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Sample records for activation occurs early

  1. Naturally Occurring Changes in Time Spent Watching Television Are Inversely Related to Frequency of Physical Activity during Early Adolescence

    ERIC Educational Resources Information Center

    Motl, Robert W.; McAuley, Edward; Birnbaum, Amanda S.; Lytle, Leslie A.

    2006-01-01

    In this longitudinal study, we examined the relationship between changes in time spent watching television and playing video games with frequency of leisure-time physical activity across a 2-year period among adolescent boys and girls (N=4594). Latent growth modelling indicated that a decrease in time spent watching television was associated with…

  2. Sympathetic sprouting near sensory neurons after nerve injury occurs preferentially on spontaneously active cells and is reduced by early nerve block

    PubMed Central

    Xie, Wenrui; Strong, Judith Ann; Li, Huiqing; Zhang, Jun-Ming

    2006-01-01

    Some chronic pain conditions are maintained or enhanced by sympathetic activity. In animal models of pathological pain, abnormal sprouting of sympathetic fibers around large- and medium-size sensory neurons is observed in dorsal root ganglia (DRG). Large and medium size cells are also more likely to be spontaneously active, suggesting that sprouting may be related to neuron activity. We previously showed that sprouting could be reduced by systemic or locally applied lidocaine. In the complete sciatic nerve transection model in rats, spontaneous activity initially originates in the injury site; later, the DRG become the major source of spontaneous activity. In this study, spontaneous activity reaching the DRG soma was reduced by early nerve blockade (local perfusion of the transected nerve with TTX for the first 7 days after injury). This significantly reduced sympathetic sprouting. Conversely, increasing spontaneous activity by local nerve perfusion with K+ channel blockers increased sprouting. The hyperexcitability and spontaneous activity of DRG neurons observed in this model were also significantly reduced by early nerve blockade. These effects of early nerve blockade on sprouting, excitability, and spontaneous activity were all observed 4 to 5 weeks after the end of early nerve blockade, indicating that the early period of spontaneous activity in the injured nerve is critical for establishing the more long-lasting pathologies observed in the DRG. Individual spontaneously active neurons, labeled with fluorescent dye, were 5–6 times more likely than quiescent cells to be co-localized with sympathetic fibers, suggesting a highly localized correlation of activity and sprouting. PMID:17065247

  3. Estrogenic activity of naturally occurring anthocyanidins.

    PubMed

    Schmitt, E; Stopper, H

    2001-01-01

    Anthocyanins, which are natural plant pigments from the flavonoid family, represent substantial constituents of the human diet. Because some other bioflavonoids are known to have estrogenic activity, the aim of this study was to determine the estrogenic activity of the anthocyanine aglycones. Binding affinity to the estrogen receptor-alpha was 10,000- to 20,000-fold lower than that of the endogenous estrogen estradiol. In the estrogen receptor-positive cell line MCF-7, the anthocyanidins induced expression of a reporter gene. The tested anthocyanidins showed estrogen-inducible cell proliferation in two cell lines (MCF-7 and BG-1), but not in the receptor-negative human breast cancer cell line MDA-MB-231. The phytoestrogen-induced cell proliferation could be blocked by addition of the receptor antagonist 4-hydroxytamoxifen. Combination treatments with the endogenous estrogen estradiol resulted in a reduction of estradiol-induced cell proliferation. Overall, the tested anthocyanidins exert estrogenic activity, which might play a role in altering the development of hormone-dependent adverse effects.

  4. Naturally occurring cobalamins have antimalarial activity.

    PubMed

    Chemaly, Susan M; Chen, Chien-Teng; van Zyl, Robyn L

    2007-05-01

    The acquisition of resistance by malaria parasites towards existing antimalarials has necessitated the development of new chemotherapeutic agents. The effect of vitamin B(12) derivatives on the formation of beta-haematin (synthetic haemozoin) was determined under conditions similar to those in the parasitic food vacuole (using chloroquine, a known inhibitor of haemozoin formation for comparison). Adenosylcobalamin (Ado-cbl), methylcobalamin (CH(3)-cbl) and aquocobalamin (H(2)O-cbl) were approximately forty times more effective inhibitors of beta-haematin formation than chloroquine, cyanocobalamin (CN-cbl) was slightly more inhibitory than chloroquine, while dicyanocobinamide had no effect. It is proposed that the cobalamins exert their inhibitory effect on beta-haematin formation by pi-interactions of their corrin ring with the Fe(III)-protoporphyrin ring and by hydrogen-bonding using their 5,6-dimethylbenzimidazole/ribose/sugar side-chain. The antimalarial activity for the cobalamins (Ado-cbl>CH(3)-cbl>H(2)O-cbl>CN-cbl) was found to be less than that for chloroquine or quinine. Ado-cbl, CH(3)-cbl and CN-cbl do not accumulate in the parasite food vacuole by pH trapping, but H(2)O-cbl does. Unlike humans, the malaria parasite has only one enzyme that uses cobalamin as a cofactor, namely methionine synthase, which is important for growth and metabolism. Thus cobalamins in very small amounts are necessary for Plasmodium falciparum growth but in larger amounts they display antimalarial properties. PMID:17343914

  5. Loss of primary cilia occurs early in breast cancer development

    PubMed Central

    2014-01-01

    Background Primary cilia are microtubule-based organelles that protrude from the cell surface. Primary cilia play a critical role in development and disease through regulation of signaling pathways including the Hedgehog pathway. Recent mouse models have also linked ciliary dysfunction to cancer. However, little is known about the role of primary cilia in breast cancer development. Primary cilia expression was characterized in cancer cells as well as their surrounding stromal cells from 86 breast cancer patients by counting cilia and measuring cilia length. In addition, we examined cilia expression in normal epithelial and stromal cells from reduction mammoplasties as well as histologically normal adjacent tissue for comparison. Results We observed a statistically significant decrease in the percentage of ciliated cells on both premalignant lesions as well as in invasive cancers. This loss of cilia does not correlate with increased proliferative index (Ki67-positive cells). However, we did detect rare ciliated cancer cells present in patients with invasive breast cancer and found that these express a marker of basaloid cancers that is associated with poor prognosis (Cytokeratin 5). Interestingly, the percentage of ciliated stromal cells associated with both premalignant and invasive cancers decreased when compared to stromal cells associated with normal tissue. To understand how cilia may be lost during cancer development we analyzed the expression of genes required for ciliogenesis and/or ciliary function and compared their expression in normal versus breast cancer samples. We found that expression of ciliary genes were frequently downregulated in human breast cancers. Conclusions These data suggest that primary cilia are lost early in breast cancer development on both the cancer cells and their surrounding stromal cells. PMID:24987519

  6. 32 CFR 716.6 - Death occurring after active service.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 5 2014-07-01 2014-07-01 false Death occurring after active service. 716.6 Section 716.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after...

  7. 32 CFR 716.6 - Death occurring after active service.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 5 2011-07-01 2011-07-01 false Death occurring after active service. 716.6 Section 716.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after...

  8. 32 CFR 716.6 - Death occurring after active service.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 5 2012-07-01 2012-07-01 false Death occurring after active service. 716.6 Section 716.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after...

  9. 32 CFR 716.6 - Death occurring after active service.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 5 2013-07-01 2013-07-01 false Death occurring after active service. 716.6 Section 716.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after...

  10. 32 CFR 716.6 - Death occurring after active service.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 5 2010-07-01 2010-07-01 false Death occurring after active service. 716.6 Section 716.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after...

  11. Conscious processing during retrieval can occur in early and late visual regions.

    PubMed

    Thakral, Preston P; Slotnick, Scott D; Schacter, Daniel L

    2013-02-01

    Previous evidence has suggested a functional-anatomic dissociation between conscious and nonconscious processing during retrieval where early visual regions BA17/18 are associated with nonconscious processing and late visual regions BA19/37 are associated with conscious processing. However, evidence for this dissociation has only been observed using a limited number of experimental paradigms. In the present functional magnetic resonance imaging (fMRI) study, we tested the hypothesis that conscious processing during retrieval can occur in BA17/18 using memorial paradigms that recruited processing in these early visual regions. During the encoding phase of Experiment 1, abstract shapes with colored and oriented internal lines were presented to the left and right of fixation. During the retrieval phase, old shapes and new shapes were presented at fixation and participants classified each item as "old-left", "old-right", or "new". The contrast of spatial memory-hits>spatial memory-misses (with accurate item memory) produced activity in BA17/18. During the encoding phase of Experiment 2, abstract shapes with colored and oriented internal lines were presented at fixation. During the retrieval phase, old shapes, changed shapes (with the same outline but different colored and oriented internal lines), and new shapes were presented at fixation and participants made an old-new classification during runs with a specific retrieval orientation or a non-specific retrieval orientation. Critically, the contrast of old-hits>old-misses during specific retrieval orientation produced activity in BA17/18. The results of the present experiments support the hypothesis that conscious processing during retrieval can occur in BA17/18.

  12. An Update on Antitumor Activity of Naturally Occurring Chalcones

    PubMed Central

    Zhang, En-Hui; Wang, Ru-Feng; Guo, Shu-Zhen; Liu, Bin

    2013-01-01

    Chalcones, which have characteristic 1,3-diaryl-2-propen-1-one skeleton, are mainly produced in roots, rhizomes, heartwood, leaves, and seeds of genera Angelica, Sophora, Glycyrrhiza, Humulus, Scutellaria, Parartocarpus, Ficus, Dorstenia, Morus, Artocarpus, and so forth. They have become of interest in the research and development of natural antitumor agents over the past decades due to their broad range of mechanisms including anti-initiation, induction of apoptosis, antiproliferation, antimetastasis, antiangiogenesis, and so forth. This review summarizes the studies on the antitumor activity of naturally occurring chalcones and their underlying mechanisms in detail during the past decades. PMID:23690855

  13. Synthetic muscle promoters: activities exceeding naturally occurring regulatory sequences

    NASA Technical Reports Server (NTRS)

    Li, X.; Eastman, E. M.; Schwartz, R. J.; Draghia-Akli, R.

    1999-01-01

    Relatively low levels of expression from naturally occurring promoters have limited the use of muscle as a gene therapy target. Myogenic restricted gene promoters display complex organization usually involving combinations of several myogenic regulatory elements. By random assembly of E-box, MEF-2, TEF-1, and SRE sites into synthetic promoter recombinant libraries, and screening of hundreds of individual clones for transcriptional activity in vitro and in vivo, several artificial promoters were isolated whose transcriptional potencies greatly exceed those of natural myogenic and viral gene promoters.

  14. An update on antitumor activity of naturally occurring chalcones.

    PubMed

    Zhang, En-Hui; Wang, Ru-Feng; Guo, Shu-Zhen; Liu, Bin

    2013-01-01

    Chalcones, which have characteristic 1,3-diaryl-2-propen-1-one skeleton, are mainly produced in roots, rhizomes, heartwood, leaves, and seeds of genera Angelica, Sophora, Glycyrrhiza, Humulus, Scutellaria, Parartocarpus, Ficus, Dorstenia, Morus, Artocarpus, and so forth. They have become of interest in the research and development of natural antitumor agents over the past decades due to their broad range of mechanisms including anti-initiation, induction of apoptosis, antiproliferation, antimetastasis, antiangiogenesis, and so forth. This review summarizes the studies on the antitumor activity of naturally occurring chalcones and their underlying mechanisms in detail during the past decades.

  15. Amplification of the 20q Chromosomal Arm Occurs Early in Tumorigenic Transformation and May Initiate Cancer

    PubMed Central

    Buganim, Yosef; Solomon, Hilla; Goldfinger, Naomi; Hovland, Randi; Ke, Xi-Song; Oyan, Anne M.; Kalland, Karl-H.; Rotter, Varda; Domany, Eytan

    2011-01-01

    Duplication of chromosomal arm 20q occurs in prostate, cervical, colon, gastric, bladder, melanoma, pancreas and breast cancer, suggesting that 20q amplification may play a causal role in tumorigenesis. According to an alternative view, chromosomal imbalance is mainly a common side effect of cancer progression. To test whether a specific genomic aberration might serve as a cancer initiating event, we established an in vitro system that models the evolutionary process of early stages of prostate tumor formation; normal prostate cells were immortalized by the over-expression of human telomerase catalytic subunit hTERT, and cultured for 650 days till several transformation hallmarks were observed. Gene expression patterns were measured and chromosomal aberrations were monitored by spectral karyotype analysis at different times. Several chromosomal aberrations, in particular duplication of chromosomal arm 20q, occurred early in the process and were fixed in the cell populations, while other aberrations became extinct shortly after their appearance. A wide range of bioinformatic tools, applied to our data and to data from several cancer databases, revealed that spontaneous 20q amplification can promote cancer initiation. Our computational model suggests that 20q amplification induced deregulation of several specific cancer-related pathways including the MAPK pathway, the p53 pathway and Polycomb group factors. In addition, activation of Myc, AML, B-Catenin and the ETS family transcription factors was identified as an important step in cancer development driven by 20q amplification. Finally we identified 13 "cancer initiating genes", located on 20q13, which were significantly over-expressed in many tumors, with expression levels correlated with tumor grade and outcome suggesting that these genes induce the malignant process upon 20q amplification. PMID:21297939

  16. Early inflammatory damage to intestinal neurons occurs via inducible nitric oxide synthase.

    PubMed

    Venkataramana, Shriram; Lourenssen, S; Miller, K G; Blennerhassett, M G

    2015-03-01

    Intestinal inflammation affects the enteric nervous system (ENS) that lies adjacent to the smooth muscle layers. Previously, we showed that the loss of ENS neurons in animal models such as tri-nitrobenzene sulphonic acid (TNBS)-induced colitis was a limited and early event despite progressive worsening of inflammation. Here, we demonstrated that the rapid appearance of activated immune cells in the intestinal wall is selectively neurotoxic via iNOS-derived NO, using TNBS-induced colitis in both rats and mice, and a co-culture model of ENS neurons and smooth muscle. An influx of neutrophils and macrophages occurred within hours of initiation of rat colitis, correlating with iNOS expression, acutely elevated NO and neuronal death. In vitro, chemical donors of NO selectively caused axonal damage and neuronal death. These outcomes were similar to those seen with combined culture with either activated peritoneal immune cells or the immune cell lines RAW-264 and RBL-2H3. Immune cell-mediated neurotoxicity was blocked by the iNOS inhibitor L-NIL, and neuronal death was inhibited by the RIP-1 kinase inhibitor necrostatin. In a mouse model, the stereotypic loss of myenteric neurons by Day 4 post-TNBS was abrogated by the selective iNOS inhibitors L-NIL or 1400W without effect on other parameters of intestinal inflammation. Preservation of ENS neurons also ameliorated the hyperplasia of smooth muscle that is characteristic of intestinal inflammation, in line with prior work showing neural regulation of smooth muscle phenotype. This identifies a predominant pathway of immune cell damage to the ENS, where early, acute elevation of NO from iNOS can be cytotoxic to myenteric neurons.

  17. Identification of Telomerase-activating Blends From Naturally Occurring Compounds.

    PubMed

    Ait-Ghezala, Ghania; Hassan, Samira; Tweed, Miles; Paris, Daniel; Crynen, Gogce; Zakirova, Zuchra; Crynen, Stefan; Crawford, Fiona

    2016-06-01

    telomerase activity, and combinations of the top-ranking compounds were able to increase telomerase activity significantly, from 51% to 290%, relative to controls. Conclusions • The results have confirmed that many naturally occurring compounds hold the potential to activate telomerase and that certain of those compounds have demonstrated synergistic effects to produce more potent blends. Given the relationship between telomere shortening, aging, and the decline of tissue function, it is reasonable to hypothesize that such telomerase-activating blends may have health-promoting benefits, particularly in relation to aging-associated conditions. Further investigation of such blends in human studies that are designed to evaluate safety and the effects on telomere length are thus warranted.

  18. Identification of Telomerase-activating Blends From Naturally Occurring Compounds.

    PubMed

    Ait-Ghezala, Ghania; Hassan, Samira; Tweed, Miles; Paris, Daniel; Crynen, Gogce; Zakirova, Zuchra; Crynen, Stefan; Crawford, Fiona

    2016-06-01

    telomerase activity, and combinations of the top-ranking compounds were able to increase telomerase activity significantly, from 51% to 290%, relative to controls. Conclusions • The results have confirmed that many naturally occurring compounds hold the potential to activate telomerase and that certain of those compounds have demonstrated synergistic effects to produce more potent blends. Given the relationship between telomere shortening, aging, and the decline of tissue function, it is reasonable to hypothesize that such telomerase-activating blends may have health-promoting benefits, particularly in relation to aging-associated conditions. Further investigation of such blends in human studies that are designed to evaluate safety and the effects on telomere length are thus warranted. PMID:27433836

  19. Active experiments, magnetospheric modification, and a naturally occurring analogue

    NASA Technical Reports Server (NTRS)

    Kivelson, M. G.; Russell, C. T.

    1973-01-01

    Recently, a scheme has been proposed which would modify the magnetosphere by injecting plasma near the equator beyond the plasmapause and initiating wave-particle instabilities. The expected effects have been examined theoretically. Injection of plasma into this region is also a naturally occurring phenomenon produced by the cross-tail electric fields which are associated with geomagnetic activity. For further investigation of magnetospheric instabilities, the advantages of examining artificially injected plasma (control of time and location of injection and of the volume of plasma injected) contrast with the advantages of studying natural enhancements (no extra payload, frequent occurrence). Thus, the two types of experiments are complementary. In preliminary studies of natural plasma enhancements both ULF and ELF emissions have been observed. The ELF noise is consistent with generation by the electron cyclotron instability.

  20. Widespread somatic L1 retrotransposition occurs early during gastrointestinal cancer evolution

    PubMed Central

    Ewing, Adam D.; Gacita, Anthony; Wood, Laura D.; Ma, Florence; Xing, Dongmei; Kim, Min-Sik; Manda, Srikanth S.; Abril, Gabriela; Pereira, Gavin; Makohon-Moore, Alvin; Looijenga, Leendert H.J.; Gillis, Ad J.M.; Hruban, Ralph H.; Anders, Robert A.; Romans, Katharine E.; Pandey, Akhilesh; Iacobuzio-Donahue, Christine A.; Vogelstein, Bert; Kinzler, Kenneth W.; Kazazian, Haig H.; Solyom, Szilvia

    2015-01-01

    Somatic L1 retrotransposition events have been shown to occur in epithelial cancers. Here, we attempted to determine how early somatic L1 insertions occurred during the development of gastrointestinal (GI) cancers. Using L1-targeted resequencing (L1-seq), we studied different stages of four colorectal cancers arising from colonic polyps, seven pancreatic carcinomas, as well as seven gastric cancers. Surprisingly, we found somatic L1 insertions not only in all cancer types and metastases but also in colonic adenomas, well-known cancer precursors. Some insertions were also present in low quantities in normal GI tissues, occasionally caught in the act of being clonally fixed in the adjacent tumors. Insertions in adenomas and cancers numbered in the hundreds, and many were present in multiple tumor sections, implying clonal distribution. Our results demonstrate that extensive somatic insertional mutagenesis occurs very early during the development of GI tumors, probably before dysplastic growth. PMID:26260970

  1. Selection occurs within linear fruit and during the early stages of reproduction in Robinia pseudoacacia

    PubMed Central

    2014-01-01

    Background Pollen donor compositions differ during the early stages of reproduction due to various selection mechanisms. In addition, ovules linearly ordered within a fruit have different probabilities of reaching maturity. Few attempts, however, have been made to directly examine the magnitude and timing of selection, as well as the mechanisms during early life stages and within fruit. Robinia pseudoacacia, which contains linear fruit and non-random ovule maturation and abortion patterns, has been used to study the viability of selection within fruit and during the early stages of reproduction. To examine changes in the pollen donor composition during the early stages of reproduction and of progeny originating from different positions within fruit, paternity analyses were performed for three early life stages (aborted seeds, mature seeds and seedlings) in the insect-pollinated tree R. pseudoacacia. Results Selection resulted in an overall decrease in the level of surviving selfed progeny at each life stage. The greatest change was observed between the aborted seed stage and mature seed stage, indicative of inbreeding depression (the reduced fitness of a given population that occurs when related individual breeding was responsible for early selection). A selective advantage was detected among paternal trees. Within fruits, the distal ends showed higher outcrossing rates than the basal ends, indicative of selection based on the order of seeds within the fruit. Conclusions Our results suggest that selection exists both within linear fruit and during the early stages of reproduction, and that this selection can affect male reproductive success during the early life stages. This indicates that tree species with mixed-mating systems may have evolved pollen selection mechanisms to increase the fitness of progeny and adjust the population genetic composition. The early selection that we detected suggests that inbreeding depression caused the high abortion rate and low

  2. Antituberculosis Activity of a Naturally Occurring Flavonoid, Isorhamnetin.

    PubMed

    Jnawali, Hum Nath; Jeon, Dasom; Jeong, Min-Cheol; Lee, Eunjung; Jin, Bongwhan; Ryoo, Sungweon; Yoo, Jungheon; Jung, In Duk; Lee, Seung Jun; Park, Yeong-Min; Kim, Yangmee

    2016-04-22

    Isorhamnetin (1) is a naturally occurring flavonoid having anticancer and anti-inflammatory properties. The present study demonstrated that 1 had antimycobacterial effects on Mycobacterium tuberculosis H37Rv, multi-drug- and extensively drug-resistant clinical isolates with minimum inhibitory concentrations of 158 and 316 μM, respectively. Mycobacteria mainly affect the lungs, causing an intense local inflammatory response that is critical to the pathogenesis of tuberculosis. We investigated the effects of 1 on interferon (IFN)-γ-stimulated human lung fibroblast MRC-5 cells. Isorhamnetin suppressed the release of tumor necrosis factor (TNF)-α and interleukin (IL)-12. A nontoxic dose of 1 reduced mRNA expression of TNF-α, IL-1β, IL-6, IL-12, and matrix metalloproteinase-1 in IFN-γ-stimulated cells. Isorhamnetin inhibited IFN-γ-mediated stimulation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase and showed high-affinity binding to these kinases (binding constants: 4.46 × 10(6) M(-1) and 7.6 × 10(6) M(-1), respectively). The 4'-hydroxy group and the 3'-methoxy group of the B-ring and the 5-hydroxy group of the A-ring of 1 play key roles in these binding interactions. A mouse in vivo study of lipopolysaccharide-induced lung inflammation revealed that a nontoxic dose of 1 reduced the levels of IL-1β, IL-6, IL-12, and INF-γ in lung tissue. These data provide the first evidence that 1 could be developed as a potent antituberculosis drug. PMID:26974691

  3. 33 CFR 330.3 - Activities occurring before certain dates.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... waters of the United States outside the limits of navigable waters of the United States that occurred before the phase-in dates which extended Section 404 jurisdiction to all waters of the United States. The phase-in dates were: After July 25, 1975, discharges into navigable waters......

  4. 33 CFR 330.3 - Activities occurring before certain dates.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... waters of the United States outside the limits of navigable waters of the United States that occurred before the phase-in dates which extended Section 404 jurisdiction to all waters of the United States. The phase-in dates were: After July 25, 1975, discharges into navigable waters......

  5. 33 CFR 330.3 - Activities occurring before certain dates.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... waters of the United States outside the limits of navigable waters of the United States that occurred before the phase-in dates which extended Section 404 jurisdiction to all waters of the United States. The phase-in dates were: After July 25, 1975, discharges into navigable waters......

  6. 33 CFR 330.3 - Activities occurring before certain dates.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... waters of the United States outside the limits of navigable waters of the United States that occurred before the phase-in dates which extended Section 404 jurisdiction to all waters of the United States. The phase-in dates were: After July 25, 1975, discharges into navigable waters......

  7. Facile synthesis and antibacterial activity of naturally occurring 5-methoxyfuroflavone.

    PubMed

    Alam, Mohammad Sayed; Lee, Dong-Ung

    2010-12-01

    A convenient synthesis of 5-methoxyfuroflavone (6, pongaglabol methyl ether), a constituent of some Pongamia or Millettia genus, was achieved by starting from 2,4-dihydroxy-6-methoxyacetophenone via a chalcone precursor, followed by treatment with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). This five-step reaction (total yield: 21.6%) is more facile with that of previously utilized procedures using each different starting material. Antibacterial activities of the above compound and its precursor chalcones, which also belongs to the class of furoflavonoids, were tested by the disc diffusion method against Shigella dysenteriae, Salmonella typhi, Streptococcus-β-haemolyticus, and Staphylococcus aureus. 5-Methoxyfuroflavone showed moderate bactericidal activity against all tested bacterial strains, whereas its corresponding chalcone compound revealed a selective activity. PMID:21139271

  8. Choctaw Culture Early Education Activities.

    ERIC Educational Resources Information Center

    Brescia, William, Ed.; Reeves, Carolyn, Ed.; Skinner, Linda, Ed.

    An effort to better prepare Choctaw youngsters for kindergarten, the Choctaw Culture Early Education Program developed a resource of 58 activities adapted to meet the needs of Choctaw 3- and 4-year olds. The activities are divided into four sections pertaining to getting started, relating to five project publications (How the Flowers Came to Be,…

  9. Potentiation of concentric force and acceleration only occurs early during the stretch-shortening cycle.

    PubMed

    McCarthy, John P; Wood, David S; Bolding, Mark S; Roy, Jane L P; Hunter, Gary R

    2012-09-01

    The purpose of this study was to determine where stretch-shortening cycle (SSC) potentiation of force, power, velocity, and acceleration occurs across the concentric phase of ballistic leg presses. Second, we examined the influence of late eccentric phase force and length of the amortization phase on potentiated concentric phase performance variables. Twenty-one male runners (age: 31.9 ± 4.7 years) performed SSC and concentric-only (CO) ballistic leg press throws. Potentiations of concentric actions were calculated as the difference between SSC and CO contractions. An analysis splitting the concentric range of motion (ROM) into 6 equal time intervals determined force and acceleration were potentiated (p < 0.05) only during the first one-sixth time interval of concentric motion, whereas velocity and power were potentiated (p < 0.05) at all time intervals over the entire concentric motion with the exception of power over the last one-sixth time interval. A more precise analysis examining 20-millisecond time intervals across the first 200 milliseconds of concentric motion determined force was potentiated only over the first 140 milliseconds and acceleration only over the first 160 milliseconds. Eccentric force measured during the last 100 milliseconds of eccentric motion was related to potentiated force during the initial 200 milliseconds of concentric motion (r = 0.44, p < 0.05) and potentiated mean power across the full concentric ROM (r = 0.62, p < 0.01). Results indicate that in contrast to power and velocity, potentiation of force and acceleration occurs only early during the concentric phase of SSC ballistic leg presses. Correlational findings imply late eccentric phase force is important for generating force and power during the concentric phase of the SSC and thus training focusing on enhancing late phase eccentric force appears important for developing explosive force and power during SSC movements. PMID:22692115

  10. Potentiation of concentric force and acceleration only occurs early during the stretch-shortening cycle.

    PubMed

    McCarthy, John P; Wood, David S; Bolding, Mark S; Roy, Jane L P; Hunter, Gary R

    2012-09-01

    The purpose of this study was to determine where stretch-shortening cycle (SSC) potentiation of force, power, velocity, and acceleration occurs across the concentric phase of ballistic leg presses. Second, we examined the influence of late eccentric phase force and length of the amortization phase on potentiated concentric phase performance variables. Twenty-one male runners (age: 31.9 ± 4.7 years) performed SSC and concentric-only (CO) ballistic leg press throws. Potentiations of concentric actions were calculated as the difference between SSC and CO contractions. An analysis splitting the concentric range of motion (ROM) into 6 equal time intervals determined force and acceleration were potentiated (p < 0.05) only during the first one-sixth time interval of concentric motion, whereas velocity and power were potentiated (p < 0.05) at all time intervals over the entire concentric motion with the exception of power over the last one-sixth time interval. A more precise analysis examining 20-millisecond time intervals across the first 200 milliseconds of concentric motion determined force was potentiated only over the first 140 milliseconds and acceleration only over the first 160 milliseconds. Eccentric force measured during the last 100 milliseconds of eccentric motion was related to potentiated force during the initial 200 milliseconds of concentric motion (r = 0.44, p < 0.05) and potentiated mean power across the full concentric ROM (r = 0.62, p < 0.01). Results indicate that in contrast to power and velocity, potentiation of force and acceleration occurs only early during the concentric phase of SSC ballistic leg presses. Correlational findings imply late eccentric phase force is important for generating force and power during the concentric phase of the SSC and thus training focusing on enhancing late phase eccentric force appears important for developing explosive force and power during SSC movements.

  11. Delayed perforation occurring after endoscopic submucosal dissection for early gastric cancer.

    PubMed

    Ikezawa, Kenji; Michida, Tomoki; Iwahashi, Kiyoshi; Maeda, Kosaku; Naito, Masafumi; Ito, Toshifumi; Katayama, Kazuhiro

    2012-01-01

    Delayed perforation occurring after endoscopic submucosal dissection (ESD) is a rare but serious complication which sometimes requires emergent surgery. However, reports of its characteristics, including endoscopic imaging and management, are not fully detailed. A 70-year-old woman was referred to our hospital for the treatment of early gastric cancer. On the day of the ESD, hematemesis was observed because of a Mallory-Weiss tear, and a visible vessel in the post-ESD ulcer was additionally treated endoscopically by coagulation. Second-look endoscopic examination on the next day revealed a perforation 3 mm in diameter at the treated vessel in the ulcer. The shape of the perforation was round and the color of the surrounding muscle layer had become whitish. The perforation was closed with endoclips, and decompression of the pneumoperitoneum was performed. The patient was conservatively managed and was discharged 13 days after the ESD. We show endoscopic images of delayed perforation and discuss the mechanism and management of this complication.

  12. Early detection of hepatocellular carcinoma co-occurring with hepatitis C virus infection: A mathematical model

    PubMed Central

    Zekri, Abdel-Rahman Nabawy; Youssef, Amira Salah El-Din; Bakr, Yasser Mabrouk; Gabr, Reham Mohamed; Ahmed, Ola Sayed; Elberry, Mostafa Hamed; Mayla, Ahmed Mahmoud; Abouelhoda, Mohamed; Bahnassy, Abeer A

    2016-01-01

    proposed mathematical model may be a useful method for the early detection of different statuses of liver disease co-occurring with HCV infection. PMID:27122667

  13. Transformation of the genital epithelial tract occurs early in California sea lion development

    PubMed Central

    Barragán-Vargas, Cecilia; Montano-Frías, Jorge; Ávila Rosales, Germán; Godínez-Reyes, Carlos R.; Acevedo-Whitehouse, Karina

    2016-01-01

    An unusually high prevalence of metastatic urogenital carcinoma has been observed in free-ranging California sea lions stranded off the coast of California in the past two decades. No cases have been reported for sea lions in the relatively unpolluted Gulf of California. We investigated occurrence of genital epithelial transformation in 60 sea lions (n=57 pups and 3 adult females) from the Gulf of California and examined whether infection by a viral pathogen previously found to be associated with urogenital carcinoma accounted for such alterations. We also explored the contribution of MHC class II gene expression on transformation. Cellular alterations, such as squamous cell atypia (ASC), atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions were observed in 42% of the pups and in 67% of the adult females. Normal genital epithelium was more common in male than female pups. ASC was five times more likely to occur in older pups. Epithelial alterations were unrelated to infection by the potentially oncogenic otarine type I gammaherpesvirus (OtHV-1), but ASCUS was more common in pups with marked and severe inflammation. Expression of MHC class II DRB loci (Zaca DRB-D) by peripheral antigen-presenting leucocytes showed a slightly ‘protective’ effect for ASC. We propose that transformation of the California sea lion genital epithelium is relatively common in young animals, increases with age and is probably the result of infection by an unidentified pathogen. Expression of a specific MHC class II gene, suggestive of presentation of specific antigenic peptides to immune effectors, appears to lower the risk of transformation. Our study provides the first evidence that epithelial transformation of the California sea lion genital tract is relatively common, even from an early age, and raises questions regarding differences in sea lion cancer-detection and -repair success between geographical regions. PMID:27069641

  14. Transformation of the genital epithelial tract occurs early in California sea lion development.

    PubMed

    Barragán-Vargas, Cecilia; Montano-Frías, Jorge; Ávila Rosales, Germán; Godínez-Reyes, Carlos R; Acevedo-Whitehouse, Karina

    2016-03-01

    An unusually high prevalence of metastatic urogenital carcinoma has been observed in free-ranging California sea lions stranded off the coast of California in the past two decades. No cases have been reported for sea lions in the relatively unpolluted Gulf of California. We investigated occurrence of genital epithelial transformation in 60 sea lions (n=57 pups and 3 adult females) from the Gulf of California and examined whether infection by a viral pathogen previously found to be associated with urogenital carcinoma accounted for such alterations. We also explored the contribution of MHC class II gene expression on transformation. Cellular alterations, such as squamous cell atypia (ASC), atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions were observed in 42% of the pups and in 67% of the adult females. Normal genital epithelium was more common in male than female pups. ASC was five times more likely to occur in older pups. Epithelial alterations were unrelated to infection by the potentially oncogenic otarine type I gammaherpesvirus (OtHV-1), but ASCUS was more common in pups with marked and severe inflammation. Expression of MHC class II DRB loci (Zaca DRB-D) by peripheral antigen-presenting leucocytes showed a slightly 'protective' effect for ASC. We propose that transformation of the California sea lion genital epithelium is relatively common in young animals, increases with age and is probably the result of infection by an unidentified pathogen. Expression of a specific MHC class II gene, suggestive of presentation of specific antigenic peptides to immune effectors, appears to lower the risk of transformation. Our study provides the first evidence that epithelial transformation of the California sea lion genital tract is relatively common, even from an early age, and raises questions regarding differences in sea lion cancer-detection and -repair success between geographical regions. PMID:27069641

  15. Transformation of the genital epithelial tract occurs early in California sea lion development.

    PubMed

    Barragán-Vargas, Cecilia; Montano-Frías, Jorge; Ávila Rosales, Germán; Godínez-Reyes, Carlos R; Acevedo-Whitehouse, Karina

    2016-03-01

    An unusually high prevalence of metastatic urogenital carcinoma has been observed in free-ranging California sea lions stranded off the coast of California in the past two decades. No cases have been reported for sea lions in the relatively unpolluted Gulf of California. We investigated occurrence of genital epithelial transformation in 60 sea lions (n=57 pups and 3 adult females) from the Gulf of California and examined whether infection by a viral pathogen previously found to be associated with urogenital carcinoma accounted for such alterations. We also explored the contribution of MHC class II gene expression on transformation. Cellular alterations, such as squamous cell atypia (ASC), atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions were observed in 42% of the pups and in 67% of the adult females. Normal genital epithelium was more common in male than female pups. ASC was five times more likely to occur in older pups. Epithelial alterations were unrelated to infection by the potentially oncogenic otarine type I gammaherpesvirus (OtHV-1), but ASCUS was more common in pups with marked and severe inflammation. Expression of MHC class II DRB loci (Zaca DRB-D) by peripheral antigen-presenting leucocytes showed a slightly 'protective' effect for ASC. We propose that transformation of the California sea lion genital epithelium is relatively common in young animals, increases with age and is probably the result of infection by an unidentified pathogen. Expression of a specific MHC class II gene, suggestive of presentation of specific antigenic peptides to immune effectors, appears to lower the risk of transformation. Our study provides the first evidence that epithelial transformation of the California sea lion genital tract is relatively common, even from an early age, and raises questions regarding differences in sea lion cancer-detection and -repair success between geographical regions.

  16. Risk for Suicidal Ideation and Suicide Attempts Associated with Co-Occurring Depression and Conduct Problems in Early Adolescence

    ERIC Educational Resources Information Center

    Vander Stoep, Ann; Adrian, Molly; Mc Cauley, Elizabeth; Crowell, Sheila E.; Stone, Andrea; Flynn, Cynthia

    2011-01-01

    This study investigates the early manifestation of co-occurring depression and conduct problems as a predictor of heightened risk for later suicidal ideation and behavior in a community sample of 521 adolescents. Self-reported symptoms of depression and conduct problems were evaluated in early 6th grade. Suicidal thoughts and behaviors were…

  17. Risk for Suicidal Ideation and Suicide Attempts Associated with Co-occurring Depression and Conduct Disorders in Early Adolescence

    PubMed Central

    Stoep, Ann Vander; Adrian, Molly; McCauley, Elizabeth; Crowell, Sheila; Stone, Andrea; Flynn, Cynthia

    2013-01-01

    This study investigates the early manifestation of co-occurring depression and conduct disorders as a predictor of heightened risk for later suicidal ideation and behavior in a community sample of 521 adolescents. Self-reported symptoms of depression and conduct disorder were evaluated in early 6th grade. Suicidal thoughts and behaviors were tracked through multiple assessments carried out over the middle school years. Compared to adolescents with depression symptoms only, conduct disorder symptoms only, or low psychopathology, those with co-occurring depression and conduct disorder symptoms had the highest risk for subsequent suicidal ideation, recurrent suicidal behaviors, and suicide attempts. PMID:21463356

  18. Maternal antimullerian hormone as a predictor of fetal aneuploidy occurring in an early pregnancy loss

    PubMed Central

    Shim, So Hyun; Ha, Hyeong In; Jung, Yong Wook; Shim, Sung Shin; Cho, Yeon Kyung; Kim, Ji Youn; Lee, Kyoung Jin; Cha, Dong Hyun; Kim, Soo Hyun

    2015-01-01

    Objective The purpose of the study was to examine the relationship between the parameter representing ovarian reserve and the fetal aneuploidy in early spontaneous miscarriage. Methods A multicenter retrospective cohort study was performed in patients who were diagnosed with early pregnancy loss (≤13 gestational weeks) and examined for fetal karyotype at the CHA Gangnam Medical Center, CHA Bundang Medical Center, and CHA Gumi Medical Center between January 2011 and December 2012. Karyotyping was performed by the Genetic Laboratory of the Fertility Center of CHA Gangnam Medical Center. Medical records were reviewed for demographics, karyotype analysis and hormonal assay of ovarian reserve including antimullerian hormone (AMH) and follicle stimulating hormone. Statistical analysis was performed using SPSS software. Results A total 462 patients were included in this study. The mean age of the patients was 35.31±4.12 years and the mean AMH level was 3.88±3.50 ng/mL (n=195). Two hundred eleven conceptuses (45.7%) of patients showed the euploid and 251 (54.3%) showed the aneuploid. There are significant differences in maternal age, AMH and gestational age between fetal euploid and aneuploid groups (34.46±4.35 vs. 36.04±3.78 years, P<0.001; 4.60±3.86 vs. 3.43±3.18 ng/mL, P=0.022; 7.67±1.54 vs. 8.27±1.46 weeks, P<0.001, respectively). Multivariate analysis revealed that low AMH level and early gestational age were maternal age-independent markers for fetal aneuploid (P<0.001 and P=0.045, respectively). Conclusion Low maternal AMH level might be a predicting marker for fetal aneuploid in early pregnancy loss. PMID:26623414

  19. Microtubule Alterations Occur Early in Experimental Parkinsonism and The Microtubule Stabilizer Epothilone D Is Neuroprotective

    PubMed Central

    Cartelli, Daniele; Casagrande, Francesca; Busceti, Carla Letizia; Bucci, Domenico; Molinaro, Gemma; Traficante, Anna; Passarella, Daniele; Giavini, Erminio; Pezzoli, Gianni; Battaglia, Giuseppe; Cappelletti, Graziella

    2013-01-01

    The role of microtubule (MT) dysfunction in Parkinson's disease is emerging. It is still unknown whether it is a cause or a consequence of neurodegeneration. Our objective was to assess whether alterations of MT stability precede or follow axonal transport impairment and neurite degeneration in experimental parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57Bl mice. MPTP induced a time- and dose-dependent increase in fibres with altered mitochondria distribution, and early changes in cytoskeletal proteins and MT stability. Indeed, we observed significant increases in neuron-specific βIII tubulin and enrichment of deTyr tubulin in dopaminergic neurons. Finally, we showed that repeated daily administrations of the MT stabilizer Epothilone D rescued MT defects and attenuated nigrostriatal degeneration induced by MPTP. These data suggest that alteration of ΜΤs is an early event specifically associated with dopaminergic neuron degeneration. Pharmacological stabilization of MTs may be a viable strategy for the management of parkinsonism. PMID:23670541

  20. Selection of early-occurring mutations dictates hormone-independent progression in mouse mammary tumor lines.

    PubMed

    Gattelli, Albana; Zimberlin, María N; Meiss, Roberto P; Castilla, Lucio H; Kordon, Edith C

    2006-11-01

    Mice harboring three mouse mammary tumor virus (MMTV) variants develop pregnancy-dependent (PD) tumors that progress to pregnancy-independent (PI) behavior through successive passages. Herein, we identified 10 predominant insertions in PI transplants from 8 independent tumor lines. These mutations were also detected in small cell populations in the early PD passages. In addition, we identified a new viral insertion upstream of the gene Rspo3, which is overexpressed in three of the eight independent tumor lines and codes for a protein very similar to the recently described protein encoded by Int7. This study suggests that during progression towards hormone independence, clonal expansion of cells with specific mutations might be more relevant than the occurrence of new MMTV insertions.

  1. Early and delayed effects of naturally occurring asbestos on serum biomarkers of inflammation and metabolism.

    PubMed

    Kodavanti, Urmila P; Andrews, Debora; Schladweiler, Mette C; Gavett, Stephen H; Dodd, Darol E; Cyphert, Jaime M

    2014-01-01

    Studies recently showed that intratracheal (IT) instillation of Libby amphibole (LA) increases circulating acute-phase proteins (APP; α-2 macroglobulin, A2M; and α-1 acid glycoprotein, AGP) and inflammatory biomarkers (osteopontin and lipocalin) in rats. In this study, objectives were to (1) compare changes in biomarkers of rats after instillation of different naturally occurring asbestos (NOA) minerals including LA, Sumas Mountain chrysotile (SM), El Dorado Hills tremolite (ED), and Ontario ferroactinolite cleavage fragments (ON), and (2) examine biomarkers after subchronic LA or amosite inhalation exposure. Rat-respirable fractions (aerodynamic diameter approximately 2.5 μm) prepared by water elutriation were delivered via a single IT instillation at doses of 0, 0.5, and 1.5 mg/rat in male F344 rats. Nose-only inhalation exposures were performed at 0, 1, 3.3, and 10 mg/m(3) for LA and at 3.3 mg /m(3) for amosite, 6h/d, 5 d/wk for 13 wk. Inflammation, metabolic syndrome, and cancer biomarkers were analyzed in the serum for up to 18 mo. IT instillation of some asbestos materials significantly increased serum AGP and A2M but to a varying degree (SM = LA > ON = ED). Numerical increases in interleukin (IL)-6 and osteopontin occurred in rats instilled with SM. SM and ED also elevated leptin and insulin at 15 mo, suggesting potential metabolic effects. LA inhalation tended to raise A2M at d 1 but not cytokines. Serum mesothelin appeared to elevate after 18 mo of LA inhalation. These results suggest that the lung injury induced by high levels of asbestos materials may be associated with systemic inflammatory changes and predisposition to insulin resistance.

  2. Occurring of In Vitro Functional Vasculogenic Pericytes from Human Circulating Early Endothelial Precursor Cell Culture.

    PubMed

    Cantoni, Silvia; Bianchi, Francesca; Galletti, Margherita; Olivi, Elena; Alviano, Francesco; Galiè, Nazzareno; Ventura, Carlo

    2015-01-01

    Pericytes are periendothelial cells of the microcirculation which contribute to tissue homeostasis and hemostasis by regulating microvascular morphogenesis and stability. Because of their multipotential ex vivo differentiation capabilities, pericytes are becoming very interesting in regenerative medicine field. Several studies address this issue by attempting to isolate pericyte/mesenchymal-like cells from peripheral blood; however the origin of these cells and their culture conditions are still debated. Here we showed that early Endothelial Progenitor Cells (EPCs) expressing CD45+/CD146+/CD31+ can be a source of cells with pericyte/mesenchymal phenotype and function, identified as human Progenitor Perivascular Cells (hPPCs). We provided evidence that hPPCs have an immunophenotype consistent with Mesenchymal Stem Cells (MSCs) from human adipose tissue (hASCs) and fetal membranes of term placenta (FM-hMSCs). In addition, hPPCs can be subcultured and exhibit expression of pluripotent genes (OCT-4, KLF-4, and NANOG) as well as a remarkable vasculogenic potential. Our findings could be helpful to develop innovative cell-based therapies for future clinical applications with distinct therapeutic purposes. PMID:26064139

  3. Occurring of In Vitro Functional Vasculogenic Pericytes from Human Circulating Early Endothelial Precursor Cell Culture

    PubMed Central

    Bianchi, Francesca; Galletti, Margherita; Galiè, Nazzareno; Ventura, Carlo

    2015-01-01

    Pericytes are periendothelial cells of the microcirculation which contribute to tissue homeostasis and hemostasis by regulating microvascular morphogenesis and stability. Because of their multipotential ex vivo differentiation capabilities, pericytes are becoming very interesting in regenerative medicine field. Several studies address this issue by attempting to isolate pericyte/mesenchymal-like cells from peripheral blood; however the origin of these cells and their culture conditions are still debated. Here we showed that early Endothelial Progenitor Cells (EPCs) expressing CD45+/CD146+/CD31+ can be a source of cells with pericyte/mesenchymal phenotype and function, identified as human Progenitor Perivascular Cells (hPPCs). We provided evidence that hPPCs have an immunophenotype consistent with Mesenchymal Stem Cells (MSCs) from human adipose tissue (hASCs) and fetal membranes of term placenta (FM-hMSCs). In addition, hPPCs can be subcultured and exhibit expression of pluripotent genes (OCT-4, KLF-4, and NANOG) as well as a remarkable vasculogenic potential. Our findings could be helpful to develop innovative cell-based therapies for future clinical applications with distinct therapeutic purposes. PMID:26064139

  4. Genotoxic activity in vivo of the naturally occurring glucoside, cycasin, in the Drosophila wing spot test.

    PubMed

    Kawai, K; Furukawa, H; Hirono, I

    1995-03-01

    Cycasin, methylazoxymethanol-beta-glucoside, is a naturally occurring carcinogenic compound. The genotoxicity of cycasin was assayed in the Drosophila wing spot test. Cycasin induced small single and large single spots on feeding at 10 mumol/g medium. The presence of these spots indicates that cycasin is genotoxic in Drosophila melanogaster. Microorganisms which showed beta-glucosidase activity for cleaving cycasin to toxic aglycon were isolated from gut flora of the Drosophila larvae. Consequently, the Drosophila wing spot test would be useful for mutagenicity screening of other naturally occurring glucosides.

  5. Conduct Problems, Depressive Symptomatology and Their Co-Occurring Presentation in Childhood as Predictors of Adjustment in Early Adolescence

    PubMed Central

    Ingoldsby, Erin M.; Kohl, Gwynne O.; McMahon, Robert J.; Lengua, Liliana

    2009-01-01

    The present study investigated patterns in the development of conduct problems (CP), depressive symptoms, and their co-occurrence, and relations to adjustment problems, over the transition from late childhood to early adolescence. Rates of depressive symptoms and CP during this developmental period vary by gender, yet, few studies involving non-clinical samples have examined co-occurring problems and adjustment outcomes across boys and girls. This study investigates the manifestation and change in CP and depressive symptom patterns in a large, multisite, gender- and ethnically-diverse sample of 431 youth from 5th to 7th grade. Indicators of CP, depressive symptoms, their co-occurrence, and adjustment outcomes were created from multiple reporters and measures. Hypotheses regarding gender differences were tested utilizing both categorical (i.e., elevated symptom groups) and continuous analyses (i.e., regressions predicting symptomatology and adjustment outcomes). Results were partially supportive of the dual failure model (Capaldi, 1991, 1992), with youth with co-occurring problems in 5th grade demonstrating significantly lower academic adjustment and social competence two years later. Both depressive symptoms and CP were risk factors for multiple negative adjustment outcomes. Co-occurring symptomatology and CP demonstrated more stability and was associated with more severe adjustment problems than depressive symptoms over time. Categorical analyses suggested that, in terms of adjustment problems, youth with co-occurring symptomatology were generally no worse off than those with CP-alone, and those with depressive symptoms-alone were similar over time to those showing no symptomatology at all. Few gender differences were noted in the relations among CP, depressive symptoms, and adjustment over time. PMID:16967336

  6. Synthesis and anti-cancer activity of naturally occurring 2,5-diketopiperazines.

    PubMed

    Mollica, Adriano; Costante, Roberto; Fiorito, Serena; Genovese, Salvatore; Stefanucci, Azzurra; Mathieu, Veronique; Kiss, Robert; Epifano, Francesco

    2014-10-01

    Three naturally occurring oxyprenylated diketopiperazines were synthesized and preliminarily tested as growth inhibitory agents in vitro against various cancer cell lines. The compounds were tested on six human cancer cell lines with different sensitivity to proapoptotic stimuli using the MTT colorimetric assay. The data revealed that of the chemicals under study only deoxymicelianamide (11) displayed the highest activity, recording mean IC50 growth inhibitory values ranging from 2 to 23 μM. A comparative study with the non-geranylated saturated derivative of (11) revealed the importance of the presence of the geranyloxy side chain and the exocyclic 2,5-DPK double bond moiety for the observed activity.

  7. Recruiting Older Adults into a Physical Activity Promotion Program: "Active Living Every Day" Offered in a Naturally Occurring Retirement Community

    ERIC Educational Resources Information Center

    Hildebrand, Mary; Neufeld, Peggy

    2009-01-01

    Purpose: This article explores recruitment strategies based on the transtheoretical model (TTM) with older adults living in a naturally occurring retirement community (NORC) to encourage enrollment in a physical activity promotion program, "Active Living Every Day" (ALED). Reasons for participation or nonparticipation are identified. Design and…

  8. Liver Fibrosis Occurs Through Dysregulation of MyD88-dependent Innate B cell Activity

    PubMed Central

    Thapa, Manoj; Chinnadurai, Raghavan; Velazquez, Victoria M.; Tedesco, Dana; Elrod, Elizabeth; Han, Jin-Hwan; Sharma, Prachi; Ibegbu, Chris; Gewirtz, Andrew; Anania, Frank; Pulendran, Bali; Suthar, Mehul S.; Grakoui, Arash

    2015-01-01

    Chronic liver disease mediated by activation of hepatic stellate cells (HSCs) leads to liver fibrosis. Here, we postulated that the immune regulatory properties of HSCs might promote the profibrogenic activity of B cells. Fibrosis is completely attenuated in carbon tetrachloride (CCl4)-treated B cell deficient μMT mice showing that B cells are required. The retinoic acid produced by HSCs augmented B cell survival, plasma cell marker CD138 expression, and IgG production. These activities were reversed following the addition of the retinoic acid inhibitor, LE540. Transcriptional profiling of fibrotic liver B cells revealed an increased expression of genes related to NF-κB activation, proinflammatory cytokine production and CD40 signaling suggesting that these B cells are activated and may be acting as inflammatory cells. Biological validation experiments also revealed increased activation (CD44 and CD86 expressions), constitutive IgG production and secretion of the proinflammatory cytokines TNF-α, MCP-1 and MIP1-α. Likewise targeted deletion of B-cell-intrinsic MyD88 signaling, an innate adaptor with involvement in RA signaling, resulted in reduced infiltration of migratory CD11c+ dendritic cells and Ly6C++ monocytes, and hence reduced liver pathology. Conclusion Our findings demonstrate that liver fibrosis occurs through a mechanism of HSC-mediated augmentation of innate B cell activity and highlight B cells as an important ‘first responders’ of the intrahepatic immune environment. PMID:25711908

  9. Anti-inflammatory activities of eleven Centaurea species occurring in the Carpathian Basin.

    PubMed

    Csupor, Dezső; Widowitz, Ute; Blazsó, Gábor; Laczkó-Zöld, Eszter; Tatsimo, Joel S N; Balogh, Agnes; Boros, Klára; Dankó, Balázs; Bauer, Rudolf; Hohmann, Judit

    2013-04-01

    Our study aimed at the identification of anti-inflammatory activities of different fractions of C. sadleriana extract after per os administration in rats, the identification of the active compounds of the plant and the investigation of the in vitro anti-inflammatory activities of Centaurea species native to or cultivated in the Carpathian Basin. The aerial parts of Centaurea sadleriana Janka have been used in Hungarian folk medicine to treat the wounds of sheep. Methanol extract of C. sadleriana was fractioned by solvent-solvent partitioning. The n-hexane fraction was further fractionated and the anti-inflammatory activities of certain subfractions were confirmed in vivo in rats. The n-hexane and chloroform fraction of the methanol extract of C. sadleriana exhibited remarkable COX-1 and COX-2 inhibiting effects in vitro. Chromatographic separation of the fractions led to the identification of the active subfractions and 11 compounds (α-linolenic acid, γ-linolenic acid, stigmasterol, β-sitosterol, campesterol, vanillin, pectolinarigenin, salvigenin, hispidulin, chrysoeriol and apigenin). The in vitro screening for anti-inflammatory activities of further Centaurea species occurring in the Carpathian Basin (C. adjarica, C. bracteata, C. cataonica, C. cynaroides, C. dealbata, C. indurata, C. macrocephala, C. melitensis, C. nigrescens, C. ruthenica) revealed considerable COX-1 and COX-2 inhibitory activities. Because C. sadleriana is an endangered species native only to the Carpathian Basin, the investigation of more prevalent species is reasonable. PMID:22674731

  10. Poly(anhydride-esters) Comprised Exclusively of Naturally Occurring Antimicrobials and EDTA: Antioxidant and Antibacterial Activities

    PubMed Central

    2015-01-01

    Carvacrol, thymol, and eugenol are naturally occurring phenolic compounds known to possess antimicrobial activity against a range of bacteria, as well as antioxidant activity. Biodegradable poly(anhydride-esters) composed of an ethylenediaminetetraacetic acid (EDTA) backbone and antimicrobial pendant groups (i.e., carvacrol, thymol, or eugenol) were synthesized via solution polymerization. The resulting polymers were characterized to confirm their chemical composition and understand their thermal properties and molecular weight. In vitro release studies demonstrated that polymer hydrolytic degradation was complete after 16 days, resulting in the release of free antimicrobials and EDTA. Antioxidant and antibacterial assays determined that polymer release media exhibited bioactivity similar to that of free compound, demonstrating that polymer incorporation and subsequent release had no effect on activity. These polymers completely degrade into components that are biologically relevant and have the capability to promote preservation of consumer products in the food and personal care industries via antimicrobial and antioxidant pathways. PMID:24702678

  11. Complement activation by apoptotic cells occurs predominantly via IgM and is limited to late apoptotic (secondary necrotic) cells.

    PubMed

    Zwart, Bas; Ciurana, Caroline; Rensink, Irma; Manoe, Rishi; Hack, C Erik; Aarden, Lucien A

    2004-03-01

    Apoptotic cells activate complement via various molecular mechanisms. It is not known which of these mechanisms predominate in a physiological environment. Using Jurkat cells as a model, we investigated complement deposition on vital, early and late apoptotic (secondary necrotic) cells in a physiological medium, human plasma, and established the main molecular mechanism involved in this activation. Upon incubation with recalcified plasma, binding of C3 and C4 to early apoptotic cells was similar to background binding on vital cells. In contrast, late apoptotic (secondary necrotic) cells consistently displayed substantial binding of C4 and C3 and low, but detectable, binding of C1q. Binding of C3 and C4 to the apoptotic cells was abolished by EDTA or Mg-EGTA, and also by C1-inhibitor or a monoclonal antibody that inhibits C1q binding, indicating that complement fixation by the apoptotic cells was mainly dependent on the classical pathway. Late apoptotic cells also consistently bound IgM, in which binding significantly correlated with that of C4 and C3. Depletion of plasma for IgM abolished most of the complement fixation by apoptotic cells, which was restored by supplementation with purified IgM. We conclude that complement binding by apoptotic cells in normal human plasma occurs mainly to late apoptotic, secondary necrotic cells, and that the dominant mechanism involves classical pathway activation by IgM.

  12. Biological activity of some naturally occurring resins, gums and pigments against in vitro LDL oxidation.

    PubMed

    Andrikopoulos, Nikolaos K; Kaliora, Andriana C; Assimopoulou, Andreana N; Papapeorgiou, Vassilios P

    2003-05-01

    Naturally occurring gums and resins with beneficial pharmaceutical and nutraceutical properties were tested for their possible protective effect against copper-induced LDL oxidation in vitro. Chiosmastic gum (CMG) (Pistacia lentiscus var. Chia resin) was the most effective in protecting human LDL from oxidation. The minimum and maximum doses for the saturation phenomena of inhibition of LDL oxidation were 2.5 mg and 50 mg CMG (75.3% and 99.9%, respectively). The methanol/water extract of CMG was the most effective compared with other solvent combinations. CMG when fractionated in order to determine a structure-activity relationship showed that the total mastic essential oil, collofonium-like residue and acidic fractions of CMG exhibited a high protective activity ranging from 65.0% to 77.8%. The other natural gums and resins (CMG resin 'liquid collection', P. terebinthus var. Chia resin, dammar resin, acacia gum, tragacanth gum, storax gum) also tested as above, showed 27.0%-78.8% of the maximum LDL protection. The other naturally occurring substances, i.e. triterpenes (amyrin, oleanolic acid, ursolic acid, lupeol, 18-a-glycyrrhetinic acid) and hydroxynaphthoquinones (naphthazarin, shikonin and alkannin) showed 53.5%-78.8% and 27.0%-64.1% LDL protective activity, respectively. The combination effects (68.7%-76.2% LDL protection) of ursolic-, oleanolic- and ursodeoxycholic- acids were almost equal to the effect (75.3%) of the CMG extract in comparable doses. PMID:12748987

  13. Pathological conformations involving the amino terminus of tau occur early in Alzheimer's disease and are differentially detected by monoclonal antibodies.

    PubMed

    Combs, Benjamin; Hamel, Chelsey; Kanaan, Nicholas M

    2016-10-01

    Conformational changes involving the amino terminus of the tau protein are among the earliest alterations associated with tau pathology in Alzheimer's disease and other tauopathies. This region of tau contains a phosphatase-activating domain (PAD) that is aberrantly exposed in pathological forms of the protein, an event that is associated with disruptions in anterograde fast axonal transport. We utilized four antibodies that recognize the amino terminus of tau, TNT1, TNT2 (a novel antibody), Tau12, and Tau13, to further study this important region. Using scanning alanine mutations in recombinant tau proteins, we refined the epitopes of each antibody. We examined the antibodies' relative abilities to specifically label pathological tau in non-denaturing and denaturing assays to gain insight into some of the mechanistic details of PAD exposure. We then determined the pattern of tau pathology labeled by each antibody in human hippocampal sections at various disease stages in order to characterize PAD exposure in the context of disease progression. The characteristics of reactivity for the antibodies fell into two groups. TNT1 and TNT2 recognized epitopes within amino acids 7-12 and specifically identified recombinant tau aggregates and pathological tau from Alzheimer's disease brains in a conformation-dependent manner. These antibodies labeled early pre-tangle pathology from neurons in early Braak stages and colocalized with thiazine red, a marker of fibrillar pathology, in classic neurofibrillary tangles. However, late tangles were negative for TNT1 and TNT2 indicating a loss of the epitope in later stages of tangle evolution. In contrast, Tau12 and Tau13 both identified discontinuous epitopes in the amino terminus and were unable to differentiate between normal and pathological tau in biochemical and tissue immunohistological assays. Despite the close proximity of these epitopes, the antibodies demonstrated remarkably different abilities to identify pathological

  14. Pathological conformations involving the amino terminus of tau occur early in Alzheimer's disease and are differentially detected by monoclonal antibodies.

    PubMed

    Combs, Benjamin; Hamel, Chelsey; Kanaan, Nicholas M

    2016-10-01

    Conformational changes involving the amino terminus of the tau protein are among the earliest alterations associated with tau pathology in Alzheimer's disease and other tauopathies. This region of tau contains a phosphatase-activating domain (PAD) that is aberrantly exposed in pathological forms of the protein, an event that is associated with disruptions in anterograde fast axonal transport. We utilized four antibodies that recognize the amino terminus of tau, TNT1, TNT2 (a novel antibody), Tau12, and Tau13, to further study this important region. Using scanning alanine mutations in recombinant tau proteins, we refined the epitopes of each antibody. We examined the antibodies' relative abilities to specifically label pathological tau in non-denaturing and denaturing assays to gain insight into some of the mechanistic details of PAD exposure. We then determined the pattern of tau pathology labeled by each antibody in human hippocampal sections at various disease stages in order to characterize PAD exposure in the context of disease progression. The characteristics of reactivity for the antibodies fell into two groups. TNT1 and TNT2 recognized epitopes within amino acids 7-12 and specifically identified recombinant tau aggregates and pathological tau from Alzheimer's disease brains in a conformation-dependent manner. These antibodies labeled early pre-tangle pathology from neurons in early Braak stages and colocalized with thiazine red, a marker of fibrillar pathology, in classic neurofibrillary tangles. However, late tangles were negative for TNT1 and TNT2 indicating a loss of the epitope in later stages of tangle evolution. In contrast, Tau12 and Tau13 both identified discontinuous epitopes in the amino terminus and were unable to differentiate between normal and pathological tau in biochemical and tissue immunohistological assays. Despite the close proximity of these epitopes, the antibodies demonstrated remarkably different abilities to identify pathological

  15. Antioxidant activity, ascorbic acid and total phenol of exotic fruits occurring in Brazil.

    PubMed

    de Assis, Sandra Aparecida; Vellosa, José Carlos Rebuglio; Brunetti, Iguatemy Lourenço; Khalil, Najeh Maissar; Leite, Kátia Maria da Silva Cerqueira; Martins, Antonio Baldo Geraldo; Oliveira, Olga Maria Mascarenhas de Faria

    2009-08-01

    The antioxidant activity, ascorbic acid and phenolic content were studied in 10 exotic fruits from Brazil: abiu, acerola, wax jambu, cashew, mamey sapote, carambola or star fruit, Surinam cherry, longan, sapodilla and jaboticaba. The ascorbic acid was determined by 2,6-dichloroindophenol titrimetic methods and total phenols were measured colorimetrically using the Folin-Ciocalteu reagent. The antioxidant activity was investigated with three different methods: hypochlorous acid scavenging activity, 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation decolorization assay, and 2,2-diphenyl-1-picrylhydrazyl radical scavenging method. The highest content of vitamin C (1,525.00 mg/100 g pulp) occurred in acerola. The total phenol content was higher in abiu, acerola, Surinam cherry and sapodilla. In relation to antioxidant activity, acerola has showed the great values in all three different methods tested. It was found that the fruits have a significant antioxidant effect when tested by each method, respectively, and these antioxidant capacities are promising. The sample concentration also influenced its antioxidant power.

  16. Monitoring Natural Occurring Asbestos in ophiolite sequences and derived soils: implication with human activities

    NASA Astrophysics Data System (ADS)

    Punturo, Rosalda; Bloise, Andrea; Cirrincione, Rosolino

    2016-04-01

    The present contribution focuses on soils that developed on serpentinite-metabasite bedrocks, which could potentially be rich in asbestos minerals and, as a consequence, have a negative impact on agricultural activity and on environmental quality. In order to investigate the natural occurrences of asbestos (NOA) on the surface of the soil formed from serpentinites and metabasite, we selected a study area located in Sila Piccola (Calabrian Peloritani Orogen, southern Italy), where previous studies highlighted the presence of asbestiform minerals within the large ophiolitic sequences that crop out (Punturo et al., 2015; Bloise et al., 2015). Agricultural soil samples have been collected mainly close to urban centres and characterized by using different analytical techniques such as X-ray powder diffraction (XRPD), transmission electron microscopy combined with energy dispersive spectrometry (TEM-EDS), thermogravimetry (TG) and differential scanning calorimetry (DSC) Results pointed out as all the collected soil samples contain serpentine minerals (e.g., chrysotile), asbestos amphiboles, clays, chlorite, muscovite, plagioclase and iron oxides in various amounts. Electron microscope images of the soils show that their contain a variety of aggregating agents such as organic matter and clay in which individual fibres of chrysotile and tremolite-actinolite are trapped. The investigation showed that both serpentinite and metabasite rocks act as a perennial source of contamination for the agriculture lands because of the high amount of tremolite-actinolite found in the studied soil samples developed on such lithotypes. Even if asbestiform minerals usually occur in aggregates which cannot be suspended in the air, agricultural activities such as plowing can destroy these soil aggregates with the creation of dust containing inhalable asbestos fibres that evolve into airborne increasing the exposure of population to them. Since the dispersion of fibres could be associated with

  17. Seizure activity occurring in two dogs after S-ketamine-induction.

    PubMed

    Adami, C; Spadavecchia, C; Casoni, D

    2013-10-01

    Two healthy dogs were anaesthetized to undergo elective orthopaedic procedures. After premedication with methadone and acepromazine, general anaesthesia was induced with midazolam and S-ketamine. Immediately after anaesthetic induction, seizures occurred in both dogs. In the first dog the syndrome was characterized by tonic and clonic motor activity, muscular hypertone, hypersalivation, urination, defecation and hyperthermia. In the second dog muscular twitches of the temporal and masseter regions were observed, followed by increased skeletal muscles tone, hypersalivation, spontaneous urination and increase in body temperature. Recoveries from anaesthesia were uneventful and no seizures were observed. Considering the temporal association between anaesthetic induction and occurrence of seizures, and the fact that other causative factors could not be identified, it is hypothesized that S-ketamine played a role in determining the convulsive phenomena observed in these patients. S-ketamine might carry the potential for inducing seizures in otherwise healthy dogs, despite the concomitant use of GABA-ergic drugs.

  18. Leishmanicidal and cytotoxic activities of extracts and naturally-occurring compounds from two Lauraceae species.

    PubMed

    Sánchez-Suárez, Jeysson; Coy-Barrera, Ericsson; Cuca, Luis Enrique; Delgado, Gabriela

    2011-02-01

    The in vitro leishmanicidal effects of ethanolic extracts and fifteen naturally-occurring compounds (five lignans, eight neolignans, a diterpene and a dihydrochalcone), obtained from Pleurothyrium cinereum and Ocotea macrophylla, were evaluated on promastigotes of Leishmania panamensis and L. braziliensis. In addition, in order to determine the selective action on Leishmania species as a safety principle, in vitro cytotoxicity on J774 cells was also evaluated for test compounds and extracts. One extract and seven compounds showed activity against Leishmania parasites at different levels. Dihydroflavokawin B (8) was found to be the most potent antileishmanial compound on both parasites, whilst (+)-otobaphenol (14), was found to be the most selective compound on L. panamensis. PMID:21425681

  19. A Transient Metabolic Recovery from Early Life Glucose Intolerance in Cystic Fibrosis Ferrets Occurs During Pancreatic Remodeling.

    PubMed

    Yi, Yaling; Sun, Xingshen; Gibson-Corley, Katherine; Xie, Weiliang; Liang, Bo; He, Nan; Tyler, Scott R; Uc, Aliye; Philipson, Louis H; Wang, Kai; Hara, Manami; Ode, Katie Larson; Norris, Andrew W; Engelhardt, John F

    2016-05-01

    Cystic fibrosis (CF)-related diabetes in humans is intimately related to exocrine pancreatic insufficiency, yet little is known about how these 2 disease processes simultaneously evolve in CF. In this context, we examined CF ferrets during the evolution of exocrine pancreatic disease. At 1 month of age, CF ferrets experienced a glycemic crisis with spontaneous diabetic-level hyperglycemia. This occurred during a spike in pancreatic inflammation that was preceded by pancreatic fibrosis and loss of β-cell mass. Surprisingly, there was spontaneous normalization of glucose levels at 2-3 months, with intermediate hyperglycemia thereafter. Mixed meal tolerance was impaired at all ages, but glucose intolerance was not detected until 4 months. Insulin secretion in response to hyperglycemic clamp and to arginine was impaired. Insulin sensitivity, measured by euglycemic hyperinsulinemic clamp, was normal. Pancreatic inflammation rapidly diminished after 2 months of age during a period where β-cell mass rose and gene expression of islet hormones, peroxisome proliferator-activated receptor-γ, and adiponectin increased. We conclude that active CF exocrine pancreatic inflammation adversely affects β-cells but is followed by islet resurgence. We predict that very young humans with CF may experience a transient glycemic crisis and postulate that pancreatic inflammatory to adipogenic remodeling may facilitate islet adaptation in CF. PMID:26862997

  20. CXCL10 triggers early microglial activation in the cuprizone model.

    PubMed

    Clarner, Tim; Janssen, Katharina; Nellessen, Lara; Stangel, Martin; Skripuletz, Thomas; Krauspe, Barbara; Hess, Franz-Martin; Denecke, Bernd; Beutner, Clara; Linnartz-Gerlach, Bettina; Neumann, Harald; Vallières, Luc; Amor, Sandra; Ohl, Kim; Tenbrock, Klaus; Beyer, Cordian; Kipp, Markus

    2015-04-01

    A broad spectrum of diseases is characterized by myelin abnormalities and/or oligodendrocyte pathology. In most, if not all, of these diseases, early activation of microglia occurs. Our knowledge regarding the factors triggering early microglia activation is, however, incomplete. In this study, we used the cuprizone model to investigate the temporal and causal relationship of oligodendrocyte apoptosis and early microglia activation. Genome-wide gene expression studies revealed the induction of distinct chemokines, among them Cxcl10, Ccl2, and Ccl3 in cuprizone-mediated oligodendrocyte apoptosis. Early microglia activation was unchanged in CCL2- and CCL3-deficient knockouts, but was significantly reduced in CXCL10-deficient mice, resulting in an amelioration of cuprizone toxicity at later time points. Subsequent in vitro experiments revealed that recombinant CXCL10 induced migration and a proinflammatory phenotype in cultured microglia, without affecting their phagocytic activity or proliferation. In situ hybridization analyses suggest that Cxcl10 mRNA is mainly expressed by astrocytes, but also oligodendrocytes, in short-term cuprizone-exposed mice. Our results show that CXCL10 actively participates in the initiation of microglial activation. These findings have implications for the role of CXCL10 as an important mediator during the initiation of neuroinflammatory processes associated with oligodendrocyte pathology.

  1. Telomerase Activity is Downregulated Early During Human Brain Development

    PubMed Central

    Ishaq, Abbas; Hanson, Peter S.; Morris, Christopher M.; Saretzki, Gabriele

    2016-01-01

    Changes in hTERT splice variant expression have been proposed to facilitate the decrease of telomerase activity during fetal development in various human tissues. Here, we analyzed the expression of telomerase RNA (hTR), wild type and α-spliced hTERT in developing human fetal brain (post conception weeks, pcw, 6–19) and in young and old cortices using qPCR and correlated it to telomerase activity measured by TRAP assay. Decrease of telomerase activity occurred early during brain development and correlated strongest to decreased hTR expression. The expression of α-spliced hTERT increased between pcw 10 and 19, while that of wild type hTERT remained unchanged. Lack of expression differences between young and old cortices suggests that most changes seem to occur early during human brain development. Using in vitro differentiation of neural precursor stem cells (NPSCs) derived at pcw 6 we found a decrease in telomerase activity but no major expression changes in telomerase associated genes. Thus, they do not seem to model the mechanisms for the decrease in telomerase activity in fetal brains. Our results suggest that decreased hTR levels, as well as transient increase in α-spliced hTERT, might both contribute to downregulation of telomerase activity during early human brain development between 6 and 17 pcw. PMID:27322326

  2. Similarity of risk and protective behaviors among African-American pre- and early adolescent members of naturally occurring friendship groups.

    PubMed

    Fang, X; Stanton, B; Li, X; Romer, D; Galbraith, J; Feigelman, S

    1996-01-01

    To determine whether self-reported risk and protective behaviors, expectations, and attitudes are more similar among African-American early adolescents within a community-based friendship group than across groups, a cross-sectional study was conducted among 382 African-American youth 9 through 15 years of age forming 76 community-based groups of 3 through 10 same-gender friends. Each member of the friendship group reported his/her own past involvement in nine risk behaviors (sexual intercourse, substance abuse, drug-trafficking, and other delinquent activities) and two protective behaviors (high academic performance and regular church attendance) and their expectations and feelings regarding several of these behaviors. Intraclass correlation coefficients were calculated overall and by gender and age. Members were generally more similar within friendship groups than across groups with regard to several risk behaviors and expectations including sexual intercourse and drug-trafficking. Particularly striking was the similarity among members of "junior" friendship groups (e.g., median age of youth < 11 years) of both risk and protective behaviors and expectations. The finding of enhanced similarity of risk behaviors and expectations among members within groups suggests that intervention delivery through community-based friendship groups may be a useful approach for risk prevention efforts targeting pre-adolescent African-American youth living in low-income settings. PMID:8982522

  3. Early Childhood: Activity Books and Resource Guides.

    ERIC Educational Resources Information Center

    National Center on Educational Media and Materials for the Handicapped, Columbus, OH.

    Selected from the National Instructional Materials Information System (NIMIS)--a computer based on-line interactive retrieval system on special education materials--the bibliography covers 59 activity books and resource guides for developing skills at the early childhood level. Entries are presented in order of NIMIS accession number and include…

  4. L-tryptophan reacts with naturally occurring and food-occurring phenolic aldehydes to give phenolic tetrahydro-beta-carboline alkaloids: activity as antioxidants and free radical scavengers.

    PubMed

    Herraiz, Tomas; Galisteo, Juan; Chamorro, Cristina

    2003-04-01

    The reaction between the essential amino acid l-tryptophan and flavoring or naturally occurring phenyl and phenolic aldehydes was studied, and the alkaloidal reaction products were characterized by NMR and HPLC-MS. Benzaldehyde, vanillin, syringaldehyde, salicylaldehyde, and anisaldehyde condensed with l-tryptophan in aqueous-acidic media affording the corresponding phenolic tetrahydro-beta-carboline-3-carboxylic acid as two diastereoisomers, 1S,3S-cis and 1R,3S-trans. With the exception of benzaldehyde, the rest of the aldehydes needed heating conditions (70 degrees C) to significantly form tetrahydro-beta-carbolines over time with the cyclization highly favored at low pH. This suggests a likely formation of these compounds under conditions that may occur in foods, food processing, or cooking. The new phenolic tetrahydro-beta-carboline alkaloids were assayed, for the first time, for their activity as free radical scavengers and antioxidants and showed good antioxidant properties with Trolox equivalent antioxidant capacity (TEAC) values much higher than those of ascorbic acid and the water soluble vitamin E analogue, Trolox, in the 2,2'-azinobis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) assay.

  5. ATP-mediated vasodilatation occurs via activation of inwardly rectifying potassium channels in humans.

    PubMed

    Crecelius, Anne R; Kirby, Brett S; Luckasen, Gary J; Larson, Dennis G; Dinenno, Frank A

    2012-11-01

    Circulating ATP possesses unique vasomotor properties in humans and has been hypothesized to play a role in vascular control under a variety of physiological conditions. However, the primary downstream signalling mechanisms underlying ATP-mediated vasodilatation remain unclear. The purpose of the present experiment was to determine whether ATP-mediated vasodilatation is independent of nitric oxide (NO) and prostaglandin (PG) synthesis and occurs primarily via the activation of Na(+)/K(+)-ATPase and inwardly rectifying potassium (K(IR)) channels in humans. In all protocols, young healthy adults were studied and forearm vascular conductance (FVC) was calculated from forearm blood flow (measured via venous occlusion plethysmography) and intra-arterial blood pressure to quantify local vasodilatation. Vasodilator responses (%FVC) during intra-arterial ATP infusions were unchanged following combined inhibition of NO and PGs (n = 8; P > 0.05) whereas the responses to KCl were greater (P < 0.05). Combined infusion of ouabain (to inhibit Na(+)/K(+)-ATPase) and barium chloride (BaCl(2); to inhibit K(IR) channels) abolished KCl-mediated vasodilatation (n = 6; %FVC = 134 ± 13 vs. 4 ± 5%; P < 0.05), demonstrating effective blockade of direct vascular hyperpolarization. The vasodilator responses to three different doses of ATP were inhibited on average 56 ± 5% (n = 16) following combined ouabain plus BaCl(2) infusion. In follow-up studies, BaCl(2) alone inhibited the vasodilator responses to ATP on average 51 ± 3% (n = 6), which was not different than that observed for combined ouabain plus BaCl(2) administration. Our novel results indicate that the primary mechanism of ATP-mediated vasodilatation is vascular hyperpolarization via activation of K(IR) channels. These observations translate in vitro findings to humans in vivo and may help explain the unique vasomotor properties of intravascular ATP in the human circulation.

