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Sample records for activation occurs early

  1. Age-Related Decrements in Heat Dissipation during Physical Activity Occur as Early as the Age of 40

    PubMed Central

    Larose, Joanie; Boulay, Pierre; Sigal, Ronald J.; Wright, Heather E.; Kenny, Glen P.

    2013-01-01

    Older adults typically experience greater levels of thermal strain during physical efforts in the heat compared to young individuals. While this may be related to an age-dependent reduction in whole-body sweating, no study has clearly delineated at what age this occurs. In the present study, we report direct measurements of human heat dissipation during physical activity in the heat in males ranging in age from 20–70 years. Eighty-five males performed four 15-min bouts of cycling separated by 15-min rest periods, in a calorimeter regulated to 35°C and 20% relative humidity. Direct calorimetry was used to measure total heat loss (whole-body evaporative heat loss and dry heat exchange). We also used indirect calorimetry as a continuous measure of metabolic heat production. Body heat storage was calculated as the temporal summation of heat production and total heat loss over the experimental session. Whole-body sweat rate (WBSR) was calculated from measurements of evaporative heat loss. Males were divided into five age categories for the analysis of WBSR and body heat storage: 20–31 years (n = 18), 40–44 years (n = 15), 45–49 years (n = 15), 50–55 years (n = 21) and 56–70 years (n = 16). Relative to young males, WBSR was reduced in males aged 56–70 during each exercise (all P<0.05), in males aged 50–55 during the second (P = 0.031) and third exercises (P = 0.028) and in males aged 45–49 during the final exercise bout (P = 0.046). Although not significantly different, 40–44 years old males also had a lower rate of heat loss compared to younger males. Over the sum of two hours, the change in body heat content was greater in males 40–70 years compared to young males (all P<0.05). Our findings suggest that middle-aged and older adults have impairments in heat dissipation when doing physical activity in the heat, thus possibly increasing their risk of heat-related illness under such conditions. PMID:24349447

  2. Naturally occurring changes in time spent watching television are inversely related to frequency of physical activity during early adolescence.

    PubMed

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

    2006-02-01

    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 an increase in frequency of leisure-time physical activity. That relationship was strong in magnitude and independent of sex, socioeconomic status, smoking, and the value participants placed on health, appearance, and achievement. Our results encourage the design of interventions that reduce television watching as a possible means of increasing adolescent physical activity. PMID:16338428

  3. 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…

  4. 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

  5. Oncogenic mutations in GNAQ occur early in uveal melanoma

    PubMed Central

    Onken, Michael D.; Worley, Lori A.; Long, Meghan D.; Duan, Shenghui; Council, M. Laurin; Bowcock, Anne M.; Harbour, J. William

    2008-01-01

    Purpose Early/initiating oncogenic mutations have been identified for many cancers, but such mutations remain unidentified in uveal melanoma (UM). An extensive search for such mutations was undertaken, focusing on the RAF/MEK/ERK pathway, which is often the target of initiating mutations in other types of cancer. Methods DNA samples from primary UMs were analyzed for mutations in 24 potential oncogenes that affect the RAF/MEK/ERK pathway. For GNAQ, a stimulatory αq G-protein subunit which was recently found to be mutated in uveal melanomas, re-sequencing was expanded to include 67 primary UMs and 22 peripheral blood samples. GNAQ status was analyzed for association with clinical, pathologic, chromosomal, immunohistochemical and transcriptional features. Results Activating mutations at codon 209 were identified in GNAQ in 33/67 (49%) primary UMs, including 2/9 (22%) iris melanomas and 31/58 (54%) posterior UMs. No mutations were found in the other 23 potential oncogenes. GNAQ mutations were not found in normal blood DNA samples. Consistent with GNAQ mutation being an early or initiating event, this mutation was not associated with any clinical, pathologic or molecular features associated with late tumor progression. Conclusions GNAQ mutations occur in about half of UMs, representing the most common known oncogenic mutation in this cancer. The presence of this mutation in tumors at all stages of malignant progression suggests that it is an early event in UM. Mutations in this G-protein provide new insights into UM pathogenesis and could lead to new therapeutic possibilities. PMID:18719078

  6. 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...

  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, 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...

  11. Catastrophic collapse can occur without early warning: examples of silent catastrophes in structured ecological models.

    PubMed

    Boerlijst, Maarten C; Oudman, Thomas; de Roos, André M

    2013-01-01

    Catastrophic and sudden collapses of ecosystems are sometimes preceded by early warning signals that potentially could be used to predict and prevent a forthcoming catastrophe. Universality of these early warning signals has been proposed, but no formal proof has been provided. Here, we show that in relatively simple ecological models the most commonly used early warning signals for a catastrophic collapse can be silent. We underpin the mathematical reason for this phenomenon, which involves the direction of the eigenvectors of the system. Our results demonstrate that claims on the universality of early warning signals are not correct, and that catastrophic collapses can occur without prior warning. In order to correctly predict a collapse and determine whether early warning signals precede the collapse, detailed knowledge of the mathematical structure of the approaching bifurcation is necessary. Unfortunately, such knowledge is often only obtained after the collapse has already occurred. PMID:23593506

  12. Amplification of the 20q chromosomal arm occurs early in tumorigenic transformation and may initiate cancer.

    PubMed

    Tabach, Yuval; Kogan-Sakin, Ira; 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

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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

  1. Endoscopic Submucosal Dissection for Early Gastric Neoplasia Occurring in the Remnant Stomach after Distal Gastrectomy

    PubMed Central

    Lee, Ji Young; Min, Byung-Hoon; Lee, Jung Gyu; Noh, Donghyo; Lee, Jun Haeng; Rhee, Poong-Lyul; Kim, Jae J.

    2016-01-01

    Background/Aims: Endoscopic submucosal dissection (ESD) for tumors occurring in the remnant stomach is technically difficult to perform because of limited working space and severe fibrosis and staples present around the suture line. We aimed to elucidate the feasibility and clinical outcomes of performing ESD for tumors in the remnant stomach. Methods: Between December 2007 and January 2013, 18 patients underwent ESD for tumors (six adenomas and 12 differentiated-type early gastric cancers [EGCs]) occurring in the remnant stomach after distal gastrectomy. Clinicopathologic features and clinical outcomes after ESD were retrospectively analyzed. Results: Two-thirds of the lesions were located on the body, and half were located on the suture line. En bloc resection, R0 resection, and en bloc with R0 resection rates were 88.9%, 100%, and 88.9%, respectively. Curative resection rate for EGC was 91.7%. Perforation occurred in one patient (5.6%) and was successfully managed by endoscopic closure with metallic clips and conservative management. There was no significant bleeding after ESD. During a median follow-up of 47.5 months, no local, metachronous, or extragastric recurrence was seen for either EGC or adenoma lesions. Conclusions: ESD is a feasible and effective treatment modality and can be considered a primary intervention for early gastric neoplasia occurring in the remnant stomach. PMID:26879552

  2. Nephrotic syndrome due to focal segmental glomerulosclerosis occurring in early pregnancy

    PubMed Central

    Smyth, A; Wall, C A

    2011-01-01

    Physiological proteinuria is common during pregnancy, but pathological proteinuria may also occur. Nephrotic range proteinuria most commonly occurs due to preeclampsia, but primary renal disease may also occur. We present a case of a woman who presented with nephrotic range proteinuria and nephrotic syndrome at an early stage of her second pregnancy. Due to proteinuria, haematuria, progressive symptoms and high need for medical treatment, renal biopsy was performed and she was noted to have focal segmental glomerulosclerosis (FSGS). She commenced immunosuppression but remained nephrotic during pregnancy. She delivered a healthy baby boy at 35 weeks gestation. Postpartum she remained nephrotic, and developed further complications requiring renal replacement therapy. Despite a successful pregnancy, this case of FSGS highlights that despite aggressive treatment FSGS in pregnancy is often associated with adverse renal outcome. We discuss investigations, including renal biopsy and empiric treatment options in this report.

  3. 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

  4. Potent In Vitro Antifungal Activities of Naturally Occurring Acetylenic Acids▿

    PubMed Central

    Li, Xing-Cong; Jacob, Melissa R.; Khan, Shabana I.; Ashfaq, M. Khalid; Babu, K. Suresh; Agarwal, Ameeta K.; ElSohly, Hala N.; Manly, Susan P.; Clark, Alice M.

    2008-01-01

    Our continuing effort in antifungal natural product discovery has led to the identification of five 6-acetylenic acids with chain lengths from C16 to C20: 6-hexadecynoic acid (compound 1), 6-heptadecynoic acid (compound 2), 6-octadecynoic acid (compound 3), 6-nonadecynoic acid (compound 4), and 6-icosynoic acid (compound 5) from the plant Sommera sabiceoides. Compounds 2 and 5 represent newly isolated fatty acids. The five acetylenic acids were evaluated for their in vitro antifungal activities against Candida albicans, Candida glabrata, Candida krusei, Candida tropicalis, Candida parapsilosis, Cryptococcus neoformans, Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Trichophyton mentagrophytes, and Trichophyton rubrum by comparison with the positive control drugs amphotericin B, fluconazole, ketoconazole, caspofungin, terbinafine, and undecylenic acid. The compounds showed various degrees of antifungal activity against the 21 tested strains. Compound 4 was the most active, in particular against the dermatophytes T. mentagrophytes and T. rubrum and the opportunistic pathogens C. albicans and A. fumigatus, with MICs comparable to several control drugs. Inclusion of two commercially available acetylenic acids, 9-octadecynoic acid (compound 6) and 5,8,11,14-eicosatetraynoic acid (compound 7), in the in vitro antifungal testing further demonstrated that the antifungal activities of the acetylenic acids were associated with their chain lengths and positional triple bonds. In vitro toxicity testing against mammalian cell lines indicated that compounds 1 to 5 were not toxic at concentrations up to 32 μM. Furthermore, compounds 3 and 4 did not produce obvious toxic effects in mice at a dose of 34 μmol/kg of body weight when administered intraperitoneally. Taking into account the low in vitro and in vivo toxicities and significant antifungal potencies, these 6-acetylenic acids may be excellent leads for further preclinical studies. PMID:18458131

  5. 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,…

  6. Global DNA hypomethylation occurs in the early stages of intestinal type gastric carcinoma.

    PubMed Central

    Cravo, M; Pinto, R; Fidalgo, P; Chaves, P; Glória, L; Nobre-Leitão, C; Costa Mira, F

    1996-01-01

    BACKGROUND: Global DNA hypomethylation has been found in the premalignant stages of some neoplasms and has been implicated as an important factor for tumour progression. AIMS: The aim of this study was to evaluate whether DNA hypomethylation occurs during the process of gastric carcinogenesis. METHODS: Gastric specimens were obtained from 49 patients and histologically classified as: normal 10, superficial gastritis 14, chronic atrophic gastritis with intestinal metaplasia 15, and intestinal type of gastric carcinoma 10. Global DNA methylation was assessed by incubating DNA with (3H)-S-adenosylmethionine and Sss1 methylase. A higher incorporation of (3H) methyl groups reflects a lower degree of intrinsic methylation. RESULTS: A graduated increase in (3H) methyl group incorporation into DNA was found over the range extending from normal gastric mucosa, to superficial gastritis and to chronic atrophic gastritis (136,556 (24,085) v 235,725 (38,636) v 400,998 (26,747 dpm/micrograms/DNA respectively; p = 0.0002). No further increase was found in specimens from patients with carcinoma. No differences were found between extent of DNA methylation in neoplastic or non-neoplastic mucosa from patients with gastric carcinoma. Hypomethylation of DNA increased substantially with severe atrophy (p = 0.01) or with type III intestinal metaplasia (p = 0.15). CONCLUSIONS: Global DNA hypomethylation occurs in the early stages of gastric carcinogenesis, and it may be a novel biomarker of gastric neoplasia, useful in monitoring the response to chemopreventive agents. PMID:8949650

  7. 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

  8. 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

  9. 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

  10. 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…

  11. Periods of Highly Synchronous, Non-Reentrant Endocardial Activation Cycles Occur During Long Duration Ventricular Fibrillation

    PubMed Central

    Robichaux, Robert P.; Dosdall, Derek J.; Osorio, Jose; Garner, Nicholas W.; Li, Li; Huang, Jian; Ideker, Raymond E.

    2010-01-01

    Background Little is known about long-duration ventricular fibrillation (LDVF), lasting 1-10 minutes when resuscitation is still possible. Methods and Results To determine global LV endocardial activation during LDVF, 6 canines (9.5±0.8 kg) received a 64-electrode basket catheter in the left ventricle (LV), a right ventricular (RV) catheter, and a 12-lead ECG. Activation sequences of 15 successive cycles after initiation and after 1, 2, 3, 5, 7, and 10 minutes of LDVF were determined. Early during VF, LV endocardial activation was complex and present throughout most (78.0±9.7%) of each cycle consistent with reentry. After 3-7 min of LDVF in 5 animals, endocardial activation became highly synchronized and present for only a small percentage of each cycle (18.2±7.7%), indicating that LV endocardial reentry was no longer present. During this synchronization, activations arose focally in Purkinje fibers and spread as large wavefronts to excite the Purkinje system followed by the subendocardial working myocardium. During this synchronization, the ECG continued to appear irregular, consistent with VF, and LV cycle length (183±29 ms) was significantly different than RV cycle length (144±14 ms) and significantly different than the LV cycle length when synchronization was not present (130±11 ms). Conclusion After 3-7 minutes of LDVF, a highly organized, synchronous, focal LV endocardial activation pattern frequently occurs that is not consistent with reentry but is consistent with triggered activity or abnormal automaticity in Purkinje fibers. The ECG continues to appear irregular during this period, partially because of differences in LV and RV cycle lengths. PMID:20487123

  12. Phasic motor activity reduction occurring with horizontal rapid eye movements during active sleep in human.

    PubMed

    Kohyama, J; Shimohira, M; Hasegawa, T; Kouji, T; Iwakawa, Y

    1995-01-01

    We describe the phasic reduction of motor activity occurring with horizontal rapid eye movements (REMs) during active sleep in 15 children (12 healthy children and 3 patients with severe brain damage). A REM-related decrease in intercostal muscle activity was demonstrated by averaging integrated surface electromyograms. In the healthy subjects, this reduction had a mean latency from the REM onset of 37.1 ms and a duration of 225.9 ms. This phenomenon was also observed in the 3 patients who had lost cerebral function. We hypothesized a brainstem origin for the effect. A REM-related mentalis muscle activity loss, detected by averaging mentalis muscle twitches, was observed in 10 healthy children among the subjects. This loss began at 59.1 ms before the onset of REMs and lasted for 230.2 ms on average. In addition, a transient decrease in integrated REM activity surrounding mentalis muscle twitches (a twitch-related reduction of REMs) was observed. We discuss the similarity between REM-related phasic reduction of muscle activity obtained for intercostal and mentalis muscles and pontogeniculo-occipital (PGO) wave-related inhibitory postsynaptic potentials reported for feline lumbar and trigeminal motoneurons, respectively. We then assume the presence of a phasic event generator, functioning during active sleep in healthy humans, which triggers at least three generators; that is, the generator of PGO waves (or REMs), motor inhibition, and of motor excitation including muscle twitches. PMID:8751071

  13. A novel naturally occurring tandem promoter in modified vaccinia virus ankara drives very early gene expression and potent immune responses.

    PubMed

    Wennier, Sonia T; Brinkmann, Kay; Steinhäußer, Charlotte; Mayländer, Nicole; Mnich, Claudia; Wielert, Ursula; Dirmeier, Ulrike; Hausmann, Jürgen; Chaplin, Paul; Steigerwald, Robin

    2013-01-01

    Modified vaccinia virus Ankara (MVA) has been shown to be suitable for the generation of experimental vaccines against cancer and infectious diseases, eliciting strong humoral and cellular immune responses. In viral vectored vaccines, strong recombinant antigen expression and timing of expression influence the quantity and quality of the immune response. Screening of synthetic and native poxvirus promoters for strong protein expression in vitro and potent immune responses in vivo led to the identification of the MVA13.5L promoter, a unique and novel naturally occurring tandem promoter in MVA composed of two 44 nucleotide long repeated motifs, each containing an early promoter element. The MVA13.5L gene is highly conserved across orthopoxviruses, yet its function is unknown. The unique structure of its promoter is not found for any other gene in the MVA genome and is also conserved in other orthopoxviruses. Comparison of the MVA13.5L promoter activity with synthetic poxviral promoters revealed that the MVA13.5L promoter produced higher levels of protein early during infection in HeLa cells and particularly in MDBK cells, a cell line in which MVA replication stops at an early stage before the expression of late genes. Finally, a recombinant antigen expressed under the control of this novel promoter induced high antibody titers and increased CD8 T cell responses in homologous prime-boost immunization compared to commonly used promoters. In particular, the recombinant antigen specific CD8 T cell responses dominated over the immunodominant B8R vector-specific responses after three vaccinations and even more during the memory phase. These results have identified the native MVA13.5L promoter as a new potent promoter for use in MVA vectored preventive and therapeutic vaccines. PMID:23951355

  14. A Novel Naturally Occurring Tandem Promoter in Modified Vaccinia Virus Ankara Drives Very Early Gene Expression and Potent Immune Responses

    PubMed Central

    Wennier, Sonia T.; Brinkmann, Kay; Steinhäußer, Charlotte; Mayländer, Nicole; Mnich, Claudia; Wielert, Ursula; Dirmeier, Ulrike; Hausmann, Jürgen; Chaplin, Paul; Steigerwald, Robin

    2013-01-01

    Modified vaccinia virus Ankara (MVA) has been shown to be suitable for the generation of experimental vaccines against cancer and infectious diseases, eliciting strong humoral and cellular immune responses. In viral vectored vaccines, strong recombinant antigen expression and timing of expression influence the quantity and quality of the immune response. Screening of synthetic and native poxvirus promoters for strong protein expression in vitro and potent immune responses in vivo led to the identification of the MVA13.5L promoter, a unique and novel naturally occurring tandem promoter in MVA composed of two 44 nucleotide long repeated motifs, each containing an early promoter element. The MVA13.5L gene is highly conserved across orthopoxviruses, yet its function is unknown. The unique structure of its promoter is not found for any other gene in the MVA genome and is also conserved in other orthopoxviruses. Comparison of the MVA13.5L promoter activity with synthetic poxviral promoters revealed that the MVA13.5L promoter produced higher levels of protein early during infection in HeLa cells and particularly in MDBK cells, a cell line in which MVA replication stops at an early stage before the expression of late genes. Finally, a recombinant antigen expressed under the control of this novel promoter induced high antibody titers and increased CD8 T cell responses in homologous prime-boost immunization compared to commonly used promoters. In particular, the recombinant antigen specific CD8 T cell responses dominated over the immunodominant B8R vector-specific responses after three vaccinations and even more during the memory phase. These results have identified the native MVA13.5L promoter as a new potent promoter for use in MVA vectored preventive and therapeutic vaccines. PMID:23951355

  15. Retinoid-induced apoptosis and Sp1 cleavage occur independently of transcription and require caspase activation.

    PubMed Central

    Piedrafita, F J; Pfahl, M

    1997-01-01

    Vitamin A and its derivatives, the retinoids, are essential regulators of many important biological functions, including cell growth and differentiation, development, homeostasis, and carcinogenesis. Natural retinoids such as all-trans retinoic acid can induce cell differentiation and inhibit growth of certain cancer cells. We recently identified a novel class of synthetic retinoids with strong anti-cancer cell activities in vitro and in vivo which can induce apoptosis in several cancer cell lines. Using an electrophoretic mobility shift assay, we analyzed the DNA binding activity of several transcription factors in T cells treated with apoptotic retinoids. We found that the DNA binding activity of the general transcription factor Sp1 is lost in retinoid-treated T cells undergoing apoptosis. A truncated Sp1 protein is detected by immunoblot analysis, and cytosolic protein extracts prepared from apoptotic cells contain a protease activity which specifically cleaves purified Sp1 in vitro. This proteolysis of Sp1 can be inhibited by N-ethylmaleimide and iodoacetamide, indicating that a cysteine protease mediates cleavage of Sp1. Furthermore, inhibition of Sp1 cleavage by ZVAD-fmk and ZDEVD-fmk suggests that caspases are directly involved in this event. In fact, caspases 2 and 3 are activated in T cells after treatment with apoptotic retinoids. The peptide inhibitors also blocked retinoid-induced apoptosis, as well as processing of caspases and proteolysis of Sp1 and poly(ADP-ribose) polymerase in intact cells. Degradation of Sp1 occurs early during apoptosis and is therefore likely to have profound effects on the basal transcription status of the cell. Interestingly, retinoid-induced apoptosis does not require de novo mRNA and protein synthesis, suggesting that a novel mechanism of retinoid signaling is involved, triggering cell death in a transcriptional activation-independent, caspase-dependent manner. PMID:9343396

  16. Co-Occurring Problems of Early Onset Persistent, Childhood Limited, and Adolescent Onset Conduct Problem Youth

    ERIC Educational Resources Information Center

    Barker, Edward D.; Oliver, Bonamy R.; Maughan, Barbara

    2010-01-01

    Background: It is increasingly recognized that youth who follow early onset persistent (EOP), childhood limited (CL) and adolescent onset (AO) trajectories of conduct problems show somewhat varying patterns of risk (in childhood) and adjustment problems (in adolescence and adulthood). Little, however, is known about how other adjustment problems…

  17. 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

  18. Synaptic activation of ribosomal protein S6 phosphorylation occurs locally in activated dendritic domains.

    PubMed

    Pirbhoy, Patricia Salgado; Farris, Shannon; Steward, Oswald

    2016-06-01

    Previous studies have shown that induction of long-term potentiation (LTP) induces phosphorylation of ribosomal protein S6 (rpS6) in postsynaptic neurons, but the functional significance of rpS6 phosphorylation is poorly understood. Here, we show that synaptic stimulation that induces perforant path LTP triggers phosphorylation of rpS6 (p-rpS6) locally near active synapses. Using antibodies specific for phosphorylation at different sites (ser235/236 versus ser240/244), we show that strong synaptic activation led to dramatic increases in immunostaining throughout postsynaptic neurons with selectively higher staining for p-ser235/236 in the activated dendritic lamina. Following LTP induction, phosphorylation at ser235/236 was detectable by 5 min, peaked at 30 min, and was maintained for hours. Phosphorylation at both sites was completely blocked by local infusion of the NMDA receptor antagonist, APV. Despite robust induction of p-rpS6 following high frequency stimulation, assessment of protein synthesis by autoradiography revealed no detectable increases. Exploration of a novel environment led to increases in the number of p-rpS6-positive neurons throughout the forebrain in a pattern reminiscent of immediate early gene induction and many individual neurons that were p-rpS6-positive coexpressed Arc protein. Our results constrain hypotheses about the possible role of rpS6 phosphorylation in regulating postsynaptic protein synthesis during induction of synaptic plasticity. PMID:27194793

  19. Development sites and early stages of eleven species of Clusiidae (Diptera) occurring in Europe.

    PubMed

    Rotheray, Graham E; Horsfield, David

    2013-01-01

    Two hundred and ninety-six rearing records of 11 clusiid species (Diptera, Clusiidae) were obtained from 8 tree species in England, Finland, France, Norway, Russia and Scotland, mainly during the period 1994 to 2004. Larvae and puparia were found between annual layers of whitewood (sapwood and heartwood) of wet, decay-softened, dead wood. Levels of host tree specificity were low, most species were reared from 2-4 host trees, maximum 6. The clusiid larva is distinguished by: a small, translucent head skeleton with an obliquely-shaped apex to the artium; a pseudocephalon fixed in an inverted position except for an external, flattened section bearing the antennomaxillary organs; a spherical prothorax with a truncate rim embedded with sensilla and, a wedge-shaped anal segment bearing a pair of conspicuous, sclerotised, red-brown hooks on the inner margins of which are the posterior spiracular plates. Many of these features support a distinctive feeding mechanism, spot-sucking of biofilm coating wet, decaying whitewood. Early stage characters support the results of recent supraspecific taxonomic and systematic investigations, such as the synonymy of Paraclusia Czerny under Clusia Haliday and the recognition of species groups in Clusiodes Coquillett. Based on early stages, supraspecific clusiid taxa are easily recognised but at species level, differences are relatively fine-grained and minor. A key is provided to identify puparia of species reared in this study. PMID:26131483

  20. Changes in Vascular Tone Occur Early During Hemodialysis Treatments Independently of Volume Reduction.

    PubMed

    Power, Albert; Charitaki, Evangelia; Davenport, Andrew

    2016-07-01

    Hypotension commonly occurs during hemodialysis (HD). Hypotension can result from an absolute reduction in plasma volume following excessive ultrafiltration or from a reduction in vascular tone. We hypothesized that changes in vascular tone could occur during dialysis. Aortic pulse wave velocity (aPWV) was measured in 197 HD patients, mean age 63.3 ± 16.6 years, 62% male, 49% diabetic, during a single HD session. aPWV did not change (9.6 ± 2.2 vs. 9.6 ± 2.2 m/s) with HD. Systolic blood pressure (SBP) declined from 151 ± 31 to 147 ± 32 after 20 min and to 140 ± 36 mm Hg on completion of HD (P < 0.05), with an ultrafiltration volume of 2.2 ± 0.9 L over a 3.9 ± 0.4 h HD session. Aortic SBP declined from 154 ± 32 to 146 ± 29 after 20 min and 143 ± 35 at the end of HD, P < 0.001. Aortic augmentation index (Aortic Aix) decreased from 65% (52-79%) to 36.7% (23.3-52.9%) by 20 min and to 34.3 (15.1-49.1%) on completion of HD (P < 0.05), and brachial augmentation index (brachial Aix) from 5.7% (-25.2 to 27.5%) to -1.9% (-2.2 to 30.1%) and -6.6% (-44 to 22.7%), respectively, P < 0.05. Diastolic reflection area (DRA) increased from 36.7 (27.9-46.3) to 40.4 (32.2-51) after 20 min and 47.1 (34.2-60.5) on completion of HD, P < 0.05. We report changes in arterial tone within 20 min of starting HD, when minimal ultrafiltration has occurred, suggesting that volume changes may not be the only predisposing cause of intradialytic hypotension. The combination of a fall in SBP and a rise in DRA would suggest a reduction in coronary blood flow in keeping with reports of "myocardial stunning" during HD. PMID:26496182

  1. Neuroplastic changes occur early in the development of pancreatic ductal adenocarcinoma

    PubMed Central

    Stopczynski, Rachelle E.; Normolle, Daniel P.; Hartman, Douglas J.; Ying, Haoqiang; DeBerry, Jennifer J.; Bielefeldt, Klaus; Rhim, Andrew D.; DePinho, Ronald A.; Albers, Kathryn M.; Davis, Brian M.

    2014-01-01

    Perineural tumor invasion of intrapancreatic nerves, neurogenic inflammation, and tumor metastases along extrapancreatic nerves are key features of pancreatic malignancies. Animal studies show that chronic pancreatic inflammation produces hypertrophy and hypersensitivity of pancreatic afferents and that sensory fibers may themselves drive inflammation via neurogenic mechanisms. Whereas genetic mutations are required for cancer development, inflammation has been shown to be a precipitating event that can accelerate the transition of precancerous lesions to cancer. These observations led us to hypothesize that inflammation that accompanies early phases of PDAC would produce pathologic changes in pancreatic neurons and innervation. Using a lineage labeled genetically engineered mouse model of PDAC we found that pancreatic neurotrophic factor mRNA expression and sensory innervation increased dramatically when only pancreatic intraepithelial neoplasia (PanIN) were apparent. These changes correlated with pain-related decreases in exploratory behavior and increased expression of nociceptive genes in sensory ganglia. At later stages, cells of pancreatic origin could be found in the celiac and sensory ganglia along with metastases to the spinal cord. These results demonstrate that the nervous system participates in all stages of PDAC, including those that precede appearance of cancer. PMID:24448244

  2. 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

  3. Early skin testing is effective for diagnosis of hypersensitivity reactions occurring during anesthesia.

    PubMed

    Lafuente, A; Javaloyes, G; Berroa, F; Goikoetxea, M J; Moncada, R; Núñez-Córdoba, J M; Cabrera-Freitag, P; D'Amelio, C; Sanz, M L; Gastaminza, G

    2013-06-01

    Allergic skin tests have to be performed 4-6 weeks after an allergic anesthetic reaction. Patients with allergic reactions during anesthesia were prospectively included (n = 44). Skin tests were performed in two stages: (i) Stage 1 (S1), 0-4 days after the reaction; and (ii) Stage 2 (S2), 4-8 weeks after. Five (11.5%) surgical procedures were suspended due to the reaction. Positive skin tests were obtained in 25/44 patients (57%). Allergic diagnosis was carried out at S1 in 15/25 (60%) and at S2 in 10/25 (40%). Three patients resulted positive only in S1. Overall agreement among S1 and S2 skin tests was 70.45%. The kappa statistic was 0.41 (P-value = 0.002). Odds ratio of obtaining a false negative in S1 (compared with S2) was 3.33. Early allergological study is useful, could minimize false negatives, but should be considered as a complement to late skin tests. PMID:23646901

  4. Antibacterial Activities of Naturally occurring Compounds against Mycobacterium avium subspecies paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antibacterial activities of 19 naturally-occurring compounds (including essential oils and some of their isolated constituents, apple and green tea polyphenols and other plant extracts) against three strains of Mycobacterium avium subspecies paratuberculosis (Map), a bovine isolate NCTC 8578, a raw ...

  5. Conduct problems, depressive symptomatology and their co-occurring presentation in childhood as predictors of adjustment in early adolescence.

    PubMed

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

    2006-10-01

    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. 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…

  7. Co-occurring Anxiety Influences Patterns of Brain Activity in Depression

    PubMed Central

    Engels, Anna S.; Heller, Wendy; Spielberg, Jeffrey M.; Warren, Stacie L.; Sutton, Bradley P.; Banich, Marie T.; Miller, Gregory A.

    2011-01-01

    Brain activation associated with anhedonic depression and co-occurring anxious arousal and anxious apprehension was measured by fMRI during performance of an emotion-word Stroop task. Consistent with EEG findings, depression was associated with rightward frontal lateralization in dorsolateral prefrontal cortex (DLPFC), but only when anxious arousal was elevated and anxious apprehension was low. Activity in right inferior frontal gyrus (IFG) was also reduced for depression under the same conditions. In contrast, depression was associated with more activity in anterior cingulate cortex (dACC and rACC) and bilateral amygdala. Results imply that depression, particularly when accompanied by anxious arousal, may result in a failure to implement top-down processing by appropriate brain regions (left DLPFC, right IFG) due to increased activation in regions associated with responding to emotionally salient information (right DLPFC, amygdala). PMID:20233962

  8. Pressure oscillations occurring in a centrifugal compressor system with and without passive and active surge control

    SciTech Connect

    Jungowski, W.M.; Weiss, M.H.; Price, G.R.

    1996-01-01

    A study of pressure oscillations occurring in small centrifugal compressor systems without a plenum is presented. Active and passive surge control were investigated theoretically and experimentally for systems with various inlet and discharge piping configurations. The determination of static and dynamic stability criteria was based on Greitzer`s (1981) lumped parameter model modified to accommodate capacitance of the piping. Experimentally, passive control using globe valves closely coupled to the compressor prevented the occurrence of surge even with the flow reduced to zero. Active control with a sleeve valve located at the compressor was effective but involved a significant component of passive throttling which reduced the compressor efficiency. With an oscillator connected to a short side branch at the compressor, effective active control was achieved without throttling. Both methods of active control reduced the flow rate at surge onset by about 30%. In general, the experiments qualitatively confirmed the derived stability criteria.

  9. 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

  10. Poly(anhydride-esters) comprised exclusively of naturally occurring antimicrobials and EDTA: antioxidant and antibacterial activities.

    PubMed

    Carbone-Howell, Ashley L; Stebbins, Nicholas D; Uhrich, Kathryn E

    2014-05-12

    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. Oxytocin neuron activation prevents hypertension that occurs with chronic intermittent hypoxia/hypercapnia in rats.

    PubMed

    Jameson, Heather; Bateman, Ryan; Byrne, Peter; Dyavanapalli, Jhansi; Wang, Xin; Jain, Vivek; Mendelowitz, David

    2016-06-01

    Hypertension is a common outcome associated with obstructive sleep apnea (OSA), a prevalent yet poorly treated cardiovascular disease. Recent studies showed oxytocin (OXT), released from hypothalamic paraventricular nucleus (PVN) neurons, activates cardiac vagal neurons in the dorsal motor nucleus of the vagus (DMNX) and may blunt cardiovascular responses to stress. This study tests whether the release of OXT from PVN fibers in the DMNX is diminished with chronic intermittent hypoxia-hypercapnia (CIH/H) exposure, an animal model of OSA, and whether activation of PVN OXT neurons restores OXT release in the DMNX and prevents the hypertension resulting from CIH/H. To assess OXT release from PVN fibers, Chinese hamster ovarian (CHO) cells were engineered to be highly sensitive to OXT by stable expression of the human recombinant OXT receptor and the calcium indicator R-GECO1. PVN fibers in the DMNX were selectively photoactivated in vitro by expression of channelrhodopsin. The release of OXT onto CHO cells in the DMNX was blunted in rats exposed to 21 days of CIH/H. Chronic activation of PVN OXT neurons in vivo, using designer receptors exclusively activated by designer drugs, restored the release of OXT onto CHO cells in the DMNX. Chronic PVN OXT neuron activation in vivo also prevented the hypertension that occurred in conscious unrestrained telemetry-equipped sham rats exposed to 3 wk of CIH/H. These results demonstrate that chronic activation of OXT neurons restores the release of OXT from PVN fibers in the DMNX and prevents the hypertension that occurs with 3 wk of CIH/H exposure. PMID:27016581

  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. Acetic acid suppresses the increase in disaccharidase activity that occurs during culture of caco-2 cells.

    PubMed

    Ogawa, N; Satsu, H; Watanabe, H; Fukaya, M; Tsukamoto, Y; Miyamoto, Y; Shimizu, M

    2000-03-01

    To understand how blood glucose level is lowered by oral administration of vinegar, we examined effects of acetic acid on glucose transport and disaccharidase activity in Caco-2 cells. Cells were cultured for 15 d in a medium containing 5 mmol/L of acetic acid. This chronic treatment did not affect cell growth or viability, and furthermore, apoptotic cell death was not observed. Glucose transport, evaluated with a nonmetabolizable substrate, 3-O-methyl glucose, also was not affected. However, the increase of sucrase activity observed in control cells (no acetic acid) was significantly suppressed by acetic acid (P < 0.01). Acetic acid suppressed sucrase activity in concentration- and time-dependent manners. Similar treatments (5 mmol/L and 15 d) with other organic acids such as citric, succinic, L-maric, L-lactic, L-tartaric and itaconic acids, did not suppress the increase in sucrase activity. Acetic acid treatment (5 mmol/L and 15 d) significantly decreased the activities of disaccharidases (sucrase, maltase, trehalase and lactase) and angiotensin-I-converting enzyme, whereas the activities of other hydrolases (alkaline phosphatase, aminopeptidase-N, dipeptidylpeptidase-IV and gamma-glutamyltranspeptidase) were not affected. To understand mechanisms underlying the suppression of disaccharidase activity by acetic acid, Northern and Western analyses of the sucrase-isomaltase complex were performed. Acetic acid did not affect the de novo synthesis of this complex at either the transcriptional or translational levels. The antihyperglycemic effect of acetic acid may be partially due to the suppression of disaccharidase activity. This suppression seems to occur during the post-translational processing. PMID:10702577

  15. Naturally occurring amino acid derivatives with herbicidal, fungicidal or insecticidal activity.

    PubMed

    Lamberth, Clemens

    2016-04-01

    Several naturally occurring amino acid derivatives display significant activities against weeds, fungi and insects: some of them have been even commercialized and are applied as crop protection agents. The 53 most important amino acid natural products with such efficacy are presented in this review together with their natural source, mode of action and biological activity. The diversity of the manifold bacterial, fungal and plantal sources of these compounds is impressive as well as their completely different structural scaffolds, ranging from cyclopeptides via unique non-proteinogenic amino acids to peptidyl nucleosides, the broad range of target enzymes from several different biochemical pathways, which they inhibit and also the plethora of different weeds, fungi and insects they are able to control. PMID:26801938

  16. Acetaminophen-Induced Hepatotoxicity in Mice Occurs with Inhibition of Activity and Nitration of Mitochondrial Manganese Superoxide Dismutase

    PubMed Central

    Agarwal, Rakhee; MacMillan-Crow, Lee Ann; Rafferty, Tonya M.; Saba, Hamida; Roberts, Dean W.; Fifer, E. Kim; James, Laura P.

