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Sample records for a20 regulates period

  1. Environmental Volunteering and Health Outcomes over a 20-Year Period

    ERIC Educational Resources Information Center

    Pillemer, Karl; Fuller-Rowell, Thomas E.; Reid, M. C.; Wells, Nancy M.

    2010-01-01

    Purpose: This study tested the hypothesis that volunteering in environmental organizations in midlife is associated with greater physical activity and improved mental and physical health over a 20-year period. Design and Methods: The study used data from two waves (1974 and 1994) of the Alameda County Study, a longitudinal study of health and…

  2. Environmental Volunteering and Health Outcomes over a 20-Year Period

    ERIC Educational Resources Information Center

    Pillemer, Karl; Fuller-Rowell, Thomas E.; Reid, M. C.; Wells, Nancy M.

    2010-01-01

    Purpose: This study tested the hypothesis that volunteering in environmental organizations in midlife is associated with greater physical activity and improved mental and physical health over a 20-year period. Design and Methods: The study used data from two waves (1974 and 1994) of the Alameda County Study, a longitudinal study of health and…

  3. Environmental Volunteering and Health Outcomes over a 20-Year Period

    PubMed Central

    Pillemer, Karl; Fuller-Rowell, Thomas E.; Reid, M. C.; Wells, Nancy M.

    2010-01-01

    Purpose: This study tested the hypothesis that volunteering in environmental organizations in midlife is associated with greater physical activity and improved mental and physical health over a 20-year period.  Design and Methods: The study used data from two waves (1974 and 1994) of the Alameda County Study, a longitudinal study of health and mortality that has followed a cohort of 6,928 adults since 1965. Using logistic and multiple regression models, we examined the prospective association between environmental and other volunteerism and three outcomes (physical activity, self-reported health, and depression), with 1974 volunteerism predicting 1994 outcomes, controlling for a number of relevant covariates.  Results: Midlife environmental volunteering was significantly associated with physical activity, self-reported health, and depressive symptoms.  Implications: This population-based study offers the first epidemiological evidence for a significant positive relationship between environmental volunteering and health and well-being outcomes. Further research, including intervention studies, is needed to confirm and shed additional light on these initial findings. PMID:20172902

  4. A20 Ameliorates Intracerebral Hemorrhage–Induced Inflammatory Injury by Regulating TRAF6 Polyubiquitination

    PubMed Central

    Meng, Zhaoyou; Zhao, Ting; Zhou, Kai; Zhong, Qi; Wang, Yanchun; Xiong, Xiaoyi; Wang, Faxiang; Yang, Yuanrui; Zhu, Wenyao; Liu, Juan; Liao, Maofan; Wu, Lirong; Duan, Chunmei; Li, Jie; Gong, Qiuwen; Liu, Liang; Xiong, Ao; Yang, Meihua; Wang, Jian

    2017-01-01

    Reducing excessive inflammation is beneficial for the recovery from intracerebral hemorrhage (ICH). Here, the roles and mechanisms of A20 (TNFAIP3), an important endogenous anti-inflammatory factor, are examined in ICH. A20 expression in the PBMCs of ICH patients and an ICH mouse model was detected, and the correlation between A20 expression and neurologic deficits was analyzed. A20 expression was increased in PBMCs and was negatively related to the modified Rankin Scale score. A20 expression was also increased in mouse perihematomal tissues. A20−/− and A20-overexpressing mice were generated to further analyze A20 function. Compared with wild-type (WT) mice, A20−/− and A20-overexpressing mice showed significant increases and decreases, respectively, in hematoma volume, neurologic deficit score, mortality, neuronal degeneration, and proinflammatory factors. Moreover, WT-A20−/− parabiosis was established to explore the role of A20 in peripheral blood in ICH injury. ICH-induced damage, including brain edema, neurologic deficit score, proinflammatory factors, and neuronal apoptosis, was reduced in A20−/− parabionts compared with A20−/− mice. Finally, the interactions between TRAF6 and Ubc13 and UbcH5c were increased in A20−/− mice compared with WT mice; the opposite occurred in A20-overexpressing mice. Enhanced IκBα degradation and NF-κB activation were observed in A20−/− mice, but the results were reversed in A20-overexpressing mice. These results suggested that A20 is involved in regulating ICH-induced inflammatory injury in both the central and peripheral system and that A20 reduces ICH-induced inflammation by regulating TRAF6 polyubiquitination. Targeting A20 may thus be a promising therapeutic strategy for ICH. PMID:27986908

  5. [TRENDS OF PERMANENT PACEMAKER IMPLANTATION IN A SINGLE CENTER OVER A 20-YEAR PERIOD].

    PubMed

    Antonelli, Dante; Ilan, Limor Bushar; Freedberg, Nahum A; Feldman, Alexander; Turgeman, Yoav

    2015-05-01

    To review the changes in permanent pacemaker implantation indications, pacing modes and patients' demographics over a 20-year period. We retrospectively retrieved data on patients who underwent first implantation of the pacemaker between 1-1-1991 and 31-12-2010. One thousand and nine (1,009) patients underwent a first pacemaker implantation during that period; 535 were men (53%), their mean age was 74.6±19.5 years; the highest rate of implanted pacemaker was in patients ranging in age from 70-79 years, however there was an increasing number of patients aged over 80 years. The median survival time after initial pacemaker implantation was 8 years. Syncope was the most common symptom (62.5%) and atrioventricular block was the most common electrocardiographic indication (56.4%) leading to pacemaker implantation. There was increased utilization of dual chamber and rate responsive pacemakers over the years. There was no difference regarding mode selection between genders. Pacemaker implantation rates have increased over a 20-year period. Dual chamber replaced most of the single ventricular chamber pacemaker and rate responsive pacemakers became the norm. The data of a small volume center are similar to those reported in pacemaker surveys of high volume pacemaker implantation centers. They confirm adherence to the published guidelines for pacing.

  6. A20: linking a complex regulator of ubiquitylation to immunity and human disease

    PubMed Central

    Ma, Averil; Malynn, Barbara A.

    2013-01-01

    A20 (also known as TNFAIP3) is a potent anti-inflammatory signalling molecule that restricts multiple intracellular signalling cascades. Recent studies in three general areas have converged to highlight the clinical and biological importance of A20. First, human genetic studies have strongly linked polymorphisms and mutations in the gene encoding A20 to inflammatory, autoimmune and malignant diseases. Second, studies in gene-targeted mice have revealed that A20 regulates multiple immune cell functions and prevents experimental diseases that closely mimic human conditions. Third, biochemical studies have unveiled complex mechanisms by which A20 regulates ubiquitin-dependent nuclear factor-κB and cell-survival signals. Taken together, these studies are revealing the importance of A20-mediated regulation of ubiquitin-dependent signalling in human disease. PMID:23059429

  7. Up-regulated A20 promotes proliferation, regulates cell cycle progression and induces chemotherapy resistance of acute lymphoblastic leukemia cells.

    PubMed

    Chen, Shuying; Xing, Haiyan; Li, Shouyun; Yu, Jing; Li, Huan; Liu, Shuang; Tian, Zheng; Tang, Kejing; Rao, Qing; Wang, Min; Wang, Jianxiang

    2015-09-01

    A20, also known as tumor necrosis factor-α (TNFα)-induced protein 3 (TNFAIP3), has been identified as a key regulator of cell survival in many solid tumors. However, little is known about the protein expression level and function of A20 in acute lymphoblastic leukemia (ALL). In this study, we found that A20 is up-regulated in ALL patients and several cell lines. Knockdown of A20 in Jurkat, Nalm-6, and Reh cells resulted in reduced cell proliferation, which was associated with cell cycle arrest. Phospho-ERK (p-ERK) was also down-regulated, while p53 and p21 were up-regulated in A20 knockdown cells. In addition, A20 knockdown induced apoptosis in Jurkat and Reh cells and enhanced the sensitivity of these cell lines to chemotherapeutic drugs. These results indicate that A20 may stimulate cell proliferation by regulating cell cycle progression. A20 inhibited apoptosis in some types of ALL cells, thereby enhancing their resistance to chemotherapy. This effect was abolished through A20 silencing. These findings suggest that A20 may contribute to the pathogenesis of ALL and that it may be used as a new therapeutic target for ALL treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Changes in plant species composition of coastal dune habitats over a 20-year period.

    PubMed

    Del Vecchio, Silvia; Prisco, Irene; Acosta, Alicia T R; Stanisci, Angela

    2015-03-05

    Coastal sandy ecosystems are increasingly being threatened by human pressure, causing loss of biodiversity, habitat degradation and landscape modifications. However, there are still very few detailed studies focussing on compositional changes in coastal dune plant communities over time. In this work, we investigated how coastal dune European Union (EU) habitats (from pioneer annual beach communities to Mediterranean scrubs on the landward fixed dunes) have changed during the last 20 years. Using phytosociological relevés conducted in 1989-90 and in 2010-12, we investigated changes in floristic composition over time. We then compared plant cover and the proportion of ruderal, alien and habitat diagnostic species ('focal species') in the two periods. Finally, we used Ellenberg indicator values to define the 'preferences' of the plant species for temperature and moisture. We found that only fore dune habitats showed significant differences in species cover between the two time periods, with higher plant cover in the more recent relevés and a significant increase in thermophilic species. Although previous studies have demonstrated consistent habitat loss in this area, we observed that all coastal dune plant communities remain well represented, after a 20-year period. However, fore dunes have been experiencing significant compositional changes. Although we cannot confirm whether the observed changes are strictly related to climatic changes, to human pressure or to both, we hypothesize that a moderate increment in average yearly temperature may have promoted the increase in plant cover and the spread of thermophilic species. Thus, even though human activities are major driving forces of change in coastal dune vegetation, at the community scale climatic factors may also play important roles. Our study draws on re-visitation studies which appear to constitute a powerful tool for the assessment of the conservation status of EU habitats.

  9. Changes in plant species composition of coastal dune habitats over a 20-year period

    PubMed Central

    Del Vecchio, Silvia; Prisco, Irene; Acosta, Alicia T. R.; Stanisci, Angela

    2015-01-01

    Coastal sandy ecosystems are increasingly being threatened by human pressure, causing loss of biodiversity, habitat degradation and landscape modifications. However, there are still very few detailed studies focussing on compositional changes in coastal dune plant communities over time. In this work, we investigated how coastal dune European Union (EU) habitats (from pioneer annual beach communities to Mediterranean scrubs on the landward fixed dunes) have changed during the last 20 years. Using phytosociological relevés conducted in 1989–90 and in 2010–12, we investigated changes in floristic composition over time. We then compared plant cover and the proportion of ruderal, alien and habitat diagnostic species (‘focal species’) in the two periods. Finally, we used Ellenberg indicator values to define the ‘preferences’ of the plant species for temperature and moisture. We found that only fore dune habitats showed significant differences in species cover between the two time periods, with higher plant cover in the more recent relevés and a significant increase in thermophilic species. Although previous studies have demonstrated consistent habitat loss in this area, we observed that all coastal dune plant communities remain well represented, after a 20-year period. However, fore dunes have been experiencing significant compositional changes. Although we cannot confirm whether the observed changes are strictly related to climatic changes, to human pressure or to both, we hypothesize that a moderate increment in average yearly temperature may have promoted the increase in plant cover and the spread of thermophilic species. Thus, even though human activities are major driving forces of change in coastal dune vegetation, at the community scale climatic factors may also play important roles. Our study draws on re-visitation studies which appear to constitute a powerful tool for the assessment of the conservation status of EU habitats. PMID:25750408

  10. Prenatal Diagnosis of Transposition of the Great Arteries over a 20-Year Period: Improved but Imperfect

    PubMed Central

    Escobar-Diaz, Maria C; Freud, Lindsay R; Bueno, Alejandra; Brown, David W; Friedman, Kevin; Schidlow, David; Emani, Sitaram; del Nido, Pedro; Tworetzky, Wayne

    2015-01-01

    Objective To evaluate temporal trends in prenatal diagnosis of transposition of the great arteries with intact ventricular septum (TGA/IVS) and its impact on neonatal morbidity and mortality. Methods Newborns with TGA/IVS referred for surgical management to our center over a 20-year period (1992 – 2011) were included. The study time was divided into 5 four-year periods, and the primary outcome was rate of prenatal diagnosis. Secondary outcomes included neonatal pre-operative status and perioperative survival. Results Of the 340 patients, 81 (24%) had a prenatal diagnosis. Prenatal diagnosis increased over the study period from 6% to 41% (p<0.001). Prenatally diagnosed patients underwent a balloon atrial septostomy (BAS) earlier than postnatally diagnosed patients (0 vs. 1 day, p<0.001) and fewer required mechanical ventilation (56% vs. 69%, p=0.03). There were no statistically significant differences in pre-operative acidosis (16% vs. 26%, p=0.1) and need for preoperative ECMO (2% vs. 3%, p=1.0). There was also no significant mortality difference (1 pre-operative and no post-operative deaths among prenatally diagnosed patients, as compared to 4 pre-operative and 6 post-operative deaths among postnatally diagnosed patients). Conclusion The prenatal detection rate of TGA/IVS has improved but still remains below 50%, suggesting the need for strategies to increase detection rates. The mortality rate was not statistically different between pre- and postnatally diagnosed patients; however, there were significant pre-operative differences with regard to earlier BAS and less mechanical ventilation. Ongoing study is required to elucidate whether prenatal diagnosis confers long-term benefit. PMID:25484180

  11. Prenatal diagnosis of transposition of the great arteries over a 20-year period: improved but imperfect.

    PubMed

    Escobar-Diaz, M C; Freud, L R; Bueno, A; Brown, D W; Friedman, K G; Schidlow, D; Emani, S; Del Nido, P J; Tworetzky, W

    2015-06-01

    To evaluate temporal trends in the prenatal diagnosis of transposition of the great arteries with intact ventricular septum (TGA/IVS) and its impact on neonatal morbidity and mortality. We included in this study cohort newborns with TGA/IVS who were referred for surgical management to our center over a 20-year period (1992-2011). The study period was divided into five 4-year periods and the primary outcome was rate of prenatal diagnosis. Secondary outcomes included neonatal preoperative status and perioperative survival. Of the 340 patients with TGA/IVS, 81 (23.8%) had a prenatal diagnosis. The rate of prenatal diagnosis increased over the study period, from 6% in 1992-1995 to 41% in 2008-2011 (P < 0.001). Compared to patients with a postnatal diagnosis, balloon atrial septostomy (BAS) was performed earlier in patients with a prenatal diagnosis (0 days after delivery vs 1 day after delivery, respectively; P < 0.001) and fewer prenatally diagnosed neonates required mechanical ventilation (55.6% vs 68.0%; P = 0.03). Between patients with a prenatal or postnatal diagnosis of TGA/IVS, there were no statistically significant differences in the incidence of preoperative acidosis (16.0% vs 25.5%; P = 0.1), need for preoperative extracorporeal membrane oxygenation (2.5% vs 2.7%; P = 1.0) or mortality (one preoperative and no postoperative deaths among prenatally diagnosed patients compared with four preoperative and six postoperative deaths among postnatally diagnosed patients). The prenatal detection rate of TGA/IVS has improved but still remains below 50%, suggesting the need for strategies to increase detection rates. The mortality rate was not statistically significantly different between prenatally and postnatally diagnosed patients, however, there were significant preoperative differences with regard to earlier BAS and fewer neonates that required mechanical ventilation. Ongoing work is required to ascertain whether prenatal diagnosis confers

  12. Socioeconomic factors and mortality in emergency general surgery: trends over a 20-year period.

    PubMed

    Armenia, Sarah J; Pentakota, Sri Ram; Merchant, Aziz M

    2017-05-15

    Socioeconomic factors such as race, insurance, and income quartiles have been identified as independent risk factors in emergency general surgery (EGS), but this impact has not been studied over time. We sought to identify trends in disparities in EGS-related operative mortality over a 20-y period. The National Inpatient Sample was used to identify patient encounters coded for EGS in 1993, 2003, and 2013. Logistic regression models were used to examine the adjusted relationship between race, primary payer status, and median income quartiles and in-hospital mortality after adjusting for patients' age, gender, Elixhauser comorbidity score, and hospital region, size, and location-cum-teaching status. We identified 391,040 patient encounters. In 1993, Black race was associated with higher odds of in-hospital mortality (odds ratio [95% confidence interval]: 1.35 [1.20-1.53]) than White race, although this difference dissipated in subsequent years. Medicare, Medicaid, and underinsured patients had a higher odds of mortality than those with private insurance for the entire 20-y period; only the disparity in the underinsured decreased over time (1993, 1.63 [1.35-1.98]; 2013, 1.41 [1.20-1.67]). In 2003 (1.23 [1.10-1.38]) and 2013 (1.23 [1.11-1.37]), patients from the lowest income quartile were more likely to die after EGS than patients from the highest income quartile. Socioeconomic disparities in EGS-related operative morality followed inconsistent trends. Over time, while gaps in in-hospital mortality among Blacks and Whites have narrowed, disparities among patients belonging to lowest income quartile have worsened. Medicare and Medicaid beneficiaries continued to experience higher odds of in-hospital mortality relative to those with private insurance. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Light period regulation of carbohydrate partitioning

    NASA Technical Reports Server (NTRS)

    Janes, Harry W.

    1994-01-01

    We have shown that the photosynthetic period is important in regulating carbon partitioning. Even when the same amount of carbon is fixed over a 24h period considerably more is translocated out of the leaf under the longer photosynthetic period. This is extremely important when parts of the plant other than the leaves are to be sold. It is also important to notice the amount of carbon respired in the short photosynthetic period. The light period effect on carbohydrate fixation, dark respiration, and translocation is shown in this report.

  14. Survival Trends After Surgery for Acute Subdural Hematoma in Adults Over a 20-year Period

    PubMed Central

    Fountain, Daniel M.; Kolias, Angelos G.; Lecky, Fiona E.; Bouamra, Omar; Lawrence, Thomas; Adams, Hadie; Bond, Simon J.; Hutchinson, Peter J.

    2017-01-01

    Objective: We sought to determine 30-day survival trends and prognostic factors following surgery for acute subdural hematomas (ASDHs) in England and Wales over a 20-year period. Summary of Background Data: ASDHs are still considered the most lethal type of traumatic brain injury. It remains unclear whether the adjusted odds of survival have improved significantly over time. Methods: Using the Trauma Audit and Research Network (TARN) database, we analyzed ASDH cases in the adult population (>16 yrs) treated surgically between 1994 and 2013. Two thousand four hundred ninety-eight eligible cases were identified. Univariable and multiple logistic regression analyses were performed, using multiple imputation for missing data. Results: The cohort was 74% male with a median age of 48.9 years. Over half of patients were comatose at presentation (53%). Mechanism of injury was due to a fall (<2 m 34%, >2 m 24%), road traffic collision (25%), and other (17%). Thirty-six per cent of patients presented with polytrauma. Gross survival increased from 59% in 1994 to 1998 to 73% in 2009 to 2013. Under multivariable analysis, variables independently associated with survival were year of injury, Glasgow Coma Scale, Injury Severity Score, age, and pupil reactivity. The time interval from injury to craniotomy and direct admission to a neurosurgical unit were not found to be significant prognostic factors. Conclusions: A significant improvement in survival over the last 20 years was observed after controlling for multiple prognostic factors. Prospective trials and cohort studies are expected to elucidate the distribution of functional outcome in survivors. PMID:27172128

  15. Induction of the inflammatory regulator A20 by gibberellic acid in airway epithelial cells.

    PubMed

    Reihill, J A; Malcomson, B; Bertelsen, A; Cheung, S; Czerwiec, A; Barsden, R; Elborn, J S; Dürkop, H; Hirsch, B; Ennis, M; Kelly, C; Schock, B C

    2016-02-01

    NF-κB-driven inflammation is negatively regulated by the zinc finger protein A20. Gibberellic acid (GA3 ) is a plant-derived diterpenoid with documented anti-inflammatory activity, which is reported to induce A20-like zinc finger proteins in plants. Here, we sought to investigate the anti-inflammatory effect of GA3 in airway epithelial cells and determine if the anti-inflammatory action relates to A20 induction. Primary nasal epithelial cells and a human bronchial epithelial cell line (16HBE14o-) were used. Cells were pre-incubated with GA3 , stimulated with Pseudomonas aeruginosa LPS; IL-6 and IL-8 release, A20, NF-κB and IκBα expression were then evaluated. To determine if any observed anti-inflammatory effect occurred via an A20-dependent mechanism, A20 was silenced using siRNA. Cells pre-incubated with GA3 had significantly increased levels of A20 mRNA (4 h) and protein (24 h), resulting in a significant reduction in IL-6 and IL-8 release. This effect was mediated via reduced IκBα degradation and reduced NF-κB (p65) expression. Furthermore, the anti-inflammatory action of GA3 was abolished in A20-silenced cells. We showed that A20 induction by GA3 attenuates inflammation in airway epithelial cells, at least in part through its effect on NF-κB and IκBα. GA3 or gibberellin-derived derivatives could potentially be developed into anti-inflammatory drugs for the treatment of chronic inflammatory diseases associated with A20 dysfunction. © 2015 The British Pharmacological Society.

  16. The Effect of a 20 km Run on Appetite Regulation in Long Distance Runners.

    PubMed

    Kojima, Chihiro; Ishibashi, Aya; Ebi, Kumiko; Goto, Kazushige

    2016-10-26

    The purpose of the present study was to investigate appetite-related hormonal responses and energy intake after a 20 km run in trained long distance runners. Twenty-three male long-distance runners completed two trials: either an exercise trial consisting of a 20 km outdoor run (EX) or a control trial with an identical period of rest (CON). Blood samples were collected to determine plasma acylated ghrelin, peptide YY3-36 (PYY3-36) and other hormonal and metabolite concentrations. Energy intake during a buffet test meal was also measured 30 min after the exercise or rest periods. Although plasma acylated ghrelin concentrations were significantly decreased after the 20 km run (p < 0.05), plasma PYY3-36 did not change significantly following exercise. Absolute energy intake during the buffet test meal in EX (1325 ± 55 kcal) was significantly lower than that in CON (1529 ± 55 kcal), and there was a relatively large degree of individual variability for exercise-induced changes in energy intake (-40.2% to 12.8%). However, exercise-induced changes in energy intake were not associated with plasma acylated ghrelin or PYY3-36 responses. The results demonstrated that a 20 km run significantly decreased plasma acylated ghrelin concentrations and absolute energy intake among well-trained long distance runners.

  17. The Effect of a 20 km Run on Appetite Regulation in Long Distance Runners

    PubMed Central

    Kojima, Chihiro; Ishibashi, Aya; Ebi, Kumiko; Goto, Kazushige

    2016-01-01

    The purpose of the present study was to investigate appetite-related hormonal responses and energy intake after a 20 km run in trained long distance runners. Twenty-three male long-distance runners completed two trials: either an exercise trial consisting of a 20 km outdoor run (EX) or a control trial with an identical period of rest (CON). Blood samples were collected to determine plasma acylated ghrelin, peptide YY3-36 (PYY3-36) and other hormonal and metabolite concentrations. Energy intake during a buffet test meal was also measured 30 min after the exercise or rest periods. Although plasma acylated ghrelin concentrations were significantly decreased after the 20 km run (p < 0.05), plasma PYY3-36 did not change significantly following exercise. Absolute energy intake during the buffet test meal in EX (1325 ± 55 kcal) was significantly lower than that in CON (1529 ± 55 kcal), and there was a relatively large degree of individual variability for exercise-induced changes in energy intake (−40.2% to 12.8%). However, exercise-induced changes in energy intake were not associated with plasma acylated ghrelin or PYY3-36 responses. The results demonstrated that a 20 km run significantly decreased plasma acylated ghrelin concentrations and absolute energy intake among well-trained long distance runners. PMID:27792164

  18. A20 regulates IL-1-induced tolerant production of CXC chemokines in human mesangial cells via inhibition of MAPK signaling

    PubMed Central

    Luo, Hongbo; Liu, Yuming; Li, Qian; Liao, Lingjuan; Sun, Ruili; Liu, Xueting; Jiang, Manli; Hu, Jinyue

    2015-01-01

    Chemokines and chemokine receptors are involved in the resolution or progression of renal diseases. Locally secreted chemokines mediated leukocyte recruitment during the initiation and amplification phase of renal inflammation. However, the regulation of chemokine induction is not fully understood. In this study, we found that IL-1 induced a significant up-regulation of CXC chemokines CXCL1, 2, and 8 at both mRNA and protein levels in human mesangial cells. The induction of chemokines was tolerant, as the pre-treatment of HMC with IL-1 down-regulated the induction of chemokines induced by IL-1 re-stimulation. IL-1 up-regulated the ubiquintin-editing enzyme A20. A20 over-expression down-regulated IL-1-induced up-regulation of chemokines, and A20 down-regulation reversed chemokine inhibition induced by IL-1 pre-treatment, suggested that A20 played important roles in the tolerant production of chemokines. Unexpectedly, A20 over- expression inhibited the activation of ERK, JNK, and P38, but did not inhibit the activation of NF-κB. In addition, both IL-1 treatment and A20 over-expression induced the degradation of IRAK1, an important adaptor for IL-1R1 signaling, and A20 inhibition by RNA interference partly reversed the degradation of IRAK1. Taken together, IL-1-induced A20 negatively regulated chemokine production, suggesting that A20 may be an important target for the prevention and control of kidney inflammation. PMID:26648169

  19. Epidemiology of traumatic spinal cord injury in Galicia, Spain: trends over a 20-year period.

    PubMed

    Montoto-Marqués, A; Ferreiro-Velasco, M E; Salvador-de la Barrera, S; Balboa-Barreiro, V; Rodriguez-Sotillo, A; Meijide-Failde, R

    2017-06-01

    Observational study with prospective and retrospective monitoring. To describe the epidemiological and demographic characteristics of traumatic spinal cord injury (TSCI), and to analyze its epidemiological changes. Unidad de Lesionados Medulares, Complejo Hospitalario Universitario A Coruña, in Galicia (Spain). The study included patients with TSCI who had been hospitalized between January 1995 and December 2014. Relevant data were extracted from the admissions registry and electronic health record. A total of 1195 patients with TSCI were admitted over the specified period of time; 76.4% male and 23.6% female. Mean patient age at injury was 50.20 years. Causes of injury were falls (54.2%), traffic accidents (37%), sports/leisure-related accidents (3.5%) and other traumatic causes (5.3%). Mean patient age increased significantly over time (from 46.40 to 56.54 years), and the number of cases of TSCI related to traffic accidents decreased (from 44.5% to 23.7%), whereas those linked to falls increased (from 46.9% to 65.6%). The most commonly affected neurological level was the cervical level (54.9%), increasing in the case of levels C1-C4 over time, and the most frequent ASIA (American Spinal Injury Association) grade was A (44.3%). The crude annual incidence rate was 2.17/100 000 inhabitants, decreasing significantly over time at an annual percentage rate change of -1.4%. The incidence rate of TSCI tends to decline progressively. Mean patient age has increased over time and cervical levels C1-C4 are currently the most commonly affected ones. These epidemiological changes will eventually result in adjustments in the standard model of care for TSCI.

  20. Comparison of Cardiovascular Risk Factors in Different Areas of Health Care Over a 20-Year Period

    PubMed Central

    Jardim, Thiago Veiga; Sousa, Ana Luiza Lima; Povoa, Thais Rolim; Barroso, Weimar Sebba; Chinem, Brunela; Jardim, Paulo Cesar Veiga

    2014-01-01

    Background Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Knowledge about cardiovascular risk factors (CVRFs) in young adults and their modification over time are measures that change the risks and prevent CVDs. Objectives To determine the presence of CVRFs and their changes in different health care professionals over a period of 20 years. Methods All students of medicine, nursing, nutrition, odontology, and pharmacy departments of Federal University of Goiás who agreed to participate in this study were evaluated when they started their degree courses and 20 years afterward. Questionnaires on CVRFs [systemic arterial hypertension (SAH), diabetes mellitus, dyslipidemia, and family history of early CVD, smoking, alcohol consumption, and sedentarism] were administered. Cholesterol levels, blood sugar levels, blood pressure, weight, height, and body mass index were determined. The Kolmogorov-Smirnov test was used to evaluate distribution, the chi-square test was used to compare different courses and sexes, and the McNemar test was used for comparing CVRFs. The significance level was set at a p value of < 0.05. Results The first stage of the study included 281 individuals (91% of all the students), of which 62.9% were women; the mean age was 19.7 years. In the second stage, 215 subjects were reassessed (76% of the initial sample), of which 59.07% were women; the mean age was 39.8 years. The sample mostly consisted of medical students (with a predominance of men), followed by nursing, nutrition, and pharmacy students, with a predominance of women (p < 0.05). Excessive weight gain, SAH, and dyslipidemia were observed among physicians and dentists (p < 0.05). Excessive weight gain and SAH and a reduction in sedentarism (p < 0.05) were observed among pharmacists. Among nurses there was an increase in excessive weight and alcohol consumption (p < 0.05). Finally, nutritionists showed an increase in dyslipidemia (p < 0.05). Conclusion In general

  1. The Evolution of Cloud Features on Neptune over a 20-day time period

    NASA Astrophysics Data System (ADS)

    Martin, S. C.; Roe, H.; de Pater, I.; Macintosh, B.; Gibbard, S.; Max, C. E.; Gavel, D.; Brown, M.; Ghez, A.

    2000-10-01

    Near-infrared images of Neptune were taken with SCAM, the slit-viewing camera of the AO/NIRSPEC system at the 10-m W.M. Keck II telescope, on 2000 June 8,17,18,22,23 and 29 UT. Observations with broad-band filter Nirspec-5 [1.61 micron], Nirspec-6 [1.93 micron], and K' [2.12 micron], and several narrow-band filters between 1.279 and 1.702 microns are compared to determine the temporal evolution of cloud features over the 20-day period. These images taken with the Keck Adaptive Optics system are spectacular, revealing narrow zonal bands at 3-4 degree latitude spacings within bright regions and near the equator. There are three regions of latitude that contain bright features along zonal bands. The dimmest of these bright regions is located in the Northern hemisphere and extends from 20 deg N to 40 deg N. The remaining two bright regions are located in the Southern hemisphere extending from 20 deg S to 50 deg S, and from 60 deg S to 70 deg S. The region near the South pole (a recently quiet location) contains a bright teardrop-shaped feature which may be related to the Westerly jet observed by Voyager and reported by Sanjay et.al. (Journal of Geophysical Research, vol.6, pp. 18941-18960, 1991) at a similar latitude. This research was supported in part by the STC Program of the National Science Foundation under Agreement No. AST-9876783, and in part under the auspices of the US Department of Energy at Lawrence Livermore National Laboratory, Univ. of Calif. under contract No. W-7405-Eng-48. Data presented herein were obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W.M. Keck Foundation.

  2. Incidence of Hepatitis C Infection among Prisoners by Routine Laboratory Values during a 20-Year Period

    PubMed Central

    Marco, Andrés; Gallego, Carlos; Caylà, Joan A.

    2014-01-01

    Background To estimate the incidence of Hepatitis C virus (HCV) and the predictive factors through repeated routine laboratory analyses. Methods An observational cohort study was carried out in Quatre Camins Prison, Barcelona. The study included subjects with an initial negative HCV result and routine laboratory analyses containing HCV serology from 1992 to 2011. The incidence of infection was calculated for the study population and for sub-groups by 100 person-years of follow-up (100 py). The predictive factors were determined through Kaplan-Meier curves and a Cox regression. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Results A total of 2,377 prisoners were included with a median follow-up time of 1,540.9 days per patient. Among the total population, 117 HCV seroconversions were detected (incidence of 1.17/100 py). The incidence was higher between 1992 and 1995 (2.57/100 py), among cases with HIV co-infection (8.34/100 py) and among intravenous drug users (IDU) without methadone treatment (MT) during follow-up (6.66/100 py). The incidence rate of HCV seroconversion among cases with a history of IDU and current MT was 1.35/100 py, which is close to that of the total study population. The following variables had a positive predictive value for HCV infection: IDU (p<0.001; HR = 7,30; CI: 4.83–11.04), Spanish ethnicity (p = 0.009; HR = 2,03; CI: 1.93–3.44) and HIV infection (p = 0.015; HR = 1.97; CI: 1.14–3.39). Conclusion The incidence of HCV infection among prisoners was higher during the first part of the study and among IDU during the entire study period. Preventative programs should be directed toward this sub-group of the prison population. PMID:24587394

  3. A 20 ampere shunt regulator for controlling individual magnets in a seriesed string

    SciTech Connect

    Martin, E.J.; Dobeck, N.; Jones, G.S.; O`Sullivan, M.K.

    1996-08-01

    At the CEBAF accelerator, groups of dipole magnets are often connected together in series and powered from a single large constant-current regulated D-C supply, referred to locally as a {open_quotes}box{close_quotes} supply. Besides the economy realized, this configuration promotes correct field tracking of all elements of a beam transport channel. However, it is often desirable to vary the current in one element of a string independently of the others, particularly at the entrance and exits of transport channels. A 20 ampere programmable current shunt is described. Installed in parallel with the desired magnet, it permits shunting (bypassing) up to 5% of the string current around that magnet. The shunt regulator consists of a bank of MOSFET power transistors operated in linear mode. Regulation of current through the passbank is obtained by feedback from a manganin shunt maintained at a constant temperature for stability. The module is designed for remote operation and provides readbacks of various parameters useful for maintenance. To achieve complete electrical isolation, an onboard microprocessor provides remote communications via an opto-isolated serial data link. Constructional details and initial operating experience with the plug-in shunt are described.

  4. A20 negatively regulates T cell receptor signaling to NF-kappaB by cleaving Malt1 ubiquitin chains.

    PubMed

    Düwel, Michael; Welteke, Verena; Oeckinghaus, Andrea; Baens, Mathijs; Kloo, Bernhard; Ferch, Uta; Darnay, Bryant G; Ruland, Jürgen; Marynen, Peter; Krappmann, Daniel

    2009-06-15

    The Carma1-Bcl10-Malt1 signaling module bridges TCR signaling to the canonical IkappaB kinase (IKK)/NF-kappaB pathway. Covalent attachment of regulatory ubiquitin chains to Malt1 paracaspase directs TCR signaling to IKK activation. Further, the ubiquitin-editing enzyme A20 was recently suggested to suppress T cell activation, but molecular targets for A20 remain elusive. In this paper, we show that A20 regulates the strength and duration of the IKK/NF-kappaB response upon TCR/CD28 costimulation. By catalyzing the removal of K63-linked ubiquitin chains from Malt1, A20 prevents sustained interaction between ubiquitinated Malt1 and the IKK complex and thus serves as a negative regulator of inducible IKK activity. Upon T cell stimulation, A20 is rapidly removed and paracaspase activity of Malt1 has been suggested to cleave A20. Using antagonistic peptides or reconstitution of Malt1(-/-) T cells, we show that Malt1 paracaspase activity is required for A20 cleavage and optimal IL-2 production, but dispensable for initial IKK/NF-kappaB signaling in CD4(+) T cells. However, proteasomal inhibition impairs A20 degradation and impedes TCR/CD28-induced IKK activation. Taken together, A20 functions as a Malt1 deubiquitinating enzyme and proteasomal degradation and de novo synthesis of A20 contributes to balance TCR/CD28-induced IKK/NF-kappaB signaling.

  5. Detecting land cover change over a 20 year time period in the Niagara Escarpment Plan using satellite remote sensing

    NASA Astrophysics Data System (ADS)

    Waite, Holly

    The Niagara Escarpment is one of Southern Ontario's most important landscapes. Due to the nature of the landform and its location, the Escarpment is subject to various development pressures including urban expansion, mineral resource extraction, agricultural practices and recreation. In 1985, Canada's first large scale environmentally based land use plan was put in place to ensure that only development that is compatible with the Escarpment occurred within the Niagara Escarpment Plan (NEP). The southern extent of the NEP is of particular interest in this study, since a portion of the Plan is located within the rapidly expanding Greater Toronto Area (GTA). The Plan area located in the Regional Municipalities of Hamilton and Halton represent both urban and rural geographical areas respectively, and are both experiencing development pressures and subsequent changes in land cover. Monitoring initiatives on the NEP have been established, but have done little to identify consistent techniques for monitoring land cover on the Niagara Escarpment. Land cover information is an important part of planning and environmental monitoring initiatives. Remote sensing has the potential to provide frequent and accurate land cover information over various spatial scales. The goal of this research was to examine land cover change in the Regional Municipalities of Hamilton and Halton portions of the NEP. This was achieved through the creation of land cover maps for each region using Landsat 5 Thematic Mapper (TM) remotely sensed data. These maps aided in determining the qualitative and quantitative changes that had occurred in the Plan area over a 20 year time period from 1986 to 2006. Change was also examined based on the NEP's land use designations, to determine if the Plan policy has been effective in protecting the Escarpment. To obtain land cover maps, five different supervised classification methods were explored: Minimum Distance, Mahalanobis Distance, Maximum Likelihood, Object

  6. Regulation of the human SLC25A20 expression by peroxisome proliferator-activated receptor alpha in human hepatoblastoma cells

    SciTech Connect

    Tachibana, Keisuke; Takeuchi, Kentaro; Inada, Hirohiko; Yamasaki, Daisuke; Ishimoto, Kenji; Tanaka, Toshiya; Hamakubo, Takao; Sakai, Juro; Kodama, Tatsuhiko; Doi, Takefumi

    2009-11-20

    Solute carrier family 25, member 20 (SLC25A20) is a key molecule that transfers acylcarnitine esters in exchange for free carnitine across the mitochondrial membrane in the mitochondrial {beta}-oxidation. The peroxisome proliferator-activated receptor alpha (PPAR{alpha}) is a ligand-activated transcription factor that plays an important role in the regulation of {beta}-oxidation. We previously established tetracycline-regulated human cell line that can be induced to express PPAR{alpha} and found that PPAR{alpha} induces the SLC25A20 expression. In this study, we analyzed the promoter region of the human slc25a20 gene and showed that PPAR{alpha} regulates the expression of human SLC25A20 via the peroxisome proliferator responsive element.

  7. Effect of external periodic regulations on Brownian motor

    NASA Astrophysics Data System (ADS)

    Yu, Lilong; Chen, Ruyin; Nie, Linru

    2015-01-01

    Effect of external periodic regulations on a symmetric Brownian motor performing between two temperature sources was investigated. By means of numerical calculations, we found that: (i) The regulations can control magnitude and direction of the motor's current to a large degree. As one of the motor's compartments is regulated, the motor's current can be both inversed and maximized, dependent on amplitude and frequency of the periodic driving force. If two periodic driving forces with identical amplitudes and frequencies are employed to regulate respectively two compartments of the Brownian motor, the current's magnitude and direction will make periodic oscillations with phase difference between them. In addition, the external periodic regulation can also change direction of thermal rectifier of the system as a switch. (ii) Optimal regulating parameters of the external periodic forces can enhance pronouncedly conversion efficiency of energy of the Brownian motor.

  8. A20 is a negative regulator of BCL10- and CARMA3-mediated activation of NF-kappaB.

    PubMed

    Stilo, Romania; Varricchio, Ettore; Liguoro, Domenico; Leonardi, Antonio; Vito, Pasquale

    2008-04-15

    The molecular complex containing CARMA proteins, BCL10 and TRAF6 has been identified recently as a key component in the signal transduction pathways that regulate activation of the nuclear factor kappaB (NF-kappaB) transcription factor. Here, we report that the inducible protein A20 negatively regulates these signaling cascades by means of its deubiquitylation activity. We show that A20 perturbs assembly of the complex containing CARMA3, BCL10 and IKKgamma/NEMO, thereby suppressing activation of NF-kappaB. Together, our results further define the molecular mechanisms that control activation of NF-kappaB and reveal a function for A20 in the regulation of CARMA and BCL10 activity in lymphoid and non-lymphoid cells.

  9. Frequent Down Regulation of the Tumor Suppressor Gene A20 in Multiple Myeloma

    PubMed Central

    Lassnig, Markus; Pursche, Beata; Steinbauer, Elisabeth; Wiltgen, Marco; Zulus, Barbara; Renner, Wilfried; Beham-Schmid, Christine

    2015-01-01

    Multiple myeloma (MM) is a malignant clonal expansion of plasma cells in the bone marrow and belongs to the mature B-cell neoplams. The pathogenesis of MM is associated with constitutive NF-κB activation. However, genetic alterations causing constitutive NF-κB activation are still incompletely understood. Since A20 (TNFAIP3) is a suppressor of the NF-κB pathway and is frequently inactivated in various lymphoid malignancies, we investigated the genetic and epigenetic properties of A20 in MM. In total, of 46 patient specimens analyzed, 3 single base pair exchanges, 2 synonymous mutations and one missense mutation were detected by direct sequencing. Gene copy number analysis revealed a reduced A20 gene copy number in 8 of 45 (17.7%) patients. Furthermore, immunohistochemical staining confirmed that A20 expression correlates with the reduction of A20 gene copy number. These data suggest that A20 contributes to tumor formation in a significant fraction of myeloma patients. PMID:25856582

  10. Reports of child sexual abuse of boys and girls: Longitudinal trends over a 20-year period in Victoria, Australia.

    PubMed

    Mathews, Ben; Bromfield, Leah; Walsh, Kerryann; Cheng, Qinglu; Norman, Rosana E

    2017-02-17

    Although prevalence studies show girls are more frequently sexually abused than boys, a significant proportion of boys also experience child sexual abuse (CSA). The challenges for public policy are amplified for boys due to less developed public and professional sensitisation to boys' experiences, conceptions of masculinity, and less research on boys including into reporting trends and outcomes. We conducted a 20-year longitudinal time-trend analysis of government data to identify reporting trends and report outcomes for CSA in Victoria, Australia from 1993 to 2012. We stratified by child gender and reporter status. Results indicate a new sensitisation to CSA, especially for boys, although this trend was not stable. Marked change occurred in the last five years, likely influenced by major social and political events. Comparison over time revealed that from 1993 to 2012, the rate of reporting of boys increased 2.6-fold whereas there was a 1.5-fold increase for girls. Comparing genders, with regards to rate of reporting, in 1993, the sex ratio of girls to boys was 2:1, while by 2012 this ratio changed to 1.14:1. Reports by police and other mandated reporters accounted for the majority of the increase in reports over the 20-year period, suggesting unequal sensitisation. Positive report outcomes (i.e. substantiations, findings of harm, and referral to services) increased twelve-fold for boys, and nearly five-fold for girls, indicating the increased levels of reports were based in actual clinical need. Most of this increase occurred from 2009 to 2012, influenced by a compound of social, political and agency-related factors.

  11. A20 Functional Domains Regulate Subcellular Localization and NF-Kappa B Activation

    DTIC Science & Technology

    2013-08-15

    development and prognosis of specific autoimmune diseases such as lupus , rheumatoid arthritis, and psoriasis (12, 62). It is of interest to note that A20...of investigators at the Bastholm laboratory of the Danish Cancer Society Research Center (44). A 1996 publication by this group demonstrated that

  12. Primary structure and androgen regulation of a 20-kilodalton protein specific to rat ventral prostate.

    PubMed

    Ho, K C; Snoek, R; Quarmby, V; Viskochil, D H; Rennie, P S; Wilson, E M; French, F S; Bruchovsky, N

    1989-07-25

    Nuclear and cytosolic forms of a 20-kdalton rat ventral prostate protein were purified and partially sequenced from their N-termini. Isolated nuclei were treated with micrococcal nuclease and extracted in 0.6 M NaCl, and proteins were separated by affinity chromatography on Matrex gel green A, ammonium sulfate fractionation, and fast protein liquid chromatography on Superose 12. The 43 amino acid N-terminal sequence of the nuclear 20-kdalton protein was identical with the cytosolic protein except it lacked 7 N-terminal amino acids present in the cytosolic form. The DNA sequence of a full-length complementary DNA clone isolated from a ventral prostate gt11 library extended the N-terminal sequence of the cytosolic form by an additional nine amino acids from the predicted initiation methionine. The cDNA included the nucleotide sequence for the 43 amino acid N-terminal sequence of the purified 20-kdalton protein and predicted molecular weights of 16,686, 17,521, and 18,650, respectively, for the nuclear, cytoplasmic, and nonprocessed proteins. Northern blot analyses of reproductive tract tissue RNAs using the 20-kdalton protein cDNA as probe revealed a single mRNA species of 0.92 kb detectable only in extracts of rat ventral prostate. Expression of the 0.92-kb mRNA was androgen dependent since the mRNA was undetectable in extracts obtained 4 days after castration and was restored 16 h after restimulation with androgen.

  13. 77 FR 41728 - Plan for Periodic Review of Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-16

    ...The Regulatory Flexibility Act (RFA) requires that the National Marine Fisheries Service (NMFS) periodically review existing regulations that have a significant economic impact on a substantial number of small entities, such as small businesses, small organizations, and small governmental jurisdictions. This plan describes how NMFS will perform this review and describes the regulations that are being proposed for review during the current review-cycle.

  14. Zinc-finger protein A20, a regulator of inflammation and cell survival, has de-ubiquitinating activity.

    PubMed Central

    Evans, Paul C; Ovaa, Huib; Hamon, Maureen; Kilshaw, Peter J; Hamm, Svetlana; Bauer, Stefan; Ploegh, Hidde L; Smith, Trevor S

    2004-01-01

    Ubiquitination regulates the stability and/or activity of numerous cellular proteins. The corollary is that de-ubiquitinating enzymes, which 'trim' polyubiquitin chains from specific substrate proteins, play key roles in controlling fundamental cellular activities. Ubiquitin is essential at several stages during the activation of NF-kappaB (nuclear factor kappaB), a central co-ordinator of inflammation and other immune processes. Ubiquitination is known to cause degradation of the inhibitory molecule IkappaBalpha (inhibitor of kappaB). In addition, activation of TRAF (tumour-necrosis-factor-receptor-associated factor) and IKKgamma (IkappaB kinase gamma)/NEMO (NF-kappaB essential modifier) signal adaptors relies on their modification with 'nonclassical' forms of polyubiquitin chains. Ubiquitin also plays a key role in determining cell fate by modulating the stability of numerous pro-apoptotic or anti-apoptotic proteins. The zinc-finger protein A20 has dual functions in inhibiting NF-kappaB activation and suppressing apoptosis. The molecular mechanisms of these anti-inflammatory and cytoprotective effects are unknown. Here we demonstrate that A20 is a de-ubiquitinating enzyme. It contains an N-terminal catalytic domain that belongs to the ovarian-tumour superfamily of cysteine proteases. A20 cleaved ubiquitin monomers from branched polyubiquitin chains linked through Lys48 or Lys63 and bound covalently to a thiol-group-reactive, ubiquitin-derived probe. Mutation of a conserved cysteine residue in the catalytic site (Cys103) abolished these activities. A20 did not have a global effect on ubiquitinated cellular proteins, which indicates that its activity is target-specific. The biological significance of the catalytic domain is unknown. PMID:14748687

  15. [Changes in the demand for paediatric neurology care in a spanish tertiary care hospital over a 20-year period].

    PubMed

    Monge Galindo, L; López-Pisón, J; Samper Villagrasa, P; Peña Segura, J L

    2014-01-01

    The purpose of this study is to determine the profile of the demand for paediatric neurology care in a Spanish tertiary hospital over the past 20 years. We studied epidemiological data, reasons for consultation, diagnoses and complementary tests from all patients examined by our Paediatric Neurology Unit in its 20 years of service (from May 1990 to March 2010). We also reviewed data from patients whose first visit took place within the last five years (2005-2010) and compared them to data obtained from a prior study carried out in this Unit from 1990 to 1995. To compare the first 5 years (group 1) with the last 5 years (group 2), we calculated confidence intervals, P<.05, for the frequency distribution (%) in each category. Main reasons for consultation and principal diagnoses for the 12726 patients evaluated in the 20-year period, as well as results from group 1 (2046 patients) and group 2 (4488 patients) corresponding to first and the last 5 years of activity respectively, are presented with their confidence intervals in a series of tables. Variations in the reasons for consultation, diagnoses and complementary tests over time reflect changes determined by medical, scientific and social progress, and organisational changes specific to each hospital. This explains the difficulty of comparing different patient series studied consecutively, which are even more pronounced between different hospitals. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  16. Screening for tuberculosis in family and household contacts in a rural area in Ethiopia over a 20-month period.

    PubMed

    Ramos, Jose Manuel; Biru, Dejere; Tesfamariam, Abraham; Reyes, Francisco; Górgolas, Miguel

    2013-12-01

    The purpose of this study is to describe the experience of the completion of the Tuberculosis (TB) Contact Screening Logbook (TB-CSL). The TB-CSL was retrospectively analyzed from July 2007 until June 2012. During the study period, 122 patients were included in the TB-CSL; however, 17 (13.9%) patients with TB were written in the TB-CSL, but without registering any contacts. Of the 105 TB patients with contacts registered, the family and household contacts were finally performed in 68 index TB patients (55.7% of TB patients). These 68 index TB cases had 299 family and household contacts; the median contact per patient was 4.4 (±1.9). Of the 299 contacts, 160 (53.5%) were screened. The median of those screened per patient was 2.3 (±1.9). Of the 160 family and household contacts screened, 34 (31.3%) of them were children ⩽5years of age. TB was diagnosed after screening in 16 (10.1%) contacts. Isoniazid preventive therapy was prescribed in 22 of 34 (64%) children <5years of age. Alternative methods should be implemented in rural areas to improve TB screening contacts, especially in children under 5years of age.

  17. Recurrent carcinoma of the head and neck: treatment strategies and survival analysis in a 20-year period.

    PubMed

    Eckardt, A; Barth, E L; Kokemueller, H; Wegener, G

    2004-04-01

    Following clinical diagnosis of a recurrent tumor, curative treatment is seldom available. Depending on the size of the recurrent tumor and the patient's general health condition extensive surgical resections and reconstructions are avoided in favor of non-surgical palliative intended treatment modalities. According to the literature location of the tumor, tumor size, as well as R-1- and R-2-resection rates are the most frequent reasons for the development of recurrent tumors. In a retrospective evaluation a population of 1000 patients who were treated for a primary head and neck cancer during the period from 1979 to 1996 were analysed descriptively. Survival probabilities of patients with recurrent tumors were calculated according to the product-limit method by Kaplan-Meier, different treatment concepts were compared and analysed with the log-rank test for significant differences. The largest proportion of primary tumors involved the floor of mouth ( n = 369, 36.9%). A total of 198 patients (19.8%) developed a recurrent cancer; 79.8% of patients experienced a recurrent cancer within two years following primary treatment. Within the group of T1/T2 tumors the incidence of recurrent tumors was 28.9%, whereas the incidence in the T3/T4 group was 44.6%. Tumor infiltration of the resection margins was detected in 12.9%. In line with the literature, tumor infiltration of the resection margins is a relevant prognostic factor, therefore intraoperative frozen section must be recommended. Treatment with curative intention, in particular extensive surgical resections, is seldom possible, and requires always a very intensive discussion with the patient.

  18. A20 is an early responding negative regulator of Toll-like receptor 5 signalling in intestinal epithelial cells during inflammation.

    PubMed

    Oshima, N; Ishihara, S; Rumi, M A K; Aziz, M M; Mishima, Y; Kadota, C; Moriyama, I; Ishimura, N; Amano, Y; Kinoshita, Y

    2010-02-01

    Several negative regulatory mechanisms control Toll-like receptor (TLR)-mediated inflammatory responses and restore immune system balance, including the zinc-finger protein A20, a negative regulator of TLR signalling that inhibits nuclear factor kappa B (NF-kappaB) activity. In the present study, we investigated TLR-5-mediated A20 expression and its role in intestinal epithelial cells (IECs) during inflammation. HCT-15 and HT-29 cells were stimulated with flagellin, then the expressions of A20, interleukin-1 receptor-associated kinase (IRAK-M) and Tollip were evaluated using RNase protection assay. Furthermore, experimental colitis was induced in tlr4-deficient CH3/HeJ mice by administration of dextran sodium sulphate (DSS), then flagellin was injected anally, and the colonic expression of A20 was examined by real-time polymerase chain reaction (PCR) and immunohistochemistry. To confirm flagellin-induced expression of A20, we employed an organ culture system. The role of A20 in flagellin-induced tolerance induction was evaluated in vitro, using a gene knock-down method targeting A20. A20 expression increased rapidly and peaked at 1 h after flagellin stimulation in cultured IECs, then declined gradually to the basal level. In vivo, anal injection of flagellin induced epithelial expression of A20 in injured colonic tissue, whereas flagellin did not cause a significant increase in A20 expression in non-injured normal tissue, which was also confirmed in vitro using the organ culture system. Gene knock-down using A20 siRNA did not influence tolerance induced by restimulation with flagellin. A20 is an early response negative regulator of TLR-5 signalling in IECs that functions during intestinal inflammation. Our results provide new insights into the negative feedback regulation of TLR-5 signalling that maintains the innate immune system in the gut.