  6. ATP-mediated vasodilatation occurs via activation of inwardly rectifying potassium channels in humans

    PubMed Central

    Crecelius, Anne R; Kirby, Brett S; Luckasen, Gary J; Larson, Dennis G; Dinenno, Frank A

    2012-01-01

    Circulating ATP possesses unique vasomotor properties in humans and has been hypothesized to play a role in vascular control under a variety of physiological conditions. However, the primary downstream signalling mechanisms underlying ATP-mediated vasodilatation remain unclear. The purpose of the present experiment was to determine whether ATP-mediated vasodilatation is independent of nitric oxide (NO) and prostaglandin (PG) synthesis and occurs primarily via the activation of Na+/K+-ATPase and inwardly rectifying potassium (KIR) channels in humans. In all protocols, young healthy adults were studied and forearm vascular conductance (FVC) was calculated from forearm blood flow (measured via venous occlusion plethysmography) and intra-arterial blood pressure to quantify local vasodilatation. Vasodilator responses (%ΔFVC) during intra-arterial ATP infusions were unchanged following combined inhibition of NO and PGs (n= 8; P > 0.05) whereas the responses to KCl were greater (P < 0.05). Combined infusion of ouabain (to inhibit Na+/K+-ATPase) and barium chloride (BaCl2; to inhibit KIR channels) abolished KCl-mediated vasodilatation (n= 6; %ΔFVC = 134 ± 13 vs. 4 ± 5%; P < 0.05), demonstrating effective blockade of direct vascular hyperpolarization. The vasodilator responses to three different doses of ATP were inhibited on average 56 ± 5% (n= 16) following combined ouabain plus BaCl2 infusion. In follow-up studies, BaCl2 alone inhibited the vasodilator responses to ATP on average 51 ± 3% (n= 6), which was not different than that observed for combined ouabain plus BaCl2 administration. Our novel results indicate that the primary mechanism of ATP-mediated vasodilatation is vascular hyperpolarization via activation of KIR channels. These observations translate in vitro findings to humans in vivo and may help explain the unique vasomotor properties of intravascular ATP in the human circulation. PMID:22777673

  7. The competition plot: a simple test of whether two reactions occur at the same active site.

    PubMed Central

    Chevillard, C; Cárdenas, M L; Cornish-Bowden, A

    1993-01-01

    The competition plot is a method for determining whether or not two enzyme-catalysed reactions occur at the same active site. It is a plot of total rate against p, where p varies from 0 to 1 and specifies the concentrations (1-p)a0 and pb0 of two substrates in terms of reference concentrations a0 and b0 chosen so as to give the same rates at p = 0 and p = 1. If the two substrates react at the same site, the competition plot gives a horizontal straight line, i.e. the total rate is independent of p. Independent reactions at two separate sites give a curve with a maximum; separate reactions with cross-inhibition generate curves with either maxima or minima according to whether the Michaelis constants of the two substrates are smaller or larger than their inhibition constants in the other reactions. Although ambiguous results can sometimes arise, experimental strategies exist for avoiding them, for example working as close as possible to the lower of the two limiting rates. When tested with yeast hexokinase, the plot indicated phosphorylation of glucose and fructose at the same site. Conversely, with a mixture of yeast hexokinase and galactokinase it indicated phosphorylation of glucose and galactose at different sites. In both cases the observed behaviour agreed with the known properties of the enzymes. A slight modification to the definition of this plot allows it to be applied also to enzymes that deviate from Michaelis-Menten kinetics. PMID:8424801

  8. How Did a Major Confined Flare Occur in Super Solar Active Region 12192?

    NASA Astrophysics Data System (ADS)

    Jiang, Chaowei; Wu, S. T.; Yurchyshyn, Vasyl; Wang, Haiming; Feng, Xueshang; Hu, Qiang

    2016-09-01

    We study the physical mechanism of a major X-class solar flare that occurred in the super NOAA active region (AR) 12192 using data-driven numerical magnetohydrodynamic (MHD) modeling complemented with observations. With the evolving magnetic fields observed at the solar surface as bottom boundary input, we drive an MHD system to evolve self-consistently in correspondence with the realistic coronal evolution. During a two-day time interval, the modeled coronal field has been slowly stressed by the photospheric field evolution, which gradually created a large-scale coronal current sheet, i.e., a narrow layer with intense current, in the core of the AR. The current layer was successively enhanced until it became so thin that a tether-cutting reconnection between the sheared magnetic arcades was set in, which led to a flare. The modeled reconnecting field lines and their footpoints match well the observed hot flaring loops and the flare ribbons, respectively, suggesting that the model has successfully “reproduced” the macroscopic magnetic process of the flare. In particular, with simulation, we explained why this event is a confined eruption—the consequence of the reconnection is a shared arcade instead of a newly formed flux rope. We also found a much weaker magnetic implosion effect compared to many other X-class flares.

  9. Lipotoxicity in steatohepatitis occurs despite an increase in tricarboxylic acid cycle activity.

    PubMed

    Patterson, Rainey E; Kalavalapalli, Srilaxmi; Williams, Caroline M; Nautiyal, Manisha; Mathew, Justin T; Martinez, Janie; Reinhard, Mary K; McDougall, Danielle J; Rocca, James R; Yost, Richard A; Cusi, Kenneth; Garrett, Timothy J; Sunny, Nishanth E

    2016-04-01

    The hepatic tricarboxylic acid (TCA) cycle is central to integrating macronutrient metabolism and is closely coupled to cellular respiration, free radical generation, and inflammation. Oxidative flux through the TCA cycle is induced during hepatic insulin resistance, in mice and humans with simple steatosis, reflecting early compensatory remodeling of mitochondrial energetics. We hypothesized that progressive severity of hepatic insulin resistance and the onset of nonalcoholic steatohepatitis (NASH) would impair oxidative flux through the hepatic TCA cycle. Mice (C57/BL6) were fed a high-trans-fat high-fructose diet (TFD) for 8 wk to induce simple steatosis and NASH by 24 wk. In vivo fasting hepatic mitochondrial fluxes were determined by(13)C-nuclear magnetic resonance (NMR)-based isotopomer analysis. Hepatic metabolic intermediates were quantified using mass spectrometry-based targeted metabolomics. Hepatic triglyceride accumulation and insulin resistance preceded alterations in mitochondrial metabolism, since TCA cycle fluxes remained normal during simple steatosis. However, mice with NASH had a twofold induction (P< 0.05) of mitochondrial fluxes (μmol/min) through the TCA cycle (2.6 ± 0.5 vs. 5.4 ± 0.6), anaplerosis (9.1 ± 1.2 vs. 16.9 ± 2.2), and pyruvate cycling (4.9 ± 1.0 vs. 11.1 ± 1.9) compared with their age-matched controls. Induction of the TCA cycle activity during NASH was concurrent with blunted ketogenesis and accumulation of hepatic diacylglycerols (DAGs), ceramides (Cer), and long-chain acylcarnitines, suggesting inefficient oxidation and disposal of excess free fatty acids (FFA). Sustained induction of mitochondrial TCA cycle failed to prevent accretion of "lipotoxic" metabolites in the liver and could hasten inflammation and the metabolic transition to NASH.

  10. Lipotoxicity in steatohepatitis occurs despite an increase in tricarboxylic acid cycle activity.

    PubMed

    Patterson, Rainey E; Kalavalapalli, Srilaxmi; Williams, Caroline M; Nautiyal, Manisha; Mathew, Justin T; Martinez, Janie; Reinhard, Mary K; McDougall, Danielle J; Rocca, James R; Yost, Richard A; Cusi, Kenneth; Garrett, Timothy J; Sunny, Nishanth E

    2016-04-01

    The hepatic tricarboxylic acid (TCA) cycle is central to integrating macronutrient metabolism and is closely coupled to cellular respiration, free radical generation, and inflammation. Oxidative flux through the TCA cycle is induced during hepatic insulin resistance, in mice and humans with simple steatosis, reflecting early compensatory remodeling of mitochondrial energetics. We hypothesized that progressive severity of hepatic insulin resistance and the onset of nonalcoholic steatohepatitis (NASH) would impair oxidative flux through the hepatic TCA cycle. Mice (C57/BL6) were fed a high-trans-fat high-fructose diet (TFD) for 8 wk to induce simple steatosis and NASH by 24 wk. In vivo fasting hepatic mitochondrial fluxes were determined by(13)C-nuclear magnetic resonance (NMR)-based isotopomer analysis. Hepatic metabolic intermediates were quantified using mass spectrometry-based targeted metabolomics. Hepatic triglyceride accumulation and insulin resistance preceded alterations in mitochondrial metabolism, since TCA cycle fluxes remained normal during simple steatosis. However, mice with NASH had a twofold induction (P< 0.05) of mitochondrial fluxes (μmol/min) through the TCA cycle (2.6 ± 0.5 vs. 5.4 ± 0.6), anaplerosis (9.1 ± 1.2 vs. 16.9 ± 2.2), and pyruvate cycling (4.9 ± 1.0 vs. 11.1 ± 1.9) compared with their age-matched controls. Induction of the TCA cycle activity during NASH was concurrent with blunted ketogenesis and accumulation of hepatic diacylglycerols (DAGs), ceramides (Cer), and long-chain acylcarnitines, suggesting inefficient oxidation and disposal of excess free fatty acids (FFA). Sustained induction of mitochondrial TCA cycle failed to prevent accretion of "lipotoxic" metabolites in the liver and could hasten inflammation and the metabolic transition to NASH. PMID:26814015

  11. Early axonal loss accompanied by impaired endocytosis, abnormal axonal transport, and decreased microtubule stability occur in the model of Krabbe's disease.

    PubMed

    Teixeira, Carla Andreia; Miranda, Catarina Oliveira; Sousa, Vera Filipe; Santos, Telma Emanuela; Malheiro, Ana Rita; Solomon, Melani; Maegawa, Gustavo H; Brites, Pedro; Sousa, Mónica Mendes

    2014-06-01

    In Krabbe's disease (KD), a leukodystrophy caused by β-galactosylceramidase deficiency, demyelination and a myelin-independent axonopathy contributes to the severe neuropathology. Beyond axonopathy, we show that in Twitcher mice, a model of KD, a decreased number of axons both in the PNS and in the CNS, and of neurons in dorsal root ganglia (DRG), occurred before the onset of demyelination. Despite the early axonal loss, and although in vitro Twitcher neurites degenerated over time, Twitcher DRG neurons displayed an initial neurite overgrowth and, following sciatic nerve injury, Twitcher axons were regeneration-competent, at a time point where axonopathy was already ongoing. Psychosine, the toxic substrate that accumulates in KD, induced lipid raft clustering. At the mechanistic level, TrkA recruitment to lipid rafts was dysregulated in Twitcher neurons, and defective activation of the ERK1/2 and AKT pathways was identified. Besides defective recruitment of signaling molecules to lipid rafts, the early steps of endocytosis and the transport of endocytic and synaptic vesicles were impaired in Twitcher DRG neurons. Defects in axonal transport, specifically in the retrograde component, correlated with decreased levels of dynein, abnormal levels of post-translational tubulin modifications and decreased microtubule stability. The identification of the axonal defects that precede demyelination in KD, together with the finding that Twitcher axons are regeneration-competent when axonopathy is already installed, opens new windows of action to effectively correct the neuropathology that characterizes this disorder.

  12. On the Total Energy Deposition Between Periodically Occurring Activations of the Aurora

    NASA Technical Reports Server (NTRS)

    Spann, James F., Jr.; Germany, G. A.; Parks, G. K.; Brittnacher, M. J.; Winglee, R. W.

    1998-01-01

    Total energy deposition in the northern latitudes is used in models to determine the state of the magnetosphere. It is known that on occasion, a series of intensifications of the aurora occur that are regularly spaced. The energy profile of the total energy deposited reflects this occurance. What can be said of the state of the magnetosphere based on these profiles. We present the result of a study which looks at several of these periods when a series of intensifications occur. Conclusions as to what the magnetosphere may be doing are presented.

  13. A Form of Perforant Path LTP Can Occur without ERK1/2 Phosphorylation or Immediate Early Gene Induction

    ERIC Educational Resources Information Center

    Steward, Oswald; Huang, Fen; Guzowski, John F.

    2007-01-01

    Stimulation paradigms that induce perforant path long-term potentiation (LTP) initiate phosphorylation of ERK1/2 and induce expression of a variety of immediate early genes (IEGs). These events are thought to be critical components of the mechanism for establishing the changes in synaptic efficacy that endure for hours or longer. Here we show that…

  14. First Generation Gene Expression Signature for Early Prediction of Late Occurring Hematological Acute Radiation Syndrome in Baboons.

    PubMed

    Port, M; Herodin, F; Valente, M; Drouet, M; Lamkowski, A; Majewski, M; Abend, M

    2016-07-01

    We implemented a two-stage study to predict late occurring hematologic acute radiation syndrome (HARS) in a baboon model based on gene expression changes measured in peripheral blood within the first two days after irradiation. Eighteen baboons were irradiated to simulate different patterns of partial-body and total-body exposure, which corresponded to an equivalent dose of 2.5 or 5 Gy. According to changes in blood cell counts the surviving baboons (n = 17) exhibited mild (H1-2, n = 4) or more severe (H2-3, n = 13) HARS. Blood samples taken before irradiation served as unexposed control (H0, n = 17). For stage I of this study, a whole genome screen (mRNA microarrays) was performed using a portion of the samples (H0, n = 5; H1-2, n = 4; H2-3, n = 5). For stage II, using the remaining samples and the more sensitive methodology, qRT-PCR, validation was performed on candidate genes that were differentially up- or down-regulated during the first two days after irradiation. Differential gene expression was defined as significant (P < 0.05) and greater than or equal to a twofold difference above a H0 classification. From approximately 20,000 genes, on average 46% appeared to be expressed. On day 1 postirradiation for H2-3, approximately 2-3 times more genes appeared up-regulated (1,418 vs. 550) or down-regulated (1,603 vs. 735) compared to H1-2. This pattern became more pronounced at day 2 while the number of differentially expressed genes decreased. The specific genes showed an enrichment of biological processes coding for immune system processes, natural killer cell activation and immune response (P = 1 × E-06 up to 9 × E-14). Based on the P values, magnitude and sustained differential gene expression over time, we selected 89 candidate genes for validation using qRT-PCR. Ultimately, 22 genes were confirmed for identification of H1-3 classifications and seven genes for identification of H2-3 classifications using qRT-PCR. For H1-3 classifications, most genes were

  15. Naturally occurring plant isoquinoline N-oxide alkaloids: their pharmacological and SAR activities.

    PubMed

    Dembitsky, Valery M; Gloriozova, Tatyana A; Poroikov, Vladimir V

    2015-01-15

    The present review describes research on novel natural isoquinoline alkaloids and their N-oxides isolated from different plant species. More than 200 biological active compounds have shown confirmed antimicrobial, antibacterial, antitumor, and other activities. The structures, origins, and reported biological activities of a selection of isoquinoline N-oxides alkaloids are reviewed. With the computer program PASS some additional SAR (structure-activity relationship) activities are also predicted, which point toward new possible applications of these compounds. This review emphasizes the role of isoquinoline N-oxides alkaloids as an important source of leads for drug discovery.

  16. Aphidicolin-resistant polyomavirus and subgenomic cellular DNA synthesis occur early in the differentiation of cultured myoblasts to myotubes.

    PubMed Central

    DePolo, N J; Villarreal, L P

    1993-01-01

    Small DNA viruses have been historically used as probes of cellular control mechanisms of DNA replication, gene expression, and differentiation. Polyomavirus (Py) DNA replication is known to be linked to differentiation of may cells, including myoblasts. In this report, we use this linkage in myoblasts to simultaneously examine (i) cellular differentiation control of Py DNA replication and (ii) an unusual type of cellular and Py DNA synthesis during differentiation. Early proposals that DNA synthesis was involved in the induced differentiation of myoblasts to myotubes were apparently disproved by reliance on inhibitors of DNA synthesis (cytosine arabinoside and aphidicolin), which indicated that mitosis and DNA replication are not necessary for differentiation. Theoretical problems with the accessibility of inactive chromatin to trans-acting factors led us to reexamine possible involvement of DNA replication in myoblast differentiation. We show here that Py undergoes novel aphidicolin-resistant net DNA synthesis under specific conditions early in induced differentiation of myoblasts (following delayed aphidicolin addition). Under similar conditions, we also examined uninfected myoblast DNA synthesis, and we show that soon after differentiation induction, a period of aphidicolin-resistant cellular DNA synthesis can also be observed. This drug-resistant DNA synthesis appears to be subgenomic, not contributing to mitosis, and more representative of polyadenylated than of nonpolyadenylated RNA. These results renew the possibility that DNA synthesis plays a role in myoblast differentiation and suggest that the linkage of Py DNA synthesis to differentiation may involve a qualitative cellular alteration in Py DNA replication. Images PMID:8389922

  17. Antioxidant and cytotoxic activities of naturally occurring phenolic and related compounds: a comparative study.

    PubMed

    Rao, Yerra Koteswara; Geethangili, Madamanchi; Fang, Shih-Hua; Tzeng, Yew-Min

    2007-09-01

    The antioxidant (DPPH radical and superoxide anion scavenging activities), and cytotoxic (in tumor, Jurkat, PC-3, Colon 205, HepG2, and normal PBMCs cells) activities of 16 plant phenolic or related compounds were evaluated in vitro. Different categories compounds corresponding to 10 flavonoids, three lignans, two phenolic acids, and a catechin showed significant mean differences in antioxidant and cytotoxic activities. Particularly, the flavonols, quercetin (3) and tiliroside (11) possess significant antioxidant activity, as well as cytotoxic activity against Jurkat; and Jurkat and HepG2 cells, respectively. In contrast, the flavanone, 5,7-dimethoxy-3',4'-methylenedioxyflavanone (7), and homoisoflavonoid, isobonducellin (10) shown to have no significant antioxidant activity, but exhibited potent cytotoxic activity in Jurkat and HepG2 cells, while moderate growth inhibition against Colon205 cells. Interestingly, none of these derivatives shown to have toxicity toward normal peripheral blood mononuclear cells, over the concentration range tested (5-200 microM). Cytotoxic activities of some natural flavonoids identified in the medicinal plants were evaluated for the first time.

  18. Activation of ATM depends on chromatin interactions occurring before induction of DNA damage.

    PubMed

    Kim, Yong-Chul; Gerlitz, Gabi; Furusawa, Takashi; Catez, Frédéric; Nussenzweig, Andre; Oh, Kyu-Seon; Kraemer, Kenneth H; Shiloh, Yosef; Bustin, Michael

    2009-01-01

    Efficient and correct responses to double-stranded breaks (DSB) in chromosomal DNA are crucial for maintaining genomic stability and preventing chromosomal alterations that lead to cancer. The generation of DSB is associated with structural changes in chromatin and the activation of the protein kinase ataxia-telangiectasia mutated (ATM), a key regulator of the signalling network of the cellular response to DSB. The interrelationship between DSB-induced changes in chromatin architecture and the activation of ATM is unclear. Here we show that the nucleosome-binding protein HMGN1 modulates the interaction of ATM with chromatin both before and after DSB formation, thereby optimizing its activation. Loss of HMGN1 or ablation of its ability to bind to chromatin reduces the levels of ionizing radiation (IR)-induced ATM autophosphorylation and the activation of several ATM targets. IR treatments lead to a global increase in the acetylation of Lys 14 of histone H3 (H3K14) in an HMGN1-dependent manner and treatment of cells with histone deacetylase inhibitors bypasses the HMGN1 requirement for efficient ATM activation. Thus, by regulating the levels of histone modifications, HMGN1 affects ATM activation. Our studies identify a new mediator of ATM activation and demonstrate a direct link between the steady-state intranuclear organization of ATM and the kinetics of its activation after DNA damage. PMID:19079244

  19. Characterization of pectinase activity for enology from yeasts occurring in Argentine Bonarda grape.

    PubMed

    Merín, María Gabriela; Martín, María Carolina; Rantsiou, Kalliopi; Cocolin, Luca; de Ambrosini, Vilma Inés Morata

    2015-01-01

    Pectinolytic enzymes are greatly important in winemaking due to their ability to degrade pectic polymers from grape, contributing to enhance process efficiency and wine quality. This study aimed to analyze the occurrence of pectinolytic yeasts during spontaneous fermentation of Argentine Bonarda grape, to select yeasts that produce extracellular pectinases and to characterize their pectinolytic activity under wine-like conditions. Isolated yeasts were grouped using PCR-DGGE and identified by partial sequencing of 26S rRNA gene. Isolates comprised 7 genera, with Aureobasidium pullulans as the most predominant pectinolytic species, followed by Rhodotorula dairenensis and Cryptococcus saitoi. No pectinolytic activity was detected among ascomycetous yeasts isolated on grapes and during fermentation, suggesting a low occurrence of pectinolytic yeast species in wine fermentation ecosystem. This is the first study reporting R. dairenensis and Cr. saitoi species with pectinolytic activity. R. dairenensis GM-15 produced pectinases that proved to be highly active at grape pH, at 12 °C, and under ethanol and SO2 concentrations usually found in vinifications (pectinase activity around 1.1 U/mL). This strain also produced cellulase activity at 12 °C and pH 3.5, but did not produce β-glucosidase activity under these conditions. The strain showed encouraging enological properties for its potential use in low-temperature winemaking. PMID:26413065

  20. Characterization of pectinase activity for enology from yeasts occurring in Argentine Bonarda grape

    PubMed Central

    Merín, María Gabriela; Martín, María Carolina; Rantsiou, Kalliopi; Cocolin, Luca; de Ambrosini, Vilma Inés Morata

    2015-01-01

    Pectinolytic enzymes are greatly important in winemaking due to their ability to degrade pectic polymers from grape, contributing to enhance process efficiency and wine quality. This study aimed to analyze the occurrence of pectinolytic yeasts during spontaneous fermentation of Argentine Bonarda grape, to select yeasts that produce extracellular pectinases and to characterize their pectinolytic activity under wine-like conditions. Isolated yeasts were grouped using PCR-DGGE and identified by partial sequencing of 26S rRNA gene. Isolates comprised 7 genera, with Aureobasidium pullulans as the most predominant pectinolytic species, followed by Rhodotorula dairenensis and Cryptococcus saitoi. No pectinolytic activity was detected among ascomycetous yeasts isolated on grapes and during fermentation, suggesting a low occurrence of pectinolytic yeast species in wine fermentation ecosystem. This is the first study reporting R. dairenensis and Cr. saitoi species with pectinolytic activity. R. dairenensis GM-15 produced pectinases that proved to be highly active at grape pH, at 12 °C, and under ethanol and SO2 concentrations usually found in vinifications (pectinase activity around 1.1 U/mL). This strain also produced cellulase activity at 12 °C and pH 3.5, but did not produce β-glucosidase activity under these conditions. The strain showed encouraging enological properties for its potential use in low-temperature winemaking. PMID:26413065

  1. Transient reductions in leukocyte/endothelium interaction occur early in hyperoxic lung injury, as seen using scanning electron microscopy (SEM)

    SciTech Connect

    Allen, C.B.; Tucker, A. Colorado State Univ., Ft. Collins )

    1990-02-26

    Exposure of rats to 100% O{sub 2} results in an increased number of neutrophils seen adjacent to pulmonary capillary endothelium. Preliminary studies suggested that serotonin depletion using parachlorophenyalanine (PCPA) accelerated the progression of hyperoxic lung injury. The authors chose to study leukocyte margination in hyperoxic lung injury using SEM to survey pulmonary vessels >20 um diameter in serotonin-intact rats and serotonin-depleted rats exposed to 100% O{sub 2} for 12, 24, 36, 48, 56, and 60 hours. In control rats, the average density of marginated leukocytes was 1,703/mm{sup 2}. At 12, 24 and 36 hours of exposure to 100% O{sub 2}, this density had been reduced to 599/mm{sup 2}, 683/mm{sup 2} and 733/mm{sup 2}, respectively (p{le}0.05). At 48 hours, the leukocyte density, 2,009/mm{sup 2}, was greater than the control value. At 60 hours of exposure, leukocyte densities were not different from control values. Serotonin-depletion did not significantly change this pattern. These findings suggest that hyperoxia causes an earlier change in endothelium/leukocyte interaction than previously thought, and that after early reductions in leukocyte margination, leukocyte densities rebound toward control levels by 48 hours of exposure.

  2. Encrustation and Atherosclerosis: The Analogy Between Early in Vivo Lesions and Deposits Which Occur in Extracorporeal Circulations

    PubMed Central

    Murphy, E. A.; Rowsell, H. C.; Downie, H. G.; Robinson, G. A.; Mustard, J. F.

    1962-01-01

    A study was made of the relation between the pattern and topography of thrombus formation in models of various vessel configurations coupled into extracorporeal shunts in swine and the development of atherosclerosis at corresponding sites on swine aortas. The pattern and distribution of deposits formed in the models were strikingly similar to the pattern and distribution of incipient atherosclerosis at comparable sites in the vascular tree. The earliest and only consistent component of the flow chamber deposits was the blood platelet. The platelet deposits would frequently stain with oil red O. The cholesterol level of washed human platelets was found to show a good correlation with that in the plasma. This evidence suggests that deposition of particulate matter (chiefly platelets), largely determined by the hydraulic factors, may be an important factor in the early, as well as later, stages of atherosclerosis. ImagesFigs. 10a and bFig. 13Fig. 21Fig. 1Fig. 3Figs. 4a and bFig. 5Fig. 6aFig. 6bFig. 7Fig. 8Fig. 9Fig. 11Fig. 12Fig. 14Fig. 15Fig. 16Fig. 17Fig. 18Fig. 19Fig. 20 PMID:14477412

  3. Increased hurricane activity during the Early Toarcian extreme warmth

    NASA Astrophysics Data System (ADS)

    Bodin, Stephane; Krencker, Francois-Nicolas; Suan, Guillaume; Heimhofer, Ulrich; Immenhauser, Adrian

    2014-05-01

    Theoretical considerations led to the postulation that hurricane activity should increase on a warming planet. Finding physical proof for this relationship remains, however, a difficult task since no clear trend is yet emerging from records of present-day anthropogenic warming. The geological past offers the opportunity to test this hypothesis by assessing episodes of extreme warming events, such as the Toarcian Oceanic Anoxic Event (T-OAE, Early Jurassic, ca. 180 Ma). The T-OAE is characterized by a rapid 4-5°C global warming likely induced by the massive release of greenhouse gases into the atmosphere as a consequence of the activity of the Karoo-Ferrar large igneous province. Within the western Tethyan realm (Morocco, Portugal, France, England, etc.), a systematic increase in the occurrence of storm-related deposits is observed within the shallow-water sediments deposited during the T-OAE, notably at its onset. Increased tempestite occurrences can be observed in both siliciclastic- and carbonate-dominated environments. In the Moroccan High Atlas, hummocky cross-stratification (HCS) occurs ubiquitous within the T-OAE, but is otherwise rare in this tide-dominated basin. Interestingly, the palaeolatitude of the High Atlas Basin (10°N during the Early Jurassic) rules out winter storms as the driving mechanism behind the formation of the HCS, and suggests therefore a significant increase of tropical hurricane activity associated with the Early Toarcian global warming.

  4. Evidence that endoplasmic reticulum (ER) stress and caspase-4 activation occur in human neutrophils.

    PubMed

    Binet, François; Chiasson, Sonia; Girard, Denis

    2010-01-01

    Apoptosis can result from activation of three major pathways: the extrinsic, the intrinsic, and the most recently identified endoplasmic reticulum (ER) stress-mediated pathway. While the two former pathways are known to be operational in human polymorphonuclear neutrophils (PMNs), the existence of the ER stress-mediated pathway, generally involving caspase-4, has never been reported in these cells. Recently, we have documented that arsenic trioxide (ATO) induced apoptosis in human PMNs by a mechanism that needs to be further investigated. In this study, using immunofluorescence and electron microscopy, we present evidence of ER alterations in PMNs activated by the ER stress inducer arsenic trioxide (ATO). Several key players of the unfolded protein response, including GRP78, GADD153, ATF6, XBP1 and eIF2alpha are expressed and activated in PMNs treated with ATO or other ER stress inducers. Although caspase-4 is expressed and activated in neutrophils, treatment with a caspase-4 inhibitor did not attenuate the pro-apoptotic effect of ATO at a concentration that reverses caspase-4 processing and activation. Our results demonstrate for the first time that the ER stress-mediated apoptotic pathway operates in human neutrophils.

  5. Wasp recruitment to the T cell:APC contact site occurs independently of Cdc42 activation.

    PubMed

    Cannon, J L; Labno, C M; Bosco, G; Seth, A; McGavin, M H; Siminovitch, K A; Rosen, M K; Burkhardt, J K

    2001-08-01

    Cdc42 and WASP are critical regulators of actin polymerization whose function during T cell signaling is poorly understood. Using a novel reagent that specifically detects Cdc42-GTP in fixed cells, we found that activated Cdc42 localizes to the T cell:APC contact site in an antigen-dependent manner. TCR signaling alone was sufficient to induce localization of Cdc42-GTP, and functional Lck and Zap-70 kinases were required. WASP also localized to the T cell:APC contact site in an antigen-dependent manner. Surprisingly, WASP localization was independent of the Cdc42 binding domain but required the proline-rich domain. Our results indicate that localized WASP activation requires the integration of multiple signals: WASP is recruited via interaction with SH3 domain-containing proteins and is activated by Cdc42-GTP concentrated at the same site. PMID:11520460

  6. Limitations to lake trout (Salvelinus namaycush) rehabilitation in the Great Lakes imposed by biotic interactions occurring at early life stages

    USGS Publications Warehouse

    Jones, Michael L.; Eck, Gary W.; Evans, David O.; Fabrizio, Mary C.; Hoff, Michael H.; Hudson, Patrick L.; Janssen, John; Jude, David; O'Gorman, Robert; Savino, Jacqueline F.

    1995-01-01

    We examine evidence that biotic factors, particularly predation, may be limiting early survival of wild lake trout (Salvelinus namaycush) juveniles in many areas of the Great Lakes. The Great Lakes contain numerous potential predators of lake trout eggs and fry, some of which are recent invaders, and most of which were probably absent when lake trout most recently re-invaded the Great Lakes after the last ice age. Simple quantitative models of predation suggest that plausible assumptions about prey densities, predator feeding rates, and duration of exposure of predator to prey can lead to very high estimates of predation mortality, in some instances approaching 100%. Indirect evidence from inter-Great Lake comparisons and inland lake examples also suggest that biotic factors may impede successful lake trout colonization. Our synthesis of the evidence leads to recommendations for research to better define field feeding rates of lake trout egg and fry predators and comparative studies of densities of potential egg and fry predators on lake trout spawning reefs. Management options should be designed to provide useful information as well as achieve short-term goals. From a management standpoint we recommend that: newly constructed lake trout reefs should be placed well away from concentrations of potential predators; offshore spawning reefs should be stocked; salmonine stocking, nutrient abatement, and commercial harvest of alewives should all be considered as options to enhance survival of young lake trout; hatchery lake trout should not be stocked at sites where wild lake trout are showing signs of recovery; and exotic species expansions or introductions must be curtailed to maintain or improve on our recent successes in lake trout rehabilitation.

  7. Activation of Endothelial Nitric Oxide (eNOS) Occurs through Different Membrane Domains in Endothelial Cells.

    PubMed

    Tran, Jason; Magenau, Astrid; Rodriguez, Macarena; Rentero, Carles; Royo, Teresa; Enrich, Carlos; Thomas, Shane R; Grewal, Thomas; Gaus, Katharina

    2016-01-01

    Endothelial cells respond to a large range of stimuli including circulating lipoproteins, growth factors and changes in haemodynamic mechanical forces to regulate the activity of endothelial nitric oxide synthase (eNOS) and maintain blood pressure. While many signalling pathways have been mapped, the identities of membrane domains through which these signals are transmitted are less well characterized. Here, we manipulated bovine aortic endothelial cells (BAEC) with cholesterol and the oxysterol 7-ketocholesterol (7KC). Using a range of microscopy techniques including confocal, 2-photon, super-resolution and electron microscopy, we found that sterol enrichment had differential effects on eNOS and caveolin-1 (Cav1) colocalisation, membrane order of the plasma membrane, caveolae numbers and Cav1 clustering. We found a correlation between cholesterol-induced condensation of the plasma membrane and enhanced high density lipoprotein (HDL)-induced eNOS activity and phosphorylation suggesting that cholesterol domains, but not individual caveolae, mediate HDL stimulation of eNOS. Vascular endothelial growth factor (VEGF)-induced and shear stress-induced eNOS activity was relatively independent of membrane order and may be predominantly controlled by the number of caveolae on the cell surface. Taken together, our data suggest that signals that activate and phosphorylate eNOS are transmitted through distinct membrane domains in endothelial cells.

  8. Dynamo model for grand maxima of solar activity: can superflares occur on the Sun?

    NASA Astrophysics Data System (ADS)

    Kitchatinov, L. L.; Olemskoy, S. V.

    2016-07-01

    Recent data on superflares on Sun-like stars and radiocarbon data on solar activity in the past are both indicative of transient epochs of unusually high magnetic activity. We propose an explanation for the grand activity maxima in the framework of a solar dynamo model with fluctuating parameters. Solar-type dynamos are oscillatory because of the combination of the solar-type differential rotation with positive (in the Northern hemisphere) alpha-effect. An artificial reversal of the sign in the alpha-effect changes the dynamo to a steady regime with hundreds of times larger magnetic energy compared to the amplitude of the cyclic dynamo. Sufficiently large and durable fluctuations reversing the sign of the alpha-effect during the growth phase of a magnetic cycle can, therefore, cause a transient change to a steady dynamo with considerably increased magnetic energy. This qualitative scenario for grand activity maxima is supported by computations of the dynamo model with a fluctuating alpha-effect. The computed statistics of several thousand magnetic cycles gives examples of cycles with very high magnetic energy. Our preliminary estimations, however, suggest that the probability of solar superflares is extremely low.

  9. Chlorine-Susceptible and Chlorine-Resistant Type 021N Bacteria Occurring in Bulking Activated Sludges

    PubMed Central

    Séka, M. A.; Kalogo, Y.; Hammes, F.; Kielemoes, J.; Verstraete, W.

    2001-01-01

    Two filamentous bacteria causing bulking in two activated sludges were examined. Investigations using morphological features, staining techniques, and fluorescent in situ hybridization identified both filaments as type 021N. However, an examination of the effect of chlorine on the sludges revealed a chlorine-susceptible type 021N in one sludge and a chlorine-resistant type 021N in the other. PMID:11679359

  10. Activation of Endothelial Nitric Oxide (eNOS) Occurs through Different Membrane Domains in Endothelial Cells.

    PubMed

    Tran, Jason; Magenau, Astrid; Rodriguez, Macarena; Rentero, Carles; Royo, Teresa; Enrich, Carlos; Thomas, Shane R; Grewal, Thomas; Gaus, Katharina

    2016-01-01

    Endothelial cells respond to a large range of stimuli including circulating lipoproteins, growth factors and changes in haemodynamic mechanical forces to regulate the activity of endothelial nitric oxide synthase (eNOS) and maintain blood pressure. While many signalling pathways have been mapped, the identities of membrane domains through which these signals are transmitted are less well characterized. Here, we manipulated bovine aortic endothelial cells (BAEC) with cholesterol and the oxysterol 7-ketocholesterol (7KC). Using a range of microscopy techniques including confocal, 2-photon, super-resolution and electron microscopy, we found that sterol enrichment had differential effects on eNOS and caveolin-1 (Cav1) colocalisation, membrane order of the plasma membrane, caveolae numbers and Cav1 clustering. We found a correlation between cholesterol-induced condensation of the plasma membrane and enhanced high density lipoprotein (HDL)-induced eNOS activity and phosphorylation suggesting that cholesterol domains, but not individual caveolae, mediate HDL stimulation of eNOS. Vascular endothelial growth factor (VEGF)-induced and shear stress-induced eNOS activity was relatively independent of membrane order and may be predominantly controlled by the number of caveolae on the cell surface. Taken together, our data suggest that signals that activate and phosphorylate eNOS are transmitted through distinct membrane domains in endothelial cells. PMID:26977592

  11. Extraction and evaluation of natural occurring bioactive compounds and change in antioxidant activity during red winemaking.

    PubMed

    Ivanova-Petropulos, Violeta; Durakova, Sanja; Ricci, Arianna; Parpinello, Giuseppina P; Versari, Andrea

    2016-06-01

    Phenolic composition of red wines from Stanušina, a grape variety indigenous of the Republic of Macedonia, was compared with the regional Vranec and the international Cabernet Sauvignon. The extent of skin contact (i.e. maceration time) on levels of phenolic compounds and antioxidant activity of wines was evaluated. A total of 19 phenolic compounds were identified and quantified. Among these malvidin-3-glucoside and its derivatives were the major compounds, while caftaric acid was the predominant cinnamic acid derivative, followed by catechin, the main flavan-3-ol. The concentration of hydroxycinnamic acids, anthocyanins and (+)-catechin ranged from 224 to 511 mg/L, 22 to 360 mg/L and 26 20 to 375 mg/L, respectively and peaked at 3rd, 6th and 9th day of maceration, respectively. However, prolong maceration slightly decreased their concentration. Stanušina wines presented high levels of hydroxycinnamic acids and antioxidant activity. PMID:27478219

  12. DSL ligand endocytosis physically dissociates Notch1 heterodimers before activating proteolysis can occur.

    PubMed

    Nichols, James T; Miyamoto, Alison; Olsen, Samantha L; D'Souza, Brendan; Yao, Christine; Weinmaster, Gerry

    2007-02-12

    Cleavage of Notch by furin is required to generate a mature, cell surface heterodimeric receptor that can be proteolytically activated to release its intracellular domain, which functions in signal transduction. Current models propose that ligand binding to heterodimeric Notch (hNotch) induces a disintegrin and metalloprotease (ADAM) proteolytic release of the Notch extracellular domain (NECD), which is subsequently shed and/or endocytosed by DSL ligand cells. We provide evidence for NECD release and internalization by DSL ligand cells, which, surprisingly, did not require ADAM activity. However, losses in either hNotch formation or ligand endocytosis significantly decreased NECD transfer to DSL ligand cells, as well as signaling in Notch cells. Because endocytosis-defective ligands bind hNotch, but do not dissociate it, additional forces beyond those produced through ligand binding must function to disrupt the intramolecular interactions that keep hNotch intact and inactive. Based on our findings, we propose that mechanical forces generated during DSL ligand endocytosis function to physically dissociate hNotch, and that dissociation is a necessary step in Notch activation.

  13. Daily activity patterns of two co-occurring tropical satyrine butterflies.

    PubMed

    Enrique Cardoso Peixoto, Paulo; Benson, Woodruff W

    2009-01-01

    Adult males and females of many insect species are expected to adjust their daily activity pattern in order to avoid stressful climatic conditions and increase the chances to encounter sexual partners. Using scan sampling methods associated with focal individual observations it was found that two satyrine butterflies of similar size and morphology, Hermeuptychia hermes (Fabricius) (Leptidoptera: Nymphalidae) and Paryphthimoides phronius (Godart), show completely different daily activity patterns on forest edges in southeastern Brazil. Hermeuptychia hermes presents one abundance peak in the morning and another in the late afternoon, while P. phronius abundance peaks in the mid-day, remaining stable until 1700 h. This difference is probably due to the occurrence of territorial behavior in the later species. The beginning of territorial defense by P. phronius males coincided with the time of new-born female activity. However, newly hatched females were not sexually receptive. The afternoon territoriality in male P. phronius may be in part related to mate acquisition. However, why the abundance of H. hermes decreases when the abundance of P. phronius increases is less clear.

  14. Using naturally occurring polysaccharides to align molecules with nonlinear optical activity

    NASA Technical Reports Server (NTRS)

    Prasthofer, Thomas

    1996-01-01

    The Biophysics and Advanced Materials Branch of the Microgravity Science and Applications Division at Marshall Space Flight Center has been investigating polymers with the potential for nonlinear optical (NLO) applications for a number of years. Some of the potential applications for NLO materials include optical communications, computing, and switching. To this point the branch's research has involved polydiacetylenes, phthalocyanins, and other synthetic polymers which have inherent NLO properties. The aim of the present research is to investigate the possibility of using naturally occurring polymers such as polysaccharides or proteins to trap and align small organic molecules with useful NLO properties. Ordering molecules with NLO properties enhances 3rd order nonlinear effects and is required for 2nd order nonlinear effects. Potential advantages of such a system are the flexibility to use different small molecules with varying chemical and optical properties, the stability and cost of the polymers, and the ability to form thin, optically transparent films. Since the quality of any polymer films depends on optimizing ordering and minimizing defects, this work is particularly well suited for microgravity experiments. Polysaccharide and protein polymers form microscopic crystallites which must align to form ordered arrays. The ordered association of crystallites is disrupted by gravity effects and NASA research on protein crystal growth has demonstrated that low gravity conditions can improve crystal quality.

  15. Cellulase occurs in multiple active forms in ripe avocado fruit mesocarp.

    PubMed

    Kanellis, A K; Kalaitzis, P

    1992-02-01

    The existence of multiple forms of avocado (Persea americana Mill. cv Hass) cellulase in crude protein extracts of ripe avocado fruit is reported. Cellulase was separated into at least 11 multiple forms by native isoelectric focusing in the pH range between 4 and 7 and visualized by both activity staining using Congo red and immunostaining. The enzyme components were acidic proteins with isoelectric points in the range of pH 5.10 to 6.80, the predominant forms having isoelectric points of 5.60, 5.80, 5.95, and 6.20. All 11 forms were immunologically related with molecular masses of 54 kilodaltons.

  16. Amino acid substitutions in naturally occurring variants of ail result in altered invasion activity.

    PubMed Central

    Beer, K B; Miller, V L

    1992-01-01

    Yersinia enterocolitica is the causative agent of a variety of gastrointestinal syndromes ranging from acute enteritis to mesenteric lymphadenitis. In addition, systemic infections resulting in high mortality rates can occur in elderly and immunocompromised patients. More than 50 serotypes of Y. enterocolitica have been identified, but only a few of them commonly cause disease in otherwise healthy hosts. Those serotypes that cause disease have been divided into two groups, American and non-American, based on their geographical distributions, biotypes, and pathogenicity. We have been studying two genes, inv and ail, from Y. enterocolitica that confer in tissue culture assays an invasive phenotype that strongly correlates with virulence. Some differences between the American and non-American serotypes at the ail locus were noted previously and have been investigated further in this report. The ail locus was cloned from seven Y. enterocolitica strains (seven different serotypes). Although the different clones produced similar amounts of Ail, the product of the ail gene from non-American serotypes (AilNA) was less able to promote invasion by Escherichia coli than was the product of the ail gene from American serotypes (AilA). This difference is probably due to one or more of the eight amino acid changes found in the derived amino acid sequence for the mature form of AilNA compared with that of AilA. Seven of these changes are predicted to be in cell surface domains of the protein (a model for the proposed folding of Ail within the outer membrane is presented). These results are discussed in relation to the growing family of outer membrane proteins, which includes Lom from bacteriophage lambda, PagC from salmonella typhimurium, and OmpX from Enterobacter cloacae. Images PMID:1370953

  17. NEW STRATEGIES FOR THE ISOLATION AND ACTIVITY DETERMINATION OF NATURALLY OCCURRING TYPE-4 GLUTATHIONE PEROXIDASE

    PubMed Central

    Kernstock, Robert M.; Girotti, Albert W.

    2008-01-01

    Type 4 glutathione peroxidase (GPx4) is a widely expressed mammalian selenoenzyme known to play a vital role in cytoprotection against lipid hydroperoxide (LOOH)-mediated oxidative stress and regulation of oxidative signaling cascades. Since prokaryotes are not equipped to express mammalian selenoproteins, preparation of recombinant GPx4 via commonly used bacterial transformation is not feasible. A published procedure for isolating the enzyme from rat testis employs affinity chromatography on bromosulfophthalein-glutathione-linked agarose as the penultimate step in purification. Since this resin is no longer commercially available and preparing it in satisfactory operational form is tedious, we have developed an alternative purification approach based on sequential anion exchange, size exclusion, and cation exchange chromatography. Final preparations were found to be essentially homogeneous in GPx4 (Mr ∼20 kDa), as demonstrated by SDS-PAGE with protein staining and immunoblotting. Specific enzymatic activity was determined using a novel thin layer chromatographic approach in which the kinetics of phosphatidylcholine hydroperoxide loss or cholesterol-7α-hydroperoxide loss were monitored. A >400-fold purification of active enzyme has been attained. The relatively straightforward isolation procedure described should prove valuable for further functional studies on GPx4, e.g. how its ability to catalyze LOOH reduction compares with that of other LOOH detoxifying enzymes. PMID:18723092

  18. Cis-Golgi cisternal assembly and biosynthetic activation occur sequentially in plants and algae

    PubMed Central

    Donohoe, Bryon S.; Kang, Byung-Ho; Gerl, Mathias J.; Gergely, Zachary R.; McMichael, Colleen M.; Bednarek, Sebastian Y.; Staehelin, L. Andrew

    2013-01-01

    The cisternal progression/maturation model of Golgi trafficking predicts that cis-Golgi cisternae are formed de novo on the cis-side of the Golgi. Here we describe structural and functional intermediates of the cis cisterna assembly process in high-pressure frozen algae (Scherffelia dubia, Chlamydomonas reinhardtii) and plants (Arabidopsis thaliana, Dionaea muscipula; Venus Flytrap) as determined by electron microscopy, electron tomography and immuno-electron microscopy techniques. Our findings are as follows: (1) The cis-most (C1) Golgi cisternae are generated de novo from cisterna initiators produced by the fusion of 3–5 COPII vesicles in contact with a C2 cis cisterna. (2) COPII vesicles fuel the growth of the initiators, which then merge into a coherent C1 cisterna. (3) When a C1 cisterna nucleates its first cisterna initiator it becomes a C2 cisterna. (4) C2-Cn cis cisternae grow through COPII vesicle fusion. (5) ER-resident proteins are recycled from cis cisternae to the ER via COPIa-type vesicles. (6) In S. dubia the C2 cisternae are capable of mediating the self-assembly of scale protein complexes. (7) In plants, ~90% of native α-mannosidase I localizes to medial Golgi cisternae. (8) Biochemical activation of cis cisternae appears to coincide with their conversion to medial cisternae via recycling of medial cisterna enzymes. We propose how the different cis cisterna assembly intermediates of plants and algae may actually be related to those present in the ERGIC and in the pre-cis Golgi cisterna layer in mammalian cells. PMID:23369235

  19. Cis-Golgi cisternal assembly and biosynthetic activation occur sequentially in plants and algae.

    PubMed

    Donohoe, Bryon S; Kang, Byung-Ho; Gerl, Mathias J; Gergely, Zachary R; McMichael, Colleen M; Bednarek, Sebastian Y; Staehelin, L Andrew

    2013-05-01

    The cisternal progression/maturation model of Golgi trafficking predicts that cis-Golgi cisternae are formed de novo on the cis-side of the Golgi. Here we describe structural and functional intermediates of the cis cisterna assembly process in high-pressure frozen algae (Scherffelia dubia, Chlamydomonas reinhardtii) and plants (Arabidopsis thaliana, Dionaea muscipula; Venus flytrap) as determined by electron microscopy, electron tomography and immuno-electron microscopy techniques. Our findings are as follows: (i) The cis-most (C1) Golgi cisternae are generated de novo from cisterna initiators produced by the fusion of 3-5 COPII vesicles in contact with a C2 cis cisterna. (ii) COPII vesicles fuel the growth of the initiators, which then merge into a coherent C1 cisterna. (iii) When a C1 cisterna nucleates its first cisterna initiator it becomes a C2 cisterna. (iv) C2-Cn cis cisternae grow through COPII vesicle fusion. (v) ER-resident proteins are recycled from cis cisternae to the ER via COPIa-type vesicles. (vi) In S. dubia the C2 cisternae are capable of mediating the self-assembly of scale protein complexes. (vii) In plants, ∼90% of native α-mannosidase I localizes to medial Golgi cisternae. (viii) Biochemical activation of cis cisternae appears to coincide with their conversion to medial cisternae via recycling of medial cisterna enzymes. We propose how the different cis cisterna assembly intermediates of plants and algae may actually be related to those present in the ERGIC and in the pre-cis Golgi cisterna layer in mammalian cells.

  20. Early modern human settlement of Europe north of the Alps occurred 43,500 years ago in a cold steppe-type environment

    PubMed Central

    Nigst, Philip R.; Haesaerts, Paul; Damblon, Freddy; Frank-Fellner, Christa; Mallol, Carolina; Viola, Bence; Götzinger, Michael; Niven, Laura; Trnka, Gerhard; Hublin, Jean-Jacques

    2014-01-01

    The first settlement of Europe by modern humans is thought to have occurred between 50,000 and 40,000 calendar years ago (cal B.P.). In Europe, modern human remains of this time period are scarce and often are not associated with archaeology or originate from old excavations with no contextual information. Hence, the behavior of the first modern humans in Europe is still unknown. Aurignacian assemblages—demonstrably made by modern humans—are commonly used as proxies for the presence of fully behaviorally and anatomically modern humans. The site of Willendorf II (Austria) is well known for its Early Upper Paleolithic horizons, which are among the oldest in Europe. However, their age and attribution to the Aurignacian remain an issue of debate. Here, we show that archaeological horizon 3 (AH 3) consists of faunal remains and Early Aurignacian lithic artifacts. By using stratigraphic, paleoenvironmental, and chronological data, AH 3 is ascribed to the onset of Greenland Interstadial 11, around 43,500 cal B.P., and thus is older than any other Aurignacian assemblage. Furthermore, the AH 3 assemblage overlaps with the latest directly radiocarbon-dated Neanderthal remains, suggesting that Neanderthal and modern human presence overlapped in Europe for some millennia, possibly at rather close geographical range. Most importantly, for the first time to our knowledge, we have a high-resolution environmental context for an Early Aurignacian site in Central Europe, demonstrating an early appearance of behaviorally modern humans in a medium-cold steppe-type environment with some boreal trees along valleys around 43,500 cal B.P. PMID:25246543

  1. Early Adolescence: Active Science for Middle Schoolers.

    ERIC Educational Resources Information Center

    Padilla, Michael; Griffin, Nancy

    1980-01-01

    Describes activities appropriate for involving middle school students as active participants in the learning process. Topics discussed include archaeology, bulletin boards, dramatizations, physics experiments using the human body, oceanography, and ecology. (CS)

  2. Early maladaptive schema-related impairment and co-occurring current major depressive episode-related enhancement of mental state decoding ability in borderline personality disorder.

    PubMed

    Unoka, Zsolt Szabolcs; Fogd, Dóra; Seres, Imola; Kéri, Szabolcs; Csukly, Gábor

    2015-04-01

    Disturbed interpersonal relationships specific to borderline personality disorder (BPD) suggest biased processing of social information. The goal of this study was to examine alterations in mental state decoding (MSD) and their associations with early maladaptive schemas (EMS) that may lead to the misinterpretation of incoming information. In addition, the authors' aim was to evaluate the effects of a co-occurring current major depressive episode (MDE) on the MSD performance of BPD patients. Seventy-eight BPD patients (34 with MDE) and 76 matched healthy controls (HC) were assessed for Reading the Mind in the Eyes Test (RMET) and the level of EMS. The authors found that impairment in the total RMET performance, as well as specific impairment regarding the recognition of positive and neutral items, was associated with EMS, and enhanced vigilance to negative mental states was characteristic to BPD with MDE. Results suggest that MSD ability is altered in two independent ways in BPD. PMID:24932871

  3. Early maladaptive schema-related impairment and co-occurring current major depressive episode-related enhancement of mental state decoding ability in borderline personality disorder.

    PubMed

    Unoka, Zsolt Szabolcs; Fogd, Dóra; Seres, Imola; Kéri, Szabolcs; Csukly, Gábor

    2015-04-01

    Disturbed interpersonal relationships specific to borderline personality disorder (BPD) suggest biased processing of social information. The goal of this study was to examine alterations in mental state decoding (MSD) and their associations with early maladaptive schemas (EMS) that may lead to the misinterpretation of incoming information. In addition, the authors' aim was to evaluate the effects of a co-occurring current major depressive episode (MDE) on the MSD performance of BPD patients. Seventy-eight BPD patients (34 with MDE) and 76 matched healthy controls (HC) were assessed for Reading the Mind in the Eyes Test (RMET) and the level of EMS. The authors found that impairment in the total RMET performance, as well as specific impairment regarding the recognition of positive and neutral items, was associated with EMS, and enhanced vigilance to negative mental states was characteristic to BPD with MDE. Results suggest that MSD ability is altered in two independent ways in BPD.

  4. [A Case of Laparoscopic Surgery for Early Gastric Cancer that Occurred after Coronary Artery Bypass Grafting using the Right Gastroepiploic Artery].

    PubMed

    Kusumoto, Eiji; Ota, Mitsuhiko; Tsutsumi, Norifumi; Hashimoto, Kenkichi; Egashira, Akinori; Sakaguchi, Yoshihisa; Kusumoto, Tetsuya; Ikejiri, Koji

    2015-10-01

    We herein report a case involving a 70-year-old man who was diagnosed with early gastric cancer that occurred after coronary artery bypass grafting (CABG) using the right gastroepiploic artery (RGEA) for effort-induced angina. He was successfully treated by laparoscopic surgery. Preoperative cardiac three-dimensional computed tomography and coronary angiography showed an occlusion of the RGEA graft, which could lead to ligation of the RGEA to dissect the lymph nodes along the RGEA. The laparoscopic approach helps to identify and avoid injury to the RGEA graft because of its enlarged and precise viewing field compared with laparotomy followed by retractor placement. Laparoscopic surgery is a useful method in such cases to reduce perioperative complications risk.

  5. N-terminal cleavage of proTGFα occurs at the cell surface by a TACE-independent activity

    PubMed Central

    2005-01-01

    ProTGFα (transforming growth factor α precursor) maturation and conversion into soluble TGFα is a complex process that involves three proteolytic steps. One, that occurs co-translationally, eliminates the signal sequence. Another, occurring at the juxtamembrane domain, solubilizes TGFα. A third cleavage removes the N-terminal extension of proTGFα. This latter step has been poorly studied, mainly because of the rapid kinetics of this cleavage. In the present study, we have designed a strategy to analyse several aspects regarding this N-terminal cleavage. In vivo treatment with the hydroxamate-based metalloprotease inhibitors BB3103 or TAPI-2 (tumour necrosis factor-α protease inhibitor 2) reversibly induced accumulation of forms of proTGFα that included the N-terminal extension. N-terminal shedding was rapid, and occurred at the cell surface. However, the machinery responsible for the N-terminal cleavage was inactive in other cellular sites, such as the endoplasmic reticulum. Experiments of proTGFα expression and maturation in cells deficient in TACE (tumour-necrosis-factor-α-converting enzyme) activity indicated that this protease was dispensable for N-terminal processing of proTGFα in vivo, but was required for regulated cleavage at the C-terminus. These findings indicate that TACE is not involved in N-terminal processing of proTGFα, and suggest differences in the machineries that control the cleavage at both ends of TGFα within its precursor. PMID:15777285

  6. Conservation Seeds Activities Book. An Early Childhood Conservation Education Program.

    ERIC Educational Resources Information Center

    Griffin, Sherri

    This activities book is used with an early childhood conservation education program. The activities are presented in four color-coded sections, each section representing one of the four seasons. Each activity includes a statement of purpose, list of materials needed, instructional strategies, and a list of supplementary activities. In addition to…

  7. Predicting Early Sexual Activity with Behavior Problems Exhibited at School Entry and in Early Adolescence

    ERIC Educational Resources Information Center

    Schofield, Hannah-Lise T.; Bierman, Karen L.; Heinrichs, Brenda; Nix, Robert L.

    2008-01-01

    Youth who initiate sexual intercourse in early adolescence (age 11-14) experience multiple risks, including concurrent adjustment problems and unsafe sexual practices. The current study tested two models describing the links between childhood precursors, early adolescent risk factors, and adolescent sexual activity: a cumulative model and a…

  8. Phosphatase production and activity in Citrobacter freundii and a naturally occurring, heavy-metal-accumulating Citrobacter sp.

    PubMed

    Montgomery, D M; Dean, A C; Wiffen, P; Macaskie, L E

    1995-10-01

    The ability of a naturally occurring Citrobacter sp. to accumulate cadmium has been attributed to cellular precipitation of CdHPO4, utilizing HPO4(2-) liberated via the activity of an overproduced, Cd-resistant acid-type phosphatase. Phosphatase production and heavy metal accumulation by batch cultures of this strain (N14) and a phosphatase-deficient mutant were compared with two reference strains of Citrobacter freundii. Only strain N14 expressed a high level of acid phosphatase and accumulated lanthanum and uranyl ion enzymically. Acid phosphatase is regulated via carbon-starvation; although the C. freundii strains overexpressed phosphatase activity in carbon-limiting continuous culture, this was approximately 20-fold less than the activity of strain N14 grown similarly. Citrobacter strain N14 was originally isolated from a metal-contaminated soil environment; phosphatase overproduction and metal accumulation were postulated as a detoxification mechanism. However, application of Cd-stress, and enrichment for Cd-resistant C. freundii ('training'), reduced the phosphatase activity of this organism by about 50% as compared to Cd-unstressed cultures. The acid phosphatase of C. freundii and Citrobacter N14 had a similar pattern of resistance to some diagnostic reagents. The enzyme of the latter is similar to the PhoN acid phosphatase of Salmonella typhimurium described by other workers; the results are discussed with respect to the known phosphatases of the enterobacteria.

  9. Promoting Physical Activity during Early Childhood

    ERIC Educational Resources Information Center

    Vidoni, Carla; Ignico, Arlene

    2011-01-01

    The prevalence of obesity in children and adolescents from low-income families in the USA has become a significant concern over the last 20 years. One of the major contributors to this problem is the lack of physical activity. The purpose of this paper is to describe initiatives designed to: (1) engage young children in physical activity during…

  10. Early Childhood: Developing Sense-activities.

    ERIC Educational Resources Information Center

    Shirah, Sue; Dorman, Mildred M.

    1989-01-01

    Described are science activities in which students concentrate on their senses and make discoveries with their eyes, ears, noses, mouths, and hands. Suggested experiments include activities involving cooking, tasting, observing, floating and sinking objects, making rain, and stringed musical instruments. (RT)

  11. Increased alveolar plasminogen activator in early asbestosis

    SciTech Connect

    Cantin, A.; Allard, C.; Begin, R.

    1989-03-01

    Alveolar macrophage-derived plasminogen activator (PA) activity is decreased in some chronic interstitial lung diseases such as idiopathic pulmonary fibrosis and sarcoidosis but increased in experimental models of acute alveolitis. Although asbestos fibers can stimulate alveolar macrophages (AM) to release PA in vitro, the effect of chronic asbestos exposure of the lower respiratory tract on lung PA activity remains unknown. The present study was designed to evaluate PA activity of alveolar macrophages and bronchoalveolar lavage (BAL) fluid in asbestos-exposed sheep and asbestos workers. Forty-three sheep were exposed to either 100 mg UICC chrysotile B asbestos in 100 ml phosphate-buffered saline (PBS) or to 100 ml PBS by tracheal infusion every 2 wk for 18 months. At Month 18, chest roentgenograms were analyzed and alveolar macrophage and extracellular fluid PA activity were measured in samples obtained by BAL. Alveolar macrophage PA activity was increased in the asbestos-exposed sheep compared to control sheep (87.2 +/- 17.3 versus 41.1 +/- 7.2 U/10(5) AM-24 h, p less than 0.05) as was the BAL fluid PA activity (674.9 +/- 168.4 versus 81.3 +/- 19.7 U/mg alb-24 h, p less than 0.01). Among the asbestos-exposed sheep, 10 had normal chest roentgenograms (Group SA) and 15 had irregular interstitial opacities (Group SB). Strikingly, whereas Group SA did not differ from the control group in BAL cellularity or PA activity, Group SB had marked increases in alveolar macrophages (p less than 0.005), AM PA activity (p less than 0.02), and BAL PA activity (p less than 0.001) compared to the control group.

  12. Cardiovascular events occur independently of high on-aspirin platelet reactivity and residual COX-1 activity in stable cardiovascular patients.

    PubMed

    Nagatsuka, Kazuyuki; Miyata, Shigeki; Kada, Akiko; Kawamura, Atsushi; Nakagawara, Jyoji; Furui, Eisuke; Takiuchi, Shin; Taomoto, Katsushi; Kario, Kazuomi; Uchiyama, Shinichiro; Saito, Kozue; Nagao, Takehiko; Kitagawa, Kazuo; Hosomi, Naohisa; Tanaka, Keiji; Kaikita, Koichi; Katayama, Yasuo; Abumiya, Takeo; Nakane, Hiroshi; Wada, Hideo; Hattori, Akira; Kimura, Kazumi; Isshiki, Takaaki; Nishikawa, Masakatsu; Yamawaki, Takemori; Yonemoto, Naohiro; Okada, Hiromi; Ogawa, Hisao; Minematsu, Kazuo; Miyata, Toshiyuki

    2016-08-01

    Several studies have indicated that approximately 25 % of patients treated with aspirin exhibit high on-treatment platelet reactivity (HTPR), which is potentially associated with cardiovascular events (CVEs). However, this association is still controversial, since the mechanisms by which HTPR contributes to CVEs remain unclear and a no standardised definition of HTPR has been established. To determine whether HTPR is associated with CVE recurrence and what type of assay would best predict CVE recurrence, we conducted a multicentre prospective cohort study of 592 stable cardiovascular outpatients treated with aspirin monotherapy for secondary prevention. Their HTPR was determined by arachidonic acid- or collagen-induced aggregation assays using two different agonist concentrations. Residual cyclooxygenase (COX)-1 activity was assessed by measuring serum thromboxane (TX)B2 or urinary 11-dehydro TXB2. Shear-induced platelet thrombus formation was also examined. We followed all patients for two years to evaluate how these seven indexes were related to the recurrence of CVEs (cerebral infarction, transient ischaemic attack, myocardial infarction, unstable angina, revascularisation, other arterial thrombosis, or cardiovascular death). Of 583 patients eligible for the analysis, CVEs occurred in 69 (11.8 %). A Cox regression model identified several classical risk factors associated with CVEs. However, neither HTPR nor high residual COX-1 activity was significantly associated with CVEs, even by applying cut-off values suggested in previous reports or a receiver-operating characteristic analysis. In conclusion, recurrence of CVEs occurred independently of HTPR and residual COX-1 activity. Thus, our findings do not support the use of platelet or COX-1 functional testing for predicting clinical outcomes in stable cardiovascular patients. PMID:27098431

  13. Predicting Early Sexual Activity with Behavior Problems Exhibited at School Entry and in Early Adolescence

    PubMed Central

    Schofield, Hannah-Lise T.; Heinrichs, Brenda; Nix, Robert L.

    2009-01-01

    Youth who initiate sexual intercourse in early adolescence (age 11–14) experience multiple risks, including concurrent adjustment problems and unsafe sexual practices, The current study tested two models describing the links between childhood precursors, early adolescent risk factors, and adolescent sexual activity: a cumulative model and a meditational model, A longitudinal sample of 694 boys and girls from four geographical locations was utilized, with data collected from kindergarten through high school. Structural equation models revealed that, irrespective of gender or race, high rates of aggressive disruptive behaviors and attention problems at school entry increased risk for a constellation of problem behaviors in middle school (school maladjustment, antisocial activity, and substance use) which, in turn, promoted the early initiation of sexual activity. Implications are discussed for developmental models of early sexual activity and for prevention programming. PMID:18607716

  14. Setting the Stage for Lifetime Physical Activity in Early Childhood

    ERIC Educational Resources Information Center

    Schneider, Holly; Lounsbery, Monica

    2008-01-01

    The purpose of this article is to provide a rationale and suggestions for emphasizing health-related physical education in preschool settings. In order to accomplish this, it will examine what is currently known about early childhood physical activity, as well as the existing professional preparation and accreditation standards for early childhood…

  15. Experiential Aging Activities and the Early Adolescent.

    ERIC Educational Resources Information Center

    Glover, Elbert D.; And Others

    1981-01-01

    Negative views about the elderly held by adolescents can result in a negative outlook on aging. Physical, mental, and social aging experiential activities are given which can be done at home or at school. (JN)

  16. 50+ Activities for Early Childhood Essential Elements. Volume I.

    ERIC Educational Resources Information Center

    Education Service Center Region 6, Huntsville, TX.

    Written as a companion resource to "Early Childhood Essential Elements," a document developed by the Education Service Center, Region VI, Huntsville, Texas, this first volume of a two-volume activity guide provides activities enhancing children's cognitive, communication, and motor skills. Activities included in the guide are compiled from a…

  17. Early Risk, Attention, and Brain Activation in Adolescents Born Preterm

    ERIC Educational Resources Information Center

    Carmody, Dennis P.; Bendersky, Margaret; Dunn, Stanley M.; DeMarco, J. Kevin; Hegyi, Thomas; Hiatt, Mark; Lewis, Michael

    2006-01-01

    The relations among early cumulative medical risk, cumulative environmental risk, attentional control, and brain activation were assessed in 15-16-year-old adolescents who were born preterm. Functional magnetic resonance imaging found frontal, temporal, and parietal cortex activation during an attention task with greater activation of the left…

  18. Effects of Online Self-Regulation Activities on Physical Activity Among Pregnant and Early Postpartum Women.

    PubMed

    Kim, Hye Kyung; Niederdeppe, Jeff; Graham, Meredith; Olson, Christine; Gay, Geri

    2015-01-01

    Physical and psychological changes that occur during pregnancy present a unique challenge for women's physical activity. Using a theory-based prospective design, this study examines the effects of pregnant women's (a) physical activity cognitions (self-efficacy, outcome expectancy, and safety beliefs) and (b) online self-regulation activities (goal-setting and self-monitoring) on subsequent changes in their physical activity intentions and behavior during pregnancy and immediately postpartum. The authors used data from three panel surveys administered to pregnant women enrolled in a web-based intervention to promote healthy pregnancy and postpartum weight, as well as log data on their use of self-regulatory features on the intervention website. Perceived self-efficacy and perceived safety of physical activity in pregnancy enhanced subsequent intentions to be physically active. Repeated goal-setting and monitoring of those goals helped to maintain positive intentions during pregnancy, but only repeated self-monitoring transferred positive intentions into actual behavior. Theoretically, this study offers a better understanding of the roles of self-regulation activities in the processes of goal-striving. The authors also discuss practical implications for encouraging physical activity among pregnant and early postpartum women.

  19. The Autophagic Process Occurs in Human Bone Metastasis and Implicates Molecular Mechanisms Differently Affected by Rab5a in the Early and Late Stages

    PubMed Central

    Maroni, Paola; Bendinelli, Paola; Resnati, Massimo; Matteucci, Emanuela; Milan, Enrico; Desiderio, Maria Alfonsina

    2016-01-01

    Autophagy favours metastatic growth through fuelling energy and nutrients and resistance to anoikis, typical of disseminated-tumour cells. The autophagic process, mediated by a unique organelle, the autophagosome, which fuses with lysosomes, is divided into three steps. Several stages, especially early omegasome formation and isolation-membrane initiation, remain controversial; molecular mechanisms involve the small-GTPase Rab5a, which regulates vesicle traffic for autophagosome formation. We examined Rab5a involvement in the function of key members of ubiquitin-conjugation systems, Atg7 and LC3-lipidated, interacting with the scaffold-protein p62. Immunohistochemistry of Rab5a was performed in human specimens of bone metastasis and pair-matched breast carcinoma; the autophagic-molecular mechanisms affected by Rab5a were evaluated in human 1833 bone metastatic cells, derived from breast-carcinoma MDA-MB231 cells. To clarify the role of Rab5a, 1833 cells were transfected transiently with Rab5a-dominant negative, and/or stably with the short-hairpin RNA Atg7, were exposed to two inhibitors of autolysosome function, and LC3II and p62 expression was measured. We showed basal autophagy in bone-metastatic cells and the pivotal role of Rab5a together with Beclin 1 between the early stages, elongation of isolation membrane/closed autophagosome mediated by Atg7, and the late-degradative stages. This regulatory network might occur in bone-metastasis and in high-grade dysplastic lesions, preceding invasive-breast carcinoma and conferring phenotypic characteristics for dissemination. PMID:27023526

  20. American History Activators (Early American History).

    ERIC Educational Resources Information Center

    Lacey, Bill

    This document consists of a package of seven separately published "activities" or simulations that allow students to learn about and participate in many of the aspects of United States history that have influenced our present institutions and way of life. The seven units include: (1) First Americans Arrive: 11.000 BC; (2) Puritan General Court,…

  1. A Recently Established Murine Model of Nasal Polyps Demonstrates Activation of B Cells, as Occurs in Human Nasal Polyps.

    PubMed

    Kim, Dong-Young; Lee, Sun Hye; Carter, Roderick G; Kato, Atsushi; Schleimer, Robert P; Cho, Seong H

    2016-08-01

    Animal model systems are invaluable for examining human diseases. Our laboratory recently established a mouse model of nasal polyps (NPs) and investigated similarities and differences between this mouse model and human NPs. We especially focus on the hypothesis that B cell activation occurs during NP generation in the murine model. After induction of ovalbumin-induced allergic rhinosinusitis, 6% ovalbumin and Staphylococcus aureus enterotoxin B (10 ng) were instilled into the nasal cavity of mice three times per week for 8 weeks. The development of structures that somewhat resemble NPs (which we will refer to as NPs) was confirmed by hematoxylin and eosin staining. The mRNA and protein levels of various inflammatory cell markers and mediators were measured by real-time PCR in nasal tissue and by ELISA in nasal lavage fluid (NLF), respectively. Total Ig isotype levels in NLF were also quantitated using the Mouse Ig Isotyping Multiplex kit (EMD Millipore, Billerica, MA) on a Luminex 200 instrument (Life Technologies, Grand Island, NY). Similar to human NPs, there were significant increases in gene expression of inflammatory cell markers, such as CD19, CD138, CD11c, and mast cell protease-6 in nasal tissue samples of the NP group compared with those of the control group. In further investigations of B cell activation, mRNA expressions of B cell activating factor and a proliferation-inducing ligand were found to be significantly increased in mouse NP tissue. B cell-activating factor protein concentration and IgA and IgG1 levels in NLF were significantly higher in the NP group compared with the control group. In this study, the NP mouse model demonstrated enhanced B cell responses, which are reminiscent of B cell responses in human NPs. PMID:27163839

  2. Early detectors of the heart's electrical activity.

    PubMed

    Breathnach, Caoimhghín S; Westphal, Wolfgang

    2006-04-01

    It was in Matteucci's rheoscopic frog in Pisa that evidence was first found for the electrical activity of the heart in 1844, and his results were confirmed and expanded 12 years later at Würzburg. The capillary electrometer gave a continuous record that could be photographed, and was used initially by Einthoven who, to obviate the onerous mathematical conversion of the electrometer record, developed the string galvanometer by the close of the century, and showed its clinical value in 1906. PMID:16650272

  3. Naturally occurring contaminants in the Piedmont and Blue Ridge crystalline-rock aquifers and Piedmont Early Mesozoic basin siliciclastic-rock aquifers, eastern United States, 1994–2008

    USGS Publications Warehouse

    Chapman, Melinda J.; Cravotta, Charles A.; Szabo, Zoltan; Lindsay, Bruce D.

    2013-01-01

    Groundwater quality and aquifer lithologies in the Piedmont and Blue Ridge Physiographic Provinces in the eastern United States vary widely as a result of complex geologic history. Bedrock composition (mineralogy) and geochemical conditions in the aquifer directly affect the occurrence (presence in rock and groundwater) and distribution (concentration and mobility) of potential naturally occurring contaminants, such as arsenic and radionuclides, in drinking water. To evaluate potential relations between aquifer lithology and the spatial distribution of naturally occurring contaminants, the crystalline-rock aquifers of the Piedmont and Blue Ridge Physiographic Provinces and the siliciclastic-rock aquifers of the Early Mesozoic basin of the Piedmont Physiographic Province were divided into 14 lithologic groups, each having from 1 to 16 lithochemical subgroups, based on primary rock type, mineralogy, and weathering potential. Groundwater-quality data collected by the U.S. Geological Survey (USGS) National Water-Quality Assessment (NAWQA) Program from 1994 through 2008 from 346 wells and springs in various hydrogeologic and land-use settings from Georgia through New Jersey were compiled and analyzed for this study. Analyses for most constituents were for filtered samples, and, thus, the compiled data consist largely of dissolved concentrations. Concentrations were compared to criteria for protection of human health, such as U.S. Environmental Protection Agency (USEPA) drinking water maximum contaminant levels and secondary maximum contaminant levels or health-based screening levels developed by the USGS NAWQA Program in cooperation with the USEPA, the New Jersey Department of Environmental Protection, and Oregon Health & Science University. Correlations among constituent concentrations, pH, and oxidation-reduction (redox) conditions were used to infer geochemical controls on constituent mobility within the aquifers. Of the 23 trace-element constituents evaluated

  4. Early spring sex differences in luteinizing hormone response to gonadotropin releasing hormone in co-occurring resident and migrant dark-eyed juncos (Junco hyemalis).

    PubMed

    Greives, Timothy J; Fudickar, Adam M; Atwell, Jonathan W; Meddle, Simone L; Ketterson, Ellen D

    2016-09-15

    To optimally time reproduction, animals must coordinate changes in the hypothalamo-pituitary-gonadal (HPG) axis. The extent of intra-species variation in seasonal timing of reproductive function is considerable, both within and among populations. Dark-eyed junco (Junco hyemalis) populations are known to differ in their reproductive timing response to cues experienced in the same habitat in late winter/early spring. Specifically in juncos cohabitating on shared wintering grounds, residents initiate breeding and reproductive activity but migrants delay reproductive development and prepare to migrate before breeding. Here, we test the hypothesis that the pituitary gland acts as a 'control point' to modulate differential HPG axis activity across populations. We sampled free-living resident and migrant juncos on their shared over-wintering grounds in March, thus all individuals were experiencing the same environmental cues, including photoperiod. We predicted that during this critical time of transition, residents would more readily respond to repeated gonadotropin releasing hormone (GnRH) stimulation with increases in luteinizing hormone (LH), in contrast to migrants, which should delay full reproductive activity. Our data indicate that migrant females, while still on the overwintering grounds, have a reduced LH response to repeated GnRH injections compared to resident females. Male migrant and resident birds did not differ in their responsiveness to repeated GnRH. Our results suggest a sex difference in the costs of mistimed activation of the HPG axis, with female migrants being less responsive than residents females and males to repeated stimulation. Further, our data implicate a key role for the pituitary in regulating appropriate reproductive timing responses. PMID:27374492

  5. Naturally occurring contaminants in the Piedmont and Blue Ridge crystalline-rock aquifers and Piedmont Early Mesozoic basin siliciclastic-rock aquifers, eastern United States, 1994–2008

    USGS Publications Warehouse

    Chapman, Melinda J.; Cravotta, Charles A.; Szabo, Zoltan; Lindsay, Bruce D.

    2013-01-01

    Groundwater quality and aquifer lithologies in the Piedmont and Blue Ridge Physiographic Provinces in the eastern United States vary widely as a result of complex geologic history. Bedrock composition (mineralogy) and geochemical conditions in the aquifer directly affect the occurrence (presence in rock and groundwater) and distribution (concentration and mobility) of potential naturally occurring contaminants, such as arsenic and radionuclides, in drinking water. To evaluate potential relations between aquifer lithology and the spatial distribution of naturally occurring contaminants, the crystalline-rock aquifers of the Piedmont and Blue Ridge Physiographic Provinces and the siliciclastic-rock aquifers of the Early Mesozoic basin of the Piedmont Physiographic Province were divided into 14 lithologic groups, each having from 1 to 16 lithochemical subgroups, based on primary rock type, mineralogy, and weathering potential. Groundwater-quality data collected by the U.S. Geological Survey (USGS) National Water-Quality Assessment (NAWQA) Program from 1994 through 2008 from 346 wells and springs in various hydrogeologic and land-use settings from Georgia through New Jersey were compiled and analyzed for this study. Analyses for most constituents were for filtered samples, and, thus, the compiled data consist largely of dissolved concentrations. Concentrations were compared to criteria for protection of human health, such as U.S. Environmental Protection Agency (USEPA) drinking water maximum contaminant levels and secondary maximum contaminant levels or health-based screening levels developed by the USGS NAWQA Program in cooperation with the USEPA, the New Jersey Department of Environmental Protection, and Oregon Health & Science University. Correlations among constituent concentrations, pH, and oxidation-reduction (redox) conditions were used to infer geochemical controls on constituent mobility within the aquifers. Of the 23 trace-element constituents evaluated

  6. 50+ Activities for Early Childhood Essential Elements. Volume II.

    ERIC Educational Resources Information Center

    Education Service Center Region 6, Huntsville, TX.

    Written as a companion resource to "Early Childhood Essential Elements," a document developed by the Education Service Center, Region VI, Huntsville, Texas, this second volume of a two-volume activity guide provides activities enhancing children's self-help, social/emotional, and creative/expressive skills. The guide also provides a short…

  7. Fall Activities for the Early Childhood and Special Education Classroom.

    ERIC Educational Resources Information Center

    Denton, Penny

    Designed for teachers of early childhood or special education students, this guide contains instructions and illustrations for classroom activities for the months of September, October, and November. Most of the activities involve art projects and many incorporate teaching in other subject areas such as mathematics, language arts, science, and…

  8. Sports, Physical Activity and Recreation in Early American History.

    ERIC Educational Resources Information Center

    Ballou, Ralph B.

    Sports and physical recreation activities have been part of American life since the days of the early settlers. Although the settlers were faced with problems of survival, accounts of life in the colonies in the 1600's carry mention of bowling in the streets, play with bows and arrows, and ice skating. Other activities to gain popularity before…

  9. K-ras activation occurs frequently in mucinous adenocarcinomas and rarely in other common epithelial tumors of the human ovary.

    PubMed Central

    Enomoto, T.; Weghorst, C. M.; Inoue, M.; Tanizawa, O.; Rice, J. M.

    1991-01-01

    To explore the role of mutational activation of members of the ras family of cellular protooncogenes in the development of human ovarian neoplasms, a series of 37 ovarian tumors from Japanese patients was studied. These included 30 common epithelial tumors (1 mucinous tumor of borderline malignancy, 7 mucinous adenocarcinomas, and 22 nonmucinous carcinomas: 10 serous, 3 clear cell, 8 endometrioid, and 1 undifferentiated), 5 tumors of germ cell origin, and 2 sex cord/stromal cell tumors. Polymerase chain reaction was performed from selected areas of deparaffinized sections of formalin-fixed paraffin-embedded tissue, and the presence of activating point mutations in codons 12, 13, and 61 of the H-, N-, and K-ras genes was probed by dot-blot hybridization analysis with mutation specific oligonucleotides. Mutations in K-ras were also looked for by direct genomic sequencing. The overall frequency of ras gene mutations was 10/37 (27%). Mutations were detected only in K-ras, and were found in most of the mucinous tumors, including the one such tumor of borderline malignancy (6/8; 75%). In one mucinous adenocarcinoma, two mutations were detected in paraffin-embedded material that had not previously been found in high molecular weight DNA isolated from frozen tissue from the same case. K-ras mutations occurred significantly more frequently in mucinous tumors (6/8, 75%) than in serous carcinomas (2/10, 20%; P = 0.031) or in all nonmucinous types of epithelial ovarian tumors combined (3/22, 14%; P = 0.0031). Images Figure 1 Figure 2 PMID:1656759

  10. Expression of a naturally occurring angiotensin AT1 receptor cleavage fragment elicits caspase-activation and apoptosis

    PubMed Central

    Singh, Akannsha; deHaro, Dawn; Alam, Jawed; Re, Richard N.

    2011-01-01

    Several transmembrane receptors are documented to accumulate in nuclei, some as holoreceptors and others as cleaved receptor products. Our prior studies indicate that a population of the 7-transmembrane angiotensin type-1 receptor (AT1R) is cleaved in a ligand-augmented manner after which the cytoplasmic, carboxy-terminal cleavage fragment (CF) traffics to the nucleus. In the present report, we determine the precise cleavage site within the AT1R by mass spectrometry and Edman sequencing. Cleavage occurs between Leu(305) and Gly(306) at the junction of the seventh transmembrane domain and the intracellular cytoplasmic carboxy-terminal domain. To evaluate the function of the CF distinct from the holoreceptor, we generated a construct encoding the CF as an in-frame yellow fluorescent protein fusion. The CF accumulates in nuclei and induces apoptosis in CHO-K1 cells, rat aortic smooth muscle cells (RASMCs), MCF-7 human breast adenocarcinoma cells, and H9c2 rat cardiomyoblasts. All cell types show nuclear fragmentation and disintegration, as well as evidence for phosphotidylserine displacement in the plasma membrane and activated caspases. RASMCs specifically showed a 5.2-fold increase (P < 0.001) in CF-induced active caspases compared with control and a 7.2-fold increase (P < 0.001) in cleaved caspase-3 (Asp174). Poly(ADP-ribose)polymerase was upregulated 4.8-fold (P < 0.001) in CF expressing cardiomyoblasts and colocalized with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). CF expression also induces DNA laddering, the gold-standard for apoptosis in all cell types studied. CF-induced apoptosis, therefore, appears to be a general phenomenon as it is observed in multiple cell types including smooth muscle cells and cardiomyoblasts. PMID:21813711

  11. Expression of a naturally occurring angiotensin AT(1) receptor cleavage fragment elicits caspase-activation and apoptosis.