    2011-01-01

    In overdose the analgesic/antipyretic acetaminophen (APAP) is hepatotoxic. Toxicity is mediated by initial hepatic metabolism to N-acetyl-p-benzoquinone imine (NAPQI). After low doses NAPQI is efficiently detoxified by GSH. However, in overdose GSH is depleted, NAPQI covalently binds to proteins as APAP adducts, and oxygen/nitrogen stress occurs. Toxicity is believed to occur by mitochondrial dysfunction. Manganese superoxide dismutase (MnSOD) inactivation by protein nitration has been reported to occur during other oxidant stress-mediated diseases. MnSOD is a critical mitochondrial antioxidant enzyme that prevents peroxynitrite formation within the mitochondria. To examine the role of MnSOD in APAP toxicity, mice were treated with 300 mg/kg APAP. GSH was significantly reduced by 65% at 0.5 h and remained reduced from 1 to 4 h. Serum alanine aminotransferase did not significantly increase until 4 h and was 2290 IU/liter at 6 h. MnSOD activity was significantly reduced by 50% at 1 and 2 h. At 1 h, GSH was significantly depleted by 62 and 80% at nontoxic doses of 50 and 100 mg/kg, respectively. No further GSH depletion occurred with hepatotoxic doses of 200 and 300 mg/kg APAP. A dose response decrease in MnSOD activity was observed for APAP at 100, 200, and 300 mg/kg. Immunoprecipitation of MnSOD from livers of APAP-treated mice followed by Western blot analysis revealed nitrated MnSOD. APAP-MnSOD adducts were not detected. Treatment of recombinant MnSOD with NAPQI did not produce APAP protein adducts. The data indicate that MnSOD inactivation by nitration is an early event in APAP-induced hepatic toxicity. PMID:21205919

  17. 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. PMID:18785051

  18. Telomerase Activity is Downregulated Early During Human Brain Development.

    PubMed

    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

  19. 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

  20. 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

  1. Selenium compounds activate early barriers of tumorigenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Selenium chemoprevention by apoptosis has been well studied, but it is not clear whether selenium can activate early barriers of tumorigenesis, namely senescence and DNA damage response. To address this issue, we treated normal and cancerous cells with a gradient concentration of sodium selenite, me...

  2. 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. PMID:24091232

  3. 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

  4. 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

  5. Abnormal neuronal patterning occurs during early postnatal brain development of Scn1b-null mice and precedes hyperexcitability.

    PubMed

    Brackenbury, William J; Yuan, Yukun; O'Malley, Heather A; Parent, Jack M; Isom, Lori L

    2013-01-15

    Voltage-gated Na(+) channel (VGSC) β1 subunits, encoded by SCN1B, are multifunctional channel modulators and cell adhesion molecules (CAMs). Mutations in SCN1B are associated with the genetic epilepsy with febrile seizures plus (GEFS+) spectrum disorders in humans, and Scn1b-null mice display severe spontaneous seizures and ataxia from postnatal day (P)10. The goal of this study was to determine changes in neuronal pathfinding during early postnatal brain development of Scn1b-null mice to test the hypothesis that these CAM-mediated roles of Scn1b may contribute to the development of hyperexcitability. c-Fos, a protein induced in response to seizure activity, was up-regulated in the Scn1b-null brain at P16 but not at P5. Consistent with this, epileptiform activity was observed in hippocampal and cortical slices prepared from the P16 but not from the P5-P7 Scn1b-null brain. On the basis of these results, we investigated neuronal pathfinding at P5. We observed disrupted fasciculation of parallel fibers in the P5 null cerebellum. Further, P5 null mice showed reduced neuron density in the dentate gyrus granule cell layer, increased proliferation of granule cell precursors in the hilus, and defective axonal extension and misorientation of somata and processes of inhibitory neurons in the dentate gyrus and CA1. Thus, Scn1b is critical for neuronal proliferation, migration, and pathfinding during the critical postnatal period of brain development. We propose that defective neuronal proliferation, migration, and pathfinding in response to Scn1b deletion may contribute to the development of hyperexcitability. PMID:23277545

  6. Bi-site activation occurs with the native and nucleotide-depleted mitochondrial F1-ATPase.

    PubMed Central

    Milgrom, Y M; Murataliev, M B; Boyer, P D

    1998-01-01

    Experiments are reported on the uni-site catalysis and the transition from uni-site to multi-site catalysis with bovine heart mitochondrial F1-ATPase. The very slow uni-site ATP hydrolysis is shown to occur without tightly bound nucleotides present and with or without Pi in the buffer. Measurements of the transition to higher rates and the amount of bound ATP committed to hydrolysis as the ATP concentration is increased at different fixed enzyme concentrations give evidence that the filling of a second site can initiate near maximal turnover rates. They provide rate constant information, and show that an apparent Km for a second site of about 2 microM and Vmax of 10 s-1, as suggested by others, is not operative. Careful initial velocity measurements also eliminate other suggested Km values and are consistent with bi-site activation to near maximal hydrolysis rates, with a Km of about 130 microM and Vmax of about 700 s-1. However, the results do not eliminate the possibility of additional 'hidden' Km values with similar Vmax:Km ratios. Recent data on competition between TNP-ATP and ATP revealed a third catalytic site for ATP in the millimolar concentration range. This result, and those reported in the present paper, allow the conclusion that the mitochondrial F1-ATPase can attain near maximal activity in bi-site catalysis. Our data also add to the evidence that a recent claim, that the mitochondrial F1-ATPase does not show catalytic site cooperativity, is invalid. PMID:9480927

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

    PubMed Central

    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

    2015-01-01

    In Krabbe’s Disease (KD), a leukodystrophy caused by β-galactosylceramidase deficiency, demyelination and a myelin-independent axonopathy contribute 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 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 timepoint 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, open new windows of action to effectively correct the neuropathology that characterizes this disorder. PMID:24607884

  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. PMID:26814015

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

    ERIC Educational Resources Information Center

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

    2006-01-01

    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…

  11. 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…

  12. Family Intervention Effects on Co-Occurring Early Childhood Behavioral and Emotional Problems: A Latent Transition Analysis Approach

    ERIC Educational Resources Information Center

    Connell, Arin; Bullock, Bernadette Marie; Dishion, Thomas J.; Shaw, Daniel; Wilson, Melvin; Gardner, Frances

    2008-01-01

    This study used latent transition analysis (LTA) to examine changes in early emotional and behavioral problems in children age 2 to 4 years resulting from participation in a family-centered intervention. A sample of 731 economically disadvantaged families was recruited from among participants in a national food supplement and nutrition program.…

  13. 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.

  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. 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

  16. 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

  17. Peak tornado activity is occurring earlier in the heart of "Tornado Alley"

    NASA Astrophysics Data System (ADS)

    Long, John A.; Stoy, Paul C.

    2014-09-01

    Tornado frequency may increase as the factors that contribute to severe convection are altered by a changing climate. Attributing changes in tornado frequency to observed global climate change is complicated because observational effort has increased over time, but studies of the seasonal distribution of tornado activity may avoid sampling biases. We demonstrate that peak tornado activity has shifted 7 days earlier in the year over the past six decades in the central and southern US Great Plains, the area with the highest global incidence of tornado activity. Results are largely unrelated to large-scale climate oscillations, and observed climate trends cannot fully account for observations, which suggest that changes to regional climate dynamics should be further investigated. Tornado preparedness efforts at individual to national levels should be cognizant of the trend toward earlier peak tornado activity across the heart of "Tornado Alley".

  18. The antifibrotic effects of plasminogen activation occur via prostaglandin E2 synthesis in humans and mice

    PubMed Central

    Bauman, Kristy A.; Wettlaufer, Scott H.; Okunishi, Katsuhide; Vannella, Kevin M.; Stoolman, Joshua S.; Huang, Steven K.; Courey, Anthony J.; White, Eric S.; Hogaboam, Cory M.; Simon, Richard H.; Toews, Galen B.; Sisson, Thomas H.; Moore, Bethany B.; Peters-Golden, Marc

    2010-01-01

    Plasminogen activation to plasmin protects from lung fibrosis, but the mechanism underlying this antifibrotic effect remains unclear. We found that mice lacking plasminogen activation inhibitor–1 (PAI-1), which are protected from bleomycin-induced pulmonary fibrosis, exhibit lung overproduction of the antifibrotic lipid mediator prostaglandin E2 (PGE2). Plasminogen activation upregulated PGE2 synthesis in alveolar epithelial cells, lung fibroblasts, and lung fibrocytes from saline- and bleomycin-treated mice, as well as in normal fetal and adult primary human lung fibroblasts. This response was exaggerated in cells from Pai1–/– mice. Although enhanced PGE2 formation required the generation of plasmin, it was independent of proteinase-activated receptor 1 (PAR-1) and instead reflected proteolytic activation and release of HGF with subsequent induction of COX-2. That the HGF/COX-2/PGE2 axis mediates in vivo protection from fibrosis in Pai1–/– mice was demonstrated by experiments showing that a selective inhibitor of the HGF receptor c-Met increased lung collagen to WT levels while reducing COX-2 protein and PGE2 levels. Of clinical interest, fibroblasts from patients with idiopathic pulmonary fibrosis were found to be defective in their ability to induce COX-2 and, therefore, unable to upregulate PGE2 synthesis in response to plasmin or HGF. These studies demonstrate crosstalk between plasminogen activation and PGE2 generation in the lung and provide a mechanism for the well-known antifibrotic actions of the fibrinolytic pathway. PMID:20501949

  19. 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

  20. 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.

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

    SciTech Connect

    Binet, Francois; 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 eIF2{alpha} 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.

  2. 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.

  3. 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.

  4. 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.

    2016-04-01

    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.

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

    PubMed Central

    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

  6. 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

  7. Aluminum-chloride-phthalocyanine encapsulated in liposomes: activity against naturally occurring dog breast cancer cells.

    PubMed

    Rocha, Martha S T; Lucci, Carolina M; Longo, João Paulo F; Galera, Paula D; Simioni, Andreza R; Lacava, Zulmira G M; Tedesco, Antônio C; Azevedo, Ricardo B

    2012-04-01

    Breast tumors represent the most common malignant tumors. Current treatments for humans and pets rely on tumor excision and adjuvant chemotherapy, which may affect both cancer cells and normal cells. Photodynamic therapy (PDT) is an approved treatment modality for a variety of cancers and was recently recommended as a first-line treatment for non-melanoma skin cancers for humans. The main purpose of the present study was to determine the efficacy of PDT using aluminum-chloride-phthalocyanine that is encapsulated in liposomes and LED as a light source to kill naturally occurring female dog breast cancer in vitro. The cytotoxicity behavior of the encapsulated photosensitizer in the dark and under irradiation using the 670 nm laser were investigated using classical trypan blue and MTT cell viability tests, acridine orange and ethidium bromide staining to label organelles, and cell morphology. Cell morphology was evaluated using light and electron microscopy. Our results demonstrate a reduced cell viability that is associated with morphologic alterations. The neoplasic cell destruction was predominantly mediated via a necrotic process, which was assayed using acridine orange and ethidium bromide staining. These findings were confirmed using light and electronic microscopy. The photosensitizer or laser irradiation alone did not induce cytotoxicity or morphological alterations, indicating the safety and efficacy of PDT with chloro-aluminum-phthalocyanine that was encapsulated in liposomes for the treatment of breast cancer cells in vitro. PMID:22515076

  8. 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.

  9. Agonist-activated Ca2+ influx occurs at stable plasma membrane and endoplasmic reticulum junctions

    PubMed Central

    Treves, Susan; Vukcevic, Mirko; Griesser, Johanna; Armstrong, Clara-Franzini; Zhu, Michael X.; Zorzato, Fancesco

    2010-01-01

    Junctate is a 33 kDa integral protein of sarco(endo)plasmic reticulum membranes that forms a macromolecular complex with inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] receptors and TRPC3 channels. TIRF microscopy shows that junctate enhances the number of fluorescent puncta on the plasma membrane. The size and distribution of these puncta are not affected by the addition of agonists that mobilize Ca2+ from Ins(1,4,5)P3-sensitive stores. Puncta are associated with a significantly larger number of peripheral junctions between endoplasmic reticulum and plasma membrane, which are further enhanced upon stable co-expression of junctate and TRPC3. The gap between the membranes of peripheral junctions is bridged by regularly spaced electron-dense structures of 10 nm. Ins(1,4,5)P3 inhibits the interaction of the cytoplasmic N-terminus of junctate with the ligand-binding domain of the Ins(1,4,5)P3 receptor. Furthermore, Ca2+ influx evoked by activation of Ins(1,4,5)P3 receptors is increased where puncta are located. We conclude that stable peripheral junctions between the plasma membrane and endoplasmic reticulum are the anatomical sites of agonist-activated Ca2+ entry. PMID:21062895

  10. Tryptophan depletion in depressed patients occurs independent of kynurenine pathway activation.

    PubMed

    Hughes, Martina M; Carballedo, Angela; McLoughlin, Declan M; Amico, Francesco; Harkin, Andrew; Frodl, Thomas; Connor, Thomas J

    2012-08-01

    The kynurenine pathway (KP) and its rate-limiting tryptophan degrading enzyme indolamine 2,3-dioxygenase (IDO) have been implicated in the pathogenesis of depression. IDO expression is driven by inflammatory cytokines, and has been suggested as the link between inflammation and a serotonergic deficit in depression. Studies also indicate that inflammatory cytokines upregulate the serotonin transporter (SERT), representing another mechanism by which inflammation could influence serotonin availability. Here we examined circulating concentrations of inflammatory cytokines (IFN-γ, TNF-α, IL-1β, IL-6), and the acute phase protein CRP alongside plasma tryptophan, kynurenine, kynurenic acid (KYNA) and 3-hydroxyanthranilic acid (3-HAA) concentrations, and whole blood mRNA expression of IDO, kynurenine aminotransferases (KAT I and II), kynurenine-3-monooxygenase (KMO), kynureninase and SERT in patients with major depressive disorder (MDD) compared with age and sex-matched controls. Whilst no changes in TNF-α or IL-1β were observed, plasma concentrations of IL-6, IFN-γ and CRP were increased in the depressed cohort. Despite this inflammatory phenotype, IDO expression or plasma kynurenine were not significantly different between MDD patients and controls. In addition, there was no difference between controls and depressives in concentrations of KYNA and 3-HAA, or in expression of enzymes KAT, KMO or kynureninase that drive their production. Nonetheless, a depletion in tryptophan was evident in depressed patients and was correlated with HAM-D scores. In addition, we failed to observe any difference in SERT mRNA expression in the blood cells from patients with MDD relative to controls. These data support the idea that a mild inflammatory signature is evident in MDD and is accompanied by reduced circulating tryptophan concentrations. However, we found no indication of KP activation in the depressed cohort suggesting that an alternative mechanism mediates the depletion of

  11. Naturally occurring pentacyclic triterpenes as inhibitors of glycogen phosphorylase: synthesis, structure-activity relationships, and X-ray crystallographic studies.

    PubMed

    Wen, Xiaoan; Sun, Hongbin; Liu, Jun; Cheng, Keguang; Zhang, Pu; Zhang, Liying; Hao, Jia; Zhang, Luyong; Ni, Peizhou; Zographos, Spyros E; Leonidas, Demetres D; Alexacou, Kyra-Melinda; Gimisis, Thanasis; Hayes, Joseph M; Oikonomakos, Nikos G

    2008-06-26

    Twenty-five naturally occurring pentacyclic triterpenes, 15 of which were synthesized in this study, were biologically evaluated as inhibitors of rabbit muscle glycogen phosphorylase a (GPa). From SAR studies, the presence of a sugar moiety in triterpene saponins resulted in a markedly decreased activity ( 7, 18- 20) or no activity ( 21, 22). These saponins, however, might find their value as potential natural prodrugs which are much more water-soluble than their corresponding aglycones. To elucidate the mechanism of GP inhibition, we have determined the crystal structures of the GPb-asiatic acid and GPb-maslinic acid complexes. The X-ray analysis indicates that the inhibitors bind at the allosteric activator site, where the physiological activator AMP binds. Pentacyclic triterpenes represent a promising class of multiple-target antidiabetic agents that exert hypoglycemic effects, at least in part, through GP inhibition. PMID:18517260

  12. Chromosome 5 allelic losses are early events in tumours of the papilla of Vater and occur at sites similar to those of gastric cancer.

    PubMed Central

    Achille, A.; Baron, A.; Zamboni, G.; Di Pace, C.; Orlandini, S.; Scarpa, A.

    1998-01-01

    During our studies of DNA fingerprinting of tumours of the pancreas and papilla (ampulla) of Vater, using arbitrarily primed polymerase chain reaction (AP-PCR), we noticed two bands showing a decreased intensity in six of ten ampullary tumours with respect to matched normal tissues. Those bands were both assigned to chromosome 5. Such a finding was somewhat in contrast with the reportedly low frequency of APC gene mutations in ampullary cancers, located at chromosome 5q21, and suggested that loci different from that of APC might be the target of chromosome 5 allelic losses (LOH) in these tumours. Therefore, we analysed chromosome 5 LOH in a panel of 27 ampullary tumours, including eight adenomas, four early- and 15 advanced-stage cancers, using 16 PCR-amplified CA microsatellite polymorphic markers spanning the entire chromosome. Nineteen cases (70%) showed LOH, and the interstitial deletions found in these tumours described two smallest common deleted regions, in which putative suppressor genes might reside. They were at 5q13.3-q14 and at 5q23-q31 respectively, which correspond to those found in gastric tumours. In addition, the presence of 5q LOH in six of eight adenomas and in three of four early-stage cancers suggests that such phenomena occur at early stages of neoplastic progression of the ampullary epithelium. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:9862579

  13. Events occurring during the previous lactation, the dry period, and peripartum as risk factors for early lactation mastitis in cows receiving 2 different intramammary dry cow therapies.

    PubMed

    Pinedo, P J; Fleming, C; Risco, C A

    2012-12-01

    The objective of this study was to investigate the association between mastitis events occurring during the previous lactation, the dry period, and the peripartum period on the incidence of early lactation mastitis in cows receiving ceftiofur hydrochloride or penicillin dihydrostreptomycin as intramammary dry cow antibiotic therapy. Cows (n=402) from 2 large dairy farms in Central Florida were enrolled in the study at the time of dry-off processing and were randomly assigned to 1 of 2 dry cow therapies: ceftiofur hydrochloride or penicillin dihydrostreptomycin. Composite milk samples were collected at dry-off and after calving for bacteriological examination and somatic cell count. Peripartal health disorders were monitored during the first 30 d of lactation and included calving difficulty, metritis, ketosis, and left displaced abomasum. Milk production and individual somatic cell scores (SCS) were recorded monthly by the Dairy Herd Improvement Association. The main outcome variables were the risk of clinical mastitis during the first 30 and 60 d of lactation, and the risk of subclinical mastitis at the first 2 monthly Dairy Herd Improvement Association tests after calving (up to 70 d in milk). Additionally, the SCS and the presence of mastitis pathogens in milk at dry-off and at calving were analyzed. Explanatory variables consisted of events occurring during the previous lactation, at dry-off and during the dry period, at calving, and within the first 30 d after calving. Multiple events occurring during the previous lactation had a significant effect on the incidence of mastitis in the subsequent lactation. These events included low milk yield, intermediate lactation length, clinical mastitis, and lactation SCS average. Similarly, intramammary infections with environmental bacteria at dry-off increased the chances of clinical mastitis the first month after calving. Dry-off therapy had a significant effect on mastitis incidence; cows treated with ceftiofur

  14. 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

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

    PubMed

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

    2014-10-01

    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

  16. 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)

  17. Activation of alpha6-containing GABAA receptors by pentobarbital occurs through a different mechanism than activation by GABA.

    PubMed

    Fisher, Matthew T; Fisher, Janet L

    2010-03-01

    The GABA(A) receptors are ligand-gated chloride channels which are the targets for many clinically used sedatives, including the barbiturates. The barbiturate pentobarbital acts through multiple sites on the GABA(A) receptor. At low concentrations (muM), it acts as a positive allosteric modulator while at higher concentrations it can directly activate the receptor. This agonist action is influenced by the subunit composition of the receptor, and pentobarbital is a more effective agonist than GABA only at receptors containing an alpha6 subunit. The conformational change that translates GABA binding into channel opening is known to involve a lysine residue located in an extracellular domain between the 2nd and 3rd transmembrane domains. Mutations of this residue disrupt activation of the channel by GABA and have been linked to inherited epilepsy. Pentobarbital binds to the receptor at a different agonist site than GABA, but could use a common signal transduction mechanism to gate the channel. To address this question, we compared the effect of a mutating the homologous lysine residue in the alpha1 or alpha6 subunits (K278 or K277, respectively) to methionine on direct activation of recombinant GABA(A) receptors by GABA or pentobarbital. We found that this mutation reduced GABA sensitivity for both alpha1 and alpha6 subunits, but affected pentobarbital sensitivity only for the alpha1 subunit. This suggests that pentobarbital acts through a distinct signal transduction pathway at the alpha6 subunit, which may account for its greater efficacy compared to GABA at receptors containing this subunit. PMID:20109529

  18. 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…

  19. Mitotic checkpoint slippage in humans occurs via cyclin B destruction in the presence of an active checkpoint.

    PubMed

    Brito, Daniela A; Rieder, Conly L

    2006-06-20

    In the presence of unattached/weakly attached kinetochores, the spindle assembly checkpoint (SAC) delays exit from mitosis by preventing the anaphase-promoting complex (APC)-mediated proteolysis of cyclin B, a regulatory subunit of cyclin-dependent kinase 1 (Cdk1). Like all checkpoints, the SAC does not arrest cells permanently, and escape from mitosis in the presence of an unsatisfied SAC requires that cyclin B/Cdk1 activity be inhibited. In yeast , and likely Drosophila, this occurs through an "adaptation" process involving an inhibitory phosphorylation on Cdk1 and/or activation of a cyclin-dependent kinase inhibitor (Cdki). The mechanism that allows vertebrate cells to escape mitosis when the SAC cannot be satisfied is unknown. To explore this issue, we conducted fluorescence microscopy studies on rat kangaroo (PtK) and human (RPE1) cells dividing in the presence of nocodazole. We find that in the absence of microtubules (MTs), escape from mitosis occurs in the presence of an active SAC and requires cyclin B destruction. We also find that cyclin B is progressively destroyed during the block by a proteasome-dependent mechanism. Thus, vertebrate cells do not adapt to the SAC. Rather, our data suggest that in normal cells, the SAC cannot prevent a slow but continuous degradation of cyclin B that ultimately drives the cell out of mitosis. PMID:16782009

  20. 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

  1. 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…

  2. Assessment of public exposure to naturally occurring radioactive materials from mining and mineral processing activities of Tarkwa Goldmine in Ghana.

    PubMed

    Faanu, Augustine; Ephraim, James H; Darko, Emmanuel O

    2011-09-01

    Studies have been carried out in a Goldmine in Ghana to determine the exposure of the public to naturally occurring radioactive materials from processing of gold ore. Direct gamma spectrometry and neutron activation analysis techniques were used to analyse soil, rock, water and dust samples from the mining environment. The mean activity concentrations measured for (238)U, (232)Th and (40)K in the soil/rock samples were 15.2, 26.9 and 157.1 Bq kg( - 1), respectively. For the water samples, the mean activity concentrations were 0.54 and 0.41 Bq l( - 1)) and 7.76 Bq l( - 1) for (226)Ra, (232)Th and (40)K, respectively. The mean activity concentrations measured in the dust samples were 4.90 and 2.75 μBq m( - 3) for (238)U and (232)Th, respectively. The total annual effective dose to the public was estimated to be 0.69 mSv. The results in this study compared well with typical world average values. The results indicate an insignificant exposure of the public from the activities of the Goldmine. PMID:21072583

  3. 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)

  4. 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…

  5. 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.

  6. 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…

  7. 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. PMID:26132887

  8. Antiperoxidative, anti-inflammatory, and antimutagenic activities of ethanol extract of the mycelium of Ganoderma lucidum occurring in South India.

    PubMed

    Lakshmi, B; Ajith, T A; Sheena, N; Gunapalan, Nidhi; Janardhanan, K K

    2003-01-01

    Free radical mediated genetic instability is widely thought to be a major etiological factor for initiation of carcinogenesis. Mushrooms represent a largely untapped source of powerful new pharmaceutical products. In the present study, we examined the antiperoxidative, anti-inflammatory, and antimutagenic activities of the ethanol extract of the mycelium of a medicinal mushroom, Ganoderma lucidum, occurring in south India. Antiperoxidative activity was evaluated using Fe(2+)-ascorbate-induced lipid peroxidation in rat liver homogenate and a phorbol ester (croton oil)-induced lipid peroxidation in mouse skin. Antiinflammatory activity was evaluated against carrageenan-induced acute and formalin-induced chronic inflammatory paw edema in mouse and phorbol ester-induced mouse skin inflammation. Antimutagenic activity was determined by the Ames mutagenicity assay using histidine mutant of Salmonella typhimurium strains TA 98, TA100, and TA102. Sodium azide (NaN(3)), N-methyl-N-nitro-N-nitrosoguanidine (MNNG), 4-nitro-o-phenylenediamine (NPD), and benzo[a]pyrene (B[a]P) were used as the mutagens. The extract showed significant inhibition of Fe(2+)-induced peroxidation of lipid in rat liver (IC(50) 510 +/- 22 microg/ml) and 37% inhibition of croton oil-induced peroxidation on the mouse skin at 20 mg/0.1 ml/skin. Carrageenan-induced acute and formalin-induced chronic inflammatory edema were inhibited by 56 and 60%, respectively, by the extract at 1,000 mg/kg body wt (i.p). The extract at a concentration of 5 mg/plate showed inhibition of mutagenicity elicited by direct acting mutagens, NaN(3) (55.5 and 75.7%) and MNNG (50.0 and 57.5%) for S. typhymurium strains TA100 and TA102, respectively. The extract at the same concentration also inhibited mutagenicity elicited by NPD (52.4 and 64.2%) and B[a]P (60.7 and 59.6%) for TA98 and TA100 strains, respectively. The B[a]P was activated in the presence of rat liver microsomal (S9) fraction. The results of our study revealed that

  9. 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

  10. Workjobs II: Number Activities for Early Childhood.

    ERIC Educational Resources Information Center

    Baratta-Lorton, Mary

    This curriculum guide presents a program of 20 open-ended math activities to be used to supplement the math programs in kindergarten, first, or second grade classrooms. The program consists of child-oriented counters and gameboards used to explore the concept of number from counting to making up and solving addition and subtraction equations. Each…

  11. 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,…

  12. A Nonselective Cyclooxygenase Inhibitor Enhances the Activity of Vinblastine in a Naturally-Occurring Canine Model of Invasive Urothelial Carcinoma

    PubMed Central

    Knapp, Deborah W.; Ruple-Czerniak, Audrey; Ramos-Vara, José A.; Naughton, James F.; Fulkerson, Christopher M.; Honkisz, Sonia I.

    2016-01-01

    Background: Chemotherapy is expected to remain an important part of invasive urothelial carcinoma (UC) treatment. Strategies to enhance chemotherapy efficacy are needed. Objective: To determine the chemotherapy-enhancing effects of a nonselective cyclooxygenase (COX) inhibitor on vinblastine in a naturally-occurring canine model of invasive UC. Methods: With IACUC approval, privately-owned dogs with naturally-occurring histologically-diagnosed invasive UC, expected survival ≥6 weeks, and informed owner consent were randomly allocated to receive vinblastine (2.5 mg/m2 intravenously every 2 weeks) plus piroxicam (0.3 mg/kg daily per os) or vinblastine alone (same dose) with the option to receive piroxicam alone when vinblastine failed. Scheduled evaluations included physical exam, standard laboratory analyses, thoracic radiography, abdominal ultrasonography, and standardized measurement of urinary tract tumors. Results: Dogs receiving vinblastine alone (n = 27) and vinblastine-piroxicam (n = 24) were similar in age, sex, breed, tumor stage, and grade. Remission occurred more frequently (P <  0.02) with vinblastine-piroxicam (58.3%) than with vinblastine alone (22.2%). The median progression free interval was 143 days with vinblastine alone and 199 days with the combination. Interestingly, the overall median survival time was significantly longer (P <  0.03) in dogs receiving vinblastine alone followed by piroxicam alone (n = 20, 531 days) than in dogs receiving the combination (299 days). Treatment was well tolerated in both arms. Conclusions: Piroxicam significantly enhanced the activity of vinblastine in dogs with UC where the cancer closely mimics the human condition, clearly justifying further study. The study suggest the potential importance of tracking COX inhibitor use in patients in clinical trials as COX inhibitors could affect treatment response. PMID:27376143

  13. Fusion activity of African henipavirus F proteins with a naturally occurring start codon directly upstream of the signal peptide.

    PubMed

    Weis, Michael; Behner, Laura; Binger, Tabea; Drexler, Jan Felix; Drosten, Christian; Maisner, Andrea

    2015-04-01

    Compared to the fusion proteins of pathogenic Nipah and Hendra viruses, the F protein of prototype African henipavirus GH-M74a displays a drastically reduced surface expression and fusion activity. A probable reason for limited F expression is the unusually long sequence located between the gene start and the signal peptide (SP) not present in other henipaviruses. Such a long pre-SP extension can prevent efficient ER translocation or protein maturation and processing. As its truncation can therefore enhance surface expression, the recent identification of a second in-frame start codon directly upstream of the SP in another African henipavirus F gene (GH-UP28) raised the question if such a naturally occurring minor sequence variation can lead to the synthesis of a pre-SP truncated translation product, thereby increasing the production of mature F proteins. To test this, we analyzed surface expression and biological activity of F genes carrying the second SP-proximal start codon of GH-UP28. Though we observed minor differences in the expression levels, introduction of the additional start codon did not result in an increased fusion activity, even if combined with further mutations in the pre-SP region. Thus, limited bioactivity of African henipavirus F protein is maintained even after sequence changes that alter the gene start allowing the production of F proteins without an unusually long pre-SP. PMID:25725148

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

    PubMed

    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

  15. 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

  16. 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

  17. Therapeutic potentials occurring during the early differentiation process of mesenchymal stem cells in a rats model with thioacetamide-induced liver fibrosis

    PubMed Central

    Choi, Sang-Tae; Hong, Hea-Nam; Won, You-Jin; Ahn, Chul-Soo; Ha, Tae-Yong; Song, Gi-Won; Jung, Dong-Hwan; Park, Gil-Chun; Lee, Sung-Gyu

    2013-01-01

    Backgrounds/Aims Mesenchymal stem cells (MSCs) have the capacity to differentiate into hepatocytes, The purpose of this study is to investigate the MSCs' differentiation process and therapeutic potentials by comparing isolated MSCs with HGF-treated MSCs in rat's model with thiacetamide (TAA)-induced cirrhosis. Methods Male Sprague-Dawley (SD) rats, weighing 100-150 g were used in this study. To induce liver fibrosis, recipient rats were taken with 0.04% thioacetamide (TAA) in the drinking water (400 mg TAA/L) for 8 weeks. The rats underlying liver cirrhosis were divided into 3 groups according to the transplanted materials, compared to normal saline as control (I) and isolated MSCs (II) HGF-treated MSCs. Results Severe hepatic fibrosis and hepatocyte destruction were detected in the control group. Less hepatic cirrhosis and collagen formation, more hepatocyte regeneration and glycogen storage were detected in isolated MSCs compared to HGF-treated MSCs group, Distribution of red autofluorescence is mainly localized near the sinusoids in isolated MSCs, scattered away the sinusoids in HGF-treated MSCs group. MSCs transdifferentiated into CK-19 postive Oval cells and then to albulmin-producing hepatocytes, HGF treated MSCs differentiated into hepatocyte without the intermediate oval cells phase. HGF treated MSCs became the CK18-positive, MSCs became CD 90-positive. Conclusions Significant hepatocyte differentiation occurred in not HGF-treated MSCs but isolated MSCs group unexpectedly. These results suggest that the beneficial effect of MSCs on in rat's model with TAA-induced cirrhosis may occur during early differentiation course of MSCs. Mature hepatocyte itself has a little effect on the accelerated differentiation and functional capacity of hepatic lineage cell-line. PMID:26155209

  18. 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

  19. Impact of viral activators and epigenetic regulators on HIV-1 LTRs containing naturally occurring single nucleotide polymorphisms.

    PubMed

    Shah, Sonia; Pirrone, Vanessa; Alexaki, Aikaterini; Nonnemacher, Michael R; Wigdahl, Brian

    2015-01-01

    Following human immunodeficiency virus type 1 (HIV-1) integration into host cell DNA, the viral promoter can become transcriptionally silent in the absence of appropriate signals and factors. HIV-1 gene expression is dependent on regulatory elements contained within the long terminal repeat (LTR) that drive the synthesis of viral RNAs and proteins through interaction with multiple host and viral factors. Previous studies identified single nucleotide polymorphisms (SNPs) within CCAAT/enhancer binding protein (C/EBP) site I and Sp site III (3T, C-to-T change at position 3, and 5T, C-to-T change at position 5 of the binding site, respectively, when compared to the consensus B sequence) that are low affinity binding sites and correlate with more advanced stages of HIV-1 disease. Stably transfected cell lines containing the wild type, 3T, 5T, and 3T5T LTRs were developed utilizing bone marrow progenitor, T, and monocytic cell lines to explore the LTR phenotypes associated with these genotypic changes from an integrated chromatin-based microenvironment. Results suggest that in nonexpressing cell clones LTR-driven gene expression occurs in a SNP-specific manner in response to LTR activation or treatment with trichostatin A treatment, indicating a possible cell type and SNP-specific mechanism behind the epigenetic control of LTR activation. PMID:25629043

  20. Attempted Cell Cycle Induction in Post-Mitotic Neurons Occurs in Early and Late Apoptotic Programs Through Rb, E2F1, and Caspase 3

    PubMed Central

    Chong, Zhao Zhong; Li, Faqi; Maiese, Kenneth

    2007-01-01

    Either the absence or dysfunction of a number of critical pathways, such as those that involve the nuclear retinoblastoma protein (Rb) and the transcription factor E2F1, may account for the aberrant induction of the cell cycle in post-mitotic neurons that can be responsible for oxidative stress-induced apoptotic cellular destruction. Yet, it is unclear whether early programs of apoptotic injury that involve membrane phosphatidylserine (PS) exposure and calreticulin expression as well as later phases of apoptotic injury with nuclear DNA injury require the critical modulation of Rb and E2F1. We demonstrate that both the post-translational of phosphorylation of Rb to prevent E2F1 transcription as well as the protein integrity of Rb are closely aligned with the modulation of cell cycle induction in post mitotic neurons during oxidative stress. More importantly, we illustrate that both the initial onset of apoptosis with either membrane PS exposure or calreticulin analysis as well as the more terminal phases of apoptosis that involve nuclear DNA degradation proceed concurrently in the same neuronal cells with cell cycle induction. Progression of attempted cell cycle induction is closely associated with the phosphorylation of Rb, its inability to bind to E2F1, and the degradation of the Rb protein. Inhibition of Rb phosphorylation using cyclin dependent kinase inhibitors maintains the integrity of the E2F1/Rb complex and is neuroprotective during free radical exposure. Furthermore, maintenance of the integrity of the Rb protein is specifically dependent upon caspase 3-like activity, since caspase 3 can cleave Rb during free radical activity and this degradation of Rb can be blocked during the inhibition of caspase 3 activity. Our studies not only highlight the critical role of attempted cell cycle induction during oxidative stress-induced neuronal apoptotic injury, but also bring to light the significant impact of the Rb and E2F1 pathways upon early apoptotic programs

  1. Early capillary flux homogenization in response to neural activation.

    PubMed

    Lee, Jonghwan; Wu, Weicheng; Boas, David A

    2016-02-01

    This Brief Communication reports early homogenization of capillary network flow during somatosensory activation in the rat cerebral cortex. We used optical coherence tomography and statistical intensity variation analysis for tracing changes in the red blood cell flux over hundreds of capillaries nearly at the same time with 1-s resolution. We observed that while the mean capillary flux exhibited a typical increase during activation, the standard deviation of the capillary flux exhibited an early decrease that happened before the mean flux increase. This network-level data is consistent with the theoretical hypothesis that capillary flow homogenizes during activation to improve oxygen delivery. PMID:26661145

  2. 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…

  3. 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…

  4. Naturally-occurring compensated insulin resistance selectively alters glucose transporters in visceral and subcutaneous adipose tissue without change in AS160 activation

    PubMed Central

    Waller, AP; Kohler, K; Burns, TA; Mudge, MC; Belknap, JK; Lacombe, VA

    2011-01-01

    Although the importance of adipose tissue (AT) glucose transport in regulating whole-body insulin sensitivity is becoming increasingly evident and insulin resistance (IR) has been widely recognized, the underlying mechanisms of IR are still not well understood. The purpose of the present study was to determine the early pathological changes in glucose transport by characterizing the alterations in glucose transporters (GLUT) in multiple visceral and subcutaneous adipose depots in a large animal model of naturally-occurring compensated IR. AT biopsies were collected from horses, which were classified as insulin-sensitive (IS) or compensated IR based on the results of an insulin-modified frequently-sampled intravenous glucose tolerance test. Protein expression of GLUT4 (major isoform) and GLUT12 (one of the most recently discovered isoforms) were measured by Western blotting in multiple AT depots, as well as AS160 (a potential key player in GLUT trafficking pathway). Using a biotinylated bis-mannose photolabeled technique, active cell surface GLUT content was quantified. Omental AT had the highest total GLUT content compared to other sites during the IS state. IR was associated with a significantly reduced total GLUT4 content in omental AT, without a change in content in other visceral or subcutaneous adipose sites. In addition, active cell surface GLUT-4, but not -12, was significantly lower in AT of IR compared to IS horses, without change in AS160 phosphorylation between groups. Our data suggest that GLUT4, but not GLUT12, is a pathogenic factor in AT during naturally-occurring compensated IR, despite normal AS160 activation. PMID:21352908

  5. Skeletal muscle wasting occurs in adult rats under chronic treatment with paracetamol when glutathione-dependent detoxification is highly activated.

