Update: Exertional rhabdomyolysis, active component, U.S. Army, Navy, Air Force, and Marine Corps, 2011-2015.

PubMed

Armed Forces Health Surveillance Branch

2016-03-01

Among active component members of the U.S. Army, Navy, Air Force, and Marine Corps in 2015, there were 456 incident episodes of rhabdomyolysis likely due to physical exertion or heat stress ("exertional rhabdomyolysis"). Annual rates of incident diagnoses of exertional rhabdomyolysis increased 17% between 2014 and 2015. In 2015, the highest incidence rates occurred in service members who were male; younger than 20 years of age; black, non-Hispanic; members of the Marine Corps and Army; recruit trainees; and in combat-specific occupations. Most cases of exertional rhabdomyolysis were diagnosed at installations that support basic combat/recruit training or major ground combat units of the Army or Marine Corps. Medical care providers should consider exertional rhabdomyolysis in the differential diagnosis when service members (particularly recruits) present with muscular pain and swelling, limited range of motion, or the excretion of dark urine (e.g., myoglobinuria) after strenuous physical activity, particularly in hot, humid weather.

Notch3 expression correlates with thyroid cancer differentiation, induces apoptosis, and predicts disease prognosis.

PubMed

Somnay, Yash R; Yu, Xiao-Min; Lloyd, Ricardo V; Leverson, Glen; Aburjania, Zviadi; Jang, Samuel; Jaskula-Sztul, Renata; Chen, Herbert

2017-03-01

Thyroid tumorigenesis is characterized by a progressive loss of differentiation exhibited by a range of disease variants. The Notch receptor family (1-4) regulates developmental progression in both normal and cancerous tissues. This study sought to characterize the third Notch isoform (Notch3) across the various differentiated states of thyroid cancer, and determine its clinical impact. Notch3 expression was analyzed in a tissue microarray of normal and pathologic thyroid biopsies from 155 patients. The functional role of Notch3 was then investigated by upregulating its expression in a follicular thyroid cancer (FTC) cell line. Notch3 expression regressed across decreasingly differentiated, increasingly malignant thyroid specimens, correlated with clinicopathological attributes reflecting poor prognosis, and independently predicted survival following univariate and multivariate analyses. Overexpression of the active Notch3 intracellular domain (NICD3) in a gain-of-function FTC line led to functional activation of centromere-binding protein 1, while increasing thyroid-specific gene transcription. NICD3 induction also reduced tumor burden in vivo and initiated the intrinsic apoptotic cascade, alongside suppressing cyclin and B-cell lymphoma 2 family expression. Loss of Notch3 expression may be fundamental to the process of dedifferentiation that accompanies thyroid oncogenesis. Conversely, activation of Notch3 in thyroid cancer exerts an antiproliferative effect and restores elements of a differentiated phenotype. These findings provide preclinical rationale for evaluating Notch3 as a disease prognosticator and therapeutic target in advanced thyroid cancer. Cancer 2017;123:769-82. © 2016 American Cancer Society. © 2016 American Cancer Society.

A candidate anti-HIV reservoir compound, auranofin, exerts a selective ‘anti-memory' effect by exploiting the baseline oxidative status of lymphocytes

PubMed Central

Chirullo, B; Sgarbanti, R; Limongi, D; Shytaj, I L; Alvarez, D; Das, B; Boe, A; DaFonseca, S; Chomont, N; Liotta, L; III Petricoin, E; Norelli, S; Pelosi, E; Garaci, E; Savarino, A; Palamara, A T

2013-01-01

Central memory (TCM) and transitional memory (TTM) CD4+ T cells are known to be the major cellular reservoirs for HIV, as these cells can harbor a transcriptionally silent form of viral DNA that is not targeted by either the immune system or current antiretroviral drug regimens. In the present study, we explored the molecular bases of the anti-HIV reservoir effects of auranofin (AF), a pro-oxidant gold-based drug and a candidate compound for a cure of AIDS. We here show that TCM and TTM lymphocytes have lower baseline antioxidant defenses as compared with their naive counterpart. These differences are mirrored by the effects exerted by AF on T-lymphocytes: AF was able to exert a pro-differentiating and pro-apoptotic effect, which was more pronounced in the memory subsets. AF induced an early activation of the p38 mitogen-activated protein kinase (p38 MAPK) followed by mitochondrial depolarization and a final burst in intracellular peroxides. The pro-differentiating effect was characterized by a downregulation of the CD27 marker expression. Interestingly, AF-induced apoptosis was inhibited by pyruvate, a well-known peroxide scavenger, but pyruvate did not inhibit the pro-differentiating effect of AF, indicating that the pro-apoptotic and pro-differentiating effects involve different pathways. In conclusion, our results demonstrate that AF selectively targets the TCM/TTM lymphocyte subsets, which encompass the HIV reservoir, by affecting redox-sensitive cell death pathways. PMID:24309931

Quantification of cellular penetrative forces using lab-on-a-chip technology and finite element modeling

PubMed Central

Sanati Nezhad, Amir; Naghavi, Mahsa; Packirisamy, Muthukumaran; Bhat, Rama; Geitmann, Anja

2013-01-01

Tip-growing cells have the unique property of invading living tissues and abiotic growth matrices. To do so, they exert significant penetrative forces. In plant and fungal cells, these forces are generated by the hydrostatic turgor pressure. Using the TipChip, a microfluidic lab-on-a-chip device developed for tip-growing cells, we tested the ability to exert penetrative forces generated in pollen tubes, the fastest-growing plant cells. The tubes were guided to grow through microscopic gaps made of elastic polydimethylsiloxane material. Based on the deformation of the gaps, the force exerted by the elongating tubes to permit passage was determined using finite element methods. The data revealed that increasing mechanical impedance was met by the pollen tubes through modulation of the cell wall compliance and, thus, a change in the force acting on the obstacle. Tubes that successfully passed a narrow gap frequently burst, raising questions about the sperm discharge mechanism in the flowering plants. PMID:23630253

Osthole promotes neuronal differentiation and inhibits apoptosis via Wnt/β-catenin signaling in an Alzheimer's disease model

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

Yao, Yingjia; Gao, Zhong; Liang, Wenbo

Neurogenesis is the process by which neural stem cells (NSCs) proliferate and differentiate into neurons. This is diminished in several neurodegenerative disorders such as Alzheimer's disease (AD), which is characterized by the deposition of amyloid (A)β peptides and neuronal loss. Stimulating NSCs to replace lost neurons is therefore a promising approach for AD treatment. Our previous study demonstrated that osthole modulates NSC proliferation and differentiation, and may reduce Aβ protein expression in nerve cells. Here we investigated the mechanism underlying the effects of osthole on NSCs. We found that osthole enhances NSC proliferation and neuronal differentiation while suppressing apoptosis, effectsmore » that were exerted via activation of Wnt/β-catenin signaling. These results provide evidence that osthole can potentially be used as a therapeutic agent in the treatment of AD and other neurodegenerative disorders. - Highlights: • An Alzheimer's disease model was successfully established by transfecting APP gene into neural stem cells in vitro. • Roles of osthole in experimental AD cells were studied. • Osthole promotes proliferation and differentiation into neurons and inhibits accumulation of Aβ{sub 1–42} peptide and apoptosis. • Osthole exerts protection via Wnt/β-catenin signaling pathway.« less

Review: the role of vitamin D in nervous system health and disease.

PubMed

DeLuca, G C; Kimball, S M; Kolasinski, J; Ramagopalan, S V; Ebers, G C

2013-08-01

Vitamin D and its metabolites have pleomorphic roles in both nervous system health and disease. Animal models have been paramount in contributing to our knowledge and understanding of the consequences of vitamin D deficiency on brain development and its implications for adult psychiatric and neurological diseases. The conflation of in vitro, ex vivo, and animal model data provide compelling evidence that vitamin D has a crucial role in proliferation, differentiation, neurotrophism, neuroprotection, neurotransmission, and neuroplasticity. Vitamin D exerts its biological function not only by influencing cellular processes directly, but also by influencing gene expression through vitamin D response elements. This review highlights the epidemiological, neuropathological, experimental and molecular genetic evidence implicating vitamin D as a candidate in influencing susceptibility to a number of psychiatric and neurological diseases. The strength of evidence varies for schizophrenia, autism, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, and is especially strong for multiple sclerosis. © 2013 British Neuropathological Society.

On the nonlinear dynamics of trolling-mode AFM: Analytical solution using multiple time scales method

NASA Astrophysics Data System (ADS)

Sajjadi, Mohammadreza; Pishkenari, Hossein Nejat; Vossoughi, Gholamreza

2018-06-01

Trolling mode atomic force microscopy (TR-AFM) has resolved many imaging problems by a considerable reduction of the liquid-resonator interaction forces in liquid environments. The present study develops a nonlinear model of the meniscus force exerted to the nanoneedle of TR-AFM and presents an analytical solution to the distributed-parameter model of TR-AFM resonator utilizing multiple time scales (MTS) method. Based on the developed analytical solution, the frequency-response curves of the resonator operation in air and liquid (for different penetration length of the nanoneedle) are obtained. The closed-form analytical solution and the frequency-response curves are validated by the comparison with both the finite element solution of the main partial differential equations and the experimental observations. The effect of excitation angle of the resonator on horizontal oscillation of the probe tip and the effect of different parameters on the frequency-response of the system are investigated.

Membrane fouling in a submerged membrane bioreactor: New method and its applications in interfacial interaction quantification.

PubMed

Hong, Huachang; Cai, Xiang; Shen, Liguo; Li, Renjie; Lin, Hongjun

2017-10-01

Quantification of interfacial interactions between two rough surfaces represents one of the most pressing requirements for membrane fouling prediction and control in membrane bioreactors (MBRs). This study firstly constructed regularly rough membrane and particle surfaces by using rigorous mathematical equations. Thereafter, a new method involving surface element integration (SEI) method, differential geometry and composite Simpson's rule was proposed to quantify the interfacial interactions between the two constructed rough surfaces. This new method were then applied to investigate interfacial interactions in a MBR with the data of surface properties of membrane and foulants experimentally measured. The feasibility of the new method was verified. It was found that asperity amplitude and period of the membrane surface exerted profound effects on the total interaction. The new method had broad potential application fields especially including guiding membrane surface design for membrane fouling mitigation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tectonic analysis of folds in the Colorado plateau of Arizona

NASA Technical Reports Server (NTRS)

Davis, G. H.

1975-01-01

Structural mapping and analysis of folds in Phanerozoic rocks in northern Arizona, using LANDSAT-1 imagery, yielded information for a tectonic model useful in identifying regional fracture zones within the Colorado Plateau tectonic province. Since the monoclines within the province developed as a response to differential movements of basement blocks along high-angle faults, the monoclinal fold pattern records the position and trend of many elements of the regional fracture system. The Plateau is divided into a mosaic of complex, polyhedral crustal blocks whose steeply dipping faces correspond to major fracture zones. Zones of convergence and changes in the trend of the monoclinal traces reveal the corners of the blocks. Igneous (and salt) diapirs have been emplaced into many of the designated zones of crustal weakness. As loci of major fracturing, folding, and probably facies changes, the fractures exert control on the entrapment of oil and gas.

Platelet-Poor and Platelet-Rich Plasma Stimulate Bone Lineage Differentiation in Periodontal Ligament Stem Cells.

PubMed

Martínez, Constanza E; González, Sergio A; Palma, Verónica; Smith, Patricio C

2016-02-01

Plasma-derived fractions have been used as an autologous source of growth factors; however, limited knowledge concerning their biologic effects has hampered their clinical application. In this study, the authors analyze the content and specific effect of both platelet-rich plasma (PRP) and platelet-poor plasma (PPP) on osteoblastic differentiation using primary cultures of human periodontal ligament stem cells (HPLSCs). The authors evaluated the growth factor content of PRP and PPP using a proteome profiler array and enzyme-linked immunosorbent assay. HPLSCs were characterized by flow cytometry and differentiation assays. The effect of PRP and PPP on HPLSC bone differentiation was analyzed by quantifying calcium deposition after 14 and 21 days of treatment. Albeit at different concentrations, the two fractions had similar profiles of growth factors, the most representative being platelet-derived growth factor (PDGF) isoforms (PDGF-AA, -BB, and -AB), insulin-like growth factor binding protein (IGFBP)-2, and IGFBP-6. Both formulations exerted a comparable stimulus on osteoblastic differentiation even at low doses (2.5%), increasing calcium deposits in HPLSCs. PRP and PPP showed a similar protein profile and exerted comparable effects on bone differentiation. Further studies are needed to characterize and compare the effects of PPP and PRP on bone healing in vivo.

Sperm 1: a POU-domain gene transiently expressed immediately before meiosis I in the male germ cell.

PubMed Central

Andersen, B; Pearse, R V; Schlegel, P N; Cichon, Z; Schonemann, M D; Bardin, C W; Rosenfeld, M G

1993-01-01

Members of the POU-domain gene family encode for transcriptional regulatory molecules that are important for terminal differentiation of several organ systems, including anterior pituitary, sensory neurons, and B lymphocytes. We have identified a POU-domain factor, referred to as sperm 1 (Sprm-1). This factor is most related to the transactivator Oct-3/4, which is expressed in the early embryo, primordial germ cells, and the egg. However, in contrast with Oct-3/4, rat Sprm-1 is selectively expressed during a 36- to 48-hr period immediately preceding meiosis I in male germ cells. Although the POU-domain of Sprm-1 is divergent from the POU-domains of Oct-1 and Oct-2, random-site-selection assay reveals that Sprm-1 preferentially binds to a specific variant of the classic octamer DNA-response element in which the optimal sequence differs from that preferred by Oct-1 and Pit-1. These data suggest that the Sprm-1 gene encodes a DNA-binding protein that may exert a regulatory function in meiotic events that are required for terminal differentiation of the male germ cell. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7902581

Concurrent Schedules of Positive and Negative Reinforcement: Differential-Impact and Differential-Outcomes Hypotheses

ERIC Educational Resources Information Center

Magoon, Michael A.; Critchfield, Thomas S.

2008-01-01

Considerable evidence from outside of operant psychology suggests that aversive events exert greater influence over behavior than equal-sized positive-reinforcement events. Operant theory is largely moot on this point, and most operant research is uninformative because of a scaling problem that prevents aversive events and those based on positive…

Update: Exertional rhabdomyolysis, active component, U.S. Armed Forces, 2012-2016.

PubMed

2017-03-01

Among active component service members in 2016, there were 525 incident diagnoses of rhabdomyolysis likely due to physical exertion and/or heat stress ("exertional rhabdomyolysis"). The crude incidence rate in 2016 was 40.7 cases per 100,000 person-years. Annual rates of incident diagnoses of exertional rhabdomyolysis increased 46.2% between 2013 and 2016, with the greatest percentage change occurring between 2014 and 2015. In 2016, relative to their respective counterparts, the highest incidence rates of exertional rhabdomyolysis affected service members who were male; younger than 20 years of age; and black, non-Hispanic. During the surveillance period, annual incidence rates were highest among service members of the Marine Corps, intermediate among those in the Army, and lowest among those in the Air Force and Navy. Most cases of exertional rhabdomyolysis were diagnosed at installations that support basic combat/recruit training or major ground combat units of the Army or the Marine Corps. Medical care providers should consider exertional rhabdomyolysis in the differential diagnosis when service members (particularly recruits) present with muscular pain or swelling, limited range of motion, or the excretion of dark urine (possibly due to myoglobinuria) after strenuous physical activity, particularly in hot, humid weather.

The concerted impact of domestication and transposon insertions on methylation patterns between dogs and gray wolves

PubMed Central

Koch, Ilana Janowitz; Clark, Michelle M.; Thompson, Michael J.; Deere-Machemer, Kerry A.; Wang, Jun; Duarte, Lionel; Gnanadesikan, Gitanjali E.; McCoy, Eskender L.; Rubbi, Liudmilla; Stahler, Daniel R.; Pellegrini, Matteo; Ostrander, Elaine A.; Wayne, Robert K.; Sinsheimer, Janet S.; vonHoldt, Bridgett M.

2015-01-01

The process of domestication can exert intense trait-targeted selection on genes and regulatory regions. Specifically, rapid shifts in the structure and sequence of genomic regulatory elements could provide an explanation for the extensive, and sometimes extreme, variation in phenotypic traits observed in domesticated species. Here, we explored methylation differences from >24,000 cytosines distributed across the genomes of the domesticated dog (Canis familiaris) and the gray wolf (C. lupus). PCA and model-based cluster analyses identified two primary groups, domestic versus wild canids. A scan for significantly differentially methylated sites (DMSs) revealed species-specific patterns at 68 sites after correcting for cell heterogeneity, with weak yet significant hyper-methylation typical of purebred dogs when compared to wolves (59% and 58%, p<0.05, respectively). Additionally, methylation patterns at eight genes significantly deviated from neutrality, with similar trends of hyper-methylation in purebred dogs. The majority (>66%) of differentially methylated regions contained or were associated with repetitive elements, indicative of a genotype-mediated trend. However, DMSs were also often linked to functionally relevant genes (e.g. neurotransmitters). Finally, we utilized known genealogical relationships among Yellowstone wolves to survey transmission stability of methylation marks, from which we found a substantial fraction that demonstrated high heritability (both H2 and h2>0.99). These analyses provide a unique epigenetic insight into the molecular consequences of recent selection and radiation of our most ancient domesticated companion, the dog. These findings suggest selection has acted on methylation patterns, providing a new genomic perspective on phenotypic diversification in domesticated species. PMID:27112634

Method of fabricating an article with cavities. [with thin bottom walls

NASA Technical Reports Server (NTRS)

Dale, W. J.; Jurscaga, G. M. (Inventor)

1974-01-01

An article having a cavity with a thin bottom wall is provided by assembling a thin sheet, for example, a metal sheet, adjacent to the surface of a member having one or more apertures. A bonding adhesive is interposed between the thin sheet and the subadjacent member, and the thin sheet is subjected to a high fluid pressure. In order to prevent the differential pressure from being exerted against the thin sheet, the aperture is filled with a plug of solid material having a linear coefficient of thermal expansion higher than that of the member. When the assembly is subjected to pressure, the material is heated to a temperature such that its expansion exerts a pressure against the thin sheet thus reducing the differential pressure.

The genomic landscape shaped by selection on transposable elements across 18 mouse strains.

PubMed

Nellåker, Christoffer; Keane, Thomas M; Yalcin, Binnaz; Wong, Kim; Agam, Avigail; Belgard, T Grant; Flint, Jonathan; Adams, David J; Frankel, Wayne N; Ponting, Chris P

2012-06-15

Transposable element (TE)-derived sequence dominates the landscape of mammalian genomes and can modulate gene function by dysregulating transcription and translation. Our current knowledge of TEs in laboratory mouse strains is limited primarily to those present in the C57BL/6J reference genome, with most mouse TEs being drawn from three distinct classes, namely short interspersed nuclear elements (SINEs), long interspersed nuclear elements (LINEs) and the endogenous retrovirus (ERV) superfamily. Despite their high prevalence, the different genomic and gene properties controlling whether TEs are preferentially purged from, or are retained by, genetic drift or positive selection in mammalian genomes remain poorly defined. Using whole genome sequencing data from 13 classical laboratory and 4 wild-derived mouse inbred strains, we developed a comprehensive catalogue of 103,798 polymorphic TE variants. We employ this extensive data set to characterize TE variants across the Mus lineage, and to infer neutral and selective processes that have acted over 2 million years. Our results indicate that the majority of TE variants are introduced though the male germline and that only a minority of TE variants exert detectable changes in gene expression. However, among genes with differential expression across the strains there are twice as many TE variants identified as being putative causal variants as expected. Most TE variants that cause gene expression changes appear to be purged rapidly by purifying selection. Our findings demonstrate that past TE insertions have often been highly deleterious, and help to prioritize TE variants according to their likely contribution to gene expression or phenotype variation.

Interleukin-33/ST2 system attenuates aldosterone-induced adipogenesis and inflammation.

PubMed

Martínez-Martínez, Ernesto; Cachofeiro, Victoria; Rousseau, Elodie; Álvarez, Virginia; Calvier, Laurent; Fernández-Celis, Amaya; Leroy, Céline; Miana, María; Jurado-López, Raquel; Briones, Ana M; Jaisser, Frederic; Zannad, Faiez; Rossignol, Patrick; López-Andrés, Natalia

2015-08-15

Interleukin-33 (IL-33) but not soluble ST2 (sST2) exerts anti-inflammatory and protective effects in several tissues. Aldosterone, a proinflammatory mediator which promotes adipogenesis, is elevated in obese patients. The aim of this study was to investigate the interactions between IL-33/ST2 system and Aldosterone in adipose tissue. Rats fed a high fat diet presented increased sST2 expression, diminished IL-33/sST2 ratio and enhanced levels of differentiation and inflammation in adipose tissue as compared to controls. A similar pattern was observed in adipose tissue from C57BL/6 Aldosterone-treated mice. In both animal models, Aldosterone was correlated with sST2. Treatment of 3T3-L1 adipocytes with IL-33 delayed adipocyte differentiation diminished lipid accumulation and decreased inflammation. Aldosterone decreased IL-33 and increased sST2 expressions in differentiated adipocytes. Aldosterone-induced adipocyte differentiation and inflammation were blocked by IL-33 treatment, but sST2 did not exert any effects. The crosstalk between IL-33/ST2 and Aldosterone could be relevant in the metabolic consequences of obesity. Copyright © 2015 Elsevier Ireland Ltd. 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

Proteinuria Impairs Podocyte Regeneration by Sequestering Retinoic Acid

PubMed Central

Peired, Anna; Angelotti, Maria Lucia; Ronconi, Elisa; la Marca, Giancarlo; Mazzinghi, Benedetta; Sisti, Alessandro; Lombardi, Duccio; Giocaliere, Elisa; Della Bona, Marialuisa; Villanelli, Fabio; Parente, Eliana; Ballerini, Lara; Sagrinati, Costanza; Wanner, Nicola; Huber, Tobias B.; Liapis, Helen; Lazzeri, Elena; Lasagni, Laura

2013-01-01

In CKD, the risk of kidney failure and death depends on the severity of proteinuria, which correlates with the extent of podocyte loss and glomerular scarring. We investigated whether proteinuria contributes directly to progressive glomerulosclerosis through the suppression of podocyte regeneration and found that individual components of proteinuria exert distinct effects on renal progenitor survival and differentiation toward a podocyte lineage. In particular, albumin prevented podocyte differentiation from human renal progenitors in vitro by sequestering retinoic acid, thus impairing retinoic acid response element (RARE)-mediated transcription of podocyte-specific genes. In mice with Adriamycin nephropathy, a model of human FSGS, blocking endogenous retinoic acid synthesis increased proteinuria and exacerbated glomerulosclerosis. This effect was related to a reduction in podocyte number, as validated through genetic podocyte labeling in NPHS2.Cre;mT/mG transgenic mice. In RARE-lacZ transgenic mice, albuminuria reduced retinoic acid bioavailability and impaired RARE activation in renal progenitors, inhibiting their differentiation into podocytes. Treatment with retinoic acid restored RARE activity and induced the expression of podocyte markers in renal progenitors, decreasing proteinuria and increasing podocyte number, as demonstrated in serial biopsy specimens. These results suggest that albumin loss through the damaged filtration barrier impairs podocyte regeneration by sequestering retinoic acid and promotes the generation of FSGS lesions. Our findings may explain why reducing proteinuria delays CKD progression and provide a biologic rationale for the clinical use of pharmacologic modulators to induce regression of glomerular diseases. PMID:23949798

How deep cells feel: Mean-field Computations and Experiments

NASA Astrophysics Data System (ADS)

Buxboim, Amnon; Sen, Shamik; Discher, Dennis E.

2009-03-01

Most cells in solid tissues exert contractile forces that mechanically couple them to elastic surroundings and that significantly influence cell adhesion, cytoskeletal organization and differentiation. However, strains within the depths of matrices are often unclear and are likely relevant to thin matrices, such as basement membranes, relative to cell size as well as to defining how far cells can ``feel.'' We present experimental results for cell spreading on thin, ligand- coated gels and for prestress in stem cells in relation to gel stiffness. Matrix thickness affects cell spread area, focal adhesions and cytoskeleton organization in stem cells, which we will compare to differentiated cells. We introduce a finite element computation to estimate the elastostatic deformations within the matrix on which a cell is placed. Interfacial strains between cell and matrix show large deviations only when soft matrices are a fraction of cell dimensions, proving consistent with experiments. 3-D cell morphologies that model stem cell-derived neurons, myoblasts, and osteoblasts show that a cylinder-shaped myoblast induces the highest strains, consistent with the prominent contractility of muscle. Groups of such cells show a weak crosstalk via matrix strains only when cells are much closer than a cell-width. Cells thus feel on length scales closer to that of adhesions than on cellular scales.

Revisiting the X:A signal that specifies Caenorhabditis elegans sexual fate.

PubMed

Gladden, John M; Farboud, Behnom; Meyer, Barbara J

2007-11-01

In Caenorhabditis elegans, sex is determined by the opposing actions of X-signal elements (XSEs) and autosomal signal elements (ASEs), which communicate the ratio of X chromosomes to sets of autosomes (X:A signal). This study delves more deeply into the mechanism by which XSEs transmit X chromosome dose. We determined the relative contributions of individual XSEs to the X:A signal and showed the order of XSE strength to be sex-1 > sex-2 > fox-1 > ceh-39 >/= region 1 XSE. sex-1 exerts a more potent influence on sex determination and dosage compensation than any other XSE by functioning in two separate capacities in the pathway: sex-1 acts upstream as an XSE to repress xol-1 and downstream as an activator of hermaphrodite development and dosage compensation. Furthermore, the process of dosage compensation affects expression of the very XSEs that control it; XSEs become fully dosage compensated once sex is determined. The X:A signal is then equivalent between XO and XX animals, causing sexual differentiation to be controlled by genes downstream of xol-1 in the sex-determination pathway. Prior to the onset of dosage compensation, the difference in XSE expression between XX and XO embryos appears to be greater than twofold, making X chromosome counting a robust process.

The concerted impact of domestication and transposon insertions on methylation patterns between dogs and grey wolves.

PubMed

Janowitz Koch, Ilana; Clark, Michelle M; Thompson, Michael J; Deere-Machemer, Kerry A; Wang, Jun; Duarte, Lionel; Gnanadesikan, Gitanjali E; McCoy, Eskender L; Rubbi, Liudmilla; Stahler, Daniel R; Pellegrini, Matteo; Ostrander, Elaine A; Wayne, Robert K; Sinsheimer, Janet S; vonHoldt, Bridgett M

2016-04-01

The process of domestication can exert intense trait-targeted selection on genes and regulatory regions. Specifically, rapid shifts in the structure and sequence of genomic regulatory elements could provide an explanation for the extensive, and sometimes extreme, variation in phenotypic traits observed in domesticated species. Here, we explored methylation differences from >24 000 cytosines distributed across the genomes of the domesticated dog (Canis familiaris) and the grey wolf (Canis lupus). PCA and model-based cluster analyses identified two primary groups, domestic vs. wild canids. A scan for significantly differentially methylated sites (DMSs) revealed species-specific patterns at 68 sites after correcting for cell heterogeneity, with weak yet significant hypermethylation typical of purebred dogs when compared to wolves (59% and 58%, P < 0.05, respectively). Additionally, methylation patterns at eight genes significantly deviated from neutrality, with similar trends of hypermethylation in purebred dogs. The majority (>66%) of differentially methylated regions contained or were associated with repetitive elements, indicative of a genotype-mediated trend. However, DMSs were also often linked to functionally relevant genes (e.g. neurotransmitters). Finally, we utilized known genealogical relationships among Yellowstone wolves to survey transmission stability of methylation marks, from which we found a substantial fraction that demonstrated high heritability (both H(2) and h(2 ) > 0.99). These analyses provide a unique epigenetic insight into the molecular consequences of recent selection and radiation of our most ancient domesticated companion, the dog. These findings suggest selection has acted on methylation patterns, providing a new genomic perspective on phenotypic diversification in domesticated species. © 2015 John Wiley & Sons Ltd.

High Accumulation and In Vivo Recycling of the New Antimalarial Albitiazolium Lead to Rapid Parasite Death.

PubMed

Wein, Sharon; Taudon, Nicolas; Maynadier, Marjorie; Tran Van Ba, Christophe; Margout, Delphine; Bordat, Yann; Fraisse, Laurent; Wengelnik, Kai; Cerdan, Rachel; Bressolle-Gomeni, Françoise; Vial, Henri J

2017-08-01

Albitiazolium is the lead compound of bisthiazolium choline analogues and exerts powerful in vitro and in vivo antimalarial activities. Here we provide new insight into the fate of albitiazolium in vivo in mice and how it exerts its pharmacological activity. We show that the drug exhibits rapid and potent activity and has very favorable pharmacokinetic and pharmacodynamic properties. Pharmacokinetic studies in Plasmodium vinckei -infected mice indicated that albitiazolium rapidly and specifically accumulates to a great extent (cellular accumulation ratio, >150) in infected erythrocytes. Unexpectedly, plasma concentrations and the area under concentration-time curves increased by 15% and 69% when mice were infected at 0.9% and 8.9% parasitemia, respectively. Albitiazolium that had accumulated in infected erythrocytes and in the spleen was released into the plasma, where it was then available for another round of pharmacological activity. This recycling of the accumulated drug, after the rupture of the infected erythrocytes, likely extends its pharmacological effect. We also established a new viability assay in the P. vinckei -infected mouse model to discriminate between fast- and slow-acting antimalarials. We found that albitiazolium impaired parasite viability in less than 6 and 3 h at the ring and late stages, respectively, while parasite morphology was affected more belatedly. This highlights that viability and morphology are two parameters that can be differentially affected by a drug treatment, an element that should be taken into account when screening new antimalarial drugs. Copyright © 2017 American Society for Microbiology.

Synchrotron Radiation X-Ray Microfluorescence Reveals Polarized Distribution of Atomic Elements during Differentiation of Pluripotent Stem Cells

PubMed Central

Paulsen, Bruna S.; Rehen, Stevens K.

2011-01-01

The mechanisms underlying pluripotency and differentiation in embryonic and reprogrammed stem cells are unclear. In this work, we characterized the pluripotent state towards neural differentiated state through analysis of trace elements distribution using the Synchrotron Radiation X-ray Fluorescence Spectroscopy. Naive and neural-stimulated embryoid bodies (EB) derived from embryonic and induced pluripotent stem (ES and iPS) cells were irradiated with a spatial resolution of 20 µm to make elemental maps and qualitative chemical analyses. Results show that these embryo-like aggregates exhibit self-organization at the atomic level. Metallic elements content rises and consistent elemental polarization pattern of P and S in both mouse and human pluripotent stem cells were observed, indicating that neural differentiation and elemental polarization are strongly correlated. PMID:22195032

Guidelines For The Use, Design, And Construction Of Bridge Approach Slabs

DOT National Transportation Integrated Search

1999-11-01

Differential settlement at the roadway/bridge interface typically results in an abrupt grade change, causing driver discomfort impairing driver safety, and exerting potentially excessive impact traffic loading on the abutment. Bridge approach slabs a...

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

PubMed

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

2017-11-01

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

Evaluation of Plastic Media Blasting Equipment

DTIC Science & Technology

1987-04-01

the differential pressure across the filter element or by a timer with a differential pressure switch override. The timer and the differential pressure ...automatic. The mechanism should be activated by the differential pressure across the filter element or by a timer with a differential pressure switch override...The timer and the differential pressure switch settings should be adjustable. The dust then falls to the bottom of the baghouse for

Effect of coupling agent on durian skin fibre nanocomposite reinforced polypropylene

NASA Astrophysics Data System (ADS)

Siti Nur E'zzati, M. A.; Anuar, H.; Siti Munirah Salimah, A. R.

2018-01-01

This paper reports on the development of a composite-based natural fiber to reduce the reliance on petroleum-based product in order to amplify environmental awareness. The production of Durian Skin Nanofiber (DSNF) was conducted using biological fermentation method via rhizopus oryzae in order to obtain the nano dimension of the particle size. Polypropylene (PP) and DSNF were produced using Haake internal mixer via melt blending technique. The significant effect of maleic anhydride grafted polypropylene (MAPP) on the properties of PP/DSNF nanocomposite was investigated to study its mechanical properties which are tensile strength and thermal stability using thermogravimetric (TGA) and differential scanning analysis (DSC). The tensile property of PP nanocomposites increased from 33 MPa to 38 MPa with the presence of MAPP. The addition of MAPP also increased the thermal stability of PP/DSNF nanocomposite where the char residue increased by 52%. Besides that, the thermal degradation of PP/DSNF and PP/DSNF-MAPP were higher than PP where they exerted higher amount of weight loss at an elevated temperature. The percentage of crystallinity, %Xc, of PP nanocomposites improved with the addition of MAPP by 35% based on the differential scanning calorimetry (DSC) result. The SEM analysis showed that the PP/DSNF-MAPP exerts ductile fracture while PP/DSNF exerts brittle fracture.

Hormonal induction and antihormonal inhibition of tracheary element differentiation in Zinnia cell cultures

NASA Technical Reports Server (NTRS)

Church, D. L.; Galston, A. W.

1988-01-01

Mechanically isolated mesophyll cells of Zinnia elegans L. cv Envy differentiate to tracheary elements when cultured in inductive medium containing sufficient auxin and cytokinin. Tracheary element differentiation was induced by the three auxins (alpha-naphthaleneacetic acid, indole-3-acetic acid, and 2,4-dichlorophenoxyacetic acid) and four cytokinins (6-benzyladenine, kinetin, 2-isopentenyladenine and zeatin) tested. Tracheary element formation is inhibited or delayed if the inductive medium is supplemented with an anticytokinin, antiauxin, or inhibitor of auxin transport.

Structure and Fabrication of a Microscale Flow-Rate/Skin Friction Sensor

NASA Technical Reports Server (NTRS)

Chandrasekharan, Vijay (Inventor); Sells, Jeremy (Inventor); Sheplak, Mark (Inventor); Arnold, David P. (Inventor)

2014-01-01

A floating element shear sensor and method for fabricating the same are provided. According to an embodiment, a microelectromechanical systems (MEMS)-based capacitive floating element shear stress sensor is provided that can achieve time-resolved turbulence measurement. In one embodiment, a differential capacitive transduction scheme is used for shear stress measurement. The floating element structure for the differential capacitive transduction scheme incorporates inter digitated comb fingers forming differential capacitors, which provide electrical output proportional to the floating element deflection.

Effect of diosgenin on metabolic dysfunction: Role of ERβ in the regulation of PPARγ

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

Wang, Xin, E-mail: xinwang@fmmu.edu.cn; Liu, Jun; Long, Zi

The present study was designed to investigate the effect of diosgenin (DSG) on metabolic dysfunction and to elucidate the possible molecular mechanisms. High fat (HF) diet-fed mice and 3T3-L1 preadipocytes was used to evaluate the effect of DSG. We showed that DSG attenuated metabolic dysfunction in HF diet-fed mice, as evidenced by reduction of blood glucose level and improvement of glucose and insulin intolerance. DSG ameliorated oxidative stress, reduced body weight, fat pads, and systematic lipid profiles and attenuated lipid accumulation. DSG inhibited 3T3-L1 adipocyte differentiation and reduced adipocyte size through regulating key factors. DSG inhibited PPARγ and its targetmore » gene expression both in differentiated 3T3-L1 adipocytes and fat tissues in HF diet-fed mice. Overexpression of PPARγ suppressed DSG-inhibited adipocyte differentiation. DSG significantly increased nuclear expression of ERβ. Inhibition of ERβ significantly suppressed DSG-exerted suppression of adipocyte differentiation and PPARγ expression. In response to DSG stimulation, ERβ bound with RXRα and dissociated RXRα from PPARγ, leading to the reduction of transcriptional activity of PPARγ. These data provide new insight into the mechanisms underlying the inhibitory effect of DSG on adipocyte differentiation and demonstrate that ERβ-exerted regulation of PPARγ expression and activity is critical for DSG-inhibited adipocyte differentiation. - Highlights: • Diosgenin (DSG) attenuated metabolic dysfunction in high fat (HF) diet-fed mice. • DSG reduced oxidative stress and lipid accumulation in HF diet-fed mice. • DSG inhibited 3T3-L1 adipocyte differentiation and reduced adipocyte size. • DSG induced the binding of ERβ with RXRα. • DSG-induced activation of ERβ dissociated RXRα from PPARγ and reduced PPARγ activity.« less

Whole blood gene expression in adolescent chronic fatigue syndrome: an exploratory cross-sectional study suggesting altered B cell differentiation and survival.

PubMed

Nguyen, Chinh Bkrong; Alsøe, Lene; Lindvall, Jessica M; Sulheim, Dag; Fagermoen, Even; Winger, Anette; Kaarbø, Mari; Nilsen, Hilde; Wyller, Vegard Bruun

2017-05-11

Chronic fatigue syndrome (CFS) is a prevalent and disabling condition affecting adolescents. The pathophysiology is poorly understood, but immune alterations might be an important component. This study compared whole blood gene expression in adolescent CFS patients and healthy controls, and explored associations between gene expression and neuroendocrine markers, immune markers and clinical markers within the CFS group. CFS patients (12-18 years old) were recruited nation-wide to a single referral center as part of the NorCAPITAL project. A broad case definition of CFS was applied, requiring 3 months of unexplained, disabling chronic/relapsing fatigue of new onset, whereas no accompanying symptoms were necessary. Healthy controls having comparable distribution of gender and age were recruited from local schools. Whole blood samples were subjected to RNA sequencing. Immune markers were blood leukocyte counts, plasma cytokines, serum C-reactive protein and immunoglobulins. Neuroendocrine markers encompassed plasma and urine levels of catecholamines and cortisol, as well as heart rate variability indices. Clinical markers consisted of questionnaire scores for symptoms of post-exertional malaise, inflammation, fatigue, depression and trait anxiety, as well as activity recordings. A total of 29 CFS patients and 18 healthy controls were included. We identified 176 genes as differentially expressed in patients compared to controls, adjusting for age and gender factors. Gene set enrichment analyses suggested impairment of B cell differentiation and survival, as well as enhancement of innate antiviral responses and inflammation in the CFS group. A pattern of co-expression could be identified, and this pattern, as well as single gene transcripts, was significantly associated with indices of autonomic nervous activity, plasma cortisol, and blood monocyte and eosinophil counts. Also, an association with symptoms of post-exertional malaise was demonstrated. Adolescent CFS is characterized by differential gene expression pattern in whole blood suggestive of impaired B cell differentiation and survival, and enhanced innate antiviral responses and inflammation. This expression pattern is associated with neuroendocrine markers of altered HPA axis and autonomic nervous activity, and with symptoms of post-exertional malaise. Trial registration Clinical Trials NCT01040429.

Finite Element Modeling of Intermuscular Interactions and Myofascial Force Transmission

DTIC Science & Technology

2001-10-25

obtained explain force differences at the distal and proximal tendons of muscles that have mechanical interaction. This is in agreement with experimental...consequence is that active force generated within one muscle may be exerted at the tendon of another muscle. Keywords- Finite element method...7]. Therefore, in vivo there is an additional route for force transmission out off the muscle, which completely bypasses the tendon of the muscle

Small drill-hole, gas mini-permeameter probe

DOEpatents

Molz, III, Fred J.; Murdoch, Lawrence C.; Dinwiddie, Cynthia L.; Castle, James W.

2002-12-03

The distal end of a basic tube element including a stopper device with an expandable plug is positioned in a pre-drilled hole in a rock face. Rotating a force control wheel threaded on the tube element exerts force on a sleeve that in turn causes the plug component of the stopper means to expand and seal the distal end of the tube in the hole. Gas under known pressure is introduced through the tube element. A thin capillary tube positioned in the tube element connects the distal end of the tube element to means to detect and display pressure changes and data that allow the permeability of the rock to be determined.

Small drill-hole, gas mini-permeameter probe

DOEpatents

Molz, III, Fred J.; Murdoch, Lawrence C.; Dinwiddie, Cynthia L.; Castle, James W.

2002-01-01

The distal end of a basic tube element including a stopper device with an expandable plug is positioned in a pre-drilled hole in a rock face. Rotating a force control wheel threaded on the tube element exerts force on a sleeve that in turn causes the plug component of the stopper means to expand and seal the distal end of the tube in the hole. Gas under known pressure is introduced through the tube element. A thin capillary tube positioned in the tube element connects the distal end of the tube element to means to detect and display pressure changes and data that allow the permeability of the rock to be determined.

Asynchronous oscillations of two zebrafish CLOCK partners reveal differential clock control and function

PubMed Central

Cermakian, Nicolas; Whitmore, David; Foulkes, Nicholas S.; Sassone-Corsi, Paolo

2000-01-01

Most clock genes encode transcription factors that interact to elicit cooperative control of clock function. Using a two-hybrid system approach, we have isolated two different partners of zebrafish (zf) CLOCK, which are similar to the mammalian BMAL1 (brain and muscle arylhydrocarbon receptor nuclear translocator-like protein 1). The two homologs, zfBMAL1 and zfBMAL2, contain conserved basic helix–loop–helix-PAS (Period-Arylhydrocarbon receptor-Singleminded) domains but diverge in the carboxyl termini, thus bearing different transcriptional activation potential. As for zfClock, the expression of both zfBmals oscillates in most tissues in the animal. However, in many tissues, the peak, levels, and kinetics of expression are different between the two genes and for the same gene from tissue to tissue. These results support the existence of independent peripheral oscillators and suggest that zfBMAL1 and zfBMAL2 may exert distinct circadian functions, interacting differentially with zfCLOCK at various times in different tissues. Our findings also indicate that multiple controls may be exerted by the central clock and/or that peripheral oscillators can differentially interpret central clock signals. PMID:10760301

Athletes' leg pains.

PubMed Central

Orava, S.; Puranen, J.

1979-01-01

The frequency and nature of exertion pains of the leg in athletes were studied in 2,750 cases of overuse injuries treated at the Sports Clinic of the Deaconess Institute of Oulu, Finland, during the years 1972-1977. 465 cases of exertion pain (18%) were located in the shin. The medial tibial syndrome was the most common overuse injury among these athletes, comprising 9.5% of all exertion injuries and 60% of the leg exertion pains. Together with stress fracture of the tibia, the second most common exertion pain of the leg, it accounted for 75% of the total leg pains. There are certain difficulties in differentiating between the medial tibial syndrome and stress fracture of the tibia. They both occur at the same site with similar symptoms. Radiological examination and isotope scanning are needed. The medial tibial syndrome is an overuse injury at the medial tibial border caused by running exercises. The pain is elicited by exertional ischaemia. The pathogenesis is explained by increased pressure in the fascial compartment of the deep flexor muscles due to prolonged exercise. Similar chronic ischaemic pains from exercise are also found in other fascial compartments of the leg, especially in the anterior compartment. The only treatment needed for stress fractures is rest from training. Fascial compartment pains also usually subside. If chronic fascial syndromes prevent training, fasciotomy is recommended as a reliable method to restore the athlete to normal training without pains. PMID:486888

Copper systematics during mantle melting and crustal differentiation in arcs: implications for S and Pb budgets of the continental crust

NASA Astrophysics Data System (ADS)

Lee, C.; Chin, E. J.; Dasgupta, R.; Luffi, P. I.; Le Roux, V.

2010-12-01

During mid-ocean ridge melting, Cu behaves like Sc and is therefore moderately incompatible, as evidenced by the twofold increase in Cu content in MORBs compared to the mantle. However, Cu content in the continental crust is comparable to that of the mantle, implying that during continental crust formation, Cu becomes effectively compatible. Cu is one of the only elements that exhibits Jekyll and Hyde behavior. This switch to being compatible is consistent with the observation that for the majority of arc magmas (as well as MORBs), Cu decreases with increasing SiO2 and decreasing MgO. Using natural samples, we infer new partition coefficients that indicate Cu is incompatible in olivine, pyroxenes, amphiboles, and biotite. The only mineral to exert significant control on Cu partitioning is sulfide. Cu behaves incompatibly during mantle melting because the modal abundance of sulfides relative to silicate minerals is extremely low. The monotonic decrease in Cu in most differentiating arc magmas requires sulfide saturation. In addition, the similar abundances of Cu in many primitive arc magmas compared to MORBs suggests that mantle melting in both environments occurs not only at sulfide saturation but without the need for excess Cu (or S). In a few cases, however, primitive arc magmas begin with high Cu or show increases in Cu with differentiation, which most likely requires unusually high oxygen fugacities in the source or magmatic evolution towards high oxygen fugacity. Such cases may be important for the origin of Cu porphyry deposits, but are generally rare. Because of the close link between Cu and sulfide during magma differentiation, Cu can be used as a proxy for the pre-degassed S content of arc magmas. The S content of continental crust, like many volatile elements, is basically unconstrained, but it can be inferred from Cu, which is much better constrained. Finally, the fact that the continental crust is highly depleted in Cu implies that there is a missing reservoir rich in Cu and by necessity sulfide. Cumulate xenoliths in arc settings fit this persona. Delamination of these cumulates, embedded with sulfides, will have profound implications for the Pb isotopic evolution of the mantle by linking the Pb paradox to continent formation.

The reverse transcriptase encoded by LINE-1 retrotransposons in the genesis, progression and therapy of cancer

NASA Astrophysics Data System (ADS)

Sciamanna, Ilaria; De Luca, Chiara; Spadafora, Corrado

2016-02-01

In higher eukaryotic genomes, Long Interspersed Nuclear Element 1 (LINE-1) retrotransposons represent a large family of repeated genomic elements. They transpose using a reverse transcriptase (RT), which they encode as part of the ORF2p product. RT inhibition in cancer cells, either via RNA interference-dependent silencing of active LINE-1 elements, or using RT inhibitory drugs, reduces cancer cell proliferation, promotes their differentiation and antagonizes tumor progression in animal models. Indeed, the nonnucleoside RT inhibitor efavirenz has recently been tested in a phase II clinical trial with metastatic prostate cancer patients. An in-depth analysis of ORF2p in a mouse model of breast cancer showed ORF2p to be precociously expressed in precancerous lesions and highly abundant in advanced cancer stages, while being barely detectable in normal breast tissue, providing a rationale for the finding that RT-expressing tumours are therapeutically sensitive to RT inhibitors. We summarise mechanistic and gene profiling studies indicating that highly abundant LINE-1-derived RT can “sequester” RNA substrates for reverse transcription in tumor cells, entailing the formation of RNA:DNA hybrid molecules and impairing the overall production of regulatory miRNAs, with a global impact on the cell transcriptome. Based on these data, LINE-1-ORF2 encoded RT has a tumor-promoting potential that is exerted at an epigenetic level. We propose a model whereby LINE1-RT drives a previously unrecognized global regulatory process, the deregulation of which drives cell transformation and tumorigenesis and possibly implicated in cancer cell heterogeneity.

Ghosts: Gateway to Organizational Transformation.

ERIC Educational Resources Information Center

Weitzel, Tim; Had, Gary

2001-01-01

"Ghosts" are elements that influence an organization's view of itself, its ways of working, and its culturally specific attitudes; they exert an indirect influence over everything that happens within an organization. Successful organizational change requires identifying and integrating these ghosts. (JOW)

Hermeneutics of differential calculus in eighteenth-century northern Germany.

PubMed

Blanco, Mónica

2008-01-01

This paper applies comparative textbook analysis to studying the mathematical development of differential calculus in northern German states during the eighteenth century. It begins with describing how the four textbooks analyzed presented the foundations of calculus and continues with assessing the influence each of these foundational approaches exerted on the resolution of problems, such as the determination of tangents and extreme values, and even on the choice of coordinates for both algebraic and transcendental curves.

Differential prooxidative effects of the green tea polyphenol, (-)-epigallocatechin-3-gallate, in normal and oral cancer cells are related to differences in sirtuin 3 signaling.

PubMed

Tao, Ling; Park, Jong-Yung; Lambert, Joshua D

2015-02-01

We have previously reported that the green tea catechin, (-)-epigallocatechin-3-gallate (EGCG), can induce oxidative stress in oral cancer cells but exerts antioxidant effects in normal cells. Here, we report that these differential prooxidative effects are associated with sirtuin 3 (SIRT3), an important mitochondrial redox modulator. EGCG rapidly induced mitochondria-localized reactive oxygen species in human oral squamous carcinoma cells (SCC-25, SCC-9) and premalignant leukoplakia cells (MSK-Leuk1), but not in normal human gingival fibroblast cells (HGF-1). EGCG suppressed SIRT3 mRNA and protein expression, as well as, SIRT3 activity in SCC-25 cells, whereas it increased SIRT3 activity in HGF-1 cells. EGCG selectively decreased the nuclear localization of the estrogen-related receptor α (ERRα), the transcription factor regulating SIRT3 expression, in SCC-25 cells. This indicates that EGCG may regulate SIRT3 transcription in oral cancer cells via ERRα. EGCG also differentially modulated the mRNA expressions of SIRT3-associated downstream targets including glutathione peroxidase 1 and superoxide dismutase 2 in normal and oral cancer cells. SIRT3 represents a novel potential target through which EGCG exerts differential prooxidant effects in cancer and normal cells. Our results provide new biomarkers to be further explored in animal studies. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Temperature differential detection device

DOEpatents

Girling, P.M.

1986-04-22

A temperature differential detection device for detecting the temperature differential between predetermined portions of a container wall is disclosed as comprising a Wheatstone bridge circuit for detecting resistance imbalance with a first circuit branch having a first elongated wire element mounted in thermal contact with a predetermined portion of the container wall, a second circuit branch having a second elongated wire element mounted in thermal contact with a second predetermined portion of a container wall with the wire elements having a predetermined temperature-resistant coefficient, an indicator interconnected between the first and second branches remote from the container wall for detecting and indicating resistance imbalance between the first and second wire elements, and connector leads for electrically connecting the wire elements to the remote indicator in order to maintain the respective resistance value relationship between the first and second wire elements. The indicator is calibrated to indicate the detected resistance imbalance in terms of a temperature differential between the first and second wall portions. 2 figs.

Temperature differential detection device

DOEpatents

Girling, Peter M.

1986-01-01

A temperature differential detection device for detecting the temperature differential between predetermined portions of a container wall is disclosed as comprising a Wheatstone bridge circuit for detecting resistance imbalance with a first circuit branch having a first elongated wire element mounted in thermal contact with a predetermined portion of the container wall, a second circuit branch having a second elongated wire element mounted in thermal contact with a second predetermined portion of a container wall with the wire elements having a predetermined temperature-resistant coefficient, an indicator interconnected between the first and second branches remote from the container wall for detecting and indicating resistance imbalance between the first and second wire elements, and connector leads for electrically connecting the wire elements to the remote indicator in order to maintain the respective resistance value relationship between the first and second wire elements. The indicator is calibrated to indicate the detected resistance imbalance in terms of a temperature differential between the first and second wall portions.

Nonconsumptive predator-driven mortality causes natural selection on prey.

PubMed

Siepielski, Adam M; Wang, Jason; Prince, Garrett

2014-03-01

Predators frequently exert natural selection through differential consumption of their prey. However, predators may also cause prey mortality through nonconsumptive effects, which could cause selection if different prey phenotypes are differentially susceptible to this nonconsumptive mortality. Here we present an experimental test of this hypothesis, which reveals that nonconsumptive mortality imposed by predatory dragonflies causes selection on their damselfly prey favoring increased activity levels. These results are consistent with other studies of predator-driven selection, however, they reveal that consumption alone is not the only mechanism by which predators can exert selection on prey. Uncovering this mechanism also suggests that prey defensive traits may represent adaptations to not only avoid being consumed, but also for dealing with other sources of mortality caused by predators. Demonstrating selection through both consumptive and nonconsumptive predator mortality provides us with insight into the diverse effects of predators as an evolutionary force. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

Changes in the selection differential exerted on a marine snail during the ontogeny of a predatory shore crab.

PubMed

Pakes, D; Boulding, E G

2010-08-01

Empirical estimates of selection gradients caused by predators are common, yet no one has quantified how these estimates vary with predator ontogeny. We used logistic regression to investigate how selection on gastropod shell thickness changed with predator size. Only small and medium purple shore crabs (Hemigrapsus nudus) exerted a linear selection gradient for increased shell-thickness within a single population of the intertidal snail (Littorina subrotundata). The shape of the fitness function for shell thickness was confirmed to be linear for small and medium crabs but was humped for large male crabs, suggesting no directional selection. A second experiment using two prey species to amplify shell thickness differences established that the selection differential on adult snails decreased linearly as crab size increased. We observed differences in size distribution and sex ratios among three natural shore crab populations that may cause spatial and temporal variation in predator-mediated selection on local snail populations.

Combination of miRNA499 and miRNA133 Exerts a Synergic Effect on Cardiac Differentiation

PubMed Central

Pisano, Federica; Altomare, Claudia; Cervio, Elisabetta; Barile, Lucio; Rocchetti, Marcella; Ciuffreda, Maria Chiara; Malpasso, Giuseppe; Copes, Francesco; Mura, Manuela; Danieli, Patrizia; Viarengo, Gianluca; Zaza, Antonio; Gnecchi, Massimiliano

2015-01-01

Several studies have demonstrated that miRNA are involved in cardiac development, stem cell maintenance, and differentiation. In particular, it has been shown that miRNA133, miRNA1, and miRNA499 are involved in progenitor cell differentiation into cardiomyocytes. However, it is unknown whether different miRNA may act synergistically to improve cardiac differentiation. We used mouse P19 cells as a cardiogenic differentiation model. miRNA499, miRNA1, or miRNA133 were transiently over-expressed in P19 cells individually or in different combinations. The over-expression of miRNA499 alone increased the number of beating cells and the association of miRNA499 with miRNA133 exerted a synergistic effect, further increasing the number of beating cells. Real-time polymerase chain reaction showed that the combination of miRNA499 + 133 enhanced the expression of cardiac genes compared with controls. Western blot and immunocytochemistry for connexin43 and cardiac troponin T confirmed these findings. Importantly, caffeine responsiveness, a clear functional parameter of cardiac differentiation, was increased by miRNA499 in association with miRNA133 and was directly correlated with the activation of the cardiac troponin I isoform promoter. Cyclic contractions were reversibly abolished by extracellular calcium depletion, nifedipine, ryanodine, and IP3R blockade. Finally, we demonstrated that the use of miRNA499 + 133 induced cardiac differentiation even in the absence of dimethyl sulfoxide. Our results show that the areas spontaneously contracting possess electrophysiological and pharmacological characteristics compatible with true cardiac excitation-contraction coupling. The translational relevance of our findings was reinforced by the demonstration that the over-expression of miRNA499 and miRNA133 was also able to induce the differentiation of human mesenchymal stromal cells toward the cardiac lineage. Stem Cells 2015;33:1187–1199 PMID:25534971

Bradykinin mediates myogenic differentiation in murine myoblasts through the involvement of SK1/Spns2/S1P2 axis.

PubMed

Bruno, Gennaro; Cencetti, Francesca; Bernacchioni, Caterina; Donati, Chiara; Blankenbach, Kira Vanessa; Thomas, Dominique; Meyer Zu Heringdorf, Dagmar; Bruni, Paola

2018-05-01

Skeletal muscle tissue retains a remarkable regenerative capacity due to the activation of resident stem cells that in pathological conditions or after tissue damage proliferate and commit themselves into myoblasts. These immature myogenic cells undergo differentiation to generate new myofibers or repair the injured ones, giving a strong contribution to muscle regeneration. Cytokines and growth factors, potently released after tissue injury by leukocytes and macrophages, are not only responsible of the induction of the initial inflammatory response, but can also affect skeletal muscle regeneration. Growth factors exploit sphingosine kinase (SK), the enzyme that catalyzes the production of sphingosine 1-phosphate (S1P), to exert their biological effects in skeletal muscle. In this paper we show for the first time that bradykinin (BK), the leading member of kinin/kallikrein system, is able to induce myogenic differentiation in C2C12 myoblasts. Moreover, evidence is provided that SK1, the specific S1P-transporter spinster homolog 2 (Spns2) and S1P 2 receptor are involved in the action exerted by BK, since pharmacological inhibition/antagonism or specific down-regulation significantly alter BK-induced myogenic differentiation. Moreover, the molecular mechanism initiated by BK involves a rapid translocation of SK1 to plasma membrane, analyzed by time-lapse immunofluorescence analysis. The present study highlights the role of SK1/Spns2/S1P receptor 2 signaling axis in BK-induced myogenic differentiation, thus confirming the crucial involvement of this pathway in skeletal muscle cell biology. Copyright © 2018 Elsevier Inc. All rights reserved.

microRNA regulation of T-cell differentiation and function

PubMed Central

Jeker, Lukas T.; Bluestone, Jeffrey A.

2013-01-01

Summary microRNAs (miRNAs) are emerging as key controllers of T-cell differentiation and function. Their expression is dynamically regulated by extracellular signals such as costimulation and cytokine signals. miRNAs set thresholds for gene expression and optimize protein concentrations of genetic networks. Absence of individual miRNAs can lead to severe immune dysfunction. Here we review emerging principles and provide examples of important functions exerted by miRNAs. Although our understanding of miRNA function in T-cell differentiation is still rudimentary, the available evidence leaves no doubt that these small posttranscriptional regulators are indispensable for proper functioning of the immune system. PMID:23550639

Loaded transducer for downhole drilling components

DOEpatents

Hall, David R [Provo, UT; Fox, Joe [Spanish Fork, UT; Daly, Jeffery E [Cypress, TX

2009-05-05

A system for transmitting information between downhole components has a first downhole component with a first mating surface and a second downhole component having a second mating surface configured to substantially mate with the first mating surface. The system also has a first transmission element with a first communicating surface and is mounted within a recess in the first mating surface. The first transmission element also has an angled surface. The recess has a side with multiple slopes for interacting with the angled surface, each slope exerting a different spring force on the first transmission element. A second transmission element has a second communicating surface mounted proximate the second mating surface and adapted to communicate with the first communicating surface.

Influence of ambient music on perceived exertion during a pulmonary rehabilitation session: a randomized crossover study.

PubMed

Reychler, Gregory; Mottart, Florian; Boland, Maelle; Wasterlain, Emmanuelle; Pieters, Thierry; Caty, Gilles; Liistro, Giuseppe

2015-05-01

Pulmonary rehabilitation is a key element in the treatment of COPD. Music has been shown to have a positive effect on parameters related to a decrease in exercise tolerance. The aim of this study was to evaluate the effect of listening to ambient music on perceived exertion during a pulmonary rehabilitation session for COPD subjects. COPD subjects randomly performed a session of pulmonary rehabilitation with or without ambient music. Perceived exertion (Borg scales), anxiety (Hospital Anxiety and Depression Scale-Anxiety Subscale), dyspnea (visual analog scale), and cardiorespiratory parameters were compared at the end of both sessions. Forty-one subjects were analyzed. The characteristics of the COPD subjects were as follows: age, 70.5 ± 8.4 y; body mass index, 22.7 ± 3.9 kg/m(2); and FEV1, 38.6 ± 12.5 % predicted. Perceived exertion was not modified by ambient music, but anxiety was improved (P = .02). Dyspnea, fatigue and cardiorespiratory parameters were not influenced by music during a typical session of the pulmonary rehabilitation program. This study demonstrates that perceived exertion during one pulmonary rehabilitation session was not influenced by ambient music. However, a positive effect on anxiety was observed. (ClinicalTrials.gov registration NCT01833260.). Copyright © 2015 by Daedalus Enterprises.

Trace elements as quantitative probes of differentiation processes in planetary interiors

NASA Technical Reports Server (NTRS)

Drake, M. J.

1980-01-01

The characteristic trace element signature that each mineral in the source region imparts on the magma constitutes the conceptual basis for trace element modeling. It is shown that abundances of trace elements in extrusive igneous rocks may be used as petrological and geochemical probes of the source regions of the rocks if differentiation processes, partition coefficients, phase equilibria, and initial concentrations in the source region are known. Although compatible and incompatible trace elements are useful in modeling, the present review focuses primarily on examples involving the rare-earth elements.

Pressure deformation of tires using differential stiffness for triangular solid-of-revolution elements

NASA Technical Reports Server (NTRS)

Chen, C. H. S.

1975-01-01

The derivation is presented of the differential stiffness for triangular solid of revolution elements. The derivation takes into account the element rigid body rotation only, the rotation being about the circumferential axis. Internal pressurization of a pneumatic tire is used to illustrate the application of this feature.

Bexarotene via CBP/p300 induces suppression of NF-κB-dependent cell growth and invasion in thyroid cancer.

PubMed

Cras, Audrey; Politis, Béatrice; Balitrand, Nicole; Darsin-Bettinger, Diane; Boelle, Pierre Yves; Cassinat, Bruno; Toubert, Marie-Elisabeth; Chomienne, Christine

2012-01-15

Retinoic acid (RA) treatment has been used for redifferentiation of metastatic thyroid cancer with loss of radioiodine uptake. The aim of this study was to improve the understanding of RA resistance and investigate the role of bexarotene in thyroid cancer cells. A model of thyroid cancer cell lines with differential response to RA was used to evaluate the biological effects of retinoid and rexinoid and to correlate this with RA receptor levels. Subsequently, thyroid cancer patients were treated with 13-cis RA and bexarotene and response evaluated on radioiodine uptake reinduction on posttherapy scan and conventional imaging. In thyroid cancer patients, 13-cis RA resistance can be bypassed in some tumors by bexarotene. A decreased tumor growth without differentiation was observed confirming our in vitro data. Indeed, we show that ligands of RARs or RXRs exert different effects in thyroid cancer cell lines through either differentiation or inhibition of cell growth and invasion. These effects are associated with restoration of RARβ and RXRγ levels and downregulation of NF-κB targets genes. We show that bexarotene inhibits the transactivation potential of NF-κB in an RXR-dependent manner through decreased promoter permissiveness without interfering with NF-κB nuclear translocation and binding to its responsive elements. Inhibition of transcription results from the release of p300 coactivator from NF-κB target gene promoters and subsequent histone deacetylation. This study highlights dual mechanisms by which retinoids and rexinoids may target cell tumorigenicity, not only via RARs and RXRs, as expected, but also via NF-κB pathway. ©2011 AACR.

Branding a State University: Doing It Right

ERIC Educational Resources Information Center

Dholakia, Ruby Roy; Acciardo, Linda A.

2014-01-01

Shrinking financial support from governments and forecast declines in the college-going population have combined to exert tremendous pressure on institutions of higher learning. Branding as a strategy has become more popular as a way of differentiating an institution from its competition, but the complexity of higher education makes branding an…

Joining mechanism with stem tension and interlocked compression ring

DOEpatents

James, Allister W.; Morrison, Jay A.

2012-09-04

A stem (34) extends from a second part (30) through a hole (28) in a first part (22). A groove (38) around the stem provides a non-threaded contact surface (42) for a ring element (44) around the stem. The ring element exerts an inward force against the non-threaded contact surface at an angle that creates axial tension (T) in the stem, pulling the second part against the first part. The ring element is formed of a material that shrinks relative to the stem by sintering. The ring element may include a split collet (44C) that fits partly into the groove, and a compression ring (44E) around the collet. The non-threaded contact surface and a mating distal surface (48) of the ring element may have conic geometries (64). After shrinkage, the ring element is locked onto the stem.

Arctigenin exerts anti-colitis efficacy through inhibiting the differentiation of Th1 and Th17 cells via an mTORC1-dependent pathway.

PubMed

Wu, Xin; Dou, Yannong; Yang, Yan; Bian, Difei; Luo, Jinque; Tong, Bei; Xia, Yufeng; Dai, Yue

2015-08-15

Arctigenin, the main effective constituent of Arctium lappa L. fruit, has previously been proven to dramatically attenuate dextran sulfate sodium (DSS)-induced colitis in mice, a frequently used animal model of inflammatory bowel disease (IBD). As Th1 and Th17 cells play a crucial role in the pathogenesis of IBD, the present study addressed whether and how arctigenin exerted anti-colitis efficacy by interfering with the differentiation and activation of Th1/Th17 cells. In vitro, arctigenin was shown to markedly inhibit the differentiation of Th17 cells from naïve T cells, and moderately inhibit the differentiation of Th1 cells, which was accompanied by lowered phosphorylation of STAT3 and STAT4, respectively. In contrast, arctigenin was lack of marked effect on the differentiation of either Th2 or regulatory T cells. Furthermore, arctigenin was shown to suppress the mammalian target of rapamycin complex 1 (mTORC1) pathway in T cells as demonstrated by down-regulated phosphorylation of the downstream target genes p70S6K and RPS6, and it functioned independent of two well-known upstream kinases PI3K/AKT and ERK. Arctigenin was also able to inhibit the activity of mTORC1 by dissociating raptor from mTOR. Interestingly, the inhibitory effect of arctigenin on T cell differentiation disappeared under a status of mTORC1 overactivation via knockdown of tuberous sclerosis complex 2 (TSC2, a negative regulator of mTORC1) or pretreatment of leucine (an agonist of mTOR). In DSS-induced mice, the inhibition of Th1/Th17 responses and anti-colitis effect of arctigenin were abrogated by leucine treatment. In conclusion, arctigenin ameliorates colitis through down-regulating the differentiation of Th1 and Th17 cells via mTORC1 pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

Fertility decline and social service access: reconciling behavioral and medical models.

PubMed

Weinstein, J

1978-01-01

In this summary of fertility literature the author attempts to differentiate between the effects of behavioral and medical models of family planning programs on the fertility rate. This is done by determining the effects of access to social welfare services by assessment of: the function of children within the family life survey conducted in the Cameroons are also used. It was found that 7 interdependent elements of social service are involved: 1) general health care; 2) social security for sick and aged; 3) employment training and opportunities for adults; 4) literacy and education; 5) communication and transportation systems; 6) housing and infrastructure; 7) child care and welfare. The presence of these elements is shown to accompany low fertility while their absence is expressed in high rates of child bearing. These elements are major variables in both the nomological and public policy senses. 2 additional components are knowledge of and favorable attitudes towards effective means of fertility control plus effective mechanical, chemical, or natural means of limiting fertility. The concept of fertility norm and its impact on the fertility rate is explained as being the result of the collective force which social affiliations exert on people to reproduce in a certain way. The "stopping rule" is that which will fulfill the fertility norm. An example of this is a culture which continues child bearing until a son has been born and then controls reproduction after this has happened. Such factors must be considered for family planning programs to succeed in these cultures. Therefore fertility levels are found to be the product of prevailing norms and technical ability to achieve these norms. Improvement in levels of access to social services can bring about the lowering of these norms.

Urbanization and agriculture increase exports and differentially alter elemental stoichiometry of dissolved organic matter (DOM) from tropical catchments.

PubMed

Gücker, Björn; Silva, Ricky C S; Graeber, Daniel; Monteiro, José A F; Boëchat, Iola G

2016-04-15

Many tropical biomes are threatened by rapid land-use change, but its catchment-wide biogeochemical effects are poorly understood. The few previous studies on DOM in tropical catchments suggest that deforestation and subsequent land use increase stream water dissolved organic carbon (DOC) concentrations, but consistent effects on DOM elemental stoichiometry have not yet been reported. Here, we studied stream water DOC concentrations, catchment DOC exports, and DOM elemental stoichiometry in 20 tropical catchments at the Cerrado-Atlantic rainforest transition, dominated by natural vegetation, pasture, intensive agriculture, and urban land cover. Streams draining pasture could be distinguished from those draining natural catchments by their lower DOC concentrations, with lower DOM C:N and C:P ratios. Catchments with intensive agriculture had higher DOC exports and lower DOM C:P ratios than natural catchments. Finally, with the highest DOC concentrations and exports, as well as the highest DOM C:P and N:P ratios, but the lowest C:N ratios among all land-use types, urbanized catchments had the strongest effects on catchment DOM. Thus, urbanization may have alleviated N limitation of heterotrophic DOM decomposition, but increased P limitation. Land use-especially urbanization-also affected the seasonality of catchment biogeochemistry. While natural catchments exhibited high DOC exports and concentrations, with high DOM C:P ratios in the rainy season only, urbanized catchments had high values in these variables throughout the year. Our results suggest that urbanization and pastoral land use exerted the strongest impacts on DOM biogeochemistry in the investigated tropical catchments and should thus be important targets for management and mitigation efforts. Copyright © 2016 Elsevier B.V. All rights reserved.

The Effect of Volumetric Porosity on Roughness Element Drag

NASA Astrophysics Data System (ADS)

Gillies, John; Nickling, William; Nikolich, George; Etyemezian, Vicken

2016-04-01

Much attention has been given to understanding how the porosity of two dimensional structures affects the drag force exerted by boundary-layer flow on these flow obstructions. Porous structures such as wind breaks and fences are typically used to control the sedimentation of sand and snow particles or create micro-habitats in their lee. Vegetation in drylands also exerts control on sediment transport by wind due to aerodynamic effects and interaction with particles in transport. Recent research has also demonstrated that large spatial arrays of solid three dimensional roughness elements can be used to reduce sand transport to specified targets for control of wind erosion through the effect of drag partitioning and interaction of the moving sand with the large (>0.3 m high) roughness elements, but porous elements may improve the effectiveness of this approach. A thorough understanding of the role porosity plays in affecting the drag force on three-dimensional forms is lacking. To provide basic understanding of the relationship between the porosity of roughness elements and the force of drag exerted on them by fluid flow, we undertook a wind tunnel study that systematically altered the porosity of roughness elements of defined geometry (cubes, rectangular cylinders, and round cylinders) and measured the associated change in the drag force on the elements under similar Reynolds number conditions. The elements tested were of four basic forms: 1) same sized cubes with tubes of known diameter milled through them creating three volumetric porosity values and increasing connectivity between the tubes, 2) cubes and rectangular cylinders constructed of brass screen that nested within each other, and 3) round cylinders constructed of brass screen that nested within each other. The two-dimensional porosity, defined as the ratio of total surface area of the empty space to the solid surface area of the side of the element presented to the fluid flow was conserved at 0.519 for the cubes and 0.525 for the mesh forms. Results from the study indicate that as volumetric porosity increases, the force of drag on an element increases although the 2-dimensional porosity remains unchanged for the case of the cube forms. The mesh forms show a similar result that with increasing number of internal forms present, drag increases, but the drag curves are different, suggesting the kind of porosity has an effect on drag. An important scaling parameter that controls drag on the cubes is the permeability (K) of the element, which is a function of the diameter of the tubes and the porosity. K seems to be of lesser importance for controlling drag on the mesh forms. We hypothesize that the drag force data do not universally collapse as a function of permeability due to Reynolds number dependency on flow conditions within the elements that can be laminar, transitional, or turbulent even though flow exterior to the forms is fully turbulent. For the mesh forms, the greatest effect on drag occurs with the addition of the first internal form with subsequent additions showing very little additional effect.

An electric-analog simulation of elliptic partial differential equations using finite element theory

USGS Publications Warehouse

Franke, O.L.; Pinder, G.F.; Patten, E.P.

