Modeling the Transport and Radiative Forcing of Taklimakan Dust over the Tibetan Plateau: A case study in the summer of 2006

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

Chen, Siyu; Huang, J.; Zhao, Chun

2013-01-30

The Weather Research and Forecasting model with chemistry (WRF-Chem) is used to investigate an intense dust storm event during 26 to 30 July 2006 that originated over the Taklimakan Desert (TD) and transported to the northern slope of Tibetan Plateau (TP). The dust storm is initiated by the approach of a strong cold frontal system over the TD. In summer, the meridional transport of TD dust to the TP is favored by the thermal effect of the TP and the weakening of the East Asian westerly winds. During this dust storm, the transport of TD dust over the TP ismore » further enhanced by the passage of the cold front. As a result, TD dust breaks through the planetary boundary layer and extends to the upper troposphere over the northern TP. TD dust flux arrived at the TP with a value of 6.6 Gg/day in this 5 day event but decays quickly during the southward migration over the TP due to dry deposition. The simulations show that TD dust cools the atmosphere near the surface and heats the atmosphere above with a maximum heating rate of 0.11 K day-1 at ~7 km over the TP. The event-averaged net radiative forcings of TD dust over the TP are -3.97, 1.61, and -5.58 Wm-2 at the top of the atmosphere (TOA), in the atmosphere, and at the surface, respectively. The promising performance of WRF-Chem in simulating dust and its radiative forcing provides confidence for use in further investigation of climatic impact of TD dust over the TP.« less

Statistical downscaling forecast of Chinese winter temperature based on the autumn SST anomalies

NASA Astrophysics Data System (ADS)

Lu, J.

2017-12-01

This study investigates the impacts of the autumn sea surface temperature anomalies (SSTA) on interannual variations of Chinese winter temperature, and discusses the potential predictability of December-January-February (DJF) 2-m air temperature anomalies (TSA) over China based on the intimate linkage between the DJF TSA and autumn SSTA. According to the Empirical Orthogonal Function (EOF) analysis, three leading EOF modes jointly account for 80% of the total TSA variances and are characterized by a homogeneous spatial pattern, a north-south seesaw and a cross structure. The first three EOFs exhibit a stable feature revealed by cross-validation, suggesting the potential predictability of the DJF TSA. The EOF1 mode is influenced by changes in the intensities of the Siberian High (SH), East Asian winter monsoon (EAWM) and East Asian Trough related to an Eurasian pattern teleconnection, which can be tracked back to September-October-November (SON) SSTA associated with two SSTA tripole patterns in the North Pacific and North Atlantic, a dipole mode in the Indian Ocean and an ENSO-like mode in the equatorial and subtropical Pacific. However, the Arctic Oscillation plays an important role in the second mode. The teleconnection connecting the atmospheric circulation anomalies in two hemispheres indicates that the configuration of global SON SSTA induces the two annular modes and causes a TSA oscillation between the northern and southern parts of China. The third mode is related to the westward shift of the SH and western pathway EAWM, which are attributed to two dipole modes in the North Pacific and South Pacific, Atlantic Multidecadal Oscillation and Indian Ocean Basin Mode. Therefore a physically-based statistical model is established based on autumn SSTA indices. Cross-validation suggests that this statistical downscaling forecast model shows a good performance in predicting the DJF TSA.

The influence of sea surface temperature anomalies on low-frequency variability of the North Atlantic Oscillation

NASA Astrophysics Data System (ADS)

Manganello, Julia V.

2008-05-01

The influence of sea surface temperature anomalies (SSTA) on multi-year persistence of the North Atlantic Oscillation (NAO) during the second half of the twentieth century is investigated using the Center for Ocean-Land-Atmosphere Studies (COLA) Atmospheric GCM (AGCM) with an emphasis on isolating the geographic location of the SSTA that produce this influence. The present study focuses on calculating the atmospheric response to the SSTA averaged over 1988 1995 (1961 1968) corresponding to the observed period of strong persistence of the positive (negative) phase of the decadal NAO. The model response to the global 1988 1995 average SSTA shows a statistically significant large-scale pattern characteristic of the positive phase of the NAO. Forcing with the global 1961 1968 average SSTA generates a NAO of the opposite polarity compared to observations. However, all large-scale features both in the model and observations during this period are weaker in magnitude and less significant compared to 1988 1995. Additional idealized experiments show that over the northern center of the NAO the non-linear component of the forced response appears to be quite important and acts to enhance the positive NAO signal. On the other hand, over the southern center where the model response is the strongest, it is also essentially linear. The 1988 1995 average SSTA restricted to the western tropical Pacific region produce a positive NAO remarkably similar in structure but stronger in magnitude than the model response to the global and tropical Indo-Pacific 1988 1995 forcing. A 200-hPa geopotential height response in these experiments shows a positive anomaly over the southern center of the NAO embedded in the Rossby wave trains propagating from the western tropical Pacific. Indian Ocean SSTA lead to much weaker positive NAO primarily through the effect on its northern center. SST forcing confined to the North Atlantic north of equator does not produce a response statistically different from the control simulation, suggesting that it is not strong enough to significantly affect the phase of the decadal NAO. Inclusion of the South Atlantic north of 45° south does not change this result.

Lake seasonality across the Tibetan Plateau and their varying relationship with regional mass changes and local hydrology

NASA Astrophysics Data System (ADS)

Lei, Yanbin; Yao, Tandong; Yang, Kun; Sheng, Yongwei; Kleinherenbrink, Marcel; Yi, Shuang; Bird, Broxton W.; Zhang, Xiaowen; Zhu, La; Zhang, Guoqing

2017-01-01

The recent growth and deepening of inland lakes in the Tibetan Plateau (TP) may be a salient indicator of the consequences of climate change. The seasonal dynamics of these lakes is poorly understood despite this being potentially crucial for disentangling contributions from glacier melt and precipitation, which are all sensitive to climate, to lake water budget. Using in situ observations, satellite altimetry and gravimetry data, we identified two patterns of lake level seasonality. In the central, northern, and northeastern TP, lake levels are characterized by considerable increases during warm seasons and decreases during cold seasons, which is consistent with regional mass changes related to monsoon precipitation and evaporation. In the northwestern TP, however, lake levels exhibit dramatic increases during both warm and cold seasons, which deviate from regional mass changes. This appears to be more connected with high spring snowfall and large summer glacier melt. The variable lake level response to different drivers indicates heterogeneous sensitivity to climate change between the northwestern TP and other regions.

Cold, dry air is associated with influenza and pneumonia mortality in Auckland, New Zealand.

PubMed

Davis, Robert E; Dougherty, Erin; McArthur, Colin; Huang, Qiu Sue; Baker, Michael G

2016-07-01

The relationship between weather and influenza and pneumonia mortality was examined retrospectively using daily data from 1980 to 2009 in Auckland, New Zealand, a humid, subtropical location. Mortality events, defined when mortality exceeded 0·95 standard deviation above the mean, followed periods of anomalously cold air (ta.m. = -4·1, P < 0·01; tp.m. = -4·2, P < 0·01) and/or anomalously dry air (ta.m. = -4·1, P < 0·01; tp.m. = -3·8, P < 0·01) by up to 19 days. These results suggest that respiratory infection is enhanced during unusually cold conditions and during conditions with unusually low humidity, even in a subtropical location where humidity is typically high. © 2015 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Differences among total and in vitro digestible phosphorus content of meat and milk products.

PubMed

Karp, Heini; Ekholm, Päivi; Kemi, Virpi; Hirvonen, Tero; Lamberg-Allardt, Christel

2012-05-01

Meat and milk products are important sources of dietary phosphorus (P) and protein. The use of P additives is common both in processed cheese and meat products. Measurement of in vitro digestible phosphorus (DP) content of foods may reflect absorbability of P. The objective of this study was to measure both total phosphorus (TP) and DP contents of selected meat and milk products and to compare amounts of TP and DP and the proportion of DP to TP among different foods. TP and DP contents of 21 meat and milk products were measured by inductively coupled plasma optical emission spectrometry (ICP-OES). In DP analysis, samples were digested enzymatically, in principle, in the same way as in the alimentary canal before the analyses. The most popular national brands of meat and milk products were chosen for analysis. The highest TP and DP contents were found in processed and hard cheeses; the lowest, in milk and cottage cheese. TP and DP contents in sausages and cold cuts were lower than those in cheeses. Chicken, pork, beef, and rainbow trout contained similar amounts of TP, but slightly more variation was found in their DP contents. Foods containing P additives have a high content of DP. Our study confirms that cottage cheese and unenhanced meats are better choices than processed or hard cheeses, sausages, and cold cuts for chronic kidney disease patients, based on their lower P-to-protein ratios and sodium contents. The results support previous findings of better P absorbability in foods of animal origin than in, for example, legumes. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

The interdecadal changes of south pacific sea surface temperature in the mid-1990s and their connections with ENSO

NASA Astrophysics Data System (ADS)

Li, Gang; Li, Chongyin; Tan, Yanke; Bai, Tao

2014-01-01

The characteristic changes of South Pacific sea surface temperature anomalies (SSTAs) for the period January 1979 to December 2011, during which the 1990s Pacific pan-decadal variability (PDV) interdecadal regime shifts occurred, were examined. Empirical Orthogonal Function (EOF) analysis was applied to the monthly mean SSTA for two sub-periods: January 1979 to December 1994 (P1) and January 1996 to December 2011 (P2). Both the spatial and temporal features of the leading EOF mode for P1 and P2 showed a remarkable difference. The spatial structure of the leading EOF changed from a tripolar pattern for P1 (EOF-P1) to a dipole-like pattern for P2 (EOF-P2). Besides, EOF-P1 (EOF-P2) had significant spectral peaks at 4.6 yr (2.7 yr). EOF-P2 not only had a closer association with El Niño-Southern Oscillation (ENSO), but also showed a faster response to ENSO than EOF-P1 based on their lead-lag relationships with ENSO. During the development of ENSO, the South Pacific SSTA associated with ENSO for both P1 and P2 showed a significant eastward propagation. However, after the peak of ENSO, EOF-P1 showed a stronger persistence than EOF-P2, which still showed eastward propagation. The variability of the SSTA associated with the whole process of ENSO evolution during P1 and the SSTA associated with the development of ENSO during P2 support the existence of ocean-to-atmosphere forcing, but the SSTA associated with the decay of ENSO shows the phenomenon of atmosphere-to-ocean forcing.

Relationships between the extratropical ENSO precursor and leading modes of atmospheric variability in the Southern Hemisphere

NASA Astrophysics Data System (ADS)

Qin, Jianhuang; Ding, Ruiqiang; Wu, Zhiwei; Li, Jianping; Zhao, Sen

2017-03-01

Previous studies suggest that the atmospheric precursor of El Niño-Southern Oscillation (ENSO) in the extratropical Southern Hemisphere (SH) might trigger a quadrapole sea surface temperature anomaly (SSTA) in the South Pacific and subsequently influence the following ENSO. Such a quadrapole SSTA is referred to as the South Pacific quadrapole (SPQ). The present study investigated the relationships between the atmospheric precursor signal of ENSO and leading modes of atmospheric variability in the extratropical SH [including the SH annular mode (SAM), the first Pacific-South America (PSA1) mode, and the second Pacific-South America (PSA2) mode]. The results showed that the atmospheric precursor signal in the extratropical SH basically exhibits a barotropic wavenumber-3 structure over the South Pacific and is significantly correlated with the SAM and the PSA2 mode during austral summer. Nevertheless, only the PSA2 mode was found to be a precursor for the following ENSO. It leads the SPQ-like SSTA by around one month, while the SAM and the PSA1 mode do not show any obvious linkage with either ENSO or the SPQ. This suggests that the PSA2 mode may provide a bridge between the preceding circulation anomalies over the extratropical SH and the following ENSO through the SPQ-like SSTA.

Potential regulation on the climatic effect of Tibetan Plateau heating by tropical air-sea coupling in regional models

NASA Astrophysics Data System (ADS)

Wang, Ziqian; Duan, Anmin; Yang, Song

2018-05-01

Based on the conventional weather research and forecasting (WRF) model and the air-sea coupled mode WRF-OMLM, we investigate the potential regulation on the climatic effect of Tibetan Plateau (TP) heating by the air-sea coupling over the tropical Indian Ocean and western Pacific. Results indicate that the TP heating significantly enhances the southwesterly monsoon circulation over the northern Indian Ocean and the South Asia subcontinent. The intensified southwesterly wind cools the sea surface mainly through the wind-evaporation-SST (sea surface temperature) feedback. Cold SST anomaly then weakens monsoon convective activity, especially that over the Bay of Bengal, and less water vapor is thus transported into the TP along its southern slope from the tropical oceans. As a result, summer precipitation decreases over the TP, which further weakens the TP local heat source. Finally, the changed TP heating continues to influence the summer monsoon precipitation and atmospheric circulation. To a certain extent, the air-sea coupling over the adjacent oceans may weaken the effect of TP heating on the mean climate in summer. It is also implied that considerations of air-sea interaction are necessary in future simulation studies of the TP heating effect.

Antioxidant Bioactive Compounds Changes in Fruit of Quince Genotypes Over Cold Storage.

PubMed

Moradi, Samira; Koushesh Saba, Mahmoud; Mozafari, Ali Akbar; Abdollahi, Hamid

2016-07-01

Quince fruit has many benefits to human health and is excellent source of bioactive compounds. The fruit of 15 quince genotypes stored at 2 °C for 5 mo to study fruit quality changes during cold storage. Fruit were sampled monthly and stored at 20 °C for 24 h. Fruit ascorbic acid (AA), total phenol (TP), and total flavonoid (TF) concentrations, total antioxidant activity (TAA), flesh browning (FB) incidence, polyphenol oxidase (PPO), peroxidase (POX), and superoxide dismutase (SOD) activities were measured during storage. A high variation in bioactive compounds was observed across genotypes. The range of 26.8 to 44.4 mg/100 g FW for AA, 86.7% to 98.2% for TAA, 157.7 to 380.7 mg GAE 100(-1) g FW for TP, and 5.3 to 10.7 mg/100 g FW for TF were observed across genotypes at harvest time. The overall AA, TAA, TP, TF, and SOD decreased while PPO and POX increased during storage. FB was first observed after 4 mo and increased thereafter while the FB index was different across genotypes. Higher bioactive content may prevent or reduce FB index so that a negative correlation was found between FB and AA, TAA, TP, TF, and SOD. © 2016 Institute of Food Technologists®

Three centuries of winter temperature change on the southeastern Tibetan Plateau and its relationship with the Atlantic Multidecadal Oscillation

NASA Astrophysics Data System (ADS)

Shi, Shiyuan; Li, Jinbao; Shi, Jiangfeng; Zhao, Yesi; Huang, Gang

2017-08-01

Long-term, high-resolution proxy records containing cold season temperature signals are scarce on the southeastern Tibetan Plateau (TP), limiting our understanding of regional climate and the potential driving forces. In this study, we present a nearly three centuries long reconstruction of winter (December-February) mean temperature for the central Hengduan Mountains, southeastern TP. The reconstruction is derived from a composite tree-ring width chronology of Pinus yunnanensis Franch from two high elevation sites (>3000 m above sea level). Our reconstruction passes all standard calibration-verification schemes and explains nearly 73 % of the variance of the original instrumental data. However, we were constrained to calibrate our full period (1718-2013) reconstruction of December-February mean temperature on the calibration period from 1959 to 1992 only, due to a decrease in temperature sensitivity of tree-ring index exhibited after 1992. Spatial correlation analysis shows that our reconstruction represents large-scale temperature variations in southwest China and the eastern TP. Our reconstructed December-February mean temperature shows a close association with the Atlantic Multidecadal Oscillation (AMO) over the past three centuries, with warm (cold) periods coinciding with the positive (negative) phases of the AMO. This persistent relationship suggests that the AMO may have been a key driver of multidecadal winter temperature variations on the southeastern TP.

[Effect of Acaí (Euterpe oleracea) on biological expression characteristics of deficiency-heat and deficiency-cold rats].

PubMed

Wang, Lin-Yuan; Zhang, Jian-Jun; Wang, Chun; Zhu, Ying-Li; Wang, Zi-Chen; He, Cheng; Qu, Yan; Wang, Sha

2016-10-01

To study the effects of Acaí on biological expression characteristics in rats with deficiency-heat and deficiency-cold syndromes, SD rats were divided into blank group, deficiency-heat model group, deficiency-heat+Phellodendri Chinensis Cortex group, deficiency-heat+Acaí high dose and low dose groups, deficiency-cold model group, deficiency-cold+Cinnamomi Cortex group, deficiency-cold+Acaí high dose and low dose groups. The rats were treated with intramuscular injection of hydrocortisone (20 mg•kg⁻¹) or dexamethasone sodium phosphate (0.35 mg•kg⁻¹) for 21 days to set up deficiency-heat model and deficiency-cold models. The levels of cAMP, cGMP, T3, T4 and rT3 were detected by radioimmunoassay. The levels of TP, UA, TC, TG and ALB were detected by colorimetry. The level of cAMP, cAMP/cGMP in serum were reduced in Acaí high dose group (P<0.05, P<0.001). The levels of T3, T4 and rT3 were significantly reduced in the Acaí high dose group (P<0.01, P<0.001, P<0.05). The levels of TP, UA, TC, TG and ALB were significantly reduced in the Acaí high dose group (P<0.001, P<0.05, P<0.05, P<0.05, P<0.01). However, Acaí had no obvious effects on deficiency-cold models. Acaí showed the same effect with Phellodendri Chinensis Cortex in adjusting the levels of deficiency-heat rats; but unlike Cinnamomi Cortex, Acaí showed no obvious effects in adjusting the levels of deficiency-cold rats. Copyright© by the Chinese Pharmaceutical Association.

Forecasting experiments of a dynamical-statistical model of the sea surface temperature anomaly field based on the improved self-memorization principle

NASA Astrophysics Data System (ADS)

Hong, Mei; Chen, Xi; Zhang, Ren; Wang, Dong; Shen, Shuanghe; Singh, Vijay P.

2018-04-01

With the objective of tackling the problem of inaccurate long-term El Niño-Southern Oscillation (ENSO) forecasts, this paper develops a new dynamical-statistical forecast model of the sea surface temperature anomaly (SSTA) field. To avoid single initial prediction values, a self-memorization principle is introduced to improve the dynamical reconstruction model, thus making the model more appropriate for describing such chaotic systems as ENSO events. The improved dynamical-statistical model of the SSTA field is used to predict SSTA in the equatorial eastern Pacific and during El Niño and La Niña events. The long-term step-by-step forecast results and cross-validated retroactive hindcast results of time series T1 and T2 are found to be satisfactory, with a Pearson correlation coefficient of approximately 0.80 and a mean absolute percentage error (MAPE) of less than 15 %. The corresponding forecast SSTA field is accurate in that not only is the forecast shape similar to the actual field but also the contour lines are essentially the same. This model can also be used to forecast the ENSO index. The temporal correlation coefficient is 0.8062, and the MAPE value of 19.55 % is small. The difference between forecast results in spring and those in autumn is not high, indicating that the improved model can overcome the spring predictability barrier to some extent. Compared with six mature models published previously, the present model has an advantage in prediction precision and length, and is a novel exploration of the ENSO forecast method.

Global weather and local butterflies: variable responses to a large-scale climate pattern along an elevational gradient.

PubMed

Pardikes, Nicholas A; Shapiro, Arthur M; Dyer, Lee A; Forister, Matthew L

2015-11-01

Understanding the spatial and temporal scales at which environmental variation affects populations of plants and animals is an important goal for modern population biology, especially in the context of shifting climatic conditions. The El Niño Southern Oscillation (ENSO) generates climatic extremes of interannual variation, and has been shown to have significant effects on the diversity and abundance of a variety of terrestrial taxa. However, studies that have investigated the influence of such large-scale climate phenomena have often been limited in spatial and taxonomic scope. We used 23 years (1988-2010) of a long-term butterfly monitoring data set to explore associations between variation in population abundance of 28 butterfly species and variation in ENSO-derived sea surface temperature anomalies (SSTA) across 10 sites that encompass an elevational range of 2750 m in the Sierra Nevada mountain range of California. Our analysis detected a positive, regional effect of increased SSTA on butterfly abundance (wetter and warmer years predict more butterfly observations), yet the influence of SSTA on butterfly abundances varied along the elevational gradient, and also differed greatly among the 28 species. Migratory species had the strongest relationships with ENSO-derived SSTA, suggesting that large-scale climate indices are particularly valuable for understanding biotic-abiotic relationships of the most mobile species. In general, however, the ecological effects of large-scale climatic factors are context dependent between sites and species. Our results illustrate the power of long-term data sets for revealing pervasive yet subtle climatic effects, but also caution against expectations derived from exemplar species or single locations in the study of biotic-abiotic interactions.

Severe Drought Event in Indonesia Following 2015/16 El Niño/positive Indian Dipole Events

NASA Astrophysics Data System (ADS)

Lestari, D. O.; Sutriyono, E.; Sabaruddin; Iskandar, I.

2018-04-01

During boreal fall and winter 2015/16, Indonesia experienced catastrophic drought event causing many environmental problems. This study explored dynamical evolution of drought event in Indonesia associated with those two climate modes. Based on the Niño3.4 index, the evolution of the El Niño has started in April 2015, reached its peak in January 2016 and terminated in April 2016. Meanwhile, the Dipole Mode Index (DMI) revealed that the evolution of positive Indian Ocean Dipole has started in August, reached its peak in September and terminated in November 2015. It is shown that during those two events, Indonesia experienced severe drought in which the precipitation was extremely decreased. During the peak drought condition co-occurring with the dry season, the anomalous of precipitation reached ‑450 mm/month in September 2015. The peak of the drought was associated with the El Niño and positive Indian Ocean Dipole sea surface temperature anomaly (SSTA) patterns, in which negative SSTA covered the eastern tropical Indian Ocean and the western Pacific Ocean including Indonesia seas. Meanwhile, positive SSTA observed in the western tropical Indian Ocean and Eastern Pacific Ocean.

Predicting Kenya Short Rains Using the Indian Ocean SST

NASA Astrophysics Data System (ADS)

Peng, X.; Albertson, J. D.; Steinschneider, S.

2017-12-01

The rainfall over the Eastern Africa is charaterized by the typical bimodal monsoon system. Literatures have shown that the monsoon system is closely connected with the large-scale atmospheric motion which is believed to be driven by sea surface temperature anomalies (SSTA). Therefore, we may make use of the predictability of SSTA in estimating future Easter Africa monsoon. In this study, we tried predict the Kenya short rains (Oct, Nov and Dec rainfall) based on the Indian Ocean SSTA. The Least Absolute Shrinkage and Selection Operator (LASSO) regression is used to avoid over-fitting issues. Models for different lead times are trained using a 28-year training set (2006-1979) and are tested using a 10-year test set (2007-2016). Satisfying prediciton skills are achieved at relatively long lead times (i.e., 8 and 10 months) in terms of correlation coefficient and sign accuracy. Unlike some of the previous work, the prediction models are obtained from a data-driven method. Limited predictors are selected for each model and can be used in understanding the underlying physical connection. Still, further investigation is needed since the sampling variability issue cannot be excluded due to the limited sample size.

Estimation of Global Subsurface Thermal Structure from Satellite Remote Sensing Observations Based on Machine Learning

NASA Astrophysics Data System (ADS)

Su, H.; Yan, X. H.

2017-12-01

Subsurface thermal structure of the global ocean is a key factor that reflects the impact of the global climate variability and change. Accurately determining and describing the global subsurface and deeper ocean thermal structure from satellite measurements is becoming even more important for understanding the ocean interior anomaly and dynamic processes during recent global warming and hiatus. It is essential but challenging to determine the extent to which such surface remote sensing observations can be used to develop information about the global ocean interior. This study proposed a Support Vector Regression (SVR) method to estimate Subsurface Temperature Anomaly (STA) in the global ocean. The SVR model can well estimate the global STA upper 1000 m through a suite of satellite remote sensing observations of sea surface parameters (including Sea Surface Height Anomaly (SSHA), Sea Surface Temperature Anomaly (SSTA), Sea Surface Salinity Anomaly (SSSA) and Sea Surface Wind Anomaly (SSWA)) with in situ Argo data for training and testing at different depth levels. Here, we employed the MSE and R2 to assess SVR performance on the STA estimation. The results from the SVR model were validated for the accuracy and reliability using the worldwide Argo STA data. The average MSE and R2 of the 15 levels are 0.0090 / 0.0086 / 0.0087 and 0.443 / 0.457 / 0.485 for 2-attributes (SSHA, SSTA) / 3-attributes (SSHA, SSTA, SSSA) / 4-attributes (SSHA, SSTA, SSSA, SSWA) SVR, respectively. The estimation accuracy was improved by including SSSA and SSWA for SVR input (MSE decreased by 0.4% / 0.3% and R2 increased by 1.4% / 4.2% on average). While, the estimation accuracy gradually decreased with the increase of the depth from 500 m. The results showed that SSSA and SSWA, in addition to SSTA and SSHA, are useful parameters that can help estimate the subsurface thermal structure, as well as improve the STA estimation accuracy. In future, we can figure out more potential and useful sea surface parameters from satellite remote sensing as input attributes so as to further improve the STA sensing accuracy from machine learning. This study can provide a helpful technique for studying thermal variability in the ocean interior which has played an important role in recent global warming and hiatus from satellite observations over global scale.

Short circuit of water vapor and polluted air to the global stratosphere by convective transport over the Tibetan Plateau

PubMed Central

Fu, Rong; Hu, Yuanlong; Wright, Jonathon S.; Jiang, Jonathan H.; Dickinson, Robert E.; Chen, Mingxuan; Filipiak, Mark; Read, William G.; Waters, Joe W.; Wu, Dong L.

2006-01-01

During boreal summer, much of the water vapor and CO entering the global tropical stratosphere is transported over the Asian monsoon/Tibetan Plateau (TP) region. Studies have suggested that most of this transport is carried out either by tropical convection over the South Asian monsoon region or by extratropical convection over southern China. By using measurements from the newly available National Aeronautics and Space Administration Aura Microwave Limb Sounder, along with observations from the Aqua and Tropical Rainfall-Measuring Mission satellites, we establish that the TP provides the main pathway for cross-tropopause transport in this region. Tropospheric moist convection driven by elevated surface heating over the TP is deeper and detrains more water vapor, CO, and ice at the tropopause than over the monsoon area. Warmer tropopause temperatures and slower-falling, smaller cirrus cloud particles in less saturated ambient air at the tropopause also allow more water vapor to travel into the lower stratosphere over the TP, effectively short-circuiting the slower ascent of water vapor across the cold tropical tropopause over the monsoon area. Air that is high in water vapor and CO over the Asian monsoon/TP region enters the lower stratosphere primarily over the TP, and it is then transported toward the Asian monsoon area and disperses into the large-scale upward motion of the global stratospheric circulation. Thus, hydration of the global stratosphere could be especially sensitive to changes of convection over the TP. PMID:16585523

Cold ischemia with selective anterograde in situ pulmonary perfusion preserves gas exchange and mitochondrial homeostasis and curbs inflammation in an experimental model of donation after cardiac death.

PubMed

Pottecher, Julien; Santelmo, Nicola; Noll, Eric; Charles, Anne-Laure; Benahmed, Malika; Canuet, Matthieu; Frossard, Nelly; Namer, Izzie J; Geny, Bernard; Massard, Gilbert; Diemunsch, Pierre

2013-10-01

The aim of this study was to assess the functional preservation of the lung graft with anterograde lung perfusion in a model of donation after cardiac death. Thirty minutes after cardiac arrest, in situ anterograde selective pulmonary cold perfusion was started in six swine. The alveolo-capillary membrane was challenged at 3, 6, and 8 h with measurements of the mean pulmonary arterial pressure (mPAP), the pulmonary vascular resistance (PVR), the PaO2 /FiO2 ratio, the transpulmonary oxygen output (tpVO2 ), and the transpulmonary CO2 clearance (tpCO2 ). Mitochondrial homeostasis was investigated by measuring maximal oxidative capacity (Vmax ) and the coupling of phosphorylation to oxidation (ACR, acceptor control ratio) in lung biopsies. Inflammation and induction of primary immune response were assessed by measurement of tumor necrosis factor alpha (TNFα), interleukine-6 (IL-6) and receptor for advanced glycation endproducts (RAGE) in bronchoalveolar lavage fluid. Data were compared using repeated measures Anova. Pulmonary hemodynamics (mPAP: P = 0.69; PVR: P = 0.46), oxygenation (PaO2 /FiO2 : P = 0.56; tpVO2 : P = 0.46), CO2 diffusion (tpCO2 : P = 0.24), mitochondrial homeostasis (Vmax : P = 0.42; ACR: P = 0.8), and RAGE concentrations (P = 0.24) did not significantly change up to 8 h after cardiac arrest. TNFα and IL-6 were undetectable. Unaffected pulmonary hemodynamics, sustained oxygen and carbon dioxide diffusion, preserved mitochondrial homeostasis, and lack of inflammation suggest a long-lasting functional preservation of the graft with selective anterograde in situ pulmonary perfusion. © 2013 Steunstichting ESOT. Published by John Wiley & Sons Ltd.

Late summer temperature reconstruction based on tree-ring density for Sygera Mountain, southeastern Tibetan Plateau

NASA Astrophysics Data System (ADS)

Li, Mingyong; Duan, Jianping; Wang, Lily; Zhu, Haifeng

2018-04-01

Although several tree-ring density-based summer/late summer temperature reconstructions have been developed on the Tibetan Plateau (TP), the understanding of the local/regional characteristics of summer temperature fluctuations on a long-term scale in some regions is still limited. To improve our understanding in these aspects, more local or regional summer temperature reconstructions extending back over several centuries are required. In this study, a new mean latewood density (LWD) chronology from Abies georgei var. smithii from the upper tree line of Sygera Mountain on the southeastern TP was developed to reconstruct the late summer temperature variability since 1820 CE. The bootstrapped correlation analysis showed that the LWD chronology index was significantly and positively correlated with the late summer (August-September) mean temperatures (r1950-2008 = 0.63, p < 0.001) recorded at the nearest meteorological station and that this reconstruction has considerable potential to represent the late summer temperature variability at the regional scale. Our late summer temperature reconstruction revealed three obvious cold periods (i.e., 1872-1908, 1913-1937 and 1941-1966) and two relatively warm phases (i.e., 1821-1871 and 1970-2008) over the past two centuries. Comparisons of our reconstruction with other independent tree-ring-based temperature reconstructions, glacier fluctuations and historical documental records from neighboring regions showed good agreement in these relatively cold and warm intervals. Our reconstruction exhibits an overall increasing temperature trend since the 1960s, providing new evidence supporting the recent warming of the TP. Moreover, our results also indicate that the late summer temperature variability of Sygera Mountain on the southeastern TP has potential links with the Pacific Decadal Oscillation (PDO).

Retrieving Temperature Anomaly in the Global Subsurface and Deeper Ocean From Satellite Observations

NASA Astrophysics Data System (ADS)

Su, Hua; Li, Wene; Yan, Xiao-Hai

2018-01-01

Retrieving the subsurface and deeper ocean (SDO) dynamic parameters from satellite observations is crucial for effectively understanding ocean interior anomalies and dynamic processes, but it is challenging to accurately estimate the subsurface thermal structure over the global scale from sea surface parameters. This study proposes a new approach based on Random Forest (RF) machine learning to retrieve subsurface temperature anomaly (STA) in the global ocean from multisource satellite observations including sea surface height anomaly (SSHA), sea surface temperature anomaly (SSTA), sea surface salinity anomaly (SSSA), and sea surface wind anomaly (SSWA) via in situ Argo data for RF training and testing. RF machine-learning approach can accurately retrieve the STA in the global ocean from satellite observations of sea surface parameters (SSHA, SSTA, SSSA, SSWA). The Argo STA data were used to validate the accuracy and reliability of the results from the RF model. The results indicated that SSHA, SSTA, SSSA, and SSWA together are useful parameters for detecting SDO thermal information and obtaining accurate STA estimations. The proposed method also outperformed support vector regression (SVR) in global STA estimation. It will be a useful technique for studying SDO thermal variability and its role in global climate system from global-scale satellite observations.

How strong was the 2015/2016 El Niño event?

NASA Astrophysics Data System (ADS)

Iskandar, Iskhaq; Lestari, DeniOkta; Utari, PutriAdia; Sari, QurniaWulan; Setiabudidaya, Dedi; Mardiansyah, Wijaya; Supardi; Rozirwan

2018-04-01

On the interannual timescale, the Indonesian climate is strongly influenced by a coupled ocean-atmosphere modes in the tropical Pacific Ocean. During a warm phase (El Niño event), negative sea surface temperature anomalies (SSTA) in the western tropical Pacific lead to suppress convection activities causing reduce precipitation over the maritime continent. The situation is reverse during the cold season(La Niña event). In this study, the evolution of 2015/2016 El Niño event is evaluated based on the collected data by the Tropical Atmosphere Ocean/Triangle Trans-Ocean Buoy Network (TAO/TRITON) buoys. The results show that the evolution of the event has started in boreal spring (April – May 2015). It came to thepeak in boreal fall/winter (October – December 2015). The event lasted until boreal spring before it terminated in April/May 2016. In addition, the intensity of the event is classified as a strong event, and it is one of the strongest El Niño events during the last three decades.

TP53 regulates miRNA association with AGO2 to remodel the miRNA-mRNA interaction network.

PubMed

Krell, Jonathan; Stebbing, Justin; Carissimi, Claudia; Dabrowska, Aleksandra F; de Giorgio, Alexander; Frampton, Adam E; Harding, Victoria; Fulci, Valerio; Macino, Giuseppe; Colombo, Teresa; Castellano, Leandro

2016-03-01

DNA damage activates TP53-regulated surveillance mechanisms that are crucial in suppressing tumorigenesis. TP53 orchestrates these responses directly by transcriptionally modulating genes, including microRNAs (miRNAs), and by regulating miRNA biogenesis through interacting with the DROSHA complex. However, whether the association between miRNAs and AGO2 is regulated following DNA damage is not yet known. Here, we show that, following DNA damage, TP53 interacts with AGO2 to induce or reduce AGO2's association of a subset of miRNAs, including multiple let-7 family members. Furthermore, we show that specific mutations in TP53 decrease rather than increase the association of let-7 family miRNAs, reducing their activity without preventing TP53 from interacting with AGO2. This is consistent with the oncogenic properties of these mutants. Using AGO2 RIP-seq and PAR-CLIP-seq, we show that the DNA damage-induced increase in binding of let-7 family members to the RISC complex is functional. We unambiguously determine the global miRNA-mRNA interaction networks involved in the DNA damage response, validating them through the identification of miRNA-target chimeras formed by endogenous ligation reactions. We find that the target complementary region of the let-7 seed tends to have highly fixed positions and more variable ones. Additionally, we observe that miRNAs, whose cellular abundance or differential association with AGO2 is regulated by TP53, are involved in an intricate network of regulatory feedback and feedforward circuits. TP53-mediated regulation of AGO2-miRNA interaction represents a new mechanism of miRNA regulation in carcinogenesis. © 2016 Krell et al.; Published by Cold Spring Harbor Laboratory Press.

The origin of invasion of an alien frog species in Tibet, China.

PubMed

Wang, Supen; Fan, Liqing; Liu, Conghui; Li, Jiaqi; Gao, Xu; Zhu, Wei; Li, Yiming

2017-12-01

Identifying the origins of alien species has important implications for effectively controlling the spread of alien species. The black-spotted frog Pelophylax nigromaculatus , originally from East Asia, has become an alien species on the Tibetan Plateau (TP). In this study, we collected 300 individuals of P. nigromaculatus from 13 native regions and 2 invasive regions (including Nyingchi and Lhasa) on the TP. To identify the source region of the TP introductions, we sequenced portions of the mitochondrial cyt b gene. We sequenced a ∼600-bp portion of the mitochondrial cyt b gene to identify 69 haplotypes (124 polymorphic sites) in all sampled populations. According to the network results, we suggest that the P. nigromaculatus found on the TP was most likely originated from Chongqing by human introduction. Furthermore, we found that the genetic diversity was significantly lower for invasive than for native sites due to founder effects. Our study provides genetic evidence that this alien species invaded the cold environment of high elevations and expanded the distribution of P. nigromaculatus in China.

Gender-specific and gonadectomy-specific effects upon swim analgesia: role of steroid replacement therapy.

PubMed

Romero, M T; Cooper, M L; Komisaruk, B R; Bodnar, R J

1988-01-01

Both gender-specific and gonadectomy-specific effects have been observed for the analgesic responses following continuous and intermittent cold-water swims (CCWS and ICWS respectively): female rats display significantly less analgesia than males, and gonadectomized rats display significantly less analgesia than sham-operated controls. The present study evaluated the effects of steroid replacement therapy with testosterone propionate (TP: 2 mg/kg, SC) upon CCWS and ICWS analgesia on the tail-flick and jump tests and hypothermia in sham-operated or gonadectomized male and female rats. Thirty days following surgery, rats received either no treatment, a sesame oil vehicle or TP for 14 days prior to, and then during testing. Relative to the no treatment condition, repeated vehicle injections in sham-operated rats eliminated the gender-specific, but did not affect the gonadectomy-specific effects upon CCWS and ICWS analgesia. TP reversed the deficits in CCWS and ICWS analgesia observed in both castrated and ovariectomized rats on both pain tests. TP only potentiated CCWS analgesia in sham-operated males on the tail-flick test. TP potentiated CCWS and ICWS hypothermia in gonadectomized rats and in male sham-operated rats. These data indicate that gonadal steroids play a major modulatory role in the etiology of swim analgesia, and that the observed gender effects are sensitive to possible adaptational variables.

Temperature-precipitation relationship of the Common Era in northern Europe

NASA Astrophysics Data System (ADS)

Luoto, Tomi P.; Nevalainen, Liisa

2018-05-01

Due to the lack of knowledge on dynamics of the North Atlantic Oscillation (NAO) prior to the last millennium, synchronized records of air temperature and precipitation variability are needed to understand large-scale drivers of the hydroclimate. Here, we use completely synchronized paleolimnological proxy-based records of air temperature and effective precipitation from two Scandinavian lakes with ˜2000-year sediment profiles. We show that the relationship between air temperature and precipitation (T/P ratio) is synchronous in both study sites throughout the records suggesting warm and dry conditions at ˜300-1100 CE and cold and wet conditions at ˜1200-1900 CE. Owing to the significantly increased air temperatures, the most recent T/P ratio has again turned positive. During the first millennium of the Common Era, the T/P mimics patterns in Southern Oscillation index, whereas the second millennium shows response to the NAO index but is also concurrent with solar irradiance shifts. Since our T/P reconstruction is mostly linked with the NAO, we propose the T/P ratio as an indicator of the NAO. Our results from the coherent records provide first-time knowledge on the long-term temperature-precipitation relationship in Northern Europe that increase understanding of the comprehensive hydroclimate system in the region and the NAO dynamics also further back in time.

Determination of saleable product in finished cattle and beef carcasses utilizing bioelectrical impedance technology.

PubMed

Marchello, M J; McLennan, J E; Dhuyvetter, D V; Slanger, W D

1999-11-01

Two experiments were performed to develop prediction equations of saleable beef and to validate the prediction equations. In Exp. 1, 50 beef cattle were finished to typical slaughter weights, and multiple linear regression equations were developed to predict kilograms of trimmed boneless, retail product of live cattle, and hot and cold carcasses. A four-terminal bioelectrical impedance analyzer (BIA) was used to measure resistance (Rs) and reactance (Xc) on each animal and processed carcass. The IMPS cuts plus trim were weighed and recorded. Distance between detector terminals (Lg) and carcass temperature (Tp) at time of BIA readings were recorded. Other variables included live weight (BW), hot carcass weight (HCW), cold carcass weight (CCW), and volume (Lg2/Rs). Regression equations for predicting kilograms of saleable product were [11.87 + (.409 x BW) - (.335 x Lg) + (.0518 x volume)] for live (R2 = .80); [-58.83 + (.589 x HCW) - (.846 x Rs) + (1.152 x Xc) + (.142 x Lg) + (2.608 x Tp)] for hot carcass (R2 = .95); and [32.15 + (.633 x CCW) + (.33 x Xc) - (.83 x Lg) + (.677 x volume)] for cold carcass (R2 = .93). In Exp. 2, 27 beef cattle were finished in a manner similar to Exp. 1, and the prediction equations from Exp. 1 were used to predict the saleable product of these animals. The Pearson correlations between actual saleable product and the predictions based on live and cold carcass data were .91 and .95, respectively. The Spearman and Kendall rank correlations were .95 and .83, respectively, for the cold carcass data. These results provide a practical application of bioelectrical impedance for market-based pricing. They complement previous studies that assessed fat-free mass.

Atmospheric planetary wave response to external forcing

NASA Technical Reports Server (NTRS)

Stevens, D. E.; Reiter, E. R.

1985-01-01

The tools of observational analysis, complex general circulation modeling, and simpler modeling approaches were combined in order to attack problems on the largest spatial scales of the earth's atmosphere. Two different models were developed and applied. The first is a two level, global spectral model which was designed primarily to test the effects of north-south sea surface temperature anomaly (SSTA) gradients between the equatorial and midlatitude north Pacific. The model is nonlinear, contains both radiation and a moisture budget with associated precipitation and surface evaporation, and utilizes a linear balance dynamical framework. Supporting observational analysis of atmospheric planetary waves is briefly summarized. More extensive general circulation models have also been used to consider the problem of the atmosphere's response, especially in the horizontal propagation of planetary scale waves, to SSTA.

RSRM TP-H1148 Main Grain Propellant Crack Initiation Evaluation

NASA Technical Reports Server (NTRS)

Earnest, Todd E.

2005-01-01

Pressurized TP-HI 148 propellant fracture toughness testing was performed to assess the potential for initiation of visually undetectable cracks in the RSRM forward segment transition region during motor ignition. Two separate test specimens were used in this evaluation. Testing was performed in cold-gas and hot-fire environments, and under both static and dynamic pressurization conditions. Analysis of test results demonstrates safety factors against initiation of visually undetectable cracks in excess of 8.0. The Reusable Solid Rocket Motor (RSRM) forward segment is cast with PBAN propellant (TP-HI 148) to form T an 1 1-point star configuration that transitions to a tapered center perforated bore (see Figure 1). The geometry of the transition region between the fin valleys and the bore causes a localized area of high strain during horizontal storage. Updated analyses using worst-case mechanical properties at 40 F and improved modeling techniques indicated a slight reduction in safety margins over previous predictions. Although there is no history of strain induced cracks or flaws in the transition region propellant, a proactive test effort was initiated to better understand the implications of the new analysis, primarily the resistance of TP-H1148 propellant to crack initiation' during RSRM ignition.

Integration of Tibetan Plateau ice-core temperature records and the influence of atmospheric circulation on isotopic signals in the past century

NASA Astrophysics Data System (ADS)

Yang, Xiaoxin; Yao, Tandong; Joswiak, Daniel; Yao, Ping

2014-05-01

Temperature signals in ice-core δ18O on the Tibetan Plateau (TP), particularly in the central and southern parts, continue to be debated because of the large scale of atmospheric circulation. This study presents ten ice-core δ18O records at an annual resolution, with four (Malan, Muztagata, Guliya, and Dunde) in the northern, three (Puruogangri, Geladaindong, Tanggula) in the central and three (Noijin Kangsang, Dasuopu, East Rongbuk) in the southern TP. Integration shows commonly increasing trends in δ18O in the past century, featuring the largest one in the northern, a moderate one in the central and the smallest one in the southern TP, which are all consistent with ground-based measurements of temperature. The influence of atmospheric circulation on isotopic signals in the past century was discussed through the analysis of El Niño/Southern Oscillation (ENSO), and of possible connections between sea surface temperature (SST) and the different increasing trends in both ice-core δ18O and temperature. Particularly, El Niño and the corresponding warm Bay of Bengal (BOB) SST enhance the TP ice-core isotopic enrichment, while La Niña, or corresponding cold BOB SST, causes depletion. This thus suggests a potential for reconstructing the ENSO history from the TP ice-core δ18O.

Retrieved Products from Simulated Hyperspectral Observations of a Hurricane

NASA Technical Reports Server (NTRS)

Susskind, Joel; Kouvaris, Louis; Iredell, Lena; Blaisdell, John

2015-01-01

Retrievals were run using the AIRS Science Team Version-6 AIRS Only retrieval algorithm, which generates a Neural-Net first guess (T(sub s))(sup 0), (T(p))(sup 0), and (q(p))(sup 0) as a function of observed AIRS radiances. AIRS Science Team Neural-Net coefficients performed very well beneath 300 mb using the simulated radiances. This means the simulated radiances are very realistic. First guess and retrieved values of T(p) above 300 mb were biased cold, but both represented the model spatial structure very well. QC'd T(p) and q(p) retrievals for all experiments had similar accuracies compared to their own truth fields, and were roughly consistent with results obtained using real data. Spatial coverage of retrievals, as well as the representativeness of the spatial structure of the storm, improved dramatically with decreasing size of the instrument's FOV. We sent QC'd values of T(p) and q(p) to Bob Atlas at AOML for use as input to OSSE Data Assimilation experiments.

Performance of hybrid subsurface constructed wetland system for piggery wastewater treatment.

PubMed

Zhang, X; Inoue, T; Kato, K; Harada, J; Izumoto, H; Wu, D; Sakuragi, H; Ietsugu, H; Sugawara, Y

2016-01-01

The objective of this study was to evaluate performance of a hybrid constructed wetland (CW) built for high organic content piggery wastewater treatment in a cold region. The system consists of four vertical and one horizontal flow subsurface CWs. The wetland was built in 2009 and water quality was monitored from the outset. Average purification efficiency of this system was 95±5, 91±7, 89±8, 70±10, 84±15, 90±6, 99±2, and 93±16% for biochemical oxygen demand (BOD5), chemical oxygen demand (COD), total carbon (TC), total nitrogen (TN), ammonium-N (NH4-N), total phosphorus (TP), total coliform (T. Coliform), and suspended solids (SS), respectively during August 2010-December 2013. Pollutant removal rate was 15±18 g m(-2) d(-1), 49±52 g m(-2) d(-1), 6±4 g m(-2) d(-1), 7±5 g m(-2) d(-1), and 1±1 g m(-2) d(-1) for BOD5, COD, TN, NH4-N, and TP, respectively. The removal efficiency of BOD5, COD, NH4-N, and SS improved yearly since the start of operation. With respect to removal of TN and TP, efficiency improved in the first three years but slightly declined in the fourth year. The system performed well during both warm and cold periods, but was more efficient in the warm period. The nitrate increase may be attributed to a low C/N ratio, due to limited availability of carbon required for denitrification.

The link between Tibetan Plateau monsoon and Indian summer precipitation: a linear diagnostic perspective

NASA Astrophysics Data System (ADS)

Ge, Fei; Sielmann, Frank; Zhu, Xiuhua; Fraedrich, Klaus; Zhi, Xiefei; Peng, Ting; Wang, Lei

2017-12-01

The thermal forcing of the Tibetan Plateau (TP) is analyzed to investigate the formation and variability of Tibetan Plateau Summer Monsoon (TPSM), which affects the climates of the surrounding regions, in particular the Indian summer monsoon precipitation. Dynamic composites and statistical analyses indicate that the Indian summer monsoon precipitation is less/greater than normal during the strong/weak TPSM. Strong (weak) TPSM is associated with an anomalous near surface cyclone (anticyclone) over the western part of the Tibetan Plateau, enhancing (reducing) the westerly flow along its southern flank, suppressing (favoring) the meridional flow of warm and moist air from the Indian ocean and thus cutting (providing) moisture supply for the northern part of India and its monsoonal rainfall. These results are complemented by a dynamic and thermodynamic analysis: (i) A linear thermal vorticity forcing primarily describes the influence of the asymmetric heating of TP generating an anomalous stationary wave flux. Composite analysis of anomalous stationary wave flux activity (after Plumb in J Atmos Sci 42:217-229, 1985) strongly indicate that non-orographic effects (diabatic heating and/or interaction with transient eddies) of the Tibetan Plateau contribute to the generation of an anomalous cyclone (anti-cyclone) over the western TP. (ii) Anomalous TPSM generation shows that strong TPSM years are related to the positive surface sensible heating anomalies over the eastern TP favoring the strong diabatic heating in summer. While negative TPSM years are associated with the atmospheric circulation anomalies during the preceding spring, enhancing northerly dry-cold air intrusions into TP, which may weaken the condensational heat release in the middle and upper troposphere, leading to a weaker than normal summer monsoon over the TP in summer.

Aridity changes in the Tibetan Plateau in a warming climate

DOE PAGES

Gao, Yanhong; Li, Xia; Leung, Lai-Yung R.; ...

2015-03-10

Desertification in the Tibetan Plateau (TP) has drawn increasing attention in the recent decades. It has been postulated as a consequence of climate aridity due to the observed warming. This study quantifies the aridity changes in the TP and attributes the changes to different climatic factors. Using the ratio of P/PET (precipitation to potential evapotranspiration) as an aridity index to indicate changes in dryness and wetness in a given area, P/PET was calculated using observed records at 83 stations in the TP, with PET calculated using the Penman–Monteith (PM) algorithm. Spatial and temporal changes of P/PET in 1979-2011 are analyzed.more » Results show that stations located in the arid and semi-arid northwestern TP are becoming significantly wetter and stations in the semi-humid southeastern TP are becoming drier, though not significantly, in the recent three decades. The aridity change patterns are significantly correlated with precipitation, sunshine duration and diurnal temperature range changes at confidence level of 99.9% from two-tail t-test. Temporal correlations also confirm the significant correlation between aridity changes with the three variables, with precipitation being the most dominant driver of P/PET changes at interannual time scale. PET changes are insignificant but negatively correlated with P/PET in the cold season. In the warm season, however, correlation between PET changes and P/PET changes are significant at confidence level of 99.9% when the cryosphere melts near the surface. Significant correlation between wind speed changes and aridity changes occurs in limited locations and months. Consistency in the climatology pattern and linear trends in surface air temperature and precipitation calculated using station data, gridded data, and nearest grid-to-stations for the TP average and across sub-basins indicate the robustness of the trends despite the large spatial heterogeneity in the TP that challenge climate monitoring.« less

Variability in precipitation in a watershed in the altiplano, Peru and modes of variation

NASA Astrophysics Data System (ADS)

Mazzarino, M.; Brown, C. M.

2012-12-01

This research examines system linkages between climate, water availability, pasture availability, camelids (llamas and alpacas) and indigenous herders in an Andean watershed in southern Peru. In this region, extreme meteorological events such as drought and flood, occur often and have the potential to negatively impact herding livelihoods. Predictability in the system is paramount to reducing risks associated with these events. In the altiplano, a large portion of variability in precipitation has been attributed to the influence of El Nino Southern Oscillation (ENSO). In light of climate change and observations by herders, this research returns to the question of teleconnections in the altiplano. We use December through March precipitation totals obtained from eight meteorological stations for 43 years (1964-2006) and sea surface temperatures (SSTs) in the equatorial Pacific and Atlantic to characterize the hydroclimatology in the watershed and determine modes of variability. Following principal components analysis, prevailing periodicities in regional precipitation were determined using wavelet analysis and spatial correlation and regression analysis were used to determine the relationship between SST anomalies (SSTA's) and precipitation events in the watershed. Results suggest a non-linear and non-stationary mode of variability. We draw three conclusions from the results: 1) Positive precipitation extremes are dominated by an ENSO signal in the Nino 2 region; 2) Post 1987 there is a weak relationship, if any, between anomalously dry years in the precipitation record and SSTA's in the equatorial Pacific; 3) There is a stronger relationship (inverse) between precipitation in the region and SSTA's in the tropical Atlantic than previously believed.

WES feedback and the Atlantic Meridional Mode: observations and CMIP5 comparisons

NASA Astrophysics Data System (ADS)

Amaya, Dillon J.; DeFlorio, Michael J.; Miller, Arthur J.; Xie, Shang-Ping

2017-09-01

The Atlantic Meridional Mode (AMM) is the dominant mode of tropical SST/wind coupled variability. Modeling studies have implicated wind-evaporation-SST (WES) feedback as the primary driver of the AMM's evolution across the Atlantic basin; however, a robust coupling of the SST and winds has not been shown in observations. This study examines observed AMM growth, propagation, and decay as a result of WES interactions. Investigation of an extended maximum covariance analysis shows that boreal wintertime atmospheric forcing generates positive SST anomalies (SSTA) through a reduction of surface evaporative cooling. When the AMM peaks in magnitude during spring and summer, upward latent heat flux anomalies occur over the warmest SSTs and act to dampen the initial forcing. In contrast, on the southwestern edge of the SSTA, SST-forced cross-equatorial flow reduces the strength of the climatological trade winds and provides an anomalous latent heat flux into the ocean, which causes southwestward propagation of the initial atmosphere-forced SSTA through WES dynamics. Additionally, the lead-lag relationship of the ocean and atmosphere indicates a transition from an atmosphere-forcing-ocean regime in the northern subtropics to a highly coupled regime in the northern tropics that is not observed in the southern hemisphere. CMIP5 models poorly simulate the latitudinal transition from a one-way interaction to a two-way feedback, which may explain why they also struggle to reproduce spatially coherent interactions between tropical Atlantic SST and winds. This analysis provides valuable insight on how meridional modes act as links between extratropical and tropical variability and focuses future research aimed at improving climate model simulations.

Impacts of SST anomalies in the Indian-Pacific basin on Northwest Pacific tropical cyclone activities during three super El Niño years

NASA Astrophysics Data System (ADS)

Zhan, Ruifen; Chen, Baode; Ding, Yihui

2018-01-01

This study investigated the impact of sea surface temperature (SST) in several important areas of the Indian-Pacific basin on tropical cyclone (TC) activity over the western North Pacific (WNP) during the developing years of three super El Niño events (1982, 1997, and 2015) based on observations and numerical simulations. During the super El Niño years, TC intensity was enhanced considerably, TC days increased, TC tracks mostly recurved along the coasts, and fewer TCs made landfall in China. These characteristics are similar to the strong ENSO-TC relationship but further above the climatological means than in strong El Niño years. It indicates that super El Niño events play a dominant role in the intensities and tracks of WNP TCs. However, there were clear differences in both numbers and positions of TC genesis among the different super El Niño years. These features could be attributed to the collective impact of SST anomalies (SSTAs) in the tropical central-eastern Pacific and East Indian Ocean (EIO) and the SST gradient (SSTG) between the southwestern Pacific and the western Pacific warm pool. During 2015, the EIO SSTA was extremely warm and the anomalous anticyclone in the western WNP was enhanced, resulting in fewer TCs than normal. In 1982, the EIO SSTA and spring SSTG showed negative anomalies, followed by an increased anomalous cyclone in the western WNP and equatorial vertical wind shear. This intensified the conversion of eddy kinetic energy from large-scale flows, favorable for the westward shift of TC genesis. Consequently, anomalous TC activities during the super El Niño years resulted mainly from combined SSTA impacts of different key areas over the Indian-Pacific basin.

Coupled Modes over Indian Ocean at Sub-seasonal time Scales and its Prediction

NASA Astrophysics Data System (ADS)

Jung, E.; Kirtman, B. P.

2014-12-01

Sub-seasonal variability over the Indian Ocean, such as Madden-Julian Oscillation impacts weather and climate globally. However, the prediction of tropical sub-seasonal variability (TSV) remains a challenge, and understanding air-sea interactions on TSV time-scales is likely to be an important part of the prediction problem. The purpose of this paper is to examine the predictability of sub-seasonal variability in the tropical Indo-Pacific region. The analysis emphasizes on variability associated with coupled air-sea interactions in observational estimates, and how well these coupled modes are simulated and predicted within the context of a 30-year retrospective forecast experiment with a state-of-the-art atmosphere-ocean coupled model. The analysis shows that Sea Surface Temperature anomalies (SSTA) over the Indian Ocean tend to precede precipitation anomalies by 7-11 days with maximum amplitude over the Arabian Sea and the Bay of Bengal for summer and along the Seychelles-Chagos Thermocline Ridge (SCTR) region for winter. Though these coupled modes are captured by the models, the forecasts fail to predict its evolution. Based on the diagnosis of these coupled modes, we introduce a SCTR-SST index and an index that measures the modulation of the low-frequency amplitude (LFAM) of sub-seasonal SSTA variability over SCTR as a way to predict the coupled modes. Based on correlation with the observed variability, SCTR-SST has forecast skill of about 45 days over the Indian Ocean. However the sub-seasonal SSTAs in the predictions and the observational estimates do not have any direct ENSO tele-connection. In contrast, the LFAM of the sub-seasonal SSTA variance over SCTR is strongly correlated with ENSO, suggesting enhanced sub-seasonal variance on seasonal time-scales is potentially predictable.

Storage of Fruits and Vegetables in Refrigerator Increases their Phenolic Acids but Decreases the Total Phenolics, Anthocyanins and Vitamin C with Subsequent Loss of their Antioxidant Capacity

PubMed Central

Patel, Nilesh J.; Talati, Jayant G.

2017-01-01

It is of paramount importance for consumers, scientists and industrialists to understand how low-temperature storage of food items affects their bioactive compounds and properties. This study evaluated the effects of cold storage on total phenolics (TP), phenolic acids profile (PA), total anthocyanins (TA), total ascorbic acid (Vit. C) and antioxidant activity (AA) of 19 fruits and vegetables, collected from local Indian markets and stored in refrigerator (4 °C) during 15 days. Content of TP was highest in dill and amaranth and decreased (up to 29.67%) with storage. Leafy vegetables (amaranth, dill, onion, fenugreek and spinach) contained higher amounts of the 12 PA revealed by UPLC-UV; ellagic, gallic, sinapic and vanillic acids levels were the highest; chlorogenic acid (ρ = 0.423), syringic acid (ρ = 0.403) and sinapic acid (ρ = 0.452) mostly correlated with TP; and the PA increased during storage. Highest contents of Vit C estimated by AOAC, DCPIP and DNP methods were found in amaranth, dill and pomegranate, and decreased with storage. Pomegranate showed highest TA levels and low-temperature storage did not significantly increase TA, which was the largest contributor of TP in fruits and vegetables (ρ = 0.661). Storage induced a drastic decrease of AA, which mostly correlated with TP (ρ = 0.808, 0.690 and 0.458 for DPPH, ABTS and FRAP assays, respectively). Spearman’s correlation confirmed by principal component analysis demonstrated that dill, pomegranate and amaranth had the highest overall antioxidant capacity, whereas orange juice and carrot showed the lowest. The results provide support for a key-role of TP, followed by Vit. C and TA in antioxidant capacity of fruits and vegetables, which could be interesting dietary sources of natural antioxidants for prevention of diseases caused by oxidative stress. PMID:28737734

Storage of Fruits and Vegetables in Refrigerator Increases their Phenolic Acids but Decreases the Total Phenolics, Anthocyanins and Vitamin C with Subsequent Loss of their Antioxidant Capacity.

PubMed

Galani, Joseph H Y; Patel, Jalpesh S; Patel, Nilesh J; Talati, Jayant G

2017-07-24

It is of paramount importance for consumers, scientists and industrialists to understand how low-temperature storage of food items affects their bioactive compounds and properties. This study evaluated the effects of cold storage on total phenolics (TP), phenolic acids profile (PA), total anthocyanins (TA), total ascorbic acid (Vit. C) and antioxidant activity (AA) of 19 fruits and vegetables, collected from local Indian markets and stored in refrigerator (4 °C) during 15 days. Content of TP was highest in dill and amaranth and decreased (up to 29.67%) with storage. Leafy vegetables (amaranth, dill, onion, fenugreek and spinach) contained higher amounts of the 12 PA revealed by UPLC-UV; ellagic, gallic, sinapic and vanillic acids levels were the highest; chlorogenic acid (ρ = 0.423), syringic acid (ρ = 0.403) and sinapic acid (ρ = 0.452) mostly correlated with TP; and the PA increased during storage. Highest contents of Vit C estimated by AOAC, DCPIP and DNP methods were found in amaranth, dill and pomegranate, and decreased with storage. Pomegranate showed highest TA levels and low-temperature storage did not significantly increase TA, which was the largest contributor of TP in fruits and vegetables (ρ = 0.661). Storage induced a drastic decrease of AA, which mostly correlated with TP (ρ = 0.808, 0.690 and 0.458 for DPPH, ABTS and FRAP assays, respectively). Spearman's correlation confirmed by principal component analysis demonstrated that dill, pomegranate and amaranth had the highest overall antioxidant capacity, whereas orange juice and carrot showed the lowest. The results provide support for a key-role of TP, followed by Vit. C and TA in antioxidant capacity of fruits and vegetables, which could be interesting dietary sources of natural antioxidants for prevention of diseases caused by oxidative stress.

Feedback process responsible for intermodel diversity of ENSO variability

NASA Astrophysics Data System (ADS)

An, Soon-Il; Heo, Eun Sook; Kim, Seon Tae

2017-05-01

The origin of the intermodel diversity of the El Niño-Southern Oscillation (ENSO) variability is investigated by applying a singular value decomposition (SVD) analysis between the intermodel tropical Pacific sea surface temperature anomalies (SSTA) variance and the intermodel ENSO stability index (BJ index). The first SVD mode features an ENSO-like pattern for the intermodel SSTA variance (74% of total variance) and the dominant thermocline feedback (TH) for the BJ index (51%). Intermodel TH is mainly modified by the intermodel sensitivity of the zonal thermocline gradient response to zonal winds over the equatorial Pacific (βh), and the intermodel βh is correlated higher with the intermodel off-equatorial wind stress curl anomalies than the equatorial zonal wind stress anomalies. Finally, the intermodel off-equatorial wind stress curl is associated with the meridional shape and intensity of ENSO-related wind patterns, which may cause a model-to-model difference in ENSO variability by influencing the off-equatorial oceanic Rossby wave response.

The relative contributions of tropical Pacific sea surface temperatures and atmospheric internal variability to the recent global warming hiatus

NASA Astrophysics Data System (ADS)

Deser, Clara; Guo, Ruixia; Lehner, Flavio

2017-08-01

The recent slowdown in global mean surface temperature (GMST) warming during boreal winter is examined from a regional perspective using 10-member initial-condition ensembles with two global coupled climate models in which observed tropical Pacific sea surface temperature anomalies (TPAC SSTAs) and radiative forcings are specified. Both models show considerable diversity in their surface air temperature (SAT) trend patterns across the members, attesting to the importance of internal variability beyond the tropical Pacific that is superimposed upon the response to TPAC SSTA and radiative forcing. Only one model shows a close relationship between the realism of its simulated GMST trends and SAT trend patterns. In this model, Eurasian cooling plays a dominant role in determining the GMST trend amplitude, just as in nature. In the most realistic member, intrinsic atmospheric dynamics and teleconnections forced by TPAC SSTA cause cooling over Eurasia (and North America), and contribute equally to its GMST trend.

Role of Tropical Atlantic SST Variability as a Modulator of El Nino Teleconnections

NASA Technical Reports Server (NTRS)

Ham, Yoo-Geun; Sung, Mi-Kyung; An, Soon-II; Schubert, Siegfried D.; Kug, Jong-Seong

2014-01-01

The present study suggests that the off-equatorial North Atlantic (NATL) SST warming plays a significant role in modulating El Niño teleconnection and its impact on the North Atlantic and European regions. The El Niño events accompanied by NATL SST warming exhibit south-north dipole pattern over the Western Europe to Atlantic, while the ENSO teleconnection pattern without NATL warming exhibits a Rossby wave-like pattern confined over the North Pacific and western Atlantic. Especially, the El Niño events with NATL warming show positive (negative) geopotential-height anomalies over the North Atlantic (Western Europe) which resemble the negative phase of the NAO. Consistently, it is shown using a simple statistical model that NATL SSTA in addition to the tropical Pacific SSTA leads to better prediction on regional climate variation over the North Atlantic and European regions. This role of NATL SST on ENSO teleconnection is also validated and discussed in a long term simulation of coupled global circulation model (CGCM).

Satellite-observed snow cover variations over the Tibetan Plateau for the period 2001-2014

NASA Astrophysics Data System (ADS)

Long, D.; Chen, X.

2016-12-01

Snow is an integral component of the global climate system. Owing to its high albedo and thermal and water storage properties, snow has important linkages and feedbacks through its influence on surface energy and moisture fluxes, clouds, precipitation, hydrology, and atmospheric circulation. As the "Roof of the World" and the "Third Pole" with the highest mountains in middle latitudes, the Tibetan Plateau (TP) is one of the most hot spots in climate change and hydrological studies, in which seasonal snow cover is a critical aspect. Unlike large-scale snow cover and regional-scale glaciers over other cryospheric regions, changes in snow cover over the TP has been largely unknown due mostly to the quality of observations. Based on improved MODIS daily snow cover products, this study aims to quantify the distribution and changes in snow cover over the TP for the period 2001 to 2014. Results show that the spatial distribution of changes in snow cover fraction (SCF) over the 14-year study period exhibited a general negative trend over the TP driven primarily by increasing land surface temperature (LST), except some areas of the upper Golden-Sanded River and upper Brahmaputra River basins. However, decreased LST and increased precipitation in the accumulation season (September to the following February) resulted in increased SCF in the accumulation season, coinciding with large-scale cold snaps and heavy snowfall events at middle latitudes. Detailed analyses of the intra-annual variability of SCF in the TP regions show an increase in SCF in the accumulation season but a decrease in SCF in the melting season (March to August), indicating that the intra-annual amplitude of SCF increased during the study period and more snow cover was released as snowmelt in the spring season.

Nitrogen and phosphorus transport between Fourleague Bay, LA, and the Gulf of Mexico: The role of winter cold fronts and Atchafalaya River discharge

USGS Publications Warehouse

Perez, B.C.; Day, J.W.; Justic, D.; Twilley, R.R.

2003-01-01

Nutrient fluxes were measured between Fourleague Bay, a shallow Louisiana estuary, and the Gulf of Mexico every 3 h between February 1 and April 30, 1994 to determine how high velocity winds associated with cold fronts and peak Atchafalaya River discharge influenced transport. Net water fluxes were ebb-dominated throughout the study because of wind forcing and high volumes of water entering the northern Bay from the Atchafalaya River. Flushing time of the Bay averaged <8 days; however, more rapid flushing occurred in response to northerly winds with approximately 56% of the volume of the Bay exported to the Gulf in 1 day during the strongest flushing event. Higher nitrate + nitrite (NO2+ NO3), total nitrogen (TN), and total phosphorus (TP) concentrations were indicative of Atchafalaya River input and fluxes were greater when influenced by high velocity northerly winds associated with frontal passage. Net exports of NO2 + NO3, TN, and TP were 43.5, 98.5, and 13.6 g s-1, respectively, for the 89-day study. An average of 10.6 g s-1 of ammonium (NH4) was exported to the Gulf over the study; however, concentrations were lower when associated with riverine influence and wind-driven exports suggesting the importance of biological processes. Phosphate (PO4) fluxes were nearly balanced over the study with fairly stable concentrations indicating a well-buffered system. The results indicate that the high energy subsidy provided by natural pulsing events such as atmospheric cold fronts and seasonal river discharge are efficient mechanisms of nutrient delivery to adjacent wetlands and nearshore coastal ecosystems and are important in maintaining coastal sustainability. ?? 2003 Elsevier Ltd. All rights reserved.

Predictability of rainfall and teleconnections patterns influencing on Southwest Europe from sea surfaces temperatures

NASA Astrophysics Data System (ADS)

Lorenzo, M. N.; Iglesias, I.; Taboada, J. J.; Gómez-Gesteira, M.; Ramos, A. M.

2009-04-01

This work assesses the possibility of doing a forecast of rainfall and the main teleconnections patterns that influences climate in Southwest Europe by using sea surface temperature anomalies (SSTA). The area under study is located in the NW Iberian Peninsula. This region has a great oceanic influence on its climate and has an important dependency of the water resources. In this way if the different SST patterns are known, the different rainfall situations can be predicted. On the other hand, the teleconnection patterns, which have strong weight on rainfall, are influenced by the SSTA of different areas. In the light of this, the aim of this study is to explore the relationship between global SSTAs, rainfall and the main teleconnection patterns influencing on Europe. The SST data with a 2.0 degree resolution was provided by the NOAA/OAR/ESRL PSD, Boulder, Colorado, USA. A monthly averaged data from 1 January 1951 through December 2006 was considered. The monthly precipitation data from 1951-2006 were obtained from the database CLIMA of the University of Santiago de Compostela with data from the Meteorological State Agency (AEMET) and the Regional Government of Galicia. The teleconnection indices were taken of the Climate Prediction Center of the NOAA between 1950 and 2006. A monthly and seasonal study was analysed considering up to three months of delay in the first case and up to four seasons of delay in the second case. The Pearson product-moment correlation coefficient r was considered to quantify linear associations between SSTA and precipitation and/or SSTA and teleconnection indices. A test for field-significance was applied considering the properties of finiteness and interdependence of the spatial grid to avoid spurious correlations. Analysing the results obtained with the global SSTA and the teleconnection indices, a great number of ocean regions with high correlations can be found. The spatial patterns show very high correlations with Indian Ocean waters which could be related with the Monsoon. Another area with high correlation is Equatorial Pacific Ocean, the area related with the ENSO phenomenon. These SSTAs could be used to forecast rainfall anomalies in spring season in the area of NW Iberian Peninsula. Results show that La Niña years almost always announces dry spring in NW Iberian Peninsula. Nevertheless, El Niño years do not preclude the appearance of wet spring. Because of the progress that has been made in its prediction, the relation between ENSO and climate in NW Iberian Peninsula is of interest with respect to potential seasonal predictability and the results can be extended to the south west of Europe. [1] Lorenzo, M.N. and J. J. Taboada (2005). Influences of atmospheric variability on freshwater input in Galician Rías in winter. Journal of Atmospheric and Ocean Science Vol 10, No 4, 377-387. [2] Lorenzo, M.N. I. Iglesias, J.J. Taboada and M. Gómez-Gesteira. Relationship between monthly rainfall in NW Iberian Peninsula and North Atlantic sea surface temperature. International Journal of Climatology. (Submitted to International Journal of Climatology). [3] Philips, I.D. and J. Thorpe (2006): Icelandic precipitation-North Atlantic sea-surface temperature associations. International Journal of Climatology 26: 1201-1221.

Assessment of future climate change impacts on nonpoint source pollution in snowmelt period for a cold area using SWAT.

PubMed

Wang, Yu; Bian, Jianmin; Zhao, Yongsheng; Tang, Jie; Jia, Zhuo

2018-02-05

The source area of Liao River is a typical cold region in northeastern China, which experiences serious problems with agricultural nonpoint source pollution (NPS), it is important to understand future climate change impacts on NPS in the watershed. This issue has been investigated by coupling semi distributed hydrological model (SWAT), statistical downscaling model (SDSM) and global circulation model (GCMs). The results show that annual average temperature would rise by 2.1 °C (1.3 °C) in the 2080 s under scenario RCP8.5 (RCP4.5), and annual precipitation would increase by 67 mm (33 mm). The change in winter temperature and precipitation is most significant with an increase by 0.23 °C/10a (0.17 °C/10a) and 1.94 mm/10a (2.78 mm/10a). The future streamflow, TN and TP loads would decrease by 19.05% (10.59%), 12.27% (8.81%) and 10.63% (6.11%), respectively. Monthly average streamflow, TN and TP loads would decrease from March to November, and increase from December to February. This is because the increased precipitation and temperature in winter, which made the spring snowpack melting earlier. These study indicate the trends of nonpoint source pollution during the snowmelt period under climate change conditions, accordingly adaptation measures will be necessary.

Coping Mechanisms Used by Rural Principals. SSTA Research Centre Report #95-13.

ERIC Educational Resources Information Center

SSTA Research in Brief, 1995

1995-01-01

A survey examined the use of coping mechanisms by rural Saskatchewan principals and principals' perceptions of the effectiveness of coping mechanisms used. A modified form of the Ways of Coping questionnaire was mailed to 110 rural principals throughout Saskatchewan (Canada); 48 usable responses were returned. The questionnaire focused on eight…

Simulation of Tropical Rainfall Variability

NASA Astrophysics Data System (ADS)

Bader, J.; Latif, M.

2002-12-01

The impact of sea surface temperature (SST) - especially the role of the tropical Atlantic meridional SST gradient and the El Nino-Southern Oscillation - on precipitation is investigated with the atmospheric general circulation model ECHAM4/T42. Ensemble experiments - driven with observed SST - show that Atlantic SST has a significant influence on precipitation over West Africa and northeast Brazil. SST sensitivity experiments were performed in which the climatological SST was enhanced or decreased by one Kelvin in certain ocean areas. Changing SST in the eastern tropical Atlantic caused only significant changes along the Guinea Coast, with a positive anomaly (SSTA) increasing rainfall and a negative SSTA reducing it. The response was nearly linear. Changing SST in other ocean areas caused significant changes over West Africa, especially in the Sahel area. The response is found to be non linear, with only negative SSTA leading to significant reduction in Sahel rainfall. Also, the impact of the SSTAs from the different ocean regions was not additive with respect to the rainfall. The influence of SST on precipitation over northeast Brazil (Nordeste) was also investigated. Three experiments were performed in which the climatological SST was enhanced/decreased or decreased/enhanced by one Kelvin in the North/South Atlantic and increased by two Kelvin in the Nino3 ocean area. All experiments caused significant changes over Nordeste, with an enhanced/reduced SST gradient in the Atlantic increasing/reducing rainfall. The response was nearly linear. The main effect of the Atlantic SST gradient was a shift of the ITCZ, caused by trade wind changes. The ''El Nino'' event generates a significant reduction in Nordeste rainfall. A significant positive SLP anomaly occurs in northeast Brazil which may be associated with the descending branch of the Walker circulation. Also a significant positive SLP over the Atlantic from 30S to 10N north occurs. This results in a reduced SLP gradient from the subtropical highs to the equator and a weakening of the trade winds.

Potential impact of the May Southern Hemisphere annular mode on the Indian summer monsoon rainfall

NASA Astrophysics Data System (ADS)

Dou, Juan; Wu, Zhiwei; Zhou, Yefan

2017-04-01

El Niño-Southern Oscillation (ENSO) is probably a most important external forcing to Indian summer monsoon (ISM) rainfall (ISMR), yet the observed ENSO-ISMR relationship has become weak in recent years. It's essential to explore other predominant modes of variability which can contribute to the ISMR. As the leading mode of the variability in Southern Hemisphere (SH) extratropical atmospheric circulation, the SH annular mode (SAM) has potential influence both on the northern and southern hemispheric climate. The present study investigates the relationship between the SAM and ISMR. It is found that the May SAM exhibits a significant positive correlation with the monsoon precipitation over the Indian sub-continent and the adjacent areas in JunetJuly (JJ). Observational and numerical evidences indicate that the May SAM anomaly can trigger a South Indian Ocean dipole (SIOD) sea surface temperature anomaly (SSTA) through air-sea interactions. The SIOD SSTA persisting into the following months of JJ excites abnormal meridional circulation and modulates the low-level cross-equatorial flow. Accordingly, the ascending (or descending) motion and water vapor transportation are enhanced (or suppressed), which favors more (or less) precipitation over the Indian sub-continent and the adjacent areas. In fact, the SIOD SSTA plays an "ocean bridge" role to "prolong" the influence of the May SAM to the subsequent season and in turn impacts on the ISMR. Moreover, an empirical model is established to forecast the JJ ISMR strength based on the ENSO, Indian Ocean Dipole (IOD) and May SAM. The hindcast is carried out for the period 1979-2014, and performs better than the multimodel ensemble mean (MME) obtained from the Development of a European MME system for seasonal to interannual prediction (DEMETER) project. Since all these predictors can be monitored in real time before the early boreal summer, the empirical model might provide a practical real-time forecast tool for predicting ISMR variations.

Potential impact of the May Southern Hemisphere annular mode on the Indian summer monsoon rainfall

NASA Astrophysics Data System (ADS)

Dou, Juan; Wu, Zhiwei; Zhou, Yefan

2017-08-01

El Niño-Southern Oscillation (ENSO) is probably a most important external forcing to Indian summer monsoon (ISM) rainfall (ISMR), yet the observed ENSO-ISMR relationship has become weak in recent years. It's essential to explore other predominant modes of variability which can contribute to the ISMR. As the leading mode of the variability in Southern Hemisphere (SH) extratropical atmospheric circulation, the SH annular mode (SAM) has potential influence both on the northern and southern hemispheric climate. The present study investigates the relationship between the SAM and ISMR. It is found that the May SAM exhibits a significant positive correlation with the monsoon precipitation over the Indian sub-continent and the adjacent areas in June-July (JJ). Observational and numerical evidences indicate that the May SAM anomaly can trigger a South Indian Ocean dipole (SIOD) sea surface temperature anomaly (SSTA) through air-sea interactions. The SIOD SSTA persisting into the following months of JJ excites abnormal meridional circulation and modulates the low-level cross-equatorial flow. Accordingly, the ascending (or descending) motion and water vapor transportation are enhanced (or suppressed), which favors more (or less) precipitation over the Indian sub-continent and the adjacent areas. In fact, the SIOD SSTA plays an "ocean bridge" role to "prolong" the influence of the May SAM to the subsequent season and in turn impacts on the ISMR. Moreover, an empirical model is established to forecast the JJ ISMR strength based on the ENSO, Indian Ocean Dipole and May SAM. The hindcast is carried out for the period 1979-2014, and performs better than the multimodel ensemble mean (MME) obtained from the Development of a European MME system for seasonal to interannual prediction (DEMETER) project. Since all these predictors can be monitored in real time before the early boreal summer, the empirical model might provide a practical real-time forecast tool for predicting ISMR variations.

Bibliography on Cold Regions Science and Technology. Volume 47, Part 1, 1993

DTIC Science & Technology

1993-09-01

54 refs. • DLC TP884.A3 D87 1989 Tundra. Plant ecology. Plant physiology. Plant tissues.tions. Biomass. ice cover effect. Ice optics. Algae. Concrete...1992. 89(1). p.24-31. 15 refs. ty. Chemical properties. Nuclear power. Freeze 91i92. This included providing the fundamental life Plante . P.. Pleau. R...Arora. R., etal, Plant physiology. Aug. 1992.99(4). photography. North Sea. Wetlands sewage treatment tested in the north. p. 1 56 2 .1568. 30 refs

Spatio-temporal variability of vertical gradients of major meteorological observations around the Tibetan Plateau

NASA Astrophysics Data System (ADS)

Guo, X.; Wang, L.; Tian, L.

2015-12-01

The near-surface air temperature lapse rate (TLR), wind speed gradient (WSG), and precipitation gradient (PG) provide crucial parameters used in models of mountain climate and hydrology. The complex mountain terrain and vast area of the Tibetan Plateau (TP) make such factors particularly important. With daily data from 161 meteorological stations over the past 43 years (1970-2012), we analyse the spatio-temporal variations of TLRs, WSGs, and PGs over and around TP, derived using linear regression methods and dividing the study area into zones based on spatial variations. Results of this study include: (1) The observed TLR varies from -0.46 to -0.73 ∘C (100 m) -1, with averaged TLRs of -0.60,-0.62, and -0.59 ∘C (100 m) -1 for Tmax, Tmin,and Tmean , respectively. The averaged TLR is slightly less than the global mean of -0.65 ∘C (100 m) -1 . The spatial variability of TLR relates to climate conditions, wherein the TLR increases in dry conditions and in cold months (October-April), while it lessens in humid regions and during warm months (May-September). (2) The estimated annual WSG ranges from 0.07 to 0.17m s -1 (100 m) -1. Monthly WSGs show a marked seasonal shift, in which higher WSGs can be explained by the high intensity of prevailing wind. (3) Positive summer PGs vary from 12.08 in the central TP to 26.14 mm (100 m) -1 in northeastern Qinghai and the southern TP, but a reverse gradient prevails in Yunnan and parts of Sichuan Province. (4) The regional warming over TP is more evident in winter, and Tmin demonstrated the most prominent warming compared with Tmax and Tmean. Environments at high elevations experience more rapid changes in temperatures (Tmax, Tmin,and Tmean) than those at low elevations, which is especially true in winter and for Tmin. Furthermore, inter-annual variation of TLRs is linked to elevation-dependent warming.

Senior Science Enrichment Modules. S.S.T.A. Research Centre Report No. 58.

ERIC Educational Resources Information Center

Fedorak, Allen; And Others

Presented is a set of learning modules intended for teaching science to students in grades eleven and twelve. Each module incorporates problem solving using the scientific viewpoint and emphasizing the interface between science and society. The fifteen modules presented include the following topics: group dynamics; the value of science; a puzzle…

The Systemic-Structural Theory of Activity: Applications to the Study of Human Work

ERIC Educational Resources Information Center

Bedny, Gregory Z.; Harris, Steven Robert

2005-01-01

This article offers an introduction to the central concepts and principles of the Systemic-Structural Theory of Activity (SSTA), an activity-theoretical approach specifically tailored to the analysis and design of human work. In activity theory, cognition is understood both as a process and as a structured system of actions. Building on the…

Farm Stress and School Practice. SSTA Research Centre Report #95-12.

ERIC Educational Resources Information Center

SSTA Research in Brief, 1995

1995-01-01

Interviews with 12 principals of K-12 schools in rural Saskatchewan examined practices enacted in 1992-93 to lessen the effects of the farm economic crisis on students. A seven-section literature review describes the financial, personal, family, and community components of the farm crisis in Canada and the United States and provides an overview of…

Cold Fusion at Hotspots

NASA Astrophysics Data System (ADS)

Natland, J. H.

2009-12-01

Olivine-liquid FeO-MgO (OLFM) equilibria is often assumed and used to estimate eruptive (To) and melting (potential) temperatures (TP) of primitive magmas and their MgO contents at spreading ridges and linear volcanic chains. The technique involves incremental addition of melt calculated to be in equilibrium with successively more magnesian olivine until an olivine of “mantle” composition is reached. Incremental olivine addition depends on the assumption that that this olivine and the host liquid lie along a single liquid line of descent determined by crystallization of olivine and no other mineral; i.e., the parental liquid was formally picritic in composition. This assumption can be questioned on three grounds, which may vary in importance from place to place, but at least one of which always appears to be operative: 1) most picrites are hybrids between primitive and differentiated magmas, the latter expressing cotectic crystallization of olivine, plagioclase and/or clinopyroxene (e.g., Baffin-West Greenland, Hawaii, Samoa), and have higher Fe/Mg than primitive magma, making estimates of To and TP too high; 2) the rocks themselves contain phenocrysts of plagioclase (e.g., Iceland) and/or clinopyroxene (e.g., Samoa) as well as olivine; 3) not even the most primitive magmas, evidenced by mineral associations in accumulative magmatic xenoliths (dunite, wehrlite, olivine clinopyroxene; many examples) indicate stages of crystallization involving olivine by itself. An alternative approach that uses liquid compositions to estimate compositions of Cr-spinel (Poustovetov and Roeder, 2000) predicts no natural Cr-spinel that crystallized at temperature >1400C or pressure 1.5 GPa either in picrites or xenoliths at any of these localities; no parental liquid had MgO > 16%. Spinel predicted from high-MgO (>20%) parental liquids postulated by OLFM matches nothing in nature. Natural glass in Samoan harzburgite xenoliths is mainly differentiated basalt, hawaiite and mugearite with average melt temperature of ~1100C, the same temperature as given by Ca-in-orthopyroxene of the harzburgites. Cold ambient mantle draws heat from ascending magma, forcing differentiation at depth. Magma with TP greater by 200C than primitive basalt at spreading ridges does not exist at any of these places. TP does not constrain temperature of the mantle below the depth of melt extraction. High and variable 3He/4He at all these places may result from volatile incorporation from old harzburgite through which magmas must ascend. Poustovetov, A., and Roeder, P.L., 2000. Canad. Min. 39: 309-317.

Indian and Metis Education: Parents as Partners. SSTA Forum Report (Saskatoon, Saskatchewan, Canada, October 14-15, 1993). Report #93-10.

ERIC Educational Resources Information Center

Saskatchewan School Trustees Association, Regina.

This report summarizes a forum held in Saskatchewan, Canada to discuss Indian and Metis education, with a particular focus on increasing parent involvement. Parent participation may be placed on a continuum from communication between school and parents to autonomous control of the school by parents and community. Demographic data show that…

SPAR thermal analysis processors reference manual, system level 16. Volume 1: Program executive. Volume 2: Theory. Volume 3: Demonstration problems. Volume 4: Experimental thermal element capability. Volume 5: Programmer reference

NASA Technical Reports Server (NTRS)

Marlowe, M. B.; Moore, R. A.; Whetstone, W. D.

1979-01-01

User instructions are given for performing linear and nonlinear steady state and transient thermal analyses with SPAR thermal analysis processors TGEO, SSTA, and TRTA. It is assumed that the user is familiar with basic SPAR operations and basic heat transfer theory.

The tropospheric biennial oscillation defined by a biennial mode of sea surface temperature and its impact on the atmospheric circulation and precipitation in the tropical eastern Indo-western Pacific region

NASA Astrophysics Data System (ADS)

Kim, Jinju; Kim, Kwang-Yul

2016-10-01

Temporal and spatial patterns of anomalous atmospheric circulation and precipitation over the Indo-Pacific region are analyzed in conjunction with the Tropospheric Biennial Oscillation as represented by the biennial mode of sea surface temperature anomalies (SSTA). The biennial components of key variables are identified independently of other variability via CSEOF analysis. Then, its impact on the Asian-Australian monsoon is examined. The biennial mode exhibits a seasonally distinctive atmospheric response over the tropical eastern Indo-western Pacific (EIWP) region (90°-150°E, 20°S-20°N). In boreal summer, local meridional circulation is a distinguishing characteristic over the tropical EIWP region, whereas a meridionally expanded branch of intensified zonal circulation develops in austral summer. Temporally varying evolution and distinct timing of SSTA phase transition in the Indian and Pacific Oceans is considered a main factor for this variation of circulation in the tropical EIWP region. The impact of the biennial mode is not the same between the two seasons, with different impacts over ocean areas in Asian monsoon and Australian monsoon regions.

Multiplex Amplification Coupled with COLD-PCR and High Resolution Melting Enables Identification of Low-Abundance Mutations in Cancer Samples with Low DNA Content

PubMed Central

Milbury, Coren A.; Chen, Clark C.; Mamon, Harvey; Liu, Pingfang; Santagata, Sandro; Makrigiorgos, G. Mike

2011-01-01

Thorough screening of cancer-specific biomarkers, such as DNA mutations, can require large amounts of genomic material; however, the amount of genomic material obtained from some specimens (such as biopsies, fine-needle aspirations, circulating-DNA or tumor cells, and histological slides) may limit the analyses that can be performed. Furthermore, mutant alleles may be at low-abundance relative to wild-type DNA, reducing detection ability. We present a multiplex-PCR approach tailored to amplify targets of interest from small amounts of precious specimens, for extensive downstream detection of low-abundance alleles. Using 3 ng of DNA (1000 genome-equivalents), we amplified the 1 coding exons (2-11) of TP53 via multiplex-PCR. Following multiplex-PCR, we performed COLD-PCR (co-amplification of major and minor alleles at lower denaturation temperature) to enrich low-abundance variants and high resolution melting (HRM) to screen for aberrant melting profiles. Mutation-positive samples were sequenced. Evaluation of mutation-containing dilutions revealed improved sensitivities after COLD-PCR over conventional-PCR. COLD-PCR improved HRM sensitivity by approximately threefold to sixfold. Similarly, COLD-PCR improved mutation identification in sequence-chromatograms over conventional PCR. In clinical specimens, eight mutations were detected via conventional-PCR-HRM, whereas 12 were detected by COLD-PCR-HRM, yielding a 33% improvement in mutation detection. In summary, we demonstrate an efficient approach to increase screening capabilities from limited DNA material via multiplex-PCR and improve mutation detection sensitivity via COLD-PCR amplification. PMID:21354058

Pacific-North American teleconnection and North Pacific Oscillation: historical simulation and future projection in CMIP5 models

NASA Astrophysics Data System (ADS)

Chen, Zheng; Gan, Bolan; Wu, Lixin; Jia, Fan

2017-09-01

Based on reanalysis datasets and as many as 35 CMIP5 models, this study evaluates the capability of climate models to simulate the spatiotemporal features of Pacific-North American teleconnection (PNA) and North Pacific Oscillation (NPO) in the twentieth century wintertime, and further investigates their responses to greenhouse warming in the twenty-first century. Analysis reveals that while the majority (80%) of models reasonably simulate either the geographical distribution or the amplitude of PNA/NPO pattern, only half of models can well capture both features in space. As for the temporal features, variabilities of PNA and NPO in most models are biased toward higher amplitude. Additionally, most models simulate the interannual variabilities of PNA and NPO, qualitatively consistent with the observation, whereas models generally lack the capability to reproduce the decadal (20-25 years) variability of PNA. As the climate warms under the strongest future warming scenario, the PNA intensity is found to be strengthened, whereas there is no consensus on the direction of change in the NPO intensity among models. The intensification of positive PNA is primarily manifested in the large deepening of the North Pacific trough, which is robust as it is 2.3 times the unforced internal variability. By focusing on the tropical Pacific Ocean, we find that the multidecadal evolution of the North Pacific trough intensity (dominating the PNA intensity evolution) is closely related to that of the analogous trough in the PNA-like teleconnection forced by sea surface temperature anomalies (SSTa) in the tropical central Pacific (CP) rather than the tropical eastern Pacific (EP). Such association is also found to act under greenhouse warming: that is, the strengthening of the PNA-like teleconnection induced by the CP SSTa rather than the EP SSTa is a driving force for the intensification of PNA. This is in part owing to the robust enhancement of the tropical precipitation response to the CP SST variation. Indeed, further inspection suggests that models with stronger intensification of the CP SST variability and its related tropical precipitation response tend to have larger deepening magnitude of the North Pacific trough associated with the PNA variability.

Why did the 2015/16 El Niño Fail to Bring Excessive Precipitation to California?

NASA Astrophysics Data System (ADS)

Jong, B. T.; Ting, M.; Seager, R.; Lee, D. E.

2016-12-01

California has experienced severe drought in recent years posing great challenges to water resources, agriculture, and land management. El Niño, as the prime sources of seasonal to interannual climate predictability, offers the potential of alleviation of drought in California. Here, El Niño's impacts on California winter precipitation are examined. Our results, based on the observations during 1901-2010, show that El Niño's influence on precipitation strengthens from early to late winter even as El Niño weakens. The cause of the nonlinear relationship between sea surface temperature anomaly (SSTA) amplitude and teleconnection strength is the late winter warming of the climatological mean SST over the tropical eastern Pacific, allowing more active and eastward extending tropical deep convection anomaly. The 2015/16 El Niño, one of the strongest events in recent history, did not bring the heavy precipitation to California anticipated based on model forecasts and experience with the previous two strong El Niños, 1982/83 and 1997/98. North American Multi-Model Ensemble (NMME) 3-month average forecasts of SST from February 1 2016, models overestimated the Niño3 SSTA, compared to what actually occurred and, consistently, forecast heavier than observed California precipitation. The too high Niño3 SSTA drove too strong deep convection anomalies in the eastern tropical Pacific, triggering a too strong teleconnection that made the forecast California precipitation too wet. Thus, the faster than forecast decay in Niño3 SST anomalies at the end of the 2015/16 El Niño is one possible reason why the event failed to bring excess precipitation to California in the late winter. Controlled GCM experiments support this hypothesis and show that the teleconnection forced by the multimodel mean forecast of 2016 February-March-April SSTAs is stronger than the one forced by the observed SSTAs. Within the NMME those models that more correctly forecast the decay of El Niño 2015/16 also more correctly forecast modest precipitation anomalies over California.

Pacific-North American teleconnection and North Pacific Oscillation: historical simulation and future projection in CMIP5 models

NASA Astrophysics Data System (ADS)

Chen, Zheng; Gan, Bolan; Wu, Lixin; Jia, Fan

2018-06-01

Based on reanalysis datasets and as many as 35 CMIP5 models, this study evaluates the capability of climate models to simulate the spatiotemporal features of Pacific-North American teleconnection (PNA) and North Pacific Oscillation (NPO) in the twentieth century wintertime, and further investigates their responses to greenhouse warming in the twenty-first century. Analysis reveals that while the majority (80%) of models reasonably simulate either the geographical distribution or the amplitude of PNA/NPO pattern, only half of models can well capture both features in space. As for the temporal features, variabilities of PNA and NPO in most models are biased toward higher amplitude. Additionally, most models simulate the interannual variabilities of PNA and NPO, qualitatively consistent with the observation, whereas models generally lack the capability to reproduce the decadal (20-25 years) variability of PNA. As the climate warms under the strongest future warming scenario, the PNA intensity is found to be strengthened, whereas there is no consensus on the direction of change in the NPO intensity among models. The intensification of positive PNA is primarily manifested in the large deepening of the North Pacific trough, which is robust as it is 2.3 times the unforced internal variability. By focusing on the tropical Pacific Ocean, we find that the multidecadal evolution of the North Pacific trough intensity (dominating the PNA intensity evolution) is closely related to that of the analogous trough in the PNA-like teleconnection forced by sea surface temperature anomalies (SSTa) in the tropical central Pacific (CP) rather than the tropical eastern Pacific (EP). Such association is also found to act under greenhouse warming: that is, the strengthening of the PNA-like teleconnection induced by the CP SSTa rather than the EP SSTa is a driving force for the intensification of PNA. This is in part owing to the robust enhancement of the tropical precipitation response to the CP SST variation. Indeed, further inspection suggests that models with stronger intensification of the CP SST variability and its related tropical precipitation response tend to have larger deepening magnitude of the North Pacific trough associated with the PNA variability.

Internal Dynamics and Boundary Forcing Characteristics Associated with Interannual Variability of the Asian Summer Monsoon

NASA Technical Reports Server (NTRS)

Lau, K.- M.; Kim, K.-M.; Yang, S.

1998-01-01

In this paper, we present a description of the internal dynamics and boundary forcing characteristics of two major components of the Asian summer monsoon (ASM), i.e., the South Asian (SAM) and the Southeast-East Asian monsoon (SEAM). The description is based on a new monsoon-climate paradigm in which the variability of ASM is considered as the outcome of the interplay of a "fast" and an "intermediate" monsoon subsystem, under the influenced of the "slow" varying external forcings. Two sets of regional monsoon indices derived from dynamically consistent rainfall and wind data are used in this study. For SAM, the internal dynamics is represented by that of a "classical" monsoon system where the anomalous circulation is governed by Rossby-wave dynamics, i.e., generation of anomalous vorticity induced by an off-equatorial heat source is balanced by planetary vorticity advection. On the other hand, the internal dynamics of SEAM is characterized by a "hybrid" monsoon system featuring multi-cellular meridional circulation over the East Asian section, extending from the deep tropics to midlatitudes. These meridional-cells link tropical heating to extratropical circulation system via the East Asian jetstream, and are responsible for the characteristic occurrences of zonally oriented anomalous rainfall patterns over East Asian and the subtropical western Pacific. In the extratropical regions, the major upper level vorticity balance is by anomalous vorticity advection and generation by the anomalous divergent circulation. A consequence of this is that compared to SAM, the SEAM is associated with stronger teleconnection patterns to regions outside the ASM. A strong SAM is linked to basin-scale sea surface temperature (SST) fluctuation with significant signal in the equatorial eastern Pacific. During the boreal spring SST warming in the Arabian Sea and the subtropical western Pacific may lead to a strong SAM. For SEAM, interannual variability is tied to SSTA over the Sea of Japan and the South China Sea regions, while the linkage to equatorial basin-scale SSTA is weak at best. A large scale SSTA dipole with warming (cooling) in the subtropical central (eastern) Pacific foreshadows a strong SEAM.

Trophic magnification of PCBs and its relationship to the octanol-water partition coefficient

USGS Publications Warehouse

Walters, D.M.; Mills, M.A.; Cade, B.S.; Burkard, L.P.