    PubMed

    Mast, C; Joly, C; Savary-Auzeloux, I; Remond, D; Dardevet, D; Papet, I

    2014-10-01

    The use of glutathione (GSH) and sulfate for the detoxification of paracetamol (acetaminophen, APAP) could occur at the expense of the physiological uses of cysteine (Cys). Indeed GSH and sulfate both originate from Cys. Significant APAP-induced Cys loss could generate alterations in GSH and protein metabolisms leading to muscle wasting. The study aimed to investigate the effects of chronic treatment with APAP on whole-body and tissue homeostasis (mass, GSH, proteins, and nitrogen balance) in relation to sulfur losses through APAP-detoxification pathways. Adult male Wistar rats were fed 0% APAP, 0.5% APAP or 1% APAP diets for 17 days. APAP doses were respectively around and largely above the threshold of sulfation saturation for rats. During the last days, the rats were placed in metabolic cages in order to quantify N balance and urinary APAP metabolites. Gastrocnemius muscle mass, protein and GSH contents, N balance and plasma free cyst(e)ine were 8% (P=0.02), 7% (P=0.03), 26% (P=0.01), 37% (P=0.01), and 33% (P=0.003) lower in the 1% APAP group than in the 0% APAP group, respectively. There was no significant difference in these parameters between the 0.5% APAP group and the 0% APAP group. Muscle wasting occurred when the detoxification of APAP through the GSH-dependent pathway was highly activated. Muscle protein synthesis could have been reduced due to a shortage in Cys and/or an increase in protein degradation in response to intra-muscular oxidative stress. Hence, without dietary sulphur amino acid increase, peripheral bioavailability of Cys and muscle GSH are potential players in the control of muscle mass under chronic treatment with APAP, an analgesic medication of widespread use, especially in the elderly. PMID:25371521

  6. 4,6-α-Glucanotransferase activity occurs more widespread in Lactobacillus strains and constitutes a separate GH70 subfamily.

    PubMed

    Leemhuis, Hans; Dijkman, Willem P; Dobruchowska, Justyna M; Pijning, Tjaard; Grijpstra, Pieter; Kralj, Slavko; Kamerling, Johannis P; Dijkhuizen, Lubbert

    2013-01-01

    Family 70 glycoside hydrolase glucansucrase enzymes exclusively occur in lactic acid bacteria and synthesize a wide range of α-D-glucan (abbreviated as α-glucan) oligo- and polysaccharides. Of the 47 characterized GH70 enzymes, 46 use sucrose as glucose donor. A single GH70 enzyme was recently found to be inactive with sucrose and to utilize maltooligosaccharides [(1→4)-α-D-glucooligosaccharides] as glucose donor substrates for α-glucan synthesis, acting as a 4,6-α-glucanotransferase (4,6-αGT) enzyme. Here, we report the characterization of two further GH70 4,6-αGT enzymes, i.e., from Lactobacillus reuteri strains DSM 20016 and ML1, which use maltooligosaccharides as glucose donor. Both enzymes cleave α1→4 glycosidic linkages and add the released glucose moieties one by one to the non-reducing end of growing linear α-glucan chains via α1→6 glycosidic linkages (α1→4 to α1→6 transfer activity). In this way, they convert pure maltooligosaccharide substrates into linear α-glucan product mixtures with about 50% α1→6 glycosidic bonds (isomalto/maltooligosaccharides). These new α-glucan products may provide an exciting type of carbohydrate for the food industry. The results show that 4,6-αGTs occur more widespread in family GH70 and can be considered as a GH70 subfamily. Sequence analysis allowed identification of amino acid residues in acceptor substrate binding subsites +1 and +2, differing between GH70 GTF and 4,6-αGT enzymes. PMID:22361861

  7. Early active mobilization following UCL repair With Mitek bone anchor.

    PubMed

    Crowley, Timothy P; Stevenson, Susan; Taghizadeh, Reika; Addison, Patrick; Milner, Richard H

    2013-09-01

    Ulnar collateral ligament (UCL) injuries of the thumb are common. Surgical repair is accepted as the treatment of choice for complete rupture of the ligament. Biomechanical studies have suggested that Mitek bone anchor repairs are potentially safe and strong enough to allow early controlled active mobilization. To date, there have been no studies to compare early active mobilization following Mitek bone anchor repair to standard postoperative rehabilitation involving thumb spica immobilization for the first 4 to 6 weeks. We performed a small pilot randomized control trial to assess the outcome of this new rehabilitation technique to that of standard immobilization following UCL repair with Mitek bone anchor. Our results show that on average early active mobilization leads to an earlier return to full hand function (6 vs. 8 wk) and an earlier return to work (7 vs. 11 wk). There is no difference in the final range of motion achieved. We suggest that Mitek bone anchor repairs for UCL ruptures are robust enough to allow early active mobilization and that a larger trial is warranted to assess whether early active mobilization is superior to standard rehabilitation. PMID:23970193

  8. 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

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

    PubMed

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

    2016-05-13

    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 44weeks, 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

  10. 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. PMID:21813711

  11. 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

  12. 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.

  13. Sigmoid colonic metastasis by lymphatic spread occurring with unilateral Krukenberg tumor considered to be caused by stage IA early gastric cancer: A case report

    PubMed Central

    FUJIMOTO, DAISUKE; HIRONO, YASUO; GOI, TAKANAORI; YAMAGUCHI, AKIO

    2016-01-01

    Gastric cancer is one of the most common malignancies in Asia, and the second most common cause of cancer-associated mortality in Japan. Colorectal metastases originating from gastric adenocarcinoma are extremely rare. The present study reports an unusual case of lymphogenous sigmoid metastasis of gastric adenocarcinoma occurring in a 58-year-old female patient. Endoscopic and radiological findings were indicative of 0-IIc+IIa early gastric cancer, and radical distal gastrectomy with D2 lymph node dissection was performed. The pathological diagnosis was stage IA gastric adenocarcinoma (T1bN0M0), according to the Japanese classification of gastric cancer. A follow-up examination at 18 months post surgery revealed a recurrence of paraaortic lymph node metastasis, detected by abdominal computed tomography (CT) and positron emission tomography (PET)/CT. The patient received chemotherapy with S-1 and cisplatin. Subsequently, radiotherapy was administered to the paraaortic lymph nodes at levels Th11-L3. Follow-up abdominal CT and PET/CT revealed an enlarged left ovary, and abnormal uptake in the left ovary and sigmoid colon. An oophorectomy and sigmoidectomy with D3 lymph node dissection were performed. The pathological diagnosis was metastatic adenocarcinoma; this was identical to the gastric pathology in the previous pathological report. The patient continued treatment with chemotherapy. Although sigmoid colonic metastasis from gastric cancer is extremely rare, metastasis from gastric cancer must be considered during the differential diagnosis of cases involving a colorectal mass and a previous history of gastric cancer. PMID:26870264

  14. 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

  15. Communicating and Thinking through Drawing Activity in Early Childhood

    ERIC Educational Resources Information Center

    Papandreou, Maria

    2014-01-01

    This article considers drawing as a meaning-making activity that takes place in certain sociocultural contexts to find evidence for its communicative potentials as well as the relationship between thought and drawing in early childhood. The researcher challenges traditional views about young children's drawing that focus on the result of the…

  16. Teaching Adults, Revisited: Active Learning for Early Childhood Educators

    ERIC Educational Resources Information Center

    Jones, Elizabeth

    2007-01-01

    This book follows master educator Elizabeth (Betty) Jones as she teaches an introductory course in early childhood education. She actively engages the students, encouraging them to make decisions, ask questions, and engage in collaborative problem solving--herself modeling the behaviors that should be practiced by adults working with young…

  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. 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

  19. An Immediate Innate Immune Response Occurred In the Early Stage of E.granulosus Eggs Infection in Sheep: Evidence from Microarray Analysis

    PubMed Central

    Tang, Jishun; Hou, Hongyan; Chen, Sheng; Jia, Bin; Ban, Qian

    2015-01-01

    Background Cystic Echinococcosis(CE), caused by infection with the larval stage of the cestode Echinococcus granulosus (E. granulosus), is a chronic parasitic zoonosis, with highly susceptible infection in sheep. However, the comprehensive molecular mechanisms that underlie the process of E. granulosus infection in the early stage remain largely unknown. The objective of this present study was to gain a cluster of genes expression profiles in the intestine tissue of sheep infected with CE. Methods Nine healthy sheep were divided into infection group and healthy controls, with six infected perorally 5000 E. granulosus eggs suspended in 1000μl physiological saline and three controls perorally injected 1000μl physiological saline. All animals were sacrificed at 4 hours post-infection, respectively. The intestine tissue was removed and the RNA was extracted. In the infection group, the biology replicates were designed to make sure the accuracy of the data. The ovine microarrays were used to analyze changes of gene expression in the intestine tissue between CE infected sheep and healthy controls. Real-time PCR was used to assess reliability of the microarray data. Results By biology repeats, a total of 195 differentially expressed genes were identified between infected group and controls at 4 hours post-infection, with 105 genes related to immune responses, while 90 genes associated with functions including energy metabolism, fat soluble transport, etc. Among the 105 immunity genes, 72 genes showed up-regulated expression levels while 33 showed down-regulation levels. Function analysis showed that most of up-regulated genes were related to innate immune responses, such as mast cell, NK cell, cytokines, chemokines and complement. In addition, Real-time PCR analysis of a random selection of nine genes confirmed the reliability of the microarray data. Conclusion To our knowledge, this is the first report describing gene expression profiles in the intestine tissue of CE

  20. Activity size distributions of some naturally occurring radionuclides 7Be, 40K and 212Pb in indoor and outdoor environments.

    PubMed

    Mohamed, A

    2005-05-01

    The activity size distributions of natural radionuclides (7)Be and (40)K were measured outdoor in El-Minia city, Egypt by means of gamma spectroscopy. A low-pressure Berner cascade impactor was used as a sampling device. The activity size distribution of both (7)Be and (40)K was described by one log-normal distribution, which was represented by the accumulation mode. The activity median aerodynamic diameter (AMAD) of (7)Be and (40)K was determined to be 530 and 1550 nm with a relative geometric standard deviation (delta, which was defined as the dispersion of the peak) of 2.4 and 2, respectively. The same sampling device (Berner impactor) and a screen diffusion battery were used to measure the activity size distribution, activity concentration and unattached fraction (f(P)) of (212)Pb in indoor air of El-Minia City, Egypt. The mean activity median aerodynamic diameter (AMAD) of the accumulation mode for attached (212)Pb was determined to be 250 nm with a mean geometric standard deviation (delta) of 2.6. The mean value of the specific concentration of (212)Pb associated with that mode was determined to be 460+/-20 mBq m(-3). The activity median thermodynamic diameter (AMTD) of unattached (212)Pb was determined to be 1.25 nm with delta of 1.4. A mean unattached fraction (f(p)) of 0.13+/-0.02 was obtained at a mean aerosol particle concentration of 1.8 x 10(3) cm(-3). The mean activity concentration of unattached (212)Pb was found to be 19+/-3 mBq m(-3). It was found that the aerosol concentration played an important role in varying the unattached, attached activity concentration and unattached fraction (f(P)). PMID:15763482

  1. Nuclear entry and nucleolar localization of the Newcastle disease virus (NDV) matrix protein occur early in infection and do not require other NDV proteins.

    PubMed Central

    Peeples, M E; Wang, C; Gupta, K C; Coleman, N

    1992-01-01

    A large proportion of the Newcastle disease virus (NDV) matrix (M) protein is found in the nuclei of infected chicken embryo cells. Kinetic analysis indicated that much of the M protein enters the nucleus early in infection, concentrating in discrete regions of the nucleus and remaining there throughout infection. The M protein was found in localized regions of the nuclei of a variety of cell lines infected with NDV. Immunostaining for both M protein and nucleolar antigens indicated that most of these regions represent nucleoli. Moreover, this nucleolar localization of the M protein was observed in chicken embryo cells infected with 11 different strains of NDV. Only the M protein of strain HP displayed a modified pattern, concentrating in the nucleolus early in infection but in the cytoplasm late in infection. M protein transiently expressed in COS-1 cells also localized to the nucleus and nucleolus, indicating that the M protein does not require other NDV proteins for this localization. Images PMID:1560547

  2. Early Interfaced Neural Activity from Chronic Amputated Nerves

    PubMed Central

    Garde, Kshitija; Keefer, Edward; Botterman, Barry; Galvan, Pedro; Romero, Mario I.

    2009-01-01

    Direct interfacing of transected peripheral nerves with advanced robotic prosthetic devices has been proposed as a strategy for achieving natural motor control and sensory perception of such bionic substitutes, thus fully functionally replacing missing limbs in amputees. Multi-electrode arrays placed in the brain and peripheral nerves have been used successfully to convey neural control of prosthetic devices to the user. However, reactive gliosis, micro hemorrhages, axonopathy and excessive inflammation currently limit their long-term use. Here we demonstrate that enticement of peripheral nerve regeneration through a non-obstructive multi-electrode array, after either acute or chronic nerve amputation, offers a viable alternative to obtain early neural recordings and to enhance long-term interfacing of nerve activity. Non-restrictive electrode arrays placed in the path of regenerating nerve fibers allowed the recording of action potentials as early as 8 days post-implantation with high signal-to-noise ratio, as long as 3 months in some animals, and with minimal inflammation at the nerve tissue-metal electrode interface. Our findings suggest that regenerative multi-electrode arrays of open design allow early and stable interfacing of neural activity from amputated peripheral nerves and might contribute towards conveying full neural control and sensory feedback to users of robotic prosthetic devices. PMID:19506704

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

    PubMed Central

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

    2015-01-01

    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-Myc13 localization, heretofore unrecognized functions for these proteins; and (iv) the importance of

  4. 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

  5. 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

  6. 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…

  7. [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

  8. Phosphorylation and internalization of gp130 occur after IL-6 activation of Jak2 kinase in hepatocytes.

    PubMed Central

    Wang, Y; Fuller, G M

    1994-01-01

    Recent evidence has shown that members of the Jak kinase family are activated after IL-6 binds to its receptor complex, leading to a tyrosine phosphorylation of gp130, the IL-6 signal-transducing subunit. The different members of the IL-6 cytokine subfamily induce distinct patterns of Jak-Tyk phosphorylation in different cell types. Using monospecific antibodies to gp130, Jak2 kinase, and phosphotyrosine, we investigated the kinetics of IL-6 stimulation of members of this pathway in primary hepatocytes. Our findings show that Jak 2 is maximally activated within 2 min of exposure to IL-6, followed by gp130 phosphorylation that reaches its peak in another 2 min then declines to basal level by 60 min. In vitro phosphorylation experiments show that activated Jak 2 is able to phosphorylate both native gp130 and a fusion peptide containing its cytoplasmic domain, demonstrating gp130 is a direct substrate of Jak 2 kinase. Experiments designed to explore the cell surface expression of gp130 show that > or = 2 h are required to get a second round of phosphorylation after the addition of more cytokines. This finding suggests that activated gp130 is internalized from the cell surface after IL-6 stimulation. Additional experiments using protein synthesis inhibitors reveal that new protein synthesis is required to get a second cycle of gp130 phosphorylation indicating gp130 must be synthesized de novo and inserted into the membrane. These findings provide strong evidence that down regulation of the IL-6 signal in hepatocytes involves the internalization and cytosol degradation of gp130. Images PMID:7812050

  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

    2016-01-01

    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

  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. Antimicrobial activity of plumbagin, a naturally occurring naphthoquinone from Plumbago rosea, against Staphylococcus aureus and Candida albicans.

    PubMed

    Nair, Sweatha V; Baranwal, Gaurav; Chatterjee, Maitrayee; Sachu, Arun; Vasudevan, Anil Kumar; Bose, Chinchu; Banerji, Asoke; Biswas, Raja

    2016-06-01

    Candida albicans and Staphylococcus aureus are opportunistic pathogens. Despite causing a number of independent infections, both pathogens can co-infect to cause urinary tract infections, skin infections, biofilm associated infections, sepsis and pneumonia. Infections of these two pathogens especially their biofilm associated infections are often difficult to treat using currently available anti-bacterial and anti-fungal agents. In order to identify a common anti-microbial agent which could confer a broad range of protection against their infections, we screened several phytochemicals and identified plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), a phytochemical from Plumbago species as a potent antimicrobial agent against S. aureus and C. albicans, with a minimum inhibitory concentration of 5μg/ml. Antimicrobial activity of plumbagin was validated using an ex-vivo porcine skin model. For better understanding of the antimicrobial activity of plumbagin, a Drosophila melanogaster infection model was used, where D. melanogaster was infected using S. aureus and C. albicans, or with both organisms. The fly's survival rate was dramatically increased when infected flies were treated using plumbagin. Further, plumbagin was effective in preventing and dispersing catheter associated biofilms formed by these pathogens. The overall results of this work provides evidence that plumbagin, possesses an excellent antimicrobial activity which should be explored further for the treatment of S. aureus and C. albicans infections. PMID:27212459

  12. Characterization of the biological activity of gamma-glutamyl-Se-methylselenocysteine: a novel, naturally occurring anticancer agent from garlic.

    PubMed

    Dong, Y; Lisk, D; Block, E; Ip, C

    2001-04-01

    Gamma-glutamyl-Se-methylselenocysteine (GGMSC) has recently been identified as the major Se compound in natural garlic and selenized garlic. Our working hypothesis is that GGMSC serves primarily as a carrier of Se-methylselenocysteine (MSC), which has been demonstrated in past research to be a potent cancer chemopreventive agent in animal carcinogenesis bioassays. The present study was designed to examine the in vivo responses to GGMSC or MSC using a variety of biochemical and biological end points, including (a) urinary Se excretion as a function of bolus dose; (b) tissue Se accumulation profile; (c) anticancer efficacy; and (d) gene expression changes as determined by cDNA array analysis. Our results showed that like MSC, GGMSC was well absorbed p.o., with urinary excretion as the major route for eliminating excess Se. When fed chronically, the profile of Se accumulation in various tissues was very comparable after treatment with either GGMSC or MSC. In rats that had been challenged with a carcinogen, supplementation with either GGMSC or MSC resulted in a lower prevalence of premalignant lesions in the mammary gland, and fewer mammary carcinomas when these early lesions were allowed to progress. More importantly, we found that a short term GGMSC/MSC treatment schedule of 4 weeks immediately after carcinogen dosing was sufficient to provide significant cancer protection, even in the absence of a sustained exposure past the initial 4-week period. With the use of the Clontech Atlas Rat cDNA Array, we further discovered that the gene expression changes induced in mammary epithelial cells of rats that were given either GGMSC or MSC showed a high degree of concordance. On the basis of the collective biology, biochemistry, and molecular biology data, we conclude that GGMSC is an effective anticancer agent with a mechanism of action very similar to that of MSC. PMID:11306469

  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. Pathologic Heterogeneity Persists in Early Active Multiple Sclerosis Lesions

    PubMed Central

    Metz, Imke; Weigand, Stephen D; Popescu, Bogdan F G; Frischer, Josa M; Parisi, Joseph E; Guo, Yong; Lassmann, Hans; Brück, Wolfgang; Lucchinetti, Claudia F.

    2014-01-01

    Objective Multiple sclerosis (MS) lesions demonstrate immunopathological heterogeneity in patterns of demyelination. Previous cross-sectional studies reported immunopatterns of demyelination were identical among multiple active demyelinating lesions from the same individual, but differed between individuals, leading to the hypothesis of intraindividual pathological homogeneity and interindividual heterogeneity. Other groups suggested a time-dependent heterogeneity of lesions. The objective of our present study was to analyze tissue samples collected longitudinally to determine whether patterns of demyelination persist over time within a given patient. Methods Archival tissue samples derived from patients with pathologically confirmed CNS inflammatory demyelinating disease who had undergone either diagnostic serial biopsy or biopsy followed by autopsy, were analyzed immunohistochemically. Inclusion criteria was the presence of early active demyelinating lesions - required for immunopattern classification - obtained from the same patient at two or more time points. Results Among 1321 surgical biopsies consistent with MS, 22 cases met study inclusion criteria. Twenty-one patients (95%) showed a persistence of immunopathological patterns in tissue sampled from different time points. This persistence was demonstrated for all major patterns of demyelination. A single patient showed features suggestive of both pattern II and pattern III on biopsy, but only pattern II among all active lesions examined at autopsy. Interpretation These findings continue to support the concept of patient-dependent immunopathological heterogeneity in early MS and suggest that the mechanisms and targets of tissue injury may differ among patient subgroups. These observations have potentially significant implications for individualized therapeutic approaches. PMID:24771535

  16. 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

  17. In vivo anti-inflammatory activity of some naturally occurring O- and N-prenyl secondary metabolites.

    PubMed

    Epifano, Francesco; Genovese, Salvatore; Fiorito, Serena; della Loggia, Roberto; Tubaro, Aurelia; Sosa, Silvio

    2014-01-01

    A series of O- and N-prenyl secondary metabolites of insect, fungal, and plant origin have been evaluated for their topical anti-inflammatory activity using the Croton oil ear test in mice as a model of acute inflammation. Some of the tested compounds revealed an effect (ID50 = 0.31 divided by 0.56 micromol/cm2) comparable with that of the reference non-steroidal anti-inflammatory drug indomethacin (ID50 = 0.23 micromol/cm2). PMID:24660470

  18. 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

  19. 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.

  20. Enhancement in leaf photosynthesis and upregulation of rubisco in the C4 sorghum plant at elevated growth carbon dioxide and temperature occur at early stages of leaf ontogeny.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Grain sorghum was grown at 350 and 700 (high) ppm CO2, and at daytime maximum/nighttime minimum temperatures of 30/20 and 36/26C. Gas exchange rates, activities of Rubisco and PEP carboxylase (PEPC), leaf area, and biomass of various plant components were determined at different stages of leaf and p...

  1. Selective Phthalate Activation of Naturally Occurring Human Constitutive Androstane Receptor Splice Variants and the Pregnane X Receptor

    PubMed Central

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

    2011-01-01

    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. PMID:21227907

  2. 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. PMID:21227907

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. Development of the Mouse Dermal Adipose Layer Occurs Independently of Subcutaneous Adipose Tissue and Is Marked by Restricted Early Expression of FABP4

    PubMed Central

    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. PMID:23555789

  9. Early Surrogate Markers of Treatment Activity: Where Are We Now?

    PubMed

    Klintman, Marie; Dowsett, Mitchell

    2015-05-01

    The assessment of new therapies in the adjuvant setting in early breast cancer requires large numbers of patients and many years of follow-up for results to be presented. Therefore, the neoadjuvant study setting, which allows for early prediction of treatment response in smaller patient sets, has become increasingly popular. Ki67 is the most commonly used and extensively studied intermediate biomarker of treatment activity and residual risk in neoadjuvant trials on endocrine therapy, new biological therapies, and chemotherapy. It is increasingly being used as a primary endpoint for new therapies particularly those added to endocrine therapy. The PeriOperative Endocrine Therapy for Individualizing Care (POETIC) trial, including more than 4000 postmenopausal, estrogen receptor (ER)-positive patients randomly assigned to receive 2 weeks of presurgical treatment with an aromatase inhibitor or no further treatment, is the largest window-of-opportunity trial conducted and is assessing the clinical utility of on-treatment Ki67 as a predictor of long-term outcome. For generalizability, Ki67 measurements in the POETIC and other trials need to use standard methodology. The International Working Group on Ki67 in Breast Cancer is conducting a series of studies to bring this to reality. PMID:26063881

  10. Early age-dependent impairments of context-dependent extinction learning, object recognition, and object-place learning occur in rats.

    PubMed

    Wiescholleck, Valentina; Emma André, Marion Agnès; Manahan-Vaughan, Denise

    2014-03-01

    The hippocampus is vulnerable to age-dependent memory decline. Multiple forms of memory depend on adequate hippocampal function. Extinction learning comprises active inhibition of no longer relevant learned information concurrent with suppression of a previously learned reaction. It is highly dependent on context, and evidence exists that it requires hippocampal activation. In this study, we addressed whether context-based extinction as well as hippocampus-dependent tasks, such as object recognition and object-place recognition, are equally affected by moderate aging. Young (7-8 week old) and older (7-8 month old) Wistar rats were used. For the extinction study, animals learned that a particular floor context indicated that they should turn into one specific arm (e.g., left) to receive a food reward. On the day after reaching the learning criterion of 80% correct choices, the floor context was changed, no reward was given and animals were expected to extinguish the learned response. Both, young and older rats managed this first extinction trial in the new context with older rats showing a faster extinction performance. One day later, animals were returned to the T-maze with the original floor context and renewal effects were assessed. In this case, only young but not older rats showed the expected renewal effect (lower extinction ratio as compared to the day before). To assess general memory abilities, animals were tested in the standard object recognition and object-place memory tasks. Evaluations were made at 5 min, 1 h and 7 day intervals. Object recognition memory was poor at short-term and intermediate time-points in older but not young rats. Object-place memory performance was unaffected at 5 min, but impaired at 1 h in older but not young rats. Both groups were impaired at 7 days. These findings support that not only aspects of general memory, but also context-dependent extinction learning, are affected by moderate aging. This may reflect less flexibility in

  11. Precompaction irradiation effects: Particles from an early active sun?

    NASA Technical Reports Server (NTRS)

    Caffee, M. W.; Goswami, J. N.; Hohenberg, C. M.; Swindle, T. D.

    1986-01-01

    Two recent studies have shown that solar flare irradiated grains from Murchison and Kapoeta have excess spallogenic Ne-21 compared to unirradiated grains, indicating large precompaction particle irradiation effects. The quantity of cosmogenic neon in these grains presents serious difficulties for either galactic cosmic ray or normal solar flare sources. In the first study it was suggested that the effect might be the result of exposure to an early active sun. The more recent experiment both confirms the earlier results and provides constraints on the characteristic energy spectrum on the irradiation. The first results were obtained from Murchison olivines and Kapoeta pyroxenes by mass spectrometric analysis of sets of grains selected on the basis of the presence or absence of solar flare particle tracks. In the second work plagioclase feldspar grains from Kapoeta were studied.

  12. Early Miocene Tectonic Activity in the western Ross Sea (Antarctica)

    NASA Astrophysics Data System (ADS)

    Sauli, C.; Sorlien, C. C.; Busetti, M.; Geletti, R.; De Santis, L.

    2012-12-01

    In the framework of the Rossmap Italian PNRA work objectives to compile extended and revised digital maps of the main unconformities in Ross Sea, Antarctica, much additional seismic reflection data, that were not available to previous ANTOSTRAT compilation, were incorporated into a new ROSSMAP interpretation. The correlation across almost all of Ross Sea, from DSDP Site 270 and Site 272 in Eastern Basin to northern Victoria Land Basin, of additional early Miocene and late Oligocene horizons that were not part of ANTOSTRAT allows interpretations to be made of fault activity and glacial erosion or deposition at a finer time resolution. New conclusions include that extensional or transtensional fault activity within the zone between Victoria Land Basin and Northern Basin, initiated by 23 Ma or earlier, and continued after 18 Ma. Steep parallel-striking faults in southern Victoria Land Basin display both reverse and normal separation of 17.5 Ma (from Cape Roberts Program-core 1) and post-16 Ma horizons, suggesting an important strike-slip component. This result may be compared with published papers that proposed post-17 Ma extension in southern Victoria Land Basin, 16-17 Ma extension in the AdareTrough, north of the Ross Sea continental shelf, but no Miocene extension affecting the Northern Basin (Granot et al., 2010). Thus, our evidence for extension through the early Miocene is significant to post-spreading tectonic models. Reference Granot R., Cande S. C., Stock J. M., Davey F. J. and Clayton R. W. (2010) Postspreading rifting in the Adare Basin, Antarctica: Regional tectonic consequences. Geochem. Geophys. Geosyst., 8, Q08005, doi:10.1029/2010GC003105.

  13. Early age damage quantification of actively restrained concrete using inverse analysis

    NASA Astrophysics Data System (ADS)

    Albanna, Ali

    Early-age cracking can be a significant problem in concrete pavements, floors, and bridge decks. Cracking occurs when the volumetric changes associated with drying, hydration, and temperature reduction are prevented. Good knowledge about the characteristics of early age concrete is necessary to achieve reliable crack control. Volumetric changes due to shrinkage depend on the type of concrete and its components. It has been found that light weight aggregates can work as internal reservoir to supply the concrete matrix with water that is needed during the early age; this process is called internal curing. Also fibers can give more ductility to the concrete and produce less shrinkage. There is a need to better understand the effects of early age uniaxial restraint on long term concrete mechanical performance. In this study, two types of concrete were studied (high performance fiber reinforced concrete and ordinary concrete) under actively restrained loading conditions to assess the effect on the long term fracture toughness and energy. Single edge notched specimens having dimensions of 250 mm x 150 mm x 75 mm and a notch to depth ratio of 0.33 were caste and used in both direct tension and three point bending. The direct tension tests were carried out on a direct tension loading frame constructed in house that was supplied with two mechanical jacks and load cell.

  14. 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

  15. An analytical method about anomalies on the synthetical variables of the multiple seismic activity parameters-taking 2 M =7 earthquakes occurring in Qinghai as examples

    NASA Astrophysics Data System (ADS)

    Ma, Heqing; Yang, Mingzhi

    2014-05-01

    Based on the random field theory, a new method of the synthetical variables of the multiple seismic activity parameters has been proposed. This method is that the natural perpendicular function development has been used on the random field function of seismic activity first. And then the synthetical variables constituted of the linear combination of four seismic activity parameters, i.e. the seismic strain release E-, the average distance between each two earthquakes D, the average time interval between each two earthquakes T , and the earthquake occurrence rate N have been studied. Though the analysis on the synthetical variables about the field, the seismic activity anomalies before large earthquakes have been drew. As the examples, the Gonghe M=7.0 earthquake occurred in Qinghai, 1990 and the Yushu M=7.1 earthquake occurred in Qinghai, 2010 have been discussed. The results have showed that before the two M=7 earthquakes, the main synthetical variables have all showed obvious abnormal variations, displaying better corresponding relationship with these two earthquakes. The synthetical variables of seismic activity field can focus on the slight differences which are included in each original variable. And the abnormal variations showed from the synthetical variables are as obvious as possible. The authors think that the synthetical variable method is possibly an effective analytic technique. Key words: seismic activity field; natural perpendicular function development; synthetical variables; anomaly; Earthquake example

  16. 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

  17. 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

  18. Constraints on transcriptional activator function contribute to transcriptional quiescence during early Xenopus embryogenesis.

    PubMed Central

    Almouzni, G; Wolffe, A P

    1995-01-01

    We have examined the cause of transcriptional quiescence prior to the mid-blastula transition (MBT) in Xenopus laevis. We have found distinct requirements for transcription of class II and class III genes. An artificial increase of the amount of DNA present within the embryo over that found at the MBT allows precocious transcription of tRNA genes, but not of the adenovirus E4 or human cytomegalovirus (CMV) promoters. Thus titration of an inhibitor by exogenous DNA determines class III but not class II gene activation. We demonstrate that the action of the inhibitor depends on the association of core histones with DNA. The addition of exogenous TBP, together with an increase in the amount of DNA within the embryo, allows significant basal transcription of class II genes prior to the MBT, whereas it does not increase transcription of tRNA genes. To examine the activation of transcription above basal levels, we used a defined minimal promoter containing five Gal4 binding sites and the activator Gal4-VP16. Precocious transcriptional activation is directed by Gal4-VP16 prior to the MBT, demonstrating that a functional transcriptional machinery exists at this early developmental stage. Furthermore, since this activation can occur in the absence of exogenous TBP or chromatin titration, a transcription factor that can penetrate chromatin is sufficient for recruitment of this machinery to a promoter. Our results support the hypothesis that the temporal regulation of transcription during early embryogenesis in Xenopus reflects not only a titration of inhibitors by DNA, but also a deficiency in the activity of transcriptional activators prior to the MBT. Images PMID:7737126

  19. Activity in early visual areas predicts interindividual differences in binocular rivalry dynamics

    PubMed Central

    Yamashiro, Hiroyuki; Mano, Hiroaki; Umeda, Masahiro; Higuchi, Toshihiro; Saiki, Jun

    2013-01-01

    When dissimilar images are presented to the two eyes, binocular rivalry (BR) occurs, and perception alternates spontaneously between the images. Although neural correlates of the oscillating perception during BR have been found in multiple sites along the visual pathway, the source of BR dynamics is unclear. Psychophysical and modeling studies suggest that both low- and high-level cortical processes underlie BR dynamics. Previous neuroimaging studies have demonstrated the involvement of high-level regions by showing that frontal and parietal cortices responded time locked to spontaneous perceptual alternation in BR. However, a potential contribution of early visual areas to BR dynamics has been overlooked, because these areas also responded to the physical stimulus alternation mimicking BR. In the present study, instead of focusing on activity during perceptual switches, we highlighted brain activity during suppression periods to investigate a potential link between activity in human early visual areas and BR dynamics. We used a strong interocular suppression paradigm called continuous flash suppression to suppress and fluctuate the visibility of a probe stimulus and measured retinotopic responses to the onset of the invisible probe using functional MRI. There were ∼130-fold differences in the median suppression durations across 12 subjects. The individual differences in suppression durations could be predicted by the amplitudes of the retinotopic activity in extrastriate visual areas (V3 and V4v) evoked by the invisible probe. Weaker responses were associated with longer suppression durations. These results demonstrate that retinotopic representations in early visual areas play a role in the dynamics of perceptual alternations during BR. PMID:24353304

  20. 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

  1. 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

  2. Early T cell activation: integrating biochemical, structural, and biophysical cues.

    PubMed

    Malissen, Bernard; Bongrand, Pierre

    2015-01-01

    T cells carry out the formidable task of identifying small numbers of foreign antigenic peptides rapidly and specifically against a very noisy environmental background of endogenous self-peptides. Early steps in T cell activation have thus fascinated biologists and are among the best-studied models of cell stimulation. This remarkable process, critical in adaptive immune responses, approaches and even seems to exceed the limitations set by the physical laws ruling molecular behavior. Despite the enormous amount of information concerning the nature of molecules involved in the T cell antigen receptor (TCR) signal transduction network, and the description of the nanoscale organization and real-time analysis of T cell responses, the general principles of information gathering and processing remain incompletely understood. Here we review currently accepted key data on TCR function, discuss the limitations of current research strategies, and suggest a novel model of TCR triggering and a few promising ways of going further into the integration of available data. PMID:25861978

  3. Hidden Active Galactic Nuclei in Early-type Galaxies

    NASA Astrophysics Data System (ADS)

    Paggi, Alessandro; Fabbiano, Giuseppina; Civano, Francesca; Pellegrini, Silvia; Elvis, Martin; Kim, Dong-Woo

    2016-06-01

    We present a stacking analysis of the complete sample of early-type galaxies (ETGs) in the Chandra COSMOS (C-COSMOS) survey, to explore the nature of the X-ray luminosity in the redshift and stellar luminosity ranges 0\\lt z\\lt 1.5 and {10}9\\lt {L}K/{L}ȯ \\lt {10}13. Using established scaling relations, we subtract the contribution of X-ray binary populations to estimate the combined emission of hot ISM and active galactic nuclei (AGNs). To discriminate between the relative importance of these two components, we (1) compare our results with the relation observed in the local universe {L}X,{gas}\\propto {L}K4.5 for hot gaseous halos emission in ETGs, and (2) evaluate the spectral signature of each stacked bin. We find two regimes where the non-stellar X-ray emission is hard, consistent with AGN emission. First, there is evidence of hard, absorbed X-ray emission in stacked bins including relatively high z (∼1.2) ETGs with average high X-ray luminosity ({L}X {- {LMXB}}≳ 6× {10}42 {{erg}} {{{s}}}-1). These luminosities are consistent with the presence of highly absorbed “hidden” AGNs in these ETGs, which are not visible in their optical–IR spectra and spectral energy distributions. Second, confirming the early indication from our C-COSMOS study of X-ray detected ETGs, we find significantly enhanced X-ray luminosity in lower stellar mass ETGs ({L}K≲ {10}11{L}ȯ ), relative to the local {L}X,{gas}\\propto {L}K4.5 relation. The stacked spectra of these ETGs also suggest X-ray emission harder than expected from gaseous hot halos. This emission is consistent with inefficient accretion {10}-5-{10}-4{\\dot{M}}{Edd} onto {M}{BH}∼ {10}6-{10}8 {M}ȯ .