1982-01-01

Elliptic partial differential equations can be solved using the Galerkin-finite element method to generate the approximating algebraic equations, and an electrical network to solve the resulting matrices. Some element configurations require the use of networks containing negative resistances which, while physically realizable, are more expensive and time-consuming to construct. ?? 1982.

Method of pedestal and common-mode noise correction for switched-capacitor analog memories

DOEpatents

Britton, Charles L.

1996-01-01

A method and apparatus for correcting common-mode noise and pedestal noise in a multichannel array of switched-capacitor analog memories wherein each analog memory is connected to an associated analog-to-digital converter. The apparatus comprises a single differential element in two different embodiments. In a first embodiment, the differential element is a reference analog memory connected to a buffer. In the second embodiment, the differential element is a reference analog memory connected to a reference analog-to-digital connected to an array of digital summing circuits.

fussel (fuss)--A negative regulator of BMP signaling in Drosophila melanogaster.

PubMed

Fischer, Susanne; Bayersdorfer, Florian; Harant, Eva; Reng, Renate; Arndt, Stephanie; Bosserhoff, Anja-Katrin; Schneuwly, Stephan

2012-01-01

The TGF-β/BMP signaling cascades control a wide range of developmental and physiological functions in vertebrates and invertebrates. In Drosophila melanogaster, members of this pathway can be divided into a Bone Morphogenic Protein (BMP) and an Activin-ß (Act-ß) branch, where Decapentaplegic (Dpp), a member of the BMP family has been most intensively studied. They differ in ligands, receptors and transmitting proteins, but also share some components, such as the Co-Smad Medea (Med). The essential role of Med is to form a complex with one of the two activating Smads, mothers against decapentaplegic (Mad) or dSmad, and to translocate together to the nucleus where they can function as transcriptional regulators of downstream target genes. This signaling cascade underlies different mechanisms of negative regulation, which can be exerted by inhibitory Smads, such as daughters against decapentaplegic (dad), but also by the Ski-Sno family. In this work we identified and functionally analyzed a new member of the Ski/Sno-family, fussel (fuss), the Drosophila homolog of the human functional suppressing element 15 (fussel-15). fuss codes for two differentially spliced transcripts with a neuronal expression pattern. The proteins are characterized by a Ski-Sno and a SAND homology domain. Overexpression studies and genetic interaction experiments clearly reveal an interaction of fuss with members of the BMP pathway, leading to a strong repression of BMP-signaling. The protein interacts directly with Medea and seems to reprogram the Smad pathway through its influence upon the formation of functional Mad/Medea complexes. This leads amongst others to a repression of downstream target genes of the Dpp pathway, such as optomotor blind (omb). Taken together we could show that fuss exerts a pivotal role as an antagonist of BMP signaling in Drosophila melanogaster.

Histone deacetylase inhibitors suppress ABO transcription in vitro, leading to reduced expression of the antigens.

PubMed

Takahashi, Yoichiro; Kubo, Rieko; Sano, Rie; Nakajima, Tamiko; Takahashi, Keiko; Kobayashi, Momoko; Handa, Hiroshi; Tsukada, Junichi; Kominato, Yoshihiko

2017-03-01

The ABO system is of fundamental importance in the fields of transfusion and transplantation and has apparent associations with certain diseases, including cardiovascular disorders. ABO expression is reduced in the late phase of erythroid differentiation in vitro, whereas histone deacetylase inhibitors (HDACIs) are known to promote cell differentiation. Therefore, whether or not HDACIs could reduce the amount of ABO transcripts and A or B antigens is an intriguing issue. Quantitative polymerase chain reactions were carried out for the ABO transcripts in erythroid-lineage K562 and epithelial-lineage KATOIII cells after incubation with HDACIs, such as sodium butyrate, panobinostat, vorinostat, and sodium valproate. Flow cytometric analysis was conducted to evaluate the amounts of antigen in KATOIII cells treated with panobinostat. Quantitative chromatin immunoprecipitation (ChIP) assays and luciferase assays were performed on both cell types to examine the mechanisms of ABO suppression. HDACIs reduced the ABO transcripts in both K562 and KATOIII cells, with panobinostat exerting the most significant effect. Flow cytometric analysis demonstrated a decrease in B-antigen expression on panobinostat-treated KATOIII cells. ChIP assays indicated that panobinostat altered the modification of histones in the transcriptional regulatory regions of ABO, and luciferase assays demonstrated reduced activity of these elements. ABO transcription seems to be regulated by an epigenetic mechanism. Panobinostat appears to suppress ABO transcription, reducing the amount of antigens on the surface of cultured cells. © 2016 AABB.

The biomechanical effects of variation in the maximum forces exerted by trunk muscles on the joint forces and moments in the lumbar spine: a finite element analysis.

PubMed

Kim, K; Lee, S K; Kim, Y H

2010-10-01

The weakening of trunk muscles is known to be related to a reduction of the stabilization function provided by the muscles to the lumbar spine; therefore, strengthening deep muscles might reduce the possibility of injury and pain in the lumbar spine. In this study, the effect of variation in maximum forces of trunk muscles on the joint forces and moments in the lumbar spine was investigated. Accordingly, a three-dimensional finite element model of the lumbar spine that included the trunk muscles was used in this study. The variation in maximum forces of specific muscle groups was then modelled, and joint compressive and shear forces, as well as resultant joint moments, which were presumed to be related to spinal stabilization from a mechanical viewpoint, were analysed. The increase in resultant joint moments occurred owing to decrease in maximum forces of the multifidus, interspinales, intertransversarii, rotatores, iliocostalis, longissimus, psoas, and quadratus lumborum. In addition, joint shear forces and resultant joint moments were reduced as the maximum forces of deep muscles were increased. These results from finite element analysis indicate that the variation in maximum forces exerted by trunk muscles could affect the joint forces and joint moments in the lumbar spine.

Sulforaphane plays common and different roles in tumorigenic and nontumorigenic colon cell growth

USDA-ARS?s Scientific Manuscript database

Sulforaphane (SFN) is a naturally occurring member of the isothiocyanate family of chemopreventive agents and the induction of cell cycle arrest and apoptosis is a key mechanism by which SFN exerts its colon cancer prevention. However, little is known about the differential effects of SFN on colon c...

Examining the Differential Effectiveness of a Life Skills Program (IPSY) on Alcohol Use Trajectories in Early Adolescence

ERIC Educational Resources Information Center

Spaeth, Michael; Weichold, Karina; Silbereisen, Rainer K.; Wiesner, Margit

2010-01-01

Objective: This study investigated whether a universal school-based life skills program--IPSY (Information + Psychosocial Competence = Protection)--against substance misuse exerted the same effectiveness for young adolescents (10.5-13 years) from distinct alcohol use trajectories characterized by late childhood risk factors (temperament,…

Differential Sensitivity of Target Genes to Translational Repression by miR-17~92

PubMed Central

Jin, Hyun Yong; Oda, Hiroyo; Chen, Pengda; Kang, Seung Goo; Valentine, Elizabeth; Liao, Lujian; Zhang, Yaoyang; Gonzalez-Martin, Alicia; Shepherd, Jovan; Head, Steven R.; Kim, Pyeung-Hyeun; Fu, Guo; Liu, Wen-Hsien; Han, Jiahuai

2017-01-01

MicroRNAs (miRNAs) are thought to exert their functions by modulating the expression of hundreds of target genes and each to a small degree, but it remains unclear how small changes in hundreds of target genes are translated into the specific function of a miRNA. Here, we conducted an integrated analysis of transcriptome and translatome of primary B cells from mutant mice expressing miR-17~92 at three different levels to address this issue. We found that target genes exhibit differential sensitivity to miRNA suppression and that only a small fraction of target genes are actually suppressed by a given concentration of miRNA under physiological conditions. Transgenic expression and deletion of the same miRNA gene regulate largely distinct sets of target genes. miR-17~92 controls target gene expression mainly through translational repression and 5’UTR plays an important role in regulating target gene sensitivity to miRNA suppression. These findings provide molecular insights into a model in which miRNAs exert their specific functions through a small number of key target genes. PMID:28241004

TGF-beta1 modulates focal adhesion kinase expression in rat intestinal epithelial IEC-6 cells via stimulatory and inhibitory Smad binding elements.

PubMed

Walsh, Mary F; Ampasala, Dinakar R; Rishi, Arun K; Basson, Marc D

2009-02-01

TGF-beta and FAK modulate cell migration, differentiation, proliferation and apoptosis, and TGF-beta promotes FAK transcription in intestinal epithelial cells via Smad-dependent and independent pathways. We utilized a 1320 bp FAK promoter-luciferase construct to characterize basal and TGF-beta-mediated FAK gene transcription in IEC-6 cells. Inhibiting JNK or Akt negated TGF-beta-stimulated promoter activity; ERK inhibition did not block the TGF-beta effect but increased basal activity. Co-transfection with Co-Smad4 enhanced the TGF-beta response while the inhibitory Smad7 abolished it. Serial deletions sequentially removing the four Smad binding elements (SBE) in the 5' untranslated region of the promoter revealed that the two most distal SBE's are positive regulators while SBE3 exerts a negative influence. Mutational deletion of two upstream p53 sites enhanced basal but did not affect TGF-beta-stimulated increases in promoter activity. TGF-beta increased DNA binding of Smad4, phospho-Smad2/3 and Runx1/AML1a to the most distal 435 bp containing 3 SBE and 2 AML1a sites by ChIP assay. However, although point mutation of SBE1 ablated the TGF-beta-mediated rise in SV40-promoter activity, mutation of AML1a sites did not. TGF-beta regulation of FAK transcription reflects a complex interplay between positive and negative non-Smad signals and SBE's, the last independent of p53 or AML1a.

Influence of microgravity on cellular differentiation in root caps of Zea mays

NASA Technical Reports Server (NTRS)

Moore, R.; Fondren, W. M.; McClelen, C. E.; Wang, C. L.

1987-01-01

We launched imbibed seeds of Zea mays into outer space aboard the space shuttle Columbia to determine the influence of microgravity on cellular differentiation in root caps. The influence of microgravity varied with different stages of cellular differentiation. Overall, microgravity tended to 1) increase relative volumes of hyaloplasm and lipid bodies, 2) decrease the relative volumes of plastids, mitochondria, dictyosomes, and the vacuome, and 3) exert no influence on the relative volume of nuclei in cells comprising the root cap. The reduced allocation of dictyosomal volume in peripheral cells of flight-grown seedlings correlated positively with their secretion of significantly less mucilage than peripheral cells of Earth-grown seedlings. These results indicate that 1) microgravity alters the patterns of cellular differentiation and structures of all cell types comprising the root cap, and 2) the influence of microgravity on cellular differentiation in root caps of Zea mays is organelle specific.

Sieve-element differentiation and phloem sap contamination.

PubMed

Knoblauch, Michael; Peters, Winfried S; Bell, Karen; Ross-Elliott, Timothy J; Oparka, Karl J

2018-06-01

Sieve elements (SEs) degrade selected organelles and cytoplasmic structures when they differentiate. According to classical investigations, only smooth ER, mitochondria, sieve element plastids, and, in most cases, P-proteins remain in mature SEs. More recent proteomics and immuno-histochemical studies, however, suggested that additional components including a protein-synthesizing machinery and a fully developed actin cytoskeleton operate in mature SEs. These interpretations are at odds with conventional imaging studies. Here we discuss potential causes for these discrepancies, concluding that differentiating SEs may play a role by 'contaminating' phloem exudates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Method of pedestal and common-mode noise correction for switched-capacitor analog memories

DOEpatents

Britton, C.L.

1996-12-31

A method and apparatus are disclosed for correcting common-mode noise and pedestal noise in a multichannel array of switched-capacitor analog memories wherein each analog memory is connected to an associated analog-to-digital converter. The apparatus comprises a single differential element in two different embodiments. In a first embodiment, the differential element is a reference analog memory connected to a buffer. In the second embodiment, the differential element is a reference analog memory connected to a reference analog-to-digital connected to an array of digital summing circuits. 4 figs.

A Simple Method for Decreasing the Liquid Junction Potential in a Flow-through-Type Differential pH Sensor Probe Consisting of pH-FETs by Exerting Spatiotemporal Control of the Liquid Junction

PubMed Central

Yamada, Akira; Mohri, Satoshi; Nakamura, Michihiro; Naruse, Keiji

2015-01-01

The liquid junction potential (LJP), the phenomenon that occurs when two electrolyte solutions of different composition come into contact, prevents accurate measurements in potentiometry. The effect of the LJP is usually remarkable in measurements of diluted solutions with low buffering capacities or low ion concentrations. Our group has constructed a simple method to eliminate the LJP by exerting spatiotemporal control of a liquid junction (LJ) formed between two solutions, a sample solution and a baseline solution (BLS), in a flow-through-type differential pH sensor probe. The method was contrived based on microfluidics. The sensor probe is a differential measurement system composed of two ion-sensitive field-effect transistors (ISFETs) and one Ag/AgCl electrode. With our new method, the border region of the sample solution and BLS is vibrated in order to mix solutions and suppress the overshoot after the sample solution is suctioned into the sensor probe. Compared to the conventional method without vibration, our method shortened the settling time from over two min to 15 s and reduced the measurement error by 86% to within 0.060 pH. This new method will be useful for improving the response characteristics and decreasing the measurement error of many apparatuses that use LJs. PMID:25835300

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.

Hydroxyframoside B, a secoiridoid of Fraxinus rhynchophylla, inhibits adipocyte differentiation in 3T3-L1 cells.

PubMed

Choi, Kyeong-Mi; Shin, Eunjin; Liu, Qing; Yoo, Hwan-Soo; Kim, Young Choong; Sung, Sang Hyun; Hwang, Bang Yeon; Lee, Mi Kyeong

2011-07-01

Fraxinus rhynchophylla showed significant inhibitory activity on adipocyte differentiation in the 3T3-L1 preadipocyte cell line as assessed by measuring fat accumulation using Oil Red O staining. Further fractionation led to the isolation of two secoiridoids, oleuropein and hydroxyframoside B. Hydroxyframoside B significantly reduced fat accumulation and triglyceride content in differentiated 3T3-L1 cells without affecting cell viability, whereas oleuropein showed little effect. Further studies with interval treatment demonstrated that hydroxyframoside B exerted inhibitory activity on adipocyte differentiation when treated within 2 days (days 0-2) after differentiation induction. In addition, hydroxyframoside B significantly blocked the induction of adipogenic transcription factors such as C/EBP α, C/EBP β, and PPAR γ. Taken together, these results suggest that hydroxyframoside B inhibited early/middle stage of adipogenic differentiation, in part, via inhibition of C/EBP α, C/EBP β, and PPAR γ-dependent pathways. © Georg Thieme Verlag KG Stuttgart · New York.

Elimination of secular terms from the differential equations for the elements of perturbed two-body motion

NASA Technical Reports Server (NTRS)

Bond, Victor R.; Fraietta, Michael F.

1991-01-01

In 1961, Sperling linearized and regularized the differential equations of motion of the two-body problem by changing the independent variable from time to fictitious time by Sundman's transformation (r = dt/ds) and by embedding the two-body energy integral and the Laplace vector. In 1968, Burdet developed a perturbation theory which was uniformly valid for all types of orbits using a variation of parameters approach on the elements which appeared in Sperling's equations for the two-body solution. In 1973, Bond and Hanssen improved Burdet's set of differential equations by embedding the total energy (which is a constant when the potential function is explicitly dependent upon time.) The Jacobian constant was used as an element to replace the total energy in a reformulation of the differential equations of motion. In the process, another element which is proportional to a component of the angular momentum was introduced. Recently trajectories computed during numerical studies of atmospheric entry from circular orbits and low thrust beginning in near-circular orbits exhibited numerical instability when solved by the method of Bond and Gottlieb (1989) for long time intervals. It was found that this instability was due to secular terms which appear on the righthand sides of the differential equations of some of the elements. In this paper, this instability is removed by the introduction of another vector integral called the delta integral (which replaces the Laplace Vector) and another scalar integral which removes the secular terms. The introduction of these integrals requires a new derivation of the differential equations for most of the elements. For this rederivation, the Lagrange method of variation of parameters is used, making the development more concise. Numerical examples of this improvement are presented.

(N+1)-dimensional fractional reduced differential transform method for fractional order partial differential equations

NASA Astrophysics Data System (ADS)

Arshad, Muhammad; Lu, Dianchen; Wang, Jun

2017-07-01

In this paper, we pursue the general form of the fractional reduced differential transform method (DTM) to (N+1)-dimensional case, so that fractional order partial differential equations (PDEs) can be resolved effectively. The most distinct aspect of this method is that no prescribed assumptions are required, and the huge computational exertion is reduced and round-off errors are also evaded. We utilize the proposed scheme on some initial value problems and approximate numerical solutions of linear and nonlinear time fractional PDEs are obtained, which shows that the method is highly accurate and simple to apply. The proposed technique is thus an influential technique for solving the fractional PDEs and fractional order problems occurring in the field of engineering, physics etc. Numerical results are obtained for verification and demonstration purpose by using Mathematica software.

Five Essential Elements of Crisis Intervention for Communities and Schools When Responding to Technological Disasters

ERIC Educational Resources Information Center

Sulkowski, Michael L.; Lazarus, Philip J.

2013-01-01

Technological disasters result from human error, negligence, or limitations in perceiving and reducing risk. They are a form of manmade disaster that exerts a devastating effect on impacted individuals, communities, and ecosystems. Because of their negative impacts, technological disasters often erode community connectedness, undermine adaptive…

Prolonged Sulforaphane Treatment Activates Extracellular-Regulated Kinase 1/2 Signaling in Nontumorigenic Colon Cells but not Colon Cancer Cells

USDA-ARS?s Scientific Manuscript database

Sulforaphane (SFN) is a naturally occurring member of the isothiocyanate family of chemopreventive agents and the induction of cell cycle arrest and apoptosis is a key mechanism by which SFN exerts its colon cancer prevention. However, little is known about the differential effects of SFN on colon c...

The Effect of IQ Level on the Degree of Cognitive Deterioration Experienced during Acute Hypoglycemia in Normal Humans.

ERIC Educational Resources Information Center

Gold, Ann E.; And Others

1995-01-01

Whether IQ level exerts a differential effect on the impairment of cognitive performance induced during acute hypoglycemia was studied for 24 nondiabetic adults. At various levels of hypoglycemia, no overall effect of IQ on deterioration was noted. Higher IQ did not apparently protect against adverse effects. (SLD)

Isolating causal pathways between flow and fish in the regulated river hierarchy

Treesearch

Ryan McManamay; Donald J. Orth; Charles A. Dolloff; David C. Mathews

2015-01-01

Unregulated river systems are organized in a hierarchy in which large scale factors (i.e. landscape and segment scales) influence local habitats (i.e. reach, meso- and microhabitat scales), and both differentially exert selective pressures on biota. Dams, however, create discontinua in these processes and change the hierarchical structure. We examined the relative...

Exercise-associated Excessive Dynamic Airway Collapse in Military Personnel.

PubMed

Weinstein, Daniel J; Hull, James E; Ritchie, Brittany L; Hayes, Jackie A; Morris, Michael J

2016-09-01

Evaluation of military personnel for exertional dyspnea can present a diagnostic challenge, given multiple unique factors that include wide variation in military deployment. Initial consideration is given to common disorders such as asthma, exercise-induced bronchospasm, and inducible laryngeal obstruction. Excessive dynamic airway collapse has not been reported previously as a cause of dyspnea in these individuals. To describe the clinical and imaging characteristics of military personnel with exertional dyspnea who were found to have excessive dynamic collapse of large airways during exercise. After deployment to Afghanistan or Iraq, 240 active U.S. military personnel underwent a standardized evaluation to determine the etiology of persistent dyspnea on exertion. Study procedures included full pulmonary function testing, impulse oscillometry, exhaled nitric oxide measurement, methacholine challenge testing, exercise laryngoscopy, cardiopulmonary exercise testing, and fiberoptic bronchoscopy. Imaging included high-resolution computed tomography with inspiratory and expiratory views. Selected individuals underwent further imaging with dynamic computed tomography. A total of five men and one woman were identified as having exercise-associated excessive dynamic airway collapse on the basis of the following criteria: (1) exertional dyspnea without resting symptoms, (2) focal expiratory wheezing during exercise, (3) functional collapse of the large airways during bronchoscopy, (4) expiratory computed tomographic imaging showing narrowing of a large airway, and (5) absence of underlying apparent pathology in small airways or pulmonary parenchyma. Identification of focal expiratory wheezing correlated with bronchoscopic and imaging findings. Among 240 military personnel evaluated after presenting with postdeployment exertional dyspnea, a combination of symptoms, auscultatory findings, imaging, and visualization of the airways by bronchoscopy identified six individuals with excessive dynamic central airway collapse as the sole apparent cause of dyspnea. Exercise-associated excessive dynamic airway collapse should be considered in the differential diagnosis of exertional dyspnea.

Differential Regulation of Native Estrogen Receptor-Regulatory Elements by Estradiol, Tamoxifen, and Raloxifene

PubMed Central

Levy, Nitzan; Tatomer, Dierdre; Herber, Candice B.; Zhao, Xiaoyue; Tang, Hui; Sargeant, Toby; Ball, Lonnele J.; Summers, Jonathan; Speed, Terence P.; Leitman, Dale C.

2008-01-01

Estrogen receptors (ERs) regulate gene transcription by interacting with regulatory elements. Most information regarding how ER activates genes has come from studies using a small set of target genes or simple consensus sequences such as estrogen response element, activator protein 1, and Sp1 elements. However, these elements cannot explain the differences in gene regulation patterns and clinical effects observed with estradiol (E2) and selective estrogen receptor modulators. To obtain a greater understanding of how E2 and selective estrogen receptor modulators differentially regulate genes, it is necessary to investigate their action on a more comprehensive set of native regulatory elements derived from ER target genes. Here we used chromatin immunoprecipitation-cloning and sequencing to isolate 173 regulatory elements associated with ERα. Most elements were found in the introns (38%) and regions greater than 10 kb upstream of the transcription initiation site (38%); 24% of the elements were found in the proximal promoter region (<10 kb). Only 11% of the elements contained a classical estrogen response element; 23% of the elements did not have any known response elements, including one derived from the naked cuticle homolog gene, which was associated with the recruitment of p160 coactivators. Transfection studies found that 80% of the 173 elements were regulated by E2, raloxifene, or tamoxifen with ERα or ERβ. Tamoxifen was more effective than raloxifene at activating the elements with ERα, whereas raloxifene was superior with ERβ. Our findings demonstrate that E2, tamoxifen, and raloxifene differentially regulate native ER-regulatory elements isolated by chromatin immunoprecipitation with ERα and ERβ. PMID:17962382

Chronic Exertional Compartment Syndrome.

PubMed

Braver, Richard T

2016-04-01

Increased tissue pressure within a fascial compartment may be the result from any increase in volume within its contents, or any decrease in size of the fascial covering or its distensibility. This may lead to symptoms of leg tightness, pain or numbness brought about by exercise. There are multiple differential diagnoses of exercise induced leg pain and the proper diagnoses of chronic exertional compartment syndrome (CECS) is made by a careful history and by exclusion of other maladies and confirmed by compartment syndrome testing as detailed in this text. Surgical fasciotomies for the anterior, lateral, superficial and deep posterior compartments are described in detail along with ancillary procedures for chronic shin splints that should allow the athlete to return to competitive activity. Copyright © 2016 Elsevier Inc. All rights reserved.

Determinants of rural and urban fertility differentials in Nigeria.

PubMed

Chimere-Dan, O

1990-07-01

Whatever proximate variables are examined, their differential effects on rural and urban fertility are small. This indicates that no major disturbance has taken place in urban or rural reproductive norms. However, two possible reasons for the converging pattern of rural and urban fertility in Nigeria are identified. One is that urban mothers in the first half of the childbearing age range have higher fertility than their rural counterparts. The other is that breast-feeding and post-partum abstinence, which are the major determinants of marital fertility, exert a more depressing influence on rural than urban fertility.

One- and two-dimensional antenna arrays for microwave wireless power transfer (MWPT) systems and dual-antenna transceivers

NASA Astrophysics Data System (ADS)

Lin, Yo-Sheng; Hu, Chun-Hao; Chang, Chi-Ho; Tsao, Ping-Chang

2018-06-01

In this work, we demonstrate novel one-dimensional (1D) and two-dimensional (2D) antenna arrays for both microwave wireless power transfer (MWPT) systems and dual-antenna transceivers. The antenna array can be used as the MWPT receiving antenna of an integrated MWPT and Bluetooth (BLE) communication module (MWPT-BLE module) for smart CNC (computer numerical control) spindle incorporated with the cloud computing system SkyMars. The 2D antenna array has n rows of 1 × m 1D array, and each array is composed of multiple (m) differential feeding antenna elements. Each differential feeding antenna element is a differential feeding structure with a microstrip antenna stripe. The stripe length is shorter than one wavelength to minimise the antenna area and to prevent being excited to a high-order mode. That is, the differential feeding antenna element can suppress the even mode. The mutual coupling between the antenna elements can be suppressed, and the isolation between the receiver and the transmitter can be enhanced. An inclination angle of the main beam aligns with the broadside, and the main beam is further concentrated and shrunk at the elevation direction. Moreover, if more differential feeding antenna elements are used, antenna gain and isolation can be further enhanced. The excellent performance of the proposed antenna arrays indicates that they are suitable for both MWPT systems and dual-antenna transceivers.

Molecular basis for zinc potentiation at strychnine-sensitive glycine receptors.

PubMed

Miller, Paul S; Da Silva, Helena M A; Smart, Trevor G

2005-11-11

The divalent cation Zn(2+) is a potent potentiator at the strychnine-sensitive glycine receptor (GlyR). This occurs at nanomolar concentrations, which are the predicted endogenous levels of extracellular neuronal Zn(2+). Using structural modeling and functional mutagenesis, we have identified the molecular basis for the elusive Zn(2+) potentiation site on GlyRs and account for the differential sensitivity of GlyR alpha(1) and GlyR alpha(2) to Zn(2+) potentiation. In addition, juxtaposed to this Zn(2+) site, which is located externally on the N-terminal domain of the alpha subunit, another residue was identified in the nearby Cys loop, a region that is critical for receptor gating in all Cys loop ligand-gated ion channels. This residue acted as a key control element in the allosteric transduction pathway for Zn(2+) potentiation, enabling either potentiation or overt inhibition of receptor activation depending upon the moiety resident at this location. Overall, we propose that Zn(2+) binds to a site on the extracellular outer face of the GlyR alpha subunit and exerts its positive allosteric effect via an interaction with the Cys loop to increase the efficacy of glycine receptor gating.

ICI 182,780-regulated gene expression in DU145 prostate cancer cells is mediated by estrogen receptor-beta/NFkappaB crosstalk.

PubMed

Leung, Yuet-Kin; Gao, Ying; Lau, Kin-Mang; Zhang, Xiang; Ho, Shuk-Mei

2006-04-01

Estrogen receptor (ER)-beta is the predominant ER subtype in prostate cancer (PCa). We previously demonstrated that ICI 182,780 (ICI), but not estrogens, exerted dose-dependent growth inhibition on DU145 PCa cells by an ER-beta-mediated pathway. Transcriptional profiling detected a greater than three-fold upregulation of seven genes after a 12-hour exposure to 1 microM ICI. Semiquantitative reverse transcriptase polymerase chain reaction confirmed the upregulation of four genes by ICI: interleukin-12alpha chain, interleukin-8, embryonic growth/differentiation factor, and RYK tyrosine kinase. Treatment with an ER-beta antisense oligonucleotide reduced cellular ER-beta mRNA and induced loss of expression of these genes. Sequence analysis revealed the presence of consensus NFkappaB sites, but not estrogen-responsive elements, in promoters of all four genes. Reporter assay and chromatin immunoprecipitation experiments demonstrated that ICI-induced gene expression could be mediated by crosstalk between ER-beta and the NFkappaB signaling pathway, denoting a novel mechanism of ER-beta-mediated ICI action. Therefore, combined therapies targeting ER-beta and NFkappaB signaling may be synergistic as treatment for PCa.

ICI 182,780-Regulated Gene Expression in DU145 Prostate Cancer Cells Is Mediated by Estrogen Receptor-β/NFκB Crosstalk1

PubMed Central

Leung, Yuet-Kin; Gao, Ying; Lau, Kin-Mang; Zhang, Xiang; Ho, Shuk-Mei

2006-01-01

Abstract Estrogen receptor (ER)-β is the predominant ER subtype in prostate cancer (PCa). We previously demonstrated that ICI 182,780 (ICI), but not estrogens, exerted dose-dependent growth inhibition on DU145 PCa cells by an ER-β-mediated pathway. Transcriptional profiling detected a greater than three-fold upregulation of seven genes after a 12-hour exposure to 1 µM ICI. Semi-quantitative reverse transcriptase polymerase chain reaction confirmed the upregulation of four genes by ICI: interleukin-12α chain, interleukin-8, embryonic growth/differentiation factor, and RYK tyrosine kinase. Treatment with an ER-β antisense oligonucleotide reduced cellular ER-β mRNA and induced loss of expression of these genes. Sequence analysis revealed the presence of consensus NFκB sites, but not estrogen-responsive elements, in promoters of all four genes. Reporter assay and chromatin immunoprecipitation experiments demonstrated that ICI-induced gene expression could be mediated by crosstalk between ER-α and the NFκB signaling pathway, denoting a novel mechanism of ER-β-mediated ICI action. Therefore, combined therapies targeting ER-β and NFκB signaling may be synergistic as treatment for PCa. PMID:16756716

Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Pathway Is Induced by Mechanical Load and Reduces the Activity of Hedgehog Signaling in Chondrogenic Micromass Cell Cultures

PubMed Central

Juhász, Tamás; Szentléleky, Eszter; Szűcs Somogyi, Csilla; Takács, Roland; Dobrosi, Nóra; Engler, Máté; Tamás, Andrea; Reglődi, Dóra; Zákány, Róza

2015-01-01

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurohormone exerting protective function during various stress conditions either in mature or developing tissues. Previously we proved the presence of PACAP signaling elements in chicken limb bud-derived chondrogenic cells in micromass cell cultures. Since no data can be found if PACAP signaling is playing any role during mechanical stress in any tissues, we aimed to investigate its contribution in mechanotransduction during chondrogenesis. Expressions of the mRNAs of PACAP and its major receptor, PAC1 increased, while that of other receptors, VPAC1, VPAC2 decreased upon mechanical stimulus. Mechanical load enhanced the expression of collagen type X, a marker of hypertrophic differentiation of chondrocytes and PACAP addition attenuated this elevation. Moreover, exogenous PACAP also prevented the mechanical load evoked activation of hedgehog signaling: protein levels of Sonic and Indian Hedgehogs and Gli1 transcription factor were lowered while expressions of Gli2 and Gli3 were elevated by PACAP application during mechanical load. Our results suggest that mechanical load activates PACAP signaling and exogenous PACAP acts against the hypertrophy inducing effect of mechanical load. PMID:26230691

Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Pathway Is Induced by Mechanical Load and Reduces the Activity of Hedgehog Signaling in Chondrogenic Micromass Cell Cultures.

PubMed

Juhász, Tamás; Szentléleky, Eszter; Somogyi, Csilla Szűcs; Takács, Roland; Dobrosi, Nóra; Engler, Máté; Tamás, Andrea; Reglődi, Dóra; Zákány, Róza

2015-07-29

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurohormone exerting protective function during various stress conditions either in mature or developing tissues. Previously we proved the presence of PACAP signaling elements in chicken limb bud-derived chondrogenic cells in micromass cell cultures. Since no data can be found if PACAP signaling is playing any role during mechanical stress in any tissues, we aimed to investigate its contribution in mechanotransduction during chondrogenesis. Expressions of the mRNAs of PACAP and its major receptor, PAC1 increased, while that of other receptors, VPAC1, VPAC2 decreased upon mechanical stimulus. Mechanical load enhanced the expression of collagen type X, a marker of hypertrophic differentiation of chondrocytes and PACAP addition attenuated this elevation. Moreover, exogenous PACAP also prevented the mechanical load evoked activation of hedgehog signaling: protein levels of Sonic and Indian Hedgehogs and Gli1 transcription factor were lowered while expressions of Gli2 and Gli3 were elevated by PACAP application during mechanical load. Our results suggest that mechanical load activates PACAP signaling and exogenous PACAP acts against the hypertrophy inducing effect of mechanical load.

Analysis and synthesis of distributed-lumped-active networks by digital computer

NASA Technical Reports Server (NTRS)

1973-01-01

The use of digital computational techniques in the analysis and synthesis of DLA (distributed lumped active) networks is considered. This class of networks consists of three distinct types of elements, namely, distributed elements (modeled by partial differential equations), lumped elements (modeled by algebraic relations and ordinary differential equations), and active elements (modeled by algebraic relations). Such a characterization is applicable to a broad class of circuits, especially including those usually referred to as linear integrated circuits, since the fabrication techniques for such circuits readily produce elements which may be modeled as distributed, as well as the more conventional lumped and active ones.

The muscle creatine kinase gene is regulated by multiple upstream elements, including a muscle-specific enhancer

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

Jaynes, J.B.; Johnson, J.E.; Buskin, J.N.

1988-01-01

Muscle creatine kinase (MCK) is induced to high levels during skeletal muscle differentiation. The authors examined the upstream regulatory elements of the mouse MCK gene which specify its activation during myogenesis in culture. Fusion genes containing up to 3,300 nucleotides (nt) of MCK 5' flanking DNA in various positions and orientations relative to the bacterial chloramphenicol acetyltransferase (CAT) structural gene were transfected into cultured cells. Transient expression of CAT was compared between proliferating and differentiated MM14 mouse myoblasts and with nonmyogenic mouse L cells. The major effector of high-level expression was found to have the properties of a transcriptional enhancer.more » This element, located between 1,050 and 1,256 nt upstream of the transcription start site, was also found to have a major influence on the tissue and differentiation specificity of MCK expression; it activated either the MCK promoter or heterologous promoters only in differentiated muscle cells. Comparisons of viral and cellular enhancer sequences with the MCK enhancer revealed some similarities to essential regions of the simian virus 40 enhancer as well as to a region of the immunoglobulin heavy-chain enhancer, which has been implicated in tissue-specific protein binding. Even in the absence of the enhancer, low-level expression from a 776-nt MCK promoter retained differentiation specificity. In addition to positive regulatory elements, our data provide some evidence for negative regulatory elements with activity in myoblasts. These may contribute to the cell type and differentiation specificity of MCK expression.« less

Reservoir and aquifer characterization of fluvial architectural elements: Stubensandstein, Upper Triassic, southwest Germany

NASA Astrophysics Data System (ADS)

Hornung, Jens; Aigner, Thomas

1999-12-01

This paper aims at a quantitative sedimentological and petrophysical characterization of a terminal alluvial plain system exemplified by the Stubensandstein, South German Keuper Basin. The study follows the outcrop-analogue approach, where information derived from outcrops is collected in order to enhance interpretation of comparable subsurface successions. Quantitative data on sandbody geometries, porosities and permeabilities are presented in order to constrain modelling of subsurface sandbodies and permeability barriers. For sedimentological characterization the method of architectural element analysis (Miall, A.D., 1996. The Geology of Fluvial Deposits. Springer, Berlin) was used, and modified to include poroperm facies. A special photo-technique with a precise theodolite survey was developed to create optically corrected photomosaics for outcrop wall maps from up to 20,000 m 2 large outcrops. Nine architectural elements have been classified and quantified. Bedload, mixed-load and suspended-load channel fills are separated. The petrophysical characterization of the architectural elements integrated porosity and permeability measurements of core-plugs with gamma-ray measurements along representative sections. It could be demonstrated, that certain architectural elements show a characteristic poroperm facies. Four scales of sedimentary cycles have been recognized in the Stubensandstein. Cyclic sedimentation causes changing lithofacies patterns within the architectural elements, depending on their position in the sedimentary cycle. Stratigraphic position exerts only some, paleogeographic position exerts significant influence on porosity and permeability of the sandbodies. The highest poroperm values were found in proximal areas of the alluvial plain and in middle parts within sedimentary macrocycles. The strong internal heterogeneity on the alluvial plain system is important for its reservoir and aquifer characteristics. Compartments of bedload channel sandstones in medial positions of a stratigraphic cycle represent very good reservoirs or aquifers. The seals or aquicludes are formed by extensive floodplain claystones, lacustrine sediments, paleosols, and suspended-load deposits. Strongly cemented zones of sandstones represent aquitards.

Minor elements in Keweenawan lavas, Michigan

USGS Publications Warehouse

Cornwall, H.R.; Rose, H.J.

1957-01-01

The distribution of minor elements in three basaltic flows of the Keweenawan series, of Michigan, is related to differentiation in the flows. Thus, nickel is most abundant in the early differentiates; nickel, chromium, and barium are generally deficient in the pegmatites, which formed late; whereas copper, vanadium, yttrium, and other minor elements are concentrated in the pegmatites. The minor-element content of individual minerals in the Greenstone flow varies markedly from one mineral to another and seems to depend primarily on the presence or absence in the minerals of major elements for which the minor elements can substitute. Minor elements have substituted most readily for those major elements with similar ionic radii. Valence and electronegativity also seem to influence the ease of substitution. The distribution of other minor elements in copper-bearing lodes of the Michigan copper district shows no apparent relation to copper mineralization. ?? 1957.

Whole body-element composition of Atlantic salmon Salmo salar influenced by migration direction and life stage in three distinct populations.

PubMed

Ebel, J D; Leroux, S J; Robertson, M J; Dempson, J B

2016-11-01

Body-element content was measured for three life stages of wild Atlantic salmon Salmo salar from three distinct Newfoundland populations as individuals crossed between freshwater and marine ecosystems. Life stage explained most of the variation in observed body-element concentration whereas river of capture explained very little variation. Element composition of downstream migrating post-spawn adults (i.e. kelts) and juvenile smolts were similar and the composition of these two life stages strongly differed from adults migrating upstream to spawn. Low variation within life stages and across populations suggests that S. salar may exert rheostatic control of their body-element composition. Additionally, observed differences in trace element concentration between adults and other life stages were probably driven by the high carbon concentration in adults because abundant elements, such as carbon, can strongly influence the observed concentrations of less abundant elements. Thus, understanding variation among individuals in trace elements composition requires the measurement of more abundant elements. Changes in element concentration with ontogeny have important consequences the role of fishes in ecosystem nutrient cycling and should receive further attention. © 2016 The Fisheries Society of the British Isles.

The effect of firefighter protective garments, self-contained breathing apparatus and exertion in the heat on postural sway.

PubMed

White, Scott C; Hostler, David

2017-08-01

Fire suppression wearing thermal protective clothing (TPC) and self-contained breathing apparatus (SCBA) challenges a firefighter's balance and may explain firefighter falls. Postural control based on force plate centre of pressure (COP) was compared for healthy subjects wearing TPC and SCBA before and after 20 min of heavy physical exertion in hot conditions. Baseline measures with and without TPC and SCBA (two different SCBA cylinder masses) were compared before and after exertion that included elements of fire suppression activities in an environmental chamber. COP excursion and variability increased with exertion for TPC and SCBA conditions compared to non-stressed conditions. The two different cylinder masses had no significant effect. Wearing TPC and SCBA when physically stressed in a hot environment increases postural sway and exacerbates postural control. Subjects compensated for the extra mass and adjusted to control postural sway with the addition of TPC and SCBA, but the stress protocol amplified these adjustments. Practitioner Summary: Firefighters wear thermal protective clothing (TPC) and self-contained breathing apparatus (SCBA) when heat-stressed and fatigued. Wearing TPC and SCBA was found to negatively impact balance when stressed, but not for non-stressed or two different sized SCBA tanks. Simulating fire-ground conditions wearing TPC and SCBA should be considered for improving balance.

Two distinct auto-regulatory loops operate at the PU.1 locus in B cells and myeloid cells

PubMed Central

Leddin, Mathias; Perrod, Chiara; Hoogenkamp, Maarten; Ghani, Saeed; Assi, Salam; Heinz, Sven; Wilson, Nicola K.; Follows, George; Schönheit, Jörg; Vockentanz, Lena; Mosammam, Ali M.; Chen, Wei; Tenen, Daniel G.; Westhead, David R.; Göttgens, Berthold

2011-01-01

The transcription factor PU.1 occupies a central role in controlling myeloid and early B-cell development, and its correct lineage-specific expression is critical for the differentiation choice of hematopoietic progenitors. However, little is known of how this tissue-specific pattern is established. We previously identified an upstream regulatory cis element whose targeted deletion in mice decreases PU.1 expression and causes leukemia. We show here that the upstream regulatory cis element alone is insufficient to confer physiologic PU.1 expression in mice but requires the cooperation with other, previously unidentified elements. Using a combination of transgenic studies, global chromatin assays, and detailed molecular analyses we present evidence that PU.1 is regulated by a novel mechanism involving cross talk between different cis elements together with lineage-restricted autoregulation. In this model, PU.1 regulates its expression in B cells and macrophages by differentially associating with cell type–specific transcription factors at one of its cis-regulatory elements to establish differential activity patterns at other elements. PMID:21239694

Health Education Textbook Adoption in Texas: A Lesson in Politics and Morality

ERIC Educational Resources Information Center

Wiley, David; Barr, Elissa

2007-01-01

Textbooks are often a core element of curricula and delivery of classroom instruction and have long been a source of controversy. The textbook adoption process has become less about content and more about political/cultural pressure. Special-interest groups from the right and left exert enormous influence on textbook content through bias and…

Influence of altitude and aspect on daily variations in factors of forest fire danger

Treesearch

G. Lloyd. Hayes

1941-01-01

Altitude, in broad subdivisions, exerts recognized and well-understood effects on climate. Aspect further modifies the altitudinal influence. Many publications have dealt with the interrelations of these geographic factors with climate and life zones or have discussed variations of individual weather elements as influenced by local altitude and aspect differences and...

Osthole promotes neuronal differentiation and inhibits apoptosis via Wnt/β-catenin signaling in an Alzheimer's disease model.

PubMed

Yao, Yingjia; Gao, Zhong; Liang, Wenbo; Kong, Liang; Jiao, Yanan; Li, Shaoheng; Tao, Zhenyu; Yan, Yuhui; Yang, Jingxian

2015-12-15

Neurogenesis is the process by which neural stem cells (NSCs) proliferate and differentiate into neurons. This is diminished in several neurodegenerative disorders such as Alzheimer's disease (AD), which is characterized by the deposition of amyloid (A)β peptides and neuronal loss. Stimulating NSCs to replace lost neurons is therefore a promising approach for AD treatment. Our previous study demonstrated that osthole modulates NSC proliferation and differentiation, and may reduce Aβ protein expression in nerve cells. Here we investigated the mechanism underlying the effects of osthole on NSCs. We found that osthole enhances NSC proliferation and neuronal differentiation while suppressing apoptosis, effects that were exerted via activation of Wnt/β-catenin signaling. These results provide evidence that osthole can potentially be used as a therapeutic agent in the treatment of AD and other neurodegenerative disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed

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

2003-01-01

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

Power in the hypnotic relationship: therapeutic or abusive?

PubMed

Walling, D P; Levine, R E

1997-01-01

The unique relationship between hypnotist and subject has been theorized as one explanation for the effectiveness of hypnosis. This relationship carries a power differential, present in most therapeutic relationships, but accentuated by hypnosis. The power differential is sometimes perceived as the ability of the hypnotist to control the subject. Perceptions of hypnosis offered by stage hypnotists, the popular media, and some clinicians perpetuate the notion that the hypnotist has the ability to exert undue influence upon the client. The present article examines the relationship between hypnotist and subject focusing on issues of power and control. The authors examine the unique dynamics accompanying the use of hypnosis and their impact on the therapeutic dyad. Evidence is offered demonstrating the power differential, and how this differential can serve as either a positive or negative agent of change. Therapists should be aware of the dynamics created by using hypnosis. Implications for training therapists in the use of hypnosis are suggested.

To nudge or not to nudge: cancer screening programmes and the limits of libertarian paternalism.

PubMed

Ploug, Thomas; Holm, Søren; Brodersen, John

2012-12-01

'Nudging--and the underlying idea 'libertarian paternalism'--to an increasing degree influences policy thinking in the healthcare sector. This article discusses the influence exerted upon a woman's choice of participation in the Danish breast screening programme in light of 'libertarian paternalism'. The basic tenet of 'libertarian paternalism' is outlined and the relationship between 'libertarian paternalism' and informed consent investigated. Key elements in the process of enrolling women into the Danish mammography screening programme are introduced. It is shown that for several reasons the influence exerted upon women's choices of participation cannot be justified within a welfare-enhancing libertarian paternalistic framework. The article suggests that screening programmes alternatively adopt a liberty-enhancing approach and considers the practical implications of this alternative.

Prolonged sulforaphane treatment activates survival signaling in nontumorigenic NCM460 colon cells but apoptotic signaling in tumorigenic HCT116 colon cells

USDA-ARS?s Scientific Manuscript database

Sulforaphane (SFN) is a naturally occurring member of the isothiocyanate family of chemopreventive agents and the induction of cell cycle arrest and apoptosis is a key mechanism by which SFN exerts its colon cancer prevention. However, little is known about the differential effects of SFN on colon c...

The roles of supernatant of macrophage treated by excretory-secretory products from muscle larvae of Trichinella spiralis on the differentiation of C2C12 myoblasts

USDA-ARS?s Scientific Manuscript database

The excretory-secretory products (ESPs) released by the muscle-larvae (ML) stage of Trichinella spiralis have been suggested to be involved in nurse cell formation. However, the molecular mechanisms by which ML-ESPs modulate nurse cell formation remain unclear. Macrophages exert either beneficial or...

A Posteriori Finite Element Bounds for Sensitivity Derivatives of Partial-Differential-Equation Outputs. Revised

NASA Technical Reports Server (NTRS)

Lewis, Robert Michael; Patera, Anthony T.; Peraire, Jaume

1998-01-01

We present a Neumann-subproblem a posteriori finite element procedure for the efficient and accurate calculation of rigorous, 'constant-free' upper and lower bounds for sensitivity derivatives of functionals of the solutions of partial differential equations. The design motivation for sensitivity derivative error control is discussed; the a posteriori finite element procedure is described; the asymptotic bounding properties and computational complexity of the method are summarized; and illustrative numerical results are presented.

[Hypoxia and memory. Specific features of nootropic agents effects and their use].

PubMed

Voronina, T A

2000-01-01

Hypoxia and hypoxic adaptation are powerful factors of controlling memory and behavior processes. Acute hypoxia exerts a differential impact on different deficits of mnestic and cognitive functions. Instrumental reflexes of active and passive avoidance, negative learning, behavior with a change in the stereotype of learning are more greatly damaged. Memory with spatial and visual differentiation and their rearrangement change to a lesser extent and conditional reflexes are not deranged. In this contract, altitude hypoxic adaptation enhances information fixation and increases the degree and duration of retention of temporary relations. Nootropic agents with an antihypoxic action exert a marked effect on hypoxia-induced cognitive and memory disorders and the magnitude of this effect depends on the ration of proper nootropic to antihypoxic components in the spectrum of the drugs' pharmacological activity. The agents that combine a prevailing antiamnestic effect and a marked and moderate antihypoxic action (mexidole, nooglutil, pyracetam, beglymin, etc.) are most effective in eliminating different hypoxia-induced cognitive and memory disorders, nootropic drugs that have a pronounced antiamnestic activity (centrophenoxine, etc.) and no antihypoxic component also restore the main types of mnestic disorders after hypoxia, but to a lesser extent.

hCG and Its Disruption by Environmental Contaminants during Human Pregnancy

PubMed Central

Paulesu, Luana; Rao, Ch.V.; Ietta, Francesca; Pietropolli, Adalgisa; Ticconi, Carlo

2018-01-01

Human chorionic gonadotropin (hCG) is a hormone of considerable importance in the establishment, promotion and maintenance of human pregnancy. It has been clearly demonstrated that hCG exerts multiple endocrine, paracrine and autocrine actions on a variety of gestational and non-gestational cells and tissues. These actions are directed to promote trophoblast invasiveness and differentiation, placental growth, angiogenesis in uterine vasculature, hormone production, modulation of the immune system at the maternal-fetal interface, inhibition of myometrial contractility as well as fetal growth and differentiation. In recent years, considerable interest has been raised towards the biological effects of environmental contaminants, particularly endocrine disrupting chemicals (EDCs). Emerging evidence suggests that prenatal exposure to selected EDCs can have a deleterious impact on the fetus and long-lasting consequences also in adult life. The results of the in vitro effects of commonly found EDCs, particularly Bisphenol A (BPA) and para-Nonylphenol (p-NP), indicate that these substances can alter hCG production and through this action could exert their fetal damage, suggesting that hCG could represent and become a potentially useful clinical biomarker of an inappropriate prenatal exposure to these substances. PMID:29558393

hCG and Its Disruption by Environmental Contaminants during Human Pregnancy.

PubMed

Paulesu, Luana; Rao, Ch V; Ietta, Francesca; Pietropolli, Adalgisa; Ticconi, Carlo

2018-03-20

Human chorionic gonadotropin (hCG) is a hormone of considerable importance in the establishment, promotion and maintenance of human pregnancy. It has been clearly demonstrated that hCG exerts multiple endocrine, paracrine and autocrine actions on a variety of gestational and non-gestational cells and tissues. These actions are directed to promote trophoblast invasiveness and differentiation, placental growth, angiogenesis in uterine vasculature, hormone production, modulation of the immune system at the maternal-fetal interface, inhibition of myometrial contractility as well as fetal growth and differentiation. In recent years, considerable interest has been raised towards the biological effects of environmental contaminants, particularly endocrine disrupting chemicals (EDCs). Emerging evidence suggests that prenatal exposure to selected EDCs can have a deleterious impact on the fetus and long-lasting consequences also in adult life. The results of the in vitro effects of commonly found EDCs, particularly Bisphenol A (BPA) and para -Nonylphenol ( p -NP), indicate that these substances can alter hCG production and through this action could exert their fetal damage, suggesting that hCG could represent and become a potentially useful clinical biomarker of an inappropriate prenatal exposure to these substances.

Cannabidiol in medical marijuana: Research vistas and potential opportunities.

PubMed

Rong, Carola; Lee, Yena; Carmona, Nicole E; Cha, Danielle S; Ragguett, Renee-Marie; Rosenblat, Joshua D; Mansur, Rodrigo B; Ho, Roger C; McIntyre, Roger S

2017-07-01

The high and increasing prevalence of medical marijuana consumption in the general population invites the need for quality evidence regarding its safety and efficacy. Herein, we synthesize extant literature pertaining to the phytocannabinoid cannabidiol (CBD) and its brain effects. The principle phytocannabinoid Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and CBD are the major pharmacologically active cannabinoids. The effect of CBD on brain systems as well as on phenomenological measures (e.g. cognitive function) are distinct and in many cases opposite to that of Δ 9 -THC. Cannabidiol is without euphoriant properties, and exerts antipsychotic, anxiolytic, anti-seizure, as well as anti-inflammatory properties. It is essential to parcellate phytocannabinoids into their constituent moieties as the most abundant cannabinoid have differential effects on physiologic systems in psychopathology measures. Disparate findings and reports related to effects of cannabis consumption reflect differential relative concentration of Δ 9 -THC and CBD. Existing literature, notwithstanding its deficiencies, provides empirical support for the hypothesis that CBD may exert beneficial effects on brain effector systems/substrates subserving domain-based phenomenology. Interventional studies with purified CBD are warranted with a call to target-engagement proof-of-principle studies using the research domain criteria (RDoC) framework. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modulation of neonatal microbial recognition: TLR-mediated innate immune responses are specifically and differentially modulated by human milk.

PubMed

LeBouder, Emmanuel; Rey-Nores, Julia E; Raby, Anne-Catherine; Affolter, Michael; Vidal, Karine; Thornton, Catherine A; Labéta, Mario O

2006-03-15

The mechanisms controlling innate microbial recognition in the neonatal gut are still to be fully understood. We have sought specific regulatory mechanisms operating in human breast milk relating to TLR-mediated microbial recognition. In this study, we report a specific and differential modulatory effect of early samples (days 1-5) of breast milk on ligand-induced cell stimulation via TLRs. Although a negative modulation was exerted on TLR2 and TLR3-mediated responses, those via TLR4 and TLR5 were enhanced. This effect was observed in human adult and fetal intestinal epithelial cell lines, monocytes, dendritic cells, and PBMC as well as neonatal blood. In the latter case, milk compensated for the low capacity of neonatal plasma to support responses to LPS. Cell stimulation via the IL-1R or TNFR was not modulated by milk. This, together with the differential effect on TLR activation, suggested that the primary effect of milk is exerted upstream of signaling proximal to TLR ligand recognition. The analysis of TLR4-mediated gene expression, used as a model system, showed that milk modulated TLR-related genes differently, including those coding for signal intermediates and regulators. A proteinaceous milk component of > or =80 kDa was found to be responsible for the effect on TLR4. Notably, infant milk formulations did not reproduce the modulatory activity of breast milk. Together, these findings reveal an unrecognized function of human milk, namely, its capacity to influence neonatal microbial recognition by modulating TLR-mediated responses specifically and differentially. This in turn suggests the existence of novel mechanisms regulating TLR activation.

Paramagnetic Beads and Magnetically Mediated Strain Enhance Cardiomyogenesis in Mouse Embryoid Bodies

PubMed Central

Geuss, Laura R.; Wu, Douglas C.; Ramamoorthy, Divya; Alford, Corinne D.; Suggs, Laura J.

2014-01-01

Mechanical forces play an important role in proper embryologic development, and similarly such forces can directly impact pluripotency and differentiation of mouse embryonic stem cells (mESC) in vitro. In addition, manipulation of the embryoid body (EB) microenvironment, such as by incorporation of microspheres or microparticles, can similarly influence fate determination. In this study, we developed a mechanical stimulation regimen using permanent neodymium magnets to magnetically attract cells within an EB. Arginine-Glycine-Aspartic Acid (RGD)-conjugated paramagnetic beads were incorporated into the interior of the EBs during aggregation, allowing us to exert force on individual cells using short-term magnetization. EBs were stimulated for one hour at different magnetic field strengths, subsequently exerting a range of force intensity on the cells at different stages of early EB development. Our results demonstrated that following exposure to a 0.2 Tesla magnetic field, ESCs respond to magnetically mediated strain by activating Protein Kinase A (PKA) and increasing phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) expression. The timing of stimulation can also be tailored to guide ESC differentiation: the combination of bone morphogenetic protein 4 (BMP4) supplementation with one hour of magnetic attraction on Day 3 enhances cardiomyogenesis by increasing contractile activity and the percentage of sarcomeric α-actin-expressing cells compared to control samples with BMP4 alone. Interestingly, we also observed that the beads alone had some impact on differentiation by increasingly slightly, albeit not significantly, the percentage of cardiomyocytes. Together these results suggest that magnetically mediated strain can be used to enhance the percentage of mouse ESC-derived cardiomyocytes over current differentiation protocols. PMID:25501004

Synchronous luminescence spectroscopic characterization of blood elements of normal and patients with cervical cancer

NASA Astrophysics Data System (ADS)

Muthuvelu, K.; Shanmugam, Sivabalan; Koteeswaran, Dornadula; Srinivasan, S.; Venkatesan, P.; Aruna, Prakasarao; Ganesan, Singaravelu

2011-03-01

In this study the diagnostic potential of synchronous luminescence spectroscopy (SLS) technique for the characterization of normal and different pathological condition of cervix viz., moderately differentiated squamous cell carcinoma (MDSCC), poorly differentiated squamous cell carcinoma (PDSCC) and well differentiated squamous cell carcinoma (WDSSC). Synchronous fluorescence spectra were measured for 70 abnormal cases and 30 normal subjects. Characteristic, highly resolved peaks and significant spectral differences between normal and MDSCC, PDSCC and WDSCC cervical blood formed elements were obtained. The synchronous luminescence spectra of formed elements of normal and abnormal cervical cancer patients were subjected to statistical analysis. Synchronous luminescence spectroscopy provides 90% sensitivity and 92.6% specificity.

Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL) Reveals the Sequential Differentiation of Sieve Element-Like Cells.

PubMed

Kondo, Yuki; Nurani, Alif Meem; Saito, Chieko; Ichihashi, Yasunori; Saito, Masato; Yamazaki, Kyoko; Mitsuda, Nobutaka; Ohme-Takagi, Masaru; Fukuda, Hiroo

2016-06-01

Cell differentiation is a complex process involving multiple steps, from initial cell fate specification to final differentiation. Procambial/cambial cells, which act as vascular stem cells, differentiate into both xylem and phloem cells during vascular development. Recent studies have identified regulatory cascades for xylem differentiation. However, the molecular mechanism underlying phloem differentiation is largely unexplored due to technical challenges. Here, we established an ectopic induction system for phloem differentiation named Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL). Our results verified similarities between VISUAL-induced Arabidopsis thaliana phloem cells and in vivo sieve elements. We performed network analysis using transcriptome data with VISUAL to dissect the processes underlying phloem differentiation, eventually identifying a factor involved in the regulation of the master transcription factor gene APL Thus, our culture system opens up new avenues not only for genetic studies of phloem differentiation, but also for future investigations of multidirectional differentiation from vascular stem cells. © 2016 American Society of Plant Biologists. All rights reserved.

Effect of citrus flavonoids on HL-60 cell differentiation.

PubMed

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

1999-01-01

Twenty-seven Citrus flavonoids were examined for their activity of induction of terminal differentiation of human promyelocytic leukemia cells (HL-60) by nitro blue tetrazolium (NBT) reducing, nonspecific esterase, specific esterase, and phagocytic activities. 10 flavonoids were judged to be active (percentage of NBT reducing cells was more than 40% at a concentration of 40 microM), and the rank order of potency was natsudaidain, luteolin, tangeretin, quercetin, apigenin, 3, 3, '4, '5, 6, 7, 8-heptamethoxyflavone, nobiletin, acacetin, eriodictyol, and taxifolin. These flavonoids exerted their activity in a dose-dependent manner. HL-60 cells treated with these flavonoids differentiated into mature monocyte/macrophage. The structure-activity relationship established from comparison between flavones and flavanones revealed that ortho-catechol moiety in ring B and C2-C3 double bond had an important role for induction of differentiation of HL-60. In polymethoxylated flavones, hydroxyl group at C3 and methoxyl group at C8 enhanced the differentiation-inducing activity.

Area-specific temporal control of corticospinal motor neuron differentiation by COUP-TFI

PubMed Central

Tomassy, Giulio Srubek; De Leonibus, Elvira; Jabaudon, Denis; Lodato, Simona; Alfano, Christian; Mele, Andrea; Macklis, Jeffrey D.; Studer, Michèle

2010-01-01

Transcription factors with gradients of expression in neocortical progenitors give rise to distinct motor and sensory cortical areas by controlling the area-specific differentiation of distinct neuronal subtypes. However, the molecular mechanisms underlying this area-restricted control are still unclear. Here, we show that COUP-TFI controls the timing of birth and specification of corticospinal motor neurons (CSMN) in somatosensory cortex via repression of a CSMN differentiation program. Loss of COUP-TFI function causes an area-specific premature generation of neurons with cardinal features of CSMN, which project to subcerebral structures, including the spinal cord. Concurrently, genuine CSMN differentiate imprecisely and do not project beyond the pons, together resulting in impaired skilled motor function in adult mice with cortical COUP-TFI loss-of-function. Our findings indicate that COUP-TFI exerts critical areal and temporal control over the precise differentiation of CSMN during corticogenesis, thereby enabling the area-specific functional features of motor and sensory areas to arise. PMID:20133588

Corticosterone affects the differentiation of a neuronal cerebral cortex-derived cell line through modulation of the nicotinic acetylcholine receptor.

PubMed

Baier, C J; Franco, D L; Gallegos, C E; Mongiat, L A; Dionisio, L; Bouzat, C; Caviedes, P; Barrantes, F J

2014-08-22

Chronic exposure to stress hormones has an impact on brain structures relevant to cognition. Nicotinic acetylcholine receptors (AChRs) are involved in numerous cognitive processes including learning and memory formation. In order to better understand the molecular mechanisms of chronic stress-triggered mental disease, the effect of corticosterone (CORT) on the biology of AChRs was studied in the neuronal cell line CNh. We found that chronic treatment with CORT reduced the expression levels of the α7-type neuronal AChR and, to a lesser extent, of α4-AChR. CORT also delayed the acquisition of the mature cell phenotype in CNh cells. Chronic nicotine treatment affected the differentiation of CNh cells and exerted a synergistic effect with CORT, suggesting that AChR could participate in signaling pathways that control the cell cycle. Overexpression of α7-AChR-GFP abolished the CORT effects on the cell cycle and the specific α7-AChR inhibitor, methyllycaconitine, mimicked the proliferative action exerted by CORT. Whole-cell voltage-clamp recordings showed a significant decrease in nicotine-evoked currents in CORT-treated cells. Taken together, these observations indicate that AChRs, and the α7-AChR in particular, could act as modulators of the differentiation of CNh cells and that CORT could impair the acquisition of a mature phenotype by affecting the function of this AChR subtype. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Esculetin attenuates receptor activator of nuclear factor kappa-B ligand-mediated osteoclast differentiation through c-Fos/nuclear factor of activated T-cells c1 signaling pathway

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

Baek, Jong Min; Park, Sun-Hyang; Cheon, Yoon-Hee

Esculetin exerts various biological effects on anti-oxidation, anti-tumors, and anti-inflammation. However, the involvement of esculetin in the bone metabolism process, particularly osteoclast differentiation has not yet been investigated. In the present study, we first confirmed the inhibitory effect of esculetin on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation. We then revealed the relationship between esculetin and the expression of osteoclast-specific molecules to elucidate its underlying mechanisms. Esculetin interfered with the expression of c-Fos and nuclear factor of activated T cell c1 (NFATc1) both at the mRNA and protein level with no involvement in osteoclast-associated early signaling pathways, suppressingmore » the expression of various transcription factors exclusively expressed in osteoclasts such as tartrate-resistant acid phosphatase (Trap), osteoclast-associated receptor (Oscar), dendritic cell-specific transmembrane protein (Dcstamp), osteoclast stimulatory transmembrane protein (Ocstamp), cathepsin K, αvβ3 integrin, and calcitonin receptor (Ctr). Additionally, esculetin inhibited the formation of filamentous actin (F-actin) ring-positive osteoclasts during osteoclast differentiation. However, the development of F-actin structures and subsequent bone resorbing activity of mature osteoclasts, which are observed in osteoclast/osteoblast co-culture systems were not affected by esculetin. Taken together, our results indicate for the first time that esculetin inhibits RANKL-mediated osteoclastogenesis via direct suppression of c-Fos and NFATc1 expression and exerts an inhibitory effect on actin ring formation during osteoclastogenesis. - Highlights: • We first investigated the effects of esculetin on osteoclast differentiation and function. • Our data demonstrate for the first time that esculetin can suppress osteoclastogenesis in vitro. • Esculetin acts as an inhibitor of c-Fos and NFATc1 activation. • Esculetin acts a negative regulator of actin ring formation during osteoclast differentiation. • Esculetin deserves new evaluation as a potential treatment target in various bone diseases.« less

Regulation of tyrosine hydroxylase gene expression during differentiation of neuroblastoma cells.

PubMed

Summerhill, E M; Wood, K; Fishman, M C

1987-07-01

Differentiation of N1E-115 neuroblastoma cells into neuron-like cells, with extension of neurites and acquisition of excitable membranes, can be induced by dimethyl sulfoxide (DMSO). We have found this differentiation to be accompanied by an increase in tyrosine hydroxylase (TH) mRNA, an increase disproportionate to changes in mRNAs for other measured, non-neuron-specific genes. The mRNA increases slowly over several days and falls gradually after removal of DMSO. Nuclear run-on studies suggest that a change in the rate of transcription cannot explain the increase in steady-state mRNA levels. TH mRNA half-life does, however, increase. This suggests that regulation is exerted in this case not at the level of transcription but rather at that of mRNA stability.

Second level semi-degenerate fields in W_3 Toda theory: matrix element and differential equation

NASA Astrophysics Data System (ADS)

Belavin, Vladimir; Cao, Xiangyu; Estienne, Benoit; Santachiara, Raoul

2017-03-01

In a recent study we considered W_3 Toda 4-point functions that involve matrix elements of a primary field with the highest-weight in the adjoint representation of sl_3 . We generalize this result by considering a semi-degenerate primary field, which has one null vector at level two. We obtain a sixth-order Fuchsian differential equation for the conformal blocks. We discuss the presence of multiplicities, the matrix elements and the fusion rules.

Genome-wide Analysis of the H3K4 Histone Demethylase RBP2 Reveals a Transcriptional Program Controlling Differentiation

PubMed Central

Lopez-Bigas, Nuria; Kisiel, Tomasz A.; DeWaal, Dannielle C.; Holmes, Katie B.; Volkert, Tom L.; Gupta, Sumeet; Love, Jennifer; Murray, Heather L.; Young, Richard A.; Benevolenskaya, Elizaveta V.

2010-01-01

SUMMARY Retinoblastoma protein (pRB) mediates cell-cycle withdrawal and differentiation by interacting with a variety of proteins. RB-Binding Protein 2 (RBP2) has been shown to be a key effector. We sought to determine transcriptional regulation by RBP2 genome-wide by using location analysis and gene expression profiling experiments. We describe that RBP2 shows high correlation with the presence of H3K4me3 and its target genes are separated into two functionally distinct classes: differentiation-independent and differentiation-dependent genes. The former class is enriched by genes that encode mitochondrial proteins, while the latter is represented by cell-cycle genes. We demonstrate the role of RBP2 in mitochondrial biogenesis, which involves regulation of H3K4me3-modified nucleosomes. Analysis of expression changes upon RBP2 depletion depicted genes with a signature of differentiation control, analogous to the changes seen upon reintroduction of pRB. We conclude that, during differentiation, RBP2 exerts inhibitory effects on multiple genes through direct interaction with their promoters. PMID:18722178

Functional screen reveals essential roles of miR-27a/24 in differentiation of embryonic stem cells

PubMed Central

Ma, Yanni; Yao, Nan; Liu, Guang; Dong, Lei; Liu, Yufang; Zhang, Meili; Wang, Fang; Wang, Bin; Wei, Xueju; Dong, He; Wang, Lanlan; Ji, Shaowei; Zhang, Junwu; Wang, Yangming; Huang, Yue; Yu, Jia

2015-01-01

MicroRNAs play important roles in controlling the embryonic stem cell (ESC) state. Although much is known about microRNAs maintaining ESC state, microRNAs that are responsible for promoting ESC differentiation are less reported. Here, by screening 40 microRNAs pre-selected by their expression patterns and predicted targets in Dgcr8-null ESCs, we identify 14 novel differentiation-associated microRNAs. Among them, miR-27a and miR-24, restrained by c-Myc in ESC, exert their roles of silencing self-renewal through directly targeting several important pluripotency-associated factors, such as Oct4, Foxo1 and Smads. CRISPR/Cas9-mediated knockout of all miR-27/24 in ESCs leads to serious deficiency in ESC differentiation in vitro and in vivo. Moreover, depleting of them in mouse embryonic fibroblasts can evidently promote somatic cell reprogramming. Altogether, our findings uncover the essential role of miR-27 and miR-24 in ESC differentiation and also demonstrate novel microRNAs responsible for ESC differentiation. PMID:25519956

Matrix Property-Controlled Stem Cell Differentiation for Cardiac and Skeletal Tissue Regeneration

NASA Astrophysics Data System (ADS)

Xu, Yanyi

When ischemia, caused by diseases such as myocardial infarction (MI) or atherosclerotic peripheral artery disease (PAD), happens in myocardium or skeletal muscles, the depletion of oxygen and nutrients can cause the immediate death of muscle cells, the formation of stiff scar tissues, followed by the mechanical and functional properties loss of heart/skeletal muscles. In order to treat these diseases, it's necessary to: 1). fast re-establish the blood flow of ischemic tissues; 2). fully regenerate the cardiac/skeletal muscles to restore the tissue functions. One of the widely used approaches to reach these treatment goals is stem cell transplantation. By using novel biomaterial-based scaffolds (gels, foams or fibrous networks), stem cells may be delivered into the injured area, differentiate into cardiomyocytes/myofibers and help the regeneration of local tissues. In the first part of this work, physical induction approaches for stem cell differentiation is presented. Using an electrospinning method, fibrous scaffolds based on hydrogel and polyurethane (PU) were fabricated and cardiac differentiation of cardio-sphere derived cells (CDCs) was successfully induced through the control of scaffold mechanical and morphological properties (fiber diameter, density, alignment, single fiber modulus and scaffold macro modulus). In a hydrogel system, the matrix modulus was successfully decoupled from the chemical structure, composition and water content properties, and a matrix tensile modulus of around 20kPa was found to better induce the myogenic differentiation of mesenchymal stem cells (MSCs) cultured under normal condition. In the other hand, due to the harsh local environment caused by ischemia, the transplanted cells usually have low survival and differentiation rates. To solve this problem, cells were delivered in hydrogels with angiogenesis factor basic fibroblast growth factor (bFGF) or oxygen release microspheres (ORM) to conquer the local low oxygen and low nutrient conditions. The second part of this work focuses on the application of this delivery system in vivo using a mice hindlimb ischemia model. Results showed that MSC survival and myogenic differentiation rates were significantly improved both in vitro and in vivo with the delivery of bFGF or ORM under ischemic condition. In addition, a dramatic increase of muscle fiber regeneration, blood flow recovery as well as the mechanical/functional (muscle contractility, fatigue resistance and mice running ability) properties was observed. These results indicate the great potential of this cell-gel-biomolecule system in the treatment of muscle regeneration. To better understand how the matrix modulus affects the stem cell differentiation, we developed a novel approach using digital image correlation (DIC) and finite element modeling (FEM) to calculate the cell-generated tractions. This is presented in the third part of this work, and our results demonstrated that MSCs with higher myogenic differentiation exerted larger tractions to their surrounding matrix.

Combined passive magnetic bearing element and vibration damper

DOEpatents

Post, Richard F.

2001-01-01

A magnetic bearing system contains magnetic subsystems which act together to support a rotating element in a state of dynamic equilibrium and dampen transversely directed vibrations. Mechanical stabilizers are provided to hold the suspended system in equilibrium until its speed has exceeded a low critical speed where dynamic effects take over, permitting the achievement of a stable equilibrium for the rotating object. A state of stable equilibrium is achieved above a critical speed by use of a collection of passive elements using permanent magnets to provide their magnetomotive excitation. In a improvement over U.S. Pat. No. 5,495,221, a magnetic bearing element is combined with a vibration damping element to provide a single upper stationary dual-function element. The magnetic forces exerted by such an element, enhances levitation of the rotating object in equilibrium against external forces, such as the force of gravity or forces arising from accelerations, and suppresses the effects of unbalance or inhibits the onset of whirl-type rotor-dynamic instabilities. Concurrently, this equilibrium is made stable against displacement-dependent drag forces of the rotating object from its equilibrium position.