    PubMed

    Cook, Julia L; Singh, Akannsha; DeHaro, Dawn; Alam, Jawed; Re, Richard N

    2011-11-01

    Several transmembrane receptors are documented to accumulate in nuclei, some as holoreceptors and others as cleaved receptor products. Our prior studies indicate that a population of the 7-transmembrane angiotensin type-1 receptor (AT(1)R) is cleaved in a ligand-augmented manner after which the cytoplasmic, carboxy-terminal cleavage fragment (CF) traffics to the nucleus. In the present report, we determine the precise cleavage site within the AT(1)R by mass spectrometry and Edman sequencing. Cleavage occurs between Leu(305) and Gly(306) at the junction of the seventh transmembrane domain and the intracellular cytoplasmic carboxy-terminal domain. To evaluate the function of the CF distinct from the holoreceptor, we generated a construct encoding the CF as an in-frame yellow fluorescent protein fusion. The CF accumulates in nuclei and induces apoptosis in CHO-K1 cells, rat aortic smooth muscle cells (RASMCs), MCF-7 human breast adenocarcinoma cells, and H9c2 rat cardiomyoblasts. All cell types show nuclear fragmentation and disintegration, as well as evidence for phosphotidylserine displacement in the plasma membrane and activated caspases. RASMCs specifically showed a 5.2-fold increase (P < 0.001) in CF-induced active caspases compared with control and a 7.2-fold increase (P < 0.001) in cleaved caspase-3 (Asp174). Poly(ADP-ribose)polymerase was upregulated 4.8-fold (P < 0.001) in CF expressing cardiomyoblasts and colocalized with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). CF expression also induces DNA laddering, the gold-standard for apoptosis in all cell types studied. CF-induced apoptosis, therefore, appears to be a general phenomenon as it is observed in multiple cell types including smooth muscle cells and cardiomyoblasts.

  12. Influence of naturally occurring dissolved organic matter, colloids, and cations on nanofiltration of pharmaceutically active and endocrine disrupting compounds.

    PubMed

    Sadmani, A H M Anwar; Andrews, Robert C; Bagley, David M

    2014-12-01

    This study examined the rejection of selected pharmaceutically active (PhAC) and endocrine disrupting compounds (EDCs) when using nanofiltration as a function of naturally occurring dissolved organic matter (DOM), colloidal particles, cations and their interactions. Lake Ontario water served as a source of natural DOM and colloidal particles. PhAC/EDC rejection experiments were conducted using raw Lake Ontario water and Lake Ontario water that was pre-treated with either ultrafiltration to remove colloidal particles, or fluidized ion exchange resins to remove DOM. Additionally, the concentration of cations (Ca(2+), Mg(2+), and Na(+)) in the raw and pre-treated water matrices was varied. While ionic PhACs and EDCs exhibited high rejections from all the water matrices examined, neutral compounds were most effectively rejected in water containing DOM and no colloids, and least effectively rejected from colloid-containing water with increased cations but no DOM. The presence of DOM significantly improved compound rejection and the increase in cation concentration significantly decreased rejection. The presence of colloids had comparatively little effect except to mitigate the impact of increased cation concentration, apparently providing some cation-buffering capacity. The sequence in which constituents are removed from waters during treatment may significantly impact PhAC and EDC removal, especially of neutral compounds.

  13. Effects of Isoflavones and Amino Acid Therapies for Hot Flashes and Co-occurring Symptoms during the Menopausal Transition and Early Post Menopause: A Systematic Review

    PubMed Central

    Thomas, Annette; Ismail, Rita; Taylor-Swanson, Lisa; Cray, Lori; Schnall, Janet G.; Mitchell, Ellen Sullivan; Woods, Nancy Fugate

    2014-01-01

    Aims Review controlled clinical trials of isoflavones and amino acid preparation effects on hot flashes and at least one other symptom including mood, sleep, pain, and cognitive function that women report during the menopausal transition and early postmenopause. Methods An experienced reference librarian searched PubMed/Medline, CINAHL Plus, PsycInfo, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science, EMBASE, AMED, and Alt-Health Watch for English-language randomized controlled trials between 2004 to July 2011. Seventeen trials of isoflavones and amino acid effects on hot flashes and one additional symptom were identified. Results In five trials of soy isoflavone preparations, two (6g soy germ extract and 25g soy protein in soy nuts) significantly decreased hot flashes, but no other symptoms. In the seven trials of other isoflavones, six significantly reduced hot flashes; in addition, Red Clover (80 mg) significantly reduced mood symptoms; Rexflavone (350 mg) for women with Kupperman Index > 20 significantly reduced sleep symptoms; two trials had significant reductions for pain: Isoflavone powder (90 mg) and Red Clover (80 mg). The only trial in this systematic review that significantly reduced cognitive symptoms was Red Clover (80 mg). In one trial, Red Clover isoflavone (80 mg/d) significantly relieved hot flashes, mood, pain, and cognitive symptoms. Amino acids yielded no significant results. Equol supplements of 30 mg/d for non-Equol producing women significantly reduced mood symptoms in one trial. The Magnolia Bark Extract combination significantly reduced hot flashes, mood, and sleep symptoms. Conclusions Isoflavone trials yielded significant reductions on hot flashes and co-occurring symptoms during the menopausal transition and postmenopause, but studies require replication with larger sample sizes and attention to measurement of outcomes. PMID:24951101

  14. Laser Doppler flowmetry: an early diagnosis instrument in detecting the soft tissue changes that occur during radiotherapy to the head and neck area, clinical case report

    NASA Astrophysics Data System (ADS)

    Petre, L. C.; Miron, M. I.; Ianes, E.

    2016-03-01

    Aim of the study: Our goal was to monitor soft tissue changes occurring during radiotherapy - both through clinical examination and using LDF - in order to establish Laser Doppler as an early diagnosis instrument in this situation, and also to assess what kind of dental procedures could be provided during radiotherapy, in order to increase patients' quality of life. Material and Method: Our study included two male patients, who received head and neck radiotherapy. Patient A, 68 years old, underwent 31 radiotherapy exposures. Patient B, 52 years old, underwent 24 exposures. They received a thorough clinical examination, and a LDF evaluation of gingival blood flow in areas close to the irradiated site, after the first, the 18th, and the last radiotherapy exposure. Results: Patient A presented radiotherapy induced mucositis, after the 18th radiotherapy exposure. After the last exposure the mucositis worsened, additionally, radiodermitis appeared on the neck. LDF showed an increase in blood flow of the irradiated area, even after the first exposure, and it persisted throughout treatment. Patient B showed no clinical changes, besides a hyperkeratinisation of the gingiva in the irradiated area, after the last exposure. LDF showed an overall increase in vascularity of the area throughout treatment. Discussion: Even after the first radiotherapy exposure, and also when clinical changes were not apparent, LDF measurements revealed an increase in blood flow in the gingiva of irradiated patients. LDF might allow us to establish the most appropriate moment in time for each dental treatment, in order to increase the quality of life.

  15. Early development of synchrony in cortical activations in the human

    PubMed Central

    Koolen, N.; Dereymaeker, A.; Räsänen, O.; Jansen, K.; Vervisch, J.; Matic, V.; Naulaers, G.; De Vos, M.; Van Huffel, S.; Vanhatalo, S.

    2016-01-01

    Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44 weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates. PMID:26876605

  16. Early microglia activation in a mouse model of chronic glaucoma

    PubMed Central

    Bosco, Alejandra; Steele, Michael R.; Vetter, Monica L.

    2014-01-01

    Changes in microglial cell activation and distribution are associated with neuronal decline in the CNS, particularly under pathological conditions. Activated microglia converge on the initial site of axonal degeneration in human glaucoma, yet, their part in its pathophysiology remains unresolved. To begin with, it is unknown whether microglia activation precedes or is a late consequence of retinal ganglion cell (RGC) neurodegeneration. Here, we address this critical element in DBA/2J (D2) mice, an established model of chronic inherited glaucoma, using as a control the congenic substrain DBA/2J Gpnmb+/SjJ (D2G), which is not affected by glaucoma. We analyzed the spatial distribution and timecourse of microglial changes in the retina, as well as within the proximal optic nerve prior to and throughout ages when neurodegeneration has been reported. Exclusively in D2 mice, we detected early microglia clustering in the inner central retina and unmyelinated optic nerve regions, with microglia activation peaking by 3 months of age. Between 5 and 8 months of age, activated microglia persisted and concentrated in the optic disc, but also localized to the retinal periphery. Collectively, our findings suggest microglia activation is an early alteration in the retina and optic nerve in D2 glaucoma, potentially contributing to disease onset or progression. Ultimately, detection of microglial activation may have value in early disease diagnosis, while modulation of microglial responses may alter disease progression. PMID:21246546

  17. Pathogenic Triad in Bacterial Meningitis: Pathogen Invasion, NF-κB Activation, and Leukocyte Transmigration that Occur at the Blood-Brain Barrier

    PubMed Central

    Wang, Shifu; Peng, Liang; Gai, Zhongtao; Zhang, Lehai; Jong, Ambrose; Cao, Hong; Huang, Sheng-He

    2016-01-01

    Bacterial meningitis remains the leading cause of disabilities worldwide. This life-threatening disease has a high mortality rate despite the availability of antibiotics and improved critical care. The interactions between bacterial surface components and host defense systems that initiate bacterial meningitis have been studied in molecular and cellular detail over the past several decades. Bacterial meningitis commonly exhibits triad hallmark features (THFs): pathogen penetration, nuclear factor-kappaB (NF-κB) activation in coordination with type 1 interferon (IFN) signaling and leukocyte transmigration that occur at the blood-brain barrier (BBB), which consists mainly of brain microvascular endothelial cells (BMEC). This review outlines the progression of these early inter-correlated events contributing to the central nervous system (CNS) inflammation and injury during the pathogenesis of bacterial meningitis. A better understanding of these issues is not only imperative to elucidating the pathogenic mechanism of bacterial meningitis, but may also provide the in-depth insight into the development of novel therapeutic interventions against this disease. PMID:26925035

  18. Pathogenic Triad in Bacterial Meningitis: Pathogen Invasion, NF-κB Activation, and Leukocyte Transmigration that Occur at the Blood-Brain Barrier.

    PubMed

    Wang, Shifu; Peng, Liang; Gai, Zhongtao; Zhang, Lehai; Jong, Ambrose; Cao, Hong; Huang, Sheng-He

    2016-01-01

    Bacterial meningitis remains the leading cause of disabilities worldwide. This life-threatening disease has a high mortality rate despite the availability of antibiotics and improved critical care. The interactions between bacterial surface components and host defense systems that initiate bacterial meningitis have been studied in molecular and cellular detail over the past several decades. Bacterial meningitis commonly exhibits triad hallmark features (THFs): pathogen penetration, nuclear factor-kappaB (NF-κB) activation in coordination with type 1 interferon (IFN) signaling and leukocyte transmigration that occur at the blood-brain barrier (BBB), which consists mainly of brain microvascular endothelial cells (BMEC). This review outlines the progression of these early inter-correlated events contributing to the central nervous system (CNS) inflammation and injury during the pathogenesis of bacterial meningitis. A better understanding of these issues is not only imperative to elucidating the pathogenic mechanism of bacterial meningitis, but may also provide the in-depth insight into the development of novel therapeutic interventions against this disease.

  19. Natural Killer Activity: Early Days, Advances, and Seminal Observations

    PubMed Central

    Ortaldo, John R.; Wiltrout, Robert H.; Reynolds, Craig W.

    2014-01-01

    This manuscript describes the early history of NK cell discovery, with emphasis on the events in the first decade of NK cell studies, 1972–1982. The authors highlight some of the earliest and most important observations that would later prove to be milestones in the study of NK cells and their activity. PMID:24941370

  20. Analytical Validation of Telomerase Activity for Cancer Early Detection

    PubMed Central

    Jakupciak, John P.; Wang, Wendy; Barker, Peter E.; Srivastava, Sudhir; Atha, Donald H.

    2004-01-01

    Activation of telomerase plays a critical role in unlimited proliferation and immortalization of cells. Telomerase activity has been shown to correlate with tumor progression, indicating that tumors expressing this enzyme possess aggressive clinical behavior and that telomerase activity may be a useful biomarker for early detection of cancer. However, measurements of telomerase activity by current methods such as telomeric repeat amplification protocol (TRAP)/polymerase chain reaction (PCR) or antibody-based radioimmunoassay (RIA) are low-throughput and not robust enough to easily accommodate the required statistical analysis to determine whether telomerase activity is a practical biomarker. As part of the National Cancer Institute Early Detection Research Network of analytical validation, we have developed a robot assisted TRAP assay (RApidTRAP) of telomerase, a potential biomarker for cancer early detection. Measurements of human telomerase reverse transcriptase catalytic subunit (hTERT) mRNA were performed in concert with measurement of telomerase activity. For this purpose we determined hTERT mRNA concentration and telomerase activity in human normal (RPE-28) and cancer (A549) cell lines as well as in human serum (SRM 1951A). Telomerase activity measurements were made using the TRAP/PCR capillary electrophoresis (CE) method on (50 to 1000) cells/reaction isolated from cell extracts. Measurement of hTERT mRNA was made using specific primers and probes on a LightCycler in the range of (10 to 7000) cells/reaction. Comparison of high-throughput telomerase activity measurements using the robot and those performed manually were consistent in sensitivity and reproducibility. Using this combination of telomerase activity and hTERT mRNA measurements, the automated system improved efficiency over traditional TRAP/PCR methods. PMID:15269291

  1. Early activation of caspases during T lymphocyte stimulation results in selective substrate cleavage in nonapoptotic cells.

    PubMed

    Alam, A; Cohen, L Y; Aouad, S; Sékaly, R P

    1999-12-20

    Apoptosis induced by T cell receptor (TCR) triggering in T lymphocytes involves activation of cysteine proteases of the caspase family through their proteolytic processing. Caspase-3 cleavage was also reported during T cell stimulation in the absence of apoptosis, although the physiological relevance of this response remains unclear. We show here that the caspase inhibitor benzyloxycarbonyl (Cbz)-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD) blocks proliferation, major histocompatibility complex class II expression, and blastic transformation during stimulation of peripheral blood lymphocytes. Moreover, T cell activation triggers the selective processing and activation of downstream caspases (caspase-3, -6, and -7), but not caspase-1, -2, or -4, as demonstrated even in intact cells using a cell-permeable fluorescent substrate. Caspase-3 processing occurs in different T cell subsets (CD4(+), CD8(+), CD45RA(+), and CD45RO(+)), and in activated B lymphocytes. The pathway leading to caspase activation involves death receptors and caspase-8, which is also processed after TCR triggering, but not caspase-9, which remains as a proenzyme. Most importantly, caspase activity results in a selective substrate specificity, since poly(ADP-ribose) polymerase (PARP), lamin B, and Wee1 kinase, but not DNA fragmentation factor (DFF45) or replication factor C (RFC140), are processed. Caspase and substrate processing occur in nonapoptotic lymphocytes. Thus, caspase activation is an early and physiological response in viable, stimulated lymphocytes, and appears to be involved in early steps of lymphocyte activation. PMID:10601362

  2. Cross-modal activation of auditory regions during visuo-spatial working memory in early deafness.

    PubMed

    Ding, Hao; Qin, Wen; Liang, Meng; Ming, Dong; Wan, Baikun; Li, Qiang; Yu, Chunshui

    2015-09-01

    Early deafness can reshape deprived auditory regions to enable the processing of signals from the remaining intact sensory modalities. Cross-modal activation has been observed in auditory regions during non-auditory tasks in early deaf subjects. In hearing subjects, visual working memory can evoke activation of the visual cortex, which further contributes to behavioural performance. In early deaf subjects, however, whether and how auditory regions participate in visual working memory remains unclear. We hypothesized that auditory regions may be involved in visual working memory processing and activation of auditory regions may contribute to the superior behavioural performance of early deaf subjects. In this study, 41 early deaf subjects (22 females and 19 males, age range: 20-26 years, age of onset of deafness < 2 years) and 40 age- and gender-matched hearing controls underwent functional magnetic resonance imaging during a visuo-spatial delayed recognition task that consisted of encoding, maintenance and recognition stages. The early deaf subjects exhibited faster reaction times on the spatial working memory task than did the hearing controls. Compared with hearing controls, deaf subjects exhibited increased activation in the superior temporal gyrus bilaterally during the recognition stage. This increased activation amplitude predicted faster and more accurate working memory performance in deaf subjects. Deaf subjects also had increased activation in the superior temporal gyrus bilaterally during the maintenance stage and in the right superior temporal gyrus during the encoding stage. These increased activation amplitude also predicted faster reaction times on the spatial working memory task in deaf subjects. These findings suggest that cross-modal plasticity occurs in auditory association areas in early deaf subjects. These areas are involved in visuo-spatial working memory. Furthermore, amplitudes of cross-modal activation during the maintenance stage were

  3. Control of activation of liver RNA polymerase I occurring after re-feeding of protein-depleted mice.

    PubMed Central

    Haim, L; Iapalucci-Espinoza, S; Conde, R; Franze-Fernández, M T

    1983-01-01

    Shortly after feeding protein-depleted mice with a meal containing protein, the RNA polymerase I activity in isolated liver nuclei shows a 2-fold increase over the values in the nuclei of either normal or protein-depleted mice. The activity of the RNA polymerase I solubilized from nuclei of re-fed mice was slightly enhanced, probably reflecting an increase in enzyme amount. However, this increase only accounts for about 30% of the stimulation of transcription in the intact nuclei. Administration of pactamycin, an inhibitor of protein synthesis, to normal or protein-depleted mice has almost no inhibitory effect on the RNA polymerase I activity in the isolated nuclei. On the contrary, within 15 min after treatment with the drug, the stimulated activity in nuclei from re-fed mice declines towards the values in normal or protein-depleted mice and then remains constant. The activity of the solubilized enzyme remains slightly elevated for at least 2 1/2 h after re-fed mice are treated with pactamycin. These observations indicate that the stimulation of the RNA polymerase I activity in the intact nuclei after re-feeding is controlled by mechanisms other than an increase in the enzyme amount and suggest the presence of short-lived proteins required for inducing an activated state of transcription. PMID:6870809

  4. T-cell activation and early gene response in dogs.

    PubMed

    Mortlock, Sally-Anne; Wei, Jerry; Williamson, Peter

    2015-01-01

    T-cells play a crucial role in canine immunoregulation and defence against invading pathogens. Proliferation is fundamental to T-cell differentiation, homeostasis and immune response. Initiation of proliferation following receptor mediated stimuli requires a temporally programmed gene response that can be identified as immediate-early, mid- and late phases. The immediate-early response genes in T-cell activation engage the cell cycle machinery and promote subsequent gene activation events. Genes involved in this immediate-early response in dogs are yet to be identified. The present study was undertaken to characterise the early T-cell gene response in dogs to improve understanding of the genetic mechanisms regulating immune function. Gene expression profiles were characterised using canine gene expression microarrays and quantitative reverse transcription PCR (qRT-PCR), and paired samples from eleven dogs. Significant functional annotation clusters were identified following stimulation with phytohemagluttinin (PHA) (5μg/ml), including the Toll-like receptor signaling pathway and phosphorylation pathways. Using strict statistical criteria, 13 individual genes were found to be differentially expressed, nine of which have ontologies that relate to proliferation and cell cycle control. These included, prostaglandin-endoperoxide synthase 2 (PTGS2/COX2), early growth response 1 (EGR1), growth arrest and DNA damage-inducible gene (GADD45B), phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1), V-FOS FBJ murine osteosarcoma viral oncogene homolog (FOS), early growth response 2 (EGR2), hemogen (HEMGN), polo-like kinase 2 (PLK2) and polo-like kinase 3 (PLK3). Differential gene expression was re-examined using qRT-PCR, which confirmed that EGR1, EGR2, PMAIP1, PTGS2, FOS and GADD45B were significantly upregulated in stimulated cells and ALAS2 downregulated. PTGS2 and EGR1 showed the highest levels of response in these dogs. Both of these genes are involved in cell cycle

  5. Inhibition of lysine acetyltransferase KAT3B/p300 activity by a naturally occurring hydroxynaphthoquinone, plumbagin.

    PubMed

    Ravindra, Kodihalli C; Selvi, B Ruthrotha; Arif, Mohammed; Reddy, B A Ashok; Thanuja, Gali R; Agrawal, Shipra; Pradhan, Suman Kalyan; Nagashayana, Natesh; Dasgupta, Dipak; Kundu, Tapas K

    2009-09-01

    Lysine acetyltransferases (KATs), p300 (KAT3B), and its close homologue CREB-binding protein (KAT3A) are probably the most widely studied KATs with well documented roles in various cellular processes. Hence, the dysfunction of p300 may result in the dysregulation of gene expression leading to the manifestation of many disorders. The acetyltransferase activity of p300/CREB-binding protein is therefore considered as a target for new generation therapeutics. We describe here a natural compound, plumbagin (RTK1), isolated from Plumbago rosea root extract, that inhibits histone acetyltransferase activity potently in vivo. Interestingly, RTK1 specifically inhibits the p300-mediated acetylation of p53 but not the acetylation by another acetyltransferase, p300/CREB-binding protein -associated factor, PCAF, in vivo. RTK1 inhibits p300 histone acetyltransferase activity in a noncompetitive manner. Docking studies and site-directed mutagenesis of the p300 histone acetyltransferase domain suggest that a single hydroxyl group of RTK1 makes a hydrogen bond with the lysine 1358 residue of this domain. In agreement with this, we found that indeed the hydroxyl group-substituted plumbagin derivatives lost the acetyltransferase inhibitory activity. This study describes for the first time the chemical entity (hydroxyl group) required for the inhibition of acetyltransferase activity.

  6. GATA Factor Regulation in Excess Nitrogen Occurs Independently of Gtr-Ego Complex-Dependent TorC1 Activation.

    PubMed

    Tate, Jennifer J; Georis, Isabelle; Rai, Rajendra; Vierendeels, Fabienne; Dubois, Evelyne; Cooper, Terrance G

    2015-05-29

    The TorC1 protein kinase complex is a central component in a eukaryotic cell's response to varying nitrogen availability, with kinase activity being stimulated in nitrogen excess by increased intracellular leucine. This leucine-dependent TorC1 activation requires functional Gtr1/2 and Ego1/3 complexes. Rapamycin inhibition of TorC1 elicits nuclear localization of Gln3, a GATA-family transcription activator responsible for the expression of genes encoding proteins required to transport and degrade poor nitrogen sources, e.g., proline. In nitrogen-replete conditions, Gln3 is cytoplasmic and Gln3-mediated transcription minimal, whereas in nitrogen limiting or starvation conditions, or after rapamycin treatment, Gln3 is nuclear and transcription greatly increased. Increasing evidence supports the idea that TorC1 activation may not be as central to nitrogen-responsive intracellular Gln3 localization as envisioned previously. To test this idea directly, we determined whether Gtr1/2- and Ego1/3-dependent TorC1 activation also was required for cytoplasmic Gln3 sequestration and repressed GATA factor-mediated transcription by abolishing the Gtr-Ego complex proteins. We show that Gln3 is sequestered in the cytoplasm of gtr1Δ, gtr2Δ, ego1Δ, and ego3Δ strains either long term in logarithmically glutamine-grown cells or short term after refeeding glutamine to nitrogen-limited or -starved cells; GATA factor-dependent transcription also was minimal. However, in all but a gtr1Δ, nuclear Gln3 localization in response to nitrogen limitation or starvation was adversely affected. Our data demonstrate: (i) Gtr-Ego-dependent TorC1 activation is not required for cytoplasmic Gln3 sequestration in nitrogen-rich conditions; (ii) a novel Gtr-Ego-TorC1 activation-independent mechanism sequesters Gln3 in the cytoplasm; (iii) Gtr and Ego complex proteins participate in nuclear Gln3-Myc(13) localization, heretofore unrecognized functions for these proteins; and (iv) the importance of

  7. A VIN1 GUS::GFP fusion reveals activated sucrose metabolism programming occurring in interspersed cells during tomato fruit ripening.

    PubMed

    Estornell, Leandro Hueso; Pons, Clara; Martínez, Alicia; O'Connor, José Enrique; Orzaez, Diego; Granell, Antonio

    2013-08-15

    The tomato is a model for fleshy fruit development and ripening. Here we report on the identification of a novel unique cell autonomous/cellular pattern of expression that was detected in fruits of transgenic tomato lines carrying a GFP GUS driven by the fruit specific vacuolar invertase promoter VIN1. The VIN1 promoter sequence faithfully reproduced the global endogenous VIN expression by conferring a biphasic pattern of expression with a second phase clearly associated to fruit ripening. A closer view revealed a salt and pepper pattern of expression characterized by individual cells exhibiting a range of expression levels (from high to low) surrounded by cells with no expression. This type of pattern was detected across different fruit tissues and cell types with some preferences for vascular, sub-epidermal layer and the inner part of the fruit. Cell ability to show promoter activity was neither directly associated with overall ripening - as we find VIN+ and - VIN- cells at all stages of ripening, nor with cell size. Nevertheless the number of cells with active VIN-driven expression increased with ripening and the activity of the VIN promoter seems to be inversely correlated with cell size in VIN+ cells. Gene expression analysis of FACS-sorted VIN+ cells revealed a transcriptionally distinct subpopulation of cells defined by increased expression of genes related to sucrose metabolism, and decreased activity in protein synthesis and chromatin remodeling. This finding suggests that local micro heterogeneity may underlie some aspects (i.e. the futile cycles involving sucrose metabolism) of an otherwise more uniform looking ripening program.

  8. Mitogen-activated protein kinase is required for the behavioural desensitization that occurs after repeated injections of angiotensin II.

    PubMed

    Vento, Peter J; Daniels, Derek

    2012-12-01

    Angiotensin II (Ang II) acts on central angiotensin type 1 (AT(1)) receptors to increase water and saline intake. Prolonged exposure to Ang II in cell culture models results in a desensitization of the AT(1) receptor that is thought to involve receptor internalization, and a behavioural correlate of this desensitization has been shown in rats after repeated central injections of Ang II. Specifically, rats given repeated injections of Ang II drink less water than control animals after a subsequent test injection of Ang II. In the same conditions, however, repeated injections of Ang II have no effect on Ang II-induced saline intake. Given earlier studies indicating that separate intracellular signalling pathways mediate Ang II-induced water and saline intake, we hypothesized that the desensitization observed in rats may be incomplete, leaving the receptor able to activate mitogen-activated protein (MAP) kinases (ERK1/2), which play a role in Ang II-induced saline intake without affecting water intake. In support of this hypothesis, we found no difference in MAP kinase phosphorylation after an Ang II test injection in rats given prior treatment with repeated injections of vehicle, Ang II or Sar(1),Ile(4),Ile(8)-Ang II (SII), an Ang II analogue that activates MAP kinase without G protein coupling. In addition, we found that pretreatment with the MAP kinase inhibitor U0126 completely blocked the desensitizing effect of repeated Ang II injections on water intake. Furthermore, Ang II-induced water intake was reduced to a similar extent by repeated injections of Ang II or SII. The results suggest that G protein-independent signalling is sufficient to produce behavioural desensitization of the angiotensin system and that the desensitization requires MAP kinase activation.

  9. Activation and Desensitization of Peripheral Muscle and Neuronal Nicotinic Acetylcholine Receptors by Selected, Naturally-Occurring Pyridine Alkaloids.

    PubMed

    Green, Benedict T; Lee, Stephen T; Welch, Kevin D; Cook, Daniel; Kem, William R

    2016-07-04

    Teratogenic alkaloids can cause developmental defects due to the inhibition of fetal movement that results from desensitization of fetal muscle-type nicotinic acetylcholine receptors (nAChRs). We investigated the ability of two known teratogens, the piperidinyl-pyridine anabasine and its 1,2-dehydropiperidinyl analog anabaseine, to activate and desensitize peripheral nAChRs expressed in TE-671 and SH-SY5Y cells. Activation-concentration response curves for each alkaloid were obtained in the same multi-well plate. To measure rapid desensitization, cells were first exposed to five potentially-desensitizing concentrations of each alkaloid in log10 molar increments from 10 nM to 100 µM and then to a fixed concentration of acetylcholine (ACh), which alone produces near-maximal activation. The fifty percent desensitization concentration (DC50) was calculated from the alkaloid concentration-ACh response curve. Agonist fast desensitization potency was predicted by the agonist potency measured in the initial response. Anabaseine was a more potent desensitizer than anabasine. Relative to anabaseine, nicotine was more potent to autonomic nAChRs, but less potent to the fetal neuromuscular nAChRs. Our experiments have demonstrated that anabaseine is more effective at desensitizing fetal muscle-type nAChRs than anabasine or nicotine and, thus, it is predicted to be more teratogenic.

  10. Activation and Desensitization of Peripheral Muscle and Neuronal Nicotinic Acetylcholine Receptors by Selected, Naturally-Occurring Pyridine Alkaloids

    PubMed Central

    Green, Benedict T.; Lee, Stephen T.; Welch, Kevin D.; Cook, Daniel; Kem, William R.

    2016-01-01

    Teratogenic alkaloids can cause developmental defects due to the inhibition of fetal movement that results from desensitization of fetal muscle-type nicotinic acetylcholine receptors (nAChRs). We investigated the ability of two known teratogens, the piperidinyl-pyridine anabasine and its 1,2-dehydropiperidinyl analog anabaseine, to activate and desensitize peripheral nAChRs expressed in TE-671 and SH-SY5Y cells. Activation-concentration response curves for each alkaloid were obtained in the same multi-well plate. To measure rapid desensitization, cells were first exposed to five potentially-desensitizing concentrations of each alkaloid in log10 molar increments from 10 nM to 100 µM and then to a fixed concentration of acetylcholine (ACh), which alone produces near-maximal activation. The fifty percent desensitization concentration (DC50) was calculated from the alkaloid concentration-ACh response curve. Agonist fast desensitization potency was predicted by the agonist potency measured in the initial response. Anabaseine was a more potent desensitizer than anabasine. Relative to anabaseine, nicotine was more potent to autonomic nAChRs, but less potent to the fetal neuromuscular nAChRs. Our experiments have demonstrated that anabaseine is more effective at desensitizing fetal muscle-type nAChRs than anabasine or nicotine and, thus, it is predicted to be more teratogenic. PMID:27384586

  11. Activation and Inhibition of the Receptor Histidine Kinase AgrC Occurs Through Opposite Helical Transduction Motions

    PubMed Central

    Wang, Boyuan; Zhao, Aishan; Novick, Richard; Muir, Tom W.

    2014-01-01

    Summary Staphylococcus aureus virulence is regulated when secreted autoinducing peptides (AIPs) are recognized by a membrane-bound receptor histidine kinase (RHK), AgrC. Some AIPs are agonists of virulence gene expression, while others are antagonists. It is unclear how AIP binding regulates AgrC activity. Here, we reconstitute an AgrC family member, AgrC-I, using nanometer-scale lipid bilayer discs. We show that AgrC-I requires membranes rich in anionic lipids to function. The agonist, AIP-I, binds AgrC-I non-cooperatively in a 2:2 stoichiometry, while an antagonist ligand, AIP-II, functions as an inverse agonist of the kinase activity. We also demonstrate the kinase and sensor domains in AgrC are connected by a helical linker whose conformational state exercises rheostat-like control over the kinase activity. Binding of agonist or inverse-agonist peptides results in twisting of the linker in different directions. These two observations provide a view of the molecular motions triggered by ligand binding in an intact membrane-bound RHK. PMID:24656130

  12. Activation and Desensitization of Peripheral Muscle and Neuronal Nicotinic Acetylcholine Receptors by Selected, Naturally-Occurring Pyridine Alkaloids.

    PubMed

    Green, Benedict T; Lee, Stephen T; Welch, Kevin D; Cook, Daniel; Kem, William R

    2016-01-01

    Teratogenic alkaloids can cause developmental defects due to the inhibition of fetal movement that results from desensitization of fetal muscle-type nicotinic acetylcholine receptors (nAChRs). We investigated the ability of two known teratogens, the piperidinyl-pyridine anabasine and its 1,2-dehydropiperidinyl analog anabaseine, to activate and desensitize peripheral nAChRs expressed in TE-671 and SH-SY5Y cells. Activation-concentration response curves for each alkaloid were obtained in the same multi-well plate. To measure rapid desensitization, cells were first exposed to five potentially-desensitizing concentrations of each alkaloid in log10 molar increments from 10 nM to 100 µM and then to a fixed concentration of acetylcholine (ACh), which alone produces near-maximal activation. The fifty percent desensitization concentration (DC50) was calculated from the alkaloid concentration-ACh response curve. Agonist fast desensitization potency was predicted by the agonist potency measured in the initial response. Anabaseine was a more potent desensitizer than anabasine. Relative to anabaseine, nicotine was more potent to autonomic nAChRs, but less potent to the fetal neuromuscular nAChRs. Our experiments have demonstrated that anabaseine is more effective at desensitizing fetal muscle-type nAChRs than anabasine or nicotine and, thus, it is predicted to be more teratogenic. PMID:27384586

  13. Non-Nutrient, Naturally Occurring Phenolic Compounds with Antioxidant Activity for the Prevention and Treatment of Periodontal Diseases.

    PubMed

    Varela-López, Alfonso; Bullón, Pedro; Giampieri, Francesca; Quiles, José L

    2015-01-01

    One of the main factors able to explain the pathophysiological mechanism of inflammatory conditions that occur in periodontal disease is oxidative stress. Given the emerging understanding of this relationship, host-modulatory therapies using antioxidants could be interesting to prevent or slow the breakdown of soft and hard periodontal tissues. In this context, non-nutrient phenolic compounds of various foods and plants have received considerable attention in the last decade. Here, studies focusing on the relationship between different compounds of this type with periodontal disease have been collected. Among them, thymoquinone, coenzyme Q (CoQ), mangiferin, resveratrol, verbascoside and some flavonoids have shown to prevent or ameliorate periodontal tissues damage in animal models. However evidence regarding this effect in humans is poor and only limited to topical treatments with CoQ and catechins. Along with animal experiments, in vitro studies indicate that possible mechanisms by which these compounds might exert their protective effects include antioxidative properties, oxygen and nitrogen scavenging abilities, and also inhibitory effects on cell signaling cascades related to inflammatory processes which have an effect on RNS or ROS production as well as on antioxidant defense systems. PMID:26783837

  14. Non-Nutrient, Naturally Occurring Phenolic Compounds with Antioxidant Activity for the Prevention and Treatment of Periodontal Diseases

    PubMed Central

    Varela-López, Alfonso; Bullón, Pedro; Giampieri, Francesca; Quiles, José L.

    2015-01-01

    One of the main factors able to explain the pathophysiological mechanism of inflammatory conditions that occur in periodontal disease is oxidative stress. Given the emerging understanding of this relationship, host-modulatory therapies using antioxidants could be interesting to prevent or slow the breakdown of soft and hard periodontal tissues. In this context, non-nutrient phenolic compounds of various foods and plants have received considerable attention in the last decade. Here, studies focusing on the relationship between different compounds of this type with periodontal disease have been collected. Among them, thymoquinone, coenzyme Q (CoQ), mangiferin, resveratrol, verbascoside and some flavonoids have shown to prevent or ameliorate periodontal tissues damage in animal models. However evidence regarding this effect in humans is poor and only limited to topical treatments with CoQ and catechins. Along with animal experiments, in vitro studies indicate that possible mechanisms by which these compounds might exert their protective effects include antioxidative properties, oxygen and nitrogen scavenging abilities, and also inhibitory effects on cell signaling cascades related to inflammatory processes which have an effect on RNS or ROS production as well as on antioxidant defense systems. PMID:26783837

  15. Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR

    PubMed Central

    Pondugula, Satyanarayana R.; Flannery, Patrick C.; Abbott, Kodye L.; Coleman, Elaine S.; Mani, Sridhar; Samuel, Temesgen; Xie, Wen

    2015-01-01

    Activation of human pregnane X receptor (hPXR)-regulated expression of cytochrome P450 3A4 (CYP3A4) and multidrug resistance protein 1 (MDR1) plays an important role in mediating adverse drug interactions. Given the common use of natural products as part of adjunct human health behavior, there is a growing concern about natural products for their potential to induce undesired drug interactions through the activation of hPXR-regulated CYP3A4 and MDR1. Here, we studied whether 3,3′-diindolylmethane (DIM), a natural health supplement, could induce hPXR-mediated regulation of CYP3A4 and MDR1 in human hepatocytes and intestinal cells. DIM, at its physiologically relevant concentrations, not only induced hPXR transactivation of CYP3A4 promoter activity but also induced gene expression of CYP3A4 and MDR1. DIM decreased intracellular accumulation of MDR1 substrate rhodamine 123, suggesting that DIM induces the functional expression of MDR1. Pharmacologic inhibition or genetic knockdown of hPXR resulted in attenuation of DIM induced CYP3A4 and MDR1 gene expression, suggesting that DIM induces CYP3A4 and MDR1 in an hPXR-dependent manner. Together, these results support our conclusion that DIM induces hPXR-regulated CYP3A4 and MDR1 gene expression. The inductive effects of DIM on CYP3A4 and MDR1 expression caution the use of DIM in conjunction with other medications metabolized and transported via CYP3A4 and MDR1, respectively. PMID:25542144

  16. Where does brain neural activation in aesthetic responses to visual art occur? Meta-analytic evidence from neuroimaging studies.

    PubMed

    Boccia, M; Barbetti, S; Piccardi, L; Guariglia, C; Ferlazzo, F; Giannini, A M; Zaidel, D W

    2016-01-01

    Here we aimed at finding the neural correlates of the general aspect of visual aesthetic experience (VAE) and those more strictly correlated with the content of the artworks. We applied a general activation likelihood estimation (ALE) meta-analysis to 47 fMRI experiments described in 14 published studies. We also performed four separate ALE analyses in order to identify the neural substrates of reactions to specific categories of artworks, namely portraits, representation of real-world-visual-scenes, abstract paintings, and body sculptures. The general ALE revealed that VAE relies on a bilateral network of areas, and the individual ALE analyses revealed different maximal activation for the artworks' categories as function of their content. Specifically, different content-dependent areas of the ventral visual stream are involved in VAE, but a few additional brain areas are involved as well. Thus, aesthetic-related neural responses to art recruit widely distributed networks in both hemispheres including content-dependent brain areas of the ventral visual stream. Together, the results suggest that aesthetic responses are not independent of sensory, perceptual, and cognitive processes.

  17. Where does brain neural activation in aesthetic responses to visual art occur? Meta-analytic evidence from neuroimaging studies.

    PubMed

    Boccia, M; Barbetti, S; Piccardi, L; Guariglia, C; Ferlazzo, F; Giannini, A M; Zaidel, D W

    2016-01-01

    Here we aimed at finding the neural correlates of the general aspect of visual aesthetic experience (VAE) and those more strictly correlated with the content of the artworks. We applied a general activation likelihood estimation (ALE) meta-analysis to 47 fMRI experiments described in 14 published studies. We also performed four separate ALE analyses in order to identify the neural substrates of reactions to specific categories of artworks, namely portraits, representation of real-world-visual-scenes, abstract paintings, and body sculptures. The general ALE revealed that VAE relies on a bilateral network of areas, and the individual ALE analyses revealed different maximal activation for the artworks' categories as function of their content. Specifically, different content-dependent areas of the ventral visual stream are involved in VAE, but a few additional brain areas are involved as well. Thus, aesthetic-related neural responses to art recruit widely distributed networks in both hemispheres including content-dependent brain areas of the ventral visual stream. Together, the results suggest that aesthetic responses are not independent of sensory, perceptual, and cognitive processes. PMID:26619805

  18. Subchronic oral toxicity and cardiovascular safety pharmacology studies of resveratrol, a naturally occurring polyphenol with cancer preventive activity

    PubMed Central

    Johnson, W.D.; Morrissey, R.L.; Usborne, A.L.; Kapetanovic, I.; Crowell, J.A.; Muzzio, M.; McCormick, D.L.

    2011-01-01

    To characterize the subchronic oral toxicity of resveratrol, CD rats received daily gavage doses of 0, 200, 400, or 1000 mg resveratrol/kg/day, and beagle dogs received daily capsule doses of 0, 200, 600, or 1200 mg resveratrol/kg/day for 90 days. Resveratrol induced only minimal toxicity, consisting of dose-related reductions in body weight gain in female rats and both sexes of dogs, and a statistically significant increase in bilirubin levels in rats at the 1000 mg/kg/day dose. Clinical observations, hematology, ophthalmology, neurotoxicity evaluations (functional observational batteries), organ weights, and gross pathology provided no biologically significant evidence of resveratrol toxicity in either species. In rats, the high dose of resveratrol reduced the incidence of cardiomyopathy; no other microscopic changes were seen. Histopathologic changes in dogs were limited to minimal inflammatory infiltrates in the kidney and urinary bladder, which were not considered toxicologically significant. A cardiovascular safety pharmacology (telemetry) study in dogs revealed no evidence of resveratrol toxicity. Based on body weight effects, the No Observed Adverse Effect Level (NOAEL) for resveratrol was 200 mg/kg/day in rats and 600 mg/kg/day in dogs. The apparent cardioprotective activity of resveratrol in rats demonstrates that its potentially beneficial activities may extend beyond efficacy in cancer prevention. PMID:21939727

  19. Social Motility of African Trypanosomes Is a Property of a Distinct Life-Cycle Stage That Occurs Early in Tsetse Fly Transmission

    PubMed Central

    Imhof, Simon; Knüsel, Sebastian; Gunasekera, Kapila; Vu, Xuan Lan; Roditi, Isabel

    2014-01-01

    The protozoan pathogen Trypanosoma brucei is transmitted between mammals by tsetse flies. The first compartment colonised by trypanosomes after a blood meal is the fly midgut lumen. Trypanosomes present in the lumen—designated as early procyclic forms—express the stage-specific surface glycoproteins EP and GPEET procyclin. When the trypanosomes establish a mature infection and colonise the ectoperitrophic space, GPEET is down-regulated, and EP becomes the major surface protein of late procyclic forms. A few years ago, it was discovered that procyclic form trypanosomes exhibit social motility (SoMo) when inoculated on a semi-solid surface. We demonstrate that SoMo is a feature of early procyclic forms, and that late procyclic forms are invariably SoMo-negative. In addition, we show that, apart from GPEET, other markers are differentially expressed in these two life-cycle stages, both in culture and in tsetse flies, indicating that they have different biological properties and should be considered distinct stages of the life cycle. Differentially expressed genes include two closely related adenylate cyclases, both hexokinases and calflagins. These findings link the phenomenon of SoMo in vitro to the parasite forms found during the first 4–7 days of a midgut infection. We postulate that ordered group movement on plates reflects the migration of parasites from the midgut lumen into the ectoperitrophic space within the tsetse fly. Moreover, the process can be uncoupled from colonisation of the salivary glands. Although they are the major surface proteins of procyclic forms, EP and GPEET are not essential for SoMo, nor, as shown previously, are they required for near normal colonisation of the fly midgut. PMID:25357194

  20. Social motility of African trypanosomes is a property of a distinct life-cycle stage that occurs early in tsetse fly transmission.

    PubMed

    Imhof, Simon; Knüsel, Sebastian; Gunasekera, Kapila; Vu, Xuan Lan; Roditi, Isabel

    2014-10-01

    The protozoan pathogen Trypanosoma brucei is transmitted between mammals by tsetse flies. The first compartment colonised by trypanosomes after a blood meal is the fly midgut lumen. Trypanosomes present in the lumen-designated as early procyclic forms-express the stage-specific surface glycoproteins EP and GPEET procyclin. When the trypanosomes establish a mature infection and colonise the ectoperitrophic space, GPEET is down-regulated, and EP becomes the major surface protein of late procyclic forms. A few years ago, it was discovered that procyclic form trypanosomes exhibit social motility (SoMo) when inoculated on a semi-solid surface. We demonstrate that SoMo is a feature of early procyclic forms, and that late procyclic forms are invariably SoMo-negative. In addition, we show that, apart from GPEET, other markers are differentially expressed in these two life-cycle stages, both in culture and in tsetse flies, indicating that they have different biological properties and should be considered distinct stages of the life cycle. Differentially expressed genes include two closely related adenylate cyclases, both hexokinases and calflagins. These findings link the phenomenon of SoMo in vitro to the parasite forms found during the first 4-7 days of a midgut infection. We postulate that ordered group movement on plates reflects the migration of parasites from the midgut lumen into the ectoperitrophic space within the tsetse fly. Moreover, the process can be uncoupled from colonisation of the salivary glands. Although they are the major surface proteins of procyclic forms, EP and GPEET are not essential for SoMo, nor, as shown previously, are they required for near normal colonisation of the fly midgut.

  1. Early ERK1/2 activation promotes DRP1-dependent mitochondrial fission necessary for cell reprogramming.

    PubMed

    Prieto, Javier; León, Marian; Ponsoda, Xavier; Sendra, Ramón; Bort, Roque; Ferrer-Lorente, Raquel; Raya, Angel; López-García, Carlos; Torres, Josema

    2016-01-01

    During the process of reprogramming to induced pluripotent stem (iPS) cells, somatic cells switch from oxidative to glycolytic metabolism, a transition associated with profound mitochondrial reorganization. Neither the importance of mitochondrial remodelling for cell reprogramming, nor the molecular mechanisms controlling this process are well understood. Here, we show that an early wave of mitochondrial fragmentation occurs upon expression of reprogramming factors. Reprogramming-induced mitochondrial fission is associated with a minor decrease in mitochondrial mass but not with mitophagy. The pro-fission factor Drp1 is phosphorylated early in reprogramming, and its knockdown and inhibition impairs both mitochondrial fragmentation and generation of iPS cell colonies. Drp1 phosphorylation depends on Erk activation in early reprogramming, which occurs, at least in part, due to downregulation of the MAP kinase phosphatase Dusp6. Taken together, our data indicate that mitochondrial fission controlled by an Erk-Drp1 axis constitutes an early and necessary step in the reprogramming process to pluripotency. PMID:27030341

  2. Early ERK1/2 activation promotes DRP1-dependent mitochondrial fission necessary for cell reprogramming

    PubMed Central

    Prieto, Javier; León, Marian; Ponsoda, Xavier; Sendra, Ramón; Bort, Roque; Ferrer-Lorente, Raquel; Raya, Angel; López-García, Carlos; Torres, Josema

    2016-01-01

    During the process of reprogramming to induced pluripotent stem (iPS) cells, somatic cells switch from oxidative to glycolytic metabolism, a transition associated with profound mitochondrial reorganization. Neither the importance of mitochondrial remodelling for cell reprogramming, nor the molecular mechanisms controlling this process are well understood. Here, we show that an early wave of mitochondrial fragmentation occurs upon expression of reprogramming factors. Reprogramming-induced mitochondrial fission is associated with a minor decrease in mitochondrial mass but not with mitophagy. The pro-fission factor Drp1 is phosphorylated early in reprogramming, and its knockdown and inhibition impairs both mitochondrial fragmentation and generation of iPS cell colonies. Drp1 phosphorylation depends on Erk activation in early reprogramming, which occurs, at least in part, due to downregulation of the MAP kinase phosphatase Dusp6. Taken together, our data indicate that mitochondrial fission controlled by an Erk-Drp1 axis constitutes an early and necessary step in the reprogramming process to pluripotency. PMID:27030341

  3. [Catalogues of therapeutic nursing activities in neurological early rehabilitation].

    PubMed

    Lautenschläger, S; Wallesch, C W

    2015-02-01

    Under the German DRG-system, hospital-based rehabilitation of still critically ill patients becomes increasingly important. The code for early neurological rehabilitation in the DRG-system's (Diagnosis Related Groups) list of operations and procedures requires an average daily therapeutic intensity of 300 min, part of which is being contributed by therapeutic nursing. As therapeutic aspects are integrated in other nursing activities, it is difficult to separate its time consumption. This problem is pragmatically resolved by catalogues of therapeutic nursing activities which assign plausible amounts of therapeutic minutes to each activity. The 4 catalogues that are used most often are described and compared. Nursing science has not focused yet on therapeutic nursing. PMID:25317957

  4. An Evaluation of Computer Based Activities in an Early Intervention Program. A Report to the Early Special Education Program.

    ERIC Educational Resources Information Center

    Elliott, Alison; Hall, Neil

    This study investigated ways of using computer-based learning activities to complement curriculum practices in preschool programs with an early intervention component through the use of computer-based learning activities. Particular attention was given to supporting the development of young children's early mathematical skills. The study took…

  5. Selective phthalate activation of naturally occurring human constitutive androstane receptor splice variants and the pregnane X receptor.

    PubMed

    DeKeyser, Joshua G; Laurenzana, Elizabeth M; Peterson, Eric C; Chen, Tao; Omiecinski, Curtis J

    2011-04-01

    Phthalates and other endocrine-disruptive chemicals are manufactured in large quantities for use as plasticizers and other commercial applications, resulting in ubiquitous human exposure and thus, concern regarding their toxicity. Innate defense against small molecule exposures is controlled in large part by the constitutive androstane receptor (CAR) and the pregnane X receptor (PXR). The human CAR gene undergoes multiple alternative splicing events resulting in the CAR2 and CAR3 variant receptors. Recent studies from our laboratory show that CAR2 is potently and specifically activated by di(2-ethylhexyl) phthalate (DEHP). We hypothesized that alternative splicing is a mechanism for increasing CAR's functional diversity, broadening the human receptors' repertoire of response to environmental xenobiotics. In these studies, we examine the interaction of alternatively spliced CARs and PXR with a range of suspected endocrine disruptors, including phthalates, bisphenol A (BPA), and 4-N-nonylphenol (NP). Transactivation and two-hybrid studies in COS-1 cells revealed differential selectivity of endocrine-disrupting chemicals for the variant CAR and PXR. Ex vivo studies showed DEHP and di-isononyl phthalate potently induced CYP2B6 and CYP3A4 expression in human hepatocytes. Mutation analysis of CAR2, in silico modeling, and ligand docking studies suggested that the SPTV amino acid insertion of CAR2 creates a unique ligand-binding pocket. Alternative gene splicing results in variant CAR receptors that selectively recognize phthalates and BPA. The interaction of phthalates with CAR and PXR suggests a xenobiotic response that is complex and biologically redundant.

  6. SECONDARY WASTE MANAGEMENT STRATEGY FOR EARLY LOW ACTIVITY WASTE TREATMENT

    SciTech Connect

    TW, CRAWFORD

    2008-07-17

    This study evaluates parameters relevant to River Protection Project secondary waste streams generated during Early Low Activity Waste operations and recommends a strategy for secondary waste management that considers groundwater impact, cost, and programmatic risk. The recommended strategy for managing River Protection Project secondary waste is focused on improvements in the Effiuent Treatment Facility. Baseline plans to build a Solidification Treatment Unit adjacent to Effluent Treatment Facility should be enhanced to improve solid waste performance and mitigate corrosion of tanks and piping supporting the Effiuent Treatment Facility evaporator. This approach provides a life-cycle benefit to solid waste performance and reduction of groundwater contaminants.

  7. Neuropathic pain: Early spontaneous afferent activity is the trigger

    PubMed Central

    Xie, Wenrui; Strong, Judith A.; Meij, Johanna T.A.; Zhang, Jun-Ming; Yu, Lei

    2005-01-01

    Intractable neuropathic pain often results from nerve injury. One immediate event in damaged nerve is a sustained increase in spontaneous afferent activity, which has a well-established role in ongoing pain. Using two rat models of neuropathic pain, the CCI and SNI models, we show that local, temporary nerve blockade of this afferent activity permanently inhibits the subsequent development of both thermal hyperalgesia and mechanical allodynia. Timing is critical—the nerve blockade must last at least 3–5 days and is effective if started immediately after nerve injury, but not if started at 10 days after injury when neuropathic pain is already established. Effective nerve blockade also prevents subsequent development of spontaneous afferent activity measured electrophysiologically. Similar results were obtained in both pain models, and with two blockade methods (200 mg of a depot form bupivacaine at the injury site, or perfusion of the injured nerve just proximal to the injury site with TTX). These results indicate that early spontaneous afferent fiber activity is the key trigger for the development of pain behaviors, and suggest that spontaneous activity may be required for many of the later changes in the sensory neurons, spinal cord, and brain observed in neuropathic pain models. Many pre-clinical and clinical studies of pre-emptive analgesia have used much shorter duration of blockade, or have not started immediately after the injury. Our results suggest that effective pre-emptive analgesia can be achieved only when nerve block is administered early after injury and lasts several days. PMID:15964687

  8. Change in Vitamin D Levels Occurs Early after Antiretroviral Therapy Initiation and Depends on Treatment Regimen in Resource-Limited Settings

    PubMed Central

    Havers, Fiona P.; Detrick, Barbara; Cardoso, Sandra W.; Berendes, Sima; Lama, Javier R.; Sugandhavesa, Patcharaphan; Mwelase, Noluthando H.; Campbell, Thomas B.; Gupta, Amita

    2014-01-01

    Study Background Vitamin D has wide-ranging effects on the immune system, and studies suggest that low serum vitamin D levels are associated with worse clinical outcomes in HIV. Recent studies have identified an interaction between antiretrovirals used to treat HIV and reduced serum vitamin D levels, but these studies have been done in North American and European populations. Methods Using a prospective cohort study design nested in a multinational clinical trial, we examined the effect of three combination antiretroviral (cART) regimens on serum vitamin D levels in 270 cART-naïve, HIV-infected adults in nine diverse countries, (Brazil, Haiti, Peru, Thailand, India, Malawi, South Africa, Zimbabwe and the United States). We evaluated the change between baseline serum vitamin D levels and vitamin D levels 24 and 48 weeks after cART initiation. Results Serum vitamin D levels decreased significantly from baseline to 24 weeks among those randomized to efavirenz/lamivudine/zidovudine (mean change: −7.94 [95% Confidence Interval (CI) −10.42, −5.54] ng/ml) and efavirenz/emtricitabine/tenofovir-DF (mean change: −6.66 [95% CI −9.40, −3.92] ng/ml) when compared to those randomized to atazanavir/emtricitabine/didanosine-EC (mean change: −2.29 [95% CI –4.83, 0.25] ng/ml). Vitamin D levels did not change significantly between week 24 and 48. Other factors that significantly affected serum vitamin D change included country (p<0.001), season (p<0.001) and baseline vitamin D level (p<0.001). Conclusion Efavirenz-containing cART regimens adversely affected vitamin D levels in patients from economically, geographically and racially diverse resource-limited settings. This effect was most pronounced early after cART initiation. Research is needed to define the role of Vitamin D supplementation in HIV care. PMID:24752177

  9. Searching for a good model for systemic sclerosis: the molecular profile and vascular changes occurring in UCD-200 chickens strongly resemble the early phase of human systemic sclerosis

    PubMed Central

    Di Benedetto, Paola; Dietrich, Hermann; Ruscitti, Piero; Liakouli, Vasiliki; Carubbi, Francesco; Pantano, Ilenia; Berardicurti, Onorina; Sgonc, Roswitha; Giacomelli, Roberto

    2016-01-01

    Introduction Vascular injury and endothelial cell (EC) apoptosis are the earliest events in systemic sclerosis (SSc), before the onset of fibrosis, and stromal cell-derived factor 1 (SDF-1), vascular endothelial growth factor (VEGFA), endothelin-1 (ET-1) and platelet-derived growth factors (PDGF-BB) represent the key molecules to study the link between vascular injury and fibrosis during SSc. The University of California at Davis line 200 (UCD-200) chickens display the same hallmarks of human SSc: vascular occlusion, perivascular lymphocytic infiltration and fibrosis of skin and internal organs. In this study we assessed both cytokines and growth factors involved in the early phases of the UCD-200 chickens’ skin lesions, to determine whether these animals might represent an appropriate experimental model to study the pathogenesis of SSc. Material and methods Immunofluorescence analysis was performed on human SSc skin, human healthy control (hHC) skin, UCD-200 combs and HC H.B15 chicken (cHC) combs, using anti-SDF-1, CXCR4, VEGFA, VEGF receptor 1 (VEGFR1), VEGF receptor 2 (VEGFR2), ET-1, ET receptor A (ETAR), ET receptor B (ETBR), PDGF-BB, and PDGF receptor (PDGFR) antibodies. The plasma concentrations of SDF-1, VEGFA, ET-1 and PDGF-BB were determined by ELISA. Results All the molecules analyzed showed higher levels in SSc patients and UCD-200 chickens than in hHC and cHC. Furthermore, the levels of the assessed molecules paralleled the severity of comb involvement. Conclusions The molecular similarities between avian and human SSc, observed in this study, suggest that the UCD-200 chickens are an interesting model for translational approaches to SSc. PMID:27478465

  10. Early activation of microglia and astrocytes in mouse models of spinocerebellar ataxia type 1.

    PubMed

    Cvetanovic, M; Ingram, M; Orr, H; Opal, P

    2015-03-19

    Spinocerebellar ataxia type 1 (SCA1) is an incurable, dominantly inherited neurodegenerative disease of the cerebellum caused by a polyglutamine-repeat expansion in the protein ataxin-1 (ATXN1). While analysis of human autopsy material indicates significant glial pathology in SCA1, previous research has focused on characterizing neuronal dysfunction. In this study, we characterized astrocytic and microglial response in SCA1 using a comprehensive array of mouse models. We have discovered that astrocytes and microglia are activated very early in SCA1 pathogenesis even when mutant ATXN1 expression was limited to Purkinje neurons. Glial activation occurred in the absence of neuronal death, suggesting that glial activation results from signals emanating from dysfunctional neurons. Finally, in all different models examined glial activation closely correlated with disease progression, supporting the development of glial-based biomarkers to follow disease progression.

  11. Development of the mouse dermal adipose layer occurs independently of subcutaneous adipose tissue and is marked by restricted early expression of FABP4.

    PubMed

    Wojciechowicz, Kamila; Gledhill, Karl; Ambler, Carrie A; Manning, Craig B; Jahoda, Colin A B

    2013-01-01

    The laboratory mouse is a key animal model for studies of adipose biology, metabolism and disease, yet the developmental changes that occur in tissues and cells that become the adipose layer in mouse skin have received little attention. Moreover, the terminology around this adipose body is often confusing, as frequently no distinction is made between adipose tissue within the skin, and so called subcutaneous fat. Here adipocyte development in mouse dorsal skin was investigated from before birth to the end of the first hair follicle growth cycle. Using Oil Red O staining, immunohistochemistry, quantitative RT-PCR and TUNEL staining we confirmed previous observations of a close spatio-temporal link between hair follicle development and the process of adipogenesis. However, unlike previous studies, we observed that the skin adipose layer was created from cells within the lower dermis. By day 16 of embryonic development (e16) the lower dermis was demarcated from the upper dermal layer, and commitment to adipogenesis in the lower dermis was signalled by expression of FABP4, a marker of adipocyte differentiation. In mature mice the skin adipose layer is separated from underlying subcutaneous adipose tissue by the panniculus carnosus. We observed that the skin adipose tissue did not combine or intermix with subcutaneous adipose tissue at any developmental time point. By transplanting skin isolated from e14.5 mice (prior to the start of adipogenesis), under the kidney capsule of adult mice, we showed that skin adipose tissue develops independently and without influence from subcutaneous depots. This study has reinforced the developmental link between hair follicles and skin adipocyte biology. We argue that because skin adipocytes develop from cells within the dermis and independently from subcutaneous adipose tissue, that it is accurately termed dermal adipose tissue and that, in laboratory mice at least, it represents a separate adipose depot.

  12. Factors Associated with Early Platelet Activation in Obese Children

    PubMed Central

    García, Anel Gómez; Núñez, Guillermina García; Sandoval, Martha Eva Viveros; Castellanos, Sergio Gutierrez; Aguilar, Cleto Alvarez

    2014-01-01

    Objective To investigate the factors associated with platelet activation in obese children. Design Cross-sectional study. Setting Department of Pediatrics of Regional Hospital N∘ 1 of Mexican Institute of Social Security in Morelia, Michoacán, Mexico. Participants 79 obese and 64 non-obese children between the ages of 5 and 10 years. Main Outcomes Measures Obese children (body mass index [BMI] >85 in growth curves for Centers for Disease Control/National Center for Health Statistics), and the control group of 64 non-obese children (percentile <85), % body fat, platelet activation was assessed by sP-selectin. Other measures were leptin, uric acid (UA), von Willebrand Factor (vWF), plasminogen activator inhibitor (PAI-1), lipid profile, and glucose. Results Obese children displayed higher plasma sP-selectin, leptin, PAI-1, and vWF than non-obese children. In the univariate logistic regression analysis, leptin, vWF, UA, and high density lipoprotein (HDL), but not with PAI-1, were factors associated with platelet activation. By stepwise linear regression analysis adjusted by sex and age, the best predictor variables for platelet activation were leptin (β:0.381; t:4.665; P=0.0001), vWF (β:0.211; t:2.926; P=0.004), UA (β:0.166; t:2.146; P=0.034), and HDL (β:−0.215; t:−2.819; P=0.006). Conclusions Obese children have a higher risk of developing early platelet activation. Factors associated with platelet activation were Leptin, vWF, UA, and HDL. Further studies involving larger numbers of patients over a longer duration are needed to understand the possible molecular mechanism underlying the association between leptin, vWF, and UA and endothelial activation and/or endothelial damage/dysfunction in obese children and its influence in cardiovascular disease in adults. PMID:24415745

  13. Tracking of physical activity and fitness during the early years.

    PubMed

    Caldwell, Hilary A T; Proudfoot, Nicole A; King-Dowling, Sara; Di Cristofaro, Natascja A; Cairney, John; Timmons, Brian W

    2016-05-01

    The early years are characterized by rapid physical growth and the development of behaviours such as physical activity. The objectives of this study were to assess the 12-month changes in and the tracking of physical activity and fitness in 400 preschoolers (201 boys, 4.5 ± 0.9 years of age). Physical activity data, expressed as minutes per day and as the percentage of time spent at various intensities while wearing an accelerometer, were collected in 3-s epochs for 7 days. Short-term muscle power, assessed with a 10-s modified Wingate Anaerobic Test, was expressed as absolute (W) and relative (W/kg) peak power (PP) and mean power (MP). Aerobic fitness, assessed with the Bruce Protocol progressive treadmill test, was expressed as maximal treadmill time and heart rate recovery (HRR). Light physical activity decreased by 3.2 min/day (p < 0.05), whereas vigorous physical activity increased by 3.7 min/day (p < 0.001), from year 1 to year 2. Physical activity exhibited moderate tracking on the basis of Spearman correlations (r = 0.45-0.59, p < 0.001) and fair tracking on the basis of κ statistics (κ = 0.26-0.38). PP and MP increased from year 1 (PP, 94.1 ± 37.3 W; MP, 84.1 ± 30.9 W) to year 2 (PP, 125.6 ± 36.2 W; MP, 112.3 ± 32.2 W) (p < 0.001) and tracked moderately to substantially (PP, r = 0.89, κ = 0.61; MP, r = 0.86, κ = 0.56). Time to exhaustion on the treadmill increased from 9.4 ± 2.3 min to 11.8 ± 2.3 min (p < 0.001) and tracked strongly (r = 0.82, κ = 0.56). HRR was unchanged at 65 ± 14 beats/min (p = 0.297) and tracked fairly (r = 0.52, κ = 0.23). The findings indicate that fitness tracks better than physical activity over a 12-month period during the early years. PMID:27045869

  14. Early life stress affects limited regional brain activity in depression.

    PubMed

    Du, Lian; Wang, Jingjie; Meng, Ben; Yong, Na; Yang, Xiangying; Huang, Qingling; Zhang, Yan; Yang, Lingling; Qu, Yuan; Chen, Zhu; Li, Yongmei; Lv, Fajin; Hu, Hua

    2016-05-03

    Early life stress (ELS) can alter brain function and increases the risk of major depressive disorder (MDD) in later life. This study investigated whether ELS contributes to differences in regional brain activity between MDD patients and healthy controls (HC), as measured by amplitude of low-frequency fluctuation (ALFF)/fractional (f)ALFF. Eighteen first-episode, treatment-naïve MDD patients and HC were assessed with the Childhood Trauma Questionnaire and resting-state functional magnetic resonance imaging. We compared ALFF/fALFF between MDD patients and HC, with or without controlling for ELS, and determined whether ELS level was correlated with regional brain activity in each group. After regressing out ELS, we found that ALFF increased in bilateral amygdala and left orbital/cerebellum, while fALFF decreased in left inferior temporal and right middle frontal gyri in MDD patients relative to controls. ELS positively correlated with regional activity in the left cerebellum in MDD and in the right post-central/inferior temporal/superior frontal cingulate, inferior frontal gyrus and bilateral cerebellum in HC. Our findings indicate that there is only very limited region showing correlation between ELS and brain activity in MDD, while diverse areas in HC, suggesting ELS has few impacts on MDD patients.

  15. Early life stress affects limited regional brain activity in depression

    PubMed Central

    Du, Lian; Wang, Jingjie; Meng, Ben; Yong, Na; Yang, Xiangying; Huang, Qingling; Zhang, Yan; Yang, Lingling; Qu, Yuan; Chen, Zhu; Li, Yongmei; Lv, Fajin; Hu, Hua

    2016-01-01

    Early life stress (ELS) can alter brain function and increases the risk of major depressive disorder (MDD) in later life. This study investigated whether ELS contributes to differences in regional brain activity between MDD patients and healthy controls (HC), as measured by amplitude of low-frequency fluctuation (ALFF)/fractional (f)ALFF. Eighteen first-episode, treatment-naïve MDD patients and HC were assessed with the Childhood Trauma Questionnaire and resting-state functional magnetic resonance imaging. We compared ALFF/fALFF between MDD patients and HC, with or without controlling for ELS, and determined whether ELS level was correlated with regional brain activity in each group. After regressing out ELS, we found that ALFF increased in bilateral amygdala and left orbital/cerebellum, while fALFF decreased in left inferior temporal and right middle frontal gyri in MDD patients relative to controls. ELS positively correlated with regional activity in the left cerebellum in MDD and in the right post-central/inferior temporal/superior frontal cingulate, inferior frontal gyrus and bilateral cerebellum in HC. Our findings indicate that there is only very limited region showing correlation between ELS and brain activity in MDD, while diverse areas in HC, suggesting ELS has few impacts on MDD patients. PMID:27138376

  16. Complement activation and choriocapillaris loss in early AMD: implications for pathophysiology and therapy.

    PubMed

    Whitmore, S Scott; Sohn, Elliott H; Chirco, Kathleen R; Drack, Arlene V; Stone, Edwin M; Tucker, Budd A; Mullins, Robert F

    2015-03-01

    Age-related macular degeneration (AMD) is a common and devastating disease that can result in severe visual dysfunction. Over the last decade, great progress has been made in identifying genetic variants that contribute to AMD, many of which lie in genes involved in the complement cascade. In this review we discuss the significance of complement activation in AMD, particularly with respect to the formation of the membrane attack complex in the aging choriocapillaris. We review the clinical, histological and biochemical data that indicate that vascular loss in the choroid occurs very early in the pathogenesis of AMD, and discuss the potential impact of vascular dropout on the retinal pigment epithelium, Bruch's membrane and the photoreceptor cells. Finally, we present a hypothesis for the pathogenesis of early AMD and consider the implications of this model on the development of new therapies.

  17. Complement activation and choriocapillaris loss in early AMD: Implications for pathophysiology and therapy

    PubMed Central

    Whitmore, S.Scott; Sohn, Elliott H.; Chirco, Kathleen R.; Drack, Arlene V.; Stone, Edwin M.; Tucker, Budd A.; Mullins, Robert F.

    2015-01-01

    Age-related macular degeneration (AMD) is a common and devastating disease that can result in severe visual dysfunction. Over the last decade, great progress has been made in identifying genetic variants that contribute to AMD, many of which lie in genes involved in the complement cascade. In this review we discuss the significance of complement activation in AMD, particularly with respect to the formation of the membrane attack complex in the aging choriocapillaris. We review the clinical, histological and biochemical data that indicate that vascular loss in the choroid occurs very early in the pathogenesis of AMD, and discuss the potential impact of vascular dropout on the retinal pigment epithelium, Bruch's membrane and the photoreceptor cells. Finally, we present a hypothesis for the pathogenesis of early AMD and consider the implications of this model on the development of new therapies. PMID:25486088

  18. Naturally occurring insecticides.

    PubMed Central

    Soloway, S B

    1976-01-01

    Naturally occurring insecticides are abundant and varied in their effects, though but a few are articles of commerce. Even for these, pyrethrum, nicotine, rotenone, hellebore, ryania, and sabadilla, there is a paucity of information on mammalian toxicology and environmental effects. In general, these materials are characterized favorably by low acute toxicity and ready dissipation in nature. Unfavorable aspects of natural insecticides are the contained mixture of active and inactive components and the low active ingredient content on a crop yield basis pointing to a high unit cost. Natural insecticides can serve additionally as leads to unnatural mimics, of which the commercially successful synthetic pyrethroids are prime examples. The chemical nature, relationship of insecticidal activity to chemical structure, occurrence, production, and utilization, registered uses, metabolism, and insect and mammalian toxicity are reviewed. PMID:789058

  19. Measurement of immediate-early gene activation- c-fos and beyond.

    PubMed

    Kovács, K J

    2008-06-01

    Immediate-early genes (IEG) are powerful tools for identifying activated neurosecretory neurones and extended circuits that affect neuroendocrine functions. The generally acknowledged scenario is when cells became activated, IEGs expressed and IEG-encoded transcription factors affect target gene expression. However, there are several examples in which: (i) neuronal activation occurs without induction of IEGs; (ii) IEG induction is not related to challenge-induced neuropeptide expression; and (iii) markers of neuronal activation are not expressed in chronically activated neurones. In spite of these limitations, the use of c-Fos and other regulatory- or effector transcription factors as markers of neuronal activation will continue to be an extremely powerful technique. Recently-developed models, including transgenic mice expressing different marker genes under the regulation of IEG promoters, will help to monitor neuronal activity in vivo or ex vivo and to reveal connection between activated neurones. Furthermore, combinations between novel imaging techniques, such as magnetic resonance and IEG-based mapping strategies, will open new means with which to study functional activity in the neurosecretory systems.

  20. Sympathetic activation and nitric oxide function in early hypertension

    PubMed Central

    Okamoto, Luis E.; Diedrich, André; Choi, Leena; Robertson, David; Farley, Ginnie; Paranjape, Sachin; Biaggioni, Italo

    2012-01-01

    The purpose of this study was to determine if tonic restrain of blood pressure by nitric oxide (NO) is impaired early in the development of hypertension. Impaired NO function is thought to contribute to hypertension, but it is not clear if this is explained by direct effects of NO on vascular tone or indirect modulation of sympathetic activity. We determined the blood pressure effect of NO synthase inhibition with Nω-monomethyl-l-arginine (l-NMMA) during autonomic blockade with trimethaphan to eliminate baroreflex buffering and NO modulation of autonomic tone. In this setting, impaired NO modulation of vascular tone would be reflected as a blunted pressor response to l-NMMA. We enrolled a total of 66 subjects (39 ± 1.3 yr old, 30 females), 20 normotensives, 20 prehypertensives (blood pressure between 120/80 and 140/90 mmHg), 17 hypertensives, and 9 smokers (included as “positive” controls of impaired NO function). Trimethaphan normalized blood pressure in hypertensives, suggesting increased sympathetic tone contributing to hypertension. In contrast, l-NMMA produced similar increases in systolic blood pressure in normal, prehypertensive, and hypertensive subjects (31 ± 2, 32 ± 2, and 30 ± 3 mmHg, respectively), whereas the response of smokers was blunted (16 ± 5 mmHg, P = 0.012). Our results suggest that sympathetic activity plays a role in hypertension. NO tonically restrains blood pressure by ∼30 mmHg, but we found no evidence of impaired modulation by NO of vascular tone contributing to the early development of hypertension. If NO deficiency contributes to hypertension, it is likely to be through its modulation of the autonomic nervous system, which was excluded in this study. PMID:22287587

  1. Gelsolin activity controls efficient early HIV-1 infection

    PubMed Central

    2013-01-01

    Background HIV-1 entry into target lymphocytes requires the activity of actin adaptors that stabilize and reorganize cortical F-actin, like moesin and filamin-A. These alterations are necessary for the redistribution of CD4-CXCR4/CCR5 to one pole of the cell, a process that increases the probability of HIV-1 Envelope (Env)-CD4/co-receptor interactions and that generates the tension at the plasma membrane necessary to potentiate fusion pore formation, thereby favouring early HIV-1 infection. However, it remains unclear whether the dynamic processing of F-actin and the amount of cortical actin available during the initial virus-cell contact are required to such events. Results Here we show that gelsolin restructures cortical F-actin during HIV-1 Env-gp120-mediated signalling, without affecting cell-surface expression of receptors or viral co-receptor signalling. Remarkably, efficient HIV-1 Env-mediated membrane fusion and infection of permissive lymphocytes were impaired when gelsolin was either overexpressed or silenced, which led to a loss or gain of cortical actin, respectively. Indeed, HIV-1 Env-gp120-induced F-actin reorganization and viral receptor capping were impaired under these experimental conditions. Moreover, gelsolin knockdown promoted HIV-1 Env-gp120-mediated aberrant pseudopodia formation. These perturbed-actin events are responsible for the inhibition of early HIV-1 infection. Conclusions For the first time we provide evidence that through its severing of cortical actin, and by controlling the amount of actin available for reorganization during HIV-1 Env-mediated viral fusion, entry and infection, gelsolin can constitute a barrier that restricts HIV-1 infection of CD4+ lymphocytes in a pre-fusion step. These findings provide important insights into the complex molecular and actin-associated dynamics events that underlie early viral infection. Thus, we propose that gelsolin is a new factor that can limit HIV-1 infection acting at a pre-fusion step

  2. Early social experience affects neural activity to affiliative facial gestures in newborn nonhuman primates

    PubMed Central

    Vanderwert, Ross E.; Simpson, Elizabeth A.; Paukner, Annika; Suomi, Stephen J.; Fox, Nathan A.; Ferrari, Pier F.

    2015-01-01

    A fundamental issue in cognitive neuroscience is how the brain encodes others’ actions and intentions. The discovery of an action-production-perception mechanism underpinning such a capacity advanced our knowledge of how these processes occur; however, no study has examined how the early postnatal environment may shape action-production-perception. Here we examined the effects of social experience on action-production-perception in 3-day-old rhesus macaques that were raised either with or without their biological mothers. We measured neonatal imitation skills and brain electrical activity responses while infants produced and observed facial gestures. We hypothesized that early social experiences may shape brain activity, as assessed via electroencephalogram suppression in the alpha band (5-7 Hz in infants, known as the mu rhythm) during action observation, and lead to more proficient imitation skills. Consistent with this hypothesis, infants reared by their mothers were more likely to imitate lipsmacking—a natural, affiliative gesture—and exhibited greater mu rhythm desynchronization while viewing lipsmacking gestures than nursery-reared infants. These effects were not found in response to tongue protrusion, a meaningless gesture, or a nonsocial control. These data suggest that socially enriched early experiences in the first days after birth increase brain sensitivity to socially relevant actions. PMID:26022835

  3. Effects of Online Self-Regulation Activitieson Physical Activity among Pregnant and Early Postpartum Women

    PubMed Central

    Niederdeppe, Jeff; Graham, Meredith; Olson, Christine; Gay, Geri

    2015-01-01

    Physical and psychological changes that occur during pregnancy present a unique challenge for women’s physical activity. Using a theory-based prospective design, this study examines effects of pregnant women’s (1) physical activity cognitions (self-efficacy, outcome expectancy, and safety beliefs) and (2) online self-regulation activities (goal-setting and self-monitoring) on subsequent changes in their physical activity intentions and behavior during pregnancy and immediately postpartum. We used data from three panel surveys administered to pregnant women enrolled in a web-based intervention to promote healthy pregnancy and postpartum weight, as well as log data on their use of self-regulatory features on the intervention website. Perceived self-efficacy and perceived safety of physical activity in pregnancy enhanced subsequent intentions to be physically active. Repeated goal-setting and monitoring of those goals helped to maintain positive intentions during pregnancy, but only repeated self-monitoring transferred positive intentions into actual behavior. Theoretically, this study offers a better understanding of the roles of self-regulation activities in the processes of goal-striving. We also discuss practical implications for encouraging physical activity among pregnant and early postpartum women. PMID:26132887

  4. Repositioning Early Childhood Leadership as Action and Activism

    ERIC Educational Resources Information Center

    Woodrow, Christine; Busch, Gillian

    2008-01-01

    Robust leadership is increasingly recognised as a critical element of healthy professions, yet some research suggests that early childhood practitioners do not readily identify with the concept of leadership. This article explores some dimensions of leadership in early childhood and how it is understood and practised in Australian early childhood…

  5. Increased error-related thalamic activity during early compared to late cocaine abstinence

    PubMed Central

    Li, Chiang-shan R.; Luo, Xi; Sinha, Rajita; Rounsaville, Bruce J.; Carroll, Kathleen M.; Malison, Robert T.; Ding, Yu-Shin; Zhang, Sheng; Ide, Jaime S.