  4. Early organ-specific endothelial activation during hemorrhagic shock and resuscitation.

    PubMed

    van Meurs, Matijs; Wulfert, Francis M; Knol, Ageeth J; De Haes, Ann; Houwertjes, Martin; Aarts, Leon P H J; Molema, Grietje

    2008-02-01

    Multiple organ dysfunction syndrome (MODS) is a complication of hemorrhagic shock (HS) and related to high morbidity and mortality. Interaction of activated neutrophils and endothelial cells is considered to play a prominent role in the pathophysiology of MODS. Insight in the nature and molecular basis of endothelial cell activation during HS can assist in identifying new rational targets for early therapeutic intervention. In this study, we examined the kinetics and organ specificity of endothelial cell activation in a mouse model of HS. Anesthetized male mice were subjected to controlled hemorrhage to a MAP of 30 mmHg. Mice were killed after 15, 30, 60, or 90 min of HS. After 90 min of hemorrhagic shock, a group of mice was resuscitated with 6% hydroxyethyl starch 130/0.4. Untreated mice and sham shock mice that underwent instrumentation and 90 min of anesthesia without shock served as controls. Gene expression levels of inflammatory endothelial cell activation (P-selectin, E-selectin, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1) and hypoxia-responsive genes (vascular endothelial growth factor and hypoxia-inducible factor 1alpha) were quantified in kidney, liver, lung, brain, and heart tissue by quantitative reverse-transcription-polymerase chain reaction. Furthermore, we examined a selection of these genes with regard to protein expression and localization using immunohistochemical analysis. Induction of inflammatory genes occurred early during HS and already before resuscitation. Expression of adhesion molecules was significantly induced in all organs, albeit to a different extent depending on the organ. Endothelial genes CD31 and VE-cadherin, which function in endothelial cell homeostasis and integrity, were not affected during the shock phase except for VE-cadherin in the liver, which showed increased mRNA levels. The rapid inflammatory activation was not paralleled by induction of hypoxia-responsive genes. This study demonstrated

  5. "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

  6. Kindergarten Children's Involvement in Early Literacy Activities: Perspectives from Europe.

    ERIC Educational Resources Information Center

    Shiel, Gerry

    2002-01-01

    Focuses on early childhood literacy education and the perspectives offered by some European presenters at the 12th European Conference on Reading. Describes an ego-based literacy simulation for at-risk preschoolers from Norway; an early literacy support program for at-risk beginning readers from Slovakia; and a pre-kindergarten children's…

  7. 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.

  8. 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... to this notice will be considered public records. Title of Collection: Race to the Top--Early... to the Top--Early Learning Challenge program is authorized by Sections 14005 and 14006, Division...

  9. Activation of the sonic hedgehog signaling pathway occurs in the CD133 positive cells of mouse liver cancer Hepa 1–6 cells

    PubMed Central

    Jeng, Kuo-Shyang; Sheen, I-Shyan; Jeng, Wen-Juei; Yu, Ming-Che; Hsiau, Hsin-I; Chang, Fang-Yu; Tsai, Hsin-Hua

    2013-01-01

    Background The important role of cancer stem cells in carcinogenesis has been emphasized in research. CD133+ cells have been mentioned as liver cancer stem cells in hepatocellular carcinoma (HCC). Some researchers have proposed that the sonic hedgehog (Shh) pathway contributes to hepatocarcinogenesis and that the pathway activation occurs mainly in cancer stem cells. We investigated whether the activation of the Shh pathway occurs in CD133+ cells from liver cancer. Materials and methods We used magnetic sorting to isolate CD133+ cells from mouse cancer Hepa 1–6 cells. To examine the clonogenicity, cell culture and soft agar colony formation assay were performed between CD133+ and CD133− cells. To study the activation of the Shh pathway, we examined the mRNA expressions of Shh, patched homolog 1 (Ptch-1), glioma-associated oncogene homolog 1 (Gli-1), and smoothened homolog (Smoh) by real-time polymerase chain reaction of both CD133+ and CD133− cells. Results The number (mean ± standard deviation) of colonies of CD133+ cells and CD133− cells was 1,031.0 ± 104.7 and 119.7 ± 17.6 respectively. This difference was statistically significant (P < 0.001). Their clonogenicity was 13.7% ± 1.4% and 1.6% ± 0.2% respectively with a statistically significant difference found (P < 0.001). CD133+ cells and CD133− cells were found to have statistically significant differences in Shh mRNA and Smoh mRNA (P = 0.005 and P = 0.043 respectively). Conclusion CD133+ Hepa 1–6 cells have a significantly higher colony proliferation and clonogenicity. The Shh pathway is activated in these cells that harbor stem cell features, with an underexpression of Shh mRNA and an overexpression of Smoh mRNA. Blockade of the Shh signaling pathway may be a potential therapeutic strategy for hepatocarcinogenesis. PMID:23950652

  10. 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

  11. 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. PMID:26209847

  12. Effects of synthetic and naturally occurring flavonoids on Na sup + , K sup + -ATPase: Aspects of the structure-activity relationship and action mechanism

    SciTech Connect

    Hirano, T.; Oka, K.; Akiba, M. )

    1989-01-01

    A comparative study was made of the effects of 15 synthetic and naturally occurring flavonoids on the hydrolytic activity of Na{sup +}, K{sup +} -adenosine triphosphatase (ATPase). Twelve of the flavonoids examined were mono-hydroxy or mono-methoxy derivatives. All inhibited Na{sup +}, K{sup +} -ATPase from dog kidney cortex when present at concentrations from 40-1000 {mu}M. Flavones possessing cyclohexyl instead of the phenyl group were the most potent with IC{sub 50} at 257-320 {mu}M. Structure-activity relationships were observed among the following mono-substituted flavones as: (i) 2-cyclohexyl-benzopyran-4-one {much gt} 2-phenyl-benzopyran-4-one; (ii) 2-cyclohexyl-7-hydroxybenzopyran-4-one {gt} 2-cyclohexyl-6-hydroxy-benzopyran-4-one {gt} 2-cyclohexyl-5-hydroxybenzopyran-4-one. Some flavonoids showing potent inhibitory activity were also examined for ouabain-displacement activity on human erythrocytes. Hardly and of the flavonoids were able to block ({sup 3}H) ouabain binding to erythrocytes. These results suggest that the mechanism by which flavonoid block Na{sup +}, K{sup +} -ATPase is not related to the cardiac glycoside-specific binding site(s) of this enzyme.

  13. The 'cleavage' activities of foot-and-mouth disease virus 2A site-directed mutants and naturally occurring '2A-like' sequences.

    PubMed

    Donnelly, M L; Hughes, L E; Luke, G; Mendoza, H; ten Dam, E; Gani, D; Ryan, M D

    2001-05-01

    The 2A/2B cleavage of aphtho- and cardiovirus 2A polyproteins is mediated by their 2A proteins 'cleaving' at their own C termini. We have analysed this activity using artificial reporter polyprotein systems comprising green fluorescent protein (GFP) linked via foot-and-mouth disease virus (FMDV) 2A to beta-glucuronidase (GUS) -- forming a single, long, open reading frame. Analysis of the distribution of radiolabel showed a high proportion of the in vitro translation products (approximately 90%) were in the form of the 'cleavage' products GUS and [GFP2A]. Alternative models have been proposed to account for the 'cleavage' activity: proteolysis by a host-cell proteinase, autoproteolysis or a translational effect. To investigate the mechanism of this cleavage event constructs encoding site-directed mutant and naturally occurring '2A-like' sequences were used to program in vitro translation systems and the gel profiles analysed. Analysis of site-directed mutant 2A sequences showed that 'cleavage' occurred in constructs in which all the candidate nucleophilic residues were substituted -- with the exception of aspartate-12. This residue is not, however, conserved amongst all functional '2A-like' sequences. '2A-like' sequences were identified within insect virus polyproteins, the NS34 protein of type C rotaviruses, repeated sequences in Trypanosoma spp. and a eubacterial alpha-glucosiduronasesequence(Thermatoga maritima aguA). All of the 2A-like sequences analysed were active (to various extents), other than the eubacterial alpha-glucosiduronase 2A-like sequence. This method of control of protein biogenesis may well not, therefore, be confined to members of the PICORNAVIRIDAE: Taken together, these data provide additional evidence that neither FMDV 2A nor '2A-like' sequences are autoproteolytic elements. PMID:11297677

  14. 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

  15. Activated eosinophils and interleukin 5 expression in early recurrence of Crohn's disease.

    PubMed Central

    Dubucquoi, S; Janin, A; Klein, O; Desreumaux, P; Quandalle, P; Cortot, A; Capron, M; Colombel, J F

    1995-01-01

    Endoscopic recurrences after radical surgery for Crohn's disease are useful for studying the pathogenesis of initial lesions of Crohn's disease. Factors predisposing to recurrence are poorly understood, but it has been shown that eosinophilic infiltration of the neoileum may occur within a few weeks of resection. The aim of this study was to compare, in nine patients having an ileocolectomy, the infiltration of eosinophils and their activation state in normal and diseased areas of the neoileum, three months after surgery. Tissue eosinophils were studied by histochemical methods and electron microscopy. Mucosal expression of interleukin 5 (IL 5), an important eosinophil activating factor was studied using in situ hybridisation. Sixty per cent of patients had endoscopic recurrence at three months. Eosinophil infiltration was more pronounced in diseased than in endoscopically normal areas and was associated with a high expression of IL 5 mRNA. Ultrastructural analysis showed features of eosinophil activation, but no cytotoxic lesions of surrounding inflammatory or epithelial cells. This study suggests that local synthesis of IL 5 associated with eosinophil activation in the tissues could participate in early mucosal damage in Crohn's disease. Images Figure 1 Figure 2 Figure 3 PMID:7557575

  16. 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…

  17. 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…

  18. Naturally occurring chemical carcinogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Natural products are chemicals found in nature which have unique pharmacological effects. Humans are exposed to many of these bioactive naturally occurring chemicals via the air breathed, the water drunk and the food eaten. Exposure also occurs in clinical settings. Naturally occurring chemicals ...

  19. 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…

  20. 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…

  1. 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…

  2. 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.

  3. The activation of the decapping enzyme DCP2 by DCP1 occurs on the EDC4 scaffold and involves a conserved loop in DCP1

    PubMed Central

    Chang, Chung-Te; Bercovich, Natalia; Loh, Belinda; Jonas, Stefanie; Izaurralde, Elisa

    2014-01-01

    The removal of the 5′-cap structure by the decapping enzyme DCP2 and its coactivator DCP1 shuts down translation and exposes the mRNA to 5′-to-3′ exonucleolytic degradation by XRN1. Although yeast DCP1 and DCP2 directly interact, an additional factor, EDC4, promotes DCP1–DCP2 association in metazoan. Here, we elucidate how the human proteins interact to assemble an active decapping complex and how decapped mRNAs are handed over to XRN1. We show that EDC4 serves as a scaffold for complex assembly, providing binding sites for DCP1, DCP2 and XRN1. DCP2 and XRN1 bind simultaneously to the EDC4 C-terminal domain through short linear motifs (SLiMs). Additionally, DCP1 and DCP2 form direct but weak interactions that are facilitated by EDC4. Mutational and functional studies indicate that the docking of DCP1 and DCP2 on the EDC4 scaffold is a critical step for mRNA decapping in vivo. They also revealed a crucial role for a conserved asparagine–arginine containing loop (the NR-loop) in the DCP1 EVH1 domain in DCP2 activation. Our data indicate that DCP2 activation by DCP1 occurs preferentially on the EDC4 scaffold, which may serve to couple DCP2 activation by DCP1 with 5′-to-3′ mRNA degradation by XRN1 in human cells. PMID:24510189

  4. 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…

  5. 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.

  6. 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

  7. Early olfactory-induced rhythmic limb activity in the newborn rat.

    PubMed

    Fady, J C; Jamon, M; Clarac, F

    1998-06-15

    Locomotor-like rhythmic movements without postural constraints were elicited in newborn rats aged from a few hours to five days, using an olfactory stimulus provided by bedding materials. The rats were held in a sling with the front and the hind legs hanging on each side. The step frequency increased between postnatal days 0 and 4 (P0-P4); the step period was around 1 s at P0 and decreased during the following days. This decrease was larger in the forelimbs (650 ms at P4) than in the hindlimbs (750 ms at P4) and was mainly due to a decrease in stance duration. Both ipsilateral and contralateral legs moved in an alternating pattern. Analysis of the regulation of this pattern when a 1:1 or a 1:2 inter-leg coordination (with double steps) occurred showed that both anterior and posterior locomotion pattern generators were coupled very early. Results are discussed in relation to the locomotor activities studied at this early stage of life in other behavioral situations (swimming and air stepping), and in relation to fictive locomotion induced in vitro. PMID:9693789

  8. 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

  9. Structure-activity studies of the carcinogenicities in the mouse and rat of some naturally occurring and synthetic alkenylbenzene derivatives related to safrole and estragole.

    PubMed

    Miller, E C; Swanson, A B; Phillips, D H; Fletcher, T L; Liem, A; Miller, J A

    1983-03-01

    Twenty-three naturally occurring and synthetic alkenylbenzene derivatives structurally related to the hepatocarcinogen safrole (1-allyl-3,4-methylenedioxybenzene) were assayed for their hepatocarcinogenicity in mice. Some of these compounds (safrole, estragole, eugenol, anethole, methyleugenol, myristicin, elemicin, and dill and parsley apiols) may be ingested in very small amounts by human as natural components of certain spices, essential oils, or vegetables. Estragole (1-allyl-4-methoxybenzene) and its proximate carcinogenic metabolite 1'-hydroxyestragole, previously shown to induce hepatic tumors when administered to male CD-1 mice only during the preweaning period, also induced hepatic tumors on administration for 12 months in the diet of female CD-1 mice. Eugenol (1-allyl-4-hydroxy-3-methoxybenzene) and anethole (trans-4-methoxy-1-propenylbenzene) were inactive in this assay; they were also inactive when administered i.p. during the preweaning period at total doses of up to 9.45 mumol/mouse to male CD-1 or C57BL/6 x C3H F1 (hereafter called B6C3F1) mice. Methyleugenol (1-ally-3,4-dimethoxybenzene) and its 1'-hydroxy metabolite had activities similar to those of estragole and its 1'-hydroxy metabolite for the induction of hepatic tumors in male B6C3F1 mice treated prior to weaning; 1-allyl-1'-hydroxy-4-methoxynaphthalene was somewhat less active. At the levels tested, myristicin (1-allyl-5-methoxy-3,4-methylenedioxybenzene), elemicin (1-allyl-3,4,5-trimethoxybenzene) and its 1'-hydroxy metabolite, dill apiol (1-allyl-2,3-dimethoxy-4,5-methylenedioxybenzene), parsley apiol (1-allyl-2,5-dimethoxy-3,4-methylenedioxybenzene), 1'-hydroxyallybenzene, 3'-hydroxyanethole, and benzyl and anisyl alcohols had no detectable activity for the initiation of hepatic tumors on administration to male mice prior to weaning. The acetylenic derivative 1'-hydroxy-2',3'-dehydroestragole was much more active than either 1'-hydroxysafrole or 1'-hydroxyestragole when administered to

  10. 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. PMID:24448559

  11. 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

  12. 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. PMID:18476702

  13. Tyrosine phosphorylation-dependent activation of phosphatidylinositide 3-kinase occurs upstream of Ca2+-signalling induced by Fcgamma receptor cross-linking in human neutrophils.

    PubMed Central

    Vossebeld, P J; Homburg, C H; Schweizer, R C; Ibarrola, I; Kessler, J; Koenderman, L; Roos, D; Verhoeven, A J

    1997-01-01

    The effect of wortmannin on IgG-receptor (FcgammaR)-mediated stimulation of human neutrophils was investigated. The Ca2+ influx induced by clustering of both Fcgamma receptors was inhibited by wortmannin, as was the release of Ca2+ from intracellular stores. Wortmannin also inhibited, with the same efficacy, the accumulation of Ins(1,4,5)P3 observed after FcgammaR stimulation, but did not affect the increase in Ins(1,4,5)P3 induced by the chemotactic peptide, formyl-methionine-leucine-phenylalanine. Because wortmannin is, in the concentrations used here, an inhibitor of PtdIns 3-kinase, these results suggested a role for PtdIns 3-kinase upstream of Ca2+ signalling, induced by FcgammaR cross-linking. Support for this notion was obtained by investigating the effect of another inhibitor of PtdIns 3-kinase, LY 294002, and by studying the kinetics of PtdIns 3-kinase activation. We found translocation of PtdIns 3-kinase to the plasma membrane and increased PtdIns 3-kinase activity in the membrane as soon as 5 s after FcgammaR cross-linking, even before the onset of the Ca2+ response. Moreover, the translocation of PtdIns 3-kinase to the plasma membrane was inhibited by co-cross-linking of either FcgammaRIIa and FcgammaRIIIb with the tyrosine phosphatase, CD45, indicating a requirement for protein tyrosine phosphorylation in the recruitment of PtdIns 3-kinase to the plasma membrane. Taken together, our results suggest a role for PtdIns 3-kinase in early signal transduction events after FcgammaR cross-linking in human neutrophils. PMID:9173906

  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. 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

  16. Platelet Antistaphylococcal Responses Occur through P2X1 and P2Y12 Receptor-Induced Activation and Kinocidin Release▿

    PubMed Central

    Trier, Darin A.; Gank, Kimberly D.; Kupferwasser, Deborah; Yount, Nannette Y.; French, William J.; Michelson, Alan D.; Kupferwasser, Leon I.; Xiong, Yan Q.; Bayer, Arnold S.; Yeaman, Michael R.

    2008-01-01

    Platelets (PLTs) act in antimicrobial host defense by releasing PLT microbicidal proteins (PMPs) or PLT kinocidins (PKs). Receptors mediating staphylocidal efficacy and PMP or PK release versus isogenic PMP-susceptible (ISP479C) and -resistant (ISP479R) Staphylococcus aureus strains were examined in vitro. Isolated PLTs were incubated with ISP479C or ISP479R (PLT/S. aureus ratio range, 1:1 to 10,000:1) in the presence or absence of a panel of PLT inhibitors, including P2X and P2Y receptor antagonists of increasingly narrow specificity, and PLT adhesion receptors (CD41, CD42b, and CD62P). PLT-to-S. aureus exposure ratios of ≥10:1 yielded significant reductions in the viability of both strains. Results from reversed-phase high-performance liquid chromatography indicated that staphylocidal PLT releasates contained PMPs and PKs. At ratios below 10:1, the PLT antistaphylococcal efficacy relative to the intrinsic S. aureus PMP-susceptible or -resistant phenotype diminished. Apyrase (an agent of ADP degradation), suramin (a general P2 receptor antagonist), pyridoxal 5′-phosphonucleotide derivative (a specific P2X1 antagonist), and cangrelor (a specific P2Y12 antagonist) mitigated the PLT staphylocidal response against both strains, correlating with reduced levels of PMP and PK release. Specific inhibition occurred in the presence and absence of homologous plasma. The antagonism of the thromboxane A2, cyclooxygenase-1/cyclooxygenase-2, or phospholipase C pathway or the hindrance of surface adhesion receptors failed to impede PLT anti-S. aureus responses. These results suggest a multifactorial PLT anti-S. aureus response mechanism involving (i) a PLT-to-S. aureus ratio sufficient for activation; (ii) the ensuing degranulation of PMPs, PKs, ADP, and/or ATP; (iii) the activation of P2X1/P2Y12 receptors on adjacent PLTs; and (iv) the recursive amplification of PMP and PK release from these PLTs. PMID:18824536

  17. 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

  18. The Early Childhood Mental Health Best Practices Project. Report on Project Activities, Year Two.

    ERIC Educational Resources Information Center

    Multnomah County Dept. of Community and Family Services, Portland, OR. Behavioral Health Div.

    The goal of the Early Childhood Mental Health (ECMH) Best Practices Project in Multnomah County, Oregon, is to improve the ability of early childhood professionals and partners to support and strengthen the emotional and relational development of young children with their families and communities. This report presents the activities for Year 2 of…

  19. Rationale and Activities of Project on Television in Early Education: Progress Report, July - December 1975.

    ERIC Educational Resources Information Center

    Smart, Margaret E.; Williams, Frederick

    This progress report discusses the rationale and activities of the Project on Television in Early Childhood Education at the University of Southern California. Since January 1975, the Annenberg School and the School for Early Childhood Education have cooperated in a program of faculty and student interaction and informal research projects aimed at…

  20. 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…

  1. 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

  2. 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

  3. Early agr activation correlates with vancomycin treatment failure in multi-clonotype MRSA endovascular infections

    PubMed Central

    Abdelhady, Wessam; Chen, Liang; Bayer, Arnold S.; Seidl, Kati; Yeaman, Michael R.; Kreiswirth, Barry N.; Xiong, Yan Q.

    2015-01-01

    Objectives Persistent MRSA infections are especially relevant to endovascular infections and correlate with suboptimal outcomes. However, the virulence signatures of Staphylococcus aureus that drive such persistence outcomes are not well defined. In the current study, we investigated correlations between accessory gene regulator (agr) activation and the outcome of vancomycin treatment in an experimental model of infective endocarditis (IE) due to MRSA strains with different agr and clonal complex (CC) types. Methods Twelve isolates with the four most common MRSA CC and agr types (CC5-agr II, CC8-agr I, CC30-agr III and CC45-agr I) were evaluated for heterogeneous vancomycin-intermediate S. aureus (hVISA), agr function, agrA and RNAIII transcription, agr locus sequences, virulence and response to vancomycin in the IE model. Results Early agr RNAIII activation (beginning at 2 h of growth) in parallel with strong δ-haemolysin production correlated with persistent outcomes in the IE model following vancomycin therapy. Importantly, such treatment failures occurred across the range of CC/agr types studied. In addition, these MRSA strains: (i) were vancomycin susceptible in vitro; (ii) were not hVISA or vancomycin tolerant; and (iii) did not evolve hVISA phenotypes or perturbed δ-haemolysin activity in vivo following vancomycin therapy. Moreover, agr locus sequence analyses revealed no common point mutations that correlated with either temporal RNAIII transcription or vancomycin treatment outcomes, encompassing different CC and agr types. Conclusions These data suggest that temporal agr RNAIII activation and agr functional profiles may be useful biomarkers to predict the in vivo persistence of endovascular MRSA infections despite vancomycin therapy. PMID:25564565

  4. 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

  5. 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

  6. Active touch in late-preterm and early-term neonates.

    PubMed

    Molina, Michèle; Sann, Coralie; David, Morgane; Touré, Yacine; Guillois, Bernard; Jouen, François

    2015-04-01

    An infant-controlled tactile habituation without visual control procedure was used to evaluate the ability of 32 late-preterm neonates (mean gestational age: 34 weeks) and 32 early-term neonates (mean gestational age: 38 weeks) to actively explore with hands objects varying in texture (smooth, granular). Holding time and Hand Pressure Frequency (HPF) were recorded. Holding time decreased as habituation progressed in both group of neonates. Holding time increased from habituation trials to test trials only in early-term neonates. A reaction to novelty was only observed in early-term neonates. During habituation, HPF remained unchanged in late-preterm infants whereas HPF decreased in early-term infants. HPF increased from habituation trials to test trials in early-term neonates and in late-preterm infants. However, reaction to novelty was only observed for early-term infants. The significance of these results is discussed in reference to brain maturation in preterm infants. PMID:25783450

  7. The Predominance of Literacy Activities in Urban Early Childhood Education

    ERIC Educational Resources Information Center

    Liu, Daoying; Channell, Linda

    2015-01-01

    The purpose of this paper is to explore the predominance of literacy activities within the homes of African American toddlers in an urban setting in Mississippi. The data were collected through a Likert survey from parent participants in daycares, preschools, and churches, as well as institutions from five different parts of Jackson, MS. The…

  8. 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…

  9. Early activation defects in T lymphocytes from aged mice.

    PubMed

    Miller, R A; Garcia, G; Kirk, C J; Witkowski, J M

    1997-12-01

    Aging affects both calcium signals and protein kinase cascades in mouse T lymphocytes. The decline in calcium signal development largely represents differences between naive and memory T cells; the latter are resistant to increases in calcium concentration, and are more common in aged mice. Aging leads to declines in phosphorylation of a wide range of substrates in T cells stimulated by either anti-CD3 antibodies or by substances, such as phorbol myristate acetate (PMA) or ionomycin, that act at intracellular sites, but some phosphoproteins respond only in old T cells, and others respond regardless of age. Tyrosine phosphorylation of the CD3 zeta chain declines with age, both in resting T cells and after activation, but the proportion of Zap-70 that is bound to CD3 zeta increases in T cells from old mice. Zap-70 function and phosphorylation of CD3 zeta-associated Zap-70 change only slightly after stimulation of T cells by anti-CD3 and anti-CD4, and are at similar levels in activated old and young T cells. Nonetheless, induction of Raf-1, MEK, and ERK kinase activity declines with age in CD4 T cells. The effect of aging on T-cell activation is not simply an overall decline in signal intensity, but a set of qualitative changes that differ among subsets and depend at least partly on the nature of the stimulus. PMID:9476667

  10. 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

  11. Early network activity propagates bidirectionally between hippocampus and cortex.

    PubMed

    Barger, Zeke; Easton, Curtis R; Neuzil, Kevin E; Moody, William J

    2016-06-01

    Spontaneous activity in the developing brain helps refine neuronal connections before the arrival of sensory-driven neuronal activity. In mouse neocortex during the first postnatal week, waves of spontaneous activity originating from pacemaker regions in the septal nucleus and piriform cortex propagate through the neocortex. Using high-speed Ca(2+) imaging to resolve the spatiotemporal dynamics of wave propagation in parasagittal mouse brain slices, we show that the hippocampus can act as an additional source of neocortical waves. Some waves that originate in the hippocampus remain restricted to that structure, while others pause at the hippocampus-neocortex boundary and then propagate into the neocortex. Blocking GABAergic neurotransmission decreases the likelihood of wave propagation into neocortex, whereas blocking glutamatergic neurotransmission eliminates spontaneous and evoked hippocampal waves. A subset of hippocampal and cortical waves trigger Ca(2+) waves in astrocytic networks after a brief delay. Hippocampal waves accompanied by Ca(2+) elevation in astrocytes are more likely to propagate into the neocortex. Finally, we show that two structures in our preparation that initiate waves-the hippocampus and the piriform cortex-can be electrically stimulated to initiate propagating waves at lower thresholds than the neocortex, indicating that the intrinsic circuit properties of those regions are responsible for their pacemaker function. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 661-672, 2016. PMID:26385616

  12. 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. PMID:25996659

  13. Early contacts between T lymphocytes and activating surfaces

    NASA Astrophysics Data System (ADS)

    Cretel, E.; Touchard, D.; Benoliel, A. M.; Bongrand, P.; Pierres, A.

    2010-05-01

    Cells continually probe their environment to adapt their behaviour. A current challenge is to determine how they analyse nearby surfaces and how they process information to take decisions. We addressed this problem by monitoring human T lymphocyte attachment to surfaces coated with activating anti-CD3 or control anti-HLA antibodies. Interference reflection microscopy allowed us to monitor cell-to-surface apposition with a few nanometre vertical resolution during the first minutes following contact. We found that (i) when a cell fell on a surface, contact extension was preceded by a lag of several tens of seconds. (ii) During this lag, vertical membrane undulations seemed to generate transient contacts with underlying surfaces. (iii) After the lag period, the contact area started increasing linearly with a rate of about 1.5 µm2 s - 1 on activating surfaces and about 0.2 µm2 s - 1 on control surfaces. (iv) Concomitantly with lateral surface extension, the apparent distance between cell membranes and surfaces steadily decreased. These results are consistent with the hypothesis that the cell decision to spread rapidly on activating surfaces resulted from the integration of information yielded by transient contacts with these surfaces generated by membrane undulations during a period of about 1 min.

  14. 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

  15. 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.

  16. 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.

  17. Peroxiredoxin1 Prevents Excessive Endothelial Activation and Early Atherosclerosis

    PubMed Central

    Kisucka, Janka; Chauhan, Anil K.; Patten, Ian S.; Yesilaltay, Ayce; Neumann, Carola; Van Etten, Richard A.; Krieger, Monty; Wagner, Denisa D.

    2016-01-01

    The peroxiredoxin (Prdx) family of antioxidant enzymes uses redox-active cysteines to reduce peroxides, lipid hydroperoxides, and peroxynitrites. Prdx1 is known to be important to protect red blood cells against reactive oxygen species and in tumor prevention. In this study, the role of Prdx1 in inflammation, thrombosis, and atherosclerosis was investigated. Using intravital microscopy, we showed that the number of leukocytes rolling per minute in unstimulated veins was increased by 2.5-fold in Prdx1−/− compared to Prdx1+/+ mice. In Prdx1−/− mice, 50% of leukocytes rolled at a velocity <10 μm/sec compared with 10% in Prdx1+/+ mice, suggesting that adhesion molecule density on the endothelium may have been increased by Prdx1 deficiency. Indeed, endothelial P-selectin, soluble P-selectin, and von Willebrand factor in plasma were increased in Prdx1−/− mice compared to Prdx1+/+ mice, indicating elevated Weibel–Palade body release. In contrast to this excessive endothelial activation, Prdx1−/− platelets showed no sign of hyperreactivity, and their aggregation both in vitro and in vivo was normal. We also examined the role of Prdx1 in the apoE−/− murine spontaneous model of atherosclerosis. Prdx1−/−/apoE−/− mice fed normal chow developed larger, more macrophage-rich aortic sinus lesions than Prdx1+/+/apoE−/− mice, despite similar amounts and size distributions of cholesterol in their plasma lipoproteins. Thus, Prdx1 protects against excessive endothelial activation and atherosclerosis, and the Prdx1−/− mice could serve as an animal model susceptible to chronic inflammation. PMID:18689572

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

    PubMed

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

    2014-08-29

    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:25185030

  19. 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

  20. The evolution and orientation of early cycle 22 active regions

    NASA Technical Reports Server (NTRS)

    Cannon, Anne T.; Marquette, William H.

    1991-01-01

    The evolution of six major active regions which appeared during the first phase of the present solar cycle (cycle 22) has been studied. It was found that the northern hemisphere regions exhibited a broad range of evolutionary behavior in which the commonly accepted 'normal pattern' (whereby the follower flux moves preferentially polewards ahead of the leader flux) is represented at one end of the range. At the other end of the range, the leader flux is displaced polewards of the follower flux. In the latter cases equatorward extensions of the polar coronal hole are noted.

  1. "Rollbahn mord": the early activities of Einsatzgruppe C.

    PubMed

    Lozowick, Y

    1987-01-01

    Einsatzgruppe C was active in the Ukraine and became responsible for the murder of Jews, including the Babi-Yar massacre at Kiev. At first, men only were murdered, but after a number of weeks, women and children became victims, too. The Einsatzgruppe was assisted in its task by the Wehrmacht, the German police, other units of the SS and by both individuals and organized groups of local Ukrainians and Germans. Though no clear orders regarding the scope of the Final Solution seem to have been given, Einsatzgruppe C relentlessly continued pursuing its victims until the act of murder itself became routine. PMID:11617156

  2. 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.

  3. 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

  4. 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…

  5. 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…

  6. 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.…

  7. 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…

  8. 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…

  9. 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…

  10. 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.

  11. Aberrant early visual neural activity and brain-behavior relationships in anorexia nervosa and body dysmorphic disorder

    PubMed Central

    Li, Wei; Lai, Tsz M.; Loo, Sandra K.; Strober, Michael; Mohammad-Rezazadeh, Iman; Khalsa, Sahib; Feusner, Jamie

    2015-01-01

    Background: Body dysmorphic disorder (BDD) and anorexia nervosa (AN) share the clinical symptom of disturbed body image, which may be a function of perceptual distortions. Previous studies suggest visual or visuospatial processing abnormalities may be contributory, but have been unable to discern whether these occur early or late in the visual processing stream. We used electroencephalography (EEG) and visual event related potentials (ERP) to investigate early perceptual neural activity associated with processing visual stimuli. Methods: We performed EEG on 20 AN, 20 BDD, 20 healthy controls, all unmedicated. In order to probe configural/holistic and detailed processing, participants viewed photographs of faces and houses that were unaltered or filtered to low or high spatial frequencies, respectively. We calculated the early ERP components P100 and N170, and compared amplitudes and latencies among groups. Results: P100 amplitudes were smaller in AN than BDD and healthy controls, regardless of spatial frequency or stimulus type (faces or houses). Similarly, N170 latencies were longer in AN than healthy controls, regardless of spatial frequency or stimulus type, with a similar pattern in BDD at trend level significance. N170 amplitudes were smaller in AN than controls for high and normal spatial frequency images, and smaller in BDD than controls for normal spatial frequency images, regardless of stimulus type. Poor insight correlated with lower N170 amplitudes for normal and low spatial frequency faces in the BDD group. Conclusions: Individuals with AN exhibit abnormal early visual system activity, consistent with reduced configural processing and enhanced detailed processing. This is evident regardless of whether the stimuli are appearance–or non-appearance-related, and thus may be a reflection of general, early perceptual abnormalities. As N170 amplitude could be a marker of structural encoding of faces, lower values may be associated with perceptual distortions

  12. 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 ...

  13. 12 CFR 408.4 - Early involvement in foreign activities for which Eximbank financing may be requested.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 5 2014-01-01 2014-01-01 false Early involvement in foreign activities for... Implementing Procedures § 408.4 Early involvement in foreign activities for which Eximbank financing may be requested. (a) Section 1501.2(d) of the NEPA Regulations requires agencies to provide for early...

  14. 12 CFR 408.4 - Early involvement in foreign activities for which Eximbank financing may be requested.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 5 2013-01-01 2013-01-01 false Early involvement in foreign activities for... Implementing Procedures § 408.4 Early involvement in foreign activities for which Eximbank financing may be requested. (a) Section 1501.2(d) of the NEPA Regulations requires agencies to provide for early...

  15. 12 CFR 408.4 - Early involvement in foreign activities for which Eximbank financing may be requested.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 5 2012-01-01 2012-01-01 false Early involvement in foreign activities for... Implementing Procedures § 408.4 Early involvement in foreign activities for which Eximbank financing may be requested. (a) Section 1501.2(d) of the NEPA Regulations requires agencies to provide for early...

  16. 12 CFR 408.4 - Early involvement in foreign activities for which Eximbank financing may be requested.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 4 2011-01-01 2011-01-01 false Early involvement in foreign activities for... Implementing Procedures § 408.4 Early involvement in foreign activities for which Eximbank financing may be requested. (a) Section 1501.2(d) of the NEPA Regulations requires agencies to provide for early...

  17. 12 CFR 408.4 - Early involvement in foreign activities for which Eximbank financing may be requested.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Early involvement in foreign activities for... Implementing Procedures § 408.4 Early involvement in foreign activities for which Eximbank financing may be requested. (a) Section 1501.2(d) of the NEPA Regulations requires agencies to provide for early...

  18. Posttranslational regulation of nitrogenase activity in Azospirillum brasilense ntrBC mutants: ammonium and anaerobic switch-off occurs through independent signal transduction pathways.

    PubMed Central

    Zhang, Y; Burris, R H; Ludden, P W; Roberts, G P

    1994-01-01

    Nitrogenase activity is regulated by reversible ADP-ribosylation in response to NH4+ and anaerobic conditions in Azospirillum brasilense. The effect of mutations in ntrBC on this regulation was examined. While NH4+ addition to ntrBC mutants caused a partial loss of nitrogenase activity, the effect was substantially smaller than that seen in ntr+ strains. In contrast, nitrogenase activity in these mutants was normally regulated in response to anaerobic conditions. The analysis of mutants lacking both the ntrBC gene products and dinitrogenase reductase activating glycohydrolase (DRAG) suggested that the primary effect of the ntrBC mutations was to alter the regulation of DRAG activity. Although nif expression in the ntr mutants appeared normal, as judged by activity, glutamine synthetase activity was significantly lower in ntrBC mutants than in the wild type. We hypothesize that this lower glutamine synthetase activity may delay the transduction of the NH4+ signal necessary for the inactivation of DRAG, resulting in a reduced response of nitrogenase activity to NH4+. Finally, data presented here suggest that different environmental stimuli use independent signal pathways to affect this reversible ADP-ribosylation system. Images PMID:7916012

  19. 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.

  20. 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

  1. 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.