  19. A20 is an early responding negative regulator of Toll-like receptor 5 signalling in intestinal epithelial cells during inflammation

    PubMed Central

    Oshima, N; Ishihara, S; Rumi, M A K; Aziz, M M; Mishima, Y; Kadota, C; Moriyama, I; Ishimura, N; Amano, Y; Kinoshita, Y

    2010-01-01

    Several negative regulatory mechanisms control Toll-like receptor (TLR)-mediated inflammatory responses and restore immune system balance, including the zinc-finger protein A20, a negative regulator of TLR signalling that inhibits nuclear factor kappa B (NF-κB) activity. In the present study, we investigated TLR-5-mediated A20 expression and its role in intestinal epithelial cells (IECs) during inflammation. HCT-15 and HT-29 cells were stimulated with flagellin, then the expressions of A20, interleukin-1 receptor-associated kinase (IRAK-M) and Tollip were evaluated using RNase protection assay. Furthermore, experimental colitis was induced in tlr4-deficient CH3/HeJ mice by administration of dextran sodium sulphate (DSS), then flagellin was injected anally, and the colonic expression of A20 was examined by real-time polymerase chain reaction (PCR) and immunohistochemistry. To confirm flagellin-induced expression of A20, we employed an organ culture system. The role of A20 in flagellin-induced tolerance induction was evaluated in vitro, using a gene knock-down method targeting A20. A20 expression increased rapidly and peaked at 1 h after flagellin stimulation in cultured IECs, then declined gradually to the basal level. In vivo, anal injection of flagellin induced epithelial expression of A20 in injured colonic tissue, whereas flagellin did not cause a significant increase in A20 expression in non-injured normal tissue, which was also confirmed in vitro using the organ culture system. Gene knock-down using A20 siRNA did not influence tolerance induced by restimulation with flagellin. A20 is an early response negative regulator of TLR-5 signalling in IECs that functions during intestinal inflammation. Our results provide new insights into the negative feedback regulation of TLR-5 signalling that maintains the innate immune system in the gut. PMID:19912257

  20. Regulation of period 1 expression in cultured rat pineal

    NASA Technical Reports Server (NTRS)

    Fukuhara, Chiaki; Dirden, James C.; Tosini, Gianluca

    2002-01-01

    The aim of the present study was to investigate the in vitro expression of Period 1 (Per1), Period 2 (Per2) and arylalkylamine N-acetyltransferase (AA-NAT) genes in the rat pineal gland to understand the mechanism(s) regulating the expression of these genes in this organ. Pineals, when maintained in vitro for 5 days, did not show circadian rhythmicity in the expression of any of the three genes monitored. Norepinephrine (NE) induced AA-NAT and Per1, whereas its effect on Per2 was negligible. Contrary to what was observed in other systems, NE stimulation did not induce circadian expression of Per1. The effect of NE on Per1 level was dose- and receptor subtype-dependent, and both cAMP and cGMP induced Per1. Per1 was not induced by repeated NE - or forskolin - stimulation. Protein synthesis was not necessary for NE-induced Per1, but it was for reduction of Per1 following NE stimulation. Per1 transcription in pinealocytes was activated by BMAL1/CLOCK. Our results indicate that important differences are present in the regulation of these genes in the mammalian pineal. Copyright 2002 S. Karger AG, Basel.

  1. Regulation of period 1 expression in cultured rat pineal

    NASA Technical Reports Server (NTRS)

    Fukuhara, Chiaki; Dirden, James C.; Tosini, Gianluca

    2002-01-01

    The aim of the present study was to investigate the in vitro expression of Period 1 (Per1), Period 2 (Per2) and arylalkylamine N-acetyltransferase (AA-NAT) genes in the rat pineal gland to understand the mechanism(s) regulating the expression of these genes in this organ. Pineals, when maintained in vitro for 5 days, did not show circadian rhythmicity in the expression of any of the three genes monitored. Norepinephrine (NE) induced AA-NAT and Per1, whereas its effect on Per2 was negligible. Contrary to what was observed in other systems, NE stimulation did not induce circadian expression of Per1. The effect of NE on Per1 level was dose- and receptor subtype-dependent, and both cAMP and cGMP induced Per1. Per1 was not induced by repeated NE - or forskolin - stimulation. Protein synthesis was not necessary for NE-induced Per1, but it was for reduction of Per1 following NE stimulation. Per1 transcription in pinealocytes was activated by BMAL1/CLOCK. Our results indicate that important differences are present in the regulation of these genes in the mammalian pineal. Copyright 2002 S. Karger AG, Basel.

  2. Time trends in upper gastrointestinal diseases and Helicobacter pylori infection in a multiracial Asian population--a 20-year experience over three time periods.

    PubMed

    Leow, A H-R; Lim, Y-Y; Liew, W-C; Goh, K-L

    2016-04-01

    Marked epidemiological changes in upper gastrointestinal diseases and Helicobacter pylori infection have taken place in the Asian Pacific region. In particular, differences with respect to race in the multiracial Asian population in Malaysia have been important and interesting. A time trend study of upper gastrointestinal disease and H. pylori infection in three time periods: 1989-1990, 1999-2000 and 2009-2010 spanning a period of 20 years was carried out. Consecutive first time gastroscopies carried out on patients attending the University of Malaya Medical Center were studied. Diagnoses and H. pylori infection status were carefully recorded. A steady decline in prevalence of duodenal ulcer (DU) and gastric ulcer (GU) from 21.1% to 9.5% to 5.0% and from 11.9% to 9.4% to 9.9% while an increase in erosive oesophagitis (EO) from 2.0% to 8.4% to 9.5% (chi-square for trend; P < 0.001) for the periods 1989-1990, 1999-200 and 2009-2010 were observed. The overall prevalence of H. pylori had also decreased from 51.7% to 30.3% to 11.1% for the same periods of time. The proportion of H. pylori positive ulcers had also decreased: DU (90.1%-69.8%-28.9%) and GU (86.6-56.8%-18.9%) (P < 0.001). This was observed in Malays, Chinese and Indians but the difference over time was most marked in Malays. There was a steady decline in the proportion of patients with gastric and oesophageal cancers. Peptic ulcers have declined significantly over a 20-year period together with a decline in H. pylori infection. In contrast, a steady increase in erosive oesophagitis was observed. Gastric and oesophageal squamous cell cancers have declined to low levels. © 2016 John Wiley & Sons Ltd.

  3. Relation of Smoking, Drinking and Physical Activity to Changes in Vision Over a 20-Year Period: The Beaver Dam Eye Study

    PubMed Central

    Klein, Ronald; Lee, Kristine E.; Gangnon, Ronald E.; Klein, Barbara E. K.

    2014-01-01

    Objective To describe relationships of lifestyle characteristics to changes in vision and incidence of visual impairment (VI) over a 20-year period in the Beaver Dam Eye Study (BDES). Design Longitudinal population-based cohort study. Participants A cohort of 4926 persons aged 43–86 years participated at the baseline examinations in 1988–1990, and 3721, 2962, 2375, and 1913 participated in follow-up examinations in 1993–1995, 1998–2000, 2003–2005, and 2008–2010, respectively. Methods Best corrected visual acuity measured by a modified Early Treatment Diabetic Retinopathy Study protocol. Main Outcome Measure Change in number of letters read correctly and incidence of VI based on best-corrected visual acuity in the better eye assessed at each examination over 20-year period. Results The 20-year cumulative incidence of VI was 5.4%. There was a mean loss of 1.6 letters between exams with a 20-year loss of 6.6 letters. While adjusting for age, income, and age-related macular degeneration (AMD) severity, being a current or past smoker was related to greater change in the numbers of letters lost. Persons who had not consumed alcoholic beverages over the past year and sedentary persons had higher odds of incident VI than persons who drank occasionally or who were physically active. For example, in women with early AMD and annual household income less than $10,000, the estimated 20-year cumulative incidence of VI in those who drank occasionally and were physically active was 5.9% compared to 25.8% in women who had not consumed alcoholic beverages over the past year and were sedentary. Conclusions Three modifiable behaviors, smoking, drinking alcohol, and physical activity were associated with changes in vision. Further evidence that changes in these behaviors will result in less loss of vision is needed because of the expected increase in the burden of VI due to the aging of the population. PMID:24594095

  4. Remission of CVB3-induced myocarditis with Astragaloside IV treatment requires A20 (TNFAIP3) up-regulation

    PubMed Central

    Gui, Jun; Chen, Ruizhen; Xu, Wei; Xiong, Sidong

    2015-01-01

    Viral myocarditis (VMC) most prevalently caused by coxsackievirus B3 (CVB3) infection is characterized by severe cardiac inflammation. Therapeutic options for the disease are still limited. Astragaloside IV (AST-IV), a purified small molecular saponin (C41H68O14, MW 784), is the main active component of Chinese medical herb Astragalus which has been empirically prescribed for the treatment of heart dysfunction for centuries. In this study, we investigated the effect of AST-IV on CVB3-induced myocarditis and explored its possible mechanism involved. The results showed that AST-IV administration alleviated the severity of myocarditis and attenuated cardiac inflammation, which was mediated by inhibition of nuclear factor-kappaB (NF-κB) signalling. Importantly, we further identified that the inhibitory effect of AST-IV on NF-κB signalling was through increasing A20 (TNFAIP3) expression. Moreover, we validated that A20 was critical for the therapeutic efficacy of AST-IV on CVB3-induced myocarditis. Finally, we revealed that AST-IV enhanced A20 expression at post-transcriptional level by stabilization of mRNA. Our findings uncover a previously unknown mechanism for AST-IV in the treatment of VMC because of modulating inflammatory response via increasing A20 expression, which provide a potential target for screening new drugs and are helpful for optimization of the therapeutic strategies for VMC. PMID:25728713

  5. Remission of CVB3-induced myocarditis with Astragaloside IV treatment requires A20 (TNFAIP3) up-regulation.

    PubMed

    Gui, Jun; Chen, Ruizhen; Xu, Wei; Xiong, Sidong

    2015-04-01

    Viral myocarditis (VMC) most prevalently caused by coxsackievirus B3 (CVB3) infection is characterized by severe cardiac inflammation. Therapeutic options for the disease are still limited. Astragaloside IV (AST-IV), a purified small molecular saponin (C41 H68 O14 , MW 784), is the main active component of Chinese medical herb Astragalus which has been empirically prescribed for the treatment of heart dysfunction for centuries. In this study, we investigated the effect of AST-IV on CVB3-induced myocarditis and explored its possible mechanism involved. The results showed that AST-IV administration alleviated the severity of myocarditis and attenuated cardiac inflammation, which was mediated by inhibition of nuclear factor-kappaB (NF-κB) signalling. Importantly, we further identified that the inhibitory effect of AST-IV on NF-κB signalling was through increasing A20 (TNFAIP3) expression. Moreover, we validated that A20 was critical for the therapeutic efficacy of AST-IV on CVB3-induced myocarditis. Finally, we revealed that AST-IV enhanced A20 expression at post-transcriptional level by stabilization of mRNA. Our findings uncover a previously unknown mechanism for AST-IV in the treatment of VMC because of modulating inflammatory response via increasing A20 expression, which provide a potential target for screening new drugs and are helpful for optimization of the therapeutic strategies for VMC.

  6. Depressive disorder in the last phase of life in patients with cardiovascular disease, cancer, and COPD: data from a 20-year follow-up period in general practice.

    PubMed

    Warmenhoven, Franca; Bor, Hans; Lucassen, Peter; Vissers, Kris; van Weel, Chris; Prins, Judith; Schers, Henk

    2013-05-01

    Depression is assumed to be common in chronically ill patients during their last phase of life and is associated with poorer outcomes. The prevalence of depression is widely varying in previous studies due to the use of different terminology, classification, and assessment methods. To explore the reported incidence of depressive disorder, as registered in the last phase of life of patients who died from cardiovascular disease, cancer or COPD, in a sample of primary care patients. A historic cohort study, using a 20-year period registration database of medical records in four Dutch general practices (a dynamic population based on the Continuous Morbidity Registration database). Medical history of the sample cohort was analysed for the diagnosis of a new episode of depressive disorder and descriptive statistics were used. In total 982 patients were included, and 19 patients (1.9%) were diagnosed with a new depressive disorder in the last year of their life. The lifetime prevalence of depressive disorder in this sample was 8.2%. The incidence of depressive disorder in the last phase of life is remarkably low in this study. These data were derived from actual patient care in general practice. Psychiatric diagnoses were made by GPs in the context of both patient needs and delivered care. A broader concept of depression in general practice is recommended to improve the diagnosis and treatment of mood disorders in patients in the last phase of life.

  7. Depressive disorder in the last phase of life in patients with cardiovascular disease, cancer, and COPD: data from a 20-year follow-up period in general practice

    PubMed Central

    Warmenhoven, Franca; Bor, Hans; Lucassen, Peter; Vissers, Kris; van Weel, Chris; Prins, Judith; Schers, Henk

    2013-01-01

    Background Depression is assumed to be common in chronically ill patients during their last phase of life and is associated with poorer outcomes. The prevalence of depression is widely varying in previous studies due to the use of different terminology, classification, and assessment methods. Aim To explore the reported incidence of depressive disorder, as registered in the last phase of life of patients who died from cardiovascular disease, cancer or COPD, in a sample of primary care patients. Design and setting A historic cohort study, using a 20-year period registration database of medical records in four Dutch general practices (a dynamic population based on the Continuous Morbidity Registration database). Method Medical history of the sample cohort was analysed for the diagnosis of a new episode of depressive disorder and descriptive statistics were used. Results In total 982 patients were included, and 19 patients (1.9%) were diagnosed with a new depressive disorder in the last year of their life. The lifetime prevalence of depressive disorder in this sample was 8.2%. Conclusion The incidence of depressive disorder in the last phase of life is remarkably low in this study. These data were derived from actual patient care in general practice. Psychiatric diagnoses were made by GPs in the context of both patient needs and delivered care. A broader concept of depression in general practice is recommended to improve the diagnosis and treatment of mood disorders in patients in the last phase of life. PMID:23643227

  8. Genetic relatedness of selected clinical Vibrio cholerae O139 isolates from the southern coastal area of China over a 20-year period.

    PubMed

    Li, B S; Xiao, Y; Wang, D C; Tan, H L; Ke, B X; He, D M; Ke, C W; Zhang, Y H

    2016-09-01

    Vibrio cholerae O139 emerged as a causative agent of epidemic cholera in 1992 in India and Bangladesh, and was subsequently reported in China in 1993. The genetic relatedness and molecular characteristics of V. cholerae O139 in Guangdong Province, located in the southern coastal area of China, remains undetermined. In this study, we investigated 136 clinical V. cholerae O139 isolates from 1993 to 2013 in Guangdong. By conventional PCR, 123 (90·4%) isolates were positive for ctxB, ace and zot. Sequencing of the positive amplicons indicated 113 (91·7%) isolates possessed the El Tor allele of ctxB (genotype 3); seven carried the classical ctxB type (genotype 1) and three harboured a novel ctxB type (genotype 5). With respect to tcpA, 123 (90·4%) isolates were positive for the El Tor allele. In addition, pulsed-field gel electrophoresis (with NotI digestion) differentiated the isolates into clusters A and B. Cluster A contained seven of the non-toxigenic isolates from 1998 to 2000; another six non-toxigenic isolates (from 1998 and 2007) and all of the toxigenic isolates formed cluster B. Our results suggest that over a 20-year period, the predominant O139 clinical isolates have maintained a relatively tight clonal structure, although some genetic variance and shift has occurred. Our data highlight the persistence of toxigenic V. cholerae O139 in clinical settings in the southern coastal area of China.

  9. Encoding NF-κB temporal control in response to TNF: distinct roles for the negative regulators IκBα and A20

    PubMed Central

    Werner, Shannon L.; Kearns, Jeffrey D.; Zadorozhnaya, Victoria; Lynch, Candace; O’Dea, Ellen; Boldin, Mark P.; Ma, Averil; Baltimore, David; Hoffmann, Alexander

    2008-01-01

    TNF-induced NF-κB activity shows complex temporal regulation whose different phases lead to distinct gene expression programs. Combining experimental studies and mathematical modeling, we identify two temporal amplification steps—one determined by the obligate negative feedback regulator IκBα—that define the duration of the first phase of NF-κB activity. The second phase is defined by A20, whose inducible expression provides for a rheostat function by which other inflammatory stimuli can regulate TNF responses. Our results delineate the nonredundant functions implied by the knockout phenotypes of iκbα and a20, and identify the latter as a signaling cross-talk mediator controlling inflammatory and developmental responses. PMID:18676814

  10. Determinants of Aortic Root Dilatation and Reference Values Among Young Adults Over a 20-Year Period: Coronary Artery Risk Development in Young Adults Study.

    PubMed

    Teixido-Tura, Gisela; Almeida, Andre L C; Choi, Eui-Young; Gjesdal, Ola; Jacobs, David R; Dietz, Harry C; Liu, Kiang; Sidney, Stephen; Lewis, Cora E; Garcia-Dorado, David; Evangelista, Artur; Gidding, Samuel; Lima, João A C

    2015-07-01

    Aortic size increases with age, but factors related to such dilatation in healthy young adult population have not been studied. We aim to evaluate changes in aortic dimensions and its principal correlates among young adults over a 20-year time period. Reference values for aortic dimensions in young adults by echocardiography are also provided. Healthy Coronary Artery Risk Development in Young Adults (CARDIA) study participants aged 23 to 35 years in 1990-1991 (n=3051) were included after excluding 18 individuals with significant valvular dysfunction. Aortic root diameter (ARD) by M-mode echocardiography at year-5 (43.7% men; age, 30.2 ± 3.6 years) and year-25 CARDIA exams was obtained. Univariable and multivariable analyses were performed to assess associations of ARD with clinical data at years-5 and -25. ARD from year-5 was used to establish reference values of ARD in healthy young adults. ARD at year-25 was greater in men (33.3 ± 3.7 versus 28.7 ± 3.4 mm; P<0.001) and in whites (30.9 ± 4.3 versus 30.5 ± 4.1 mm; P=0.006). On multivariable analysis, ARD at year-25 was positively correlated with male sex, white ethnicity, age, height, weight, 20-year gain in weight, active smoking at baseline, and 20-year increase in diastolic, systolic, and mean arterial pressure. A figure showing the estimated 95th percentile of ARD by age and body surface area stratified by race and sex is provided. This study demonstrates that smoking, blood pressure, and increase in body weight are the main modifiable correlates of aortic root dilation during young adulthood. Our study also provides reference values for ARD in young adults.

  11. Three-dimensional motion detection of a 20-nm gold nanoparticle using twilight-field digital holography with coherence regulation.

    PubMed

    Goto, Kazufumi; Hayasaki, Yoshio

    2015-07-15

    In the twilight-field method for obtaining interference fringes with high contrast in in-line digital holography, only the intensity of the reference light is regulated to be close to the intensity of the object light, which is the ultra-weak scattered light from a nanoparticle, by using a low-frequency attenuation filter. Coherence of the light also strongly affects the contrast of the interference fringes. High coherence causes a lot of undesired coherent noise, which masks the fringes derived from the nanoparticles. Too-low coherence results in fringes with low contrast and a correspondingly low signal-to-noise ratio. Consequently, proper regulation of the coherence of the light source, in this study the spectral width, improves the minimum detectable size in holographic three-dimensional position measurement of nanoparticles. By using these methods, we were able to measure the position of a gold nanoparticle with a minimum diameter of 20 nm.

  12. Does Cancer Literature Reflect Multidisciplinary Practice? A Systematic Review of Oncology Studies in the Medical Literature Over a 20-Year Period

    SciTech Connect

    Holliday, Emma B.; Ahmed, Awad A.; Yoo, Stella K.; Jagsi, Reshma; Hoffman, Karen E.

    2015-07-15

    Purpose: Quality cancer care is best delivered through a multidisciplinary approach requiring awareness of current evidence for all oncologic specialties. The highest impact journals often disseminate such information, so the distribution and characteristics of oncology studies by primary intervention (local therapies, systemic therapies, and targeted agents) were evaluated in 10 high-impact journals over a 20-year period. Methods and Materials: Articles published in 1994, 2004, and 2014 in New England Journal of Medicine, Lancet, Journal of the American Medical Association, Lancet Oncology, Journal of Clinical Oncology, Annals of Oncology, Radiotherapy and Oncology, International Journal of Radiation Oncology, Biology, Physics, Annals of Surgical Oncology, and European Journal of Surgical Oncology were identified. Included studies were prospectively conducted and evaluated a therapeutic intervention. Results: A total of 960 studies were included: 240 (25%) investigated local therapies, 551 (57.4%) investigated systemic therapies, and 169 (17.6%) investigated targeted therapies. More local therapy trials (n=185 [77.1%]) evaluated definitive, primary treatment than systemic (n=178 [32.3%]) or targeted therapy trials (n=38 [22.5%]; P<.001). Local therapy trials (n=16 [6.7%]) also had significantly lower rates of industry funding than systemic (n=207 [37.6%]) and targeted therapy trials (n=129 [76.3%]; P<.001). Targeted therapy trials represented 5 (2%), 38 (10.2%), and 126 (38%) of those published in 1994, 2004, and 2014, respectively (P<.001), and industry-funded 48 (18.9%), 122 (32.6%), and 182 (54.8%) trials, respectively (P<.001). Compared to publication of systemic therapy trial articles, articles investigating local therapy (odds ratio: 0.025 [95% confidence interval: 0.012-0.048]; P<.001) were less likely to be found in high-impact general medical journals. Conclusions: Fewer studies evaluating local therapies, such as surgery and radiation, are published in

  13. Does Cancer Literature Reflect Multidisciplinary Practice? A Systematic Review of Oncology Studies in the Medical Literature Over a 20-Year Period.

    PubMed

    Holliday, Emma B; Ahmed, Awad A; Yoo, Stella K; Jagsi, Reshma; Hoffman, Karen E

    2015-07-15

    Quality cancer care is best delivered through a multidisciplinary approach requiring awareness of current evidence for all oncologic specialties. The highest impact journals often disseminate such information, so the distribution and characteristics of oncology studies by primary intervention (local therapies, systemic therapies, and targeted agents) were evaluated in 10 high-impact journals over a 20-year period. Articles published in 1994, 2004, and 2014 in New England Journal of Medicine, Lancet, Journal of the American Medical Association, Lancet Oncology, Journal of Clinical Oncology, Annals of Oncology, Radiotherapy and Oncology, International Journal of Radiation Oncology, Biology, Physics, Annals of Surgical Oncology, and European Journal of Surgical Oncology were identified. Included studies were prospectively conducted and evaluated a therapeutic intervention. A total of 960 studies were included: 240 (25%) investigated local therapies, 551 (57.4%) investigated systemic therapies, and 169 (17.6%) investigated targeted therapies. More local therapy trials (n=185 [77.1%]) evaluated definitive, primary treatment than systemic (n=178 [32.3%]) or targeted therapy trials (n=38 [22.5%]; P<.001). Local therapy trials (n=16 [6.7%]) also had significantly lower rates of industry funding than systemic (n=207 [37.6%]) and targeted therapy trials (n=129 [76.3%]; P<.001). Targeted therapy trials represented 5 (2%), 38 (10.2%), and 126 (38%) of those published in 1994, 2004, and 2014, respectively (P<.001), and industry-funded 48 (18.9%), 122 (32.6%), and 182 (54.8%) trials, respectively (P<.001). Compared to publication of systemic therapy trial articles, articles investigating local therapy (odds ratio: 0.025 [95% confidence interval: 0.012-0.048]; P<.001) were less likely to be found in high-impact general medical journals. Fewer studies evaluating local therapies, such as surgery and radiation, are published in high-impact oncology and medicine literature. Further

  14. [The peculiarities of calcium metabolism regulation in different periods of growth and development].

    PubMed

    Moĭsa, S S; Nozdrachev, A D

    2014-01-01

    The review contains literature data about calcium metabolism regulation in different periods of growth and development. The analyses of retrospective and current sources of information about the regulation of calcium homeostasis under the theory of functional systems, the regulation of calcium metabolism in prenatal and postnatal periods of the development, the significance of calcium metabolism disturbances in the development of pathological conditions were showed.

  15. 78 FR 48123 - Federal Acquisition Regulation; Contractor Comment Period, Past Performance Evaluations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-07

    ...-AM40 Federal Acquisition Regulation; Contractor Comment Period, Past Performance Evaluations AGENCY... Acquisition Regulation (FAR) to implement provisions of law limiting the periods allowed for contractor..., and it starts the suspense period for contractor comment or rebuttal. It is important for past...

  16. 75 FR 69633 - Plan for Periodic Review of Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-15

    ... Chesapeake Bay, and the waters of the James River, York River, and Rappahannock River downstream of the first... overall (LOA) of a vessel for the purposes of the regulations governing the groundfish fisheries in the... owners in determining a vessel's LOA, and to further the goals and objectives of the FMP for...

  17. miR-125b regulates differentiation and metabolic reprogramming of T cell acute lymphoblastic leukemia by directly targeting A20

    PubMed Central

    Liu, Zixing; Smith, Kelly R.; Khong, Hung T.; Huang, Jingshan; Ahn, Eun-Young Erin; Zhou, Ming; Tan, Ming

    2016-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic malignancy. Although it has been reported that overexpression of miR-125b leads to T-ALL development, the underlying mechanisms of miR-125b action are still unclear. The goal of this study is to delineate the role of miR-125b in T-ALL development. We found that miR-125b is highly expressed in undifferentiated leukemic T cells (CD4-negative) while its expression is low in differentiated T cells (CD4-positive). Overexpression of miR-125b increased the CD4-negative population in T cells, whereas depletion of miR-125b by miR-125b-sponge decreased the CD4-negative cell population. We identified that A20 (TNFAIP3) is a direct target of miR-125b in T cells. Overexpression of miR-125b also increased glucose uptake and oxygen consumption in T cells through targeting A20. Furthermore, restoration of A20 in miR-125b-overexpressing cells decreased the CD4-negative population in T cell leukemia, and decreased glucose uptake and oxygen consumption to the basal level of T cells transfected with vector. In conclusion, our data demonstrate that miR-125b regulates differentiation and reprogramming of T cell glucose metabolism via targeting A20. Since both de-differentiation and dysregulated glucose metabolism contribute to the development of T-cell leukemia, these findings provide novel insights into the understanding and treatment of T-ALL. PMID:27637078

  18. Design & development fo a 20-MW flywheel-based frequency regulation power plant : a study for the DOE Energy Storage Systems program.

    SciTech Connect

    Rounds, Robert; Peek, Georgianne Huff

    2009-01-01

    This report describes the successful efforts of Beacon Power to design and develop a 20-MW frequency regulation power plant based solely on flywheels. Beacon's Smart Matrix (Flywheel) Systems regulation power plant, unlike coal or natural gas generators, will not burn fossil fuel or directly produce particulates or other air emissions and will have the ability to ramp up or down in a matter of seconds. The report describes how data from the scaled Beacon system, deployed in California and New York, proved that the flywheel-based systems provided faster responding regulation services in terms of cost-performance and environmental impact. Included in the report is a description of Beacon's design package for a generic, multi-MW flywheel-based regulation power plant that allows accurate bids from a design/build contractor and Beacon's recommendations for site requirements that would ensure the fastest possible construction. The paper concludes with a statement about Beacon's plans for a lower cost, modular-style substation based on the 20-MW design.

  19. 77 FR 6038 - Revisions to Distilled Spirits Plant Operations Reports and Regulations; Comment Period Extension

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-07

    ... Operations Reports and Regulations; Comment Period Extension AGENCY: Alcohol and Tobacco Tax and Trade Bureau, Treasury. ACTION: Notice of proposed rulemaking; extension of comment period. SUMMARY: The Alcohol and Tobacco Tax and Trade Bureau is extending the comment period for Notice No. 124, Revisions to Distilled...

  20. A 20-year period of orthotopic liver transplantation activity in a single center: a time series analysis performed using the R Statistical Software.

    PubMed

    Santori, G; Andorno, E; Morelli, N; Casaccia, M; Bottino, G; Di Domenico, S; Valente, U

    2009-05-01

    In many Western countries a "minimum volume rule" policy has been adopted as a quality measure for complex surgical procedures. In Italy, the National Transplant Centre set the minimum number of orthotopic liver transplantation (OLT) procedures/y at 25/center. OLT procedures performed in a single center for a reasonably large period may be treated as a time series to evaluate trend, seasonal cycles, and nonsystematic fluctuations. Between January 1, 1987 and December 31, 2006, we performed 563 cadaveric donor OLTs to adult recipients. During 2007, there were another 28 procedures. The greatest numbers of OLTs/y were performed in 2001 (n = 51), 2005 (n = 50), and 2004 (n = 49). A time series analysis performed using R Statistical Software (Foundation for Statistical Computing, Vienna, Austria), a free software environment for statistical computing and graphics, showed an incremental trend after exponential smoothing as well as after seasonal decomposition. The predicted OLT/mo for 2007 calculated with the Holt-Winters exponential smoothing applied to the previous period 1987-2006 helped to identify the months where there was a major difference between predicted and performed procedures. The time series approach may be helpful to establish a minimum volume/y at a single-center level.

  1. Periodization

    PubMed Central

    Lorenz, Daniel S.; Reiman, Michael P.; Walker, John C.

    2010-01-01

    Background: Clinicians are constantly faced with the challenge of designing training programs for injured and noninjured athletes that maximize healing and optimize performance. Periodization is a concept of systematic progression—that is, resistance training programs that follow predictable patterns of change in training variables. The strength training literature is abundant with studies comparing periodization schemes on uninjured, trained, and untrained athletes. The rehabilitation literature, however, is scarce with information about how to optimally design resistance training programs based on periodization principles for injured athletes. The purpose of this review is to discuss relevant training variables and methods of periodization, as well as periodization program outcomes. A secondary purpose is to provide an anecdotal framework regarding implementation of periodization principles into rehabilitation programs. Evidence Acquisition: A Medline search from 1979 to 2009 was implemented with the keywords periodization, strength training, rehabilitation, endurance, power, hypertrophy, and resistance training with the Boolean term AND in all possible combinations in the English language. Each author also undertook independent hand searching of article references used in this review. Results: Based on the studies researched, periodized strength training regimens demonstrate improved outcomes as compared to nonperiodized programs. Conclusions: Despite the evidence in the strength training literature supporting periodization programs, there is a considerable lack of data in the rehabilitation literature about program design and successful implementation of periodization into rehabilitation programs. PMID:23015982

  2. Relevance of EORTC Criteria for the Diagnosis of Invasive Aspergillosis in HIV-Infected Patients, and Survival Trends Over a 20-Year Period in France.

    PubMed

    Denis, Blandine; Guiguet, Marguerite; de Castro, Nathalie; Mechaï, Frédéric; Revest, Matthieu; Melica, Giovanna; Costagliola, Dominique; Lortholary, Olivier

    2015-10-15

    Before the advent of combination antiretroviral therapy (cART), roughly 50% of cases of invasive aspergillosis (IA) associated with human immunodeficiency virus (HIV) infection involved individuals without classical predisposing host factors, and the median survival time was <4 months after diagnosis. We examined if the situation evolved over time using the revised European Organisation for Research and Treatment of Cancer/National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC) definition and analyzed survival trends after diagnosis over 20 years. A data review committee evaluated 342 medical records that mentioned IA in the French Hospital Database on HIV. Validated cases were classified as fulfilling the EORTC criteria or otherwise as "HIV-related IA." Three periods were analyzed: pre-cART (before 1996), cART era prevoriconazole (1996-2001), and 2002-2011. Among 242 validated cases of IA, 124 (51%) fulfilled the EORTC criteria (EORTC-IA) and 118 (49%) were classified as "HIV-related," with similarly low CD4 cell counts in both groups. The proportion of EORTC-IA cases remained stable across the 3 periods (50%, 48%, and 54%, respectively). The 3-month survival rate improved after the advent of cART (38% vs 69%), with no difference between EORTC-IA and HIV-related IA (hazard ratio [HR], 1.2 95% confidence interval [CI] {0.7-1.8}). Voriconazole exposure decreased mortality in 2002-2011 (HR, 0.1 95% CI [0.01-0.8]). In the cART era, EORTC criteria, developed for use in hematology/oncology, still applied to only half the cases diagnosed among HIV-infected patients. A rapid diagnosis of IA is paramount to improve survival. For patients who do not fulfill the EORTC definition, we suggest that the addition of "HIV infected with a CD4 count <100 cells/µL" to the EORTC host criteria be validated. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions

  3. 78 FR 17888 - Periodic Review of Existing Regulations; Retrospective Review Under E.O. 13563

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-25

    ... Chapter V 48 CFR Chapter 28 Periodic Review of Existing Regulations; Retrospective Review Under E.O. 13563... issued Executive Order 13563, ``Improving Regulation and Regulatory Review,'' which sets forth principles and requirements designed to promote public participation, improve integration and innovation...

  4. MusaSAP1, a A20/AN1 zinc finger gene from banana functions as a positive regulator in different stress responses.

    PubMed

    Sreedharan, Shareena; Shekhawat, Upendra K Singh; Ganapathi, Thumballi R

    2012-11-01

    A20/AN1 zinc finger domain containing Stress Associated Proteins (SAP) are involved in diverse stress response pathways in plants. In the present study, a novel banana SAP gene, MusaSAP1, was identified from banana EST database and was subsequently characterized by overexpression in transgenic banana plants. Expression profiling in native banana plants showed that MusaSAP1 was up-regulated by drought, salt, cold, heat and oxidative stress as well as by treatment with abscisic acid. Cellular localization assay carried out by making a MusaSAP1::GFP fusion protein indicated that MusaSAP1 is incompletely translocated to nucleus. Copy number analysis performed using real time PCR and Southern blotting indicated that MusaSAP1 occurs in the banana genome in a single copy per 11 chromosome set. Transgenic banana plants constitutively overexpressing MusaSAP1 displayed better stress endurance characteristics as compared to controls in both in vitro and ex vivo assays. Lesser membrane damage as indicated by reduced malondialdehyde levels in transgenic leaves subjected to drought, salt or oxidative stress pointed towards significant role for MusaSAP1 in stress amelioration pathways of banana. Strong up-regulation of a polyphenol oxidase (PPO) coding transcript in MusaSAP1 overexpressing plants together with induction of MusaSAP1 by wounding and methyl jasmonate treatment indicated possible involvement of MusaSAP1 in biotic stress responses where PPOs perform major functions in multiple defense pathways.

  5. Urine cytology screening of French workers exposed to occupational urinary tract carcinogens: a prospective cohort study over a 20-year period.

    PubMed

    Dutheil, Frederic; Rouanet, Lucile; Mulliez, Aurélien; Naughton, Geraldine; Fontana, Luc; Druet-Cabanac, Michel; Moustafa, Farès; Chamoux, Alain

    2017-09-21

    To demonstrate that urine cytology screening can provide relevant epidemiological data for earlier detection of urothelial cancer caused by occupational exposure. Prospective cohort study. Industries using urothelial carcinogens in France. Urine samples were collected on site, after a work week and were analysed at the University Hospital of Clermont-Ferrand, France. Participants were workers exposed to urothelial carcinogens. Women and current smokers at time of study recruitment were exclusion criteria. Urine cells atypia were ranged into three classes: negative/normal, atypical/suspicious/dysplasia or positive/malignant. We included 2020 workers over a period of 20 years from 1993 to 2013: 606 worked in rubber manufacturing, 692 from metal processing, 245 in chemical industry and 477 in roadwork and building industry. Workers had a mean exposure of 15.2±10.4 years before their first urine cytology screening. There was a mean of 3.4±4.3 urine cytology screenings per worker between 1993 and 2013. 6478 cytology were normal, 462 suspicious and 13 malignant. Suspicious and malignant cytology occurred in 4.8% of workers exposed for 1-10 years, 6.2% for 11-20 years of exposure, 7.6% for 21-30 years and 8.6% for >30 years (p<0.001). Using exposure for 1-10 years as reference, the adjusted OR of receiving a suspicious or malignant diagnosis increased with duration of exposure: OR=1.50 (95% CI 1.10 to 2.05, p=0.01) for 21-30 years and OR=1.78 (95% CI 1.23 to 2.56, p=0.002) for >30 years of exposure. Using metal processing as reference, the risk of pathological urine cytology results increased for rubber manufacturing (OR=1.32, 95% CI 1.05 to 1.65, p=0.02), with a trend for roadwork and building industry (OR=1.39, 95% CI 0.98 to 1.97, p=0.07) and for chemical industry (OR=1.34, 95% CI 0.94 to 1.93, p=0.11). Urine cytology is a useful tool in occupational medicine. We promote new guidelines with an early screening of urothelial cancer by cytology, starting with

  6. Translational Regulation of the DOUBLETIME/CKIδ/ε Kinase by LARK Contributes to Circadian Period Modulation

    PubMed Central

    Huang, Yanmei; McNeil, Gerard P.; Jackson, F. Rob

    2014-01-01

    The Drosophila homolog of Casein Kinase I δ/ε, DOUBLETIME (DBT), is required for Wnt, Hedgehog, Fat and Hippo signaling as well as circadian clock function. Extensive studies have established a critical role of DBT in circadian period determination. However, how DBT expression is regulated remains largely unexplored. In this study, we show that translation of dbt transcripts are directly regulated by a rhythmic RNA-binding protein (RBP) called LARK (known as RBM4 in mammals). LARK promotes translation of specific alternative dbt transcripts in clock cells, in particular the dbt-RC transcript. Translation of dbt-RC exhibits circadian changes under free-running conditions, indicative of clock regulation. Translation of a newly identified transcript, dbt-RE, is induced by light in a LARK-dependent manner and oscillates under light/dark conditions. Altered LARK abundance affects circadian period length, and this phenotype can be modified by different dbt alleles. Increased LARK delays nuclear degradation of the PERIOD (PER) clock protein at the beginning of subjective day, consistent with the known role of DBT in PER dynamics. Taken together, these data support the idea that LARK influences circadian period and perhaps responses of the clock to light via the regulated translation of DBT. Our study is the first to investigate translational control of the DBT kinase, revealing its regulation by LARK and a novel role of this RBP in Drosophila circadian period modulation. PMID:25211129

  7. HMBA Enhances Prostratin-Induced Activation of Latent HIV-1 via Suppressing the Expression of Negative Feedback Regulator A20/TNFAIP3 in NF-κB Signaling

    PubMed Central

    Chen, Duchu; Wang, Huiping; Aweya, Jude Juventus; Chen, Yanheng; Chen, Meihua; Wu, Xiaomeng; Chen, Xiaonan; Lu, Jing

    2016-01-01

    In the past decade, much emphasis has been put on the transcriptional activation of HIV-1, which is proposed as a promised strategy for eradicating latent HIV-1 provirus. Two drugs, prostratin and hexamethylene bisacetamide (HMBA), have shown potent effects as inducers for releasing HIV-1 latency when used alone or in combination, although their cellular target(s) are currently not well understood, especially under drug combination. Here, we have shown that HMBA and prostratin synergistically release HIV-1 latency via different mechanisms. While prostratin strongly stimulates HMBA-induced HIV-1 transcription via improved P-TEFb activation, HMBA is capable of boosting NF-κB-dependent transcription initiation by suppressing prostratin-induced expression of the deubiquitinase A20, a negative feedback regulator in the NF-κB signaling pathway. In addition, HMBA was able to increase prostratin-induced phosphorylation and degradation of NF-κB inhibitor IκBα, thereby enhancing and prolonging prostratin-induced nuclear translocation of NF-κB, a prerequisite for stimulation of transcription initiation. Thus, by blocking the negative feedback circuit, HMBA functions as a signaling enhancer of the NF-κB signaling pathway. PMID:27529070

  8. BDNF regulates the maturation of inhibition and the critical period of plasticity in mouse visual cortex.

    PubMed

    Huang, Z J; Kirkwood, A; Pizzorusso, T; Porciatti, V; Morales, B; Bear, M F; Maffei, L; Tonegawa, S

    1999-09-17

    Maturation of the visual cortex is influenced by visual experience during an early postnatal period. The factors that regulate such a critical period remain unclear. We examined the maturation and plasticity of the visual cortex in transgenic mice in which the postnatal rise of brain-derived neurotrophic factor (BDNF) was accelerated. In these mice, the maturation of GABAergic innervation and inhibition was accelerated. Furthermore, the age-dependent decline of cortical long-term potentiation induced by white matter stimulation, a form of synaptic plasticity sensitive to cortical inhibition, occurred earlier. Finally, transgenic mice showed a precocious development of visual acuity and an earlier termination of the critical period for ocular dominance plasticity. We propose that BDNF promotes the maturation of cortical inhibition during early postnatal life, thereby regulating the critical period for visual cortical plasticity.

  9. Periodic retinoic acid–STRA8 signaling intersects with periodic germ-cell competencies to regulate spermatogenesis

    PubMed Central

    Endo, Tsutomu; Romer, Katherine A.; Anderson, Ericka L.; Baltus, Andrew E.; de Rooij, Dirk G.; Page, David C.

    2015-01-01

    Mammalian spermatogenesis—the transformation of stem cells into millions of haploid spermatozoa—is elaborately organized in time and space. We explored the underlying regulatory mechanisms by genetically and chemically perturbing spermatogenesis in vivo, focusing on spermatogonial differentiation, which begins a series of amplifying divisions, and meiotic initiation, which ends these divisions. We first found that, in mice lacking the retinoic acid (RA) target gene Stimulated by retinoic acid gene 8 (Stra8), undifferentiated spermatogonia accumulated in unusually high numbers as early as 10 d after birth, whereas differentiating spermatogonia were depleted. We thus conclude that Stra8, previously shown to be required for meiotic initiation, also promotes (but is not strictly required for) spermatogonial differentiation. Second, we found that injection of RA into wild-type adult males induced, independently, precocious spermatogonial differentiation and precocious meiotic initiation; thus, RA acts instructively on germ cells at both transitions. Third, the competencies of germ cells to undergo spermatogonial differentiation or meiotic initiation in response to RA were found to be distinct, periodic, and limited to particular seminiferous stages. Competencies for both transitions begin while RA levels are low, so that the germ cells respond as soon as RA levels rise. Together with other findings, our results demonstrate that periodic RA–STRA8 signaling intersects with periodic germ-cell competencies to regulate two distinct, cell-type-specific responses: spermatogonial differentiation and meiotic initiation. This simple mechanism, with one signal both starting and ending the amplifying divisions, contributes to the prodigious output of spermatozoa and to the elaborate organization of spermatogenesis. PMID:25902548

  10. Periodic retinoic acid-STRA8 signaling intersects with periodic germ-cell competencies to regulate spermatogenesis.

    PubMed

    Endo, Tsutomu; Romer, Katherine A; Anderson, Ericka L; Baltus, Andrew E; de Rooij, Dirk G; Page, David C

    2015-05-05

    Mammalian spermatogenesis--the transformation of stem cells into millions of haploid spermatozoa--is elaborately organized in time and space. We explored the underlying regulatory mechanisms by genetically and chemically perturbing spermatogenesis in vivo, focusing on spermatogonial differentiation, which begins a series of amplifying divisions, and meiotic initiation, which ends these divisions. We first found that, in mice lacking the retinoic acid (RA) target gene Stimulated by retinoic acid gene 8 (Stra8), undifferentiated spermatogonia accumulated in unusually high numbers as early as 10 d after birth, whereas differentiating spermatogonia were depleted. We thus conclude that Stra8, previously shown to be required for meiotic initiation, also promotes (but is not strictly required for) spermatogonial differentiation. Second, we found that injection of RA into wild-type adult males induced, independently, precocious spermatogonial differentiation and precocious meiotic initiation; thus, RA acts instructively on germ cells at both transitions. Third, the competencies of germ cells to undergo spermatogonial differentiation or meiotic initiation in response to RA were found to be distinct, periodic, and limited to particular seminiferous stages. Competencies for both transitions begin while RA levels are low, so that the germ cells respond as soon as RA levels rise. Together with other findings, our results demonstrate that periodic RA-STRA8 signaling intersects with periodic germ-cell competencies to regulate two distinct, cell-type-specific responses: spermatogonial differentiation and meiotic initiation. This simple mechanism, with one signal both starting and ending the amplifying divisions, contributes to the prodigious output of spermatozoa and to the elaborate organization of spermatogenesis.

  11. 76 FR 23520 - Periodic Review of Existing Regulations; Retrospective Review Under E.O. 13563

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-27

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Chapter I Periodic Review of Existing Regulations; Retrospective Review Under E.O. 13563 AGENCY: Food and Drug Administration, HHS. ACTION: Notification for... Regulatory Review,'' the Food and Drug Administration (FDA) is conducting a review of its...

  12. Molecular mechanisms that regulate the coupled period of the mammalian circadian clock.

    PubMed

    Kim, Jae Kyoung; Kilpatrick, Zachary P; Bennett, Matthew R; Josić, Krešimir

    2014-05-06

    In mammals, most cells in the brain and peripheral tissues generate circadian (∼24 h) rhythms autonomously. These self-sustained rhythms are coordinated and entrained by a master circadian clock in the suprachiasmatic nucleus (SCN). Within the SCN, the individual rhythms of each neuron are synchronized through intercellular signaling. One important feature of SCN is that the synchronized period is close to the population mean of cells' intrinsic periods. In this way, the synchronized period of the SCN stays close to the periods of cells in peripheral tissues. This is important because the SCN must entrain cells throughout the body. However, the mechanism that drives the period of the coupled SCN cells to the population mean is not known. We use mathematical modeling and analysis to show that the mechanism of transcription repression in the intracellular feedback loop plays a pivotal role in regulating the coupled period. Specifically, we use phase response curve analysis to show that the coupled period within the SCN stays near the population mean if transcriptional repression occurs via protein sequestration. In contrast, the coupled period is far from the mean if repression occurs through highly nonlinear Hill-type regulation (e.g., oligomer- or phosphorylation-based repression), as widely assumed in previous mathematical models. Furthermore, we find that the timescale of intercellular coupling needs to be fast compared to that of intracellular feedback to maintain the mean period. These findings reveal the important relationship between the intracellular transcriptional feedback loop and intercellular coupling. This relationship explains why transcriptional repression appears to occur via protein sequestration in multicellular organisms, mammals, and Drosophila, in contrast with the phosphorylation-based repression in unicellular organisms and syncytia. That is, transition to protein sequestration is essential for synchronizing multiple cells with a period

  13. Drosophila peptidyl-prolyl isomerase Pin1 modulates circadian rhythms via regulating levels of PERIOD.

    PubMed

    Kang, So Who; Lee, Euna; Cho, Eunjoo; Seo, Ji Hye; Ko, Hyuk Wan; Kim, Eun Young

    2015-07-31

    In animal circadian clock machinery, the phosphorylation program of PERIOD (PER) leads to the spatio-temporal regulation of diverse PER functions, which are crucial for the maintenance of ~24-hr circadian rhythmicity. The peptidyl-prolyl isomerase PIN1 modulates the diverse functions of its substrates by inducing conformational changes upon recognizing specific phosphorylated residues. Here, we show that overexpression of Drosophila pin1, dodo (dod), lengthens the locomotor behavioral period. Using Drosophila S2 cells, we demonstrate that Dod associates preferentially with phosphorylated species of PER, which delays the phosphorylation-dependent degradation of PER. Consistent with this, PER protein levels are higher in flies overexpressing dod. Taken together, we suggest that Dod plays a role in the maintenance of circadian period by regulating PER metabolism.

  14. Regulating Critical Period Plasticity: Insight from the Visual System to Fear Circuitry for Therapeutic Interventions

    PubMed Central

    Nabel, Elisa M.; Morishita, Hirofumi

    2013-01-01

    Early temporary windows of heightened brain plasticity called critical periods developmentally sculpt neural circuits and contribute to adult behavior. Regulatory mechanisms of visual cortex development – the preeminent model of experience-dependent critical period plasticity-actively limit adult plasticity and have proved fruitful therapeutic targets to reopen plasticity and rewire faulty visual system connections later in life. Interestingly, these molecular mechanisms have been implicated in the regulation of plasticity in other functions beyond vision. Applying mechanistic understandings of critical period plasticity in the visual cortex to fear circuitry may provide a conceptual framework for developing novel therapeutic tools to mitigate aberrant fear responses in post traumatic stress disorder. In this review, we turn to the model of experience-dependent visual plasticity to provide novel insights for the mechanisms regulating plasticity in the fear system. Fear circuitry, particularly fear memory erasure, also undergoes age-related changes in experience-dependent plasticity. We consider the contributions of molecular brakes that halt visual critical period plasticity to circuitry underlying fear memory erasure. A major molecular brake in the visual cortex, perineuronal net formation, recently has been identified in the development of fear systems that are resilient to fear memory erasure. The roles of other molecular brakes, myelin-related Nogo receptor signaling and Lynx family proteins – endogenous inhibitors for nicotinic acetylcholine receptor, are explored in the context of fear memory plasticity. Such fear plasticity regulators, including epigenetic effects, provide promising targets for therapeutic interventions. PMID:24273519

  15. Regulating critical period plasticity: insight from the visual system to fear circuitry for therapeutic interventions.

    PubMed

    Nabel, Elisa M; Morishita, Hirofumi

    2013-01-01

    Early temporary windows of heightened brain plasticity called critical periods developmentally sculpt neural circuits and contribute to adult behavior. Regulatory mechanisms of visual cortex development - the preeminent model of experience-dependent critical period plasticity-actively limit adult plasticity and have proved fruitful therapeutic targets to reopen plasticity and rewire faulty visual system connections later in life. Interestingly, these molecular mechanisms have been implicated in the regulation of plasticity in other functions beyond vision. Applying mechanistic understandings of critical period plasticity in the visual cortex to fear circuitry may provide a conceptual framework for developing novel therapeutic tools to mitigate aberrant fear responses in post traumatic stress disorder. In this review, we turn to the model of experience-dependent visual plasticity to provide novel insights for the mechanisms regulating plasticity in the fear system. Fear circuitry, particularly fear memory erasure, also undergoes age-related changes in experience-dependent plasticity. We consider the contributions of molecular brakes that halt visual critical period plasticity to circuitry underlying fear memory erasure. A major molecular brake in the visual cortex, perineuronal net formation, recently has been identified in the development of fear systems that are resilient to fear memory erasure. The roles of other molecular brakes, myelin-related Nogo receptor signaling and Lynx family proteins - endogenous inhibitors for nicotinic acetylcholine receptor, are explored in the context of fear memory plasticity. Such fear plasticity regulators, including epigenetic effects, provide promising targets for therapeutic interventions.

  16. Multiple circadian-regulated elements contribute to cycling period gene expression in Drosophila.

    PubMed Central

    Stanewsky, R; Jamison, C F; Plautz, J D; Kay, S A; Hall, J C

    1997-01-01

    A new regulatory element necessary for the correct temporal expression of the period (per) gene was identified by monitoring real-time per expression in living individual flies carrying two different period-luciferase transgenes. luciferase RNA driven from only the per promoter was not sufficient to replicate the normal pattern of per RNA cycling; however, a per-luc fusion RNA driven from a transgene containing additional per sequences cycled identically to endogenous per. The results indicate the existence of at least two circadian-regulated elements--one within the promoter and one within the transcribed portion of the per gene. Phase and amplitude analysis of both per-luc transgenes revealed that normal per expression requires the regulation of these elements at distinct phases and suggests a mechanism by which biological clocks sustain high-amplitude feedback oscillations. PMID:9305642

  17. Activity-dependent PSA expression regulates inhibitory maturation and onset of critical period plasticity.

    PubMed

    Di Cristo, Graziella; Chattopadhyaya, Bidisha; Kuhlman, Sandra J; Fu, Yu; Bélanger, Marie-Claude; Wu, Cai Zhi; Rutishauser, Urs; Maffei, Lamberto; Huang, Z Josh

    2007-12-01

    Functional maturation of GABAergic innervation in the developing visual cortex is regulated by neural activity and sensory inputs and in turn influences the critical period of ocular dominance plasticity. Here we show that polysialic acid (PSA), presented by the neural cell adhesion molecule, has a role in the maturation of GABAergic innervation and ocular dominance plasticity. Concentrations of PSA significantly decline shortly after eye opening in the adolescent mouse visual cortex; this decline is hindered by visual deprivation. The developmental and activity-dependent regulation of PSA expression is inversely correlated with the maturation of GABAergic innervation. Premature removal of PSA in visual cortex results in precocious maturation of perisomatic innervation by basket interneurons, enhanced inhibitory synaptic transmission, and earlier onset of ocular dominance plasticity. The developmental and activity-dependent decline of PSA expression therefore regulates the timing of the maturation of GABAergic inhibition and the onset of ocular dominance plasticity.

  18. Systems Chronobiology: Global Analysis of Gene Regulation in a 24-Hour Periodic World.

    PubMed

    Mermet, Jérôme; Yeung, Jake; Naef, Felix

    2017-03-01

    Mammals have evolved an internal timing system, the circadian clock, which synchronizes physiology and behavior to the daily light and dark cycles of the Earth. The master clock, located in the suprachiasmatic nucleus (SCN) of the brain, takes fluctuating light input from the retina and synchronizes other tissues to the same internal rhythm. The molecular clocks that drive these circadian rhythms are ticking in nearly all cells in the body. Efforts in systems chronobiology are now being directed at understanding, on a comprehensive scale, how the circadian clock controls different layers of gene regulation to provide robust timing cues at the cellular and tissue level. In this review, we introduce some basic concepts underlying periodicity of gene regulation, and then highlight recent genome-wide investigations on the propagation of rhythms across multiple regulatory layers in mammals, all the way from chromatin conformation to protein accumulation.

  19. The Period protein homolog LIN-42 negatively regulates microRNA biogenesis in C. elegans

    PubMed Central

    Van Wynsberghe, Priscilla M.; Finnegan, Emily F.; Stark, Thomas; Angelus, Evan P.; Homan, Kathryn E.; Yeo, Gene W.; Pasquinelli, Amy E.

    2014-01-01

    MicroRNAs (miRNAs) are small RNAs that post-transcriptionally regulate gene expression in many multicellular organisms. They are encoded in the genome and transcribed into primary (pri-) miRNAs before two processing steps that ultimately produce the mature miRNA. In order to generate the appropriate amount of a particular miRNA in the correct location at the correct time, proper regulation of miRNA biogenesis is essential. Here we identify the Period protein homolog LIN-42 as a new regulator of miRNA biogenesis in Caenorhabditis elegans. We mapped a spontaneous suppressor of the normally lethal let-7(n2853) allele to the lin-42 gene. Mutations in this allele (ap201) or a second lin-42 allele (n1089) caused increased mature let-7 miRNA levels at most time points when mature let-7 miRNA is normally expressed. Levels of pri-let-7 and a let-7 transcriptional reporter were also increased in lin-42(n1089) worms. These results indicate that LIN-42 normally represses pri-let-7 transcription and thus the accumulation of let-7 miRNA. This inhibition is not specific to let-7, as pri- and mature levels of lin-4 and miR-35 were also increased in lin-42 mutants. Furthermore, small RNA-seq analysis showed widespread increases in the levels of mature miRNAs in lin-42 mutants. Thus, we propose that the period protein homolog LIN-42 is a global regulator of miRNA biogenesis. PMID:24699545

  20. The Period protein homolog LIN-42 negatively regulates microRNA biogenesis in C. elegans.

    PubMed

    Van Wynsberghe, Priscilla M; Finnegan, Emily F; Stark, Thomas; Angelus, Evan P; Homan, Kathryn E; Yeo, Gene W; Pasquinelli, Amy E

    2014-06-15

    MicroRNAs (miRNAs) are small RNAs that post-transcriptionally regulate gene expression in many multicellular organisms. They are encoded in the genome and transcribed into primary (pri-) miRNAs before two processing steps that ultimately produce the mature miRNA. In order to generate the appropriate amount of a particular miRNA in the correct location at the correct time, proper regulation of miRNA biogenesis is essential. Here we identify the Period protein homolog LIN-42 as a new regulator of miRNA biogenesis in Caenorhabditis elegans. We mapped a spontaneous suppressor of the normally lethal let-7(n2853) allele to the lin-42 gene. Mutations in this allele (ap201) or a second lin-42 allele (n1089) caused increased mature let-7 miRNA levels at most time points when mature let-7 miRNA is normally expressed. Levels of pri-let-7 and a let-7 transcriptional reporter were also increased in lin-42(n1089) worms. These results indicate that LIN-42 normally represses pri-let-7 transcription and thus the accumulation of let-7 miRNA. This inhibition is not specific to let-7, as pri- and mature levels of lin-4 and miR-35 were also increased in lin-42 mutants. Furthermore, small RNA-seq analysis showed widespread increases in the levels of mature miRNAs in lin-42 mutants. Thus, we propose that the period protein homolog LIN-42 is a global regulator of miRNA biogenesis.

