protein groups were identified. Quantitative analysis was performed based on peptide count. Exceedingly stage-specific differential protein regulation was observed during the conversion from the sporophytic to the gametophytic proteome. A map of highly specialized functionality for the different stages could be revealed from the metabolic activity and pronounced differentiation of proteasomal and ribosomal protein complex composition up to protective mechanisms such as high levels of heat shock proteins in the very early stages of development.

Differential maturation of rhythmic clock gene expression during early development in medaka (Oryzias latipes).

PubMed

Cuesta, Ines H; Lahiri, Kajori; Lopez-Olmeda, Jose Fernando; Loosli, Felix; Foulkes, Nicholas S; Vallone, Daniela

2014-05-01

One key challenge for the field of chronobiology is to identify how circadian clock function emerges during early embryonic development. Teleosts such as the zebrafish are ideal models for studying circadian clock ontogeny since the entire process of development occurs ex utero in an optically transparent chorion. Medaka (Oryzias latipes) represents another powerful fish model for exploring early clock function with, like the zebrafish, many tools available for detailed genetic analysis. However, to date there have been no reports documenting circadian clock gene expression during medaka development. Here we have characterized the expression of key clock genes in various developmental stages and in adult tissues of medaka. As previously reported for other fish, light dark cycles are required for the emergence of clock gene expression rhythms in this species. While rhythmic expression of per and cry genes is detected very early during development and seems to be light driven, rhythmic clock and bmal expression appears much later around hatching time. Furthermore, the maturation of clock function seems to correlate with the appearance of rhythmic expression of these positive elements of the clock feedback loop. By accelerating development through elevated temperatures or by artificially removing the chorion, we show an earlier onset of rhythmicity in clock and bmal expression. Thus, differential maturation of key elements of the medaka clock mechanism depends on the developmental stage and the presence of the chorion.

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

The value of cyclooxygenase-2 expression in differentiating between early melanomas and histopathologically difficult types of benign human skin lesions.

PubMed

Kuźbicki, Łukasz; Lange, Dariusz; Strączyńska-Niemiec, Anita; Chwirot, Barbara W

2012-02-01

Early cutaneous melanomas may present a substantial diagnostic challenge. We have already reported that expression of cyclooxygenase-2 (COX-2) may be useful for differentiating between cutaneous melanomas and naevi. The purpose of this study was to examine the value of COX-2 in a challenging task of differential diagnosis of early melanomas and melanocytic naevi considered by histopathologists as morphologically difficult to unequivocally diagnose as benign lesions. The material for the study comprised formalin-fixed paraffin-embedded samples of 46 naevi (including 27 cases of dysplastic, Spitz and Reed naevi) and 30 early human cutaneous melanomas. The expression of COX-2 was detected immunohistochemically. Melanomas expressed COX-2 significantly more strongly compared with naevi. The test, on the basis of determination of the percentage fractions of COX-2-positive cells, allows for differentiation of early skin melanomas and naevi with high sensitivity and specificity. Receiver operating characteristic analysis of the test results yielded areas under receiver operating characteristics curves (AUC)=0.946±0.030 for central regions and AUC=0.941±0.031 for the peripheries of the lesions. The performance of the test in differentiating between melanomas and the naevi group comprising dysplastic, Spitz and Reed naevi was also good, with AUC=0.933±0.034 and 0.923±0.037 for the central and the border regions of the lesions, respectively. Using a more complex diagnostic algorithm also accounting for the staining intensity did not result in an improvement in the resolving power of the assay. A diagnostic algorithm using differences in the percentage fractions of cells expressing COX-2 may serve as a useful tool in aiding the differential diagnosis of 'histopathologically difficult' benign melanocytic skin lesions and early melanomas.

In vitro spatially organizing the differentiation in individual multicellular stem cell aggregates.

PubMed

Qi, Hao; Huang, Guoyou; Han, Yu Long; Lin, Wang; Li, Xiujun; Wang, Shuqi; Lu, Tian Jian; Xu, Feng

2016-01-01

With significant potential as a robust source to produce specific somatic cells for regenerative medicine, stem cells have attracted increasing attention from both academia and government. In vivo, stem cell differentiation is a process under complicated regulations to precisely build tissue with unique spatial structures. Since multicellular spheroidal aggregates of stem cells, commonly called as embryoid bodies (EBs), are considered to be capable of recapitulating the events in early stage of embryonic development, a variety of methods have been developed to form EBs in vitro for studying differentiation of embryonic stem cells. The regulation of stem cell differentiation is crucial in directing stem cells to build tissue with the correct spatial architecture for specific functions. However, stem cells within the three-dimensional multicellular aggregates undergo differentiation in a less unpredictable and spatially controlled manner in vitro than in vivo. Recently, various microengineering technologies have been developed to manipulate stem cells in vitro in a spatially controlled manner. Herein, we take the spotlight on these technologies and researches that bring us the new potential for manipulation of stem cells for specific purposes.

Extended Self-Renewal and Accelerated Reprogramming in the Absence of Kdm5b

PubMed Central

Hu, Gangqing; Yu, Zu-Xi; Liu, Chengyu

2013-01-01

Embryonic stem (ES) cell pluripotency is thought to be regulated in part by H3K4 methylation. However, it is unclear how H3K4 demethylation contributes to ES cell function and participates in induced pluripotent stem (iPS) cell reprogramming. Here, we show that KDM5B, which demethylates H3K4, is important for ES cell differentiation and presents a barrier to the reprogramming process. Depletion of Kdm5b leads to an extension in the self-renewal of ES cells in the absence of LIF. Transcriptome analysis revealed the persistent expression of pluripotency genes and underexpression of developmental genes during differentiation in the absence of Kdm5b, suggesting that KDM5B plays a key role in cellular fate changes. We also observed accelerated reprogramming of differentiated cells in the absence of Kdm5b, demonstrating that KDM5B is a barrier to the reprogramming process. Expression analysis revealed that mesenchymal master regulators associated with the epithelial-to-mesenchymal transition (EMT) are downregulated during reprogramming in the absence of Kdm5b. Moreover, global analysis of H3K4me3/2 revealed that enhancers of fibroblast genes are rapidly deactivated in the absence of Kdm5b, and genes associated with EMT lose H3K4me3/2 during the early reprogramming process. These findings provide functional insight into the role for KDM5B in regulating ES cell differentiation and as a barrier to the reprogramming process. PMID:24100015

RhoA Regulation of Cardiomyocyte Differentiation

PubMed Central

Kaarbø, Mari; Crane, Denis I.; Murrell, Wayne G.

2013-01-01

Earlier findings from our laboratory implicated RhoA in heart developmental processes. To investigate factors that potentially regulate RhoA expression, RhoA gene organisation and promoter activity were analysed. Comparative analysis indicated strict conservation of both gene organisation and coding sequence of the chick, mouse, and human RhoA genes. Bioinformatics analysis of the derived promoter region of mouse RhoA identified putative consensus sequence binding sites for several transcription factors involved in heart formation and organogenesis generally. Using luciferase reporter assays, RhoA promoter activity was shown to increase in mouse-derived P19CL6 cells that were induced to differentiate into cardiomyocytes. Overexpression of a dominant negative mutant of mouse RhoA (mRhoAN19) blocked this cardiomyocyte differentiation of P19CL6 cells and led to the accumulation of the cardiac transcription factors SRF and GATA4 and the early cardiac marker cardiac α-actin. Taken together, these findings indicate a fundamental role for RhoA in the differentiation of cardiomyocytes. PMID:23935420

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.

The microRNA-processing enzyme Dicer is essential for thyroid function.

PubMed

Frezzetti, Daniela; Reale, Carla; Calì, Gaetano; Nitsch, Lucio; Fagman, Henrik; Nilsson, Ola; Scarfò, Marzia; De Vita, Gabriella; Di Lauro, Roberto

2011-01-01

Dicer is a type III ribonuclease required for the biogenesis of microRNAs (miRNAs), a class of small non-coding RNAs regulating gene expression at the post-transcriptional level. To explore the functional role of miRNAs in thyroid gland function, we generated a thyrocyte-specific Dicer conditional knockout mouse. Here we show that development and early differentiation of the thyroid gland are not affected by the absence of Dicer, while severe hypothyroidism gradually develops after birth, leading to reduced body weight and shortened life span. Histological and molecular characterization of knockout mice reveals a dramatic loss of the thyroid gland follicular architecture associated with functional aberrations and down-regulation of several differentiation markers. The data presented in this study show for the first time that an intact miRNAs processing machinery is essential for thyroid physiology, suggesting that deregulation of specific miRNAs could be also involved in human thyroid dysfunctions.

Phase Equilibrium Investigations of Planetary Materials

NASA Technical Reports Server (NTRS)

Grove, T. L.

2005-01-01

This grant provided funds to carry out phase equilibrium studies on the processes of chemical differentiation of the moon and the meteorite parent bodies, during their early evolutionary history. Several experimental studies examined processes that led to the formation of lunar ultramafic glasses. Phase equilibrium studies were carried out on selected low-Ti and high-Ti lunar ultramafic glass compositions to provide constraints on the depth range, temperature and processes of melt generation and/or assimilation. A second set of experiments examined the role of sulfide melts in core formation processes in the earth and terrestrial planets. The major results of each paper are discussed, and copies of the papers are attached as Appendix I.

c-Myc-Induced Survivin Is Essential for Promoting the Notch-Dependent T Cell Differentiation from Hematopoietic Stem Cells

PubMed Central

Haque, Rizwanul; Song, Jianyong; Haque, Mohammad; Lei, Fengyang; Sandhu, Praneet; Ni, Bing; Zheng, Songguo; Fang, Deyu; Yang, Jin-Ming; Song, Jianxun

2017-01-01

Notch is indispensable for T cell lineage commitment, and is needed for thymocyte differentiation at early phases. During early stages of T cell development, active Notch prevents other lineage potentials including B cell lineage and myeloid cell (e.g., dendritic cell) lineage. Nevertheless, the precise intracellular signaling pathways by which Notch promotes T cell differentiation remain unclear. Here we report that the transcription factor c-Myc is a key mediator of the Notch signaling–regulated T cell differentiation. In a well-established in vitro differentiation model of T lymphocytes from hematopoietic stem cells, we showed that Notch1 and 4 directly promoted c-Myc expression; dominant-negative (DN) c-Myc inhibited early T cell differentiation. Moreover, the c-Myc expression activated by Notch signaling increased the expression of survivin, an inhibitor of apoptosis (IAP) protein. We further demonstrated that over-expression of c-Myc increased the abundance of survivin and the T cell differentiation thereof, whereas dn c-Myc reduced survivin levels and concomitantly retarded the differentiation. The c-Myc–dependent survivin induction is functionally germane, because Notch-dependent T cell differentiation was canceled by the depletion of survivin. These results identify both c-Myc and survivin as important mediators of the Notch signaling–regulated differentiation of T lymphocytes from hematopoietic stem cells. PMID:28272325

Experience-Dependent Hemispheric Specialization of Letters and Numbers is Revealed in Early Visual Processing

PubMed Central

Park, Joonkoo; Chiang, Crystal; Brannon, Elizabeth M.; Woldorff, Marty G.

2014-01-01

Recent functional magnetic resonance imaging research has demonstrated that letters and numbers are preferentially processed in distinct regions and hemispheres in the visual cortex. In particular, the left visual cortex preferentially processes letters compared to numbers, while the right visual cortex preferentially processes numbers compared to letters. Because letters and numbers are cultural inventions and are otherwise physically arbitrary, such a double dissociation is strong evidence for experiential effects on neural architecture. Here, we use the high temporal resolution of event-related potentials (ERPs) to investigate the temporal dynamics of the neural dissociation between letters and numbers. We show that the divergence between ERP traces to letters and numbers emerges very early in processing. Letters evoked greater N1 waves (latencies 140–170 ms) than did numbers over left occipital channels, while numbers evoked greater N1s than letters over the right, suggesting letters and numbers are preferentially processed in opposite hemispheres early in visual encoding. Moreover, strings of letters, but not single letters, elicited greater P2 ERP waves, (starting around 250 ms) than numbers did over the left hemisphere, suggesting that the visual cortex is tuned to selectively process combinations of letters, but not numbers, further along in the visual processing stream. Additionally, the processing of both of these culturally defined stimulus types differentiated from similar but unfamiliar visual stimulus forms (false fonts) even earlier in the processing stream (the P1 at 100 ms). These findings imply major cortical specialization processes within the visual system driven by experience with reading and mathematics. PMID:24669789

Experience-dependent hemispheric specialization of letters and numbers is revealed in early visual processing.

PubMed

Park, Joonkoo; Chiang, Crystal; Brannon, Elizabeth M; Woldorff, Marty G

2014-10-01

Recent fMRI research has demonstrated that letters and numbers are preferentially processed in distinct regions and hemispheres in the visual cortex. In particular, the left visual cortex preferentially processes letters compared with numbers, whereas the right visual cortex preferentially processes numbers compared with letters. Because letters and numbers are cultural inventions and are otherwise physically arbitrary, such a double dissociation is strong evidence for experiential effects on neural architecture. Here, we use the high temporal resolution of ERPs to investigate the temporal dynamics of the neural dissociation between letters and numbers. We show that the divergence between ERP traces to letters and numbers emerges very early in processing. Letters evoked greater N1 waves (latencies 140-170 msec) than did numbers over left occipital channels, whereas numbers evoked greater N1s than letters over the right, suggesting letters and numbers are preferentially processed in opposite hemispheres early in visual encoding. Moreover, strings of letters, but not single letters, elicited greater P2 ERP waves (starting around 250 msec) than numbers did over the left hemisphere, suggesting that the visual cortex is tuned to selectively process combinations of letters, but not numbers, further along in the visual processing stream. Additionally, the processing of both of these culturally defined stimulus types differentiated from similar but unfamiliar visual stimulus forms (false fonts) even earlier in the processing stream (the P1 at 100 msec). These findings imply major cortical specialization processes within the visual system driven by experience with reading and mathematics.

Coupled 142Nd-143Nd evidence for a protracted magma ocean in Mars.

PubMed

Debaille, V; Brandon, A D; Yin, Q Z; Jacobsen, B

2007-11-22

Resolving early silicate differentiation timescales is crucial for understanding the chemical evolution and thermal histories of terrestrial planets. Planetary-scale magma oceans are thought to have formed during early stages of differentiation, but the longevity of such magma oceans is poorly constrained. In Mars, the absence of vigorous convection and plate tectonics has limited the scale of compositional mixing within its interior, thus preserving the early stages of planetary differentiation. The SNC (Shergotty-Nakhla-Chassigny) meteorites from Mars retain 'memory' of these events. Here we apply the short-lived 146Sm-142Nd and the long-lived 147Sm-143Nd chronometers to a suite of shergottites to unravel the history of early silicate differentiation in Mars. Our data are best explained by progressive crystallization of a magma ocean with a duration of approximately 100 million years after core formation. This prolonged solidification requires the existence of a primitive thick atmosphere on Mars that reduces the cooling rate of the interior.

Quantitative proteomics and systems analysis of cultured H9C2 cardiomyoblasts during differentiation over time supports a 'function follows form' model of differentiation.

PubMed

Kankeu, Cynthia; Clarke, Kylie; Van Haver, Delphi; Gevaert, Kris; Impens, Francis; Dittrich, Anna; Roderick, H Llewelyn; Passante, Egle; Huber, Heinrich J

2018-05-17

The rat cardiomyoblast cell line H9C2 has emerged as a valuable tool for studying cardiac development, mechanisms of disease and toxicology. We present here a rigorous proteomic analysis that monitored the changes in protein expression during differentiation of H9C2 cells into cardiomyocyte-like cells over time. Quantitative mass spectrometry followed by gene ontology (GO) enrichment analysis revealed that early changes in H9C2 differentiation are related to protein pathways of cardiac muscle morphogenesis and sphingolipid synthesis. These changes in the proteome were followed later in the differentiation time-course by alterations in the expression of proteins involved in cation transport and beta-oxidation. Studying the temporal profile of the H9C2 proteome during differentiation in further detail revealed eight clusters of co-regulated proteins that can be associated with early, late, continuous and transient up- and downregulation. Subsequent reactome pathway analysis based on these eight clusters further corroborated and detailed the results of the GO analysis. Specifically, this analysis confirmed that proteins related to pathways in muscle contraction are upregulated early and transiently, and proteins relevant to extracellular matrix organization are downregulated early. In contrast, upregulation of proteins related to cardiac metabolism occurs at later time points. Finally, independent validation of the proteomics results by immunoblotting confirmed hereto unknown regulators of cardiac structure and ionic metabolism. Our results are consistent with a 'function follows form' model of differentiation, whereby early and transient alterations of structural proteins enable subsequent changes that are relevant to the characteristic physiology of cardiomyocytes.

The ADAMTS5 Metzincin Regulates Zebrafish Somite Differentiation

PubMed Central

Dancevic, Carolyn M.; Gibert, Yann; Smith, Adam D.; Ward, Alister C.; McCulloch, Daniel R.

2018-01-01

The ADAMTS5 metzincin, a secreted zinc-dependent metalloproteinase, modulates the extracellular matrix (ECM) during limb morphogenesis and other developmental processes. Here, the role of ADAMTS5 was investigated by knockdown of zebrafish adamts5 during embryogenesis. This revealed impaired Sonic Hedgehog (Shh) signaling during somite patterning and early myogenesis. Notably, synergistic regulation of myod expression by ADAMTS5 and Shh during somite differentiation was observed. These roles were not dependent upon the catalytic activity of ADAMTS5. These data identify a non-enzymatic function for ADAMTS5 in regulating an important cell signaling pathway that impacts on muscle development, with implications for musculoskeletal diseases in which ADAMTS5 and Shh have been associated. PMID:29518972

Effects of early focal brain injury on memory for visuospatial patterns: selective deficits of global-local processing.

PubMed

Stiles, Joan; Stern, Catherine; Appelbaum, Mark; Nass, Ruth; Trauner, Doris; Hesselink, John

2008-01-01

Selective deficits in visuospatial processing are present early in development among children with perinatal focal brain lesions (PL). Children with right hemisphere PL (RPL) are impaired in configural processing, while children with left hemisphere PL (LPL) are impaired in featural processing. Deficits associated with LPL are less pervasive than those observed with RPL, but this difference may reflect the structure of the tasks used for assessment. Many of the tasks used to date may place greater demands on configural processing, thus highlighting this deficit in the RPL group. This study employed a task designed to place comparable demands on configural and featural processing, providing the opportunity to obtain within-task evidence of differential deficit. Sixty-two 5- to 14-year-old children (19 RPL, 19 LPL, and 24 matched controls) reproduced from memory a series of hierarchical forms (large forms composed of small forms). Global- and local-level reproduction accuracy was scored. Controls were equally accurate on global- and local-level reproduction. Children with RPL were selectively impaired on global accuracy, and children with LPL on local accuracy, thus documenting a double dissociation in global-local processing.

Evaluation of biological effects of intermediate frequency magnetic field on differentiation of embryonic stem cell.

PubMed

Yoshie, Sachiko; Ogasawara, Yuki; Ikehata, Masateru; Ishii, Kazuyuki; Suzuki, Yukihisa; Wada, Keiji; Wake, Kanako; Nakasono, Satoshi; Taki, Masao; Ohkubo, Chiyoji

2016-01-01

The embryotoxic effect of intermediate frequency (IF) magnetic field (MF) was evaluated using murine embryonic stem (ES) cells and fibroblast cells based on the embryonic stem cell test (EST). The cells were exposed to 21 kHz IF-MF up to magnetic flux density of 3.9 mT during the cell proliferation process (7 days) or the cell differentiation process (10 days) during which an embryonic body differentiated into myocardial cells. As a result, there was no significant difference in the cell proliferation between sham- and IF-MF-exposed cells for both ES and fibroblast cells. Similarly, the ratio of the number of ES-derived cell aggregates differentiated to myocardial cells to total number of cell aggregates was not changed by IF-MF exposure. In addition, the expressions of a cardiomyocytes-specific gene, Myl2 , and an early developmental gene, Hba-x , in the exposed cell aggregate were not altered. Since the magnetic flux density adopted in this study is much higher than that generated by an inverter of the electrical railway, an induction heating (IH) cooktop, etc . in our daily lives, these results suggested that IF-MF in which the public is exposed to in general living environment would not have embryotoxic effect.

Fear-potentiated startle processing in humans: Parallel fMRI and orbicularis EMG assessment during cue conditioning and extinction.

PubMed

Lindner, Katja; Neubert, Jörg; Pfannmöller, Jörg; Lotze, Martin; Hamm, Alfons O; Wendt, Julia

2015-12-01

Studying neural networks and behavioral indices such as potentiated startle responses during fear conditioning has a long tradition in both animal and human research. However, most of the studies in humans do not link startle potentiation and neural activity during fear acquisition and extinction. Therefore, we examined startle blink responses measured with electromyography (EMG) and brain activity measured with functional MRI simultaneously during differential conditioning. Furthermore, we combined these behavioral fear indices with brain network activity by analyzing the brain activity evoked by the startle probe stimulus presented during conditioned visual threat and safety cues as well as in the absence of visual stimulation. In line with previous research, we found a fear-induced potentiation of the startle blink responses when elicited during a conditioned threat stimulus and a rapid decline of amygdala activity after an initial differentiation of threat and safety cues in early acquisition trials. Increased activation during processing of threat cues was also found in the anterior insula, the anterior cingulate cortex (ACC), and the periaqueductal gray (PAG). More importantly, our results depict an increase of brain activity to probes presented during threatening in comparison to safety cues indicating an involvement of the anterior insula, the ACC, the thalamus, and the PAG in fear-potentiated startle processing during early extinction trials. Our study underlines that parallel assessment of fear-potentiated startle in fMRI paradigms can provide a helpful method to investigate common and distinct processing pathways in humans and animals and, thus, contributes to translational research. Copyright © 2015 Elsevier B.V. All rights reserved.

Genome Wide assessment of Early Osseointegration in Implant-Adherent Cells

NASA Astrophysics Data System (ADS)

Thalji, Ghadeer N.

Objectives: To determine the molecular processes involved in osseointegration. Materials and methods: A structured literature review concerning in vitro and in vivo molecular assessment of osseointegration was performed. A rat and a human model were then used to identify the early molecular processes involved in osseointegration associated with a micro roughened and nanosurface superimposed featured implants. In the rat model, 32 titanium implants with surface topographies exhibiting a micro roughened (AT-II) and nanosurface superimposed featured implants (AT-I) were placed in the tibiae of 8 rats and subsequently harvested at 2 and 4 days after placement. Whereas in the human model, four titanium mini-implants with either a moderately roughened surface (TiOblast) or super-imposed nanoscale topography (Osseospeed) were placed in edentulous sites of eleven systemically healthy subjects and subsequently removed after 3 and 7 days. Total RNA was isolated from cells adherent to retrieved implants. A whole genome microarray using the Affymetrix 1.1 ST Array platform was used to describe the gene expression profiles that were differentially regulated by the implant surfaces. Results: The literature review provided evidence that particular topographic cues can be specifically integrated among the many extracellular signals received by the cell in its signal transduction network. In the rat model, functionally relevant categories related to ossification, skeletal system development, osteoblast differentiation, bone development and biomineral tissue development were upregulated and more prominent at AT-I compared to AT-II. In the human model, there were no significant differences when comparing the two-implant surfaces at each time point. However, the microarray identified several genes that were differentially regulated at day 7 vs. day 3 for both implant surfaces. Functionally relevant categories related to the extracellular matrix, collagen fibril organization and angiogenesis were upregulated at both surfaces. Abundant upregulation of several differential markers of alternative activated macrophages was also observed. The biological processes involved with the inflammatory/immune response gene expression were concomitantly downregulated. Conclusions: The presence of micro-roughened and nanosurface features modulated in vivo bone response. This work confirms previous evaluations and further implicates modulation of the inflammatory/immune responses as a factor affecting the accrual of bone mass shortly after implant placement.

Implicit and explicit categorization of natural scenes.

PubMed

Codispoti, Maurizio; Ferrari, Vera; De Cesarei, Andrea; Cardinale, Rossella

2006-01-01

Event-related potential (ERP) studies have consistently found that emotionally arousing (pleasant and unpleasant) pictures elicit a larger late positive potential (LPP) than neutral pictures in a window from 400 to 800 ms after picture onset. In addition, an early ERP component has been reported to vary with emotional arousal in a window from about 150 to 300 ms with affective, compared to neutral stimuli, prompting significantly less positivity over occipito-temporal sites. Similar early and late ERP components have been found in explicit categorization tasks, suggesting that selective attention to target features results in similar cortical changes. Several studies have shown that the affective modulation of the LPP persisted even when the same pictures are repeated several times, when they are presented as distractors, or when participants are engaged in a competing task. These results indicate that categorization of affective stimuli is an obligatory process. On the other hand, perceptual factors (e.g., stimulus size) seem to affect the early ERP component but not the affective modulation of the LPP. Although early and late ERP components vary with stimulus relevance, given that they are differentially affected by stimulus and task manipulations, they appear to index different facets of picture processing.

Stochastic and epigenetic changes of gene expression in Arabidopsis polyploids.

PubMed

Wang, Jianlin; Tian, Lu; Madlung, Andreas; Lee, Hyeon-Se; Chen, Meng; Lee, Jinsuk J; Watson, Brian; Kagochi, Trevor; Comai, Luca; Chen, Z Jeffrey

2004-08-01

Polyploidization is an abrupt speciation mechanism for eukaryotes and is especially common in plants. However, little is known about patterns and mechanisms of gene regulation during early stages of polyploid formation. Here we analyzed differential expression patterns of the progenitors' genes among successive selfing generations and independent lineages. The synthetic Arabidopsis allotetraploid lines were produced by a genetic cross between A. thaliana and A. arenosa autotetraploids. We found that some progenitors' genes are differentially expressed in early generations, whereas other genes are silenced in late generations or among different siblings within a selfing generation, suggesting that the silencing of progenitors' genes is rapidly and/or stochastically established. Moreover, a subset of genes is affected in autotetraploid and multiple independent allotetraploid lines and in A. suecica, a natural allotetraploid derived from A. thaliana and A. arenosa, indicating locus-specific susceptibility to ploidy-dependent gene regulation. The role of DNA methylation in silencing progenitors' genes is tested in DNA-hypomethylation transgenic lines of A. suecica using RNA interference (RNAi). Two silenced genes are reactivated in both ddm1- and met1-RNAi lines, consistent with the demethylation of centromeric repeats and gene-specific regions in the genome. A rapid and stochastic process of differential gene expression is reinforced by epigenetic regulation during polyploid formation and evolution. Copyright 2004 Genetics Society of America

Atheroprotection through SYK inhibition fails in established disease when local macrophage proliferation dominates lesion progression.

PubMed

Lindau, Alexandra; Härdtner, Carmen; Hergeth, Sonja P; Blanz, Kelly Daryll; Dufner, Bianca; Hoppe, Natalie; Anto-Michel, Nathaly; Kornemann, Jan; Zou, Jiadai; Gerhardt, Louisa M S; Heidt, Timo; Willecke, Florian; Geis, Serjosha; Stachon, Peter; Wolf, Dennis; Libby, Peter; Swirski, Filip K; Robbins, Clinton S; McPheat, William; Hawley, Shaun; Braddock, Martin; Gilsbach, Ralf; Hein, Lutz; von zur Mühlen, Constantin; Bode, Christoph; Zirlik, Andreas; Hilgendorf, Ingo

2016-03-01

Macrophages in the arterial intima sustain chronic inflammation during atherogenesis. Under hypercholesterolemic conditions murine Ly6C(high) monocytes surge in the blood and spleen, infiltrate nascent atherosclerotic plaques, and differentiate into macrophages that proliferate locally as disease progresses. Spleen tyrosine kinase (SYK) may participate in downstream signaling of various receptors that mediate these processes. We tested the effect of the SYK inhibitor fostamatinib on hypercholesterolemia-associated myelopoiesis and plaque formation in Apoe(-/-) mice during early and established atherosclerosis. Mice consuming a high cholesterol diet supplemented with fostamatinib for 8 weeks developed less atherosclerosis. Histologic and flow cytometric analysis of aortic tissue showed that fostamatinib reduced the content of Ly6C(high) monocytes and macrophages. SYK inhibition limited Ly6C(high) monocytosis through interference with GM-CSF/IL-3 stimulated myelopoiesis, attenuated cell adhesion to the intimal surface, and blocked M-CSF stimulated monocyte to macrophage differentiation. In Apoe(-/-) mice with established atherosclerosis, however, fostamatinib treatment did not limit macrophage accumulation or lesion progression despite a significant reduction in blood monocyte counts, as lesional macrophages continued to proliferate. Thus, inhibition of hypercholesterolemia-associated monocytosis, monocyte infiltration, and differentiation by SYK antagonism attenuates early atherogenesis but not established disease when local macrophage proliferation dominates lesion progression.

Differential proteomic analysis of Aspergillus fumigatus morphotypes reveals putative drug targets.

PubMed

Kubitschek-Barreira, Paula H; Curty, Nathalia; Neves, Gabriela W P; Gil, Concha; Lopes-Bezerra, Leila M

2013-01-14

Aspergillus fumigatus is the main etiological agent of invasive aspergillosis, an important opportunistic infection for neutropenic patients. The main risk groups are patients with acute leukemia and bone marrow transplantation recipients. The lack of an early diagnostic test together with the limited spectrum of antifungal drugs remains a setback to the successful treatment of this disease. During invasive infection the inhaled fungal conidia enter the morphogenic cycle leading to angioinvasive hyphae. This work aimed to study differentially expressed proteins of A. fumigatus during morphogenesis. To achieve this goal, a 2D-DIGE approach was applied to study surface proteins extractable by reducing agents of two A. fumigatus morphotypes: germlings and hyphae. Sixty-three differentially expressed proteins were identified by MALDI-ToF/MS. We observed that proteins associated with biosynthetic pathways and proteins with multiple functions (miscellaneous) were over-expressed in the early stages of germination, while in hyphae, the most abundant proteins detected were related to metabolic processes or have unknown functions. Among the most interesting proteins regulated during morphogenesis, two putative drug targets were identified, the translational factor, eEF3 and the CipC-like protein. Neither of these proteins are present in mammalian cells. Copyright © 2012 Elsevier B.V. All rights reserved.

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

A Screening Mechanism Differentiating True from False Pain during Empathy.

PubMed

Sun, Ya-Bin; Lin, Xiao-Xiao; Ye, Wen; Wang, Ning; Wang, Jin-Yan; Luo, Fei

2017-09-13

Empathizing with another's suffering is important in social interactions. Empathic behavior is selectively elicited from genuine, meaningful pain but not from fake, meaningless scenarios. However, the brain's screening mechanism of false information from meaningful events and the time course for the screening process remains unclear. Using EEG combined with principle components analysis (PCA) techniques, here we compared temporal neurodynamics between the observation of pain and no-pain pictures as well as between true (painful expressions and needle-penetrated arms) and false (needle-penetrated faces with neutral expressions) pain pictures. The results revealed that pain vs. no-pain information is differentiated in the very early ERP components, i.e., the N1/P1 for the face and arm pictures categories and the VPP/N170 for the facial expression category while the mid-latency ERP components, N2 and P3, played key roles in differentiating true from false situations. The complex of N2 and P3 components may serve as a screening mechanism through which observers allocate their attentions to more important or relevant events and screen out false environmental information. This is the first study to describe and provide a time course of the screening process during pain empathy. These findings shed new light on the understanding of empathic processing.

Genetic drift and rapid evolution of viviparity in insular fire salamanders (Salamandra salamandra)

PubMed Central

Velo-Antón, G; Zamudio, K R; Cordero-Rivera, A

2012-01-01

Continental islands offer an excellent opportunity to investigate adaptive processes and to time microevolutionary changes that precede macroevolutionary events. We performed a population genetic study of the fire salamander (Salamandra salamandra), a species that displays unique intraspecific diversity of reproductive strategies, to address the microevolutionary processes leading to phenotypic and genetic differentiation of island, coastal and interior populations. We used eight microsatellite markers to estimate genetic diversity, population structure and demographic parameters in viviparous insular populations and ovoviviparous coastal and interior populations. Our results show considerable genetic differentiation (FST range: 0.06–0.27), and no clear signs of gene flow among populations, except between the large and admixed interior populations. We find no support for island colonization by rafting or intentional/accidental anthropogenic introductions, indicating that rising sea levels were responsible for isolation of the island populations approximately 9000 years ago. Our study provides evidence of rapid genetic differentiation between island and coastal populations, and rapid evolution of viviparity driven by climatic selective pressures on island populations, geographic isolation with genetic drift, or a combination of these factors. Studies of these viviparous island populations in early stages of divergence help us better understand the microevolutionary processes involved in rapid phenotypic shifts. PMID:22086081

Genetic drift and rapid evolution of viviparity in insular fire salamanders (Salamandra salamandra).

PubMed

Velo-Antón, G; Zamudio, K R; Cordero-Rivera, A

2012-04-01

Continental islands offer an excellent opportunity to investigate adaptive processes and to time microevolutionary changes that precede macroevolutionary events. We performed a population genetic study of the fire salamander (Salamandra salamandra), a species that displays unique intraspecific diversity of reproductive strategies, to address the microevolutionary processes leading to phenotypic and genetic differentiation of island, coastal and interior populations. We used eight microsatellite markers to estimate genetic diversity, population structure and demographic parameters in viviparous insular populations and ovoviviparous coastal and interior populations. Our results show considerable genetic differentiation (F(ST) range: 0.06-0.27), and no clear signs of gene flow among populations, except between the large and admixed interior populations. We find no support for island colonization by rafting or intentional/accidental anthropogenic introductions, indicating that rising sea levels were responsible for isolation of the island populations approximately 9000 years ago. Our study provides evidence of rapid genetic differentiation between island and coastal populations, and rapid evolution of viviparity driven by climatic selective pressures on island populations, geographic isolation with genetic drift, or a combination of these factors. Studies of these viviparous island populations in early stages of divergence help us better understand the microevolutionary processes involved in rapid phenotypic shifts.

Active form Notch4 promotes the proliferation and differentiation of 3T3-L1 preadipocytes

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

Lai, Peng-Yeh; Tsai, Chong-Bin; Department of Ophthalmology, Chiayi Christian Hospital, Chiayi 600, Taiwan, ROC

2013-01-18

Highlights: ► Notch4IC modulates the ERK pathway and cell cycle to promote 3T3-L1 proliferation. ► Notch4IC facilitates 3T3-L1 differentiation by up-regulating proadipogenic genes. ► Notch4IC promotes proliferation during the early stage of 3T3-L1 adipogenesis. ► Notch4IC enhances differentiation during subsequent stages of 3T3-L1 adipogenesis. -- Abstract: Adipose tissue is composed of adipocytes, which differentiate from precursor cells in a process called adipogenesis. Many signal molecules are involved in the transcriptional control of adipogenesis, including the Notch pathway. Previous adipogenic studies of Notch have focused on Notch1 and HES1; however, the role of other Notch receptors in adipogenesis remains unclear. Q-RT-PCRmore » analyses showed that the augmentation of Notch4 expression during the differentiation of 3T3-L1 preadipocytes was comparable to that of Notch1. To elucidate the role of Notch4 in adipogenesis, the human active form Notch4 (N4IC) was transiently transfected into 3T3-L1 cells. The expression of HES1, Hey1, C/EBPδ and PPARγ was up-regulated, and the expression of Pref-1, an adipogenic inhibitor, was down-regulated. To further characterize the effect of N4IC in adipogenesis, stable cells expressing human N4IC were established. The expression of N4IC promoted proliferation and enhanced differentiation of 3T3-L1 cells compared with those of control cells. These data suggest that N4IC promoted proliferation through modulating the ERK pathway and the cell cycle during the early stage of 3T3-L1 adipogenesis and facilitated differentiation through up-regulating adipogenic genes such as C/EBPα, PPARγ, aP2, LPL and HSL during the middle and late stages of 3T3-L1 adipogenesis.« less

Impact of Early Life Adversity on Reward Processing in Young Adults: EEG-fMRI Results from a Prospective Study over 25 Years

PubMed Central

Boecker, Regina; Holz, Nathalie E.; Buchmann, Arlette F.; Blomeyer, Dorothea; Plichta, Michael M.; Wolf, Isabella; Baumeister, Sarah; Meyer-Lindenberg, Andreas; Banaschewski, Tobias

2014-01-01

Several lines of evidence have implicated the mesolimbic dopamine reward pathway in altered brain function resulting from exposure to early adversity. The present study examined the impact of early life adversity on different stages of neuronal reward processing later in life and their association with a related behavioral phenotype, i.e. attention deficit/hyperactivity disorder (ADHD). 162 healthy young adults (mean age = 24.4 years; 58% female) from an epidemiological cohort study followed since birth participated in a simultaneous EEG-fMRI study using a monetary incentive delay task. Early life adversity according to an early family adversity index (EFA) and lifetime ADHD symptoms were assessed using standardized parent interviews conducted at the offspring's age of 3 months and between 2 and 15 years, respectively. fMRI region-of-interest analysis revealed a significant effect of EFA during reward anticipation in reward-related areas (i.e. ventral striatum, putamen, thalamus), indicating decreased activation when EFA increased. EEG analysis demonstrated a similar effect for the contingent negative variation (CNV), with the CNV decreasing with the level of EFA. In contrast, during reward delivery, activation of the bilateral insula, right pallidum and bilateral putamen increased with EFA. There was a significant association of lifetime ADHD symptoms with lower activation in the left ventral striatum during reward anticipation and higher activation in the right insula during reward delivery. The present findings indicate a differential long-term impact of early life adversity on reward processing, implicating hyporesponsiveness during reward anticipation and hyperresponsiveness when receiving a reward. Moreover, a similar activation pattern related to lifetime ADHD suggests that the impact of early life stress on ADHD may possibly be mediated by a dysfunctional reward pathway. PMID:25118701

Usefulness of Demarcation of Differentiated-Type Early Gastric Cancers after Helicobacter pylori Eradication by Magnifying Endoscopy with Narrow-Band Imaging.

PubMed

Akazawa, Yoichi; Ueyama, Hiroya; Yao, Takashi; Komori, Hiroyuki; Takeda, Tsutomu; Matsumoto, Kohei; Matsumoto, Kenshi; Asaoka, Daisuke; Hojo, Mariko; Watanabe, Sumio; Nagahara, Akihito

2018-06-05

Early gastric cancer after Helicobacter pylori (Hp) eradication is difficult to demarcate. We used the vessel plus surface classification system (VSCS) to determine whether magnifying endoscopy with narrow-band imaging (ME-NBI) could demarcate differentiated-type early gastric cancers after Hp eradication, and to identify causes of an unclear demarcation line (DL). Among 100 lesions of differentiated-type early gastric cancer resected endoscopically, 34 lesions in the Hp-eradicated group and 66 in the Hp-infected group were retrospectively compared. Clinicopathological factors and ME-NBI findings, including the presence or absence of the DL, were examined. Histopathologically, histological gastritis, the surface structure at the tumor border, well-differentiated adenocarcinoma with low-grade atypia (tub1-low), and non-neoplastic epithelium (NE) coverage rate on the tumor surface and at the tumor border were evaluated. DL (-) cases were more frequent in the Hp-eradicated group (11.8%, 4/34) than in the Hp-infected group (1.5%, 1/66; p < 0.05). The Hp-eradicated group had a higher NE coverage rate than the Hp-infected group (p < 0.05). All DL (-) cases had tub1-low or NE at the tumor border. ME-NBI with VSCS can identify the DL in most patients (88.2%) with differentiated-type early gastric cancer after Hp eradication. © 2018 S. Karger AG, Basel.

Extraocular muscle regeneration in zebrafish requires late signals from Insulin-like growth factors.

PubMed

Saera-Vila, Alfonso; Louie, Ke'ale W; Sha, Cuilee; Kelly, Ryan M; Kish, Phillip E; Kahana, Alon

2018-01-01

Insulin-like growth factors (Igfs) are key regulators of key biological processes such as embryonic development, growth, and tissue repair and regeneration. The role of Igf in myogenesis is well documented and, in zebrafish, promotes fin and heart regeneration. However, the mechanism of action of Igf in muscle repair and regeneration is not well understood. Using adult zebrafish extraocular muscle (EOM) regeneration as an experimental model, we show that Igf1 receptor blockage using either chemical inhibitors (BMS754807 and NVP-AEW541) or translation-blocking morpholino oligonucleotides (MOs) reduced EOM regeneration. Zebrafish EOMs regeneration depends on myocyte dedifferentiation, which is driven by early epigenetic reprogramming and requires autophagy activation and cell cycle reentry. Inhibition of Igf signaling had no effect on either autophagy activation or cell proliferation, indicating that Igf signaling was not involved in the early reprogramming steps of regeneration. Instead, blocking Igf signaling produced hypercellularity of regenerating EOMs and diminished myosin expression, resulting in lack of mature differentiated muscle fibers even many days after injury, indicating that Igf was involved in late re-differentiation steps. Although it is considered the main mediator of myogenic Igf actions, Akt activation decreased in regenerating EOMs, suggesting that alternative signaling pathways mediate Igf activity in muscle regeneration. In conclusion, Igf signaling is critical for re-differentiation of reprogrammed myoblasts during late steps of zebrafish EOM regeneration, suggesting a regulatory mechanism for determining regenerated muscle size and timing of differentiation, and a potential target for regenerative therapy.

[Thyroid hormones and the development of the nervous system].

PubMed

Mussa, G C; Zaffaroni, M; Mussa, F

1990-09-01

The growth and differentiation of the central nervous system are closely related to the presence of iodine and thyroid hormones. During the first trimester of human pregnancy the development of the nervous system depends entirely on the availability of iodine; after 12 week of pregnancy it depends on the initial secretion of iodothyronine by the fetal thyroid gland. During the early stages of the development of the nervous system a thyroid hormone deficit may provoke alterations in the maturation of both noble nervous cells (cortical pyramidal cells, Purkinje cells) and glial cells. Hypothyroidism may lead to cellular hypoplasia and reduced dendritic ramification, gemmules and interneuronal connections. Experimental studies in hypothyroid rats have also shown alterations in the content and organization of neuronal intracytoplasmatic microtubules, the biochemical maturation of synaptosomes and the maturation of nuclear and cytoplasmatic T3 receptors. Excess thyroid hormones during the early stages of development may also cause permanent damage to the central nervous system. Hyperthyroidism may initially induce an acceleration of the maturation processes, including the migration and differentiation of cells, the extension of the dendritic processes and synaptogenesis. An excess of thyroid hormones therefore causes neuronal proliferation to end precociously leading to a reduction of the total number of gemmules. Experimental research and clinical studies have partially clarified the correlation between the maturation of the nervous system and thyroid function during the early stages of development; both a deficit and excess of thyroid hormones may lead to permanent anatomo-functional damage to the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)

Tracking Hadean processes in modern basalts with 142-Neodymium

NASA Astrophysics Data System (ADS)

Horan, M. F.; Carlson, R. W.; Walker, R. J.; Jackson, M.; Garçon, M.; Norman, M.

2018-02-01

The short-lived 146Sm→142 Nd isotope system (t1/2 = 103 Ma) provides constraints on the timing and processes of terrestrial silicate fractionation during the early Hadean. Although some Archean terranes preserve variability in 142Nd/144Nd, no anomalies have been resolved previously in young rocks. This study provides high precision 142Nd/144Nd data on a suite of ocean island basalts from Samoa and Hawaii previously shown to have variable depletions in 182W/184W that are inversely correlated with 3He/4He ratios. Improved analytical techniques and multiple replicate analyses of Nd show a variation in μ142 Nd values between -1.3 and +2.7 in the suite, relative to the JNdi standard. Given the reproducibility of the standard (±2.9 ppm, 2 SD), two Samoan samples exhibit resolved variability in their 142Nd/144Nd ratios outside of their 95% confidence intervals, suggesting minor variability in the Samoan hotspot. One sample from Samoa has a higher μ142 Nd of +2.7, outside the 95% confidence interval (±1.0 ppm) of the average of the JNdi standard. Limited, but resolved, variation in 142Nd/144Nd within the suite suggests the preservation of early Hadean silicate differentiation in the sources of at least some basalts from Samoa. Larger variations of 182W/184W and 3He/4He ratios in the same samples suggest that metal-silicate separation and mantle outgassing left a more persistent imprint on the accessible mantle compared to 142Nd/144Nd ratios which are impacted by early silicate differentiation.