Adipogenic Effects and Gene Expression Profiling of Firemaster® 550 Components in Human Primary Preadipocytes

PubMed Central

Tung, Emily W.Y.; Peshdary, Vian; Gagné, Remi; Rowan-Carroll, Andrea; Yauk, Carole L.; Boudreau, Adéle

2017-01-01

Background: Exposure to flame retardants has been associated with negative health outcomes including metabolic effects. As polybrominated diphenyl ether flame retardants were pulled from commerce, human exposure to new flame retardants such as Firemaster® 550 (FM550) has increased. Although previous studies in murine systems have shown that FM550 and its main components increase adipogenesis, the effects of FM550 in human models have not been elucidated. Objectives: The objectives of this study were to determine if FM550 and its components are active in human preadipocytes, and to further investigate their mode of action. Methods: Human primary preadipocytes were differentiated in the presence of FM550 and its components. Differentiation was assessed by lipid accumulation and expression of peroxisome proliferator-activated receptor γ (PPARG), fatty acid binding protein (FABP) 4 and lipoprotein lipase (LPL). mRNA was collected for Poly (A) RNA sequencing and was used to identify differentially expressed genes (DEGs). Functional analysis of DEGs was undertaken in Ingenuity Pathway Analysis. Results: FM550 triphenyl phosphate (TPP) and isopropylated triphenyl phosphates (IPTP), increased adipogenesis in human primary preadipocytes as assessed by lipid accumulation and mRNA expression of regulators of adipogenesis such as PPARγ, CCAAT enhancer binding protein (C/EBP) α and sterol regulatory element binding protein (SREBP) 1 as well as the adipogenic markers FABP4 LPL and perilipin. Poly (A) RNA sequencing analysis revealed potential modes of action including liver X receptor/retinoid X receptor (LXR/RXR) activation, thyroid receptor (TR)/RXR, protein kinase A, and nuclear receptor subfamily 1 group H members activation. Conclusions: We found that FM550, and two of its components, induced adipogenesis in human primary preadipocytes. Further, using global gene expression analysis we showed that both TPP and IPTP likely exert their effects through PPARG to induce adipogenesis. In addition, IPTP perturbed signaling pathways that were not affected by TPP. https://doi.org/10.1289/EHP1318 PMID:28934090

Cytological and cytochemical analysis of the effects of hormones on postradiation changes in testicular sex and incretory cells. [. gamma. rays; x rays; mice

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

Kondratenko, V.G.; Ganzenko, L.F.; Stakanov, V.A.

1979-06-01

Cytochemical and cytological analysis demonstrated that administration of testosterone propionate or estradiol propionate alters nuclear nucleoproteins of Leydig and Sertoli cells, as well as spermatogeneic elements. It was shown that the hormones modify the testicular reactions to radiation and, by influencing regulation of spermatogenesis, exert a protective action.

Exploring tree species colonization potentials using a spatially explicit simulation model: implications for four oaks under climate change

Treesearch

Anantha M. Prasad; Judith D. Gardiner; Louis R. Iverson; Stephen N. Matthews; Matthew Peters

2013-01-01

Climate change impacts tree species differentially by exerting unique pressures and altering their suitable habitats. We previously predicted these changes in suitable habitat for current and future climates using a species habitat model (DISTRIB) in the eastern United States. Based on the accuracy of the model, the species assemblages should eventually reflect the new...

Regulatory network involving miRNAs and genes in serous ovarian carcinoma

PubMed Central

Zhao, Haiyan; Xu, Hao; Xue, Luchen

2017-01-01

Serous ovarian carcinoma (SOC) is one of the most life-threatening types of gynecological malignancy, but the pathogenesis of SOC remains unknown. Previous studies have indicated that differentially expressed genes and microRNAs (miRNAs) serve important functions in SOC. However, genes and miRNAs are identified in a disperse form, and limited information is known about the regulatory association between miRNAs and genes in SOC. In the present study, three regulatory networks were hierarchically constructed, including a differentially-expressed network, a related network and a global network to reveal associations between each factor. In each network, there were three types of factors, which were genes, miRNAs and transcription factors that interact with each other. Focus was placed on the differentially-expressed network, in which all genes and miRNAs were differentially expressed and therefore may have affected the development of SOC. Following the comparison and analysis between the three networks, a number of signaling pathways which demonstrated differentially expressed elements were highlighted. Subsequently, the upstream and downstream elements of differentially expressed miRNAs and genes were listed, and a number of key elements (differentially expressed miRNAs, genes and TFs predicted using the P-match method) were analyzed. The differentially expressed network partially illuminated the pathogenesis of SOC. It was hypothesized that if there was no differential expression of miRNAs and genes, SOC may be prevented and treatment may be identified. The present study provided a theoretical foundation for gene therapy for SOC. PMID:29113276

Endothelin-1 expression is strongly repressed by AU-rich elements in the 3′-untranslated region of the gene

PubMed Central

2004-01-01

The regulation of the synthesis of the endothelial-derived vasoconstrictor ET-1 (endothelin-1) is a complex process that occurs mainly at the mRNA level. Transcription of the gene accounts for an important part of the regulation of expression, as already described for different modulators such as the cytokine TGF-β (transforming growth factor-β). However, very little is known about mechanisms governing ET-1 expression at the post-transcriptional level. The aim of the present study was to investigate the regulation of the ET-1 expression at this level. Since the 3′-UTR (3′-untranslated region) of mRNAs commonly contains genetic determinants for the post-transcriptional control of gene expression, we focused on the potential role of the 3′-UTR of ET-1 mRNA. Experiments performed with luciferase reporter constructs containing the 3′-UTR showed that this region exerts a potent destabilizing effect. Deletional analyses allowed us to locate this activity within a region at positions 924–1127. Some (but not all) of the AREs (AU-rich elements) present in this region were found to be essential for this mRNA-destabilizing activity. We also present evidence that cytosolic proteins from endothelial cells interact specifically with these RNA elements, and that a close correlation exists between the ability of the AREs to destabilize ET-1 mRNA and the binding of proteins to these elements. Our results are compatible with the existence of a strong repressional control of ET-1 expression mediated by destabilization of the mRNA exerted through the interaction of specific cytosolic proteins with AREs present in the 3′-UTR of the gene. PMID:15595926

A factor influence study of trace element bioaccumulation in moss bags.

PubMed

Cesa, M; Campisi, B; Bizzotto, A; Ferraro, C; Fumagalli, F; Nimis, P L

2008-10-01

Moss bags of Rhynchostegium riparioides were exposed to different water concentrations of 11 trace elements under laboratory conditions, according to a saturated fractional factorial design (67 treated combinations), with the aim of measuring (1) element uptake and (2) the main effects and first-order interactions of influent factors. Bioaccumulation was directly proportional to water concentration, but the uptake ratio (ranging from 10(2) to 10(5)) also depended on the concentration of other metals. The highest uptake ratios were observed for Al, Cu, Cr, Hg, and Pb. The multiple regression model showed that interactions among elements exist and induce both antagonism (Fe is the most frequent competitor) and synergism (Cr exerts a great influence on Pb and Zn uptake). Interactions might be relatively strong (as for As, Cr, and Pb) or weak (Cd and Hg). This evidence should be taken into consideration in biomonitoring surveys of industrial sites, where effluents release more than one contaminant.

Plant development. Arabidopsis NAC45/86 direct sieve element morphogenesis culminating in enucleation.

PubMed

Furuta, Kaori Miyashima; Yadav, Shri Ram; Lehesranta, Satu; Belevich, Ilya; Miyashima, Shunsuke; Heo, Jung-ok; Vatén, Anne; Lindgren, Ove; De Rybel, Bert; Van Isterdael, Gert; Somervuo, Panu; Lichtenberger, Raffael; Rocha, Raquel; Thitamadee, Siripong; Tähtiharju, Sari; Auvinen, Petri; Beeckman, Tom; Jokitalo, Eija; Helariutta, Ykä

2014-08-22

Photoassimilates such as sugars are transported through phloem sieve element cells in plants. Adapted for effective transport, sieve elements develop as enucleated living cells. We used electron microscope imaging and three-dimensional reconstruction to follow sieve element morphogenesis in Arabidopsis. We show that sieve element differentiation involves enucleation, in which the nuclear contents are released and degraded in the cytoplasm at the same time as other organelles are rearranged and the cytosol is degraded. These cellular reorganizations are orchestrated by the genetically redundant NAC domain-containing transcription factors, NAC45 and NAC86 (NAC45/86). Among the NAC45/86 targets, we identified a family of genes required for enucleation that encode proteins with nuclease domains. Thus, sieve elements differentiate through a specialized autolysis mechanism. Copyright © 2014, American Association for the Advancement of Science.

Catalytic Graphitization of Coal-Based Carbon Materials with Light Rare Earth Elements.

PubMed

Wang, Rongyan; Lu, Guimin; Qiao, Wenming; Yu, Jianguo

2016-08-30

The catalytic graphitization mechanism of coal-based carbon materials with light rare earth elements was investigated using X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray spectroscopy, selected-area electron diffraction, and high-resolution transmission electron microscopy. The interface between light rare earth elements and carbon materials was carefully observed, and two routes of rare earth elements catalyzing the carbon materials were found: dissolution-precipitation and carbide formation-decomposition. These two simultaneous processes certainly accelerate the catalytic graphitization of carbon materials, and light rare earth elements exert significant influence on the microstructure and thermal conductivity of graphite. Moreover, by virtue of praseodymium (Pr), it was found that a highly crystallographic orientation of graphite was induced and formed, which was reasonably attributed to the similar arrangements of the planes perpendicular to (001) in both graphite and Pr crystals. The interface between Pr and carbon was found to be an important factor for the orientation of graphite structure.

A Study on the Relationship between Design Elements of Outdoor Leisure Spaces and Types of Leisure Activities in Sustainable Community Development - A Case Study on Tainan, Taiwan

NASA Astrophysics Data System (ADS)

Chang, J. H.; Zhang, H.

2018-01-01

Sustainable community development encompasses three aspects: “Lifestyle”, “Production” and “Ecology”. Among them, “Lifestyle” is closest to people and reflects basic human needs. Creating outdoor spaces that encourage residents to engage in leisure activities will not only provide them with spiritual sustenance but also fulfil one of the key criteria in sustainable community development. This study explores the relationship between design elements of outdoor leisure spaces and types of leisure activities from residents' perspective with the goal to inform future spatial planning. The study collected 365 valid questionnaires from Tainan residents. Factor analysis was used to extract factors from design elements of outdoor leisure spaces, and regression analysis was applied to understand the effect level. The result shows design elements have positive effect on the types of leisure activities. In addition, different elements exert different influences on the choice of activities.

Method of pedestal and common-mode noise correction for switched-capacitor analog memories

DOEpatents

Britton, Charles L.

1997-01-01

A method and apparatus for correcting common-mode noise and pedestal noise in a multichannel array of switched-capacitor analog memories wherein each analog memory is connected to an associated analog-to-digital converter. The apparatus comprises a single differential element in two different embodiments. In a first embodiment, the differential element is a reference analog memory connected to a buffer. In the second embodiment, the differential dement is a reference analog memory connected to a reference analog-to-digital connected to an array of digital summing circuits.

Origin of Volatiles in Earth: Indigenous Versus Exogenous Sources Based on Highly Siderophile, Volatile Siderophile, and Light Volatile Elements

NASA Technical Reports Server (NTRS)

Righter, K.; Danielson, L.; Pando, K. M.; Marin, N.; Nickodem, K.

2015-01-01

Origin of Earth's volatiles has traditionally been ascribed to late accretion of material after major differentiation events - chondrites, comets, ice or other exogenous sources. A competing theory is that the Earth accreted its volatiles as it was built, thus water and other building blocks were present early and during differentiation and core formation (indigenous). Here we discuss geochemical evidence from three groups of elements that suggests Earth's volatiles were acquired during accretion and did not require additional sources after differentiation.

Identification of Differential Item Functioning in Multiple-Group Settings: A Multivariate Outlier Detection Approach

ERIC Educational Resources Information Center

Magis, David; De Boeck, Paul

2011-01-01

We focus on the identification of differential item functioning (DIF) when more than two groups of examinees are considered. We propose to consider items as elements of a multivariate space, where DIF items are outlying elements. Following this approach, the situation of multiple groups is a quite natural case. A robust statistics technique is…

Differential analysis for the turbulent boundary layer on a compressor blade element (including boundary-layer separation)

NASA Technical Reports Server (NTRS)

Schmidt, J. F.; Todd, C. A.

1974-01-01

A two-dimensional differential analysis is developed to approximate the turbulent boundary layer on a compressor blade element with strong adverse pressure gradients, including the separated region with reverse flow. The predicted turbulent boundary layer thicknesses and velocity profiles are in good agreement with experimental data for a cascade blade, even in the separated region.

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

PubMed Central

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

2016-01-01

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

Boron nitride nanotube-enhanced osteogenic differentiation of mesenchymal stem cells.

PubMed

Li, Xia; Wang, Xiupeng; Jiang, Xiangfen; Yamaguchi, Maho; Ito, Atsuo; Bando, Yoshio; Golberg, Dmitri

2016-02-01

The interaction between boron nitride nanotubes (BNNTs) layer and mesenchymal stem cells (MSCs) is evaluated for the first time in this study. BNNTs layer supports the attachment and growth of MSCs and exhibits good biocompatibility with MSCs. BNNTs show high protein adsorption ability, promote the proliferation of MSCs and increase the secretion of total protein by MSCs. Especially, BNNTs enhance the alkaline phosphatase (ALP) activity as an early marker of osteoblasts, ALP/total protein and osteocalcin (OCN) as a late marker of osteogenic differentiation, which shows that BNNTs can enhance osteogenesis of MSCs. The release of trace boron and the stress on cells exerted by BNNTs with a fiber structure may account for the enhanced differentiation of MSCs into osteoblasts. Therefore BNNTs are potentially useful for bone regeneration in orthopedic applications. © 2015 Wiley Periodicals, Inc.

Comparison of force exerted on the sternum during a sneeze versus during low-, moderate-, and high-intensity bench press resistance exercise with and without the valsalva maneuver in healthy volunteers.

PubMed

Adams, Jenny; Schmid, Jack; Parker, Robert D; Coast, J Richard; Cheng, Dunlei; Killian, Aaron D; McCray, Stephanie; Strauss, Danielle; McLeroy Dejong, Sandra; Berbarie, Rafic

2014-03-15

Sternal precautions are intended to prevent complications after median sternotomy, but little data exist to support the consensus recommendations. To better characterize the forces on the sternum that can occur during everyday events, we conducted a prospective nonrandomized study of 41 healthy volunteers that evaluated the force exerted during bench press resistance exercise and while sneezing. A balloon-tipped esophageal catheter, inserted through the subject's nose and advanced into the thoracic cavity, was used to measure the intrathoracic pressure differential during the study activities. After the 1 repetition maximum (1-RM) was assessed, the subject performed the bench press at the following intensities, first with controlled breathing and then with the Valsalva maneuver: 40% of 1-RM (low), 70% of 1-RM (moderate), and 1-RM (high). Next, various nasal irritants were used to induce a sneeze. The forces on the sternum were calculated according to a cylindrical model, and a 2-tailed paired t test was used to compare the mean force exerted during a sneeze with the mean force exerted during each of the 6 bench press exercises. No statistically significant difference was found between the mean force from a sneeze (41.0 kg) and the mean total force exerted during moderate-intensity bench press exercise with breathing (41.4 kg). In conclusion, current guidelines and recommendations limit patient activity after a median sternotomy. Because these patients can repeatedly withstand a sneeze, our study indicates that they can withstand the forces from more strenuous activities than are currently allowed. Copyright © 2014 Elsevier Inc. All rights reserved.

A meshless EFG-based algorithm for 3D deformable modeling of soft tissue in real-time.

PubMed

Abdi, Elahe; Farahmand, Farzam; Durali, Mohammad

2012-01-01

The meshless element-free Galerkin method was generalized and an algorithm was developed for 3D dynamic modeling of deformable bodies in real time. The efficacy of the algorithm was investigated in a 3D linear viscoelastic model of human spleen subjected to a time-varying compressive force exerted by a surgical grasper. The model remained stable in spite of the considerably large deformations occurred. There was a good agreement between the results and those of an equivalent finite element model. The computational cost, however, was much lower, enabling the proposed algorithm to be effectively used in real-time applications.

Differential maneuvering simulator data reduction and analysis software

NASA Technical Reports Server (NTRS)

Beasley, G. P.; Sigman, R. S.

1972-01-01

A multielement data reduction and analysis software package has been developed for use with the Langley differential maneuvering simulator (DMS). This package, which has several independent elements, was developed to support all phases of DMS aircraft simulation studies with a variety of both graphical and tabular information. The overall software package is considered unique because of the number, diversity, and sophistication of the element programs available for use in a single study. The purpose of this paper is to discuss the overall DMS data reduction and analysis package by reviewing the development of the various elements of the software, showing typical results that can be obtained, and discussing how each element can be used.

Power Experienced by Women as Described by Chief Academic Officers at Women's Colleges and Universities in the United States

ERIC Educational Resources Information Center

Dustrud, Stephanine A. Martin

2012-01-01

Power is embedded within all aspects of human experience and has been a fundamental constituent in social systems since the beginning of recorded history. Power exists in every organization and evolves as the culture of the organization exerts its influence. Organizational structures and systems dictate the elements of power, its use, and its…

Modelling the maximum voluntary joint torque/angular velocity relationship in human movement.

PubMed

Yeadon, Maurice R; King, Mark A; Wilson, Cassie

2006-01-01

The force exerted by a muscle is a function of the activation level and the maximum (tetanic) muscle force. In "maximum" voluntary knee extensions muscle activation is lower for eccentric muscle velocities than for concentric velocities. The aim of this study was to model this "differential activation" in order to calculate the maximum voluntary knee extensor torque as a function of knee angular velocity. Torque data were collected on two subjects during maximal eccentric-concentric knee extensions using an isovelocity dynamometer with crank angular velocities ranging from 50 to 450 degrees s(-1). The theoretical tetanic torque/angular velocity relationship was modelled using a four parameter function comprising two rectangular hyperbolas while the activation/angular velocity relationship was modelled using a three parameter function that rose from submaximal activation for eccentric velocities to full activation for high concentric velocities. The product of these two functions gave a seven parameter function which was fitted to the joint torque/angular velocity data, giving unbiased root mean square differences of 1.9% and 3.3% of the maximum torques achieved. Differential activation accounts for the non-hyperbolic behaviour of the torque/angular velocity data for low concentric velocities. The maximum voluntary knee extensor torque that can be exerted may be modelled accurately as the product of functions defining the maximum torque and the maximum voluntary activation level. Failure to include differential activation considerations when modelling maximal movements will lead to errors in the estimation of joint torque in the eccentric phase and low velocity concentric phase.

ALK and TGF-Beta Resistance in Breast Cancer

DTIC Science & Technology

2016-10-01

ALK) activates Stat3 and protects hematopoietic cells from cell death. Oncogene, 2002. 21(7): p. 1038 -47. 10 . Khoury, J.D., et al., Differential...of Medicine Houston, TX 77030 9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10 . SPONSOR/MONITOR’S ACRONYM(S) 11. SPONSOR/MONITOR’S REPORT... 10 3 INTRODUCTION: TGF-β exerts its tumor suppressing function by inhibiting the growth of normal epithelial cells. Loss of the

Multi-effects of Resveratrol on stem cell characteristics: Effective dose, time, cell culture conditions and cell type-specific responses of stem cells to Resveratrol.

PubMed

Safaeinejad, Zahra; Kazeminasab, Fatemeh; Kiani-Esfahani, Abbas; Ghaedi, Kamran; Nasr-Esfahani, Mohammad Hossein

2018-06-18

Stem cells which defined by dual features of self-renewal and differentiation potential provide a unique source for repairing damaged tissues to treat a wide spectrum of diseases and injuries. Several recent studies suggest that Resveratrol (RSV), a natural polyphenol component, possesses the ability to improve either culture conditions of stem cells or their target differentiation in culture. This review covers the literature that deals with the effects of RSV and its underlying mechanisms on survival, self-renewal and lineage commitment of various stem cells. Concentration of RSV and duration of treatment with this component could exert differential effects on cellular differentiation processes and cell fate. Therefore, RSV could be accounted as an effective small molecule for a variety of cell therapies which should be implemented by a special care considering, effective concentration and duration of exposure. Copyright © 2018. Published by Elsevier Masson SAS.

Seed predators exert selection on the subindividual variation of seed size.

PubMed

Sobral, M; Guitián, J; Guitián, P; Larrinaga, A R

2014-07-01

Subindividual variation among repeated organs in plants constitutes an overlooked level of variation in phenotypic selection studies, despite being a major component of phenotypic variation. Animals that interact with plants could be selective agents on subindividual variation. This study examines selective pressures exerted during post-dispersal seed predation and germination on the subindividual variation of seed size in hawthorn (Crataegus monogyna). With a seed offering experiment and a germination test, we estimated phenotypic selection differentials for average and subindividual variation of seed size due to seed predation and germination. Seed size affects germination, growth rate and the probability of an individual seed of escaping predation. Longer seeds showed higher germination rates, but this did not result in significant selection on phenotypes of the maternal trees. On the other hand, seed predators avoided wider seeds, and by doing so exerted phenotypic selection on adult average and subindividual variation of seed size. The detected selection on subindividual variation suggests that the levels of phenotypic variation within individual plants may be, at least partly, the adaptive consequence of animal-mediated selection. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

Effects of retinoic acids on the dendritic morphology of cultured hippocampal neurons.

PubMed

Liu, Ying; Kagechika, Hiroyuki; Ishikawa, Junko; Hirano, Hitoshi; Matsukuma, Satoshi; Tanaka, Kazuko; Nakamura, Shoji

2008-08-01

Vitamin A-derived retinoic acids (RAs) are known to exert a variety of biological actions, including modulatory effects on cell differentiation and apoptosis. A recent study has demonstrated that 13-cis-RA and all-trans-RA suppressed neurogenesis in the dentate gyrus of the hippocampus in adult mice. The present experiments were performed to see whether 13-cis-RA and all-trans-RA could alter the dendritic morphology of cultured hippocampal neurons via RA receptors: retinoic acid receptor (RAR) and retinoid X receptor (RXR). High doses of 13-cis-RA and all-trans-RA exerted a negative effect on the cultured hippocampal neurons, while a low dose of 13-cis-RA but not all-trans-RA caused a positive effect. The negative changes induced by 13-cis-RA and all-trans-RA were antagonized by RXR antagonists and RAR antagonists, respectively. The positive changes induced by a low dose of 13-cis-RA were blocked by both RXR antagonists and RAR antagonists. These results suggest that RAs at high concentrations cause a negative effect on the dendritic morphology of cultured hippocampal neurons through RA receptors, while RAs at low concentrations exert a positive influence on cultured hippocampal neurons.

Advances on microRNA in regulating mammalian skeletal muscle development.

PubMed

Li, Xin-Yun; Fu, Liang-Liang; Cheng, Hui-Jun; Zhao, Shu-Hong

2017-11-20

MicroRNA (miRNA) is a class of short non-coding RNA, which is about 22 bp in length. In mammals, miRNA exerts its funtion through binding with the 3°-UTR region of target genes and inhibiting their translation. Skeletal muscle development is a complex event, including: proliferation, migration and differentiation of skeletal muscle stem cells; proliferation, differentiation and fusion of myocytes; as well as hypertrophy, energy metabolism and conversion of muscle fiber types. The miRNA plays important roles in all processes of skeletal muscle development through targeting the key factors of different stages. Herein we summarize the miRNA related to muscle development, providing a better understanding of the skeletal muscle development.

The immunomodulatory effects of interferon-gamma on mature B-lymphocyte responses.

PubMed

Jurado, A; Carballido, J; Griffel, H; Hochkeppel, H K; Wetzel, G D

1989-06-15

Interferon-gamma (IFN-gamma) exerts a broad spectrum of activities which affect the responses of mature B-cells. It strongly inhibits B-cell activation, acts as a B-cell growth factor (BCGF), and also induces final differentiation to immunoglobulin (Ig) production. IFN-gamma is deeply involved in the differential control of isotype expression, as it enhances IgG2a production and suppresses both IgG1 and IgE production. Although it is now possible to draw a general scheme of the effects of IFN-gamma on B-cells, a number of paradoxical results still exist in the field. In this manuscript, different experimental systems are analyzed in an attempt to explain these apparent paradoxes.

The role of hesperetin on osteogenesis of human mesenchymal stem cells and its function in bone regeneration.

PubMed

Xue, Deting; Chen, Erman; Zhang, Wei; Gao, Xiang; Wang, Shengdong; Zheng, Qiang; Pan, Zhijun; Li, Hang; Liu, Ling

2017-03-28

Hesperetin has been suggested to be involved in bone strength. We aimed to investigate the effects of hesperetin on the osteogenic differentiation of human mesenchymal stem cells and its related mechanisms. We showed that hesperetin promoted osteogenic differentiation of human mesenchymal stem cells in vitro. It potentially exerts its effects via the ERK and Smad signaling pathways. Using a rat osteotomy model, we showed that human mesenchymal stem cells combined with a hesperetin/gelatin sponge scaffold resulted in accelerated fracture healing in vivo. Due to the low cost of hesperetin, it could be used as a growth factor for bone tissue engineering or surgical fracture treatment.

Mineralogical characteristics of sediments and heavy metal mobilization along a river watershed affected by acid mine drainage.

PubMed

Xie, Yingying; Lu, Guining; Yang, Chengfang; Qu, Lu; Chen, Meiqin; Guo, Chuling; Dang, Zhi

2018-01-01

Trace-element concentrations in acid mine drainage (AMD) are primarily controlled by the mineralogy at the sediment-water interface. Results are presented for a combined geochemical and mineralogical survey of Dabaoshan Mine, South China. Developed sequential extraction experiments with the analysis of the main mineralogical phases by semi-quantitative XRD, differential X-ray diffraction (DXRD) and scanning electron microscopy (SEM) were conducted to identify the quantitative relationship between iron minerals and heavy metals. Results showed that schwertmannite, jarosite, goethite and ferrihydrite were the dominant Fe-oxyhydroxide minerals which were detected alternately in the surface sediment with the increasing pH from 2.50 to 6.93 along the Hengshi River. Decreasing contents of schwertmannite ranging from 35 wt % to 6.5 wt % were detected along the Hengshi River, which was corresponding to the decreasing metal contents. The easily reducible fractions exert higher affinity of metals while compared with reducible and relatively stable minerals. A qualitative analysis of heavy metals extracted from the sediments indicated that the retention ability varied: Pb > Mn > Zn > As ≈ Cu > Cr > Cd ≈ Ni. Results in this study are avail for understanding the fate and transport of heavy metals associated with iron minerals and establishing the remediation strategies of AMD systems.

Mineralogical characteristics of sediments and heavy metal mobilization along a river watershed affected by acid mine drainage

PubMed Central

Xie, Yingying; Yang, Chengfang; Qu, Lu; Chen, Meiqin; Guo, Chuling; Dang, Zhi

2018-01-01

Trace-element concentrations in acid mine drainage (AMD) are primarily controlled by the mineralogy at the sediment-water interface. Results are presented for a combined geochemical and mineralogical survey of Dabaoshan Mine, South China. Developed sequential extraction experiments with the analysis of the main mineralogical phases by semi-quantitative XRD, differential X-ray diffraction (DXRD) and scanning electron microscopy (SEM) were conducted to identify the quantitative relationship between iron minerals and heavy metals. Results showed that schwertmannite, jarosite, goethite and ferrihydrite were the dominant Fe-oxyhydroxide minerals which were detected alternately in the surface sediment with the increasing pH from 2.50 to 6.93 along the Hengshi River. Decreasing contents of schwertmannite ranging from 35 wt % to 6.5 wt % were detected along the Hengshi River, which was corresponding to the decreasing metal contents. The easily reducible fractions exert higher affinity of metals while compared with reducible and relatively stable minerals. A qualitative analysis of heavy metals extracted from the sediments indicated that the retention ability varied: Pb > Mn > Zn > As ≈ Cu > Cr > Cd ≈ Ni. Results in this study are avail for understanding the fate and transport of heavy metals associated with iron minerals and establishing the remediation strategies of AMD systems. PMID:29304091

The POU Transcription Factor Oct-1 Represses Virus-Induced Interferon A Gene Expression

PubMed Central

Mesplède, Thibault; Island, Marie-Laure; Christeff, Nicolas; Petek, Fahrettin; Doly, Janine; Navarro, Sébastien

2005-01-01

Alpha interferon (IFN-α) and IFN-β are able to interfere with viral infection. They exert a vast array of biologic functions, including growth arrest, cell differentiation, and immune system regulation. This regulation extends from innate immunity to cellular and humoral adaptive immune responses. A strict control of expression is needed to prevent detrimental effects of unregulated IFN. Multiple IFN-A subtypes are coordinately induced in human and mouse cells infected by virus and exhibit differences in expression of their individual mRNAs. We demonstrated that the weakly expressed IFN-A11 gene is negatively regulated after viral infection, due to a distal negative regulatory element, binding homeoprotein pituitary homeobox 1 (Pitx1). Here we show that the POU protein Oct-1 binds in vitro and in vivo to the IFN-A11 promoter and represses IFN-A expression upon interferon regulatory factor overexpression. Furthermore, we show that Oct-1-deficient MEFs exhibit increased in vivo IFN-A gene expression and increased antiviral activity. Finally, the IFN-A expression pattern is modified in Oct-1-deficient MEFs. The broad representation of effective and potent octamer-like sequences within IFN-A promoters suggests an important role for Oct-1 in IFN-A regulation. PMID:16166650

DNA Microarray Profiling Highlights Nrf2-Mediated Chemoprevention Targeted by Wasabi-Derived Isothiocyanates in HepG2 Cells.

PubMed

Trio, Phoebe Zapanta; Kawahara, Atsuyoshi; Tanigawa, Shunsuke; Sakao, Kozue; Hou, De-Xing

2017-01-01

6-MSITC and 6-MTITC are sulforaphane (SFN) analogs found in Japanese Wasabi. As we reported previously, Wasabi isothiocyanates (ITCs) are activators of Nrf2-antioxidant response element pathway, and also inhibitors of pro-inflammatory cyclooxygenase-2. This study is the first to assess the global changes in transcript levels by Wasabi ITCs, comparing with SFN, in HepG2 cells. We performed comparative gene expression profiling by treating HepG2 cells with ITCs, followed by DNA microarray analyses using HG-U133 plus 2.0 oligonucleotide array. Partial array data on selected gene products were confirmed by RT-PCR and Western blotting. Ingenuity Pathway Analysis (IPA) was used to identify functional subsets of genes and biologically significant network pathways. 6-MTITC showed the highest number of differentially altered (≥2 folds) gene expression, of which 114 genes were upregulated and 75 were downregulated. IPA revealed that Nrf2-mediated pathway, together with glutamate metabolism, is the common significantly modulated pathway across treatments. Interestingly, 6-MSITC exhibited the most potent effect toward Nrf2-mediated pathway. Our data suggest that 6-MSITC could exert chemopreventive role against cancer through its underlying antioxidant activity via the activation of Nrf2-mediated subsequent induction of cytoprotective genes.

Good, Bad, or Ugly: the Biological Roles of Bone Marrow Fat.

PubMed

Singh, Lakshman; Tyagi, Sonia; Myers, Damian; Duque, Gustavo

2018-04-01

Bone marrow fat expresses mixed characteristics, which could correspond to white, brown, and beige types of fat. Marrow fat could act as either energy storing and adipokine secreting white fat or as a source of energy for hematopoiesis and bone metabolism, thus acting as brown fat. However, there is also a negative interaction between marrow fat and other elements of the bone marrow milieu, which is known as lipotoxicity. In this review, we will describe the good and bad roles of marrow fat in the bone, while focusing on the specific components of the negative effect of marrow fat on bone metabolism. Lipotoxicity in the bone is exerted by bone marrow fat through the secretion of adipokines and free fatty acids (FFA) (predominantly palmitate). High levels of FFA found in the bone marrow of aged and osteoporotic bone are associated with decreased osteoblastogenesis and bone formation, decreased hematopoiesis, and increased osteoclastogenesis. In addition, FFA such as palmitate and stearate induce apoptosis and dysfunctional autophagy in the osteoblasts, thus affecting their differentiation and function. Regulation of marrow fat could become a therapeutic target for osteoporosis. Inhibition of the synthesis of FFA by marrow fat could facilitate osteoblastogenesis and bone formation while affecting osteoclastogenesis. However, further studies testing this hypothesis are still required.

Phenolic acid intake, delivered via moderate champagne wine consumption, improves spatial working memory via the modulation of hippocampal and cortical protein expression/activation.

PubMed

Corona, Giulia; Vauzour, David; Hercelin, Justine; Williams, Claire M; Spencer, Jeremy P E

2013-11-10

While much data exist for the effects of flavonoid-rich foods on spatial memory in rodents, there are no such data for foods/beverages predominantly containing hydroxycinnamates and phenolic acids. To address this, we investigated the effects of moderate Champagne wine intake, which is rich in these components, on spatial memory and related mechanisms relative to the alcohol- and energy-matched controls. In contrast to the isocaloric and alcohol-matched controls, supplementation with Champagne wine (1.78 ml/kg BW, alcohol 12.5% vol.) for 6 weeks led to an improvement in spatial working memory in aged rodents. Targeted protein arrays indicated that these behavioral effects were paralleled by the differential expression of a number of hippocampal and cortical proteins (relative to the isocaloric control group), including those involved in signal transduction, neuroplasticity, apoptosis, and cell cycle regulation. Western immunoblotting confirmed the differential modulation of brain-derived neurotrophic factor, cAMP response-element-binding protein (CREB), p38, dystrophin, 2',3'-cyclic-nucleotide 3'-phosphodiesterase, mammalian target of rapamycin (mTOR), and Bcl-xL in response to Champagne supplementation compared to the control drink, and the modulation of mTOR, Bcl-xL, and CREB in response to alcohol supplementation. Our data suggest that smaller phenolics such as gallic acid, protocatechuic acid, tyrosol, caftaric acid, and caffeic acid, in addition to flavonoids, are capable of exerting improvements in spatial memory via the modulation in hippocampal signaling and protein expression. Changes in spatial working memory induced by the Champagne supplementation are linked to the effects of absorbed phenolics on cytoskeletal proteins, neurotrophin expression, and the effects of alcohol on the regulation of apoptotic events in the hippocampus and cortex.

Skn-1a/Oct-11 and {Delta}Np63{alpha} exert antagonizing effects on human keratin expression

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

Lena, Anna Maria; Cipollone, Rita; Amelio, Ivano

2010-10-29

Research highlights: {yields} Skn-1a markedly downregulates {Delta}Np63-driven K14 expression. {yields} {Delta}Np63 inhibits Skn-1a-mediated K10 expression. {yields} {Delta}Np63, mutated in SAM domain, is less effecting in K10 downregulation. {yields} Immunolocalization in human skin of the two transcription factors is partially overlapping. {yields} The antagonistic effects of Skn-1a and p63 is through competition for overlapping responsive elements or through an indirect interaction. -- Abstract: The formation of a stratified epidermis requires a carefully controlled balance between keratinocyte proliferation and differentiation. Here, we report the reciprocal effect on keratin expression of {Delta}Np63, pivotal in normal epidermal morphogenesis and maintenance, and Skn-1a/Oct-11, a POUmore » transcription factor that triggers and regulates the differentiation of keratinocytes. The expression of Skn-1a markedly downregulated {Delta}Np63-driven K14 expression in luciferase reporter assays. The extent of downregulation was comparable to the inhibition of Skn-1a-mediated K10 expression upon expression of {Delta}Np63. {Delta}Np63, mutated in the protein-protein interaction domain (SAM domain; mutated in human ectodermal dysplasia syndrome), was significantly less effecting in downregulating K10, raising the possibility of a direct interaction among Skn-1a and {Delta}Np63. Immunolocalization in human skin biopsies revealed that the expression of the two transcription factors is partially overlapping. Co-immunoprecipitation experiments did not, however, demonstrate a direct interaction between {Delta}Np63 and Skn-1a, suggesting that the antagonistic effects of Skn-1a and p63 on keratin promoter transactivation is probably through competition for overlapping binding sites on target gene promoter or through an indirect interaction.« less

Motivated to do well: an examination of the relationships between motivation, effort, and cognitive performance in schizophrenia.

PubMed

Foussias, G; Siddiqui, I; Fervaha, G; Mann, S; McDonald, K; Agid, O; Zakzanis, K K; Remington, G

2015-08-01

The uncertain relationship between negative symptoms, and specifically motivational deficits, with cognitive dysfunction in schizophrenia is in need of further elucidation as it pertains to the interpretation of cognitive test results. Findings to date have suggested a possible mediating role of motivational deficits on cognitive test measures, although findings from formal examinations of effort using performance validity measures have been inconsistent. The aim of this study was to examine the relationships between motivation, effort exerted during cognitive testing, and cognitive performance in schizophrenia. Sixty-nine outpatients with schizophrenia or schizoaffective disorder were evaluated for psychopathology, severity of motivational deficits, effort exerted during cognitive testing, and cognitive performance. Motivation and degree of effort exerted during cognitive testing were significantly related to cognitive performance, specifically verbal fluency, verbal and working memory, attention and processing speed, and reasoning and problem solving. Further, effort accounted for 15% of the variance in cognitive performance, and partially mediated the relationship between motivation and cognitive performance. Examining cognitive performance profiles for individuals exerting normal or reduced effort revealed significant differences in global cognition, as well as attention/processing speed and reasoning and problem solving. These findings suggest that cognitive domains may be differentially affected by impairments in motivation and effort, and highlight the importance of understanding the interplay between motivation and cognitive performance deficits, which may guide the appropriate selection of symptom targets for promoting recovery in patients. Copyright © 2015 Elsevier B.V. All rights reserved.

Iterative methods for elliptic finite element equations on general meshes

NASA Technical Reports Server (NTRS)

Nicolaides, R. A.; Choudhury, Shenaz

1986-01-01

Iterative methods for arbitrary mesh discretizations of elliptic partial differential equations are surveyed. The methods discussed are preconditioned conjugate gradients, algebraic multigrid, deflated conjugate gradients, an element-by-element techniques, and domain decomposition. Computational results are included.

Method of pedestal and common-mode noise correction for switched-capacitor analog memories

DOEpatents

Britton, C.L.

1997-09-23

A method and apparatus are disclosed for correcting common-mode noise and pedestal noise in a multichannel array of switched-capacitor analog memories wherein each analog memory is connected to an associated analog-to-digital converter. The apparatus comprises a single differential element in two different embodiments. In a first embodiment, the differential element is a reference analog memory connected to a buffer. In the second embodiment, the differential dement is a reference analog memory connected to a reference analog-to-digital connected to an array of digital summing circuits. 4 figs.

Elemental profiling and geographical differentiation of Ethiopian coffee samples through inductively coupled plasma-optical emission spectroscopy (ICP-OES), ICP-mass spectrometry (ICP-MS) and direct mercury analyzer (DMA).

PubMed

Habte, Girum; Hwang, In Min; Kim, Jae Sung; Hong, Joon Ho; Hong, Young Sin; Choi, Ji Yeon; Nho, Eun Yeong; Jamila, Nargis; Khan, Naeem; Kim, Kyong Su

2016-12-01

This study was aimed to establish the elemental profiling and provenance of coffee samples collected from eleven major coffee producing regions of Ethiopia. A total of 129 samples were analyzed for forty-five elements using inductively coupled plasma (ICP)-optical emission spectroscopy (OES), ICP-mass spectrometry (MS) and direct mercury analyzer (DMA). Among the macro elements, K showed the highest levels whereas Fe was found to have the lowest concentration values. In all the samples, Ca, K, Mg, P and S contents were statistically significant (p<0.05). Micro elements showed the concentrations order of: Mn>Cu>Sr>Zn>Rb>Ni>B. Contents of the trace elements were lower than the permissible standard values. Inter-regions differentiation by cluster analysis (CA), linear discriminant analysis (LDA) and principal component analysis (PCA) showed that micro and trace elements are the best chemical descriptors of the analyzed coffee samples. Copyright © 2016 Elsevier Ltd. All rights reserved.

Secreted Clusterin protein inhibits osteoblast differentiation of bone marrow mesenchymal stem cells by suppressing ERK1/2 signaling pathway.

PubMed

Abdallah, Basem M; Alzahrani, Abdullah M; Kassem, Moustapha

2018-05-01

Secreted Clusterin (sCLU, also known as Apolipoprotein J) is an anti-apoptotic glycoprotein involved in the regulation of cell proliferation, lipid transport, extracellular tissue remodeling and apoptosis. sCLU is expressed and secreted by mouse bone marrow-derived skeletal (stromal or mesenchymal) stem cells (mBMSCs), but its functional role in MSC biology is not known. In this study, we demonstrated that Clusterin mRNA expression and protein secretion in conditioned medium increased during adipocyte differentiation and decreased during osteoblast differentiation of mBMSCs. Treatment of mBMSC cultures with recombinant sCLU protein increased cell proliferation and exerted an inhibitory effect on the osteoblast differentiation while stimulated adipocyte differentiation in a dose-dependent manner. siRNA-mediated silencing of Clu expression in mBMSCs reduced adipocyte differentiation and stimulated osteoblast differentiation of mBMSCs. Furthermore, the inhibitory effect of sCLU on the osteoblast differentiation of mBMSCs was mediated by the suppression of extracellular signal-regulated kinase (ERK1/2) phosphorylation. In conclusion, we identified sCLU as a regulator of mBMSCs lineage commitment to osteoblasts versus adipocytes through a mechanism mediated by ERK1/2 signaling. Inhibiting sCLU is a possible therapeutic approach for enhancing osteoblast differentiation and consequently bone formation. Copyright © 2018 Elsevier Inc. All rights reserved.

Evolution of plant conducting cells: perspectives from key regulators of vascular cell differentiation.

PubMed

Ohtani, Misato; Akiyoshi, Nobuhiro; Takenaka, Yuto; Sano, Ryosuke; Demura, Taku

2017-01-01

One crucial problem that plants faced during their evolution, particularly during the transition to growth on land, was how to transport water, nutrients, metabolites, and small signaling molecules within a large, multicellular body. As a solution to this problem, land plants developed specific tissues for conducting molecules, called water-conducting cells (WCCs) and food-conducting cells (FCCs). The well-developed WCCs and FCCs in extant plants are the tracheary elements and sieve elements, respectively, which are found in vascular plants. Recent molecular genetic studies revealed that transcriptional networks regulate the differentiation of tracheary and sieve elements, and that the networks governing WCC differentiation are largely conserved among land plant species. In this review, we discuss the molecular evolution of plant conducting cells. By focusing on the evolution of the key transcription factors that regulate vascular cell differentiation, the NAC transcription factor VASCULAR-RELATED NAC-DOMAIN for WCCs and the MYB-coiled-coil (CC)-type transcription factor ALTERED PHLOEM DEVELOPMENT for sieve elements, we describe how land plants evolved molecular systems to produce the specialized cells that function as WCCs and FCCs. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

FINITE-ELEMENT ANALYSIS OF MULTIPHASE IMMISCIBLE FLOW THROUGH SOILS

EPA Science Inventory

A finite-element model is developed for multiphase flow through soil involving three immiscible fluids: namely, air, water, and a nonaqueous phase liquid (NAPL). A variational method is employed for the finite-element formulation corresponding to the coupled differential equation...

CD4 T Cell Responses in Latent and Chronic Viral Infections

PubMed Central

Walton, Senta; Mandaric, Sanja; Oxenius, Annette

2013-01-01

The spectrum of tasks which is fulfilled by CD4 T cells in the setting of viral infections is large, ranging from support of CD8 T cells and humoral immunity to exertion of direct antiviral effector functions. While our knowledge about the differentiation pathways, plasticity, and memory of CD4 T cell responses upon acute infections or immunizations has significantly increased during the past years, much less is still known about CD4 T cell differentiation and their beneficial or pathological functions during persistent viral infections. In this review we summarize current knowledge about the differentiation, direct or indirect antiviral effector functions, and the regulation of virus-specific CD4 T cells in the setting of persistent latent or active chronic viral infections with a particular emphasis on herpes virus infections for the former and chronic lymphocytic choriomeningitis virus infection for the latter. PMID:23717308

Differential modulation of ROS signals and other mitochondrial parameters by the antioxidants MitoQ, resveratrol and curcumin in human adipocytes.

PubMed

Hirzel, Estelle; Lindinger, Peter W; Maseneni, Swarna; Giese, Maria; Rhein, Véronique Virginie; Eckert, Anne; Hoch, Matthias; Krähenbühl, Stephan; Eberle, Alex N

2013-10-01

Mitochondrial reactive oxygen species (ROS) have been demonstrated to play an important role as signaling and regulating molecules in human adipocytes. In order to evaluate the differential modulating roles of antioxidants, we treated human adipocytes differentiated from human bone marrow-derived mesenchymal stem cells with MitoQ, resveratrol and curcumin. The effects on ROS, viability, mitochondrial respiration and intracellular ATP levels were examined. MitoQ lowered both oxidizing and reducing ROS. Resveratrol decreased reducing and curcumin oxidizing radicals only. All three substances slightly decreased state III respiration immediately after addition. After 24 h of treatment, MitoQ inhibited both basal and uncoupled oxygen consumption, whereas curcumin and resveratrol had no effect. Intracellular ATP levels were not altered. This demonstrates that MitoQ, resveratrol and curcumin exert potent modulating effects on ROS signaling in human adipocyte with marginal effects on metabolic parameters.

Quantitative modeling and optimization of magnetic tweezers.

PubMed

Lipfert, Jan; Hao, Xiaomin; Dekker, Nynke H

2009-06-17

Magnetic tweezers are a powerful tool to manipulate single DNA or RNA molecules and to study nucleic acid-protein interactions in real time. Here, we have modeled the magnetic fields of permanent magnets in magnetic tweezers and computed the forces exerted on superparamagnetic beads from first principles. For simple, symmetric geometries the magnetic fields can be calculated semianalytically using the Biot-Savart law. For complicated geometries and in the presence of an iron yoke, we employ a finite-element three-dimensional PDE solver to numerically solve the magnetostatic problem. The theoretical predictions are in quantitative agreement with direct Hall-probe measurements of the magnetic field and with measurements of the force exerted on DNA-tethered beads. Using these predictive theories, we systematically explore the effects of magnet alignment, magnet spacing, magnet size, and of adding an iron yoke to the magnets on the forces that can be exerted on tethered particles. We find that the optimal configuration for maximal stretching forces is a vertically aligned pair of magnets, with a minimal gap between the magnets and minimal flow cell thickness. Following these principles, we present a configuration that allows one to apply > or = 40 pN stretching forces on approximately 1-microm tethered beads.

Quantitative Modeling and Optimization of Magnetic Tweezers

PubMed Central

Lipfert, Jan; Hao, Xiaomin; Dekker, Nynke H.

2009-01-01

Abstract Magnetic tweezers are a powerful tool to manipulate single DNA or RNA molecules and to study nucleic acid-protein interactions in real time. Here, we have modeled the magnetic fields of permanent magnets in magnetic tweezers and computed the forces exerted on superparamagnetic beads from first principles. For simple, symmetric geometries the magnetic fields can be calculated semianalytically using the Biot-Savart law. For complicated geometries and in the presence of an iron yoke, we employ a finite-element three-dimensional PDE solver to numerically solve the magnetostatic problem. The theoretical predictions are in quantitative agreement with direct Hall-probe measurements of the magnetic field and with measurements of the force exerted on DNA-tethered beads. Using these predictive theories, we systematically explore the effects of magnet alignment, magnet spacing, magnet size, and of adding an iron yoke to the magnets on the forces that can be exerted on tethered particles. We find that the optimal configuration for maximal stretching forces is a vertically aligned pair of magnets, with a minimal gap between the magnets and minimal flow cell thickness. Following these principles, we present a configuration that allows one to apply ≥40 pN stretching forces on ≈1-μm tethered beads. PMID:19527664

Differentiation-promoting activity of pomegranate (Punica granatum) fruit extracts in HL-60 human promyelocytic leukemia cells.

PubMed

Kawaii, Satoru; Lansky, Ephraim P

2004-01-01

Differentiation refers to the ability of cancer cells to revert to their normal counterparts, and its induction represents an important noncytotoxic therapy for leukemia, and also breast, prostate, and other solid malignancies. Flavonoids are a group of differentiation-inducing chemicals with a potentially lower toxicology profile than retinoids. Flavonoid-rich polyphenol fractions from the pomegranate (Punica granatum) fruit exert anti-proliferative, anti-invasive, anti-eicosanoid, and pro-apoptotic actions in breast and prostate cancer cells and anti-angiogenic activities in vitro and in vivo. Here we tested flavonoid-rich fractions from fresh (J) and fermented (W) pomegranate juice and from an aqueous extraction of pomegranate pericarps (P) as potential differentiation-promoting agents of human HL-60 promyelocytic leukemia cells. Four assays were used to assess differentiation: nitro blue tetrazolium reducing activity, nonspecific esterase activity, specific esterase activity, and phagocytic activity. In addition, the effect of these extracts on HL-60 proliferation was evaluated. Extracts W and P were strong promoters of differentiation in all settings, with extract J showing only a relatively mild differentiation-promoting effect. The extracts had proportional inhibitory effects on HL-60 cell proliferation. The results highlight an important, previously unknown, mechanism of the cancer preventive and suppressive potential of pomegranate fermented juice and pericarp extracts.

Regulation of collagenase-3 and osteocalcin gene expression by collagen and osteopontin in differentiating MC3T3-E1 cells

NASA Technical Reports Server (NTRS)

D'Alonzo, Richard C.; Kowalski, Aaron J.; Denhardt, David T.; Nickols, G. Allen; Partridge, Nicola C.

2002-01-01

Both collagenase-3 and osteocalcin mRNAs are expressed maximally during the later stages of osteoblast differentiation. Here, we demonstrate that collagenase-3 mRNA expression in differentiating MC3T3-E1 cells is dependent upon the presence of ascorbic acid, is inhibited in the presence of the collagen synthesis inhibitor, 3,4-dehydroproline, and is stimulated by growth on collagen in the absence of ascorbic acid. Transient transfection studies show that collagenase-3 promoter activity increases during cell differentiation and requires the presence of ascorbic acid. Additionally, we show that, in differentiating MC3T3-E1 cells, collagenase-3 gene expression increases in the presence of an anti-osteopontin monoclonal antibody that binds near the RGD motif of this protein, whereas osteocalcin expression is inhibited. Furthermore, an RGD peptidomimetic compound, designed to block interaction of ligands to the alpha(v) integrin subunit, increases osteocalcin expression and inhibits collagenase-3 expression, suggesting that the RGD peptidomimetic initiates certain alpha(v) integrin signaling in osteoblastic cells. Overall, these studies demonstrate that stimulation of collagenase-3 expression during osteoblast differentiation requires synthesis of a collagenous matrix and that osteopontin and alpha(v) integrins exert divergent regulation of collagenase-3 and osteocalcin expression during osteoblast differentiation.

How do leader-member exchange quality and differentiation affect performance in teams? An integrated multilevel dual process model.

PubMed

Li, Alex Ning; Liao, Hui

2014-09-01

Integrating leader-member exchange (LMX) research with role engagement theory (Kahn, 1990) and role system theory (Katz & Kahn, 1978), we propose a multilevel, dual process model to understand the mechanisms through which LMX quality at the individual level and LMX differentiation at the team level simultaneously affect individual and team performance. With regard to LMX differentiation, we introduce a new configural approach focusing on the pattern of LMX differentiation to complement the traditional approach focusing on the degree of LMX differentiation. Results based on multiphase, multisource data from 375 employees of 82 teams revealed that, at the individual level, LMX quality positively contributed to customer-rated employee performance through enhancing employee role engagement. At the team level, LMX differentiation exerted negative influence on teams' financial performance through disrupting team coordination. In particular, teams with the bimodal form of LMX configuration (i.e., teams that split into 2 LMX-based subgroups with comparable size) suffered most in team performance because they experienced greatest difficulty in coordinating members' activities. Furthermore, LMX differentiation strengthened the relationship between LMX quality and role engagement, and team coordination strengthened the relationship between role engagement and employee performance. Theoretical and practical implications of the findings are discussed. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Inhibitory effects of coumarins from the stem barks of Fraxinus rhynchophylla on adipocyte differentiation in 3T3-L1 cells.

PubMed

Shin, Eunjin; Choi, Kyeong-Mi; Yoo, Hwan-Soo; Lee, Chong-Kil; Hwang, Bang Yeon; Lee, Mi Kyeong

2010-01-01

In the course of screening anti-adipogenic activity of natural products employing the preadipocyte cell line, 3T3-L1 as an in vitro assay system, the EtOAc fraction of the stem barks of Fraxinus rhynchophylla DENCE (Oleaceae) showed significant inhibitory activity on adipocyte differentiation as assessed by measuring fat accumulation using Oil Red O staining. Activity-guided fractionation led to the isolation of six coumarins such as esculetin (1), scopoletin (2), fraxetin (3), fraxidin (4) esculin (5) and fraxin (6). Among the six coumarins isolated, esculetin (1) showed the most potent inhibitory activity on adipocyte differentiation, followed by fraxetin (3). Further studies with interval treatment demonstrated that esculetin (1) exerted inhibitory activity on adipocyte differentiation when treated within 2 d (days 0-2) after differentiation induction. We further investigated the effect of esculetin (1) on peroxisome proliferator activated receptor gamma (PPARgamma), one of the early adipogenic transcription factors. Esculetin (1) significantly blocked the induction of PPARgamma protein expression and inhibited adipocyte differentiation induced by troglitazone, a PPARgamma agonist. Taken together, these results suggest that esculetin (1), an active compound from F. rhynchophylla, inhibited early stage of adipogenic differentiation, in part, via inhibition of PPARgamma-dependent pathway.

The Influence of law on Strategy

DTIC Science & Technology

2016-05-26

Approved for public release; distribution is unlimited The Influence of Law on Strategy A Monograph by Kevin G. Rousseau School of Advanced...2016 4. TITLE AND SUBTITLE The Influence of Law on Strategy 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...NOTES 14. ABSTRACT Strategists must understand the legal dynamics that are exerting an increasingly powerful influence on the legitimate use of

Effects of environmental estrogenic chemicals on AP1 mediated transcription with estrogen receptors alpha and beta.

PubMed

Fujimoto, Nariaki; Honda, Hiroaki; Kitamura, Shigeyuki

2004-01-01

There has been much discussion concerning endocrine disrupting chemicals suspected of exerting adverse effects in both wildlife and humans. Since the majority of these compounds are estrogenic, a large number of in vitro tests for estrogenic characteristics have been developed for screening purpose. One reliable and widely used method is the reporter gene assay employing estrogen receptors (ERs) and a reporter gene with a cis-acting estrogen responsive element (ERE). Other elements such as AP1 also mediate estrogenic signals and the manner of response could be quite different from that of ERE. Since this has yet to be explored, the ER mediated AP1 activity in response to a series of environmental estrogens was investigated in comparison with ERE findings. All the compounds exhibited estrogenic properties with ERE-luc and their AP1 responses were quite similar. These was one exception, however, p,p'-DDT (1,1,1,-trichloro-2,2-bis(p-chlorophenyl)ethane) did not exert any AP1-luc activity, while it appeared to be estrogenic at 10(-7) to 10(-5)M with the ERE action. None of the compounds demonstrated ER beta:AP1 activity. These data suggest that significant differences can occur in responses through the two estrogen pathways depending on environmental chemicals.

Biomechanical analysis of acromioclavicular joint dislocation treated with clavicle hook plates in different lengths.

PubMed

Shih, Cheng-Min; Huang, Kui-Chou; Pan, Chien-Chou; Lee, Cheng-Hung; Su, Kuo-Chih

2015-11-01

Clavicle hook plates are frequently used in clinical orthopaedics to treat acromioclavicular joint dislocation. However, patients often exhibit acromion osteolysis and per-implant fracture after undergoing hook plate fixation. With the intent of avoiding future complications or fixation failure after clavicle hook plate fixation, we used finite element analysis (FEA) to investigate the biomechanics of clavicle hook plates of different materials and sizes when used in treating acromioclavicular joint dislocation. Using finite element analysis, this study constructed a model comprising four parts: clavicle, acromion, clavicle hook plate and screws, and used the model to simulate implanting different types of clavicle hook plates in patients with acromioclavicular joint dislocation. Then, the biomechanics of stainless steel and titanium alloy clavicle hook plates containing either six or eight screw holes were investigated. The results indicated that using a longer clavicle hook plate decreased the stress value in the clavicle, and mitigated the force that clavicle hook plates exert on the acromion. Using a clavicle hook plate material characterized by a smaller Young's modulus caused a slight increase in the stress on the clavicle. However, the external force the material imposed on the acromion was less than the force exerted on the clavicle. The findings of this study can serve as a reference to help orthopaedic surgeons select clavicle hook plates.

ALK and TGF-Beta Resistance in Breast Cancer

DTIC Science & Technology

2016-10-01

Oncogene, 2002. 21(7): p. 1038 -47. 10 . Khoury, J.D., et al., Differential expression and clinical significance of tyrosine-phosphorylated STAT3 in ALK...NUMBER Baylor College of Medicine Houston, TX 77030 9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10 . SPONSOR/MONITOR’S ACRONYM(S) 11. SPONSOR... 10 3 INTRODUCTION: TGF-β exerts its tumor suppressing function by inhibiting the growth of normal epithelial cells. Loss of the TGF-β

Truncated thioredoxin (Trx-80) promotes pro-inflammatory macrophages of the M1 phenotype and enhances atherosclerosis.

PubMed

Mahmood, Dler Faieeq Darweesh; Abderrazak, Amna; Couchie, Dominique; Lunov, Oleg; Diderot, Vimala; Syrovets, Tatiana; Slimane, Mohamed-Naceur; Gosselet, Fabien; Simmet, Thomas; Rouis, Mustapha; El Hadri, Khadija

2013-07-01

Vascular cells are particularly susceptible to oxidative stress that is believed to play a key role in the pathogenesis of cardiovascular disorders. Thioredoxin-1 (Trx-1) is an oxidative stress-limiting protein with anti-inflammatory and anti-apoptotic properties. In contrast, its truncated form (Trx-80) exerts pro-inflammatory effects. Here we analyzed whether Trx-80 might exert atherogenic effects by promoting macrophage differentiation into the M1 pro-inflammatory phenotype. Trx-80 at 1 µg/ml significantly attenuated the polarization of anti-inflammatory M2 macrophages induced by exposure to either IL-4 at 15 ng/ml or IL-4/IL-13 (10 ng/ml each) in vitro, as evidenced by the expression of the characteristic markers, CD206 and IL-10. By contrast, in LPS-challenged macrophages, Trx-80 significantly potentiated the differentiation into inflammatory M1 macrophages as indicated by the expression of the M1 cytokines, TNF-α and MCP-1. When Trx-80 was administered to hyperlipoproteinemic ApoE2.Ki mice at 30 µg/g body weight (b.w.) challenged either with LPS at 30 µg/30 g (b.w.) or IL-4 at 500 ng/30 g (b.w.), it significantly induced the M1 phenotype but inhibited differentiation of M2 macrophages in thymus and liver. When ApoE2.Ki mice were challenged once weekly with LPS for 5 weeks, they showed severe atherosclerotic lesions enriched with macrophages expressing predominantly M1 over M2 markers. Such effect was potentiated when mice received daily, in addition to LPS, the Trx-80. Moreover, the Trx-80 treatment led to a significantly increased aortic lesion area. The ability of Trx-80 to promote differentiation of macrophages into the classical proinflammatory phenotype may explain its atherogenic effects in cardiovascular diseases. Copyright © 2013 Wiley Periodicals, Inc.

Distemper virus encephalitis exerts detrimental effects on hippocampal neurogenesis.

PubMed

von Rüden, E-L; Avemary, J; Zellinger, C; Algermissen, D; Bock, P; Beineke, A; Baumgärtner, W; Stein, V M; Tipold, A; Potschka, H

2012-08-01

Despite knowledge about the impact of brain inflammation on hippocampal neurogenesis, data on the influence of virus encephalitis on dentate granule cell neurogenesis are so far limited. Canine distemper is considered an interesting model of virus encephalitis, which can be associated with a chronic progressing disease course and can cause symptomatic seizures. To determine the impact of canine distemper virus (CDV) infection on hippocampal neurogenesis, we compared post-mortem tissue from dogs with infection with and without seizures, from epileptic dogs with non-viral aetiology and from dogs without central nervous system diseases. The majority of animals with infection and with epilepsy of non-viral aetiology exhibited neuronal progenitor numbers below the age average in controls. Virus infection with and without seizures significantly decreased the mean number of neuronal progenitor cells by 43% and 76% as compared to age-matched controls. Ki-67 labelling demonstrated that hippocampal cell proliferation was neither affected by infection nor by epilepsy of non-viral aetiology. Analysis of CDV infection in cells expressing caspase-3, doublecortin or Ki-67 indicated that infection of neuronal progenitor cells is extremely rare and suggests that infection might damage non-differentiated progenitor cells, hamper neuronal differentiation and promote glial differentiation. A high inter-individual variance in the number of lectin-reactive microglial cells was evident in dogs with distemper infection. Statistical analyses did not reveal a correlation between the number of lectin-reactive microglia cells and neuronal progenitor cells. Our data demonstrate that virus encephalitis with and without seizures can exert detrimental effects on hippocampal neurogenesis, which might contribute to long-term consequences of the disease. The lack of a significant impact of distemper virus on Ki-67-labelled cells indicates that the infection affected neuronal differentiation and survival of newborn cells rather than hippocampal cell proliferation. © 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological Society.

Neuroendocrine Consequences of Androgen Excess in Female Rodents

PubMed Central

Foecking, Eileen M.; McDevitt, Melissa A.; Acosta-Martínez, Maricedes; Horton, Teresa H.; Levine, Jon E.

2008-01-01

Androgens exert significant organizational and activational effects on the nervous system and behavior. Despite the fact that female mammals generally produce low levels of androgens, relative to the male of the same species, increasing evidence suggests that androgens can exert profound effects on the normal physiology and behavior of females during fetal, neonatal, and adult stages of life. This review examines the effects of exposure to androgens at three stages of development – as an adult, during early postnatal life and as a fetus, on reproductive hormone secretions in female rats. We examine the effects of androgen exposure both as a model of neuroendocrine sexual differentiation and with respect to the role androgens play in the normal female. We then discuss the hypothesis that androgens may cause epigenetic modification of estrogen target genes in the brain. Finally we consider the clinical consequences of excess androgen exposure in women. PMID:18374922

Oral contraceptives and mood in women with and without premenstrual dysphoria: a theoretical model.

PubMed

Kurshan, N; Neill Epperson, C

2006-01-01

Despite numerous studies on the topic, there is no consensus to date on the effects of oral contraceptives on mood or the mechanism(s) by which they exert these effects. This review article presents a theoretical model to explain the way in which oral contraceptives may affect mood. Specifically, it is argued that progestins exert differential effects on endogenous levels of neurosteroids, thereby altering mood. After providing an overview of the effects of estrogen, progesterone, and progesterone's metabolites on cortical excitability and the role of neurosteroids in depression and premenstrual dysphoria, this article reviews the research that has been conducted on the relationship between oral contraceptives and neurosteroids. Finally, suggestions for future research are made with the dual aim of improving existing studies on the relationship between oral contraceptives and mood and further investigating the possibility that fluctuations in neurosteroid levels are responsible for the effects of oral contraceptives on mood.

Developing psychophysiological profiles for monitoring stress

NASA Astrophysics Data System (ADS)

Moldow, Roberta L.; Bergen, Michael T.; Belin, Kari; Bululu, Luba; Couso, Olivita; McLaughlin, Joselyn; Short, Kenneth R.; Servatius, Richard J.

2006-05-01

Training prepares first responders for disasters including terrorist attacks. To train effectively it should be as realistic as possible and elicit the stress response. We are developing a profile that will be a marker for intensity of stress as well as differentiate stress from exertion. We have monitored stress during several training scenarios for different groups including civilian SWAT teams and the military. In addition, we can monitor stress to exposure to nonlethal weapons. We have monitored stress during exposure to blunt impact using a paintball paradigm. We have measured salivary substances (such as cortisol and DHEA [markers for the hypothalamic-pituitary-adrenal axis]) and amylase [marker for the sympathetic branch of the autonomic nervous system], physiological parameters (such as activity and heart rate), and neuropsychological assessment tools (such as Borg's perceived exertion scale, Spielberger's STAI and Thayer's ADC). With these neuroendocrine, physiological and behavioral indices in hand, we are poised to examine stress induction in preparedness in trainees.

N-person differential games. Part 2: The penalty method

NASA Technical Reports Server (NTRS)

Chen, G.; Mills, W. H.; Zheng, Q.; Shaw, W. H.

1983-01-01

The equilibrium strategy for N-person differential games can be found by studying a min-max problem subject to differential systems constraints. The differential constraints are penalized and finite elements are used to compute numerical solutions. Convergence proof and error estimates are given. Numerical results are also included and compared with those obtained by the dual method.

School Leadership Actions to Support Differentiated Instruction

ERIC Educational Resources Information Center

Byars, Jennifer Pallon

2011-01-01

Schools are required to meet a range of students' learning needs and effective school leadership is needed for the implementation of pedagogical practices responsive to the challenges of increasing student diversity and academic accountability. Literature on differentiated instruction and its constituent elements suggests differentiation results…

Evidence for a high temperature differentiation in a molten earth: A preliminary appraisal

NASA Technical Reports Server (NTRS)

Murthy, V. Rama

1992-01-01

If the earth were molten during its later stages of accretion as indicated by the present understanding of planetary accretion process, the differentiation that led to the formation of the core and mantle must have occurred at high temperatures in the range of 3000-5000 K because of the effect of pressure on the temperature of melting in the interior of the earth. This calls into question the use of low-temperature laboratory measurements of partition coefficients of trace elements to make inferences about earth accretion and differentiation. The low temperature partition coefficients cannot be directly applied to high temperature fractionations because partition coefficients refer to an equilibrium specific to a temperature for a given reaction, and must change in some proportion to exp 1/RT. There are no laboratory data on partition coefficients at the high temperatures relevant to differentiation in the interior of the earth, and an attempt to estimate high temperature distribution coefficients of siderophile elements was made by considering the chemical potential of a given element at equilibrium and how this potential changes with temperature, under some specific assumptions.

Laser diagnostics of native cervix dabs with human papilloma virus in high carcinogenic risk

NASA Astrophysics Data System (ADS)

Peresunko, O. P.; Karpenko, Ju. G.; Burkovets, D. N.; Ivashko, P. V.; Nikorych, A. V.; Yermolenko, S. B.; Gruia, Ion; Gruia, M. J.

2015-11-01

The results of experimental studies of coordinate distributions of Mueller matrix elements of the following types of cervical scraping tissue are presented: rate- low-grade - highly differentiated dysplasia (CIN1-CIN3) - adenocarcinoma of high, medium and low levels of differentiation (G1-G3). The rationale for the choice of statistical points 1-4 orders polarized coherent radiation field, transformed as a result of interaction with the oncologic modified biological layers "epithelium-stroma" as a quantitative criterion of polarimetric optical differentiation state of human biological tissues are shown here. The analysis of the obtained Mueller matrix elements and statistical correlation methods, the systematized by types studied tissues is accomplished. The results of research images of Mueller matrix elements m34 for this type of pathology as low-grade dysplasia (CIN2), the results of its statistical and correlation analysis are presented.

Investigation of the differentiation of ex vivo nerve and fat tissues using laser-induced breakdown spectroscopy (LIBS): Prospects for tissue-specific laser surgery.

PubMed

Mehari, Fanuel; Rohde, Maximillian; Kanawade, Rajesh; Knipfer, Christian; Adler, Werner; Klämpfl, Florian; Stelzle, Florian; Schmidt, Michael

2016-10-01

In the present study, the elemental compositions of fat and nerve tissue during their plasma mediated laser ablation are studied in the context of tissue differentiation for laser surgery applications by using Laser-Induced Breakdown Spectroscopy (LIBS). Tissue samples of porcine fat and nerve were prepared as ex vivo experimental objects. Plasma mediated laser ablation is performed using an Nd : YAG laser in open air and under normal stray light conditions. The performed measurements suggest that the two tissue types show a high similarity in terms of qualitative elemental composition while at the same time revealing a distinct difference in the concentration of the constituent elements. Different analysis approaches are evaluated and discussed to optimize the tissue-differentiation performance of the LIBS approach. Plasma mediated laser tissue ablation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Minimal parameter solution of the orthogonal matrix differential equation

NASA Technical Reports Server (NTRS)

Bar-Itzhack, Itzhack Y.; Markley, F. Landis

1990-01-01

As demonstrated in this work, all orthogonal matrices solve a first order differential equation. The straightforward solution of this equation requires n sup 2 integrations to obtain the element of the nth order matrix. There are, however, only n(n-1)/2 independent parameters which determine an orthogonal matrix. The questions of choosing them, finding their differential equation and expressing the orthogonal matrix in terms of these parameters are considered. Several possibilities which are based on attitude determination in three dimensions are examined. It is shown that not all 3-D methods have useful extensions to higher dimensions. It is also shown why the rate of change of the matrix elements, which are the elements of the angular rate vector in 3-D, are the elements of a tensor of the second rank (dyadic) in spaces other than three dimensional. It is proven that the 3-D Gibbs vector (or Cayley Parameters) are extendable to other dimensions. An algorithm is developed emplying the resulting parameters, which are termed Extended Rodrigues Parameters, and numerical results are presented of the application of the algorithm to a fourth order matrix.

Minimal parameter solution of the orthogonal matrix differential equation

NASA Technical Reports Server (NTRS)

Baritzhack, Itzhack Y.; Markley, F. Landis

1988-01-01

As demonstrated in this work, all orthogonal matrices solve a first order differential equation. The straightforward solution of this equation requires n sup 2 integrations to obtain the element of the nth order matrix. There are, however, only n(n-1)/2 independent parameters which determine an orthogonal matrix. The questions of choosing them, finding their differential equation and expressing the orthogonal matrix in terms of these parameters are considered. Several possibilities which are based on attitude determination in three dimensions are examined. It is shown that not all 3-D methods have useful extensions to higher dimensions. It is also shown why the rate of change of the matrix elements, which are the elements of the angular rate vector in 3-D, are the elements of a tensor of the second rank (dyadic) in spaces other than three dimensional. It is proven that the 3-D Gibbs vector (or Cayley Parameters) are extendable to other dimensions. An algorithm is developed employing the resulting parameters, which are termed Extended Rodrigues Parameters, and numerical results are presented of the application of the algorithm to a fourth order matrix.