  2. 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

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

    PubMed

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

    2015-08-01

    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

  4. Naturally occurring cardiac glycosides.

    PubMed

    Radford, D J; Gillies, A D; Hinds, J A; Duffy, P

    1986-05-12

    Cardiac glycoside poisoning from the ingestion of plants, particularly of oleanders, occurs with reasonable frequency in tropical and subtropical areas. We have assessed a variety of plant specimens for their cardiac glycoside content by means of radioimmunoassays with antibodies that differ in their specificity for cardiac glycosides. Significant amounts of immunoreactive cardiac glycoside were found to be present in the ornamental shrubs: yellow oleander (Thevetia peruviana); oleander (Nerium oleander); wintersweet (Carissa spectabilis); bushman's poison (Carissa acokanthera); sea-mango (Cerbera manghas); and frangipani (Plumeria rubra); and in the milkweeds: redheaded cotton-bush (Asclepias curassavica); balloon cotton (Asclepias fruiticosa); king's crown (Calotropis procera); and rubber vine (Cryptostegia grandifolia). The venom gland of the cane toad (Bufo marinus) also contained large quantities of cardiac glycosides. The competitive immunoassay method permits the rapid screening of specimens that are suspected to contain cardiac glycosides. Awareness of the existence of these plant and animal toxins and their dangers allows them to be avoided and poisoning prevented. The method is also useful for the confirmation of the presence of cardiac glycosides in serum in cases of poisoning. PMID:3086679

  5. 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

  6. Influence of early pH decline on calpain activity in porcine muscle.

    PubMed

    Pomponio, Luigi; Ertbjerg, Per; Karlsson, Anders H; Costa, Leonardo Nanni; Lametsch, René

    2010-05-01

    This study investigated the influence of post-mortem pH decline on calpain activity and myofibrillar degradation. From 80 pigs, 30 Longissimus dorsi (LD) muscles were selected on the basis of pH values at 3h post-mortem and classified into groups of 10 as fast, intermediate and slow pH decline. The rate of pH decline early post-mortem differed between the three groups, but the ultimate pH values were similar at 24h. Calpain activity and autolysis from 1 to 72h post-mortem were determined using casein zymography and studied in relation to myofibrillar fragmentation. Colour and drip loss were measured. A faster decrease in pH resulted in reduced level of mu-calpain activity and increased autolysis of the enzyme, and hence an earlier loss of activity due to activation of mu-calpain in muscles with a fast pH decline. Paralleling the mu-calpain activation in muscles with a fast pH decline a higher myofibril fragmentation at 24h post-mortem was observed, which was no longer evident in the later phase of the tenderization process. In conclusion, the rate of early pH decline influenced mu-calpain activity and the rate but not the extent of myofibrillar degradation, suggesting an early effect of proteolysis on myofibril fragmentation that is reduced during ageing due to an earlier exhaustion of mu-calpain activity. PMID:20374873

  7. 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.

  8. Accumulation of Advanced Glycation End-Products and Activation of the SCAP/SREBP Lipogenetic Pathway Occur in Diet-Induced Obese Mouse Skeletal Muscle

    PubMed Central

    Mastrocola, Raffaella; Collino, Massimo; Nigro, Debora; Chiazza, Fausto; D’Antona, Giuseppe; Aragno, Manuela; Minetto, Marco A.

    2015-01-01

    Aim of this study was to investigate whether advanced glycation end-products (AGEs) accumulate in skeletal myofibers of two different animal models of diabesity and whether this accumulation could be associated to myosteatosis. Male C57Bl/6j mice and leptin-deficient ob/ob mice were divided into three groups and underwent 15 weeks of dietary manipulation: standard diet-fed C57 group (C57, n = 10), high-fat high-sugar diet-fed C57 group (HFHS, n = 10), and standard diet-fed ob/ob group (OB/OB, n = 8). HFHS mice and OB/OB mice developed glycometabolic abnormalities in association with decreased mass of the gastrocnemius muscle, fast-to-slow transition of muscle fibers, and lipid accumulation (that occurred preferentially in slow compared to fast fibers). Moreover, we found in muscle fibers of HFHS and OB/OB mice accumulation of AGEs that was preferential for the lipid-accumulating cells, increased expression of the lipogenic pathway SCAP/SREBP, and co-localisation between AGEs and SCAP-(hyper)expressing cells (suggestive for SCAP glycosylation). The increased expression of the SCAP/SREBP lipogenic pathway in muscle fibers is a possible mechanism underlying lipid accumulation and linking myosteatosis to muscle fiber atrophy and fast-to-slow transition that occur in response to diabesity. PMID:25750996

  9. 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.

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

    PubMed Central

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

    2015-01-01

    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 = 2.6 µM). 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 flavanoids 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. PMID:25650313

  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. Effects of early-onset voluntary exercise on adult physical activity and associated phenotypes in mice.

    PubMed

    Acosta, Wendy; Meek, Thomas H; Schutz, Heidi; Dlugosz, Elizabeth M; Vu, Kim T; Garland, Theodore

    2015-10-01

    The purpose of this study was to evaluate the effects of early-life exercise on adult physical activity (wheel running, home-cage activity), body mass, food consumption, and circulating leptin levels in males from four replicate lines of mice selectively bred for high voluntary wheel running (High Runner or HR) and their four non-selected control (C) lines. Half of the mice were given wheel access shortly after weaning for three consecutive weeks. Wheel access was then removed for 52 days, followed by two weeks of adult wheel access for all mice. A blood sample taken prior to adult wheel testing was analyzed for circulating leptin concentration. Early-life wheel access significantly increased adult voluntary exercise on wheels during the first week of the second period of wheel access, for both HR and C mice, and HR ran more than C mice. During this same time period, activity in the home cages was not affected by early-age wheel access, and did not differ statistically between HR and C mice. Throughout the study, all mice with early wheel access had lower body masses than their sedentary counterparts, and HR mice had lower body masses than C mice. With wheel access, HR mice also ate significantly more than C mice. Early-life wheel access increased plasma leptin levels (adjusted statistically for fat-pad mass as a covariate) in C mice, but decreased them in HR mice. At sacrifice, early-life exercise had no statistically significant effects on visceral fat pad, heart (ventricle), liver or spleen masses (all adjusted statistically for variation in body mass). Results support the hypothesis that early-age exercise in mice can have at least transitory positive effects on adult levels of voluntary exercise, in addition to reducing body mass, and may be relevant for the public policy debates concerning the importance of physical education for children. PMID:26079567

  13. 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

  14. PHYSICAL EFFECTS OCCURRING DURING GENERATION AND AMPLIFICATION OF LASER RADIATION: Kinetic model of the active medium of an XeCl laser pumped by an electron beam

    NASA Astrophysics Data System (ADS)

    Boĭchenko, A. M.; Derzhiev, V. I.; Zhidkov, A. G.; Yakovlenko, Sergei I.

    1989-02-01

    Kinetic models of active media of an XeCl laser are developed for the case when these media are diluted by various buffer gases (helium, neon, argon) and the laser is pumped by an electron beam. The results of the calculations are in satisfactory agreement with experimental data.

  15. Antiplasmodial, cytotoxic activities and characterization of a new naturally occurring quinone methide pentacyclic triterpenoid derivative isolated from Salacia leptoclada Tul. (Celastraceae) originated from Madagascar

    PubMed Central

    Ruphin, Fatiany Pierre; Baholy, Robijaona; Emmanue, Andrianarivo; Amelie, Raharisololalao; Martin, Marie-Therese; Koto-te-Nyiwa, Ngbolua

    2013-01-01

    Objective To validate scientifically the traditional use of Salacia leptoclada Tul. (Celastraceae) (S. leptoclada) and to isolate and elucidate the structure of the biologically active compound. Methods Bioassay-guided fractionation of the acetonic extract of the stem barks of S. leptoclada was carried out by a combination of chromatography technique and biological experiments in viro using Plasmodium falciparum and P388 leukemia cell lines as models. The structure of the biologically active pure compound was elucidated by 1D and 2D NMR spectroscopy and mass spectrometry. Results Biological screening of S. leptoclada extracts resulted in the isolation of a pentacyclic triterpenic quinone methide. The pure compound exhibited both in vitro a cytotoxic effect on murine P388 leukemia cells with IC50 value of (0.041±0.020) µg/mL and an antiplasmodial activity against the chloroquine-resistant strain FC29 of Plasmodium falciparum with an IC50 value of (0.052±0.030) µg/mL. Despite this interesting anti-malarial property of the lead compound, the therapeutic index was weak (0.788). In the best of our knowledge, the quinone methide pentacyclic triterpenoid derivative compound is reported for the first time in S. leptoclada. Conclusions The results suggest that furthers studies involving antineoplastic activity is needed for the development of this lead compound as anticancer drug. PMID:24075342

  16. 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.

  17. Early Maritime Activity on the Dead Sea: Bitumen Harvesting and the Possible Use of Reed Watercraft

    NASA Astrophysics Data System (ADS)

    Oron, Asaf; Galili, Ehud; Hadas, Gideon; Klein, Micha

    2015-04-01

    Most studies of ancient maritime activity on the Dead Sea focus on the Hellenistic to the Early Byzantine periods, for which a rich body of archaeological and historic data exists. However, finds of Dead Sea bitumen at distant prehistoric sites and an anchor dating to the seventh century BC indicate that maritime activity on the lake preceded the Greek and Roman periods, and raise questions regarding this activity's origins and nature. By linking the exploitation of Dead Sea bitumen with the use of watercraft, and through consideration of a broader early maritime record of the ancient Near East, this study pushes back the dating of this activity on the lake and suggests the nature of its watercraft.

  18. Activating Na+-K+ ATPase: a potential cardioprotective therapy during early hemorrhagic shock.

    PubMed

    Li, Weijing; Wang, Xuanlin; He, Min; Wang, Chunyan; Qiao, Zhixin; Wang, Qingjun; Ren, Suping; Yu, Qun

    2014-12-01

    Cell volume and resting potential are heavily affected by the activity of Na+-K+ ATPase (NKA, Na+-K+ pump), an essential membrane protein that regulates plasma K+ and Na+ levels. It is generally accepted that the ineffective perfusion of body tissues inhibits NKA activity and that NKA activity and heart failure are closely related. Recently, research has proven that the activation of NKA provides significant cardioprotection against ischemic injury. Based on these data, we propose that NKA stimulation could attenuate the development of heart arrhythmia during the early phase of hemorrhagic shock. PMID:25459134

  19. 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…

  20. 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.)…

  1. 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…

  2. 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

    ... in response to this notice will be considered public records. Title of Collection: Evaluation of the... Agency Information Collection Activities; Comment Request; Evaluation of the Early Warning and Intervention Monitoring System AGENCY: Institute of Education Sciences/National Center for Education...

  3. 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…

  4. 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…

  5. 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…

  6. 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…

  7. 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…

  8. 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…

  9. 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)…

  10. 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.

  11. 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…

  12. 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…

  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. 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…

  15. 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:…

  16. Early kinetic window of target T cell susceptibility to CD25+ regulatory T cell activity.

    PubMed

    Sojka, Dorothy K; Hughson, Angela; Sukiennicki, Teresa L; Fowell, Deborah J

    2005-12-01

    Peripheral tolerance is maintained in part by thymically derived CD25+CD4+ T cells (regulatory T cells (Tregs)). Their mechanism of action has not been well characterized. Therefore, to get a better understanding of Treg action, we investigated the kinetics of murine Treg activity in vitro. Tregs were suppressive within a surprisingly narrow kinetic window: necessary and sufficient only in the first 6-10 h of culture. Visualization of this time frame, using a sensitive single-cell assay for IL-2, revealed the early elaboration of target cell IL-2 producers in the first 6 h despite the presence of CD25+CD4+ Tregs. However, after 6 h, a rapid rise in the number of IL-2 producers in the absence of Tregs was dramatically abrogated by the presence of Tregs. Importantly, the timing of suppression was dictated by the kinetics of target T cell activation suggesting that early target T cell signals may alter susceptibility to suppression. Modulating target T cell activation signals with provision of CD28, IL-2, or high Ag dose all abrogated suppression of proliferation late in culture. However, only CD28 signals enabled target T cells to resist the early Treg-induced down-regulation of IL-2. Therefore the quality of early target T cell activation signals, in particular engagement of CD28, represents an important control point in the balance between vulnerability and resistance to Treg suppression. PMID:16301632

  17. 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…

  18. 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

  19. Human and rat hepatocyte toxicity and protein phosphatase 1 and 2A inhibitory activity of naturally occurring desmethyl-microcystins and nodularins.

    PubMed

    Ufelmann, Helena; Krüger, Thomas; Luckas, Bernd; Schrenk, Dieter

    2012-03-11

    Contamination of water, foods and food supplements by various genera of cyanobacteria is a serious health problem worldwide for humans and animals, largely due to the toxic effects of microcystins (MCs) and nodularin (NOD), a group of hepatotoxic cyclic peptides. The toxins occur in variable structures resulting in more than 90 different MCs and 8 different NODs, many of them not having been investigated for their toxic potency. Potent MCs such as MC-LR have been shown to elicit their hepatotoxic potency via inhibition of hepatic protein phosphatases (PP) 1 and 2A leading to over-phosphorylation of vital cellular proteins. This mechanism of action is also thought to be responsible for the long term tumor promoting action of certain MCs and NOD in the liver. Here, we report on the isolation of certain MCs and NOD as well as a number of their desmethylated derivatives from algae bloom. Subsequently, we determined the cytotoxicity of these compounds in isolated primary human and rat hepatocytes in culture. In parallel experiments, we analyzed the inhibitory potency of these congeners on PP1 and 2A using commercially available enzymes. We found in primary rat hepatocytes that MC-LR, -YR and NOD were cytotoxic, namely in the 10 to >50 nM range, while MC-RR was not. The desmethylated congeners of MC-LR, -YR, and NOD were equally or more-toxic as/than their fully methylated counterparts. In primary human hepatocytes we could show that MC-LR, NOD and the desmethylated variants [³Asp]MC-LR, [⁷Dha]MC-LR and [¹Asp]NOD were cytotoxic in the 20 to >600 nM range. Inhibition data with human, bovine and rabbit protein phosphatases 1 and 2A were roughly in accordance with the cytotoxicity findings in human and rat hepatocytes, i.e. desmethylation had no pronounced effects on the inhibitory potencies. Thus, a variety of naturally occurring desmethylated MC and NOD congeners have to be considered as being at least as toxic as the corresponding fully methylated derivatives. PMID

  20. 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

  1. A naturally occurring nonapeptide functionally compensates for the CP1 domain of leucyl-tRNA synthetase to modulate aminoacylation activity.

    PubMed

    Tan, Min; Yan, Wei; Liu, Ru-Juan; Wang, Meng; Chen, Xin; Zhou, Xiao-Long; Wang, En-Duo

    2012-04-15

    aaRSs (aminoacyl-tRNA synthetases) establish the rules of the genetic code by catalysing the formation of aminoacyl-tRNA. The quality control for aminoacylation is achieved by editing activity, which is usually carried out by a discrete editing domain. For LeuRS (leucyl-tRNA synthetase), the CP1 (connective peptide 1) domain is the editing domain responsible for hydrolysing mischarged tRNA. The CP1 domain is universally present in LeuRSs, except MmLeuRS (Mycoplasma mobile LeuRS). The substitute of CP1 in MmLeuRS is a nonapeptide (MmLinker). In the present study, we show that the MmLinker, which is critical for the aminoacylation activity of MmLeuRS, could confer remarkable tRNA-charging activity on the inactive CP1-deleted LeuRS from Escherichia coli (EcLeuRS) and Aquifex aeolicus (AaLeuRS). Furthermore, CP1 from EcLeuRS could functionally compensate for the MmLinker and endow MmLeuRS with post-transfer editing capability. These investigations provide a mechanistic framework for the modular construction of aaRSs and their co-ordination to achieve catalytic efficiency and fidelity. These results also show that the pre-transfer editing function of LeuRS originates from its conserved synthetic domain and shed light on future study of the mechanism. PMID:22292813

  2. 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

  3. Early life determinants of physical activity in 11 to 12 year olds: cohort study

    PubMed Central

    2008-01-01

    Objective To examine factors in early life (up to age 5 years) that are associated with objectively measured physical activity in 11-12 year olds. Design Prospective cohort study. Setting Avon longitudinal study of parents and children, United Kingdom. Participants Children aged 11-12 years from the Avon longitudinal study of parents and children. Main outcome measure Physical activity levels in counts per minute (cpm) and minutes of moderate to vigorous physical activity for seven days measured with a uniaxial actigraph accelerometer. Results Valid actigraph data, defined as at least three days of physical activity for at least 10 hours a day, were collected from 5451 children. Several factors were associated with physical activity at ages 11-12 years. Regression coefficients are compared with the baseline of “none” for categorical variables: maternal brisk walking during pregnancy (regression coefficient 5.0, 95% confidence interval −8.5 to 18.5; cpm for <1 h/wk and ≥2 h/wk of physical activity 17.7, 5.3 to 30.1), maternal swimming during pregnancy (21.5, 10.9 to 32.1 and cpm for <1 h/wk and ≥2 h/wk of physical activity 24.2, 7.8 to 40.7), parents’ physical activity when the child was aged 21 months (28.5, 15.2 to 41.8 and cpm of physical activity for either parent active and both parents active 33.5, 17.8 to 49.3), and parity assessed during pregnancy (2.9, −7.6 to 13.4 and cpm of physical activity for 1 and ≥2 parity 21.2, 7.1 to 35.3). Conclusions Few factors in early life predicted later physical activity in 11-12 year olds. Parents’ physical activity during pregnancy and early in the child’s life showed a modest association with physical activity of the child at age 11-12 years, suggesting that active parents tend to raise active children. Helping parents to increase their physical activity therefore may promote children’s activity. PMID:18037616

  4. Occipital MEG Activity in the Early Time Range (<300 ms) Predicts Graded Changes in Perceptual Consciousness.

    PubMed

    Andersen, Lau M; Pedersen, Michael N; Sandberg, Kristian; Overgaard, Morten

    2016-06-01

    Two electrophysiological components have been extensively investigated as candidate neural correlates of perceptual consciousness: An early, occipitally realized component occurring 130-320 ms after stimulus onset and a late, frontally realized component occurring 320-510 ms after stimulus onset. Recent studies have suggested that the late component may not be uniquely related to perceptual consciousness, but also to sensory expectations, task associations, and selective attention. We conducted a magnetoencephalographic study; using multivariate analysis, we compared classification accuracies when decoding perceptual consciousness from the 2 components using sources from occipital and frontal lobes. We found that occipital sources during the early time range were significantly more accurate in decoding perceptual consciousness than frontal sources during both the early and late time ranges. These results are the first of its kind where the predictive values of the 2 components are quantitatively compared, and they provide further evidence for the primary importance of occipital sources in realizing perceptual consciousness. The results have important consequences for current theories of perceptual consciousness, especially theories emphasizing the role of frontal sources. PMID:26009612

  5. The antioxidative potential of farrerol occurs via the activation of Nrf2 mediated HO-1 signaling in RAW 264.7 cells.

    PubMed

    Ci, Xinxin; Lv, Hongming; Wang, Lidong; Wang, Xiaosong; Peng, Liping; Qin, F Xiao-Feng; Cheng, Genhong

    2015-09-01

    Farrerol, (S)-2,3-dihydro-5,7-dihydroxy-2-(4-hydroxyphenyl)-6,8-dimethyl-4-benzopyrone, isolated from rhododendron, has been shown to have antioxidative potential, but the molecular mechanism underlying this activity remains unclear. The inducible expression of heme oxygenase-1 (HO-1), a potent antioxidative and cytoprotective enzyme, is known to play an important role in cytoprotection in a variety of pathological models. In this study, we evaluated the antioxidative potential of farrerol against oxidative damage and investigated its antioxidative mechanism in RAW 264.7 cells. The molecular mechanism underlying the cytoprotective function of farrerol was determined by analyzing intracellular signaling pathways, transcriptional activation and the inhibitory effect of HO-1 on ROS production. Farrerol induced antioxidant enzymes mRNA expression, HO-1 protein expression and nuclear translocation of NF-E2-related factor 2 in RAW 264.7 macrophage cells. Farrerol down-regulated the expression of the Keap1 protein and the thiol reducing agents attenuated farrerol-induced HO-1 expression. Further investigation utilizing Western blotting and specific inhibitors of Akt, p38, JNK and ERK demonstrated that Akt, p38, and ERK axis of signaling pathway mediates HO-1 expression. Moreover, tert-butyl hydroperoxide (t-BHP)-induced oxidative damage was ameliorated by farrerol treatment in a dose-dependent manner, which was abolished by Akt, p38, ERK and HO-1 inhibitors (Snpp). It is hence likely that farrerol inactivated KEAP-1 or activated the Akt, p38 and ERK to facilitate the release of Nrf2 from Keap1 and subsequent reduced the intracellular production of reactive oxygen species via the induction of HO-1 expression. These results support the central role of HO-1 in the cytoprotective effect of farrerol. PMID:26111761

  6. A novel naturally occurring salicylic acid analogue acts as an anti-inflammatory agent by inhibiting nuclear factor-kappaB activity in RAW264.7 macrophages.

    PubMed

    Zhang, Tiantai; Sun, Lan; Liu, Rui; Zhang, Dan; Lan, Xi; Huang, Chao; Xin, Wenyu; Wang, Chao; Zhang, Dongming; Du, Guanhua

    2012-03-01

    Methyl salicylate 2-O-β-D-lactoside (DL0309), is a molecule chemically related to salicylic acid that is isolated from Gaultheria yunnanensis (FRANCH.) REHDER (G. yunnanensis). G. yunnanensis, a traditional Chinese herbal medicine, is widely used for treating rheumatoid arthritis, swelling, pain, trauma, and chronic tracheitis. In the present study, we explored the mechanism whereby DL0309 exerts anti-inflammatory effects, using the model of lipopolysaccharide (LPS)-treated RAW264.7 cells. We examined the effects of DL0309 on LPS-induced nuclear factor-kappaB (NF-κB) activity by Western blot analysis, cell imaging analysis and an electrophoretic mobility shift assay (EMSA). Production of pro-inflammatory cytokines was also measured. Our observations indicate that DL0309 suppressed production of nitric oxide (NO), reactive oxygen species (ROS) and the pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), in a concentration-dependent manner. The phosphorylation of IKK-β and degradation of IκB-α by LPS were both inhibited by DL0309 in the cytoplasm. The increased protein level of NF-κB by LPS in the nucleus was also reduced by DL0309. Consistent with these results, we found that DL0309 prevents the nuclear translocation and DNA binding activity of NF-κB. Finally, our results demonstrate that DL0309 exerts anti-inflammatory effects, by inhibiting the production of pro-inflammatory cytokines and suppressing of the activation of the NF-κB signaling pathway in LPS-treated macrophage cells. Therefore, DL0309 may have therapeutic potential for treating inflammatory diseases by regulating the NF-κB pathway and pro-inflammatory cytokine production. PMID:22292506

  7. PHYSICAL EFFECTS OCCURRING DURING GENERATION AND AMPLIFICATION OF LASER RADIATION: Discharge energy balance in the nitrogen-containing active medium of an electron-beam-controlled CO laser

    NASA Astrophysics Data System (ADS)

    Dolinina, V. I.; Koterov, V. N.; Pyatakhin, Mikhail V.; Urin, B. M.

    1989-02-01

    Numerical methods were used to investigate theoretically the dynamics of the energy balance of a discharge in a CO-N2 mixture, taking into account the mutual influence of the distributions of the electron energy and of the populations of the molecules over the vibrational levels. It was shown that this influence plays a decisive part in substantially redistributing the pump energy between the vibrational levels of the CO and N2 molecules in favor of the N2 molecules. A stabilizing action of the nitrogen on the thermal regime of the CO laser-active medium was discovered and the range of optimal CO:N2 ratios was determined.

  8. Loss of DNA-protein crosslinks from formaldehyde-exposed cells occurs through spontaneous hydrolysis and an active repair process linked to proteosome function.

    PubMed

    Quievryn, G; Zhitkovich, A

    2000-08-01

    DNA-protein crosslinks (DPC) involving all major histones are the dominant form of DNA damage in formaldehyde-exposed cells. In order to understand the repair mechanisms for these lesions we conducted detailed analysis of the stability of formaldehyde-induced DPC in vitro and in human cells. DNA-histone linkages were found to be hydrolytically unstable, with t(1/2) = 18.3 h at 37 degrees C. When histones were allowed to remain bound to DNA after crosslink breakage, the half-life of DPC increased to 26.3 h. This suggests that approximately 30% of spontaneously broken DPC could be re-established under physiological conditions. The half-lives of DPC in three human cell lines (HF/SV fibroblasts, kidney Ad293 and lung A549 cells) were similar and averaged 12.5 h (range 11.6-13.0 h). After adjustment for spontaneous loss, an active repair process was calculated to eliminate DPC from these cells with an average t(1/2) = 23.3 h. Removal of DPC from peripheral human lymphocytes was slower (t(1/2) = 18.1 h), due to inefficient active repair (t(1/2) = 66.6 h). This indicates that the major portion of DPC is lost from lymphocytes through spontaneous hydrolysis rather than being actively repaired. Depletion of intracellular glutathione from A549 cells had no significant effect on the initial levels of DPC, the rate of their repair or cell survival. Nucleotide excision repair does not appear to be involved in the removal of DPC, since the kinetics of DPC elimination in XP-A and XP-F fibroblasts were very similar to normal cells. Incubation of normal or XP-A cells with lactacystin, a specific inhibitor of proteosomes, caused inhibition of DPC repair, suggesting that the active removal of DPC in cells may involve proteolytic degradation of crosslinked proteins. XP-F cells showed somewhat higher sensitivity to formaldehyde, possibly signaling participation of XPF protein in the removal of residual peptide-DNA adducts. PMID:10910961

  9. 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

  10. Early glial activation, synaptic changes and axonal pathology in the thalamocortical system of Niemann–Pick type C1 mice

    PubMed Central

    Pressey, Sarah N.R.; Smith, David A.; Wong, Andrew M.S.; Platt, Frances M.; Cooper, Jonathan D.

    2012-01-01

    Niemann–Pick disease type C (NPC) is an inherited lysosomal storage disease characterised by accumulation of cholesterol and glycosphingolipids. NPC patients suffer a progressive neurodegenerative phenotype presenting with motor dysfunction, mental retardation and cognitive decline. To examine the onset and progression of neuropathological insults in NPC we have systematically examined the CNS of a mouse model of NPC1 (Npc1−/− mice) at different stages of the disease course. This revealed a specific spatial and temporal pattern of neuropathology in Npc1−/− mice, highlighting that sensory thalamic pathways are particularly vulnerable to loss of NPC1 resulting in neurodegeneration in Npc1−/− mice. Examination of markers of astrocytosis and microglial activation revealed a particularly pronounced reactive gliosis in the thalamus early in the disease, which subsequently also occurred in interconnected cortical laminae at later ages. Our examination of the precise staging of events demonstrate that the relationship between glia and neurons varies between brain regions in Npc1−/− mice, suggesting that the cues causing glial reactivity may differ between brain regions. In addition, aggregations of pre-synaptic markers are apparent in white matter tracts and the thalamus and are likely to be formed within axonal spheroids. Our data provide a new perspective, revealing a number of events that occur prior to and alongside neuron loss and highlighting that these occur in a pathway dependent manner. PMID:22198570

  11. 3xTg-AD Mice Exhibit an Activated Central Stress Axis during Early-Stage Pathology

    PubMed Central

    Hebda-Bauer, Elaine K.; Simmons, Tracy A.; Sugg, Andrew; Ural, Eren; Stewart, James A.; Beals, James L.; Wei, Qiang; Watson, Stanley J.; Akil, Huda

    2012-01-01

    Activation of the hypothalamic-pituitary-adrenal (HPA) axis occurs in response to the organism’s innate need for homeostasis. The glucocorticoids (GCs) that are released into the circulation upon acute activation of the HPA axis perform stress-adaptive functions and provide negative feedback to turn off the HPA axis, but can be detrimental when in excess. Long-term activation of the HPA axis (such as with chronic stress) enhances susceptibility to neuronal dysfunction and death, and increases vulnerability to Alzheimer’s disease (AD). However, little is known how components of the HPA axis, upstream of GCs, impact vulnerability to AD. This study examined basal gene expression of stress-related molecules in brains of 3xTg-AD mice during early-stage pathology. Basal glucocorticoid levels and mRNA expression of the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and corticotropic releasing hormone (CRH) in several stress- and emotionality-related brain regions were measured in 3–4-month-old 3xTg-AD mice. Despite normal glucocorticoid levels, young 3xTg-AD mice exhibit an activated central HPA axis, with altered mRNA levels of MR and GR in the hippocampus, GR and CRH in the paraventricular nucleus of the hypothalamus, GR and CRH in the central nucleus of the amygdala, and CRH in the bed nucleus of the stria terminalis. This HPA axis activation is present during early-stage neuropathology when 3xTg-AD mice show mild behavioral changes, suggesting an ongoing neuroendocrine regulation that precedes the onset of severe AD-like pathology and behavioral deficits. PMID:22976078

  12. 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.

  13. Spatial and temporal variations in fault activity during early development of rift polarity within the offshore Corinth rift, central Greece

    NASA Astrophysics Data System (ADS)

    Nixon, C. W.; Moyle, A.; McNeill, L. C.; Bell, R. E.; Bull, J. M.; Henstock, T.

    2014-12-01

    The Corinth rift, Greece, is a young, highly active rift. A combined dense network of marine geophysical data and onshore exposure makes Corinth a natural laboratory for investigating early rift and fault formation. Rifts commonly develop a primary polarity during their formation resulting from a dominant fault set. However, how this occurs and develops is less clear. Here we characterise this process by establishing how a dominant fault set develops within the Corinth rift. Using a high spatio-temporal resolution chronostratigraphic and rift fault model, we investigate the variations in the distribution of displacement and faulting along and across the rift axis; focussing on the partitioning of deformation between N- and S-dipping faults, at a temporal resolution of ca. 100 kyr or less. Along-strike cumulative fault displacement profiles indicate overall equal distribution of strain between major S- and N-dipping faults over the last ca. 1.5 Myr. In detail, two peaks in cumulative displacement coincide with the early development of two discrete depocentres before ca. 600 ka. Since this time, displacement has become focussed on N-dipping faults with S-dipping faults becoming less active. Syn-rift isochore maps illuminate this change: a switch in rift polarity from a dominant N-thickening depocentre to a dominant S-thickening depocentre between ca. 530-420 kyr (a rapid change in rift structure and strain distribution). This change is accommodated by transfer of activity between major faults but also by formation of numerous non-basement cutting small faults. As major S-dipping faults decrease in slip rate from ca. 600 ka, they become segmented into smaller faults with variable slip rates. In contrast, N-dipping faults on the rift's southern margin, with increased activity post ~0.5-0.4 Ma, become kinematically and geometrically linked with almost equal slip rates along strike by ca. 130 kyr, controlling the single major depocentre of the present day. Our results

  14. 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

  15. 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

  16. Measuring Physical Activity in Older Adults with and without Early Stage Alzheimer’s Disease

    PubMed Central

    Watts, Amber S.; Vidoni, Eric D.; Loskutova, Natalia; Johnson, David K.; Burns, Jeffrey M.

    2013-01-01

    We compared subjective reports of physical activity with objective measures of physical fitness including cardiorespiratory capacity, body composition, and physical performance in 146 older adults with and without early stage Alzheimer’s disease (ESAD). Respondents reported primarily unstructured and low-intensity activities, including walking and housework. Individuals with ESAD participated in fewer and lower intensity physical activities than those without ESAD. In those without ESAD, housework was related to lower body mass index, leisure walking was related to faster speed on a timed walking test, and participation in sports was related to higher peak oxygen intake. In individuals with ESAD, reported physical activities did not predict any of the physical fitness, body composition, or physical performance measures. We conclude that measures of physical activity require expansion of unstructured and low intensity activities to improve sensitivity in sedentary populations, especially in older adults with ESAD. PMID:24062599

  17. Observed multivariable signals of late 20th and early 21st century volcanic activity

    NASA Astrophysics Data System (ADS)

    Santer, Benjamin D.; Solomon, Susan; Bonfils, Céline; Zelinka, Mark D.; Painter, Jeffrey F.; Beltran, Francisco; Fyfe, John C.; Johannesson, Gardar; Mears, Carl; Ridley, David A.; Vernier, Jean-Paul; Wentz, Frank J.

    2015-01-01

    The relatively muted warming of the surface and lower troposphere since 1998 has attracted considerable attention. One contributory factor to this "warming hiatus" is an increase in volcanically induced cooling over the early 21st century. Here we identify the signals of late 20th and early 21st century volcanic activity in multiple observed climate variables. Volcanic signals are statistically discernible in spatial averages of tropical and near-global SST, tropospheric temperature, net clear-sky short-wave radiation, and atmospheric water vapor. Signals of late 20th and early 21st century volcanic eruptions are also detectable in near-global averages of rainfall. In tropical average rainfall, however, only a Pinatubo-caused drying signal is identifiable. Successful volcanic signal detection is critically dependent on removal of variability induced by the El Niño-Southern Oscillation.

  18. The cleavage of nuclear DNA into high molecular weight DNA fragments occurs not only during apoptosis but also accompanies changes in functional activity of the nonapoptotic cells.

    PubMed

    Solov'yan, V T; Andreev, I O; Kolotova, T Y; Pogribniy, P V; Tarnavsky, D T; Kunakh, V A

    1997-08-25

    In this paper we demonstrate that apoptosis in primary culture of murine thymocytes and in continuously growing human cells is associated with the progressive disintegration of nuclear DNA into high molecular weight (HMW)-DNA fragments of about 50-150 kb. We also show that the formation of similarly sized HMW-DNA fragments takes place in the same cells in the absence of apoptotic inducers. Unlike an apoptotic fragmentation of nuclear DNA, the formation of HMW-DNA fragments in nonapoptotic cells is rapidly induced, has no correlation with the cell death, and is not associated with the development of oligonucleosomal "ladder" or apoptotic changes in nuclear morphology. The disintegration of DNA into HMW-fragments is also observed in nuclei isolated from healthy, nonapoptosizing tissues of various eukaryotes. We show that the formation of HMW-DNA fragments in the absence of apoptotic inducers is strongly dependent on the ionic detergents, is responsive to the topoisomerase II-specific poison, teniposide, and is completely reversible under conditions that favor topoisomerase II-dependent rejoining reaction. Also, we demonstrate that the formation of HMW-DNA fragments in continuously growing cell lines caused either by serum deprivation or monolayer establishment is of a transient nature and rapidly reverses to the control level following serum addition or dilution of monolayer. The results suggest that the cleavage of nuclear DNA into HMW-DNA fragments is associated not only with apoptosis but also accompanies changes in functional activity of nonapoptotic cells. PMID:9281361

  19. Agrobacterium T-DNA integration into the plant genome can occur without the activity of key non-homologous end-joining proteins.