2011-01-01

We investigated polychlorinated biphenyl (PCB) bioaccumulation relative to octanol-water partition coefficient (KOW) and organism trophic position (TP) at the Lake Hartwell Superfund site (South Carolina). We measured PCBs (127 congeners) and stable isotopes (??15N) in sediment, organic matter, phytoplankton, zooplankton, macroinvertebrates, and fish. TP, as calculated from ??15N, was significantly, positively related to PCB concentrations, and food web trophic magnification factors (TMFs) ranged from 1.5-6.6 among congeners. TMFs of individual congeners increased strongly with log KOW, as did the predictive power (r2) of individual TP-PCB regression models used to calculate TMFs. We developed log KOW-TMF models for eight food webs with vastly different environments (freshwater, marine, arctic, temperate) and species composition (cold- vs warmblooded consumers). The effect of KOW on congener TMFs varied strongly across food webs (model slopes 0.0-15.0) because the range of TMFs among studies was also highly variable. We standardized TMFs within studies to mean = 0, standard deviation (SD) = 1 to normalize for scale differences and found a remarkably consistent KOW effect on TMFs (no difference in model slopes among food webs). Our findings underscore the importance of hydrophobicity (as characterized by KOW) in regulating bioaccumulation of recalcitrant compounds in aquatic systems, and demonstrate that relationships between chemical KOW and bioaccumulation from field studies are more generalized than previously recognized. ?? This article not subject to U.S. Copyright. Published 2011 by the American Chemical Society.

A six hundred-year annual minimum temperature history for the central Tibetan Plateau derived from tree-ring width series

NASA Astrophysics Data System (ADS)

He, Minhui; Yang, Bao; Datsenko, Nina M.

2014-08-01

The recent unprecedented warming found in different regions has aroused much attention in the past years. How temperature has really changed on the Tibetan Plateau (TP) remains unknown since very limited high-resolution temperature series can be found over this region, where large areas of snow and ice exist. Herein, we develop two Juniperus tibetica Kom. tree-ring width chronologies from different elevations. We found that the two tree-ring series only share high-frequency variability. Correlation, response function and partial correlation analysis indicate that prior year annual (January-December) minimum temperature is most responsible for the higher belt juniper radial growth, while more or less precipitation signal is contained by the tree-ring width chronology at the lower belt and is thus excluded from further analysis. The tree growth-climate model accounted for 40 % of the total variance in actual temperature during the common period 1957-2010. The detected temperature signal is further robustly verified by other results. Consequently, a six century long annual minimum temperature history was firstly recovered for the Yushu region, central TP. Interestingly, the rapid warming trend during the past five decades is identified as a significant cold phase in the context of the past 600 years. The recovered temperature series reflects low-frequency variability consistent with other temperature reconstructions over the whole TP region. Furthermore, the present recovered temperature series is associated with the Asian monsoon strength on decadal to multidecadal scales over the past 600 years.

Trophic magnification of PCBs and Its relationship to the octanol-water partition coefficient.

PubMed

Walters, David M; Mills, Marc A; Cade, Brian S; Burkard, Lawrence P

2011-05-01

We investigated polychlorinated biphenyl (PCB) bioaccumulation relative to octanol-water partition coefficient (K(OW)) and organism trophic position (TP) at the Lake Hartwell Superfund site (South Carolina). We measured PCBs (127 congeners) and stable isotopes (δ¹⁵N) in sediment, organic matter, phytoplankton, zooplankton, macroinvertebrates, and fish. TP, as calculated from δ¹⁵N, was significantly, positively related to PCB concentrations, and food web trophic magnification factors (TMFs) ranged from 1.5-6.6 among congeners. TMFs of individual congeners increased strongly with log K(OW), as did the predictive power (r²) of individual TP-PCB regression models used to calculate TMFs. We developed log K(OW)-TMF models for eight food webs with vastly different environments (freshwater, marine, arctic, temperate) and species composition (cold- vs warmblooded consumers). The effect of K(OW) on congener TMFs varied strongly across food webs (model slopes 0.0-15.0) because the range of TMFs among studies was also highly variable. We standardized TMFs within studies to mean = 0, standard deviation (SD) = 1 to normalize for scale differences and found a remarkably consistent K(OW) effect on TMFs (no difference in model slopes among food webs). Our findings underscore the importance of hydrophobicity (as characterized by K(OW)) in regulating bioaccumulation of recalcitrant compounds in aquatic systems, and demonstrate that relationships between chemical K(OW) and bioaccumulation from field studies are more generalized than previously recognized.

Detrended Partial-Cross-Correlation Analysis: A New Method for Analyzing Correlations in Complex System

PubMed Central

Yuan, Naiming; Fu, Zuntao; Zhang, Huan; Piao, Lin; Xoplaki, Elena; Luterbacher, Juerg

2015-01-01

In this paper, a new method, detrended partial-cross-correlation analysis (DPCCA), is proposed. Based on detrended cross-correlation analysis (DCCA), this method is improved by including partial-correlation technique, which can be applied to quantify the relations of two non-stationary signals (with influences of other signals removed) on different time scales. We illustrate the advantages of this method by performing two numerical tests. Test I shows the advantages of DPCCA in handling non-stationary signals, while Test II reveals the “intrinsic” relations between two considered time series with potential influences of other unconsidered signals removed. To further show the utility of DPCCA in natural complex systems, we provide new evidence on the winter-time Pacific Decadal Oscillation (PDO) and the winter-time Nino3 Sea Surface Temperature Anomaly (Nino3-SSTA) affecting the Summer Rainfall over the middle-lower reaches of the Yangtze River (SRYR). By applying DPCCA, better significant correlations between SRYR and Nino3-SSTA on time scales of 6 ~ 8 years are found over the period 1951 ~ 2012, while significant correlations between SRYR and PDO on time scales of 35 years arise. With these physically explainable results, we have confidence that DPCCA is an useful method in addressing complex systems. PMID:25634341

A New Technique to Observe ENSO Activity via Ground-Based GPS Receivers

NASA Astrophysics Data System (ADS)

Suparta, Wayan; Iskandar, Ahmad; Singh, Mandeep Singh Jit

In an attempt to study the effects of global climate change in the tropics for improving global climate model, this paper aims to detect the ENSO events, especially El Nino phase by using ground-based GPS receivers. Precipitable water vapor (PWV) obtained from the Global Positioning System (GPS) Meteorology measurements in line with the sea surface temperature anomaly (SSTa) are used to connect their response to El Niño activity. The data gathered from four selected stations over the Southeast Asia, namely PIMO (Philippines), KUAL (Malaysia), NTUS (Singapore) and BAKO (Indonesia) for the year of 2009/2010 were processed. A strong correlation was observed for PIMO station with a correlation coefficient of -0.90, significantly at the 99 % confidence level. In general, the relationship between GPS PWV and SSTa at all stations on a weekly basis showed with a negative correlation. The negative correlation indicates that during the El Niño event, the PWV variation was in decreased trend. Decreased trend of PWV value is caused by a dry season that affected the GPS signals in the ocean-atmospheric coupling. Based on these promising results, we can propose that the ground-based GPS receiver is capable used to monitor ENSO activity and this is a new prospective method that previously unexplored.

A Controlled Agitation Process for Improving Quality of Canned Green Beans during Agitation Thermal Processing.

PubMed

Singh, Anika; Pratap Singh, Anubhav; Ramaswamy, Hosahalli S

2016-06-01

This work introduces the concept of a controlled agitation thermal process to reduce quality damage in liquid-particulate products during agitation thermal processing. Reciprocating agitation thermal processing (RA-TP) was used as the agitation thermal process. In order to reduce the impact of agitation, a new concept of "stopping agitations after sufficient development of cold-spot temperature" was proposed. Green beans were processed in No. 2 (307×409) cans filled with liquids of various consistency (0% to 2% CMC) at various frequencies (1 to 3 Hz) of RA-TP using a full-factorial design and heat penetration results were collected. Corresponding operator's process time to impart a 10-min process lethality (Fo ) and agitation time (AT) were calculated using heat penetration results. Accordingly, products were processed again by stopping agitations as per 3 agitation regimes, namely; full time agitation, equilibration time agitation, and partial time agitation. Processed products were photographed and tested for visual quality, color, texture, breakage of green beans, turbidity, and percentage of insoluble solids in can liquid. Results showed that stopping agitations after sufficient development of cold-spot temperatures is an effective way of reducing product damages caused by agitation (for example, breakage of beans and its leaching into liquid). Agitations till one-log temperature difference gave best color, texture and visual product quality for low-viscosity liquid-particulate mixture and extended agitations till equilibration time was best for high-viscosity products. Thus, it was shown that a controlled agitation thermal process is more effective in obtaining high product quality as compared to a regular agitation thermal process. © 2016 Institute of Food Technologists®

Gd Ba Cu O bulk superconductors fabricated by a seeded infiltration growth technique under reduced oxygen partial pressure

NASA Astrophysics Data System (ADS)

Iida, K.; Babu, N. H.; Shi, Y. H.; Cardwell, D. A.; Murakami, M.

2006-06-01

Single-grain Gd-Ba-Cu-O (GdBCO) bulk superconductors have been grown by a seeded infiltration and growth (SIG) technique under a 1% O2+N2 atmosphere using a generic MgO-doped Nd-Ba-Cu-O (MgO-NdBCO) seed placed on the sample surface at room temperature (the so-called the cold-seeding method). Partial melting of the MgO-NdBCO seeds fabricated in air under notionally identical thermal processing conditions, however, limited the reliability of this bulk GdBCO single-grain process. The observed seed decomposition is attributed to the dependence of the peritectic temperature Tp of MgO-doped Nd1+xBa2-xCu3Oy solid solution (MgO-doped Nd-123ss, where ss indicates solid solution) compounds on both oxygen partial pressure during the melt process and the level of solid solution (x). The peritectic decomposition temperature of MgO-doped Nd-123ss, with x ranging from 0 to 0.5 under p(O2) = 1.00 atm, was observed to remain constant at 1120 °C. Tp was observed to decrease linearly as a function of solid solution level, on the other hand, under oxygen partial pressures of both p(O2) = 0.21 and 0.01 atm. Based on these results, MgO-doped NdBCO seed crystals should be grown under reduced oxygen partial pressure in order to obtain a stable MgO-doped NdBCO seed crystal suitable for cold-seeding processes of large-grain (RE)BCO bulk superconductors (where RE is a rare earth element).

The National Space Science and Technology Center's Education and Public Outreach Program

NASA Astrophysics Data System (ADS)

Cox, G. N.; Denson, R. L.

2004-12-01

The objective of the National Space Science and Technology Center's (NSSTC) Education and Public Outreach program (EPO) is to support K-20 education by coalescing academic, government, and business constituents awareness, implementing best business/education practices, and providing stewardship over funds and programs that promote a symbiotic relationship among these entities, specifically in the area of K-20 Science, Technology, Engineering, and Mathematics (STEM) education. NSSTC EPO Program's long-term objective is to showcase its effective community-based integrated stakeholder model in support of STEM education and to expand its influence across the Southeast region for scaling ultimately across the United States. The Education and Public Outreach program (EPO) is coordinated by a supporting arm of the NSSTC Administrative Council called the EPO Council (EPOC). The EPOC is funded through federal, state, and private grants, donations, and in-kind contributions. It is comprised of representatives of NSSTC Research Centers, both educators and scientists from the Alabama Space Science and Technology Alliance (SSTA) member institutions, the Alabama Space Grant Consortium and the NASA Marshall Space Flight Center's (MSFC) Education Office. Through its affiliation with MSFC and the SSTA - a consortium of Alabama's research universities that comprise the NSSTC, EPO fosters the education and development of the next generation of Alabama scientists and engineers by coordinating activities at the K-20 level in cooperation with the Alabama Department of Education, the Alabama Commission on Higher Education, and Alabama's businesses and industries. The EPO program's primary objective is to be Alabama's premiere organization in uniting academia, government, and private industry by way of providing its support to the State and Federal Departments of Education involved in systemic STEM education reform, workforce development, and innovative uses of technology. The NSSTC EPO is poised to be a leader in this field because of its direct support to agency's accountable for America's educational systems, and for its synergistic relationships across the integrated stakeholder community. This includes Alabama's NASA facility, USRA, the SSTA's seven research universities, businesses and industries, and the Alabama Math, Science and Technology Education Coalition. In addition to traditional outreach methodologies, the EPO uses the unique resources of the NSSTC to assist in dissolving the boundaries in education among academia, government, and industry and to foster a more collaborative environment in support of STEM education reform.

Exploring the water storage changes in the largest lake (Selin Co) over the Tibetan Plateau during 2003-2012 from a basin-wide hydrological modeling

NASA Astrophysics Data System (ADS)

Zhou, Jing; Wang, Lei; Zhang, Yinsheng; Guo, Yanhong

2016-04-01

Lake water storage change (DSw) is an important indicator of the hydrologic cycle and greatly influences lake expansion/shrinkage over the Tibetan Plateau (TP). Accurate estimation of DSw will contribute to improved understanding of lake variations in the TP. Based on a water balance, this study explored the variations of DSw for the Lake Selin Co (the largest closed lake on the TP) during 2003-2012 using the Water and Energy Budget-based Distributed Hydrological Model (WEB-DHM) together with two different evapotranspiration (ET) algorithms (the Penman-Monteith method and a simple sublimation estimation approach for water area in unfrozen and frozen period). The contributions of basin discharge and climate causes to the DSw are also quantitatively analyzed. The results showed that WEB-DHM could well reproduce daily discharge, the spatial pattern, and basin-averaged values of MODIS land surface temperature (LST) during nighttime and daytime. Compared with the ET reference values estimated from the basin-wide water balance, our ET estimates showed better performance than three global ET products in reproducing basin-averaged ET. The modeled ET at point scale matches well with short-term in situ daily measurements (RMSE=0.82 mm/d). Lake inflows and precipitation over the water area had stronger relationships with DSw in the warm season and monthly scale, whereas evaporation from the water area had remarkable effects on DSw in the cold season. The total contribution of the three factors to DSw was about 90%, and accounting for 49.5%, 22.1%, and 18.3%, respectively.

The Mass-dependent Star Formation Histories of Disk Galaxies: Infall Model Versus Observations

NASA Astrophysics Data System (ADS)

Chang, R. X.; Hou, J. L.; Shen, S. Y.; Shu, C. G.

2010-10-01

We introduce a simple model to explore the star formation histories of disk galaxies. We assume that the disk originate and grows by continuous gas infall. The gas infall rate is parameterized by the Gaussian formula with one free parameter: the infall-peak time tp . The Kennicutt star formation law is adopted to describe how much cold gas turns into stars. The gas outflow process is also considered in our model. We find that, at a given galactic stellar mass M *, the model adopting a late infall-peak time tp results in blue colors, low-metallicity, high specific star formation rate (SFR), and high gas fraction, while the gas outflow rate mainly influences the gas-phase metallicity and star formation efficiency mainly influences the gas fraction. Motivated by the local observed scaling relations, we "construct" a mass-dependent model by assuming that the low-mass galaxy has a later infall-peak time tp and a larger gas outflow rate than massive systems. It is shown that this model can be in agreement with not only the local observations, but also with the observed correlations between specific SFR and galactic stellar mass SFR/M * ~ M * at intermediate redshifts z < 1. Comparison between the Gaussian-infall model and the exponential-infall model is also presented. It shows that the exponential-infall model predicts a higher SFR at early stage and a lower SFR later than that of Gaussian infall. Our results suggest that the Gaussian infall rate may be more reasonable in describing the gas cooling process than the exponential infall rate, especially for low-mass systems.

Study of Cold Fusion Reactions Using Collective Clusterization Approach

NASA Astrophysics Data System (ADS)

Kaur, Gurjit; Sandhu, Kirandeep; Sharma, Manoj K.

2017-10-01

Within the framework of the dynamical cluster decay model (DCM), the 1n evaporation cross-sections ({σ }1n) of cold fusion reactions (Pb and Bi targets) are calculated for {Z}{CN}=104-113 superheavy nuclei. The calculations are carried out in the fixed range of excitation energy {E}{CN}* =15+/- 1 {MeV}, so that the comparative analysis of reaction dynamics can be worked out. First of all, the fission barriers (B f ) and neutron separation energies ({S}1n) are estimated to account the decreasing cross-sections of cold fusion reactions. In addition to this, the importance of hot optimum orientations of β 2i-deformed nuclei over cold one is explored at fixed angular momentum and neck-length parameters. The hot optimum orientations support all the target-projectile (t,p) combinations, which are explored experimentally in the cold fusion reactions. Some new target-projectile combinations are also predicted for future exploration. Further, the 1n cross-sections are addressed for {Z}{CN}=104-113 superheavy nuclei at comparable excitation energies which show the decent agrement with experimental data upto {Z}{CN}=109 nuclei. Finally, to understand the dynamics of higher-Z superheavy nuclei, the cross-sections are also calculated at maximum available energies around the Coulomb barrier and the effect of non-sticking moment of inertia ({I}{NS}) is also investigated at these energies. Supported by the Council of Scientific and Industrial Research (CSIR), in the Form of Research Project Grant No. 03(1341)/15/EMR-II, and to DST, New Delhi, for INSPIRE-Fellowship Grant No. DST/INSPIRE/03/2015/000199

Seasonal differences of model predictability and the impact of SST in the Pacific

NASA Astrophysics Data System (ADS)

Lang, X. M.; Wang, H. J.

2005-01-01

Both seasonal potential predictability and the impact of SST in the Pacific on the forecast skill over China are investigated by using a 9-level global atmospheric general circulation model developed at the Institute of Atmospheric Physics under the Chinese Academy of Sciences (IAP9L-ACCM). For each year during 1970 to 1999, the ensemble consists of seven integrations started from consecutive observational daily atmospheric fields and forced by observational monthly SST. For boreal winter, spring and summer, the variance ratios of the SST-forced variability to the total variability and the differences in the spatial correlation coefficients of seasonal mean fields in special years versus normal years are computed respectively. It follows that there are slightly inter-seasonal differences in the model potential predictability in the Tropics. At northern middle and high latitudes, prediction skill is generally low in spring and relatively high either in summer for surface air temperature and middle and upper tropospheric geopotential height or in winter for wind and precipitation. In general, prediction skill rises notably in western China, especially in northwestern China, when SST anomalies (SSTA) in the Ni (n) over tildeo-3 region are significant. Moreover, particular attention should be paid to the SSTA in the North Pacific (NP) if one aims to predict summer climate over the eastern part of China, i.e., northeastern China, North China and southeastern China.

Connection between the Silk Road Pattern in July and the following January temperature over East Asia

NASA Astrophysics Data System (ADS)

He, Shengping; Liu, Yang; Wang, Huijun

2017-04-01

This study investigates a cross-seasonal influence of the Silk Road Pattern (SRP) in July and discusses the related mechanism. Both the reanalysis and observational datasets indicate that the July SRP is closely related to the following January temperature over East Asia during 1958/59-2001/02. Linear regression results reveal that, following a higher-than-normal SRP index in July, the Siberian high, Aleutian low, Urals high, East Asian trough, and meridional shear of the East Asian jet intensify significantly in January. Such atmospheric circulation anomalies are favorable for northerly wind anomalies over East Asia, leading to more southward advection of cold air and causing a decrease in temperature. Further analysis indicates that the North Pacific sea surface temperature anomalies (SSTAs) might play a critical role in storing the anomalous signal of the July SRP. The significant SSTAs related to the July SRP weaken in October and November, re-emerge in December, and strengthen in the following January. Such an SSTA pattern in January can induce a surface anomalous cyclone over North Pacific and lead to dominant convergence anomalies over northwestern Pacific. Correspondingly, significant divergence anomalies appear, collocated in the upper-level troposphere in situ. Due to the advection of vorticity by divergent wind, which can be regarded as a wave source, a stationary Rossby wave originates from North Pacific and propagates eastward to East Asia, leading to temperature anomalies through its influence on the large-scale atmospheric circulation.

Age-related differences of semen quality, seminal plasma, and spermatozoa antioxidative and oxidative stress variables in bulls during cold and warm periods of the year.

PubMed

Vince, S; Žura Žaja, I; Samardžija, M; Majić Balić, I; Vilić, M; Đuričić, D; Valpotić, H; Marković, F; Milinković-Tur, S

2018-03-01

The aims of this study were to determine the presence and quantities of antioxidative status and oxidative stress (OS) variables in the seminal plasma and spermatozoa of bulls of varying age during cold and warm periods of the year, and to establish the correlation of these variables with semen quality parameters. The study was conducted on two groups each comprising nine Simmental bulls: one group contained younger animals (aged 2 to 4 years) and the second older animals (aged 5 to 10 years). Semen samples were collected using an artificial vagina for biochemical analysis. Seminal plasma and spermatozoa activities of total superoxide dismutase (TSOD), manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), catalase (CAT), selenium-dependent glutathione peroxidase, reduced glutathione and concentrations of total protein (TP), thiobarbituric acid reactive substances (TBARS) and protein carbonyl content (PCC) were determined. Several antioxidants in seminal plasma were also determined: total glutathione peroxidase (TGSH-Px), selenium-independent glutathione peroxidase (Non-SeGSH-Px), uric acid, albumins (ALB) and alkaline phosphatase (ALP). Significantly higher spermatozoa motility was observed during the cold v. warm period, and a significantly higher volume and total number of spermatozoa per ejaculate was observed in older than in younger bulls. Significantly higher values of ALP, TP and ALB were found in seminal plasma of older bulls than in younger bulls during the warm period. The seminal plasma of younger bulls showed significantly higher activities of TSOD, MnSOD, CuZnSOD, TGSH-Px and Non-SeGSH-Px. Younger bulls had significantly higher PCC concentration and activity of CAT in seminal plasma than older bulls during the cold period. Significantly higher concentrations of PCC and TBARS, and activities of TSOD, MnSOD and CuZnSOD were established in spermatozoa of the younger than in older bulls during the warm period. It could be concluded that antioxidative and OS variables differ significantly depending on bull age and time of year. Younger bulls were more sensitive to elevated ambient temperatures during the warm period, when the higher enzymatic antioxidative protection in seminal plasma and spermatozoa were insufficient to counteract the intensive oxidative processes in spermatozoa, which eventually resulted in decreased spermatozoa motility. The estimation of antioxidative and OS variables in seminal plasma and spermatozoa may have practical value for the assessment of bull semen quality.

Synthesis and coordination chemistry of TpC*MI complexes where M=Mg, Ca, Sr, Ba and Zn and TpC*=tris[3-(2-methoxy-1,1-dimethyl)pyrazolyl]hydroborate.

PubMed

Chisholm, Malcolm H; Gallucci, Judith C; Yaman, Gulsah

2009-01-14

Reactions involving MI2 where M=Mg, Ca, Sr, Ba or Zn and M'TpC* where M'=Na or Tl and TpC*=tris[3-methoxy-1,1-dimethyl)pyrazolyl]hydroborate in tetrahydrofuran are described leading to the isolation and characterization of the complexes TpC*MgI, , TpC*CaI, , TpC*SrI, , TpC*SrI(THF), , TpC*BaI, , TpC*BaI(pz*H), , where pz*H=3-(2-methoxyl-1,1-dimethyl)pyrazole, TpC*BaI.1/2toluene, and TpC*ZnI, . The compounds , , , , and have been characterized by single-crystal X-ray crystallography. Compounds and are isostructural and are salt-like containing kappa6-TpM+ cations and I- anions. In all other structures, the iodide is bound to the metal and TpC* is kappa6 bonded to the group 2 M(2+) ions. Reactions involving TpC*CaI, , and sodium or lithium alkoxides or amides failed to yield the amide or alkoxide calcium TpC* derivative, though related reactions involving TpC*ZnI, , and KOSiMe3 proceeded quantitatively to yield kappa3TpC*ZnOSiMe3, , which was also structurally characterized and shown to have the kappa3-TpC* bound ligand.

An Investigation of the Relationship Between Readiness Test Scores for Kindergarten Children and Achievement Scores Obtained at the End of Grades One and Two. S.S.T.A. Research Centre Report No. 62.

ERIC Educational Resources Information Center

Warkentin, Lena

The primary purpose of this study was to investigate the relationship between Metropolitan Readiness Test (MRT) scores in kindergarten (MRTK) and grade one (MRT1) with the reading scores of the Canadian Tests of Basic Skills (CTBS) at the end of grades one (CTBSR1) and two (CTBSR2). A secondary purpose of the study was to determine whether the…

Evaluation of Tp-E Interval and Tp-E/QT Ratio in Patients with Aortic Stenosis.

PubMed

Yayla, Çağrı; Bilgin, Murat; Akboğa, Mehmet Kadri; Gayretli Yayla, Kadriye; Canpolat, Uğur; Dinç Asarcikli, Lale; Doğan, Mehmet; Turak, Osman; Çay, Serkan; Özeke, Özcan; Akyel, Ahmet; Yeter, Ekrem; Aydoğdu, Sinan

2016-05-01

The risk of syncope and sudden cardiac death due to ventricular arrhythmias increased in patients with aortic stenosis (AS). Recently, it was shown that Tp-e interval, Tp-e/QT, and Tp-e/QTc ratio can be novel indicators for prediction of ventricular arrhythmias and mortality. We aimed to investigate the association between AS and ventricular repolarization using Tp-e interval and Tp-e/QT ratio. Totally, 105 patients with AS and 60 control subjects were enrolled to this study. The severity of AS was defined by transthoracic echocardiographic examination. Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were measured from the 12-lead electrocardiogram. Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were significantly increased in parallel to the severity of AS (P < 0.001, P = 0.001, and P = 0.001, respectively). Also, it was shown that Tp-e/QTc ratio had significant positive correlation with mean aortic gradient (r = 0.192, P = 0.049). In multivariate logistic regression analysis, Tp-e/QTc ratio and left ventricular mass were found to be independent predictors of severe AS (P = 0.03 and P = 0.04, respectively). Our study showed that Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were increased in patients with severe AS. Tp-e/QTc ratio and left ventricular mass were found as independent predictors of severe AS. © 2015 Wiley Periodicals, Inc.

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

Rycyna, R.E.; Wallace, J.C.; Sharma, M.

Acetone-photosensitized UV irradiation of three thymine oligomers, d(TpT), d(TpTpT), and d(TpTpTpT), forms predominantly cis-syn cyclobutyl photodimers. C-18 reverse-phase high-performance liquid chromatography is used to purify the following positional isomers: d(TpT(p)T), d(T(p)TpT), d-(TpTpT(p)T), d(TpT(p)TpT), d(T(p)TpTpT), and d(T(p)TpT(p)T), where T(p)T represents the cis-syn photodimer. Conformational properties of the cis-syn dimers and adjacent thymine nucleotides have been investigated in solution by using /sup 1/H, /sup 13/C, and /sup 31/P NMR spectroscopy. These studies show that (1) the photodimer conformation in longer oligothymidylates is similar to that in the dinucleoside monophosphate and (2) the cis-syn dimer induces alterations to a greater degree on themore » 5' side than on the 3' side of the photodimer. Specifically, the photodimer distorts the exocyclic bonds epsilon (C3'-O3') in Tp- and ..gamma..(C5'-C4') in -pT(p)- on the 5' side and slightly alters the furanose equilibrium of the -pT nucleotide on the 3' side of the dimer.« less

Pharmacokinetics and tissue distribution study in mice of triptolide-loaded lipid emulsion and accumulation effect on pancreas.

PubMed

Li, Xue; Mao, Yuling; Li, Kai; Shi, Tianyu; Yao, Huimin; Yao, Jianhua; Wang, Shujun

2016-05-01

Triptolide (TP) shows strong anti-tumor activities on various cancer cells, especially on pancreatic cancer. TP inhibits HSP70 expression leading to cell death in pancreatic cancer cells and induces cell death by apoptotic and autophagic pathways. In order to increase the therapeutic index of TP, a novel intravenous TP-loaded delivery system, TP-loaded lipid emulsion (TP-LE), has been developed to treat solid tumor. In the present study, the preparation and characterization of TP-LE were described. The pharmacokinetics and tissue distribution study of TP-LE in mice were also evaluated. Results demonstrated that TP-LE had an average particle size of 154.6 nm, entrapment efficiency (EE%) of 87%, zeta potential of -0.903 mV and autoclaved stability. The pharmacokinetic study showed that blood concentrations of both TP-LE and TP reached a maximum at the end of intravenous administration (1.25 mg/kg) and declined rapidly within the first 10 min with a mean residence time (MRT) of about 10 min. In the tissue distribution study, a preferential accumulation and longer residence time of drug in pancreas were found in TP-LE. The AUC0-60min of TP-LE in pancreas was 2.19 times in comparison to free TP, suggesting that the use of TP-LE conferred improvements in biodistribution, accumulation and therapeutic efficacy in pancreas. Moreover, the concentrations of TP-LE in heart, lung and kidney were lower than that of the TP group, indicating the potential for reduced toxicity of TP-LE. Together, all the results show that TP-LE appears to be a promising formulation for using TP in treating cancer, and more specifically pancreatic cancer.

Flow Characterization Studies of the 10-MW TP3 Arc-Jet Facility: Probe Sweeps

NASA Technical Reports Server (NTRS)

Goekcen, Tahir; Alunni, Antonella I.

2016-01-01

This paper reports computational simulations and analysis in support of calibration and flow characterization tests in a high enthalpy arc-jet facility at NASA Ames Research Center. These tests were conducted in the NASA Ames 10-MW TP3 facility using flat-faced stagnation calorimeters at six conditions corresponding to the steps of a simulated flight heating profile. Data were obtained using a conical nozzle test configuration in which the models were placed in a free jet downstream of the nozzle. Experimental surveys of arc-jet test flow with pitot pressure and heat flux probes were also performed at these arc-heater conditions, providing assessment of the flow uniformity and valuable data for the flow characterization. Two different sets of pitot pressure and heat probes were used: 9.1-mm sphere-cone probes (nose radius of 4.57 mm or 0.18 in) with null-point heat flux gages, and 15.9-mm (0.625 in) diameter hemisphere probes with Gardon gages. The probe survey data clearly show that the test flow in the TP3 facility is not uniform at most conditions (not even axisymmetric at some conditions), and the extent of non-uniformity is highly dependent on various arc-jet parameters such as arc current, mass flow rate, and the amount of cold-gas injection at the arc-heater plenum. The present analysis comprises computational fluid dynamics simulations of the nonequilibrium flowfield in the facility nozzle and test box, including the models tested. Comparisons of computations with the experimental measurements show reasonably good agreement except at the extreme low pressure conditions of the facility envelope.

Late Holocene vegetation and climate change on the southeastern Tibetan Plateau: Implications for the Indian Summer Monsoon and links to the Indian Ocean Dipole

NASA Astrophysics Data System (ADS)

Li, Kai; Liu, Xingqi; Wang, Yongbo; Herzschuh, Ulrike; Ni, Jian; Liao, Mengna; Xiao, Xiayun

2017-12-01

The Indian Summer Monsoon (ISM) is one of the most important climate systems, whose variability and driving mechanisms are of broad interest for academic and societal communities. Here, we present a well-dated high-resolution pollen analysis from a 4.82-m long sediment core taken from Basomtso, in the southeastern Tibetan Plateau (TP), which depicts the regional climate changes of the past millennium. Our results show that subalpine coniferous forest was dominant around Basomtso from ca. 867 to ca. 750 cal. yr BP, indicating a warm and semi-humid climate. The timberline in the study area significantly decreased from ca. 750 to ca. 100 cal. yr BP, and a cold climate, corresponding to the Little Ice Age (LIA) prevailed. Since ca. 100 cal. yr BP, the vegetation type changed to forest-meadow with rising temperatures and moisture. Ordination analysis reveals that the migration of vegetation was dominated by regional temperatures and then by moisture. Further comparisons between the Basomtso pollen record and the regional temperature reconstructions underscore the relevance of the Basomtso record from the southeastern TP for regional and global climatologies. Our pollen based moisture reconstruction demonstrates the strong multicentennial-scale link to ISM variability, providing solid evidence for the increase of monsoonal strengths over the past four centuries. Spectral analysis indicates the potential influence of solar forcing. However, a closer relationship has been observed between multicentennial ISM variations and Indian Ocean sea surface temperature anomalies (SSTs), suggesting that the variations in monsoonal precipitation over the southeastern TP are probably driven by the Indian Ocean Dipole on the multicentennial scale.

Spring Soil Temperature Anomalies over Tibetan Plateau and Summer Droughts/Floods in East Asia

NASA Astrophysics Data System (ADS)

Xue, Y.; Li, W.; LI, Q.; Diallo, I.; Chu, P. C.; Guo, W.; Fu, C.

2017-12-01

Recurrent extreme climate events, such as droughts and floods, are important features of the climate of East Asia, especially over the Yangtze River basin. Many studies have attributed these episodes to variability and anomaly of global sea surface temperatures (SST) anomaly. In addition, snow in the Tibetan Plateau has also been considered as one of the factors affecting the Asian monsoon variability. However, studies have consistently shown that SST along is unable to explain the extreme climate events fully and snow has difficulty to use as a predictor. Remote effects of observed large-scale land surface temperature (LST) and subsurface temperature variability in Tibetan Plateau (TP) on East Asian regional droughts/floods, however, have been largely ignored. We conjecture that a temporally filtered response to snow anomalies may be preserved in the LST anomaly. In this study, evidence from climate observations and model simulations addresses the LST/SUBT effects. The Maximum Covariance Analysis (MCA) of observational data identifies that a pronounce spring LST anomaly pattern over TP is closely associated with precipitation anomalies in East Asia with a dipole pattern, i.e., negative/positive TP spring LST anomaly is associated with the summer drought/flood over the region south of the Yangtze River and wet/dry conditions to the north of the Yangtze River. Climate models were used to demonstrate a causal relationship between spring cold LST anomaly in the TP and the severe 2003 drought over the southern part of the Yangtze River in eastern Asia. This severe drought resulted in 100 x 106 kg crop yield losses and an economic loss of 5.8 billion Chinese Yuan. The modeling study suggests that the LST effect produced about 58% of observed precipitation deficit; while the SST effect produced about 32% of the drought conditions. Meanwhile, the LST and SST effects also simulated the observed flood over to the north of the Yangtze River. This suggests that inclusion of this LST effect is essential to make reliable East Asian drought/flood predictions.

Definite Project Report for Section 205 Flood Control, Illinois River, Liverpool, Illinois, with Final Environmental Impact Statement

DTIC Science & Technology

1989-10-01

consisting of fat clay, sandy lean clay, and clayey sand. 7 Climate The climate of Fulton County is humid continental and is characterized by cold...Tp a. FAT Can U0I S go in on &- WI - WU. GAJm. In.~a Ts IPA a 0.2 ft 17. AW’U.Z I 9 £1 t som alsieIpm n lawe W. . MY4 CIA am a s V 0 WMO a~~~a ". MVU...feet of Cahokia alluvium. The alluvium is made up of 5 feet of fat clay overlying 4 feet of sandy lean clay. Indicated in situ shear strengths range

Genome-wide characterization reveals complex interplay between TP53 and TP63 in response to genotoxic stress

PubMed Central

McDade, Simon S.; Patel, Daksha; Moran, Michael; Campbell, James; Fenwick, Kerry; Kozarewa, Iwanka; Orr, Nicholas J.; Lord, Christopher J.; Ashworth, Alan A.; McCance, Dennis J.

2014-01-01

In response to genotoxic stress the TP53 tumour suppressor activates target gene expression to induce cell cycle arrest or apoptosis depending on the extent of DNA damage. These canonical activities can be repressed by TP63 in normal stratifying epithelia to maintain proliferative capacity or drive proliferation of squamous cell carcinomas, where TP63 is frequently overexpressed/amplified. Here we use ChIP-sequencing, integrated with microarray analysis, to define the genome-wide interplay between TP53 and TP63 in response to genotoxic stress in normal cells. We reveal that TP53 and TP63 bind to overlapping, but distinct cistromes of sites through utilization of distinctive consensus motifs and that TP53 is constitutively bound to a number of sites. We demonstrate that cisplatin and adriamycin elicit distinct effects on TP53 and TP63 binding events, through which TP53 can induce or repress transcription of an extensive network of genes by direct binding and/or modulation of TP63 activity. Collectively, this results in a global TP53-dependent repression of cell cycle progression, mitosis and DNA damage repair concomitant with activation of anti-proliferative and pro-apoptotic canonical target genes. Further analyses reveal that in the absence of genotoxic stress TP63 plays an important role in maintaining expression of DNA repair genes, loss of which results in defective repair. PMID:24823795

Forecasting ENSO events: A neural network-extended EOF approach

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

Tangang, F.T.; Tang, B.; Monahan, A.H.

The authors constructed neural network models to forecast the sea surface temperature anomalies (SSTA) for three regions: Nino 4. Nino 3.5, and Nino 3, representing the western-central, the central, and the eastern-central parts of the equatorial Pacific Ocean, respectively. The inputs were the extended empirical orthogonal functions (EEOF) of the sea level pressure (SLP) field that covered the tropical Indian and Pacific Oceans and evolved for a duration of 1 yr. The EEOFs greatly reduced the size of the neural networks from those of the authors` earlier papers using EOFs. The Nino 4 region appeared to be the best forecastedmore » region, with useful skills up to a year lead time for the 1982-93 forecast period. By network pruning analysis and spectral analysis, four important inputs were identified: modes 1, 2, and 6 of the SLP EEOFs and the SSTA persistence. Mode 1 characterized the low-frequency oscillation (LFO, with 4-5-yr period), and was seen as the typical ENSO signal, while mode 2, with a period of 2-5 yr, characterized the quasi-biennial oscillation (QBO) plus the LFO. Mode 6 was dominated by decadal and interdecadal variations. Thus, forecasting ENSO required information from the QBO, and the decadal-interdecadal oscillations. The nonlinearity of the networks tended to increase with lead time and to become stronger for the eastern regions of the equatorial Pacific Ocean. 35 refs., 14 figs., 4 tabs.« less

Physical forcing of late summer chlorophyll a blooms in the oligotrophic eastern North Pacific

NASA Astrophysics Data System (ADS)

Toyoda, Takahiro; Okamoto, Suguru

2017-03-01

We investigated physical forcing of late summer chlorophyll a (chl a) blooms in the oligotrophic eastern North Pacific Ocean by using ocean reanalysis and satellite data. Relatively large chl a blooms as defined in this study occurred in August-October following sea surface temperature (SST) anomaly (SSTA) decreases, mixed layer deepening, and temperature and salinity increases at the bottom of the mixed layer. These physical conditions were apparently induced by the entrainment of subsurface water resulting from the destabilization of the surface layer caused by anomalous northward Ekman transport of subtropical waters of higher salinity. Salinity-normalized total alkalinity data provide supporting evidence for nutrient supply by the entrainment process. We next investigated the impact of including information about the entrainment on bloom identification. The results of analyses using reanalysis data and of those using only satellite data showed large SSTA decreases when the northward Ekman salinity transports were large, implying that the entrainment of subsurface water is well represented in both types of data. After surface-destabilizing conditions were established, relatively high surface chl a concentrations were observed. The use of SST information can further improve the detection of high chl a concentrations. Although the detection of high chl a concentrations would be enhanced by finer data resolution and the inclusion of biogeochemical parameters in the ocean reanalysis, our results obtained by using existing reanalysis data as well as recent satellite data are valuable for better understanding and prediction of lower trophic ecosystem variability.

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

Weber, Thomas J.; Markillie, Lye MENG.

The thromboxane A{sub 2} (TXA{sub 2}) receptor (TP) is represented by two alternatively spliced forms, termed the platelet/placental (TP-P) and endothelial (TP-E) type receptors. Experimental evidence suggests that TP isoforms may be regulated by novel ligands termed the isoprostanes, which paradoxically act as TP agonists in smooth muscle and TP antagonists in platelet preparations. Here we have investigated whether prototypical isoprostanes (8-iso-PG{sub 2{sub {alpha}}} and 8-iso-PGE{sub 2}) regulate the activity of TP isoforms expressed in Chinese Hamster Ovary (CHO) cells using activator protein-1 (AP-1)-luciferase activity as a reporter. AP-1-luciferase activity was increased by a TP agonist (U46619) in CHO cellsmore » transfected with the human TP-P and TP-E receptors and this response was fully inhibited by TP antagonists (ISAP, SQ29,548). AP-1-luciferase activity was potently (nM) increased by 8-iso-PGE2 in CHO TP-P and TP-E cells, and this response was partially inhibited by cotreatment of cells with TP antagonists, while 8-iso-PGF{sub 2{sub {alpha}}} was without effect. Cyclooxygenase inhibitors did not abolish 8-iso-PGE{sub 2} mediated AP-1-luciferase activity, indicating that this response is not dependent on de novo TXA2 biosynthesis. Interestingly, 8-iso-PGE{sub 2}-mediated AP-1-luciferase activity was near maximal in naive cells between 1-10 nM concentrations, and this response was not inhibited by TP antagonist or reproduced by agonists for TP or EP1/EP3 receptors. These observations (1) support a role for novel ligands in the regulation of TP-dependent signaling, (2) indicate that TP-P and TP-E couple to AP-1, (3) provide further evidence that isoprostanes function as TP agonists in a cell-type specific fashion, and (4) indicate that additional targets regulated by 8-iso-PGE{sub 2} couple to AP-1.« less

Enhanced immune response and protective efficacy of a Treponema pallidum Tp92 DNA vaccine vectored by chitosan nanoparticles and adjuvanted with IL-2.

PubMed

Zhao, Feijun; Wu, Yimou; Zhang, Xiaohong; Yu, Jian; Gu, Weiming; Liu, Shuangquan; Zeng, Tiebing; Zhang, Yuejun; Wang, Shiping

2011-10-01

In this study, the immune-modulatory and protective efficacy of using an interleukin-2 (IL-2) expression plasmid as a genetic adjuvant and chitosan (CS) nanoparticles as vectors to enhance a Tp92 DNA vaccine candidate were investigated in a Treponema pallidum (Tp) rabbit challenge model. CS vectoring of pTp92 or pIL-2 were both demonstrated to augment anti-Tp92 antibody levels induced by pTp92 DNA vaccines. Interestingly, the combination of CS vectored Tp92 and pIL-2 led to the greatest enhancements of anti-Tp92 antibodies and T-cell proliferation (p < 0.05). At week 10 after the first immunization, 15 of the 18 rabbits in each group were challenged with Tp Nichols strain and monitored for skin lesions and ulcer lesions. Ratios of positive skin lesions and ratios of ulcer lesions in groups immunized with pTp92 were significantly lower than those of the empty vector or PBS groups (p < 0.05), demonstrating that pTp92 immunization elicited significant protective efficacy against the Tp Nichols strain challenge. CS vectored and pIL-2 adjuvanted pTp92 immunized animals exhibited the lowest rates of positive skin and ulcer lesions. Male New Zealand white rabbits were randomly assigned to groups (n = 18/group) and immunized intramuscularly with pTp92 based plasmid DNA constructs (100 μg of DNA/rabbit/immunization). Two weeks before Tp challenge (Week 8), three rabbits from each group were used to determine cytokine measurements and fifteen rabbits from each group were used for Tp challenge studies. Intramuscular injection of pTp92 induced strong humoral and cellular immune responses and conferred protection from Tp challenge in rabbits. The use of CS as a pTp92 vector or pIL-2 as an adjuvant achieved a superior level of protective efficacy against Tp challenge, however CS vectored, IL-2 adjuvanted pTp92 immunization conferred the highest level of protective efficacy.

Theileria parva antigens recognized by CD8+ T cells show varying degrees of diversity in buffalo-derived infected cell lines.

PubMed

Sitt, Tatjana; Pelle, Roger; Chepkwony, Maurine; Morrison, W Ivan; Toye, Philip

2018-05-06

The extent of sequence diversity among the genes encoding 10 antigens (Tp1-10) known to be recognized by CD8+ T lymphocytes from cattle immune to Theileria parva was analysed. The sequences were derived from parasites in 23 buffalo-derived cell lines, three cattle-derived isolates and one cloned cell line obtained from a buffalo-derived stabilate. The results revealed substantial variation among the antigens through sequence diversity. The greatest nucleotide and amino acid diversity were observed in Tp1, Tp2 and Tp9. Tp5 and Tp7 showed the least amount of allelic diversity, and Tp5, Tp6 and Tp7 had the lowest levels of protein diversity. Tp6 was the most conserved protein; only a single non-synonymous substitution was found in all obtained sequences. The ratio of non-synonymous: synonymous substitutions varied from 0.84 (Tp1) to 0.04 (Tp6). Apart from Tp2 and Tp9, we observed no variation in the other defined CD8+ T cell epitopes (Tp4, 5, 7 and 8), indicating that epitope variation is not a universal feature of T. parva antigens. In addition to providing markers that can be used to examine the diversity in T. parva populations, the results highlight the potential for using conserved antigens to develop vaccines that provide broad protection against T. parva.

Rapid formation and pollutant removal ability of aerobic granules in a sequencing batch airlift reactor at low temperature.

PubMed

Jiang, Yu; Shang, Yu; Wang, Hongyu; Yang, Kai

2016-12-01

The start-up of an aerobic granular sludge (AGS) reactor at low temperature was more difficult than at ambient temperature.The rapid formation and characteristics of AGS in a sequencing batch airlift reactor at low temperature were investigated. The nutrient removal ability of the system was also evaluated. It was found that compact granules with clear boundary were formed within 10 days and steady state was achieved within 25 days. The settling properties of sludge were improved with the increasing secretion of extracellular polymeric substances and removal performances of pollutants were enhanced along with granulation. The average removal efficiencies of COD, NH4(+)-N, total nitrogen (TN), total phosphorus (TP) after aerobic granules maturing were over 90.9%, 94.7%, 75.4%, 80.2%, respectively. The rise of temperature had little impact on pollutant biodegradation while the variation of dissolved oxygen caused obvious changes in TN and TP removal rates. COD concentrations of effluents were below 30 mg l(-1) in most cycles of operation with a wide range of organic loading rates (0.6-3.0 kg COD m(-3) d(-1)). The rapid granulation and good performance of pollutant reduction by the system might provide an alternate for wastewater treatment in cold regions.

Hypoxia increases pulmonary arterial thromboxane receptor internalization independent of receptor sensitization.

PubMed

Fediuk, J; Sikarwar, A S; Lizotte, P P; Hinton, M; Nolette, N; Dakshinamurti, S

2015-02-01

Persistent Pulmonary Hypertension of the Newborn (PPHN) is characterized by sustained vasospasm and an increased thromboxane:prostacyclin ratio. Thromboxane (TP) receptors signal via Gαq to mobilize IP3 and Ca(2+), causing pulmonary arterial constriction. We have previously reported increased TP internalization in hypoxic pulmonary arterial (PA) myocytes. Serum-deprived PA myocytes were grown in normoxia (NM) or hypoxia (HM) for 72 h. TP localization was visualized in agonist-naïve and -challenged NM and HM by immunocytochemistry. Pathways for agonist-induced TP receptor internalization were determined by inhibiting caveolin- or clathrin-mediated endocytosis, and caveolar fractionation. Roles of actin and tubulin in TP receptor internalization were assessed using inhibitors of tubulin, actin-stabilizing or -destabilizing agents. PKA, PKC or GRK activation and inhibition were used to determine the kinase responsible for post-agonist receptor internalization. Agonist-naïve HM had decreased cell surface TP, and greater TP internalization after agonist challenge. TP protein did not sort with caveolin-rich fractions. Inhibition of clathrin prevented TP internalization. Both actin-stabilizing and -destabilizing agents prevented TP endocytosis in NM, while normalizing TP internalization in HM. Velocity of TP internalization was unaffected by PKA activity, but PKC activation normalized TP receptor internalization in HM. GRK inhibition had no effect. We conclude that in hypoxic myocytes, TP is internalized faster and to a greater extent than in normoxic controls. Internalization of the agonist-challenged TP requires clathrin, dynamic actin and is sensitive to PKC activity. TP receptor trafficking and signaling in hypoxia are pivotal to understanding increased vasoconstrictor sensitivity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Milrinone attenuates thromboxane receptor-mediated hyperresponsiveness in hypoxic pulmonary arterial myocytes

PubMed Central

Santhosh, KT; Elkhateeb, O; Nolette, N; Outbih, O; Halayko, AJ; Dakshinamurti, S

2011-01-01

BACKGROUND AND PURPOSE Neonatal pulmonary hypertension (PPHN) is characterized by pulmonary vasoconstriction, due in part to dysregulation of the thromboxane prostanoid (TP) receptor. Hypoxia induces TP receptor–mediated hyperresponsiveness, whereas serine phosphorylation mediates desensitization of TP receptors. We hypothesized that prostacyclin (IP) receptor activity induces TP receptor phosphorylation and decreases ligand affinity; that TP receptor sensitization in hypoxic myocytes is due to IP receptor inactivation; and that this would be reversible by the cAMP-specific phosphodiesterase inhibitor milrinone. EXPERIMENTAL APPROACH We examined functional regulation of TP receptors by serine phosphorylation and effects of IP receptor stimulation and protein kinase A (PKA) activity on TP receptor sensitivity in myocytes from neonatal porcine resistance pulmonary arteries after 72 h hypoxia in vitro. Ca2+ response curves to U46619 (TP receptor agonist) were determined in hypoxic and normoxic myocytes incubated with or without iloprost (IP receptor agonist), forskolin (adenylyl cyclase activator), H8 (PKA inhibitor) or milrinone. TP and IP receptor saturation binding kinetics were measured in presence of iloprost or 8-bromo-cAMP. KEY RESULTS Ligand affinity for TP receptors was normalized in vitro by IP receptor signalling intermediates. However, IP receptor affinity was compromised in hypoxic myocytes, decreasing cAMP production. Milrinone normalized TP receptor sensitivity in hypoxic myocytes by restoring PKA-mediated regulatory TP receptor phosphorylation. CONCLUSIONS AND IMPLICATIONS TP receptor sensitivity and EC50 for TP receptor agonists was regulated by PKA, as TP receptor serine phosphorylation by PKA down-regulated Ca2+ mobilization. Hypoxia decreased IP receptor activity and cAMP generation, inducing TP receptor hyperresponsiveness, which was reversed by milrinone. PMID:21385177

Prolonged Tp-e Interval in Down Syndrome Patients with Congenitally Normal Hearts.

PubMed

Kucuk, Mehmet; Karadeniz, Cem; Ozdemir, Rahmi; Meşe, Timur

2018-03-25

Heterogeneity of ventricular repolarization has been assessed by using the QT dispersion in Down syndrome (DS) patients with congenitally normal hearts. However, novel repolarization indexes, the Tp-e interval and Tp-e/QT ratio, have not previously been evaluated in these patients. The aim of this study was to evaluate the Tp-e interval and Tp-e/QT ratio in DS patients without congenital heart defects. Twelve-lead surface electrocardiograms of 160 DS patients and 110 age- and sex-matched healthy controls were used to evaluate and compare the Tp-e interval, Tp-e dispersion, and Tp-e/QT ratio. Heart rate, Tp-e interval, Tp-e dispersion, Tp-e/QT and Tp-e/QTc ratios were significantly higher in DS group than in the controls. Myocardial repolarization indexes in DS patients with congenitally normal hearts were found to be prolonged compared to those in normal controls. Further evaluation is warranted to reveal a relationship between prolonged repolarization indexes and arrhythmic events in these patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

TP53 mutations, expression and interaction networks in human cancers

PubMed Central

Wang, Xiaosheng; Sun, Qingrong

2017-01-01

Although the associations of p53 dysfunction, p53 interaction networks and oncogenesis have been widely explored, a systematic analysis of TP53 mutations and its related interaction networks in various types of human cancers is lacking. Our study explored the associations of TP53 mutations, gene expression, clinical outcomes, and TP53 interaction networks across 33 cancer types using data from The Cancer Genome Atlas (TCGA). We show that TP53 is the most frequently mutated gene in a number of cancers, and its mutations appear to be early events in cancer initiation. We identified genes potentially repressed by p53, and genes whose expression correlates significantly with TP53 expression. These gene products may be especially important nodes in p53 interaction networks in human cancers. This study shows that while TP53-truncating mutations often result in decreased TP53 expression, other non-truncating TP53 mutations result in increased TP53 expression in some cancers. Survival analyses in a number of cancers show that patients with TP53 mutations are more likely to have worse prognoses than TP53-wildtype patients, and that elevated TP53 expression often leads to poor clinical outcomes. We identified a set of candidate synthetic lethal (SL) genes for TP53, and validated some of these SL interactions using data from the Cancer Cell Line Project. These predicted SL genes are promising candidates for experimental validation and the development of personalized therapeutics for patients with TP53-mutated cancers. PMID:27880943

TP53 mutations, expression and interaction networks in human cancers.

PubMed

Wang, Xiaosheng; Sun, Qingrong

2017-01-03

Although the associations of p53 dysfunction, p53 interaction networks and oncogenesis have been widely explored, a systematic analysis of TP53 mutations and its related interaction networks in various types of human cancers is lacking. Our study explored the associations of TP53 mutations, gene expression, clinical outcomes, and TP53 interaction networks across 33 cancer types using data from The Cancer Genome Atlas (TCGA). We show that TP53 is the most frequently mutated gene in a number of cancers, and its mutations appear to be early events in cancer initiation. We identified genes potentially repressed by p53, and genes whose expression correlates significantly with TP53 expression. These gene products may be especially important nodes in p53 interaction networks in human cancers. This study shows that while TP53-truncating mutations often result in decreased TP53 expression, other non-truncating TP53 mutations result in increased TP53 expression in some cancers. Survival analyses in a number of cancers show that patients with TP53 mutations are more likely to have worse prognoses than TP53-wildtype patients, and that elevated TP53 expression often leads to poor clinical outcomes. We identified a set of candidate synthetic lethal (SL) genes for TP53, and validated some of these SL interactions using data from the Cancer Cell Line Project. These predicted SL genes are promising candidates for experimental validation and the development of personalized therapeutics for patients with TP53-mutated cancers.

The Golgi localization of phosphatidylinositol transfer protein beta requires the protein kinase C-dependent phosphorylation of serine 262 and is essential for maintaining plasma membrane sphingomyelin levels.

PubMed

van Tiel, Claudia M; Westerman, Jan; Paasman, Marten A; Hoebens, Martha M; Wirtz, Karel W A; Snoek, Gerry T

2002-06-21

Recombinant mouse phosphatidylinositol transfer protein (PI-TP)beta is a substrate for protein kinase C (PKC)-dependent phosphorylation in vitro. Based on site-directed mutagenesis and two-dimensional tryptic peptide mapping, Ser(262) was identified as the major site of phosphorylation and Ser(165) as a minor phosphorylation site. The phospholipid transfer activities of wild-type PI-TP beta and PI-TP beta(S262A) were identical, whereas PI-TP beta(S165A) was completely inactive. PKC-dependent phosphorylation of Ser(262) also had no effect on the transfer activity of PI-TP beta. To investigate the role of Ser(262) in the functioning of PI-TP beta, wtPI-TP beta and PI-TP beta(S262A) were overexpressed in NIH3T3 fibroblast cells. Two-dimensional PAGE analysis of cell lysates was used to separate PI-TP beta from its phosphorylated form. After Western blotting, wtPI-TP beta was found to be 85% phosphorylated, whereas PI-TP beta(S262A) was not phosphorylated. In the presence of the PKC inhibitor GF 109203X, the phosphorylated form of wtPI-TP beta was strongly reduced. Immunolocalization showed that wtPI-TP beta was predominantly associated with the Golgi membranes. In the presence of the PKC inhibitor, wtPI-TP beta was distributed throughout the cell similar to what was observed for PI-TP beta(S262A). In contrast to wtPI-TP beta overexpressors, cells overexpressing PI-TP beta(S262A) were unable to rapidly replenish sphingomyelin in the plasma membrane upon degradation by sphingomyelinase. This implies that PKC-dependent association with the Golgi complex is a prerequisite for PI-TP beta to express its effect on sphingomyelin metabolism.

Nutlin‐3a selects for cells harbouring TP 53 mutations

PubMed Central

Hollstein, Monica; Arlt, Volker M.; Phillips, David H.

2016-01-01

TP53 mutations occur in half of all human tumours. Mutagen‐induced or spontaneous TP53 mutagenesis can be studied in vitro using the human TP53 knock‐in (Hupki) mouse embryo fibroblast (HUF) immortalisation assay (HIMA). TP53 mutations arise in up to 30% of mutagen‐treated, immortalised HUFs; however, mutants are not identified until TP53 sequence analysis following immortalisation (2–5 months) and much effort is expended maintaining TP53‐WT cultures. In order to improve the selectivity of the HIMA for HUFs harbouring TP53 mutations, we explored the use of Nutlin‐3a, an MDM2 inhibitor that leads to stabilisation and activation of wild‐type (WT) p53. First, we treated previously established immortal HUF lines carrying WT or mutated TP53 with Nutlin‐3a to examine the effect on cell growth and p53 activation. Nutlin‐3a induced the p53 pathway in TP53‐WT HUFs and inhibited cell growth, whereas most TP53‐mutated HUFs were resistant to Nutlin‐3a. We then assessed whether Nutlin‐3a treatment could discriminate between TP53‐WT and TP53‐mutated cells during the HIMA (n = 72 cultures). As immortal clones emerged from senescent cultures, each was treated with 10 µM Nutlin‐3a for 5 days and observed for sensitivity or resistance. TP53 was subsequently sequenced from all immortalised clones. We found that all Nutlin‐3a‐resistant clones harboured TP53 mutations, which were diverse in position and functional impact, while all but one of the Nutlin‐3a‐sensitive clones were TP53‐WT. These data suggest that including a Nutlin‐3a counter‐screen significantly improves the specificity and efficiency of the HIMA, whereby TP53‐mutated clones are selected prior to sequencing and TP53‐WT clones can be discarded. PMID:27813088

Milrinone attenuates thromboxane receptor-mediated hyperresponsiveness in hypoxic pulmonary arterial myocytes.

PubMed

Santhosh, K T; Elkhateeb, O; Nolette, N; Outbih, O; Halayko, A J; Dakshinamurti, S

2011-07-01

Neonatal pulmonary hypertension (PPHN) is characterized by pulmonary vasoconstriction, due in part to dysregulation of the thromboxane prostanoid (TP) receptor. Hypoxia induces TP receptor-mediated hyperresponsiveness, whereas serine phosphorylation mediates desensitization of TP receptors. We hypothesized that prostacyclin (IP) receptor activity induces TP receptor phosphorylation and decreases ligand affinity; that TP receptor sensitization in hypoxic myocytes is due to IP receptor inactivation; and that this would be reversible by the cAMP-specific phosphodiesterase inhibitor milrinone. We examined functional regulation of TP receptors by serine phosphorylation and effects of IP receptor stimulation and protein kinase A (PKA) activity on TP receptor sensitivity in myocytes from neonatal porcine resistance pulmonary arteries after 72 h hypoxia in vitro. Ca(2+) response curves to U46619 (TP receptor agonist) were determined in hypoxic and normoxic myocytes incubated with or without iloprost (IP receptor agonist), forskolin (adenylyl cyclase activator), H8 (PKA inhibitor) or milrinone. TP and IP receptor saturation binding kinetics were measured in presence of iloprost or 8-bromo-cAMP. Ligand affinity for TP receptors was normalized in vitro by IP receptor signalling intermediates. However, IP receptor affinity was compromised in hypoxic myocytes, decreasing cAMP production. Milrinone normalized TP receptor sensitivity in hypoxic myocytes by restoring PKA-mediated regulatory TP receptor phosphorylation. TP receptor sensitivity and EC(50) for TP receptor agonists was regulated by PKA, as TP receptor serine phosphorylation by PKA down-regulated Ca(2+) mobilization. Hypoxia decreased IP receptor activity and cAMP generation, inducing TP receptor hyperresponsiveness, which was reversed by milrinone. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Tp-e Interval, Tp-e/QTc Ratio, and Fragmented QRS Are Correlated with the Severity of Liver Cirrhosis.

PubMed

Akboga, Mehmet Kadri; Yuksel, Mahmut; Balci, Kevser Gulcihan; Kaplan, Mustafa; Cay, Serkan; Gokbulut, Volkan; Yayla, Cagri; Ertem, Ahmet Goktug; Ayhan, Meral Akdogan; Topaloglu, Serkan; Aras, Dursun

2017-01-01

Arrhythmias and electrocardiographic changes are reported in several noncardiac diseases, including liver cirrhosis (LC). We intended to evaluate the interval from the peak to the end of the electrocardiographic T wave (Tp-e), Tp-e/QTc ratio, and fQRS as presumed markers of arrhythmias in LC. In this cross-sectional study, a total of 88 consecutive patients with LC according to clinical, biological, ultrasonographic, or histological criteria and 73 control subjects were enrolled. The severity of cirrhosis was classified according to Pugh-Child's classification and Model for End-Stage Liver Disease (MELD) score. Tp-e interval, Tp-e/QTc ratio, and fQRS rates were measured from the 12-lead electrocardiogram. Tp-e interval, Tp-e/QTc ratio and fQRS rates were significantly increased in parallel to the severity of LC (P < 0.001, P < 0.001, and P = 0.003, respectively). In correlation analysis, Pugh-Child stage showed a significantly positive correlation with Tp-e interval (r = 0.462, P < 0.001), QTc interval (r = 0.373, P < 0.001), Tp-e/QTc ratio (r = 0.352, P < 0.001), and fQRS (r = 0.407, P < 0.001). Furthermore, Tp-e interval (r = 0.414, P < 0.001) and Tp-e/QTc ratio (r = 0.426, P< 0.001) had significant positive correlation with MELD score. Our study demonstrated that Tp-e interval, Tp-e/QTc ratios, and fQRS rates were significantly increased in parallel to the severity of LC. Thus, these findings may implicate that Tp-e interval, Tp-e/QTc ratio, and fQRS may be novel and useful indicators for prediction of arrhythmias in LC. © 2016 Wiley Periodicals, Inc.

Study of the Antimicrobial Activity of Tilapia Piscidin 3 (TP3) and TP4 and Their Effects on Immune Functions in Hybrid Tilapia (Oreochromis spp.)

PubMed Central

Pan, Chieh-Yu; Tsai, Tsung-Yu; Su, Bor-Chyuan; Hui, Cho-Fat; Chen, Jyh-Yih

2017-01-01

To address the growing concern over antibiotic-resistant microbial infections in aquatic animals, we tested several promising alternative agents that have emerged as new drug candidates. Specifically, the tilapia piscidins are a group of peptides that possess antimicrobial, wound-healing, and antitumor functions. In this study, we focused on tilapia piscidin 3 (TP3) and TP4, which are peptides derived from Oreochromis niloticus, and investigated their inhibition of acute bacterial infections by infecting hybrid tilapia (Oreochromis spp.) with Vibrio vulnificus and evaluating the protective effects of pre-treating, co-treating, and post-treating fish with TP3 and TP4. In vivo experiments showed that co-treatment with V. vulnificus and TP3 (20 μg/fish) or TP4 (20 μg/fish) achieved 95.3% and 88.9% survival rates, respectively, after seven days. When we co-injected TP3 or TP4 and V. vulnificus into tilapia and then re-challenged the fish with V. vulnificus after 28 days, the tilapia exhibited survival rates of 35.6% and 42.2%, respectively. Pre-treatment with TP3 (30 μg/fish) or TP4 (20 μg/fish) for 30 minutes prior to V. vulnificus infection resulted in high survival rates of 28.9% and 37.8%, respectively, while post-treatment with TP3 (20 μg/fish or 30 μg/fish) or TP4 (20 μg/fish) 30 minutes after V. vulnificus infection yielded high survival rates of 33.3% and 48.9%. In summary, pre-treating, co-treating, and post-treating fish with TP3 or TP4 all effectively decreased the number of V. vulnificus bacteria and promoted significantly lower mortality rates in tilapia. The minimum inhibitory concentrations (MICs) of TP3 and TP4 that were effective for treating fish infected with V. vulnificus were 7.8 and 62.5 μg/ml, respectively, whereas the MICs of kanamycin and ampicillin were 31.2 and 3.91 μg/ml. The antimicrobial activity of these peptides was confirmed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM), both of which showed that V. vulnificus disrupted the outer membranes of cells, resulting in the loss of cell shape and integrity. We examined whether TP3 and TP4 increased the membrane permeability of V. vulnificus by measuring the fluorescence resulting from the uptake of 1-N-phenyl-naphthylamine (NPN). Treating fish with TP3 and TP4 under different pH and temperature conditions did not significantly increase MIC values, suggesting that temperature and the acid-base environment do not affect AMP function. In addition, the qPCR results showed that TP3 and TP4 influence the expression of immune-responsive genes, including interleukin (IL)-1β, IL-6, and IL-8. In this study, we demonstrate that TP3 and TP4 show potential for development as drugs to combat fish bacterial infections in aquaculture. PMID:28085905

A Valuable Tool in Predicting Poor Outcome due to Sepsis in Pediatric Intensive Care Unit: Tp-e/QT Ratio.

PubMed

Ozdemir, Rahmi; Isguder, Rana; Kucuk, Mehmet; Karadeniz, Cem; Ceylan, Gokhan; Katipoglu, Nagehan; Yilmazer, Murat Muhtar; Yozgat, Yilmaz; Mese, Timur; Agin, Hasan

2016-10-01

To assess the feasibility of 12-lead electrocardiographic (ECG) measures such as P wave dispersion (PWd), QT interval, QT dispersion (QTd), Tp-e interval, Tp-e/QT and Tp-e/QTc ratio in predicting poor outcome in patients diagnosed with sepsis in pediatric intensive care unit (PICU). Ninety-three patients diagnosed with sepsis, severe sepsis or septic shock and 103 age- and sex-matched healthy children were enrolled into the study. PWd, QT interval, QTd, Tp-e interval and Tp-e/QT, Tp-e/QTc ratios were obtained from a 12-lead electrocardiogram. PWd, QTd, Tp-e interval and Tp-e/QT, Tp-e/QTc ratios were significantly higher in septic patients compared with the controls. During the study period, 41 patients had died. In multivariate logistic regression analyses, only Tp-e/QT ratio was found to be an independent predictor of mortality. The ECG measurements can predict the poor outcome in patients with sepsis. The Tp-e/QT ratio may be a valuable tool in predicting mortality for patients with sepsis in the PICU. © The Author [2016]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Glucagon-Secreting Alpha Cell Selective Two-Photon Fluorescent Probe TP-α: For Live Pancreatic Islet Imaging.

PubMed

Agrawalla, Bikram Keshari; Chandran, Yogeswari; Phue, Wut-Hmone; Lee, Sung-Chan; Jeong, Yun-Mi; Wan, Si Yan Diana; Kang, Nam-Young; Chang, Young-Tae

2015-04-29

Two-photon (TP) microscopy has an advantage for live tissue imaging which allows a deeper tissue penetration up to 1 mm comparing to one-photon (OP) microscopy. While there are several OP fluorescence probes in use for pancreatic islet imaging, TP imaging of selective cells in live islet still remains a challenge. Herein, we report the discovery of first TP live pancreatic islet imaging probe; TP-α (Two Photon-alpha) which can selectively stain glucagon secreting alpha cells. Through fluorescent image based screening using three pancreatic cell lines, we discovered TP-α from a TP fluorescent dye library TPG (TP-Green). In vitro fluorescence test showed that TP-α have direct interaction and appear glucagon with a significant fluorescence increase, but not with insulin or other hormones/analytes. Finally, TP-α was successfully applied for 3D imaging of live islets by staining alpha cell directly. The newly developed TP-α can be a practical tool to evaluate and identify live alpha cells in terms of localization, distribution and availability in the intact islets.

Evaluation of Tp-Te Interval and Tp-Te/QT Ratio in Patients with Coronary Slow Flow Tp-Te/QT Ratio and Coronary Slow Flow.

PubMed

Tenekecioglu, Erhan; Karaagac, Kemal; Yontar, Osman Can; Agca, Fahriye Vatansever; Ozluk, Ozlem Arican; Tutuncu, Ahmet; Arslan, Burhan; Yilmaz, Mustafa

2015-06-01

Coronary slow flow (CSF) phenomenon is described by angiographically normal coronary arteries with delayed opacification of the distal vasculature. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-Te) may correspond to the transmural dispersion of the repolarization and that increased Tp-Te interval and Tp-Te/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate the ventricular repolarization by using Tp-Te interval and Tp-Te/QT ratio in patients with CSF. This study included 50 CSF patients (40 male, mean age 48.6±12.5 years) and 40 control individuals (23 male, mean age 47.8±12.5 years). Tp-Te interval and Tp-Te/QT ratio were measured from the 12-lead electrocardiogram. These parameters were compared in groups. Baseline characteristics of the study groups were comparable. In electrocardiographic parameters analysis, QT and corrected QT were similar in CSF patients compared to the controls (357±35.2 vs 362±38.0 milliseconds and 419±25.8 vs 430±44.2 milliseconds, all p value >0.05). Tp-Te interval, Tp-Te/QT and Tp-Te/QTc ratio were significantly higher in CSF patients (85±13.7 vs 74±9.9 milliseconds and 0.24±0.03 vs 0.20±0.02 and 0.20±0.03 vs 0.17±0.02 all p value <0.001). Our study revealed that QTd, Tp-Te interval and Tp-Te/QT ratio are prolonged in patients with CSF.

Tp-e interval and Tp-e/QT ratio in patients with celiac disease.

PubMed

Demirtaş, K; Yayla, Ç; Yüksel, M; Açar, B; Ünal, S; Ertem, A G; Kaplan, M; Akpinar, M Y; Kiliç, Z M Y; Kayaçetin, E

2017-11-01

Celiac disease is a chronic immune-mediated disease of the small intestine. It has been known that dilated cardiomyopathy and ischemic coronary artery disease have become more frequent in patients with celiac disease. The aim of the study was to assess Tp-e interval and Tp-e/QT ratio in patients with celiac disease. This study was conducted at a single center in collaboration with gastroenterology and cardiology clinics. Between January 2014 and June 2015, a total of 76 consecutive patients were enrolled (38 patients with celiac disease and 38 control subjects). Tp-e interval, Tp-e/QT and Tp-e/QTc ratio were measured from the 12-lead electrocardiogram. Tp-e interval (64.2±11.0 vs. 44.5±6.0; p<0.001), Tp-e/QT ratio (0.18±0.02 vs. 0.13±0.02; p<0.001) and Tp-e/QTc ratio (0.16±0.02 vs. 0.11±0.01; p<0.001) were significantly higher in patients with celiac disease than control subjects. There was a significant positive correlation between Tp-e/QTc ratio and disease duration in patients with celiac disease (r=0.480, p=0.003) and also there was a significant positive correlation between Tp-e/QTc ratio and erythrocyte sedimentation rate (r=0.434, p<0.001). Our study showed that Tp-e interval, Tp-e/QT and Tp-e/QTc ratios were increased in patients with celiac disease. Whether these changes increase the risk of ventricular arrhythmia deserve further studies. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Platelet dysfunction associated with the novel Trp29Cys thromboxane A₂ receptor variant.

PubMed

Mumford, A D; Nisar, S; Darnige, L; Jones, M L; Bachelot-Loza, C; Gandrille, S; Zinzindohoue, F; Fischer, A-M; Mundell, S J; Gaussem, P

2013-03-01

Genetic variations that affect the structure of the thromboxane A2 receptor (TP receptor) provide insights into the function of this key platelet and vascular receptor, but are very rare in unselected populations. To determine the functional consequences of the TP receptor Trp29Cys (W29C) substitution. We performed a detailed phenotypic analysis of an index case (P1) with reduced platelet aggregation and secretion responses to TP receptor pathway activators, and a heterozygous TP receptor W29C substitution. An analysis of the variant W29C TP receptor expressed in heterologous cells was performed. Total TP receptor expression in platelets from P1 was similar to that of controls, but there was reduced maximum binding and reduced affinity of binding to the TP receptor antagonist [(3) H]SQ29548. HEK293 cells transfected with W29C TP receptor cDNA showed similar total TP receptor expression to wild-type (WT) controls. However, the TP receptor agonist U46619 was less potent at inducing rises in cytosolic free Ca(2+) in HEK293 cells expressing the W29C TP receptor than in WT controls, indicating reduced receptor function. Immunofluorescence microscopy and cell surface ELISA showed intracellular retention and reduced cell surface expression of the W29C TP receptor in HEK293 cells. Consistent with the platelet phenotype, both maximum binding and the affinity of binding of [(3) H]SQ29548 to the W29C TP receptor were reduced compared to WT controls. These findings extend the phenotypic description of the very rare disorder TP receptor deficiency, and show that the W29C substitution reduces TP receptor function by reducing surface receptor expression and by disrupting ligand binding. © 2012 International Society on Thrombosis and Haemostasis.

Smoking Cessation among Low-Socioeconomic Status and Disadvantaged Population Groups: A Systematic Review of Research Output.

PubMed

Courtney, Ryan J; Naicker, Sundresan; Shakeshaft, Anthony; Clare, Philip; Martire, Kristy A; Mattick, Richard P

2015-06-08

Smoking cessation research output should move beyond descriptive research of the health problem to testing interventions that can provide causal data and effective evidence-based solutions. This review examined the number and type of published smoking cessation studies conducted in low-socioeconomic status (low-SES) and disadvantaged population groups. A systematic database search was conducted for two time periods: 2000-2004 (TP1) and 2008-2012 (TP2). Publications that examined smoking cessation in a low-SES or disadvantaged population were coded by: population of interest; study type (reviews, non-data based publications, data-based publications (descriptive, measurement and intervention research)); and country. Intervention studies were coded in accordance with the Cochrane Effective Practice and Organisation of Care data collection checklist and use of biochemical verification of self-reported abstinence was assessed. 278 citations were included. Research output (i.e., all study types) had increased from TP1 27% to TP2 73% (χ²=73.13, p<0.001), however, the proportion of data-based research had not significantly increased from TP1 and TP2: descriptive (TP1=23% vs. TP2=33%) or intervention (TP1=77% vs. TP2=67%). The proportion of intervention studies adopting biochemical verification of self-reported abstinence had significantly decreased from TP1 to TP2 with an increased reliance on self-reported abstinence (TP1=12% vs. TP2=36%). The current research output is not ideal or optimal to decrease smoking rates. Research institutions, scholars and funding organisations should take heed to review findings when developing future research and policy.

Evaluation of Tp-e interval and Tp-e/QT ratio in patients with ankylosing spondylitis.

PubMed

Acar, Gurkan; Yorgun, Hikmet; Inci, Mehmet Fatih; Akkoyun, Murat; Bakan, Betul; Nacar, Alper Bugra; Dirnak, Imran; Cetin, Gozde Yildirim; Bozoglan, Orhan

2014-03-01

Ankylosing spondylitis (AS) is a chronic multi-systemic inflammatory rheumatic disorder. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the transmural dispersion of repolarization and that increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate ventricular repolarization by using Tp-e interval and Tp-e/QT ratio in patients with AS, and to assess the relation with inflammation. Sixty-two patients with AS and 50 controls were included. Tp-e interval and Tp-e/QT ratio were measured from a 12-lead electrocardiogram, and the Tp-e interval corrected for heart rate. The plasma level of high sensitive C-reactive protein (hsCRP) was measured. These parameters were compared between groups. In electrocardiographic parameters analysis, QT dispersion (QTd) and corrected QTd were significantly increased in AS patients compared to the controls (31.7 ± 9.6 vs 28.2 ± 7.4 and 35.8 ± 11.5 vs 30.6 ± 7.9 ms, P = 0.03 and P = 0.007, respectively). cTp-e interval and Tp-e/QT ratio were also significantly higher in AS patients (92.1 ± 10.2 vs 75.8 ± 8.4 and 0.22 ± 0.02 vs 0.19 ± 0.02 ms, all P values <0.001). cTp-e interval and Tp-e/QT ratio were significantly correlated with hsCRP (r = 0.63, P < 0.001 and r = 0.49, P < 0.001, respectively). Our study revealed that Tp-e interval and Tp-e/QT ratio were increased in AS patients. These electrocardiographic ventricular repolarization indexes were significantly correlated with the plasma level of hsCRP.

Evaluation of Tp-e interval and Tp-e/QT ratio in patients with ankylosing spondylitis.

PubMed

Acar, Gurkan; Yorgun, Hikmet; Inci, Mehmet Fatih; Akkoyun, Murat; Bakan, Betul; Nacar, Alper Bugra; Dirnak, Imran; Cetin, Gozde Yildirim; Bozoglan, Orhan

2013-04-12

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic multi-systemic inflammatory rheumatic disorder. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the transmural dispersion of repolarization and that increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate ventricular repolarization by using Tp-e interval and Tp-e/QT ratio in patients with AS, and to assess the relation with inflammation. METHODS: Sixty-two patients with AS and 50 controls were included. Tp-e interval and Tp-e/QT ratio were measured from a 12-lead electrocardiogram, and the Tp-e interval corrected for heart rate. The plasma level of high sensitive C-reactive protein (hsCRP) was measured. These parameters were compared between groups. RESULTS: In electrocardiographic parameters analysis, QT dispersion (QTd) and corrected QTd were significantly increased in AS patients compared to the controls (31.7 ± 9.6 vs 28.2 ± 7.4 and 35.8 ± 11.5 vs 30.6 ± 7.9 ms, P = 0.03 and P = 0.007, respectively). cTp-e interval and Tp-e/QT ratio were also significantly higher in AS patients (92.1 ± 10.2 vs 75.8 ± 8.4 and 0.22 ± 0.02 vs 0.19 ± 0.02 ms, all P values <0.001). cTp-e interval and Tp-e/QT ratio were significantly correlated with hsCRP (r = 0.63, P < 0.001 and r = 0.49, P < 0.001, respectively). CONCLUSIONS: Our study revealed that Tp-e interval and Tp-e/QT ratio were increased in AS patients. These electrocardiographic ventricular repolarization indexes were significantly correlated with the plasma level of hsCRP.

Evaluation of Electrocardiographic T-peak to T-end Interval in Subjects with Increased Epicardial Fat Tissue Thickness.

PubMed

Kaplan, Ozgur; Kurtoglu, Ertugrul; Nar, Gokay; Yasar, Erdogan; Gozubuyuk, Gokhan; Dogan, Cem; Boz, Ahmet Ugur; Hidayet, Sıho; Pekdemir, Hasan

2015-12-01

The association between periatrial adiposity and atrial arrhythmias has been shown in previous studies. However, there are not enough available data on the association between epicardial fat tissue (EFT) thickness and parameters of ventricular repolarization. Thus, we aimed to evaluate the association of EFT thickness with indices of ventricular repolarization by using T-peak to T-end (Tp-e) interval and Tp-e/QT ratio. The present study included 50 patients whose EFT thickness ≥ 9 mm (group 1) and 40 control subjects with EFT thickness < 9 mm (group 2). Transthoracic echocardiographic examination was performed in all participants. QT parameters, Tp-e intervals and Tp-e/QT ratio were measured from the 12-lead electrocardiogram. QTd (41.1 ± 2.5 vs 38.6 ± 3.2, p < 0.001) and corrected QTd (46.7 ± 4.7 vs 43.7 ± 4, p = 0.002) were significantly higher in group 1 when compared to group 2. The Tp-e interval (76.5 ± 6.3, 70.3 ± 6.8, p < 0.001), cTp-e interval (83.1 ± 4.3 vs. 76±4.9, p < 0.001), Tp-e/QT (0.20 ± 0.02 vs. 0.2 ± 0.02, p < 0.001) and Tp-e/QTc ratios (0.2 ± 0.01 vs. 0.18 ± 0.01, p < 0.001) were increased in group 1 in comparison to group 2. Significant positive correlations were found between EFT thickness and Tp-e interval (r = 0.548, p < 0.001), cTp-e interval (r = 0.259, p = 0.01), and Tp-e/QT (r = 0.662, p < 0.001) and Tp-e/QTc ratios (r = 0.560, p < 0.001). The present study shows that Tp-e and cTp-e interval, Tp-e/QT and Tp-e/QTc ratios were increased in subjects with increased EFT, which may suggest an increased risk of ventricular arrhythmia.

Enhancement of the spring East China precipitation response to tropical sea surface temperature variability

NASA Astrophysics Data System (ADS)

Zhang, Mengqi; Sun, Jianqi

2017-12-01

The boreal spring relationship between variabilities of East China precipitation (ECP) and tropical Ocean sea surface temperature (SST) during the period 1951-2014 is investigated in this study. The results show that the leading mode of the ECP variability exhibits an enhanced response to the anomalous El Niño-Southern Oscillation (ENSO)-like SST after the late 1970s, when the SST underwent a decadal change, with two positive centers over the eastern tropical Pacific (ETP) and tropical Indian Ocean (TIO). To further understand the relative roles of the ETP and TIO SST anomalies (SSTAs) in the variability of ECP after the late 1970s, partial regression and correlation methods are used. It is found that, without the contribution of the TIO, ETP SSTA plays a limited role in the variability of ECP after the late 1970s; comparatively, a significant correlation between TIO SST and ECP is identified during the same period, when the ETP signal is linearly removed. Physical analyses show that, after the late 1970s, the TIO SSTA affects East Asian atmospheric circulation in two ways: by exciting a zonal wave-train pattern over the mid-latitude Eurasian Continent and by inducing anomalous convection over the Maritime Continent. Via these two mechanisms, the TIO SST variability results in an anomalous East Asian trough and vertical motion over East China and consequently leads to anomalous precipitation over the region. The physical processes linking the ECP and TIO SST are confirmed by an atmospheric general circulation model experiment forced with idealized TIO warming.

Factors controlling the interannual variation of 30-60-day boreal summer intraseasonal oscillation over the Asian summer monsoon region

NASA Astrophysics Data System (ADS)

Li, Jianying; Mao, Jiangyu

2018-04-01

The 30-60-day boreal summer intraseasonal oscillation (BSISO) is a dominant variability of the Asian summer monsoon (ASM), with its intensity being quantified by intraseasonal standard deviations based on OLR data. The spatial and interannual variations of the BSISO intensity are identified via empirical orthogonal function (EOF) analysis for the period 1981-2014. The first EOF mode (EOF1) shows a spatially coherent enhancement or suppression of BSISO activity over the entire ASM region, and the interannual variability of this mode is related to the sea surface temperature anomaly (SSTA) contrast between the central-eastern North Pacific (CNP) and tropical Indian Ocean. In contrast, the second mode (EOF2) exhibits a seesaw pattern between the southeastern equatorial Indian Ocean (EIO) and equatorial western Pacific (EWP), with the interannual fluctuation linked with developing ENSO events. During strong years of EOF1 mode, the enhanced low-level westerlies induced by the summer-mean SSTA contrast between the warmer CNP and cooler tropical Indian Ocean tend to form a wetter moisture background over the eastern EIO, which interacts with intraseasonal low-level convergent flows, leading to stronger equatorial eastward propagation. The intensified easterly shear favors stronger northward propagation over the South Asian and Eastern Asian/Western North Pacific sectors, respectively. Opposite situation is for weak years. For interannual variations of EOF2 mode, the seesaw patterns with enhanced BSISO activity over the southeastern EIO while weakened activity over the EWP mostly occur in the La Niña developing summers, but inverse patterns appear in the El Niño developing summers.

Simulation of Rainfall Variability Over West Africa

NASA Astrophysics Data System (ADS)

Bader, J.; Latif, M.

The impact of sea surface temperature (SST) and vegetation on precipitation over West Africa is investigated with the atmospheric general circulation model ECHAM4.x/T42. Ensemble experiments -driven with observed SST- show that At- lantic SST has a significant influence on JJA precipitation over West Africa. Four- teen experiments were performed in which the climatological SST was enhanced or decreased by one Kelvin in certain ocean areas. Changing SST in the eastern tropi- cal Atlantic only caused significant changes along the Guinea Coast, with a positive SSTA increasing rainfall and a negative reducing it. The response was nearly linear. Changing SST in other ocean areas caused significant changes over West Africa, es- pecially in the Sahel area. The response is found to be non linear, with only negative SSTA leading to significant reduction in Sahel rainfall. Also, the impact of the SSTAs from the different ocean regions was not additive with respect to the rainfall. Four simulations with a coupled model (the simple dynamic vegetation model (SVege) and the ECHAM4-AGCM were coupled) were also performed, driven with observed SST from 1945 to 1998. The standard ECHAM-AGCM -forced by the same observed SST- was able to reproduce the drying trend from the fifties to the mid-eighties in the Sahel, but failed to mirror the magnitude of the rainfall anomalies. The coupled model was not only able to reproduce this drying trend, but was also able to better reproduce the amplitudes of the rainfall anomalies. The dynamic vegetation acted like an amplifier, increasing the SST induced rainfall anomalies.

Comparative reactivity of TpRu(L)(NCMe)Ph (L = CO or PMe3): impact of ancillary ligand l on activation of carbon-hydrogen bonds including catalytic hydroarylation and hydrovinylation/oligomerization of ethylene.

PubMed

Foley, Nicholas A; Lail, Marty; Lee, John P; Gunnoe, T Brent; Cundari, Thomas R; Petersen, Jeffrey L

2007-05-30

Complexes of the type TpRu(L)(NCMe)R [L = CO or PMe3; R = Ph or Me; Tp = hydridotris(pyrazolyl)borate] initiate C-H activation of benzene. Kinetic studies, isotopic labeling, and other experimental evidence suggest that the mechanism of benzene C-H activation involves reversible dissociation of acetonitrile, reversible benzene coordination, and rate-determining C-H activation of coordinated benzene. TpRu(PMe3)(NCMe)Ph initiates C-D activation of C6D6 at rates that are approximately 2-3 times more rapid than that for TpRu(CO)(NCMe)Ph (depending on substrate concentration); however, the catalytic hydrophenylation of ethylene using TpRu(PMe3)(NCMe)Ph is substantially less efficient than catalysis with TpRu(CO)(NCMe)Ph. For TpRu(PMe3)(NCMe)Ph, C-H activation of ethylene, to ultimately produce TpRu(PMe3)(eta3-C4H7), is found to kinetically compete with catalytic ethylene hydrophenylation. In THF solutions containing ethylene, TpRu(PMe3)(NCMe)Ph and TpRu(CO)(NCMe)Ph separately convert to TpRu(L)(eta3-C4H7) (L = PMe3 or CO, respectively) via initial Ru-mediated ethylene C-H activation. Heating mesitylene solutions of TpRu(L)(eta3-C4H7) under ethylene pressure results in the catalytic production of butenes (i.e., ethylene hydrovinylation) and hexenes.

Bullae

MedlinePlus

Habif TP. Principles of diagnosis and anatomy. In: Habif TP, ed. Clinical Dermatology . 6th ed. Philadelphia, PA: Elsevier; 2016:chap 1. Habif TP. Vesicular and bullous diseases. In: Habif TP, ed. ...

Cardiopulmonary responses of intratracheally instilled tire particles and constituent metal components

USGS Publications Warehouse

Gottipolu, R.R.; Landa, E.R.; Schladweiler, M.C.; McGee, J.K.; Ledbetter, A.D.; Richards, J.H.; Wallenborn, G.J.; Kodavanti, U.P.

2008-01-01

Tire and brake wear particles contain transition metals, and contribute to near-road PM. We hypothesized that acute cardiopulmonary injury from respirable tire particles (TP) will depend on the amount of soluble metals. Respirable fractions of two types of TP (TP1 and TP2) were analyzed for water and acid-leachable metals using ICP-AES. Both TP types contained a variety of transition metals, including zinc (Zn), copper (Cu), aluminum, and iron. Zn and Cu were detected at high levels in water-soluble fractions (TP2 > TP1). Male Wistar Kyoto rats (12-14 wk) were intratracheally instilled, in the first study, with saline, TP1 or TP2 (5 mg/kg), and in the second study, with soluble Zn, Cu (0.5 ??mol/kg), or both. Pulmonary toxicity and cardiac mitochondrial enzymes were analyzed 1 d, 1 wk, or 4 wk later for TP and 4 or 24 h later for metals. Increases in lavage fluid markers of inflammation and injury were observed at d 1 (TP2 > TP1), but these changes reversed by wk 1. No effects on cardiac enzymes were noted with either TP. Exposure of rats to soluble Zn and Cu caused marked pulmonary inflammation and injury but temporal differences were apparent (Cu effects peaked at 4 h and Zn at 24 h). Instillation of Zn, Cu, and Zn+ Cu decreased the activity of cardiac aconitase, isocitrate dehydrogenase, succinate dehydrogenase, cytochrome-c-oxidase and superoxide dismutase suggesting mitochondrial oxidative stress. The observed acute pulmonary toxicity of TP could be due to the presence of water soluble Zn and Cu. At high concentrations these metals may induce cardiac oxidative stress. Copyright ?? Informa Healthcare USA, Inc.

An Aggressive Surgical Approach Leads to Improved Survival in Patients With Gallbladder Cancer

PubMed Central

Dixon, Elijah; Vollmer, Charles M.; Sahajpal, Ajay; Cattral, Mark; Grant, David; Doig, Christopher; Hemming, Al; Taylor, Bryce; Langer, Bernard; Greig, Paul; Gallinger, Steven

2005-01-01

Objective: To determine if an aggressive surgical approach, with an increase in R0 resections, has resulted in improved survival for patients with gallbladder cancer. Summary Background Data: Many physicians express a relatively nihilistic approach to the treatment of gallbladder cancer; consensus among surgeons regarding the indications for a radical surgical approach has not been reached. Methods: A retrospective review of all patients with gallbladder cancer admitted during the past 12 years was conducted. Ninety-nine patients were identified. Cases treated during the 12-year period 1990 to 2002 were divided into 2 time-period (TP) cohorts, those treated in the first 6 years (TP1, N = 35) and those treated in the last 6 years (TP2, N = 64). Results: Disease stratification by stage and other demographic features were similar in the 2 time periods. An operation with curative intent was performed on 38 patients. Nine (26%) R0 resections were performed in TP1 and 24 (38%) in TP2. The number of liver resections, as well as the frequency of extrahepatic biliary resections, was greater in TP2 (P < 0.04). In both time periods, an R0 resection was associated with improved survival (P < 0.02 TP1, P < 0.0001 TP2). Overall survival of all patients in TP2 was significantly greater than in TP1 (P < 0.03), with a median survival of 9 months in TP1 and 17 months in TP2. The median 5-year survival in TP1 was 7%, and 35% in TP2. The surgical mortality rate for the entire cohort was 2%, with a 49% morbidity rate. Conclusions: A margin-negative, R0 resection leads to improved survival in patients with gallbladder cancer. PMID:15729060

Smoking Cessation among Low-Socioeconomic Status and Disadvantaged Population Groups: A Systematic Review of Research Output

PubMed Central

Courtney, Ryan J.; Naicker, Sundresan; Shakeshaft, Anthony; Clare, Philip; Martire, Kristy A.; Mattick, Richard P.

2015-01-01

Background: Smoking cessation research output should move beyond descriptive research of the health problem to testing interventions that can provide causal data and effective evidence-based solutions. This review examined the number and type of published smoking cessation studies conducted in low-socioeconomic status (low-SES) and disadvantaged population groups. Methods: A systematic database search was conducted for two time periods: 2000–2004 (TP1) and 2008–2012 (TP2). Publications that examined smoking cessation in a low-SES or disadvantaged population were coded by: population of interest; study type (reviews, non-data based publications, data-based publications (descriptive, measurement and intervention research)); and country. Intervention studies were coded in accordance with the Cochrane Effective Practice and Organisation of Care data collection checklist and use of biochemical verification of self-reported abstinence was assessed. Results: 278 citations were included. Research output (i.e., all study types) had increased from TP1 27% to TP2 73% (χ² = 73.13, p < 0.001), however, the proportion of data-based research had not significantly increased from TP1 and TP2: descriptive (TP1 = 23% vs. TP2 = 33%) or intervention (TP1 = 77% vs. TP2 = 67%). The proportion of intervention studies adopting biochemical verification of self-reported abstinence had significantly decreased from TP1 to TP2 with an increased reliance on self-reported abstinence (TP1 = 12% vs. TP2 = 36%). Conclusions: The current research output is not ideal or optimal to decrease smoking rates. Research institutions, scholars and funding organisations should take heed to review findings when developing future research and policy. PMID:26062037

TP53 dysfunction in CLL: Implications for prognosis and treatment.

PubMed

Te Raa, Gera D; Kater, Arnon P

2016-03-01

Despite the availability of novel targeted agents, TP53 defects remain the most important adverse prognostic factor in chronic lymphocytic leukemia (CLL). Detection of deletion of TP53 locus (17p deletion) by fluorescent in situ hybridization (FISH) has become standard and performed prior to every line of treatment as the incidence dramatically increases as relapses occur. As monoallelic mutations of TP53 equally affect outcome, novel methods are being developed to improve detection of TP53 defects and include next-generation sequencing (NGS) and functional assays. TP53 defects highly affect outcome of immunochemotherapy but also alter response durations of tyrosine kinase inhibitors. Although BCR-targeting agents and Bcl-2-inhibitos have achieved durable responses in some patients with TP53 defects, long-term follow-up is currently lacking. In this review biological and clinical consequences of TP53 dysfunction as well as applicability of currently available methods to detect TP53 defects are described. In addition, proposed novel therapeutic strategies specifically for patients with TP53 dysfunction are discussed. In summary, the only curative treatment option for TP53-defective CLL is still allogeneic hematopoietic stem cell transplantation. Other treatment strategies such as rationale combinations of agents with different (TP53 independent) targets, including kinase inhibitors and inhibitors of anti-apoptotic molecules but also immunomodulatory agents need to be further explored. Copyright © 2016 Elsevier Ltd. All rights reserved.

SCPS-TP: A Satellite-Enhanced TCP

NASA Technical Reports Server (NTRS)

Scott, Keith; Torgerson, Leigh

2004-01-01

This viewgraph presentation reviews the Space Communications Protocol Standard Transport Protocol (SCPS-TP) which is a satellite enhanced Transport Control Protocol (TCP). The contents include: 1) Purpose; 2) Background; 3) Stressed Communication Environments; 4) SCPS-TP Features; 5) SCPS-TP Performance; 6) Performance Enhancing Proxies (PEPs); and 7) Ongoing and Future SCPS-TP Work.

Testosterone and muscle hypertrophy in female rats

NASA Technical Reports Server (NTRS)

Kuhn, F. E.; Max, S. R.

1985-01-01

The effects of chronic treatment with testosterone propionate (TP) on compensatory muscle hypertropy in female rats are examined. The 48 female rats were placed in one of four test groups: (1) no overload (synergist removal), no TP, (2) overload, no TP, (3) no overload + TP, and (4) overload + TP. The technique used to administer the TP is described. The preparation of the plantaris muscle, the analysis of pyruvate oxidation and the determination of malate and lactate dehydrogenases and the noncollogen protein are explained. The results which reveal the effect of overload and TP on body weight, noncollogen protein concentration, lactate and malate dehydrogenase activities, and pyruvate oxidation are presented and discussed. It is concluded that in terms of body weight, protein content, pyruvate, glycolysis, and oxidative metabolisms chronic TP treatments do not change compensatory muscle hypertropy.

Temperature Regimes Impact Coral Assemblages along Environmental Gradients on Lagoonal Reefs in Belize

PubMed Central

Townsend, Joseph E.; Courtney, Travis A.; Aichelman, Hannah E.; Davies, Sarah W.; Lima, Fernando P.; Castillo, Karl D.

2016-01-01

Coral reefs are increasingly threatened by global and local anthropogenic stressors such as rising seawater temperature, nutrient enrichment, sedimentation, and overfishing. Although many studies have investigated the impacts of local and global stressors on coral reefs, we still do not fully understand how these stressors influence coral community structure, particularly across environmental gradients on a reef system. Here, we investigate coral community composition across three different temperature and productivity regimes along a nearshore-offshore gradient on lagoonal reefs of the Belize Mesoamerican Barrier Reef System (MBRS). A novel metric was developed using ultra-high-resolution satellite-derived estimates of sea surface temperatures (SST) to classify reefs as exposed to low (lowTP), moderate (modTP), or high (highTP) temperature parameters over 10 years (2003 to 2012). Coral species richness, abundance, diversity, density, and percent cover were lower at highTP sites relative to lowTP and modTP sites, but these coral community traits did not differ significantly between lowTP and modTP sites. Analysis of coral life history strategies revealed that highTP sites were dominated by hardy stress-tolerant and fast-growing weedy coral species, while lowTP and modTP sites consisted of competitive, generalist, weedy, and stress-tolerant coral species. Satellite-derived estimates of Chlorophyll-a (chl-a) were obtained for 13-years (2003–2015) as a proxy for primary production. Chl-a concentrations were highest at highTP sites, medial at modTP sites, and lowest at lowTP sites. Notably, thermal parameters correlated better with coral community traits between site types than productivity, suggesting that temperature (specifically number of days above the thermal bleaching threshold) played a greater role in defining coral community structure than productivity on the MBRS. Dominance of weedy and stress-tolerant genera at highTP sites suggests that corals utilizing these two life history strategies may be better suited to cope with warmer oceans and thus may warrant protective status under climate change. PMID:27606598

HPV-negative penile squamous cell carcinoma: disruptive mutations in the TP53 gene are common.