Reciprocal role of vitamin D receptor on β-catenin regulated keratinocyte proliferation and differentiation.

PubMed

Hu, Lizhi; Bikle, Daniel D; Oda, Yuko

2014-10-01

The active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), suppresses the proliferation while promoting the differentiation of keratinocytes through the vitamin D receptor (VDR). β-Catenin, on the other hand, promotes proliferation and blocks epidermal differentiation, although it stimulates hair follicle differentiation. In intestinal epithelia VDR binds β-catenin and blocks its proliferative effects. In this study we investigated the role of 1,25(OH)2D3/VDR on β-catenin regulated gene transcription during keratinocyte proliferation and differentiation. 1,25(OH)2D3 suppressed promoter reporter activity driven by synthetic and natural TCF/β-catenin response elements. Over-expression of VDR further suppressed these TCF/β-catenin promoter activities. 1,25(OH)2D3 also suppressed the mRNA expression of the β-catenin regulated gene Gli1 through VDR. These data were consistent with our previous observations that VDR silencing resulted in keratinocyte hyperproliferation with increased expression of Gli1 in vitro, whereas VDR null skin showed hyperproliferation in vivo. In contrast, 1,25(OH)2D3 induced expression of another β-catenin regulated gene, PADI1, important for both epidermal and hair follicle differentiation. Deletion of VDR resulted in defects in hair differentiation in vivo, with decreased expression of β-catenin regulated hair differentiation genes such as PADI1, hair keratin KRT31 and calcium binding protein S100a3. These genes possess vitamin D response elements (VDRE) adjacent to TCF/β-catenin response elements and are regulated by both VDR and β-catenin signaling. Therefore, we propose that VDR and β-catenin interact reciprocally to promote VDR stimulation of genes involved with differentiation that contain both VDR and β-catenin response elements while inhibiting β-catenin stimulation of genes involved with proliferation. Thus the major finding of this study is that while 1,25(OH)2D3/VDR inhibits the actions of β-catenin to promote keratinocyte proliferation, 1,25(OH)2D3/VDR promotes the ability of β-catenin to stimulate hair follicle differentiation. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. Copyright © 2013 Elsevier Ltd. All rights reserved.

Lateral Orbitofrontal Cortical Modulation on the Medial Prefrontal Cortex-Amygdala Pathway: Differential Regulation of Intra-Amygdala GABAA and GABAB Receptors.

PubMed

Chang, Chun-Hui

2017-07-01

The basolateral complex of the amygdala receives inputs from neocortical areas, including the medial prefrontal cortex and lateral orbitofrontal cortex. Earlier studies have shown that lateral orbitofrontal cortex activation exerts an inhibitory gating on medial prefrontal cortex-amygdala information flow. Here we examined the individual role of GABAA and GABAB receptors in this process. In vivo extracellular single-unit recordings were done in anesthetized rats. We searched amygdala neurons that fire in response to medial prefrontal cortex activation, tested lateral orbitofrontal cortex gating at different delays (lateral orbitofrontal cortex-medial prefrontal cortex delays: 25, 50, 100, 250, 500, and 1000 milliseconds), and examined differential contribution of GABAA and GABAB receptors with iontophoresis. Relative to baseline, lateral orbitofrontal cortex stimulation exerted an inhibitory modulatory gating on the medial prefrontal cortex-amygdala pathway and was effective up to a long delay of 500 ms (long-delay latencies at 100, 250, and 500 milliseconds). Moreover, blockade of intra-amygdala GABAA receptors with bicuculline abolished the lateral orbitofrontal cortex inhibitory gating at both short- (25 milliseconds) and long-delay (100 milliseconds) intervals, while blockade of GABAB receptors with saclofen reversed the inhibitory gating at long delay (100 milliseconds) only. Among the majority of the neurons examined (8 of 9), inactivation of either GABAA or GABAB receptors during baseline did not change evoked probability per se, suggesting that local feed-forward inhibitory mechanism is pathway specific. Our results suggest that the effect of lateral orbitofrontal cortex inhibitory modulatory gating was effective up to 500 milliseconds and that intra-amygdala GABAA and GABAB receptors differentially modulate the short- and long-delay lateral orbitofrontal cortex inhibitory gating on the medial prefrontal cortex-amygdala pathway. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Differentiating levels of surgical experience on a virtual reality temporal bone simulator.

PubMed

Zhao, Yi C; Kennedy, Gregor; Hall, Richard; O'Leary, Stephen

2010-11-01

Virtual reality simulation is increasingly being incorporated into surgical training and may have a role in temporal bone surgical education. Here we test whether metrics generated by a virtual reality surgical simulation can differentiate between three levels of experience, namely novices, otolaryngology residents, and experienced qualified surgeons. Cohort study. Royal Victorian Eye and Ear Hospital. Twenty-seven participants were recruited. There were 12 experts, six residents, and nine novices. After orientation, participants were asked to perform a modified radical mastoidectomy on the simulator. Comparisons of time taken, injury to structures, and forces exerted were made between the groups to determine which specific metrics would discriminate experience levels. Experts completed the simulated task in significantly shorter time than the other two groups (experts 22 minutes, residents 36 minutes, and novices 46 minutes; P = 0.001). Novices exerted significantly higher average forces when dissecting close to vital structures compared with experts (0.24 Newton [N] vs 0.13 N, P = 0.002). Novices were also more likely to injure structures such as dura compared to experts (23 injuries vs 3 injuries, P = 0.001). Compared with residents, the experts modulated their force between initial cortex dissection and dissection close to vital structures. Using the combination of these metrics, we were able to correctly classify the participants' level of experience 90 percent of the time. This preliminary study shows that measurements of performance obtained from within a virtual reality simulator can differentiate between levels of users' experience. These results suggest that simulator training may have a role in temporal bone training beyond foundational training. Copyright © 2010 American Academy of Otolaryngology–Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.

Differential effects of voluntary wheel running and toy rotation on the mRNA expression of neurotrophic factors and FKBP5 in a post-traumatic stress disorder rat model with the shuttle-box task.

PubMed

Tanichi, Masaaki; Toda, Hiroyuki; Shimizu, Kunio; Koga, Minori; Saito, Taku; Enomoto, Shingo; Boku, Shuken; Asai, Fumiho; Mitsui, Yumi; Nagamine, Masanori; Fujita, Masanori; Yoshino, Aihide

2018-06-18

Life-threatening experiences can result in the development of post-traumatic stress disorder. We have developed an animal model for post-traumatic stress disorder (PTSD) using a shuttle box in rats. In this paradigm, the rats were exposed to inescapable foot-shock stress (IS) in a shuttle box, and then an avoidance/escape task was performed in the same box 2 weeks after IS. A previous study using this paradigm revealed that environmental enrichment (EE) ameliorated avoidance/numbing-like behaviors, but not hyperarousal-like behaviors, and EE also elevated hippocampal brain-derived neurotrophic factor (BDNF) expression. However, the differential effects of EE components, i.e., running wheel (RW) or toy rotation, on PTSD-like behaviors has remained unclear. In this experiment, we demonstrated that RW, toy rotation, and EE (containing RW and toy rotation) ameliorated avoidance/numbing-like behaviors, induced learning of avoidance responses, and improved depressive-like behaviors in traumatized rats. The RW increased the hippocampal mRNA expression of neurotrophic factors, especially BDNF and glial-cell derived neurotrophic factor. Toy rotation influenced FK506 binding protein 5 mRNA expression, which is believed to be a regulator of the hypothalamic-pituitary-adrenal (HPA)-axis system, in the hippocampus and amygdala. This is the first report to elucidate the differential mechanistic effects of RW and toy rotation. The former appears to exert its effects via neurotrophic factors, while the latter exerts its effects via the HPA axis. Further studies will lead to a better understanding of the influence of environmental factors on PTSD. Copyright © 2018 Elsevier Inc. All rights reserved.

Resveratrol Exerts Dosage and Duration Dependent Effect on Human Mesenchymal Stem Cell Development

PubMed Central

Peltz, Lindsay; Gomez, Jessica; Marquez, Maribel; Alencastro, Frances; Atashpanjeh, Negar; Quang, Tara; Bach, Thuy; Zhao, Yuanxiang

2012-01-01

Studies in the past have illuminated the potential benefit of resveratrol as an anticancer (pro-apoptosis) and life-extending (pro-survival) compound. However, these two different effects were observed at different concentration ranges. Studies of resveratrol in a wide range of concentrations on the same cell type are lacking, which is necessary to comprehend its diverse and sometimes contradictory cellular effects. In this study, we examined the effects of resveratrol on cell self-renewal and differentiation of human mesenchymal stem cells (hMSCs), a type of adult stem cells that reside in a number of tissues, at concentrations ranging from 0.1 to 10 µM after both short- and long-term exposure. Our results reveal that at 0.1 µM, resveratrol promotes cell self-renewal by inhibiting cellular senescence, whereas at 5 µM or above, resveratrol inhibits cell self-renewal by increasing senescence rate, cell doubling time and S-phase cell cycle arrest. At 1 µM, its effect on cell self-renewal is minimal but after long-term exposure it exerts an inhibitory effect, accompanied with increased senescence rate. At all concentrations, resveratrol promotes osteogenic differentiation in a dosage dependent manner, which is offset by its inhibitory effect on cell self-renewal at high concentrations. On the contrary, resveratrol suppresses adipogenic differentiation during short-term exposure but promotes this process after long-term exposure. Our study implicates that resveratrol is the most beneficial to stem cell development at 0.1 µM and caution should be taken in applying resveratrol as an anticancer therapeutic agent or nutraceutical supplement due to its dosage dependent effect on hMSCs. PMID:22615926

The mitochondrial elongation factors MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics

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

Liu, Tong; Yu, Rong; Jin, Shao-Bo

2013-11-01

Mitochondria are dynamic organelles whose morphology is regulated by a complex balance of fission and fusion processes, and we still know relatively little about how mitochondrial dynamics is regulated. MIEF1 (also called MiD51) has recently been characterized as a key regulator of mitochondrial dynamics and in this report we explore the functions of its paralog MIEF2 (also called MiD49), to learn to what extent MIEF2 is functionally distinct from MIEF1. We show that MIEF1 and MIEF2 have many functions in common. Both are anchored in the mitochondrial outer membrane, recruit Drp1 from the cytoplasm to the mitochondrial surface and causemore » mitochondrial fusion, and MIEF2, like MIEF1, can interact with Drp1 and hFis1. MIEF1 and MIEF2, however, also differ in certain aspects. MIEF1 and MIEF2 are differentially expressed in human tissues during development. When overexpressed, MIEF2 exerts a stronger fusion-promoting effect than MIEF1, and in line with this, hFis1 and Mff can only partially revert the MIEF2-induced fusion phenotype, whereas MIEF1-induced fusion is reverted to a larger extent by hFis1 and Mff. MIEF2 forms high molecular weight oligomers, while MIEF1 is largely present as a dimer. Furthermore, MIEF1 and MIEF2 use distinct domains for oligomerization: in MIEF1, the region from amino acid residues 109–154 is required, whereas oligomerization of MIEF2 depends on amino acid residues 1 to 49, i.e. the N-terminal end. We also show that oligomerization of MIEF1 is not required for its mitochondrial localization and interaction with Drp1. In conclusion, our data suggest that the mitochondrial regulators MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics. - Highlights: • MIEF1 and MIEF2 recruit Drp1 to mitochondria and cause mitochondrial fusion. • MIEF2, like MIEF1, can interact with Drp1 and hFis1. • MIEF1 and MIEF2 are differentially expressed in human tissues during development. • MIEF2 exerts a stronger fusion-promoting effect than MIEF1. • MIEF2 can form oligomers, while MIEF1 is largely present as a dimer.« less

Chemical studies of elements with Z ⩾ 104 in gas phase

NASA Astrophysics Data System (ADS)

Türler, Andreas; Eichler, Robert; Yakushev, Alexander

2015-12-01

Chemical investigations of superheavy elements in the gas-phase, i.e. elements with Z ≥ 104, allow assessing the influence of relativistic effects on their chemical properties. Furthermore, for some superheavy elements and their compounds quite unique gas-phase chemical properties were predicted. The experimental verification of these properties yields supporting evidence for a firm assignment of the atomic number. Prominent examples are the high volatility observed for HsO4 or the very weak interaction of Cn with gold surfaces. The unique properties of HsO4 were exploited to discover the doubly-magic even-even nucleus 270Hs and the new isotope 271Hs. The combination of kinematic pre-separation and gas-phase chemistry allowed gaining access to a new class of relatively fragile compounds, the carbonyl complexes of elements Sg through Mt. A not yet resolved issue concerns the interaction of Fl with gold surfaces. While competing experiments agree on the fact that Fl is a volatile element, there are discrepancies concerning its adsorption on gold surfaces with respect to its daughter Cn. The elucidation of these and other questions amounts to the fascination that gas-phase chemical investigations exert on current research at the extreme limits of chemistry today.

Thrombomodulin exerts cytoprotective effect on low-dose UVB-irradiated HaCaT cells

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

Iwata, Masahiro; Laboratory of Vascular Medicine, Department of Cardiovascular and Respiratory Disorders Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520; Kawahara, Ko-ichi

Thrombomodulin (TM) is an endothelial cell surface anticoagulant glycoprotein that performs antimetastatic, angiogenic, adhesive, and anti-inflammatory functions in various tissues. It is also expressed in epidermal keratinocytes. We found that a physiological dose (10 mJ/cm{sup 2}) of mid-wavelength ultraviolet irradiation (UVB) significantly induced TM expression via the p38mitogen-activated protein kinase (MAPK)/cyclic AMP response element (CRE) signaling pathway in the epidermal keratinocyte cell line HaCaT; this shows that TM regulates the survival of HaCaT cells. SB203580, a p38MAPK inhibitor, significantly decreased TM expression and the viability of cells exposed to UVB. Furthermore, overexpression of TM markedly increased cell viability, and itmore » was abrogated by TM small interfering RNA (siRNA), suggesting that TM may play an important role in exerting cytoprotective effect on epidermal keratinocytes against low-dose UVB.« less

Good coercion: patients' moral evaluation of coercion in mental health care.

PubMed

Lorem, Geir F; Hem, Marit H; Molewijk, Bert

2015-06-01

The use of coercion in mental health care is not self-evident and requires moral justification. A joint understanding is difficult to achieve, because patients and health professionals often evaluate coercion differently. The present study aims to discuss patients' 'moral' evaluation of coercion. We believe that such a focus can form the basis for a better and more differentiated understanding of how we evaluate coercion. This is a qualitative study based on participant observation and interviews with patients. In order to focus specifically on the moral evaluation of coercion, we looked within patients' narratives to examine whether we could differentiate between how they experienced coercion and how they morally evaluated its use, and how they envision/describe good coercion. We found that patients differentiated implicitly between experiences and moral evaluation. The findings have been ordered into three types of reactions: agreeing and accepting, fighting or resisting, and resignation. Further reflection upon patients' positive and negative moral evaluations of coercion resulted in the formulation of different concrete elements at three levels: threshold elements, process elements, and empathic elements. These elements helped us to understand what these patients considered 'good coercion'. The implications are that good clinical practice cannot be separated from the formal, moral evaluation of coercion. A differentiated moral understanding of coercion can form the basis for better and more sensitive communication about coercion among all those involved. A more respectful dialogue on the moral evaluation of coercion might also raise awareness during both the decision-making process and the actual practising of coercion. © 2014 Australian College of Mental Health Nurses Inc.

Investigations into the Settlement and Attachment of Biofouling Marine Invertebrates

DTIC Science & Technology

2015-12-17

attachment of biofouling marine invertebrates 5a. CONTRACT NUMBER N00014-12-1 -0432 5b. GRANT NUMBER n/a 5c. PROGRAM ELEMENT NUMBER n/a 6...larval settlement in a variety of marine invertebrate species, including B. neritina. Light also inhibits B. neritina larval settlement, yet the...underlying mechanisms by which light and adrenergic compounds exert their effects on larvae are largely unknown. Octopamine is considered the invertebrate

The Strategic Plan: Is There Such a Thing for the Remotely Piloted Aircraft?

DTIC Science & Technology

2013-12-10

use this corporate definition, it provides useful insight. It accounts for the human element, or a thinking competitor, who exerts known and...in a while, everything about the world changes at once. This is one of those times. ―Chuck Klosterman quoted in Singer, Wired for War: The Robotics ...replacement to conventional forces on the battlefield. In the commercial sector, unmanned and robot technology is also increasing at unprecedented rates

Essential Oil of Pinus koraiensis Exerts Antiobesic and Hypolipidemic Activity via Inhibition of Peroxisome Proliferator-Activated Receptors Gamma Signaling.

PubMed

Ko, Hyun-Suk; Lee, Hyo-Jeong; Lee, Hyo-Jung; Sohn, Eun Jung; Yun, Miyong; Lee, Min-Ho; Kim, Sung-Hoon

2013-01-01

Our group previously reported that essential oil of Pinus koraiensis (EOPK) exerts antihyperlipidemic effects via upregulation of low-density lipoprotein receptor and inhibition of acyl-coenzyme A. In the present study, we investigated the antiobesity and hypolipidemic mechanism of EOPK using in vitro 3T3-L1 cells and in vivo HFD-fed rats. EOPK markedly suppressed fat accumulation and intracellular triglyceride associated with downregulation of adipogenic transcription factor expression, including PPAR γ and CEBP α in the differentiated 3T3-L1 adipocytes. Additionally, EOPK attenuated the expression levels of FABP and GPDH as target genes of PPAR γ during adipocyte differentiation. Furthermore, PPAR γ inhibitor GW9662 enhanced the decreased expression of FABP and PPAR γ and fat accumulation induced by EOPK. To confirm the in vitro activity of EOPK, animal study was performed by administering normal diet, HFD, and/or EOPK at the dose of 100 or 200 mg/kg for 6 weeks. Consistently, EOPK significantly suppressed body weight gain, serum triglyceride, total cholesterol, LDL cholesterol, and AI value and increased HDL cholesterol in a dose-dependent manner. Immunohistochemistry revealed that EOPK treatment abrogated the expression of PPAR γ in the liver tissue sections of EOPK-treated rats. Taken together, our findings suggest that EOPK has the antiobesic and hypolipidemic potential via inhibition of PPAR γ -related signaling.

Essential Oil of Pinus koraiensis Exerts Antiobesic and Hypolipidemic Activity via Inhibition of Peroxisome Proliferator-Activated Receptors Gamma Signaling

PubMed Central

Ko, Hyun-Suk; Lee, Hyo-Jeong; Lee, Hyo-Jung; Sohn, Eun Jung; Yun, Miyong; Lee, Min-Ho; Kim, Sung-Hoon

2013-01-01

Our group previously reported that essential oil of Pinus koraiensis (EOPK) exerts antihyperlipidemic effects via upregulation of low-density lipoprotein receptor and inhibition of acyl-coenzyme A. In the present study, we investigated the antiobesity and hypolipidemic mechanism of EOPK using in vitro 3T3-L1 cells and in vivo HFD-fed rats. EOPK markedly suppressed fat accumulation and intracellular triglyceride associated with downregulation of adipogenic transcription factor expression, including PPARγ and CEBPα in the differentiated 3T3-L1 adipocytes. Additionally, EOPK attenuated the expression levels of FABP and GPDH as target genes of PPARγ during adipocyte differentiation. Furthermore, PPARγ inhibitor GW9662 enhanced the decreased expression of FABP and PPARγ and fat accumulation induced by EOPK. To confirm the in vitro activity of EOPK, animal study was performed by administering normal diet, HFD, and/or EOPK at the dose of 100 or 200 mg/kg for 6 weeks. Consistently, EOPK significantly suppressed body weight gain, serum triglyceride, total cholesterol, LDL cholesterol, and AI value and increased HDL cholesterol in a dose-dependent manner. Immunohistochemistry revealed that EOPK treatment abrogated the expression of PPARγ in the liver tissue sections of EOPK-treated rats. Taken together, our findings suggest that EOPK has the antiobesic and hypolipidemic potential via inhibition of PPARγ-related signaling. PMID:23997801

Nezha, a novel active miniature inverted-repeat transposable element in cyanobacteria

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

Zhou Fengfeng; Tran Thao; Xu Ying

2008-01-25

Miniature inverted-repeat transposable elements (MITEs) were first identified in plants and exerted extensive proliferations throughout eukaryotic and archaeal genomes. But very few MITEs have been characterized in bacteria. We identified a novel MITE, called Nezha, in cyanobacteria Anabaena variabilis ATCC 29413 and Nostoc sp. PCC 7120. Nezha, like most previously known MITEs in other organisms, is small in size, non-coding, carrying TIR and DR signals, and of potential to form a stable RNA secondary structure, and it tends to insert into A+T-rich regions. Recent transpositions of Nezha were observed in A. variabilis ATCC 29413 and Nostoc sp. PCC 7120, respectively.more » Nezha might have proliferated recently with aid from the transposase encoded by ISNpu3-like elements. A possible horizontal transfer event of Nezha from cyanobacteria to Polaromonas JS666 is also observed.« less

mTOR complexes differentially orchestrates eosinophil development in allergy.

PubMed

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

2018-05-02

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

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

PubMed

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

2011-03-01

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

Differential action of glycoprotein hormones: significance in cancer progression.

PubMed

Govindaraj, Vijayakumar; Arya, Swathy V; Rao, A J

2014-02-01

Growth of multicellular organisms depends on maintenance of proper balance between proliferation and differentiation. Any disturbance in this balance in animal cells can lead to cancer. Experimental evidence is provided to conclude with special reference to the action of follicle-stimulating hormone (FSH) on Sertoli cells, and luteinizing hormone (LH) on Leydig cells that these hormones exert a differential action on their target cells, i.e., stimulate proliferation when the cells are in an undifferentiated state which is the situation with cancer cells and promote only functional parameters when the cell are fully differentiated. Hormones and growth factors play a key role in cell proliferation, differentiation, and apoptosis. There is a growing body of evidence that various tumors express some hormones at high levels as well as their cognate receptors indicating the possibility of a role in progression of cancer. Hormones such as LH, FSH, and thyroid-stimulating hormone have been reported to stimulate cell proliferation and act as tumor promoter in a variety of hormone-dependent cancers including gonads, lung, thyroid, uterus, breast, prostate, etc. This review summarizes evidence to conclude that these hormones are produced by some cancer tissues to promote their own growth. Also an attempt is made to explain the significance of the differential action of hormones in progression of cancer with special reference to prostate cancer.

Numerical computation of transonic flows by finite-element and finite-difference methods

NASA Technical Reports Server (NTRS)

Hafez, M. M.; Wellford, L. C.; Merkle, C. L.; Murman, E. M.

1978-01-01

Studies on applications of the finite element approach to transonic flow calculations are reported. Different discretization techniques of the differential equations and boundary conditions are compared. Finite element analogs of Murman's mixed type finite difference operators for small disturbance formulations were constructed and the time dependent approach (using finite differences in time and finite elements in space) was examined.

Differentiation characteristics and source analysis of heavy metals in typical brown soil under different vegetation

NASA Astrophysics Data System (ADS)

Dong, Zhicheng; Zhang, Lina; Li, Xueshuang; Lv, Shuangyan; He, Shijie; Liu, Ying; Ma, Xuanxuan

2017-08-01

Anomalous enrichment of soil elements (especially heavy metals) has aroused popular attention in China. In order to discuss distribution characteristics and analyze sources of elements in brown soil, field investigation and sample collection were carried out under different vegetation (cherry, apple, bamboos and pine) in Qixia, a typical apple production base in China. Element contents, pH, electrical conductivity (EC) and magnetic susceptibility (MS) were tested. Results showed that element concentrations were about roughly 2.48 times as China’s background values, while significantly lower than the class ii of National soil Environment Quality Standard (Ni excepted). Meanwhile, vertical distribution and accumulation characteristics of elements in typical brown soil were significantly different under different vegetation. In detail, elements (Zn excepted) of Pine soil accumulated in surface, while they (Cd, Arsenic excepted) increased with depth under other vegetation. Moreover, pH and EC changed like elements, while MS was exactly opposite. It was found that those differences above were mainly caused by human activities (such as improper use of fertilizer, pesticide and inadequate use of organic fertilizer, etc.). Additionally, differences in composition and decomposition rate of vegetation litter also resulted in vertical differentiations of soil elements under different vegetation.

Activation of dynamin I gene expression by Sp1 and Sp3 is required for neuronal differentiation of N1E-115 cells.

PubMed

Yoo, Jiyun; Jeong, Moon-Jin; Kwon, Byoung-Mog; Hur, Man-Wook; Park, Young-Mee; Han, Mi Young

2002-04-05

Dynamin I is a key molecule required for the recycling of synaptic vesicles in neurons, and it has been known that dynamin I gene expression is induced during neuronal differentiation. Our previous studies established that neuronal restriction of dynamin I gene expression is controlled by Sp1 and nuclear factor-kappaB-like element-1. Here, using a series of deletion constructs and site-directed mutation, we found that transcription of dynamin I gene during neuronal differentiation of N1E-115 cells is controlled primarily by the Sp1 element located between -13 to -4 bp of the dynamin I promoter. Gel shift analysis demonstrated that in addition to Sp1, Sp3 could interact with this Sp1 element. The requirement for Sp family transcription factors in dynamin I gene expression was confirmed by using mithramycin, an inhibitor of Sp1/Sp3 binding. Mithramycin repressed dynamin I gene expression and resulted in blocking of neuronal differentiation of N1E-115 cells. The localization of the dynamin I protein was also restricted in the peripheral region of the nucleus by the mithramycin treatment. Thus, all of our results suggest that induction of dynamin I gene expression during N1E-115 cell differentiation is modulated by Sp1/Sp3 interactions with the dynamin I promoter, and its expression is important for neuronal differentiation of the N1E-115 cells.

Crustal forensics in arc magmas

NASA Astrophysics Data System (ADS)

Davidson, Jon P.; Hora, John M.; Garrison, Jennifer M.; Dungan, Michael A.

2005-01-01

The geochemical characteristics of continental crust are present in nearly all arc magmas. These characteristics may reflect a specific source process, such as fluid fluxing, common to both arc magmas and the continental crust, and/or may reflect the incorporation of continental crust into arc magmas either at source via subducted sediment, or via contamination during differentiation. Resolving the relative mass contributions of juvenile, mantle-derived material, versus that derived from pre-existing crust of the upper plate, and providing these estimates on an element-by-element basis, is important because: (1) we want to constrain crustal growth rates; (2) we want to quantitatively track element cycling at convergent margins; and (3) we want to determine the origin of economically important elements and compounds. Traditional geochemical approaches for determining the contributions of various components to arc magmas are particularly successful when applied on a comparative basis. Studies of suites from multiple magmatic systems along arcs, for which differentiation effects can be individually constrained, can be used to extrapolate to potential source compositions. In the Lesser Antilles Arc, for example, differentiation trends from individual volcanoes are consistent with open-system evolution. However, such trends do not project back to a common primitive magma composition, suggesting that differentiation modifies magmas that were derived from distinct mantle sources. We propose that such approaches should now be complemented by petrographically constrained mineral-scale isotope and trace element analysis to unravel the contributing components to arc magmas. This innovative approach can: (1) better constrain true end-member compositions by returning wider ranges in geochemical compositions among constituent minerals than is found in whole rocks; (2) better determine magmatic evolution processes from core-rim isotopic or trace element profiles from the phases contained in magmas; and (3) constrain rates of differentiation by applying diffusion-controlled timescales to element profiles. An example from Nguaruhoe Volcano, New Zealand, underscores the importance of such a microsampling approach, showing that mineral isotopic compositions encompass wide ranges, that whole-rock isotopic compositions are consequently simply element-weighted averages of the heterogeneous crystal cargo, and that open-system evolution is proved by core-rim variations in Sr isotope ratios. Nguaruhoe is just one of many systems examined through microanalytical approaches. The overwhelming conclusion of these studies is that crystal cargoes are not truly phenocrystic, but are inherited from various sources. The implication of this realization is that the interpretation of whole-rock isotopic data, including the currently popular U-series, needs careful evaluation in the context of petrographic observations.

DIFFERENTIAL FAULT SENSING CIRCUIT

DOEpatents

Roberts, J.H.

1961-09-01

A differential fault sensing circuit is designed for detecting arcing in high-voltage vacuum tubes arranged in parallel. A circuit is provided which senses differences in voltages appearing between corresponding elements likely to fault. Sensitivity of the circuit is adjusted to some level above which arcing will cause detectable differences in voltage. For particular corresponding elements, a group of pulse transformers are connected in parallel with diodes connected across the secondaries thereof so that only voltage excursions are transmitted to a thyratron which is biased to the sensitivity level mentioned.

Backed Bending Actuator

NASA Technical Reports Server (NTRS)

Costen, Robert C.; Su, Ji

2004-01-01

Bending actuators of a proposed type would partly resemble ordinary bending actuators, but would include simple additional components that would render them capable of exerting large forces at small displacements. Like an ordinary bending actuator, an actuator according to the proposal would include a thin rectangular strip that would comprise two bonded layers (possibly made of electroactive polymers with surface electrodes) and would be clamped at one end in the manner of a cantilever beam. Unlike an ordinary bending actuator, the proposed device would include a rigid flat backplate that would support part of the bending strip against backward displacement; because of this feature, the proposed device is called a backed bending actuator. When an ordinary bending actuator is inactive, the strip typically lies flat, the tip displacement is zero, and the force exerted by the tip is zero. During activation, the tip exerts a transverse force and undergoes a bending displacement that results from the expansion or contraction of one or more of the bonded layers. The tip force of an ordinary bending actuator is inversely proportional to its length; hence, a long actuator tends to be weak. The figure depicts an ordinary bending actuator and the corresponding backed bending actuator. The bending, the tip displacement (d(sub t)), and the tip force (F) exerted by the ordinary bending actuator are well approximated by the conventional equations for the loading and deflection of a cantilever beam subject to a bending moment which, in this case, is applied by the differential expansion or contraction of the bonded layers. The bending, displacement, and tip force of the backed bending actuator are calculated similarly, except that it is necessary to account for the fact that the force F(sub b) that resists the displacement of the tip could be sufficient to push part of the strip against the backplate; in such a condition, the cantilever beam would be effectively shortened (length L*) and thereby stiffened and, hence, made capable of exerting a greater tip force for a given degree of differential expansion or contraction of the bonded layers. Taking all of these effects into account, the cantilever-beam equations show that F(sub b) would be approximately inversely proportional to d(sup 1/2) for d less than a calculable amount, denoted the transition displacement (dt). For d less than d(sub t), part of the strip would be pressed against the backplate. Therefore, the force F(sub b) would be very large for d at or near zero and would decrease as d increases toward d(sub t). At d greater than d(sub t), none of the strip would be pressed against the backplate and F(sub b) would equal the tip force F of the corresponding ordinary bending actuator. The advantage of the proposal is that a backed bending actuator could be made long to obtain large displacement when it encountered little resistance but it could also exert a large zero-displacement force, so that it could more easily start the movement of a large mass, throw a mechanical switch, or release a stuck mechanism.

Trace-element analyses of core samples from the 1967-1988 drillings of Kilauea Iki lava lake, Hawaii

USGS Publications Warehouse

Helz, Rosalind Tuthill

2012-01-01

This report presents previously unpublished analyses of trace elements in drill core samples from Kilauea Iki lava lake and from the 1959 eruption that fed the lava lake. The two types of data presented were obtained by instrumental neutron-activation analysis (INAA) and energy-dispersive X-ray fluorescence analysis (EDXRF). The analyses were performed in U.S. Geological Survey (USGS) laboratories from 1989 to 1994. This report contains 93 INAA analyses on 84 samples and 68 EDXRF analyses on 68 samples. The purpose of the study was to document trace-element variation during chemical differentiation, especially during the closed-system differentiation of Kilauea Iki lava lake.

A Four-Tier Differentiation Model: Engage All Students in the Learning Process

ERIC Educational Resources Information Center

Herrelko, Janet M.

2013-01-01

This study details the creation of a four-tiered format designed to help preservice teachers write differentiated lesson plans. A short history of lesson plan differentiation models is described and how the four-tier approach was developed through collaboration with classroom teachers and university faculty. The unifying element for the format…

Differentiated Instruction in a Data-Based Decision-Making Context

ERIC Educational Resources Information Center

Faber, Janke M.; Glas, Cees A. W.; Visscher, Adrie J.

2018-01-01

In this study, the relationship between differentiated instruction, as an element of data-based decision making, and student achievement was examined. Classroom observations (n = 144) were used to measure teachers' differentiated instruction practices and to predict the mathematical achievement of 2nd- and 5th-grade students (n = 953). The…

Complexity and Productivity Differentiation Models of Metallogenic Indicator Elements in Rocks and Supergene Media Around Daijiazhuang Pb-Zn Deposit in Dangchang County, Gansu Province

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

He, Jin-zhong, E-mail: viewsino@163.com; Yao, Shu-zhen; Zhang, Zhong-ping

2013-03-15

With the help of complexity indices, we quantitatively studied multifractals, frequency distributions, and linear and nonlinear characteristics of geochemical data for exploration of the Daijiazhuang Pb-Zn deposit. Furthermore, we derived productivity differentiation models of elements from thermodynamics and self-organized criticality of metallogenic systems. With respect to frequency distributions and multifractals, only Zn in rocks and most elements except Sb in secondary media, which had been derived mainly from weathering and alluviation, exhibit nonlinear distributions. The relations of productivity to concentrations of metallogenic elements and paragenic elements in rocks and those of elements strongly leached in secondary media can be seenmore » as linear addition of exponential functions with a characteristic weak chaos. The relations of associated elements such as Mo, Sb, and Hg in rocks and other elements in secondary media can be expressed as an exponential function, and the relations of one-phase self-organized geological or metallogenic processes can be represented by a power function, each representing secondary chaos or strong chaos. For secondary media, exploration data of most elements should be processed using nonlinear mathematical methods or should be transformed to linear distributions before processing using linear mathematical methods.« less

The use of multisensor data for robotic applications

NASA Technical Reports Server (NTRS)

Abidi, M. A.; Gonzalez, R. C.

1990-01-01

The feasibility of realistic autonomous space manipulation tasks using multisensory information is shown through two experiments involving a fluid interchange system and a module interchange system. In both cases, autonomous location of the mating element, autonomous location of the guiding light target, mating, and demating of the system were performed. Specifically, vision-driven techniques were implemented to determine the arbitrary two-dimensional position and orientation of the mating elements as well as the arbitrary three-dimensional position and orientation of the light targets. The robotic system was also equipped with a force/torque sensor that continuously monitored the six components of force and torque exerted on the end effector. Using vision, force, torque, proximity, and touch sensors, the two experiments were completed successfully and autonomously.

A HLA class I cis-regulatory element whose activity can be modulated by hormones.

PubMed

Sim, B C; Hui, K M

1994-12-01

To elucidate the basis of the down-regulation in major histocompatibility complex (MHC) class I gene expression and to identify possible DNA-binding regulatory elements that have the potential to interact with class I MHC genes, we have studied the transcriptional regulation of class I HLA genes in human breast carcinoma cells. A 9 base pair (bp) negative cis-regulatory element (NRE) has been identified using band-shift assays employing DNA sequences derived from the 5'-flanking region of HLA class I genes. This 9-bp element, GTCATGGCG, located within exon I of the HLA class I gene, can potently inhibit the expression of a heterologous thymidine kinase (TK) gene promoter and the HLA enhancer element. Furthermore, this regulatory element can exert its suppressive function in either the sense or anti-sense orientation. More interestingly, NRE can suppress dexamethasone-mediated gene activation in the context of the reported glucocorticoid-responsive element (GRE) in MCF-7 cells but has no influence on the estrogen-mediated transcriptional activation of MCF-7 cells in the context of the reported estrogen-responsive element (ERE). Furthermore, the presence of such a regulatory element within the HLA class I gene whose activity can be modulated by hormones correlates well with our observation that the level of HLA class I gene expression can be down-regulated by hormones in human breast carcinoma cells. Such interactions between negative regulatory elements and specific hormone trans-activators are novel and suggest a versatile form of transcriptional control.

Translations on Eastern Europe, Political, Sociological, and Military Affairs, Number 1320

DTIC Science & Technology

1976-11-17

behavior we should condemn. True enough, in the public pressure affecting our standard-of- living policies we can discover elements which are influenced...so that the supply of high- grade, healthful foods becomes still more polymorphic , abundant and appetiz- ing. Together with the All-Union Institute...death the Warsaw Pact nations will exert political and military pressure on Yugoslavia—and if need be will invade it—in order to force it to return to

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

Magnolol Enhances Hippocampal Neurogenesis and Exerts Antidepressant-Like Effects in Olfactory Bulbectomized Mice.

PubMed

Matsui, Nobuaki; Akae, Haruka; Hirashima, Nana; Kido, Yuki; Tanabe, Satoshi; Koseki, Mayumi; Fukuyama, Yoshiyasu; Akagi, Masaaki

2016-11-01

Magnolol is the main constituent of Magnolia bark and has been reported to exhibit antidepressant effects in rodent models. Hippocampal neurogenesis and neurotrophins such as brain-derived neurotrophic factor are integrally involved in the action of conventional antidepressants. Here, we investigated the effects of magnolol on depressive behaviours, impaired hippocampal neurogenesis and neurotrophin-related signal transduction in an olfactory bulbectomy (OBX) mouse model of depression. Mice were submitted to OBX to induce depressive behaviour, which was evaluated in the tail suspension test. Magnolol was administered orally by gavage needle. Neurogenesis was assessed by analysis of cells expressing NeuN, a neuronal marker, and 5-bromo-2'-deoxyuridine (BrdU) uptake. Phosphorylation levels of protein kinase B (Akt), extracellular signal-regulated kinase and cyclic AMP-responsive element-binding protein were evaluated by Western blot. Fourteen day treatment with magnolol (50 or 100 mg/kg/day) significantly improved OBX-induced depressive behaviour in tail suspension test. In agreement, magnolol significantly rescued impairments of hippocampal neurogenesis. Moreover, single treatments with magnolol (50 mg/kg) significantly increased phosphorylation of Akt, extracellular signal-regulated kinase and cyclic AMP-responsive element-binding protein after 3 h. The present data indicate that magnolol exerts antidepressant-like effects on behaviours by enhancing hippocampal neurogenesis and neurotrophin-related intracellular signalling in OBX mice. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

STATs shape the active enhancer landscape of T cell populations.

PubMed

Vahedi, Golnaz; Takahashi, Hayato; Nakayamada, Shingo; Sun, Hong-Wei; Sartorelli, Vittorio; Kanno, Yuka; O'Shea, John J

2012-11-21

Signaling pathways are intimately involved in cellular differentiation, allowing cells to respond to their environment by regulating gene expression. Although enhancers are recognized as key elements that regulate selective gene expression, the interplay between signaling pathways and actively used enhancer elements is not clear. Here, we use CD4(+) T cells as a model of differentiation, mapping the activity of cell-type-specific enhancer elements in T helper 1 (Th1) and Th2 cells. Our data establish that STAT proteins have a major impact on the activation of lineage-specific enhancers and the suppression of enhancers associated with alternative cell fates. Transcriptome analysis further supports a functional role for enhancers regulated by STATs. Importantly, expression of lineage-defining master regulators in STAT-deficient cells fails to fully recover the chromatin signature of STAT-dependent enhancers. Thus, these findings point to a critical role of STATs as environmental sensors in dynamically molding the specialized enhancer architecture of differentiating cells. Copyright © 2012 Elsevier Inc. All rights reserved.

STATs Shape the Active Enhancer Landscape of T Cell Populations

PubMed Central

Vahedi, Golnaz; Takahashi, Hayato; Nakayamada, Shingo; Sun, Hong-wei; Sartorelli, Vittorio; Kanno, Yuka; O’Shea, John J.

2012-01-01

SUMMARY Signaling pathways are intimately involved in cellular differentiation, allowing cells to respond to their environment by regulating gene expression. While enhancers are recognized as key elements that regulate selective gene expression, the interplay between signaling pathways and actively used enhancer elements is not clear. Here, we use CD4+ T cells as a model of differentiation, mapping the acquisition of cell-type-specific enhancer elements in T-helper 1 (Th1) and Th2 cells. Our data establish that STAT proteins have a major impact on the acquisition of lineage-specific enhancers and the suppression of enhancers associated with alternative cell fates. Transcriptome analysis further supports a functional role for enhancers regulated by STATs. Importantly, expression of lineage-defining master regulators in STAT-deficient cells fails to fully recover the chromatin signature of STAT-dependent enhancers. Thus, these findings point to a critical role of STATs as environmental sensors in dynamically molding the specialized enhancer architecture of differentiating cells. PMID:23178119

Photospheric Magnetic Flux Transport - Supergranules Rule

NASA Technical Reports Server (NTRS)

Hathaway, David H.; Rightmire-Upton, Lisa

2012-01-01

Observations of the transport of magnetic flux in the Sun's photosphere show that active region magnetic flux is carried far from its origin by a combination of flows. These flows have previously been identified and modeled as separate axisymmetric processes: differential rotation, meridional flow, and supergranule diffusion. Experiments with a surface convective flow model reveal that the true nature of this transport is advection by the non-axisymmetric cellular flows themselves - supergranules. Magnetic elements are transported to the boundaries of the cells and then follow the evolving boundaries. The convective flows in supergranules have peak velocities near 500 m/s. These flows completely overpower the superimposed 20 m/s meridional flow and 100 m/s differential rotation. The magnetic elements remain pinned at the supergranule boundaries. Experiments with and without the superimposed axisymmetric photospheric flows show that the axisymmetric transport of magnetic flux is controlled by the advection of the cellular pattern by underlying flows representative of deeper layers. The magnetic elements follow the differential rotation and meridional flow associated with the convection cells themselves -- supergranules rule!

AP-1 proteins in the adult brain: facts and fiction about effectors of neuroprotection and neurodegeneration.

PubMed

Herdegen, T; Waetzig, V

2001-04-30

Jun and Fos proteins are induced and activated following most physiological and pathophysiological stimuli in the brain. Only few data allow conclusions about distinct functions of AP-1 proteins in neurodegeneration and neuroregeneration, and these functions mainly refer to c-Jun and its activation by JNKs. Apoptotic functions of activated c-Jun affect hippocampal, nigral and primary cultured neurons following excitotoxic stimulation and destruction of the neuron-target-axis including withdrawal of trophic molecules. The inhibition of JNKs might exert neuroprotection by subsequent omission of c-Jun activation. Besides endogenous neuronal functions, the c-Jun/AP-1 proteins can damage the nervous system by upregulation of harmful programs in non-neuronal cells (e.g. microglia) with release of neurodegenerative molecules. In contrast, the differentiation with neurite extension and maturation of neural cells in vitro indicate physiological and potentially neuroprotective functions of c-Jun and JNKs including sensoring for alterations in the cytoskeleton. This review summarizes the multiple molecular interfunctions which are involved in the shift from the physiological role to degenerative effects of the Jun/JNK-axis such as cell type-specific expression and intracellular localization of scaffold proteins and upstream activators, antagonistic phosphatases, interaction with other kinase systems, or the activation of transcription factors competing for binding to JNK proteins and AP-1 DNA elements.

Cistrome of the aldosterone-activated mineralocorticoid receptor in human renal cells.

PubMed

Le Billan, Florian; Khan, Junaid A; Lamribet, Khadija; Viengchareun, Say; Bouligand, Jérôme; Fagart, Jérôme; Lombès, Marc

2015-09-01

Aldosterone exerts its effects mainly by activating the mineralocorticoid receptor (MR), a transcription factor that regulates gene expression through complex and dynamic interactions with coregulators and transcriptional machinery, leading to fine-tuned control of vectorial ionic transport in the distal nephron. To identify genome-wide aldosterone-regulated MR targets in human renal cells, we set up a chromatin immunoprecipitation (ChIP) assay by using a specific anti-MR antibody in a differentiated human renal cell line expressing green fluorescent protein (GFP)-MR. This approach, coupled with high-throughput sequencing, allowed identification of 974 genomic MR targets. Computational analysis identified an MR response element (MRE) including single or multiple half-sites and palindromic motifs in which the AGtACAgxatGTtCt sequence was the most prevalent motif. Most genomic MR-binding sites (MBSs) are located >10 kb from the transcriptional start sites of target genes (84%). Specific aldosterone-induced recruitment of MR on the first most relevant genomic sequences was further validated by ChIP-quantitative (q)PCR and correlated with concomitant and positive aldosterone-activated transcriptional regulation of the corresponding gene, as assayed by RT-qPCR. It was notable that most MBSs lacked MREs but harbored DNA recognition motifs for other transcription factors (FOX, EGR1, AP1, PAX5) suggesting functional interaction. This work provides new insights into aldosterone MR-mediated renal signaling and opens relevant perspectives for mineralocorticoid-related pathophysiology. © FASEB.

Auditory hair cell centrioles undergo confined Brownian motion throughout the developmental migration of the kinocilium.

PubMed

Lepelletier, Léa; de Monvel, Jacques Boutet; Buisson, Johanna; Desdouets, Chantal; Petit, Christine

2013-07-02

Planar polarization of the forming hair bundle, the mechanosensory antenna of auditory hair cells, depends on the poorly characterized center-to-edge displacement of a primary cilium, the kinocilium, at their apical surface. Taking advantage of the gradient of hair cell differentiation along the cochlea, we reconstituted a map of the kinocilia displacements in the mouse embryonic cochlea. We then developed a cochlear organotypic culture and video-microscopy approach to monitor the movements of the kinocilium basal body (mother centriole) and its daughter centriole, which we analyzed using particle tracking and modeling. We found that both hair cell centrioles undergo confined Brownian movements around their equilibrium positions, under the apparent constraint of a radial restoring force of ∼0.1 pN. This magnitude depended little on centriole position, suggesting nonlinear interactions with constraining, presumably cytoskeletal elements. The only dynamic change observed during the period of kinocilium migration was a doubling of the centrioles' confinement area taking place early in the process. It emerges from these static and dynamic observations that kinocilia migrate gradually in parallel with the organization of hair cells into rows during cochlear neuroepithelium extension. Analysis of the confined motion of hair cell centrioles under normal and pathological conditions should help determine which structures contribute to the restoring force exerting on them. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Auditory Hair Cell Centrioles Undergo Confined Brownian Motion Throughout the Developmental Migration of the Kinocilium

PubMed Central

Lepelletier, Léa; de Monvel, Jacques Boutet; Buisson, Johanna; Desdouets, Chantal; Petit, Christine

2013-01-01

Planar polarization of the forming hair bundle, the mechanosensory antenna of auditory hair cells, depends on the poorly characterized center-to-edge displacement of a primary cilium, the kinocilium, at their apical surface. Taking advantage of the gradient of hair cell differentiation along the cochlea, we reconstituted a map of the kinocilia displacements in the mouse embryonic cochlea. We then developed a cochlear organotypic culture and video-microscopy approach to monitor the movements of the kinocilium basal body (mother centriole) and its daughter centriole, which we analyzed using particle tracking and modeling. We found that both hair cell centrioles undergo confined Brownian movements around their equilibrium positions, under the apparent constraint of a radial restoring force of ∼0.1 pN. This magnitude depended little on centriole position, suggesting nonlinear interactions with constraining, presumably cytoskeletal elements. The only dynamic change observed during the period of kinocilium migration was a doubling of the centrioles’ confinement area taking place early in the process. It emerges from these static and dynamic observations that kinocilia migrate gradually in parallel with the organization of hair cells into rows during cochlear neuroepithelium extension. Analysis of the confined motion of hair cell centrioles under normal and pathological conditions should help determine which structures contribute to the restoring force exerting on them. PMID:23823223

Authentication of Kalix (N.E. Sweden) vendace caviar using inductively coupled plasma-based analytical techniques: evaluation of different approaches.

PubMed

Rodushkin, I; Bergman, T; Douglas, G; Engström, E; Sörlin, D; Baxter, D C

2007-02-05

Different analytical approaches for origin differentiation between vendace and whitefish caviars from brackish- and freshwaters were tested using inductively coupled plasma double focusing sector field mass spectrometry (ICP-SFMS) and multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS). These approaches involve identifying differences in elemental concentrations or sample-specific isotopic composition (Sr and Os) variations. Concentrations of 72 elements were determined by ICP-SFMS following microwave-assisted digestion in vendace and whitefish caviar samples from Sweden (from both brackish and freshwater), Finland and USA, as well as in unprocessed vendace roe and salt used in caviar production. This data set allows identification of elements whose contents in caviar can be affected by salt addition as well as by contamination during production and packaging. Long-term method reproducibility was assessed for all analytes based on replicate caviar preparations/analyses and variations in element concentrations in caviar from different harvests were evaluated. The greatest utility for differentiation was demonstrated for elements with varying concentrations between brackish and freshwaters (e.g. As, Br, Sr). Elemental ratios, specifically Sr/Ca, Sr/Mg and Sr/Ba, are especially useful for authentication of vendace caviar processed from brackish water roe, due to the significant differences between caviar from different sources, limited between-harvest variations and relatively high concentrations in samples, allowing precise determination by modern analytical instrumentation. Variations in the 87Sr/86Sr ratio for vendace caviar from different harvests (on the order of 0.05-0.1%) is at least 10-fold less than differences between caviar processed from brackish and freshwater roe. Hence, Sr isotope ratio measurements (either by ICP-SFMS or by MC-ICP-MS) have great potential for origin differentiation. On the contrary, it was impossible to differentiate between Swedish caviar processed from brackish water roe and Finnish freshwater caviar based solely on 187Os/188Os ratios.

Partition Coefficients at High Pressure and Temperature

NASA Astrophysics Data System (ADS)

Righter, K.; Drake, M. J.

2003-12-01

Differentiation of terrestrial planets includes separation of a metallic core and possible later fractionation of mineral phases within either a solid or molten mantle (Figure 1). Lithophile and siderophile elements can be used to understand these two different physical processes, and ascertain whether they operated in the early Earth. The distribution of elements in planets can be understood by measuring the partition coefficient, D (ratio of concentrations of an element in different phases (minerals, metals, or melts)). (14K)Figure 1. Schematic cross-section through the Earth, showing: (a) an early magma ocean stage and (b) a later cool and differentiated stage. The siderophile elements (iron-loving) encompass over 30 elements and are defined as those elements for which D(metal/silicate)>1, and are useful for deciphering the details of core formation. This group of elements is commonly broken up into several subclasses, including the slightly siderophile elements (1104). Because these three groups encompass a wide range of partition coefficient values, they can be very useful in trying to determine the conditions under which metal may have equilibrated with the mantle (or a magma ocean). Because metal and silicate may equilibrate by several different mechanisms, such as at the base of a deep magma ocean, or as metal droplets descend through a molten mantle, partition coefficients can potentially shed light on which mechanism may be most important, thus linking the physics and chemistry of core formation. In this chapter, we summarize metal/silicate partitioning of siderophile elements and show how they may be used to understand planetary core formation.Once a planet is differentiated into core and mantle, a mantle will cool during convection, and can start in either a molten or solid state, depending upon the initial thermal conditions. If hot enough, minerals will crystallize from a molten mantle, and become entrained in the convecting melt, or eventually settle out at the bottom. The entrainment and settling process has been studied in detail (e.g., Tonks and Melosh, 1990), and is a potential mechanism for differentiation between the deep and shallow parts of Earth's mantle. The lithophile elements, those elements that have D(metal/silicate) <1, fall into many different subclasses and all hold information about the deep mineral structure of the mantle. Rare-earth elements (REEs) have proven to be useful: europium anomalies have helped elucidate the role of plagioclase in lunar crust formation (e.g., Schnetzler and Philpotts, 1971; Weill et al., 1974), and LREE/HREE depletion and enrichment are indicators of partial melting in the presence of garnet in the mantle. High-field-strength elements (HFSEs) - niobium, zirconium, tantalum, and hafnium - are all refractory and hence more resilient to fractionation processes such as volatility or condensation. They also have an affinity for ilmenite and rutile, and can explain differences between lunar and martian samples as well as features of Earth's continental crust ( Taylor and McLennan, 1985). Alkaline-earth and alkaline elements include rubidium, strontium, barium, potassium, caesium, and calcium, some of which are involved in radioactive decay couples, e.g., Rb-Sr and K-Ar. The latter is important in understanding the contribution of radioactive decay to planetary heat production, and potential deep sources of radiogenic argon (see Chapter 2.06). Rubidium and potassium are further useful as tracers of hydrous phases such as mica and amphibole. Possible fractionation of any of these elements from chondritic abundances (see Chapter 2.01) can be assessed with the knowledge of partition coefficients. In this chapter we summarize our understanding of mineral/melt fractionation of minor and trace elements at high pressures and temperatures and discuss the implications for mantle differentiation.

Geochemistry of Groundwater

NASA Astrophysics Data System (ADS)

Chapelle, F. H.

2003-12-01

Differentiation of terrestrial planets includes separation of a metallic core and possible later fractionation of mineral phases within either a solid or molten mantle (Figure 1). Lithophile and siderophile elements can be used to understand these two different physical processes, and ascertain whether they operated in the early Earth. The distribution of elements in planets can be understood by measuring the partition coefficient, D (ratio of concentrations of an element in different phases (minerals, metals, or melts)). (14K)Figure 1. Schematic cross-section through the Earth, showing: (a) an early magma ocean stage and (b) a later cool and differentiated stage. The siderophile elements (iron-loving) encompass over 30 elements and are defined as those elements for which D(metal/silicate)>1, and are useful for deciphering the details of core formation. This group of elements is commonly broken up into several subclasses, including the slightly siderophile elements (1104). Because these three groups encompass a wide range of partition coefficient values, they can be very useful in trying to determine the conditions under which metal may have equilibrated with the mantle (or a magma ocean). Because metal and silicate may equilibrate by several different mechanisms, such as at the base of a deep magma ocean, or as metal droplets descend through a molten mantle, partition coefficients can potentially shed light on which mechanism may be most important, thus linking the physics and chemistry of core formation. In this chapter, we summarize metal/silicate partitioning of siderophile elements and show how they may be used to understand planetary core formation.Once a planet is differentiated into core and mantle, a mantle will cool during convection, and can start in either a molten or solid state, depending upon the initial thermal conditions. If hot enough, minerals will crystallize from a molten mantle, and become entrained in the convecting melt, or eventually settle out at the bottom. The entrainment and settling process has been studied in detail (e.g., Tonks and Melosh, 1990), and is a potential mechanism for differentiation between the deep and shallow parts of Earth's mantle. The lithophile elements, those elements that have D(metal/silicate) <1, fall into many different subclasses and all hold information about the deep mineral structure of the mantle. Rare-earth elements (REEs) have proven to be useful: europium anomalies have helped elucidate the role of plagioclase in lunar crust formation (e.g., Schnetzler and Philpotts, 1971; Weill et al., 1974), and LREE/HREE depletion and enrichment are indicators of partial melting in the presence of garnet in the mantle. High-field-strength elements (HFSEs) - niobium, zirconium, tantalum, and hafnium - are all refractory and hence more resilient to fractionation processes such as volatility or condensation. They also have an affinity for ilmenite and rutile, and can explain differences between lunar and martian samples as well as features of Earth's continental crust ( Taylor and McLennan, 1985). Alkaline-earth and alkaline elements include rubidium, strontium, barium, potassium, caesium, and calcium, some of which are involved in radioactive decay couples, e.g., Rb-Sr and K-Ar. The latter is important in understanding the contribution of radioactive decay to planetary heat production, and potential deep sources of radiogenic argon (see Chapter 2.06). Rubidium and potassium are further useful as tracers of hydrous phases such as mica and amphibole. Possible fractionation of any of these elements from chondritic abundances (see Chapter 2.01) can be assessed with the knowledge of partition coefficients. In this chapter we summarize our understanding of mineral/melt fractionation of minor and trace elements at high pressures and temperatures and discuss the implications for mantle differentiation.

A multidisciplinary investigation of groundwater fluctuations and their control on river chemistry - Insights from river dissolved concentrations and Li isotopes during flood events

NASA Astrophysics Data System (ADS)

Kuessner, M.; Bouchez, J.; Dangeard, M.; Bodet, L.; Thiesson, J.; Didon-Lescot, J. F.; Frick, D. A.; Grard, N.; Guérin, R.; Domergue, J. M.; Gaillardet, J.

2017-12-01

Water flow exerts a strong control on weathering reactions in the Critical Zone (CZ). The relationships between hydrology and river chemistry have been widely studied for the past decades [1]. Solute export responds strongly to storm events [2] and investigating the concentration and isotope composition of trace elements in river catchments can advance our understanding of the processes governing water-rock interactions and provide information on the water flow paths during these "hot moments". Especially, lithium (Li) and its isotopes are sensitive to the balance between mineral dissolution and precipitation in the subsurface and therefore, a powerful tool to characterize the response of chemical weathering to hydrology [3]. Hence, high-frequency stream chemistry yields valuable insight into the hydrological processes within the catchment during "hot moments". This study focuses on a CZ Observatory (OHMCV, part of French Research Infrastructure OZCAR). The granitic catchment Sapine (0.54 km2, southern France) is afflicted by big rain events and therefore, it is an appropriate location to study stormflows. Here we combine results from high-frequency stream water sampling during rain events with time-lapse seismic imaging to monitor the changes in aquifer properties [4]. The relationships between concentrations and discharge indicate differential responses of dissolved elements to the hydrological forcing. Especially, systematic changes are observed for Li and its isotopes as a function of water discharge, suggesting maximum secondary mineral formation at intermediate discharge. We suggest that Li dynamics are chiefly influenced by the depth at which water is flowing with, e.g. dissolution of primary minerals in deeper groundwater flows, and water-secondary mineral interaction at shallower depths. The combination of elemental concentrations and Li isotopes in river dissolved load tracing chemical weathering, with hydrogeophysical methods mapping water flows and pools, provides us with a time-resolved image of the CZ, improving our knowledge of the impact of hydrological changes on the chemical mass budgets in catchments. [1] Maher et al. (2011), Earth Planet. Sci. Lett. [2] Kirchner et al. (2010), Hydrol. Processes. [3] Liu et al. (2015), Earth Planet. Sci. Lett. [4] see poster by M. Dangeard et al.

FOXM1: A novel drug target in gastroenteropancreatic neuroendocrine tumors

PubMed Central

Briest, Franziska; Berg, Erika; Grass, Irina; Freitag, Helma; Kaemmerer, Daniel; Lewens, Florentine; Christen, Friederike; Arsenic, Ruza; Altendorf-Hofmann, Annelore; Kunze, Almut; Sänger, Jörg; Knösel, Thomas; Siegmund, Britta; Hummel, Michael; Grabowski, Patricia

2015-01-01

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are heterogeneous tumors that need to be molecularly defined to obtain novel therapeutic options. Forkheadbox protein M1 (FOXM1) is a crucial transcription factor in neoplastic cells and has been associated with differentiation and proliferation. We found that FOXM1 is strongly associated with tumor differentiation and occurrence of metastases in gastrointestinal NENs. In vitro inhibition by the FOXM1 inhibitor siomycin A led to down-regulation of mitotic proteins and resulted in a strong inhibitory effect. Siomycin A decreased mitosis rate, induced apoptosis in GEP-NEN cell lines and exerts synergistic effects with chemotherapy. FOXM1 is associated with clinical outcome and FOXM1 inhibition impairs survival in vitro. We therefore propose FOXM1 as novel therapeutic target in GEP-NENs. PMID:25797272

Resonance Properties of Class I and Class II Neurons Differentially Modulated by Channel Noise

NASA Astrophysics Data System (ADS)

Wang, Lei

2018-01-01

Resonance properties of two different neuron types (Class I and Class II) induced by channel noise are investigated in this study. It is found that for Class I neuron, spiking activity is enhanced when certain noise intensity is presented, especially under weak current stimuli -- a typical phenomenon of stochastic resonance (SR); while for Class II neuron, in addition to perform the SR, certain noise intensity would inhibit neuronal activity under some current stimuli -- a typical phenomenon of inverse stochastic resonance (ISR). Moreover, we show that only sodium channel noise or potassium channel noise variation can achieve the similar phenomena. Consequently, the model results suggest that channel noise may exert differential roles in modulating the resonance properties of Class I and Class II neurons.

Geochemistry of oceanic igneous rocks - Ridges, islands, and arcs - With emphasis on manganese, scandium, and vanadium

USGS Publications Warehouse

Doe, B.R.

1997-01-01

A database on a number of elements in oceanic volcanic rocks is presented, including the principal major-element oxides - SiO2, TiO2, Al2O3, Fe2O3(T), MnO, MgO, CaO, Na2O, K2O, and P2O5 (where T refers to total iron) - and the trace elements - Ba, Ce, Cr, Cu, Ni, Sc, Sr, V, Pb (mainly by isotope dilution), Yb, Zn, and Zr. Interpretations are given for transition metals, with emphasis on Mn, Sc, and V, in order to determine the concentration of the elements in primitive melts and assess their trends in magmatic differentiation. Transition metals are not enriched in plagioclase, so all are incompatible with pure plagioclase removal - that is, they become enriched in the melt. Both Cr and Ni are known to be highly compatible with olivine separation - i.e., they are depleted in the melt early in differentiation. Also, Sc is compatible with clinopyroxene (Cpx) removal from the melt and is depleted by separation of Cpx. Copper does not fit well in any of the principal silicates, but Cu, like Ni, is greatly enriched in sulfides that may remain in the source or separate from the magma. Decreasing Ni abundances and increasing Cu contents during differentiation are a sign of olivine separation. In the analysis presented herein, V - in the absence of Cpx separation - is found to behave remarkably like the moderately incompatible element Zn, and these two elements add to the list of element pairs of similar incompatibility whose ratios are insensitive to differentiation and to submarine weathering as well. Both are enhanced in titanomagnetite, so both would he compatible during titanomagnetite separation. When Cpx separates, however, V becomes compatible like Sc, but Zn remains incompatible. Thus, decreasing V (and Sc) contents and increasing Zn contents during differentiation are a sign of Cpx separation. Manganese often behaves much like Zn and therefore is moderately incompatible, but Mn is less compatible than Zn and V in titanomagnetite. Thus, decreasing Zn and V with increasing Mn is an indication of titanomagnetite removal. Dual compatible and incompatible trends with differentiation are found chiefly for Cu, Sc, and Sr. Distinguishing mid-ocean ridge basalts (MORB), oceanic-island volcanic rocks (OIV), and island-arc volcanic rocks (IAV) may be accomplished by plots of Ce/Yb versus Ba/Ce, where OIV plot to higher values of Ce/Yb than do MORB, and IAV data plot to higher values of Ba/Ce than do those of MORB. These ratios do not seem to be significantly affected by submarine weathering.

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.

5,6-Dehydrokawain from Alpinia zerumbet promotes osteoblastic MC3T3-E1 cell differentiation.

PubMed

Kumagai, Momochika; Mishima, Takashi; Watanabe, Akio; Harada, Teppei; Yoshida, Izumi; Fujita, Kazuhiro; Watai, Masatoshi; Tawata, Shinkichi; Nishikawa, Keisuke; Morimoto, Yoshiki

2016-07-01

Bone homeostasis is maintained by balancing bone formation and bone resorption, but an imbalance between them is associated with various bone-related diseases such as osteoporosis and rheumatoid arthritis. We found that 5,6-dehydrokawain (DK) and dihydro-5,6-dehydrokawain (DDK), which were isolated as promising compounds from Alpinia zerumbet rhizomes, promote differentiation of osteoblastic MC3T3-E1 cells. DK and DDK increased the alkaline phosphatase activity and matrix mineralization of MC3T3-E1 cells. DK exerts larger effects than DDK. The gene expression of runt-related transcription factor 2 and osterix, which are essential transcription factors in the early period of osteoblast differentiation, was significantly increased by DK treatment. The mRNA level of distal-less homeobox 5 was also enhanced by DK treatment, and DK activated the p38 mitogen-activated protein kinase pathway. Therefore, DK may have clinical potential for preventing osteoporosis, and could be considered as a potential anabolic therapeutic agent.

Looking Out From the Top: Differential Effects of Status and Power on Perspective Taking.

PubMed

Blader, Steven L; Shirako, Aiwa; Chen, Ya-Ru

2016-06-01

The impact of hierarchical rank on perspective taking is both practically and theoretically important, prompting considerable research attention to this issue. However, prior research has primarily examined how power affects perspective taking, and has neglected to investigate the impact of status (i.e., the respect and esteem that an individual holds in the eyes of others). Yet status represents a distinct and ubiquitous basis of hierarchical differentiation, one that may profoundly affect perspective taking. The current research addresses this gap, theorizing and testing the prediction that high status enhances perspective taking, in contrast to prior research that has generally found that high power diminishes perspective taking. Five studies, examining various forms of perspective taking across diverse paradigms, provide converging evidence that status and power exert differential effects on perspective taking. Moreover, these studies provide insight regarding the distinction between status and power, as well as the distinct psychology associated with status. © 2016 by the Society for Personality and Social Psychology, Inc.

Organotypic vasculature: From descriptive heterogeneity to functional pathophysiology.

PubMed

Augustin, Hellmut G; Koh, Gou Young

2017-08-25

Blood vessels form one of the body's largest surfaces, serving as a critical interface between the circulation and the different organ environments. They thereby exert gatekeeper functions on tissue homeostasis and adaptation to pathologic challenge. Vascular control of the tissue microenvironment is indispensable in development, hemostasis, inflammation, and metabolism, as well as in cancer and metastasis. This multitude of vascular functions is mediated by organ-specifically differentiated endothelial cells (ECs), whose cellular and molecular heterogeneity has long been recognized. Yet distinct organotypic functional attributes and the molecular mechanisms controlling EC differentiation and vascular bed-specific functions have only become known in recent years. Considering the involvement of vascular dysfunction in numerous chronic and life-threatening diseases, a better molecular understanding of organotypic vasculatures may pave the way toward novel angiotargeted treatments to cure hitherto intractable diseases. This Review summarizes recent progress in the understanding of organotypic vascular differentiation and function. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Increased Differentiation of Dermal Mast Cells in Mice Lacking the Mpl Gene

PubMed Central

Ghinassi, Barbara; Zingariello, Maria; Martelli, Fabrizio; Lorenzini, Rodolfo; Vannucchi, Alessandro M.; Rana, Rosa Alba; Nishikawa, Mitsuo; Migliaccio, Giovanni; Mascarenhas, John

2009-01-01

Thrombopoietin interactions with its receptor, Mpl, play an important role in the regulation of hematopoietic stem/progenitor cell proliferation and differentiation. In this study, we report that the mast cell restricted progenitor cells (MCP) and the mast cell precursors in the bone marrow of wild-type mice express Mpl on their surface. Furthermore, targeted deletion of the Mpl gene in mice decreases the number of MCP while increasing the number of mast cell precursors present in the marrow and spleen. It also increases the number of mast cells present in the dermis, in the peritoneal cavity, and in the gut of the mice. In addition, serosal mast cells from Mplnull mice have a distinctive differentiation profile similar to that expressed by wild-type dermal mast cells. These results suggest that not only does ligation of thrombopoietin with the Mpl receptor exert an effect at the mast cell restricted progenitor cell level, but also plays an unexpected yet important role in mast cell maturation. PMID:19025339

A Single Aplysia Neurotrophin Mediates Synaptic Facilitation via Differentially Processed Isoforms Secreted as Mature or Precursor Forms

PubMed Central

Kassabov, Stefan R.; Choi, Yun-Beom; Karl, Kevin A.; Vishwasrao, Harshad D.; Bailey, Craig H.; Kandel, Eric R.

2014-01-01

Summary Neurotrophins control the development and adult plasticity of the vertebrate nervous system. Failure to identify invertebrate neurotrophin orthologs, however, has precluded studies in invertebrate models, limiting understanding of fundamental aspects of neurotrophin biology and function. We identified a neurotrophin (ApNT) and Trk receptor (ApTrk) in the mollusk Aplysia and find they play a central role in learning related synaptic plasticity. ApNT increases the magnitude and lowers the threshold for induction of long-term facilitation and initiates the growth of new synaptic varicosities at the monosynaptic connection between sensory and motor neurons of the gill-withdrawal reflex. Unlike vertebrate neurotrophins, ApNT has multiple coding exons and exerts distinct synaptic effects through differentially processed and secreted splice isoforms. Our findings demonstrate the existence of bona-fide neurotrophin signaling in invertebrates and reveal a novel, post-transcriptional mechanism, regulating neurotrophin processing and the release of pro- and mature neurotrophins which differentially modulate synaptic plasticity. PMID:23562154

Intracellular calcium levels determine differential modulation of allosteric interactions within G protein-coupled receptor heteromers.

PubMed

Navarro, Gemma; Aguinaga, David; Moreno, Estefania; Hradsky, Johannes; Reddy, Pasham P; Cortés, Antoni; Mallol, Josefa; Casadó, Vicent; Mikhaylova, Marina; Kreutz, Michael R; Lluís, Carme; Canela, Enric I; McCormick, Peter J; Ferré, Sergi

2014-11-20

The pharmacological significance of the adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromer is well established and it is being considered as an important target for the treatment of Parkinson’s disease and other neuropsychiatric disorders. However, the physiological factors that control its distinctive biochemical properties are still unknown. We demonstrate that different intracellular Ca2+ levels exert a differential modulation of A2AR-D2R heteromer-mediated adenylyl-cyclase and MAPK signaling in striatal cells. This depends on the ability of low and high Ca2+ levels to promote a selective interaction of the heteromer with the neuronal Ca2+-binding proteins NCS-1 and calneuron-1, respectively. These Ca2+-binding proteins differentially modulate allosteric interactions within the A2AR-D2R heteromer, which constitutes a unique cellular device that integrates extracellular (adenosine and dopamine) and intracellular (Ca+2) signals to produce a specific functional response.

Wnt inhibition promotes vascular specification of embryonic cardiac progenitors

PubMed Central

Reichman, David E.; Park, Laura; Man, Limor; Redmond, David; Chao, Kenny; Harvey, Richard P.; Taketo, Makoto M.; Rosenwaks, Zev

2018-01-01

ABSTRACT Several studies have demonstrated a multiphasic role for Wnt signaling during embryonic cardiogenesis and developed protocols that enrich for cardiac derivatives during in vitro differentiation of human pluripotent stem cells (hPSCs). However, few studies have investigated the role of Wnt signaling in the specification of cardiac progenitor cells (CPCs) toward downstream fates. Using transgenic mice and hPSCs, we tracked endothelial cells (ECs) that originated from CPCs expressing NKX2.5. Analysis of EC-fated CPCs at discrete phenotypic milestones during hPSC differentiation identified reduced Wnt activity as a hallmark of EC specification, and the enforced activation or inhibition of Wnt reduced or increased, respectively, the degree of vascular commitment within the CPC population during both hPSC differentiation and mouse embryogenesis. Wnt5a, which has been shown to exert an inhibitory influence on Wnt signaling during cardiac development, was dynamically expressed during vascular commitment of hPSC-derived CPCs, and ectopic Wnt5a promoted vascular specification of hPSC-derived and mouse embryonic CPCs. PMID:29217753

Two MCAT elements of the SM alpha-actin promoter function differentially in SM vs. non-SM cells.