  1. Period-regulated feeding behavior and TOR signaling modulate survival of infection

    PubMed Central

    Allen, Victoria W.; O’Connor, Reed M.; Ulgherait, Matt; Zhou, Clarice G.; Stone, Elizabeth F.; Hill, Vanessa M.; Murphy, Keith R.; Canman, Julie C.; Ja, William W.; Shirasu-Hiza, Mimi M.

    2015-01-01

    SUMMARY Most metazoans undergo dynamic, circadian-regulated changes in behavior and physiology. Currently it is unknown how circadian-regulated behavior impacts immunity against infection. Two broad categories of defense against bacterial infection are resistance, control of microbial growth, and tolerance, control of the pathogenic effects of infection. Our study of behaviorally arrhythmic Drosophila circadian Period mutants identified a novel link between nutrient intake and tolerance of infection with B. cepacia, a bacterial pathogen of rising importance in hospital-acquired infections. We found that infection tolerance in wild-type animals is stimulated by acute exposure to dietary glucose and amino acids. Glucose-stimulated tolerance was induced by feeding or direct injection; injections revealed a narrow window for glucose-stimulated tolerance. In contrast, amino acids stimulated tolerance only when ingested. We investigated the role of a known amino acid-sensing pathway, the TOR (Target of Rapamycin) pathway, in immunity. TORC1 is circadian-regulated and inhibition of TORC1 decreased resistance, as in vertebrates. Surprisingly, inhibition of the less well-characterized TOR complex 2 (TORC2) dramatically increased survival, through both resistance and tolerance mechanisms. This work suggests that dietary intake on the day of infection by B. cepacia can make a significant difference in long-term survival. We further demonstrate that TOR signaling mediates both resistance and tolerance of infection and identify TORC2 as a novel potential therapeutic target for increasing survival of infection. PMID:26748856

  2. LIN-42, the Caenorhabditis elegans PERIOD homolog, Negatively Regulates MicroRNA Transcription

    PubMed Central

    Aguirre-Chen, Cristina; Hammell, Christopher M.

    2014-01-01

    During C. elegans development, microRNAs (miRNAs) function as molecular switches that define temporal gene expression and cell lineage patterns in a dosage-dependent manner. It is critical, therefore, that the expression of miRNAs be tightly regulated so that target mRNA expression is properly controlled. The molecular mechanisms that function to optimize or control miRNA levels during development are unknown. Here we find that mutations in lin-42, the C. elegans homolog of the circadian-related period gene, suppress multiple dosage-dependent miRNA phenotypes including those involved in developmental timing and neuronal cell fate determination. Analysis of mature miRNA levels in lin-42 mutants indicates that lin-42 functions to attenuate miRNA expression. Through the analysis of transcriptional reporters, we show that the upstream cis-acting regulatory regions of several miRNA genes are sufficient to promote highly dynamic transcription that is coupled to the molting cycles of post-embryonic development. Immunoprecipitation of LIN-42 complexes indicates that LIN-42 binds the putative cis-regulatory regions of both non-coding and protein-coding genes and likely plays a role in regulating their transcription. Consistent with this hypothesis, analysis of miRNA transcriptional reporters in lin-42 mutants indicates that lin-42 regulates miRNA transcription. Surprisingly, strong loss-of-function mutations in lin-42 do not abolish the oscillatory expression patterns of lin-4 and let-7 transcription but lead to increased expression of these genes. We propose that lin-42 functions to negatively regulate the transcriptional output of multiple miRNAs and mRNAs and therefore coordinates the expression levels of genes that dictate temporal cell fate with other regulatory programs that promote rhythmic gene expression. PMID:25032706

  3. Caenorhabditis elegans period homolog lin-42 regulates the timing of heterochronic miRNA expression.

    PubMed

    McCulloch, Katherine A; Rougvie, Ann E

    2014-10-28

    MicroRNAs (miRNAs) are small RNAs that regulate gene expression posttranscriptionally via the 3' UTR of target mRNAs and were first identified in the Caenorhabditis elegans heterochronic pathway. miRNAs have since been found in many organisms and have broad functions, including control of differentiation and pluripotency in humans. lin-4 and let-7-family miRNAs regulate developmental timing in C. elegans, and their proper temporal expression ensures cell lineage patterns are correctly timed and sequentially executed. Although much is known about miRNA biogenesis, less is understood about how miRNA expression is timed and regulated. lin-42, the worm homolog of the circadian rhythm gene period of flies and mammals, is another core component of the heterochronic gene pathway. lin-42 mutants have a precocious phenotype, in which later-stage programs are executed too early, but the placement of lin-42 in the timing pathway is unclear. Here, we demonstrate that lin-42 negatively regulates heterochronic miRNA transcription. let-7 and the related miRNA miR-48 accumulate precociously in lin-42 mutants. This defect reflects transcriptional misregulation because enhanced expression of both primary miRNA transcripts (pri-miRNAs) and a let-7 promoter::gfp fusion are observed. The pri-miRNA levels oscillate during larval development, in a pattern reminiscent of lin-42 expression. Importantly, we show that lin-42 is not required for this cycling; instead, peak amplitude is increased. Genetic analyses further confirm that lin-42 acts through let-7 family miRNAs. Taken together, these data show that a key function of lin-42 in developmental timing is to dampen pri-miRNAs levels, preventing their premature expression as mature miRNAs.

  4. LIN-42, the Caenorhabditis elegans PERIOD homolog, negatively regulates microRNA transcription.

    PubMed

    Perales, Roberto; King, Dana M; Aguirre-Chen, Cristina; Hammell, Christopher M

    2014-07-01

    During C. elegans development, microRNAs (miRNAs) function as molecular switches that define temporal gene expression and cell lineage patterns in a dosage-dependent manner. It is critical, therefore, that the expression of miRNAs be tightly regulated so that target mRNA expression is properly controlled. The molecular mechanisms that function to optimize or control miRNA levels during development are unknown. Here we find that mutations in lin-42, the C. elegans homolog of the circadian-related period gene, suppress multiple dosage-dependent miRNA phenotypes including those involved in developmental timing and neuronal cell fate determination. Analysis of mature miRNA levels in lin-42 mutants indicates that lin-42 functions to attenuate miRNA expression. Through the analysis of transcriptional reporters, we show that the upstream cis-acting regulatory regions of several miRNA genes are sufficient to promote highly dynamic transcription that is coupled to the molting cycles of post-embryonic development. Immunoprecipitation of LIN-42 complexes indicates that LIN-42 binds the putative cis-regulatory regions of both non-coding and protein-coding genes and likely plays a role in regulating their transcription. Consistent with this hypothesis, analysis of miRNA transcriptional reporters in lin-42 mutants indicates that lin-42 regulates miRNA transcription. Surprisingly, strong loss-of-function mutations in lin-42 do not abolish the oscillatory expression patterns of lin-4 and let-7 transcription but lead to increased expression of these genes. We propose that lin-42 functions to negatively regulate the transcriptional output of multiple miRNAs and mRNAs and therefore coordinates the expression levels of genes that dictate temporal cell fate with other regulatory programs that promote rhythmic gene expression.

  5. Circadian oscillations in period gene mRNA levels are transcriptionally regulated.

    PubMed Central

    Hardin, P E; Hall, J C; Rosbash, M

    1992-01-01

    The period (per) gene is involved in regulating circadian rhythms in Drosophila melanogaster. The per gene is expressed in a circadian manner, where fluctuations in per mRNA abundance are influenced by its own translation product, which also cycles in abundance. Since per gene expression is necessary for circadian rhythmicity, we sought to determine how certain features of this feedback loop operate. The results of this study reveal that fluctuations in per mRNA are primarily controlled by fluctuations in per gene transcription, that per mRNA has a relatively short half-life, and that sequences sufficient to drive per mRNA cycling are present in 1.3 kilobases of 5' flanking sequences. These and other results indicate that the per feedback loop has all of the basic properties necessary to be a component of a circadian oscillator. Images PMID:1465387

  6. Differential expression and regulation of Cryab in mouse uterus during preimplantation period.

    PubMed

    Tian, Xue-Chao; Wang, Qu-Yuan; Li, Dang-Dang; Wang, Shou-Tang; Yang, Zhan-Qing; Guo, Bin; Yue, Zhan-Peng

    2013-06-01

    The aim of this study was to examine the expression and regulation of the crystallin, alpha B (Cryab) gene in mouse uterus during the peri-implantation period by in situ hybridization and real-time PCR. There was no detectable Cryab mRNA signal on days 1-4 of pregnancy. On day 5 of pregnancy when embryo implanted, a high level of Cryab mRNA signal was found in the subluminal stroma surrounding the implanting blastocyst. On days 6-8, Cryab mRNA was strongly expressed in the primary decidua. By real-time PCR, a high level of Cryab expression was detected on days 7 and 8 of pregnancy, although Cryab expression was seen from days 1 to 8. Under in vivo and in vitro artificial decidualization, Cryab expression was significantly elevated. Compared with the progesterone-primed delayed implantation uterus, a high level of Cryab mRNA expression was observed in estrogen-activated implantation uterus. In the uterine stromal cells, cAMP, estrogen, and progesterone could induce the expression of Cryab gene. In the ovariectomized mouse uterus, estrogen could also induce the expression of Cryab while progesterone inhibited its expression. Our data suggest that Cryab may play an important role during mouse embryo implantation and decidualization and that estrogen and progesterone can regulate the expression of Cryab gene.

  7. Basigin expression and hormonal regulation in mouse uterus during the peri-implantation period.

    PubMed

    Xiao, Li-Juan; Chang, Hong; Ding, Nai-Zheng; Ni, Hua; Kadomatsu, Kenji; Yang, Zeng-Ming

    2002-09-01

    Basigin, a transmembrane glycoprotein belonging to the immunoglobulin superfamily, has been shown to be essential for fertilization and implantation. The aim of this study was to determine the expression and hormonal regulation of basigin gene in mouse uterus during the peri-implantation period. Basigin immunostaining and mRNA were strongly localized in luminal and glandular epithelium on day 1 of pregnancy and gradually decreased to a basal level from day 2-4 of pregnancy. Basigin mRNA expression in the sub-luminal stroma was first detected on day 3 of pregnancy and increased on day 4 of pregnancy. On day 5 of pregnancy, the expression of basigin protein and mRNA was only detected in the implanting embryos, and the luminal epithelium and sub-luminal stroma surrounding the embryos. A similar expression pattern of basigin was also induced in the delayed-implantation uterus which was activated by estrogen injection. On day 6-8 of pregnancy, although a basal level of basigin protein was detected in the secondary decidual zone, basigin mRNA expression was strongly seen in this location. Basigin mRNA was also highly expressed in the decidualized cells under artificial decidualization. Estrogen significantly stimulated basigin expression in the ovariectomized mouse uterus. A high level of basigin immunostaining and mRNA was also seen in proestrus and estrus uteri. These results suggest that basigin expression is closely related to mouse implantation and up-regulated by estrogen.

  8. The hypersensitive glucocorticoid response specifically regulates period 1 and expression of circadian genes.

    PubMed

    Reddy, Timothy E; Gertz, Jason; Crawford, Gregory E; Garabedian, Michael J; Myers, Richard M

    2012-09-01

    Glucocorticoids regulate gene expression by binding and activating the glucocorticoid receptor (GR). While ligand affinity determines the global sensitivity of the response, additional proteins act on the genome to tune sensitivity of some genes. However, the genomic extent and specificity of dose-specific glucocorticoid responses are unknown. We show that dose-specific glucocorticoid responses are extraordinarily specific at the genomic scale, able to distinctly express a single gene, the circadian rhythm gene for Period 1 (PER1), at concentrations consistent with the nighttime nadir of human cortisol. We mapped the PER1 response to a single GR binding site. The specific GR binding sequence did not impact sensitivity, and we instead attributed the response to a combination of additional transcription factors and chromatin accessibility acting in the same locus. The PER1 hypersensitive response element is conserved in the mouse, where we found similar upregulation of Per1 in pituitary cells. Targeted and transient overexpression of PER1 led to regulation of additional circadian rhythm genes hours later, suggesting that hypersensitive expression of PER1 impacts circadian gene expression. These findings show that hypersensitive GR binding occurs throughout the genome, drives targeted gene expression, and may be important to endocrine mediation of peripheral circadian rhythms.

  9. Differential expression and regulation of Runx1 in mouse uterus during the peri-implantation period.

    PubMed

    Bai, Zhi-Kun; Li, Dang-Dang; Guo, Chuan-Hui; Yang, Zhan-Qing; Cao, Hang; Guo, Bin; Yue, Zhan-Peng

    2015-10-01

    Runx1 transcription factor is a key developmental regulator. However, little is known about the effects of Runx1 on embryo implantation and decidualization. The aim of this study is to examine the expression and regulation of Runx1 in mouse uterus during the peri-implantation period. There was no evident Runx1 mRNA signal on days 1-4 of pregnancy. On day 5 of pregnancy, Runx1 mRNA was mainly localized in the subluminal stroma surrounding the implanting blastocyst. A similar result was observed in the estrogen-activated implantation uterus. Simultaneously, a high level of Runx1 mRNA expression was detected on days 6-8 of pregnancy and under artificial decidualization. 8-Br-cAMP could induce the expression of Runx1 mRNA in the uterine stromal cells. Moreover, the induction was obviously blocked by PKA inhibitor H89. Inhibition of Runx1 with specific siRNA could decrease the proliferation of stromal cells and expression of decidual markers Prl8a2 and Prl3c1 in the uterine stromal cells. Further study found that inhibition of Runx1 could also suppress the expression of Cox-2, mPGES-1 and Mmp2 genes in uterine stromal cells. Estrogen and progesterone could induce the expression of Runx1 mRNA in ovariectomized mouse uterus and uterine stromal cells. Taken together, these data suggest that Runx1 may play an important role during mouse decidualization.

  10. period-Regulated Feeding Behavior and TOR Signaling Modulate Survival of Infection.

    PubMed

    Allen, Victoria W; O'Connor, Reed M; Ulgherait, Matthew; Zhou, Clarice G; Stone, Elizabeth F; Hill, Vanessa M; Murphy, Keith R; Canman, Julie C; Ja, William W; Shirasu-Hiza, Mimi M

    2016-01-25

    Most metazoans undergo dynamic, circadian-regulated changes in behavior and physiology. Currently, it is unknown how circadian-regulated behavior impacts immunity against infection. Two broad categories of defense against bacterial infection are resistance, control of microbial growth, and tolerance, control of the pathogenic effects of infection. Our study of behaviorally arrhythmic Drosophila circadian period mutants identified a novel link between nutrient intake and tolerance of infection with B. cepacia, a bacterial pathogen of rising importance in hospital-acquired infections. We found that infection tolerance in wild-type animals is stimulated by acute exposure to dietary glucose and amino acids. Glucose-stimulated tolerance was induced by feeding or direct injection; injections revealed a narrow window for glucose-stimulated tolerance. In contrast, amino acids stimulated tolerance only when ingested. We investigated the role of a known amino-acid-sensing pathway, the TOR (Target of Rapamycin) pathway, in immunity. TORC1 is circadian regulated and inhibition of TORC1 decreased resistance, as in vertebrates. Surprisingly, inhibition of the less well-characterized TOR complex 2 (TORC2) dramatically increased survival, through both resistance and tolerance mechanisms. This work suggests that dietary intake on the day of infection by B. cepacia can make a significant difference in long-term survival. We further demonstrate that TOR signaling mediates both resistance and tolerance of infection and identify TORC2 as a novel potential therapeutic target for increasing survival of infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Rapid down-regulation of mammalian Period genes during behavioral resetting of the circadian clock

    PubMed Central

    Maywood, E. S.; Mrosovsky, N.; Field, M. D.; Hastings, M. H.

    1999-01-01

    The pervasive role of circadian clocks in regulating physiology and behavior is widely recognized. Their adaptive value is their ability to be entrained by environmental cues such that the internal circadian phase is a reliable predictor of solar time. In mammals, both light and nonphotic behavioral cues can entrain the principal oscillator of the hypothalamic suprachiasmatic nuclei (SCN). However, although light can advance or delay the clock during circadian night, behavioral events trigger phase advances during the subjective day, when the clock is insensitive to light. The recent identification of Period (Per) genes in mammals, homologues of dperiod, which encodes a core element of the circadian clockwork in Drosophila, now provides the opportunity to explain circadian timing and entrainment at a molecular level. In mice, expression of mPer1 and mPer2 in the SCN is rhythmic and acutely up-regulated by light. Moreover, the temporal relations between mRNA and protein cycles are consistent with a clock based on a transcriptional/translational feedback loop. Here we describe circadian oscillations of Per1 and Per2 in the SCN of the Syrian hamster, showing that PER1 protein and mRNA cycles again behave in a manner consistent with a negative-feedback oscillator. Furthermore, we demonstrate that nonphotic resetting has the opposite effect to light: acutely down-regulating these genes. Their sensitivity to nonphotic resetting cues supports their proposed role as core elements of the circadian oscillator. Moreover, this study provides an explanation at the molecular level for the contrasting but convergent effects of photic and nonphotic cues on the clock. PMID:10611364

  12. Experimental validation of advanced regulations for superconducting magnet cooling undergoing periodic heat loads

    NASA Astrophysics Data System (ADS)

    Lagier, B.; Rousset, B.; Hoa, C.; Bonnay, P.

    2014-01-01

    Superconducting magnets used in tokamaks undergo periodic heat load caused by cycling plasma operations inducing AC losses, neutrons fluxes and eddy currents in magnet structures. In the cryogenic system of JT60-SA tokamak, the Auxiliary Cold Box (ACB) distributes helium from the refrigerator to the cryogenic users and in particular to the superconducting magnets. ACB comprises a saturated helium bath with immersed heat exchangers, extracting heat from independent cooling loops. The supercritical helium flow in each cooling loop is driven by a cold circulator. In order to safely operate the refrigerator during plasma pulses, the interface between the ACB and the refrigerator shall be as stable as possible, with well-balanced bath inlet and outlet mass flows during cycling operation. The solution presented in this paper relies on a combination of regulations to smooth pulsed heat loads and to keep a constant refrigeration power during all the cycle. Two smoothing strategies are presented, both regulating the outlet mass flow of the bath: the first one using the bath as a thermal buffer and the second one storing energy in the loop by varying the cold circulator speed. The bath outlet mass flow is also controlled by an immersed resistive heater which enables a constant evaporation rate in the bath when power coming from the loops is decreasing. The refrigeration power is controlled so that the compensating power remains within an acceptable margin. Experimental validation is achieved using the HELIOS facility. This facility running at CEA Grenoble since 2010 is a scaled down model of the ACB bath and Central Solenoid magnet cooling loop of the JT60-SA tokamak. Test results show performances and robustness of the regulations.

  13. Experimental validation of advanced regulations for superconducting magnet cooling undergoing periodic heat loads

    SciTech Connect

    Lagier, B.; Rousset, B.; Hoa, C.; Bonnay, P.

    2014-01-29

    Superconducting magnets used in tokamaks undergo periodic heat load caused by cycling plasma operations inducing AC losses, neutrons fluxes and eddy currents in magnet structures. In the cryogenic system of JT60-SA tokamak, the Auxiliary Cold Box (ACB) distributes helium from the refrigerator to the cryogenic users and in particular to the superconducting magnets. ACB comprises a saturated helium bath with immersed heat exchangers, extracting heat from independent cooling loops. The supercritical helium flow in each cooling loop is driven by a cold circulator. In order to safely operate the refrigerator during plasma pulses, the interface between the ACB and the refrigerator shall be as stable as possible, with well-balanced bath inlet and outlet mass flows during cycling operation. The solution presented in this paper relies on a combination of regulations to smooth pulsed heat loads and to keep a constant refrigeration power during all the cycle. Two smoothing strategies are presented, both regulating the outlet mass flow of the bath: the first one using the bath as a thermal buffer and the second one storing energy in the loop by varying the cold circulator speed. The bath outlet mass flow is also controlled by an immersed resistive heater which enables a constant evaporation rate in the bath when power coming from the loops is decreasing. The refrigeration power is controlled so that the compensating power remains within an acceptable margin. Experimental validation is achieved using the HELIOS facility. This facility running at CEA Grenoble since 2010 is a scaled down model of the ACB bath and Central Solenoid magnet cooling loop of the JT60-SA tokamak. Test results show performances and robustness of the regulations.

  14. Fan-Shaped Body Neurons Are Involved in "Period"-Dependent Regulation of Long-Term Courtship Memory in "Drosophila"

    ERIC Educational Resources Information Center

    Sakai, Takaomi; Inami, Show; Sato, Shoma; Kitamoto, Toshihiro

    2012-01-01

    In addition to its established function in the regulation of circadian rhythms, the "Drosophila" gene "period" ("per") also plays an important role in processing long-term memory (LTM). Here, we used courtship conditioning as a learning paradigm and revealed that (1) overexpression and knocking down of "per" in subsets of brain neurons enhance and…

  15. Fan-Shaped Body Neurons Are Involved in "Period"-Dependent Regulation of Long-Term Courtship Memory in "Drosophila"

    ERIC Educational Resources Information Center

    Sakai, Takaomi; Inami, Show; Sato, Shoma; Kitamoto, Toshihiro

    2012-01-01

    In addition to its established function in the regulation of circadian rhythms, the "Drosophila" gene "period" ("per") also plays an important role in processing long-term memory (LTM). Here, we used courtship conditioning as a learning paradigm and revealed that (1) overexpression and knocking down of "per" in subsets of brain neurons enhance and…

  16. [Regulation of behavior in the period between the world wars: Robert Musil and Kurt Lewin].

    PubMed

    Innerhofer, Roland; Rothe, Katja

    2010-12-01

    The paper attempts to reconstruct the proto-cybernetic concept of regulation which emerged in early 20th century both in biology and psychology, and was critically reflected in literature. The basic premise is that Kurt Lewin's field-theoretical psychology played a crucial role in the development of behavioral self-regulation concepts. The goal is to show (1) that Lewin's early experiments and theories were based on the idea of a dynamic process of self-regulation determined by the actors and their personal motivation and interaction, (2) that this concept of self-regulation functioned as a camouflage for power-strategies that aimed to regulate and optimize the economic production and social reproduction processes, (3) that in Robert Musil's fragmentary, 'fringing' novel The Man without Qualities the attempt to optimize the social and economic behavior and to establish a homeostatic state proved to be a complete failure. As a notable result, this 'literary test' of behavioral self-regulation revealed the violence and imbalance of power inherent in this concept of self-regulation and its practical implementation.

  17. Sensitive Periods of Emotion Regulation: Influences of Parental Care on Frontoamygdala Circuitry and Plasticity

    ERIC Educational Resources Information Center

    Gee, Dylan G.

    2016-01-01

    Early caregiving experiences play a central role in shaping emotional development, stress physiology, and refinement of limbic circuitry. Converging evidence across species delineates a sensitive period of heightened neuroplasticity when frontoamygdala circuitry is especially amenable to caregiver inputs early in life. During this period, parental…

  18. Sensitive Periods of Emotion Regulation: Influences of Parental Care on Frontoamygdala Circuitry and Plasticity

    ERIC Educational Resources Information Center

    Gee, Dylan G.

    2016-01-01

    Early caregiving experiences play a central role in shaping emotional development, stress physiology, and refinement of limbic circuitry. Converging evidence across species delineates a sensitive period of heightened neuroplasticity when frontoamygdala circuitry is especially amenable to caregiver inputs early in life. During this period, parental…

  19. 76 FR 13088 - Seaway Regulations and Rules: Periodic Update, Various Categories

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-10

    ... materials transportation, Navigation (water), Penalties, Radio, Reporting and recordkeeping requirements... TRANSPORTATION Saint Lawrence Seaway Development Corporation 33 CFR Part 401 RIN 2135-AA29 Seaway Regulations and... Order 12866 does not apply and evaluation under the Department of Transportation's Regulatory...

  20. The Jumonji C domain-containing protein JMJ30 regulates period length in the Arabidopsis circadian clock.

    PubMed

    Lu, Sheen X; Knowles, Stephen M; Webb, Candace J; Celaya, R Brandon; Cha, Chuah; Siu, Jonathan P; Tobin, Elaine M

    2011-02-01

    Histone methylation plays an essential role in regulating chromatin structure and gene expression. Jumonji C (JmjC) domain-containing proteins are generally known as histone demethylases. Circadian clocks regulate a large number of biological processes, and recent studies suggest that chromatin remodeling has evolved as an important mechanism for regulating both plant and mammalian circadian systems. Here, we analyzed a subgroup of JmjC domain-containing proteins and identified Arabidopsis (Arabidopsis thaliana) JMJ30 as a novel clock component involved in controlling the circadian period. Analysis of loss- and gain-of-function mutants of JMJ30 indicates that this evening-expressed gene is a genetic regulator of period length in the Arabidopsis circadian clock. Furthermore, two key components of the central oscillator of plants, transcription factors CIRCADIAN CLOCK ASSOCIATED1 and LATE ELONGATED HYPOCOTYL, bind directly to the JMJ30 promoter to repress its expression, suggesting that JMJ30 regulates the pace of the circadian clock in close association with the central oscillator. JMJ30 represents, to our knowledge, the first JmjC domain-containing protein involved in circadian function, and we envision that this provides a possible molecular connection between chromatin remodeling and the circadian clock.

  1. Neuregulin-Dependent Regulation of Fast-Spiking Interneuron Excitability Controls the Timing of the Critical Period.

    PubMed

    Gu, Yu; Tran, Trinh; Murase, Sachiko; Borrell, Andrew; Kirkwood, Alfredo; Quinlan, Elizabeth M

    2016-10-05

    Maturation of excitatory drive onto fast-spiking interneurons (FS INs) in the visual cortex has been implicated in the control of the timing of the critical period for ocular dominance plasticity. However, the mechanisms that regulate the strength of these synapses over cortical development are not understood. Here we use a mouse model to show that neuregulin (NRG) and the receptor tyrosine kinase erbB4 regulate the timing of the critical period. NRG1 enhanced the strength of excitatory synapses onto FS INs, which inhibited ocular dominance plasticity during the critical period but rescued plasticity in transgenics with hypoexcitable FS INs. Blocking the effects of endogenous neuregulin via inhibition of erbBs rescued ocular dominance plasticity in postcritical period adults, allowing recovery from amblyopia induced by chronic monocular deprivation. Thus, the strength of excitation onto FS INs is a key determinant of critical period plasticity and is maintained at high levels by NRG-erbB4 signaling to constrain plasticity in adulthood.

  2. Zinc Oxide Nanoparticles Suppress LPS-Induced NF-κB Activation by Inducing A20, a Negative Regulator of NF-κB, in RAW 264.7 Macrophages.

    PubMed

    Kim, Min-Ho; Jeong, Hyun-Ja

    2015-09-01

    Zinc contained in solar salt and bamboo salt plays a critical role in various immune responses. Zinc oxide is a source of zinc, and recently it has been reported that zinc oxide nanoparticles (ZO-NP) more effectively decrease allergic inflammatory reactions than zinc oxide bulk material. The aim of this work was to investigate the regulatory effect of ZO-NP on interferon (IFN)-γ plus lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. ZO-NP (0.1-10 μg/mL) did not affect cell viability but toxicity was evident at a ZO-NP concentration of 100 μg/mL. ZO-NP (10 μg/mL) inhibited the IFN-γ plus LPS-induced production of nitric oxide and the protein expressions of inducible nitric oxide synthase and cyclooxygenase-2. The productions of inflammatory cytokines, such as, interleukin (IL)-1β and tumor necrosis factor (TNF)-α were increased by IFN-γ plus LPS but down-regulated by ZO-NP treatment. Furthermore, the up-regulations of IL-1β and TNF-α mRNAs by IFN-γ plus LPS were reduced by ZO-NP at low (0.1 μg/mL) and high (10 μg/mL) concentrations. ZO-NP (0.1, 1, and 10 μg/mL) inhibited the nuclear translocation of nuclear factor-κB by blocking IκBα phosphorylation and degradation. In addition, ZO-NP induced the expression of A20, a zinc finger protein and negative regulator of NF-κB. In conclusion, the present study demonstrated that ZO-NP offer a potential means of treating inflammatory diseases.

  3. 76 FR 5104 - Seaway Regulations and Rules: Periodic Update, Various Categories

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-28

    ... Management and Budget review. List of Subjects in 33 CFR Part 401 Hazardous materials transportation.... Mail: Docket Management Facility; U.S. Department of Transportation, 1200 New Jersey Avenue, SE., West....Regulations.gov ; or in person at the Docket Management Facility; U.S. Department of Transportation,...

  4. MULTIPLE STABLE PERIODIC SOLUTIONS IN A MODEL FOR THE HORMONAL REGULATION OF THE MENSTRUAL CYCLE

    EPA Science Inventory

    ABSTRACT

    The pituitary hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and the ovarian hormones, estradiol (E2), progesterone (P4), and inhibin (Ih), are five hormones important for the regulation and maintenance of the human menstrual cycle. The...

  5. MULTIPLE STABLE PERIODIC SOLUTIONS IN A MODEL FOR THE HORMONAL REGULATION OF THE MENSTRUAL CYCLE

    EPA Science Inventory

    ABSTRACT

    The pituitary hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and the ovarian hormones, estradiol (E2), progesterone (P4), and inhibin (Ih), are five hormones important for the regulation and maintenance of the human menstrual cycle. The...

  6. Identification of cell cycle-regulated genes periodically expressed in U2OS cells and their regulation by FOXM1 and E2F transcription factors.

    PubMed

    Grant, Gavin D; Brooks, Lionel; Zhang, Xiaoyang; Mahoney, J Matthew; Martyanov, Viktor; Wood, Tammara A; Sherlock, Gavin; Cheng, Chao; Whitfield, Michael L

    2013-12-01

    We identify the cell cycle-regulated mRNA transcripts genome-wide in the osteosarcoma-derived U2OS cell line. This results in 2140 transcripts mapping to 1871 unique cell cycle-regulated genes that show periodic oscillations across multiple synchronous cell cycles. We identify genomic loci bound by the G2/M transcription factor FOXM1 by chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) and associate these with cell cycle-regulated genes. FOXM1 is bound to cell cycle-regulated genes with peak expression in both S phase and G2/M phases. We show that ChIP-seq genomic loci are responsive to FOXM1 using a real-time luciferase assay in live cells, showing that FOXM1 strongly activates promoters of G2/M phase genes and weakly activates those induced in S phase. Analysis of ChIP-seq data from a panel of cell cycle transcription factors (E2F1, E2F4, E2F6, and GABPA) from the Encyclopedia of DNA Elements and ChIP-seq data for the DREAM complex finds that a set of core cell cycle genes regulated in both U2OS and HeLa cells are bound by multiple cell cycle transcription factors. These data identify the cell cycle-regulated genes in a second cancer-derived cell line and provide a comprehensive picture of the transcriptional regulatory systems controlling periodic gene expression in the human cell division cycle.

  7. Identification of cell cycle–regulated genes periodically expressed in U2OS cells and their regulation by FOXM1 and E2F transcription factors

    PubMed Central

    Grant, Gavin D.; Brooks, Lionel; Zhang, Xiaoyang; Mahoney, J. Matthew; Martyanov, Viktor; Wood, Tammara A.; Sherlock, Gavin; Cheng, Chao; Whitfield, Michael L.

    2013-01-01

    We identify the cell cycle–regulated mRNA transcripts genome-wide in the osteosarcoma-derived U2OS cell line. This results in 2140 transcripts mapping to 1871 unique cell cycle–regulated genes that show periodic oscillations across multiple synchronous cell cycles. We identify genomic loci bound by the G2/M transcription factor FOXM1 by chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) and associate these with cell cycle–regulated genes. FOXM1 is bound to cell cycle–regulated genes with peak expression in both S phase and G2/M phases. We show that ChIP-seq genomic loci are responsive to FOXM1 using a real-time luciferase assay in live cells, showing that FOXM1 strongly activates promoters of G2/M phase genes and weakly activates those induced in S phase. Analysis of ChIP-seq data from a panel of cell cycle transcription factors (E2F1, E2F4, E2F6, and GABPA) from the Encyclopedia of DNA Elements and ChIP-seq data for the DREAM complex finds that a set of core cell cycle genes regulated in both U2OS and HeLa cells are bound by multiple cell cycle transcription factors. These data identify the cell cycle–regulated genes in a second cancer-derived cell line and provide a comprehensive picture of the transcriptional regulatory systems controlling periodic gene expression in the human cell division cycle. PMID:24109597

  8. 77 FR 1889 - Federal Acquisition Regulation; Set-Asides for Small Business; Extension of Comment Period

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-12

    ... addresses set-asides of task- and delivery-orders under multiple-award contracts, partial set-asides under... implementation of section 1331 authorities. The comment period is being extended to provide additional time for... time for interested parties to review and submit comments on the published FAR changes until February...

  9. Medicare program; redesignation of reasonable cost regulations--HCFA. Final rule with comment period.

    PubMed

    1986-09-30

    This rule redesignated most of the sections in Subpart D of 42 CFR Part 405 into a new Part 413. This redesignation is part of our overall plan for reorganization of the regulations in 42 CFR Part 405 in order to make them easier to locate and use. More specifically, we intend this redesignation to provide more adequate space for the complex policies and procedures regarding reasonable cost reimbursement that currently are compressed into Part 405, Subpart D.

  10. Internal strain drives spontaneous periodic buckling in collagen and regulates remodeling.

    PubMed

    Dittmore, Andrew; Silver, Jonathan; Sarkar, Susanta K; Marmer, Barry; Goldberg, Gregory I; Neuman, Keir C

    2016-07-26

    Fibrillar collagen, an essential structural component of the extracellular matrix, is remarkably resistant to proteolysis, requiring specialized matrix metalloproteinases (MMPs) to initiate its remodeling. In the context of native fibrils, remodeling is poorly understood; MMPs have limited access to cleavage sites and are inhibited by tension on the fibril. Here, single-molecule recordings of fluorescently labeled MMPs reveal cleavage-vulnerable binding regions arrayed periodically at ∼1-µm intervals along collagen fibrils. Binding regions remain periodic even as they migrate on the fibril, indicating a collective process of thermally activated and self-healing defect formation. An internal strain relief model involving reversible structural rearrangements quantitatively reproduces the observed spatial patterning and fluctuations of defects and provides a mechanism for tension-dependent stabilization of fibrillar collagen. This work identifies internal-strain-driven defects that may have general and widespread regulatory functions in self-assembled biological filaments.

  11. Internal strain drives spontaneous periodic buckling in collagen and regulates remodeling

    PubMed Central

    Dittmore, Andrew; Silver, Jonathan; Sarkar, Susanta K.; Marmer, Barry; Goldberg, Gregory I.; Neuman, Keir C.

    2016-01-01

    Fibrillar collagen, an essential structural component of the extracellular matrix, is remarkably resistant to proteolysis, requiring specialized matrix metalloproteinases (MMPs) to initiate its remodeling. In the context of native fibrils, remodeling is poorly understood; MMPs have limited access to cleavage sites and are inhibited by tension on the fibril. Here, single-molecule recordings of fluorescently labeled MMPs reveal cleavage-vulnerable binding regions arrayed periodically at ∼1-µm intervals along collagen fibrils. Binding regions remain periodic even as they migrate on the fibril, indicating a collective process of thermally activated and self-healing defect formation. An internal strain relief model involving reversible structural rearrangements quantitatively reproduces the observed spatial patterning and fluctuations of defects and provides a mechanism for tension-dependent stabilization of fibrillar collagen. This work identifies internal–strain-driven defects that may have general and widespread regulatory functions in self-assembled biological filaments. PMID:27402741

  12. Peer attachment formation by systemic redox regulation with social training after a sensitive period

    PubMed Central

    Koshiba, Mamiko; Karino, Genta; Senoo, Aya; Mimura, Koki; Shirakawa, Yuka; Fukushima, Yuta; Obara, Saya; Sekihara, Hitomi; Ozawa, Shimpei; Ikegami, Kentaro; Ueda, Toyotoshi; Yamanouchi, Hideo; Nakamura, Shun

    2013-01-01

    Attachment formation is the most pivotal factor for humans and animals in the growth and development of social relationships. However, the developmental processes of attachment formation mediated by sensory-motor, emotional, and cognitive integration remain obscure. Here we developed an animal model to understand the types of social interactions that lead to peer-social attachment formation. We found that the social interaction in a sensitive period was essential to stabilise or overwrite the initially imprinted peer affiliation state and that synchronised behaviour with others based on common motivations could be a driver of peer social attachment formation. Furthermore, feeding experience with supplementation of ubiquinol conferred peer social attachment formation even after the sensitive period. Surprisingly, the experience of feeding beyond the cage window was also effective to reduce the required amount ubiquinol, suggesting that peri-personal space modulation may affect socio-emotional cognition and there by lead to attachment formation. PMID:23974241

  13. Peer attachment formation by systemic redox regulation with social training after a sensitive period.

    PubMed

    Koshiba, Mamiko; Karino, Genta; Senoo, Aya; Mimura, Koki; Shirakawa, Yuka; Fukushima, Yuta; Obara, Saya; Sekihara, Hitomi; Ozawa, Shimpei; Ikegami, Kentaro; Ueda, Toyotoshi; Yamanouchi, Hideo; Nakamura, Shun

    2013-01-01

    Attachment formation is the most pivotal factor for humans and animals in the growth and development of social relationships. However, the developmental processes of attachment formation mediated by sensory-motor, emotional, and cognitive integration remain obscure. Here we developed an animal model to understand the types of social interactions that lead to peer-social attachment formation. We found that the social interaction in a sensitive period was essential to stabilise or overwrite the initially imprinted peer affiliation state and that synchronised behaviour with others based on common motivations could be a driver of peer social attachment formation. Furthermore, feeding experience with supplementation of ubiquinol conferred peer social attachment formation even after the sensitive period. Surprisingly, the experience of feeding beyond the cage window was also effective to reduce the required amount ubiquinol, suggesting that peri-personal space modulation may affect socio-emotional cognition and there by lead to attachment formation.

  14. Hormonal regulation of fluid and electrolyte metabolism during periods of headward fluid shifts

    NASA Technical Reports Server (NTRS)

    Keil, Lanny C.; Severs, W. B.; Thrasher, T.; Ramsay, D. J.

    1991-01-01

    In the broadest sense, this project evaluates how spaceflight induced shifts of blood and interstitial fluids into the thorax affect regulation by the central nervous system (CNS) of fluid-electrolyte hormone secretion. Specifically, it focuses on the role of hormones related to salt/water balance and their potential function in the control of intracranial pressure and cerebrospinal fluid (CSF) composition. Fluid-electrolyte status during spaceflight gradually equilibrates, with a reduction in all body fluid compartments. Related to this is the cardiovascular deconditioning of spaceflight which is manifested upon return to earth as orthostatic intolerance.

  15. Expression and regulation of Runx3 in mouse uterus during the peri-implantation period.

    PubMed

    Bai, Zhi-Kun; Guo, Bin; Tian, Xue-Chao; Li, Dang-Dang; Wang, Shou-Tang; Cao, Hang; Wang, Qu-Yuan; Yue, Zhan-Peng

    2013-10-01

    The aim of this study was to investigate the differential expression and regulation of Runt-related transcription factor 3 (Runx3) in mouse uterus during early pregnancy and its regulation by steroid hormones using in situ hybridization. There was a low level of the Runx3 mRNA expression in the mouse uterus on days 1-4 of pregnancy. On day 5 when embryo implanted, Runx3 mRNA signal was obviously observed in the stromal cells surrounding the implanting blastocyst. From day 6 to 8 of pregnancy, Runx3 mRNA was highly expressed in the decidual cells and mesometrial decidual beds. Similarly, Runx3 mRNA was strongly expressed in decidualized cells under artificial decidualization. Compared with the delayed uterus, a high level of Runx3 mRNA signal was detected in the uterus with activated implantation. In the ovariectomized mouse uterus, estrogen could induce the expression of Runx3, while progesterone had no effects. These results suggest that Runx3 may play an important role during mouse implantation and decidualization. Estrogen can induce the expression of Runx3 in the ovariectomized mouse uterus.

  16. Periodic variation in R-R intervals and cardiovascular autonomic regulation in young adult Syrian hamsters.

    PubMed

    Mongue-Din, H; Salmon, A; Fiszman, M Y; Fromes, Y

    2009-03-01

    Several hamster strains are commonly used as models for cardiomyopathic phenotypes evolving toward heart failure. However, little is known about heart rate variability (HRV) in this species. Prolonged surface ECG recording, a prerequisite to HRV studies, can be obtained either by telemetry or by restraints. Here, we performed long time ECG recording using telemetry on young adult Syrian hamsters and we analyzed time series of interbeat intervals. Standard statistics showed that the mean of normal R-R intervals slightly increased with age, with standard deviation of normal R-R intervals remaining stable over time. However, time domain analysis using Poincaré plots revealed dynamic changes in the HRV. Analysis of frequency domains revealed that the ratio of spectral components (low frequency/high frequency) exhibited a maturation pattern. Thus refined analysis of HRV revealed a more complex pattern than common statistical analysis would translate. Unlike other rodents, hamsters display a great spontaneous variability of their heart rate. As the complexity canvas of HRV might be the consequence of extracardiac regulation factors, we assessed the sympathovagal balance in both time and frequency domain of heart rate. Pharmacological tests revealed that both sympathetic and vagal tones contribute to HRV in Syrian hamsters. Thus Syrian hamsters have a broad intrinsic HRV with large influences of the neurovegetative system. However, the influence of the previous beat seems to prevail over the autonomic oscillators. These animals present a high sensitivity to artificially altered cardiac regulation and might be great models for the diagnosis of early alterations in the HRV related to pathology. Therefore, Syrian hamsters represent a unique model for HRV studies.

  17. Calcitonin gene-related peptide (CGRP) regulates excitability and refractory period of the guinea pig ureter.

    PubMed

    Maggi, C A; Giuliani, S

    1994-08-01

    Previous studies have indicated that calcitonin gene-related peptide (CGRP), released from the peripheral endings of capsaicin-sensitive primary afferent neurons, may play a role as an inhibitory transmitter in the guinea pig ureter. The aim of this study was to compare the effect of capsaicin desensitization and administration of a CGRP receptor antagonist on the excitability and refractory period of the guinea pig ureter to electrical field stimulation. Electrical field stimulation using a long (5 msec.) pulse width produced phasic contractions of the ureter which were unaffected by tetrodotoxin, that is, were produced through direct excitation of ureteral smooth muscle. Human alpha CGRP (1 to 10 nM.) produced a concentration-dependent transient suppression of the evoked contractions, and its effect was prevented by the CGRP receptor antagonist human alpha CGRP(8-37) (1 microM.). In vitro capsaicin pretreatment (10 microM. for 15 minutes) to block neuropeptide release from peripheral endings of sensory nerves or administration of the CGRP receptor antagonist enhanced the responsiveness of the guinea pig ureter to electrical stimulation. In control ureters, the application of two trains of electrical stimuli failed to produce a second contraction at intertrain intervals greater than 20 seconds. The intertrain interval required to obtain a second contraction averaging 50% of the amplitude of the first response (ITI50) of control ureters was about 50 seconds. In vitro capsaicin pretreatment or administration of the CGRP receptor antagonist reduced the refractory period of the ureter to electrical field stimulation: ITI50 averaged 8.8 and 9.1 seconds after capsaicin or CGRP antagonist pretreatment, respectively. These findings demonstrate that capsaicin pretreatment or blockade of CGRP receptors produced qualitatively and quantitatively similar excitatory effects on ureteral excitability and refractory period and are in general agreement with the idea that CGRP is a

  18. Regulation of muscle stiffness during periodic length changes in the isolated abdomen of the hermit crab.

    PubMed

    Chapple, W D

    1997-09-01

    Reflex activation of the ventral superficial muscles (VSM) in the abdomen of the hermit crab, Pagurus pollicarus, was studied using sinusoidal and stochastic longitudinal vibration of the muscle while recording the length and force of the muscle and the spike times of three exciter motoneurons. In the absence of vibration, the interspike interval histograms of the two larger motoneurons were bimodal; cutting sensory nerves containing most of the mechanoreceptor input removed the short interval peak in the histogram, indicating that the receptors are important in maintaining tonic firing. Vibration of the muscle evoked a reflex increase in motoneuron frequency that habituated after an initial peak but remained above control levels for the duration of stimulation. Motoneuron frequency increased with root mean square (rms) stimulus amplitude. Average stiffness during stimulation was about two times the stiffness of passive muscle. The reflex did not alter muscle dynamics. Estimated transfer functions were calculated from the fast Fourier transform of length and force signals. Coherence was >0.9 for the frequency range of 3-35 Hz. Stiffness magnitude gradually increased over this range in both reflex activated and passive muscle; phase was between 10 and 20 degrees. Reflex stiffness decreased with increasing stimulus amplitudes, but at larger amplitudes, this decrease was much less pronounced; in this range stiffness was regulated by the reflex. The sinusoidal frequency at which reflex bursts were elicited was approximately 6 Hz, consistent with previous measurements using ramp stretch. During reflex excitation, there was an increase in amplitude of the short interval peak in the interspike interval histogram; this was reduced when the majority of afferent pathways was removed. A phase histogram of motoneuron firing during sinusoidal vibration had a peak at approximately 110 ms, also suggesting that an important component of the reflex is via direct projections from

  19. Differential expression and regulation of angiopoietin-2 in mouse uterus during preimplantation period.

    PubMed

    Guo, Bin; Wang, Wei; Li, Shi-Jie; Han, Yu-Shuai; Zhang, Lu; Zhang, Xue-Ming; Liu, Ju-Xiong; Yue, Zhan-Peng

    2012-02-01

    Angiogenesis is crucial to successful implantation and decidualization, however, as an important angiogenic growth factor, the effect of Ang-2 in the process of implantation and decidualization is still unknown. This study is to investigate the differential expression of Ang-2 in mouse uterus during early pregnancy and its regulation by steroid hormones using in situ hybridization and RT-PCR. There is no detectable Ang-2 mRNA signal on days 1-5 of pregnancy by in situ hybridization. On days 6-8, Ang-2 mRNA is mainly expressed in the primary decidua of mesometrial side, and the expression gradually increases. By RT-PCR, a significantly higher level of Ang-2 expression is observed on day 8 of pregnancy, although Ang-2 expression can be found through days 1-8. Similarly, Ang-2 is highly expressed in decidualized cells under artificial decidualization. In the ovariectomized mouse uterus, Ang-2 expression gradually increases after estrogen injection and with peak levels at 12 hr, while progesterone injection can cause a decline in uterine Ang-2 mRNA level, which reaches a nadir at 12 hr. These results suggest that Ang-2 may play a key role in the process of mouse decidualization. Estrogen can induce the expression of Ang-2 while progesterone can inhibit its expression in the ovariectomized mouse uterus.

  20. Differential expression and regulation of angiopoietin-3 in mouse uterus during preimplantation period.

    PubMed

    Guo, Bin; Zhang, Xue-Ming; Li, Shi-Jie; Tian, Xue-Chao; Wang, Shou-Tang; Li, Dang-Dang; Liu, Ju-Xiong; Yue, Zhan-Peng

    2012-06-01

    Angiogenesis is necessary for successful implantation and decidualization. This study was to investigate the differential expression of angiopoietin-3 (Ang-3) in mouse uterus during early pregnancy and its regulation by steroid hormones using in situ hybridization and reverse transcription polymerase chain reaction (RT-PCR). There was no detectable Ang-3 mRNA signal on days 1-5 of pregnancy by in situ hybridization. On day 6 of pregnancy, a low level of Ang-3 mRNA signal was seen in the primary decidua. Ang-3 mRNA expression gradually increased on days 7 and 8 of pregnancy along with the development of decidua, and its expression scope was also expanded. The RT-PCR result indicated that Ang-3 mRNA expression was low on days 1-4 of pregnancy. On day 5, as embryo implanted, Ang-3 mRNA was highly expressed in mouse uterus, and the expression gradually increased on days 6-8 of pregnancy, with peak level on day 8 of pregnancy. Similarly, Ang-3 mRNA was also strongly expressed in decidualized cells under artificial decidualization. Compared with the delayed uterus, a high level of Ang-3 mRNA expression was detected in activated implantation uterus by RT-PCR. In the ovariectomized mouse uterus, Ang-3 mRNA expression increased and reached the highest level at 12 hr after injection of estrogen, progesterone, and estrogen plus progesterone, respectively. These results suggest that Ang-3 may play an important role during the process of mouse decidualization. Both estrogen and progesterone can induce the expression of Ang-3 in ovariectomized mouse uterus.

  1. The circadian protein period 1 contributes to blood pressure control and coordinately regulates renal sodium transport genes.

    PubMed

    Stow, Lisa R; Richards, Jacob; Cheng, Kit-Yan; Lynch, I Jeanette; Jeffers, Lauren A; Greenlee, Megan M; Cain, Brian D; Wingo, Charles S; Gumz, Michelle L

    2012-06-01

    The circadian clock protein period 1 (Per1) contributes to the regulation of expression of the α subunit of the renal epithelial sodium channel at the basal level and in response to the mineralocorticoid hormone aldosterone. The goals of the present study were to define the role of Per1 in the regulation of additional renal sodium handling genes in cortical collecting duct cells and to evaluate blood pressure (BP) in mice lacking functional Per1. To determine whether Per1 regulates additional genes important in renal sodium handling, a candidate gene approach was used. Immortalized collecting duct cells were transfected with a nontarget small interfering RNA or a Per1-specific small interfering RNA. Expression of the genes for α-epithelial sodium channel and Fxyd5, a positive regulator of Na, K-ATPase activity, decreased in response to Per1 knockdown. Conversely, mRNA expression of caveolin 1, Ube2e3, and ET-1, all negative effectors of epithelial sodium channel, was induced after Per1 knockdown. These results led us to evaluate BP in Per1 KO mice. Mice lacking Per1 exhibit significantly reduced BP and elevated renal ET-1 levels compared with wild-type animals. Given the established role of renal ET-1 in epithelial sodium channel inhibition and BP control, elevated renal ET-1 is one possible explanation for the lower BP observed in Per1 KO mice. These data support a role for the circadian clock protein Per1 in the coordinate regulation of genes involved in renal sodium reabsorption. Importantly, the lower BP observed in Per1 KO mice compared with wild-type mice suggests a role for Per1 in BP control as well.

  2. Regulation of Intertidal Microphytobenthos Photosynthesis Over a Diel Emersion Period Is Strongly Affected by Diatom Migration Patterns

    PubMed Central

    Cartaxana, Paulo; Cruz, Sónia; Gameiro, Carla; Kühl, Michael

    2016-01-01

    Changes in biomass and photosynthesis of a diatom-dominated microphytobenthos (MPB) intertidal community were studied over a diel emersion period using a combination of O2 and scalar irradiance microprofiling, variable chlorophyll (Chl) fluorescence, and pigment analysis. The MPB biomass in the photic zone (0–0.5 mm) of the sediment exposed to low irradiance (150 μmol photons m-2 s-1) showed a >2-fold increase during the first hours of the emersion period, reaching >0.2 mg Chl a cm-3. Concentrations of Chl a started to decrease half-way through the emersion period, almost 2 h before tidal inundation. Similarly, O2 concentrations and volumetric gross photosynthesis in the photic zone increased during the first half of the emersion period and then decreased toward the timing of incoming tide/darkness. The results suggest that intertidal MPB community-level photosynthesis is mainly controlled by changes in the productive biomass of the photic zone determined by cell migration. A diel pattern in the photosynthesis vs. irradiance parameters α (photosynthetic efficiency at limiting irradiance) and ETRmax (photosynthetic capacity at saturating irradiance) was also observed, suggesting photoacclimation of MPB. Under high light exposure (2000 μmol photons m-2 s-1), lower α, ETRmax and sediment O2 concentrations were observed when cell migration was inhibited with the diatom motility inhibitor latrunculin A (Lat A), showing that migration is also used by MPB to maximize photosynthesis by reducing exposure to potentially photoinhibitory light levels. A higher de-epoxidation state in sediment treated with Lat A indicates that the involvement of the xanthophyll cycle in physiological photoprotection is more relevant in MPB when cells are inhibited from migrating. In the studied diatom-dominated MPB intertidal community, cell migration seems to be the key factor regulating photosynthesis over a diel emersion period and upon changes in light exposure. PMID:27375593

  3. Regulation of Intertidal Microphytobenthos Photosynthesis Over a Diel Emersion Period Is Strongly Affected by Diatom Migration Patterns.