    2010-01-01

    Altered cognitive control is implicated in the shaping of cocaine dependence. One of the key component processes of cognitive control is error monitoring. Our previous imaging work highlighted greater activity in distinct cortical and subcortical regions including the dorsal anterior cingulate cortex (dACC), thalamus and insula when participants committed an error during the stop signal task (Li et al., 2008b). Importantly, dACC, thalamic and insular activity has been associated with drug craving. One hypothesis is that the intense interoceptive activity during craving prevents these cerebral structures from adequately registering error and/or monitoring performance. Alternatively, the dACC, thalamus and insula show abnormally heightened responses to performance errors, suggesting that excessive responses to salient stimuli such as drug cues could precipitate craving. The two hypotheses would each predict decreased and increased activity during stop error (SE) as compared to stop success (SS) trials in the SST. Here we showed that cocaine dependent patients (PCD) experienced greater subjective feeling of loss of control and cocaine craving during early (average of day 6) compared to late (average of day 18) abstinence. Furthermore, compared to PCD during late abstinence, PCD scanned during early abstinence showed increased thalamic as well as insular but not dACC responses to errors (SE>SS). These findings support the hypothesis that heightened thalamic reactivity to salient stimuli co-occur with cocaine craving and loss of self control. PMID:20163923

  6. Early oxygen-utilization and brain activity in preterm infants.

    PubMed

    Tataranno, Maria Luisa; Alderliesten, Thomas; de Vries, Linda S; Groenendaal, Floris; Toet, Mona C; Lemmers, Petra M A; Vosse van de, Renè E; van Bel, Frank; Benders, Manon J N L

    2015-01-01

    The combined monitoring of oxygen supply and delivery using Near-InfraRed spectroscopy (NIRS) and cerebral activity using amplitude-integrated EEG (aEEG) could yield new insights into brain metabolism and detect potentially vulnerable conditions soon after birth. The relationship between NIRS and quantitative aEEG/EEG parameters has not yet been investigated. Our aim was to study the association between oxygen utilization during the first 6 h after birth and simultaneously continuously monitored brain activity measured by aEEG/EEG. Forty-four hemodynamically stable babies with a GA < 28 weeks, with good quality NIRS and aEEG/EEG data available and who did not receive morphine were included in the study. aEEG and NIRS monitoring started at NICU admission. The relation between regional cerebral oxygen saturation (rScO2) and cerebral fractional tissue oxygen extraction (cFTOE), and quantitative measurements of brain activity such as number of spontaneous activity transients (SAT) per minute (SAT rate), the interval in seconds (i.e. time) between SATs (ISI) and the minimum amplitude of the EEG in μV (min aEEG) were evaluated. rScO2 was negatively associated with SAT rate (β=-3.45 [CI=-5.76- -1.15], p=0.004) and positively associated with ISI (β=1.45 [CI=0.44-2.45], p=0.006). cFTOE was positively associated with SAT rate (β=0.034 [CI=0.009-0.059], p=0.008) and negatively associated with ISI (β=-0.015 [CI=-0.026- -0.004], p=0.007). Oxygen delivery and utilization, as indicated by rScO2 and cFTOE, are directly related to functional brain activity, expressed by SAT rate and ISI during the first hours after birth, showing an increase in oxygen extraction in preterm infants with increased early electro-cerebral activity. NIRS monitored oxygenation may be a useful biomarker of brain vulnerability in high-risk infants. PMID:25965343

  7. Thrombin-mediated activation of endogenous factor XI in plasma in the presence of physiological glycosaminoglycans occurs only with high concentrations of thrombin.

    PubMed

    Wuillemin, W A; Mertens, K; ten Cate, H; Hack, C E

    1996-02-01

    The variable bleeding tendency associated with a genetic deficiency of factor XI (FXI) and the lack of bleeding disorders in individuals with a genetic deficiency of factor XII (FXII) suggest an alternative mechanism for FXI activation in vivo. Recently, thrombin has been shown to activate FXI. However, in plasma this activation has been shown to occur only with exogenous FXI and a non-physiological cofactor (sulphatides), and the occurrence of this reaction in a plasma environment has been questioned. Using recently developed sensitive assays for FXIa-inhibitor complexes we found thrombin-mediated and FXII-dependent activation of endogenous FXI in plasma in the presence of heparan sulphate, heparin, dermatan sulphate or dextran sulphate. Using heparan sulphate, which is present in the human vascular system, activation of about 1-2% of plasma FXI was observed, however, only after addition of very high amounts (500 nmol/l) of human alpha-thrombin to FXII-deficient plasma (at a 1 to 4 final dilution). We conclude that endogenous FXI in plasma can be activated by thrombin in the presence of various glycosaminoglycans, including the physiological compounds heparan sulphate and dermatan sulphate, but only at very high concentrations of thrombin, corresponding to 100% prothrombin activation in undiluted plasma.

  8. A single naturally occurring 2'-O-methylation converts a TLR7- and TLR8-activating RNA into a TLR8-specific ligand.

    PubMed

    Jung, Stephanie; von Thülen, Tina; Laukemper, Viktoria; Pigisch, Stephanie; Hangel, Doris; Wagner, Hermann; Kaufmann, Andreas; Bauer, Stefan

    2015-01-01

    TLR7 and TLR8 recognize RNA from pathogens and lead to subsequent immune stimulation. Here we demonstrate that a single naturally occurring 2'-O-methylation within a synthetic 18s rRNA derived RNA sequence prevents IFN-α production, however secretion of proinflammatory cytokines such as IL-6 is not impaired. By analysing TLR-deficient plasmacytoid dendritic cells and performing HEK293 genetic complementation assays we could demonstrate that the single 2'-O-methylation containing RNA still activated TLR8 but not TLR7. Therefore this specific 2'-O-ribose methylation in rRNA converts a TLR7/TLR8 ligand to an exclusively TLR8-specific ligand. Interestingly, other modifications at this position such as 2'-O-deoxy or 2'-fluoro had no strong modulating effect on TLR7 or TLR8 activation suggesting an important role of 2'-O-methylation for shaping differential TLR7 or TLR8 activation. PMID:25785446

  9. COMPONENTS OF LASER SYSTEMS AND PROCESSES OCCURRING IN THEM: Quasiperiodic fluctuations and chaos in a gas-discharge laser with active mode locking

    NASA Astrophysics Data System (ADS)

    Mel'nikov, L. A.; Rabinovich, É. M.; Tuchin, Valerii V.

    1988-09-01

    An experimental investigation was made of the processes occurring on transition from active mode locking to chaotic free running of an He-Ne laser (1.15 μm). The appearance of quasiperiodic fluctuations and chaos was due to the formation of supermodes observed experimentally. A reduction of the depth of modulation induced higher supermodes. An asymmetry of the bifurcation diagram was observed as a result of a change in the sign of the mismatch between the modulation and beat frequencies. The nature of the processes occurring as a result of suppression of mode locking was fairly complex, but the following bifurcations could be identified: period doubling, tangential bifurcation, appearance of tori. A mapping relationship was obtained to describe changes in the pulse profile from one pass to the next during propagation in the laser resonator.

  10. Early and stable upregulation of collagen type II, collagen type I and YKL40 expression levels in cartilage during early experimental osteoarthritis occurs independent of joint location and histological grading

    PubMed Central

    Lorenz, Helga; Wenz, Wolfram; Ivancic, Mate; Steck, Eric; Richter, Wiltrud

    2005-01-01

    While morphologic and biochemical aspects of degenerative joint disease (osteoarthritis [OA]) have been elucidated by numerous studies, the molecular mechanisms underlying the progressive loss of articular cartilage during OA development remain largely unknown. The main focus of the present study was to gain more insight into molecular changes during the very early stages of mechanically induced cartilage degeneration and to relate molecular alterations to histological changes at distinct localizations of the joint. Studies on human articular cartilage are hampered by the difficulty of obtaining normal tissue and early-stage OA tissue, and they allow no progressive follow-up. An experimental OA model in dogs with a slow natural history of OA (Pond–Nuki model) was therefore chosen. Anterior cruciate ligament transection (ACLT) was performed on 24 skeletally mature dogs to induce joint instability resulting in OA. Samples were taken from different joint areas after 6, 12, 24 and 48 weeks, and gene expression levels of common cartilage molecules were quantified in relation to the histological grading (modified Mankin score) of adjacent tissue. Histological changes reflected early progressive degenerative OA. Soon after ACLT, chondrocytes responded to the altered mechanical conditions by significant and stable elevation of collagen type II, collagen type I and YKL40 expression, which persisted throughout the study. In contrast to the mild to moderate histological alterations, these molecular changes were not progressive and were independent of the joint localization (tibia, femur, lateral, medial) and the extent of matrix degeneration. MMP13 remained unaltered until 24 weeks, and aggrecan and tenascinC remained unaltered until 48 weeks after ACLT. These findings indicate that elevated collagen type II, collagen type I and YKL40 mRNA expression levels are early and sensitive measures of ACLT-induced joint instability independent of a certain grade of morphological

  11. Psychosocial Correlates of Physical and Sedentary Activities of Early Adolescent Youth

    PubMed Central

    Rusby, Julie C.; Westling, Erika; Crowley, Ryann; Light, John M.

    2013-01-01

    This study examines physical and sedentary activities of early adolescent boys and girls using Ecological Momentary Assessment (EMA), a method that can link mood and behaviors in specific social situations. Twenty-seven assessments were collected across seven days from 82 participating adolescents, three times in seventh grade and one time in eighth grade. Assessments were completed during nonschool hours when youth had “free time.” Gender differences, longitudinal trends, and associations of physical activities (PA) and small screen recreation (SSR) with moods and peer presence are examined. Boys were engaged in PA more than girls. Patterns of PA differed by gender; boys significantly decreased PA from seventh to eighth grade, whereas girls had increased PA only during the spring. PA was associated with happier mood and was more likely to occur in the presence of peers. SSR significantly increased from seventh grade to eighth grade for both boys and girls. SSR occurred more when youth were alone, and was not associated with mood. Neither PA nor SSR were more likely to occur during weekdays or weekends. Implications for intervention efforts to increase PA in youth are discussed. PMID:23640122

  12. "Naturally occurring asbestos

    NASA Astrophysics Data System (ADS)

    Cagnard, F.; Lahondère, D.; Blein, O.; Lahfid, A.; Wille, G.

    2012-04-01

    The term asbestos refers to six silicate minerals from amphibole and serpentine groups. By definition, it consists in bundles of thin and flexible long fibers, with high-tensile strength, and chemical and heat resistance. In contrast to asbestos found within commercial products and mining, the specific term ''naturally occurring asbestos'' (NOA) refers to asbestiform minerals occurring within rocks or soils that can be released by human activities or weathering processes. The fact that the exposure to asbestos is related to lung pathologies is now widely demonstrated (e.g. asbestosis, mesothelioma and lung cancer). However, if health risks associated with exposure to NOA exist, they are not yet well documented. The crystallization of natural asbestos occurs in specific Mg-rich lithologies associated with peculiar structural and metamorphic conditions. By recognizing and combining such specific geologic criteria, the presence or the absence of asbestos in bedrock terrains can be reasonably predicted and maps of NOA hazard can be drawn. We present here new results of geological mapping and petrological study concerning the evaluation of the NOA hazard in the Alps and Corsica, in France. The three folds approach consists in (1) a determination of lithologies with potential NOA from a bibliographic compilation and extraction of target zones from a geological geodatabase (2) a geological mapping of the target zones followed by a petrological characterization of sampled asbestiform minerals in the laboratory (optical microscopy, TEM, SEM, and Raman spectroscopy technics), and (3) the drawing of the final map of NOA hazard, at regional-scale. Occurrence criteria can be retained as follows: 1. NOA are abundant in the internal zones of the Alps and Corsica, especially within ophiolitic complexes. Natural asbestos are mostly concentrated within ultramafic rocks but can also occur within basic lithologies such as Mg-metagabbros, metabasalts and meta-pillow-lavas, 2. Asbestos

  13. Systemic endothelial activation occurs in both mild and severe malaria. Correlating dermal microvascular endothelial cell phenotype and soluble cell adhesion molecules with disease severity.

    PubMed

    Turner, G D; Ly, V C; Nguyen, T H; Tran, T H; Nguyen, H P; Bethell, D; Wyllie, S; Louwrier, K; Fox, S B; Gatter, K C; Day, N P; Tran, T H; White, N J; Berendt, A R

    1998-06-01

    Fatal Plasmodium falciparum malaria is accompanied by systemic endothelial activation. To study endothelial activation directly during malaria and sepsis in vivo, the expression of cell adhesion molecules on dermal microvascular endothelium was examined in skin biopsies and correlated with plasma levels of soluble (circulating) ICAM-1, E-selectin, and VCAM-1 and the cytokine tumor necrosis factor (TNF)-alpha. Skin biopsies were obtained from 61 cases of severe malaria, 42 cases of uncomplicated malaria, 10 cases of severe systemic sepsis, and 17 uninfected controls. Systemic endothelial activation, represented by the up-regulation of inducible cell adhesion molecules (CAMs) on endothelium and increased levels of soluble CAMs (sCAMs), were seen in both severe and uncomplicated malaria and sepsis when compared with uninfected controls. Plasma levels of sICAM-1, sVCAM-1, and sE-selectin correlated positively with the severity of malaria whereas TNF-alpha was raised nonspecifically in malaria and sepsis. Immunohistochemical evidence of endothelial activation in skin biopsies did not correlate with sCAM levels or disease severity. This indicates a background of systemic endothelial activation, which occurs in both mild and severe malaria and sepsis. The levels of sCAMs in malaria are thus not an accurate reflection of endothelial cell expression of CAMs in a particular vascular bed, and other factors must influence their levels during disease.

  14. Systemic endothelial activation occurs in both mild and severe malaria. Correlating dermal microvascular endothelial cell phenotype and soluble cell adhesion molecules with disease severity.

    PubMed Central

    Turner, G. D.; Ly, V. C.; Nguyen, T. H.; Tran, T. H.; Nguyen, H. P.; Bethell, D.; Wyllie, S.; Louwrier, K.; Fox, S. B.; Gatter, K. C.; Day, N. P.; Tran, T. H.; White, N. J.; Berendt, A. R.

    1998-01-01

    Fatal Plasmodium falciparum malaria is accompanied by systemic endothelial activation. To study endothelial activation directly during malaria and sepsis in vivo, the expression of cell adhesion molecules on dermal microvascular endothelium was examined in skin biopsies and correlated with plasma levels of soluble (circulating) ICAM-1, E-selectin, and VCAM-1 and the cytokine tumor necrosis factor (TNF)-alpha. Skin biopsies were obtained from 61 cases of severe malaria, 42 cases of uncomplicated malaria, 10 cases of severe systemic sepsis, and 17 uninfected controls. Systemic endothelial activation, represented by the up-regulation of inducible cell adhesion molecules (CAMs) on endothelium and increased levels of soluble CAMs (sCAMs), were seen in both severe and uncomplicated malaria and sepsis when compared with uninfected controls. Plasma levels of sICAM-1, sVCAM-1, and sE-selectin correlated positively with the severity of malaria whereas TNF-alpha was raised nonspecifically in malaria and sepsis. Immunohistochemical evidence of endothelial activation in skin biopsies did not correlate with sCAM levels or disease severity. This indicates a background of systemic endothelial activation, which occurs in both mild and severe malaria and sepsis. The levels of sCAMs in malaria are thus not an accurate reflection of endothelial cell expression of CAMs in a particular vascular bed, and other factors must influence their levels during disease. Images Figure 1 PMID:9626052

  15. Zephycandidine A, the First Naturally Occurring Imidazo[1,2-f]phenanthridine Alkaloid from Zephyranthes candida, Exhibits Significant Anti-tumor and Anti-acetylcholinesterase Activities

    PubMed Central

    Zhan, Guanqun; Qu, Xiaolan; Liu, Junjun; Tong, Qingyi; Zhou, Junfei; Sun, Bin; Yao, Guangmin

    2016-01-01

    Zephycandidine A (1), the first naturally occurring imidazo[1,2-f]phenanthridine alkaloid, was isolated from Zephyranthes candida (Amaryllidaceae). The structure of 1 was elucidated by spectroscopic analyses and NMR calculation, and a plausible biogenetic pathway for zephycandidine A (1) was proposed. Zephycandidine A (1) exhibited significant cytotoxicity against five cancer cell lines with IC50 values ranging from 1.98 to 7.03 μM with selectivity indices as high as 10 when compared to the normal Beas-2B cell. Further studies suggested that zephycandidine A (1) induces apoptosis in leukemia cells by the activation of caspase-3, upregulation of Bax, downregulation of Bcl-2, and degradation of PARP expression. In addition, zephycandidine A (1) showed acetylcholinesterase (AChE) inhibitory activity, and the docking studies of zephycandidine A (1) and galanthamine (2) with AChE revealed that interactions with W286 and Y337 are necessary. PMID:27658482

  16. Zephycandidine A, the First Naturally Occurring Imidazo[1,2-f]phenanthridine Alkaloid from Zephyranthes candida, Exhibits Significant Anti-tumor and Anti-acetylcholinesterase Activities

    NASA Astrophysics Data System (ADS)

    Zhan, Guanqun; Qu, Xiaolan; Liu, Junjun; Tong, Qingyi; Zhou, Junfei; Sun, Bin; Yao, Guangmin

    2016-09-01

    Zephycandidine A (1), the first naturally occurring imidazo[1,2-f]phenanthridine alkaloid, was isolated from Zephyranthes candida (Amaryllidaceae). The structure of 1 was elucidated by spectroscopic analyses and NMR calculation, and a plausible biogenetic pathway for zephycandidine A (1) was proposed. Zephycandidine A (1) exhibited significant cytotoxicity against five cancer cell lines with IC50 values ranging from 1.98 to 7.03 μM with selectivity indices as high as 10 when compared to the normal Beas-2B cell. Further studies suggested that zephycandidine A (1) induces apoptosis in leukemia cells by the activation of caspase-3, upregulation of Bax, downregulation of Bcl-2, and degradation of PARP expression. In addition, zephycandidine A (1) showed acetylcholinesterase (AChE) inhibitory activity, and the docking studies of zephycandidine A (1) and galanthamine (2) with AChE revealed that interactions with W286 and Y337 are necessary.

  17. Active compressive intraoceanic deformation: early stages of ophiolites emplacement?

    NASA Astrophysics Data System (ADS)

    Chamot-Rooke, Nicolas; Delescluse, Matthias; Montési, Laurent

    2010-05-01

    investigate the very early stages of formation of faulted oceanic bodies that may further be incorporated into mountain belts as ophiolites. They allow to discuss rates and duration of deformation, diffuse vs localized deformation, re-activation vs neo-formed faults, serpentinization and thermal regime, spacing of minor and major thrust faults. Delescluse, M., L. G. J. Montesi, and N. Chamot-Rooke (2008) Fault reactivation and selective abandonment in the oceanic lithosphere. Geophys. Res. Lett., v. 35. Delescluse, M., and N. Chamot-Rooke (2008) Serpentinization pulse in the actively deforming Central Indian Basin. Earth Planet. Sci. Lett., v. 276, p. 140-151. Eittreim, S. L., and J. Ewing (1972), Mid-Plate Tectonics in the Indian Ocean, J. Geophys. Res., 77(32), 6413-6421.

  18. Early events of human T lymphocyte activation are associated with type I protein kinase A activity.

    PubMed Central

    Laxminarayana, D; Berrada, A; Kammer, G M

    1993-01-01

    Human T lymphocytes possess both the type I and II isozymes of protein kinase A (PKA). The type I (PKA-I) isozyme is predominantly associated with the plasma membrane, whereas the type II (PKA-II) isozyme is primarily localized to the cytosol. Because the functions of both PKA-I and PKA-II isozymes in the biochemical events of T lymphocyte activation have not been clearly elucidated, we tested the hypothesis that very early events of normal human T lymphocyte activation are mediated by the PKA-I and/or PKA-II isozyme(s). Fresh normal human T cells and a normal human CD4+ T cell line (GK606) activated with anti-CD3-epsilon and recombinant interleukin 1 alpha (rIL-1 alpha) exhibited a peak six- to sevenfold increase of PKA phosphotransferase activity at 5 min that returned to baseline by 60 min. Similarly, both fresh T cells and the T cell line activated by phorbol myristate acetate and ionomycin demonstrated a peak eightfold increase of PKA activity by 15 min that returned toward baseline by 60 min. Chromatographic separation of the PKA isozymes and quantification of phosphotransferase activities after T cell activation by either agonist pair showed preferential activation of the PKA-I isozyme, resulting in a significant reduction in the ratio of PKA-I to PKA-II isozyme activity from 3.1:1-6.2:1 to 1.1:1-3.2:1. PKA-I isozyme activation resulted in the release of free catalytic (C) subunit, an increase in C subunit phosphotransferase activity, and the phosphorylation of T cell plasma membrane-associated proteins, p14, p17, p20, p21, p38, and p48. However, activation of the PKA-I isozyme did not appear to be required for the transcription of IL-2 mRNA, an event necessary for mitosis. These data indicate that ligand-induced T cell activation is associated with rapid activation of the PKA-I, but not PKA-II, isozyme that results in phosphorylation of plasma membrane-associated proteins. The involvement of the PKA-I isozyme during the very early events of T cell

  19. SALSA: A Regulator of the Early Steps of Complement Activation on Mucosal Surfaces

    PubMed Central

    Reichhardt, Martin Parnov; Meri, Seppo

    2016-01-01

    Complement is present mainly in blood. However, following mechanical damage or inflammation, serous exudates enter the mucosal surfaces. Here, the complement proteins interact with other endogenous molecules to keep microbes from entering the parenteral tissues. One of the mucosal proteins known to interact with the early complement components of both the classical and the lectin pathway is the salivary scavenger and agglutinin (SALSA). SALSA is also known as deleted in malignant brain tumors 1 and gp340. It is found both attached to the epithelium and secreted into the surrounding fluids of most mucosal surfaces. SALSA has been shown to bind directly to C1q, mannose-binding lectin, and the ficolins. Through these interactions SALSA regulates activation of the complement system. In addition, SALSA interacts with surfactant proteins A and D, secretory IgA, and lactoferrin. Ulcerative colitis and Crohn’s disease are examples of diseases, where complement activation in mucosal tissues may occur. This review describes the latest advances in our understanding of how the early complement components interact with the SALSA molecule. Furthermore, we discuss how these interactions may affect disease propagation on mucosal surfaces in immunological and inflammatory diseases. PMID:27014265

  20. Characterization of cultivar differences in beta-1,3 glucanase gene expression, glucanase activity and fruit pulp softening rates during fruit ripening in three naturally occurring banana cultivars.

    PubMed

    Roy Choudhury, Swarup; Roy, Sujit; Sengupta, Dibyendu N

    2009-11-01

    beta-1,3 glucanase (E.C.3.2.1.39) is the key enzyme involved in the hydrolytic cleavage of 1,3 beta-D glucosidic linkages in beta-1,3 glucans. This work describes a comparative analysis of expression patterns of beta-1,3 glucanase gene in relation to changes in fruit pulp softening rates in three banana cultivars, Rasthali (AAB), Kanthali (AB), and Monthan (ABB). Analysis of transcript and protein levels of beta-1,3 glucanase gene during ripening revealed differential timing in expression of the gene which correlated well with the variation in enzymatic activity of glucanase and fruit pulp softening rates in the three cultivars. Exogenously applied ethylene strongly induced beta-1,3 glucanase expression during the early ripening days in Rasthali, while the expression of the gene was marginally stimulated following ethylene treatment in preclimacteric Kanthali fruit. Conversely, in Monthan, beta-1,3 glucanase expression was very low throughout the ripening stages, and ethylene treatment did not induce the expression of the gene in this cultivar. Analysis of glucanase activity using protein extracts from unripe and ripe fruit of Monthan with crude cell wall polysaccharide fractions (used as substrate) indicated that the natural substrate for glucanase remained almost unutilized in this cultivar due to low in vivo glucanase activity. Furthermore, the recombinant beta-1,3 glucanase protein, overexpressed in E. coli, showed requirement for substrates with contiguous beta-1,3 linkages for optimal activity. Overall, our results provide new information on the expression profile of beta-1,3 glucanase gene in connection with the pattern of changes in fruit firmness at the physiological and molecular levels during ripening in three banana cultivars. PMID:19697038

  1. Default Mode Network Activity Predicts Early Memory Decline in Healthy Young Adults Aged 18-31.

    PubMed

    Nelson, Steven M; Savalia, Neil K; Fishell, Andrew K; Gilmore, Adrian W; Zou, Fan; Balota, David A; McDermott, Kathleen B

    2016-08-01

    Functional magnetic resonance imaging (fMRI) research conducted in healthy young adults is typically done with the assumption that this sample is largely homogeneous. However, studies from cognitive psychology suggest that long-term memory and attentional control begin to diminish in the third decade of life. Here, 100 participants between the ages of 18 and 31 learned Lithuanian translations of English words in an individual differences study using fMRI. Long-term memory ability was operationalized for each participant by deriving a memory score from 3 convergent measures. Age of participant predicted memory score in this cohort. In addition, degree of deactivation during initial encoding in a set of regions occurring largely in the default mode network (DMN) predicted both age and memory score. The current study demonstrates that early memory decline may partially be accounted for by failure to modulate activity in the DMN.

  2. The influences of impact interface, muscle activity, and knee angle on impact forces and tibial and femoral accelerations occurring after external impacts.

    PubMed

    Potthast, Wolfgang; Brüggemann, Gert-Peter; Lundberg, Arne; Arndt, Anton

    2010-02-01

    The purpose of this study was to quantify relative contributions of impact interface, muscle activity, and knee angle to the magnitudes of tibial and femoral accelerations occurring after external impacts. Impacts were initiated with a pneumatically driven impacter under the heels of four volunteers. Impact forces were quantified with a force sensor. Segmental accelerations were measured with bone mounted accelerometers. Experimental interventions were hard and soft shock interfaces, different knee angles (0 degrees, 20 degrees, 40 degrees knee flexion), and muscular preactivation (0%, 30%, 60% of maximal voluntary contraction) of gastrocnemii, hamstrings, and quadriceps. Greater knee flexion led to lower impact forces and higher tibial accelerations. Increased muscular activation led to higher forces and lower tibial accelerations. The softer of the two shock interfaces under study reduced both parameters. The effects on accelerations and forces through the activation and knee angle changes were greater than the effect of interface variations. The hardness of the two shock interfaces explained less than 10% of the variance of accelerations and impact forces, whereas knee angle changes explained 25-29%, and preactivation changes explained 35-48% of the variances. It can be concluded that muscle force and knee joint angle have greater effects in comparison with interface hardness on the severity of shocks on the lower leg.

  3. Structure-activity relationship studies of 5,7-dihydroxyflavones as naturally occurring inhibitors of cell proliferation in human leukemia HL-60 cells.

    PubMed

    Ninomiya, Masayuki; Nishida, Kyohei; Tanaka, Kaori; Watanabe, Kunitomo; Koketsu, Mamoru

    2013-07-01

    Flavonoids are widely occurring polyphenols that are found in plants. The aim of this study was to investigate the structure-activity relationships of 5,7-dihydroxyflavones, with a focus on the effect of B ring structure substitution on the antiproliferative effects of the compounds in human leukemia HL-60 cells. We prepared a series of 5,7-dihydroxyflavones and evaluated their ability to inhibit the proliferation of HL-60 cells by using the MTT assay. The apoptosis- and cell differentiation-inducing ability of the most potent flavones were investigated using staining and morphological analyses. This study explored the antileukemic and chemopreventive potency of 5,7-dihydroxyflavones, particularly diosmetin and chrysoeriol, which have both hydroxy and methoxy groups on the B ring.

  4. SUMOylation of the mitochondrial fission protein Drp1 occurs at multiple nonconsensus sites within the B domain and is linked to its activity cycle

    PubMed Central

    Figueroa-Romero, Claudia; Iñiguez-Lluhí, Jorge A.; Stadler, Julia; Chang, Chuang-Rung; Arnoult, Damien; Keller, Peter J.; Hong, Yu; Blackstone, Craig; Feldman, Eva L.

    2009-01-01

    Dynamin-related protein (Drp) 1 is a key regulator of mitochondrial fission and is composed of GTP-binding, Middle, insert B, and C-terminal GTPase effector (GED) domains. Drp1 associates with mitochondrial fission sites and promotes membrane constriction through its intrinsic GTPase activity. The mechanisms that regulate Drp1 activity remain poorly understood but are likely to involve reversible post-translational modifications, such as conjugation of small ubiquitin-like modifier (SUMO) proteins. Through a detailed analysis, we find that Drp1 interacts with the SUMO-conjugating enzyme Ubc9 via multiple regions and demonstrate that Drp1 is a direct target of SUMO modification by all three SUMO isoforms. While Drp1 does not harbor consensus SUMOylation sequences, our analysis identified2 clusters of lysine residues within the B domain that serve as noncanonical conjugation sites. Although initial analysis indicates that mitochondrial recruitment of ectopically expressed Drp1 in response to staurosporine is unaffected by loss of SUMOylation, we find that Drp1 SUMOylation is enhanced in the context of the K38A mutation. This dominant-negative mutant, which is deficient in GTP binding and hydrolysis, does not associate with mitochondria and prevents normal mitochondrial fission. This finding suggests that SUMOylation of Drp1 is linked to its activity cycle and is influenced by Drp1 localization.—Figueroa-Romero, C., Iñiguez-Lluhí, J. A., Stadler, J., Chang, C.-R., Arnoult, D., Keller, P. J., Hong, Y., Blackstone, C., Feldman, E. L. SUMOylation of the mitochondrial fission protein Drp1 occurs at multiple nonconsensus sites within the B domain and is linked to its activity cycle. PMID:19638400

  5. Project Spectrum: Early Learning Activities. Project Zero Frameworks for Early Childhood Education, Volume 2.

    ERIC Educational Resources Information Center

    Chen, Jie-Qi, Ed.; Isberg, Emily, Ed.; Krechevsky, Mara, Ed.

    Project Spectrum is a collaborative research and development project that offers an alternative approach to assessment and curriculum development for preschool and early primary years. The project, based on Howard Gardner's multiple intelligences theory and David Henry Feldman's nonuniversal development theory, emphasizes observing children…

  6. Early Childhood Policy Focus: Healthy Eating and Physical Activity. Early Childhood Highlights. Volume 2, Issue 3

    ERIC Educational Resources Information Center

    Murphey, David; Mackintosh, Bonnie; McCoy-Roth, Marci

    2011-01-01

    The importance of good nutrition and exercise is well known, and parents have long worried about their children's diets and envied their high energy levels. Like so many life style habits, patterns of nutrition and exercise behaviors are typically established in early childhood. Poor diet and lack of exercise contribute to obesity, which has been…

  7. Early Childhood Adventures in Peacemaking: A Conflict Resolution Activity Guide for Early Childhood Educators. Second Edition.

    ERIC Educational Resources Information Center

    Kreidler, William J.; Whittall, Sandy Tsubokawa

    This early childhood curriculum (ages 3-6) uses games, music, art, drama, and storytelling to teach young children effective, nonviolent ways to resolve conflicts and provides caregivers with tools for helping young children develop key conflict resolution skills. Following an introductory chapter, Chapter 2 provides guidance in assessing the…

  8. Move to Learn, Learn to Move: Prioritizing Physical Activity in Early Childhood Education Programming

    ERIC Educational Resources Information Center

    Lu, Chunlei; Montague, Brandi

    2016-01-01

    The global childhood trend towards obesity and unhealthy lifestyles is a growing concern. Childcare settings have been identified as the most influential factors for children's physical activity, and physical activity habits are better formed and maintained if started in early childhood. As a result, early childhood education environments are in…

  9. Affordances for Risk-Taking and Physical Activity in Australian Early Childhood Education Settings

    ERIC Educational Resources Information Center

    Little, Helen; Sweller, Naomi

    2015-01-01

    Motor competence and physical activity (PA) patterns are established during the early childhood years. Early childhood education (ECE) settings are an important context for children's engagement in physically active play. This paper reports the findings from an online survey examining resources, spaces and affordances for PA and risk-taking in…

  10. Activation of Protease Activated Receptor 2 by Exogenous Agonist Exacerbates Early Radiation Injury in Rat Intestine

    SciTech Connect

    Wang Junru; Boerma, Marjan; Kulkarni, Ashwini; Hollenberg, Morley D.; Hauer-Jensen, Martin

    2010-07-15

    Purpose: Protease-activated receptor-2 (PAR{sub 2}) is highly expressed throughout the gut and regulates the inflammatory, mitogenic, fibroproliferative, and nociceptive responses to injury. PAR{sub 2} is strikingly upregulated and exhibits increased activation in response to intestinal irradiation. We examined the mechanistic significance of radiation enteropathy development by assessing the effect of exogenous PAR{sub 2} activation. Methods and Materials: Rat small bowel was exposed to localized single-dose radiation (16.5 Gy). The PAR{sub 2} agonist (2-furoyl-LIGRLO-NH{sub 2}) or vehicle was injected intraperitoneally daily for 3 days before irradiation (before), for 7 days after irradiation (after), or both 3 days before and 7 days after irradiation (before-after). Early and delayed radiation enteropathy was assessed at 2 and 26 weeks after irradiation using quantitative histologic examination, morphometry, and immunohistochemical analysis. Results: The PAR{sub 2} agonist did not elicit changes in the unirradiated (shielded) intestine. In contrast, in the irradiated intestine procured 2 weeks after irradiation, administration of the PAR{sub 2} agonist was associated with more severe mucosal injury and increased intestinal wall thickness in all three treatment groups (p <.05) compared with the vehicle-treated controls. The PAR{sub 2} agonist also exacerbated the radiation injury score, serosal thickening, and mucosal inflammation (p <.05) in the before and before-after groups. The short-term exogenous activation of PAR{sub 2} did not affect radiation-induced intestinal injury at 26 weeks. Conclusion: The results of the present study support a role for PAR{sub 2} activation in the pathogenesis of early radiation-induced intestinal injury. Pharmacologic PAR{sub 2} antagonists might have the potential to reduce the intestinal side effects of radiotherapy and/or as countermeasures in radiologic accidents or terrorism scenarios.

  11. [Photoreactivating Activity of Bioluminescence: Repair of UV-damaged DNA of Escherichia coli Occurs with Assistance of lux-Genes of Marine Bacteria].

    PubMed

    Zavilgelsky, G B; Melkina, O E; Kotova, V Yu; Konopleva, M N; Manukhov, I V; Pustovoit, K Ss

    2015-01-01

    The UV resistance of luminescent bacteria Escherichia coli AB1886 uvrA6 (pLeo1) containing the plasmid with luxCDABE genes of marine bacteria Photobacterium leiognathi is approximately two times higher than the UV resistance of non-luminous bacteria E. coli AB1886 uvrA6. Introduction of phr::kan(r) mutations (a defect in the functional activity of photolyase) into the genome of E. coli AB1886 uvrA6 (pLeo1) completely removes the high UV resistance of the cells. Therefore, photoreactivation that involves bacterial photolyase contributes mainly to the bioluminescence-induced DNA repair. It is shown that photoreactivating activity of bioluminescence of P. leiognathi is about 2.5 times lower compared with that one induced by a light source with λ > 385 nm. It is also shown that an increase in the bioluminescence intensity, induced by UV radiation in E. coli bacterial cells with a plasmid containing the luxCD ABE genes under RecA-LexA-regulated promoters, occurs only 25-30 min later after UV irradiation of cells and does not contribute to DNA repair. A quorum sensing regulatory system is not involved in the DNA repair by photolyase.

  12. An Activity-Based Approach to Early Intervention. Third Edition

    ERIC Educational Resources Information Center

    Pretti-Frontczak, Kristie; Bricker, Diane

    2004-01-01

    How can early childhood professionals seamlessly link assessment, goal development, intervention, and evaluation for children from birth to age 5--while developing individualized IEP/IFSP goals, creating multiple and varied learning opportunities, and working as a team? The third edition of this highly respected resource has the answers. A classic…

  13. SARS coronavirus spike protein-induced innate immune response occurs via activation of the NF-kappaB pathway in human monocyte macrophages in vitro.

    PubMed

    Dosch, Susan F; Mahajan, Supriya D; Collins, Arlene R

    2009-06-01

    A purified recombinant spike (S) protein was studied for its effect on stimulating human peripheral blood monocyte macrophages (PBMC). We examined inflammatory gene mRNA abundances found in S protein-treated PBMC using gene arrays. We identified differential mRNA abundances of genes with functional properties associated with antiviral (CXCL10) and inflammatory (IL-6 and IL-8) responses. We confirmed cytokine mRNA increases by real-time quantitative(q) RT-PCR or ELISA. We further analyzed the sensitivity and specificity of the prominent IL-8 response. By real-time qRT-PCR, S protein was shown to stimulate IL-8 mRNA accumulation in a dose dependent manner while treatment with E protein did not. Also, titration of S protein-specific production and secretion of IL-8 by ELISA showed that the dose of 5.6nM of S produced a significant increase in IL-8 (p=0.003) compared to mock-treated controls. The increase in IL-8 stimulated by a concentration of 5.6nM of S was comparable to concentrations seen for S protein binding to ACE2 or to neutralizing monoclonal antibody suggesting a physiological relevance. An NF-kappaB inhibitor, TPCK (N-Tosyl-L-Phenylalanine Chloromethyl Ketone) could suppress IL-8 production and secretion in response to S protein in PBMC and THP-1 cells and in HCoV-229E virus-infected PBMC. Activation and translocation of NF-kappaB was shown to occur rapidly following exposure of PBMC or THP-1 cells to S protein using a highly sensitive assay for active nuclear NF-kappaB p65 transcription factor. The results further suggested that released or secreted S protein could activate blood monocytes through recognition by toll-like receptor (TLR)2 ligand.

  14. Co-Occurring Disorders

    MedlinePlus

    ... Care of You Top Ten Freshman Year Issues Alcohol, Substance Abuse and Depression Winter Break Survival Tips for College Students Implementing ... supporters and consumers in the mental health field. Alcohol and Drug Abuse, Addiction and Co-occurring Disorders: Co-occurring ... In Crisis? Call ...

  15. Early Human Activity (pre-332 BC) in Alexandria, Egypt: New findings in Eastern Harbor Cores

    NASA Astrophysics Data System (ADS)

    Stanley, J.; Landau, E. A.

    2005-12-01

    Historians have long postulated that a settlement called Rhakotis was present on Egypt's Mediterranean coast in the area subsequently occupied by the city of Alexandria. To date, however, the precise position of that site has not been located in the immediate area of the city founded by Alexander the Great. Also undefined are the earliest phases of occupation that pre-date Alexandria on Pharos Island and in the harbour area. A geoarchaeological project emphasizing sediment cores in Alexandria's Eastern Harbour now provides evidence of human occupation adjacent to these settings prior to establishment of Greece's great port in 332 BC. A radiocarbon-dated stratigraphic unit, defined as Middle Sand (III) and older than the 4th century BC, includes locally produced ceramics, along with rock fragments of non-local origin, and increased content of sand-sized heavy mineral and organic matter. Together, these date at least to Egypt's Late Dynastic Period (712-332 BC). Moreover, the geographic positions of core sites containing these markers indicate that early habitation occurred both at Pharos Island and on the mainland where the future Alexandria would be built. New findings in cores recovered in this marine environment are adding to knowledge of both natural processes and effects of human activity in early Alexandria.

  16. Early intracardiac thrombosis in preterm infants and thrombolysis with recombinant tissue type plasminogen activator

    PubMed Central

    Ferrari, F; Vagnarelli, F; Gargano, G; Roversi, M; Biagioni, O; Ranzi, A; Cavazzuti, G

    2001-01-01

    OBJECTIVES—To determine the incidence of catheter related thrombosis and to test the efficacy of recombinant tissue type plasminogen activator (rt-PA) in preterm infants.
STUDY DESIGN—From January 1995 to December 1998, echocardiography was performed in the first few days of life in 76 very low birthweight (⩽ 1500 g) infants out of a total of 147 having an umbilical catheter placed. When intracardiac thrombosis was diagnosed, rt-PA infusion was performed.
RESULTS—Four infants (5%) developed an intracardiac thrombosis during the first few days of life. In three of them, rt-PA at a dose of 0.4-0.5 mg/kg in a 20-30 minute bolus led to dissolution of the clot. One patient received a three hour infusion after the bolus, at a dose of 0.1 mg/kg/h, with resolution of the thrombus. No systemic effects were observed after rt-PA infusion.
CONCLUSIONS—Early thrombosis may occur as a complication of umbilical catheterisation in preterm infants; early echocardiographic detection of this disorder allows complete, safe, and rapid lysis with rt-PA.

 PMID:11420328

  17. Early-Late Heterobimetallic Complexes Linked by Phosphinoamide Ligands. Tuning Redox Potentials and Small Molecule Activation

    SciTech Connect

    Thomas, Christine M.

    2015-08-01

    Recent attention in the chemical community has been focused on the energy efficient and environmentally benign conversion of abundant small molecules (CO2, H2O, etc.) to useful liquid fuels. This project addresses these goals by examining fundamental aspects of catalyst design to ultimately access small molecule activation processes under mild conditions. Specifically, Thomas and coworkers have targetted heterobimetallic complexes that feature metal centers with vastly different electronic properties, dictated both by their respective positions on the periodic table and their coordination environment. Unlike homobimetallic complexes featuring identical or similar metals, the bonds between metals in early/late heterobimetallics are more polarized, with the more electron-rich late metal center donating electron density to the more electron-deficient early metal center. While metal-metal bonds pose an interesting strategy for storing redox equivalents and stabilizing reactive metal fragments, the polar character of metal-metal bonds in heterobimetallic complexes renders these molecules ideally poised to react with small molecule substrates via cleavage of energy-rich single and double bonds. In addition, metal-metal interactions have been shown to dramatically affect redox potentials and promote multielectron redox activity, suggesting that metal-metal interactions may provide a mechanism to tune redox potentials and access substrate reduction/activation at mild overpotentials. This research project has provided a better fundamental understanding of how interactions between transition metals can be used as a strategy to promote and/or control chemical transformations related to the clean production of fuels. While this project focused on the study of homogeneous systems, it is anticipated that the broad conclusions drawn from these investigations will be applicable to heterogeneous catalysis as well, particularly on heterogeneous processes that occur at interfaces in

  18. Keratinocyte nicotinic acetylcholine receptor activation modulates early TLR2-mediated wound healing responses.

    PubMed

    Kishibe, Mari; Griffin, Tina M; Radek, Katherine A

    2015-11-01

    The cholinergic anti-inflammatory pathway spans several macro- and micro-environments to control inflammation via α7 nicotinic acetylcholine receptors (nAChRs). Physiologic inflammation is necessary for normal wound repair and is triggered, in part, via Toll-like receptors (TLRs). Here, we demonstrate that keratinocyte nAChR activation dampens TLR2-mediated migration and pro-inflammatory cytokine and antimicrobial peptide (AMP) production, which is restored by a α7-selective nAChR antagonist. The mechanism of this response occurs by blocking the NF-κB and Erk1/2 pathway during early and late wound healing. In a mouse model of Staphylococcus aureus wound infection, topical nAChR activation reduces wound AMP and TLR2 production to augment bacterial survival in wild-type mice. These findings suggest that aberrant α7 nAChR activation may impair normal wound healing responses, and that pharmacologic administration of topical nAChR antagonists may improve wound healing outcomes in wounds necessitating a more robust inflammatory response.

  19. Early Activity in Broca's Area During Reading Reflects Fast Access to Articulatory Codes From Print.

    PubMed

    Klein, Michael; Grainger, Jonathan; Wheat, Katherine L; Millman, Rebecca E; Simpson, Michael I G; Hansen, Peter C; Cornelissen, Piers L

    2015-07-01

    Prior evidence for early activity in Broca's area during reading may reflect fast access to articulatory codes in left inferior frontal gyrus pars opercularis (LIFGpo). We put this hypothesis to test using a benchmark for articulatory involvement in reading known as the masked onset priming effect (MOPE). In masked onset priming, briefly presented pronounceable strings of letters that share an initial phoneme with subsequently presented target words (e.g., gilp-GAME) facilitate word naming responses compared with unrelated primes (dilp-GAME). Crucially, these priming effects only occur when the task requires articulation (naming), and not when it requires lexical decisions. A standard explanation of masked onset priming is that it reflects fast computation of articulatory output codes from letter representations. We therefore predicted 1) that activity in left IFG pars opercularis would be modulated by masked onset priming, 2) that priming-related modulation in LIFGpo would immediately follow activity in occipital cortex, and 3) that this modulation would be greater for naming than for lexical decision. These predictions were confirmed in a magnetoencephalography (MEG) priming study. MOPEs emerged in left IFG at ∼100 ms posttarget onset, and the priming effects were more sustained when the task involved articulation.

  20. Transport through the yeast endocytic pathway occurs through morphologically distinct compartments and requires an active secretory pathway and Sec18p/N-ethylmaleimide-sensitive fusion protein.

    PubMed Central

    Hicke, L; Zanolari, B; Pypaert, M; Rohrer, J; Riezman, H

    1997-01-01

    Molecules travel through the yeast endocytic pathway from the cell surface to the lysosome-like vacuole by passing through two sequential intermediates. Immunofluorescent detection of an endocytosed pheromone receptor was used to morphologically identify these intermediates, the early and late endosomes. The early endosome is a peripheral organelle that is heterogeneous in appearance, whereas the late endosome is a large perivacuolar compartment that corresponds to the prevacuolar compartment previously shown to be an endocytic intermediate. We demonstrate that inhibiting transport through the early secretory pathway in sec mutants quickly impedes transport from the early endosome. Treatment of sensitive cells with brefeldin A also blocks transport from this compartment. We provide evidence that Sec18p/N-ethylmaleimide-sensitive fusion protein, a protein required for membrane fusion, is directly required in vivo for forward transport early in the endocytic pathway. Inhibiting protein synthesis does not affect transport from the early endosome but causes endocytosed proteins to accumulate in the late endosome. As newly synthesized proteins and the late steps of secretion are not required for early to late endosome transport, but endoplasmic reticulum through Golgi traffic is, we propose that efficient forward transport in the early endocytic pathway requires delivery of lipid from secretory organelles to endosomes. Images PMID:9017592

  1. Antioxidant compounds and antioxidant activity in "early potatoes".

    PubMed

    Leo, Lucia; Leone, Antonella; Longo, Cristiano; Lombardi, Domenico Antonio; Raimo, Francesco; Zacheo, Giuseppe

    2008-06-11

    The antioxidant content and the antioxidant capacity of both hydrophilic and lipophilic antioxidant extracts from four "early potato" cultivars, grown in two different locations (Racale and Monteroni), were examined. There was a considerable variation in carotenoid content and weak differences in the ascorbic acid concentration of the examined cultivars of "early potato" and between the harvested locations. An increase in both methanol/water (8:2 v/v) and phosphate buffer soluble (PBS) free phenols (70%) and bound phenols (28%) in the extracts from the cultivars grown at Racale site was found and discussed. Examination of individual phenols revealed that chlorogenic acid and catechin were the major phenols present in potato tuber extracts; a moderate amount of caffeic acid and ferulic acid was also detected. The total equivalent antioxidant capacity (TEAC) was higher in the Racale extracts and a highly positive linear relationship ( R (2) = 0.8193) between TEAC values and total phenolic content was observed. The oxyradical scavenging capacity (TOSC) of methanol/water and PBS extracts of peel and whole potatoes against the reactive oxygen species (ROS) peroxyl radicals, peroxynitrite, and hydroxyl radicals was also analyzed. A highly significant linear correlation ( R (2) = 0.9613) between total antioxidant capacity (as a sum of peroxyl radicals + peroxynitrite) and total phenol content of methanol/water extracts was established. Moreover, proliferation of human mammalian cancer (MCF-7) cells was significantly inhibited in a dose-dependent manner after exposure to potato extracts. These data can be useful for "early potato" tuber characterization and suggest that the "early potato" has a potential as a dietary source of antioxidants.

  2. Increasing late winter-early spring fire activity in Northern Spain: climate change or human footprint?

    NASA Astrophysics Data System (ADS)

    Carracedo Martín, Virginia; García Codron, Juan Carlos; Rasilla Álvarez, Domingo

    2016-04-01

    Most of the fire activity across Spain concentrates during the summer months, but a secondary peak appears also during late winter and early spring (February and March). This peak represents a tiny fraction of the burned surface but in northern Spain becomes the main fire season, representing up to 60 % of the total burned surface. Moreover, the impact of this "unseasonal" fire regime is becoming more relevant; an analysis of the temporal evolution of the burned surface since 2005 shows that the suppression efforts of summer forest fires have apparently succeeded, while the opposite has occurred with late winter-early spring forest fires. For example, during March 2012 more than 22,000 ha were burned in the Spanish provinces of Asturias and Cantabria, while about 14,000 suffers the effects of fires in Northern Portugal. Anthropogenic factor (mostly linked to an extensive cattle farming in the mountains) are the main cause of such fire activity, but atmospheric factors also play a relevant role in the spread of this fires. Consequently, the main aim of this poster is to explore if the recent evolution of forest fires in the study area are consequence of an aggravation of the atmospheric conditions driving to more fire risk conditions, or other factor could also explain the increase in fire activity. Burned surface data obtained from official statistics since 1971 were compared with atmospheric data at two temporal scales: daily fire risk values calculated from synoptic records and long term drought indices (SPI and SPEI). The results show a long term increase in both daily fire risk and drought conditions, but this trend can be related to the background warming of the area, rather to an increase in the frequency and magnitude of the extreme fire weather events. Thus, we consider that the regional atmospheric evolution cannot explain by itself the recent increase in late winter-early spring fire activity. Additional anthropogenic factors, such as recent changes in

  3. Activity of 3-Ketosteroid 9α-Hydroxylase (KshAB) Indicates Cholesterol Side Chain and Ring Degradation Occur Simultaneously in Mycobacterium tuberculosis*

    PubMed Central

    Capyk, Jenna K.; Casabon, Israël; Gruninger, Robert; Strynadka, Natalie C.; Eltis, Lindsay D.

    2011-01-01

    Mycobacterium tuberculosis (Mtb), a significant global pathogen, contains a cholesterol catabolic pathway. Although the precise role of cholesterol catabolism in Mtb remains unclear, the Rieske monooxygenase in this pathway, 3-ketosteroid 9α-hydroxylase (KshAB), has been identified as a virulence factor. To investigate the physiological substrate of KshAB, a rhodococcal acyl-CoA synthetase was used to produce the coenzyme A thioesters of two cholesterol derivatives: 3-oxo-23,24-bisnorchol-4-en-22-oic acid (forming 4-BNC-CoA) and 3-oxo-23,24-bisnorchola-1,4-dien-22-oic acid (forming 1,4-BNC-CoA). The apparent specificity constant (kcat/Km) of KshAB for the CoA thioester substrates was 20–30 times that for the corresponding 17-keto compounds previously proposed as physiological substrates. The apparent KmO2 was 90 ± 10 μm in the presence of 1,4-BNC-CoA, consistent with the value for two other cholesterol catabolic oxygenases. The Δ1 ketosteroid dehydrogenase KstD acted with KshAB to cleave steroid ring B with a specific activity eight times greater for a CoA thioester than the corresponding ketone. Finally, modeling 1,4-BNC-CoA into the KshA crystal structure suggested that the CoA moiety binds in a pocket at the mouth of the active site channel and could contribute to substrate specificity. These results indicate that the physiological substrates of KshAB are CoA thioester intermediates of cholesterol side chain degradation and that side chain and ring degradation occur concurrently in Mtb. This finding has implications for steroid metabolites potentially released by the pathogen during infection and for the design of inhibitors for cholesterol-degrading enzymes. The methodologies and rhodococcal enzymes used to generate thioesters will facilitate the further study of cholesterol catabolism. PMID:21987574

  4. Adrenergic activation of melatonin secretion in ovine pineal explants in short-term superfusion culture occurs via protein synthesis independent and dependent phenomena.

    PubMed

    Lewczuk, Bogdan; Ziółkowska, Natalia; Prusik, Magdalena; Przybylska-Gornowicz, Barbara

    2014-01-01

    The ovine pineal is generally considered as an interesting model for the study on adrenergic regulation of melatonin secretion due to some functional similarities with this gland in the human. The present investigations, performed in the superfusion culture of pineal explants, demonstrated that the norepinephrine-induced elevation of melatonin secretion in ovine pinealocytes comprised of two subsequent periods: a rapid increase phase and a slow increase phase. The first one included the quick rise in release of N-acetylserotonin and melatonin, occurring parallel to elevation of NE concentration in the medium surrounding explants. This rapid increase phase was not affected by inhibition of translation. The second, slow increase phase began after NE level had reached the maximum concentration in the culture medium and lasted about two hours. It was completely abolished by the treatment with translation inhibitors. The obtained results showed for the first time that the regulation of N-acetylserotonin synthesis in pinealocytes of some species like the sheep involves the on/off mechanism, which is completely independent of protein synthesis and works very fast. They provided strong evidence pointing to the need of revision of the current opinion that arylalkylamines N-acetyltransferase activity in pinealocytes is controlled exclusively by changes in enzyme abundance.

  5. Adrenergic Activation of Melatonin Secretion in Ovine Pineal Explants in Short-Term Superfusion Culture Occurs via Protein Synthesis Independent and Dependent Phenomena

    PubMed Central

    2014-01-01

    The ovine pineal is generally considered as an interesting model for the study on adrenergic regulation of melatonin secretion due to some functional similarities with this gland in the human. The present investigations, performed in the superfusion culture of pineal explants, demonstrated that the norepinephrine-induced elevation of melatonin secretion in ovine pinealocytes comprised of two subsequent periods: a rapid increase phase and a slow increase phase. The first one included the quick rise in release of N-acetylserotonin and melatonin, occurring parallel to elevation of NE concentration in the medium surrounding explants. This rapid increase phase was not affected by inhibition of translation. The second, slow increase phase began after NE level had reached the maximum concentration in the culture medium and lasted about two hours. It was completely abolished by the treatment with translation inhibitors. The obtained results showed for the first time that the regulation of N-acetylserotonin synthesis in pinealocytes of some species like the sheep involves the on/off mechanism, which is completely independent of protein synthesis and works very fast. They provided strong evidence pointing to the need of revision of the current opinion that arylalkylamines N-acetyltransferase activity in pinealocytes is controlled exclusively by changes in enzyme abundance. PMID:25133175

  6. Inhibition of the mutagenicity of bay-region diol epoxides of polycyclic aromatic hydrocarbons by naturally occurring plant phenols: Exceptional activity of ellagic acid

    PubMed Central

    Wood, Alexander W.; Huang, Mou-Tuan; Chang, Richard L.; Newmark, Harold L.; Lehr, Roland E.; Yagi, Haruhiko; Sayer, Jane M.; Jerina, Donald M.; Conney, Allan H.

    1982-01-01

    Ferulic, caffeic, chlorogenic, and ellagic acids, four naturally occurring plant phenols, inhibit the mutagenicity and cytotoxicity of (±)-7β,8α-dihydroxy-9α, 10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P 7,8-diol-9,10-epoxide-2), the only known ultimate carcinogenic metabolite of benzo[a]pyrene. The mutagenicity of 0.05 nmol of B[a]P 7,8-diol-9,10-epoxide-2 in strain TA100 of Salmonella typhimurium is inhibited 50% by incubation of the bacteria and the diol epoxide with 150 nmol of ferulic acid, 75 nmol of caffeic acid, 50 nmol of chlorogenic acid or, most strikingly, 1 nmol of ellagic acid in the 0.5-ml incubation mixture. A 3-nmol dose of ellagic acid inhibits mutation induction by 90%. Ellagic acid is also a potent antagonist of B[a]P 7,8-diol-9,10-epoxide-2 in Chinese hamster V79 cells. Mutations to 8-azaguanine resistance induced by 0.2 μM diol epoxide are reduced by 50% when tissue culture media also contains 2 μM ellagic acid. Similar to results obtained with the bacteria, ferulic, caffeic, and chlorogenic acids are approximately two orders of magnitude less active than ellagic acid in the mammalian cell assay. The antimutagenic effects of the plant phenols result from their direct interaction with B[a]P 7,8-diol-9,10-epoxide-2, because a concentration-dependent increase in the rate of diol epoxide disappearance in cell-free solutions of 1:9 dioxane/water, pH 7.0, is observed with all four phenols. In parallel with the mutagenicity studies, ellagic acid is 80-300 times more effective than the other phenols in accelerating the disappearance of B[a]P 7,8-diol-9,10-epoxide-2. Ellagic acid at 10 μM increases the disappearance of B[a]P 7,8-diol-9,10-epoxide-2 by approximately 20-fold relative to the spontaneous and hydronium ion-catalyzed hydrolysis of the diol epoxide at pH 7.0. Ellagic acid is a highly potent inhibitor of the mutagenic activity of bay-region diol epoxides of benzo[a]pyrene, dibenzo[a,h]pyrene, and dibenzo[a,i]pyrene, but higher

  7. Intramyocardial activation in early ventricular arrhythmias following coronary artery ligation.

    PubMed

    Kaplinsky, E; Ogawa, S; Kmetzo, J; Balke, C W; Dreifus, L S

    1980-01-01

    Subendocardial, subepicardial and intramyocardial activation in the ischemic zone was investigated in 20 anesthetized open chest dogs 0-30 minutes after the ligation of the left anterior descending coronary artery. Single and composite electrograms and lead 2 of the ECG were recorded. Coronary artery ligation produced marked delay, fragmentation, and reduction in amplitude in the electrical activity of the subepicardial and intramyocardial muscle layers. The activation remained synchronous in the subendocardial muscle layers. Extension of electrical activity in the ischemic subepicardium and intramyocardium beyond the T wave of the surface ECG preceded the onset of immediate ventricular arrhythmias (IVA) during the initial ten minute period after coronary artery ligation. However, a second surge of delayed ventricular arrhythmias (DVA), 10-30 minutes after ligation, was not associated with the appearance of diastolic electrical activity in any of the subepicardial or myocardial layers. It appears that subepicardial as well as intramyocardial reentry could play an important role in the genesis of the immediate ventricular arrhythmias (1-10 minutes after ligation). In contrast, no obvious reentrant activity as evidenced by delayed and fragmented electrical activity could be observed in the electrogram from any of the myocardial electrical activity could be observed in the electrogram from any of the myocardial layers with the appearance of delayed ventricular ectopic activity 10-30 minutes after ligation.

  8. Neutrophil priming occurs in a sequential manner and can be visualized in living animals by monitoring IL-1β promoter activation

    PubMed Central

    Yao, Yi; Matsushima, Hironori; Ohtola, Jennifer A.; Geng, Shuo; Lu, Ran; Takashima, Akira

    2014-01-01

    Rapid enhancement of phagocyte functionality is a hallmark of neutrophil priming. GeneChip analyses unveiled elevated CD54, dectin-2, and IL-1β mRNA expression by neutrophils isolated from inflammatory sites. In fact, CD54 and dectin-2 protein expression was detected on neutrophils recovered from skin, peritoneal and lung inflammation lesions, but not on those in bone marrow or peripheral blood. Neutrophils elevated CD54 and dectin-2 mRNA during migration in Boyden chambers and acquired CD54 and dectin-2 surface expression after subsequent exposure to GM-CSF. Neutrophils purified from IL-1β promoter-driven DsRed transgenic mice acquired DsRed signals during cell migration or exposure to GM-CSF. CD54 and dectin-2 were expressed by DsRed+ (but not DsRed–) neutrophils in GM-CSF-supplemented culture, and neutrophils recovered from inflammatory sites exhibited strong DsRed signals. The dynamic process of neutrophil priming was then studied in chemically induced inflammatory skin lesions by monitoring DsRed expression under confocal microscopy. A majority (>80%) of Ly6G+ neutrophils expressed DsRed, and those DsRed+/Ly6G+ cells exhibited crawling motion with a higher velocity compared to the DsRed–/Ly6G+ counterpart. This is the first report showing motile behaviors of primed neutrophils in living animals. We propose that neutrophil priming occurs in a sequential manner with rapid enhancement of phagocyte functionality followed by CD54 and dectin-2 mRNA and protein expression, IL-1β promoter activation, and accelerated motility. Not only do these findings provide a new conceptual framework for our understanding of the process of neutrophil priming, they also unveil new insights into the pathophysiology of many inflammatory disorders characterized by neutrophil infiltration. PMID:25527787

  9. Influence of load and stretch shortening cycle on the kinematics, kinetics and muscle activation that occurs during explosive upper-body movements.

    PubMed

    Newton, R U; Murphy, A J; Humphries, B J; Wilson, G J; Kraemer, W J; Häkkinen, K

    1997-01-01

    Although explosive power in lower-body movements has been extensively studied, there is a paucity of research examining such movements in the upper body. This study aimed to investigate the influence of load and the stretch shortening cycle (SSC) on the kinematics, kinetics, and muscle activation that occurs during maximal effort throws. A total of 17 male subjects performed SSC and concentric only (CO) bench throws using loads of 15%, 30%, 45%, 60%, 75%, 90% and 100% of their previously determined one repetition maximum bench press. The displacement, velocity, acceleration, force and power output as well as the electromyogram (EMG) from pectoralis major, anterior deltoid, and triceps brachii were recorded for each throw. The results were compared using multivariate analysis of variance with repeated measures. A criterion alpha level of P < or = 0.05 was used. Similar force velocity power relationships were determined for this multijoint upper-body movement as has been found for isolated muscles, single joint movements, and vertical jumping. The highest power output was produced at the 30% [563 (104) W] and 45% [560 (86) W] loads during the SSC throws. Force output increased as a function of load; however, even the lighter loads resulted in considerable force due to the high accelerations produced. Average velocity, average and peak force, and average and peak power output were significantly higher for the SSC throws compared to the CO throws. However, peak velocity and height thrown were not potentiated by performing the pre-stretch because the duration and range of movement allowed the ability of the muscle to generate force at high shortening velocities to dominate the resulting throw. As such, explosive movements involving longer concentric actions than experienced during brief SSC movements may be limited by the ability of the muscle to produce force during fast contraction velocities.

  10. Promoting Early Literacy Skills within Daily Activities and Routines in Preschool Classrooms

    ERIC Educational Resources Information Center

    Chandler, Lynette K.; Young, Robin Miller; Nylander, Donna; Shields, LuAnn; Ash, JoAnne; Bauman, Becky; Butts, Jill; Black, Kristine; Geraghty, Peggy; Hafer, Megan; Lay, Angie; Mitera, Brandie; Richardson, Debra; Steffen, Kara; Summers, Debra

    2008-01-01

    Many teachers and other service providers struggle with trying to address the many skills that are important for young children to acquire during the preschool years. Early Literacy Initiative project (Project ELI) is a comprehensive, two-tiered, early language and literacy intervention model that includes activities for all children as well as…

  11. Building Early Literacy and Language Skills: A Resource and Activity Guide for Preschool and Kindergarten.

    ERIC Educational Resources Information Center

    Paulson, Lucy Hart; Noble, Linda Attridge; Jepson, Stacia; van den Pol, Rick

    This book is a resource and activity guide for early childhood educators and care providers that helps to enhance the development of early and emerging literacy skills in young children. Its philosophy is based on the premise that both language and literacy development begin at birth and that educators and caretakers of young children have a…

  12. 78 FR 48863 - Agency Information Collection Activities; Comment Request; Evaluation of the Early Warning and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-12

    ... Agency Information Collection Activities; Comment Request; Evaluation of the Early Warning and Intervention Monitoring System AGENCY: Institute of Education Sciences/National Center for Education Statistics... Early Warning and Intervention Monitoring System. OMB Control Number: 1850-NEW. Type of Review: A...

  13. 78 FR 38957 - Agency Information Collection Activities; Comment Request; Race to the Top-Early Learning...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-28

    ... Agency Information Collection Activities; Comment Request; Race to the Top--Early Learning Challenge... Learning Challenge Annual Performance Report. OMB Control Number: 1810-NEW. Type of Review: A new... to the Top--Early Learning Challenge program is authorized by Sections 14005 and 14006, Division...

  14. Early High Tc Activity in Japan: The Franco Rasetti Lecture

    NASA Astrophysics Data System (ADS)

    Tanaka, Shoji

    2007-03-01

    From 1960 to 1980, R&D of superconductivity in Japan was carried out mainly to improve A15 superconducting wires and magnets. Improvement of wires were made mainly in the National Institute for Metals, and improvements of superconducting magnets were made in the Japan Atomic Energy Research Institute for future nuclear fusion reactors, the National Railway Laboratory for future maglev trains and also in the Electo-Technical Laboratory for MHD generators. I began the research of BPBO in 1975 and at that time the research of oxide superconductors was limited only to my laboratory in the University of Tokyo. During the study of this new superconductor, we learned quite a lot on how to make ceramic samples, how to measure electrical conductivity and magnetic susceptibility at low temperatures. In 1982, Prof. S. Nakajima organized a rather small group for investigating ``New Superconducting Phenomena,'' and I became a member of the group. In 1985, Nakajima expanded the research group to include more than 5 experimentalists and 5 theoreticians. The title of the research was ``New Superconducting Materials'' and the funds came from the Ministry of Education of Japan. In late October, 1986, we followed the first paper of Bednorz and Muller, and immediately found the material includes high temperature superconductor and reported it to the group meeting held in early November. In early December, we confirmed La2-xBaxCuO4 is the real high temperature superconductor, the critical temperature is 28K. I sent a copy of our paper to Prof. Beasley of California and asked to inform this fact to his colleagues. Asahi Shimbun, the biggest newspaper in Japan announced this in its science section, and then many people knew the high temperature superconductor had been discovered. Then many physicists and chemists rushed to this field very quickly and many kinds of materials were synthesized. In the Government, the Ministry of Education, the Ministry of International Trade and Industry

  15. Therapeutic inhibition of the early phase of complement activation.

    PubMed

    Roos, Anja; Ramwadhdoebé, Tamara H; Nauta, Alma J; Hack, C Erik; Daha, Mohamed R

    2002-09-01

    The complement system is a key component of innate immunity against invading pathogens. However, undesired activation of complement is involved in inflammation and associated tissue damage in a number of pathological conditions, such as ischemia/reperfusion injury, autoimmune diseases, and rejection of allo- and xenografts. During recent years, various therapeutically active complement inhibitors have been developed. In vivo studies using these inhibitors underscored the value of complement inhibition in the prevention of tissue damage. The currently available complement inhibitors mainly target the effector phase of the complement system that is common to all three activation pathways. Such a complete block of complement activation breaks the innate anti-microbial barrier, thereby increasing the risk for infection. Therefore, the development of potent complement inhibitors that interfere in the recognition phase of a specific complement activation pathway will generate important novel possibilities for treatment. The present review is focused on molecules that are able to inhibit the function of C1q and MBL, the recognition units of the classical pathway and the lectin pathway of complement, respectively. The potential value of these molecules for the development of therapeutically active complement inhibitors is discussed.

  16. Developing Constructivist Early Childhood Curriculum: Practical Principles and Activities. Early Childhood Education Series.

    ERIC Educational Resources Information Center

    DeVries, Rheta; Zan, Betty; Hildebrandt, Carolyn; Edmiaston, Rebecca; Sales, Christina

    This book provides a constructivist interpretation of developmentally appropriate preschool and kindergarten curriculum, incorporating descriptions of how activities are transformed over time and how children's reasoning is transformed, and placing the interpretation in the context of the play-oriented approach advocated by the National…

  17. Elevation of Alanine Aminotransferase Activity Occurs after Activation of the Cell-Death Signaling Initiated by Pattern-Recognition Receptors ‎but before Activation of Cytolytic Effectors in NK or CD8+ T Cells in the Liver During Acute HCV Infection

    PubMed Central

    Choi, Youkyung H.; Jin, Nancy; Kelly, Fiona; Sakthivel, SenthilKumar K.; Yu, Tianwei

    2016-01-01

    Pattern-recognition receptors (PRRs) promote host defenses against HCV infection by binding to their corresponding adapter molecules leading to the initiation of innate immune responses including cell death. We investigated the expression of PRR genes, biomarkers of liver cell-death, and T cell and NK cell activation/inhibition-related genes in liver and serum obtained from three experimentally infected chimpanzees with acute HCV infection, and analyzed the correlation between gene expression levels and clinical profiles. Our results showed that expression of hepatic RIG-I, TLR3, TLR7, 2OAS1, and CXCL10 mRNAs was upregulated as early as 7 days post-inoculation and peaked 12 to 83 days post-inoculation. All of the three HCV infected chimpanzees exhibited significant elevations of serum alanine aminotransferase (ALT) activity between 70 and 95 days after inoculation. Elevated levels of serum cytokeratin 18 (CK-18) and caspases 3 and 7 activity coincided closely with the rise of ALT activity, and were preceded by significant increases in levels of caspase 3 and caspase 7 mRNAs in the liver. Particularly we found that significant positive auto-correlations were observed between RIG-I, TLR3, CXCL10, 2OAS1, and PD-L1 mRNA and ALT activity at 3 to 12 days before the peak of ALT activity. However, we observed substantial negative auto-correlations between T cell and NK cell activation/inhibition-related genes and ALT activity at 5 to 32 days after the peak of ALT activity. Our results indicated cell death signaling is preceded by early induction of RIG-I, TLR3, 2OAS1, and CXCL10 mRNAs which leads to elevation of ALT activity and this signaling pathway occurs before the activation of NK and T cells during acute HCV infection. Our study suggests that PRRs and type I IFN response may play a critical role in development of liver cell injury related to viral clearance during acute HCV infection. PMID:27788241

  18. Trajectories of Risk for Early Sexual Activity and Early Substance Use in the Fast Track Prevention Program

    PubMed Central

    2013-01-01

    Children who exhibit early-starting conduct problems are more likely than their peers to initiate sexual activity and substance use at an early age, experience pregnancy, and contract a sexually-transmitted disease [STD], placing them at risk for HIV/AIDS. Hence, understanding the development of multi-problem profiles among youth with early-starting conduct problems may benefit the design of prevention programs. In this study, 1,199 kindergarten children (51 % African American; 47 % European American; 69 % boys) over-sampled for high rates of aggressive-disruptive behavior problems were followed through age 18. Latent class analyses (LCA) were used to define developmental profiles associated with the timing of initiation of sexual activity, tobacco and alcohol/drug use and indicators of risky adolescent sex (e.g. pregnancy and STD). Half of the high-risk children were randomized to a multi-component preventive intervention (Fast Track). The intervention did not significantly reduce membership in the classes characterized by risky sex practices. However, additional analyses examined predictors of poor outcomes, which may inform future prevention efforts. PMID:23417666

  19. Scissor Sorcery: Cutting Activities for the Early Childhood Curriculum.

    ERIC Educational Resources Information Center

    Carpenter, Sharan Bryant

    This handbook, designed for use with preschool and elementary age children, provides instructions and instructional materials for the development of proficiency in cutting. Scissor cutting is a critically important activity for young children to practice because, along with coloring and pasting, it is used widely to foster the three R's as well as…

  20. Alteration of mTOR signaling occurs early in the progression of Alzheimer disease (AD): analysis of brain from subjects with pre-clinical AD, amnestic mild cognitive impairment and late-stage AD.

    PubMed

    Tramutola, Antonella; Triplett, Judy C; Di Domenico, Fabio; Niedowicz, Dana M; Murphy, Michael P; Coccia, Raffaella; Perluigi, Marzia; Butterfield, D Allan

    2015-06-01

    The clinical symptoms of Alzheimer disease (AD) include a gradual memory loss and subsequent dementia, and neuropathological deposition of senile plaques and neurofibrillary tangles. At the molecular level, AD subjects present overt amyloid β (Aβ) production and tau hyperphosphorylation. Aβ species have been proposed to overactivate the phosphoinositide3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) axis, which plays a central role in proteostasis. The current study investigated the status of the PI3K/Akt/mTOR pathway in post-mortem tissue from the inferior parietal lobule (IPL) at three different stages of AD: late AD, amnestic mild cognitive impairment (MCI) and pre-clinical AD (PCAD). Our findings suggest that the alteration of mTOR signaling and autophagy occurs at early stages of AD. We found a significant increase in Aβ (1-42) levels, associated with reduction in autophagy (Beclin-1 and LC-3) observed in PCAD, MCI, and AD subjects. Related to the autophagy impairment, we found a hyperactivation of PI3K/Akt/mTOR pathway in IPL of MCI and AD subjects, but not in PCAD, along with a significant decrease in phosphatase and tensin homolog. An increase in two mTOR downstream targets, p70S6K and 4EBP1, occurred in AD and MCI subjects. Both AD and MCI subjects showed increased, insulin receptor substrate 1, a candidate biomarker of brain insulin resistance, and GSK-3β, a kinase targeting tau phosphorylation. Nevertheless, tau phosphorylation was increased in the clinical groups. The results hint at a link between Aβ and the PI3K/Akt/mTOR axis and provide further insights into the relationship between AD pathology and insulin resistance. In addition, we speculate that the alteration of mTOR signaling in the IPL of AD and MCI subjects, but not in PCAD, is due to the lack of substantial increase in oxidative stress. The figure represents the three different stages of Alzheimer Disease: Preclinical Alzheimer Disease (PCAD), Mild cognitive impairment (MCI

  1. Exposure to mercury alters early activation events in fish leukocytes.

    PubMed Central

    MacDougal, K C; Johnson, M D; Burnett, K G

    1996-01-01

    Although fish in natural populations may carry high body burdens of both organic and inorganic mercury, the effects of this divalent metal on such lower vertebrates is poorly understood. In this report, inorganic mercury in the form of mercuric chloride (HgCl2) is shown to produce both high-dose inhibition and low-dose activation of leukocytes in a marine teleost fish, Sciaenops ocellatus. Concentrations of inorganic mercury > or = 10 microM suppressed DNA synthesis and induced rapid influx of radiolabeled calcium, as well as tyrosine phosphorylation of numerous cellular proteins. Lower concentrations (0.1-1 microM) of HgCl2 that activated cell growth also induced a slow sustained rise in intracellular calcium in cells loaded with the calcium indicator dye fura-2, but did not produce detectable tyrosine phosphorylation of leukocyte proteins. These studies support the possibility that subtoxic doses of HgCl2 may inappropriately activate teleost leukocytes, potentially altering the processes that regulate the magnitude and specificity of the fish immune response to environmental pathogens. Images Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. Figure 7. PMID:8930553

  2. Early death in active professional athletes: Trends and causes.

    PubMed

    Lemez, S; Wattie, N; Baker, J

    2016-05-01

    The objective of the study was to examine mortality trends and causes of death among professional athletes from the four major sports in North America who died during their playing careers. 205 deceased athletes who were registered as active when they died from the National Basketball Association (NBA), National Football League (NFL), National Hockey League (NHL), and Major League Baseball (MLB) were examined. Results were compared with the Canadian and U.S. general population. The leading causes of death in players reflected the leading causes of death in the Canadian and U.S. general population (i.e., car accidents). Descriptively, NFL and NBA players had a higher likelihood of dying in a car accident (OR 1.75, 95% CI: 0.91-3.36) compared with NHL and MLB players. In addition, NFL and NBA players had a significantly higher likelihood of dying from a cardiac-related illness (OR 4.44, 95% CI: 1.59-12.43). Mortality trends were disproportionate to team size. Overall, death in active athletes is low. Out of 53 400 athletes who have historically played in the four leagues, only 205 died while active (0.38%). Future examinations into the trends and causes of mortality in elite athlete populations will create a better understanding of health-related risks in elite sport.

  3. Early aqueous activity on primitive meteorite parent bodies.

    PubMed

    Endress, M; Zinner, E; Bischoff, A

    1996-02-22

    The interstellar material from which the solar system formed has been modified by many processes: evaporation and condensation in the solar nebula, accretion into protoplanetary bodies and post-accretion processes within these bodies. Meteorites provide a record of these events and their chronology. Carbonaceous CI chondrites are among the most primitive, undifferentiated meteorites, but nevertheless show evidence of post-accretion alteration; they contain carbonates that are believed to have formed by reactions between anhydrous CI precursor materials and circulating fluids in the meteorite parent body (or bodies), yet little is known about the nature of these reactions or the timescale on which they occurred. Here we report measurements of excess 53Cr--formed by the decay of short-lived 53Mn--in five carbonate fragments from the CI chondrites Orgueil and Ivuna. Our results show that aqueous alteration on small protoplanetary bodies must have begun less than 20 Myr after the time of formation of the oldest known solar-nebula condensates (Allende refractory inclusions). This upper limit is much shorter than that of 50 Myr inferred from previous studies, and clearly establishes aqueous alteration as one of the earliest processes in the chemical evolution of the solar system.

  4. The use of early summer mosquito surveillance to predict late summer West Nile virus activity

    USGS Publications Warehouse

    Ginsberg, Howard S.; Rochlin, Ilia; Campbell, Scott R.

    2010-01-01

    Utility of early-season mosquito surveillance to predict West Nile virus activity in late summer was assessed in Suffolk County, NY. Dry ice-baited CDC miniature light traps paired with gravid traps were set weekly. Maximum-likelihood estimates of WNV positivity, minimum infection rates, and % positive pools were generally well correlated. However, positivity in gravid traps was not correlated with positivity in CDC light traps. The best early-season predictors of WNV activity in late summer (estimated using maximum-likelihood estimates of Culex positivity in August and September) were early date of first positive pool, low numbers of mosquitoes in July, and low numbers of mosquito species in July. These results suggest that early-season entomological samples can be used to predict WNV activity later in the summer, when most human cases are acquired. Additional research is needed to establish which surveillance variables are most predictive and to characterize the reliability of the predictions.

  5. Oocyte-expressed yes-associated protein is a key activator of the early zygotic genome in mouse

    PubMed Central

    Yu, Chao; Ji, Shu-Yan; Dang, Yu-Jiao; Sha, Qian-Qian; Yuan, Yi-Feng; Zhou, Jian-Jie; Yan, Li-Ying; Qiao, Jie; Tang, Fuchou; Fan, Heng-Yu

    2016-01-01

    In early mammalian embryos, the genome is transcriptionally quiescent until the zygotic genome activation (ZGA) which occurs 2-3 days after fertilization. Despite a long-standing effort, maternal transcription factors regulating this crucial developmental event remain largely elusive. Here, using maternal and paternal mouse models of Yap1 deletion, we show that maternally accumulated yes-associated protein (YAP) in oocyte is essential for ZGA. Maternal Yap1-knockout embryos exhibit a prolonged two-cell stage and develop into the four-cell stage at a much slower pace than the wild-type controls. Transcriptome analyses identify YAP target genes in early blastomeres; two of which, Rpl13 and Rrm2, are required to mediate maternal YAP's effect in conferring developmental competence on preimplantation embryos. Furthermore, the physiological YAP activator, lysophosphatidic acid, can substantially improve early development of wild-type, but not maternal Yap1-knockout embryos in both oviduct and culture. These observations provide insights into the mechanisms of ZGA, and suggest potentials of YAP activators in improving the developmental competence of cultured embryos in assisted human reproduction and animal biotechnology. PMID:26902285

  6. Oocyte-expressed yes-associated protein is a key activator of the early zygotic genome in mouse.

    PubMed

    Yu, Chao; Ji, Shu-Yan; Dang, Yu-Jiao; Sha, Qian-Qian; Yuan, Yi-Feng; Zhou, Jian-Jie; Yan, Li-Ying; Qiao, Jie; Tang, Fuchou; Fan, Heng-Yu

    2016-03-01

    In early mammalian embryos, the genome is transcriptionally quiescent until the zygotic genome activation (ZGA) which occurs 2-3 days after fertilization. Despite a long-standing effort, maternal transcription factors regulating this crucial developmental event remain largely elusive. Here, using maternal and paternal mouse models of Yap1 deletion, we show that maternally accumulated yes-associated protein (YAP) in oocyte is essential for ZGA. Maternal Yap1-knockout embryos exhibit a prolonged two-cell stage and develop into the four-cell stage at a much slower pace than the wild-type controls. Transcriptome analyses identify YAP target genes in early blastomeres; two of which, Rpl13 and Rrm2, are required to mediate maternal YAP's effect in conferring developmental competence on preimplantation embryos. Furthermore, the physiological YAP activator, lysophosphatidic acid, can substantially improve early development of wild-type, but not maternal Yap1-knockout embryos in both oviduct and culture. These observations provide insights into the mechanisms of ZGA, and suggest potentials of YAP activators in improving the developmental competence of cultured embryos in assisted human reproduction and animal biotechnology.