PubMed

Kashofer, Karl; Winter, Elke; Halbwedl, Iris; Thueringer, Andrea; Kreiner, Marisa; Sauer, Stefan; Regauer, Sigrid

2017-07-01

The majority of penile squamous cell carcinomas is caused by transforming human papilloma virus (HPV) infection. The etiology of HPV-negative cancers is unclear, but TP53 mutations have been implicated. Archival tissues of 108 invasive squamous cell carcinoma from a single pathology institution in a low-incidence area were analyzed for HPV-DNA and p16 ink4a overexpression and for TP53 mutations by ion torrent next-generation sequencing. Library preparation failed in 32/108 squamous cell carcinomas. Institutional review board approval was obtained. Thirty of 76 squamous cell carcinomas (43%; average 63 years) were HPV-negative with 8/33 squamous cell carcinomas being TP53 wild-type (24%; average 63 years). Twenty-five of 33 squamous cell carcinomas (76%; average 65 years) showed 32 different somatic TP53 mutations (23 missense mutations in exons 5-8, 6 nonsense, 1 frameshift and 2 splice-site mutations). Several hotspot mutations were detected multiple times (R175H, R248, R282, and R273). Eighteen of 19 squamous cell carcinomas with TP53 expression in immunohistochemistry had TP53 mutations. Fifty percent of TP53-negative squamous cell carcinomas showed mostly truncating loss-of-function TP53 mutations. Patients without mutations had longer survival (5 years: 86% vs 61%; 10 years: 60% vs 22%), but valid clinically relevant conclusions cannot be drawn due to different tumor stages and heterogeneous treatment of the cases presented in this study. Somatic TP53 mutations are a common feature in HPV-negative penile squamous cell carcinomas and offer an explanation for HPV-independent penile carcinogenesis. About half of HPV-negative penile cancers are driven by oncogenic activation of TP53, while a quarter is induced by loss of TP53 tumor suppressor function. Detection of TP53 mutations should be carried out by sequencing, as immunohistochemical TP53 staining could not identify all squamous cell carcinomas with TP53 mutations.

Prediction of utilizable true protein of mixed rations for sheep using an in vitro incubation technique.

PubMed

Li, Yuan-Xiao; Zhao, Guang-Yong

2007-04-01

The objective of the present experiment was to study the relationship between in vitro utilizable true protein (uTP) and in vivo-uTP of sheep rations by regression analysis. A further aim was to analyse if in vivo-uTP of mixed rations could be predicted by regression analysis between in vitro-uTP and in vivo-uTP, using N-retention of sheep as important evaluation criteria of protein value. Three adult male sheep (body weight [BW] 46 + 1.3 kg) fitted with rumen cannulas and simple T-type duodenal cannulas were fed with twelve typical rations with graded levels of crude protein and true protein in four experiments according a 3 x 3 Latin square design. Each experimental period included an adaptation (7 days), a N balance trial (4 days) and a collection of duodenal digesta (3 days). During collection of duodenal digesta, polyethylene glycol and chromium oxide were used as dual markers for the measurement of duodenal digesta flow and calculation of the in vivo-uTP of duodenal digesta. The in vitro-uTP of the rations was determined using the in vitro incubation technique of Zhao and Lebzien (2000). It was found that both in vitro-uTP intake and in vivo-uTP intake were significantly correlated with N-retention (p < 0.001) and that there was a significant linear relationship between the content of in vitro-uTP and in vivo-uTP in rations (p < 0.001). Therefore, it was concluded that the used in vitro incubation technique is suitable for the determination of in vitro-uTP of mixed rations for sheep, and that the amount of in vivo-uTP can be predicted by regression between in vitro-uTP and in vivo-uTP.

Evaluation of inhomogeneities of repolarization in patients with psoriasis vulgaris

PubMed Central

İnci, Sinan; Aksan, Gökhan; Nar, Gökay; Yüksel, Esra Pancar; Ocal, Hande Serra; Çapraz, Mustafa; Yüksel, Serkan; Şahin, Mahmut

2016-01-01

Introduction The arrhythmia potential has not been investigated adequately in psoriatic patients. In this study, we assessed the ventricular repolarization dispersion, using the Tp-e interval and the Tp-e/QT ratio, and investigated the association with inflammation. Material and methods Seventy-one psoriasis vulgaris patients and 70 age- and gender-matched healthy individuals were enrolled in the study. The severity of the disease was calculated using Psoriasis Area and Severity Index scoring. The QTd was defined as the difference between the maximum and minimum QT intervals. The Tp-e interval was defined as the interval from the peak of the T wave to the end of the T wave. The Tp-e interval was corrected for heart rate. The Tp-e/QT ratio was calculated using these measurements. Results There were no significant differences between the groups with respect to basal clinical and laboratory characteristics (p > 0.05). The Tp-e interval, the corrected Tp-e interval (cTp-e) and the Tp-e/QT ratio were also significantly higher in psoriasis patients compared to the control group (78.5 ±8.0 ms vs. 71.4 ±7.6 ms, p < 0.001, 86.3 ±13.2 ms vs. 77.6 ±9.0 ms, p < 0.001 and 0.21 ±0.02 vs. 0.19 ±0.02, p < 0.001 respectively). A significant correlation was detected between the cTp-e time and the Tp-e/QT ratio and the PASI score in the group of psoriatic patients (r = 0.51, p < 0.001; r = 0.59, p < 0.001, respectively). Conclusions In our study, we detected a significant increase in the Tp-e interval and the Tp-e/QT ratio in patients with psoriasis vulgaris. The Tp-e interval and the Tp-e/QT ratio may be predictors for ventricular arrhythmias in patients with psoriasis vulgaris. PMID:27904512

Temperature Regimes Impact Coral Assemblages along Environmental Gradients on Lagoonal Reefs in Belize.

PubMed

Baumann, Justin H; Townsend, Joseph E; Courtney, Travis A; Aichelman, Hannah E; Davies, Sarah W; Lima, Fernando P; Castillo, Karl D

2016-01-01

Coral reefs are increasingly threatened by global and local anthropogenic stressors such as rising seawater temperature, nutrient enrichment, sedimentation, and overfishing. Although many studies have investigated the impacts of local and global stressors on coral reefs, we still do not fully understand how these stressors influence coral community structure, particularly across environmental gradients on a reef system. Here, we investigate coral community composition across three different temperature and productivity regimes along a nearshore-offshore gradient on lagoonal reefs of the Belize Mesoamerican Barrier Reef System (MBRS). A novel metric was developed using ultra-high-resolution satellite-derived estimates of sea surface temperatures (SST) to classify reefs as exposed to low (lowTP), moderate (modTP), or high (highTP) temperature parameters over 10 years (2003 to 2012). Coral species richness, abundance, diversity, density, and percent cover were lower at highTP sites relative to lowTP and modTP sites, but these coral community traits did not differ significantly between lowTP and modTP sites. Analysis of coral life history strategies revealed that highTP sites were dominated by hardy stress-tolerant and fast-growing weedy coral species, while lowTP and modTP sites consisted of competitive, generalist, weedy, and stress-tolerant coral species. Satellite-derived estimates of Chlorophyll-a (chl-a) were obtained for 13-years (2003-2015) as a proxy for primary production. Chl-a concentrations were highest at highTP sites, medial at modTP sites, and lowest at lowTP sites. Notably, thermal parameters correlated better with coral community traits between site types than productivity, suggesting that temperature (specifically number of days above the thermal bleaching threshold) played a greater role in defining coral community structure than productivity on the MBRS. Dominance of weedy and stress-tolerant genera at highTP sites suggests that corals utilizing these two life history strategies may be better suited to cope with warmer oceans and thus may warrant protective status under climate change.

TP53 mutation and survival in aggressive B cell lymphoma.

PubMed

Zenz, Thorsten; Kreuz, Markus; Fuge, Maxi; Klapper, Wolfram; Horn, Heike; Staiger, Annette M; Winter, Doris; Helfrich, Hanne; Huellein, Jennifer; Hansmann, Martin-Leo; Stein, Harald; Feller, Alfred; Möller, Peter; Schmitz, Norbert; Trümper, Lorenz; Loeffler, Markus; Siebert, Reiner; Rosenwald, Andreas; Ott, German; Pfreundschuh, Michael; Stilgenbauer, Stephan

2017-10-01

TP53 is mutated in 20-25% of aggressive B-cell lymphoma (B-NHL). To date, no studies have addressed the impact of TP53 mutations in prospective clinical trial cohorts. To evaluate the impact of TP53 mutation to current risk models in aggressive B-NHL, we investigated TP53 gene mutations within the RICOVER-60 trial. Of 1,222 elderly patients (aged 61-80 years) enrolled in the study and randomized to six or eight cycles of CHOP-14 with or without Rituximab (NCT00052936), 265 patients were analyzed for TP53 mutations. TP53 mutations were demonstrated in 63 of 265 patients (23.8%). TP53 mutation was associated with higher LDH (65% vs. 37%; p < 0.001), higher international prognostic index-Scores (IPI 4/5 27% vs. 12%; p = 0.025) and B-symptoms (41% vs. 24%; p = 0.011). Patients with TP53 mutation were less likely to obtain a complete remission CR/CRu (CR unconfirmed) 61.9% (mut) vs. 79.7% (wt) (p = 0.007). TP53 mutations were associated with decreased event-free (EFS), progression-free (PFS) and overall survival (OS) (median observation time of 40.2 months): the 3 year EFS, PFS and OS were 42% (vs. 60%; p = 0.012), 42% (vs. 67.5%; p < 0.001) and 50% (vs. 76%; p < 0.001) for the TP53 mutation group. In a Cox proportional hazard analysis adjusting for IPI-factors and treatment arms, TP53 mutation was shown to be an independent predictor of EFS (HR 1.5), PFS (HR 2.0) and OS (HR 2.3; p < 0.001). TP53 mutations are independent predictors of survival in untreated patients with aggressive CD20+ lymphoma. TP53 mutations should be considered for risk models in DLBCL and strategies to improve outcome for patients with mutant TP53 must be developed. © 2017 UICC.

Protein and siRNA delivery by transportan and transportan 10 into colorectal cancer cell lines.

PubMed

Wierzbicki, Piotr M; Kogut-Wierzbicka, Marzena; Ruczynski, Jaroslaw; Siedlecka-Kroplewska, Kamila; Kaszubowska, Lucyna; Rybarczyk, Agnieszka; Alenowicz, Magdalena; Rekowski, Piotr; Kmiec, Zbigniew

2014-01-01

Cell penetrating peptides (CPPs) have the ability to translocate through cell membranes with high efficiency and therefore can introduce biological agents with pharmaceutical properties into the cell. Transportan (TP) and its shorter analog transportan 10 (TP10) are among the best studied CPPs, however, their effects on viability of and cargo introduction into colorectal cancer (CRC) cells have yet not been investigated. The aim of our study was to evaluate the cytotoxic effects of TP and TP10 on representative CRC lines and the efficiency of protein (streptavidin) and siRNA cargo delivery by TP-biotinylated derivatives (TP-biot). HT29 (early stage CRC model) and HCT116 (metastatic CRC model) cell lines were incubated with TP, TP10, TP-biot1, TP-biot13 and TP10-biot1. The effects of studied CPPs on cell viability and cell cycle were assessed by MTT and annexin V assays. The uptake of streptavidin-FITC complex into cells was determined by flow cytometry and fluorescence microscopy, with the inhibition of cellular vesicle trafficking by brefeldin A. The efficiency of siRNA for SASH1 gene delivery was measured by quantitative PCR (qPCR). Since up to 10 µM concentrations of each CPP showed no significant cytotoxic effect, the concentrations of 0.5-5 µM were used for further analyses. Within this concentration range none of the studied CPPs affected cell viability and cell cycle. The efficient and endocytosis-independent introduction of streptavidin-FITC complex into cells was observed for TP10-biot1 and TP-biot1 with the cytoplasmic location of the fluorescent cargo; decreased SASH1 mRNA level was noticed with the use of siRNA and analyzed CPPs. We conclude that TP, TP10 and their biotinylated derivatives can be used as efficient delivery vehicles of small and large cargoes into CRC cells.

The microphysical properties of convective precipitation over the Tibetan Plateau by a high-resolution cloud-resolving simulation

NASA Astrophysics Data System (ADS)

Gao, W.; Liu, L.; Hu, Z.

2017-12-01

The microphysical properties of precipitating convective systems over the Tibetan Plateau (TP) are unique because of the extremely high topography and special atmospheric conditions. In this study, the ground-based millimeter cloud radar and optical disdrometer observations during the Third Tibetan Plateau Atmospheric Scientific Experiment (TIPEX-III), and the high-resolution (600-m horizontal grid size) simulations with the Chinese Academy of Meteorological Sciences microphysics (CAMS) are used to investigate the microphysics and precipitation mechanism of a convection event on 24 July 2014. The model reasonably reproduces the spatial distribution of 24-h accumulated rainfall yet the temporal evolution of rainfall rate has a two hours delay. The simulated raindrop size distribution (RSD) is in general agreement with the disdrometer measurement, and the number concentration for small raindrop is a certain degree overestimated. The RSD over the TP is wider than that over plain at the same latitude, implying that the precipitation may be more easily produced in the former. Results demonstrate that the leading ice crystal microphysical processes are the depositional growth of ice crystal and autoconversion of ice crystal to snow. The dominant source term of snow/graupel in convection is the accretion of cloud water by snow/graupel (riming) due to the plentiful supercooled cloud water over there. Note that the accretion of snow by rain to form graupel has a great contribution to graupel number concentration as the existence of large liquid particles in cold region over the TP. In addition, the microphysics-produced graupel fall out completely through the sedimentation process and accumulate near the melting layer with the rate of 0.09 g kg-1s-1. They then melt immediately to form rain water in warm region and half of them can finally reach the ground to form precipitation (the rest evaporated). Furthermore, the water vapor budgets analyses reveal that the surface evaporation is the principal source of water vapor at the beginning of convection. While during the development of convection, the total vapor flux convergence (horizontal and vertical) supplies about 90% of the net condensation (condensation and deposition) and has the similar phase with the area-averaged rainfall rate, indicating its important role in TP convective precipitation.

[Evaluation of the Performance of Two Kinds of Anti-TP Enzyme-Linked Immunosorbent Assay].

PubMed

Gao, Nan; Huang, Li-Qin; Wang, Rui; Jia, Jun-Jie; Wu, Shuo; Zhang, Jing; Ge, Hong-Wei

2018-06-01

To evaluate the accuracy and precision of 2 kinds of anti-treponema pallidum (anti-TP) ELISA reagents in our laboratory for detecting the anti-TP in voluntary blood donors, so as to provide the data support for use of ELISA reagents after introduction of chemiluminescene immunoassay (CLIA). The route detection of anti-TP was performed by using 2 kinds of ELISA reagents, then 546 responsive positive samples detected by anti-TP ELISA were collected, and the infections status of samples confirmed by treponema pallidum particle agglutination (TPPA) test was identified. The confirmed results of responsive samples detected by 2 kinds of anti-TP ELISA reagents were compared, the accuracy of 2 kinds of anti-TP ELISA reagents was analyzed by drawing ROC and comparing area under curve (AUC), and precision of 2 kinds of anti-TP ELISA reagents was compared by statistical analysis of quality control data from 7.1 2016 to 6.30 2017. There were no statistical difference in confirmed positive rate of responsive samples and weak positive samples between 2 kinds of anti-TP ELISA reagents. The responsive samples detected by 2 kinds of anti-TP ELISA reagents accounted for 85.53%(467/546) of all responsive samples, the positive rate confirmed by TPPA test was 82.87%. 44 responsive samples detected by anti-TP ELISA reagent A and 35 responsive samples detected by anti-TP ELISA reagent B were confirmed to be negative by TPPA test. Comparison of AUC showed that the accuracy of 2 kinds of anti-TP ELISA reagents was more high, the difference between 2 reagents was not statistically significant. The coefficient of variation (CV) of anti-TP ELISA reagent A and B was 14.98% and 18.04% respectively, which met the precision requirement of ELISA test. The accuracy and precision of 2 kinds of anti-TP ELISA reagents used in our laboratory are similar, and using any one of anti-TP ELISA reagents all can satisfy the requirements of blood screening.

Effects of thymidine phosphorylase on tumor aggressiveness and 5-fluorouracil sensitivity in cholangiocarcinoma

PubMed Central

Thanasai, Jongkonnee; Limpaiboon, Temduang; Jearanaikoon, Patcharee; Sripa, Banchob; Pairojkul, Chawalit; Tantimavanich, Srisurang; Miwa, Masanao

2010-01-01

AIM: To evaluate the role of thymidine phosphorylase (TP) in cholangiocarcinoma using small interfering RNA (siRNA). METHODS: A human cholangiocarcinoma-derived cell line KKU-M139, which has a naturally high level of endogenous TP, had TP expression transiently knocked down using siRNA. Cell growth, migration, in vitro angiogenesis, apoptosis, and cytotoxicity were assayed in TP knockdown and wild-type cell lines. RESULTS: TP mRNA and protein expression were decreased by 87.1% ± 0.49% and 72.5% ± 3.2%, respectively, compared with control cells. Inhibition of TP significantly decreased migration of KKU-M139, and suppressed migration and tube formation of human umbilical vein endothelial cells. siRNA also reduced the ability of TP to resist hypoxia-induced apoptosis, while suppression of TP reduced the sensitivity of KKU-M139 to 5-fluorouracil. CONCLUSION: Inhibition of TP may be beneficial in decreasing angiogenesis-dependent growth and migration of cholangiocarcinoma but may diminish the response to 5-fluorouracil chemotherapy. PMID:20355241

Recombinant Treponema pallidum Protein Tp0965 Activates Endothelial Cells and Increases the Permeability of Endothelial Cell Monolayer

PubMed Central

Zhang, Rui-Li; Zhang, Jing-Ping; Wang, Qian-Qiu

2014-01-01

The recombinant Treponema pallidum protein Tp0965 (rTp0965), one of the many proteins derived from the genome of T. pallidum subsp. pallidum, shows strong immunogenicity and immunoreactivity. In this study, we investigated the effects of rTp0965 on the endothelial barrier. Treatment of human umbilical vein endothelial cells (HUVECs) with rTp0965 resulted in increased levels of ICAM-1, E-selectin, and MCP-1 mRNA and protein expression. These increases contributed to the adhesion and chemataxis of monocytes (THP-1 cells) to HUVECs preincubated with rTp0965. In addition, rTp0965 induced reorganization of F-actin and decreased expression of claudin-1 in HUVECs. Interestingly, inhibition of the RhoA/ROCK signal pathway protected against rTp0965-induced higher endothelial permeability as well as transendothelial migration of monocytes. These data indicate that Tp0965 protein may play an important role in the immunopathogenesis of syphilis. PMID:25514584

Panobinostat plus bortezomib and dexamethasone: impact of dose intensity and administration frequency on safety in the PANORAMA 1 trial.

PubMed

San-Miguel, Jesús F; Hungria, Vania T M; Yoon, Sung-Soo; Beksac, Meral; Dimopoulos, Meletios A; Elghandour, Ashraf; Jedrzejczak, Wieslaw W; Guenther, Andreas; Na Nakorn, Thanyaphong; Siritanaratkul, Noppadol; Schlossman, Robert L; Hou, Jian; Moreau, Philippe; Lonial, Sagar; Lee, Jae-Hoon; Einsele, Hermann; Salwender, Hans; Sopala, Monika; Redhu, Suman; Paul, Sofia; Corrado, Claudia; Richardson, Paul G

2017-10-01

Panobinostat in combination with bortezomib and dexamethasone demonstrated a significant and clinically meaningful progression-free survival benefit compared with placebo, bortezomib and dexamethasone in the phase 3 PANORAMA 1 (Panobinostat Oral in Multiple Myeloma 1) trial. Despite this benefit, patients in the panobinostat arm experienced higher rates of adverse events (AEs) and higher rates of discontinuation due to AEs. This PANORAMA 1 subanalysis examined AEs between 2 treatment phases of the study (TP1 and TP2), in which administration frequency of bortezomib and dexamethasone differed per protocol. The incidences of several key AEs were lower in both arms following the planned reduction of bortezomib dosing frequency in TP2. In the panobinostat arm, rates of thrombocytopenia (grade 3/4: TP1, 56·7%; TP2, 6·0%), diarrhoea (grade 3/4: TP1, 24·1%; TP2, 7·1%), and fatigue (grade 3/4: TP1, 16·3%; TP2, 1·8%) were lower in TP2 compared with TP1. Dose intensity analysis of panobinostat and bortezomib by cycle in the panobinostat arm showed reductions of both agent doses during cycles 1-4 due to dose adjustments for AEs. Exposure-adjusted analysis demonstrated a reduction in thrombocytopenia frequency in TP1 following dose adjustment. These results suggest that optimization of dosing with this regimen could improve tolerability, potentially leading to improved patient outcomes. © 2017 John Wiley & Sons Ltd.

Spatial-temporal variations of dominant drought/flood modes and the associated atmospheric circulation and ocean events in rainy season over the east of China

NASA Astrophysics Data System (ADS)

Huang, Shaoni; Huang, Fei

2012-06-01

By using Season-reliant Empirical Orthogonal Function (S-EOF) analysis, three dominant modes of the spatial-temporal evolution of the drought/flood patterns in the rainy season over the east of China are revealed for the period of 1960-2004. The first two leading modes occur during the turnabout phase of El Niño-Southern Oscillation (ENSO) decaying year, but the drought/flood patterns in the rainy season over the east of China are different due to the role of the Indian Ocean (IO). The first leading mode appears closely correlated with the ENSO events. In the decaying year of El Niño, the associated western North Pacific (WNP) anticyclone located over the Philippine Sea persists from the previous winter to the next early summer, transports warm and moist air toward the southern Yangtze River in China, and leads to wet conditions over this entire region. Therefore, the precipitation anomaly in summer exhibits a `Southern Flood and Northern Drought' pattern over East China. On the other hand, the basin-wide Indian Ocean sea surface temperature anomaly (SSTA) plays a crucial role in prolonging the impact of ENSO on the second mode during the ENSO decaying summer. The Indian Ocean basin mode (IOBM) warming persists through summer and unleashes its influence, which forces a Matsuno-Gill pattern in the upper troposphere. Over the subtropical western North Pacific, an anomalous anticyclone forms in the lower troposphere. The southerlies on the northwest flank of this anticyclone increase the moisture transport onto central China, leading to abundant rainfall over the middle and lower reaches of the Yangtze River and Huaihe River valleys. The anomalous anticyclone causes dry conditions over South China and the South China Sea (SCS). The precipitation anomaly in summer exhibits a `Northern Flood and Southern Drought' pattern over East China. Therefore, besides the ENSO event the IOBM is an important factor to influence the drought/flood patterns in the rainy season over the east of China. The third mode is positively correlated with the tropical SSTA in the Indian Ocean from the spring of preceding year(-1) to the winter of following year(+1), but not related to the ENSO events. The positive SSTA in the South China Sea and the Philippine Sea persists from spring to autumn, leading to weak north-south and land-sea thermal contrasts, which may weaken the intensity of the East Asia summer monsoon. The weakened rainfall over the northern Indian monsoon region may link to the third spatial mode through the `Silk Road' teleconnection or a part of circumglobal teleconnection (CGT). The physical mechanisms that reveal these linkages remain elusive and invite further investigation.

Nuclear TP53: An unraveled function as transcriptional repressor of PINK1.

PubMed

Checler, Frédéric; Goiran, Thomas; Alves da Costa, Cristine

2018-05-11

The tumor suppressor TP53/p53 is a key protein in both neurodegenerative diseases and cancer. Thus, TP53-linked cell death appears exacerbated in several age-related neuropathologies, while TP53 mutation-associated phenotypes indicate a loss of function accounting for approximately half of cancers. Thus, TP53 plays a pivotal role in these phenotypically distinct pathologies, a hypothesis reinforced by recent epidemiological studies suggesting an opposite risk to develop one type of pathology relative to the other. Dysfunctions in mitophagic processes also occur in both types of pathologies and again, TP53 has been proposed as one of the regulators of this cellular process. The consensus view postulates that TP53 exerts both anti- and pro-autophagy functions that are directly driven by a specific subcellular localization. Thus, TP53 positively modulates autophagy via the transcriptional control of several genes while it is acknowledged that its anti-autophagy phenotype is exclusively linked to a transcription-independent cytosolic control of an AMPK-MTOR cascade. Our study indicates that TP53 can also downregulate the specialized autophagy-related mitophagy response via the transcriptional repression of PINK1. This is the first demonstration of an anti-mitophagic control by nuclear TP53.

TP53INP1 is a novel p73 target gene that induces cell cycle arrest and cell death by modulating p73 transcriptional activity.

PubMed

Tomasini, Richard; Seux, Mylène; Nowak, Jonathan; Bontemps, Caroline; Carrier, Alice; Dagorn, Jean-Charles; Pébusque, Marie-Josèphe; Iovanna, Juan L; Dusetti, Nelson J

2005-12-08

TP53INP1 is an alternatively spliced gene encoding two nuclear protein isoforms (TP53INP1alpha and TP53INP1beta), whose transcription is activated by p53. When overexpressed, both isoforms induce cell cycle arrest in G1 and enhance p53-mediated apoptosis. TP53INP1s also interact with the p53 gene and regulate p53 transcriptional activity. We report here that TP53INP1 expression is induced during experimental acute pancreatitis in p53-/- mice and in cisplatin-treated p53-/- mouse embryo fibroblasts (MEFs). We demonstrate that ectopic expression of p73, a p53 homologue, leads to TP53INP1 induction in p53-deficient cells. In turn, TP53INP1s alters the transactivation capacity of p73 on several p53-target genes, including TP53INP1 itself, demonstrating a functional association between p73 and TP53INP1s. Also, when overexpressed in p53-deficient cells, TP53INP1s inhibit cell growth and promote cell death as assessed by cell cycle analysis and colony formation assays. Finally, we show that TP53INP1s potentiate the capacity of p73 to inhibit cell growth, that effect being prevented when the p53 mutant R175H is expressed or when p73 expression is blocked by a siRNA. These results suggest that TP53INP1s are functionally associated with p73 to regulate cell cycle progression and apoptosis, independently from p53.

Activation of heteroallenes by coordinatively unsaturated nickel(ii) alkyl complexes supported by the hydrotris(3-phenyl-5-methyl)pyrazolyl borate (Tp(Ph,Me)) ligand.

PubMed

Abubekerov, Mark; Eymann, Léonard Y M; Gianetti, Thomas L; Arnold, John

2016-10-07

Activation of sulfur containing heteroallenes by nickel(ii) alkyl complexes supported by the bulky hydrotris(3-phenyl-5-methylpyrazolyl)borate (Tp(Ph,Me)) ligand is described. Exposure of Tp(Ph,Me)NiCH2Ph (1a) and Tp(Ph,Me)NiCH2Si(CH3)3 (1b) to CS2 resulted in formation of the insertion products Tp(Ph,Me)Ni(η(2)-CS2)CH2Ph (2a) and Tp(Ph,Me)Ni(η(2)-CS2)CH2Si(CH3)3 (2b) in moderate yields. Reaction of 1a and MeNCS produced two species in a 1 : 1 ratio, identified as Tp(Ph,Me)Ni(η(2)-MeNC)CH2Ph (3) and Tp(Ph,Me)Ni(η(2)-MeNCS)SCH2Ph (4). Isolation of the unexpected insertion product (3) prompted an investigation into the activity of 1a-b in the presence of isocyanides (i.e.(t)BuNC), which resulted in isolation of Tp(Ph,Me)Ni(η(2-t)BuNC)CH2Ph (5a) and Tp(Ph,Me)Ni(η(2-t)BuNC)CH2Si(CH3)3 (5b). Similarly, reaction of 1a with OCS led to the isolation of a rare example of a Ni(i) carbonyl species Tp(Ph,Me)NiCO (6). Alternatively, complex 6 was also formed by exposure of 1a-b to an atmosphere of CO. Isolation of the intermediate species (Tp(Ph,Me)Ni(η(2)-CO)CH2TMS (7b) and Tp(Ph,Me)Ni(CO)(C(O)R, (8a-b) with R = Ph, TMS)) shed light on the formation of such species.

Significance of TP53 Mutation in Wilms Tumors with Diffuse Anaplasia: A Report from the Children's Oncology Group.

PubMed

Ooms, Ariadne H A G; Gadd, Samantha; Gerhard, Daniela S; Smith, Malcolm A; Guidry Auvil, Jaime M; Meerzaman, Daoud; Chen, Qing-Rong; Hsu, Chih Hao; Yan, Chunhua; Nguyen, Cu; Hu, Ying; Ma, Yussanne; Zong, Zusheng; Mungall, Andrew J; Moore, Richard A; Marra, Marco A; Huff, Vicki; Dome, Jeffrey S; Chi, Yueh-Yun; Tian, Jing; Geller, James I; Mullighan, Charles G; Ma, Jing; Wheeler, David A; Hampton, Oliver A; Walz, Amy L; van den Heuvel-Eibrink, Marry M; de Krijger, Ronald R; Ross, Nicole; Gastier-Foster, Julie M; Perlman, Elizabeth J

2016-11-15

To investigate the role and significance of TP53 mutation in diffusely anaplastic Wilms tumors (DAWTs). All DAWTs registered on National Wilms Tumor Study-5 (n = 118) with available samples were analyzed for TP53 mutations and copy loss. Integrative genomic analysis was performed on 39 selected DAWTs. Following analysis of a single random sample, 57 DAWTs (48%) demonstrated TP53 mutations, 13 (11%) copy loss without mutation, and 48 (41%) lacked both [defined as TP53-wild-type (wt)]. Patients with stage III/IV TP53-wt DAWTs (but not those with stage I/II disease) had significantly lower relapse and death rates than those with TP53 abnormalities. In-depth analysis of a subset of 39 DAWTs showed seven (18%) to be TP53-wt: These demonstrated gene expression evidence of an active p53 pathway. Retrospective pathology review of TP53-wt DAWT revealed no or very low volume of anaplasia in six of seven tumors. When samples from TP53-wt tumors known to contain anaplasia histologically were available, abnormal p53 protein accumulation was observed by immunohistochemistry. These data support the key role of TP53 loss in the development of anaplasia in WT, and support its significant clinical impact in patients with residual anaplastic tumor following surgery. These data also suggest that most DAWTs will show evidence of TP53 mutation when samples selected for the presence of anaplasia are analyzed. This suggests that modifications of the current criteria to also consider volume of anaplasia and documentation of TP53 aberrations may better reflect the risk of relapse and death and enable optimization of therapeutic stratification. Clin Cancer Res; 22(22); 5582-91. ©2016 AACR. ©2016 American Association for Cancer Research.

Significance of TP53 Mutation in Wilms Tumors with Diffuse Anaplasia: A Report from the Children’s Oncology Group

PubMed Central

Ooms, Ariadne H.A.G.; Gadd, Samantha; Gerhard, Daniela S.; Smith, Malcolm A.; Guidry Auvil, Jaime M.; Meerzaman, Daoud; Chen, Qing-Rong; Hsu, Chih Hao; Yan, Chunhua; Nguyen, Cu; Hu, Ying; Ma, Yussanne; Zong, Zusheng; Mungall, Andrew J.; Moore, Richard A.; Marra, Marco A.; Huff, Vicki; Dome, Jeffrey S.; Chi, Yueh-Yun; Tian, Jing; Geller, James I.; Mullighan, Charles G.; Ma, Jing; Wheeler, David A.; Hampton, Oliver A.; Walz, Amy L.; van den Heuvel-Eibrink, Marry M.; de Krijger, Ronald R.; Ross, Nicole; Gastier-Foster, Julie M.; Perlman, Elizabeth J.

2016-01-01

Purpose To investigate the role and significance of TP53 mutation in diffusely anaplastic Wilms tumor (DAWT). Experimental Design All DAWTs registered on National Wilms Tumor Study-5 (n=118) with available samples were analyzed for TP53 mutations and copy loss. Integrative genomic analysis was performed on 39 selected DAWTs. Results Following analysis of a single random sample, 57 DAWT (48%) demonstrated TP53 mutations, 13(11%) copy loss without mutation, and 48(41%) lacked both (defined as TP53-wildtype (wt)). Patients with Stage III/IV TP53-wt DAWTs (but not those with Stage I/II disease) had significantly lower relapse and death rates than those with TP53 abnormalities. In-depth analysis of a subset of 39 DAWT showed 7(18%) to be TP53-wt: these demonstrated gene expression evidence of an active p53 pathway. Retrospective pathology review of TP53-wt DAWT revealed no or very low volume of anaplasia in 6/7 tumors. When samples from TP53-wt tumors known to contain anaplasia histologically were available, abnormal p53 protein accumulation was observed by immunohistochemistry. Conclusion These data support the key role of TP53 loss in the development of anaplasia in WT, and support its significant clinical impact in patients with residual anaplastic tumor following surgery. These data also suggest that most DAWTs will show evidence of TP53 mutation when samples selected for the presence of anaplasia are analyzed. This suggests that modifications of the current criteria to also consider volume of anaplasia and documentation of TP53 aberrations may better reflect the risk of relapse and death and enable optimization of therapeutic stratification. PMID:27702824

Five Different Piscidins from Nile Tilapia, Oreochromis niloticus: Analysis of Their Expressions and Biological Functions

PubMed Central

Peng, Kuan-Chieh; Lee, Shu-Hua; Hour, Ai-Ling; Pan, Chieh-Yu; Lee, Lin-Han; Chen, Jyh-Yih

2012-01-01

Piscidins are antimicrobial peptides (AMPs) that play important roles in helping fish resist pathogenic infections. Through comparisons of tilapia EST clones, the coding sequences of five piscidin-like AMPs (named TP1∼5) of Nile tilapia, Oreochromis niloticus, were determined. The complete piscidin coding sequences of TP1, -2, -3, -4, and -5 were respectively composed of 207, 234, 231, 270, and 195 bases, and each contained a translated region of 68, 77, 76, 89, and 64 amino acids. The tissue-specific, Vibrio vulnificus stimulation-specific, and Streptococcus agalactiae stimulation-specific expressions of TP2, -3, and -4 mRNA were determined by a comparative RT-PCR. Results of the tissue distribution analysis revealed high expression levels of TP2 mRNA in the skin, head kidneys, liver, and spleen. To study bacterial stimulation, S. agalactiae (SA47) was injected, and the TP4 transcript was upregulated by >13-fold (compared to the wild-type (WT) control, without injection) and was 60-fold upregulated (compared to the WT control, without injection) 24 h after the S. agalactiae (SA47) injection in the spleen and gills. Synthesized TP3 and TP4 peptides showed antimicrobial activities against several bacteria in this study, while the synthesized TP1, -2, and -5 peptides did not. The synthesized TP2, -3, and -4 peptides showed hemolytic activities and synthesized TP3 and TP4 peptides inhibited tilapia ovary cell proliferation with a dose-dependent effect. In summary, the amphiphilic α-helical cationic peptides of TP3 and TP4 may represent novel and potential antimicrobial agents for further peptide drug development. PMID:23226256

Discordant Syphilis Immunoassays in Pregnancy: Perinatal Outcomes and Implications for Clinical Management.

PubMed

Mmeje, Okeoma; Chow, Joan M; Davidson, Lisette; Shieh, Jennifer; Schapiro, Jeffrey M; Park, Ina U

2015-10-01

The reverse sequence algorithm is often used for prenatal syphilis screening by high-volume laboratories, beginning with a treponemal test such as the chemiluminescence immunoassay (CIA), followed by testing of CIA-positive (CIA(+)) specimens with the rapid plasma reagin test (RPR). The clinical significance of discordant serology (CIA(+)/RPR(-)) for maternal and neonatal outcomes is unknown. From August 2007 to August 2010, all pregnant women at Kaiser Permanente Northern California with discordant treponemal serology underwent reflexive testing with Treponema pallidum particle agglutination assay (TP-PA) and were categorized as "TP-PA confirmed" (CIA(+)/RPR(-)/TP-PA(+)) or "isolated CIA positive" (CIA(+)/RPR(-)/TP-PA(-)). Demographic variables and clinical data were abstracted from the medical record and compared by TP-PA status. Of 194 pregnant women, 156 (80%) were CIA(+)/RPR(-)/TP-PA(-) and 38 (20%) were CIA(+)/RPR(-)/TP-PA(+). Among the 77 (49%) CIA(+)/RPR(-)/TP-PA(-) women who were retested, 53% became CIA(-). CIA(+)/RPR(-)/TP-PA(+) (n = 38) women were more likely to be older, have a prior history of sexually transmitted infections, and receive treatment for syphilis during pregnancy than women who were CIA(+)/RPR(-)/TP-PA(-) (all P < .005). Most pregnancies (189/194 [97.5%]) resulted in a live birth; there was no difference in birth outcomes according to TP-PA status and no stillbirths attributable to syphilis. Most pregnant women with discordant serology were CIA(+)/RPR(-)/TP-PA(-); more than half who were retested became CIA(-). CIA(+)/RPR(-)/TP-PA(-) serology in pregnancy is likely to be falsely positive. Reflexive testing of discordant specimens with TP-PA is important to stratify risk given the likelihood of false-positive results in this population. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma.

PubMed

Zhukova, Nataliya; Ramaswamy, Vijay; Remke, Marc; Martin, Dianna C; Castelo-Branco, Pedro; Zhang, Cindy H; Fraser, Michael; Tse, Ken; Poon, Raymond; Shih, David J H; Baskin, Berivan; Ray, Peter N; Bouffet, Eric; Dirks, Peter; von Bueren, Andre O; Pfaff, Elke; Korshunov, Andrey; Jones, David T W; Northcott, Paul A; Kool, Marcel; Pugh, Trevor J; Pomeroy, Scott L; Cho, Yoon-Jae; Pietsch, Torsten; Gessi, Marco; Rutkowski, Stefan; Bognár, Laszlo; Cho, Byung-Kyu; Eberhart, Charles G; Conter, Cecile Faure; Fouladi, Maryam; French, Pim J; Grajkowska, Wieslawa A; Gupta, Nalin; Hauser, Peter; Jabado, Nada; Vasiljevic, Alexandre; Jung, Shin; Kim, Seung-Ki; Klekner, Almos; Kumabe, Toshihiro; Lach, Boleslaw; Leonard, Jeffrey R; Liau, Linda M; Massimi, Luca; Pollack, Ian F; Ra, Young Shin; Rubin, Joshua B; Van Meir, Erwin G; Wang, Kyu-Chang; Weiss, William A; Zitterbart, Karel; Bristow, Robert G; Alman, Benjamin; Hawkins, Cynthia E; Malkin, David; Clifford, Steven C; Pfister, Stefan M; Taylor, Michael D; Tabori, Uri

2014-12-24

TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%±8.7%, respectively (p<0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%±2% vs. 57.4%±1.8% (p<0.01)). In contrast, β-catenin mutation sensitized TP53 mutant cells to radiation (p<0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%±1.5% in lithium treated cells vs. 56.6±3% (p<0.01)) accompanied by increased number of γH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%±8% for lithium treated cells vs. 27%±3% for untreated controls (p=0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.

Knockdown of long non-coding RNA TP73-AS1 inhibits osteosarcoma cell proliferation and invasion through sponging miR-142.

PubMed

Yang, Guangling; Song, Ruipeng; Wang, Limin; Wu, Xuejian

2018-07-01

Long non-coding RNA P73 antisense RNA 1 T (lncRNA TP73-AS1) has been shown to involve in the progression of numerous tumors. Nevertheless, the expression as well as the functional mechanisms of TP73-AS1 in osteosarcoma (OS) are still largely unknown. This study aimed to explore the roles and underlying mechanism of TP73-AS1 in OS progression. In thye present study, TP73-AS1 expression was significantly increased in OS tissues and cell lines. High TP73-AS1 expression was associated with poor overall survival of OS patients. TP73-AS1 knockdown suppressed OS cells proliferation and invasion in vitro as well as tumor growth in vivo. Furthermore, we identified that miR-142 could act as a direct target for TP73-AS1 and miR-142 inhibition reversed the suppression of OS cells proliferation and invasion induced by TP73-AS1 knockdown. In addition, we showed that TP73-AS1 could function as a sponge of miR-142 to positively regulate Rac1 in OS cells. Thus, our data suggested that TP73-AS1 served as an oncogenic lncRNA in OS progression, and could be regarded as an efficient therapeutic target in the treatment of OS. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Probing the Carbon-Hydrogen Activation of Alkanes Following Photolysis of Tp'Rh(CNR)(carbodiimide): A Computational and Time-Resolved Infrared Spectroscopic Study.

PubMed

Guan, Jia; Wriglesworth, Alisdair; Sun, Xue Zhong; Brothers, Edward N; Zarić, Snežana D; Evans, Meagan E; Jones, William D; Towrie, Michael; Hall, Michael B; George, Michael W

2018-02-07

Carbon-hydrogen bond activation of alkanes by Tp'Rh(CNR) (Tp' = Tp = trispyrazolylborate or Tp* = tris(3,5-dimethylpyrazolyl)borate) were followed by time-resolved infrared spectroscopy (TRIR) in the υ(CNR) and υ(B-H) spectral regions on Tp*Rh(CNCH 2 CMe 3 ), and their reaction mechanisms were modeled by density functional theory (DFT) on TpRh(CNMe). The major intermediate species were: κ 3 -η 1 -alkane complex (1); κ 2 -η 2 -alkane complex (2); and κ 3 -alkyl hydride (3). Calculations predict that the barrier between 1 and 2 arises from a triplet-singlet crossing and intermediate 2 proceeds over the rate-determining C-H activation barrier to give the final product 3. The activation lifetimes measured for the Tp*Rh(CNR) and Tp*Rh(CO) fragments with n-heptane and four cycloalkanes (C 5 H 10 , C 6 H 12 , C 7 H 14 , and C 8 H 16 ) increase with alkanes size and show a dramatic increase between C 6 H 12 and C 7 H 14 . A similar step-like behavior was observed previously with CpRh(CO) and Cp*Rh(CO) fragments and is attributed to the wider difference in C-H bonds that appear at C 7 H 14 . However, Tp'Rh(CNR) and Tp'Rh(CO) fragments have much longer absolute lifetimes compared to those of CpRh(CO) and Cp*Rh(CO) fragments, because the reduced electron density in dechelated κ 2 -η 2 -alkane Tp' complexes stabilizes the d 8 Rh(I) in a square-planar geometry and weakens the metal's ability for oxidative addition of the C-H bond. Further, the Tp'Rh(CNR) fragment has significantly slower rates of C-H activation in comparison to the Tp'Rh(CO) fragment for the larger cycloalkanes, because the steric bulk of the neopentyl isocyanide ligand hinders the rechelation in κ 2 -Tp'Rh(CNR)(cycloalkane) species and results in the C-H activation without the assistance of the rechelation.

Mononuclear Sulfido-Tungsten(V) Complexes: Completing the Tp*MEXY (M = Mo, W; E = O, S) Series.

PubMed

Sproules, Stephen; Eagle, Aston A; George, Graham N; White, Jonathan M; Young, Charles G

2017-05-01

Orange Tp*WSCl 2 has been synthesized from the reactions of Tp*WOCl 2 with boron sulfide in refluxing toluene or Tp*WS 2 Cl with PPh 3 in dichloromethane at room temperature. Mononuclear sulfido-tungsten(V) complexes, Tp*WSXY {X = Y = Cl, OPh, SPh, SePh; X = Cl, Y = OPh; XY = toluene-3,4-dithiolate (tdt), quinoxaline-2,3-dithiolate (qdt); and Tp* = hydrotris(3,5-dimethylpyrazol-1-yl)borate} were prepared by metathesis of Tp*WSCl 2 with the respective alkali metal salt of X - /XY 2- , or [NHEt 3 ] 2 (qdt). The complexes were characterized by microanalysis, mass spectrometry, electrochemistry, and infrared (IR), electron paramagnetic resonance (EPR) and electronic absorption spectroscopies. The molecular structures of Tp*WS(OPh) 2 , Tp*WS(SePh) 2 , and Tp*WS(tdt) have been determined by X-ray crystallography. The six-coordinate, distorted-octahedral W centers are coordinated by terminal sulfido (W≡S = 2.128(2) - 2.161(1) Å), terdentate facial Tp*, and monodentate/bidentate O/S/Se-donor ligands. The sulfido-W(V) complexes are characterized by lower energy electronic transitions, smaller g iso , and larger A iso ( 183 W) values, and more positive reduction potentials compared with their oxo-W(V) counterparts. This series has been probed by sulfur K-edge X-ray absorption spectroscopy (XAS), the spectra being assigned by comparison to Tp*WOXY (X = Y = SPh; XY = tdt, qdt) and time-dependent density functional theoretical (TD-DFT) calculations. This study provides insight into the electronic nature and chemistry of the catalytically and biologically important sulfido-W unit.

UPLC/ESI-QTOF-MS-based metabolomics survey on the toxicity of triptolide and detoxication of licorice.

PubMed

Wang, Zhuo; Liu, Jian-Qun; Xu, Jin-Di; Zhu, He; Kong, Ming; Zhang, Guo-Hua; Duan, Su-Min; Li, Xiu-Yang; Li, Guang-Fu; Liu, Li-Fang; Li, Song-Lin

2017-06-01

Triptolide (TP) from Tripterygium wilfordii has been demonstrated to possess anti-inflammatory, immunosuppressive, and anticancer activities. TP is specially used for the treatment of awkward rheumatoid arthritis, but its clinical application is confined by intense side effects. It is reported that licorice can obviously reduce the toxicity of TP, but the detailed mechanisms involved have not been comprehensively investigated. The current study aimed to explore metabolomics characteristics of the toxic reaction induced by TP and the intervention effect of licorice water extraction (LWE) against such toxicity. Obtained urine samples from control, TP and TP + LWE treated rats were analyzed by UPLC/ESI-QTOF-MS. The metabolic profiles of the control and the TP group were well differentiated by the principal component analysis and orthogonal partial least squares-discriminant analysis. The toxicity of TP was demonstrated to be evolving along with the exposure time of TP. Eight potential biomarkers related to TP toxicity were successfully identified in urine samples. Furthermore, LWE treatment could attenuate the change in six of the eight identified biomarkers. Functional pathway analysis revealed that the alterations in these metabolites were associated with tryptophan, pantothenic acid, and porphyrin metabolism. Therefore, it was concluded that LWE demonstrated interventional effects on TP toxicity through regulation of tryptophan, pantothenic acid, and porphyrin metabolism pathways, which provided novel insights into the possible mechanisms of TP toxicity as well as the potential therapeutic effects of LWE against such toxicity. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Characterizing genomic differences of human cancer stratified by the TP53 mutation status.

PubMed

Wang, Mengyao; Yang, Chao; Zhang, Xiuqing; Li, Xiangchun

2018-06-01

The key roles of the TP53 mutation in cancer have been well established. TP53 is the most frequently mutated gene, and its inactivation is widespread among human cancer types. However, the landscape of genomic alterations in human cancers stratified by the TP53 mutation has not yet been described. We obtained somatic mutation and copy number change data of 6551 regular-mutated samples from the Cancer Genome Atlas (TCGA) and compared significantly mutated genes (SMGs), copy number alterations, mutational signatures and mutational strand asymmetries between cancer samples with and without the TP53 mutation. We identified 126 SMGs, 30 of which were statistically significant in both the TP53 mutant and wild-type groups. Several SMGs, such as VHL, SMAD4 and PTEN, showed a mutation bias towards the TP53 wild-type group, whereas ATRX, IDH1 and RB1 were more prevalent in the TP53 mutant group. Five mutational signatures were extracted from the combined TCGA dataset on which mutational asymmetry analysis was performed, revealing that the TP53 mutant group exhibited substantially greater replication and transcription biases. Furthermore, we found that alterations of multiple genes in a merged mutually exclusive network composed of BRAF, EGFR, PAK1, PIK3CA, PTEN, APC and TERT were related to shortened survival in the TP53 wild-type group. In summary, we characterized the genomic differences and similarities underlying human cancers stratified by the TP53 mutation and identified multi-gene alterations of a merged mutually exclusive network to be a poor prognostic factor for the TP53 wild-type group.

Occurrence of phosphorus, iron, aluminum, silica, and calcium in a eutrophic lake during algae bloom sedimentation.

PubMed

Li, Guolian; Xie, Fazhi; Zhang, Jin; Wang, Jingrou; Yang, Ying; Sun, Ruoru

2016-09-01

Phosphorus (P) in a water body is mainly controlled by the interaction between surface sediment and the overlying water column after the complete control of external pollution. Significant enhancement of P in a water body would cause eutrophication of lakes. Thus, a better understanding is needed of the occurrences of P between the sediment and water column in eutrophic lakes. Here, we measured total phosphorus (TP) and major elements (Fe, Al, Ca, Mn, Si) in the water column, and total nitrogen, organic matter, TP and major oxides (Fe 2 O 3 , Al 2 O 3 , CaO, SiO 2 ) in surface sediment of Chaohu Lake, a continuously eutrophic lake. The results showed that the rank of TP levels was western lake > eastern lake > southern lake. There were significantly positive correlations between TP (including water TP and sedimentary TP) and Fe, Al, Mn, while the correlation coefficients between water TP and sedimentary TP were -0.43, -0.41 and 0.18 for the western, eastern and southern lake respectively. The negative and significant correlations of water TP and sedimentary TP may indicate that the risk of sedimentary P release was great in the western and eastern lake during algae bloom sedimentation, while the southern lake showed weak P exchange between the sediment and water column.

Acute effects of Red Bull energy drink on ventricular repolarization in healthy young volunteers: a prospective study

PubMed Central

Elitok, Ali; Öz, Fahrettin; Panc, Cafer; Sarıkaya, Remzi; Sezikli, Selim; Pala, Yasin; Bugan, Övgü Sinem; Ateş, Müge; Parıldar, Hilal; Ayaz, Mustafa Buğra; Atıcı, Adem; Oflaz, Hüseyin

2016-01-01

Objective: Energy drinks (EDs) are widely consumed products of the beverage industry and are often chosen by teenagers and young adults. Several adverse cardiovascular events and malignant cardiac arrhythmias following consumption of EDs have been reported in the literature. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the dispersion of repolarization and that an increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. This study investigated the acute effects of Red Bull ED on ventricular repolarization as assessed by the Tp-e interval and Tp-e/QT ratio. Methods: A prospective, open-label study design was used. After an 8-h fast, 50 young, healthy subjects consumed 355 mL of Red Bull ED. The Tp-e interval, Tp-e/QTc ratio, and several other electrocardiographic parameters were measured at baseline and 2 h after ingestion of Red Bull ED. Results: No significant changes in the Tp-e interval or Tp-e/QTc ratio were observed with Red Bull ED consumption. Red Bull ED consumption led to increases in both systolic and diastolic blood pressures, which were associated with an increased heart rate. Conclusion: Although ingestion of Red Bull ED increases the heart rate and diastolic and systolic blood pressures, it does not cause alterations in ventricular repolarization as assessed by the Tp-e interval and Tp-e/QTc ratio. PMID:25868042

Acute effects of Red Bull energy drink on ventricular repolarization in healthy young volunteers: a prospective study.

PubMed

Elitok, Ali; Öz, Fahrettin; Panc, Cafer; Sarıkaya, Remzi; Sezikli, Selim; Pala, Yasin; Bugan, Övgü Sinem; Ateş, Müge; Parıldar, Hilal; Ayaz, Mustafa Buğra; Atıcı, Adem; Oflaz, Hüseyin

2015-11-01

Energy drinks (EDs) are widely consumed products of the beverage industry and are often chosen by teenagers and young adults. Several adverse cardiovascular events and malignant cardiac arrhythmias following consumption of EDs have been reported in the literature. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the dispersion of repolarization and that an increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. This study investigated the acute effects of Red Bull ED on ventricular repolarization as assessed by the Tp-e interval and Tp-e/QT ratio. A prospective, open-label study design was used. After an 8-h fast, 50 young, healthy subjects consumed 355 mL of Red Bull ED. The Tp-e interval, Tp-e/QTc ratio, and several other electrocardiographic parameters were measured at baseline and 2 h after ingestion of Red Bull ED. No significant changes in the Tp-e interval or Tp-e/QTc ratio were observed with Red Bull ED consumption. Red Bull ED consumption led to increases in both systolic and diastolic blood pressures, which were associated with an increased heart rate. Although ingestion of Red Bull ED increases the heart rate and diastolic and systolic blood pressures, it does not cause alterations in ventricular repolarization as assessed by the Tp-e interval and Tp-e/QTc ratio.

Roles of tropical SST patterns during two types of ENSO in modulating wintertime rainfall over southern China

NASA Astrophysics Data System (ADS)

Xu, Kang; Huang, Qing-Lan; Tam, Chi-Yung; Wang, Weiqiang; Chen, Sheng; Zhu, Congwen

2018-03-01

The impacts of the eastern-Pacific (EP) and central-Pacific (CP) El Niño-Southern Oscillation (ENSO) on the southern China wintertime rainfall (SCWR) have been investigated. Results show that wintertime rainfall over most stations in southern China is enhanced (suppressed) during the EP (CP) El Niño, which are attributed to different atmospheric responses in the western North Pacific (WNP) and South China Sea (SCS) during two types of ENSO. When EP El Niño occurs, an anomalous low-level anticyclone is present over WNP/the Philippines region, resulting in stronger-than-normal southwesterlies over SCS. Such a wind branch acts to suppress East Asian winter monsoon (EAWM) and enhance moisture supply, implying surplus SCWR. During CP El Niño, however, anomalous sinking and low-level anticyclonic flow are found to cover a broad region in SCS. These circulation features are associated with moisture divergence over the northern part of SCS and suppressed SCWR. General circulation model experiments have also been conducted to study influence of various tropical sea surface temperature (SST) patterns on the EAWM atmospheric circulation. For EP El Niño, formation of anomalous low-level WNP anticyclone is jointly attributed to positive/negative SST anomalies (SSTA) over the central-to-eastern/ western equatorial Pacific. However, both positive and negative CP Niño-related-SSTA, located respectively over the central Pacific and WNP/SCS, offset each other and contribute a weak but broad-scale anticyclone centered at SCS. These results suggest that, besides the vital role of SST warming, SST cooling over SCS/WNP during two types of El Niño should be considered carefully for understanding the El Niño-EAWM relationship.

Beta-trace protein in ascites and pleural effusions: limits of CSF leakage detection.

PubMed

Dietzel, Joanna; Krebs, Alexander; Böttcher, Dominique; Sieb, Manuela; Glocker, Michael O; Lüdemann, Jan; Roser, Markus; Dressel, Alexander

2012-06-10

Rhino- and/or otoliquorrhea can be diagnosed by detecting beta-trace protein (β-TP) in nasal or ear secretions, as β-TP is found in high concentrations in cerebrospinal fluid (CSF) but not in serum. CSF fistulae following trauma or surgery can also occur at other anatomical sites, resulting in CSF leakage into the thoracic and abdominal cavities. By analogy, determination of ß-TP has also been used to diagnose CSF admixture in pleural effusions and ascites. However, no systematic study has yet evaluated the concentrations of β-TP in such fluids in the absence of CSF. To determine the validity of β-TP determination as a marker for the presence of CSF, we investigated β-TP concentrations in pleural effusions and ascites without CSF admixture. Patients from whom samples of ascites or pleural effusion and a paired plasma sample were available were investigated. One hundred sixty-four patients were prospectively recruited. ß-TP concentrations were determined by nephelometry. Mass spectrometric proteome analysis confirmed the presence of ß-TP in the samples. Median β-TP concentrations detected in ascites and pleural effusions (range, 0.014-26.5 mg/L, median 2.29 mg/L) exceeded the corresponding plasma concentrations 2.6-fold. According to cutoffs published to diagnose rhino- and otoliquorrhea, between 6.1% and 95.7% of the specimens would have been erroneously rated CSF-positive. Protein analysis confirmed the presence of β-TP in pleural effusion and ascites. Ascites and pleural effusion contain high concentrations of β-TP that exceed the levels in corresponding plasma. Therefore, β-TP is not a specific marker for the presence of CSF in these fluids.

Confocal raman microspectroscopy and imaging study of theraphthal in living cancer cells.

PubMed Central

Feofanov, A V; Grichine, A I; Shitova, L A; Karmakova, T A; Yakubovskaya, R I; Egret-Charlier, M; Vigny, P

2000-01-01

Binary systems combining a transition metal complex and ascorbate have been proposed recently for catalytic therapy of malignant tumors. The killing effect on tumor cells is achieved by production of free radicals in the course of accelerated oxidation of ascorbate by dioxygen in the presence of transition metal complexes. Further progress in the development of binary catalytic systems (BCSs) requires a special method for their investigation in cells and tissues, because neither component of BCSs fluoresces. Here a resonance Raman confocal spectral imaging (RR CSI) technique was introduced as a unique approach to monitor quantitatively the transition metal complexes within living cells. Intracellular accumulation, localization, and retention of theraphthal (TP), a catalyst of the advanced TP/ascorbate BCS, were investigated in A549 cells with the RR CSI technique. The cellular analysis was complemented with the detailed study of molecular interactions of TP in solution and environmental factors affecting the RR spectrum of TP. TP does not penetrate into membranes, it binds very weakly to DNA and RNA, but it readily forms complexes with proteins. Binding with Ca(2+) cations and decreasing pH below 6 induce aggregation of TP. By analyzing RR spectra recorded from every point within a TP-treated cell, three states of the agent were discriminated, namely, monomeric TP in polar environment, TP bound to proteins, and aggregated TP. Their cytoplasmic and nuclear distributions were mapped at different stages of uptake and efflux. By introducing organelle-selective fluorescent probes into drug-treated cells and measuring intracellular localization of both the probe and the drug, compartmentation of TP was revealed. Cell growth suppression by the TP/ascorbate system was measured, and probable molecular and organelle targets of radical damage were characterized. PMID:10620313

Evaluation of Tp-e interval and Tp-e/QT ratio in patients with non-dipper hypertension.

PubMed

Demir, Mehmet; Uyan, Umut

2014-01-01

Non-dipper hypertension is associated with increased cardiovascular morbidity and mortality. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the transmural dispersion of repolarization and that increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate ventricular repolarization by using Tp-e interval and Tp-e/QT ratio in patients with non-dipper hypertension. This study included 80 hypertensive patients. Hypertensive patients were divided into two groups: 50 dipper patients (29 male, mean age 51.5 ± 8 years) and 30 non-dipper patients (17 male, mean age 50.6 ± 5.4 years). Tp-e interval and Tp-e/QT ratio were measured from the 12-lead electrocardiogram. These parameters were compared between groups. No statistically significant difference was found between two groups in terms of basic characteristics. In electrocardiographic parameters analysis, QT dispersion (QTd) and corrected QTd were significantly increased in non-dipper patients compared to the dippers (39.4 ± 11.5 versus 27.3 ± 7.5 ms and 37.5 ± 9.5 versus 29.2 ± 6.5 ms, p = 0.001 and p = 0.01, respectively). Tp-e interval and Tp-e/QT ratio were also significantly higher in non-dipper patients (97.5 ± 11.2 versus 84.2 ± 8.3 ms and 0.23 ± 0.02 versus 0.17 ± 0.02, all p value <0.001). Our study revealed that QTd, Tp-e interval and Tp-e/QT ratio are prolonged in patients with non-dipper hypertension.

Evaluation of Tp-e interval and Tp-e/QT ratio in patients with rheumatoid arthritis.

PubMed

Acar, Gu Rkan; Akkoyun, Murat; Nacar, Alper Bugra; Dirnak, Imran; Yıldırım Çetin, Gözde; Nur Yıldırım, Makbule; Zencir, Cemil; Karaman, Kayıhan; Cetin, Mustafa; Sayarlıoğlu, Mehmet

2014-01-01

Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the transmural dispersion of repolarization and that increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate ventricular repolarization by using the Tp-e interval and Tp-e/QT ratio in patients with rheumatoid arthritis (RA), and to assess the relation with inflammation. Ninety-six patients (72 females, 24 males; mean age 43.8±11.8 years) with RA and 50 controls (35 females, 15 males; mean age 44.2±11.1 years) were included. From the 12-lead electrocardiogram, Tp-e interval and Tp-e/QT ratio were measured. Blood samples were taken for erythrocyte sedimentation rate (ESR) and plasma levels of C-reactive protein (CRP). These parameters were compared between groups. The relationship between ventricular repolarization and inflammation was assessed by Pearson correlation coefficients. Tp-e interval and Tp-e/QT ratio were increased in RA patients compared to the controls (72.6±8.2 vs 66.4±8.5 ms, 0.20±0.02 vs 0.18±0.02; p<0.001 and p<0.001, respectively). The Tp-e interval was significantly correlated with CRP, ESR, and disease activity score (DAS-28) (r=0.56, p<0.001, r=0.57, p<0.001, and r=0.29, p=0.02, respectively). The Tp-e/QT ratio was also correlated with CRP, ESR, and DAS-28 score (r=0.43, p<0.001, r=0.53, p<0.001, and r=0.25, p=0.03, respectively). In RA patients, the increased frequency of ventricular arrhythmias may be explained by increased indexes of ventricular repolarization and their relationship with inflammation.

TP53 Germline Variations Influence the Predisposition and Prognosis of B-Cell Acute Lymphoblastic Leukemia in Children

PubMed Central

Qian, Maoxiang; Cao, Xueyuan; Devidas, Meenakshi; Yang, Wenjian; Cheng, Cheng; Dai, Yunfeng; Carroll, Andrew; Heerema, Nyla A.; Zhang, Hui; Moriyama, Takaya; Gastier-Foster, Julie M.; Xu, Heng; Raetz, Elizabeth; Larsen, Eric; Winick, Naomi; Bowman, W. Paul; Martin, Paul L.; Mardis, Elaine R.; Fulton, Robert; Zambetti, Gerard; Borowitz, Michael; Wood, Brent; Nichols, Kim E.; Carroll, William L.; Pui, Ching-Hon; Mullighan, Charles G.; Evans, William E.; Hunger, Stephen P.; Relling, Mary V.; Loh, Mignon L.

2018-01-01

Purpose Germline TP53 variation is the genetic basis of Li-Fraumeni syndrome, a highly penetrant cancer predisposition condition. Recent reports of germline TP53 variants in childhood hypodiploid acute lymphoblastic leukemia (ALL) suggest that this type of leukemia is another manifestation of Li-Fraumeni syndrome; however, the pattern, prevalence, and clinical relevance of TP53 variants in childhood ALL remain unknown. Patients and Methods Targeted sequencing of TP53 coding regions was performed in 3,801 children from the Children’s Oncology Group frontline ALL clinical trials, AALL0232 and P9900. TP53 variant pathogenicity was evaluated according to experimentally determined transcriptional activity, in silico prediction of damaging effects, and prevalence in non-ALL control populations. TP53 variants were analyzed for their association with ALL presenting features and treatment outcomes. Results We identified 49 unique nonsilent rare TP53 coding variants in 77 (2.0%) of 3,801 patients sequenced, of which 22 variants were classified as pathogenic. TP53 pathogenic variants were significantly over-represented in ALL compared with non-ALL controls (odds ratio, 5.2; P < .001). Children with TP53 pathogenic variants were significantly older at ALL diagnosis (median age, 15.5 years v 7.3 years; P < .001) and were more likely to have hypodiploid ALL (65.4% v 1.2%; P < .001). Carrying germline TP53 pathogenic variants was associated with inferior event-free survival and overall survival (hazard ratio, 4.2 and 3.9; P < .001 and .001, respectively). In particular, children with TP53 pathogenic variants were at a dramatically higher risk of second cancers than those without pathogenic variants, with 5-year cumulative incidence of 25.1% and 0.7% (P < .001), respectively. Conclusion Loss-of-function germline TP53 variants predispose children to ALL and to adverse treatment outcomes with ALL therapy, particularly the risk of second malignant neoplasms. PMID:29300620

Evaluation of FlaB1, FlaB2, FlaB3, and Tp0463 of Treponema pallidum for serodiagnosis of syphilis.

PubMed

Jiang, Chuanhao; Xiao, Jinhong; Xie, Yafeng; Xiao, Yongjian; Wang, Chuan; Kuang, Xingxing; Xu, Man; Li, Ranhui; Zeng, Tiebing; Liu, Shuanquan; Yu, Jian; Zhao, Feijun; Wu, Yimou

2016-02-01

Syphilis is a multistage disease caused by the invasive spirochete Treponema pallidum subsp. pallidum, and accurate diagnosis is important for the prevention and treatment of syphilis. Here, to identify appropriate diagnostic antigens for serodiagnosis of syphilis, 6 recombinant proteins were expressed in Escherichia coli and purified, including flagellins (FlaB1 [Tp0868], FlaB2 [Tp0792], and FlaB3 [Tp0870]), Tp0463, Tp0751, and Tp1038. The sensitivities were determined by screening sera from individuals with primary (n=82), secondary (n=115), latent (n=105), and congenital (n=65) syphilis. The specificities were determined by screening sera from uninfected controls (n=30) and potentially cross-reactive infections including Lyme disease (n=30), leptospirosis (n=5), and hepatitis B (n=30). Our data showed that FlaB1, FlaB2, FlaB3, Tp0463, and Tp1038 exhibited higher overall sensitivities and specificities for detecting IgG antibody, with 95.4% and 98.9%, 92.6% and 95.8%, 95.1% and 95.8%, 92.6% and 97.9%, and 95.9% and 98.9%, respectively. In contrast, Tp0751 demonstrated only an overall sensitivity of 39.2%. For comparison, the sensitivity and specificity of Architect Syphilis TP were determined to be 98.1% and 93.7%, respectively. In addition, FlaB1, FlaB2, FlaB3, and Tp0463 demonstrated excellent performance for detecting IgM antibody in primary and congenital syphilis, with sensitivities of 76.8% and 83.1%, 72.0% and 87.7%, 74.4% and 89.2%, and 64.6% and 75.3%, respectively. These results indicate that FlaB1, FlaB2, FlaB3, and Tp0463 could be as novel diagnostic candidates for serodiagnosis of syphilis. Copyright © 2016 Elsevier Inc. All rights reserved.

RITA displays anti-tumor activity in medulloblastomas independent of TP53 status.

PubMed

Gottlieb, Aline; Althoff, Kristina; Grunewald, Laura; Thor, Theresa; Odersky, Andrea; Schulte, Marc; Deubzer, Hedwig E; Heukamp, Lukas; Eggert, Angelika; Schramm, Alexander; Schulte, Johannes H; Künkele, Annette

2017-04-25

Current therapy of medulloblastoma, the most common malignant brain tumor of childhood, achieves 40-70% survival. Secondary chemotherapy resistance contributes to treatment failure, where TP53 pathway dysfunction plays a key role. MDM2 interaction with TP53 leads to its degradation. Reactivating TP53 functionality using small-molecule inhibitors, such as RITA, to disrupt TP53-MDM2 binding may have therapeutic potential. We show here that RITA decreased viability of all 4 analyzed medulloblastoma cell lines, regardless of TP53 functional status. The decrease in cell viability was accompanied in 3 of the 4 medulloblastoma cell lines by accumulation of TP53 protein in the cells and increased CDKN1A expression. RITA treatment in mouse models inhibited medulloblastoma xenograft tumor growth. These data demonstrate that RITA treatment reduces medulloblastoma cell viability in both in vitro and in vivo models, and acts independently of cellular TP53 status, identifying RITA as a potential therapeutic agent to treat medulloblastoma.

RITA displays anti-tumor activity in medulloblastomas independent of TP53 status

PubMed Central

Gottlieb, Aline; Althoff, Kristina; Grunewald, Laura; Thor, Theresa; Odersky, Andrea; Schulte, Marc; Deubzer, Hedwig E.; Heukamp, Lukas; Eggert, Angelika; Schramm, Alexander; Schulte, Johannes H.; Künkele, Annette

2017-01-01

Current therapy of medulloblastoma, the most common malignant brain tumor of childhood, achieves 40–70% survival. Secondary chemotherapy resistance contributes to treatment failure, where TP53 pathway dysfunction plays a key role. MDM2 interaction with TP53 leads to its degradation. Reactivating TP53 functionality using small-molecule inhibitors, such as RITA, to disrupt TP53-MDM2 binding may have therapeutic potential. We show here that RITA decreased viability of all 4 analyzed medulloblastoma cell lines, regardless of TP53 functional status. The decrease in cell viability was accompanied in 3 of the 4 medulloblastoma cell lines by accumulation of TP53 protein in the cells and increased CDKN1A expression. RITA treatment in mouse models inhibited medulloblastoma xenograft tumor growth. These data demonstrate that RITA treatment reduces medulloblastoma cell viability in both in vitro and in vivo models, and acts independently of cellular TP53 status, identifying RITA as a potential therapeutic agent to treat medulloblastoma. PMID:28427187

Involvement of Cot/Tp12 in bone loss during periodontitis.

PubMed

Ohnishi, T; Okamoto, A; Kakimoto, K; Bandow, K; Chiba, N; Matsuguchi, T

2010-02-01

Periodontitis causes resorption of alveolar bone, in which RANKL induces osteoclastogenesis. The binding of lipopolysaccharide to Toll-like receptors causes phosphorylation of Cot/Tp12 to activate the MAPK cascade. Previous in vitro studies showed that Cot/Tp12 was essential for the induction of RANKL expression by lipopolysaccharide. In this study, we examined whether Cot/Tp12 deficiency reduced the progression of alveolar bone loss and osteoclastogenesis during experimental periodontitis. We found that the extent of alveolar bone loss and osteoclastogenesis induced by ligature-induced periodontitis was decreased in Cot/Tp12-deficient mice. In addition, reduction of RANKL expression was observed in periodontal tissues of Cot/Tp12-deficient mice with experimental periodontitis. Furthermore, we found that Cot/Tp12 was involved in the induction of TNF-alpha mRNA expression in gingiva of mice with experimental periodontitis. Our observations suggested that Cot/Tp12 is essential for the progression of alveolar bone loss and osteoclastogenesis in periodontal tissue during experimental periodontitis mediated through increased RANKL expression.

TpUB05, a Homologue of the Immunodominant Plasmodium falciparum Protein UB05, Is a Marker of Protective Immune Responses in Cattle Experimentally Vaccinated against East Coast Fever

PubMed Central

Dinga, Jerome Nyhalah; Wamalwa, Mark; Njimoh, Dieudonné Lemuh; Njahira, Moses N.; Djikeng, Appolinaire; Skilton, Rob; Titanji, Vincent Pryde Kehdingha; Pellé, Roger

2015-01-01

Introduction East Coast fever, a devastating disease of cattle, can be controlled partially by vaccination with live T. parva sporozoites. The antigens responsible for conferring immunity are not fully characterized. Recently it was shown that the P. falciparum immunodominant protein UB05 is highly conserved in T. parva, the causative agent of East Coast fever. The aim of the present investigation was to determine the role of the homologue TpUB05 in protective immunity to East Coast fever. Methods The cloning, sequencing and expression of TpUB05 were done according to standard protocols. Bioinformatics analysis of TpUB05 gene was carried out using algorithms found in the public domain. Polyclonal antiserum against recombinant TpUB05 were raised in rabbits and used for further analysis by Western blotting, ELISA, immunolocalization and in vitro infection neutralization assay. The ability of recombinant TpUB05 (r-TpUB05) to stimulate bovine PBMCs ex-vivo to produce IFN-γ or to proliferate was tested using ELISpot and [3H]-thymidine incorporation assays, respectively. Results All the 20 cattle immunised by the infection and treatment method (ITM) developed significantly higher levels of TpUB05 specific antibodies (p<0.0001) compared to the non-vaccinated ones. Similarly, r-TpUB05 highly stimulated bovine PMBCs from 8/12 (67%) of ITM-immunized cattle tested to produce IFN-γ and proliferate (p< 0.029) as compared to the 04 naїve cattle included as controls. Polyclonal TpUB05 antiserum raised against r-TpUB05 also marginally inhibited infection (p < 0.046) of bovine PBMCs by T. parva sporozoites. In further experiments RT-PCR showed that the TpUB05 gene is expressed by the parasite. This was confirmed by immunolocalization studies which revealed TpUB05 expression by schizonts and piroplasms. Bioinformatics analysis also revealed that this antigen possesses two transmembrane domains, a N-glycosylation site and several O-glycosylation sites. Conclusion It was concluded that TpUB05 is a potential marker of protective immunity in ECF worth investigating further. PMID:26053064

TpUB05, a Homologue of the Immunodominant Plasmodium falciparum Protein UB05, Is a Marker of Protective Immune Responses in Cattle Experimentally Vaccinated against East Coast Fever.

PubMed

Dinga, Jerome Nyhalah; Wamalwa, Mark; Njimoh, Dieudonné Lemuh; Njahira, Moses N; Djikeng, Appolinaire; Skilton, Rob; Titanji, Vincent Pryde Kehdingha; Pellé, Roger

2015-01-01

East Coast fever, a devastating disease of cattle, can be controlled partially by vaccination with live T. parva sporozoites. The antigens responsible for conferring immunity are not fully characterized. Recently it was shown that the P. falciparum immunodominant protein UB05 is highly conserved in T. parva, the causative agent of East Coast fever. The aim of the present investigation was to determine the role of the homologue TpUB05 in protective immunity to East Coast fever. The cloning, sequencing and expression of TpUB05 were done according to standard protocols. Bioinformatics analysis of TpUB05 gene was carried out using algorithms found in the public domain. Polyclonal antiserum against recombinant TpUB05 were raised in rabbits and used for further analysis by Western blotting, ELISA, immunolocalization and in vitro infection neutralization assay. The ability of recombinant TpUB05 (r-TpUB05) to stimulate bovine PBMCs ex-vivo to produce IFN-γ or to proliferate was tested using ELISpot and [3H]-thymidine incorporation assays, respectively. All the 20 cattle immunised by the infection and treatment method (ITM) developed significantly higher levels of TpUB05 specific antibodies (p<0.0001) compared to the non-vaccinated ones. Similarly, r-TpUB05 highly stimulated bovine PMBCs from 8/12 (67%) of ITM-immunized cattle tested to produce IFN-γ and proliferate (p< 0.029) as compared to the 04 naїve cattle included as controls. Polyclonal TpUB05 antiserum raised against r-TpUB05 also marginally inhibited infection (p < 0.046) of bovine PBMCs by T. parva sporozoites. In further experiments RT-PCR showed that the TpUB05 gene is expressed by the parasite. This was confirmed by immunolocalization studies which revealed TpUB05 expression by schizonts and piroplasms. Bioinformatics analysis also revealed that this antigen possesses two transmembrane domains, a N-glycosylation site and several O-glycosylation sites. It was concluded that TpUB05 is a potential marker of protective immunity in ECF worth investigating further.

Treponema pallidum western blot: comparison with the FTA-ABS test as a confirmatory test for syphilis.

PubMed

Backhouse, J L; Nesteroff, S I

2001-01-01

We developed a Treponema pallidum Western blot and compared the results with Treponema pallidum particle agglutination (TPPA) and fluorescent treponemal antibody absorption (FTA-ABS) tests. The Western blot was deemed reactive if the serum reacted with at least three major antigenic bands (TpN47, TpN44.5, TpN17, TpN15). The sensitivities of the Western blot, TPPA and FTA-ABS, were all 100% and the specificities of the Western blot, TPPA and FTA-ABS were 100%, 100% and 94.5% respectively. In 52 problem sera, reactive in only one treponemal test, the agreement between the Western blot and TPPA (61.5%) was significantly better than between Western blot and FTA-ABS (38.5%). The individual sensitivities and specificities of TpN47, TpN44.5, TpN17, TpN15 were 100%, 100%, 96%, 100% and 20%, 96%, 100%, 100% respectively. We conclude that the Western blot is a useful additional confirmatory test or alternative to the FTA-ABS and that a more sensitive and specific criterion for the Western blot would be reactivity with TpN15 and two of the three other major antigens.

Evaluation of a fully automated treponemal test and comparison with conventional VDRL and FTA-ABS tests.

PubMed

Park, Yongjung; Park, Younhee; Joo, Shin Young; Park, Myoung Hee; Kim, Hyon-Suk

2011-11-01

We evaluated analytic performances of an automated treponemal test and compared this test with the Venereal Disease Research Laboratory test (VDRL) and fluorescent treponemal antibody absorption test (FTA-ABS). Precision performance of the Architect Syphilis TP assay (TP; Abbott Japan, Tokyo, Japan) was assessed, and 150 serum samples were assayed with the TP before and after heat inactivation to estimate the effect of heat inactivation. A total of 616 specimens were tested with the FTA-ABS and TP, and 400 were examined with the VDRL. The TP showed good precision performance with total imprecision of less than a 10% coefficient of variation. An excellent linear relationship between results before and after heat inactivation was observed (R(2) = 0.9961). The FTA-ABS and TP agreed well with a κ coefficient of 0.981. The concordance rate between the FTA-ABS and TP was the highest (99.0%), followed by the rates between FTA-ABS and VDRL (85.0%) and between TP and VDRL (83.8%). The automated TP assay may be adequate for screening for syphilis in a large volume of samples and can be an alternative to FTA-ABS.

Synthesis, characterization, and electrochemistry of cis-oxothio- and cis-bis(thio)tungsten(VI) complexes of hydrotris(3,5-dimethylpyrazol-1-yl)borate.

PubMed

Eagle, A A; Tiekink, E R; George, G N; Young, C G

2001-08-27

The complexes TpWO2X react with sulfiding agents such as B2S3 or P4S10 to give the oxothio- and bis(thio)tungsten(VI) complexes TpWOSX (X = Cl(-)) and TpWS2X [X = Cl(-), S2PPh2(-); Tp = hydrotris(3,5-dimethylpyrazol-1-yl)borate]. The reaction of TpWS2Cl with (i) PPh3 in pyridine and (ii) dimethyl sulfoxide affords TpWOSCl in good overall yield. The chloro complexes undergo metathesis with alkali metal salts to yield species of the type TpWOSX and TpWS2X [X = OPh(-), SPh(-), SePh(-), (-)-mentholate]. The diamagnetic complexes exhibit NMR spectra indicative of C(1) (TpWOSX) or C(s) (TpWS2X) symmetry and IR spectra consistent with terminal oxo and thio ligation (nu(W=O), 940-925 cm(-1); nu(W=S) or nu(WS2), 495-475 cm(-1)). Crystals of (R,S)-TpWOS[(-)-mentholate] are monoclinic, space group P2(1), with a = 11.983(2) A, b = 18.100(3) A, c = 13.859(3) A, beta = 91.60(2) degrees, V = 3004.6(8) A(3), and Z = 4. Crystals of TpWS2(OPh)-CH2Cl2 are orthorhombic, space group Pbca, with a = 16.961(4) A, b = 33.098(7) A, c = 9.555(2) A, V = 5364(2) A(3), and Z = 8. The mononuclear, distorted-octahedral tungsten centers are coordinated by a tridentate Tp ligand, an alkoxy or aryloxy ligand, and two terminal chalcogenide ligands. The average W=O and W=S distances are 1.726(7) and 2.125(2) A, respectively, and the O=W=S and S=W=S angles 102.9(3) and 102.9(1) degrees, respectively. The tungsten and sulfur X-ray absorption spectra of TpWOSCl and TpWS2Cl are consistent with the presence of terminal pi-bonded thio ligands in both complexes. The thio complexes generally undergo a reversible one-electron reduction at potentials significantly more positive than their oxo analogues. The chemical, spectroscopic, and electrochemical properties of the complexes are heavily influenced by the presence of W=S pi frontier orbitals.

Redox interplay of oxo-thio-tungsten centers with sulfur-donor co-ligands.

PubMed

Thomas, Simon; Eagle, Aston A; Sproules, Stephen A; Hill, Jason P; White, Jonathan M; Tiekink, Edward R T; George, Graham N; Young, Charles G

2003-09-22

The oxo-thio-W(VI) complexes TpWOS(S(2)PR(2)-S) and TpWOS(pyS-S) (Tp = hydrotris(3,5-dimethylpyrazol-1-yl)borate, R = OEt, Ph; pyS = pyridine-2-thiolate) have been prepared and characterized by microanalytical, spectroscopic, and structural techniques. Crystals of the 1,2-dichloroethane hemisolvate of TpWOS(S(2)PPh(2)-S) belong to the triclinic space group Ponemacr; with a = 10.732(6) A, b = 16.91(1) A, c = 10.021(4) A, alpha = 104.40(4) degrees, beta = 107.52(3) degrees, gamma = 96.09(5) degrees, V = 1647(1) A(3) for Z = 2. The complex exhibits a distorted octahedral structure featuring a facial tridentate Tp ligand and mutually cis terminal oxo (W-O(1) = 1.712(7) A), terminal thio (W-S(1) = 2.162(3) A), and monodentate dithiophosphinate ligands. X-ray absorption and extended X-ray absorption fine structure results support a related oxo-thio formulation for TpWOS(pyS-S). The complexes are reduced to the corresponding oxo-thio-W(V) anions, [TpWOS(S(2)PR(2)-S)](-) and [TpWOS(pyS-S)](-), which exhibit highly anisotropic EPR spectra. They are oxidized to form the EPR-active (dithio)oxo-W(V) cations, [TpWO(S(3)PR(2)-S,S')](+) and [TpWO(pyS(2)-N,S)](+) (pyS(2) = pyridine-2-dithio). Green [TpWO(pyS(2)-N,S)]BF(4), formed in the reaction of TpWOS(pyS) and NOBF(4), has been isolated and spectroscopically and structurally characterized. Crystals of [TpWO(pyS(2)-N,S)]BF(4) belong to the monoclinic space group Cc with a = 16.007(5) A, b = 14.091(4) A, c = 13.608(4) A, beta = 124.525(4) degrees, V = 2528.8(13) A(3) for Z = 4. The cation exhibits a distorted octahedral structure featuring facial tridentate Tp, terminal oxo (W-O(1) = 1.632(12) A), and bidentate pyridine-2-dithio-N,S (W-S(1) = 2.317(7) A, S(1)-S(2) = 2.037(9) A) ligands. The structures and redox behavior of the complexes are compared and contrasted with those of the related molybdenum complexes, TpMo(VI)OS(S(2)PR(2)-S) and TpMo(IV)O(pyS(2)-N,S) (Hill, J. P.; Laughlin, L. J.; Gable, R. W.; Young, C. G. Inorg. Chem. 1996, 35, 3447).

[Induction chemotherapy with docetaxel plus cisplatin (TP regimen) followed by concurrent chemoradiotherapy with TP regimen versus cisplatin in treating locally advanced nasopharyngeal carcinoma].

PubMed

Xie, Fang-Yun; Zou, Guo-Rong; Hu, Wei-Han; Qi, Shu-Nan; Peng, Miao; Li, Ji-Shi

2009-03-01

Clinical trials on docetaxel plus cisplatin (DDP) (TP regimen) in treating nasopharyngeal carcinoma (NPC) are still uncertain due to limited samples. This study was to compare the short-term efficacy and toxicity of induction chemotherapy with TP regimen followed by concurrent chemoradiotherapy with TP regimen versus DDP in treating locally advanced NPC. Fifty-seven patients with stage T3-4N2-3M0 NPC diagnosed pathologically from December 2005 to December 2006 were randomized into TP group (30 patients) and DDP group (27 patients). Both groups received TP regimen as induction chemotherapy with docetaxel (70 mg/m(2)) on Day 1 and DDP (80 mg/m(2)) on Day 2, repeating every 21 days for 2 cycles. For concurrent chemotherapy, TP group were administered docetaxel (60 mg/m(2)) on Day 1 and DDP (80 mg/m(2)) on Day 2; DDP group were administered DDP (80 mg/m(2)) on Day 1. Both schedules were repeated every 21 days for 2 cycles. Linear accelerator was used as radioactive source. Irradiation field was designed with CT-simulation and conventional fractions. The 57 patients received 111 cycles of induction chemotherapy, and 53 of them received 103 cycles of concurrent chemotherapy; four patients ceased induction chemotherapy and three ceased concurrent chemotherapy. All patients completed radiotherapy. The major toxicity of induction chemotherapy was hematologic toxicity; the main toxicities of concurrent chemoradiotherapy were hematologic toxicity and mucositis. The occurrence rates of Grade 3-4 leucopenia and Grade 3-4 neutropenia were significantly higher in TP group than in DDP groups (p <0.05). In concurrent chemoradiotherapy, the application rate of granulocyte colony stimulating factor (G-CSF) was significantly higher in TP group than in DDP group (100% vs. 72.0%, p<0.05). After concurrent chemoradiotherapy, the complete remission (CR) rates of the nasopharynx and regional lymph nodes were 93.3% and 92.9% in TP group, and were 96.3% and 91.3% in DDP group (p>0.05). The short-term efficacy of induction chemotherapy with TP regimen followed by concurrent chemoradiotherapy with TP regimen on locally advanced NPC is similar to that of TP regimen followed by concurrent chemoradiotherapy with DDP. The toxicity of the former schedule is severer than that of the latter, but it is tolerable with the use of G-CSF. The long-term efficacy of induction chemotherapy with TP regimen followed by concurrent chemoradiotherapy with TP regimen need to be further studied.

Prophylaxis of venous thromboembolism in elderly patients with multimorbidity.

PubMed

Marcucci, Maura; Iorio, Alfonso; Nobili, Alessandro; Tettamanti, Mauro; Pasina, Luca; Djade, Codjo Djignefa; Marengoni, Alessandra; Salerno, Francesco; Corrao, Salvatore; Mannucci, Pier Mannuccio

2013-09-01

Pharmacological thromboprophylaxis (TP) is known to reduce venous thromboembolism (VTE) in medical inpatients, but the criteria for risk-driven prescription, safety and impact on mortality are still debated. We analyze data on elderly patients with multimorbidities admitted in the year 2010 to the Italian internal medicine wards participating in the REPOSI registry to investigate the rate of TP during the hospital stay, and analyze the factors that are related to its prescription. Multivariate logistic regression, area under the ROC curve and CART analysis were performed to look for independent predictors of TP prescription. Association between TP and VTE, bleeding and death in hospital and during the 3-month post-discharge follow-up were explored by logistic regression and propensity score analysis. Among the 1,380 patients enrolled, 171 (15.2 %) were on TP during the hospital stay (162 on low molecular weight heparins, 9 on fondaparinux). The disability Barthel index was the main independent predictor of TP prescription. Rate of fatal and non-fatal VTE and bleeding during and after hospitalization did not differ between TP and non-TP patients. In-hospital and post-discharge mortality was significantly higher in patients on TP, that however was not an independent predictor of mortality. Among elderly medical patients there was a relatively low rate of TP, that was more frequently prescribed to patients with a higher degree of disability and who had an overall higher mortality.

Full-length mutation search of the TP53 gene in acute myeloid leukemia has increased significance as a prognostic factor.

PubMed

Terada, Kazuki; Yamaguchi, Hiroki; Ueki, Toshimitsu; Usuki, Kensuke; Kobayashi, Yutaka; Tajika, Kenji; Gomi, Seiji; Kurosawa, Saiko; Miyadera, Keiki; Tokura, Taichiro; Omori, Ikuko; Marumo, Atushi; Fujiwara, Yusuke; Yui, Shunsuke; Ryotokuji, Takeshi; Osaki, Yoshiki; Arai, Kunihito; Kitano, Tomoaki; Kosaka, Fumiko; Wakita, Satoshi; Tamai, Hayato; Fukuda, Takahiro; Inokuchi, Koiti

2018-01-01

TP53 gene abnormality has been reported to be an unfavorable prognostic factor in acute myeloid leukemia (AML). However, almost all studies of TP53 gene abnormality so far have been limited to mutation searches in the DNA binding domain. As there have been few reports examining both mutation and deletion over the full-length of the TP53 gene, the clinical characteristics of TP53 gene abnormality have not yet been clearly established. In this study, TP53 gene mutation was observed in 7.3% of the total 412 de novo AML cases (33 mutations in 30 cases), with mutation outside the DNA binding domain in eight cases (27%). TP53 gene deletion was observed in 3.1% of 358 cases. All cases had monoallelic deletion with TP53 gene mutation on the opposite allele. Multivariate analysis demonstrated that TP53 gene mutation in the DNA binding domain and outside the DNA binding domain was an independent poor prognostic factor for overall survival and relapse-free survival among the total cohort and it is also an unfavorable prognostic factor in FLT3-ITD-negative AML cases aged 70 years or below with intermediate cytogenetic prognosis. In stratified treatment, full-length search for TP53 gene mutation is therefore very important.

TP53INP2/DOR, a mediator of cell autophagy, promotes rDNA transcription via facilitating the assembly of the POLR1/RNA polymerase I preinitiation complex at rDNA promoters.

PubMed

Xu, Yinfeng; Wan, Wei; Shou, Xin; Huang, Rui; You, Zhiyuan; Shou, Yanhong; Wang, Lingling; Zhou, Tianhua; Liu, Wei

2016-07-02

Cells control their metabolism through modulating the anabolic and catabolic pathways. TP53INP2/DOR (tumor protein p53 inducible nuclear protein 2), participates in cell catabolism by serving as a promoter of autophagy. Here we uncover a novel function of TP53INP2 in protein synthesis, a major biosynthetic and energy-consuming anabolic process. TP53INP2 localizes to the nucleolus through its nucleolar localization signal (NoLS) located at the C-terminal domain. Chromatin immunoprecipitation (ChIP) assays detected an association of TP53INP2 with the ribosomal DNA (rDNA), when exclusion of TP53INP2 from the nucleolus repressed rDNA promoter activity and the production of ribosomal RNA (rRNA) and proteins. The removal of TP53INP2 also impaired the association of the POLR1/RNA polymerase I preinitiation complex (PIC) with rDNA. Further, TP53INP2 interacts directly with POLR1 PIC, and is required for the assembly of the complex. These data indicate that TP53INP2 promotes ribosome biogenesis through facilitating rRNA synthesis at the nucleolus, suggesting a dual role of TP53INP2 in cell metabolism, assisting anabolism on the nucleolus, and stimulating catabolism off the nucleolus.

Exquisite sensitivity of TP53 mutant and basal breast cancers to a dose-dense epirubicin-cyclophosphamide regimen.

PubMed

Bertheau, Philippe; Turpin, Elisabeth; Rickman, David S; Espié, Marc; de Reyniès, Aurélien; Feugeas, Jean-Paul; Plassa, Louis-François; Soliman, Hany; Varna, Mariana; de Roquancourt, Anne; Lehmann-Che, Jacqueline; Beuzard, Yves; Marty, Michel; Misset, Jean-Louis; Janin, Anne; de Thé, Hugues

2007-03-01

In breast cancers, only a minority of patients fully benefit from the different chemotherapy regimens currently in use. Identification of markers that could predict the response to a particular regimen would thus be critically important for patient care. In cell lines or animal models, tumor protein p53 (TP53) plays a critical role in modulating the response to genotoxic drugs. TP53 is activated in response to DNA damage and triggers either apoptosis or cell-cycle arrest, which have opposite effects on cell fate. Yet, studies linking TP53 status and chemotherapy response have so far failed to unambiguously establish this paradigm in patients. Breast cancers with a TP53 mutation were repeatedly shown to have a poor outcome, but whether this reflects poor response to treatment or greater intrinsic aggressiveness of the tumor is unknown. In this study we analyzed 80 noninflammatory breast cancers treated by frontline (neoadjuvant) chemotherapy. Tumor diagnoses were performed on pretreatment biopsies, and the patients then received six cycles of a dose-dense regimen of 75 mg/m(2) epirubicin and 1,200 mg/m(2) cyclophosphamide, given every 14 days. After completion of chemotherapy, all patients underwent mastectomies, thus allowing for a reliable assessment of chemotherapy response. The pretreatment biopsy samples were used to determine the TP53 status through a highly efficient yeast functional assay and to perform RNA profiling. All 15 complete responses occurred among the 28 TP53-mutant tumors. Furthermore, among the TP53-mutant tumors, nine out of ten of the highly aggressive basal subtypes (defined by basal cytokeratin [KRT] immunohistochemical staining) experienced complete pathological responses, and only TP53 status and basal subtype were independent predictors of a complete response. Expression analysis identified many mutant TP53-associated genes, including CDC20, TTK, CDKN2A, and the stem cell gene PROM1, but failed to identify a transcriptional profile associated with complete responses among TP53 mutant tumors. In patients with unresponsive tumors, mutant TP53 status predicted significantly shorter overall survival. The 15 patients with responsive TP53-mutant tumors, however, had a favorable outcome, suggesting that this chemotherapy regimen can overcome the poor prognosis generally associated with mutant TP53 status. This study demonstrates that, in noninflammatory breast cancers, TP53 status is a key predictive factor for response to this dose-dense epirubicin-cyclophosphamide regimen and further suggests that the basal subtype is exquisitely sensitive to this association. Given the well-established predictive value of complete responses for long-term survival and the poor prognosis of basal and TP53-mutant tumors treated with other regimens, this chemotherapy could be particularly suited for breast cancer patients with a mutant TP53, particularly those with basal features.

Convolutional Neural Networks as Feature Extractors for Data Scarce Visual Searches

DTIC Science & Technology

2016-09-01

50 Figure C.16 TP for the Ferrari Logo (layer=FC7). . . . . . . . . . . . . . . . 50 Figure C.17 TP for the Kia Logo (layer=FC6...51 Figure C.18 TP for the Kia Logo (layer=FC7). . . . . . . . . . . . . . . . . . 51 Figure C.19 TP for the Liege Logo (layer=FC6...represent results for test samples from the Ferrari class for k=1, k=3, and k=5. 50 Figure C.17. TP for the Kia Logo (layer=FC6). The x-axis represents

Thymidine Phosphorylase is Angiogenic and Promotes Tumor Growth

NASA Astrophysics Data System (ADS)

Moghaddam, Amir; Zhang, Hua-Tang; Fan, Tai-Ping D.; Hu, De-En; Lees, Vivien C.; Turley, Helen; Fox, Stephen B.; Gatter, Kevin C.; Harris, Adrian L.; Bicknell, Roy

1995-02-01

Platelet-derived endothelial cell growth factor was previously identified as the sole angiogenic activity present in platelets; it is now known to be thymidine phosphorylase (TP). The effect of TP on [methyl-^3H]thymidine uptake does not arise from de novo DNA synthesis and the molecule is not a growth factor. Despite this, TP is strongly angiogenic in a rat sponge and freeze-injured skin graft model. Neutralizing antibodies and site-directed mutagenesis confirmed that the enzyme activity of TP is a condition for its angiogenic activity. The level of TP was found to be elevated in human breast tumors compared to normal breast tissue (P < 0.001). Overexpression of TP in MCF-7 breast carcinoma cells had no effect on growth in vitro but markedly enhanced tumor growth in vivo. These data and the correlation of expression in tumors with malignancy identify TP as a target for antitumor strategies.

A time to be stressed? Time perspectives and cortisol dynamics among healthy adults.

PubMed

Olivera-Figueroa, Lening A; Juster, Robert-Paul; Morin-Major, Julie Katia; Marin, Marie-France; Lupien, Sonia J

2015-10-01

Perceptions of past, present, and future events may be related to stress pathophysiology. We assessed whether Time Perspective (TP) is associated with cortisol dynamics among healthy adults (N=61, Ages=18-35, M=22.9, SD=4.1) exposed to the Trier Social Stress Test (TSST). TP was measured according to two profiles: maladaptive Deviation from Balanced TP (DBTP) and adaptive Deviation from Negative TP (DNTP). Eight salivary cortisol samples were analyzed using area under the curve with respect to ground (AUCg) and to increase (AUCi). Statistic analyses involved partial correlations controlling for depressive symptoms. Results for both sexes showed that higher DBTP scores were associated with lower cortisol AUCg scores, while higher DNTP scores were associated with higher cortisol AUCg scores. These novel findings suggest that maladaptive TP profiles influence hypocortisolism, whereas adaptive TP profiles influence hypercortisolism. Thus, TP profiles may impact conditions characterized by altered cortisol concentrations. Published by Elsevier B.V.

The prevalence of transpancreatic common hepatic artery and coexisting variant anatomy.