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.

Emotional conflict occurs at an early stage: evidence from the emotional face-word Stroop task.

PubMed

Zhu, Xiang-ru; Zhang, Hui-jun; Wu, Ting-ting; Luo, Wen-bo; Luo, Yue-jia

2010-06-30

The perceptual processing of emotional conflict was studied using electrophysiological techniques to measure event-related potentials (ERPs). The emotional face-word Stroop task in which emotion words are written in prominent red color across a face was use to study emotional conflict. In each trial, the emotion word and facial expression were either congruent or incongruent (in conflict). When subjects were asked to identify the expression of the face during a trial, the incongruent condition evoked a more negative N170 ERP component in posterior lateral sites than in the congruent condition. In contrast, when subjects were asked to identify the word during a trial, the incongruent condition evoked a less negative N170 component than the congruent condition. The present findings extend our understanding of the control processes involved in emotional conflict by demonstrating that differentiation of emotional congruency begins at an early perceptual processing stage. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Rodent Zic Genes in Neural Network Wiring.

PubMed

Herrera, Eloísa

2018-01-01

The formation of the nervous system is a multistep process that yields a mature brain. Failure in any of the steps of this process may cause brain malfunction. In the early stages of embryonic development, neural progenitors quickly proliferate and then, at a specific moment, differentiate into neurons or glia. Once they become postmitotic neurons, they migrate to their final destinations and begin to extend their axons to connect with other neurons, sometimes located in quite distant regions, to establish different neural circuits. During the last decade, it has become evident that Zic genes, in addition to playing important roles in early development (e.g., gastrulation and neural tube closure), are involved in different processes of late brain development, such as neuronal migration, axon guidance, and refinement of axon terminals. ZIC proteins are therefore essential for the proper wiring and connectivity of the brain. In this chapter, we review our current knowledge of the role of Zic genes in the late stages of neural circuit formation.

Pupillary responses reveal infants' discrimination of facial emotions independent of conscious perception.

PubMed

Jessen, Sarah; Altvater-Mackensen, Nicole; Grossmann, Tobias

2016-05-01

Sensitive responding to others' emotions is essential during social interactions among humans. There is evidence for the existence of subcortically mediated emotion discrimination processes that occur independent of conscious perception in adults. However, only recently work has begun to examine the development of automatic emotion processing systems during infancy. In particular, it is unclear whether emotional expressions impact infants' autonomic nervous system regardless of conscious perception. We examined this question by measuring pupillary responses while subliminally and supraliminally presenting 7-month-old infants with happy and fearful faces. Our results show greater pupil dilation, indexing enhanced autonomic arousal, in response to happy compared to fearful faces regardless of conscious perception. Our findings suggest that, early in ontogeny, emotion discrimination occurs independent of conscious perception and is associated with differential autonomic responses. This provides evidence for the view that automatic emotion processing systems are an early-developing building block of human social functioning. Copyright © 2016 Elsevier B.V. All rights reserved.

TALE transcription factors during early development of the vertebrate brain and eye.

PubMed

Schulte, Dorothea; Frank, Dale

2014-01-01

Our brain's cognitive performance arises from the coordinated activities of billions of nerve cells. Despite a high degree of morphological and functional differences, all neurons of the vertebrate central nervous system (CNS) arise from a common field of multipotent progenitors. Cell fate specification and differentiation are directed by multistep processes that include inductive/external cues, such as the extracellular matrix or growth factors, and cell-intrinsic determinants, such as transcription factors and epigenetic modulators of proteins and DNA. Here we review recent findings implicating TALE-homeodomain proteins in these processes. Although originally identified as HOX-cofactors, TALE proteins also contribute to many physiological processes that do not require HOX-activity. Particular focus is, therefore, given to HOX-dependent and -independent functions of TALE proteins during early vertebrate brain development. Additionally, we provide an overview about known upstream and downstream factors of TALE proteins in the developing vertebrate brain and discuss general concepts of how TALE proteins function to modulate neuronal cell fate specification. Copyright © 2013 Wiley Periodicals, Inc.

Neural Responses to Partner Rejection Cues

PubMed Central

Zayas, Vivian; Shoda, Yuichi; Mischel, Walter; Osterhout, Lee; Takahashi, Melissa

2009-01-01

Little is known about neural responses in the early automatic-stage processing of rejection cues from a partner. Event-related potentials (ERPs) offer a window to study processes that may be difficult to detect via behavioral methods. We focused on the N400 ERP component, which reflects the amount of semantic processing prompted by a target. When participants were primed by attachment-related contexts (“If I need help from my partner, my partner will be …”), rejection-related words (e.g., dismissing) elicited greater N400 amplitudes than acceptance-related words (e.g., supporting). Analyses of results for nonattachment primes suggest that these findings were not simply caused by target valence; the brain responds differentially to cues of partner rejection versus acceptance in under 300 ms. Moreover, these early-stage neurophysiological responses were heightened or dampened as a function of individuals’ adult attachment; women characterized by high anxiety and low avoidance showed the greatest N400 responses to cues of partner rejection (vs. acceptance). PMID:19493321

Mitophagy is required for mitochondrial biogenesis and myogenic differentiation of C2C12 myoblasts.

PubMed

Sin, Jon; Andres, Allen M; Taylor, David J R; Weston, Thomas; Hiraumi, Yoshimi; Stotland, Aleksandr; Kim, Brandon J; Huang, Chengqun; Doran, Kelly S; Gottlieb, Roberta A

2016-01-01

Myogenesis is a crucial process governing skeletal muscle development and homeostasis. Differentiation of primitive myoblasts into mature myotubes requires a metabolic switch to support the increased energetic demand of contractile muscle. Skeletal myoblasts specifically shift from a highly glycolytic state to relying predominantly on oxidative phosphorylation (OXPHOS) upon differentiation. We have found that this phenomenon requires dramatic remodeling of the mitochondrial network involving both mitochondrial clearance and biogenesis. During early myogenic differentiation, autophagy is robustly upregulated and this coincides with DNM1L/DRP1 (dynamin 1-like)-mediated fragmentation and subsequent removal of mitochondria via SQSTM1 (sequestosome 1)-mediated mitophagy. Mitochondria are then repopulated via PPARGC1A/PGC-1α (peroxisome proliferator-activated receptor gamma, coactivator 1 alpha)-mediated biogenesis. Mitochondrial fusion protein OPA1 (optic atrophy 1 [autosomal dominant]) is then briskly upregulated, resulting in the reformation of mitochondrial networks. The final product is a myotube replete with new mitochondria. Respirometry reveals that the constituents of these newly established mitochondrial networks are better primed for OXPHOS and are more tightly coupled than those in myoblasts. Additionally, we have found that suppressing autophagy with various inhibitors during differentiation interferes with myogenic differentiation. Together these data highlight the integral role of autophagy and mitophagy in myogenic differentiation.

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.

Feasibility and attractiveness of indication value-based pricing in key EU countries.

PubMed

Flume, Mathias; Bardou, Marc; Capri, Stefano; Sola-Morales, Oriol; Cunningham, David; Levin, Lars-Ake; Touchot, Nicolas

2016-01-01

Indication value-based pricing (IBP) has been proposed in the United States as a tool to capture the differential value of drugs across indications or patient groups and is in the early phases of implementation. In Europe, no major country has experimented with IBP or is seriously discussing its use. We assessed how the reimbursement and pricing environment allows for IBP in seven European countries, evaluating both incentives and hurdles. In price setting countries such as France and Germany, the Health Technology Assessment and pricing process already accounts for differences of value across indications. In countries where differential value drives coverage decisions such as the United Kingdom and Sweden, IBP is likely to be used, at least partially, but not in the short-term. Italy is already achieving some form of differential value through managed entry agreements, whereas in Spain the electronic prescription system provides the infrastructure necessary for IBP but other hurdles exist.

Early host response in the mammary gland after experimental Streptococcus uberis challenge in heifers.

PubMed

de Greeff, Astrid; Zadoks, Ruth; Ruuls, Lisette; Toussaint, Mathilda; Nguyen, Thi Kim Anh; Downing, Alison; Rebel, Johanna; Stockhofe-Zurwieden, Norbert; Smith, Hilde

2013-06-01

Streptococcus uberis is a highly prevalent causative agent of bovine mastitis, which leads to large economic losses in the dairy industry. The aim of this study was to examine the host response during acute inflammation after experimental challenge with capsulated Strep. uberis. Gene expression in response to Strep. uberis was compared between infected and control quarters in 3 animals. All quarters (n=16) were sampled at 16 different locations. Microarray data showed that 239 genes were differentially expressed between infected and control quarters. No differences in gene expression were observed between the different locations. Microarray data were confirmed for several genes using quantitative PCR analysis. Genes differentially expressed due to early Strep. uberis mastitis represented several stages of the process of infection: (1) pathogen recognition; (2) chemoattraction of neutrophils; (3) tissue repair mechanisms; and (4) bactericidal activity. Three different pathogen recognition genes were induced: ficolins, lipopolysaccharide binding protein, and toll-like receptor 2. Calgranulins were found to be the most strongly upregulated genes during early inflammation. By histology and immunohistochemistry, we demonstrated that changes in gene expression in response to Strep. uberis were induced both in infiltrating somatic milk cells and in mammary epithelial cells, demonstrating that the latter cell type plays a role in milk production as well as immune responsiveness. Given the rapid development of inflammation or mastitis after infection, early diagnosis of (Strep. uberis) mastitis is required for prevention of disease and spread of the pathogen. Insight into host responses could help to design immunomodulatory therapies to dampen inflammation after (early) diagnosis of Strep. uberis mastitis. Future research should focus on development of these early diagnostics and immunomodulatory components for mastitis treatment. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Function of FEZF1 during early neural differentiation of human embryonic stem cells.

PubMed

Liu, Xin; Su, Pei; Lu, Lisha; Feng, Zicen; Wang, Hongtao; Zhou, Jiaxi

2018-01-01

The understanding of the mechanism underlying human neural development has been hampered due to lack of a cellular system and complicated ethical issues. Human embryonic stem cells (hESCs) provide an invaluable model for dissecting human development because of unlimited self-renewal and the capacity to differentiate into nearly all cell types in the human body. In this study, using a chemical defined neural induction protocol and molecular profiling, we identified Fez family zinc finger 1 (FEZF1) as a potential regulator of early human neural development. FEZF1 is rapidly up-regulated during neural differentiation in hESCs and expressed before PAX6, a well-established marker of early human neural induction. We generated FEZF1-knockout H1 hESC lines using CRISPR-CAS9 technology and found that depletion of FEZF1 abrogates neural differentiation of hESCs. Moreover, loss of FEZF1 impairs the pluripotency exit of hESCs during neural specification, which partially explains the neural induction defect caused by FEZF1 deletion. However, enforced expression of FEZF1 itself fails to drive neural differentiation in hESCs, suggesting that FEZF1 is necessary but not sufficient for neural differentiation from hESCs. Taken together, our findings identify one of the earliest regulators expressed upon neural induction and provide insight into early neural development in human.

Translational repression by an RNA-binding protein promotes differentiation to infective forms in Trypanosoma cruzi.

PubMed

Romaniuk, Maria Albertina; Frasch, Alberto Carlos; Cassola, Alejandro

2018-06-01

Trypanosomes, protozoan parasites of medical importance, essentially rely on post-transcriptional mechanisms to regulate gene expression in insect vectors and vertebrate hosts. RNA binding proteins (RBPs) that associate to the 3'-UTR of mature mRNAs are thought to orchestrate master developmental programs for these processes to happen. Yet, the molecular mechanisms by which differentiation occurs remain largely unexplored in these human pathogens. Here, we show that ectopic inducible expression of the RBP TcUBP1 promotes the beginning of the differentiation process from non-infective epimastigotes to infective metacyclic trypomastigotes in Trypanosoma cruzi. In early-log epimastigotes TcUBP1 promoted a drop-like phenotype, which is characterized by the presence of metacyclogenesis hallmarks, namely repositioning of the kinetoplast, the expression of an infective-stage virulence factor such as trans-sialidase, increased resistance to lysis by human complement and growth arrest. Furthermore, TcUBP1-ectopic expression in non-infective late-log epimastigotes promoted full development into metacyclic trypomastigotes. TcUBP1-derived metacyclic trypomastigotes were infective in cultured cells, and developed normally into amastigotes in the cytoplasm. By artificial in vivo tethering of TcUBP1 to the 3' untranslated region of a reporter mRNA we were able to determine that translation of the reporter was reduced by 8-fold, while its mRNA abundance was not significantly compromised. Inducible ectopic expression of TcUBP1 confirmed its role as a translational repressor, revealing significant reduction in the translation rate of multiple proteins, a reduction of polysomes, and promoting the formation of mRNA granules. Expression of TcUBP1 truncated forms revealed the requirement of both N and C-terminal glutamine-rich low complexity sequences for the development of the drop-like phenotype in early-log epimastigotes. We propose that a rise in TcUBP1 levels, in synchrony with nutritional deficiency, can promote the differentiation of T. cruzi epimastigotes into infective metacyclic trypomastigotes.

Microarray and differential display identify genes involved in jasmonate-dependent anther development.

PubMed

Mandaokar, Ajin; Kumar, V Dinesh; Amway, Matt; Browse, John

2003-07-01

Jasmonate (JA) is a signaling compound essential for anther development and pollen fertility in Arabidopsis. Mutations that block the pathway of JA synthesis result into male sterility. To understand the processes of anther and pollen maturation, we used microarray and differential display approaches to compare gene expression pattern in anthers of wild-type Arabidopsis and the male-sterile mutant, opr3. Microarray experiment revealed 25 genes that were up-regulated more than 1.8-fold in wild-type anthers as compared to mutant anthers. Experiments based on differential display identified 13 additional genes up-regulated in wild-type anthers compared to opr3 for a total of 38 differentially expressed genes. Searches of the Arabidopsis and non-redundant databases disclosed known or likely functions for 28 of the 38 genes identified, while 10 genes encode proteins of unknown function. Northern blot analysis of eight representative clones as probes confirmed low expression in opr3 anthers compared with wild-type anthers. JA responsiveness of these same genes was also investigated by northern blot analysis of anther RNA isolated from wild-type and opr3 plants, In these experiments, four genes were induced in opr3 anthers within 0.5-1 h of JA treatment while the remaining genes were up-regulated only 1-8 h after JA application. None of these genes was induced by JA in anthers of the coil mutant that is deficient in JA responsiveness. The four early-induced genes in opr3 encode lipoxygenase, a putative bHLH transcription factor, epithiospecifier protein and an unknown protein. We propose that these and other early components may be involved in JA signaling and in the initiation of developmental processes. The four late genes encode an extensin-like protein, a peptide transporter and two unknown proteins, which may represent components required later in anther and pollen maturation. Transcript profiling has provided a successful approach to identify genes involved in anther and pollen maturation in Arabidopsis.

Early events in xenograft development from the human embryonic stem cell line HS181--resemblance with an initial multiple epiblast formation.

PubMed

Gertow, Karin; Cedervall, Jessica; Jamil, Seema; Ali, Rouknuddin; Imreh, Marta P; Gulyas, Miklos; Sandstedt, Bengt; Ahrlund-Richter, Lars

2011-01-01

Xenografting is widely used for assessing in vivo pluripotency of human stem cell populations. Here, we report on early to late events in the development of mature experimental teratoma from a well-characterized human embryonic stem cell (HESC) line, HS181. The results show an embryonic process, increasingly chaotic. Active proliferation of the stem cell derived cellular progeny was detected already at day 5, and characterized by the appearance of multiple sites of engraftment, with structures of single or pseudostratified columnar epithelium surrounding small cavities. The striking histological resemblance to developing embryonic ectoderm, and the formation of epiblast-like structures was supported by the expression of the markers OCT4, NANOG, SSEA-4 and KLF4, but a lack of REX1. The early neural marker NESTIN was uniformly expressed, while markers linked to gastrulation, such as BMP-4, NODAL or BRACHYURY were not detected. Thus, observations on day 5 indicated differentiation comparable to the most early transient cell populations in human post implantation development. Confirming and expanding on previous findings from HS181 xenografts, these early events were followed by an increasingly chaotic development, incorporated in the formation of a benign teratoma with complex embryonic components. In the mature HS181 teratomas not all types of organs/tissues were detected, indicating a restricted differentiation, and a lack of adequate spatial developmental cues during the further teratoma formation. Uniquely, a kinetic alignment of rare complex structures was made to human embryos at diagnosed gestation stages, showing minor kinetic deviations between HS181 teratoma and the human counterpart.

Evolutionary radiation of "stone plants" in the genus Argyroderma (Aizoaceae): unraveling the effects of landscape, habitat, and flowering time.

PubMed

Ellis, Allan G; Weis, Arthur E; Gaut, Brandon S

2006-01-01

Recent phylogenetic evidence suggests that the extraordinary diversity of the Cape Floristic Kingdom in South Africa may be the result of widespread evolutionary radiation. Our understanding of the role of adaptive versus neutral processes in these radiations remains largely speculative. In this study we investigated factors involved in the diversification of Argyroderma, a genus within the most spectacular of the Cape radiations, that of the Ruschioid subfamily of the Aizoaceae. We used amplified fragment length polymorphisms and a suite of morphological traits to elucidate patterns of differentiation within and between species of Argyroderma across the range of the genus. We then used a matrix correlation approach to assess the influence of landscape structure, edaphic gradients, and flowering phenology on phenotypic and neutral genetic divergence in the system. We found evidence for strong spatial genetic isolation at all taxonomic levels. In addition, genetic differentiation occurs along a temporal axis, between sympatric species with divergent flowering times. Morphological differentiation, which previous studies suggest is adaptive, occurs along a habitat axis, between populations occupying different edaphic microenvironments. Morphological differentiation is in turn significantly associated with flowering time shifts. Thus we propose that diversification within Argyroderma has occurred through a process of adaptive speciation in allopatry. Spatially isolated populations diverge phenotypically in response to divergent habitat selection, which in turn leads to the evolution of reproductive isolation through divergence of flowering phenologies, perhaps as a correlated response to morphological divergence. Evidence suggests that diversification of the group has proceeded in two phases: the first involving divergence of allopatric taxa on varied microhabitats within a novel habitat type (the quartz gravel plains), and the second involving range expansion of an early flowering phenotype on the most extreme edaphic habitat and subsequent incomplete differentiation of allopatric populations of the early flowering group. These results point to adaptive speciation in allopatry as a likely model for the spectacular diversification of the ice-plant family in the dissected landscapes of the southern African winter rainfall deserts.

Gene expression profiling of mesenteric lymph nodes from sheep with natural scrapie

PubMed Central

2014-01-01

Background Prion diseases are characterized by the accumulation of the pathogenic PrPSc protein, mainly in the brain and the lymphoreticular system. Although prions multiply/accumulate in the lymph nodes without any detectable pathology, transcriptional changes in this tissue may reflect biological processes that contribute to the molecular pathogenesis of prion diseases. Little is known about the molecular processes that occur in the lymphoreticular system in early and late stages of prion disease. We performed a microarray-based study to identify genes that are differentially expressed at different disease stages in the mesenteric lymph node of sheep naturally infected with scrapie. Oligo DNA microarrays were used to identify gene-expression profiles in the early/middle (preclinical) and late (clinical) stages of the disease. Results In the clinical stage of the disease, we detected 105 genes that were differentially expressed (≥2-fold change in expression). Of these, 43 were upregulated and 62 downregulated as compared with age-matched negative controls. Fewer genes (50) were differentially expressed in the preclinical stage of the disease. Gene Ontology enrichment analysis revealed that the differentially expressed genes were largely associated with the following terms: glycoprotein, extracellular region, disulfide bond, cell cycle and extracellular matrix. Moreover, some of the annotated genes could be grouped into 3 specific signaling pathways: focal adhesion, PPAR signaling and ECM-receptor interaction. We discuss the relationship between the observed gene expression profiles and PrPSc deposition and the potential involvement in the pathogenesis of scrapie of 7 specific differentially expressed genes whose expression levels were confirmed by real time-PCR. Conclusions The present findings identify new genes that may be involved in the pathogenesis of natural scrapie infection in the lymphoreticular system, and confirm previous reports describing scrapie-induced alterations in the expression of genes involved in protein misfolding, angiogenesis and the oxidative stress response. Further studies will be necessary to determine the role of these genes in prion replication, dissemination and in the response of the organism to this disease. PMID:24450868

Isolation and Functional Characterization of Two Distinct Sexual-Stage-Specific Promoters of the Human Malaria Parasite Plasmodium falciparum†

PubMed Central

Dechering, Koen J.; Kaan, Anita M.; Mbacham, Wilfred; Wirth, Dyann F.; Eling, Wijnand; Konings, Ruud N. H.; Stunnenberg, Hendrik G.

1999-01-01

Transmission of malaria depends on the successful development of the sexual stages of the parasite within the midgut of the mosquito vector. The differentiation process leading to the production of the sexual stages is delineated by several developmental switches. Arresting the progression through this sexual differentiation pathway would effectively block the spread of the disease. The successful development of such transmission-blocking agents is hampered by the lack of a detailed understanding of the program of gene expression that governs sexual differentiation of the parasite. Here we describe the isolation and functional characterization of the Plasmodium falciparum pfs16 and pfs25 promoters, whose activation marks the developmental switches executed during the sexual differentiation process. We have studied the differential activation of the pfs16 and pfs25 promoters during intraerythrocytic development by transfection of P. falciparum and during gametogenesis and early sporogonic development by transfection of the related malarial parasite P. gallinaceum. Our data indicate that the promoter of the pfs16 gene is activated at the onset of gametocytogenesis, while the activity of the pfs25 promoter is induced following the transition to the mosquito vector. Both promoters have unusual DNA compositions and are extremely A/T rich. We have identified the regions in the pfs16 and pfs25 promoters that are essential for high transcriptional activity. Furthermore, we have identified a DNA-binding protein, termed PAF-1, which activates pfs25 transcription in the mosquito midgut. The data presented here shed the first light on the details of processes of gene regulation in the important human pathogen P. falciparum. PMID:9891033

Discriminating male and female voices: differentiating pitch and gender.

PubMed

Latinus, Marianne; Taylor, Margot J

2012-04-01

Gender is salient, socially critical information obtained from faces and voices, yet the brain processes underlying gender discrimination have not been well studied. We investigated neural correlates of gender processing of voices in two ERP studies. In the first, ERP differences were seen between female and male voices starting at 87 ms, in both spatial-temporal and peak analyses, particularly the fronto-central N1 and P2. As pitch differences may drive gender differences, the second study used normal, high- and low-pitch voices. The results of these studies suggested that differences in pitch produced early effects (27-63 ms). Gender effects were seen on N1 (120 ms) with implicit pitch processing (study 1), but were not seen with manipulations of pitch (study 2), demonstrating that N1 was modulated by attention. P2 (between 170 and 230 ms) discriminated male from female voices, independent of pitch. Thus, these data show that there are two stages in voice gender processing; a very early pitch or frequency discrimination and a later more accurate determination of gender at the P2 latency.

Forsterite/melt partitioning of argon and iodine: Implications for atmosphere formation by outgassing of an early Martian magma ocean

NASA Technical Reports Server (NTRS)

Musselwhite, Donald S.; Drake, Michael J.; Swindle, Timothy D.

1992-01-01

Argon and Xe in the Martian atmosphere are radiogenic relative to the Martian mantle if the SNC meteorites are from Mars. Decay of the short lived isotope I-129 to Xe-129 (t sub 1/2 = 16 m.y.) is the most plausible source of the radiogenic Xe. This short half life constrains any process responsible for the elevated Xe-129/Xe-132 ratio of the Martian atmosphere to occur very early in solar system history. Musselwhite et al. proposed that the differential solubility of I and Xe in liquid water played a key role in producing the radiogenic signature in the Martian atmosphere. Here we explore an alternative hypothesis involving purely igneous processes, and motivated in part by new experimental results on the partitioning of I and Xe between minerals and melt.

Strategies for Investigating Early Mars Using Returned Samples

NASA Technical Reports Server (NTRS)

Carrier, B. L.; Beaty, D. W.; McSween, H. Y.; Czaja, A. D.; Goreva, Y. S.; Hausrath, E. M.; Herd, C. D. K.; Humayun, M.; McCubbin, F. M.; McLennan, S. M.;

Comparative Analysis of Mouse-Induced Pluripotent Stem Cells and Mesenchymal Stem Cells During Osteogenic Differentiation In Vitro

PubMed Central

Kayashima, Hiroki; Miura, Jiro; Uraguchi, Shinya; Wang, Fangfang; Okawa, Hiroko; Sasaki, Jun-Ichi; Saeki, Makio; Matsumoto, Takuya; Yatani, Hirofumi

2014-01-01

Induced pluripotent stem cells (iPSCs) can differentiate into mineralizing cells and are, therefore, expected to be useful for bone regenerative medicine; however, the characteristics of iPSC-derived osteogenic cells remain unclear. Here, we provide a direct in vitro comparison of the osteogenic differentiation process in mesenchymal stem cells (MSCs) and iPSCs from adult C57BL/6J mice. After 30 days of culture in osteogenic medium, both MSCs and iPSCs produced robustly mineralized bone nodules that contained abundant calcium phosphate with hydroxyapatite crystal formation. Mineral deposition was significantly higher in iPSC cultures than in MSC cultures. Scanning electron microscopy revealed budding matrix vesicles in early osteogenic iPSCs; subsequently, the vesicles propagated to exhibit robust mineralization without rich fibrous structures. Early osteogenic MSCs showed deposition of many matrix vesicles in abundant collagen fibrils that became solid mineralized structures. Both cell types demonstrated increased expression of osteogenic marker genes, such as runx2, osterix, dlx5, bone sialoprotein (BSP), and osteocalcin, during osteogenesis; however, real-time reverse transcription–polymerase chain reaction array analysis revealed that osteogenesis-related genes encoding mineralization-associated molecules, bone morphogenetic proteins, and extracellular matrix collagens were differentially expressed between iPSCs and MSCs. These data suggest that iPSCs are capable of differentiation into mature osteoblasts whose associated hydroxyapatite has a crystal structure similar to that of MSC-associated hydroxyapatite; however, the transcriptional differences between iPSCs and MSCs could result in differences in the mineral and matrix environments of the bone nodules. Determining the biological mechanisms underlying cell-specific differences in mineralization during in vitro iPSC osteogenesis may facilitate the development of clinically effective engineered bone. PMID:24625139

Pregnancy-Related Coronary Artery Dissection: Recognition of a Life Threatening Process.

PubMed

Robinson, Julie R

Pregnancy-related spontaneous coronary artery dissection (P-SCAD) is a rare but life-threatening condition of the peripartum and postpartum mother. The gold standard of diagnosing P-SCAD is a left cardiac catheterization; however, this diagnostic tool may not be used early because myocardial infarction is not typically a top differential diagnosis for women and especially young pregnant women presenting with acute chest pain. Providers and registered nurses, particularly those in the prehospital setting, the emergency department, and labor and delivery units, should be aware of signs, symptoms, potential risk factors, and diagnostic results that could indicate P-SCAD and initiate early and appropriate treatment to improve maternal outcomes.

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.

Klf10 regulates odontoblast differentiation and mineralization via promoting expression of dentin matrix protein 1 and dentin sialophosphoprotein genes

PubMed Central

Chen, Zhuo; Li, Wentong; Wang, Han; Wan, Chunyan; Luo, Daoshu; Deng, Shuli

2016-01-01

Klf10, a member of the Krüppel-like family of transcription factors, is critical for osteoblast differentiation, bone formation and mineralization. However, whether Klf10 is involved in odontoblastic differentiation and tooth development has not been determined. In this study, we investigate the expression patterns of Klf10 during murine tooth development in vivo and its role in odontoblastic differentiation in vitro. Klf10 protein was expressed in the enamel organ and the underlying mesenchyme, ameloblasts and odontoblasts at early and later stages of murine molar formation. Furthermore, the expression of Klf10, Dmp1, Dspp and Runx2 was significantly elevated during the process of mouse dental papilla mesenchymal differentiation and mineralization. The overexpression of Klf10 induced dental papilla mesenchymal cell differentiation and mineralization as detected by alkaline phosphatase staining and alizarin red S assay. Klf10 additionally up-regulated the expression of odontoblastic differentiation marker genes Dmp1, Dspp and Runx2 in mouse dental papilla mesenchymal cells. The molecular mechanism of Klf10 in controlling Dmp1 and Dspp expression is thus to activate their regulatory regions in a dosage-dependent manner. Our results suggest that Klf10 is involved in tooth development and promotes odontoblastic differentiation via the up-regulation of Dmp1 and Dspp transcription. PMID:26310138

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.

Development of Children at Risk for Adverse Outcomes Participating in Early Intervention in Developing Countries: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Wallander, Jan L.; Bann, Carla M.; Biasini, Fred J.; Goudar, Shivaprasad S.; Pasha, Omrana; Chomba, Elwyn; McClure, Elizabeth; Carlo, Waldemar A.

2014-01-01

Background: Previous research has indicated positive effects of early developmental intervention (EDI) on the development of children in developing countries. Few studies, however, have examined longitudinally when differential treatment effects may be observed and whether differential outcomes are associated with exposure to different risk…

Sex Differential Item Functioning in the Inventory of Early Development III Social-Emotional Skills

ERIC Educational Resources Information Center

Beaver, Jessica L.; French, Brian F.; Finch, W. Holmes; Ullrich-French, Sarah C.

2014-01-01

Social-emotional (SE) skills in the early developmental years of children influence outcomes in psychological, behavioral, and learning domains. The adult ratings of a child's SE skills can be influenced by sex stereotypes. These rating differences could lead to differential conclusions about developmental progress or risk. To ensure that…

Do Guilt- and Shame-Proneness Differentially Predict Prosocial, Aggressive, and Withdrawn Behaviors during Early Adolescence?

ERIC Educational Resources Information Center

Roos, Sanna; Hodges, Ernest V. E.; Salmivalli, Christina

2014-01-01

In this short-term longitudinal study, we systematically examined the distinctiveness of guilt- and shame-proneness in early adolescents (N = 395, mean age = 11.8 years) in terms of differential relations with peer reported prosocial behavior, withdrawal, and aggression. Results from structural equation modeling indicated that guilt-proneness…

EGR-1 Expression in Catecholamine-synthesizing Neurons Reflects Auditory Learning and Correlates with Responses in Auditory Processing Areas.

PubMed

Dai, Jennifer B; Chen, Yining; Sakata, Jon T

2018-05-21

Distinguishing between familiar and unfamiliar individuals is an important task that shapes the expression of social behavior. As such, identifying the neural populations involved in processing and learning the sensory attributes of individuals is important for understanding mechanisms of behavior. Catecholamine-synthesizing neurons have been implicated in sensory processing, but relatively little is known about their contribution to auditory learning and processing across various vertebrate taxa. Here we investigated the extent to which immediate early gene expression in catecholaminergic circuitry reflects information about the familiarity of social signals and predicts immediate early gene expression in sensory processing areas in songbirds. We found that male zebra finches readily learned to differentiate between familiar and unfamiliar acoustic signals ('songs') and that playback of familiar songs led to fewer catecholaminergic neurons in the locus coeruleus (but not in the ventral tegmental area, substantia nigra, or periaqueductal gray) expressing the immediate early gene, EGR-1, than playback of unfamiliar songs. The pattern of EGR-1 expression in the locus coeruleus was similar to that observed in two auditory processing areas implicated in auditory learning and memory, namely the caudomedial nidopallium (NCM) and the caudal medial mesopallium (CMM), suggesting a contribution of catecholamines to sensory processing. Consistent with this, the pattern of catecholaminergic innervation onto auditory neurons co-varied with the degree to which song playback affected the relative intensity of EGR-1 expression. Together, our data support the contention that catecholamines like norepinephrine contribute to social recognition and the processing of social information. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Biomarker Discovery for Early Detection of Hepatocellular Carcinoma in Hepatitis C–infected Patients*

PubMed Central

Mustafa, Mehnaz G.; Petersen, John R.; Ju, Hyunsu; Cicalese, Luca; Snyder, Ned; Haidacher, Sigmund J.; Denner, Larry; Elferink, Cornelis

2013-01-01

Chronic hepatic disease damages the liver, and the resulting wound-healing process leads to liver fibrosis and the subsequent development of cirrhosis. The leading cause of hepatic fibrosis and cirrhosis is infection with hepatitis C virus (HCV), and of the patients with HCV-induced cirrhosis, 2% to 5% develop hepatocellular carcinoma (HCC), with a survival rate of 7%. HCC is one of the leading causes of cancer-related death worldwide, and the poor survival rate is largely due to late-stage diagnosis, which makes successful intervention difficult, if not impossible. The lack of sensitive and specific diagnostic tools and the urgent need for early-stage diagnosis prompted us to discover new candidate biomarkers for HCV and HCC. We used aptamer-based fractionation technology to reduce serum complexity, differentially labeled samples (six HCV and six HCC) with fluorescent dyes, and resolved proteins in pairwise two-dimensional difference gel electrophoresis. DeCyder software was used to identify differentially expressed proteins and spots picked, and MALDI-MS/MS was used to determine that ApoA1 was down-regulated by 22% (p < 0.004) in HCC relative to HCV. Differential expression quantified via two-dimensional difference gel electrophoresis was confirmed by means of 18O/16O stable isotope differential labeling with LC-MS/MS zoom scans. Technically independent confirmation was demonstrated by triple quadrupole LC-MS/MS selected reaction monitoring (SRM) assays with three peptides specific to human ApoA1 (DLATVYVDVLK, WQEEMELYR, and VSFLSALEEYTK) using 18O/16O-labeled samples and further verified with AQUA peptides as internal standards for quantification. In 50 patient samples (24 HCV and 26 HCC), all three SRM assays yielded highly similar differential expression of ApoA1 in HCC and HCV patients. These results validated the SRM assays, which were independently confirmed by Western blotting. Thus, ApoA1 is a candidate member of an SRM biomarker panel for early diagnosis, prognosis, and monitoring of HCC. Future multiplexing of SRM assays for other candidate biomarkers is envisioned to develop a biomarker panel for subsequent verification and validation studies. PMID:24008390

Bulk Composition of Vesta as Constrained by the Dawn Mission and the HED Meteorites

NASA Technical Reports Server (NTRS)

Toplis, M. J.; Mizzon, H.; Forni, O.; Monnereau, H.; Prettyman, T. H.; McSween, H. Y.; McCoy, T. J.; Mittlefehldt, D. W.; DeSactis, M. C.; Raymond, C. T.;

Low-frequency repetitive transcranial magnetic stimulation (rTMS) affects event-related potential measures of novelty processing in autism.

PubMed

Sokhadze, Estate; Baruth, Joshua; Tasman, Allan; Mansoor, Mehreen; Ramaswamy, Rajesh; Sears, Lonnie; Mathai, Grace; El-Baz, Ayman; Casanova, Manuel F

2010-06-01

In our previous study on individuals with autism spectrum disorder (ASD) (Sokhadze et al., Appl Psychophysiol Biofeedback 34:37-51, 2009a) we reported abnormalities in the attention-orienting frontal event-related potentials (ERP) and the sustained-attention centro-parietal ERPs in a visual oddball experiment. These results suggest that individuals with autism over-process information needed for the successful differentiation of target and novel stimuli. In the present study we examine the effects of low-frequency, repetitive Transcranial Magnetic Stimulation (rTMS) on novelty processing as well as behavior and social functioning in 13 individuals with ASD. Our hypothesis was that low-frequency rTMS application to dorsolateral prefrontal cortex (DLFPC) would result in an alteration of the cortical excitatory/inhibitory balance through the activation of inhibitory GABAergic double bouquet interneurons. We expected to find post-TMS differences in amplitude and latency of early and late ERP components. The results of our current study validate the use of low-frequency rTMS as a modulatory tool that altered the disrupted ratio of cortical excitation to inhibition in autism. After rTMS the parieto-occipital P50 amplitude decreased to novel distracters but not to targets; also the amplitude and latency to targets increased for the frontal P50 while decreasing to non-target stimuli. Low-frequency rTMS minimized early cortical responses to irrelevant stimuli and increased responses to relevant stimuli. Improved selectivity in early cortical responses lead to better stimulus differentiation at later-stage responses as was made evident by our P3b and P3a component findings. These results indicate a significant change in early, middle-latency and late ERP components at the frontal, centro-parietal, and parieto-occipital regions of interest in response to target and distracter stimuli as a result of rTMS treatment. Overall, our preliminary results show that rTMS may prove to be an important research tool or treatment modality in addressing the stimulus hypersensitivity characteristic of autism spectrum disorders.

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

Evaluation of genetic variability among "Early Mature" Juglans regia using microsatellite markers and morphological traits.

PubMed

Ebrahimi, Aziz; Zarei, Abdolkarim; Zamani Fardadonbeh, Mojtaba; Lawson, Shaneka

2017-01-01

Limiting the juvenile phase and reducing tree size are the two main challenges for breeders to improve most fruit crops. Early maturation and dwarf cultivars have been reported for many fruit species. "Early mature" and low vigor walnut genotypes were found among seedlings of Persian walnut. Nine microsatellite markers were used to evaluate genetic diversity among "Early Mature" Persian walnut accessions and provide a comparison with "normal growth" accessions. Six maturation related characteristics were also measured in "Early Mature" samples. Phenotypic traits and diversity indices showed relatively high levels of genetic diversity in "Early Mature" seedlings and indicated high differentiation between individuals. Seedling height, the most diverse phenotypic trait, has an important role in the clustering of "Early Mature" accessions. The "Early Mature" type had higher number of alleles, number of effective allele, and Shannon index compared to the "Normal Growth" group. The two types of studied walnuts had different alleles, with more than half of produced alleles specific to a specific group. "Early Mature" and "Normal Growth" walnuts had 27 and 17 private alleles, respectively. Grouping with different methods separated "Early Mature" and "Normal Growth" samples entirely. The presence of moderate to high genetic diversity in "Early Mature" walnuts and high genetic differentiation with "Normal Growth" walnuts, indicated that "Early Mature" walnuts were more diverse and distinct from "Normal Growth" samples. Moreover, our results showed SSR markers were useful for differentiating between "Early Mature" and "Normal Growth" walnuts. A number of identified loci have potential in breeding programs for identification of "Early Mature" walnuts at the germination phase.

Formononetin promotes early fracture healing through stimulating angiogenesis by up-regulating VEGFR-2/Flk-1 in a rat fracture model.

PubMed

Huh, Jeong-Eun; Kwon, Na-Hyun; Baek, Young-Hyun; Lee, Jae-Dong; Choi, Do-Young; Jingushi, Seiya; Kim, Kang-il; Park, Dong-Suk

2009-11-01

Plant-derived phytoestrogens have bone protective effects, but the molecular mechanism behind these effects remains unclear. This study is aimed at fully characterizing the fracture healing process of formononetin, and investigating the mechanism underlying angiogenesis in calluses of a rat fracture model. Femoral fractures were produced in 2-month-old Sprague-Dawley rats. A 20 microg/kg or 200 microg/kg dose of formononetin was orally administrated once a day during the healing period of 21 days. The results showed that in the early stage of chondrogenesis (days 3), formononetin significantly increased the number of vessels, and expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2/flk-1) compared with control. However, the larger dose of formononetin had no significant difference on expression of VEGF and VEGFR-2/Flk-1 compared with that of the smaller dose of formononetin. After 7 days of administration, formononetin markedly induced differentiation of mesenchymal stem cells in the fracture site. After 14 days, gene expression of mesenchymal progenitors such as alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN) and collagen type I (Col I), indicating osteogenic differentiation, was markedly stimulated by formononetin compared with control. These results suggest that formononetin promotes early fracture healing through angiogenesis activation in the early stage of fracture repair, and osteogenesis acceleration in the later stages, and thus may be beneficial for fracture healing.

Differential roles of glucosinolates and camalexin at different stages of Agrobacterium-mediated transformation.

PubMed

Shih, Po-Yuan; Chou, Shu-Jen; Müller, Caroline; Halkier, Barbara Ann; Deeken, Rosalia; Lai, Erh-Min

2018-03-02

Agrobacterium tumefaciens is the causal agent of crown gall disease in a wide range of plants via a unique interkingdom DNA transfer from bacterial cells into the plant genome. Agrobacterium tumefaciens is capable of transferring its T-DNA into different plant parts at different developmental stages for transient and stable transformation. However, the plant genes and mechanisms involved in these transformation processes are not well understood. We used Arabidopsis thaliana Col-0 seedlings to reveal the gene expression profiles at early time points during Agrobacterium infection. Common and differentially expressed genes were found in shoots and roots. A gene ontology analysis showed that the glucosinolate (GS) biosynthesis pathway was an enriched common response. Strikingly, several genes involved in indole glucosinolate (iGS) modification and the camalexin biosynthesis pathway were up-regulated, whereas genes in aliphatic glucosinolate (aGS) biosynthesis were generally down-regulated, on Agrobacterium infection. Thus, we evaluated the impacts of GSs and camalexin during different stages of Agrobacterium-mediated transformation combining Arabidopsis mutant studies, metabolite profiling and exogenous applications of various GS hydrolysis products or camalexin. The results suggest that the iGS hydrolysis pathway plays an inhibitory role on transformation efficiency in Arabidopsis seedlings at the early infection stage. Later in the Agrobacterium infection process, the accumulation of camalexin is a key factor inhibiting tumour development on Arabidopsis inflorescence stalks. In conclusion, this study reveals the differential roles of GSs and camalexin at different stages of Agrobacterium-mediated transformation and provides new insights into crown gall disease control and improvement of plant transformation. © 2018 THE AUTHORS. MOLECULAR PLANT PATHOLOGY PUBLISHED BY BRITISH SOCIETY FOR PLANT PATHOLOGY AND JOHN WILEY & SONS LTD.

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.

Origin of the lunar highlands Mg-suite: An integrated petrology, geochemistry, chronology, and remote sensing perspective

DOE PAGES

Shearer, C. K.; Elardo, S. M.; Petro, N. E.; ...

2014-12-23

The Mg-suite represents an enigmatic episode of lunar highlands magmatism that presumably represents the first stage of crustal building following primordial differentiation. This review examines the mineralogy, geochemistry, petrology, chronology, and the planetary-scale distribution of this suite of highlands plutonic rocks, presents models for their origin, examines petrogenetic relationships to other highlands rocks, and explores the link between this style of magmatism and early stages of lunar differentiation. Of the models considered for the origin of the parent magmas for the Mg-suite, the data best fit a process in which hot (solidus temperature at ≥2 GPa = 1600 to 1800more » °C) and less dense (r ~3100 kg/m3) early lunar magma ocean cumulates rise to the base of the crust during cumulate pile overturn. Some decompressional melting would occur, but placing a hot cumulate horizon adjacent to the plagioclase-rich primordial crust and KREEP-rich lithologies (at temperatures of <1300 °C) would result in the hybridization of these divergent primordial lithologies, producing Mg-suite parent magmas. As urKREEP (primeval KREEP) is not the “petrologic driver” of this style of magmatism, outside of the Procellarum KREEP Terrane (PKT), Mg-suite magmas are not required to have a KREEP signature. Evaluation of the chronology of this episode of highlands evolution indicates that Mg-suite magmatism was initiated soon after primordial differentiation (<10 m.y.). Alternatively, the thermal event associated with the mantle overturn may have disrupted the chronometers utilized to date the primordial crust. Petrogenetic relationships between the Mg-suite and other highlands suites (e.g., alkali-suite and magnesian anorthositic granulites) are consistent with both fractional crystallization processes and melting of distinctly different hybrid sources.« less

Early inner solar system origin for anomalous sulfur isotopes in differentiated protoplanets.

PubMed

Antonelli, Michael A; Kim, Sang-Tae; Peters, Marc; Labidi, Jabrane; Cartigny, Pierre; Walker, Richard J; Lyons, James R; Hoek, Joost; Farquhar, James

2014-12-16

Achondrite meteorites have anomalous enrichments in (33)S, relative to chondrites, which have been attributed to photochemistry in the solar nebula. However, the putative photochemical reactions remain elusive, and predicted accompanying (33)S depletions have not previously been found, which could indicate an erroneous assumption regarding the origins of the (33)S anomalies, or of the bulk solar system S-isotope composition. Here, we report well-resolved anomalous (33)S depletions in IIIF iron meteorites (<-0.02 per mil), and (33)S enrichments in other magmatic iron meteorite groups. The (33)S depletions support the idea that differentiated planetesimals inherited sulfur that was photochemically derived from gases in the early inner solar system (<∼2 AU), and that bulk inner solar system S-isotope composition was chondritic (consistent with IAB iron meteorites, Earth, Moon, and Mars). The range of mass-independent sulfur isotope compositions may reflect spatial or temporal changes influenced by photochemical processes. A tentative correlation between S isotopes and Hf-W core segregation ages suggests that the two systems may be influenced by common factors, such as nebular location and volatile content.