    PubMed

    Park, So-Yon; Vaghchhipawala, Zarir; Vasudevan, Balaji; Lee, Lan-Ying; Shen, Yunjia; Singer, Kamy; Waterworth, Wanda M; Zhang, Zhanyuan J; West, Christopher E; Mysore, Kirankumar S; Gelvin, Stanton B

    2015-03-01

    Non-homologous end joining (NHEJ) is the major model proposed for Agrobacterium T-DNA integration into the plant genome. In animal cells, several proteins, including KU70, KU80, ARTEMIS, DNA-PKcs, DNA ligase IV (LIG4), Ataxia telangiectasia mutated (ATM), and ATM- and Rad3-related (ATR), play an important role in 'classical' (c)NHEJ. Other proteins, including histone H1 (HON1), XRCC1, and PARP1, participate in a 'backup' (b)NHEJ process. We examined transient and stable transformation frequencies of Arabidopsis thaliana roots mutant for numerous NHEJ and other related genes. Mutants of KU70, KU80, and the plant-specific DNA Ligase VI (LIG6) showed increased stable transformation susceptibility. However, these mutants showed transient transformation susceptibility similar to that of wild-type plants, suggesting enhanced T-DNA integration in these mutants. These results were confirmed using a promoter-trap transformation vector that requires T-DNA integration into the plant genome to activate a promoterless gusA (uidA) gene, by virus-induced gene silencing (VIGS) of Nicotiana benthamiana NHEJ genes, and by biochemical assays for T-DNA integration. No alteration in transient or stable transformation frequencies was detected with atm, atr, lig4, xrcc1, or parp1 mutants. However, mutation of parp1 caused high levels of T-DNA integration and transgene methylation. A double mutant (ku80/parp1), knocking out components of both NHEJ pathways, did not show any decrease in stable transformation or T-DNA integration. Thus, T-DNA integration does not require known NHEJ proteins, suggesting an alternative route for integration. PMID:25641249

  20. 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. PMID:25769181

  1. Activation of PI3K/mTOR pathway occurs in most adult low-grade gliomas and predicts patient survival.

    PubMed

    McBride, Sean M; Perez, Daniel A; Polley, Mei-Yin; Vandenberg, Scott R; Smith, Justin S; Zheng, Shichun; Lamborn, Kathleen R; Wiencke, John K; Chang, Susan M; Prados, Michael D; Berger, Mitchel S; Stokoe, David; Haas-Kogan, Daphne A

    2010-03-01

    Recent evidence suggests the Akt-mTOR pathway may play a role in development of low-grade gliomas (LGG). We sought to evaluate whether activation of this pathway correlates with survival in LGG by examining expression patterns of proteins within this pathway. Forty-five LGG tumor specimens from newly diagnosed patients were analyzed for methylation of the putative 5'-promoter region of PTEN using methylation-specific PCR as well as phosphorylation of S6 and PRAS40 and expression of PTEN protein using immunohistochemistry. Relationships between molecular markers and overall survival (OS) were assessed using Kaplan-Meier methods and exact log-rank test. Correlation between molecular markers was determined using the Mann-Whitney U and Spearman Rank Correlation tests. Eight of the 26 patients with methylated PTEN died, as compared to 1 of 19 without methylation. There was a trend towards statistical significance, with PTEN methylated patients having decreased survival (P = 0.128). Eight of 29 patients that expressed phospho-S6 died, whereas all 9 patients lacking p-S6 expression were alive at last follow-up. There was an inverse relationship between expression of phospho-S6 and survival (P = 0.029). There was a trend towards decreased survival in patients expressing phospho-PRAS40 (P = 0.077). Analyses of relationships between molecular markers demonstrated a statistically significant positive correlation between expression of p-S6(235) and p-PRAS40 (P = 0.04); expression of p-S6(240) correlated positively with PTEN methylation (P = 0.04) and negatively with PTEN expression (P = 0.03). Survival of LGG patients correlates with phosphorylation of S6 protein. This relationship supports the use of selective mTOR inhibitors in the treatment of low grade glioma. PMID:19705067

  2. 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

  3. 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

  4. Role of Magnesium Chelatase Activity in the Early Steps of the Tetrapyrrole Biosynthetic Pathway1

    PubMed Central

    Papenbrock, Jutta; Mock, Hans-Peter; Tanaka, Ryouichi; Kruse, Elisabeth; Grimm, Bernhard

    2000-01-01

    Magnesium-protoporphyrin IX chelatase (Mg-chelatase) is located at the branchpoint of tetrapyrrole biosynthesis, at which point protoporphyrin IX is distributed for the synthesis of chlorophyll and heme. We investigated the regulatory contribution of Mg-chelatase to the flow of metabolites. In plants, the enzyme complex consists of three subunits, designated CHL D, CHL I, and CHL H. Transgenic tobacco (Nicotiana tabacum) plants expressing antisense RNA for the Mg-chelatase subunit CHL H were analyzed to elucidate further the role of Mg-chelatase in the distribution of protoporphyrin IX into the branched tetrapyrrolic pathway. The transgenic plants displayed a reduced growth rate and chlorophyll deficiency. Both phenotypical properties were correlated with lower Mg-chelatase activity. Unexpectedly, less protoporphyrin IX and heme accumulated, and a decrease in 5-aminolevulinate (ALA)-synthesizing capacity and ALA dehydratase activity paralleled the progressive reduction in Mg-chelatase activity in the transformants compared with control plants. The reduced activities of the early enzymatic steps corresponded with lower levels of transcripts encoding glutamyl-tRNA reductase and ALA-dehydratase. The decreased expression and activities of early enzymes in the pathway could be explained by a feedback-controlled mechanism in response to lower Mg-chelatase activity. We discuss intercompartmental signaling that synchronizes the activities of the first steps in tetrapyrrolic metabolism with the late steps for the synthesis of end products. PMID:10759511

  5. Response of early active rheumatoid arthritis to tumor necrosis factor inhibitors: evaluation by magnetic resonance imaging.

    PubMed

    Hirose, Wataru; Nishikawa, Kenichiro; Hirose, Masuko; Nanki, Toshihiro; Sugimoto, Hideharu

    2009-01-01

    Inflammatory changes (synovitis and bone marrow edema) and destructive changes (bone erosion) were evaluated by magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA), and their relations with disease activity were assessed during treatment with tumor necrosis factor (TNF) inhibitors. Ten patients with early active RA underwent MRI at 0 and 16 weeks of TNF-inhibitor treatment. The carpal bones of the dominant hand were evaluated by the outcome measures in rheumatology clinical trials MRI score for RA. After 16 weeks, the mean disease activity score (DAS 28) decreased significantly from 5.54 to 2.70, while the number of tender joints, number of swollen joints, and inflammatory parameters were also significantly improved. The mean synovitis and marrow edema scores determined by MRI showed a significant decrease from 6.1 to 2.2 and 12.8 to 6.2, respectively, while the annual bone-erosion progression score decreased from 12.6 to 2.0. Although synovitis persisted in some patients, imaging remission was achieved in two patients. In conclusion, TNF-inhibitor therapy achieved an early decrease of disease activity and MRI revealed amelioration of joint destruction. The MRI score for RA is useful for assessing the early response to TNF inhibitors. PMID:18762862

  6. 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.

  7. 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

  8. 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

  9. 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

  10. Aurora A drives early signalling and vesicle dynamics during T-cell activation.

    PubMed

    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

  11. Contraceptive steroid concentrations in women with early active schistosomiasis: lack of effect of antischistosomal drugs.

    PubMed

    el-Raghy, I; Back, D J; Osman, F; Orme, M L; Fathalla, M

    1986-04-01

    Plasma concentrations of the oral contraceptive steroids (OCS) ethinyloestradiol (EE2) and levonorgestrel (LNG) have been determined in women with early active schistosomiasis and compared to those obtained in healthy volunteers. Steroid concentrations following a single dose of Ovral (500 micrograms LNG, 50 micrograms EE2) or during a multiple dose regimen were unaffected by the disease. There was no significant effect of the antischistosomal drugs praziquantel (40 mg X kg-1) or metrifonate (10 mg X kg-1 X 3 at 2-week intervals) on plasma steroid concentrations. In regular users of OCS, significantly higher concentrations of LNG were observed than in women who received only a single dose. We conclude that there is no pharmacokinetic reason for withholding OCS from patients with early active schistosomiasis who are also receiving either praziquantel or metrifonate. PMID:3089682

  12. 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.

  13. 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

  14. Dynamic changes in network activations characterize early learning of a natural language.

    PubMed

    Plante, Elena; Patterson, Dianne; Dailey, Natalie S; Kyle, R Almyrde; Fridriksson, Julius

    2014-09-01

    Those who are initially exposed to an unfamiliar language have difficulty separating running speech into individual words, but over time will recognize both words and the grammatical structure of the language. Behavioral studies have used artificial languages to demonstrate that humans are sensitive to distributional information in language input, and can use this information to discover the structure of that language. This is done without direct instruction and learning occurs over the course of minutes rather than days or months. Moreover, learners may attend to different aspects of the language input as their own learning progresses. Here, we examine processing associated with the early stages of exposure to a natural language, using fMRI. Listeners were exposed to an unfamiliar language (Icelandic) while undergoing four consecutive fMRI scans. The Icelandic stimuli were constrained in ways known to produce rapid learning of aspects of language structure. After approximately 4 min of exposure to the Icelandic stimuli, participants began to differentiate between correct and incorrect sentences at above chance levels, with significant improvement between the first and last scan. An independent component analysis of the imaging data revealed four task-related components, two of which were associated with behavioral performance early in the experiment, and two with performance later in the experiment. This outcome suggests dynamic changes occur in the recruitment of neural resources even within the initial period of exposure to an unfamiliar natural language. PMID:25058056

  15. Dynamic Changes in Network Activations Characterize Early Learning of a Natural Language

    PubMed Central

    Plante, Elena; Patterson, Dianne; Dailey, Natalie S.; Almyrde, Kyle, R.; Fridriksson, Julius

    2014-01-01

    Those who are initially exposed to an unfamiliar language have difficulty separating running speech into individual words, but over time will recognize both words and the grammatical structure of the language. Behavioral studies have used artificial languages to demonstrate that humans are sensitive to distributional information in language input, and can use this information to discover the structure of that language. This is done without direct instruction and learning occurs over the course of minutes rather than days or months. Moreover, learners may attend to different aspects of the language input as their own learning progresses. Here, we examine processing associated with the early stages of exposure to a natural language, using fMRI. Listeners were exposed to an unfamiliar language (Icelandic) while undergoing four consecutive fMRI scans. The Icelandic stimuli were constrained in ways known to produce rapid learning of aspects of language structure. After approximately 4 minutes of exposure to the Icelandic stimuli, participants began to differentiate between correct and incorrect sentences at above chance levels, with significant improvement between the first and last scan. An independent component analysis of the imaging data revealed four task-related components, two of which were associated with behavioral performance early in the experiment, and two with performance later in the experiment. This outcome suggests dynamic changes occur in the recruitment of neural resources even within the initial period of exposure to an unfamiliar natural language. PMID:25058056

  16. Early pharmacological inhibition of angiotensin-I converting enzyme activity induces obesity in adulthood

    PubMed Central

    de Picoli Souza, Kely; da Silva, Elton D.; Batista, Elice C.; Reis, Felipe C. G.; Silva, Sylvia M. A.; Castro, Charlles H. M.; Luz, Jaqueline; Pesquero, Jorge L.; dos Santos, Edson L.; Pesquero, João B.

    2015-01-01

    We have investigated early programming of body mass in order to understand the multifactorial etiology of obesity. Considering that the renin-angiotensin system (RAS) is expressed and functional in the white adipose tissue (WAT) and modulates its development, we reasoned whether early transitory inhibition of angiotensin-I converting enzyme activity after birth could modify late body mass development. Therefore, newborn Wistar rats were treated with enalapril (10 mg/kg of body mass) or saline, starting at the first day of life until the age of 16 days. Between days ninetieth and hundred and eightieth, a group of these animals received high fat diet (HFD). Molecular, biochemical, histological, and physiological data were collected. Enalapril treated animals presented hyperphagia, overweight, and increased serum level of triglycerides, total cholesterol and leptin, in adult life. Body composition analyses revealed higher fat mass with increased adipocyte size in these animals. Molecular analyses revealed that enalapril treatment increases neuropeptide Y (NPY) and cocaine- and amphetamine-regulated transcript (CART) gene expression in hypothalamus, fatty acid synthase (FAS), and hormone-sensitive lipase (HSL) gene expression in retroperitoneal WAT, and decreases peroxixome proliferators-activated receptor (PPAR)γ, PPARα, uncoupling protein (UCP)2, and UCP3 gene expression in WAT. The results of the current study indicate that enalapril administration during early postnatal development increases body mass, adiposity and serum lipids in adulthood associated with enhanced food intake and decreased metabolic activity in WAT, predisposing to obesity in adulthood. PMID:25926796

  17. 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.

  18. Active cardiac model and its application on structure detection from early fetal ultrasound sequences.

    PubMed

    Deng, Yinhui; Wang, Yuanyuan; Shen, Yuzhong; Chen, Ping

    2012-04-01

    The structure of an early fetal heart provides vital information for the diagnosis of fetus defects. However, early fetal hearts are difficult to detect due to their relatively small size and the low signal-to-noise ratio of ultrasound images. In this paper, a novel method is proposed for automatic detection of early fetal cardiac structure from ultrasound images. The proposed method consists of two major parts which are the preprocessing phase and the active cardiac model: (1) The preprocessing phase consists of two sub-steps. (a) The region of interest is first automatically selected based on an accumulated motion image, which is able to represent the motion information of the fetal heart more accurately. (b) Then by combining Rayleigh-trimmed filter and anisotropic diffusion in 3-dimensional space, a despeckling method is developed to suppress the speckle noise and emphasize the motion information for subsequent cardiac structure detection. (2) The active cardiac model is proposed for the detection of fetal heart structure, which is a key contribution of this paper. It takes into account both the structure and motion information of fetal hearts simultaneously. Both learning and inference of the active cardiac model are described in the paper. Experiments on seven ultrasound sequences demonstrate the effectiveness of the proposed method. PMID:21620676

  19. Matrix metalloproteinase activation by free neutrophil elastase contributes to bronchiectasis progression in early cystic fibrosis.

    PubMed

    Garratt, Luke W; Sutanto, Erika N; Ling, Kak-Ming; Looi, Kevin; Iosifidis, Thomas; Martinovich, Kelly M; Shaw, Nicole C; Kicic-Starcevich, Elizabeth; Knight, Darryl A; Ranganathan, Sarath; Stick, Stephen M; Kicic, Anthony

    2015-08-01

    Neutrophil elastase is the most significant predictor of bronchiectasis in early-life cystic fibrosis; however, the causal link between neutrophil elastase and airway damage is not well understood. Matrix metalloproteinases (MMPs) play a crucial role in extracellular matrix modelling and are activated by neutrophil elastase. The aim of this study was to assess if MMP activation positively correlates with neutrophil elastase activity, disease severity and bronchiectasis in young children with cystic fibrosis.Total MMP-1, MMP-2, MMP-7, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-2 and TIMP-1 levels were measured in bronchoalveolar lavage fluid collected from young children with cystic fibrosis during annual clinical assessment. Active/pro-enzyme ratio of MMP-9 was determined by gelatin zymography. Annual chest computed tomography imaging was scored for bronchiectasis.A higher MMP-9/TIMP-1 ratio was associated with free neutrophil elastase activity. In contrast, MMP-2/TIMP-2 ratio decreased and MMP-1 and MMP-7 were not detected in the majority of samples. Ratio of active/pro-enzyme MMP-9 was also higher in the presence of free neutrophil elastase activity, but not infection. Across the study cohort, both MMP-9/TIMP-1 and active MMP-9 were associated with progression of bronchiectasis.Both MMP-9/TIMP-1 and active MMP-9 increased with free neutrophil elastase and were associated with bronchiectasis, further demonstrating that free neutrophil elastase activity should be considered an important precursor to cystic fibrosis structural disease. PMID:25929954

  20. Endometrial phospholipase A2 activity during the oestrous cycle and early pregnancy in mares.

    PubMed

    Ababneh, M M; Troedsson, M H T

    2013-02-01

    The aim of this study was to determine phospholipase A2 (PLA2) kinetics and activity in the mare's endometrium during the oestrous cycle and early pregnancy. Phospholipase A2 is responsible for the liberation of arachidonic acid from phospholipids, which is the first limiting step in prostaglandins synthesis. Phospholipase A2 activity was measured using an assay based on the liberation of oleic acid from 1-palmitoyl-2-[(14) C] oleoyl phosphatidylcholine. The enzyme was shown to be calcium dependent, to have an optimum pH of 8 and an apparent Michaelis constant of 127 μM. Enzyme activity was low in the endometrium of early luteal phase tissue but increased significantly (p < 0.001) during the late luteal phase (5.39 ± 0.16; 3.48 ± 0.33, 6.85 ± 0.59, and 9.96 ± 1.23 nmol oleic acid released/mg protein at oestrus, and Days 3, 8 and 14 after ovulation, respectively). The mean PLA2 activity in endometrial tissue from pregnant mares (4.23 ± 0.74) was significantly lower (p < 0.01) than from cyclic animals during late dioestrus (9.96 ± 1.23). The results indicate that PLA2 activity in equine endometrium changes with the stage of the oestrous cycle and thus may be influenced by systemic hormone concentrations. The inhibitory effects of conceptus products on secretion of prostaglandin during early pregnancy were associated with a competitive inhibitor that decreased endometrial PLA2 activity. PMID:22486770

  1. Assessing risk factors for early hip osteoarthritis in activity-related hip pain: a Delphi study

    PubMed Central

    Jackson, K A; Glyn-Jones, S; Batt, M E; Arden, N K; Newton, J L

    2015-01-01

    Objective Hip pain and injury as a result of activity can lead to the development of early hip osteoarthritis (OA) in susceptible individuals. Our understanding of the factors that increase susceptibility continues to evolve. The ability to clearly identify individuals (and cohorts) with activity-related hip pain who are at risk of early hip OA is currently lacking. The purpose of this study was to gain expert consensus on which key clinical measures might help predict the risk of early hip OA in individuals presenting with activity-related hip pain. The agreed measures would constitute a standardised approach to initial clinical assessment to help identify these individuals. Methods This Dephi study used online surveys to gain concordance of expert opinion in a structured process of ‘rounds’. In this study, we asked ‘What outcome measures are useful in predicting hip OA in activity-related hip pain?’ The Delphi panel consisted of experts from sport and exercise medicine, orthopaedics, rheumatology, physiotherapy and OA research. Results The study identified key clinical measures in the history, examination and investigations (plain anteroposterior radiograph and femoroacetabular impingement views) that the panel agreed would be useful in predicting future risk of hip OA when assessing activity-related hip pain. The panel also agreed that certain investigations and tests (eg, MR angiography) did not currently have a role in routine assessment. There was a lack of consensus regarding the role of MRI, patient-reported outcome measures (PROMs) and certain biomechanical and functional assessments. Conclusions We provide a standardised approach to the clinical assessment of patients with activity-related hip pain. Assessment measures rejected by the Delphi panel were newer, more expensive investigations that currently lack evidence. Assessment measures that did not reach consensus include MRI and PROMs. Their role remains ambiguous and would benefit from further

  2. Slow early growers have more muscle in relation to adult activity: Evidence from Cebu, Philippines

    PubMed Central

    Workman, Megan; McDade, Thomas W.; Adair, Linda S.; Kuzawa, Christopher W.

    2015-01-01

    Background/objectives Adult skeletal muscle mass (SMM) protects against type 2 diabetes but little is known about its developmental antecedents. We examined whether pace of early weight gain predicted adult SMM in a birth cohort from Cebu City, Philippines. Additionally, we examined whether increases in SMM associated with adult muscle-building exercise varied according to early growth. Subjects/methods Data came from 1472 participants of the Cebu Longitudinal Health and Nutrition Survey. Weight was measured at birth and at 6-month intervals through age 24 months. Adult SMM was estimated from anthropometric measurements when participants were 20-22 years old. Interviews provided information on adult exercise/lifestyle habits. Results SMM (mean ± SD) was 20.8 ± 3.9 kg (men) and 13.6 ± 3.4 kg (women). Faster early weight gain predicted higher adult SMM. After adjustment for height and lifestyle factors, strongest associations with SMM were found for 6-12 months growth in men (β=0.17, p=0.001) and for birth weight in women (β=0.14, p=0.001). Individuals who had grown slowly displayed greater SMM in association with adult weight lifting, basketball playing, and physically demanding forms of employment (men) or household chores (women). Conclusions These results suggest heightened sensitivity of activity-induced muscle hypertrophy among adults who were born light or who gained weight slowly as infants. Future research should test this finding by comparing responses of muscle mass to an intervention in slow v. fast early growers. Findings suggest that adults who display reduced SMM following suboptimal early growth may be good candidates for new anti-diabetes interventions that promote muscle-building activities. PMID:25782430

  3. A spinal opsin controls early neural activity and drives a behavioral light response

    PubMed Central

    Friedmann, Drew; Hoagland, Adam; Berlin, Shai; Isacoff, Ehud Y.

    2014-01-01

    Non-visual detection of light by the vertebrate hypothalamus, pineal, and retina is known to govern seasonal and circadian behaviors [1]. However, the expression of opsins in multiple other brain structures [2–4] suggests a more expansive repertoire for light-regulation of physiology, behavior, and development. Translucent zebrafish embryos express extra-retinal opsins early on [5, 6], at a time when spontaneous activity in the developing central nervous system plays a role in neuronal maturation and circuit formation [7]. Though the presence of extra-retinal opsins is well documented, the function of direct photoreception by the central nervous system remains largely unknown. Here we show that early activity in the zebrafish spinal central pattern generator (CPG) and the earliest locomotory behavior are dramatically inhibited by physiological levels of environmental light. We find that the photo-sensitivity of this circuit is conferred by vertebrate ancient long opsin (VALopA), which we show to be a Gαi-coupled receptor that is expressed in the neurons of the spinal network. Sustained photo-activation of VALopA not only suppresses spontaneous activity but also alters the maturation of time-locked correlated network patterns. These results uncover a novel role for non-visual opsins and a mechanism for environmental regulation of spontaneous motor behavior and neural activity in a circuit previously thought to be governed only by intrinsic developmental programs. PMID:25484291

  4. 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

  5. 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

  6. 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

  7. 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

  8. [The criteria of differentiated diagnostics of early arthritis on the basis of analysis of serum hyaluronidase and deoxyribonuclease activity].

    PubMed

    Volkova, M V; Kunder, E V

    2012-10-01

    The study analyzed serum hyaluronidase and deoxyribonuclease activity in patients with early arthritis--early rheumatoid arthritis and acute reactive arthritis. The criteria of their differential diagnostics were developed on the basis of data obtained. The genuine methods were applied to analyze hyaluronidase and deoxyribonuclease activity of blood serum based on formation of clot of etacridine acetate (rivanol) with hyaluronic acid and DNA inversely proportionally to their polymerization under the impact of enzymes. The increased serum hyaluronidase and deoxyribonuclease activity was established in patients with early arthritis as compared with control group (p < 0.001). The prevalence of mentioned types of activity under early rheumatoid arthritis as compared with acute reactive arthritis was detected too. The rests for differentiate diagnostics of early rheumatoid arthritis and acute reactive arthritis were developed conformed to criteria of the most useful diagnostic tests in rheumatology. PMID:23265051

  9. The impact of initiation: Early onset marijuana smokers demonstrate altered Stroop performance and brain activation.

    PubMed

    Sagar, K A; Dahlgren, M K; Gönenç, A; Racine, M T; Dreman, M W; Gruber, S A

    2015-12-01

    Marijuana (MJ) use is on the rise, particularly among teens and emerging adults. This poses serious public health concern, given the potential deleterious effects of MJ on the developing brain. We examined 50 chronic MJ smokers divided into early onset (regular MJ use prior to age 16; n=24) and late onset (age 16 or later; n=26), and 34 healthy control participants (HCs). All completed a modified Stroop Color Word Test during fMRI. Results demonstrated that MJ smokers exhibited significantly poorer performance on the Interference subtest of the Stroop, as well as altered patterns of activation in the cingulate cortex relative to HCs. Further, early onset MJ smokers exhibited significantly poorer performance relative to both HCs and late onset smokers. Additionally, earlier age of MJ onset as well as increased frequency and magnitude (grams/week) of MJ use were predictive of poorer Stroop performance. fMRI results revealed that while late onset smokers demonstrated a more similar pattern of activation to the control group, a different pattern was evident in the early onset group. These findings underscore the importance of assessing age of onset and patterns of MJ use and support the need for widespread education and intervention efforts among youth. PMID:25936584

  10. Early Reduction of Microglia Activation by Irradiation in a Model of Chronic Glaucoma

    PubMed Central

    Bosco, Alejandra; Crish, Samuel D.; Steele, Michael R.; Romero, Cesar O.; Inman, Denise M.; Horner, Philip J.; Calkins, David J.; Vetter, Monica L.

    2012-01-01

    Glaucoma is a neurodegenerative disease that results in the progressive decline and ultimate death of retinal ganglion cells (RGCs). While multiple risk factors are associated with glaucoma, the mechanisms leading to onset and progression of the disease remain unknown. Molecular analysis in various glaucoma models has revealed involvement of non-neuronal cell populations, including astrocytes, Mueller glia and microglia, at early stages of glaucoma. High-dose irradiation was reported to have a significant long-term protective effect in the DBA/2J (D2) mouse model of glaucoma, although the cellular and molecular basis for this effect remains unclear. In particular, the acute effects of irradiation on specific cell populations, including non-neuronal cells, in the D2 retina and nerve have not been assessed. Here we report that irradiation induces transient reduction in proliferating microglia within the optic nerve head and glial lamina within the first week post-irradiation. This was accompanied by reduced microglial activation, with no effect on astrocyte gliosis in those regions. At later stages we confirm that early high-dose irradiation of the mouse head results in improvement of axonal structural integrity and anterograde transport function, without reduction of intraocular pressure. Thus reduced microglial activation induced by irradiation at early stages is associated with reduced optic nerve and retinal neurodegeneration in the D2 mouse model of glaucoma. PMID:22952717

  11. Mapping of Brain Activity by Automated Volume Analysis of Immediate Early Genes.

    PubMed

    Renier, Nicolas; Adams, Eliza L; Kirst, Christoph; Wu, Zhuhao; Azevedo, Ricardo; Kohl, Johannes; Autry, Anita E; Kadiri, Lolahon; Umadevi Venkataraju, Kannan; Zhou, Yu; Wang, Victoria X; Tang, Cheuk Y; Olsen, Olav; Dulac, Catherine; Osten, Pavel; Tessier-Lavigne, Marc

    2016-06-16

    Understanding how neural information is processed in physiological and pathological states would benefit from precise detection, localization, and quantification of the activity of all neurons across the entire brain, which has not, to date, been achieved in the mammalian brain. We introduce a pipeline for high-speed acquisition of brain activity at cellular resolution through profiling immediate early gene expression using immunostaining and light-sheet fluorescence imaging, followed by automated mapping and analysis of activity by an open-source software program we term ClearMap. We validate the pipeline first by analysis of brain regions activated in response to haloperidol. Next, we report new cortical regions downstream of whisker-evoked sensory processing during active exploration. Last, we combine activity mapping with axon tracing to uncover new brain regions differentially activated during parenting behavior. This pipeline is widely applicable to different experimental paradigms, including animal species for which transgenic activity reporters are not readily available. PMID:27238021

  12. An initial phase of JNK activation inhibits cell death early in the endoplasmic reticulum stress response.

    PubMed

    Brown, Max; Strudwick, Natalie; Suwara, Monika; Sutcliffe, Louise K; Mihai, Adina D; Ali, Ahmed A; Watson, Jamie N; Schröder, Martin

    2016-06-15

    Accumulation of unfolded proteins in the endoplasmic reticulum (ER) activates the unfolded protein response (UPR). In mammalian cells, UPR signals generated by several ER-membrane-resident proteins, including the bifunctional protein kinase endoribonuclease IRE1α, control cell survival and the decision to execute apoptosis. Processing of XBP1 mRNA by the RNase domain of IRE1α promotes survival of ER stress, whereas activation of the mitogen-activated protein kinase JNK family by IRE1α late in the ER stress response promotes apoptosis. Here, we show that activation of JNK in the ER stress response precedes activation of XBP1. This activation of JNK is dependent on IRE1α and TRAF2 and coincides with JNK-dependent induction of expression of several antiapoptotic genes, including cIap1 (also known as Birc2), cIap2 (also known as Birc3), Xiap and Birc6 ER-stressed Jnk1(-/-) Jnk2(-/-) (Mapk8(-/-) Mapk9(-/-)) mouse embryonic fibroblasts (MEFs) display more pronounced mitochondrial permeability transition and increased caspase 3/7 activity compared to wild-type MEFs. Caspase 3/7 activity is also elevated in ER-stressed cIap1(-/-) cIap2(-/-) and Xiap(-/-) MEFs. These observations suggest that JNK-dependent transcriptional induction of several inhibitors of apoptosis contributes to inhibiting apoptosis early in the ER stress response. PMID:27122189

  13. 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

  14. A smart fluorescence nanoprobe for the detection of cellular alkaline phosphatase activity and early osteogenic differentiation.

    PubMed

    Cao, Feng-Yi; Fan, Jin-Xuan; Long, Yue; Zeng, Xuan; Zhang, Xian-Zheng

    2016-07-01

    In the past decades, biomaterials were designed to induce stem cell toward osteogenic differentiation. However, conventional methods for evaluation osteogenic differentiation all required a process of cell fixation or lysis, which induce waste of a large number of cells. In this study, a fluorescence nanoprobe was synthesized by combining phosphorylated fluoresceinamine isomer I (FLA) on the surface of mesoporous silica-coated superparamagnetic iron oxide (Fe3O4@mSiO2) nanoparticles. In the presence of alkaline phosphatase (ALP), the phosphorylated FLA on the nanoprobe would be hydrolyzed, resulting in a fluorescence recovery of FLA. During early osteogenic differentiation, a high-level expression of cellular ALP was induced, which accelerated the hydrolysis of phosphorylated FLA, resulting in an enhancement of cellular fluorescence intensity. This fluorescence nanoprobe provides us a rapid and non-toxic method for the detection of cellular ALP activity and early osteogenic differentiation. PMID:26961462

  15. The Early Time Properties of GRBs - Canonical Afterglows and the Importance of Prolonged Central Engine Activity

    SciTech Connect

    Melandri, A.; Mundell, C. G.; Kobayashi, S.; Bersier, D.; Steele, I. A.; Smith, R. J.; Carter, D.; Bode, M. F.; Guidorzi, C.; Gomboc, A.

    2009-05-25

    Using a new, comprehensive multiwavelength survey of 63 Gamma Ray Bursts (GRBs) with unprecedented temporal coverage, we classify the observed afterglows into four main classes and discuss the underlying physics that can explain them. The presence or absence of temporal breaks in X-ray and optical bands is used to examine the emission in the context of the standard model; a number of GRBs are shown to deviate from the forward shock model even with the inclusion of energy injection or ambient density gradients. We show that additional emission in the early-time X-ray afterglow due to late-time central engine activity is key and may explain both GRBs whose afterglows do not fit the standard model and those GRBs that appear to be optically dark even at early times.

  16. 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.

  17. The 6-Aminoquinolone WC5 Inhibits Human Cytomegalovirus Replication at an Early Stage by Interfering with the Transactivating Activity of Viral Immediate-Early 2 Protein ▿ †

    PubMed Central

    Loregian, Arianna; Mercorelli, Beatrice; Muratore, Giulia; Sinigalia, Elisa; Pagni, Silvana; Massari, Serena; Gribaudo, Giorgio; Gatto, Barbara; Palumbo, Manlio; Tabarrini, Oriana; Cecchetti, Violetta; Palù, Giorgio

    2010-01-01

    WC5 is a 6-aminoquinolone that potently inhibits the replication of human cytomegalovirus (HCMV) but has no activity, or significantly less activity, against other herpesviruses. Here we investigated the nature of its specific anti-HCMV activity. Structure-activity relationship studies on a small series of analogues showed that WC5 possesses the most suitable pattern of substitutions around the quinolone scaffold to give potent and selective anti-HCMV activity. Studies performed to identify the possible target of WC5 indicated that it prevents viral DNA synthesis but does not significantly affect DNA polymerase activity. In yield reduction experiments with different multiplicities of infection, the anti-HCMV activity of WC5 appeared to be highly dependent on the viral inoculum, suggesting that WC5 may act at an initial stage of virus replication. Consistently, time-of-addition and time-of-removal studies demonstrated that WC5 affects a phase of the HCMV replicative cycle that precedes viral DNA synthesis. Experiments to monitor the effects of the compound on virus attachment and entry showed that it does not inhibit either process. Evaluation of viral mRNA and protein expression revealed that WC5 targets an event of the HCMV replicative cycle that follows the transcription and translation of immediate-early genes and precedes those of early and late genes. In cell-based assays to test the effects of WC5 on the transactivating activity of the HCMV immediate-early 2 (IE2) protein, WC5 markedly interfered with IE2-mediated transactivation of viral early promoters. Finally, WC5 combined with ganciclovir in checkerboard experiments exhibited highly synergistic activity. These findings suggest that WC5 deserves further investigation as a candidate anti-HCMV drug with a novel mechanism of action. PMID:20194695

  18. Physical activity and sedentary behavior during the early years in Canada: a cross-sectional study

    PubMed Central

    2013-01-01

    Background Physical activity and sedentary behavior habits are established during early childhood, yet only recently has objectively measured data been available on children aged 5 years and younger. This study presents data on the physical activity and sedentary behaviors of Canadian children aged 3–5 years. Methods Data were collected as part of the Canadian Health Measures Survey between 2009 and 2011. A nationally-representative sample (n = 459) of children aged 3–5 years wore Actical accelerometers during their waking hours for 7 consecutive days. Data were collected in 60-sec epochs and respondents with ≥4 valid days were retained for analysis. Parents reported their child’s physical activity and screen time habits in a questionnaire. Results Eighty-four percent of 3–4 year old children met the physical activity guideline of 180 minutes of total physical activity every day while 18% met the screen time target of <1 hour per day. Fourteen percent of 5 year old children met the physical activity guideline of 60 minutes of daily moderate-to-vigorous physical activity (MVPA) while 81% met the screen time target of <2 hours per day. Children aged 3–4 years accumulated an average of 352 min/d of total physical activity and 66 minutes of MVPA while 5 year old children accumulated an average of 342 min/d of total physical activity and 68 minutes of MVPA. Children were sedentary for approximately half of their waking hours and spent an average of 2 hours per day in front of screens. Only 15% of 3–4 year olds and 5% of 5 year olds are meeting both the physical activity and sedentary behavior guidelines. Conclusions Promoting physical activity while reducing sedentary behavior is important at all stages of life. The findings of the present study indicate that there remains significant room for improvement in these behaviors among young Canadian children. PMID:23642258

  19. 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. PMID:8687376

  20. 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. PMID:27006973

  1. Early Endosomal Antigen 1 (EEA1) Is an Obligate Scaffold for Angiotensin II-induced, PKC-α-dependent Akt Activation in Endosomes*

    PubMed Central

    Nazarewicz, Rafal Robert; Salazar, Gloria; Patrushev, Nikolay; Martin, Alejandra San; Hilenski, Lula; Xiong, Shiqin; Alexander, R. Wayne

    2011-01-01

    Akt/protein kinase B (PKB) activation/phosphorylation by angiotensin II (Ang II) is a critical signaling event in hypertrophy of vascular smooth muscle cells (VSMCs). Conventional wisdom asserts that Akt activation occurs mainly in plasma membrane domains. Recent evidence that Akt activation may take place within intracellular compartments challenges this dogma. The spatial identity and mechanistic features of these putative signaling domains have not been defined. Using cell fractionation and fluorescence methods, we demonstrate that the early endosomal antigen-1 (EEA1)-positive endosomes are a major site of Ang II-induced Akt activation. Akt moves to and is activated in EEA1 endosomes. The expression of EEA1 is required for phosphorylation of Akt at both Thr-308 and Ser-473 as well as for phosphorylation of its downstream targets mTOR and S6 kinase, but not for Erk1/2 activation. Both Akt and phosphorylated Akt (p-Akt) interact with EEA1. We also found that PKC-α is required for organizing Ang II-induced, EEA1-dependent Akt phosphorylation in VSMC early endosomes. EEA1 expression enables PKC-α phosphorylation, which in turn regulates Akt upstream signaling kinases, PDK1 and p38 MAPK. Our results indicate that PKC-α is a necessary regulator of EEA1-dependent Akt signaling in early endosomes. Finally, EEA1 down-regulation or expression of a dominant negative mutant of PKC-α blunts Ang II-induced leucine incorporation in VSMCs. Thus, EEA1 serves a novel function as an obligate scaffold for Ang II-induced Akt activation in early endosomes. PMID:21097843

  2. 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

  3. Shape-specific activation of occipital cortex in an early blind echolocation expert.

    PubMed

    Arnott, Stephen R; Thaler, Lore; Milne, Jennifer L; Kish, Daniel; Goodale, Melvyn A

    2013-04-01

    We have previously reported that an early-blind echolocating individual (EB) showed robust occipital activation when he identified distant, silent objects based on echoes from his tongue clicks (Thaler, Arnott, & Goodale, 2011). In the present study we investigated the extent to which echolocation activation in EB's occipital cortex reflected general echolocation processing per se versus feature-specific processing. In the first experiment, echolocation audio sessions were captured with in-ear microphones in an anechoic chamber or hallway alcove as EB produced tongue clicks in front of a concave or flat object covered in aluminum foil or a cotton towel. All eight echolocation sessions (2 shapes×2 surface materials×2 environments) were then randomly presented to him during a sparse-temporal scanning fMRI session. While fMRI contrasts of chamber versus alcove-recorded echolocation stimuli underscored the importance of auditory cortex for extracting echo information, main task comparisons demonstrated a prominent role of occipital cortex in shape-specific echo processing in a manner consistent with latent, multisensory cortical specialization. Specifically, relative to surface composition judgments, shape judgments elicited greater BOLD activity in ventrolateral occipital areas and bilateral occipital pole. A second echolocation experiment involving shape judgments of objects located 20° to the left or right of straight ahead activated more rostral areas of EB's calcarine cortex relative to location judgments of those same objects and, as we previously reported, such calcarine activity was largest when the object was located in contralateral hemispace. Interestingly, other echolocating experts (i.e., a congenitally blind individual in Experiment 1, and a late blind individual in Experiment 2) did not show the same pattern of feature-specific echo-processing calcarine activity as EB, suggesting the possible significance of early visual experience and early

  4. 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

  5. Early visual deprivation from congenital cataracts disrupts activity and functional connectivity in the face network.

    PubMed

    Grady, Cheryl L; Mondloch, Catherine J; Lewis, Terri L; Maurer, Daphne

    2014-05-01

    The development of the face-processing network has been examined with functional neuroimaging, but the effect of visual deprivation early in life on this network is not known. We examined this question in a group of young adults who had been born with dense, central cataracts in both eyes that blocked all visual input to the retina until the cataracts were removed during infancy. We used functional magnetic resonance imaging to examine regions in the "core" and "extended" face networks as participants viewed faces and other objects, and performed a face discrimination task. This task required matching faces on the basis of facial features or on the spacing between the facial features. The Cataract group (a) had reduced discrimination performance on the Spacing task relative to Controls; (b) used the same brain regions as Controls when passively viewing faces or making judgments about faces, but showed reduced activation during passive viewing of faces, especially in extended face-network regions; and (c) unlike Controls, showed activation in face-network regions for objects. In addition, the functional connections of the fusiform gyri with the rest of the face network were altered, and these brain changes were related to Cataract participants' performance on the face discrimination task. These results provide evidence that early visual input is necessary to set up or preserve activity and functional connectivity in the face-processing network that will later mediate expert face processing. PMID:24657305

  6. 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

  7. 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

  8. Amino Acid Utilization in Seeds of Loblolly Pine during Germination and Early Seedling Growth (I. Arginine and Arginase Activity).