    PubMed

    Cartaxana, Paulo; Cruz, Sónia; Gameiro, Carla; Kühl, Michael

    2016-01-01

    Changes in biomass and photosynthesis of a diatom-dominated microphytobenthos (MPB) intertidal community were studied over a diel emersion period using a combination of O2 and scalar irradiance microprofiling, variable chlorophyll (Chl) fluorescence, and pigment analysis. The MPB biomass in the photic zone (0-0.5 mm) of the sediment exposed to low irradiance (150 μmol photons m(-2) s(-1)) showed a >2-fold increase during the first hours of the emersion period, reaching >0.2 mg Chl a cm(-3). Concentrations of Chl a started to decrease half-way through the emersion period, almost 2 h before tidal inundation. Similarly, O2 concentrations and volumetric gross photosynthesis in the photic zone increased during the first half of the emersion period and then decreased toward the timing of incoming tide/darkness. The results suggest that intertidal MPB community-level photosynthesis is mainly controlled by changes in the productive biomass of the photic zone determined by cell migration. A diel pattern in the photosynthesis vs. irradiance parameters α (photosynthetic efficiency at limiting irradiance) and ETR max (photosynthetic capacity at saturating irradiance) was also observed, suggesting photoacclimation of MPB. Under high light exposure (2000 μmol photons m(-2) s(-1)), lower α, ETR max and sediment O2 concentrations were observed when cell migration was inhibited with the diatom motility inhibitor latrunculin A (Lat A), showing that migration is also used by MPB to maximize photosynthesis by reducing exposure to potentially photoinhibitory light levels. A higher de-epoxidation state in sediment treated with Lat A indicates that the involvement of the xanthophyll cycle in physiological photoprotection is more relevant in MPB when cells are inhibited from migrating. In the studied diatom-dominated MPB intertidal community, cell migration seems to be the key factor regulating photosynthesis over a diel emersion period and upon changes in light exposure.

  4. Phospholemman, a major regulator of skeletal muscle Na+/K+-ATPase, is not mutated in probands with hypokalemic periodic paralysis

    PubMed Central

    Chen, Ying-Ying; Wang, Xiao-Ying; Fu, Qiu-Xia; Kang, Yi; Yao, He-Bin

    2017-01-01

    The pathogenesis of hypokalemic periodic paralysis (HypoPP) remains unclear. Though some mutations in skeletal muscle ion channels were revealed previously, the exact mechanism remains to be fully elucidated. Increased Na+/K+-ATPase activity in skeletal muscle is postulated to contribute to attacks of HypoPP. Before the link between Na+/K+-ATPase dysfunction and these ion channel mutations is established, mutations in Na+/K+-ATPase and their regulators are the first to be excluded. Phospholemman, which is a protein encoded by the FXYD domain-containing ion transport regulator 1 (FXYD1) gene, is predominantly expressed in skeletal muscle and is the major regulator of Na+/K+-ATPase. Therefore, the aim of the present study was to determine the genetic involvement of phospholemman in HypoPP development. Genomic DNA was extracted from the peripheral blood of five HypoPP probands with typical manifestations. The coding exons of FXYD1, exons 2–7, were polymerase chain reaction (PCR)-amplified and sequenced. No mutations were detected in FXYD1 in any of the subjects studied. To conclude, mutations in phospholemman encoding genes may not be involved with HypoPP and the relationship between phospholemman and Na+/K+-ATPase dysfunction in attacks of HypoPP requires further study. PMID:28912873

  5. Downstream activation of NF‐κB in the EDA‐A1/EDAR signalling in Sjögren's syndrome and its regulation by the ubiquitin‐editing enzyme A20

    PubMed Central

    Barca, A.; Lofrumento, D. D.; Lisi, S.

    2016-01-01

    Summary Sjögren's syndrome (SS) is an autoimmune disease and the second most common chronic systemic rheumatic disorder. Prevalence of primary SS in the general population has been estimated to be approximately 1–3%, whereas secondary SS has been observed in 10–20% of patients with rheumatoid arthritis, systemic lupus erythematosus (SLE) and scleroderma. Despite this, its exact aetiology and pathogenesis are largely unexplored. Nuclear factor‐kappa B (NF‐κB) signalling mechanisms provide central controls in SS, but how these pathways intersect the pathological features of this disease is unclear. The ubiquitin‐editing enzyme A20 (tumour necrosis factor‐α‐induced protein 3, TNFAIP3) serves as a critical inhibitor on NF‐κB signalling. In humans, polymorphisms in the A20 gene or a deregulated expression of A20 are often associated with several inflammatory disorders, including SS. Because A20 controls the ectodysplasin‐A1 (EDA‐A1)/ectodysplasin receptor (EDAR) signalling negatively, and the deletion of A20 results in excessive EDA1‐induced NF‐κB signalling, this work investigates the expression levels of EDA‐A1 and EDAR in SS human salivary glands epithelial cells (SGEC) and evaluates the hypothesis that SS SGEC‐specific deregulation of A20 results in excessive EDA1‐induced NF‐κB signalling in SS. Our approach, which combines the use of siRNA‐mediated gene silencing and quantitative pathway analysis, was used to elucidate the role of the A20 target gene in intracellular EDA‐A1/EDAR/NF‐κB pathway in SS SGEC, holding significant promise for compound selection in drug discovery. PMID:26724675

  6. Experience Affects Critical Period Plasticity in the Visual Cortex through an Epigenetic Regulation of Histone Post-Translational Modifications.

    PubMed

    Baroncelli, Laura; Scali, Manuela; Sansevero, Gabriele; Olimpico, Francesco; Manno, Ilaria; Costa, Mario; Sale, Alessandro

    2016-03-23

    During an early phase of enhanced sensitivity called the critical period (CP), monocular deprivation causes a shift in the response of visual cortex binocular neurons in favor of the nondeprived eye, a process named ocular dominance (OD) plasticity. While the time course of the CP for OD plasticity can be modulated by genetic/pharmacological interventions targeting GABAergic inhibition, whether an increased sensory-motor experience can affect this major plastic phenomenon is not known. We report that exposure to environmental enrichment (EE) accelerated the closure of the CP for OD plasticity in the rat visual cortex. Histone H3 acetylation was developmentally regulated in primary visual cortex, with enhanced levels being detectable early in enriched pups, and chromatin immunoprecipitation revealed an increase at the level of the BDNF P3 promoter. Administration of the histone deacetylase inhibitor SAHA (suberoylanilide hydroxamic acid) to animals reared in a standard cage mimicked the increase in H3 acetylation observed in the visual cortex and resulted in an accelerated decay of OD plasticity. Finally, exposure to EE in adulthood upregulated H3 acetylation and was paralleled by a reopening of the CP. These findings demonstrate a critical involvement of the epigenetic machinery as a mediator of visual cortex developmental plasticity and of the impact of EE on OD plasticity. While it is known that an epigenetic remodeling of chromatin structure controls developmental plasticity in the visual cortex, three main questions have remained open. Which is the physiological time course of histone modifications? Is it possible, by manipulating the chromatin epigenetic state, to modulate plasticity levels during the critical period? How can we regulate histone acetylation in the adult brain in a noninvasive manner? We show that the early exposure of rat pups to enriching environmental conditions accelerates the critical period for plasticity in the primary visual cortex

  7. Expression and regulation of lanosterol 14alpha-demethylase in mouse embryo and uterus during the peri-implantation period.

    PubMed

    Song, Xiaoming; Tai, Ping; Yan, Jun; Xu, Baoshan; Chen, Xiufen; Ouyang, Hong; Zhang, Meijia; Xia, Guoliang

    2008-01-01

    Lanosterol 14alpha-demethylase (LDM) is expressed ubiquitously in all mammals and is important in cholesterol biosynthesis. However, whether LDM expression is involved in the interaction between uterus and embryo during implantation remains unknown. In the present study, the expression of LDM was investigated in mouse embryo and uterus during the peri-implantation period using confocal microscopy, immunohistochemistry and western blot methods. Further, regulation of LDM expression was investigated in pseudopregnancy, delayed implantation, artificial decidualisation and ovariectomisation using 17beta-oestradiol and progesterone treatment mouse models. The results showed that LDM was selectively expressed in preimplantation embryos and the uterine subluminal stroma surrounding the implanting blastocyst on Day 5 of pregnancy. No corresponding signal was detected in the uterus on Day 5 of pseudopregnancy. Most notably, once delayed implantation was terminated by oestrogen treatment and the embryo implanted, a high level of LDM expression was induced in the subluminal stroma surrounding the implanting blastocyst, whereas no corresponding signal was detected in the delayed implantation uterus. A high level of LDM expression was observed in the uterus decidua on Days 6-8 of pregnancy. Furthermore, LDM expression was induced in the uterine stroma under artificial decidualisation. Oestrogen, but not progesterone, treatment induced a high level of LDM expression in the uterus of ovariectomised mice. These results indicate that LDM is closely related to mouse embryo implantation and can be upregulated by oestrogen.

  8. Extracellular Ca2+-sensing receptor expression and hormonal regulation in rat uterus during the peri-implantation period.

    PubMed

    Xiao, Li-Juan; Yuan, Jin-Xiang; Li, Yin-Chuan; Wang, Rui; Hu, Zhao-Yuan; Liu, Yi-Xun

    2005-06-01

    The extracellular Ca2+-sensing receptor (CaR) is a member of the superfamily of G protein-coupled receptors (GPCRs). It is an important mediator of a wide range of Ca2+-dependent physiological responses in various tissues. In reproductive tissues it has been reported to play a significant role in promoting or maintaining placentation. Meanwhile, another Ca2+ regulated gene stanniocalcin-1 (STC-1) has been documented to be involved in decidualization and uterine remodelling. The phenomenon that CaR mediates STC-1's transcription responding to extracellular calcium in fish urges us to suppose that CaR, like STC-1, may also play a role in implantation and decidualization. To resolve this conjecture, we have examined the expression and hormonal regulation of the CaR gene in rat uterus during peri-implantation period. CaR mRNA was expressed at a moderate level in the luminal epithelium of the early stage of pregnancy (from day 1 to day 3). From day 2-3 it began to be expressed more strongly in the stromal cells immediately underneath the luminal epithelium, but decreased to a basal level on day 4. From day 6 to day 9 continuously, both CaR mRNA and protein were highly expressed in the primary decidua. Expression of CaR mRNA and protein in these cells was also observed when a delayed implantation was terminated by estrogen treatment to allow the embryo implantation. In contrast, only basal level expression of the molecules was detected in the cells of animals subjected to a normal-delayed implantation or the pseudopregnant condition. Embryo transplantation experiment confirmed that CaR expression at the implantation site was induced by the implanting blastocyst. Consistent with the normal pregnant process, CaR mRNA and protein in the cells were also induced by an artificial decidualization procedure. Further experiments demonstrated that treatment of the ovariectomized rat with estrogen or/and progesterone stimulated a high level expression of CaR mRNA in the uterine

  9. The maturation-inducing hormone 17a-20b-dihydroxy-4pregnen-3-one regulates gene expression of inhibin A and bambi (bone morphogenetic protein and activin membrane bound inhibitor) in the rainbow trout ovary

    USDA-ARS?s Scientific Manuscript database

    Transforming growth factor-beta (TGFb) superfamily members are important paracrine and autocrine regulators of ovarian development and steroidogenesis in mammals and birds, but their reproductive roles in fish are not well understood. The activin system, Tgfb, and bone morphogenetic protein 15 (Bmp...

  10. Differential effects of NT-4, NGF and BDNF on development of neurochemical architecture and cell size regulation in rat visual cortex during the critical period.

    PubMed

    Engelhardt, Maren; Di Cristo, Graziella; Berardi, Nicoletta; Maffei, Lamberto; Wahle, Petra

    2007-01-01

    Development of inhibition is a crucial determinant of the time course of visual cortical plasticity. BDNF strongly affects interneuron development and the onset and closure of the critical period for ocular dominance plasticity. Less is known on the effects of NT-4 despite a clear involvement in ocular dominance plasticity. We have investigated the effects of NT-4 on interneuron development by supplying NT-4 with osmotic minipumps during two time windows overlapping the onset (P12-20) and the peak (P20-28) of the critical period. We assessed the expression of interneuronal markers and soma size maturation either after the end of the infusion periods or at the end of the critical period (P45). We found that NT-4 was very effective in regulating interneuron development. NPY, SOM and PARV neuron somata grew faster during both infusion periods whereas CR neurons only responded during the early infusion period. The effects of soma size elicited during the earlier infusion period were still present at P45. In PARV neurons, NT-4 caused a long-lasting stabilization of CB and NPY expression. Furthermore, NT-4 accelerated the expression of GAD-65 mRNA in a subset of non-PARV neurons of layer V, which normally up-regulate GAD-65 towards the end of the critical period. Most of these effects were shared by NT-4 and BDNF. Some were unexpectedly also shared by NGF, which promoted growth of layer V PARV neurons, stabilized the CB expression and accelerated the GAD-65 expression. The results suggest that neurotrophins act on critical period plasticity by strengthening inhibition.

  11. Elder homicide: a 20-year study.

    PubMed

    Collins, Kim A; Presnell, S Erin

    2006-06-01

    A subcategory of elder maltreatment is the fatal outcome, or elder homicide. Some cases of elder homicide result from chronic abuse and/or neglect, while others appear to be sudden, with no pertinent history. The research and literature of elder homicide are lacking, making the investigation of each case difficult; the typical victim, perpetrator, scenario, and cause of death are not known. Components of homicide such as sexual assault and toxicology also lack study. We analyzed all elder deaths over a 20-year period. Cases included those with victims greater than or equal to 65 years of age. These deaths totaled 2137: natural = 1506, accident = 344, suicide = 139, homicide = 127, and undetermined = 21. Focusing on homicides, variables analyzed were age, race, gender, cause of death, location of death, time of year, motive, perpetrator, toxicology, and sexual assault component. By identifying the typical victim, perpetrator, scenario, and autopsy findings, these cases can be more completely investigated and possibly prevented.

  12. Sustained Attention Development during the Toddlerhood to Preschool Period: Associations with Toddlers' Emotion Regulation Strategies and Maternal Behaviour

    ERIC Educational Resources Information Center

    Graziano, Paulo A.; Calkins, Susan D.; Keane, Susan P.

    2011-01-01

    The current study examined the role of maternal behaviour and toddlers' emotion regulation strategies in the development of children's sustained attention abilities. Participants for this study included 447 children (232 girls) obtained from three different cohorts participating in a larger ongoing longitudinal study. When the children were 2…

  13. 78 FR 61222 - Amendments to Regulation D, Form D and Rule 156; Re-Opening of Comment Period

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-03

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE... amendments. DATES: The comment period for the proposed rule published at 78 FR 44806 on July 24, 2013, is... help us process and review your comments more efficiently, please use only one method. The Commission...

  14. Using generalized linear models to estimate selectivity from short-term recoveries of tagged red drum Sciaenops ocellatus: Effects of gear, fate, and regulation period

    USGS Publications Warehouse

    Bacheler, N.M.; Hightower, J.E.; Burdick, S.M.; Paramore, L.M.; Buckel, J.A.; Pollock, K.H.

    2010-01-01

    Estimating the selectivity patterns of various fishing gears is a critical component of fisheries stock assessment due to the difficulty in obtaining representative samples from most gears. We used short-term recoveries (n = 3587) of tagged red drum Sciaenops ocellatus to directly estimate age- and length-based selectivity patterns using generalized linear models. The most parsimonious models were selected using AIC, and standard deviations were estimated using simulations. Selectivity of red drum was dependent upon the regulation period in which the fish was caught, the gear used to catch the fish (i.e., hook-and-line, gill nets, pound nets), and the fate of the fish upon recovery (i.e., harvested or released); models including all first-order interactions between main effects outperformed models without interactions. Selectivity of harvested fish was generally dome-shaped and shifted toward larger, older fish in response to regulation changes. Selectivity of caught-and-released red drum was highest on the youngest and smallest fish in the early and middle regulation periods, but increased on larger, legal-sized fish in the late regulation period. These results suggest that catch-and-release mortality has consistently been high for small, young red drum, but has recently become more common in larger, older fish. This method of estimating selectivity from short-term tag recoveries is valuable because it is simpler than full tag-return models, and may be more robust because yearly fishing and natural mortality rates do not need to be modeled and estimated. ?? 2009 Elsevier B.V.

  15. Using generalized linear models to estimate selectivity from short-term recoveries of tagged red drum Sciaenops ocellatus: Effects of gear, fate, and regulation period

    USGS Publications Warehouse

    Burdick, Summer M.; Hightower, Joseph E.; Bacheler, Nathan M.; Paramore, Lee M.; Buckel, Jeffrey A.; Pollock, Kenneth H.

    2010-01-01

    Estimating the selectivity patterns of various fishing gears is a critical component of fisheries stock assessment due to the difficulty in obtaining representative samples from most gears. We used short-term recoveries (n = 3587) of tagged red drum Sciaenops ocellatus to directly estimate age- and length-based selectivity patterns using generalized linear models. The most parsimonious models were selected using AIC, and standard deviations were estimated using simulations. Selectivity of red drum was dependent upon the regulation period in which the fish was caught, the gear used to catch the fish (i.e., hook-and-line, gill nets, pound nets), and the fate of the fish upon recovery (i.e., harvested or released); models including all first-order interactions between main effects outperformed models without interactions. Selectivity of harvested fish was generally dome-shaped and shifted toward larger, older fish in response to regulation changes. Selectivity of caught-and-released red drum was highest on the youngest and smallest fish in the early and middle regulation periods, but increased on larger, legal-sized fish in the late regulation period. These results suggest that catch-and-release mortality has consistently been high for small, young red drum, but has recently become more common in larger, older fish. This method of estimating selectivity from short-term tag recoveries is valuable because it is simpler than full tag-return models, and may be more robust because yearly fishing and natural mortality rates do not need to be modeled and estimated.

  16. Developmental Periods of Choline Sensitivity Provide an Ontogenetic Mechanism for Regulating Memory Capacity and Age-Related Dementia

    PubMed Central

    Meck, Warren H.; Williams, Christina L.; Cermak, Jennifer Marie; Blusztajn, Jan Krzysztof

    2008-01-01

    In order to determine brain and behavioral sensitivity of nutrients that may serve as inductive signals during early development, we altered choline availability to rats during 7 time frames spanning embryonic day (ED) 6 through postnatal day (PD) 75 and examined spatial memory ability in the perinatally-treated adults. Two sensitive periods were identified, ED 12–17 and PD 16–30, during which choline supplementation facilitated spatial memory and produced increases in dendritic spine density in CA1 and dentate gyrus (DG) regions of the hippocampus while also changing the dendritic fields of DG granule cells. Moreover, choline supplementation during ED 12–17 only, prevented the memory decline normally observed in aged rats. These behavioral changes were strongly correlated with the acetylcholine (ACh) content of hippocampal slices following stimulated release. Our data demonstrate that the availability of choline during critical periods of brain development influences cognitive performance in adulthood and old age, and emphasize the importance of perinatal nutrition for successful cognitive aging. PMID:18958235

  17. Expression and regulation of cytosolic prostaglandin E synthase in mouse uterus during the peri-implantation period.

    PubMed

    Ni, Hua; Sun, Tong; Ma, Xing-Hong; Yang, Zeng-Ming

    2003-03-01

    Prostaglandin E(2) (PGE(2)) is considered important for blastocyst spacing, implantation, and decidualization in rodent uteri. PGE synthase (PGES) catalyzes the isomerization of PGH(2) to PGE(2). Two isoforms of PGES exist: microsomal PGES (mPGES) and cytosolic PGES (cPGES); however, the expression and regulation of cPGES in the mammalian uterus during early pregnancy are still unknown. The aim of this study was to investigate the differential expression of cPGES in mouse uterus during early pregnancy and its regulation under different conditions using in situ hybridization and immunohistochemistry. A strong level of cPGES mRNA signal was exhibited in the stromal cells at the implantation site on Day 5 of pregnancy, whereas cPGES immunostaining was strongly detected in the luminal epithelium. The signals for both cPGES mRNA and immunostaining were strongly detected in the decidualized cells from Days 6-8 of pregnancy. A basal level of cPGES mRNA signal and immunostaining was exhibited in the uterus in delayed implantation. After delayed implantation was terminated by estrogen treatment and embryo implantation was initiated, cPGES mRNA signal was strongly detected in the stroma underlying the luminal epithelium at the implantation site, and cPGES immunostaining was strongly observed in the luminal epithelium surrounding the implanting blastocyst. A strong cPGES mRNA signal and immunostaining were detected in decidualized cells under artificial decidualization, whereas only a basal level of cPGES mRNA signal and immunostaining were observed in the control horn. Our data suggest that cPGES may play an important role during implantation and decidualization.

  18. [Establishment of the intestinal microflora and regulation of bacterial translocation after caffeine citrate treatment during postnatal period in rat].

    PubMed

    Moumen Chentouf, W; Tir Touil Meddah, A; Léké, A; Mullié, C; Krim, G; Canarelli, J-P; Meddah, B

    2012-10-01

    To relieve respiratory problems such as apnea in newborns, caffeine citrate is the drug of choice because of its good tolerance and therapeutic index. However, its impact on the intestinal microbial ecosystem and on bacterial translocation in the neonatal period remains insufficiently investigated. Therefore, the objective of this study was to evaluate the effects of caffeine citrate on the establishment of the intestinal microflora and bacterial translocation in rats from birth to the 30th day of life. Newborn Wistar rats were divided into four groups of 14 animals, each subdivided into a control group receiving a placebo (12mL tap water/kg/day) and another treated with caffeine citrate (12mg/kg/day). The animals were nursed by their mothers and weighed daily. A group of 14 rats was killed at birth and after 10, 20, or 30 days of life. Organs in which translocation was assessed (liver, lungs, spleen, and kidneys) and various fragments of intestine (duodenum, jejunum, ileum, and colon) were surgically removed. The bacteriological analysis performed involved enumeration of the total microflora, staphylococci, enterobacteria, and lactobacilli. From the 10th day, caffeine was shown to significantly decrease the weight of treated animals as compared with controls (P<0.05). However, caffeine treatment did not drastically alter the kinetics of establishment of the intestinal microflora as only enterobacteria were found to be significantly lower in any intestinal segment of the treated group (P<0.05). Moreover, from the 20th day of life, caffeine citrate significantly downregulated bacterial translocation of both Gram-positive and -negative bacteria (P<0.05). This preliminary study on the effects of treatment with caffeine citrate may open opportunities in clinical pediatrics; the treatment will remain partially effective in preventing bacterial translocation in the neonatal period.

  19. Effects of sex steroid hormones, thyroid hormone levels, and insulin regulation on thyrotoxic periodic paralysis in Chinese men.

    PubMed

    Li, Wang; Changsheng, Chen; Jiangfang, Fu; Bin, Gao; Nanyan, Zhang; Xiaomiao, Li; Deqiang, Li; Ying, Xing; Wensong, Zai; Qiuhe, Ji

    2010-12-01

    Our study is to determine the expression of thyroid hormone, sex hormone, insulin, and C-peptide in Chinese male patients with thyrotoxic periodic paralysis (TPP). This study covered 102 patients with hyperthyroidism from Xijing Hospital. According to whether occurrence of TPP or not, patients were divided into two groups (those that were hyperthyroid with and without TPP) that were, matched with age, blood pressure, urea, and creatinine. We found the body mass index (BMI) in patients with TPP was higher than that in pure hyperthyroidism patients. The levels of the total thyroxine (T4), free triiodothyronine (FT3), and free thyroxine (FT4) were significantly lower in patients with TPP compared with pure hyperthyroidism patients, while serum testosterone levels were higher compared with pure hyperthyroidism patients. Moreover, after glucose administration, the concentration of insulin at 60, 120, and 180 min were significantly higher in patients with TPP than those in pure hyperthyroidism patients. The insulin area under the curve (AUC) was significantly increased in patients with TPP compared with pure hyperthyroidism patients. The levels of thyroid hormone, sex hormone, and insulin were different in Chinese male patients with TPP compared to those with only hyperthyroidism.

  20. Regulation and genetic organization of hydrogenase: Final progress report for the period June 1, 1985--July 31, 1988

    SciTech Connect

    Krasna, A.I.

    1988-10-01

    Hydrogenase is an enzyme which plays an important role in the anaerobic metabolism of many bacteria. The objectives of the research were to elucidate the regulation and genetic organization of hydrogenase in microorganisms. A mutation in the E. coli hydE gene leads to loss of all hydrogenase activities and isoenzymes as well as all formate-related activities. A 0.9 kb DNA fragment has been cloned from an E. coli genomic DNA library which restored all hydrogenase and formate activities to a hydE mutant strain. This gene coded for a polypeptide of subunit mw 36 kDa which is required for hydrogenase synthesis. It is involved in incorporation of nickel into hydrogenase. A mutation in the E coli hupB gene leads to the loss of the uptake of H/sub 2/ by dyes and the ability to grow on fumarate plus H/sub 2/, but expresses normal levels of hydrogenase when assayed by deuterium exchange. This mutation also leads to loss of all formate-related activities. The mutation mapped near minute 17 and a single mutation was responsible for loss of both activities. A 1.4 kb DNA fragment was isolated which restored the hydrogen uptake activities and coded for a polypeptide of subunit mw 30 kDa. Dna fragments have been isolated from Chromatium vinosum and Proteus vulgaris which restored hydrogenase activities to E. coli strains with mutations in the hydA or hydB regulatory genes and which lack all hydrogenase activities. 6 refs., 12 figs.

  1. TTF1, a homeodomain containing transcription factor, contributes to regulating periodic oscillations in GnRH gene expression

    PubMed Central

    Matagne, Valerie; Kim, Jae Geun; Ryu, Byung Jun; Hur, Min Kyu; Kim, Min Sung; Kim, Kyungjin; Park, Byong Seo; Damante, Giuseppe; Smiley, Gregory; Lee, Byung Ju; Ojeda, Sergio R.

    2012-01-01

    Thyroid transcription factor 1 (TTF1), a member of the NK family of transcription factors required for basal forebrain morphogenesis, functions in the postnatal hypothalamus as a transcriptional regulator of genes encoding neuromodulators and hypophysiotrophic peptides. One of these peptides is gonadotropin-releasing hormone (GnRH). Here we show that Ttf1 mRNA abundance vary in a diurnal and melatonin-dependent fashion in the preoptic area (POA) of the rat, with maximal Ttf1 expression attained during the dark phase of the light/dark cycle, preceding the nocturnal peak in GnRH mRNA content. GnRH promoter activity oscillates in a circadian manner in GT1-7 cells, and this pattern is enhanced by TTF1 and blunted by siRNA-mediated Ttf1 gene silencing. TTF1 trans-activates GnRH transcription by binding to two sites in the GnRH promoter. Rat GnRH neurons in situ contain key proteins components of the positive (BMAL1, CLOCK) and negative (PER1) limbs of the circadian oscillator, and these proteins repress Ttf1 promoter activity in vitro. In contrast, Ttf1 transcription is activated by CRY1, a clock component required for circadian rhythmicity. In turn, TTF1 represses transcription of Rev-erbα, a heme receptor that controls circadian transcription within the positive limb of the circadian oscillator. These findings suggest that TTF1 is a component of the molecular machinery controlling circadian oscillations in GnRH gene transcription. PMID:22356123

  2. 17 CFR 240.13a-20 - Plain English presentation of specified information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Plain English presentation of specified information. 240.13a-20 Section 240.13a-20 Commodity and Securities Exchanges SECURITIES AND... Regulations Under the Securities Exchange Act of 1934 Other Reports § 240.13a-20 Plain English presentation...

  3. 17 CFR 240.13a-20 - Plain English presentation of specified information.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Plain English presentation of specified information. 240.13a-20 Section 240.13a-20 Commodity and Securities Exchanges SECURITIES AND... Regulations Under the Securities Exchange Act of 1934 Other Reports § 240.13a-20 Plain English presentation...

  4. Inflammatory abdominal aortic aneurysms. A 20-year experience.

    PubMed

    Dalainas, I; Nano, G; Ranucci, M; Bianchi, P; Stegher, S; Casana, R; Malacrida, G; Tealdi, D G

    2007-06-01

    The aim of the study was to report a 20-year single Institution experience, with the early and late outcomes of surgical treatment of inflammatory abdominal aortic aneurysms. In a 20-year period, 2 275 consecutive patients underwent elective surgical repair for non-rupture abdominal aortic aneurysm. Fifty-two patients (2.3%) were classified as inflammatory abdominal aortic aneurysms. Early and late outcomes were analyzed. One patient died in the perioperative period, giving a mortality rate of 1.92%. One patient died from a pseudoaneurysm rupture 7 months after operation. Three patients developed an aortic pseudoaneurysm in the follow-up period (mean 12.1 years, range 1-20 years) and underwent a redo operation. Overall surgical outcome of these patients, in terms of short-term and long-term is good. A high rate of pseudoaneurysm formation was observed.

  5. The Zebrafish Period2 Protein Positively Regulates the Circadian Clock through Mediation of Retinoic Acid Receptor (RAR)-related Orphan Receptor α (Rorα)*

    PubMed Central

    Wang, Mingyong; Zhong, Zhaomin; Zhong, Yingbin; Zhang, Wei; Wang, Han

    2015-01-01

    We report the characterization of a null mutant for zebrafish circadian clock gene period2 (per2) generated by transcription activator-like effector nuclease and a positive role of PER2 in vertebrate circadian regulation. Locomotor experiments showed that per2 mutant zebrafish display reduced activities under light-dark and 2-h phase delay under constant darkness, and quantitative real time PCR analyses showed up-regulation of cry1aa, cry1ba, cry1bb, and aanat2 but down-regulation of per1b, per3, and bmal1b in per2 mutant zebrafish, suggesting that Per2 is essential for the zebrafish circadian clock. Luciferase reporter assays demonstrated that Per2 represses aanat2 expression through E-box and enhances bmal1b expression through the Ror/Rev-erb response element, implicating that Per2 plays dual roles in the zebrafish circadian clock. Cell transfection and co-immunoprecipitation assays revealed that Per2 enhances bmal1b expression through binding to orphan nuclear receptor Rorα. The enhancing effect of mouse PER2 on Bmal1 transcription is also mediated by RORα even though it binds to REV-ERBα. Moreover, zebrafish Per2 also appears to have tissue-specific regulatory roles in numerous peripheral organs. These findings help define the essential functions of Per2 in the zebrafish circadian clock and in particular provide strong evidence for a positive role of PER2 in the vertebrate circadian system. PMID:25544291

  6. EphB2 signaling regulates lesion-induced axon sprouting but not critical period length in the postnatal auditory brainstem

    PubMed Central

    2013-01-01

    Background Studies of developmental plasticity may provide insight into plasticity during adulthood, when neural circuitry is less responsive to losses or changes in input. In the mammalian auditory brainstem, globular bushy cell axons of the ventral cochlear nucleus (VCN) innervate the contralateral medial nucleus of the trapezoid body (MNTB) principal neurons. VCN axonal terminations in MNTB, known as calyces of Held, are very large and specialized for high-fidelity transmission of auditory information. Following unilateral deafferentation during postnatal development, VCN axons from the intact side form connections with novel targets, including the ipsilateral MNTB. EphB signaling has been shown to play a role in this process during the first postnatal week, but mechanisms involved in this reorganization during later developmental periods remain unknown. Results We found that EphB2 signaling reduces the number of induced ipsilateral projections to the MNTB after unilateral VCN removal at postnatal day seven (P7), but not after removal of the VCN on one side at P10, after the closure of the critical period for lesion-induced innervation of the ipsilateral MNTB. Conclusions Results from this study indicate that molecular mechanisms involved in the development of circuitry may also play a part in rewiring after deafferentation during development, but do not appear to regulate the length of critical periods for plasticity. PMID:23379484

  7. Phosphorylation of the transcription activator CLOCK regulates progression through a ∼ 24-h feedback loop to influence the circadian period in Drosophila.

    PubMed

    Mahesh, Guruswamy; Jeong, EunHee; Ng, Fanny S; Liu, Yixiao; Gunawardhana, Kushan; Houl, Jerry H; Yildirim, Evrim; Amunugama, Ravi; Jones, Richard; Allen, David L; Edery, Isaac; Kim, Eun Young; Hardin, Paul E

    2014-07-11

    Circadian (≅ 24 h) clocks control daily rhythms in metabolism, physiology, and behavior in animals, plants, and microbes. In Drosophila, these clocks keep circadian time via transcriptional feedback loops in which clock-cycle (CLK-CYC) initiates transcription of period (per) and timeless (tim), accumulating levels of PER and TIM proteins feed back to inhibit CLK-CYC, and degradation of PER and TIM allows CLK-CYC to initiate the next cycle of transcription. The timing of key events in this feedback loop are controlled by, or coincide with, rhythms in PER and CLK phosphorylation, where PER and CLK phosphorylation is high during transcriptional repression. PER phosphorylation at specific sites controls its subcellular localization, activity, and stability, but comparatively little is known about the identity and function of CLK phosphorylation sites. Here we identify eight CLK phosphorylation sites via mass spectrometry and determine how phosphorylation at these sites impacts behavioral and molecular rhythms by transgenic rescue of a new Clk null mutant. Eliminating phosphorylation at four of these sites accelerates the feedback loop to shorten the circadian period, whereas loss of CLK phosphorylation at serine 859 increases CLK activity, thereby increasing PER levels and accelerating transcriptional repression. These results demonstrate that CLK phosphorylation influences the circadian period by regulating CLK activity and progression through the feedback loop. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Regulation of cAMP-induced arylalkylamine N-acetyltransferase, Period1, and MKP-1 gene expression by mitogen-activated protein kinases in the rat pineal gland.

    PubMed

    Chansard, Mathieu; Iwahana, Eiko; Liang, Jian; Fukuhara, Chiaki

    2005-10-03

    In rodent pineal glands, sympathetic innervation, which leads to norepinephrine release, is a key process in the circadian regulation of physiology and certain gene expressions. It has been shown that gene expression of the rate-limiting enzyme in the melatonin synthesis arylalkylamine N-acetyltransferase (Aa-Nat), circadian clock gene Period1, and mitogen-activated protein kinase (MAPK) phosphtase-1 (MKP-1), is controlled mainly by a norepinephrine-beta-adrenergic receptor-cAMP signaling cascade in the rat pineal gland. To further dissect the signaling cascades that regulate those gene expressions, we examined whether MAPKs are involved in cAMP-induced gene expression. Western blot and immunohistochemical analyses showed that one of the three MAPKs, c-Jun N-terminal kinase (JNK), was expressed in the pineal, and was phosphorylated by cAMP analogue stimulation with a peak 20 min after start of the stimulation, in vitro. A specific JNK inhibitor SP600125 (Anthra[1,9-cd]pyrazol-6(2H)-one1,9-pyrazoloanthrone), but not its negative control (N1-Methyl-1,9-pyrazoloanthrone), significantly reduced cAMP-stimulated Aa-Nat, Period1, and MKP-1 mRNA levels. Although another MAPK, p38(MAPK), has also been shown to be activated by cAMP stimulation, a p38(MAPK) inhibitor, SB203580 (4-(4-Fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole, HCl), showed no effect on cAMP-induced Aa-Nat and Period1 mRNA levels; whereas SB203580, but not its negative analogue SB202474 (4-Ethyl-2(p-methoxyphenyl)-5-(4'-pyridyl)-IH-imidazole, DiHCl), significantly reduced cAMP-induced MKP-1 mRNA levels. Taken together, our data suggest that cAMP-induced Aa-Nat and Period1 are likely to be mediated by activation of JNK, whereas MKP-1 may be mediated by both p38(MAPK) and JNK activations.

  9. Period1 gates the circadian modulation of memory-relevant signaling in mouse hippocampus by regulating the nuclear shuttling of the CREB kinase pP90RSK.

    PubMed

    Rawashdeh, Oliver; Jilg, Antje; Maronde, Erik; Fahrenkrug, Jan; Stehle, Jörg H

    2016-09-01

    Memory performance varies over a 24-h day/night cycle. While the detailed underlying mechanisms are yet unknown, recent evidence suggests that in the mouse hippocampus, rhythmic phosphorylation of mitogen-activated protein kinase (MAPK) and cyclic adenosine monophosphate response element-binding protein (CREB) are central to the circadian (~ 24 h) regulation of learning and memory. We recently identified the clock protein PERIOD1 (PER1) as a vehicle that translates information encoding time of day to hippocampal plasticity. We here elaborate how PER1 may gate the sensitivity of memory-relevant hippocampal signaling pathways. We found that in wild-type mice (WT), spatial learning triggers CREB phosphorylation only during the daytime, and that this effect depends on the presence of PER1. The time-of-day-dependent induction of CREB phosphorylation can be reproduced pharmacologically in acute hippocampal slices prepared from WT mice, but is absent in preparations made from Per1-knockout (Per1(-/-) ) mice. We showed that the PER1-dependent CREB phosphorylation is regulated downstream of MAPK. Stimulation of WT hippocampal neurons triggered the co-translocation of PER1 and the CREB kinase pP90RSK (pMAPK-activated ribosomal S6 kinase) into the nucleus. In hippocampal neurons from Per1(-/-) mice, however, pP90RSK remained perinuclear. A co-immunoprecipitation assay confirmed a high-affinity interaction between PER1 and pP90RSK. Knocking down endogenous PER1 in hippocampal cells inhibited adenylyl cyclase-dependent CREB activation. Taken together, the PER1-dependent modulation of cytoplasmic-to-nuclear signaling in the murine hippocampus provides a molecular explanation for how the circadian system potentially shapes a temporal framework for daytime-dependent memory performance, and adds a novel facet to the versatility of the clock gene protein PER1. We provide evidence that the circadian clock gene Period1 (Per1) regulates CREB phosphorylation in the mouse hippocampus

  10. Glutamic acid decarboxylase 65 and 67 expression in the lateral septum is up-regulated in association with the postpartum period in mice.

    PubMed

    Zhao, Changjiu; Driessen, Terri; Gammie, Stephen C

    2012-08-27

    The postpartum period in mammals undergoes a variety of physiological adaptations, including metabolic, behavioral and neuroendocrine alterations. GABA signaling has been strongly linked to various emotional states, stress responses and offspring protection. However, whether GABA signaling may change in the lateral septum (LS), a core brain region for regulating behavioral, emotional and stress responses in postpartum mice has not previously been examined. In this study, we tested whether the expression of two isoforms of glutamic acid decarboxylase (GAD), GAD65 (GAD2) and GAD67 (GAD1), the rate-limiting enzyme for GABA synthesis, exhibits altered expression in postpartum mice relative to nonmaternal, virgin mice. Using microdissected septal tissue from virgin and age-matched postpartum females, quantitative real-time PCR and Western blotting were carried out to assess GAD mRNA and protein expression, respectively. We found both protein and mRNA expression of GAD67 in the whole septum was up-regulated in postpartum mice. By contrast, no significant difference in the whole septum was observed in GAD65 expression. We then conducted a finer level of analysis using smaller microdissections and found GAD67 to be significantly increased in rostral LS, but not in caudal LS or medial septum (MS). Further, GAD65 mRNA expression in rostral LS, but not in caudal LS or MS was also significantly elevated in postpartum mice. These findings suggest that an increased GABA production in rostral LS of the postpartum mice via elevated GAD65 and GAD67 expression may contribute to multiple alterations in behavioral and emotional states, and responses to stress that occur during the postpartum period. Given that rostral LS contains GABA neurons that are projection neurons or local interneurons, it still needs to be determined whether the function of elevated GABA is for local or distant action or both.

  11. The zebrafish period2 protein positively regulates the circadian clock through mediation of retinoic acid receptor (RAR)-related orphan receptor α (Rorα).

    PubMed

    Wang, Mingyong; Zhong, Zhaomin; Zhong, Yingbin; Zhang, Wei; Wang, Han

    2015-02-13

    We report the characterization of a null mutant for zebrafish circadian clock gene period2 (per2) generated by transcription activator-like effector nuclease and a positive role of PER2 in vertebrate circadian regulation. Locomotor experiments showed that per2 mutant zebrafish display reduced activities under light-dark and 2-h phase delay under constant darkness, and quantitative real time PCR analyses showed up-regulation of cry1aa, cry1ba, cry1bb, and aanat2 but down-regulation of per1b, per3, and bmal1b in per2 mutant zebrafish, suggesting that Per2 is essential for the zebrafish circadian clock. Luciferase reporter assays demonstrated that Per2 represses aanat2 expression through E-box and enhances bmal1b expression through the Ror/Rev-erb response element, implicating that Per2 plays dual roles in the zebrafish circadian clock. Cell transfection and co-immunoprecipitation assays revealed that Per2 enhances bmal1b expression through binding to orphan nuclear receptor Rorα. The enhancing effect of mouse PER2 on Bmal1 transcription is also mediated by RORα even though it binds to REV-ERBα. Moreover, zebrafish Per2 also appears to have tissue-specific regulatory roles in numerous peripheral organs. These findings help define the essential functions of Per2 in the zebrafish circadian clock and in particular provide strong evidence for a positive role of PER2 in the vertebrate circadian system. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. The Coevolutionary Period of Wolbachia pipientis Infecting Drosophila ananassae and Its Impact on the Evolution of the Host Germline Stem Cell Regulating Genes

    PubMed Central

    Choi, Jae Young; Aquadro, Charles F.

    2014-01-01

    The endosymbiotic bacteria Wolbachia pipientis is known to infect a wide range of arthropod species yet less is known about the coevolutionary history it has with its hosts. Evidence of highly identical W. pipientis strains in evolutionary divergent hosts suggests horizontal transfer between hosts. For example, Drosophila ananassae is infected with a W. pipientis strain that is nearly identical in sequence to a strain that infects both D. simulans and D. suzukii, suggesting recent horizontal transfer among these three species. However, it is unknown whether the W. pipientis strain had recently invaded all three species or a more complex infectious dynamic underlies the horizontal transfers. Here, we have examined the coevolutionary history of D. ananassae and its resident W. pipientis to infer its period of infection. Phylogenetic analysis of D. ananassae mitochondrial DNA and W. pipientis DNA sequence diversity revealed the current W. pipientis infection is not recent. In addition, we examined the population genetics and molecular evolution of several germline stem cell (GSC) regulating genes of D. ananassae. These studies reveal significant evidence of recent and long-term positive selection at stonewall in D. ananassae, whereas pumillio showed patterns of variation consistent with only recent positive selection. Previous studies had found evidence for adaptive evolution of two key germline differentiation genes, bag of marbles (bam) and benign gonial cell neoplasm (bgcn), in D. melanogaster and D. simulans and proposed that the adaptive evolution at these two genes was driven by arms race between the host GSC and W. pipientis. However, we did not find any statistical departures from a neutral model of evolution for bam and bgcn in D. ananassae despite our new evidence that this species has been infected with W. pipientis for a period longer than the most recent infection in D. melanogaster. In the end, analyzing the GSC regulating genes individually showed two

  13. The coevolutionary period of Wolbachia pipientis infecting Drosophila ananassae and its impact on the evolution of the host germline stem cell regulating genes.

    PubMed

    Choi, Jae Young; Aquadro, Charles F

    2014-09-01

    The endosymbiotic bacteria Wolbachia pipientis is known to infect a wide range of arthropod species yet less is known about the coevolutionary history it has with its hosts. Evidence of highly identical W. pipientis strains in evolutionary divergent hosts suggests horizontal transfer between hosts. For example, Drosophila ananassae is infected with a W. pipientis strain that is nearly identical in sequence to a strain that infects both D. simulans and D. suzukii, suggesting recent horizontal transfer among these three species. However, it is unknown whether the W. pipientis strain had recently invaded all three species or a more complex infectious dynamic underlies the horizontal transfers. Here, we have examined the coevolutionary history of D. ananassae and its resident W. pipientis to infer its period of infection. Phylogenetic analysis of D. ananassae mitochondrial DNA and W. pipientis DNA sequence diversity revealed the current W. pipientis infection is not recent. In addition, we examined the population genetics and molecular evolution of several germline stem cell (GSC) regulating genes of D. ananassae. These studies reveal significant evidence of recent and long-term positive selection at stonewall in D. ananassae, whereas pumillio showed patterns of variation consistent with only recent positive selection. Previous studies had found evidence for adaptive evolution of two key germline differentiation genes, bag of marbles (bam) and benign gonial cell neoplasm (bgcn), in D. melanogaster and D. simulans and proposed that the adaptive evolution at these two genes was driven by arms race between the host GSC and W. pipientis. However, we did not find any statistical departures from a neutral model of evolution for bam and bgcn in D. ananassae despite our new evidence that this species has been infected with W. pipientis for a period longer than the most recent infection in D. melanogaster. In the end, analyzing the GSC regulating genes individually showed two

  14. Roles of A20 in autoimmune diseases.

    PubMed

    Zhang, Min; Peng, Ling-Long; Wang, Ying; Wang, Jian-Shu; Liu, Jiao; Liu, Meng-Meng; Hu, Jia; Song, Bin; Yang, Hai-Bing

    2016-04-01

    A20 (TNFAIP3), known to inhibit NF-κB function by deubiquitinating-specific NF-κB signaling molecules, has been found in many cell types of the immune system. Recent findings suggest that A20 is essential for the development and functional performance of dendritic cell, B cell, T cell and macrophage. A number of studies further demonstrate that these cells are crucial in the pathogenesis of autoimmune diseases, such as type 1 diabetes, systemic lupus erythematosus, inflammatory bowel disease, ankylosing arthritis, Sjögren's syndrome and rheumatoid arthritis. In this article, we focus on the recent advances on the roles of A20 in autoimmune diseases and discuss the therapeutic significance of these new findings.

  15. A 20 GHz Active Receive Slot Array

    NASA Technical Reports Server (NTRS)

    Tulintseff, A. N.; Lee, K.; Sukamto, L.; Chew, W.

    1994-01-01

    A 20 GHz active receive slot array has been developed for operation in the downlink frequency band of NASA's Advanced Communication Technology Satellite (ACTS) for the ACTS Mobile Terminal (AMT) project. The AMT is to demonstrate voice and data communication between a mobile terminal in Los Angeles, California, and a fixed terminal in Cleveland, Ohio, via the ACTS satellite.

  16. A 20 GHz Active Receive Slot Array

    NASA Technical Reports Server (NTRS)

    Tulintseff, A. N.; Lee, K.; Sukamto, L.; Chew, W.

    1994-01-01

    A 20 GHz active receive slot array has been developed for operation in the downlink frequency band of NASA's Advanced Communication Technology Satellite (ACTS) for the ACTS Mobile Terminal (AMT) project. The AMT is to demonstrate voice and data communication between a mobile terminal in Los Angeles, California, and a fixed terminal in Cleveland, Ohio, via the ACTS satellite.

  17. Hippocampal cell fate regulation by chronic cocaine during periods of adolescent vulnerability: Consequences of cocaine exposure during adolescence on behavioral despair in adulthood.

    PubMed

    García-Cabrerizo, R; Keller, B; García-Fuster, M J

    2015-09-24

    Given that adolescence represents a critical moment for shaping adult behavior and may predispose to disease vulnerability later in life, the aim of this study was to find a vulnerable period during adolescence in which hippocampal cell fate regulation was altered by cocaine exposure, and to evaluate the long-term consequences of a cocaine experience during adolescence in affecting hippocampal plasticity and behavioral despair in adulthood. Study I: Male rats were treated with cocaine (15mg/kg, i.p.) or saline for 7 consecutive days during adolescence (early post-natal day (PND) 33-39, mid PND 40-46, late PND 47-53). Hippocampal plasticity (i.e., cell fate regulation, cell genesis) was evaluated 24h after the last treatment dose during the course of adolescence (PND 40, PND 47, PND 54). Study II: The consequences of cocaine exposure during adolescence (PND 33-39 or PND 33-46; 7 or 14days) were measured in adulthood at the behavioral (i.e., forced swim test, PND 62-63) and molecular (hippocampal cell markers, PND 64) levels. Chronic cocaine during early adolescence dysregulated FADD forms only in the hippocampus (HC), as compared to other brain regions, and during mid adolescence, impaired cell proliferation (Ki-67) and increased PARP-1 cleavage (a cell death maker) in the HC. Interestingly, chronic cocaine exposure during adolescence did not alter the time adult rats spent immobile in the forced swim test. These results suggest that this paradigm of chronic cocaine administration during adolescence did not contribute to the later manifestation of behavioral despair (i.e., one pro-depressive symptom) as measured by the forced swim test in adulthood. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Analysis of a lin-42/period Null Allele Implicates All Three Isoforms in Regulation of Caenorhabditis elegans Molting and Developmental Timing.

    PubMed

    Edelman, Theresa L B; McCulloch, Katherine A; Barr, Angela; Frøkjær-Jensen, Christian; Jorgensen, Erik M; Rougvie, Ann E

    2016-12-07

    The Caenorhabditis elegans heterochronic gene pathway regulates the relative timing of events during postembryonic development. lin-42, the worm homolog of the circadian clock gene, period, is a critical element of this pathway. lin-42 function has been defined by a set of hypomorphic alleles that cause precocious phenotypes, in which later developmental events, such as the terminal differentiation of hypodermal cells, occur too early. A subset of alleles also reveals a significant role for lin-42 in molting; larval stages are lengthened and ecdysis often fails in these mutant animals. lin-42 is a complex locus, encoding overlapping and nonoverlapping isoforms. Although existing alleles that affect subsets of isoforms have illuminated important and distinct roles for this gene in developmental timing, molting, and the decision to enter the alternative dauer state, it is essential to have a null allele to understand all of the roles of lin-42 and its individual isoforms. To remedy this problem and discover the null phenotype, we engineered an allele that deletes the entire lin-42 protein-coding region. lin-42 null mutants are homozygously viable, but have more severe phenotypes than observed in previously characterized hypomorphic alleles. We also provide additional evidence for this conclusion by using the null allele as a base for reintroducing different isoforms, showing that each isoform can provide heterochronic and molting pathway activities. Transcript levels of the nonoverlapping isoforms appear to be under coordinate temporal regulation, despite being driven by independent promoters. The lin-42 null allele will continue to be an important tool for dissecting the functions of lin-42 in molting and developmental timing.

  19. A critical size and period hypothesis to explain natural regulation of salmon abundance and the linkage to climate and climate change

    NASA Astrophysics Data System (ADS)

    Beamish, R. J.; Mahnken, Conrad

    We hypothesise that salmon year class strength is determined in two stages during the first year in the ocean. There is an early natural mortality that is mostly related to predation, which is followed by a physiologically-based mortality. Juvenile salmon that fail to reach a critical size by the end of their first marine summer do not survive the following winter. In this study we describe our initial tests of this critical size and critical period hypothesis using data from ocean surveys of juvenile salmon and from experimental feeding studies on coho. Conservative swept volume abundance estimates for juvenile coho, and possibly chinook, indicate that there is high mortality in fall and winter during their first year in the sea. Studies of otolith weight show that the length and otolith-weight relationship for young coho changes in the early fall of their first ocean year. Studies of growth and associated hormone levels in feeding studies show that slow growing juvenile coho are stunted and deficient in an insulin-like growth factor-I (IGF-I). Juvenile coho sampled in September had low IGF-I values, indicative of poor growth. The results of these studies provide evidence for the general hypothesis that growth-related mortality occurs late in the first marine year and may be important in determining the strength of the year class (brood year). The link between total mortality and climate could be operating via the availability of nutrients regulating the food supply and hence competition for food (i.e. bottom-up regulation).

  20. Analysis of a lin-42/period Null Allele Implicates All Three Isoforms in Regulation of Caenorhabditis elegans Molting and Developmental Timing

    PubMed Central

    Edelman, Theresa L. B.; McCulloch, Katherine A.; Barr, Angela; Frøkjær-Jensen, Christian; Jorgensen, Erik M.; Rougvie, Ann E.

    2016-01-01

    The Caenorhabditis elegans heterochronic gene pathway regulates the relative timing of events during postembryonic development. lin-42, the worm homolog of the circadian clock gene, period, is a critical element of this pathway. lin-42 function has been defined by a set of hypomorphic alleles that cause precocious phenotypes, in which later developmental events, such as the terminal differentiation of hypodermal cells, occur too early. A subset of alleles also reveals a significant role for lin-42 in molting; larval stages are lengthened and ecdysis often fails in these mutant animals. lin-42 is a complex locus, encoding overlapping and nonoverlapping isoforms. Although existing alleles that affect subsets of isoforms have illuminated important and distinct roles for this gene in developmental timing, molting, and the decision to enter the alternative dauer state, it is essential to have a null allele to understand all of the roles of lin-42 and its individual isoforms. To remedy this problem and discover the null phenotype, we engineered an allele that deletes the entire lin-42 protein-coding region. lin-42 null mutants are homozygously viable, but have more severe phenotypes than observed in previously characterized hypomorphic alleles. We also provide additional evidence for this conclusion by using the null allele as a base for reintroducing different isoforms, showing that each isoform can provide heterochronic and molting pathway activities. Transcript levels of the nonoverlapping isoforms appear to be under coordinate temporal regulation, despite being driven by independent promoters. The lin-42 null allele will continue to be an important tool for dissecting the functions of lin-42 in molting and developmental timing. PMID:27729432

  1. Spatiotemporal expression and transcriptional regulation of heme oxygenase and biliverdin reductase genes in zebrafish (Danio rerio) suggest novel roles during early developmental periods of heightened oxidative stress.

    PubMed

    Holowiecki, Andrew; O'Shields, Britton; Jenny, Matthew J

    2017-01-01

    Heme oxygenase 1 (HMOX1) degrades heme into biliverdin, which is subsequently converted to bilirubin by biliverdin reductase (BVRa or BVRb) in a manner analogous to the classic anti-oxidant glutathione-recycling pathway. To gain a better understanding of the potential antioxidant roles the BVR enzymes may play during development, the spatiotemporal expression and transcriptional regulation of zebrafish hmox1a, bvra and bvrb were characterized under basal conditions and in response to pro-oxidant exposure. All three genes displayed spatiotemporal expression patterns consistent with classic hematopoietic progenitors during development. Transient knockdown of Nrf2a did not attenuate the ability to detect bvra or bvrb by ISH, or alter spatial expression patterns in response to cadmium exposure. While hmox1a:mCherry fluorescence was documented within the intermediate cell mass, a transient location of primitive erythrocyte differentiation, expression was not fully attenuated in Nrf2a morphants, but real-time RT-PCR demonstrated a significant reduction in hmox1a expression. Furthermore, Gata-1 knockdown did not attenuate hmox1a:mCherry fluorescence. However, while there was a complete loss of detection of bvrb expression by ISH at 24hpf, bvra expression was greatly attenuated but still detectable in Gata-1 morphants. In contrast, 96 hpf Gata-1 morphants displayed increased bvra and bvrb expression within hematopoietic tissues. Finally, temporal expression patterns of enzymes involved in the generation and maintenance of NADPH were consistent with known changes in the cellular redox state during early zebrafish development. Together, these data suggest that Gata-1 and Nrf2a play differential roles in regulating the heme degradation enzymes during an early developmental period of heightened cellular stress. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. The inhibitory effect of A20 on the inflammatory reaction of epidermal keratinocytes.