PubMed

Swartz, E A; Johnson, A D; Owens, G K

1998-08-01

Transcriptional activity of the smooth muscle (SM) alpha-actin gene is differentially regulated in SM vs. non-SM cells. Contained within the rat SM alpha-actin promoter are two MCAT motifs, binding sites for transcription enhancer factor 1 (TEF-1) transcriptional factors implicated in the regulation of many muscle-specific genes. Transfections of SM alpha-actin promoter-CAT constructs containing wild-type or mutagenized MCAT elements were performed to evaluate their functional significance. Mutation of the MCAT elements resulted in increased transcriptional activity in SM cells, whereas these mutations either had no effect or decreased activity in L6 myotubes or endothelial cells. High-resolution gel shift assays resolved several complexes of different mobilities that were formed between MCAT oligonucleotides and nuclear extracts from the different cell types, although no single band was unique to SM. Western blot analysis of nuclear extracts with polyclonal antibodies to conserved domains of the TEF-1 gene family revealed multiple reactive bands, some that were similar and others that differed between SM and non-SM. Supershift assays with a polyclonal antibody to the TEF-related protein family demonstrated that TEF-1 or TEF-1-related proteins were contained in the shifted complexes. Results suggest that the MCAT elements may contribute to cell type-specific regulation of the SM alpha-actin gene. However, it remains to be determined whether the differential transcriptional activity of MCAT elements in SM vs. non-SM is due to differences in expression of TEF-1 or TEF-1-related proteins or to unique (cell type specific) combinatorial interactions of the MCAT elements with other cis-elements and trans-factors.

Wavelet-based spectral finite element dynamic analysis for an axially moving Timoshenko beam

NASA Astrophysics Data System (ADS)

Mokhtari, Ali; Mirdamadi, Hamid Reza; Ghayour, Mostafa

2017-08-01

In this article, wavelet-based spectral finite element (WSFE) model is formulated for time domain and wave domain dynamic analysis of an axially moving Timoshenko beam subjected to axial pretension. The formulation is similar to conventional FFT-based spectral finite element (SFE) model except that Daubechies wavelet basis functions are used for temporal discretization of the governing partial differential equations into a set of ordinary differential equations. The localized nature of Daubechies wavelet basis functions helps to rule out problems of SFE model due to periodicity assumption, especially during inverse Fourier transformation and back to time domain. The high accuracy of WSFE model is then evaluated by comparing its results with those of conventional finite element and SFE results. The effects of moving beam speed and axial tensile force on vibration and wave characteristics, and static and dynamic stabilities of moving beam are investigated.

Multi-element fingerprinting as a tool in origin authentication of four east China marine species.

PubMed

Guo, Lipan; Gong, Like; Yu, Yanlei; Zhang, Hong

2013-12-01

The contents of 25 elements in 4 types of commercial marine species from the East China Sea were determined by inductively coupled plasma mass spectrometry and atomic absorption spectrometry. The elemental composition was used to differentiate marine species according to geographical origin by multivariate statistical analysis. The results showed that principal component analysis could distinguish samples from different areas and reveal the elements which played the most important role in origin diversity. The established models by partial least squares discriminant analysis (PLS-DA) and by probabilistic neural network (PNN) can both precisely predict the origin of the marine species. Further study indicated that PLS-DA and PNN were efficacious in regional discrimination. The models from these 2 statistical methods, with an accuracy of 97.92% and 100%, respectively, could both distinguish samples from different areas without the need for species differentiation. © 2013 Institute of Food Technologists®

Self-actuating reactor shutdown system

DOEpatents

Barrus, Donald M.; Brummond, Willian A; Peterson, Leslie F.

1988-01-01

A control system for the automatic or self-actuated shutdown or "scram" of a nuclear reactor. The system is capable of initiating scram insertion by a signal from the plant protection system or by independent action directly sensing reactor conditions of low-flow or over-power. Self-actuation due to a loss of reactor coolant flow results from a decrease of pressure differential between the upper and lower ends of an absorber element. When the force due to this differential falls below the weight of the element, the element will fall by gravitational force to scram the reactor. Self-actuation due to high neutron flux is accomplished via a valve controlled by an electromagnet and a thermionic diode. In a reactor over-power, the diode will be heated to a change of state causing the electromagnet to be shorted thereby actuating the valve which provides the changed flow and pressure conditions required for scramming the absorber element.

A Viscoelastic Hybrid Shell Finite Element

NASA Technical Reports Server (NTRS)

Johnson, Arthur

1999-01-01

An elastic large displacement thick-shell hybrid finite element is modified to allow for the calculation of viscoelastic stresses. Internal strain variables are introduced at he element's stress nodes and are employed to construct a viscous material model. First order ordinary differential equations relate the internal strain variables to the corresponding elastic strains at the stress nodes. The viscous stresses are computed from the internal strain variables using viscous moduli which are a fraction of the elastic moduli. The energy dissipated by the action of the viscous stresses in included in the mixed variational functional. Nonlinear quasi-static viscous equilibrium equations are then obtained. Previously developed Taylor expansions of the equilibrium equations are modified to include the viscous terms. A predictor-corrector time marching solution algorithm is employed to solve the algebraic-differential equations. The viscous shell element is employed to numerically simulate a stair-step loading and unloading of an aircraft tire in contact with a frictionless surface.

First- and Second-Order Sensitivity Analysis of a P-Version Finite Element Equation Via Automatic Differentiation

NASA Technical Reports Server (NTRS)

Hou, Gene

1998-01-01

Sensitivity analysis is a technique for determining derivatives of system responses with respect to design parameters. Among many methods available for sensitivity analysis, automatic differentiation has been proven through many applications in fluid dynamics and structural mechanics to be an accurate and easy method for obtaining derivatives. Nevertheless, the method can be computational expensive and can require a high memory space. This project will apply an automatic differentiation tool, ADIFOR, to a p-version finite element code to obtain first- and second- order then-nal derivatives, respectively. The focus of the study is on the implementation process and the performance of the ADIFOR-enhanced codes for sensitivity analysis in terms of memory requirement, computational efficiency, and accuracy.

Exact finite elements for conduction and convection

NASA Technical Reports Server (NTRS)

Thornton, E. A.; Dechaumphai, P.; Tamma, K. K.

1981-01-01

An approach for developing exact one dimensional conduction-convection finite elements is presented. Exact interpolation functions are derived based on solutions to the governing differential equations by employing a nodeless parameter. Exact interpolation functions are presented for combined heat transfer in several solids of different shapes, and for combined heat transfer in a flow passage. Numerical results demonstrate that exact one dimensional elements offer advantages over elements based on approximate interpolation functions.

Method for analyzing soil structure according to the size of structural elements

NASA Astrophysics Data System (ADS)

Wieland, Ralf; Rogasik, Helmut

2015-02-01

The soil structure in situ is the result of cropping history and soil development over time. It can be assessed by the size distribution of soil structural elements such as air-filled macro-pores, aggregates and stones, which are responsible for important water and solute transport processes, gas exchange, and the stability of the soil against compacting and shearing forces exerted by agricultural machinery. A method was developed to detect structural elements of the soil in selected horizontal slices of soil core samples with different soil structures in order for them to be implemented accordingly. In the second step, a fitting tool (Eureqa) based on artificial programming was used to find a general function to describe ordered sets of detected structural elements. It was shown that all the samples obey a hyperbolic function: Y(k) = A /(B + k) , k ∈ { 0 , 1 , 2 , … }. This general behavior can be used to develop a classification method based on parameters {A and B}. An open source software program in Python was developed, which can be downloaded together with a selection of soil samples.

Estrogen Receptors Modulation of Anxiety-Like Behavior

PubMed Central

Borrow, A.P.; Handa, R.J.

2018-01-01

Estrogens exert profound effects on the expression of anxiety in humans and rodents; however, the directionality of these effects varies considerably within both clinical and preclinical literature. It is believed that discrepancies regarding the nature of estrogens’ effects on anxiety are attributable to the differential effects of specific estrogen receptor (ER) subtypes. In this chapter we will discuss the relative impact on anxiety and anxiety-like behavior of each of the three main ERs: ERα, which has a generally anxiogenic effect, ERβ, which has a generally anxiolytic effect, and the G-protein-coupled ER known as GPR30, which has been found to both increase and decrease anxiety-like behavior. In addition, we will describe the known mechanisms by which these receptor subtypes exert their influence on emotional responses, focusing on the hypothalamic–pituitary–adrenal axis and the oxytocinergic and serotonergic systems. The impact of estrogens on the expression of anxiety is likely the result of their combined effects on all of these neurobiological systems. PMID:28061972

New tricks by an old dogma: mechanisms of the Organizational/Activational Hypothesis of steroid-mediated sexual differentiation of brain and behavior.

PubMed

McCarthy, Margaret M; Wright, Christopher L; Schwarz, Jaclyn M

2009-05-01

The hormonal regulation of sexual behavior has been the topic of study for over 50 years and yet controversies persist regarding the importance of early versus late events and the identity of the critical neural and cellular substrates. We have taken a mechanistic approach toward the masculinizing actions of the gonadal steroid estradiol, as a means to understand how organization of the neuroarchitechture during a perinatal sensitive period exerts enduring influences on adult behavior. We have identified important roles for prostaglandins, FAK and paxillin, PI3 kinase and glutamate, and determined that cell-to-cell signaling is a critical component of the early organizational events. We have further determined that the mechanisms mediating different components of sexual behavior are distinct and regionally specific. The multitude of mechanisms by which the steroid estradiol, exerts divergent effects on the developing nervous system provides for a multitude of phenotypes which can vary significantly both within and between the sexes.

New tricks by an old dogma: Mechanisms of the Organizational/Activational Hypothesis of steroid-mediated sexual differentiation of brain and behavior

PubMed Central

McCarthy, Margaret M.; Wright, Christopher L.; Schwarz, Jaclyn M.

2009-01-01

The hormonal regulation of sexual behavior has been the topic of study for over 50 years and yet controversies persist regarding the importance of early versus late events and the identity of the critical neural and cellular substrates. We have taken a mechanistic approach toward the masculinizing actions of the gonadal steroid estradiol, as a means to understand how organization of the neuroarchitechture during a perinatal sensitive period exerts enduring influences on adult behavior. We have identified important roles for prostaglandins, FAK and paxillin, PI3 kinase and glutamate, and determined that cell-to-cell signaling is a critical component of the early organizational events. We have further determined that the mechanisms mediating different components of sexual behavior are distinct and regionally specific. The multitude of mechanisms by which the steroid estradiol, exerts divergent effects on the developing nervous system provides for a multitude of phenotypes which can vary significantly both within and between the sexes. PMID:19682425

Estrogen Receptors Modulation of Anxiety-Like Behavior.

PubMed

Borrow, A P; Handa, R J

2017-01-01

Estrogens exert profound effects on the expression of anxiety in humans and rodents; however, the directionality of these effects varies considerably within both clinical and preclinical literature. It is believed that discrepancies regarding the nature of estrogens' effects on anxiety are attributable to the differential effects of specific estrogen receptor (ER) subtypes. In this chapter we will discuss the relative impact on anxiety and anxiety-like behavior of each of the three main ERs: ERα, which has a generally anxiogenic effect, ERβ, which has a generally anxiolytic effect, and the G-protein-coupled ER known as GPR30, which has been found to both increase and decrease anxiety-like behavior. In addition, we will describe the known mechanisms by which these receptor subtypes exert their influence on emotional responses, focusing on the hypothalamic-pituitary-adrenal axis and the oxytocinergic and serotonergic systems. The impact of estrogens on the expression of anxiety is likely the result of their combined effects on all of these neurobiological systems. © 2017 Elsevier Inc. All rights reserved.

In utero exposure to dioxin causes neocortical dysgenesis through the actions of p27Kip1

PubMed Central

Mitsuhashi, Takayuki; Yonemoto, Junzo; Sone, Hideko; Kosuge, Yasuhiro; Kosaki, Kenjiro; Takahashi, Takao

2010-01-01

Dioxins have been reported to exert various adverse effects, including cell-cycle dysregulation in vitro and impairment of spatial learning and memory after in utero exposure in rodents. Furthermore, children born to mothers who are exposed to dioxin analogs polychlorinated dibenzofurans or polychlorinated biphenyls have developmental impairments in cognitive functions. Here, we show that in utero exposure to dioxins in mice alters differentiation patterns of neural progenitors and leads to decreased numbers of non-GABAergic neurons and thinner deep neocortical layers. This reduction in number of non-GABAergic neurons is assumed to be caused by accumulation of cyclin-dependent kinase inhibitor p27Kip1 in nuclei of neural progenitors. Lending support to this presumption, mice lacking p27Kip1 are not susceptible to in utero dioxin exposure. These results show that environmental pollutants may affect neocortical histogenesis through alterations of functions of specific gene(s)/protein(s) (in our case, dioxins), exerting adverse effects by altering functions of p27Kip1. PMID:20805476

Differentiation Affects the Release of Exosomes from Colon Cancer Cells and Their Ability to Modulate the Behavior of Recipient Cells.

PubMed

Lucchetti, Donatella; Calapà, Federica; Palmieri, Valentina; Fanali, Caterina; Carbone, Federica; Papa, Alfredo; De Maria, Ruggero; De Spirito, Marco; Sgambato, Alessandro

2017-07-01

Exosomes are involved in intercellular communication. We previously reported that sodium butyrate-induced differentiation of HT29 colon cancer cells is associated with a reduced CD133 expression. Herein, we analyzed the role of exosomes in the differentiation of HT29 cells. Exosomes were prepared using ultracentrifugation. Gene expression levels were evaluated by real-time PCR. The cell proliferation rate was assessed by MTT assay and with the electric cell-substrate impedance sensing system, whereas cell motility was assessed using the scratch test and confocal microscopy. Sodium butyrate-induced differentiation of HT29 and Caco-2 cells increased the levels of released exosomes and their expression of CD133. Cell differentiation and the decrease of cellular CD133 expression levels were prevented by blocking multivesicular body maturation. Exosomes released by HT29 differentiating cells carried increased levels of miRNAs, induced an increased proliferation and motility of both colon cancer cells and normal fibroblasts, increased the colony-forming efficiency of cancer cells, and reduced the sodium butyrate-induced differentiation of HT29 cells. Such effects were associated with an increased phosphorylation level of both Src and extracellular signal regulated kinase proteins and with an increased expression of epithelial-to-mesenchymal transition-related genes. Release of exosomes is affected by differentiation of colon cancer cells; exosomes might be used by differentiating cells to get rid of components that are no longer necessary but might continue to exert their effects on recipient cells. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Surveying DNA Elements within Functional Genes of Heterocyst-Forming Cyanobacteria

PubMed Central

Hilton, Jason A.; Meeks, John C.; Zehr, Jonathan P.

2016-01-01

Some cyanobacteria are capable of differentiating a variety of cell types in response to environmental factors. For instance, in low nitrogen conditions, some cyanobacteria form heterocysts, which are specialized for N2 fixation. Many heterocyst-forming cyanobacteria have DNA elements interrupting key N2 fixation genes, elements that are excised during heterocyst differentiation. While the mechanism for the excision of the element has been well-studied, many questions remain regarding the introduction of the elements into the cyanobacterial lineage and whether they have been retained ever since or have been lost and reintroduced. To examine the evolutionary relationships and possible function of DNA sequences that interrupt genes of heterocyst-forming cyanobacteria, we identified and compared 101 interruption element sequences within genes from 38 heterocyst-forming cyanobacterial genomes. The interruption element lengths ranged from about 1 kb (the minimum able to encode the recombinase responsible for element excision), up to nearly 1 Mb. The recombinase gene sequences served as genetic markers that were common across the interruption elements and were used to track element evolution. Elements were found that interrupted 22 different orthologs, only five of which had been previously observed to be interrupted by an element. Most of the newly identified interrupted orthologs encode proteins that have been shown to have heterocyst-specific activity. However, the presence of interruption elements within genes with no known role in N2 fixation, as well as in three non-heterocyst-forming cyanobacteria, indicates that the processes that trigger the excision of elements may not be limited to heterocyst development or that the elements move randomly within genomes. This comprehensive analysis provides the framework to study the history and behavior of these unique sequences, and offers new insight regarding the frequency and persistence of interruption elements in heterocyst-forming cyanobacteria. PMID:27206019

Surveying DNA Elements within Functional Genes of Heterocyst-Forming Cyanobacteria.

PubMed

Hilton, Jason A; Meeks, John C; Zehr, Jonathan P

2016-01-01

Some cyanobacteria are capable of differentiating a variety of cell types in response to environmental factors. For instance, in low nitrogen conditions, some cyanobacteria form heterocysts, which are specialized for N2 fixation. Many heterocyst-forming cyanobacteria have DNA elements interrupting key N2 fixation genes, elements that are excised during heterocyst differentiation. While the mechanism for the excision of the element has been well-studied, many questions remain regarding the introduction of the elements into the cyanobacterial lineage and whether they have been retained ever since or have been lost and reintroduced. To examine the evolutionary relationships and possible function of DNA sequences that interrupt genes of heterocyst-forming cyanobacteria, we identified and compared 101 interruption element sequences within genes from 38 heterocyst-forming cyanobacterial genomes. The interruption element lengths ranged from about 1 kb (the minimum able to encode the recombinase responsible for element excision), up to nearly 1 Mb. The recombinase gene sequences served as genetic markers that were common across the interruption elements and were used to track element evolution. Elements were found that interrupted 22 different orthologs, only five of which had been previously observed to be interrupted by an element. Most of the newly identified interrupted orthologs encode proteins that have been shown to have heterocyst-specific activity. However, the presence of interruption elements within genes with no known role in N2 fixation, as well as in three non-heterocyst-forming cyanobacteria, indicates that the processes that trigger the excision of elements may not be limited to heterocyst development or that the elements move randomly within genomes. This comprehensive analysis provides the framework to study the history and behavior of these unique sequences, and offers new insight regarding the frequency and persistence of interruption elements in heterocyst-forming cyanobacteria.

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

Wen, Li; Wang, Yu; Wang, Huan

Highlights: Black-Right-Pointing-Pointer We detect the functional Ca{sup 2+} currents and mRNA expression of VDCC{sub L} in rMSCs. Black-Right-Pointing-Pointer Blockage of VDCC{sub L} exert antiproliferative and apoptosis-inducing effects on rMSCs. Black-Right-Pointing-Pointer Inhibiting VDCC{sub L} can suppress the ability of rMSCs to differentiate into osteoblasts. Black-Right-Pointing-Pointer {alpha}1C of VDCC{sub L} may be a primary functional subunit in VDCC{sub L}-regulating rMSCs. -- Abstract: L-type voltage-dependent Ca{sup 2+} channels (VDCC{sub L}) play an important role in the maintenance of intracellular calcium homeostasis, and influence multiple cellular processes. They have been confirmed to contribute to the functional activities of osteoblasts. Recently, VDCC{sub L} expression wasmore » reported in mesenchymal stem cells (MSCs), but the role of VDCC{sub L} in MSCs is still undetermined. The aim of this study was to determine whether VDCC{sub L} may be regarded as a new regulator in the proliferation and osteogenic differentiation of rat MSC (rMSCs). In this study, we examined functional Ca{sup 2+} currents (I{sub Ca}) and mRNA expression of VDCC{sub L} in rMSCs, and then suppressed VDCC{sub L} using nifedipine (Nif), a VDCC{sub L} blocker, to investigate its role in rMSCs. The proliferation and osteogenic differentiation of MSCs were analyzed by MTT, flow cytometry, alkaline phosphatase (ALP), Alizarin Red S staining, RT-PCR, and real-time PCR assays. We found that Nif exerts antiproliferative and apoptosis-inducing effects on rMSCs. ALP activity and mineralized nodules were significantly decreased after Nif treatment. Moreover, the mRNA levels of the osteogenic markers, osteocalcin (OCN), bone sialoprotein (BSP), and runt-related transcription factor 2 (Runx2), were also down-regulated. In addition, we transfected {alpha}1C-siRNA into the cells to further confirm the role of VDCC{sub L} in rMSCs, and a similar effect on osteogenesis was found. These results suggest that VDCC{sub L} plays a crucial role in the proliferation and osteogenic differentiation of rMSCs.« less

Phospho1 deficiency transiently modifies bone architecture yet produces consistent modification in osteocyte differentiation and vascular porosity with ageing

PubMed Central

Javaheri, B.; Carriero, A.; Staines, K.A.; Chang, Y.-M.; Houston, D.A.; Oldknow, K.J.; Millan, J.L.; Kazeruni, Bassir N.; Salmon, P.; Shefelbine, S.; Farquharson, C.; Pitsillides, A.A.

2015-01-01

PHOSPHO1 is one of principal proteins involved in initiating bone matrix mineralisation. Recent studies have found that Phospho1 KO mice (Phospho1-R74X) display multiple skeletal abnormalities with spontaneous fractures, bowed long bones, osteomalacia and scoliosis. These analyses have however been limited to young mice and it remains unclear whether the role of PHOSPHO1 is conserved in the mature murine skeleton where bone turnover is limited. In this study, we have used ex-vivo computerised tomography to examine the effect of Phospho1 deletion on tibial bone architecture in mice at a range of ages (5, 7, 16 and 34 weeks of age) to establish whether its role is conserved during skeletal growth and maturation. Matrix mineralisation has also been reported to influence terminal osteoblast differentiation into osteocytes and we have also explored whether hypomineralised bones in Phospho1 KO mice exhibit modified osteocyte lacunar and vascular porosity. Our data reveal that Phospho1 deficiency generates age-related defects in trabecular architecture and compromised cortical microarchitecture with greater porosity accompanied by marked alterations in osteocyte shape, significant increases in osteocytic lacuna and vessel number. Our in vitro studies examining the behaviour of osteoblast derived from Phospho1 KO and wild-type mice reveal reduced levels of matrix mineralisation and modified osteocytogenic programming in cells deficient in PHOSPHO1. Together our data suggest that deficiency in PHOSPHO1 exerts modifications in bone architecture that are transient and depend upon age, yet produces consistent modification in lacunar and vascular porosity. It is possible that the inhibitory role of PHOSPHO1 on osteocyte differentiation leads to these age-related changes in bone architecture. It is also intriguing to note that this apparent acceleration in osteocyte differentiation evident in the hypomineralised bones of Phospho1 KO mice suggests an uncoupling of the interplay between osteocytogenesis and biomineralisation. Further studies are required to dissect the molecular processes underlying the regulatory influences exerted by PHOSPHO1 on the skeleton with ageing. PMID:26232374

Immunogenicity and immunomodulatory properties of hepatocyte-like cells derived from human amniotic epithelial cells.

PubMed

Tee, Jing Yang; Vaghjiani, Vijesh; Liu, Yu Han; Murthi, Padma; Chan, James; Manuelpillai, Ursula

2013-01-01

Hepatocyte transplantation is being trialled as an alternative to whole organ transplant for patients with acute liver failure and liver specific metabolic diseases. Due to the scarcity of human hepatocytes, hepatocyte-like cells (HLC) generated from stem cells may become a viable alternative to hepatocyte transplantation. Human amniotic epithelial cells (hAEC) from the placenta have stem cell-like properties and can be differentiated into HLC. Naïve hAEC have low immunogenicity and exert immunomodulatory effects that may facilitate allogeneic transplantation. However, whether the immunogenicity and immunomodulatory properties alter with differentiation into HLC are unknown. We further characterized HLC generated from hAEC, examined changes in human leucocyte antigens (HLA) and co-stimulatory molecules and effects exerted by the HLC on human peripheral blood mononuclear cells (PBMC). HLC derived from hAEC expressed proteins found in hepatocytes, had CYP3A4 drug metabolizing enzyme activity and secreted urea. IFN-γ treatment increased HLA Class IA, Class II and co-stimulatory molecule CD40 expression in the HLC. IFN-γ treated HLC stimulated proliferation of PBMC in one-way mixed lymphocyte reactions and were more immunogenic than undifferentiated hAEC. However, the HLC showed immunomodulatory properties and inhibited mitogen induced PBMC proliferation in vitro. PBMC proliferation may have been inhibited by IL-6, TGF-β1, PGE2 and HLA-G secreted by the HLC. The retention of immunomodulatory properties may enable HLC grafts to survive for longer periods despite the immunogenicity of the HLC.

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

Xiao, Fei; Zhai, Zanjing; Jiang, Chuan

Wear particle-induced osteolysis and subsequent aseptic loosening remains the most common complication that limits the longevity of prostheses. Wear particle-induced osteoclastogenesis is known to be responsible for extensive bone erosion that leads to prosthesis failure. Thus, inhibition of osteoclastic bone resorption may serve as a therapeutic strategy for the treatment of wear particle induced osteolysis. In this study, we demonstrated for the first time that geraniin, an active natural compound derived from Geranium thunbergii, ameliorated particle-induced osteolysis in a Ti particle-induced mouse calvaria model in vivo. We also investigated the mechanism by which geraniin exerts inhibitory effects on osteoclasts. Geraniinmore » inhibited RANKL-induced osteoclastogenesis in a dose-dependent manner, evidenced by reduced osteoclast formation and suppressed osteoclast specific gene expression. Specially, geraniin inhibited actin ring formation and bone resorption in vitro. Further molecular investigation demonstrated geraniin impaired osteoclast differentiation via the inhibition of the RANKL-induced NF-κB and ERK signaling pathways, as well as suppressed the expression of key osteoclast transcriptional factors NFATc1 and c-Fos. Collectively, our data suggested that geraniin exerts inhibitory effects on osteoclast differentiation in vitro and suppresses Ti particle-induced osteolysis in vivo. Geraniin is therefore a potential natural compound for the treatment of wear particle induced osteolysis in prostheses failure. - Highlights: • Geraniin suppresses osteoclasts formation and function in vitro. • Geraniin impairs RANKL-induced nuclear factor-κB and ERK signaling pathway. • Geraniin suppresses osteolysis in vivo. • Geraniin may be used for treating osteoclast related diseases.« less

Paracrine control of vascularization and neurogenesis by neurotrophins.

PubMed

Emanueli, Costanza; Schratzberger, Peter; Kirchmair, Rudolf; Madeddu, Paolo

2003-10-01

The neuronal system plays a fundamental role in the maturation of primitive embryonic vascular network by providing a paracrine template for blood vessel branching and arterial differentiation. Furthermore, postnatal vascular and neural regeneration cooperate in the healing of damaged tissue. Neurogenesis continues in adulthood although confined to specific brain regions. Following ischaemic insult, neural staminal cells contribute towards the healing process through the stimulation of neurogenesis and vasculogenesis. Evidence indicates that nerves and blood vessels exert a reciprocal control of their own growth by paracrine mechanisms. For instance, guidance factors, including vascular endothelial growth factor A (VEGF-A) and semaphorins, which share the ability of binding neuropilin receptors, play a pivotal role in the tridimensional growth pattern of arterial vessels and nerves. Animal models and clinical studies have demonstrated a role of VEGF-A in the pathogenesis of ischaemic and diabetic neuropathies. Further, supplementation with VEGF-A ameliorates neuronal recovery by exerting protective effects on nerves and stimulating reparative neovascularization. Human tissue kallikrein, a recently discovered angiogenic and arteriogenic factor, accelerates neuronal recovery by stimulating the growth of vasa nervorum. Conversely, the neurotrophin nerve growth factor, known to regulate neuronal survival and differentiation, is now regarded as a stimulator of angiogenesis and arteriogenesis. These results indicate that angiogenesis and neurogenesis are paracrinally regulated by growth factors released by endothelial cells and neurons. Supplementation of these growth factors, alone or in combination, could benefit the treatment of ischaemic diseases and neuropathies.

Variation in functional responses to water stress and differentiation between natural allopolyploid populations in the Brachypodium distachyon species complex.

PubMed

Martínez, Luisa M; Fernández-Ocaña, Ana; Rey, Pedro J; Salido, Teresa; Amil-Ruiz, Francisco; Manzaneda, Antonio J

2018-06-08

Some polyploid species show enhanced physiological tolerance to drought compared with their progenitors. However, very few studies have examined the consistency of physiological drought response between genetically differentiated natural polyploid populations, which is key to evaluation of the importance of adaptive evolution after polyploidization in those systems where drought exerts a selective pressure. A comparative functional approach was used to investigate differentiation of drought-tolerance-related traits in the Brachypodium species complex, a model system for grass polyploid adaptive speciation and functional genomics that comprises three closely related annual species: the two diploid parents, B. distachyon and B. stacei, and the allotetraploid derived from them, B. hybridum. Differentiation of drought-tolerance-related traits between ten genetically distinct B. hybridum populations and its ecological correlates was further analysed. The functional drought response is overall well differentiated between Brachypodium species. Brachypodium hybridum allotetraploids showed a transgressive expression pattern in leaf phytohormone content in response to drought. In contrast, other B. hybridum physiological traits correlated to B. stacei ones. Particularly, proline and water content were the traits that best discriminated these species from B. distachyon under drought. After polyploid formation and/or colonization, B. hybridum populations have adaptively diverged physiologically and genetically in response to variations in aridity.

Vitamin C-linker-conjugated tripeptide AHK stimulates BMP-2-induced osteogenic differentiation of mouse myoblast C2C12 cells.

PubMed

Jung, Jung-Il; Park, Kyeong-Yong; Lee, Yura; Park, Mira; Kim, Jiyeon

Vitamin C-linker-conjugated Ala-His-Lys tripeptide (Vit C-AHK) is a derivative of Vitamin C-conjugated tripeptides, which were originally developed as a component of a product for collagen synthesis enhancement or human dermal fibroblast growth. Here, we investigated the effect of Vit C-AHK on bone morphogenetic protein (BMP)-2-induced osteoblast differentiation in a cell culture model. Vit C-AHK enhanced proliferation of C2C12 cells and induction of BMP-2-induced alkaline phosphatase, a typical marker of osteoblast differentiation. Vit C-AHK also stimulated the phosphorylation and translocation of Smad1/5/8 to the nucleus and phosphorylation of mitogen-activated protein kinases (MAPKs) including ERK1/2 and p38. In addition, Vit C-AHK enhanced the BMP-2-induced mRNA expression of osteoblast differentiation-related genes such as ALP, BMP-2, Osteocalcin, and Runx2. Our results suggest that Vit C-AHK exerts an enhancing effect on osteoblast proliferation and differentiation through activation of Smad1/5/8 and MAPK ERK1/2 and p38 signaling and without significant cytotoxicity. These results provide important data for the development of peptide-based bone-regenerative agents and treatment of bone-related disorders. Copyright © 2018 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

DNA-damage-induced differentiation of leukaemic cells as an anti-cancer barrier.

PubMed

Santos, Margarida A; Faryabi, Robert B; Ergen, Aysegul V; Day, Amanda M; Malhowski, Amy; Canela, Andres; Onozawa, Masahiro; Lee, Ji-Eun; Callen, Elsa; Gutierrez-Martinez, Paula; Chen, Hua-Tang; Wong, Nancy; Finkel, Nadia; Deshpande, Aniruddha; Sharrow, Susan; Rossi, Derrick J; Ito, Keisuke; Ge, Kai; Aplan, Peter D; Armstrong, Scott A; Nussenzweig, André

2014-10-02

Self-renewal is the hallmark feature both of normal stem cells and cancer stem cells. Since the regenerative capacity of normal haematopoietic stem cells is limited by the accumulation of reactive oxygen species and DNA double-strand breaks, we speculated that DNA damage might also constrain leukaemic self-renewal and malignant haematopoiesis. Here we show that the histone methyl-transferase MLL4, a suppressor of B-cell lymphoma, is required for stem-cell activity and an aggressive form of acute myeloid leukaemia harbouring the MLL-AF9 oncogene. Deletion of MLL4 enhances myelopoiesis and myeloid differentiation of leukaemic blasts, which protects mice from death related to acute myeloid leukaemia. MLL4 exerts its function by regulating transcriptional programs associated with the antioxidant response. Addition of reactive oxygen species scavengers or ectopic expression of FOXO3 protects MLL4(-/-) MLL-AF9 cells from DNA damage and inhibits myeloid maturation. Similar to MLL4 deficiency, loss of ATM or BRCA1 sensitizes transformed cells to differentiation, suggesting that myeloid differentiation is promoted by loss of genome integrity. Indeed, we show that restriction-enzyme-induced double-strand breaks are sufficient to induce differentiation of MLL-AF9 blasts, which requires cyclin-dependent kinase inhibitor p21(Cip1) (Cdkn1a) activity. In summary, we have uncovered an unexpected tumour-promoting role of genome guardians in enforcing the oncogene-induced differentiation blockade in acute myeloid leukaemia.

Interpreting HSE Contents of Planetary Basalts: The Importance of Sulfide Saturation and Under-Saturation

NASA Technical Reports Server (NTRS)

Righter, K.

2000-01-01

Highly siderophile elements provide important constraints on planetary differentiation due to their siderophile behavior. Their interpretation in terms of planetary differentiation models has so far overlooked the importance of sulfide saturation and under-saturation.

HOXC9-Induced Differentiation in Neuroblastoma Development

DTIC Science & Technology

2014-10-01

Neuroblastoma Development PRINCIPAL INVESTIGATOR: Han-Fei Ding RECIPIENT: Georgia Health Sciences University Research Institute, Inc... Neuroblastoma  Development   5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0613 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...role in determining the differentiation states of neuroblastoma tumors, with higher levels of HOXC9 promoting differentiation. At the cellular level

Understanding the Impact of Organizational Differentiation in High-Poverty Schools with Alternative Models of Title I Service Delivery.

ERIC Educational Resources Information Center

Meyer, Stephen J.

American public schools historically have used a range of differentiating mechanisms to meet the needs of diverse groups of students. Examples from Title I service delivery include pullout, in-class, add-on, and replacement programs. These models have elements that differentiate the educational experience of Title I students to varying degrees and…

Peridynamic Multiscale Finite Element Methods

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

Costa, Timothy; Bond, Stephen D.; Littlewood, David John

The problem of computing quantum-accurate design-scale solutions to mechanics problems is rich with applications and serves as the background to modern multiscale science research. The prob- lem can be broken into component problems comprised of communicating across adjacent scales, which when strung together create a pipeline for information to travel from quantum scales to design scales. Traditionally, this involves connections between a) quantum electronic structure calculations and molecular dynamics and between b) molecular dynamics and local partial differ- ential equation models at the design scale. The second step, b), is particularly challenging since the appropriate scales of molecular dynamic andmore » local partial differential equation models do not overlap. The peridynamic model for continuum mechanics provides an advantage in this endeavor, as the basic equations of peridynamics are valid at a wide range of scales limiting from the classical partial differential equation models valid at the design scale to the scale of molecular dynamics. In this work we focus on the development of multiscale finite element methods for the peridynamic model, in an effort to create a mathematically consistent channel for microscale information to travel from the upper limits of the molecular dynamics scale to the design scale. In particular, we first develop a Nonlocal Multiscale Finite Element Method which solves the peridynamic model at multiple scales to include microscale information at the coarse-scale. We then consider a method that solves a fine-scale peridynamic model to build element-support basis functions for a coarse- scale local partial differential equation model, called the Mixed Locality Multiscale Finite Element Method. Given decades of research and development into finite element codes for the local partial differential equation models of continuum mechanics there is a strong desire to couple local and nonlocal models to leverage the speed and state of the art of local models with the flexibility and accuracy of the nonlocal peridynamic model. In the mixed locality method this coupling occurs across scales, so that the nonlocal model can be used to communicate material heterogeneity at scales inappropriate to local partial differential equation models. Additionally, the computational burden of the weak form of the peridynamic model is reduced dramatically by only requiring that the model be solved on local patches of the simulation domain which may be computed in parallel, taking advantage of the heterogeneous nature of next generation computing platforms. Addition- ally, we present a novel Galerkin framework, the 'Ambulant Galerkin Method', which represents a first step towards a unified mathematical analysis of local and nonlocal multiscale finite element methods, and whose future extension will allow the analysis of multiscale finite element methods that mix models across scales under certain assumptions of the consistency of those models.« less

Carbon and sulfur budget of the silicate Earth explained by accretion of differentiated planetary embryos

NASA Astrophysics Data System (ADS)

Li, Yuan; Dasgupta, Rajdeep; Tsuno, Kyusei; Monteleone, Brian; Shimizu, Nobumichi

2016-10-01

The abundances of volatile elements in the Earth's mantle have been attributed to the delivery of volatile-rich material after the main phase of accretion. However, no known meteorites could deliver the volatile elements, such as carbon, nitrogen, hydrogen and sulfur, at the relative abundances observed for the silicate Earth. Alternatively, Earth could have acquired its volatile inventory during accretion and differentiation, but the fate of volatile elements during core formation is known only for a limited set of conditions. Here we present constraints from laboratory experiments on the partitioning of carbon and sulfur between metallic cores and silicate mantles under conditions relevant for rocky planetary bodies. We find that carbon remains more siderophile than sulfur over a range of oxygen fugacities; however, our experiments suggest that in reduced or sulfur-rich bodies, carbon is expelled from the segregating core. Combined with previous constraints, we propose that the ratio of carbon to sulfur in the silicate Earth could have been established by differentiation of a planetary embryo that was then accreted to the proto-Earth. We suggest that the accretion of a Mercury-like (reduced) or a sulfur-rich (oxidized) differentiated body--in which carbon has been preferentially partitioned into the mantle--may explain the Earth's carbon and sulfur budgets.

Recent Development of Multigrid Algorithms for Mixed and Noncomforming Methods for Second Order Elliptical Problems

NASA Technical Reports Server (NTRS)

Chen, Zhangxin; Ewing, Richard E.

1996-01-01

Multigrid algorithms for nonconforming and mixed finite element methods for second order elliptic problems on triangular and rectangular finite elements are considered. The construction of several coarse-to-fine intergrid transfer operators for nonconforming multigrid algorithms is discussed. The equivalence between the nonconforming and mixed finite element methods with and without projection of the coefficient of the differential problems into finite element spaces is described.

Requirement for ErbB2/ErbB signaling in developing cartilage and bone.

PubMed

Fisher, Melanie C; Clinton, Gail M; Maihle, Nita J; Dealy, Caroline N

2007-08-01

During endochondral ossification, the skeletal elements of vertebrate limbs form and elongate via coordinated control of chondrocyte and osteoblast differentiation and proliferation. The role of signaling by the ErbB family of receptor tyrosine kinases, which consists of ErbB1 (epidermal growth factor receptor or EGFR), ErbB2, ErbB3 and ErbB4, has been little studied during cartilage and bone development. Signaling by the ErbB network generates a diverse array of cellular responses via formation of ErbB dimers activated by distinct ligands that produce distinct signal outputs. Herstatin is a soluble ErbB2 receptor that acts in a dominant negative fashion to inhibit ErbB signaling by binding to endogenous ErbB receptors, preventing functional dimer formation. Here, we examine the effects of Herstatin on limb skeletal element development in transgenic mice, achieved via Prx1 promoter-driven expression in limb cartilage and bone. The limb skeletal elements of Prx1-Herstatin embryos are shortened, and chondrocyte maturation and osteoblast differentiation are delayed. In addition, proliferation by chondrocytes and periosteal cells of Prx1-Herstatin limb skeletal elements is markedly reduced. Our study identifies requirements for ErbB signaling in the maintenance of chondrocyte and osteoblast proliferation involved in the timely progression of chondrocyte maturation and periosteal osteoblast differentiation.

Inhibition of TGF-β Signaling in SHED Enhances Endothelial Differentiation.

PubMed

Xu, J G; Gong, T; Wang, Y Y; Zou, T; Heng, B C; Yang, Y Q; Zhang, C F

2018-02-01

Low efficiency of deriving endothelial cells (ECs) from adult stem cells hampers their utilization in tissue engineering studies. The purpose of this study was to investigate whether suppression of transforming growth factor beta (TGF-β) signaling could enhance the differentiation efficiency of dental pulp-derived stem cells into ECs. We initially used vascular endothelial growth factor A (VEGF-A) to stimulate 2 dental pulp-derived stem cells (dental pulp stem cells and stem cells from human exfoliated deciduous teeth [SHED]) and compared their differentiation capacity into ECs. We further evaluated whether the vascular endothelial growth factor receptor I (VEGF-RI)-specific ligand placental growth factor-1 (PlGF-1) could mediate endothelial differentiation. Finally, we investigated whether the TGF-β signaling inhibitor SB-431542 could enhance the inductive effect of VEGF-A on endothelial differentiation, as well as the underlying mechanisms involved. ECs differentiated from dental pulp-derived stem cells exhibited the typical phenotypes of primary ECs, with SHED possessing a higher endothelial differentiation potential than dental pulp stem cells. VEGFR1-specific ligand-PLGF exerted a negligible effect on SHED-ECs differentiation. Compared with VEGF-A alone, the combination of VEGF-A and SB-431542 significantly enhanced the endothelial differentiation of SHED. The presence of SB-431542 inhibited the phosphorylation of Suppressor of Mothers Against Decapentaplegic 2/3 (SMAD2/3), allowing for VEGF-A-dependent phosphorylation and upregulation of VEGFR2. Our results indicate that the combination of VEGF-A and SB-431542 could enhance the differentiation of dental pulp-derived stem cells into endothelial cells, and this process is mediated through enhancement of VEGF-A-VEGFR2 signaling and concomitant inhibition of TGF-β-SMAD2/3 signaling.

Knowledge Distance, Cognitive-Search Processes, and Creativity

PubMed Central

Acar, Oguz Ali; van den Ende, Jan

2016-01-01

Prior research has provided conflicting arguments and evidence about whether people who are outsiders or insiders relative to a knowledge domain are more likely to demonstrate scientific creativity in that particular domain. We propose that the nature of the relationship between creativity and the distance of an individual’s expertise from a knowledge domain depends on his or her cognitive processes of problem solving (i.e., cognitive-search effort and cognitive-search variation). In an analysis of 230 solutions generated in a science contest platform, we found that distance was positively associated with creativity when problem solvers engaged in a focused search (i.e., low cognitive-search variation) and exerted a high level of cognitive effort. People whose expertise was close to a knowledge domain, however, were more likely to demonstrate creativity in that domain when they drew on a wide variety of different knowledge elements for recombination (i.e., high cognitive-search variation) and exerted substantial cognitive effort. PMID:27016241

Knowledge Distance, Cognitive-Search Processes, and Creativity: The Making of Winning Solutions in Science Contests.

PubMed

Acar, Oguz Ali; van den Ende, Jan

2016-05-01

Prior research has provided conflicting arguments and evidence about whether people who are outsiders or insiders relative to a knowledge domain are more likely to demonstrate scientific creativity in that particular domain. We propose that the nature of the relationship between creativity and the distance of an individual's expertise from a knowledge domain depends on his or her cognitive processes of problem solving (i.e., cognitive-search effort and cognitive-search variation). In an analysis of 230 solutions generated in a science contest platform, we found that distance was positively associated with creativity when problem solvers engaged in a focused search (i.e., low cognitive-search variation) and exerted a high level of cognitive effort. People whose expertise was close to a knowledge domain, however, were more likely to demonstrate creativity in that domain when they drew on a wide variety of different knowledge elements for recombination (i.e., high cognitive-search variation) and exerted substantial cognitive effort. © The Author(s) 2016.

Capillary forces exerted by liquid drops caught between crossed cylinders. A 3-D meniscus problem with free contact line

NASA Technical Reports Server (NTRS)

Patzek, T. W.; Scriven, L. E.

1982-01-01

The Young-Laplace equation is solved for three-dimensional menisci between crossed cylinders, with either the contact line fixed or the contact angle prescribed, by means of the Galerkin/finite element method. Shapes are computed, and with them the practically important quantities: drop volume, wetted area, capillary pressure force, surface tension force, and the total force exerted by the drop on each cylinder. The results show that total capillary force between cylinders increases with decreasing contact angle, i.e. with better wetting. Capillary force is also increases with decreasing drop volume, approaching an asymptotic limit. However, the wetted area on each cylinder decreases with decreasing drop volume, which raises the question of the optimum drop volume to strive for, when permanent bonding is sought from solidified liquid. For then the strength of the bond is likely to depend upon the area of contact, which is the wetted area when the bonding agent was introduced in liquid form.

Expression of Mutant Human DISC1 in Mice Supports Abnormalities in Differentiation of Oligodendrocytes

PubMed Central

Katsel, Pavel; Tan, Weilun; Abazyan, Bagrat; Davis, Kenneth L; Ross, Christopher; Pletnikov, Mikhail V; Haroutunian, Vahram

2011-01-01

Abnormalities in oligodendrocyte (OLG) differentiation and OLG gene expression deficit have been described in schizophrenia (SZ). Recent studies revealed a critical requirement for Disrupted-in-Schizophrenia 1 (DISC1) in neural development. Transgenic mice with forebrain restricted expression of mutant human DISC1 (ΔhDISC1) are characterized by neuroanatomical and behavioral abnormalities reminiscent of some features of SZ. We sought to determine whether the expression of ΔhDISC1 may influence the development of OLGs in this mouse model. OLG- and cell cycle-associated gene and protein expression were characterized in the forebrain of ΔhDISC1 mice during different stages of neurodevelopment (E15 and P1 days) and in adulthood. The results suggest that the expression of ΔhDISC1 exerts a significant influence on oligodendrocyte differentiation and function, evidenced by premature OLG differentiation and increased proliferation of their progenitors. Additional findings showed that neuregulin 1 and its receptors may be contributing factors to the observed upregulation of OLG genes. Thus, OLG function may be perturbed by mutant hDISC1 in a model system that provides new avenues for studying aspects of the pathogenesis of SZ. PMID:21605958

Concurrent Schedules of Positive and Negative Reinforcement: Differential-Impact and Differential-Outcomes Hypotheses

PubMed Central

Magoon, Michael A; Critchfield, Thomas S

2008-01-01

Considerable evidence from outside of operant psychology suggests that aversive events exert greater influence over behavior than equal-sized positive-reinforcement events. Operant theory is largely moot on this point, and most operant research is uninformative because of a scaling problem that prevents aversive events and those based on positive reinforcement from being directly compared. In the present investigation, humans' mouse-click responses were maintained on similarly structured, concurrent schedules of positive (money gain) and negative (avoidance of money loss) reinforcement. Because gains and losses were of equal magnitude, according to the analytical conventions of the generalized matching law, bias (log b ≠ 0) would indicate differential impact by one type of consequence; however, no systematic bias was observed. Further research is needed to reconcile this outcome with apparently robust findings in other literatures of superior behavior control by aversive events. In an incidental finding, the linear function relating log behavior ratio and log reinforcement ratio was steeper for concurrent negative and positive reinforcement than for control conditions involving concurrent positive reinforcement. This may represent the first empirical confirmation of a free-operant differential-outcomes effect predicted by contingency-discriminability theories of choice. PMID:18683609

Spatial and temporal regulation of the forisome gene for1 in the phloem during plant development.

PubMed

Noll, Gundula A; Fontanellaz, Maria E; Rüping, Boris; Ashoub, Ahmed; van Bel, Aart J E; Fischer, Rainer; Knoblauch, Michael; Prüfer, Dirk

2007-10-01

Forisomes are protein aggregates found uniquely in the sieve elements of Fabaceaen plants. Upon wounding they undergo a reversible, calcium-dependent conformational switch which enables them to act as cellular stopcocks. Forisomes begin to form in young sieve elements at an early stage of metaphloem differentiation. Genes encoding forisome components could therefore be useful as markers of early sieve element development. Here we present a comprehensive analysis of the developmental expression profile of for1, which encodes such a forisome component. The for1 gene is highly conserved among Fabaceaen species and appears to be unique to this phylogenetic lineage since no orthologous genes have been found in other plants, including Arabidopsis and rice. Even so, transgenic tobacco plants expressing reporter genes under the control of the for1 promoter display reporter activity exclusively in immature sieve elements. This suggests that the regulation of sieve element development is highly conserved even in plants where mature forisomes have not been detected. The promoter system could therefore provide a powerful tool for the detailed analysis of differentiation in metaphloem sieve elements in an unexpectedly broad range of plant species.

Sharing leadership influence: a life-cycle model.

PubMed

Hunt, E H; Sleeth, R G

1977-07-01

We have described the effective leader in terms of several concepts: (1) leadership style as a means of sharing the influence of leadership with a ready group; (2) the readiness of a group to successfully exert influence on the practice; (3) the matching of leadership styles with group readiness; and (4) the impact of the environment on the readiness of a group. We have described how all of these elements combine to determine a leader's effectiveness. All elements interact and present the leader with a situation for which he must adopt an appropriate leadership style (Table 1). Several elements combine to change the readiness of a group through four phases - unready, ready, mature, and professional. The leader then matches leadership styles I through IV to these levels of readiness. We believe a dentist will be effective as a leader in proportion to his success in matching an appropriate leadership style to the readiness of his group to perform in its particular environment.

Fighting Viral Infections and Virus-Driven Tumors with Cytotoxic CD4+ T Cells

PubMed Central

Muraro, Elena; Merlo, Anna; Martorelli, Debora; Cangemi, Michela; Dalla Santa, Silvia; Dolcetti, Riccardo; Rosato, Antonio

2017-01-01

CD4+ T cells have been and are still largely regarded as the orchestrators of immune responses, being able to differentiate into distinct T helper cell populations based on differentiation signals, transcription factor expression, cytokine secretion, and specific functions. Nonetheless, a growing body of evidence indicates that CD4+ T cells can also exert a direct effector activity, which depends on intrinsic cytotoxic properties acquired and carried out along with the evolution of several pathogenic infections. The relevant role of CD4+ T cell lytic features in the control of such infectious conditions also leads to their exploitation as a new immunotherapeutic approach. This review aims at summarizing currently available data about functional and therapeutic relevance of cytotoxic CD4+ T cells in the context of viral infections and virus-driven tumors. PMID:28289418

Promiscuous Actions of Small Molecule Inhibitors of the Protein Kinase D-Class IIa HDAC Axis in Striated Muscle

PubMed Central

Lemon, Douglas D.; Harrison, Brooke C.; Horn, Todd R.; Stratton, Matthew S.; Ferguson, Bradley S.; Wempe, Michael F.; McKinsey, Timothy A.

2015-01-01

PKD-mediated phosphorylation of class IIa HDACs frees the MEF2 transcription factor to activate genes that govern muscle differentiation and growth. Studies of the regulation and function of this signaling axis have involved MC1568 and Gö-6976, which are small molecule inhibitors of class IIa HDAC and PKD catalytic activity, respectively. We describe unanticipated effects of these compounds. MC1568 failed to inhibit class IIa HDAC catalytic activity in vitro, and exerted divergent effects on skeletal muscle differentiation compared to a bona fide inhibitor of these HDACs. In cardiomyocytes, Gö-6976 triggered calcium signaling and activated stress-inducible kinases. Based on these findings, caution is warranted when employing MC1568 and Gö-6976 as pharmacological tool compounds to assess functions of class IIa HDACs and PKD. PMID:25816750

Physical correction filter for improving the optical quality of an image

NASA Technical Reports Server (NTRS)

Lee, S. Y. (Inventor)

1975-01-01

A family of physical correction filters is described. Each filter is designed to correct image content of a photographed scene of limited resolution and includes a first filter element with a pinhole through which light passes to a differential amplifier. A second filter element through which light passes through one or more openings, whose geometric configuration is a function of the cause of the resolution loss included. The light, passing through the second filter element, is also supplied to the differential amplifier whose output is used to activate an optical display or recorder to reproduce a photograph or display of the scene in the original photograph or display of the scene in the original photograph with resolution which is significantly greater than that characterizing the original photograph.

Rare earths and other trace elements in Apollo 14 samples.

NASA Technical Reports Server (NTRS)

Helmke, P. A.; Haskin, L. A.; Korotev, R. L.; Ziege, K. E.

1972-01-01

REE and other trace elements have been determined in igneous rocks 14053, 14072, and 14310, in breccias 14063 and 14313, and in fines 14163. All materials analyzed have typical depletions of Eu except for feldspar fragments from the breccias and igneous fragments from 14063. Igneous rocks 14072 and 14053 have REE concentrations very similar to Apollo 12 basalts; 14310 has the highest REE concentrations yet observed for a large fragment of lunar basalt. The effects of crystallization of a basaltic liquid as a closed system on the concentrations of Sm and Eu in feldspar are considered. Small anorthositic fragments may have originated by simple crystallization from very highly differentiated basalt (KREEP) or by closed-system crystallization in a less differentiated starting material. Application of independent models of igneous differentiation to Sm and Eu in massive anorthosite 15415 and to Sm and Eu in lunar basalts suggests a common starting material with a ratio of concentrations of Sm and Eu about the same as that in chondrites and with concentrations of those elements about 15 times enriched over chondrites.

Control device for prosthetic urinary sphincter cuff

NASA Technical Reports Server (NTRS)

Reinicke, Robert H. (Inventor)

1983-01-01

A device for controlling flow of fluid to and from a resilient inflatable cuff implanted about the urethra to control flow of urine therethrough. The device comprises a flexible bulb reservoir and a control unit that includes a manually operated valve that opens automatically when the bulb is squeezed to force fluid into the cuff for closing the urethra. The control unit also includes a movable valve seat member having a relatively large area exposed to pressure of fluid in a chamber that is connected to the cuff and which moves to a position in which the valve member is unseated by an abutment when fluid pressure in the chamber exceeds a predetermined value to thereby relieve excess fluid pressure in the cuff. The arrangement is such that the valve element is held closed against the seat member by the full differential in fluid pressures acting on both sides of the valve element until the seat member is moved away from the valve element to thus insure positive closing of the valve element until the seat member is moved out of engagement with the valve element by excess pressure differential.

Double-layer rotor magnetic shield performance analysis in high temperature superconducting synchronous generators under short circuit fault conditions

NASA Astrophysics Data System (ADS)

Hekmati, Arsalan; Aliahmadi, Mehdi

2016-12-01

High temperature superconducting, HTS, synchronous machines benefit from a rotor magnetic shield in order to protect superconducting coils against asynchronous magnetic fields. This magnetic shield, however, suffers from exerted Lorentz forces generated in light of induced eddy currents during transient conditions, e.g. stator windings short-circuit fault. In addition, to the exerted electromagnetic forces, eddy current losses and the associated effects on the cryogenic system are the other consequences of shielding HTS coils. This study aims at investigating the Rotor Magnetic Shield, RMS, performance in HTS synchronous generators under stator winding short-circuit fault conditions. The induced eddy currents in different circumferential positions of the rotor magnetic shield along with associated Joule heating losses would be studied using 2-D time-stepping Finite Element Analysis, FEA. The investigation of Lorentz forces exerted on the magnetic shield during transient conditions has also been performed in this paper. The obtained results show that double line-to-ground fault is of the most importance among different types of short-circuit faults. It was revealed that when it comes to the design of the rotor magnetic shields, in addition to the eddy current distribution and the associated ohmic losses, two phase-to-ground fault should be taken into account since the produced electromagnetic forces in the time of fault conditions are more severe during double line-to-ground fault.

Exact finite elements for conduction and convection

NASA Technical Reports Server (NTRS)

Thornton, E. A.; Dechaumphai, P.; Tamma, K. K.

1981-01-01

An appproach for developing exact one dimensional conduction-convection finite elements is presented. Exact interpolation functions are derived based on solutions to the governing differential equations by employing a nodeless parameter. Exact interpolation functions are presented for combined heat transfer in several solids of different shapes, and for combined heat transfer in a flow passage. Numerical results demonstrate that exact one dimensional elements offer advantages over elements based on approximate interpolation functions. Previously announced in STAR as N81-31507

A representation of solution of stochastic differential equations

NASA Astrophysics Data System (ADS)

Kim, Yoon Tae; Jeon, Jong Woo

2006-03-01

We prove that the logarithm of the formal power series, obtained from a stochastic differential equation, is an element in the closure of the Lie algebra generated by vector fields being coefficients of equations. By using this result, we obtain a representation of the solution of stochastic differential equations in terms of Lie brackets and iterated Stratonovich integrals in the algebra of formal power series.

Global Mapping of Cell Type–Specific Open Chromatin by FAIRE-seq Reveals the Regulatory Role of the NFI Family in Adipocyte Differentiation

PubMed Central

Yu, Jing; Hirose-Yotsuya, Lisa; Take, Kazumi; Sun, Wei; Iwabu, Masato; Okada-Iwabu, Miki; Fujita, Takanori; Aoyama, Tomohisa; Tsutsumi, Shuichi; Ueki, Kohjiro; Kodama, Tatsuhiko; Sakai, Juro; Aburatani, Hiroyuki; Kadowaki, Takashi

2011-01-01

Identification of regulatory elements within the genome is crucial for understanding the mechanisms that govern cell type–specific gene expression. We generated genome-wide maps of open chromatin sites in 3T3-L1 adipocytes (on day 0 and day 8 of differentiation) and NIH-3T3 fibroblasts using formaldehyde-assisted isolation of regulatory elements coupled with high-throughput sequencing (FAIRE-seq). FAIRE peaks at the promoter were associated with active transcription and histone modifications of H3K4me3 and H3K27ac. Non-promoter FAIRE peaks were characterized by H3K4me1+/me3-, the signature of enhancers, and were largely located in distal regions. The non-promoter FAIRE peaks showed dynamic change during differentiation, while the promoter FAIRE peaks were relatively constant. Functionally, the adipocyte- and preadipocyte-specific non-promoter FAIRE peaks were, respectively, associated with genes up-regulated and down-regulated by differentiation. Genes highly up-regulated during differentiation were associated with multiple clustered adipocyte-specific FAIRE peaks. Among the adipocyte-specific FAIRE peaks, 45.3% and 11.7% overlapped binding sites for, respectively, PPARγ and C/EBPα, the master regulators of adipocyte differentiation. Computational motif analyses of the adipocyte-specific FAIRE peaks revealed enrichment of a binding motif for nuclear family I (NFI) transcription factors. Indeed, ChIP assay showed that NFI occupy the adipocyte-specific FAIRE peaks and/or the PPARγ binding sites near PPARγ, C/EBPα, and aP2 genes. Overexpression of NFIA in 3T3-L1 cells resulted in robust induction of these genes and lipid droplet formation without differentiation stimulus. Overexpression of dominant-negative NFIA or siRNA–mediated knockdown of NFIA or NFIB significantly suppressed both induction of genes and lipid accumulation during differentiation, suggesting a physiological function of these factors in the adipogenic program. Together, our study demonstrates the utility of FAIRE-seq in providing a global view of cell type–specific regulatory elements in the genome and in identifying transcriptional regulators of adipocyte differentiation. PMID:22028663

Contribution of zonal harmonics to gravitational moment

NASA Technical Reports Server (NTRS)

Roithmayr, Carlos M.

1991-01-01

It is presently demonstrated that a recursive vector-dyadic expression for the contribution of a zonal harmonic of degree n to the gravitational moment about a small body's center-of-mass is obtainable with a procedure that involves twice differentiating a celestial body's gravitational potential with respect to a vector. The recursive property proceeds from taking advantage of a recursion relation for Legendre polynomials which appear in the gravitational potential. The contribution of the zonal harmonic of degree 2 is consistent with the gravitational moment exerted by an oblate spheroid.

Contribution of zonal harmonics to gravitational moment

NASA Astrophysics Data System (ADS)

Roithmayr, Carlos M.

1991-02-01

It is presently demonstrated that a recursive vector-dyadic expression for the contribution of a zonal harmonic of degree n to the gravitational moment about a small body's center-of-mass is obtainable with a procedure that involves twice differentiating a celestial body's gravitational potential with respect to a vector. The recursive property proceeds from taking advantage of a recursion relation for Legendre polynomials which appear in the gravitational potential. The contribution of the zonal harmonic of degree 2 is consistent with the gravitational moment exerted by an oblate spheroid.

Modulation of Stem Cells Differentiation and Myostatin as an Approach to Counteract Fibrosis in Muscle Dystrophy and Regeneration After Injury

DTIC Science & Technology

2009-03-01

with and without injury; B) start effects on mdx muscle repair by Mst siRNA and stem cells programmed or not with this construct;. BODY...antifibrotic effect will be enhanced by the combinations with stem cells , or exerted by them alone, but this is the new approach that we intend to apply...similar approaches to prevent or repair muscle necrosis in the mdx mouse if the regulat MDSC or the Oct-$+ muscle cells are not effective

Human multipotent adult progenitor cells are nonimmunogenic and exert potent immunomodulatory effects on alloreactive T-cell responses.

PubMed

Jacobs, Sandra A; Pinxteren, Jef; Roobrouck, Valerie D; Luyckx, Ariane; van't Hof, Wouter; Deans, Robert; Verfaillie, Catherine M; Waer, Mark; Billiau, An D; Van Gool, Stefaan W

2013-01-01

Multipotent adult progenitor cells (MAPCs) are bone marrow-derived nonhematopoietic stem cells with a broad differentiation potential and extensive expansion capacity. A comparative study between human mesenchymal stem cells (hMSCs) and human MAPCs (hMAPCs) has shown that hMAPCs have clearly distinct phenotypical and functional characteristics from hMSCs. In particular, hMAPCs express lower levels of MHC class I than hMSCs and cannot only differentiate into typical mesenchymal cell types but can also differentiate in vitro and in vivo into functional endothelial cells. The use of hMSCs as cellular immunomodulatory stem cell products gained much interest since their immunomodulatory capacities in vitro became evident over the last decade. Currently, the clinical grade stem cell product of hMAPCs is already used in clinical trials to prevent graft-versus-host disease (GVHD), as well as for the treatment of acute myocardial infarct, ischemic stroke, and Crohn's disease. Therefore, we studied the immune phenotype, immunogenicity, and immunosuppressive effect of hMAPCs in vitro. We demonstrated that hMAPCs are nonimmunogenic for T-cell proliferation and cytokine production. In addition, hMAPCs exert strong immunosuppressive effects on T-cell alloreactivity and on T-cell proliferation induced by mitogens and recall antigens. This immunomodulatory effect was not MHC restricted, which makes off-the-shelf use promising. The immunosuppressive effect of hMAPCs is partially mediated via soluble factors and dependent on indoleamine 2,3-dioxygenase (IDO) activity. At last, we isolated hMAPCs, the clinical grade stem cell product of hMAPCs, named MultiStem, and hMSCs from one single donor and observed that both the immunogenicity and the immunosuppressive capacities of all three stem cell products are comparable in vitro. In conclusion, hMAPCs have potent immunomodulatory properties in vitro and can serve as a valuable cell source for the clinical use of immunomodulatory cellular stem cell product.

Integrated transcriptomic and proteomic analysis of the bile stress response in probiotic Lactobacillus salivarius LI01.

PubMed

Lv, Long-Xian; Yan, Ren; Shi, Hai-Yan; Shi, Ding; Fang, Dai-Qiong; Jiang, Hui-Yong; Wu, Wen-Rui; Guo, Fei-Fei; Jiang, Xia-Wei; Gu, Si-Lan; Chen, Yun-Bo; Yao, Jian; Li, Lan-Juan

2017-01-06

Lactobacillus salivarius LI01, isolated from healthy humans, has demonstrated probiotic properties in the prevention and treatment of liver failure. Tolerance to bile stress is crucial to allow lactobacilli to survive in the gastrointestinal tract and exert their benefits. In this work, we used a Digital Gene Expression transcriptomic and iTRAQ LC-MS/MS proteomic approach to examine the characteristics of LI01 in response to bile stress. Using culture medium with or without 0.15% ox bile, 591 differentially transcribed genes and 347 differentially expressed proteins were detected in LI01. Overall, we found the bile resistance of LI01 to be based on a highly remodeled cell envelope and a reinforced bile efflux system rather than on the activity of bile salt hydrolases. Additionally, some differentially expressed genes related to regulatory systems, the general stress response and central metabolism processes, also play roles in stress sensing, bile-induced damage prevention and energy efficiency. Moreover, bile salts appear to enhance proteolysis and amino acid uptake (especially aromatic amino acids) by LI01, which may support the liver protection properties of this strain. Altogether, this study establishes a model of global response mechanism to bile stress in L. salivarius LI01. L. salivarius strain LI01 exhibits not only antibacterial and antifungal properties but also exerts a good health-promoting effect in acute liver failure. As a potential probiotic strain, the bile-tolerance trait of strain LI01 is important, though this has not yet been explored. In this study, an analysis based on DGE and iTRAQ was performed to investigate the gene expression in strain LI01 under bile stress at the mRNA and protein levels, respectively. To our knowledge, this work also represents the first combined transcriptomic and proteomic analysis of the bile stress response mechanism in L. salivarius. Copyright © 2016. Published by Elsevier B.V.

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.

Local algebraic analysis of differential systems

NASA Astrophysics Data System (ADS)

Kaptsov, O. V.

2015-06-01

We propose a new approach for studying the compatibility of partial differential equations. This approach is a synthesis of the Riquier method, Gröbner basis theory, and elements of algebraic geometry. As applications, we consider systems including the wave equation and the sine-Gordon equation.

Heparin-binding EGF-like growth factor and miR-1192 exert opposite effect on Runx2-induced osteogenic differentiation.

PubMed

Yu, S; Geng, Q; Ma, J; Sun, F; Yu, Y; Pan, Q; Hong, A

2013-10-17

Osteoblast differentiation is a pivotal event in bone formation. Runt-related transcription factor-2 (Runx2) is an essential factor required for osteoblast differentiation and bone formation. However, the underlying mechanism of Runx2-regulated osteogenic differentiation is still unclear. Here, we explored the corresponding mechanism using the C2C12/Runx2(Dox) subline, which expresses Runx2 in response to doxycycline (Dox). We found that Runx2-induced osteogenic differentiation of C2C12 cells results in a sustained decrease in the expression of heparin-binding EGF-like growth factor (HB-EGF), a member of the epidermal growth factor (EGF) family. Forced expression of HB-EGF or treatment with HB-EGF is capable of reducing the expression of alkaline phosphatase (ALP), a defined marker of early osteoblast differentiation. HB-EGF-mediated inhibition of ALP depends upon activation of the EGFR and the downstream extracellular signal-regulated kinase, c-Jun N-terminal kinase mitogen-activated protein kinase pathways as well as phosphatidylinositol 3-kinase/Akt pathway. Runx2 specifically binds to the Hbegf promoter, suggesting that Hbegf transcription is directly inhibited by Runx2. Runx2 can upregulate miR-1192, which enhances Runx2-induced osteogenic differentiation. Moreover, miR-1192 directly targets Hbegf through translational inhibition, suggesting enhancement of Runx2-induced osteogenic differentiation by miR-1192 through the downregulation of HB-EGF. Taken together, our results suggest that Runx2 induces osteogenic differentiation of C2C12 cells by inactivating HB-EGF-EGFR signaling through the downregulation of HB-EGF via both transcriptional and post-transcriptional mechanisms.

Heparin-binding EGF-like growth factor and miR-1192 exert opposite effect on Runx2-induced osteogenic differentiation

PubMed Central

Yu, S; Geng, Q; Ma, J; Sun, F; Yu, Y; Pan, Q; Hong, A

2013-01-01

Osteoblast differentiation is a pivotal event in bone formation. Runt-related transcription factor-2 (Runx2) is an essential factor required for osteoblast differentiation and bone formation. However, the underlying mechanism of Runx2-regulated osteogenic differentiation is still unclear. Here, we explored the corresponding mechanism using the C2C12/Runx2Dox subline, which expresses Runx2 in response to doxycycline (Dox). We found that Runx2-induced osteogenic differentiation of C2C12 cells results in a sustained decrease in the expression of heparin-binding EGF-like growth factor (HB-EGF), a member of the epidermal growth factor (EGF) family. Forced expression of HB-EGF or treatment with HB-EGF is capable of reducing the expression of alkaline phosphatase (ALP), a defined marker of early osteoblast differentiation. HB-EGF-mediated inhibition of ALP depends upon activation of the EGFR and the downstream extracellular signal-regulated kinase, c-Jun N-terminal kinase mitogen-activated protein kinase pathways as well as phosphatidylinositol 3-kinase/Akt pathway. Runx2 specifically binds to the Hbegf promoter, suggesting that Hbegf transcription is directly inhibited by Runx2. Runx2 can upregulate miR-1192, which enhances Runx2-induced osteogenic differentiation. Moreover, miR-1192 directly targets Hbegf through translational inhibition, suggesting enhancement of Runx2-induced osteogenic differentiation by miR-1192 through the downregulation of HB-EGF. Taken together, our results suggest that Runx2 induces osteogenic differentiation of C2C12 cells by inactivating HB-EGF-EGFR signaling through the downregulation of HB-EGF via both transcriptional and post-transcriptional mechanisms. PMID:24136232

Parallel Element Agglomeration Algebraic Multigrid and Upscaling Library

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

Barker, Andrew T.; Benson, Thomas R.; Lee, Chak Shing

ParELAG is a parallel C++ library for numerical upscaling of finite element discretizations and element-based algebraic multigrid solvers. It provides optimal complexity algorithms to build multilevel hierarchies and solvers that can be used for solving a wide class of partial differential equations (elliptic, hyperbolic, saddle point problems) on general unstructured meshes. Additionally, a novel multilevel solver for saddle point problems with divergence constraint is implemented.

Bernard J. Wood Receives 2013 Harry H. Hess Medal: Citation

NASA Astrophysics Data System (ADS)

Hofmann, Albrecht W.

2014-01-01

As Harry Hess recognized over 50 years ago, mantle melting is the fundamental motor for planetary evolution and differentiation. Melting generates the major divisions of crust mantle and core. The distribution of chemical elements between solids, melts, and gaseous phases is fundamental to understanding these differentiation processes. Bernie Wood, together with Jon Blundy, has combined experimental petrology and physicochemical theory to revolutionize the understanding of the distribution of trace elements between melts and solids in the Earth. Knowledge of these distribution laws allows the reconstruction of the source compositions of the melts (deep in Earth's interior) from their abundances in volcanic rocks. Bernie's theoretical treatment relates the elastic strain of the lattice caused by the substitution of a trace element in a crystal to the ionic radius and charge of this element. This theory, and its experimental calibrations, brought order to a literature of badly scattered, rather chaotic experimental data that allowed no satisfactory quantitative modeling of melting processes in the mantle.

Experimental characterization of novel microdiffuser elements

NASA Astrophysics Data System (ADS)

Ehrlich, L.; Punch, J.; Jeffers, N.; Stafford, J.