PubMed

Ishigami, Kousei; Nishie, Akihiro; Asayama, Yoshiki; Ushijima, Yasuhiro; Takayama, Yukihisa; Okamoto, Daisuke; Fujita, Nobuhiro; Yoshizumi, Tomoharu; Harimoto, Norifumi; Ohtsuka, Takao; Nakata, Kohei; Honda, Hiroshi

2018-05-01

We studied the prevalence of the transpancreatic common hepatic artery (tp-CHA) and coexisting variant anatomy. The study group comprised 788 consecutive liver transplant donor candidates who had undergone thin-section multidetector-row computed tomography (MDCT) studies to investigate vascular anatomy. Multiplanar reformatted (MPR) images obtained from the arterial phase were retrospectively reviewed to assess the presence/absence of the tp-CHA. Five cases of tp-CHA with pancreaticobiliary tumors were also included in an investigation of the presence/absence of variant hepatic arteries, celiac stenosis, and circumportal pancreas. Three of the 788 (0.38%) donor candidates had a tp-CHA. Overall, eight tp-CHA cases were assessed for coexisting variant anatomy. Seven of these eight cases had a hepatomesenteric trunk, six had celiac stenosis, and two had a circumportal pancreas. The prevalence of the tp-CHA was 0.38% (approx. one in 260 in normal populations). A tp-CHA can commonly be associated with a hepatomesenteric trunk and celiac stenosis. A circumportal pancreas can also coexist with a tp-CHA. Clin. Anat. 31:598-604, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Association between Washing Residue on the Feet and Tinea Pedis in Diabetic Patients

PubMed Central

Takehara, Kimie; Amemiya, Ayumi; Mugita, Yuko; Tsunemi, Yuichiro; Seko, Yoko; Ohashi, Yumiko; Ueki, Kohjiro; Kadowaki, Takashi; Nagase, Takashi; Ikeda, Mari; Sanada, Hiromi

2015-01-01

Tinea pedis (TP) may lead to the development of foot ulcers in diabetic patients; thus, its prevention in diabetic patients is important. TP occurs after dermatophytes on the skin scales of TP patients attach to the feet. Therefore, it is necessary to remove the scales and dermatophytes, and this can be performed using various methods, including foot washing. This study aimed to objectively examine the association between the presence of TP and foot-washing habits. We included 33 diabetic patients, and, of these, 17 had TP. The presence of washing residue on the feet was determined by applying a fluorescent cream to the participants' feet, and images of the feet were captured under ultraviolet light before and after foot washing. Our results showed that diabetic patients with TP had higher levels of washing residue on their feet than those without TP. The importance of washing feet to prevent TP needs to be emphasized through educational programs for diabetic patients. Furthermore, the development of an effective foot-washing technique is essential. PMID:25793125

Metabolic fate of fenetylline in rat and man.

PubMed

Yoshimura, H; Yoshimitsu, T; Yamada, H; Koga, N; Oguri, K

1988-08-01

1. Metabolic fate of 7-[2-(alpha-methylphenylethylamino)ethyl]theophylline hydrochloride (fenetylline) was investigated in male Sprague-Dawley rats and three male volunteers. 2. Six metabolites were identified in the rat urine as amphetamine(AP), p-hydroxy-AP, acetylaminoethyl-theophylline(TP), aminoethyl-TP, hydroxyethyl-TP and carboxymethyl-TP by comparison of their spectral properties and h.p.l.c. and g.l.c. characteristics with those of authentic samples. All these metabolites was also detected in the urine of humans receiving fenetylline. 3. Quantification of these metabolites using h.p.l.c. and g.l.c. showed that carboxymethyl-TP, p-hydroxy-AP and acetylaminoethyl-TP were the major metabolites in 0-24 h rat urine at 13.7%, 11.2% and 9.3% of dose, respectively. In men, carboxymethyl-TP(39-43% dose) and AP(23-33% dose) were the major metabolites in 0-48 h urine. 4. These results suggest that fenetylline metabolism proceeds via oxidative cleavage at two different sites to produce aminoethyl-TP and AP, respectively. The pathway producing AP predominates, in both man and rat, but is more predominant in the former.

Rotorcraft Flight Simulation, Computer Program C81. Volume 2. User’s Manual

DTIC Science & Technology

1979-10-01

o . 7 𔄂 7 2 0 .0 0 1 1 - 2 · 2t > 1 9 1 9 3 .0 - 2 2 .9 2 3 0 .6 1 7 2 2 4 .4 0 o .e :J f6 o .o o l7 -2 o 2 1 ro 9 l 1 4 6...FT/SEC**2 2231 RT:4 2.8L0 S*STA Is CHORD ACC. FT/SEC**2 2232 RTq 29BL0 6.@STA 1o CHORD ACCa FT/SEC**2 2233 RTR ?9.OL0 7.STA 1. CHORD ACC. FT/SEC**2

Removal and retention of phosphorus by periphyton from wastewater with high organic load.

PubMed

Cao, Jinxiang; Hong, Xiaoxing; Pei, Guofeng

2014-01-01

The total phosphorus (TP) removal efficiency from organic wastewater (pig farm and distillery wastewater) were estimated by using filamentous green algae (FGA) and benthic algal mats (BAM) treatment systems under laboratory conditions, and the contents of periphyton phosphorus fractions were determined by using a sequential extraction. The removal rates of TP reached 59-78% within the first 8 days of all treatment systems and could achieve average 80% during 30 day period, and the phosphorus removal rates by using BAM was higher than that of FGA. The ability of retention TP of periphyton enhanced gradually, the BAM TP contents were higher than that of FGA, the highest TP concentrations of BAM and FGA were 26.24 and 10.52 mg P g(-1)·dry weight. Inorganic phosphorus (IP) always exceeded 67.5% of TP, but the organic phosphorus fraction only made up less than 20% of TP. The calcium-binding phosphorus (Ca-P) was the dominant fraction and its relative contribution to TP was more than 40%. The TP was also strongly and positively correlated with the IP and Ca-P (p < 0.01) in periphyton. It showed that the periphyton had a potential ability of rapid phosphorus removing and remarkable retention from wastewater with high load phosphorus.

TP53 copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants

PubMed Central

Sulak, Michael; Fong, Lindsey; Mika, Katelyn; Chigurupati, Sravanthi; Yon, Lisa; Mongan, Nigel P; Emes, Richard D; Lynch, Vincent J

2016-01-01

A major constraint on the evolution of large body sizes in animals is an increased risk of developing cancer. There is no correlation, however, between body size and cancer risk. This lack of correlation is often referred to as 'Peto's Paradox'. Here, we show that the elephant genome encodes 20 copies of the tumor suppressor gene TP53 and that the increase in TP53 copy number occurred coincident with the evolution of large body sizes, the evolution of extreme sensitivity to genotoxic stress, and a hyperactive TP53 signaling pathway in the elephant (Proboscidean) lineage. Furthermore, we show that several of the TP53 retrogenes (TP53RTGs) are transcribed and likely translated. While TP53RTGs do not appear to directly function as transcription factors, they do contribute to the enhanced sensitivity of elephant cells to DNA damage and the induction of apoptosis by regulating activity of the TP53 signaling pathway. These results suggest that an increase in the copy number of TP53 may have played a direct role in the evolution of very large body sizes and the resolution of Peto's paradox in Proboscideans. DOI: http://dx.doi.org/10.7554/eLife.11994.001 PMID:27642012

Systemic administration of thrombin peptide TP508 enhances VEGF-stimulated angiogenesis and attenuates effects of chronic hypoxia

PubMed Central

Olszewska-Pazdrak, Barbara; Carney, Darrell H.

2015-01-01

Revascularization of chronic wounds and ischemic tissue is attenuated by endothelial dysfunction and the inability of angiogenic factors to stimulate angiogenesis. We recently showed that TP508, a nonproteolytic thrombin peptide, increases perfusion and NO-dependent vasodilation in hearts with chronic ischemia and stimulates NO production by endothelial cells. In this study, we investigated systemic in vivo effects of TP508 on VEGF-stimulated angiogenesis in vitro using aortic explants in normoxic and hypoxic conditions. Mice were injected with saline or TP508 and 24h later aortas were removed and cultured to quantify endothelial sprouting. TP508 injection increased endothelial sprouting and potentiated the in vitro response to VEGF. Exposure of control explants to hypoxia inhibited basal and VEGF-stimulated endothelial cell sprouting. This effect of hypoxia was significantly prevented by TP508 injection. Thus, TP508 systemic administration increases responsiveness of aortic endothelial cells to VEGF and diminishes the effect of chronic hypoxia on endothelial cell sprouting. Studies using human endothelial cells in culture suggest that protective effects of TP508 during hypoxia may involve stimulation of endothelial cell NO production. These data suggest potential clinical benefit of using a combination of systemic TP508 and local VEGF as a therapy for revascularization of ischemic tissue. PMID:23594718

Phosphatidylcholine transfer protein interacts with thioesterase superfamily member 2 to attenuate insulin signaling.

PubMed

Ersoy, Baran A; Tarun, Akansha; D'Aquino, Katharine; Hancer, Nancy J; Ukomadu, Chinweike; White, Morris F; Michel, Thomas; Manning, Brendan D; Cohen, David E

2013-07-30

Phosphatidylcholine transfer protein (PC-TP) is a phospholipid-binding protein that is enriched in liver and that interacts with thioesterase superfamily member 2 (THEM2). Mice lacking either protein exhibit improved hepatic glucose homeostasis and are resistant to diet-induced diabetes. Insulin receptor substrate 2 (IRS2) and mammalian target of rapamycin complex 1 (mTORC1) are key effectors of insulin signaling, which is attenuated in diabetes. We found that PC-TP inhibited IRS2, as evidenced by insulin-independent IRS2 activation after knockdown, genetic ablation, or chemical inhibition of PC-TP. In addition, IRS2 was activated after knockdown of THEM2, providing support for a role for the interaction of PC-TP with THEM2 in suppressing insulin signaling. Additionally, we showed that PC-TP bound to tuberous sclerosis complex 2 (TSC2) and stabilized the components of the TSC1-TSC2 complex, which functions to inhibit mTORC1. Preventing phosphatidylcholine from binding to PC-TP disrupted interactions of PC-TP with THEM2 and TSC2, and disruption of the PC-TP-THEM2 complex was associated with increased activation of both IRS2 and mTORC1. In livers of mice with genetic ablation of PC-TP or that had been treated with a PC-TP inhibitor, steady-state amounts of IRS2 were increased, whereas those of TSC2 were decreased. These findings reveal a phospholipid-dependent mechanism that suppresses insulin signaling downstream of its receptor.

Long noncoding RNA TP73-AS1 promotes non-small cell lung cancer progression by competitively sponging miR-449a/EZH2.

PubMed

Zhang, Lin; Fang, Fengqi; He, Xin

2018-08-01

Long noncoding RNAs (lncRNAs) are a type of noncoding RNA transcript that are characterized by lack of protein-coding capacity. The vital role of lncRNAs in non-small cell lung cancer (NSCLC) is attracting increasingly more attention. In the present study, we investigate the role of lncRNA antisense RNA of the TP73 gene (TP73-AS1) in NSCLC carcinogenesis. The results demonstrate that TP73-AS1 is markedly upregulated in NSCLC tissues, and functional experiments revealed that TP73-AS1 is significantly increased in NSCLC tissue and cell lines, indicating a possible oncogenic role. In loss-of-function assays, the knockdown of TP73-AS1 inhibited NSCLC cell proliferation, tumor growth and cycle progression in vivo and in vitro. Bioinformatic tools predicted that miR-449a both targeted the 3'-UTR of TP73-AS1 and EZH2, which was confirmed using luciferase reporter assay and AGO2-dependent RNA immunoprecipitate (RIP). TP73-AS1 and miR-449a were in the same RNA-induced silencing complex (RISC). In summary, the results indicate an explicit oncogenic role of TP73-AS1 in the NSCLC tumorigenesis, suggesting a TP73-AS1-miR-449a-EZH2 axis and providing new insight for NSCLC tumorigenesis. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Low-burden TP53 mutations in chronic phase of myeloproliferative neoplasms: association with age, hydroxyurea administration, disease type and JAK2 mutational status

PubMed Central

Kubesova, B; Pavlova, S; Malcikova, J; Kabathova, J; Radova, L; Tom, N; Tichy, B; Plevova, K; Kantorova, B; Fiedorova, K; Slavikova, M; Bystry, V; Kissova, J; Gisslinger, B; Gisslinger, H; Penka, M; Mayer, J; Kralovics, R; Pospisilova, S; Doubek, M

2018-01-01

The multistep process of TP53 mutation expansion during myeloproliferative neoplasm (MPN) transformation into acute myeloid leukemia (AML) has been documented retrospectively. It is currently unknown how common TP53 mutations with low variant allele frequency (VAF) are, whether they are linked to hydroxyurea (HU) cytoreduction, and what disease progression risk they carry. Using ultra-deep next-generation sequencing, we examined 254 MPN patients treated with HU, interferon alpha-2a or anagrelide and 85 untreated patients. We found TP53 mutations in 50 cases (0.2–16.3% VAF), regardless of disease subtype, driver gene status and cytoreduction. Both therapy and TP53 mutations were strongly associated with older age. Over-time analysis showed that the mutations may be undetectable at diagnosis and slowly increase during disease course. Although three patients with TP53 mutations progressed to TP53-mutated or TP53-wild-type AML, we did not observe a significant age-independent impact on overall survival during the follow-up. Further, we showed that complete p53 inactivation alone led to neither blast transformation nor HU resistance. Altogether, we revealed patient's age as the strongest factor affecting low-burden TP53 mutation incidence in MPN and found no significant age-independent association between TP53 mutations and hydroxyurea. Mutations may persist at low levels for years without an immediate risk of progression. PMID:28744014

Performance Evaluation of a Novel Chemiluminescence Assay Detecting Treponema Pallidum Antibody as a Syphilis Screening Method.

PubMed

Chen, Qixia; An, Jingna; Rao, Chenli; Wang, Tingting; Li, Dongdong; Feng, Shu; Tao, Chuanmin

2016-01-01

Syphilis is a major concern to global public health with increasing incidence. So its screening test should have sufficient sensitivity and specificity. We evaluated the performance of the Lumipulse G TP-N assay detection for syphilis screening and compared it with the InTec ELISA test kit for TP, which is widely used. Samples of several patient groups including 133 clinical and serologically characterized syphilitic sera, 175 samples containing potentially interfering agents, and 2290 unselected samples submitted for routine screening were detected by both the Lumipulse G TP-N assay and the InTec ELISA test kit for TP. Inconsistent samples were confirmed by RecomLine Treponema IgG, IgM immunoblot. Coefficient of variations of the Lumipulseo G TP-N assay at both levels were below 5% and of the InTec ELISA test kit for TP both over 5%. The sensitivity of the Lumipulse G TP-N assay and the InTec ELISA test kit for TP were 100% for all stages of syphilis. The two methods had consistent analytical specificity of 100% (95% CI: 97.21 - 100.00), while the clinical specificity was 100% (95% CI: 99.79 - 100.00) and 99.82% (95% CI: 99.51 - 99.94), respectively. Between them, Spearman's correlation coefficient was 0.455 and kappa value was 0.986. The overall sensitivity and specificity of the Lumipulse G TP-N assay was higher than the InTec ELISA test kit for TP (sensitivity: 100.0 versus 99.5, specificity: 100.0 versus 99.8). The automated Lumipulse G TP-N assay demonstrated excellent diagnostic sensitivity and specificity when evaluated as a screening test for syphilis. Thus, it can be an alternative to the treponemal screening test.

Effect of Vanadium and Tea Polyphenols on Intestinal Morphology, Microflora and Short-Chain Fatty Acid Profile of Laying Hens.

PubMed

Yuan, Z H; Wang, J P; Zhang, K Y; Ding, X M; Bai, S P; Zeng, Q F; Xuan, Y; Su, Z W

2016-12-01

Vanadium (V) is a trace element which can induce dysfunction of gastro-intestine and egg quality deterioration of laying hens. This study was conducted to determine the effect of tea polyphenols (TP) on intestinal morphology, microflora, and short-chain fatty acid (SCFA) profile of laying hens fed vanadium containing diets. A total of 120 Lohman laying hens (67-week-old) were randomly divided into 4 groups with 6 replicates and 5 birds each for a 35-day feeding trial. The dietary treatments were as follows: (1) control (CON), fed a basal diet; (2) vanadium treatment (V10), CON +10 mg V/kg; (3) TP treatment 1 (TP1): V10 + 600 mg TP/kg; (4) TP treatment 2 (TP2): V10 + 1000 mg TP/kg. Fed 10 mg V/kg diets to laying hens did not affect the cecum flora diversity index (H), degree of homogeneity (EH), and richness (S), but hens fed TP2 diet decreased the H, EH, and S (P < 0.05). The cecum butyrate acid concentration was lower in V10 treatment and higher in TP2 treatment (P < 0.05). Addition of 10 mg/kg V resulted in an increased (P < 0.01) duodenal cell apoptosis rate, and 1000 mg/kg TP supplementation overcame (P < 0.01) this reduction effect induced by vanadium. The results indicated that supplementation of 10 mg/kg vanadium increased duodenal cell apoptosis and reduced cecum butyrate acid content. Addition of 1000 mg/kg TP increased the SCFA production to affect cecum flora ecology and protected the duodenal cell from excess apoptosis caused by vanadium.

Quantitative identification of moisture sources over the Tibetan Plateau and the relationship between thermal forcing and moisture transport

NASA Astrophysics Data System (ADS)

Pan, Chen; Zhu, Bin; Gao, Jinhui; Kang, Hanqing; Zhu, Tong

2018-02-01

Despite the importance of the Tibetan Plateau (TP) to the surrounding water cycle, the moisture sources of the TP remain uncertain. In this study, the moisture sources of the TP are quantitatively identified based on a 33-year simulation with a horizontal resolution of 1.9° × 2.5° using the Community Atmosphere Model version 5.1 (CAM5.1), in which atmospheric water tracer technology is incorporated. Results demonstrate that the major moisture sources differ over the southern TP (STP) and northern TP (NTP). During the winter, Africa, the TP, and India are the dominant source regions, contributing nearly half of the water vapour over the STP. During the summer, the tropical Indian Ocean (TIO) supplies 28.5 ± 3.6% of the water vapour over the STP and becomes the dominant source region. The dominant moisture source regions of the water vapour over the NTP are Africa (19.0 ± 2.8%) during the winter and the TP (25.8 ± 2.4%) during the summer. The overall relative contribution of each source region to the precipitation is similar to the contribution to the water vapour over the TP. Like most models, CAM5.1 generally overestimates the precipitation over the TP, yielding uncertainty in the absolute contributions to the precipitation. Composite analyses exhibit significant variations in the TIO-supplied moisture transport and precipitation over the STP during the summer alongside anomalous TP heating. This relationship between moisture transport from the TIO and the TP heating primarily involves the dynamic change in the TIO-supplied moisture flux, which further controls the variation in the TIO-contributed precipitation over the STP.

The Long Noncoding RNA TP73-AS1 Interacted with miR-124 to Modulate Glioma Growth by Targeting Inhibitor of Apoptosis-Stimulating Protein of p53.

PubMed

Xiao, Shuai; Wang, Rensheng; Wu, Xiangwei; Liu, Wen; Ma, Shanshan

2018-02-01

P73 antisense RNA 1T (non-protein coding), known as TP73-AS1 or PDAM, is a long noncoding RNA (lncRNA), which may regulate apoptosis by regulation of p53-dependent antiapoptotic genes. An abnormal change of TP73-AS1 expression was noticed in cancers. The effects of TP73-AS1 in brain glioma growth and the underlying mechanism remain unclear so far. In this study, the effect of TP73-AS1 in human brain glioma cell lines and clinical tumor samples was detected so as to reveal its role and function. In this study, TP73-AS1 was specifically upregulated in brain glioma cell lines and promoted glioma cell growth through targeting miR-124. TP73-AS1 knocking down suppressed human brain glioma cell proliferation, invasion, and metastasis in vitro. The inhibitory effect of TP73-AS1 knocking down on glioma cell proliferation and invasion could partly be restored by miR-124 inhibition. In addition, miR-124-dependent inhibitor of apoptosis-stimulating protein of p53 (iASPP) regulation was required in TP73-AS1-induced brain glioma cell growth. Data from this study revealed that TP73-AS1 inhibited the brain glioma growth and metastasis as a competing endogenous RNA (ceRNA) through miR-124-dependent iASPP regulation. In conclusion, we regarded TP73-AS1 as an oncogenic lncRNA promoting brain glioma proliferation and metastasis and a potential target for human brain glioma treatment.

Neural correlates of auditory recognition memory in the primate dorsal temporal pole

PubMed Central

Ng, Chi-Wing; Plakke, Bethany

2013-01-01

Temporal pole (TP) cortex is associated with higher-order sensory perception and/or recognition memory, as human patients with damage in this region show impaired performance during some tasks requiring recognition memory (Olson et al. 2007). The underlying mechanisms of TP processing are largely based on examination of the visual nervous system in humans and monkeys, while little is known about neuronal activity patterns in the auditory portion of this region, dorsal TP (dTP; Poremba et al. 2003). The present study examines single-unit activity of dTP in rhesus monkeys performing a delayed matching-to-sample task utilizing auditory stimuli, wherein two sounds are determined to be the same or different. Neurons of dTP encode several task-relevant events during the delayed matching-to-sample task, and encoding of auditory cues in this region is associated with accurate recognition performance. Population activity in dTP shows a match suppression mechanism to identical, repeated sound stimuli similar to that observed in the visual object identification pathway located ventral to dTP (Desimone 1996; Nakamura and Kubota 1996). However, in contrast to sustained visual delay-related activity in nearby analogous regions, auditory delay-related activity in dTP is transient and limited. Neurons in dTP respond selectively to different sound stimuli and often change their sound response preferences between experimental contexts. Current findings suggest a significant role for dTP in auditory recognition memory similar in many respects to the visual nervous system, while delay memory firing patterns are not prominent, which may relate to monkeys' shorter forgetting thresholds for auditory vs. visual objects. PMID:24198324

TLR4 has a TP53-dependent dual role in regulating breast cancer cell growth

PubMed Central

Haricharan, Svasti; Brown, Powel

2015-01-01

Breast cancer is a leading cause of cancer-related death, and it is important to understand pathways that drive the disease to devise effective therapeutic strategies. Our results show that Toll-like receptor 4 (TLR4) drives breast cancer cell growth differentially based on the presence of TP53, a tumor suppressor. TP53 is mutationally inactivated in most types of cancer and is mutated in 30–50% of diagnosed breast tumors. We demonstrate that TLR4 activation inhibits growth of TP53 wild-type cells, but promotes growth of TP53 mutant breast cancer cells by regulating proliferation. This differential effect is mediated by changes in tumor cell cytokine secretion. Whereas TLR4 activation in TP53 mutant breast cancer cells increases secretion of progrowth cytokines, TLR4 activation in TP53 wild-type breast cancer cells increases type I IFN (IFN-γ) secretion, which is both necessary and sufficient for mediating TLR4-induced growth inhibition. This study identifies a novel dichotomous role for TLR4 as a growth regulator and a modulator of tumor microenvironment in breast tumors. These results have translational relevance, demonstrating that TP53 mutant breast tumor growth can be suppressed by pharmacologic TLR4 inhibition, whereas TLR4 inhibitors may in fact promote growth of TP53 wild-type tumors. Furthermore, using data generated by The Cancer Genome Atlas consortium, we demonstrate that the effect of TP53 mutational status on TLR4 activity may extend to ovarian, colon, and lung cancers, among others, suggesting that the viability of TLR4 as a therapeutic target depends on TP53 status in many different tumor types. PMID:26063617

TLR4 has a TP53-dependent dual role in regulating breast cancer cell growth.

PubMed

Haricharan, Svasti; Brown, Powel

2015-06-23

Breast cancer is a leading cause of cancer-related death, and it is important to understand pathways that drive the disease to devise effective therapeutic strategies. Our results show that Toll-like receptor 4 (TLR4) drives breast cancer cell growth differentially based on the presence of TP53, a tumor suppressor. TP53 is mutationally inactivated in most types of cancer and is mutated in 30-50% of diagnosed breast tumors. We demonstrate that TLR4 activation inhibits growth of TP53 wild-type cells, but promotes growth of TP53 mutant breast cancer cells by regulating proliferation. This differential effect is mediated by changes in tumor cell cytokine secretion. Whereas TLR4 activation in TP53 mutant breast cancer cells increases secretion of progrowth cytokines, TLR4 activation in TP53 wild-type breast cancer cells increases type I IFN (IFN-γ) secretion, which is both necessary and sufficient for mediating TLR4-induced growth inhibition. This study identifies a novel dichotomous role for TLR4 as a growth regulator and a modulator of tumor microenvironment in breast tumors. These results have translational relevance, demonstrating that TP53 mutant breast tumor growth can be suppressed by pharmacologic TLR4 inhibition, whereas TLR4 inhibitors may in fact promote growth of TP53 wild-type tumors. Furthermore, using data generated by The Cancer Genome Atlas consortium, we demonstrate that the effect of TP53 mutational status on TLR4 activity may extend to ovarian, colon, and lung cancers, among others, suggesting that the viability of TLR4 as a therapeutic target depends on TP53 status in many different tumor types.

DOR/Tp53inp2 and Tp53inp1 constitute a metazoan gene family encoding dual regulators of autophagy and transcription.

PubMed

Sancho, Ana; Duran, Jordi; García-España, Antonio; Mauvezin, Caroline; Alemu, Endalkachew A; Lamark, Trond; Macias, Maria J; DeSalle, Rob; Royo, Miriam; Sala, David; Chicote, Javier U; Palacín, Manuel; Johansen, Terje; Zorzano, Antonio

2012-01-01

Human DOR/TP53INP2 displays a unique bifunctional role as a modulator of autophagy and gene transcription. However, the domains or regions of DOR that participate in those functions have not been identified. Here we have performed structure/function analyses of DOR guided by identification of conserved regions in the DOR gene family by phylogenetic reconstructions. We show that DOR is present in metazoan species. Invertebrates harbor only one gene, DOR/Tp53inp2, and in the common ancestor of vertebrates Tp53inp1 may have arisen by gene duplication. In keeping with these data, we show that human TP53INP1 regulates autophagy and that different DOR/TP53INP2 and TP53INP1 proteins display transcriptional activity. The use of molecular evolutionary information has been instrumental to determine the regions that participate in DOR functions. DOR and TP53INP1 proteins share two highly conserved regions (region 1, aa residues 28-42; region 2, 66-112 in human DOR). Mutation of conserved hydrophobic residues in region 1 of DOR (that are part of a nuclear export signal, NES) reduces transcriptional activity, and blocks nuclear exit and autophagic activity under autophagy-activated conditions. We also identify a functional and conserved LC3-interacting motif (LIR) in region 1 of DOR and TP53INP1 proteins. Mutation of conserved acidic residues in region 2 of DOR reduces transcriptional activity, impairs nuclear exit in response to autophagy activation, and disrupts autophagy. Taken together, our data reveal DOR and TP53INP1 as dual regulators of transcription and autophagy, and identify two conserved regions in the DOR family that concentrate multiple functions crucial for autophagy and transcription.

DOR/Tp53inp2 and Tp53inp1 Constitute a Metazoan Gene Family Encoding Dual Regulators of Autophagy and Transcription

PubMed Central

Sancho, Ana; Duran, Jordi; García-España, Antonio; Mauvezin, Caroline; Alemu, Endalkachew A.; Lamark, Trond; Macias, Maria J.; DeSalle, Rob; Royo, Miriam; Sala, David; Chicote, Javier U.; Palacín, Manuel; Johansen, Terje; Zorzano, Antonio

2012-01-01

Human DOR/TP53INP2 displays a unique bifunctional role as a modulator of autophagy and gene transcription. However, the domains or regions of DOR that participate in those functions have not been identified. Here we have performed structure/function analyses of DOR guided by identification of conserved regions in the DOR gene family by phylogenetic reconstructions. We show that DOR is present in metazoan species. Invertebrates harbor only one gene, DOR/Tp53inp2, and in the common ancestor of vertebrates Tp53inp1 may have arisen by gene duplication. In keeping with these data, we show that human TP53INP1 regulates autophagy and that different DOR/TP53INP2 and TP53INP1 proteins display transcriptional activity. The use of molecular evolutionary information has been instrumental to determine the regions that participate in DOR functions. DOR and TP53INP1 proteins share two highly conserved regions (region 1, aa residues 28–42; region 2, 66–112 in human DOR). Mutation of conserved hydrophobic residues in region 1 of DOR (that are part of a nuclear export signal, NES) reduces transcriptional activity, and blocks nuclear exit and autophagic activity under autophagy-activated conditions. We also identify a functional and conserved LC3-interacting motif (LIR) in region 1 of DOR and TP53INP1 proteins. Mutation of conserved acidic residues in region 2 of DOR reduces transcriptional activity, impairs nuclear exit in response to autophagy activation, and disrupts autophagy. Taken together, our data reveal DOR and TP53INP1 as dual regulators of transcription and autophagy, and identify two conserved regions in the DOR family that concentrate multiple functions crucial for autophagy and transcription. PMID:22470510

Autophagy is induced through the ROS-TP53-DRAM1 pathway in response to mitochondrial protein synthesis inhibition.

PubMed

Xie, Xiaolei; Le, Li; Fan, Yanxin; Lv, Lin; Zhang, Junjie

2012-07-01

Mitoribosome in mammalian cells is responsible for synthesis of 13 mtDNA-encoded proteins, which are integral parts of four mitochondrial respiratory chain complexes (I, III, IV and V). ERAL1 is a nuclear-encoded GTPase important for the formation of the 28S small mitoribosomal subunit. Here, we demonstrate that knockdown of ERAL1 by RNA interference inhibits mitochondrial protein synthesis and promotes reactive oxygen species (ROS) generation, leading to autophagic vacuolization in HeLa cells. Cells that lack ERAL1 expression showed a significant conversion of LC3-I to LC3-II and an enhanced accumulation of autophagic vacuoles carrying the LC3 marker, all of which were blocked by the autophagy inhibitor 3-MA as well as by the ROS scavenger NAC. Inhibition of mitochondrial protein synthesis either by ERAL1 siRNA or chloramphenicol (CAP), a specific inhibitor of mitoribosomes, induced autophagy in HTC-116 TP53 (+/+) cells, but not in HTC-116 TP53 (-/-) cells, indicating that tumor protein 53 (TP53) is essential for the autophagy induction. The ROS elevation resulting from mitochondrial protein synthesis inhibition induced TP53 expression at transcriptional levels by enhancing TP53 promoter activity, and increased TP53 protein stability by suppressing TP53 ubiquitination through MAPK14/p38 MAPK-mediated TP53 phosphorylation. Upregulation of TP53 and its downstream target gene DRAM1, but not CDKN1A/p21, was required for the autophagy induction in ERAL1 siRNA or CAP-treated cells. Altogether, these data indicate that autophagy is induced through the ROS-TP53-DRAM1 pathway in response to mitochondrial protein synthesis inhibition.

Lab-on-a-chip based total-phosphorus analysis device utilizing a photocatalytic reaction

NASA Astrophysics Data System (ADS)

Jung, Dong Geon; Jung, Daewoong; Kong, Seong Ho

2018-02-01

A lab-on-a-chip (LOC) device for total phosphorus (TP) analysis was fabricated for water quality monitoring. Many commercially available TP analysis systems used to estimate water quality have good sensitivity and accuracy. However, these systems also have many disadvantages such as bulky size, complex pretreatment processes, and high cost, which limit their application. In particular, conventional TP analysis systems require an indispensable pretreatment step, in which the fluidic analyte is heated to 120 °C for 30 min to release the dissolved phosphate, because many phosphates are soluble in water at a standard temperature and pressure. In addition, this pretreatment process requires elevated pressures of up to 1.1 kg cm-2 in order to prevent the evaporation of the heated analyte. Because of these limiting conditions required by the pretreatment processes used in conventional systems, it is difficult to miniaturize TP analysis systems. In this study, we employed a photocatalytic reaction in the pretreatment process. The reaction was carried out by illuminating a photocatalytic titanium dioxide (TiO2) surface formed in a microfluidic channel with ultraviolet (UV) light. This pretreatment process does not require elevated temperatures and pressures. By applying this simplified, photocatalytic-reaction-based pretreatment process to a TP analysis system, greater degrees of freedom are conferred to the design and fabrication of LOC devices for TP monitoring. The fabricated LOC device presented in this paper was characterized by measuring the TP concentration of an unknown sample, and comparing the results with those measured by a conventional TP analysis system. The TP concentrations of the unknown sample measured by the proposed LOC device and the conventional TP analysis system were 0.018 mgP/25 mL and 0.019 mgP/25 mL, respectively. The experimental results revealed that the proposed LOC device had a performance comparable to the conventional bulky TP analysis system. Therefore, our device could be directly employed in water quality monitoring as an alternative to conventional TP analysis systems.

Synthesis, structure and reactivity of a terminal magnesium fluoride compound, [TpBut,Me]MgF: hydrogen bonding, halogen bonding and C-F bond formation.

PubMed

Rauch, Michael; Ruccolo, Serge; Mester, John Paul; Rong, Yi; Parkin, Gerard

2016-01-01

The bulky tris(3- tert -butyl-5-pyrazolyl)hydroborato ligand, [Tp Bu t ,Me ], has been employed to obtain the first structurally characterized example of a molecular magnesium compound that features a terminal fluoride ligand, namely [Tp Bu t ,Me ]MgF, via the reaction of [Tp Bu t ,Me ]MgMe with Me 3 SnF. The chloride, bromide and iodide complexes, [Tp Bu t ,Me ]MgX (X = Cl, Br, I), can also be obtained by an analogous method using Me 3 SnX. The molecular structures of the complete series of halide derivatives, [Tp Bu t ,Me ]MgX (X = F, Cl, Br, I) have been determined by X-ray diffraction. In each case, the Mg-X bond lengths are shorter than the sum of the covalent radii, thereby indicating that there is a significant ionic component to the bonding, in agreement with density functional theory calculations. The fluoride ligand of [Tp Bu t ,Me ]MgF undergoes halide exchange with Me 3 SiX (X = Cl, Br, I) to afford [Tp Bu t ,Me ]MgX and Me 3 SiF. The other halide derivatives [Tp Bu t ,Me ]MgX undergo similar exchange reactions, but the thermodynamic driving forces are much smaller than those involving fluoride transfer, a manifestation of the often discussed silaphilicity of fluorine. In accord with the highly polarized Mg-F bond, the fluoride ligand of [Tp Bu t ,Me ]MgF is capable of serving as a hydrogen bond and halogen bond acceptor, such that it forms adducts with indole and C 6 F 5 I. [Tp Bu t ,Me ]MgF also reacts with Ph 3 CCl to afford Ph 3 CF, thereby demonstrating that [Tp Bu t ,Me ]MgF may be used to form C-F bonds.

Terpinen-4-ol inhibits colorectal cancer growth via reactive oxygen species

PubMed Central

Nakayama, Ken; Murata, Soichiro; Ito, Hiromu; Iwasaki, Kenichi; Villareal, Myra Orlina; Zheng, Yun-Wen; Matsui, Hirofumi; Isoda, Hiroko; Ohkohchi, Nobuhiro

2017-01-01

Terpinen-4-ol (TP4O) is the main component of the essential oil extracted from Melaleuca alternifolia, known as the tea tree, of the botanical family Myrtaceae. The anticancer effects of TP4O have been reported in several cancer cell lines. Previous reports have demonstrated that TP4O exerts anticancer effects by inducing apoptotic cell death in several cell lines; however, the underlying molecular mechanisms of these effects remain unclear. In the present study, the anticancer effects of TP4O against the colorectal cancer (CRC) cell lines HCT116 and RKO were evaluated using WST-8 and bromodeoxyuridine assays. The mechanism of cell death was investigated by the measurement of caspase-3/7, Annexin V and lactate dehydrogenase release. Reactive oxygen species (ROS) levels induced by TP4O were evaluated by electron spin resonance and quantitative measurement of dihydroethidium. Localization of the ROS derived from mitochondria was observed by confocal inverted microscopy. Protein levels of ROS scavengers were assessed by western blotting analysis. To confirm the role of ROS, cell viability was measured in the presence of antioxidant reagents. In an in vivo xenograft model of ICR-SCID mice implanted with HCT116 cells, 200 mg/kg TP4O was injected locally, and tumor growth was compared with that of the control. TP4O induced apoptotic cell death in HCT116 and RKO cells in a dose-dependent manner, and TP4O also increased the levels of ROS generated by mitochondria. TP4O-induced cell death was rescued by administration of antioxidant regents. In vivo, TP4O inhibited the proliferation of HCT116 xenografts compared with that of the control group. The results of the present study suggest that TP4O induces apoptosis in CRC cells through ROS generation. Furthermore, TP4O is potentially useful for the development of novel therapies against CRC. PMID:28781645

Erosion-protecting effect of oral-care products available on the Swiss market. A pilot study

PubMed

Wasser, Gregor; João-Souza, Samira H; Lussi, Adrian; Carvalho, Thiago S

2018-03-28

The present study sought to test oral-care products available on the Swiss market, such as toothpastes and gels, with respect to the protection of enamel against erosive tooth wear. A total of 56 enamel specimens were divided into 7 groups (n = 8): F-TP = Migros Budget Anti-Caries Toothpaste (Negative Control); F+Sn3500-TP = Elmex Erosion Protection Toothpaste (Positive Control); F-TP + F+Oligopep-Gel = Migros Budget Anti-Caries Toothpaste + Emofluor Protect Gel Professional; F+Sn3120-Gel = Emofluor Gel Intensive Care; F+Oligopep-TP = Candida Protect Professional Toothpaste; F+Sn1260-TP = Emoform-F Protect Toothpaste; and F+Sn3440-TP = Sensodyne Repair & Protect Toothpaste. The specimens were incubated in artificial saliva for 30 min and then brushed in a toothbrushing machine (10 s brushing; total 2 min exposure to the product). After the toothbrush abrasion, the specimens were rinsed, dried and submitted to an erosive challenge (2 min; 1% citric acid; pH 3.6). This sequence was repeated 4 times, and the total enamel surface loss was calculated using indentation measurements before and after the brushing period. All groups presented progressive surface loss throughout the experiment; after 4 cycles, total surface loss values ranged from 0.11 µm (F+Sn3120-Gel) to 0.89 µm (F+Sn1260-TP). Regarding the total surface loss values (median; interquartile range), F-TP (0.54; 0.42–0.59) presented no significant differences compared to any of the other groups. F+Sn3500-TP (0.33; 0.30–0.40), F-TP + F+Oligopep-Gel (0.34; 0.29–0.42) and F+Sn3120-Gel (0.11; 0.09–0.15) presented lower surface loss than F+Oligopep-TP (0.75; 0.59–0.98), F+Sn1260-TP (0.89; 0.68–1.13) and F+Sn3440-TP (0.69; 0.66–0.78). Conclusion: Although some of the oral-care products containing stannous ions or oligopeptide-104 presented numerically lower SL values, they did not present significantly better protection than a regular fluoride toothpaste. The gels showed a general trend of better enamel protection against ETW.

Tpeak - Tend and Tpeak - Tend /QT ratio as markers of ventricular arrhythmia risk in cardiac resynchronization therapy patients.

PubMed

Barbhaiya, Chirag; Po, Jose Ricardo F; Hanon, Sam; Schweitzer, Paul

2013-01-01

Cardiac resynchronization therapy (CRT) increases transmural dispersion of repolarization (TDR) and can be pro-arrhythmic. However, overall arrhythmia risk was not increased in large-scale CRT clinical trials. Increased TDR as measured by T(peak ) -T(end) (TpTe) was associated with arrhythmia risk in CRT in a single-center study. This study investigates whether QT interval, TpTe, and TpTe/QT ratio are associated with ventricular arrhythmias in patients with CRT-defibrillator (CRT-D). Post-CRT-D implant electrocardiograms of 128 patients (age 71.3 years ± 10.3) with at least 2 months of follow-up at our institution's device clinic (mean follow-up of 28.5 months ± 17) were analyzed for QT interval, TpTe, and TpTe/QT ratio. Incidence of ventricular arrhythmias was determined based on routine and directed device interrogations. Appropriate implantable cardioverter-defibrillator therapy for sustained ventricular tachycardia or ventricular fibrillation was delivered in 18 patients (14%), and nonsustained ventricular tachycardia (NSVT) was detected but did not require therapy in 58 patients (45%). Patients who received appropriate defibrillator therapy had increased TpTe/QT ratio (0.24 ± 0.03 ms vs 0.20 ± 0.04, P = 0.0002) and increased TpTe (105.56 ± 20.36 vs 87.82 ± 22.32 ms, P = 0.002), and patients with NSVT had increased TpTe/QT ratio (0.22 ± 0.04 vs 0.20 ± 0.04, P = 0.016). Increased QT interval was not associated with risk of ventricular arrhythmia. The relative risk for appropriate defibrillator therapy of T(p) T(e) /QT ratio ≥ 0.25 was 3.24 (P = 0.016). Increased TpTe and increased TpTe/QT ratio are associated with increased incidence of ventricular arrhythmias in CRT-D. The utility of TpTe interval and TpTe/QT ratio as potentially modifiable risk factors for ventricular arrhythmias in CRT requires further study. ©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.

Exquisite Sensitivity of TP53 Mutant and Basal Breast Cancers to a Dose-Dense Epirubicin−Cyclophosphamide Regimen

PubMed Central

Espié, Marc; de Reyniès, Aurélien; Feugeas, Jean-Paul; Plassa, Louis-François; Soliman, Hany; Varna, Mariana; de Roquancourt, Anne; Lehmann-Che, Jacqueline; Beuzard, Yves; Marty, Michel; Misset, Jean-Louis; Janin, Anne; de Thé, Hugues

2007-01-01

Background In breast cancers, only a minority of patients fully benefit from the different chemotherapy regimens currently in use. Identification of markers that could predict the response to a particular regimen would thus be critically important for patient care. In cell lines or animal models, tumor protein p53 (TP53) plays a critical role in modulating the response to genotoxic drugs. TP53 is activated in response to DNA damage and triggers either apoptosis or cell-cycle arrest, which have opposite effects on cell fate. Yet, studies linking TP53 status and chemotherapy response have so far failed to unambiguously establish this paradigm in patients. Breast cancers with a TP53 mutation were repeatedly shown to have a poor outcome, but whether this reflects poor response to treatment or greater intrinsic aggressiveness of the tumor is unknown. Methods and Findings In this study we analyzed 80 noninflammatory breast cancers treated by frontline (neoadjuvant) chemotherapy. Tumor diagnoses were performed on pretreatment biopsies, and the patients then received six cycles of a dose-dense regimen of 75 mg/m2 epirubicin and 1,200 mg/m2 cyclophosphamide, given every 14 days. After completion of chemotherapy, all patients underwent mastectomies, thus allowing for a reliable assessment of chemotherapy response. The pretreatment biopsy samples were used to determine the TP53 status through a highly efficient yeast functional assay and to perform RNA profiling. All 15 complete responses occurred among the 28 TP53-mutant tumors. Furthermore, among the TP53-mutant tumors, nine out of ten of the highly aggressive basal subtypes (defined by basal cytokeratin [KRT] immunohistochemical staining) experienced complete pathological responses, and only TP53 status and basal subtype were independent predictors of a complete response. Expression analysis identified many mutant TP53-associated genes, including CDC20, TTK, CDKN2A, and the stem cell gene PROM1, but failed to identify a transcriptional profile associated with complete responses among TP53 mutant tumors. In patients with unresponsive tumors, mutant TP53 status predicted significantly shorter overall survival. The 15 patients with responsive TP53-mutant tumors, however, had a favorable outcome, suggesting that this chemotherapy regimen can overcome the poor prognosis generally associated with mutant TP53 status. Conclusions This study demonstrates that, in noninflammatory breast cancers, TP53 status is a key predictive factor for response to this dose-dense epirubicin–cyclophosphamide regimen and further suggests that the basal subtype is exquisitely sensitive to this association. Given the well-established predictive value of complete responses for long-term survival and the poor prognosis of basal and TP53-mutant tumors treated with other regimens, this chemotherapy could be particularly suited for breast cancer patients with a mutant TP53, particularly those with basal features. PMID:17388661

Copper-induced ammonia N-H functionalization.

PubMed

Álvarez, María; Álvarez, Eleuterio; Fructos, Manuel R; Urbano, Juan; Pérez, Pedro J

2016-10-07

The activation of ammonia has been achieved with the aid of the Tp(Ms)Cu core (Tp(Ms) = hydrotris(3-mesityl-pyrazolyl)borate). Complexes of the general composition Tp(Ms)Cu(amine) (1-4) including the ammonia adduct Tp(Ms)Cu(NH3) (1) have been synthesized and fully spectroscopical- and structurally characterized. Coordinated ammonia in 1 has been reacted with Ph3CPF6 yielding Tp(Ms)Cu(NH2CPh3) (5) as a result of N-H cleavage and N-C bond formation. In a parallel manner the catalytic functionalization of ammonia with ethyl diazoacetate leading to glycinate derivatives has been developed with Tp(Ms)Cu(THF) as the catalyst, in the first example of this transformation with ammonia and a copper-based system.

Antioxidant capacity and vasodilatory properties of Mediterranean food: the case of Cannonau wine, myrtle berries liqueur and strawberry-tree honey.

PubMed

Tuberoso, Carlo Ignazio Giovanni; Boban, Mladen; Bifulco, Ersilia; Budimir, Danijela; Pirisi, Filippo Maria

2013-10-15

The aim of this work was to use different assays to evaluate the antioxidant and vasodilatory properties of three typical food products from the Mediterranean area and to correlate these activities with their phenolic content. For this purpose, red wines Cannonau, liqueurs obtained by cold maceration of myrtle (Myrtus communis L.) berries and bitter honeys obtained from strawberry-tree flowers (Arbutus unedo L.) were analysed. The total phenolic (TP) content was measured spectrophotometrically with a modified Folin-Ciocalteau method and phenolic compounds were identified and dosed by HPLC-DAD and LC-MS/MS. Antioxidant activities were evaluated with DPPH, FRAP and ABTS assays and the in vitro vasodilatory effects were assessed using norepinephrine precontracted rat aortic rings. Cannonau wines and myrtle liqueurs showed high levels of TP (1978±279 and 1741±150mg GAE/L, respectively), linearly correlated to the results of FRAP, ABTS, and DPPH assays. Their maximal vasodilatory activity was 61.7±4.1% and 53.0±3.0%, respectively. Although strawberry-tree honey contained relatively high levels of phenolic compounds (922±38mg GAE/kg), it did not induce vasodilation, even at the highest dose tested (0.206g/L). These results indicate that foods with high levels of phenolic compounds should be studied using several different biological assays before being recommended to the general public as functional foods. Copyright © 2012 Elsevier Ltd. All rights reserved.

Origin of low proton-to-electron temperature ratio in the Earth's plasma sheet

NASA Astrophysics Data System (ADS)

Grigorenko, E. E.; Kronberg, E. A.; Daly, P. W.; Ganushkina, N. Yu.; Lavraud, B.; Sauvaud, J.-A.; Zelenyi, L. M.

2016-10-01

We study the proton-to-electron temperature ratio (Tp/Te) in the plasma sheet (PS) of the Earth's magnetotail using 5 years of Cluster observations (2001-2005). The PS intervals are searched within a region defined with -19 < X ≤ -7 RE and |Y| < 15 RE (GSM) under the condition |BX| ≤ 10 nT. One hundred sixty PS crossings are identified. We find an average value of 6.0. However, in many PS intervals Tp/Te varies over a wide range from a few units to several tens of units. In 86 PS intervals the Tp/Te decreases below 3.5. Generally, the decreases of Tp/Te are due to some increase of Te while Tp either decreases or remains unchanged. In the majority of these intervals the Tp/Te drops are observed during magnetotail dipolarizations. A superposed epoch analysis applied to these events shows that the minimum value of Tp/Te is observed after the dipolarization onset during the "turbulent phase" of dipolarization, when a number of transient BZ pulses are reduced, but the value of BZ is still large and an intensification of wave activity is observed. The Tp/Te drops, and associated increases of Te often coincide either with bursts of broadband electrostatic emissions, which may include electron cyclotron harmonics, or with broadband electromagnetic emission in a frequency range from proton plasma frequency (fpp) up to the electron gyrofrequency (fce). These findings show that the wave activity developing in the current sheet after dipolarization onset may play a role in the additional electron heating and the associated Tp/Te decrease.

Spontaneous and radiation-induced genomic instability in human cell lines differing in cellular TP53 status.

PubMed

Moore, Stephen R; Ritter, Linda E; Gibbons, Catherine F; Grosovsky, Andrew J

2005-10-01

Structural chromosomal rearrangements are commonly observed in tumor karyotypes and in radiation-induced genomic instability. Here we report the effects of TP53 deficiency on karyotypic stability before and after irradiation using related cells and clones differing in cellular TP53 status. The parental cell line, TK6, is a TP53 wild-type human B-lymphoblastoid line with a highly stable karyotype. In the two TK6 derivatives used here, TP53 has been inactivated by biochemical means (expression of HPV16 E6; TK6-5E) or genetic means (allelic inactivation; NH32). Biochemical inactivation of TP53 (TK6-5E) had little effect on the spontaneous karyotype, whereas allelic inactivation of TP53 (NH32) resulted in a modest increase in spontaneous karyotypic instability. After 2 Gy gamma irradiation, the number of unstable clones derived from TP53-deficient cells was significantly elevated compared to the TP53 wild-type counterpart. Extensively destabilized clones were common after irradiation in the set of clones derived from NH32 cells, and one was observed in the set of TK6-5E clones; however, they were never observed in TK6-derived clones. In two of the irradiated NH32 clones, whole chromosomes or chromosome bands were preferentially involved in alterations. These results suggest that genomic instability may differ both quantitatively and qualitatively as a consequence of altered TP53 expression. Some of the results showing repeated and preferential chromosome involvement in aberrations support a model in which instability may be driven by cis mechanisms.

Glycyrrhetinic Acid Accelerates the Clearance of Triptolide through P-gp In Vitro.

PubMed

Li, Zhihua; Yan, Miao; Cao, Lingjuan; Fang, Pingfei; Guo, Zhaohui; Hou, Zhenyan; Zhang, Bikui

2017-07-01

Triptolide (TP) is an active ingredient isolated from Tripterygium wilfordii Hook. f. (TWHF), which is a traditional herbal medicine widely used for the treatment of rheumatoid arthritis and autoimmune disease in the clinic. However, its adverse reactions of hepatotoxicity and nephrotoxicity have been frequently reported which limited its clinical application. The aim of this study was to investigate the mechanism of glycyrrhetinic acid (GA) effecting on the elimination of TP in HK-2 cells and the role of the efflux transporters of P-gp and multidrug resistance-associated proteins (MRPs) in this process. An ultra performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS) analytical method was established to determine the intracellular concentration of TP. In order to study the role of efflux transporters of P-gp and MRPs in GA impacting on the accumulation of TP, the inhibitors of efflux transporters (P-gp: verapamil; MRPs: MK571) were used in this study. The results showed that GA could enhance the elimination of TP and reduce the TP accumulation in HK-2 cells. Verapamil and MK571 could increase the intracellular concentration of TP; in addition, GA co-incubation with verapamil significantly increased the TP cellular concentration compared with the control group. In conclusion, GA could reduce the accumulation of TP in HK-2 cells, which was related to P-gp. This is probably one of the mechanisms that TP combined with GA to detoxify its toxicity. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

TP53 Mutation Status of Tubo-ovarian and Peritoneal High-grade Serous Carcinoma with a Wild-type p53 Immunostaining Pattern.

PubMed

Na, Kiyong; Sung, Ji-Youn; Kim, Hyun-Soo

2017-12-01

Diffuse and strong nuclear p53 immunoreactivity and a complete lack of p53 expression are regarded as indicative of missense and nonsense mutations, respectively, of the TP53 gene. Tubo-ovarian and peritoneal high-grade serous carcinoma (HGSC) is characterized by aberrant p53 expression induced by a TP53 mutation. However, our experience with some HGSC cases with a wild-type p53 immunostaining pattern led us to comprehensively review previous cases and investigate the TP53 mutational status of the exceptional cases. We analyzed the immunophenotype of 153 cases of HGSC and performed TP53 gene sequencing analysis in those with a wild-type p53 immunostaining pattern. Immunostaining revealed that 109 (71.3%) cases displayed diffuse and strong p53 expression (missense mutation pattern), while 39 (25.5%) had no p53 expression (nonsense mutation pattern). The remaining five cases of HGSC showed a wild-type p53 immunostaining pattern. Direct sequencing analysis revealed that three of these cases harbored nonsense TP53 mutations and two had novel splice site deletions. TP53 mutation is almost invariably present in HGSC, and p53 immunostaining can be used as a surrogate marker of TP53 mutation. In cases with a wild-type p53 immunostaining pattern, direct sequencing for TP53 mutational status can be helpful to confirm the presence of a TP53 mutation. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Extending water vapor trend observations over Boulder into the tropopause region: Trend uncertainties and resulting radiative forcing.

PubMed

Kunz, A; Müller, R; Homonnai, V; Jánosi, I M; Hurst, D; Rap, A; Forster, P M; Rohrer, F; Spelten, N; Riese, M

2013-10-16

Thirty years of balloon-borne measurements over Boulder (40°N, 105°W) are used to investigate the water vapor trend in the tropopause region. This analysis extends previously published trends, usually focusing on altitudes greater than 16 km, to lower altitudes. Two new concepts are applied: (1) Trends are presented in a thermal tropopause (TP) relative coordinate system from -2 km below to 10 km above the TP, and (2) sonde profiles are selected according to TP height. Tropical (TP z > 14 km), extratropical (TP z < 12 km), and transitional air mass types (12 km < TP z < 14 km) reveal three different water vapor reservoirs. The analysis based on these concepts reduces the dynamically induced water vapor variability at the TP and principally favors refined water vapor trend studies in the upper troposphere and lower stratosphere. Nonetheless, this study shows how uncertain trends are at altitudes -2 to +4 km around the TP. This uncertainty in turn has an influence on the uncertainty and interpretation of water vapor radiative effects at the TP, which are locally estimated for the 30 year period to be of uncertain sign. The much discussed decrease in water vapor at the beginning of 2001 is not detectable between -2 and 2 km around the TP. On lower stratospheric isentropes, the water vapor change at the beginning of 2001 is more intense for extratropical than for tropical air mass types. This suggests a possible link with changing dynamics above the jet stream such as changes in the shallow branch of the Brewer-Dobson circulation.

Crystal structure of thermostable p-nitrophenylphosphatase from Bacillus Stearothermophilus (Bs-TpNPPase).

PubMed

Guo, Zheng; Wang, Fengbin; Shen, Tiantian; Huang, Jing; Wang, Yuandong; Ji, Chaoneng

2014-05-01

Thermostable p-nitrophenylphosphatase from Bacillus Stearothermophilus (Bs-TpNPPase) is involved in the Mg(2+)-dependent hydrolysis of the phosphoenzyme at an optimum reaction temperature of 55°C. Bs-TpNPPase has been cloned and overexpressed in the E.coli M15 strain. Based on the conserved active sites, the protein was suggested to be a member of the haloalkanoate dehalogenase (HAD) superfamily. Two site-specific point mutants of Bs-TpNPPase were prepared by changing the catalytic Asp10 and Thr43 to Ala10 and Ala43, respectively. The activity of the two mutants further confirms Bs-TpNPPase as a member of the HAD superfamily. HAD superfamily can be divided into the four subfamilies and play several biochemical roles such as DNA repair, signal transduction and secondary metabolism. To understand the relationship between structure and thermostability in HAD superfamily, Bs-TpNPPase from Bacillus Stearothermophilus was selected. The X-ray crystal structure of Bs-TpNPPase was determined at 1.5A resolution using the molecular replacement phasing method. The structure of Bs-TpNPPase has been deposited and the PDB code is 4KN8. Compared with Bsp, a mesophilic prokaryotic putative p-nitrophenyl phosphatase from Bacillus Subtilis, Bs- TpNPPase showed highly homology but variations in the level of leucine content, aromatic clusters, cation-Pi and hydrophobic interaction. These differences may affect the thermal stability of the protein. The crystal structure of Bs-TpNPPase described herein may serve as a guide to better understand the mechanism of thermostability and provide insights for further mutation work.

Effect of rye bread enriched with tomato pomace on fat absorption and lipid metabolism in rats fed a high-fat diet.

PubMed

Bajerska, Joanna; Chmurzynska, Agata; Mildner-Szkudlarz, Sylwia; Drzymała-Czyż, Sławomira

2015-07-01

Tomato pomace (TP), obtained as a residue of tomato processing, was used to enrich rye bread (RB). The sensory profile of this functional bread (RB+TP) was characterised, and its fat absorption and lipid metabolism properties in high-fat-fed rats were studied. Intake of the HF diet containing RB, RB+TP, or TP alone increased faecal energy and fat excretion, but did not affect animal growth or visceral fat weight. Both RB and RB+TP diminished the negative impact of the HF diet, lowering the atherogenic index of plasma (AIP) and the total liver lipid contents by 31.6% and 24%, respectively. The experimental diets had no effect on liver S-adenosylhomocysteine (SAH) concentrations or on the S-adenosylmethionine (SAM) to SAH ratio, though the lowest SAM levels were observed in the HF+TP group. No significant differences were detected in blood homocysteine, triglycerides, glucose or insulin levels. Although RB+TP incorporated into a HF diet may lead to a decrease in AIP and total liver lipid content, this effect does not depend on the components of TP, but rather on the RB ingredients. However, pure TP, in the doses used in this study, may potentially play a role in the energy balance via faecal loss of lipids. © 2014 Society of Chemical Industry.

Expression of TpNRAMP5, a metal transporter from Polish wheat (Triticum polonicum L.), enhances the accumulation of Cd, Co and Mn in transgenic Arabidopsis plants.

PubMed

Peng, Fan; Wang, Chao; Zhu, Jianshu; Zeng, Jian; Kang, Houyang; Fan, Xing; Sha, Lina; Zhang, Haiqin; Zhou, Yonghong; Wang, Yi

2018-06-01

TpRNAMP5 is mainly expressed in the plasma membrane of roots and basal stems. It functions as a metal transporter for Cd, Mn and Co accumulation. Numerous natural resistance-associated macrophage proteins (NRAMPs) have been functionally identified in various plant species, including Arabidopsis, rice, soybean and tobacco, but no information is available on NRAMP genes in wheat. In this study, we isolated a TpNRAMP5 from dwarf Polish wheat (DPW, Triticum polonicum L.), a species with high tolerance to Cd and Zn. Expression pattern analysis revealed that TpNRAMP5 is mainly expressed in roots and basal stems of DPW. TpNRAMP5 was localized at the plasma membrane of Arabidopsis leaf protoplast. Expression of TpNRAMP5 in yeast significantly increased yeast sensitivity to Cd and Co, but not Zn, and enhanced Cd and Co concentrations. Expression of TpNRAMP5 in Arabidopsis significantly increased Cd, Co and Mn concentrations in roots, shoots and whole plants, but had no effect on Fe and Zn concentrations. These results indicate that TpNRAMP5 is a metal transporter enhancing the accumulation of Cd, Co and Mn, but not Zn and Fe. Genetic manipulation of TpNRAMP5 can be applied in the future to limit the transfer of Cd from soil to wheat grains, thereby protecting human health.

Time perspective as a predictor of massive multiplayer online role-playing game playing.

PubMed

Lukavska, Katerina

2012-01-01

This article focuses on the relationship between the time perspective (TP) personality trait and massive multiplayer online role-playing game (MMORPG) playing. We investigate the question of frequency of playing. The TP was measured with Zimbardo's TP Inventory (ZTPI), which includes five factors-past negative, past positive, present hedonistic, present fatalistic, and future. The study used data from 154 MMORPG players. We demonstrated that TP partially explained differences within a group of players with respect to the frequency of playing. Significant positive correlations were found between present factors and the amount of time spent playing MMORPGs, and significant negative correlation was found between the future factor and the time spent playing MMORPGs. Our study also revealed the influence of future-present balance on playing time. Players who scored lower in future-present balance variables (their present score was relatively high compared with their future score) reported higher values in playing time. In contrast to referential studies on TP and drug abuse and gambling, present fatalistic TP was demonstrated to be a stronger predictor of extensive playing than present hedonistic TP, which opened the question of motivation for playing. The advantage of our study compared with other personality-based studies lies in the fact that TP is a stable but malleable personality trait with a direct link to playing behavior. Therefore, TP is a promising conceptual resource for excessive playing therapy.

Interrelationship between TP53 gene deletion, protein expression and chromosome 17 aneusomy in gastric adenocarcinoma

PubMed Central

2009-01-01

Background This study evaluates the existence of numerical alterations of chromosome 17 and TP53 gene deletion in gastric adenocarcinoma. The p53 protein expression was also evaluated, as well as, possible associations with clinicopathological characteristics. Methods Dual-color fluorescence in situ hybridization and immunostaining were performed in twenty gastric cancer samples of individuals from Northern Brazil. Results Deletion of TP53 was found in all samples. TP53 was inactivated mainly by single allelic deletion, varying to 7–39% of cells/case. Aneusomy of chromosome 17 was observed in 85% of cases. Chromosome 17 monosomy and gain were both observed in about half of cases. Cells with gain of chromosome 17 frequently presented TP53 deletion. The frequency of cells with two chr17 and one TP53 signals observed was higher in diffuse than in intestinal-type GC. Immunoreactivity of p53 was found only in intestinal-type samples. The frequency of cells with two chr17 and two TP53 signals found was higher in samples with positive p53 expression than in negative cases in intestinal-type GC. Conclusion We suggest that TP53 deletion and chromosome 17 aneusomy is a common event in GC and other TP53 alterations, as mutation, may be implicated in the distinct carcinogenesis process of diffuse and intestinal types. PMID:19619279

Comparison of urologist reimbursement for managing patients with low-risk prostate cancer by active surveillance versus total prostatectomy.

PubMed

Manoharan, M; Eldefrawy, A; Katkoori, D; Antebi, E; Soloway, M S

2010-12-01

Active surveillance (AS) is an alternative to total prostatectomy (TP) in managing low-risk prostate cancer (PC). Our aim is to compare urologist reimbursement for managing low-risk PC by AS or TP. The urologist's reimbursement for TP includes the fee for the procedure and follow-up visits. For AS, our protocol involves digital rectal examination (DRE) and PSA testing every 3 months for first 2 years and every 6 months thereafter. Transrectal ultrasound (TRUS)-guided biopsies are performed yearly. Some urologists recommend spacing the biopsies by 1-3 years. Medicare reimbursement values were used. The urologist reimbursements for a follow-up visit, prostate biopsy, open TP and robotic TP are $72, $595, $1905 and $2939, respectively. We also corrected for a 15% chance of having TP after being on AS. The cumulative reimbursements from open TP and following the patient up to 10 years are approximately $2121 (1 year), $2265 (2 years), $2697 (5 years) and $3057 (10 years). For robotic TP, the urologist reimbursements are $3155 (1 year), $3259 (2 years), $3731 (5 years) and $4091 (10 years). For AS, the urologist reimbursements are $883 (1 year), $1766 (2 years), $4269 (5 years) and $7964 (10 years). The urologist reimbursement from AS and TP become nearly equal between 3 and 4 years follow-up, subsequently AS attains higher reimbursement.

A Comparison of Taped Problems with and without a Brief Post-Treatment Assessment on Multiplication Fluency

ERIC Educational Resources Information Center

Bliss, Stacy L.; Skinner, Christopher H.; McCallum, Elizabeth; Saecker, Lee B.; Rowland-Bryant, Emily; Brown, Katie S.

2010-01-01

An adapted alternating treatments design was used to compare the effectiveness of a taped-problems (TP) intervention with TP and an additional immediate assessment (TP + AIA) on the multiplication fluency of six fifth-grade students. During TP, the students listened to a tape playing a series of multiplication problems and answers three times.…

7-Hydroxystaurosporine (UCN-01) preferentially sensitizes cells with a disrupted TP53 to gamma radiation in lung cancer cell lines.

PubMed

Xiao, Helen H; Makeyev, Yan; Butler, James; Vikram, Bhadrasain; Franklin, William A

2002-07-01

Mutations in TP53 occur in more than 50% of the lung cancer patients and are associated with an increased resistance to chemotherapy and radiotherapy. The human lung adenocarcinoma cell lines A549 and LXSN contain a wild-type TP53 and were growth arrested at both the G(1)- and G(2)-phase checkpoints after irradiation. However, a TP53-disrupted cell line, E6, was arrested only at the G(2)-phase checkpoint. UCN-01 (7-hydroxystaurosporine), a CHEK1 inhibitor that abrogates the G(2) block, has been reported to enhance radiation toxicity in human lymphoma and colon cancer cell lines. In this study, UCN-01 preferentially enhanced the radiosensitivity of the TP53-disrupted E6 cells compared to the TP53 wild-type cells. This effect was more pronounced in cells synchronized in early G(1) phase, where the E6 cells showed a higher resistance to radiation in the absence of drug. These results indicate that the combination of UCN-01 and radiation can more specifically target resistant TP53 mutated cancer cells and spare TP53 wild-type normal cells.

Crystal growth of triphenylphosphine oxide 4-nitrophenol (TP4N) for nonlinear optical (NLO) applications

NASA Astrophysics Data System (ADS)

Pandian, Muthu Senthil; Karuppasamy, P.; Kamalesh, T.; Ramasamy, P.; Verma, Sunil

2018-04-01

The optically good quality organic single crystals of triphenylphosphine oxide 4-nitrophenol (TP4N) were successfully grown by slow evaporation solution technique (SEST) using methanol as solvent. The lattice parameters of the grown crystal were confirmed by single crystal X-ray diffraction analysis. The optical transmittance, cut-off wavelength and band gap of the TP4N crystal were obtained by UV-Vis NIR spectrum analysis. The photoluminescence studies were carried out to find out the luminesce properties of TP4N single crystal. The photoconductivity studies reveal that the TP4N crystal has negative photoconductive nature. The third order nonlinear susceptibility (χ(3)) of TP4N crystal was evaluated using the Z-scan technique at 640 nm.

A polymorphism (rs1042522) in TP53 gene is a risk factor for Down Syndrome in Sicilian mothers.

PubMed

Salemi, Michele; Barone, Concetta; Salluzzo, Maria Grazia; Giambirtone, Mariaconcetta; Scillato, Francesco; Galati Rando, Rosanna; Romano, Carmelo; Morale, Maria Concetta; Ridolfo, Federico; Romano, Corrado

2017-11-01

Trisomy 21 is the most frequent genetic cause of intellectual disability. Tumor Protein 53 (TP53) gene down-regulation triggers chromosomal instability. A TP53 gene polymorphism c.215G > C (rs1042522) is associated with accumulation of aneuploid cells. We analyzed the TP53 c.215G > C (rs1042522) polymorphism in Sicilian mothers of subjects with Down Syndrome (DS) within a case-control study. Nucleotide polymorphism was detected by pyrosequencing technology. The distribution of TP53 c.215G > C polymorphism showed significant difference between mothers of subjects with DS and controls. Our data show that TP53 c.215G > C polymorphism is a risk factor for DS in Sicilian mothers.

Construction of halide-bridged tungsten-copper-sulfide double cubanelike clusters from a new precursor [(Tp*WS2)2(μ-S2)].

PubMed

Wei, Li-Pei; Ren, Zhi-Gang; Zhu, Lian-Wen; Yan, Wen-Yan; Sun, Sha; Wang, Hui-Fang; Lang, Jian-Ping; Sun, Zhen-Rong

2011-05-16

Treatment of [Et(4)N][Tp*WS(3)] (1) (Tp* = hydridotris(3,5-dimethylpyrazol-1-yl)borate) with 2 equiv of AgSCN in MeCN afforded a novel neutral compound [(Tp*WS(2))(2)(μ-S(2))] (2). Reactions of 2 with excess CuX (X = Cl, Br, I) in MeCN and CH(2)Cl(2) or CHCl(3) formed three neutral W/Cu/S clusters [{Tp*W(μ(3)-S)(3)Cu(3)(μ-Cl)}(2)Cu(μ-Cl)(2)(μ(7)-Cl)(MeCN)](2) (3), [{Tp*W(μ(3)-S)(3)Cu(3)}(2)Br(μ-Br)(2)(μ(4)-Br)(MeCN)] (4), and [{Tp*W(μ(3)-S)(3)Cu(3)}(2){Cu(2)(μ-I)(4)(μ(3)-I)(2)}] (5), respectively. On the other hand, treatment of 2 with CuX (X = Cl, Br) in the presence of Et(4)NX (X = Cl, Br) produced two anionic W/Cu/S clusters [Et(4)N][{Tp*W(μ(3)-S)(3)Cu(3)X}(2)(μ-X)(2)(μ(4)-X)] (6: X = Cl; 7 X = Br). Compounds 2-7 were characterized by elemental analysis, IR, UV-vis, (1)H NMR, electrospray ionization (ESI) mass spectra, and single-crystal X-ray crystallography. The dimeric structure of 2 can be viewed as two [Tp*WS(2)] fragments in which two W atoms are connected by one S(2)(2-) dianion. Compounds 3-7 all possess unique halide-bridged double cubanelike frameworks. For 3, two [Tp*W(μ(3)-S)(3)Cu(3)](2+) dications are linked via a μ(7)-Cl(-) bridge, two μ-Cl(-) bridges, and a [Cu(MeCN)(μ-Cl)(2)](+) bridge. For 4, one [Tp*W(μ(3)-S)(3)Cu(3)(MeCN)](2+) dication and one [Tp*W(μ(3)-S)(3)Cu(3)Br](+) cation are linked via a μ(4)-Br(-) and two μ-Br(-) bridges. For 5, the two [Tp*W(μ(3)-S)(3)Cu(3)](2+) dications are bridged by a linear [(μ-I)(2)Cu(μ(3)-I)(2)Cu(μ-I)(2)](4+) species. For 6 and 7, two [Tp*W(μ(3)-S)(3)Cu(3)X](+) cations are linked by a μ(4)-X(-) and two μ-X(-) bridges (X = Cl, Br). In addition, the third-order nonlinear optical (NLO) properties of 2-7 in MeCN/CH(2)Cl(2) were investigated by using femtosecond degenerate four-wave mixing (DFWM) technique.

Analysis of full coding sequence of the TP53 gene in invasive vulvar cancers: Implications for therapy.

PubMed

Kashofer, Karl; Regauer, Sigrid

2017-08-01

This study evaluates the frequency and type of TP53 gene mutations and HPV status in 72 consecutively diagnosed primary invasive vulvar squamous cell carcinomas (SCC) during the past 5years. DNA of formalin-fixed and paraffin embedded tumour tissue was analysed for 32 HPV subtypes and the full coding sequence of the TP53 gene, and correlated with results of p53 immunohistochemistry. 13/72 (18%) cancers were HPV-induced squamous cell carcinomas, of which 1/13 (8%) carcinoma harboured a somatic TP53 mutation. Among the 59/72 (82%) HPV-negative cancers, 59/72 (82%) SCC were HPV-negative with wild-type gene in 14/59 (24%) SCC and somatic TP53 mutations in 45/59 (76%) SCC. 28/45 (62%) SCC carried one (n=20) or two (n=8) missense mutations. 11/45 (24%) carcinomas showed a single disruptive mutation (3× frame shift, 7× stop codon, 1× deletion), 3/45 SCC a splice site mutation. 3/45 (7%) carcinomas had 2 or 3 different mutations. 18 different "hot spot" mutations were observed in 22/45 cancers (49%; 5× R273, 3× R282; 2× each Y220, R278, R248). Immunohistochemical p53 over expression was identified in most SCC with missense mutations, but not in SCC with disruptive TP53 mutations or TP53 wild-type. 14/45 (31%) patients with TP53 mutated SCC died of disease within 12months (range 2-24months) versus 0/13 patients with HPV-induced carcinomas and 0/14 patients with HPV-negative, TP53 wild-type carcinomas. 80% of primary invasive vulvar SCC were HPV-negative carcinomas with a high frequency of disruptive mutations and "hot spot" TP53 gene mutations, which have been linked to chemo- and radioresistance. The death rate of patients with p53 mutated vulvar cancers was 31%. Immunohistochemical p53 over expression could not reliably identify SCC with TP53 gene mutation. Pharmacological therapies targeting mutant p53 will be promising strategies for personalized therapy in patients with TP53 mutated vulvar cancers. Copyright © 2017. Published by Elsevier Inc.

The pancreas is altered by in utero androgen exposure: implications for clinical conditions such as polycystic ovary syndrome (PCOS).

PubMed

Rae, Mick; Grace, Cathal; Hogg, Kirsten; Wilson, Lisa Marie; McHaffie, Sophie L; Ramaswamy, Seshadri; MacCallum, Janis; Connolly, Fiona; McNeilly, Alan S; Duncan, Colin

2013-01-01

Using an ovine model of polycystic ovary syndrome (PCOS), (pregnant ewes injected with testosterone propionate (TP) (100 mg twice weekly) from day (d)62 to d102 of d147 gestation (maternal injection - MI-TP)), we previously reported female offspring with normal glucose tolerance but hyperinsulinemia. We therefore examined insulin signalling and pancreatic morphology in these offspring using quantitative (Q) RT-PCR and western blotting. In addition the fetal pancreatic responses to MI-TP, and androgenic and estrogenic contributions to such responses (direct fetal injection (FI) of TP (20 mg) or diethylstilbestrol (DES) (20 mg) at d62 and d82 gestation) were assessed at d90 gestation. Fetal plasma was assayed for insulin, testosterone and estradiol, pancreatic tissue was cultured, and expression of key β-cell developmental genes was assessed by QRT-PCR. In female d62MI-TP offspring insulin signalling was unaltered but there was a pancreatic phenotype with increased numbers of β-cells (P<0.05). The fetal pancreas expressed androgen receptors in islets and genes involved in β-cell development and function (PDX1, IGF1R, INSR and INS) were up-regulated in female fetuses after d62MI-TP treatment (P<0.05-0.01). In addition the d62MI-TP pancreas showed increased insulin secretion under euglycaemic conditions (P<0.05) in vitro. The same effects were not seen in the male fetal pancreas or when MI-TP was started at d30, before the male programming window. As d62MI-TP increased both fetal plasma testosterone (P<0.05) and estradiol concentrations (P<0.05) we assessed the relative contribution of androgens and estrogens. FI-TP (commencing d62) (not FI-DES treatment) caused elevated basal insulin secretion in vitro and the genes altered by d62MI-TP treatment were similarly altered by FI-TP but not FI-DES. In conclusion, androgen over-exposure alters fetal pancreatic development and β-cell numbers in offspring. These data suggest that that there may be a primary pancreatic phenotype in models of PCOS, and that there may be a distinct male and female pancreas.

Aspirin Is Associated with Improved Survival in Severely Thrombocytopenic Cancer Patients with Acute Myocardial Infarction.

PubMed

Feher, Attila; Kampaktsis, Polydoros N; Parameswaran, Rekha; Stein, Eytan M; Steingart, Richard; Gupta, Dipti

2017-02-01

Patients with hematologic malignancies are at risk for severe thrombocytopenia (sTP). The risk and benefit of aspirin are not known in thrombocytopenic cancer patients experiencing acute myocardial infarction (AMI). Medical records of patients with hematologic malignancies diagnosed with AMI at Memorial Sloan Kettering Cancer Center during 2005-2014 were reviewed. sTP was defined as a platelet count <50,000 cells per µL within 7 days of AMI. Of 118 patients with hematologic malignancies who had AMI, 58 (49%) had sTP. Twenty-five patients (43%) with sTP received aspirin as a treatment for AMI. Compared with patients without sTP with AMI, patients with sTP with AMI were less likely to receive aspirin (83% vs. 43%; p  = .0001) and thienopyridine treatment (27% vs. 3%; p  = .0005). During median follow-up of 3.7 years after AMI, survival was lower in patients with sTP than in those with no sTP (23% vs. 50% at 1 year; log rank p  = .003). Patients with sTP who received aspirin for AMI had improved survival compared with those who did not (92% vs. 70% at 7 days, 72% vs. 33% at 30 days, and 32% vs. 13% at 1 year; log rank p  = .008). In multivariate regression models, aspirin use was associated with improved 30-day survival both in the overall patient cohort and in sTP patients. No fatal bleeding events occurred. Major bleeding was not associated with sTP or aspirin use. Treatment of AMI with aspirin in patients with hematologic malignancies and sTP is associated with improved survival without increase in major bleeding. The Oncologist 2017;22:213-221 Implications for Practice: In patients with hematologic malignancies and acute myocardial infarction with severe thrombocytopenia (platelet count < 50,000 cells/µL), guideline-recommended medical therapy is often withheld because of the fear of major bleeding. In this study, aspirin therapy was associated with improved survival without an increase in major bleeding in this high-risk patient cohort. © AlphaMed Press 2017.

Characterization of proopiomelanocortin in the snakeskin gourami (Trichopodus pectoralis) and its expression in relation to food intake.

PubMed

Boonanuntanasarn, S; Jangprai, A; Yoshizaki, G

2015-01-01

Proopiomelanocortin (POMC) is the precursor of several hormones involved in physiological systems including feed intake. The snakeskin gourami (Trichopodus pectoralis) POMC complementary DNA (TpPOMC) was cloned and characterized. Phylogenetic analysis showed that TpPOMC was clustered in a major POMC lineage in fish. Analysis of the Ka to Ks ratios for the entire POMC sequence and for each hormonal segment suggested that different POMC-derived peptide segments were subject to different evolutionary pressures. High expression level of TpPOMC was observed in all brain regions, with the highest levels in the diencephalon and pituitary gland. In situ hybridization also revealed that TpPOMC-expressing cells were distributed in discrete brain regions. The transcription level of TpPOMC was also found at moderate levels in several peripheral tissues, including gills, liver, head kidney, trunk kidney, stomach, intestine, spleen, ovary and testis, and at a low level in muscle. The expression level of TpPOMC was evaluated in each brain region (telencephalon, mesencephalon, metencephalon, and diencephalon together with the pituitary gland) at 1 h before the first and the last meals of the day and compared with expression levels at a time interval between the first and the last meals of the day. Low expression levels of TpPOMC were found at 1 h before the last meal of the day (P < 0.05). These finding suggest that decreased POMC expression level may lead to reduced melanocyte-stimulating hormones, which may in part be responsible for stimulating food intake. The effect of short-term fasting (24 h) on TpPOMC expression level in each brain region was also investigated. In telencephalon and diencephalon together with the pituitary gland, TpPOMC messenger RNA reached a nadir at 12 h of fasting, whereas TpPOMC transcript showed a nadir at 6 h of fasting in metencephalon and mesencephalon. A peak of TpPOMC level was observed at 18 h of fasting in metencephalon and diencephalon together with the pituitary gland. These findings suggest that TpPOMC expression is affected by nutritional status. Copyright © 2015 Elsevier Inc. All rights reserved.

Marathon Kids UK: study design and protocol for a mixed methods evaluation of a school-based running programme

PubMed Central

Routen, Ash C; Harris, Jo P; Cale, Lorraine A; Gorely, Trish; Sherar, Lauren B

2018-01-01

Introduction Schools are promising settings for physical activity promotion; however, they are complex and adaptive systems that can influence the quality of programme implementation. This paper presents an evaluation of a school-based running programme (Marathon Kids). The aims of this study are (1) to identify the processes by which schools implement the programme, (2) identify and explain the contextual factors affecting implementation and explications of effectiveness and (3) examine the relationship between the level of implementation and perceived outcomes. Methods Using a realist evaluation framework, a mixed method single-group before-and-after design, strengthened by multiple interim measurements, will be used. Year 5 (9–10 years old) pupils and their teachers will be recruited from six state-funded primary schools in Leicestershire, UK. Data will be collected once prior to implementation, at five discrete time points during implementation and twice following implementation. A weekly implementation log will also be used. At time point 1 (TP1) (September 2016), data on school environment, teacher and pupil characteristics will be collected. At TP1 and TP6 (July 2017), accelerometry, pupil self-reported physical activity and psychosocial data (eg, social support and intention to be active) will be collected. At TP2, TP3 and TP5 (January, March and June 2017), observations will be conducted. At TP2 and TP5, there will be teacher interviews and pupil focus groups. Follow-up teacher interviews will be conducted at TP7 and TP8 (October 2017 and March 2018) and pupil focus group at TP8. In addition, synthesised member checking will be conducted (June 2018) with a mixed sample of schools. Ethics and dissemination Ethical approval for this study was obtained through Loughborough University Human Participants Ethics Subcommittee (R16-P032 & R16-P116). Findings will be disseminated via print, online media and dissemination events as well as practitioner and/or research journals. PMID:29764890

Steric and electronic effects on arylthiolate coordination in the pseudotetrahedral complexes [(Tp(Ph,Me))Ni-SAr] (Tp(Ph,Me) = hydrotris{3-phenyl-5-methyl-1-pyrazolyl}borate).

PubMed

Deb, Tapash; Anderson, Caitlin M; Chattopadhyay, Swarup; Ma, Huaibo; Young, Victor G; Jensen, Michael P

2014-12-14

Synthesis and characterization of several new pseudotetrahedral arylthiolate complexes [(Tp(Ph,Me))Ni-SAr] (Tp(Ph,Me) = hydrotris{3-phenyl-5-methyl-1-pyrazolyl}borate; Ar = Ph, 2,4,6-(i)Pr3C6H2, C6H4-4-Cl, C6H4-4-Me, C6H4-4-OMe) are reported, including X-ray crystal structures of the first two complexes. With prior results, two series of complexes are spanned, [(Tp(Ph,Me))Ni-S-2,4,6-RC6H2] (R'' = H, Me, (i)Pr) plus the xylyl analogue [(Tp(Ph,Me))Ni-S-2,6-Me2C6H3], as well as [(Tp(Ph,Me))Ni-S-C6H4-4-Y] (Y = Cl, H, Me, OMe), intended to elucidate steric and/or electronic effects on arylthiolate coordination. In contrast to [(Tp(Me,Me))Ni-SAr] analogues that adopt a sawhorse conformation, the ortho-disubstituted complexes show enhanced trigonal and Ni-S-Ar bending, reflecting the size of the 3-pyrazole substituents. Moreover, weakened scorpionate ligation is implied by spectroscopic data. Little spectroscopic effect is observed in the series of para-substituted complexes, suggesting the observed effects are primarily steric in origin. The relatively electron-rich and encumbered complex [(Tp(Ph,Me))Ni-S-2,4,6-(i)Pr3C6H2] behaves uniquely when dissolved in CH3CN, forming a square planar solvent adduct with a bidentate scorpionate ligand, [(κ(2)-Tp(Ph,Me))Ni(NCMe)(S-2,4,6-(i)Pr3C6H2)]. This adduct was isolated and characterized by X-ray crystallography. Single-point DFT and TD-DFT calculations on a simplified [(κ(2)-Tp)Ni(NCMe)(SPh)] model were used to clarify the electronic spectrum of the adduct, and to elucidate differences between Ni-SAr bonding and spectroscopy between pseudotetrahedral and square planar geometries.

Solid-state thermal behavior and stability studies of theophylline-citric acid cocrystals prepared by neat cogrinding or thermal treatment

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

Hsu, Po-Chun; Lin, Hong-Liang; Wang, Shun-Li, E-mail: wangshunli@mail.ncyu.edu.tw

To investigate the thermal behavior of cocrystal formed between anhydrous theophylline (TP) and anhydrous citric acid (CA) by neat manual cogrinding or thermal treatment, DSC and FTIR microspectroscopy with curve-fitting analysis were applied. The physical mixture and 60-min ground mixture were stored at 55{+-}0.5 Degree-Sign C/40{+-}2% RH condition to determine their stability behavior. Typical TP-CA cocrystals were prepared by slow solvent evaporation method. Results indicate that the cogrinding process could gradually induce the cocrystal formation between TP and CA. The IR spectral peak shift from 3495 to 3512 cm{sup -1} and the stepwise appearance of several new IR peaks atmore » 1731, 1712, 1676, 1651, 1557 and 1265 cm{sup -1} with cogrinding time suggest that the mechanism of TP-CA cocrystal formation was evidenced by interacting TP with CA through the intermolecular O-H{center_dot}{center_dot}{center_dot}O hydrogen bonding. The stability of 60-min ground mixture of TP-CA was confirmed at 55{+-}0.5 Degree-Sign C/40{+-}2% RH condition over a storage time of 60 days. - Garphical abstract: Cogrinding, thermal and solvent-evaporation methods might easily induce the theophylline-citric acid cocrystal formation. Highlights: Black-Right-Pointing-Pointer Cogrinding process could gradually induce the cocrystal formation between TP and CA. Black-Right-Pointing-Pointer The TP-CA cocrystal was formed through the intermolecular O-H{center_dot}{center_dot}{center_dot}O hydrogen bonding. Black-Right-Pointing-Pointer The 60-min TP-CA ground mixture was similar to the solvent-evaporated cocrystal. Black-Right-Pointing-Pointer The thermal-induced TP-CA cocrystal formation was confirmed by pre-heating the physical mixture to 152 Degree-Sign C. Black-Right-Pointing-Pointer The 60-min TP-CA ground mixture was stable at accelerated condition over a storage time of 60 days.« less

TP53 alterations in Wilms tumour represent progression events with strong intratumour heterogeneity that are closely linked but not limited to anaplasia.

PubMed

Wegert, Jenny; Vokuhl, Christian; Ziegler, Barbara; Ernestus, Karen; Leuschner, Ivo; Furtwängler, Rhoikos; Graf, Norbert; Gessler, Manfred

2017-10-01

TP53 mutations have been associated with anaplasia in Wilms tumour, which conveys a high risk for relapse and fatal outcome. Nevertheless, TP53 alterations have been reported in no more than 60% of anaplastic tumours, and recent data have suggested their presence in tumours that do not fulfil the criteria for anaplasia, questioning the clinical utility of TP53 analysis. Therefore, we characterized the TP53 status in 84 fatal cases of Wilms tumour, irrespective of histological subtype. We identified TP53 alterations in at least 90% of fatal cases of anaplastic Wilms tumour, and even more when diffuse anaplasia was present, indicating a very strong if not absolute coupling between anaplasia and deregulation of p53 function. Unfortunately, TP53 mutations do not provide additional predictive value in anaplastic tumours since the same mutation rate was found in a cohort of non-fatal anaplastic tumours. When classified according to tumour stage, patients with stage I diffuse anaplastic tumours still had a high chance of survival (87%), but this rate dropped to 26% for stages II-IV. Thus, volume of anaplasia or possible spread may turn out to be critical parameters. Importantly, among non-anaplastic fatal tumours, 26% had TP53 alterations, indicating that TP53 screening may identify additional cases at risk. Several of these non-anaplastic tumours fulfilled some criteria for anaplasia, for example nuclear unrest, suggesting that such partial phenotypes should be under special scrutiny to enhance detection of high-risk tumours via TP53 screening. A major drawback is that these alterations are secondary changes that occur only later in tumour development, leading to striking intratumour heterogeneity that requires multiple biopsies and analysis guided by histological criteria. In conclusion, we found a very close correlation between histological signs of anaplasia and TP53 alterations. The latter may precede development of anaplasia and thereby provide diagnostic value pointing towards aggressive disease.

TP53 alterations in Wilms tumour represent progression events with strong intratumour heterogeneity that are closely linked but not limited to anaplasia

PubMed Central

Wegert, Jenny; Vokuhl, Christian; Ziegler, Barbara; Ernestus, Karen; Leuschner, Ivo; Furtwängler, Rhoikos; Graf, Norbert

2017-01-01

Abstract TP53 mutations have been associated with anaplasia in Wilms tumour, which conveys a high risk for relapse and fatal outcome. Nevertheless, TP53 alterations have been reported in no more than 60% of anaplastic tumours, and recent data have suggested their presence in tumours that do not fulfil the criteria for anaplasia, questioning the clinical utility of TP53 analysis. Therefore, we characterized the TP53 status in 84 fatal cases of Wilms tumour, irrespective of histological subtype. We identified TP53 alterations in at least 90% of fatal cases of anaplastic Wilms tumour, and even more when diffuse anaplasia was present, indicating a very strong if not absolute coupling between anaplasia and deregulation of p53 function. Unfortunately, TP53 mutations do not provide additional predictive value in anaplastic tumours since the same mutation rate was found in a cohort of non‐fatal anaplastic tumours. When classified according to tumour stage, patients with stage I diffuse anaplastic tumours still had a high chance of survival (87%), but this rate dropped to 26% for stages II–IV. Thus, volume of anaplasia or possible spread may turn out to be critical parameters. Importantly, among non‐anaplastic fatal tumours, 26% had TP53 alterations, indicating that TP53 screening may identify additional cases at risk. Several of these non‐anaplastic tumours fulfilled some criteria for anaplasia, for example nuclear unrest, suggesting that such partial phenotypes should be under special scrutiny to enhance detection of high‐risk tumours via TP53 screening. A major drawback is that these alterations are secondary changes that occur only later in tumour development, leading to striking intratumour heterogeneity that requires multiple biopsies and analysis guided by histological criteria. In conclusion, we found a very close correlation between histological signs of anaplasia and TP53 alterations. The latter may precede development of anaplasia and thereby provide diagnostic value pointing towards aggressive disease. PMID:29085664

Electrode spanning with partial tripolar stimulation mode in cochlear implants.

PubMed

Wu, Ching-Chih; Luo, Xin

2014-12-01

The perceptual effects of electrode spanning (i.e., the use of nonadjacent return electrodes) in partial tripolar (pTP) mode were tested on a main electrode EL8 in five cochlear implant (CI) users. Current focusing was controlled by σ (the ratio of current returned within the cochlea), and current steering was controlled by α (the ratio of current returned to the basal electrode). Experiment 1 tested whether asymmetric spanning with α = 0.5 can create additional channels around standard pTP stimuli. It was found that in general, apical spanning (i.e., returning current to EL6 rather than EL7) elicited a pitch between those of standard pTP stimuli on main electrodes EL8 and EL9, while basal spanning (i.e., returning current to EL10 rather than EL9) elicited a pitch between those of standard pTP stimuli on main electrodes EL7 and EL8. The pitch increase caused by apical spanning was more salient than the pitch decrease caused by basal spanning. To replace the standard pTP channel on the main electrode EL8 when EL7 or EL9 is defective, experiment 2 tested asymmetrically spanned pTP stimuli with various α, and experiment 3 tested symmetrically spanned pTP stimuli with various σ. The results showed that pitch increased with decreasing α in asymmetric spanning, or with increasing σ in symmetric spanning. Apical spanning with α around 0.69 and basal spanning with α around 0.38 may both elicit a similar pitch as the standard pTP stimulus. With the same σ, the symmetrically spanned pTP stimulus was higher in pitch than the standard pTP stimulus. A smaller σ was thus required for symmetric spanning to match the pitch of the standard pTP stimulus. In summary, electrode spanning is an effective field-shaping technique that is useful for adding spectral channels and handling defective electrodes with CIs.

Effect of residential development on stream phosphorus dynamics in headwater suburbanizing watersheds of southern Ontario, Canada.

PubMed

Duval, Tim P

2018-10-01

Suburban landscapes are known to have degraded water quality relative to natural settings, including increased total phosphorus (TP) levels; however, the effect of subdivision construction activities on stream TP dynamics are less understood. This study measured TP and its constituents particulate, dissolved organic, and dissolved inorganic phosphorus (PP, DOP, and DIP, respectively) in two headwater streams of contrasting urbanization activity to examine whether the land-use conversion process itself contributed to TP concentrations and export. The nested watershed undergoing significant active residential community construction contained large areas of cleared former agricultural field and associated sediment mounds with elevated soil TP (~1000 mg kg -1 ), and twice as many stormwater management (SWM) ponds than the watershed with completed suburban communities. Daily stream sampling for six months revealed limited differences in TP between urbanized and urbanizing watersheds regardless of season or stream flow condition; however, the forms of TP varied significantly. The proportion of TP as DOP was consistently higher in the urbanizing stream relative to the urban stream, which was in line with significant decreases in DOP concentration as proportion of cleared former agricultural land decreased and density of SWM ponds increased. The DOP, and to a lesser extent DIP and PP, dynamics resulted in a 2.5× greater areal export of TP from a small watershed actively being suburbanized during the study period compared to the larger watershed with greater land urbanized 3-5 years ago. The results of this study suggest stream TP concentrations are relatively unresponsive to active versus established suburban cover, but the forms of TP can be quite different, and the period of home construction can increase phosphorus (P) delivery to and export through nearby streams. This information can aid land managers and urban planners update best management practices to mitigate the transfer of terrestrial P to the aquatic environment. Copyright © 2018 Elsevier B.V. All rights reserved.

Influence of carbon nanotubes on the properties of epoxy based composites reinforced with a semicrystalline thermoplastic

NASA Astrophysics Data System (ADS)

Díez-Pascual, A.; Shuttleworth, P.; Gónzalez-Castillo, E.; Marco, C.; Gómez-Fatou, M.; Ellis, G.

2014-08-01

Novel ternary nanocomposites based on a thermoset (TS) system composed of triglycidyl p-aminophenol (TGAP) epoxy resin and 4,4'-diaminodiphenylsulfone (DDS) curing agent incorporating 5 wt% of a semicrystalline thermoplastic (TP), an ethylene/1-octene copolymer, and 0.5 or 1.0 wt% multi-walled carbon nanotubes (MWCNTs) have been prepared via physical blending and curing. The influence of the TP and the MWCNTs on the curing process, morphology, thermal and mechanical properties of the hybrid nanocomposites has been analyzed. Different morphologies evolved depending on the CNT content: the material with 0.5 wt% MWCNTs showed a matrix-dispersed droplet-like morphology with well-dispersed nanofiller that selectively located at the TS/TP interphase, while that with 1.0 wt% MWCNTs exhibited coarse dendritic TP areas containing agglomerated MWCNTs. Although the cure reaction was accelerated in its early stage by the nanofillers, curing occurred at a lower rate since these obstructed chain crosslinking. The nanocomposite with lower nanotube content displayed two crystallization peaks at lower temperature than that of pure TP, while a single peak appearing at similar temperature to that of TP was observed for the blend with higher nanotube loading. The highest thermal stability was found for TS/TP (5.0 wt%)/MWCNTs (0.5 wt%), due to a synergistic barrier effect of both TP and the nanofiller. Moreover, this nanocomposite displayed the best mechanical properties, with an optimal combination of stiffness, strength and toughness. However, poorer performance was found for TS/TP (5.0 wt%)/MWCNTs (1.0 wt%) due to the less effective reinforcement of the agglomerated nanotubes and the coalescence of the TP particles into large areas. Therefore, finely tuned morphologies and properties can be obtained by adjusting the nanotube content in the TS/TP blends, leading to high-performance hybrid nanocomposites suitable for structural and high-temperature applications.

Parametrial adipose tissue and metabolic dysfunctions induced by fructose-rich diet in normal and neonatal-androgenized adult female rats.

PubMed

Alzamendi, Ana; Castrogiovanni, Daniel; Ortega, Hugo H; Gaillard, Rolf C; Giovambattista, Andres; Spinedi, Eduardo

2010-03-01

Hyperandrogenemia predisposes an organism toward developing impaired insulin sensitivity. The aim of our study was to evaluate endocrine and metabolic effects during early allostasis induced by a fructose-rich diet (FRD) in normal (control; CT) and neonatal-androgenized (testosterone propionate; TP) female adult rats. CT and TP rats were fed either a normal diet (ND) or an FRD for 3 weeks immediately before the day of study, which was at age 100 days. Energy intake, body weight (BW), parametrial (PM) fat characteristics, and endocrine/metabolic biomarkers were then evaluated. Daily energy intake was similar in CT and TP rats regardless of the differences in diet. When compared with CT-ND rats, the TP-ND rats were heavier, had larger PM fat, and were characterized by basal hypoadiponectinemia and enhanced plasma levels of non-esterified fatty acid (NEFA), plasminogen activator inhibitor-1 (PAI-1), and leptin. FRD-fed CT rats, when compared with CT-ND rats, had high plasma levels of NEFA, triglyceride (TG), PAI-1, leptin, and adiponectin. The TP-FRD rats, when compared with TP-ND rats, displayed enhanced leptinemia and triglyceridemia, and were hyperinsulinemic, with glucose intolerance. The PM fat taken from TP rats displayed increase in the size of adipocytes, decrease in adiponectin (protein/gene), and a greater abundance of the leptin gene. PM adipocyte response to insulin was impaired in CT-FRD, TP-ND, and TP-FRD rats. A very short duration of isocaloric FRD intake in TP rats induced severe metabolic dysfunction at the reproductive age. Our study supports the hypothesis that the early-androgenized female rat phenotype is highly susceptible to developing endocrine/metabolic dysfunction. In turn, these abnormalities enhance the risk of metabolic syndrome, obesity, type 2 diabetes, and cardiovascular disease.