    PubMed

    Sohn, Kyung-Cheol; Back, Seung Ju; Choi, Dae-Kyoung; Shin, Jung-Min; Kim, Sue Jeong; Im, Myung; Lee, Young; Seo, Young-Joon; Yoon, Tae-Jin; Lee, Young Ho; Lee, Jeung-Hoon; Kim, Chang Deok

    2016-04-01

    A20 is a negative regulator of nuclear factor κ-light‑chain-enhancer of activated B cells (NF-κB) signaling, and has been implicated in the pathogenesis of psoriasis through genome-wide association study (GWAS). In the present study, we investigated the putative role of A20 in epidermal keratinocytes. Immunohistochemical analysis showed that A20 was expressed in all layers of the epidermis, with an increasing pattern in the upper layers. In our model of calcium-induced keratinocyte differentiation, A20 expression was increased in a time-dependent manner. To investigate whether A20 affected keratinocyte differentiation, we overexpressed A20 in cultured keratinocytes. As a result, we noted that A20 overexpression did not affect keratinocyte differentiation, suggesting that A20 is not a direct modulator of keratinocyte differentiation. Interestingly, we found that A20 levels were decreased in psoriatic lesional skin compared to non-lesional areas. To investigate whether A20 played a role in the innate immune response of keratinocytes, we overexpressed A20 and then examined poly(I:C)-induced cytokine expression. We noted that A20 significantly inhibited poly(I:C)-induced cytokine production, and this effect was related to the inhibition of NF-κB signaling. These results suggest that the downregulation of A20 increased the susceptibility of keratinocytes to external stimuli, thus contributing to the development of psoriasis.

  3. Regulation of the G1 phase of the cell cycle by periodic stabilization and degradation of the p25rum1 CDK inhibitor.

    PubMed Central

    Benito, J; Martín-Castellanos, C; Moreno, S

    1998-01-01

    In fission yeast, the cyclin-dependent kinase (CDK) inhibitor p25(rum1) is a key regulator of progression through the G1 phase of the cell cycle. We show here that p25(rum1) protein levels are sharply periodic. p25(rum1) begins to accumulate at anaphase, persists in G1 and is destroyed during S phase. p25(rum1 )is stabilized and polyubiquitinated in a mutant defective in the 26S proteasome, suggesting that its degradation normally occurs through the ubiquitin-dependent 26S proteasome pathway. Phosphorylation of p25(rum1 )by cdc2-cyclin complexes at residues T58 and T62 is important to target the protein for degradation. Mutation of one or both of these residues to alanine causes stabilization of p25(rum1) and induces a cell cycle delay in G1 and polyploidization due to occasional re-initiation of DNA replication before mitosis. The CDK-cyclin complex cdc2-cig1, which is insensitive to p25(rum1 )inhibition, seems to be the main kinase that phosphorylates p25(rum1). Phosphorylation of p25(rum1) in S phase and G2 serves as the trigger for p25(rum1) proteolysis. Thus, periodic accumulation and degradation of the CDK inhibitor p25(rum1 )in G1 plays a role in setting a threshold of cyclin levels important in determining the length of the pre-Start G1 phase and in ensuring the correct order of cell cycle events. PMID:9430640

  4. Down-regulation of Kir2.6 channel by c-termini mutation D252N and its association with the susceptibility to Thyrotoxic Periodic Paralysis.

    PubMed

    Paninka, Rolf Matias; Carlos-Lima, Estevão; Lindsey, Susan C; Kunii, Ilda S; Dias-da-Silva, Magnus R; Arcisio-Miranda, Manoel

    2017-03-27

    Inward rectifying potassium - Kir - channels drive the resting potential to potassium reversal potential and, when disrupted, might be related to muscular diseases. Recently, Thyrotoxic Periodic Paralysis (TPP) has emerged as a channelopathy related to mutations in KCNJ18 gene, which encodes Kir2.6 channel. TPP is a neuromuscular disorder characterized by a triad of muscle weakness, hypokalemia, and thyrotoxicosis, the latter being essential for the crisis. Direct sequencing revealed two heterozygous mutations - D252N and R386C - in two TPP patients. KCNJ18 cDNAs were cloned into mammalian expression plasmids and transiently expressed in HEK 293T cells to investigate the functional effects of Kir2.6 mutations. Patch-clamp and confocal laser scanning microscopy experiments were carried out, comparing the WT channel to its mutants. D252N mutation down-regulates the Kir2.6 activity, decreasing the K(+) current density (∼34%) when compared to the WT channel; whereas the mutation R386C shows no significant changes from WT. The mutant D252N Kir2.6 channel also showed a substantial reduction of ∼51% in membrane abundance relative to WT channel. Our study describes the functional consequences of a single amino acid change in Kir2.6 channel. Further analysis regarding hormonal conditions and Kir channel expression are required to provide new clues about the TPP pathophysiology.

  5. 17 CFR 240.14a-20 - Shareholder approval of executive compensation of TARP recipients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Shareholder approval of executive compensation of TARP recipients. 240.14a-20 Section 240.14a-20 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF...

  6. Policies of price regulators in periods of high or increasing costs and their potential long-term effect on investment: The case of the electric utility industry in the 1970s and 1980s

    NASA Astrophysics Data System (ADS)

    Hardarson, Pall

    This study presents and estimates a model of electric utility regulation during periods of high or rising costs. Regulators are viewed as utility maximizers, whose utility function is influenced by political pressure from consumers and the regulated firms. The model can also be interpreted as a reduced form bargaining model. Although regulators have frequently been modeled in the theoretical literature on regulation as having a well defined utility function, this is, to my knowledge, the first empirical study of electric utility regulation that takes this approach. This study also uses a far larger data set than previous studies on electric utility regulation. It is found that policies like those carried out by price regulators during the 1970s and 1980s can potentially lead to serious underinvestment. This underinvestment result applies to all states in my sample. The underinvestment bias, however, is likely to be mitigated if high cost periods are short in duration. Based on the estimation results of this study, states are ranked according to the regulatory climate for the regulated firms. Regulatory policies between states differed significantly. Policies like those in states with the least favorable regulatory climate appear likely to frequently jeopardize utilities' financial position during high cost periods, whereas policies in states with average to good regulatory climate (relative to my sample) are much less likely to do so. This study also examines the effect on regulatory policies of a few political variables commonly included in studies of electric utility regulators. The effect of these variables is found to be negligible. This result, as well as the underinvestment result and the ranking of states according to regulatory climate, is in general agreement with previous empirical work.

  7. Intranasal and transantral ethmoidectomy: a 20-year experience.

    PubMed

    Friedman, W H; Katsantonis, G P

    1990-04-01

    Ethmoidectomy is an operation that has engendered controversy concerning the best route of surgical access. The purpose of this study was to present the results of the authors' experience in more than 1300 intranasal sphenoethmoidectomies and transantral sphenoethmoidectomies performed over a 20-year period. The authors contend that the most effective ethmoidectomy is the most complete ethmoidectomy and have previously presented a case for ethmoid marsupialization. Polyp recurrence rates of less than 20% and a major complication rate of less than 1% were reported in this study.

  8. A 20mK temperature sensor

    SciTech Connect

    Wang, N.; Sadoulet, B.; Shutt, T.; Beeman, J.; Haller, E.E.; Lange, A.; Park, I.; Ross, R.; Stanton, C.; Steiner, H.

    1987-11-01

    We are developing a 20mK temperature sensor made of neutron transmutation doped (NTD) germanium for use as a phonon detector in a dark matter search. We find that NTD germanium thermistors around 20mK have resistances which are a strong function of temperature, and have sufficient sensitivity to eventually reach a base line rms energy fluctuation of 6eV at 25mK. Further work is needed to understand the extreme sensitivity of the thermistors to bias power. 13 refs., 18 figs.

  9. Period Cramps

    MedlinePlus

    ... Getting Your Period at School Do Periods Ever End? When Will I Get My Period? ... Nondiscrimination Visit the Nemours Web site. Note: All information on KidsHealth® is for educational purposes ...

  10. Effects of regulated deficit irrigation during the pre-harvest period on gas exchange, leaf development and crop yield of mature almond trees.

    PubMed

    Romero, Pascual; Navarro, Josefa Maria; García, Francisco; Botía Ordaz, Pablo

    2004-03-01

    We investigated the effects of regulated deficit irrigation (RDI) during the pre-harvest period (kernel-filling stage) on water relations, leaf development and crop yield in mature almond (Prunus dulcis (Mill.) D.A. Webb cv. Cartagenera) trees during a 2-year field experiment. Trees were either irrigated at full-crop evapotranspiration (ETc=100%) (well-irrigated control treatment) or subjected to an RDI treatment that consisted of full irrigation for the full season, except from early June to early August (kernel-filling stage), when 20% ETc was applied. The severity of water stress was characterized by measurements of soil water content, predawn leaf water potential (Psipd) and relative water content (RWC). Stomatal conductance (gs), net CO2 assimilation rate (A), transpiration rate (E), leaf abscission, leaf expansion rate and crop yield were also measured. In both years, Psipd and RWC of well-irrigated trees were maintained above -1.0 MPa and 92%, respectively, whereas the corresponding values for trees in the RDI treatment were -2.37 MPa and 82%. Long-term water stress led to a progressive decline in gs, A and E, with significant reductions after 21 days in the RDI treatment. At the time of maximum stress (48 days after commencement of RDI), A, gs and E were 64, 67 and 56% lower than control values, respectively. High correlations between A, E and gs were observed. Plant water status recovered within 15 days after the resumption of irrigation and was associated with recovery of soil water content. A relatively rapid and complete recovery of A and gs was also observed, although the recovery was slower than for Psipd and RWC. Severe water stress during the kernel-filling stage resulted in premature defoliation (caused by increased leaf abscission) and a reduction in leaf growth rate, which decreased tree leaf area. Although kernel yield was correlated with leaf water potential, RDI caused a nonsignificant 7% reduction in kernel yield and had no effect on kernel

  11. Irregular Periods

    MedlinePlus

    ... number of days after the last one. The Menstrual Cycle Most girls get their first period between the ... to skip periods or to have an irregular menstrual cycle. Illness, rapid weight change, or stress can also ...

  12. Description of a 20 Kilohertz power distribution system

    NASA Technical Reports Server (NTRS)

    Hansen, I. G.

    1986-01-01

    A single phase, 440 VRMS, 20 kHz power distribution system with a regulated sinusoidal wave form is discussed. A single phase power system minimizes the wiring, sensing, and control complexities required in a multi-sourced redundantly distributed power system. The single phase addresses only the distribution link; mulitphase lower frequency inputs and outputs accommodation techniques are described. While the 440 V operating potential was initially selected for aircraft operating below 50,000 ft, this potential also appears suitable for space power systems. This voltage choice recognizes a reasonable upper limit for semiconductor ratings, yet will direct synthesis of 220 V, 3 power. A 20 kHz operating frequency was selected to be above the range of audibility, minimize the weight of reactive components, yet allow the construction of single power stages of 25 to 30 kW. The regulated sinusoidal distribution system has several advantages. With a regulated voltage, most ac/dc conversions involve rather simple transformer rectifier applications. A sinusoidal distribution system, when used in conjunction with zero crossing switching, represents a minimal source of EMI. The present state of 20 kHz power technology includes computer controls of voltage and/or frequency, low inductance cable, current limiting circuit protection, bi-directional power flow, and motor/generator operating using standard induction machines. A status update and description of each of these items and their significance is presented.

  13. Persistence in periodic and almost periodic Lotka-Volterra systems.

    PubMed

    Gopalsamy, K

    1984-01-01

    It is shown that a strongly self-regulating (or resource limited) Lotka-Volterra population system can "persist" in a periodic or almost periodic environment if and only if the system tracks the environmental variations.

  14. A20 inhibits the motility of HCC cells induced by TNF-α.

    PubMed

    Wang, Xianteng; Ma, Chao; Zong, Zhaoyun; Xiao, Ying; Li, Na; Guo, Chun; Zhang, Lining; Shi, Yongyu

    2016-03-22

    Metastasis of hepatocellular carcinoma (HCC) can be facilitated by TNF-α, a prototypical inflammatory cytokine in the HCC microenvironment. A20 is a negative regulator of NF-κB signaling pathway. In the present study we ask whether A20 plays a role in HCC metastasis. We found that A20 expression was downregulated in the invasive cells of microvascular invasions (MVI) compared with the noninvasive cells in 89 tissue samples from patients with HCC by immunochemistry methods. Overexpression of A20 in HCC cell lines inhibited their motility induced by TNF-α. Furthermore, the overexpression of A20 inhibited epithelial-mesenchymal transition (EMT), FAK activation and RAC1 activity. By contrast, knockdown of A20 in one HCC cell line results in the converse. In addition, the overexpression of A20 restrained the formation of MVI in HCC xenograft in nude mice treated with TNF-α. All the results suggested that A20 functioned as a negative regulator in motility of HCC cells induced by TNF-α.

  15. Hormonal changes during a 20-week confinement.

    PubMed

    Maillet, A; Titze, J; Gushin, V; Nichiporuk, I; Kirsch, K A; Gharib, C; Gauquelin-Koch, G

    1998-11-01

    When the European Space Agency planned the EUROMIR'95 long-duration flight with a European astronaut on board the Russian orbital MIR station, it organized simultaneously a ground simulation, called the Human Behaviour Study, of this manned space mission. The ground simulation was a confinement experiment, and this paper describes the changes in volume-regulating hormones that occurred during and after 20 weeks of confinement. In a normobaric diving chamber, 3 subjects were confined for 135 d. Arterial pressure, plasma concentrations of blood volume-regulating hormones (active renin and arginine-vasopressin), and urinary variables (aldosterone, arginine-vasopressin, and metabolites of catecholamines) were measured before, during, and after confinement. Arterial pressure was increased from week 1 until week 15 of confinement, while heart rate was elevated from week 6 until the end of the simulation. Plasma active renin was elevated throughout the confinement (after week 6). Urine volume increased transitively on the first 2 d of confinement. The results obtained during this long-term confinement experiment have major importance regarding concerns about spaceflight and bed rest data, because we observed hormonal changes during the experiment that normally are assigned to the fluid shift that occurs in weightlessness or in the head-down tilt position (i.e., an increase of renin, an increase of urinary volume during the first two days, and a decreased urinary cyclic guanosine monophosphate.

  16. A20 Attenuates FFAs-induced Lipid Accumulation in Nonalcoholic Steatohepatitis

    PubMed Central

    Ai, Luoyan; Xu, Qingqing; Wu, Changwei; Wang, Xiaohan; Chen, Zhiwei; Su, Dazhi; Jiang, Xiaoke; Xu, Antao; Lin, Qing; Fan, Zhuping

    2015-01-01

    A20 is a ubiquitin-editing enzyme that attenuates the activity of proximal signaling complexes at pro-inflammatory receptors. It has been well documented that A20 protein plays an important role in response to liver injury and hepatocytes apoptosis in pro-inflammatory pathways. However, there was little evidence showing that A20 protein was involving in fatty-acid homeostasis except the up-regulation of two fatty acid metabolism regulatory genes at mRNA level (PPARa and CPT1a) by adenovirus-mediated A20 protein overexpression. In this study we found that: 1) the expression level of A20 protein was significantly higher in the steatotic liver from MCD-fed mice than the controls; 2) Overexpression of A20 protein suppressed FFAs-stimulated triglyceride deposition in HepG2 cells while under expression of A20 protein increased FFAs-stimulated triglyceride deposition; 3) Overexpression of A20 protein in HepG2 cells upregulated genes that promote β-oxidation and decreased the mRNA levels of key lipogenic genes such as fatty acid synthase (FAS), indicating A20 function as anti-steatotic factor by the activation of mitochondrial β-oxidation and attenuation of de novo lipogenesis; 4) Nonalcoholic steatohepatitis (NASH) patients showed significantly higher A20 expression level in liver compared with control individuals. Our results demonstrated that A20 protein plays an important role in fatty-acid homeostasis in human as well as animals. In addition, our data suggested that the pathological function of A20 protein in hepatocyte from lipotoxicity to NASH is by the alleviation of triglyceride accumulation in hepatocytes. Elevated expression of A20 protein could be a potential therapeutic strategy for preventing the progression of nonalcoholic steatohepatitis. PMID:26681923

  17. A20 deletion in T cells modulates acute graft-versus-host disease in mice.

    PubMed

    Fischer, Julius C; Otten, Vera; Steiger, Katja; Schmickl, Martina; Slotta-Huspenina, Julia; Beyaert, Rudi; van Loo, Geert; Peschel, Christian; Poeck, Hendrik; Haas, Tobias; Spoerl, Silvia

    2017-08-22

    The NF-κB regulator A20 limits inflammation by providing negative feedback in myeloid cells and B cells. Functional lack of A20 has been linked to several inflammatory and autoimmune diseases. To define how A20 affects the functionality of T effector cells in a highly inflammatory environment, we performed conventional allogeneic hematopoietic stem cell transplantation (allo-HSCT) with A20-deficient CD4(+) and CD8(+) donor T cells in mice. Severity and mortality of graft-versus-host disease (GVHD) after allo-HSCT was drastically reduced in recipients transplanted with conventional doses of A20-deficient T cells. Consistently, we found that the A20-deficient donor T cell compartment was strongly diminished at various timepoints after allo-HSCT. However, proportionally more A20-deficient donor T cells produced IFN-γ and systemic inflammation was elevated early after allo-HSCT. Consequently, increasing the dose of transplanted A20-deficient T cells reversed the original phenotype and resulted in enhanced GVHD mortality compared to recipients that received A20(+/+) T cells. Still, A20-deficient T cells, activated either through T cell receptor-dependent or -independent mechanisms, were less viable than control A20(+/+) T cells, highlighting that A20 balances both, T cell activation and survival. Thus, our findings suggest that targeting A20 in T cells may allow to modulate T cell mediated inflammatory diseases like GVHD. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  18. Bibliometric analysis of global environmental assessment research in a 20-year period

    SciTech Connect

    Li, Wei Zhao, Yang

    2015-01-15

    Based on the samples of 113,468 publications on environmental assessment (EA) from the past 20 years, we used a bibliometric analysis to study the literature in terms of trends of growth, subject categories and journals, international collaboration, geographic distribution of publications, and scientific research issues. By applying thresholds to network centralities, a core group of countries can be distinguished as part of the international collaboration network. A frequently used keywords analysis found that the priority in assessment would gradually change from project environmental impact assessment (EIA) to strategic environmental assessment (SEA). Decision-theoretic approaches (i.e., environmental indicator selection, life cycle assessment, etc.), along with new technologies and methods (i.e., the geographic information system and modeling) have been widely applied in the EA research field over the past 20 years. Hot spots such as “biodiversity” and “climate change” have been emphasized in current EA research, a trend that will likely continue in the future. The h-index has been used to evaluate the research quality among countries all over the world, while the improvement of developing countries' EA systems is becoming a popular research topic. Our study reveals patterns in scientific outputs and academic collaborations and serves as an alternative and innovative way of revealing global research trends in the EA research field.

  19. Surgical removal of intra-abdominal intrauterine devices at one center in a 20-year period.

    PubMed

    Ertopcu, Kenan; Nayki, Cenk; Ulug, Pasa; Nayki, Umit; Gultekin, Emre; Donmez, Aysegul; Yildirim, Yusuf

    2015-01-01

    To review 20 years of experience of the removal of intra-abdominal intrauterine devices (IUDs) and to compare the surgical methods used. In a retrospective study, charts dating from between September 1, 1992, and August 31, 2012, were reviewed. Patients were eligible for inclusion when they had an IUD surgically removed by minilaparotomy or laparoscopy at a tertiary referral center in Izmir, Turkey. Among the 36 eligible women, 18 (50%) had undergone laparoscopy and 18 (50%) had undergone minilaparotomy. Mean operation length was 55.3±6.3 minutes in the laparoscopy group and 29.1±4.2 minutes in the minilaparotomy group (P=0.008). Conversion to full laparotomy was necessary in 4 (22%) women in the laparoscopy group and 1 (6%) in the minilaparotomy group (P=0.02). Perioperative complications were observed in 5 (14%) women, with no difference in frequency between groups (P=0.09). Total cost of medical/surgical procedures was US$436.4±35.4 for the laparoscopy group and $323.4±21.3 for the minilaparotomy group (P=0.04). Minilaparotomy seems to be an important alternative to laparoscopy for the removal of intra-abdominal IUDs. This procedure should be an integral part of gynecologic surgical training. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  20. Experience in cochlear reimplantation. Descriptive study of a 20-year period.

    PubMed

    Gutiérrez-Salazar, Andrés; Cop, Constanze; Osorio-Acosta, Ángel; Borkoski-Barreiro, Silvia; Falcón-González, Juan C; Ramos-Macías, Ángel

    2015-01-01

    The cochlear implant is a surgical procedure that has increased substantially, because the paediatric population is diagnosed and implanted early and because there are increased potential indications. This device has the inherent risk of failure in performance, as dies any active medical device, which is the most common cause of implant removal. Our goal was to understand what the causes that produced removal in our series were, and confirm if these conformed to reality as reviewed in the literature. This was a retrospective, descriptive, observational study of 859 cochlear implant surgeries carried out between October 1991 and May 2011. The causes of implant removal were classified according to the European Consensus Statement on Cochlear Implant Failures and Explantations. The reimplantation rate was 6.16% (n=51). The most common reason for removal was technical device failure (45.5%), followed by infection/rejection (23.6%) and upgrade (12.7%). Less common causes: there were 3 cases (5.6%) of electrode misplacement, 2 cases (3.6%) of labyrinthine ossification, 2 (3.6%) as a result of head trauma, 2 (3.6%) from need for nuclear magnetic resonance imaging and 1 case (1.8%) from psychiatric illness. Cochlear reimplantation is a safe procedure, with a low complication rate. In our centre, it reaches an overall rate of 6.16%. Technical device failure remains the most common cause of this procedure, although there is a significant percentage of reimplantation for device update. Copyright © 2014 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial. All rights reserved.

  1. A20 prevents chronic liver inflammation and cancer by protecting hepatocytes from death

    PubMed Central

    Catrysse, L; Farhang Ghahremani, M; Vereecke, L; Youssef, S A; Mc Guire, C; Sze, M; Weber, A; Heikenwalder, M; de Bruin, A; Beyaert, R; van Loo, G

    2016-01-01

    An important regulator of inflammatory signalling is the ubiquitin-editing protein A20 that acts as a break on nuclear factor-κB (NF-κB) activation, but also exerts important cytoprotective functions. A20 knockout mice are cachectic and die prematurely due to excessive multi-organ inflammation. To establish the importance of A20 in liver homeostasis and pathology, we developed a novel mouse line lacking A20 specifically in liver parenchymal cells. These mice spontaneously develop chronic liver inflammation but no fibrosis or hepatocellular carcinomas, illustrating an important role for A20 in normal liver tissue homeostasis. Hepatocyte-specific A20 knockout mice show sustained NF-κB-dependent gene expression in the liver upon tumor necrosis factor (TNF) or lipopolysaccharide injection, as well as hepatocyte apoptosis and lethality upon challenge with sublethal doses of TNF, demonstrating an essential role for A20 in the protection of mice against acute liver failure. Finally, chronic liver inflammation and enhanced hepatocyte apoptosis in hepatocyte-specific A20 knockout mice was associated with increased susceptibility to chemically or high fat-diet-induced hepatocellular carcinoma development. Together, these studies establish A20 as a crucial hepatoprotective factor. PMID:27253414

  2. Testing the Disk Regulation Paradigm with Spitzer Observations. I. Rotation Periods of Pre-Main-Sequence Stars in the IC 348 Cluster

    NASA Astrophysics Data System (ADS)

    Cieza, Lucas; Baliber, Nairn

    2006-10-01

    We present 105 stellar rotation periods in the young cluster IC 348, 75 of which are new detections, increasing the total number of known periods in this cluster to 143. The period distribution resembles that seen in the heart of the Orion Nebula cluster by Herbst and colleagues. Stars estimated to be less massive than 0.25 Msolar show a unimodal distribution of fast rotators (P~1-2 days) and a tail of slower rotators, while stars estimated to be more massive than 0.25 Msolar show a bimodal distribution with peaks at ~2 and ~8 days. We combine all published rotation periods in IC 348 with Spitzer mid-IR (3.6, 4.5, 5.8, and 8.0 μm) photometry, an unprecedentedly efficient and reliable disk indicator, in order to test the disk-braking paradigm. We find no evidence that the tail of slow rotators in low-mass stars or the long-period peak in high-mass stars are preferentially populated by objects with disks as might be expected based on the current disk-braking model. We find some indication that the disk fraction decreases significantly for stars with very short periods (P<~1.5 days), which is the only feature of our sample that could potentially be interpreted as evidence for disk braking. It has been proposed that the observational signatures of disk braking might be significantly masked by the intrinsic breadth of the initial period distribution. We argue that more rigorous modeling of angular momentum evolution and a quantitative analysis of the observational data are required before the disk-braking model can be regarded as inconsistent with observations.

  3. A20 Deficiency in Lung Epithelial Cells Protects against Influenza A Virus Infection

    PubMed Central

    Vereecke, Lars; Mc Guire, Conor; Sze, Mozes; Schuijs, Martijn J.; Willart, Monique; Itati Ibañez, Lorena; Hammad, Hamida; Lambrecht, Bart N.; Beyaert, Rudi; Saelens, Xavier; van Loo, Geert

    2016-01-01

    A20 negatively regulates multiple inflammatory signalling pathways. We here addressed the role of A20 in club cells (also known as Clara cells) of the bronchial epithelium in their response to influenza A virus infection. Club cells provide a niche for influenza virus replication, but little is known about the functions of these cells in antiviral immunity. Using airway epithelial cell-specific A20 knockout (A20AEC-KO) mice, we show that A20 in club cells critically controls innate immune responses upon TNF or double stranded RNA stimulation. Surprisingly, A20AEC-KO mice are better protected against influenza A virus challenge than their wild type littermates. This phenotype is not due to decreased viral replication. Instead host innate and adaptive immune responses and lung damage are reduced in A20AEC-KO mice. These attenuated responses correlate with a dampened cytotoxic T cell (CTL) response at later stages during infection, indicating that A20AEC-KO mice are better equipped to tolerate Influenza A virus infection. Expression of the chemokine CCL2 (also named MCP-1) is particularly suppressed in the lungs of A20AEC-KO mice during later stages of infection. When A20AEC-KO mice were treated with recombinant CCL2 the protective effect was abrogated demonstrating the crucial contribution of this chemokine to the protection of A20AEC-KO mice to Influenza A virus infection. Taken together, we propose a mechanism of action by which A20 expression in club cells controls inflammation and antiviral CTL responses in response to influenza virus infection. PMID:26815999

  4. Cleavage by MALT1 induces cytosolic release of A20.

    PubMed

    Malinverni, Claire; Unterreiner, Adeline; Staal, Jens; Demeyer, Annelies; Galaup, Marion; Luyten, Marcel; Beyaert, Rudi; Bornancin, Frédéric

    2010-10-01

    The MALT1 paracaspase has arginine-directed proteolytic activity. A20 is a dual ubiquitin-editing enzyme involved in termination of NF-κB signaling. Upon T- or B-cell receptor engagement human (h) A20 is cleaved by MALT1 after arginine 439, yielding an N-terminal fragment (hA20p50) and a C-terminal one (hA20p37). The hA20p50 fragment has never been detected directly, thus limiting insight into the functional consequences of MALT1-mediated cleavage of A20. Here, various antibodies were tested, including newly generated hA20p50 and hA20p37 specific antibodies, leading to detection of the hA20p50 fragment produced after MALT1-mediated cleavage of ectopically expressed as well as endogenous A20 proteins. The properties of both A20 fragments, generated upon co-expression with a constitutively active MALT1 protein, were further studied by sub-cellular fractionation and fluorescence microscopy. In contrast to full-length A20 which is particulate and insoluble, we found hA20p50 to be soluble and readily released into the cytosol whereas hA20p37 was partially soluble, thus suggesting loss of compartmentalization as a possible mechanism for MALT1-mediated dampening of A20 function.

  5. Tumor Suppressor A20 Protects against Cardiac Hypertrophy and Fibrosis through Blocking TAK1-Dependent Signaling

    PubMed Central

    Huang, He; Tang, Qi-Zhu; Wang, Ai-Bing; Chen, Manyin; Zhou, Heng; Liu, Chen; Jiang, Hong; Yang, Qinglin; Bian, Zhou-Yan; Bai, Xue; Zhu, Li-Hua; Wang, Lang; Li, Hongliang

    2010-01-01

    A20 or tumor necrosis factor–induced protein 3 is a negative regulator of nuclear factor κB signaling. A20 has been shown previously to attenuate cardiac hypertrophy in vitro and postmyocardial infarction remodeling in vivo. In the present study, we tested the hypothesis that overexpression of A20 in the murine heart would protect against cardiac hypertrophy in vivo. The effects of constitutive human A20 expression on cardiac hypertrophy were investigated using in vitro and in vivo models. Cardiac hypertrophy was produced by aortic banding in A20 transgenic mice and control animals. The extent of cardiac hypertrophy was quantitated by echocardiography, as well as by pathological and molecular analyses of heart samples. Constitutive overexpression of human A20 in the murine heart attenuated the hypertrophicresponse and markedly reduced inflammation, apoptosis, and fibrosis. Cardiac function was also preserved in hearts with increased A20 levels in response to hypertrophic stimuli. Western blot experiments further showed A20 expression markedly blocked transforming growth factor-β–activated kinase 1–dependent c-Jun N-terminal kinase/p38 signaling cascade but with no difference in either extracellular signal-regulated kinase 1/2 or AKT activation in vivo and in vitro. In cultured neonatal rat cardiac myocytes, [3H]proline incorporation and Western blot assays revealed that A20 expression suppressed transforming growth factor-β–induced collagen synthesis and transforming growth factor-β–activated kinase 1–dependent Smad 2/3/4 activation. In conclusion, A20 improves cardiac functions and inhibits cardiac hypertrophy, inflammation, apoptosis, and fibrosis by blocking transforming growth factor-β–activated kinase 1–dependent signaling. PMID:20585109

  6. Administratium: A 20th-Anniversary Update

    NASA Astrophysics Data System (ADS)

    DeBuvitz, William

    2009-01-01

    Perhaps the readers of The Physics Teacher have come across a humorous little story on the Internet about the discovery of an element called "Administratium" (or one of its variants "Governmentium," "Bureaucratium," etc.), which behaved like college administrations. Some of these readers might recall seeing it in print many years ago. In fact, it first appeared 20 years ago in the January 1989 issue of The Physics Teacher under the heading "Farcical Physics" and I was the author. I came up with the idea in February of 1988 while giving a physics exam at Middlesex County College in Edison, NJ. I was reading a memo from the college administration about the latest reorganization, with its usual increase in vice presidents, assistants to the vice presidents, etc., looked over at a large periodic chart on the wall, and it all came together. I originally posted the "Administratium" story on a bulletin board at the college and the faculty found it funny. I then decided to send it to The Physics Teacher. I was concerned about offending Middlesex College, so I asked that my name be omitted from the article. It turned out that this was unnecessary—the college administration was a good sport about it. What was surprising to me was how this little story spread. What was even more surprising was how many people took credit for it. I guess I invited this by not using my name in the original publication. If you Google "Administratium," you will get over 10,000 hits in different languages, with many people taking credit. I heard it read on The Osgood File and the discovery of "Administratium" was awarded an Ignoble Prize. A humorous story like this seems more appropriate for the Journal of Irreproducible Results. In fact, it was published in the January-February 1990 issue. Needless to say, I was getting a bit irritated by seeing so many people taking credit for my story. I contacted Norman Sperling, the editor of the JIR, about this and he suggested I write about the whole

  7. Effects of periodic discharges

    NASA Technical Reports Server (NTRS)

    Ford, F. E.

    1977-01-01

    Periodic capacity checks are assessed as well as the effects of periodic discharges on the cycle life and the performance of cells during the cycle life. Topics discussed include the effect of the amount of electrolyte on cell capacity at 35 C; battery design for spacecraft; electrolyte starvation theory; battery separator degradation; negative electrode stability; voltage regulation; operating temperatures; and integration of reconditioning systems using microprocessors.

  8. Enhancement of GluN2B Subunit-Containing NMDA Receptor Underlies Serotonergic Regulation of Long-Term Potentiation after Critical Period in the Rat Visual Cortex

    PubMed Central

    Joo, Kayoung; Rhie, Duck-Joo

    2015-01-01

    Serotonin [5-hydroxytryptamine (5-HT)] regulates synaptic plasticity in the visual cortex. Although the effects of 5-HT on plasticity showed huge diversity depending on the ages of animals and species, it has been unclear how 5-HT can show such diverse effects. In the rat visual cortex, 5-HT suppressed long-term potentiation (LTP) at 5 weeks but enhanced LTP at 8 weeks. We speculated that this difference may originate from differential regulation of neurotransmission by 5-HT between the age groups. Thus, we investigated the effects of 5-HT on apha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-, γ-aminobutyric acid receptor type A (GABAAR)-, and N-methyl-D-aspartic acid receptor (NMDAR)-mediated neurotransmissions and their involvement in the differential regulation of plasticity between 5 and 8 weeks. AMPAR-mediated currents were not affected by 5-HT at both 5 and 8 weeks. GABAAR-mediated currents were enhanced by 5-HT at both age groups. However, 5-HT enhanced NMDAR-mediated currents only at 8 weeks. The enhancement of NMDAR-mediated currents appeared to be mediated by the enhanced function of GluN2B subunit-containing NMDAR. The enhanced GABAAR- and NMDAR-mediated neurotransmissions were responsible for the suppression of LTP at 5 weeks and the facilitation of LTP at 8 weeks, respectively. These results indicate that the effects of 5-HT on neurotransmission change with development, and the changes may underlie the differential regulation of synaptic plasticity between different age groups. Thus, the developmental changes in 5-HT function should be carefully considered while investigating the 5-HT-mediated metaplastic control of the cortical network. PMID:26557019

  9. Period Pain

    MedlinePlus

    ... You may also have other symptoms, such as lower back pain, nausea, diarrhea, and headaches. Period pain is not ... Taking a hot bath Doing relaxation techniques, including yoga and meditation You might also try taking over- ...

  10. A20 Curtails Primary but Augments Secondary CD8+ T Cell Responses in Intracellular Bacterial Infection

    PubMed Central

    Just, Sissy; Nishanth, Gopala; Buchbinder, Jörn H.; Wang, Xu; Naumann, Michael; Lavrik, Inna; Schlüter, Dirk

    2016-01-01

    The ubiquitin-modifying enzyme A20, an important negative feedback regulator of NF-κB, impairs the expansion of tumor-specific CD8+ T cells but augments the proliferation of autoimmune CD4+ T cells. To study the T cell-specific function of A20 in bacterial infection, we infected T cell-specific A20 knockout (CD4-Cre A20fl/fl) and control mice with Listeria monocytogenes. A20-deficient pathogen-specific CD8+ T cells expanded stronger resulting in improved pathogen control at day 7 p.i. Imaging flow cytometry revealed that A20-deficient Listeria-specific CD8+ T cells underwent increased apoptosis and necroptosis resulting in reduced numbers of memory CD8+ T cells. In contrast, the primary CD4+ T cell response was A20-independent. Upon secondary infection, the increase and function of pathogen-specific CD8+ T cells, as well as pathogen control were significantly impaired in CD4-Cre A20fl/fl mice. In vitro, apoptosis and necroptosis of Listeria-specific A20-deficient CD8+ T cells were strongly induced as demonstrated by increased caspase-3/7 activity, RIPK1/RIPK3 complex formation and more morphologically apoptotic and necroptotic CD8+ T cells. In vitro, A20 limited CD95L and TNF-induced caspase3/7 activation. In conclusion, T cell-specific A20 limited the expansion but reduced apoptosis and necroptosis of Listeria-specific CD8+ T cells, resulting in an impaired pathogen control in primary but improved clearance in secondary infection. PMID:28004776

  11. Periodized wavelets

    SciTech Connect

    Schlossnagle, G.; Restrepo, J.M.; Leaf, G.K.

    1993-12-01

    The properties of periodized Daubechies wavelets on [0,1] are detailed and contrasted against their counterparts which form a basis for L{sup 2}(R). Numerical examples illustrate the analytical estimates for convergence and demonstrate by comparison with Fourier spectral methods the superiority of wavelet projection methods for approximations. The analytical solution to inner products of periodized wavelets and their derivatives, which are known as connection coefficients, is presented, and several tabulated values are included.

  12. [The interrelationships of the hypothalamo-neurohypophyseal, renin-angiotensin-aldosterone and prostanoid systems i regulating central hemodynamics in the acute period of traumatic disease].

    PubMed

    Barinov, E F; Ziablitsev, S V

    1995-01-01

    Experiments on white male rats with a traumatic shock by the Cannon method have permitted establishing that expressed activation of hypothalamo-neurohypophysial, renin-angiotensin-aldosterone and prostanoid systems induced disorders in the cardiovascular system, namely, a decrease in the heart stroke, growth of the vascular tension in the first hours of the acute period of the disease and an increase in the peripheral vascular resistance. Besides, the renin plasma activity falls, which may be a sanogenesis mechanism preventing redundant stimulation of the vessels and myocardium.

  13. Mycobacterium fortuitum induces A20 expression that impairs macrophage inflammatory responses.

    PubMed

    Lee, Gippeum Joy; Lee, Hye-Mi; Kim, Tae Sung; Kim, Jin Kyung; Sohn, Kyung Mok; Jo, Eun-Kyeong

    2016-04-01

    Mycobacterium fortuitum is a rapidly growing mycobacterium that has been regarded as an etiological agent of a variety of human infections. However, little is known about the host inflammatory responses and the molecular mechanisms by which MF-induced inflammation is regulated in macrophages. In this study, we report that MF infection leads to the induction of an anti-inflammatory molecule, A20 (also known as TNFAIP3), which is essential for the regulation of MF-induced inflammatory responses in murine bone marrow-derived macrophages (BMDMs). MF triggered the expression of tumor necrosis factor-α and interleukin-6 in BMDMs through signaling of the Toll-like receptor 2 (TLR2)-myeloid differentiation primary response gene 88. Additionally, MF rapidly induced the expression of A20, which inhibited proinflammatory cytokine expression and nuclear factor (NF)-κB reporter gene activities in BMDMs. Notably, MF-induced activation of NF-κB signaling was required for A20 expression and proinflammatory responses in BMDMs. Furthermore, the rough morphotype of the MF clinical strain induced a higher level of proinflammatory signaling activation, but less A20 induction in BMDMs, compared to the smooth morphotype. Taken together, these results suggest that MF-induced activation of host proinflammatory responses is negatively regulated through TLR2-dependent A20 expression.

  14. n-3 LC-PUFA deposition efficiency and appetite-regulating hormones are modulated by the dietary lipid source during rainbow trout grow-out and finishing periods.

    PubMed

    Francis, D S; Thanuthong, T; Senadheera, S P S D; Paolucci, M; Coccia, E; De Silva, S S; Turchini, G M

    2014-04-01

    Largely attributable to concerns surrounding sustainability, the utilisation of omega-3 long-chain polyunsaturated fatty acid-rich (n-3 LC-PUFA) fish oils in aquafeeds for farmed fish species is an increasingly concerning issue. Therefore, strategies to maximise the deposition efficiency of these key health beneficial fatty acids are being investigated. The present study examined the effects of four vegetable-based dietary lipid sources (linseed, olive, palm and sunflower oil) on the deposition efficiency of n-3 LC-PUFA and the circulating blood plasma concentrations of the appetite-regulating hormones, leptin and ghrelin, during the grow-out and finishing phases in rainbow trout culture. Minimal detrimental effects were noted in fish performance; however, major modifications were apparent in tissue fatty acid compositions, which generally reflected that of the diet. These modifications diminished somewhat following the fish oil finishing phase, but longer-lasting effects remained evident. The fatty acid composition of the alternative oils was demonstrated to have a modulatory effect on the deposition efficiency of n-3 LC-PUFA and on the key endocrine hormones involved in appetite regulation, growth and feed intake during both the grow-out and finishing phases. In particular, n-6 PUFA (sunflower oil diet) appeared to 'spare' the catabolism of n-3 LC-PUFA and, as such, resulted in the highest retention of these fatty acids, ultimately highlighting new nutritional approaches to maximise the maintenance of the qualitative benefits of fish oils when they are used in feeds for aquaculture species.

  15. Differential expression and regulation of cylooxygenases, prostaglandin E synthases and prostacyclin synthase in rat uterus during the peri-implantation period.

    PubMed

    Cong, Jing; Diao, Hong-Lu; Zhao, Yue-Chao; Ni, Hua; Yan, Yun-Qin; Yang, Zeng-Ming

    2006-01-01

    It has been shown that both prostaglandin I2 (PGI2) and PGE2 are essential for mouse implantation, whereas only PGE2 is required for hamster implantation. To date, the expression and regulation of cyclooxygenase (COX) and prostaglandin E synthase (PGES), which are responsible for PGE2 production, have not been reported in the rat. The aim of this study was to examine the expression pattern and regulation of COX-1, COX-2, membrane-associated PGES-1 (mPGES-1), mPGES-2 and cytosolic PGES (cPGES) in rat uterus during early pregnancy and pseudopregnancy, and under delayed implantation. At implantation site on day 6 of pregnancy, COX-1 immunostaining was highly visible in the luminal epithelium, and COX-2 immunostaining was clearly observed in the subluminal stroma. Both mPGES-1 mRNA and protein were only observed in the subluminal stroma surrounding the implanting blastocyst at the implantation site on day 6 of pregancy , but were not seen in the inter-implantation site on day 6 of pregnancy and on day 6 of pseudopregnancy. Our data suggest that the presence of an active blastocyst is required for mPGES-1 expression at the implantation site. When pregnant rats on day 5 were treated with nimesulide for 24 h, mPGES-1 protein expression was completely inhibited. cPGES immunostaining was clearly observed in the luminal epithelium and subluminal stromal cells immediately surrounding the implanting blastocyst on day 6 of pregnancy. mPGES-2 immunostaining was clearly seen in the luminal epithelium at the implantation site. Additionally, immunostaining for prostaglandin I synthase (PGIS) was also strongly detected at the implantation site. In conclusion, our results indicate that PGE2 and PGI2 should have a very important role in rat implantation.

  16. Medicare and Medicaid programs: Hospital Outpatient Prospective Payment and Ambulatory Surgical Center Payment Systems and Quality Reporting Programs; electronic reporting pilot; Inpatient Rehabilitation Facilities Quality Reporting Program; revision to Quality Improvement Organization regulations. Final rule with comment period.

    PubMed

    2012-11-15

    This final rule with comment period revises the Medicare hospital outpatient prospective payment system (OPPS) and the Medicare ambulatory surgical center (ASC) payment system for CY 2013 to implement applicable statutory requirements and changes arising from our continuing experience with these systems. In this final rule with comment period, we describe the changes to the amounts and factors used to determine the payment rates for Medicare services paid under the OPPS and those paid under the ASC payment system. In addition, this final rule with comment period updates and refines the requirements for the Hospital Outpatient Quality Reporting (OQR) Program, the ASC Quality Reporting (ASCQR) Program, and the Inpatient Rehabilitation Facility (IRF) Quality Reporting Program. We are continuing the electronic reporting pilot for the Electronic Health Record (EHR) Incentive Program, and revising the various regulations governing Quality Improvement Organizations (QIOs), including the secure transmittal of electronic medical information, beneficiary complaint resolution and notification processes, and technical changes. The technical changes to the QIO regulations reflect CMS' commitment to the general principles of the President's Executive Order on Regulatory Reform, Executive Order 13563 (January 18, 2011).

  17. Molecular Basis for the Unique Deubiquitinating Activity of the NF-κB Inhibitor A20

    SciTech Connect

    Lin, S.; Chung, J; Lamothe, B; Rajashankar, K; Lu, M; Lo, Y; Lam, A; Darnay, B; Wu, H

    2008-01-01

    Nuclear factor ?B (NF-?B) activation in tumor necrosis factor, interleukin-1, and Toll-like receptor pathways requires Lys63-linked nondegradative polyubiquitination. A20 is a specific feedback inhibitor of NF-?B activation in these pathways that possesses dual ubiquitin-editing functions. While the N-terminal domain of A20 is a deubiquitinating enzyme (DUB) for Lys63-linked polyubiquitinated signaling mediators such as TRAF6 and RIP, its C-terminal domain is a ubiquitin ligase (E3) for Lys48-linked degradative polyubiquitination of the same substrates. To elucidate the molecular basis for the DUB activity of A20, we determined its crystal structure and performed a series of biochemical and cell biological studies. The structure reveals the potential catalytic mechanism of A20, which may be significantly different from papain-like cysteine proteases. Ubiquitin can be docked onto a conserved A20 surface; this interaction exhibits charge complementarity and no steric clash. Surprisingly, A20 does not have specificity for Lys63-linked polyubiquitin chains. Instead, it effectively removes Lys63-linked polyubiquitin chains from TRAF6 without dissembling the chains themselves. Our studies suggest that A20 does not act as a general DUB but has the specificity for particular polyubiquitinated substrates to assure its fidelity in regulating NF-?B activation in the tumor necrosis factor, interleukin-1, and Toll-like receptor pathways.

  18. Live imaging-based model selection reveals periodic regulation of the stochastic G1/S phase transition in vertebrate axial development.

    PubMed

    Sugiyama, Mayu; Saitou, Takashi; Kurokawa, Hiroshi; Sakaue-Sawano, Asako; Imamura, Takeshi; Miyawaki, Atsushi; Iimura, Tadahiro

    2014-12-01

    In multicellular organism development, a stochastic cellular response is observed, even when a population of cells is exposed to the same environmental conditions. Retrieving the spatiotemporal regulatory mode hidden in the heterogeneous cellular behavior is a challenging task. The G1/S transition observed in cell cycle progression is a highly stochastic process. By taking advantage of a fluorescence cell cycle indicator, Fucci technology, we aimed to unveil a hidden regulatory mode of cell cycle progression in developing zebrafish. Fluorescence live imaging of Cecyil, a zebrafish line genetically expressing Fucci, demonstrated that newly formed notochordal cells from the posterior tip of the embryonic mesoderm exhibited the red (G1) fluorescence signal in the developing notochord. Prior to their initial vacuolation, these cells showed a fluorescence color switch from red to green, indicating G1/S transitions. This G1/S transition did not occur in a synchronous manner, but rather exhibited a stochastic process, since a mixed population of red and green cells was always inserted between newly formed red (G1) notochordal cells and vacuolating green cells. We termed this mixed population of notochordal cells, the G1/S transition window. We first performed quantitative analyses of live imaging data and a numerical estimation of the probability of the G1/S transition, which demonstrated the existence of a posteriorly traveling regulatory wave of the G1/S transition window. To obtain a better understanding of this regulatory mode, we constructed a mathematical model and performed a model selection by comparing the results obtained from the models with those from the experimental data. Our analyses demonstrated that the stochastic G1/S transition window in the notochord travels posteriorly in a periodic fashion, with doubled the periodicity of the neighboring paraxial mesoderm segmentation. This approach may have implications for the characterization of the

  19. Disruption of CLOCK-BMAL1 Transcriptional Activity Is Responsible for Aryl Hydrocarbon Receptor–Mediated Regulation of Period1 Gene

    PubMed Central

    Xu, Can-Xin; Krager, Stacey L.; Liao, Duan-Fang; Tischkau, Shelley A.

    2010-01-01

    The aryl hydrocarbon receptor (AhR) is a period-aryl hydrocarbon receptor nuclear transporter-simple minded domain transcription factor that shares structural similarity with circadian clock genes and readily interacts with components of the molecular clock. Activation of AhR by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters behavioral circadian rhythms and represses the Period1 (Per1) gene in murine hematopoietic stem and progenitor cells. Per1 expression is driven by circadian locomotor activity cycles kaput-brain muscle ARNT-like (CLOCK-BMAL1)–dependent activation of Eboxes in the Per1 promoter. We hypothesized that the effects of AhR activation on the circadian clock are mediated by disruption of CLOCK-BMAL1 function and subsequent Per1 gene suppression. Effects of AhR activation on rhythmic Per1 transcripts were examined in livers of mice after treatment with the AhR agonist, TCDD; the molecular mechanisms of Per1 repression by AhR were determined in hepatoma cells using TCDD and β-napthoflavone as AhR activators. This study reports, for the first time, that AhR activation by TCDD alters the Per1 rhythm in the mouse liver and that Per1 gene suppression depends upon the presence of AhR. Furthermore, AhR interaction with BMAL1 attenuates CLOCK-BMAL1 activity and decreases CLOCK binding at Ebox1 and Ebox3 in the Per1 promoter. Taken together, these data suggest that AhR activation represses Per1 through disrupting CLOCK-BMAL1 activity, producing dysregulation of rhythmic Per1 gene expression. These data define alteration of the Per1 rhythm as novel signaling events downstream of AhR activation. Downregulation of Per1 could contribute to metabolic disease, cancer, and other detrimental effects resulting from exposure to certain environmental pollutants. PMID:20106950

  20. Live Imaging-Based Model Selection Reveals Periodic Regulation of the Stochastic G1/S Phase Transition in Vertebrate Axial Development

    PubMed Central

    Kurokawa, Hiroshi; Sakaue-Sawano, Asako; Imamura, Takeshi; Miyawaki, Atsushi; Iimura, Tadahiro

    2014-01-01

    In multicellular organism development, a stochastic cellular response is observed, even when a population of cells is exposed to the same environmental conditions. Retrieving the spatiotemporal regulatory mode hidden in the heterogeneous cellular behavior is a challenging task. The G1/S transition observed in cell cycle progression is a highly stochastic process. By taking advantage of a fluorescence cell cycle indicator, Fucci technology, we aimed to unveil a hidden regulatory mode of cell cycle progression in developing zebrafish. Fluorescence live imaging of Cecyil, a zebrafish line genetically expressing Fucci, demonstrated that newly formed notochordal cells from the posterior tip of the embryonic mesoderm exhibited the red (G1) fluorescence signal in the developing notochord. Prior to their initial vacuolation, these cells showed a fluorescence color switch from red to green, indicating G1/S transitions. This G1/S transition did not occur in a synchronous manner, but rather exhibited a stochastic process, since a mixed population of red and green cells was always inserted between newly formed red (G1) notochordal cells and vacuolating green cells. We termed this mixed population of notochordal cells, the G1/S transition window. We first performed quantitative analyses of live imaging data and a numerical estimation of the probability of the G1/S transition, which demonstrated the existence of a posteriorly traveling regulatory wave of the G1/S transition window. To obtain a better understanding of this regulatory mode, we constructed a mathematical model and performed a model selection by comparing the results obtained from the models with those from the experimental data. Our analyses demonstrated that the stochastic G1/S transition window in the notochord travels posteriorly in a periodic fashion, with doubled the periodicity of the neighboring paraxial mesoderm segmentation. This approach may have implications for the characterization of the

  1. The transcription factor DREAM represses A20 and mediates inflammation

    PubMed Central

    Tiruppathi, Chinnaswamy; Soni, Dheeraj; Wang, Dong-Mei; Xue, Jiaping; Singh, Vandana; Thippegowda, Prabhakar B.; Cheppudira, Bopaiah P.; Mishra, Rakesh K.; DebRoy, Auditi; Qian, Zhijian; Bachmaier, Kurt; Zhao, Youyang; Christman, John W.; Vogel, Stephen M.; Ma, Averil; Malik, Asrar B.

    2014-01-01

    Here we show that the transcription-repressor DREAM binds to the A20 promoter to repress the expression of A20, the deubiquitinase suppressing inflammatory NF-κB signaling. DREAM-deficient (Dream−/−) mice displayed persistent and unchecked A20 expression in response to endotoxin. DREAM functioned by transcriptionally repressing A20 through binding to downstream regulatory elements (DREs). In contrast, USF1 binding to the DRE-associated E-box domain activated A20 expression in response to inflammatory stimuli. These studies define the critical opposing functions of DREAM and USF1 in inhibiting and inducing A20 expression, respectively, and thereby the strength of NF-κB signaling. Targeting of DREAM to induce USF1-mediated A20 expression is therefore a potential anti-inflammatory strategy in diseases such as acute lung injury associated with unconstrained NF-κB activity. PMID:24487321

  2. A20 modulates lipid metabolism and energy production to promote liver regeneration.

    PubMed

    Damrauer, Scott M; Studer, Peter; da Silva, Cleide G; Longo, Christopher R; Ramsey, Haley E; Csizmadia, Eva; Shrikhande, Gautam V; Scali, Salvatore T; Libermann, Towia A; Bhasin, Manoj K; Ferran, Christiane

    2011-03-17

    Liver regeneration is clinically of major importance in the setting of liver injury, resection or transplantation. We have demonstrated that the NF-κB inhibitory protein A20 significantly improves recovery of liver function and mass following extended liver resection (LR) in mice. In this study, we explored the Systems Biology modulated by A20 following extended LR in mice. We performed transcriptional profiling using Affymetrix-Mouse 430.2 arrays on liver mRNA retrieved from recombinant adenovirus A20 (rAd.A20) and rAd.βgalactosidase treated livers, before and 24 hours after 78% LR. A20 overexpression impacted 1595 genes that were enriched for biological processes related to inflammatory and immune responses, cellular proliferation, energy production, oxidoreductase activity, and lipid and fatty acid metabolism. These pathways were modulated by A20 in a manner that favored decreased inflammation, heightened proliferation, and optimized metabolic control and energy production. Promoter analysis identified several transcriptional factors that implemented the effects of A20, including NF-κB, CEBPA, OCT-1, OCT-4 and EGR1. Interactive scale-free network analysis captured the key genes that delivered the specific functions of A20. Most of these genes were affected at basal level and after resection. We validated a number of A20's target genes by real-time PCR, including p21, the mitochondrial solute carriers SLC25a10 and SLC25a13, and the fatty acid metabolism regulator, peroxisome proliferator activated receptor alpha. This resulted in greater energy production in A20-expressing livers following LR, as demonstrated by increased enzymatic activity of cytochrome c oxidase, or mitochondrial complex IV. This Systems Biology-based analysis unravels novel mechanisms supporting the pro-regenerative function of A20 in the liver, by optimizing energy production through improved lipid/fatty acid metabolism, and down-regulated inflammation. These findings support pursuit of A

  3. Progesterone regulation of Na/K-ATPase β1 subunit expression in the mouse uterus during the peri-implantation period.

    PubMed

    Deng, Wen-Bo; Tian, Zhen; Liang, Xiao-Huan; Wang, Bao-Chen; Yang, Feng; Yang, Zeng-Ming

    2013-05-01

    Luminal closure and embryo apposition are essential for blastocyst attachment during early pregnancy. In our preliminary microarray results (unpublished data), sodium-potassium adenosine triphosphatase (Na/K-ATPase) β1 (Atp1b1) was highly expressed in mouse uterus on Days 3 and 4 of pregnancy. However, expression and regulation of Atp1b1 in the mammalian uterus during early pregnancy are unknown. Using in situ hybridization, a strong level of Atp1b1 mRNA was detected in luminal epithelial cells on Days 3 and 4 of pregnancy (Day 1 = day of vaginal plug). The expression pattern of FXYD domain-containing ion transport regulator 4 (Fxyd4) was similar to that of Atp1b1. Real-time reverse transcription polymerase chain reaction confirmed the high expression level of Atp1b1 mRNA. Compared with Day 1, the mRNA level of Atp1b1 on Days 3 and 4 increased by 3.5 ± 0.5 and 4.5 ± 0.5 fold, respectively. When the embryo invaded through epithelial cells into the maternal stromal compartment on day 5, Atp1b1 expression decreased to a basal level. Progesterone stimulated Atp1b1 expression by 2.8 ± 1 fold compared with oil in ovariectomized mice at 24 hours after treatment. Expression of Atp1b1 was further upregulated to 4 ± 0.4 fold by estrogen and progesterone. Based on time-course study, progesterone rapidly induced Atp1b1 expression at 6 and 12 hours (13.7 ± 0.5 and 16.6 ± 1.4, respectively); furthermore, this upregulation was blocked by RU486 (progesterone receptor antagonist). Transcription activity of the Atp1b1 promoter was (Day 1 = day of vaginal plug) stimulated by CCAAT/enhancer binding protein beta (Cebpb). In conclusion, Atp1b1 was highly expressed in luminal epithelium during peri-implantation and upregulated by progesterone.