Identification of differentially expressed genes in the oviduct of two rabbit lines divergently selected for uterine capacity using suppression subtractive hybridization.

PubMed

Ballester, M; Castelló, A; Peiró, R; Argente, M J; Santacreu, M A; Folch, J M

2013-06-01

Suppressive subtractive hybridization libraries from oviduct at 62 h post-mating of two lines of rabbits divergently selected for uterine capacity were generated to identify differentially expressed genes. A total of 438 singletons and 126 contigs were obtained by cluster assembly and sequence alignment of 704 expressed sequence tags (ESTs), of which 54% showed homology to known proteins of the non-redundant NCBI databases. Differential screening by dot blot validated 71 ESTs, of which 47 showed similarity to known genes. Transcripts of genes were functionally annotated in the molecular function and the biological process gene ontology categories using the BLAST2GO software and were assigned to reproductive developmental process, immune response, amino acid metabolism and degradation, response to stress and apoptosis terms. Finally, three interesting genes, PGR, HSD17B4 and ERO1L, were identified as overexpressed in the low line using RT-qPCR. Our study provides a list of candidate genes that can be useful to understanding the molecular mechanisms underlying the phenotypic differences observed in early embryo survival and development traits. © 2012 The Authors, Animal Genetics © 2012 Stichting International Foundation for Animal Genetics.

Role for early-differentiated natural killer cells in infectious mononucleosis

PubMed Central

Azzi, Tarik; Lünemann, Anna; Murer, Anita; Ueda, Seigo; Béziat, Vivien; Malmberg, Karl-Johan; Staubli, Georg; Gysin, Claudine; Berger, Christoph; Münz, Christian

2014-01-01

A growing body of evidence suggests that the human natural killer (NK)-cell compartment is phenotypically and functionally heterogeneous and is composed of several differentiation stages. Moreover, NK-cell subsets have been shown to exhibit adaptive immune features during herpes virus infection in experimental mice and to expand preferentially during viral infections in humans. However, both phenotype and role of NK cells during acute symptomatic Epstein-Barr virus (EBV) infection, termed infectious mononucleosis (IM), remain unclear. Here, we longitudinally assessed the kinetics, the differentiation, and the proliferation of subsets of NK cells in pediatric IM patients. Our results indicate that acute IM is characterized by the preferential proliferation of early-differentiated CD56dim NKG2A+ immunoglobulin-like receptor- NK cells. Moreover, this NK-cell subset exhibits features of terminal differentiation and persists at higher frequency during at least the first 6 months after acute IM. Finally, we demonstrate that this NK-cell subset preferentially degranulates and proliferates on exposure to EBV-infected B cells expressing lytic antigens. Thus, early-differentiated NK cells might play a key role in the immune control of primary infection with this persistent tumor-associated virus. PMID:25205117

Role for early-differentiated natural killer cells in infectious mononucleosis.

PubMed

Azzi, Tarik; Lünemann, Anna; Murer, Anita; Ueda, Seigo; Béziat, Vivien; Malmberg, Karl-Johan; Staubli, Georg; Gysin, Claudine; Berger, Christoph; Münz, Christian; Chijioke, Obinna; Nadal, David

2014-10-16

A growing body of evidence suggests that the human natural killer (NK)-cell compartment is phenotypically and functionally heterogeneous and is composed of several differentiation stages. Moreover, NK-cell subsets have been shown to exhibit adaptive immune features during herpes virus infection in experimental mice and to expand preferentially during viral infections in humans. However, both phenotype and role of NK cells during acute symptomatic Epstein-Barr virus (EBV) infection, termed infectious mononucleosis (IM), remain unclear. Here, we longitudinally assessed the kinetics, the differentiation, and the proliferation of subsets of NK cells in pediatric IM patients. Our results indicate that acute IM is characterized by the preferential proliferation of early-differentiated CD56(dim) NKG2A(+) immunoglobulin-like receptor(-) NK cells. Moreover, this NK-cell subset exhibits features of terminal differentiation and persists at higher frequency during at least the first 6 months after acute IM. Finally, we demonstrate that this NK-cell subset preferentially degranulates and proliferates on exposure to EBV-infected B cells expressing lytic antigens. Thus, early-differentiated NK cells might play a key role in the immune control of primary infection with this persistent tumor-associated virus. © 2014 by The American Society of Hematology.

Floral Initiation in Response to Planting Date Reveals the Key Role of Floral Meristem Differentiation Prior to Budding in Canola (Brassica napus L.).

PubMed

Zhang, Yaofeng; Zhang, Dongqing; Yu, Huasheng; Lin, Baogang; Fu, Ying; Hua, Shuijin

2016-01-01

In Brassica napus, floral development is a decisive factor in silique formation, and it is influenced by many cultivation practices including planting date. However, the effect of planting date on floral initiation in canola is poorly understood at present. A field experiment was conducted using a split plot design, in which three planting dates (early, 15 September, middle, 1 October, and late, 15 October) served as main plot and five varieties differing in maturity (1358, J22, Zhongshuang 11, Zheshuang 8, and Zheyou 50) employed as subplot. The purpose of this study was to shed light on the process of floral meristem (FM) differentiation, the influence of planting date on growth period (GP) and floral initiation, and silique formation. The main stages of FM developments can be divided into four stages: first, the transition from shoot apical meristem to FM; second, flower initiation; third, gynoecium and androecium differentiation; and fourth, bud formation. Our results showed that all genotypes had increased GPs from sowing to FM differentiation as planting date was delayed while the GPs from FM differentiation to budding varied year by year except the very early variety, 1358. Based on the number of flowers present at the different reproductive stages, the flowers produced from FM differentiation to budding closely approximated the final silique even though the FM differentiated continuously after budding and peaked generally at the middle flowering stage. The ratio of siliques to maximum flower number ranged from 48 to 80%. These results suggest that (1) the period from FM differentiation to budding is vital for effective flower and silique formation although there was no significant correlation between the length of the period and effective flowers and siliques, and (2) the increased number of flowers from budding were generally ineffective. Therefore, maximizing flower numbers prior to budding will improve silique numbers, and reducing FM degeneration should also increase final silique formation. From the results of our study, we offer guidelines for planting canola varieties that differ in maturity in order to maximize effective flower numbers.

ING4 Loss in Prostate Cancer Progression

DTIC Science & Technology

2016-10-01

proper transitioning from late stage pregnancy to early lactation [12]. ING4 expres- sion is also lost in some breast cancers [13] where it may suppress...differentiation, Pten is elevated early (Fig. 6a), but decreases after ING4 is induced and CREB becomes active (after day 10). In EMP cells, CREB/ATF1 is...constitutive CREB/ATF1 activation (Fig. 6c) as early as 4 days after differentiation, before it is detected in normal PrECs. We observed a

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.

High Efficient Differentiation of Functional Hepatocytes from Porcine Induced Pluripotent Stem Cells

PubMed Central

Ao, Ying; Mich-Basso, Jocelyn Danielle; Lin, Bo; Yang, Lei

2014-01-01

Hepatocyte transplantation is considered to be a promising therapy for patients with liver diseases. Induced pluripotent stem cells (iPSCs) provide an unlimited source for the generation of functional hepatocytes. In this study, we generated iPSCs from porcine ear fibroblasts (PEFs) by overexpressing Sox2, Klf4, Oct4, and c-Myc (SKOM), and developed a novel strategy for the efficient differentiation of hepatocyte-like cells from porcine iPSCs by following the processes of early liver development. The differentiated cells displayed the phenotypes of hepatocytes, exhibited classic hepatocyte-associated bio-functions, such as LDL uptake, glycogen storage and urea secretion, as well as possessed the metabolic activities of cytochrome P-450 (CYP) 3A and 2C. Furthermore, we compared the hepatocyte differentiation efficacy of our protocol with another published method, and the results demonstrated that our differentiation strategy could significantly improve the generation of morphological and functional hepatocyte-like cells from porcine iPSCs. In conclusion, this study establishes an efficient method for in vitro generation of functional hepatocytes from porcine iPSCs, which could represent a promising cell source for preclinical testing of cell-based therapeutics for liver failure and for pharmacological applications. PMID:24949734

The early thermal evolution of Mars

NASA Astrophysics Data System (ADS)

Bhatia, G. K.; Sahijpal, S.

2016-01-01

Hf-W isotopic systematics of Martian meteorites have provided evidence for the early accretion and rapid core formation of Mars. We present the results of numerical simulations performed to study the early thermal evolution and planetary scale differentiation of Mars. The simulations are confined to the initial 50 Myr (Ma) of the formation of solar system. The accretion energy produced during the growth of Mars and the decay energy due to the short-lived radio-nuclides 26Al, 60Fe, and the long-lived nuclides, 40K, 235U, 238U, and 232Th are incorporated as the heat sources for the thermal evolution of Mars. During the core-mantle differentiation of Mars, the molten metallic blobs were numerically moved using Stoke's law toward the center with descent velocity that depends on the local acceleration due to gravity. Apart from the accretion and the radioactive heat energies, the gravitational energy produced during the differentiation of Mars and the associated heat transfer is also parametrically incorporated in the present work to make an assessment of its contribution to the early thermal evolution of Mars. We conclude that the accretion energy alone cannot produce widespread melting and differentiation of Mars even with an efficient consumption of the accretion energy. This makes 26Al the prime source for the heating and planetary scale differentiation of Mars. We demonstrate a rapid accretion and core-mantle differentiation of Mars within the initial ~1.5 Myr. This is consistent with the chronological records of Martian meteorites.

A class of exact solutions for biomacromolecule diffusion-reaction in live cells.

PubMed

Sadegh Zadeh, Kouroush; Montas, Hubert J

2010-06-07

A class of novel explicit analytic solutions for a system of n+1 coupled partial differential equations governing biomolecular mass transfer and reaction in living organisms are proposed, evaluated, and analyzed. The solution process uses Laplace and Hankel transforms and results in a recursive convolution of an exponentially scaled Gaussian with modified Bessel functions. The solution is developed for wide range of biomolecular binding kinetics from pure diffusion to multiple binding reactions. The proposed approach provides solutions for both Dirac and Gaussian laser beam (or fluorescence-labeled biomacromolecule) profiles during the course of a Fluorescence Recovery After Photobleaching (FRAP) experiment. We demonstrate that previous models are simplified forms of our theory for special cases. Model analysis indicates that at the early stages of the transport process, biomolecular dynamics is governed by pure diffusion. At large times, the dominant mass transfer process is effective diffusion. Analysis of the sensitivity equations, derived analytically and verified by finite difference differentiation, indicates that experimental biologists should use full space-time profile (instead of the averaged time series) obtained at the early stages of the fluorescence microscopy experiments to extract meaningful physiological information from the protocol. Such a small time frame requires improved bioinstrumentation relative to that in use today. Our mathematical analysis highlights several limitations of the FRAP protocol and provides strategies to improve it. The proposed model can be used to study biomolecular dynamics in molecular biology, targeted drug delivery in normal and cancerous tissues, motor-driven axonal transport in normal and abnormal nervous systems, kinetics of diffusion-controlled reactions between enzyme and substrate, and to validate numerical simulators of biological mass transport processes in vivo. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Self-organization phenomena in embryonic stem cell-derived embryoid bodies: axis formation and breaking of symmetry during cardiomyogenesis.

PubMed

Fuchs, Christiane; Scheinast, Matthias; Pasteiner, Waltraud; Lagger, Sabine; Hofner, Manuela; Hoellrigl, Alexandra; Schultheis, Martina; Weitzer, Georg

2012-01-01

Aggregation of embryonic stem cells gives rise to embryoid bodies (EBs) which undergo developmental processes reminiscent of early eutherian embryonic development. Development of the three germ layers suggests that gastrulation takes place. In vivo, gastrulation is a highly ordered process but in EBs only few data support the hypothesis that self-organization of differentiating cells leads to morphology, reminiscent of the early gastrula. Here we demonstrate that a timely implantation-like process is a prerequisite for the breaking of the radial symmetry of suspended EBs. Attached to a surface, EBs develop a bilateral symmetry and presumptive mesodermal cells emerge between the center of the EBs and a horseshoe-shaped ridge of cells. The development of an epithelial sheet of cells on one side of the EBs allows us to define an 'anterior' and a 'posterior' end of the EBs. In the mesodermal area, first cardiomyocytes (CMCs) develop mainly next to this epithelial sheet of cells. Development of twice as many CMCs at the 'left' side of the EBs breaks the bilateral symmetry and suggests that cardiomyogenesis reflects a local or temporal asymmetry in EBs. The asymmetric appearance of CMCs but not the development of mesoderm can be disturbed by ectopic expression of the muscle-specific protein Desmin. Later, the bilateral morphology becomes blurred by an apparently chaotic differentiation of many cell types. The absence of comparable structures in aggregates of cardiovascular progenitor cells isolated from the heart demonstrates that the self-organization of cells during a gastrulation-like process is a unique feature of embryonic stem cells. Copyright © 2011 S. Karger AG, Basel.

Early nutritional programming affects liver transcriptome in diploid and triploid Atlantic salmon, Salmo salar.

PubMed

Vera, L M; Metochis, C; Taylor, J F; Clarkson, M; Skjærven, K H; Migaud, H; Tocher, D R

2017-11-17

To ensure sustainability of aquaculture, plant-based ingredients are being used in feeds to replace marine-derived products. However, plants contain secondary metabolites which can affect food intake and nutrient utilisation of fish. The application of nutritional stimuli during early development can induce long-term changes in animal physiology. Recently, we successfully used this approach to improve the utilisation of plant-based diets in diploid and triploid Atlantic salmon. In the present study we explored the molecular mechanisms occurring in the liver of salmon when challenged with a plant-based diet in order to determine the metabolic processes affected, and the effect of ploidy. Microarray analysis revealed that nutritional history had a major impact on the expression of genes. Key pathways of intermediary metabolism were up-regulated, including oxidative phosphorylation, pyruvate metabolism, TCA cycle, glycolysis and fatty acid metabolism. Other differentially expressed pathways affected by diet included protein processing in endoplasmic reticulum, RNA transport, endocytosis and purine metabolism. The interaction between diet and ploidy also had an effect on the hepatic transcriptome of salmon. The biological pathways with the highest number of genes affected by this interaction were related to gene transcription and translation, and cell processes such as proliferation, differentiation, communication and membrane trafficking. The present study revealed that nutritional programming induced changes in a large number of metabolic processes in Atlantic salmon, which may be associated with the improved fish performance and nutrient utilisation demonstrated previously. In addition, differences between diploid and triploid salmon were found, supporting recent data that indicate nutritional requirements of triploid salmon may differ from those of their diploid counterparts.

The interpersonal context of client motivational language in cognitive-behavioral therapy.

PubMed

Sijercic, Iris; Button, Melissa L; Westra, Henny A; Hara, Kimberley M

2016-03-01

Previous research has found that client motivational language (especially arguments against change or counterchange talk; CCT) in early therapy sessions is a reliable predictor of therapy process and outcomes across a broad range of treatments including cognitive-behavioral therapy (CBT). Existing studies have considered the general occurrence of CCT, but the present study differentiated 2 types of CCT in early CBT sessions for 37 clients with generalized anxiety disorder: (a) statements that are uttered to express ambivalence regarding change versus (b) statements that are intended to oppose the therapist or therapy. Two process coding systems were used to accomplish this differentiation. Findings indicated that a higher number of CCT statements that occurred in the presence of resistance (opposition to the therapist or therapy) were a substantive and consistent predictor of lower homework compliance and poorer outcomes, up to 1 year posttreatment. Moreover, when both types of CCT were considered together, only opposition CCT was related to outcomes, and ambivalent CCT was not significantly predictive of proximal and distal outcomes. These findings suggest that the interpersonal context in which CCT statements occur may be critically important to their predictive capacity. More broadly, the findings of this study have implications for the future study of client motivational language and underscore the clinical importance of detecting opposition CCT. (c) 2016 APA, all rights reserved).

Proteomic Profile of Mabuya sp. (Squamata: Scincidae) Ovary and Placenta During Gestation.

PubMed

Hernández-Díaz, Nathaly; Torres, Rodrigo; Ramírez-Pinilla, Martha Patricia

2017-06-01

Reptiles are one of the most diverse groups of vertebrates, providing an integrated system for comparative studies on metabolic, animal physiology, and developmental biology. However, the molecular data available are limited and only recently have started to call attention in the "omics" sciences. Mabuya sp. is a viviparous placentrotrophic skink with particular reproductive features, including microlecithal eggs, early luteolysis, prolonged gestation, and development of a highly specialized placenta. This placenta is responsible for respiratory exchange and the transference of all nutrients necessary for embryonic development. Our aim was to identify differentially expressed proteins in the ovary and placenta of Mabuya sp. during early, mid, and late gestation; their possible metabolic pathways; and biological processes. We carried out a comparative proteomic analysis during gestation in both tissues by sodium dodecyl sulfate polyacrylamide gel electrophoresis, two-dimensional gel electrophoresis, and matrix-assisted laser desorption/ionization. Differential protein expression in both tissues (Student's t-test P < 0.05) was related to several processes such as cell structure, cell movement, and energy. Proteins found in ovary are mainly associated with follicular development and its regulation. In the placenta, particularly during mid and late gestation, protein expression is involved in nutrient metabolism, transport, protein synthesis, and embryonic development. This work provides new insights about the proteins expressed and their physiological mechanisms in Mabuya sp. placenta and ovary during gestation. © 2017 Wiley Periodicals, Inc.

Musical rhythm and pitch: A differential effect on auditory dynamics as revealed by the N1/MMN/P3a complex.

PubMed

Lelo-de-Larrea-Mancera, E Sebastian; Rodríguez-Agudelo, Yaneth; Solís-Vivanco, Rodolfo

2017-06-01

Music represents a complex form of human cognition. To what extent our auditory system is attuned to music is yet to be clearly understood. Our principal aim was to determine whether the neurophysiological operations underlying pre-attentive auditory change detection (N1 enhancement (N1e)/Mismatch Negativity (MMN)) and the subsequent involuntary attentional reallocation (P3a) towards infrequent sound omissions, are influenced by differences in musical content. Specifically, we intended to explore any interaction effects that rhythmic and pitch dimensions of musical organization may have over these processes. Results showed that both the N1e and MMN amplitudes were differentially influenced by rhythm and pitch dimensions. MMN latencies were shorter for musical structures containing both features. This suggests some neurocognitive independence between pitch and rhythm domains, but also calls for further address on possible interactions between both of them at the level of early, automatic auditory detection. Furthermore, results demonstrate that the N1e reflects basic sensory memory processes. Lastly, we show that the involuntary switch of attention associated with the P3a reflects a general-purpose mechanism not modulated by musical features. Altogether, the N1e/MMN/P3a complex elicited by infrequent sound omissions revealed evidence of musical influence over early stages of auditory perception. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ectopic expression of the Coffea canephora SERK1 homolog-induced differential transcription of genes involved in auxin metabolism and in the developmental control of embryogenesis.

PubMed

Pérez-Pascual, Daniel; Jiménez-Guillen, Doribet; Villanueva-Alonzo, Hernán; Souza-Perera, Ramón; Godoy-Hernández, Gregorio; Zúñiga-Aguilar, José Juan

2018-04-01

Somatic embryogenesis receptor-like kinase 1 (SERK1) is a membrane receptor that might serve as common co-regulator of plant cell differentiation processes by forming heterodimers with specific receptor-like kinases. The Coffea canephora SERK1 homolog (CcSERK1) was cloned in this work, and its early function in the transcription of embryogenesis master genes and of genes encoding proteins involved in auxin metabolism was investigated by externally manipulating its expression in embryogenic leaf explants, before the appearance of embryogenic structures. Overexpression of CcSERK1 early during embryogenesis caused an increase in the number of somatic embryos when the 55-day process was completed. Suppression of CcSERK1 expression by RNA interference almost abolished somatic embryogenesis. Real time-PCR experiments revealed that the transcription of the CcAGL15, CcWUS, CcBBM, CcPKL, CcYUC1, CcPIN1 and CcPIN4 homologs was modified in direct proportion to the expression of CcSERK1 and that only CcLEC1 was inversely affected by the expression levels of CcSERK1. The expression of the CcYUC4 homolog was induced to more than 80-fold under CcSERK1 overexpression conditions, but it was also induced when CcSERK1 expression was silenced. The level of CcTIR1 was not affected by CcSERK1 overexpression but was almost abolished during CcSERK1 silencing. These results suggest that CcSERK1 co-regulates the induction of somatic embryogenesis in Coffea canephora by early activation of YUC-dependent auxin biosynthesis, auxin transport mediated by PIN1 and PIN4, and probably auxin perception by the TIR1 receptor, leading to the induction of early-stage homeotic genes (CcAGL15, CcWUS, CcPKL and CcBBM) and repression of late-stage homeotic genes (CcLec1). © 2018 Scandinavian Plant Physiology Society.

Parvovirus B19 Replication and Expression in Differentiating Erythroid Progenitor Cells

PubMed Central

Bua, Gloria; Manaresi, Elisabetta; Bonvicini, Francesca; Gallinella, Giorgio

2016-01-01

The pathogenic Parvovirus B19 (B19V) is characterized by a strict adaptation to erythroid progenitor cells (EPCs), a heterogeneous population of differentiating cells with diverse phenotypic and functional properties. In our work, we studied the dynamics of B19V infection in EPCs in dependence on the cell differentiation stage, in terms of distribution of infected cells, synthesis of viral nucleic acids and production of infectious virus. EPCs at early differentiation stage led to an abortive infection, without viral genome replication and a very low transcriptional activity. EPCs at later stages were permissive, with highest levels of viral replicative activity at day 9 (+3.0 Log from 2 to 48 hpi) and lower levels at day 18 (+1.5 Log from 2 to 48 hpi). B19V DNA increment was in accordance with the percentage of cells positive to flow-FISH assay (41.4% at day 9, 1.1% at day 18). Quantitation of total RNA indicated a close association of genome replication and transcription with viral RNA accumulation within infected cells related to viral DNA increase during the course of infection. Analysis of the different classes of mRNAs revealed two distinct pattern of genome expression profile with a fine regulation in the frequency utilization of RNA processing signals: an early phase, when cleavage at the proximal site leading to a higher relative production of mRNA for NS protein, and a late phase, when cleavage at the distal site was more frequent leading to higher relative abundance of mRNA for VP and 11 kDA proteins. Infectious virus was released from cells at day 6–15, but not at day 18. Our results, providing a detailed description of B19V replication and expression profile in differentiating EPCs, highlight the very tight adaptation of B19V to a specific cellular target defined both by its erythroid lineage and its differentiation stage. PMID:26845771

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

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.

Differential contribution of early visual areas to the perceptual process of contour processing.

PubMed

Schira, Mark M; Fahle, Manfred; Donner, Tobias H; Kraft, Antje; Brandt, Stephan A

2004-04-01

We investigated contour processing and figure-ground detection within human retinotopic areas using event-related functional magnetic resonance imaging (fMRI) in 6 healthy and naïve subjects. A figure (6 degrees side length) was created by a 2nd-order texture contour. An independent and demanding foveal letter-discrimination task prevented subjects from noticing this more peripheral contour stimulus. The contour subdivided our stimulus into a figure and a ground. Using localizers and retinotopic mapping stimuli we were able to subdivide each early visual area into 3 eccentricity regions corresponding to 1) the central figure, 2) the area along the contour, and 3) the background. In these subregions we investigated the hemodynamic responses to our stimuli and compared responses with or without the contour defining the figure. No contour-related blood oxygenation level-dependent modulation in early visual areas V1, V3, VP, and MT+ was found. Significant signal modulation in the contour subregions of V2v, V2d, V3a, and LO occurred. This activation pattern was different from comparable studies, which might be attributable to the letter-discrimination task reducing confounding attentional modulation. In V3a, but not in any other retinotopic area, signal modulation corresponding to the central figure could be detected. Such contextual modulation will be discussed in light of the recurrent processing hypothesis and the role of visual awareness.

White matter maturation profiles through early childhood predict general cognitive ability.

PubMed

Deoni, Sean C L; O'Muircheartaigh, Jonathan; Elison, Jed T; Walker, Lindsay; Doernberg, Ellen; Waskiewicz, Nicole; Dirks, Holly; Piryatinsky, Irene; Dean, Doug C; Jumbe, N L

2016-03-01

Infancy and early childhood are periods of rapid brain development, during which brain structure and function mature alongside evolving cognitive ability. An important neurodevelopmental process during this postnatal period is the maturation of the myelinated white matter, which facilitates rapid communication across neural systems and networks. Though prior brain imaging studies in children (4 years of age and above), adolescents, and adults have consistently linked white matter development with cognitive maturation and intelligence, few studies have examined how these processes are related throughout early development (birth to 4 years of age). Here, we show that the profile of white matter myelination across the first 5 years of life is strongly and specifically related to cognitive ability. Using a longitudinal design, coupled with advanced magnetic resonance imaging, we demonstrate that children with above-average ability show differential trajectories of myelin development compared to average and below average ability children, even when controlling for socioeconomic status, gestation, and birth weight. Specifically, higher ability children exhibit slower but more prolonged early development, resulting in overall increased myelin measures by ~3 years of age. These results provide new insight into the early neuroanatomical correlates of cognitive ability, and suggest an early period of prolonged maturation with associated protracted white matter plasticity may result in strengthened neural networks that can better support later development. Further, these results reinforce the necessity of a longitudinal perspective in investigating typical or suspected atypical cognitive maturation.

Comparative 2D-DIGE proteomic analysis of bovine mammary epithelial cells during lactation reveals protein signatures for lactation persistency and milk yield.

PubMed

Janjanam, Jagadeesh; Singh, Surender; Jena, Manoj K; Varshney, Nishant; Kola, Srujana; Kumar, Sudarshan; Kaushik, Jai K; Grover, Sunita; Dang, Ajay K; Mukesh, Manishi; Prakash, B S; Mohanty, Ashok K

2014-01-01

Mammary gland is made up of a branching network of ducts that end with alveoli which surrounds the lumen. These alveolar mammary epithelial cells (MEC) reflect the milk producing ability of farm animals. In this study, we have used 2D-DIGE and mass spectrometry to identify the protein changes in MEC during immediate early, peak and late stages of lactation and also compared differentially expressed proteins in MEC isolated from milk of high and low milk producing cows. We have identified 41 differentially expressed proteins during lactation stages and 22 proteins in high and low milk yielding cows. Bioinformatics analysis showed that a majority of the differentially expressed proteins are associated in metabolic process, catalytic and binding activity. The differentially expressed proteins were mapped to the available biological pathways and networks involved in lactation. The proteins up-regulated during late stage of lactation are associated with NF-κB stress induced signaling pathways and whereas Akt, PI3K and p38/MAPK signaling pathways are associated with high milk production mediated through insulin hormone signaling.

A behavioral task with more opportunities for memory acquisition promotes the survival of new neurons in the adult dentate gyrus.

PubMed

Aasebø, Ida E J; Kasture, Ameya Sanjay; Passeggeri, Marzia; Tashiro, Ayumu

2018-05-09

It has been suggested that the dentate gyrus, particularly its new neurons generated via adult neurogenesis, is involved in memory acquisition and recall. Here, we trained rats in two types of Morris water maze tasks that are differentially associated with these two memory processes, and examined whether new neurons are differently affected by the two tasks performed during the second week of neuronal birth. Our results indicate that the task involving more opportunities to acquire new information better supports the survival of new neurons. Further, we assessed whether the two tasks differentially induce the expression of an immediate early gene, Zif268, which is known to be induced by neuronal activation. While the two tasks differentially induce Zif268 expression in the dentate gyrus, the proportions of new neurons activated were similar between the two tasks. Thus, we conclude that while the two tasks differentially activate the dentate gyrus, the task involving more opportunities for memory acquisition during the second week of the birth of new neurons better promotes the survival of the new neurons.

Tower of London test: a comparison between conventional statistic approach and modelling based on artificial neural network in differentiating fronto-temporal dementia from Alzheimer's disease.

PubMed

Franceschi, Massimo; Caffarra, Paolo; Savarè, Rita; Cerutti, Renata; Grossi, Enzo

2011-01-01

The early differentiation of Alzheimer's disease (AD) from frontotemporal dementia (FTD) may be difficult. The Tower of London (ToL), thought to assess executive functions such as planning and visuo-spatial working memory, could help in this purpose. Twentytwo Dementia Centers consecutively recruited patients with early FTD or AD. ToL performances of these groups were analyzed using both the conventional statistical approaches and the Artificial Neural Networks (ANNs) modelling. Ninety-four non aphasic FTD and 160 AD patients were recruited. ToL Accuracy Score (AS) significantly (p < 0.05) differentiated FTD from AD patients. However, the discriminant validity of AS checked by ROC curve analysis, yielded no significant results in terms of sensitivity and specificity (AUC 0.63). The performances of the 12 Success Subscores (SS) together with age, gender and schooling years were entered into advanced ANNs developed by Semeion Institute. The best ANNs were selected and submitted to ROC curves. The non-linear model was able to discriminate FTD from AD with an average AUC for 7 independent trials of 0.82. The use of hidden information contained in the different items of ToL and the non linear processing of the data through ANNs allows a high discrimination between FTD and AD in individual patients.

New potential markers of in vitro tomato morphogenesis identified by mRNA differential display.

PubMed

Torelli, A; Soragni, E; Bolchi, A; Petrucco, S; Ottonello, S; Branca, C

1996-12-01

The identification of plant genes involved in early phases of in vitro morphogenesis can not only contribute to our understanding of the processes underlying growth regulator-controlled determination, but also provide novel markers for evaluating the outcome of in vitro regeneration experiments. To search for such genes and to monitor changes in gene expression accompanying in vitro regeneration, we have adapted the mRNA differential display technique to the comparative analysis of a model system of tomato cotyledons that can be driven selectively toward either shoot or callus formation by means of previously determined growth regulator supplementations. Hormone-independent transcriptional modulation (mainly down-regulation) has been found to be the most common event, indicating that a non-specific reprogramming of gene expression quantitatively predominates during the early phases of in vitro culture. However, cDNA fragments representative of genes that are either down-regulated or induced in a programme-specific manner could also be identified, and two of them (G35, G36) were further characterized. One of these cDNA fragments, G35, corresponds to an mRNA that is down-regulated much earlier in callus- (day 2) than in shoot-determined explants (day 6). The other, G36, identifies an mRNA that is transiently expressed in shoot-determined explants only, well before any macroscopic signs of differentiation become apparent, and thus exhibits typical features of a morphogenetic marker.

Identification of prohibitin 1 as a potential prognostic biomarker in human pancreatic carcinoma using modified aqueous two-phase partition system combined with 2D-MALDI-TOF-TOF-MS/MS.

PubMed

Zhong, Ning; Cui, Yazhou; Zhou, Xiaoyan; Li, Tianliang; Han, Jinxiang

2015-02-01

Membrane proteins are an important source of potential targets for anticancer drugs or biomarkers for early diagnosis. In this study, we used a modified aqueous two-phase partition system combined with two-dimensional (2D) matrix-assisted laser desorption ionization (MALDI) time of flight (TOF) mass spectrometry (MS, 2D-MALDI-TOF-TOF-MS/MS) analysis to isolate and identify membrane proteins in PANC-1 pancreatic cancer cells. Using this method, we identified 55 proteins, of which 31 (56.4 %) were membrane proteins, which, according to gene ontology annotation, are associated with various cellular processes including cell signal transduction, differentiation, and apoptosis. Immunohistochemical analysis showed that the expression level of one of the identified mitochondria membrane proteins, prohibitin 1 (PHB1), is correlated with pancreatic carcinoma differentiation; PHB1 is expressed at a higher level in normal pancreatic tissue than in well-differentiated carcinoma tissue. Further studies showed that PHB1 plays a proapoptotic role in human pancreatic cancer cells, which suggests that PHB1 has antitumorigenic properties. In conclusion, we have provided a modified method for isolating and identifying membrane proteins and demonstrated that PHB1 may be a promising biomarker for early diagnosis and therapy of pancreatic (and potentially other) cancers.

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.

Proteomic analysis of 'Zaosu' pear (Pyrus bretschneideri Rehd.) and its early-maturing bud sport.

PubMed

Liu, Xueting; Zhai, Rui; Feng, Wenting; Zhang, Shiwei; Wang, Zhigang; Qiu, Zonghao; Zhang, Junke; Ma, Fengwang; Xu, Lingfei

2014-07-01

Maturation of fruits involves a series of physiological, biochemical, and organoleptic changes that eventually make fleshy fruits attractive, palatable, and nutritional. In order to understand the mature mechanism of the early-maturing bud sport of 'Zaosu' pear, we analyzed the differences of proteome expression between the both pears in different mature stages by the methods of a combination of two-dimensional electrophoresis (2-DE) and matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis. Seventy-five differential expressed protein spots (p<0.05) were obtained between 'Zaosu' pear and its early-maturing bud sport, but only sixty-eight were demonstratively identified in the database of NCBI and uniprot. The majority of proteins were linked to metabolism, energy, stress response/defense and cell structure. Additionally, our data confirmed an increase of proteins related to cell-wall modification, oxidative stress and pentose phosphate metabolism and a decrease of proteins related to photosynthesis and glycolysis during the development process of both pears, but all these proteins increased or decreased faster in the early-maturing bud sport. This comparative analysis between both pears showed that these proteins were closely associated with maturation and could provide more detailed characteristics of the maturation process of both pears. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The lasting effects of process-specific versus stimulus-specific learning during infancy.

PubMed

Hadley, Hillary; Pickron, Charisse B; Scott, Lisa S

2015-09-01

The capacity to tell the difference between two faces within an infrequently experienced face group (e.g. other species, other race) declines from 6 to 9 months of age unless infants learn to match these faces with individual-level names. Similarly, the use of individual-level labels can also facilitate differentiation of a group of non-face objects (strollers). This early learning leads to increased neural specialization for previously unfamiliar face or object groups. The current investigation aimed to determine whether early conceptual learning between 6 and 9 months leads to sustained behavioral advantages and neural changes in these same children at 4-6 years of age. Results suggest that relative to a control group of children with no previous training and to children with infant category-level naming experience, children with early individual-level training exhibited faster response times to human faces. Further, individual-level training with a face group - but not an object group - led to more adult-like neural responses for human faces. These results suggest that early individual-level learning results in long-lasting process-specific effects, which benefit categories that continue to be perceived and recognized at the individual level (e.g. human faces). © 2014 John Wiley & Sons Ltd.

Neural correlates of processing negative and sexually arousing pictures.

PubMed

Bailey, Kira; West, Robert; Mullaney, Kellie M

2012-01-01

Recent work has questioned whether the negativity bias is a distinct component of affective picture processing. The current study was designed to determine whether there are different neural correlates of processing positive and negative pictures using event-related brain potentials. The early posterior negativity and late positive potential were greatest in amplitude for erotic pictures. Partial Least Squares analysis revealed one latent variable that distinguished erotic pictures from neutral and positive pictures and another that differentiated negative pictures from neutral and positive pictures. The effects of orienting task on the neural correlates of processing negative and erotic pictures indicate that affective picture processing is sensitive to both stimulus-driven, and attentional or decision processes. The current data, together with other recent findings from our laboratory, lead to the suggestion that there are distinct neural correlates of processing negative and positive stimuli during affective picture processing.

Neural Correlates of Processing Negative and Sexually Arousing Pictures

PubMed Central

Bailey, Kira; West, Robert; Mullaney, Kellie M.

2012-01-01

Recent work has questioned whether the negativity bias is a distinct component of affective picture processing. The current study was designed to determine whether there are different neural correlates of processing positive and negative pictures using event-related brain potentials. The early posterior negativity and late positive potential were greatest in amplitude for erotic pictures. Partial Least Squares analysis revealed one latent variable that distinguished erotic pictures from neutral and positive pictures and another that differentiated negative pictures from neutral and positive pictures. The effects of orienting task on the neural correlates of processing negative and erotic pictures indicate that affective picture processing is sensitive to both stimulus-driven, and attentional or decision processes. The current data, together with other recent findings from our laboratory, lead to the suggestion that there are distinct neural correlates of processing negative and positive stimuli during affective picture processing. PMID:23029071

Identification and Characterization of Three Differentially Expressed Genes, Encoding S-Adenosylhomocysteine Hydrolase, Methionine Aminopeptidase, and a Histone-Like Protein, in the Toxic Dinoflagellate Alexandrium fundyense†

PubMed Central

Taroncher-Oldenburg, Gaspar; Anderson, Donald M.

2000-01-01

Genes showing differential expression related to the early G1 phase of the cell cycle during synchronized circadian growth of the toxic dinoflagellate Alexandrium fundyense were identified and characterized by differential display (DD). The determination in our previous work that toxin production in Alexandrium is relegated to a narrow time frame in early G1 led to the hypothesis that transcriptionally up- or downregulated genes during this subphase of the cell cycle might be related to toxin biosynthesis. Three genes, encoding S-adenosylhomocysteine hydrolase (Sahh), methionine aminopeptidase (Map), and a histone-like protein (HAf), were isolated. Sahh was downregulated, while Map and HAf were upregulated, during the early G1 phase of the cell cycle. Sahh and Map encoded amino acid sequences with about 90 and 70% similarity to those encoded by several eukaryotic and prokaryotic Sahh and Map genes, respectively. The partial Map sequence also contained three cobalt binding motifs characteristic of all Map genes. HAf encoded an amino acid sequence with 60% similarity to those of two histone-like proteins from the dinoflagellate Crypthecodinium cohnii Biecheler. This study documents the potential of applying DD to the identification of genes that are related to physiological processes or cell cycle events in phytoplankton under conditions where small sample volumes represent an experimental constraint. The identification of an additional 21 genes with various cell cycle-related DD patterns also provides evidence for the importance of pretranslational or transcriptional regulation in dinoflagellates, contrary to previous reports suggesting the possibility that translational mechanisms are the primary means of circadian regulation in this group of organisms. PMID:10788388

By Permission of the Mantle: Modern and Ancient Deep Earth Volatile Cycles

NASA Astrophysics Data System (ADS)

Hirschmann, M. M.

2011-12-01

The principle volatile elements, H and C, are of surpassing importance to processes and conditions in the interiors and the surfaces of terrestrial planets, affecting everything from mantle dynamics and large scale geochemical differentiation to climate and habitability. The storage of these volatiles in planetary interiors, their inventory in the near-surface environment and exchange between the interiors and the exosphere are governed by petrologic processes. Were it not for the effective incompatibility of these components in mantle lithologies, there might be no oceans, no habitable climate, and no biosphere on the surface. Consequently, deep Earth volatile cycles represent one of the best examples of how petrology influences nearly all other aspects of Earth science. The exosphere of the modern Earth has a high H/C ratio compared to that of the interior sampled by oceanic basalts. A potential explanation for this is that C is subducted to the deep mantle more efficiently than H, such that the exosphere C reservoir shrinks through geologic time. Unfortunately this hypothesis conflicts with the sedimentary record, which suggests that carbonate storage on the continents has increased rather than decreased with time. It also may not be applicable to the first 3 Ga of Earth history, when hotter typical subduction geotherms greatly reduced the efficiency of C subduction. An important question regarding deep Earth volatile cycles is the inventory of H and C in the interior and the exosphere that descend from Earth's earliest differentiation processes. Originally, much of Earth's volatile inventory was presumably present as a thick atmosphere, in part because volatiles were probably delivered late in the accretion history and owing to both the efficiency of impact degassing and of volatile release from early magma ocean(s). Early mantle H2O may descend from the magma ocean, in which portions of a steam atmosphere are dissolved in the magma and then precipitated with nominally anhydrous minerals. In contrast, low magmatic solubility of C-bearing species would suggest that the early mantle was depleted in carbon. Thus, the earliest Earth could have been characterized by an exosphere with low H/C and a mantle with high H/C - the reverse of the modern case. An alternative hypothesis is that significant C was sequestered in the early mantle as a reduced phase- diamond, carbide, or alloy - precipitated during magma ocean solidification. Despite low solubility in magmas, early atmospheric carbon may have been incorporated into solidifying mantle if C solubility diminished with increasing magma ocean depth. Volatile solubilities in magmas typically increase with increasing pressure, but the opposite could be true for C if conditions were more reducing at depth and more oxidizing near the surface. Such conditions would allow operation of a carbon pump, transporting early atmospheric carbon to the solidifying mantle. If such a process operated, then the modern mantle/exosphere H/C fractionation is likely a remnant of this early process. If not, some other explanation for Earth's distribution of H and C must be sought.

Modality-specificity of sensory aging in vision and audition: evidence from event-related potentials.

PubMed

Ceponiene, R; Westerfield, M; Torki, M; Townsend, J

2008-06-18

Major accounts of aging implicate changes in processing external stimulus information. Little is known about differential effects of auditory and visual sensory aging, and the mechanisms of sensory aging are still poorly understood. Using event-related potentials (ERPs) elicited by unattended stimuli in younger (M=25.5 yrs) and older (M=71.3 yrs) subjects, this study examined mechanisms of sensory aging under minimized attention conditions. Auditory and visual modalities were examined to address modality-specificity vs. generality of sensory aging. Between-modality differences were robust. The earlier-latency responses (P1, N1) were unaffected in the auditory modality but were diminished in the visual modality. The auditory N2 and early visual N2 were diminished. Two similarities between the modalities were age-related enhancements in the late P2 range and positive behavior-early N2 correlation, the latter suggesting that N2 may reflect long-latency inhibition of irrelevant stimuli. Since there is no evidence for salient differences in neuro-biological aging between the two sensory regions, the observed between-modality differences are best explained by the differential reliance of auditory and visual systems on attention. Visual sensory processing relies on facilitation by visuo-spatial attention, withdrawal of which appears to be more disadvantageous in older populations. In contrast, auditory processing is equipped with powerful inhibitory capacities. However, when the whole auditory modality is unattended, thalamo-cortical gating deficits may not manifest in the elderly. In contrast, ERP indices of longer-latency, stimulus-level inhibitory modulation appear to diminish with age.

Importance of ERK activation in As2O3-induced differentiation and promyelocytic leukemia nuclear bodies formation in neuroblastoma cells.

PubMed

Petit, A; Delaune, A; Falluel-Morel, A; Goullé, J-P; Vannier, J-P; Dubus, I; Vasse, M

2013-11-01

Neuroblastoma malignant cell growth is dependent on their undifferentiated status. Arsenic trioxide (As2O3) induces neuroblastoma cell differentiation in vitro, but its mechanisms still remains unknown. We used three human neuroblastoma cell lines (SH-SY5Y, IGR-N-91, LAN-1) that differ from their MYCN and p53 status to explore the intracellular events activated by As2O3 and involved in neurite outgrowth, a morphological marker of differentiation. As2O3 (2μM) induced neurite outgrowth in all cell lines, which was dependent on ERK activation but independent on MYCN status. This process was induced either by a sustained (3 days) or a transient (2h) incubation with As2O3, indicating that very early events trigger the induction of differentiation. In parallel, As2O3 induced a rapid assembly of promyelocytic leukemia nuclear bodies (PML-NB) in an ERK-dependent manner. In conclusion, mechanisms leading to neuroblastoma cell differentiation in response to As2O3 appear to involve the ERK pathway activation and PML-NB formation, which are observed in response to other differentiating molecules such as retinoic acid derivates. This open new perspectives based on the use of treatment combinations to potentiate the differentiating effects of each drug alone and reduce their adverse side effects. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

The altered expression of perineuronal net elements during neural differentiation.