  7. SECONDARY WASTE MANAGEMENT FOR HANFORD EARLY LOW ACTIVITY WASTE VITRIFICATION

    SciTech Connect

    UNTERREINER BJ

    2008-07-18

    More than 200 million liters (53 million gallons) of highly radioactive and hazardous waste is stored at the U.S. Department of Energy's Hanford Site in southeastern Washington State. The DOE's Hanford Site River Protection Project (RPP) mission includes tank waste retrieval, waste treatment, waste disposal, and tank farms closure activities. This mission will largely be accomplished by the construction and operation of three large treatment facilities at the Waste Treatment and Immobilization Plant (WTP): (1) a Pretreatment (PT) facility intended to separate the tank waste into High Level Waste (HLW) and Low Activity Waste (LAW); (2) a HLW vitrification facility intended to immobilize the HLW for disposal at a geologic repository in Yucca Mountain; and (3) a LAW vitrification facility intended to immobilize the LAW for shallow land burial at Hanford's Integrated Disposal Facility (IDF). The LAW facility is on target to be completed in 2014, five years prior to the completion of the rest of the WTP. In order to gain experience in the operation of the LAW vitrification facility, accelerate retrieval from single-shell tank (SST) farms, and hasten the completion of the LAW immobilization, it has been proposed to begin treatment of the low-activity waste five years before the conclusion of the WTP's construction. A challenge with this strategy is that the stream containing the LAW vitrification facility off-gas treatment condensates will not have the option of recycling back to pretreatment, and will instead be treated by the Hanford Effluent Treatment Facility (ETF). Here the off-gas condensates will be immobilized into a secondary waste form; ETF solid waste.

  8. Early and current physical activity: relationship with intima-media thickness and metabolic variables in adulthood

    PubMed Central

    Lima, Manoel C. S.; Barbosa, Maurício F.; Diniz, Tiego A.; Codogno, Jamile S.; Freitas, Ismael F.; Fernandes, Rômulo A.

    2014-01-01

    Background: It is unclear whether early physical activity has a greater influence on intima-media thickness and metabolic variables than current physical activity. Objective: To analyze the relationship between current and early physical activity, metabolic variables, and intima-media thickness measures in adults. Method: The sample was composed of 55 healthy subjects of both sexes (33 men and 22 women). Total body fat and trunk fat were estimated by dual-energy X-ray absorptiometry. Carotid and femoral intima-media thickness were measured using a Doppler ultrasound device. A 12-hour fasting blood sample collection was taken (fasting glucose and lipid profile). Early physical activity was assessed through face-to-face interview, and the current physical activity was assessed by pedometer (Digi-Walker Yamax, SW200), which was used for a period of seven days. Results: Current physical activity was negatively related to total cholesterol (rho=-0.31), while early physical activity was negatively related to triglycerides (rho=-0.42), total cholesterol (rho=-0.28), very low density lipoprotein (rho=-0.44), and carotid intima-media thickness (rho=-0.50). In the multivariate model, subjects engaged in sports activities during early life had lower values of very low density lipoprotein (b=-8.74 [b=-16.1; -1.47]) and carotid intima-media thickness (b=-0.17 [95%CI: -0.28; -0.05]). Conclusion: Early 95%CI physical activity has a significant influence on carotid intima-media thickness, regardless of the current physical activity. PMID:25372009

  9. Identification of GATA2 and AP-1 activator elements within the enhancer VNTR occurring in intron 5 of the human SIRT3 gene

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Human SIRT3 gene contains an intronic VNTR enhancer. A T > C transition occurring in the second repeat of each VNTR allele implies the presence/absence of a putative GATA binding motif. A partially overlapping AP-1 site, not affected by the transition, was also identified. Aims of the present study ...

  10. Early Site Permit Demonstration Program: Recommendations for communication activities and public participation in the Early Site Permit Demonstration Program

    SciTech Connect

    Not Available

    1993-01-27

    On October 24, 1992, President Bush signed into law the National Energy Policy Act of 1992. The bill is a sweeping, comprehensive overhaul of the Nation`s energy laws, the first in more than a decade. Among other provisions, the National Energy Policy Act reforms the licensing process for new nuclear power plants by adopting a new approach developed by the US Nuclear Regulatory Commission (NRC) in 1989, and upheld in court in 1992. The NRC 10 CFR Part 52 rule is a three-step process that guarantees public participation at each step. The steps are: early site permit approval; standard design certifications; and, combined construction/operating licenses for nuclear power reactors. Licensing reform increases an organization`s ability to respond to future baseload electricity generation needs with less financial risk for ratepayers and the organization. Costly delays can be avoided because design, safety and siting issues will be resolved before a company starts to build a plant. Specifically, early site permit approval allows for site suitability and acceptability issues to be addressed prior to an organization`s commitment to build a plant. Responsibility for site-specific activities, including communications and public participation, rests with those organizations selected to try out early site approval. This plan has been prepared to assist those companies (referred to as sponsoring organizations) in planning their communications and public involvement programs. It provides research findings, information and recommendations to be used by organizations as a resource and starting point in developing their own plans.

  11. Initiation of ART during Early Acute HIV Infection Preserves Mucosal Th17 Function and Reverses HIV-Related Immune Activation

    PubMed Central

    Schuetz, Alexandra; Deleage, Claire; Sereti, Irini; Rerknimitr, Rungsun; Phanuphak, Nittaya; Phuang-Ngern, Yuwadee; Estes, Jacob D.; Sandler, Netanya G.; Sukhumvittaya, Suchada; Marovich, Mary; Jongrakthaitae, Surat; Akapirat, Siriwat; Fletscher, James L. K.; Kroon, Eugene; Dewar, Robin; Trichavaroj, Rapee; Chomchey, Nitiya; Douek, Daniel C.; O′Connell, Robert J.; Ngauy, Viseth; Robb, Merlin L.; Phanuphak, Praphan; Michael, Nelson L.; Excler, Jean-Louis; Kim, Jerome H.; de Souza, Mark S.; Ananworanich, Jintanat

    2014-01-01

    Mucosal Th17 cells play an important role in maintaining gut epithelium integrity and thus prevent microbial translocation. Chronic HIV infection is characterized by mucosal Th17 cell depletion, microbial translocation and subsequent immune-activation, which remain elevated despite antiretroviral therapy (ART) correlating with increased mortality. However, when Th17 depletion occurs following HIV infection is unknown. We analyzed mucosal Th17 cells in 42 acute HIV infection (AHI) subjects (Fiebig (F) stage I-V) with a median duration of infection of 16 days and the short-term impact of early initiation of ART. Th17 cells were defined as IL-17+ CD4+ T cells and their function was assessed by the co-expression of IL-22, IL-2 and IFNγ. While intact during FI/II, depletion of mucosal Th17 cell numbers and function was observed during FIII correlating with local and systemic markers of immune-activation. ART initiated at FI/II prevented loss of Th17 cell numbers and function, while initiation at FIII restored Th17 cell numbers but not their polyfunctionality. Furthermore, early initiation of ART in FI/II fully reversed the initially observed mucosal and systemic immune-activation. In contrast, patients treated later during AHI maintained elevated mucosal and systemic CD8+ T-cell activation post initiation of ART. These data support a loss of Th17 cells at early stages of acute HIV infection, and highlight that studies of ART initiation during early AHI should be further explored to assess the underlying mechanism of mucosal Th17 function preservation. PMID:25503054

  12. Cholecystitis occurring without stones

    SciTech Connect

    Seal, M.L.

    1986-03-01

    A case of acalculous cholecystitis in a 65-year-old man with underlying diabetes mellitus, hypertension, and peripheral arteriosclerosis is presented here. His case remained diagnostically puzzling for some time until symptoms and signs became more severe and very suggestive of acute cholecystitis. The clinical impression was then supported by an abnormal radioisotope biliary scan. The scan has fairly good sensitivity in detecting this condition but may not be totally dependable. Acalculous cholecystitis is an unusual but serious variant of a common disorder in which treatable gallbladder disease may masquerade as a less treatable liver malady. A common denominator among this disorder's many etiologies may be impairment of the gallbladder microcirculation in the presence of one or more conditions that lower the gallbladder's resistance to bacterial invasion. Prompt detection and treatment are desirable to reduce morbidity and mortality. However, early diagnosis is not always possible, because the clinical picture often is unclear, clear, gallstones are absent, and laboratory test results may be normal or equivocal. As in the case reported here, the vague clinical picture may dictate following a patient until the illness reaches an intensity acute enough to permit identification. The greatest aid to earlier diagnosis for the physician faced with circumstances similar to those described here is to think of cholecystitis and then to give strong weight to that clinical suspicion. At times, a recommendation for cholecystectomy may have to be made mainly on clinical judgment.

  13. Fluvial deposits as an archive of early human activity

    NASA Astrophysics Data System (ADS)

    Mishra, S.; White, M. J.; Beaumont, P.; Antoine, P.; Bridgland, D. R.; Limondin-Lozouet, N.; Santisteban, J. I.; Schreve, D. C.; Shaw, A. D.; Wenban-Smith, F. F.; Westaway, R. W. C.; White, T. S.

    2007-11-01

    River terraces are well established as an important source of Lower and Middle Palaeolithic artefacts in Europe, large collections having been assembled there during the years of manual gravel extraction. Now that many terrace sequences can be reliably dated and correlated with the oceanic record, potentially useful patterns can be recognized in the distribution of artefacts. The earliest appearance of artefacts in terrace staircases, marking the arrival of the first tool-making hominins in the region in question, is the first of several archaeological markers within fluvial sequences. The Lower to Middle Palaeolithic transition, with the appearance of Levallois, is another. Others may be more regional in significance: the occurrences of Clactonian (Mode 1) industry, twisted ovate handaxes and bout coupé handaxes, for example. IGCP Project no. 449 instigated the compilation of fluvial records from all over the 'old world'. Comparison between British and Central European sequences confirms the established view that there is a demarcation between handaxe making in the west and flake/core industries in the east. Other centres of activity reported here have been in the Middle East (Syria), South Africa and India. Data from such areas will be key in deciphering the story of the earlier 'out-of-Africa' migration, that by pre-Homo sapiens people. There is clear evidence for diachroneity between the first appearances of different industries, in keeping with the well-established idea of northward migration.

  14. Physical Activity, Self-Regulation, and Early Academic Achievement in Preschool Children

    ERIC Educational Resources Information Center

    Becker, Derek R.; McClelland, Megan M.; Loprinzi, Paul; Trost, Stewart G.

    2014-01-01

    Research Findings: The present study investigated whether active play during recess was associated with self-regulation and academic achievement in a prekindergarten sample. A total of 51 children in classes containing approximately half Head Start children were assessed on self-regulation, active play, and early academic achievement. Path…

  15. The Child as an Active Learner: Views, Practices, and Barriers in Chinese Early Childhood Education

    ERIC Educational Resources Information Center

    Tang, Fengling

    2006-01-01

    The Chinese view of the child is in the process of changing from the dependent child of traditional Chinese society to the child as an active learner in contemporary China. The view of the child as an active learner forces early childhood practitioners to rethink the features of the child's learning and development, individuality, and needs and…

  16. Embedding Physical Activity and Nutrition in Early Care and Education Programs

    ERIC Educational Resources Information Center

    Deiner, Penny Low; Qiu, Wei

    2007-01-01

    The infant and toddler years provide a window of opportunity to establish healthy habits as part of daily routines and activities that prevent childhood obesity. Early care and education programs have the opportunity to make a significant impact on physical development when they promote healthy eating and physical activity in their daily routines.…

  17. Children's Collective Activities and Peer Culture in Early Literacy in American and Italian Preschools.

    ERIC Educational Resources Information Center

    Corsaro, William A.; Nelson, Elizabeth

    2003-01-01

    Examines American and Italian children's early literacy awareness and activities in preschools. Reveals that children take literacy activities and knowledge from formal lessons and then use, refine, and extend these activites with peers. Considers implications of these findings for theoretical work on children's peer cultures and development of…

  18. Pilot-Testing CATCH Early Childhood: A Preschool-Based Healthy Nutrition and Physical Activity Program

    ERIC Educational Resources Information Center

    Sharma, Shreela; Chuang, Ru-Jye; Hedberg, Ann Marie

    2011-01-01

    Background: The literature on theoretically-based programs targeting healthy nutrition and physical activity in preschools is scarce. Purpose: To pilot test CATCH Early Childhood (CEC), a preschool-based nutrition and physical activity program among children ages three to five in Head Start. Methods: The study was conducted in two Head Start…

  19. Rainstorm Activities for Early Childhood Music Lessons Inspired by Teachable Moments

    ERIC Educational Resources Information Center

    Poole, Harrison Grant

    2016-01-01

    Activities that focus on already familiar concepts are good starting points when designing early childhood music lessons. The author uses teachable moments, a spider in the classroom and a rainstorm, to design interdisciplinary preschool group activities that teach music, math, and science concepts. Dynamics and tempo are the music concepts that…

  20. Out-of-School Literacy Activities of Affluent Early Adolescents: Selective Competencies and Hidden Needs

    ERIC Educational Resources Information Center

    Hester, Amy

    2012-01-01

    Few studies have documented the literacy activities in an after-school setting of affluent early adolescents assigned to remedial reading. This may be because these students are not considered to be at risk of academic failure. The out-of-school literacy activities of 3 sixth-grade students were examined in this qualitative research. Multiple data…

  1. Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions.

    PubMed Central

    Napoli, C; D'Armiento, F P; Mancini, F P; Postiglione, A; Witztum, J L; Palumbo, G; Palinski, W

    1997-01-01

    To determine whether oxidized LDL enhances atherogenesis by promoting monocyte recruitment into the vascular intima, we investigated whether LDL accumulation and oxidation precede intimal accumulation of monocytes in human fetal aortas (from spontaneous abortions and premature newborns who died within 12 h; fetal age 6.2+/-1.3 mo). For this purpose, a systematic assessment of fatty streak formation was carried out in fetal aortas from normocholesterolemic mothers (n = 22), hypercholesterolemic mothers (n = 33), and mothers who were hypercholesterolemic only during pregnancy (n = 27). Fetal plasma cholesterol levels showed a strong inverse correlation with fetal age (R = -0.88, P < 0.0001). In fetuses younger than 6 mo, fetal plasma cholesterol levels correlated with maternal ones (R = 0.86, P = 0.001), whereas in older fetuses no such correlation existed. Fetal aortas from hypercholesterolemic mothers and mothers with temporary hypercholesterolemia contained significantly more and larger lesions (758,651+/-87,449 and 451,255+/-37,448 micron2 per section, respectively; mean+/-SD) than aortas from normocholesterolemic mothers (61,862+/-9,555 micron2; P < 0.00005). Serial sections of the arch, thoracic, and abdominal aortas were immunostained for recognized markers of atherosclerosis: macrophages, apo B, and two different oxidation-specific epitopes (malondialdehyde- and 4-hydroxynonenal-lysine). Of the atherogenic sites that showed positive immunostaining for at least one of these markers, 58.6% were established lesions containing both macrophage/foam cells and oxidized LDL (OxLDL). 17.3% of all sites contained only native LDL, and 13.3% contained only OxLDL without monocyte/ macrophages. In contrast, only 4.3% of sites contained isolated monocytes in the absence of native or oxidized LDL. In addition, 6.3% of sites contained LDL and macrophages but few oxidation-specific epitopes. These results demonstrate that LDL oxidation and formation of fatty streaks occurs

  2. Naturally Occurring Food Toxins

    PubMed Central

    Dolan, Laurie C.; Matulka, Ray A.; Burdock, George A.

    2010-01-01

    Although many foods contain toxins as a naturally-occurring constituent or, are formed as the result of handling or processing, the incidence of adverse reactions to food is relatively low. The low incidence of adverse effects is the result of some pragmatic solutions by the US Food and Drug Administration (FDA) and other regulatory agencies through the creative use of specifications, action levels, tolerances, warning labels and prohibitions. Manufacturers have also played a role by setting limits on certain substances and developing mitigation procedures for process-induced toxins. Regardless of measures taken by regulators and food producers to protect consumers from natural food toxins, consumption of small levels of these materials is unavoidable. Although the risk for toxicity due to consumption of food toxins is fairly low, there is always the possibility of toxicity due to contamination, overconsumption, allergy or an unpredictable idiosyncratic response. The purpose of this review is to provide a toxicological and regulatory overview of some of the toxins present in some commonly consumed foods, and where possible, discuss the steps that have been taken to reduce consumer exposure, many of which are possible because of the unique process of food regulation in the United States. PMID:22069686

  3. Biomarkers of endothelial cell activation in early sepsis

    PubMed Central

    Skibsted, Simon; Jones, Alan E; Puskarich, Michael A.; Arnold, Ryan; Sherwin, Robert; Trzeciak, Stephen; Schuetz, Philipp; Aird, William C.; Shapiro, Nathan I

    2013-01-01

    PURPOSE To investigate the association of endothelial-related markers with organ dysfunction and in-hospital mortality to validate our earlier findings in a multicenter study. We hypothesize that: 1) endothelial biomarkers will be associated with organ dysfunction and mortality in sepsis; and, that sFlt-1, holds promise as novel prognostic markers in sepsis. METHODS A prospective, multicenter, observational study of a convenience sample of Emergency Department (ED) patients with a suspected infection presenting to one of four urban, academic medical center EDs between January 2009 and January 2010. We collected plasma while the patients were in the ED, and subsequently assayed endothelial-related biomarkers, namely sFlt-1, sE-Selectin, sICAM-1, sVCAM-1, and PAI-1. Outcomes were organ dysfunction and in-hospital mortality. RESULTS We enrolled at a total of 166 patients: 63 with sepsis (38%), 61 with severe sepsis (37%) and 42 with septic shock (25%). All endothelial biomarkers were significantly associated with sepsis severity, P < 0.002. We found a significant inter-correlation between all biomarkers, strongest between sFlt1 and PAI-1 (r=0.61, P < 0.001) and PAI-1 and sE-selectin and sICAM-1 (r=0.49, P < 0.001). Among the endothelial biomarkers, sFlt-1 had the strongest association with SOFA score (r=0.58, P < 0.001). sFlt-1 and PAI-1 had the highest area under the operating receiver characteristic curve for mortality of 0.87. CONCLUSIONS This multi-center validation study confirms that markers of endothelial activation are associated with sepsis severity, organ dysfunction and mortality in sepsis. This supports the hypothesis that the endothelium plays a central role in the pathophysiology of sepsis and may serve as a more accurate prediction tool and a target for therapies aimed at ameliorating endothelial cell dysfunction. Additionally, sFLT-1 holds promise as a novel sepsis severity biomarker. PMID:23524845

  4. Gypenoside XLIX, a naturally occurring gynosaponin, PPAR-alpha dependently inhibits LPS-induced tissue factor expression and activity in human THP-1 monocytic cells

    SciTech Connect

    Huang, Tom Hsun-Wei; Van Hoan Tran; Roufogalis, Basil D.; Li Yuhao . E-mail: yuhao@pharm.usyd.edu.au

    2007-01-01

    Tissue factor (TF) is involved not only in the progression of atherosclerosis and other cardiovascular diseases, but is also associated with tumor growth, metastasis, and angiogenesis and hence may be an attractive target for directed cancer therapeutics. Gynostemma pentaphyllum (GP) is widely used in the treatment of various cardiovascular diseases including atherosclerosis, as well as cancers. Gypenoside (Gyp) XLIX, a dammarane-type glycoside, is one of the prominent components in GP. We have recently reported Gyp XLIX to be a potent peroxisome proliferator-activated receptor (PPAR)-alpha activator. Here we demonstrate that Gyp XLIX (0-300 {mu}M) concentration dependently inhibited TF promoter activity after induction by the inflammatory stimulus lipopolysaccharide (LPS) in human monocytic THP-1 cells transfected with promoter reporter constructs pTF-LUC. Furthermore, Gyp XLIX inhibited LPS-induced TF mRNA and protein overexpression in THP-1 monocyte cells. Its inhibition of LPS-induced TF hyperactivity was further confirmed by chromogenic enzyme activity assay. The activities of Gyp XLIX reported in this study were similar to those of Wy-14643, a potent synthetic PPAR-alpha activator. Furthermore, the Gyp XLIX-induced inhibitory effect on TF luciferase activity was completely abolished in the presence of the PPAR-alpha selective antagonist MK-886. The present findings suggest that Gyp XLIX inhibits LPS-induced TF overexpression and enhancement of its activity in human THP-1 monocytic cells via PPAR-alpha-dependent pathways. The data provide new insights into the basis of the use of the traditional Chinese herbal medicine G. pentaphyllum for the treatment of cardiovascular and inflammatory diseases, as well as cancers.

  5. Retinoic acid inhibits induction of c-Jun protein by ultraviolet radiation that occurs subsequent to activation of mitogen-activated protein kinase pathways in human skin in vivo.

    PubMed

    Fisher, G J; Talwar, H S; Lin, J; Lin, P; McPhillips, F; Wang, Z; Li, X; Wan, Y; Kang, S; Voorhees, J J

    1998-03-15

    Human skin is exposed daily to solar ultraviolet (UV) radiation. UV induces the matrix metalloproteinases collagenase, 92-kD gelatinase, and stromelysin, which degrade skin connective tissue and may contribute to premature skin aging (photoaging). Pretreatment of skin with all-trans retinoic acid (tRA) inhibits UV induction of matrix metalloproteinases. We investigated upstream signal transduction pathways and the mechanism of tRA inhibition of UV induction of matrix metalloproteinases in human skin in vivo. Exposure of human skin in vivo to low doses of UV activated EGF receptors, the GTP-binding regulatory protein p21Ras, and stimulated mitogen-activated protein (MAP) kinases, extracellular signal-regulated kinase (ERK), c-Jun amino-terminal kinase (JNK), and p38. Both JNK and p38 phosphorylated, and thereby activated transcription factors c-Jun and activating transcription factor 2 (ATF-2), which bound to the c-Jun promoter and upregulated c-Jun gene expression. Elevated c-Jun, in association with constitutively expressed c-Fos, formed increased levels of transcription factor activator protein (AP) 1, which is required for transcription of matrix metalloproteinases. Pretreatment of human skin with tRA inhibited UV induction of c-Jun protein and, consequently, AP-1. c-Jun protein inhibition occurred via a posttranscriptional mechanism, since tRA did not inhibit UV induction of c-Jun mRNA. These data demonstrate, for the first time, activation of MAP kinase pathways in humans in vivo, and reveal a novel posttranscriptional mechanism by which tRA antagonizes UV activation of AP-1 by inhibiting c-Jun protein induction. Inhibition of c-Jun induction likely contributes to the previously reported prevention by tRA of UV induction of AP-1-regulated matrix-degrading metalloproteinases in human skin.

  6. Relationship Between Cortical Thickness and Functional Activation in the Early Blind

    PubMed Central

    Anurova, Irina; Renier, Laurent A.; De Volder, Anne G.; Carlson, Synnöve; Rauschecker, Josef P.

    2015-01-01

    Early blindness results in both structural and functional changes of the brain. However, these changes have rarely been studied in relation to each other. We measured alterations in cortical thickness (CT) caused by early visual deprivation and their relationship with cortical activity. Structural and functional magnetic resonance imaging was performed in 12 early blind (EB) humans and 12 sighted controls (SC). Experimental conditions included one-back tasks for auditory localization and pitch identification, and a simple sound-detection task. Structural and functional data were analyzed in a whole-brain approach and within anatomically defined regions of interest in sensory areas of the spared (auditory) and deprived (visual) modalities. Functional activation during sound-localization or pitch-identification tasks correlated negatively with CT in occipital areas of EB (calcarine sulcus, lingual gyrus, superior and middle occipital gyri, and cuneus) and in nonprimary auditory areas of SC. These results suggest a link between CT and activation and demonstrate that the relationship between cortical structure and function may depend on early sensory experience, probably via selective pruning of exuberant connections. Activity-dependent effects of early sensory deprivation and long-term practice are superimposed on normal maturation and aging. Together these processes shape the relationship between brain structure and function over the lifespan. PMID:24518755

  7. Aucubin, a naturally occurring iridoid glycoside inhibits TNF-α-induced inflammatory responses through suppression of NF-κB activation in 3T3-L1 adipocytes.

    PubMed

    Park, Kyoung Sik

    2013-06-01

    Obesity is closely associated with a state of chronic, low-grade inflammation characterized by abnormal cytokine production and activation of inflammatory signaling pathways in adipose tissue. Tumor necrosis factor (TNF)-α is chronically elevated in adipose tissues of obese rodents and humans. Increased levels of TNF-α are implicated in the induction of atherogenic adipokines, such as plasminogen activator inhibitor (PAI)-1, adipose-tissue-derived monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-6. Aucubin, an iridoid glycoside existing in medicinal plants, has been reported to show an anti-inflammatory activity by suppression of TNF-α production in murine macrophages. The present study is aimed to investigate the effects of aucubin on TNF-α-induced atherogenic changes of the adipokines in differentiated 3T3-L1 cells. Aucubin significantly inhibited TNF-α-induced secretion and mRNA synthesis of the atherogenic adipokines including PAI-1, MCP-1, and IL-6. Further investigation of the molecular mechanism revealed that pretreatment with aucubin suppressed extracellular signal-regulated kinase (ERK) activation, inhibitory kappa Bα (IκBα) degradation, and subsequent nuclear factor kappa B (NF-κB) activation. These findings suggest that aucubin may improve obesity-induced atherosclerosis by attenuating TNF-α-induced inflammatory responses.

  8. Naturally occurring polyphenol, morin hydrate, inhibits enzymatic activity of N-methylpurine DNA glycosylase, a DNA repair enzyme with various roles in human disease.

    PubMed

    Dixon, Monica; Woodrick, Jordan; Gupta, Suhani; Karmahapatra, Soumendra Krishna; Devito, Stephen; Vasudevan, Sona; Dakshanamurthy, Sivanesan; Adhikari, Sanjay; Yenugonda, Venkata M; Roy, Rabindra

    2015-03-01

    Interest in the mechanisms of DNA repair pathways, including the base excision repair (BER) pathway specifically, has heightened since these pathways have been shown to modulate important aspects of human disease. Modulation of the expression or activity of a particular BER enzyme, N-methylpurine DNA glycosylase (MPG), has been demonstrated to play a role in carcinogenesis and resistance to chemotherapy as well as neurodegenerative diseases, which has intensified the focus on studying MPG-related mechanisms of repair. A specific small molecule inhibitor for MPG activity would be a valuable biochemical tool for understanding these repair mechanisms. By screening several small molecule chemical libraries, we identified a natural polyphenolic compound, morin hydrate, which inhibits MPG activity specifically (IC50=2.6μM). Detailed mechanism analysis showed that morin hydrate inhibited substrate DNA binding of MPG, and eventually the enzymatic activity of MPG. Computational docking studies with an x-ray derived MPG structure as well as comparison studies with other structurally-related flavonoids offer a rationale for the inhibitory activity of morin hydrate observed. The results of this study suggest that the morin hydrate could be an effective tool for studying MPG function and it is possible that morin hydrate and its derivatives could be utilized in future studies focused on the role of MPG in human disease.

  9. Architecture and evolution of an Early Permian carbonate complex on a tectonically active island in east-central California

    USGS Publications Warehouse

    Stevens, Calvin H.; Magginetti, Robert T.; Stone, Paul

    2015-01-01

    The newly named Upland Valley Limestone represents a carbonate complex that developed on and adjacent to a tectonically active island in east-central California during a brief interval of Early Permian (late Artinskian) time. This lithologically unique, relatively thin limestone unit lies within a thick sequence of predominantly siliciclastic rocks and is characterized by its high concentration of crinoidal debris, pronounced lateral changes in thickness and lithofacies, and a largely endemic fusulinid fauna. Most outcrops represent a carbonate platform and debris derived from it and shed downslope, but another group of outcrops represents one or possibly more isolated carbonate buildups that developed offshore from the platform. Tectonic activity in the area occurred before, probably during, and after deposition of this short-lived carbonate complex.

  10. The interaction between early-life body size and physical activity on risk of breast cancer

    PubMed Central

    Oh, Hannah; Boeke, Caroline E.; Tamimi, Rulla M.; Smith-Warner, Stephanie A.; Wang, Molin; Willett, Walter C.; Eliassen, A. Heather

    2014-01-01

    While early-life body leanness is associated with increased breast cancer risk, early-life physical activity may protect against breast cancer. We examined whether the excess risk among lean girls is modified by their levels of prior, concurrent, or future physical activity. We conducted an analysis among 74,723 women in the Nurses’ Health Study II (follow-up 1997–2011). Participants recalled their body size at ages 5, 10, and 20 years in 1989 using a 9-level pictogram (level 1: most lean). In 1997, they reported adolescent levels of physical activity (ages 12–13 and 14–17 years). Cox proportional hazards models estimated the overall association of body size with breast cancer risk and assessed interactions of adolescent physical activity with body size at three different age periods (5–10, 10–20, and 20 years), adjusting for early-life and adult risk factors for breast cancer. Regardless of levels of adolescent physical activity, early-life body leanness (level 1–2 vs. 4.5+) was significantly associated with higher breast cancer risk. The association was slightly attenuated among those who were active (60+ MET-hr/wk) during adolescence compared to those who were inactive (<30 MET-hr/wk) (body size at ages 5–10 years: hazard ratio=1.37, 95% confidence interval=1.04–1.81 vs. 1.66, 1.29–2.12), but the interaction was not significant (p=0.72). The results were similar for body size at three different age periods. Being lean during early life is a risk factor for breast cancer among both inactive and active girls. Adolescent physical activity did not significantly modify the association, although some interaction cannot be excluded. PMID:25335465

  11. Trajectories of Pure and Co-Occurring Internalizing and Externalizing Problems from Age 2 to Age 12: Findings from the National Institute of Child Health and Human Development Study of Early Child Care

    ERIC Educational Resources Information Center

    Fanti, Kostas A.; Henrich, Christopher C.

    2010-01-01

    How and why do internalizing and externalizing problems, psychopathological problems from different diagnostic classes representing separate forms of psychopathology, co-occur in children? We investigated the development of pure and co-occurring internalizing and externalizing problems from ages 2 to 12 with the use of latent class growth…

  12. Early peroxisome proliferator-activated receptor gamma regulated genes involved in expansion of pancreatic beta cell mass

    PubMed Central

    2011-01-01

    Background The progression towards type 2 diabetes depends on the allostatic response of pancreatic beta cells to synthesise and secrete enough insulin to compensate for insulin resistance. The endocrine pancreas is a plastic tissue able to expand or regress in response to the requirements imposed by physiological and pathophysiological states associated to insulin resistance such as pregnancy, obesity or ageing, but the mechanisms mediating beta cell mass expansion in these scenarios are not well defined. We have recently shown that ob/ob mice with genetic ablation of PPARγ2, a mouse model known as the POKO mouse failed to expand its beta cell mass. This phenotype contrasted with the appropriate expansion of the beta cell mass observed in their obese littermate ob/ob mice. Thus, comparison of these models islets particularly at early ages could provide some new insights on early PPARγ dependent transcriptional responses involved in the process of beta cell mass expansion Results Here we have investigated PPARγ dependent transcriptional responses occurring during the early stages of beta cell adaptation to insulin resistance in wild type, ob/ob, PPARγ2 KO and POKO mice. We have identified genes known to regulate both the rate of proliferation and the survival signals of beta cells. Moreover we have also identified new pathways induced in ob/ob islets that remained unchanged in POKO islets, suggesting an important role for PPARγ in maintenance/activation of mechanisms essential for the continued function of the beta cell. Conclusions Our data suggest that the expansion of beta cell mass observed in ob/ob islets is associated with the activation of an immune response that fails to occur in POKO islets. We have also indentified other PPARγ dependent differentially regulated pathways including cholesterol biosynthesis, apoptosis through TGF-β signaling and decreased oxidative phosphorylation. PMID:22208362

  13. Inhibition of pro-inflammatory markers in primary bone marrow-derived mouse macrophages by naturally occurring flavonoids: analysis of the structure-activity relationship.

    PubMed

    Comalada, Mònica; Ballester, Isabel; Bailón, Elvira; Sierra, Saleta; Xaus, Jordi; Gálvez, Julio; de Medina, Fermín Sánchez; Zarzuelo, Antonio

    2006-10-16

    Flavonoids possess several biological/pharmacological activities including anticancer, antimicrobial, antiviral, anti-inflammatory, immunomodulatory and antioxidant. The aim of this study was to evaluate the effect of flavonoids on macrophage physiology. For this purpose we selected some flavonoids belonging to the most common and abundant groups (flavonols--quercetin and kaempferol; flavones--diosmetin, apigenin, chrysin and luteolin; isoflavones--genistein and daidzein and flavanones--hesperetin). We decided to use primary bone marrow-derived macrophages (BMDM) as cellular model, since they represent a homogenous, non-transformed population of macrophages that can be stimulated in vitro to proliferate by macrophage colony-stimulating factor (M-CSF) or activated by LPS. In this regard, we demonstrated that most of the flavonoids assayed reduce macrophage M-CSF-induced proliferation without affecting cellular viability. Moreover, some flavonoids also inhibit TNFalpha production as well as iNOS expression and NO production in LPS-activated macrophages, an effect that has been associated with the inhibition of the NF-kappaB pathway. We also found that luteolin and quercetin are able to stimulate the expression of the anti-inflammatory cytokine IL-10 at low concentrations (<50microM). Analysis of the structure-activity relationship showed that four hydroxylations at positions 5, 7, 3' and 4', together with the double bond at C(2)-C(3) and the position of the B ring at 2, seem to be necessary for the highest anti-inflammatory effect.

  14. SUMOylation of the inducible (c-Fos:c-Jun)/AP-1 transcription complex occurs on target promoters to limit transcriptional activation.

    PubMed

    Tempé, D; Vives, E; Brockly, F; Brooks, H; De Rossi, S; Piechaczyk, M; Bossis, G

    2014-02-13

    The inducible proto-oncogenic (c-Fos:c-Jun)/AP-1 transcription complex binds 12-O-tetradecanoylphorbol 13-acetate (TPA)-responsive elements (TRE) in its target genes. It is tightly controlled at multiple levels to avoid the deleterious effects of its inappropriate activation. In particular, SUMOylation represses its transactivation capacity in transient reporter assays using constitutively expressed proteins. This led to the presumption that (c-Fos:c-Jun)/AP-1 SUMOylation would be required to turn-off transcription of its target genes, as proposed for various transcription factors. Instead, thanks to the generation of an antibody specific for SUMO-modified c-Fos, we provide here direct evidence that SUMOylated c-Fos is present on a stably integrated reporter TPA-inducible promoter at the onset of transcriptional activation and colocalizes with RNA polymerase II within chromatin. Interestingly, (c-Fos:c-Jun)/AP-1 SUMOylation limits reporter gene induction, as well as the appearance of active transcription-specific histone marks on its promoter. Moreover, non-SUMOylatable mutant (c-Fos:c-Jun)/AP-1 dimers accumulate to higher levels on their target promoter, suggesting that SUMOylation might facilitate the release of (c-Fos:c-Jun)/AP-1 from promoters. Finally, activation of GADD153, an AP-1 target gene, is also associated with a rapid increase in SUMOylation at the level of its TRE and c-Fos SUMOylation dampens its induction by TPA. Taken together, our data suggest that SUMOylation could serve to buffer transcriptional activation of AP-1 target genes.

  15. Base excision repair in early zebrafish development: evidence for DNA polymerase switching and standby AP endonuclease activity.

    PubMed

    Fortier, Sean; Yang, Xiaojie; Wang, Yi; Bennett, Richard A O; Strauss, Phyllis R

    2009-06-16

    The base excision repair (BER) pathway recognizes and repairs most nonbulky lesions, uracil and abasic (AP) sites in DNA. Several participants are embryonic lethals in knockout mice. Since the pathway has never been investigated during embryogenesis, we characterized the first three steps of BER in zebrafish extracts from unfertilized eggs, embryos at different developmental stages, and adults. Using a 45-mer double-stranded substrate with a U/G mispair at position 21, we showed that extracts from all stages are capable of performing BER. Before 3 days postfertilization (dpf), aphidicolin-sensitive polymerases perform most nucleotide insertion. In fact, eggs and early stage embryos lack DNA polymerase-beta protein. After the eggs have hatched at 3 dpf, an aphidicolin-resistant polymerase, probably DNA polymerase-beta, becomes the primary polymerase. Previously, we showed that when the zebrafish AP endonuclease protein (ZAP1) level is knocked down, embryos cease dividing after the initial phase of rapid proliferation and die without apoptosis shortly thereafter. Nevertheless, extracts from embryos in which ZAP1 has been largely depleted process substrate as well as extracts from control embryos. Since apex1 and apex2 are both strongly expressed in early embryos relative to adults, these data indicate that both may play important roles in DNA repair in early development. In brief, the major differences in BER performed by early stage embryos and adults are the absence of DNA polymerase-beta, leading to predominance of replicative polymerases, and the presence of backup Mg(2+)-dependent endonuclease activity in early stage embryos. The switch to normal, adult BER occurs fully when the embryos hatch from the chorionic membrane and encounter normal oxidative stress.

  16. Modeling and analysis of early events in T-lymphocyte antigen-activated intracellular-signaling pathways

    NASA Astrophysics Data System (ADS)

    Zheng, Yanan; Balakrishnan, Venkataramanan; Buzzard, Greg; Geahlen, Robert; Harrison, Marietta; Rundell, Ann

    2005-12-01

    The T-cell antigen-activated signaling pathway is a highly regulated intracellular biochemical system that is crucial for initiating an appropriate adaptive immune response. To improve the understanding of the complex regulatory mechanisms controlling the early events in T-cell signaling, a detailed mathematical model was developed that utilizes ordinary differential equations to describe chemical reactions of the signaling pathway. The model parameter values were constrained by experimental data on the activation of a specific signaling intermediate and indicated an initial rapid cascade of phosphorylation events followed by a comparatively slow signal downregulation. Nonlinear analysis of the model suggested that thresholding and bistability occur as a result of the embedded positive and negative feedback loops within the model. These nonlinear system properties may enhance the T-cell receptor specificity and provide sub-threshold noise filtering with switch-like behavior to ensure proper cell response. Additional analysis using a reduced second-order model led to further understanding of the observed system behavior. Moreover, the interactions between the positive and negative feedback loops enabled the model to exhibit, among a variety of other feasible dynamics, a sustained oscillation that corresponds to a stable limit cycle in the two-dimensional phase plane. Quantitative analysis in this paper has helped identify potential regulatory mechanisms in the early T-cell signaling events. This integrated approach provides a framework to quantify and discover the ensemble of interconnected T-cell antigen-activated signaling pathways from limited experimental data.

  17. Phytochemical screening, antioxidant and antibacterial activities of extracts prepared from different tissues of Schinus terebinthifolius Raddi that occurs in the coast of Bahia, Brazil

    PubMed Central

    D’Sousa’ Costa, Cinara Oliveira; Ribeiro, Paulo Roberto; Loureiro, Marta Bruno; Simões, Rafael Conceição; de Castro, Renato Delmondez; Fernandez, Luzimar Gonzaga

    2015-01-01

    Background: Schinus terebinthifolius is widely used in traditional medicine by Brazilian quilombola and indigenous communities for treatment of several diseases. Extracts from different tissues are being used to produce creams to treat cervicitis and cervicovaginitis. However, most studies are limited to the assessment of the essential oils and extracts obtained from the leaves. Objective: The aim was to evaluate antioxidant and antibacterial activities, to assess the phytochemical profile and to quantify total phenolic compounds of various extracts prepared from S. terebinthifolius grown in the coast of Bahia, Brazil. Materials and Methods: Extracts were obtained by hot continuous extraction (soxhlet) and by maceration. Quantification of phenolic compounds was performed using the Folin-Ciocalteu method and antioxidant properties were assessed by 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay. Phytochemical screening was performed as described by in the literature and antibacterial activity against Enterococcus faecalis (ATCC 29212) was determined by the microdilution broth assay. Results: Extraction method greatly affected the metabolite profile of the extracts. Antioxidant activity varied between 21.92% and 85.76%, while total phenols ranged between 5.44 and 309.03 mg EAG/g of extract. Leaf extract obtained with soxhlet showed minimum inhibitory concentration (MIC) of 15.62 μg/mL, while stem extract obtained by maceration was able to inhibit the growth of E. faecalis at 62.5 μg/mL. Stem bark extracts showed a MIC of 500 μg/mL for both extraction methods, while no inhibition was observed for fruit extracts. Conclusion: In general, total phenolic content, antioxidant and antibacterial activities were higher in samples obtained by soxhlet. Our results provide important clues in order to identify alternative sources of bioactive compounds that can be used to develop new drugs. PMID:26246739

  18. An investigation of herpes simplex virus promoter activity compatible with latency establishment reveals VP16-independent activation of immediate-early promoters in sensory neurones.

    PubMed

    Proença, João T; Coleman, Heather M; Nicoll, Michael P; Connor, Viv; Preston, Christopher M; Arthur, Jane; Efstathiou, Stacey

    2011-11-01

    Herpes simplex virus (HSV) type-1 establishes lifelong latency in sensory neurones and it is widely assumed that latency is the consequence of a failure to initiate virus immediate-early (IE) gene expression. However, using a Cre reporter mouse system in conjunction with Cre-expressing HSV-1 recombinants we have previously shown that activation of the IE ICP0 promoter can precede latency establishment in at least 30% of latently infected cells. During productive infection of non-neuronal cells, IE promoter activation is largely dependent on the transactivator VP16 a late structural component of the virion. Of significance, VP16 has recently been shown to exhibit altered regulation in neurones; where its de novo synthesis is necessary for IE gene expression during both lytic infection and reactivation from latency. In the current study, we utilized the Cre reporter mouse model system to characterize the full extent of viral promoter activity compatible with cell survival and latency establishment. In contrast to the high frequency activation of representative IE promoters prior to latency establishment, cell marking using a virus recombinant expressing Cre under VP16 promoter control was very inefficient. Furthermore, infection of neuronal cultures with VP16 mutants reveals a strong VP16 requirement for IE promoter activity in non-neuronal cells, but not sensory neurones. We conclude that only IE promoter activation can efficiently precede latency establishment and that this activation is likely to occur through a VP16-independent mechanism. PMID:21752961

  19. Synergistic activity between the delta-opioid agonist SNC80 and amphetamine occurs via a glutamatergic NMDA-receptor dependent mechanism

    PubMed Central

    Bosse, Kelly E.; Jutkiewicz, Emily M.; Schultz, Kristin N.; Mabrouk, Omar S.; Kennedy, Robert T.; Gnegy, Margaret E.; Traynor, John R.

    2014-01-01

    Glutamate is known to cause the release of dopamine through a Ca2+-sensitive mechanism that involves activation of NMDA ionotropic glutamate receptors. In the current study, we tested the hypothesis that the delta opioid agonist SNC80 acts indirectly, via the glutamatergic system, to enhance both amphetamine-stimulated dopamine efflux from striatal preparations and amphetamine-stimulated locomotor activity. SNC80 increased extracellular glutamate content, which was accompanied by a concurrent decrease in GABA levels. Inhibition of NMDA signaling with the selective antagonist MK801 blocked the enhancement of both amphetamine-induced dopamine efflux and hyperlocomotion observed with SNC80 pretreatment. Addition of exogenous glutamate also potentiated amphetamine-stimulated dopamine efflux in a Mg2+- and MK801-sensitive manner. After removal of Mg2+ to relieve the ion conductance inhibition of NMDA receptors, SNC80 both elicited dopamine release alone and produced a greater enhancement of amphetamine-evoked dopamine efflux. The action of SNC80 to enhance amphetamine-evoked dopamine efflux was mimicked by the GABAB antagonist 2-hydroxysaclofen. These cumulative findings suggest SNC80 modulates amphetamine-stimulated dopamine efflux through an intra-striatal mechanism involving inhibition of GABA transmission leading to the local release of glutamate followed by subsequent activation of NMDA receptors. PMID:24035916

  20. A thermal active restrained shrinkage ring test to study the early age concrete behaviour of massive structures

    SciTech Connect

    Briffaut, M.; Benboudjema, F.; Nahas, G.

    2011-01-15

    In massive concrete structures, cracking may occur during hardening, especially if autogenous and thermal strains are restrained. The concrete permeability due to this cracking may rise significantly and thus increase leakage (in tank, nuclear containment...) and reduce the durability. The restrained shrinkage ring test is used to study the early age concrete behaviour (delayed strains evolution and cracking). This test shows, at 20 {sup o}C and without drying, for a concrete mix which is representative of a French nuclear power plant containment vessel (w/c ratio equal to 0.57), that the amplitude of autogenous shrinkage (about 40 {mu}m/m for the studied concrete mix) is not high enough to cause cracking. Indeed, in this configuration, thermal shrinkage is not significant, whereas this is a major concern for massive structures. Therefore, an active test has been developed to study cracking due to restrained thermal shrinkage. This test is an evolution of the classical restrained shrinkage ring test. It allows to take into account both autogenous and thermal shrinkages. Its principle is to create the thermal strain effects by increasing the temperature of the brass ring (by a fluid circulation) in order to expand it. With this test, the early age cracking due to restrained shrinkage, the influence of reinforcement and construction joints have been experimentally studied. It shows that, as expected, reinforcement leads to an increase of the number of cracks but a decrease of crack widths. Moreover, cracking occurs preferentially at the construction joint.

  1. Active mountain building in Taiwan in comparison to the early postcollisional evolution of the Alps

    NASA Astrophysics Data System (ADS)

    Ustaszewski, K.; Suppe, J.; Wu, Y.-M.; Huang, S.-T.

    2009-04-01

    Taiwan represent the subaerial part of an active, bivergent thrust belt resulting from the oblique collision between the Luzon island arc of the Philippine Sea Plate and the passive margin of the Eurasian Plate since about 4 to 6.5 Ma. This collision followed the initially intraoceanic subduction of the South China Sea lithosphere below the Philippine Sea Plate, which commenced c. 15 Ma ago and which still prevails south of Taiwan in the Manila accretionary wedge. Considering the collision between Eurasia and the Luzon island arc as one between a large continental plate and a microplate, many analogies can be inferred between currently ongoing mountain building processes in Taiwan and those that occurred in the Alps following closure of the Alpine Tethys in the late Palaeogene. Based on new crustal-scale cross-sections and high-resolution earthquake tomography, we provide an overview of Taiwan's kinematics and compare this to the late Palaeogene evolution of the Alps, a time that marked its transition from an accretionary to a collisional, bivergent orogen. The Taiwan fold-and thrust belt is characterised by actively growing topography, crustal accretion by thrust propagation towards the foreland, a subsiding foreland basin and ongoing tectonic exhumation of metamorphosed continental basement and cover in the retrowedge. Exhumation is controlled by the development of a crustal-scale backfold that overprints earlier fabrics related to foreland-facing transport. Backthrusts within the Eurasian basement that were active at greenschist-facies conditions facilitated exhumation. 40Ar/39Ar ages on synkinematically deformed biotites suggest that backthrusting started as early as between ca. 3-4 Ma, i.e. shortly after or concomitant with the onset of collision between Eurasian passive margin and Luzon island arc. At the internal side of the backfold, blueschist-facies units that likely represent subducted forearc lithosphere are preserved. This structural setting bears some

  2. Synergism between insecticides permethrin and propoxur occurs through activation of presynaptic muscarinic negative feedback of acetylcholine release in the insect central nervous system.

    PubMed

    Corbel, Vincent; Stankiewicz, Maria; Bonnet, Julien; Grolleau, Françoise; Hougard, Jean Marc; Lapied, Bruno

    2006-07-01

    Although synergism between pesticides has been widely documented, the physiological mechanisms by which an insecticide synergizes another remains unclear. Toxicological and electrophysiological studies were carried out on two susceptible pest species (the mosquito Culex quinquefasciatus and the cockroach Periplaneta americana) to understand better the physiological process involved in pyrethroid and carbamate interactions. Larval bioassays were conducted with the susceptible reference strain SLAB of C. quinquefasciatus to assess the implication of multi-function oxidases and non-specific esterases in insecticide detoxification and synergism. Results showed that the general theory of synergism (competition between pesticides for a common detoxification enzyme) was unlikely to occur in the SLAB strain since the level of synergy recorded between permethrin and propoxur was unchanged in the presence of piperonyl butoxide and tribufos, two inhibitors of oxidases and esterases, respectively (synergism ratios were similar with and without synergists). We also showed that addition of a sub-lethal concentration of nicotine significantly increased the toxicity of permethrin and propoxur at the lower range of the dose-mortality regression lines, suggesting the manifestation of important physiological disruptions at synaptic level. The effects of both permethrin and propoxur were studied on the cercal-afferent giant-interneuron synapses in the terminal abdominal ganglion of the cockroach P. americana using the single-fibre oil-gap method. We demonstrated that permethrin and propoxur increased drastically the ACh concentration within the synaptic cleft, which thereby stimulated a negative feedback of ACh release. Atropine, a muscarinic receptor antagonist, reversed the effect of permethrin and propoxur mixtures. This demonstrates the implication of the presynaptic muscarinic receptors in the negative feedback regulation process and in synergism. Based on these findings, we

  3. Detection of Early Morning Daily Activities with Static Home and Wearable Wireless Sensors

    NASA Astrophysics Data System (ADS)

    Ince, Nuri Firat; Min, Cheol-Hong; Tewfik, Ahmed; Vanderpool, David

    2007-12-01

    This paper describes a flexible, cost-effective, wireless in-home activity monitoring system for assisting patients with cognitive impairments due to traumatic brain injury (TBI). The system locates the subject with fixed home sensors and classifies early morning bathroom activities of daily living with a wearable wireless accelerometer. The system extracts time- and frequency-domain features from the accelerometer data and classifies these features with a hybrid classifier that combines Gaussian mixture models and a finite state machine. In particular, the paper establishes that despite similarities between early morning bathroom activities of daily living, it is possible to detect and classify these activities with high accuracy. It also discusses system training and provides data to show that with proper feature selection, accurate detection and classification are possible for any subject with no subject specific training.

  4. Responding to the Challenges of Active Citizenship through the Revised UK Early Years Foundation Stage Curriculum

    ERIC Educational Resources Information Center

    Baker, Fiona S.

    2013-01-01

    The revised UK Early Years Foundation Stage (EYFS) now places a stronger emphasis on personal, social and emotional development (PSED) as one of its three prime areas. PSED has three characteristics of learning: active learning, creating and thinking critically, and playing and exploring. These aspects of the revised EYFS closely align with the…

  5. Investigating Pre-Service Early Childhood Teachers' Attitudes towards the Computer Based Education in Science Activities

    ERIC Educational Resources Information Center

    Yilmaz, Nursel; Alici, Sule

    2011-01-01

    The purpose of this study was to investigate pre-service early childhood teachers' attitudes towards using Computer Based Education (CBE) while implementing science activities. More specifically, the present study examined the effect of different variables such as gender, year in program, experience in preschool, owing a computer, and the…

  6. The Complete Resource Book: An Early Childhood Curriculum. Over 2000 Activities and Ideas.

    ERIC Educational Resources Information Center

    Schiller, Pam; Hastings, Kay

    This book is a collection of developmentally appropriate activities for 3- to 5-year-olds, designed to be easily integrated into the daily schedule of an early childhood program. The book's introduction describes the collection's theme units, delineates typical half- and full-day schedules, and discusses the arrangement and management of classroom…

  7. Promoting an "Active Start" for Young Children: Developing Competent and Confident Early Movers

    ERIC Educational Resources Information Center

    Goodway, Jacqueline D.; Wall, Sarah; Getchell, Nancy

    2009-01-01

    With childhood obesity and physical inactivity at an all-time high, parents and physical educators alike must look to the early years to promote competent and confident young movers. Popular opinion believes that children are naturally active and motor skill development progresses as a normal function of getting older. However, if one looks at…

  8. Role of Parent Literacy and Numeracy Expectations and Activities in Predicting Early Numeracy Skills

    ERIC Educational Resources Information Center

    Segers, Eliane; Kleemans, Tijs; Verhoeven, Ludo

    2015-01-01

    The home numeracy environment (i.e., parents' numeracy expectations and activities), is related to early numeracy in young children. As recent studies have shown that both cognitive and linguistic factors play an important role in predicting numeracy development, it may be assumed that rather than the home "numeracy" environment, the…

  9. Early Behavioral Intervention Is Associated with Normalized Brain Activity in Young Children with Autism

    ERIC Educational Resources Information Center

    Dawson, Geraldine; Jones, Emily J. H.; Merkle, Kristen; Venema, Kaitlin; Lowy, Rachel; Faja, Susan; Kamara, Dana; Murias, Michael; Greenson, Jessica; Winter, Jamie; Smith, Milani; Rogers, Sally J.; Webb, Sara J.

    2012-01-01

    Objective: A previously published randomized clinical trial indicated that a developmental behavioral intervention, the Early Start Denver Model (ESDM), resulted in gains in IQ, language, and adaptive behavior of children with autism spectrum disorder. This report describes a secondary outcome measurement from this trial, EEG activity. Method:…

  10. Does Father Absence Place Daughters at Special Risk for Early Sexual Activity and Teenage Pregnancy?

    ERIC Educational Resources Information Center

    Ellis, Bruce J.; Bates, John E.; Dodge, Kenneth A.; Fergusson, David M.; Horwood, L. John; Pettit, Gregory S.; Woodward, Lianne

    2003-01-01

    Longitudinal studies in two countries investigated impact of father absence on girls' early sexual activity (ESA) and teenage pregnancy. Findings indicated that greater exposure to father absence strongly related to elevated ESA and adolescent pregnancy risk. Elevated risk was not explained (U.S. sample) or only partly explained (New Zealand…

  11. Early Activity of Cometary Species from ROSINA/DFMS at 67P/ Churyumov-Gerasimenko

    NASA Astrophysics Data System (ADS)

    Hässig, Myrtha; Fuselier, Stephen A.; Altwegg, Kathrin; Balsiger, Hans; Berthelier, Jean-Jacques; Bieler, André; Calmonte, Ursina; Dhooghe, Frederik; Fiethe, Björn; Gasc, Sébastien; Gombosi, Tamas I.; Jäckel, Annette; Korth, Axel; Le Roy, Léna; Rème, Henri; Rubin, Martin; Tzou, Chia-Yu; Wurz, Peter

    2014-11-01

    The European Space Agency’s Rosetta spacecraft arrived after a journey of more than 10 years at comet 67P/Churyumov-Gerasimenko. ROSINA is an instrument package on board Rosetta. It consists of two mass spectrometers and a COmetary Pressure Sensor (COPS). The two mass spectrometers, the Double Focusing Mass Spectrometer (DFMS) and the Reflectron Time of Flight (RTOF) complement each other with high mass resolution (e.g to resolve 13C from CH), high dynamic range (to detect low abundant isotopes and species), high mass range (to detect organics), and high time resolution. ROSINA is designed to measure the neutral gas and plasma composition in the coma of 67P/Churyumov-Gerasimenko in addition to the physical properties of the neutral component of the coma. For the first time, a comet can be observed in situ from its early activity towards and after perihelion. Little is known about what drives initial cometary activity very far from the Sun. Remote sensing observations to date are highly constrained to a limited number of a few bright comets (e.g. Hale-Bopp) and a limited number of species. Rosetta provides the first measurements of the early activity of a comet in situ and detected the first cometary molecules early August. We will focus on early activity of cometary species from the high resolution mass spectrometer ROSINA/DFMS.

  12. Sixty Minutes of Physical Activity per Day Included within Preschool Academic Lessons Improves Early Literacy

    ERIC Educational Resources Information Center

    Kirk, Stacie M.; Kirk, Erik P.

    2016-01-01

    Background: The effects of increases in physical activity (PA) on early literacy skills in preschool children are not known. Methods: Fifty-four African-American preschool children from a low socioeconomic urban Head Start participated over 8 months. A 2-group, quasi-experimental design was used with one preschool site participating in the PA…

  13. Sources of Continuity and Change in Activity Level in Early Childhood

    ERIC Educational Resources Information Center

    Saudino, Kimberly J.

    2012-01-01

    Actigraphs and parent and observer ratings were used to explore genetic influences on continuity and change in activity level (AL) in early childhood. Over 300 pairs of twins wore actigraphs for a 48-hr period in the home and laboratory at ages 2 and 3. AL was genetically influenced at both ages with little evidence of differential heritability…

  14. Psychosocial Correlates of Physical and Sedentary Activities of Early Adolescent Youth

    ERIC Educational Resources Information Center

    Rusby, Julie C.; Westling, Erika; Crowley, Ryann; Light, John M.

    2014-01-01

    This study examines physical and sedentary activities of early adolescent boys and girls using Ecological Momentary Assessment (EMA), a method that can link mood and behaviors in specific social situations. Twenty-seven assessments were collected across 7 days from 82 participating adolescents, three times in seventh grade and one time in eighth…

  15. Mothers' Knowledge of Early Adolescents' Activities following the Middle School Transition and Pubertal Maturation

    ERIC Educational Resources Information Center

    Laird, Robert D.; Marrero, Matthew D.

    2011-01-01

    This study tested a sequential mediation model to determine whether experiences, social cognitions, or parent-adolescent interactional processes account for lower levels of mothers' knowledge of adolescents' whereabouts and activities following early adolescents' transition into middle school (MS) and pubertal development. Cross-sectional data…

  16. Environmental Influences on Preschoolers' Physical Activity Levels in Various Early-Learning Facilities

    ERIC Educational Resources Information Center

    Vanderloo, Leigh M.; Tucker, Patricia; Johnson, Andrew M.; Burke, Shauna M.; Irwin, Jennifer D.

    2015-01-01

    Purpose: This study aimed to: (a) compare the physical activity (PA) levels (i.e., moderate-to-vigorous PA [MVPA] and total PA [TPA]) of preschoolers in 3 different early-learning environments (center-based childcare, home-based childcare, and full-day kindergarten [FDK]); and (b) assess which characteristics (e.g., play equipment, policies, etc.)…

  17. Romantic and Sexual Activities, Parent-Adolescent Stress, and Depressive Symptoms among Early Adolescent Girls

    ERIC Educational Resources Information Center

    Davila, Joanne; Stroud, Catherine B.; Starr, Lisa R.; Miller, Melissa Ramsay; Yoneda, Athena; Hershenberg, Rachel

    2009-01-01

    Building on evidence that romantic experiences are associated with depressive symptoms in adolescence, we examined their bidirectional association, as well as the role of sexual activity and parent-adolescent stress in their association. Data were collected from 71 early adolescent girls (M age 13.45 years; SD = 0.68) and their primary caregiver…

  18. Initiating Sexual Experiences: How Do Young Adolescents Make Decisions Regarding Early Sexual Activity?

    ERIC Educational Resources Information Center

    Michels, Tricia M.; Kropp, Rhonda Y.; Eyre, Stephen L.; Halpern-Felsher, Bonnie L.

    2005-01-01

    Understanding how young adolescents make decisions to engage in early sexual activities is vital for intervention efforts aimed at fostering positive youth development and reducing the negative outcomes of adolescent sexual behavior. In-depth interviews with 42 suburban, mostly White, ninth-grade adolescents (52% females, mean age=14.1, SD=.45)…

  19. Factors Influencing Attitudes toward Sexual Activity among Early Adolescents in Japan

    ERIC Educational Resources Information Center

    Nagamatsu, Miyuki; Yamawaki, Niwako; Sato, Takeshi; Nakagawa, Aki; Saito, Hisako

    2013-01-01

    The purpose of this study was to examine factors influencing attitudes toward sexual activity among early adolescents in Japan. A total of 1,551 students aged 12 to 14 years at 4 junior high schools were divided into either a conservative or liberal group. Results of chi-square tests showed that the liberal group had higher percentages of students…

  20. Early-career registered nurses' participation in hospital quality improvement activities.

    PubMed

    Djukic, Maja; Kovner, Christine T; Brewer, Carol S; Fatehi, Farida K; Bernstein, Ilya

    2013-01-01

    We surveyed 2 cohorts of early-career registered nurses from 15 states in the US, 2 years apart, to compare their reported participation in hospital quality improvement (QI) activities. We anticipated differences between the 2 cohorts because of the growth of several initiatives for engaging nurses in QI. There were no differences between the 2 cohorts across 14 measured activities, except for their reported use of appropriate strategies to improve hand-washing compliance to reduce nosocomial infection rates. PMID:23192224

  1. Semantic Wavelet-Induced Frequency-Tagging (SWIFT) Periodically Activates Category Selective Areas While Steadily Activating Early Visual Areas

    PubMed Central

    Koenig-Robert, Roger; VanRullen, Rufin; Tsuchiya, Naotsugu

    2015-01-01

    Primate visual systems process natural images in a hierarchical manner: at the early stage, neurons are tuned to local image features, while neurons in high-level areas are tuned to abstract object categories. Standard models of visual processing assume that the transition of tuning from image features to object categories emerges gradually along the visual hierarchy. Direct tests of such models remain difficult due to confounding alteration in low-level image properties when contrasting distinct object categories. When such contrast is performed in a classic functional localizer method, the desired activation in high-level visual areas is typically accompanied with activation in early visual areas. Here we used a novel image-modulation method called SWIFT (semantic wavelet-induced frequency-tagging), a variant of frequency-tagging techniques. Natural images modulated by SWIFT reveal object semantics periodically while keeping low-level properties constant. Using functional magnetic resonance imaging (fMRI), we indeed found that faces and scenes modulated with SWIFT periodically activated the prototypical category-selective areas while they elicited sustained and constant responses in early visual areas. SWIFT and the localizer were selective and specific to a similar extent in activating category-selective areas. Only SWIFT progressively activated the visual pathway from low- to high-level areas, consistent with predictions from standard hierarchical models. We confirmed these results with criterion-free methods, generalizing the validity of our approach and show that it is possible to dissociate neural activation in early and category-selective areas. Our results provide direct evidence for the hierarchical nature of the representation of visual objects along the visual stream and open up future applications of frequency-tagging methods in fMRI. PMID:26691722

  2. Semantic Wavelet-Induced Frequency-Tagging (SWIFT) Periodically Activates Category Selective Areas While Steadily Activating Early Visual Areas.

    PubMed

    Koenig-Robert, Roger; VanRullen, Rufin; Tsuchiya, Naotsugu

    2015-01-01

    Primate visual systems process natural images in a hierarchical manner: at the early stage, neurons are tuned to local image features, while neurons in high-level areas are tuned to abstract object categories. Standard models of visual processing assume that the transition of tuning from image features to object categories emerges gradually along the visual hierarchy. Direct tests of such models remain difficult due to confounding alteration in low-level image properties when contrasting distinct object categories. When such contrast is performed in a classic functional localizer method, the desired activation in high-level visual areas is typically accompanied with activation in early visual areas. Here we used a novel image-modulation method called SWIFT (semantic wavelet-induced frequency-tagging), a variant of frequency-tagging techniques. Natural images modulated by SWIFT reveal object semantics periodically while keeping low-level properties constant. Using functional magnetic resonance imaging (fMRI), we indeed found that faces and scenes modulated with SWIFT periodically activated the prototypical category-selective areas while they elicited sustained and constant responses in early visual areas. SWIFT and the localizer were selective and specific to a similar extent in activating category-selective areas. Only SWIFT progressively activated the visual pathway from low- to high-level areas, consistent with predictions from standard hierarchical models. We confirmed these results with criterion-free methods, generalizing the validity of our approach and show that it is possible to dissociate neural activation in early and category-selective areas. Our results provide direct evidence for the hierarchical nature of the representation of visual objects along the visual stream and open up future applications of frequency-tagging methods in fMRI. PMID:26691722

  3. Developing an Active Play Resource for a Range of Australian Early Childhood Settings: Formative Findings and Recommendations

    ERIC Educational Resources Information Center

    Riethmuller, Annaleise; McKeen, Kim; Okely, Anthony D.; Bell, Colin; de Silva Sanigorski, Andrea

    2009-01-01

    Physical activity habits are established in early childhood. Increasing a child's fundamental movement skill confidence and competence may result in a trajectory of increased physical activity and a lower risk of becoming overweight. The evidence upon which the promotion of physical activity in early childhood settings is based is tenuous. This…

  4. The ESA-Facility MATROSHKA: A human phantom for dose measurements occurring in men being exposed during an Extra Vehicular Activity (EVA).

    NASA Astrophysics Data System (ADS)

    Reitz, G.

    The Matroshka facility basically consists of the upper part of a body phantom, com- posed of various tissue substitutes simulating the human body with respect to size, shape, position, mass density and nuclear interactions. At the site of the organs of interest, spaces are provided at the surface and in different depths inside the phan- tom to accommodate active and passive dosimeter packages for measurements of any radiation type. The phantom is mounted on a base structure containing the facility electronics and surrounded by a Carbon Fiber container providing structural support and fixation of the phantom and providing shielding thickness comparable to the EVA suit. The container and the base structure build up a sealed compartment. The objective of the proposed facility is to determine the empirical relations between measurable absorbed doses and the required tissue absorbed doses in a realistic hu- man phantom exposed to the concrete radiation field to be monitored. The radiation field during extravehicular activities (EVA) is that of the free space environment mod- ified only by the space suit. Since EVAs will form a substantial fraction of the work- schedule in the space station scenario, such measurements have highest priority. Once the ratios for the tissue absorbed doses and surface absorbed doses are known for a given radiation field around the human body, these values may be used in future expo- sures to determine the required tissue absorbed doses from measurements of surface absorbed doses, only. This technical presentation will describe the design of the MATROSHKA facility which is expected to be launched late 2003.

  5. Depletion of Intracellular Thiols and Increased Production of 4-Hydroxynonenal that Occur During Cryopreservation of Stallion Spermatozoa Lead to Caspase Activation, Loss of Motility, and Cell Death.

    PubMed

    Martin Muñoz, Patricia; Ortega Ferrusola, Cristina; Vizuete, Guillermo; Plaza Dávila, Maria; Rodriguez Martinez, Heriberto; Peña, Fernando J

    2015-12-01

    Oxidative stress has been linked to sperm death and the accelerated senescence of cryopreserved spermatozoa. However, the molecular mechanisms behind this phenomenon remain poorly understood. Reactive oxygen species (ROS) are considered relevant signaling molecules for sperm function, only becoming detrimental when ROS homeostasis is lost. We hereby hypothesize that a major component of the alteration of ROS homeostasis in cryopreserved spermatozoa is the exhaustion of intrinsic antioxidant defense mechanisms. To test this hypothesis, semen from seven stallions was frozen using a standard technique. The parameters of sperm quality (motility, velocity, and membrane integrity) and markers of sperm senescence (caspase 3, 4-hydroxynonenal, and mitochondrial membrane potential) were assessed before and after cryopreservation. Changes in the intracellular thiol content were also monitored. Cryopreservation caused significant increases in senescence markers as well as dramatic depletion of intracellular thiols to less than half of the initial values (P < 0.001) postthaw. Interestingly, very high and positive correlations were observed among thiol levels with sperm functionality postthaw: total motility (r = 0.931, P < 0.001), progressive motility (r = 0.904, P < 0.001), and percentage of live spermatozoa without active caspase 3 (r = 0.996, P < 0.001). In contrast, negative correlations were detected between active caspase 3 and thiol content both in living (r = -0.896) and dead (r = -0.940) spermatozoa; additionally, 4-hydroxynonenal levels were negatively correlated with thiol levels (r = -0.856). In conclusion, sperm functionality postthaw correlates with the maintenance of adequate levels of intracellular thiols. The accelerated senescence of thawed spermatozoa is related to oxidative and electrophilic stress induced by increased production of 4-hydroxynoneal in thawed samples once intracellular thiols are depleted.

  6. The Developmental Pathway From Pubertal Timing to Delinquency and Sexual Activity From Early to Late Adolescence

    PubMed Central

    Negriff, Sonya; Elizabeth, J. Susman; Trickett, Penelope K.

    2013-01-01

    There is strong evidence that early pubertal timing is associated with adolescent problem behaviors. However, there has been limited investigation of the mechanisms or developmental relationships. The present study examined longitudinal models incorporating pubertal timing, delinquency, and sexual activity in a sample of 454 adolescents (9–13 years old at enrollment; 47% females). Participants were seen for three assessments approximately 1 year apart. Characteristics of friendship networks (older friends, male friends, older male friends) were examined as mediators. Structural equation modeling was used to test these associations as well as temporal relationships between sexual activity and delinquency. Results showed that early pubertal timing at Time 1 was related to more sexual activity at Time 2, which was related to higher delinquency at Time 3, a trend mediation effect. None of the friendship variables mediated these associations. Gender or maltreatment status did not moderate the meditational pathways. The results also supported the temporal sequence of sexual activity preceding increases in delinquency. These findings reveal that early maturing adolescents may actively seek out opportunities to engage in sexual activity which appears to be risk for subsequent delinquency. PMID:21191640

  7. The developmental pathway from pubertal timing to delinquency and sexual activity from early to late adolescence.

    PubMed

    Negriff, Sonya; Susman, Elizabeth J; Trickett, Penelope K

    2011-10-01

    There is strong evidence that early pubertal timing is associated with adolescent problem behaviors. However, there has been limited investigation of the mechanisms or developmental relationships. The present study examined longitudinal models incorporating pubertal timing, delinquency, and sexual activity in a sample of 454 adolescents (9-13 years old at enrollment; 47% females). Participants were seen for three assessments approximately 1 year apart. Characteristics of friendship networks (older friends, male friends, older male friends) were examined as mediators. Structural equation modeling was used to test these associations as well as temporal relationships between sexual activity and delinquency. Results showed that early pubertal timing at Time 1 was related to more sexual activity at Time 2, which was related to higher delinquency at Time 3, a trend mediation effect. None of the friendship variables mediated these associations. Gender or maltreatment status did not moderate the meditational pathways. The results also supported the temporal sequence of sexual activity preceding increases in delinquency. These findings reveal that early maturing adolescents may actively seek out opportunities to engage in sexual activity which appears to be risk for subsequent delinquency. PMID:21191640

  8. Effects of early life stress on brain activity: implications from maternal separation model in rodents.

    PubMed

    Nishi, Mayumi; Horii-Hayashi, Noriko; Sasagawa, Takayo; Matsunaga, Wataru

    2013-01-15

    Adverse experiences in early life can affect the formation of neuronal circuits during postnatal development and exert long-lasting influences on neural function. Many studies have shown that daily repeated maternal separation (RMS), an animal model of early life stress, can modulate the hypothalamic-pituitary-adrenal axis (HPA-axis) and can affect subsequent brain function and emotional behavior during adulthood. However, the molecular basis of the long-lasting effects of early life stress on brain function has not been completely elucidated. In this mini-review, we introduce various cases of maternal separation in rodents and illustrate the alterations in HPA-axis activity by focusing on corticosterone (CORT), an end-product of the HPA-axis in rodents. We then present the characterization of the brain regions affected by various patterns of MS, including RMS and single time maternal separation (SMS) at various stages before weaning, by investigating c-Fos expression, a biological marker of neuronal activity. These CORT and c-Fos studies suggest that repeated early life stress may affect neuronal function in region- and temporal-specific manners, indicating a critical period for habituation to early life stress. Furthermore, we introduce changes in behavioral aspects and gene expression in adult mice exposed to RMS.

  9. Contrasting early visual cortical activation states causally involved in visual imagery and short-term memory.

    PubMed

    Cattaneo, Zaira; Vecchi, Tomaso; Pascual-Leone, Alvaro; Silvanto, Juha

    2009-10-01

    Whether visual imagery and visual short-term memory (STM) share the same neural resources, and the extent to which the early visual cortex (V1/V2) is involved in these processes, has been the subject of much debate. Here, we used transcranial magnetic stimulation (TMS) in two separate experiments to contrast the neural states associated with visual imagery and visual STM in the early visual cortex. In Experiment 1, we investigated V1/V2 activation states at the end of the retention phase in a visual imagery and a visual STM task. V1/V2 TMS facilitated performance in both tasks; the finding that imagery and STM interacted with TMS in the same way suggests that the two processes have similar effects on early visual cortical excitability. In Experiment 2, we investigated V1/V2 activation states at the beginning of the retention phase. V1/V2 TMS impaired performance in the visual STM task, whereas it had no effect on the imagery task. Taken together, our findings show that the late phases of the early visual cortical activation state associated with visual imagery and visual STM are similar; differences between the two processes are apparent in the early phases of the tasks. Our results also suggest that the causal role of the early visual cortex in visual STM includes both the initial translation of the visual input into working memory and the subsequent maintenance of the mental representation. Finally, our findings indicate that visual STM sensory recruitment in working memory might act via excitability modulation of V1/V2 neurons.

  10. Benzo[a]pyrene-induced cell cycle progression occurs via ERK-induced Chk1 pathway activation in human lung cancer cells.

    PubMed

    Wang, Bing-Yen; Wu, Sung-Yu; Tang, Sheau-Chung; Lai, Chien-Hung; Ou, Chu-Chyn; Wu, Ming-Fang; Hsiao, Yi-Min; Ko, Jiunn-Liang

    2015-03-01

    Benzo[a]pyrene (B[a]P) is a potent lung carcinogen derived from tobacco smoking and environmental contamination. This study aimed to investigate the signal transduction pathway responsible for B[a]P-induced non-small cell lung cancer (NSCLC) development. We exposed the human NSCLC cell lines Calu-1, CL3, H1299, CH27, H23, and H1355 to B[a]P and assessed cell cycle progression using flow cytometry. Expression of cell cycle mediators was measured using Western blot analyses and electrophoretic mobility shift assays (EMSAs). B[a]P exposure dramatically induced S-phase accumulation in H1355 cells. Phospho-p53 (Ser15 and Ser20), phospho-ERK, phospho-p38, and Bax were significantly increased in H1355 cells whereas phospho-Rb was decreased in these cells. In addition, B[a]P induced phosphorylation of checkpoint kinase-1 (Chk1) but not Chk2. EMSA experiments revealed a slower migrating band after c-Myc bound the E-box in response to B[a]P treatment, which was abolished upon the addition of the ERK inhibitor PD98059 in H1355 cells. Phospho-ERK inhibition and dominant negative mutant Chk1 expression reversed B[a]P-induced S phase accumulation and downregulated phospho-Chk1 and phospho-ERK expression. Taken together, these results suggest that activation of ERK and its downstream mediator Chk1 may contribute to B[a]P-induced S phase accumulation in H1355 cells. The results could help in the development of lung cancer treatments that target the Chk1 pathway through ERK.

  11. A Comparative Oncology Study of Iniparib Defines Its Pharmacokinetic Profile and Biological Activity in a Naturally-Occurring Canine Cancer Model.

    PubMed

    Saba, Corey; Paoloni, Melissa; Mazcko, Christina; Kisseberth, William; Burton, Jenna H; Smith, Annette; Wilson-Robles, Heather; Allstadt, Sara; Vail, David; Henry, Carolyn; Lana, Susan; Ehrhart, E J; Charles, Brad; Kent, Michael; Lawrence, Jessica; Burgess, Kristine; Borgatti, Antonella; Suter, Steve; Woods, Paul; Gordon, Ira; Vrignaud, Patricia; Khanna, Chand; LeBlanc, Amy K

    2016-01-01

    Development of iniparib as an anti-cancer agent was hindered in part by lingering questions regarding its mechanism of action, the activity of its metabolites, and their potential accumulation in tumors. Due to strong similarities in metabolism of iniparib between humans and dogs, a veterinary clinical trial in pet dogs with spontaneous cancers was designed to answer specific questions pertaining to pharmacokinetic exposures and tolerability of iniparib. Dogs were treated with iniparib alone and in combination with carboplatin chemotherapy. Iniparib doses ranged between 10-70 mg/kg intravenously (IV). Plasma, tumor and normal tissue samples were collected before and at various time points scheduled after exposure for pharmacokinetic and biologic analysis. The primary endpoints included characterization of dose-limiting toxicities (DLT) and determination of the drug exposures that could be achieved in both normal and tumor tissues. Nineteen dogs were treated. DLT included fever, anorexia, diarrhea, neutropenia, and thrombocytopenia; most effects were attributable to carboplatin based on the timing of adverse event onset. The maximum tolerated dose (MTD) of iniparib was not identified. Moderate to high variability in plasma exposure was noted for iniparib and all metabolites between animals. When quantifiable, iniparib and metabolite plasma:tumor ratios were < 0.088 and <1.7, respectively. In this study, iniparib was well tolerated as a single agent and in combination with carboplatin over a range of doses. However, clinically relevant concentrations of the parent drug and selected metabolites were not detectable in canine tumor tissues at any studied dose, thus eliminating expectations for clinical responses in dogs or humans. Negative clinical trials in humans, and the uncertainties of its mechanism of action, ultimately led to the decision to stop clinical development of the drug. Nevertheless, the questions that can be asked and answered within the comparative

  12. A Comparative Oncology Study of Iniparib Defines Its Pharmacokinetic Profile and Biological Activity in a Naturally-Occurring Canine Cancer Model

    PubMed Central

    Saba, Corey; Paoloni, Melissa; Mazcko, Christina; Kisseberth, William; Burton, Jenna H.; Smith, Annette; Wilson-Robles, Heather; Allstadt, Sara; Vail, David; Henry, Carolyn; Lana, Susan; Ehrhart, E. J.; Charles, Brad; Kent, Michael; Lawrence, Jessica; Burgess, Kristine; Borgatti, Antonella; Suter, Steve; Woods, Paul; Gordon, Ira; Vrignaud, Patricia; Khanna, Chand; LeBlanc, Amy K.