  4. Nandrolone-pretreatment enhances cardiac beta(2)-adrenoceptor expression and reverses heart contractile down-regulation in the post-stress period of acute-stressed rats.

    PubMed

    Penna, Claudia; Abbadessa, Giuliana; Mancardi, Daniele; Spaccamiglio, Angela; Racca, Silvia; Pagliaro, Pasquale

    2007-10-01

    To investigate whether nandrolone decanoate (ND)-pretreatment can modulate (1) beta-adrenoceptor expression and (2) myocardial contractility in response to beta-adrenoceptors stimulation with isoproterenol (ISO), in hearts of both normal and stressed rats. Rats were treated with 15 mg/(kgday) of Deca-Durabolin (ND, 1 ml i.m.) or with vehicle (oil) for 14 days. The day after the last injection, the dose-response to ISO (1 x 10(-8), 5 x 10(-8) and 10(-7)M), was studied in isolated rat hearts harvested from unstressed animals (unstressed+vehicle (control) or unstressed+ND) or from stressed animals (stressed+vehicle or stressed+ND): acute stress protocol consisted in restrain for 1h immediately before sacrifice. ND-pretreatment increased beta(2)-adrenoceptor expression. In baseline conditions all hearts had a similar left ventricular developed pressure (LVDP) and maximum rate of increase of LVDP (dP/dt(max)). In hearts of unstressed+vehicle or unstressed+ND, ISO caused a similar increase in LVDP (+90-100%) and dP/dt(max) (+120-150%). However, hearts of stressed+vehicle animals showed a marked depression of inotropic response to ISO (i.e. for ISO 1 x 10(-8),-55% in LVDP response versus unstressed). Yet, in hearts of stressed+ND-animals the effect of stress was reversed, showing the highest response to ISO (i.e. for ISO 1 x 10(-7), +30% LVDP response versus unstressed). The ND-induced beta(2)-adrenoceptor overexpression does not affect ISO-response in unstressed animals. However, acute stress induces a down-regulation of ISO-response, which is reversed by ND-pretreatment. Since the physiological post-stress down-regulation of adrenergic-response is absent after nandrolone treatment, the heart may be exposed to a sympathetic over-stimulation. This might represent a risk for cardiovascular incidents in anabolic steroid addicts under stressing conditions.

  5. 7 CFR 966.16 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 966.16 Section 966.16 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulating Handling Definitions § 966.16 Fiscal period. Fiscal period means the period beginning August 1 and...

  6. 7 CFR 959.16 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 959.16 Section 959.16 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulating Handling Definitions § 959.16 Fiscal period. Fiscal period means the annual period beginning...

  7. 7 CFR 948.10 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 948.10 Section 948.10 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Order Regulating Handling Definitions § 948.10 Fiscal period. Fiscal period means the period...

  8. 7 CFR 946.9 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 946.9 Section 946.9 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Order Regulating Handling Definitions § 946.9 Fiscal period. Fiscal period means the period beginning...

  9. The effect of metformin on neuronal activity in the appetite-regulating brain regions of mice fed a high-fat diet during an anorectic period.

    PubMed

    Kim, Hyun-Ju; Jin, Bo-Yeong; Oh, Mi-Jeong; Shin, Kyung-Ho; Choi, Sang-Hyun; Kim, Dong-Hoon

    2016-02-01

    Metformin reduces body weight by decreasing food intake in humans and animals. However, the brain regions involved in metformin-induced anorexia remain unclear. Therefore, we investigated c-Fos expression (FOS), a marker of neuronal activity, in the appetite-regulating brain regions after oral administration of metformin (PO, 300mg/kg daily for 1 or 3days) or vehicle. The body weight and food intake decreased in mice treated with metformin for 3days (RM group) and mice that had the same amount of food as the RM group (Pair-fed group; PF) compared to the control group. FOS expression levels increased in the paraventricular nucleus, area postrema, and central amygdala of mice administered an acute single dose of metformin (SM group) compared to the control mice. In the nucleus tractus solitarius, the FOS expression levels increased in both the SM and RM groups compared to the control group. The FOS expression levels also increased in the nucleus accumbens of the RM group compared to other groups. The FOS expression levels decreased in the ventromedial hypothalamic nucleus in the PF group, but not the RM group, compared to the control group, suggesting a potential hypothalamic area involvement for metformin-induced anorexia. These results suggest that both the hypothalamic and extra-hypothalamic regions are associated with metformin-induced anorexia, which is dependent on metformin treatment duration.

  10. Elaborate regulations of the predator-induced polyphenism in the water flea Daphnia pulex: kairomone-sensitive periods and life-history tradeoffs.

    PubMed

    Imai, Maki; Naraki, Yuka; Tochinai, Shin; Miura, Toru

    2009-12-01

    Adaptive polyphenism produces alternative phenotypes depending on environmental stimuli. The water flea Daphnia pulex shows predator-induced polyphenism, facultatively forming neckteeth in response to kairomones released by Chaoborus larvae. This study was designed to reveal the regulatory systems producing the defensive morph during embryonic and postembryonic development. As noted previously, the crest epithelium at the site of neckteeth is shown to thicken earlier the neckteeth formation, and the neckteeth number increased until the third instar, and later disappeared. Exposure to kairomone at various time points and intervals during development showed that the signal was required even at early postembryonic stages to maintain neckteeth. Moreover, two different induction methods, i.e. embryonic and maternal exposures, enabled us to discriminate maternal and zygotic effects in response to kairomone. Direct embryonic exposure is shown to be sufficient to form neckteeth without maternal effect although their growth was diminished; namely, there is a trade-off for neckteeth production. However, maternal exposures resulted in larger progenies in smaller numbers, suggesting that the mother daphnids change their reproductive strategy depending on kairomone signals. Taken together, the developmental responses to the presence of predators are regulated elaborately at various levels.

  11. Periodic Polymers

    NASA Astrophysics Data System (ADS)

    Thomas, Edwin

    2013-03-01

    Periodic polymers can be made by self assembly, directed self assembly and by photolithography. Such materials provide a versatile platform for 1, 2 and 3D periodic nano-micro scale composites with either dielectric or impedance contrast or both, and these can serve for example, as photonic and or phononic crystals for electromagnetic and elastic waves as well as mechanical frames/trusses. Compared to electromagnetic waves, elastic waves are both less complex (longitudinal modes in fluids) and more complex (longitudinal, transverse in-plane and transverse out-of-plane modes in solids). Engineering of the dispersion relation between wave frequency w and wave vector, k enables the opening of band gaps in the density of modes and detailed shaping of w(k). Band gaps can be opened by Bragg scattering, anti-crossing of bands and discrete shape resonances. Current interest is in our group focuses using design - modeling, fabrication and measurement of polymer-based periodic materials for applications as tunable optics and control of phonon flow. Several examples will be described including the design of structures for multispectral band gaps for elastic waves to alter the phonon density of states, the creation of block polymer and bicontinuous metal-carbon nanoframes for structures that are robust against ballistic projectiles and quasi-crystalline solid/fluid structures that can steer shock waves.

  12. Body condition score and plane of nutrition prepartum affect adipose tissue transcriptome regulators of metabolism and inflammation in grazing dairy cows during the transition period.

    PubMed

    Vailati-Riboni, M; Kanwal, M; Bulgari, O; Meier, S; Priest, N V; Burke, C R; Kay, J K; McDougall, S; Mitchell, M D; Walker, C G; Crookenden, M; Heiser, A; Roche, J R; Loor, J J

    2016-01-01

    Recent studies demonstrating a higher incidence of metabolic disorders after calving have challenged the management practice of increasing dietary energy density during the last ~3 wk prepartum. Despite our knowledge at the whole-animal level, the tissue-level mechanisms that are altered in response to feeding management prepartum remain unclear. Our hypothesis was that prepartum body condition score (BCS), in combination with feeding management, plays a central role in the peripartum changes associated with energy balance and inflammatory state. Twenty-eight mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to 1 of 4 treatment groups in a 2 × 2 factorial arrangement: 2 prepartum BCS categories (4.0 and 5.0, based on a 10-point scale; BCS4, BCS5) obtained via differential feeding management during late-lactation, and 2 levels of energy intake during the 3 wk preceding calving (75 and 125% of estimated requirements). Subcutaneous adipose tissue was harvested via biopsy at -1, 1, and 4 wk relative to parturition. Quantitative polymerase chain reaction was used to measure mRNA and microRNA (miRNA) expression of targets related to fatty acid metabolism (lipogenesis, lipolysis), adipokine synthesis, and inflammation. Both prepartum BCS and feeding management had a significant effect on mRNA and miRNA expression throughout the peripartum period. Overfed BCS5 cows had the greatest prepartum expression of fatty acid synthase (FASN) and an overall greater expression of leptin (LEP); BCS5 was also associated with greater overall adiponectin (ADIPOQ) and peroxisome proliferator-activated receptor gamma (PPARG), whereas overfeeding upregulated expression of proadipogenic miRNA. Higher postpartum expression of chemokine ligand 5 (CCL5) and the cytokines interleukin 6 (IL6) and tumor necrosis factor (TNF) was detected in overfed BCS5 cows. Feed-restricted BCS4 cows had the highest overall interleukin 1 (IL1B) expression. Prepartum feed restriction

  13. Transcription regulation of gene expression in rat brown adipose tissue in response to unloading or 2G loading during growing period

    NASA Astrophysics Data System (ADS)

    Watanabe, S.; Hitomi, Y.; Kawano, F.; Ohira, Y.; Kizaki, T.; Nakano, N.; Sakurai, T.; Izawa, T.; Suzuki, K.; Sudoh, M.; Roy, R. R.; Ohno, H.

    2007-05-01

    The effects were investigated of long-term unloading and macrogravity on the expression of 15 genes at the mRNA levels in brown adipose tissue (BAT) from rat pups, particularly focusing on uncoupling protein (UCP) family, nitric oxide synthase (NOS) isoenzymes, and antioxidant enzymes. The animals in the unloaded group (a simulation model of spaceflight) were hindlimb-unloaded by tail suspension between postnatal day 4 and month 3, followed by 2-mo ambulation recovery. Moreover, centrifugation at 2G (an imitation of the hypergravity effects) was performed during the same period as the unloading, also followed by 2-mo ambulation recovery (adaptation to 1G from 2G). Compared with the age-matched control group, significantly lower expression levels of mRNA for UCP2, iNOS, and Cu,Zn-superoxide dismutase (Cu, Zn-SOD) in BAT were observed immediately after unloading, but not immediately after exposure to 2G. During 2-mo ambulation recovery from both extreme conditions, the expression of mRNA for Mn-SOD was enhanced, suggesting an increase in oxidative stress. These findings suggest that both micro- and macrogravity may have some influence upon the function of BAT, and that changes in the BAT function may be involved in the mechanisms subserving adaptation to such extreme conditions by what humans have to be faced with during the spaceflight and return to 1G.

  14. MicroRNA regulation in extreme environments: differential expression of microRNAs in the intertidal snail Littorina littorea during extended periods of freezing and anoxia.

    PubMed

    Biggar, Kyle K; Kornfeld, Samantha F; Maistrovski, Yulia; Storey, Kenneth B

    2012-10-01

    Several recent studies of vertebrate adaptation to environmental stress have suggested roles for microRNAs (miRNAs) in regulating global suppression of protein synthesis and/or restructuring protein expression patterns. The present study is the first to characterize stress-responsive alterations in the expression of miRNAs during natural freezing or anoxia exposures in an invertebrate species, the intertidal gastropod Littorina littorea. These snails are exposed to anoxia and freezing conditions as their environment constantly fluctuates on both a tidal and seasonal basis. The expression of selected miRNAs that are known to influence the cell cycle, cellular signaling pathways, carbohydrate metabolism and apoptosis was evaluated using RT-PCR. Compared to controls, significant changes in expression were observed for miR-1a-1, miR-34a and miR-29b in hepatopancreas and for miR-1a-1, miR-34a, miR-133a, miR-125b, miR-29b and miR-2a in foot muscle after freezing exposure at -6 °C for 24 h (P<0.05). In addition, in response to anoxia stress for 24 h, significant changes in expression were also observed for miR-1a-1, miR-210 and miR-29b in hepatopancreas and for miR-1a-1, miR-34a, miR-133a, miR-29b and miR-2a in foot muscle (P<0.05). Moreover, protein expression of Dicer, an enzyme responsible for mature microRNA processing, was increased in foot muscle during freezing and anoxia and in hepatopancreas during freezing. Alterations in expression of these miRNAs in L. littorea tissues may contribute to organismal survival under freezing and anoxia.

  15. Long-Term Instructional Development: A 20-Year ID and Implementation Project.

    ERIC Educational Resources Information Center

    Sullivan, Howard; Ice, Kay; Niedermeyer, Fred

    2000-01-01

    Discussion of long-term instructional development focuses on the development and implementation of a K-12 energy education curriculum over a 20-year period. Highlights include field testing; fund raising; learner performance on posttests; revisions and updates; and guidelines for long-term instructional development projects. (LRW)

  16. A20--an omnipotent protein in the liver: prometheus myth resolved?

    PubMed

    da Silva, Cleide Gonçalves; Cervantes, Jesus Revuelta; Studer, Peter; Ferran, Christiane

    2014-01-01

    Contribution of NF-kappaB inhibitory and ubiquitin-editing A20 (tnfaip3) to the liver's protective response to injury, particularly to its anti-inflammatory armamentarium, is exemplified by the dramatic phenotype of A20 knockout mice that die prematurely of unfettered inflammation predominantly in the liver. A number of additional studies originating from our laboratory and others clearly demonstrate that A20 is part of the liver response to injury and resection. Upregulation of A20 in hepatocytes serves a broad hepatoprotective goal through combined anti-inflammatory, anti-apoptotic, anti-oxidant and pro-regenerative functions. The molecular basis for A20's hepatoprotective functions were partially resolved and include blockade of NF-kappaB activation in support of its anti-inflammatory function, inhibition of pro-caspase 8 cleavage in support of its anti-apoptotic function, increasing Peroxisome Proliferator Activated Receptor alpha (PPARalpha) expression in support of its anti-oxidant function, and decreasing Cyclin Dependent Kinase Inhibitor p21 while boosting IL-6/STAT3 proliferative signals as part of its pro-regenerative function. In experimental animal models, overexpression of A20 in the liver protects from radical acute fulminant toxic hepatitis, lethal hepatectomy, and severe liver ischemia reperfusion injury (IRI), and allows successful engraftment of marginal liver grafts. Conversely, partial loss of A20, as in A20 heterozygote mice, significantly impairs liver regeneration and damage, which confers high lethality to an otherwise safe procedure i.e., 2/3 partial hepatectomy. This is the ultimate proof of the physiologic role of A20 in liver regeneration and repair. In recent work, A20's functions in the liver have expanded to encompass regulation of lipid and glucose metabolism, unlocking a whole new set of metabolic diseases that could be affected by A20. In this chapter we review all available data regarding A20's physiologic role in the liver, and

  17. Relapse to cocaine-seeking increases activity-regulated gene expression differentially in the striatum and cerebral cortex of rats following short or long periods of abstinence.

    PubMed

    Hearing, M C; See, R E; McGinty, J F

    2008-09-01

    One of the most insidious features of cocaine addiction is a high rate of relapse even after extended periods of abstinence. A wide variety of drug-associated stimuli, including the context in which a drug is taken, can gain incentive motivational properties that trigger drug desire and relapse to drug-seeking. Both animal and clinical studies suggest that extensive cocaine exposure may induce a transition from cortical to striatal control over decision-making as compulsive drug-seeking emerges. Using an animal model of relapse to cocaine-seeking, the present study investigated the expression patterns of three different activity-related genes (c-fos, zif/268, and arc) in cortical and striatal brain regions implicated in compulsive drug-seeking in order to determine the neuroadaptations that occur during context-induced relapse following brief or prolonged abstinence from cocaine self-administration. Re-exposure to the environment previously associated with cocaine self-administration following 22 h or 15 days of abstinence produced a significant increase in zif/268 and arc, but not c-fos mRNA, in the caudate-putamen and nucleus accumbens. With the exception of arc mRNA levels following 15 days of abstinence, all three genes were increased in the anterior cingulate cortex of animals with a cocaine history when they were re-exposed to the operant chamber. Additionally, c-fos, zif/268, and arc expression was differentially affected in the motor and sensory cortices at both timepoints. Together, these results support convergent evidence that drug-seeking induced by a cocaine-paired context changes the activity of corticostriatal circuits.

  18. A20 controls intestinal homeostasis through cell-specific activities.

    PubMed

    Vereecke, Lars; Vieira-Silva, Sara; Billiet, Thomas; van Es, Johan H; Mc Guire, Conor; Slowicka, Karolina; Sze, Mozes; van den Born, Maaike; De Hertogh, Gert; Clevers, Hans; Raes, Jeroen; Rutgeerts, Paul; Vermeire, Severine; Beyaert, Rudi; van Loo, Geert

    2014-09-30

    The transcription factor NF-κB is indispensable for intestinal immune homeostasis, but contributes to chronic inflammation and inflammatory bowel disease (IBD). A20, an inhibitor of both NF-κB and apoptotic signalling, was identified as a susceptibility gene for multiple inflammatory diseases, including IBD. Despite absence of spontaneous intestinal inflammation in intestinal epithelial cell (IEC) specific A20 knockout mice, we found additional myeloid-specific A20 deletion to synergistically drive intestinal pathology through cell-specific mechanisms. A20 ensures intestinal barrier stability by preventing cytokine-induced IEC apoptosis, while A20 prevents excessive cytokine production in myeloid cells. Combining IEC and myeloid A20 deletion induces ileitis and severe colitis, characterized by IEC apoptosis, Paneth and goblet cell loss, epithelial hyperproliferation and intestinal microbiota dysbiosis. Continuous epithelial cell death and regeneration in an inflammatory environment sensitizes cells for neoplastic transformation and the development of colorectal tumours in aged mice.

  19. Nuclear apoJ: A low dose radiation inducible regulator of cell death. Final report for period September 15, 1998 - September 14, 2001

    SciTech Connect

    Aronow, Bruce J.

    2002-04-19

    gene targeting to increasing levels of ionizing radiation from a Cesium source. Data gathered under the support of this grant application initially indicated that apoJ deficient animals were more resistant to radiation, but as we accumulated more and more data points and covered a tighter exposure range, the genotype-based differences became insignificant. However, the possibility existed that because mortality based radiation-resistance could be attributable to mechanism for which nuclear apoJ was not rate determining, we maintained a very large of colony of apoJ knockout and wildtype animals in both the C57/B16 and Cv129 strain backgrounds that were exposed to sub-lethal levels of ionizing radiation to monitor for the occurrence of tumors. These animals were allowed to fully recover and age normally in either germ free or normal animal housing. Our results demonstrated no significant differences between wildtype and apoJ knockout animals over a period that extended up to 30 months for individual animals. We recorded similar weight gain, a relatively low mortality rate, and a similar mixture and rate of sarcoma and adenocarcinomas after surviving the initial ionizing radiation exposures. Thus we conclude that apoJ gene function, which was totally eliminated by our gene targeting, did not influence radiation sensitivity or serve as a tumor suppressor in response to DNA damage.

  20. Lack of the ubiquitin-editing enzyme A20 results in loss of hematopoietic stem cell quiescence

    PubMed Central

    Nakagawa, Masahiro Marshall; Thummar, Keyur; Mandelbaum, Jonathan; Pasqualucci, Laura

    2015-01-01

    A balance between quiescence and proliferation is critical for proper maintenance of the hematopoietic stem cell (HSC) pool. Although a lot is known about hematopoiesis, molecular mechanisms that control HSC quiescence remain largely unknown. The ubiquitin-editing enzyme A20 functions as a central regulator of inflammation and adaptive immunity. Here, we show that a deficiency of A20 in the hematopoietic system causes anemia, lymphopenia, and postnatal lethality. Lack of A20 in HSCs results in diminished pool size, impaired radioprotection, defective repopulation, and loss of quiescence. A20-deficient HSCs display increased IFN-γ signaling, caused by augmented NF-κB activation. Strikingly, deletion of both IFN-γ and A20 in hematopoietic cells results in partial rescue of the HSC phenotype. We anticipate that our experiments will facilitate the understanding of mechanisms through which A20-mediated inflammatory signals control HSC quiescence and functions. PMID:25624445

  1. 8 CFR 245a.20 - Decisions, appeals, motions, and certifications.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... aliens previously in proceedings—(1) Upon the granting of an application. If the application for LIFE... 8 Aliens and Nationality 1 2013-01-01 2013-01-01 false Decisions, appeals, motions, and certifications. 245a.20 Section 245a.20 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY...

  2. 8 CFR 245a.20 - Decisions, appeals, motions, and certifications.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... aliens previously in proceedings—(1) Upon the granting of an application. If the application for LIFE... 8 Aliens and Nationality 1 2014-01-01 2014-01-01 false Decisions, appeals, motions, and certifications. 245a.20 Section 245a.20 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY...

  3. Altered speech following adenoidectomy: a 20 year experience.

    PubMed

    Stewart, K J; Ahmad, T; Razzell, R E; Watson, A C H

    2002-09-01

    Altered speech related to velopharyngeal insufficiency is a rare but well-recognised complication of adenoidectomy. Over a 20 year period, 42 patients were referred to the Edinburgh cleft team for investigation of altered speech persisting for more than 12 months after adenoidectomy. We studied the cases to ascertain the incidence, clinical features and causes of altered speech in these patients and to assess the efficacy of a selective treatment policy. All data were prospectively collected when the patients were assessed in a multidisciplinary clinic and investigated by videofluoroscopy. Nasopharyngoscopy was also possible in half of the patients. Overall, 27 patients were male and 15 were female, and their mean age was 6.5 years. The incidence was one in 1200 adenoidectomies. Diagnoses included five submucous cleft palates, six occult submucous cleft palates, 22 cases of velopharyngeal disproportion, seven developmental or neurological causes, one iatrogenic palatal injury and one case that defied diagnosis. In six patients treatment was not required, 13 responded to speech therapy and 23 required surgical intervention. The choice of operation was based on the findings at investigation. Ten patients were treated by a superiorly based pharyngeal flap, 10 underwent a sphincteric pharyngoplasty and three had an intravelar veloplasty. Speech outcome was assessed in 36 cases. Treatment resulted in significantly improved speech in all but one patient and normal speech in 16 patients. Persistently altered speech is a rare complication of adenoidectomy. Preoperative screening by clinical examination will prevent some but not all of such problems. When patients present they should undergo multidisciplinary assessment and multi-modality investigation. A good outcome can be anticipated in most patients.

  4. NKT sublineage specification and survival requires the ubiquitin-modifying enzyme TNFAIP3/A20

    PubMed Central

    Verheugen, Eveline; Taghon, Tom; Lambrecht, Bart N.

    2016-01-01

    Natural killer T (NKT) cells are innate lymphocytes that differentiate into NKT1, NKT2, and NKT17 sublineages during development. However, the signaling events that control NKT sublineage specification and differentiation remain poorly understood. Here, we demonstrate that the ubiquitin-modifying enzyme TNFAIP3/A20, an upstream regulator of T cell receptor (TCR) signaling in T cells, is an essential cell-intrinsic regulator of NKT differentiation. A20 is differentially expressed during NKT cell development, regulates NKT cell maturation, and specifically controls the differentiation and survival of NKT1 and NKT2, but not NKT17, sublineages. Remaining A20-deficient NKT1 and NKT2 thymocytes are hyperactivated in vivo and secrete elevated levels of Th1 and Th2 cytokines after TCR ligation in vitro. Defective NKT development was restored by compound deficiency of MALT1, a key downstream component of TCR signaling in T cells. These findings therefore show that negative regulation of TCR signaling during NKT development controls the differentiation and survival of NKT1 and NKT2 cells. PMID:27551157

  5. The periodic down regulation of Cyclin E gene expression from exit of mitosis to end of G(1) is controlled by a deacetylase- and E2F-associated bipartite repressor element.

    PubMed

    Polanowska, J; Fabbrizio, E; Le Cam, L; Trouche, D; Emiliani, S; Herrera, R; Sardet, C

    2001-07-12

    The expression of cyclin E and that of a few other bona fide cell cycle regulatory genes periodically oscillates every cycle in proliferating cells. Although numerous experiments have documented the role of E2F sites and E2F activities in the control of these genes as cells exit from G(0) to move through the initial G(1)/S phase transition, almost nothing is known on the role of E2Fs during the subsequent cell cycles. Here we show that a variant E2F-site that is part of the Cyclin E Repressor Module (CERM) (Le Cam et al., 1999b) accounts for the periodic down regulation of the cyclin E promoter observed between the exit from mitosis until the mid/late G(1) phase in exponentially cycling cells. This cell cycle-dependent repression correlates with the periodic binding of an atypical G(1)-specific high molecular weight p107-E2F complex (Cyclin E Repressor Complex: CERC2) that differs in both size and DNA binding behaviors from known p107-E2F complexes. Notably, affinity purified CERC2 displays a TSA-sensitive histone deacetylase activity and, consistent with this, derepression of the cyclin E promoter by trichostatin A depends on the CERM element. Altogether, this shows that the cell cycle-dependent control of cyclin E promoter in cycling cells is embroiled in acetylation pathways via the CERM-like E2F element.

  6. A 20-KW Wind Energy Conversion System (WECS) at the Marine Corps Air Station, Kaneohe, Hawaii.

    DTIC Science & Technology

    1983-01-01

    NATIONAL BURLAU OF STANDARDS I963 A TN NO: N-1655 A 20-KW WIND ENERGY CONVERSION SYSTEM TITLE: (WECS) AT THE MARINE CORPS AI& STATION, KANEOHE, HAWAII...4 TITLE (o, S,,bIII1. S TYPE OF kEPORT II PERIOD COvERED A 20-KW WIND ENERGY CONVERSION SYSTEM Not final;Sep 78- Dec81 (WECS) AT THE MARINE CORPS AIR...from RepO) 18 SUPPLEMENTARY NOTES • -1 19 KEY WORDS eComf-Ur o, ,e . s d. it ,e f , &1d Ide-,fs by bd, umb,) Wind energy conversion systems, wind energy , wind

  7. 24 CFR 203.266 - Period covered by periodic MIP.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Period covered by periodic MIP. 203.266 Section 203.266 Housing and Urban Development Regulations Relating to Housing and...

  8. 24 CFR 203.266 - Period covered by periodic MIP.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER... 24 Housing and Urban Development 2 2013-04-01 2013-04-01 false Period covered by periodic MIP. 203.266 Section 203.266 Housing and Urban Development Regulations Relating to Housing and...

  9. 24 CFR 203.266 - Period covered by periodic MIP.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Period covered by periodic MIP. 203.266 Section 203.266 Housing and Urban Development Regulations Relating to Housing and...

  10. 24 CFR 203.266 - Period covered by periodic MIP.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER... 24 Housing and Urban Development 2 2012-04-01 2012-04-01 false Period covered by periodic MIP. 203.266 Section 203.266 Housing and Urban Development Regulations Relating to Housing and...

  11. 24 CFR 203.266 - Period covered by periodic MIP.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false Period covered by periodic MIP. 203.266 Section 203.266 Housing and Urban Development Regulations Relating to Housing and...

  12. 7 CFR 929.106 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 929.106 Section 929.106 Agriculture... LONG ISLAND IN THE STATE OF NEW YORK Rules and Regulations § 929.106 Fiscal period. The fiscal period... include the period of August 1, through August 31, 1968. Thereafter, the fiscal period will begin on...

  13. 7 CFR 959.104 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 959.104 Section 959.104 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulations General § 959.104 Fiscal period. The fiscal period shall begin August 1 of each year and end...

  14. 7 CFR 953.9 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 953.9 Section 953.9 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... STATES Order Regulating Handling Definitions § 953.9 Fiscal period. Fiscal period means the...

  15. Maternal Dietary Restriction During the Periconceptional Period in Normal-Weight or Obese Ewes Results in Adrenocortical Hypertrophy, an Up-Regulation of the JAK/STAT and Down-Regulation of the IGF1R Signaling Pathways in the Adrenal of the Postnatal Lamb

    PubMed Central

    Zhang, Song; Morrison, Janna L.; Gill, Amreet; Rattanatray, Leewen; MacLaughlin, Severence M.; Kleemann, David; Walker, Simon K.

    2013-01-01

    Maternal dietary restriction during the periconceptional period results in an increase in adrenal growth and in the cortisol stress response in the offspring. The intraadrenal mechanisms that result in the programming of these changes are not clear. Activation of the IGF and the signal transducer and activator of transcription (STAT)/suppressors of cytokine signaling (SOCS) pathways regulate adrenal growth. We have used an embryo transfer model in sheep to investigate the impact of exposure to either dietary restriction in normal or obese mothers or to maternal obesity during the periconceptional period on adrenal growth and function in the offspring. We assessed the adrenal abundance of key signaling molecules in the IGF-I and Janus kinase/STAT/SOCS pathways including IGF-I receptor, IGF-II receptor, Akt, mammalian target of rapamycin, ribosomal protein S6, eukaryotic translation initiation factor 4E-binding protein 1, eukaryotic translation initiation factor 4E, STAT1, STAT3, STAT5, SOCS1, and SOCS3 in female and male postnatal lambs. Maternal dietary restriction in the periconceptional period resulted in the hypertrophy of the adrenocortical cells in the zona fasciculata-reticularis and an up-regulation in STAT1, phospho-STAT1, and phospho-STAT3 (Ser727) abundance and a down-regulation in IGF-I receptor, Akt, and phospho-Akt abundance in the adrenal cortex of the postnatal lamb. These studies highlight that weight loss around the time of conception, independent of the starting maternal body weight, results in the activation of the adrenal Janus kinase/STAT pathway and adrenocortical hypertrophy. Thus, signals of adversity around the time of conception have a long-term impact on the mechanisms that regulate adrenocortical growth. PMID:24108072

  16. Maternal dietary restriction during the periconceptional period in normal-weight or obese ewes results in adrenocortical hypertrophy, an up-regulation of the JAK/STAT and down-regulation of the IGF1R signaling pathways in the adrenal of the postnatal lamb.

    PubMed

    Zhang, Song; Morrison, Janna L; Gill, Amreet; Rattanatray, Leewen; MacLaughlin, Severence M; Kleemann, David; Walker, Simon K; McMillen, I Caroline

    2013-12-01

    Maternal dietary restriction during the periconceptional period results in an increase in adrenal growth and in the cortisol stress response in the offspring. The intraadrenal mechanisms that result in the programming of these changes are not clear. Activation of the IGF and the signal transducer and activator of transcription (STAT)/suppressors of cytokine signaling (SOCS) pathways regulate adrenal growth. We have used an embryo transfer model in sheep to investigate the impact of exposure to either dietary restriction in normal or obese mothers or to maternal obesity during the periconceptional period on adrenal growth and function in the offspring. We assessed the adrenal abundance of key signaling molecules in the IGF-I and Janus kinase/STAT/SOCS pathways including IGF-I receptor, IGF-II receptor, Akt, mammalian target of rapamycin, ribosomal protein S6, eukaryotic translation initiation factor 4E-binding protein 1, eukaryotic translation initiation factor 4E, STAT1, STAT3, STAT5, SOCS1, and SOCS3 in female and male postnatal lambs. Maternal dietary restriction in the periconceptional period resulted in the hypertrophy of the adrenocortical cells in the zona fasciculata-reticularis and an up-regulation in STAT1, phospho-STAT1, and phospho-STAT3 (Ser727) abundance and a down-regulation in IGF-I receptor, Akt, and phospho-Akt abundance in the adrenal cortex of the postnatal lamb. These studies highlight that weight loss around the time of conception, independent of the starting maternal body weight, results in the activation of the adrenal Janus kinase/STAT pathway and adrenocortical hypertrophy. Thus, signals of adversity around the time of conception have a long-term impact on the mechanisms that regulate adrenocortical growth.

  17. INTERIOR VIEW WITH CASTING MACHINE COOLING A 20' IRON PIPE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    INTERIOR VIEW WITH CASTING MACHINE COOLING A 20' IRON PIPE PRIOR TO EXTRACTION FROM CASTING MACHINE. - McWane Cast Iron Pipe Company, Pipe Casting Area, 1201 Vanderbilt Road, Birmingham, Jefferson County, AL

  18. Mitral valve repair for degenerative disease: a 20-year experience.

    PubMed

    Daneshmand, Mani A; Milano, Carmelo A; Rankin, J Scott; Honeycutt, Emily F; Swaminathan, Madhav; Shaw, Linda K; Smith, Peter K; Glower, Donald D

    2009-12-01

    Recent advances in surgical technique allow repair of most mitral valves with degenerative disease. However, few long-term data exist to support the superiority of repair versus prosthetic valve replacement, and repair could be limited by late durability or other problems. This study was designed to compare survival characteristics of mitral valve repair versus prosthetic replacement for degenerative disorders during a 20-year period. From 1986 to 2006, 2,580 patients underwent isolated mitral valve procedures (with or without coronary artery bypass grafting), with 989 classified as having degenerative origin. Of these, 705 received valve repair, and 284 had prosthetic valve replacement. Differences in baseline characteristics between groups were assessed, and unadjusted survival estimates were generated using Kaplan-Meier methods. Survival curves were examined after adjustment for differences in baseline profiles using a Cox model, and average adjusted survival differences were quantified by area under the curve methodology. Survival differences during 15 years of follow-up also were assessed with propensity matching. Baseline characteristics were similar, except for (variable: repair, replacement) age: 62 years, 68 years; concomitant coronary artery bypass grafting: 24%, 32%; ejection fraction: 0.51, 0.55; congestive heart failure: 68%, 43%; and preoperative arrhythmia: 11%, 7% (all p < 0.05). Long-term survival was significantly better in the repair group, both for unadjusted data (p < 0.001) and for risk-adjusted results (p = 0.040). Patient survival in the course of 15 years averaged 7.3% better with repair, and increased with time of follow-up: 0.7% better for 0 to 5 years, 4.9% better for 5 to 10 years, and 21.3% better for 10 to 15 years. Treatment interaction between repair or replacement and age was negative (p = 0.66). In the propensity analysis, survival advantages of repair versus replacement were similar in magnitude with a p value of 0.046. As

  19. Alternative expression pattern of MALT1-A20-NF-κB in patients with rheumatoid arthritis.

    PubMed

    Wang, Xu; Zhu, Lihua; Liao, Ziwei; Zhang, Fan; Xu, Ling; Xu, Yan; Chen, Shaohua; Yang, Lijian; Zhou, Yi; Li, Yangqiu

    2014-01-01

    Rheumatoid arthritis (RA) is an inflammatory autoimmune disorder; abnormal T cell immunity plays a critical role in the development of RA. Recently, A20 was identified as a key negative regulator for T cell activation and inflammatory signaling and may be involved in RA pathogenesis. In this study, we analyzed the expression level of A20, NF-κB, and A20 regulatory factor mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) in patients with RA. Real-time PCR was used to determine the expression level of MALT1, MALT-V1, A20, and NF-κB genes in RA and healthy individuals (HI). Significantly lower A20 expression was found in RA patients compared with those in the healthy group, while NF-κB overexpression could be detected in patients with RA. Moreover, the MALT1 and MALT1-V1 expression level was downregulated in RA patients. A positive correlation between MALT1 and A20 and MALT1-V1 and A20 was found in patients with RA, and a tendency towards a negative correlation was found between MALT1 and NF-κB, MALT1-V1 and NF-κB, and A20 and NF-κB. In conclusion, we first characterized the alternative expression pattern of MALT1, A20, and NF-κB in RA, which may be related to abnormal T cell activation.

  20. Novel anti-apoptotic mechanism of A20 through targeting ASK1 to suppress TNF-induced JNK activation.

    PubMed

    Won, M; Park, K A; Byun, H S; Sohn, K-C; Kim, Y-R; Jeon, J; Hong, J H; Park, J; Seok, J H; Kim, J M; Yoon, W-H; Jang, I-S; Shen, H M; Liu, Z G; Hur, G M

    2010-12-01

    The zinc-finger protein A20 has crucial physiological functions as a dual inhibitor of nuclear factor-κB (NF-κB) activation and apoptosis in tumor necrosis factor (TNF) receptor 1 signaling pathway. Although the molecular basis for the anti-NF-κB function of A20 has been well elucidated, the anti-apoptotic function of A20 is largely unknown. Here, we report a novel mechanism underlying the anti-apoptotic function of A20: A20 blocks TNF-induced apoptosis through suppression of c-jun N-terminal kinase (JNK) by targeting apoptosis signal-regulating kinase1 (ASK1). First, the ectopic expression of A20 drastically inhibits TNF-induced JNK activation and apoptosis in multiple cell types including those deficient of NF-κB activation. Unexpectedly, the blunting effect of A20 on TNF-induced JNK activation is not mediated by affecting the TNFR1 signaling complex formation. Instead, A20 interacts with ASK1, an important MAPKK kinase in the JNK signaling cascade. More importantly, overexpression of wild-type A20, but not of mutant A20 (ZnF4; C624A, C627A), promotes degradation of the ASK1 through the ubiquitin-proteasome system. Taken together, the results from this study reveal a novel anti-apoptotic mechanism of A20 in TNF signaling pathway: A20 binds to ASK1 and mediates ASK1 degradation, leading to suppression of JNK activation and eventually blockage of apoptosis.

  1. 7 CFR 916.7 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 916.7 Section 916.7 Agriculture... Regulating Handling Definitions § 916.7 Fiscal period. Fiscal period is synonymous with fiscal year and means the 12-month period beginning on March 1 of one year and ending on the last day of February of the...

  2. 7 CFR 926.5 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 926.5 Section 926.5 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... period. Fiscal period is synonymous with fiscal year and crop year and means the 12-month period...

  3. 7 CFR 929.6 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 929.6 Section 929.6 Agriculture... LONG ISLAND IN THE STATE OF NEW YORK Order Regulating Handling Definitions § 929.6 Fiscal period. Fiscal period is synonymous with fiscal year and crop year and means the 12-month period beginning...

  4. 7 CFR 945.12 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 945.12 Section 945.12 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Fiscal period. Fiscal period means the period beginning and ending on the dates approved by the...

  5. 7 CFR 947.9 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 947.9 Section 947.9 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Definitions § 947.9 Fiscal period. Fiscal period means the period beginning and ending on the dates...

  6. 7 CFR 948.103 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 948.103 Section 948.103 Agriculture... Rules and Regulations General § 948.103 Fiscal period. Pursuant to § 948.10, the fiscal periods for each... following year, both dates inclusive. The 1986-87 fiscal period which began July 1, 1986, will be...

  7. 7 CFR 953.122 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 953.122 Section 953.122 Agriculture... STATES Rules and Regulations Change in Date for Completing Nominations, Term of Office, and Fiscal Period § 953.122 Fiscal period. The fiscal period, pursuant to § 953.9, which began on April 1, 1976, shall...

  8. 7 CFR 956.113 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 956.113 Section 956.113 Agriculture... VALLEY OF SOUTHEAST WASHINGTON AND NORTHEAST OREGON Rules and Regulations § 956.113 Fiscal period. Pursuant to § 956.13, fiscal period shall mean the period beginning January 1 and ending December 31...

  9. 7 CFR 958.12 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 958.12 Section 958.12 Agriculture... COUNTIES IN IDAHO, AND MALHEUR COUNTY, OREGON Order Regulating Handling Definitions § 958.12 Fiscal period. Fiscal period means the period beginning and ending on the dates approved by the Secretary pursuant...

  10. Progress Report for DOE DE-FG03-98ER20317 ''Regulation of the floral homeotic gene AGAMOUS'' Current and Final Funding Period: September 1, 2002, to December 31, 2002

    SciTech Connect

    Weigel, D.

    2003-03-11

    OAK-B135 Results obtained during this funding period: (1) Phylogenetic footprinting of AG regulatory sequences Sequences necessary and sufficient for AGAMOUS (AG) expression in the center of Arabidopsis flowers are located in the second intron, which is about 3 kb in size. This intron contains binding sites for two transcription factors, LEAFY (LFY) and WUSCHEL (WUS), which are direct activators of AG. We used the new method of phylogenetic shadowing to identify new regulatory elements. Among 29 Brassicaceae, several other motifs, but not the LFY and WUS binding sites previously identified, are largely invariant. Using reporter gene analyses, we tested six of these motifs and found that they are all functionally important for activity of AG regulatory sequences in A. thaliana. (2) Repression of AG by MADS box genes A candidate for repressing AG in the shoot apical meristem has been the MADS box gene FUL, since it is expressed in the shoot apical meristem and since an activated version (FUL:VP16) leads to ectopic AG expression in the shoot apical meristem. However, there is no ectopic AG expression in full single mutants. We therefore started to generate VP16 fusions of several other MADS box genes expressed in the shoot apical meristem, to determine which of these might be candidates for FUL redundant genes. We found that AGL6:VP16 has a similar phenotype as FUL:VP16, suggesting that AGL6 and FUL interact. We are now testing this hypothesis. (3) Two candidate AG regulators, WOW and ULA Because the phylogenetic footprinting project has identified several new candidate regulatory motifs, of which at least one (the CCAATCA motif) has rather strong effects, we had decided to put the analysis of WOW and ULA on hold, and to focus on using the newly identified motifs as tools. We conduct ed yeast one-hybrid screen with two of the conserved motifs, and identified several classes of transcription factors that can interact with them. One of these is encoded by the PAN gene

  11. Mucosal and systemic anti-HIV immunity controlled by A20 in mouse dendritic cells.

    PubMed

    Hong, Bangxing; Song, Xiao-Tong; Rollins, Lisa; Berry, Lindsey; Huang, Xue F; Chen, Si-Yi

    2011-02-01

    Both mucosal and systemic immune responses are required for preventing or containing HIV transmission and chronic infection. However, currently described vaccination approaches are largely ineffective in inducing both mucosal and systemic responses. In this study, we found that the ubiquitin-editing enzyme A20--an inducible feedback inhibitor of the TNFR, RIG-I, and TLR signaling pathways that broadly controls the maturation, cytokine production, and immunostimulatory potency of DCs--restricted systemically immunized DCs to induce both robust mucosal and systemic HIV-specific cellular and humoral responses. Mechanistic studies revealed that A20 regulated DC production of retinoic acid and proinflammatory cytokines, inhibiting the expression of gut-homing receptors on T and B cells. Furthermore, A20-silenced, hyperactivated DCs exhibited an enhanced homing capacity to draining and gut-associated lymphoid tissues (GALTs) after systemic administration. Thus, this study provides insights into the role of A20 in innate immunity. This work may allow the development of an efficient HIV vaccination strategy that is capable of inducing both robust systemic and mucosal anti-HIV cellular and humoral responses.

  12. Mucosal and systemic anti-HIV immunity controlled by A20 in mouse dendritic cells

    PubMed Central

    Hong, Bangxing; Song, Xiao-Tong; Rollins, Lisa; Berry, Lindsey; Huang, Xue F.; Chen, Si-Yi

    2011-01-01

    Both mucosal and systemic immune responses are required for preventing or containing HIV transmission and chronic infection. However, currently described vaccination approaches are largely ineffective in inducing both mucosal and systemic responses. In this study, we found that the ubiquitin-editing enzyme A20 — an inducible feedback inhibitor of the TNFR, RIG-I, and TLR signaling pathways that broadly controls the maturation, cytokine production, and immunostimulatory potency of DCs — restricted systemically immunized DCs to induce both robust mucosal and systemic HIV-specific cellular and humoral responses. Mechanistic studies revealed that A20 regulated DC production of retinoic acid and proinflammatory cytokines, inhibiting the expression of gut-homing receptors on T and B cells. Furthermore, A20-silenced, hyperactivated DCs exhibited an enhanced homing capacity to draining and gut-associated lymphoid tissues (GALTs) after systemic administration. Thus, this study provides insights into the role of A20 in innate immunity. This work may allow the development of an efficient HIV vaccination strategy that is capable of inducing both robust systemic and mucosal anti-HIV cellular and humoral responses. PMID:21206085

  13. Probability: Developing Student Intuition with a 20 by 20 Array.

    ERIC Educational Resources Information Center

    Kelly, Ivan W.; Bany, Bruce

    1984-01-01

    A random arrangement of two contrasting colors in a 20x20 array is used to facilitate students' understanding of the notions of randomness, independence, and long-run frequency. It can also be used to test some prevalent errors in probabilistic reasoning. Three activities are described. (MNS)

  14. Multicultural Counseling Competencies Research: A 20-Year Content Analysis

    ERIC Educational Resources Information Center

    Worthington, Roger L.; Soth-McNett, Angela M.; Moreno, Matthew V.

    2007-01-01

    The authors conducted a 20-year content analysis of the entire field of empirical research on the multicultural counseling competencies (D. W. Sue et al., 1982). They conducted an exhaustive search for empirical research articles using PsycINFO, as well as complete reviews of the past 20 years of several journals (e.g., Journal of Counseling…

  15. 7 CFR 906.15 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 906.15 Section 906.15 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... RIO GRANDE VALLEY IN TEXAS Order Regulating Handling Definitions § 906.15 Fiscal period. Fiscal...

  16. 7 CFR 958.112 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 958.112 Section 958.112 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... COUNTIES IN IDAHO, AND MALHEUR COUNTY, OREGON Rules and Regulations § 958.112 Fiscal period. The...

  17. Changes in mood status and neurotic levels during a 20-day bed rest

    NASA Astrophysics Data System (ADS)

    Ishizaki, Yuko; Ishizaki, Tatsuro; Fukuoka, Hideoki; Kim, Chang-Sun; Fujita, Masayo; Maegawa, Yuko; Fujioka, Hiroshi; Katsura, Taisaku; Suzuki, Yoji; Gunji, Atsuaki

    2002-04-01

    This study evaluated changes of mood status and depressive and neurotic levels in nine young male subjects during a 20-day 6° head-down tilting bed rest and examined whether exercise training modified these changes. Participants were asked to complete psychometrical inventories on before, during, and after the bed rest experiment. Depressive and neurotic levels were enhanced during bed rest period according to the Japanese version of Zung's Self-rating Depression Scale and the Japanese version of the General Health Questionnaire. Mood state "vigor" was impaired and "confusion" was increased during bed rest and recumbent control periods compared to pre-bed rest and ambulatory control periods according to the Japanese version of Profiles of Mood State, whereas the mood "tension-anxiety", "depression-dejection", "anger-hostility" and "fatigue" were relatively stable during experiment. Isometric exercise training did not modify these results. Microgravity, along with confinement to bed and isolation from familiar environments, induced impairment of mental status.

  18. Immune responsive gene 1 (IRG1) promotes endotoxin tolerance by increasing A20 expression in macrophages through reactive oxygen species.

    PubMed

    Li, Yingke; Zhang, Peng; Wang, Chengcai; Han, Chaofeng; Meng, Jun; Liu, Xingguang; Xu, Sheng; Li, Nan; Wang, Qingqing; Shi, Xueyin; Cao, Xuetao

    2013-06-07

    Sepsis-associated immunosuppression (SAIS) is regarded as one of main causes for the death of septic patients at the late stage because of the decreased innate immunity with a more opportunistic infection. LPS-tolerized macrophages, which are re-challenged by LPS after prior exposure to LPS, are regarded as the common model of hypo-responsiveness for SAIS. However, the molecular mechanisms of endotoxin tolerance and SAIS remain to be fully elucidated. In addition, negative regulation of the Toll-like receptor (TLR)-triggered innate inflammatory response needs further investigation. Here we show that expression of immune responsive gene 1 (IRG1) was highly up-regulated in the peripheral blood mononuclear cells of septic patients and in LPS-tolerized mouse macrophages. IRG1 significantly suppressed TLR-triggered production of proinflammatory cytokines TNF-α, IL-6, and IFN-β in LPS-tolerized macrophages, with the elevated expression of reactive oxygen species (ROS) and A20. Moreover, ROS enhanced A20 expression by increasing the H3K4me3 modification of histone on the A20 promoter domain, and supplement of the ROS abrogated the IRG1 knockdown function in breaking endotoxin tolerance by increasing A20 expression. Our results demonstrate that inducible IRG1 promotes endotoxin tolerance by increasing A20 expression through ROS, indicating a new molecular mechanism regulating hypoinflammation of sepsis and endotoxin tolerance.

  19. Neoplasia in immunosuppressed renal transplant patients: a 20-year experience

    SciTech Connect

    Krueger, T.C.; Tallent, M.B. Jr.; Richie, R.E.; Johnson, H.K.; MacDonell, R.C.; Turner, B.

    1985-05-01

    This review examines a 20-year experience in renal transplantation at our center to determine the effects of immunosuppression on the subsequent development of malignancies. Twenty patients had 21 malignancies from primary sites other than skin, yielding an incidence of 2.5%. There were 0.65 malignancies for each 100 cumulative patient years of immunosuppression. Suppression of the host immune response is associated with an increased incidence of malignancies.

  20. Attenuated A20 expression of acute myeloid leukemia-derived dendritic cells increased the anti-leukemia immune response of autologous cytolytic T cells.

    PubMed

    Zhang, Xiaoying; Su, Yongfeng; Song, Haifeng; Yu, Zhiyong; Zhang, Bin; Chen, Hu

    2014-06-01

    Previous studies reported leukemic cells from acute myeloid leukemia (AML) patients can differentiate into dendritic cells (DCs), which had some immunoregulatory dysfunctions to effectively stimulate autologous CTLs' anti-leukemia immune response. The zinc-finger protein A20, a negative regulator of the nuclear factor (NF)-κB pathway, was found to play a crucial role in controlling the maturation and function of human monocyte-derived DCs. However, the effects of A20 in AML derived DCs (AML-DCs) have not yet been evaluated. In this study, A20 expression was up-regulated in AML-DCs activated with tumor necrosis factor (TNF)-α. Then, A20 attenuation with siRNA in AML-DC enhanced the expression of several co-stimulatory molecules and proinflammatory cytokines. Furthermore, after A20 attenuation in AML-DCs, the autologous cytolytic T cells (CTLs) induced by AML-DCs had higher killing capability and specificity for primary AML cells. Additionally, receptor-interacting protein (RIP) and the NF-κBp65 pathway were elevated in AML-DCs when A20 was reduced. Hence, this study identified A20 as a negative regulator for controlling AML-DC maturation and immunostimulatory potency, as A20 down-regulation resulted in AML-DCs with enhanced autologous CTLs immune capacity through the NF-κB pathway.

  1. Interleukin-13 suppresses interleukin-10 via inhibiting A20 in peripheral B cells of patients with food allergy

    PubMed Central

    Linghu, En-qiang; Feng, Fan; Zhu, Bing; Wu, Cheng; Guo, Ming-zhou

    2016-01-01

    The regulatory B cells (Breg) are important in the body immunity. The differentiation process of Breg is not fully understood yet. Ubiquitin A20 has immune regulatory functions. This study aims to investigate the role of A20 in the regulation of interleukin (IL)-10 in B cells. In this study, B cells were isolated from the peripheral blood samples of healthy subjects and patients with food allergy (FA). The B cells were analyzed by flow cytometry, real time RT-PCR, Western blotting and chromatin immunoprecipitation. We observed that the frequency of Breg and the levels of A20 in B cells were markedly lower in FA patients than in healthy controls. In vitro deletion of A20 compromised the expression of IL-10. B cells in FA patients showed higher levels of histone deacetylase (HDAC)-11 than in healthy subjects. Exposure to IL-13 in the culture induced high levels of HDAC11 in B cells. IL-13 also repressed the expression of A20 in B cells, in which HDAC11 played a critical role via inducing the chromatin remoldeling at the IL-10 promoter locus. Mice with A20-deficient B cells are prone to FA. In summary, ubiquitin A20 can increase the IL-10 expression in B cells, which can be affected by the IL-13-induced HDAC11. To inhibit HDAC11 may have therapeutic potential for FA. PMID:27825134

  2. Inhibition of A20 expression in tumor microenvironment exerts anti-tumor effect through inducing myeloid-derived suppressor cells apoptosis

    PubMed Central

    Shao, Bin; Wei, Xiawei; Luo, Min; Yu, Jiayun; Tong, Aiping; Ma, Xuelei; Ye, Tinghong; Deng, Hongxin; Sang, Yaxiong; Liang, Xiao; Ma, Yu; Wu, Qinjie; Du, Wei; Du, Jing; Gao, Xiang; Wen, Yi; Fu, Ping; Shi, Huashan; Luo, Shuntao; Wei, Yuquan

    2015-01-01

    Myeloid-derived suppressor cells (MDSCs) are known to play important roles in the development of immunosuppressive tumor microenvironment. A20 is a zinc-finger protein which could negatively regulate apoptosis in several cell types. However, the role of A20 in tumor microenvironment remains largely unknown. In this study, we found that A20 was over-expressed in MDSCs. The treatment of tumor-bearing mice with small interfering RNA targeting A20 (si-A20) inhibited the growth of tumors. The infiltration of MDSCs was dramatically reduced after si-A20 treatment, as compared to control groups, whereas the numbers of dendritic cells and macrophages were not affected. Also, injection of si-A20 improved T cell mediated tumor-specific immune response. Depletion of MDSCs with anti-Gr1 antibody showed similar antitumor effect and improved T cell response. TNF-α was highly expressed after si-A20 injection. Furthermore, si-A20 induced apoptosis of MDSCs in the presence of TNF-α both in vivo and in vitro. Cleaved Caspase-3 and Caspase-8 were elevated with the activation of JNK pathway after the induction of MDSC apoptosis by si-A20. Thus, our findings suggested that knockdown of A20 in tumor site inhibited tumor growth at least through inducing the apoptosis of MDSCs. A20 might be a potential target in anticancer therapy. PMID:26561336

  3. IGF-1 deficiency in a critical period early in life influences the vascular aging phenotype in mice by altering miRNA-mediated post-transcriptional gene regulation: implications for the developmental origins of health and disease hypothesis.