The Fluorocycline TP-271 Is Efficacious in Models of Aerosolized Francisella tularensis SCHU S4 Infection in BALB/c Mice and Cynomolgus Macaques.

PubMed

Grossman, Trudy H; Anderson, Michael S; Christ, David; Gooldy, Melanie; Henning, Lisa N; Heine, Henry S; Kindt, M Victoria; Lin, Winston; Siefkas-Patterson, Kaylyn; Radcliff, Anne K; Tam, Vincent H; Sutcliffe, Joyce A

2017-08-01

TP-271 is a novel, fully synthetic fluorocycline in development for complicated bacterial respiratory infections. TP-271 was active in vitro against a panel of 29 Francisella tularensis isolates, showing MICs against 50% and 90% of isolates of 0.25 and 0.5 μg/ml, respectively. In a mouse model of inhalational tularemia, animals were exposed by aerosol to 91 to 283 50% lethal doses (LD 50 )/mouse of F. tularensis SCHU S4. Following 21 days of once-daily intraperitoneal dosing with TP-271 at 3, 6, 12, and 18 mg/kg of body weight/day, initiating at 24 h postchallenge, survival was 80%, 100%, 100%, and 100%, respectively. When treatment was initiated at 72 h postchallenge, survival was 89%, 100%, 100%, and 100% in the 3-, 6-, 12-, and 18-mg/kg/day TP-271 groups, respectively. No mice treated with the vehicle control survived. Surviving mice treated with TP-271 showed little to no relapse during 14 days posttreatment. In a nonhuman primate model of inhalational tularemia, cynomolgus macaques received an average aerosol exposure of 1,144 CFU of F. tularensis SCHU S4. Once-daily intravenous infusion with 1 or 3 mg/kg TP-271, or vehicle control, for 21 days was initiated within 6 h of confirmed fever. All animals treated with TP-271 survived to the end of the study, with no relapse during 14 days after the last treatment, whereas no vehicle control-treated animals survived. The protection and low relapse afforded by TP-271 treatment in these studies support continued investigation of TP-271 for use in the event of aerosolized exposure to F. tularensis . Copyright © 2017 American Society for Microbiology.

The Fluorocycline TP-271 Is Efficacious in Models of Aerosolized Francisella tularensis SCHU S4 Infection in BALB/c Mice and Cynomolgus Macaques

PubMed Central

Anderson, Michael S.; Christ, David; Gooldy, Melanie; Henning, Lisa N.; Heine, Henry S.; Kindt, M. Victoria; Lin, Winston; Siefkas-Patterson, Kaylyn; Radcliff, Anne K.; Tam, Vincent H.; Sutcliffe, Joyce A.

2017-01-01

ABSTRACT TP-271 is a novel, fully synthetic fluorocycline in development for complicated bacterial respiratory infections. TP-271 was active in vitro against a panel of 29 Francisella tularensis isolates, showing MICs against 50% and 90% of isolates of 0.25 and 0.5 μg/ml, respectively. In a mouse model of inhalational tularemia, animals were exposed by aerosol to 91 to 283 50% lethal doses (LD50)/mouse of F. tularensis SCHU S4. Following 21 days of once-daily intraperitoneal dosing with TP-271 at 3, 6, 12, and 18 mg/kg of body weight/day, initiating at 24 h postchallenge, survival was 80%, 100%, 100%, and 100%, respectively. When treatment was initiated at 72 h postchallenge, survival was 89%, 100%, 100%, and 100% in the 3-, 6-, 12-, and 18-mg/kg/day TP-271 groups, respectively. No mice treated with the vehicle control survived. Surviving mice treated with TP-271 showed little to no relapse during 14 days posttreatment. In a nonhuman primate model of inhalational tularemia, cynomolgus macaques received an average aerosol exposure of 1,144 CFU of F. tularensis SCHU S4. Once-daily intravenous infusion with 1 or 3 mg/kg TP-271, or vehicle control, for 21 days was initiated within 6 h of confirmed fever. All animals treated with TP-271 survived to the end of the study, with no relapse during 14 days after the last treatment, whereas no vehicle control-treated animals survived. The protection and low relapse afforded by TP-271 treatment in these studies support continued investigation of TP-271 for use in the event of aerosolized exposure to F. tularensis. PMID:28559261

Tension pneumocephalus following suboccipital sitting craniotomy in the pediatric population.

PubMed

Daszkiewicz, P; Dziedzic, D

Sitting craniotomy often results in entrapment of air in fluid-filled intracranial cavities. Gas under pressure exerts a deleterious effect on adjacent nervous tissue, resulting in clinical deterioration. To assess the incidence of tension pneumocephalus (TP) and to define risk factors associated therewith. Analysis included 100 consecutive patients (57 boys, 43 girls, mean age 9.7 y) undergoing suboccipital sitting craniotomy since 2012 to 2014. In our material (n=100) TP was seen in 7 cases, asymptomatic pneumocephalus (AP) in 77 and no pneumocephalus (NP) in 16. Tumor types encountered were typical for pediatric population. In the TP group (n=7) the ratio of low-grade to high-grade tumors was 5:2, in the AP group (n=77) 2:1 and in the NP group (n=16) 1:1. Preoperative hydrocephalus was present in 21 cases (21%, mean incidence), thereof 3 in the TP group (3/7; 42.8%), 12 in AP group (12/77; 15.5%) and 6 in the NP group (6/16; 37.5%). All TP patients received an emergency external drainage, thereof 4 required a permanent ventriculo-peritoneal shunt (57.1%), while AP and NP patients combined (n=93) required a permanent shunt in 4 cases only (4.3%). TP-associated morbidity (n=2) consisted in a significant deterioration of neurological condition. TP is a relatively rare but potentially serious complication of suboccipital sitting craniotomy. Risk factors for TP are low-grade tumor and pre-existing long-standing hydrocephalus. TP requires emergency decompression by temporary external drainage. TP patients significantly more often require a permanent CSF shunt. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

TP53 Mutational Status Is a Potential Marker for Risk Stratification in Wilms Tumour with Diffuse Anaplasia

PubMed Central

Chagtai, Tasnim; Popov, Sergey D.; Sebire, Neil J.; Vujanic, Gordan; Perlman, Elizabeth; Anderson, James R.; Grundy, Paul; Dome, Jeffrey S.; Pritchard-Jones, Kathy

2014-01-01

Purpose The presence of diffuse anaplasia in Wilms tumours (DAWT) is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whether TP53 mutational status confers additional prognostic information. Patients and Methods We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32) and gene expression (n = 36) arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling. Results From the 40 cases, 22 (55%) had TP53 mutations (2 detected only after deep-sequencing), 20 of which also had 17p loss (91%); 18 (45%) cases had no detectable mutation but three had 17p loss. Tumours with TP53 mutations and/or 17p loss (n = 25) had an increased risk of recurrence as a first event (p = 0.03, hazard ratio (HR), 3.89; 95% confidence interval (CI), 1.26–16.0) and death (p = 0.04, HR, 4.95; 95% CI, 1.36–31.7) compared to tumours lacking TP53 abnormalities. DAWT carrying TP53 mutations showed increased copy number alterations compared to those with wild-type, suggesting a more unstable genome (p = 0.03). These tumours showed deregulation of genes associated with cell cycle and DNA repair biological processes. Conclusion This study provides evidence that TP53 mutational analysis improves risk stratification in DAWT. This requires validation in an independent cohort before clinical use as a biomarker. PMID:25313908

TP53 mutational status is a potential marker for risk stratification in Wilms tumour with diffuse anaplasia.

PubMed

Maschietto, Mariana; Williams, Richard D; Chagtai, Tasnim; Popov, Sergey D; Sebire, Neil J; Vujanic, Gordan; Perlman, Elizabeth; Anderson, James R; Grundy, Paul; Dome, Jeffrey S; Pritchard-Jones, Kathy

2014-01-01

The presence of diffuse anaplasia in Wilms tumours (DAWT) is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whether TP53 mutational status confers additional prognostic information. We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32) and gene expression (n = 36) arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling. From the 40 cases, 22 (55%) had TP53 mutations (2 detected only after deep-sequencing), 20 of which also had 17p loss (91%); 18 (45%) cases had no detectable mutation but three had 17p loss. Tumours with TP53 mutations and/or 17p loss (n = 25) had an increased risk of recurrence as a first event (p = 0.03, hazard ratio (HR), 3.89; 95% confidence interval (CI), 1.26-16.0) and death (p = 0.04, HR, 4.95; 95% CI, 1.36-31.7) compared to tumours lacking TP53 abnormalities. DAWT carrying TP53 mutations showed increased copy number alterations compared to those with wild-type, suggesting a more unstable genome (p = 0.03). These tumours showed deregulation of genes associated with cell cycle and DNA repair biological processes. This study provides evidence that TP53 mutational analysis improves risk stratification in DAWT. This requires validation in an independent cohort before clinical use as a biomarker.

Enhancement of mitomycin C-induced cytotoxicity by curcumin results from down-regulation of MKK1/2-ERK1/2-mediated thymidine phosphorylase expression.

PubMed

Weng, Shao-Hsing; Tsai, Min-Shao; Chiu, Yu-Fan; Kuo, Ya-Hsun; Chen, Huang-Jen; Lin, Yun-Wei

2012-03-01

Curcumin (diferuloylmethane), a phenolic compound obtained from the rhizome of Curcuma longa, has been found to inhibit cell proliferation in various human cancer cell lines, including non-small cell lung cancer (NSCLC). Thymidine phosphorylase (TP) is considered an attractive therapeutic target, because increased TP expression can suppress cancer cell death induced by DNA-damaging agents. Mitomycin C (MMC), a chemotherapeutic agent used to treat NSCLC, inhibits tumour growth through DNA cross-linking and breaking. Whether MMC can affect TP expression in NSCLC is unknown. Therefore, in this study, we suggested that curcumin enhances the effects of MMC-mediated cytotoxicity by decreasing TP expression and ERK1/2 activation. Exposure of human NSCLC cell lines H1975 and H1650 to curcumin decreased MMC-elicited phosphorylated MKK1/2-ERK1/2 protein levels. Moreover, curcumin significantly decreased MMC-induced TP protein levels by increasing TP mRNA and protein instability. Enhancement of ERK1/2 activation by constitutively active MKK1/2 (MKK1/2-CA) increased TP protein levels and cell viability in curcumin- and MMC-co-treated cells. In contrast, U0126, a MKK1/2 inhibitor, augmented the cytotoxic effect and the down-regulation of TP by curcumin and MMC. Specific inhibition of TP by siRNA significantly enhanced MMC-induced cell death and cell growth inhibition. Our results suggest that suppression of TP expression or administration of curcumin along with MMC may be a novel lung cancer therapeutic modality in the future. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

Reduced prevalence of chronic tubal inflammation in tubal pregnancies after levonorgestrel emergency contraception failure.

PubMed

Li, Cheng; Meng, Chun-Xia; Sun, Lu-Lu; Zhao, Wei-Hong; Zhang, Mei; Zhang, Jian; Cheng, Linan

2015-05-01

The aim of this study was to compare chronic fallopian tubal inflammatory disease and fibrosis between patients with general tubal pregnancy (TP) and TP with levonorgestrel (LNG) emergency contraception (EC) failure. We retrospectively studied patients with general TP (n = 79) and TP following LNG-EC failure (n = 81) within the same conception cycle. Information on the gynecological features of each subject was collected. Pelvic inflammatory disease and associated sequelae were assessed by the serum Chlamydia trachomatis (CT) IgG test, laparoscopic evaluation of tubal damage, and histopathological observation of tube tissues. Chi-square and Student's t-tests were employed to determine the difference between the two groups. Compared with general TP, cases of TP following LNG-EC failure subjects were less likely to have a history of previous ectopic pregnancy (5.06% vs. 18.52%, p = 0.009) and adnexal surgery (6.33% vs. 22.22%, p = 0.010). Patients with TP following LNG-EC failure were less likely to have pelvic inflammatory disease and associated sequelae than those with general TP, as revealed by positive reaction to anti-CT IgG (18.18% vs. 35.94%, p = 0.031), assessment of tubal damage (grade I: 5.06% vs. 17.28%; grade II: 2.53% vs. 11.11%; grade III: 1.27% vs. 6.17%; p = 0.001), infiltration of chronic inflammatory cells (10.91% vs. 62.50%, p < 0.001), and positive Masson's staining (7.69% vs. 39.58%; p < 0.001). Compared with cases of general TP, cases of TP following LNG-EC failure exhibited reduced rates of CT infection, fallopian tubal inflammation, and/or fibrosis. Copyright © 2015 John Wiley & Sons, Ltd.

Unusual stoichiometry control in the atomic layer deposition of manganese borate films from manganese bis(tris(pyrazolyl)borate) and ozone

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

Klesko, Joseph P.; Bellow, James A.; Saly, Mark J.

The atomic layer deposition (ALD) of films with the approximate compositions Mn{sub 3}(BO{sub 3}){sub 2} and CoB{sub 2}O{sub 4} is described using MnTp{sub 2} or CoTp{sub 2} [Tp = tris(pyrazolyl)borate] with ozone. The solid state decomposition temperatures of MnTp{sub 2} and CoTp{sub 2} are ∼370 and ∼340 °C, respectively. Preparative-scale sublimations of MnTp{sub 2} and CoTp{sub 2} at 210 °C/0.05 Torr afforded >99% recoveries with <0.1% nonvolatile residues. Self-limited ALD growth was demonstrated at 325 °C for MnTp{sub 2} or CoTp{sub 2} with ozone as the coreactant. The growth rate for the manganese borate process was 0.19 Å/cycle within the ALD window of 300–350 °C. The growth ratemore » for the cobalt borate process was 0.39–0.42 Å/cycle at 325 °C. X-ray diffraction of the as-deposited films indicated that they were amorphous. Atomic force microscopy of 35–36 nm thick manganese borate films grown within the 300–350 °C ALD window showed root mean square surface roughnesses of 0.4–0.6 nm. Film stoichiometries were assessed by x-ray photoelectron spectroscopy and time of flight-elastic recoil detection analysis. The differing film stoichiometries obtained from the very similar precursors MnTp{sub 2} and CoTp{sub 2} are proposed to arise from the oxidizing ability of the intermediate high valent manganese oxide layers and lack thereof for cobalt.« less

Teriparatide and the treatment of bisphosphonate-related osteonecrosis of the jaw: a rat model.

PubMed

Ersan, N; van Ruijven, L J; Bronckers, A L J J; Olgaç, V; Ilgüy, D; Everts, V

2014-01-01

The objectives of this study were to establish a bisphosphonate-related osteonecrosis of the jaw (BRONJ) rat model and to analyse the effects of teriparatide (TP) on this model. Sprague-Dawley rats were divided into three groups: I-zoledronic acid (ZA, n = 10); II-ZA and teriparatide (ZA + TP, n = 10); III-control (n = 10). Osteonecrosis was induced by administering zoledronic acid to groups ZA and ZA + TP. A week after the injections, rats underwent extraction of the first left mandibular molar. Following a four week period, TP was administered to the ZA + TP group for 28 days. Upon killing, extraction sockets were examined clinically, radiologically and histopathologically. Clinical examination revealed necrotic bone exposure in none of the animals. MicroCT (µCT) examination showed that bone mineral density of the newly formed bone in the extraction socket was lower in the ZA group than in the ZA + TP group (p < 0.05). Histopathological examination revealed that only the ZA and ZA + TP groups developed osteonecrosis, and the osteonecrotic bone area in the ZA group was larger than that in the ZA + TP group (p < 0.05). Tartrate-resistant acid phosphatase (TRAcP) enzyme histochemistry revealed that the number of detached and large osteoclasts were higher in the ZA group than in other groups, whereas the number of apoptotic osteoclasts in both ZA and ZA + TP groups were higher than in the control group (p < 0.05). Our data indicate that bisphosphonate-related osteonecrosis of the jaw model used in the present study is an attractive model to investigate treatment modalities and that TP might be an effective treatment in BRONJ.

Browning of subcutaneous fat and higher surface temperature in response to phenotype selection for advanced endurance exercise performance in male DUhTP mice.

PubMed

Brenmoehl, J; Ohde, D; Albrecht, E; Walz, C; Tuchscherer, A; Hoeflich, A

2017-02-01

For the assessment of genetic or conditional factors of fat cell browning, novel and polygenic animal models are required. Therefore, the long-term selected polygenic mouse line DUhTP originally established in Dummerstorf for high treadmill performance is used. DUhTP mice are characterized by increased fat accumulation in the sedentary condition and elevated fat mobilization during mild voluntary physical activity. In the present study, the phenotype of fat cell browning of subcutaneous fat and a potential effect on oral glucose tolerance, an indicator of metabolic health, were addressed in DUhTP mice. Analysis of peripheral fat pads revealed increased brite (brown-in-white) subcutaneous adipose tissues and in subcutaneous fat from DUhTP mice higher levels of irisin and different markers of fat cell browning like T-box transcription factor (Tbx1), PPARα, and uncoupling protein (UCP1) (P < 0.05) when compared to unselected controls. UCP1 was further increased in subcutaneous fat from DUhTP mice in response to mild exercise (fourfold, P < 0.05). In addition, surface temperature of DUhTP mice was increased when compared to controls indicating a physiological effect of increased UCP1 expression. The present study suggests that DUhTP mice exhibit different markers of mitochondrial biogenesis and fat browning without external stimuli. At an age of 43 days, sedentary DUhTP mice have improved metabolic health as judged from lower levels of blood glucose after an oral glucose tolerance test. Consequently, the non-inbred mouse model DUhTP represents a novel model for the identification of fat cell browning mechanisms in white adipose tissues.

Expected orbit determination performance for the TOPEX/Poseidon mission

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

Nerem, R.S.; Putney, B.H.; Marshall, J.A.

1993-03-01

The TOPEX/Poseidon (T/P) mission, launched during the summer of 1992, has the requirement that the radial component of its orbit must be computed to an accuracy of 13 cm root-mean-square (rms) or better, allowing measurements of the sea surface height to be computed to similar accuracy when the satellite height is differenced with the altimeter measurements. This will be done by combining precise satellite tracking measurements with precise models of the forces acting on the satellite. The Space Geodesy Branch at Goddard Space Flight Center (GSFC), as part of the T/P precision orbit determination (POD) Team, has the responsibility withinmore » NASA for the T/P precise orbit computations. The prelaunch activities of the T/P POD Team have been mainly directed towards developing improved models of the static and time-varying gravitational forces acting on T/P and precise models for the non-conservative forces perturbing the orbit of T/P such as atmospheric drag, solar and Earth radiation pressure, and thermal imbalances. The radial orbit error budget for T/P allows 10 cm rms error due to gravity field mismodeling, 3 cm due to solid Earth and ocean tides, 6 cm due to radiative forces, and 3 cm due to atmospheric drag. A prelaunch assessment of the current modeling accuracies for these forces indicates that the radial orbit error requirements can be achieved with the current models, and can probably be surpassed once T/P tracking data are used to fine tune the models. Provided that the performance of the T/P spacecraft is nominal, the precise orbits computed by the T/P POD Team should be accurate to 13 cm or better radially.« less

Mitochondrial phylogeny, divergence history and high-altitude adaptation of grassland caterpillars (Lepidoptera: Lymantriinae: Gynaephora) inhabiting the Tibetan Plateau.

PubMed

Yuan, Ming-Long; Zhang, Qi-Lin; Zhang, Li; Jia, Cheng-Lin; Li, Xiao-Peng; Yang, Xing-Zhuo; Feng, Run-Qiu

2018-05-01

Grassland caterpillars (Lepidoptera: Lymantriinae: Gynaephora) are the most important pests in alpine meadows of the Tibetan Plateau (TP) and have well adapted to high-altitude environments. To further understand the evolutionary history and their adaptation to the TP, we newly determined seven complete TP Gynaephora mitogenomes. Compared to single genes, whole mitogenomes provided the best phylogenetic signals and obtained robust results, supporting the monophyly of the TP Gynaephora species and a phylogeny of Arctiinae + (Aganainae + Lymantriinae). Incongruent phylogenetic signals were found among single mitochondrial genes, none of which recovered the same phylogeny as the whole mitogenome. We identified six best-performing single genes using Shimodaira-Hasegawa tests and found that the combinations of rrnS and either cox1 or cox3 generated the same phylogeny as the whole mitogenome, indicating the phylogenetic potential of these three genes for future evolutionary studies of Gynaephora. The TP Gynaephora species were estimated to radiate on the TP during the Pliocene and Quaternary, supporting an association of the diversification and speciation of the TP Gynaephora species with the TP uplifts and associated climate changes during this time. Selection analyses revealed accelerated evolutionary rates of the mitochondrial protein-coding genes in the TP Gynaephora species, suggesting that they accumulated more nonsynonymous substitutions that may benefit their adaptation to high altitudes. Furthermore, signals of positive selection were detected in nad5 of two Gynaephora species with the highest altitude-distributions, indicating that this gene may contribute to Gynaephora's adaptation to divergent altitudes. This study adds to the understanding of the TP Gynaephora evolutionary relationships and suggests a link between mitogenome evolution and ecological adaptation to high-altitude environments in grassland caterpillars. Copyright © 2018 Elsevier Inc. All rights reserved.

Activation of Sirt1/FXR Signaling Pathway Attenuates Triptolide-Induced Hepatotoxicity in Rats.

PubMed

Yang, Jing; Sun, Lixin; Wang, Lu; Hassan, Hozeifa M; Wang, Xuan; Hylemon, Phillip B; Wang, Tao; Zhou, Huiping; Zhang, Luyong; Jiang, Zhenzhou

2017-01-01

Triptolide (TP), a diterpenoid isolated from Tripterygium wilfordii Hook F, has an excellent pharmacological profile of immunosuppression and anti-tumor activities, but its clinical applications are severely restricted due to its severe and cumulative toxicities. The farnesoid X receptor (FXR) is the master bile acid nuclear receptor and plays an important role in maintaining hepatic metabolism homeostasis. Hepatic Sirtuin (Sirt1) is a key regulator of the FXR signaling pathway and hepatic metabolism homeostasis. The aims of this study were to determine whether Sirt1/FXR signaling pathway plays a critical role in TP-induced hepatotoxicity. Our study revealed that the intragastric administration of TP (400 μg/kg body weight) for 28 consecutive days increased bile acid accumulation, suppressed hepatic gluconeogenesis in rats. The expression of bile acid transporter BSEP was significantly reduced and cholesterol 7α-hydroxylase (CYP7A1) was markedly increased in the TP-treated group, whereas the genes responsible for hepatic gluconeogenesis were suppressed in the TP-treated group. TP also modulated the FXR and Sirt1 by decreasing its expression both in vitro and in vivo . The Sirt1 agonist SRT1720 and the FXR agonist obeticholic acid (OCA) were used both in vivo and in vitro . The remarkable liver damage induced by TP was attenuated by treatment with either SRT1720 or OCA, as reflected by decreased levels of serum total bile acids and alkaline phosphatase and increased glucose levels. Meanwhile, SRT1720 significantly alleviated TP-induced FXR suppression and FXR-targets involved in hepatic lipid and glucose metabolism. Based on these results, we conclude that Sirt1/FXR inactivation plays a critical role in TP-induced hepatotoxicity. Moreover, Sirt1/FXR axis represents a novel therapeutic target that could potentially ameliorate TP-induced hepatotoxicity.

Effects of tea polyphenols on the post-mortem integrity of large yellow croaker (Pseudosciaena crocea) fillet proteins.

PubMed

Zhao, Jin; Lv, Weijin; Wang, Jinlin; Li, Jianrong; Liu, Xiaoxiang; Zhu, Junli

2013-12-01

Tea polyphenols (TP) are known to be important for the post-mortem deterioration of fish muscle and can enhance food quality. To shed light on the influence of TP on the status of large yellow croaker muscle proteins, control and treated fillets (0.1% TP, 0.2% TP and 0.3% TP, w/v) were analysed periodically for myofibrillar protein functional properties (Ca(2+)-ATPase activity, surface hydrophobicity, total sulfhydryl content, emulsion stability index and rheological behaviour). Degradation of the myofibrillar protein myosin could be clearly observed; several proteins were also observed to vary in abundance following post-mortem storage for 25 days. The present study offers new evidence that TP have an effective impact on muscle protein integrity post-mortem. Copyright © 2013 Elsevier Ltd. All rights reserved.

Using cumulative diet data and stable isotope analysis to determine trophic position of walleye Sander vitreus in a large, complex system

USGS Publications Warehouse

Fincel, Mark J.; James, Daniel A.; Chipps, Steven R.; Davis, Blake A.

2014-01-01

Diet studies have traditionally been used to determine prey use and food web dynamics, while stable isotope analysis provides for a time-integrated approach to evaluate food web dynamics and characterize energy flow in aquatic systems. Direct comparison of the two techniques is rare and difficult to conduct in large, species rich systems. We compared changes in walleye Sander vitreus trophic position (TP) derived from paired diet content and stable isotope analysis. Individual diet-derived TP estimates were dissimilar to stable isotope-derived TP estimates. However, cumulative diet-derived TP estimates integrated from May 2001 to May 2002 corresponded to May 2002 isotope-derived estimates of TP. Average walleye TP estimates from the spring season appear representative of feeding throughout the entire previous year.

A dipole pattern of summertime rainfall across the Indian subcontinent and the Tibetan Plateau

NASA Astrophysics Data System (ADS)

Jiang, X.; Ting, M.

2017-12-01

The Tibetan Plateau (TP) has long been regarded as a key driver for the formation and variations of the Indian summer monsoon (ISM). Recent studies, however, indicated that the ISM also exerts a considerable impact on rainfall variations in the TP, suggesting that the ISM and the TP should be considered as an interactive system. From this perspective, we investigate the co-variability of the July-August mean rainfall across the Indian subcontinent (IS) and the TP. We found that the interannual variation of IS and TP rainfall exhibits a dipole pattern in which rainfall in the central and northern IS tends to be out of phase with that in the southeastern TP. This dipole pattern is associated with significant anomalies in rainfall, atmospheric circulation, and water vapor transport over the Asian continent and nearby oceans. Rainfall anomalies and the associated latent heating in the central and northern IS tend to induce changes in regional circulation -that suppress rainfall in the southeastern TP and vice versa. Furthermore, the sea surface temperature anomalies in the tropical southeastern Indian Ocean can trigger the dipole rainfall pattern by suppressing convection over the central IS and the northern Bay of Bengal, which further induces anomalous anticyclonic circulation to the south of TP that favors more rainfall in the southeastern TP by transporting more water vapor to the region. The dipole pattern is also linked to the Silk-Road wave train due to its link to rainfall over the northwestern IS.

Structural, Bioinformatic, and In Vivo Analyses of Two Treponema pallidum Lipoproteins Reveal a Unique TRAP Transporter

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

Deka, Ranjit K.; Brautigam, Chad A.; Goldberg, Martin

2012-05-25

Treponema pallidum, the bacterial agent of syphilis, is predicted to encode one tripartite ATP-independent periplasmic transporter (TRAP-T). TRAP-Ts typically employ a periplasmic substrate-binding protein (SBP) to deliver the cognate ligand to the transmembrane symporter. Herein, we demonstrate that the genes encoding the putative TRAP-T components from T. pallidum, tp0957 (the SBP), and tp0958 (the symporter), are in an operon with an uncharacterized third gene, tp0956. We determined the crystal structure of recombinant Tp0956; the protein is trimeric and perforated by a pore. Part of Tp0956 forms an assembly similar to those of 'tetratricopeptide repeat' (TPR) motifs. The crystal structure ofmore » recombinant Tp0957 was also determined; like the SBPs of other TRAP-Ts, there are two lobes separated by a cleft. In these other SBPs, the cleft binds a negatively charged ligand. However, the cleft of Tp0957 has a strikingly hydrophobic chemical composition, indicating that its ligand may be substantially different and likely hydrophobic. Analytical ultracentrifugation of the recombinant versions of Tp0956 and Tp0957 established that these proteins associate avidly. This unprecedented interaction was confirmed for the native molecules using in vivo cross-linking experiments. Finally, bioinformatic analyses suggested that this transporter exemplifies a new subfamily of TPATs (TPR-protein-associated TRAP-Ts) that require the action of a TPR-containing accessory protein for the periplasmic transport of a potentially hydrophobic ligand(s).« less

Phosphatidylcholine Transfer Protein Interacts with Thioesterase Superfamily Member 2 to Attenuate Insulin Signaling

PubMed Central

Ersoy, Baran A.; Tarun, Akansha; D’Aquino, Katharine; Hancer, Nancy J.; Ukomadu, Chinweike; White, Morris F.; Michel, Thomas; Manning, Brendan D.; Cohen, David E.

2014-01-01

Phosphatidylcholine transfer protein (PC-TP) is a phospholipid-binding protein that is enriched in liver and that interacts with thioesterase superfamily member 2 (THEM2). Mice lacking either protein exhibit improved hepatic glucose homeostasis and are resistant to diet-induced diabetes. Insulin receptor substrate 2 (IRS2) and mammalian target of rapamycin complex 1 (mTORC1) are key effectors of insulin signaling, which is attenuated in diabetes. We found that PC-TP inhibited IRS2, as evidenced by insulin-independent IRS2 activation following knockdown, genetic ablation, or chemical inhibition of PC-TP. In addition, IRS2 was activated after knockdown of THEM2, providing support for a role for the interaction of PC-TP with THEM2 in suppressing insulin signaling. Additionally, we showed that PC-TP bound to tuberous sclerosis complex 2 (TSC2) and stabilized the components of the TSC1-TSC2 complex, which functions to inhibit mTORC1. Preventing phosphatidylcholine from binding to PC-TP disrupted interactions of PC-TP with THEM2 and TSC2, and disruption of the PC-TP–THEM2 complex was associated with increased activation of both IRS2 and mTORC1. In livers of mice with genetic ablation of PC-TP or that had been treated with a PC-TP inhibitor, steady-state amounts of IRS2 were increased, whereas those of TSC2 were decreased. These findings reveal a phospholipid-dependent mechanism that suppresses insulin signaling downstream of its receptor. PMID:23901139

Impacts of northern Tibetan Plateau on East Asian summer rainfall via modulating midlatitude transient eddies

NASA Astrophysics Data System (ADS)

Deng, Jiechun; Xu, Haiming; Shi, Ning; Zhang, Leying; Ma, Jing

2017-08-01

Roles of the Tibetan Plateau (TP) in forming and changing the seasonal Asian climate system have been widely explored. However, little is known about modulation effects of the TP on extratropical transient eddies (TEs) and subsequent synoptic responses of the East Asian rainfall. In this study, the Community Atmosphere Model version 5.1 coupled with a slab ocean model is employed to highlight the important role of the TP in regulating the upper-tropospheric transient wave train. Comparison between sensitivity experiments with and without the TP shows that the northern TP excites a strong anomalous anticyclone, which shifts the upper-level East Asian westerly jet northward and helps transfer barotropic and baroclinic energy from the mean flow to the synoptic TE flow. The transient wave train is primarily shifted northward by northern TP and is forced to propagate southeastward along the eastern flank of the TP until reaching eastern China. Before the strengthening of monsoonal southerlies, the TP-modulated transient wave train cools the troposphere, which decreases the static stability over northern China. Meanwhile, the associated anomalous warm advection induces ascending motion, leading to excessive rainfall by releasing unstable energy as the southerly strengthens. Due to the southeastward propagation of the wave train, anomalous heavy rainfall subsequently appears over eastern China from north to south, which increases day-to-day rainfall variation in this region. Additionally, occurrence of this upper-tropospheric transient wave train associated with low-level southerly peak is substantially increased by northern TP.

Analytical and clinical comparison of Elecsys syphilis (Roche®) - Architect syphilis TP and reformulated Architect syphilis TP (Abbott®) assay.

PubMed

De Keukeleire, Steven; Desmet, Stefanie; Lagrou, Katrien; Oosterlynck, Julie; Verhulst, Manon; Van Besien, Jessica; Saegeman, Veroniek; Reynders, Marijke

2017-03-01

The performance of Elecsys Syphilis was compared to Architect Syphilis TP and Reformulated Architect Syphilis TP. The overall sensitivity and specificity were 98.4% and 99.5%, 97.7% and 97.1%, and 99.2% and 99.7% respectively. The assays are comparable and considered adequate for syphilis screening. Copyright © 2016 Elsevier Inc. All rights reserved.

[Comparison among three translucency parameters].

PubMed

Fang, Xiong; Hui, Xia

2017-06-01

This study aims to compare the three commonly used translucency parameters in prosthodontics: transmittance (T), contrast ratio (CR), and translucency parameter (TP). Six platelet specimens were composed of Vita enamel and dental porcelain. The initial thickness was 1.2 mm. The specimens were gradually ground to 1.0, 0.8, 0.6, 0.4, and 0.2 mm. T, color parameters, and reflection were measured by a spectrocolorimeter for each corresponding thickness. T, CR and TP were calculated and compared. TP increased, whereas CR decreased, with decreasing thickness. Moreover, 
T increased with decreasing thickness, and exponential relationships were found. Two-way ANOVA showed statistical significance between T and thickness, except between T and the 1.2 mm and 1.0 mm enamel porcelain groups. No difference was found among the coefficient variations (CV) of T, CR and TP. Curve fitting indicated the existence of exponential relationships between T and CR and between T and TP. The values for goodness of fit with statistical significance were 0.951 and 0.939, respectively (P<0.05). Under the experimental conditions, T, TP and CR achieved the same CV. T and TP, as well as T and CR, were found with exponential relationships. The value of CR and TP could not represent the translucency precisely, especially when comparing the changing ratios.

Evidence of maternal effects on temperature preference in side-blotched lizards: implications for evolutionary response to climate change

PubMed Central

Paranjpe, Dhanashree A; Bastiaans, Elizabeth; Patten, Amy; Cooper, Robert D; Sinervo, Barry

2013-01-01

Natural populations respond to selection pressures like increasing local temperatures in many ways, including plasticity and adaptation. To predict the response of ectotherms like lizards to local temperature increase, it is essential to estimate phenotypic variation in and determine the heritability of temperature-related traits like average field body temperature (Tb) and preferred temperature (Tp). We measured Tp of Uta stansburiana in a laboratory thermal gradient and assessed the contribution of sex, reproductive status and throat color genotype to phenotypic variation in Tb of adult lizards. Females had higher Tp than males. However, they temporarily preferred lower temperature when gravid than when nongravid. Using a nested half-sib design for genetic crosses in the laboratory, we estimated relative contributions of additive genetic variation and maternal effects to Tp of hatchlings. Our results show that maternal effects, but not additive genetic variation, influence Tp of hatchlings in U. stansburiana. Maternal Tp and the presence or absence of blue throat color alleles significantly influenced Tp of hatchlings. We discuss ecological and evolutionary consequences of these maternal effects in the context of rapid climate change and natural selection that we measure on progeny survival to maturity as a function of maternal Tp. PMID:23919144

The Structure of the Metal Transporter Tp34 and its Affinity for Divalent Metal Ions

NASA Astrophysics Data System (ADS)

Knutsen, Gregory; Deka, Ranjit; Brautigam, Chad; Tomchick, Diana; Machius, Mischa; Norgard, Michael

2007-10-01

Tp34 is periplasmic membrane protein of the nonculitvatable spirochete Treponema pallidum, the pathogen of syphillis. It was proposed that Tp34 is a divalent metal transporter, but the identity of the preferred metal ion(s) was unclear. In this study we investigated the ability of divalent metal ions to induce rTp34 dimerization using hydrodynamic techniques and determine the crystal structure of metal bound forms. Using analytical ultracentrifugation sedimentation velocity experiments, we determined that cobalt is superior to nickel at inducing the dimerization of rTp34. rTp34 was crystallized and selected crystals were incubated at a pH 7.5 with CuSO4 and NiSO4. Diffraction experiments were conducted and the processed electron density maps showed that copper was bound to the major metal binding site as well as to three additional minor binding sites. By contrast nickel was only bound to the major metal binding site in one monomer and to three additional minor sites. These results along with previous findings support evidence of Tp34 being involved with metal transport and/or iron utilization.

Future vegetation ecosystem response to warming climate over the Tibetan Plateau

NASA Astrophysics Data System (ADS)

Bao, Y.; Gao, Y.; Wang, Y.

2017-12-01

The amplified vegetation response to climate variability has been found over the Tibetan Plateau (TP) in recent decades. In this study, the potential impacts of 21st century climate change on the vegetation ecosystem over the TP are assessed based on the dynamic vegetation outputs of models from Coupled Model Intercomparison Project Phase 5 (CMIP5), and the sensitivity of the TP vegetation in response to warming climate was investigated. Models project a continuous and accelerating greening in future, especially in the eastern TP, which closely associates with the plant type upgrade due to the pronouncing warming in growing season.Vegetation leaf area index (LAI) increase well follows the global warming, suggesting the warming climate instead of co2 fertilization controlls the future TP plant growth. The warming spring may advance the start of green-up day and extend the growing season length. More carbon accumulation in vegetation and soil will intensify the TP carbon cycle and will keep it as a carbon sink in future. Keywords: Leaf Area Index (LAI), Climate Change, Global Dynamic Vegetation Models (DGVMs), CMIP5, Tibetan Plateau (TP)

Characterisation of single domain ATP-binding cassette protien homologues of Theileria parva.

PubMed

Kibe, M K; Macklin, M; Gobright, E; Bishop, R; Urakawa, T; ole-MoiYoi, O K

2001-09-01

Two distinct genes encoding single domain, ATP-binding cassette transport protein homologues of Theileria parva were cloned and sequenced. Neither of the genes is tandemly duplicated. One gene, TpABC1, encodes a predicted protein of 593 amino acids with an N-terminal hydrophobic domain containing six potential membrane-spanning segments. A single discontinuous ATP-binding element was located in the C-terminal region of TpABC1. The second gene, TpABC2, also contains a single C-terminal ATP-binding motif. Copies of TpABC2 were present at four loci in the T. parva genome on three different chromosomes. TpABC1 exhibited allelic polymorphism between stocks of the parasite. Comparison of cDNA and genomic sequences revealed that TpABC1 contained seven short introns, between 29 and 84 bp in length. The full-length TpABC1 protein was expressed in insect cells using the baculovirus system. Application of antibodies raised against the recombinant antigen to western blots of T. parva piroplasm lysates detected an 85 kDa protein in this life-cycle stage.

TP53 supports basal-like differentiation of mammary epithelial cells by preventing translocation of deltaNp63 into nucleoli

NASA Astrophysics Data System (ADS)

Munne, Pauliina M.; Gu, Yuexi; Tumiati, Manuela; Gao, Ping; Koopal, Sonja; Uusivirta, Sanna; Sawicki, Janet; Wei, Gong-Hong; Kuznetsov, Sergey G.

2014-04-01

Multiple observations suggest a cell type-specific role for TP53 in mammary epithelia. We developed an in vitro assay, in which primary mouse mammary epithelial cells (mMECs) progressed from lumenal to basal-like phenotypes based on expression of Krt18 or ΔNp63, respectively. Such transition was markedly delayed in Trp53-/- mMECs suggesting that Trp53 is required for specification of the basal, but not lumenal cells. Evidence from human basal-like cell lines suggests that TP53 may support the activity of ΔNp63 by preventing its translocation from nucleoplasm into nucleoli. In human lumenal cells, activation of TP53 by inhibiting MDM2 or BRCA1 restored the nucleoplasmic expression of ΔNp63. Trp53-/- mMECs eventually lost epithelial features resulting in upregulation of MDM2 and translocation of ΔNp63 into nucleoli. We propose that TP63 may contribute to TP53-mediated oncogenic transformation of epithelial cells and shed light on tissue- and cell type-specific biases observed for TP53-related cancers.

TP53 supports basal-like differentiation of mammary epithelial cells by preventing translocation of deltaNp63 into nucleoli.

PubMed

Munne, Pauliina M; Gu, Yuexi; Tumiati, Manuela; Gao, Ping; Koopal, Sonja; Uusivirta, Sanna; Sawicki, Janet; Wei, Gong-Hong; Kuznetsov, Sergey G

2014-04-11

Multiple observations suggest a cell type-specific role for TP53 in mammary epithelia. We developed an in vitro assay, in which primary mouse mammary epithelial cells (mMECs) progressed from lumenal to basal-like phenotypes based on expression of Krt18 or ΔNp63, respectively. Such transition was markedly delayed in Trp53(-/-) mMECs suggesting that Trp53 is required for specification of the basal, but not lumenal cells. Evidence from human basal-like cell lines suggests that TP53 may support the activity of ΔNp63 by preventing its translocation from nucleoplasm into nucleoli. In human lumenal cells, activation of TP53 by inhibiting MDM2 or BRCA1 restored the nucleoplasmic expression of ΔNp63. Trp53(-/-) mMECs eventually lost epithelial features resulting in upregulation of MDM2 and translocation of ΔNp63 into nucleoli. We propose that TP63 may contribute to TP53-mediated oncogenic transformation of epithelial cells and shed light on tissue- and cell type-specific biases observed for TP53-related cancers.

The northward shift of the Tibetan Plateau as an important factor for understanding East Asian climate during Cenozoic

NASA Astrophysics Data System (ADS)

Zhang, Ran; Jiang, Dabang; Ramstein, Gilles; Zhang, Zhongshi; Lippert, Peter C.; Yu, Entao

2017-04-01

Previous climate modeling studies suggest that the surface uplift of the Himalaya-Tibetan plateau (TP) is a crucial parameter for the onset and enhancement of the East Asian monsoon during the Cenozoic. However, most of these studies have only considered the Himalaya-TP in its present location despite numerous geophysical studies that reconstruct the Himalaya-TP 10° or more of latitude to the south during the early Paleogene. We have designed a series of climate simulations that account for not only changes in the surface elevation of the Himalaya-TP, but also the latitudinal distribution of this regionally high elevation. Here we demonstrate that the East Asian climate strongly depends on the latitude of the Himalaya-TP. The northward motion of the Himalaya-TP likely contribute to the reorganization atmospheric circulation in East Asia, thereby leading to intensified inland Asian aridity and enhanced monsoon climate over East Asia. Moreover, our simulations also bring new constrains on the southern margin of a modern-elevation proto-Himalaya-TP in the Eocene.

α-Terpineol reduces cancer pain via modulation of oxidative stress and inhibition of iNOS.

PubMed

Gouveia, Daniele Nascimento; Costa, Janara Santos; Oliveira, Marlange Almeida; Rabelo, Thallita Kelly; Silva, Ana Mara de Oliveira E; Carvalho, Adriana Andrade; Miguel-Dos-Santos, Rodrigo; Lauton-Santos, Sandra; Scotti, Luciana; Scotti, Marcus Tullius; Santos, Márcio Roberto Viana Dos; Quintans-Júnior, Lucindo José; Albuquerque Junior, Ricardo Luiz Cavalcanti De; Guimarães, Adriana Gibara

2018-06-11

α-Terpineol (TP) is present in a wide range of essential oils of the genus Eucalyptus, with recognized potential for a range of biological effects, such as analgesic. Hence, our study aimed to investigate the effect of TP on cancer pain induced by sarcoma 180 in Swiss mice. Our results showed that TP reduced significantly mechanical hyperalgesia and spontaneous and palpation-induced nociception, improved paw use without reducing tumor growth and grip strength. Importantly, no evident biochemical and hematological toxicity was oberved. Furthermore, TP increased the tissue antioxidant capacity due to ferric-reducing antioxidant power (FRAP) and glutathione (GSH). TP also reduced inducible nitric oxide synthase (iNOS) immunocontent in the tumors. Molecular docking estimated that TP binds within the same range of iNOS regions (other iNOS inhibitors), such as N-Nitroarginine methyl ester (L-NAME). These data provide strong evidence that TP may be an interesting candidate for the development of new safe analgesic drugs that are effective for cancer pain control. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Antimicrobial effect and membrane-active mechanism of tea polyphenols against Serratia marcescens.

PubMed

Yi, Shumin; Wang, Wei; Bai, Fengling; Zhu, Junli; Li, Jianrong; Li, Xuepeng; Xu, Yongxia; Sun, Tong; He, Yutang

2014-02-01

In this study, we investigated the antimicrobial effect of tea polyphenols (TP) against Serratia marcescens and examined the related mechanism. Morphology changes of S. marcescens were first observed by transmission electron microscopy after treatment with TP, which indicated that the primary inhibition action of TP was to damage the bacterial cell membranes. The permeability of the outer and inner membrane of S. marcescens dramatically increased after TP treatment, which caused severe disruption of cell membrane, followed by the release of small cellular molecules. Furthermore, a proteomics approach based on two-dimensional gel electrophoresis and MALDI-TOF/TOF MS analysis was used to study the difference of membrane protein expression in the control and TP treatment S. marcescens. The results showed that the expression of some metabolism enzymes and chaperones in TP-treated S. marcescens significantly increased compared to the untreated group, which might result in the metabolic disorder of this bacteria. Taken together, our results first demonstrated that TP had a significant growth inhibition effect on S. marcescens through cell membrane damage.

Facile green synthesis of functional nanoscale zero-valent iron and studies of its activity toward ultrasound-enhanced decolorization of cationic dyes.

PubMed

Wang, Xiangyu; Wang, Anqi; Ma, Jun; Fu, Minglai

2017-01-01

For the first time, an integrated green technology by coupling functional nanoscale zero-valent iron (NZVI) with ultrasound (US) was innovatively developed for the enhanced decolorization of malachite green (MG) and methylene blue (MB). The functional NZVI (TP-Fe) was successfully fabricated via a facile, one-step and environmentally-benign approach by directly introducing high pure tea polyphenol (TP), where TP contenting abundant epicatechin was employed as reductant, dispersant and capping agent. Note that neither additional extraction procedure nor protection gas was needed during the entire synthesis process. Affecting factors (including US frequency, initial pH, dye concentration, and reaction temperature) were investigated. Results show that TP-Fe exhibited enhanced activity, antioxidizability and stability over the reaction course, which could be attributed to the functionalization of TP on NZVI and the invigorating effect of US (i.e., improving the mass transfer rate, breaking up the aggregates of TP-Fe nanoparticles, and maintaining the TP-Fe surface activity). The kinetics for MG and MB decolorization by the TP-Fe/US system could be well described by a two-parameter pseudo-first-order decay model, and the activation energies of MG and MB decolorization in this new system were determined to be 21 kJ mol -1 and 24 kJ mol -1 , respectively. In addition, according to the identified reaction products, a possible mechanism associated with MG and MB decolorization with the TP-Fe/US system was proposed. Copyright © 2016 Elsevier Ltd. All rights reserved.

7-Deazapurine containing DNA: efficiency of c7GdTP, c7AdTP and c7IdTP incorporation during PCR-amplification and protection from endodeoxyribonuclease hydrolysis.

PubMed Central

Seela, F; Röling, A

1992-01-01

The enzymatic synthesis of 7-deazapurine nucleoside containing DNA (501 bp) is performed by PCR-amplification (Taq polymerase) using a pUC18 plasmid DNA as template and the triphosphates of 7-deaza-2'-deoxyguanosine (c7Gd), -adenosine (c7Ad) and -inosine (c7Id). c7GdTP can fully replace dGTP resulting in a completely modified DNA-fragment of defined size and sequence. The other two 7-deazapurine triphosphates (c7AdTP) and (c7IdTP) require the presence of the parent purine 2'-deoxyribonucleotides. In purine/7-deazapurine nucleotide mixtures Taq polymerase prefers purine over 7-deazapurine nucleotides but accepts c7GdTP much better than c7AdTP or c7IdTP. As incorporation of 7-deazapurine nucleotides represents a modification of the major groove of DNA it can be used to probe DNA/protein interaction. Regioselective phosphodiester hydrolysis of the modified DNA-fragments was studied with 28 endodeoxyribonucleases. c7Gd is able to protect the DNA from the phosphodiester hydrolysis in more than 20 cases, only a few enzymes (Mae III, Rsa I, Hind III, Pvu II or Taq I) do still hydrolyze the modified DNA. c7Ad protects DNA less efficiently, as this DNA could only be modified in part. The absence of N-7 as potential binding position or a geometric distortion of the recognition duplex caused by the 7-deazapurine base can account for protection of hydrolysis. Images PMID:1738604

Discharge patterns of human tensor palatini motor units during sleep onset.

PubMed

Nicholas, Christian L; Jordan, Amy S; Heckel, Leila; Worsnop, Christopher; Bei, Bei; Saboisky, Julian P; Eckert, Danny J; White, David P; Malhotra, Atul; Trinder, John

2012-05-01

Upper airway muscles such as genioglossus (GG) and tensor palatini (TP) reduce activity at sleep onset. In GG reduced muscle activity is primarily due to inspiratory modulated motor units becoming silent, suggesting reduced respiratory pattern generator (RPG) output. However, unlike GG, TP shows minimal respiratory modulation and presumably has few inspiratory modulated motor units and minimal input from the RPG. Thus, we investigated the mechanism by which TP reduces activity at sleep onset. The activity of TP motor units were studied during relaxed wakefulness and over the transition from wakefulness to sleep. Sleep laboratory. Nine young (21.4 ± 3.4 years) males were studied on a total of 11 nights. Sleep onset. Two TP EMGs (thin, hooked wire electrodes), and sleep and respiratory measures were recorded. One hundred twenty-one sleep onsets were identified (13.4 ± 7.2/subject), resulting in 128 motor units (14.3 ± 13.0/subject); 29% of units were tonic, 43% inspiratory modulated (inspiratory phasic 18%, inspiratory tonic 25%), and 28% expiratory modulated (expiratory phasic 21%, expiratory tonic 7%). There was a reduction in both expiratory and inspiratory modulated units, but not tonic units, at sleep onset. Reduced TP activity was almost entirely due to de-recruitment. TP showed a similar distribution of motor units as other airway muscles. However, a greater proportion of expiratory modulated motor units were active in TP and these expiratory units, along with inspiratory units, tended to become silent over sleep onset. The data suggest that both expiratory and inspiratory drive components from the RPG are reduced at sleep onset in TP.

Consecutive pharmacological activation of PKA and PKC mimics the potent cardioprotection of temperature preconditioning

PubMed Central

Khaliulin, Igor; Parker, Joanna E.; Halestrap, Andrew P.

2010-01-01

Aims Temperature preconditioning (TP) provides very powerful protection against ischaemia/reperfusion. Understanding the signalling pathways involved may enable the development of effective pharmacological cardioprotection. We investigated the interrelationship between activation of protein kinase A (PKA) and protein kinase C (PKC) in the signalling mechanisms of TP and developed a potent pharmacological intervention based on this mechanism. Methods and results Isolated rat hearts were subjected to TP, 30 min global ischaemia, and 60 min reperfusion. Other control and TP hearts were perfused with either sotalol (β-adrenergic blocker) or H-89 (PKA inhibitor). Some hearts were pre-treated with either isoproterenol (β-adrenergic agonist) or adenosine (PKC activator) that were given alone, simultaneously, or sequentially. Pre-treatment with isoproterenol, adenosine, and the consecutive isoproterenol/adenosine treatment was also combined with the PKC inhibitor chelerythrine. Cardioprotection was evaluated by haemodynamic function recovery, lactate dehydrogenase release, measurement of mitochondrial permeability transition pore opening, and protein carbonylation during reperfusion. Cyclic AMP and PKA activity were increased in TP hearts. H-89 and sotalol blocked the cardioprotective effect of TP and TP-induced PKC activation. Isoproterenol, adenosine, and the consecutive treatment increased PKC activity during pre-ischaemia. Isoproterenol significantly reduced myocardial glycogen content. Isoproterenol and adenosine, alone or simultaneously, protected hearts but the consecutive treatment gave the highest protection. Cardioprotective effects of adenosine were completely blocked by chelerythrine but those of the consecutive treatment only attenuated. Conclusion The signal transduction pathway of TP involves PKA activation that precedes PKC activation. Pharmacologically induced consecutive PKA/PKC activation mimics TP and induces extremely potent cardioprotection. PMID:20558443

Modelling of the estimated contributions of different sub-watersheds and sources to phosphorous export and loading from the Dongting Lake watershed, China.

PubMed

Hou, Ying; Chen, Weiping; Liao, Yuehua; Luo, Yueping

2017-11-03

Considerable growth in the economy and population of the Dongting Lake watershed in Southern China has increased phosphorus loading to the lake and resulted in a growing risk of lake eutrophication. This study aimed to reveal the spatial pattern and sources of phosphorus export and loading from the watershed. We applied an export coefficient model and the Dillon-Rigler model to quantify contributions of different sub-watersheds and sources to the total phosphorus (TP) export and loading in 2010. Together, the upper and lower reaches of the Xiang River watershed and the Dongting Lake Area contributed 60.9% of the TP exported from the entire watershed. Livestock husbandry appeared to be the largest anthropogenic source of TP, contributing more than 50% of the TP exported from each secondary sub-watersheds. The actual TP loading to the lake in 2010 was 62.9% more than the permissible annual TP loading for compliance with the Class III water quality standard for lakes. Three primary sub-watersheds-the Dongting Lake Area, the Xiang River, and the Yuan River watersheds-contributed 91.2% of the total TP loading. As the largest contributor among all sources, livestock husbandry contributed nearly 50% of the TP loading from the Dongting Lake Area and more than 60% from each of the other primary sub-watersheds. This study provides a methodology to identify the key sources and locations of TP export and loading in large lake watersheds. The study can provide a reference for the decision-making for controlling P pollution in the Dongting Lake watershed.

Nuclear Countermeasure Activity of TP508 Linked to Restoration of Endothelial Function and Acceleration of DNA Repair

PubMed Central

Olszewska-Pazdrak, Barbara; McVicar, Scott D.; Rayavara, Kempaiah; Moya, Stephanie M.; Kantara, Carla; Gammarano, Chris; Olszewska, Paulina; Fuller, Gerald M.; Sower, Laurie E.; Carney, Darrell H.

2016-01-01

There is increasing evidence that radiation-induced damage to endothelial cells and loss of endothelial function may contribute to both acute radiation syndromes and long-term effects of whole-body nuclear irradiation. Therefore, several drugs are being developed to mitigate the effects of nuclear radiation, most of these drugs will target and protect or regenerate leukocytes and platelets. Our laboratory has demonstrated that TP508, a 23-amino acid thrombin peptide, activates endothelial cells and stem cells to revascularize and regenerate tissues. We now show that TP508 can mitigate radiation-induced damage to endothelial cells in vitro and in vivo. Our in vitro results demonstrate that human endothelial cells irradiation attenuates nitric oxide (NO) signaling, disrupts tube formation and induces DNA double-strand breaks (DSB). TP508 treatment reverses radiation effects on NO signaling, restores tube formation and accelerates the repair of radiation-induced DSB. The radiation-mitigating effects of TP508 on endothelial cells were also seen in CD-1 mice where systemic injection of TP508 stimulated endothelial cell sprouting from aortic explants after 8 Gy irradiation. Systemic doses of TP508 that mitigated radiation-induced endothelial cell damage, also significantly increased survival of CD-1 mice when injected 24 h after 8.5 Gy exposure. These data suggest that increased survival observed with TP508 treatment may be due to its effects on vascular and microvascular endothelial cells. Our study supports the usage of a regenerative drug such as TP508 to activate endothelial cells as a countermeasure for mitigating the effects of nuclear radiation. PMID:27388041

Force decay evaluation of thermoplastic and thermoset elastomeric chains: A mechanical design comparison.

PubMed

Masoud, Ahmed I; Tsay, T Peter; BeGole, Ellen; Bedran-Russo, Ana K

2014-11-01

To compare the following over a period of 8 weeks: (1) force decay between thermoplastic (TP) and thermoset (TS) elastomeric chains; (2) force decay between light (200-g) and heavy (350-g) initial forces; and (3) force decay between direct chains and chain loops (stretched from one pin around the second pin and back to the first pin). TP and TS chains were obtained from American Orthodontics™ (AOTP, AOTS) and ORMCO™ (OrTP, OrTS). Each of the four chain groups was subdivided into four subgroups with 10 specimens per subgroup: (1) direct chains light force, (2) direct chains heavy force, (3) chain loops light force, and (4) chain loops heavy force. The experiment was performed in artificial saliva (pH of 6.75) at 37°C. A significant difference was found between TP and TS chains, with an average mean difference of around 20% more force decay found in the TP chains (P < .001, α  =  .05). There was no significant difference between direct chains and chain loops except in OrTP, in which direct chains showed more force decay. There was also no significant difference in force decay identified when using light vs heavy forces. TS chains decayed less than TP chains, and chain loop retraction was beneficial only when using OrTP chains. Contrary to the interchangeable use of TP and TS chains in the published literature and in clinical practice, this study demonstrates that they perform differently under stress and that a clear distinction should be made between the two.

Constant p53 Pathway Inactivation in a Large Series of Soft Tissue Sarcomas with Complex Genetics

PubMed Central

Pérot, Gaëlle; Chibon, Frédéric; Montero, Audrey; Lagarde, Pauline; de Thé, Hugues; Terrier, Philippe; Guillou, Louis; Ranchère, Dominique; Coindre, Jean-Michel; Aurias, Alain

2010-01-01

Alterations of the p53 pathway are among the most frequent aberrations observed in human cancers. We have performed an exhaustive analysis of TP53, p14, p15, and p16 status in a large series of 143 soft tissue sarcomas, rare tumors accounting for around 1% of all adult cancers, with complex genetics. For this purpose, we performed genomic studies, combining sequencing, copy number assessment, and expression analyses. TP53 mutations and deletions are more frequent in leiomyosarcomas than in undifferentiated pleomorphic sarcomas. Moreover, 50% of leiomyosarcomas present TP53 biallelic inactivation, whereas most undifferentiated pleomorphic sarcomas retain one wild-type TP53 allele (87.2%). The spectrum of mutations between these two groups of sarcomas is different, particularly with a higher rate of complex mutations in undifferentiated pleomorphic sarcomas. Most tumors without TP53 alteration exhibit a deletion of p14 and/or lack of mRNA expression, suggesting that p14 loss could be an alternative genotype for direct TP53 inactivation. Nevertheless, the fact that even in tumors altered for TP53, we could not detect p14 protein suggests that other p14 functions, independent of p53, could be implicated in sarcoma oncogenesis. In addition, both p15 and p16 are frequently codeleted or transcriptionally co-inhibited with p14, essentially in tumors with two wild-type TP53 alleles. Conversely, in TP53-altered tumors, p15 and p16 are well expressed, a feature not incompatible with an oncogenic process. PMID:20884963

Adhesion strength between thermoplastics and its polyurethane coating made by using the technology combination of injection molding and reaction injection molding

NASA Astrophysics Data System (ADS)

Bloß, P.; Böhme, A.; Müller, J.; Krajewsky, P.; Michaelis, J.

2014-05-01

A complete equipment for injection molding (IM) of a thermoplastic (TP) carrier and reaction injection molding (RIM) of polyurethane (PUR) coatings including IM and RIM machines, a color module for PUR, and a robot was built up. A modularly composed sliding split mold was constructed and manufactured allowing different parts including thicker (2 mm thickness) soft touch and thin (0.4 mm) lacquer PUR coatings. As TP PC/ABS and PA6 GF15 compounds were used, and aromatic and aliphatic PUR systems as well. From the parts made by IM+RIM, test specimens for peel force measurements were cut. These investigations were performed prior and after ageing under climatic conditions @ 50 % RH and temperature changes between -30 °C and 90 °C. By varying IM processing parameters, we have found that mold and TP temperatures are particularly important for the adhesion strength between TP and PUR. The waiting time between the end of TP cooling and PUR injection has a minor influence on its mean value. However, to short waiting times may result in inhomogeneous adhesion. It was surprising that surface defects of the TP carrier leads also to inhomogeneous adhesion. We have observed that ageing may cause an increase and decrease of adhesions strength depending on the TP+PUR system used. We have found that the results are valid only for the actual TP and PUR combination. A generalization seems to be inappropriate, hence, the actual combination should be investigated to prevent unwanted surprises when the coated TP part is in its application.

Does Delayed-Time-Point Imaging Improve 18F-FDG-PET in Patients With MALT Lymphoma?: Observations in a Series of 13 Patients.

PubMed

Mayerhoefer, Marius E; Giraudo, Chiara; Senn, Daniela; Hartenbach, Markus; Weber, Michael; Rausch, Ivo; Kiesewetter, Barbara; Herold, Christian J; Hacker, Marcus; Pones, Matthias; Simonitsch-Klupp, Ingrid; Müllauer, Leonhard; Dolak, Werner; Lukas, Julius; Raderer, Markus

2016-02-01

To determine whether in patients with extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue lymphoma (MALT), delayed-time-point 2-F-fluoro-2-deoxy-d-glucose-positron emission tomography (F-FDG-PET) performs better than standard-time-point F-FDG-PET. Patients with untreated histologically verified MALT lymphoma, who were undergoing pretherapeutic F-FDG-PET/computed tomography (CT) and consecutive F-FDG-PET/magnetic resonance imaging (MRI), using a single F-FDG injection, in the course of a larger-scale prospective trial, were included. Region-based sensitivity and specificity, and patient-based sensitivity of the respective F-FDG-PET scans at time points 1 (45-60 minutes after tracer injection, TP1) and 2 (100-150 minutes after tracer injection, TP2), relative to the reference standard, were calculated. Lesion-to-liver and lesion-to-blood SUVmax (maximum standardized uptake values) ratios were also assessed. F-FDG-PET at TP1 was true positive in 15 o f 23 involved regions, and F-FDG-PET at TP2 was true-positive in 20 of 23 involved regions; no false-positive regions were noted. Accordingly, region-based sensitivities and specificities were 65.2% (confidence interval [CI], 45.73%-84.67%) and 100% (CI, 100%-100%) for F-FDG-PET at TP1; and 87.0% (CI, 73.26%-100%) and 100% (CI, 100%-100%) for F-FDG-PET at TP2, respectively. FDG-PET at TP1 detected lymphoma in at least one nodal or extranodal region in 7 of 13 patients, and F-FDG-PET at TP2 in 10 of 13 patients; accordingly, patient-based sensitivity was 53.8% (CI, 26.7%-80.9%) for F-FDG-PET at TP1, and 76.9% (CI, 54.0%-99.8%) for F-FDG-PET at TP2. Lesion-to-liver and lesion-to-blood maximum standardized uptake value ratios were significantly lower at TP1 (ratios, 1.05 ± 0.40 and 1.52 ± 0.62) than at TP2 (ratios, 1.67 ± 0.74 and 2.56 ± 1.10; P = 0.003 and P = 0.001). Delayed-time-point imaging may improve F-FDG-PET in MALT lymphoma.

The Pancreas Is Altered by In Utero Androgen Exposure: Implications for Clinical Conditions Such as Polycystic Ovary Syndrome (PCOS)

PubMed Central

Rae, Mick; Grace, Cathal; Hogg, Kirsten; Wilson, Lisa Marie; McHaffie, Sophie L.; Ramaswamy, Seshadri; MacCallum, Janis; Connolly, Fiona; McNeilly, Alan S.; Duncan, Colin

2013-01-01

Using an ovine model of polycystic ovary syndrome (PCOS), (pregnant ewes injected with testosterone propionate (TP) (100 mg twice weekly) from day (d)62 to d102 of d147 gestation (maternal injection – MI-TP)), we previously reported female offspring with normal glucose tolerance but hyperinsulinemia. We therefore examined insulin signalling and pancreatic morphology in these offspring using quantitative (Q) RT-PCR and western blotting. In addition the fetal pancreatic responses to MI-TP, and androgenic and estrogenic contributions to such responses (direct fetal injection (FI) of TP (20 mg) or diethylstilbestrol (DES) (20 mg) at d62 and d82 gestation) were assessed at d90 gestation. Fetal plasma was assayed for insulin, testosterone and estradiol, pancreatic tissue was cultured, and expression of key β-cell developmental genes was assessed by QRT-PCR. In female d62MI-TP offspring insulin signalling was unaltered but there was a pancreatic phenotype with increased numbers of β-cells (P<0.05). The fetal pancreas expressed androgen receptors in islets and genes involved in β-cell development and function (PDX1, IGF1R, INSR and INS) were up-regulated in female fetuses after d62MI-TP treatment (P<0.05–0.01). In addition the d62MI-TP pancreas showed increased insulin secretion under euglycaemic conditions (P<0.05) in vitro. The same effects were not seen in the male fetal pancreas or when MI-TP was started at d30, before the male programming window. As d62MI-TP increased both fetal plasma testosterone (P<0.05) and estradiol concentrations (P<0.05) we assessed the relative contribution of androgens and estrogens. FI-TP (commencing d62) (not FI-DES treatment) caused elevated basal insulin secretion in vitro and the genes altered by d62MI-TP treatment were similarly altered by FI-TP but not FI-DES. In conclusion, androgen over-exposure alters fetal pancreatic development and β-cell numbers in offspring. These data suggest that that there may be a primary pancreatic phenotype in models of PCOS, and that there may be a distinct male and female pancreas. PMID:23457541

Phosphorus and suspended sediment load estimates for the Lower Boise River, Idaho, 1994-2002

USGS Publications Warehouse

Donato, Mary M.; MacCoy, Dorene E.

2004-01-01

The U.S. Geological Survey used LOADEST, newly developed load estimation software, to develop regression equations and estimate loads of total phosphorus (TP), dissolved orthophosphorus (OP), and suspended sediment (SS) from January 1994 through September 2002 at four sites on the lower Boise River: Boise River below Diversion Dam near Boise, Boise River at Glenwood Bridge at Boise, Boise River near Middleton, and Boise River near Parma. The objective was to help the Idaho Department of Environmental Quality develop and implement total maximum daily loads (TMDLs) by providing spatial and temporal resolution for phosphorus and sediment loads and enabling load estimates made by mass balance calculations to be refined and validated. Regression models for TP and OP generally were well fit on the basis of regression coefficients of determination (R2), but results varied in quality from site to site. The TP and OP results for Glenwood probably were affected by the upstream wastewater-treatment plant outlet, which provides a variable phosphorus input that is unrelated to river discharge. Regression models for SS generally were statistically well fit. Regression models for Middleton for all constituents, although statistically acceptable, were of limited usefulness because sparse and intermittent discharge data at that site caused many gaps in the resulting estimates. Although the models successfully simulated measured loads under predominant flow conditions, errors in TP and SS estimates at Middleton and in TP estimates at Parma were larger during high- and low-flow conditions. This shortcoming might be improved if additional concentration data for a wider range of flow conditions were available for calibrating the model. The average estimated daily TP load ranged from less than 250 pounds per day (lb/d) at Diversion to nearly 2,200 lb/d at Parma. Estimated TP loads at all four sites displayed cyclical variations coinciding with seasonal fluctuations in discharge. Estimated annual loads of TP ranged from less than 8 tons at Diversion to 570 tons at Parma. Annual loads of dissolved OP peaked in 1997 at all sites and were consistently higher at Parma than at the other sites. The ratio of OP to TP varied considerably throughout the year at all sites. Peaks in the OP:TP ratio occurred primarily when flows were at their lowest annual stages; estimated seasonal OP:TP ratios were highest in autumn at all sites. Conversely, when flows were high, the ratio was low, reflecting increased TP associated with particulate matter during high flows. Parma exhibited the highest OP:TP ratio during all seasons, at least 0.60 in spring and nearly 0.90 in autumn. Similar OP:TP ratios were estimated at Glenwood. Whereas the OP:TP ratio for Parma and Glenwood peaked in November or December, decreased from January through May, and increased again after June, estimates for Diversion showed nearly the opposite pattern ? ratios were highest in July and lowest in January and February. This difference might reflect complex biological and geochemical processes involving nutrient cycling in Lucky Peak Lake, but further data are needed to substantiate this hypothesis. Estimated monthly average SS loads were highest at Diversion, about 400 tons per day (ton/d). Average annual loads from 1994 through 2002 were 144,000 tons at Diversion, 33,000 tons at Glenwood, and 88,000 tons at Parma. Estimated SS loads peaked in the spring at all sites, coinciding with high flows. Increases in TP in the reach from Diversion to Glenwood ranged from 200 to 350 lb/d. Decreases in TP were small in this reach only during high flows in January and February 1997. Decreases in SS, were large during high-flow conditions indicating sediment deposition in the reach. Intermittent data at Middleton indicated that increases and decreases in TP in the reach from Glenwood to Middleton were during low- and high-flow conditions, respectively. All constituents increased in the r

Mutations in BHD and TP53 genes, but not in HNF1β gene, in a large series of sporadic chromophobe renal cell carcinoma

PubMed Central

Gad, S; Lefèvre, S H; Khoo, S K; Giraud, S; Vieillefond, A; Vasiliu, V; Ferlicot, S; Molinié, V; Denoux, Y; Thiounn, N; Chrétien, Y; Méjean, A; Zerbib, M; Benoît, G; Hervé, J M; Allègre, G; Bressac-de Paillerets, B; Teh, B T; Richard, S

2006-01-01

BHD, TP53, and HNF1β on chromosome 17 were studied in 92 cases of renal cell carcinoma (46 chromophobe, 19 clear cell, 18 oncocytoma, and nine papillary). Six, thirteen, and zero cases had, respectively BHD, TP53, and HNF1β mutations, (84% mutations involved chromophobe), suggesting a role for BHD and TP53 in chromophobe subtype. PMID:17133269

Comparative proteomic analysis reveals alterations in development and photosynthesis-related proteins in diploid and triploid rice.

PubMed

Wang, Shuzhen; Chen, Wenyue; Yang, Changdeng; Yao, Jian; Xiao, Wenfei; Xin, Ya; Qiu, Jieren; Hu, Weimin; Yao, Haigen; Ying, Wu; Fu, Yaping; Tong, Jianxin; Chen, Zhongzhong; Ruan, Songlin; Ma, Huasheng

2016-09-13

Polyploidy has pivotal influences on rice (Oryza sativa L.) morphology and physiology, and is very important for understanding rice domestication and improving agricultural traits. Diploid (DP) and triploid (TP) rice shows differences in morphological parameters, such as plant height, leaf length, leaf width and the physiological index of chlorophyll content. However, the underlying mechanisms determining these morphological differences are remain to be defined. To better understand the proteomic changes between DP and TP, tandem mass tags (TMT) mass spectrometry (MS)/MS was used to detect the significant changes to protein expression between DP and TP. Results indicated that both photosynthesis and metabolic pathways were highly significantly associated with proteomic alteration between DP and TP based on biological process and pathway enrichment analysis, and 13 higher abundance chloroplast proteins involving in these two pathways were identified in TP. Quantitative real-time PCR analysis demonstrated that 5 of the 13 chloroplast proteins ATPF, PSAA, PSAB, PSBB and RBL in TP were higher abundance compared with those in DP. This study integrates morphology, physiology and proteomic profiling alteration of DP and TP to address their underlying different molecular mechanisms. Our finding revealed that ATPF, PSAA, PSAB, PSBB and RBL can induce considerable expression changes in TP and may affect the development and growth of rice through photosynthesis and metabolic pathways.

Seshat: A Web service for accurate annotation, validation, and analysis of TP53 variants generated by conventional and next-generation sequencing.

PubMed

Tikkanen, Tuomas; Leroy, Bernard; Fournier, Jean Louis; Risques, Rosa Ana; Malcikova, Jitka; Soussi, Thierry

2018-07-01

Accurate annotation of genomic variants in human diseases is essential to allow personalized medicine. Assessment of somatic and germline TP53 alterations has now reached the clinic and is required in several circumstances such as the identification of the most effective cancer therapy for patients with chronic lymphocytic leukemia (CLL). Here, we present Seshat, a Web service for annotating TP53 information derived from sequencing data. A flexible framework allows the use of standard file formats such as Mutation Annotation Format (MAF) or Variant Call Format (VCF), as well as common TXT files. Seshat performs accurate variant annotations using the Human Genome Variation Society (HGVS) nomenclature and the stable TP53 genomic reference provided by the Locus Reference Genomic (LRG). In addition, using the 2017 release of the UMD_TP53 database, Seshat provides multiple statistical information for each TP53 variant including database frequency, functional activity, or pathogenicity. The information is delivered in standardized output tables that minimize errors and facilitate comparison of mutational data across studies. Seshat is a beneficial tool to interpret the ever-growing TP53 sequencing data generated by multiple sequencing platforms and it is freely available via the TP53 Website, http://p53.fr or directly at http://vps338341.ovh.net/. © 2018 Wiley Periodicals, Inc.

The TP53 gene promoter is not methylated in families suggestive of Li-Fraumeni syndrome with no germline TP53 mutations.

PubMed

Finkova, Alena; Vazna, Alzbeta; Hrachovina, Ondrej; Bendova, Sarka; Prochazkova, Kamila; Sedlacek, Zdenek

2009-08-01

Germline TP53 mutations are found in only 70% of families with the Li-Fraumeni syndrome (LFS), and with an even lower frequency in families suggestive of LFS but not meeting clinical criteria of the syndrome. Despite intense efforts, to date, no other genes have been associated with the disorder in a significant number of TP53 mutation-negative families. A search for defects in TP53 other than heterozygous missense mutations showed that neither intron variants nor sequence variants in the TP53 promoter are frequent in LFS, and multiexon deletions have been found to be responsible for LFS only in several cases. Another cancer predisposition syndrome, hereditary non-polyposis colon cancer, has been associated with epigenetic silencing of one allele of the MLH1 or MSH2 genes. This prompted us to test the methylation of the TP53 gene promoter in a set of 14 families suggestive of LFS using bisulphite sequencing of three DNA fragments from the 5' region of the gene. We found no detectable methylation at any of the CG dinucleotides tested. Thus, epigenetic silencing of the TP53 promoter is not a frequent cause of the disorder in families suggestive of LFS but with no germline mutations in the coding part of the gene.

Cone-Beam Computed Tomography as a Diagnostic Method for Determination of Gingival Thickness and Distance between Gingival Margin and Bone Crest

PubMed Central

Borges, Germana Jayme; Ruiz, Luis Fernando Naldi; de Alencar, Ana Helena Gonçalves; Porto, Olavo César Lyra; Estrela, Carlos

2015-01-01

The objective of the present study was to assess cone-beam computed tomography (CBCT) as a diagnostic method for determination of gingival thickness (GT) and distance between gingival margin and vestibular (GMBC-V) and interproximal bone crests (GMBC-I). GT and GMBC-V were measured in 348 teeth and GMBC-I was measured in 377 tooth regions of 29 patients with gummy smile. GT was assessed using transgingival probing (TP), ultrasound (US), and CBCT, whereas GMBC-V and GMBC-I were assessed by transsurgical clinical evaluation (TCE) and CBCT. Statistical analyses used independent t-test, Pearson's correlation coefficient, and simple linear regression. Difference was observed for GT: between TP, CBCT, and US considering all teeth; between TP and CBCT and between TP and US in incisors and canines; between TP and US in premolars and first molars. TP presented the highest means for GT. Positive correlation and linear regression were observed between TP and CBCT, TP and US, and CBCT and US. Difference was observed for GMBC-V and GMBC-I using TCE and CBCT, considering all teeth. Correlation and linear regression results were significant for GMBC-V and GMBC-I in incisors, canines, and premolars. CBCT is an effective diagnostic method to visualize and measure GT, GMBC-V, and GMBC-I. PMID:25918737

Novel Trichoderma polysporum Strain for the Biocontrol of Pseudogymnoascus destructans, the Fungal Etiologic Agent of Bat White Nose Syndrome.

PubMed

Zhang, Tao; Chaturvedi, Vishnu; Chaturvedi, Sudha

2015-01-01

White-nose syndrome (WNS), an emerging disease of hibernating bats, has rapidly spread across eastern North America killing millions of bats. Pseudogymnoascus destructans (Pd), the sole etiologic agent of WNS, is widespread and persistent in bat hibernacula. Control of Pd in the affected sites is urgently needed to break the transmission cycle while minimizing any adverse impact on the native organisms. We isolated a novel strain of Trichoderma polysporum (Tp) from one of the caves at the epicenter of WNS zoonotic. Detailed experimental studies revealed: (1) Tp WPM 39143 was highly adapted to grow at temperatures simulating the cave environment (6°C-15°C), (2) Tp WPM 39143 restricted Pd colony growth in dual culture challenges, (3) Tp WPM 39143 caused four logs reduction of Pd colony forming units and genome copies in autoclaved soil samples from one of the WNS affected caves, (4) Tp WPM 39143 extract showed specific fungicidal activity against Pd in disk diffusion assay, but not against closely related fungus P. pannorum (Pp), (5) Tp WPM 39143 extract retained inhibitory activity after exposure to high temperatures, light and proteinase K, and (6) Inhibitory metabolites in Tp WPM 39143 extract comprised of water-soluble, high polarity compounds. These results suggest that Tp WPM 39143 is a promising candidate for further evaluation as a biocontrol agent of Pd in WNS affected sites.

Novel Trichoderma polysporum Strain for the Biocontrol of Pseudogymnoascus destructans, the Fungal Etiologic Agent of Bat White Nose Syndrome

PubMed Central

Zhang, Tao; Chaturvedi, Vishnu; Chaturvedi, Sudha

2015-01-01

White-nose syndrome (WNS), an emerging disease of hibernating bats, has rapidly spread across eastern North America killing millions of bats. Pseudogymnoascus destructans (Pd), the sole etiologic agent of WNS, is widespread and persistent in bat hibernacula. Control of Pd in the affected sites is urgently needed to break the transmission cycle while minimizing any adverse impact on the native organisms. We isolated a novel strain of Trichoderma polysporum (Tp) from one of the caves at the epicenter of WNS zoonotic. Detailed experimental studies revealed: (1) Tp WPM 39143 was highly adapted to grow at temperatures simulating the cave environment (6°C-15°C), (2) Tp WPM 39143 restricted Pd colony growth in dual culture challenges, (3) Tp WPM 39143 caused four logs reduction of Pd colony forming units and genome copies in autoclaved soil samples from one of the WNS affected caves, (4) Tp WPM 39143 extract showed specific fungicidal activity against Pd in disk diffusion assay, but not against closely related fungus P. pannorum (Pp), (5) Tp WPM 39143 extract retained inhibitory activity after exposure to high temperatures, light and proteinase K, and (6) Inhibitory metabolites in Tp WPM 39143 extract comprised of water-soluble, high polarity compounds. These results suggest that Tp WPM 39143 is a promising candidate for further evaluation as a biocontrol agent of Pd in WNS affected sites. PMID:26509269

Body size–trophic position relationships among fishes of the lower Mekong basin

PubMed Central

Montaña, Carmen G.; Winemiller, Kirk O.

2017-01-01

Body size is frequently claimed to be a major determinant of animal trophic interactions, yet few studies have explored relationships between body size and trophic interactions in rivers, especially within the tropics. We examined relationships between body size and trophic position (TP) within fish assemblages in four lowland rivers of the Lower Mekong Basin in Cambodia. Stable isotope analysis (based on δ15N) was used to estimate TP of common fish species in each river, and species were classified according to occupation of benthic versus pelagic habitats and major feeding guilds. Regression analysis yielded strong correlations between body size and TP among fishes from the Sesan and Sreprok rivers, but not those from the Mekong and Sekong rivers. The Mekong fish assemblage had higher average TP compared with those of other rivers. The relationship between body size and TP was positive and significantly correlated for piscivores and omnivores, but not for detritivores and insectivores. The body size–TP relationship did not differ between pelagic and benthic fishes. Body size significantly predicted TP within the orders Siluriformes and Perciformes, but not for Cypriniformes, the most species-rich and ecologically diverse order in the Lower Mekong River. We conclude that for species-rich, tropical fish assemblages with many detritivores and invertivores, body size would not be an appropriate surrogate for TP in food web models and other ecological applications. PMID:28280563

Protective effect of tea polyphenols against paracetamol-induced hepatotoxicity in mice is significantly correlated with cytochrome P450 suppression.

PubMed

Chen, Xia; Sun, Chang-Kai; Han, Guo-Zhu; Peng, Jin-Yong; Li, Ying; Liu, Yan-Xia; Lv, Yuan-Yuan; Liu, Ke-Xin; Zhou, Qin; Sun, Hui-Jun

2009-04-21

To investigate the hepatoprotective activity of tea polyphenols (TP) and its relation with cytochrome P450 (CYP450) expression in mice. Hepatic CYP450 and CYPb(5) levels were measured by UV-spectrophotometry in mice 2 d after intraperitoneal TP (25, 50 and 100 mg/kg per day). Then the mice were intragastricly pre-treated with TP (100, 200 and 400 mg/kg per day) for six days before paracetamol (1000 mg/kg) was given. Their acute mortality was compared with that of control mice. The mice were pre-treated with TP (100, 200, and 400 mg/kg per day) for five days before paracetamol (500 mg/kg) was given. Hepatic CYP2E1 and CYP1A2 protein and mRNA expression levels were evaluated by Western blotting, immunohistochemical staining and transcriptase-polymerase chain reaction. The hepatic CYP450 and CYPb(5) levels in mice of TP-treated groups (100, 200 and 400 mg/kg per day) were decreased in a dose-dependent manner compared with those in the negative control mice. TP significantly attenuated the paracetamol-induced hepatic injury and dramatically reduced the mortality of paracetamol-treated mice. Furthermore, TP reduced CYP2E1 and CYP1A2 expression at both protein and mRNA levels in a dose-dependent manner. TP possess potential hepatoprotective properties and can suppress CYP450 expression.

The Temporal Pole Top-Down Modulates the Ventral Visual Stream During Social Cognition.

PubMed

Pehrs, Corinna; Zaki, Jamil; Schlochtermeier, Lorna H; Jacobs, Arthur M; Kuchinke, Lars; Koelsch, Stefan

2017-01-01

The temporal pole (TP) has been associated with diverse functions of social cognition and emotion processing. Although the underlying mechanism remains elusive, one possibility is that TP acts as domain-general hub integrating socioemotional information. To test this, 26 participants were presented with 60 empathy-evoking film clips during fMRI scanning. The film clips were preceded by a linguistic sad or neutral context and half of the clips were accompanied by sad music. In line with its hypothesized role, TP was involved in the processing of sad context and furthermore tracked participants' empathic concern. To examine the neuromodulatory impact of TP, we applied nonlinear dynamic causal modeling to a multisensory integration network from previous work consisting of superior temporal gyrus (STG), fusiform gyrus (FG), and amygdala, which was extended by an additional node in the TP. Bayesian model comparison revealed a gating of STG and TP on fusiform-amygdalar coupling and an increase of TP to FG connectivity during the integration of contextual information. Moreover, these backward projections were strengthened by emotional music. The findings indicate that during social cognition, TP integrates information from different modalities and top-down modulates lower-level perceptual areas in the ventral visual stream as a function of integration demands. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Body size-trophic position relationships among fishes of the lower Mekong basin.

PubMed

Ou, Chouly; Montaña, Carmen G; Winemiller, Kirk O

2017-01-01

Body size is frequently claimed to be a major determinant of animal trophic interactions, yet few studies have explored relationships between body size and trophic interactions in rivers, especially within the tropics. We examined relationships between body size and trophic position (TP) within fish assemblages in four lowland rivers of the Lower Mekong Basin in Cambodia. Stable isotope analysis (based on δ 15 N) was used to estimate TP of common fish species in each river, and species were classified according to occupation of benthic versus pelagic habitats and major feeding guilds. Regression analysis yielded strong correlations between body size and TP among fishes from the Sesan and Sreprok rivers, but not those from the Mekong and Sekong rivers. The Mekong fish assemblage had higher average TP compared with those of other rivers. The relationship between body size and TP was positive and significantly correlated for piscivores and omnivores, but not for detritivores and insectivores. The body size-TP relationship did not differ between pelagic and benthic fishes. Body size significantly predicted TP within the orders Siluriformes and Perciformes, but not for Cypriniformes, the most species-rich and ecologically diverse order in the Lower Mekong River. We conclude that for species-rich, tropical fish assemblages with many detritivores and invertivores, body size would not be an appropriate surrogate for TP in food web models and other ecological applications.

TP Atlas: integration and dissemination of advances in Targeted Proteins Research Program (TPRP)-structural biology project phase II in Japan.

PubMed

Iwayanagi, Takao; Miyamoto, Sei; Konno, Takeshi; Mizutani, Hisashi; Hirai, Tomohiro; Shigemoto, Yasumasa; Gojobori, Takashi; Sugawara, Hideaki

2012-09-01

The Targeted Proteins Research Program (TPRP) promoted by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan is the phase II of structural biology project (2007-2011) following the Protein 3000 Project (2002-2006) in Japan. While the phase I Protein 3000 Project put partial emphasis on the construction and maintenance of pipelines for structural analyses, the TPRP is dedicated to revealing the structures and functions of the targeted proteins that have great importance in both basic research and industrial applications. To pursue this objective, 35 Targeted Proteins (TP) Projects selected in the three areas of fundamental biology, medicine and pharmacology, and food and environment are tightly collaborated with 10 Advanced Technology (AT) Projects in the four fields of protein production, structural analyses, chemical library and screening, and information platform. Here, the outlines and achievements of the 35 TP Projects are summarized in the system named TP Atlas. Progress in the diversified areas is described in the modules of Graphical Summary, General Summary, Tabular Summary, and Structure Gallery of the TP Atlas in the standard and unified format. Advances in TP Projects owing to novel technologies stemmed from AT Projects and collaborative research among TP Projects are illustrated as a hallmark of the Program. The TP Atlas can be accessed at http://net.genes.nig.ac.jp/tpatlas/index_e.html .

Adsorption on hydrophobic porous glass near the liquid/liquid coexistence curve of a binary liquid mixture

NASA Astrophysics Data System (ADS)

Grüll, H.; Woermann, D.

1997-01-01

A differential refractometric method is used to study the temperature and composition dependence of the adsorptive properties of porous glass in 2-butoxyethanol (abbreviated C4E1)/water mixtures. The surface of the adsorbent carries hydrophobic -SiO-C8H17 as well as hydrophilic -SiOH groups. The experiments are carried out close to the liquid/liquid coexistence curve in the vicinity of the lower critical point of the system. Depending on the temperature and composition of the mixtures either C4E1 or water is preferentially adsorbed. There exists a line along which the net adsorption vanishes. For compositions x>xc (x, mole fraction of C4E1; xc, critical composition) the amount of substance of adsorbed water ñ ws(Tp) per unit gram of adsorbent at temperature Tp increases with increasing values of the temperature difference (Tp-Tc) in the range 0 K<(Tp-Tc)<4 K. Tp is the temperature of phase separation of the bulk mixture in the presence of the adsorbent. Beginning at temperatures (Tp-Tc)>4 K the adsorbed amount of substance ñ ws(Tp) decreases. At (Tp-Tc)>8 K it reaches a value which is smaller by a factor of about 10 compared with its maximum value. This phenomenon is reminiscent of a wetting transition.

Combinatorial treatments enhance recovery following facial nerve crush.

PubMed

Sharma, Nijee; Moeller, Carl W; Marzo, Sam J; Jones, Kathryn J; Foecking, Eileen M

2010-08-01

To investigate the effects of various combinatorial treatments, consisting of a tapering dose of prednisone (P), a brief period of nerve electrical stimulation (ES), and systemic testosterone propionate (TP) on improving functional recovery following an intratemporal facial nerve crush injury. Prospective, controlled animal study. After a right intratemporal facial nerve crush, adult male Sprague-Dawley rats were divided into the following eight treatment groups: 1) no treatment, 2) P only, 3) ES only, 4) ES + P, 5) TP only, 6) TP + P, 7) ES + TP, and 8) ES + TP + P. For each group n = 4-8. Recovery of the eyeblink reflex and vibrissae orientation and movement were assessed. Changes in peak amplitude and latency of evoked response, in response to facial nerve stimulation, was also recorded weekly. : Brief ES of the proximal nerve stump most effectively accelerated the initiation of functional recovery. Also, ES or TP treatments enhanced recovery of some functional parameters more than P treatment. When administered alone, none of the three treatments improved recovery of complete facial function. Only the combinatorial treatment of ES + TP, regardless of the presence of P, accelerated complete functional recovery and return of normal motor nerve conduction. Our findings suggest that a combinatorial treatment strategy of using brief ES and TP together promises to be an effective therapeutic intervention for promoting regeneration following facial nerve injury. Administration of P neither augments nor hinders recovery.

TP53 alterations in pancreatic acinar cell carcinoma: new insights into the molecular pathology of this rare cancer.

PubMed

La Rosa, Stefano; Bernasconi, Barbara; Frattini, Milo; Tibiletti, Maria Grazia; Molinari, Francesca; Furlan, Daniela; Sahnane, Nora; Vanoli, Alessandro; Albarello, Luca; Zhang, Lizhi; Notohara, Kenji; Casnedi, Selenia; Chenard, Marie-Pierre; Adsay, Volkan; Asioli, Sofia; Capella, Carlo; Sessa, Fausto

2016-03-01

The molecular alterations of pancreatic acinar cell carcinomas (ACCs) are poorly understood and have been reported as being different from those in ductal adenocarcinomas. Loss of TP53 gene function in the pathogenesis of ACCs is controversial since contradictory findings have been published. A comprehensive analysis of the different possible genetic and epigenetic mechanisms leading to TP53 alteration in ACC has never been reported and hence the role of TP53 in the pathogenesis and/or progression of ACC remains unclear. We investigated TP53 alterations in 54 tumor samples from 44 patients, including primary and metastatic ACC, using sequencing analysis, methylation-specific multiplex ligation probe amplification, fluorescence in situ hybridization, and immunohistochemistry. TP53 mutations were found in 13 % of primary ACCs and in 31 % of metastases. Primary ACCs and metastases showed the same mutational profile, with the exception of one case, characterized by a wild-type sequence in the primary carcinoma and a mutation in the corresponding metastasis. FISH analysis revealed deletion of the TP53 region in 53 % of primary ACCs and in 50 % of metastases. Promoter hypermethylation was found in one case. The molecular alterations correlated well with the immunohistochemical findings. A statistically significant association was found between the combination of mutation of one allele and loss of the other allele of TP53 and worse survival.

The expression and clinical relevance of PD-1, PD-L1, and TP63 in patients with diffuse large B-cell lymphoma

PubMed Central

Fang, Xia; Xiu, Bing; Yang, Zhizhang; Qiu, Weizhe; Zhang, Long; Zhang, Suxia; Wu, Yunjin; Zhu, Xuyou; Chen, Xue; Xie, Suhong; Yi, Xianghua; Liang, Aibin; Zeng, Yu

2017-01-01

Abstract Latest study showed that a novel translocation between programmed cell death ligand 1 (PD-L1) (cluster of differentiation 274) and TP63 (tumor protein 63) can be found in diffuse large B-cell lymphoma (DLBCL), resulting in their conjunct overexpression in tumor cells at RNA level. However, the expressed pattern of these 2 genes at protein level in DLBCL remains largely unknown, and the clinical relevance of PD-L1 and TP63 expression in DLBCL are also unclear. Tumor tissues from 76 Chinese DLBCL patients were immunostained for programmed cell death 1 (PD-1), PD-L1, and TP63 using the EnVision system. Clinical relevance of PD-1, PD-L1, and TP63 in 74 DLBCL were analyzed by chi-square test, the Kaplan–Meier curves with log rank test, and Cox's proportional hazards regression model. PD-1 was mainly expressed in tumor-infiltrating lymphocytes (TILs) of 39.5% patients. PD-L1 was expressed in tumor cells of 26.3% patients, and TP63 was immunostained in nucleoli of tumor cells of 31.6% cases. PD-1 expression was significantly associated with the patients’ gender and B symptoms (P = 0.032, P = 0.026). DLBCL with PD-L1 or TP63 expression in tumor cells showed low International Prognostic Index (IPI) score (P = 0.007, P = 0.009). PD-1+ TILs was related to prolonged overall survival rate (OS) of DLBCL patients (P = 0.02), whereas PD-L1 expression was associated with worse clinical outcome of patients (P = 0.049). Immunoreactivity of TP63 was not correlated with patients’ survival time. Besides, PD-1 expression, patients’ age, Ann Arbor stage, and IPI score were significant prognostic markers for OS, but PD-L1 and TP63 had no prognostic significance. PD-1, PD-L1, and TP63 are frequently expressed in DLBCL. PD-1/PD-L1/TP63 blockade may be a potential therapeutic strategy for some patients. PMID:28403071

The expression and clinical relevance of PD-1, PD-L1, and TP63 in patients with diffuse large B-cell lymphoma.

PubMed

Fang, Xia; Xiu, Bing; Yang, Zhizhang; Qiu, Weizhe; Zhang, Long; Zhang, Suxia; Wu, Yunjin; Zhu, Xuyou; Chen, Xue; Xie, Suhong; Yi, Xianghua; Liang, Aibin; Zeng, Yu

2017-04-01

Latest study showed that a novel translocation between programmed cell death ligand 1 (PD-L1) (cluster of differentiation 274) and TP63 (tumor protein 63) can be found in diffuse large B-cell lymphoma (DLBCL), resulting in their conjunct overexpression in tumor cells at RNA level. However, the expressed pattern of these 2 genes at protein level in DLBCL remains largely unknown, and the clinical relevance of PD-L1 and TP63 expression in DLBCL are also unclear.Tumor tissues from 76 Chinese DLBCL patients were immunostained for programmed cell death 1 (PD-1), PD-L1, and TP63 using the EnVision system. Clinical relevance of PD-1, PD-L1, and TP63 in 74 DLBCL were analyzed by chi-square test, the Kaplan-Meier curves with log rank test, and Cox's proportional hazards regression model.PD-1 was mainly expressed in tumor-infiltrating lymphocytes (TILs) of 39.5% patients. PD-L1 was expressed in tumor cells of 26.3% patients, and TP63 was immunostained in nucleoli of tumor cells of 31.6% cases. PD-1 expression was significantly associated with the patients' gender and B symptoms (P = 0.032, P = 0.026). DLBCL with PD-L1 or TP63 expression in tumor cells showed low International Prognostic Index (IPI) score (P = 0.007, P = 0.009). PD-1 TILs was related to prolonged overall survival rate (OS) of DLBCL patients (P = 0.02), whereas PD-L1 expression was associated with worse clinical outcome of patients (P = 0.049). Immunoreactivity of TP63 was not correlated with patients' survival time. Besides, PD-1 expression, patients' age, Ann Arbor stage, and IPI score were significant prognostic markers for OS, but PD-L1 and TP63 had no prognostic significance.PD-1, PD-L1, and TP63 are frequently expressed in DLBCL. PD-1/PD-L1/TP63 blockade may be a potential therapeutic strategy for some patients.

Molecular cloning and characterization of leucine aminopeptidase gene from Taenia pisiformis.

PubMed

Zhang, Shaohua; Cai, Xuepeng; Luo, Xuenong; Wang, Shuai; Guo, Aijiang; Hou, Junling; Wu, Run

2018-03-01

Leucine aminopeptidase (LAP, EC: 3.4.11.1) is an important metalloexopeptidase that catalyze the hydrolysis of amino-terminal leucine residues from polypeptides and proteins. In this study, a full length of cDNA encoding leucine aminopeptidase of Taenia pisiformis (TpLAP) was cloned by rapid amplification of cDNA-ends using the polymerase chain reaction (RACE-PCR) method. The full-length cDNA of the TpLAP gene is 1823 bp and contains a 1569 bp ORF encoding 533 amino acids with a putative mass of 56.4 kDa. TpLAP contains two characteristic motifs of the M17LAP family in the C-terminal sequence: the metal binding site 265-[VGKG]-271 and the catalytic domain motif 351-[NTDAEGRL]-357. The soluble GST-TpLAP protein was expressed in Escherichia coli Transetta (DE3) and four specific anti-TpLAP monoclonal antibodies (mAbs) were prepared. In enzymatic assays, the optimal activity was observed at pH 9.5 at 45 °C. GST-TpLAP displayed a hydrolyzing activity for the Leu-pNA substrate with a maximum activity of 46 U/ml. The enzymatic activity was significantly enhanced by Mn 2+ and completely inhibited by 20 nM bestatin and 0.15 mM EDTA. The native TpLAP was detected specifically in ES components of adult T. pisiformis by western blotting using anti-TpLAP mAb as a probe. Quantitative real-time PCR revealed that the TpLAP gene was expressed at a high level in adult worm tissues, especially in the gravid proglottids (50.71-fold). Immunolocalization analysis showed that TpLAP was located primarily in the subtegumental parenchyma zone and the uterine wall of adult worms. Our results indicate that TpLAP is a new member of the M17LAP family and can be considered as a stage-differentially expressed protein. These findings might provide new insights into the study of the mechanisms of growth, development and survival of T. pisiformis in the final host and have potential value as an attractive target for drug therapy or vaccine intervention. Copyright © 2018 Elsevier Inc. All rights reserved.