    2016-01-01

    Development of iniparib as an anti-cancer agent was hindered in part by lingering questions regarding its mechanism of action, the activity of its metabolites, and their potential accumulation in tumors. Due to strong similarities in metabolism of iniparib between humans and dogs, a veterinary clinical trial in pet dogs with spontaneous cancers was designed to answer specific questions pertaining to pharmacokinetic exposures and tolerability of iniparib. Dogs were treated with iniparib alone and in combination with carboplatin chemotherapy. Iniparib doses ranged between 10–70 mg/kg intravenously (IV). Plasma, tumor and normal tissue samples were collected before and at various time points scheduled after exposure for pharmacokinetic and biologic analysis. The primary endpoints included characterization of dose-limiting toxicities (DLT) and determination of the drug exposures that could be achieved in both normal and tumor tissues. Nineteen dogs were treated. DLT included fever, anorexia, diarrhea, neutropenia, and thrombocytopenia; most effects were attributable to carboplatin based on the timing of adverse event onset. The maximum tolerated dose (MTD) of iniparib was not identified. Moderate to high variability in plasma exposure was noted for iniparib and all metabolites between animals. When quantifiable, iniparib and metabolite plasma:tumor ratios were < 0.088 and <1.7, respectively. In this study, iniparib was well tolerated as a single agent and in combination with carboplatin over a range of doses. However, clinically relevant concentrations of the parent drug and selected metabolites were not detectable in canine tumor tissues at any studied dose, thus eliminating expectations for clinical responses in dogs or humans. Negative clinical trials in humans, and the uncertainties of its mechanism of action, ultimately led to the decision to stop clinical development of the drug. Nevertheless, the questions that can be asked and answered within the comparative

  13. Early Sexual Intercourse: Prospective Associations with Adolescents Physical Activity and Screen Time

    PubMed Central

    Wijtzes, Anne; van de Bongardt, Daphne; van de Looij-Jansen, Petra; Bannink, Rienke; Raat, Hein

    2016-01-01

    Objectives To assess the prospective associations of physical activity behaviors and screen time with early sexual intercourse initiation (i.e., before 15 years) in a large sample of adolescents. Methods We used two waves of data from the Rotterdam Youth Monitor, a longitudinal study conducted in the Netherlands. The analysis sample consisted of 2,141 adolescents aged 12 to 14 years (mean age at baseline = 12.2 years, SD = 0.43). Physical activity (e.g., sports outside school), screen time (e.g., computer use), and early sexual intercourse initiation were assessed by means of self-report questionnaires. Logistic regression models were tested to assess the associations of physical activity behaviors and screen time (separately and simultaneously) with early sexual intercourse initiation, controlling for confounders (i.e., socio-demographics and substance use). Interaction effects with gender were tested to assess whether these associations differed significantly between boys and girls. Results The only physical activity behavior that was a significant predictor of early sexual intercourse initiation was sports club membership. Adolescent boys and girls who were members of a sports club) were more likely to have had early sex (OR = 2.17; 95% CI = 1.33, 3.56. Significant gender interaction effects indicated that boys who watched TV ≥2 hours/day (OR = 2.00; 95% CI = 1.08, 3.68) and girls who used the computer ≥2 hours/day (OR = 3.92; 95% CI = 1.76, 8.69) were also significantly more likely to have engaged in early sex. Conclusion These findings have implications for professionals in general pediatric healthcare, sexual health educators, policy makers, and parents, who should be aware of these possible prospective links between sports club membership, TV watching (for boys), and computer use (for girls), and early sexual intercourse initiation. However, continued research on determinants of adolescents’ early sexual initiation is needed to further contribute to

  14. Multi-component Magnetization Of The Late Pliocene Pyroclastic Flow Deposit In Central Japan, Indicating Early Early Pleistocene Fault Activity

    NASA Astrophysics Data System (ADS)

    Ueki, T.; Yamazaki, T.; Funaki, M.; Hoshi, H.

    2003-12-01

    acquired normal magnetization components by hydrothermal alternation in the Olduvai Subchron; low and high temperature components are secondary TRM by re-heating for titanomagnetites and CRM by formation of magnetite, respectively. Positive fold test for secondary magnetization of the welded tuff bed would introduce the early Early Pleistocene activity of the Otari-Nakayama fault.

  15. Involvement of human internal globus pallidus in the early modulation of cortical error-related activity.

    PubMed

    Herrojo Ruiz, María; Huebl, Julius; Schönecker, Thomas; Kupsch, Andreas; Yarrow, Kielan; Krauss, Joachim K; Schneider, Gerd-Helge; Kühn, Andrea A

    2014-06-01

    The detection and assessment of errors are a prerequisite to adapt behavior and improve future performance. Error monitoring is afforded by the interplay between cortical and subcortical neural systems. Ample evidence has pointed to a specific cortical error-related evoked potential, the error-related negativity (ERN), during the detection and evaluation of response errors. Recent models of reinforcement learning implicate the basal ganglia (BG) in early error detection following the learning of stimulus-response associations and in the modulation of the cortical ERN. To investigate the influence of the human BG motor output activity on the cortical ERN during response errors, we recorded local field potentials from the sensorimotor area of the internal globus pallidus and scalp electroencephalogram representing activity from the posterior medial frontal cortex in patients with idiopathic dystonia (hands not affected) during a flanker task. In error trials, a specific pallidal error-related potential arose 60 ms prior to the cortical ERN. The error-related changes in pallidal activity-characterized by theta oscillations-were predictive of the cortical error-related activity as assessed by Granger causality analysis. Our findings show an early modulation of error-related activity in the human pallidum, suggesting that pallidal output influences the cortex at an early stage of error detection.

  16. The Early Inbound Activity of Comet ISON (C/2012 S1)

    NASA Astrophysics Data System (ADS)

    A'Hearn, Michael F.; Biver, N.; Bodewits, D.; Farnham, T. L.; Feaga, L. M.; Feldman, P. D.; Knight, M. M.; O'Rourke, L.; Schleicher, D. G.; Weaver, H. A.

    2013-10-01

    We have assembled a variety of data on the early behavior of comet ISON through early June 2013, including V magnitudes from the ground and from spacecraft (SWIFT, DIFlyby), upper limits on gas from the DIFlyby, Herschel, and Hubble, and ground-based detections of CO and CN. We argue that the comet’s activity was steadily increasing from the pre-discovery observations in 2011 through late 2012. The activity then flattened and remained constant until January 2013, at which point it started to decrease and continued decreasing until earliest June. We interpret this in the classical picture (e.g., Whipple 1978 Moon and Planets 18, 343) of a dynamically new comet from the Oort cloud having a totally irradiated crust of order 3-10 meters thick from 4.5 billion years of galactic cosmic rays outside the heliosphere. The irradiated layer is released at very large distances due to the presence of free radicals and other chemically active species. As this crust is depleted the activity decreases and in early June we are awaiting the onset of “normal” cometary activity, which should be detected by fall at the latest.

  17. Home activities of Mexican American children: structuring early socialization and cognitive engagement.

    PubMed

    Bridges, Margaret; Cohen, Shana R; Scott, Lyn; Fuller, Bruce; Anguiano, Rebecca; Figueroa, Ariana Mangual; Livas-Dlott, Alejandra

    2015-04-01

    The question of how home activities advance the early social and cognitive development of Latino children receives growing attention from psychologists and social scientists. Some scholars and practitioners, focused on promoting "school readiness," frame the problem as weak parenting, signaled by insufficient rich language or academic skills. Other theorists, rooted in ecocultural theory, argue that early socialization and cognitive engagement are culturally situated within routine home activities. These activity structures vary and change over time as families acculturate, adapting to local social ecologies. Little is known empirically about the activity structures within Latino homes, including how young children participate. We detail the social architecture and cognitive engagement pertaining to 6 prevalent home activities in which 24 Mexican American 4-year-olds were engaged over 14 months. We then report how children participate in these 6 activities, and their potential relevance to the cognitive skills gap seen at school entry. We found that children's activities reproduced heritage language, symbols, and knowledge less often than suggested in prior literature; children's typical level of cognitive engagement varied greatly among tasks; and the distribution of time spent in activities is associated with the mother's school attainment and home language. PMID:25364833

  18. Home activities of Mexican American children: structuring early socialization and cognitive engagement.

    PubMed

    Bridges, Margaret; Cohen, Shana R; Scott, Lyn; Fuller, Bruce; Anguiano, Rebecca; Figueroa, Ariana Mangual; Livas-Dlott, Alejandra

    2015-04-01

    The question of how home activities advance the early social and cognitive development of Latino children receives growing attention from psychologists and social scientists. Some scholars and practitioners, focused on promoting "school readiness," frame the problem as weak parenting, signaled by insufficient rich language or academic skills. Other theorists, rooted in ecocultural theory, argue that early socialization and cognitive engagement are culturally situated within routine home activities. These activity structures vary and change over time as families acculturate, adapting to local social ecologies. Little is known empirically about the activity structures within Latino homes, including how young children participate. We detail the social architecture and cognitive engagement pertaining to 6 prevalent home activities in which 24 Mexican American 4-year-olds were engaged over 14 months. We then report how children participate in these 6 activities, and their potential relevance to the cognitive skills gap seen at school entry. We found that children's activities reproduced heritage language, symbols, and knowledge less often than suggested in prior literature; children's typical level of cognitive engagement varied greatly among tasks; and the distribution of time spent in activities is associated with the mother's school attainment and home language.

  19. Histone Deacetylase Inhibitors Activate Tristetraprolin Expression through Induction of Early Growth Response Protein 1 (EGR1) in Colorectal Cancer Cells

    PubMed Central

    Sobolewski, Cyril; Sanduja, Sandhya; Blanco, Fernando F.; Hu, Liangyan; Dixon, Dan A.

    2015-01-01

    The RNA-binding protein tristetraprolin (TTP) promotes rapid decay of mRNAs bearing 3' UTR AU-rich elements (ARE). In many cancer types, loss of TTP expression is observed allowing for stabilization of ARE-mRNAs and their pathologic overexpression. Here we demonstrate that histone deacetylase (HDAC) inhibitors (Trichostatin A, SAHA and sodium butyrate) promote TTP expression in colorectal cancer cells (HCA-7, HCT-116, Moser and SW480 cells) and cervix carcinoma cells (HeLa). We found that HDAC inhibitors-induced TTP expression, promote the decay of COX-2 mRNA, and inhibit cancer cell proliferation. HDAC inhibitors were found to promote TTP transcription through activation of the transcription factor Early Growth Response protein 1 (EGR1). Altogether, our findings indicate that loss of TTP in tumors occurs through silencing of EGR1 and suggests a therapeutic approach to rescue TTP expression in colorectal cancer. PMID:26343742

  20. Respiratory constraints during activities in daily life and the impact on health status in patients with early-stage COPD: a cross-sectional study

    PubMed Central

    van Helvoort, Hanneke AC; Willems, Laura M; Dekhuijzen, PN Richard; van Hees, Hieronymus WH; Heijdra, Yvonne F

    2016-01-01

    In patients with chronic obstructive pulmonary disease (COPD), exercise capacity is reduced, resulting over time in physical inactivity and worsened health status. It is unknown whether ventilatory constraints occur during activities of daily life (ADL) in early stages of COPD. The aim of this study was to assess respiratory mechanics during ADL and to study its consequences on dyspnoea, physical activity and health status in early-stage COPD compared with healthy controls. In this cross-sectional study, 39 early-stage COPD patients (mean FEV1 88±s.d. 12% predicted) and 20 controls performed 3 ADL: climbing stairs, vacuum cleaning and displacing groceries in a cupboard. Respiratory mechanics were measured during ADL. Physical activity was measured with accelerometry. Health status was assessed by the Nijmegen Clinical Screening Instrument. Compared with controls, COPD patients had greater ventilatory inefficiency and higher ventilatory requirements during ADL (P<0.05). Dyspnoea scores were increased in COPD compared with controls (P<0.001). During ADL, >50% of the patients developed dynamic hyperinflation in contrast to 10–35% of the controls. Higher dyspnoea was scored by patients with dynamic hyperinflation. Physical activity was low but comparable between both groups. From the patients, 55–84% experienced mild-to-severe problems in health status compared with 5–25% of the controls. Significant ventilatory constraints already occur in early-stage COPD patients during common ADL and result in increased dyspnoea. Physical activity level is not yet reduced, but many patients already experience limitations in health status. These findings reinforce the importance of early diagnosis of COPD and assessment of more than just spirometry. PMID:27734959

  1. Sources of Continuity and Change in Activity Level in Early Childhood

    PubMed Central

    Saudino, Kimberly J.

    2011-01-01

    Actigraphs and parent and observer ratings were used to explore genetic influences on continuity and change in activity level (AL) in early childhood. Over 300 pairs of twins wore actigraphs for a 48-hour period in the home and laboratory at ages 2 and 3. AL was genetically influenced at both ages with little evidence of differential heritability across age. For all measures, genetic influences contributed to phenotypic continuity. With the exception of the actigraph measure of AL in the home, new genetic effects emerged at age 3 indicating that genetic factors influence both continuity and change in AL in early childhood. Nonshared environmental influences were also a source of change in AL across the transition from infancy to early childhood. PMID:22103336

  2. MAP kinase activity increases during mitosis in early sea urchin embryos.

    PubMed

    Philipova, R; Whitaker, M

    1998-09-01

    A MBP kinase activity increases at mitosis during the first two embryonic cell cycles of the sea urchin embryo. The activity profile of the MBP kinase is the same both in whole cell extracts and after immunoprecipitation with an anti-MAP kinase antibody (2199). An in-gel assay of MBP activity also shows the same activity profile. The activity is associated with the 44 kDa protein that cross-reacts with anti-MAP kinase antibodies. The 44 kDa protein shows cross-reactivity to anti-phosphotyrosine and MAP kinase-directed anti-phosphotyrosine/phosphothreonine antibodies at the times that MBP kinase activity is high. The 2199 antibody co-precipitates some histone H1 kinase activity, but the MBP kinase activity cannot be accounted for by histone H1 kinase-dependent phosphorylation of MBP. The MAP kinase 2199 antibody was used to purify the MBP kinase activity. Peptide sequencing after partial digestion shows the protein to be homologous to MAP kinases from other species. These data demonstrate that MAP kinase activation during nuclear division is not confined to meiosis, but also occurs during mitotic cell cycles. MAP kinase activity in immunoprecipitates also increases immediately after fertilization, which in the sea urchin egg occurs at interphase of the cell cycle. Treating unfertilized eggs with the calcium ionophore A23187 stimulates the increase in MAP kinase activity, demonstrating that a calcium signal can activate MAP kinase and suggesting that the activation of MAP kinase at fertilization is due to the fertilization-induced increase in cytoplasmic free calcium concentration. This signalling pathway must differ from the pathway responsible for calcium-induced inactivation of MAP kinase activity that is found in eggs that are fertilized in meiotic metaphase. PMID:9701549

  3. A Spatio-Pedagogical Approach to Symbolic Play as Kindergarten Activity in Early Childhood.

    ERIC Educational Resources Information Center

    Michalopoulou, Aikaterini

    2001-01-01

    Studied the symbolic play that occurs in activity corners set up around toy-objects in Greek kindergartens. Found notable differences in levels of symbolism and complexity of the play. Concluded that the most favored groups were those in which: (1) classroom space was polyvalent, permitting its informal re-organization; and (2) the teacher was an…

  4. Use of green fluorescent fusion protein to track activation of the transcription factor osterix during early osteoblast differentiation

    SciTech Connect

    Tai Guangping; Christodoulou, Ioannis; Bishop, Anne E.; Polak, Julia M. . E-mail: julia.polak@imperial.ac.uk

    2005-08-12

    Osterix (Osx) is a transcription factor required for the differentiation of preosteoblasts into fully functioning osteoblasts. However, the pattern of Osx activation during preosteoblast differentiation and maturation has not been clearly defined. Our aim was to study Osx activation during these processes in osteoblasts differentiating from murine and human embryonic stem cells (ESC). To do this, we constructed an Osx-GFP fusion protein reporter system to track Osx translocation within the cells. The distribution of Osx-GFP at representative stages of differentiation was also investigated by screening primary osteoblasts, mesenchymal stem cells, synoviocytes, and pre-adipocytes. Our experiments revealed that Osx-GFP protein was detectable in the cytoplasm of cultured, differentiated ESC 4 days after plating of enzymatically dispersed embryoid bodies. Osterix-GFP protein became translocated into the nucleus on day 7 following transfer of differentiated ESC to osteogenic medium. After 14 days of differentiation, cells showing nuclear translocation of Osx-GFP formed rudimentary bone nodules that continued to increase in number over the following weeks (through day 21). We also found that Osx translocated into the nuclei of mesenchymal stem cells (C3H10T1/2) and pre-osteoblasts (MC3T3-E1) and showed partial activation in pre-adipocytes (MC3T3-L1). These data suggest that Osx activation occurs at a very early point in the differentiation of the mesenchymal-osteoblastic lineage.

  5. Inhibition of Microglia Activation as a Phenotypic Assay in Early Drug Discovery

    PubMed Central

    Figuera-Losada, Mariana; Rojas, Camilo; Slusher, Barbara S.

    2014-01-01

    Complex biological processes such as inflammation, cell death, migration, proliferation, and the release of biologically active molecules can be used as outcomes in phenotypic assays during early stages of drug discovery. Although target-based approaches have been widely used over the past decades, a disproportionate number of first-in-class drugs have been identified using phenotypic screening. This review details phenotypic assays based on inhibition of microglial activation and their utility in primary and secondary screening, target validation, and pathway elucidation. The role of microglia, both in normal as well as in pathological conditions such as chronic neurodegenerative diseases, is reviewed. Methodologies to assess microglia activation in vitro are discussed in detail, and classes of therapeutic drugs known to decrease the proinflammatory and cytotoxic responses of activated microglia are appraised, including inhibitors of glutaminase, cystine/glutamate antiporter, nuclear factor κB, and mitogen-activated protein kinases. PMID:23945875

  6. Platelet Mitochondrial Activity and Pesticide Exposure in Early Parkinson’s Disease

    PubMed Central

    Bronstein, Jeff M.; Paul, Kimberly; Yang, Laurice; Haas, Richard H.; Shults, Clifford W.; Le, Thuy; Ritz, Beate

    2015-01-01

    Background Mitochondrial dysfunction has been implicated in the pathogenesis of Parkinson’s disease (PD) but the cause of this dysfunction is unclear. Methods Platelet mitochondrial complex I and I/III (NADH cytochrome c reductase, NCCR) activities were measured in early PD patients and matched controls enrolled in a population based case-control study. Ambient agricultural pesticide exposures were assessed with a geographic information system and California Pesticide Use Registry. Results In contrast to some previous reports, we found no differences in complex I and I/III activities in subjects with PD and controls. We did find that NCCR activity correlated with subjects’ exposure to pesticides known to inhibit mitochondrial activity regardless of their diagnosis. Conclusions ETC activity is not altered in PD in this well-characterized cohort when compared to community-matched controls but appears to be affected by environmental toxins, such as mitochondria-inhibiting pesticides. PMID:25757798

  7. Aurora A drives early signalling and vesicle dynamics during T-cell activation

    PubMed Central

    Blas-Rus, Noelia; Bustos-Morán, Eugenio; Pérez de Castro, Ignacio; de Cárcer, Guillermo; Borroto, Aldo; Camafeita, Emilio; Jorge, Inmaculada; Vázquez, Jesús; Alarcón, Balbino; Malumbres, Marcos; Martín-Cófreces, Noa B.; Sánchez-Madrid, Francisco

    2016-01-01

    Aurora A is a serine/threonine kinase that contributes to the progression of mitosis by inducing microtubule nucleation. Here we have identified an unexpected role for Aurora A kinase in antigen-driven T-cell activation. We find that Aurora A is phosphorylated at the immunological synapse (IS) during TCR-driven cell contact. Inhibition of Aurora A with pharmacological agents or genetic deletion in human or mouse T cells severely disrupts the dynamics of microtubules and CD3ζ-bearing vesicles at the IS. The absence of Aurora A activity also impairs the activation of early signalling molecules downstream of the TCR and the expression of IL-2, CD25 and CD69. Aurora A inhibition causes delocalized clustering of Lck at the IS and decreases phosphorylation levels of tyrosine kinase Lck, thus indicating Aurora A is required for maintaining Lck active. These findings implicate Aurora A in the propagation of the TCR activation signal. PMID:27091106

  8. I Am Your Child/Early Childhood Public Engagement Campaign. Report on Local, State and National Organization Activities.

    ERIC Educational Resources Information Center

    Families and Work Inst., New York, NY.

    Comprised of two reports, this publication summarizes the activities of state and local coalitions and national organizations in the I Am Your Child Early Childhood Public Engagement Campaign, an effort to increase public awareness of the importance of the early childhood stage of development. The first report summarizes activities and…

  9. Early (M170) activation of face-specific cortex by face-like objects.

    PubMed

    Hadjikhani, Nouchine; Kveraga, Kestutis; Naik, Paulami; Ahlfors, Seppo P

    2009-03-01

    The tendency to perceive faces in random patterns exhibiting configural properties of faces is an example of pareidolia. Perception of 'real' faces has been associated with a cortical response signal arising at approximately 170 ms after stimulus onset, but what happens when nonface objects are perceived as faces? Using magnetoencephalography, we found that objects incidentally perceived as faces evoked an early (165 ms) activation in the ventral fusiform cortex, at a time and location similar to that evoked by faces, whereas common objects did not evoke such activation. An earlier peak at 130 ms was also seen for images of real faces only. Our findings suggest that face perception evoked by face-like objects is a relatively early process, and not a late reinterpretation cognitive phenomenon.

  10. Early (N170) activation of face-specific cortex by face-like objects

    PubMed Central

    Hadjikhani, Nouchine; Kveraga, Kestutis; Naik, Paulami; Ahlfors, Seppo P.

    2009-01-01

    The tendency to perceive faces in random patterns exhibiting configural properties of faces is an example of pareidolia. Perception of ‘real’ faces has been associated with a cortical response signal arising at about 170ms after stimulus onset; but what happens when non-face objects are perceived as faces? Using magnetoencephalography (MEG), we found that objects incidentally perceived as faces evoked an early (165ms) activation in the ventral fusiform cortex, at a time and location similar to that evoked by faces, whereas common objects did not evoke such activation. An earlier peak at 130 ms was also seen for images of real faces only. Our findings suggest that face perception evoked by face-like objects is a relatively early process, and not a late re-interpretation cognitive phenomenon. PMID:19218867

  11. Adventitial fibroblasts are activated in the early stages of atherosclerosis in the apolipoprotein E knockout mouse

    SciTech Connect

    Xu Fang; Ji Jian; Li Li; Chen Rong; Hu Weicheng . E-mail: huweicheng@sdu.edu.cn

    2007-01-19

    The role of the adventitia in vascular function and vascular lesion formation has been largely ignored. This study observed the activation of the adventitia and specifically the fibroblasts in the development of atherosclerosis in the apoE(-/-) mouse. The results showed a gradual increase in expression of collagen types I and III after 2, 4, and 8 weeks of hyperlipidic diet. The earliest expression of monocyte chemoattractant protein-1 (MCP-1) protein and mRNA was detected in the adventitial fibroblast before the formation of intimal lesions. Proliferation, too, was first found in the adventitial fibroblasts. We hypothesize that the adventitial fibroblast is activated in the early stage of atherosclerosis. Adventitial inflammation may be an early event in the development of atherosclerotic lesions.

  12. Early psychosis, activity performance and social participation: a conceptual model to guide rehabilitation and recovery.

    PubMed

    Woodside, Harriet; Krupa, Terry; Pocock, Karen

    2007-01-01

    In this paper we present a conceptual model focusing on activity performance and social participation of individuals in the period prior to their first acute episodes of psychosis. The model was developed using the constructivist grounded theory method. Data from interviews and documents was collected from 25 primary participants. Interviews were also conducted with 15 members of the participants' support networks and six experts in the field of early psychosis and rehabilitation. The model illustrates how the core constructs of activity performance and social participation are set against the natural context and influenced by shifts in three determinants: faltering personal capacities, negotiating for success and risk factors. The model suggests rehabilitation and recovery practices in early intervention work. PMID:18018956

  13. Early Detection of Volcanic Eruptions Using Lightning Activity in South America

    NASA Astrophysics Data System (ADS)

    Nicora, M. G.; Bürgesser, R. E.; Quel, E. J.; Avila, E.

    2013-05-01

    A study of the lightning activity produced by the eruption of the Cordón Caulle volcano during June 2011 was performed by using the World Wide Lightning Location Network data. The observed lightning activity corresponds to the electrical activity of the volcanic plume with a good correlation between the amount of lightning detected and the volcanic plume height. Although the detected lightning activity was low, the results agree with previous studies and show that lightning activity could be use as a proxy of the volcanic activity. This study also shows the feasibility on the use of the network for early detection of volcanic eruptions. The Global Volcanic Lightning Monitor is an experimental research project, based on the World Wide Lightning Location Network data, which sent an alert of the eruption of the Cordón Caulle volcanic complex before the report of the National Service of Geology and Mining (SERNAGEOMIN) of Chile. This demonstrate the relevance of the system as support of national warning systems (if any) and, where there are no continuous monitoring of eruptive systems, as early warning of volcanic eruptions.

  14. Inhibition of Rac1 GTPase activity affects porcine oocyte maturation and early embryo development

    PubMed Central

    Song, Si-Jing; Wang, Qiao-Chu; Jia, Ru-Xia; Cui, Xiang-Shun; Kim, Nam-Hyung; Sun, Shao-Chen

    2016-01-01

    Mammalian oocyte asymmetric division relies on the eccentric positioning of the spindle, resulting in the polar body formation. Small signaling G protein Rac1 is a member of GTPases, which regulates a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases. However, effects of Rac1 on the porcine oocyte maturation and early embryo development are not fully understood. In present study we investigated the role of Rac1 in oocyte maturation and embryo cleavage. We first found that Rac1 localized at the cortex of the porcine oocytes, and disrupting the Rac1 activities by treating with NSC 23766 led to the failure of polar body emission. In addition, a majority of treated oocytes exhibited abnormal spindle morphology, indicating that Rac1 may involve into porcine oocyte spindle formation. This might be due to the regulation of Rac1 on MAPK, since p-MAPK expression decreased after NSC 23766 treatments. Moreover, we found that the position of most meiotic spindles in treated oocytes were away from the cortex, indicating the roles of Rac1 on meiotic spindle positioning. Our results also showed that inhibition of Rac1 activity caused the failure of early embryo development. Therefore, our study showed the critical roles of Rac1 GTPase on porcine oocyte maturation and early embryo cleavage. PMID:27694954

  15. Rapid Temperature Changes and the Early Activity on Comet 67P/Churyumov-Gerasimenko

    NASA Astrophysics Data System (ADS)

    Alí-Lagoa, V.; Delbo', M.; Libourel, G.

    2015-09-01

    The so-called “early activity” of comet 67P/Churyumov-Gerasimenko has been observed to originate mostly in parts of the concave region or “neck” between its two lobes. Since activity is driven by the sublimation of volatiles, this is a puzzling result because this area is less exposed to the Sun and is therefore expected to be cooler on average. We used a thermophysical model that takes into account thermal inertia, global self-heating, and shadowing, to compute surface temperatures of the comet. We found that, for every rotation in the 2014 August-December period, some parts of the neck region undergo the fastest temperature variations of the comet’s surface precisely because they are shadowed by their surrounding terrains. Our work suggests that these fast temperature changes are correlated to the early activity of the comet, and we put forward the hypothesis that erosion related to thermal cracking is operating at a high rate on the neck region due to these rapid temperature variations. This may explain why the neck contains some ice—as opposed to most other parts of the surface—and why it is the main source of the comet’s early activity. In a broader context, these results indicate that thermal cracking can operate faster on atmosphereless bodies with significant concavities than implied by currently available estimates.

  16. Magnetoencephalography reveals early activation of V4 in grapheme-color synesthesia.

    PubMed

    Brang, D; Hubbard, E M; Coulson, S; Huang, M; Ramachandran, V S

    2010-10-15

    Grapheme-color synesthesia is a neurological phenomenon in which letters and numbers (graphemes) consistently evoke particular colors (e.g. A may be experienced as red). The cross-activation theory proposes that synesthesia arises as a result of cross-activation between posterior temporal grapheme areas (PTGA) and color processing area V4, while the disinhibited feedback theory proposes that synesthesia arises from disinhibition of pre-existing feedback connections. Here we used magnetoencephalography (MEG) to test whether V4 and PTGA activate nearly simultaneously, as predicted by the cross-activation theory, or whether V4 activation occurs only after the initial stages of grapheme processing, as predicted by the disinhibited feedback theory. Using our high-resolution MEG source imaging technique (VESTAL), PTGA and V4 regions of interest (ROIs) were separately defined, and activity in response to the presentation of achromatic graphemes was measured. Activation levels in PTGA did not significantly differ between synesthetes and controls (suggesting similar grapheme processing mechanisms), whereas activation in V4 was significantly greater in synesthetes. In synesthetes, PTGA activation exceeded baseline levels beginning 105-109ms, and V4 activation did so 5ms later, suggesting nearly simultaneous activation of these areas. Results are discussed in the context of an updated version of the cross-activation model, the cascaded cross-tuning model of grapheme-color synesthesia.

  17. Neuroendocrine activation and markers of early reperfusion in the acute phase of myocardial infarction.

    PubMed

    Ray, S G; Morton, J J; Dargie, H J

    1993-12-01

    Potentially harmful stimulation of the neuroendocrine axis occurs in the early hours of myocardial infarction. It has been suggested that this acute neuroendocrine response might be attenuated by early therapeutic reperfusion. To test this hypothesis we measured plasma concentrations of atrial natriuretic factor (ANF), renin, adrenaline (ADR) and noradrenaline (NADR) on admission and at 1 h and 4 h in 32 patients undergoing streptokinase treatment within 6 h of myocardial infarction. Fractional changes (FC) in hormone levels were calculated: e.g. ANFO-ANF4/ANFO. Resolution of ST segment elevation at 4 h was the primary measure of reperfusion. Sixteen patients showed ST segment resolution. There was no difference in hormone levels at baseline between reperfused and non-reperfused patients. Fractional changes in ANF, renin and ADR were similar in both groups. NADR fell from admission to 4 h in reperfused patients but rose in non-reperfused (FC 0.28 vs -0.10; P = 0.054). There was no difference in the changes in pulse rate or blood pressure from admission to 4 h between the two groups. Thus there is no evidence that early reperfusion acutely alters the release of ANF, renin or ADR to myocardial infarction. Although plasma NADR tended to fall acutely in reperfused patients this was not accompanied by other markers of sympathetic withdrawal.

  18. Effect of Tributyrin on Electrical Activity in the Small Intestine during Early Postoperative Period.

    PubMed

    Tropskaya, N S; Kislyakova, E A; Popova, T S

    2015-12-01

    The effect of enteral administration of tributyrin on electrical activity in the upper segments of the small intestine was examined in rats on the model of postoperative ileus. This postoperative state is characterized with pronounced and long-term disturbances in generation of migrating myoelectric complex of the small intestine. The enteral administration of tributyrin in the early postoperative period aimed to suppress the non-adrenergic non-cholinergic influences and activation of the cholinergic anti-inflammatory pathways is an effective procedure to normalize the migrating myoelectric complex and therefore the coordinated propulsive peristalsis in the small intestine.

  19. Heterosis manifestation during early Arabidopsis seedling development is characterized by intermediate gene expression and enhanced metabolic activity in the hybrids.

    PubMed

    Meyer, Rhonda C; Witucka-Wall, Hanna; Becher, Martina; Blacha, Anna; Boudichevskaia, Anastassia; Dörmann, Peter; Fiehn, Oliver; Friedel, Svetlana; von Korff, Maria; Lisec, Jan; Melzer, Michael; Repsilber, Dirk; Schmidt, Renate; Scholz, Matthias; Selbig, Joachim; Willmitzer, Lothar; Altmann, Thomas

    2012-08-01

    Heterosis-associated cellular and molecular processes were analyzed in seeds and seedlings of Arabidopsis thaliana accessions Col-0 and C24 and their heterotic hybrids. Microscopic examination revealed no advantages in terms of hybrid mature embryo organ sizes or cell numbers. Increased cotyledon sizes were detectable 4 days after sowing. Growth heterosis results from elevated cell sizes and numbers, and is well established at 10 days after sowing. The relative growth rates of hybrid seedlings were most enhanced between 3 and 4 days after sowing. Global metabolite profiling and targeted fatty acid analysis revealed maternal inheritance patterns for a large proportion of metabolites in the very early stages. During developmental progression, the distribution shifts to dominant, intermediate and heterotic patterns, with most changes occurring between 4 and 6 days after sowing. The highest incidence of heterotic patterns coincides with establishment of size differences at 4 days after sowing. In contrast, overall transcript patterns at 4, 6 and 10 days after sowing are characterized by intermediate to dominant patterns, with parental transcript levels showing the largest differences. Overall, the results suggest that, during early developmental stages, intermediate gene expression and higher metabolic activity in the hybrids compared to the parents lead to better resource efficiency, and therefore enhanced performance in the hybrids.

  20. Physical activity, sedentary behaviour and energy balance in the preschool child: opportunities for early obesity prevention.

    PubMed

    Reilly, John J

    2008-08-01

    Prevalence of obesity in preschool children has increased dramatically in recent years. The preschool years (age 3-6 years) have been regarded as critical for the programming of energy balance, via the concept of early 'adiposity rebound'. Children who undergo early adiposity rebound are at increased risk of later obesity. Recent evidence suggests that associations between timing of adiposity rebound and later obesity may not reflect programming, but might denote that 'obesogenic' growth trajectories are often established by the preschool period. Studies of objectively-measured physical activity and sedentary behaviour in preschool children show that levels of physical activity are typically low and sedentary behaviour high. The review of evidence presented here is supportive of the hypothesis that physical activity is protective against obesity in the preschool period, and that sedentary behaviour, particularly television viewing, is obesogenic. Definitive evidence on dose-response relationships between physical activity, sedentary behaviour and obesity remain unclear. Dose-response evidence could be obtained fairly readily by intervention and longitudinal observational studies that use accelerometry in preschool children. The generalisability of much of the evidence base is limited and there is a need for research on the influence of physical activity and sedentary behaviour in the preschool years in the aetiology of obesity in the developing world.

  1. Relationship between renal histology and plasma antithrombin III activity in women with early onset preeclampsia.

    PubMed

    Weiner, C P; Bonsib, S M

    1990-04-01

    Renal biopsy was performed in 12 women with the clinical diagnosis of severe, early-onset preeclampsia at the time of cesarean delivery for the express purpose of aiding future counseling on the risk of recurrence. The mean gestation at delivery was 30 +/- 3 weeks. The mean birthweight was 1090 +/- 505 gm. Four women (33%) were multiparous. Antithrombin III activity was determined immediately prior to delivery unrelated to clinical care and as part of other protocols. The biopsy was performed without difficulty in each, although the sample was inadequate in one patient. The clinical diagnosis of preeclampsia was confirmed in nine (82%). However, three of the nine had underlying renal disease, as did the two women without histologic evidence of preeclampsia (42% of the total). Correlations between laboratory parameters with the histopathologic diagnoses were sought. Neither uric acid, creatinine, blood urea nitrogen, platelet count, or 24-hour urinary protein measurements aided the differentiation of the various subgroups. Antithrombin III activity in women with biopsy-supported preeclampsia (77% +/- 12%) was significantly lower than that in women without histologic evidence of preeclampsia (116% +/- 8%). Antithrombin III activity correctly predicted biopsy findings in at least 9 of 11 (82%). These preliminary findings confirm the high frequency of underlying disease in women with early-onset preeclampsia. Although low antithrombin III activity does not differentiate between "pure" preeclampsia and superimposed disease, a normal antithrombin III activity is reassuring and more consistent with a nonpreeclamptic renal complication than with preeclampsia.

  2. Capitalizing on the Teachable Moment: Osteoarthritis Physical Activity and Exercise Net for Improving Physical Activity in Early Knee Osteoarthritis

    PubMed Central

    Lineker, Sydney; Cibere, Jolanda; Crooks, Valorie A; Jones, Catherine A; Kopec, Jacek A; Lear, Scott A; Pencharz, James; Rhodes, Ryan E; Esdaile, John M

    2013-01-01

    with OA tend to be more motivated to adopt an active lifestyle (ie, at the early stage of OA). Our approach, which consisted of the identification of early knee OA followed immediately by an online intervention that directly targets physical inactivity, can be easily implemented across communities. Conclusions Our online intervention directly targets physical inactivity at a time when the joint damage tends to be mild. If OPEN is found to be effective in changing long-term physical activity behaviors, it opens further opportunities to promote early diagnosis and to implement lifestyle interventions. Trial Registration Clinicaltrial.gov: NCT01608282; http://clinicaltrials.gov/ct2/show/NCT01608282 (Archived by WebCite at http://www.webcitation.org/6G7sBBayI) PMID:23659903

  3. Parietal Epithelial Cell Activation Marker in Early Recurrence of FSGS in the Transplant

    PubMed Central

    Fatima, Huma; Moeller, Marcus J.; Smeets, Bart; Yang, Hai-Chun; D’Agati, Vivette D.; Alpers, Charles E.

    2012-01-01

    Summary Background and objectives Podocyte loss is key in glomerulosclerosis. Activated parietal epithelial cells are proposed to contribute to pathogenesis of glomerulosclerosis and may serve as stem cells that can transition to podocytes. CD44 is a marker for activated parietal epithelial cells. This study investigated whether activated parietal epithelial cells are increased in early recurrent FSGS in transplant compared with minimal change disease. Design, setting, participants, & measurements CD44 staining in renal allograft biopsies from 12 patients with recurrent FSGS was performed and compared with native kidneys with minimal change disease or FSGS and normal control native and transplant kidneys without FSGS. CD44+ epithelial cells along Bowman’s capsule in the parietal epithelial cell location and over the glomerular tuft in the visceral epithelial cell location were assessed. Results Cases with early recurrent FSGS manifesting only foot process effacement showed significantly increased CD44+ visceral epithelial cells involving 29.0% versus 2.6% of glomeruli in minimal change disease and 0% in non-FSGS transplants. Parietal location CD44 positivity also was numerically increased in recurrent FSGS. In later transplant biopsies, glomeruli with segmental lesions had more CD44+ visceral epithelial cells than glomeruli without lesions. Conclusions Parietal epithelial cell activation marker is significantly increased in evolving FSGS versus minimal change disease, and this increase may distinguish early FSGS from minimal change disease. Whether parietal epithelial cell activation contributes to pathogenesis of sclerosis in idiopathic FSGS or is a regenerative/repair response to replace injured podocytes awaits additional study. PMID:22917699

  4. Leptin stimulates hepatic activation of thyroid hormones and promotes early posthatch growth in the chicken.

    PubMed

    Li, Rongjie; Hu, Yan; Ni, Yingdong; Xia, Dong; Grossmann, Roland; Zhao, Ruqian

    2011-10-01

    Hepatic iodothyronine deiodinases (Ds) are involved in the conversion of thyroid hormones (THs) which interacts with growth hormone (GH) to regulate posthatch growth in the chicken. Previous studies suggest that leptin-like immunoreactive substance deposited in the egg may serve as a maternal signal to program posthatch growth. To test the hypothesis that maternal leptin may affect early posthatch growth through modifying hepatic activation of THs, we injected 5.0μg of recombinant murine leptin into the albumen of breeder eggs before incubation. Furthermore, chicken embryo hepatocytes (CEHs) were treated with leptin in vitro to reveal the direct effect of leptin on expression and activity of Ds. In ovo leptin administration markedly accelerated early posthatch growth, elevated serum levels of total and free triiodothyronine (tT3 and fT3), while that of total thyroxin (tT4) remained unchanged. Hepatic mRNA expression and activity of D1 which converts T4 to T3 or rT3 to T2, were significantly increased in leptin-treated chickens, while those of D3 which converts T3 to T2 or T4 to rT3, were significantly decreased. Moreover, hepatic expression of GHR and IGF-I mRNA was all up-regulated in leptin-treated chickens. Males demonstrated more pronounced responses. A direct effect of leptin on Ds was shown in CEHs cultured in vitro. Expression and activity of D1 were increased, whereas those of D3 were decreased, in leptin-treated cells. These data suggest that in ovo leptin administration improves early posthatch growth, in a gender-specific fashion, probably through improving hepatic activation of THs and up-regulating hepatic expression of GHR and IGF-I.

  5. Repurposing psychiatric medicines to target activated microglia in anxious mild cognitive impairment and early Parkinson's disease.

    PubMed

    Lauterbach, Edward C

    2016-01-01

    Anxiety is common in the Mild Cognitive Impairment (MCI) stage of Alzheimer's disease (AD) and the pre-motor stages of Parkinson's disease (PD). A concomitant and possible cause of this anxiety is microglial activation, also considered a key promoter of neurodegeneration in MCI and early PD via inflammatory mechanisms and the generation of degenerative proinflammatory cytokines. Psychiatric disorders, prevalent in AD and PD, are often treated with psychiatric drugs (psychotropics), raising the question of whether psychotropics might therapeutically affect microglial activation, MCI, and PD. The literature of common psychotropics used in treating psychiatric disorders was reviewed for preclinical and clinical findings regarding microglial activation. Findings potentially compatible with reduced microglial activation or reduced microglial inflammogen release were evident for: antipsychotics including neuroleptics (chlorpromazine, thioridazine, loxapine) and atypicals (aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone); mood stabilizers (carbamazepine, valproate, lithium); antidepressants including tricyclics (amitriptyline, clomipramine, imipramine, nortriptyline), SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline), venlafaxine, and bupropion; benzodiazepine anxiolytics (clonazepam, diazepam); cognitive enhancers (donepezil, galantamine, memantine); and other drugs (dextromethorphan, quinidine, amantadine). In contrast, pramipexole and methylphenidate might promote microglial activation. The most promising replicated findings of reduced microglial activation are for quetiapine, valproate, lithium, fluoxetine, donepezil, and memantine but further study is needed and translation of their microglial effects to human disease still requires investigation. In AD-relevant models, risperidone, valproate, lithium, fluoxetine, bupropion, donepezil, and memantine have therapeutic microglial effects in need of replication. Limited

  6. Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease

    PubMed Central

    Roy, Dheeraj S.; Arons, Autumn; Mitchell, Teryn I.; Pignatelli, Michele; Ryan, Tomás J.; Tonegawa, Susumu

    2016-01-01

    Summary Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory decline and subsequent loss of broader cognitive functions1. Memory decline in early stages of Alzheimer’s is mostly limited to episodic memory, for which the hippocampus (HPC) plays a crucial role2. However, it has been uncertain whether the observed amnesia in early stages of Alzheimer’s is due to disrupted encoding and consolidation of episodic information, or an impairment in the retrieval of stored memory information. Here we show that in transgenic mouse models of early Alzheimer’s, direct optogenetic activation of hippocampal memory engram cells results in memory retrieval despite the fact that these mice are amnesic in long-term memory tests when natural recall cues are utilized, revealing a retrieval, rather than a storage impairment. Prior to amyloid plaque deposition, the amnesia in these mice is age-dependent3–5, which correlates with a progressive reduction of spine density of hippocampal dentate gyrus (DG) engram cells. We show that optogenetic induction of long-term potentiation (LTP) at perforant path (PP) synapses of DG engram cells restores both spine density and long-term memory. We also demonstrate that an ablation of DG engram cells containing restored spine density prevents the rescue of long-term memory. Thus, selective rescue of spine density in engram cells may lead to an effective strategy for treating memory loss in early stages of Alzheimer’s disease. PMID:26982728

  7. Memory retrieval by activating engram cells in mouse models of early Alzheimer's disease.

    PubMed

    Roy, Dheeraj S; Arons, Autumn; Mitchell, Teryn I; Pignatelli, Michele; Ryan, Tomás J; Tonegawa, Susumu

    2016-03-24

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory decline and subsequent loss of broader cognitive functions. Memory decline in the early stages of AD is mostly limited to episodic memory, for which the hippocampus has a crucial role. However, it has been uncertain whether the observed amnesia in the early stages of AD is due to disrupted encoding and consolidation of episodic information, or an impairment in the retrieval of stored memory information. Here we show that in transgenic mouse models of early AD, direct optogenetic activation of hippocampal memory engram cells results in memory retrieval despite the fact that these mice are amnesic in long-term memory tests when natural recall cues are used, revealing a retrieval, rather than a storage impairment. Before amyloid plaque deposition, the amnesia in these mice is age-dependent, which correlates with a progressive reduction in spine density of hippocampal dentate gyrus engram cells. We show that optogenetic induction of long-term potentiation at perforant path synapses of dentate gyrus engram cells restores both spine density and long-term memory. We also demonstrate that an ablation of dentate gyrus engram cells containing restored spine density prevents the rescue of long-term memory. Thus, selective rescue of spine density in engram cells may lead to an effective strategy for treating memory loss in the early stages of AD. PMID:26982728

  8. Early Activation of Th2/Th22 Inflammatory and Pruritogenic Pathways in Acute Canine Atopic Dermatitis Skin Lesions.

    PubMed

    Olivry, Thierry; Mayhew, David; Paps, Judy S; Linder, Keith E; Peredo, Carlos; Rajpal, Deepak; Hofland, Hans; Cote-Sierra, Javier

    2016-10-01

    Determining inflammation and itch pathway activation in patients with atopic dermatitis (AD) is fraught with the inability to precisely assess the age of skin lesions, thus affecting the analysis of time-dependent mediators. To characterize inflammatory events occurring during early experimental acute AD lesions, biopsy samples were collected 6, 24, and 48 hours after epicutaneous application of Dermatophagoides farinae house dust mites to sensitized atopic dogs. The skin transcriptome was assessed using a dog-specific microarray and quantitative PCR. Acute canine AD skin lesions had a significant up-regulation of genes encoding T helper (Th) 2 (e.g., IL4, IL5, IL13, IL31, and IL33), Th9 (IL9), and Th22 (IL22) cytokines as well as Th2-promoting chemokines such as CCL5 and CCL17. Proinflammatory (e.g., IL6, LTB, and IL18) cytokines were also up-regulated. Other known pruritogenic pathways were also activated: there was significant up-regulation of genes encoding proteases cathepsin S (CTSS), mast cell chymase (CMA1), tryptase (TPS1) and mastin, neuromedin-B (NMB), nerve growth factor (NGF), and leukotriene-synthesis enzymes (ALOX5, ALOX5AP, and LTA4H). Experimental acute canine house dust mite-induced AD lesions exhibit an activation of innate and adaptive immune responses and pruritogenic pathways similar to those seen in humans with acute AD, thereby validating this model to test innovative therapeutics modalities for this disease.

  9. Views of Adolescent Female Youth on Physical Activity During Early Adolescence

    PubMed Central

    Yungblut, Hope E.; Schinke, Robert J.; McGannon, Kerry R.

    2012-01-01

    Early adolescence is a time when a transition away from sport and physical activity participation is at its highest level among female youth (Hedstrom & Gould, 2004). This has led to the identification of barriers and facilitators of physical activity participation for adolescent females. Consequently there have been calls to overcome barriers and augment facilitators via the creation of gender-relevant programming. Despite these calls and efforts, a gender disparity remains, and a detailed understanding of how girls experience and interpret physical activity within the context of their lives is still lacking. The current project aimed to gain further insight into the foregoing using tenets of Interpretive Phenomenology to further understand the lived physical activity experiences of females during early adolescence, delineating their barriers to participation and the factors enabling participation. Five themes were identified and made into vignettes to facilitate understanding from adolescent females' perspectives: friends or don't know anyone, good or not good enough, fun or not fun; good feeling or gross; and peer support or peer pressure. The physical activity promotion implications for female youth are discussed within the context of these themes. Key points Please provide 3-5 bullet points of the study. Inductive qualitative methodologies can encourage the much-needed voice of female youth in sport and physical activity research. Vignettes serve, not only as a method to illustrate data, but also as a medium to teach contextually relevant information to participants and sport science service providers. The barriers and solutions to female youth engagement in physical activity are best understood through the perspectives of the intended participant. Female youth can serve as central informants in the development and analysis of research projects relating to female youth physical activity. PMID:24149121

  10. Human T cell activation. III. Induction of an early activation antigen, EA 1 by TPA, mitogens and antigens

    SciTech Connect

    Hara, T.; Jung, L.K.L.; FU, S.M.

    1986-03-01

    With human T cells activated for 12 hours by 12-o-tetradecanoyl phorbol-13-acetate (TPA) as immunogen, an IgG/sub 2a/ monoclonal antibody, mAb Ea 1, has been generated to a 60KD phosphorylated protein with 32KD and 28KD subunits. The antigen, Ea 1, is readily detected on 60% of isolated thymocytes by indirect immunofluorescence. A low level of Ea 1 expression is detectable on 2-6% of blood lymphocytes. Isolated T cells have been induced to express Ea 1 by TPA, mitogens and anitgens. TPA activated T cells express Ea 1 as early as 1 hour after activation. By 4 hours, greater than 95% of the T cells stain with mAb Ea 1. About 50% of the PHA or Con A activated T cells express Ea 1 with a similar kinetics. Ea 1 expression proceeds that of IL-2 receptor in these activation processes. T cells activated by soluble antigens (tetanus toxoid and PPD) and alloantigens in MLR also express Ea 1 after a long incubation. About 20% of the T cells stain for Ea 1 at day 6. Ea 1 expression is not limited to activated T cells. B cells activated by TPA or anti-IgM Ab plus B cell growth factor express Ea 1. The kinetics of Ea 1 expression is slower and the staining is less intense. Repeated attempts to detect Ea 1 on resting and activated monocytes and granulocytes have not been successful. Ea 1 expression is due to de novo synthesis for its induction is blocked by cycloheximide and actinomycin D. Ea 1 is the earliest activation antigen detectable to-date.

  11. Event-related potentials reveal early activation of body part representations in action concept comprehension.

    PubMed

    Lu, Aitao; Liu, Jing; Zhang, John X

    2012-03-01

    With tasks involving action concept comprehension, many fMRI studies have reported brain activations in sensori-motor regions specific to effectors of the referent action. There is relatively less evidence whether such activations reflect early semantic access or late conceptual re-processing. Here we recorded event-related potentials when participants recognized noun-verb pairs. For Congruent pairs, the verb was the one most commonly associated with the noun (e.g., football-kick). Compared with a control condition, verbs in Congruent pairs showed priming effects in the time windows of 100-150 ms and 210-260 ms. Such activation seems to be specific to body part but not other aspects of the action as similar priming effect was also found when the noun and verb involved different actions though sharing the same body part (e.g., football-jump), documenting for the first time the early activation of body part representations in action concept comprehension. PMID:22306088

  12. Event-related potentials reveal early activation of body part representations in action concept comprehension.

    PubMed

    Lu, Aitao; Liu, Jing; Zhang, John X

    2012-03-01

    With tasks involving action concept comprehension, many fMRI studies have reported brain activations in sensori-motor regions specific to effectors of the referent action. There is relatively less evidence whether such activations reflect early semantic access or late conceptual re-processing. Here we recorded event-related potentials when participants recognized noun-verb pairs. For Congruent pairs, the verb was the one most commonly associated with the noun (e.g., football-kick). Compared with a control condition, verbs in Congruent pairs showed priming effects in the time windows of 100-150 ms and 210-260 ms. Such activation seems to be specific to body part but not other aspects of the action as similar priming effect was also found when the noun and verb involved different actions though sharing the same body part (e.g., football-jump), documenting for the first time the early activation of body part representations in action concept comprehension.

  13. Early planning activity in frontal and parietal cortex in a simplified task

    PubMed Central

    Andersen, Richard A.

    2015-01-01

    Cortical planning activity has traditionally been probed with visual targets. However, external sensory signals might obscure early correlates of internally generated plans. We devised a nonspatial decision-making task in which the monkey is encouraged to decide randomly whether to reach or saccade in the absence of sensory stimuli. Neurons in frontal and parietal planning areas (in and around the arcuate and intraparietal sulci) showed responses predictive of the monkey's upcoming movement at early stages during the planning process. Neurons predicted the animal's future movements several seconds beforehand, sometimes before the trial even began. These data cast new light on the role of the cerebral cortex in the action planning process, when the animal is free to decide on his own actions in the absence of extraneous sensory cues. PMID:25761951

  14. Monitoring cow activity and rumination time for an early detection of heat stress in dairy cow

    NASA Astrophysics Data System (ADS)

    Abeni, Fabio; Galli, Andrea

    2016-08-01

    The aim of this study was to explore the use of cow activity and rumination time by precision livestock farming tools as early alert for heat stress (HS) detection. A total of 58 Italian Friesian cows were involved in this study during summer 2015. Based on the temperature humidity index (THI), two different conditions were compared on 16 primiparous and 11 multiparous, to be representative of three lactation phases: early (15-84 DIM), around peak (85-154 DIM), and plateau (155-224 DIM). A separate dataset for the assessment of the variance partition included all the cows in the herd from June 7 to July 16. The rumination time (RT2h, min/2 h) and activity index (AI2h, bouts/2 h) were summarized every 2-h interval. The raw data were used to calculate the following variables: total daily RT (RTt), daytime RT (RTd), nighttime RT (RTn), total daily AI (AIt), daytime AI (AId), and nighttime AI (AIn). Either AIt and AId increased, whereas RTt, RTd, and RTn decreased with higher THI in all the three phases. The highest decrease was recorded for RTd and ranged from 49 % (early) to 45 % (plateau). The contribution of the cow within lactation phase was above 60 % of the total variance for AI traits and a share from 33.9 % (for RTt) to 54.8 % (RTn) for RT traits. These observations must be extended to different feeding managements and different animal genetics to assess if different thresholds could be identified to set an early alert system for the farmer.

  15. ERP adaptation provides direct evidence for early mirror neuron activation in the inferior parietal lobule.

    PubMed

    Möhring, Nicole; Brandt, Emily S L; Mohr, Bettina; Pulvermüller, Friedemann; Neuhaus, Andres H

    2014-10-01

    Mirror neuron systems are frequently investigated by assessing overlapping brain activity during observation and execution of actions; however, distinct neuronal subpopulations may be activated that fall below the spatial resolution of magnetic resonance techniques. This shortfall can be resolved using repetition suppression paradigms that identify physiological adaptation processes caused by repeated activation of identical neuronal circuits. Here, event-related potentials were used to investigate the time course of mirror neuron circuit activation using repetition suppression within and across action observation and action execution modalities. In a lip-reading and speech production paradigm, the N170 component indexed stimulus repetition by adapting to both cross-modal and intra-modal repetitions in the left hemisphere. Neuronal source localization revealed activation of the left inferior parietal lobule during cross-modal relative to intra-modal trials. These results provide support for the position that the same neuronal circuits are activated in perceiving and performing articulatory actions. Moreover, our data strongly suggest that inferior parietal lobule mirror neurons are activated relatively early in time, which indicates partly automatic processes of linguistic perception and mirroring. Repetition suppression paradigms therefore help to elucidate neuronal correlates of different cognitive processes and may serve as a starting point for advanced electrophysiological research on mirror neurons.

  16. ERP adaptation provides direct evidence for early mirror neuron activation in the inferior parietal lobule.

    PubMed

    Möhring, Nicole; Brandt, Emily S L; Mohr, Bettina; Pulvermüller, Friedemann; Neuhaus, Andres H

    2014-10-01

    Mirror neuron systems are frequently investigated by assessing overlapping brain activity during observation and execution of actions; however, distinct neuronal subpopulations may be activated that fall below the spatial resolution of magnetic resonance techniques. This shortfall can be resolved using repetition suppression paradigms that identify physiological adaptation processes caused by repeated activation of identical neuronal circuits. Here, event-related potentials were used to investigate the time course of mirror neuron circuit activation using repetition suppression within and across action observation and action execution modalities. In a lip-reading and speech production paradigm, the N170 component indexed stimulus repetition by adapting to both cross-modal and intra-modal repetitions in the left hemisphere. Neuronal source localization revealed activation of the left inferior parietal lobule during cross-modal relative to intra-modal trials. These results provide support for the position that the same neuronal circuits are activated in perceiving and performing articulatory actions. Moreover, our data strongly suggest that inferior parietal lobule mirror neurons are activated relatively early in time, which indicates partly automatic processes of linguistic perception and mirroring. Repetition suppression paradigms therefore help to elucidate neuronal correlates of different cognitive processes and may serve as a starting point for advanced electrophysiological research on mirror neurons. PMID:25017963

  17. Functional activation of the egr-1 (early growth response-1) gene by hydrogen peroxide.

    PubMed

    Nose, K; Ohba, M

    1996-06-01

    The redox-based regulation of gene expression is one of the fundamental mechanisms of cellular functions, and hydrogen peroxide seems to act as an intracellular second messenger of signal transduction of cytokines. Hydrogen peroxide at non-toxic doses induced the accumulation of mRNA for the early growth response-1 (egr-1) gene in mouse osteoblastic cells. The Egr-1 protein is a transcription factor that binds the GCGGGGGCG sequence and contains a zinc-finger structure that is essential for DNA binding. Egr-1 protein is sensitive to oxidative stress and loses specific DNA-binding activity when exposed to high levels of oxidative stress. Incubating cells with hydrogen peroxide at about 50 microM, however, increased the accumulation of Egr-1 protein, and the Egr-1 product seemed to be functional, judging by its binding activity to the GCGGGGGCG sequence and its ability to activate the chloramphenicol acetyltransferase reporter gene under the control of the human thymidine kinase enhancer containing the Egr-1 binding sequence. It was reported that the activity of Egr-1 protein as a transcription factor was negatively regulated by active oxygens. However, with appropriate concentrations of active oxygen, its capacity to bind a specific DNA sequence and to enhance the transcriptional activity of target genes is thought to be elevated.

  18. Urinary Aminopeptidase Activities as Early and Predictive Biomarkers of Renal Dysfunction in Cisplatin-Treated Rats

    PubMed Central

    Quesada, Andrés; Vargas, Félix; Montoro-Molina, Sebastián; O'Valle, Francisco; Rodríguez-Martínez, María Dolores; Osuna, Antonio; Prieto, Isabel; Ramírez, Manuel; Wangensteen, Rosemary

    2012-01-01

    This study analyzes the fluorimetric determination of alanyl- (Ala), glutamyl- (Glu), leucyl-cystinyl- (Cys) and aspartyl-aminopeptidase (AspAp) urinary enzymatic activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats. Male Wistar rats (n = 8 each group) received a single subcutaneous injection of either saline or cisplatin 3.5 or 7 mg/kg, and urine samples were taken at 0, 1, 2, 3 and 14 days after treatment. In urine samples we determined Ala, Glu, Cys and AspAp activities, proteinuria, N-acetyl-β-D-glucosaminidase (NAG), albumin, and neutrophil gelatinase-associated lipocalin (NGAL). Plasma creatinine, creatinine clearance and renal morphological variables were measured at the end of the experiment. CysAp, NAG and albumin were increased 48 hours after treatment in the cisplatin 3.5 mg/kg treated group. At 24 hours, all urinary aminopeptidase activities and albuminuria were significantly increased in the cisplatin 7 mg/kg treated group. Aminopeptidase urinary activities correlated (p<0.011; r2>0.259) with plasma creatinine, creatinine clearance and/or kidney weight/body weight ratio at the end of the experiment and they could be considered as predictive biomarkers of renal injury severity. ROC-AUC analysis was made to study their sensitivity and specificity to distinguish between treated and untreated rats at day 1. All aminopeptidase activities showed an AUC>0.633. We conclude that Ala, Cys, Glu and AspAp enzymatic activities are early and predictive urinary biomarkers of the renal dysfunction induced by cisplatin. These determinations can be very useful in the prognostic and diagnostic of renal dysfunction in preclinical research and clinical practice. PMID:22792302

  19. Early LPS-induced ERK activation in retinal pigment epithelium cells is dependent on PIP 2 -PLC.

    PubMed

    Mateos, Melina V; Kamerbeek, Constanza B; Giusto, Norma M; Salvador, Gabriela A

    2016-06-01

    This article presents additional data regarding the study "The phospholipase D pathway mediates the inflammatory response of the retinal pigment epithelium" [1]. The new data presented here show that short exposure of RPE cells to lipopolysaccharide (LPS) induces an early and transient activation of the extracellular signal-regulated kinase (ERK1/2). This early ERK1/2 activation is dependent on phosphatidylinositol bisphosphate-phospholipase C (PIP2-PLC). On the contrary, neither the phospholipase D 1 (PLD1) nor the PLD2 inhibition is able to modulate the early ERK1/2 activation induced by LPS in RPE cells.

  20. Early Proterozoic activity on Archean faults in the western Superior province - evidence from pseudotachylite

    USGS Publications Warehouse

    Peterman, Z.E.; Day, W.

    1989-01-01

    Major transcurrent faults in the Superior province developed in the Late Archean at the close of the Kenoran orogeny. Reactivation of some of these faults late in the Early Proterozoic is indicated by Rb-Sr analyses of pseudotachylite from the Rainy Lake-Seine River and Quetico faults in the Rainy Lake region of Minnesota and Ontario. Fault veins of pseudotachylite and immediately adjacent country rock at two localities yielded subparallel isochrons that are pooled for an age of 1947??23 Ma. K-Ar and Rb-Sr biotite ages register earlier regional cooling of the terrane at about 2500 Ma with no evidence of younger thermal overprinting at temperatures exceeding 300??C. Accordingly, the 1947??23 Ma age is interpreted as dating the formation of the pseudotachylite. Reactivation of existing faults at this time was caused by stresses transmitted from margins of the Superior province where compressional tectonic events were occurring. -Authors

  1. Changing Balance of Spinal Cord Excitability and Nociceptive Brain Activity in Early Human Development.

    PubMed

    Hartley, Caroline; Moultrie, Fiona; Gursul, Deniz; Hoskin, Amy; Adams, Eleri; Rogers, Richard; Slater, Rebeccah

    2016-08-01

    In adults, nociceptive reflexes and behavioral responses are modulated by a network of brain regions via descending projections to the spinal dorsal horn [1]. Coordinated responses to noxious inputs manifest from a balance of descending facilitation and inhibition. In contrast, young infants display exaggerated and uncoordinated limb reflexes [2]. Our understanding of nociceptive processing in the infant brain has been advanced by the use of electrophysiological and hemodynamic imaging [3-6]. From approximately 35 weeks' gestation, nociceptive-specific patterns of brain activity emerge [7], whereas prior to this, non-specific bursts of activity occur in response to noxious, tactile, visual, and auditory stimulation [7-10]. During the preterm period, refinement of spinal cord excitability is also observed: reflex duration shortens, response threshold increases, and improved discrimination between tactile and noxious events occurs [2, 11, 12]. However, the development of descending modulation in human infants remains relatively unexplored. In 40 infants aged 28-42 weeks' gestation, we examined the relationship between nociceptive brain activity and spinal reflex withdrawal activity in response to a clinically essential noxious procedure. Nociceptive-specific brain activity increases in magnitude with gestational age, whereas reflex withdrawal activity decreases in magnitude, duration, and latency across the same developmental period. By recording brain and spinal cord activity in the same infants, we demonstrate that the maturation of nociceptive brain activity is concomitant with the refinement of noxious-evoked limb reflexes. We postulate that, consistent with studies in animals, infant reflexes are influenced by the development of top-down inhibitory modulation from maturing subcortical and cortical brain networks. PMID:27374336

  2. The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex.

    PubMed

    Self, Matthew W; Peters, Judith C; Possel, Jessy K; Reithler, Joel; Goebel, Rainer; Ris, Peterjan; Jeurissen, Danique; Reddy, Leila; Claus, Steven; Baayen, Johannes C; Roelfsema, Pieter R

    2016-03-01

    Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive fields with tunings for contrast, orientation, spatial frequency, and size, similar to those reported in the macaque. We also observed pronounced gamma oscillations in the local-field potential that could be used to estimate the underlying spiking response properties. Spiking responses were modulated by visual context and attention. We observed orientation-tuned surround suppression: responses were suppressed by image regions with a uniform orientation and enhanced by orientation contrast. Additionally, responses were enhanced on regions that perceptually segregated from the background, indicating that neurons in the human visual cortex are sensitive to figure-ground structure. Spiking responses were also modulated by object-based attention. When the patient mentally traced a curve through the neurons' receptive fields, the accompanying shift of attention enhanced neuronal activity. These results demonstrate that the tuning properties of cells in the human early visual cortex are similar to those in the macaque and that responses can be modulated by both contextual factors and behavioral relevance. Our results, therefore, imply that the macaque visual system is an excellent model for the human visual cortex. PMID:27015604

  3. The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex

    PubMed Central

    Reithler, Joel; Goebel, Rainer; Ris, Peterjan; Jeurissen, Danique; Reddy, Leila; Claus, Steven; Baayen, Johannes C.; Roelfsema, Pieter R.

    2016-01-01

    Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive fields with tunings for contrast, orientation, spatial frequency, and size, similar to those reported in the macaque. We also observed pronounced gamma oscillations in the local-field potential that could be used to estimate the underlying spiking response properties. Spiking responses were modulated by visual context and attention. We observed orientation-tuned surround suppression: responses were suppressed by image regions with a uniform orientation and enhanced by orientation contrast. Additionally, responses were enhanced on regions that perceptually segregated from the background, indicating that neurons in the human visual cortex are sensitive to figure-ground structure. Spiking responses were also modulated by object-based attention. When the patient mentally traced a curve through the neurons’ receptive fields, the accompanying shift of attention enhanced neuronal activity. These results demonstrate that the tuning properties of cells in the human early visual cortex are similar to those in the macaque and that responses can be modulated by both contextual factors and behavioral relevance. Our results, therefore, imply that the macaque visual system is an excellent model for the human visual cortex. PMID:27015604

  4. Early base-pair fluctuations and the activation of mRNA splicing

    NASA Astrophysics Data System (ADS)

    Fernández, Ariel

    1991-05-01

    By means of multiprocessed Monte Carlo simulations we study the amplification in time structural fluctuations in sequential RNA folding concomitant with transcription. The simulations allow for an exploration of configuration space subject to the realistic time-constraints of RNA synthesis. The treatment focuses on the splicing YC4 intron as a study case. We show how an early disruption in the folding may result in a terminal structure which is active for splicing, bringing together the two cleavage sites at both ends of the intron.

  5. When Two Isn't Better than One: Predictors of Early Sexual Activity in Adolescence Using a Cumulative Risk Model

    ERIC Educational Resources Information Center

    Price, Myeshia N.; Hyde, Janet Shibley

    2009-01-01

    This study explored factors that may be associated with early initiation of sexual activity among adolescents. Using the cumulative risk model, we hypothesized that as exposure to risk factors increases, so does the likelihood of early sexual debut. A sample of 273 (53% girls, 90% European American) adolescents was followed longitudinally from age…

  6. Group-Based Modeling of Time Spent in Structured Activity Trajectories from Middle Childhood into Early Adolescence

    ERIC Educational Resources Information Center

    Mata, Andrea D.; van Dulmen, Manfred H. M.

    2012-01-01

    This study investigated trajectories of time spent in structured activities from middle childhood to early adolescence by using data from the National Institute of Child Health & Human Development (NICHD) Study of Early Child Care. We used latent class growth analyses and identified five trajectories (stable low, increasing high, decreasing low,…

  7. NK cells, displaying early activation, cytotoxicity and adhesion molecules, are associated with mild dengue disease

    PubMed Central

    Azeredo, E L; De Oliveira-Pinto, L M; Zagne, S M; Cerqueira, D I S; Nogueira, R M R; Kubelka, C F

    2006-01-01

    During the innate immune response against infections, Natural Killer (NK) cells are as important effector cells as are Cytotoxic T lymphocytes (CTL) generated after antigenic stimulation in the adaptative response. NK cells increase in numbers, after viral infection or vaccination. We investigated the NK cell and CD8 T lymphocyte status in 55 dengue infected patients. The NK (CD56+CD3−) and CD56+ T cell (CD56+CD3+) rates rise during the acute phase of disease. The majority of NK cells from dengue patients display early markers for activation (CD69, HLA-DR, and CD38) and cell adhesion molecules (CD44, CD11a) during the acute phase of disease. The intracellular cytotoxic granule, TIA-1, is also up-regulated early in NK cells. Most of these markers appear also on CD8+ T lymphocytes but during the late acute phase. Circulating IL-15 is elevated in a significant number of patients during early acute infection and its values were statistically correlated with NK frequencies and cytotoxic markers on NKs. We have therefore shown that dengue virus infection is very likely stimulating a cytotoxic response that may be efficient in controlling the virus in synergism with CD8+ T lymphocytes. Interestingly, the heightened CD56+CD3−, CD56+CD3+, CD56+TIA-1+ and CD56+CD11a+ cell rates are associated with mild dengue clinical manifestations and might indicate a good prognosis of the disease. PMID:16412060

  8. Renin-Angiotensin Activation and Oxidative Stress in Early Heart Failure with Preserved Ejection Fraction.

    PubMed

    Negi, Smita I; Jeong, Euy-Myoung; Shukrullah, Irfan; Veleder, Emir; Jones, Dean P; Fan, Tai-Hwang M; Varadarajan, Sudhahar; Danilov, Sergei M; Fukai, Tohru; Dudley, Samuel C

    2015-01-01

    Animal models have suggested a role of renin-angiotensin system (RAS) activation and subsequent cardiac oxidation in heart failure with preserved ejection fraction (HFpEF). Nevertheless, RAS blockade has failed to show efficacy in treatment of HFpEF. We evaluated the role of RAS activation and subsequent systemic oxidation in HFpEF. Oxidative stress markers were compared in 50 subjects with and without early HFpEF. Derivatives of reactive oxidative metabolites (DROMs), F2-isoprostanes (IsoPs), and ratios of oxidized to reduced glutathione (E h GSH) and cysteine (E h CyS) were measured. Angiotensin converting enzyme (ACE) levels and activity were measured. On univariate analysis, HFpEF was associated with male sex (p = 0.04), higher body mass index (BMI) (p = 0.003), less oxidized E h CyS (p = 0.001), lower DROMs (p = 0.02), and lower IsoP (p = 0.03). Higher BMI (OR: 1.3; 95% CI: 1.1-1.6) and less oxidized E h CyS (OR: 1.2; 95% CI: 1.1-1.4) maintained associations with HFpEF on multivariate analysis. Though ACE levels were higher in early HFpEF (OR: 1.09; 95% CI: 1.01-1.05), ACE activity was similar to that in controls. HFpEF is not associated with significant systemic RAS activation or oxidative stress. This may explain the failure of RAS inhibitors to alter outcomes in HFpEF. PMID:26504834

  9. Semen activates the female immune response during early pregnancy in mice.

    PubMed

    Johansson, Martina; Bromfield, John J; Jasper, Melinda J; Robertson, Sarah A

    2004-06-01

    Insemination elicits inflammatory changes in female reproductive tissues, but whether this results in immunological priming to paternal antigens or influences pregnancy outcome is not clear. We have evaluated indices of lymphocyte activation in lymph nodes draining the uterus following allogeneic mating in mice and have investigated the significance of sperm and plasma constituents of semen in the response. At 4 days after mating, there was a 1b7-fold increase in the cellularity of the para-aortic lymph node (PALN) compared with virgin controls. PALN lymphocytes were principally T and B lymphocytes, with smaller populations of CD3(+) B220(lo), NK1.1(+) CD3(-) (NK) and NK1.1(+) CD3(+) (NKT) cells. CD69 expression indicative of activation was increased after mating and was most evident in CD3(+) and NK1.1(+) cells. Synthesis of cytokines including interleukin-2, interleukin-4 and interferon-gamma was elevated in CD3(+) PALN cells after exposure to semen, as assessed by intracellular cytokine fluorescence-activated cell sorting, immunohistochemistry and quantitative reverse transcriptase polymerase chain reaction. Matings with vasectomized males indicated that the lymphocyte activation occurs independently of sperm. However, in contrast, males from which seminal vesicle glands were surgically removed failed to stimulate PALN cell proliferation or cytokine synthesis. Adoptive transfer experiments using radiolabelled lymphocytes from mated mice showed that lymphocytes activated at insemination home to embryo implantation sites in the uterus as well as other mucosal tissues and lymph nodes. These findings indicate that activation and expansion of female lymphocyte populations occurs after mating, and is triggered by constituents of seminal plasma derived from the seminal vesicle glands. Moreover, lymphocytes activated at insemination may help mediate maternal tolerance of the conceptus in the implantation site.

  10. Recent activities of the Seismology Division Early Career Representative(s)

    NASA Astrophysics Data System (ADS)

    Agius, Matthew; Van Noten, Koen; Ermert, Laura; Mai, P. Martin; Krawczyk, CharLotte

    2016-04-01

    The European Geosciences Union is a bottom-up-organisation, in which its members are represented by their respective scientific divisions, committees and council. In recent years, EGU has embarked on a mission to reach out for its numerous 'younger' members by giving awards to outstanding young scientists and the setting up of Early Career Scientists (ECS) representatives. The division representative's role is to engage in discussions that concern students and early career scientists. Several meetings between all the division representatives are held throughout the year to discuss ideas and Union-wide issues. One important impact ECS representatives have had on EGU is the increased number of short courses and workshops run by ECS during the annual General Assembly. Another important contribution of ECS representatives was redefining 'Young Scientist' to 'Early Career Scientist', which avoids discrimination due to age. Since 2014, the Seismology Division has its own ECS representative. In an effort to more effectively reach out for young seismologists, a blog and a social media page dedicated to seismology have been set up online. With this dedicated blog, we'd like to give more depth to the average browsing experience by enabling young researchers to explore various seismology topics in one place while making the field more exciting and accessible to the broader community. These pages are used to promote the latest research especially of young seismologists and to share interesting seismo-news. Over the months the pages proved to be popular, with hundreds of views every week and an increased number of followers. An online survey was conducted to learn more about the activities and needs of early career seismologists. We present the results from this survey, and the work that has been carried out over the last two years, including detail of what has been achieved so far, and what we would like the ECS representation for Seismology to achieve. Young seismologists are

  11. Upregulation of early growth response factor-1 by bile acids requires mitogen-activated protein kinase signaling

    SciTech Connect

    Allen, Katryn; Kim, Nam Deuk; Moon, Jeon-OK; Copple, Bryan L.

    2010-02-15

    Cholestasis results when excretion of bile acids from the liver is interrupted. Liver injury occurs during cholestasis, and recent studies showed that inflammation is required for injury. Our previous studies demonstrated that early growth response factor-1 (Egr-1) is required for development of inflammation in liver during cholestasis, and that bile acids upregulate Egr-1 in hepatocytes. What remains unclear is the mechanism by which bile acids upregulate Egr-1. Bile acids modulate gene expression in hepatocytes by activating the farnesoid X receptor (FXR) and through activation of mitogen-activated protein kinase (MAPK) signaling. Accordingly, the hypothesis was tested that bile acids upregulate Egr-1 in hepatocytes by FXR and/or MAPK-dependent mechanisms. Deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA) stimulated upregulation of Egr-1 to the same extent in hepatocytes isolated from wild-type mice and FXR knockout mice. Similarly, upregulation of Egr-1 in the livers of bile duct-ligated (BDL) wild-type and FXR knockout mice was not different. Upregulation of Egr-1 in hepatocytes by DCA and CDCA was prevented by the MEK inhibitors U0126 and SL-327. Furthermore, pretreatment of mice with U0126 prevented upregulation of Egr-1 in the liver after BDL. Results from these studies demonstrate that activation of MAPK signaling is required for upregulation of Egr-1 by bile acids in hepatocytes and for upregulation of Egr-1 in the liver during cholestasis. These studies suggest that inhibition of MAPK signaling may be a novel therapy to prevent upregulation of Egr-1 in liver during cholestasis.

  12. 18 CFR 707.6 - Early involvement in private, State, local, and other non-Federal activities requiring Federal...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... private, State, local, and other non-Federal activities requiring Federal action. 707.6 Section 707.6..., State, local, and other non-Federal activities requiring Federal action. (a) Section 1501.2(d) of the... approval or action to which NEPA applies. Such activities for which early involvement is...

  13. 18 CFR 707.6 - Early involvement in private, State, local, and other non-Federal activities requiring Federal...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... private, State, local, and other non-Federal activities requiring Federal action. 707.6 Section 707.6..., State, local, and other non-Federal activities requiring Federal action. (a) Section 1501.2(d) of the... approval or action to which NEPA applies. Such activities for which early involvement is...

  14. 18 CFR 707.6 - Early involvement in private, State, local, and other non-Federal activities requiring Federal...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... private, State, local, and other non-Federal activities requiring Federal action. 707.6 Section 707.6..., State, local, and other non-Federal activities requiring Federal action. (a) Section 1501.2(d) of the... approval or action to which NEPA applies. Such activities for which early involvement is...

  15. Early Prediction of Movie Box Office Success Based on Wikipedia Activity Big Data

    PubMed Central

    Mestyán, Márton; Yasseri, Taha; Kertész, János

    2013-01-01

    Use of socially generated “big data” to access information about collective states of the minds in human societies has become a new paradigm in the emerging field of computational social science. A natural application of this would be the prediction of the society's reaction to a new product in the sense of popularity and adoption rate. However, bridging the gap between “real time monitoring” and “early predicting” remains a big challenge. Here we report on an endeavor to build a minimalistic predictive model for the financial success of movies based on collective activity data of online users. We show that the popularity of a movie can be predicted much before its release by measuring and analyzing the activity level of editors and viewers of the corresponding entry to the movie in Wikipedia, the well-known online encyclopedia. PMID:23990938

  16. Early prediction of movie box office success based on Wikipedia activity big data.

    PubMed

    Mestyán, Márton; Yasseri, Taha; Kertész, János

    2013-01-01

    Use of socially generated "big data" to access information about collective states of the minds in human societies has become a new paradigm in the emerging field of computational social science. A natural application of this would be the prediction of the society's reaction to a new product in the sense of popularity and adoption rate. However, bridging the gap between "real time monitoring" and "early predicting" remains a big challenge. Here we report on an endeavor to build a minimalistic predictive model for the financial success of movies based on collective activity data of online users. We show that the popularity of a movie can be predicted much before its release by measuring and analyzing the activity level of editors and viewers of the corresponding entry to the movie in Wikipedia, the well-known online encyclopedia.

  17. Early prediction of movie box office success based on Wikipedia activity big data.

    PubMed

    Mestyán, Márton; Yasseri, Taha; Kertész, János

    2013-01-01

    Use of socially generated "big data" to access information about collective states of the minds in human societies has become a new paradigm in the emerging field of computational social science. A natural application of this would be the prediction of the society's reaction to a new product in the sense of popularity and adoption rate. However, bridging the gap between "real time monitoring" and "early predicting" remains a big challenge. Here we report on an endeavor to build a minimalistic predictive model for the financial success of movies based on collective activity data of online users. We show that the popularity of a movie can be predicted much before its release by measuring and analyzing the activity level of editors and viewers of the corresponding entry to the movie in Wikipedia, the well-known online encyclopedia. PMID:23990938

  18. Ovarian insufficiency and early pregnancy loss induced by activation of the innate immune system

    PubMed Central

    Erlebacher, Adrian; Zhang, Dorothy; Parlow, Albert F.; Glimcher, Laurie H.