    PubMed

    Tarantini, Stefano; Giles, Cory B; Wren, Jonathan D; Ashpole, Nicole M; Valcarcel-Ares, M Noa; Wei, Jeanne Y; Sonntag, William E; Ungvari, Zoltan; Csiszar, Anna

    2016-08-01

    Epidemiological findings support the concept of Developmental Origins of Health and Disease, suggesting that early-life hormonal influences during a sensitive period of development have a fundamental impact on vascular health later in life. The endocrine changes that occur during development are highly conserved across mammalian species and include dramatic increases in circulating IGF-1 levels during adolescence. The present study was designed to characterize the effect of developmental IGF-1 deficiency on the vascular aging phenotype. To achieve that goal, early-onset endocrine IGF-1 deficiency was induced in mice by knockdown of IGF-1 in the liver using Cre-lox technology (Igf1 (f/f) mice crossed with mice expressing albumin-driven Cre recombinase). This model exhibits low-circulating IGF-1 levels during the peripubertal phase of development, which is critical for the biology of aging. Due to the emergence of miRNAs as important regulators of the vascular aging phenotype, the effect of early-life IGF-1 deficiency on miRNA expression profile in the aorta was examined in animals at 27 months of age. We found that developmental IGF-1 deficiency elicits persisting late-life changes in miRNA expression in the vasculature, which significantly differed from those in mice with adult-onset IGF-1 deficiency (TBG-Cre-AAV8-mediated knockdown of IGF-1 at 5 month of age in Igf1 (f/f) mice). Using a novel computational approach, we identified miRNA target genes that are co-expressed with IGF-1 and associate with aging and vascular pathophysiology. We found that among the predicted targets, the expression of multiple extracellular matrix-related genes, including collagen-encoding genes, were downregulated in mice with developmental IGF-1 deficiency. Collectively, IGF-1 deficiency during a critical period during early in life results in persistent changes in post-transcriptional miRNA-mediated control of genes critical targets for vascular health, which likely contribute to

  4. Comparative distribution of protein components of the A20 ubiquitin-editing complex in normal human brain

    PubMed Central

    Pranski, Elaine L.; Van Sanford, Carson D.; Dalal, Nirjari V.; Orr, Adam L.; Karmali, Dipan; Cooper, Deborah S.; Costa, Nicole; Heilman, Craig J.; Gearing, Marla; Lah, James J.; Levey, Allan I.; Betarbet, Ranjita S.

    2012-01-01

    Activation of innate and adaptive immune responses is tightly regulated, as insufficient activation could result in defective clearance of pathogens, while excessive activation might lead to lethal systemic inflammation or autoimmunity. A20 functions as a negative regulator of innate and adaptive immunity by inhibiting NF-κB activation. A20 mediates its inhibitory function in a complex with other proteins including RNF11 and Itch, both E3 ubiquitin ligases and TAX1BP1, an adaptor protein. Since NF-κB has been strongly implicated in various neuronal functions, we predict that its inhibitor, the A20 complex, is also present in the nervous system. In efforts to better understand the role of A20 complex and NF-κB signaling pathway, we determined regional distribution of A20 mRNA as well as protein expression levels and distribution of RNF11, TAX1BP1 and Itch, in different brain regions. The distribution of TRAF6 was also investigated since TRAF6, also an E3 ligase, has an important role in NF-κB signaling pathway. Our investigations, for the first time, describe and demonstrate that the essential components of the A20 ubiquitin-editing complex are present and mainly expressed in neurons. The A20 complex components are also differentially expressed throughout the human brain. This study provides useful information about region specific expression of the A20 complex components that will be invaluable while determining the role of NF-κB signaling pathway in neuronal development and degeneration. PMID:22634524

  5. Recurrence of legionnaires disease at a hotel in the United States Virgin Islands over a 20-year period.

    PubMed

    Cowgill, Karen D; Lucas, Claressa E; Benson, Robert F; Chamany, Shadi; Brown, Ellen W; Fields, Barry S; Feikin, Daniel R

    2005-04-15

    We investigated 3 cases of legionnaires disease (LD) that developed in travelers who stayed at a hotel in the United States Virgin Islands where cases of LD occurred in 1981-1982 and in 1998. The temperature of the potable water at the hotel was in a range that could optimally support the growth of Legionella species, and the potable water was colonized with Legionella pneumophila in 1981-1982 and in 2002-2003.

  6. Changes in environmental tobacco smoke (ETS) exposure over a 20-year period: cross-sectional and longitudinal analyses.

    PubMed

    Jefferis, Barbara J; Thomson, Andrew G; Lennon, Lucy T; Feyerabend, Colin; Doig, Mira; McMeekin, Laura; Wannamethee, S Goya; Cook, Derek G; Whincup, Peter H

    2009-03-01

    To examine long-term changes in environmental tobacco smoke (ETS) exposure in British men between 1978 and 2000, using serum cotinine. Prospective cohort: British Regional Heart Study. General practices in 24 towns in England, Wales and Scotland. Non-smoking men: 2125 studied at baseline [questionnaire (Q1): 1978-80, aged 40-59 years], 3046 studied 20 years later (Q20: 1998-2000, aged 60-79 years) and 1208 studied at both times. Non-smokers were men reporting no current smoking with cotinine < 15 ng/ml at Q1 and/or Q20. Serum cotinine to assess ETS exposure. In cross-sectional analysis, geometric mean cotinine level declined from 1.36 ng/ml [95% confidence interval (CI): 1.31, 1.42] at Q1 to 0.19 ng/ml (95% CI: 0.18, 0.19) at Q20. The prevalence of cotinine levels < or = 0.7 ng/ml [associated with low coronary heart disease (CHD) risk] rose from 27.1% at Q1 to 83.3% at Q20. Manual social class and northern region of residence were associated with higher mean cotinine levels both at Q1 and Q20; older age was associated with lower cotinine level at Q20 only. Among 1208 persistent non-smokers, cotinine fell by 1.47 ng/ml (95% CI: 1.37, 1.57), 86% decline. Absolute falls in cotinine were greater in manual occupational groups, in the Midlands and Scotland compared to southern England, although percentage decline was very similar across groups. A marked decline in ETS exposure occurred in Britain between 1978 and 2000, which is likely to have reduced ETS-related disease risks appreciably before the introduction of legislation banning smoking in public places.

  7. Impact of the implementation of a vaccination strategy on hepatitis B virus infections in China over a 20-year period.

    PubMed

    Luo, Zhuanbo; Li, Lanjuan; Ruan, Bing

    2012-02-01

    Hepatitis B virus (HBV) vaccination has been recommended for all neonates in China since 1992. This article reviews the impact of HBV vaccination throughout the past 20 years in China. Before the introduction of the HBV vaccination program, approximately 9.8% of the general Chinese population tested positive for hepatitis B virus surface antigen (HBsAg). Since 1992, vaccination coverage has increased each year. In 1999, a National Expanded Programme on Immunization (EPI) review showed that the immunization coverage with three doses of HBV vaccine was 70.7%, and reached 99.0% in Beijing. The HBsAg carrier rate in the general population decreased to 7.2% in 2006. In particular, the prevalence of HBsAg decreased to 2.3% among children aged 5-14 years and to 1.0% among children younger than 5 years. In addition, the administration of the HBV vaccine may have reduced the risk of hepatocellular carcinoma among adults. Despite the administration of hepatitis B immunoglobulin and the HBV vaccine to children with HBsAg-positive mothers, the failure rate of HBV immunoprophylaxis was 5-10%. In China, vaccine failure was related to HBV S gene mutation and inadequate administration of HBV vaccine. The prevalence of HBV carriers in China was markedly reduced after the introduction of the universal HBV vaccination program. If we immunize all susceptible individuals with the hepatitis B vaccine (especially children), interrupt transmission, and provide antiviral treatment for existing HBV carriers, the number of new cases may be reduced to close to zero in the future and this may eventually result in the eradication of HBV. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  8. 30 CFR 725.14 - Grant periods.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Grant periods. 725.14 Section 725.14 Mineral... REGULATIONS REIMBURSEMENTS TO STATES § 725.14 Grant periods. The Director or his authorized designee shall normally approve a grant for a period of one year or less. OSM shall fund a program that extends over more...

  9. 30 CFR 725.14 - Grant periods.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Grant periods. 725.14 Section 725.14 Mineral... REGULATIONS REIMBURSEMENTS TO STATES § 725.14 Grant periods. The Director or his authorized designee shall normally approve a grant for a period of one year or less. OSM shall fund a program that extends over more...

  10. 42 CFR 136a.33 - Grace period.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Grace period. 136a.33 Section 136a.33 Public Health... HEALTH AND HUMAN SERVICES INDIAN HEALTH Transition Provisions § 136a.33 Grace period. (a) Upon the... of the new eligibility regulations) shall retain their eligibility for a six month grace period...

  11. 30 CFR 725.14 - Grant periods.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Grant periods. 725.14 Section 725.14 Mineral... REGULATIONS REIMBURSEMENTS TO STATES § 725.14 Grant periods. The Director or his authorized designee shall normally approve a grant for a period of one year or less. OSM shall fund a program that extends over more...

  12. 42 CFR 136a.31 - Transition period.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Transition period. 136a.31 Section 136a.31 Public... OF HEALTH AND HUMAN SERVICES INDIAN HEALTH Transition Provisions § 136a.31 Transition period. (a) The transition period for full implementation of the new eligibility regulations consists of three parts; (1) A...

  13. 14 CFR 325.6 - Periodic reviews.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Periodic reviews. 325.6 Section 325.6... REGULATIONS ESSENTIAL AIR SERVICE PROCEDURES § 325.6 Periodic reviews. (a) The Department will start a periodic review of essential air service within 1 year of the date of the previous determination of...

  14. 30 CFR 725.14 - Grant periods.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Grant periods. 725.14 Section 725.14 Mineral... REGULATIONS REIMBURSEMENTS TO STATES § 725.14 Grant periods. The Director or his authorized designee shall normally approve a grant for a period of one year or less. OSM shall fund a program that extends over...

  15. 7 CFR 930.107 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 930.107 Section 930.107 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Miscellaneous Provisions § 930.107 Fiscal period. Pursuant to § 930.7, fiscal period shall mean the...

  16. 7 CFR 947.114 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 947.114 Section 947.114 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Definitions § 947.114 Fiscal period. The fiscal period shall begin July 1 of each year and end June 30 of...

  17. 7 CFR 1205.307 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Fiscal period. 1205.307 Section 1205.307 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... Research and Promotion Order Definitions § 1205.307 Fiscal period. Fiscal period is the 12-month...

  18. 7 CFR 1250.303 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Fiscal period. 1250.303 Section 1250.303 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... Research and Promotion Order Definitions § 1250.303 Fiscal period. Fiscal period means the calendar...

  19. 7 CFR 945.111 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 945.111 Section 945.111 Agriculture... DESIGNATED COUNTIES IN IDAHO, AND MALHEUR COUNTY, OREGON Rules and Regulations Definitions § 945.111 Fiscal period. The fiscal period that began June 1, 1981, shall end July 31, 1982. Each year thereafter...

  20. 12 CFR 561.6 - Audit period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Audit period. 561.6 Section 561.6 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY DEFINITIONS FOR REGULATIONS AFFECTING ALL SAVINGS ASSOCIATIONS § 561.6 Audit period. The audit period of a savings association means the...

  1. A 20 GHz circularly polarized, fan beam slot array antenna

    NASA Astrophysics Data System (ADS)

    Weikle, D. C.

    1982-03-01

    An EHF waveguide slot array was developed for possible use as a receive-only paging antenna for ground mobile terminals. The design, fabrication, and measured performance of this antenna are presented. The antenna generates a circularly polarized fan beam that is narrow in azimuth and broad in elevation. When mechanically rotated in azimuth, it can receive a 20 GHz satellite transmission independent of mobile terminal direction. Azimuth plane sidelobe levels, which are typically <-40 dB from the main lobe, provide for discrimination against ground and airborne jammers.

  2. Intradural spinal meningioma in a 20-month-old female.

    PubMed

    Brusius, Carlos V; Pereira Filho, Arthur A; Barnewitz, João Paulo; Pütten, Antônio Carlos; Pitta Pinheiro, Claudio; Aesse, Flávio F

    2008-01-01

    Meningiomas in children account for less than 2% of all meningiomas, and their location in the spinal region is even less common. The authors present a case of a 20-month-old female who presented with lumbar back pain, neurogenic bladder and progressive paraparesis 6 months after she started to walk. Magnetic resonance imaging demonstrated an intradural extramedullary neoplasm extending from the tenth thoracic vertebra to the third lumbar vertebra. Complete excision of the tumor was performed by means of laminoplasty and the patient had a satisfactory postoperative recovery. Pathology and immunohistochemical studies diagnosed psammomatous meningioma.

  3. Absent menstrual periods - secondary

    MedlinePlus

    Amenorrhea - secondary; No periods - secondary; Absent periods - secondary; Absent menses - secondary; Absence of periods - secondary ... bleeding. When they stop taking these hormones, their periods may not return for more than 6 months. ...

  4. TNF phase III signalling in tolerant cells is tightly controlled by A20 and CYLD.

    PubMed

    Bikker, Rolf; Christmann, Martin; Preuß, Katharina; Welz, Bastian; Friesenhagen, Judith; Dittrich-Breiholz, Oliver; Huber, René; Brand, Korbinian

    2017-09-01

    Following the acute phase of an inflammatory reaction, a strictly controlled resolution of inflammation is necessary. A dysregulation of this process leads to hyperinflammation, chronic inflammatory disease, or immune paralysis. Different mechanisms participate in the coordinated termination of the inflammatory process, e.g. the expression of antiinflammatory molecules and different forms of tolerance. To better understand the processes which mediate resolution of TNF-dependent inflammation and induce tolerance, it is necessary to characterize the signal transduction quality during TNF long-term (pre)incubation. Within a time frame from 12 to 48h, designated as phase III of the TNF response, we measured an ongoing, constitutive activation of TNFR1/NF-κB-dependent pathways in monocytic cells. Phase III signalling which was also named "constitutive signaling in TNF tolerant cells" induces the expression of low- and high-sensitive target genes including A20 which is differentially regulated by transcriptional and proteolytic events. A20 strictly controls TNF long-term constitutive signalling in an IκB kinase complex- and partially RIP-dependent manner supported by adjuvant ABIN1. In addition, CYLD proteins participate in the regulation of this late-phase signal transduction, whereas downstream molecules such as Bcl3 and p50 are not involved. A20 and CYLD are expressed with different mRNA kinetics resulting in a strong or only a modest increase in protein levels, respectively. The identification of mechanisms which contribute to the termination of inflammation will provide additional diagnostic and therapeutic aspects to specifically diagnose certain aspects of inflammation and specifically modulate them. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Connectivity mapping (ssCMap) to predict A20-inducing drugs and their antiinflammatory action in cystic fibrosis

    PubMed Central

    Malcomson, Beth; Wilson, Hollie; Veglia, Eleonora; Thillaiyampalam, Gayathri; Barsden, Ruth; Donegan, Shauna; El Banna, Amal; Elborn, Joseph S.; Ennis, Madeleine; Kelly, Catriona; Zhang, Shu-Dong; Schock, Bettina C.

    2016-01-01

    Cystic fibrosis (CF) lung disease is characterized by chronic and exaggerated inflammation in the airways. Despite recent developments to therapeutically overcome the underlying functional defect in the cystic fibrosis transmembrane conductance regulator, there is still an unmet need to also normalize the inflammatory response. The prolonged and heightened inflammatory response in CF is, in part, mediated by a lack of intrinsic down-regulation of the proinflammatory NF-κB pathway. We have previously identified reduced expression of the NF-κB down-regulator A20 in CF as a key target to normalize the inflammatory response. Here, we have used publicly available gene array expression data together with a statistically significant connections’ map (sscMap) to successfully predict drugs already licensed for the use in humans to induce A20 mRNA and protein expression and thereby reduce inflammation. The effect of the predicted drugs on A20 and NF-κB(p65) expression (mRNA) as well as proinflammatory cytokine release (IL-8) in the presence and absence of bacterial LPS was shown in bronchial epithelial cells lines (16HBE14o−, CFBE41o−) and in primary nasal epithelial cells from patients with CF (Phe508del homozygous) and non-CF controls. Additionally, the specificity of the drug action on A20 was confirmed using cell lines with tnfαip3 (A20) knockdown (siRNA). We also show that the A20-inducing effect of ikarugamycin and quercetin is lower in CF-derived airway epithelial cells than in non-CF cells. PMID:27286825

  6. Evolution of periodicity in periodical cicadas.

    PubMed

    Ito, Hiromu; Kakishima, Satoshi; Uehara, Takashi; Morita, Satoru; Koyama, Takuya; Sota, Teiji; Cooley, John R; Yoshimura, Jin

    2015-09-14

    Periodical cicadas (Magicicada spp.) in the USA are famous for their unique prime-numbered life cycles of 13 and 17 years and their nearly perfectly synchronized mass emergences. Because almost all known species of cicada are non-periodical, periodicity is assumed to be a derived state. A leading hypothesis for the evolution of periodicity in Magicicada implicates the decline in average temperature during glacial periods. During the evolution of periodicity, the determinant of maturation in ancestral cicadas is hypothesized to have switched from size dependence to time (period) dependence. The selection for the prime-numbered cycles should have taken place only after the fixation of periodicity. Here, we build an individual-based model of cicadas under conditions of climatic cooling to explore the fixation of periodicity. In our model, under cold environments, extremely long juvenile stages lead to extremely low adult densities, limiting mating opportunities and favouring the evolution of synchronized emergence. Our results indicate that these changes, which were triggered by glacial cooling, could have led to the fixation of periodicity in the non-periodical ancestors.

  7. Evolution of periodicity in periodical cicadas

    PubMed Central

    Ito, Hiromu; Kakishima, Satoshi; Uehara, Takashi; Morita, Satoru; Koyama, Takuya; Sota, Teiji; Cooley, John R.; Yoshimura, Jin

    2015-01-01

    Periodical cicadas (Magicicada spp.) in the USA are famous for their unique prime-numbered life cycles of 13 and 17 years and their nearly perfectly synchronized mass emergences. Because almost all known species of cicada are non-periodical, periodicity is assumed to be a derived state. A leading hypothesis for the evolution of periodicity in Magicicada implicates the decline in average temperature during glacial periods. During the evolution of periodicity, the determinant of maturation in ancestral cicadas is hypothesized to have switched from size dependence to time (period) dependence. The selection for the prime-numbered cycles should have taken place only after the fixation of periodicity. Here, we build an individual-based model of cicadas under conditions of climatic cooling to explore the fixation of periodicity. In our model, under cold environments, extremely long juvenile stages lead to extremely low adult densities, limiting mating opportunities and favouring the evolution of synchronized emergence. Our results indicate that these changes, which were triggered by glacial cooling, could have led to the fixation of periodicity in the non-periodical ancestors. PMID:26365061

  8. A 20 MHz CMOS reorder buffer for a superscalar microprocessor

    NASA Technical Reports Server (NTRS)

    Lenell, John; Wallace, Steve; Bagherzadeh, Nader

    1992-01-01

    Superscalar processors can achieve increased performance by issuing instructions out-of-order from the original sequential instruction stream. Implementing an out-of-order instruction issue policy requires a hardware mechanism to prevent incorrectly executed instructions from updating register values. A reorder buffer can be used to allow a superscalar processor to issue instructions out-of-order and maintain program correctness. This paper describes the design and implementation of a 20MHz CMOS reorder buffer for superscalar processors. The reorder buffer is designed to accept and retire two instructions per cycle. A full-custom layout in 1.2 micron has been implemented, measuring 1.1058 mm by 1.3542 mm.

  9. Study of TTS for a 20-inch dynode PMT

    NASA Astrophysics Data System (ADS)

    Liao, Dong-Hao; Liu, Hong-Bang; Zhou, Yi-Xiong; Luo, Feng-Jiao; Wang, Zhi-Min; Yang, An-Bo; Xu, Mei-Hang; Xie, Wan; Qin, Zhong-Hua

    2017-07-01

    The neutrino detector for the Jiangmen Underground Neutrino Observatory (JUNO) requires a large number of photomultiplier tubes (PMTs), including 15000 MCP PMTs and 5000 dynode PMTs. The TTS (transit time spread) of the PMTs is very important for vertex and track reconstruction of the neutrinos in the detector. In this paper, we study the TTS of a 20-inch dynode PMT (R12860) from Hamamatsu for different high voltage, light intensity, light spot size and different photocathode regions. The impact from Earth’s magnetic field is also studied. The results achieved in this paper will be very useful for the JUNO experiment. Supported by Strategic Priority Research Program of the Chinese Academy of Sciences (XDA10011100) and National Natural Science Foundation of China (U1431109, 11265003)

  10. Autism: a "critical period" disorder?

    PubMed

    LeBlanc, Jocelyn J; Fagiolini, Michela

    2011-01-01

    Cortical circuits in the brain are refined by experience during critical periods early in postnatal life. Critical periods are regulated by the balance of excitatory and inhibitory (E/I) neurotransmission in the brain during development. There is now increasing evidence of E/I imbalance in autism, a complex genetic neurodevelopmental disorder diagnosed by abnormal socialization, impaired communication, and repetitive behaviors or restricted interests. The underlying cause is still largely unknown and there is no fully effective treatment or cure. We propose that alteration of the expression and/or timing of critical period circuit refinement in primary sensory brain areas may significantly contribute to autistic phenotypes, including cognitive and behavioral impairments. Dissection of the cellular and molecular mechanisms governing well-established critical periods represents a powerful tool to identify new potential therapeutic targets to restore normal plasticity and function in affected neuronal circuits.

  11. 8 CFR 245a.20 - Decisions, appeals, motions, and certifications.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... SECTION 245A OF THE IMMIGRATION AND NATIONALITY ACT Legal Immigration Family Equity (LIFE) Act... of applications. If the Service approves the application for adjustment of status under LIFE... tolled will not be accepted. The 30 day period for submitting an appeal begins 3 days after the NOD...

  12. Modifications of adiposity in school-age children according to nutritional status: a 20-year analysis.

    PubMed

    Ferrari, Tatiane K; Ferrari, Gerson Luis M; Silva Júnior, João Pedro da; Silva, Leonardo José da; Oliveira, Luís C; Matsudo, Victor K R

    2012-05-01

    To analyze adiposity changes in school-age children over a 20 year-period, according to nutritional status. The study is part of the Ilhabela Longitudinal Mixed Project on Growth, Development and Physical Fitness. A sample of 1,095 school students of both sexes, from 7 to 10 years, met the following inclusion criteria: (a) at least one complete assessment in one of the analyzed periods; (b) to be in prepubertal stage of sexual maturation; (c) to be apparently healthy. The periods analyzed were 1990/1991 (initial), 2000/2001 (10 years) and 2010/2011 (20 years). The variables analyzed were: body weight, height and adiposity through individual analysis of each skinfold. Children were classified as eutrophic, overweight and obese, according to the curves of body mass index for age and sex proposed by the World Health Organization. The statistical analysis used was one-way ANOVA, followed by Scheffé's post-hoc test, with p < 0.01. In boys, the largest increase occurred in the overweight group, followed by the obese and eutrophic groups. In girls, the largest increases occurred in the groups with overweight and eutrophic children, followed by the obese group. During the 20-year period analyzed, there were changes in adiposity, even when the nutritional status was controlled, showing that individuals who have similar body mass indexes may vary in proportion and distribution of subcutaneous adipose tissue. In both sexes, the increase was higher in the overweight group, and mainly in central skinfolds.

  13. Hyperkalemic periodic paralysis

    MedlinePlus

    Periodic paralysis - hyperkalemic; Familial hyperkalemic periodic paralysis; HyperKPP; HyperPP; Gamstorp disease ... factors include having other family members with periodic paralysis. It affects men more often than women.

  14. The Incidence of Primary Systemic Vasculitis in Jerusalem: A 20-year Hospital-based Retrospective Study.

    PubMed

    Nesher, Gideon; Ben-Chetrit, Eli; Mazal, Bracha; Breuer, Gabriel S

    2016-06-01

    The incidence of primary systemic vasculitides varies among different geographic regions and ethnic origins. The aim of this study was to examine the incidence rates of vasculitides in the Jerusalem Jewish population, and to examine possible trends in incidence rates over a 20-year period. The clinical databases of inpatients at the 2 medical centers in Jerusalem were searched for patients with vasculitis diagnosed between 1990-2009. Individual records were then reviewed by one of the authors. The significance of trends in incidence rates throughout the study period was evaluated by Pearson correlation coefficient. The average annual incidence rate of polyarteritis nodosa was 3.6/million adults (95% CI 1.6-4.7). Incidence rates did not change significantly during this period (r = 0.39, p = 0.088). The incidence of granulomatosis with polyangiitis (GPA) was 4.1 (2.2-5.9) for the whole period, during which it increased significantly (r = 0.53, p < 0.05). The incidence of microscopic polyangiitis (MPA) was lower: 2.3 (1.2-3.5)/million. It also increased significantly (r = 0.55, p < 0.05). The incidence of eosinophilic granulomatosis with polyangiitis was 1.2 (0.4-1.9), which remained stable throughout the study period. The incidence of Takayasu arteritis was 2.1/million (95% CI 1.2-2.9), and it also remained stable. Giant cell arteritis (GCA) incidence was 8.1 (5.7-10.6)/100,000 population aged 50 years or older. In sharp contrast with other vasculitides, its incidence decreased significantly throughout the study period (r = -0.61, p < 0.01). The incidence rates of vasculitides in the Jewish population of Jerusalem are in the lower range of global incidence rates. While GPA and MPA incidence are increasing, GCA incidence is decreasing.

  15. 14 CFR 271.8 - Rate period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... REGULATIONS GUIDELINES FOR SUBSIDIZING AIR CARRIERS PROVIDING ESSENTIAL AIR TRANSPORTATION § 271.8 Rate period... place essential air service level; or (5) The uncertainties of the market or other circumstances warrant... essential air service at the eligible place. ...

  16. 40 CFR 94.10 - Warranty period.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... EMISSIONS FROM MARINE COMPRESSION-IGNITION ENGINES General Provisions for Emission Regulations for Compression-Ignition Marine Engines § 94.10 Warranty period. (a)(1) Warranties imposed by § 94.1107...

  17. 40 CFR 94.10 - Warranty period.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... EMISSIONS FROM MARINE COMPRESSION-IGNITION ENGINES General Provisions for Emission Regulations for Compression-Ignition Marine Engines § 94.10 Warranty period. (a)(1) Warranties imposed by § 94.1107...

  18. 40 CFR 94.10 - Warranty period.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... EMISSIONS FROM MARINE COMPRESSION-IGNITION ENGINES General Provisions for Emission Regulations for Compression-Ignition Marine Engines § 94.10 Warranty period. (a)(1) Warranties imposed by § 94.1107...

  19. 40 CFR 94.10 - Warranty period.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... EMISSIONS FROM MARINE COMPRESSION-IGNITION ENGINES General Provisions for Emission Regulations for Compression-Ignition Marine Engines § 94.10 Warranty period. (a)(1) Warranties imposed by § 94.1107...

  20. 40 CFR 94.10 - Warranty period.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... EMISSIONS FROM MARINE COMPRESSION-IGNITION ENGINES General Provisions for Emission Regulations for Compression-Ignition Marine Engines § 94.10 Warranty period. (a)(1) Warranties imposed by § 94.1107...

  1. Vaginal bleeding between periods

    MedlinePlus

    ... periods; Intermenstrual bleeding; Spotting; Metrorrhagia Images Female reproductive anatomy Bleeding between periods Uterus References Bulun SE. The physiology and pathology of the female reproductive axis. In: ...

  2. Ground Testing A 20-Meter Inflation Deployed Solar Sail

    NASA Technical Reports Server (NTRS)

    Mann, Troy; Behun, Vaughn; Lichodziejewski, David; Derbes, Billy; Sleight, David

    2006-01-01

    Solar sails have been proposed for a variety of future space exploration missions and provide a cost effective source of propellantless propulsion. Solar sails span very large areas to capture and reflect photons from the Sun and are propelled through space by the transfer of momentum from the photons to the solar sail. The thrust of a solar sail, though small, is continuous and acts for the life of the mission without the need for propellant. Recent advances in materials and ultra-low mass gossamer structures have enabled a host of useful space exploration missions utilizing solar sail propulsion. The team of L Garde, NASA Jet Propulsion Laboratory (JPL), Ball Aerospace, and NASA Langley Research Center, under the direction of the NASA In-Space Propulsion Office (ISP), has been developing a scalable solar sail configuration to address NASA s future space propulsion needs. The 100-m baseline solar sail concept was optimized around the one astronomical unit (AU) Geostorm mission, and features a Mylar sail membrane with a striped-net sail suspension architecture with inflation-deployed sail support beams consisting of inflatable sub-Tg (glass transition temperature) rigidizable semi-monocoque booms and a spreader system. The solar sail has vanes integrated onto the tips of the support beams to provide full 3-axis control of the solar sail. This same structural concept can be scaled to meet the requirements of a number of other NASA missions. Static and dynamic testing of a 20m scaled version of this solar sail concept have been completed in the Space Power Facility (SPF) at the NASA Glenn Plum Brook facility under vacuum and thermal conditions simulating the operation of a solar sail in space. This paper details the lessons learned from these and other similar ground based tests of gossamer structures during the three year solar sail project.

  3. 48 CFR 4.704 - Calculation of retention periods.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Calculation of retention periods. 4.704 Section 4.704 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL ADMINISTRATIVE MATTERS Contractor Records Retention 4.704 Calculation of retention periods. (a) The...

  4. 17 CFR 285.2 - Periodic reports.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Periodic reports. 285.2 Section 285.2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS PURSUANT TO SECTION 15(a) OF THE BRETTON WOODS AGREEMENTS ACT § 285.2 Periodic reports. (a)...

  5. 17 CFR 285.2 - Periodic reports.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Periodic reports. 285.2 Section 285.2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS PURSUANT TO SECTION 15(a) OF THE BRETTON WOODS AGREEMENTS ACT § 285.2 Periodic reports. (a)...

  6. 17 CFR 285.2 - Periodic reports.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Periodic reports. 285.2 Section 285.2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS PURSUANT TO SECTION 15(a) OF THE BRETTON WOODS AGREEMENTS ACT § 285.2 Periodic reports. (a)...

  7. 29 CFR 1902.33 - Developmental period.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 5 2010-07-01 2010-07-01 false Developmental period. 1902.33 Section 1902.33 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Section 18(e) of the Act Completion of Developmental Steps-Certification § 1902.33 Developmental period...

  8. 24 CFR 221.775 - Option period.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Option period. 221.775 Section 221.775 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued... § 221.775 Option period. The mortgagee may exercise its option to assign within one year following the...

  9. 17 CFR 285.2 - Periodic reports.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Periodic reports. 285.2 Section 285.2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS PURSUANT TO SECTION 15(a) OF THE BRETTON WOODS AGREEMENTS ACT § 285.2 Periodic reports. (a)...

  10. 7 CFR 948.103 - Fiscal period.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Fiscal period. 948.103 Section 948.103 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... following year, both dates inclusive. The 1986-87 fiscal period which began July 1, 1986, will be...

  11. 45 CFR 1336.51 - Project period.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Project period. 1336.51 Section 1336.51 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES... NATIVE AMERICAN PROGRAMS Financial Assistance Provisions § 1336.51 Project period. The Notice of...

  12. 45 CFR 1336.51 - Project period.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 4 2014-10-01 2014-10-01 false Project period. 1336.51 Section 1336.51 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES... NATIVE AMERICAN PROGRAMS Financial Assistance Provisions § 1336.51 Project period. The Notice of...

  13. 45 CFR 1336.51 - Project period.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 4 2012-10-01 2012-10-01 false Project period. 1336.51 Section 1336.51 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES... NATIVE AMERICAN PROGRAMS Financial Assistance Provisions § 1336.51 Project period. The Notice of...

  14. 45 CFR 1336.51 - Project period.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 4 2011-10-01 2011-10-01 false Project period. 1336.51 Section 1336.51 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES... NATIVE AMERICAN PROGRAMS Financial Assistance Provisions § 1336.51 Project period. The Notice of...

  15. 45 CFR 1336.51 - Project period.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 4 2013-10-01 2013-10-01 false Project period. 1336.51 Section 1336.51 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES... NATIVE AMERICAN PROGRAMS Financial Assistance Provisions § 1336.51 Project period. The Notice of...

  16. 10 CFR 603.1295 - Periodic audit.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Periodic audit. 603.1295 Section 603.1295 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Definitions of Terms Used in this Part § 603.1295 Periodic audit. An audit of a participant, performed at an agreed-upon...

  17. 10 CFR 603.1295 - Periodic audit.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Periodic audit. 603.1295 Section 603.1295 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Definitions of Terms Used in this Part § 603.1295 Periodic audit. An audit of a participant, performed at an agreed-upon...

  18. 10 CFR 603.1295 - Periodic audit.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Periodic audit. 603.1295 Section 603.1295 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Definitions of Terms Used in this Part § 603.1295 Periodic audit. An audit of a participant, performed at an agreed-upon...

  19. 49 CFR 215.15 - Periodic inspection.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Periodic inspection. 215.15 Section 215.15 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS General § 215.15 Periodic inspection....

  20. 49 CFR 215.15 - Periodic inspection.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Periodic inspection. 215.15 Section 215.15 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS General § 215.15 Periodic inspection....

  1. 49 CFR 215.15 - Periodic inspection.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Periodic inspection. 215.15 Section 215.15 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS General § 215.15 Periodic inspection....

  2. 49 CFR 215.15 - Periodic inspection.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Periodic inspection. 215.15 Section 215.15 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS General § 215.15 Periodic inspection....

  3. 17 CFR 285.2 - Periodic reports.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Periodic reports. 285.2 Section 285.2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS PURSUANT TO SECTION 15(a) OF THE BRETTON WOODS AGREEMENTS ACT § 285.2 Periodic reports. (a)...

  4. 12 CFR 705.9 - Application period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Application period. 705.9 Section 705.9 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS COMMUNITY DEVELOPMENT REVOLVING LOAN PROGRAM FOR CREDIT UNIONS § 705.9 Application period. NCUA will announce annually...

  5. 5 CFR 316.304 - Trial period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS TEMPORARY AND TERM EMPLOYMENT Term Employment § 316.304 Trial period. (a) The first year of service of a term employee is a trial...) The agency may terminate a term employee at any time during the trial period. The employee is...

  6. Keratinocyte-specific ablation of the NF-κB regulatory protein A20 (TNFAIP3) reveals a role in the control of epidermal homeostasis.

    PubMed

    Lippens, S; Lefebvre, S; Gilbert, B; Sze, M; Devos, M; Verhelst, K; Vereecke, L; Mc Guire, C; Guérin, C; Vandenabeele, P; Pasparakis, M; Mikkola, M L; Beyaert, R; Declercq, W; van Loo, G

    2011-12-01

    The ubiquitin-editing enzyme A20 (tumor necrosis factor-α-induced protein 3) serves as a critical brake on nuclear factor κB (NF-κB) signaling. In humans, polymorphisms in or near the A20 gene are associated with several inflammatory disorders, including psoriasis. We show here that epidermis-specific A20-knockout mice (A20(EKO)) develop keratinocyte hyperproliferation, but no signs of skin inflammation, such as immune cell infiltration. However, A20(EKO) mice clearly developed ectodermal organ abnormalities, including disheveled hair, longer nails and sebocyte hyperplasia. This phenotype resembles that of mice overexpressing ectodysplasin-A1 (EDA-A1) or the ectodysplasin receptor (EDAR), suggesting that A20 negatively controls EDAR signaling. We found that A20 inhibited EDAR-induced NF-κB signaling independent from its de-ubiquitinating activity. In addition, A20 expression was induced by EDA-A1 in embryonic skin explants, in which its expression was confined to the hair placodes, known to be the site of EDAR expression. In summary, our data indicate that EDAR-induced NF-κB levels are controlled by A20, which functions as a negative feedback regulator, to assure proper skin homeostasis and epidermal appendage development.

  7. Lingual access for third molar surgery: a 20-year retrospective audit.

    PubMed

    Moss, C E; Wake, M J

    1999-08-01

    We describe a technique for obtaining lingual access for the insertion of a wide metal retractor to protect the lingual nerve from accidental damage during third molar surgery. We also report an audit of a single practice over a 20-year period using the technique described. The approach involves raising soft tissues on the lingual side of the lower third molar tooth to allow insertion of a broad Hovell's lingual retractor. We conclude that raising lingual tissues to form a wide tension-free flap and inserting a specifically designed retractor does not increase the incidence of lingual nerve morbidity. Indeed, the overall incidence of lingual nerve damage was particularly low compared with those in other published series.

  8. Altered expression of A20 gene in peripheral blood mononuclear cells is associated with the progression of chronic hepatitis B virus infection.

    PubMed

    Fan, Yu-Chen; Zhang, Yuan-Yuan; Sun, Yan-Yan; Wang, Na; Xiao, Xiao-Yan; Wang, Kai

    2016-10-18

    A20 is an important negative immune regulator but its role in chronic hepatitis B virus (HBV) infection is still unknown. This present study was to investigate the potential role of A20 gene in the progression of chronic HBV infection. A total of 236 chronic HBV patients were included and consisted of 63 hepatocellular carcinoma (HCC), 87 liver cirrhosis (LC) and 86 chronic hepatitis B (CHB). The mRNA level of A20 gene in peripheral blood mononuclear cells was determined using quantitative real-time polymerase chain reaction. Receptor operating characteristic curve (ROC) was performed to determine the diagnostic value of A20 mRNA in different stages of chronic HBV infection. A20 mRNA levels in all HBV patients were significantly higher than healthy controls (n=30), of whom HCC and LC patients showed higher A20 mRNA level than CHB patients. In CHB patients, A20 mRNA was closely associated with alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin. In LC patients, A20 mRNA was significantly associated with ALT, AST, albumin, haemoglobin and platelet. In HCC patients, elevated A20mRNA was also observed in patients with vascular invasion, liver cirrhosis and ascites, compared with those without. ROC analysis revealed that A20 mRNA could effectively discriminate LC from CHB, decompensated LC from compensated LC, and HCC from CHB. In conclusion, A20 mRNA expression in peripheral blood mononuclear cells was associated with dynamic progression of chronic HBV infection. A20 gene might be a potential biomarker to determine the different stages of chronic HBV infection.

  9. Cystic Fibrosis from Laboratory to Bedside: The Role of A20 in NF-κB-Mediated Inflammation.

    PubMed

    Bannon, Aidan; Zhang, Shu-Dong; Schock, Bettina C; Ennis, Madeleine

    2015-01-01

    Cystic fibrosis (CF) is a lifelong, inflammatory multi-organ disease and the most common lethal, genetic condition in Caucasian populations, with a median survival rate of 41.5 years. Pulmonary disease, characterized by infective exacerbations, bronchiectasis and increasing airway insufficiency is the most serious manifestation of this disease process, currently responsible for over 80% of CF deaths. Chronic dysregulation of the innate immune and host inflammatory response has been proposed as a mechanism central to this genetic condition, primarily driven by the nuclear factor κB (NF-κB) pathway. Chronic activation of this transcription factor complex leads to the production of pro-inflammatory cytokines and mediators such as IL-6, IL-8 and TNF-α. A20 has been described as a central and inducible negative regulator of NF-κB. This intracellular molecule negatively regulates NF-κB-driven pro-inflammatory signalling upon toll-like receptor activation at the level of TRAF6 activation. Silencing of A20 increases cellular levels of p65 and induces a pro-inflammatory state. We have previously shown that A20 expression positively correlates with lung function (FEV1%) in CF. Despite improvement in survival rates in recent years, advancements in available therapies have been incremental. We demonstrate that the experimental use of naturally occurring plant diterpenes such as gibberellin on lipopolysaccharide-stimulated cell lines reduces IL-8 release in an A20-dependent manner. We discuss how the use of a novel bio-informatics gene expression connectivity-mapping technique to identify small molecule compounds that similarly mimic the action of A20 may lead to the development of new therapeutic approaches capable of reducing chronic airway inflammation in CF.

  10. Your First Period

    MedlinePlus

    ... adult’s. Starting your menstrual period is one of these changes. What is a menstrual period? When puberty begins, your brain signals your body to produce hormones . Some of these hormones prepare your body each month for a ...

  11. Painful periods (dysmenorrhea) (image)

    MedlinePlus

    ... caused by hormone-induced uterine contractions before the period. Secondary dysmenorrhea may be caused by abnormal conditions ... serious conditions is present, the treatment for painful periods is pain relief. If a hormone imbalance is ...

  12. Period meter for reactors

    DOEpatents

    Rusch, Gordon K.

    1976-01-06

    An improved log N amplifier type nuclear reactor period meter with reduced probability for noise-induced scrams is provided. With the reactor at low power levels a sampling circuit is provided to determine the reactor period by measuring the finite change in the amplitude of the log N amplifier output signal for a predetermined time period, while at high power levels, differentiation of the log N amplifier output signal provides an additional measure of the reactor period.

  13. Sperm banking for fertility preservation: a 20-year experience.

    PubMed

    Johnson, Matrika D; Cooper, Amber R; Jungheim, Emily S; Lanzendorf, Susan E; Odem, Randall R; Ratts, Valerie S

    2013-09-01

    Sperm banking is an effective method to preserve fertility, but is not universally offered to males facing gonadotoxic treatment in the United States. We compared the disposition and semen parameters of cryopreserved sperm from individuals referred for sperm banking secondary to a cancer diagnosis to those of sperm from men banking for infertility reasons. We performed a retrospective cohort study that reviewed 1118 records from males who presented to bank sperm at Washington University between 1991 and 2010. We collected and analyzed demographics, semen parameters, and disposition of banked sperm. Four hundred and twenty-three men with cancer and 348 banking for infertility reasons attempted sperm cryopreservation in our unit during the specified time period. The most prevalent cancers in our cohort were testicular (32%), lymphoma (25%), and leukemia (11%). Patients with leukemia had the lowest pre-thaw counts and motility. Most cancer patients (57%) who banked elected to use, transfer to another facility, or keep their specimens in storage. The remaining samples were discarded electively (34%) or following death (8%). Overall semen parameters were similar between the cancer and infertility groups, but demographics, ability to bank a sample, azoospermia rates, length of storage, current banking status, and use of banked sperm differed significantly between the two groups. The majority of cancer patients who banked survived their cancer and chose to continue storage of banked samples. Cancer patients were more likely than infertility patients to use or continue storage of banked samples. Our study provides evidence that sperm banking is a utilized modality of fertility preservation in patients with a myriad of cancer diagnoses and should be offered to all men facing gonadotoxic therapies. Further work is needed to determine where disparities in access to sperm banking exist to improve the potential for future fertility in these males. Copyright © 2013 Elsevier

  14. Treatment of Pediatric Condylar Fractures: A 20-Year Experience

    PubMed Central

    Ghasemzadeh, Ali; Mundinger, Gerhard S.; Swanson, Edward W.; Utria, Alan F.; Dorafshar, Amir H.

    2016-01-01

    Background The purpose of this study was to define patterns of injury and treatment for condylar and subcondylar fractures and evaluate short-term outcomes in the pediatric population. Methods A retrospective chart review was performed on pediatric patients with mandibular condylar fractures who presented between 1990 and 2010. Computed tomographic imaging was reviewed for all patients to assess fracture characteristics. Mandibular fractures were codified using the Strasbourg Osteosynthesis Research Group and Lindahl classification methods. Results Sixty-four patients with 92 condylar fractures were identified. Of these patients, 29 had isolated condylar fracture and 35 had a condylar fracture associated with an additional mandibular arch fracture. The most common fracture patterns were diacapitular fracture in the Strasbourg Osteosynthesis Research Group system (n = 46) and vertical condylar head fracture in the Lindahl system (n = 14). Condylar fracture with additional mandibular arch fractures were treated with maxillomandibular fixation more often than patients with condylar fracture [n = 40 (74.1 percent) versus n = 14 (25.9 percent); p = 0.004]. No condylar fracture was treated in an open fashion. Forty-three patients returned for follow-up. The median follow-up period was 81 days (interquartile range, 35 to 294 days). Ten patients had complications (23.3 percent). The most common complication was malocclusion (n = 5). Nine of 10 patients with complications had condylar fracture with an additional mandibular arch fracture. Conclusions Closed treatment of condylar fractures yields satisfactory results in pediatric patients. Pediatric patients with condylar fractures combined with additional arch fractures experience a higher rate of unfavorable outcomes. PMID:26595021

  15. African Savanna-Forest Boundary Dynamics: A 20-Year Study.

    PubMed

    Cuni-Sanchez, Aida; White, Lee J T; Calders, Kim; Jeffery, Kathryn J; Abernethy, Katharine; Burt, Andrew; Disney, Mathias; Gilpin, Martin; Gomez-Dans, Jose L; Lewis, Simon L

    2016-01-01

    Recent studies show widespread encroachment of forest into savannas with important consequences for the global carbon cycle and land-atmosphere interactions. However, little research has focused on in situ measurements of the successional sequence of savanna to forest in Africa. Using long-term inventory plots we quantify changes in vegetation structure, above-ground biomass (AGB) and biodiversity of trees ≥10 cm diameter over 20 years for five vegetation types: savanna; colonising forest (F1), monodominant Okoume forest (F2); young Marantaceae forest (F3); and mixed Marantaceae forest (F4) in Lopé National Park, central Gabon, plus novel 3D terrestrial laser scanning (TLS) measurements to assess forest structure differences. Over 20 years no plot changed to a new stage in the putative succession, but F1 forests strongly moved towards the structure, AGB and diversity of F2 forests. Overall, savanna plots showed no detectable change in structure, AGB or diversity using this method, with zero trees ≥10 cm diameter in 1993 and 2013. F1 and F2 forests increased in AGB, mainly as a result of adding recruited stems (F1) and increased Basal Area (F2), whereas F3 and F4 forests did not change substantially in structure, AGB or diversity. Critically, the stability of the F3 stage implies that this stage may be maintained for long periods. Soil carbon was low, and did not show a successional gradient as for AGB and diversity. TLS vertical plant profiles showed distinctive differences amongst the vegetation types, indicating that this technique can improve ecological understanding. We highlight two points: (i) as forest colonises, changes in biodiversity are much slower than changes in forest structure or AGB; and (ii) all forest types store substantial quantities of carbon. Multi-decadal monitoring is likely to be required to assess the speed of transition between vegetation types.

  16. African Savanna-Forest Boundary Dynamics: A 20-Year Study

    PubMed Central

    Cuni-Sanchez, Aida; White, Lee J. T.; Calders, Kim; Jeffery, Kathryn J.; Abernethy, Katharine; Burt, Andrew; Disney, Mathias; Gilpin, Martin; Gomez-Dans, Jose L.; Lewis, Simon L.

    2016-01-01

    Recent studies show widespread encroachment of forest into savannas with important consequences for the global carbon cycle and land-atmosphere interactions. However, little research has focused on in situ measurements of the successional sequence of savanna to forest in Africa. Using long-term inventory plots we quantify changes in vegetation structure, above-ground biomass (AGB) and biodiversity of trees ≥10 cm diameter over 20 years for five vegetation types: savanna; colonising forest (F1), monodominant Okoume forest (F2); young Marantaceae forest (F3); and mixed Marantaceae forest (F4) in Lopé National Park, central Gabon, plus novel 3D terrestrial laser scanning (TLS) measurements to assess forest structure differences. Over 20 years no plot changed to a new stage in the putative succession, but F1 forests strongly moved towards the structure, AGB and diversity of F2 forests. Overall, savanna plots showed no detectable change in structure, AGB or diversity using this method, with zero trees ≥10 cm diameter in 1993 and 2013. F1 and F2 forests increased in AGB, mainly as a result of adding recruited stems (F1) and increased Basal Area (F2), whereas F3 and F4 forests did not change substantially in structure, AGB or diversity. Critically, the stability of the F3 stage implies that this stage may be maintained for long periods. Soil carbon was low, and did not show a successional gradient as for AGB and diversity. TLS vertical plant profiles showed distinctive differences amongst the vegetation types, indicating that this technique can improve ecological understanding. We highlight two points: (i) as forest colonises, changes in biodiversity are much slower than changes in forest structure or AGB; and (ii) all forest types store substantial quantities of carbon. Multi-decadal monitoring is likely to be required to assess the speed of transition between vegetation types. PMID:27336632

  17. The Periodic Pyramid

    ERIC Educational Resources Information Center

    Hennigan, Jennifer N.; Grubbs, W. Tandy

    2013-01-01

    The chemical elements present in the modern periodic table are arranged in terms of atomic numbers and chemical periodicity. Periodicity arises from quantum mechanical limitations on how many electrons can occupy various shells and subshells of an atom. The shell model of the atom predicts that a maximum of 2, 8, 18, and 32 electrons can occupy…

  18. Community College Periodicals.

    ERIC Educational Resources Information Center

    Pederson, Eldor O.

    Drawing from an examination of community college periodicals, their availability and characteristics, the academic affiliations of contributing authors, and the topics of their articles, this paper discusses the minor role which community college periodicals appear to play. A list of 35 periodicals dealing primary with community college education…

  19. The Periodic Pyramid

    ERIC Educational Resources Information Center

    Hennigan, Jennifer N.; Grubbs, W. Tandy

    2013-01-01

    The chemical elements present in the modern periodic table are arranged in terms of atomic numbers and chemical periodicity. Periodicity arises from quantum mechanical limitations on how many electrons can occupy various shells and subshells of an atom. The shell model of the atom predicts that a maximum of 2, 8, 18, and 32 electrons can occupy…

  20. The RING ubiquitin E3 RNF114 interacts with A20 and modulates NF-κB activity and T-cell activation

    PubMed Central

    Rodriguez, M S; Egaña, I; Lopitz-Otsoa, F; Aillet, F; Lopez-Mato, M P; Dorronroso, A; Lobato-Gil, S; Sutherland, J D; Barrio, R; Trigueros, C; Lang, V

    2014-01-01

    Accurate regulation of nuclear factor-κB (NF-κB) activity is crucial to prevent a variety of disorders including immune and inflammatory diseases. Active NF-κB promotes IκBα and A20 expression, important negative regulatory molecules that control the NF-κB response. In this study, using two-hybrid screening we identify the RING-type zinc-finger protein 114 (RNF114) as an A20-interacting factor. RNF114 interacts with A20 in T cells and modulates A20 ubiquitylation. RNF114 acts as negative regulator of NF-κB-dependent transcription, not only by stabilizing the A20 protein but also IκBα. Importantly, we demonstrate that in T cells, the effect of RNF114 is linked to the modulation of T-cell activation and apoptosis but is independent of cell cycle regulation. Altogether, our data indicate that RNF114 is a new partner of A2O involved in the regulation of NF-κB activity that contributes to the control of signaling pathways modulating T cell-mediated immune response. PMID:25165885

  1. 7 CFR 160.47 - Periodic re-inspection.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) NAVAL STORES REGULATIONS AND STANDARDS FOR NAVAL STORES Request Inspection by Licensed Inspectors § 160.47 Periodic re-inspection....

  2. 7 CFR 160.47 - Periodic re-inspection.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) NAVAL STORES REGULATIONS AND STANDARDS FOR NAVAL STORES Request Inspection by Licensed Inspectors § 160.47 Periodic re-inspection....

  3. Emotion Regulation in Parenthood

    PubMed Central

    Rutherford, Helena J.V.; Wallace, Norah S.; Laurent, Heidemarie K.; Mayes, Linda C.