2014-07-01

Micropumps can play a significant role in thermal management applications, as a component of microfluidic cooling systems. For next-generation high density optical communication systems, in particular, heat flux levels are sufficiently high to require a microfluidic circuit for cooling. Valveless piezoelectrically-actuated micropumps are a particularly promising technology to be deployed for this application. These pumps exploit the asymmetric flow behaviour of microdiffusers to achieve net flow. They feature no rotating or contacting parts, which make them intrinsically reliable in comparison to micropumps with active valves. In this paper, two novel microdiffuser elements are reported and characterized. The micropumps were fabricated using a 3D Printer. Each single diffuser had a length of 1800 pm and a depth of 400 pm. An experimental characterization was conducted in which the flow rate and differential pressure were measured as a function of operating frequency. In comparison with standard diffuser, both elements showed an increase in differential pressure in the range of 40 - 280 %, but only one of the elements exhibited an improved flow rate, of about 85 %.

Quasi-Static Viscoelastic Finite Element Model of an Aircraft Tire

NASA Technical Reports Server (NTRS)

Johnson, Arthur R.; Tanner, John A.; Mason, Angela J.

1999-01-01

An elastic large displacement thick-shell mixed finite element is modified to allow for the calculation of viscoelastic stresses. Internal strain variables are introduced at the element's stress nodes and are employed to construct a viscous material model. First order ordinary differential equations relate the internal strain variables to the corresponding elastic strains at the stress nodes. The viscous stresses are computed from the internal strain variables using viscous moduli which are a fraction of the elastic moduli. The energy dissipated by the action of the viscous stresses is included in the mixed variational functional. The nonlinear quasi-static viscous equilibrium equations are then obtained. Previously developed Taylor expansions of the nonlinear elastic equilibrium equations are modified to include the viscous terms. A predictor-corrector time marching solution algorithm is employed to solve the algebraic-differential equations. The viscous shell element is employed to computationally simulate a stair-step loading and unloading of an aircraft tire in contact with a frictionless surface.

Toxic trace elements at gastrointestinal level.

PubMed

Vázquez, M; Calatayud, M; Jadán Piedra, C; Chiocchetti, G M; Vélez, D; Devesa, V

2015-12-01

Many trace elements are considered essential [iron (Fe), zinc (Zn), copper (Cu)], whereas others may be harmful [lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As)], depending on their concentration and chemical form. In most cases, the diet is the main pathway by which they enter our organism. The presence of toxic trace elements in food has been known for a long time, and many of the food matrices that carry them have been identified. This has led to the appearance of legislation and recommendations concerning consumption. Given that the main route of exposure is oral, passage through the gastrointestinal tract plays a fundamental role in their entry into the organism, where they exert their toxic effect. Although the digestive system can be considered to be of crucial importance in their toxicity, in most cases we do not know the events that occur during the passage of these elements through the gastrointestinal tract and of ascertaining whether they may have some kind of toxic effect on it. The aim of this review is to summarize available information on this subject, concentrating on the toxic trace elements that are of greatest interest for organizations concerned with food safety and health: Pb, Cd, Hg and As. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Content of the 14 Metals in Cancellous and Cortical Bone of the Hip Joint Affected by Osteoarthritis

PubMed Central

Zioła-Frankowska, Anetta; Kubaszewski, Łukasz; Dąbrowski, Mikołaj; Kowalski, Artur; Rogala, Piotr; Strzyżewski, Wojciech; Łabędź, Wojciech; Kanicky, Viktor

2015-01-01

The aim of the study was to determine the content of particular elements Ca, Mg, P, Na, K, Zn, Cu, Fe, Mo, Cr, Ni, Ba, Sr, and Pb in the proximal femur bone tissue (cancellous and cortical bone) of 96 patients undergoing total hip replacement for osteoarthritis using ICP-AES and FAAS analytical techniques. The interdependencies among these elements and their correlations depended on factors including age, gender, place of residence, tobacco consumption, alcohol consumption, exposure to environmental pollution, physical activity, and type of degenerative change which were examined by statistical and chemometric methods. The factors that exerted the greatest influence on the elements in the femoral head and neck were tobacco smoking (higher Cr and Ni content in smokers), alcohol consumption (higher concentrations of Ni, Cu in people who consume alcohol), and gender (higher Cu, Zn, and Ni concentrations in men). The factors influencing Pb accumulation in bone tissue were tobacco, alcohol, gender, and age. In primary and secondary osteoarthritis of the hip, the content and interactions of elements are different (mainly those of Fe and Pb). There were no significant differences in the concentrations of elements in the femoral head and neck that could be attributed to residence or physical activity. PMID:26357659

IAA8 expression during vascular cell differentiation

Treesearch

Andrew T. Groover; Amy Pattishall; Alan M. Jones

2003-01-01

We report the characterization of a member of the auxin-induced IAA gene family from zinnia, designated zIAA8, which is expressed by mesophyll cells differentiating as tracheary elements in vitro. Transcription of zIAA8 is upregulated within 3 h after cell isolation in inductive medium,...

Cost Differential Analysis: Providing Data for Added Cost Funding

ERIC Educational Resources Information Center

Nystrom, Dennis C.; Hennessy, James V.

1975-01-01

A 1972-73 statewide study conducted in Illinois to develop a cost accounting system which facilitates cost differential ratios for secondary vocational education courses indicated that vocational programs are approximately twice as expensive as nonvocational. Specific cost elements identified in the study provided essential information regarding…

Differentiation in Data Analysis & Probability, PreK-Grade 2: A Content Companion for Ongoing Assessment, Grouping Students, Targeting Instruction, and Adjusting Levels of Cognitive Demand

ERIC Educational Resources Information Center

Taylor-Cox, Jennifer

2008-01-01

This book applies the author's easy but effective differentiation strategies to the data analysis and probability content standard. Taking the foundational elements of differentiation in this book, it helps you: (1) assess students' math abilities quickly and efficiently; (2) group children by need; (3) target instruction to meet every student's…

Space-Pseudo-Time Method: Application to the One-Dimensional Coulomb Potential and Density Funtional Theory

NASA Astrophysics Data System (ADS)

Weatherford, Charles; Gebremedhin, Daniel

2016-03-01

A new and efficient way of evolving a solution to an ordinary differential equation is presented. A finite element method is used where we expand in a convenient local basis set of functions that enforce both function and first derivative continuity across the boundaries of each element. We also implement an adaptive step size choice for each element that is based on a Taylor series expansion. The method is applied to solve for the eigenpairs of the one-dimensional soft-coulomb potential and the hard-coulomb limit is studied. The method is then used to calculate a numerical solution of the Kohn-Sham differential equation within the local density approximation is presented and is applied to the helium atom. Supported by the National Nuclear Security Agency, the Nuclear Regulatory Commission, and the Defense Threat Reduction Agency.

A Geochemical Study of Postshield Volcanism and the Generation of Trachyte on West Maui, HI

NASA Astrophysics Data System (ADS)

Trenkler, M. L.; Cousens, B.

2016-12-01

The West Maui Volcano provides a complete evolutionary history of a fully developed Hawaiian volcano described by three main phases: (1) the tholeiitic shield-building stage of the Wailuku Basalts; (2) the postshield alkalic stage Honolua Volcanics; and (3) the rejuvenated stage Lahaina Volcanics of silica-undersaturated rocks. On West Maui, the postshield Honolua Volcanics erupted highly differentiated rocks (benmoreite to trachyte), with little to no intermediate alkalic rocks, upon cessation of tholeiitic shield building. Utilizing K-Ar dated samples, we present 35 new major and trace element analyses of shield, postshield, and rejuvenated stage lavas on West Maui in an attempt to identify the mechanisms present during evolution from basalt to trachyte over a defined temporal and spatial range. Wailuku basalts are dominated by olivine fractionation, whereas decreasing Sc and CaO/Al2O3 with increasing degree of differentiation indicate Honolua benmoreites and trachytes heavily fractionated clinopyroxene. Major element trends are consistent with crystallization of titano-magnetite, potassium feldspar, and minor apatite. Trace element patterns of the Honolua Volcanics are uniform with strong enrichments in LILE and the LREEs indicating fractionation and lower degrees of partial melting compared to Wailuku basalts. The HREEs are enriched relative to shield basalts with Gd/Yb values of 2.0-2.8 as a result of high degrees of fractionation and the presence of crystalizing apatite. Major and trace element trends follow the evolution of the postshield Hawi Volcanics of Kohala, where alkalic basalts differentiate up to trachyte. Compared to shield lavas, the Honolua Volcanics represent a drastic decrease in magma supply rates, infrequent eruptions, and magma residence times long enough to produce highly differentiated magmas with no significant mafic magma input.

A Differential Chemical Element Analysis of the Metal-poor Globular Cluster NGC 6397

NASA Astrophysics Data System (ADS)

Koch, Andreas; McWilliam, Andrew

2011-08-01

We present chemical abundances in three red giants and two turnoff (TO) stars in the metal-poor Galactic globular cluster (GC) NGC 6397 based on spectroscopy obtained with the Magellan Inamori Kyocera Echelle high-resolution spectrograph on the Magellan 6.5 m Clay telescope. Our results are based on a line-by-line differential abundance analysis relative to the well-studied red giant Arcturus and the Galactic halo field star Hip 66815. At a mean of -2.10 ± 0.02 (stat.) ±0.07 (sys.), the differential iron abundance is in good agreement with other studies in the literature based on gf-values. As in previous differential works we find a distinct departure from ionization equilibrium in that the abundances of Fe I and Fe II differ by ~0.1 dex, with opposite signs for the red giant branch (RGB) and TO stars. The α-element ratios are enhanced to 0.4 (RGB) and 0.3 dex (TO), respectively, and we also confirm strong variations in the O, Na, and Al/Fe abundance ratios. Accordingly, the light-element abundance patterns in one of the red giants can be attributed to pollution by an early generation of massive Type II supernovae. TO and RGB abundances are not significantly different, with the possible exception of Mg and Ti, which are, however, amplified by the patterns in one TO star additionally belonging to this early generation of GC stars. We discuss interrelations of these light elements as a function of the GC metallicity. This paper includes data gathered with the 6.5 m Magellan Telescopes located at Las Campanas Observatory, Chile.

Cholesterol negatively regulates IL-9-producing CD8+ T cell differentiation and antitumor activity.

PubMed

Ma, Xingzhe; Bi, Enguang; Huang, Chunjian; Lu, Yong; Xue, Gang; Guo, Xing; Wang, Aibo; Yang, Maojie; Qian, Jianfei; Dong, Chen; Yi, Qing

2018-05-09

CD8 + T cells can be polarized into IL-9-secreting (Tc9) cells. We previously showed that adoptive therapy using tumor-specific Tc9 cells generated stronger antitumor responses in mouse melanoma than classical Tc1 cells. To understand why Tc9 cells exert stronger antitumor responses, we used gene profiling to compare Tc9 and Tc1 cells. Tc9 cells expressed different levels of cholesterol synthesis and efflux genes and possessed significantly lower cholesterol content than Tc1 cells. Unique to Tc9, but not other CD8 + or CD4 + T cell subsets, manipulating cholesterol content in polarizing Tc9 cells significantly affected IL-9 expression and Tc9 differentiation and antitumor response in vivo. Mechanistic studies showed that IL-9 was indispensable for Tc9 cell persistence and antitumor effects, and cholesterol or its derivatives inhibited IL-9 expression by activating liver X receptors (LXRs), leading to LXR Sumoylation and reduced p65 binding to Il9 promoter. Our study identifies cholesterol as a critical regulator of Tc9 cell differentiation and function. © 2018 Ma et al.

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.

Herbivory at marginal populations: Consequences for maternal fitness and vegetative differentiation

NASA Astrophysics Data System (ADS)

Castilla, Antonio R.; Alonso, Conchita; Herrera, Carlos M.

2013-05-01

Margins of distribution of plant species constitute natural areas where the impact of the antagonistic interactions is expected to be higher and where changes in the dynamics of plant-herbivore coevolution could promote intraspecific differentiation in (co)evolving plant traits. In the present study, we investigated how differences in the average herbivory level affect maternal fitness in core continuous and marginal disjunct populations of Daphne laureola in an effort to assess the role of herbivores limiting plant distribution. Furthermore, we investigated intraspecific differentiation in vegetative traits and their potential connection to divergent selection by herbivores in both groups of populations. Our results did not support increased herbivory at the species margin but did support a difference in the effect of herbivory on maternal fitness between core continuous and marginal disjunct populations of D. laureola. In addition, herbivores did not exert phenotypic selection consistent with the geographic variation in studied plant traits. Therefore, the geographic variation of vegetative traits of D. laureola seems to be consequence of environmental heterogeneity more than result of geographically divergent selection by herbivores.

Role of substrate biomechanics in controlling (stem) cell fate: Implications in regenerative medicine.

PubMed

Macri-Pellizzeri, Laura; De-Juan-Pardo, Elena M; Prosper, Felipe; Pelacho, Beatriz

2018-04-01

Tissue-specific stem cells reside in a specialized environment known as niche. The niche plays a central role in the regulation of cell behaviour and, through the concerted action of soluble molecules, supportive somatic cells, and extracellular matrix components, directs stem cells to proliferate, differentiate, or remain quiescent. Great efforts have been done to decompose and separately analyse the contribution of these cues in the in vivo environment. Specifically, the mechanical properties of the extracellular matrix influence many aspects of cell behaviour, including self-renewal and differentiation. Deciphering the role of biomechanics could thereby provide important insights to control the stem cells responses in a more effective way with the aim to promote their therapeutic potential. In this review, we provide a wide overview of the effect that the microenvironment stiffness exerts on the control of cell behaviour with a particular focus on the induction of stem cells differentiation. We also describe the process of mechanotransduction and the molecular effectors involved. Finally, we critically discuss the potential involvement of tissue biomechanics in the design of novel tissue engineering strategies. Copyright © 2017 John Wiley & Sons, Ltd.

Chitosan stabilizes platelet growth factors and modulates stem cell differentiation toward tissue regeneration.

PubMed

Busilacchi, Alberto; Gigante, Antonio; Mattioli-Belmonte, Monica; Manzotti, Sandra; Muzzarelli, Riccardo A A

2013-10-15

The idea of using chitosan as a functional delivery aid to support simultaneously PRP, stem cells and growth factors (GF) is associated with the intention to use morphogenic biomaterials to modulate the natural healing sequence in bone and other tissues. For example, chitosan-chondroitin sulfate loaded with platelet lysate was included in a poly(D,L-lactate) foam that was then seeded with human adipose-derived stem cells and cultured in vitro under osteogenic stimulus: the platelet lysate provided to the bone tissue the most suitable assortment of GF which induces the osteogenic differentiation of the mesenchymal stem cells. PDGF, FGF, IGF and TGF-β were protagonists in the repair of callus fractures. The release of GF from the composites of chitosan-PRP and either nano-hydroxyapatite or tricalcium phosphate was highly beneficial for enhancing MSC proliferation and differentiation, thus qualifying chitosan as an excellent vehicle. A number of biochemical characteristics of chitosan exert synergism with stem cells in the regeneration of soft tissues. Copyright © 2013 Elsevier Ltd. 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

Adhesion, Vitality and Osteogenic Differentiation Capacity of Adipose Derived Stem Cells Seeded on Nitinol Nanoparticle Coatings

PubMed Central

Strauß, Sarah; Neumeister, Anne; Barcikowski, Stephan; Kracht, Dietmar; Kuhbier, Jörn W.; Radtke, Christine; Reimers, Kerstin; Vogt, Peter M.

2013-01-01

Autologous cells can be used for a bioactivation of osteoimplants to enhance osseointegration. In this regard, adipose derived stem cells (ASCs) offer interesting perspectives in implantology because they are fast and easy to isolate. However, not all materials licensed for bone implants are equally suited for cell adhesion. Surface modifications are under investigation to promote cytocompatibility and cell growth. The presented study focused on influences of a Nitinol-nanoparticle coating on ASCs. Possible toxic effects as well as influences on the osteogenic differentiation potential of ASCs were evaluated by viability assays, scanning electron microscopy, immunofluorescence and alizarin red staining. It was previously shown that Nitinol-nanoparticles exert no cell toxic effects to ASCs either in soluble form or as surface coating. Here we could demonstrate that a Nitinol-nanoparticle surface coating enhances cell adherence and growth on Nitinol-surfaces. No negative influence on the osteogenic differentiation was observed. Nitinol-nanoparticle coatings offer new possibilities in implantology research regarding bioactivation by autologous ASCs, respectively enhancement of surface attraction to cells. PMID:23308190

DNA-damage-induced differentiation of leukaemic cells as an anti-cancer barrier

PubMed Central

Santos, Margarida A.; Faryabi, Robert B.; Ergen, Aysegul V.; Day, Amanda M.; Malhowski, Amy; Canela, Andres; Onozawa, Masahiro; Lee, Ji-Eun; Callen, Elsa; Gutierrez-Martinez, Paula; Chen, Hua-Tang; Wong, Nancy; Finkel, Nadia; Deshpande, Aniruddha; Sharrow, Susan; Rossi, Derrick J.; Ito, Keisuke; Ge, Kai; Aplan, Peter D.; Armstrong, Scott A.; Nussenzweig, André

2015-01-01

Self-renewal is the hallmark feature both of normal stem cells and cancer stem cells1. Since the regenerative capacity of normal haematopoietic stem cells is limited by the accumulation of reactive oxygen species and DNA double-strand breaks2–4, we speculated that DNA damage might also constrain leukaemic self-renewal and malignant haematopoiesis. Here we show that the histone methyl-transferase MLL4, a suppressor of B-cell lymphoma5,6, is required for stem-cell activity and an aggressive form of acute myeloid leukaemia harbouring the MLL–AF9 oncogene. Deletion of MLL4 enhances myelopoiesis and myeloid differentiation of leukaemic blasts, which protects mice from death related to acute myeloid leukaemia. MLL4 exerts its function by regulating transcriptional programs associated with the antioxidant response. Addition of reactive oxygen species scavengers or ectopic expression of FOXO3 protects MLL4−/− MLL–AF9 cells from DNA damage and inhibits myeloid maturation. Similar to MLL4 deficiency, loss of ATM or BRCA1 sensitizes transformed cells to differentiation, suggesting that myeloid differentiation is promoted by loss of genome integrity. Indeed, we show that restriction-enzyme-induced double-strand breaks are sufficient to induce differentiation of MLL–AF9 blasts, which requires cyclin-dependent kinase inhibitor p21Cip1 (Cdkn1a) activity. In summary, we have uncovered an unexpected tumour-promoting role of genome guardians in enforcing the oncogene-induced differentiation blockade in acute myeloid leukaemia. PMID:25079327

Murine bone cell lines as models for spaceflight induced effects on differentiation and gene expression

NASA Astrophysics Data System (ADS)

Lau, P.; Hellweg, C. E.; Baumstark-Khan, C.; Reitz, G.

Critical health factors for space crews especially on long-term missions are radiation exposure and the absence of gravity DNA double strand breaks DSB are presumed to be the most deleterious DNA lesions after radiation as they disrupt both DNA strands in close proximity Besides radiation risk the absence of gravity influences the complex skeletal apparatus concerning muscle and especially bone remodelling which results from mechanical forces exerting on the body Bone is a dynamic tissue which is life-long remodelled by cells from the osteoblast and osteoclast lineage Any imbalance of this system leads to pathological conditions such as osteoporosis or osteopetrosis Osteoblastic cells play a crucial role in bone matrix synthesis and differentiate either into bone-lining cells or into osteocytes Premature terminal differentiation has been reported to be induced by a number of DNA damaging or cell stress inducing agents including ionising and ultraviolet radiation as well as treatment with mitomycin C In the present study we compare the effects of sequential differentiation by adding osteoinductive substances ss -glycerophosphate and ascorbic acid Radiation-induced premature differentiation was investigated regarding the biosynthesis of specific osteogenic marker molecules and the differentiation dependent expression of marker genes The bone cell model established in our laboratory consists of the osteocyte cell line MLO-Y4 the osteoblast cell line OCT-1 and the subclones 4 and 24 of the osteoblast cell line MC3T3-E1 expressing several

Probing chromatin structure with nuclease sensitivity assays.

PubMed

Gregory, R I; Khosla, S; Feil, R

2001-01-01

To further our understanding of genomic imprinting it will be essential to identify key control elements, and to investigate their regulation by both epigenetic modifications (such as DNA methylation) and trans-acting factors. So far, sequence elements that regulate parental allele-specific gene expression have been identified in a number of imprinted loci, either because of their differential DNA methylation or through functional studies in transgenic mice (1,2). A systematic search for allele-specific chromatin features constitutes an alternative strategy to identify elements that regulate imprinting. The validity of such an in vivo chromatin approach derives from the fact that in several known imprinting control-elements, a specialized organization of chromatin characterized by nuclease hypersensitivity is present on only one of the two parental chromosome (3). For example, the differentially methylated 5 -portion of the human SNRPN gene-a sequence element that controls imprinting in the Prader-Willi and Angelman syndromes' domain on chromosome 15q11- q13-has strong DNase-I hypersensitive sites on the unmethylated paternal chromosome (4). A differentially methylated region that regulates the imprinting of H19 and that of the neighboring insulin-like growth factor-2 gene on mouse chromosome 7 was also found to have parental chromosome-specific hypersensitive sites (5,6). The precise nature of the allelic nuclease hypersensitivity in these and other imprinted loci remains to be determined in more detail, for example, by applying complementary chromatin methodologies (7,8). However, it is commonly observed that a nuclease hypersensitive site corresponds to a small region where nucleosomes are absent or partially disrupted.

Dynamically stable magnetic suspension/bearing system

DOEpatents

Post, R.F.

1996-02-27

A magnetic bearing system contains magnetic subsystems which act together to support a rotating element in a state of dynamic equilibrium. However, owing to the limitations imposed by Earnshaw`s Theorem, the magnetic bearing systems to be described do not possess a stable equilibrium at zero rotational speed. Therefore, mechanical stabilizers are provided, in each case, to hold the suspended system in equilibrium until its speed has exceeded a low critical speed where dynamic effects take over, permitting the achievement of a stable equilibrium for the rotating object. A state of stable equilibrium is achieved above a critical speed by use of a collection of passive elements using permanent magnets to provide their magnetomotive excitation. The magnetic forces exerted by these elements, when taken together, levitate the rotating object in equilibrium against external forces, such as the force of gravity or forces arising from accelerations. At the same time, this equilibrium is made stable against displacements of the rotating object from its equilibrium position by using combinations of elements that possess force derivatives of such magnitudes and signs that they can satisfy the conditions required for a rotating body to be stably supported by a magnetic bearing system over a finite range of those displacements. 32 figs.

Dynamically stable magnetic suspension/bearing system

DOEpatents

Post, Richard F.

1996-01-01

A magnetic bearing system contains magnetic subsystems which act together to support a rotating element in a state of dynamic equilibrium. However, owing to the limitations imposed by Earnshaw's Theorem, the magnetic bearing systems to be described do not possess a stable equilibrium at zero rotational speed. Therefore, mechanical stabilizers are provided, in each case, to hold the suspended system in equilibrium until its speed has exceeded a low critical speed where dynamic effects take over, permitting the achievement of a stable equilibrium for the rotating object. A state of stable equilibrium is achieved above a critical speed by use of a collection of passive elements using permanent magnets to provide their magnetomotive excitation. The magnetic forces exerted by these elements, when taken together, levitate the rotating object in equilibrium against external forces, such as the force of gravity or forces arising from accelerations. At the same time, this equilibrium is made stable against displacements of the rotating object from its equilibrium position by using combinations of elements that possess force derivatives of such magnitudes and signs that they can satisfy the conditions required for a rotating body to be stably supported by a magnetic bearing system over a finite range of those displacements.

Investigation of the influence of vertical force on the contact between truck tyre and road using finite element analyses

NASA Astrophysics Data System (ADS)

Moisescu, Alexandra-Raluca; Anghelache, Gabriel

2017-10-01

In the modern context of automobile integration with the emerging technologies of the interconnected society, the interaction between tyre and road is an element of major importance for automobile safety systems such as the intelligent tyres, as well as for passenger comfort, fuel economy, environmental protection, infrastructure and vehicle durability. The tyre-road contact generates the distribution of forces exerted on each unit area in the contact patch, therefore the distribution of contact stresses on three orthogonal directions. The numerical investigation of stresses distribution in the contact patch requires the development of finite element models capable of accurately describing the interaction between tyre and rolling surface. The complex finite element model developed for the 11R22.5 truck tyre has been used for investigating the influence of vertical force on the distributions of contact stresses. In addition to these contributions, the paper presents aspects related to the simulation of truck tyre radial stiffness. The influence of tyre rolling has not been taken into consideration, as the purpose of the current research is the investigation of tyre-road contact in stationary conditions.

Elemental selenium at nano size possesses lower toxicity without compromising the fundamental effect on selenoenzymes: comparison with selenomethionine in mice.

PubMed

Wang, Huali; Zhang, Jinsong; Yu, Hanqing

2007-05-15

Glutathione peroxidase and thioredoxin reductase are major selenoenzymes through which selenium exerts powerful antioxidant effects. Selenium also elicits pro-oxidant effects at toxic levels. The antioxidant and pro-oxidant effects, or bioavailability and toxicity, of selenium depend on its chemical form. Selenomethionine is considered to be the most appropriate supplemental form due to its excellent bioavailability and lower toxicity compared to various selenium compounds. The present studies reveal that, compared with selenomethionine, elemental selenium at nano size (Nano-Se) possesses equal efficacy in increasing the activities of glutathione peroxidase and thioredoxin reductase but has much lower toxicity as indicated by median lethal dose, acute liver injury, and short-term toxicity. Our results suggest that Nano-Se can serve as an antioxidant with reduced risk of selenium toxicity.

Rubbery computing

NASA Astrophysics Data System (ADS)

Wilson, Katherine E.; Henke, E.-F. Markus; Slipher, Geoffrey A.; Anderson, Iain A.

2017-04-01

Electromechanically coupled dielectric elastomer actuators (DEAs) and dielectric elastomer switches (DESs) may form digital logic circuitry made entirely of soft and flexible materials. The expansion in planar area of a DEA exerts force across a DES, which is a soft electrode with strain-dependent resistivity. When compressed, the DES drops steeply in resistance and changes state from non-conducting to conducting. Logic operators may be achieved with different arrangements of interacting DE actuators and switches. We demonstrate combinatorial logic elements, including the fundamental Boolean logic gates, as well as sequential logic elements, including latches and flip-flops. With both data storage and signal processing abilities, the necessary calculating components of a soft computer are available. A noteworthy advantage of a soft computer with mechanosensitive DESs is the potential for responding to environmental strains while locally processing information and generating a reaction, like a muscle reflex.

Transforming Growth Factor β1/Smad4 Signaling Affects Osteoclast Differentiation via Regulation of miR-155 Expression.

PubMed

Zhao, Hongying; Zhang, Jun; Shao, Haiyu; Liu, Jianwen; Jin, Mengran; Chen, Jinping; Huang, Yazeng

2017-03-01

Transforming growth factor β1 (TGFβ1)/Smad4 signaling plays a pivotal role in maintenance of the dynamic balance between bone formation and resorption. The microRNA miR-155 has been reported to exert a significant role in the differentiation of macrophage and dendritic cells. The goal of this study was to determine whether miR-155 regulates osteoclast differentiation through TGFβ1/Smad4 signaling. Here, we present that TGFβ1 elevated miR-155 levels during osteoclast differentiation through the stimulation of M-CSF and RANKL. Additionally, we found that silencing Smad4 attenuated the upregulation of miR-155 induced by TGFβ1. The results of luciferase reporter experiments and ChIP assays demonstrated that TGFβ1 promoted the binding of Smad4 to the miR-155 promoter at a site located in 454 bp from the transcription start site in vivo , further verifying that miR-155 is a transcriptional target of the TGFβ1/Smad4 pathway. Subsequently, TRAP staining and qRT-PCR analysis revealed that silencing Smad4 impaired the TGFβ1-mediated inhibition on osteoclast differentiation. Finally, we found that miR-155 may target SOCS1 and MITF to suppress osteoclast differentiation. Taken together, we provide the first evidence that TGFβ1/Smad4 signaling affects osteoclast differentiation by regulation of miR-155 expression and the use of miR-155 as a potential therapeutic target for osteoclast-related diseases shows great promise.

Transforming Growth Factor β1/Smad4 Signaling Affects Osteoclast Differentiation via Regulation of miR-155 Expression

PubMed Central

Zhao, Hongying; Zhang, Jun; Shao, Haiyu; Liu, Jianwen; Jin, Mengran; Chen, Jinping; Huang, Yazeng

2017-01-01

Transforming growth factor β1 (TGFβ1)/Smad4 signaling plays a pivotal role in maintenance of the dynamic balance between bone formation and resorption. The microRNA miR-155 has been reported to exert a significant role in the differentiation of macrophage and dendritic cells. The goal of this study was to determine whether miR-155 regulates osteoclast differentiation through TGFβ1/Smad4 signaling. Here, we present that TGFβ1 elevated miR-155 levels during osteoclast differentiation through the stimulation of M-CSF and RANKL. Additionally, we found that silencing Smad4 attenuated the upregulation of miR-155 induced by TGFβ1. The results of luciferase reporter experiments and ChIP assays demonstrated that TGFβ1 promoted the binding of Smad4 to the miR-155 promoter at a site located in 454 bp from the transcription start site in vivo, further verifying that miR-155 is a transcriptional target of the TGFβ1/Smad4 pathway. Subsequently, TRAP staining and qRT-PCR analysis revealed that silencing Smad4 impaired the TGFβ1-mediated inhibition on osteoclast differentiation. Finally, we found that miR-155 may target SOCS1 and MITF to suppress osteoclast differentiation. Taken together, we provide the first evidence that TGFβ1/Smad4 signaling affects osteoclast differentiation by regulation of miR-155 expression and the use of miR-155 as a potential therapeutic target for osteoclast-related diseases shows great promise. PMID:28359146

Antineoplastic Effects of PPARγ Agonists, with a Special Focus on Thyroid Cancer.

PubMed

Ferrari, Silvia Martina; Materazzi, Gabriele; Baldini, Enke; Ulisse, Salvatore; Miccoli, Paolo; Antonelli, Alessandro; Fallahi, Poupak

2016-01-01

Peroxisome Proliferator-Activated Receptor-γ (PPARγ) is a ligand-activated nuclear hormone receptor that functions as transcription factor and plays an important role in lipid metabolism and insulin sensitization. Recent studies have shown that PPARγ is overexpressed in many tumor types, including cancers of breast, lung, pancreas, colon, glioblastoma, prostate and thyroid differentiated/anaplastic cancers. These data suggest a role of PPARγ in tumor development and/or progression. PPARγ is emerging as a growth-limiting and differentiation-promoting factor, and it exerts a tumor suppressor role. Moreover, naturally-occurring and synthetic PPARγ agonists promote growth inhibition and apoptosis. Thiazolidinediones (TZDs) are synthetic agonists of PPARγ that were developed to treat type II diabetes. These compounds also display anticancer effects which appear mainly to be independent of their PPARγ agonist activity. Various preclinical and clinical studies strongly suggest a role for TZDs both alone and in combination with existing chemotherapeutic agents, for the treatment of cancer. Differentiation therapy involves the use of agents with the ability to induce differentiation in cells that have lost this ability, i.e. cancer cells, targeting pathways capable of re-activating blocked terminal differentiation programs. PPARγ agonists have been shown to induce differentiation in solid tumors such as thyroid differentiated/ anaplastic cancers and sarcomas. However, emerging data suggest that chronic use of TZDs is associated with increased risk of adverse cardiovascular events. The exploration of newer PPARγ agonists can help in unveiling the underlying mechanisms of these drugs, providing new molecules that are able to treat cancer, without increasing the cardiovascular risk of neoplastic patients.

Using Mixed Methods to Interpret Differential Item Functioning

ERIC Educational Resources Information Center

Benítez, Isabel; Padilla, José-Luis; Hidalgo Montesinos, María Dolores; Sireci, Stephen G.

2016-01-01

Analysis of differential item functioning (DIF) is often used to determine if cross-lingual assessments are equivalent across languages. However, evidence on the causes of cross-lingual DIF is still evasive. Expert appraisal is a qualitative method useful for obtaining detailed information about problematic elements in the different linguistic…

Modelling the evolution and diversity of cumulative culture

PubMed Central

Enquist, Magnus; Ghirlanda, Stefano; Eriksson, Kimmo

2011-01-01

Previous work on mathematical models of cultural evolution has mainly focused on the diffusion of simple cultural elements. However, a characteristic feature of human cultural evolution is the seemingly limitless appearance of new and increasingly complex cultural elements. Here, we develop a general modelling framework to study such cumulative processes, in which we assume that the appearance and disappearance of cultural elements are stochastic events that depend on the current state of culture. Five scenarios are explored: evolution of independent cultural elements, stepwise modification of elements, differentiation or combination of elements and systems of cultural elements. As one application of our framework, we study the evolution of cultural diversity (in time as well as between groups). PMID:21199845

Lipocalin-2 inhibits osteoclast formation by suppressing the proliferation and differentiation of osteoclast lineage cells

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

Kim, Hyun-Ju, E-mail: biohjk@knu.ac.kr; Yoon, Hye-Jin; Yoon, Kyung-Ae

Lipocalin-2 (LCN2) is a member of the lipocalin superfamily and plays a critical role in the regulation of various physiological processes, such as inflammation and obesity. In this study, we report that LCN2 negatively modulates the proliferation and differentiation of osteoclast precursors, resulting in impaired osteoclast formation. The overexpression of LCN2 in bone marrow-derived macrophages or the addition of recombinant LCN2 protein inhibits the formation of multinuclear osteoclasts. LCN2 suppresses macrophage colony-stimulating factor (M-CSF)-induced proliferation of osteoclast precursor cells without affecting their apoptotic cell death. Interestingly, LCN2 decreases the expression of the M-CSF receptor, c-Fms, and subsequently blocks its downstreammore » signaling cascades. In addition, LCN2 inhibits RANKL-induced osteoclast differentiation and attenuates the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1), which are important modulators in osteoclastogenesis. Mechanistically, LCN2 inhibits NF-κB signaling pathways, as demonstrated by the suppression of IκBα phosphorylation, nuclear translocation of p65, and NF-κB transcriptional activity. Thus, LCN2 is an anti-osteoclastogenic molecule that exerts its effects by retarding the proliferation and differentiation of osteoclast lineage cells. - Highlights: • LCN2 expression is regulated during osteoclast development. • LCN2 suppresses M-CSF-mediated osteoclast precursor proliferation. • LCN2 inhibits RANKL-induced osteoclast differentiation.« less

Eicosapentaenoic acid and arachidonic acid differentially regulate adipogenesis, acquisition of a brite phenotype and mitochondrial function in primary human adipocytes.

PubMed

Fleckenstein-Elsen, Manuela; Dinnies, Daniela; Jelenik, Tomas; Roden, Michael; Romacho, Tania; Eckel, Jürgen

2016-09-01

n-3 and n-6 PUFAs have several opposing biological effects and influence white adipose tissue (WAT) function. The recent discovery of thermogenic UCP1-expressing brite adipocytes within WAT raised the question whether n-3 and n-6 PUFAs exert differential effects on brite adipocyte formation and mitochondrial function. Primary human preadipocytes were treated with n-3 PUFAs (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) or n-6 PUFA (arachidonic acid, ARA) during differentiation, and adipogenesis, white and brite gene expression markers, mitochondrial content and function were analyzed at day 12 of differentiation. Adipogenesis was equally increased by n-3 and n-6 PUFAs. The n-6 PUFA ARA increased lipid droplet size and expression of the white-specific marker TCF21 while decreased mitochondrial protein expression and respiratory function. In contrast, EPA increased expression of the brown adipocyte-related genes UCP1 and CPT1B, and improved mitochondrial function of adipocytes. The opposing effects of EPA and ARA on gene expression and mitochondrial function were also observed in cells treated from day 8 to 12 of adipocyte differentiation. EPA promotes brite adipogenesis and improves parameters of mitochondrial function, such as increased expression of CPTB1, citrate synthase activity and higher maximal respiratory capacity, while ARA reduced mitochondrial spare respiratory capacity in vitro. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Apparatus and method for polymer synthesis using arrays

DOEpatents

Brennan, Thomas M.

1995-01-01

A polymer synthesis apparatus (20) for building a polymer chain including a head assembly (21) having an array of nozzles (22) with each nozzle coupled to a reservoir (23) of liquid reagent (24) , and a base assembly (25) having an array of reaction wells (26). A transport mechanism (27) aligns the reaction wells (26) and selected nozzles (22) for deposition of the liquid reagent (24) into selected reaction wells (26). A sliding seal (30) is positioned between the head assembly (21) and the base assembly (25) to form a common chamber (31) enclosing both the reaction well (26) and the nozzles (22) therein. A gas inlet (70) into the common chamber (31), upstream from the nozzles (22), and a gas outlet (71) out of the common chamber (31) , downstream from the nozzles (22) , sweeps the common chamber ( 31 ) of toxic fumes emitted by the reagents. Each reaction well (26) includes an orifice (74) extending into the well (26) which is of a size and dimension to form a capillary liquid seal to retain the reagent solution (76) in the well (26) for polymer chain growth therein. A pressure regulating device (82) is provided for controlling a pressure differential, between a first gas pressure exerted on the reaction well (26) and a second gas pressure exerted on an exit (80) of the orifice, such that upon the pressure differential exceeding a predetermined amount, the reagent solution (76) is expelled from the well (26) through the orifice (74). A method of synthesis of a polymer chain in a synthesis apparatus (20) is also included.

Apparatus and method for polymer synthesis using arrays

DOEpatents

Brennan, Thomas M.

1996-01-01

A polymer synthesis apparatus (20) for building a polymer chain including a head assembly (21) having an array of nozzles (22) with each nozzle coupled to a reservoir (23) of liquid reagent (24), and a base assembly (25) having an array of reaction wells (26). A transport mechanism (27) aligns the reaction wells (26) and selected nozzles (22) for deposition of the liquid reagent (24) into selected reaction wells (26). A sliding seal (30) is positioned between the head assembly (21) and the base assembly (25) to form a common chamber (31) enclosing both the reaction well (26) and the nozzles (22) therein. A gas inlet (70) into the common chamber (31), upstream from the nozzles (22), and a gas outlet (71) out of the common chamber (31), downstream from the nozzles (22), sweeps the common chamber (31) of toxic fumes emitted by the reagents. Each reaction well ( 26) includes an orifice (74) extending into the well (26) which is of a size and dimension to form a capillary liquid seal to retain the reagent solution (76) in the well (26) for polymer chain growth therein. A pressure regulating device (82 ) is provided for controlling a pressure differential, between a first gas pressure exerted on the reaction well (26) and a second gas pressure exerted on an exit (80) of the orifice, such that upon the pressure differential exceeding a predetermined amount, the reagent solution (76) is expelled from the well (26) through the orifice (74). A method of synthesis of a polymer chain in a synthesis apparatus (20) is also included.

Relationships Between Internal and External Match-Load Indicators in Soccer Match Officials.

PubMed

Castillo, Daniel; Weston, Matthew; McLaren, Shaun J; Cámara, Jesús; Yanci, Javier

2017-08-01

The aims of this study were to describe the internal and external match loads (ML) of refereeing activity during official soccer matches and to investigate the relationship among the methods of ML quantification across a competitive season. A further aim was to examine the usefulness of differential perceived exertion (dRPE) as a tool for monitoring internal ML in soccer referees. Twenty field referees (FRs) and 43 assistant referees (ARs) participated in the study. Data were collected from 30 competitive matches (FR = 20 observations, AR = 43 observations) and included measures of internal (Edwards' heart-rate-derived training impulse [TRIMP EDW ]) ML, external (total distance covered, distance covered at high speeds, and player load) ML, and ML differentiated ratings of perceived respiratory (sRPE res ) and leg-muscle (sRPE mus ) exertion. Internal and external ML were all greater for FRs than for ARs (-19.7 to -72.5), with differences ranging from very likely very large to most likely extremely large. The relationships between internal-ML and external-ML indicators were, in most cases, unclear for FR (r < .35) and small to moderate for AR (r < .40). The authors found substantial differences between RPE res and RPE mus scores in both FRs (0.6 AU; ±90% confidence limits 0.4 AU) and ARs (0.4; ±0.3). These data demonstrate the multifaceted demands of soccer refereeing and thereby highlight the importance of monitoring both internal and external ML. Moreover, dRPE represents distinct dimensions of effort and may be useful in monitoring soccer referees' ML during official matches.

Quercetin Exerts Differential Neuroprotective Effects Against H2O2 and Aβ Aggregates in Hippocampal Neurons: the Role of Mitochondria.

PubMed

Godoy, Juan A; Lindsay, Carolina B; Quintanilla, Rodrigo A; Carvajal, Francisco J; Cerpa, Waldo; Inestrosa, Nibaldo C

2017-11-01

Amyloid-β peptide (Aβ) is one of the major players in the pathogenesis of Alzheimer's disease (AD). Despite numerous studies, the mechanisms by which Aβ induces neurodegeneration are not completely understood. Oxidative stress is considered a major contributor to the pathogenesis of AD, and accumulating evidence indicates that high levels of reactive oxygen species (ROS) are involved in Aβ-induced neurodegeneration. Moreover, Aβ can induce the deregulation of calcium homeostasis, which also affects mitochondrial function and triggers neuronal cell death. In the present study, we analyzed the effects of quercetin, a plant flavonoid with antioxidant properties, on oxidative stress- and Aβ-induced degeneration. Our results indicate that quercetin efficiently protected against H 2 O 2 -induced neuronal toxicity; however, this protection was only partial in rat hippocampal neurons that were treated with Aβ. Treatment with quercetin decreased ROS levels, recovered the normal morphology of mitochondria, and prevented mitochondrial dysfunction in neurons that were treated with H 2 O 2 . By contrast, quercetin treatment partially rescued hippocampal neurons from Aβ-induced mitochondrial injury. Most importantly, quercetin treatment prevented the toxic effects that are induced by H 2 O 2 in hippocampal neurons and, to a lesser extent, the Aβ-induced toxicity that is associated with the superoxide anion, which is a precursor of ROS production in mitochondria. Collectively, these results indicate that quercetin exerts differential effects on the prevention of H 2 O 2 - and Aβ-induced neurotoxicity in hippocampal neurons and may be a powerful tool for dissecting the molecular mechanisms underlying Aβ neurotoxicity.

Communal nesting exerts epigenetic influences on affective and social behaviors in rats selectively bred for an infantile trait.

PubMed

Martinez, Ashley Rae; Brunelli, Susan A; Zimmerberg, Betty

2015-02-01

Communal nesting (CN) is a mouse model of early social enrichment during pregnancy and lactation. In this study, a rat model of CN was developed to determine if CN exerts an epigenetic effect in rats selectively bred for an infantile affective trait (high and low rates of ultrasonic distress calls). High and Low offspring from CN groups were compared to standard reared (SN) offspring on five measures of social and affective behavior at three critical ages. A differential effect of the CN paradigm on High and Low lines was seen in measures of anxiety and arousal, but not in measures of depression or social behavior. Neonatal CN subjects emitted fewer distress calls than SN subjects when separated from their dams, and the High line subjects were more affected by the CN procedure. As juveniles, CN subjects showed increased social behaviors in tests of juvenile parenting and play compared to SN subjects. In adulthood, CN differentially increased the activity of Low line subjects. All CN subjects displayed less anxiety behavior in an open field compared to SN subjects; High line subjects were more anxious than Lows. CN reduced immobility and increased attempts to escape on the Porsolt forced swim task relative to SN subjects. These results extend the usefulness of this early enrichment paradigm from mice to rats, and found some rodent species differences in outcomes dependent on the behavioral test. They also emphasize the importance of social contact during pregnancy and lactation on offspring's optimal development across behaviors and ages. Copyright © 2014 Elsevier Inc. All rights reserved.

FAT1 cadherin acts upstream of Hippo signalling through TAZ to regulate neuronal differentiation.

PubMed

Ahmed, Abdulrzag F; de Bock, Charles E; Lincz, Lisa F; Pundavela, Jay; Zouikr, Ihssane; Sontag, Estelle; Hondermarck, Hubert; Thorne, Rick F

2015-12-01

The Hippo pathway is emerging as a critical nexus that balances self-renewal of progenitors against differentiation; however, upstream elements in vertebrate Hippo signalling are poorly understood. High expression of Fat1 cadherin within the developing neuroepithelium and the manifestation of severe neurological phenotypes in Fat1-knockout mice suggest roles in neurogenesis. Using the SH-SY5Y model of neuronal differentiation and employing gene silencing techniques, we show that FAT1 acts to control neurite outgrowth, also driving cells towards terminal differentiation via inhibitory effects on proliferation. FAT1 actions were shown to be mediated through Hippo signalling where it activated core Hippo kinase components and antagonised functions of the Hippo effector TAZ. Suppression of FAT1 promoted the nucleocytoplasmic shuttling of TAZ leading to enhanced transcription of the Hippo target gene CTGF together with accompanying increases in nuclear levels of Smad3. Silencing of TAZ reversed the effects of FAT1 depletion thus connecting inactivation of TAZ-TGFbeta signalling with Hippo signalling mediated through FAT1. These findings establish FAT1 as a new upstream Hippo element regulating early stages of differentiation in neuronal cells.

Lepidium meyenii (Maca) does not exert direct androgenic activities.

PubMed

Bogani, P; Simonini, F; Iriti, M; Rossoni, M; Faoro, F; Poletti, A; Visioli, F

2006-04-06

Maca is the edible root of the Peruvian plant Lepidum meyenii, traditionally employed for its purported aphrodisiac and fertility-enhancing properties. This study aimed at testing the hypothesis that Maca contains testosterone-like compounds, able to bind the human androgen receptor and promote transcription pathways regulated by steroid hormone signaling. Maca extracts (obtained with different solvents: methanol, ethanol, hexane and chloroform) are not able to regulate GRE (glucocorticoid response element) activation. Further experiments are needed to assess which compound, of the several Maca's components, is responsible of the observed in vivo effects.

An Evaluation of Computerized Tests as Predictors of Job Performance: II. Differential Validity for Global and Job Element Criteria. Final Report.

ERIC Educational Resources Information Center

Cory, Charles H.

This report presents data concerning the validity of a set of experimental computerized and paper-and-pencil tests for measures of on-job performance on global and job elements. It reports on the usefulness of 30 experimental and operational variables for predicting marks on 42 job elements and on a global criterion for Electrician's Mate,…

Concerning the sound insulation of building elements made up of light concretes. [acoustic absorption efficiency calculations

NASA Technical Reports Server (NTRS)

Giurgiu, I. I.

1974-01-01

The sound insulating capacity of building elements made up of light concretes is considered. Analyzing differentially the behavior of light concrete building elements under the influence of incident acoustic energy and on the basis of experimental measurements, coefficients of correction are introduced into the basic formulas for calculating the sound insulating capacity for the 100-3,2000 Hz frequency band.

Human olfactory bulb neural stem cells expressing hNGF restore cognitive deficit in Alzheimer's disease rat model.

PubMed

Marei, Hany E S; Farag, Amany; Althani, Asma; Afifi, Nahla; Abd-Elmaksoud, Ahmed; Lashen, Samah; Rezk, Shaymaa; Pallini, Roberto; Casalbore, Patrizia; Cenciarelli, Carlo

2015-01-01

In this study, we aim to demonstrate the fate of allogenic adult human olfactory bulb neural stem/progenitor cells (OBNSC/NPCs) transplanted into the rat hippocampus treated with ibotenic acid (IBO), a neurotoxicant specific to hippocampal cholinergic neurons that are lost in Alzheimer's disease. We assessed their possible ability to survive, integrate, proliferate, and differentiate into different neuronal and glial elements: we also evaluate their possible therapeutic potential, and the mechanism(s) relevant to neuroprotection following their engraftment into the CNS milieu. OBNSC/NPCs were isolated from adult human olfactory bulb patients, genetically engineered to express GFP and human nerve growth factor (hNGF) by lentivirus-mediated infection, and stereotaxically transplanted into the hippocampus of IBO-treated animals and controls. Stereological analysis of engrafted OBNSCs eight weeks post transplantation revealed a 1.89 fold increase with respect to the initial cell population, indicating a marked ability for survival and proliferation. In addition, 54.71 ± 11.38%, 30.18 ± 6.00%, and 15.09 ± 5.38% of engrafted OBNSCs were identified by morphological criteria suggestive of mature neurons, oligodendrocytes and astrocytes respectively. Taken together, this work demonstrated that human OBNSCs expressing NGF ameliorate the cognitive deficiencies associated with IBO-induced lesions in AD model rats, and the improvement can probably be attributed primarily to neuronal and glial cell replacement as well as the trophic influence exerted by the secreted NGF. © 2014 Wiley Periodicals, Inc.

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

Gemelli, Claudia, E-mail: claudia.gemelli@unimore.it; Center for Regenerative Medicine, University of Modena and Reggio Emilia, Via Gottardi 100, 41125 Modena; Martello, Andrea

Orosomucoid 1 (ORM1), also named Alpha 1 acid glycoprotein A (AGP-A), is an abundant plasma protein characterized by anti-inflammatory and immune-modulating properties. The present study was designed to identify a possible correlation between ORM1 and Vitamin D3 (1,25(OH)2D3), a hormone exerting a widespread effect on cell proliferation, differentiation and regulation of the immune system. In particular, the data described here indicated that ORM1 is a 1,25(OH)2D3 primary response gene, characterized by the presence of a VDRE element inside the 1 kb sequence of its proximal promoter region. This finding was demonstrated with gene expression studies, Chromatin Immunoprecipitation and luciferase transactivationmore » experiments and confirmed by VDR full length and dominant negative over-expression. In addition, several experiments carried out in human normal monocytes demonstrated that the 1,25(OH)2D3 – VDR – ORM1 pathway plays a functional role inside the macrophage de-activation process and that ORM1 may be considered as a signaling molecule involved in the maintenance of tissue homeostasis and remodeling. - Highlights: • ORM1 is a Vitamin D primary response gene. • VD and its receptor VDR are involved in the de-activation process mediated by human resident macrophages. • The signaling pathway VD-VDR-ORM1 plays an important role in the control of macrophage de-activation process. • ORM1 may be defined as a signaling molecule implicated in the maintenance of tissue homeostasis and remodeling.« less

[Principal component analysis and cluster analysis of inorganic elements in sea cucumber Apostichopus japonicus].

PubMed

Liu, Xiao-Fang; Xue, Chang-Hu; Wang, Yu-Ming; Li, Zhao-Jie; Xue, Yong; Xu, Jie

2011-11-01

The present study is to investigate the feasibility of multi-elements analysis in determination of the geographical origin of sea cucumber Apostichopus japonicus, and to make choice of the effective tracers in sea cucumber Apostichopus japonicus geographical origin assessment. The content of the elements such as Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Mo, Cd, Hg and Pb in sea cucumber Apostichopus japonicus samples from seven places of geographical origin were determined by means of ICP-MS. The results were used for the development of elements database. Cluster analysis(CA) and principal component analysis (PCA) were applied to differentiate the sea cucumber Apostichopus japonicus geographical origin. Three principal components which accounted for over 89% of the total variance were extracted from the standardized data. The results of Q-type cluster analysis showed that the 26 samples could be clustered reasonably into five groups, the classification results were significantly associated with the marine distribution of the sea cucumber Apostichopus japonicus samples. The CA and PCA were the effective methods for elements analysis of sea cucumber Apostichopus japonicus samples. The content of the mineral elements in sea cucumber Apostichopus japonicus samples was good chemical descriptors for differentiating their geographical origins.

Bovine lactoferrin and lactoferricin exert antitumor activities on human colorectal cancer cells (HT-29) by activating various signaling pathways.

PubMed

Jiang, Rulan; Lönnerdal, Bo

2017-02-01

Lactoferrin (Lf) is an iron-binding glycoprotein that is present at high concentrations in milk. Bovine lactoferricin (LfcinB) is a peptide fragment generated by pepsin proteolysis of bovine lactoferrin (bLf). LfcinB consists of amino acid residues 17-41 proximal to the N-terminus of bLf and a disulfide bond between residues 19 and 36, forming a loop. Both bLf and LfcinB have been demonstrated to have antitumor activities. Colorectal cancer is the second most common cause of cancer death in developed countries. We hypothesized that bLf and LfcinB exert antitumor activities on colon cancer cells (HT-29) by triggering various signaling pathways. bLf and LfcinB significantly induced apoptosis in HT-29 cells but not in normal human intestinal epithelial cells, as revealed by the ApoTox-Glo Triplex Assay. The LIVE/DEAD cell viability assay showed that both bLf and LfcinB reduced the viability of HT-29 cells. Transcriptome analysis indicated that bLf, cyclic LfcinB, and linear LfcinB exerted antitumor activities by differentially activating diverse signaling pathways, including p53, apoptosis, and angiopoietin signaling. Immunoblotting results confirmed that both bLf and LfcinBs increased expression of caspase-8, p53, and p21, critical proteins in tumor suppression. These results provide valuable information regarding bLf and LfcinB for potential clinical applications in colon cancer therapy.

Acute loss of TET function results in aggressive myeloid cancer in mice

PubMed Central

An, Jungeun; González-Avalos, Edahí; Chawla, Ashu; Jeong, Mira; López-Moyado, Isaac F.; Li, Wei; Goodell, Margaret A.; Chavez, Lukas; Ko, Myunggon; Rao, Anjana

2015-01-01

TET-family dioxygenases oxidize 5-methylcytosine (5mC) in DNA, and exert tumour suppressor activity in many types of cancers. Even in the absence of TET coding region mutations, TET loss-of-function is strongly associated with cancer. Here we show that acute elimination of TET function induces the rapid development of an aggressive, fully-penetrant and cell-autonomous myeloid leukaemia in mice, pointing to a causative role for TET loss-of-function in this myeloid malignancy. Phenotypic and transcriptional profiling shows aberrant differentiation of haematopoietic stem/progenitor cells, impaired erythroid and lymphoid differentiation and strong skewing to the myeloid lineage, with only a mild relation to changes in DNA modification. We also observe progressive accumulation of phospho-H2AX and strong impairment of DNA damage repair pathways, suggesting a key role for TET proteins in maintaining genome integrity. PMID:26607761

Differential cytotoxicity of MEX: a component of Neem oil whose action is exerted at the cell membrane level.

PubMed

Ricci, Francesca; Berardi, Valerio; Risuleo, Gianfranco

2008-12-31

Neem oil is obtained from the seeds of the tree Azadirachta indica. Its chemical composition is very complex, being rich in terpenoids and limonoids, as well as volatile sulphur modified compounds. This work focused on the evaluation of a component of the whole Neem oil obtained by methanolic extraction and defined as MEX. Cytotoxicity was assessed on two different cell populations: a stabilized murine fibroblast line (3T6) and a tumor cell line (HeLa). The data presented here suggest a differential sensitivity of these two populations, the tumor line exhibiting a significantly higher sensitivity to MEX. The data strongly suggest that its toxic target is the cell membrane. In addition the results presented here imply that MEX may contain one or more agents that could find a potential use in anti-proliferative therapy.

Crossroads of Wnt and Hippo in epithelial tissues.

PubMed

Bernascone, Ilenia; Martin-Belmonte, Fernando

2013-08-01

Epithelial tissues undergo constant growth and differentiation during embryonic development and to replace damaged tissue in adult organs. These processes are governed by different signaling pathways that ultimately control the expression of genes associated with cell proliferation, patterning, and death. One essential pathway is Wnt, which controls tubulogenesis in several epithelial organs. Recently, Wnt has been closely linked to other signaling pathways, such as Hippo, that orchestrate proliferation and apoptosis to control organ size. There is evidence that epithelial cell junctions may sequester the transcription factors that act downstream of these signaling pathways, which would represent an important aspect of their functional regulation and their influence on cell behavior. Here, we review the transcriptional control exerted by the Wnt and Hippo signaling pathways during epithelial growth, patterning, and differentiation and recent advances in understanding of the regulation and crosstalk of these pathways in epithelial tissues. Copyright © 2013 Elsevier Ltd. All rights reserved.

Extracellular matrix as a solid-state regulator in angiogenesis: identification of new targets for anti-cancer therapy

NASA Technical Reports Server (NTRS)

Ingber, D. E.

1992-01-01

Angiogenesis, the growth of blood capillaries, is regulated by soluble growth factors and insoluble extracellular matrix (ECM) molecules. Soluble angiogenic mitogens act over large distances to initiate capillary growth whereas changes in ECM govern whether individual cells will grow, differentiate, or involute in response to these stimuli in the local tissue microenvironment. Analysis of this local control mechanism has revealed that ECM molecules switch capillary endothelial cells between differentiation and growth by both binding specific transmembrane integrin receptors and physically resisting cell-generated mechanical loads that are applied to these receptors. Control of capillary endothelial cell form and function therefore may be exerted by altering the mechanical properties of the ECM as well as its chemical composition. Understanding of this mechanochemical control mechanism has led to the development of new angiogenesis inhibitors that may be useful for the treatment of cancer.

New factors controlling the balance between osteoblastogenesis and adipogenesis.

PubMed

Abdallah, Basem M; Kassem, Moustapha

2012-02-01

The majority of conditions associated with bone loss, including aging, are accompanied by increased marrow adiposity possibly due to shifting of the balance between osteoblast and adipocyte differentiation in bone marrow stromal (skeletal) stem cells (MSC). In order to study the relationship between osteoblastogenesis and adipogenesis in bone marrow, we have characterized cellular models of multipotent MSC as well as pre-osteoblastic and pre-adipocytic cell populations. Using these models, we identified two secreted factors in the bone marrow microenviroment: secreted frizzled-related protein 1 (sFRP-1) and delta-like1 (preadipocyte factor 1) (Dlk1/Pref-1). Both exert regulatory effects on osteoblastogenesis and adipogenesis. Our studies suggest a model for lineage fate determination of MSC that is regulated through secreted factors in the bone marrow microenvironment that mediate a cross-talk between lineage committed cell populations in addition to controlling differentiation choices of multipotent MSC. Copyright © 2011 Elsevier Inc. All rights reserved.

Biocybernetic factors in human perception and memory

NASA Technical Reports Server (NTRS)

Lai, D. C.

1975-01-01

The objective of this research is to develop biocybernetic techniques for use in the analysis and development of skills required for the enhancement of concrete images of the 'eidetic' type. The scan patterns of the eye during inspection of scenes are treated as indicators of the brain's strategy for the intake of visual information. The authors determine the features that differentiate visual scan patterns associated with superior imagery from scan patterns associated with inferior imagery, and simultaneously differentiate the EEG features correlated with superior imagery from those correlated with inferior imagery. A closely-coupled man-machine system has been designed to generate image enhancement and to train the individual to exert greater voluntary control over his own imagery. The models for EEG signals and saccadic eye movement in the man-machine system have been completed. The report describes the details of these models and discusses their usefulness.

Glucose availability controls adipogenesis in mouse 3T3-L1 adipocytes via up-regulation of nicotinamide metabolism.

PubMed

Jackson, Robert M; Griesel, Beth A; Gurley, Jami M; Szweda, Luke I; Olson, Ann Louise

2017-11-10

Expansion of adipose tissue in response to a positive energy balance underlies obesity and occurs through both hypertrophy of existing cells and increased differentiation of adipocyte precursors (hyperplasia). To better understand the nutrient signals that promote adipocyte differentiation, we investigated the role of glucose availability in regulating adipocyte differentiation and maturation. 3T3-L1 preadipocytes were grown and differentiated in medium containing a standard differentiation hormone mixture and either 4 or 25 mm glucose. Adipocyte maturation at day 9 post-differentiation was determined by key adipocyte markers, including glucose transporter 4 (GLUT4) and adiponectin expression and Oil Red O staining of neutral lipids. We found that adipocyte differentiation and maturation required a pulse of 25 mm glucose only during the first 3 days of differentiation. Importantly, fatty acids were unable to substitute for the 25 mm glucose pulse during this period. The 25 mm glucose pulse increased adiponectin and GLUT4 expression and accumulation of neutral lipids via distinct mechanisms. Adiponectin expression and other early markers of differentiation required an increase in the intracellular pool of total NAD/P. In contrast, GLUT4 protein expression was only partially restored by increased NAD/P levels. Furthermore, GLUT4 mRNA expression was mediated by glucose-dependent activation of GLUT4 gene transcription through the cis-acting GLUT4-liver X receptor element (LXRE) promoter element. In summary, this study supports the conclusion that high glucose promotes adipocyte differentiation via distinct metabolic pathways and independently of fatty acids. This may partly explain the mechanism underlying adipocyte hyperplasia that occurs much later than adipocyte hypertrophy in the development of obesity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Measuring perception of elements in outdoor environments

Treesearch

George H. Moeller; Robert MacLachlan; Douglas A. Morrison

1974-01-01

The meanings of 10 concepts that describe elements of natural outdoor environments were measured with the semantic differential technique. Each concept was evaluated on three factors of meaning - evaluation, potency, and activity. Sixty recreationists were surveyed from each of three user groups - campers, picnickers, and wilderness hikers. Similarities and differences...

Adjudin, a potential male contraceptive, exerts its effects locally in the seminiferous epithelium of mammalian testes.

PubMed

Mok, Ka-Wai; Mruk, Dolores D; Lie, Pearl P Y; Lui, Wing-Yee; Cheng, C Yan

2011-05-01

Adjudin is a derivative of 1H-indazole-3-carboxylic acid that was shown to have potent anti-spermatogenic activity in rats, rabbits, and dogs. It exerts its effects most notably locally in the apical compartment of the seminiferous epithelium, behind the blood-testis barrier, by disrupting adhesion of germ cells, most notably spermatids to the Sertoli cells, thereby inducing release of immature spermatids from the epithelium that leads to infertility. After adjudin is metabolized, the remaining spermatogonial stem cells and spermatogonia repopulate the seminiferous epithelium gradually via spermatogonial self-renewal and differentiation, to be followed by meiosis and spermiogenesis, and thus fertility rebounds. Recent studies in rats have demonstrated unequivocally that the primary and initial cellular target of adjudin in the testis is the apical ectoplasmic specialization, a testis-specific anchoring junction type restricted to the interface between Sertoli cells and elongating spermatids (from step 8 to 19 spermatids). In this review, we highlight some of the recent advances and obstacles regarding the possible use of adjudin as a male contraceptive.

Adjudin, a potential male contraceptive, exerts its effects locally in the seminiferous epithelium of mammalian testes

PubMed Central

Mok, Ka-Wai; Mruk, Dolores D; Lie, Pearl P Y; Lui, Wing-Yee; Cheng, C Yan

2015-01-01

Adjudin is a derivative of 1H-indazole-3-carboxylic acid that was shown to have potent anti-spermatogenic activity in rats, rabbits, and dogs. It exerts its effects most notably locally in the apical compartment of the seminiferous epithelium, behind the blood–testis barrier, by disrupting adhesion of germ cells, most notably spermatids to the Sertoli cells, thereby inducing release of immature spermatids from the epithelium that leads to infertility. After adjudin is metabolized, the remaining spermatogonial stem cells and spermatogonia repopulate the seminiferous epithelium gradually via spermatogonial self-renewal and differentiation, to be followed by meiosis and spermiogenesis, and thus fertility rebounds. Recent studies in rats have demonstrated unequivocally that the primary and initial cellular target of adjudin in the testis is the apical ectoplasmic specialization, a testis-specific anchoring junction type restricted to the interface between Sertoli cells and elongating spermatids (from step 8 to 19 spermatids). In this review, we highlight some of the recent advances and obstacles regarding the possible use of adjudin as a male contraceptive. PMID:21307270

Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

PubMed Central

Oláh, Attila; Tóth, Balázs I.; Borbíró, István; Sugawara, Koji; Szöllõsi, Attila G.; Czifra, Gabriella; Pál, Balázs; Ambrus, Lídia; Kloepper, Jennifer; Camera, Emanuela; Ludovici, Matteo; Picardo, Mauro; Voets, Thomas; Zouboulis, Christos C.; Paus, Ralf; Bíró, Tamás

2014-01-01

The endocannabinoid system (ECS) regulates multiple physiological processes, including cutaneous cell growth and differentiation. Here, we explored the effects of the major nonpsychotropic phytocannabinoid of Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland function and determined that CBD behaves as a highly effective sebostatic agent. Administration of CBD to cultured human sebocytes and human skin organ culture inhibited the lipogenic actions of various compounds, including arachidonic acid and a combination of linoleic acid and testosterone, and suppressed sebocyte proliferation via the activation of transient receptor potential vanilloid-4 (TRPV4) ion channels. Activation of TRPV4 interfered with the prolipogenic ERK1/2 MAPK pathway and resulted in the downregulation of nuclear receptor interacting protein-1 (NRIP1), which influences glucose and lipid metabolism, thereby inhibiting sebocyte lipogenesis. CBD also exerted complex antiinflammatory actions that were coupled to A2a adenosine receptor-dependent upregulation of tribbles homolog 3 (TRIB3) and inhibition of the NF-κB signaling. Collectively, our findings suggest that, due to the combined lipostatic, antiproliferative, and antiinflammatory effects, CBD has potential as a promising therapeutic agent for the treatment of acne vulgaris. PMID:25061872

Boosting antitumor responses of T lymphocytes infiltrating human prostate cancers.

PubMed

Bronte, Vincenzo; Kasic, Tihana; Gri, Giorgia; Gallana, Keti; Borsellino, Giovanna; Marigo, Ilaria; Battistini, Luca; Iafrate, Massimo; Prayer-Galetti, Tommaso; Pagano, Francesco; Viola, Antonella

2005-04-18

Immunotherapy may provide valid alternative therapy for patients with hormone-refractory metastatic prostate cancer. However, if the tumor environment exerts a suppressive action on antigen-specific tumor-infiltrating lymphocytes (TIL), immunotherapy will achieve little, if any, success. In this study, we analyzed the modulation of TIL responses by the tumor environment using collagen gel matrix-supported organ cultures of human prostate carcinomas. Our results indicate that human prostatic adenocarcinomas are infiltrated by terminally differentiated cytotoxic T lymphocytes that are, however, in an unresponsive status. We demonstrate the presence of high levels of nitrotyrosines in prostatic TIL, suggesting a local production of peroxynitrites. By inhibiting the activity of arginase and nitric oxide synthase, key enzymes of L-arginine metabolism that are highly expressed in malignant but not in normal prostates, reduced tyrosine nitration and restoration of TIL responsiveness to tumor were achieved. The metabolic control exerted by the tumor on TIL function was confirmed in a transgenic mouse prostate model, which exhibits similarities with human prostate cancer. These results identify a novel and dominant mechanism by which cancers induce immunosuppression in situ and suggest novel strategies for tumor immunotherapy.

Zoledronic acid modulates maturation of human monocyte-derived dendritic cells.

PubMed

Orsini, Giulia; Failli, Alessandra; Legitimo, Annalisa; Adinolfi, Barbara; Romanini, Antonella; Consolini, Rita

2011-12-01

Zoledronic acid (ZA) is a drug of the bisphosphonate class, which is widely used for the treatment of both osteoporosis and skeletal metastasis. Besides its main bone antiresorptive activity, ZA displays antitumor properties, by triggering the expansion and activation of γδ T-cells, which exert an antitumor effect through dendritic cells (DCs). Several studies have reported the interaction between ZA and γδ T-cells, but the potential immunoregulatory activity of this drug on DCs has scarcely been investigated. Therefore, in this paper, we evaluated the effects of a therapeutic dose of ZA on the in vitro generation and maturation of DCs derived from peripheral blood monocytes of healthy adult donors. We demonstrate that ZA treatment did not affect DC differentiation, but inhibited DC maturation on lipopolysaccharide activation, as shown by the impaired expression of maturation surface markers and reduced ability to induce allogeneic T-cell proliferation. Interestingly, IL-10 secretion by mature DCs was significantly lower in ZA-treated cells than in controls. We conclude that ZA exerts its immunological in vitro activity also by modulating the maturation of DCs.

Riddles about the origin and thermal history of the moon

NASA Technical Reports Server (NTRS)

Levin, B. Y.; Mayeva, S. V.

1977-01-01

Magmatic differentiation of the moon's interior, confirmed through calculations of thermal history, was studied. It appears that differentiation was a result of the moon's initial temperature whose origin remains unknown. In solving this problem, convective models of the moon were considered as well as a two layered differentiated model of the moon, operative over the past 3.5 billion years. The high content of long lived radioactive elements present was investigated in explaining the moon's current thermal properties. The controversy concerning the true nature of magmatic differentiation continues to be unsolved.

K/TH in Achondrites and Interpretation of Grand Data for the Dawn Mission

NASA Technical Reports Server (NTRS)

Usui, T.; McSween, H. Y., Jr.; Mittlefehldt, D. W.; Prettyman, T. H.

2008-01-01

The Dawn mission will explore 4 Vesta [1], a highly differentiated asteroid believed to be the parent body of the howardite, eucrite and diogenite (HED) meteorite suite [e.g. 2]. The Dawn spacecraft is equipped with a gamma-ray and neutron detector (GRaND), which will enable measurement and mapping of elemental abundances on Vesta s surface [3]. Drawing on HED geochemistry, Usui and McSween [4] proposed a linear mixing model for interpretation of GRaND data. However, the HED suite is not the only achondrite suite representing asteroidal basaltic crusts; others include the mesosiderites, angrites, NWA 011, and possibly Ibitira, each of which is thought to have a distinct parental asteroid [5]. Here we critically examine the variability of GRaND-analyzed elements, K and Th, in HED meteorites, and propose a method based on the K-Th systematics to distinguish between HED and the other differentiated achondrites. Maps of these elements might also recognize incompatible element enriched areas such as mapped locally on the Moon (KREEP) [6], and variations in K/Th ratios might indicate impact volatilization of K. We also propose a new mixing model using elements that will be most reliably measured by GRaND, including K.

Load-Differential Features for Automated Detection of Fatigue Cracks Using Guided Waves (Preprint)

DTIC Science & Technology

2011-11-01

AFRL-RX-WP-TP-2011-4363 LOAD-DIFFERENTIAL FEATURES FOR AUTOMATED DETECTION OF FATIGUE CRACKS USING GUIDED WAVES (PREPRINT) Jennifer E...AUTOMATED DETECTION OF FATIGUE CRACKS USING GUIDED WAVES (PREPRINT) 5a. CONTRACT NUMBER FA8650-09-C-5206 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER...tensile loads open fatigue cracks and thus enhance their detectability using ultrasonic methods. Here we introduce a class of load-differential methods

Survey of the status of finite element methods for partial differential equations

NASA Technical Reports Server (NTRS)

Temam, Roger

1986-01-01

The finite element methods (FEM) have proved to be a powerful technique for the solution of boundary value problems associated with partial differential equations of either elliptic, parabolic, or hyperbolic type. They also have a good potential for utilization on parallel computers particularly in relation to the concept of domain decomposition. This report is intended as an introduction to the FEM for the nonspecialist. It contains a survey which is totally nonexhaustive, and it also contains as an illustration, a report on some new results concerning two specific applications, namely a free boundary fluid-structure interaction problem and the Euler equations for inviscid flows.