PubMed

Eskici, Nazli F; Erdem-Ozdamar, Sevim; Dayangac-Erden, Didem

2018-01-01

Perineuronal nets (PNNs), which are localized around neurons during development, are specialized forms of neural extracellular matrix with neuroprotective and plasticity-regulating roles. Hyaluronan and proteoglycan link protein 1 (HAPLN1), tenascin-R (TNR) and aggrecan (ACAN) are key elements of PNNs. In diseases characterized by neuritogenesis defects, the expression of these proteins is known to be downregulated, suggesting that PNNs may have a role in neural differentiation. In this study, the mRNA and protein levels of HAPLN1, TNR and ACAN were determined and compared at specific time points of neural differentiation. We used PC12 cells as the in vitro model because they reflect this developmental process. On day 7, the HAPLN1 mRNA level showed a 2.9-fold increase compared to the non-differentiated state. However, the cellular HAPLN1 protein level showed a decrease, indicating that the protein may have roles in neural differentiation, and may be secreted during the early period of differentiation. By contrast, TNR mRNA and protein levels remained unchanged, and the amount of cellular ACAN protein showed a 3.7-fold increase at day 7. These results suggest that ACAN may be secreted after day 7, possibly due to its large amount of post-translational modifications. Our results provide preliminary data on the expression of PNN elements during neural differentiation. Further investigations will be performed on the role of these elements in neurological disease models.

[Paraneoplastic vasculitis in a patient with cervical cancer].

PubMed

Kohútek, F; Rosík, A; Izák, N; Tamášová, M; Bystrický, B

2014-01-01

Paraneoplastic syndromes precede the dia-gnosis of malignancy. Early detection of paraneoplastic syndrome may lead to detection of malignancy in its early and potentially curable stage. Differential diagnostic process of rare paraneoplastic vasculitis requires multidisciplinary cooperation between rheumatologists, radiologists and oncologists. 41 year old female patient with cervical cancer in stage IVB (paraaortic lymphadenopathy) and clinical symptoms of acute vasculitis was admitted to our ward for oncological treatment. Chemoradiotheraphy was initiated concurrently with corticotherapy. During the treatment we observed alleviation of vasculitis related symptoms. Ongoing followup, however, brought no further improvement in vasculitis related symptoms. This lead us to suspicion of recurrence, confirmed on CT scan. Palliative chemotherapy was without any effect and due to worsening performance status was terminated. The activity of vasculitis was closely associated with the activity of primary malignant disease. Early recognition of paraneoplastic syndrome may contribute not only to dia-gnosis of malignancy, but is helpful during followup of these patients.

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.

PKR is a novel functional direct player that coordinates skeletal muscle differentiation via p38MAPK/AKT pathways.

PubMed

Alisi, A; Spaziani, A; Anticoli, S; Ghidinelli, M; Balsano, C

2008-03-01

Myogenic differentiation is a highly orchestrated multistep process controlled by extracellular growth factors that modulate largely unknown signals into the cell affecting the muscle-transcription program. P38MAPK-dependent signalling, as well as PI3K/Akt pathway, has a key role in the control of muscle gene expression at different stages during the myogenic process. P38MAPK affects the activities of transcription factors, such as MyoD and myogenin, and contributes, together with PI3K/Akt pathway, to control the early and late steps of myogenic differentiation. The aim of our work was to better define the role of PKR, a dsRNA-activated protein kinase, as potential component in the differentiation program of C2C12 murine myogenic cells and to correlate its activity with p38MAPK and PI3K/Akt myogenic regulatory pathways. Here, we demonstrate that PKR is an essential component of the muscle development machinery and forms a functional complex with p38MAPK and/or Akt, contributing to muscle differentiation of committed myogenic cells in vitro. Inhibition of endogenous PKR activity by a specific (si)RNA and a PKR dominant-negative interferes with the myogenic program of C2C12 cells, causing a delay in activation of myogenic specific genes and inducing the formation of thinner myofibers. In addition, the construction of three PKR mutants allowed us to demonstrate that both N and C-terminal regions of PKR are critical for the interaction with p38MAPK and Akt. The novel discovered complex permits PKR to timely regulate the inhibition/activation of p38MAPK and Akt, controlling in this way the different steps characterizing skeletal muscle differentiation.

Transcriptomic profile of leg muscle during early growth in chicken

PubMed Central

Zhang, Genxi; Li, Tingting; Ling, Jiaojiao; Zhang, Xiangqian; Wang, Jinyu

2017-01-01

The early growth pattern, especially the age of peak growth, of broilers affects the time to market and slaughter weight, which in turn affect the profitability of the poultry industry. However, the underlying mechanisms regulating chicken growth and development have rarely been studied. This study aimed to identify candidate genes involved in chicken growth and investigated the potential regulatory mechanisms of early growth in chicken. RNA sequencing was applied to compare the transcriptomes of chicken muscle tissues at three developmental stages during early growth. In total, 978 differentially expressed genes (DEGs) (fold change ≥ 2; false discovery rate < 0.05) were detected by pairwise comparison. Functional analysis showed that the DEGs are mainly involved in the processes of cell growth, muscle development, and cellular activities (such as junction, migration, assembly, differentiation, and proliferation). Many of the DEGs are well known to be related to chicken growth, such as MYOD1, GH, IGF2BP2, IGFBP3, SMYD1, CEBPB, FGF2, and IGFBP5. KEGG pathway analysis identified that the DEGs were significantly enriched in five pathways (P < 0.1) related to growth and development: extracellular matrix–receptor interaction, focal adhesion, tight junction, insulin signaling pathway, and regulation of the actin cytoskeleton. A total of 42 DEGs assigned to these pathways are potential candidate genes inducing the difference in growth among the three developmental stages, such as MYH10, FGF2, FGF16, FN1, CFL2, MAPK9, IRS1, PHKA1, PHKB, and PHKG1. Thus, our study identified a series of genes and several pathways that may participate in the regulation of early growth in chicken. These results should serve as an important resource revealing the molecular basis of chicken growth and development. PMID:28291821

Molecular magnetic resonance imaging of atherosclerotic vessel wall disease.

PubMed

Nörenberg, Dominik; Ebersberger, Hans U; Diederichs, Gerd; Hamm, Bernd; Botnar, René M; Makowski, Marcus R

2016-03-01

Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. Targeted MR-probes allow the characterization of atherosclerosis on a molecular level. Molecular MRI can identify in vivo markers for the differentiation of stable and unstable plaques. Visualization of early molecular changes has the potential to improve patient-individualized risk-assessment.

C145 as a short-latency electrophysiological index of cognitive compensation in Alzheimer's disease

PubMed Central

Chapman, Robert M.; Porsteinsson, Anton P.; Gardner, Margaret N.; Mapstone, Mark; McCrary, John W.; Sandoval, Tiffany C.; Guillily, Maria D.; DeGrush, Elizabeth; Reilly, Lindsey A.

2012-01-01

Brain plasticity and cognitive compensation in the elderly are of increasing interest, and Alzheimer's disease (AD) offers an opportunity to elucidate how the brain may overcome damage. We provide neurophysiological evidence of a short-latency ERP component (C145) linked to stimulus relevancy that may reflect cognitive compensation in early-stage Alzheimer's disease (AD). Thirty-six subjects with early-stage, mild AD and 36 like-aged normal elderly (Controls) had their EEG recorded while performing our Number-Letter task, a cognitive/perceptual paradigm that manipulates stimulus relevancies. ERP components, including C145, were extracted from ERPs using Principal Components Analysis. C145 amplitudes and spatial distributions were compared among Controls, AD subjects with high performance on the Number-Letter task, and AD subjects with low performance. Compared to AD subjects, Control subjects showed enhanced C145 processing of visual stimuli in the occipital region where differential processing of relevant stimuli occurred. AD high performers recruited central brain areas in processing task relevancy. Controls and AD low performers did not show a significant task relevancy effect in these areas. We conclude that short-latency ERP components can detect electrophysiological differences in early-stage AD that reflect altered cognition. Differences in C145 amplitudes between AD and normal elderly groups regarding brain locations and types of task effects suggest compensatory mechanisms can occur in the AD brain to overcome loss of normal functionality, and this early compensation may have a profound effect on the cognitive efficiency of AD individuals. PMID:22886016

Early differentiation of the Moon: Experimental and modeling studies

NASA Technical Reports Server (NTRS)

Longhi, J.

1986-01-01

Major accomplishments include the mapping out of liquidus boundaries of lunar and meteoritic basalts at low pressure; the refinement of computer models that simulate low pressure fractional crystallization; the development of a computer model to calculate high pressure partial melting of the lunar and Martian interiors; and the proposal of a hypothesis of early lunar differentiation based upon terrestrial analogs.

Differential Susceptibility in Early Literacy Instruction through Computer Games: The Role of the Dopamine D4 Receptor Gene (DRD4)

ERIC Educational Resources Information Center

Kegel, Cornelia A. T.; Bus, Adriana G.; van IJzendoorn, Marinus H.

2011-01-01

Not every child seems equally susceptible to the same parental, educational, or environmental influences even if cognitive level is similar. This study is the first randomized controlled trial to apply the differential susceptibility paradigm to education in relation to children's genotype and early literacy skills. A randomized pretest-posttest…

Six1 overexpression at early stages of HPV16-mediated transformation of human keratinocytes promotes differentiation resistance and EMT

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

Xu, Hanwen; Pirisi, Lucia; Creek, Kim E., E-mail: creekk@sccp.sc.edu

Previous studies in our laboratory discovered that SIX1 mRNA expression increased during in vitro progression of HPV16-immortalized human keratinocytes (HKc/HPV16) toward a differentiation-resistant (HKc/DR) phenotype. In this study, we explored the role of Six1 at early stages of HPV16-mediated transformation by overexpressing Six1 in HKc/HPV16. We found that Six1 overexpression in HKc/HPV16 increased cell proliferation and promoted cell migration and invasion by inducing epithelial–mesenchymal transition (EMT). Moreover, the overexpression of Six1 in HKc/HPV16 resulted in resistance to serum and calcium-induced differentiation, which is the hallmark of the HKc/DR phenotype. Activation of MAPK in HKc/HPV16 overexpressing Six1 is linked to resistancemore » to calcium-induced differentiation. In conclusion, this study determined that Six1 overexpression resulted in differentiation resistance and promoted EMT at early stages of HPV16-mediated transformation of human keratinocytes. - Highlights: • Six1 expression increases during HPV16-mediated transformation. • Six1 overexpression causes differentiation resistance in HPV16-immortalized cells. • Six1 overexpression in HPV16-immortalized keratinocytes activates MAPK. • Activation of MAPK promotes EMT and differentiation resistance. • Six1 overexpression reduces Smad-dependent TGF-β signaling.« less

Proceedings of the 40th Lunar and Planetary Science Conference

NASA Technical Reports Server (NTRS)

2009-01-01

The 40th Lunar and Planetary Science Conference included sessions on: Phoenix: Exploration of the Martian Arctic; Origin and Early Evolution of the Moon; Comet Wild 2: Mineralogy and More; Astrobiology: Meteorites, Microbes, Hydrous Habitats, and Irradiated Ices; Phoenix: Soil, Chemistry, and Habitability; Planetary Differentiation; Presolar Grains: Structures and Origins; SPECIAL SESSION: Venus Atmosphere: Venus Express and Future Missions; Mars Polar Caps: Past and Present; SPECIAL SESSION: Lunar Missions: Results from Kaguya, Chang'e-1, and Chandrayaan-1, Part I; 5 Early Nebula Processes and Models; SPECIAL SESSION: Icy Satellites of Jupiter and Saturn: Cosmic Gymnasts; Mars: Ground Ice and Climate Change; SPECIAL SESSION: Lunar Missions: Results from Kaguya, Chang'e-1, and Chandrayaan-1, Part II; Chondrite Parent-Body Processes; SPECIAL SESSION: Icy Satellites of Jupiter and Saturn: Salubrious Surfaces; SNC Meteorites; Ancient Martian Crust: Primary Mineralogy and Aqueous Alteration; SPECIAL SESSION: Messenger at Mercury: A Global Perspective on the Innermost Planet; CAIs and Chondrules: Records of Early Solar System Processes; Small Bodies: Shapes of Things to Come; Sulfur on Mars: Rocks, Soils, and Cycling Processes; Mercury: Evolution and Tectonics; Venus Geology, Volcanism, Tectonics, and Resurfacing; Asteroid-Meteorite Connections; Impacts I: Models and Experiments; Solar Wind and Genesis: Measurements and Interpretation; Mars: Aqueous Processes; Magmatic Volatiles and Eruptive Conditions of Lunar Basalts; Comparative Planetology; Interstellar Matter: Origins and Relationships; Impacts II: Craters and Ejecta Mars: Tectonics and Dynamics; Mars Analogs I: Geological; Exploring the Diversity of Lunar Lithologies with Sample Analyses and Remote Sensing; Chondrite Accretion and Early History; Science Instruments for the Mars Science Lander; . Martian Gullies: Morphology and Origins; Mars: Dunes, Dust, and Wind; Mars: Volcanism; Early Solar System Chronology; Seek Out and Explore: Upcoming and Future Missions; Mars: Early History and Impact Processes; Mars Analogs II: Chemical and Spectral; Achondrites and their Parent Bodies; and Planning for Future Exploration of the Moon The poster sessions were: Lunar Missions: Results from Kaguya, Chang'e-1, and Chandrayaan-1; LRO and LCROSS; Geophysical Analysis of the Lunar Surface and Interior; Remote Observation and Geologic Mapping of the Lunar Surface; Lunar Spectroscopy; Venus Geology, Geophysics, Mapping, and Sampling; Planetary Differentiation; Bunburra and Buzzard Coulee: Recent Meteorite Falls; Meteorites: Terrestrial History; CAIs and Chondrules: Records of Early Solar System Processes; Volatile and Organic Compounds in Chondrites; Crashing Chondrites: Impact, Shock, and Melting; Ureilite Studies; Petrology and Mineralogy of the SNC Meteorites; Martian Meteorites; Phoenix Landing Site: Perchlorate and Other Tasty Treats; Mars Polar Atmospheres and Climate Modeling; Mars Polar Investigations; Mars Near-Surface Ice; Mars: A Volatile-Rich Planet; Mars: Geochemistry and Alteration Processes; Martian Phyllosilicates: Identification, Formation, and Alteration; Astrobiology; Instrument Concepts, Systems, and Probes for Investigating Rocks and Regolith; Seeing is Believing: UV, VIS, IR, X- and Gamma-Ray Camera and Spectrometer Instruments; Up Close and Personal: In Situ Analysis with Laser-Induced Breakdown Spectroscopy and Mass Spectrometry; Jupiter and Inscrutable Io; Tantalizing Titan; Enigmatic Enceladus and Intriguing Iapetus; Icy Satellites: Cryptic Craters; Icy Satellites: Gelid Geology/Geophysics; Icy Satellites: Cool Chemistry and Spectacular Spectroscopy; Asteroids and Comets; Comet Wild 2: Mineralogy and More; Hypervelocity Impacts: Stardust Models, LDEF, and ISPE; Presolar Grains; Early Nebular Processes: Models and Isotopes; Solar Wind and Genesis: Measurements and Interpretation; Education and Public Outreach; Mercury; Pursuing Lunar Exploration; Sources and Eruptionf Lunar Basalts; Chemical and Physical Properties of the Lunar Regolith; Lunar Dust and Transient Surface Phenomena; Lunar Databases and Data Restoration; Meteoritic Samples of the Moon; Chondrites, Their Clasts, and Alteration; Achondrites: Primitive and Not So Primitive; Iron Meteorites; Meteorite Methodology; Antarctic Micrometeorites; HEDs and Vesta; Dust Formation and Transformation; Interstellar Organic Matter; Early Solar System Chronology; Comparative Planetology; Impacts I: Models and Experiments; Impacts II: Craters and Ejecta; Mars: Volcanism; Mars: Tectonics and Dynamics; Martian Stratigraphy: Understanding the Geologic History of Mars Through the Sedimentary Rock Record; Mars: Valleys and Valley Networks; Mars: Aqueous Processes in Valles Marineris and the Southern Highlands; Mars: Aqueous Geomorphology; Martian Gullies: Morphology and Origins; Mars: Dunes, Dust, and Wind; Mars: Remote Sensing; Mars: Geologic Mapping, Photogrammetry, and Cratering; Martian Mineralogy: Constraints from Missions and Laboratory Investigations; Mars Analogs: Chemical and Physical; Mars Analogs: Sulfates and Sulfides; Missions: Approaches, Architectures, Analogs, and Actualities; Not Just Skin Deep: Electron Microscopy, Heat Flow, Radar, and Seismology Instruments and Planetary Data Systems, Techniques, and Interpretation.

Development of the earth-moon system with implications for the geology of the early earth

NASA Technical Reports Server (NTRS)

Smith, J. V.

1976-01-01

Established facts regarding the basic features of the earth and the moon are reviewed, and some important problems involving the moon are discussed (extent of melting, time of crustal differentiation and nature of bombardment, bulk chemical composition, and nature and source of mare basins), with attention given to the various existing theories concerning these problems. Models of the development of the earth-moon system from the solar nebula are examined, with particular attention focused on those that use the concept of capture with disintegration. Impact processes in the early crust of the earth are briefly considered, with attention paid to Green's (1972) suggestion that Archaean greenstone belts may be the terrestrial equivalent of lunar maria.

Antecedents and Outcomes of Joint Trajectories of Mother-Son Conflict and Warmth during Middle Childhood and Adolescence

PubMed Central

Trentacosta, Christopher J.; Criss, Michael M.; Shaw, Daniel S.; Lacourse, Eric; Hyde, Luke W.; Dishion, Thomas J.

2011-01-01

This study investigated the development of mother-son relationship quality from ages 5 to 15 in a sample of 265 low-income families. Non-parametric random effects modeling was utilized to uncover distinct and homogeneous developmental trajectories of conflict and warmth; antecedents and outcomes of the trajectory groups also were examined. Four conflict trajectory groups and three warmth trajectory groups were identified. Difficult temperament in early childhood discriminated both conflict and warmth trajectory group membership (TGM), and adult relationship quality in early childhood was related to warmth trajectories. In addition, conflict TGM differentiated youth antisocial behavior during adolescence, and warmth trajectories predicted adolescent peer relationship quality and youth moral disengagement. Implications for socialization processes are discussed. PMID:21883153

Fear conditioning and extinction across development: Evidence from human studies and animal models☆

PubMed Central

Shechner, Tomer; Hong, Melanie; Britton, Jennifer C.; Pine, Daniel S.; Fox, Nathan A.

2015-01-01

The ability to differentiate danger and safety through associative processes emerges early in life. Understanding the mechanisms underlying associative learning of threat and safety can clarify the processes that shape development of normative fears and pathological anxiety. Considerable research has used fear conditioning and extinction paradigms to delineate underlying mechanisms in animals and human adults; however, little is known about these mechanisms in children and adolescents. The current paper summarizes the empirical data on the development of fear conditioning and extinction. It reviews methodological considerations and future directions for research on fear conditioning and extinction in pediatric populations. PMID:24746848

RNA-sequencing of the sturgeon Acipenser baeri provides insights into expression dynamics of morphogenic differentiation and developmental regulatory genes in early versus late developmental stages.

PubMed

Song, Wei; Jiang, Keji; Zhang, Fengying; Lin, Yu; Ma, Lingbo

2016-08-08

Acipenser baeri, one of the critically endangered animals on the verge of extinction, is a key species for evolutionary, developmental, physiology and conservation studies and a standout amongst the most important food products worldwide. Though the transcriptome of the early development of A. baeri has been published recently, the transcriptome changes occurring in the transition from embryonic to late stages are still unknown. The aim of this work was to analyze the transcriptomes of embryonic and post-embryonic stages of A. baeri and identify differentially expressed genes (DEGs) and their expression patterns using mRNA collected from specimens at big yolk plug, wide neural plate and 64 day old sturgeon developmental stages for RNA-Seq. The paired-end sequencing of the transcriptome of samples of A. baeri collected at two early (big yolk plug (T1, 32 h after fertilization) and wide neural plate formation (T2, 45 h after fertilization)) and one late (T22, 64 day old sturgeon) developmental stages using Illumina Hiseq2000 platform generated 64039846, 64635214 and 75293762 clean paired-end reads for T1, T2 and T22, respectively. After quality control, the sequencing reads were de novo assembled to generate a set of 149,265 unigenes with N50 value of 1277 bp. Functional annotation indicated that a substantial number of these unigenes had significant similarity with proteins in public databases. Differential expression profiling allowed the identification of 2789, 12,819 and 10,824 DEGs from the respective T1 vs. T2, T1 vs. T22 and T2 vs. T22 comparisons. High correlation of DEGs' features was recorded among early stages while significant divergences were observed when comparing the late stage with early stages. GO and KEGG enrichment analyses revealed the biological processes, cellular component, molecular functions and metabolic pathways associated with identified DEGs. The qRT-PCR performed for candidate genes in specimens confirmed the validity of the RNA-seq data. This study presents, for the first time, an extensive overview of RNA-Seq based characterization of the early and post-embryonic developmental transcriptomes of A. baeri and provided 149,265 gene sequences that will be potentially valuable for future molecular and genetic studies in A. baeri.

Emotional Speech Perception Unfolding in Time: The Role of the Basal Ganglia

PubMed Central

Paulmann, Silke; Ott, Derek V. M.; Kotz, Sonja A.

2011-01-01

The basal ganglia (BG) have repeatedly been linked to emotional speech processing in studies involving patients with neurodegenerative and structural changes of the BG. However, the majority of previous studies did not consider that (i) emotional speech processing entails multiple processing steps, and the possibility that (ii) the BG may engage in one rather than the other of these processing steps. In the present study we investigate three different stages of emotional speech processing (emotional salience detection, meaning-related processing, and identification) in the same patient group to verify whether lesions to the BG affect these stages in a qualitatively different manner. Specifically, we explore early implicit emotional speech processing (probe verification) in an ERP experiment followed by an explicit behavioral emotional recognition task. In both experiments, participants listened to emotional sentences expressing one of four emotions (anger, fear, disgust, happiness) or neutral sentences. In line with previous evidence patients and healthy controls show differentiation of emotional and neutral sentences in the P200 component (emotional salience detection) and a following negative-going brain wave (meaning-related processing). However, the behavioral recognition (identification stage) of emotional sentences was impaired in BG patients, but not in healthy controls. The current data provide further support that the BG are involved in late, explicit rather than early emotional speech processing stages. PMID:21437277

Explicit attention interferes with selective emotion processing in human extrastriate cortex.

PubMed

Schupp, Harald T; Stockburger, Jessica; Bublatzky, Florian; Junghöfer, Markus; Weike, Almut I; Hamm, Alfons O

2007-02-22

Brain imaging and event-related potential studies provide strong evidence that emotional stimuli guide selective attention in visual processing. A reflection of the emotional attention capture is the increased Early Posterior Negativity (EPN) for pleasant and unpleasant compared to neutral images (approximately 150-300 ms poststimulus). The present study explored whether this early emotion discrimination reflects an automatic phenomenon or is subject to interference by competing processing demands. Thus, emotional processing was assessed while participants performed a concurrent feature-based attention task varying in processing demands. Participants successfully performed the primary visual attention task as revealed by behavioral performance and selected event-related potential components (Selection Negativity and P3b). Replicating previous results, emotional modulation of the EPN was observed in a task condition with low processing demands. In contrast, pleasant and unpleasant pictures failed to elicit increased EPN amplitudes compared to neutral images in more difficult explicit attention task conditions. Further analyses determined that even the processing of pleasant and unpleasant pictures high in emotional arousal is subject to interference in experimental conditions with high task demand. Taken together, performing demanding feature-based counting tasks interfered with differential emotion processing indexed by the EPN. The present findings demonstrate that taxing processing resources by a competing primary visual attention task markedly attenuated the early discrimination of emotional from neutral picture contents. Thus, these results provide further empirical support for an interference account of the emotion-attention interaction under conditions of competition. Previous studies revealed the interference of selective emotion processing when attentional resources were directed to locations of explicitly task-relevant stimuli. The present data suggest that interference of emotion processing by competing task demands is a more general phenomenon extending to the domain of feature-based attention. Furthermore, the results are inconsistent with the notion of effortlessness, i.e., early emotion discrimination despite concurrent task demands. These findings implicate to assess the presumed automatic nature of emotion processing at the level of specific aspects rather than considering automaticity as an all-or-none phenomenon.

Explicit attention interferes with selective emotion processing in human extrastriate cortex

PubMed Central

Schupp, Harald T; Stockburger, Jessica; Bublatzky, Florian; Junghöfer, Markus; Weike, Almut I; Hamm, Alfons O

2007-01-01

Background Brain imaging and event-related potential studies provide strong evidence that emotional stimuli guide selective attention in visual processing. A reflection of the emotional attention capture is the increased Early Posterior Negativity (EPN) for pleasant and unpleasant compared to neutral images (~150–300 ms poststimulus). The present study explored whether this early emotion discrimination reflects an automatic phenomenon or is subject to interference by competing processing demands. Thus, emotional processing was assessed while participants performed a concurrent feature-based attention task varying in processing demands. Results Participants successfully performed the primary visual attention task as revealed by behavioral performance and selected event-related potential components (Selection Negativity and P3b). Replicating previous results, emotional modulation of the EPN was observed in a task condition with low processing demands. In contrast, pleasant and unpleasant pictures failed to elicit increased EPN amplitudes compared to neutral images in more difficult explicit attention task conditions. Further analyses determined that even the processing of pleasant and unpleasant pictures high in emotional arousal is subject to interference in experimental conditions with high task demand. Taken together, performing demanding feature-based counting tasks interfered with differential emotion processing indexed by the EPN. Conclusion The present findings demonstrate that taxing processing resources by a competing primary visual attention task markedly attenuated the early discrimination of emotional from neutral picture contents. Thus, these results provide further empirical support for an interference account of the emotion-attention interaction under conditions of competition. Previous studies revealed the interference of selective emotion processing when attentional resources were directed to locations of explicitly task-relevant stimuli. The present data suggest that interference of emotion processing by competing task demands is a more general phenomenon extending to the domain of feature-based attention. Furthermore, the results are inconsistent with the notion of effortlessness, i.e., early emotion discrimination despite concurrent task demands. These findings implicate to assess the presumed automatic nature of emotion processing at the level of specific aspects rather than considering automaticity as an all-or-none phenomenon. PMID:17316444

HDAC1 and HDAC3 underlie dynamic H3K9 acetylation during embryonic neurogenesis and in schizophrenia-like animals.

PubMed

Večeřa, Josef; Bártová, Eva; Krejčí, Jana; Legartová, Soňa; Komůrková, Denisa; Rudá-Kučerová, Jana; Štark, Tibor; Dražanová, Eva; Kašpárek, Tomáš; Šulcová, Alexandra; Dekker, Frank J; Szymanski, Wiktor; Seiser, Christian; Weitzer, Georg; Mechoulam, Raphael; Micale, Vincenzo; Kozubek, Stanislav

2018-01-01

Although histone acetylation is one of the most widely studied epigenetic modifications, there is still a lack of information regarding how the acetylome is regulated during brain development and pathophysiological processes. We demonstrate that the embryonic brain (E15) is characterized by an increase in H3K9 acetylation as well as decreases in the levels of HDAC1 and HDAC3. Moreover, experimental induction of H3K9 hyperacetylation led to the overexpression of NCAM in the embryonic cortex and depletion of Sox2 in the subventricular ependyma, which mimicked the differentiation processes. Inducing differentiation in HDAC1-deficient mouse ESCs resulted in early H3K9 deacetylation, Sox2 downregulation, and enhanced astrogliogenesis, whereas neuro-differentiation was almost suppressed. Neuro-differentiation of (wt) ESCs was characterized by H3K9 hyperacetylation that was associated with HDAC1 and HDAC3 depletion. Conversely, the hippocampi of schizophrenia-like animals showed H3K9 deacetylation that was regulated by an increase in both HDAC1 and HDAC3. The hippocampi of schizophrenia-like brains that were treated with the cannabinoid receptor-1 inverse antagonist AM251 expressed H3K9ac at the level observed in normal brains. Together, the results indicate that co-regulation of H3K9ac by HDAC1 and HDAC3 is important to both embryonic brain development and neuro-differentiation as well as the pathophysiology of a schizophrenia-like phenotype. © 2017 Wiley Periodicals, Inc.

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.

A differential diagnosis of inherited endocrine tumors and their tumor counterparts

PubMed Central

Toledo, Sergio P. A.; Lourenço, Delmar M.; Toledo, Rodrigo A.

2013-01-01

Inherited endocrine tumors have been increasingly recognized in clinical practice, although some difficulties still exist in differentiating these conditions from their sporadic endocrine tumor counterparts. Here, we list the 12 main topics that could add helpful information and clues for performing an early differential diagnosis to distinguish between these conditions. The early diagnosis of patients with inherited endocrine tumors may be performed either clinically or by mutation analysis in at-risk individuals. Early detection usually has a large impact in tumor management, allowing preventive clinical or surgical therapy in most cases. Advice for the clinical and surgical management of inherited endocrine tumors is also discussed. In addition, recent clinical and genetic advances for 17 different forms of inherited endocrine tumors are briefly reviewed. PMID:23917672

Emerging self-regulation in toddlers born preterm or low birth weight: Differential susceptibility to parenting?

PubMed Central

POEHLMANN, JULIE; SCHWICHTENBERG, A. J. M.; SHLAFER, REBECCA J.; HAHN, EMILY; BIANCHI, JON-PAUL; WARNER, RACHAEL

2012-01-01

The differential susceptibility to parenting model was examined in relation to toddler self-regulation in a prospective longitudinal study of infants born preterm or low birth weight. We followed 153 mother–infant dyads across five time points between the infant’s Neonatal Intensive Care Unit stay and 24 months postterm. Assessments of infant temperament, quality of early parenting interactions, contextual variables, and toddler effortful control and behavior problems were conducted. Results supported differential susceptibility and dual risk models in addition to documenting main effects of early parenting on children’s emerging self-regulation. Our data suggested that preterm or low birth weight infants who were prone to distress or rated by mothers as more difficult were particularly susceptible to the effects of early negative parenting. PMID:21262047

Antagonism between the transcription factors NANOG and OTX2 specifies rostral or caudal cell fate during neural patterning transition.

PubMed

Su, Zhenghui; Zhang, Yanqi; Liao, Baojian; Zhong, Xiaofen; Chen, Xin; Wang, Haitao; Guo, Yiping; Shan, Yongli; Wang, Lihui; Pan, Guangjin

2018-03-23

During neurogenesis, neural patterning is a critical step during which neural progenitor cells differentiate into neurons with distinct functions. However, the molecular determinants that regulate neural patterning remain poorly understood. Here we optimized the "dual SMAD inhibition" method to specifically promote differentiation of human pluripotent stem cells (hPSCs) into forebrain and hindbrain neural progenitor cells along the rostral-caudal axis. We report that neural patterning determination occurs at the very early stage in this differentiation. Undifferentiated hPSCs expressed basal levels of the transcription factor orthodenticle homeobox 2 (OTX2) that dominantly drove hPSCs into the "default" rostral fate at the beginning of differentiation. Inhibition of glycogen synthase kinase 3β (GSK3β) through CHIR99021 application sustained transient expression of the transcription factor NANOG at early differentiation stages through Wnt signaling. Wnt signaling and NANOG antagonized OTX2 and, in the later stages of differentiation, switched the default rostral cell fate to the caudal one. Our findings have uncovered a mutual antagonism between NANOG and OTX2 underlying cell fate decisions during neural patterning, critical for the regulation of early neural development in humans. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Early Childhood Stuttering and Electrophysiological Indices of Language Processing

PubMed Central

Weber-Fox, Christine; Wray, Amanda Hampton; Arnold, Hayley

2013-01-01

We examined neural activity mediating semantic and syntactic processing in 27 preschool-age children who stutter (CWS) and 27 preschool-age children who do not stutter (CWNS) matched for age, nonverbal IQ and language abilities. All participants displayed language abilities and nonverbal IQ within the normal range. Event-related brain potentials (ERPs) were elicited while participants watched a cartoon video and heard naturally spoken sentences that were either correct or contained semantic or syntactic (phrase structure) violations. ERPs in CWS, compared to CWNS, were characterized by longer N400 peak latencies elicited by semantic processing. In the CWS, syntactic violations elicited greater negative amplitudes for the early time window (150–350 ms) over medial sites compared to CWNS. Additionally, the amplitude of the P600 elicited by syntactic violations relative to control words was significant over the left hemisphere for the CWNS but showed the reverse pattern in CWS, a robust effect only over the right hemisphere. Both groups of preschoolage children demonstrated marked and differential effects for neural processes elicited by semantic and phrase structure violations; however, a significant proportion of young CWS exhibit differences in the neural functions mediating language processing compared to CWNS despite normal language abilities. These results are the first to show that differences in event-related brain potentials reflecting language processing occur as early as the preschool years in CWS and provide the first evidence that atypical lateralization of hemispheric speech/language functions previously observed in the brains of adults who stutter begin to emerge near the onset of developmental stuttering. PMID:23773672

[Effective size of the early-run sockeye salmon Oncorhynchus nerka population of Lake Azabach'e, Kamchatka Peninsula evaluation of the effect of interaction between subpopulations within a subdivided population].

PubMed

Efremov, V V

2005-05-01

The effect of subdivision on the effective size (Ne) of the early-run sockeye salmon Oncorhynchus nerka population of Lake Azabach'e (Kamchatka Peninsula) has been studied. The mode of this effect is determined by the relative productivity of the subpopulations and its magnitude, by the rate of individual migration among subpopulations and genetic differentiation. If the contributions of subpopulations (offspring numbers) are different, genetic differentiation can reduce the Ne of the subdivided population. At equal subpopulation contributions, genetic differentiation always increases the Ne of the subdivided population in comparison with a panmictic population. We have found that all sockeye salmon subpopulations of Azabach'e Lake produce equal offspring numbers contributing to the next generation. The genetic differentiation between sockeye salmon subpopulations is low, and the subdivision increases the Ne of the early-run race with reference to the sum of the effective sizes of the subpopulations by as little as 2%.

Maternal effects and Symbiodinium community composition drive differential patterns in juvenile survival in the coral Acropora tenuis

PubMed Central

Willis, Bette L.; Bay, Line K.

2016-01-01

Coral endosymbionts in the dinoflagellate genus Symbiodinium are known to impact host physiology and have led to the evolution of reef-building, but less is known about how symbiotic communities in early life-history stages and their interactions with host parental identity shape the structure of coral communities on reefs. Differentiating the roles of environmental and biological factors driving variation in population demographic processes, particularly larval settlement, early juvenile survival and the onset of symbiosis is key to understanding how coral communities are structured and to predicting how they are likely to respond to climate change. We show that maternal effects (that here include genetic and/or effects related to the maternal environment) can explain nearly 24% of variation in larval settlement success and 5–17% of variation in juvenile survival in an experimental study of the reef-building scleractinian coral, Acropora tenuis. After 25 days on the reef, Symbiodinium communities associated with juvenile corals differed significantly between high mortality and low mortality families based on estimates of taxonomic richness, composition and relative abundance of taxa. Our results highlight that maternal and familial effects significantly explain variation in juvenile survival and symbiont communities in a broadcast-spawning coral, with Symbiodinium type A3 possibly a critical symbiotic partner during this early life stage. PMID:27853562

Nailfold Capillaroscopy Within and Beyond the Scope of Connective Tissue Diseases.

PubMed

Lambova, Sevdalina Nikolova; Muller-Ladner, Ulf

2018-04-20

Nailfold capillaroscopy is a noninvasive instrumental method for morphological analysis of the nutritive capillaries in the nailfold area. In rheumatology, it is a method of choice among instrumental modalities for differential diagnosis between primary and secondary Raynaud's phenomenon (RP) in systemic rheumatic diseases. RP is a common diagnostic problem in rheumatology. Defining the proper diagnosis is a prerequisite for administration of the appropriate treatment. Thus, nailfold capillaroscopic examination is of crucial importance for the every-day practice of the rheumatologists and is currently gaining increasing attention. The most specific capillaroscopic changes are observed in Systemic Sclerosis (SSc). Due to the high prevalence of the capillaroscopic changes in this clinical entity and their early appearance, they could be used for early and very early diagnosis of the disease. More recently, "scleroderma" type capillaroscopic changes have been defined as diagnostic criterion in the new EULAR/ACR classification criteria for SSc together with the presence of scleroderma-related autoantibodies, RP, telangiectasia and other clinical signs. Capillaroscopic changes in other connective tissue diseases and in different rheumatic-like conditions like those in diabetes mellitus (e.g., diabetic stiff-hand syndrome) and paraneoplastic syndromes associated with microvascular pathology should be interpreted properly in order to obtain precise diagnosis in the shortest possible differential diagnostic process. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Laser Raman detection for oral cancer based on an adaptive Gaussian process classification method with posterior probabilities

NASA Astrophysics Data System (ADS)

Du, Zhanwei; Yang, Yongjian; Bai, Yuan; Wang, Lijun; Su, Le; Chen, Yong; Li, Xianchang; Zhou, Xiaodong; Jia, Jun; Shen, Aiguo; Hu, Jiming

2013-03-01

The existing methods for early and differential diagnosis of oral cancer are limited due to the unapparent early symptoms and the imperfect imaging examination methods. In this paper, the classification models of oral adenocarcinoma, carcinoma tissues and a control group with just four features are established by utilizing the hybrid Gaussian process (HGP) classification algorithm, with the introduction of the mechanisms of noise reduction and posterior probability. HGP shows much better performance in the experimental results. During the experimental process, oral tissues were divided into three groups, adenocarcinoma (n = 87), carcinoma (n = 100) and the control group (n = 134). The spectral data for these groups were collected. The prospective application of the proposed HGP classification method improved the diagnostic sensitivity to 56.35% and the specificity to about 70.00%, and resulted in a Matthews correlation coefficient (MCC) of 0.36. It is proved that the utilization of HGP in LRS detection analysis for the diagnosis of oral cancer gives accurate results. The prospect of application is also satisfactory.

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

PubMed Central

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

2015-01-01

Human bone marrow stromal cells (hBMSCs, also known as bone marrow-derived mesenchymal stem cells) are a population of progenitor cells that contain a subset of skeletal stem cells (hSSCs), able to recreate cartilage, bone, stroma that supports hematopoiesis and marrow adipocytes. As such, they have become an important resource in developing strategies for regenerative medicine and tissue engineering due to their self-renewal and differentiation capabilities. The differentiation of SSCs/BMSCs is dependent on exposure to biophysical and biochemical stimuli that favor early and rapid activation of the in vivo tissue repair process. Exposure to exogenous stimuli such as an electromagnetic field (EMF) can promote differentiation of SSCs/BMSCs via ion dynamics and small signaling molecules. The plasma membrane is often considered to be the main target for EMF signals and most results point to an effect on the rate of ion or ligand binding due to a receptor site acting as a modulator of signaling cascades. Ion fluxes are closely involved in differentiation control as stem cells move and grow in specific directions to form tissues and organs. EMF affects numerous biological functions such as gene expression, cell fate, and cell differentiation, but will only induce these effects within a certain range of low frequencies as well as low amplitudes. EMF has been reported to be effective in the enhancement of osteogenesis and chondrogenesis of hSSCs/BMSCs with no documented negative effects. Studies show specific EMF frequencies enhance hSSC/BMSC adherence, proliferation, differentiation, and viability, all of which play a key role in the use of hSSCs/BMSCs for tissue engineering. While many EMF studies report significant enhancement of the differentiation process, results differ depending on the experimental and environmental conditions. Here we review how specific EMF parameters (frequency, intensity, and time of exposure) significantly regulate hSSC/BMSC differentiation in vitro. We discuss optimal conditions and parameters for effective hSSC/BMSC differentiation using EMF treatment in an in vivo setting, and how these can be translated to clinical trials. PMID:26042793

Enhancer and Transcription Factor Dynamics during Myeloid Differentiation Reveal an Early Differentiation Block in Cebpa null Progenitors.

PubMed

Pundhir, Sachin; Bratt Lauridsen, Felicia Kathrine; Schuster, Mikkel Bruhn; Jakobsen, Janus Schou; Ge, Ying; Schoof, Erwin Marten; Rapin, Nicolas; Waage, Johannes; Hasemann, Marie Sigurd; Porse, Bo Torben

2018-05-29

Transcription factors PU.1 and CEBPA are required for the proper coordination of enhancer activity during granulocytic-monocytic (GM) lineage differentiation to form myeloid cells. However, precisely how these factors control the chronology of enhancer establishment during differentiation is not known. Through integrated analyses of enhancer dynamics, transcription factor binding, and proximal gene expression during successive stages of murine GM-lineage differentiation, we unravel the distinct kinetics by which PU.1 and CEBPA coordinate GM enhancer activity. We find no evidence of a pioneering function of PU.1 during late GM-lineage differentiation. Instead, we delineate a set of enhancers that gain accessibility in a CEBPA-dependent manner, suggesting a pioneering function of CEBPA. Analyses of Cebpa null bone marrow demonstrate that CEBPA controls PU.1 levels and, unexpectedly, that the loss of CEBPA results in an early differentiation block. Taken together, our data provide insights into how PU.1 and CEBPA functionally interact to drive GM-lineage differentiation. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Sexual differentiation of the human brain: relation to gender identity, sexual orientation and neuropsychiatric disorders.

PubMed

Bao, Ai-Min; Swaab, Dick F

2011-04-01

During the intrauterine period a testosterone surge masculinizes the fetal brain, whereas the absence of such a surge results in a feminine brain. As sexual differentiation of the brain takes place at a much later stage in development than sexual differentiation of the genitals, these two processes can be influenced independently of each other. Sex differences in cognition, gender identity (an individual's perception of their own sexual identity), sexual orientation (heterosexuality, homosexuality or bisexuality), and the risks of developing neuropsychiatric disorders are programmed into our brain during early development. There is no evidence that one's postnatal social environment plays a crucial role in gender identity or sexual orientation. We discuss the relationships between structural and functional sex differences of various brain areas and the way they change along with any changes in the supply of sex hormones on the one hand and sex differences in behavior in health and disease on the other. Copyright © 2011 Elsevier Inc. All rights reserved.

Cortical pitch response components show differential sensitivity to native and nonnative pitch contours

PubMed Central

Krishnan, Ananthanarayan; Gandour, Jackson T.; Suresh, Chandan H.

2015-01-01

The aim of this study is to evaluate how nonspeech pitch contours of varying shape influence latency and amplitude of cortical pitch-specific response (CPR) components differentially as a function of language experience. Stimuli included time-varying, high rising Mandarin Tone 2 (T2) and linear rising ramp (Linear), and steady-state (Flat). Both the latency and magnitude of CPR components were differentially modulated by (i) the overall trajectory of pitch contours (time-varying vs. steady-state), (ii) their pitch acceleration rates (changing vs. constant), and (iii) their linguistic status (lexical vs. non-lexical). T2 elicited larger amplitude than Linear in both language groups, but size of the effect was larger in Chinese than English. The magnitude of CPR components elicited by T2 were larger for Chinese than English at the right temporal electrode site. Using the CPR, we provide evidence in support of experience-dependent modulation of dynamic pitch contours at an early stage of sensory processing. PMID:25306506

Transcriptome analysis of dorsal root ganglia's diabetic neuropathy reveals mechanisms involved in pain and regeneration.

PubMed

Athie, Maria Carolina Pedro; Vieira, Andre Schwambach; Teixeira, Juliana Maia; Dos Santos, Gilson Gonçalves; Dias, Elayne Vieira; Tambeli, Claudia Herrera; Sartori, Cesar Renato; Parada, Carlos A

2018-05-08

Peripheral diabetic neuropathy (DN) manifests in nearly 60% of diabetic patients, being pain its most debilitating symptom. Although electrophysiological and morphological aspects are well described, little is known about its development and progression, undermining effective therapies. Hyperglycemia and insulin signaling impairment are considered the triggering events of oxidative stress observed in the dying nerves, however there are still many gaps in the knowledge of intracellular plastic changes it generates. In this study we aimed to evaluate the early transcriptome changes in DN when the first symptoms of the disease start to appear. Next-Generation Sequencing of messenger RNA (RNA-Seq) of L4 and L5 dorsal root ganglia (DRG) four weeks post-diabetes induction in a rat model for type 1 diabetes. RNA sequencing found 66 transcripts differentially expressed between diabetic and control groups, related mainly to the following biological processes: inflammation, hyperalgesia/analgesia, cell growth and cell survival. Given their roles, the differentially expressed genes suggest an attempt to switch to a survival/regenerative program. Our results show that changes in the transcriptome profile start to appear early in the course of DN and might be related to secure cell homeostasis. Hence, the present data may indicate how DRG cells are responding to hyperglycemia in its early stages and which mechanisms first fail to respond, further leading to cell damage and cell death. Early screening of cell alterations in DN might lead to more concrete targets for pharmaceutical interventions, which could more efficiently delay cell damage. Copyright © 2017. Published by Elsevier Inc.