Marathon Kids UK: study design and protocol for a mixed methods evaluation of a school-based running programme.

PubMed

Chalkley, Anna E; Routen, Ash C; Harris, Jo P; Cale, Lorraine A; Gorely, Trish; Sherar, Lauren B

2018-05-14

Schools are promising settings for physical activity promotion; however, they are complex and adaptive systems that can influence the quality of programme implementation. This paper presents an evaluation of a school-based running programme (Marathon Kids). The aims of this study are (1) to identify the processes by which schools implement the programme, (2) identify and explain the contextual factors affecting implementation and explications of effectiveness and (3) examine the relationship between the level of implementation and perceived outcomes. Using a realist evaluation framework, a mixed method single-group before-and-after design, strengthened by multiple interim measurements, will be used. Year 5 (9-10 years old) pupils and their teachers will be recruited from six state-funded primary schools in Leicestershire, UK.Data will be collected once prior to implementation, at five discrete time points during implementation and twice following implementation. A weekly implementation log will also be used. At time point 1 (TP1) (September 2016), data on school environment, teacher and pupil characteristics will be collected. At TP1 and TP6 (July 2017), accelerometry, pupil self-reported physical activity and psychosocial data (eg, social support and intention to be active) will be collected. At TP2, TP3 and TP5 (January, March and June 2017), observations will be conducted. At TP2 and TP5, there will be teacher interviews and pupil focus groups. Follow-up teacher interviews will be conducted at TP7 and TP8 (October 2017 and March 2018) and pupil focus group at TP8. In addition, synthesised member checking will be conducted (June 2018) with a mixed sample of schools. Ethical approval for this study was obtained through Loughborough University Human Participants Ethics Subcommittee (R16-P032 & R16-P116). Findings will be disseminated via print, online media and dissemination events as well as practitioner and/or research journals. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Wetting and greening Tibetan Plateau in early summer since the late 1970s due to advanced Asian summer monsoon onset

NASA Astrophysics Data System (ADS)

Zhang, Wenxia; Zhou, Tianjun; Zhang, Lixia

2016-04-01

Known as the "the world water tower", the Tibetan Plateau (TP) is the origin of the ten largest rivers in Asia, breeding more than 1.4 billion people, and exerts substantial influences on water resources, agriculture, and ecosystems in downstream countries. This region is one of the most susceptible areas around the world to changing climate due to the high elevation. Observed evidence have shown significant climate changes over the TP, including surface air warming and moistening, glaciers shrinking, winds stilling, solar dimming, and atmospheric heat source weakening. However, as an essential part of the hydrological cycle, precipitation changes on the TP remain an ambiguous picture. Changes in precipitation vary largely with different seasons, time periods and climate zones considered. This study shows a robust increase in precipitation amount over the TP in May, when the rainy season starts, over the period 1979-2014 (31% relative to the climatology). The wetting trend is spatially consistent over the south-eastern TP, to which both precipitation frequency and intensity contribute. Circulation trends show that the wetting TP in May is resulted from the advanced onset of Asian summer monsoon, which onsets 1~2 pentads earlier since 1979. It intensified water vapor transport from the Bay of Bengal (BOB) to south of the TP in May and local anomalous convection. This relationship is further validated by the significant correlation coefficient (0.47) between the onset dates of Asian summer monsoon (particularly the BOB summer monsoon, 0.68) and precipitation over the south-eastern TP in May. The wetting TP in May has further exerted profound impacts on the hydrological cycle and ecosystem, such as moistening the soil and animating vegetation activities throughout early summer. Both decadal variations of soil moisture (from May to June) and Normalized Difference Vegetation Index (NDVI) (from May to July) coincide well with that of precipitation over the south-eastern TP, significant at 99% confidence level by Mann-Kendall test. This implies that the increasing precipitation in May is favoring a greening TP throughout early summer, benefitting a more favorable ecological environment in the semi-humid region there.

Remote sensing estimation of the total phosphorus concentration in a large lake using band combinations and regional multivariate statistical modeling techniques.

PubMed

Gao, Yongnian; Gao, Junfeng; Yin, Hongbin; Liu, Chuansheng; Xia, Ting; Wang, Jing; Huang, Qi

2015-03-15

Remote sensing has been widely used for ater quality monitoring, but most of these monitoring studies have only focused on a few water quality variables, such as chlorophyll-a, turbidity, and total suspended solids, which have typically been considered optically active variables. Remote sensing presents a challenge in estimating the phosphorus concentration in water. The total phosphorus (TP) in lakes has been estimated from remotely sensed observations, primarily using the simple individual band ratio or their natural logarithm and the statistical regression method based on the field TP data and the spectral reflectance. In this study, we investigated the possibility of establishing a spatial modeling scheme to estimate the TP concentration of a large lake from multi-spectral satellite imagery using band combinations and regional multivariate statistical modeling techniques, and we tested the applicability of the spatial modeling scheme. The results showed that HJ-1A CCD multi-spectral satellite imagery can be used to estimate the TP concentration in a lake. The correlation and regression analysis showed a highly significant positive relationship between the TP concentration and certain remotely sensed combination variables. The proposed modeling scheme had a higher accuracy for the TP concentration estimation in the large lake compared with the traditional individual band ratio method and the whole-lake scale regression-modeling scheme. The TP concentration values showed a clear spatial variability and were high in western Lake Chaohu and relatively low in eastern Lake Chaohu. The northernmost portion, the northeastern coastal zone and the southeastern portion of western Lake Chaohu had the highest TP concentrations, and the other regions had the lowest TP concentration values, except for the coastal zone of eastern Lake Chaohu. These results strongly suggested that the proposed modeling scheme, i.e., the band combinations and the regional multivariate statistical modeling techniques, demonstrated advantages for estimating the TP concentration in a large lake and had a strong potential for universal application for the TP concentration estimation in large lake waters worldwide. Copyright © 2014 Elsevier Ltd. All rights reserved.

Optimized p53 immunohistochemistry is an accurate predictor of TP53 mutation in ovarian carcinoma.

PubMed

Köbel, Martin; Piskorz, Anna M; Lee, Sandra; Lui, Shuhong; LePage, Cecile; Marass, Francesco; Rosenfeld, Nitzan; Mes Masson, Anne-Marie; Brenton, James D

2016-10-01

TP53 mutations are ubiquitous in high-grade serous ovarian carcinomas (HGSOC), and the presence of TP53 mutation discriminates between high and low-grade serous carcinomas and is now an important biomarker for clinical trials targeting mutant p53. p53 immunohistochemistry (IHC) is widely used as a surrogate for TP53 mutation but its accuracy has not been established. The objective of this study was to test whether improved methods for p53 IHC could reliably predict TP53 mutations independently identified by next generation sequencing (NGS). Four clinical p53 IHC assays and tagged-amplicon NGS for TP53 were performed on 171 HGSOC and 80 endometrioid carcinomas (EC). p53 expression was scored as overexpression (OE), complete absence (CA), cytoplasmic (CY) or wild type (WT). p53 IHC was evaluated as a binary classifier where any abnormal staining predicted deleterious TP53 mutation and as a ternary classifier where OE, CA or WT staining predicted gain-of-function (GOF or nonsynonymous), loss-of-function (LOF including stopgain, indel, splicing) or no detectable TP53 mutations (NDM), respectively. Deleterious TP53 mutations were detected in 169/171 (99%) HGSOC and 7/80 (8.8%) EC. The overall accuracy for the best performing IHC assay for binary and ternary prediction was 0.94 and 0.91 respectively, which improved to 0.97 (sensitivity 0.96, specificity 1.00) and 0.95 after secondary analysis of discordant cases. The sensitivity for predicting LOF mutations was lower at 0.76 because p53 IHC detected mutant p53 protein in 13 HGSOC with LOF mutations. CY staining associated with LOF was seen in 4 (2.3%) of HGSOC. Optimized p53 IHC can approach 100% specificity for the presence of TP53 mutation and its high negative predictive value is clinically useful as it can exclude the possibility of a low-grade serous tumour. 4.1% of HGSOC cases have detectable WT staining while harboring a TP53 LOF mutation, which limits sensitivity for binary prediction of mutation to 96%.

Optimized p53 immunohistochemistry is an accurate predictor of TP53 mutation in ovarian carcinoma

PubMed Central

Köbel, Martin; Piskorz, Anna M; Lee, Sandra; Lui, Shuhong; LePage, Cecile; Marass, Francesco; Rosenfeld, Nitzan; Mes Masson, Anne‐Marie

2016-01-01

Abstract TP53 mutations are ubiquitous in high‐grade serous ovarian carcinomas (HGSOC), and the presence of TP53 mutation discriminates between high and low‐grade serous carcinomas and is now an important biomarker for clinical trials targeting mutant p53. p53 immunohistochemistry (IHC) is widely used as a surrogate for TP53 mutation but its accuracy has not been established. The objective of this study was to test whether improved methods for p53 IHC could reliably predict TP53 mutations independently identified by next generation sequencing (NGS). Four clinical p53 IHC assays and tagged‐amplicon NGS for TP53 were performed on 171 HGSOC and 80 endometrioid carcinomas (EC). p53 expression was scored as overexpression (OE), complete absence (CA), cytoplasmic (CY) or wild type (WT). p53 IHC was evaluated as a binary classifier where any abnormal staining predicted deleterious TP53 mutation and as a ternary classifier where OE, CA or WT staining predicted gain‐of‐function (GOF or nonsynonymous), loss‐of‐function (LOF including stopgain, indel, splicing) or no detectable TP53 mutations (NDM), respectively. Deleterious TP53 mutations were detected in 169/171 (99%) HGSOC and 7/80 (8.8%) EC. The overall accuracy for the best performing IHC assay for binary and ternary prediction was 0.94 and 0.91 respectively, which improved to 0.97 (sensitivity 0.96, specificity 1.00) and 0.95 after secondary analysis of discordant cases. The sensitivity for predicting LOF mutations was lower at 0.76 because p53 IHC detected mutant p53 protein in 13 HGSOC with LOF mutations. CY staining associated with LOF was seen in 4 (2.3%) of HGSOC. Optimized p53 IHC can approach 100% specificity for the presence of TP53 mutation and its high negative predictive value is clinically useful as it can exclude the possibility of a low‐grade serous tumour. 4.1% of HGSOC cases have detectable WT staining while harboring a TP53 LOF mutation, which limits sensitivity for binary prediction of mutation to 96%. PMID:27840695

Role of vasopressin and terlipressin in refractory shock compared to conventional therapy in the neonatal and pediatric population: a systematic review, meta-analysis, and trial sequential analysis.

PubMed

Masarwa, Reem; Paret, Gideon; Perlman, Amichai; Reif, Shimon; Raccah, Bruria Hirsh; Matok, Ilan

2017-01-05

Vasopressin (AVP) and terlipressin (TP) have been used as last-line therapy in refractory shock in children. However, the efficacy and safety profiles of AVP and TP have not been determined in pediatric refractory shock of different origins. We aimed to assess the efficacy and safety of the addition of AVP/TP therapy in pediatric refractory shock of all causes compared to conventional therapy with fluid resuscitation and vasopressor and inotropic therapy. We conducted a systematic review, meta-analysis, and trial sequential analysis (TSA) comparing AVP and TP to conventional therapy. MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov were searched up to February 2016. The systematic review included all reports of AVP/TP use in the pediatric population. Reports of clinical trials were pooled using random-effects models and TSA. Main outcomes were mortality and tissue ischemia. Three randomized controlled trials and five "before-and-after clinical" trials (without comparator) met the inclusion criteria. Among 224 neonates and children (aged 0 to 18 years) with refractory shock, 152 received therapy with AVP or TP. Pooled analyses showed no association between AVP/TP treatment and mortality (relative risk (RR),1.19; 95% confidence interval (CI), 0.71-2.00), length of stay in the pediatric intensive care unit (PICU) (mean difference (MD), -3.58 days; 95% CI, -9.05 to 1.83), and tissue ischemia (RR, 1.48; 95% CI, 0.47-4.62). In TSA, no significant effect on mortality and risk for developing tissue ischemia was observed with AVP/TP therapy. Our results emphasize the lack of observed benefit for AVP/TP in terms of mortality and length of stay in the PICU, and suggest an increased risk for ischemic events. Our TSA suggests that further large studies are necessary to demonstrate and establish benefits of AVP/TP in children. PROSPERO registry: CRD42016035872.

Push pull microfluidics on a multi-level 3D CD.

PubMed

Thio, Tzer Hwai Gilbert; Ibrahim, Fatimah; Al-Faqheri, Wisam; Moebius, Jacob; Khalid, Noor Sakinah; Soin, Norhayati; Kahar, Maria Kahar Bador Abdul; Madou, Marc

2013-08-21

A technique known as thermo-pneumatic (TP) pumping is used to pump fluids on a microfluidic compact disc (CD) back towards the CD center against the centrifugal force that pushes liquids from the center to the perimeter of the disc. Trapped air expands in a TP air chamber during heating, and this creates positive pressure on liquids located in chambers connected to that chamber. While the TP air chamber and connecting channels are easy to fabricate in a one-level CD manufacturing technique, this approach provides only one way pumping between two chambers, is real-estate hungry and leads to unnecessary heating of liquids in close proximity to the TP chamber. In this paper, we present a novel TP push and pull pumping method which allows for pumping of liquid in any direction between two connected liquid chambers. To ensure that implementation of TP push and pull pumping also addresses the issue of space and heating challenges, a multi-level 3D CD design is developed, and localized forced convection heating, rather than infra-red (IR) is applied. On a multi-level 3D CD, the TP features are placed on a top level separate from the rest of the microfluidic processes that are implemented on a lower separate level. This approach allows for heat shielding of the microfluidic process level, and efficient usage of space on the CD for centrifugal handling of liquids. The use of localized forced convection heating, rather than infra-red (IR) or laser heating in earlier implementations allows not only for TP pumping of liquids while the CD is spinning but also makes heat insulation for TP pumping and other fluidic functions easier. To aid in future implementations of TP push and pull pumping on a multi-level 3D CD, study on CD surface heating is also presented. In this contribution, we also demonstrate an advanced application of pull pumping through the implementation of valve-less switch pumping.

Critical androgen-sensitive periods of rat penis and clitoris development.

PubMed

Welsh, Michelle; MacLeod, David J; Walker, Marion; Smith, Lee B; Sharpe, Richard M

2010-02-01

Androgen control of penis development/growth is unclear. In rats, androgen action in a foetal 'masculinisation programming window' (MPW; e15.5-e18.5)' predetermines penile length and hypospadias occurrence. This has implications for humans (e.g. micropenis). Our studies aimed to establish in rats when androgen action/administration affects development/growth of the penis and if deficits in MPW androgen action were rescuable postnatally. Thus, pregnant rats were treated with flutamide during the MPW +/- postnatal testosterone propionate (TP) treatment. To assess penile growth responsiveness, rats were treated with TP in various time windows (late foetal, neonatal through early puberty, puberty onset, or combinations thereof). Phallus length, weight, and morphology, hypospadias and anogenital distance (AGD) were measured in mid-puberty (d25) or adulthood (d90) in males and females, plus serum testosterone in adult males. MPW flutamide exposure reduced adult penile length and induced hypospadias dose-dependently; this was not rescued by postnatal TP treatment. In normal rats, foetal (e14.5-e21.5) TP exposure did not affect male penis size but increased female clitoral size. In males, TP exposure from postnatal d1-24 or at puberty (d15-24), increased penile length at d25, but not ultimately in adulthood. Foetal + postnatal TP (e14-postnatal d24) increased penile size at d25 but reduced it at d90 (due to reduced endogenous testosterone). In females, this treatment caused the biggest increase in adult clitoral size but, unlike in males, phallus size was unaffected by TP during puberty (d15-24). Postnatal TP treatment advanced penile histology at d25 to more resemble adult histology. AGD strongly correlated with final penis length. It is concluded that adult penile size depends critically on androgen action during the MPW but subsequent growth depends on later androgen exposure. Foetal and/or postnatal TP exposure does not increase adult penile size above its 'predetermined' length though its growth towards this maximum is advanced by peripubertal TP treatment.

[Inversion Model and Daily Variation of Total Phosphorus Concentrations in Taihu Lake Based on GOCI Data].

PubMed

Du, Cheng-gong; Li, Yun-mei; Wang, Qiao; Zhu, Li; Lü, Heng

2016-03-15

The TP concentration is an important index of water quality and an important influencing factor of eutrophication and algae blooms. Remote sensing technology has advantages of wide scope and high time limited efficacy. Monitoring the concentration of TP by satellite remote sensing is important for the study of water quality and eutrophication. In situ datasets collected during the three times of experiments in Taihu Lake between 2013 and 2014 were used to develop the TP inversion model based on GOCI data. The GOCI data in spring, summer, autumn and winter in 2014 were selected to analyze the time and space changes of TP concentration in Taihu Lake. The results showed that the TP algorithm was built up based on the variables, which was to use the eight band combination of GOCI data as variable, and build model using Multi factor linear regression method. The algorithm achieved more accurate TP estimation with R² = 0.898, MAPE = 14.296%, RMSE = 0.026 mg · L⁻¹. Meantime, a analysis on the precision of the model by using the measured sample points and the synchronous satellite images with MAPE = 33.642%, 22.551%, RMSE = 0.076 mg · L⁻¹, 0.028 mg · L⁻¹ on August 5, 2014 and October 24, 2014. Through the analysis of the 30 images on the four days of the four seasons, it showed that the absolute concentration of total phosphorus was different in different seasons. But temporal and spatial distribution of total phosphorus concentration was similar in the morning and afternoon. In spatial distribution, the TP concentration in Meiliang Bay, Zhushan Bay, Gonghu Bay, Xiaomei Port and Changdou Port in the southwest coast was at a continuously high position. The TP concentration change in different regions was influenced by wind direction, wind speed and other factors. The TP concentration highest in the morning, and then gradually decreased, this phenomenon reflected that the TP concentration was affected by temperature and light.

TP53-based interaction analysis identifies cis-eQTL variants for TP53BP2, FBXO28, and FAM53A that associate with survival and treatment outcome in breast cancer

PubMed Central

Fagerholm, Rainer; Khan, Sofia; Schmidt, Marjanka K.; GarcClosas, Montserrat; Heikkilä, Päivi; Saarela, Jani; Beesley, Jonathan; Jamshidi, Maral; Aittomäki, Kristiina; Liu, Jianjun; Raza Ali, H.; Andrulis, Irene L.; Beckmann, Matthias W.; Behrens, Sabine; Blows, Fiona M.; Brenner, Hermann; Chang-Claude, Jenny; Couch, Fergus J.; Czene, Kamila; Fasching, Peter A.; Figueroa, Jonine; Floris, Giuseppe; Glendon, Gord; Guo, Qi; Hall, Per; Hallberg, Emily; Hamann, Ute; Holleczek, Bernd; Hooning, Maartje J.; Hopper, John L.; Jager, Agnes; Kabisch, Maria; Investigators, kConFab/AOCS; Keeman, Renske; Kosma, Veli-Matti; Lambrechts, Diether; Lindblom, Annika; Mannermaa, Arto; Margolin, Sara; Provenzano, Elena; Shah, Mitul; Southey, Melissa C.; Dennis, Joe; Lush, Michael; Michailidou, Kyriaki; Wang, Qin; Bolla, Manjeet K.; Dunning, Alison M.; Easton, Douglas F.; Pharoah, Paul D.P .; Chenevix-Trench, Georgia; Blomqvist, Carl; Nevanlinna, Heli

2017-01-01

TP53 overexpression is indicative of somatic TP53 mutations and associates with aggressive tumors and poor prognosis in breast cancer. We utilized a two-stage SNP association study to detect variants associated with breast cancer survival in a TP53-dependent manner. Initially, a genome-wide study (n = 575 cases) was conducted to discover candidate SNPs for genotyping and validation in the Breast Cancer Association Consortium (BCAC). The SNPs were then tested for interaction with tumor TP53 status (n = 4,610) and anthracycline treatment (n = 17,828). For SNPs interacting with anthracycline treatment, siRNA knockdown experiments were carried out to validate candidate genes. In the test for interaction between SNP genotype and TP53 status, we identified one locus, represented by rs10916264 (p(interaction) = 3.44 05E010-5; FDR-adjusted p = 0.0011) in estrogen receptor (ER) positive cases. The rs10916264 AA genotype associated with worse survival among cases with ER-positive, TP53-positive tumors (hazard ratio [HR] 2.36, 95% confidence interval [C.I] 1.45 - 3.82). This is a cis-eQTL locus for FBXO28 and TP53BP2; expression levels of these genes were associated with patient survival specifically in ER-positive, TP53-mutated tumors. Additionally, the SNP rs798755 was associated with survival in interaction with anthracycline treatment (p(interaction) = 9.57 05E010-5, FDR-adjusted p = 0.0130). RNAi-based depletion of a predicted regulatory target gene, FAM53A, indicated that this gene can modulate doxorubicin sensitivity in breast cancer cell lines. If confirmed in independent data sets, these results may be of clinical relevance in the development of prognostic and predictive marker panels for breast cancer. PMID:28179588

Advanced Running Performance by Genetic Predisposition in Male Dummerstorf Marathon Mice (DUhTP) Reveals Higher Sterol Regulatory Element-Binding Protein (SREBP) Related mRNA Expression in the Liver and Higher Serum Levels of Progesterone

PubMed Central

Brenmoehl, Julia; Walz, Christina; Ponsuksili, Siriluck; Schwerin, Manfred; Fuellen, Georg; Hoeflich, Andreas

2016-01-01

Long-term-selected DUhTP mice represent a non-inbred model for inborn physical high-performance without previous training. Abundance of hepatic mRNA in 70-day male DUhTP and control mice was analyzed using the Affymetrix mouse array 430A 2.0. Differential expression analysis with PLIER corrected data was performed using AltAnalyze. Searching for over-representation in biochemical pathways revealed cholesterol metabolism being most prominently affected in DUhTP compared to unselected control mice. Furthermore, pathway analysis by AltAnalyze plus PathVisio indicated significant induction of glycolysis, fatty acid synthesis and cholesterol biosynthesis in the liver of DUhTP mice versus unselected control mice. In contrast, gluconeogenesis was partially inactivated as judged from the analysis of hepatic mRNA transcript abundance in DUhTP mice. Analysis of mRNA transcripts related to steroid hormone metabolism inferred elevated synthesis of progesterone and reduced levels of sex steroids. Abundance of steroid delta isomerase-5 mRNA (Hsd3b5, FC 4.97) was increased and steroid 17-alpha-monooxygenase mRNA (Cyp17a1, FC -11.6) was massively diminished in the liver of DUhTP mice. Assessment of steroid profiles by LC-MS revealed increased levels of progesterone and decreased levels of sex steroids in serum from DUhTP mice versus controls. Analysis of hepatic mRNA transcript abundance indicates that sterol regulatory element-binding protein-1 (SREBP-1) may play a major role in metabolic pathway activation in the marathon mouse model DUhTP. Thus, results from bioinformatics modeling of hepatic mRNA transcript abundance correlated with direct steroid analysis by mass spectrometry and further indicated functions of SREBP-1 and steroid hormones for endurance performance in DUhTP mice. PMID:26799318

Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo.

PubMed

Zhang, Li; Wang, Tengteng; Li, Qiang; Huang, Jing; Xu, Hao; Li, Jinlong; Wang, Yongjun; Liang, Qianqian

2016-01-01

Triptolide (TP) displays a strong immunosuppression function in immune-mediated diseases, especially in the treatment of rheumatoid arthritis. However, in addition to its medical and health-related functions, TP also exhibits diverse pharmacological side effects, for instance, liver and kidney toxicity and myelosuppression. In order to reduce the side effects, a nano drug carrier system (γ-PGA-l-PAE-TP [PPT]), in which TP was loaded by a poly-γ-glutamic acid-grafted l-phenylalanine ethylester copolymer, was developed. PPT was characterized by photon scattering correlation spectroscopy and transmission electron microscopy, which demonstrated that the average diameter of the drug carrier system is 98±15 nm, the polydispersity index is 0.18, the zeta potential is -35 mV, and the TP encapsulation efficiency is 48.6% with a controlled release manner. The methylthiazolyldiphenyl-tetrazolium bromide assay and flow cytometry revealed that PPT could decrease toxicity and apoptosis induced by free TP on RAW264.7 cells, respectively. The detection of reactive oxygen species showed that PPT could decrease the cellular reactive oxygen species induced by TP. Compared with the free TP-treated group, PPT improved the survival rate of the mice (P<0.01) and had no side effects or toxic effects on the thymus index (P>0.05) and spleen index (P>0.05). The blood biochemical indexes revealed that PPT did not cause much damage to the kidney (blood urea nitrogen and creatinine), liver (serum alanine aminotransferase and aspartate aminotransferase), or blood cells (P>0.05). Meanwhile, hematoxylin and eosin staining and terminal-deoxynucleotidyl transferase dUTP nick-end labeling staining indicated that PPT reduced the damage of free TP on the liver, kidney, and spleen. Our results demonstrated that PPT reduced free TP toxicity in vitro and in vivo and that it is a promising fundamental drug delivery system for rheumatoid arthritis treatment.

Push pull microfluidics on a multi-level 3D CD

PubMed Central

Thio, Tzer Hwai Gilbert; Ibrahim, Fatimah; Al-Faqheri, Wisam; Moebius, Jacob; Khalid, Noor Sakinah; Soin, Norhayati; Kahar, Maria Kahar Bador Abdul; Madou, Marc

2013-01-01

A technique known as thermo-pneumatic (TP) pumping is used to pump fluids on a microfluidic compact disc (CD) back towards the CD center against the centrifugal force that pushes liquids from the center to the perimeter of the disc. Trapped air expands in a TP air chamber during heating, and this creates positive pressure on liquids located in chambers connected to that chamber. While the TP air chamber and connecting channels are easy to fabricate in a one-level CD manufacturing technique, this approach provides only one way pumping between two chambers, is real-estate hungry and leads to unnecessary heating of liquids in close proximity to the TP chamber. In this paper, we present a novel TP push and pull pumping method which allows for pumping of liquid in any direction between two connected liquid chambers. To ensure that implementation of TP push and pull pumping also addresses the issue of space and heating challenges, a multi-level 3D CD design is developed, and localized forced convection heating, rather than infra-red (IR) is applied. On a multi-level 3D CD, the TP features are placed on a top level separate from the rest of the microfluidic processes that are implemented on a lower separate level. This approach allows for heat shielding of the microfluidic process levels, and efficient usage of space on the CD for centrifugal handling of liquids. The use of localized forced convection heating, rather than infra-red (IR) or laser heating in earlier implementations allows not only for TP pumping of liquids while the CD is spinning but also makes heat insulation for TP pumping and other fluidic functions easier. To aid in future implementations of TP push and pull pumping on a multi-level 3D CD, study on CD surface heating is also presented. In this contribution, we also demonstrate an advanced application of pull pumping through the implementation of valve-less switch pumping. PMID:23774994

The assessment of P-wave dispersion and myocardial repolarization parameters in patients with chronic kidney disease.

PubMed

Kollu, Korhan; Altintepe, Lutfullah; Duran, Cevdet; Topal, Mustafa; Ecirli, Samil

2018-11-01

The risks of sudden death and cardiac arrhythmia are increased in patients with chronic kidney disease (CKD). Here, we aimed to evaluate the indicators of arrhythmias, such as p-wave dispersion (P-WD), QTc dispersion, Tp-e and Tp-e/QT ratio in patients with CKD stages 3-5 on no renal replacement therapy (RRT). One-hundred and thirty three patients with CKD stages 3-5 and 32 healthy controls were enrolled into the study. No patients received RRT. QTc dispersion, P-WD and Tp-e interval were measured using electrocardiogram and Tp-e/QT ratio was also calculated. Mean age rates were found similar in patients and controls (60.8 ± 14.2 and 61 ± 12.9 y, p = .937, respectively). Compared patients with controls, P-WD (45.85 ± 12.42 vs. 21.17 ± 6.6 msec, p < .001), QTc-min (366.99 ± 42.31 vs. 387.15 ± 20.5 msec, p < .001), QTc dispersion (71.13 ± 27.95 vs. 41.25 ± 14.55 msec, p < .001), Tp-e maximum (81.04 ± 10.34 vs. 75.49 ± 10.9 msec, p < .001), Tp-e minimum (62.25 ± 7.58 vs. 54.8 ± 6.72 msec, p < .001) and Tp-e/QTc ratio (0.19 ± 0.02 vs. 0.18 ± 0.01, p = .001) were found to be different. QTc-max and Tp-e interval were found to be similar in both groups. P-WD and QTc dispersion, Tp-e interval and Tp-e/QTc ratio were found to be increased in with CKD stages 3-5 on no RRT.

Genes encoding two Theileria parva antigens recognized by CD8+ T-cells exhibit sequence diversity in South Sudanese cattle populations but the majority of alleles are similar to the Muguga component of the live vaccine cocktail

PubMed Central

Pelle, Roger; Mwacharo, Joram M.; Njahira, Moses N.; Marcellino, Wani L.; Kiara, Henry; Malak, Agol K.; EL Hussein, Abdel Rahim M.; Bishop, Richard; Skilton, Robert A.

2017-01-01

East Coast fever (ECF), caused by Theileria parva infection, is a frequently fatal disease of cattle in eastern, central and southern Africa, and an emerging disease in South Sudan. Immunization using the infection and treatment method (ITM) is increasingly being used for control in countries affected by ECF, but not yet in South Sudan. It has been reported that CD8+ T-cell lymphocytes specific for parasitized cells play a central role in the immunity induced by ITM and a number of T. parva antigens recognized by parasite-specific CD8+ T-cells have been identified. In this study we determined the sequence diversity among two of these antigens, Tp1 and Tp2, which are under evaluation as candidates for inclusion in a sub-unit vaccine. T. parva samples (n = 81) obtained from cattle in four geographical regions of South Sudan were studied for sequence polymorphism in partial sequences of the Tp1 and Tp2 genes. Eight positions (1.97%) in Tp1 and 78 positions (15.48%) in Tp2 were shown to be polymorphic, giving rise to four and 14 antigen variants in Tp1 and Tp2, respectively. The overall nucleotide diversity in the Tp1 and Tp2 genes was π = 1.65% and π = 4.76%, respectively. The parasites were sampled from regions approximately 300 km apart, but there was limited evidence for genetic differentiation between populations. Analyses of the sequences revealed limited numbers of amino acid polymorphisms both overall and in residues within the mapped CD8+ T-cell epitopes. Although novel epitopes were identified in the samples from South Sudan, a large number of the samples harboured several epitopes in both antigens that were similar to those in the T. parva Muguga reference stock, which is a key component in the widely used live vaccine cocktail. PMID:28231338

LncRNA-TP53TG1 Participated in the Stress Response Under Glucose Deprivation in Glioma.

PubMed

Chen, Xin; Gao, Yang; Li, Deheng; Cao, Yiqun; Hao, Bin

2017-12-01

Gliomas are the most common brain tumors of the center nervous system. And long non-coding RNAs (lncRNAs) are non-protein coding transcripts, which have been considered as one type of gene expression regulator for cancer development. In this study, we investigated the role of lncRNA-TP53TG1 in response to glucose deprivation in human gliomas. The expression levels of TP53TG1 in glioma tissues and cells were analyzed by qRT-PCR. In addition, the influence of TP53TG1 on glucose metabolism related genes at the mRNA level during both high and low glucose treatment was detected by qRT-PCR. MTT, clonogenicity assays, and flow cytometry were performed to detect the cell proliferation and cell apoptosis. Furthermore, the migration of glioma cells was examined by Transwell assays. The expression of TP53TG1 was significantly higher in human glioma tissues or cell lines compared with normal brain tissue or NHA. Moreover, TP53TG1 and some tumor glucose metabolism related genes, such as GRP78, LDHA, and IDH1 were up-regulated significantly in U87 and LN18 cells under glucose deprivation. In addition, knockdown of TP53TG1 decreased cell proliferation and migration and down-regulated GRP78 and IDH1 expression levels and up-regulated PKM2 levels in U87 cells under glucose deprivation. However, over-expression of TP53TG1 showed the opposite tendency. Moreover, the effects of TP53TG1 were more remarkable in low glucose than that in high glucose. Our data showed that TP53TG1 under glucose deprivation may promote cell proliferation and migration by influencing the expression of glucose metabolism related genes in glioma. J. Cell. Biochem. 118: 4897-4904, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Comparison of Six Automated Treponema-Specific Antibody Assays.

PubMed

Park, Borae G; Yoon, Jihoon G; Rim, John Hoon; Lee, Anna; Kim, Hyon-Suk

2016-01-01

Six different Treponema (TP)-specific immunoassays were compared to the fluorescent treponemal antibody absorption (FTA-ABS) test. A total of 615 samples were tested. The overall percent agreement, analytical sensitivity, and analytical specificity of each assay compared to the FTA-ABS test were as follows: Architect Syphilis TP, 99.2%, 96.8%, and 100%; Cobas Syphilis, 99.8%, 99.4%, and 100%; ADVIA Centaur Syphilis, 99.8%, 99.4%, and 100%; HISCL Anti-TP assay kit, 99.7%, 98.7%, and 100%; Immunoticles Auto3 TP, 99.0%, 97.5%, and 99.6%; Mediace TPLA, 98.0%, 98.1%, and 98.0%. All results that were discrepant between the TP-specific assays were associated with samples from noninfectious cases (11 immunoassay false positives and 7 from previous syphilis cases). Our study demonstrated that TP-specific immunoassays generally showed high sensitivities, specificities, and percentages of agreement compared to FTA-ABS, with rare cases of false-positive or false-negative results. Therefore, most TP-specific immunoassays are acceptable for use in screening for syphilis. However, it is important to perform a thorough review of a patient's clinical and treatment history for interpreting the results of syphilis serology. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

TP53 supports basal-like differentiation of mammary epithelial cells by preventing translocation of deltaNp63 into nucleoli

PubMed Central

Munne, Pauliina M.; Gu, Yuexi; Tumiati, Manuela; Gao, Ping; Koopal, Sonja; Uusivirta, Sanna; Sawicki, Janet; Wei, Gong-Hong; Kuznetsov, Sergey G.

2014-01-01

Multiple observations suggest a cell type-specific role for TP53 in mammary epithelia. We developed an in vitro assay, in which primary mouse mammary epithelial cells (mMECs) progressed from lumenal to basal-like phenotypes based on expression of Krt18 or ΔNp63, respectively. Such transition was markedly delayed in Trp53−/− mMECs suggesting that Trp53 is required for specification of the basal, but not lumenal cells. Evidence from human basal-like cell lines suggests that TP53 may support the activity of ΔNp63 by preventing its translocation from nucleoplasm into nucleoli. In human lumenal cells, activation of TP53 by inhibiting MDM2 or BRCA1 restored the nucleoplasmic expression of ΔNp63. Trp53−/− mMECs eventually lost epithelial features resulting in upregulation of MDM2 and translocation of ΔNp63 into nucleoli. We propose that TP63 may contribute to TP53-mediated oncogenic transformation of epithelial cells and shed light on tissue- and cell type-specific biases observed for TP53-related cancers. PMID:24722541

Mechanism of non-appearance of hiatus in Tibetan Plateau.

PubMed

Ma, Jieru; Guan, Xiaodan; Guo, Ruixia; Gan, Zewen; Xie, Yongkun

2017-06-30

In the recent decade, hiatus is the hottest issue in the community of climate change. As the area of great importance, the Tibetan Plateau (TP), however, did not appear to have any warming stoppage in the hiatus period. In fact, the TP showed a continuous warming in the recent decade. To explore why the TP did not show hiatus, we divide the surface air temperature into dynamically-induced temperature (DIT) and radiatively-forced temperature (RFT) by applying the dynamical adjustment method. Our results show that DIT displayed a relatively uniform warming background in the TP, with no obvious correlations with dynamic factors. Meanwhile, as the major contribution to warming, the RFT effect over the TP played the dominant role. The warming role is illustrated using the temperature change between perturbed and control simulation responses to CO 2 or black carbon (BC) forcing via Community Earth System Model (CESM). It shows that an obvious warming in the TP is induced by the CO 2 warming effect, and BC exhibits an amplifying effect on the warming. Therefore, the continuous warming in the TP was a result of uniform DIT warming over a large scale and enhanced RFT warming at a regional scale.

Tea polyphenols inactivate Cronobacter sakazakii isolated from powdered infant formula.

PubMed

Li, R; Fei, P; Man, C X; Lou, B B; Niu, J T; Feng, J; Sun, L H; Li, M Y; Jiang, Y J

2016-02-01

This study evaluated the antimicrobial activity of tea polyphenols (TP) against 4 Cronobacter sakazakii strains with different sequence types (ST) isolated from powdered infant formula (PIF). The results showed that in normal saline, 5mg/mL of TP (pH 3.44) could eliminate approximately 7.0 log cfu/mL of C. sakazakii within 1 h; in rehydrated PIF, after acidification with HCl (pH 3.55), TP showed a stronger antibacterial activity compared with the controls (malic acid, ascorbic acid, and citric acid). Further, some differences were obvious in tolerance to TP between C. sakazakii strains with different ST. The tolerance of C. sakazakii CE1 (ST4) to TP was found to be greater than that of the other 3 C. sakazakii strains (ST1, ST8, and ST64). The results of recovered test and transmission electron microscope analysis revealed that the action of TP against C. sakazakii was an irreversible bactericidal process caused by leakage of cytoplasm. Taken together, these results indicated that TP had an effective bactericidal effect against C. sakazakii, and provided a new idea for preventing and inactivating C. sakazakii in PIF. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Estimates of diffuse phosphorus sources in surface waters of the United States using a spatially referenced watershed model

USGS Publications Warehouse

Alexander, R.B.; Smith, R.A.; Schwarz, G.E.

2004-01-01

The statistical watershed model SPARROW (SPAtially Referenced Regression On Watershed attributes) was used to estimate the sources and transport of total phosphorus (TP) in surface waters of the United States. We calibrated the model using stream measurements of TP from 336 watersheds of mixed land use and spatial data on topography, soils, stream hydrography, and land use (agriculture, forest, shrub/grass, urban). The model explained 87% of the spatial variability in log transformed stream TP flux (kg yr-1). Predictions of stream yield (kg ha-1 yr-1) were typically within 45% of the observed values at the monitoring sites. The model identified appreciable effects of soils, streams, and reservoirs on TP transport, The estimated aquatic rates of phosphorus removal declined with increasing stream size and rates of water flushing in reservoirs (i.e. areal hydraulic loads). A phosphorus budget for the 2.9 million km2 Mississippi River Basin provides a detailed accounting of TP delivery to streams, the removal of TP in surface waters, and the stream export of TP from major interior watersheds for sources associated with each land-use type. ?? US Government 2004.

Dentin bonding performance and interface observation of an MMA-based restorative material.

PubMed

Shinagawa, Junichi; Inoue, Go; Nikaido, Toru; Ikeda, Masaomi; Sadr, Alireza; Tagami, Junji

2016-07-30

The purpose of this study was to evaluate bonding performance and dentin interface acid resistance using a 4-META/MMA-TBB based restorative material (BF) compared to a conventional 4-META/MMA-TBB resin cement (SB), and the effect of sodium fluoride (NaF) addition to the materials. Dentin surfaces were treated with 10% citric acid-3% ferric chloride (10-3) or 4-META containing self-etching primer (TP), followed by application of BF or SB polymer powders with or without NaF, to evaluate microtensile bond strength (µTBS) in six experimental groups; 10-3/SB, 10-3/BF, TP/SB, TP/BF, TP/SB/NaF and TP/BF/NaF. SEM observation of the resin-dentin interface was performed after acid-base challenge to evaluate interfacial dentin resistance to acid attack. TP/BF showed highest µTBS, while NaF polymers decreased µTBS. TP/BF showed funnel-shaped erosion at the interface, however, NaF polymers improved acid resistance of interface. In conclusion, BF demonstrated high µTBSs and low acid-resistance at the interface. NaF addition enhanced acid resistance but decreased µTBS.

Epigenetic inactivation of the p53-induced long noncoding RNA TP53 target 1 in human cancer

PubMed Central

Diaz-Lagares, Angel; Crujeiras, Ana B.; Lopez-Serra, Paula; Soler, Marta; Setien, Fernando; Goyal, Ashish; Sandoval, Juan; Hashimoto, Yutaka; Martinez-Cardús, Anna; Gomez, Antonio; Heyn, Holger; Moutinho, Catia; Espada, Jesús; Vidal, August; Paúles, Maria; Galán, Maica; Sala, Núria; Akiyama, Yoshimitsu; Martínez-Iniesta, María; Farré, Lourdes; Villanueva, Alberto; Gross, Matthias; Diederichs, Sven; Guil, Sonia; Esteller, Manel

2016-01-01

Long noncoding RNAs (lncRNAs) are important regulators of cellular homeostasis. However, their contribution to the cancer phenotype still needs to be established. Herein, we have identified a p53-induced lncRNA, TP53TG1, that undergoes cancer-specific promoter hypermethylation-associated silencing. In vitro and in vivo assays identify a tumor-suppressor activity for TP53TG1 and a role in the p53 response to DNA damage. Importantly, we show that TP53TG1 binds to the multifaceted DNA/RNA binding protein YBX1 to prevent its nuclear localization and thus the YBX1-mediated activation of oncogenes. TP53TG1 epigenetic inactivation in cancer cells releases the transcriptional repression of YBX1-targeted growth-promoting genes and creates a chemoresistant tumor. TP53TG1 hypermethylation in primary tumors is shown to be associated with poor outcome. The epigenetic loss of TP53TG1 therefore represents an altered event in an lncRNA that is linked to classical tumoral pathways, such as p53 signaling, but is also connected to regulatory networks of the cancer cell. PMID:27821766

Comparison of the inhibitory effects of cilostazol, acetylsalicylic acid and ticlopidine on platelet functions ex vivo. Randomized, double-blind cross-over study.

PubMed

Ikeda, Y; Kikuchi, M; Murakami, H; Satoh, K; Murata, M; Watanabe, K; Ando, Y

1987-05-01

A randomized double-blind cross-over study was conducted to determine the inhibitory effects of acetylsalicylic acid (ASA), ticlopidine (TP) and cilostazol (OPC-13013; in the following briefly called CS), a new antithrombotic agent on platelet functions ex vivo. Nine patients with cerebral thrombosis were enrolled in this study. Patients were given each of the three drugs for one week in a complete cross-over design according to a randomization schedule, followed by a wash-out period with a placebo for one week. It was found that CS and TP significantly inhibited platelet aggregation induced by ADP. Collagen- and arachidonic acid-induced platelet aggregation was all inhibited by CS, TP and ASA. Duncan's multiple range test to compare the anti-platelet effects of the three drugs revealed that: CS greater than ASA and TP greater than ASA in inhibiting ADP-induced platelet aggregation and CS greater than TP and ASA greater than TP in inhibiting arachidonic acid-induced platelet aggregation. These results may suggest that CS is superior to ASA and TP in inhibiting platelet aggregation ex vivo.

MID TERM RESULTS AFTER OPEN HEART SURGERY IN HEMODIALYSIS PATIENTS AWAITING KIDNEY TRANSPLANT: DOES CARDIOVASCULAR SURGICAL INTERVENTION PRIOR TO TRANSPLANTATION PROLONG SURVIVAL?

PubMed

Ozbek, C; Sever, K; Demirhan, O; Mansuroglu, D; Kurtoglu, N; Ugurlucan, M; Sevmis, S; Karakayali, H

2015-12-01

The aim of this study was to compare the mid and long term postoperative outcomes between the hemodialysis-dependent patients awaiting kidney transplantat who underwent open heart surgery in our department during the last five years, and those who did not receive a renal transplant, to determine the predictors of mortality, and assess the possible contribution of post heart surgery kidney transplantation to survival. The patients were separated into two groups: those who underwent a transplantation after open heart surgery were included in the Tp+ group, and those who did not in the Tp- group Between June 2008 and December 2012, 127 dialysis dependent patients awaiting kidney transplant and who underwent open heart surgery were separated into two groups. Those who underwent transplantation after open heart surgery were determined as Tp+ (n=33), and those who did not as Tp- (n=94). Both groups were compared with respect to preoperative paramaters including age, sex, diabetes mellitus (DM), hypertension (HT), hyperlipidemia (HL), obesity, smoking, chronic obstructive pulmonary disease (COPD), peripheral vascular disease (PVD), left ventricle ejection fraction (EF), Euroscore; operative parameters including cross clamp time, perfusion time, number of grafts, use of internal mammary artery (IMA); postoperative parameters including revision, blood transfusion, ventilation time, use of inotropic agents, length of stay in the intensive care unit and hospital, and follow up findings. Problems encountered during follow up were recorded. Predictors of mortality were determined and the survival was calculated. Among the preoperative parameters, when compared with the Tp- group, the Tp+ group had significantly lower values in mean age, presence of DM, obesity, PVD, and Euroscore levels, and higher EF values. Assessment of postoperative values showed that blood transfusion requirement and length of hospital stay were significantly lower in the Tp+ group compared to the Tp- group, whereas the length of follow up was significantly higher in the Tp+ group. The use of inotropic agents was significantly higher in the Tp- group. A logistic regression analysis was made to determine the factors affecting mortality. Revision (p=0.013), blood transfusion (p=0.017), ventilation time (p=0.019), and length of stay in the intensive care unit (p=0.009) were found as predictors of mortality. Survival rates at years 1, 2 and 3 were 86.1%, 81%, 77.5% in the Tp- group, and 96.0%, 96.3%, 90.4% in the Tp+ group. Median survival rate was 41.35±2.02 in the Tp- group, and 49.64±1.59 in the Tp+ group which was significantly higher compared to the Tp- group (p=0.048). Chronic renal failure is among the perioperative risk factors for patients undergoing open heart surgery. Transplantation is still an important health issue due to insufficiency of available transplant organs. Patients with chronic renal failure are well known to have higher risks for coronary artery disease. A radical solution of the cardiovascular system problems prior to kidney transplantation seems to have a significant contribution to the post transplant survival.

Translations on USSR Science and Technology, Biomedical and Behavioral Sciences, Number 42

DTIC Science & Technology

1978-08-08

highly virulent Pan strain of TE virus, naturally weakened by Tp-21 strain Langat virus, and a highly attenuated variant of the latter, Tp-21-237...attenuated variant of Langat virus, Tp-21-237. The earliest pronounced reaction (within the first 3 days) of B-lymphocytes in response to...injection of Tp-21 strain Langat virus was among animals weigh- ing 6-7 gm. When animals were infected with this strain, the highest PFC indices and a

A quantitative assessment of the contributions of climatic indicators to changes in nutrients and oxygen levels in a shallow reservoir in China

NASA Astrophysics Data System (ADS)

Zhang, Chen; Zhang, Wenna; Liu, Hanan; Gao, Xueping; Huang, Yixuan

2017-06-01

Climate change has an indirect effect on water quality in freshwater ecosystems, but it is difficult to assess the contribution of climate change to the complex system. This study explored to what extent climatic indicators (air temperature, wind speed, and rainfall) influence nutrients and oxygen levels in a shallow reservoir, Yuqiao Reservoir, China. The study comprises three parts—describing the temporal trends of climatic indicators and water quality parameters during the period 1992-2011, analyzing the potential impacts of climate on water quality, and finally developing a quantitative assessment to evaluate how climatic factors govern nutrient levels in the reservoir. Our analyses showed that the reservoir experienced substantial cold periods (1992-2001) followed by a warm period (2002-2011). The results showed that increasing air temperature in spring, autumn, and winter and increasing annual wind speed decrease total phosphorus (TP) concentration in the reservoir in spring, summer, and winter. According to the quantitative assessment, the increase in air temperature in spring and winter had a larger contribution to the decrease in TP concentration (47.2 and 64.1%), compared with the influence from decreased wind speed and rainfall. The field data suggest that nutrients decline due to enhanced uptake by macrophytes in years when spring was warmer and the macrophytes started to grow earlier in the season. The increasing wind speed and air temperature in spring also significantly contribute to the increase in dissolved oxygen concentration. This study helps managers to foresee how potential future climate change might influence water quality in similar lake ecosystems.

Climate Change and Drought Events in the Geochemical Records of the Lacustrine Deposits in the Southeastern Tibetan Plateau

PubMed Central

Shi, Zhengtao; Niu, Jie; Su, Huai

2016-01-01

Lacustrine deposits at the margin of the southeastern Tibetan Plateau (SETP) are sensitive indicators for the evolution of the southwest Asian monsoon (SWAM) during the Quaternary. Thus, they can provide insight into the Quaternary climatic history and their relationship with global climatic changes. The results of the geochemical analysis of the Xiaozhongdian Basin section at the SETP suggest that SiO2 had the highest content of the major elements followed by Al2O3. The order of the abundance of the major elements was generally as follows: SiO2>Al2O3>Fe2O3>CaO>MgO>K2O>TiO2>Na2O>MnO2. The geochemical proxies, such as chemical index of alteration (CIA), the index of compositional variability (ICV) and (CaO+K2O+Na2O)/Al2O3, indicate the weak chemical weathering and the aridification of the margin of the SETP during the Heinrich events. In addition, the aridification of the SETP during the Heinrich events may be closely related to the cold signals transmitted from the high latitudes of the North Atlantic to the TP, and the effect caused the cooling effect to be very strong on the TP as a result of the upper-level westerly jet stream and then reduced the suction action associated with the SWAM, thus accelerating the drying rate of Xiaozhongdian Basin, which was amplifying the degree of drought in Heinrich events. PMID:28033377

Experimental additions of aluminum sulfate and ammonium nitrate to in situ mesocosms to reduce cyanobacterial biovolume and microcystin concentration

USGS Publications Warehouse

Harris, Ted D.; Wilhelm, Frank M.; Graham, Jennifer L.; Loftin, Keith A.

2014-01-01

Recent studies suggest that nitrogen additions to increase the total nitrogen:total phosphorus (TN:TP) ratio may reduce cyanobacterial biovolume and microcystin concentration in reservoirs. In systems where TP is >100 μg/L, however, nitrogen additions to increase the TN:TP ratio could cause ammonia, nitrate, or nitrite toxicity to terrestrial and aquatic organisms. Reducing phosphorus via aluminum sulfate (alum) may be needed prior to nitrogen additions aimed at increasing the TN:TP ratio. We experimentally tested this sequential management approach in large in situ mesocosms (70.7 m3) to examine effects on cyanobacteria and microcystin concentration. Because alum removes nutrients and most seston from the water column, alum treatment reduced both TN and TP, leaving post-treatment TN:TP ratios similar to pre-treatment ratios. Cyanobacterial biovolume was reduced after alum addition, but the percent composition (i.e., relative) cyanobacterial abundance remained unchanged. A single ammonium nitrate (nitrogen) addition increased the TN:TP ratio 7-fold. After the TN:TP ratio was >50 (by weight), cyanobacterial biovolume and abundance were reduced, and chrysophyte and cryptophyte biovolume and abundance increased compared to the alum treatment. Microcystin was not detectable until the TN:TP ratio was <50. Although both treatments reduced cyanobacteria, only the nitrogen treatment seemed to stimulate energy flow from primary producers to zooplankton, which suggests that combining alum and nitrogen treatments may be a viable in-lake management strategy to reduce cyanobacteria and possibly microcystin concentrations in high-phosphorus systems. Additional studies are needed to define best management practices before combined alum and nitrogen additions are implemented as a reservoir management strategy.

Experimental additions of aluminum sulfateand ammonium nitrate to in situ mesocosms toreduce cyanobacterial biovolume and microcystinconcentration

USGS Publications Warehouse

Harris, Theodore D.; Wilhelm, Frank M.; Graham, Jennifer L.; Loftin, Keith A.

2014-01-01

Recent studies suggest that nitrogen additions to increase the total nitrogen:total phosphorus (TN:TP) ratio may reduce cyanobacterial biovolume and microcystin concentration in reservoirs. In systems where TP is >100 μg/L, however, nitrogen additions to increase the TN:TP ratio could cause ammonia, nitrate, or nitrite toxicity to terrestrial and aquatic organisms. Reducing phosphorus via aluminum sulfate (alum) may be needed prior to nitrogen additions aimed at increasing the TN:TP ratio.We experimentally tested this sequential management approach in large in situ mesocosms (70.7 m3) to examine effects on cyanobacteria and microcystin concentration. Because alum removes nutrients and most seston from the water column, alum treatment reduced both TN and TP, leaving post-treatment TN:TP ratios similar to pre-treatment ratios. Cyanobacterial biovolume was reduced after alum addition, but the percent composition (i.e., relative) cyanobacterial abundance remained unchanged. A single ammonium nitrate (nitrogen) addition increased the TN:TP ratio 7-fold. After the TN:TP ratio was >50 (by weight), cyanobacterial biovolume and abundance were reduced, and chrysophyte and cryptophyte biovolume and abundance increased compared to the alum treatment. Microcystin was not detectable until the TN:TP ratio was <50. Although both treatments reduced cyanobacteria, only the nitrogen treatment seemed to stimulate energy flow from primary producers to zooplankton, which suggests that combining alum and nitrogen treatments may be a viable in-lake management strategy to reduce cyanobacteria and possibly microcystin concentrations in high-phosphorus systems. Additional studies are needed to define best management practices before combined alum and nitrogen additions are implemented as a reservoir management strategy.

Total Pancreatectomy and Islet Auto-Transplantation in Children for Chronic Pancreatitis. Indication, Surgical Techniques, Post Operative Management and Long-Term Outcomes

PubMed Central

Chinnakotla, Srinath; Bellin, Melena D.; Schwarzenberg, Sarah J.; Radosevich, David M.; Cook, Marie; Dunn, Ty B.; Beilman, Gregory J.; Freeman, Martin L.; Balamurugan, A.N.; Wilhelm, Josh; Bland, Barbara; Jimenez-Vega, Jose M; Hering, Bernhard J.; Vickers, Selwyn M.; Pruett, Timothy L.; Sutherland, David E.R.

2014-01-01

Objective Describe the surgical technique, complications and long term outcomes of total pancreatectomy and islet auto transplantation (TP-IAT) in a large series of pediatric patients. Summary Background Data Surgical management of childhood pancreatitis is not clear; partial resection or drainage procedures often provide transient pain relief, but long term recurrence is common due to the diffuse involvement of the pancreas. Total pancreatectomy (TP) removes the source of the pain, while islet auto transplantation (IAT) potentially can prevent or minimize TP-related diabetes. Methods Retrospective review of 75 children undergoing TP-IAT for chronic pancreatitis who had failed medical, endoscopic or surgical treatment between 1989–2012. Results Pancreatitis pain and the severity of pain statistically improved in 90% of patients after TP-IAT (p =<0.001). The relief from narcotics was sustained. Of the 75 patients undergoing TP-IAT, 31 (41.3%) achieved insulin independence. Younger age (p=0.032), lack of prior Puestow (p=0.018), lower body surface area (p=0.048), IEQ per Kg Body Weight (p=0.001) and total IEQ (100,000) (0.004) were associated with insulin independence. By multivariate analysis, 3 factors were associated with insulin independence after TP-IAT:(1) male gender, (2) lower body surface area and the (3) higher total IEQ per kilogram body weight. Total IEQ (100,000) was the single factor most strongly associated with insulin independence (OR = 2.62; p value < 0.001). Conclusions TP-IAT provides sustained pain relief and improved quality of life. The β cell function is dependent on islet yield. TP-IAT is an effective therapy for children with painful pancreatitis that fail medical and or endoscopic management PMID:24509206

Robotic total pancreatectomy with or without autologous islet cell transplantation: replication of an open technique through a minimal access approach.

PubMed

Zureikat, Amer H; Nguyen, Trang; Boone, Brian A; Wijkstrom, Martin; Hogg, Melissa E; Humar, Abhinav; Zeh, Herbert

2015-01-01

Total pancreatectomy (TP) is a morbid but sometimes necessary operation. Robotic TP is not often reported but may harbor some advantages compared to the open approach. This manuscript details a single institution's outcomes and technique of robotic TP. An accompanying video demonstrates a robotic TP with auto islet cell transplantation (IAT) in which (1) the arterial blood supply and venous drainage are kept intact until the last step of the TP to minimize warm ischemia time and (2) extirpation of the entire pancreas is performed without dividing the pancreatic neck to maximize islet recovery. This study is a retrospective review of a prospective database of perioperative outcomes of all consecutive robotic TPs at a single institution. This included a single robotic TP with IAT performed on a twenty-year-old patient with chronic pancreatitis. Between 2010 and January 2014, ten robotic TPs were performed (7 males, mean age 58 years), one of which included an IAT. Median body mass index was 28. Indications were intraductal papillary mucinous neoplasms (6), pancreatic adenocarcinoma (1), and chronic pancreatitis (3). The median operative time was 560 min with a median estimated blood loss of 650 ml. One case was converted to laparotomy. Ninety days mortality and Clavien III-IV complication rate were 0 and 20 %, respectively. The average length of stay was 10 ± 3 days, with only 1 readmission within 90 days. The single TP and IAT were completed successfully without conversion, and were achieved without division of the pancreatic neck thereby maintaining vascular inflow to an entire specimen up until extraction. This represents the largest series of robotic TP, demonstrating its safety and feasibility. Additionally, TP and IAT using the technique described above can be recapitulated using the robotic approach.

Estimation of total nitrogen and total phosphorus in streams of the Middle Columbia River Basin (Oregon, Washington, and Idaho) using SPARROW models, with emphasis on the Yakima River Basin, Washington

USGS Publications Warehouse

Johnson, Henry M.; Black, Robert W.; Wise, Daniel R.

2013-01-01

The watershed model SPARROW (Spatially Related Regressions on Watershed attributes) was used to predict total nitrogen (TN) and total phosphorus (TP) loads and yields for the Middle Columbia River Basin in Idaho, Oregon, and Washington. The new models build on recently published models for the entire Pacific Northwest, and provide revised load predictions for the arid interior of the region by restricting the modeling domain and recalibrating the models. Results from the new TN and TP models are provided for the entire region, and discussed with special emphasis on the Yakima River Basin, Washington. In most catchments of the Yakima River Basin, the TN and TP in streams is from natural sources, specifically nitrogen fixation in forests (TN) and weathering and erosion of geologic materials (TP). The natural nutrient sources are overshadowed by anthropogenic sources of TN and TP in highly agricultural and urbanized catchments; downstream of the city of Yakima, most of the load in the Yakima River is derived from anthropogenic sources. Yields of TN and TP from catchments with nearly uniform land use were compared with other yield values and export coefficients published in the scientific literature, and generally were in agreement. The median yield of TN was greatest in catchments dominated by agricultural land and smallest in catchments dominated by grass and scrub land. The median yield of TP was greatest in catchments dominated by forest land, but the largest yields (90th percentile) of TP were from agricultural catchments. As with TN, the smallest TP yields were from catchments dominated by grass and scrub land.

Somatic and Germline TP53 Alterations in Second Malignant Neoplasms from Pediatric Cancer Survivors.

PubMed

Sherborne, Amy L; Lavergne, Vincent; Yu, Katharine; Lee, Leah; Davidson, Philip R; Mazor, Tali; Smirnoff, Ivan V; Horvai, Andrew E; Loh, Mignon; DuBois, Steven G; Goldsby, Robert E; Neglia, Joseph P; Hammond, Sue; Robison, Leslie L; Wustrack, Rosanna; Costello, Joseph F; Nakamura, Alice O; Shannon, Kevin M; Bhatia, Smita; Nakamura, Jean L

2017-04-01

Purpose: Second malignant neoplasms (SMNs) are severe late complications that occur in pediatric cancer survivors exposed to radiotherapy and other genotoxic treatments. To characterize the mutational landscape of treatment-induced sarcomas and to identify candidate SMN-predisposing variants, we analyzed germline and SMN samples from pediatric cancer survivors. Experimental Design: We performed whole-exome sequencing (WES) and RNA sequencing on radiation-induced sarcomas arising from two pediatric cancer survivors. To assess the frequency of germline TP53 variants in SMNs, Sanger sequencing was performed to analyze germline TP53 in 37 pediatric cancer survivors from the Childhood Cancer Survivor Study (CCSS) without any history of a familial cancer predisposition syndrome but known to have developed SMNs. Results: WES revealed TP53 mutations involving p53's DNA-binding domain in both index cases, one of which was also present in the germline. The germline and somatic TP53- mutant variants were enriched in the transcriptomes for both sarcomas. Analysis of TP53- coding exons in germline specimens from the CCSS survivor cohort identified a G215C variant encoding an R72P amino acid substitution in 6 patients and a synonymous SNP A639G in 4 others, resulting in 10 of 37 evaluable patients (27%) harboring a germline TP53 variant. Conclusions: Currently, germline TP53 is not routinely assessed in patients with pediatric cancer. These data support the concept that identifying germline TP53 variants at the time a primary cancer is diagnosed may identify patients at high risk for SMN development, who could benefit from modified therapeutic strategies and/or intensive posttreatment monitoring. Clin Cancer Res; 23(7); 1852-61. ©2016 AACR . ©2016 American Association for Cancer Research.

Somatic and germline TP53 alterations in second malignant neoplasms from pediatric cancer survivors

PubMed Central

Sherborne, Amy L.; Lavergne, Vincent; Yu, Katharine; Lee, Leah; Davidson, Philip R.; Mazor, Tali; Smirnoff, Ivan; Horvai, Andrew; Loh, Mignon; DuBois, Steven G.; Goldsby, Robert E.; Neglia, Joseph; Hammond, Sue; Robison, Leslie L.; Wustrack, Rosanna; Costello, Joseph; Nakamura, Alice O.; Shannon, Kevin; Bhatia, Smita; Nakamura, Jean L.

2016-01-01

Purpose Second malignant neoplasms (SMNs) are severe late complications that occur in pediatric cancer survivors exposed to radiotherapy and other genotoxic treatments. To characterize the mutational landscape of treatment-induced sarcomas and to identify candidate SMN-predisposing variants we analyzed germline and SMN samples from pediatric cancer survivors. Experimental Design We performed whole exome sequencing (WES) and RNA sequencing on radiation-induced sarcomas arising from two pediatric cancer survivors. To assess the frequency of germline TP53 variants in SMNs, Sanger sequencing was performed to analyze germline TP53 in thirty-seven pediatric cancer survivors from the Childhood Cancer Survivor Study (CCSS) without history of a familial cancer predisposition syndrome but known to have developed SMNs. Results WES revealed TP53 mutations involving p53’s DNA binding domain in both index cases, one of which was also present in the germline. The germline and somatic TP53 mutant variants were enriched in the transcriptomes for both sarcomas. Analysis of TP53 coding exons in germline specimens from the CCSS survivor cohort identified a G215C variant encoding an R72P amino acid substitution in six patients and a synonymous single nucleotide polymorphism A639G in four others, resulting in ten out of 37 evaluable patients (27%) harboring a germline TP53 variant. Conclusions Currently, germline TP53 is not routinely assessed in pediatric cancer patients. These data support the concept that identifying germline TP53 variants at the time a primary cancer is diagnosed may identify patients at high risk for SMN development, who could benefit from modified therapeutic strategies and/or intensive post-treatment monitoring. PMID:27683180

Scenario analysis of the impacts of socioeconomic development on phosphorous export and loading from the Dongting Lake watershed, China.

PubMed

Hou, Ying; Chen, Weiping; Liao, Yuehua; Luo, Yueping

2017-12-01

Socioeconomic development in lake watersheds is closely related with lake nutrient pollution. As the second largest freshwater lake in China, the Dongting Lake has been experiencing an increase in nutrient loading and a growing risk of eutrophication. This study aimed to reveal the likely impacts of the socioeconomic development of the Dongting Lake watershed on the phosphorous pollution in the lake. We estimated the contributions from different sources and sub-watersheds to the total phosphorous (TP) export and loading from the Dongting Lake watershed under two most likely socioeconomic development scenarios. Moreover, we predicted the likely permissible and actual TP loadings to the Dongting Lake. Under both two scenarios, three secondary sub-watersheds-the upper and lower reaches of the Xiang River watershed and the Dongting Lake Area-are expected to dominate the contribution to the TP export from the Dongting Lake watershed in 2020. Three primary sub-watersheds-the Dongting Lake Area, the Xiang River, and the Yuan River watersheds-are predicted to be the major contributors to the TP loading from the entire watershed. The two scenarios are expected to have a slight difference in TP export and lake TP loading. Livestock husbandry is expected to be the predominant anthropogenic TP source in each of the sub-watersheds under both scenarios. Compared to 2010, permissible TP loading is not expected to increase but actual TP loading is predicted to grow significantly in 2020. Our study provides methodologies to identify the key sources and regions of lake nutrient loading from watersheds with complex socioeconomic context, and to reveal the potential influences of socioeconomic development on nutrient pollution in lake watersheds.

Development of a Novel Tetravalent Synthetic Peptide That Binds to Phosphatidic Acid.

PubMed

Ogawa, Rina; Nagao, Kohjiro; Taniuchi, Kentaro; Tsuchiya, Masaki; Kato, Utako; Hara, Yuji; Inaba, Takehiko; Kobayashi, Toshihide; Sasaki, Yoshihiro; Akiyoshi, Kazunari; Watanabe-Takahashi, Miho; Nishikawa, Kiyotaka; Umeda, Masato

2015-01-01

We employed a multivalent peptide-library screening technique to identify a peptide motif that binds to phosphatidic acid (PA), but not to other phospholipids such as phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS). A tetravalent peptide with the sequence motif of MARWHRHHH, designated as PAB-TP (phosphatidic acid-binding tetravalent peptide), was shown to bind as low as 1 mol% of PA in the bilayer membrane composed of PC and cholesterol. Kinetic analysis of the interaction between PAB-TP and the membranes containing 10 mol% of PA showed that PAB-TP associated with PA with a low dissociation constant of KD = 38 ± 5 nM. Coexistence of cholesterol or PE with PA in the membrane enhanced the PAB-TP binding to PA by increasing the ionization of the phosphomonoester head group as well as by changing the microenvironment of PA molecules in the membrane. Amino acid replacement analysis demonstrated that the tryptophan residue at position 4 of PAB-TP was involved in the interaction with PA. Furthermore, a series of amino acid substitutions at positions 5 to 9 of PAB-TP revealed the involvement of consecutive histidine and arginine residues in recognition of the phosphomonoester head group of PA. Our results demonstrate that the recognition of PA by PAB-TP is achieved by a combination of hydrophobic, electrostatic and hydrogen-bond interactions, and that the tetravalent structure of PAB-TP contributes to the high affinity binding to PA in the membrane. The novel PA-binding tetravalent peptide PAB-TP will provide insight into the molecular mechanism underlying the recognition of PA by PA-binding proteins that are involved in various cellular events.

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

Simoes, Maria L.; Hockley, Sarah L.; Schwerdtle, Tanja

Aristolochic acid (AA) is the causative agent of urothelial tumours associated with aristolochic acid nephropathy. These tumours contain TP53 mutations and over-express TP53. We compared transcriptional and translational responses of two isogenic HCT116 cell lines, one expressing TP53 (p53-WT) and the other with this gene knocked out (p53-null), to treatment with aristolochic acid I (AAI) (50-100 {mu}M) for 6-48 h. Modulation of 118 genes was observed in p53-WT cells and 123 genes in p53-null cells. Some genes, including INSIG1, EGR1, CAV1, LCN2 and CCNG1, were differentially expressed in the two cell lines. CDKN1A was selectively up-regulated in p53-WT cells, leadingmore » to accumulation of TP53 and CDKN1A. Apoptotic signalling, measured by caspase-3 and -7 activity, was TP53-dependent. Both cell types accumulated in S phase, suggesting that AAI-DNA adducts interfere with DNA replication, independently of TP53 status. The oncogene MYC, frequently over-expressed in urothelial tumours, was up-regulated by AAI, whereas FOS was down-regulated. Observed modulation of genes involved in endocytosis, e.g. RAB5A, may be relevant to the known inhibition of receptor-mediated endocytosis, an early sign of AA-mediated proximal tubule injury. AAI-DNA adduct formation was significantly greater in p53-WT cells than in p53-null cells. Collectively, phenotypic anchoring of the AAI-induced expression profiles to DNA adduct formation, cell-cycle parameters, TP53 expression and apoptosis identified several genes linked to these biological outcomes, some of which are TP53-dependent. These results strengthen the importance of TP53 in AA-induced cancer, and indicate that other alterations, e.g. to MYC oncogenic pathways, may also contribute.« less

TP53 mutations in myelodysplastic syndrome are strongly correlated with aberrations of chromosome 5, and correlate with adverse prognosis.

PubMed

Kulasekararaj, Austin G; Smith, Alexander E; Mian, Syed A; Mohamedali, Azim M; Krishnamurthy, Pramila; Lea, Nicholas C; Gäken, Joop; Pennaneach, Coralie; Ireland, Robin; Czepulkowski, Barbara; Pomplun, Sabine; Marsh, Judith C; Mufti, Ghulam J

2013-03-01

This study aimed to determine the incidence/prognostic impact of TP53 mutation in 318 myelodysplastic syndrome (MDS) patients, and to correlate the changes to cytogenetics, single nucleotide polymorphism array karyotyping and clinical outcome. The median age was 65 years (17-89 years) and median follow-up was 45 months [95% confidence interval (CI) 27-62 months]. TP53 mutations occurred in 30 (9.4%) patients, exclusively in isolated del5q (19%) and complex karyotype (CK) with -5/5q-(72%), correlated with International Prognostic Scoring System intermediate-2/high, TP53 protein expression, higher blast count and leukaemic progression. Patients with mutant TP53 had a paucity of mutations in other genes implicated in myeloid malignancies. Median overall survival of patients with TP53 mutation was shorter than wild-type (9 versus 66 months, P < 0.001) and it retained significance in multivariable model (Hazard Ratio 3.8, 95%CI 2.3-6.3,P < 0.001). None of the sequentially analysed samples showed a disappearance of the mutant clone or emergence of new clones, suggesting an early occurrence of TP53 mutations. A reduction in mutant clone correlated with response to 5-azacitidine, however clones increased in non-responders and persisted at relapse. The adverse impact of TP53 persists after adjustment for cytogenetic risk and is of practical importance in evaluating prognosis. The relatively common occurrence of these mutations in two different prognostic spectrums of MDS, i.e. isolated 5q- and CK with -5/5q-, possibly implies two different mechanistic roles for TP53 protein. © 2013 Crown copyright. This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.

Role of thioproline on seed germination: interaction ROS-ABA and effects on antioxidative metabolism.

PubMed

Barba-Espin, Gregorio; Nicolas, Eduardo; Almansa, Maria Soledad; Cantero-Navarro, Elena; Albacete, Alfonso; Hernández, José Antonio; Díaz-Vivancos, Pedro

2012-10-01

In this work we investigate the effect of the imbibition of pea seeds with different thioproline (TP) concentrations on the germination percentage and the early growth of the seedlings. The interaction between TP and hydrogen peroxide (H₂O₂) treatments is also analysed in order to test if any synergy in germination and growth occurs. Although the imbibition of pea seeds in the presence of TP did not significantly improve the germination percentage, TP and/or H₂O₂ pre-treatments increased seedlings growth. This increase in seedling growth was reduced by abscisic acid (ABA) addition. Imbibition of pea seeds in the presence of ABA also reduced the endogenous H₂O₂ contents of pea seedlings in control and TP-treated seeds. The incubation of pea seeds with TP and/or H₂O₂ in presence or absence of ABA decreased the activity of H₂O₂-scavenging enzymes. The increase of the endogenous H₂O₂ contents observed in TP and/or H₂O₂ treatments in absence of ABA could be correlated with the decrease in these activities. Finally, the hormone profile of pea seedlings was investigated. The results show that the increase in seedling growth is correlated with a decrease in ABA in samples pre-treated with H₂O₂ and TP + H₂O₂. Nevertheless, no significant differences in endogenous ABA concentration were observed with the TP pre-treatment. This paper suggests a relationship between endogenous H₂O₂ contents and plant growth, so reinforcing the intricate crosstalk between reactive oxygen species (ROS) and plant hormones in seed germination signalling and early seedling development. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

TP53 mutation-correlated genes predict the risk of tumor relapse and identify MPS1 as a potential therapeutic kinase in TP53-mutated breast cancers.

PubMed

Győrffy, Balázs; Bottai, Giulia; Lehmann-Che, Jacqueline; Kéri, György; Orfi, László; Iwamoto, Takayuki; Desmedt, Christine; Bianchini, Giampaolo; Turner, Nicholas C; de Thè, Hugues; André, Fabrice; Sotiriou, Christos; Hortobagyi, Gabriel N; Di Leo, Angelo; Pusztai, Lajos; Santarpia, Libero

2014-05-01

Breast cancers (BC) carry a complex set of gene mutations that can influence their gene expression and clinical behavior. We aimed to identify genes driven by the TP53 mutation status and assess their clinical relevance in estrogen receptor (ER)-positive and ER-negative BC, and their potential as targets for patients with TP53 mutated tumors. Separate ROC analyses of each gene expression according to TP53 mutation status were performed. The prognostic value of genes with the highest AUC were assessed in a large dataset of untreated, and neoadjuvant chemotherapy treated patients. The mitotic checkpoint gene MPS1 was the most significant gene correlated with TP53 status, and the most significant prognostic marker in all ER-positive BC datasets. MPS1 retained its prognostic value independently from the type of treatment administered. The biological functions of MPS1 were investigated in different BC cell lines. We also assessed the effects of a potent small molecule inhibitor of MPS1, SP600125, alone and in combination with chemotherapy. Consistent with the gene expression profiling and siRNA assays, the inhibition of MPS1 by SP600125 led to a reduction in cell viability and a significant increase in cell death, selectively in TP53-mutated BC cells. Furthermore, the chemical inhibition of MPS1 sensitized BC cells to conventional chemotherapy, particularly taxanes. Our results collectively demonstrate that TP53-correlated kinase MPS1, is a potential therapeutic target in BC patients with TP53 mutated tumors, and that SP600125 warrant further development in future clinical trials. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Correlation of MET gene amplification and TP53 mutation with PD-L1 expression in non-small cell lung cancer

PubMed Central

Albitar, Maher; Sudarsanam, Sucha; Ma, Wanlong; Jiang, Shiping; Chen, Wayne; Funari, Vincent; Blocker, Forrest; Agersborg, Sally

2018-01-01

Background The role of MET amplification in lung cancer, particularly in relation to checkpoint inhibition and EGFR WT, has not been fully explored. In this study, we correlated PD-L1 expression with MET amplification and EGFR, KRAS, or TP53 mutation in primary lung cancer. Methods In this retrospective study, tissue collected from 471 various tumors, including 397 lung cancers, was tested for MET amplification by FISH with a MET/centromere probe. PD-L1 expression was evaluated using clone SP142 and standard immunohistochemistry, and TP53, KRAS, and EGFR mutations were tested using next generation sequencing. Results Our results revealed that PD-L1 expression in non-small cell lung cancer is inversely correlated with EGFR mutation (P=0.0003), and positively correlated with TP53 mutation (P=0.0001) and MET amplification (P=0.004). Patients with TP53 mutations had significantly higher MET amplification (P=0.007), and were more likely (P=0.0002) to be EGFR wild type. There was no correlation between KRAS mutation and overall PD-L1 expression, but significant positive correlation between PD-L1 expression and KRAS with TP53 co-mutation (P=0.0002). A cut-off for the ratio of MET: centromere signal was determined as 1.5%, and 4% of lung cancer patients were identified as MET amplified. Conclusions This data suggests that in lung cancer both MET and TP53 play direct roles in regulating PD-L1 opposing EGFR. Moreover, KRAS and TP53 co-mutation may cooperate to drive PD-L1 expression in lung cancer. Adding MET or TP53 inhibitors to checkpoint inhibitors may be an attractive combination therapy in patients with lung cancer and MET amplification. PMID:29568386

Nitrogen and phosphorus flux from the production of Nile tilapia through the application of environmental indicators.

PubMed

Osti, J A S; Moraes, M A B; Carmo, C F; Mercante, C T J

2018-02-01

We aimed in this study utilize environmental indicators as a quantitative method to evaluate and discuss the nitrogen (TN) and phosphorus (TP) flux by a production stage grow-out (termination) of Nile tilapia (Oreochromis niloticus) in fishpond. The TN and TP load, the mass balance, the input of TN and TP via feed and the converted nutrients in fish biomass are the environmental indicators applied in this study. During the production cycle (128 days), the system exported 15,931 g TN and 4,189 g TP that were related to the amount of feed supplied (r Pearson = 0.8825 and r = 0.8523, respectively), corroborated by the feed conversion ratio (1.61:1). The indicators showed that 26% TN and 45% TP were reversed into fish biomass, 62% TN and 40% TP were retained in the fishpond, and 12% TN and 15% TP were exported via effluent. The largest contribution of nutrients generated by the system and exported via effluent was observed in phase III and IV. This result is supported by the feed conversion ratio 2.14 and 2.21:1 obtained at this phase, a fact explained by the amount of feed offered and the fish metabolism. Application of environmental indicators showed to be an efficient tool to quantify flux of TN and TP produced during the grow-out period of Nile tilapia and therefore, guide management practices more sustainable. Concerning the environmental sustainability of the activity the implementation of best management practices such as the better control of the feed amount offered would lead to a smaller loss of TN and TP to the water. Furthermore, the use of better quality feeds would allow greater nutrient assimilation efficiency.

Chrysophanic acid reduces testosterone-induced benign prostatic hyperplasia in rats by suppressing 5α-reductase and extracellular signal-regulated kinase

PubMed Central

Kim, Hye-Lin; Jung, Yunu; Kang, JongWook; Jeong, Mi-Young; Sethi, Gautam; Ahn, Kwang Seok; Um, Jae-Young

2017-01-01

Benign prostatic hyperplasia (BPH) is one of the most common chronic diseases in male population, of which incidence increases gradually with age. In this study, we investigated the effect of chrysophanic acid (CA) on BPH. BPH was induced by a 4-week injection of testosterone propionate (TP). Four weeks of further injection with vehicle, TP, TP + CA, TP + finasteride was carried on. In the CA treatment group, the prostate weight was reduced and the TP-induced histological changes were restored as the normal control group. CA treatment suppressed the TP-elevated prostate specific antigen (PSA) expression. In addition, 5α-reductase, a crucial factor in BPH development, was suppressed to the normal level close to the control group by CA treatment. The elevated expressions of androgen receptor (AR), estrogen receptor α and steroid receptor coactivator 1 by TP administration were also inhibited in the CA group when compared to the TP-induced BPH group. Then we evaluated the changes in three major factors of the mitogen-activated protein kinase chain during prostatic hyperplasia; extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38). While ERK was elevated in the process of BPH, JNK and p38 was not changed. This up-regulated ERK was also reduced as normal by CA treatment. Further in vitro studies with RWPE-1 cells confirmed TP-induced proliferation and elevated AR, PSA and p-ERK were all reduced by CA treatment. Overall, these results suggest a potential pharmaceutical feature of CA in the treatment of BPH. PMID:27880726

Good Days, Bad Days: Wind as a Driver of Foraging Success in a Flightless Seabird, the Southern Rockhopper Penguin

PubMed Central

Dehnhard, Nina; Ludynia, Katrin; Poisbleau, Maud; Demongin, Laurent; Quillfeldt, Petra

2013-01-01

Due to their restricted foraging range, flightless seabirds are ideal models to study the short-term variability in foraging success in response to environmentally driven food availability. Wind can be a driver of upwelling and food abundance in marine ecosystems such as the Southern Ocean, where wind regime changes due to global warming may have important ecological consequences. Southern rockhopper penguins (Eudyptes chrysocome) have undergone a dramatic population decline in the past decades, potentially due to changing environmental conditions. We used a weighbridge system to record daily foraging mass gain (the difference in mean mass of adults leaving the colony in the morning and returning to the colony in the evening) of adult penguins during the chick rearing in two breeding seasons. We related the day-to-day variability in foraging mass gain to ocean wind conditions (wind direction and wind speed) and tested for a relationship between wind speed and sea surface temperature anomaly (SSTA). Foraging mass gain was highly variable among days, but did not differ between breeding seasons, chick rearing stages (guard and crèche) and sexes. It was strongly correlated between males and females, indicating synchronous changes among days. There was a significant interaction of wind direction and wind speed on daily foraging mass gain. Foraging mass gain was highest under moderate to strong winds from westerly directions and under weak winds from easterly directions, while decreasing under stronger easterly winds and storm conditions. Ocean wind speed showed a negative correlation with daily SSTA, suggesting that winds particularly from westerly directions might enhance upwelling and consequently the prey availability in the penguins' foraging areas. Our data emphasize the importance of small-scale, wind-induced patterns in prey availability on foraging success, a widely neglected aspect in seabird foraging studies, which might become more important with increasing changes in climatic variability. PMID:24236139

Interannual coherent variability of SSTA and SSHA in the Tropical Indian Ocean

NASA Astrophysics Data System (ADS)

Feng, J. Q.

2012-01-01

Sea surface height derived from the multiple ocean satellite altimeter missions (TOPEX/Poseidon, Jason-1, ERS, Envisat et al.) and sea surface temperature from National Centers for Environmental Prediction (NCEP) over 1993-2008 are analyzed to investigate the coherent patterns between the interannual variability of the sea surface and subsurface in the Tropical Indian Ocean, by jointly adopting Singular Value Decomposition (SVD) and Extended Associate Pattern Analysis (EAPA) methods. Results show that there are two dominant coherent modes with the nearly same main period of about 3-5 yr, accounting for 86 % of the total covariance in all, but 90° phase difference between them. The primary pattern is characterized by a east-west dipole mode associated with the mature phase of ENSO, and the second presents a sandwich mode having one sign anomalies along Sumatra-Java coast and northeast of Madagascar, whilst an opposite sign between the two regions. The robust correlations of the sea surface height anomaly (SSHA) with sea surface temperature anomaly (SSTA) in the leading modes indicate a strong interaction between them, though the highest correlation coefficient appears with a time lag. And there may be some physical significance with respect to ocean dynamics implied in SSHA variability. Analyzing results show that the features of oceanic waves with basin scale, of which the Rossby wave is prominent, are apparent in the dominant modes. It is further demonstrated from the EAPA that the equatorial eastward Kelvin wave and off-equatorial westward Rossby wave as well as their reflection in the east and west boundary, respectively, are important dynamic mechanisms in the evolution of the two leading coherent patterns. Results of the present study suggest that the upper ocean thermal variations on the timescale of interannual coherent with the ocean dynamics in spatial structure and temporal evolution are mainly attributed to the ocean waves.

Prospects for seasonal forecasting of summer drought and low river flow anomalies in England and Wales

NASA Astrophysics Data System (ADS)

Wedgbrow, C. S.; Wilby, R. L.; Fox, H. R.; O'Hare, G.

2002-02-01

Future climate change scenarios suggest enhanced temporal and spatial gradients in water resources across the UK. Provision of seasonal forecast statistics for surface climate variables could alleviate some negative effects of climate change on water resource infrastructure. This paper presents a preliminary investigation of spatial and temporal relationships between large-scale North Atlantic climatic indices, drought severity and river flow anomalies in England and Wales. Potentially useful predictive relationships are explored between winter indices of the Polar-Eurasian (POL) teleconnection pattern, the North Atlantic oscillation (NAO), North Atlantic sea surface temperature anomalies (SSTAs), and the summer Palmer drought severity index (PDSI) and reconstructed river flows in England and Wales. Correlation analyses, coherence testing and an index of forecast potential, demonstrate that preceding winter values of the POL index, SSTA (and to a lesser extent the NAO), provide indications of summer and early autumn drought severity and river flow anomalies in parts of northwest, southwest and southeast England. Correlation analyses demonstrate that positive winter anomalies of T1, POL index and NAO index are associated with negative PDSI (i.e. drought) across eastern parts of the British Isles in summer (r < 0.51). Coherence tests show that a positive winter SSTA (1871-1995) and POL index (1950-95) have preceded below-average summer river flows in the northwest and southwest of England and Wales in 70 to 100% of summers. The same rivers have also experienced below-average flows during autumn following negative winter phases of the NAO index in 64 to 93% of summers (1865-1995). Possible explanations for the predictor-predictand relationships are considered, including the memory of groundwater, and ocean-atmosphere coupling, and regional manifestations of synoptic rainfall processes. However, further research is necessary to increase the number of years and predictor variables from which it is possible to derive rules that may be useful for forecasting.

Highly Efficient White Organic Light Emitting Diodes Using New Blue Fluorescence Emitter.

PubMed

Kim, Seungho; Kim, Beomjin; Lee, Jaehyun; Yu, Young-Jun; Park, Jongwook

2015-07-01

Two different emitting compounds, 1-[1,1';3',1"]Terphenyl-5'-yl-6-(10-[1,1';3',1"]terpheny-5'-yl- anthracen-9-yl)-pyrene (TP-AP-TP) and Poly-phenylene vinylene derivative (PDY 132) were used to white OLED device. By incorporating adjacent blue and yellow emitting layers in a multi-layered structure, highly efficient white emission has been attained. The device was fabricated with a hybrid configuration structure: ITO/PEDOT (40 nm)/PDY-132 (8-50 nm)/ NPB (10 nm)/TP-AP-TP (30 nm)/Alq3 (20 nm)/LiF (1 nm)/Al (200 nm). After fixing TP-AP-TP thickness of 30 nm by evaporation, PDY-132 thickness varied with 8, 15, 35, and 50 nm by spin coating in device. The luminance efficiency of the white devices at 10 mA/cm2 were 2.93 cd/A-6.55 cd/A. One of white devices showed 6.55 cd/A and white color of (0.290, 0.331).

Time to get healthy: associations of time perspective with perceived health status and health behaviors.

PubMed

Griva, Fay; Tseferidi, Sofia-Ioanna; Anagnostopoulos, Fotios

2015-01-01

The present study examined the associations of time perspective (TP) with health behaviors including smoking, exercise, and body mass index (BMI), and perceptions of health status after controlling for sociodemographic factors. Participants (N = 413) completed a web-based questionnaire that included a short version of the Zimbardo Time Perspective Inventory, and reported their weight, height, smoking, and exercise frequency. Future TP was associated with more physical exercise, whereas past-negative and present-fatalistic dimensions were associated with higher BMI. Smoking was not associated with any of the TP dimensions. Additionally, all of the dimensions of TP were found to be associated with conceptually relevant perceptions of health status. Research on TP predominantly focuses on the future and the present orientation, but the findings of the present study suggest that all dimensions of TP should be used in health-related research. Also, issues regarding the role of the present-hedonistic dimension are discussed and directions for future research are proposed.

Dioxygen activation by non-adiabatic oxidative addition to a single metal center [O 2 activation by non-adiabatic oxidative addition to a single metal center

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

Akturk, Eser S.; Yap, Glenn P. A.; Theopold, Klaus H.

2015-10-16

A chromium(I) dinitrogen complex reacts rapidly with O 2 to form the mononuclear dioxo complex [Tp tBu,MeCr V(O) 2] (Tp tBu,Me=hydrotris(3- tert-butyl-5-methylpyrazolyl)borate), whereas the analogous reaction with sulfur stops at the persulfido complex [Tp tBu,MeCr III(S 2)]. The transformation of the putative peroxo intermediate [Tp tBu,MeCr III(O 2)] (S= 3/ 2) into [Tp tBu,MeCr V(O) 2] (S= 1/ 2) is spin-forbidden. The minimum-energy crossing point for the two potential energy surfaces has been identified. Finally, although the dinuclear complex [(Tp tBu,MeCr) 2(μ-O) 2] exists, mechanistic experiments suggest that O 2 activation occurs on a single metal center, by an oxidativemore » addition on the quartet surface followed by crossover to the doublet surface.« less

The default mode network and recurrent depression: a neurobiological model of cognitive risk factors.

PubMed

Marchetti, Igor; Koster, Ernst H W; Sonuga-Barke, Edmund J; De Raedt, Rudi

2012-09-01

A neurobiological account of cognitive vulnerability for recurrent depression is presented based on recent developments of resting state neural networks. We propose that alterations in the interplay between task positive (TP) and task negative (TN) elements of the Default Mode Network (DMN) act as a neurobiological risk factor for recurrent depression mediated by cognitive mechanisms. In the framework, depression is characterized by an imbalance between TN-TP components leading to an overpowering of TP by TN activity. The TN-TP imbalance is associated with a dysfunctional internally-focused cognitive style as well as a failure to attenuate TN activity in the transition from rest to task. Thus we propose the TN-TP imbalance as overarching neural mechanism involved in crucial cognitive risk factors for recurrent depression, namely rumination, impaired attentional control, and cognitive reactivity. During remission the TN-TP imbalance persists predisposing to vulnerability of recurrent depression. Empirical data to support this model is reviewed. Finally, we specify how this framework can guide future research efforts.

Moisture increase in response to high-altitude warming evidenced by tree-rings on the southeastern Tibetan Plateau

NASA Astrophysics Data System (ADS)

Li, Jinbao; Shi, Jiangfeng; Zhang, David D.; Yang, Bao; Fang, Keyan; Yue, Pak Hong

2017-01-01

Rapid warming has been observed in the high-altitude areas around the globe, but the implications on moisture change are not fully understood. Here we use tree-rings to reveal common moisture change on the southeastern Tibetan Plateau (TP) during the past five centuries, and show that regional moisture change in late spring to early summer (April-June) is closely related to large-scale temperature anomaly over the TP, with increased moisture coincident with periods of high temperature. The most recent pluvial during the 1990s-2000s is likely the wettest for the past five centuries, which coincides with the warmest period on the TP during the past millennium. Dynamic analysis reveals that vertical air convection is enhanced in response to anomalous TP surface warming, leading to an increase in lower-tropospheric humidity and effective precipitation over the southeastern TP. The coherent warm-wet relationship identified in both tree-rings and dynamic analysis implies a generally wetter condition on the southeastern TP under future warming.

Electron heating and Tp/Te variations during magnetic dipolarizations

NASA Astrophysics Data System (ADS)

Grigorenko, Elena; Kronberg, Elena; Daly, Patrick; Ganushkina, Natalia; Lavraud, Benoit; Sauvaud, Jean-Andre; Zelenyi, Lev

2017-04-01

The proton-to-electron temperature ratio (Tp/Te) in the plasma sheet (PS) of the Earth's magnetotail is studied by using 5 years of Cluster observations (2001-2005). The PS intervals are searched within a region defined with -19

Neuroanatomical correlates of time perspective: A voxel-based morphometry study.

PubMed

Chen, Zhiyi; Guo, Yiqun; Feng, Tingyong

2018-02-26

Previous studies indicated that time perspective can affect many behaviors, such as decisions, risk taking, substance abuse and health behaviors. However, very little is known about the neural substrates of time perspective (TP). To address this question, we characterized different dimensions of TP (including the Past, Present, and Future TP) using standardized Zimbardo Time Perspective Inventory (ZTPI), and quantified the gray matter volume using voxel-based morphometry (VBM) method across two independent samples. Our whole-brain analysis (sample 1, N=150) revealed Past-Negative TP was positively correlated with the GMV of a cluster in LPFC whereas Past-Positive was negatively correlated with the GMV in OFC, and Future TP was negatively correlated with GMV in mPFC. Moreover, two present scales (Present-Hedonistic and Present-Fatalistic TPs) were positively correlated with the GMV of regions in MTG and precuneus, respectively. We further examined the reliability of these correlations between multidimensional TPs and neuroanatomical structures in another independent sample (sample 2, N=58). Results verified our findings that GMV in LPFC could predict Past-Negative TP while GMV in OFC could predict Past-Positive TP, and the GMV in MTG could predict Present-Hedonistic while the GMV in presuneus could predict Present-Fatalistic, as well as the GMV in mPFC could predict Future TP. Thus, our findings suggest that the existence of selective neural basis underlying TPs, and further provide the stable biomarkers for multidimensional TPs. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of future time perspective on delay discounting is mediated by the gray matter volume of vmPFC.

PubMed

Guo, Yiqun; Chen, Zhiyi; Feng, Tingyong

2017-07-28

Although several previous studies have shown that individuals' attitude towards time could affect their intertemporal preference, little is known about the neural basis of the relation between time perspective (TP) and delay discounting. In the present study, we quantified the gray matter (GM) cortical volume using voxel-based morphometry (VBM) methods to investigate the effect of TP on delay discounting (DD) across two independent samples. For group 1 (102 healthy college students; 46 male; 20.40 ± 1.87 years), behavioral results showed that only Future TP was a significant predictor of DD, and higher scores on Future TP were related to lower discounting rates. Whole-brain analysis revealed that steeper discounting correlated with greater GM volume in the ventromedial prefrontal cortex (vmPFC) and ventral part of posterior cingulate cortex (vPCC). Also, GM volume of a cluster in the vmPFC was correlated with Future TP. Interestingly, there was an overlapping region in vmPFC that was correlated with both DD and Future TP. Region-of-interest analysis further indicated that the overlapping region of vmPFC played a partially mediating role in the relation between Future TP and DD in the other independent dataset (Group 2, 36 healthy college students; 14 male; 20.18±1.80 years). Taken together, our results provide a new perspective from neural basis for explaining the relation between DD and future TP. Copyright © 2017 Elsevier Ltd. All rights reserved.

Triptolide disrupts the actin-based Sertoli-germ cells adherens junctions by inhibiting Rho GTPases expression

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

Wang, Xiang; Zhao, Fang

Triptolide (TP), derived from the medicinal plant Triterygium wilfordii Hook. f. (TWHF), is a diterpene triepoxide with variety biological and pharmacological activities. However, TP has been restricted in clinical application due to its narrow therapeutic window especially in reproductive system. During spermatogenesis, Sertoli cell cytoskeleton plays an essential role in facilitating germ cell movement and cell-cell actin-based adherens junctions (AJ). At Sertoli cell-spermatid interface, the anchoring device is a kind of AJ, known as ectoplasmic specializations (ES). In this study, we demonstrate that β-actin, an important component of cytoskeleton, has been significantly down-regulated after TP treatment. TP can inhibit themore » expression of Rho GTPase such as, RhoA, RhoB, Cdc42 and Rac1. Downstream of Rho GTPase, Rho-associated protein kinase (ROCKs) gene expressions were also suppressed by TP. F-actin immunofluorescence proved that TP disrupts Sertoli cells cytoskeleton network. As a result of β-actin down-regulation, TP treatment increased expression of testin, which indicating ES has been disassembled. In summary, this report illustrates that TP induces cytoskeleton dysfunction and disrupts cell-cell adherens junctions via inhibition of Rho GTPases. - Highlights: • Triptolide induced the disruption of Sertoli-germ cell adherens junction. • Rho GTPases expression and actin dynamics have been suppressed by triptolide. • Actin-based adherens junction is a potential antifertility target of triptolide. • Rho-Rock is involved in the regulation of actin dynamics.« less

How the Plant Temperature Links to the Air Temperature in the Desert Plant Artemisia ordosica.

PubMed

Yu, Ming-Han; Ding, Guo-Dong; Gao, Guang-Lei; Sun, Bao-Ping; Zhao, Yuan-Yuan; Wan, Li; Wang, De-Ying; Gui, Zi-Yang

2015-01-01

Plant temperature (Tp) is an important indicator of plant health. To determine the dynamics of plant temperature and self-cooling ability of the plant, we measured Tp in Artemisia ordosica in July, in the Mu Us Desert of Northwest China. Related factors were also monitored to investigate their effects on Tp, including environmental factors, such as air temperature (Ta), relative humidity, wind speed; and physiological factors, such as leaf water potential, sap flow, and water content. The results indicate that: 1) Tp generally changes in conjunction with Ta mainly, and varies with height and among the plant organs. Tp in the young branches is most constant, while it is the most sensitive in the leaves. 2) Correlations between Tp and environmental factors show that Tp is affected mainly by Ta. 3) The self-cooling ability of the plant was effective by midday, with Tp being lower than Ta. 4) Increasing sap flow and leaf water potential showed that transpiration formed part of the mechanism that supported self-cooling. Increased in water conductance and specific heat at midday may be additional factors that contribute to plant cooling ability. Therefore, our results confirmed plant self-cooling ability. The response to high temperatures is regulated by both transpiration speed and an increase in stem water conductance. This study provides quantitative data for plant management in terms of temperature control. Moreover, our findings will assist species selection with taking plant temperature as an index.

Are Three Sheets Enough? Using Toilet Paper to Teach Science and Mathematics

ERIC Educational Resources Information Center

Woolverton, Christopher J.; Woolverton, Lyssa N.