    2004-01-01

    We describe a murine model of early pregnancy failure induced by systemic activation of the CD40 immune costimulatory pathway. Although fetal loss involved an NK cell intermediate, it was not due to lymphocyte-mediated destruction of the fetus and placenta. Rather, pregnancy failure resulted from impaired progesterone synthesis by the corpus luteum of the ovary, an endocrine defect in turn associated with ovarian resistance to the gonadotropic effects of prolactin. Pregnancy failure also required the proinflammatory cytokine TNF-α and correlated with the luteal induction of the prolactin receptor signaling inhibitors suppressor of cytokine signaling 1 (Socs1) and Socs3. Such links between immune activation and reproductive endocrine dysfunction may be relevant to pregnancy loss and other clinical disorders of reproduction. PMID:15232610

  19. Bidirectional radial Ca2+ activity regulates neurogenesis and migration during early cortical column formation

    PubMed Central

    Rash, Brian G.; Ackman, James B.; Rakic, Pasko

    2016-01-01

    Cortical columns are basic cellular and functional units of the cerebral cortex that are malformed in many brain disorders, but how they initially develop is not well understood. Using an optogenetic sensor in the mouse embryonic forebrain, we demonstrate that Ca2+ fluxes propagate bidirectionally within the elongated fibers of radial glial cells (RGCs), providing a novel communication mechanism linking the proliferative and postmitotic zones before the onset of synaptogenesis. Our results indicate that Ca2+ activity along RGC fibers provides feedback information along the radial migratory pathway, influencing neurogenesis and migration during early column development. Furthermore, we find that this columnar Ca2+ propagation is induced by Notch and fibroblast growth factor activities classically implicated in cortical expansion and patterning. Thus, cortical morphogens and growth factors may influence cortical column assembly in part by regulating long-distance Ca2+ communication along the radial axis of cortical development. PMID:26933693

  20. Stress fractures of the second metatarsal base occur in nondancers.

    PubMed

    Chuckpaiwong, Bavornrit; Cook, Chad; Nunley, James A

    2007-08-01

    Stress fractures of the base of the second metatarsal are common in ballet dancers and essentially are unreported in nondancers. We presumed base of the second metatarsal stress fractures in nondancers occur in a wide variety of individuals regardless of demographics, are highly associated with athletic activities, and have specific examination findings and poor clinical outcomes. Using a retrospective chart review, we identified 12 stress fractures at the base of the second metatarsal (nine patients) in nondancers. Our review suggests second metatarsal base stress fractures occur in nondancers in a diverse population, and nonoperative treatment provides limited success. Advanced radiographic study, specifically MRI, is useful to assist the early diagnosis and prognostication. All of the stress fractures were treated nonoperatively; six fractures (50%) developed nonunion and five underwent subsequent surgery. The surgery for nonunion provided successful outcomes; however, risk factors such as low bone mass and comorbidities may have played important roles in the prognosis.

  1. Early surgery for hospital-acquired and community-acquired active infective endocarditis.

    PubMed

    Shibata, Toshihiko; Sasaki, Yasuyuki; Hirai, Hidekazu; Fukui, Toshihiro; Hosono, Mitsuharu; Suehiro, Shigefumi

    2007-06-01

    Active infective endocarditis (IE) is classified into two groups; hospital acquired IE (HIE) and IE other than HIE, which was defined as community-acquired IE (CIE). Eighty-two patients underwent surgical treatment for active IE. Seventy-one cases were CIE group and eleven were HIE. There were six patients with native valve endocarditis and five cases of prosthetic valve endocarditis in the HIE group. We compared the surgical outcome of both types of active IE retrospectively. The preoperative status of the patients in the HIE group was more critical than that in the CIE group. Streptococcus spp. were the major micro-organisms in the CIE group (39%), while 82% of the HIE cases were caused by Staphylococcus spp. All Staphylococcus organisms in the HIE group were methicillin resistant. There were 10 hospital deaths, three in the CIE group and seven in the HIE group. Operative mortality in the HIE group was significantly higher than in the CIE group (63.6% vs. 4.2%, P<0.001). The outcome of early operation was satisfactory for active CIE, but poor for HIE. These types of active IE should be considered separately.

  2. Right Occipital Cortex Activation Correlates with Superior Odor Processing Performance in the Early Blind

    PubMed Central

    Grandin, Cécile B.; Dricot, Laurence; Plaza, Paula; Lerens, Elodie; Rombaux, Philippe; De Volder, Anne G.

    2013-01-01

    Using functional magnetic resonance imaging (fMRI) in ten early blind humans, we found robust occipital activation during two odor-processing tasks (discrimination or categorization of fruit and flower odors), as well as during control auditory-verbal conditions (discrimination or categorization of fruit and flower names). We also found evidence for reorganization and specialization of the ventral part of the occipital cortex, with dissociation according to stimulus modality: the right fusiform gyrus was most activated during olfactory conditions while part of the left ventral lateral occipital complex showed a preference for auditory-verbal processing. Only little occipital activation was found in sighted subjects, but the same right-olfactory/left-auditory-verbal hemispheric lateralization was found overall in their brain. This difference between the groups was mirrored by superior performance of the blind in various odor-processing tasks. Moreover, the level of right fusiform gyrus activation during the olfactory conditions was highly correlated with individual scores in a variety of odor recognition tests, indicating that the additional occipital activation may play a functional role in odor processing. PMID:23967263

  3. Early maladaptive schemas activated in patients with obsessive compulsive disorder: A cross-sectional study.

    PubMed

    Atalay, Hakan; Atalay, Figen; Karahan, Dilara; Caliskan, Mecit

    2008-01-01

    Aim. The aim of the present article is to investigate the activation patterns of early maladaptive schemas (EMSs) in patients with obsessive-compulsive disorder (OCD). Method. During the time between 1 January 2006 and 1 April 2006, 45 consecutive patients from an outpatient facility of a general hospital and 45 age- and gender-matched healthy control subjects from the hospital staff were included in the study. They were administered the Structured Clinical Interview for Diagnosis of DSM-IV Mental Disorders (SCID-1), the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-2), the Young Schema Questionnaire-Short Form (YSQ-SF), the Young Parenting Inventory (YPI) and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The results were assessed using GraphPad Prisma V.3 statistical program. Results. The YSQ total score of the OCD group was significantly higher than the control group (t=3.62, P<0.0001). The average scores of the patients with OCD on certain schemas were significantly higher than the average scores of the control group, although the others did not make any difference between the OCD and control groups. Conclusion. The study demonstrates that, in the patients with OCD, most of the early maladaptive schemas including social isolation, vulnerability and pessimism, are prominently activated. PMID:24937713

  4. Solanum lycopersicum AUXIN RESPONSE FACTOR 9 regulates cell division activity during early tomato fruit development

    PubMed Central

    de Jong, Maaike; Wolters-Arts, Mieke; Schimmel, Bernardus C. J.; Stultiens, Catharina L. M.; de Groot, Peter F. M.; Powers, Stephen J.; Tikunov, Yury M.; Bovy, Arnoud G.; Mariani, Celestina; Vriezen, Wim H.; Rieu, Ivo

    2015-01-01

    The transformation of the ovary into a fruit after successful completion of pollination and fertilization has been associated with many changes at transcriptomic level. These changes are part of a dynamic and complex regulatory network that is controlled by phytohormones, with a major role for auxin. One of the auxin-related genes differentially expressed upon fruit set and early fruit development in tomato is Solanum lycopersicum AUXIN RESPONSE FACTOR 9 (SlARF9). Here, the functional analysis of this ARF is described. SlARF9 expression was found to be auxin-responsive and SlARF9 mRNA levels were high in the ovules, placenta, and pericarp of pollinated ovaries, but also in other plant tissues with high cell division activity, such as the axillary meristems and root meristems. Transgenic plants with increased SlARF9 mRNA levels formed fruits that were smaller than wild-type fruits because of reduced cell division activity, whereas transgenic lines in which SlARF9 mRNA levels were reduced showed the opposite phenotype. The expression analysis, together with the phenotype of the transgenic lines, suggests that, in tomato, ARF9 negatively controls cell division during early fruit development. PMID:25883382

  5. Early maladaptive schemas activated in patients with obsessive compulsive disorder: A cross-sectional study.

    PubMed

    Atalay, Hakan; Atalay, Figen; Karahan, Dilara; Caliskan, Mecit

    2008-01-01

    Aim. The aim of the present article is to investigate the activation patterns of early maladaptive schemas (EMSs) in patients with obsessive-compulsive disorder (OCD). Method. During the time between 1 January 2006 and 1 April 2006, 45 consecutive patients from an outpatient facility of a general hospital and 45 age- and gender-matched healthy control subjects from the hospital staff were included in the study. They were administered the Structured Clinical Interview for Diagnosis of DSM-IV Mental Disorders (SCID-1), the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-2), the Young Schema Questionnaire-Short Form (YSQ-SF), the Young Parenting Inventory (YPI) and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The results were assessed using GraphPad Prisma V.3 statistical program. Results. The YSQ total score of the OCD group was significantly higher than the control group (t=3.62, P<0.0001). The average scores of the patients with OCD on certain schemas were significantly higher than the average scores of the control group, although the others did not make any difference between the OCD and control groups. Conclusion. The study demonstrates that, in the patients with OCD, most of the early maladaptive schemas including social isolation, vulnerability and pessimism, are prominently activated.

  6. Solanum lycopersicum AUXIN RESPONSE FACTOR 9 regulates cell division activity during early tomato fruit development.

    PubMed

    de Jong, Maaike; Wolters-Arts, Mieke; Schimmel, Bernardus C J; Stultiens, Catharina L M; de Groot, Peter F M; Powers, Stephen J; Tikunov, Yury M; Bovy, Arnoud G; Mariani, Celestina; Vriezen, Wim H; Rieu, Ivo

    2015-06-01

    The transformation of the ovary into a fruit after successful completion of pollination and fertilization has been associated with many changes at transcriptomic level. These changes are part of a dynamic and complex regulatory network that is controlled by phytohormones, with a major role for auxin. One of the auxin-related genes differentially expressed upon fruit set and early fruit development in tomato is Solanum lycopersicum AUXIN RESPONSE FACTOR 9 (SlARF9). Here, the functional analysis of this ARF is described. SlARF9 expression was found to be auxin-responsive and SlARF9 mRNA levels were high in the ovules, placenta, and pericarp of pollinated ovaries, but also in other plant tissues with high cell division activity, such as the axillary meristems and root meristems. Transgenic plants with increased SlARF9 mRNA levels formed fruits that were smaller than wild-type fruits because of reduced cell division activity, whereas transgenic lines in which SlARF9 mRNA levels were reduced showed the opposite phenotype. The expression analysis, together with the phenotype of the transgenic lines, suggests that, in tomato, ARF9 negatively controls cell division during early fruit development.

  7. Friendship Network Characteristics Are Associated with Physical Activity and Sedentary Behavior in Early Adolescence

    PubMed Central

    Marks, Jennifer; de la Haye, Kayla; Barnett, Lisa M; Allender, Steven

    2015-01-01

    Introduction There is limited understanding of the association between peer social networks and physical activity (PA), sedentary and screen-related behaviors. This study reports on associations between personal network characteristics and these important health behaviors for early adolescents. Methods Participants were 310 students, aged 11–13 years, from fifteen randomly selected Victorian primary schools (43% response rate). PA and sedentary behaviors were collected via accelerometer and self-report questionnaire, and anthropometric measures via trained researchers. Participants nominated up to fifteen friends, and described the frequency of interaction and perceived activity intensity of these friends. Personal network predictors were examined using regression modelling for PA and sedentary/screen behavior. Results Perceived activity levels of friends, and friendships with very frequent interaction were associated with outside-of-school PA and/or sedentary/screen time. Differences according to sex were also observed in the association between network characteristics and PA and sedentary time. A higher number of friends and greater proportion of same sex friends were associated with boys engaging in more moderate-to-vigorous PA outside of school hours. PA intensity during school-day breaks was positively associated with having a greater proportion of friends who played sports for girls, and a greater proportion of male friends for boys. Conclusion Friendship network characteristics are associated with PA and sedentary/screen time in late childhood/early adolescence, and these associations differ by sex. The positive influence of very active peers may be a promising avenue to strengthen traditional interventions for the promotion of PA and reduction in screen time. PMID:26709924

  8. The interplay of early-life stress, nutrition, and immune activation programs adult hippocampal structure and function

    PubMed Central

    Hoeijmakers, Lianne; Lucassen, Paul J.; Korosi, Aniko

    2015-01-01

    Early-life adversity increases the vulnerability to develop psychopathologies and cognitive decline later in life. This association is supported by clinical and preclinical studies. Remarkably, experiences of stress during this sensitive period, in the form of abuse or neglect but also early malnutrition or an early immune challenge elicit very similar long-term effects on brain structure and function. During early-life, both exogenous factors like nutrition and maternal care, as well as endogenous modulators, including stress hormones and mediator of immunological activity affect brain development. The interplay of these key elements and their underlying molecular mechanisms are not fully understood. We discuss here the hypothesis that exposure to early-life adversity (specifically stress, under/malnutrition and infection) leads to life-long alterations in hippocampal-related cognitive functions, at least partly via changes in hippocampal neurogenesis. We further discuss how these different key elements of the early-life environment interact and affect one another and suggest that it is a synergistic action of these elements that shapes cognition throughout life. Finally, we consider different intervention studies aiming to prevent these early-life adversity induced consequences. The emerging evidence for the intriguing interplay of stress, nutrition, and immune activity in the early-life programming calls for a more in depth understanding of the interaction of these elements and the underlying mechanisms. This knowledge will help to develop intervention strategies that will converge on a more complete set of changes induced by early-life adversity. PMID:25620909

  9. The interplay of early-life stress, nutrition, and immune activation programs adult hippocampal structure and function.

    PubMed

    Hoeijmakers, Lianne; Lucassen, Paul J; Korosi, Aniko

    2014-01-01

    Early-life adversity increases the vulnerability to develop psychopathologies and cognitive decline later in life. This association is supported by clinical and preclinical studies. Remarkably, experiences of stress during this sensitive period, in the form of abuse or neglect but also early malnutrition or an early immune challenge elicit very similar long-term effects on brain structure and function. During early-life, both exogenous factors like nutrition and maternal care, as well as endogenous modulators, including stress hormones and mediator of immunological activity affect brain development. The interplay of these key elements and their underlying molecular mechanisms are not fully understood. We discuss here the hypothesis that exposure to early-life adversity (specifically stress, under/malnutrition and infection) leads to life-long alterations in hippocampal-related cognitive functions, at least partly via changes in hippocampal neurogenesis. We further discuss how these different key elements of the early-life environment interact and affect one another and suggest that it is a synergistic action of these elements that shapes cognition throughout life. Finally, we consider different intervention studies aiming to prevent these early-life adversity induced consequences. The emerging evidence for the intriguing interplay of stress, nutrition, and immune activity in the early-life programming calls for a more in depth understanding of the interaction of these elements and the underlying mechanisms. This knowledge will help to develop intervention strategies that will converge on a more complete set of changes induced by early-life adversity.

  10. Low-grade disease activity in early life precedes childhood asthma and allergy.

    PubMed

    Chawes, Bo Lund Krogsgaard

    2016-08-01

    Asthma and allergies are today the most common chronic diseases in children and the leading causes of school absences, chronic medication usage, emergency department visits and hospitalizations, which affect all members of the family and represent a significant societal and scientific challenge. These highly prevalent disorders are thought to originate from immune distortion in early childhood, but the etiology and heterogeneity of the disease mechanisms are not understood, which hampers preventive initiatives and makes treatment inadequate. The objective of this thesis is to investigate the presence of an early life disease activity prior to clinical symptoms to understand the anteceding pathophysiological steps towards childhood asthma and allergy. The thesis is built on seven studies from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2000) birth cohort examining biomarkers of disease activity in 411 asymptomatic neonates in cord blood (I-II), urine (III), exhaled breath (IV-V) and infant lung function (VI-VII) in relation to the subsequent development of asthma and allergy during the first seven years of life. In papers I-II, we studied cord blood chemokines and 25(OH)-vitamin D, which represent a proxy of the inborn immature immune system, the intrauterine milieu, and the maternal immune health during pregnancy. High levels of the Th2-related chemokine CCL22 and high CCL22/CXCL11 ratio were positively correlated with total IgE level during preschool age (II). This suggests an inborn Th2 skewing of the immune system in healthy newborns subsequently developing elevated total IgE antibodies, which is considered to increase the risk of asthma and allergies later in life. Additionally, deficient cord blood 25(OH)-vitamin D levels were associated with a 2.7-fold increased risk of recurrent wheeze at age 0-7 years (I). Together, these findings support the concept that early life immune programming in the pre-symptomatic era plays an essential role

  11. Oestradiol Exposure Early in Life Programs Daily and Circadian Activity Rhythms in Adult Mice.

    PubMed

    Royston, S E; Bunick, D; Mahoney, M M

    2016-01-01

    Hormone signalling during critical periods organises the adult circadian timekeeping system by altering adult hormone sensitivity and shaping fundamental properties of circadian rhythmicity. However, the timing of when developmental oestrogens modify the timekeeping system is poorly understood. To test the hypothesis that alterations in postnatal oestrogenic signalling organise adult daily activity rhythms, we utilised aromatase knockout mice (ArKO), which lack the enzyme required for oestradiol synthesis. ArKO and wild-type (WT) males and females were administered either oestradiol (E) or oil (OIL) daily for the first 5 postnatal days (p1-5E and p1-5OIL , respectively) because this time encompasses the emergence of clock gene rhythmicity and light responsiveness in the suprachiasmatic nucleus, a bilateral hypothalamic structure regarded as the 'master oscillator'. After sexual maturation, gonadectomy and exogenous oestradiol supplementation, locomotor parameters were assessed. We determined that altered oestrogenic signalling in early life exerts organisational control over the expression of daily and circadian activity rhythms in adult mice. Specifically, p1-5E reduced total wheel running activity in male and female ArKO and female WT mice but had no effect on WT male activity levels. In females, wheel running was consolidated by p1-5E to the early versus late evening, a phenomenon characteristic of male mice. The time of peak activity was advanced by p1-5E in WT and ArKO females but not males. P1-5E shortened the length of the active phase (alpha) in WT males but had no effect on ArKO males or females of either genotypes. Finally, p1-5E altered the magnitude of photic-induced shifts, suggesting that developmental oestrogenic signalling impacts adult circadian functions. In the present study, we further define both a critical period of development of the adult timekeeping system and the role that oestrogenic signalling plays in the expression of daily and

  12. HEART--the Hounslow Early Active Recovery Team: implementing an inclusive strength-based model of care for people with early psychosis.

    PubMed

    Kelly, J; Wellman, N; Sin, J

    2009-08-01

    In recent years in the UK, the National Health Service has made policy commitments to delivering mental health services based on recovery principles. In general though, the UK mental health service providers are in the early stages of implementing recovery principles and approaches in front-line services. This paper describes the work of the Hounslow Early Active Recovery Team (HEART), which has made substantial progress in placing recovery principles and approaches at the heart of the work of an early intervention for psychosis team working in an ethnically diverse area of West London. As evidence of the success of the HEART, in its first year and half, the team has achieved high levels of customer satisfaction with its work and a recent audit has revealed that 57% of respondents were in employment or education contrasting with the extremely high unemployment rates reported in several UK studies of people with serious mental health problems.

  13. Low-grade disease activity in early life precedes childhood asthma and allergy.

    PubMed

    Chawes, Bo Lund Krogsgaard

    2016-08-01

    Asthma and allergies are today the most common chronic diseases in children and the leading causes of school absences, chronic medication usage, emergency department visits and hospitalizations, which affect all members of the family and represent a significant societal and scientific challenge. These highly prevalent disorders are thought to originate from immune distortion in early childhood, but the etiology and heterogeneity of the disease mechanisms are not understood, which hampers preventive initiatives and makes treatment inadequate. The objective of this thesis is to investigate the presence of an early life disease activity prior to clinical symptoms to understand the anteceding pathophysiological steps towards childhood asthma and allergy. The thesis is built on seven studies from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2000) birth cohort examining biomarkers of disease activity in 411 asymptomatic neonates in cord blood (I-II), urine (III), exhaled breath (IV-V) and infant lung function (VI-VII) in relation to the subsequent development of asthma and allergy during the first seven years of life. In papers I-II, we studied cord blood chemokines and 25(OH)-vitamin D, which represent a proxy of the inborn immature immune system, the intrauterine milieu, and the maternal immune health during pregnancy. High levels of the Th2-related chemokine CCL22 and high CCL22/CXCL11 ratio were positively correlated with total IgE level during preschool age (II). This suggests an inborn Th2 skewing of the immune system in healthy newborns subsequently developing elevated total IgE antibodies, which is considered to increase the risk of asthma and allergies later in life. Additionally, deficient cord blood 25(OH)-vitamin D levels were associated with a 2.7-fold increased risk of recurrent wheeze at age 0-7 years (I). Together, these findings support the concept that early life immune programming in the pre-symptomatic era plays an essential role

  14. C-H Bond Activation by Early Transition Metal Carbide Cluster Anion MoC3 (-).

    PubMed

    Li, Zi-Yu; Hu, Lianrui; Liu, Qing-Yu; Ning, Chuan-Gang; Chen, Hui; He, Sheng-Gui; Yao, Jiannian

    2015-12-01

    Although early transition metal (ETM) carbides can activate CH bonds in condensed-phase systems, the electronic-level mechanism is unclear. Atomic clusters are ideal model systems for understanding the mechanisms of bond activation. For the first time, CH activation of a simple alkane (ethane) by an ETM carbide cluster anion (MoC3 (-) ) under thermal-collision conditions has been identified by using high-resolution mass spectrometry, photoelectron imaging spectroscopy, and high-level quantum chemical calculations. Dehydrogenation and ethene elimination were observed in the reaction of MoC3 (-) with C2 H6 . The CH activation follows a mechanism of oxidative addition that is much more favorable in the carbon-stabilized low-spin ground electronic state than in the high-spin excited state. The reaction efficiency between the MoC3 (-) anion and C2 H6 is low (0.23±0.05) %. A comparison between the anionic and a highly efficient cationic reaction system (Pt(+) +C2 H6 ) was made. It turned out that the potential-energy surfaces for the entrance channels of the anionic and cationic reaction systems can be very different. PMID:26490554

  15. Vestibular activation differentially modulates human early visual cortex and V5/MT excitability and response entropy.

    PubMed

    Seemungal, Barry M; Guzman-Lopez, Jessica; Arshad, Qadeer; Schultz, Simon R; Walsh, Vincent; Yousif, Nada

    2013-01-01

    Head movement imposes the additional burdens on the visual system of maintaining visual acuity and determining the origin of retinal image motion (i.e., self-motion vs. object-motion). Although maintaining visual acuity during self-motion is effected by minimizing retinal slip via the brainstem vestibular-ocular reflex, higher order visuovestibular mechanisms also contribute. Disambiguating self-motion versus object-motion also invokes higher order mechanisms, and a cortical visuovestibular reciprocal antagonism is propounded. Hence, one prediction is of a vestibular modulation of visual cortical excitability and indirect measures have variously suggested none, focal or global effects of activation or suppression in human visual cortex. Using transcranial magnetic stimulation-induced phosphenes to probe cortical excitability, we observed decreased V5/MT excitability versus increased early visual cortex (EVC) excitability, during vestibular activation. In order to exclude nonspecific effects (e.g., arousal) on cortical excitability, response specificity was assessed using information theory, specifically response entropy. Vestibular activation significantly modulated phosphene response entropy for V5/MT but not EVC, implying a specific vestibular effect on V5/MT responses. This is the first demonstration that vestibular activation modulates human visual cortex excitability. Furthermore, using information theory, not previously used in phosphene response analysis, we could distinguish between a specific vestibular modulation of V5/MT excitability from a nonspecific effect at EVC.

  16. Low Dose Nicotine Attenuates Aβ Neurotoxicity through Activation Early Growth Response Gene 1 Pathway

    PubMed Central

    Zhang, Jie; Qiu, Jinhua; Du, Guicheng; Qiao, Zhiliang; Jin, Guanghui; Gao, Fengguang; Zhang, Qiqing

    2015-01-01

    Epidemiological studies indicate that smoking is negatively correlated with the incidence and development of Alzheimer's disease (AD). Nicotine was reported to be the active factor. However, the detailed mechanisms still remain to be fully elucidated. Early growth response gene 1 (EGR-1) plays important roles in several important biological processes such as promoting cell growth, differentiation, anti oxidative stress, and apoptosis, but few in the pathogenesis of AD. In the present study, we show that nicotine can activate the MAPK/ERK/EGR-1 signaling pathway partially through α7 nAChR. In addition, the up-regulation of EGR-1 by nicotine can also increase the phosphorylation of CyclinD1 which contributes to the attenuation of amyloid-β (Aβ25–35) -induced neurotoxicity. Although nicotine and Aβ25–35 can activate EGR-1, the expression of EGR-1 is down-regulated following treatment with nicotine and Aβ25–35. This study demonstrates that low dose nicotine attenuates Aβ25–35-induced neurotoxicity in vitro and in vivo through activating EGR-1 pathway. PMID:25815723

  17. Mast cell activation and neutrophil recruitment promotes early and robust inflammation in the meninges in EAE.

    PubMed

    Christy, Alison L; Walker, Margaret E; Hessner, Martin J; Brown, Melissa A

    2013-05-01

    The meninges are often considered inert tissues that house the CSF and provide protection for the brain and spinal cord. Yet emerging data demonstrates that they are also active sites of immune responses. Furthermore, the blood-CSF barrier surrounding meningeal blood vessels, together with the blood-brain barrier (BBB), is postulated to serve as a gateway for the pathological infiltration of immune cells into the CNS in multiple sclerosis (MS). Our previous studies using mast cell-deficient (Kit(W/Wv)) mice demonstrated that mast cells resident in the dura mater and pia mater exacerbate experimental autoimmune encephalomyelitis (EAE), a rodent model of MS, by facilitating CNS inflammatory cell influx. Here we examined the underlying mechanisms that mediate these effects. We demonstrate that there are dramatic alterations in immune associated gene expression in the meninges in pre-clinical disease, including those associated with mast cell and neutrophil function. Meningeal mast cells are activated within 24 h of disease induction, but do not directly compromise CNS vascular integrity. Rather, through production of TNF, mast cells elicit an early influx of neutrophils, cells known to alter vascular permeability, into the meninges. These data add to the growing evidence that inflammation in the meninges precedes CNS immune cell infiltration and establish that mast cells are among the earliest participants in these disease-initiating events. We hypothesize that mast cell-dependent neutrophil recruitment and activation in the meninges promotes early breakdown of the local BBB and CSF-blood barrier allowing initial immune cell access to the CNS.

  18. Dentin caries activity in early occlusal lesions selected to receive operative treatment

    PubMed Central

    Lehmann, Maryann; Veitz-Keenan, Analia; Matthews, Abigail G.; Vena, Donald; Grill, Ashley; Craig, Ronald G.; Curro, Frederick A.; Thompson, Van P.

    2014-01-01

    Background Members of the practice-based research network Practitioners Engaged in Applied Research and Learning (PEARL) Network investigated the dentin caries activity in early occlusal lesions and its relationship to patient age, preoperative tooth sensitivity and radio-graphic appearance, as well as its influence on preparation depth and volume. Methods PEARL Network practitioner-investigators (P-Is) (n = 45), general dentists who were trained but whose methods were not calibrated, conducted a study regarding postoperative hypersensitivity in resin-based composite restorations. The P-Is enrolled as study participants 613 patients with occlusal carious lesions that, in the P-Is’ clinical judgment, required restoration. The P-Is used baseline radiographs to assess the depth and extent of the lesions. Data for 671 restorations included baseline sensitivity; ranking of dentin caries activity on the opening of the enamel; radiographic visibility (n = 652); and measurements of preparation depth, width and length. Results P-Is found rapidly progressing dentin caries in 38.5 percent (258 of 671) of lesions and slowly progressing (and potentially inactive dentin) caries in the remainder of the lesions. Rapidly progressing caries was not related to the participant’s age or participant-reported preoperative hypersensitivity but was related to the lesion depth as seen radiographically (P < .001) and depth (P < .001) and volume (P < .001) of the preparation. Molars had slightly higher but not statistically significant levels of caries activity. Conclusion Rapidly progressing dentin caries, while present in only 38.5 percent of lesions, was related to the lesion’s radiographic appearance but not to the participant’s age or the study tooth’s pre-operative sensitivity. Clinical Implications On the basis of the low level of rapidly progressing dentin caries in this study population and the fact that slowly progressing caries can be inactive or remineralizing, the

  19. Inhibition of protein kinase B activity induces cell cycle arrest and apoptosis during early G₁ phase in CHO cells.

    PubMed

    van Opstal, Angélique; Bijvelt, José; van Donselaar, Elly; Humbel, Bruno M; Boonstra, Johannes

    2012-04-01

    Inhibition of PKB (protein kinase B) activity using a highly selective PKB inhibitor resulted in inhibition of cell cycle progression only if cells were in early G1 phase at the time of addition of the inhibitor, as demonstrated by time-lapse cinematography. Addition of the inhibitor during mitosis up to 2 h after mitosis resulted in arrest of the cells in early G1 phase, as deduced from the expression of cyclins D and A and incorporation of thymidine. After 24 h of cell cycle arrest, cells expressed the cleaved caspase-3, a central mediator of apoptosis. These results demonstrate that PKB activity in early G1 phase is required to prevent the induction of apoptosis. Using antibodies, it was demonstrated that active PKB translocates to the nucleus during early G1 phase, while an even distribution of PKB was observed through cytoplasm and nucleus during the end of G1 phase. PMID:22251027

  20. Transcriptional activation is a conserved feature of the early embryonic factor Zelda that requires a cluster of four zinc fingers for DNA binding and a low-complexity activation domain.

    PubMed

    Hamm, Danielle C; Bondra, Eliana R; Harrison, Melissa M

    2015-02-01

    Delayed transcriptional activation of the zygotic genome is a nearly universal phenomenon in metazoans. Immediately following fertilization, development is controlled by maternally deposited products, and it is not until later stages that widespread activation of the zygotic genome occurs. Although the mechanisms driving this genome activation are currently unknown, the transcriptional activator Zelda (ZLD) has been shown to be instrumental in driving this process in Drosophila melanogaster. Here we define functional domains of ZLD required for both DNA binding and transcriptional activation. We show that the C-terminal cluster of four zinc fingers mediates binding to TAGteam DNA elements in the promoters of early expressed genes. All four zinc fingers are required for this activity, and splice isoforms lacking three of the four zinc fingers fail to activate transcription. These truncated splice isoforms dominantly suppress activation by the full-length, embryonically expressed isoform. We map the transcriptional activation domain of ZLD to a central region characterized by low complexity. Despite relatively little sequence conservation within this domain, ZLD orthologs from Drosophila virilis, Anopheles gambiae, and Nasonia vitripennis activate transcription in D. melanogaster cells. Transcriptional activation by these ZLD orthologs suggests that ZLD functions through conserved interactions with a protein cofactor(s). We have identified distinct DNA-binding and activation domains within the critical transcription factor ZLD that controls the initial activation of the zygotic genome.

  1. The role of early neural activity in the maturation of turtle retinal function.

    PubMed

    Sernagor, E; Mehta, V

    2001-10-01

    In the developing vertebrate retina, ganglion cells fire spontaneous bursts of action potentials long before the eye becomes exposed to sensory experience at birth. These early bursts are synchronised between neighbouring retinal ganglion cells (RGCs), yielding unique spatiotemporal patterns: 'waves' of activity sweep across large retinal areas every few minutes. Both at retinal and extraretinal levels, these embryonic retinal waves are believed to guide the wiring of the visual system using hebbian mechanisms of synaptic strengthening. In the first part of this review, we recapitulate the evidence for a role of these embryonic spontaneous bursts of activity in shaping developing complex receptive field properties of RGCs in the turtle embryonic retina. We also discuss the role of visual experience in establishing RGC visual functions, and how spontaneous activity and visual experience interact to bring developing receptive fields to maturation. We have hypothesised that the physiological changes associated with development reflect modifications in the dendritic arbours of RGCs, the anatomical substrate of their receptive fields. We demonstrate that there is a temporal correlation between the period of receptive field expansion and that of dendritic growth. Moreover, the immature spontaneous activity contributes to dendritic growth in developing RGCs. Intracellular staining of RGCs reveals, however, that immature receptive fields only rarely show direct correlation with the layout of the corresponding dendritic tree. To investigate the possibility that not only the presence of the spontaneous activity, but even the precise spatiotemporal patterns encoded in retinal waves might contribute to the refinement of retinal neural circuitry, first we must clarify the mechanisms mediating the generation and propagation of these waves across development. In the second part of this review, we present evidence that turtle retinal waves, visualised using calcium imaging

  2. Activation of heat shock gene transcription by heat shock factor 1 involves oligomerization, acquisition of DNA-binding activity, and nuclear localization and can occur in the absence of stress.

    PubMed Central

    Sarge, K D; Murphy, S P; Morimoto, R I

    1993-01-01

    The existence of multiple heat shock factor (HSF) genes in higher eukaryotes has promoted questions regarding the functions of these HSF family members, especially with respect to the stress response. To address these questions, we have used polyclonal antisera raised against mouse HSF1 and HSF2 to examine the biochemical, physical, and functional properties of these two factors in unstressed and heat-shocked mouse and human cells. We have identified HSF1 as the mediator of stress-induced heat shock gene transcription. HSF1 displays stress-induced DNA-binding activity, oligomerization, and nuclear localization, while HSF2 does not. Also, HSF1 undergoes phosphorylation in cells exposed to heat or cadmium sulfate but not in cells treated with the amino acid analog L-azetidine-2-carboxylic acid, indicating that phosphorylation of HSF1 is not essential for its activation. Interestingly, HSF1 and HSF2 overexpressed in transfected 3T3 cells both display constitutive DNA-binding activity, oligomerization, and transcriptional activity. These results demonstrate that HSF1 can be activated in the absence of physiological stress and also provide support for a model of regulation of HSF1 and HSF2 activity by a titratable negative regulatory factor. Images PMID:8441385

  3. Functional changes in digestive enzyme activities of meagre (Argyrosomus regius; Asso, 1801) during early ontogeny.

    PubMed

    Suzer, Cüneyt; Kamacı, H Okan; Çoban, Deniz; Yıldırım, Şükrü; Fırat, Kürşat; Saka, Şahin

    2013-08-01

    The ontogenesis of main pancreatic and intestinal enzymes was investigated in the recent promising Mediterranean candidate species of meagre, Argyrosomus regius, during larval development until 40 days after hatching (DAH). The green-water technique was carried out for larval rearing. Whole-body homogenates were used for enzymatic analysis in larvae younger than 15 DAH; after this date, older larvae were dissected into two segments as pancreatic and intestinal segment. Trypsin was detected as early as hatching and sharply increased concurrently with age and exogenous feeding 15 DAH, but constant decline was observed until the end of experiment. Amylase was determined at 2 DAH and sharply increased 10 DAH. Then, slight decreases were found between 10 and 15 DAH, and then slow alterations were continued until the end of the experiment. Lipase was firstly measured on day 3; then, sudden decline was observed between 20 and 25 DAH. After this date, slow fluctuations were maintained until the end of the experiment. Pepsin was firstly assayed 15 DAH related to gastric gland secretion and sharply increased 30 DAH. Then, it slowly varied until end of the experiment. Enzymes of brush border membranes, alkaline phosphatase and aminopeptidase N showed similar pattern on specific activities during the first 10 days. Thereafter, while specific activity of alkaline phosphatase slightly decreased 15 and fluctuated until 20 DAH, aminopeptidase N activity slowly increased 20 DAH. Then, activity of alkaline phosphatase and aminopeptidase N constantly increased 30 DAH, indicating maturation of the intestinal digestive process, and also, these activities continued to slowly increase until the end of the experiment. The specific activity of cytosolic peptidase, leucine-alanine peptidase, smoothly increased on day 8, then fluctuated until 15 DAH. After this date, in contrast to enzymes of brush border membranes, it sharply decreased 25 DAH and continued to gradually decline until the end

  4. Jasmonate signaling is activated in the very early stages of iron deficiency responses in rice roots.

    PubMed

    Kobayashi, Takanori; Itai, Reiko Nakanishi; Senoura, Takeshi; Oikawa, Takaya; Ishimaru, Yasuhiro; Ueda, Minoru; Nakanishi, Hiromi; Nishizawa, Naoko K

    2016-07-01

    Under low iron availability, plants induce the expression of various genes involved in iron uptake and translocation at the transcriptional level. This iron deficiency response is affected by various plant hormones, but the roles of jasmonates in this response are not well-known. We investigated the involvement of jasmonates in rice iron deficiency responses. High rates of jasmonate-inducible genes were induced during the very early stages of iron deficiency treatment in rice roots. Many jasmonate-inducible genes were also negatively regulated by the ubiquitin ligases OsHRZ1 and OsHRZ2 and positively regulated by the transcription factor IDEF1. Ten out of 35 genes involved in jasmonate biosynthesis and signaling were rapidly induced at 3 h of iron deficiency treatment, and this induction preceded that of known iron deficiency-inducible genes involved in iron uptake and translocation. Twelve genes involved in jasmonate biosynthesis and signaling were also upregulated in HRZ-knockdown roots. Endogenous concentrations of jasmonic acid and jasmonoyl isoleucine tended to be rapidly increased in roots in response to iron deficiency treatment, whereas these concentrations were higher in HRZ-knockdown roots under iron-sufficient conditions. Analysis of the jasmonate-deficient cpm2 mutant revealed that jasmonates repress the expression of many iron deficiency-inducible genes involved in iron uptake and translocation under iron sufficiency, but this repression is partly canceled under an early stage of iron deficiency. These results indicate that jasmonate signaling is activated during the very early stages of iron deficiency, which is partly regulated by IDEF1 and OsHRZs.

  5. Early Detection of Physical Activity for People With Type 1 Diabetes Mellitus

    PubMed Central

    Dasanayake, Isuru S.; Bevier, Wendy C.; Castorino, Kristin; Pinsker, Jordan E.; Seborg, Dale E.; Doyle, Francis J.; Dassau, Eyal

    2015-01-01

    Background: Early detection of exercise in individuals with type 1 diabetes mellitus (T1DM) may allow changes in therapy to prevent hypoglycemia. Currently there is limited experience with automated methods that detect the onset and end of exercise in this population. We sought to develop a novel method to quickly and reliably detect the onset and end of exercise in these individuals before significant changes in blood glucose (BG) occur. Methods: Sixteen adults with T1DM were studied as outpatients using a diary, accelerometer, heart rate monitor, and continuous glucose monitor for 2 days. These data were used to develop a principal component analysis based exercise detection method. Subjects also performed 60 and 30 minute exercise sessions at 30% and 50% predicted heart rate reserve (HRR), respectively. The detection method was applied to the exercise sessions to determine how quickly the detection of start and end of exercise occurred relative to change in BG. Results: Mild 30% HRR and moderate 50% HRR exercise onset was identified in 6 ± 3 and 5 ± 2 (mean ± SD) minutes, while completion was detected in 3 ± 8 and 6 ± 5 minutes, respectively. BG change from start of exercise to detection time was 1 ± 6 and −1 ± 3 mg/dL, and, from the end of exercise to detection time was 6 ± 4 and −17 ± 13 mg/dL, respectively, for the 2 exercise sessions. False positive and negative ratios were 4 ± 2% and 21 ± 22%. Conclusions: The novel method for exercise detection identified the onset and end of exercise in approximately 5 minutes, with an average BG change of only −6 mg/dL. PMID:26134831

  6. Plasminogen activator inhibitor-1 as an early potential diagnostic marker for Alzheimer's disease.

    PubMed

    Oh, Jaeho; Lee, Hye-Ja; Song, Ji-Hyun; Park, Sang Ick; Kim, Hyunyoung

    2014-12-01

    Alzheimer's disease (AD) is the most common cause of dementia in individuals over 65 years old. However, to date, no useful early diagnostic markers for AD have been discovered. We examined the utility of plasminogen activator inhibitor-1 (PAI-1) as a potential biomarker for AD in subjects with mild cognitive impairment (MCI) or AD, as well as in nondemented healthy controls. Plasma PAI-1 levels were measured by enzyme-linked immunosorbent assays (ELISAs) in samples collected from 76 patients with MCI, 74 patients with AD, and 76 healthy controls. Our results show that plasma PAI-1 levels gradually increased as dementia progressed. The mean levels of plasma PAI-1 in patients with MCI and AD patients were significantly higher than those of in healthy controls. Consistently, neuropsychological examination (e.g., MMSE, CDR) also demonstrated significant correlations between the plasma PAI-1 levels and cognitive function. In conclusion, the level of plasma PAI-1 is a potential biomarker for the early detection and diagnosis of AD.

  7. The NASA Soil Moisture Active Passive (SMAP) Mission Status and Early Results

    NASA Astrophysics Data System (ADS)

    Entekhabi, D.; Yueh, S. H.; O'Neill, P. E.; Entin, J. K.; Njoku, E. G.; Kellogg, K.

    2015-12-01

    NASA's Soil Moisture Active Passive (SMAP) mission was launched on January 31, 2015. SMAP provides high-resolution, frequent revisit global mapping of soil moisture and freeze/thaw state based on coincident L-band radiometer and L-band radar measurements. The primary science goal of SMAP is to provide new perspectives on how the three fundamental cycles of the Earth system, the water, energy and carbon cycles, are linked together over land. Soil moisture is the key variable that links the three cycles and makes their co-variations synchronous in time. Soil moisture products with varying resolution and coverage are produced from the radiometer alone, radar alone, radiometer-radar combination and data assimilation. In this session the status of the SMAP observatory and early results based on the science data products will be included. The science data acquisition began in May 2015 following several weeks of observatory and instrument commissioning. An intense calibration and validation period followed. Preliminary science products on instrument measurements, soil moisture, landscape frozen or thawed status, and net ecosystem exchange are available at publicly-accessible data archives. The presentation will include early and summary results on the validation of these products. The instrument measurements can also be used to map sea-ice coverage, ocean surface winds and sea surface salinity. Examples of these global retrievals are also presented.

  8. Early Solar System hydrothermal activity in chondritic asteroids on 1-10-year timescales.

    PubMed

    Dyl, Kathryn A; Bischoff, Addi; Ziegler, Karen; Young, Edward D; Wimmer, Karl; Bland, Phil A

    2012-11-01

    Chondritic meteorites are considered the most primitive remnants of planetesimals from the early Solar System. As undifferentiated objects, they also display widespread evidence of water-rock interaction on the parent body. Understanding this history has implications for the formation of planetary bodies, the delivery of water to the inner Solar System, and the formation of prebiotic molecules. The timescales of water-rock reactions in these early objects, however, are largely unknown. Here, we report evidence for short-lived water-rock reactions in the highly metamorphosed ordinary chondrite breccia Villalbeto de la Peña (L6). An exotic clast (d = 2cm) has coexisting variations in feldspar composition and oxygen isotope ratios that can only result from hydrothermal conditions. The profiles were modeled at T = 800 °C and P(H(2)O) = 1 bar using modified grain-boundary diffusion parameters for oxygen self-diffusion and reaction rates of NaSiCa(-1)Al(-1) exchange in a fumarole. The geochemical data are consistent with hydrothermal activity on the parent body lasting only 1-10 y. This result has wide-ranging implications for the geological history of chondritic asteroids.

  9. Early Solar System hydrothermal activity in chondritic asteroids on 1–10-year timescales

    PubMed Central

    Dyl, Kathryn A.; Bischoff, Addi; Ziegler, Karen; Young, Edward D.; Wimmer, Karl; Bland, Phil A.

    2012-01-01

    Chondritic meteorites are considered the most primitive remnants of planetesimals from the early Solar System. As undifferentiated objects, they also display widespread evidence of water–rock interaction on the parent body. Understanding this history has implications for the formation of planetary bodies, the delivery of water to the inner Solar System, and the formation of prebiotic molecules. The timescales of water–rock reactions in these early objects, however, are largely unknown. Here, we report evidence for short-lived water–rock reactions in the highly metamorphosed ordinary chondrite breccia Villalbeto de la Peña (L6). An exotic clast (d = 2cm) has coexisting variations in feldspar composition and oxygen isotope ratios that can only result from hydrothermal conditions. The profiles were modeled at T = 800 °C and P(H2O) = 1 bar using modified grain-boundary diffusion parameters for oxygen self-diffusion and reaction rates of NaSiCa-1Al-1 exchange in a fumarole. The geochemical data are consistent with hydrothermal activity on the parent body lasting only 1–10 y. This result has wide-ranging implications for the geological history of chondritic asteroids. PMID:23093668

  10. Early motor skill competence as a mediator of child and adult physical activity

    PubMed Central

    Loprinzi, Paul D.; Davis, Robert E.; Fu, Yang-Chieh

    2015-01-01

    Objective: In order to effectively promote physical activity (PA) during childhood, and across the lifespan, a better understanding of the role of early motor skill development on child and adult PA is needed. Methods: Here, we propose a conceptual model delineating the hypothesized influence of motor skill development on child and adult PA, while providing an overview of the current empirical research related to this model. Results: There is consistent and emerging evidence showing that adequate motor skill competence, particularly locomotor and gross motor skills, is associated with increased PA levels during the preschool, child, and adolescent years, with early motor skill development also influencing enjoyment of PA as well as long-term PA and motor skill performance. The physical education setting appears to be a well-suited environment for motor skill development. Conclusion: Employing appropriate strategies to target motor skill development across the childhood years is of paramount interest in helping shape children's PA behavior, their experiences related to PA, as well as maintain their PA. PMID:26844157

  11. Early clinical development of anti-tuberculosis drugs: science, statistics and sterilizing activity.

    PubMed

    Davies, Geraint R

    2010-05-01

    Controversy continues over how best to capture "sterilizing activity" of anti-tuberculosis regimens in early clinical development. Selecting surrogate endpoints capable of providing proof-of-concept, finding the optimal dose and identifying the best combination of companion drugs for new agents currently depends on an empirical balance of favourable biological, logistical and statistical properties. While more flexible rate-based measures of treatment response are better suited to these tasks, their interpretation depends critically on understanding the laboratory techniques on which they are based. In order to reduce the costly uncertainties of Phase II and III development, more extensive evaluation of such surrogate endpoints will be required in broader-based collaborative studies which make better use of our emerging scientific knowledge of the underlying mechanisms of sterilization in a clinical context.

  12. Improving human activity recognition and its application in early stroke diagnosis.

    PubMed

    Villar, José R; González, Silvia; Sedano, Javier; Chira, Camelia; Trejo-Gabriel-Galan, Jose M

    2015-06-01

    The development of efficient stroke-detection methods is of significant importance in today's society due to the effects and impact of stroke on health and economy worldwide. This study focuses on Human Activity Recognition (HAR), which is a key component in developing an early stroke-diagnosis tool. An overview of the proposed global approach able to discriminate normal resting from stroke-related paralysis is detailed. The main contributions include an extension of the Genetic Fuzzy Finite State Machine (GFFSM) method and a new hybrid feature selection (FS) algorithm involving Principal Component Analysis (PCA) and a voting scheme putting the cross-validation results together. Experimental results show that the proposed approach is a well-performing HAR tool that can be successfully embedded in devices.

  13. Active-sterile neutrino oscillations in the early Universe with full collision terms

    SciTech Connect

    Hannestad, Steen; Hansen, Rasmus Sloth; Tram, Thomas; Wong, Yvonne Y.Y. E-mail: rshansen@phys.au.dk E-mail: yvonne.y.wong@unsw.edu.au

    2015-08-01

    Sterile neutrinos are thermalised in the early Universe via oscillations with the active neutrinos for certain mixing parameters. The most detailed calculation of this thermalisation process involves the solution of the momentum-dependent quantum kinetic equations, which track the evolution of the neutrino phase space distributions. Until now the collision terms in the quantum kinetic equations have always been approximated using equilibrium distributions, but this approximation has never been checked numerically. In this work we revisit the sterile neutrino thermalisation calculation using the full collision term, and compare the results with various existing approximations in the literature. We find a better agreement than would naively be expected, but also identify some issues with these approximations that have not been appreciated previously. These include an unphysical production of neutrinos via scattering and the importance of redistributing momentum through scattering, as well as details of Pauli blocking. Finally, we devise a new approximation scheme, which improves upon some of the shortcomings of previous schemes.

  14. Active-sterile neutrino oscillations in the early Universe with full collision terms

    SciTech Connect

    Hannestad, Steen; Hansen, Rasmus Sloth; Tram, Thomas; Wong, Yvonne Y.Y.

    2015-08-11

    Sterile neutrinos are thermalised in the early Universe via oscillations with the active neutrinos for certain mixing parameters. The most detailed calculation of this thermalisation process involves the solution of the momentum-dependent quantum kinetic equations, which track the evolution of the neutrino phase space distributions. Until now the collision terms in the quantum kinetic equations have always been approximated using equilibrium distributions, but this approximation has never been checked numerically. In this work we revisit the sterile neutrino thermalisation calculation using the full collision term, and compare the results with various existing approximations in the literature. We find a better agreement than would naively be expected, but also identify some issues with these approximations that have not been appreciated previously. These include an unphysical production of neutrinos via scattering and the importance of redistributing momentum through scattering, as well as details of Pauli blocking. Finally, we devise a new approximation scheme, which improves upon some of the shortcomings of previous schemes.

  15. Emergency department syndromic surveillance providing early warning of seasonal respiratory activity in England.

    PubMed

    Hughes, H E; Morbey, R; Hughes, T C; Locker, T E; Pebody, R; Green, H K; Ellis, J; Smith, G E; Elliot, A J

    2016-04-01

    Seasonal respiratory infections place an increased burden on health services annually. We used a sentinel emergency department syndromic surveillance system to understand the factors driving respiratory attendances at emergency departments (EDs) in England. Trends in different respiratory indicators were observed to peak at different points during winter, with further variation observed in the distribution of attendances by age. Multiple linear regression analysis revealed acute respiratory infection and bronchitis/bronchiolitis ED attendances in patients aged 1-4 years were particularly sensitive indicators for increasing respiratory syncytial virus activity. Using near real-time surveillance of respiratory ED attendances may provide early warning of increased winter pressures in EDs, particularly driven by seasonal pathogens. This surveillance may provide additional intelligence about different categories of attendance, highlighting pressures in particular age groups, thereby aiding planning and preparation to respond to acute changes in EDs, and thus the health service in general.

  16. Chaos, determinacy and fractals in active-sterile neutrino oscillations in the early universe

    SciTech Connect

    Abazajian, Kevork N; Agrawal, Prateek E-mail: apr@umd.edu

    2008-10-15

    The possibility of light sterile neutrinos allows for the resonant production of lepton number in the early universe through matter-affected neutrino mixing. For a given mixing of the active and sterile neutrino states it has been found that the lepton number generation process is chaotic and strongly oscillatory. We undertake a new study of the sensitivity of this process to initial conditions through the quantum rate equations. We confirm the chaoticity of the process in this solution, and moreover find that the resultant lepton number and the sign of the asymmetry produce a fractal in the parameter space of mass, mixing angle and initial baryon number. This has implications for future searches for sterile neutrinos, where arbitrarily high sensitivity may not be determinate in forecasting the lepton number of the universe.

  17. Primary patellar tendon repair and early mobilization: results in an active-duty population.

    PubMed

    Enad, J G; Loomis, L L

    2001-01-01

    We retrospectively reviewed 13 patellar tendon repairs done over 32 months at a tertiary care, military medical center. Early mobilization was initiated within 2 weeks postoperatively. Clinical and functional results were statistically examined with relation to age, timing of surgery, length of follow-up, quadriceps atrophy, extensor lag, patella position, and time to full duty. At an average of 24 months' follow-up, six patients (46%) had thigh girth atrophy, and one patient (8%) had an extensor lag >5 degrees. Mean Lysholm score was 84 (range, 57 to 100). Maximum postoperative Tegner activity scores averaged 7.1 (range, 5 to 10). Clinical results classified five cases as excellent, three good, three fair, and two poor. Functional results classified three cases as excellent, four good, two fair, and four poor. Time to return to duty averaged 13 months. Our results suggest that adequate extensor function can be restored after primary repair and immediate motion therapy.

  18. The plasmacytoma J558L lacks constitutively active NF-kappa B and is deficient in early response gene activation.

    PubMed

    Anderson, M T; Wims, L A; Morrison, S L

    1991-12-01

    In mature B cells the nuclear factor NF-kappa B which binds within the kappa enhancer is constitutively present in the nucleus. However, the lambda light chain producing myeloma J558L has been found to lack constitutively functional NF-kappa B. Deoxycholate released functional NF-kappa B from cytoplasmic extracts and functional NF-kappa B was present in J558L following cycloheximide but not phorbol ester treatment. J558L was also unable to respond to phorbol ester stimulation with synthesis of mRNA from the early response gene TIS11. J558L differs from S107, another myeloma which was found to be deficient in the synthesis of NF-kappa B but not in the activation of TIS11. Somatic cell hybrids were used to further define the defect in J558L; hybrids were made with the myelomas S107 and S194 and the pre-B cell line 70Z/3. In general, complementation of the defect in J558L was observed; however there was not a direct correlation between the levels of TIS11 mRNA and NF-kappa B expression in the somatic cell hybrids, suggesting that the pathways of activation of these genes, while possibly sharing common elements, are not identical. The defect in J558L was surprising given that it has frequently been used for the expression of transfected light chain genes.

  19. Early reduction in toe flexor strength is associated with physical activity in elderly men

    PubMed Central

    Suwa, Masataka; Imoto, Takayuki; Kida, Akira; Yokochi, Takashi

    2016-01-01

    [Purpose] To compare the toe flexor, hand grip and knee extensor strengths of young and elderly men, and to examine the association between toe flexor strength and physical activity or inactivity levels. [Subjects and Methods] Young (n=155, 18–23 years) and elderly (n=60, 65–88 years) men participated in this study. Toe flexor, hand grip, and knee extensor strength were measured. Physical activity (time spent standing/walking per day) and inactivity (time spent sitting per day) were assessed using a self-administered questionnaire. [Results] Toe flexor, hand grip, and knee extensor strength of the elderly men were significantly lower than those of the young men. Standing/walking and sitting times of the elderly men were lower than those of the young men. Toe flexor strength correlated with hand grip and knee extensor strength in both groups. In elderly men, toe flexor strength correlated with standing/walking time. In comparison to the young men’s mean values, toe flexor strength was significantly lower than knee extensor and hand grip strength in the elderly group. [Conclusion] The results suggest that age-related reduction in toe flexor strength is greater than those of hand grip and knee extensor strengths. An early loss of toe flexor strength is likely associated with reduced physical activity in elderly men. PMID:27313353

  20. DNA binding activity of Ku during chemotherapeutic agent-induced early apoptosis.

    PubMed

    Iuchi, Katsuya; Yagura, Tatsuo

    2016-03-15

    Ku protein is a heterodimer composed of two subunits, and is capable of both sequence-independent and sequence-specific DNA binding. The former mode of DNA binding plays a crucial role in DNA repair. The biological role of Ku protein during apoptosis remains unclear. Here, we show characterization of Ku protein during apoptosis. In order to study the DNA binding properties of Ku, we used two methods for the electrophoresis mobility shift assay (EMSA). One method, RI-EMSA, which is commonly used, employed radiolabeled DNA probes. The other method, WB-EMSA, employed unlabeled DNA followed by western blot and detection with anti-Ku antiserum. In this study, Ku-DNA probe binding activity was found to dramatically decrease upon etoposide treatment, when examined by the RI-EMSA method. In addition, pre-treatment with apoptotic cell extracts inhibited Ku-DNA probe binding activity in the non-treated cell extract. The inhibitory effect of the apoptotic cell extract was reduced by DNase I treatment. WB-EMSA showed that the Ku in the apoptotic cell extract bound to fragmented endogenous DNA. Interestingly, Ku in the apoptotic cell extract purified by the Resource Q column bound 15-bp DNA in both RI-EMSA and WB-EMSA, whereas Ku in unpurified apoptotic cell extracts did not bind additional DNA. These results suggest that Ku binds cleaved chromosomal DNA and/or nucleosomes in apoptotic cells. In conclusion, Ku is intact and retains DNA binding activity in early apoptotic cells.

  1. Relationship between early autumn Arctic sea ice and East Asian wintertime transient eddy activity

    NASA Astrophysics Data System (ADS)

    Gu, Sen; Zhang, Yang; Wu, Qigang

    2015-04-01

    The Arctic sea ice is suggested with wide impacts on the winter climate over East Asia. In this study, the relationship between the early autumn Arctic sea ice and the wintertime transient eddy activity over East Asia is investigated. Our singular value decomposition (SVD) analysis between the Arctic sea ice concentration (SIC) and transient eddy kinetic energy (EKE) shows that with the decrease in SIC over the Siberia coast, Kara sea and Barents sea, the EKE around the Tibetan Plateau and the downstream regions increase significantly. This leading mode indicates that more than 60% variance of the wintertime East Asian transient eddy activity can be predicted from the SIC three month earlier. Possible dynamical processes responsible for the linkage between SIC and EKE are investigated. In the upstream of Tibetan Plateau, a branch of anomalous wave train is detected propagating southward from Ural Mountains to the North China and Tibet. In the downstream region of Tibetan Plateau, with the decrease in SIC, anomalous increase in synoptic eddy generation is found with the enhanced baroclinicity over the north slope of the Tibetan Plateau, which can result in the increase in EKE as well. Those two dynamical processes both act to enhance the transient eddy activity over East Asia.

  2. Developmental changes in brain activation and functional connectivity during response inhibition in the early childhood brain.

    PubMed

    Mehnert, Jan; Akhrif, Atae; Telkemeyer, Silke; Rossi, Sonja; Schmitz, Christoph H; Steinbrink, Jens; Wartenburger, Isabell; Obrig, Hellmuth; Neufang, Susanne

    2013-11-01

    Response inhibition is an attention function which develops relatively early during childhood. Behavioral data suggest that by the age of 3, children master the basic task requirements for the assessment of response inhibition but performance improves substantially until the age of 7. The neuronal mechanisms underlying these developmental processes, however, are not well understood. In this study, we examined brain activation patterns and behavioral performance of children aged between 4 and 6 years compared to adults by applying a go/no-go paradigm during near-infrared spectroscopy (NIRS) brain imaging. We furthermore applied task-independent functional connectivity measures to the imaging data to identify maturation of intrinsic neural functional networks. We found a significant group×condition related interaction in terms of inhibition-related reduced right fronto-parietal activation in children compared to adults. In contrast, motor-related activation did not differ between age groups. Functional connectivity analysis revealed that in the children's group, short-range coherence within frontal areas was stronger, and long-range coherence between frontal and parietal areas was weaker, compared to adults. Our findings show that in children aged from 4 to 6 years fronto-parietal brain maturation plays a crucial part in the cognitive development of response inhibition. PMID:23265620

  3. Early reduction in toe flexor strength is associated with physical activity in elderly men.

    PubMed

    Suwa, Masataka; Imoto, Takayuki; Kida, Akira; Yokochi, Takashi

    2016-05-01

    [Purpose] To compare the toe flexor, hand grip and knee extensor strengths of young and elderly men, and to examine the association between toe flexor strength and physical activity or inactivity levels. [Subjects and Methods] Young (n=155, 18-23 years) and elderly (n=60, 65-88 years) men participated in this study. Toe flexor, hand grip, and knee extensor strength were measured. Physical activity (time spent standing/walking per day) and inactivity (time spent sitting per day) were assessed using a self-administered questionnaire. [Results] Toe flexor, hand grip, and knee extensor strength of the elderly men were significantly lower than those of the young men. Standing/walking and sitting times of the elderly men were lower than those of the young men. Toe flexor strength correlated with hand grip and knee extensor strength in both groups. In elderly men, toe flexor strength correlated with standing/walking time. In comparison to the young men's mean values, toe flexor strength was significantly lower than knee extensor and hand grip strength in the elderly group. [Conclusion] The results suggest that age-related reduction in toe flexor strength is greater than those of hand grip and knee extensor strengths. An early loss of toe flexor strength is likely associated with reduced physical activity in elderly men. PMID:27313353

  4. Immunodetection of histone epitopes correlates with early stages of apoptosis in activated human peripheral T lymphocytes.

    PubMed Central

    Zunino, S. J.; Singh, M. K.; Bass, J.; Picker, L. J.

    1996-01-01

    By coupling intracellular staining with terminal deoxynucleotidyl transferase (TdT)-mediated labeling of internucleosomal DNA strand breaks in a flow cytometric assay, we observed a strong correlation between apoptosis-associated DNA strand breaks and immunoreactivity with the monoclonal antibody (MAb) B-F6 in activated human peripheral blood T lymphocytes (PBTs). Although MAb B-F6 has been reported to be specific for the cytokine interleukin-6, Western blot analysis of activated PBT lysates revealed that the predominant protein band detected by this MAb was 17 kd (p17), distinct from the 23-kd core protein and 26- to 30-kd mature glycosylated forms of interleukin-6. Immunoaffinity isolation and amino-terminal amino acid sequence analysis of p17 revealed identity with the histone H2B, a finding confirmed by Western blot analysis of purified histones and by similar staining of activated PBTs with an unrelated anti-histone MAb. Neither histone staining nor DNA strand breakage was observed in freshly isolated PBTs; however, after T cell activation, histone immunoreactivity appeared to precede the appearance of DNA strand breaks, with both increasing to a maximal level by day 3 after activation. Two-parameter confocal immunofluorescence microscopy of histone and DNA staining confirmed a lack of histone immunoreactivity in viable cells and demonstrated co-localization of histone epitopes with abnormally clumped chromatin in apoptotic cells. These data indicate that alteration of histone epitope accessibility is a marker of early apoptosis and suggest that multiparameter flow cytometric analysis of intracellular epitopes may be a powerful tool in the elucidation of intracellular mechanisms of apoptosis. Images Figure 4 Figure 5 Figure 6 Figure 8 PMID:8702003

  5. Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice.

    PubMed

    Flores-Montoya, Mayra Gisel; Sobin, Christina

    2015-07-01

    Research has suggested that chronic low-level lead exposure diminishes neurocognitive function in children. Tests that are sensitive to behavioral effects at lowest levels of lead exposure are needed for the development of animal models. In this study we investigated the effects of chronic low-level lead exposure on exploratory activity (unbaited nose poke task), exploratory ambulation (open field task) and motor coordination (Rotarod task) in pre-adolescent mice. C57BL/6J pups were exposed to 0 ppm (controls), 30 ppm (low-dose) or 230 ppm (high-dose) lead acetate via dams' drinking water administered from birth to postnatal day 28, to achieve a range of blood lead levels (BLLs) from not detectable to 14.84 µg dl(-1) ). At postnatal day 28, mice completed behavioral testing and were killed (n = 61). BLLs were determined by inductively coupled plasma mass spectrometry. The effects of lead exposure on behavior were tested using generalized linear mixed model analyses with BLL, sex and the interaction as fixed effects, and litter as the random effect. BLL predicted decreased exploratory activity and no threshold of effect was apparent. As BLL increased, nose pokes decreased. The C57BL/6J mouse is a useful model for examining effects of early chronic low-level lead exposure on behavior. In the C57BL/6J mouse, the unbaited nose poke task is sensitive to the effects of early chronic low-level lead exposure. This is the first animal study to show behavioral effects in pre-adolescent lead-exposed mice with BLL below 5 µg dl(-1).

  6. Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice.

    PubMed

    Flores-Montoya, Mayra Gisel; Sobin, Christina

    2015-07-01

    Research has suggested that chronic low-level lead exposure diminishes neurocognitive function in children. Tests that are sensitive to behavioral effects at lowest levels of lead exposure are needed for the development of animal models. In this study we investigated the effects of chronic low-level lead exposure on exploratory activity (unbaited nose poke task), exploratory ambulation (open field task) and motor coordination (Rotarod task) in pre-adolescent mice. C57BL/6J pups were exposed to 0 ppm (controls), 30 ppm (low-dose) or 230 ppm (high-dose) lead acetate via dams' drinking water administered from birth to postnatal day 28, to achieve a range of blood lead levels (BLLs) from not detectable to 14.84 µg dl(-1) ). At postnatal day 28, mice completed behavioral testing and were killed (n = 61). BLLs were determined by inductively coupled plasma mass spectrometry. The effects of lead exposure on behavior were tested using generalized linear mixed model analyses with BLL, sex and the interaction as fixed effects, and litter as the random effect. BLL predicted decreased exploratory activity and no threshold of effect was apparent. As BLL increased, nose pokes decreased. The C57BL/6J mouse is a useful model for examining effects of early chronic low-level lead exposure on behavior. In the C57BL/6J mouse, the unbaited nose poke task is sensitive to the effects of early chronic low-level lead exposure. This is the first animal study to show behavioral effects in pre-adolescent lead-exposed mice with BLL below 5 µg dl(-1). PMID:25219894

  7. Mouse early extra-embryonic lineages activate compensatory endocytosis in response to poor maternal nutrition.

    PubMed

    Sun, Congshan; Velazquez, Miguel A; Marfy-Smith, Stephanie; Sheth, Bhavwanti; Cox, Andy; Johnston, David A; Smyth, Neil; Fleming, Tom P

    2014-03-01

    Mammalian extra-embryonic lineages perform the crucial role of nutrient provision during gestation to support embryonic and fetal growth. These lineages derive from outer trophectoderm (TE) and internal primitive endoderm (PE) in the blastocyst and subsequently give rise to chorio-allantoic and visceral yolk sac placentae, respectively. We have shown maternal low protein diet exclusively during mouse preimplantation development (Emb-LPD) is sufficient to cause a compensatory increase in fetal and perinatal growth that correlates positively with increased adult-onset cardiovascular, metabolic and behavioural disease. Here, to investigate early mechanisms of compensatory nutrient provision, we assessed the influence of maternal Emb-LPD on endocytosis within extra-embryonic lineages using quantitative imaging and expression of markers and proteins involved. Blastocysts collected from Emb-LPD mothers within standard culture medium displayed enhanced TE endocytosis compared with embryos from control mothers with respect to the number and collective volume per cell of vesicles with endocytosed ligand and fluid and lysosomes, plus protein expression of megalin (Lrp2) LDL-family receptor. Endocytosis was also stimulated using similar criteria in the outer PE-like lineage of embryoid bodies formed from embryonic stem cell lines generated from Emb-LPD blastocysts. Using an in vitro model replicating the depleted amino acid (AA) composition found within the Emb-LPD uterine luminal fluid, we show TE endocytosis response is activated through reduced branched-chain AAs (leucine, isoleucine, valine). Moreover, activation appears mediated through RhoA GTPase signalling. Our data indicate early embryos regulate and stabilise endocytosis as a mechanism to compensate for poor maternal nutrient provision.

  8. Early warning of active fire hotspots through NASA FIRMS fire information system

    NASA Astrophysics Data System (ADS)

    Ilavajhala, S.; Davies, D.; Schmaltz, J. E.; Murphy, K. J.

    2014-12-01

    Forest fires and wildfires can threaten ecosystems, wildlife, property, and often, large swaths of populations. Early warning of active fire hotspots plays a crucial role in planning, managing, and mitigating the damaging effects of wildfires. The NASA Fire Information for Resource Management System (FIRMS) has been providing active fire location information to users in easy-to-use formats for the better part of last decade, with a view to improving the alerting mechanisms and response times to fight forest and wildfires. FIRMS utilizes fires flagged as hotspots by the MODIS instrument flying aboard the Aqua and Terra satellites and sends early warning of detected hotspots via email in near real-time or as daily and weekly summaries. The email alerts can also be customized to send alerts for a particular region of interest, a country, or a specific protected area or park. In addition, a web mapping component, named "Web Fire Mapper" helps query and visualize hotspots. A newer version of Web Fire Mapper is being developed to enhance the existing visualization and alerting capabilities. Plans include supporting near real-time imagery from Aqua and Terra satellites to provide a more helpful context while viewing fires. Plans are also underway to upgrade the email alerts system to provide mobile-formatted messages and short text messages (SMS). The newer version of FIRMS will also allow users to obtain geo-located image snapshots, which can be imported into local GIS software by stakeholders to help further analyses. This talk will discuss the FIRMS system, its enhancements and its role in helping map, alert, and monitor fire hotspots by providing quick data visualization, querying, and download capabilities.

  9. Early Holocene dune activity linked with final destruction of Glacial Lake Minong, eastern Upper Michigan, USA

    NASA Astrophysics Data System (ADS)

    Loope, Henry M.; Loope, Walter L.; Goble, Ronald J.; Fisher, Timothy G.; Jol, Harry M.; Seong, J. C.

    2010-07-01

    The early Holocene final drainage of glacial Lake Minong is documented by 21 OSL ages on quartz sand from parabolic dunes and littoral terraces and one radiocarbon age from a lake sediment core adjacent to mapped paleoshorelines in interior eastern Upper Michigan. We employ a simple model wherein lake-level decline exposes unvegetated littoral sediment to deflation, resulting in dune building. Dunes formed subsequent to lake-level decline prior to stabilization by vegetation and provide minimum ages for lake-level decline. Optical ages range from 10.3 to 7.7 ka; 15 ages on dunes adjacent to the lowest Lake Minong shoreline suggest final water-level decline ˜ 9.1 ka. The clustering of optical ages from vertically separated dunes on both sides of the Nadoway-Gros Cap Barrier around 8.8 ka and a basal radiocarbon date behind the barrier (8120 ± 40 14C yr BP [9.1 cal ka BP]) support the hypothesis that the barrier was breached and the final lake-level drop to the Houghton Low occurred coincident with (1) high meltwater flux into the Superior basin and (2) an abrupt, negative shift in oxygen isotope values in Lake Huron.

  10. Patterns of Organized Activity Participation in Urban, Early Adolescents: Associations with Academic Achievement, Problem Behaviors, and Perceived Adult Support

    ERIC Educational Resources Information Center

    Metzger, Aaron; Crean, Hugh F.; Forbes-Jones, Emma L.

    2009-01-01

    This study examines patterns of organized activity and their concurrent association with academic achievement, problem behavior, and perceived adult support in a sample of urban, early adolescent, middle school students (mean age = 13.01; N = 2,495). Cluster analyses yielded six activity profiles: an uninvolved group (n = 775, 31.1%), a multiply…

  11. Early active rehabilitation after surgery for lumbar disc herniation: a prospective, randomized study of psychometric assessment in 50 patients.

    PubMed

    Kjellby-Wendt, G; Styf, J; Carlsson, S G

    2001-10-01

    In a randomized study, using psychometric assessment, we evaluated two training programs before and after surgical treatment of lumbar disc herniation. 26 patients were treated according to an early active training program (treatment group). 24 patients followed a traditional less active training program (control group). Before surgery, the patients filled in the following questionnaires 3 and 12 months after surgery: Multidimensional Pain Inventory (MPI), State and Trait Anxiety Inventory, and Beck Depression Inventory. Pain was assessed by the patient's pain drawing and a visual analog scale. Both groups improved as regards pain severity and state of anxiety. The MPI parameter, pain interference, improved more in the early active treatment group than in the control group. This suggests that the early active training program has a positive effect on the way patients cope with pain in their daily lives. PMID:11728081

  12. Hepatocellular hypertrophy and cell proliferation in Sprague-Dawley rats following dietary exposure to ammonium perfluorooctanoate occurs through increased activation of the xenosensor nuclear receptors PPARα and CAR/PXR.

    PubMed

    Elcombe, Clifford R; Elcombe, Barbara M; Foster, John R; Farrar, David G; Jung, Reinhard; Chang, Shu-Ching; Kennedy, Gerald L; Butenhoff, John L

    2010-10-01

    Ammonium perfluorooctanoate (APFO), a processing aid used in the production of fluoropolymers, produces hepatomegaly and hepatocellular hypertrophy in rodents. In mice, APFO-induced hepatomegaly is associated with increased activation of the xenosensor nuclear receptors, PPARα and CAR/PXR. Although non-genotoxic, chronic dietary treatment of Sprague-Dawley (S-D) rats with APFO produced an increase in benign tumours of the liver, acinar pancreas, and testicular Leydig cells. Most of the criteria for establishing a PPARα-mediated mode of action for the observed hepatocellular tumours have been previously established with the exception of the demonstration of increased hepatocellular proliferation. The present study evaluates the potential roles for APFO-induced activation of PPARα and CAR/PXR with respect to liver tumour production in the S-D rat and when compared to the specific PPARα agonist, 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid (Wy 14,643). Male S-D rats were fed APFO (300 ppm in diet) or Wy 14,643 (50 ppm in diet) for either 1, 7, or 28 days. Effects of treatment with APFO included: decreased body weight; hepatomegaly, hepatocellular hypertrophy, hepatocellular hyperplasia (microscopically and by BrdU labelling index), and hepatocellular glycogen loss; increased activation of PPARα (peroxisomal β-oxidation and microsomal CYP4A1 protein); decreased plasma triglycerides, cholesterol, and glucose; increased activation of CAR (CYP2B1/2 protein) and CAR/PXR (CYP3A1 protein). Responses to treatment with Wy 14,643 were consistent with increased activation of PPARα, specifically: increased CYP4A1 and peroxisomal β-oxidation; increased hepatocellular hypertrophy and cell proliferation; decreased apoptosis; and hypolipidaemia. With the exception of decreased apoptosis, the effects observed with Wy 14,643 were noted with APFO, and APFO was less potent. These data clearly demonstrate an early hepatocellular proliferative response to APFO

  13. Raised bogs, a Climate Shift, Cultural Change, and Reduced Solar Activity in the Early First Millennium BC

    NASA Astrophysics Data System (ADS)

    van Geel, B.

    2006-12-01

    Matching of a high resolution sequence of uncalibrated 14C datings with the dendro-calibration curve not only offers improved dating precision, but can also reveal relationships between atmospheric 14C variations and short-term climatic fluctuations caused by variations in solar output. Holocene shifts to cool and wet climate types in the temperate zones often correspond to phases of sharply increasing values of atmospheric radiocarbon, pointing to a link between changing solar activity and climate change. In northwest Europe at ca. 850 BC a sharp climatic shift to cooler, wetter conditions occurred. The shift is reflected in the species composition and decomposition of raised bog deposits and is chronologically linked to cultural changes and migrations at the Bronze Age/Iron Age transition. The temporary sharp rise of the atmospheric 14C content around 800 BC was caused by a sudden decline of solar activity. The solar wind declined, permitting more cosmic rays to penetrate into the atmosphere, and therefore the production of the cosmogenic isotope 14C increased. The climate shift was also recorded in Central and Eastern Europe, with rapid and total flooding of the Upper Volga region and a highstand of the Caspian Sea. In the Mississippi River basin, flooding frequencies greatly increased and there was an abrupt gap in the cultural transition from `Late Archaic' to `Early Woodland'. Paleoclimatological teleconnections point to a considerable role of solar UV in climate forcing. In the Central African rain forest belt and western India there was also a strong climate shift around 850 cal BC, but it was a shift to dryness (weakening of the summer monsoon). A possible palaeoclimatological explanation for the dry-wet transition in the temperate zones, and the contemporaneous wet-dry transition in the tropics (climatic teleconnections) will be given.

  14. Immediate early gene expression reveals interactions between social and nicotine rewards on brain activity in adolescent male rats.

    PubMed

    Bastle, Ryan M; Peartree, Natalie A; Goenaga, Julianna; Hatch, Kayla N; Henricks, Angela; Scott, Samantha; Hood, Lauren E; Neisewander, Janet L

    2016-10-15

    Smoking initiation predominantly occurs during adolescence, often in the presence of peers. Therefore, understanding the neural mechanisms underlying the rewarding effects of nicotine and social stimuli is vital. Using the conditioned place preference (CPP) procedure, we measured immediate early gene (IEG) expression in animals following exposure either to a reward-conditioned environment or to the unconditioned stimuli (US). Adolescent, male rats were assigned to the following CPP US conditions: (1) Saline+Isolated, (2) Nicotine+Isolated, (3) Saline+Social, or (4) Nicotine+Social. For Experiment 1, brain tissue was collected 90min following the CPP expression test and processed for Fos immunohistochemistry. We found that rats conditioned with nicotine with or without a social partner exhibited CPP; however, we found no group differences in Fos expression in any brain region analyzed, with the exception of the nucleus accumbens core that exhibited a social-induced attenuation in Fos expression. For Experiment 2, brain tissue was collected 90min following US exposure during the last conditioning session. We found social reward-induced increases in IEG expression in striatal and amydalar subregions. In contrast, nicotine reduced IEG expression in prefrontal and striatal subregions. Reward interactions were also found in the dorsolateral striatum, basolateral amygdala, and ventral tegmental area where nicotine alone attenuated IEG expression and social reward reversed this effect. These results suggest that in general social rewards enhance, whereas nicotine attenuates, activation of mesocorticolimbic regions; however, the rewards given together interact to enhance activation in some regions. The findings contribute to knowledge of how a social environment influences nicotine effects.

  15. Transcriptionally active immediate-early protein of pseudorabies virus binds to specific sites on class II gene promoters.

    PubMed Central

    Cromlish, W A; Abmayr, S M; Workman, J L; Horikoshi, M; Roeder, R G

    1989-01-01

    In the presence of partially purified pseudorabies virus immediate-early protein, multiple sites of DNase I protection were observed on the adenovirus major late and human hsp 70 promoters. Southwestern (DNA-protein blot) analysis demonstrated that the immediate-early protein bound directly to the sequences contained in these sites. These sequences share only limited homology, differ in their affinities for the immediate-early protein, and are located at different positions on these two promoters. In addition, the site-specific binding of a temperature-sensitive immediate-early protein was eliminated by the same heat treatment which eliminates its transcriptional activating function, whereas the binding of the wild-type protein was unaffected by heat treatment. Thus, site-specific binding requires a functionally active immediate-early protein. Furthermore, immediate-early-protein-dependent in vitro transcription from the major late promoter was preferentially inhibited by oligonucleotides which are homologous to the high-affinity binding sites on the major late or hsp 70 promoters. These observations suggest that transcriptional stimulation by the immediate-early protein involves binding to cis-acting elements. Images PMID:2539489

  16. Activation of endogenous angiotensin converting enzyme 2 prevents early injuries induced by hyperglycemia in rat retina

    PubMed Central

    Foureaux, G.; Nogueira, B. S.; Coutinho, D. C. O.; Raizada, M. K.; Nogueira, J. C.; Ferreira, A. J.