Effect of oxygen plasma etching on pore size-controlled 3D polycaprolactone scaffolds for enhancing the early new bone formation in rabbit calvaria.

PubMed

Kook, Min-Suk; Roh, Hee-Sang; Kim, Byung-Hoon

2018-05-02

This study was to investigate the effects of O 2 plasma-etching of the 3D polycaprolactone (PCL) scaffold surface on preosteoblast cell proliferation and differentiation, and early new bone formation. The PCL scaffolds were fabricated by 3D printing technique. After O 2 plasma treatment, surface characterizations were examined by scanning electron microscopy, atomic force microscopy, and contact angle. MTT assay was used to determine cell proliferation. To investigate the early new bone formation, rabbits were sacrificed at 2 weeks for histological analyses. As the O 2 plasma etching time is increased, roughness and hydrophilicity of the PCL scaffold surface increased. The cell proliferation and differentiation on plasma-etched samples was significantly increased than on untreated samples. At 2 weeks, early new bone formation in O 2 plasma-etched PCL scaffolds was the higher than that of untreated scaffolds. The O 2 plasma-etched PCL scaffolds showed increased preosteoblast differentiation as well as increased new bone formation.

Convergent Validity of the Mullen Scales of Early Learning and the Differential Ability Scales in Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Bishop, Somer L.; Guthrie, Whitney; Coffing, Mia; Lord, Catherine

2011-01-01

Despite widespread use of the Mullen Scales of Early Learning (MSEL; E. M. Mullen, 1995) as a cognitive test for children with autism spectrum disorders and other developmental disabilities, the instrument has not been independently validated for use in these populations. Convergent validity of the MSEL and the Differential Ability Scales (DAS; C.…

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

PubMed Central

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

2014-01-01

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

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.

Global processing in amblyopia: a review

PubMed Central

Hamm, Lisa M.; Black, Joanna; Dai, Shuan; Thompson, Benjamin

2014-01-01

Amblyopia is a neurodevelopmental disorder of the visual system that is associated with disrupted binocular vision during early childhood. There is evidence that the effects of amblyopia extend beyond the primary visual cortex to regions of the dorsal and ventral extra-striate visual cortex involved in visual integration. Here, we review the current literature on global processing deficits in observers with either strabismic, anisometropic, or deprivation amblyopia. A range of global processing tasks have been used to investigate the extent of the cortical deficit in amblyopia including: global motion perception, global form perception, face perception, and biological motion. These tasks appear to be differentially affected by amblyopia. In general, observers with unilateral amblyopia appear to show deficits for local spatial processing and global tasks that require the segregation of signal from noise. In bilateral cases, the global processing deficits are exaggerated, and appear to extend to specialized perceptual systems such as those involved in face processing. PMID:24987383

Effects of administration of a proton pump inhibitor before endoscopic submucosal dissection for differentiated early gastric cancer with ulcer.

PubMed

Myung, Yu Sik; Hong, Su Jin; Han, Jae Pil; Park, Kyung Woo; Ko, Bong Min; Lee, Moon Sung

2017-01-01

In ulcerative early gastric cancer, improvement and exacerbation of ulceration repeat as a malignant cycle. Moreover, early gastric cancer combined with ulcer is associated with a low curative resection rate and high risk of adverse events. The aim of this study was to investigate the ulcer healing rate and clinical outcomes with the administration of a proton pump inhibitor before endoscopic submucosal dissection for differentiated early gastric cancer with ulcer. A total of 136 patients with differentiated early gastric cancer with ulcer who met the expanded indications for endoscopic submucosal dissection were reviewed between June 2005 and June 2014. Eighty-one patients were given PPI before endoscopic submucosal dissection and 55 patients were not given PPI. The complete ulcer healing rate was significantly different between the two groups (59.3 % vs. 23.6 %, P < 0.001). The procedure time was 38.1 ± 35.7 and 50.8 ± 50.2 min (P = 0.047). However, no significant differences were detected in the en bloc resection rate, complete resection rate, and adverse events including bleeding and perforation. Multivariate analysis showed that administration of PPI (OR = 10.83, P < 0.001) and mucosal invasion (OR = 24.43, P < 0.001) were independent factors that predicted complete healing of ulceration. The calculated accuracy for whether complete healing of the ulcer after PPI administration can differentiate mucosal from submucosal invasion was 75.3 %. Administration of PPI before ESD in differentiated EGC meeting the expanded criteria is effective to heal the ulcer lesion and reduce the mean procedure time. Complete healing of the ulcer after PPI administration suggests mucosal cancer.

Influence of thyroid in nervous system growth.

PubMed

Mussa, G C; Mussa, F; Bretto, R; Zambelli, M C; Silvestro, L

2001-08-01

Nervous system growth and differentiation are closely correlated with the presence of iodine and thyroid hormones in initial development stages. In the human species, encephalon maturation during the first quarter of pregnancy is affected according to recent studies by the transplacenta passage of maternal thyroid hormones while it depends on initial iodiothyronin secretion by the foetal gland after the 12th week of pregnancy. Thyroid hormone deficiency during nervous system development causes altered noble nervous cells, such as the pyramidal cortical and Purkinje cells, during glial cell proliferation and differentiation alike. Neurons present cell hypoplasia with reduced axon count, dendritic branching, synaptic spikes and interneuron connections. Oligodendrocytes decrease in number and average myelin content consequently drops. Biochemical studies on hypothyroid rats have demonstrated alterations to neuron intraplasmatic microtubule content and organisation, changed mitochondria number and arrangement and anomalies in T3 nuclear and citoplasmatic receptor maturation. Alterations to microtubules are probably responsible for involvement of the axon-dendrite system, and are the consequence of deficient thyroid hormone action on the mitochondria, the mitochondria enzymes and proteins associated with microtubules. Nuclear and citoplasmatic receptors have been identified and gene clonation studies have shown two families of nuclear receptors that include several sub-groups in their turn. A complex scheme of temporal and spatial expression of these receptors exists, so they probably contribute with one complementary function, although their physiological role differs. The action of thyroid hormones occurs by changing cell protein levels because of their regulation at the transcriptional or post-transcriptional level. Genes submitted to thyroid hormone control are either expressed by oligodendrytes, which are myelin protein coders or glial differentiation mediators, or are nervous cell specific, genes coding neurotropins or proteins involved in synaptic excitation. The use of new PMRS and MRI non-invasive techniques has enabled identification of metabolic and biochemical markers for alterations in the encephalon of untreated hypothyroid children. Even an excess of thyroid hormones during early nervous system development can cause permanent effects. Hyperthyroidism in fact initially induces accelerated maturation process including cell migration and differentiation, extension of dendritic processes and synaptogenesis but a later excess of thyroid hormones causes reduction of the total number of dendritic spikes, due to early interruption of neuron proliferation. Experimental studies and clinical research have clarified not only the correlation between nervous system maturation and thyroid function during early development stages and the certain finding from this research is that both excess and deficient thyroid hormones can cause permanent anatomo-functional alterations to the nervous system.

Mapping of Brain Activity by Automated Volume Analysis of Immediate Early Genes.

PubMed

Renier, Nicolas; Adams, Eliza L; Kirst, Christoph; Wu, Zhuhao; Azevedo, Ricardo; Kohl, Johannes; Autry, Anita E; Kadiri, Lolahon; Umadevi Venkataraju, Kannan; Zhou, Yu; Wang, Victoria X; Tang, Cheuk Y; Olsen, Olav; Dulac, Catherine; Osten, Pavel; Tessier-Lavigne, Marc

2016-06-16

Understanding how neural information is processed in physiological and pathological states would benefit from precise detection, localization, and quantification of the activity of all neurons across the entire brain, which has not, to date, been achieved in the mammalian brain. We introduce a pipeline for high-speed acquisition of brain activity at cellular resolution through profiling immediate early gene expression using immunostaining and light-sheet fluorescence imaging, followed by automated mapping and analysis of activity by an open-source software program we term ClearMap. We validate the pipeline first by analysis of brain regions activated in response to haloperidol. Next, we report new cortical regions downstream of whisker-evoked sensory processing during active exploration. Last, we combine activity mapping with axon tracing to uncover new brain regions differentially activated during parenting behavior. This pipeline is widely applicable to different experimental paradigms, including animal species for which transgenic activity reporters are not readily available. Copyright © 2016 Elsevier Inc. All rights reserved.

Mapping of brain activity by automated volume analysis of immediate early genes

PubMed Central

Renier, Nicolas; Adams, Eliza L.; Kirst, Christoph; Wu, Zhuhao; Azevedo, Ricardo; Kohl, Johannes; Autry, Anita E.; Kadiri, Lolahon; Venkataraju, Kannan Umadevi; Zhou, Yu; Wang, Victoria X.; Tang, Cheuk Y.; Olsen, Olav; Dulac, Catherine; Osten, Pavel; Tessier-Lavigne, Marc

2016-01-01

Summary Understanding how neural information is processed in physiological and pathological states would benefit from precise detection, localization and quantification of the activity of all neurons across the entire brain, which has not to date been achieved in the mammalian brain. We introduce a pipeline for high speed acquisition of brain activity at cellular resolution through profiling immediate early gene expression using immunostaining and light-sheet fluorescence imaging, followed by automated mapping and analysis of activity by an open-source software program we term ClearMap. We validate the pipeline first by analysis of brain regions activated in response to Haloperidol. Next, we report new cortical regions downstream of whisker-evoked sensory processing during active exploration. Lastly, we combine activity mapping with axon tracing to uncover new brain regions differentially activated during parenting behavior. This pipeline is widely applicable to different experimental paradigms, including animal species for which transgenic activity reporters are not readily available. PMID:27238021

TSH Receptor Function Is Required for Normal Thyroid Differentiation in Zebrafish

PubMed Central

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

2011-01-01

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

Zebrafish sex: a complicated affair

PubMed Central

Liew, Woei Chang

2014-01-01

In this review, we provide a detailed overview of studies on the elusive sex determination (SD) and gonad differentiation mechanisms of zebrafish (Danio rerio). We show that the data obtained from most studies are compatible with polygenic sex determination (PSD), where the decision is made by the allelic combinations of several loci. These loci are typically dispersed throughout the genome, but in some teleost species a few of them might be located on a preferential pair of (sex) chromosomes. The PSD system has a much higher level of variation of SD genotypes both at the level of gametes and the sexual genotype of individuals, than that of the chromosomal sex determination systems. The early sexual development of zebrafish males is a complicated process, as they first develop a ‘juvenile ovary’, that later undergoes a transformation to give way to a testis. To date, three major developmental pathways were shown to be involved with gonad differentiation through the modulation of programmed cell death. In our opinion, there are more pathways participating in the regulation of zebrafish gonad differentiation/transformation. Introduction of additional powerful large-scale genomic approaches into the analysis of zebrafish reproduction will result in further deepening of our knowledge as well as identification of additional pathways and genes associated with these processes in the near future. PMID:24148942

Prion potency in stem cells biology.

PubMed

Lopes, Marilene H; Santos, Tiago G

2012-01-01

Prion protein (PrP) can be considered a pivotal molecule because it interacts with several partners to perform a diverse range of critical biological functions that might differ in embryonic and adult cells. In recent years, there have been major advances in elucidating the putative role of PrP in the basic biology of stem cells in many different systems. Here, we review the evidence indicating that PrP is a key molecule involved in driving different aspects of the potency of embryonic and tissue-specific stem cells in self-perpetuation and differentiation in many cell types. It has been shown that PrP is involved in stem cell self-renewal, controlling pluripotency gene expression, proliferation, and neural and cardiomyocyte differentiation. PrP also has essential roles in distinct processes that regulate tissue-specific stem cell biology in nervous and hematopoietic systems and during muscle regeneration. Results from our own investigations have shown that PrP is able to modulate self-renewal and proliferation in neural stem cells, processes that are enhanced by PrP interactions with stress inducible protein 1 (STI1). Thus, the available data reveal the influence of PrP in acting upon the maintenance of pluripotent status or the differentiation of stem cells from the early embryogenesis through adulthood.

Evidence for an anterior-posterior differentiation in the human hippocampal formation revealed by meta-analytic parcellation of fMRI coordinate maps: focus on the subiculum.

PubMed

Chase, Henry W; Clos, Mareike; Dibble, Sofia; Fox, Peter; Grace, Anthony A; Phillips, Mary L; Eickhoff, Simon B

2015-06-01

Previous studies, predominantly in experimental animals, have suggested the presence of a differentiation of function across the hippocampal formation. In rodents, ventral regions are thought to be involved in emotional behavior while dorsal regions mediate cognitive or spatial processes. Using a combination of modeling the co-occurrence of significant activations across thousands of neuroimaging experiments and subsequent data-driven clustering of these data we were able to provide evidence of distinct subregions within a region corresponding to the human subiculum, a critical hub within the hippocampal formation. This connectivity-based model consists of a bilateral anterior region, as well as separate posterior and intermediate regions on each hemisphere. Functional connectivity assessed both by meta-analytic and resting fMRI approaches revealed that more anterior regions were more strongly connected to the default mode network, and more posterior regions were more strongly connected to 'task positive' regions. In addition, our analysis revealed that the anterior subregion was functionally connected to the ventral striatum, midbrain and amygdala, a circuit that is central to models of stress and motivated behavior. Analysis of a behavioral taxonomy provided evidence for a role for each subregion in mnemonic processing, as well as implication of the anterior subregion in emotional and visual processing and the right posterior subregion in reward processing. These findings lend support to models which posit anterior-posterior differentiation of function within the human hippocampal formation and complement other early steps toward a comparative (cross-species) model of the region. Copyright © 2015 Elsevier Inc. All rights reserved.

Some further observations and comments on the earliest role of the father.

PubMed

Abelin, E L

1975-08-01

The longitudinal observation in the family setting of a boy (Michael) during his first two years is used to explore further the earliest role of the father, and to refine my 'early triangulation' model. This model was meant to account for some basic phenomena of Mahler's rapprochement subphase, and was partly based on Piaget's framework. The data are presented along three developmental lines. (1) The specific relationship with father as a different person: the concepts of 'specific refuelling' and of object-specific libido are introduced; and it is suggested that during the subphase of differentiation, all of Michael's specific objects (in particular, the father) shared some 'symbiotic' quality with the mother. (2) On the other hand, qualitative differences of the father relationship were also noted; they confirmed my earlier findings and Mahler's view. (3) Very early, Michael began to acknowledge the relationship with the parents as a couple. After a fleeting indication of rivalry (with mother!), a ritual game of 'getting his parents together' developed at the onset of the rapprochement subphase. This is discussed as one of many possible compromise solutions to avoid the full achievement of the anxiety-provoking 'early triangulation' process. This process, if completed, would involve 'identification with the rival parent', formation of a mental image of the self, and the positive cathexis of neutralized intragroup relationships (which presupposes symbolization). The ubiquitous observation of 'identification with the rival baby' may represent another such compromise solution, and thus a precursor of early triangulation. It might also be a parellel process, leading to 'generational identification' as distinguished from 'gender identification'. The isomorphism of these processes with Piaget's outline of cognitive development is pointed out.

Autofluorescence endoscopy with "real-time" digital image processing in differential diagnostics of selected benign and malignant lesions in the oesophagus.

PubMed

Sieroń-Stołtny, Karolina; Kwiatek, Sebastian; Latos, Wojciech; Kawczyk-Krupka, Aleksandra; Cieślar, Grzegorz; Stanek, Agata; Ziaja, Damian; Bugaj, Andrzej M; Sieroń, Aleksander

2012-03-01

Oesophageal papilloma and Barrett's oesophagus are benign lesions known as risk factors of carcinoma in the oesophagus. Therefore, it is important to diagnose these early changes before neoplastic transformation. Autofluorescence endoscopy is a fast and non-invasive method of imaging of tissues based on the natural fluorescence of endogenous fluorophores. The aim of this study was to prove the diagnostic utility of autofluorescence endoscopy with digital image processing in histological diagnosis of endoscopic findings in the upper digestive tract, primarily in the imaging of oesophageal papilloma. During the retrospective analysis of about 200 endoscopic procedures in the upper digestive tract, 67 cases of benign, precancerous or cancerous changes were found. White light endoscopy (WLE) image, single-channel (red or green) autofluorescence images, as well as green and red fluorescence intensities in two modal fluorescence image and red-to-green (R/G) ratio (Numerical Colour Value, NCV) were correlated with histopathologic results. The NCV analysis in autofluorescence imaging (AFI) showed increased R/G ratio in cancerous changes in 96% vs. 85% in WLE. Simultaneous analysis with digital image processing allowed us to diagnose suspicious tissue as cancerous in all of cases. Barrett's metaplasia was confirmed in 90% vs. 79% (AFI vs. WLE), and 98% in imaging with digital image processing. In benign lesions, WLE allowed us to exclude tissue as malignant in 85%. Using autofluorescence endoscopy R/G ratio was increased in only 10% of benign changes causing the picture to be interpreted as suspicious, but when both methods were used together, 97.5% were cases excluded as malignancies. Mean R/G ratios were estimated to be 2.5 in cancers, 1.25 in Barrett's metaplasia and 0.75 in benign changes and were statistically significant (p=0.04). Autofluorescence imaging is a sensitive method to diagnose precancerous and cancerous early stages of the diseases located in oesophagus. Especially in two-modal imaging including white light endoscopy, autofluorescence imaging with digital image processing seems to be a useful modality of early diagnostics. Also in observation of papilloma changes, it facilitates differentiation between neoplastic and benign lesions and more accurate estimation of the risk of potential malignancy. Copyright © 2011 Elsevier B.V. All rights reserved.

Role of the POZ zinc finger transcription factor FBI-1 in human and murine adipogenesis.

PubMed

Laudes, Matthias; Christodoulides, Constantinos; Sewter, Ciaran; Rochford, Justin J; Considine, Robert V; Sethi, Jaswinder K; Vidal-Puig, Antonio; O'Rahilly, Stephen

2004-03-19

Poxvirus zinc finger (POZ) zinc finger domain transcription factors have been shown to play a role in the control of growth arrest and differentiation in several types of mesenchymal cells but not, as yet, adipocytes. We found that a POZ domain protein, factor that binds to inducer of short transcripts-1 (FBI-1), was induced during both murine and human preadipocyte differentiation with maximal expression levels seen at days 2-4. FBI-1 mRNA was expressed in human adipose tissue with the highest levels found in samples from morbidly obese subjects. Murine cell lines constitutively expressing FBI-1 showed evidence for accelerated adipogenesis with earlier induction of markers of differentiation and enhanced lipid accumulation, suggesting that FBI-1 may be an active participant in the differentiation process. Consistent with the properties of this family of proteins in other cell systems, 3T3L1 cells stably overexpressing FBI-1 showed reduced DNA synthesis and reduced expression of cyclin A, cyclin-dependent kinase 2, and p107, proteins known to be involved in the regulation of mitotic clonal expansion. In addition, FBI-1 reduced the transcriptional activity of the cyclin A promoter. Thus, FBI-1, a POZ zinc finger transcription factor, is induced during the early phases of human and murine preadipocyte differentiation where it may contribute to adipogenesis through influencing the switch from cellular proliferation to terminal differentiation.

DD-RT-PCR identifies 7-dehydrocholesterol reductase as a key marker of early Leydig cell steroidogenesis.

PubMed

Anbalagan, M; Yashwanth, R; Jagannadha Rao, A

2004-04-30

Postnatal Leydig cell development in rat involves an initial phase of proliferation of progenitor Leydig cells (PLCs) and subsequent differentiation of these cells into immature Leydig cells (ILCs) and adult Leydig cells (ALCs). With an objective to identify the molecular changes associated with Leydig cell differentiation, the mRNA population in PLCs and ILCs were analyzed by the technique of differential display reverse transcription polymerase chain reaction (DD-RT-PCR). Results revealed differential expression of several transcripts in PLCs and ILCs. Of the several differentially expressed transcripts, the expression of transcripts corresponding to collagen IV alpha6 (Col IV alpha6) and ribosomal protein L 41 (RpL41) decreased during the differentiation of PLC to ILC. Also there was an increase in the expression of transcripts encoding enzymes such as microsomal glutathione-S-transferase (mGST 1) and 7-dehydrocholesterol reductase (7-DHCR) during this process. While Col IV alpha6 and RpL41 are known to be involved in cellular proliferation, mGST 1 and 7-DHCR are essential for normal Leydig cell steroidogenesis. A detailed study on 7-DHCR expression in Leydig cells revealed that this enzyme plays a crucial role in steroidogenesis. Interestingly expression of this enzyme is not under acute regulation by Luteinizing hormone (LH). Copyright 2004 Elsevier Ireland Ltd.

In vitro differentiation of embryonic stem cells into hepatocytes induced by fibroblast growth factors and bone morphological protein-4.

PubMed

Zhou, Qing-Jun; Huang, Yan-Dan; Xiang, Li-Xin; Shao, Jian-Zhong; Zhou, Guo-Shun; Yao, Hang; Dai, Li-Cheng; Lu, Yong-Liang

2007-01-01

The feasibility of transforming embryonic endoderm into different cell types is tightly controlled by mesodermal and septum transversumal signalings during early embryonic development. Here, an induction protocol tracing embryonic liver development was designed, in which, three growth factors, acid fibroblast growth factor, basic fibroblast growth factor and bone morphological protein-4 that secreted from pre-cardiac mesoderm and septum transversum mesenchyme, respectively, were employed to investigate their specific potency of modulating the mature hepatocyte proportion during the differentiation process. Results showed that hepatic differentiation took place spontaneously at a low level, however, supplements of the three growth factors gave rise to a significant up-regulation of mature hepatocytes. Bone morphological protein-4 highlighted the differentiation ratio to 40-55%, showing the most effective promotion, and also exhibited a synergistic effect with the other two fibroblast factors, whereas no similar phenomenon was observed between the other two factors, which was reported for the first time. Our study not only provides a high-performance system of embryonic stem cells differentiating into hepatocytes, which would supply a sufficient hepatic population for related studies, but also make it clear of the inductive effects of three important growth factors, which could support for further investigation on the mechanisms of mesodermal and septumal derived signalings that regulate hepatic 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.

Non-linear patterns in age-related DNA methylation may reflect CD4+ T cell differentiation

PubMed Central

Johnson, Nicholas D.; Wiener, Howard W.; Smith, Alicia K.; Nishitani, Shota; Absher, Devin M.; Arnett, Donna K.; Aslibekyan, Stella; Conneely, Karen N.

2017-01-01

ABSTRACT DNA methylation (DNAm) is an important epigenetic process involved in the regulation of gene expression. While many studies have identified thousands of loci associated with age, few have differentiated between linear and non-linear DNAm trends with age. Non-linear trends could indicate early- or late-life gene regulatory processes. Using data from the Illumina 450K array on 336 human peripheral blood samples, we identified 21 CpG sites that associated with age (P<1.03E-7) and exhibited changing rates of DNAm change with age (P<1.94E-6). For 2 of these CpG sites (cg07955995 and cg22285878), DNAm increased with age at an increasing rate, indicating that differential DNAm was greatest among elderly individuals. We observed significant replication for both CpG sites (P<5.0E-8) in a second set of peripheral blood samples. In 8 of 9 additional data sets comprising samples of monocytes, T cell subtypes, and brain tissue, we observed a pattern directionally consistent with DNAm increasing with age at an increasing rate, which was nominally significant in the 3 largest data sets (4.3E-15

βIII-Gal is involved in galactan reduction during phloem element differentiation in chickpea stems.

PubMed

Martín, Ignacio; Hernández-Nistal, Josefina; Albornos, Lucía; Labrador, Emilia; Dopico, Berta

2013-06-01

βIII-Gal, a member of the chickpea β-galactosidase family, is the enzyme responsible for the cell wall autolytic process. This enzyme, whose activity increases during epicotyl growth, displays significant hydrolytic activity against cell wall pectins, and its natural substrate has been determined as an arabinogalactan from the pectic fraction of the cell wall. In the present work, the localization of βIII-Gal in different seedling and plant organs was analyzed by using specific anti-βIII-Gal antibodies. Our results revealed that besides its possible role in cell wall loosening and in early events during primary xylem and phloem fiber differentiation βIII-Gal acts on the development of sieve elements. Localization of the enzyme in this tissue, both in epicotyls and radicles from seedlings and in the different stem internodes, is consistent with the reduction in galactan during the maturation of phloem elements, as can be observed with LM5 antibodies. Thus, βIII-Gal could act on its natural substrate, the neutral side chains of rhamnogalacturonan I, contributing to cell wall reinforcement allowing phloem elements to differentiate, and conferring the necessary strengthening of the cell wall to fulfill its function. This work completes the immunolocation studies of all known chickpea β-galactosidases. Taken together, our results reflect the broad range of developmental processes covered by different members of this protein family, and confirm their crucial role in cell wall remodeling during tissue differentiation.

Divergent Macroparasite Infections in Parapatric Swiss Lake-Stream Pairs of Threespine Stickleback (Gasterosteus aculeatus)

PubMed Central

Karvonen, Anssi; Lucek, Kay; Marques, David A.; Seehausen, Ole

2015-01-01

Spatial heterogeneity in diversity and intensity of parasitism is a typical feature of most host-parasite interactions, but understanding of the evolutionary implications of such variation is limited. One possible outcome of infection heterogeneities is parasite-mediated divergent selection between host populations, ecotypes or species which may facilitate the process of ecological speciation. However, very few studies have described infections in population-pairs along the speciation continuum from low to moderate or high degree of genetic differentiation that would address the possibility of parasite-mediated divergent selection in the early stages of the speciation process. Here we provide an example of divergent parasitism in freshwater fish ecotypes by examining macroparasite infections in threespine stickleback (Gasterosteus aculeatus) of four Swiss lake systems each harbouring parapatric lake-stream ecotype pairs. We demonstrate significant differences in infections within and between the pairs that are driven particularly by the parasite taxa transmitted to fish from benthic invertebrates. The magnitude of the differences tended to correlate positively with the extent of neutral genetic differentiation between the parapatric lake and stream populations of stickleback, whereas no such correlation was found among allopatric populations from similar or contrasting habitats. This suggests that genetic differentiation is unrelated to the magnitude of parasite infection contrasts when gene flow is constrained by geographical barriers while in the absence of physical barriers, genetic differentiation and the magnitude of differences in infections tend to be positively correlated. PMID:26086778

Divergent Macroparasite Infections in Parapatric Swiss Lake-Stream Pairs of Threespine Stickleback (Gasterosteus aculeatus).

PubMed

Karvonen, Anssi; Lucek, Kay; Marques, David A; Seehausen, Ole

2015-01-01

Spatial heterogeneity in diversity and intensity of parasitism is a typical feature of most host-parasite interactions, but understanding of the evolutionary implications of such variation is limited. One possible outcome of infection heterogeneities is parasite-mediated divergent selection between host populations, ecotypes or species which may facilitate the process of ecological speciation. However, very few studies have described infections in population-pairs along the speciation continuum from low to moderate or high degree of genetic differentiation that would address the possibility of parasite-mediated divergent selection in the early stages of the speciation process. Here we provide an example of divergent parasitism in freshwater fish ecotypes by examining macroparasite infections in threespine stickleback (Gasterosteus aculeatus) of four Swiss lake systems each harbouring parapatric lake-stream ecotype pairs. We demonstrate significant differences in infections within and between the pairs that are driven particularly by the parasite taxa transmitted to fish from benthic invertebrates. The magnitude of the differences tended to correlate positively with the extent of neutral genetic differentiation between the parapatric lake and stream populations of stickleback, whereas no such correlation was found among allopatric populations from similar or contrasting habitats. This suggests that genetic differentiation is unrelated to the magnitude of parasite infection contrasts when gene flow is constrained by geographical barriers while in the absence of physical barriers, genetic differentiation and the magnitude of differences in infections tend to be positively correlated.

FGF signaling via MAPK is required early and improves Activin A-induced definitive endoderm formation from human embryonic stem cells

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

Sui, Lina, E-mail: linasui@vub.ac.be; Mfopou, Josue K.; Geens, Mieke

2012-09-28

Highlights: Black-Right-Pointing-Pointer Deep study the FGF signaling role during DE specification in the context of hESCs. Black-Right-Pointing-Pointer DE differentiation from hESCs has an early dependence on FGF signaling. Black-Right-Pointing-Pointer A serum-free DE protocol is developed based on the findings. Black-Right-Pointing-Pointer The DE cells showed potential to differentiate into pancreatic progenitor cells. -- Abstract: Considering their unlimited proliferation and pluripotency properties, human embryonic stem cells (hESCs) constitute a promising resource applicable for cell replacement therapy. To facilitate this clinical translation, it is critical to study and understand the early stage of hESCs differentiation wherein germ layers are defined. In this study,more » we examined the role of FGF signaling in Activin A-induced definitive endoderm (DE) differentiation in the absence of supplemented animal serum. We found that activated FGF/MAPK signaling is required at the early time point of Activin A-induced DE formation. In addition, FGF activation increased the number of DE cells compared to Activin A alone. These DE cells could further differentiate into PDX1 and NKX6.1 positive pancreatic progenitors in vitro. We conclude that Activin A combined with FGF/MAPK signaling efficiently induce DE cells in the absence of serum. These findings improve our understanding of human endoderm formation, and constitute a step forward in the generation of clinical grade hESCs progenies for cell therapy.« less

Clinical implications in laboratory parameter values in acute Kawasaki disease for early diagnosis and proper treatment.

PubMed

Seo, Yu-Mi; Kang, Hyun-Mi; Lee, Sung-Churl; Yu, Jae-Won; Kil, Hong-Ryang; Rhim, Jung-Woo; Han, Ji-Whan; Lee, Kyung-Yil

2018-05-01

This study aimed to analyse laboratory values according to fever duration, and evaluate the relationship across these values during the acute phase of Kawasaki disease (KD) to aid in the early diagnosis for early-presenting KD and incomplete KD patients. Clinical and laboratory data of patients with KD (n=615) were evaluated according to duration of fever at presentation, and were compared between patients with and without coronary artery lesions (CALs). For evaluation of the relationships across laboratory indices, patients with a fever duration of 5 days or 6 days were used (n=204). The mean fever duration was 6.6±2.3 days, and the proportions of patients with CALs was 19.3% (n=114). C-reactive proteins (CRPs) and neutrophil differential values were highest and hemoglobin, albumin, and lymphocyte differential values were lowest in the 6-day group. Patients with CALs had longer total fever duration, higher CRP and neutrophil differential values and lower hemoglobin and albumin values compared to patients without CALs. CRP, albumin, neutrophil differential, and hemoglobin values at the peak inflammation stage of KD showed positive or negative correlations each other. The severity of systemic inflammation in KD was reflected in the laboratory values including CRP, neutrophil differential, albumin, and hemoglobin. Observing changes in these laboratory parameters by repeated examinations prior to the peak of inflammation in acute KD may aid in diagnosis of early-presenting KD patients.

Analysis of cell cycle-related proteins in gastric intramucosal differentiated-type cancers based on mucin phenotypes: a novel hypothesis of early gastric carcinogenesis based on mucin phenotype

PubMed Central

2010-01-01

Background Abnormalities of cell cycle regulators are common features in human cancers, and several of these factors are associated with the early development of gastric cancers. However, recent studies have shown that gastric cancer tumorigenesis was characterized by mucin expression. Thus, expression patterns of cell cycle-related proteins were investigated in the early phase of differentiated-type gastric cancers to ascertain any mechanistic relationships with mucin phenotypes. Methods Immunostaining for Cyclins D1, A, E, and p21, p27, p53 and β-catenin was used to examine impairments of the cell cycle in 190 gastric intramucosal differentiated-type cancers. Mucin phenotypes were determined by the expressions of MUC5AC, MUC6, MUC2 and CD10. A Ki-67 positive rate (PR) was also examined. Results Overexpressions of p53, cyclin D1 and cyclin A were significantly more frequent in a gastric phenotype than an intestinal phenotype. Cyclin A was overexpressed in a mixed phenotype compared with an intestinal phenotype, while p27 overexpression was more frequent in an intestinal phenotype than in a mixed phenotype. Reduction of p21 was a common feature of the gastric intramucosal differentiated-type cancers examined. Conclusions Our results suggest that the levels of some cell cycle regulators appear to be associated with mucin phenotypes of early gastric differentiated-type cancers. PMID:20525401

Identification of Secretory Odontoblasts Using DMP1-GFP Transgenic Mice

PubMed Central

Balic, Anamaria; Mina, Mina

2011-01-01

Terminal differentiation of odontoblasts from dental papilla is a long process involving several intermediate steps and changes in the transcriptional profile and expression of proteins secreted by cells in the odontoblast lineage. Transgenic mouse lines in which GFP expression is under the control of tissue-and stage specific promoters have provided powerful experimental tools for identification and isolation of cells at specific stages of differentiation along a lineage. Our previous studies showed utilization of pOBCol3.6GFP and pOBCol2.3GFP animals for identification of odontoblasts at early and late stages of polarization respectively. In the present study we used the DMP1-GFP transgenic animal as an experimental model to examine its expression during the differentiation of odontoblasts from progenitor cells in vivo and in vitro. Our observations showed that DMP1-GFP transgene is first activated in secretory/functional odontoblasts engaged in secretion of predentin and then transiently expressed at high levels in newly differentiated odontoblasts. Expression of DMP1-GFP was down-regulated in highly differentiated odontoblasts. The temporal and spatial pattern of expression of DMP1-GFP transgene closely mimics the expression of endogenous DMP1. This transgenic animal will facilitate studies of gene expression and biological functions in secretory/functional odontoblasts. PMID:21172466

Hadean silicate differentiation preserved by anomalous 142Nd/144Nd ratios in the Réunion hotspot source

NASA Astrophysics Data System (ADS)

Peters, Bradley J.; Carlson, Richard W.; Day, James M. D.; Horan, Mary F.

2018-03-01

Active volcanic hotspots can tap into domains in Earth’s deep interior that were formed more than two billion years ago. High-precision data on variability in tungsten isotopes have shown that some of these domains resulted from differentiation events that occurred within the first fifty million years of Earth history. However, it has not proved easy to resolve analogous variability in neodymium isotope compositions that would track regions of Earth’s interior whose composition was established by events occurring within roughly the first five hundred million years of Earth history. Here we report 142Nd/144Nd ratios for Réunion Island igneous rocks, some of which are resolvably either higher or lower than the ratios in modern upper-mantle domains. We also find that Réunion 142Nd/144Nd ratios correlate with helium-isotope ratios (3He/4He), suggesting parallel behaviour of these isotopic systems during very early silicate differentiation, perhaps as early as 4.39 billion years ago. The range of 142Nd/144Nd ratios in Réunion basalts is inconsistent with a single-stage differentiation process, and instead requires mixing of a conjugate melt and residue formed in at least one melting event during the Hadean eon, 4.56 billion to 4 billion years ago. Efficient post-Hadean mixing nearly erased the ancient, anomalous 142Nd/144Nd signatures, and produced the relatively homogeneous 143Nd/144Nd composition that is characteristic of Réunion basalts. Our results show that Réunion magmas tap into a particularly ancient, primitive source compared with other volcanic hotspots, offering insight into the formation and preservation of ancient heterogeneities in Earth’s interior.

The zebrafish gene cloche acts upstream of a flk-1 homologue to regulate endothelial cell differentiation.

PubMed

Liao, W; Bisgrove, B W; Sawyer, H; Hug, B; Bell, B; Peters, K; Grunwald, D J; Stainier, D Y

1997-01-01

The zebrafish cloche mutation affects both the endothelial and hematopoietic lineages at a very early stage (Stainier, D. Y. R., Weinstein, B. M., Detrich, H. W., Zon, L. I. and Fishman, M. C. (1995). Development 121, 3141-3150). The most striking vascular phenotype is the absence of endocardial cells from the heart. Microscopic examination of mutant embryos reveals the presence of endothelial-like cells in the lower trunk and tail regions while head vessels appear to be missing, indicating a molecular diversification of the endothelial lineage. Cell transplantation experiments show that cloche acts cell-autonomously within the endothelial lineage. To analyze further the role of cloche in regulating endothelial cell differentiation, we have examined the expression of flk-1 and tie, two receptor tyrosine kinase genes expressed early and sequentially in the endothelial lineage. In wild-type fish, flk-1-positive cells are found throughout the embryo and differentiate to form the nascent vasculature. In cloche mutants, flk-1-positive cells are found only in the lower trunk and tail regions, and this expression is delayed as compared to wild-type. Unlike the flk-1-positive cells in wild-type embryos, those in cloche mutants do not go on to express tie, suggesting that their differentiation is halted at an early stage. We also find that the cloche mutation is not linked to flk-1. These data indicate that cloche affects the differentiation of all endothelial cells and that it acts at a very early stage, either by directly regulating flk-1 expression or by controlling the differentiation of cells that normally develop to express flk-1. cloche mutants also have a blood deficit and their hematopoietic tissues show no expression of the hematopoietic transcription factor genes GATA-1 or GATA-2 at early stages. Because the appearance of distinct levels of flk-1 expression is delayed in cloche mutants, we examined GATA-1 expression at late embryonic stages and found some blood cell differentiation that appears to be limited to the region lined by the flk-1-expressing cells. The spatial restriction of blood in the ventroposterior-most region of cloche mutant embryos may be indicative of a ventral source of signal(s) controlling hematopoietic differentiation. In addition, the restricted colocalization of blood and endothelium in cloche mutants suggests that important interactions occur between these two lineages during normal development.

The expression analysis of Sfrs10 and Celf4 during mouse retinal development

PubMed Central

Karunakaran, Devi Krishna Priya; Congdon, Sean; Guerrette, Thomas; Banday, Abdul Rouf; Lemoine, Christopher; Chhaya, Nisarg; Kanadia, Rahul

2013-01-01

Processing of mRNAs including, alternative splicing (AS), mRNA transport and translation regulation are crucial to eukaryotic gene expression. For example, >90% of the gene in the human genome are known to undergo alternative splicing thereby expanding the proteome production capacity of a limited number of genes. Similarly, mRNA export and translation regulation plays a vital role in regulating protein production. Thus, it is important to understand how these RNA binding proteins including alternative splicing factors (ASFs) and mRNA transport and translation factors regulate these processes. Here we report the expression of an ASF, Serine-arginine rich splicing factor 10 (Sfrs10) and a mRNA translation regulation factor, CUGBP, elav like family member 4 (Celf4) in the developing mouse retina. Sfrs10 was expressed throughout postnatal (P) retinal development and was observed progressively in newly differentiating neurons. Immunofluorescence (IF) showed Sfrs10 in retinal ganglion cells (RGCs) at P0, followed by amacrine and bipolar cells, and at P8 it was enriched in red/green cone photoreceptor cells. By P22, Sfrs10 was observed in rod photoreceptors in a peri-nuclear pattern. Like Sfrs10, Celf4 was also observed in the developing retina, but with two distinct retinal isoforms. In situ hybridization (ISH) showed progressive expression of Celf4 in differentiating neurons, which was confirmed by IF that showed a dynamic shift in Celf4 localization. Early in development Celf4 expression was restricted to the nuclei of newly differentiating RGCs and later (E16 onwards) it was observed in the initial segments of RGC axons. Later, during postnatal development, Celf4 was observed in amacrine and bipolar cells, but here it was predominantly cytoplasmic and enriched in the two synaptic layers. Specifically, at P14, Celf4 was observed in the synaptic boutons of rod bipolar cells marked by Pkc-α. Thus, Celf4 might be regulating AS early in development besides its known role of regulating mRNA localization/translation. In all, our data suggests an important role for AS and mRNA localization/translation in retinal neuron differentiation. PMID:23932931

Neural processing of race by individuals with Williams syndrome: Do they show the other-race effect? (And why it matters)

PubMed Central

Fishman, Inna; Ng, Rowena; Bellugi, Ursula

2012-01-01

Williams syndrome (WS) is a genetic condition with a distinctive social phenotype characterized by excessive sociability, accompanied by a relative proficiency in face recognition, despite severe deficits in visuospatial domain of cognition. This consistent phenotypic characteristic and the relative homogeneity of the WS genotype make WS a compelling human model for examining the genotype-phenotype relations, especially with respect to social behavior. Following up on a recent report suggesting that individuals with WS do not show race bias and racial stereotyping, this study was designed to investigate the neural correlates of the perception of faces from different races, in individuals with WS as compared to typically developing (TD) controls. Caucasian WS and TD participants performed a gender identification task with own-race (White) and other-race (Black) faces while event-related potentials (ERPs) were recorded. In line with previous studies with TD participants, other-race faces elicited larger amplitudes ERPs within the first 200 ms following the face onset, in WS and TD participants alike. These results suggest that, just like their TD counterparts, individuals with WS differentially processed faces of own- vs. other-race, at relatively early stages of processing, starting as early as 115 ms after the face onset. Overall, these results indicate that neural processing of faces in individuals with WS is moderated by race at early perceptual stages, calling for a reconsideration of the previous claim that they are uniquely insensitive to race. PMID:22022973

Proteomic analysis by iTRAQ in red claw crayfish, Cherax quadricarinatus, hematopoietic tissue cells post white spot syndrome virus infection.

PubMed

Jeswin, Joseph; Xie, Xiao-lu; Ji, Qiao-lin; Wang, Ke-jian; Liu, Hai-peng

2016-03-01

To elucidate proteomic changes of Hpt cells from red claw crayfish, Cherax quadricarinatus, we have carried out isobaric tags for relative and absolute quantitation (iTRAQ) of cellular proteins at both early (1 hpi) and late stage (12 hpi) post white spot syndrome virus (WSSV) infection. Protein database search revealed 594 protein hits by Mascot, in which 17 and 30 proteins were present as differentially expressed proteins at early and late viral infection, respectively. Generally, these differentially expressed proteins include: 1) the metabolic process related proteins in glycolysis and glucogenesis, DNA replication, nucleotide/amino acid/fatty acid metabolism and protein biosynthesis; 2) the signal transduction related proteins like small GTPases, G-protein-alpha stimulatory subunit, proteins bearing PDZ- or 14-3-3-domains that help holding together and organize signaling complexes, casein kinase I and proteins of the MAP-kinase signal transduction pathway; 3) the immune defense related proteins such as α-2 macroglobulin, transglutaminase and trans-activation response RNA-binding protein 1. Taken together, these protein information shed new light on the host cellular response against WSSV infection in a crustacean cell culture. Copyright © 2016 Elsevier Ltd. All rights reserved.

Decidualization and angiogenesis in early pregnancy: unravelling the functions of DC and NK cells.

PubMed

Blois, Sandra M; Klapp, Burghard F; Barrientos, Gabriela

2011-03-01

Differentiation of endometrial stromal cells and formation of new maternal blood vessels at the time of embryo implantation are critical for the establishment and maintenance of gestation. The regulatory functions of decidual leukocytes during early pregnancy, particularly dendritic cells (DC) and NK cells, may be important not only for the generation of maternal immunological tolerance but also in the regulation of stromal cell differentiation and the vascular responses associated with the implantation process. However, the specific contributions of DC and NK cells during implantation are still difficult to dissect mainly due to reciprocal regulatory interactions established between them within the decidualizing microenvironment. The present review article discusses current evidence on the regulatory pathways driving decidualization in mice, suggesting that NK cells promote uterine vascular modifications that assist decidual growth but DC directly control stromal cell proliferation, angiogenesis and the homing and maturation of NK cell precursors in the pregnant uterus. Thus, successful implantation appears to result from an interplay between cellular components of the decidualizing endometrium involving immunoregulatory and pro-angiogenic functions of DC and NK cells. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Preliminary results from the COBE differential microwave radiometers - Large angular scale isotropy of the cosmic microwave background

NASA Technical Reports Server (NTRS)

Smoot, G. F.; Aymon, J.; Bennett, C. L.; Kogut, A.; Backus, C.