2006-01-01

Toilet paper (TP) composition and physical characteristics were used to model scientific investigations that combined several "National Science Education Standards." Experiments with TP permitted the integration of TP history, societal change resulting from invention, mathematics (including geometry and statistics), germ theory, and personal…

Does Delayed-Time-Point Imaging Improve 18F-FDG-PET in Patients With MALT Lymphoma?

PubMed Central

Mayerhoefer, Marius E.; Giraudo, Chiara; Senn, Daniela; Hartenbach, Markus; Weber, Michael; Rausch, Ivo; Kiesewetter, Barbara; Herold, Christian J.; Hacker, Marcus; Pones, Matthias; Simonitsch-Klupp, Ingrid; Müllauer, Leonhard; Dolak, Werner; Lukas, Julius; Raderer, Markus

2016-01-01

Purpose To determine whether in patients with extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue lymphoma (MALT), delayed–time-point 2-18F-fluoro-2-deoxy-d-glucose-positron emission tomography (18F-FDG-PET) performs better than standard–time-point 18F-FDG-PET. Materials and Methods Patients with untreated histologically verified MALT lymphoma, who were undergoing pretherapeutic 18F-FDG-PET/computed tomography (CT) and consecutive 18F-FDG-PET/magnetic resonance imaging (MRI), using a single 18F-FDG injection, in the course of a larger-scale prospective trial, were included. Region-based sensitivity and specificity, and patient-based sensitivity of the respective 18F-FDG-PET scans at time points 1 (45–60 minutes after tracer injection, TP1) and 2 (100–150 minutes after tracer injection, TP2), relative to the reference standard, were calculated. Lesion-to-liver and lesion-to-blood SUVmax (maximum standardized uptake values) ratios were also assessed. Results 18F-FDG-PET at TP1 was true positive in 15 o f 23 involved regions, and 18F-FDG-PET at TP2 was true-positive in 20 of 23 involved regions; no false-positive regions were noted. Accordingly, region-based sensitivities and specificities were 65.2% (confidence interval [CI], 45.73%–84.67%) and 100% (CI, 100%-100%) for 18F-FDG-PET at TP1; and 87.0% (CI, 73.26%–100%) and 100% (CI, 100%-100%) for 18F-FDG-PET at TP2, respectively. FDG-PET at TP1 detected lymphoma in at least one nodal or extranodal region in 7 of 13 patients, and 18F-FDG-PET at TP2 in 10 of 13 patients; accordingly, patient-based sensitivity was 53.8% (CI, 26.7%–80.9%) for 18F-FDG-PET at TP1, and 76.9% (CI, 54.0%–99.8%) for 18F-FDG-PET at TP2. Lesion-to-liver and lesion-to-blood maximum standardized uptake value ratios were significantly lower at TP1 (ratios, 1.05 ± 0.40 and 1.52 ± 0.62) than at TP2 (ratios, 1.67 ± 0.74 and 2.56 ± 1.10; P = 0.003 and P = 0.001). Conclusions Delayed–time-point imaging may improve 18F-FDG-PET in MALT lymphoma. PMID:26402137

Classification of TP53 Mutations and HPV Predict Survival in Advanced Larynx Cancer

PubMed Central

Scheel, Adam; Bellile, Emily; McHugh, Jonathan B.; Walline, Heather M.; Prince, Mark E.; Urba, Susan; Wolf, Gregory T.; Eisbruch, Avraham; Worden, Francis; Carey, Thomas E.; Bradford, Carol

2016-01-01

OBJECTIVE Assess TP53 functional mutations in the context of other biomarkers in advanced larynx cancer. STUDY DESIGN Prospective analysis of pretreatment tumor TP53, HPV, Bcl-xL and cyclin D1 status in stage III and IV larynx cancer patients in a clinical trial. METHODS TP53 exons 4-9 from 58 tumors were sequenced. Mutations were grouped using three classifications based on their expected function. Each functional group was analyzed for response to induction chemotherapy, time to surgery, survival, HPV status, p16INK4a, Bcl-xl and cyclin D1 expression. RESULTS TP53 Mutations were found in 22/58 (37.9%) patients with advanced larynx cancer, including missense mutations in 13/58 (22.4%) patients, nonsense mutations in 4/58 (6.9%), and deletions in 5/58 (8.6%). High risk HPV was found in 20/52 (38.5%) tumors. A classification based on crystal Evolutionary Action score of p53 (EAp53) distinguished missense mutations with high risk for decreased survival from low risk mutations (p=0.0315). A model including this TP53 classification, HPV status, cyclin D1 and Bcl-xL staining significantly predicts survival (p=0.0017). CONCLUSION EAp53 functional classification of TP53 mutants and biomarkers predict survival in advanced larynx cancer. PMID:27345657

Worksite Tobacco Prevention: A Randomized, Controlled Trial of Adoption, Dissemination Strategies, and Aggregated Health-Related Outcomes across Companies.

PubMed

Friedrich, Verena; Brügger, Adrian; Bauer, Georg F

2015-01-01

Evidence based public health requires knowledge about successful dissemination of public health measures. This study analyses (a) the changes in worksite tobacco prevention (TP) in the Canton of Zurich, Switzerland, between 2007 and 2009; (b1) the results of a multistep versus a "brochure only" dissemination strategy; (b2) the results of a monothematic versus a comprehensive dissemination strategy that aim to get companies to adopt TP measures; and (c) whether worksite TP is associated with health-related outcomes. A longitudinal design with randomized control groups was applied. Data on worksite TP and health-related outcomes were gathered by a written questionnaire (baseline n = 1627; follow-up n = 1452) and analysed using descriptive statistics, nonparametric procedures, and ordinal regression models. TP measures at worksites improved slightly between 2007 and 2009. The multistep dissemination was superior to the "brochure only" condition. No significant differences between the monothematic and the comprehensive dissemination strategies were observed. However, improvements in TP measures at worksites were associated with improvements in health-related outcomes. Although dissemination was approached at a mass scale, little change in the advocated adoption of TP measures was observed, suggesting the need for even more aggressive outreach or an acceptance that these channels do not seem to be sufficiently effective.

Evaluation of the HISCL Anti-Treponema pallidum Assay as a Screening Test for Syphilis

PubMed Central

An, Jingna; Chen, Qixia; Liu, Qianqian; Rao, Chenli; Li, Dongdong; Wang, Tingting

2015-01-01

The resurgence of syphilis in recent years has become a serious threat to public health worldwide, and the serological detection of specific antibodies against Treponema pallidum remains the most reliable method for laboratory diagnosis of syphilis. This study examined the performance of the recently launched HISCL anti-Treponema pallidum (anti-TP) assay as a screening test for syphilis in a high-volume laboratory. The HISCL anti-TP assay was tested in 300 preselected syphilis-positive samples, 704 fresh syphilis-negative samples, 48 preselected potentially interfering samples, and 30 “borderline” samples and was compared head to head with the commercially available Lumipulse G TP-N. In this study, the HISCL anti-TP assay was in perfect agreement with the applied testing algorithms with an overall agreement of 100%, comparable to that of Lumipulse G TP-N (99.63%). The sensitivity and specificity of the HISCL anti-TP assay were 100% (95% confidence interval [CI], 98.42% to 100%) and 100% (95% CI, 99.37% to 100%), respectively. Considering the excellent ease of use and automation, high throughput, and its favorable sensitivity and specificity, the HISCL anti-TP assay may represent a new choice for syphilis screening in high-volume laboratories. PMID:25972403

Evaluation of the HISCL Anti-Treponema pallidum Assay as a Screening Test for Syphilis.

PubMed

An, Jingna; Chen, Qixia; Liu, Qianqian; Rao, Chenli; Li, Dongdong; Wang, Tingting; Tao, Chuanmin; Wang, Lanlan

2015-07-01

The resurgence of syphilis in recent years has become a serious threat to public health worldwide, and the serological detection of specific antibodies against Treponema pallidum remains the most reliable method for laboratory diagnosis of syphilis. This study examined the performance of the recently launched HISCL anti-Treponema pallidum (anti-TP) assay as a screening test for syphilis in a high-volume laboratory. The HISCL anti-TP assay was tested in 300 preselected syphilis-positive samples, 704 fresh syphilis-negative samples, 48 preselected potentially interfering samples, and 30 "borderline" samples and was compared head to head with the commercially available Lumipulse G TP-N. In this study, the HISCL anti-TP assay was in perfect agreement with the applied testing algorithms with an overall agreement of 100%, comparable to that of Lumipulse G TP-N (99.63%). The sensitivity and specificity of the HISCL anti-TP assay were 100% (95% confidence interval [CI], 98.42% to 100%) and 100% (95% CI, 99.37% to 100%), respectively. Considering the excellent ease of use and automation, high throughput, and its favorable sensitivity and specificity, the HISCL anti-TP assay may represent a new choice for syphilis screening in high-volume laboratories. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Novel characteristics of a carbohydrate-binding module 20 from hyperthermophilic bacterium.

PubMed

Oh, Il-Nam; Jane, Jay-Lin; Wang, Kan; Park, Jong-Tae; Park, Kwan-Hwa

2015-03-01

In this study, a gene fragment coding carbohydrate-binding module 20 (CBM20) in the amylopullulanase (APU) gene was cloned from the hyperthermophilic bacteria Thermoanaerobacter pseudoethanolicus 39E and expressed in Escherichia coli. The protein, hereafter Tp39E, possesses very low sequence similarity with the CBM20s previously reported and has no starch binding site 2. Tp39E did not demonstrate thermal denaturation at 50 °C; however, thermal unfolding of the protein was observed at 59.5 °C. A binding assay with Tp39E was conducted using various soluble and insoluble substrates, and starch was the best binding polysaccharide. Intriguingly, Tp39E bound, to a lesser extent, to soluble and insoluble xylan as well. The dissociation constant (K d) and the maximum specific binding (B max) of Tp39E to corn starch granules were 0.537 μM and 5.79 μM/g, respectively, at pH 5.5 and 20 °C. 99APU1357 with a Tp39E domain exhibited 2.2-fold greater activity than a CBM20-truncation mutant when starch granules were the substrate. Tp39E was an independently thermostable CBM and had a considerable effect on APU activity in the hydrolysis of insoluble substrates.

Small-molecule inhibitors of phosphatidylcholine transfer protein/StarD2 identified by high-throughput screening.

PubMed

Wagle, Neil; Xian, Jun; Shishova, Ekaterina Y; Wei, Jie; Glicksman, Marcie A; Cuny, Gregory D; Stein, Ross L; Cohen, David E

2008-12-01

Phosphatidylcholine transfer protein (PC-TP, also referred to as StarD2) is a highly specific intracellular lipid-binding protein that catalyzes the transfer of phosphatidylcholines between membranes in vitro. Recent studies have suggested that PC-TP in vivo functions to regulate fatty acid and glucose metabolism, possibly via interactions with selected other proteins. To begin to address the relationship between activity in vitro and biological function, we undertook a high-throughput screen to identify small-molecule inhibitors of the phosphatidylcholine transfer activity of PC-TP. After adapting a fluorescence quench assay to measure phosphatidylcholine transfer activity, we screened 114,752 compounds of a small-molecule library. The high-throughput screen identified 14 potential PC-TP inhibitors. Of these, 6 compounds exhibited characteristics consistent with specific inhibition of PC-TP activity, with IC(50) values that ranged from 4.1 to 95.0muM under conditions of the in vitro assay. These compounds should serve as valuable reagents to elucidate the biological function of PC-TP. Because mice with homozygous disruption of the PC-TP gene (Pctp) are sensitized to insulin action and relatively resistant to the development of atherosclerosis, these inhibitors may also prove to be of value in the management of diabetes and atherosclerotic cardiovascular diseases.

Gravity model development for TOPEX/POSEIDON: Joint gravity models 1 and 2

NASA Technical Reports Server (NTRS)

Nerem, R. S.; Lerch, F. J.; Marshall, J. A.; Pavlis, E. C.; Putney, B. H.; Tapley, B. D.; Eanes, R. J.; Ries, J. C.; Schutz, B. E.; Shum, C. K.

1994-01-01

The TOPEX/POSEIDON (T/P) prelaunch Joint Gravity Model-1 (JGM-1) and the postlaunch JGM-2 Earth gravitational models have been developed to support precision orbit determination for T/P. Each of these models is complete to degree 70 in spherical harmonics and was computed from a combination of satellite tracking data, satellite altimetry, and surface gravimetry. While improved orbit determination accuracies for T/P have driven the improvements in the models, the models are general in application and also provide an improved geoid for oceanographic computations. The postlaunch model, JGM-2, which includes T/P satellite laser ranging (SLR) and Doppler orbitography and radiopositioning integrated by satellite (DORIS) tracking data, introduces radial orbit errors for T/P that are only 2 cm RMS with the commission errors of the marine geoid for terms to degree 70 being +/- 25 cm. Errors in modeling the nonconservative forces acting on T/P increase the total radial errors to only 3-4 cm root mean square (RMS), a result much better than premission goals. While the orbit accuracy goal for T/P has been far surpassed geoid errors still prevent the absolute determination of the ocean dynamic topography for wavelengths shorter than about 2500 km. Only a dedicated gravitational field satellite mission will likely provide the necessary improvement in the geoid.

Thin-layer preparations of dithiothreitol-treated bronchial washing specimens.

PubMed

Koivurinne, Kirsti I; Shield, Paul W

2003-01-01

To evaluate the combined effect of dithiothreitol (DTT) treatment and ThinPrep (TP) (Cytyc Corp, Boxborough, Massachusetts, U.S.A.) processing on bronchial washing specimens. A total of 431 bronchial washing specimens were initially treated with 0.05% DTT in a 30% methanol solution. After centrifugation, 1 TP slide and 2-4 conventional cytospin or smear preparations (CPs) were prepared. The reports of both preparations were compared in all cases. All 48 abnormal cases and 52 consecutive negative cases were also compared for cellular composition, distribution of the cells, ease of interpretation and overall preparation quality. Screening time was recorded for 20 of the cases. The diagnostic accuracy of one TP slide appeared comparable to that of 2-4 CPs. The TP slide was assessed to be equal or superior in overall quality to CP in 85% of 100 cases of paired specimens. The cleaner background and smaller cellular area of TP slides significantly reduced the screening time. Mucolysis and specimen homogenization were not always optimal, occasionally resulting in uneven subsampling and poorly cellular TPs. However, in general, TP slides were considered superior to CPs in overall quality. Improvement in specimen quality and reduced screening time have to be balanced against the high cost of consumables with the TP technique.

The immediate and long-term effects of time perspective on Internet gaming disorder.

PubMed

Lukavská, Kateřina

2018-03-01

Backgrounds and aims This study focuses on the role of time perspective (TP) in Internet gaming disorder (IGD). An inventory-based study on 377 massive multiplayer online role playing game players was conducted, followed by a 3-year-follow-up in which 48 active players from the original sample participated. We proposed that TP factors (negative TP and future positive TP) will influence either the current presence of IGD symptoms or the further development of IGD over time. In other words, the effect of TP is stable. Finally, game usage patterns were analyzed in the sense of changes in playing time and IGD symptoms in gamers after 3 years. Methods To access the variables, two scales were administered through online inventory, the Zimbardo Time Perspective Inventory-short, and Charlton and Danforths' Core Addiction Scale, both in 2012 (N = 377) and 2015 (N = 48). The amount of time that gamers usually spent playing were obtained through self-reports. Results The study's primary presumptions were confirmed. Both negative TP and future positive TP were confirmed as significant predictors of the presence of IGD symptoms, either immediately or in the following 3 years. Data on game usage showed a significant decrease in playing time and IGD symptoms between year 0 and year 3 of the study.

Worksite Tobacco Prevention: A Randomized, Controlled Trial of Adoption, Dissemination Strategies, and Aggregated Health-Related Outcomes across Companies

PubMed Central

Friedrich, Verena; Brügger, Adrian; Bauer, Georg F.

2015-01-01

Evidence based public health requires knowledge about successful dissemination of public health measures. This study analyses (a) the changes in worksite tobacco prevention (TP) in the Canton of Zurich, Switzerland, between 2007 and 2009; (b1) the results of a multistep versus a “brochure only” dissemination strategy; (b2) the results of a monothematic versus a comprehensive dissemination strategy that aim to get companies to adopt TP measures; and (c) whether worksite TP is associated with health-related outcomes. A longitudinal design with randomized control groups was applied. Data on worksite TP and health-related outcomes were gathered by a written questionnaire (baseline n = 1627; follow-up n = 1452) and analysed using descriptive statistics, nonparametric procedures, and ordinal regression models. TP measures at worksites improved slightly between 2007 and 2009. The multistep dissemination was superior to the “brochure only” condition. No significant differences between the monothematic and the comprehensive dissemination strategies were observed. However, improvements in TP measures at worksites were associated with improvements in health-related outcomes. Although dissemination was approached at a mass scale, little change in the advocated adoption of TP measures was observed, suggesting the need for even more aggressive outreach or an acceptance that these channels do not seem to be sufficiently effective. PMID:26504778

Painful Heat Reveals Hyperexcitability of the Temporal Pole in Interictal and Ictal Migraine States

PubMed Central

Moulton, E. A.; Becerra, L.; Maleki, N.; Pendse, G.; Tully, S.; Hargreaves, R.; Burstein, R.

2011-01-01

During migraine attacks, alterations in sensation accompanying headache may manifest as allodynia and enhanced sensitivity to light, sound, and odors. Our objective was to identify physiological changes in cortical regions in migraine patients using painful heat and functional magnetic resonance imaging (fMRI) and the structural basis for such changes using diffusion tensor imaging (DTI). In 11 interictal patients, painful heat threshold + 1°C was applied unilaterally to the forehead during fMRI scanning. Significantly greater activation was identified in the medial temporal lobe in patients relative to healthy subjects, specifically in the anterior temporal pole (TP). In patients, TP showed significantly increased functional connectivity in several brain regions relative to controls, suggesting that TP hyperexcitability may contribute to functional abnormalities in migraine. In 9 healthy subjects, DTI identified white matter connectivity between TP and pulvinar nucleus, which has been related to migraine. In 8 patients, fMRI activation in TP with painful heat was exacerbated during migraine, suggesting that repeated migraines may sensitize TP. This article investigates a nonclassical role of TP in migraineurs. Observed temporal lobe abnormalities may provide a basis for many of the perceptual changes in migraineurs and may serve as a potential interictal biomarker for drug efficacy. PMID:20562317

Association of mRNA expression of TP53 and the TP53 codon 72 Arg/Pro gene polymorphism with colorectal cancer risk in Asian population: a bioinformatics analysis and meta-analysis.

PubMed

Dong, Zhiyong; Zheng, Longzhi; Liu, Weimin; Wang, Cunchuan

2018-01-01

The relationship between TP53 codon 72 Pro/Arg gene polymorphism and colorectal cancer risk in Asians is still controversial, and this bioinformatics analysis and meta-analysis was performed to assess the associations. The association studies were identified from PubMed, and eligible reports were included. RevMan 5.3.1 software, Oncolnc, cBioPortal, and Oncomine online tools were used for statistical analysis. A random/fixed effects model was used in meta-analysis. The data were reported as risk ratios or mean differences with corresponding 95% CI. We confirmed that TP53 was associated with colorectal cancer, the alteration frequency of TP53 was 53% mutation and 7% deep deletion, and TP53 mRNA expression was different in different types of colorectal cancer based on The Cancer Genome Atlas database. Then, 18 studies were included that examine the association of TP53 codon 72 gene polymorphism with colorectal cancer risk in Asians. The meta-analysis indicated that TP53 Pro allele and Pro/Pro genotype were associated with colorectal cancer risk in Asian population, but Arg/Arg genotype was not (Pro allele: odds ratios [OR]=1.20, 95% CI: 1.06 to 1.35, P =0.003; Pro/Pro genotype: OR=1.39, 95% CI: 1.15 to 1.69, P =0.0007; Arg/Arg genotype: OR=0.86, 95% CI: 0.74 to 1.00, P =0.05). Interestingly, in the meta-analysis of the controls from the population-based studies, we found that TP53 codon 72 Pro/Arg gene polymorphism was associated with colorectal cancer risk (Pro allele: OR=1.33, 95% CI: 1.15 to 1.55, P =0.0002; Pro/Pro genotype: OR=1.61, 95% CI: 1.28 to 2.02, P <0.0001; Arg/Arg genotype: OR=0.77, 95% CI: 0.63 to 0.93, P =0.009). TP53 was associated with colorectal cancer, but the different value levels of mRNA expression were not associated with survival rate of colon and rectal cancer. TP53 Pro allele and Pro/Pro genotype were associated with colorectal cancer risk in Asians.

Reductive elimination/oxidative addition of carbon-hydrogen bonds at Pt(IV)/Pt(II) centers: mechanistic studies of the solution thermolyses of Tp(Me2)Pt(CH3)2H.

PubMed

Jensen, Michael P; Wick, Douglas D; Reinartz, Stefan; White, Peter S; Templeton, Joseph L; Goldberg, Karen I

2003-07-16

Reductive elimination of methane occurs upon solution thermolysis of kappa(3)-Tp(Me)2Pt(IV)(CH(3))(2)H (1, Tp(Me)2 = hydridotris(3,5-dimethylpyrazolyl)borate). The platinum product of this reaction is determined by the solvent. C-D bond activation occurs after methane elimination in benzene-d(6), to yield kappa(3)-Tp(Me)2Pt(IV)(CH(3))(C(6)D(5))D (2-d(6)), which undergoes a second reductive elimination/oxidative addition reaction to yield isotopically labeled methane and kappa(3)-Tp(Me)2Pt(IV)(C(6)D(5))(2)D (3-d(11)). In contrast, kappa(2)-Tp(Me)2Pt(II)(CH(3))(NCCD(3)) (4) was obtained in the presence of acetonitrile-d(3), after elimination of methane from 1. Reductive elimination of methane from these Pt(IV) complexes follows first-order kinetics, and the observed reaction rates are nearly independent of solvent. Virtually identical activation parameters (DeltaH(++)(obs) = 35.0 +/- 1.1 kcal/mol, DeltaS(++)(obs) = 13 +/- 3 eu) were measured for the reductive elimination of methane from 1 in both benzene-d(6) and toluene-d(8). A lower energy process (DeltaH(++)(scr) = 26 +/- 1 kcal/mol, DeltaS(++)(scr) = 1 +/- 4 eu) scrambles hydrogen atoms of 1 between the methyl and hydride positions, as confirmed by monitoring the equilibration of kappa(3)-Tp(Me)()2Pt(IV)(CH(3))(2)D (1-d(1)()) with its scrambled isotopomer, kappa(3)-Tp(Me)2Pt(IV)(CH(3))(CH(2)D)H (1-d(1'). The sigma-methane complex kappa(2)-Tp(Me)2Pt(II)(CH(3))(CH(4)) is proposed as a common intermediate in both the scrambling and reductive elimination processes. Kinetic results are consistent with rate-determining dissociative loss of methane from this intermediate to produce the coordinatively unsaturated intermediate [Tp(Me)2Pt(II)(CH(3))], which reacts rapidly with solvent. The difference in activation enthalpies for the H/D scrambling and C-H reductive elimination provides a lower limit for the binding enthalpy of methane to [Tp(Me)2Pt(II)(CH(3))] of 9 +/- 2 kcal/mol.

Association of mRNA expression of TP53 and the TP53 codon 72 Arg/Pro gene polymorphism with colorectal cancer risk in Asian population: a bioinformatics analysis and meta-analysis

PubMed Central

Liu, Weimin; Wang, Cunchuan

2018-01-01

Background The relationship between TP53 codon 72 Pro/Arg gene polymorphism and colorectal cancer risk in Asians is still controversial, and this bioinformatics analysis and meta-analysis was performed to assess the associations. Methods The association studies were identified from PubMed, and eligible reports were included. RevMan 5.3.1 software, Oncolnc, cBioPortal, and Oncomine online tools were used for statistical analysis. A random/fixed effects model was used in meta-analysis. The data were reported as risk ratios or mean differences with corresponding 95% CI. Results We confirmed that TP53 was associated with colorectal cancer, the alteration frequency of TP53 was 53% mutation and 7% deep deletion, and TP53 mRNA expression was different in different types of colorectal cancer based on The Cancer Genome Atlas database. Then, 18 studies were included that examine the association of TP53 codon 72 gene polymorphism with colorectal cancer risk in Asians. The meta-analysis indicated that TP53 Pro allele and Pro/Pro genotype were associated with colorectal cancer risk in Asian population, but Arg/Arg genotype was not (Pro allele: odds ratios [OR]=1.20, 95% CI: 1.06 to 1.35, P=0.003; Pro/Pro genotype: OR=1.39, 95% CI: 1.15 to 1.69, P=0.0007; Arg/Arg genotype: OR=0.86, 95% CI: 0.74 to 1.00, P=0.05). Interestingly, in the meta-analysis of the controls from the population-based studies, we found that TP53 codon 72 Pro/Arg gene polymorphism was associated with colorectal cancer risk (Pro allele: OR=1.33, 95% CI: 1.15 to 1.55, P=0.0002; Pro/Pro genotype: OR=1.61, 95% CI: 1.28 to 2.02, P<0.0001; Arg/Arg genotype: OR=0.77, 95% CI: 0.63 to 0.93, P=0.009). Conclusion TP53 was associated with colorectal cancer, but the different value levels of mRNA expression were not associated with survival rate of colon and rectal cancer. TP53 Pro allele and Pro/Pro genotype were associated with colorectal cancer risk in Asians. PMID:29872345

ROS Modifiers and NOX4 Affect the Expression of the Survivin-Associated Radio-Adaptive Response.

PubMed

Murley, Jeffrey S; Arbiser, Jack L; Weichselbaum, Ralph R; Grdina, David J

2018-04-13

The survivin-associated radio-adaptive response can be induced following exposure to ionizing radiation in the dose range from 5 to 100 mGy, and its magnitude of expression is dependent upon the TP53 mutational status of cells and ROS signaling. The purpose of the study was to investigate the potential role of ROS in the development of the survivin-associated adaptive response. Utilizing human colon carcinoma HCT116 TP53 wild type (WT) and HCT116 isogenic TP53 null mutant (Mut) cell cultures, the roles of inter- and intracellular ROS signaling on expression of the adaptive response as evidenced by changes in intracellular translocation of survivin measured by ELISA, and cell survival determined by a standard colony forming assay were investigated using ROS modifying agents that include emodin, N-acetyl-l-cysteine (NAC), fulvene-5, honokiol, metformin and rotenone. The role of NADPH oxidase 4 (NOX4) in the survivin-associated adaptive response was investigated by transfecting HCT116 cells, both WT and Mut, with two different NOX4 siRNA oligomers and Western blotting. A dose of 5 mGy or a 15min exposure to 50µM of the ROS producing drug emodin were equally effective in inducing a pro-survival adaptive response in TP53 WT and a radio-sensitization adaptive response in TP53 Mut HCT116 cells. Each response was associated with a corresponding translocation of survivin into the cytoplasm or nucleus, respectively. Exposure to 10mM NAC completely inhibited both responses. Exposure to 10µM honokiol induced responses similar to those observed following NAC exposure in TP53 WT and Mut cells. The mitochondrial complex 1 inhibitor rotenone was effective in reducing both cytoplasmic and nuclear survivin levels, but was ineffective in altering the expression of the adaptive response in either TP53 WT or Mut cells. In contrast, both metformin and fulvene-5, inhibitors of NOX4, facilitated the reversal of TP53 WT and Mut adaptive responses from pro-survival to radio-sensitization and vice versa, respectively. These changes were accompanied by corresponding reversals in the translocation of survivin to the nuclei of TP53 WT and to the cytoplasm of TP53 Mut cells. The potential role of NOX4 in the expression of the survivin-associated adaptive response was investigated by transfecting HCT116 cells with NOX4 siRNA oligomers to inhibit NOX4 expression. Under these conditions NOX4 expression was inhibited by about 50%, resulting in a reversal in the expression of the TP53 WT and Mut survivin-associated adaptive responses as was observed following metformin and fulvene-5 treatment. Exposure to 5 mGy resulted in enhanced NOX4 expression by about 40% in both TP53 WT and Mut cells, in contrast to only a 1 to 2% increase following a 2Gy only exposure. Utilizing mixed cultures of HCT116 TP53 WT and isogenic null Mut cells, as few as 10% TP53 Mut cells were sufficient to control the expression of the remaining 90% WT cells and resulted in an overall radio-sensitization response accompanied by the nuclear translocation of survivin characteristic of homogeneous TP53 Mut populations. Copyright © 2018. Published by Elsevier Inc.

Critical androgen-sensitive periods of rat penis and clitoris development

PubMed Central

Welsh, Michelle; MacLeod, David J; Walker, Marion; Smith, Lee B; Sharpe, Richard M

2010-01-01

Androgen control of penis development/growth is unclear. In rats, androgen action in a foetal ‘masculinisation programming window’ (MPW; e15.5–e18.5)’ predetermines penile length and hypospadias occurrence. This has implications for humans (e.g. micropenis). Our studies aimed to establish in rats when androgen action/administration affects development/growth of the penis and if deficits in MPW androgen action were rescuable postnatally. Thus, pregnant rats were treated with flutamide during the MPW ± postnatal testosterone propionate (TP) treatment. To assess penile growth responsiveness, rats were treated with TP in various time windows (late foetal, neonatal through early puberty, puberty onset, or combinations thereof). Phallus length, weight, and morphology, hypospadias and anogenital distance (AGD) were measured in mid-puberty (d25) or adulthood (d90) in males and females, plus serum testosterone in adult males. MPW flutamide exposure reduced adult penile length and induced hypospadias dose-dependently; this was not rescued by postnatal TP treatment. In normal rats, foetal (e14.5–e21.5) TP exposure did not affect male penis size but increased female clitoral size. In males, TP exposure from postnatal d1–24 or at puberty (d15–24), increased penile length at d25, but not ultimately in adulthood. Foetal + postnatal TP (e14–postnatal d24) increased penile size at d25 but reduced it at d90 (due to reduced endogenous testosterone). In females, this treatment caused the biggest increase in adult clitoral size but, unlike in males, phallus size was unaffected by TP during puberty (d15–24). Postnatal TP treatment advanced penile histology at d25 to more resemble adult histology. AGD strongly correlated with final penis length. It is concluded that adult penile size depends critically on androgen action during the MPW but subsequent growth depends on later androgen exposure. Foetal and/or postnatal TP exposure does not increase adult penile size above its ‘predetermined’ length though its growth towards this maximum is advanced by peripubertal TP treatment. PMID:19656234

Conformational Changes in a Hyperthermostable Glycoside Hydrolase: Enzymatic Activity Is a Consequence of the Loop Dynamics and Protonation Balance

PubMed Central

de Oliveira, Leandro C.; da Silva, Viviam M.; Colussi, Francieli; Cabral, Aline D.; de Oliveira Neto, Mario; Squina, Fabio M.; Garcia, Wanius

2015-01-01

Endo-β-1, 4-mannanase from Thermotoga petrophila (TpMan) is a modular hyperthermostable enzyme involved in the degradation of mannan-containing polysaccharides. The degradation of these polysaccharides represents a key step for several industrial applications. Here, as part of a continuing investigation of TpMan, the region corresponding to the GH5 domain (TpManGH5) was characterized as a function of pH and temperature. The results indicated that the enzymatic activity of the TpManGH5 is pH-dependent, with its optimum activity occurring at pH 6. At pH 8, the studies demonstrated that TpManGH5 is a molecule with a nearly spherical tightly packed core displaying negligible flexibility in solution, and with size and shape very similar to crystal structure. However, TpManGH5 experiences an increase in radius of gyration in acidic conditions suggesting expansion of the molecule. Furthermore, at acidic pH values, TpManGH5 showed a less globular shape, probably due to a loop region slightly more expanded and flexible in solution (residues Y88 to A105). In addition, molecular dynamics simulations indicated that conformational changes caused by pH variation did not change the core of the TpManGH5, which means that only the above mentioned loop region presents high degree of fluctuations. The results also suggested that conformational changes of the loop region may facilitate polysaccharide and enzyme interaction. Finally, at pH 6 the results indicated that TpManGH5 is slightly more flexible at 65°C when compared to the same enzyme at 20°C. The biophysical characterization presented here is well correlated with the enzymatic activity and provide new insight into the structural basis for the temperature and pH-dependent activity of the TpManGH5. Also, the data suggest a loop region that provides a starting point for a rational design of biotechnological desired features. PMID:25723179

On the origin and destination of atmospheric moisture and air mass over the Tibetan Plateau

NASA Astrophysics Data System (ADS)

Chen, Bin; Xu, Xiang-De; Yang, Shuai; Zhang, Wei

2012-12-01

The Tibet Plateau (TP) is a key region that imposes profound impacts on the atmospheric water cycle and energy budget of Asia, even the global climate. In this work, we develop a climatology of origin (destination) of air mass and moisture transported to (from) the TP using a Lagrangian moisture diagnosis combined with the forward and backward atmospheric tracking schemes. The climatology is derived from 6-h particle positions based on 5-year (2005-2009) seasonal summer trajectory dataset from the Lagrangian particle dispersion model FLEXPART using NCEP/GFS data as input, where the regional model atmosphere was globally filled with particles. The results show that (1) the dominant origin of the moisture supplied to the TP is a narrow tropical-subtropical band in the extended Arabian Sea covering a long distance from the Indian subcontinent to the Southern Hemisphere. Two additional moisture sources are located in the northwestern part of TP and the Bay of Bengal and play a secondary role. This result indicates that the moisture transporting to the TP more depends on the Indian summer monsoon controlled by large-scale circulation. (2) The moisture departing from the TP can be transported rapidly to East Asia, including East China, Korea, Japan, and even East Pacific. The qualitative similarity between the regions of diagnosed moisture loss and the pattern of the observed precipitation highlights the robustness of the role of the TP on precipitation over East Asia. (3) In contrast to the moisture origin confined in the low level, the origin and fate of whole column air mass over the TP is largely controlled by a strong high-level Asian anticyclone. The results show that the TP is a crossroad of air mass where air enters mainly from the northwest and northeast and continues in two separate streams: one goes southwestwards over the Indian Ocean and the other southeastwards through western North Pacific. Both of them partly enter the trade wind zone, which manifests the influence of the air mass transport over the TP on the budget of global atmosphere compositions.

Bulk Lorentz factors of gamma-ray bursts

NASA Astrophysics Data System (ADS)

Ghirlanda, G.; Nappo, F.; Ghisellini, G.; Melandri, A.; Marcarini, G.; Nava, L.; Salafia, O. S.; Campana, S.; Salvaterra, R.

2018-01-01

Knowledge of the bulk Lorentz factor Γ0 of gamma-ray bursts (GRBs) allows us to compute their comoving frame properties shedding light on their physics. Upon collisions with the circumburst matter, the fireball of a GRB starts to decelerate, producing a peak or a break (depending on the circumburst density profile) in the light curve of the afterglow. Considering all bursts with known redshift and with an early coverage of their emission, we find 67 GRBs (including one short event) with a peak in their optical or GeV light curves at a time tp. For another 106 GRBs we set an upper limit tpUL. The measure of tp provides the bulk Lorentz factor Γ0 of the fireball before deceleration. We show that tp is due to the dynamics of the fireball deceleration and not to the passage of a characteristic frequency of the synchrotron spectrum across the optical band. Considering the tp of 66 long GRBs and the 85 most constraining upper limits, we estimate Γ0 or a lower limit Γ0LL. Using censored data analysis methods, we reconstruct the most likely distribution of tp. All tp are larger than the time Tp,γ when the prompt γ-ray emission peaks, and are much larger than the time Tph when the fireball becomes transparent, that is, tp>Tp,γ>Tph. The reconstructed distribution of Γ0 has median value 300 (150) for a uniform (wind) circumburst density profile. In the comoving frame, long GRBs have typical isotropic energy, luminosity, and peak energy ⟨ Eiso ⟩ = 3(8) × 1050 erg, ⟨ Liso ⟩ = 3(15) × 1047 erg s-1, and ⟨ Epeak ⟩ = 1(2) keV in the homogeneous (wind) case. We confirm that the significant correlations between Γ0 and the rest frame isotropic energy (Eiso), luminosity (Liso), and peak energy (Ep) are not due to selection effects. When combined, they lead to the observed Ep-Eiso and Ep-Liso correlations. Finally, assuming a typical opening angle of 5 degrees, we derive the distribution of the jet baryon loading which is centered around a few 10-6M⊙.

KRAS and TP53 mutations in inflammatory bowel disease-associated colorectal cancer: a meta-analysis

PubMed Central

Du, Lijun; Kim, John J.; Shen, Jinhua; Chen, Binrui; Dai, Ning

2017-01-01

Although KRAS and TP53 mutations are common in both inflammatory bowel disease-associated colorectal cancer (IBD-CRC) and sporadic colorectal cancer (S-CRC), molecular events leading to carcinogenesis may be different. Previous studies comparing the frequency of KRAS and TP53 mutations in IBD-CRC and S-CRC were inconsistent. We performed a meta-analysis to compare the presence of KRAS and TP53 mutations among patients with IBD-CRC, S-CRC, and IBD without dysplasia. A total of 19 publications (482 patients with IBD-CRC, 4,222 with S-CRC, 281 with IBD without dysplasia) met the study inclusion criteria. KRAS mutation was less frequent (RR=0.71, 95%CI 0.56-0.90; P=0.004) while TP53 mutation was more common (RR=1.24, 95%CI 1.10-1.39; P<0.001) in patients with IBD-CRC compared to S-CRC. Both KRAS (RR=3.09, 95%CI 1.47-6.51; P=0.003) and TP53 (RR=2.15, 95%CI 1.07-4.31 P=0.03) mutations were more prevalent in patients with IBD-CRC compared to IBD without dysplasia. In conclusion, IBD-CRC and S-CRC appear to have biologically different molecular pathways. TP53 appears to be more important than KRAS in IBD-CRC compared to S-CRC. Our findings suggest possible roles of TP53 and KRAS as biomarkers for cancer and dysplasia screening among patients with IBD and may also provide targeted therapy in patients with IBD-CRC. PMID:28077799

Comparison of ThinPrep and conventional preparations on fine needle aspiration cytology material.

PubMed

Dey, P; Luthra, U K; George, J; Zuhairy, F; George, S S; Haji, B I

2000-01-01

To compare the various cytologic features on ThinPrep 2000 (TP) (Cytyc Corporation, Marlborough, Massachusetts, U.S.A.) and conventional preparation (CP) specimens from fine needle aspiration cytology (FNAC) material by a semiquantitative scoring system. In this prospective study a total of 71 consecutive cases were included. In each case, two passes were performed. The first pass was used for conventional preparations, with direct smears made and fixed immediately in 95% alcohol for Papanicolaou stain. For TP preparation a second pass produced material for processing in the ThinPrep 2000. The TP and CP slides were studied independently by two observers and representative slides of CP and TP compared for cellularity, background blood and necrotic cell debris, cell architecture, informative background, presence of monolayer cells, and nuclear and cytoplasmic details by a semiquantitative scoring system. Statistical analysis was performed by Wilcoxon's signed rank test on an SPSS program (Chicago, Illinois, U.S.A.). TP preparations contained adequate diagnostic cells in all cases and were tangibly superior to CP preparations concerning monolayer cells, absence of blood and necrosis, and preservation of nuclear and cytoplasmic detail (statistically significant, Wilcoxon's signed rank test, P < .000). TP preparations are superior to conventional preparations with regard to clear background, monolayer cell preparation and cell preservation. It is easier and less time consuming to screen and interpret TP preparations because the cells are limited to smaller areas on clear backgrounds, with excellent cellular preservation. However, TP preparations are more expensive than CP and require some experience for interpretation.

Transverse process anatomy as a guide to vertebral artery exposure during anterior cervical spine approach: A Cadaveric Study.

PubMed

Nourbakhsh, Ali; Yang, Jinping; Mcmahan, Howard; Garges, Kim

2017-05-01

Safe exposure of the vertebral artery (VA) is needed during resection of tumors close to the artery and during repair of lacerations. We defined the anatomy of the anterior root of each transverse process (TP) from C3 to C6 for identification and exposure of the VA during the anterior approach. We examined the anatomy of the TP and assessed two approaches for safe identification of the VA, lateral to medial and medial to lateral dissection of the TP, in 20 cadavers. The safe zone at each level of the cervical spine was defined as an area in which the surgeon can start to dissect at the midline of that level on the TP and safely cross the VA laterally. For the lateral to medial approach the surgical safe zone lies between the mid axis of the TPs and a line 2 mm parallel to and above it. The average TP angle was 11 ± 10.2 degrees. The mean distance of the lateral border of the VA from the TP tip was 3.78-5.28 mm. For the medial to lateral approach, staying at the level of the upper vertebral end plate will lead the surgeon to the tip of the TP. From that point, dissection can be carried out as described above. This study examined the anatomy of the TP and defined the approach to expose the VA safely during anterior cervical spine exposure. Clin. Anat. 30:492-497, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Is Xpert MTB/RIF appropriate for diagnosing tuberculous pleurisy with pleural fluid samples? A systematic review.

PubMed

Huo, Zhen-Yu; Peng, Li

2018-06-25

Tuberculous pleurisy (TP) presents a diagnostic problem due to the limitations of traditional diagnostic methods. Different studies with the Xpert MTB/RIF assay have drawn variable conclusions about its values in TP diagnosis. We conducted a meta-analysis to assess whether the Xpert MTB/RIF assay is appropriate for the diagnosis of TP using pleural fluid samples. A systematic search of four literature databases in English and Chinese language was performed to identify studies involving the use of Xpert MTB/RIF in patients with TP confirmed by plural biopsy and/or mycobacterial culture. Pooled sensitivity, specificity and accordance proportion were calculated, and the forest plots were generated to assess the accuracy of Xpert MTB/RIF for TP diagnosis. We identified 23 studies meeting our inclusion criteria. The pooled sensitivity and specificity of Xpert MTB/RIF were 30% (95% CI: 21-42%, I 2  = 87.93%) and 99% (95% CI: 97-100%, I 2  = 96.20%), respectively, and the area under the SROC curve (AUC) of Xpert MTB/RIF was 0.86 (95% CI: 0.83-0.89). Compared with drug susceptibility testing (DST), the pooled accordance rate of Xpert MTB/RIF in detecting rifampicin-susceptible cases and rifampicin-resistant cases was 99% (95% CI: 95-104%, I 2  = 8.7%) and 94% (95% CI: 86-102%), respectively. Our analysis suggests that the Xpert MTB/RIF assay is of limited value as a screening test for TP but has a high potential for confirming TP diagnosis and differentiating TP from non-TB diseases using pleural fluid samples.

Flaxseed suppressed prostatic epithelial proliferation in a rat model of benign prostatic hyperplasia.

PubMed

Said, Mahmoud M; Hassan, Nahla S; Schlicht, Michael J; Bosland, Maarten C

2015-01-01

Benign prostatic hyperplasia (BPH), a disease occurring frequently among elderly males, is a slow progressive enlargement of the fibromuscular and epithelial structures of the prostate gland. Dietary factors may influence the prostate and exert an influence on prostatic growth and disease. The current study was undertaken to investigate the protective effect of dietary flaxseed supplementation against testosterone-induced prostatic hyperplasia in male rats. Forty male Wistar rats were divided into 5 groups: (1) untreated control; (2) treatment with testosterone propionate (TP) to induce prostate enlargement; (3) TP-treated group fed a diet containing 5% milled flaxseed; (4) TP-treated group fed a diet containing 10% milled flaxseed; and (5) TP-treated group fed a diet containing 20 ppm finasteride. Treatment with TP significantly increased the absolute and relative weights of different prostatic lobes, serum testosterone (T), and testosterone/estradiol ratio, as well as prostatic vascular endothelial growth factor (VEGF) expression, RNA synthesis per cell, and epithelial cell proliferation, detected as Ki67 labeling. Histopathological examination did not reveal marked differences in acinar morphology in ventral prostate, whereas morphometric analysis showed significantly increased epithelial cell height. Co-administration of flaxseed or finasteride with TP significantly reduced prostatic VEFG, epithelial cell proliferation, and RNA/DNA ratio, along with a significant increase in serum T and testosterone/estradiol ratio compared with TP-only-treated rats. Our results indicate that flaxseed, similar to the 5α-reductase inhibitor finasteride, blocked TP-induced prostate enlargement in a rat model of BPH, likely through suppression of prostatic VEFG and cellular proliferation.

Sensitive detection of Treponema pallidum DNA from the whole blood of patients with syphilis by the nested PCR assay.

PubMed

Wang, Cuini; Cheng, Yuanyuan; Liu, Biao; Wang, Yuanyuan; Gong, Weiming; Qian, Yihong; Guan, Zhifang; Lu, Haikong; Gu, Xin; Shi, Mei; Zhou, Pingyu

2018-05-09

The aim of this work was to investigate the application of the nested PCR assay for the detection of Treponema pallidum (TP) DNA from the blood of patients with different stages of syphilis. In this study, a nested PCR method targeting the Tpp47 and polA genes (Tpp47-Tp-PCR and polA-Tp-PCR) was developed to detect TP-DNA in whole blood samples collected from 262 patients with different stages of syphilis (84 primary syphilis, 97 secondary syphilis, and 81 latent syphilis patients). The PCR assay detected T. pallidum DNA in 53.6% and 62.9% of the patients with primary and secondary syphilis, respectively, which was much higher than the detection levels in patients with latent syphilis (7.4%) (both p < 0.001). For primary syphilis, a low RPR (0-16) was correlated with a higher detection rate of TP-DNA, whereas for secondary syphilis, the higher detection rate of blood TP-DNA was correlated with higher blood RPR titers (at or beyond 32). For latent syphilis, TP-DNA was only detectable by PCR in the early phase of the latent infection. Thus, blood RPR titers were correlated with the blood T. pallidum burden, but the correlations varied with primary and secondary syphilis. The results indicate that nested PCR is a sensitive method for detecting blood TP-DNA and is especially useful for detecting early syphilis including primary syphilis and secondary syphilis. The findings also suggest that the PCR assay may be used to complement other methods to enhance the diagnosis of syphilis.

Novel strategy for immunomodulation: Dissolving microneedle array encapsulating thymopentin fabricated by modified two-step molding technology.

PubMed

Lin, Shiqi; Cai, Bingzhen; Quan, Guilan; Peng, Tingting; Yao, Gangtao; Zhu, Chune; Wu, Qiaoli; Ran, Hao; Pan, Xin; Wu, Chuanbin

2018-01-01

Thymopentin (TP5) is commonly used in the treatment for autoimmune diseases, with a short plasma half-life (30s) and a long treatment period (7 days to 6 months). It is usually administrated by syringe injection, resulting in compromised patient compliance. Dissolving microneedle array (DMNA) offers a superior approach for transdermal delivery of biological macromolecules, as it allows painless penetration through the stratum corneum and generates minimal biohazardous waste after dissolving in the skin. Despite recent advances in DMNA as a novel approach for transdermal drug delivery, problem of insufficient mechanical strength remains to be solved. In this study, TP5-loaded DMNA (TP5-DMNA) was uniquely developed using a modified two-step molding technology. The higher mechanical strength was furnished by employing bovine serum albumin (BSA) as a co-material to fabricate the needles. The obtained TP5-DMNA containing BSA displayed better skin penetration and higher drug loading efficiency than that without BSA. The in vivo pharmacodynamics study demonstrated that TP5-DMNA had comparative effect on immunomodulation to intravenous injection of TP5, in terms of ameliorating the CD4+/CD8+ ratio, SOD activity and MDA value to the basal level. Only mild irritation was observed at the site of administration. These results suggest that the novel TP5-DMNA utilizing BSA provides an alternative approach for convenient and safe transdermal delivery of TP5, which is a promising administration strategy for future clinical application. Copyright © 2017 Elsevier B.V. All rights reserved.

Adversity, time, and well-being: A longitudinal analysis of time perspective in adulthood.

PubMed

Holman, E Alison; Silver, Roxane Cohen; Mogle, Jacqueline A; Scott, Stacey B

2016-09-01

Despite the prominence of time in influential aging theories and the ubiquity of stress across the life span, research addressing how time perspective (TP) and adversity are associated with well-being across adulthood is rare. Examining the role of TP in coping with life events over the life span would be best accomplished after large-scale population-based exposure to a specific event, with repeated assessments to examine within- and between-person differences over time. A national sample aged 18-91 years (N = 722, M = 49.4 years) was followed for 3 years after the September 11, 2001 (9/11) terrorist attacks. Respondents completed assessments of 9/11-related television (TV) exposure 9-21 days after the attacks, temporal disintegration 2 months post-9/11, and TP, ongoing stress, and well-being at 12, 24, and 36 months post-9/11. Results provided support for measurement invariance of TP across time and across age. Early 9/11-related TV exposure was significantly associated with greater temporal disintegration. Temporal disintegration and ongoing stress, in turn, were associated with between- and within-person variation in past TP. This effect was qualified by an age interaction that indicated a stronger relationship between ongoing stress and past TP for younger compared with older adults. Past and future TP were significantly and independently related to individual differences and within-person variation in psychological well-being, regardless of age. Future work should incorporate adversity as an important correlate of TP across adulthood. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Nonarticular tenderness and functional status in patients with diffuse idiopathic skeletal hyperostosis.

PubMed

Mader, Reuven; Novofastovski, Irina; Rosner, Ehud; Adawi, Muhammad; Herer, Paula; Buskila, Dan

2010-09-01

To investigate the degree of nonarticular tenderness and functional status in patients with diffuse idiopathic skeletal hyperostosis (DISH). We assessed these variables' correlation with their clinical, radiographic, and constitutional measurements and with metabolic syndrome (MS). Eighty-seven patients with DISH were compared with 65 controls without DISH. Examination of nonarticular tenderness was performed by thumb palpation. Tenderness was scored for the 18 fibromyalgia tender points (TP), and 4 control points. Nonarticular tenderness was expressed by the number of TP and by the total tenderness score (TTS). The Short Health Assessment Questionnaire (HAQ II) was administered to all participants. Clinical and laboratory data were collected from all patients. Patients were classified as having MS by both the National Cholesterol Education Program and World Health Organization definitions. There was a statistically significant difference in TTS between controls and patients with DISH. The mean tenderness of many individual TP was significantly higher in the DISH group compared with the control group. TP counts, TTS, and body mass index (BMI) positively correlated with the HAQ II. There was a linear trend in intensity of T-spine bony bridges (BB) and the total number of TP as well as many individual TP. Patients with DISH were more likely to be affected by MS. No correlation was found between TP count, TTS, and MS. Patients with DISH have a lower pain threshold than patients who do not have DISH. TP count and TTS correlate with the functional status, BMI, waist circumference, and high-grade BB. No correlation was observed between pain threshold and MS.

Modulation of gene expression by alpha-tocopherol and alpha-tocopheryl phosphate in thp-1 monocytes

USDA-ARS?s Scientific Manuscript database

The naturally occurring vitamin E analogue, alpha-tocopheryl phosphate (alphaTP), has been reported to be more potent than the un-phosphorylated alpha alpha-tocopherol (alphaT). We have now measured plasma levels of alphaTP and compared the cellular effects of alphaTP and gamma-tocopheryl phosphate ...

76 FR 59703 - Notice of Intent To Award Affordable Care Act (ACA) Funding, RFA-TP-08-001

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-27

... Intent To Award Affordable Care Act (ACA) Funding, RFA- TP-08-001 AGENCY: Centers for Disease Control and... of Intent to award Affordable Care Act (ACA) funding to Preparedness and Emergency Response Research... continuation application under Funding Opportunity Announcement RFA-TP- 08-001, ``Preparedness and Emergency...

Preparation of gelatin films incorporated with tea polyphenol nanoparticles for enhancing controlled-release antioxidant properties

USDA-ARS?s Scientific Manuscript database

Tea polyphenols (TP) were incorporated into edible gelatin films either alone or incorporated into nanoparticles in order to determine the physico-chemical properties of the film and the antioxidant properties of TP in a solid gelatin matrix. The TP containing nanoparticles were prepared by cross-li...

Bioinformatic dissecting of TP53 regulation pathway underlying butyrate-induced histone modification in epigenetic regulation

USDA-ARS?s Scientific Manuscript database

Butyrate affects cell proliferation, differentiation and motility. Butyrate inhibits histone deacetylase (HDAC) activities and induces cell cycle arrest and apoptosis. TP53 is one of the most active upstream regulators discovered by IPA in our RNA sequencing data set. The TP53 signaling pathway pl...

Development status of LE-7 fuel turbopump

NASA Astrophysics Data System (ADS)

Nakano, T.; Nagao, R.; Ohta, T.; Warashina, S.; Watanabe, H.; Oguchi, H.

The liquid hydrogen turbopump (LH2 T/P) for the LE-7 engine has been developed since 1984. The component PDR was held in June 1988 and the basic troubles occurred at the development test were solved. Next, the component CDR-1 was held in December 1989 in order to feed back the test results of prototype LH2 T/P model to the design of qualification phase T/P. So, the production of these turbopumps was admitted. Recently, the component CDR-2 was held in February 1992 to reflect the counterparts adopted for some troubles (impeller and turbine blade cracks and so on) in long-time engine tests to the design of qualification phase T/P. In the qualification phase, the hydraulic characteristics and strength in the engine operating range were examined at the LH2 T/P component test, and its endurance confirmed at the engine tests. The LH2 turbopump component test was held at NASDA Kakuda and the engine test at Tashiro and Tanegashima. This paper describes the development status of LH2 T/P, containing the design description and the content of some troubles and its counterplans.

Trace Element Determination and Cardioprotection of Terminalia pallida Fruit Ethanolic Extract in Isoproterenol Induced Myocardial Infarcted Rats by ICP-MS.

PubMed

Althaf Hussain, Shaik; Kareem, Mohammed Abdul; Rasool, Shaik Nayab; Al Omar, Suliman Yousef; Saleh, Alwasel; Al-Fwuaires, Manal Abdulrahman; Daddam, Jayasimha Rayalu; Devi, Kodidhela Lakshmi

2018-01-01

The trace elements and minerals in Terminalia pallida fruit ethanolic extract (TpFE) were determined by the instrument inductively coupled plasma-mass spectrometry (ICP-MS), and the cardioprotection of TpFE against isoproterenol (ISO)-administered rats was studied. Rats were pretreated with TpFE (100, 300, and 500 mg/kg bw) for 30 days, with concurrent administration of ISO (85 mg/kg bw) for two consecutive days. The levels of trace elements and minerals in TpFE were below the permitted limits of World Health Organization standards. ISO administration significantly increased the heart weight and cardiac marker enzymes in serum, xanthine oxidase, sodium, and calcium in the heart, whereas significantly decreased body weight, reduced glutathione, glutathione-S-transferase, superoxide dismutase, and potassium in the heart. Oral pretreatment of TpFE significantly prevented the ISO-induced alterations. This is the first report that revealed the determination of trace elements and mineral nutrients of TpFE by ICP-MS which plays a principal role in the herbal drug discovery for the treatment of cardiovascular diseases.

Solid-state thermal behavior and stability studies of theophylline-citric acid cocrystals prepared by neat cogrinding or thermal treatment

NASA Astrophysics Data System (ADS)

Hsu, Po-Chun; Lin, Hong-Liang; Wang, Shun-Li; Lin, Shan-Yang

2012-08-01

To investigate the thermal behavior of cocrystal formed between anhydrous theophylline (TP) and anhydrous citric acid (CA) by neat manual cogrinding or thermal treatment, DSC and FTIR microspectroscopy with curve-fitting analysis were applied. The physical mixture and 60-min ground mixture were stored at 55±0.5 °C/40±2% RH condition to determine their stability behavior. Typical TP-CA cocrystals were prepared by slow solvent evaporation method. Results indicate that the cogrinding process could gradually induce the cocrystal formation between TP and CA. The IR spectral peak shift from 3495 to 3512 cm-1 and the stepwise appearance of several new IR peaks at 1731, 1712, 1676, 1651, 1557 and 1265 cm-1 with cogrinding time suggest that the mechanism of TP-CA cocrystal formation was evidenced by interacting TP with CA through the intermolecular O-H···O hydrogen bonding. The stability of 60-min ground mixture of TP-CA was confirmed at 55±0.5 °C/40±2% RH condition over a storage time of 60 days.

Thymidine phosphorylase exerts complex effects on bone resorption and formation in myeloma

PubMed Central

Liu, Huan; Liu, Zhiqiang; Du, Juan; He, Jin; Lin, Pei; Amini, Behrang; Starbuck, Michael W.; Novane, Nora; Shah, Jatin J.; Davis, Richard E.; Hou, Jian; Gagel, Robert F.; Yang, Jing

2016-01-01

Myelomatous bone disease is characterized by the development of lytic bone lesions and a concomitant reduction in bone formation, leading to chronic bone pain and fractures. To understand the underlying mechanism, we investigated the contribution of myeloma-expressed thymidine phosphorylase (TP) to bone lesions. In osteoblast progenitors, TP upregulated the methylation of RUNX2 and osterix, leading to decreased bone formation. In osteoclast progenitors, TP upregulated the methylation of IRF8, thereby enhanced expression of NFATc1, leading to increased bone resorption. TP reversibly catalyzes thymidine into thymine and 2DDR. Myeloma-secreted 2DDR bound to integrin αVβ3/α5β1 in the progenitors, activated PI3K/Akt signaling, and increased DNMT3A expression, resulting in hypermethylation of RUNX2, osterix, and IRF8. This study elucidates an important mechanism for myeloma-induced bone lesions, suggesting that targeting TP may be a viable approach to healing resorbed bone in patients. As TP overexpression is common in bone-metastatic tumors, our findings could have additional mechanistic implications. PMID:27559096

Performance Analysis of TCP Enhancements in Satellite Data Networks

NASA Technical Reports Server (NTRS)

Broyles, Ren H.

1999-01-01

This research examines two proposed enhancements to the well-known Transport Control Protocol (TCP) in the presence of noisy communication links. The Multiple Pipes protocol is an application-level adaptation of the standard TCP protocol, where several TCP links cooperate to transfer data. The Space Communication Protocol Standard - Transport Protocol (SCPS-TP) modifies TCP to optimize performance in a satellite environment. While SCPS-TP has inherent advantages that allow it to deliver data more rapidly than Multiple Pipes, the protocol, when optimized for operation in a high-error environment, is not compatible with legacy TCP systems, and requires changes to the TCP specification. This investigation determines the level of improvement offered by SCPS-TP's Corruption Mode, which will help determine if migration to the protocol is appropriate in different environments. As the percentage of corrupted packets approaches 5 %, Multiple Pipes can take over five times longer than SCPS-TP to deliver data. At high error rates, SCPS-TP's advantage is primarily caused by Multiple Pipes' use of congestion control algorithms. The lack of congestion control, however, limits the systems in which SCPS-TP can be effectively used.

Development of Software Sensors for Determining Total Phosphorus and Total Nitrogen in Waters

PubMed Central

Lee, Eunhyoung; Han, Sanghoon; Kim, Hyunook

2013-01-01

Total nitrogen (TN) and total phosphorus (TP) concentrations are important parameters to assess the quality of water bodies and are used as criteria to regulate the water quality of the effluent from a wastewater treatment plant (WWTP) in Korea. Therefore, continuous monitoring of TN and TP using in situ instruments is conducted nationwide in Korea. However, most in situ instruments in the market are expensive and require a time-consuming sample pretreatment step, which hinders the widespread use of in situ TN and TP monitoring. In this study, therefore, software sensors based on multiple-regression with a few easily in situ measurable water quality parameters were applied to estimate the TN and TP concentrations in a stream, a lake, combined sewer overflows (CSOs), and WWTP effluent. In general, the developed software sensors predicted TN and TP concentrations of the WWTP effluent and CSOs reasonably well. However, they showed relatively lower predictability for TN and TP concentrations of stream and lake waters, possibly because the water quality of stream and lake waters is more variable than that of WWTP effluent or CSOs. PMID:23307350

[The study of tongue pressure during swallowing liquid in healthy adults].

PubMed

Li, Qiang; Minagi, Yoshitomo; Hori, Kazuhiro; Fujiwara, Shigehiro; Ono, Takahiro; Chen, Yongjin

2015-03-01

To investigate the tongue pressure (TP) produced by tongue-hard palate contact in the process of normally swallowing liquid in healthy adults. Thirteen adult male subjects were recruited to perform a single swallow of 5 ml water when sitting with upright position. The tongue pressure sensor sheet was used to monitor TP as a result of tongue-hard palate approximatation in the anteriomedian, midmedian, posteriomedian and circumferential parts, and the swallowing sound was recorded by microphone. The temporal sequence of TP at each measured part was obtained after setting the swallowing sound as the reference time. Also, the total duration, pre-peak duration, post-peak duration, maximum magnitude and integrated value of TP were recorded and compared among the measured parts. TP was produced from anterior to posterior along the midline of hard palate during normal swallowing of water [Ch1: (-0.40 ± 0.22) s, Ch2: (-0.36 ± 0.21) s, Ch3: (-0.24 ± 0.18) s], with the circumferential TP [Ch4: (-0.38 ± 0.23) s, Ch5: (-0.40 ± 0.23) s] occurring nearly to the anteriomedian one (P > 0.05). Before the swallowing sound (P < 0.05), TP at each part reached a peak synchronously [Ch1: (-0.12 ± 0.24) s, Ch2: (-0.16 ± 0.22) s, Ch3: (-0.13 ± 0.21) s, Ch4: (-0.16 ± 0.23) s, Ch5: (-0.17 ± 0.23) s] in a rapid manner (P > 0.05), then decreased gradually until disappeared simultaneously [Ch1: (0.32 ± 0.23) s, Ch2: (0.27 ± 0.21) s, Ch3: (0.23 ± 0.16) s, Ch4: (0.33 ± 0.31) s, Ch5: (0.33 ± 0.29) s] (P > 0.05) after the swallowing sound (P < 0.05). The TP related parameters (the total duration of TP:Ch1: (0.72 ± 0.20) s, Ch2: (0.63 ± 0.16) s, Ch3: (0.47 ± 0.17) s, Ch4: (0.70 ± 0.35) s, Ch5: (0.73 ± 0.29) s; the pre-peak duration of TP: Ch1: (0.28 ± 0.21) s, Ch2: (0.20 ± 0.16) s, Ch3: (0.12 ± 0.10) s, Ch4: (0.21 ± 0.22) s, Ch5: (0.23 ± 0.21) s; the post-peak duration of TP: Ch1: (0.44 ± 0.23) s, Ch2: (0.43 ± 0.18) s, Ch3: (0.36 ± 0.18) s, Ch4: (0.49 ± 0.25) s, Ch5: (0.50 ± 0.23) s; the maximum magnitude of TP: Ch1: (13.80 ± 7.73) kPa, Ch2: (12.40 ± 6.51) kPa, Ch3: (10.26 ± 7.15) kPa, Ch4: (12.16 ± 5.38) kPa, Ch5: (13.08 ± 5.05) kPa; the integrated value of TP: Ch1: (4.99 ± 3.69) kPa×s, Ch2: (4.25 ± 2.13) kPa×s, Ch3: (2.88 ± 1.87) kPa×s, Ch4: (4.32 ± 3.47) kPa×s, Ch5: (4.63 ± 2.49) kPa×s were significantly smaller in the posteriomedian part among all the five parts measured. No laterality was found in TP produced at the circumferential parts of the hard palate (P > 0.05). The TP at each part coordinates precisely during swallowing. The effective measurement of TP by tongue pressure sensor sheet will facilitate the evaluation of oral swallowing and the diagnosis of dysphagia simply and non-invasively.

Regulation of Lipid and Glucose Metabolism by Phosphatidylcholine Transfer Protein

PubMed Central

Kang, Hye Won; Wei, Jie; Cohen, David E.

2010-01-01

Phosphatidylcholine transfer protein (PC-TP, a.k.a. StARD2) binds phosphatidylcholines and catalyzes their intermembrane transfer and exchange in vitro. The structure of PC-TP comprises a hydrophobic pocket and a well-defined head-group binding site, and its gene expression is regulated by peroxisome proliferator activated receptor α. Recent studies have revealed key regulatory roles for PC-TP in lipid and glucose metabolism. Notably, Pctp−/− mice are sensitized to insulin action and exhibit more efficient brown fat-mediated thermogenesis. PC-TP appears to limit access of fatty acids to mitochondria by stimulating the activity of thioesterase superfamily member 2, a newly characterized long-chain fatty acyl-CoA thioesterase. Because PC-TP discriminates among phosphatidylcholines within lipid bilayers, it may function as a sensor that links metabolic regulation to membrane composition. PMID:20338778

Inhibition of glycogen synthase kinase 3beta ameliorates triptolide-induced acute cardiac injury by desensitizing mitochondrial permeability transition

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

Wang, Wenwen; Yang, Yanqin; Xiong, Zhewen

Triptolide (TP), a diterpene triepoxide, is a major active component of Tripterygium wilfordii extracts, which are prepared as tablets and has been used clinically for the treatment of inflammation and autoimmune disorders. However, TP's therapeutic potential is limited by severe adverse effects. In a previous study, we reported that TP induced mitochondria dependent apoptosis in cardiomyocytes. Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine kinase that plays important roles in the necrosis and apoptosis of cardiomyocytes. Our study aimed to investigate the role of GSK-3β in TP-induced cardiotoxicity. Inhibition of GSK-3β activity by SB 216763, a potent and selective GSK-3more » inhibitor, prominently ameliorated the detrimental effects in C57BL/6J mice with TP administration, which was associated with a correction of GSK-3β overactivity. Consistently, in TP-treated H9c2 cells, SB 216763 treatment counteracted GSK-3β overactivity, improved cell viability, and prevented apoptosis by modulating the expression of Bcl-2 family proteins. Mechanistically, GSK-3β interacted with and phosphorylated cyclophilin F (Cyp-F), a key regulator of mitochondrial permeability transition pore (mPTP). GSK-3β inhibition prevented the phosphorylation and activation of Cyp-F, and desensitized mPTP. Our findings suggest that pharmacological targeting of GSK-3β could represent a promising therapeutic strategy for protecting against cardiotoxicity induced by TP. - Highlights: • GSK-3β inhibition ameliorates TP-induced cardiotoxicity in vitro and in vivo. • GSK-3β controls Cyp-F activation, and regulates mPTP and apoptosis in H9c2 cells. • The protective effect is attributed to GSK-3β activity rather than to protein level. • GSK-3β may be a promising target against TP-induced cardiotoxicity.« less

Acute Tears of the Tibialis Posterior Tendon Following Ankle Sprain.

PubMed

Jackson, Lyle T; Dunaway, Linda J; Lundeen, Gregory A

2017-07-01

Traumatic tears of the tibialis posterior (TP) tendon following an ankle sprain are rare. The purpose of this study was to report our case series of TP tendon tears following an ankle sprain. Patients with persistent TP tendon pain after an ankle sprain were retrospectively identified over a 4-year period and reviewed. A comparison of magnetic resonance imaging (MRI) interpretations by a radiologist and surgeon was made. Patients failing conservative management underwent operative repair of the TP tendon tear and concomitant pathology. Failure of the index surgery was defined as TP tendinosis, which was treated with excision and flexor digitorum longus tendon transfer. Outcomes were measured with the Foot Function Index (FFI) and American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot scores. Thirteen patients were found to have a TP tendon tear following an ankle sprain. The incidence for TP tears with sprains presented to our clinic was 1.04%. MRI identified TP tendon pathology in 4 patients by a radiologist review and in 11 patients by a surgeon review. The most common concomitant pathology was a talar osteochondral defect in 13 of 13 patients and ligament instability in 12 of 13 patients (5/13 lateral, 3/13 medial, 4/13 multidirectional instability). Four of 13 patients failed the index surgery. Of the 9 remaining patients, 4 had clinical follow-up at an average of 4.6 years postoperatively. The average FFI subscale scores were the following: pain, 40.4; disability, 28.9; and activity, 23.6. The average AOFAS hindfoot score was 68.8. Despite being rare, a TP tendon tear should be included in the differential diagnosis for persistent medial-sided pain following an ankle sprain. MRI findings can be subtle. Associated pathology was very common and likely confounded the diagnosis and outcomes. Patients should be counseled on the possibility of poor outcomes and long-term pain. Level IV, case series.

Changes in Tibetan Plateau latitude as an important factor for understanding East Asian climate since the Eocene: A modeling study

NASA Astrophysics Data System (ADS)

Zhang, Ran; Jiang, Dabang; Ramstein, Gilles; Zhang, Zhongshi; Lippert, Peter C.; Yu, Entao

2018-02-01

Previous climate modeling studies suggest that the surface uplift of the Himalaya-Tibetan plateau (TP) is a crucial parameter for the onset and intensification of the East Asian monsoon during the Cenozoic. Most of these studies have only considered the Himalaya-TP in its present location between ∼26°N and ∼40°N despite numerous recent geophysical studies that reconstruct the Himalaya-TP 10° or more of latitude to the south during the early Paleogene. We have designed a series of climate simulations to explore the sensitivity of East Asian climate to the latitude of the Himalaya-TP. Our simulations suggest that the East Asian climate strongly depends on the latitude of the Himalaya-TP. Surface uplift of a proto-Himalaya-TP in the subtropics intensifies aridity throughout inland Asia north of ∼40°N and enhances precipitation over East Asia. In contrast, the rise of a proto-Himalaya-TP in the tropics only slightly intensifies aridity in inland Asia north of ∼40°N, and slightly increases precipitation in East Asia. Importantly, this climate sensitivity to the latitudinal position of the Himalaya-TP is non-linear, particularly for precipitation across East Asia. The simulated precipitation patterns across East Asia are significantly different between our scenarios in which a proto-plateau is situated between ∼11°N and ∼25°N and between ∼20°N and ∼33°N, but they are similar when the plateau translates northward from between ∼20°N and ∼33°N to its modern position. Our simulations, when interpreted in the context of climate proxy data from Central Asia, support geophysically-based paleogeographic reconstructions in which the southern margin of a modern-elevation proto-Himalaya-TP was located at ∼20°N or further north in the Eocene.

[1,2,4]Triazolo[1,5-a]pyridine as Building Blocks for Universal Host Materials for High-Performance Red, Green, Blue and White Phosphorescent Organic Light-Emitting Devices.

PubMed

Song, Wenxuan; Shi, Lijiang; Gao, Lei; Hu, Peijun; Mu, Haichuan; Xia, Zhenyuan; Huang, Jinhai; Su, Jianhua

2018-02-14

The electron-accepting [1,2,4]triazolo[1,5-a]pyridine (TP) moiety was introduced to build bipolar host materials for the first time, and two host materials based on this TP acceptor and carbazole donor, namely, 9,9'-(2-([1,2,4]triazolo[1,5-a]pyridin-2-yl)-1,3-phenylene)bis(9H-carbazole) (o-CzTP) and 9,9'-(5-([1,2,4]triazolo[1,5-a]pyridin-2-yl)-1,3-phenylene)bis(9H-carbazole) (m-CzTP), were designed and synthesized. These two TP-based host materials possess a high triplet energy (>2.9 eV) and appropriate highest occupied molecular orbital/lowest unoccupied molecular orbital levels as well as the bipolar transporting feature, which permits their applicability as universal host materials in multicolor phosphorescent organic light-emitting devices (PhOLEDs). Blue, green, and red PhOLEDs based on o-CzTP and m-CzTP with the same device configuration all show high efficiencies and low efficiency roll-off. The devices hosted by o-CzTP exhibit maximum external quantum efficiencies (η ext ) of 27.1, 25.0, and 15.8% for blue, green, and red light emitting, respectively, which are comparable with the best electroluminescene performance reported for FIrpic-based blue, Ir(ppy) 3 -based green, and Ir(pq) 2 (acac)-based red PhOLEDs equipped with a single-component host. The white PhOLEDs based on the o-CzTP host and three lumophors containing red, green, and blue emitting layers were fabricated with the same device structure, which exhibit a maximum current efficiency and η c of 40.4 cd/A and 17.8%, respectively, with the color rendering index value of 75.

Clinicopathological features and clinical outcomes associated with TP53 and BRAFNon-V600 mutations in cutaneous melanoma patients.

PubMed

Kim, Dae Won; Haydu, Lauren E; Joon, Aron Y; Bassett, Roland L; Siroy, Alan E; Tetzlaff, Michael T; Routbort, Mark J; Amaria, Rodabe N; Wargo, Jennifer A; McQuade, Jennifer L; Kemnade, Jan; Hwu, Patrick; Woodman, Scott E; Roszik, Jason; Kim, Kevin B; Gershenwald, Jeffrey E; Lazar, Alexander J; Davies, Michael A

2017-04-15

BRAF V600 , NRAS, TP53, and BRAF Non-V600 are among the most common mutations detected in non-acral cutaneous melanoma patients. Although several studies have identified clinical and pathological features associated with BRAF V600 and NRAS mutations, limited data are available regarding the correlates and significance of TP53 and BRAF Non-V600 mutations. This study analyzed the patient demographics, primary tumor features, and clinical outcomes of a large cohort of non-acral cutaneous melanoma patients who had undergone clinically indicated molecular testing (n = 926). The prevalence of BRAF V600 , NRAS, TP53, and BRAF Non-V600 mutations was 43%, 21%, 19%, and 7%, respectively. The presence of a TP53 mutation was associated with older age (P = .019), a head and neck primary tumor site (P = .0001), and longer overall survival (OS) from the diagnosis of stage IV disease in univariate (P = .039) and multivariate analyses (P = .015). BRAF Non-V600 mutations were associated with older age (P = .005) but not with primary tumor features or OS from stage IV. Neither TP53 nor BRAF Non-V600 mutations correlated significantly with OS with frontline ipilimumab treatment, and the TP53 status was not significantly associated with outcomes with frontline BRAF inhibitor therapy. Eleven patients with BRAF Non-V600 mutations were treated with a BRAF inhibitor. Three patients were not evaluable for a response because of treatment cessation for toxicities; the remaining patients had disease progression as the best response to therapy. These results add to the understanding of the clinical features associated with TP53 and BRAF Non-V600 mutations in advanced cutaneous melanoma patients, and they support the rationale for evaluating the prognostic significance of TP53 in other cohorts of melanoma patients. Cancer 2017;123:1372-1381. © 2016 American Cancer Society. © 2016 American Cancer Society.

Interaction of prostanoid EP3 and TP receptors in guinea-pig isolated aorta: contractile self-synergism of 11-deoxy-16,16-dimethyl PGE2

PubMed Central

Jones, RL; Woodward, DF

2011-01-01

BACKGROUND AND PURPOSE Surprisingly high contractile activity was reported for 11-deoxy-16,16-dimethyl prostaglandin E2 (DX-DM PGE2) on pig cerebral artery when used as a selective EP3 receptor agonist. This study investigated the selectivity profile of DX-DM PGE2, focusing on the interaction between its EP3 and TP (thromboxane A2-like) agonist activities. EXPERIMENTAL APPROACH Contraction of guinea-pig trachea (EP1 system) and aorta (EP3 and TP systems) was measured in conventional organ baths. KEY RESULTS Strong contraction of guinea-pig aorta to sulprostone and 17-phenyl PGE2 (EP3 agonists) was only seen under priming with a second contractile agent such as phenylephrine, histamine or U-46619 (TP agonist). In contrast, DX-DM PGE2 induced strong contraction, which on the basis of treatment with (DG)-3ap (EP3 antagonist) and/or BMS-180291 (TP antagonist) was attributed to self-synergism arising from co-activation of EP3 and TP receptors. EP3/TP self-synergism also accounted for contraction induced by PGF2α and its analogues (+)-cloprostenol and latanoprost-FA. DX-DM PGE2 also showed significant EP1 agonism on guinea-pig trachea as defined by the EP1 antagonists SC-51322, (ONO)-5-methyl-1 and AH-6809, although AH-6809 exhibited poor specificity at concentrations ≥3 µM. CONCLUSIONS AND IMPLICATIONS EP3/TP self-synergism, as seen with PGE/PGF analogues in this study, may confound EP3 agonist potency comparisons and the characterization of prostanoid receptor systems. The competitive profile of a TP antagonist may be distorted by variation in the silent/overt contraction profile of the EP3 system in different studies. The relevance of self-synergism to in vivo actions of natural prostanoid receptor agonists is discussed. PMID:20955363

Cloud vertical structure, precipitation, and cloud radiative effects over Tibetan Plateau

NASA Astrophysics Data System (ADS)

Liu, Y.; Yan, Y.; Lu, J.

2017-12-01

The vertical structure of clouds and its connection with precipitation and cloud radiative effects (CRE) over the Tibetan Plateau (TP) are analyzed and compared with its neighboring land and tropical oceans based on CloudSat and Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) products and the Tropical Rainfall Measuring Mission (TRMM) precipitation data. Unique characteristics of cloud vertical structure and CRE over the TP are found. The cloud amount shows seasonal variation over the TP, which presents a single peak (located in 7-11 km) during January to April and two peaks (located in 5-8 km and 11-17 km separately) after mid-June, and then resumes to one peak (located in 5-10 km) after mid-August. Topography-induced restriction on moisture supply leads to a compression effect on clouds, i.e., the reduction in both cloud thickness and number of cloud layers, over the TP. The topography-induced compression effect is also shown in the range in the variation of cloud thickness and cloud-top height corresponding to different precipitation intensity, which is much smaller over the TP than its neighboring regions. In summer, cloud ice particles over the TP are mostly located at lower altitude (5-10 km) with richer variety of sizes and aggregation in no rain conditions compared to other regions. Ice water content becomes abundant and the number concentration tends to be dense at higher levels when precipitation is enhanced. The longwave CRE in the atmosphere over the TP is a net cooling effect. The vertical structure of CRE over the TP is unique compared to other regions: there exists a strong cooling layer of net CRE at the altitude of 8 km, from June to the beginning of October; the net radiative heating layer above the surface is shallower but stronger underneath 7 km and with a stronger seasonal variation over the TP.

Effect of decreasing dietary phosphorus supply on net recycling of inorganic phosphate in lactating dairy cows.

PubMed

Puggaard, L; Kristensen, N B; Sehested, J

2011-03-01

Five ruminally cannulated lactating Holstein cows, fitted with permanent indwelling catheters in the mesenteric vein, hepatic vein, portal vein, and an artery were used to study intestinal absorption and net recycling of inorganic phosphate (P(i)) to the gastrointestinal tract. Treatments were low P (LP; 2.4 g of P/kg of DM) and high P (HP; 3.4 g of P/kg of DM). The dietary total P (tP) concentrations were obtained by replacing 0.50% calcium carbonate in the LP diet with 0.50% monocalcium phosphate in the HP diet. Diets were fed for 14 d and cows were sampled on d 14 in each period. Cows were fed restrictively, resulting in equal dry matter intakes as well as milk, fat, and protein yields between treatments. Net P(i) recycling (primarily salivary) was estimated as the difference between net portal plasma flux (net absorption of P(i)) and apparently digested tP (feed - fecal tP difference). Phosphorus intake, apparently digested tP, and fecal tP excretion decreased with LP. An effect of decreased tP intake on net portal plasma flux of P(i) could not be detected. However, despite numerically minute net fluxes across the liver, the net splanchnic flux of P(i) was less in LP compared with that in HP. Though arterial plasma P(i) concentration decreased, net P(i) recycling was not decreased when tP intake was decreased, and recycling of P(i) was maintained at the expense of deposition of P(i) in bones. Data are not consistent with salivary P(i) secretion being the primary regulator of P(i) homeostasis at low tP intakes. On the contrary, maintaining salivary P(i) recycling at low tP intakes indicates that rumen function was prioritized at the expense of bone P reserves. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Clinical implications of genomic profiles in metastatic breast cancer with a focus on TP53 and PIK3CA, the most frequently mutated genes.

PubMed

Kim, Ji-Yeon; Lee, Eunjin; Park, Kyunghee; Park, Woong-Yang; Jung, Hae Hyun; Ahn, Jin Seok; Im, Young-Hyuck; Park, Yeon Hee

2017-04-25

Breast cancer (BC) has been genetically profiled through large-scale genome analyses. However, the role and clinical implications of genetic alterations in metastatic BC (MBC) have not been evaluated. Therefore, we conducted whole-exome sequencing (WES) and RNA-Seq of 37 MBC samples and targeted deep sequencing of another 29 MBCs. We evaluated somatic mutations from WES and targeted sequencing and assessed gene expression and performed pathway analysis from RNA-Seq. In this analysis, PIK3CA was the most commonly mutated gene in estrogen receptor (ER)-positive BC, while in ER-negative BC, TP53 was the most commonly mutated gene (p = 0.018 and p < 0.001, respectively). TP53 stopgain/loss and frameshift mutation was related to low expression of TP53 in contrast nonsynonymous mutation was related to high expression. The impact of TP53 mutation on clinical outcome varied with regard to ER status. In ER-positive BCs, wild type TP53 had a better prognosis than mutated TP53 (median overall survival (OS) (wild type vs. mutated): 88.5 ± 54.4 vs. 32.6 ± 10.7 (months), p = 0.002). In contrast, mutated TP53 had a protective effect in ER-negative BCs (median OS: 0.10 vs. 32.6 ± 8.2, p = 0.026). However, PIK3CA mutation did not affect patient survival. In gene expression analysis, CALM1, a potential regulator of AKT, was highly expressed in PIK3CA-mutated BCs. In conclusion, mutation of TP53 was associated with expression status and affect clinical outcome according to ER status in MBC. Although mutation of PIK3CA was not related to survival in this study, mutation of PIK3CA altered the expression of other genes and pathways including CALM1 and may be a potential predictive marker of PI3K inhibitor effectiveness.

Two Theileria parva CD8 T Cell Antigen Genes Are More Variable in Buffalo than Cattle Parasites, but Differ in Pattern of Sequence Diversity

PubMed Central

Pelle, Roger; Graham, Simon P.; Njahira, Moses N.; Osaso, Julius; Saya, Rosemary M.; Odongo, David O.; Toye, Philip G.; Spooner, Paul R.; Musoke, Anthony J.; Mwangi, Duncan M.; Taracha, Evans L. N.; Morrison, W. Ivan; Weir, William; Silva, Joana C.; Bishop, Richard P.

2011-01-01

Background Theileria parva causes an acute fatal disease in cattle, but infections are asymptomatic in the African buffalo (Syncerus caffer). Cattle can be immunized against the parasite by infection and treatment, but immunity is partially strain specific. Available data indicate that CD8+ T lymphocyte responses mediate protection and, recently, several parasite antigens recognised by CD8+ T cells have been identified. This study set out to determine the nature and extent of polymorphism in two of these antigens, Tp1 and Tp2, which contain defined CD8+ T-cell epitopes, and to analyse the sequences for evidence of selection. Methodology/Principal Findings Partial sequencing of the Tp1 gene and the full-length Tp2 gene from 82 T. parva isolates revealed extensive polymorphism in both antigens, including the epitope-containing regions. Single nucleotide polymorphisms were detected at 51 positions (∼12%) in Tp1 and in 320 positions (∼61%) in Tp2. Together with two short indels in Tp1, these resulted in 30 and 42 protein variants of Tp1 and Tp2, respectively. Although evidence of positive selection was found for multiple amino acid residues, there was no preferential involvement of T cell epitope residues. Overall, the extent of diversity was much greater in T. parva isolates originating from buffalo than in isolates known to be transmissible among cattle. Conclusions/Significance The results indicate that T. parva parasites maintained in cattle represent a subset of the overall T. parva population, which has become adapted for tick transmission between cattle. The absence of obvious enrichment for positively selected amino acid residues within defined epitopes indicates either that diversity is not predominantly driven by selection exerted by host T cells, or that such selection is not detectable by the methods employed due to unidentified epitopes elsewhere in the antigens. Further functional studies are required to address this latter point. PMID:21559495

Two Theileria parva CD8 T cell antigen genes are more variable in buffalo than cattle parasites, but differ in pattern of sequence diversity.

PubMed

Pelle, Roger; Graham, Simon P; Njahira, Moses N; Osaso, Julius; Saya, Rosemary M; Odongo, David O; Toye, Philip G; Spooner, Paul R; Musoke, Anthony J; Mwangi, Duncan M; Taracha, Evans L N; Morrison, W Ivan; Weir, William; Silva, Joana C; Bishop, Richard P

2011-04-29

Theileria parva causes an acute fatal disease in cattle, but infections are asymptomatic in the African buffalo (Syncerus caffer). Cattle can be immunized against the parasite by infection and treatment, but immunity is partially strain specific. Available data indicate that CD8(+) T lymphocyte responses mediate protection and, recently, several parasite antigens recognised by CD8(+) T cells have been identified. This study set out to determine the nature and extent of polymorphism in two of these antigens, Tp1 and Tp2, which contain defined CD8(+) T-cell epitopes, and to analyse the sequences for evidence of selection. Partial sequencing of the Tp1 gene and the full-length Tp2 gene from 82 T. parva isolates revealed extensive polymorphism in both antigens, including the epitope-containing regions. Single nucleotide polymorphisms were detected at 51 positions (∼12%) in Tp1 and in 320 positions (∼61%) in Tp2. Together with two short indels in Tp1, these resulted in 30 and 42 protein variants of Tp1 and Tp2, respectively. Although evidence of positive selection was found for multiple amino acid residues, there was no preferential involvement of T cell epitope residues. Overall, the extent of diversity was much greater in T. parva isolates originating from buffalo than in isolates known to be transmissible among cattle. The results indicate that T. parva parasites maintained in cattle represent a subset of the overall T. parva population, which has become adapted for tick transmission between cattle. The absence of obvious enrichment for positively selected amino acid residues within defined epitopes indicates either that diversity is not predominantly driven by selection exerted by host T cells, or that such selection is not detectable by the methods employed due to unidentified epitopes elsewhere in the antigens. Further functional studies are required to address this latter point.

Discharge Patterns of Human Tensor Palatini Motor Units During Sleep Onset

PubMed Central

Nicholas, Christian L.; Jordan, Amy S.; Heckel, Leila; Worsnop, Christopher; Bei, Bei; Saboisky, Julian P.; Eckert, Danny J.; White, David P.; Malhotra, Atul; Trinder, John

2012-01-01

Study Objectives: Upper airway muscles such as genioglossus (GG) and tensor palatini (TP) reduce activity at sleep onset. In GG reduced muscle activity is primarily due to inspiratory modulated motor units becoming silent, suggesting reduced respiratory pattern generator (RPG) output. However, unlike GG, TP shows minimal respiratory modulation and presumably has few inspiratory modulated motor units and minimal input from the RPG. Thus, we investigated the mechanism by which TP reduces activity at sleep onset. Design: The activity of TP motor units were studied during relaxed wakefulness and over the transition from wakefulness to sleep. Setting: Sleep laboratory. Participants: Nine young (21.4 ± 3.4 years) males were studied on a total of 11 nights. Intervention: Sleep onset. Measurements and Results: Two TP EMGs (thin, hooked wire electrodes), and sleep and respiratory measures were recorded. One hundred twenty-one sleep onsets were identified (13.4 ± 7.2/subject), resulting in 128 motor units (14.3 ± 13.0/subject); 29% of units were tonic, 43% inspiratory modulated (inspiratory phasic 18%, inspiratory tonic 25%), and 28% expiratory modulated (expiratory phasic 21%, expiratory tonic 7%). There was a reduction in both expiratory and inspiratory modulated units, but not tonic units, at sleep onset. Reduced TP activity was almost entirely due to de-recruitment. Conclusions: TP showed a similar distribution of motor units as other airway muscles. However, a greater proportion of expiratory modulated motor units were active in TP and these expiratory units, along with inspiratory units, tended to become silent over sleep onset. The data suggest that both expiratory and inspiratory drive components from the RPG are reduced at sleep onset in TP. Citation: Nicholas CL; Jordan AS; Heckel L; Worsnop C; Bei B: Saboisky JP; Eckert DJ; White DP; Malhotra A; Trinder J. Discharge patterns of human tensor palatini motor units during sleep onset. SLEEP 2012;35(5):699-707. PMID:22547896

Composite Adrenocortical Carcinoma and Neuroblastoma in an Infant With a TP53 Germline Mutation: A Case Report and Literature Review.

PubMed

Tang, Yue-Jia; Yu, Ting-Ting; Ma, Jing; Zhou, Ying; Xu, Min; Gao, Yi-Jin

2018-05-09

Li-Fraumeni syndrome is a kind of hereditary cancer predisposition syndromes, and is caused by TP53 gene mutation. Adrenocortical carcinoma (ACC) is commonly described as the most closely related tumor with this disease. Here, we present a case of a male infant with composite ACC and neuroblastoma who inherited a TP53 gene mutation from his mother, a 20-year-old carrier without any tumor to date. This TP53 gene mutation may be pathogenic and lead to composite malignancies of ACC and neuroblastoma.

Expected orbit determination performance for the TOPEX/Poseidon mission

NASA Technical Reports Server (NTRS)

Nerem, R. S.; Putney, Barbara H.; Marshall, J. A.; Lerch, Francis J.; Pavlis, Erricos C.; Klosko, Steven M.; Luthcke, Scott B.; Patel, Girish B.; Williamson, Ronald G.; Zelensky, Nikita P.

1993-01-01

Each of the components required for the computation of precise orbits for the TOPEX/Poseidon (T/P) spacecraft - gravity field modeling, nonconservative force modeling, and satellite tracking technologies - is examined. The research conducted in the Space Geodesy Branch at Goddard Space Flight Center in preparation for meeting the 13-cm radial orbit accuracy requirement for the T/P mission is outlined. New developments in modeling the earth's gravitational field and modeling the complex nonconservative forces acting on T/P are highlighted. The T/P error budget is reviewed, and a prelaunch assessment of the predicted orbit determination accuracies is summarized.

Temporal changes in nitrogen and phosphorus concentrations with comparisons to conservation practices and agricultural activities in the Lower Grand River, Missouri and Iowa, and selected watersheds, 1969–2015

USGS Publications Warehouse

Krempa, Heather M.; Flickinger, Allison K.

2017-08-01

This report presents the results of a cooperative study by the U.S. Geological Survey and Missouri Department of Natural Resources to estimate total nitrogen (TN) and total phosphorus (TP) concentrations at monitoring sites within and near the Lower Grand River hydrological unit. The primary objectives of the study were to quantify temporal changes in TN and TP concentrations and compare those concentrations to conservation practices and agricultural activities. Despite increases in funding during 2011–15 for conservation practices in the Lower Grand River from the Mississippi River Basin Healthy Watersheds Initiative, decreases in flow-normalized TN and TP concentrations during this time at the long-term Grand River site were less than at other long-term sites, which did not receive funding from the Mississippi River Basin Healthy Watersheds Initiative. The relative differences in the magnitude of flow-normalized TN and TP concentrations among long-term sites are directly related to the amount of agricultural land use within the watershed. Significant relations were determined between nitrogen from cattle manure and flow-normalized TN concentrations at selected long-term sites, indicating livestock manure may be a substantial source of nitrogen within the selected long-term site watersheds. Relations between flow-normalized TN and TP concentrations with Conservation Reserve Program acres and with nitrogen and phosphorus from commercial fertilizer indicate that changes in these factors alone did not have a substantial effect on stream TN and TP concentrations; other landscape activities, runoff, within-bank nutrients that are suspended during higher streamflows, or a combination of these have had a greater effect on stream TN and TP concentrations; or there is a lag time that is obscuring relations. Temporal changes in flow-adjusted TN and TP concentrations were not substantial at Lower Grand River Mississippi River Basin Healthy Watersheds Initiative sites, indicating factors besides stream variability did not have substantial effects on TN and TP concentrations. Flow-weighted TN and TP concentrations at Lower Grand River Mississippi River Basin Healthy Watershed Initiative sites increase with increasing streamflow, which indicates runoff, within-bank nutrients that are suspended during higher streamflows, or both, have more effect on stream TN and TP concentrations than consistent point sources or groundwater sources. Timing of TN and TP concentration increases compared to streamflow increases indicate that nitrogen and phosphorus loads are more strongly related to streamflow than to a particular period of the year, indicating that runoff, within-bank nutrients that are suspended during higher streamflows, or both are a substantial source of nutrients regardless of timing.

Clinical, Histologic, and Molecular Analysis of Differences Between Erythematotelangiectatic Rosacea and Telangiectatic Photoaging.

PubMed

Helfrich, Yolanda R; Maier, Lisa E; Cui, Yilei; Fisher, Gary J; Chubb, Heather; Fligiel, Suzanne; Sachs, Dana; Varani, James; Voorhees, John

2015-08-01

Facial erythema and telangiectasia are commonly associated with the erythematotelangiectatic subtype of rosacea (ETR). It is important for clinicians to recognize that these findings can also be associated with a subtype of photoaging, which we term telangiectatic photoaging (TP). To demonstrate that ETR and TP are distinct dermatologic disorders. A case-control observational study comparing clinical, histologic, and gene expression features of 26 participants with ETR, 20 with TP, and 11 age- and sex-matched controls in the Program for Clinical Research in Dermatology at University of Michigan. Findings of clinical history and examination, light and electron microscopy, immunohistochemical analyses, and real-time quantitative reverse-transcriptase polymerase chain reaction gene expression. Transient erythema was greater in the ETR group (38% graded moderate to severe) than in the TP (0%; P < .001) and control groups (0%; P = .002). Nontransient erythema was also greater in the ETR group (50% graded moderate to severe) than in the TP (25%; P = .03) and control groups (0%; P < .001). Participants with ETR tended to have erythema and telangiectasia primarily on the central face (79%), whereas those with TP tended to have more lateral involvement (57%; P < .001). Those with ETR had significantly less clinical evidence of photodamage (0% graded 6-8 on a photonumeric scale) than those with TP (40% graded 6-8; P = .01). Histologically, there was less evidence of photodamage in ETR than in TP, which had wispy collagen and solar elastosis surrounding blood vessels. Immunohistologic analysis demonstrated greater geometric mean immunostained area by mast cell tryptase staining in ETR samples (0.018%) than in TP (0.004%; P = .01) or control samples (0.001%; P < .001) but no increase in mast cell number, indicative of greater mast cell degranulation. Gene expression of matrix metalloproteinase-3 was 4-fold greater in ETR samples than in TP samples (P = .004) and 5-fold higher than in control samples (P = .004). Gene expression of the neuropeptides calcitonin gene-related peptide (CGRP-α) and substance P was significantly increased in ETR compared with TP (9-fold [P < .001] and 5-fold [P = .002], respectively) and control samples (10-fold [P < .001] and 28-fold [P < .001], respectively). Telangiectatic photoaging is characterized by less transient and nontransient erythema, a more lateral distribution of erythema and telangiectasia, less neurogenic mast cell activation, and less MMP-mediated matrix remodeling than ETR. These data demonstrate that TP is a distinct clinical entity from ETR that can be distinguished on the basis of clinical, histologic, and gene expression findings.

Efficacy of the antimicrobial peptide TP4 against Helicobacter pylori infection: in vitro membrane perturbation via micellization and in vivo suppression of host immune responses in a mouse model

PubMed Central

Narayana, Jayaram Lakshmaiah; Huang, Han-Ning; Wu, Chang-Jer; Chen, Jyh-Yih

2015-01-01

Helicobacter pylori infection is marked by a strong association with various gastric diseases, including gastritis, ulcers, and gastric cancer. Antibiotic treatment regimens have low success rates due to the rapid occurrence of resistant H. pylori strains, necessitating the development of novel anti-H. pylori strategies. Here, we investigated the therapeutic potential of a novel peptide, Tilapia Piscidin 4 (TP4), against multidrug resistant gastric pathogen H. pylori, based on its in vitro and in vivo efficacy. TP4 inhibited the growth of both antibiotic-sensitive and -resistant H. pylori (CagA+, VacA+) via membrane micelle formation, which led to membrane depolarization and extravasation of cellular constituents. During colonization of gastric tissue, H. pylori infection maintains high T regulatorysubsets and a low Th17/Treg ratio, and results in expression of both pro- and anti-inflammatory cytokines. Treatment with TP4 suppressed Treg subset populations and pro- and anti-inflammatory cytokines. TP4 restored the Th17/Treg balance, which resulted in early clearance of H. pylori density and recovery of gastric morphology. Toxicity studies demonstrated that TP4 treatment has no adverse effects in mice or rabbits. The results of this study indicate that TP4 may be an effective and safe monotherapeutic agent for the treatment of multidrug resistant H. pylori infections. PMID:26002554

In vitro antioxidant and in vivo photoprotective effect of pistachio (Pistacia vera L., variety Bronte) seed and skin extracts.