Application of the Finite Element Method in Atomic and Molecular Physics

NASA Technical Reports Server (NTRS)

Shertzer, Janine

2007-01-01

The finite element method (FEM) is a numerical algorithm for solving second order differential equations. It has been successfully used to solve many problems in atomic and molecular physics, including bound state and scattering calculations. To illustrate the diversity of the method, we present here details of two applications. First, we calculate the non-adiabatic dipole polarizability of Hi by directly solving the first and second order equations of perturbation theory with FEM. In the second application, we calculate the scattering amplitude for e-H scattering (without partial wave analysis) by reducing the Schrodinger equation to set of integro-differential equations, which are then solved with FEM.

Differential distribution of proteins expressed in companion cells in the sieve element-companion cell complex of rice plants.

PubMed

Fukuda, Akari; Fujimaki, Syu; Mori, Tomoko; Suzui, Nobuo; Ishiyama, Keiki; Hayakawa, Toshihiko; Yamaya, Tomoyuki; Fujiwara, Toru; Yoneyama, Tadakatsu; Hayashi, Hiroaki

2005-11-01

Sieve tubes are comprised of sieve elements, enucleated cells that are incapable of RNA and protein synthesis. The proteins in sieve elements are supplied from the neighboring companion cells through plasmodesmata. In rice plants, it was unclear whether or not all proteins produced in companion cells had the same distribution pattern in the sieve element-companion cell complex. In this study, the distribution pattern of four proteins, beta-glucuronidase (GUS), green fluorescent protein (GFP), thioredoxin h (TRXh) and glutathione S-transferase (GST) were analyzed. The foreign proteins GUS and GFP were expressed in transgenic rice plants under the control of the TRXh gene promoter (PTRXh), a companion cell-specific promoter. Analysis of leaf cross-sections of PTRXh-GUS and PTRXh-GFP plants indicated high accumulation of GUS and GFP, respectively, in companion cells rather than in sieve elements. GUS and GFP were also detected in phloem sap collected from leaf sheaths of the transgenic rice plants, suggesting these proteins could enter sieve elements. Relative amounts of GFP and endogenous phloem proteins, TRXh and GST, in phloem sap and total leaf extracts were compared. Compared to TRXh and GST, GFP content was higher in total leaf extracts, but lower in phloem sap, suggesting that GFP accumulated mainly in companion cells rather than in sieve elements. On the other hand, TRXh and GST appeared to accumulate in sieve elements rather than in companion cells. These results indicate the evidence for differential distribution of proteins between sieve elements and companion cells in rice plants.

Efficacy of Pulsed-Field Gel Electrophoresis and Repetitive Element Sequence-Based PCR in Typing of Salmonella Isolates from Assam, India.

PubMed

Gogoi, Purnima; Borah, Probodh; Hussain, Iftikar; Das, Leena; Hazarika, Girin; Tamuly, Shantanu; Barkalita, Luit Moni

2018-05-01

A total of 12 Salmonella isolates belonging to different serovars, viz , Salmonella enterica serovar Enteritidis ( n = 4), Salmonella enterica serovar Weltevreden ( n = 4), Salmonella enterica serovar Newport ( n = 1), Salmonella enterica serovar Litchifield ( n = 1), and untypeable strains ( n = 2) were isolated from 332 diarrheic fecal samples collected from animals, birds, and humans. Of the two molecular typing methods applied, viz , repetitive element sequence-based PCR (REP-PCR) and pulsed-field gel electrophoresis (PFGE), PFGE could clearly differentiate the strains belonging to different serovars as well as differentiate between strains of the same serovar with respect to their source of isolation, whereas REP-PCR could not differentiate between strains of the same serovar. Thus, it can be suggested that PFGE is more useful and appropriate for molecular typing of Salmonella isolates during epidemiological investigations than REP-PCR. Copyright © 2018 American Society for Microbiology.

Gastrodia and Uncaria (tianma gouteng) water extract exerts antioxidative and antiapoptotic effects against cerebral ischemia in vitro and in vivo.

PubMed

Xian, Jia Wen; Choi, Angus Yiu-Ting; Lau, Clara Bik-San; Leung, Wing Nang; Ng, Chun Fai; Chan, Chun Wai

2016-01-01

Gastrodia and Uncaria decoction (tianma gouteng yin) is commonly used in Chinese medicine to treat cerebral ischemia. The aim of this study was to investigate the neuroprotective effects of a water extract (GUW) of Gastrodia elata (tianma; GE) and Uncaria rhynchophylla (gouteng; UR) against ischemic insult using oxygen-glucose-deprived neuronal differentiated PC12 cells and rats subjected to middle cerebral artery occlusion (MCAO). GUW was prepared by boiling raw GE and UR in water, followed by the lyophilization of the resulting extract. Neuronal differentiated PC12 cells were subjected to oxygen-glucose deprivation with or without GUW. The neuroprotective effects of GUW were compared with those of the corresponding GE and UR extracts to tease apart the effects of the different herbs. The synergistic effect of GE and UR in GUW was measured using a modified version of Burgi's formulae. The neuroprotective mechanisms via Nrf2 and anti-apoptotic pathways were investigated using real time PCR and enzyme activity assays. The neuroprotective effects of GUW were studied in vivo using a rat MCAO model. Neurofunctional outcome and brain infarct volume we assessed. H&E staining, cresyl violet staining and immunohistochemistry were performed to assess the histological outcome. The results of lactate dehydrogenase assay showed that GUW protected cells in a concentration-dependent manner (P < 0.001). Moreover, the neuroprotective effects of GUW were greater than those of GE + UR (P = 0.018). Burgi's formula showed that the herbs in GUW acted synergistically to protect cells from ischemic injury. GUW significantly upregulated Bcl-2 expression (P = 0.0130) and reduced caspase-3 activity by 60 % (P < 0.001). GUW upregulated Nrf-2 expression (P = 0.0066) and the antioxidant response element pathway genes. The infarct volume was reduced by 55 % at day 7 of reperfusion (P < 0.001), and significant improvements were observed in the neurological deficit score and beam-walking test at 7 days (P < 0.001). H&E and cresyl violet staining revealed higher tissue integrity in the GUW treatment group compared with MCAO rats. GUW modulated the antioxidant system and antiapoptotic genes in oxygen-glucose deprived neuronal differentiated PC12 cells and MCAO sprague-dawley rats.

Defined spatiotemporal features of RAS-ERK signals dictate cell fate in MCF-7 mammary epithelial cells

PubMed Central

Herrero, Ana; Casar, Berta; Colón-Bolea, Paula; Agudo-Ibáñez, Lorena; Crespo, Piero

2016-01-01

Signals conveyed through the RAS-ERK pathway are essential for the determination of cell fate. It is well established that signal variability is achieved in the different microenvironments in which signals unfold. It is also known that signal duration is critical for decisions concerning cell commitment. However, it is unclear how RAS-ERK signals integrate time and space in order to elicit a given biological response. To investigate this, we used MCF-7 cells, in which EGF-induced transient ERK activation triggers proliferation, whereas sustained ERK activation in response to heregulin leads to adipocytic differentiation. We found that both proliferative and differentiating signals emanate exclusively from plasma membrane–disordered microdomains. Of interest, the EGF signal can be transformed into a differentiating stimulus by HRAS overexpression, which prolongs ERK activation, but only if HRAS localizes at disordered membrane. On the other hand, HRAS signals emanating from the Golgi complex induce apoptosis and can prevent heregulin-induced differentiation. Our results indicate that within the same cellular context, RAS can exert different, even antagonistic, effects, depending on its sublocalization. Thus cell destiny is defined by the ability of a stimulus to activate RAS at the appropriate sublocalization for an adequate period while avoiding switching on opposing RAS signals. PMID:27099370

A WNT/beta-catenin signaling activator, R-spondin, plays positive regulatory roles during skeletal myogenesis.

PubMed

Han, Xiang Hua; Jin, Yong-Ri; Seto, Marianne; Yoon, Jeong Kyo

2011-03-25

R-spondins (RSPOs) are a recently characterized family of secreted proteins that activate WNT/β-catenin signaling. In this study, we investigated the potential roles of the RSPO proteins during myogenic differentiation. Overexpression of the Rspo1 gene or administration of recombinant RSPO2 protein enhanced mRNA and protein expression of a basic helix-loop-helix (bHLH) class myogenic determination factor, MYF5, in both C2C12 myoblasts and primary satellite cells, whereas MYOD or PAX7 expression was not affected. RSPOs also promoted myogenic differentiation and induced hypertrophic myotube formation in C2C12 cells. In addition, Rspo2 and Rspo3 gene knockdown by RNA interference significantly compromised MYF5 expression, myogenic differentiation, and myotube formation. Furthermore, Myf5 expression was reduced in the developing limbs of mouse embryos lacking the Rspo2 gene. Finally, we demonstrated that blocking of WNT/β-catenin signaling by DKK1 or a dominant-negative form of TCF4 reversed MYF5 expression, myogenic differentiation, and hypertrophic myotube formation induced by RSPO2, indicating that RSPO2 exerts its activity through the WNT/β-catenin signaling pathway. Our results provide strong evidence that RSPOs are key positive regulators of skeletal myogenesis acting through the WNT/β-catenin signaling pathway.

A WNT/β-Catenin Signaling Activator, R-spondin, Plays Positive Regulatory Roles during Skeletal Myogenesis*

PubMed Central

Han, Xiang Hua; Jin, Yong-Ri; Seto, Marianne; Yoon, Jeong Kyo

2011-01-01

R-spondins (RSPOs) are a recently characterized family of secreted proteins that activate WNT/β-catenin signaling. In this study, we investigated the potential roles of the RSPO proteins during myogenic differentiation. Overexpression of the Rspo1 gene or administration of recombinant RSPO2 protein enhanced mRNA and protein expression of a basic helix-loop-helix (bHLH) class myogenic determination factor, MYF5, in both C2C12 myoblasts and primary satellite cells, whereas MYOD or PAX7 expression was not affected. RSPOs also promoted myogenic differentiation and induced hypertrophic myotube formation in C2C12 cells. In addition, Rspo2 and Rspo3 gene knockdown by RNA interference significantly compromised MYF5 expression, myogenic differentiation, and myotube formation. Furthermore, Myf5 expression was reduced in the developing limbs of mouse embryos lacking the Rspo2 gene. Finally, we demonstrated that blocking of WNT/β-catenin signaling by DKK1 or a dominant-negative form of TCF4 reversed MYF5 expression, myogenic differentiation, and hypertrophic myotube formation induced by RSPO2, indicating that RSPO2 exerts its activity through the WNT/β-catenin signaling pathway. Our results provide strong evidence that RSPOs are key positive regulators of skeletal myogenesis acting through the WNT/β-catenin signaling pathway. PMID:21252233

Prospero-related homeobox 1 (Prox1) at the crossroads of diverse pathways during adult neural fate specification

PubMed Central

Stergiopoulos, Athanasios; Elkouris, Maximilianos; Politis, Panagiotis K.

2015-01-01

Over the last decades, adult neurogenesis in the central nervous system (CNS) has emerged as a fundamental process underlying physiology and disease. Recent evidence indicates that the homeobox transcription factor Prox1 is a critical intrinsic regulator of neurogenesis in the embryonic CNS and adult dentate gyrus (DG) of the hippocampus, acting in multiple ways and instructed by extrinsic cues and intrinsic factors. In the embryonic CNS, Prox1 is mechanistically involved in the regulation of proliferation vs. differentiation decisions of neural stem cells (NSCs), promoting cell cycle exit and neuronal differentiation, while inhibiting astrogliogenesis. During the complex differentiation events in adult hippocampal neurogenesis, Prox1 is required for maintenance of intermediate progenitors (IPs), differentiation and maturation of glutamatergic interneurons, as well as specification of DG cell identity over CA3 pyramidal fate. The mechanism by which Prox1 exerts multiple functions involves distinct signaling pathways currently not fully highlighted. In this mini-review, we thoroughly discuss the Prox1-dependent phenotypes and molecular pathways in adult neurogenesis in relation to different upstream signaling cues and cell fate determinants. In addition, we discuss the possibility that Prox1 may act as a cross-talk point between diverse signaling cascades to achieve specific outcomes during adult neurogenesis. PMID:25674048

Indirect Self-Destructiveness and Emotional Intelligence.

PubMed

Tsirigotis, Konstantinos

2016-06-01

While emotional intelligence may have a favourable influence on the life and psychological and social functioning of the individual, indirect self-destructiveness exerts a rather negative influence. The aim of this study has been to explore possible relations between indirect self-destructiveness and emotional intelligence. A population of 260 individuals (130 females and 130 males) aged 20-30 (mean age of 24.5) was studied by using the Polish version of the chronic self-destructiveness scale and INTE, i.e., the Polish version of the assessing emotions scale. Indirect self-destructiveness has significant correlations with all variables of INTE (overall score, factor I, factor II), and these correlations are negative. The intensity of indirect self-destructiveness differentiates significantly the height of the emotional intelligence and vice versa: the height of the emotional intelligence differentiates significantly the intensity of indirect self-destructiveness. Indirect self-destructiveness has negative correlations with emotional intelligence as well as its components: the ability to recognize emotions and the ability to utilize emotions. The height of emotional intelligence differentiates the intensity of indirect self-destructiveness, and vice versa: the intensity of indirect self-destructiveness differentiates the height of emotional intelligence. It seems advisable to use emotional intelligence in the prophylactic and therapeutic work with persons with various types of disorders, especially with the syndrome of indirect self-destructiveness.

Oxygen Levels Regulate the Development of Human Cortical Radial Glia Cells.

PubMed

Ortega, J Alberto; Sirois, Carissa L; Memi, Fani; Glidden, Nicole; Zecevic, Nada

2017-07-01

The oxygen (O2) concentration is a vital parameter for controlling the survival, proliferation, and differentiation of neural stem cells. A prenatal reduction of O2 levels (hypoxia) often leads to cognitive and behavioral defects, attributable to altered neural development. In this study, we analyzed the effects of O2 levels on human cortical progenitors, the radial glia cells (RGCs), during active neurogenesis, corresponding to the second trimester of gestation. Small changes in O2 levels profoundly affected RGC survival, proliferation, and differentiation. Physiological hypoxia (3% O2) promoted neurogenesis, whereas anoxia (<1% O2) and severe hypoxia (1% O2) arrested the differentiation of human RGCs, mainly by altering the generation of glutamatergic neurons. The in vitro activation of Wnt-β-catenin signaling rescued the proliferation and neuronal differentiation of RGCs subjected to anoxia. Pathologic hypoxia (≤1% O2) also exerted negative effects on gliogenesis, by decreasing the number of O4+ preoligodendrocytes and increasing the number of reactive astrocytes derived from cortical RGCs. O2-dependent alterations in glutamatergic neurogenesis and oligodendrogenesis can lead to significant changes in cortical circuitry formation. A better understanding of the cellular effects caused by changes in O2 levels during human cortical development is essential to elucidating the etiology of numerous neurodevelopmental disorders. Published by Oxford University Press 2016.

Global MicroRNA Profiling in Human Bone Marrow Skeletal-Stromal or Mesenchymal-Stem Cells Identified Candidates for Bone Regeneration.

PubMed

Chang, Chi-Chih; Venø, Morten T; Chen, Li; Ditzel, Nicholas; Le, Dang Q S; Dillschneider, Philipp; Kassem, Moustapha; Kjems, Jørgen

2018-02-07

Bone remodeling and regeneration are highly regulated multistep processes involving posttranscriptional regulation by microRNAs (miRNAs). Here, we performed a global profiling of differentially expressed miRNAs in bone-marrow-derived skeletal cells (BMSCs; also known as stromal or mesenchymal stem cells) during in vitro osteoblast differentiation. We functionally validated the regulatory effects of several miRNAs on osteoblast differentiation and identified 15 miRNAs, most significantly miR-222 and miR-423, as regulators of osteoblastogenesis. In addition, we tested the possible targeting of miRNAs for enhancing bone tissue regeneration. Scaffolds functionalized with miRNA nano-carriers enhanced osteoblastogenesis in 3D culture and retained this ability at least 2 weeks after storage. Additionally, anti-miR-222 enhanced in vivo ectopic bone formation through targeting the cell-cycle inhibitor CDKN1B (cyclin-dependent kinase inhibitor 1B). A number of additional miRNAs exerted additive osteoinductive effects on BMSC differentiation, suggesting that pools of miRNAs delivered locally from an implanted scaffold can provide a promising approach for enhanced bone regeneration. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2009-02-01

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

Granulocyte-macrophage and macrophage colony-stimulating factors differentially regulate alpha v integrin expression on cultured human macrophages.

PubMed

De Nichilo, M O; Burns, G F

1993-03-15

The colony-stimulating factors (CSFs) greatly influence mature macrophage function in vitro: macrophage (M)-CSF induces maturation of monocytes and enhances differentiated cell function; granulocyte-macrophage (GM)-CSF stimulates a variety of antimicrobial functions. In vivo M-CSF is thought to promote differentiation, and GM-CSF is thought to potentiate the inflammatory response. One mechanism by which these differential effects may be achieved is through the receptor-mediated interaction of macrophages with their extracellular matrix. Here we show that M-CSF induces specifically the expression of the alpha v beta 5 integrin receptor, whereas GM-CSF rapidly induces mRNA and surface expression of the alpha v beta 3 integrin. The M-CSF-treated cells acquire a flattened epitheloid phenotype, and on vitronectin the alpha v beta 5 is located in adhesion plaques. These cells do not bind collagen or laminin. In contrast, cells treated with GM-CSF adopt an elongated phenotype on a number of substrates, including collagen and laminin, and express alpha v beta 3 at the leading edge of cells on vitronectin. These results suggest that a primary means by which the CSFs exert their individual effects on mature cells may be through regulating integrin expression.

A Synthesis of Experimental Data Describing the Partitioning of Moderately Volatile Elements in Major Rock Forming Minerals: Implications for the Moon

NASA Technical Reports Server (NTRS)

Vander Kaaden, Kathleen E.; Draper, David S.; McCubbin, Francis M.; Neal, Clive R.; Taylor, G. Jeffrey

2017-01-01

Highly volatile elements [condensation temperatures below about 700 K] and water are highly informative about lunar bulk composition (hence origin), differentiation and magmatic evolution, and the role of impacts in delivering volatiles to the Moon. Fractionation of volatile elements compared to moderately volatile and refractory elements are informative about high-temperature conditions that operated in the proto-lunar disk. Existing data show clearly that the Moon is depleted in volatile elements compared to the bulk silicate Earth. For example, K/Th is 400-700 in the Moon compared to 2800-3000 in Earth. A complicating factor is that the abundances of the highly volatile elements in major lunar lithologies vary by approximately two orders of magnitude. Perhaps most interesting, H2O is not correlated with the concentration of volatile elements, indicating a decoupling of highly volatile elements from the even more volatile H2O. We contend that this decoupling could be a significant tracer of processes operating during lunar formation, differentiation, and bombardment, and the combination of analyzing both volatile elements and water is likely to provide significant insight into lunar geochemical history. This variation and lack of correlation raises the question: what were the relative contributions of crystallization in the magma ocean, subsequent mantle overturn, production of secondary magmas, and addition of volatiles by large impacts in producing this apparently large range in volatile abundances? This current study will produce new partitioning data relevant to the role and distribution of the volatile and non-volatile, yet geochemically significant elements (Co, Ni, Zn, Se, Rb, Sr, Mo, Ag, Cd, In, Sb, Ce, Yb, Tl, Pb, Bi) during the thermal and magmatic evolution of the Moon.

USSR and Eastern Europe Scientific Abstracts, Geophysics, Astronomy and Space, Number 392.

DTIC Science & Technology

1977-03-15

evaluation of the parameters of the observed field. It is proposed that for models formed from a set of elements as described that the problem of...the differential energy spectra for protons during the time of large flares on the sun. [303] IMPROVEMENT OF AES ORBITAL ELEMENTS Moscow...Leningrad, ULUSHSHENIYE ORBITAL’NYKH ELEMENTOV ISZ (Improvement in the Orbital Elements of an Artificial Earth Satellite), Leningrad Forestry Academy

An Autonomous BMP2 Regulatory Element in Mesenchymal Cells

PubMed Central

Kruithof, Boudewijn P.T.; Fritz, David T.; Liu, Yijun; Garsetti, Diane E.; Frank, David B.; Pregizer, Steven K.; Gaussin, Vinciane; Mortlock, Douglas P.; Rogers, Melissa B.

2014-01-01

BMP2 is a morphogen that controls mesenchymal cell differentiation and behavior. For example, BMP2 concentration controls the differentiation of mesenchymal precursors into myocytes, adipocytes, chondrocytes, and osteoblasts. Sequences within the 3′untranslated region (UTR) of the Bmp2 mRNA mediate a post-transcriptional block of protein synthesis. Interaction of cell and developmental stage-specific trans-regulatory factors with the 3′UTR is a nimble and versatile mechanism for modulating this potent morphogen in different cell types. We show here, that an ultra-conserved sequence in the 3′UTR functions independently of promoter, coding region, and 3′UTR context in primary and immortalized tissue culture cells and in transgenic mice. Our findings indicate that the ultra-conserved sequence is an autonomously functioning post-transcriptional element that may be used to modulate the level of BMP2 and other proteins while retaining tissue specific regulatory elements. PMID:21268088

A Singular Differential Equation Stemming from an Optimal Control Problem in Financial Economics

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

Brunovsky, Pavol, E-mail: brunovsky@fmph.uniba.sk; Cerny, Ales, E-mail: ales.cerny.1@city.ac.uk; Winkler, Michael, E-mail: michael.winkler@uni-due.de

2013-10-15

We consider the ordinary differential equation x{sup 2} u'' = axu'+bu-c(u'-1){sup 2}, x Element-Of (0,x{sub 0}), with a Element-Of R, b Element-Of R , c>0 and the singular initial condition u(0)=0, which in financial economics describes optimal disposal of an asset in a market with liquidity effects. It is shown in the paper that if a+b<0 then no continuous solutions exist, whereas if a+b>0 then there are infinitely many continuous solutions with indistinguishable asymptotics near 0. Moreover, it is proved that in the latter case there is precisely one solution u corresponding to the choice x{sub 0}={infinity} which is suchmore » that 0{<=}u(x){<=}x for all x>0, and that this solution is strictly increasing and concave.« less

Screening Test Items for Differential Item Functioning

ERIC Educational Resources Information Center

Longford, Nicholas T.

2014-01-01

A method for medical screening is adapted to differential item functioning (DIF). Its essential elements are explicit declarations of the level of DIF that is acceptable and of the loss function that quantifies the consequences of the two kinds of inappropriate classification of an item. Instead of a single level and a single function, sets of…

Avenues of Influence: Cross-Cultural Implications

DTIC Science & Technology

2014-04-01

focused on comparisons between individualistic and collectivistic cultures . Furthermore, given the differential emphasis toward group factors in...either individualistic or collectivistic cultures , social influence tactics involving group social elements may be a good starting point for exploring...in Two Cultures : The Differential Influence of Social Proof and Commitment/Consistency on collectivists and Individualists . Personality and Social

Opinion: Building epithelial architecture: insights from three-dimensional culture models.

PubMed

O'Brien, Lucy Erin; Zegers, Mirjam M P; Mostov, Keith E

2002-07-01

How do individual cells organize into multicellular tissues? Here, we propose that the morphogenetic behaviour of epithelial cells is guided by two distinct elements: an intrinsic differentiation programme that drives formation of a lumen-enclosing monolayer, and a growth factor-induced, transient de-differentiation that allows this monolayer to be remodelled.

Hybrid finite element method for describing the electrical response of biological cells to applied fields.

PubMed

Ying, Wenjun; Henriquez, Craig S

2007-04-01

A novel hybrid finite element method (FEM) for modeling the response of passive and active biological membranes to external stimuli is presented. The method is based on the differential equations that describe the conservation of electric flux and membrane currents. By introducing the electric flux through the cell membrane as an additional variable, the algorithm decouples the linear partial differential equation part from the nonlinear ordinary differential equation part that defines the membrane dynamics of interest. This conveniently results in two subproblems: a linear interface problem and a nonlinear initial value problem. The linear interface problem is solved with a hybrid FEM. The initial value problem is integrated by a standard ordinary differential equation solver such as the Euler and Runge-Kutta methods. During time integration, these two subproblems are solved alternatively. The algorithm can be used to model the interaction of stimuli with multiple cells of almost arbitrary geometries and complex ion-channel gating at the plasma membrane. Numerical experiments are presented demonstrating the uses of the method for modeling field stimulation and action potential propagation.

Identification of a TAAT-containing motif required for high level expression of the COL1A1 promoter in differentiated osteoblasts of transgenic mice

NASA Technical Reports Server (NTRS)

Dodig, M.; Kronenberg, M. S.; Bedalov, A.; Kream, B. E.; Gronowicz, G.; Clark, S. H.; Mack, K.; Liu, Y. H.; Maxon, R.; Pan, Z. Z.;

Pluripotent and Multipotent Stem Cells Display Distinct Hypoxic miRNA Expression Profiles

PubMed Central

Agrawal, Rahul; Dale, Tina P.; Al-Zubaidi, Mohammed A.; Benny Malgulwar, Prit; Forsyth, Nicholas R.; Kulshreshtha, Ritu

2016-01-01

MicroRNAs are reported to have a crucial role in the regulation of self-renewal and differentiation of stem cells. Hypoxia has been identified as a key biophysical element of the stem cell culture milieu however, the link between hypoxia and miRNA expression in stem cells remains poorly understood. We therefore explored miRNA expression in hypoxic human embryonic and mesenchymal stem cells (hESCs and hMSCs). A total of 50 and 76 miRNAs were differentially regulated by hypoxia (2% O2) in hESCs and hMSCs, respectively, with a negligible overlap of only three miRNAs. We found coordinate regulation of precursor and mature miRNAs under hypoxia suggesting their regulation mainly at transcriptional level. Hypoxia response elements were located upstream of 97% of upregulated hypoxia regulated miRNAs (HRMs) suggesting hypoxia-inducible-factor (HIF) driven transcription. HIF binding to the candidate cis-elements of specific miRNAs under hypoxia was confirmed by Chromatin immunoprecipitation coupled with qPCR. Role analysis of a subset of upregulated HRMs identified linkage to reported inhibition of differentiation while a downregulated subset of HRMs had a putative role in the promotion of differentiation. MiRNA-target prediction correlation with published hypoxic hESC and hMSC gene expression profiles revealed HRM target genes enriched in the cytokine:cytokine receptor, HIF signalling and pathways in cancer. Overall, our study reveals, novel and distinct hypoxia-driven miRNA signatures in hESCs and hMSCs with the potential for application in optimised culture and differentiation models for both therapeutic application and improved understanding of stem cell biology. PMID:27783707

Tissue engineering bioreactor systems for applying physical and electrical stimulations to cells.

PubMed

Jin, GyuHyun; Yang, Gi-Hoon; Kim, GeunHyung

2015-05-01

Bioreactor systems in tissue engineering applications provide various types of stimulation to mimic the tissues in vitro and in vivo. Various bioreactors have been designed to induce high cellular activities, including initial cell attachment, cell growth, and differentiation. Although cell-stimulation processes exert mostly positive effects on cellular responses, in some cases such stimulation can also have a negative effect on cultured cells. In this review, we discuss various types of bioreactor and the positive and negative effects of stimulation (physical, chemical, and electrical) on various cultured cell types. © 2014 Wiley Periodicals, Inc.

Differential high pressure survival in stationary-phase Escherichia coli MG1655

NASA Astrophysics Data System (ADS)

Griffin, Patrick L.; Kish, Adrienne; Steele, Andrew; Hemley, Russell J.

2011-06-01

Hydrostatic pressure exerts a profound influence on nearly all facets of cellular structure and function with exposures to sufficiently high pressure leading to microbial inactivation. We report the first observation of a persistent, pressure-resistant subpopulation within stationary-phase samples of Escherichia coli MG1655, a mesophilic bacterium adapted to surface pressure. This high pressure-resistant subpopulation exhibits pressure survival ranging from 0.6 to 2.0 orders of magnitude greater survival than high pressure treatments at pressures of 225-400 MPa. We also examine some aspects of pressure treatment protocol that may influence the measurements of high pressure survival.

Density-Dependent Conformable Space-time Fractional Diffusion-Reaction Equation and Its Exact Solutions

NASA Astrophysics Data System (ADS)

Hosseini, Kamyar; Mayeli, Peyman; Bekir, Ahmet; Guner, Ozkan

2018-01-01

In this article, a special type of fractional differential equations (FDEs) named the density-dependent conformable fractional diffusion-reaction (DDCFDR) equation is studied. Aforementioned equation has a significant role in the modelling of some phenomena arising in the applied science. The well-organized methods, including the \\exp (-φ (\\varepsilon )) -expansion and modified Kudryashov methods are exerted to generate the exact solutions of this equation such that some of the solutions are new and have been reported for the first time. Results illustrate that both methods have a great performance in handling the DDCFDR equation.

Compartmentalized storage tank for electrochemical cell system

NASA Technical Reports Server (NTRS)

Piecuch, Benjamin Michael (Inventor); Dalton, Luke Thomas (Inventor)

2010-01-01

A compartmentalized storage tank is disclosed. The compartmentalized storage tank includes a housing, a first fluid storage section disposed within the housing, a second fluid storage section disposed within the housing, the first and second fluid storage sections being separated by a movable divider, and a constant force spring. The constant force spring is disposed between the housing and the movable divider to exert a constant force on the movable divider to cause a pressure P1 in the first fluid storage section to be greater than a pressure P2 in the second fluid storage section, thereby defining a pressure differential.

On the Stiffness of the Mesh and Urethral Mobility: A Finite Element Analysis.

PubMed

Brandão, Sofia; Parente, Marco; Da Roza, Thuane Huyer; Silva, Elisabete; Ramos, Isabel Maria; Mascarenhas, Teresa; Natal Jorge, Renato Manuel

2017-08-01

Midurethral slings are used to correct urethral hypermobility in female stress urinary incontinence (SUI), defined as the complaint of involuntary urine leakage when the intra-abdominal pressure (IAP) is increased. Structural and thermal features influence their mechanical properties, which may explain postoperative complications, e.g., erosion and urethral obstruction. We studied the effect of the mesh stiffness on urethral mobility at Valsalva maneuver, under impairment of the supporting structures (levator ani and/or ligaments), by using a numerical model. For that purpose, we modeled a sling with "lower" versus "higher" stiffness and evaluated the mobility of the bladder and urethra, that of the urethrovesical junction (the α-angle), and the force exerted at the fixation of the sling. The effect of impaired levator ani or pubourethral ligaments (PUL) alone on the organs displacement and α-angle opening was similar, showing their important role together on urethral stabilization. When the levator ani and all the ligaments were simulated as impaired, the descent of the bladder and urethra went up to 25.02 mm, that of the bladder neck was 14.57 mm, and the α-angle was 129.7 deg, in the range of what was found in women with SUI. Both meshes allowed returning to normal positioning, although at the cost of higher force exerted by the mesh with higher stiffness (3.4 N against 2.3 N), which can relate to tissue erosion. This finite element analysis allowed mimicking the biomechanical response of the pelvic structures in response to changing a material property of the midurethral synthetic mesh.

Modules and methods for all photonic computing

DOEpatents

Schultz, David R.; Ma, Chao Hung

2001-01-01

A method for all photonic computing, comprising the steps of: encoding a first optical/electro-optical element with a two dimensional mathematical function representing input data; illuminating the first optical/electro-optical element with a collimated beam of light; illuminating a second optical/electro-optical element with light from the first optical/electro-optical element, the second optical/electro-optical element having a characteristic response corresponding to an iterative algorithm useful for solving a partial differential equation; iteratively recirculating the signal through the second optical/electro-optical element with light from the second optical/electro-optical element for a predetermined number of iterations; and, after the predetermined number of iterations, optically and/or electro-optically collecting output data representing an iterative optical solution from the second optical/electro-optical element.

Public health benefits of strategies to reduce greenhouse-gas emissions: health implications of short-lived greenhouse pollutants.

PubMed

Smith, Kirk R; Jerrett, Michael; Anderson, H Ross; Burnett, Richard T; Stone, Vicki; Derwent, Richard; Atkinson, Richard W; Cohen, Aaron; Shonkoff, Seth B; Krewski, Daniel; Pope, C Arden; Thun, Michael J; Thurston, George

2009-12-19

In this report we review the health effects of three short-lived greenhouse pollutants-black carbon, ozone, and sulphates. We undertook new meta-analyses of existing time-series studies and an analysis of a cohort of 352,000 people in 66 US cities during 18 years of follow-up. This cohort study provides estimates of mortality effects from long-term exposure to elemental carbon, an indicator of black carbon mass, and evidence that ozone exerts an independent risk of mortality. Associations among these pollutants make drawing conclusions about their individual health effects difficult at present, but sulphate seems to have the most robust effects in multiple-pollutant models. Generally, the toxicology of the pure compounds and their epidemiology diverge because atmospheric black carbon, ozone, and sulphate are associated and could interact with related toxic species. Although sulphate is a cooling agent, black carbon and ozone could together exert nearly half as much global warming as carbon dioxide. The complexity of these health and climate effects needs to be recognised in mitigation policies. Copyright 2009 Elsevier Ltd. All rights reserved.

Public health benefits of strategies to reduce greenhouse-gas emissions: health implications of short-lived greenhouse pollutants

PubMed Central

Smith, Kirk R.; Jerrett, Michael; Anderson, H Ross; Burnett, Richard T.; Stone, Vicki; Derwent, Richard; Atkinson, Richard W.; Cohen, Aaron; Shonkoff, Seth B.; Krewski, Daniel; Pope, C. Arden; Thun, Michael J.; Thurston, George

2014-01-01

In this report we review the health effects of three short-lived greenhouse pollutants—black carbon, ozone, and sulphates. We undertook new meta-analyses of existing time-series studies and an analysis of a cohort of 352 000 people in 66 US cities during 18 years of follow-up. This cohort study provides estimates of mortality effects from long-term exposure to elemental carbon, an indicator of black carbon mass, and evidence that ozone exerts an independent risk of mortality. Associations among these pollutants make drawing conclusions about their individual health effects difficult at present, but sulphate seems to have the most robust effects in multiple-pollutant models. Generally, the toxicology of the pure compounds and their epidemiology diverge because atmospheric black carbon, ozone, and sulphate are associated and could interact with related toxic species. Although sulphate is a cooling agent, black carbon and ozone could together exert nearly half as much global warming as carbon dioxide. The complexity of these health and climate effects needs to be recognised in mitigation policies. PMID:19942276

Differential diagnosis of hyperkalemia: an update to a complex problem.

PubMed

Eleftheriadis, T; Leivaditis, K; Antoniadi, G; Liakopoulos, V

2012-10-01

Hyperkalemia is a relative common and sometimes life threatening electorlyte disorder. Although its symptomatic treatment is relatively easy, since precise therapeutic algorithms are available, its differential diagnosis is more complicated. The present review aims to unfold the differential diagnosis of hypekalemia using a pathophysiological, albeit clinically useful, approach. The basic elements of potassium homeostasis are provided, the causes of hyperkalemia are categorized and analysed and finally the required for the diferrential diagnosis laboratory tests are mentioned.

Nuclear matrix protein SMAR1 control regulatory T-cell fate during inflammatory bowel disease (IBD)

PubMed Central

Mirlekar, B; Ghorai, S; Khetmalas, M; Bopanna, R; Chattopadhyay, S

2015-01-01

Regulatory T (Treg) cells are essential for self-tolerance and immune homeostasis. Transcription factor Foxp3, a positive regulator of Treg cell differentiation, has been studied to some extent. Signal transducer and activator of transcription factor 3 (STAT3) is known to negatively regulate Foxp3. It is not clear how STAT3 is regulated during Treg differentiation. We show that SMAR1, a known transcription factor and tumor suppressor, is directly involved in maintaining Treg cell fate decision. T-cell-specific conditional knockdown of SMAR1 exhibits increased susceptibility towards inflammatory disorders, such as colitis. The suppressive function of Treg cells is compromised in the absence of SMAR1 leading to increased T helper type 17 (Th17) differentiation and inflammation. Compared with wild-type, the SMAR1−/− Treg cells showed increased susceptibility of inflammatory bowel disease in Rag1−/− mice, indicating the role of SMAR1 in compromising Treg cell differentiation resulting in severe colitis. We show that SMAR1 negatively regulate STAT3 expression favoring Foxp3 expression and Treg cell differentiation. SMAR1 binds to the MAR element of STAT3 promoter, present adjacent to interleukin-6 response elements. Thus Foxp3, a major driver of Treg cell differentiation, is regulated by SMAR1 via STAT3 and a fine-tune balance between Treg and Th17 phenotype is maintained. PMID:25993445

A Circuit to Demonstrate Phase Relationships in "RLC" Circuits

ERIC Educational Resources Information Center

Sokol, P. E.; Warren, G.; Zheng, B.; Smith, P.

2013-01-01

We have developed a circuit to demonstrate the phase relationships between resistive and reactive elements in series "RLC" circuits. We utilize a differential amplifier to allow the phases of the three elements and the current to be simultaneously displayed on an inexpensive four channel oscilloscope. We have included a novel circuit…

CaMKII Signaling Stimulates Mef2c Activity In Vitro but Only Minimally Affects Murine Long Bone Development in vivo

PubMed Central

Amara, Chandra S.; Fabritius, Christine; Houben, Astrid; Wolff, Lena I.; Hartmann, Christine

2017-01-01

The long bones of vertebrate limbs form by endochondral ossification, whereby mesenchymal cells differentiate into chondrogenic progenitors, which then differentiate into chondrocytes. Chondrocytes undergo further differentiation from proliferating to prehypertrophic, and finally to hypertrophic chondrocytes. Several signaling pathways and transcription factors regulate this process. Previously, we and others have shown in chicken that overexpression of an activated form of Calcium/calmodulin-dependent kinase II (CaMKII) results in ectopic chondrocyte maturation. Here, we show that this is not the case in the mouse. Although, in vitro Mef2c activity was upregulated by about 55-fold in response to expression of an activated form of CaMKII (DACaMKII), transgenic mice that expressed a dominant-active form of CaMKII under the control of the Col2a1 regulatory elements display only a very transient and mild phenotype. Here, only the onset of chondrocyte hypertrophy at E12.5 is accelerated. It is also this early step in chondrocyte differentiation that is temporarily delayed around E13.5 in transgenic mice expressing the peptide inhibitor CaM-KIIN from rat (rKIIN) under the control of the Col2a1 regulatory elements. Yet, ultimately DACaMKII, as well as rKIIN transgenic mice are born with completely normal skeletal elements with regard to their length and growth plate organization. Hence, our in vivo analysis suggests that CaMKII signaling plays a minor role in chondrocyte maturation in mice. PMID:28361052

Modelling the petrogenesis of high Rb/Sr silicic magmas

USGS Publications Warehouse

Halliday, A.N.; Davidson, J.P.; Hildreth, W.; Holden, P.

1991-01-01

Rhyolites can be highly evolved with Sr contents as low as 0.1 ppm and Rb Sr > 2,000. In contrast, granite batholiths are commonly comprised of rocks with Rb Sr 100. Mass-balance modelling of source compositions, differentiation and contamination using the trace-element geochemistry of granites are therefore commonly in error because of the failure to account for evolved differentiates that may have been erupted from the system. Rhyolitic magmas with very low Sr concentrations (???1 ppm) cannot be explained by any partial melting models involving typical crustal source compositions. The only plausible mechanism for the production of such rhyolites is Rayleigh fractional crystallization involving substantial volumes of cumulates. A variety of methods for modelling the differentiation of magmas with extremely high Rb/Sr is discussed. In each case it is concluded that the bulk partition coefficients for Sr have to be large. In the simplest models, the bulk DSr of the most evolved types is modelled as > 50. Evidence from phenocryst/glass/whole-rock concentrations supports high Sr partition coefficients in feldspars from high silica rhyolites. However, the low modal abundance of plagioclase commonly observed in such rocks is difficult to reconcile with such simple fractionation models of the observed trace-element trends. In certain cases, this may be because the apparent trace-element trend defined by the suite of cognetic rhyolites is the product of different batches of magma with separate differentiation histories accumulating in the magma chamber roof zone. ?? 1991.

Symbolic computation of equivalence transformations and parameter reduction for nonlinear physical models

NASA Astrophysics Data System (ADS)

Cheviakov, Alexei F.

2017-11-01

An efficient systematic procedure is provided for symbolic computation of Lie groups of equivalence transformations and generalized equivalence transformations of systems of differential equations that contain arbitrary elements (arbitrary functions and/or arbitrary constant parameters), using the software package GeM for Maple. Application of equivalence transformations to the reduction of the number of arbitrary elements in a given system of equations is discussed, and several examples are considered. The first computational example of generalized equivalence transformations where the transformation of the dependent variable involves an arbitrary constitutive function is presented. As a detailed physical example, a three-parameter family of nonlinear wave equations describing finite anti-plane shear displacements of an incompressible hyperelastic fiber-reinforced medium is considered. Equivalence transformations are computed and employed to radically simplify the model for an arbitrary fiber direction, invertibly reducing the model to a simple form that corresponds to a special fiber direction, and involves no arbitrary elements. The presented computation algorithm is applicable to wide classes of systems of differential equations containing arbitrary elements.

Rapamycin and CHIR99021 Coordinate Robust Cardiomyocyte Differentiation From Human Pluripotent Stem Cells Via Reducing p53-Dependent Apoptosis.

PubMed

Qiu, Xiao-Xu; Liu, Yang; Zhang, Yi-Fan; Guan, Ya-Na; Jia, Qian-Qian; Wang, Chen; Liang, He; Li, Yong-Qin; Yang, Huang-Tian; Qin, Yong-Wen; Huang, Shuang; Zhao, Xian-Xian; Jing, Qing

2017-10-02

Cardiomyocytes differentiated from human pluripotent stem cells can serve as an unexhausted source for a cellular cardiac disease model. Although small molecule-mediated cardiomyocyte differentiation methods have been established, the differentiation efficiency is relatively unsatisfactory in multiple lines due to line-to-line variation. Additionally, hurdles including line-specific low expression of endogenous growth factors and the high apoptotic tendency of human pluripotent stem cells also need to be overcome to establish robust and efficient cardiomyocyte differentiation. We used the H9-human cardiac troponin T-eGFP reporter cell line to screen for small molecules that promote cardiac differentiation in a monolayer-based and growth factor-free differentiation model. We found that collaterally treating human pluripotent stem cells with rapamycin and CHIR99021 during the initial stage was essential for efficient and reliable cardiomyocyte differentiation. Moreover, this method maintained consistency in efficiency across different human embryonic stem cell and human induced pluripotent stem cell lines without specifically optimizing multiple parameters (the efficiency in H7, H9, and UQ1 human induced pluripotent stem cells is 98.3%, 93.3%, and 90.6%, respectively). This combination also increased the yield of cardiomyocytes (1:24) and at the same time reduced medium consumption by about 50% when compared with the previous protocols. Further analysis indicated that inhibition of the mammalian target of rapamycin allows efficient cardiomyocyte differentiation through overcoming p53-dependent apoptosis of human pluripotent stem cells during high-density monolayer culture via blunting p53 translation and mitochondrial reactive oxygen species production. We have demonstrated that mammalian target of rapamycin exerts a stage-specific and multifaceted regulation over cardiac differentiation and provides an optimized approach for generating large numbers of functional cardiomyocytes for disease modeling and in vitro drug screening. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

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

PubMed Central

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

2014-01-01

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

Genes That Bias Mendelian Segregation

PubMed Central

Grognet, Pierre; Lalucque, Hervé; Malagnac, Fabienne; Silar, Philippe

2014-01-01

Mendel laws of inheritance can be cheated by Meiotic Drive Elements (MDs), complex nuclear genetic loci found in various eukaryotic genomes and distorting segregation in their favor. Here, we identify and characterize in the model fungus Podospora anserina Spok1 and Spok2, two MDs known as Spore Killers. We show that they are related genes with both spore-killing distorter and spore-protecting responder activities carried out by the same allele. These alleles act as autonomous elements, exert their effects independently of their location in the genome and can act as MDs in other fungi. Additionally, Spok1 acts as a resistance factor to Spok2 killing. Genetical data and cytological analysis of Spok1 and Spok2 localization during the killing process suggest a complex mode of action for Spok proteins. Spok1 and Spok2 belong to a multigene family prevalent in the genomes of many ascomycetes. As they have no obvious cellular role, Spok1 and Spok2 Spore Killer genes represent a novel kind of selfish genetic elements prevalent in fungal genome that proliferate through meiotic distortion. PMID:24830502

Genes that bias Mendelian segregation.

PubMed

Grognet, Pierre; Lalucque, Hervé; Malagnac, Fabienne; Silar, Philippe

2014-01-01

Mendel laws of inheritance can be cheated by Meiotic Drive Elements (MDs), complex nuclear genetic loci found in various eukaryotic genomes and distorting segregation in their favor. Here, we identify and characterize in the model fungus Podospora anserina Spok1 and Spok2, two MDs known as Spore Killers. We show that they are related genes with both spore-killing distorter and spore-protecting responder activities carried out by the same allele. These alleles act as autonomous elements, exert their effects independently of their location in the genome and can act as MDs in other fungi. Additionally, Spok1 acts as a resistance factor to Spok2 killing. Genetical data and cytological analysis of Spok1 and Spok2 localization during the killing process suggest a complex mode of action for Spok proteins. Spok1 and Spok2 belong to a multigene family prevalent in the genomes of many ascomycetes. As they have no obvious cellular role, Spok1 and Spok2 Spore Killer genes represent a novel kind of selfish genetic elements prevalent in fungal genome that proliferate through meiotic distortion.

Large-deflection statics analysis of active cardiac catheters through co-rotational modelling.

PubMed

Peng Qi; Chen Qiu; Mehndiratta, Aadarsh; I-Ming Chen; Haoyong Yu

2016-08-01

This paper presents a co-rotational concept for large-deflection formulation of cardiac catheters. Using this approach, the catheter is first discretized with a number of equal length beam elements and nodes, and the rigid body motions of an individual beam element are separated from its deformations. Therefore, it is adequate for modelling arbitrarily large deflections of a catheter with linear elastic analysis at the local element level. A novel design of active cardiac catheter of 9 Fr in diameter at the beginning of the paper is proposed, which is based on the contra-rotating double helix patterns and is improved from the previous prototypes. The modelling section is followed by MATLAB simulations of various deflections when the catheter is exerted different types of loads. This proves the feasibility of the presented modelling approach. To the best knowledge of the authors, it is the first to utilize this methodology for large-deflection static analysis of the catheter, which will enable more accurate control of robot-assisted cardiac catheterization procedures. Future work would include further experimental validations.

Pan-cancer analysis of somatic copy number alterations implicates IRS4 and IGF2 in enhancer hijacking

PubMed Central

Weischenfeldt, Joachim; Dubash, Taronish; Drainas, Alexandros P.; Mardin, Balca R.; Chen, Yuanyuan; Stütz, Adrian M.; Waszak, Sebastian M.; Bosco, Graziella; Halvorsen, Ann Rita; Raeder, Benjamin; Efthymiopoulos, Theocharis; Erkek, Serap; Siegl, Christine; Brenner, Hermann; Brustugun, Odd Terje; Dieter, Sebastian M.; Northcott, Paul A.; Petersen, Iver; Pfister, Stefan M.; Schneider, Martin; Solberg, Steinar K.; Thunissen, Erik; Weichert, Wilko; Zichner, Thomas; Thomas, Roman; Peifer, Martin; Helland, Aslaug; Ball, Claudia R.; Jechlinger, Martin; Sotillo, Rocio; Glimm, Hanno; Korbel, Jan O.

2018-01-01

Extensive prior research has focused on somatic copy-number alterations (SCNAs) affecting cancer genes, yet the extent to which recurrent SCNAs exert their influence through rearranging cis-regulatory elements remains unclear. Here, we present a framework for inferring cancer-related gene overexpression resulting from cis-regulatory element reorganization (e.g., enhancer hijacking), by integrating SCNAs, gene expression data, and information on chromatin interaction domains. Analysis of 7,416 cancer genomes uncovered several pan-cancer candidate genes, including IRS4, SMARCA1 and TERT. We demonstrate that IRS4 overexpression in lung cancer associates with recurrent deletions in cis, and present evidence supporting a tumor-promoting role. We additionally pursued cancer type-specific analyses, uncovering IGF2 as a target for enhancer hijacking in colorectal cancer. IGF2-containing tandem duplications result in the de novo formation of a 3D contact domain comprising IGF2 and a lineage-specific super-enhancer, which mediates high-level gene activation. Our framework enables systematic inference of cis-regulatory element rearrangements mediating dysregulation in cancer. PMID:27869826

A versatile transfection assay system to evaluate the biological effects of diverse industrial chemicals.

PubMed

Koizumi, Shinji; Ohno, Shotaro; Otsuka, Fuminori

2012-01-01

Gene expression processes are now recognized as important targets of the toxic effects exerted by industrial chemicals. The transient transfection assay is a powerful tool to evaluate such effects. Thus, we developed a versatile assay system by constructing a basic reporter plasmid in which the regulatory DNA sequence to be studied can easily be substituted. To verify the performance of this system, reporter plasmids carrying any of the three distinct regulatory sequences, estrogen responsive element (ERE), glucocorticoid responsive element (GRE) and xenobiotic responsive element (XRE) were constructed. After transfection of human cells, these plasmids successfully expressed the relevant reporter genes in response to specific inducers, β-estradiol, dexamethasone and 3-methylcholanthrene, respectively. Several industrial chemicals were assayed using these reporter plasmids, and the ability of p-dimethylaminoazobenzene to elevate GRE- and XRE-mediated transcription was detected. α-Naphthylamine and o-tolidine were also observed to increase the XRE-mediated response. The transfection assay system established here will be useful to evaluate the effects of a wide variety of industrial chemicals.

Space-based measurements of elemental abundances and their relation to solar abundances

NASA Technical Reports Server (NTRS)

Coplan, M. A.; Ogilvie, K. W.; Bochsler, P.; Geiss, J.

1990-01-01

The Ion Composition Instrument (ICI) aboard the ISEE-3/ICE spacecraft was in the solar wind continuously from August 1978 to December 1982. The results made it possible to establish long-term average solar wind abundance values for helium, oxygen, neon, silicon, and iron. The Charge-Energy-Mass instrument aboard the CCE spacecraft of the AMPTE mission has measured the abundance of these elements in the magnetosheath and has also added carbon, nitrogen, magnesium, and sulfur to the list. There is strong evidence that these magnetosheath abundances are representative of the solar wind. Other sources of solar wind abundances are Solar Energetic Particle experiments and Apollo lunar foils. When comparing the abundances from all of these sources with photospheric abundances, it is clear that helium is depleted in the solar wind while silicon and iron are enhanced. Solar wind abundances for carbon, nitrogen, oxygen, and neon correlate well with the photospheric values. The incorporation of minor ions into the solar wind appears to depend upon both the ionization times for the elements and the Coulomb drag exerted by the outflowing proton flux.

Simulation analysis and experimental verification of spiral-tube-type valveless piezoelectric pump with gyroscopic effect

NASA Astrophysics Data System (ADS)

Leng, Xuefei; Zhang, Jianhui; Jiang, Yan; Wang, Shouyin; Zhao, Chunsheng

2014-07-01

The current research of the valveless piezoelectric pump focuses on increasing the flow rate and pressure differential. Compared with the valve piezoelectric pump, the valveless one has excellent performances in simple structure, low cost, and easy miniaturization. So, their important development trend is the mitigation of their weakness, and the multi-function integration. The flow in a spiral tube element is sensitive to the element attitude caused by the Coriolis force, and that a valveless piezoelectric pump is designed by applying this phenomenon. The pump has gyroscopic effect, and has both the actuator function of fluid transfer and the sensor function, which can obtain the angular velocity when its attitude changes. First, the present paper analyzes the flow characteristics in the tube, obtains the calculation formula for the pump flow, and identifies the relationship between pump attitude and flow, which clarifies the impact of flow and driving voltage, frequency, spiral line type and element attitude, and verifies the gyroscopic effect of the pump. Then, the finite element simulation is used to verify the theory. Finally, a pump is fabricated for experimental testing of the relationship between pump attitude and pressure differential. Experimental results show that when Archimedes spiral θ=4π is selected for the tube design, and the rotation speed of the plate is 70 r/min, the pressure differential is 88.2 Pa, which is 1.5 times that of 0 r/min rotation speed. The spiral-tube-type valveless piezoelectric pump proposed can turn the element attitude into a form of pressure output, which is important for the multi-function integration of the valveless piezoelectric pump and for the development of civil gyroscope in the future.

Geochemical evolution of Jurassic diorites from the Bristol Lake region, California, USA, and the role of assimilation

USGS Publications Warehouse

Young, E.D.; Wooden, J.L.; Shieh, Y.-N.; Farber, D.

1992-01-01

Late Jurassic dioritic plutons from the Bristol Lake region of the eastern Mojave Desert share several geochemical attributes with high-alumina basalts, continental hawaiite basalts, and high-K are andesites including: high K2O concentrations; high Al2O3 (16-19 weight %); elevated Zr/TiO2; LREE (light-rare-earth-element) enrichment (La/YbCN=6.3-13.3); and high Nb. Pearce element ratio analysis supported by petrographic relations demonstrates that P, Hf, and Zr were conserved during differentiation. Abundances of conserved elements suggest that dioritic plutons from neighboring ranges were derived from similar parental melts. In the most voluminous suite, correlated variations in elemental concentrations and (87Sr/86Sr)i indicate differentiation by fractional crystallization of hornblende and plagioclase combined with assimilation of a component characterized by abundant radiogenic Sr. Levenberg-Marquardt and Monte Carlo techniques were used to obtain optimal solutions to non-linear inverse models for fractional crystallization-assimilation processes. Results show that the assimilated material was chemically analogous to lower crustal mafic granulites and that the mass ratio of contaminant to parental magma was on the order of 0.1. Lack of enrichment in 18O with differentiation is consistent with the model results. Elemental concentrations and O, Sr, and Nd isotopic data point to a hydrous REE-enriched subcontinental lithospheric source similar to that which produced some Cenozoic continental hawaiites from the southern Cordillera. Isotopic compositions of associated granitoids suggest that partial melting of this subcontinental lithosphere may have been an important process in the development of the Late Jurassic plutonic arc of the eastern Mojave Desert. ?? 1992 Springer-Verlag.

Early demethylation of non-CpG, CpC-rich, elements in the myogenin 5′-flanking region

PubMed Central

Fuso, Andrea; Ferraguti, Giampiero; Grandoni, Francesco; Ruggeri, Raffaella; Scarpa, Sigfrido; Strom, Roberto

2010-01-01

The dynamic changes and structural patterns of DNA methylation of genes without CpG islands are poorly characterized. The relevance of CpG to the non-CpG methylation equilibrium in transcriptional repression is unknown. In this work, we analyzed the DNA methylation pattern of the 5′-flanking of the myogenin gene, a positive regulator of muscle differentiation with no CpG island and low CpG density, in both C2C12 muscle satellite cells and embryonic muscle. Embryonic brain was studied as a non-expressing tissue. High levels of both CpG and non-CpG methylation were observed in non-expressing experimental conditions. Both CpG and non-CpG methylation rapidly dropped during muscle differentiation and myogenin transcriptional activation with active demethylation dynamics. Non-CpG demethylation occurred more rapidly than CpG demethylation. Demethylation spread from initially highly methylated short CpC-rich elements to a virtually unmethylated status. These short elements have a high CpC content and density, share some motifs and largely coincide with putative recognition sequences of some differentiation-related transcription factors. Our findings point to a dynamically controlled equilibrium between CpG and non-CpG active demethylation in the transcriptional control of tissue-specific genes. The short CpC-rich elements are new structural features of the methylation machinery, whose functions may include priming the complete demethylation of a transcriptionally crucial DNA region. PMID:20935518

Recent Amplification of the Kangaroo Endogenous Retrovirus, KERV, Limited to the Centromere▿

PubMed Central

Ferreri, Gianni C.; Brown, Judith D.; Obergfell, Craig; Jue, Nathaniel; Finn, Caitlin E.; O'Neill, Michael J.; O'Neill, Rachel J.

2011-01-01

Mammalian retrotransposons, transposable elements that are processed through an RNA intermediate, are categorized as short interspersed elements (SINEs), long interspersed elements (LINEs), and long terminal repeat (LTR) retroelements, which include endogenous retroviruses. The ability of transposable elements to autonomously amplify led to their initial characterization as selfish or junk DNA; however, it is now known that they may acquire specific cellular functions in a genome and are implicated in host defense mechanisms as well as in genome evolution. Interactions between classes of transposable elements may exert a markedly different and potentially more significant effect on a genome than interactions between members of a single class of transposable elements. We examined the genomic structure and evolution of the kangaroo endogenous retrovirus (KERV) in the marsupial genus Macropus. The complete proviral structure of the kangaroo endogenous retrovirus, phylogenetic relationship among relative retroviruses, and expression of this virus in both Macropus rufogriseus and M. eugenii are presented for the first time. In addition, we show the relative copy number and distribution of the kangaroo endogenous retrovirus in the Macropus genus. Our data indicate that amplification of the kangaroo endogenous retrovirus occurred in a lineage-specific fashion, is restricted to the centromeres, and is not correlated with LINE depletion. Finally, analysis of KERV long terminal repeat sequences using massively parallel sequencing indicates that the recent amplification in M. rufogriseus is likely due to duplications and concerted evolution rather than a high number of independent insertion events. PMID:21389136

On conforming mixed finite element methods for incompressible viscous flow problems

NASA Technical Reports Server (NTRS)

Gunzburger, M. D; Nicolaides, R. A.; Peterson, J. S.

1982-01-01

The application of conforming mixed finite element methods to obtain approximate solutions of linearized Navier-Stokes equations is examined. Attention is given to the convergence rates of various finite element approximations of the pressure and the velocity field. The optimality of the convergence rates are addressed in terms of comparisons of the approximation convergence to a smooth solution in relation to the best approximation available for the finite element space used. Consideration is also devoted to techniques for efficient use of a Gaussian elimination algorithm to obtain a solution to a system of linear algebraic equations derived by finite element discretizations of linear partial differential equations.

Ablative Thermal Response Analysis Using the Finite Element Method

NASA Technical Reports Server (NTRS)

Dec John A.; Braun, Robert D.

2009-01-01

A review of the classic techniques used to solve ablative thermal response problems is presented. The advantages and disadvantages of both the finite element and finite difference methods are described. As a first step in developing a three dimensional finite element based ablative thermal response capability, a one dimensional computer tool has been developed. The finite element method is used to discretize the governing differential equations and Galerkin's method of weighted residuals is used to derive the element equations. A code to code comparison between the current 1-D tool and the 1-D Fully Implicit Ablation and Thermal Response Program (FIAT) has been performed.

Integrated coherent matter wave circuits

DOE PAGES

Ryu, C.; Boshier, M. G.

2015-09-21

An integrated coherent matter wave circuit is a single device, analogous to an integrated optical circuit, in which coherent de Broglie waves are created and then launched into waveguides where they can be switched, divided, recombined, and detected as they propagate. Applications of such circuits include guided atom interferometers, atomtronic circuits, and precisely controlled delivery of atoms. We report experiments demonstrating integrated circuits for guided coherent matter waves. The circuit elements are created with the painted potential technique, a form of time-averaged optical dipole potential in which a rapidly moving, tightly focused laser beam exerts forces on atoms through theirmore » electric polarizability. Moreover, the source of coherent matter waves is a Bose–Einstein condensate (BEC). Finally, we launch BECs into painted waveguides that guide them around bends and form switches, phase coherent beamsplitters, and closed circuits. These are the basic elements that are needed to engineer arbitrarily complex matter wave circuitry.« less

Design Evaluation Using Finite Element Analysis of Cooled Silicon Nitride Plates for a Turbine Blade Application

NASA Technical Reports Server (NTRS)

Abdul-Aziz, Ali; Baaklini, George Y.; Bhatt, Ramakrishna T.

2001-01-01

Two- and three-dimensional finite element analyses were performed on uncoated and thermal barrier coated (TBC) silicon nitride plates with and without internal cooling by air. Steady-state heat-transfer analyses were done to optimize the size and the geometry of the cooling channels to reduce thermal stresses, and to evaluate the thermal environment experienced by the plate during burner rig testing. The limited experimental data available were used to model the thermal profile exerted by the flame on the plate. Thermal stress analyses were performed to assess the stress response due to thermal loading. Contours for the temperature and the representative stresses for the plates were generated and presented for different cooling hole sizes and shapes. Analysis indicates that the TBC experienced higher stresses, and the temperature gradient was much reduced when the plate was internally cooled by air. The advantages and disadvantages of several cooling channel layouts were evaluated.

Modeling tabular icebergs submerged in the ocean

NASA Astrophysics Data System (ADS)

Stern, A. A.; Adcroft, A.; Sergienko, O.; Marques, G.

2017-08-01

Large tabular icebergs calved from Antarctic ice shelves have long lifetimes (due to their large size), during which they drift across large distances, altering ambient ocean circulation, bottom-water formation, sea-ice formation, and biological primary productivity in the icebergs' vicinity. However, despite their importance, the current generation of ocean circulation models usually do not represent large tabular icebergs. In this study, we develop a novel framework to model large tabular icebergs submerged in the ocean. In this framework, tabular icebergs are represented by pressure-exerting Lagrangian elements that drift in the ocean. The elements are held together and interact with each other via bonds. A breaking of these bonds allows the model to emulate calving events (i.e., detachment of a tabular iceberg from an ice shelf) and tabular icebergs breaking up into smaller pieces. Idealized simulations of a calving tabular iceberg, its drift, and its breakup demonstrate capabilities of the developed framework.

Sugar regulation of SUGAR TRANSPORTER PROTEIN 1 (STP1) expression in Arabidopsis thaliana

PubMed Central

Cordoba, Elizabeth; Aceves-Zamudio, Denise Lizeth; Hernández-Bernal, Alma Fabiola; Ramos-Vega, Maricela; León, Patricia

2015-01-01

Sugars regulate the expression of many genes at the transcriptional level. In Arabidopsis thaliana, sugars induce or repress the expression of >1800 genes, including the STP1 (SUGAR TRANSPORTER PROTEIN 1) gene, which encodes an H+/monosaccharide cotransporter. STP1 transcript levels decrease more rapidly after the addition of low concentrations of sugars than the levels of other repressed genes, such as DIN6 (DARK-INDUCED 6). We found that this regulation is exerted at the transcriptional level and is initiated by phosphorylatable sugars. Interestingly, the sugar signal that modulates STP1 expression is transmitted through a HEXOKINASE 1-independent signalling pathway. Finally, analysis of the STP1 5′ regulatory region allowed us to delimit a region of 309bp that contains the cis elements implicated in the glucose regulation of STP1 expression. Putative cis-acting elements involved in this response were identified. PMID:25281700

Marine Natural Product Honaucin A Attenuates Inflammation by Activating the Nrf2-ARE Pathway.

PubMed

Mascuch, Samantha J; Boudreau, Paul D; Carland, Tristan M; Pierce, N Tessa; Olson, Joshua; Hensler, Mary E; Choi, Hyukjae; Campanale, Joseph; Hamdoun, Amro; Nizet, Victor; Gerwick, William H; Gaasterland, Teresa; Gerwick, Lena

2018-03-23

The cyanobacterial marine natural product honaucin A inhibits mammalian innate inflammation in vitro and in vivo. To decipher its mechanism of action, RNA sequencing was used to evaluate differences in gene expression of cultured macrophages following honaucin A treatment. This analysis led to the hypothesis that honaucin A exerts its anti-inflammatory activity through activation of the cytoprotective nuclear erythroid 2-related factor 2 (Nrf2)-antioxidant response element/electrophile response element (ARE/EpRE) signaling pathway. Activation of this pathway by honaucin A in cultured human MCF7 cells was confirmed using an Nrf2 luciferase reporter assay. In vitro alkylation experiments with the natural product and N-acetyl-l-cysteine suggest that honaucin A activates this pathway through covalent interaction with the sulfhydryl residues of the cytosolic repressor protein Keap1. Honaucin A presents a potential therapeutic lead for diseases with an inflammatory component modulated by Nrf2-ARE.

[Simultaneous determination of trace amounts of zinc, cadmium, lead and copper by the method of anodic voltammetry using factor experimental design].

PubMed

Koen, E

1975-01-01

Using the method of factor planning of the experiment, the author studies and demonstrates the influence exerted by the potential and time of electrolysis, and by the concentration of the background and elements on the heights of anodal peaks upon simultaneous determination of zinc, cadmium, lead and copper microconcentrations. On the ground of statistical elaboration of the results, the optimal condition for polarographic determination through anodal voltamperometry are outlined. According to the cyclic voltametry method, the electrod processes reversibility for zinc, cadmium and lead, as well as the incomplete reversibility for copper are established; the number of electrons participating in the electrochemical reaction are found using the method of gas coulometry. The possibility of simultaneous determination of the four elements' ultramicroconcentrations after the method of voltamperometry with enrichment is proved. The standard deviation is in the range 3.02 to 4.9.

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

Ryu, C.; Boshier, M. G.

An integrated coherent matter wave circuit is a single device, analogous to an integrated optical circuit, in which coherent de Broglie waves are created and then launched into waveguides where they can be switched, divided, recombined, and detected as they propagate. Applications of such circuits include guided atom interferometers, atomtronic circuits, and precisely controlled delivery of atoms. We report experiments demonstrating integrated circuits for guided coherent matter waves. The circuit elements are created with the painted potential technique, a form of time-averaged optical dipole potential in which a rapidly moving, tightly focused laser beam exerts forces on atoms through theirmore » electric polarizability. Moreover, the source of coherent matter waves is a Bose–Einstein condensate (BEC). Finally, we launch BECs into painted waveguides that guide them around bends and form switches, phase coherent beamsplitters, and closed circuits. These are the basic elements that are needed to engineer arbitrarily complex matter wave circuitry.« less

A Locus Encoding Variable Defense Systems against Invading DNA Identified in Streptococcus suis

PubMed Central

Okura, Masatoshi; Nozawa, Takashi; Watanabe, Takayasu; Murase, Kazunori; Nakagawa, Ichiro; Takamatsu, Daisuke; Osaki, Makoto; Sekizaki, Tsutomu; Gottschalk, Marcelo; Hamada, Shigeyuki

2017-01-01

Streptococcus suis, an important zoonotic pathogen, is known to have an open pan-genome and to develop a competent state. In S. suis, limited genetic lineages are suggested to be associated with zoonosis. However, little is known about the evolution of diversified lineages and their respective phenotypic or ecological characteristics. In this study, we performed comparative genome analyses of S. suis, with a focus on the competence genes, mobile genetic elements, and genetic elements related to various defense systems against exogenous DNAs (defense elements) that are associated with gene gain/loss/exchange mediated by horizontal DNA movements and their restrictions. Our genome analyses revealed a conserved competence-inducing peptide type (pherotype) of the competence system and large-scale genome rearrangements in certain clusters based on the genome phylogeny of 58 S. suis strains. Moreover, the profiles of the defense elements were similar or identical to each other among the strains belonging to the same genomic clusters. Our findings suggest that these genetic characteristics of each cluster might exert specific effects on the phenotypic or ecological differences between the clusters. We also found certain loci that shift several types of defense elements in S. suis. Of note, one of these loci is a previously unrecognized variable region in bacteria, at which strains of distinct clusters code for different and various defense elements. This locus might represent a novel defense mechanism that has evolved through an arms race between bacteria and invading DNAs, mediated by mobile genetic elements and genetic competence. PMID:28379509

Developmentally arrested structures preceding cerebellar tumors in von Hippel–Lindau disease

PubMed Central

Shively, Sharon B; Falke, Eric A; Li, Jie; Tran, Maxine G B; Thompson, Eli R; Maxwell, Patrick H; Roessler, Erich; Oldfield, Edward H; Lonser, Russell R; Vortmeyer, Alexander O

2011-01-01

There is increasing evidence that suggests that knockout of tumor-suppressor gene function causes developmental arrest and protraction of cellular differentiation. In the peripheral nervous system of patients with the tumor-suppressor gene disorder, von Hippel–Lindau disease, we have demonstrated developmentally arrested structural elements composed of hemangioblast progenitor cells. Some developmentally arrested structural elements progress to a frank tumor, hemangioblastoma. However, in von Hippel–Lindau disease, hemangioblastomas are frequently observed in the cerebellum, suggesting an origin in the central nervous system. We performed a structural and topographic analysis of cerebellar tissues obtained from von Hippel–Lindau disease patients to identify and characterize developmentally arrested structural elements in the central nervous system. We examined the entire cerebella of five tumor-free von Hippel–Lindau disease patients and of three non-von Hippel–Lindau disease controls. In all, 9 cerebellar developmentally arrested structural elements were detected and topographically mapped in 385 blocks of von Hippel–Lindau disease cerebella. No developmentally arrested structural elements were seen in 214 blocks from control cerebella. Developmentally arrested structural elements are composed of poorly differentiated cells that express hypoxia-inducible factor (HIF)2α, but not HIF1α or brachyury, and preferentially involve the molecular layer of the dorsum cerebelli. For the first time, we identify and characterize developmentally arrested structural elements in the central nervous system of von Hippel–Lindau patients. We provide evidence that developmentally arrested structural elements in the cerebellum are composed of developmentally arrested hemangioblast progenitor cells in the molecular layer of the dorsum cerebelli. PMID:21499240

Chemical evidence for differentiation, evaporation and recondensation from silicate clasts in Gujba

NASA Astrophysics Data System (ADS)

Oulton, Jonathan; Humayun, Munir; Fedkin, Alexei; Grossman, Lawrence

2016-03-01

The silicate and metal clasts in CB chondrites have been inferred to form as condensates from an impact-generated vapor plume between a metal-rich body and a silicate body. A detailed study of the condensation of impact-generated vapor plumes showed that the range of CB silicate clast compositions could not be successfully explained without invoking a chemically differentiated target. Here, we report the most comprehensive elemental study yet performed on CB silicates with 32 silicate clasts from nine slices of Gujba analyzed by laser ablation inductively coupled plasma mass spectrometry for 53 elements. Like in other studies of CBs, the silicate clasts are either barred olivine (BO) or cryptocrystalline (CC) in texture. In major elements, the Gujba silicate clasts ranged from chondritic to refractory enriched. Refractory element abundances ranged from 2 to 10 × CI, with notable anomalies in Ba, Ce, Eu, and U abundances. The two most refractory-enriched BO clasts exhibited negative Ce anomalies and were depleted in U relative to Th, characteristic of volatilization residues, while other BO clasts and the CC clasts exhibited positive Ce anomalies with excess U (1-3 × CI), and Ba (1-6 × CI) anomalies indicating re-condensation of ultra-refractory element depleted vapor. The Rare Earth Elements (REE) also exhibit light REE (LREE) enrichment or depletion in several clasts with a range of (La/Sm)CI of 0.9-1.8. This variation in the LREE is essentially impossible to accomplish by processes involving vapor-liquid or vapor-solid exchange of REE, and appears to have been inherited from a differentiated target. The most distinctive evidence for inherited chemical differentiation is observed in highly refractory element (Sc, Zr, Nb, Hf, Ta, Th) systematics. The Gujba clasts exhibit fractionations in Nb/Ta that correlate positively with Zr/Hf and span the range known from lunar and Martian basalts, and exceed the range in Zr/Hf variation known from eucrites. Variations of highly incompatible refractory elements (e.g., Th) against less incompatible elements (e.g., Zr, Sr, Sc) are not chondritic, but exhibit distinctly higher Th abundances requiring a differentiated crust to be admixed with depleted mantle in ratios that are biased to higher crust/mantle ratios than in a chondritic body. The possibility that these variations are due to admixture of refractory inclusion-debris into normal chondritic matter is raised but cannot be definitively tested because existing ;bulk; analyses of CAIs carry artifacts of unrepresentative sampling. The inferences drawn from the compositions of Gujba silicate clasts, here, complement what has been inferred from the compositions of metallic clasts, but provide surprisingly detailed insight into the structure of the target. Evidence that metal and silicate in CB chondrites both formed from impact-generated vapor plumes, taken together with recent work on metallic nodules in E chondrites, and on ordinary chondrites, indicates that chondrule formation occurs by this mechanism quite widely. However, the nature of the impact on the CB body is quite different than the popular conceptions of impact of partially or wholly molten chondritic bodies and the younger (5 Ma) age of CB chondrules is consistent with origin in a disk with more evolved targets and impactors gravitationally perturbed by nascent planets.