    2015-01-01

    Diabetic retinopathy (DR) is a serious complication of diabetes mellitus that may result in blindness. We evaluated the effects of activation of endogenous angiotensin converting enzyme (ACE) 2 on the early stages of DR. Rats were administered an intravenous injection of streptozotocin to induce hyperglycemia. The ACE2 activator 1-[[2-(dimethylamino) ethyl] amino]-4-(hydroxymethyl)-7-[[(4-methylphenyl) sulfonyl] oxy]-9H-xanthone 9 (XNT) was administered by daily gavage. The death of retinal ganglion cells (RGC) was evaluated in histological sections, and retinal ACE2, caspase-3, and vascular endothelial growth factor (VEGF) expressions were analyzed by immunohistochemistry. XNT treatment increased ACE2 expression in retinas of hyperglycemic (HG) rats (control: 13.81±2.71 area%; HG: 14.29±4.30 area%; HG+XNT: 26.87±1.86 area%; P<0.05). Importantly, ACE2 activation significantly increased the RCG number in comparison with HG animals (control: 553.5±14.29; HG: 530.8±10.3 cells; HG+XNT: 575.3±16.5 cells; P<0.05). This effect was accompanied by a reduction in the expression of caspase-3 in RGC of the HG+XNT group when compared with untreated HG rats (control: 18.74±1.59; HG: 38.39±3.39 area%; HG+XNT: 27.83±2.80 area%; P<0.05). Treatment with XNT did not alter the VEGF expression in HG animals (P>0.05). Altogether, these findings indicate that activation of ACE2 reduced the death of retinal ganglion cells by apoptosis in HG rats. PMID:26421871

  17. Activation of calpains mediates early lung neutrophilic inflammation in ventilator-induced lung injury

    PubMed Central

    Liu, Dejie; Yan, Zhibo; Minshall, Richard D.; Schwartz, David E.; Chen, Yuguo

    2012-01-01

    Lung inflammatory responses in the absence of infection are considered to be one of primary mechanisms of ventilator-induced lung injury. Here, we determined the role of calpain in the pathogenesis of lung inflammation attributable to mechanical ventilation. Male C57BL/6J mice were subjected to high (28 ml/kg) tidal volume ventilation for 2 h in the absence and presence of calpain inhibitor I (10 mg/kg). To address the isoform-specific functions of calpain 1 and calpain 2 during mechanical ventilation, we utilized a liposome-based delivery system to introduce small interfering RNAs targeting each isoform in pulmonary vasculature in vivo. Mechanical ventilation with high tidal volume induced rapid (within minutes) and persistent calpain activation and lung inflammation as evidenced by neutrophil recruitment, production of TNF-α and IL-6, pulmonary vascular hyperpermeability, and lung edema formation. Pharmaceutical calpain inhibition significantly attenuated these inflammatory responses caused by lung hyperinflation. Depletion of calpain 1 or calpain 2 had a protective effect against ventilator-induced lung inflammatory responses. Inhibition of calpain activity by means of siRNA silencing or pharmacological inhibition also reduced endothelial nitric oxide (NO) synthase (NOS-3)-mediated NO production and subsequent ICAM-1 phosphorylation following high tidal volume ventilation. These results suggest that calpain activation mediates early lung inflammation during ventilator-induced lung injury via NOS-3/NO-dependent ICAM-1 phosphorylation and neutrophil recruitment. Inhibition of calpain activation may therefore provide a novel and promising strategy for the prevention and treatment of ventilator-induced lung injury. PMID:22140070

  18. Development of an early-tier laboratory bioassay for assessing the impact of orally-active insecticidal compounds on larvae of Coccinella septempunctata (Coleoptera: Coccinellidae).

    PubMed

    Alvarez-Alfageme, Fernando; Pálinkás, Zoltan; Bigler, Franz; Romeis, Jörg

    2012-12-01

    Early-tier studies are the initial step in the environmental risk assessment of genetically engineered plants on nontarget arthropods. They are conducted in the laboratory where surrogate species are exposed to higher concentrations of the arthropod-active compound than those expected to occur in the field. Thus, early-tier tests provide robust data and allow to make general conclusions about the susceptibility of the surrogate to the test substance. We have developed an early-tier test for assessing the toxicity of orally-active insecticidal compounds to larvae of the ladybird beetle Coccinella septempunctata L. (Coleoptera: Coccinellidae). Using potassium arsenate and the protease inhibitor E-64 as model compounds, we validated the bioassay set-up for C. septempunctata. Sucrose solution containing the test compound was offered to larvae for 24 h on the first day of each of its four larval instars. Subsequently, larvae were fed ad libitum with Ephestia kuehniella (Zeller) (Lepidoptera: Pyralidae) eggs. Both compounds negatively affected C. septempunctata larval survival and development, and adult weight, indicating that the bioassay setup was able to detect dietary effects of insecticidal substances on the ladybird. Power analyses revealed that sample sizes of 20 or 45 per treatment are sufficient to detect 50 or 20% differences between the control and treatment groups, respectively, for the various measurement endpoints. PMID:23321119

  19. Activation of oxidative stress-responsive signaling pathways in early splenotoxic response of aniline

    SciTech Connect

    Wang Jianling; Wang Gangduo; Ansari, G.A.S.; Khan, M. Firoze

    2008-07-15

    Aniline exposure causes toxicity to the spleen, which leads to a variety of sarcomas, and fibrosis appears to be an important preneoplastic lesion. However, early molecular mechanisms in aniline-induced toxicity to the spleen are not known. Previously, we have shown that aniline exposure results in iron overload and induction of oxidative stress in the spleen, which can cause transcriptional upregulation of fibrogenic/inflammatory cytokines via activation of oxidative stress (OS)-responsive signaling pathways. To test this mechanism, male SD rats were treated with aniline (1mmol/kg/day via gavage) for 7days, an experimental condition that precedes the appearance of fibrosis. Significant increases in both NF-{kappa}B and AP-1 binding activity was observed in the nuclear extracts of splenocytes from aniline-treated rats as determined by ELISAs, and supported by Western blot data showing increases in p-I{kappa}B{alpha}, p-p65 and p-c-Jun. To understand the upstream signaling events which could account for the activation of NF-{kappa}B and AP-1, phosphorylation patterns of I{kappa}B kinases (IKK{alpha} and IKK{beta}) and mitogen-activated protein kinases (MAPKs) were pursued. Our data showed remarkable increases in both p-IKK{alpha} and p-IKK{beta} in the splenocytes from aniline-treated rats, suggesting their role in the phosphorylation of both I{kappa}B{alpha} and p65 subunits. Furthermore, aniline exposure led to activation of all three classes of MAPKs, as evident from increased phosphorylation of extracellular-signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK1/2) and p38 MAPKs, which could potentially contribute to the observed activation of both AP-1 and NF-{kappa}B. Activation of upstream signaling molecules was also associated with simultaneous increases in gene transcription of cytokines IL-1, IL-6 and TNF-{alpha}. The observed sequence of events following aniline exposure could initiate a fibrogenic and/or tumorigenic response in the spleen.

  20. Naturally Occurring Radioactive Materials (NORM)

    SciTech Connect

    Gray, P.

    1997-02-01

    This paper discusses the broad problems presented by Naturally Occuring Radioactive Materials (NORM). Technologically Enhanced naturally occuring radioactive material includes any radionuclides whose physical, chemical, radiological properties or radionuclide concentration have been altered from their natural state. With regard to NORM in particular, radioactive contamination is radioactive material in an undesired location. This is a concern in a range of industries: petroleum; uranium mining; phosphorus and phosphates; fertilizers; fossil fuels; forestry products; water treatment; metal mining and processing; geothermal energy. The author discusses in more detail the problem in the petroleum industry, including the isotopes of concern, the hazards they present, the contamination which they cause, ways to dispose of contaminated materials, and regulatory issues. He points out there are three key programs to reduce legal exposure and problems due to these contaminants: waste minimization; NORM assesment (surveys); NORM compliance (training).

  1. Foliicolous microfungi occurring on Encephalartos.

    PubMed

    Crous, P W; Wood, A R; Okada, G; Groenewald, J Z

    2008-12-01

    Species of Encephalartos, commonly known as bread trees, bread palms or cycads are native to Africa; the genus encompasses more than 60 species and represents an important component of the indigenous African flora. Recently, a leaf blight disease was noted on several E. altensteinii plants growing at the foot of Table Mountain in the Kirstenbosch Botanical Gardens of South Africa. Preliminary isolations from dead and dying leaves of E. alten-steinii, E. lebomboensis and E. princeps, collected from South Africa, revealed the presence of several novel microfungi on this host. Novelties include Phaeomoniella capensis, Saccharata kirstenboschensis, Teratosphaeria altensteinii and T. encephalarti. New host records of species previously only known to occur on Proteaceae include Cladophialophora proteae and Catenulostroma microsporum, as well as a hyperparasite, Dactylaria leptosphaeriicola, occurring on ascomata of T. encephalarti. PMID:20396583

  2. Early cerebral volume reductions and their associations with reduced lupus disease activity in patients with newly-diagnosed systemic lupus erythematosus.

    PubMed

    Mak, Anselm; Ho, Roger Chun-Man; Tng, Han-Ying; Koh, Hui Li; Chong, Joanna Su Xian; Zhou, Juan

    2016-03-01

    We examined if cerebral volume reduction occurs very early during the course of systemic lupus erythematosus (SLE), and observed prospectively whether gray (GMV) and white matter volumes (WMV) of the brain would improve with lowered SLE disease activity. T1-weighted MRI brain images were obtained from 14 healthy controls (HC) and 14 newly-diagnosed SLE patients within 5 months of diagnosis (S1) and after achieving low disease activity (S2). Whole brain voxel-based morphometry was used to detect differences in the GMV and WMV between SLE patients and HC and those between SLE patients at S1 and S2. SLE patients were found to have lower GMV than HC in the middle cingulate cortex, middle frontal gyrus and right supplementary motor area, and lower WMV in the superior longitudinal fasciculus, cingulum cingulate gyrus and inferior fronto-occipital fasciculus at both S1 and S2. Whole-brain voxel-wise analysis revealed increased GMV chiefly in the prefrontal regions at S2 compared to S1 in SLE patients. The GMV increase in the left superior frontal gyrus was significantly associated with lowered SLE disease activity. In conclusion, GMV and WMV reduced very early in SLE patients. Reduction of SLE disease activity was accompanied by region-specific GMV improvement in the prefrontal regions.

  3. Early cerebral volume reductions and their associations with reduced lupus disease activity in patients with newly-diagnosed systemic lupus erythematosus

    PubMed Central

    Mak, Anselm; Ho, Roger Chun-Man; Tng, Han-Ying; Koh, Hui Li; Chong, Joanna Su Xian; Zhou, Juan

    2016-01-01

    We examined if cerebral volume reduction occurs very early during the course of systemic lupus erythematosus (SLE), and observed prospectively whether gray (GMV) and white matter volumes (WMV) of the brain would improve with lowered SLE disease activity. T1-weighted MRI brain images were obtained from 14 healthy controls (HC) and 14 newly-diagnosed SLE patients within 5 months of diagnosis (S1) and after achieving low disease activity (S2). Whole brain voxel-based morphometry was used to detect differences in the GMV and WMV between SLE patients and HC and those between SLE patients at S1 and S2. SLE patients were found to have lower GMV than HC in the middle cingulate cortex, middle frontal gyrus and right supplementary motor area, and lower WMV in the superior longitudinal fasciculus, cingulum cingulate gyrus and inferior fronto-occipital fasciculus at both S1 and S2. Whole-brain voxel-wise analysis revealed increased GMV chiefly in the prefrontal regions at S2 compared to S1 in SLE patients. The GMV increase in the left superior frontal gyrus was significantly associated with lowered SLE disease activity. In conclusion, GMV and WMV reduced very early in SLE patients. Reduction of SLE disease activity was accompanied by region-specific GMV improvement in the prefrontal regions. PMID:26928214

  4. IgG-Mediated Immune Suppression to Erythrocytes by Polyclonal Antibodies Can Occur in the Absence of Activating or Inhibitory Fcγ Receptors in a Full Mouse Model.

    PubMed

    Bernardo, Lidice; Yu, Honghui; Amash, Alaa; Zimring, James C; Lazarus, Alan H

    2015-09-01

    Polyclonal anti-D has been used to prevent RhD-negative mothers from becoming immunized against RhD positive fetal erythrocytes, and this mechanism has been referred as Ab or IgG-mediated immune suppression (AMIS). Although anti-D has been highly successful, the inhibitory mechanisms remain poorly understood. Two major theories behind AMIS involve the binding of IgG to activating or inhibitory FcγR, which can induce either erythrocyte clearance or immune inhibition, respectively. In this work, we explored the absolute role of activating and inhibitory FcγR in the AMIS mechanism using the HOD mouse model of RBC immunization. HOD mice contain a RBC-specific recombinant protein composed of hen egg lysozyme (HEL), OVA and human transmembrane Duffy Ag, and erythrocytes from HOD mice can stimulate an immune response to HEL. To assess the contribution of activating and inhibitory FcγR to AMIS, C57BL/6 versus FcRγ-chain(-/-) or FcγRIIB(-/-) mice were used as recipients of HOD-RBC alone or together with anti-HEL Abs (i.e., AMIS) and the resulting immune response to HEL evaluated. We show that anti-HEL polyclonal Abs induce the same degree of AMIS effect in mice lacking these IgG binding receptors as compared with wild-type mice. In agreement with this, F(ab')2 fragments of the AMIS Ab also significantly reduced the Ab response to the HOD cells. In conclusion, successful inhibition of in vivo Ab responses to HOD-RBC by polyclonal IgG can occur independently of activating or inhibitory FcγR involvement. These results may have implications for the understanding of RhD prophylaxis.

  5. IgG-Mediated Immune Suppression to Erythrocytes by Polyclonal Antibodies Can Occur in the Absence of Activating or Inhibitory Fcγ Receptors in a Full Mouse Model.

    PubMed

    Bernardo, Lidice; Yu, Honghui; Amash, Alaa; Zimring, James C; Lazarus, Alan H

    2015-09-01

    Polyclonal anti-D has been used to prevent RhD-negative mothers from becoming immunized against RhD positive fetal erythrocytes, and this mechanism has been referred as Ab or IgG-mediated immune suppression (AMIS). Although anti-D has been highly successful, the inhibitory mechanisms remain poorly understood. Two major theories behind AMIS involve the binding of IgG to activating or inhibitory FcγR, which can induce either erythrocyte clearance or immune inhibition, respectively. In this work, we explored the absolute role of activating and inhibitory FcγR in the AMIS mechanism using the HOD mouse model of RBC immunization. HOD mice contain a RBC-specific recombinant protein composed of hen egg lysozyme (HEL), OVA and human transmembrane Duffy Ag, and erythrocytes from HOD mice can stimulate an immune response to HEL. To assess the contribution of activating and inhibitory FcγR to AMIS, C57BL/6 versus FcRγ-chain(-/-) or FcγRIIB(-/-) mice were used as recipients of HOD-RBC alone or together with anti-HEL Abs (i.e., AMIS) and the resulting immune response to HEL evaluated. We show that anti-HEL polyclonal Abs induce the same degree of AMIS effect in mice lacking these IgG binding receptors as compared with wild-type mice. In agreement with this, F(ab')2 fragments of the AMIS Ab also significantly reduced the Ab response to the HOD cells. In conclusion, successful inhibition of in vivo Ab responses to HOD-RBC by polyclonal IgG can occur independently of activating or inhibitory FcγR involvement. These results may have implications for the understanding of RhD prophylaxis. PMID:26188060

  6. The Dynamic Behavior of the Early Dental Caries Lesion in Caries-active Adults and Implications

    PubMed Central

    Brown, J P; Amaechi, B T; Bader, J D; Shugars, D; Vollmer, W M; Chen, C; Gilbert, G H; Esterberg, E J

    2015-01-01

    Objective To describe the full range of behavior of the visible, non-cavitated, early caries lesion in caries-active adults with substantial fluoride exposure, and to consider implications. Methods The data were from the Xylitol for Adult Caries Trial (X-ACT), collected annually for 33 months using condensed ICDAS caries threshold criteria. Individual tooth surfaces having a non-cavitated caries lesion were included and the Patterns of transition to each subsequent annual clinical examination to sound, non-cavitated or cavitated, filled or crowned were determined. The resulting sets of Patterns for an individual tooth surface, looking forward from its first appearance as a non-cavitated lesion, were combined into one of four behavior Profiles classified as Reversing, Stable, Oscillating or continuously Progressing, or were excluded if not part of the caries continuum. The distributions of Profile types were assessed using the Rao-Scott Chi square test, which adjusts for clustering of tooth surfaces within teeth. Results Inter-and intra-examiner Kappa scores demonstrated acceptable calibration at baseline and annually. 8084 tooth surfaces from 543 subjects were included. The distribution of Profile types differed significantly between coronal and root surfaces. Overall two-thirds of all coronal non-cavitated lesions were first seen at baseline, half Reversed, over a fifth were Stable, 15% Oscillated and only 8.3% progressed to cavitation, filled or crowned in 33 months or less. (6.3% consistently Progressed plus 2.0% inconsistently, a subset of Oscillating, which oscillated before progressing to cavitation). Approximal, smooth and occlusal coronal surfaces each were significantly different in their individual distributions of Profile types. Xylitol showed no significant and consistent effect on this distribution by tooth surface type. This was in keeping with the X-ACT Trial’s lack of effect of xylitol at the non-cavitated plus cavitated lesion thresholds combined

  7. Inhibition of Btk with CC-292 provides early pharmacodynamic assessment of activity in mice and humans.

    PubMed

    Evans, Erica K; Tester, Richland; Aslanian, Sharon; Karp, Russell; Sheets, Michael; Labenski, Matthew T; Witowski, Steven R; Lounsbury, Heather; Chaturvedi, Prasoon; Mazdiyasni, Hormoz; Zhu, Zhendong; Nacht, Mariana; Freed, Martin I; Petter, Russell C; Dubrovskiy, Alex; Singh, Juswinder; Westlin, William F

    2013-08-01

    Targeted therapies that suppress B cell receptor (BCR) signaling have emerged as promising agents in autoimmune disease and B cell malignancies. Bruton's tyrosine kinase (Btk) plays a crucial role in B cell development and activation through the BCR signaling pathway and represents a new target for diseases characterized by inappropriate B cell activity. N-(3-(5-fluoro-2-(4-(2-methoxyethoxy)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide (CC-292) is a highly selective, covalent Btk inhibitor and a sensitive and quantitative assay that measures CC-292-Btk engagement has been developed. This translational pharmacodynamic assay has accompanied CC-292 through each step of drug discovery and development. These studies demonstrate the quantity of Btk bound by CC-292 correlates with the efficacy of CC-292 in vitro and in the collagen-induced arthritis model of autoimmune disease. Recently, CC-292 has entered human clinical trials with a trial design that has provided rapid insight into safety, pharmacokinetics, and pharmacodynamics. This first-in-human healthy volunteer trial has demonstrated that a single oral dose of 2 mg/kg CC-292 consistently engaged all circulating Btk protein and provides the basis for rational dose selection in future clinical trials. This targeted covalent drug design approach has enabled the discovery and early clinical development of CC-292 and has provided support for Btk as a valuable drug target for B-cell mediated disorders.

  8. Modeling spontaneous activity across an excitable epithelium: Support for a coordination scenario of early neural evolution

    PubMed Central

    de Wiljes, Oltman O.; van Elburg, Ronald A. J.; Biehl, Michael; Keijzer, Fred A.

    2015-01-01

    Internal coordination models hold that early nervous systems evolved in the first place to coordinate internal activity at a multicellular level, most notably the use of multicellular contractility as an effector for motility. A recent example of such a model, the skin brain thesis, suggests that excitable epithelia using chemical signaling are a potential candidate as a nervous system precursor. We developed a computational model and a measure for whole body coordination to investigate the coordinative properties of such excitable epithelia. Using this measure we show that excitable epithelia can spontaneously exhibit body-scale patterns of activation. Relevant factors determining the extent of patterning are the noise level for exocytosis, relative body dimensions, and body size. In smaller bodies whole-body coordination emerges from cellular excitability and bidirectional excitatory transmission alone. Our results show that basic internal coordination as proposed by the skin brain thesis could have arisen in this potential nervous system precursor, supporting that this configuration may have played a role as a proto-neural system and requires further investigation. PMID:26441620

  9. Event-related potentials reveal early activation of syntax information in Chinese verb processing.

    PubMed

    Deng, Yuan; Wu, Qiuyan; Wang, Jin; Feng, Liping; Xiao, Qing

    2016-09-19

    By taking advantage of the semantic-syntactic characteristics of Chinese verbs, the current study examined the brain activity of automatic activation of syntactic features at the single word level. Both syntactic (transitivity) and semantic (integrity) features of the verb were manipulated. Event-related potentials were measured while subjects performed lexical decision tasks on visually presented verbs at the single word level. The results showed that there was a significant transitivity effect in both lateral and midline areas for the 150-200ms time window (N200 effect), indicating the retrieval of the syntactic feature. There was also a significant syntactic-semantic interaction at the late stage of verb processing (N400 effect) in the midline central-parietal region, reflecting syntactic influences on semantic processing. These findings suggest that transitivity is an integral part of the mental representation of Chinese verbs and such information can be retrieved at the early stage of single verb processing and can influence subsequent semantic integration. These results also reveal the special features of Chinese language processing. PMID:27466021

  10. Event-related potentials reveal early activation of syntax information in Chinese verb processing.

    PubMed

    Deng, Yuan; Wu, Qiuyan; Wang, Jin; Feng, Liping; Xiao, Qing

    2016-09-19

    By taking advantage of the semantic-syntactic characteristics of Chinese verbs, the current study examined the brain activity of automatic activation of syntactic features at the single word level. Both syntactic (transitivity) and semantic (integrity) features of the verb were manipulated. Event-related potentials were measured while subjects performed lexical decision tasks on visually presented verbs at the single word level. The results showed that there was a significant transitivity effect in both lateral and midline areas for the 150-200ms time window (N200 effect), indicating the retrieval of the syntactic feature. There was also a significant syntactic-semantic interaction at the late stage of verb processing (N400 effect) in the midline central-parietal region, reflecting syntactic influences on semantic processing. These findings suggest that transitivity is an integral part of the mental representation of Chinese verbs and such information can be retrieved at the early stage of single verb processing and can influence subsequent semantic integration. These results also reveal the special features of Chinese language processing.

  11. Activation of GATA4 gene expression at the early stage of cardiac specification

    NASA Astrophysics Data System (ADS)

    Yilbas, Ayse; Hamilton, Alison; Wang, Yingjian; Mach, Hymn; Lacroix, Natascha; Davis, Darryl; Chen, Jihong; LI, Qiao

    2014-03-01

    Currently, there are no effective treatments to directly repair damaged heart tissue after cardiac injury since existing therapies focus on rescuing or preserving reversibly damaged tissue. Cell-based therapies using cardiomyocytes generated from stem cells present a promising therapeutic approach to directly replace damaged myocardium with new healthy tissue. However, the molecular mechanisms underlying the commitment of stem cells into cardiomyocytes are not fully understood and will be critical to guide this new technology into the clinic. Since GATA4 is a critical regulator of cardiac differentiation, we examined the molecular basis underlying the early activation of GATA4 gene expression during cardiac differentiation of pluripotent stem cells. Our studies demonstrate the direct involvement of histone acetylation and transcriptional coactivator p300 in the regulation of GATA4 gene expression. More importantly, we show that histone acetyltransferase (HAT) activity is important for GATA4 gene expression with the use of curcumin, a HAT inhibitor. In addition, the widely used histone deacetylase inhibitor valproic acid enhances both histone acetylation and cardiac specification.

  12. An NF-κB and Slug Regulatory Loop Active in Early Vertebrate Mesoderm

    PubMed Central

    Zhang, Chi; Carl, Timothy F.; Trudeau, Evan D.; Simmet, Thomas; Klymkowsky, Michael W.

    2006-01-01

    Background In both Drosophila and the mouse, the zinc finger transcription factor Snail is required for mesoderm formation; its vertebrate paralog Slug (Snai2) appears to be required for neural crest formation in the chick and the clawed frog Xenopus laevis. Both Slug and Snail act to induce epithelial to mesenchymal transition (EMT) and to suppress apoptosis. Methodology & Principle Findings Morpholino-based loss of function studies indicate that Slug is required for the normal expression of both mesodermal and neural crest markers in X. laevis. Both phenotypes are rescued by injection of RNA encoding the anti-apoptotic protein Bcl-xL; Bcl-xL's effects are dependent upon IκB kinase-mediated activation of the bipartite transcription factor NF-κB. NF-κB, in turn, directly up-regulates levels of Slug and Snail RNAs. Slug indirectly up-regulates levels of RNAs encoding the NF-κB subunit proteins RelA, Rel2, and Rel3, and directly down-regulates levels of the pro-apopotic Caspase-9 RNA. Conclusions/Significance These studies reveal a Slug/Snail–NF-κB regulatory circuit, analogous to that present in the early Drosophila embryo, active during mesodermal formation in Xenopus. This is a regulatory interaction of significance both in development and in the course of inflammatory and metastatic disease. PMID:17205110

  13. Nuclear translocation of phospholipase C-zeta, an egg-activating factor, during early embryonic development

    SciTech Connect

    Sone, Yoshie; Ito, Masahiko; Shirakawa, Hideki; Shikano, Tomohide; Takeuchi, Hiroyuki; Kinoshita, Katsuyuki; Miyazaki, Shunichi . E-mail: shunm@research.twmu.ac.jp

    2005-05-13

    Phospholipase C-zeta (PLC{zeta}), a strong candidate of the egg-activating sperm factor, causes intracellular Ca{sup 2+} oscillations and egg activation, and is subsequently accumulated into the pronucleus (PN), when expressed in mouse eggs by injection of RNA encoding PLC{zeta}. Changes in the localization of expressed PLC{zeta} were investigated by tagging with a fluorescent protein. PLC{zeta} began to translocate into the PN formed at 5-6 h after RNA injection and increased there. Observation in the same embryo revealed that PLC{zeta} in the PN dispersed to the cytoplasm upon nuclear envelope breakdown and translocated again into the nucleus after cleavage. The dynamics was found in the second mitosis as well. When RNA was injected into fertilization-originated 1-cell embryos or blastomere(s) of 2-8-cell embryos, the nuclear localization of expressed PLC{zeta} was recognized in every embryo up to blastocyst. Thus, PLC{zeta} exhibited alternative cytoplasm/nucleus localization during development. This supports the view that the sperm factor could control cell cycle-dependent generation of Ca{sup 2+} oscillations in early embryogenesis.

  14. Naturally occurring secoiridoids and bioactivity of naturally occurring iridoids and secoiridoids. A review, part 2.

    PubMed

    Dinda, Biswanath; Debnath, Sudhan; Harigaya, Yoshihiro

    2007-05-01

    Naturally occurring new secoiridoids published during 1994-2005 are reviewed with available physical and spectral data: mp, [alpha](D), UV, IR, (1)H- and (13)C-NMR and plant source. The works on biological and pharmacological activity of naturally occurring iridoids and secoiridoids reported during 1998-2005 are also reviewed. Bioactivities like antiallergic, antiarthritis, antibacterial, anticancer, anticoagulant, anticomplement, antifungal, antiinflammatory, antioxidative, antiprotozoal, antispasmodic, antiviral, immunomodulatory, neuroprotective, nerve growth factor potentiating and wound healing activities are highlighted.

  15. Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases

    PubMed Central

    Lintner, Katherine E.; Wu, Yee Ling; Yang, Yan; Spencer, Charles H.; Hauptmann, Georges; Hebert, Lee A.; Atkinson, John P.; Yu, C. Yung

    2016-01-01

    The complement system consists of effector proteins, regulators, and receptors that participate in host defense against pathogens. Activation of the complement system, via the classical pathway (CP), has long been recognized in immune complex-mediated tissue injury, most notably systemic lupus erythematosus (SLE). Paradoxically, a complete deficiency of an early component of the CP, as evidenced by homozygous genetic deficiencies reported in human, are strongly associated with the risk of developing SLE or a lupus-like disease. Similarly, isotype deficiency attributable to a gene copy-number (GCN) variation and/or the presence of autoantibodies directed against a CP component or a regulatory protein that result in an acquired deficiency are relatively common in SLE patients. Applying accurate assay methodologies with rigorous data validations, low GCNs of total C4, and heterozygous and homozygous deficiencies of C4A have been shown as medium to large effect size risk factors, while high copy numbers of total C4 or C4A as prevalent protective factors, of European and East-Asian SLE. Here, we summarize the current knowledge related to genetic deficiency and insufficiency, and acquired protein deficiencies for C1q, C1r, C1s, C4A/C4B, and C2 in disease pathogenesis and prognosis of SLE, and, briefly, for other systemic autoimmune diseases. As the complement system is increasingly found to be associated with autoimmune diseases and immune-mediated diseases, it has become an attractive therapeutic target. We highlight the recent developments and offer a balanced perspective concerning future investigations and therapeutic applications with a focus on early components of the CP in human systemic autoimmune diseases. PMID:26913032

  16. Can psychosine and galactocerebrosidase activity predict early-infantile Krabbe's disease presymptomatically?

    PubMed

    Carter, Randy L; Wrabetz, Lawrence; Jalal, Kabir; Orsini, Joseph J; Barczykowski, Amy L; Matern, Dietrich; Langan, Thomas J

    2016-11-01

    Krabbe's disease (KD) is a fatal neurodegenerative disorder, with the early-infantile form (EIKD) defined by onset of symptoms before age 6 months. Early and highly accurate identification of EIKD is required to maximize benefits of hematopoietic stem cell transplantation treatment. This study investigates the potential for accurate prediction of EIKD based on a novel newborn screening (NBS) tool developed from two biomarkers, galactocerebrosidase (GALC) enzyme activity and galactosylsphingosine concentration (psychosine [PSY]). Normative information about PSY and GALC, derived from distinct samples of normal newborns, was used to develop the novel diagnostic tool. Bivariate normal limits (BVNL) were constructed, assuming a multivariate normal distribution of natural logarithms of GALC and PSY of normal newborns. The (lnGALC, lnPSY) points for newborns in various "abnormal groups," including one group of infants who subsequently suffered EIKD, were plotted on a graph of BVNL. The points for all EIKD patients fell outside of BVNL (100% sensitivity). In a simulation study to compare the false-positive rate of existing univariate methods of diagnosis with our new BVNL-based method, we generated 100 million normal newborn data points. All fell within BVNL (i.e., zero false positives), whereas 5,682 false positives were observed when applying a two-tiered univariate method of the type suggested in the literature. These results suggest that (lnGALC, lnPSY) BVNLs will allow highly accurate prediction of EIKD, whereas two-tiered univariate approaches will not. Redevelopment of the BVNL based on GALCs and PSYs measured on a common large sample of normal newborns is required for NBS use. © 2016 Wiley Periodicals, Inc. PMID:27638594

  17. Can psychosine and galactocerebrosidase activity predict early-infantile Krabbe's disease presymptomatically?

    PubMed

    Carter, Randy L; Wrabetz, Lawrence; Jalal, Kabir; Orsini, Joseph J; Barczykowski, Amy L; Matern, Dietrich; Langan, Thomas J

    2016-11-01

    Krabbe's disease (KD) is a fatal neurodegenerative disorder, with the early-infantile form (EIKD) defined by onset of symptoms before age 6 months. Early and highly accurate identification of EIKD is required to maximize benefits of hematopoietic stem cell transplantation treatment. This study investigates the potential for accurate prediction of EIKD based on a novel newborn screening (NBS) tool developed from two biomarkers, galactocerebrosidase (GALC) enzyme activity and galactosylsphingosine concentration (psychosine [PSY]). Normative information about PSY and GALC, derived from distinct samples of normal newborns, was used to develop the novel diagnostic tool. Bivariate normal limits (BVNL) were constructed, assuming a multivariate normal distribution of natural logarithms of GALC and PSY of normal newborns. The (lnGALC, lnPSY) points for newborns in various "abnormal groups," including one group of infants who subsequently suffered EIKD, were plotted on a graph of BVNL. The points for all EIKD patients fell outside of BVNL (100% sensitivity). In a simulation study to compare the false-positive rate of existing univariate methods of diagnosis with our new BVNL-based method, we generated 100 million normal newborn data points. All fell within BVNL (i.e., zero false positives), whereas 5,682 false positives were observed when applying a two-tiered univariate method of the type suggested in the literature. These results suggest that (lnGALC, lnPSY) BVNLs will allow highly accurate prediction of EIKD, whereas two-tiered univariate approaches will not. Redevelopment of the BVNL based on GALCs and PSYs measured on a common large sample of normal newborns is required for NBS use. © 2016 Wiley Periodicals, Inc.

  18. Experimental study of possible involvement of some apoptosis mechanisms in pathogenesis of the HIV infection: 2. The CD4+ T lymphocytes depletion in the HIV infection occurs through activation-induced apoptosis.

    PubMed

    Topârceanu, F; Bârnaure, F; Iucu, C T; Spulbăr, E; Pătru, C

    1999-01-01

    The present work is a part of a complex experimental study aimed at the demonstration of the two previously published hypotheses regarding the involvement of apoptosis in general in the viral infection and especially in HIV infection (1). Our researches have shown that the significant lowering of the number of peripheral CD4+ T lymphocytes in HIV-infected children is associated with a marked increase of the soluble interleukin 2-receptor (sIL2-R)# concentration, in comparison with HIV-negative, healthy or acute infections exhibiting controls. As sIL-2R is a circulating marker of cell activation, we investigated the role of monocytes (antigen-presenting cells) in the viability of peripheral lymphocytes isolated from HIV-infected children in comparison with the controls. Lymphocytes cultivation in the absence and in the presence of autologous monocytes led to the following conclusions: 1) freshly isolated lymphocytes from HIV-positive individuals undergo an accelerated spontaneous apoptosis in comparison with that of lymphocytes isolated from HIV-negative individuals: 2) the normal antiapoptotic effect of monocytes on lymphocytes diminishes gradually in the HIV infection, changing into a proapoptotic effect, corresponding to the sIL-2R augmentation to increasingly higher values. Our results show that peripheral CD4+ T-lymphocyte depletion in HIV infection occurs through apoptosis and the activation-induced cell death is one of the possible apoptosis mechanisms.

  19. Serum copper and ceruloplasmin activity at the early growing stage in foals.

    PubMed Central

    Okumura, M; Asano, M; Tagami, M; Tsukiyama, K; Fujinaga, T

    1998-01-01

    Serum concentrations of copper (Cu), zinc (Zn), manganese (Mn), calcium (Ca) and inorganic phosphorus (P), as well as antigenic ceruloplasmin (Cp) and oxidase activity as a functional index for copper metabolism, were measured in 10 foals (5 males and 5 females) and their dams. Samples were harvested from the foals within 1 wk after birth and monthly from 1 to 17 mo of age. Samples were collected from their dams in the perinatal period (monthly from 2 mo before delivery to 5 mo postpartum). Serum oxidase activity, antigenic Cp and Cu in foals were extremely low at 1 wk. Serum Cp had the lowest value of 17.0 +/- 8.0 (mean +/- SD) mg/dL within the 1st wk, then increased rapidly up to 43.7 +/- 5.8 mg/dL at 1 mo, and maintained this level until the 17th mo. Serum Zn in foals had the highest value of 73.2 +/- 13.1 micrograms/dL within 1 wk, then decreased to 38.3 +/- 5.9 micrograms/dL by 17 mo. Serum Mn, Ca and P in mares were almost stable and within established reference ranges for our laboratory in the perinatal period, and these values in foals were also in the normal range. Even on appropriate feeding, serum Cu, Cp and oxidase activity were quite low a few weeks after birth, while a higher proportion of Cp-binding copper was found in the foals. This might be caused by the limited synthesis of ceruloplasmin in this period. These data suggest that newborn foals are in a critical situation of marginal copper status in the early stage of growth. PMID:9553711

  20. Interleukin 8 is differently expressed and modulated by PAR-1 activation in early and late endothelial progenitor cells.

    PubMed

    Smadja, David M; Bièche, Ivan; Susen, Sophie; Mauge, Laetitia; Laurendeau, Ingrid; d'Audigier, Clément; Grelac, Françoise; Emmerich, Joseph; Aiach, Martine; Gaussem, Pascale

    2009-08-01

    The proinflammatory chemokine interleukin 8 exerts potent angiogenic effects on endothelial cells by interacting with its receptors CXCR1 and CXCR2. As thrombin is also a potent inflammatory factor, and as endothelial progenitor cells (EPC) express functional PAR-1 thrombin receptor, we examined whether PAR-1 stimulation interferes with the IL-8 pathway in EPC. EPC were obtained from adult blood (AB) and cord blood (CB). The effect of PAR-1 stimulation by the peptide SFLLRN on IL-8, CXCR1 and CXCR2 expression was examined by RTQ-PCR and at the protein level in AB and CB late EPC and in AB early EPC. Specific siRNA was used to knock down PAR-1 expression. The IL-8 gene was expressed strongly in AB early EPC and moderately in late EPC. In contrast, CXCR1 and CXCR2 gene expression was restricted to AB early EPC. The IL-8 level in AB early EPC conditioned medium was high in basal conditions and did not change after PAR-1 activation. By contrast, IL-8 secretion by late EPC was low in basal conditions and strongly up-regulated upon PAR-1 activation. PAR-1 activation induced a number of genes involved in activating protein-1 (AP-1) and nuclear factor (NF)-kappaB pathways. Conditioned medium of PAR-1-activated late EPC enhanced the migratory potential of early EPC, and this effect was abrogated by blocking IL-8. Target-specific siRNA-induced PAR-1 knockdown, and fully inhibited PAR-1-induced IL-8 synthesis. In conclusion, PAR-1 activation induces IL-8 synthesis by late EPC. This could potentially enhance cooperation between late and early EPC during neovascularization, through a paracrine effect. PMID:18657231

  1. A Naturally Occurring Mutation K220T in the Pleiotropic Activator PrfA of Listeria Monocytogenes Results in a Loss of Virulence Due to Decreasing DNA-Binding Affinity

    SciTech Connect

    Velge,P.; Herler, M.; Johansson, J.; Roches, S.; Temoin, S.; Fedorov, A.; Gracieux, P.; Almo, S.; Goebel, W.; Cossart, P.

    2007-01-01

    The sequencing of prfA, encoding the transcriptional regulator of virulence genes, in 26 low-virulence field Listeria monocytogenes strains showed that eight strains exhibited the same single amino-acid substitution: PrfAK220T. These strains exhibited no expression of PrfA-regulated proteins and thus no virulence. This substitution inactivated PrfA, since expression of the PrfAK220T mutant gene in an EGD{Delta}prfA strain did not restore the haemolytic and phosphatidylcholine phospholipase C activities, in contrast to the wild-type prfA gene. The substitution of the lysine at position 220 occurred in the helix H. However, the data showed that the PrfAK220T protein is dimerized just as well as its wild-type counterpart, but does not bind to PrfA-boxes. PrfAK220T did not form a PrfA-DNA complex in electrophoretic mobility shift assays, but low concentrations of CI complexes (PrfAK220T-RNA polymerase-DNA complex) were formed by adding RNA polymerase, suggesting that PrfA interacted with RNA polymerase in solution in the absence of DNA. Formation of some transcriptionally active complexes was confirmed by in vitro runoff transcription assays and quantitative RT-PCR. Crystallographic analyses described the structure of native PrfA and highlighted the key role of allosteric changes in the activity of PrfA and especially the role of the Lys220 in the conformation of the helix-turn-helix (HTH) motif.

  2. Redox cycling of a copper complex with benzaldehyde nitrogen mustard-2-pyridine carboxylic acid hydrazone contributes to its enhanced antitumor activity, but no change in the mechanism of action occurs after chelation.

    PubMed

    Yang, Yinli; Li, Cuiping; Fu, Yun; Liu, Youxun; Zhang, Yu; Zhang, Yanfang; Zhou, Pingxin; Yuan, Yanbin; Zhou, Sufeng; Li, Shaoshan; Li, Changzheng

    2016-03-01

    Many anticancer drugs used in the clinical have potent metal chelating ability. The formed metal complex(es) may exhibit improved (or antagonistic) antitumor activity. However, the underlying mechanism has received limited attention. Therefore, investigation of the mechanism involved in the change upon chelation is required to extend our understanding of the effects of various drugs. In the present study, the proliferation inhibition effect of benzaldehyde nitrogen mustard-2-pyridine carboxylic acid hydrazone (BNMPH) and its copper complex on tumor cell lines was investigated. The copper chelate exhibited almost a 10-fold increase in antitumor activity (with IC50 <5 µM). The results showed that both BNMPH and its copper complex induced reactive oxygen species (ROS) generation, and caused upregulation of caspase 8 and Bax as well as the downregulation of Bcl-2, indicating that apoptosis was involved in the cytotoxic effects. DNA fragmentation noted in the comet assay further supported ROS involvement. The present study indicated that BNMPH and its copper complex effectively induced S phase arrest and the cell cycle arrest was associated with the downregulation of cyclin D1. The formation of acidic vesicular organelles (AVOs) and an increase in cleaved LC3-II demonstrated that autophagy occurred in the HepG2 cells treated with the agents. Taken together, BNMPH and its copper complex exhibited proliferation inhibition via apoptosis, cell cycle arrest and autophagy, which was dependent on ROS. The enhanced antitumor activity of the copper complex was due to its redox-cycling ability, but the mechanism was not altered compared to BNMPH. Our findings may significantly contribute to the understanding of the anti-proliferative effect of BNMPH and its copper complex.

  3. Cell-specific activity of the modulator region in the human cytomegalovirus major immediate-early gene

    SciTech Connect

    Lubon, H.K.; Hennighausen, L. ); Ghazal, P.; Reynolds-Kohler, C.; Lockshin, C.; Nelson, J. )

    1989-03-01

    In this paper the authors demonstrate that modular sequences upstream of the enhancer of the major immediate-early promoter of human cytomegalovirus exert a differential effort on the level of transcription in a variety of cells and that this region has the capacity to interact with specific nuclear protein. Depending on the cell type, these modulator sequences increased or decreased transcriptional activation from the IE1 gene promoter-enhancer. The cell lines identified in this report should be useful to study the molecular mechanism of cell-specific transcriptional repression and activation exerted by the major immediate-early promoter upstream region.

  4. Sensory-motor transformations for speech occur bilaterally.

    PubMed

    Cogan, Gregory B; Thesen, Thomas; Carlson, Chad; Doyle, Werner; Devinsky, Orrin; Pesaran, Bijan

    2014-03-01

    Historically, the study of speech processing has emphasized a strong link between auditory perceptual input and motor production output. A kind of 'parity' is essential, as both perception- and production-based representations must form a unified interface to facilitate access to higher-order language processes such as syntax and semantics, believed to be computed in the dominant, typically left hemisphere. Although various theories have been proposed to unite perception and production, the underlying neural mechanisms are unclear. Early models of speech and language processing proposed that perceptual processing occurred in the left posterior superior temporal gyrus (Wernicke's area) and motor production processes occurred in the left inferior frontal gyrus (Broca's area). Sensory activity was proposed to link to production activity through connecting fibre tracts, forming the left lateralized speech sensory-motor system. Although recent evidence indicates that speech perception occurs bilaterally, prevailing models maintain that the speech sensory-motor system is left lateralized and facilitates the transformation from sensory-based auditory representations to motor-based production representations. However, evidence for the lateralized computation of sensory-motor speech transformations is indirect and primarily comes from stroke patients that have speech repetition deficits (conduction aphasia) and studies using covert speech and haemodynamic functional imaging. Whether the speech sensory-motor system is lateralized, like higher-order language processes, or bilateral, like speech perception, is controversial. Here we use direct neural recordings in subjects performing sensory-motor tasks involving overt speech production to show that sensory-motor transformations occur bilaterally. We demonstrate that electrodes over bilateral inferior frontal, inferior parietal, superior temporal, premotor and somatosensory cortices exhibit robust sensory-motor neural

  5. Sensory-motor transformations for speech occur bilaterally.

    PubMed

    Cogan, Gregory B; Thesen, Thomas; Carlson, Chad; Doyle, Werner; Devinsky, Orrin; Pesaran, Bijan

    2014-03-01

    Historically, the study of speech processing has emphasized a strong link between auditory perceptual input and motor production output. A kind of 'parity' is essential, as both perception- and production-based representations must form a unified interface to facilitate access to higher-order language processes such as syntax and semantics, believed to be computed in the dominant, typically left hemisphere. Although various theories have been proposed to unite perception and production, the underlying neural mechanisms are unclear. Early models of speech and language processing proposed that perceptual processing occurred in the left posterior superior temporal gyrus (Wernicke's area) and motor production processes occurred in the left inferior frontal gyrus (Broca's area). Sensory activity was proposed to link to production activity through connecting fibre tracts, forming the left lateralized speech sensory-motor system. Although recent evidence indicates that speech perception occurs bilaterally, prevailing models maintain that the speech sensory-motor system is left lateralized and facilitates the transformation from sensory-based auditory representations to motor-based production representations. However, evidence for the lateralized computation of sensory-motor speech transformations is indirect and primarily comes from stroke patients that have speech repetition deficits (conduction aphasia) and studies using covert speech and haemodynamic functional imaging. Whether the speech sensory-motor system is lateralized, like higher-order language processes, or bilateral, like speech perception, is controversial. Here we use direct neural recordings in subjects performing sensory-motor tasks involving overt speech production to show that sensory-motor transformations occur bilaterally. We demonstrate that electrodes over bilateral inferior frontal, inferior parietal, superior temporal, premotor and somatosensory cortices exhibit robust sensory-motor neural

  6. Early Activation of the Kynurenine Pathway Predicts Early Death and Long‐term Outcome in Patients Resuscitated From Out‐of‐Hospital Cardiac Arrest

    PubMed Central

    Ristagno, Giuseppe; Latini, Roberto; Vaahersalo, Jukka; Masson, Serge; Kurola, Jouni; Varpula, Tero; Lucchetti, Jacopo; Fracasso, Claudia; Guiso, Giovanna; Montanelli, Alessandro; Barlera, Simona; Gobbi, Marco; Tiainen, Marjaana; Pettilä, Ville; Skrifvars, Markus B.

    2014-01-01

    Background The kynurenine pathway (KP) is the major route of tryptophan (TRP) catabolism and is activated by inflammation and after cardiac arrest in animals. We hypothesized that the KP activation level correlates with severity of post–cardiac arrest shock, early death, and long‐term outcome. Methods and Results Plasma was obtained from 245 patients enrolled in a prospective multicenter observational study in 21 intensive care units in Finland. Time to return of spontaneous circulation, lowest systolic arterial pressure, and bicarbonate during the first 24 hours were collected. A cerebral performance category of 3 to 5 defined 12‐month poor outcome. Plasma TRP and KP metabolites, kynurenine (KYN), kynurenic acid, 3‐hydroxyanthranilic acid, and the ratio of KYN to TRP were measured by liquid chromatography and mass spectrometry. All KP metabolites at intensive care unit admission were significantly higher in cardiac arrest patients with a nonshockable rhythm compared to those with a shockable rhythm, and kynurenic acid and 3‐hydroxyanthranilic acid correlated with time to return of spontaneous circulation. Patients with higher levels of KYN, KYN to TRP, kynurenic acid, and 3‐hydroxyanthranilic acid had lower 24‐hour systolic arterial pressure and bicarbonate. All KP metabolites and the ratio of KYN to TRP, but not TRP, were significantly higher in patients who died in the intensive care unit in comparison to those who survived. Multivariable logistic regression showed that high kynurenic acid (odds ratio: 1.004; 95% confidence interval: 1.001 to 1.008; P=0.014), and 3‐hydroxyanthranilic acid (odds ratio: 1.011; 95% confidence interval: 1.001 to 1.022; P=0.03) were independently associated with 12‐month poor outcome and significantly improved risk reclassification. Conclusions KP is activated early after cardiac arrest and is associated with severity of post–cardiac arrest shock, early death, and poor long‐term outcome. PMID:25092787

  7. Early activation of p38 mitogen activated protein kinase is associated with interferon-alpha-induced depression and fatigue

    PubMed Central

    Felger, Jennifer C.; Alagbe, Oyetunde; Pace, Thaddeus W. W.; Woolwine, Bobbi J.; Hu, Fang; Raison, Charles L.; Miller, Andrew H.

    2011-01-01

    Cytokine-induced stimulation of p38 mitogen activated protein kinase (MAPK) has been shown to influence behaviorally-relevant pathophysiologic pathways including monoamine neurotransmission and neuroendocrine function and thus may contribute to behavioral changes that occur during chronic administration of the innate immune cytokine, interferon (IFN)-alpha. Accordingly, in the current study, phosphorylation (activation) of intracellular p38 MAPK in peripheral blood lymphocytes was analyzed by flow cytometry every 2 hours for 12 hours following the initial injection of IFN-alpha in eleven patients with chronic hepatitis C. Hourly assessments of plasma concentrations of adrenocorticotropic hormone, cortisol and interleukin-6 were also obtained. Symptoms of depression and fatigue were measured at baseline and after 4 and 12 weeks of IFN-alpha treatment. Acute administration of IFN-alpha significantly increased the percentage of lymphocytes staining positive for intracellular phosphorylated p38 (p-p38). IFN-alpha-induced increases in p-p38 were significantly greater in patients that developed clinically significant depressive symptoms [Montgomery Asberg Depression Rating Scale (MADRS) score ≥15] during the first 12 weeks of IFN-alpha treatment. Increases in the percentage of p-p38-positive lymphocytes following the first IFN-alpha injection also highly correlated with depression severity at weeks 4 (r=0.85, p=0.001) and 12 (r=0.70, p=0.018). Similar relationships were observed for fatigue. Examination of relationships between p-p38 induction and factors previously reported to predict IFN-alpha-induced depressive symptoms revealed strong associations of p-p38 with baseline MADRS (r=0.82, p=0.002) and cortisol responses to the initial injection of IFN-alpha (r=0.91, p=0.000). Taken together, these findings indicate that sensitivity of p38 MAPK signaling pathways to immune stimulation is associated with depressive symptoms during chronic IFN-alpha treatment. PMID

  8. Feedback in the local Universe: Relation between star formation and AGN activity in early type galaxies

    NASA Astrophysics Data System (ADS)

    Vaddi, Sravani; O'Dea, Christopher; Baum, Stefi; Jones, Christine; Forman, William; Whitmore, Samantha; Ahmed, Rabeea; Pierce, Katherine; Leary, Sara

    2015-08-01

    Aim: We address the relation between star formation and AGN activity in a large sample of nearby early type (E and S0) galaxies. The redshift range of the galaxies is 0.0002early type galaxies which were selected to have an apparent K-band magnitude brighter than 13.5 and whose positions correlate with Chandra ACIS-I and ACIS-S sources. The galaxies in the sample are unbiased regarding their star formation and radio source properties. Using the archival observations at radio, IR and UV from VLA, WISE and GALEX respectively, we obtained the radio power, estimate FUV star formation rate (SFR) and other galaxy properties to study AGN activity and ongoing star formation.Results: The relationship between radio power and stellar mass shows that there is an upper envelope of radio power that is a steep function of stellar luminosity. This suggests that less massive galaxies have low radio power while massive galaxies are capable of hosting powerful radio sources. The Radio-MIR relation shows that galaxies with P>=1022 WHz-1 are potential candidates for being AGN. About ~ 7% of the sample show evidence of ongoing star formation with SFR ranging from 10-3 to 1 M⊙yr-1. These are also less massive and radio faint suggesting the absence of active accretion. There is nearly equal fraction of star forming galaxies in radio faint (P<1022 WHz-1) and radio bright galaxies (P>=1022 WHz-1) . Only ~ 5% of the galaxies in our sample have P>=1022 WHz-1 and most of them do not show evidence of bright accretion disks. We see a weak correlation and a dispersion of

  9. Early Activation of Teleost B Cells in Response to Rhabdovirus Infection

    PubMed Central

    Abós, Beatriz; Castro, Rosario; González Granja, Aitor; Havixbeck, Jeffrey J.; Barreda, Daniel R.

    2014-01-01

    have demonstrated that VHSV infection provoked immediate transcriptional effects on B cells, at least partially mediated by intracellular PRR signaling. VHSV also activated NF-κB and increased IgM+ cell survival. Interestingly, VHSV activated B lymphocytes toward an antigen-presenting profile, suggesting an important role of IgM+ cells in VHSV presentation. Our results provide a first description of the effects provoked by fish rhabdoviruses through their early interaction with teleost B cells. PMID:25410870

  10. REDISTRIBUTION OF ALKALINE ELEMENTS IN ASSOCIATION WITH AQUEOUS ACTIVITY IN THE EARLY SOLAR SYSTEM

    SciTech Connect

    Hidaka, Hiroshi; Higuchi, Takuya; Yoneda, Shigekazu E-mail: s-yoneda@kahaku.go.jp

    2015-12-10

    It is known that the Sayama meteorite (CM2) shows an extensive signature for aqueous alteration on the meteorite parent body, and that most of the primary minerals in the chondrules are replaced with phyllosilicates as the result of the aqueous alteration. In this paper, it is confirmed from the observation of two-dimensional Raman spectra that a part of olivine in a chondrule collected from the Sayama chondrite is serperntinized. Ion microprobe analysis of the chondrule showed that alkaline elements such as Rb and Cs are heterogeneously redistributed in the chondrule. The result of higher Rb and Cs contents in serpentinized phases in the chondrule rather than in other parts suggested the selective adsorption of alkaline elements into the serpentine in association with early aqueous activity on the meteorite parent body. Furthermore Ba isotopic analysis provided variations of {sup 135}Ba/{sup 138}Ba and {sup 137}Ba/{sup 138}Ba in the chondrule. This result was consistent with our previous isotopic data suggesting isotopic evidence for the existence of the presently extinct nuclide {sup 135}Cs in the Sayama meteorite, but the abundance of {sup 135}Cs in the solar system remains unclear because of large analytical uncertainties.

  11. Early Local Activity in Temporal Areas Reflects Graded Content of Visual Perception.

    PubMed

    Tagliabue, Chiara F; Mazzi, Chiara; Bagattini, Chiara; Savazzi, Silvia

    2016-01-01

    In visual cognitive neuroscience the debate on consciousness is focused on two major topics: the search for the neural correlates of the different properties of visual awareness and the controversy on the graded versus dichotomous nature of visual conscious experience. The aim of this study is to search for the possible neural correlates of different grades of visual awareness investigating the Event Related Potentials to reduced contrast visual stimuli whose perceptual clarity was rated on the four-point Perceptual Awareness Scale. Results revealed a left centro-parietal negative deflection (Visual Awareness Negativity; VAN) peaking at 280-320 ms from stimulus onset, related to the perceptual content of the stimulus, followed by a bilateral positive deflection (Late Positivity; LP) peaking at 510-550 ms over almost all electrodes, reflecting post-perceptual processes performed on such content. Interestingly, the amplitude of both deflections gradually increased as a function of visual awareness. Moreover, the intracranial generators of the phenomenal content (VAN) were found to be located in the left temporal lobe. The present data thus seem to suggest (1) that visual conscious experience is characterized by a gradual increase of perceived clarity at both behavioral and neural level and (2) that the actual content of perceptual experiences emerges from early local activation in temporal areas, without the need of later widespread frontal engagement. PMID:27199809

  12. Early Local Activity in Temporal Areas Reflects Graded Content of Visual Perception

    PubMed Central

    Tagliabue, Chiara F.; Mazzi, Chiara; Bagattini, Chiara; Savazzi, Silvia

    2016-01-01

    In visual cognitive neuroscience the debate on consciousness is focused on two major topics: the search for the neural correlates of the different properties of visual awareness and the controversy on the graded versus dichotomous nature of visual conscious experience. The aim of this study is to search for the possible neural correlates of different grades of visual awareness investigating the Event Related Potentials to reduced contrast visual stimuli whose perceptual clarity was rated on the four-point Perceptual Awareness Scale. Results revealed a left centro-parietal negative deflection (Visual Awareness Negativity; VAN) peaking at 280–320 ms from stimulus onset, related to the perceptual content of the stimulus, followed by a bilateral positive deflection (Late Positivity; LP) peaking at 510–550 ms over almost all electrodes, reflecting post-perceptual processes performed on such content. Interestingly, the amplitude of both deflections gradually increased as a function of visual awareness. Moreover, the intracranial generators of the phenomenal content (VAN) were found to be located in the left temporal lobe. The present data thus seem to suggest (1) that visual conscious experience is characterized by a gradual increase of perceived clarity at both behavioral and neural level and (2) that the actual content of perceptual experiences emerges from early local activation in temporal areas, without the need of later widespread frontal engagement. PMID:27199809

  13. New Insights on Late-A and Early-F Star Activity

    NASA Astrophysics Data System (ADS)

    Freire Ferrero, R.; Catalano, S.; Marilli, E.; Gouttebroze, P.; Talavera, A.; Bruhweiler, F.

    The onset of chromospheric activity in late-A and early-F stars is here discussed. The detection of Ly- emission core in several A and F atars with the IUE satellite, gives evidence for the presence of chromospheric layers in these stars up to B - V = 0m.19 (Marilli et al., 1996). Semiempirical chromospheric models for Altair allowed us (Freire Ferrero et al., 1995) to explain the observed emission profiles taking into account normal H I interstellar (IS) absorption. However, due to the very high rotational velocity, we analysed alternative hypotheses to explain the observed emissions: (1) circumstellar or shell matter; (2) co-rotating expanding optically thin wind. We ruled out these hypotheses because their effects are negligible and as a consequence, this result reinforces the chromospheric origin of the observed Ly- core in Altair. The stars of our sample, having observed Ly- profilies similar to Altair's and similar stellar and IS properties, should reproduce similar chromospheric behaviour. Here we discuss several important questions that are raised by these results.

  14. The fungicide imazalil induces developmental abnormalities and alters locomotor activity during early developmental stages in zebrafish.

    PubMed

    Jin, Yuanxiang; Zhu, Zhihong; Wang, Yueyi; Yang, Enlu; Feng, Xiayan; Fu, Zhengwei

    2016-06-01

    The fungicide imazalil (IMZ) is used extensively to protect vegetable fields, fruit plantations and post-harvest crops from rot. Likely due to its wide-spread use, IMZ is frequently detected in vegetable, fruit, soil and even surface water samples. Even though several previous studies have reported on the neurotoxicity of IMZ, its effects on the neurobehavior of zebrafish have received little attention to date. In this study, we show that the heartbeat and hatchability of zebrafish were significantly influenced by IMZ concentrations of 300 μg L(-1) or higher. Moreover, in zebrafish larvae, locomotor behaviors such as average swimming speed and swimming distance were significantly decreased after exposure to 300 μg L(-1) IMZ for 96 h, and acetylcholinesterase (AChE) expression and activity were consistently inhibited in IMZ-treated fish. Our results further suggest that IMZ could act as a neuroendocrine disruptor by decreasing the expression of neurotoxicity-related genes such as Glial fibrillary acidic protein (Gfap), Myelin basic protein (Mbp) and Sonic hedgehog a (Shha) during early developmental stages of zebrafish. In conclusion, we show that exposure to IMZ has the potential to induce developmental toxicity and locomotor behavior abnormalities during zebrafish development. PMID:27035382

  15. Disease activity and severity in early inflammatory arthritis predict hand cortical bone loss

    PubMed Central

    Pye, Stephen R.; Adams, Judith E.; Ward, Kate A.; Bunn, Diane K.; Symmons, Deborah P. M.

    2010-01-01

    Objectives. To determine the influence of disease-related variables on hand cortical bone loss in women with early inflammatory arthritis (IA), and whether hand cortical bone mass predicts subsequent joint damage. Method. Adults aged ≥16 years with recent onset of IA were recruited to the Norfolk Arthritis Register between 1990 and 1998, and followed prospectively. At baseline, patients had their joints examined for swelling and tenderness and had CRP and disease activity 28-joint assessment score (DAS-28) measured. Radiographs of the hands were performed in a subgroup of patients at Year 1 and at follow-up, which were assessed using digital X-ray radiogrammetry (DXR). They were also evaluated for the presence of erosions using Larsen’s method. Linear mixed models were used to investigate whether disease-related factors predicted change in DXR–areal bone mineral density (BMDa). We also evaluated whether DXR–BMDa predicted the subsequent occurrence of erosive disease. Results. Two hundred and four women, mean (s.d.) age 55.1 (14.0) years, were included. Median follow-up between radiographs was 4 years. The mean within-subject change in BMDa was 0.024 g/cm2 equivalent to 1% decline per year. After adjustment for age, height and weight, compared with those within the lower tertile for CRP, those in the upper tertile had greater subsequent loss of bone. This was true also for DAS-28 and Larsen score. Among those without erosions on the initial radiograph (121), DXR–BMDa at baseline did not predict the new occurrence of erosions. Conclusion. Increased disease activity and severity are associated with accelerated bone loss. However, lower BMDa did not predict the new occurrence of erosive disease. PMID:20573690

  16. Ring current activity during the early Bz<0 phase of the January 1997 magnetic cloud

    NASA Astrophysics Data System (ADS)

    Jordanova, V. K.; Torbert, R. B.; Thorne, R. M.; Collin, H. L.; Roeder, J. L.; Foster, J. C.

    1999-11-01

    The passage at Earth of the January 10-11, 1997, magnetic cloud induced a storm of moderate geomagnetic activity with Dst index reaching minimum values of about -83 nT. We study ring current formation during the early Bz negative phase of this magnetic cloud, using energetic particle data from three instruments on the Polar spacecraft and geosynchronous plasma data from the LANL spacecraft. We use our kinetic drift-loss model to simulate the evolution of ring current H+, He+, and O+ ion distributions and associated aeronomical effects during this period. The results from two Volland-Stern type magnetospheric electric field model formulations are compared: (1) Kp-dependent and (2) interplanetary magnetic field (IMF) dependent. We demonstrate that while both electric field models reproduce well the main trends of ring current formation and decay during the storm, the IMF-dependent model reproduces the rapidity of the main storm growth phase and its strength better. Comparing model results during the main phase of the storm with HYDRA, TIMAS, and CAMMICE data we find that the model reproduces very well the ring current distributions near dawn. The formation of the nose event, i.e., the rise of the 10-30 keV energy particles near dusk due to abruptly increased convection is, however, overestimated by the model. We compute plasmaspheric heating through Coulomb collisions as the storm evolves and find that maximum heating occurs initially on the nightside near L~3.5 and subsequently moves earthward to L~2.75, in agreement with Millstone Hill radar observations of midlatitude electron temperature enhancement on January 10. However, the magnitude of the energy transferred to plasmaspheric electrons through Coulomb collisions appears to be not sufficient to yield the observed elevated electron temperature at ~0830 UT, suggesting that additional energy sources should be considered during this event.

  17. Early cerebral activities of the environmental estrogen bisphenol A appear to act via the somatostatin receptor subtype sst(2).

    PubMed Central

    Facciolo, Rosa Maria; Alò, Raffaella; Madeo, Maria; Canonaco, Marcello; Dessì-Fulgheri, Francesco

    2002-01-01

    Recently, considerable interest has been aroused by the specific actions of bisphenol A (BPA). The present investigation represents a first study dealing with the interaction of BPA with the biologically more active somatostatin receptor subtype (sst(2)) in the rat limbic circuit. After treating pregnant female Sprague-Dawley rats with two doses (400 microg/kg/day; 40 microg/kg/day) of BPA, the binding activity of the above receptor subtype was evaluated in some limbic regions of the offspring. The higher dose proved to be the more effective one, as demonstrated by the elevated affinity of sst(2) with its specific radioligand, [(125)I]-Tyr(0)somatostatin-14. The most dramatic effects of BPA on sst(2) levels occurred at the low-affinity states of such a subtype in some telencephalic limbic areas of postnatal rats (10 days of age; postnatal day [PND] 10). These included lower (p < 0.05) sst(2) levels in the gyrus dentate of the hippocampus and basomedial nucleus of the amygdala; significantly higher (p < 0.01) levels were observed only for the high-affinity states of the periventricular nucleus of the hypothalamus. A similar trend was maintained in PND 23 rats with the exception of much lower levels of the high-affinity sst(2) receptor subtype in the amygdala nucleus and ventromedial hypothalamic nucleus. However, greater changes produced by this environmental estrogen were reported when the binding activity of sst(2) was checked in the presence of the two more important selective agonists (zolpidem and Ro 15-4513) specific for the alpha-containing Gamma-aminobutyric acid (GABA) type A receptor complex. In this case, an even greater potentiating effect (p < 0.001) was mainly obtained for the low-affinity sst(2) receptor subtype in PND 10 animals, with the exception of the high-affinity type in the ventromedial hypothalamic nucleus and gyrus dentate. These results support the contention that an sst(2) subtype alpha-containing GABA type A receptor system might

  18. Stratiform copper deposit, northern anatolia, Turkey: evidence for early bronze I (2800 B.C.) mining activity.

    PubMed

    Giles, D L; Kuijpers, E P

    1974-11-29

    A stratiform, massive copper sulfide deposit with possible gold, silver, and cobalt credits was discovered by a United Nations reconnaissance team in Paleozoic (?) metamorphic terrain of north central Turkey. The deposit, which is of possible volcanigenic exhalative origin, contains evidence of extensive prehistoric underground mining and smelting activity that, based on radiocarbon data, may date to 2800 B.C. (Early Bronze I Age).

  19. Immediate-early gene region of human cytomegalovirus trans-activates the promoter of human immunodeficiency virus

    SciTech Connect

    Davis, M.G.; Kenney, S.C.; Kamine, J.; Pagano, J.S.; Huang, E.S.

    1987-12-01

    Almost all homosexual patients with acquired immunodeficiency syndrome are also actively infected with human cytomegalovirus (HCMV). The authors have hypothesized that an interaction between HCMV and human immunodeficiency virus (HIV), the agent that causes acquired immunodeficiency syndrome, may exist at a molecular level and contribute to the manifestations of HIV infection. In this report, they demonstrate that the immediate-early gene region of HCMV, in particular immediate-early region 2, trans-activates the expression of the bacterial gene chloramphenicol acetyltransferase that is fused to the HIV long terminal repeat and carried by plasmid pHIV-CAT. The HCMV immediate-early trans-activator increases the level of mRNA from the plamid pHIV-CAT. The sequences of HIV that are responsive to trans-activation by the HDMV immediate-early region are distinct from HIV sequences that are required for response to the HIV tat. The stimulation of HIV gene expression by HDMV gene functions could enhance the consequences of HIV infection in persons with previous or concurrent HCMV infection.

  20. 7 CFR 799.7 - Early involvement in private and state and local activities requiring Federal approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Early involvement in private and state and local activities requiring Federal approval. 799.7 Section 799.7 Agriculture Regulations of the Department of Agriculture (Continued) FARM SERVICE AGENCY, DEPARTMENT OF AGRICULTURE ENVIRONMENTAL PROTECTION...

  1. 7 CFR 799.7 - Early involvement in private and state and local activities requiring Federal approval.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 7 2014-01-01 2014-01-01 false Early involvement in private and state and local activities requiring Federal approval. 799.7 Section 799.7 Agriculture Regulations of the Department of Agriculture (Continued) FARM SERVICE AGENCY, DEPARTMENT OF AGRICULTURE ENVIRONMENTAL PROTECTION...

  2. 7 CFR 799.7 - Early involvement in private and state and local activities requiring Federal approval.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 7 2011-01-01 2011-01-01 false Early involvement in private and state and local activities requiring Federal approval. 799.7 Section 799.7 Agriculture Regulations of the Department of Agriculture (Continued) FARM SERVICE AGENCY, DEPARTMENT OF AGRICULTURE ENVIRONMENTAL PROTECTION...

  3. Active Head Lifting from Supine in Early Infancy: An Indicator for Non-Optimal Cognitive Outcome in Late Infancy

    ERIC Educational Resources Information Center

    van Haastert, Ingrid C.; Groenendaal, Floris; van de Waarsenburg, Maria K.; Eijsermans, Maria J. C.; Koopman-Esseboom, Corine; Jongmans, Marian J.; Helders, Paul J. M.; de Vries, Linda S.

    2012-01-01

    Aim: To explore whether active head lifting from supine (AHLS) in early infancy is associated with cognitive outcome in the second year of life. Method: The presence of AHLS was always recorded in the notes of infants admitted to our tertiary neonatal intensive care unit. Random sampling was used to pair infants with AHLS with two comparison…

  4. Behavioral Activation as an Early Intervention for Posttraumatic Stress Disorder and Depression among Physically Injured Trauma Survivors

    ERIC Educational Resources Information Center

    Wagner, Amy W.; Zatzick, Douglas F.; Ghesquiere, Angela; Jurkovich, Gregory J.

    2007-01-01

    This paper describes an adaptation of behavioral activation (BA) for the early intervention of posttraumatic stress disorder (PTSD) and depression among physically injured survivors of traumatic injury, and presents pilot data on a small randomized effectiveness trial (N = 8). The application of BA to PTSD is based on the theory that increases in…

  5. Associations among Preschool Children's Classroom Literacy Environment, Interest and Engagement in Literacy Activities, and Early Reading Skills

    ERIC Educational Resources Information Center

    Baroody, Alison E.; Diamond, Karen E.

    2016-01-01

    This study examines the relations among the classroom literacy environment, children's interest and engagement in literacy activities, and children's early reading skills in a sample of 167 children aged 4 and 5 years enrolled in 31 Head Start classrooms. Researchers rated the classroom literacy environment. Teachers reported on children's…

  6. Caffeine, a naturally occurring acaricide.

    PubMed

    Russell, D W; Fernández-Caldas, E; Swanson, M C; Seleznick, M J; Trudeau, W L; Lockey, R F

    1991-01-01

    Since caffeine is a plant alkaloid that has been described as a naturally occurring insecticide, its acaricidal effect on Dermatophagoides pteronyssinus (Dp) was investigated. Twelve cultures were established by adding 30 Dp to 200 mg of Tetramin fish food and brewer's yeast (8:2 ratio); six cultures were treated with 20 mg of finely ground caffeine. All 12 cultures were incubated at 75% relative humidity, 25 degrees C, and observed during 8 weeks. Live mites were then counted under a stereoscope, cultures were extracted, and supernatants were analyzed for Der p I and Der f I allergen content with a two-site monoclonal RIA. Live mite counts in untreated cultures varied from 146 to 274 (215 +/- 47.1), and in caffeine-treated cultures from 0 to 3 (1 +/- 1.2; p less than or equal to 0.0001). Der p I concentrations in untreated cultures varied from 588 to 9000 ng/gm (3138.3 +/- 2990.8 ng/gm), and in caffeine-treated cultures from 52 to 117 ng/gm (78 +/- 23.8 ng/gm; p less than or equal to 0.01). Der p I was not detected in the food media or caffeine; Der f I was not detected in any of the cultures. Results demonstrate that caffeine inhibits mite growth and allergen production.

  7. Storytelling Dramas as a Community Building Activity in an Early Childhood Classroom

    ERIC Educational Resources Information Center

    Wright, Cheryl; Diener, Marissa L.; Kemp, Jacqueline Lindsay

    2013-01-01

    Healthy social-emotional development is promoted by building a safe, secure and respectful environment in an early childhood setting with positive and consistent relationships among adults, children, and their peers. This study explored storytelling dramas as an opportunity to build community within the context of one early childhood classroom.…

  8. Group Time Experiences: Belonging, Being and Becoming through Active Participation within Early Childhood Communities

    ERIC Educational Resources Information Center

    Leggett, Nicole; Ford, Margot

    2016-01-01

    The National Quality Standards (NQS) as part of the Australian National Quality Framework were developed in 2011 and included several references to the organisation of small and large groups within early childhood settings (ACECQA 2013). The NQS act in tandem with the Early Years Learning Framework (EYLF) (DEEWR 2009) and are the basis by which…

  9. Recommended Practices for Promoting Physical Activity in Early Childhood Education Settings

    ERIC Educational Resources Information Center

    Wright, Paul M.; Stork, Steve

    2013-01-01

    Although the importance of physical development as an integrated part of early childhood education is well understood, many early childhood teachers lack the specific background and training in this area. To fill this gap, this article presents a framework of recommended practices and a corresponding assessment tool. The Head Start Body Start…

  10. Knee pain during activities of daily living and its relationship with physical activity in patients with early and severe knee osteoarthritis.

    PubMed

    Fukutani, Naoto; Iijima, Hirotaka; Aoyama, Tomoki; Yamamoto, Yuko; Hiraoka, Masakazu; Miyanobu, Kazuyuki; Jinnouchi, Masashi; Kaneda, Eishi; Tsuboyama, Tadao; Matsuda, Shuichi

    2016-09-01

    This study aimed to investigate whether knee pain during various activities of daily living (ADLs) is associated with physical activity in patients with early and severe knee osteoarthritis (OA). We hypothesized that the painful ADLs associated with decreased physical activity differ according to disease severity. This cross-sectional study enrolled 270 patients with medial knee OA, assigned to either the early (Kellgren Lawrence [K/L] grade 1-2) or the severe group (K/L grade 3-4). Physical activity was assessed using a pedometer. Knee pain during six ADLs (waking up in the morning, walking on a flat surface, ascending stairs, etc.) was evaluated using a questionnaire. We performed multiple regression and quantile regression analysis to investigate whether knee pain during each ADL was associated with physical activity. In the early group, the more knee pain they experienced while ascending stairs, the lower their physical activity was (75th regression coefficient = -1033.70, P = 0.018). In the severe group, the more knee pain they experienced while walking on a flat surface or bending to the floor or standing up, the lower their physical activity was (unstandardized coefficients = -1850.87, P = 0.026; unstandardized coefficients = -2640.35, P = 0.010). Knee pain while ascending stairs and while walking on a flat surface or bending to the floor or standing up was a probable limiting factor for physical activity in early and severe knee OA, respectively. These findings suggested that a reduction in task-specific knee pain according to disease severity could improve physical activity levels. PMID:27041381

  11. Knee pain during activities of daily living and its relationship with physical activity in patients with early and severe knee osteoarthritis.

    PubMed

    Fukutani, Naoto; Iijima, Hirotaka; Aoyama, Tomoki; Yamamoto, Yuko; Hiraoka, Masakazu; Miyanobu, Kazuyuki; Jinnouchi, Masashi; Kaneda, Eishi; Tsuboyama, Tadao; Matsuda, Shuichi

    2016-09-01

    This study aimed to investigate whether knee pain during various activities of daily living (ADLs) is associated with physical activity in patients with early and severe knee osteoarthritis (OA). We hypothesized that the painful ADLs associated with decreased physical activity differ according to disease severity. This cross-sectional study enrolled 270 patients with medial knee OA, assigned to either the early (Kellgren Lawrence [K/L] grade 1-2) or the severe group (K/L grade 3-4). Physical activity was assessed using a pedometer. Knee pain during six ADLs (waking up in the morning, walking on a flat surface, ascending stairs, etc.) was evaluated using a questionnaire. We performed multiple regression and quantile regression analysis to investigate whether knee pain during each ADL was associated with physical activity. In the early group, the more knee pain they experienced while ascending stairs, the lower their physical activity was (75th regression coefficient = -1033.70, P = 0.018). In the severe group, the more knee pain they experienced while walking on a flat surface or bending to the floor or standing up, the lower their physical activity was (unstandardized coefficients = -1850.87, P = 0.026; unstandardized coefficients = -2640.35, P = 0.010). Knee pain while ascending stairs and while walking on a flat surface or bending to the floor or standing up was a probable limiting factor for physical activity in early and severe knee OA, respectively. These findings suggested that a reduction in task-specific knee pain according to disease severity could improve physical activity levels.

  12. The coexistence of geopolymeric gel and calcium silicate hydrate at the early stage of alkaline activation

    SciTech Connect

    Yip, C.K.; Lukey, G.C.; Deventer, J.S.J. van . E-mail: jannie@unimelb.edu.au

    2005-09-01

    Scanning electron microscopy was used to study the effects of the addition of ground granulated blast furnace slag (GGBFS) on the microstructure and mechanical properties of metakaolin (MK) based geopolymers. It was found that it is possible to have geopolymeric gel and calcium silicate hydrate (CSH) gel forming simultaneously within a single binder. The coexistence of these two phases is dependent on the alkalinity of the alkali activator and the MK / GGBFS mass ratio. It has been found that the formation of CSH gel together with the geopolymeric gel occurs only in a system at low alkalinity. In the presence of high concentrations of NaOH (> 7.5 M), the geopolymeric gel is the predominant phase formed with small calcium precipitates scattered within the binder. The coexistence of the two phases is not observed unless a substantial amount of a reactive calcium source is present initially. It is thought that voids and pores within the geopolymeric binder become filled with the CSH gel. This helps to bridge the gaps between the different hydrated phases and unreacted particles; thereby resulting in the observed increase in mechanical strength for these binders.

  13. A predictive relationship between early season North Atlantic hurricane activity and the upcoming winter North Atlantic Oscillation

    NASA Astrophysics Data System (ADS)

    Boyd, Jessica; Saunders, Mark

    2016-04-01

    The winter North Atlantic Oscillation (NAO) is linked strongly to European winter climate including windstorms. Predicting the winter NAO is key to making successful seasonal predictions of European winter climate. We observe that in recent decades there are many instances of an inverse relationship between the strength of the North Atlantic hurricane season and the strength of the subsequent European winter windstorm season. Stormy European winter seasons often follow quiet Atlantic hurricane seasons and calm European winters follow active hurricane seasons. We explore the strength and temporal stability of this inverse relationship, consider a facilitating physical mechanism, and briefly discuss the implications of our findings for end users, in particular global reinsurers. We find there is a statistically significant link between North Atlantic hurricane activity and the upcoming winter NAO. The relationship is established by the midway point of the hurricane season in early September. The link is strongest when hurricane activity is in the upper or lower tercile and when summer ENSO (El Niño Southern Oscillation) is neutral. The relationship works well going back 40 years to the mid 1970s. The early winter (October-November-December) NAO is predicted best but since the early 1980s the predictive link extends to the main winter (December-January-February) NAO. The inverse link can be facilitated by a persistence and slow evolution of atmospheric circulation patterns and sea surface temperature anomalies over the North Atlantic between the summer and the winter. This persistence is best when hurricane seasons are more extreme and when summer ENSO is neutral. Our findings offer the potential for predicting the early winter and winter NAO from early September. The implied inverse relationship between US hurricane activity and European windstorm activity may enable more effective offsetting of risks between territories.

  14. Atypical Mycobacterium furunculosis occurring after pedicures.

    PubMed

    Redbord, Kelley Pagliai; Shearer, David A; Gloster, Hugh; Younger, Bruce; Connelly, Beverly L; Kindel, Susan E; Lucky, Anne W

    2006-03-01

    Mycobacterium fortuitum complex are rapidly-growing nontuberculous mycobacteria found ubiquitously in the environment including, water, soil, dust, and biofilms. M fortuitum has been reported to cause skin and soft-tissue infections in association with nail salon footbath use during pedicures. Four cases of M fortuitum complex furunculosis are reported that occurred after pedicures in the Cincinnati, Ohio/Northern Kentucky area. Dermatologists and clinicians should consider mycobacterial infections from the M fortuitum complex when patients present with nonhealing furuncles on the lower legs and should inquire about recent pedicures. Early recognition and institution of appropriate therapy are critical. Public health measures should be explored to protect against such infections, given the recent popularity of the nail care industry.

  15. Early functional magnetic resonance imaging activations predict language outcome after stroke.

    PubMed

    Saur, Dorothee; Ronneberger, Olaf; Kümmerer, Dorothee; Mader, Irina; Weiller, Cornelius; Klöppel, Stefan

    20