    2015-01-01

    Emotion regulation, defined as the capacity to influence one’s experience and expression of emotion, is a complex skill now recognized to evolve throughout the lifetime. Here we examine the role of emotion regulation in parenthood, and propose that regulatory function during this period is distinct from the emotion regulation skills acquired and implemented during other periods of life. In this review, we consider the unique demands of caring for a child and recognize that parents have to maintain a regulated state as well as facilitate regulation in their child, especially early in development. We examine neurobiological, hormonal and behavioral shifts during the transition to parenthood that may facilitate parental regulation in response to infant cues. Furthermore, we consider how parents shape emotion regulation in their child, and the clinical implications of regulatory functioning within the parent-child relationship. PMID:26085709

  4. Role of Vaccinia Virus A20R Protein in DNA Replication: Construction and Characterization of Temperature-Sensitive Mutants

    PubMed Central

    Ishii, Koji; Moss, Bernard

    2001-01-01

    Previous analyses of randomly generated, temperature-sensitive vaccinia virus mutants led to the mapping of DNA synthesis negative complementation groups to the B1R, D4R, D5R, and E9L genes. Evidence from the yeast two-hybrid system that the D4R and D5R proteins can interact with the A20R protein suggested that A20R was also involved in DNA replication. We found that the A20R gene was transcribed early after infection, consistent with such a role. To investigate the function of the A20R protein, targeted mutations were made by substituting alanines for charged amino acids occurring in 11 different clusters. Four mutants were not isolated, suggesting that they were lethal, two mutants exhibited no temperature sensitivity, two mutants exhibited partial temperature sensitivity, and two mutants formed no plaques or infectious virus at 39°C. The two mutants with stringent phenotypes were further characterized. Temperature shift-up experiments indicated that the crucial period was between 6 and 12 h after infection, making it unlikely that the defect was in virus entry, early gene expression, or a late stage of virus assembly. Similar patterns of metabolically labeled viral early proteins were detected at permissive and nonpermissive temperatures, but one mutant showed an absence of late proteins under the latter conditions. Moreover, no viral DNA synthesis was detected when cells were infected with either stringent mutant at 39°C. The previous yeast two-hybrid analysis together with the present characterization of A20R temperature-sensitive mutants suggested that the A20R, D4R, and D5R proteins are components of a multiprotein DNA replication complex. PMID:11160663

  5. Quantum gates by periodic driving

    PubMed Central

    Shi, Z. C.; Wang, W.; Yi, X. X.

    2016-01-01

    Topological quantum computation has been extensively studied in the past decades due to its robustness against decoherence. One way to realize the topological quantum computation is by adiabatic evolutions—it requires relatively long time to complete a gate, so the speed of quantum computation slows down. In this work, we present a method to realize single qubit quantum gates by periodic driving. Compared to adiabatic evolution, the single qubit gates can be realized at a fixed time much shorter than that by adiabatic evolution. The driving fields can be sinusoidal or square-well field. With the sinusoidal driving field, we derive an expression for the total operation time in the high-frequency limit, and an exact analytical expression for the evolution operator without any approximations is given for the square well driving. This study suggests that the period driving could provide us with a new direction in regulations of the operation time in topological quantum computation. PMID:26911900

  6. A policy analysis of the introduction and dissemination of external peer review (visitatie) as a means of professional self-regulation amongst medical specialists in The Netherlands in the period 1985-2000.

    PubMed

    Lombarts, M J; Klazinga, N S

    2001-12-01

    By examining the introduction and dissemination of external peer review through site-visits (visitatie) amongst Dutch medical specialists, this paper sets out to deepen our insight into the dynamics of professional self-regulation and health care policy making. We explore how visitatie has been used in the political process between medical specialists and the state, serving as a strategy in protecting the autonomy of physicians. In the late eighties and early nineties, factors both internal as well as external to the medical profession all together determined the start and spread of visitatie. The conflict between state and doctors over the specialists' income, the introduction of the market oriented policies, new visions on quality assurance, the debate on the future of medical specialistic care and a new legal framework on quality assurance, challenged the medical community to find ways to reconfirm the public's trust in the self-regulating mechanism of the profession. One answer is found in carrying out 300-400 visitaties annually. During the past years, many stakeholders have perceived visitatie as a credible instrument in assuring quality patient care. The dynamics of professionalization and measurable impact of visitatie will determine whether or not it is here to stay.

  7. 24 CFR 203.261 - Calculation of periodic MIP.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Calculation of periodic MIP. 203.261 Section 203.261 Housing and Urban Development Regulations Relating to Housing and Urban...-Periodic Payment § 203.261 Calculation of periodic MIP. The amount of any periodic MIP shall be...

  8. A20 overexpression inhibits lipopolysaccharide-induced NF-κB activation, TRAF6 and CD40 expression in rat peritoneal mesothelial cells.

    PubMed

    Zou, Xun-Liang; Pei, De-An; Yan, Ju-Zhen; Xu, Gang; Wu, Ping

    2014-04-17

    Zinc finger protein A20 is a key negative regulator of inflammation. However, whether A20 may affect inflammation during peritoneal dialysis (PD)-associated peritonitis is still unclear. This study was aimed to investigate the effect of A20 overexpression on lipopolysaccharide (LPS)-induced inflammatory response in rat peritoneal mesothelial cells (RPMCs). Isolated and cultured RPMCs in vitro. Plasmid pGEM-T easy-A20 was transfected into RPMCs by Lipofectamine™2000. The protein expression of A20, phospho-IκBα, IκBα, TNF receptor-associated factor (TRAF) 6 and CD40 were analyzed by Western blot. The mRNA expression of TRAF6, CD40, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined by real time-PCR. NF-κB p65 DNA binding activity, IL-6 and TNF-α levels in cells culture supernatant were determined by ELISA. Our results revealed that RPMCs overexpression of A20 lead to significant decrease of LPS-induced IκBα phosphorylation and NF-κB DNA binding activity (all p<0.01). In addition, A20 also attenuated the expression of TRAF6, CD40, IL-6 and TNF-α as well as levels of IL-6 and TNF-α in cells culture supernatant (all p<0.05). However, A20 only partly inhibited CD40 expression. Our study indicated that A20 overexpression may depress the inflammatory response induced by LPS in cultured RPMCs through negatively regulated the relevant function of adaptors in LPS signaling pathway.

  9. Periodic chiral structures

    NASA Technical Reports Server (NTRS)

    Jaggard, Dwight L.; Engheta, Nader; Pelet, Philippe; Liu, John C.; Kowarz, Marek W.; Kim, Yunjin

    1989-01-01

    The electromagnetic properties of a structure that is both chiral and periodic are investigated using coupled-mode equations. The periodicity is described by a sinusoidal perturbation of the permittivity, permeability, and chiral admittance. The coupled-mode equations are derived from physical considerations and used to examine bandgap structure and reflected and transmitted fields. Chirality is observed predominantly in transmission, whereas periodicity is present in both reflection and transmission.

  10. Periodic Solutions of Spatially Periodic Hamiltonian Systems

    DTIC Science & Technology

    1989-07-10

    Theorem 0.2 generalizes Theorem 1.5 of Rabinowitz in [201. 3 Equation (0.1), under spatially periodic assumptions has been studied by several au...n x n symmetric matrix, H satisfying (HO), (H1) and (H2), and f = (0, fq) satisfying (fM), (fl) and (f2), Rabinowitz in [201 showed the existence of... Rabinowitz [17]. We consider a functional I : E x M ) R of class C’, where E is a Hilbert space and M is a compact manifold. Assuming that I satisfies a

  11. Periodic syndromes of childhood.

    PubMed

    Arav-Boger, R; Spirer, Z

    1997-01-01

    Periodic syndromes of childhood comprise a large group of disorders that require long-term follow-up to be diagnosed. Several disorders have fixed rhythmicity and are therefore identified more easily. Other disorders are usually diagnosed after a prolonged follow-up and exclusion of other more common childhood diseases. In general, most of the periodic fever syndromes have a benign prognosis, and their symptomatology tends to improve in the long term. Periodic syndromes without fever or chronic pain syndromes constitute not only a diagnostic dilemma but also a therapeutic challenge. A general diagnostic approach to the periodic syndromes is outlined in Figure 1.

  12. Haemocytic periodicity and periodic disorders: Periodic neutropenia, thrombocytopenia, lymphocytosis and anaemia

    PubMed Central

    Reimann, Hobart A.

    1971-01-01

    Evidence has accumulated of rhythmic numerical oscillation of each of the blood cells either independently or in combinations. The cyclic changes originate in the marrow of some normal persons and animals without causing illness, and can be induced experimentally. In more than 100 reported instances, periodic oscillations of various cells were accompanied by respective episodes of the disorders named in the title. The disorders may be transitory but usually recur throughout life and occasionally are fatal. All resist therapy. Features in common suggest an interrelationship of the haemal disorders and other disparate heritable periodic diseases. Theoretically, the rhythms are regulated by ubiquitous, inherent, intracellular bioclocks controlled hypothalamically or neurohumorally in relation to a feedback mechanism. Reactions to long cycles are of greater clinical importance than disturbances arising from the circadian rhythm. PMID:4397784

  13. Emergence of the A20/ABIN-mediated inhibition of NF-κB signaling via modifying the ubiquitinated proteins in a basal chordate.

    PubMed

    Yuan, Shaochun; Dong, Xiangru; Tao, Xin; Xu, Liqun; Ruan, Jie; Peng, Jian; Xu, Anlong

    2014-05-06

    In the past decade, ubiquitination has been well documented to have multifaceted roles in regulating NF-κB activation in mammals. However, its function, especially how deubiquitinating enzymes balance the NF-κB activation, remains largely elusive in invertebrates. Investigating bbtA20 and its binding proteins, bbt A20-binding inhibitor of NF-κB (bbtABIN1) and bbtABIN2, in Chinese amphioxus Branchiostoma belcheri tsingtauense, we found that bbtABIN2 can colocalize and compete with bbt TNF receptor-associated factor 6 to connect the K63-linked polyubiquitin chains, whereas bbtABIN1 physically links bbtA20 to bbt NF-κB essential modulator (bbtNEMO) to facilitate the K48-linked ubiquitination of bbtNEMO. Similar to human A20, bbtA20 is a dual enzyme that removes the K63-linked polyubiquitin chains and builds the K48-linked polyubiquitin chains on bbt receptor-interacting serine/threonine protein kinase 1b, leading to the inhibition of NF-κB signaling. Our study not only suggests that ubiquitination is an ancient strategy in regulating NF-κB activation but also provides the first evidence, to our knowledge, for ABINs/A20-mediated inhibition of NF-κB via modifying the ubiquitinated proteins in a basal chordate, adding information on the stepwise development of vertebrate innate immune signaling.

  14. 17 CFR 240.14a-20 - Shareholder approval of executive compensation of TARP recipients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... executive compensation of TARP recipients. 240.14a-20 Section 240.14a-20 Commodity and Securities Exchanges... § 240.14a-20 Shareholder approval of executive compensation of TARP recipients. If a solicitation is made by a registrant that is a TARP recipient, as defined in section 111(a)(3) of the...

  15. 17 CFR 240.14a-20 - Shareholder approval of executive compensation of TARP recipients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... executive compensation of TARP recipients. 240.14a-20 Section 240.14a-20 Commodity and Securities Exchanges... § 240.14a-20 Shareholder approval of executive compensation of TARP recipients. If a solicitation is made by a registrant that is a TARP recipient, as defined in section 111(a)(3) of the...

  16. 17 CFR 240.14a-20 - Shareholder approval of executive compensation of TARP recipients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... executive compensation of TARP recipients. 240.14a-20 Section 240.14a-20 Commodity and Securities Exchanges... § 240.14a-20 Shareholder approval of executive compensation of TARP recipients. If a solicitation is made by a registrant that is a TARP recipient, as defined in section 111(a)(3) of the...

  17. 17 CFR 240.14a-20 - Shareholder approval of executive compensation of TARP recipients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... executive compensation of TARP recipients. 240.14a-20 Section 240.14a-20 Commodity and Securities Exchanges... § 240.14a-20 Shareholder approval of executive compensation of TARP recipients. If a solicitation is made by a registrant that is a TARP recipient, as defined in section 111(a)(3) of the...

  18. The Living Periodic Table

    ERIC Educational Resources Information Center

    Nahlik, Mary Schrodt

    2005-01-01

    To help make the abstract world of chemistry more concrete eighth-grade students, the author has them create a living periodic table that can be displayed in the classroom or hallway. This display includes information about the elements arranged in the traditional periodic table format, but also includes visual real-world representations of the…

  19. The Living Periodic Table

    ERIC Educational Resources Information Center

    Nahlik, Mary Schrodt

    2005-01-01

    To help make the abstract world of chemistry more concrete eighth-grade students, the author has them create a living periodic table that can be displayed in the classroom or hallway. This display includes information about the elements arranged in the traditional periodic table format, but also includes visual real-world representations of the…

  20. Latent Period of Relaxation.

    PubMed

    Kobayashi, M; Irisawa, H

    1961-10-27

    The latent period of relaxation of molluscan myocardium due to anodal current is much longer than that of contraction. Although the rate and the grade of relaxation are intimately related to both the stimulus condition and the muscle tension, the latent period of relaxation remains constant, except when the temperature of the bathing fluid is changed.

  1. Multidimensional period doubling structures.

    PubMed

    Lee, Jeong Yup; Flom, Dvir; Ben-Abraham, Shelomo I

    2016-05-01

    This paper develops the formalism necessary to generalize the period doubling sequence to arbitrary dimension by straightforward extension of the substitution and recursion rules. It is shown that the period doubling structures of arbitrary dimension are pure point diffractive. The symmetries of the structures are pointed out.

  2. The tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20) imposes a brake on antitumor activity of CD8 T cells

    PubMed Central

    Giordano, Marilyn; Roncagalli, Romain; Bourdely, Pierre; Chasson, Lionel; Buferne, Michel; Yamasaki, Sho; Beyaert, Rudi; van Loo, Geert; Auphan-Anezin, Nathalie; Schmitt-Verhulst, Anne-Marie; Verdeil, Grégory

    2014-01-01

    The transcription factor NF-κB is central to inflammatory signaling and activation of innate and adaptive immune responses. Activation of the NF-κB pathway is tightly controlled by several negative feedback mechanisms, including A20, an ubiquitin-modifying enzyme encoded by the tnfaip3 gene. Mice with selective deletion of A20 in myeloid, dendritic, or B cells recapitulate some human inflammatory pathology. As we observed high expression of A20 transcripts in dysfunctional CD8 T cells in an autochthonous melanoma, we analyzed the role of A20 in regulation of CD8 T-cell functions, using mice in which A20 was selectively deleted in mature conventional T cells. These mice developed lymphadenopathy and some organ infiltration by T cells but no splenomegaly and no detectable pathology. A20-deleted CD8 T cells had increased sensitivity to antigen stimulation with production of large amounts of IL-2 and IFNγ, correlated with sustained nuclear expression of NF-κB components reticuloendotheliosis oncogene c-Rel and p65. Overexpression of A20 by retroviral transduction of CD8 T cells dampened their intratumor accumulation and antitumor activity. In contrast, relief from the A20 brake in NF-κB activation in adoptively transferred antitumor CD8 T cells led to improved control of melanoma growth. Tumor-infiltrating A20-deleted CD8 T cells had enhanced production of IFNγ and TNFα and reduced expression of the inhibitory receptor programmed cell death 1. As manipulation of A20 expression in CD8 T cells did not result in pathologic manifestations in the mice, we propose it as a candidate to be targeted to increase antitumor efficiency of adoptive T-cell immunotherapy. PMID:25024217

  3. The GH/IGF-1 axis in a critical period early in life determines cellular DNA repair capacity by altering transcriptional regulation of DNA repair-related genes: implications for the developmental origins of cancer.

    PubMed

    Podlutsky, Andrej; Valcarcel-Ares, Marta Noa; Yancey, Krysta; Podlutskaya, Viktorija; Nagykaldi, Eszter; Gautam, Tripti; Miller, Richard A; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2017-02-23

    Experimental, clinical, and epidemiological findings support the concept of developmental origins of health and disease (DOHAD), suggesting that early-life hormonal influences during a sensitive period around adolescence have a powerful impact on cancer morbidity later in life. The endocrine changes that occur during puberty are highly conserved across mammalian species and include dramatic increases in circulating GH and IGF-1 levels. Importantly, patients with developmental IGF-1 deficiency due to GH insensitivity (Laron syndrome) do not develop cancer during aging. Rodents with developmental GH/IGF-1 deficiency also exhibit significantly decreased cancer incidence at old age, marked resistance to chemically induced carcinogenesis, and cellular resistance to genotoxic stressors. Early-life treatment of GH/IGF-1-deficient mice and rats with GH reverses the cancer resistance phenotype; however, the underlying molecular mechanisms remain elusive. The present study was designed to test the hypothesis that developmental GH/IGF-1 status impacts cellular DNA repair mechanisms. To achieve that goal, we assessed repair of γ-irradiation-induced DNA damage (single-cell gel electrophoresis/comet assay) and basal and post-irradiation expression of DNA repair-related genes (qPCR) in primary fibroblasts derived from control rats, Lewis dwarf rats (a model of developmental GH/IGF-1 deficiency), and GH-replete dwarf rats (GH administered beginning at 5 weeks of age, for 30 days). We found that developmental GH/IGF-1 deficiency resulted in persisting increases in cellular DNA repair capacity and upregulation of several DNA repair-related genes (e.g., Gadd45a, Bbc3). Peripubertal GH treatment reversed the radiation resistance phenotype. Fibroblasts of GH/IGF-1-deficient Snell dwarf mice also exhibited improved DNA repair capacity, showing that the persisting influence of peripubertal GH/IGF-1 status is not species-dependent. Collectively, GH/IGF-1 levels during a critical period

  4. Monoplace hyperbaric chamber use of U.S. Navy Table 6: a 20-year experience.

    PubMed

    Weaver, L K

    2006-01-01

    We report a 20-year experience at LDS Hospital, Salt Lake City, UT using the U.S. Navy Treatment Table 6 (TT6) in an oxygen-filled monoplace hyperbaric chamber (1985-2004). Air breathing was provided via a demand regulator fitted with a SCUBA mouthpiece while the patient wore a nose clip. Intubated patients were mechanically ventilated with a Sechrist 500A ventilator, with a modified circuit providing air, when specified. We treated 90 patients: 72 divers (decompression sickness [DCS] = 67, arterial gas embolism [AGE] = 5), 10 hospital-associated AGE, and 8 miscellaneous conditions. They received a total of 118 TT6 (9 TT6 in intubated patients). Ninety-four percent of the TT6 schedules were tolerated and completed. The intolerance rate from two surveyed multiplace chambers was zero and 3% of 100 TT6 schedules each. Failure to complete the TT6 was due to oxygen toxicity (4) and claustrophobia (3). The U.S. Navy TT6 was well tolerated by patients with DCS or AGE treated in monoplace hyperbaric chambers, but tolerance may not be as high as when treated in the multiplace chamber.

  5. Deletion of the TNFAIP3/A20 gene detected by FICTION analysis in classical Hodgkin lymphoma

    PubMed Central

    2012-01-01

    Background The TNFAIP3 gene, which encodes a ubiquitin-modifying enzyme (A20) involved in the negative regulation of NF-κB signaling, is frequently inactivated by gene deletions/mutations in a variety of B-cell malignancies. However, the detection of this in primary Hodgkin lymphoma (HL) specimens is hampered by the scarcity of Hodgkin Reed-Sternberg (HR-S) cells even after enrichment by micro-dissection. Methods We used anti-CD30 immunofluorescence with fluorescence in-situ hybridization (FISH) to evaluate the relative number of TNFAIP3/CEP6 double-positive signals in CD30-positive cells. Results From a total of 47 primary classical Hodgkin lymphoma (cHL) specimens, 44 were evaluable. We found that the relative numbers of TNFAIP3/CD30 cells were distributed among three groups, corresponding to those having homozygous (11%), heterozygous (32%), and no (57%) deletions in TNFAIP3. This shows that TNFAIP3 deletions could be sensitively detected using our chosen methods. Conclusions Comparing the results with mutation analysis, TNFAIP3 inactivation was shown to have escaped detection in many samples with homozygous deletions. This suggests that TNFAIP3 inactivation in primary cHL specimens might be more frequent than previously reported. PMID:23039325

  6. Genealogy of periodic trajectories

    SciTech Connect

    de Adguiar, M.A.M.; Maldta, C.P.; de Passos, E.J.V.

    1986-05-20

    The periodic solutions of non-integrable classical Hamiltonian systems with two degrees of freedom are numerically investigated. Curves of periodic families are given in plots of energy vs. period. Results are presented for this Hamiltonian: H = 1/2(p/sub x//sup 2/ + p/sub y//sup 2/) + 1/2 x/sup 2/ + 3/2 y/sup 2/ - x/sup 2/y + 1/12 x/sup 4/. Properties of the families of curves are pointed out. (LEW)

  7. Periodically poled silicon

    NASA Astrophysics Data System (ADS)

    Hon, Nick K.; Tsia, Kevin K.; Solli, Daniel R.; Jalali, Bahram

    2009-03-01

    We propose a new class of photonic devices based on periodic stress fields in silicon that enable second-order nonlinearity as well as quasi-phase matching. Periodically poled silicon (PePSi) adds the periodic poling capability to silicon photonics and allows the excellent crystal quality and advanced manufacturing capabilities of silicon to be harnessed for devices based on second-order nonlinear effects. As an example of the utility of the PePSi technology, we present simulations showing that midwave infrared radiation can be efficiently generated through difference frequency generation from near-infrared with a conversion efficiency of 50%.

  8. 7 CFR 1210.530 - Retention period for records.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Retention period for records. 1210.530 Section 1210.530 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING... RESEARCH AND PROMOTION PLAN Rules and Regulations Records § 1210.530 Retention period for records. Each...

  9. 48 CFR 1816.405-272 - Award fee evaluation periods.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Award fee evaluation periods. 1816.405-272 Section 1816.405-272 Federal Acquisition Regulations System NATIONAL AERONAUTICS AND... Review, initial system test), establishing evaluation periods at conclusion of the milestones rather than...

  10. 48 CFR 452.211-74 - Period of Performance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Period of Performance. 452.211-74 Section 452.211-74 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Texts of Provisions and Clauses 452.211-74 Period...

  11. Setting the Periodic Table.

    ERIC Educational Resources Information Center

    Saturnelli, Annette

    1985-01-01

    Examines problems resulting from different forms of the periodic table, indicating that New York State schools use a form reflecting the International Union of Pure and Applied Chemistry's 1984 recommendations. Other formats used and reasons for standardization are discussed. (DH)

  12. The Periodic Table CD.

    ERIC Educational Resources Information Center

    Banks, Alton J.; Holmes, Jon L.

    1995-01-01

    Describes the characteristics of the digitized version of The Periodic Table Videodisc. Provides details about the organization of information and access to the data via Macintosh and Windows computers. (DDR)

  13. The Periodic Table CD.

    ERIC Educational Resources Information Center

    Banks, Alton J.; Holmes, Jon L.

    1995-01-01

    Describes the characteristics of the digitized version of The Periodic Table Videodisc. Provides details about the organization of information and access to the data via Macintosh and Windows computers. (DDR)

  14. Setting the Periodic Table.

    ERIC Educational Resources Information Center

    Saturnelli, Annette

    1985-01-01

    Examines problems resulting from different forms of the periodic table, indicating that New York State schools use a form reflecting the International Union of Pure and Applied Chemistry's 1984 recommendations. Other formats used and reasons for standardization are discussed. (DH)

  15. Suicide and Fire: A 20-Year Study of Self-Immolation Death in Sousse, Tunisia.

    PubMed

    Jedidi, Maher; Cherif El Khal, Mohamed; Mlayeh, Souheil; Masmoudi, Tasnim; Mahjoub, Mohamed; Yassine Brahem, Mohamed; Ben Dhiab, Mohamed; Zemni, Majed; Kamel Souguir, Mohamed

    2016-11-15

    Self-immolation is a self-destructive conduct described since antiquity. Its frequency is variable from one country to another and it is a real public health problem in parts of the world. In Tunisia, after the 2011 revolution the problem of self-immolation protest has been highly publicized giving the impression of an increase in this phenomenon. This is a retrospective analysis of all fatal self-immolation cases, collected over a 20-year period (1996-2015) at the Forensic Medicine Department of the Farhat Hached University Hospital, Sousse, Tunisia. A total of 41 cases were collected, of which 23 were men (56%). The mean age was 36.1 years. Prior to 2011, 78.9% of the victims of self-immolation were women and after 2011, 86.4% were men. The rural origin of the victims was found in 56.25% of the cases. History of psychiatric illness was found in four individuals. The self-immolation took place in the victims' homes in 19 cases (46.3%). It came after a conjugal or family conflict in 14 cases (34.1%) and it is of protest character in 8 cases (19.5%). This study confirmed the increasing frequency of self-immolation in Tunisia after the 2011 revolution and noted a change in the victims' profiles.

  16. Kaposi varicelliform eruption in patients with Darier disease: a 20-year retrospective study.

    PubMed

    Vogt, Kaitlin A; Lohse, Christine M; El-Azhary, Rokea A; Gibson, Lawrence E; Lehman, Julia S

    2015-03-01

    Kaposi varicelliform eruption (KVE), or herpes simplex virus (HSV) superinfection of pre-existing skin lesions, may complicate Darier disease. We sought to compare the clinical features and outcomes of patients with Darier disease who developed KVE superinfection with those who did not. A 20-year retrospective analysis of 79 patients with Darier disease treated at our institution was performed. Eleven (14%) patients developed KVE, of whom 45% required hospitalization for their skin disease during the follow-up period. Patients with KVE had more severe Darier disease (P = .030) and were more likely to be hospitalized (P = .015). HSV was detected in erosions without concomitant vesicles or pustules in 64% of confirmed cases. In all, 23 (55%) patients with erosions had HSV testing pursued. Retrospective study design is a limitation. The majority of KVE occurs in painless or painful erosions that may also appear impetiginized without vesicle or pustule formation. As HSV superinfection is correlated with severe Darier disease and risk for hospitalization, increased recognition of this phenomenon may lead to better patient outcomes. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  17. Trends in acoustic neuroma management: a 20-year review of the oxford skull base clinic.

    PubMed

    Mackeith, Samuel A C; Kerr, Richard S; Milford, Chris A

    2013-08-01

    Objective To describe the change in the management of acoustic neuromas at one United Kingdom center over a 20-year period and to compare this with what is known regarding trends in practice on a national and international scale. Design, Setting, and Participants Data was collected prospectively on all patients attending the Oxford Skull Base Clinic between 1990 and 2009. Main Outcome Measures The proportion of patients managed initially by observation versus radiotherapy versus surgery was recorded for each year. Results Significantly more patients received radiation treatment (instead of surgery) between 2000 and 2009 when compared with 1990 to 1999. Compared with national audit data, the Oxford Skull Base Clinic treats a higher proportion of patients with radiotherapy and significantly lower proportion with surgery, though the trend nationally is toward more observation and radiotherapy and less surgery. Conclusion Surgery will remain crucial in the management of some patients with acoustic neuromas (usually those with the larger tumors where radiosurgery is recognized to be less appropriate), but using current trends to predict future practice would suggest that alternative nonmicrosurgical treatment may play an increasingly important role in the future.

  18. Pneumocystis jiroveci pneumonia in rheumatic disease: a 20-year single-centre experience.

    PubMed

    Mecoli, Christopher A; Saylor, Deanna; Gelber, Allan C; Christopher-Stine, Lisa

    2017-01-01

    Pneumocystis jiroveci pneumonia (PJP) is an opportunistic infection with high mortality among patients with underlying rheumatologic conditions. Given the paucity of prospective data to guide treatment, clinical guidelines to initiate PJP prophylaxis are based on expert opinion and identify patients on ≥20 mg daily prednisone for ≥4 weeks duration for treatment. Herein we describe the PJP experience in rheumatic disease over a 20-year period at a single academic medical centre to investigate this 20 mg threshold and risk associated with lymphocyte counts, co-existing lung disease and immunosuppressive medications. We conducted a retrospective review of all admitted patients who received a PJP or PCP ICD-9 code (136.3) from January 1996 through October 2015. Twenty-one cases of confirmed PJP (by immunofluorescence or polymerase chain reaction) were reviewed, averaging to one case/year. The most common underlying rheumatologic conditions were inflammatory myopathy, lupus, and granulomatosis with polyangiitis. None of these 21 patients was receiving PJP prophylaxis upon admission. Eighteen (86%) were receiving ≥20 mg prednisone daily at the time of PJP diagnosis. Of the 3 treated with <20 mg prednisone, all received concomitant immunosuppressive medications, 2 with cyclophosphamide. Overall, there was a 43% (9/21) mortality rate. Immunosuppressant medication use, interstitial lung disease, or lymphocyte count did not impact mortality risk. PJP portends high mortality yet is a largely preventable complication of rheumatic disease treatment. Consideration to initiate prophylaxis should be made for patients exceeding the daily 20 mg prednisone threshold, and those receiving cyclophosphamide.

  19. Context-driven cocaine-seeking in abstinent rats increases activity-regulated gene expression in the basolateral amygdala and dorsal hippocampus differentially following short and long periods of abstinence.

    PubMed

    Hearing, M C; Schochet, T L; See, R E; McGinty, J F

    2010-10-13

    In this study, the expression patterns of zif268 and activity-regulated cytoskeleton-associated gene (arc) were investigated in the basolateral amygdala (BLA) and dorsal hippocampal (dHPC) subregions during context-induced drug-seeking following 22 h or 15 d abstinence from cocaine self-administration. Arc and zif/268 mRNA in BLA and dHPC increased after re-exposure to the cocaine-paired chamber at both timepoints; however, only the BLA increases (with one exception-see below) were differentially affected by the presence or absence of the cocaine-paired lever in the chamber. Following 22 h of abstinence, arc mRNA was significantly increased in the BLA of cocaine-treated rats re-exposed to the chamber only with levers extended, whereas following 15 d of abstinence, arc mRNA in the BLA was increased in cocaine-treated rats returned to the chamber with or without levers extended. In contrast, zif268 mRNA in the BLA was greater in cocaine-treated rats returned to the chamber with levers extended vs. levers retracted only after 15 d of abstinence. In the dentate gyrus (DG) following 22 h of abstinence, zif268 mRNA was greater in rats returned to the chamber where levers were absent regardless of drug treatment whereas arc mRNA was increased in CA1 (cell bodies and dendrites) and CA3 only in cocaine-treated groups. Following 15 d of abstinence, arc mRNA was significantly greater in CA1 and CA3 of both cocaine-treated groups returned to the chamber than in those placed into a familiar, non-salient alternate environment; however, only in CA1 cell bodies the cocaine context-induced increases significantly greater than in yoked-saline controls. In contrast, zif/268 mRNA in all dHPC regions was significantly greater in both cocaine-treated groups returned to the cocaine context than in the cocaine-treated group returned to an alternative environment or saline-treated groups. These data suggest that the temporal dynamics of arc and zif268 gene expression in the BLA and d

  20. 48 CFR 52.214-16 - Minimum Bid Acceptance Period.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Minimum Bid Acceptance Period. 52.214-16 Section 52.214-16 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... date specified in this solicitation for receipt of bids. (b) This provision supersedes any language...

  1. 48 CFR 252.247-7011 - Period of contract.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Period of contract. 252.247-7011 Section 252.247-7011 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of...

  2. 48 CFR 217.7103-2 - Period of agreement.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Period of agreement. 217.7103-2 Section 217.7103-2 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM.... (c) Cancellation of a master agreement does not affect the rights and liabilities under any job...

  3. 20 CFR 411.171 - When does the period of using a ticket end?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... ticket terminates if your outcome payment period ends); (b) The day before the effective date of a... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false When does the period of using a ticket end... Introduction § 411.171 When does the period of using a ticket end? The period of using a ticket ends with the...

  4. The transcription factor DREAM represses the deubiquitinase A20 and mediates inflammation.

    PubMed

    Tiruppathi, Chinnaswamy; Soni, Dheeraj; Wang, Dong-Mei; Xue, Jiaping; Singh, Vandana; Thippegowda, Prabhakar B; Cheppudira, Bopaiah P; Mishra, Rakesh K; Debroy, Auditi; Qian, Zhijian; Bachmaier, Kurt; Zhao, You-Yang; Christman, John W; Vogel, Stephen M; Ma, Averil; Malik, Asrar B

    2014-03-01

    Here we found that the transcription repressor DREAM bound to the promoter of the gene encoding A20 to repress expression of this deubiquitinase that suppresses inflammatory NF-κB signaling. DREAM-deficient mice displayed persistent and unchecked A20 expression in response to endotoxin. DREAM functioned by transcriptionally repressing A20 through binding to downstream regulatory elements (DREs). In contrast, binding of the transcription factor USF1 to the DRE-associated E-box domain in the gene encoding A20 activated its expression in response to inflammatory stimuli. Our studies define the critical opposing functions of DREAM and USF1 in inhibiting and inducing A20 expression, respectively, and thereby the strength of NF-κB signaling. Targeting of DREAM to induce USF1-mediated A20 expression is therefore a potential anti-inflammatory strategy for the treatment of diseases associated with unconstrained NF-κB activity, such as acute lung injury.

  5. 7 CFR 905.11 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 905.11 Section 905.11 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE ORANGES, GRAPEFRUIT, TANGERINES,...

  6. 32 CFR 552.80 - Suspension period.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 3 2010-07-01 2010-07-01 true Suspension period. 552.80 Section 552.80 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY MILITARY RESERVATIONS AND NATIONAL CEMETERIES REGULATIONS AFFECTING MILITARY RESERVATIONS Solicitation on Military Reservations §...

  7. 7 CFR 927.9 - Fiscal period.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Fiscal period. 927.9 Section 927.9 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE PEARS GROWN IN OREGON AND...

  8. 50 CFR 424.21 - Periodic review.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A LISTING ENDANGERED AND THREATENED SPECIES AND DESIGNATING CRITICAL HABITAT Revision of the Lists § 424.21 Periodic review. At least once every 5 years, the Secretary shall conduct a review of each listed species to determine whether it...

  9. 50 CFR 424.21 - Periodic review.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A LISTING ENDANGERED AND THREATENED SPECIES AND DESIGNATING CRITICAL HABITAT Revision of the Lists § 424.21 Periodic review. At least once every 5 years, the Secretary shall conduct a review of each listed species to determine whether it...

  10. 49 CFR 215.15 - Periodic inspection.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS General § 215.15 Periodic inspection. (a) After June 30, 1980, a railroad may not place or continue in service a freight car that has not received...

  11. 7 CFR 917.9 - Fiscal period.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Fiscal period. 917.9 Section 917.9 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE FRESH PEARS AND PEACHES GROWN...

  12. 7 CFR 917.9 - Fiscal period.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Fiscal period. 917.9 Section 917.9 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE FRESH PEARS AND PEACHES GROWN...

  13. 7 CFR 917.9 - Fiscal period.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Fiscal period. 917.9 Section 917.9 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE FRESH PEARS AND PEACHES GROWN...

  14. 7 CFR 917.9 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 917.9 Section 917.9 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE FRESH PEARS AND PEACHES GROWN...

  15. 7 CFR 917.9 - Fiscal period.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Fiscal period. 917.9 Section 917.9 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE FRESH PEARS AND PEACHES GROWN...

  16. 7 CFR 1212.7 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS..., PROMOTION, CONSUMER EDUCATION AND INDUSTRY INFORMATION ORDER Honey Packers and Importers Research, Promotion, Consumer Education, and Industry Information Order Definitions § 1212.7 Fiscal period. “Fiscal...

  17. 12 CFR 219.24 - Retention period.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... and Banking FEDERAL RESERVE SYSTEM BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM REIMBURSEMENT FOR PROVIDING FINANCIAL RECORDS; RECORDKEEPING REQUIREMENTS FOR CERTAIN FINANCIAL RECORDS (REGULATION S.... All records that are required to be retained by this subpart shall be retained for a period of five...

  18. 12 CFR 219.24 - Retention period.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... and Banking FEDERAL RESERVE SYSTEM BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM REIMBURSEMENT FOR PROVIDING FINANCIAL RECORDS; RECORDKEEPING REQUIREMENTS FOR CERTAIN FINANCIAL RECORDS (REGULATION S.... All records that are required to be retained by this subpart shall be retained for a period of five...

  19. 12 CFR 219.24 - Retention period.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... and Banking FEDERAL RESERVE SYSTEM BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM REIMBURSEMENT FOR PROVIDING FINANCIAL RECORDS; RECORDKEEPING REQUIREMENTS FOR CERTAIN FINANCIAL RECORDS (REGULATION S.... All records that are required to be retained by this subpart shall be retained for a period of five...

  20. 12 CFR 219.24 - Retention period.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... and Banking FEDERAL RESERVE SYSTEM BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM REIMBURSEMENT FOR PROVIDING FINANCIAL RECORDS; RECORDKEEPING REQUIREMENTS FOR CERTAIN FINANCIAL RECORDS (REGULATION S.... All records that are required to be retained by this subpart shall be retained for a period of five...

  1. 12 CFR 219.24 - Retention period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... and Banking FEDERAL RESERVE SYSTEM BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM REIMBURSEMENT FOR PROVIDING FINANCIAL RECORDS; RECORDKEEPING REQUIREMENTS FOR CERTAIN FINANCIAL RECORDS (REGULATION S.... All records that are required to be retained by this subpart shall be retained for a period of five...

  2. 7 CFR 955.13 - Fiscal period.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Fiscal period. 955.13 Section 955.13 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE VIDALIA ONIONS GROWN IN...

  3. 7 CFR 956.13 - Fiscal period.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Fiscal period. 956.13 Section 956.13 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE SWEET ONIONS GROWN IN THE WALLA...

  4. 7 CFR 955.113 - Fiscal period.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Fiscal period. 955.113 Section 955.113 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE VIDALIA ONIONS GROWN IN GEORGIA...

  5. 7 CFR 955.113 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 955.113 Section 955.113 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE VIDALIA ONIONS GROWN IN GEORGIA...

  6. 7 CFR 956.13 - Fiscal period.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Fiscal period. 956.13 Section 956.13 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE SWEET ONIONS GROWN IN THE WALLA...

  7. 7 CFR 955.13 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 955.13 Section 955.13 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE VIDALIA ONIONS GROWN IN...

  8. 7 CFR 955.13 - Fiscal period.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Fiscal period. 955.13 Section 955.13 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE VIDALIA ONIONS GROWN IN...

  9. 7 CFR 955.113 - Fiscal period.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Fiscal period. 955.113 Section 955.113 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE VIDALIA ONIONS GROWN IN GEORGIA...

  10. 7 CFR 956.13 - Fiscal period.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Fiscal period. 956.13 Section 956.13 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE SWEET ONIONS GROWN IN THE WALLA...

  11. 7 CFR 956.13 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 956.13 Section 956.13 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE SWEET ONIONS GROWN IN THE WALLA...

  12. 7 CFR 955.13 - Fiscal period.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Fiscal period. 955.13 Section 955.13 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE VIDALIA ONIONS GROWN IN...

  13. 7 CFR 955.113 - Fiscal period.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Fiscal period. 955.113 Section 955.113 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE VIDALIA ONIONS GROWN IN GEORGIA...

  14. 7 CFR 956.13 - Fiscal period.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Fiscal period. 956.13 Section 956.13 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE SWEET ONIONS GROWN IN THE WALLA...

  15. 7 CFR 955.13 - Fiscal period.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Fiscal period. 955.13 Section 955.13 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE VIDALIA ONIONS GROWN IN...

  16. 7 CFR 955.113 - Fiscal period.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Fiscal period. 955.113 Section 955.113 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE VIDALIA ONIONS GROWN IN GEORGIA...

  17. 7 CFR 922.7 - Fiscal period.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Fiscal period. 922.7 Section 922.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE APRICOTS GROWN IN DESIGNATED COUNTIES...

  18. 7 CFR 922.7 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 922.7 Section 922.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE APRICOTS GROWN IN DESIGNATED COUNTIES...

  19. 7 CFR 922.7 - Fiscal period.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Fiscal period. 922.7 Section 922.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE APRICOTS GROWN IN DESIGNATED COUNTIES...

  20. 7 CFR 922.7 - Fiscal period.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Fiscal period. 922.7 Section 922.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE APRICOTS GROWN IN DESIGNATED COUNTIES...

  1. 7 CFR 922.7 - Fiscal period.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Fiscal period. 922.7 Section 922.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE APRICOTS GROWN IN DESIGNATED COUNTIES...

  2. 46 CFR 535.604 - Waiting period.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 9 2010-10-01 2010-10-01 false Waiting period. 535.604 Section 535.604 Shipping FEDERAL MARITIME COMMISSION REGULATIONS AFFECTING OCEAN SHIPPING IN FOREIGN COMMERCE OCEAN COMMON CARRIER AND MARINE TERMINAL OPERATOR AGREEMENTS SUBJECT TO THE SHIPPING ACT OF 1984 Action on Agreements § 535.604...

  3. 7 CFR 948.10 - Fiscal period.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Fiscal period. 948.10 Section 948.10 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE IRISH POTATOES GROWN IN COLORADO...

  4. 7 CFR 948.10 - Fiscal period.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Fiscal period. 948.10 Section 948.10 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE IRISH POTATOES GROWN IN COLORADO...

  5. 7 CFR 948.10 - Fiscal period.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Fiscal period. 948.10 Section 948.10 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE IRISH POTATOES GROWN IN COLORADO...

  6. 7 CFR 948.10 - Fiscal period.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Fiscal period. 948.10 Section 948.10 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE IRISH POTATOES GROWN IN COLORADO...

  7. 7 CFR 1221.211 - Voting period.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Voting period. 1221.211 Section 1221.211 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH,...

  8. 7 CFR 1221.211 - Voting period.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Voting period. 1221.211 Section 1221.211 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH,...

  9. 7 CFR 1221.210 - Representative period.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Representative period. 1221.210 Section 1221.210 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH,...

  10. 7 CFR 1221.211 - Voting period.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Voting period. 1221.211 Section 1221.211 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH,...

  11. 7 CFR 1221.210 - Representative period.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Representative period. 1221.210 Section 1221.210 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH,...

  12. 7 CFR 1221.210 - Representative period.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Representative period. 1221.210 Section 1221.210 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH,...

  13. 7 CFR 1221.210 - Representative period.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Representative period. 1221.210 Section 1221.210 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH,...

  14. 7 CFR 1221.211 - Voting period.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Voting period. 1221.211 Section 1221.211 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH,...

  15. 7 CFR 981.73 - Periodic reports.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Periodic reports. 981.73 Section 981.73 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE ALMONDS GROWN IN CALIFORNIA Order...

  16. 7 CFR 981.73 - Periodic reports.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Periodic reports. 981.73 Section 981.73 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE ALMONDS GROWN IN CALIFORNIA Order...

  17. 7 CFR 981.73 - Periodic reports.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Periodic reports. 981.73 Section 981.73 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE ALMONDS GROWN IN CALIFORNIA Order...

  18. 7 CFR 981.73 - Periodic reports.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Periodic reports. 981.73 Section 981.73 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE ALMONDS GROWN IN CALIFORNIA Order...

  19. 7 CFR 981.73 - Periodic reports.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Periodic reports. 981.73 Section 981.73 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE ALMONDS GROWN IN CALIFORNIA Order...

  20. 7 CFR 945.12 - Fiscal period.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Fiscal period. 945.12 Section 945.12 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE IRISH POTATOES GROWN IN CERTAIN...

  1. 7 CFR 1220.612 - Representative period.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Representative period. 1220.612 Section 1220.612 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH,...

  2. 7 CFR 1220.612 - Representative period.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Representative period. 1220.612 Section 1220.612 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH,...

  3. 7 CFR 1220.612 - Representative period.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Representative period. 1220.612 Section 1220.612 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH,...

  4. 7 CFR 1220.612 - Representative period.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Representative period. 1220.612 Section 1220.612 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH,...

  5. 7 CFR 925.112 - Fiscal period.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Fiscal period. 925.112 Section 925.112 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA...

  6. 7 CFR 925.112 - Fiscal period.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Fiscal period. 925.112 Section 925.112 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA...

  7. 7 CFR 925.12 - Fiscal period.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Fiscal period. 925.12 Section 925.12 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA...

  8. 7 CFR 925.112 - Fiscal period.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Fiscal period. 925.112 Section 925.112 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA...

  9. 7 CFR 925.12 - Fiscal period.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Fiscal period. 925.12 Section 925.12 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA...

  10. 7 CFR 925.112 - Fiscal period.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Fiscal period. 925.112 Section 925.112 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA...

  11. 7 CFR 925.12 - Fiscal period.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Fiscal period. 925.12 Section 925.12 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA...

  12. 7 CFR 925.12 - Fiscal period.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Fiscal period. 925.12 Section 925.12 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA...

  13. 7 CFR 945.12 - Fiscal period.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Fiscal period. 945.12 Section 945.12 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE IRISH POTATOES GROWN IN...

  14. 7 CFR 945.12 - Fiscal period.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Fiscal period. 945.12 Section 945.12 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE IRISH POTATOES GROWN IN...

  15. 7 CFR 1150.107 - Fiscal period.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Fiscal period. 1150.107 Section 1150.107 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE DAIRY PROMOTION PROGRAM Dairy Promotion and Research...

  16. 7 CFR 1150.107 - Fiscal period.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Fiscal period. 1150.107 Section 1150.107 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE DAIRY PROMOTION PROGRAM Dairy Promotion and Research...

  17. 7 CFR 1150.107 - Fiscal period.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Fiscal period. 1150.107 Section 1150.107 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Milk), DEPARTMENT OF AGRICULTURE DAIRY PROMOTION PROGRAM Dairy Promotion and Research...

  18. 7 CFR 905.11 - Fiscal period.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Fiscal period. 905.11 Section 905.11 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE ORANGES, GRAPEFRUIT, TANGERINES, AND...

  19. 7 CFR 905.11 - Fiscal period.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Fiscal period. 905.11 Section 905.11 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE ORANGES, GRAPEFRUIT, TANGERINES, AND...

  20. 7 CFR 905.11 - Fiscal period.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Fiscal period. 905.11 Section 905.11 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE ORANGES, GRAPEFRUIT, TANGERINES, AND...

  1. 7 CFR 905.11 - Fiscal period.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Fiscal period. 905.11 Section 905.11 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE ORANGES, GRAPEFRUIT, TANGERINES, AND...

  2. 7 CFR 929.106 - Fiscal period.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Fiscal period. 929.106 Section 929.106 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE CRANBERRIES GROWN IN STATES OF...

  3. 7 CFR 929.106 - Fiscal period.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Fiscal period. 929.106 Section 929.106 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE CRANBERRIES GROWN IN STATES OF...

  4. 7 CFR 929.6 - Fiscal period.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Fiscal period. 929.6 Section 929.6 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE CRANBERRIES GROWN IN STATES OF...

  5. 7 CFR 929.6 - Fiscal period.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Fiscal period. 929.6 Section 929.6 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE CRANBERRIES GROWN IN STATES OF...

  6. 7 CFR 929.6 - Fiscal period.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Fiscal period. 929.6 Section 929.6 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE CRANBERRIES GROWN IN STATES OF...

  7. 7 CFR 929.106 - Fiscal period.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Fiscal period. 929.106 Section 929.106 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE CRANBERRIES GROWN IN STATES OF...

  8. 7 CFR 929.6 - Fiscal period.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Fiscal period. 929.6 Section 929.6 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE CRANBERRIES GROWN IN STATES OF...

  9. 7 CFR 929.106 - Fiscal period.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Fiscal period. 929.106 Section 929.106 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE CRANBERRIES GROWN IN STATES OF...

  10. 17 CFR 289.2 - Periodic reports.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Periodic reports. 289.2 Section 289.2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) Schedule A to Part 285 GENERAL RULES AND REGULATIONS PURSUANT TO SECTION 13(a) OF THE INTERNATIONAL...

  11. 7 CFR 925.12 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 925.12 Section 925.12 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA OF...

  12. 7 CFR 925.112 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 925.112 Section 925.112 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA OF...

  13. 49 CFR 232.611 - Periodic maintenance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Periodic maintenance. 232.611 Section 232.611 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... maintenance. (a) In addition to the maintenance requirements contained in § 232.303(b) through (d), a freight...

  14. 50 CFR 424.21 - Periodic review.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A LISTING ENDANGERED AND THREATENED SPECIES AND DESIGNATING CRITICAL HABITAT Revision of the Lists § 424.21 Periodic review. At least once every 5 years, the Secretary shall conduct a review of each listed species to determine whether...

  15. 50 CFR 424.21 - Periodic review.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A LISTING ENDANGERED AND THREATENED SPECIES AND DESIGNATING CRITICAL HABITAT Revision of the Lists § 424.21 Periodic review. At least once every 5 years, the Secretary shall conduct a review of each listed species to determine whether...

  16. 50 CFR 424.21 - Periodic review.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A LISTING ENDANGERED AND THREATENED SPECIES AND DESIGNATING CRITICAL HABITAT § 424.21 Periodic review. At least once every 5 years, the Secretary shall conduct a review of each listed species to determine whether it should be delisted...

  17. 7 CFR 930.7 - Fiscal period.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Fiscal period. 930.7 Section 930.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE TART CHERRIES GROWN IN THE STATES OF...

  18. 7 CFR 923.7 - Fiscal period.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Fiscal period. 923.7 Section 923.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE SWEET CHERRIES GROWN IN DESIGNATED...

  19. 7 CFR 930.7 - Fiscal period.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Fiscal period. 930.7 Section 930.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE TART CHERRIES GROWN IN THE STATES OF...

  20. 7 CFR 923.7 - Fiscal period.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Fiscal period. 923.7 Section 923.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE SWEET CHERRIES GROWN IN DESIGNATED...

  1. 7 CFR 930.7 - Fiscal period.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Fiscal period. 930.7 Section 930.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE TART CHERRIES GROWN IN THE STATES OF...

  2. 7 CFR 930.7 - Fiscal period.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Fiscal period. 930.7 Section 930.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE TART CHERRIES GROWN IN THE STATES OF...

  3. 7 CFR 923.7 - Fiscal period.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Fiscal period. 923.7 Section 923.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE SWEET CHERRIES GROWN IN DESIGNATED...

  4. 7 CFR 923.7 - Fiscal period.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Fiscal period. 923.7 Section 923.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE SWEET CHERRIES GROWN IN DESIGNATED...

  5. 7 CFR 930.7 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 930.7 Section 930.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE TART CHERRIES GROWN IN THE STATES OF...

  6. 7 CFR 923.7 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 923.7 Section 923.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE SWEET CHERRIES GROWN IN DESIGNATED...

  7. 7 CFR 966.16 - Fiscal period.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Fiscal period. 966.16 Section 966.16 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE TOMATOES GROWN IN FLORIDA Order...

  8. 7 CFR 966.16 - Fiscal period.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Fiscal period. 966.16 Section 966.16 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE TOMATOES GROWN IN FLORIDA Order...

  9. 7 CFR 966.16 - Fiscal period.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Fiscal period. 966.16 Section 966.16 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE TOMATOES GROWN IN FLORIDA Order...

  10. 7 CFR 966.16 - Fiscal period.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Fiscal period. 966.16 Section 966.16 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE TOMATOES GROWN IN FLORIDA Order...

  11. 7 CFR 920.7 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Fiscal period. 920.7 Section 920.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE KIWIFRUIT GROWN IN...

  12. 7 CFR 920.7 - Fiscal period.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Fiscal period. 920.7 Section 920.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE KIWIFRUIT GROWN IN...

  13. 7 CFR 920.7 - Fiscal period.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Fiscal period. 920.7 Section 920.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE KIWIFRUIT GROWN IN...

  14. 7 CFR 920.7 - Fiscal period.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Fiscal period. 920.7 Section 920.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE KIWIFRUIT GROWN IN...

  15. 7 CFR 920.7 - Fiscal period.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Fiscal period. 920.7 Section 920.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE KIWIFRUIT GROWN IN...

  16. Hyperthyroid hypokalemic periodic paralysis

    PubMed Central

    Neki, N.S.

    2016-01-01

    Hyperthyroid periodic paralysis (HPP) is a rare life threatening complication of hyperthyroidism commonly occurring in young Asian males but sporadically found in other races. It is characterised by hypokalemia and acute onset paraparesis with prevalence of one in one hundred thousand (1 in 100000). The symptoms resolve promptly with potassium supplementation. Nonselective beta blockers like propranol can also be used to ameliorate and prevent subsequent paralytic attack. We report a case of 22 year old male presenting with hyperthyroid periodic paralysis (HPP) having very low serum potassium level. PMID:27648066

  17. "Ictal" lateralized periodic discharges.

    PubMed

    Sen-Gupta, Indranil; Schuele, Stephan U; Macken, Micheal P; Kwasny, Mary J; Gerard, Elizabeth E

    2014-07-01

    Whether lateralized periodic discharges (LPDs) represent ictal or interictal phenomena, and even the circumstances in which they may represent one or the other, remains highly controversial. Lateralized periodic discharges are, however, widely accepted as being ictal when they are time-locked to clinically apparent symptoms. We sought to investigate the characteristics of "ictal" lateralized periodic discharges (ILPDs) defined by time-locked clinical symptoms in order to explore the utility of using this definition to dichotomize LPDs into "ictal" and "nonictal" categories. Our archive of all continuous EEG (cEEG) reports of adult inpatients undergoing prolonged EEG monitoring for nonelective indications between 2007 and 2011 was searched to identify all reports describing LPDs. Lateralized periodic discharges were considered ILPDs when they were reported as being consistently time-locked to clinical symptoms; LPDs lacking a clear time-locked correlate were considered to be "nonictal" lateralized periodic discharges (NILPDs). Patient charts and available neuroimaging studies were also reviewed. Neurophysiologic localization of LPDs, imaging findings, presence of seizures, discharge outcomes, and other demographic factors were compared between patients with ILPDs and those with NILPDs. p-Values were adjusted for false discovery rate (FDR). One thousand four hundred fifty-two patients underwent cEEG monitoring at our institution between 2007 and 2011. Lateralized periodic discharges were reported in 90 patients, 10 of whom met criteria for ILPDs. Nine of the patients with ILPDs demonstrated motor symptoms, and the remaining patient experienced stereotyped sensory symptoms. Ictal lateralized periodic discharges had significantly increased odds for involving central head regions (odds ratio [OR]=11; 95% confidence interval [CI]=2.16-62.6; p=0.018, FDR adjusted), with a trend towards higher proportion of lesions involving the primary sensorimotor cortex (p=0.09, FDR

  18. 12 CFR 707.6 - Periodic statement disclosures.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Periodic statement disclosures. 707.6 Section 707.6 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS TRUTH IN SAVINGS § 707.6 Periodic statement disclosures. (a) Rule when statement and crediting periods vary...

  19. 7 CFR 1.603 - How are time periods computed?

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 1 2013-01-01 2013-01-01 false How are time periods computed? 1.603 Section 1.603 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE REGULATIONS Conditions in FERC Hydropower Licenses General Provisions § 1.603 How are time periods computed? (a) General. Time periods are...

  20. 7 CFR 1.603 - How are time periods computed?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 1 2012-01-01 2012-01-01 false How are time periods computed? 1.603 Section 1.603 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE REGULATIONS Conditions in FERC Hydropower Licenses General Provisions § 1.603 How are time periods computed? (a) General. Time periods are...