Learning and Recognition of Clothing Genres From Full-Body Images.

PubMed

Hidayati, Shintami C; You, Chuang-Wen; Cheng, Wen-Huang; Hua, Kai-Lung

2018-05-01

According to the theory of clothing design, the genres of clothes can be recognized based on a set of visually differentiable style elements, which exhibit salient features of visual appearance and reflect high-level fashion styles for better describing clothing genres. Instead of using less-discriminative low-level features or ambiguous keywords to identify clothing genres, we proposed a novel approach for automatically classifying clothing genres based on the visually differentiable style elements. A set of style elements, that are crucial for recognizing specific visual styles of clothing genres, were identified based on the clothing design theory. In addition, the corresponding salient visual features of each style element were identified and formulated with variables that can be computationally derived with various computer vision algorithms. To evaluate the performance of our algorithm, a dataset containing 3250 full-body shots crawled from popular online stores was built. Recognition results show that our proposed algorithms achieved promising overall precision, recall, and -score of 88.76%, 88.53%, and 88.64% for recognizing upperwear genres, and 88.21%, 88.17%, and 88.19% for recognizing lowerwear genres, respectively. The effectiveness of each style element and its visual features on recognizing clothing genres was demonstrated through a set of experiments involving different sets of style elements or features. In summary, our experimental results demonstrate the effectiveness of the proposed method in clothing genre recognition.

Optimal moving grids for time-dependent partial differential equations

NASA Technical Reports Server (NTRS)

Wathen, A. J.

1989-01-01

Various adaptive moving grid techniques for the numerical solution of time-dependent partial differential equations were proposed. The precise criterion for grid motion varies, but most techniques will attempt to give grids on which the solution of the partial differential equation can be well represented. Moving grids are investigated on which the solutions of the linear heat conduction and viscous Burgers' equation in one space dimension are optimally approximated. Precisely, the results of numerical calculations of optimal moving grids for piecewise linear finite element approximation of partial differential equation solutions in the least squares norm.

Osteoblast gene expression is differentially regulated by TGF-beta isoforms.

PubMed

Fagenholz, P J; Warren, S M; Greenwald, J A; Bouletreau, P J; Spector, J A; Crisera, F E; Longaker, M T

2001-03-01

The transforming growth factor beta (TGF-beta) superfamily encompasses a number of important growth factors including several TGF-beta isoforms, the bone morphogenetic proteins, activins, inhibins, and growth and differentiation factors. TGF-beta 1, -beta 2, and -beta 3 are three closely related isoforms that are widely expressed during skeletal morphogenesis and bone repair. Numerous studies suggest that each isoform has unique in vivo functions; however, the effects of these TGF-beta isoforms on osteoblast gene expression and maturation have never been directly compared. In the current study, we treated undifferentiated neonatal rat calvaria osteoblast-enriched cell cultures with 2.5 ng/ml of each TGF-beta isoform and analyzed gene expression at 0, 3, 6, and 24 hours. We demonstrated unique isoform-specific regulation of endogenous TGF-beta 1 and type I collagen mRNA transcription. To assess the effects of extended TGF-beta treatment on osteoblast maturation, we differentiated osteoblast cultures in the presence of 2.5 ng/ml of each TGF-beta isoform. Analysis of collagen I, alkaline phosphatase, and osteocalcin demonstrated that each TGF-beta isoform uniquely suppressed the transcription of these osteoblast differentiation markers. Interestingly, TGF-beta isoform treatment increased osteopontin expression in primary osteoblasts after 4 and 10 days of differentiation. To our knowledge, these data provide the first direct comparison of the effects of the TGF-beta isoforms on osteoblast gene expression in vitro. Furthermore, these data suggest that TGF-beta isoforms may exert their unique in vivo effects by differentially regulating osteoblast cytokine secretion, extracellular matrix production, and the rate of cellular maturation.

TWEAK in inclusion-body myositis muscle: possible pathogenic role of a cytokine inhibiting myogenesis.

PubMed

Morosetti, Roberta; Gliubizzi, Carla; Sancricca, Cristina; Broccolini, Aldobrando; Gidaro, Teresa; Lucchini, Matteo; Mirabella, Massimiliano

2012-04-01

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor Fn14 exert pleiotropic effects, including regulation of myogenesis. Sporadic inclusion-body myositis (IBM) is the most common muscle disease of the elderly population and leads to severe disability. IBM mesoangioblasts, different from mesoangioblasts in other inflammatory myopathies, display a myogenic differentiation defect. The objective of the present study was to investigate TWEAK-Fn14 expression in IBM and other inflammatory myopathies and explore whether TWEAK modulation affects myogenesis in IBM mesoangioblasts. TWEAK, Fn14, and NF-κB expression was assessed by immunohistochemistry and Western blot in cell samples from both muscle biopsies and primary cultures. Mesoangioblasts isolated from samples of IBM, dermatomyositis, polymyositis, and control muscles were treated with recombinant human TWEAK, Fn14-Fc chimera, and anti-TWEAK antibody. TWEAK-RNA interference was performed in IBM and dermatomyositis mesoangioblasts. TWEAK levels in culture media were determined by enzyme-linked immunosorbent assay. In IBM muscle, we found increased TWEAK-Fn14 expression. Increased levels of TWEAK were found in differentiation medium from IBM mesoangioblasts. Moreover, TWEAK inhibited myogenic differentiation of mesoangioblasts. Consistent with this evidence, TWEAK inhibition by Fn14-Fc chimera or short interfering RNA induced myogenic differentiation of IBM mesoangioblasts. We provide evidence that TWEAK is a negative regulator of human mesoangioblast differentiation. Dysregulation of the TWEAK-Fn14 axis in IBM muscle may induce progressive muscle atrophy and reduce activation and differentiation of muscle precursor cells. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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

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

Liu, Qi; Wan, Qilong; Yang, Rongtao

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

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

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

Liu, Yumei; Zhang, Ziqiang; Lv, Qiongxia

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

Role of diabetes- and obesity-related protein in the regulation of osteoblast differentiation

PubMed Central

Linares, Gabriel R.; Xing, Weirong; Burghardt, Hans; Baumgartner, Bernhard; Chen, Shin-Tai; Ricart, Wifredo; Fernández-Real, José Manuel; Zorzano, Antonio

2011-01-01

Although thyroid hormone (TH) is known to exert important effects on the skeleton, the nuclear factors constituting the TH receptor coactivator complex and the molecular pathways by which TH mediates its effects on target gene expression in osteoblasts remain poorly understood. A recent study demonstrated that the actions of TH on myoblast differentiation are dependent on diabetes- and obesity-related protein (DOR). However, the role of DOR in osteoblast differentiation is unknown. We found DOR expression increased during in vitro differentiation of bone marrow stromal cells into osteoblasts and also in MC3T3-E1 cells treated with TH. However, DOR expression decreased during cellular proliferation. To determine whether DOR acts as a modulator of TH action during osteoblast differentiation, we examined whether overexpression or knockdown of DOR in MC3T3-E1 cells affects the ability of TH to induce osteoblast differentiation by evaluating alkaline phosphatase (ALP) activity. ALP activity was markedly increased in DOR-overexpressing cells treated with TH. In contrast, loss of DOR dramatically reduced TH stimulation of ALP activity in MC3T3-E1 cells and primary calvaria osteoblasts transduced with lentiviral DOR shRNA. Consistent with reduced ALP activity, mRNA levels of osteocalcin, ALP, and Runx2 were decreased significantly in DOR shRNA cells. In addition, a common single nucleotide polymorphism (SNP), DOR1 found on the promoter of human DOR gene, was associated with circulating osteocalcin levels in nondiabetic subjects. Based on these data, we conclude that DOR plays an important role in TH-mediated osteoblast differentiation, and a DOR SNP associates with plasma osteocalcin in men. PMID:21467300

Differential cross sections and polarization observables from CLAS K* photoproduction and the search for new N* states

NASA Astrophysics Data System (ADS)

Anisovich, A. V.; Hicks, K.; Klempt, E.; Nikonov, V. A.; Sarantsev, A.; Tang, W.; Adikaram, D.; Akbar, Z.; Amaryan, M. J.; Anefalos Pereira, S.; Badui, R. A.; Ball, J.; Battaglieri, M.; Batourine, V.; Bedlinskiy, I.; Biselli, A. S.; Briscoe, W. J.; Burkert, V. D.; Carman, D. S.; Celentano, A.; Chandavar, S.; Chetry, T.; Ciullo, G.; Clark, L.; Cole, P. L.; Compton, N.; Contalbrigo, M.; Crede, V.; D'Angelo, A.; Dashyan, N.; De Vita, R.; De Sanctis, E.; Deur, A.; Djalali, C.; Dugger, M.; Dupre, R.; Egiyan, H.; El Alaoui, A.; El Fassi, L.; Eugenio, P.; Fanchini, E.; Fedotov, G.; Filippi, A.; Fleming, J. A.; Gevorgyan, N.; Ghandilyan, Y.; Giovanetti, K. L.; Girod, F. X.; Gleason, C.; Gothe, R. W.; Griffioen, K. A.; Guo, L.; Hanretty, C.; Harrison, N.; Hattawy, M.; Holtrop, M.; Hughes, S. M.; Ilieva, Y.; Ireland, D. G.; Ishkhanov, B. S.; Isupov, E. L.; Jenkins, D.; Jiang, H.; Jo, H. S.; Joosten, S.; Keller, D.; Khachatryan, G.; Khandaker, M.; Kim, W.; Klein, F. J.; Kubarovsky, V.; Lanza, L.; Lenisa, P.; Livingston, K.; MacGregor, I. J. D.; Markov, N.; McKinnon, B.; Meyer, C. A.; Mirazita, M.; Mokeev, V.; Montgomery, R. A.; Movsisyan, A.; Munevar, E.; Munoz Camacho, C.; Murdoch, G.; Nadel-Turonski, P.; Net, L. A.; Ni, A.; Niccolai, S.; Niculescu, I.; Osipenko, M.; Ostrovidov, A. I.; Paolone, M.; Paremuzyan, R.; Park, K.; Pasyuk, E.; Peng, P.; Phelps, W.; Pisano, S.; Pogorelko, O.; Price, J. W.; Prok, Y.; Puckett, A. J. R.; Raue, B. A.; Ripani, M.; Ritchie, B. G.; Rosner, G.; Roy, P.; Sabatié, F.; Schumacher, R. A.; Sharabian, Y. G.; Skorodumina, Iu.; Smith, G. D.; Sokhan, D.; Sparveris, N.; Stankovic, I.; Stepanyan, S.; Strauch, S.; Sytnik, V.; Tian, Ye.; Ungaro, M.; Voskanyan, H.; Voutier, E.; Walford, N. K.; Watts, D. P.; Wood, M. H.; Zachariou, N.; Zhang, J.; Zonta, I.; CLAS Collaboration

2017-08-01

The reaction γp →K*+ Λ was measured using the CLAS detector for photon energies between the threshold and 3.9 GeV at the Thomas Jefferson National Accelerator Facility. For the first time, spin-density matrix elements have been extracted for this reaction. Differential cross sections, spin density matrix elements, and the Λ recoil polarization are compared with theoretical predictions using the BnGa partial wave analysis. The main result is the evidence for significant contributions from N (1895) 1 /2- and N (2100) 1 /2+ to the reaction. Branching ratios for decays into K* Λ for these resonances and further resonances are reported.

Testis cancer: the forgotten poster child.

PubMed

Raghavan, Derek

2014-07-15

In germ cell cancers, the unique reversibility of malignancy and the balance between somatic differentiation and dedifferentiation may be critical to late relapse that is dominated by non-germ cell elements. Targeting regulators of differentiation may provide a solution, and this may be elucidated via serial liquid biopsies (via circulating tumor cells). ©2014 American Association for Cancer Research.

Differential Item Functioning Analysis of High-Stakes Test in Terms of Gender: A Rasch Model Approach

ERIC Educational Resources Information Center

Alavi, Seyed Mohammad; Bordbar, Soodeh

2017-01-01

Differential Item Functioning (DIF) analysis is a key element in evaluating educational test fairness and validity. One of the frequently cited sources of construct-irrelevant variance is gender which has an important role in the university entrance exam; therefore, it causes bias and consequently undermines test validity. The present study aims…

Making Differentiation a Habit: How to Ensure Success in Academically Diverse Classrooms

ERIC Educational Resources Information Center

Heacox, Diane

2009-01-01

If you're a teacher with an academically diverse classroom (and what classrooms aren't today?), you need this resource. Framed around the critical elements for success in today's classrooms, "Making Differentiation a Habit" gives educators specific, user-friendly tools to optimize teaching, learning, and assessment. Following on the heels of Diane…

The Army Communications Objectives Measurement System (ACOMS) Users’ Manual

DTIC Science & Technology

1988-07-01

UNLIMITED E2 SAME AS P PT. 0 DTIC USERS U n1e las s i f i e ( 22a. NAME OF RESPONSIBLE INDIVIDUAL 22b. TELEPHONE (include Area Code) 22c, OFFICE SYMBOL T...of advertising to be directed at each segment. ACOMS was designed so that the data would be useful in examining brand differentiation , for example...comparison of image elements--at several levels: differentiation among the active Army, Reserve, National Guard, and ROTC attributes; differentiation

Differential diagnosis of hyperkalemia: an update to a complex problem

PubMed Central

Eleftheriadis, T; Leivaditis, K; Antoniadi, G; Liakopoulos, V

2012-01-01

Hyperkalemia is a relative common and sometimes life threatening electorlyte disorder. Although its symptomatic treatment is relatively easy, since precise therapeutic algorithms are available, its differential diagnosis is more complicated. The present review aims to unfold the differential diagnosis of hypekalemia using a pathophysiological, albeit clinically useful, approach. The basic elements of potassium homeostasis are provided, the causes of hyperkalemia are categorized and analysed and finally the required for the diferrential diagnosis laboratory tests are mentioned. PMID:23935306

GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3

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

Boku, Shuken, E-mail: shuboku@med.hokudai.ac.jp; Nakagawa, Shin; Takamura, Naoki

2013-05-17

Highlights: •GDNF has no effect on ADP proliferation and apoptosis. •GDNF increases ADP differentiation into astrocyte. •A specific inhibitor of STAT3 decreases the astrogliogenic effect of GDNF. •STAT3 knockdown by lentiviral shRNA vector also decreases the astrogliogenic effect of GDNF. •GDNF increases the phosphorylation of STAT3. -- Abstract: While the pro-neurogenic actions of antidepressants in the adult hippocampal dentate gyrus (DG) are thought to be one of the mechanisms through which antidepressants exert their therapeutic actions, antidepressants do not increase proliferation of neural precursor cells derived from the adult DG. Because previous studies showed that antidepressants increase the expression andmore » secretion of glial cell line-derived neurotrophic factor (GDNF) in C6 glioma cells derived from rat astrocytes and GDNF increases neurogenesis in adult DG in vivo, we investigated the effects of GDNF on the proliferation, differentiation and apoptosis of cultured neural precursor cells derived from the adult DG. Data showed that GDNF facilitated the differentiation of neural precursor cells into astrocytes but had no effect on their proliferation or apoptosis. Moreover, GDNF increased the phosphorylation of STAT3, and both a specific inhibitor of STAT3 and lentiviral shRNA for STAT3 decreased their differentiation into astrocytes. Taken together, our findings suggest that GDNF facilitates astrogliogenesis from neural precursor cells in adult DG through activating STAT3 and that this action might indirectly affect neurogenesis.« less

Shift of microRNA profile upon orthotopic xenografting of glioblastoma spheroid cultures.

PubMed

Halle, Bo; Thomassen, Mads; Venkatesan, Ranga; Kaimal, Vivek; Marcusson, Eric G; Munthe, Sune; Sørensen, Mia D; Aaberg-Jessen, Charlotte; Jensen, Stine S; Meyer, Morten; Kruse, Torben A; Christiansen, Helle; Schmidt, Steffen; Mollenhauer, Jan; Schulz, Mette K; Andersen, Claus; Kristensen, Bjarne W

2016-07-01

Glioblastomas always recur despite surgery, radiotherapy and chemotherapy. A key player in the therapeutic resistance may be immature tumor cells with stem-like properties (TSCs) escaping conventional treatment. A group of promising molecular targets are microRNAs (miRs). miRs are small non-coding RNAs exerting post-transcriptional regulation of gene expression. In this study we aimed to identify over-expressed TSC-related miRs potentially amenable for therapeutic targeting. We used non-differentiated glioblastoma spheroid cultures (GSCs) containing TSCs and compared these to xenografts using a NanoString nCounter platform. This revealed 19 over-expressed miRs in the non-differentiated GSCs. Additionally, non-differentiated GSCs were compared to neural stem cells (NSCs) using a microarray platform. This revealed four significantly over-expressed miRs in the non-differentiated GSCs in comparison to the NSCs. The three most over-expressed miRs in the non-differentiated GSCs compared to xenografts were miR-126, -137 and -128. KEGG pathway analysis suggested the main biological function of these over-expressed miRs to be cell-cycle arrest and diminished proliferation. To functionally validate the profiling results suggesting association of these miRs with stem-like properties, experimental over-expression of miR-128 was performed. A consecutive limiting dilution assay confirmed a significantly elevated spheroid formation in the miR-128 over-expressing cells. This may provide potential therapeutic targets for anti-miRs to identify novel treatment options for GBM patients.

Myeloma Cell Dynamics in Response to Treatment Supports a Model of Hierarchical Differentiation and Clonal Evolution.

PubMed

Tang, Min; Zhao, Rui; van de Velde, Helgi; Tross, Jennifer G; Mitsiades, Constantine; Viselli, Suzanne; Neuwirth, Rachel; Esseltine, Dixie-Lee; Anderson, Kenneth; Ghobrial, Irene M; San Miguel, Jesús F; Richardson, Paul G; Tomasson, Michael H; Michor, Franziska

2016-08-15

Since the pioneering work of Salmon and Durie, quantitative measures of tumor burden in multiple myeloma have been used to make clinical predictions and model tumor growth. However, such quantitative analyses have not yet been performed on large datasets from trials using modern chemotherapy regimens. We analyzed a large set of tumor response data from three randomized controlled trials of bortezomib-based chemotherapy regimens (total sample size n = 1,469 patients) to establish and validate a novel mathematical model of multiple myeloma cell dynamics. Treatment dynamics in newly diagnosed patients were most consistent with a model postulating two tumor cell subpopulations, "progenitor cells" and "differentiated cells." Differential treatment responses were observed with significant tumoricidal effects on differentiated cells and less clear effects on progenitor cells. We validated this model using a second trial of newly diagnosed patients and a third trial of refractory patients. When applying our model to data of relapsed patients, we found that a hybrid model incorporating both a differentiation hierarchy and clonal evolution best explains the response patterns. The clinical data, together with mathematical modeling, suggest that bortezomib-based therapy exerts a selection pressure on myeloma cells that can shape the disease phenotype, thereby generating further inter-patient variability. This model may be a useful tool for improving our understanding of disease biology and the response to chemotherapy regimens. Clin Cancer Res; 22(16); 4206-14. ©2016 AACR. ©2016 American Association for Cancer Research.

Silicon isotopes in angrites and volatile loss in planetesimals

PubMed Central

Moynier, Frédéric; Savage, Paul S.; Badro, James; Barrat, Jean-Alix

2014-01-01

Inner solar system bodies, including the Earth, Moon, and asteroids, are depleted in volatile elements relative to chondrites. Hypotheses for this volatile element depletion include incomplete condensation from the solar nebula and volatile loss during energetic impacts. These processes are expected to each produce characteristic stable isotope signatures. However, processes of planetary differentiation may also modify the isotopic composition of geochemical reservoirs. Angrites are rare meteorites that crystallized only a few million years after calcium–aluminum-rich inclusions and exhibit extreme depletions in volatile elements relative to chondrites, making them ideal samples with which to study volatile element depletion in the early solar system. Here we present high-precision Si isotope data that show angrites are enriched in the heavy isotopes of Si relative to chondritic meteorites by 50–100 ppm/amu. Silicon is sufficiently volatile such that it may be isotopically fractionated during incomplete condensation or evaporative mass loss, but theoretical calculations and experimental results also predict isotope fractionation under specific conditions of metal–silicate differentiation. We show that the Si isotope composition of angrites cannot be explained by any plausible core formation scenario, but rather reflects isotope fractionation during impact-induced evaporation. Our results indicate planetesimals initially formed from volatile-rich material and were subsequently depleted in volatile elements during accretion. PMID:25404309

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

Kumar, Ajay; Kant, Shiva; Singh, Sukh Mahendra, E-mail: sukhmahendrasingh@yahoo.com

Targeting of tumor metabolism is emerging as a novel therapeutic strategy against cancer. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been shown to exert a potent tumoricidal action against a variety of tumor cells. The main mode of its antineoplastic action implicates a shift of glycolysis to oxidative metabolism of glucose, leading to generation of cytotoxic reactive oxygen intermediates. However, the effect of DCA on tumor microenvironment, which in turn regulates tumor cell survival; remains speculative to a large extent. It is also unclear if DCA can exert any modulatory effect on the process of hematopoiesis, whichmore » is in a compromised state in tumor-bearing hosts undergoing chemotherapy. In view of these lacunas, the present study was undertaken to investigate the so far unexplored aspects with respect to the molecular mechanisms of DCA-dependent tumor growth retardation and chemosensitization. BALB/c mice were transplanted with Dalton's lymphoma (DL) cells, a T cell lymphoma of spontaneous origin, followed by administration of DCA with or without cisplatin. DCA-dependent tumor regression and chemosensitization to cisplatin was found to be associated with altered repertoire of key cell survival regulatory molecules, modulated glucose metabolism, accompanying reconstituted tumor microenvironment with respect to pH homeostasis, cytokine balance and alternatively activated TAM. Moreover, DCA administration also led to an alteration in the MDR phenotype of tumor cells and myelopoietic differentiation of macrophages. The findings of this study shed a new light with respect to some of the novel mechanisms underlying the antitumor action of DCA and thus may have immense clinical applications. - Highlights: • DCA modulates tumor progression and chemoresistance. • DCA alters molecules regulating cell survival, glucose metabolism and MDR. • DCA reconstitutes biophysical and cellular composition of tumor microenvironment. • DCA augments BMC cellularity, differentiation and repolarization of macrophages.« less

Repair of Segmental Bone Defect Using Totally Vitalized Tissue Engineered Bone Graft by a Combined Perfusion Seeding and Culture System

PubMed Central

Feng, Ya-Fei; Li, Xiang; Hu, Yun-Yu; Wang, Zhen; Ma, Zhen-Sheng; Lei, Wei

2014-01-01

Background The basic strategy to construct tissue engineered bone graft (TEBG) is to combine osteoblastic cells with three dimensional (3D) scaffold. Based on this strategy, we proposed the “Totally Vitalized TEBG” (TV-TEBG) which was characterized by abundant and homogenously distributed cells with enhanced cell proliferation and differentiation and further investigated its biological performance in repairing segmental bone defect. Methods In this study, we constructed the TV-TEBG with the combination of customized flow perfusion seeding/culture system and β-tricalcium phosphate (β-TCP) scaffold fabricated by Rapid Prototyping (RP) technique. We systemically compared three kinds of TEBG constructed by perfusion seeding and perfusion culture (PSPC) method, static seeding and perfusion culture (SSPC) method, and static seeding and static culture (SSSC) method for their in vitro performance and bone defect healing efficacy with a rabbit model. Results Our study has demonstrated that TEBG constructed by PSPC method exhibited better biological properties with higher daily D-glucose consumption, increased cell proliferation and differentiation, and better cell distribution, indicating the successful construction of TV-TEBG. After implanted into rabbit radius defects for 12 weeks, PSPC group exerted higher X-ray score close to autograft, much greater mechanical property evidenced by the biomechanical testing and significantly higher new bone formation as shown by histological analysis compared with the other two groups, and eventually obtained favorable healing efficacy of the segmental bone defect that was the closest to autograft transplantation. Conclusion This study demonstrated the feasibility of TV-TEBG construction with combination of perfusion seeding, perfusion culture and RP technique which exerted excellent biological properties. The application of TV-TEBG may become a preferred candidate for segmental bone defect repair in orthopedic and maxillofacial fields. PMID:24728277

Differential effectiveness of selected non-psychotropic phytocannabinoids on human sebocyte functions implicates their introduction in dry/seborrhoeic skin and acne treatment.

PubMed

Oláh, Attila; Markovics, Arnold; Szabó-Papp, Judit; Szabó, Pálma Tímea; Stott, Colin; Zouboulis, Christos C; Bíró, Tamás

2016-09-01

Acne is a common skin disease characterized by elevated sebum production and inflammation of the sebaceous glands. We have previously shown that a non-psychotropic phytocannabinoid ((-)-cannabidiol [CBD]) exerted complex anti-acne effects by normalizing 'pro-acne agents'-induced excessive sebaceous lipid production, reducing proliferation and alleviating inflammation in human SZ95 sebocytes. Therefore, in this study we aimed to explore the putative anti-acne effects of further non-psychotropic phytocannabinoids ((-)-cannabichromene [CBC], (-)-cannabidivarin [CBDV], (-)-cannabigerol [CBG], (-)-cannabigerovarin [CBGV] and (-)-Δ(9) -tetrahydrocannabivarin [THCV]). Viability and proliferation of human SZ95 sebocytes were investigated by MTT and CyQUANT assays; cell death and lipid synthesis were monitored by DilC1 (5)-SYTOX Green labelling and Nile Red staining, respectively. Inflammatory responses were investigated by monitoring expressions of selected cytokines upon lipopolysaccharide treatment (RT-qPCR, ELISA). Up to 10 μm, the phytocannabinoids only negligibly altered the viability of the sebocytes, whereas high doses (≥50 μm) induced apoptosis. Interestingly, basal sebaceous lipid synthesis was differentially modulated by the substances: CBC and THCV suppressed it, and CBDV had only minor effects, whereas CBG and CBGV increased it. Importantly, CBC, CBDV and THCV significantly reduced arachidonic acid (AA)-induced 'acne-like' lipogenesis. Moreover, THCV suppressed proliferation, and all phytocannabinoids exerted remarkable anti-inflammatory actions. Our data suggest that CBG and CBGV may have potential in the treatment of dry-skin syndrome, whereas CBC, CBDV and especially THCV show promise to become highly efficient, novel anti-acne agents. Moreover, based on their remarkable anti-inflammatory actions, phytocannabinoids could be efficient, yet safe novel tools in the management of cutaneous inflammations. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Investigation of the Differential Contributions of Superficial and Deep Muscles on Cervical Spinal Loads with Changing Head Postures

PubMed Central

Cheng, Chih-Hsiu; Chien, Andy; Hsu, Wei-Li; Chen, Carl Pai-Chu; Cheng, Hsin-Yi Kathy

2016-01-01

Cervical spinal loads are predominately influenced by activities of cervical muscles. However, the coordination between deep and superficial muscles and their influence on the spinal loads is not well understood. This study aims to document the changes of cervical spinal loads and the differential contributions of superficial and deep muscles with varying head postures. Electromyography (EMG) of cervical muscles from seventeen healthy adults were measured during maximal isometric exertions for lateral flexion (at 10°, 20° and terminal position) as well as flexion/extension (at 10°, 20°, 30°, and terminal position) neck postures. An EMG-assisted optimization approach was used to estimate the muscle forces and subsequent spinal loads. The results showed that compressive and anterior-posterior shear loads increased significantly with neck flexion. In particular, deep muscle forces increased significantly with increasing flexion. It was also determined that in all different static head postures, the deep muscle forces were greater than those of the superficial muscle forces, however, such pattern was reversed during peak efforts where greater superficial muscle forces were identified with increasing angle of inclination. In summary, the identification of significantly increased spinal loads associated with increased deep muscle activation during flexion postures, implies higher risks in predisposing the neck to occupationally related disorders. The results also explicitly supported that deep muscles play a greater role in maintaining stable head postures where superficial muscles are responsible for peak exertions and reinforcing the spinal stability at terminal head postures. This study provided quantitative data of normal cervical spinal loads and revealed motor control strategies in coordinating the superficial and deep muscles during physical tasks. PMID:26938773

Investigation of the Differential Contributions of Superficial and Deep Muscles on Cervical Spinal Loads with Changing Head Postures.

PubMed

Cheng, Chih-Hsiu; Chien, Andy; Hsu, Wei-Li; Chen, Carl Pai-Chu; Cheng, Hsin-Yi Kathy

2016-01-01

Cervical spinal loads are predominately influenced by activities of cervical muscles. However, the coordination between deep and superficial muscles and their influence on the spinal loads is not well understood. This study aims to document the changes of cervical spinal loads and the differential contributions of superficial and deep muscles with varying head postures. Electromyography (EMG) of cervical muscles from seventeen healthy adults were measured during maximal isometric exertions for lateral flexion (at 10°, 20° and terminal position) as well as flexion/extension (at 10°, 20°, 30°, and terminal position) neck postures. An EMG-assisted optimization approach was used to estimate the muscle forces and subsequent spinal loads. The results showed that compressive and anterior-posterior shear loads increased significantly with neck flexion. In particular, deep muscle forces increased significantly with increasing flexion. It was also determined that in all different static head postures, the deep muscle forces were greater than those of the superficial muscle forces, however, such pattern was reversed during peak efforts where greater superficial muscle forces were identified with increasing angle of inclination. In summary, the identification of significantly increased spinal loads associated with increased deep muscle activation during flexion postures, implies higher risks in predisposing the neck to occupationally related disorders. The results also explicitly supported that deep muscles play a greater role in maintaining stable head postures where superficial muscles are responsible for peak exertions and reinforcing the spinal stability at terminal head postures. This study provided quantitative data of normal cervical spinal loads and revealed motor control strategies in coordinating the superficial and deep muscles during physical tasks.

SCG postnatal remodelling--hypertrophy and neuron number stability--in Spix's yellow-toothed cavies (Galea spixii).

PubMed

Ladd, Aliny A B Lobo; Ladd, Fernando V Lobo; da Silva, Andrea A P; Oliveira, Moacir F; de Souza, Romeu R; Coppi, Antonio A

2012-04-01

Whilst a fall in neuron numbers seems a common pattern during postnatal development, several authors have nonetheless reported an increase in neuron number, which may be associated with any one of a number of possible processes encapsulating either neurogenesis or late maturation and incomplete differentiation. Recent publications have thus added further fuel to the notion that a postnatal neurogenesis may indeed exist in sympathetic ganglia. In the light of these uncertainties surrounding the effects exerted by postnatal development on the number of superior cervical ganglion (SCG) neurons, we have used state-of-the-art design-based stereology to investigate the quantitative structure of SCG at four distinct timepoints after birth, viz., 1-3 days, 1 month, 12 months and 36 months. The main effects exerted by ageing on the SCG structure were: (i) a 77% increase in ganglion volume; (ii) stability in the total number of the whole population of SCG nerve cells (no change--either increase or decrease) during post-natal development; (iii) a higher proportion of uninucleate neurons to binucleate neurons only in newborn animals; (iv) a 130% increase in the volume of uninucleate cell bodies; and (v) the presence of BrdU positive neurons in animals at all ages. At the time of writing our results support the idea that neurogenesis takes place in the SCG of preás, albeit it warrants confirmation by further markers. We also hypothesise that a portfolio of other mechanisms: cell repair, maturation, differentiation and death may be equally intertwined and implicated in the numerical stability of SCG neurons during postnatal development. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

Secretion of immunoregulatory cytokines by mesenchymal stem cells

PubMed Central

Kyurkchiev, Dobroslav; Bochev, Ivan; Ivanova-Todorova, Ekaterina; Mourdjeva, Milena; Oreshkova, Tsvetelina; Belemezova, Kalina; Kyurkchiev, Stanimir

2014-01-01

According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells (MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when cultured under standard conditions, express a certain panel of phenotypic markers and can differentiate into osteogenic, chondrogenic and adipogenic lineages when cultured in specific inducing media. In parallel with their major role as undifferentiated cell reserves, MSCs have immunomodulatory functions which are exerted by direct cell-to-cell contacts, secretion of cytokines and/or by a combination of both mechanisms. There are no convincing data about a principal difference in the profile of cytokines secreted by MSCs isolated from different tissue sources, although some papers report some quantitative but not qualitative differences in cytokine secretion. The present review focuses on the basic cytokines secreted by MSCs as described in the literature by which the MSCs exert immunodulatory effects. It should be pointed out that MSCs themselves are objects of cytokine regulation. Hypothetical mechanisms by which the MSCs exert their immunoregulatory effects are also discussed in this review. These mechanisms may either influence the target immune cells directly or indirectly by affecting the activities of predominantly dendritic cells. Chemokines are also discussed as participants in this process by recruiting cells of the immune systems and thus making them targets of immunosuppression. This review aims to present and discuss the published data and the personal experience of the authors regarding cytokines secreted by MSCs and their effects on the cells of the immune system. PMID:25426252

Maternal Diet, Metabolic State, and Inflammatory Response Exert Unique and Long-Lasting Influences on Offspring Behavior in Non-Human Primates

PubMed Central

Thompson, Jacqueline R.; Gustafsson, Hanna C.; DeCapo, Madison; Takahashi, Diana L.; Bagley, Jennifer L.; Dean, Tyler A.; Kievit, Paul; Fair, Damien A.; Sullivan, Elinor L.

2018-01-01

Nutritional status influences brain health and gestational exposure to metabolic disorders (e.g. obesity and diabetes) increases the risk of neuropsychiatric disorders. The aim of the present study was to further investigate the role of maternal Western-style diet (WSD), metabolic state, and inflammatory factors in the programming of Japanese macaque offspring behavior. Utilizing structural equation modeling, we investigated the relationships between maternal diet, prepregnancy adiposity, third trimester insulin response, and plasma cytokine levels on 11-month-old offspring behavior. Maternal WSD was associated with greater reactive and ritualized anxiety in offspring. Maternal adiposity and third trimester macrophage-derived chemokine (MDC) exerted opposing effects on offspring high-energy outbursts. Elevated levels of this behavior were associated with low maternal MDC and increased prepregnancy adiposity. This is the first study to show that maternal MDC levels influence offspring behavior. We found no evidence suggesting maternal peripheral inflammatory response mediated the effect of maternal diet and metabolic state on aberrant offspring behavior. Additionally, the extent of maternal metabolic impairment differentially influenced chemokine response. Elevated prepregnancy adiposity suppressed third trimester chemokines, while obesity-induced insulin resistance augmented peripheral chemokine levels. WSD also directly increased maternal interleukin-12. This is the first non-human primate study to delineate the effects of maternal diet and metabolic state on gestational inflammatory environment and subsequent offspring behavior. Our findings give insight to the complex mechanisms by which diet, metabolic state, and inflammation during pregnancy exert unique influences on offspring behavioral regulation. PMID:29740395

Feasibility of estimating cementation rates in a brittle fault zone using Sr/Ca partition coefficients for sedimentary diagenesis

NASA Astrophysics Data System (ADS)

Hadizadeh, Jafar; Foit, Franklin F.

2000-04-01

Cement phases such as calcite or quartz often incorporate trace elements from the parent fluids as they crystallize. Experimental sedimentary diagenesis indicates that trace element partition coefficients reflect rates of cementation. The applicability of these findings to fault zone cementation is examined as we make a preliminary attempt to estimate calcite cementation rate in a brittle fault zone directly from the fault-rock composition data. Samples for this study were collected from the Knoxville outcrop of the Saltville fault in Tennessee. The cementation rates for the fault rock samples range from 1×10 -12 to 3×10 -13 m3/ h per m, in agreement with some experimental rates and the rates reported for samples from the DSDP sites. When applied to a non-responsive pore-system model, these rates result in rapid precipitation sealing indicating the influence exerted by the surface-area/volume ratio of the pore network. We find it feasible to obtain a reasonable range of values for the cementation rate using the trace element partition method. However, the study also indicates the need for relatively accurate values for the trace/carrier element ratio in the fault zone syntectonic pore fluid, and exhumed cement.

Activity of genes with functions in human Williams-Beuren Syndrome are impacted by mobile element insertions in the gray wolf genome.

PubMed

vonHoldt, Bridgett M; Ji, Sarah S; Aardema, Matthew L; Stahler, Daniel; Udell, Monique A R; Sinsheimer, Janet S

2018-06-01

In canines, transposon dynamics have been associated with a hyper-social behavioral syndrome, although the functional mechanism has yet to be described. We investigate the epigenetic and transcriptional consequences of these behavior-associated mobile element insertions in dogs and Yellowstone wolves. We posit that the transposons themselves may not be the causative feature; rather, their transcriptional regulation may exert the functional impact. We survey four outlier transposons associated with hyper-sociability, with the expectation that they are targeted for epigenetic silencing. We predict hyper-methylation of mobile element insertions (MEIs), suggestive that the epigenetic silencing of and not the MEIs themselves may be driving dysregulation of nearby genes. We found that transposon-derived sequences are significantly hyper-methylated, regardless of their copy number or species. Further, we have assessed transcriptome sequence data and found evidence that mobile element insertions impact the expression levels of six genes (WBSCR17, LIMK1, GTF2I, WBSCR27, BAZ1B, and BCL7B), all of which have known roles in human Williams-Beuren syndrome due to changes in copy number, typically hemizygosity. Although further evidence is needed, our results suggest that a few insertions alter local expression at multiple genes, likely through a cis-regulatory mechanism that excludes proximal methylation.

Glial Modulation by N-acylethanolamides in Brain Injury and Neurodegeneration

PubMed Central

Herrera, María I.; Kölliker-Frers, Rodolfo; Barreto, George; Blanco, Eduardo; Capani, Francisco

2016-01-01

Neuroinflammation involves the activation of glial cells and represents a key element in normal aging and pathophysiology of brain damage. N-acylethanolamides (NAEs), naturally occurring amides, are known for their pro-homeostatic effects. An increase in NAEs has been reported in vivo and in vitro in the aging brain and in brain injury. Treatment with NAEs may promote neuroprotection and exert anti-inflammatory actions via PPARα activation and/or by counteracting gliosis. This review aims to provide an overview of endogenous and exogenous properties of NAEs in neuroinflammation and to discuss their interaction with glial cells. PMID:27199733

Glial Modulation by N-acylethanolamides in Brain Injury and Neurodegeneration.

PubMed

Herrera, María I; Kölliker-Frers, Rodolfo; Barreto, George; Blanco, Eduardo; Capani, Francisco

2016-01-01

Neuroinflammation involves the activation of glial cells and represents a key element in normal aging and pathophysiology of brain damage. N-acylethanolamides (NAEs), naturally occurring amides, are known for their pro-homeostatic effects. An increase in NAEs has been reported in vivo and in vitro in the aging brain and in brain injury. Treatment with NAEs may promote neuroprotection and exert anti-inflammatory actions via PPARα activation and/or by counteracting gliosis. This review aims to provide an overview of endogenous and exogenous properties of NAEs in neuroinflammation and to discuss their interaction with glial cells.

[The functions of calcium-sensing receptor in regulating mineral metabolism.

PubMed

Kinoshita, Yuka

Calcium-sensing receptor(CaSR)which belongs to a G protein-coupled receptor family is one of the key elements in regulating calcium homeostasis. CaSR has been identified as a receptor to control parathyroid hormone(PTH)secretion in parathyroid glands according to serum calcium ion(Ca2+)levels. It has also been shown that CaSR controls reabsorption of water and several cations including Ca2+and magnesium ion(Mg2+)in renal tubular cells. This review summarizes the functions and roles of CaSR in mineral metabolism that are exerted in parathyroid glands, kidney, and intestine.

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.

Involvement of the histamine H{sub 4} receptor in clozapine-induced hematopoietic toxicity: Vulnerability under granulocytic differentiation of HL-60 cells

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

Goto, Aya; Mouri, Akihiro; Nagai, Tomoko

Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but can cause fatal hematopoietic toxicity as agranulocytosis. To elucidate the mechanism of hematopoietic toxicity induced by clozapine, we developed an in vitro assay system using HL-60 cells, and investigated the effect on hematopoiesis. HL-60 cells were differentiated by all-trans retinoic acid (ATRA) into three states according to the following hematopoietic process: undifferentiated HL-60 cells, those undergoing granulocytic ATRA-differentiation, and ATRA-differentiated granulocytic cells. Hematopoietic toxicity was evaluated by analyzing cell survival, cell proliferation, granulocytic differentiation, apoptosis, and necrosis. In undifferentiated HL-60 cells and ATRA-differentiated granulocytic cells, both clozapine (50 and 100 μM)more » and doxorubicin (0.2 µM) decreased the cell survival rate, but olanzapine (1–100 µM) did not. Under granulocytic differentiation for 5 days, clozapine, even at a concentration of 25 μM, decreased survival without affecting granulocytic differentiation, increased caspase activity, and caused apoptosis rather than necrosis. Histamine H{sub 4} receptor mRNA was expressed in HL-60 cells, whereas the expression decreased under granulocytic ATRA-differentiation little by little. Both thioperamide, a histamine H{sub 4} receptor antagonist, and DEVD-FMK, a caspase-3 inhibitor, exerted protection against clozapine-induced survival rate reduction, but not of live cell counts. 4-Methylhistamine, a histamine H{sub 4} receptor agonist, decreased the survival rate and live cell counts, as did clozapine. HL-60 cells under granulocytic differentiation are vulnerable under in vitro assay conditions to hematopoietic toxicity induced by clozapine. Histamine H{sub 4} receptor is involved in the development of clozapine-induced hematopoietic toxicity through apoptosis, and may be a potential target for preventing its occurrence through granulocytic differentiation. - Highlights: • HL-60 cells under granulocytic differentiation were vulnerable for clozapine. • HL-60 cells would be in vitro assay systems for hematopoietic toxicity by clozapine. • Histamine H{sub 4} receptor was involved in hematopoietic toxicity with apoptosis. • Histamine H{sub 4} receptor may be therapeutic target to prevent hematopoietic toxicity.« less

Parvovirus-Derived Endogenous Viral Elements in Two South American Rodent Genomes

PubMed Central

2014-01-01

We describe endogenous viral elements (EVEs) derived from parvoviruses (family Parvoviridae) in the genomes of the long-tailed chinchilla (Chinchilla lanigera) and the degu (Octodon degus). The novel EVEs include dependovirus-related elements and representatives of a clearly distinct parvovirus lineage that also has endogenous representatives in marsupial genomes. In the degu, one dependovirus-derived EVE was found to carry an intact reading frame and was differentially expressed in vivo, with increased expression in the liver. PMID:25078696

Chemical studies of differentiated meteorites. I - Labile trace elements in Antarctic and non-Antarctic eucrites

NASA Technical Reports Server (NTRS)

Paul, Rick L.; Lipschutz, Michael E.

1990-01-01

Element contents of Ag, Au, Bi, Cd, Co, Cs, Ga, In, Rb, Sb, Se, Te, Tl, U, and Zn were analyzed, using RNAA, in 25 Antarctic and nine non-Antarctic eucrites to determine whether these two populations differ significantly in thermal history and derive from the same or different eucrite parent body. Data for these 15 elements indicate that basaltic Antarctic and non-Antarctic eucrite populations reflect the same genetic processes and, hence, come from the same parent asteroid.

Biphasic effects of FGF2 on odontoblast differentiation involve changes in the BMP and Wnt signaling pathways.

PubMed

Sagomonyants, Karen; Mina, Mina

2014-08-01

Odontoblast differentiation during physiological and reparative dentinogenesis is dependent upon multiple signaling molecules, including fibroblast growth factors (FGFs), bone morphogenetic proteins (BMPs) and Wingless/Integrated (Wnt) ligands. Recent studies in our laboratory showed that continuous exposure of primary dental pulp cultures to FGF2 exerted biphasic effects on the expression of markers of dentinogenesis. In the present study, we examined the possible involvement of the BMP and Wnt signaling pathways in mediating the effects of FGF2 on dental pulp cells. Our results showed that stimulatory effects of FGF2 on dentinogenesis during the proliferation phase of growth were associated with increased expression of the components of the BMP (Bmp2, Dlx5, Msx2, Osx) and Wnt (Wnt10a, Wisp2) pathways, and decreased expression of an inhibitor of the Wnt signaling, Nkd2. Further addition of FGF2 during the differentiation/mineralization phase of growth resulted in decreased expression of components of the BMP signaling (Bmp2, Runx2, Osx) and increased expression of inhibitors of the Wnt signaling (Nkd2, Dkk3). This suggests that both BMP and Wnt pathways may be involved in mediating the effects of FGF2 on dental pulp cells.

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

PubMed Central

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

2011-01-01

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

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

PubMed

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

2011-07-01

Whole body vibration (WBV), consisting of a low-magnitude, high-frequency (LMHF) signal, is anabolic to bone in vivo and may act through alteration of the lineage commitment of mesenchymal stromal cells (MSC). We investigated the effect of LMHF vibration on rat bone marrow-derived MSCs (rMSCs) in an in vitro system. We subjected rMSCs to repeated (six) bouts of 1-h vibration at 0.3g and 60 Hz in the presence of osteogenic (OS) induction medium. The OS differentiation of rMSCs under the loaded and non-loaded conditions was assessed by examining cell proliferation, alkaline phosphatase (ALP) activity, mRNA expression of various osteoblast-associated markers [ALP, Runx2, osterix (Osx), collagen type I alpha 1 (COL1A1), bone sialoprotein (BSP), osteopontin (OPN), and osteocalcin (OCN)], and matrix mineralization. LMHF vibration did not enhance the OS differentiation of rMSCs. Surprisingly, the mRNA level of Osx, a transcription factor necessary for osteoblast formation, was decreased, and matrix mineralization was inhibited. Our findings suggest that LMHF vibration may exert its anabolic effects in vivo via mechanosensing of a cell type different from MSCs. Copyright © 2011 Orthopaedic Research Society.

Extrinsic and intrinsic mechanisms by which mesenchymal stem cells suppress the immune system

PubMed Central

Coulson-Thomas, Vivien J.; Coulson-Thomas, Yvette M.; Gesteira, Tarsis F.; Kao, Winston W.-Y.

2016-01-01

Mesenchymal stem cells (MSCs) are a group of fibroblast-like multipotent mesenchymal stromal cells that have the ability to differentiate into osteoblasts, adipocytes, and chondrocytes. Recent studies have demonstrated that MSCs possess a unique ability to exert suppressive and regulatory effects on both adaptive and innate immunity in an autologous and allogeneic manner. A vital step in stem cell transplantation is overcoming the potential graft-versus-host disease, which is a limiting factor to transplantation success. Given that MSCs attain powerful differentiation capabilities and also present immunosuppressive properties, which enable them to survive host immune rejection, MSCs are of great interest. Due to their ability to differentiate into different cell types and to suppress and modulate the immune system, MSCs are being developed for treating a plethora of diseases, including immune disorders. Moreover, in recent years, MSCs have been genetically engineered to treat and sometimes even cure some diseases, and the use of MSCs for cell therapy presents new perspectives for overcoming tissue rejection. In this review, we discuss the potential extrinsic and intrinsic mechanisms that underlie MSCs’ unique ability to modulate inflammation, and both innate and adaptive immunity. PMID:26804815

A Study of the Differential Effects of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) on Gene Expression Profiles of Stimulated Thp-1 Macrophages.

PubMed

Allam-Ndoul, Bénédicte; Guénard, Frédéric; Barbier, Olivier; Vohl, Marie-Claude

2017-04-25

Background: An appropriate intake of omega-3 ( n -3) fatty acids (FAs) such as eicosapentaenoic and docosahexaenoic acid (EPA/DHA) from marine sources is known to have anti-inflammatory effects. However, molecular mechanisms underlying their beneficial effects on health are not fully understood. The aim of the present study was to characterize gene expression profiles of THP-1 macrophages, incubated in either EPA or DHA and stimulated with lipopolysaccharide (LPS), a pro-inflammatory agent. Methods: THP-1 macrophages were incubated into 10, 50 and 75 µM of EPA or DHA for 24 h, and 100 nM of LPS was added to the culture media for 18 h. Total mRNA was extracted and gene expression examined by microarray analysis using Illumina Human HT-12 expression beadchips (Illumina). Results: Pathway analysis revealed that EPA and DHA regulate genes involved in cell cycle regulation, apoptosis, immune response and inflammation, oxidative stress and cancer pathways in a differential and dose-dependent manner. Conclusions: EPA and DHA appear to exert differential effects on gene expression in THP-1 macrophages. Specific effects of n -3 FAs on gene expression levels are also dose-dependent.

Differential wall growth in gravistimulated corn roots: Its timing and regulation

NASA Technical Reports Server (NTRS)

Serlin, B. S.

1985-01-01

The experiments designed to document cell-wall level changes which occur as a result of their gravistimulation are described. The goal of this research is to elucidate the mechanism and time frame of differential growth following a controlled gravistimulation. To achieve this, rates of wall deposition will be determined by following the incorporation of radioactive monosaccharides into the wall. Complementing this experiment will be a freeze-etch study directed at revealing the spatial arrangment of both newly-deposited microfibrils and microfibrils that were present in the growing root prior to stimulation. The second phase of the proposed research will examine the roles ethylene and Ca(2+) have in the modulation of differential wall changes during gravitropism. Ethylene and Ca(2+) have both been implicated as regulators of the gravitropic response in roots and they have also been implicated as regulators of the gravitropic response in roots and they have also been reported to exert some control on the orientation of microfibrils. Both of these agents will be manipulated in such a way as to reveal whether they have a direct influence on cell wall deposition and microfibrillar alignment during the geotropic response.

Differentiation-associated microRNAs antagonize the Rb–E2F pathway to restrict proliferation

PubMed Central

Marzi, Matteo J.; Puggioni, Eleonora M. R.; Dall'Olio, Valentina; Bucci, Gabriele; Bernard, Loris; Bianchi, Fabrizio; Crescenzi, Marco

2012-01-01

The cancer-associated loss of microRNA (miRNA) expression leads to a proliferative advantage and aggressive behavior through largely unknown mechanisms. Here, we exploit a model system that recapitulates physiological terminal differentiation and its reversal upon oncogene expression to analyze coordinated mRNA/miRNA responses. The cell cycle reentry of myotubes, forced by the E1A oncogene, was associated with a pattern of mRNA/miRNA modulation that was largely reciprocal to that induced during the differentiation of myoblasts into myotubes. The E1A-induced mRNA response was preponderantly Retinoblastoma protein (Rb)-dependent. Conversely, the miRNA response was mostly Rb-independent and exerted through tissue-specific factors and Myc. A subset of these miRNAs (miR-1, miR-34, miR-22, miR-365, miR-29, miR-145, and Let-7) was shown to coordinately target Rb-dependent cell cycle and DNA replication mRNAs. Thus, a dual level of regulation—transcriptional regulation via Rb–E2F and posttranscriptional regulation via miRNAs—confers robustness to cell cycle control and provides a molecular basis to understand the role of miRNA subversion in cancer. PMID:23027903

Mesenchymal Stem Cells for Cartilage Regeneration of TMJ Osteoarthritis

PubMed Central

Li, Hongyu; Xu, Xin; Ye, Ling; Zhou, Xuedong

2017-01-01

Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative disease, characterized by progressive cartilage degradation, subchondral bone remodeling, synovitis, and chronic pain. Due to the limited self-healing capacity in condylar cartilage, traditional clinical treatments have limited symptom-modifying and structure-modifying effects to restore impaired cartilage as well as other TMJ tissues. In recent years, stem cell-based therapy has raised much attention as an alternative approach towards tissue repair and regeneration. Mesenchymal stem cells (MSCs), derived from the bone marrow, synovium, and even umbilical cord, play a role as seed cells for the cartilage regeneration of TMJ OA. MSCs possess multilineage differentiation potential, including chondrogenic differentiation as well as osteogenic differentiation. In addition, the trophic modulations of MSCs exert anti-inflammatory and immunomodulatory effects under aberrant conditions. Furthermore, MSCs combined with appropriate scaffolds can form cartilaginous or even osseous compartments to repair damaged tissue and impaired function of TMJ. In this review, we will briefly discuss the pathogenesis of cartilage degeneration in TMJ OA and emphasize the potential sources of MSCs and novel approaches for the cartilage regeneration of TMJ OA, particularly focusing on the MSC-based therapy and tissue engineering. PMID:29123550

Low pulse energy Nd:YAG laser irradiation exerts a biostimulative effect on different cells of the oral microenvironment: "an in vitro study".

PubMed

Chellini, Flaminia; Sassoli, Chiara; Nosi, Daniele; Deledda, Cristiana; Tonelli, Paolo; Zecchi-Orlandini, Sandra; Formigli, Lucia; Giannelli, Marco

2010-08-01

Dental lasers represent a promising therapeutic tool in the treatment of periodontal and peri-implant diseases. However, their clinical application remains still limited. Here, we investigated the potential biostimulatory effect of low pulse energy neodymium:yttrium-aluminum-garnet (Nd:YAG) laser irradiation on different cells representative of the oral microenvironment and elucidated the underlying molecular mechanisms. Saos-2 osteoblasts, H-end endothelial cells, and NIH/3T3 fibroblasts pre-treated or not with photosensitizing dye methylene blue (MB), were irradiated with low pulse energy (20 mJ) and high repetition rate (50-70 Hz) Nd:YAG laser, and evaluated for cell viability and proliferation as well as for the expression of specific differentiation markers by confocal immunofluorescence and real-time RT-PCR. Changes in intracellular Ca(2+) levels after laser exposure were also evaluated in living osteoblasts. Nd:YAG laser irradiation did not affect cell viability in all the tested cell types, even when combined with pre-treatment with MB, and efficiently stimulated cell growth in the non-sensitized osteoblasts. Moreover, a significant induction in the expression of osteopontin, ALP, and Runx2 in osteoblasts, type I collagen in fibroblasts, and vinculin in endothelial cells could be observed in the irradiated cells. Pre-treatment with MB negatively affected cell differentiation in the unstimulated and laser-stimulated cells. Notably, laser irradiation also caused an increase in the intracellular Ca(2+) in osteoblasts through the activation of TRPC1 ion channels. Moreover, the pharmacologic or genetic inhibition of these channels strongly attenuated laser-induced osteopontin expression, suggesting a role for the laser-mediated Ca(2+) influx in regulating osteoblast differentiation. Low pulse energy and high repetition rate Nd:YAG laser irradiation may exert a biostimulative effect on different cells representative of the oral microenvironment, particularly osteoblasts. Pre-treatment with MB prior to irradiation hampers this effect and limits the potential clinical application of photosensitizing dyes in dental practice. (c) 2010 Wiley-Liss, Inc.

Antioxidant and Renoprotective Effects of Mushroom Extract: Implication in Prevention of Nephrolithiasis

PubMed Central

Schulman, Ariel; Chaimowitz, Matthew; Choudhury, Muhammad; Eshghi, Majid; Konno, Sensuke

2016-01-01

Background The pathogenesis of nephrolithiasis (kidney stone) remains elusive, while several therapeutic options are available but not effective as we expected. Accumulating data yet suggest that oxidative stress (generation of oxygen free radicals) may play a primary role in its occurrence. Particularly, calcium oxalate (CaOx) is a key element in the most common form (> 75%) of kidney stones, and its crystal form known as CaOx monohydrate (COM) has been shown to exert oxidative stress, facilitating CaOx stone formation. Hence, diminishing oxidative stress with certain antioxidants could be a potential strategic approach. We are interested in a bioactive extract of Poria mushroom, PE, which has been shown to have antioxidant and renoprotective activities. Accordingly, we investigated if PE might have antioxidant activity that would have implication in prevention of kidney stone formation. Methods Renal epithelial LLC-PK1 cells were employed and exposed to COM or hydrogen peroxide (H2O2) as a positive control capable of exerting oxidative stress. Possible antioxidant and protective effects of PE against oxidative stress (exerted by COM or H2O2) were assessed by cell viability test and lipid peroxidation (LPO) assay. To explore its protective mechanism, two glycolytic parameters, hexokinase (HK) activity and ATP synthesis, were examined and cell cycle analysis was also performed. Results Both H2O2 and COM led to a significant (P < 0.05) reduction in cell viability, accompanied by severe oxidative stress assessed by LPO assay. Such oxidative stress also caused the significant decline in HK activity and cellular ATP level, indicating the inhibition of glycolysis. Cell cycle analysis further indicated that oxidative stress interfered with cell cycle, inducing a G1 cell cycle arrest that presumably results in the cessation of cell proliferation. However, PE was capable of significantly preventing or diminishing all these cellular effects mediated through oxidative stress (exerted by H2O2 and COM). Conclusions The present study shows that the mushroom extract PE appears to have antioxidant and renoprotective effects against oxidative stress exerted by COM in renal cells. Therefore, PE with antioxidant activity is considered a promising natural agent that may have clinical implications in prevention of nephrolithiasis primarily induced by oxidative stress. PMID:27829958

Differential CLE peptide perception by plant receptors implicated from structural and functional analyses of TDIF-TDR interactions

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

Li, Zhijie; Chakraborty, Sayan; Xu, Guozhou

Tracheary Element Differentiation Inhibitory Factor (TDIF) belongs to the family of post-translationally modified CLE (CLAVATA3/embryo surrounding region (ESR)-related) peptide hormones that control root growth and define the delicate balance between stem cell proliferation and differentiation in SAM (shoot apical meristem) or RAM (root apical meristem). In Arabidopsis, Tracheary Element Differentiation Inhibitory Factor Receptor (TDR) and its ligand TDIF signaling pathway is involved in the regulation of procambial cell proliferation and inhibiting its differentiation into xylem cells. Here we present the crystal structures of the extracellular domains (ECD) of TDR alone and in complex with its ligand TDIF resolved at 2.65more » Åand 2.75 Å respectively. These structures provide insights about the ligand perception and specific interactions between the CLE peptides and their cognate receptors. Our in vitro biochemical studies indicate that the interactions between the ligands and the receptors at the C-terminal anchoring site provide conserved binding. While the binding interactions occurring at the N-terminal anchoring site dictate differential binding specificities between different ligands and receptors. Our studies will open different unknown avenues of TDR-TDIF signaling pathways that will enhance our knowledge in this field highlighting the receptor ligand interaction, receptor activation, signaling network, modes of action and will serve as a structure function relationship model between the ligand and the receptor for various similar leucine-rich repeat receptor-like kinases (LRR-RLKs).« less

Adhesive pad differentiation in Drosophila melanogaster depends on the Polycomb group gene Su(z)2.

PubMed

Hüsken, Mirko; Hufnagel, Kim; Mende, Katharina; Appel, Esther; Meyer, Heiko; Peisker, Henrik; Tögel, Markus; Wang, Shuoshuo; Wolff, Jonas; Gorb, Stanislav N; Paululat, Achim

2015-04-15

The ability of many insects to walk on vertical smooth surfaces such as glass or even on the ceiling has fascinated biologists for a long time, and has led to the discovery of highly specialized adhesive organs located at the distal end of the animals' legs. So far, research has primarily focused on structural and ultrastructural investigations leading to a deeper understanding of adhesive organ functionality and to the development of new bioinspired materials. Genetic approaches, e.g. the analysis of mutants, to achieve a better understanding of adhesive organ differentiation have not been used so far. Here, we describe the first Drosophila melanogaster mutant that develops malformed adhesive organs, resulting in a complete loss of climbing ability on vertical smooth surfaces. Interestingly, these mutants fail to make close contact between the setal tips and the smooth surface, a crucial condition for wet adhesion mediated by capillary forces. Instead, these flies walk solely on their claws. Moreover, we were able to show that the mutation is caused by a P-element insertion into the Su(z)2 gene locus. Remobilization of the P-element restores climbing ability. Furthermore, we provide evidence that the P-element insertion results in an artificial Su(z)2 transcript, which most likely causes a gain-of-function mutation. We presume that this transcript causes deregulation of yet unknown target genes involved in pulvilli differentiation. Our results nicely demonstrate that the genetically treatable model organism Drosophila is highly suitable for future investigations on adhesive organ differentiation. © 2015. Published by The Company of Biologists Ltd.

Differential DNA methylation at conserved non-genic elements and evidence for transgenerational inheritance following developmental exposure to mono(2-ethylhexyl) phthalate and 5-azacytidine in zebrafish.

PubMed

Kamstra, Jorke H; Sales, Liana Bastos; Aleström, Peter; Legler, Juliette

2017-01-01

Exposure to environmental stressors during development may lead to latent and transgenerational adverse health effects. To understand the role of DNA methylation in these effects, we used zebrafish as a vertebrate model to investigate heritable changes in DNA methylation following chemical-induced stress during early development. We exposed zebrafish embryos to non-embryotoxic concentrations of the biologically active phthalate metabolite mono(2-ethylhexyl) phthalate (MEHP, 30 µM) and the DNA methyltransferase 1 inhibitor 5-azacytidine (5AC, 10 µM). Direct, latent and transgenerational effects on DNA methylation were assessed using global, genome-wide and locus-specific DNA methylation analyses. Following direct exposure in zebrafish embryos from 0 to 6 days post-fertilization, genome-wide analysis revealed a multitude of differentially methylated regions, strongly enriched at conserved non-genic elements for both compounds. Pathways involved in adipogenesis were enriched with the putative obesogenic compound MEHP. Exposure to 5AC resulted in enrichment of pathways involved in embryonic development and transgenerational effects on larval body length. Locus-specific methylation analysis of 10 differentially methylated sites revealed six of these loci differentially methylated in sperm sampled from adult zebrafish exposed during development to 5AC, and in first and second generation larvae. With MEHP, consistent changes were found at 2 specific loci in first and second generation larvae. Our results suggest a functional role for DNA methylation on cis-regulatory conserved elements following developmental exposure to compounds. Effects on these regions are potentially transferred to subsequent generations.

Epigenetic Differentiation of Natural Populations of Lilium bosniacum Associated with Contrasting Habitat Conditions.

PubMed

Zoldoš, Vlatka; Biruš, Ivan; Muratovic, Edina; Šatovic, Zlatko; Vojta, Aleksandar; Robin, Odile; Pustahija, Fatima; Bogunic, Faruk; Vicic Bockor, Vedrana; Siljak-Yakovlev, Sonja

2018-01-01

Epigenetic variation in natural populations with contrasting habitats might be an important element, in addition to the genetic variation, in plant adaptation to environmental stress. Here, we assessed genetic, epigenetic, and cytogenetic structure of the three Lilium bosniacum populations growing on distinct habitats. One population was growing under habitual ecological conditions for this species and the other two were growing under stress associated with high altitude and serpentine soil. Amplified fragment length polymorphism and methylation-sensitive amplification polymorphism analyses revealed that the three populations did not differentiate genetically, but were clearly separated in three distinct clusters according to DNA methylation profiles. Principal coordinate analysis showed that overall epigenetic variation was closely related to habitat conditions. A new methylation-sensitive amplification polymorphism scoring approach allowed identification of mainly unmethylated (φST = 0.190) and fully CpG methylated (φST = 0.118) subepiloci playing a role in overall population differentiation, in comparison with hemimethylated sites (φST = 0.073). In addition, unusual rDNA repatterning and the presence of B chromosomes bearing 5S rDNA loci were recorded in the population growing on serpentine soil, suggesting dynamic chromosome rearrangements probably linked to global genome demethylation, which might have reactivated some mobile elements. We discuss our results considering our earlier data on morphology and leaf anatomy of several L. bosniacum populations, and suggest a possible role of epigenetics as a key element in population differentiation associated with environmental stress in these particular lily populations. © The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

The method of averages applied to the KS differential equations

NASA Technical Reports Server (NTRS)

Graf, O. F., Jr.; Mueller, A. C.; Starke, S. E.

1977-01-01

A new approach for the solution of artificial satellite trajectory problems is proposed. The basic idea is to apply an analytical solution method (the method of averages) to an appropriate formulation of the orbital mechanics equations of motion (the KS-element differential equations). The result is a set of transformed equations of motion that are more amenable to numerical solution.

Integrated Information and State Differentiation

PubMed Central

Marshall, William; Gomez-Ramirez, Jaime; Tononi, Giulio

2016-01-01

Integrated information (Φ) is a measure of the cause-effect power of a physical system. This paper investigates the relationship between Φ as defined in Integrated Information Theory and state differentiation (D), the number of, and difference between potential system states. Here we provide theoretical justification of the relationship between Φ and D, then validate the results using a simulation study. First, we show that a physical system in a state with high Φ necessarily has many elements and specifies many causal relationships. Furthermore, if the average value of integrated information across all states is high, the system must also have high differentiation. Next, we explore the use of D as a proxy for Φ using artificial networks, evolved to have integrated structures. The results show a positive linear relationship between Φ and D for multiple network sizes and connectivity patterns. Finally we investigate the differentiation evoked by sensory inputs and show that, under certain conditions, it is possible to estimate integrated information without a direct perturbation of its internal elements. In concluding, we discuss the need for further validation on larger networks and explore the potential applications of this work to the empirical study of consciousness, especially concerning the practical estimation of Φ from neuroimaging data. PMID:27445896

Identification of species of the Euterpe genus by rare earth elements using inductively coupled plasma mass spectrometry and linear discriminant analysis.

PubMed

Santos, Vívian Silva; Nardini, Viviani; Cunha, Luís Carlos; Barbosa, Fernando; De Almeida Teixeira, Gustavo Henrique

2014-06-15

The açaí (Euterpe oleracea Mart.) and juçara (Euterpe edulis Mart.) produce similar fruits which are rich in energy, minerals, vitamins and natural compounds with antioxidant and anti-inflammatory properties. Although the drink obtained from these species is similar, it is important to develop tools to establish the identity of the fruit species and growing regions. To assess claims of origin and for other purposes, we use multivariate analysis to investigate the differentiation of açaí and juçara fruits based on rare earth element (REE) content determined by Inductively Coupled Plasma Mass Spectrometry. REE content, in particular Sm, Th, La, Pr, Gd, and especially Ce and Nd varied between species. PCA analysis was not efficient in differentiating açaí from juçara fruit samples. In contrast, LDA analysis permitted a correct differentiation between species with a predictive ability of 83.3%. The methodology that we have applied confirms that REE can be used to differentiate between açaí and juçara fruit samples and to identify their origin. Copyright © 2013 Elsevier Ltd. All rights reserved.

Modelling of Equilibrium Between Mantle and Core: Refractory, Volatile, and Highly Siderophile Elements

NASA Technical Reports Server (NTRS)

Righter, K.; Danielson, L.; Pando, K.; Shofner, G.; Lee, C. -T.

2013-01-01

Siderophile elements have been used to constrain conditions of core formation and differentiation for the Earth, Mars and other differentiated bodies [1]. Recent models for the Earth have concluded that the mantle and core did not fully equilibrate and the siderophile element contents of the mantle can only be explained under conditions where the oxygen fugacity changes from low to high during accretion and the mantle and core do not fully equilibrate [2,3]. However these conclusions go against several physical and chemical constraints. First, calculations suggest that even with the composition of accreting material changing from reduced to oxidized over time, the fO2 defined by metal-silicate equilibrium does not change substantially, only by approximately 1 logfO2 unit [4]. An increase of more than 2 logfO2 units in mantle oxidation are required in models of [2,3]. Secondly, calculations also show that metallic impacting material will become deformed and sheared during accretion to a large body, such that it becomes emulsified to a fine scale that allows equilibrium at nearly all conditions except for possibly the length scale for giant impacts [5] (contrary to conclusions of [6]). Using new data for D(Mo) metal/silicate at high pressures, together with updated partitioning expressions for many other elements, we will show that metal-silicate equilibrium across a long span of Earth s accretion history may explain the concentrations of many siderophile elements in Earth's mantle. The modeling includes refractory elements Ni, Co, Mo, and W, as well as highly siderophile elements Au, Pd and Pt, and volatile elements Cd, In, Bi, Sb, Ge and As.

A new method for constructing analytic elements for groundwater flow.

NASA Astrophysics Data System (ADS)

Strack, O. D.

2007-12-01

The analytic element method is based upon the superposition of analytic functions that are defined throughout the infinite domain, and can be used to meet a variety of boundary conditions. Analytic elements have been use successfully for a number of problems, mainly dealing with the Poisson equation (see, e.g., Theory and Applications of the Analytic Element Method, Reviews of Geophysics, 41,2/1005 2003 by O.D.L. Strack). The majority of these analytic elements consists of functions that exhibit jumps along lines or curves. Such linear analytic elements have been developed also for other partial differential equations, e.g., the modified Helmholz equation and the heat equation, and were constructed by integrating elementary solutions, the point sink and the point doublet, along a line. This approach is limiting for two reasons. First, the existence is required of the elementary solutions, and, second, the integration tends to limit the range of solutions that can be obtained. We present a procedure for generating analytic elements that requires merely the existence of a harmonic function with the desired properties; such functions exist in abundance. The procedure to be presented is used to generalize this harmonic function in such a way that the resulting expression satisfies the applicable differential equation. The approach will be applied, along with numerical examples, for the modified Helmholz equation and for the heat equation, while it is noted that the method is in no way restricted to these equations. The procedure is carried out entirely in terms of complex variables, using Wirtinger calculus.