    PubMed Central

    King, J. E.; Gifford, D. J.

    1997-01-01

    The mobilization and utilization of the major storage proteins in loblolly pine (Pinus taeda L.) seeds following imbibition were investigated. Most of the seed protein reserves were contained within the megagametophyte. Breakdown of these proteins occurred primarily following radicle emergence and correlated with a substantial increase in the free amino acid pool in the seedling; the majority of this increase appeared to be the result of export from the megagametophyte. The megagametophyte was able to break down storage proteins and export free amino acids in the absence of the seedling. Arginine (Arg) was the most abundant amino acid among the principal storage proteins of the megagametophyte and was a major component of the free amino acid pools in both the seedling and the megagametophyte. The increase in free Arg coincided with a marked increase in arginase activity, mainly localized within the cotyledons and epicotyl of the seedling. Arginase activity was negligible in isolated seedlings. Experiments with phenylphosphorodiamidate, a urease inhibitor, supported the hypothesis that arginase participates in Arg metabolism in the seedling. The results of this study indicate that Arg could play an important role in the nutrition of loblolly pine during early seedling growth. PMID:12223664

  9. 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.

  10. 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…

  11. 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,…

  12. Renin-Angiotensin Activation and Oxidative Stress in Early Heart Failure with Preserved Ejection Fraction

    PubMed Central

    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 (Eh GSH) and cysteine (Eh 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 Eh 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 Eh 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

  13. 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

  14. Early detection of human focal seizures based on cortical multiunit activity.

    PubMed

    Park, Yun S; Hochberg, Leigh R; Eskandar, Emad N; Cash, Sydney S; Truccolo, Wilson

    2014-01-01

    Approximately 50 million people in the world suffer from epileptic seizures. Reliable early seizure detection could bring significantly beneficial therapeutic alternatives. In recent decades, most approaches have relied on scalp EEG and intracranial EEG signals, but practical early detection for closed-loop seizure control remains challenging. In this study, we present preliminary analyses of an early detection approach based on intracortical neuronal multiunit activity (MUA) recorded from a 96-microelectrode array (MEA). The approach consists of (1) MUA detection from broadband field potentials recorded at 30 kHz by the MEA; (2) MUA feature extraction; (3) cost-sensitive support vector machine classification of ictal and interictal samples; and (4) Kalman-filtering postprocessing. MUA was here defined as the number of threshold crossing (spike counts) applied to the 300 Hz-6 kHz bandpass filtered local field potentials in 0.1 sec time windows. MUA features explored in this study included the mean, variance, and Fano-factor, computed across the MEA channels. In addition, we used the leading eigenvalues of MUA spatial and temporal correlation matrices computed in 1-sec moving time windows. We assessed the seizure detection approach on out-of-sample data from one-participant recordings with six seizure events and 4.73-hour interictal data. The proposed MUA-based detection approach yielded a 100% sensitivity (6/6) and no false positives, and a latency of 4.17 ± 2.27 sec (mean ± SD) with respect to ECoG-identified seizure onsets. These preliminary results indicate intracortical MUA may be a useful signal for early detection of human epileptic seizures. PMID:25571313

  15. Efficacy of SLZ and MTX (alone or combination) on the treatment of active sacroiliitis in early AS.

    PubMed

    Kabasakal, Yasemin; Kitapcioglu, Gul; Yargucu, Figen; Taylan, Ali; Argin, Mehmet; Gumusdis, Gurbuz

    2009-10-01

    Sacroiliitis is an important sign of spondylarthritis (SpA) of which the prototype disease is ankylosing spondylitis. The radiographic changes required for diagnosing AS occur as late as 8-11 years after the onset of clinical symptoms. Nonsteroid anti-inflammatory drugs (NSAIDs) have been the main treatment for spondylitis of AS. For patients refractory or intolerant to NSAIDs, disease-modifying antirheumatic drugs (DMARDs) have been used as a second-line approach. Sulphasalazine (SLZ) is known as the best DMARD in treatment of peripheral arthritis; also methotrexate (MTX) is currently one of the most widely used DMARDs. But there was no objective information about inflammation of sacroiliac joints during treatment with these DMARDS that are the first places of the beginning point of SpA. For this purpose, in this study, the effect of SLZ and MTX, which are used alone and combination in 6 months, on treatment of active sacroiliitis, which is shown by dynamic magnetic resonance and acute phase reactants in laboratory has been investigated. 55 patients (F:M = 34:21) with active sacroiliitis [mean age = 37.05 + 13.03 year (n = 55)] were evaluated and determined by dynamic magnetic resonance imaging in this study. The better response in the SLZ treatment group than the other two groups has been obtained. Nevertheless, those changes were not statistically found different. In conclusion, the ratio of treatment of active sacroiliitis, especially early period, with SLZ as a DMARD is better than MTX or MTX + SLZ, but this difference is not statistically significant. A prospective study of the treatment of active sacroiliitis by DMARDs may be more illustrative. PMID:19593568

  16. 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.

  17. 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

  18. 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

  19. 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

  20. The majority of early primordial germ cells acquire pluripotency by AKT activation.

    PubMed

    Matsui, Yasuhisa; Takehara, Asuka; Tokitake, Yuko; Ikeda, Makiko; Obara, Yuka; Morita-Fujimura, Yuiko; Kimura, Tohru; Nakano, Toru

    2014-12-01

    Primordial germ cells (PGCs) are undifferentiated germ cells in embryos, the fate of which is to become gametes; however, mouse PGCs can easily be reprogrammed into pluripotent embryonic germ cells (EGCs) in culture in the presence of particular extracellular factors, such as combinations of Steel factor (KITL), LIF and bFGF (FGF2). Early PGCs form EGCs more readily than do later PGCs, and PGCs lose the ability to form EGCs by embryonic day (E) 15.5. Here, we examined the effects of activation of the serine/threonine kinase AKT in PGCs during EGC formation; notably, AKT activation, in combination with LIF and bFGF, enhanced EGC formation and caused ∼60% of E10.5 PGCs to become EGCs. The results indicate that the majority of PGCs at E10.5 could acquire pluripotency with an activated AKT signaling pathway. Importantly, AKT activation did not fully substitute for bFGF and LIF, and AKT activation without both LIF and bFGF did not result in EGC formation. These findings indicate that AKT signal enhances and/or collaborates with signaling pathways of bFGF and of LIF in PGCs for the acquisition of pluripotency. PMID:25359722

  1. Nrf2 Activation Promotes Keratinocyte Survival during Early Skin Carcinogenesis via Metabolic Alterations.

    PubMed

    Rolfs, Frank; Huber, Marcel; Kuehne, Andreas; Kramer, Stefan; Haertel, Eric; Muzumdar, Sukalp; Wagner, Johanna; Tanner, Yasmine; Böhm, Friederike; Smola, Sigrun; Zamboni, Nicola; Levesque, Mitchell P; Dummer, Reinhard; Beer, Hans-Dietmar; Hohl, Daniel; Werner, Sabine; Schäfer, Matthias

    2015-11-15

    Pharmacologic activation of the transcription factor NRF2 has been suggested to offer a strategy for cancer prevention. In this study, we present evidence from murine tumorigenesis experiments suggesting there may be limitations to this possibility, based on tumorigenic effects of Nrf2 in murine keratinocytes that have not been described previously. In this setting, Nrf2 expression conferred metabolic alterations in keratinocytes that were protumorigenic in nature, affecting enzymes involved in glutathione biosynthesis or in the oxidative pentose phosphate pathway and other NADPH-producing enzymes. Under stress conditions, coordinate increases in NADPH, purine, and glutathione levels promoted the survival of keratinocytes harboring oncogenic mutations, thereby promoting tumor development. The protumorigenic activity of Nrf2 in keratinocytes was particularly significant in a mouse model of skin tumorigenesis that did not rely upon chemical carcinogenesis. In exploring the clinical relevance of our findings, we confirm that NRF2 and protumorigenic NRF2 target genes were activated in some actinic keratoses, the major precancerous lesion in human skin. Overall, our results reveal an unexpected tumor-promoting activity of activated NRF2 during early phases of skin tumorigenesis. PMID:26530903

  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. 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. PMID:25620909

  4. 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

  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. PMID:24937713

  6. 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

  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. Expression of early activation antigen (CD69) during human thymic development.

    PubMed Central

    Jung, L K; Haynes, B F; Nakamura, S; Pahwa, S; Fu, S M

    1990-01-01

    The novel early activation antigen, EA1, has been shown to be induced by mitogens, antigens and the tumour promoter, phorbol myristate acetate (PMA), on human lymphocytes. This antigen has been designated to be CD69. EA1 has also been shown to be expressed on thymocytes without exogenous activation stimuli. In order to characterize further the expression of EA1 on thymocytes, the ontogeny of its expression was studied. EA1 appeared between 7 and 9.5 weeks of gestation, after colonization of the thymic rudiment with CD7+ T cell precursors, but before the onset of compartmentalization of the thymus into cortical and medullary zones. After cortico-medullary differentiation, the majority of medullary thymocytes expressed EA1 while only a fraction of the cortical thymocytes expressed this antigen. In the fetal and post-natal cortex, EA1 expression appeared to cluster in the subcapsular cortex. EA1+ cells were also scattered throughout the inner cortex. By two-colour fluorocytometric analysis of post-natal thymocytes, it was shown that EA1 was expressed on 30 to 65% of thymocytes. EA1 was expressed on CD4+ CD8+ as well as on the more immature CD4- CD8- thymocytes. In contrast to circulating T cells, thymocytes were much less responsive to PMA stimulation for the expression of EA1. Molecular characterization showed that EA1 on thymocytes had the same structure as that of activated peripheral T cells. In addition, thymic EA1 was constitutively phosphorylated. Thus, EA1 expression is acquired early during thymic development after colonization of the thymic rudiment by CD7+ T cell precursors. However, the specific role that EA1 may play in the activation and function of developing thymocytes remains to be determined. Images Fig. 7 Fig. 8 PMID:2204504

  9. 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

  10. Impacts of early intervention with fluoxetine following early neonatal immune activation on depression-like behaviors and body weight in mice.

    PubMed

    Doosti, Mohammad-Hossein; Bakhtiari, Amir; Zare, Payman; Amani, Mohammad; Majidi-Zolbanin, Naime; Babri, Shirin; Salari, Ali-Akbar

    2013-06-01

    Several reports have suggested that early neonatal immune activation adversely influences the hypothalamic-pituitary-adrenal (HPA) axis development in humans and animal models. In addition, there have been several studies indicating that early intervention with fluoxetine (FLX) can alter HPA axis development and function, and prevent occurrence of behavioral abnormalities induced by common early-life insults. The present study aims to investigate the effects of early intervention with FLX following early neonatal immune activation on depression-like behaviors and body weight in mice. Neonatal mice in their postnatal days (PNDs) 3 and 5 received either lipopolysaccharide (LPS; 50 μg/kg, s.c.) or saline treatment, then male and female mice of both neonatal intervention groups received oral administration of FLX (5 and 10 mg/kg/day) or water via regular drinking bottles during the periadolescent period (PNDs 35-65). The results showed that neonatal LPS exposure elevated depression-like behaviors accompanied by increasing corticosterone levels in adulthood and decreasing body weight during neonatal and adolescent periods. Furthermore, the periadolescent FLX treatment inhibited the depression-like behaviors induced by neonatal infection in both sexes. This study obtained some experimental evidence indicating the potential adverse impacts of the FLX on normal behavioral development in male control animals. In conclusion, our findings suggest that an early pharmacological intervention with FLX may prevent emergence of depression-like behaviors induced by neonatal immune challenge without any detrimental effect on health in a sex- and dose-dependent manner in mice. PMID:23270703

  11. 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

  12. 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

  13. Vestibular Activation Differentially Modulates Human Early Visual Cortex and V5/MT Excitability and Response Entropy

    PubMed Central

    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. PMID:22291031

  14. 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

  15. 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

  16. 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

  17. Canonical Wnt Signaling Activity in Early Stages of Chick Lung Development

    PubMed Central

    daMota, Paulo; Correia-Pinto, Jorge

    2014-01-01

    Wnt signaling pathway is an essential player during vertebrate embryonic development which has been associated with several developmental processes such as gastrulation, body axis formation and morphogenesis of numerous organs, namely the lung. Wnt proteins act through specific transmembrane receptors, which activate intracellular pathways that regulate cellular processes such as cell proliferation, differentiation and death. Morphogenesis of the fetal lung depends on epithelial-mesenchymal interactions that are governed by several growth and transcription factors that regulate cell proliferation, fate, migration and differentiation. This process is controlled by different signaling pathways such as FGF, Shh and Wnt among others. Wnt signaling is recognized as a key molecular player in mammalian pulmonary development but little is known about its function in avian lung development. The present work characterizes, for the first time, the expression pattern of several Wnt signaling members, such as wnt-1, wnt-2b, wnt-3a, wnt-5a, wnt-7b, wnt-8b, wnt-9a, lrp5, lrp6, sfrp1, dkk1, β-catenin and axin2 at early stages of chick lung development. In general, their expression is similar to their mammalian counterparts. By assessing protein expression levels of active/total β-catenin and phospho-LRP6/LRP6 it is revealed that canonical Wnt signaling is active in this embryonic tissue. In vitro inhibition studies were performed in order to evaluate the function of Wnt signaling pathway in lung branching. Lung explants treated with canonical Wnt signaling inhibitors (FH535 and PK115-584) presented an impairment of secondary branch formation after 48 h of culture along with a decrease in axin2 expression levels. Branching analysis confirmed this inhibition. Wnt-FGF crosstalk assessment revealed that this interaction is preserved in the chick lung. This study demonstrates that Wnt signaling is crucial for precise chick lung branching and further supports the avian lung as a good

  18. 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

  19. 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. PMID:27143046

  20. Early warning signs of bulking in an activated sludge system through interpretation of ATP data in a systems analysis context.

    PubMed

    Brault, Jean-Martin; Whalen, Pat; Stuart, Paul

    2011-10-01

    A research project was undertaken at an integrated thermomechanical pulp and paper mill in Canada to evaluate the use of adenosine triphosphate (ATP) monitoring methods in order to identify the potential for operational problems related to microbiological aspects of activated sludge. The specific filamentous bulking ATP (fbATP) ratio is an emerging measurement technique that measures the proportion of flocs that have bulking potential by filtering a sample through a 250 microm mesh and measuring the ATP in the retentate. For the host mill in this study, the specific fbATP measurement provides early warning signs of bulking, at 1.0 to 1.5 times the sludge age, before poor settling occurs. A possible bulking scenario was identified in which the initiator was the overflow of an upstream tank containing high BOD whitewater, resulting in spikes of organic acids to the treatment and promoting the proliferation of certain types of filamentous bacteria. A storage response by filamentous bacteria to these high readily biodegradable substrate conditions was monitored with fbATP. By predicting the onset of bulking conditions, this technique can potentially assist operators to make corrective actions proactively. PMID:22329156

  1. Plasma rennin activity: Early indicator of renal injury in bilateral pelviureteric junction obstruction in children

    PubMed Central

    Singh, Amit; Bajpai, Minu

    2014-01-01

    Objective: The objective of the present study is to analyze the early indicators of renal injury in children with bilateral pelviuretric junction obstruction. Materials and Methods: We investigated 23 children, 46 kidney units who were diagnosed with bilateral pelvi-ureteric junction obstruction (PUJO) and underwent unilateral or bilateral pyeloplasty between January 2001 and December 2011. Ipsilateral kidney biopsy was performed during pyeloplasty. Kidney biopsy results were divided into three categories. Pre-operative investigation included ultrasonography with the Society of Fetal Urology (SFU) grading, plasma rennin activity (PRA) and differential renal function (DRF). Results: Out of 23 children there were 17 (73.9%) boys while 6 (26.1%) girls. Median age at operation was 35.4 months (range: 9-60 months). Unilateral pyeloplasty was performed in 14 (60.8%), simultaneous bilateral pyeloplasty in 2 (8.6%) and sequential bilateral pyeloplasty in 7 (30.4%). Conclusion: In bilateral PUJO where DRF and SFU grading of hydronephrosis did not correctly reflect renal injury, PRA showed a significant relationship with renal histopathologic grade and could be an early indicator of renal injury in bilateral PUJO. PMID:25371604

  2. 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

  3. 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.

  4. Genes of phenylpropanoid pathway are activated in early response to Fusarium attack in flax plants.

    PubMed

    Kostyn, Kamil; Czemplik, Magdalena; Kulma, Anna; Bortniczuk, Małgorzata; Skała, Jacek; Szopa, Jan

    2012-07-01

    Fusarium is the most common flax pathogen causing serious plant diseases and in most cases leading to plant death. To protect itself, the plant activates a number of genes and metabolic pathways, both to counteract the effects of the pathogen, and to eliminate the threat. The identification of the plant genes which respond to infection is the approach, that has been used in this study. Forty-seven flax genes have been identified by means of cDNA subtraction method as those, which respond to pathogen infection. Subtracted genes were classified into several classes and the prevalence of the genes involved in the broad spectrum of antioxidants biosynthesis has been noticed. By means of semi-quantitative RT-PCR and metabolite profiling, the involvement of subtracted genes controlling phenylpropanoid pathway in flax upon infection was positively verified. We identified the key genes of the synthesis of these compounds. At the same time we determined the level of the metabolites produced in the phenylpropanoid pathway (flavonoids, phenolic acids) in early response to Fusarium attack by means of GC-MS technique. To the best of our knowledge this is the first report to describe genes and metabolites of early flax response to pathogens studied in a comprehensive way. PMID:22608524

  5. 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

  6. 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.

  7. 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.

  8. Active-sterile neutrino oscillations in the early universe with dynamical neutrino asymmetries

    NASA Astrophysics Data System (ADS)

    Saviano, Ninetta

    2013-04-01

    In the last recent years different anomalies observed in short-baseline neutrino oscillation experiments seem to point towards the existence of light sterile neutrinos. These sterile neutrinos can also be produced in the early universe by oscillations of the active neutrinos and can affect different cosmological observables. In order to quantify the abundance of sterile neutrinos, we perform a detailed study of the flavor evolution in (3+1) and (2+1) oscillation schemes, in presence of dynamical primordial neutrino asymmetries L. We find that for |L|≲10-4 eV sterile neutrinos would be completely thermalized creating a tension with the cosmological data. An asymmetry of |L|≳10-3 is then required in order to suppress the sterile production and to reconcile them with cosmology.

  9. 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. PMID:26415918

  10. 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. PMID:25684369

  11. Active-sterile neutrino oscillations in the early Universe with full collision terms

    NASA Astrophysics Data System (ADS)

    Hannestad, Steen; Sloth Hansen, Rasmus; Tram, Thomas; Wong, Yvonne Y. Y.

    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.

  12. 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

  13. 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.

  14. 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

  15. New insights into the early biochemical activation of jasmonic acid biosynthesis in leaves.

    PubMed

    Bonaventure, Gustavo; Baldwin, Ian T

    2010-03-01

    In plants, herbivore attack elicits the rapid accumulation of jasmonic acid (JA) which results from the activation of constitutively expressed biosynthetic enzymes. The molecular mechanisms controlling the activation of JA biosynthesis remain largely unknown however new research has elucidated some of the early regulatory components involved in this process. Nicotiana attenuata plants, a wild tobacco species, responds to fatty acid amino acid conjuguates (FAC) elicitors in the oral secretion of its natural herbivore, Manduca sexta, by triggering specific defense and tolerance responses against it; all of the defense responses known to date require the amplification of the wound-induced JA increase. We recently demonstrated that this FAC-elicited JA burst requires an increased flux of free linolenic acid (18:3) likely originating from the activation of a plastidial glycerolipase (GLA1) which is activated by an abundant FAC found in insect oral secretions, N-linolenoyl-glutamate (18:3-Glu). The lack of accumulation of free 18:3 after elicitation suggests a tight physical association between GLA1 and LOX3 in N. attenuata leaves. In addition, the salicylate-induced protein kinase (SIPK) and the nonexpressor of PR-1 (NPR1) participate in this activation mechanism that controls the supply of 18:3. In contrast, the wound-induced protein kinase (WIPK) does not but instead regulates the conversion of 13(S)-hydroperoxy-18:3 into 12-oxo-phytodienoic acid (OPDA). These results open new perspectives on the complex network of signals and regulatory components inducing the JA biosynthetic pathway. PMID:20037473

  16. Monitoring brain activation changes in the early postoperative period after radical prostatectomy using fMRI.

    PubMed

    Seseke, S; Baudewig, J; Ringert, R-H; Rebmann, U; Dechent, P

    2013-09-01

    Urinary incontinence is a major concern following radical prostatectomy. The etiology is multifactorial involving intrinsic sphincter deficiency and/or detrusor hyperactivity and/or decreased bladder compliance. Recent studies employing functional imaging methodology nicely demonstrated the reference regions of the micturition circuit. Based on these landmarks this work complements this field of research by studying patients with bladder dysfunction. Our aim was to evaluate, whether iatrogenic impairment of the pelvic floor muscles after retropubic radical prostatectomy (RRP) causes detectable changes in fMRI in the early postoperative period. fMRI was performed at 3T in 22 patients before and after RRP with urge to void due to a filled bladder. In a non-voiding model they were instructed to contract or to relax the pelvic floor muscles repetitively. As previously reported in healthy men, contraction and relaxation of pelvic floor muscles induced strong activations in the brainstem and more rostral areas in our group of patients before and after RRP. In general, all of them had stronger activations during contraction than during relaxation in all regions before and after the operation. Even though there was no difference in the activation level when relaxing the pelvic floor before and after the operation, we found stronger activation during contraction when comparing the preoperative with the postoperative level in some of the regions. The results suggest that the same cortical and subcortical networks can be demonstrated for micturition control in patients with prostate cancer as in healthy subjects. However, impaired pelvic floor muscle function after RRP seems to induce different activation intensities. PMID:23583743

  17. Evaluation of an oral telomerase activator for early age-related macular degeneration - a pilot study

    PubMed Central

    Dow, Coad Thomas; Harley, Calvin B

    2016-01-01

    Purpose Telomere attrition and corresponding cellular senescence of the retinal pigment epithelium contribute to the changes of age-related macular degeneration. Activation of the enzyme telomerase can add telomeric DNA to retinal pigment epithelium chromosomal ends and has been proposed as a treatment for age-related macular degeneration. We report the use of a small molecule, oral telomerase activator (TA)-65 in early macular degeneration. This study, focusing on early macular degeneration, provides a model for the use of TAs in age-related disease. Method Thirty-eight (38) patients were randomly assigned to a 1-year, double-blinded, placebo-controlled interventional study with arms for oral TA-65 or placebo. Macular functions via micro-perimetry were the primary measured outcomes. Results The macular function in the arm receiving the TA-65 showed significant improvement relative to the placebo control. The improvement was manifest at 6 months and was maintained at 1 year: macular threshold sensitivity (measured as average dB [logarithmic decibel scale of light attenuation]) improved 0.97 dB compared to placebo (P-value 0.02) and percent reduced thresholds lessened 8.2% compared to the placebo arm (P-value 0.04). Conclusion The oral TA significantly improved the macular function of treatment subjects compared to controls. Although this study was a pilot and a larger study is being planned, it is noteworthy in that it is, to our knowledge, the first randomized placebo-controlled study of a TA supplement. PMID:26869760

  18. Normal and Mutant Rhodopsin Activation Measured with the Early Receptor Current in a Unicellular Expression System

    PubMed Central

    Shukla, Pragati; Sullivan, Jack M.

    1999-01-01

    The early receptor current (ERC) represents molecular charge movement during rhodopsin conformational dynamics. To determine whether this time-resolved assay can probe various aspects of structure–function relationships in rhodopsin, we first measured properties of expressed normal human rhodopsin with ERC recordings. These studies were conducted in single fused giant cells containing on the order of a picogram of regenerated pigment. The action spectrum of the ERC of normal human opsin regenerated with 11-cis-retinal was fit by the human rhodopsin absorbance spectrum. Successive flashes extinguished ERC signals consistent with bleaching of a rhodopsin photopigment with a normal range of photosensitivity. ERC signals followed the univariance principle since millisecond-order relaxation kinetics were independent of the wavelength of the flash stimulus. After signal extinction, dark adaptation without added 11-cis-retinal resulted in spontaneous pigment regeneration from an intracellular store of chromophore remaining from earlier loading. After the ERC was extinguished, 350-nm flashes overlapping metarhodopsin-II absorption promoted immediate recovery of ERC charge motions identified by subsequent 500-nm flashes. Small inverted R2 signals were seen in response to some 350-nm flashes. These results indicate that the ERC can be photoregenerated from the metarhodopsin-II state. Regeneration with 9-cis-retinal permits recording of ERC signals consistent with flash activation of isorhodopsin. We initiated structure–function studies by measuring ERC signals in cells expressing the D83N and E134Q mutant human rhodopsin pigments. D83N ERCs were simplified in comparison with normal rhodopsin, while E134Q ERCs had only the early phase of charge motion. This study demonstrates that properties of normal rhodopsin can be accurately measured with the ERC assay and that a structure–function investigation of rapid activation processes in analogue and mutant visual pigments is

  19. 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.

  20. Added effects of dexamethasone and mesenchymal stem cells on early Natural Killer cell activation.

    PubMed

    Michelo, Clive M; Fasse, Esther; van Cranenbroek, Bram; Linda, Katrin; van der Meer, Arnold; Abdelrazik, Heba; Joosten, Irma

    2016-07-01

    Graft rejection and graft-versus-host disease are leading causes of transplant related mortality despite advancements in immunosuppressive therapy. Mesenchymal stem cells (MSCs) offer a promising addition to immunosuppressive drugs (ISD), while NK-cells are increasingly used as effector cells in graft-versus-leukemia. Combined therapy of ISD, NK-cells and/or MSCs is used in clinical practice. Here, we examined the effects of MSCs and selected ISD (tacrolimus, cyclosporin A, mycophenolic acid, dexamethasone) treatment on early NK-cell activation. We assessed STAT4 and STAT5 phosphorylation triggered by IL-12 and IL-2, respectively. Furthermore, we determined IFNγ, perforin production and the expression pattern of selected NK-cell receptors. Of all drugs tested, only dexamethasone inhibited NK-cell STAT4 and STAT5 phosphorylation. All ISD, with the exception of MPA, significantly inhibited IFNγ, and only dexamethasone inhibited upregulation of early activation markers CD69 and CD25 (IL-2 condition only). MSCs inhibited IL-2 induced NK cell STAT5 phosphorylation, IFNγ production and CD69 upregulation, and IL-12 induced IFNγ and perforin production. While MSCs mediated inhibition of CD69 expression was cell contact dependent, inhibition of IFNγ and perforin production, as well as STAT5 phosphorylation was cell-contact independent. Importantly, dexamethasone augmented MSCs mediated inhibition of both IL-12 and IL-2 induced CD69 expression and IFNγ production, as well as IL-2 induced STAT5 phosphorylation. Taken together, these novel insights may help the design of future NK-cell and MSCs based immunotherapy. PMID:27142560

  1. TISSUE-PLASMINOGEN ACTIVATOR IS INDUCED AS AN IMMEDIATE-EARLY GENE DURING SEIZURE, KINDLING, AND LONG-TERM POTENTIATION

    EPA Science Inventory

    Activity-dependent genes in brain have been identified using differential screening of hippocampal cDNA library from rats exposed to metrazol seizures under conditions of superconduction. Five immediate early genes whose expression is elevated by neural activity were identified. ...

  2. 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…

  3. 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

  4. TLR9 Activation Dampens the Early Inflammatory Response to Paracoccidioides brasiliensis, Impacting Host Survival

    PubMed Central

    Menino, João Filipe; Saraiva, Margarida; Gomes-Alves, Ana G.; Lobo-Silva, Diogo; Sturme, Mark; Gomes-Rezende, Jéssica; Saraiva, Ana Laura; Goldman, Gustavo H.; Cunha, Cristina; Carvalho, Agostinho; Romani, Luigina; Pedrosa, Jorge; Castro, António Gil; Rodrigues, Fernando

    2013-01-01

    Background Paracoccidioides brasiliensis causes paracoccidioidomycosis, one of the most prevalent systemic mycosis in Latin America. Thus, understanding the characteristics of the protective immune response to P. brasiliensis is of interest, as it may reveal targets for disease control. The initiation of the immune response relies on the activation of pattern recognition receptors, among which are TLRs. Both TLR2 and TLR4 have been implicated in the recognition of P. brasiliensis and regulation of the immune response. However, the role of TLR9 during the infection by this fungus remains unclear. Methodology/Principal findings We used in vitro and in vivo models of infection by P. brasiliensis, comparing wild type and TLR9 deficient (−/−) mice, to assess the contribution of TLR9 on cytokine induction, phagocytosis and outcome of infection. We show that TLR9 recognizes either the yeast form or DNA from P. brasiliensis by stimulating the expression/production of pro-inflammatory cytokines by bone marrow derived macrophages, also increasing their phagocytic ability. We further show that TLR9 plays a protective role early after intravenous infection with P. brasiliensis, as infected TLR9−/− mice died at higher rate during the first 48 hours post infection than wild type mice. Moreover, TLR9−/− mice presented tissue damage and increased expression of several cytokines, such as TNF-α and IL-6. The increased pattern of cytokine expression was also observed during intraperitoneal infection of TLR9−/− mice, with enhanced recruitment of neutrophils. The phenotype of TLR9−/− hosts observed during the early stages of P. brasiliensis infection was reverted upon a transient, 48 hours post-infection, neutrophil depletion. Conclusions/Significance Our results suggest that TLR9 activation plays an early protective role against P. brasiliensis, by avoiding a deregulated type of inflammatory response associated to neutrophils that may lead to tissue damage. Thus

  5. Identifying the target cell in primary simian immunodeficiency virus (SIV) infection: highly activated memory CD4(+) T cells are rapidly eliminated in early SIV infection in vivo.

    PubMed

    Veazey, R S; Tham, I C; Mansfield, K G; DeMaria, M; Forand, A E; Shvetz, D E; Chalifoux, L V; Sehgal, P K; Lackner, A A

    2000-01-01

    It has recently been shown that rapid and profound CD4(+) T-cell depletion occurs almost exclusively within the intestinal tract of simian immunodeficiency virus (SIV)-infected macaques within days of infection. Here we demonstrate (by three- and four-color flow cytometry) that this depletion is specific to a definable subset of CD4(+) T cells, namely, those having both a highly and/or acutely activated (CD69(+) CD38(+) HLA-DR(+)) and memory (CD45RA(-) Leu8(-)) phenotype. Moreover, we demonstrate that this subset of helper T cells is found primarily within the intestinal lamina propria. Viral tropism for this particular cell type (which has been previously suggested by various studies in vitro) could explain why profound CD4(+) T-cell depletion occurs in the intestine and not in peripheral lymphoid tissues in early SIV infection. Furthermore, we demonstrate that an acute loss of this specific subset of activated memory CD4(+) T cells may also be detected in peripheral blood and lymph nodes in early SIV infection. However, since this particular cell type is present in such small numbers in circulation, its loss does not significantly affect total CD4(+) T cell counts. This finding suggests that SIV and, presumably, human immunodeficiency virus specifically infect, replicate in, and eliminate definable subsets of CD4(+) T cells in vivo. PMID:10590091

  6. Immune activation and IL-12 production during acute/early HIV infection in the absence and presence of highly active, antiretroviral therapy.

    PubMed

    Byrnes, Adriana A; Harris, David M; Atabani, Sowsan F; Sabundayo, Beulah P; Langan, Susan J; Margolick, Joseph B; Karp, Christopher L

    2008-12-01

    Suppressed IL-12 production and maladaptive immune activation, both of which are ameliorated by successful highly active antiretroviral therapy (HAART), are thought to play important roles in the immunopathogenesis of chronic HIV infection. Despite the important effects of the immunological and virological events of early HIV infection on subsequent disease progression, IL-12 production and immune activation in early infection remain under-defined. To quantify IL-12 production and immune activation during acute/early HIV infection, in the presence and absence of HAART, we performed a prospective, longitudinal study of participants in the Baltimore site of the Acute Infection and Early Disease Research Program, with cross-sectional comparison to healthy control subjects. PBMC cytokine productive capacity and plasma immune activation markers [soluble CD8 (sCD8), sCD4, granzyme B, neopterin, beta2-microglobulin, sIL-2R, sTNFRI, sTNFRII, and IL-12p70] were quantified by ELISA. Notably, PBMC from patients with acute/early HIV infection exhibited in vivo IL-12p70 production along with increased, maximal in vitro IL-12 production. Further, despite evidence from plasma markers of generalized immune activation, no elevation in plasma levels of sCD4 was observed, suggesting relative blunting of in vivo CD4+ T cell activation from the beginning of HIV infection. Finally, despite successful virological responses to HAART, heightened in vivo CD8+ T cell activation, IL-12 production, and IFN activity were sustained for at least 6 months during primary HIV infection. These data underscore the need for comparative mechanistic analysis of the immunobiology of early and chronic HIV infection. PMID:18806124

  7. 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. PMID:27435419

  8. 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

  9. 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

  10. 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.

  11. 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

  12. Probing the active-site requirements of human intestinal N-terminal maltase glucoamylase: the effect of replacing the sulfate moiety by a methyl ether in ponkoranol, a naturally occurring α-glucosidase inhibitor.

    PubMed

    Eskandari, Razieh; Jones, Kyra; Rose, David R; Pinto, B Mario

    2010-10-01

    Ponkoranol is a naturally occurring glucosidase inhibitor isolated from the plant Salacia reticulata. The compound comprises a sulfonium ion with an internal sulfate counter ion. We report here an efficient synthetic route to 3'-O-methyl ponkoranol to test the hypothesis that occupation of a hydrophobic pocket by a methyl group instead of the polar sulfate ion within the active site of human N-terminal maltase glucoamylase would be beneficial. The synthetic strategy relies on the nucleophilic attack of 2,3,5-tri-O-benzyl-1,4-anhydro-4-thio-D-arabinitol at the C-6 position of benzyl 6-O-p-toluenesulfonyl β-D-glucopyranoside, followed by deprotection using boron trichloride and reduction with sodium borohydride. The target compound inhibited the N-terminal catalytic domain of intestinal human maltase glucoamylase (ntMGAM) with a K(i) value of 0.50 ± 0.04 μM, higher than those of de-O-sulfonated ponkoranol (K(i)=43 ± 3 nM), or its 5'-stereoisomer (K(i)=15 ± 1 nM). We conclude that the interaction of the methyl group with hydrophobic residues in the active site is not as beneficial to inhibition of ntMGAM as the other interactions of the polyhydroxylated chain with active-site residues. PMID:20801033

  13. 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

  14. 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

  15. Early evolution of an X-ray emitting solar active region

    NASA Technical Reports Server (NTRS)

    Wolfson, C. J.; Acton, L. W.; Leibacher, J. W.; Roethig, D. T.

    1977-01-01

    The birth and early evolution of a solar active region has been investigated using X-ray observations from the mapping X-ray heliometer on board the OSO-8 spacecraft. X-ray emission is observed within three hours of the first detection of H-alpha plage. At that time, a plasma temperature of four million K in a region having a density on the order of 10 to the 10th power per cu cm is inferred. During the fifty hours following birth almost continuous flares or flare-like X-ray bursts are superimposed on a monotonically increasing base level of X-ray emission produced by the plasma. If the X-rays are assumed to result from heating due to dissipation of current systems or magnetic field reconnection, it may be concluded that flare-like X-ray emission soon after active region birth implies that the magnetic field probably emerges in a stressed or complex configuration.

  16. The NASA Soil Moisture Active Passive (SMAP) Mission Status and Early Results

    NASA Astrophysics Data System (ADS)

    Entekhabi, Dara; Yueh, Simon; O'Neill, Peggy E.; Wood, Eric F.; Njoku, Eni G.; Entin, Jared K.; Kellogg, Kent H.