1991-01-01

Preliminary but precise micowave maps are presented of the sky, and thus of the early universe, derived as the first results from the Differential Microwave Radiometers experiment aboard COBE. The dipole anisotropy attributed to the motion of the solar system with respect to the CMB reference frame shows strongly in all six sky maps and is consistent with a Doppler-shifted thermal spectrum. The best-fitted dipole has amplitude 3.3 + or - 0.2 mK in the direction (alpha, delta) = 11.2 h + or - 0.2 h, -7 deg + or - 2 deg (J2000) or (l,b) = 265 deg + or - 2 deg, 48 deg + or - 2 deg. There is no clear evidence in the maps for any other large angular-scale feature. Limits on Delta T/T0 of 3 x 10 to the -5th (T0 = 2.735 K), 4 x 10 to the -5th, and 4 x 10 to the -5th are found for the rms quadrupole amplitude, monochromatic fluctuations, and Gaussian fluctuations, respectively. These measurements place the most severe constraints to date on many potential physical processes in the early universe.

Dictyostelium cell death

PubMed Central

Levraud, Jean-Pierre; Adam, Myriam; Luciani, Marie-Françoise; de Chastellier, Chantal; Blanton, Richard L.; Golstein, Pierre

2003-01-01

Cell death in the stalk of Dictyostelium discoideum, a prototypic vacuolar cell death, can be studied in vitro using cells differentiating as a monolayer. To identify early events, we examined potentially dying cells at a time when the classical signs of Dictyostelium cell death, such as heavy vacuolization and membrane lesions, were not yet apparent. We observed that most cells proceeded through a stereotyped series of differentiation stages, including the emergence of “paddle” cells showing high motility and strikingly marked subcellular compartmentalization with actin segregation. Paddle cell emergence and subsequent demise with paddle-to-round cell transition may be critical to the cell death process, as they were contemporary with irreversibility assessed through time-lapse videos and clonogenicity tests. Paddle cell demise was not related to formation of the cellulose shell because cells where the cellulose-synthase gene had been inactivated underwent death indistinguishable from that of parental cells. A major subcellular alteration at the paddle-to-round cell transition was the disappearance of F-actin. The Dictyostelium vacuolar cell death pathway thus does not require cellulose synthesis and includes early actin rearrangements (F-actin segregation, then depolymerization), contemporary with irreversibility, corresponding to the emergence and demise of highly polarized paddle cells. PMID:12654899

When the future becomes the past: Differences in brain activation patterns for episodic memory and episodic future thinking.

PubMed

Weiler, Julia A; Suchan, Boris; Daum, Irene

2010-10-15

Episodic memory and episodic future thinking activate a network of overlapping brain regions, but little is known about the mechanism with which the brain separates the two processes. It was recently suggested that differential activity for memory and future thinking may be linked to differences in the phenomenal properties (e.g., richness of detail). Using functional magnetic resonance imaging in healthy subjects and a novel experimental design, we investigated the networks involved in the imagery of future and the recall of past events for the same target occasion, i.e. the Christmas and New Year's holidays, thereby keeping temporal distance and content similar across conditions. Although ratings of phenomenal characteristics were comparable for future thoughts and memories, differential activation patterns emerged. The right posterior hippocampus exhibited stronger memory-related activity during early event recall, and stronger future thought-related activity during late event imagination. Other regions, e.g., the precuneus and lateral prefrontal cortex, showed the reverse activation pattern with early future-associated and late past-associated activation. Memories compared to future thoughts were further related to stronger activation in several visual processing regions, which accords with a reactivation of the original perceptual experience. In conclusion, the results showed for the first time unique neural signatures for both memory and future thinking even in the absence of differences in phenomenal properties and suggested different time courses of brain activation for episodic memory and future thinking. Copyright 2010 Elsevier B.V. All rights reserved.

Aubergine Controls Germline Stem Cell Self-Renewal and Progeny Differentiation via Distinct Mechanisms.

PubMed

Ma, Xing; Zhu, Xiujuan; Han, Yingying; Story, Benjamin; Do, Trieu; Song, Xiaoqing; Wang, Su; Zhang, Ying; Blanchette, Marco; Gogol, Madelaine; Hall, Kate; Peak, Allison; Anoja, Perera; Xie, Ting

2017-04-24

Piwi family protein Aubergine (Aub) maintains genome integrity in late germ cells of the Drosophila ovary through Piwi-associated RNA-mediated repression of transposon activities. Although it is highly expressed in germline stem cells (GSCs) and early progeny, it remains unclear whether it plays any roles in early GSC lineage development. Here we report that Aub promotes GSC self-renewal and GSC progeny differentiation. RNA-iCLIP results show that Aub binds the mRNAs encoding self-renewal and differentiation factors in cultured GSCs. Aub controls GSC self-renewal by preventing DNA-damage-induced Chk2 activation and by translationally controlling the expression of self-renewal factors. It promotes GSC progeny differentiation by translationally controlling the expression of differentiation factors, including Bam. Therefore, this study reveals a function of Aub in GSCs and their progeny, which promotes translation of self-renewal and differentiation factors by directly binding to its target mRNAs and interacting with translational initiation factors. Copyright © 2017 Elsevier Inc. All rights reserved.

Cineromycin B isolated from Streptomyces cinerochromogenes inhibits adipocyte differentiation of 3T3-L1 cells via Krüppel-like factors 2 and 3.

PubMed

Matsuo, Hirotaka; Kondo, Yoshiyuki; Kawasaki, Takashi; Imamura, Nobutaka

2015-08-15

3T3-L1 cells are preadipocytes and often used as a model for cellular differentiation to adipocytes; however, the mechanism of this differentiation is not completely understood even in these model cells. In this study, we sought to identify a unique anti-adipogenesis agent from microorganisms and to examine its mechanism of action to gain knowledge and create a tool and/or seed compound for anti-obesity drug discovery research. Screening for anti-adipogenesis agents from microorganisms was performed using a 3T3-L1 cell differentiation system, and an active compound was isolated. The inhibitory mechanism of the compound was investigated by measuring the expression of key regulators using quantitative real-time PCR and Western blot analysis. The compound with anti-adipogenic activity in 3T3-L1 cells was identified as cineromycin B. Cineromycin B at 50 μg/mL suppressed intracellular lipid accumulation and the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha (C/EBPα), which are master regulators of adipocyte differentiation. Further investigations showed that cineromycin B increased significantly the mRNA expression of two negative regulators of adipocyte differentiation, Krüppel-like factor (KLF) 2 and KLF3, at an early stage of the differentiation. The results of siRNA transfection experiments indicated that cineromycin B is a unique adipocyte differentiation inhibitor, acting mainly via upregulation of KLF2 and KLF3, and these KLFs may play a role in the early stage of differentiation. Cineromycin B inhibited adipocyte differentiation in 3T3-L1 cells mainly via upregulation of KLF2 and KLF3 mRNA expression at an early stage of the differentiation. Copyright © 2015. Published by Elsevier Inc.

Reactive Oxygen Species in Planarian Regeneration: An Upstream Necessity for Correct Patterning and Brain Formation

PubMed Central

Pirotte, Nicky; Stevens, An-Sofie; Fraguas, Susanna; Plusquin, Michelle; Van Roten, Andromeda; Van Belleghem, Frank; Paesen, Rik; Ameloot, Marcel; Cebrià, Francesc; Artois, Tom; Smeets, Karen

2015-01-01

Recent research highlighted the impact of ROS as upstream regulators of tissue regeneration. We investigated their role and targeted processes during the regeneration of different body structures using the planarian Schmidtea mediterranea, an organism capable of regenerating its entire body, including its brain. The amputation of head and tail compartments induces a ROS burst at the wound site independently of the orientation. Inhibition of ROS production by diphenyleneiodonium (DPI) or apocynin (APO) causes regeneration defaults at both the anterior and posterior wound sites, resulting in reduced regeneration sites (blastemas) and improper tissue homeostasis. ROS signaling is necessary for early differentiation and inhibition of the ROS burst results in defects on the regeneration of the nervous system and on the patterning process. Stem cell proliferation was not affected, as indicated by histone H3-P immunostaining, fluorescence-activated cell sorting (FACS), in situ hybridization of smedwi-1, and transcript levels of proliferation-related genes. We showed for the first time that ROS modulate both anterior and posterior regeneration in a context where regeneration is not limited to certain body structures. Our results indicate that ROS are key players in neuroregeneration through interference with the differentiation and patterning processes. PMID:26180588

Mediator Med23 deficiency enhances neural differentiation of murine embryonic stem cells through modulating BMP signaling.

PubMed

Zhu, Wanqu; Yao, Xiao; Liang, Yan; Liang, Dan; Song, Lu; Jing, Naihe; Li, Jinsong; Wang, Gang

2015-02-01

Unraveling the mechanisms underlying early neural differentiation of embryonic stem cells (ESCs) is crucial to developing cell-based therapies of neurodegenerative diseases. Neural fate acquisition is proposed to be controlled by a 'default' mechanism, for which the molecular regulation is not well understood. In this study, we investigated the functional roles of Mediator Med23 in pluripotency and lineage commitment of murine ESCs. Unexpectedly, we found that, despite the largely unchanged pluripotency and self-renewal of ESCs, Med23 depletion rendered the cells prone to neural differentiation in different differentiation assays. Knockdown of two other Mediator subunits, Med1 and Med15, did not alter the neural differentiation of ESCs. Med15 knockdown selectively inhibited endoderm differentiation, suggesting the specificity of cell fate control by distinctive Mediator subunits. Gene profiling revealed that Med23 depletion attenuated BMP signaling in ESCs. Mechanistically, MED23 modulated Bmp4 expression by controlling the activity of ETS1, which is involved in Bmp4 promoter-enhancer communication. Interestingly, med23 knockdown in zebrafish embryos also enhanced neural development at early embryogenesis, which could be reversed by co-injection of bmp4 mRNA. Taken together, our study reveals an intrinsic, restrictive role of MED23 in early neural development, thus providing new molecular insights for neural fate determination. © 2015. Published by The Company of Biologists Ltd.

gone early, a Novel Germline Factor, Ensures the Proper Size of the Stem Cell Precursor Pool in the Drosophila Ovary

PubMed Central

Matsuoka, Shinya; Gupta, Swati; Suzuki, Emiko; Hiromi, Yasushi; Asaoka, Miho

2014-01-01

In order to sustain lifelong production of gametes, many animals have evolved a stem cell–based gametogenic program. In the Drosophila ovary, germline stem cells (GSCs) arise from a pool of primordial germ cells (PGCs) that remain undifferentiated even after gametogenesis has initiated. The decision of PGCs to differentiate or remain undifferentiated is regulated by somatic stromal cells: specifically, epidermal growth factor receptor (EGFR) signaling activated in the stromal cells determines the fraction of germ cells that remain undifferentiated by shaping a Decapentaplegic (Dpp) gradient that represses PGC differentiation. However, little is known about the contribution of germ cells to this process. Here we show that a novel germline factor, Gone early (Goe), limits the fraction of PGCs that initiate gametogenesis. goe encodes a non-peptidase homologue of the Neprilysin family metalloendopeptidases. At the onset of gametogenesis, Goe was localized on the germ cell membrane in the ovary, suggesting that it functions in a peptidase-independent manner in cell–cell communication at the cell surface. Overexpression of Goe in the germline decreased the number of PGCs that enter the gametogenic pathway, thereby increasing the proportion of undifferentiated PGCs. Inversely, depletion of Goe increased the number of PGCs initiating differentiation. Excess PGC differentiation in the goe mutant was augmented by halving the dose of argos, a somatically expressed inhibitor of EGFR signaling. This increase in PGC differentiation resulted in a massive decrease in the number of undifferentiated PGCs, and ultimately led to insufficient formation of GSCs. Thus, acting cooperatively with a somatic regulator of EGFR signaling, the germline factor goe plays a critical role in securing the proper size of the GSC precursor pool. Because goe can suppress EGFR signaling activity and is expressed in EGF-producing cells in various tissues, goe may function by attenuating EGFR signaling, and thereby affecting the stromal environment. PMID:25420147

Androgens inhibit adipogenesis during human adipose stem cell commitment to predipocyte formation

PubMed Central

Chazenbalk, Gregorio; Singh, Prapti; Irge, Dana; Shah, Amy; Abbott, David H; Dumesic, Daniel A

2013-01-01

Androgens play a pivotal role in the regulation of body fat distribution. Adipogenesis is a process whereby multipotent adipose stem cells (ASCs) initially become preadipocytes (ASC commitment to preadipocytes) before differentiating into adipocytes. Androgens inhibit human (h) subcutaneous (SC) abdominal preadipocyte differentiation in both sexes, but their effects on hASC commitment to preadipocyte formation is unknown. We therefore examined whether androgen exposure to human (h) ASCs, isolated from SC abdominal adipose of nonobese women, impairs their commitment to preadipocyte formation and/or subsequent differentiation into adipocytes. For this, isolated hASCs from SC abdominal lipoaspirate were cultured in adipogenesis-inducing medium for 0.5–14 days in the presence of testosterone (T, 0–100 nM) or dihydrotestosterone (DHT, 0–50 nM). Adipogenesis was determined by immunofluorescence microscopy and by quantification of adipogenically relevant transcriptional factors, PPARγ, C/EBPα and C/EBPβ. We found that a 3-day exposure of hASCs to T (50 nM) or DHT (5 nM) in adipogenesis-inducing medium impaired lipid acquisition and decreased PPARγ, C/EBPα and C/EBPβ gene expression. The inhibitory effects of T and DHT at this early-stage of adipocyte differentiation, were partially and completely reversed by flutamide (F, 100 nM), respectively. The effect of androgens on hASC commitment to a preadipocyte phenotype was examined via activation of BMP4 signaling. T (50 nM) and DHT (5nM) significantly inhibited the stimulatory effect of BMP4-induced ASC commitment to the preadipocyte phenotype, as regards PPARγ and C/EBPα gene expression. Our findings indicate that androgens, in part through androgen receptor action, impair BMP4-induced commitment of SC hASCs to preadipocytes and also reduce early-stage adipocyte differentiation, perhaps limiting adipocyte numbers and fat storage in SC abdominal adipose. PMID:23707571

Nitric oxide releasing hydrogel promotes endothelial differentiation of mouse embryonic stem cells.

PubMed

Nie, Yan; Zhang, Kaiyue; Zhang, Shuaiqiang; Wang, Dan; Han, Zhibo; Che, Yongzhe; Kong, Deling; Zhao, Qiang; Han, Zhongchao; He, Zuo-Xiang; Liu, Na; Ma, Fengxia; Li, Zongjin

2017-11-01

Transplantation of endothelial cells (ECs) holds great promise for treating various kinds of ischemic diseases. However, the major challenge in ECs-based therapy in clinical applications is to provide high quality and enough amounts of cells. In this study, we developed a simple and efficient system to direct endothelial differentiation of mouse embryonic stem cells (ESCs) using a controllable chitosan nitric oxide (NO)-releasing hydrogel (CS-NO). ESCs were plated onto the hydrogel culture system, and the expressions of differentiation markers were measured. We found that the expression of Flk-1 (early ECs marker) and VE-cadherin (mature ECs marker) increased obviously under the controlled NO releasing environment. Moreover, the Flk-1 upregulation was accompanied by the activation of the phospho-inositide-3 kinase (PI3K)/Akt signaling. We also found that in the presence of the PI3K inhibitor (LY294002), the endothelial commitment of ESCs was abolished, indicating the importance of Akt phosphorylation in the endothelial differentiation of ESCs. Interestingly, in the absence of NO, the activation of Akt phosphorylation alone by using AKT activator (SC-79) did not profoundly promote the endothelial differentiation of ESCs, suggesting an interdependent relationship between NO and the Akt phosphorylation in driving endothelial fate specification of ESCs. Taken together, we demonstrated that NO releasing in a continuous and controlled manner is a simple and efficient method for directing the endothelial differentiation of ESCs without adding growth factors. Fascinating data continues to show that artificial stem cell niche not only serve as a physical supporting scaffold for stem cells proliferation, but also as a novel platform for directing stem cell differentiation. Because of the lack of proper microenvironment for generating therapeutic endothelial cells (ECs) in vitro, the source of ECs for transplantation is the major limitation in ECs-based therapy to clinical applications. The current study established a feeder cell-free, 2-dimensional culture system for promoting the differentiation processes of embryonic stem cells (ESCs) committed to the endothelial lineage via using a nitric oxide (NO) controlled releasing hydrogel (CS-NO). Notably, the NO releasing from the hydrogel could selectively up-regulate Flk-1 (early ECs marker) and VE-cadherin (mature ECs marker) in the absence of growth factors, which was of crucial importance in the endothelial differentiation of ESCs. In summary, the current study proposes a simple and efficient method for directing the endothelial differentiation of ESCs without extra growth factors. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Is it growing exponentially fast? -- Impact of assuming exponential growth for characterizing and forecasting epidemics with initial near-exponential growth dynamics.

PubMed

Chowell, Gerardo; Viboud, Cécile

2016-10-01

The increasing use of mathematical models for epidemic forecasting has highlighted the importance of designing models that capture the baseline transmission characteristics in order to generate reliable epidemic forecasts. Improved models for epidemic forecasting could be achieved by identifying signature features of epidemic growth, which could inform the design of models of disease spread and reveal important characteristics of the transmission process. In particular, it is often taken for granted that the early growth phase of different growth processes in nature follow early exponential growth dynamics. In the context of infectious disease spread, this assumption is often convenient to describe a transmission process with mass action kinetics using differential equations and generate analytic expressions and estimates of the reproduction number. In this article, we carry out a simulation study to illustrate the impact of incorrectly assuming an exponential-growth model to characterize the early phase (e.g., 3-5 disease generation intervals) of an infectious disease outbreak that follows near-exponential growth dynamics. Specifically, we assess the impact on: 1) goodness of fit, 2) bias on the growth parameter, and 3) the impact on short-term epidemic forecasts. Designing transmission models and statistical approaches that more flexibly capture the profile of epidemic growth could lead to enhanced model fit, improved estimates of key transmission parameters, and more realistic epidemic forecasts.

Mediating human stem cell behaviour via defined fibrous architectures by melt electrospinning writing.

PubMed

Eichholz, Kian F; Hoey, David A

2018-05-29

The architecture within which cells reside is key to mediating their specific functions within the body. In this study, we use melt electrospinning writing (MEW) to fabricate cell micro-environments with various fibrous architectures to study their effect on human stem cell behaviour. We designed, built and optimised a MEW apparatus and used it to fabricate four different platform designs of 10.4±2μm fibre diameter, with angles between fibres on adjacent layers of 90°, 45°, 10° and R (random). Mechanical characterisation was conducted via tensile testing, and human skeletal stem cells (hSSCs) were seeded to scaffolds to study the effect of architecture on cell morphology and mechanosensing (nuclear YAP). Cell morphology was significantly altered between groups, with cells on 90° scaffolds having a lower aspect ratio, greater spreading, greater cytoskeletal tension and nuclear YAP expression. Long term cell culture studies were then conducted to determine the differentiation potential of scaffolds in terms of alkaline phosphatase activity, collagen and mineral production. Across these studies, an increased cell spreading in 3-dimensions is seen with decreasing alignment of architecture correlated with enhanced osteogenesis. This study therefore highlights the critical role of fibrous architecture in regulating stem cell behaviour with implications for tissue engineering and disease progression. This is the first study which has investigated the effect of controlled fibrous architectures fabricated via melt electrospinning writing on cell behaviour and differentiation. After optimising the process and characterising scaffolds via SEM and tensile testing, cells were seeded to fibrous scaffolds with various micro-architectures and studied in terms of cell morphology. Nuclear YAP expression was further investigated as a marker of cell shape, cytoskeletal tension and differentiation potential. In agreement with these early markers, long term cell culture studies revealed for the first time that a 90° fibrous architecture is optimal for the osteogenic differentiation of skeletal stem cells. This is the first study to investigate the effect of controlled fibrous material architectures fabricated via melt electrospinning writing on cell shape, mechanosignalling and differentiation. After optimising the biofabrication process and characterising scaffolds via SEM and tensile testing, cells were seeded to fibrous scaffolds with various micro-architectures and studied in terms of cell shape. Nuclear YAP expression was further investigated as a marker of cytoskeletal tension and differentiation potential. In agreement with these early markers, long term cell culture studies revealed for the first time that a 90° fibrous architecture is optimal for the osteogenic differentiation of skeletal stem cells, by driving a spread morphology and nuclear translocation of YAP in 3 dimensions . Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Characteristics of hepatic stem/progenitor cells in the fetal and adult liver.

PubMed

Koike, Hiroyuki; Taniguchi, Hideki

2012-11-01

The liver is an essential organ that maintains vital activity through its numerous important functions. It has a unique capability of fully regenerating after injury. Regulating a balance between self-renewal and differentiation of hepatic stem cells that are resources for functional mature liver cells is required for maintenance of tissue homeostasis. This review describes the characteristics of hepatic stem/progenitor cells and the regulatory mechanism of their self-renewal and differentiation capacity. In liver organogenesis, undifferentiated hepatic stem/progenitor cells expand their pool by repeated self-renewal in the early stage of liver development and then differentiate into two different types of cell lineage, namely hepatocytes and cholangiocytes. Liver development is regulated by expression of stem cell transcription factors in a complex multistep process. Recent studies suggest that stem cells are maintained by integrative regulation of gene expression patterns related to self-renewal and differentiation by epigenetic mechanisms such as histone modification and DNA methylation. Analysis of the proper regulatory mechanism of hepatic stem/progenitor cells is important for regenerative medicine that utilizes hepatic stem cells and for preventing liver cancer through clarification of the carcinogenetic mechanism involved in stem cell system failure.

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.

Comparative 2D-DIGE Proteomic Analysis of Bovine Mammary Epithelial Cells during Lactation Reveals Protein Signatures for Lactation Persistency and Milk Yield

PubMed Central

Janjanam, Jagadeesh; Singh, Surender; Jena, Manoj K.; Varshney, Nishant; Kola, Srujana; Kumar, Sudarshan; Kaushik, Jai K.; Grover, Sunita; Dang, Ajay K.; Mukesh, Manishi; Prakash, B. S.; Mohanty, Ashok K.

2014-01-01

Mammary gland is made up of a branching network of ducts that end with alveoli which surrounds the lumen. These alveolar mammary epithelial cells (MEC) reflect the milk producing ability of farm animals. In this study, we have used 2D-DIGE and mass spectrometry to identify the protein changes in MEC during immediate early, peak and late stages of lactation and also compared differentially expressed proteins in MEC isolated from milk of high and low milk producing cows. We have identified 41 differentially expressed proteins during lactation stages and 22 proteins in high and low milk yielding cows. Bioinformatics analysis showed that a majority of the differentially expressed proteins are associated in metabolic process, catalytic and binding activity. The differentially expressed proteins were mapped to the available biological pathways and networks involved in lactation. The proteins up-regulated during late stage of lactation are associated with NF-κB stress induced signaling pathways and whereas Akt, PI3K and p38/MAPK signaling pathways are associated with high milk production mediated through insulin hormone signaling. PMID:25111801

Autophagic flux is highly active in early mitosis and differentially regulated throughout the cell cycle

PubMed Central

Li, Zhiyuan; Ji, Xinmiao; Wang, Dongmei; Liu, Juanjuan; Zhang, Xin

2016-01-01

Mitosis is a fast process that involves dramatic cellular remodeling and has a high energy demand. Whether autophagy is active or inactive during the early stages of mitosis in a naturally dividing cell is still debated. Here we aimed to use multiple assays to resolve this apparent discrepancy. Although the LC3 puncta number was reduced in mitosis, the four different cell lines we tested all have active autophagic flux in both interphase and mitosis. In addition, the autophagic flux was highly active in nocodazole-induced, double-thymidine synchronization released as well as naturally occurring mitosis in HeLa cells. Multiple autophagy proteins are upregulated in mitosis and the increased Beclin-1 level likely contributes to the active autophagic flux in early mitosis. It is interesting that although the autophagic flux is active throughout the cell cycle, early mitosis and S phase have relatively higher autophagic flux than G1 and late G2 phases, which might be helpful to degrade the damaged organelles and provide energy during S phase and mitosis. PMID:27213594

Autophagic flux is highly active in early mitosis and differentially regulated throughout the cell cycle.

PubMed

Li, Zhiyuan; Ji, Xinmiao; Wang, Dongmei; Liu, Juanjuan; Zhang, Xin

2016-06-28

Mitosis is a fast process that involves dramatic cellular remodeling and has a high energy demand. Whether autophagy is active or inactive during the early stages of mitosis in a naturally dividing cell is still debated. Here we aimed to use multiple assays to resolve this apparent discrepancy. Although the LC3 puncta number was reduced in mitosis, the four different cell lines we tested all have active autophagic flux in both interphase and mitosis. In addition, the autophagic flux was highly active in nocodazole-induced, double-thymidine synchronization released as well as naturally occurring mitosis in HeLa cells. Multiple autophagy proteins are upregulated in mitosis and the increased Beclin-1 level likely contributes to the active autophagic flux in early mitosis. It is interesting that although the autophagic flux is active throughout the cell cycle, early mitosis and S phase have relatively higher autophagic flux than G1 and late G2 phases, which might be helpful to degrade the damaged organelles and provide energy during S phase and mitosis.

Impact of drought on the temporal dynamics of wood formation in Pinus sylvestris

PubMed Central

GRUBER, ANDREAS; STROBL, STEFAN; VEIT, BARBARA; OBERHUBER, WALTER

2011-01-01

Summary We determined the temporal dynamics of cambial activity and xylem cell differentiation of Scots pine (Pinus sylvestris L.) within a dry inner Alpine valley (750 m asl, Tyrol, Austria), where radial growth is strongly limited by drought in spring. Repeated micro-sampling of the developing tree ring of mature trees was carried out during 2 contrasting years at two study plots that differ in soil water availability (xeric and dry-mesic site). In 2007, when air temperature at the beginning of the growing season in April exceeded the long-term mean by 6.4 °C, cambial cell division started in early April at both study plots. A delayed onset of cambial activity of c. 2 wk was found in 2008, when average climate conditions prevailed in spring, indicating that resumption of cambial cell division after winter dormancy is temperature-controlled. Cambial cell division consistently ended about the end of June/early July in both study years. Radial enlargement of tracheids started almost 3 wk earlier in 2007 compared with 2008 at both study plots. At the xeric site, the maximum rate of tracheid production in 2007 and 2008 was reached in early and mid-May, respectively, and c. 2 wk later, at the dry-mesic site. Since in both study years, more favorable growing conditions (i.e., an increase in soil water content) were recorded during summer, we suggest a strong sink competition for carbohydrates to mycorrhizal root and shoot growth. Wood formation stopped c. 4 wk earlier at the xeric compared with the dry-mesic site in both years, indicating a strong influence of drought stress on cell differentiation. This is supported by radial widths of earlywood cells, which were found to be significantly narrower at the xeric than at the dry-mesic site (P < 0.05). Repeated cellular analyses during the two growing seasons revealed that, although spatial variability in the dynamics and duration of cell differentiation processes in Pinus sylvestris exposed to drought is strongly influenced by water availability, the onset of cambial activity and cell differentiation is controlled by temperature. PMID:20197285

Impact of drought on the temporal dynamics of wood formation in Pinus sylvestris.

PubMed

Gruber, Andreas; Strobl, Stefan; Veit, Barbara; Oberhuber, Walter

2010-04-01

We determined the temporal dynamics of cambial activity and xylem cell differentiation of Scots pine (Pinus sylvestris L.) within a dry inner Alpine valley (750 m a.s.l., Tyrol, Austria), where radial growth is strongly limited by drought in spring. Repeated micro-sampling of the developing tree ring of mature trees was carried out during two contrasting years at two study plots that differ in soil water availability (xeric and dry-mesic sites). In 2007, when air temperature at the beginning of the growing season in April exceeded the long-term mean by 6.4 degrees C, cambial cell division started in early April at both study plots. A delayed onset of cambial activity of c. 2 weeks was found in 2008, when average climate conditions prevailed in spring, indicating that resumption of cambial cell division after winter dormancy is temperature controlled. Cambial cell division consistently ended about the end of June/early July in both study years. Radial enlargement of tracheids started almost 3 weeks earlier in 2007 compared with 2008 at both study plots. At the xeric site, the maximum rate of tracheid production in 2007 and 2008 was reached in early and mid-May, respectively, and c. 2 weeks later at the dry-mesic site. Since in both study years more favorable growing conditions (i.e., an increase in soil water content) were recorded during summer, we suggest a strong sink competition for carbohydrates to mycorrhizal root and shoot growth. Wood formation stopped c. 4 weeks earlier at the xeric compared with the dry-mesic site in both years, indicating a strong influence of drought stress on cell differentiation. This is supported by radial widths of earlywood cells, which were found to be significantly narrower at the xeric than at the dry-mesic site (P < 0.05). Repeated cellular analyses during the two growing seasons revealed that, although spatial variability in the dynamics and duration of cell differentiation processes in P. sylvestris exposed to drought is strongly influenced by water availability, the onset of cambial activity and cell differentiation is controlled by temperature.

Metal-Silicate Segregation in Asteroidal Meteorites

NASA Technical Reports Server (NTRS)

Herrin, Jason S.; Mittlefehldt, D. W.

2006-01-01

A fundamental process of planetary differentiation is the segregation of metal-sulfide and silicate phases, leading eventually to the formation of a metallic core. Asteroidal meteorites provide a glimpse of this process frozen in time from the early solar system. While chondrites represent starting materials, iron meteorites provide an end product where metal has been completely concentrated in a region of the parent asteroid. A complimentary end product is seen in metal-poor achondrites that have undergone significant igneous processing, such as angrites, HED's and the majority of aubrites. Metal-rich achondrites such as acapulcoite/lodranites, winonaites, ureilites, and metal-rich aubrites may represent intermediate stages in the metal segregation process. Among these, acapulcoite-lodranites and ureilites are examples of primary metal-bearing mantle restites, and therefore provide an opportunity to observe the metal segregation process that was captured in progress. In this study we use bulk trace element compositions of acapulcoites-lodranites and ureilites for this purpose.

Automatic Semantic Facilitation in Anterior Temporal Cortex Revealed through Multimodal Neuroimaging

PubMed Central

Gramfort, Alexandre; Hämäläinen, Matti S.; Kuperberg, Gina R.

2013-01-01

A core property of human semantic processing is the rapid, facilitatory influence of prior input on extracting the meaning of what comes next, even under conditions of minimal awareness. Previous work has shown a number of neurophysiological indices of this facilitation, but the mapping between time course and localization—critical for separating automatic semantic facilitation from other mechanisms—has thus far been unclear. In the current study, we used a multimodal imaging approach to isolate early, bottom-up effects of context on semantic memory, acquiring a combination of electroencephalography (EEG), magnetoencephalography (MEG), and functional magnetic resonance imaging (fMRI) measurements in the same individuals with a masked semantic priming paradigm. Across techniques, the results provide a strikingly convergent picture of early automatic semantic facilitation. Event-related potentials demonstrated early sensitivity to semantic association between 300 and 500 ms; MEG localized the differential neural response within this time window to the left anterior temporal cortex, and fMRI localized the effect more precisely to the left anterior superior temporal gyrus, a region previously implicated in semantic associative processing. However, fMRI diverged from early EEG/MEG measures in revealing semantic enhancement effects within frontal and parietal regions, perhaps reflecting downstream attempts to consciously access the semantic features of the masked prime. Together, these results provide strong evidence that automatic associative semantic facilitation is realized as reduced activity within the left anterior superior temporal cortex between 300 and 500 ms after a word is presented, and emphasize the importance of multimodal neuroimaging approaches in distinguishing the contributions of multiple regions to semantic processing. PMID:24155321

How Human Amygdala and Bed Nucleus of the Stria Terminalis May Drive Distinct Defensive Responses.

PubMed

Klumpers, Floris; Kroes, Marijn C W; Baas, Johanna M P; Fernández, Guillén

2017-10-04

The ability to adaptively regulate responses to the proximity of potential danger is critical to survival and imbalance in this system may contribute to psychopathology. The bed nucleus of the stria terminalis (BNST) is implicated in defensive responding during uncertain threat anticipation whereas the amygdala may drive responding upon more acute danger. This functional dissociation between the BNST and amygdala is however controversial, and human evidence scarce. Here we used data from two independent functional magnetic resonance imaging studies [ n = 108 males and n = 70 (45 females)] to probe how coordination between the BNST and amygdala may regulate responses during shock anticipation and actual shock confrontation. In a subset of participants from Sample 2 ( n = 48) we demonstrate that anticipation and confrontation evoke bradycardic and tachycardic responses, respectively. Further, we show that in each sample when going from shock anticipation to the moment of shock confrontation neural activity shifted from a region anatomically consistent with the BNST toward the amygdala. Comparisons of functional connectivity during threat processing showed overlapping yet also consistently divergent functional connectivity profiles for the BNST and amygdala. Finally, childhood maltreatment levels predicted amygdala, but not BNST, hyperactivity during shock anticipation. Our results support an evolutionary conserved, defensive distance-dependent dynamic balance between BNST and amygdala activity. Shifts in this balance may enable shifts in defensive reactions via the demonstrated differential functional connectivity. Our results indicate that early life stress may tip the neural balance toward acute threat responding and via that route predispose for affective disorder. SIGNIFICANCE STATEMENT Previously proposed differential contributions of the BNST and amygdala to fear and anxiety have been recently debated. Despite the significance of understanding their contributions to defensive reactions, there is a paucity of human studies that directly compared these regions on activity and connectivity during threat processing. We show strong evidence for a dissociable role of the BNST and amygdala in threat processing by demonstrating in two large participant samples that they show a distinct temporal signature of threat responding as well as a discriminable pattern of functional connections and differential sensitivity to early life threat. Copyright © 2017 the authors 0270-6474/17/379645-12$15.00/0.

Fear conditioning and extinction across development: evidence from human studies and animal models.

PubMed

Shechner, Tomer; Hong, Melanie; Britton, Jennifer C; Pine, Daniel S; Fox, Nathan A

2014-07-01

The ability to differentiate danger and safety through associative processes emerges early in life. Understanding the mechanisms underlying associative learning of threat and safety can clarify the processes that shape development of normative fears and pathological anxiety. Considerable research has used fear conditioning and extinction paradigms to delineate underlying mechanisms in animals and human adults; however, little is known about these mechanisms in children and adolescents. The current paper summarizes the empirical data on the development of fear conditioning and extinction. It reviews methodological considerations and future directions for research on fear conditioning and extinction in pediatric populations. Copyright © 2014 Elsevier B.V. All rights reserved.

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

Residual Expression of the Reprogramming Factors Prevents Differentiation of iPSC Generated from Human Fibroblasts and Cord Blood CD34+ Progenitors

PubMed Central

Ramos-Mejía, Verónica; Montes, Rosa; Bueno, Clara; Ayllón, Verónica; Real, Pedro J.; Rodríguez, René; Menendez, Pablo

2012-01-01

Human induced pluripotent stem cells (hiPSC) have been generated from different tissues, with the age of the donor, tissue source and specific cell type influencing the reprogramming process. Reprogramming hematopoietic progenitors to hiPSC may provide a very useful cellular system for modelling blood diseases. We report the generation and complete characterization of hiPSCs from human neonatal fibroblasts and cord blood (CB)-derived CD34+ hematopoietic progenitors using a single polycistronic lentiviral vector containing an excisable cassette encoding the four reprogramming factors Oct4, Klf4, Sox2 and c-myc (OKSM). The ectopic expression of OKSM was fully silenced upon reprogramming in some hiPSC clones and was not reactivated upon differentiation, whereas other hiPSC clones failed to silence the transgene expression, independently of the cell type/tissue origin. When hiPSC were induced to differentiate towards hematopoietic and neural lineages those hiPSC which had silenced OKSM ectopic expression displayed good hematopoietic and early neuroectoderm differentiation potential. In contrast, those hiPSC which failed to switch off OKSM expression were unable to differentiate towards either lineage, suggesting that the residual expression of the reprogramming factors functions as a developmental brake impairing hiPSC differentiation. Successful adenovirus-based Cre-mediated excision of the provirus OKSM cassette in CB-derived CD34+ hiPSC with residual transgene expression resulted in transgene-free hiPSC clones with significantly improved differentiation capacity. Overall, our findings confirm that residual expression of reprogramming factors impairs hiPSC differentiation. PMID:22545141

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

Hyperglycemia impedes definitive endoderm differentiation of human embryonic stem cells by modulating histone methylation patterns.

PubMed

Chen, A C H; Lee, Y L; Fong, S W; Wong, C C Y; Ng, E H Y; Yeung, W S B

2017-06-01

Exposure to maternal diabetes during fetal growth is a risk factor for the development of type II diabetes (T2D) in later life. Discovery of the mechanisms involved in this association should provide valuable background for therapeutic treatments. Early embryogenesis involves epigenetic changes including histone modifications. The bivalent histone methylation marks H3K4me3 and H3K27me3 are important for regulating key developmental genes during early fetal pancreas specification. We hypothesized that maternal hyperglycemia disrupted early pancreas development through changes in histone bivalency. A human embryonic stem cell line (VAL3) was used as the cell model for studying the effects of hyperglycemia upon differentiation into definitive endoderm (DE), an early stage of the pancreatic lineage. Hyperglycemic conditions significantly down-regulated the expression levels of DE markers SOX17, FOXA2, CXCR4 and EOMES during differentiation. This was associated with retention of the repressive histone methylation mark H3K27me3 on their promoters under hyperglycemic conditions. The disruption of histone methylation patterns was observed as early as the mesendoderm stage, with Wnt/β-catenin signaling being suppressed during hyperglycemia. Treatment with Wnt/β-catenin signaling activator CHIR-99021 restored the expression levels and chromatin methylation status of DE markers, even in a hyperglycemic environment. The disruption of DE development was also found in mouse embryos at day 7.5 post coitum from diabetic mothers. Furthermore, disruption of DE differentiation in VAL3 cells led to subsequent impairment in pancreatic progenitor formation. Thus, early exposure to hyperglycemic conditions hinders DE development with a possible relationship to the later impairment of pancreas specification.

NFκB signaling regulates embryonic and adult neurogenesis

PubMed Central

ZHANG, Yonggang; HU, Wenhui

2013-01-01

Both embryonic and adult neurogenesis involves the self-renewal/proliferation, survival, migration and lineage differentiation of neural stem/progenitor cells. Such dynamic process is tightly regulated by intrinsic and extrinsic factors and complex signaling pathways. Misregulated neurogenesis contributes much to a large range of neurodevelopmental defects and neurodegenerative diseases. The signaling of NFκB regulates many genes important in inflammation, immunity, cell survival and neural plasticity. During neurogenesis, NFκB signaling mediates the effect of numerous niche factors such as cytokines, chemokines, growth factors, extracellular matrix molecules, but also crosstalks with other signaling pathways such as Notch, Shh, Wnt/β-catenin. This review summarizes current progress on the NFκB signaling in all aspects of neurogenesis, focusing on the novel role of NFκB signaling in initiating early neural differentiation of neural stem cells and embryonic stem cells. PMID:24324484

Patterning of mammalian somites by surface ectoderm and notochord: evidence for sclerotome induction by a hedgehog homolog.

PubMed

Fan, C M; Tessier-Lavigne, M

1994-12-30

An early step in the development of vertebrae, ribs, muscle, and dermis is the differentiation of the somitic mesoderm into dermomyotome dorsally and sclerotome ventrally. To analyze this process, we have developed an in vitro assay for somitic mesoderm differentiation. We show that sclerotomal markers can be induced by a diffusible factor secreted by notochord and floor plate and that heterologous cells expressing Sonic hedgehog (shh/vhh-1) mimic this effect. In contrast, expression of dermomyotomal markers can be caused by a contact-dependent signal from surface ectoderm and a diffusible signal from dorsal neural tube. Our results extend previous studies by suggesting that dorsoventral patterning of somites involves the coordinate action of multiple dorsalizing and ventralizing signals and that a diffusible form of Shh/Vhh-1 mediates sclerotome induction.

The earth and the moon /Harold Jeffreys Lecture/.

NASA Technical Reports Server (NTRS)

Press, F.

1971-01-01

The internal structures of the earth and the moon are compared in the light of the latest extensive data on the earth structure, mobility of the earth outer layers, and the properties of lunar crust. The Monte Carlo method is applied to develop an earth model by a stepwise process beginning with a random distribution of two elastic velocities and the density as a function of de pth. Lunar seismic, magnetic, and rock analysis data are used to infer the properties of the moon. The marked planetological contrast between the earth and the moon is shown to consist in that the earth is highly differentiated and still undergoes a large-scale differentiation, while the moon has lost its volatiles in its early history and has a cold dynamically inactive shell which has been without basic changes for three billion years.

Interpersonal differentiation within depression diagnosis: relating interpersonal subgroups to symptom load and the quality of the early therapeutic alliance.

PubMed

Grosse Holtforth, Martin; Altenstein, David; Krieger, Tobias; Flückiger, Christoph; Wright, Aidan G C; Caspar, Franz

2014-01-01

We examined interpersonal problems in psychotherapy outpatients with a principal diagnosis of a depressive disorder in routine care (n=361). These patients were compared to a normative non-clinical sample and to outpatients with other principal diagnoses (n=959). Furthermore, these patients were statistically assigned to interpersonally defined subgroups that were compared regarding symptoms and the quality of the early alliance. The sample of depressive patients reported higher levels of interpersonal problems than the normative sample and the sample of outpatients without a principal diagnosis of depression. Latent Class Analysis identified eight distinct interpersonal subgroups, which differed regarding self-reported symptom load and the quality of the early alliance. However, therapists' alliance ratings did not differentiate between the groups. This interpersonal differentiation within the group of patients with a principal diagnosis of depression may add to a personalized psychotherapy based on interpersonal profiles.

Attachment affects social information processing: Specific electrophysiological effects of maternal stimuli.

PubMed

Wu, Lili; Gu, Ruolei; Zhang, Jianxin

2016-01-01

Attachment is critical to each individual. It affects the cognitive-affective processing of social information. The present study examines how attachment affects the processing of social information, specifically maternal information. We assessed the behavioral and electrophysiological responses to maternal information (compared to non-specific others) in a Go/No-go Association Task (GNAT) with 22 participants. The results illustrated that attachment affected maternal information processing during three sequential stages of information processing. First, attachment affected visual perception, reflected by enhanced P100 and N170 elicited by maternal information as compared to others information. Second, compared to others, mother obtained more attentional resources, reflected by faster behavioral response to maternal information and larger P200 and P300. Finally, mother was evaluated positively, reflected by shorter P300 latency in a mother + good condition as compared to a mother + bad condition. These findings indicated that the processing of attachment-relevant information is neurologically differentiated from other types of social information from an early stage of perceptual processing to late high-level processing.

Vesta Thermal Models

NASA Astrophysics Data System (ADS)

Formisano, M.; Federico, C.; Coradini, A.; Carli, C.; Turrini, D.

2011-12-01

Vesta is one of the largest Main Belt asteroid, considered the parent of the HED (Howardite - Eucrite - Diogenite) meteorites. Spectroscopic studies in fact show the presence of the 0.9 and 1.9 μm absorption bands for pyroxene in the spectra of Vesta that match those observed in the spectra of HED meteorites (see Gaffey, 1997, Surface Lihologic Heterogeneity of Asteroid 4 Vesta, Icarus, 127). The spectral connection between Vesta and the Howardite-Eurcrite-Diogenite (HED) suite of meteorites suggests that Vesta formed very early in the history of the Solar System and differentiated on a Ma-long timescale due to the decay of short-lived radioactive nuclides (see Keil K., 2002, Geological History of Asteroid 4 Vesta: The Smallest Terrestrial Planet. Asteroids III, and references therein). The importance of studying the thermal evolution of Vesta is therefore linked to the understanding of the processes of core and crust formation in planetary bodies so Vesta can be considered a good model for the primordial stages of the terrestrial planets. Our interest is mainly focused on the study of different energy sources, and how they contribute to differentiation and, more generally, to the thermal history of the body. We analyze not only the contribution of short-lived radionuclides, i.e. 26Al and 60Fe, but also the contribution of long-lived radionuclides, in particular 40K, 232Th, 235U and 238U, and that of accretional heating. The contribution of the long-lived radionuclides does not change the overall thermal history but it only slows down the cooling of the body. We have also observed that the effect of the accretional heating is limited if not negligible: in the most favourable scenarios its contribution only raise the starting temperature of the body but it is not sufficient to start the differentiation process. Vesta thermal and structural evolution is therefore characterized by the contribution of the short-lived radionuclides. The scenarios we considered differ in the time delay Δt. The time delay Δt is a parameter that takes into account not only the uncertainties due to the injection of 26Al in the Solar Nebula, but also the uncertainties linked to the time of the accretional process of Vesta. In all the scenarios we observe the differentiation of the body, i.e. the formation of a metallic core (mainly iron) and a silicatic crust of which we discuss the chemical and physical evolution, in particular by analyzing the link with the Jovian Early Bombardment phase ( D.Turrini, G.Magni, A.Coradini, 2011, Probing the history of Solar System through the cratering records on Vesta and Ceres, MNRAS, DOI: 10.1111/j.1365-2966.2011.18316.x). We also preliminarly discuss the heat released by the impacts during the Jovian Early Bombardment phase and their possible contribution to the thermal history of Vesta.