    2015-04-01

    The NASA Soil Moisture Active Passive (SMAP) mission is launched in early 2015. The objective of SMAP is to produce global estimates of surface soil moisture at 9 km resolution every 2-3 days. It will also provide the freeze/thaw state of land surface north of 45° N at better than 3 km resolution every two days. The mission science data products are derived from the L-band radar and radiometer on board the SMAP spacecraft. The radar and radiometer share a rotating 6-meter mesh reflector antenna. The instruments operate on-board the SMAP spacecraft in a 685-km Sun-synchronous near-polar orbit, viewing the surface at a constant 40-degree incidence angle across the wide 1000-km swath. The radiometer includes several capabilities based on characteristics of data over time, frequency band, and polarization to detect anthropogenic Radio-Frequency Interference (RFI). This presentation includes: 1) the status of SMAP mission related to radar and radiometer performance, 2) report on detected RFI environment, 3) calibration activities, and 4) preliminary assessment of soil moisture retrieval, freeze/thaw detection and model value-added (root-zone soil moisture and Net Ecosystem Exchange) algorithms.

  17. Stretch-activated channels in single early distal tubule cells of the frog.

    PubMed Central

    Hurst, A M; Hunter, M

    1990-01-01

    1. Single stretch-activated channels have been studied in cell-attached and excised patches from single early distal tubule (diluting segment) cells of Rana temporaria. 2. The channels can be reversibly activated, in both cell-attached and excised patches, by the application of negative pressure to the pipette causing mechanical stretching of the cell membrane. In cell-attached patches, application of 14.8 cmH2O negative pressure to the patch pipette increased reversibly the open probably from 0.11 to 0.87. 3. The channel conductance in the cell-attached configuration with standard Ringer solution in the pipette is 21.3 pS. 4. The channel is non-specific. In excised inside-out patches ion substitution experiments show that the channel does not discriminate between sodium and potassium ions, nor does it appear to select for cations over anions. 5. The channel is voltage sensitive such that depolarizing the cell opens the channel. The open probability at the resting membrane potential, 0.89, was reduced to 0.26 at a hyperpolarizing potential of 100 mV (holding pressure of -20.1 cmH2O or -206 Pa). 6. The sensitivity of the channel to mechanical stretching suggests that the channel may be involved in cell volume regulation. PMID:1707964

  18. Akt Specific Activator SC79 Protects against Early Brain Injury following Subarachnoid Hemorrhage.

    PubMed

    Zhang, Dingding; Zhang, Huasheng; Hao, Shuangying; Yan, Huiying; Zhang, Zihuan; Hu, Yangchun; Zhuang, Zong; Li, Wei; Zhou, Mengliang; Li, Kuanyu; Hang, Chunhua

    2016-06-15

    A growing body of evidence demonstrates that Akt may serve as a therapeutic target for treatment of early brain injury following subarachnoid hemorrhage (SAH). The purpose of the current study was to evaluate the neuroprotective effect of Akt specific activator SC79 in an experimental rat model of SAH. SAH was induced by injecting 300 μL of blood into the prechiasmatic cistern. Intracerebroventricular (ICV) injection of SC79 (30 min post-SAH) induced the p-Akt (Ser473) expression in a dose-dependent manner. A single ICV dose treatment of SC79 (100 μg/rat) significantly increased the expression of Bcl-2 and p-GSK-3β (Ser9), decreased the protein levels of Bax, cytoplasm cytochrome c, and cleaved caspase-3, indicating the antiapoptotic effect of SC79. As a result, the number of apoptotic cells was reduced 24 h post SAH. Moreover, SC79 treatment alleviated SAH-induced oxidative stress, restored mitochondrial morphology, and improved neurological deficits. Strikingly, treatment of SC79 provided a beneficial outcome against neurologic deficit with a therapeutic window of at least 4 h post SAH by ICV injection and 30 min post SAH by intraperitoneal injection. Collectively, SC79 exerts its neuroprotective effect likely through the dual activities of antioxidation and antiapoptosis. These data provide a basic platform to consider SC79 as a novel therapeutic agent for treatment of SAH. PMID:26983552

  19. 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.

  20. 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

  1. 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.

  2. [Long-term effect of a cognitive intervention on learning and participation in a significant leisure activity in early dementia of Alzheimer type: a case study].

    PubMed

    Provencher, Véronique; Bier, Nathalie; Audet, Thérèse; Gagnon, Lise

    2009-06-01

    Decreased ability to accomplish significant leisure activities often occurs in early stages of dementia of Alzheimer type (DAT). As a long term effect, it may eventually affect the quality of life of the patient as well as that of the caregiver's. In a previous study, a woman with early DAT (77 years old, MMSE: 24/30) improved her participation in 2 leisure activities (listening to music and praying in a group) following the learning of a few tasks (e.g. using a radio cassette, remembering the significance of an pre-programmed ring) as a result of a cognitive intervention. The present study presents the long term effect of this intervention on the retention of the learned tasks and on spontaneous participation in both leisure activities of her daily living. Measures of tasks' learning and spontaneous participation in activities have been obtained through direct observation (ex: ability to use the tasks learned without assistance) and telephone conversations with the caregiver. The measures were taken 9 to 15 months post-intervention. Nine months after the end of the intervention, the participant could no longer use the radio cassette, but was able to remember the significance of the pre-programmed ring. Similarly, she stopped listening to music, but still attended her prayer group. The intervention appears to maintain participation in a leisure activity for several months in a patient with early DAT, in spite of expected functional decline. This functional impact can be achieved through retention of specific learned tasks as well as by strong external cues (daily pre-programmed ring), and can increase the quality of life for patients with DAT. PMID:19473956

  3. Quantifying Early Aftershock Activity of the 2004 Mid Niigata Prefecture Earthquake (Mw6.6)

    NASA Astrophysics Data System (ADS)

    Enescu, B.; Mori, J.; Miyazawa, M.

    2006-12-01

    We analyse the early aftershock activity of the 2004 Mid Niigata earthquake, using both earthquake catalog data and continuous waveform recordings. The frequency-magnitude distribution analysis of the Japan Meteorological Agency (JMA) catalog shows that the magnitude of completeness of the aftershocks changes from values around 5.0, immediately after the mainshock, to about 1.8, twelve hours later. Such a large incompleteness of early events can bias significantly the estimation of aftershock rates. To better determine the temporal pattern of aftershocks in the first minutes after the Niigata earthquake, we analyse the continuous seismograms recorded at six Hi-Net (High Sensitivity Seismograph Network) stations located close to the aftershock distribution. Clear aftershocks can be seen from about 35 sec. after the mainshock. We use events which are both identified on the filtered waveforms and are listed in the JMA catalogue, to calibrate an amplitude-magnitude relation. We estimate that the events picked on the waveforms recorded at two seismic stations (NGOH and YNTH), situated on opposite sides of the aftershock distribution, are complete above a threshold magnitude of 3.4. The c-value determined by taking these events into account is about 0.003 days (4.3 min). Statistical tests demonstrate that a small, but non-zero, c-value is a reliable result. We also analyse the decay with time of the moment release rates of the aftershocks in the JMA catalog, since these rates should be much less influenced by the missing small events. The moment rates follow a power-law time dependence from a few minutes to months after the mainshock. We finally show that the rate-and-state dependent friction law or stress corrosion could explain well our findings.

  4. 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

  5. Early growth response protein 1 acts as an activator of SOX18 promoter

    PubMed Central

    Petrovic, Isidora; Kovacevic-Grujicic, Natasa

    2010-01-01

    Sex-determining region Y box 18 (Sox18/SOX18) gene is an important regulator of vascular development playing a role in endothelial cell specification or differentiation, angiogenesis and atherogenesis. The aim of this study was to perform comprehensive functional characterization of the human SOX18 promoter, including determination of transcription start point (tsp) and identification of control elements involved in the regulation of SOX18 gene expression, with an emphasis on angiogenesis-related transcription factors. Analyses were performed in HeLa cells, representing a tumor cell line, and in EA.hy926 cells used as an endothelial model system. We have determined unique tsp of SOX18 gene, located 172 nucleotides upstream from ATG codon. Further, we have shown that SOX18 promoter region, -726 to -89 bp relative to tsp, contains positive cis-regulatory element(s) that stimulates SOX18 promoter activity, while region -89 to + 166 represents the minimal promoter. Within this region we have recognized the presence of essential element(s), positioned from -89 to +29, which harbors cluster of three putative early growth response 1 (EGR1) binding sites. By in vitro binding assays and functional analyses we have shown that these three putative binding sites are functionally relevant and sufficient for EGR1-induced SOX18 transcription. Mutations of these binding sites significantly impaired activity of the SOX18 promoter, particularly in EA.hy926 cells, indicating the importance of these regulatory elements for SOX18 promoter activity in endothelial setting. By data presented in this study, we have established SOX18 as a novel target gene regulated by EGR1 transcription factor, thus providing the first functional link between two transcription factors previously shown to be involved in the control of angiogenesis. PMID:20054233

  6. 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

  7. 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

  8. 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).

  9. The cost-utility of open prostatectomy compared with active surveillance in early localised prostate cancer

    PubMed Central

    2014-01-01

    Background There is an on-going debate about whether to perform surgery on early stage localised prostate cancer and risk the common long term side effects such as urinary incontinence and erectile dysfunction. Alternatively these patients could be closely monitored and treated only in case of disease progression (active surveillance). The aim of this paper is to develop a decision-analytic model comparing the cost-utility of active surveillance (AS) and radical prostatectomy (PE) for a cohort of 65 year old men with newly diagnosed low risk prostate cancer. Methods A Markov model comparing PE and AS over a lifetime horizon was programmed in TreeAge from a German societal perspective. Comparative disease specific mortality was obtained from the Scandinavian Prostate Cancer Group trial. Direct costs were identified via national treatment guidelines and expert interviews covering in-patient, out-patient, medication, aids and remedies as well as out of pocket payments. Utility values were used as factor weights for age specific quality of life values of the German population. Uncertainty was assessed deterministically and probabilistically. Results With quality adjustment, AS was the dominant strategy compared with initial treatment. In the base case, it was associated with an additional 0.04 quality adjusted life years (7.60 QALYs vs. 7.56 QALYs) and a cost reduction of €6,883 per patient (2011 prices). Considering only life-years gained, PE was more effective with an incremental cost-effectiveness ratio of €96,420/life year gained. Sensitivity analysis showed that the probability of developing metastases under AS and utility weights under AS are a major sources of uncertainty. A Monte Carlo simulation revealed that AS was more likely to be cost-effective even under very high willingness to pay thresholds. Conclusion AS is likely to be a cost-saving treatment strategy for some patients with early stage localised prostate cancer. However, cost-effectiveness is

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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

  17. Ability in daily activities after early supported discharge models of stroke rehabilitation

    PubMed Central

    Taule, Tina; Strand, Liv Inger; Assmus, Jörg; Skouen, Jan Sture

    2015-01-01

    Abstract More knowledge is needed about how different rehabilitation models in the municipality influence stroke survivors’ ability in activities of daily living (ADL). Objectives: To compare three models of outpatient rehabilitation; early supported discharge (ESD) in a day unit, ESD at home and traditional treatment in the municipality (control group), regarding change in ADL ability during the first three months after stroke. Methods: A group comparison study was designed within a randomized controlled trial. Included participants were tested with the Assessment of Motor and Process Skills (AMPS) at baseline and discharged directly home. Primary and secondary outcomes were the AMPS and the modified Rankin Scale (mRS). Results and conclusions: Included were 154 participants (57% men, median age 73 years), and 103 participants completed the study. There were no significant group differences in pre–post changed ADL ability measured by the AMPS. To find the best rehabilitation model to improve the quality of stroke survivors’ motor and process skills needs further research. Patients participating in the ESD rehabilitation models were, compared with traditional treatment, significantly associated with improved ADL ability measured by the mRS when controlling for confounding factors, indicating that patients with social needs and physical impairment after stroke may benefit from ESD rehabilitation models. PMID:26005768

  18. 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

  19. Carvedilol Analogue Inhibits Triggered Activities Evoked by Both Early and Delayed Afterdepolarizations

    PubMed Central

    Maruyama, Mitsunori; Xiao, Jianmin; Zhou, Qiang; Vembaiyan, Kannan; Chua, Su-Kiat; Rubart-von der Lohe, Michael; Lin, Shien-Fong; Back, Thomas G.; Chen, SR Wayne; Chen, Peng-Sheng

    2012-01-01

    BACKGROUND Carvedilol and its analogues suppress delayed afterdepolarizations (DADs) and catecholaminergic polymorphic ventricular tachycardias by direct action on the cardiac ryanodine receptor (RyR2). OBJECTIVE We tested a hypothesis that carvedilol analogue may also prevent triggered activities (TAs) through the suppression of early afterdepolarizations (EADs). METHODS Intracellular Ca2+ and membrane voltage were simultaneously recorded using optical mapping technique in Langendorff-perfused mouse and rabbit hearts to study the effect of carvedilol analogue, VK-II-36 that does not have significant beta-blocking effects. RESULTS Spontaneous intracellular Ca2+ elevations (SCaEs) during diastole was induced by rapid ventricular pacing and isoproterenol infusion in intact rabbit ventricles. Systolic and diastolic SCaEs were simultaneously noted in Langendorff-perfused RyR2 R4496+/− mouse hearts after creating atrioventricular block. VK-II-36 effectively suppressed SCaEs and eliminated TAs observed in both mouse and rabbit ventricles. We tested the effect of VK-II-36 on EADs using a rabbit model of acquired long QT syndrome in which phase-2 and phase-3 EADs were observed in association with systolic SCaEs. VK-II-36 abolished the systolic SCaEs and phase-2 EADs, and greatly decreased the dispersion of repolarization and the amplitude of phase-3 EADs. VK-II-36 completely prevented EAD-mediated TAs in all ventricles studied. CONCLUSION A carvedilol analogue, VK-II-36 inhibits ventricular tachyarrhythmias in intact mouse and rabbit ventricles by suppression of SCaEs, independent of beta-blocking activity. The RyR2 may be a potential target for treating focal ventricular arrhythmias triggered by either EADs or DADs. PMID:22982970

  20. Higher Activity of the Inducible Nitric Oxide Synthase Contributes to Very Early Onset Inflammatory Bowel Disease

    PubMed Central

    Dhillon, Sandeep S; Mastropaolo, Lucas A; Murchie, Ryan; Griffiths, Christopher; Thöni, Cornelia; Elkadri, Abdul; Xu, Wei; Mack, Amanda; Walters, Thomas; Guo, Conghui; Mack, David; Huynh, Hien; Baksh, Shairaz; Silverberg, Mark S; Brumell, John H; Snapper, Scott B; Muise, Aleixo M

    2014-01-01

    OBJECTIVES: The NOS2 gene encodes for the inducible nitric oxide synthase (iNOS), responsible for nitric oxide (NO) production, which contributes to antimicrobial and antipathogenic activities. Higher levels of both iNOS and NO-induced damage have been observed in inflammatory bowel disease (IBD) patients. NOS2 may have a role in a specific subset of IBD patients with severe and/or extensive colitis. Therefore, the aim of this study is to examine the role of NOS2 in such a subset, very early onset IBD (VEO-IBD). METHODS: Seventeen tag single nucleotide polymorphisms (SNPs) in the NOS2 gene were successfully genotyped in VEO-IBD patients. Genetic associations were replicated in an independent VEO-IBD cohort. Functional analysis for iNOS activity was performed on the most significantly associated functional variant. RESULTS: The NOS2 rs2297518 SNP was found to be associated in VEO-IBD in two independent cohorts. Upon combined analysis, a coding variant (S608L) showed the strongest association with VEO-IBD (Pcombined=1.13 × 10−6, OR (odds ratio)=3.398 (95% CI (confidence interval) 2.02–5.717)) as well as associations with VEO-Crohn's disease and VEO-ulcerative colitis (UC). This variant also showed an association with UC diagnosed between 11 and 17 years of age but not with adult-onset IBD (>17 years). B-cell lymphoblastoid cell lines genotyped for the risk variant as well as Henle-407 cells transfected with a plasmid construct with the risk variant showed higher NO production. Colonic biopsies of VEO-IBD patients showed higher immunohistochemical staining of nitrotyrosine, indicating more nitrosative stress and tissue damage. CONCLUSIONS: These studies suggest the importance of iNOS in genetic susceptibility to younger IBD presentation due to higher NO production. PMID:24430113

  1. Classical and Alternative Activation and Metalloproteinase Expression Occurs in Foam Cell Macrophages in Male and Female ApoE Null Mice in the Absence of T and B Lymphocytes

    PubMed Central

    Hayes, Elaine Mo; Tsaousi, Aikaterini; Di Gregoli, Karina; Jenkinson, S. Rhiannon; Bond, Andrew R.; Johnson, Jason L.; Bevan, Laura; Thomas, Anita C.; Newby, Andrew C.

    2014-01-01

    Background: Rupture of advanced atherosclerotic plaques accounts for most life-threatening myocardial infarctions. Classical (M1) and alternative (M2) macrophage activation could promote atherosclerotic plaque progression and rupture by increasing production of proteases, including matrix metalloproteinases (MMPs). Lymphocyte-derived cytokines may be essential for generating M1 and M2 phenotypes in plaques, although this has not been rigorously tested until now. Methods and results: We validated the expression of M1 markers (iNOS and COX-2) and M2 markers (arginase-1, Ym-1, and CD206) and then measured MMP mRNA levels in mouse macrophages during classical and alternative activation in vitro. We then compared mRNA expression of these genes ex vivo in foam cells from subcutaneous granulomas in fat-fed immune-competent ApoE knockout (KO) and immune-compromised ApoE/Rag-1 double-KO mice, which lack all T and B cells. Furthermore, we performed immunohistochemistry in subcutaneous granulomas and in aortic root and brachiocephalic artery atherosclerotic plaques to measure the extent of M1/M2 marker and MMP protein expression in vivo. Classical activation of mouse macrophages with bacterial lipopolysaccharide in vitro increased MMPs-13, -14, and -25 but decreased MMP-19 and TIMP-2 mRNA expressions. Alternative activation with IL-4 increased MMP-19 expression. Foam cells in subcutaneous granulomas expressed all M1/M2 markers and MMPs at ex vivo mRNA and in vivo protein levels, irrespective of Rag-1 genotype. There were also similar percentages of foam cell macrophages (FCMs) carrying M1/M2 markers and MMPs in atherosclerotic plaques from ApoE KO and ApoE/Rag-1 double-KO mice. Conclusion: Classical and alternative activation leads to distinct MMP expression patterns in mouse macrophages in vitro. M1 and M2 polarization in vivo occurs in the absence of T and B lymphocytes in either granuloma or plaque FCMs. PMID:25389425

  2. 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

  3. Targeting S1P receptors in experimental autoimmune encephalomyelitis in mice improves early deficits in locomotor activity and increases ultrasonic vocalisations.

    PubMed

    Sheridan, Graham K; Dev, Kumlesh K

    2014-01-01

    Fingolimod (FTY720) is an oral therapy for relapsing remitting multiple sclerosis (MS) and targets sphingosine 1-phosphate receptors (S1PRs). FTY720 also rescues animals from experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The protective effects of FTY720 in EAE are primarily scored manually by examining weight loss and limb paralysis that begins around 10-12 days after immunisation. To our knowledge, pre-clinical effects of FTY720 on animal behaviour early in EAE have not been explored. Here, we developed an automated behaviour monitoring system to examine the early effects of FTY720 on subtle pre-symptomatic behaviour of mice induced with EAE. Our automated home-cage monitoring system (AHC-MS) enabled non-contact detection of movement and ultrasonic vocalisations (USVs) of mice induced with EAE, thus allowing detection of subtle changes in mouse behaviour before paralysis occurs. Mice receiving FTY720 emit longer USVs and display higher levels of motor activity than vehicle-treated EAE mice before clinical symptoms become apparent. Importantly, this study promotes the 3Rs ethics (replacement, reduction and refinement) in the EAE animal model and may also improve pre-screening of potentially novel MS therapies. In addition, this is the first report showing the early effects of FTY720 in EAE which underscores its protective effects. PMID:24851861

  4. Lower Pre-Treatment T Cell Activation in Early- and Late-Onset Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome

    PubMed Central

    Goovaerts, Odin; Jennes, Wim; Massinga-Loembé, Marguerite; Ondoa, Pascale; Ceulemans, Ann; Vereecken, Chris; Worodria, William; Mayanja-Kizza, Harriet; Colebunders, Robert; Kestens, Luc

    2015-01-01

    Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an inflammatory complication in HIV-TB co-infected patients receiving antiretroviral therapy (ART). The role of disturbed T cell reconstitution in TB-IRIS is not well understood. We investigated T cell activation and maturation profiles in patients who developed TB-IRIS at different intervals during ART. Methods Twenty-two HIV-TB patients who developed early-onset TB-IRIS and 10 who developed late-onset TB-IRIS were matched for age, sex and CD4 count to equal numbers of HIV-TB patients who did not develop TB-IRIS. Flow cytometry analysis was performed on fresh blood, drawn before and after ART initiation and during TB-IRIS events. T cell activation and maturation was measured on CD4+ and CD8+ T cells using CD45RO, CD38, HLA-DR, CCR7 and CD27 antibodies. Results CD8+ T cell activation before ART was decreased in both early-onset (77% vs. 82%, p = 0.014) and late-onset (71% vs. 83%, p = 0.012) TB-IRIS patients compared to non-IRIS controls. After ART initiation, the observed differences in T cell activation disappeared. During late-onset, but not early-onset TB-IRIS, we observed a skewing from memory to terminal effector CD4+ and CD8+ T cell populations (p≤0.028). Conclusion Our data provide evidence of reduced CD8+ T cell activation before ART as a common predisposing factor of early- and late-onset TB-IRIS. The occurrence of TB-IRIS itself was not marked by an over-activated CD8+ T cell compartment. Late- but not early-onset TB-IRIS was characterized by a more terminally differentiated T cell phenotype. PMID:26208109

  5. Medication persistence over 2 years of follow-up in a cohort of early rheumatoid arthritis patients: associated factors and relationship with disease activity and with disability

    PubMed Central

    Pascual-Ramos, Virginia; Contreras-Yáñez, Irazú; Villa, Antonio R; Cabiedes, Javier; Rull-Gabayet, Marina

    2009-01-01

    Introduction Aggressive treatment with disease-modifying antirheumatic drugs (DMARDs) plays a major role in improving early rheumatoid arthritis (RA) patient outcomes. Persistence and adherence with medication occurs variably (20% to 70%). The objectives of the study were to determine medication persistence (MP) in early RA patients over 13 consecutive visits each 2 months apart, to investigate the relationship between MP and disease activity, disability and structural damage, and to identify baseline prognosticators. Methods Charts from 75 patients of an early RA cohort were reviewed. At each visit, a rheumatologist interviewed patients regarding therapy, scored disease activity with the 28-joint disease activity score (DAS28) and disability with the health assessment questionnaire (HAQ), and recorded comorbidities and treatment. A complete medical history was obtained at baseline. MP was defined as the duration of time from initiation to discontinuation of at least one DMARD and/or corticosteroids for at least 1 week and was reported as a dichotomous variable at consecutive evaluations. Structural damage was defined by detection of new erosions on radiography. Descriptive statistics, Student's t test, the chi-squared test, and logistic regression analyses were used. Results The proportion of MP patients decreased from 98% at 2 months to 34% at 2 years. MP patients (n = 32) had similar DAS28 to non-MP patients (n = 53) at initial visits, lower DAS28 and greater DAS28 improvements at follow-ups (P ≤ 0.05 at visits 4, 6, 7 and 9) and reached sustained remission (≥ 3 consecutive visits with DAS28 < 2.6) more frequently (82.8% versus 46.5%, P = 0.003) and earlier (7.7 ± 4.6 versus 13.6 ± 5.7 months, P = 0.001) than non-MP patients. MP patients had similar baseline HAQ scores, but lower HAQ scores at follow-up (P ≤ 0.05 at visits 3, 5, 6, 7, 9, 10 and 13). More non-MP patients developed erosive disease than MP patients (26.8% versus 17.9%, P = 0.56). Older age

  6. Enhancing Recognition of High Quality, Functional IEP Goals: A Training Activity for Early Childhood Special Education Staff

    ERIC Educational Resources Information Center

    Lucas, Anne; Gillaspy, Kathi; Peters, Mary Louise; Hurth, Joicey

    2014-01-01

    This training activity was created to support participants' understanding of the criteria needed to develop and write high quality, participation-based Individualized Education Program (IEP) goals. The term "functional" is often used to describe what goals ought to be, yet many Early Childhood Special Education (ECSE) staff (e.g.,…

  7. 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…

  8. 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.

  9. Parents' Perspectives of Early Childhood Special Education, Engagement in Everyday Learning Activities, and Kindergarten Performance of Children with Disabilities

    ERIC Educational Resources Information Center

    Epley, Pamela H.

    2013-01-01

    This study examined the relationship between parents' perspectives of early childhood special education (ECSE) and their engagement in everyday learning activities with kindergarten performance of children with disabilities in one Midwestern state. Findings show that although parents' perspective of ECSE and their engagement in everyday learning…

  10. 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…

  11. 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…

  12. 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.…

  13. Early Intervention Supports & Services in Everyday Routines, Activities, and Places in Colorado: A Guidebook.

    ERIC Educational Resources Information Center

    Edelman, Larry, Ed.

    The Program for Infants and Toddlers with Disabilities (Part C of IDEA, the Individuals with Disabilities Act) is a federal program that assists states in operating a system of early intervention supports and services for infants and toddlers with special needs and their families. In Colorado, the Part C initiative is called Early Childhood…

  14. 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

  15. Early Earth Science Activities in the Sanford Underground Science and Engineering Laboratory at Homestake

    NASA Astrophysics Data System (ADS)

    Wang, J. S.; Glaser, S. D.; Moore, J. R.; Hart, K.; King, G.; Regan, T.; Bang, S. S.; Sani, R. K.; Roggenthen, W. M.

    2007-12-01

    On July 10, 2007, the former Homestake Mine, Lead, South Dakota, was selected as the development site for the Deep Underground Science and Engineering Laboratory, to become the Sanford Underground Science and Engineering Laboratory at Homestake. Work on refurbishment and certification of the Ross Shaft began in August 2007 to effect pumping of water that had reached the 5000 level in late July. Completion of this work will allow a physics and geosciences laboratory to be constructed on the 4,850 ft level (1,478 m from the surface). Concurrent with reentry operations, several earth science research activities have been initiated. These early activities are as follows: (1) Seismic monitoring system: Accelerometers will be installed in surface boreholes and underground drifts as they become available as a result of the reentry work. (2) Evaluation of the 300 level (91 m), which has multiple locations for horizontal access, is ongoing. This near- surface level, with varying overburden thicknesses, offers excellent opportunities to investigate the "critical zone" in terms of hydrology, ecology, and geochemistry, yielding measurements of both moisture and carbon fluxes to evaluate fluid exchanges with the atmosphere. (3) Water and soil samples were collected in the Ross Shaft as part of the first reentry work. Molecular survey of microbial diversity showed the presence of mesophilic and thermophilic cellulose-degrading microorganisms. (4) Supercritical carbon dioxide injection experiments are being planned that will take advantage of three pairs of existing, nearly vertical, open 8-inch (0.2 m) boreholes that are easily accessible from the Ross Shaft. The candidate holes are located between the 1550 and the 2900 levels and are between 90 to 180 m in length (5) Monitoring of the response of the water during the dewatering operations will be facilitated by the use of existing boreholes. Ultimately, the dewatering operation provide access to the 8000 level (depth of 2,438 m

  16. Downregulation of protein kinase PKR activation by porcine reproductive and respiratory syndrome virus at its early stage infection.

    PubMed

    Xiao, Yueqiang; Ma, Zexu; Wang, Rong; Yang, Liping; Nan, Yuchen; Zhang, Yan-Jin

    2016-05-01

    The interferon-induced double-strand RNA activated protein kinase (PKR) plays an important role in antiviral response. The objective of this study was to assess the effect of porcine reproductive and respiratory syndrome virus (PRRSV) on PKR activation. Here we report that PRRSV inhibited PKR activation during its early stage infection of primary pulmonary alveolar macrophages (PAMs). PRRSV infection led to lower level of phosphorylated PKR in comparison with mock-infected cells. The PKR inhibition was sustained until 10h post infection in the presence of polyI:C, a synthetic analog of double-stranded RNA activating PKR. PKR-mediated phosphorylation of the eukaryotic translation initiation factor eIF2α was also lower in the PRRSV-infected PAMs during the early stage infection. Interestingly, inactivated PRRSV was capable to inhibit the PKR activation until 6h post infection. This suggests that structural components of PRRSV virions were responsible for the inhibition, although PRRSV replication was needed for longer inhibition. These results indicate that the downregulation of PKR activation during early infection stage should be essential for PRRSV to avoid the antiviral response to initiate replication. This finding contributes to our understanding on PRRSV interaction with host innate immune response and reveal a target for control of PRRSV infection. PMID:27066702

  17. 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.

  18. Early functional magnetic resonance imaging activations predict language outcome after stroke.

    PubMed

    Saur, Dorothee; Ronneberger, Olaf; Kümmerer, Dorothee; Mader, Irina; Weiller, Cornelius; Klöppel, Stefan

    2010-04-01

    An accurate prediction of system-specific recovery after stroke is essential to provide rehabilitation therapy based on the individual needs. We explored the usefulness of functional magnetic resonance imaging scans from an auditory language comprehension experiment to predict individual language recovery in 21 aphasic stroke patients. Subjects with an at least moderate language impairment received extensive language testing 2 weeks and 6 months after left-hemispheric stroke. A multivariate machine learning technique was used to predict language outcome 6 months after stroke. In addition, we aimed to predict the degree of language improvement over 6 months. 76% of patients were correctly separated into those with good and bad language performance 6 months after stroke when based on functional magnetic resonance imaging data from language relevant areas. Accuracy further improved (86% correct assignments) when age and language score were entered alongside functional magnetic resonance imaging data into the fully automatic classifier. A similar accuracy was reached when predicting the degree of language improvement based on imaging, age and language performance. No prediction better than chance level was achieved when exploring the usefulness of diffusion weighted imaging as well as functional magnetic resonance imaging acquired two days after stroke. This study demonstrates the high potential of current machine learning techniques to predict system-specific clinical outcome even for a disease as heterogeneous as stroke. Best prediction of language recovery is achieved when the brain activation potential after system-specific stimulation is assessed in the second week post stroke. More intensive early rehabilitation could be provided for those with a predicted poor recovery and the extension to other systems, for example, motor and attention seems feasible. PMID:20299389

  19. Glycolytic-to-oxidative fiber-type switch and mTOR signaling activation are early-onset features of SBMA muscle modified by high-fat diet.

    PubMed

    Rocchi, Anna; Milioto, Carmelo; Parodi, Sara; Armirotti, Andrea; Borgia, Doriana; Pellegrini, Matteo; Urciuolo, Anna; Molon, Sibilla; Morbidoni, Valeria; Marabita, Manuela; Romanello, Vanina; Gatto, Pamela; Blaauw, Bert; Bonaldo, Paolo; Sambataro, Fabio; Robins, Diane M; Lieberman, Andrew P; Sorarù, Gianni; Vergani, Lodovica; Sandri, Marco; Pennuto, Maria

    2016-07-01

    Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by the expansion of a polyglutamine tract in the androgen receptor (AR). The mechanism by which expansion of polyglutamine in AR causes muscle atrophy is unknown. Here, we investigated pathological pathways underlying muscle atrophy in SBMA knock-in mice and patients. We show that glycolytic muscles were more severely affected than oxidative muscles in SBMA knock-in mice. Muscle atrophy was associated with early-onset, progressive glycolytic-to-oxidative fiber-type switch. Whole genome microarray and untargeted lipidomic analyses revealed enhanced lipid metabolism and impaired glycolysis selectively in muscle. These metabolic changes occurred before denervation and were associated with a concurrent enhancement of mechanistic target of rapamycin (mTOR) signaling, which induced peroxisome proliferator-activated receptor γ coactivator 1 alpha (PGC1α) expression. At later stages of disease, we detected mitochondrial membrane depolarization, enhanced transcription factor EB (TFEB) expression and autophagy, and mTOR-induced protein synthesis. Several of these abnormalities were detected in the muscle of SBMA patients. Feeding knock-in mice a high-fat diet (HFD) restored mTOR activation, decreased the expression of PGC1α, TFEB, and genes involved in oxidative metabolism, reduced mitochondrial abnormalities, ameliorated muscle pathology, and extended survival. These findings show early-onset and intrinsic metabolic alterations in SBMA muscle and link lipid/glucose metabolism to pathogenesis. Moreover, our results highlight an HFD regime as a promising approach to support SBMA patients. PMID:26971100

  20. Naturally Occuring Fish Poisons from Plants

    NASA Astrophysics Data System (ADS)

    Cannon, Jonathan G.; Burton, Robert A.; Wood, Steven G.; Owen, Noel L.

    2004-10-01

    Since prehistoric times, cultures throughout the world have used piscicidal (fish poisoning) plants for fishing. In recent times, scientists have identified many of the plant compounds responsible for killing the fish and have found that these compounds possess other important biological properties, such as insecticidal and anti-cancer activities. This article reviews some of the chemical research that has been performed on naturally occurring fish poisons, including plant sources, methods of use, toxicity, and mechanisms of action of piscicides.

  1. Effect of major burns on early and late activating markers of peripheral blood T lymphocytes.

    PubMed

    Sayed, S; Bakry, R; El-Shazly, M; El-Oteify, M; Terzaki, S; Fekry, M

    2012-03-31

    It is known that lymphocytes immunophenotype is a reflection of the functional level of the immune system. The immunosuppressive effect of major burns is also known for many years. T lymphocytes of 50 major burn patients were analyzed in base line (BL) samples at 24 hours and at 1 week and 2 weeks after burn, using monoclonal antibodies of CD3, CD4, CD8, CD25 (IL2R) and HLA-DR by flow cytometry and β2-microglobulin (β2-m) by ELISA. Recorded values were compared with those of 50 healthy donors. There was statistically significant reduction in absolute number of CD3 positive cells (CD3+) (p<0.000) and CD4/CD8 ratio (p=0.01) in the first 24 hours in comparison with controls. CD25 (IL-2R) shows insignificant upregulation on T lymphocytes after burn with significant upregulation of HLA-DR. The absolute number of CD3+ cells began to increase after 2 weeks (p=0.03) but remained less than controls (p=0.08). CD4/CD8 ratio was more or less same as healthy controls after 2 weeks. Upregulation of CD25 was insignificantly increased and that of HLA-DR was markedly increased after 2 weeks (p=0.001). Significant negative correlations were detected between mean values of β2-m and both absolute numbers of CD3 and CD4 positive cells in BL and one week samples. In addition there was significant correlation between mean values of β2-m and values of CD25 expression in the BL samples. The obtained data is suggestive of persistent activation of T lymphocytes two weeks after major burns whereas early shedding of β2-m is related to activation of lymphocytes increasing their susceptibility to apoptosis, both indicative of altered immune response. Burn intensivists and surgeons should be keen to support the patients' immune system in the first hours following major burns. This support will ensure free-bacteremic blood with a consequent better prognosis. PMID:23012611

  2. Fish-Free Diet in Patients with Phenylketonuria Is Not Associated with Early Atherosclerotic Changes and Enhanced Platelet Activation

    PubMed Central

    Htun, Patrik; Nee, Jens; Ploeckinger, Ursula; Eder, Klaus; Geisler, Tobias; Gawaz, Meinrad; Bocksch, Wolfgang; Fateh-Moghadam, Suzanne

    2015-01-01

    Background and Purpose Since patients with phenylketonuria (PKU) have to follow a lifelong restriction of natural protein to lower phenylalanine-intake, they never eat fish. This diet may lead to a chronic deficit of omega-3 and omega-6 fatty acids with the risk of early atherosclerotic changes. The aim of the study was to analyse the fatty acid profile of PKU patients and to correlate the results with surrogate markers of early atherosclerotic changes [enhanced carotid intima media thickness (CIMT) and ß-stiffness index] and platelet activation. Methods In 43 PKU patients and in 58 healthy controls we prospectively examined the fatty acid profile, CIMT, ß-stiffness index and platelet activation (flow cytometric determination of markers of platelet activation). CIMT was measured bilaterally by ultrasound. CIMT mean was defined as the mean value of the sum of CIMT left and CIMT right. Results Despite of lower HDL-cholesterol and higher triglyceride concentrations in the PKU group, there was no significant difference in the omega-6 or omega-3 fatty acid profile, CIMT, ß-stiffness index between both groups. Platelet activation was not enhanced in the PKU group. Conclusions Fish-free diet does not induce early atherosclerotic changes or enhanced platelet ac