Fucoxanthin exerts differing effects on 3T3-L1 cells according to differentiation stage and inhibits glucose uptake in mature adipocytes

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

Kang, Seong-Il; Ko, Hee-Chul; Shin, Hye-Sun

2011-06-17

Highlights: {yields} Fucoxanthin enhances 3T3-L1 adipocyte differentiation at an early stage. {yields} Fucoxanthin inhibits 3T3-L1 adipocyte differentiation at intermediate and late stages. {yields} Fucoxanthin attenuates glucose uptake by inhibiting the phosphorylation of IRS in mature 3T3-L1 adipocytes. {yields} Fucoxanthin exerts its anti-obesity effect by inhibiting the differentiation of adipocytes at both intermediate and late stages, as well as glucose uptake in mature adipocytes. -- Abstract: Progression of 3T3-L1 preadipocyte differentiation is divided into early (days 0-2, D0-D2), intermediate (days 2-4, D2-D4), and late stages (day 4 onwards, D4-). In this study, we investigated the effects of fucoxanthin, isolated from themore » edible brown seaweed Petalonia binghamiae, on adipogenesis during the three differentiation stages of 3T3-L1 preadipocytes. When fucoxanthin was applied during the early stage of differentiation (D0-D2), it promoted 3T3-L1 adipocyte differentiation, as evidenced by increased triglyceride accumulation. At the molecular level, fucoxanthin increased protein expression of peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}), CCAAT/enhancer-binding protein {alpha} (C/EBP{alpha}), sterol regulatory element-binding protein 1c (SREBP1c), and aP2, and adiponectin mRNA expression, in a dose-dependent manner. However, it reduced the expression of PPAR{gamma}, C/EBP{alpha}, and SREBP1c during the intermediate (D2-D4) and late stages (D4-D7) of differentiation. It also inhibited the uptake of glucose in mature 3T3-L1 adipocytes by reducing the phosphorylation of insulin receptor substrate 1 (IRS-1). These results suggest that fucoxanthin exerts differing effects on 3T3-L1 cells of different differentiation stages and inhibits glucose uptake in mature adipocytes.« less

Top-down beta oscillatory signaling conveys behavioral context in early visual cortex.

PubMed

Richter, Craig G; Coppola, Richard; Bressler, Steven L

2018-05-03

Top-down modulation of sensory processing is a critical neural mechanism subserving numerous important cognitive roles, one of which may be to inform lower-order sensory systems of the current 'task at hand' by conveying behavioral context to these systems. Accumulating evidence indicates that top-down cortical influences are carried by directed interareal synchronization of oscillatory neuronal populations, with recent results pointing to beta-frequency oscillations as particularly important for top-down processing. However, it remains to be determined if top-down beta-frequency oscillations indeed convey behavioral context. We measured spectral Granger Causality (sGC) using local field potentials recorded from microelectrodes chronically implanted in visual areas V1/V2, V4, and TEO of two rhesus macaque monkeys, and applied multivariate pattern analysis to the spatial patterns of top-down sGC. We decoded behavioral context by discriminating patterns of top-down (V4/TEO-to-V1/V2) beta-peak sGC for two different task rules governing correct responses to identical visual stimuli. The results indicate that top-down directed influences are carried to visual cortex by beta oscillations, and differentiate task demands even before visual stimulus processing. They suggest that top-down beta-frequency oscillatory processes coordinate processing of sensory information by conveying global knowledge states to early levels of the sensory cortical hierarchy independently of bottom-up stimulus-driven processing.

Bit-1 is an essential regulator of myogenic differentiation

PubMed Central

Griffiths, Genevieve S.; Doe, Jinger; Jijiwa, Mayumi; Van Ry, Pam; Cruz, Vivian; de la Vega, Michelle; Ramos, Joe W.; Burkin, Dean J.; Matter, Michelle L.

2015-01-01

Muscle differentiation requires a complex signaling cascade that leads to the production of multinucleated myofibers. Genes regulating the intrinsic mitochondrial apoptotic pathway also function in controlling cell differentiation. How such signaling pathways are regulated during differentiation is not fully understood. Bit-1 (also known as PTRH2) mutations in humans cause infantile-onset multisystem disease with muscle weakness. We demonstrate here that Bit-1 controls skeletal myogenesis through a caspase-mediated signaling pathway. Bit-1-null mice exhibit a myopathy with hypotrophic myofibers. Bit-1-null myoblasts prematurely express muscle-specific proteins. Similarly, knockdown of Bit-1 expression in C2C12 myoblasts promotes early differentiation, whereas overexpression delays differentiation. In wild-type mice, Bit-1 levels increase during differentiation. Bit-1-null myoblasts exhibited increased levels of caspase 9 and caspase 3 without increased apoptosis. Bit-1 re-expression partially rescued differentiation. In Bit-1-null muscle, Bcl-2 levels are reduced, suggesting that Bcl-2-mediated inhibition of caspase 9 and caspase 3 is decreased. Bcl-2 re-expression rescued Bit-1-mediated early differentiation in Bit-1-null myoblasts and C2C12 cells with knockdown of Bit-1 expression. These results support an unanticipated yet essential role for Bit-1 in controlling myogenesis through regulation of Bcl-2. PMID:25770104

Abdullah's Genuine Indonesian Curry Powder--about Early Readers and Differentiated Teaching.

ERIC Educational Resources Information Center

Hansen, Vagn Rabol; Robenhagen, Ole

A study established some characteristics of early readers and their homes and families, how they learned to read, and how their surroundings, and particularly the school, reacted. Approximately 300 Danish early readers and their families were interviewed and completed questionnaires. Results indicated that: (1) half the early readers had either a…

Prefrontal mRNA expression of long and short isoforms of D2 dopamine receptor: Possible role in delayed learning deficit caused by early life interleukin-1β treatment.

PubMed

Schwarz, Alexander P; Trofimov, Alexander N; Zubareva, Olga E; Lioudyno, Victoria I; Kosheverova, Vera V; Ischenko, Alexander M; Klimenko, Victor M

2017-08-30

Long (D2L) and short (D2S) isoform of the D2 dopamine receptor are believed to play different roles in behavioral regulation. However, little is known about differential regulation of these isoforms mRNA expression during the process of learning in physiological and pathological states. In this study, we have investigated the combined effect of training in active avoidance (AA) paradigm and chronic early life treatment with pro-inflammatory cytokine interleukin (IL)-1β (1μg/kg i.p., P15-21) on D2S and D2L dopamine receptor mRNA expression in the medial prefrontal cortex (mPFC) of adult rats. We have shown differential regulation of D2 short and long mRNA isoform expression in the mPFC. There was no effect of AA-training on D2S mRNA expression, while D2L mRNA was downregulated in AA-trained control (intact and saline-treated) animals, and this effect was not observed in rats treated with IL-1β. D2S mRNA expression level negatively correlated with learning ability within control (saline-treated and intact) groups but not in IL-1β-treated animals. Thus, prefrontal expression of distinct D2 dopamine receptor splice variants is supposed to be implicated in cognitive decline caused by early life immune challenge. Copyright © 2017 Elsevier B.V. All rights reserved.

Profiling analysis of long non-coding RNAs in early postnatal mouse hearts

PubMed Central

Sun, Xiongshan; Han, Qi; Luo, Hongqin; Pan, Xiaodong; Ji, Yan; Yang, Yao; Chen, Hanying; Wang, Fangjie; Lai, Wenjing; Guan, Xiao; Zhang, Qi; Tang, Yuan; Chu, Jianhong; Yu, Jianhua; Shou, Weinian; Deng, Youcai; Li, Xiaohui

2017-01-01

Mammalian cardiomyocytes undergo a critical hyperplastic-to-hypertrophic growth transition at early postnatal age, which is important in establishing normal physiological function of postnatal hearts. In the current study, we intended to explore the role of long non-coding (lnc) RNAs in this transitional stage. We analyzed lncRNA expression profiles in mouse hearts at postnatal day (P) 1, P7 and P28 via microarray. We identified 1,146 differentially expressed lncRNAs with more than 2.0-fold change when compared the expression profiles of P1 to P7, P1 to P28, and P7 to P28. The neighboring genes of these differentially expressed lncRNAs were mainly involved in DNA replication-associated biological processes. We were particularly interested in one novel cardiac-enriched lncRNA, ENSMUST00000117266, whose expression was dramatically down-regulated from P1 to P28 and was also sensitive to hypoxia, paraquat, and myocardial infarction. Knockdown ENSMUST00000117266 led to a significant increase of neonatal mouse cardiomyocytes in G0/G1 phase and reduction in G2/M phase, suggesting that ENSMUST00000117266 is involved in regulating cardiomyocyte proliferative activity and is likely associated with hyperplastic-to-hypertrophic growth transition. In conclusion, our data have identified a large group of lncRNAs presented in the early postnatal mouse heart. Some of these lncRNAs may have important functions in cardiac hyperplastic-to-hypertrophic growth transition. PMID:28266538

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.

Calcium sources used by post-natal human myoblasts during initial differentiation.

PubMed

Arnaudeau, Serge; Holzer, Nicolas; König, Stéphane; Bader, Charles R; Bernheim, Laurent

2006-08-01

Increases in cytoplasmic Ca(2+) are crucial for inducing the initial steps of myoblast differentiation that ultimately lead to fusion; yet the mechanisms that produce this elevated Ca(2+) have not been fully resolved. For example, it is still unclear whether the increase comes exclusively from membrane Ca(2+) influx or also from Ca(2+) release from internal stores. To address this, we investigated early differentiation of myoblast clones each derived from single post-natal human satellite cells. Initial differentiation was assayed by immunostaining myonuclei for the transcription factor MEF2. When Ca(2+) influx was eliminated by using low external Ca(2+) media, we found that approximately half the clones could still differentiate. Of the clones that required influx of external Ca(2+), most clones used T-type Ca(2+) channels, but others used store-operated channels as influx-generating mechanisms. On the other hand, clones that differentiated in low external Ca(2+) relied on Ca(2+) release from internal stores through IP(3) receptors. Interestingly, by following clones over time, we observed that some switched their preferred Ca(2+) source: clones that initially used calcium release from internal stores to differentiate later required Ca(2+) influx and inversely. In conclusion, we show that human myoblasts can use three alternative mechanisms to increase cytoplasmic Ca(2+) at the onset of the differentiation process: influx through T-types Ca(2+) channels, influx through store operated channels and release from internal stores through IP(3) receptors. In addition, we suggest that, probably because Ca(2+) elevation is essential during initial differentiation, myoblasts may be able to select between these alternate Ca(2+) pathways.

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

Persimmon tannin represses 3T3-L1 preadipocyte differentiation via up-regulating expression of miR-27 and down-regulating expression of peroxisome proliferator-activated receptor-γ in the early phase of adipogenesis.

PubMed

Zou, Bo; Ge, Zhenzhen; Zhu, Wei; Xu, Ze; Li, Chunmei

2015-12-01

Currently, obesity has become a worldwide health problem. Adipocyte differentiation is closely associated with the onset of obesity. Our previous studies suggested that persimmon tannin might be a potent anti-adipogenic dietary bioactive compound. However, the mechanism of persimmon tannin on adipocyte differentiation is still unknown. The purpose of this study was to investigate the effect of persimmon tannin on adipogenic differentiation in 3T3-L1 preadipocytes and the underlying mechanisms. Adipogenic differentiation was induced by cocktail in the presence or absence of persimmon tannin. Intracellular lipid accumulation was determined by Oil red O staining and enzymatic colorimetric methods. Gene expression and protein levels were measured by real time RT-PCR and Western blot. Persimmon tannin inhibited intracellular lipid accumulation markedly, and the inhibitory effect was largely limited to the early stage of adipocyte differentiation. Persimmon tannin suppressed the expression of C/EBPα and peroxisome proliferator-activated receptor-γ (PPARγ), significantly. Furthermore, genes related to lipogenesis, such as sterol regulatory element-binding protein 1, were down-regulated by persimmon tannin. In addition, adipocyte fatty acid binding protein (aP2), which is a target gene of PPARγ, was suppressed by persimmon tannin notably. Correspondingly, the expression of miR-27a and miR-27b were up-regulated by persimmon tannin from Day 2 to Day 8 significantly. Persimmon tannin inhibited adipocyte differentiation through regulation of PPARγ, C/EBPα and miR-27 in early stage of adipogenesis.

Production of Solar Cells in Space from Non Specific Ores by Utilization of Electronically Enhanced Sputtering

NASA Technical Reports Server (NTRS)

Curreri, Peter A.

2009-01-01

An ideal method of construction in space would utilize some form of the Universal Differentiator and Universal Constructor as described by Von Neumann (1). The Universal Differentiator is an idealized non ore specific extractive device which is capable of breaking any ore into its constituent elements, and the Universal Constructor can utilize these elements to build any device with controllability to the nanometer scale. During the Human Exploration Initiative program in the early 1990s a conceptual study was done (2) to understand whether such devices were feasible with near term technology for the utilization of space resources and energy. A candidate system was proposed which would utilize electronically enhanced sputtering as the differentiator. Highly ionized ions would be accelerated to a kinetic energy at which the interaction between them and the lattice elections in the ore would be at a maximum. Experiments have shown that the maximum disintegration of raw material occurs at an ion kinetic energy of about 5 MeV, regardless of the composition and structure of the raw material. Devices that could produce charged ion beams in this energy range in space were being tested in the early 1990s. At this energy, for example an ion in a beam of fluorine ions yields about 8 uranium ions from uranium fluoride, 1,400 hydrogen and oxygen atoms from ice, or 7,000 atoms from sulfur dioxide ice. The ions from the disintegrated ore would then be driven by an electrical field into a discriminator in the form of a mass spectrometer, where the magnetic field would divert the ions into collectors for future use or used directly in molecular beam construction techniques. The process would require 10-7 Torr vacuum which would be available in space or on the moon. If the process were used to make thin film silicon solar cells (ignoring any energy inefficiency for beam production), then energy break even for solar cells in space would occur after 14 days.

Event-related potentials when identifying or color-naming threatening schematic stimuli in spider phobic and non-phobic individuals

PubMed Central

Kolassa, Iris-Tatjana; Musial, Frauke; Kolassa, Stephan; Miltner, Wolfgang HR

2006-01-01

Background Previous studies revealed increased parietal late positive potentials (LPPs) in response to spider pictures in spider phobic individuals. This study searched for basic features of fear-relevant stimuli by investigating whether schematic spider images are sufficient to evoke differential behavioral as well as differential early and late ERP responses in spider phobic, social phobic (as a clinical control group), and non-phobic control participants. Methods Behavioral and electrophysiological correlates of the processing of schematic spider and flower images were investigated while participants performed a color (emotional Stroop) and an object identification task. Stimuli were schematic pictures of spiders and flowers matched with respect to constituting visual elements. Results Consistent with previous studies using photographic spider pictures, spider phobic persons showed enhanced LPPs when identifying schematic spiders compared to schematic flowers. In addition, spider phobic individuals showed generally faster responses than the control groups. This effect was interpreted as evidence for an increased general behavioral hypervigilance in this anxiety disorder group. Furthermore, both phobic groups showed enhanced P100 amplitudes compared to controls, which was interpreted as evidence for an increased (cortical) hypervigilance for incoming stimuli in phobic patients in general. Finally, all groups showed faster identification of and larger N170 amplitudes in response to schematic spider than flower pictures. This may reflect either a general advantage for fear-relevant compared to neutral stimuli, or might be due to a higher level of expertise in processing schematic spiders as compared to the more artificially looking flower stimuli. Conclusion Results suggest that schematic spiders are sufficient to prompt differential responses in spider-fearful and spider-non-fearful persons in late ERP components. Early ERP components, on the other hand, seem to be modified by anxiety status per se, which is consistent with recent theories on general hypervigilance in the anxiety disorder spectrum. PMID:16981991

Selective Roles of Normal and Mutant Huntingtin in Neural Induction and Early Neurogenesis

PubMed Central

Nguyen, Giang D.; Gokhan, Solen; Molero, Aldrin E.; Mehler, Mark F.

2013-01-01

Huntington's disease (HD) is a neurodegenerative disorder caused by abnormal polyglutamine expansion in the amino-terminal end of the huntingtin protein (Htt) and characterized by progressive striatal and cortical pathology. Previous reports have shown that Htt is essential for embryogenesis, and a recent study by our group revealed that the pathogenic form of Htt (mHtt) causes impairments in multiple stages of striatal development. In this study, we have examined whether HD-associated striatal developmental deficits are reflective of earlier maturational alterations occurring at the time of neurulation by assessing differential roles of Htt and mHtt during neural induction and early neurogenesis using an in vitro mouse embryonic stem cell (ESC) clonal assay system. We demonstrated that the loss of Htt in ESCs (KO ESCs) severely disrupts the specification of primitive and definitive neural stem cells (pNSCs, dNSCs, respectively) during the process of neural induction. In addition, clonally derived KO pNSCs and dNSCs displayed impaired proliferative potential, enhanced cell death and altered multi-lineage potential. Conversely, as observed in HD knock-in ESCs (Q111 ESCs), mHtt enhanced the number and size of pNSC clones, which exhibited enhanced proliferative potential and precocious neuronal differentiation. The transition from Q111 pNSCs to fibroblast growth factor 2 (FGF2)-responsive dNSCs was marked by potentiation in the number of dNSCs and altered proliferative potential. The multi-lineage potential of Q111 dNSCs was also enhanced with precocious neurogenesis and oligodendrocyte progenitor elaboration. The generation of Q111 epidermal growth factor (EGF)-responsive dNSCs was also compromised, whereas their multi-lineage potential was unaltered. These abnormalities in neural induction were associated with differential alterations in the expression profiles of Notch, Hes1 and Hes5. These cumulative observations indicate that Htt is required for multiple stages of neural induction, whereas mHtt enhances this process and promotes precocious neurogenesis and oligodendrocyte progenitor cell elaboration. PMID:23691206

Event-related potentials when identifying or color-naming threatening schematic stimuli in spider phobic and non-phobic individuals.

PubMed

Kolassa, Iris-Tatjana; Musial, Frauke; Kolassa, Stephan; Miltner, Wolfgang H R

2006-09-18

Previous studies revealed increased parietal late positive potentials (LPPs) in response to spider pictures in spider phobic individuals. This study searched for basic features of fear-relevant stimuli by investigating whether schematic spider images are sufficient to evoke differential behavioral as well as differential early and late ERP responses in spider phobic, social phobic (as a clinical control group), and non-phobic control participants. Behavioral and electrophysiological correlates of the processing of schematic spider and flower images were investigated while participants performed a color (emotional Stroop) and an object identification task. Stimuli were schematic pictures of spiders and flowers matched with respect to constituting visual elements. Consistent with previous studies using photographic spider pictures, spider phobic persons showed enhanced LPPs when identifying schematic spiders compared to schematic flowers. In addition, spider phobic individuals showed generally faster responses than the control groups. This effect was interpreted as evidence for an increased general behavioral hypervigilance in this anxiety disorder group. Furthermore, both phobic groups showed enhanced P100 amplitudes compared to controls, which was interpreted as evidence for an increased (cortical) hypervigilance for incoming stimuli in phobic patients in general. Finally, all groups showed faster identification of and larger N170 amplitudes in response to schematic spider than flower pictures. This may reflect either a general advantage for fear-relevant compared to neutral stimuli, or might be due to a higher level of expertise in processing schematic spiders as compared to the more artificially looking flower stimuli. Results suggest that schematic spiders are sufficient to prompt differential responses in spider-fearful and spider-non-fearful persons in late ERP components. Early ERP components, on the other hand, seem to be modified by anxiety status per se, which is consistent with recent theories on general hypervigilance in the anxiety disorder spectrum.

Identification of MS4A3 as a reliable marker for early myeloid differentiation in human hematopoiesis.

PubMed

Ishibashi, Tomohiko; Yokota, Takafumi; Satoh, Yusuke; Ichii, Michiko; Sudo, Takao; Doi, Yukiko; Ueda, Tomoaki; Nagate, Yasuhiro; Hamanaka, Yuri; Tanimura, Akira; Ezoe, Sachiko; Shibayama, Hirohiko; Oritani, Kenji; Kanakura, Yuzuru

2018-01-15

Information of myeloid lineage-related antigen on hematopoietic stem/progenitor cells (HSPCs) is important to clarify the mechanisms regulating hematopoiesis, as well as for the diagnosis and treatment of myeloid malignancies. We previously reported that special AT-rich sequence binding protein 1 (SATB1), a global chromatin organizer, promotes lymphoid differentiation from HSPCs. To search a novel cell surface molecule discriminating early myeloid and lymphoid differentiation, we performed microarray analyses comparing SATB1-overexpressed HSPCs with mock-transduced HSPCs. The results drew our attention to membrane-spanning 4-domains, subfamily A, member 3 (Ms4a3) as the most downregulated molecule in HSPCs with forced overexpression of SATB1. Ms4a3 expression was undetectable in hematopoietic stem cells, but showed a concomitant increase with progressive myeloid differentiation, whereas not only lymphoid but also megakaryocytic-erythrocytic progenitors were entirely devoid of Ms4a3 expression. Further analysis revealed that a subset of CD34 + CD38 + CD33 + progenitor population in human adult bone marrow expressed MS4A3, and those MS4A3 + progenitors only produced granulocyte/macrophage colonies, losing erythroid colony- and mixed colony-forming capacity. These results suggest that cell surface expression of MS4A3 is useful to distinguish granulocyte/macrophage lineage-committed progenitors from other lineage-related ones in early human hematopoiesis. In conclusion, MS4A3 is useful to monitor early stage of myeloid differentiation in human hematopoiesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Redefining early gastric cancer.

PubMed

Barreto, Savio G; Windsor, John A

2016-01-01

The problem is that current definitions of early gastric cancer allow the inclusion of regional lymph node metastases. The increasing use of endoscopic submucosal dissection to treat early gastric cancer is a concern because regional lymph nodes are not addressed. The aim of the study was thus to critically evaluate current evidence with regard to tumour-specific factors associated with lymph node metastases in "early gastric cancer" to develop a more precise definition and improve clinical management. A systematic and comprehensive search of major reference databases (MEDLINE, EMBASE, PubMed and the Cochrane Library) was undertaken using a combination of text words "early gastric cancer", "lymph node metastasis", "factors", "endoscopy", "surgery", "lymphadenectomy" "mucosa", "submucosa", "lymphovascular invasion", "differentiated", "undifferentiated" and "ulcer". All available publications that described tumour-related factors associated with lymph node metastases in early gastric cancer were included. The initial search yielded 1494 studies, of which 42 studies were included in the final analysis. Over time, the definition of early gastric cancer has broadened and the indications for endoscopic treatment have widened. The mean frequency of lymph node metastases increased on the basis of depth of infiltration (mucosa 6% vs. submucosa 28%), presence of lymphovascular invasion (absence 9% vs. presence 53%), tumour differentiation (differentiated 13% vs. undifferentiated 34%) and macroscopic type (elevated 13% vs. flat 26%) and tumour diameter (≤2 cm 8% vs. >2 cm 25%). There is a need to re-examine the diagnosis and staging of early gastric cancer to ensure that patients with one or more identifiable risk factor for lymph node metastases are not denied appropriate chemotherapy and surgical resection.

The heartstrings mutation in zebrafish causes heart/fin Tbx5 deficiency syndrome.

PubMed

Garrity, Deborah M; Childs, Sarah; Fishman, Mark C

2002-10-01

Holt-Oram syndrome is one of the autosomal dominant human "heart-hand" disorders, with a combination of upper limb malformations and cardiac defects. Holt-Oram syndrome is caused by mutations in the TBX5 gene, a member of a large family of T-box transcription factors that play important roles in cell-type specification and morphogenesis. In a screen for mutations affecting zebrafish cardiac function, we isolated the recessive lethal mutant heartstrings, which lacks pectoral fins and exhibits severe cardiac dysfunction, beginning with a slow heart rate and progressing to a stretched, non-functional heart. We mapped and cloned the heartstrings mutation and find it to encode the zebrafish ortholog of the TBX5 gene. The heartstrings mutation causes premature termination at amino acid 316. Homozygous mutant embryos never develop pectoral fin buds and do not express several markers of early fin differentiation. The total absence of any fin bud differentiation distinguishes heartstrings from most other mutations that affect zebrafish fin development, suggesting that Tbx5 functions very early in the pectoral fin induction pathway. Moderate reduction of Tbx5 by morpholino causes fin malformations, revealing an additional early requirement for Tbx5 in coordinating the axes of fin outgrowth. The heart of heartstrings mutant embryos appears to form and function normally through the early heart tube stage, manifesting only a slight bradycardia compared with wild-type siblings. However, the heart fails to loop and then progressively deteriorates, a process affecting the ventricle as well as the atrium. Relative to mammals, fish require lower levels of Tbx5 to produce malformed appendages and display whole-heart rather than atrial-predominant cardiac defects. However, the syndromic deficiencies of tbx5 mutation are remarkably well retained between fish and mammals.

Ceres Evolution: From Thermodynamic Modeling and Now Dawn Observation

NASA Astrophysics Data System (ADS)

McCord, T. B.; Combe, J. P.; Castillo, J. C.; Raymond, C. A.; De Sanctis, M. C.; Jaumann, R.; Ammannito, E.; Russell, C. T.

2015-12-01

Thermodynamic modeling indicated that Ceres has experienced planetary processes, including extensive melting of its ~25% water and differentiation, (McCord and Sotin, JGR, 2005; Castillo and McCord, Icarus, 2009). Early telescopic studies showed Ceres' surface to be spectrally similar to carboneous-chondrite-like material, i.e., aqueously altered silicates darkened by carbon, with a water-OH-related absorption near 3.06 µm. Later observations improved the spectra and suggested more specific interpretations: Structural water in clay minerals, phyllosilicates, perhaps ammoniated, iron-rich clays, carbonates, brucite, all implying extensive aqueous alteration, perhaps in the presence of CO2. Telescopic observations and thermodynamic models predicted Dawn would find a very different body compared to Vesta (e.g. McCord et al., SSR, 2011), as current Dawn observations are confirming. Ceres' original water ice should have melted early in its evolution, with the resulting differentiation and mineralization strongly affecting Ceres' composition, size and shape over time. The ocean should have become very salty and perhaps may still be liquid in places. The surface composition from telescopes seems to reflect this complex history. The mineralization with repeated mixing of the crust with the early liquid interior and with in-fall from space would create a complex surface that will present an interpretation challenge for Dawn. The Dawn spacecraft is currently collecting observations of Ceres' landforms, elemental and mineralogical/molecular composition and gravity field from orbit. Early results suggest a heavily cratered but distorted and lumpy body with features and composition consistent with internal activity, perhaps recent or current, associated with water and perhaps other volatiles. We will present and interpret the latest Dawn Ceres findings and how they affect our earlier understanding of Ceres evolution from modeling and telescope observations.

Validation of the early childhood attitude toward women in science scale (ECWiSS): A pilot administration

NASA Astrophysics Data System (ADS)

Mulkey, Lynn M.

The intention of this research was to measure attitudes of young children toward women scientists. A 27-item instrument, the Early Childhood Women in Science Scale (ECWiSS) was validated in a test case of the proposition that differential socialization predicts entry into the scientific talent pool. Estimates of internal consistency indicated that the scale is highly reliable. Known groups and correlates procedures, employed to determine the validity of the instrument, revealed that the scale is able to discriminate significant differences between groups and distinguishes three dimensions of attitude (role-specific self-concept, home-related sex-role conflict, and work-related sex-role conflict). Results of the analyses also confirmed the anticipated pattern of correlations with measures of another construct. The findings suggest the utility of the ECWiSS for measurement of early childhood attitudes in models of the ascriptive and/or meritocratic processes affecting recruitment to science and more generally in program and curriculum evaluation where attitude toward women in science is the construct of interest.

Volatile inventory of Mars-2: Primordial sources and fractionating processes

NASA Technical Reports Server (NTRS)

Pepin, R. O.

1987-01-01

The total volatile inventory of Mars has been modeled using meteoritic and presumed primordial abundances in the early solar system. Evidence is presented which indicates that the elemental abundances of the noble gases on Earth and Mars are similar, and their ratios are comparable to those in average carbonaceous chondrites with the exception of xenon and krypton. In order to account for presently observed variations in gas abundances, two primordial sources were used. One was the solar composition similar to the solar wind, and the other of carbonaceous grains that were the source for trace exotic components. For Mars, a model in which the early, high solar EUV flux with continued hydrogen production by differentiation results in mass fractionation of the primordial atmosphere, early depletion of xenon, and later depletion of gases lighter than krypton. The result is that the primordial Mars water inventory may have been on the order of 20 to 30 km if spread over the planet.

Dynamic switching between semantic and episodic memory systems.

PubMed

Kompus, Kristiina; Olsson, Carl-Johan; Larsson, Anne; Nyberg, Lars

2009-09-01

It has been suggested that episodic and semantic long-term memory systems interact during retrieval. Here we examined the flexibility of memory retrieval in an associative task taxing memories of different strength, assumed to differentially engage episodic and semantic memory. Healthy volunteers were pre-trained on a set of 36 face-name pairs over a 6-week period. Another set of 36 items was shown only once during the same time period. About 3 months after the training period all items were presented in a randomly intermixed order in an event-related fMRI study of face-name memory. Once presented items differentially activated anterior cingulate cortex and a right prefrontal region that previously have been associated with episodic retrieval mode. High-familiar items were associated with stronger activation of posterior cortices and a left frontal region. These findings fit a model of memory retrieval by which early processes determine, on a trial-by-trial basis, if the task can be solved by the default semantic system. If not, there is a dynamic shift to cognitive control processes that guide retrieval from episodic memory.

In vivo optical coherence tomography of human skin microstructure

NASA Astrophysics Data System (ADS)

Sergeev, Alexander M.; Gelikonov, Valentin M.; Gelikonov, Grigory V.; Feldchtein, Felix I.; Pravdenko, Kirill I.; Shabanov, Dmitry V.; Gladkova, Natalia D.; Pochinko, Vitaly; Zhegalov, V.; Dmitriev, G.; Vazina, I.; Petrova, Galina P.; Nikulin, Nikolai K.

1994-12-01

A compact effective optical coherence tomography (OCT) system is presented. It contains approximately equals 0.3 mW superluminescent diode with spectral width 30 nm FWHM (providing approximately equals 15 micrometers longitudinal resolution) and fiber interferometer with integrated longitudinal scanning. The dynamic range 60 dB allows to observe structure of human skin in vivo up to 1.5 mm in depth. A comparison of obtained tomographs with data of histologic analysis of the same samples of the skin have been carried out to identify the observed structures and determine their optical properties. This technique allows one to perform noncontact, noninvasive diagnostic of early stages of different pathological state of the skin, to measure the burn depth and to observe the process of the recovery. Unlike scanning confocal microscopy, OCT is more suitable for an endoscopic investigation of the mucous membranes of hollow organs. Possible diagnostic applications include dermatology, gastroenterology, gynecology, urology, oncology, othorinolaryngology, transplantology. The most promising features are the potential possibility of differential diagnosis of precancer and various types of cancer, estimation of the invasion depth, differential diagnosis of inflammation and dystrophic processes, control of radical operative treatment.

Active tissue stiffness modulation controls valve interstitial cell phenotype and osteogenic potential in 3D culture.

PubMed

Duan, Bin; Yin, Ziying; Hockaday Kang, Laura; Magin, Richard L; Butcher, Jonathan T

2016-05-01

Calcific aortic valve disease (CAVD) progression is a highly dynamic process whereby normally fibroblastic valve interstitial cells (VIC) undergo osteogenic differentiation, maladaptive extracellular matrix (ECM) composition, structural remodeling, and tissue matrix stiffening. However, how VIC with different phenotypes dynamically affect matrix properties and how the altered matrix further affects VIC phenotypes in response to physiological and pathological conditions have not yet been determined. In this study, we develop 3D hydrogels with tunable matrix stiffness to investigate the dynamic interplay between VIC phenotypes and matrix biomechanics. We find that VIC populated within hydrogels with valve leaflet like stiffness differentiate towards myofibroblasts in osteogenic media, but surprisingly undergo osteogenic differentiation when cultured within lower initial stiffness hydrogels. VIC differentiation progressively stiffens the hydrogel microenvironment, which further upregulates both early and late osteogenic markers. These findings identify a dynamic positive feedback loop that governs acceleration of VIC calcification. Temporal stiffening of pathologically lower stiffness matrix back to normal level, or blocking the mechanosensitive RhoA/ROCK signaling pathway, delays the osteogenic differentiation process. Therefore, direct ECM biomechanical modulation can affect VIC phenotypes towards and against osteogenic differentiation in 3D culture. These findings highlight the importance of the homeostatic maintenance of matrix stiffness to restrict pathological VIC differentiation. We implement 3D hydrogels with tunable matrix stiffness to investigate the dynamic interaction between valve interstitial cells (VIC, major cell population in heart valve) and matrix biomechanics. This work focuses on how human VIC responses to changing 3D culture environments. Our findings identify a dynamic positive feedback loop that governs acceleration of VIC calcification, which is the hallmark of calcific aortic valve disease. Temporal stiffening of pathologically lower stiffness matrix back to normal level, or blocking the mechanosensitive signaling pathway, delays VIC osteogenic differentiation. Our findings provide an improved understanding of VIC-matrix interactions to aid in interpretation of VIC calcification studies in vitro and suggest that ECM disruption resulting in local tissue stiffness decreases may promote calcific aortic valve disease. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

COBE DMR results and implications. [Differential Microwave Radiometer

NASA Technical Reports Server (NTRS)

Smoot, George F.

1992-01-01

This lecture presents early results obtained from the first six months of measurements of the Cosmic Microwave Background (CMB) by Differential Microwave Radiometers (DMR) aboard COBE and discusses significant cosmological implications. The DMR maps show the dipole anisotropy and some galactic emission but otherwise a spatially smooth early universe. The measurements are sufficiently precise that we must pay careful attention to potential systematic errors. Maps of galactic and local emission such as those produced by the FIRAS and DIRBE instruments will be needed to identify foregrounds from extragalactic emission and thus to interpret the results in terms of events in the early universe. The current DMR results are significant for Cosmology.

Sensory Contributions to Impaired Emotion Processing in Schizophrenia

PubMed Central

Butler, Pamela D.; Abeles, Ilana Y.; Weiskopf, Nicole G.; Tambini, Arielle; Jalbrzikowski, Maria; Legatt, Michael E.; Zemon, Vance; Loughead, James; Gur, Ruben C.; Javitt, Daniel C.

2009-01-01

Both emotion and visual processing deficits are documented in schizophrenia, and preferential magnocellular visual pathway dysfunction has been reported in several studies. This study examined the contribution to emotion-processing deficits of magnocellular and parvocellular visual pathway function, based on stimulus properties and shape of contrast response functions. Experiment 1 examined the relationship between contrast sensitivity to magnocellular- and parvocellular-biased stimuli and emotion recognition using the Penn Emotion Recognition (ER-40) and Emotion Differentiation (EMODIFF) tests. Experiment 2 altered the contrast levels of the faces themselves to determine whether emotion detection curves would show a pattern characteristic of magnocellular neurons and whether patients would show a deficit in performance related to early sensory processing stages. Results for experiment 1 showed that patients had impaired emotion processing and a preferential magnocellular deficit on the contrast sensitivity task. Greater deficits in ER-40 and EMODIFF performance correlated with impaired contrast sensitivity to the magnocellular-biased condition, which remained significant for the EMODIFF task even when nonspecific correlations due to group were considered in a step-wise regression. Experiment 2 showed contrast response functions indicative of magnocellular processing for both groups, with patients showing impaired performance. Impaired emotion identification on this task was also correlated with magnocellular-biased visual sensory processing dysfunction. These results provide evidence for a contribution of impaired early-stage visual processing in emotion recognition deficits in schizophrenia and suggest that a bottom-up approach to remediation may be effective. PMID:19793797

Sensory contributions to impaired emotion processing in schizophrenia.

PubMed

Butler, Pamela D; Abeles, Ilana Y; Weiskopf, Nicole G; Tambini, Arielle; Jalbrzikowski, Maria; Legatt, Michael E; Zemon, Vance; Loughead, James; Gur, Ruben C; Javitt, Daniel C

2009-11-01

Both emotion and visual processing deficits are documented in schizophrenia, and preferential magnocellular visual pathway dysfunction has been reported in several studies. This study examined the contribution to emotion-processing deficits of magnocellular and parvocellular visual pathway function, based on stimulus properties and shape of contrast response functions. Experiment 1 examined the relationship between contrast sensitivity to magnocellular- and parvocellular-biased stimuli and emotion recognition using the Penn Emotion Recognition (ER-40) and Emotion Differentiation (EMODIFF) tests. Experiment 2 altered the contrast levels of the faces themselves to determine whether emotion detection curves would show a pattern characteristic of magnocellular neurons and whether patients would show a deficit in performance related to early sensory processing stages. Results for experiment 1 showed that patients had impaired emotion processing and a preferential magnocellular deficit on the contrast sensitivity task. Greater deficits in ER-40 and EMODIFF performance correlated with impaired contrast sensitivity to the magnocellular-biased condition, which remained significant for the EMODIFF task even when nonspecific correlations due to group were considered in a step-wise regression. Experiment 2 showed contrast response functions indicative of magnocellular processing for both groups, with patients showing impaired performance. Impaired emotion identification on this task was also correlated with magnocellular-biased visual sensory processing dysfunction. These results provide evidence for a contribution of impaired early-stage visual processing in emotion recognition deficits in schizophrenia and suggest that a bottom-up approach to remediation may be effective.

The differentiation process of the I-type granitoids in southwest Japan and New South Wares in Australia

NASA Astrophysics Data System (ADS)

Kawakatsu, K.; Iwamoto, Y.; Ebisu, S.; Hasegawa, M.; Hiraiwa, N.; Kawakatsu, T.; Kitano, A.; Masuta, T.; Ootsubo, H.; Wakazono, R.

2013-12-01

Cretaceous-Paleogene Granitoids in the inner zone of southwest Japan have been divided into two series: the magnetite series that is distributed mainly in the San-in belt and the ilmenite series that is distributed mainly in San-yo belt. For 8 years, we have been investigating the two series to clear their processes of magmatic differentiation. Recently, we discovered oscillatory zoned structure, exsolution lamellae of amphibole, and relics of pyroxene left in the core of amphibole from Harima granodiorite, Nunobiki granodiorite (San-yo belt) and Daito-Yokota quartz diorite (San-in belt). The amphibole that has microstructure coexists with magnetite, ilmenite and pyrrhotite. We compared the two series for crystallization and re-equilibrium by ion substitution using the microstructure of the amphibole as 'time measure' during the differentitation process of acidic magma. While magnetites and ilmenites coexist with the core of the amphiboles, the oxygen fugacity of the San-yo belt magma was low until the later stage of magmatic differentiation where H2S from the Earth's crust mixed with it. In the subsolidus process, hydrothermal solutions circulated. On the other hand, the oxygen fugacity of the San-in belt magma began to rise in the early stage of magmatic differentiation. In the later stage, mafic magma was contaminated with SO2. The rims of amphiboles coexist with pyrrhotites in both of belts. Furthermore, the re-equilibrium of minerals underwent progressive oxidation and hydrothermal fluid circulated actively in the subsolidus process. Bingie Bingie Point at New South Wares (Eurobodalla National Park) is a peninsula about a meter around. The plutonic rocks were formed in the Devonian period and belong to the magnetite series. They are classified I-type granitoids such as those found in the inner zone of southwest Japan. They have only trace amounts of oxide minerals and pyrrhotite. The amphiboles of the granitoids have oscillatory zoned structures at pale green rims. The structures are formed by the fluid circulations of intruded granodiorite magma. The relic pyroxene is left in the core of amphibole. These minerals were crystallized under stable conditions and the microstructures were developed in the amphiboles under the subsolidus conditions. These researches contribute to clarifying magmatic differentiation and are the foundation of understanding the exchange of substances in magmatic activity.

Geologically Controlled Isotope-Time Patterns Reveal Early Differentiation and Crust Formation Processes

NASA Astrophysics Data System (ADS)

Bennett, V. C.; Nutman, A. P.

2014-12-01

The mechanisms of continental crust production and evolution in the early Earth remain controversial, as are questions of the relative roles of early differentiation versus subsequent tectonic procssing in creating Earth's chemical signatures. Here we present geologic observations integrated with whole rock major, trace element and Sm-Nd isotopic signatures and combined with U-Pb and Lu-Hf isotopic compositions of zircon populations from the same rocks, from the most extensive early rock record comprising the 3.9 Ga to 3.6 Ga terranes of southwest Greenland. These data reveal repeated patterns of formation of juvenile TTG crust and associated mafic and ultramafic rocks in convergent margin settings followed by formation of more evolved granites [1]. Our new zircon Lu-Hf data from rare 3.6-3.7 Ga tonalites within the Itsaq Gneiss Complex, obtained from single component, non-migmatitic gneisses with simple zircon populations, limited within sample Hf isotopic variability and accurate U-Pb ages, now document extraction of juvenile tonalites from a near chondritic mantle source between 3.9 Ga and 3.6 Ga. The more evolved, granitic rocks in each area show slightly negative initial ɛHf in accord with crustal reworking of the older (3.8-3.9 Ga) gniesses. There is no evidence for Hadean material in the sources of the granitoids. The Hf isotope-time patterns are consistent with juvenile crust production from a mantle source that experienced only modest amounts of prior crustal extraction. They are distinct from those predicted by reprocessing of an enriched Hadean mafic crust, as has been proposed for this region [2] and for the source of the Hadean Jack Hills zircons [3]. The well-documented, time decreasing, positive 142Nd anomalies [e.g., 4] from these rocks are further evidence of crustal derivation from a convecting mantle source, rather than reworking of an enriched mafic lithosphere. The 143Nd isotopic -time patterns are more complex, reflecting the interplay between early Sm/Nd fractionation processes as required by the 142Nd data, juvenile crustal growth and in some cases geologic disturbance of the whole rock Sm-Nd system. [1] Nutman, et al, (2013) Amer. Jour. Sci. 313, 877-911. [2] Naeraa et al.. (2012) Nature 485, 627-631. [3] Kemp et al., (2010) EPSL 296, 45-56. [4] Bennett et al., (20070 Science 318, 1907.

Notch3 and Mef2c Proteins Are Mutually Antagonistic via Mkp1 Protein and miR-1/206 MicroRNAs in Differentiating Myoblasts*

PubMed Central

Gagan, Jeffrey; Dey, Bijan K.; Layer, Ryan; Yan, Zhen; Dutta, Anindya

2012-01-01

The Notch signaling pathway is a well known regulator of skeletal muscle stem cells known as satellite cells. Loss of Notch1 signaling leads to spontaneous myogenic differentiation. Notch1, normally expressed in satellite cells, is targeted for proteasomal degradation by Numb during differentiation. A homolog of Notch1, Notch3, is also expressed in these cells but is not inhibited by Numb. We find that Notch3 is paradoxically up-regulated during the early stages of differentiation by an enhancer that requires both MyoD and activated Notch1. Notch3 itself strongly inhibits the myogenic transcription factor Mef2c, most likely by increasing the p38 phosphatase Mkp1, which inhibits the Mef2c activator p38 MAP kinase. Active Notch3 decreases differentiation. Mef2c, however, induces microRNAs miR-1 and miR-206, which directly down-regulate Notch3 and allow differentiation to proceed. Thus, the myogenic differentiation-induced microRNAs miR-1 and -206 are important for differentiation at least partly because they turn off Notch3. We suggest that the transient expression of Notch3 early in differentiation generates a temporal lag between myoblast activation by MyoD and terminal differentiation into myotubes directed by Mef2c. PMID:23055528

[Neck lymphatic metastasis, surgical methods and prognosis in early tongue squamous cell carcinoma].

PubMed

Wang, L S; Zhou, F T; Han, C B; He, X P; Zhang, Z X

2018-02-09

Objective: To investigate the different pattern of neck lymph node metastasis, the choice of surgical methods and prognosis in early tongue squamous cell carcinoma. Methods: A total of 157 patients with early oral tongue squamous cell carcinoma were included in this study. Statistical analysis was performed to identify the pattern of lymph node metastasis, to determine the best surgical procedure and to analyze the prognosis. Results: The occurrence of cervical lymph node metastasis rate was 31%(48/157). Neck lymphatic metastasis was significantly related to tumor size ( P= 0.026) and histology differentiation type ( P= 0.022). The rate of metastasis was highest in level Ⅱ [33% (16/48)]. In level Ⅳ, the incidence of lymph node metastasis was 5%(7/157), and there was no skip metastases. The possibility of level Ⅳ metastasis was higher, when level Ⅱ ( P= 0.000) or Ⅲ ( P= 0.000) involved. The differentiation tumor recurrence, neck lymphatic metastasis and adjuvant radiotherapy were prognostic factors ( P< 0.05). Multivariate analyses revealed histology differentiation type, neck lymphatic metastases and adjuvant radiotherapy were the independent prognostic factors. Conclusions: Neck lymphatic metastasis rate is high in early tongue squamous cell carcinoma, simultaneous glossectomy and neck dissection should be performed. Level Ⅳ metastasis rate is extremely low, so supraomohyoid neck dissection is sufficient for most of the time. The histology differentiation type, neck lymphatic metastasis and adjuvant radiotherapy are independent prognostic factors.

Effects of Passage Number and Differentiation Protocol on the Generation of Dopaminergic Neurons from Rat Bone Marrow-Derived Mesenchymal Stem Cells.

PubMed

Shall, Gabrielle; Menosky, Megan; Decker, Sarah; Nethala, Priya; Welchko, Ryan; Leveque, Xavier; Lu, Ming; Sandstrom, Michael; Hochgeschwender, Ute; Rossignol, Julien; Dunbar, Gary

2018-03-02

Multiple studies have demonstrated the ability of mesenchymal stem cells (MSCs) to differentiate into dopamine-producing cells, in vitro and in vivo, indicating their potential to be used in the treatment of Parkinson's disease (PD). However, there are discrepancies among studies regarding the optimal time (i.e., passage number) and method for dopaminergic induction, in vitro. In the current study, we compared the ability of early (P4) and later (P40) passaged bone marrow-derived MSCs to differentiate into dopaminergic neurons using two growth-factor-based approaches. A direct dopaminergic induction (DDI) was used to directly convert MSCs into dopaminergic neurons, and an indirect dopaminergic induction (IDI) was used to direct MSCs toward a neuronal lineage prior to terminal dopaminergic differentiation. Results indicate that both early and later passaged MSCs exhibited positive expression of neuronal and dopaminergic markers following either the DDI or IDI protocols. Additionally, both early and later passaged MSCs released dopamine and exhibited spontaneous neuronal activity following either the DDI or IDI. Still, P4 MSCs exhibited significantly higher spiking and bursting frequencies as compared to P40 MSCs. Findings from this study provide evidence that early passaged MSCs, which have undergone the DDI, are more efficient at generating dopaminergic-like cells in vitro, as compared to later passaged MSCs or MSCs that have undergone the IDI.

Utility of High Throughput Screening Techniques to Predict Stability of Monoclonal Antibody Formulations During Early Stage Development.

PubMed

Goldberg, Deborah S; Lewus, Rachael A; Esfandiary, Reza; Farkas, David C; Mody, Neil; Day, Katrina J; Mallik, Priyanka; Tracka, Malgorzata B; Sealey, Smita K; Samra, Hardeep S

2017-08-01

Selecting optimal formulation conditions for monoclonal antibodies for first time in human clinical trials is challenging due to short timelines and reliance on predictive assays to ensure product quality and adequate long-term stability. Accelerated stability studies are considered to be the gold standard for excipient screening, but they are relatively low throughput and time consuming. High throughput screening (HTS) techniques allow for large amounts of data to be collected quickly and easily, and can be used to screen solution conditions for early formulation development. The utility of using accelerated stability compared to HTS techniques (differential scanning light scattering and differential scanning fluorescence) for early formulation screening was evaluated along with the impact of excipients of various types on aggregation of monoclonal antibodies from multiple IgG subtypes. The excipient rank order using quantitative HTS measures was found to correlate with accelerated stability aggregation rate ranking for only 33% (by differential scanning fluorescence) to 42% (by differential scanning light scattering) of the antibodies tested, due to the high intrinsic stability and minimal impact of excipients on aggregation rates and HTS data. Also explored was a case study of employing a platform formulation instead of broader formulation screening for early formulation development. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Dual delivery of rhPDGF-BB and bone marrow mesenchymal stromal cells expressing the BMP2 gene enhance bone formation in a critical-sized defect model.

PubMed

Park, Shin-Young; Kim, Kyoung-Hwa; Shin, Seung-Yun; Koo, Ki-Tae; Lee, Yong-Moo; Seol, Yang-Jo

2013-11-01

Bone tissue healing is a dynamic, orchestrated process that relies on multiple growth factors and cell types. Platelet-derived growth factor-BB (PDGF-BB) is released from platelets at wound sites and induces cellular migration and proliferation necessary for bone regeneration in the early healing process. Bone morphogenetic protein-2 (BMP-2), the most potent osteogenic differentiation inducer, directs new bone formation at the sites of bone defects. This study evaluated a combinatorial treatment protocol of PDGF-BB and BMP-2 on bone healing in a critical-sized defect model. To mimic the bone tissue healing process, a dual delivery approach was designed to deliver the rhPDGF-BB protein transiently during the early healing phase, whereas BMP-2 was supplied by rat bone marrow stromal cells (BMSCs) transfected with an adenoviral vector containing the BMP2 gene (AdBMP2) for prolonged release throughout the healing process. In in vitro experiments, the dual delivery of rhPDGF-BB and BMP2 significantly enhanced cell proliferation. However, the osteogenic differentiation of BMSCs was significantly suppressed even though the amount of BMP-2 secreted by the AdBMP2-transfected BMSCs was not significantly affected by the rhPDGF-BB treatment. In addition, dual delivery inhibited the mRNA expression of BMP receptor type II and Noggin in BMSCs. In in vivo experiments, critical-sized calvarial defects in rats showed enhanced bone regeneration by dual delivery of autologous AdBMP2-transfected BMSCs and rhPDGF-BB in both the amount of new bone formed and the bone mineral density. These enhancements in bone regeneration were greater than those observed in the group treated with AdBMP2-transfected BMSCs alone. In conclusion, the dual delivery of rhPDGF-BB and AdBMP2-transfected BMSCs improved the quality of the regenerated bone, possibly due to the modulation of PDGF-BB on BMP-2-induced osteogenesis.

[Utility of early imaging of myocardial innervation scintigraphy in the diagnosis of Lewy Body Dementia].

PubMed

Camacho, V; Estorch, M; Marquié, M; Domènech, A; Flotats, A; Fernández, A; Duch, J; Geraldo, L L; Deportos, J; Artigas, C; Lleó, A; Carrió, I

2013-03-01

The importance of accurate and early diagnosis of dementia with Lewy bodies (DLB) lies in its pharmacological management. Delayed imaging of cardiac (123)I-MIBG scintigraphy allows differentiation between DLB and other neurodegenerative diseases with cognitive impairment. The aim of this study was to assess the utility of early imaging of cardiac (123)I-MIBG scintigraphy for differentiating DLB from others neurodegenerative disease with cognitive impairment. We assess retrospectively 106 patients (51 men, mean age 78 years) with cognitive impairment that underwent a cardiac (123)I-MIBG study. Planar images were acquired in anterior view of the thorax 15min (early) and 4h (delayed) after tracer administration. The heart-to-mediastinum ratios (HMR) at 15m (HMR15m) and at 4h (HMR4h) were obtained. After four years, 52 patients were diagnosed of DLB.HMR15m and HMR4h were significantly inferior in DLB respect to the others neurodegenerative diseases (1,27±0,15 vs 1,76±0,15,p<0,05) and (1,14±0,13 vs 1,68±0,19,p<0.01), respectively. The ROC analysis showed a HMR15m cut off point of 1.56 to differentiated DLB from the other dementias with a sensitivity and a specificity of 98%. Early imaging of cardiac (123)I-MIBG scintigraphy can help to differentiate DLB from other neurodegenerative diseases with cognitive impairment. Copyright © 2012 Elsevier España, S.L. y SEMNIM. All rights reserved.

Early Days for the Differentiation Policy Framework in Ontario

ERIC Educational Resources Information Center

Sianos, Helen

2017-01-01

The Ontario Ministry of Training, Colleges and Universities in Canada released "Ontario's Differentiation Policy Framework for Postsecondary Education" in 2013. This chapter examines the mandate as it pertains to the college sector.

Response terminated displays unload selective attention

PubMed Central

Roper, Zachary J. J.; Vecera, Shaun P.

2013-01-01

Perceptual load theory successfully replaced the early vs. late selection debate by appealing to adaptive control over the efficiency of selective attention. Early selection is observed unless perceptual load (p-Load) is sufficiently low to grant attentional “spill-over” to task-irrelevant stimuli. Many studies exploring load theory have used limited display durations that perhaps impose artificial limits on encoding processes. We extended the exposure duration in a classic p-Load task to alleviate temporal encoding demands that may otherwise tax mnemonic consolidation processes. If the load effect arises from perceptual demands alone, then freeing-up available mnemonic resources by extending the exposure duration should have little effect. The results of Experiment 1 falsify this prediction. We observed a reliable flanker effect under high p-Load, response-terminated displays. Next, we orthogonally manipulated exposure duration and task-relevance. Counter-intuitively, we found that the likelihood of observing the flanker effect under high p-Load resides with the duration of the task-relevant array, not the flanker itself. We propose that stimulus and encoding demands interact to produce the load effect. Our account clarifies how task parameters differentially impinge upon cognitive processes to produce attentional “spill-over” by appealing to visual short-term memory as an additional processing bottleneck when stimuli are briefly presented. PMID:24399983

Response terminated displays unload selective attention.

PubMed

Roper, Zachary J J; Vecera, Shaun P

2013-01-01

Perceptual load theory successfully replaced the early vs. late selection debate by appealing to adaptive control over the efficiency of selective attention. Early selection is observed unless perceptual load (p-Load) is sufficiently low to grant attentional "spill-over" to task-irrelevant stimuli. Many studies exploring load theory have used limited display durations that perhaps impose artificial limits on encoding processes. We extended the exposure duration in a classic p-Load task to alleviate temporal encoding demands that may otherwise tax mnemonic consolidation processes. If the load effect arises from perceptual demands alone, then freeing-up available mnemonic resources by extending the exposure duration should have little effect. The results of Experiment 1 falsify this prediction. We observed a reliable flanker effect under high p-Load, response-terminated displays. Next, we orthogonally manipulated exposure duration and task-relevance. Counter-intuitively, we found that the likelihood of observing the flanker effect under high p-Load resides with the duration of the task-relevant array, not the flanker itself. We propose that stimulus and encoding demands interact to produce the load effect. Our account clarifies how task parameters differentially impinge upon cognitive processes to produce attentional "spill-over" by appealing to visual short-term memory as an additional processing bottleneck when stimuli are briefly presented.

Early developmental influences on self-esteem trajectories from adolescence through adulthood: Impact of birth weight and motor skills.

PubMed

Poole, Kristie L; Schmidt, Louis A; Ferro, Mark A; Missiuna, Cheryl; Saigal, Saroj; Boyle, Michael H; Van Lieshout, Ryan J

2018-02-01

While the trajectory of self-esteem from adolescence to adulthood varies from person to person, little research has examined how differences in early developmental processes might affect these pathways. This study examined how early motor skill development interacted with preterm birth status to predict self-esteem from adolescence through the early 30s. We addressed this using the oldest known, prospectively followed cohort of extremely low birth weight (<1000 g) survivors (N = 179) and normal birth weight controls (N = 145) in the world, born between 1977 and 1982. Motor skills were measured using a performance-based assessment at age 8 and a retrospective self-report, and self-esteem was reported during three follow-up periods (age 12-16, age 22-26, and age 29-36). We found that birth weight status moderated the association between early motor skills and self-esteem. Stable over three decades, the self-esteem of normal birth weight participants was sensitive to early motor skills such that those with poorer motor functioning manifested lower self-esteem, while those with better motor skills manifested higher self-esteem. Conversely, differences in motor skill development did not affect the self-esteem from adolescence to adulthood in individuals born at extremely low birth weight. Early motor skill development may exert differential effects on self-esteem, depending on whether one is born at term or prematurely.

Is Serotonin Transporter Genotype Associated with Epigenetic Susceptibility or Vulnerability? Examination of the Impact of SES Risk on African American Youth

PubMed Central

Beach, S. R. H.; Brody, G. H.; Lei, M.K.; Kim, S.; Cui, J.

2014-01-01

We hypothesized that presence of the s allele in the promoter region of the serotonin transporter (5-HTTLR) would moderate the effect of early cumulative SES risk on epigenetic change among African American youth. Contrasting hypotheses regarding the shape of the interaction effect were generated using vulnerability and susceptibility frameworks and applied to data from a sample of 388 African American youth. Early, cumulative SES risk assessed at 11–13 years based on parent report interacted with presence of the s allele to predict differential methylation assessed at age 19. Across multiple tests, a differential susceptibility perspective rather than a diathesis stress framework best fit the data for genes associated with depression, consistently demonstrating greater epigenetic response to early cumulative SES risk among s allele carriers. A pattern consistent with greater impact among s allele carriers also was observed using all CpG sites across the genome that were differentially affected by early cumulative SES risk. We conclude that the s allele is associated with increased responsiveness to early cumulative SES risk among African American youth, leading to epigenetic divergence for depression-related genes in response to exposure to heightened SES risk among s allele carriers in a “for better” or “for worse” pattern. PMID:24438855

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.

Early Childhood Maltreatment and Girls' Sexual Behavior: The Mediating Role of Pubertal Timing.

PubMed

Ryan, Rebecca M; Mendle, Jane; Markowitz, Anna J

2015-09-01

Although links between early childhood maltreatment and girls' sexual behavior in adolescence have been well established, it is unclear whether different forms of maltreatment are differentially associated with sexual outcomes and whether distinct mechanisms explain associations across maltreatment types. Using data from National Longitudinal Study of Adolescent Health (Add Health), the present study examines whether physical abuse, sexual abuse, and physical neglect in early childhood differentially predict girls' age at first intercourse and number of sexual partners in early adulthood. The study also tests whether early pubertal timing mediates the link between early maltreatment and sexual behavior (N = 6,364). Findings indicate that early sexual and physical abuse were equally predictive of earlier age at first intercourse and a greater number of sexual partners, but that only the sexual abuse-age at first intercourse link was mediated by early puberty. These results suggest that sexual abuse and physical abuse are associated with earlier and riskier sexual behavior in girls relative to no maltreatment and to similar degrees. However, only the link between sexual abuse and sexual behavior involves a biological mechanism manifested in early pubertal timing. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Key science questions from the second conference on early Mars: geologic, hydrologic, and climatic evolution and the implications for life.

PubMed

Beaty, David W; Clifford, Stephen M; Borg, Lars E; Catling, David C; Craddock, Robert A; Des Marais, David J; Farmer, Jack D; Frey, Herbert V; Haberle, Robert M; McKay, Christopher P; Newsom, Horton E; Parker, Timothy J; Segura, Teresa; Tanaka, Kenneth L

2005-12-01

In October 2004, more than 130 terrestrial and planetary scientists met in Jackson Hole, WY, to discuss early Mars. The first billion years of martian geologic history is of particular interest because it is a period during which the planet was most active, after which a less dynamic period ensued that extends to the present day. The early activity left a fascinating geological record, which we are only beginning to unravel through direct observation and modeling. In considering this time period, questions outnumber answers, and one of the purposes of the meeting was to gather some of the best experts in the field to consider the current state of knowledge, ascertain which questions remain to be addressed, and identify the most promising approaches to addressing those questions. The purpose of this report is to document that discussion. Throughout the planet's first billion years, planetary-scale processes-including differentiation, hydrodynamic escape, volcanism, large impacts, erosion, and sedimentation-rapidly modified the atmosphere and crust. How did these processes operate, and what were their rates and interdependencies? The early environment was also characterized by both abundant liquid water and plentiful sources of energy, two of the most important conditions considered necessary for the origin of life. Where and when did the most habitable environments occur? Did life actually occupy them, and if so, has life persisted on Mars to the present? Our understanding of early Mars is critical to understanding how the planet we see today came to be.

Early-Life Origins of the Race Gap in Men's Mortality

ERIC Educational Resources Information Center

Warner, David F.; Hayward, Mark D.

2006-01-01

Using a life course framework, we examine the early life origins of the race gap in men's all-cause mortality. Using the National Longitudinal Survey of Older Men (1966-1990), we evaluate major social pathways by which early life conditions differentiate the mortality experiences of blacks and whites. Our findings indicate that early life…

Proceedings of the 38th Lunar and Planetary Science Conference

NASA Technical Reports Server (NTRS)

2007-01-01

The sessions in the conference include: Titan, Mars Volcanism, Mars Polar Layered Deposits, Early Solar System Isotopes, SPECIAL SESSION: Mars Reconnaissance Orbiter: New Ways of Studying the Red Planet, Achondrites: Exploring Oxygen Isotopes and Parent-Body Processes, Solar System Formation and Evolution, SPECIAL SESSION: SMART-1, . Impact Cratering: Observations and Experiments, SPECIAL SESSION: Volcanism and Tectonism on Saturnian Satellites, Solar Nebula Composition, Mars Fluvial Geomorphology, Asteroid Observations: Spectra, Mostly, Mars Sediments and Geochemistry: View from the Surface, Mars Tectonics and Crustal Dichotomy, Stardust: Wild-2 Revealed, Impact Cratering from Observations and Interpretations, Mars Sediments and Geochemistry: The Map View, Chondrules and Their Formation, Enceladus, Asteroids and Deep Impact: Structure, Dynamics, and Experiments, Mars Surface Process and Evolution, Martian Meteorites: Nakhlites, Experiments, and the Great Shergottite Age Debate, Stardust: Mainly Mineralogy, Astrobiology, Wind-Surface Interactions on Mars and Earth, Icy Satellite Surfaces, Venus, Lunar Remote Sensing, Space Weathering, and Impact Effects, Interplanetary Dust/Genesis, Mars Cratering: Counts and Catastrophes?, Chondrites: Secondary Processes, Mars Sediments and Geochemistry: Atmosphere, Soils, Brines, and Minerals, Lunar Interior and Differentiation, Mars Magnetics and Atmosphere: Core to Ionosphere, Metal-rich Chondrites, Organics in Chondrites, Lunar Impacts and Meteorites, Presolar/Solar Grains, Topics for Print Only papers are: Outer Planets/Satellites, Early Solar System, Interplanetary Dust, Comets and Kuiper Belt Objects, Asteroids and Meteoroids, Chondrites, Achondrites, Meteorite Related, Mars Reconnaissance Orbiter, Mars, Astrobiology, Planetary Differentiation, Impacts, Mercury, Lunar Samples and Modeling, Venus, Missions and Instruments, Global Warming, Education and Public Outreach, Poster sessions are: Asteroids/Kuiper Belt Objects, Galilean Satellites: Geology and Mapping, Titan, Volcanism and Tectonism on Saturnian Satellites, Early Solar System, Achondrite Hodgepodge, Ordinary Chondrites, Carbonaceous Chondrites, Impact Cratering from Observations and Interpretations, Impact Cratering from Experiments and Modeling, SMART-1, Planetary Differentiation, Mars Geology, Mars Volcanism, Mars Tectonics, Mars: Polar, Glacial, and Near-Surface Ice, Mars Valley Networks, Mars Gullies, Mars Outflow Channels, Mars Sediments and Geochemistry: Spirit and Opportunity, Mars Reconnaissance Orbiter: New Ways of Studying the Red Planet, Mars Reconnaissance Orbiter: Geology, Layers, and Landforms, Oh, My!, Mars Reconnaissance Orbiter: Viewing Mars Through Multicolored Glasses; Mars Science Laboratory, Phoenix, and ExoMars: Science, Instruments, and Landing Sites; Planetary Analogs: Chemical and Mineral, Planetary Analogs: Physical, Planetary Analogs: Operations, Future Mission Concepts, Planetary Data, Imaging, and Cartography, Outer Solar System, Presolar/Solar Grains, Stardust Mission; Interplanetary Dust, Genesis, Asteroids and Comets: Models, Dynamics, and Experiments, Venus, Mercury, Laboratory Instruments, Methods, and Techniques to Support Planetary Exploration; Instruments, Techniques, and Enabling Techologies for Planetary Exploration; Lunar Missions and Instruments, Living and Working on the Moon, Meteoroid Impacts on the Moon, Lunar Remote Sensing, Lunar Samples and Experiments, Lunar Atmosphere, Moon: Soils, Poles, and Volatiles, Lunar Topography and Geophysics, Lunar Meteorites, Chondrites: Secondary Processes, Chondrites, Martian Meteorites, Mars Cratering, Mars Surface Processes and Evolution, Mars Sediments and Geochemistry: Regolith, Spectroscopy, and Imaging, Mars Sediments and Geochemistry: Analogs and Mineralogy, Mars: Magnetics and Atmosphere, Mars Aeolian Geomorphology, Mars Data Processing and Analyses, Astrobiology, Engaging Student Educators and the Public in Planetary Science,

Role of the POZ Zinc Finger Transcription Factor FBI-1 in Human and Murine Adipogenesis

PubMed Central

Laudes, Matthias; Christodoulides, Constantinos; Sewter, Ciaran; Rochford, Justin J.; Considine, Robert V.; Sethi, Jaswinder K.; Vidal-Puig, Antonio; O’Rahilly, Stephen

2015-01-01

Poxvirus zinc finger (POZ) zinc finger domain transcription factors have been shown to play a role in the control of growth arrest and differentiation in several types of mesenchymal cells but not, as yet, adipocytes. We found that a POZ domain protein, factor that binds to inducer of short transcripts-1 (FBI-1), was induced during both murine and human preadipocyte differentiation with maximal expression levels seen at days 2–4. FBI-1 mRNA was expressed in human adipose tissue with the highest levels found in samples from morbidly obese subjects. Murine cell lines constitutively expressing FBI-1 showed evidence for accelerated adipogenesis with earlier induction of markers of differentiation and enhanced lipid accumulation, suggesting that FBI-1 may be an active participant in the differentiation process. Consistent with the properties of this family of proteins in other cell systems, 3T3L1 cells stably overexpressing FBI-1 showed reduced DNA synthesis and reduced expression of cyclin A, cyclin-dependent kinase 2, and p107, proteins known to be involved in the regulation of mitotic clonal expansion. In addition, FBI-1 reduced the transcriptional activity of the cyclin A promoter. Thus, FBI-1, a POZ zinc finger transcription factor, is induced during the early phases of human and murine preadipocyte differentiation where it may contribute to adipogenesis through influencing the switch from cellular proliferation to terminal differentiation. PMID:14701838

Visuospatial Asymmetries Arise from Differences in the Onset Time of Perceptual Evidence Accumulation.

PubMed

Newman, Daniel P; Loughnane, Gerard M; Kelly, Simon P; O'Connell, Redmond G; Bellgrove, Mark A

2017-03-22

Healthy subjects tend to exhibit a bias of visual attention whereby left hemifield stimuli are processed more quickly and accurately than stimuli appearing in the right hemifield. It has long been held that this phenomenon arises from the dominant role of the right cerebral hemisphere in regulating attention. However, methods that would enable more precise understanding of the mechanisms underpinning visuospatial bias have remained elusive. We sought to finely trace the temporal evolution of spatial biases by leveraging a novel bilateral dot motion detection paradigm. In combination with electroencephalography, this paradigm enables researchers to isolate discrete neural signals reflecting the key neural processes needed for making these detection decisions. These include signals for spatial attention, early target selection, evidence accumulation, and motor preparation. Using this method, we established that three key neural markers accounted for unique between-subject variation in visuospatial bias: hemispheric asymmetry in posterior α power measured before target onset, which is related to the distribution of preparatory attention across the visual field; asymmetry in the peak latency of the early N2c target-selection signal; and, finally, asymmetry in the onset time of the subsequent neural evidence-accumulation process with earlier onsets for left hemifield targets. Our development of a single paradigm to dissociate distinct processing components that track the temporal evolution of spatial biases not only advances our understanding of the neural mechanisms underpinning normal visuospatial attention bias, but may also in the future aid differential diagnoses in disorders of spatial attention. SIGNIFICANCE STATEMENT The significance of this research is twofold. First, it shows that individual differences in how humans direct their attention between left and right space reflects physiological differences in how early the brain starts to accumulate evidence for the existence of a visual target. Second, the novel methods developed here may have particular relevance to disorders of attention, such as unilateral spatial neglect. In the case of spatial neglect, pathological inattention to left space could have multiple underlying causes, including biased attention, impaired decision formation, or a motor deficit related to one side of space. Our development of a single paradigm to dissociate each of these components may aid in supporting more precise differential diagnosis in such heterogeneous disorders. Copyright © 2017 the authors 0270-6474/17/373378-08$15.00/0.

Rbm20-deficient cardiogenesis reveals early disruption of RNA processing and sarcomere remodeling establishing a developmental etiology for dilated cardiomyopathy.

PubMed

Beraldi, Rosanna; Li, Xing; Martinez Fernandez, Almudena; Reyes, Santiago; Secreto, Frank; Terzic, Andre; Olson, Timothy M; Nelson, Timothy J

2014-07-15

Dilated cardiomyopathy (DCM) due to mutations in RBM20, a gene encoding an RNA-binding protein, is associated with high familial penetrance, risk of progressive heart failure and sudden death. Although genetic investigations and physiological models have established the linkage of RBM20 with early-onset DCM, the underlying basis of cellular and molecular dysfunction is undetermined. Modeling human genetics using a high-throughput pluripotent stem cell platform was herein designed to pinpoint the initial transcriptome dysfunction and mechanistic corruption in disease pathogenesis. Tnnt2-pGreenZeo pluripotent stem cells were engineered to knockdown Rbm20 (shRbm20) to determine the cardiac-pathogenic phenotype during cardiac differentiation. Intracellular Ca(2+) transients revealed Rbm20-dependent alteration in Ca(2+) handling, coinciding with known pathological splice variants of Titin and Camk2d genes by Day 24 of cardiogenesis. Ultrastructural analysis demonstrated elongated and thinner sarcomeres in the absence of Rbm20 that is consistent with human cardiac biopsy samples. Furthermore, Rbm20-depleted transcriptional profiling at Day 12 identified Rbm20-dependent dysregulation with 76% of differentially expressed genes linked to known cardiac pathology ranging from primordial Nkx2.5 to mature cardiac Tnnt2 as the initial molecular aberrations. Notably, downstream consequences of Rbm20-depletion at Day 24 of differentiation demonstrated significant dysregulation of extracellular matrix components such as the anomalous overexpression of the Vtn gene. By using the pluripotent stem cell platform to model human cardiac disease according to a stage-specific cardiogenic roadmap, we established a new paradigm of familial DCM pathogenesis as a developmental disorder that is patterned during early cardiogenesis and propagated with cellular mechanisms of pathological cardiac remodeling. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Event-related delta, theta, alpha and gamma correlates to auditory oddball processing during Vipassana meditation

PubMed Central

Delorme, Arnaud; Polich, John

2013-01-01

Long-term Vipassana meditators sat in meditation vs. a control (instructed mind wandering) states for 25 min, electroencephalography (EEG) was recorded and condition order counterbalanced. For the last 4 min, a three-stimulus auditory oddball series was presented during both meditation and control periods through headphones and no task imposed. Time-frequency analysis demonstrated that meditation relative to the control condition evinced decreased evoked delta (2–4 Hz) power to distracter stimuli concomitantly with a greater event-related reduction of late (500–900 ms) alpha-1 (8–10 Hz) activity, which indexed altered dynamics of attentional engagement to distracters. Additionally, standard stimuli were associated with increased early event-related alpha phase synchrony (inter-trial coherence) and evoked theta (4–8 Hz) phase synchrony, suggesting enhanced processing of the habituated standard background stimuli. Finally, during meditation, there was a greater differential early-evoked gamma power to the different stimulus classes. Correlation analysis indicated that this effect stemmed from a meditation state-related increase in early distracter-evoked gamma power and phase synchrony specific to longer-term expert practitioners. The findings suggest that Vipassana meditation evokes a brain state of enhanced perceptual clarity and decreased automated reactivity. PMID:22648958

Interleukins 12 and 15 induce cytotoxicity and early NK-cell differentiation in type 3 innate lymphoid cells.

PubMed

Raykova, Ana; Carrega, Paolo; Lehmann, Frank M; Ivanek, Robert; Landtwing, Vanessa; Quast, Isaak; Lünemann, Jan D; Finke, Daniela; Ferlazzo, Guido; Chijioke, Obinna; Münz, Christian

2017-12-26

Type 3 innate lymphoid cells (ILC3s) fulfill protective functions at mucosal surfaces via cytokine production. Although their plasticity to become ILC1s, the innate counterparts of type 1 helper T cells, has been described previously, we report that they can differentiate into cytotoxic lymphocytes with many characteristics of early differentiated natural killer (NK) cells. This transition is promoted by the proinflammatory cytokines interleukin 12 (IL-12) and IL-15, and correlates with expression of the master transcription factor of cytotoxicity, eomesodermin (Eomes). As revealed by transcriptome analysis and flow cytometric profiling, differentiated ILC3s express CD94, NKG2A, NKG2C, CD56, and CD16 among other NK-cell receptors, and possess all components of the cytotoxic machinery. These characteristics allow them to recognize and kill leukemic cells with perforin and granzymes. Therefore, ILC3s can be harnessed for cytotoxic responses via differentiation under the influence of proinflammatory cytokines.

Spectroscopic signature of mouse embryonic stem cell-derived hepatocytes using synchrotron Fourier transform infrared microspectroscopy

NASA Astrophysics Data System (ADS)

Thumanu, Kanjana; Tanthanuch, Waraporn; Ye, Danna; Sangmalee, Anawat; Lorthongpanich, Chanchao; Parnpai, Rangsun; Heraud, Philip

2011-05-01

Stem cell-based therapy for liver regeneration has been proposed to overcome the persistent shortage in the supply of suitable donor organs. A requirement for this to succeed is to find a rapid method to detect functional hepatocytes, differentiated from embryonic stem cells. We propose Fourier transform infrared (FTIR) microspectroscopy as a versatile method to identify the early and last stages of the differentiation process leading to the formation of hepatocytes. Using synchrotron-FTIR microspectroscopy, the means of identifying hepatocytes at the single-cell level is possible and explored. Principal component analysis and subsequent partial least-squares (PLS) discriminant analysis is applied to distinguish endoderm induction from hepatic progenitor cells and matured hepatocyte-like cells. The data are well modeled by PLS with endoderm induction, hepatic progenitor cells, and mature hepatocyte-like cells able to be discriminated with very high sensitivity and specificity. This method provides a practical tool to monitor endoderm induction and has the potential to be applied for quality control of cell differentiation leading to hepatocyte formation.

Hydrogen gas treatment prolongs replicative lifespan of bone marrow multipotential stromal cells in vitro while preserving differentiation and paracrine potentials.

PubMed

Kawasaki, Haruhisa; Guan, Jianjun; Tamama, Kenichi

2010-07-02

Cell therapy with bone marrow multipotential stromal cells/mesenchymal stem cells (MSCs) represents a promising approach in the field of regenerative medicine. Low frequency of MSCs in adult bone marrow necessitates ex vivo expansion of MSCs after harvest; however, such a manipulation causes cellular senescence with loss of differentiation, proliferative, and therapeutic potentials of MSCs. Hydrogen molecules have been shown to exert organ protective effects through selective reduction of hydroxyl radicals. As oxidative stress is one of the key insults promoting cell senescence in vivo as well as in vitro, we hypothesized that hydrogen molecules prevent senescent process during MSC expansion. Addition of 3% hydrogen gas enhanced preservation of colony forming early progenitor cells within MSC preparation and prolonged the in vitro replicative lifespan of MSCs without losing differentiation potentials and paracrine capabilities. Interestingly, 3% hydrogen gas treatment did not decrease hydroxyl radical, protein carbonyl, and 8-hydroxydeoxyguanosine, suggesting that scavenging hydroxyl radical might not be responsible for these effects of hydrogen gas in this study. Copyright 2010 Elsevier Inc. All rights reserved.

Hydrogen gas treatment prolongs replicative lifespan of bone marrow multipotential stromal cells in vitro while preserving differentiation and paracrine potentials

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

Kawasaki, Haruhisa; Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210; Guan, Jianjun

2010-07-02

Cell therapy with bone marrow multipotential stromal cells/mesenchymal stem cells (MSCs) represents a promising approach in the field of regenerative medicine. Low frequency of MSCs in adult bone marrow necessitates ex vivo expansion of MSCs after harvest; however, such a manipulation causes cellular senescence with loss of differentiation, proliferative, and therapeutic potentials of MSCs. Hydrogen molecules have been shown to exert organ protective effects through selective reduction of hydroxyl radicals. As oxidative stress is one of the key insults promoting cell senescence in vivo as well as in vitro, we hypothesized that hydrogen molecules prevent senescent process during MSC expansion.more » Addition of 3% hydrogen gas enhanced preservation of colony forming early progenitor cells within MSC preparation and prolonged the in vitro replicative lifespan of MSCs without losing differentiation potentials and paracrine capabilities. Interestingly, 3% hydrogen gas treatment did not decrease hydroxyl radical, protein carbonyl, and 8-hydroxydeoxyguanosine, suggesting that scavenging hydroxyl radical might not be responsible for these effects of hydrogen gas in this study.« less

Intracellular Protein Shuttling: A Mechanism Relevant for Myelin Repair in Multiple Sclerosis?

PubMed Central

Göttle, Peter; Küry, Patrick

2015-01-01

A prominent feature of demyelinating diseases such as multiple sclerosis (MS) is the degeneration and loss of previously established functional myelin sheaths, which results in impaired signal propagation and axonal damage. However, at least in early disease stages, partial replacement of lost oligodendrocytes and thus remyelination occur as a result of resident oligodendroglial precursor cell (OPC) activation. These cells represent a widespread cell population within the adult central nervous system (CNS) that can differentiate into functional myelinating glial cells to restore axonal functions. Nevertheless, the spontaneous remyelination capacity in the adult CNS is inefficient because OPCs often fail to generate new oligodendrocytes due to the lack of stimulatory cues and the presence of inhibitory factors. Recent studies have provided evidence that regulated intracellular protein shuttling is functionally involved in oligodendroglial differentiation and remyelination activities. In this review we shed light on the role of the subcellular localization of differentiation-associated factors within oligodendroglial cells and show that regulation of intracellular localization of regulatory factors represents a crucial process to modulate oligodendroglial maturation and myelin repair in the CNS. PMID:26151843

Self-Elongation with Sequential Folding of a Filament of Bacterial Cells

NASA Astrophysics Data System (ADS)

Honda, Ryojiro; Wakita, Jun-ichi; Katori, Makoto

2015-11-01

Under hard-agar and nutrient-rich conditions, a cell of Bacillus subtilis grows as a single filament owing to the failure of cell separation after each growth and division cycle. The self-elongating filament of cells shows sequential folding processes, and multifold structures extend over an agar plate. We report that the growth process from the exponential phase to the stationary phase is well described by the time evolution of fractal dimensions of the filament configuration. We propose a method of characterizing filament configurations using a set of lengths of multifold parts of a filament. Systems of differential equations are introduced to describe the folding processes that create multifold structures in the early stage of the growth process. We show that the fitting of experimental data to the solutions of equations is excellent, and the parameters involved in our model systems are determined.

The Na+/H+ exchanger NHE6 modulates endosomal pH to control processing of amyloid precursor protein in a cell culture model of Alzheimer disease.

PubMed

Prasad, Hari; Rao, Rajini

2015-02-27

Early intervention may be key to safe and effective therapies in patients with Alzheimer disease. Endosomal dysfunction is an early step in neurodegeneration. Endosomes are a major site of production of Aβ peptide from the processing of amyloid precursor protein (APP) by clipping enzymes (β- and γ-secretases). The β-secretase enzyme BACE1 requires acidic lumen pH for optimum function, and acid pH promotes Aβ aggregation. The Na(+)/H(+) exchanger NHE6 provides a leak pathway for protons, limiting luminal acidification by proton pumps. Like APP, NHE6 expression was induced upon differentiation of SH-SY5Y neuroblastoma cells and localized to an endosomal compartment. Therefore, we investigated whether NHE6 expression altered APP localization and processing in a stably transfected cell culture model of human APP expression. We show that co-expression with NHE6 or treatment with the Na(+)/H(+) ionophore monensin shifted APP away from the trans-Golgi network into early and recycling endosomes in HEK293 cells. NHE6 alkalinized the endosomal lumen, similar to monensin, and significantly attenuated APP processing and Aβ secretion. In contrast, Aβ production was elevated upon NHE6 knockdown. We show that NHE6 transcript and protein levels are lowered in Alzheimer brains relative to control. These findings, taken together with emerging genetic evidence linking endosomal Na(+)/H(+) exchangers with Alzheimer disease, suggest that proton leak pathways may regulate Aβ generation and contribute to disease etiology. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

The Na+/H+ Exchanger NHE6 Modulates Endosomal pH to Control Processing of Amyloid Precursor Protein in a Cell Culture Model of Alzheimer Disease*

PubMed Central

Prasad, Hari; Rao, Rajini

2015-01-01

Early intervention may be key to safe and effective therapies in patients with Alzheimer disease. Endosomal dysfunction is an early step in neurodegeneration. Endosomes are a major site of production of Aβ peptide from the processing of amyloid precursor protein (APP) by clipping enzymes (β- and γ-secretases). The β-secretase enzyme BACE1 requires acidic lumen pH for optimum function, and acid pH promotes Aβ aggregation. The Na+/H+ exchanger NHE6 provides a leak pathway for protons, limiting luminal acidification by proton pumps. Like APP, NHE6 expression was induced upon differentiation of SH-SY5Y neuroblastoma cells and localized to an endosomal compartment. Therefore, we investigated whether NHE6 expression altered APP localization and processing in a stably transfected cell culture model of human APP expression. We show that co-expression with NHE6 or treatment with the Na+/H+ ionophore monensin shifted APP away from the trans-Golgi network into early and recycling endosomes in HEK293 cells. NHE6 alkalinized the endosomal lumen, similar to monensin, and significantly attenuated APP processing and Aβ secretion. In contrast, Aβ production was elevated upon NHE6 knockdown. We show that NHE6 transcript and protein levels are lowered in Alzheimer brains relative to control. These findings, taken together with emerging genetic evidence linking endosomal Na+/H+ exchangers with Alzheimer disease, suggest that proton leak pathways may regulate Aβ generation and contribute to disease etiology. PMID:25561733

Hf isotope evidence for effective impact melt homogenisation at the Sudbury impact crater, Ontario, Canada

NASA Astrophysics Data System (ADS)

Kenny, Gavin G.; Petrus, Joseph A.; Whitehouse, Martin J.; Daly, J. Stephen; Kamber, Balz S.

2017-10-01

We report on the first zircon hafnium-oxygen isotope and trace element study of a transect through one of the largest terrestrial impact melt sheets. The differentiated melt sheet at the 1.85 Ga, originally ca. 200 km in diameter Sudbury impact crater, Ontario, Canada, yields a tight range of uniform zircon Hf isotope compositions (εHf(1850) of ca. -9 to -12). This is consistent with its well-established crustal origin and indicates differentiation from a single melt that was initially efficiently homogenised. We propose that the heterogeneity in other isotopic systems, such as Pb, in early-emplaced impact melt at Sudbury is associated with volatility-related depletion during the impact cratering process. This depletion leaves the isotopic systems of more volatile elements more susceptible to contamination during post-impact assimilation of country rock, whereas the systems of more refractory elements preserve initial homogeneities. Zircon oxygen isotope compositions in the melt sheet are also restricted in range relative to those in the impacted target rocks. However, they display a marked offset approximately one-third up the melt sheet stratigraphy that is interpreted to be a result of post-impact assimilation of 18O-enirched rocks into the base of the cooling impact melt. Given that impact cratering was a more dominant process in the early history of the inner Solar System than it is today, and the possibility that impact melt sheets were sources of ex situ Hadean zircon grains, these findings may have significance for the interpretation of the early zircon Hf record. We speculate that apparent εHf-time arrays observed in the oldest terrestrial and lunar zircon datasets may be related to impact melting homogenising previously more diverse crust. We also show that spatially restricted partial melting of rocks buried beneath the superheated impact melt at Sudbury provided a zircon crystallising environment distinct to the impact melt sheet itself.

Inhibition of endogenous phosphodiesterase 7 promotes oligodendrocyte precursor differentiation and survival.

PubMed

Medina-Rodríguez, E M; Arenzana, F J; Pastor, J; Redondo, M; Palomo, V; García de Sola, R; Gil, C; Martínez, A; Bribián, A; de Castro, F

2013-09-01

During the development of the central nervous system (CNS), oligodendrocyte precursors (OPCs) are generated in specific sites within the neural tube and then migrate to colonize the entire CNS, where they differentiate into myelin-forming oligodendrocytes. Demyelinating diseases such as multiple sclerosis (MS) are characterized by the death of these cells. The CNS reacts to demyelination and by promoting spontaneous remyelination, an effect mediated by endogenous OPCs, cells that represent approximately 5-7 % of the cells in the adult brain. Numerous factors influence oligodendrogliogenesis and oligodendrocyte differentiation, including morphogens, growth factors, chemotropic molecules, extracellular matrix proteins, and intracellular cAMP levels. Here, we show that during development and in early adulthood, OPCs in the murine cerebral cortex contain phosphodiesterase-7 (PDE7) that metabolizes cAMP. We investigated the effects of different PDE7 inhibitors (the well-known BRL-50481 and two new ones, TC3.6 and VP1.15) on OPC proliferation, survival, and differentiation. While none of the PDE7 inhibitors analyzed altered OPC proliferation, TC3.6 and VP1.15 enhanced OPC survival and differentiation, processes in which ERK intracellular signaling played a key role. PDE7 expression was also observed in OPCs isolated from adult human brains and the differentiation of these OPCs into more mature oligodendroglial phenotypes was accelerated by treatment with both new PDE7 inhibitors. These findings reveal new roles for PDE7 in regulating OPC survival and differentiation during brain development and in adulthood, and they may further our understanding of myelination and facilitate the development of therapeutic remyelination strategies for the treatment of MS.

Lipidomic profiling of patient-specific iPSC-derived hepatocyte-like cells

PubMed Central

Viiri, Leena E.; Vihervaara, Terhi; Koistinen, Kaisa M.; Hilvo, Mika; Ekroos, Kim; Käkelä, Reijo; Aalto-Setälä, Katriina

2017-01-01

ABSTRACT Hepatocyte-like cells (HLCs) differentiated from human induced pluripotent stem cells (iPSCs) offer an alternative model to primary human hepatocytes to study lipid aberrations. However, the detailed lipid profile of HLCs is yet unknown. In the current study, functional HLCs were differentiated from iPSCs generated from dermal fibroblasts of three individuals by a three-step protocol through the definitive endoderm (DE) stage. In parallel, detailed lipidomic analyses as well as gene expression profiling of a set of lipid-metabolism-related genes were performed during the entire differentiation process from iPSCs to HLCs. Additionally, fatty acid (FA) composition of the cell culture media at different stages was determined. Our results show that major alterations in the molecular species of lipids occurring during DE and early hepatic differentiation stages mainly mirror the quality and quantity of the FAs supplied in culture medium at each stage. Polyunsaturated phospholipids and sphingolipids with a very long FA were produced in the cells at a later stage of differentiation. This work uncovers the previously unknown lipid composition of iPSC-HLCs and its alterations during the differentiation in conjunction with the expression of key lipid-associated genes. Together with biochemical, functional and gene expression measurements, the lipidomic analyses allowed us to improve our understanding of the concerted influence of the exogenous metabolite supply and cellular biosynthesis essential for iPSC-HLC differentiation and function. Importantly, the study describes in detail a cell model that can be applied in exploring, for example, the lipid metabolism involved in the development of fatty liver disease or atherosclerosis. PMID:28733363