PubMed

Martorana, Maria; Arcoraci, Teresita; Rizza, Luisa; Cristani, Mariateresa; Bonina, Francesco Paolo; Saija, Antonina; Trombetta, Domenico; Tomaino, Antonio

2013-03-01

Pistachio (Pistacia vera L.) nuts are a rich source of phenolic compounds, known for their high antioxidant activity, and contained not only in the seeds but also in the skin. A pistachio cultivar of high quality is typical of Bronte, Sicily, Italy. The purpose of our study was to investigate the chemical composition and antioxidant properties of two polyphenol-rich extracts from skins (TP) and decorticated seeds (SP) of Bronte pistachios, and to verify the potential use of these extracts for topical photoprotective products. Chemical analysis showed that the TP and SP extracts contain high levels of phenolic compounds, but the TP extract is about ten times richer in phenols than the SP extract, being anthocyanins the most abundant compounds found in the TP extract. Both these extracts, and especially the TP extract, possess good radical scavenger/antioxidant properties, as shown in a series of in vitro assays carried out using homogenous and non-homogenous chemical environment. Furthermore both the TP extract and, although at a lower degree, the SP extract reduce, when topically applied, UV-B-induced skin erythema in human volunteers. These findings suggest that extracts from Bronte TP and SP could be successfully employed as photoprotective ingredients in topical cosmetic and pharmaceutical formulations. Copyright © 2013 Elsevier B.V. All rights reserved.

Analysis of non-point and point source pollution in China: case study in Shima Watershed in Guangdong Province

NASA Astrophysics Data System (ADS)

Fang, Huaiyang; Lu, Qingshui; Gao, Zhiqiang; Shi, Runhe; Gao, Wei

2013-09-01

China economy has been rapidly increased since 1978. Rapid economic growth led to fast growth of fertilizer and pesticide consumption. A significant portion of fertilizers and pesticides entered the water and caused water quality degradation. At the same time, rapid economic growth also caused more and more point source pollution discharge into the water. Eutrophication has become a major threat to the water bodies. Worsening environment problems forced governments to take measures to control water pollution. We extracted land cover from Landsat TM images; calculated point source pollution with export coefficient method; then SWAT model was run to simulate non-point source pollution. We found that the annual TP loads from industry pollution into rivers are 115.0 t in the entire watershed. Average annual TP loads from each sub-basin ranged from 0 to 189.4 ton. Higher TP loads of each basin from livestock and human living mainly occurs in the areas where they are far from large towns or cities and the TP loads from industry are relatively low. Mean annual TP loads that delivered to the streams was 246.4 tons and the highest TP loads occurred in north part of this area, and the lowest TP loads is mainly distributed in middle part. Therefore, point source pollution has much high proportion in this area and governments should take measures to control point source pollution.

ThinPrep versus conventional smear cytologic preparations in the analysis of thyroid fine-needle aspiration specimens.

PubMed

Biscotti, C V; Hollow, J A; Toddy, S M; Easley, K A

1995-08-01

Paired fine-needle aspiration specimens were analyzed from 41 surgically resected thyroid nodules, to compare diagnostic accuracy, amount (absent, mild, moderate, or marked) and pattern (diffuse, droplets, or both) of colloid, nuclear detail (poor, satisfactory, or excellent) and cytoplasmic detail (intact or disrupted) in ThinPrep (TP) (Cytyc, Marlborough, MA) versus conventional smear (CS) cytologic preparations. The 41 surgical specimens included 25 colloid nodules, 6 papillary carcinomas, 4 follicular adenomas, 2 minimally invasive (encapsulated) follicular carcinomas, 3 Hashimoto's thyroiditis, and 1 Grave's disease. Both techniques identified seven of the eight carcinomas with the minimally invasive follicular carcinomas categorized as hypercellular follicular nodule, possibly malignant (HCFN). One papillary carcinoma was classified as a HCFN by both TP and CS techniques. The four follicular adenomas were classified as HCFN based on the TP slides. One oxyphilic follicular adenoma, associated with focal lymphocytic thyroiditis, was misinterpreted as Hashimoto's thyroiditis on a conventional smear. Three colloid nodules were interpreted as HCFN based on the TP slides. Two of these were similarly classified based on the conventional smear. ThinPrep slides contained less colloid and the colloid occurred as droplets rather than a diffuse pattern. TP slides had better nuclear detail but more often disrupted cytoplasm. In conclusion, the TP process does alter some cellular features; however, we experienced similar diagnostic accuracy with the TP and conventional smear preparations.

Phytometabolite Dehydroleucodine Induces Cell Cycle Arrest, Apoptosis, and DNA Damage in Human Astrocytoma Cells through p73/p53 Regulation.

PubMed

Bailon-Moscoso, Natalia; González-Arévalo, Gabriela; Velásquez-Rojas, Gabriela; Malagon, Omar; Vidari, Giovanni; Zentella-Dehesa, Alejandro; Ratovitski, Edward A; Ostrosky-Wegman, Patricia

2015-01-01

Accumulating evidence supports the idea that secondary metabolites obtained from medicinal plants (phytometabolites) may be important contributors in the development of new chemotherapeutic agents to reduce the occurrence or recurrence of cancer. Our study focused on Dehydroleucodine (DhL), a sesquiterpene found in the provinces of Loja and Zamora-Chinchipe. In this study, we showed that DhL displayed cytostatic and cytotoxic activities on the human cerebral astrocytoma D384 cell line. With lactone isolated from Gynoxys verrucosa Wedd, a medicinal plant from Ecuador, we found that DhL induced cell death in D384 cells by triggering cell cycle arrest and inducing apoptosis and DNA damage. We further found that the cell death resulted in the increased expression of CDKN1A and BAX proteins. A marked induction of the levels of total TP73 and phosphorylated TP53, TP73, and γ-H2AX proteins was observed in D384 cells exposed to DhL, but no increase in total TP53 levels was detected. Overall these studies demonstrated the marked effect of DhL on the diminished survival of human astrocytoma cells through the induced expression of TP73 and phosphorylation of TP73 and TP53, suggesting their key roles in the tumor cell response to DhL treatment.

Phytometabolite Dehydroleucodine Induces Cell Cycle Arrest, Apoptosis, and DNA Damage in Human Astrocytoma Cells through p73/p53 Regulation

PubMed Central

Bailon-Moscoso, Natalia; González-Arévalo, Gabriela; Velásquez-Rojas, Gabriela; Malagon, Omar; Vidari, Giovanni; Zentella-Dehesa, Alejandro; Ratovitski, Edward A.; Ostrosky-Wegman, Patricia

2015-01-01

Accumulating evidence supports the idea that secondary metabolites obtained from medicinal plants (phytometabolites) may be important contributors in the development of new chemotherapeutic agents to reduce the occurrence or recurrence of cancer. Our study focused on Dehydroleucodine (DhL), a sesquiterpene found in the provinces of Loja and Zamora-Chinchipe. In this study, we showed that DhL displayed cytostatic and cytotoxic activities on the human cerebral astrocytoma D384 cell line. With lactone isolated from Gynoxys verrucosa Wedd, a medicinal plant from Ecuador, we found that DhL induced cell death in D384 cells by triggering cell cycle arrest and inducing apoptosis and DNA damage. We further found that the cell death resulted in the increased expression of CDKN1A and BAX proteins. A marked induction of the levels of total TP73 and phosphorylated TP53, TP73, and γ-H2AX proteins was observed in D384 cells exposed to DhL, but no increase in total TP53 levels was detected. Overall these studies demonstrated the marked effect of DhL on the diminished survival of human astrocytoma cells through the induced expression of TP73 and phosphorylation of TP73 and TP53, suggesting their key roles in the tumor cell response to DhL treatment. PMID:26309132

Benzo[a]pyrene, Aflatoxine B1 and Acetaldehyde Mutational Patterns in TP53 Gene Using a Functional Assay: Relevance to Human Cancer Aetiology

PubMed Central

Paget, Vincent; Lechevrel, Mathilde; André, Véronique; Le Goff, Jérémie; Pottier, Didier; Billet, Sylvain; Garçon, Guillaume; Shirali, Pirouz; Sichel, François

2012-01-01

Mutations in the TP53 gene are the most common alterations in human tumours. TP53 mutational patterns have sometimes been linked to carcinogen exposure. In hepatocellular carcinoma, a specific G>T transversion on codon 249 is classically described as a fingerprint of aflatoxin B1 exposure. Likewise G>T transversions in codons 157 and 158 have been related to tobacco exposure in human lung cancers. However, controversies remain about the interpretation of TP53 mutational pattern in tumours as the fingerprint of genotoxin exposure. By using a functional assay, the Functional Analysis of Separated Alleles in Yeast (FASAY), the present study depicts the mutational pattern of TP53 in normal human fibroblasts after in vitro exposure to well-known carcinogens: benzo[a]pyrene, aflatoxin B1 and acetaldehyde. These in vitro patterns of mutations were then compared to those found in human tumours by using the IARC database of TP53 mutations. The results show that the TP53 mutational patterns found in human tumours can be only partly ascribed to genotoxin exposure. A complex interplay between the functional impact of the mutations on p53 phenotype and the cancer natural history may affect these patterns. However, our results strongly support that genotoxins exposure plays a major role in the aetiology of the considered cancers. PMID:22319594

BM-520, an original TXA2 modulator, inhibits the action of thromboxane A2 and 8-iso-prostaglandin F2alphain vitro and in vivo on human and rodent platelets, and aortic vascular smooth muscles from rodents.

PubMed

Rolin, S; Hanson, J; Vastersaegher, C; Cherdon, C; Pratico, D; Masereel, B; Dogne, J M

2007-08-01

Thromboxane A(2) (TXA(2)) and 8-iso-PGF(2alpha) are two prostanoid agonists of the thromboxane A(2) receptor (TP), whose activation has been involved in platelet aggregation and atherosclerosis. Agents able to counteract the actions of these agonists are of great interest in the treatment and prevention of cardiovascular events. Here, we investigated in vitro and in vivo the pharmacological profile of BM-520, a new TP antagonist. In our experiments, this compound showed a great binding affinity for human washed platelets TP receptors, and prevented human platelet activation and aggregation induced by U-46619, arachidonic acid and 8-iso-PGF(2alpha). The TP receptor antagonist property of BM-520 was confirmed by its relaxing effect on rat aorta smooth muscle preparations precontracted with U-46619 and 8-iso-PGF(2alpha). Further, its TP antagonism was also demonstrated in vivo in guinea pig after a single intravenous injection (10 mg kg(-1)). We conclude that this novel TP antagonist could be a promising therapeutic tool in pathologies such as atherosclerosis where an increased production of TXA(2) and 8-iso-PGF(2alpha), as well as TP activation are well-established pathogenic events.

Theme and Thematic Progression in English Writing Teaching

ERIC Educational Resources Information Center

Jing, Wei

2015-01-01

Theme and thematic progression (T/TP) is a major aspect of the way that speakers construct their messages in a way which makes them fit smoothly into the unfolding language event. While studies have illustrated the usefulness of observing T/TP to identify English learners' writing difficulties and suggested that T/TP should be included in English…

Framing the Teaching Philosophy Statement for Health Educators: What It Includes and How It Can Inform Professional Development

ERIC Educational Resources Information Center

Ratnapradipa, Dhitinut; Abrams, Thereasa

2012-01-01

Teaching philosophy (TP) statements are increasingly required within academia for hiring and promotion purposes. For health educators, a TP can be a valuable resource for academicians as well as practitioners, linking educational theory with teaching techniques, philosophy with practice. The process of formulating a TP statement provides the…

Attenuation of dermal wounds via downregulating oxidative stress and inflammatory markers by protocatechuic acid rich n-butanol fraction of Trianthema portulacastrum Linn. in wistar albino rats.

PubMed

Yadav, Ekta; Singh, Deepika; Yadav, Pankajkumar; Verma, Amita

2017-12-01

Oxidative stress and inflammation contribute as a key factor for retarding the process of dermal wound healing. Trianthema portulcastrum Linn. (TP) leaves reported to possess antioxidant, antifungal, anti-inflammatory and antibacterial properties, which could make TP a promising wound healing agent. The current study was aimed to estimate the antioxidant potential of the fractionated hydroethanolic extract of TP leaves and evaluate wound healing activity by excision and incision wound models along with the assessment of possible underlying mechanism. Ethyl acetate, chloroform and n-butanol fractions of the hydroethanolic extract of TP leaves were examined for in vitro antioxidant ability by DPPH method. Strongest antioxidant activity bearing n-butanol fraction (nBuTP) was further analyzed quantitatively by High Performance Liquid Chromatography coupled with Diode Array Detector (HPLC-DAD). Wound healing potential of nBUTP using excision and incision wound model was studied. Wistar albino rats were randomly divided into four groups, containing six animals in each group; group I served as control treated with simple ointment base, group II was standard group, treated with povidone-iodine ointment USP (5%), group III treated with nBuTP 5% w/w ointment, and group IV treated with nBuTP 10%w/w ointment. All the groups were topically applied their respective ointments, once daily, till the complete healing achieved. Wound healing was assessed by analyzing % wound closure, hydroxyproline content, epithelialization period, tensile strength, enzymatic antioxidative status and inflammatory markers. Total phenolic and flavonoid content of the extract was estimated to be 112.32±1.12 and 84.42±0.47mg/g, respectively. HPLC-DAD of nBuTP confirmed the presence of chlorogenic acid (20.74±0.03), protocatechuic acid (34.45±0.02mg/g), caffeic acid (4.31±0.03mg/g) and ferulic acid (1.43±0.01mg/g). 5% and 10%w/w nBuTP ointment significantly accelerated the wound healing process dose-dependently in both wound models, evidenced by the faster rate of wound contraction, epithelialization, increased hydroxyproline content, high tensile strength, increased antioxidant enzyme activity, decreased the level of inflammatory markers compared to the control group. Histopathological studies also revealed the dose-dependant amelioration of wound healing by re-epithelialization, collagenation and vascularization of wounded skin sample in nBuTP treated groups. These results implicate potential medicinal value of nBuTP to heal dermal wounds. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Improved oral absorption and anti-lung cancer activity of paclitaxel-loaded mixed micelles.

PubMed

Hou, Jian; Sun, E; Zhang, Zhen-Hai; Wang, Jing; Yang, Lei; Cui, Li; Ke, Zhong-Cheng; Tan, Xiao-Bin; Jia, Xiao-Bin; Lv, Huixia

2017-11-01

The aim of this study was to establish a paclitaxel (PTX)-loaded mixed micelle delivery system (PTX-TP-M) with vitamin E-TPGS (TPGS) and Plasdone®S-630 Copovidone (PVPS630) as carriers to improve the solubility, oral absorption, and anti-tumor activity of PTX against lung cancer. In this study, PTX-TP-M was prepared using the ethanol thin-film dispersion method followed by characterization of the binary mixed micelles system. The average size of the PTX-TP-M was 83.5 ± 1.8 nm with a polydispersity index of 0.265 ± 0.007 and the drug loading (DL%) and entrapment efficiency (EE%) were 3.09 ± 0.09% and 95.67 ± 2.84%, respectively, which contributed to a high solubility of PTX about 24947-fold increase in water (4.78 ± 0.14 mg/mL). In addition, TEM analysis showed that the PTX-TP-M appeared spherical in structure and was well dispersed without aggregation and adhesion. In vitro release studies showed that the PTX-TP-M displayed a sustained release compared to free PTX in the dialysis bag. The efflux ratio of PTX reduced from 44.83 to 3.52 when formulated as PTX-TP-M; a 92.15% reduction, studied using the Caco-2 monolayer model. The oral bioavailability of PTX also improved by 4.35-fold, suggesting that PTX-TP-M can markedly promote the absorption in the gastrointestinal tract. Using in vitro MTT assays, it was observed that cytotoxicity was markedly increased, and IC 50 values of PTX-TP-M (3.14 ± 0.85 and 8.28 ± 1.02 μg/mL) were lower than those of PTX solution (5.21 ± 0.93 and 14.53 ± 1.96 μg/mL) in A549 and Lewis cell, respectively. In vivo anti-tumor studies showed that PTX-TP-M achieved higher anti-tumor efficacy compared with PTX in Lewis bared C57BL/6 mice. Furthermore, a gastrointestinal safety assay also proved the safety of PTX-TP-M. All results demonstrated that the PTX-TP-M exhibited great potential for delivering PTX with increased solubility, oral bioavailability, and anti-cancer activity and this binary mixed micelles drug delivery system has potential to be used clinically.

Long-term trends of phosphorus concentrations in an artificial lake: Socio-economic and climate drivers.

PubMed

Vystavna, Yuliya; Hejzlar, Josef; Kopáček, Jiří

2017-01-01

European freshwater ecosystems have undergone significant human-induced and environmentally-driven variations in nutrient export from catchments throughout the past five decades, mainly in connection with changes in land-use, agricultural practice, waste water production and treatment, and climatic conditions. We analysed the relations among concentration of total phosphorus (TP) in the Slapy Reservoir (a middle reservoir of the Vltava River Cascade, Czechia), and socio-economic and climatic factors from 1963 to 2015. The study was based on a time series analysis, using conventional statistical tools, and the identification of breaking points, using a segmented regression. Results indicated clear long-term trends and seasonal patterns of TP, with annual average TP increasing up until 1991 and decreasing from 1992 to 2015. Trends in annual, winter and spring average TP concentrations reflected a shift in development of sewerage and sanitary infrastructure, agricultural application of fertilizers, and livestock production in the early 1990s that was associated with changes from the planned to the market economy. No trends were observed for average TP in autumn. The summer average TP has fluctuated with increased amplitude since 1991 in connection with recent climate warming, changes in thermal stratification stability, increased water flow irregularities, and short-circuiting of TP-rich inflow during high flow events. The climate-change-induced processes confound the generally declining trend in lake-water TP concentration and can result in eutrophication despite decreased phosphorus loads from the catchment. Our findings indicate the need of further reduction of phosphorus sources to meet ecological quality standards of the EU Water Framework Directive because the climate change may lead to a greater susceptibility of the aquatic ecosystem to the supply of nutrients.

Evaluation of the Recombinant Protein TpF1 of Treponema pallidum for Serodiagnosis of Syphilis

PubMed Central

Jiang, Chuanhao; Zhao, Feijun; Xiao, Jinhong; Zeng, Tiebing; Yu, Jian; Ma, Xiaohua; Wu, Haiying

2013-01-01

Syphilis is a chronic infection caused by Treponema pallidum subsp. pallidum, and diagnosis with sensitive and specific methods is a challenging process that is important for its prevention and treatment. In the present study, we established a recombinant protein TpF1-based indirect immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and a Western blot assay for human and rabbit sera. The 20-kDa recombinant protein TpF1 was detected by Western blotting performed with sera from rabbits immunized with recombinant TpF1 and infected with the T. pallidum Nichols strain and T. pallidum clinical isolates but was not detected by Western blotting with sera from uninfected rabbits. The sensitivity of the recombinant protein was determined by screening sera from individuals with primary, secondary, latent, and congenital syphilis (n = 82). The specificity of the recombinant protein was determined by screening sera from uninfected controls (n = 30) and individuals with potentially cross-reactive infections, including Lyme disease (n = 30) and leptospirosis (n = 5). The sensitivities of TpF1-based ELISAs were 93.3%, 100%, 100%, and 100% for primary, secondary, latent, and congenital syphilis, respectively, and the specificities were all 100% for sera from uninfected controls and individuals with potentially cross-reactive infections. In Western blot assays, the sensitivities and specificities of TpF1 for human sera were all 100%. The reactivities of TpF1 with syphilitic sera were proportional to the titers of the T. pallidum particle agglutination (TPPA) assay. These data indicate that the recombinant protein TpF1 is a highly immunogenic protein in human and rabbit infections and a promising marker for the screening of syphilis. PMID:23945159

Bayesian network for point and diffuse source phosphorus transfer from dairy pastures in South otago, new zealand.

PubMed

Lucci, Gina M; Nash, David; McDowell, Richard W; Condron, Leo M

2014-07-01

Many factors affect the magnitude of nutrient losses from dairy farm systems. Bayesian Networks (BNs) are an alternative to conventional modeling that can evaluate complex multifactor problems using forward and backward reasoning. A BN of annual total phosphorus (TP) exports was developed for a hypothetical dairy farm in the south Otago region of New Zealand and was used to investigate and integrate the effects of different management options under contrasting rainfall and drainage regimes. Published literature was consulted to quantify the relationships that underpin the BN, with preference given to data and relationships derived from the Otago region. In its default state, the BN estimated loads of 0.34 ± 0.42 kg TP ha for overland flow and 0.30 ± 0.19 kg TP ha for subsurface flow, which are in line with reported TP losses in overland flow (0-1.1 kg TP ha) and in drainage (0.15-2.2 kg TP ha). Site attributes that cannot be managed, like annual rainfall and the average slope of the farm, were found to affect the loads of TP lost from dairy farms. The greatest loads (13.4 kg TP ha) were predicted to occur with above-average annual rainfall (970 mm), where irrigation of farm dairy effluent was managed poorly, and where Olsen P concentrations were above pasture requirements (60 mg kg). Most of this loading was attributed to contributions from overland flow. This study demonstrates the value of using a BN to understand the complex interactions between site variables affecting P loss and their relative importance. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Results of a program to control phosphorus discharges from dairy operations in south-central Florida, USA

NASA Astrophysics Data System (ADS)

Havens, Karl E.; Flaig, Eric G.; James, R. Thomas; Lostal, Sergio; Muszick, Dera

1996-07-01

During 1987 1992, a mandatory program to control phosphorus discharges was implemented at dairy operations located to the north of Lake Okeechobee, Florida, USA. Thirty of 48 dairies participated in this program and implemented best management practices (BMPs), which included the construction of intensive animal waste management systems. Eighteen dairies closed their milkproducing operations under a government-funded buyout program. In this paper, we compare trends in runoff total phosphorus (TP) concentrations among the dairies that remained active and implemented BMPs. A central feature of the dairy waste management system is the high intensity area (HIA), defined as the milking barn and adjacent vegetation-free land, encircled by a drainage ditch and dike. Animal waste from the HIA is diverted into anaerobic lagoons and storage ponds, from which water is periodically removed and used for irrigation of field crops. The impacts of BMP construction on runoff TP concentrations were immediate and, in most cases, dramatic. Average TP concentrations declined significantly ( P < 0.001), from 9.0 to 1.2 mg TP liter-1 at dairies in one basin (Lower Kissimmee River), and from 2.6 to 1.0 mg TP liter-1 in another (Taylor Creek/Nubbin Slough). Some sites experienced greater declines in TP than others. To elucidate possible causes for the difference in response, a multivariate statistical model was utilized. Independent variables included soil pH, soil drainage characteristics, spodic horizon depth, and the areas of different BMP components (pasture, HIA, spray fields). The analysis significantly separated dairies with the highest and lowest runoff TP concentrations. Lowest TP occurred at dairies having particular soil characteristic (shallow spodic horizon) and certain BMP features (large HIA and small heard pastures).

Transcription of TP0126, Treponema pallidum Putative OmpW Homolog, Is Regulated by the Length of a Homopolymeric Guanosine Repeat

PubMed Central

Brandt, Stephanie L.; Ke, Wujian; Reid, Tara B.; Molini, Barbara J.; Iverson-Cabral, Stefanie; Ciccarese, Giulia; Drago, Francesco; Lukehart, Sheila A.; Centurion-Lara, Arturo

2015-01-01

An effective mechanism for introduction of phenotypic diversity within a bacterial population exploits changes in the length of repetitive DNA elements located within gene promoters. This phenomenon, known as phase variation, causes rapid activation or silencing of gene expression and fosters bacterial adaptation to new or changing environments. Phase variation often occurs in surface-exposed proteins, and in Treponema pallidum subsp. pallidum, the syphilis agent, it was reported to affect transcription of three putative outer membrane protein (OMP)-encoding genes. When the T. pallidum subsp. pallidum Nichols strain genome was initially annotated, the TP0126 open reading frame was predicted to include a poly(G) tract and did not appear to have a predicted signal sequence that might suggest the possibility of its being an OMP. Here we show that the initial annotation was incorrect, that this poly(G) is instead located within the TP0126 promoter, and that it varies in length in vivo during experimental syphilis. Additionally, we show that TP0126 transcription is affected by changes in the poly(G) length consistent with regulation by phase variation. In silico analysis of the TP0126 open reading frame based on the experimentally identified transcriptional start site shortens this hypothetical protein by 69 amino acids, reveals a predicted cleavable signal peptide, and suggests structural homology with the OmpW family of porins. Circular dichroism of recombinant TP0126 supports structural homology to OmpW. Together with the evidence that TP0126 is fully conserved among T. pallidum subspecies and strains, these data suggest an important role for TP0126 in T. pallidum biology and syphilis pathogenesis. PMID:25802057

Sensitivity of plankton indices to lake trophic conditions.

PubMed

Ochocka, A; Pasztaleniec, A

2016-11-01

Herein, we report the response of indices based on phytoplankton and zooplankton and their combination to different nutrient concentrations in lakes. The study was carried out in ten lakes in northeastern Poland. Integrated samples were collected from the epilimnion during the summer of 2012-2013. Secchi disk visibility (SD), total phosphorus (TP), total nitrogen (TN), and chlorophyll a were used as proxies for eutrophication. We calculated 16 plankton indices: two phytoplankton indices, six crustacean indices, five rotiferan indices, two zooplankton diversity indices, and one combined phytoplankton and zooplankton index. Among them, nine indices with the strongest correlations with TP were selected: percentage share of Crustacean species indicative of high trophy in the indicative group's numbers (IHT CRU ), percentage share of Rotifera species indicative of high trophy in the indicative group's numbers IHT ROT , Crustacean ratio of biomass to numbers B/N CRU , phytoplankton trophic index (TI TP+TN ), Margalef's index, percentage share of cyclopoid biomass in total biomass of Crustacea (CB), Rotifera numbers (N ROT ), biomass of Cyclopoida (B CY ), and ratio of the cyclopoid biomass to the biomass of Cladocera (CY/CL). The sensitivity of the normalized values of these indices to proxies of eutrophication was tested. IHT CRU , IHT ROT , and B/N CRU were the most sensitive and gave the strongest responses at lower TP concentrations (<35 μg/L). The phytoplankton trophic index, TI TP+TN , together with the zooplankton-based Margalef's index and CB were very sensitive in both low (<35 μg/L) and high (>60 μg/L) TP conditions. On the other hand, N ROT , B CY , and CY/CL were slightly sensitive at low TP concentrations while their reaction was notable at high TP concentrations. A similar pattern of response was observed for TN concentration and SD visibility.

Vanillic acid attenuates testosterone-induced benign prostatic hyperplasia in rats and inhibits proliferation of prostatic epithelial cells.

PubMed

Jung, Yunu; Park, Jinbong; Kim, Hye-Lin; Youn, Dong-Hyun; Kang, JongWook; Lim, Seona; Jeong, Mi-Young; Sethi, Gautam; Park, Sung-Joo; Ahn, Kwang Seok; Um, Jae-Young

2017-10-20

Benign prostatic hyperplasia (BPH) is a common disease in the male population, especially in elderly men. Vanillic acid (VA), a dihydroxybenzoic derivative used as a flavoring agent, is reported to have an anti-inflammatory effect. However, there are no reports of its effects on BPH to date. BPH was induced with a pre-4-week treatment of daily subcutaneous injections of testosterone propionate (TP), and the normal control group received injections of ethanol with corn oil instead. Six weeks of further injections were done with (a) ethanol with corn oil, (b) TP only, (c) TP + finasteride, and (d) TP + VA. Finasteride was used as a positive control group. VA had protective effects on the TP-induced BPH. In the VA treatment group, the prostate weight was reduced, and the histological changes including the epithelial thickness and lumen area were restored like in the normal control group. Furthermore, in the VA treatment group, two proliferation related factors, high molecular weight cytokeratin 34βE12 and α smooth muscle actin, were significantly down-regulated compared to the TP-induced BPH group. The expressions of dihydrotestosterone and 5α-reductase, the most crucial factors in BPH development, were suppressed by VA treatment. Expressions of the androgen receptor, estrogen receptor α and steroid receptor coactivator 1 were also significantly inhibited by VA compared to the TP-induced BPH group. In addition, we established an in vitro model for BPH by treating a normal human prostatic epithelial cell line RWPE-1 with TP. VA successfully inhibited proliferation and BPH-related factors in a concentration-dependent manner in this newly established model. These results suggest a new and potential pharmaceutical therapy of VA in the treatment of BPH.

Baseline results from the UK SIGNIFY study: a whole-body MRI screening study in TP53 mutation carriers and matched controls.

PubMed

Saya, Sibel; Killick, Emma; Thomas, Sarah; Taylor, Natalie; Bancroft, Elizabeth K; Rothwell, Jeanette; Benafif, Sarah; Dias, Alexander; Mikropoulos, Christos; Pope, Jenny; Chamberlain, Anthony; Gunapala, Ranga; Izatt, Louise; Side, Lucy; Walker, Lisa; Tomkins, Susan; Cook, Jackie; Barwell, Julian; Wiles, Vicki; Limb, Lauren; Eccles, Diana; Leach, Martin O; Shanley, Susan; Gilbert, Fiona J; Hanson, Helen; Gallagher, David; Rajashanker, Bala; Whitehouse, Richard W; Koh, Dow-Mu; Sohaib, S Aslam; Evans, D Gareth; Eeles, Rosalind A

2017-07-01

In the United Kingdom, current screening guidelines for TP53 germline mutation carriers solely recommends annual breast MRI, despite the wide spectrum of malignancies typically seen in this group. This study sought to investigate the role of one-off non-contrast whole-body MRI (WB MRI) in the screening of asymptomatic TP53 mutation carriers. 44 TP53 mutation carriers and 44 population controls were recruited. Scans were read by radiologists blinded to participant carrier status. The incidence of malignancies diagnosed in TP53 mutation carriers against general population controls was calculated. The incidences of non-malignant relevant disease and irrelevant disease were measured, as well as the number of investigations required to determine relevance of findings. In TP53 mutation carriers, 6 of 44 (13.6, 95% CI 5.2-27.4%) participants were diagnosed with cancer during the study, all of which would be considered life threatening if untreated. Two were found to have two primary cancers. Two participants with cancer had abnormalities on the MRI which were initially thought to be benign (a pericardial cyst and a uterine fibroid) but transpired to be sarcomas. No controls were diagnosed with cancer. Fifteen carriers (34.1, 95% CI 20.5-49.9%) and seven controls (15.9, 95% CI 6.7-30.1%) underwent further investigations following the WB MRI for abnormalities that transpired to be benign (p = 0.049). The cancer detection rate in this group justifies a minimum baseline non-contrast WB MRI in germline TP53 mutation carriers. This should be adopted into national guidelines for management of adult TP53 mutation carriers in addition to the current practice of contrast enhanced breast MRI imaging.

Spatiotemporal variations of the twentieth century Tibetan Plateau precipitation based on the monthly 2.5° reconstructed data

NASA Astrophysics Data System (ADS)

Shen, Samuel S. P.; Clarke, Gregori; Shen, Bo-Wen; Yao, Tandong

2017-12-01

This paper studies the spatiotemporal variations of precipitation over the Tibetan Plateau (TP) region with latitude and longitude ranges of (25° N, 45° N) and (65° E, 105° E) of the twentieth century from January 1901-December 2000. A long-term (January 1901-December 2009) TP monthly precipitation dataset with 2.5° latitude-longitude resolution is generated in this paper using spectral optimal gridding (SOG) method. The method uses the Global Precipitation Climatology Center (GPCC) ground station data to anchor the basis of empirical orthogonal functions (EOFs) computed from the Global Precipitation Climatology Project (GPCP) data. Our gridding takes teleconnection into account and uses data from stations both within and outside of the TP region. While the annual total precipitation increased at an approximate rate of 2.6 mm per decade in the period of 1971-2000 exists, no significant increase of TP precipitation from 1901 to 2000 was found. Our rate is less than those of previous publications based only on the TP stations because our data consider the entire TP region, including desert and high-altitude areas. An analysis of extremes and spatiotemporal patterns of our data shows that our reconstructed data can properly quantify the reported disasters of flooding and droughts in India, Bangladesh, and China for the following events: flooding in 1988 and 1998 and drought in 1972. Our time-frequency analysis using the empirical mode decomposition method shows that our nonlinear trend agrees well with the linear trend in the period from 1971 to 2000. The spatiotemporal variation characteristics documented in this paper can help understand atmospheric circulations on TP precipitation and validate the TP precipitation in climate models.

Purification and characterization of tenerplasminin-1, a serine peptidase inhibitor with antiplasmin activity from the coral snake (Micrurus tener tener) venom.

PubMed

Vivas, Jeilyn; Ibarra, Carlos; Salazar, Ana M; Neves-Ferreira, Ana G C; Sánchez, Elda E; Perales, Jonás; Rodríguez-Acosta, Alexis; Guerrero, Belsy

2016-01-01

A plasmin inhibitor, named tenerplasminin-1 (TP1), was isolated from Micrurus tener tener (Mtt) venom. It showed a molecular mass of 6542Da, similarly to Kunitz-type serine peptidase inhibitors. The amidolytic activity of plasmin (0.5nM) on synthetic substrate S-2251 was inhibited by 91% following the incubation with TP1 (1nM). Aprotinin (2nM) used as the positive control of inhibition, reduced the plasmin amidolytic activity by 71%. Plasmin fibrinolytic activity (0.05nM) was inhibited by 67% following incubation with TP1 (0.1nM). The degradation of fibrinogen chains induced by plasmin, trypsin or elastase was inhibited by TP1 at a 1:2, 1:4 and 1:20 enzyme:inhibitor ratio, respectively. On the other hand, the proteolytic activity of crude Mtt venom on fibrinogen chains, previously attributed to metallopeptidases, was not abolished by TP1. The tPA-clot lysis assay showed that TP1 (0.2nM) acts like aprotinin (0.4nM) inducing a delay in lysis time and lysis rate which may be associated with the inhibition of plasmin generated from the endogenous plasminogen activation. TP1 is the first serine protease plasmin-like inhibitor isolated from Mtt snake venom which has been characterized in relation to its mechanism of action, formation of a plasmin:TP1 complex and therapeutic potential as anti-fibrinolytic agent, a biological characteristic of great interest in the field of biomedical research. They could be used to regulate the fibrinolytic system in pathologies such as metastatic cancer, parasitic infections, hemophilia and other hemorrhagic syndromes, in which an intense fibrinolytic activity is observed. Copyright © 2015 Elsevier Inc. All rights reserved.

Modulation of Phosphorylation of Tocopherol and Phosphatidylinositol by hTAP1/SEC14L2-Mediated Lipid Exchange

PubMed Central

Zingg, Jean-Marc; Libinaki, Roksan; Meydani, Mohsen; Azzi, Angelo

2014-01-01

The vitamin E derivative, alpha-tocopheryl phosphate (αTP), is detectable in cultured cells, plasma and tissues in small amounts, suggesting the existence of enzyme(s) with α-tocopherol (αT) kinase activity. Here, we characterize the production of αTP from αT and [γ-32P]-ATP in primary human coronary artery smooth muscle cells (HCA-SMC) using separation by thin layer chromatography (TLC) and subsequent analysis by Ultra Performance Liquid Chromatography (UPLC). In addition to αT, although to a lower amount, also γT is phosphorylated. In THP-1 monocytes, γTP inhibits cell proliferation and reduces CD36 scavenger receptor expression more potently than αTP. Both αTP and γTP activate the promoter of the human vascular endothelial growth factor (VEGF) gene with similar potency, whereas αT and γT had no significant effect. The recombinant human tocopherol associated protein 1 (hTAP1, hSEC14L2) binds both αT and αTP and stimulates phosphorylation of αT possibly by facilitating its transport and presentation to a putative αT kinase. Recombinant hTAP1 reduces the in vitro activity of the phosphatidylinositol-3-kinase gamma (PI3Kγ) indicating the formation of a stalled/inactive hTAP1/PI3Kγ heterodimer. The addition of αT, βT, γT, δT or αTP differentially stimulates PI3Kγ, suggesting facilitated egress of sequestered PI from hTAP1 to the enzyme. It is suggested that the continuous competitive exchange of different lipophilic ligands in hTAPs with cell enzymes and membranes may be a way to make these lipophiles more accessible as substrates for enzymes and as components of specific membrane domains. PMID:24983950

Reactivating TP53 signaling by the novel MDM2 inhibitor DS-3032b as a therapeutic option for high-risk neuroblastoma

PubMed Central

Arnhold, Viktor; Schmelz, Karin; Proba, Jutta; Winkler, Annika; Wünschel, Jasmin; Toedling, Joern; Deubzer, Hedwig E.; Künkele, Annette; Eggert, Angelika; Schulte, Johannes H.; Hundsdoerfer, Patrick

2018-01-01

Fewer than 50% of patients with high-risk neuroblastoma survive five years after diagnosis with current treatment protocols. Molecular targeted therapies are expected to improve survival. Although MDM2 has been validated as a promising target in preclinical models, no MDM2 inhibitors have yet entered clinical trials for neuroblastoma patients. Toxic side effects, poor bioavailability and low efficacy of the available MDM2 inhibitors that have entered phase I/II trials drive the development of novel MDM2 inhibitors with an improved risk-benefit profile. We investigated the effect of the novel MDM2 small molecular inhibitor, DS-3032b, on viability, proliferation, senescence, migration, cell cycle arrest and apoptosis in a panel of six neuroblastoma cell lines with different TP53 and MYCN genetic backgrounds, and assessed efficacy in a murine subcutaneous model for high-risk neuroblastoma. Re-analysis of existing expression data from 476 primary neuroblastomas showed that high-level MDM2 expression correlated with poor patient survival. DS-3032b treatment enhanced TP53 target gene expression and induced G1 cell cycle arrest, senescence and apoptosis. CRISPR-mediated MDM2 knockout in neuroblastoma cells mimicked DS-3032b treatment. TP53 signaling was selectively activated by DS-3032b in neuroblastoma cells with wildtype TP53, regardless of the presence of MYCN amplification, but was significantly reduced by TP53 mutations or expression of a dominant-negative TP53 mutant. Oral DS-3032b administration inhibited xenograft tumor growth and prolonged mouse survival. Our in vitro and in vivo data demonstrate that DS-3032b reactivates TP53 signaling even in the presence of MYCN amplification in neuroblastoma cells, to reduce proliferative capacity and cause cytotoxicity. PMID:29416773

Wee-1 Kinase Inhibition Overcomes Cisplatin Resistance Associated with High-Risk TP53 Mutations in Head and Neck Cancer through Mitotic Arrest Followed by Senescence

PubMed Central

Osman, Abdullah A.; Monroe, Marcus M.; Ortega Alves, Marcus V.; Patel, Ameeta A.; Katsonis, Panagiotis; Fitzgerald, Alison L.; Neskey, David M.; Frederick, Mitchell J.; Woo, Sang Hyeok; Caulin, Carlos; Hsu, Teng-Kuei; McDonald, Thomas O.; Kimmel, Marek; Meyn, Raymond E.; Lichtarge, Olivier; Myers, Jeffrey N.

2015-01-01

Although cisplatin has played a role in “standard-of-care” multimodality therapy for patients with advanced squamous cell carcinoma of the head and neck (HNSCC), the rate of treatment failure remains particularly high for patients receiving cisplatin whose tumors have mutations in the TP53 gene. We found that cisplatin treatment of HNSCC cells with mutant TP53 leads to arrest of cells in the G2 phase of the cell cycle, leading us to hypothesize that the wee-1 kinase inhibitor MK-1775 would abrogate the cisplatin-induced G2 block and thereby sensitize isogenic HNSCC cells with mutant TP53 or lacking p53 expression to cisplatin. We tested this hypothesis using clonogenic survival assays, flow cytometry, and in vivo tumor growth delay experiments with an orthotopic nude mouse model of oral tongue cancer. We also used a novel TP53 mutation classification scheme to identify which TP53 mutations are associated with limited tumor responses to cisplatin treatment. Clonogenic survival analyses indicate that nanomolar concentration of MK-1775 sensitizes HNSCC cells with high-risk mutant p53 to cisplatin. Consistent with its ability to chemosensitize, MK-1775 abrogated the cisplatin-induced G2 block in p53-defective cells leading to mitotic arrest associated with a senescence-like phenotype. Furthermore, MK-1775 enhanced the efficacy of cisplatin in vivo in tumors harboring TP53 mutations. These results indicate that HNSCC cells expressing high-risk p53 mutations are significantly sensitized to cisplatin therapy by the selective wee-1 kinase inhibitor, supporting the clinical evaluation of MK-1775 in combination with cisplatin for the treatment of patients with TP53 mutant HNSCC. PMID:25504633

Antioxidants Supplementation in Elderly Cardiovascular Patients

PubMed Central

Vila, Susana; Azzato, F.; Milei, José

2013-01-01

Supplementation with antioxidants and its benefit-risk relationship have been largely discussed in the elderly population. We evaluated whether antioxidants supplementation improved the biochemical profile associated with oxidative metabolism in elderly cardiovascular patients. Patients (n = 112) received daily supplementation with α-TP 400 mg, beta-carotene 40 mg, and vitamin C 1000 mg for 2 months (treatment). Plasma concentrations of alpha-tocopherol (α-TP), β-carotene (βC), ubiquinol-10 (QH-10), glutathione, and thiobarbituric acid reactive substances (TBARS) were determined before and after treatment. Response to treatment was dependent on pretreatment α-TP and βC levels. Increase in α-TP and βC levels was observed only in patients with basal levels <18 μM for α-TP (P < 0.01) and <0.30 μM for βC (P < 0.02). Ubiquinol-10, glutathione, and TBARS were unaffected by treatment: QH-10 (+57%, F 1,110 = 3.611, P < 0.06, and N.S.), glutathione (+21%, F 1,110 = 2.92, P < 0.09, and N.S.), and TBARS (−29%, F 1,110 = 2.26, P < 0.14, and N.S.). Treatment reduced oxidative metabolism: 5.3% versus 14.6% basal value (F 1,110 = 9.21, P < 0.0003). Basal TBARS/α-TP ratio was higher in smokers compared to nonsmokers: 0.11 ± 0.02 versus 0.06 ± 0.01 (F 32,80 = 1.63, P < 0.04). Response to antioxidant supplementation was dependent on basal plasma levels of α-TP and βC. Smoking status was strongly associated with atherosclerotic cardiovascular disease and high TBARS/α-TP ratio (lipid peroxidation). PMID:24489984

Mutations in TP53 are a prognostic factor in colorectal hepatic metastases undergoing surgical resection.

PubMed

Molleví, David G; Serrano, Teresa; Ginestà, Mireia M; Valls, Joan; Torras, Jaume; Navarro, Matilde; Ramos, Emilio; Germà, Josep R; Jaurrieta, Eduardo; Moreno, Víctor; Figueras, Joan; Capellà, Gabriel; Villanueva, Alberto

2007-06-01

The aim of this study was to analyze the prognostic value of TP53 mutations in a consecutive series of patients with hepatic metastases (HMs) from colorectal cancer undergoing surgical resection. Ninety-one patients with liver metastases from colorectal carcinoma were included. Mutational analysis of TP53, exons 4-10, was performed by single-strand conformation polymorphism and sequencing. P53 and P21 protein immunostaining was assessed. Multivariate Cox models were adjusted for gender, number of metastasis, resection margin, presence of TP53 mutations and chemotherapy treatment. Forty-six of 91 (50.05%) metastases showed mutations in TP53, observed mainly in exons 5-8, although 14.3% (n = 13) were located in exons 9 and 10. Forty percent (n = 22) were protein-truncating mutations. TP53 status associated with multiple (> or =3) metastases (65.6%, P = 0.033), advanced primary tumor Dukes' stage (P = 0.011) and younger age (<57 years old, P = 0.03). Presence of mutation associated with poor prognosis in univariate (P = 0.017) and multivariate Cox model [hazard ratio (HR) = 1.80, 95% confidence interval (CI) = 1.07-3.06, P = 0.028]. Prognostic value was maintained in patients undergoing radical resection (R0 series, n = 79, P = 0.014). Mutation associated with a worse outcome in chemotherapy-treated patients (HR = 2.54, 95% CI = 1.12-5.75, P = 0.026). The combination of > or =3 metastases and TP53 mutation identified a subset of patients with very poor prognosis (P = 0.009). P53 and P21 protein immunostaining did not show correlation with survival. TP53 mutational status seems to be an important prognostic factor in patients undergoing surgical resection of colorectal cancer HMs.

Interaction of DNA and mononucleotides with theophylline investigated using electrochemical biosensors and biosensing.

PubMed

Nemčeková, Katarína; Labuda, Ján; Milata, Viktor; Blaškovičová, Jana; Sochr, Jozef

2018-05-03

The understanding of DNA-drug interaction mechanism is among the important aspects of biological studies for drug design, discovery and pharmaceutical development processes. Published rather detailed FTIR and UV-visible spectroscopic studies on the interactions of theophylline, theobromine and caffeine with calf thymus DNA have shown effective binding of these methylxanthine derivatives to DNA and RNA involving H-bonds. However, to our knowledge, there is no such investigation using electrochemical approach. As a novelty of the study, in this paper the bioelectrochemical approach has been chosen for the investigation of an interaction of low molecular salmon sperm dsDNA, ssDNA and mononucleotides with theophylline (TP) in aqueous phosphate buffered medium using DNA-based electrochemical biosensors and biosensing in solution phase. Exploitation of the electrochemical approach via changes in square wave voltammetric responses of deoxyguanosine (dGuo) and deoxyadenosine (dAdo) provided a new indication on preferential association of TP with dGuo in the case of double helical dsDNA structure which was not reported previously. Moreover, an attachment of TP molecules outside DNA was found in the presence of high concentration of 3.3 × 10 -4  M TP in solution which diminishes the electron transfer and leads to the difficulties in quantitative evaluation of the TP and dGuo voltammetric responses. The changes in UV-vis and FTIR spectra obtained in the same medium confirmed the association interaction of TP with both nucleobases. Utilizing the model and the published energies of hydrogen bonding stabilization, the formation of a DNA-TP complex was predicted through the intermolecular H-bonds between TP and the NH-CO moiety of guanine and the N-NH 2 moiety of adenine. Copyright © 2018 Elsevier B.V. All rights reserved.

Clinical performance evaluation of total protein measurement by digital refractometry and characterization of non-protein solute interferences.

PubMed

Hunsaker, Joshua J H; Wyness, Sara P; Snow, Taylor M; Genzen, Jonathan R

2016-12-01

Refractometric methods to measure total protein (TP) in serum and plasma specimens have been replaced by automated biuret methods in virtually all routine clinical testing. A subset of laboratories, however, still report using refractometry to measure TP in conjunction with serum protein electrophoresis. The objective of this study was therefore to conduct a modern performance evaluation of a digital refractometer for TP measurement. Performance evaluation of a MISCO Palm Abbe™ digital refractometer was conducted through device familiarization, carryover, precision, accuracy, linearity, analytical sensitivity, analytical specificity, and reference interval verification. Comparison assays included a manual refractometer and an automated biuret assay. Carryover risk was eliminated using a demineralized distilled water (ddH 2 O) wash step. Precision studies demonstrated overall imprecision of 2.2% CV (low TP pool) and 0.5% CV (high TP pool). Accuracy studies demonstrated correlation to both manual refractometry and the biuret method. An overall positive bias (+5.0%) was observed versus the biuret method. On average, outlier specimens had an increased triglyceride concentration. Linearity was verified using mixed dilutions of: a) low and high concentration patient pools, or b) albumin-spiked ddH 2 O and high concentration patient pool. Decreased recovery was observed using ddH 2 O dilutions at low TP concentrations. Significant interference was detected at high concentrations of glucose (>267 mg/dL) and triglycerides (>580 mg/dL). Current laboratory reference intervals for TP were verified. Performance characteristics of this digital refractometer were validated in a clinical laboratory setting. Biuret method remains the preferred assay for TP measurement in routine clinical analyses.

Enhanced Surface Warming and Accelerated Snow Melt in the Himalayas and Tibetan Plateau Induced by Absorbing Aerosols

NASA Technical Reports Server (NTRS)

Lau, William K.; Kim, Maeng-Ki; Kim, Kyu-Myong; Lee, Woo-Seop

2010-01-01

Numerical experiments with the NASA finite-volume general circulation model show that heating of the atmosphere by dust and black carbon can lead to widespread enhanced warming over the Tibetan Plateau (TP) and accelerated snow melt in the western TP and Himalayas. During the boreal spring, a thick aerosol layer, composed mainly of dust transported from adjacent deserts and black carbon from local emissions, builds up over the Indo-Gangetic Plain, against the foothills of the Himalaya and the TP. The aerosol layer, which extends from the surface to high elevation (approx.5 km), heats the mid-troposphere by absorbing solar radiation. The heating produces an atmospheric dynamical feedback the so-called elevated-heat-pump (EHP) effect, which increases moisture, cloudiness, and deep convection over northern India, as well as enhancing the rate of snow melt in the Himalayas and TP. The accelerated melting of snow is mostly confined to the western TP, first slowly in early April and then rapidly from early to mid-May. The snow cover remains reduced from mid-May through early June. The accelerated snow melt is accompanied by similar phases of enhanced warming of the atmosphere-land system of the TP, with the atmospheric warming leading the surface warming by several days. Surface energy balance analysis shows that the short-wave and long-wave surface radiative fluxes strongly offset each other, and are largely regulated by the changes in cloudiness and moisture over the TP. The slow melting phase in April is initiated by an effective transfer of sensible heat from a warmer atmosphere to land. The rapid melting phase in May is due to an evaporation-snow-land feedback coupled to an increase in atmospheric moisture over the TP induced by the EHP effect.

Identification of Quantitative Trait Loci Controlling Root and Shoot Traits Associated with Drought Tolerance in a Lentil (Lens culinaris Medik.) Recombinant Inbred Line Population

PubMed Central

Idrissi, Omar; Udupa, Sripada M.; De Keyser, Ellen; McGee, Rebecca J.; Coyne, Clarice J.; Saha, Gopesh C.; Muehlbauer, Fred J.; Van Damme, Patrick; De Riek, Jan

2016-01-01

Drought is one of the major abiotic stresses limiting lentil productivity in rainfed production systems. Specific rooting patterns can be associated with drought avoidance mechanisms that can be used in lentil breeding programs. In all, 252 co-dominant and dominant markers were used for Quantitative Trait Loci (QTL) analysis on 132 lentil recombinant inbred lines based on greenhouse experiments for root and shoot traits during two seasons under progressive drought-stressed conditions. Eighteen QTLs controlling a total of 14 root and shoot traits were identified. A QTL-hotspot genomic region related to a number of root and shoot characteristics associated with drought tolerance such as dry root biomass, root surface area, lateral root number, dry shoot biomass and shoot length was identified. Interestingly, a QTL (QRSratioIX-2.30) related to root-shoot ratio, an important trait for drought avoidance, explaining the highest phenotypic variance of 27.6 and 28.9% for the two consecutive seasons, respectively, was detected. This QTL was closed to the co-dominant SNP marker TP6337 and also flanked by the two SNP TP518 and TP1280. An important QTL (QLRNIII-98.64) related to lateral root number was found close to TP3371 and flanked by TP5093 and TP6072 SNP markers. Also, a QTL (QSRLIV-61.63) associated with specific root length was identified close to TP1873 and flanked by F7XEM6b SRAP marker and TP1035 SNP marker. These two QTLs were detected in both seasons. Our results could be used for marker-assisted selection in lentil breeding programs targeting root and shoot characteristics conferring drought avoidance as an efficient alternative to slow and labor-intensive conventional breeding methods. PMID:27602034

Age at cancer onset in germline TP53 mutation carriers: association with polymorphisms in predicted G-quadruplex structures

PubMed Central

Hainaut, Pierre

2014-01-01

Germline TP53 mutations predispose to multiple cancers defining Li-Fraumeni/Li-Fraumeni-like syndrome (LFS/LFL), a disease with large individual disparities in cancer profiles and age of onset. G-quadruplexes (G4s) are secondary structural motifs occurring in guanine tracks, with regulatory effects on DNA and RNA. We analyzed 85 polymorphisms within or near five predicted G4s in TP53 in search of modifiers of penetrance of LFS/LFL in Brazilian cancer families with (n = 35) or without (n = 110) TP53 mutations. Statistical analyses stratified on family structure showed that cancer tended to occur ~15 years later in mutation carriers who also carried the variant alleles of two polymorphisms within predicted G4-forming regions, rs17878362 (TP53 PIN3, 16 bp duplication in intron 3; P = 0.082) and rs17880560 (6 bp duplication in 3′ flanking region; P = 0.067). Haplotype analysis showed that this inverse association was driven by the polymorphic status of the remaining wild-type (WT) haplotype in mutation carriers: in carriers with a WT haplotype containing at least one variant allele of rs17878362 or rs17880560, cancer occurred ~15 years later than in carriers with other WT haplotypes (P = 0.019). No effect on age of cancer onset was observed in subjects without a TP53 mutation. The G4 in intron 3 has been shown to regulate alternative p53 messenger RNA splicing, whereas the biological roles of predicted G4s in the 3′ flanking region remain to be elucidated. In conclusion, this study demonstrates that G4 polymorphisms in haplotypes of the WT TP53 allele have an impact on LFS/LFL penetrance in germline TP53 mutation carriers. PMID:24336192

Molecular docking, molecular modeling, and molecular dynamics studies of azaisoflavone as dual COX-2 inhibitors and TP receptor antagonists.

PubMed

Hadianawala, Murtuza; Mahapatra, Amarjyoti Das; Yadav, Jitender K; Datta, Bhaskar

2018-02-26

Designed multi-target ligand (DML) is an emerging strategy for the development of new drugs and involves the engagement of multiple targets with the same moiety. In the context of NSAIDs it has been suggested that targeting the thromboxane prostanoid (TP) receptor along with cyclooxygenase-2 (COX-2) may help to overcome cardiovascular (CVS) complications associated with COXIBs. In the present work, azaisoflavones were studied for their COX-2 and TP receptor binding activities using structure based drug design (SBDD) techniques. Flavonoids were selected as a starting point based on their known COX-2 inhibitory and TP receptor antagonist activity. Iterative design and docking studies resulted in the evolution of a new class scaffold replacing the benzopyran-4-one ring of flavonoids with quinolin-4-one. The docking and binding parameters of these new compounds are found to be promising in comparison to those of selective COX-2 inhibitors, such as SC-558 and celecoxib. Owing to the lack of structural information, a model for the TP receptor was generated using a threading base alignment method with loop optimization performed using an ab initio method. The model generated was validated against known antagonists for TP receptor using docking/MMGBSA. Finally, the molecules that were designed for selective COX-2 inhibition were docked into the active site of the TP receptor. Iterative structural modifications and docking on these molecules generated a series which displays optimum docking scores and binding interaction for both targets. Molecular dynamics studies on a known TP receptor antagonist and a designed molecule show that both molecules remain in contact with protein throughout the simulation and interact in similar binding modes. Graphical abstract ᅟ.

Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary.

PubMed

Ahmed, Ahmed Ashour; Etemadmoghadam, Dariush; Temple, Jillian; Lynch, Andy G; Riad, Mohamed; Sharma, Raghwa; Stewart, Colin; Fereday, Sian; Caldas, Carlos; Defazio, Anna; Bowtell, David; Brenton, James D

2010-05-01

Numerous studies have tested the association between TP53 mutations in ovarian cancer and prognosis but these have been consistently confounded by limitations in study design, methodology, and/or heterogeneity in the sample cohort. High-grade serous (HGS) carcinoma is the most clinically important histological subtype of ovarian cancer. As these tumours may arise from the ovary, Fallopian tube or peritoneum, they are collectively referred to as high-grade pelvic serous carcinoma (HGPSC). To identify the true prevalence of TP53 mutations in HGPSC, we sequenced exons 2-11 and intron-exon boundaries in tumour DNA from 145 patients. HGPSC cases were defined as having histological grade 2 or 3 and FIGO stage III or IV. Surprisingly, pathogenic TP53 mutations were identified in 96.7% (n = 119/123) of HGPSC cases. Molecular and pathological review of mutation-negative cases showed evidence of p53 dysfunction associated with copy number gain of MDM2 or MDM4, or indicated the exclusion of samples as being low-grade serous tumours or carcinoma of uncertain primary site. Overall, p53 dysfunction rate approached 100% of confirmed HGPSCs. No association between TP53 mutation and progression-free or overall survival was found. From this first comprehensive mapping of TP53 mutation rate in a homogeneous group of HGPSC patients, we conclude that mutant TP53 is a driver mutation in the pathogenesis of HGPSC cancers. Because TP53 mutation is almost invariably present in HGPSC, it is not of substantial prognostic or predictive significance. Copyright (c) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Reversion of apoptotic resistance of TP53-mutated Burkitt lymphoma B-cells to spindle poisons by exogenous activation of JNK and p38 MAP kinases.

PubMed

Farhat, M; Poissonnier, A; Hamze, A; Ouk-Martin, C; Brion, J-D; Alami, M; Feuillard, J; Jayat-Vignoles, C

2014-05-01

Defects in apoptosis are frequently the cause of cancer emergence, as well as cellular resistance to chemotherapy. These phenotypes may be due to mutations of the tumor suppressor TP53 gene. In this study, we examined the effect of various mitotic spindle poisons, including the new isocombretastatin derivative isoNH2CA-4 (a tubulin-destabilizing molecule, considered to bind to the colchicine site by analogy with combretastatin A-4), on BL (Burkitt lymphoma) cells. We found that resistance to spindle poison-induced apoptosis could be reverted in tumor protein p53 (TP53)-mutated cells by EBV (Epstein Barr virus) infection. This reversion was due to restoration of the intrinsic apoptotic pathway, as assessed by relocation of the pro-apoptotic molecule Bax to mitochondria, loss of mitochondrial integrity and activation of the caspase cascade with PARP (poly ADP ribose polymerase) cleavage. EBV sensitized TP53-mutated BL cells to all spindle poisons tested, including vincristine and taxol, an effect that was systematically downmodulated by pretreatment of cells with inhibitors of p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinases. Exogenous activation of p38 and JNK pathways by dihydrosphingosine reverted resistance of TP53-mutated BL cells to spindle poisons. Dihydrosphingosine treatment of TP53-deficient Jurkat and K562 cell lines was also able to induce cell death. We conclude that activation of p38 and JNK pathways may revert resistance of TP53-mutated cells to spindle poisons. This opens new perspectives for developing alternative therapeutic strategies when the TP53 gene is inactivated.

Vanillic acid attenuates testosterone-induced benign prostatic hyperplasia in rats and inhibits proliferation of prostatic epithelial cells

PubMed Central

Kim, Hye-Lin; Youn, Dong-Hyun; Kang, JongWook; Lim, Seona; Jeong, Mi-Young; Sethi, Gautam; Park, Sung-Joo; Ahn, Kwang Seok; Um, Jae-Young

2017-01-01

Benign prostatic hyperplasia (BPH) is a common disease in the male population, especially in elderly men. Vanillic acid (VA), a dihydroxybenzoic derivative used as a flavoring agent, is reported to have an anti-inflammatory effect. However, there are no reports of its effects on BPH to date. BPH was induced with a pre-4-week treatment of daily subcutaneous injections of testosterone propionate (TP), and the normal control group received injections of ethanol with corn oil instead. Six weeks of further injections were done with (a) ethanol with corn oil, (b) TP only, (c) TP + finasteride, and (d) TP + VA. Finasteride was used as a positive control group. VA had protective effects on the TP-induced BPH. In the VA treatment group, the prostate weight was reduced, and the histological changes including the epithelial thickness and lumen area were restored like in the normal control group. Furthermore, in the VA treatment group, two proliferation related factors, high molecular weight cytokeratin 34βE12 and α smooth muscle actin, were significantly down-regulated compared to the TP-induced BPH group. The expressions of dihydrotestosterone and 5α-reductase, the most crucial factors in BPH development, were suppressed by VA treatment. Expressions of the androgen receptor, estrogen receptor α and steroid receptor coactivator 1 were also significantly inhibited by VA compared to the TP-induced BPH group. In addition, we established an in vitro model for BPH by treating a normal human prostatic epithelial cell line RWPE-1 with TP. VA successfully inhibited proliferation and BPH-related factors in a concentration-dependent manner in this newly established model. These results suggest a new and potential pharmaceutical therapy of VA in the treatment of BPH. PMID:29152074

Modeling the Etiology of p53-mutated Cancer Cells*

PubMed Central

Perez, Ricardo E.; Shen, Hong; Duan, Lei; Kim, Reuben H.; Kim, Terresa; Park, No-Hee; Maki, Carl G.

2016-01-01

p53 gene mutations are among the most common alterations in cancer. In most cases, missense mutations in one TP53 allele are followed by loss-of-heterozygosity (LOH), so tumors express only mutant p53. TP53 mutations and LOH have been linked, in many cases, with poor therapy response and worse outcome. Despite this, remarkably little is known about how TP53 point mutations are acquired, how LOH occurs, or the cells involved. Nutlin-3a occupies the p53-binding site in MDM2 and blocks p53-MDM2 interaction, resulting in the stabilization and activation of p53 and subsequent growth arrest or apoptosis. We leveraged the powerful growth inhibitory activity of Nutlin-3a to select p53-mutated cells and examined how TP53 mutations arise and how the remaining wild-type allele is lost or inactivated. Mismatch repair (MMR)-deficient colorectal cancer cells formed heterozygote (p53 wild-type/mutant) colonies when cultured in low doses of Nutlin-3a, whereas MMR-corrected counterparts did not. Placing these heterozygotes in higher Nutlin-3a doses selected clones in which the remaining wild-type TP53 was silenced. Our data suggest silencing occurred through a novel mechanism that does not involve DNA methylation, histone methylation, or histone deacetylation. These data indicate MMR deficiency in colorectal cancer can give rise to initiating TP53 mutations and that TP53 silencing occurs via a copy-neutral mechanism. Moreover, the data highlight the use of MDM2 antagonists as tools to study mechanisms of TP53 mutation acquisition and wild-type allele loss or silencing in cells with defined genetic backgrounds. PMID:27022024

Development and validation of a competitive enzyme-linked immunosorbent assay for the measurement of total plasma immunoglobulins in healthy loggerhead sea (Caretta caretta) and green turtles (Chelonia mydas).

PubMed

Kaplan, Amy J; Stacy, Nicole I; Jacobson, Elliott; Le-Bert, Carolina R; Nollens, Hendrik H; Origgi, Francesco C; Green, Linda G; Bootorabi, Shadi; Bolten, Alan; Hernandez, Jorge A

2016-01-01

The quantification of circulating plasma immunoglobulins represents a valuable diagnostic tool in human and veterinary immunology, although its application is very limited in reptile medicine to date. The objectives of our study were the development and standardization of a competitive enzyme-linked immunosorbent assay (cELISA) for the measurement of total plasma immunoglobulins (Igs; both IgM and IgY) in loggerhead sea turtles (LST; Caretta caretta; n = 254) and green turtles (GT; Chelonia mydas; n = 111), the establishment of reference intervals for Ig for both species, and the examination of associations between Ig and total protein (TP), condition index, and water temperature. The cELISA for Ig was successfully developed and optimized. Reference intervals for Ig were 0.38-0.94 g/dL in LST (median: 0.59 g/dL; range: 0.16-2.15 g/dL) and 0.40-0.85 g/dL in GT (median: 0.58 g/dL; range: 0.18-1.80 g/dL). In LST, there were positive linear relationships of Ig with TP, and TP with Ig and condition index, and a negative relationship of Ig with condition index. The positive linear relationships of Ig with TP, and TP with Ig were also identified in GT. These positive associations of Ig and TP were expected, as Ig represents fractions of TP, and TP reportedly increases with straight carapace length and weight. The negative association of Ig with condition index may indicate potential biological variations. The cELISA and reference intervals for total Ig of LST and GT presented herein have the potential to be useful as a diagnostic and research tool for sea turtle immunology. © 2015 The Author(s).

Quantum secret information equal exchange protocol based on dense coding

NASA Astrophysics Data System (ADS)

Jiang, Ying-Hua; Zhang, Shi-Bin; Dai, Jin-Qiao; Shi, Zhi-Ping

2018-04-01

In this paper, we design a novel quantum secret information equal exchange protocol, which implements the equal exchange of secret information between the two parties with the help of semi-trusted third party (TP). In the protocol, EPR pairs prepared by the TP are, respectively, distributed to both the communication parties. Then, the two parties perform Pauli operation on each particle and return the new particles to TP, respectively. TP measures each new pair with Bell basis and announces the measurement results. Both parties deduce the secret information of each other according to the result of announcement by TP. Finally, the security analysis shows that this protocol solves the problem about equal exchange of secret information between two parties and verifies the security of semi-trusted TPs. It proves that the protocol can effectively resist glitch attacks, intercept retransmission attacks and entanglement attack.

Analysis of TP53 gene expression and p53 level of human hypopharyngeal FaDu (HTB-43) head and neck cancer cell line after microRNA-181a inhibition.

PubMed

Cheah, Y K; Cheng, R W; Yeap, S K; Khoo, C H; See, H S

2014-03-17

The identification of new biomarkers for early detection of highly recurrent head and neck cancer is urgently needed. MicroRNAs (miRNAs) are small and non-coding RNAs that regulate cancer-related gene expression, such as tumor protein 53 (TP53) gene expression. This study was carried out to analyze TP53 gene expression using real-time PCR and to determine changes in intracellular p53 level by flow cytometry after downregulation of miRNA-181a miRNA inhibitor in the FaDu cell line. TP53 gene expression showed a 3-fold increment and the p53 protein level was also increased in the miRNA-181a-treated cells. In conclusion, miRNA-181a binds to the TP53 gene and inhibits its expression, decreasing the synthesis of p53.

The effect of redox-active cyanomanganese(I) ligands on intramolecular electron transfer to, and alkyne alignment in, M(CO)(RC[triple bond, length as m-dash]CR)Tp' (M = Mo or W) units.

PubMed

Adams, Christopher J; Connelly, Neil G; Onganusorn, Sriwipha

2009-04-28

The complexes [(eta-C(5)Me(5))(ON)LMn(micro-CN)M(CO)(RC[triple bond, length as m-dash]CR)Tp'](+) (L = CNXyl, M = Mo; L = CNBu(t), M = Mo or W, R = Ph or Me) and trans- or cis-[(dppm){(EtO)(3)P}(OC)(2)Mn(micro-CN)M(CO)(PhC[triple bond, length as m-dash]CPh)Tp'](+), and their linkage isomers [(eta-C(5)Me(5))(ON)LMn(micro-NC)M(CO)(PhC[triple bond, length as m-dash]CPh)Tp'](+) and trans- or cis-[(dppm){(EtO)(3)P}(OC)(2)Mn(micro-NC)M(CO)(PhC[triple bond, length as m-dash]CPh)Tp'](+), undergo two one-electron oxidations. The complexes [(eta-C(5)Me(5))(ON)LMn(micro-XY)M(CO)(RC[triple bond, length as m-dash]CR)Tp'](+) (XY = CN or NC) are oxidised first at the N-bound metal centre and then at the C-bound centre. For [(dppm){(EtO)(3)P}(OC)(2)Mn(micro-XY)M(CO)(PhC[triple bond, length as m-dash]CPh)Tp'](+), the trans isomers are first oxidised at manganese whereas the cis isomers are first oxidised at M. Thus, the order of one-electron oxidation of the two series of binuclear monocations is influenced by linkage isomerisation of the cyanide bridge and cis-trans isomerisation of the Mn(CO)(2) group. IR spectroscopic changes on reaction of Ag(+) with [(eta-C(5)Me(5))(ON)(Bu(t)NC)Mn(micro-CN)W(CO)(MeC[triple bond, length as m-dash]CMe)Tp'](+) are consistent with one-electron at the N-bound tungsten centre. Likewise, trans-[(dppm){(EtO)(3)P}(OC)(2)Mn(micro-NC)M(CO)(PhC[triple bond, length as m-dash]CPh)Tp'](+) (M = Mo or W) give the stable dications [(dppm){(EtO)(3)P}(OC)(2)Mn(micro-NC)M(CO)(PhC[triple bond, length as m-dash]CPh)Tp'](2+). Significantly longer Mn-P bond distances in trans-[(dppm){(EtO)(3)P}(OC)(2)Mn(micro-NC)Mo(CO)(PhC[triple bond, length as m-dash]CPh)Tp'](2+) than in trans-[(dppm){(EtO)(3)P}(OC)(2)Mn(micro-NC)Mo(CO)(PhC[triple bond, length as m-dash]CPh)Tp'](+) are consistent with one-electron oxidation first at Mn(I); the alignment of the (CN)Mn(CO)(2){P(OEt)(3)}(dppm) fragment relative to the alkyne in trans-[(dppm){(EtO)(3)P}(OC)(2)Mn(micro-NC)Mo(CO)(PhC[triple bond, length as m-dash]CPh)Tp'](+) suggests it acts as a pi-acceptor, in contrast to related species such as trans-(NC)Mn(CO)(2){P(OEt)(3)}(dppm) and (NC)Mn(NO){P(OPh)(3)}(pi-C(5)H(4)Me) which behave as simple N-donors.

Jenny Heeter | NREL

Science.gov Websites

Energy Laboratory. NREL/TP-6A20-63052. Heeter, J., G. Barbose, L. Bird, S. Weaver, F. Flores-Espino, K Energy Laboratory. NREL/TP-6A20-54991. Cochran, J., L. Bird, J. Heeter, and D.J. Arent. 2012. Integrating , CO: National Renewable Energy Laboratory. NREL/TP-6A20-53732. Holt, E., J. Sumner, and L. Bird. 2011

A Computer Model Predicting the Thermal Response to Microwave Radiation

DTIC Science & Technology

1982-12-01

While each of these represents the result of a triple integration, the total running time is still only between 3 and 4 main on an IBM 360 for K...T/Tp]Tp + (i-1)T p (3.4.9) M(TN) min(([T-[T/Tp] iTp )/T ],Np) (3.4.10) t(TNTT)= MTN) +rTT 1T (3.4.11) t(,ppPT, ’(,p )T L"’PJ-’P x =x(NJ~1~T~ = 0 if...TRM - SRM1)/TRM 101 .: S . .-. . . . . . . . .. . . . . 4.6. Program Size and Running Time The program requires 252K on the ’GO’ step for an IBM 360

The unusual ISM in Blue and Dusty Gas Rich Galaxies (BADGRS).

NASA Astrophysics Data System (ADS)

Dunne, L.; Zhang, Z.; De Vis, P.; Clark, C. J. R.; Oteo, I.; Maddox, S. J.; Cigan, P.; de Zotti, G.; Gomez, H. L.; Ivison, R. J.; Rowlands, K.; Smith, M. W. L.; van der Werf, P.; Vlahakis, C.; Millard, J. S.

2018-06-01

The Herschel-ATLAS unbiased survey of cold dust in the local Universe is dominated by a surprising population of very blue (FUV - K < 3.5), dust-rich galaxies with high gas fractions ({f_{HI}=M_{HI}/({ M_{\\ast }}+M_{HI})}>0.5). Dubbed `Blue and Dusty Gas Rich Sources' (BADGRS) they have cold diffuse dust temperatures, and the highest dust-to-stellar mass ratios of any galaxies in the local Universe. Here, we explore the molecular ISM in a representative sample of BADGRS, using very deep {CO(J_{up}=1,2,3)} observations across the central and outer disk regions. We find very low CO brightnesses (Tp = 5 - 30 mK), despite the bright far-infrared emission and metallicities in the range 0.5 < Z/Z⊙ < 1.0. The CO line ratios indicate a range of conditions with R_{21}={T_b^{21}/T_b^{10}=0.6-2.1} and R_{31}={T_b^{32}/T_b^{10}=0.2-1.2}. Using a metallicity dependent conversion from CO luminosity to molecular gas mass we find M_{H2}/{M_d}˜ 7-27 and Σ _{H2} = 0.5-6 M_{⊙} {pc^{-2}}, around an order of magnitude lower than expected. The BADGRS have lower molecular gas depletion timescales (τd ˜ 0.5 Gyr) than other local spirals, lying offset from the Kennicutt-Schmidt relation by a similar factor to Blue Compact Dwarf galaxies. The cold diffuse dust temperature in BADGRS (13-16 K) requires an interstellar radiation field 10-20 times lower than that inferred from their observed surface brightness. We speculate that the dust in these sources has either a very clumpy geometry or a very different opacity in order to explain the cold temperatures and lack of CO emission. BADGRS also have low UV attenuation for their UV colour suggestive of an SMC-type dust attenuation curve, different star formation histories or different dust/star geometry. They lie in a similar part of the IRX-β space as z ˜ 5 galaxies and may be useful as local analogues for high gas fraction galaxies in the early Universe.

R2TP/Prefoldin-like component RUVBL1/RUVBL2 directly interacts with ZNHIT2 to regulate assembly of U5 small nuclear ribonucleoprotein

PubMed Central

Cloutier, Philippe; Poitras, Christian; Durand, Mathieu; Hekmat, Omid; Fiola-Masson, Émilie; Bouchard, Annie; Faubert, Denis; Chabot, Benoit; Coulombe, Benoit

2017-01-01

The R2TP/Prefoldin-like (R2TP/PFDL) complex has emerged as a cochaperone complex involved in the assembly of a number of critical protein complexes including snoRNPs, nuclear RNA polymerases and PIKK-containing complexes. Here we report on the use of multiple target affinity purification coupled to mass spectrometry to identify two additional complexes that interact with R2TP/PFDL: the TSC1–TSC2 complex and the U5 small nuclear ribonucleoprotein (snRNP). The interaction between R2TP/PFDL and the U5 snRNP is mostly mediated by the previously uncharacterized factor ZNHIT2. A more general function for the zinc-finger HIT domain in binding RUVBL2 is exposed. Disruption of ZNHIT2 and RUVBL2 expression impacts the protein composition of the U5 snRNP suggesting a function for these proteins in promoting the assembly of the ribonucleoprotein. A possible implication of R2TP/PFDL as a major effector of stress-, energy- and nutrient-sensing pathways that regulate anabolic processes through the regulation of its chaperoning activity is discussed. PMID:28561026

Two-Photon Absorption Based Nanoscopic Velocimeter

NASA Astrophysics Data System (ADS)

Wang, Audrey; Abdalrahman, Akrm; Deng, Jianyu; Wang, Guiren

2017-11-01

Most velocimeters in micro/nanofluidics rely on particles as flow tracers, such as micro Particle Image Velocimetry (μPIV). However, for many microflows, such as electrokinetic and near wall flow, magnetophoresis, acoustophoresis, photophoresis and thermophoresis, particles have different velocity from their surrounding fluids. Although most molecular tracer based velocimeters can use neutral dye to measure average velocity, their temporal and spatial resolution are limited. Stimulated emission depletion (STED) based laser-induced fluorescence photobleaching anemometer (LIFPA), i.e. STED-LIFPA has achieved 70 nm spatial resolution. However, STED nanoscopy is very complicated for most users. Here we developed a two-photon absorption LIFPA (TP-LIFPA), which is relatively easier to operate. TP-LIFPA can take advantage of the two-photon microscopy to increase spatial resolution. We use a femtolaser to excite a dye. A microcapillary tube is used to test the feasibility of TP-LIFPA. TP-LIFPA can successfully measure the velocity profile in the capillary. The resolution of TP-LIFPA is estimated to be about 90 nm. The work indicates TP-LIFPA is a new promising nanoscopic velocimeter for interfacial flows, especially within 100 nm at the interfacial area between two phases in the future. The work was supported by NSF under Grant No. MRI CBET-1040227.

Seasonal variation and source analysis of persistent organic pollutants in the atmosphere over the western Tibetan Plateau.

PubMed

Zhang, Jingyi; Wang, Xiaoping; Gong, Ping; Wang, Chuanfei; Sun, Dianchao

2018-06-08

Over the past few decades, the Tibetan Plateau (TP) region has become gradually contaminated by persistent organic pollutants (POPs). The picture regarding POPs is clear in the central and southern parts of the TP; however, few observational campaigns have focused on the western TP. To clarify the concentrations, seasonal trends and source regions of POPs in the western TP, a first study of POPs in Muztagh Ata (westerly region) and a long-term (5 years) monitoring program in Ngari (transect region influenced by both the Indian monsoon and westerly climate) were conducted. Except for hexachlorobenzene (HCB) and polychlorinated biphenyls (PCBs), relatively low POP levels were observed in the western TP. In Muztagh Ata, dichlorodiphenyltrichloroethanes (DDTs) showed higher concentrations in winter and lower ones in summer, whereas at Ngari, higher DDTs and hexachlorocyclohexanes (HCHs) concentrations were observed in summer as compared with winter. Source diagnosis indicated that Xinjiang and central Asia were the main source regions for POPs in Muztagh Ata and that westerly winds play a key role in transporting POPs from central Asia. No correlation was found between the height of the atmospheric boundary layer and the concentrations of POPs over the TP.

Climate variability rather than overstocking causes recent large scale cover changes of Tibetan pastures.

PubMed

Lehnert, L W; Wesche, K; Trachte, K; Reudenbach, C; Bendix, J

2016-04-13

The Tibetan Plateau (TP) is a globally important "water tower" that provides water for nearly 40% of the world's population. This supply function is claimed to be threatened by pasture degradation on the TP and the associated loss of water regulation functions. However, neither potential large scale degradation changes nor their drivers are known. Here, we analyse trends in a high-resolution dataset of grassland cover to determine the interactions among vegetation dynamics, climate change and human impacts on the TP. The results reveal that vegetation changes have regionally different triggers: While the vegetation cover has increased since the year 2000 in the north-eastern part of the TP due to an increase in precipitation, it has declined in the central and western parts of the TP due to rising air temperature and declining precipitation. Increasing livestock numbers as a result of land use changes exacerbated the negative trends but were not their exclusive driver. Thus, we conclude that climate variability instead of overgrazing has been the primary cause for large scale vegetation cover changes on the TP since the new millennium. Since areas of positive and negative changes are almost equal in extent, pasture degradation is not generally proceeding.

Time perspective, socioeconomic status, and psychological distress in chronic pain patients.

PubMed

Dany, Lionel; Roussel, Philippe; Laguette, Vanessa; Lagouanelle-Simeoni, Marie-Claude; Apostolidis, Themis

2016-01-01

Time perspective (TP) is a fundamental dimension of the psychological construction of time. It refers to a subjective experience and can be defined as the relationship that individuals and groups have with the present, past, and future. Studies have shown that it is interesting to take into account TP in the field of health, especially for the study of the psychological distress (PD) of individuals faced with aversive situations. We conducted a research, which aimed to explore the relationship between TP and PD in patients with chronic pain. A total of 264 first-time patients (72.3% women; mean age = 49 years) at CHU Timone (Marseille) pain center answered a questionnaire included TP, socioeconomic status, pain beliefs (PB), pain characteristics, and sociodemographic characteristics. Using hierarchical regression analyses adjusted to the characteristics of pain, sociodemographic characteristics, and PB, we can observe significant relationships between different components of TP, socioeconomic status, and PD. These results emphasize the importance of TP as psychosocial variable in the analysis of PD in patients with chronic pain. These results also lead us to point out the role of the socioeconomic status that predicts levels of PD.

Characterization of a Thermophilic Bacteriophage for Bacillus stearothermophilus1

PubMed Central

Saunders, Grady F.; Campbell, L. Leon

1966-01-01

Saunders, Grady F. (University of Illinois, Urbana), and L. Leon Campbell. Characterization of a thermophilic bacteriophage for Bacillus stearothermophilus. J. Bacteriol. 91:340–348. 1965.—The biological and physical-chemical properties of the thermophilic bacteriophage TP-84 were investigated. TP-84 was shown to be lytic for 3 of 24 strains of Bacillus stearothermophilus tested over the temperature range of 43 to 76 C. The latent period of TP-84 on B. stearothermophilus strain 10 was 22 to 24 min. TP-84 has a hexagonal head, 53 mμ in diameter and 30 mμ on a side; its tail is 130 mμ long and 3 to 5 mμ wide. The phage has an S5020,w of 436, and bands at a density of 1.508 g/cc in CsCl (pH 8.5). The diffusion coefficient of TP-84 was calculated to be 6.19 × 10−8 cm2/sec. From the sedimentation and diffusion data, a particle molecular weight of 50 million daltons was calculated for TP-84. The phage DNA has a base composition of 42% guanine + cytosine, deduced from buoyant density and melting temperature measurements. Images PMID:5903101

Evolutionary Action Score of TP53 Identifies High-Risk Mutations Associated with Decreased Survival and Increased Distant Metastases in Head and Neck Cancer.

PubMed

Neskey, David M; Osman, Abdullah A; Ow, Thomas J; Katsonis, Panagiotis; McDonald, Thomas; Hicks, Stephanie C; Hsu, Teng-Kuei; Pickering, Curtis R; Ward, Alexandra; Patel, Ameeta; Yordy, John S; Skinner, Heath D; Giri, Uma; Sano, Daisuke; Story, Michael D; Beadle, Beth M; El-Naggar, Adel K; Kies, Merrill S; William, William N; Caulin, Carlos; Frederick, Mitchell; Kimmel, Marek; Myers, Jeffrey N; Lichtarge, Olivier

2015-04-01

TP53 is the most frequently altered gene in head and neck squamous cell carcinoma, with mutations occurring in over two-thirds of cases, but the prognostic significance of these mutations remains elusive. In the current study, we evaluated a novel computational approach termed evolutionary action (EAp53) to stratify patients with tumors harboring TP53 mutations as high or low risk, and validated this system in both in vivo and in vitro models. Patients with high-risk TP53 mutations had the poorest survival outcomes and the shortest time to the development of distant metastases. Tumor cells expressing high-risk TP53 mutations were more invasive and tumorigenic and they exhibited a higher incidence of lung metastases. We also documented an association between the presence of high-risk mutations and decreased expression of TP53 target genes, highlighting key cellular pathways that are likely to be dysregulated by this subset of p53 mutations that confer particularly aggressive tumor behavior. Overall, our work validated EAp53 as a novel computational tool that may be useful in clinical prognosis of tumors harboring p53 mutations. ©2015 American Association for Cancer Research.

Evolutionary Action score of TP53 (EAp53) identifies high risk mutations associated with decreased survival and increased distant metastases in head and neck cancer

PubMed Central

Neskey, David M.; Osman, Abdullah A.; Ow, Thomas J.; Katsonis, Panagiotis; McDonald, Thomas; Hicks, Stephanie C.; Hsu, Teng-Kuei; Pickering, Curtis R.; Ward, Alexandra; Patel, Ameeta; Yordy, John S.; Skinner, Heath D.; Giri, Uma; Sano, Daisuke; Story, Michael D.; Beadle, Beth M.; El-Naggar, Adel K.; Kies, Merrill S.; William, William N.; Caulin, Carlos; Frederick, Mitchell; Kimmel, Marek; Myers, Jeffrey N.; Lichtarge, Olivier

2015-01-01

TP53 is the most frequently altered gene in head and neck squamous cell carcinoma (HNSCC) with mutations occurring in over two third of cases, but the prognostic significance of these mutations remains elusive. In the current study, we evaluated a novel computational approach termed Evolutionary Action (EAp53) to stratify patients with tumors harboring TP53 mutations as high or low risk, and validated this system in both in vivo and in vitro models. Patients with high risk TP53 mutations had the poorest survival outcomes and the shortest time to the development of distant metastases. Tumor cells expressing high risk TP53 mutations were more invasive and tumorigenic and they exhibited a higher incidence of lung metastases. We also documented an association between the presence of high risk mutations and decreased expression of TP53 target genes, highlighting key cellular pathways that are likely to be dysregulated by this subset of p53 mutations which confer particularly aggressive tumor behavior. Overall, our work validated EAp53 as a novel computational tool that may be useful in clinical prognosis of tumors harboring p53 mutations. PMID:25634208

Hydrologic Linkages Between Floodplain Wetlands and Adjacent Agricultural Lands

NASA Astrophysics Data System (ADS)

Matteson, C.; Jackson, C. R.; Wilde, S. B.; Batzer, D.; Shelton, J.; Jeffers, J. B.

2017-12-01

Depending on wetland position relative to dominant flow pathways, wetlands can provide biogeochemical processing and water quality improvement in agricultural settings, particularly with respect to nutrients. Here we evaluate field-to-stream water quality gradients across a forested alluvial swamp and through a ditched wetland swale on the same site. During 2016 and 2017, water samples collected on a farm from shallow piezometers and surface water were analyzed for total oxidized nitrogen (TOxN), total phosphorus (TP), and microbial abundance. A 54-acre alluvial swamp borders the northern side of the study farm. Toeslope nutrient concentrations in shallow groundwater and surfacewater are elevated relative to background levels, with median values of 13.25 mg/l/TOxN and 47.60 µg/l/TP. Shallow groundwater and surfacewater concentrations are substantially lower only a few meters into the floodplain wetland and lower still (0.13 mg/l/TOxN and 29.67 µg/l/TP) at discharge points to an adjacent creek. Across the farm, an 18-acre wetland swale has been ditched, drained, and cropped. TOxN levels entering and exiting the ditched swale do not mitigate as efficiently, median values of 3.91 mg/l/TOxN reduce to 1.45 mg/l/TOxN, while TP input and reduction exceed the alluvial swamp by starting at 141.67 µg/l/TP at the inflow and discharging into a large river at 57.40 µg/l/TP. Microbial communities in seeps and surfacewater also vary systematically with geographic position. Higher proportions of Cyanobacteria, Turbidity indicators, and Diatom communities are observed in the ditched swale, and input areas of the alluvial swamp. ANOVA tests of TOxN (P<0.001) and TP (P=0.9) change across the alluvial swamp suggest effective processing of TOxN. While P values for TOxN and TP in the ditched swale, yield P=0.9 for TOxN and P=1.0 for TP indicating reduced efficiency of mitigation. Though values of both TOxN and TP do decrease before discharge into the river, they are not statistically significant and still greater values than the alluvial swamp. Dissipation of microbial indicators shows pollution mitigation further into the alluvial swamp. Though pollutant additions have been similar into both wetland types, water quality improvements are distinct in the alluvial swamp.

ACUTE CHANGES IN PASSIVE GLENOHUMERAL ROTATION FOLLOWING TENNIS PLAY EXPOSURE IN ELITE FEMALE PLAYERS

PubMed Central

Kibler, W. Ben; Myers, Natalie L.; Smith, Belinda J.

2016-01-01

Background Alterations in glenohumeral (GH) rotation especially internal rotation and total range of motion have been associated with altered GH kinematics and susceptibility to injury. Researchers have evaluated long-term change in baseball and tennis players, and short-term changes in baseball players. However, acute (short-term) changes in GH rotation have not been evaluated in tennis players. Hypotheses/Purpose The purpose of this study was to quantify short-term glenohumeral rotational changes within a group of professional women's tennis players following competitive play. It was hypothesized that there would be acute alterations in passive glenohumeral internal rotation and total range of motion following episodes of tennis play. Study Design Cohort Study Methods Passive glenohumeral external rotation (GER), glenohumeral internal rotation (GIR), and total range of motion (TROM) were evaluated in a cohort of 79 professional adult female tennis players. Measurements were taken at three different time points (TP): baseline before match play (TP1), immediately after match play (TP2), and 24-hours after baseline (TP3). Results There was a statistically significant decrease in the mean GIR from TP1 (43 ± 11 °) to TP2 (39 ± 9 °) (p=0.002) and from TP1 to TP3 (38 ± 10 °) (p=0.001). All measures were at the level of minimal detectable change (MDC) (4 °) indicating clinical significance. There was a decrease in mean TROM from TP1 (146 ± 11 °) to TP2 (142 ± 12 °) (p=0.04), which was not above MDC (7 °). Subgroup analysis showed that 47% of the players demonstrated a decrease in GIR beyond MDC, and 37% demonstrated a decrease in TROM beyond MDC. GER remained unchanged across all time points (p>0.05). Conclusion Both GIR and TROM were reduced after acute exposure to tennis play. In a large subgroup of the cohort, the changes were clinically significant and approached values previously demonstrated to be associated with increased injury risk. Given the changes in glenohumeral motion following acute exposure to tennis, evaluation of players for significant motion alterations following overhead activity and intervention strategies to minimize such alterations in these players are recommended for high level tennis players. Level of evidence Level 3 PMID:27104056

Family leadership styles and adolescent dietary and physical activity behaviors: a cross-sectional study

PubMed Central

2012-01-01

Background Transformational leadership is conceptualized as a set of behaviors designed to inspire, energize and motivate others to achieve higher levels of functioning, and is associated with salient health-related outcomes in organizational settings. Given (a) the similarities that exist between leadership within organizational settings and parenting within families, and (b) the importance of the family environment in the promotion of adolescent health-enhancing behaviors, the purpose of this exploratory study was to examine the cross-sectional relationships between parents’ transformational leadership behaviors and adolescent dietary and physical activity behaviors. Methods 857 adolescents (aged 13–15, mean age = 14.70 yrs) completed measures of transformational parenting behaviors, healthful dietary intake and leisure-time physical activity. Regression analyses were conducted to examine relationships between family transformational leadership and adolescent health outcomes. A further ‘extreme group analysis’ was conducted by clustering families based on quartile splits. A MANCOVA (controlling for child gender) was conducted to examine differences between families displaying (a) HIGH levels of transformational parenting (consistent HIGH TP), (b) LOW levels of transformational parenting (consistent LOW TP), and (c) inconsistent levels of transformational parenting (inconsistent HIGH-LOW TP). Results Results revealed that adolescents’ perceptions of family transformational parenting were associated with both healthy dietary intake and physical activity. Adolescents who perceived their families to display the highest levels of transformational parenting (HIGH TP group) displayed greater healthy eating and physical activity behaviors than adolescents who perceived their families to display the lowest levels of transformational parenting behaviors (LOW TP group). Adolescents who perceived their families to display inconsistent levels of transformational parenting behaviors (HIGH-LOW TP group) displayed the same levels of healthy eating behaviors as those adolescents from the LOW TP group. For physical activity behaviors, adolescents who perceived their families to display inconsistent levels of transformational parenting behaviors (HIGH-LOW TP group) did not differ in terms of physical activity than those in either the HIGH TP or LOW TP group. Conclusions Family transformational parenting behaviors were positively associated with both healthful dietary intake and leisure-time physical activity levels amongst adolescents. The findings suggest that transformational leadership theory is a useful framework for understanding the relationship between family leadership behaviors and adolescent health outcomes. PMID:22546151

Statistical modeling to determine sources of variability in exposures to welding fumes.

PubMed

Liu, Sa; Hammond, S Katharine; Rappaport, Stephen M

2011-04-01

Exposures to total particulate matter (TP) and manganese (Mn) received by workers during welding and allied hot processes were analyzed to assess the sources and magnitudes of variability. Compilation of data from several countries identified 2065 TP and 697 Mn measurements for analysis. Linear mixed models were used to determine fixed effects due to different countries, industries and trades, process characteristics, and the sampling regimen, and to estimate components of variance within workers (both intraday and interday), between workers (within worksites), and across worksites. The fixed effects explained 55 and 49% of variation in TP and Mn exposures, respectively. The country, industry/trade, type of ventilation, and type of work/welding process were the major factors affecting exposures to both agents. Measurements in the USA were generally higher than those in other countries. Exposure to TP was 67% higher in enclosed spaces and 43% lower with local exhaust ventilation (LEV), was higher among boilermakers and was higher when either a mild-steel base metal or a flux cored consumable was used. Exposure to Mn was 750% higher in enclosed spaces and 67% lower when LEV was present. Air concentrations of Mn were significantly affected by the welding consumables but not by the base metal. Resistance welding produced significantly lower TP and Mn exposures compared to other welding processes. Interestingly, exposures to TP had not changed over the 40 years of observation, while those of Mn showed (non-significant) reductions of 3.6% year(-1). After controlling for fixed effects, variance components between worksites and between-individual workers within a worksite were reduced by 89 and 57% for TP and 75 and 63% for Mn, respectively. The within-worker variation (sum of intraday and interday variance components) of Mn exposure was three times higher than that of TP exposure. The estimated probabilities of exceeding occupational exposure limits were very high (generally much >10%) for both agents. Welding exposures to TP and Mn vary considerably across the world and across occupational groups. Exposures to both contaminants have been and continue to be unacceptably high in most sectors of industry. Because exposures to the two agents have different sources and characteristics, separate control strategies should be considered to reduce welders' exposures to TP and Mn.

[Spatial variation of soil phosphorus in flooded area of the Yellow River based on GIS and geo-statistical methods: A case study in Zhoukou City, Henan, China.

PubMed

Jia, Zhen Yu; Zhang, Jun Hua; Ding, Sheng Yan; Feng, Shu; Xiong, Xiao Bo; Liang, Guo Fu

2016-04-22

Soil phosphorus is an important indicator to measure the soil fertility, because the content of soil phosphorus has an important effect on physical and chemical properties of soil, plant growth, and microbial activity in soil. In this study, the soil samples collecting and indoor analysis were conducted in Zhoukou City located in the flooded area of the Yellow River. By using GIS combined with geo-statistics, we tried to analyze the spatial variability and content distribution of soil total phosphorus (TP) and soil available phosphorus (AP) in the study area. Results showed that TP and AP of both soil layers (0-20 cm and 20-40 cm) were rich, and the contents of TP and AP in surface layer (0-20 cm) were higher than in the second layer (20-40 cm). TP and AP of both soil layers exhibited variation at medium level, and AP had varied much higher than TP. TP of both layers showed medium degree of anisotropy which could be well modeled by the Gaussian model. TP in the surface layer showed strong spatial correlation, but that of the second layer had medium spatial correlation. AP of both layers had a weaker scope in anisotropy which could be simulated by linear model, and both soil layers showed weaker spatial correlations. TP of both soil layers showed a slowly rising change from southwest to northeast of the study area, while it gradually declined from northwest to southeast. AP in soil surface layer exhibited an increase tendency firstly and then decrease from southwest to the northeast, while it decreased firstly and then increased from southeast to the northwest. AP in the second soil layer had an opposite change in the southwest to the northeast, while it showed continuously increasing tendency from northwest to the southeast. The contents of TP and AP in the surface layer presented high grades and the second layer of TP belonged to medium grade, but the second layer of AP was in a lower grade. The artificial factors such as land use type, cropping system, irrigation and fertilization were the main factors influencing the distribution and spatial variation of soil phosphorus in this area.

Family leadership styles and adolescent dietary and physical activity behaviors: a cross-sectional study.

PubMed

Morton, Katie L; Wilson, Alexandra H; Perlmutter, Lisa S; Beauchamp, Mark R

2012-04-30

Transformational leadership is conceptualized as a set of behaviors designed to inspire, energize and motivate others to achieve higher levels of functioning, and is associated with salient health-related outcomes in organizational settings. Given (a) the similarities that exist between leadership within organizational settings and parenting within families, and (b) the importance of the family environment in the promotion of adolescent health-enhancing behaviors, the purpose of this exploratory study was to examine the cross-sectional relationships between parents' transformational leadership behaviors and adolescent dietary and physical activity behaviors. 857 adolescents (aged 13-15, mean age = 14.70 yrs) completed measures of transformational parenting behaviors, healthful dietary intake and leisure-time physical activity. Regression analyses were conducted to examine relationships between family transformational leadership and adolescent health outcomes. A further 'extreme group analysis' was conducted by clustering families based on quartile splits. A MANCOVA (controlling for child gender) was conducted to examine differences between families displaying (a) HIGH levels of transformational parenting (consistent HIGH TP), (b) LOW levels of transformational parenting (consistent LOW TP), and (c) inconsistent levels of transformational parenting (inconsistent HIGH-LOW TP). Results revealed that adolescents' perceptions of family transformational parenting were associated with both healthy dietary intake and physical activity. Adolescents who perceived their families to display the highest levels of transformational parenting (HIGH TP group) displayed greater healthy eating and physical activity behaviors than adolescents who perceived their families to display the lowest levels of transformational parenting behaviors (LOW TP group). Adolescents who perceived their families to display inconsistent levels of transformational parenting behaviors (HIGH-LOW TP group) displayed the same levels of healthy eating behaviors as those adolescents from the LOW TP group. For physical activity behaviors, adolescents who perceived their families to display inconsistent levels of transformational parenting behaviors (HIGH-LOW TP group) did not differ in terms of physical activity than those in either the HIGH TP or LOW TP group. Family transformational parenting behaviors were positively associated with both healthful dietary intake and leisure-time physical activity levels amongst adolescents. The findings suggest that transformational leadership theory is a useful framework for understanding the relationship between family leadership behaviors and adolescent health outcomes.

THE INSIDIOUS BOOSTING OF THERMALLY PULSING ASYMPTOTIC GIANT BRANCH STARS IN INTERMEDIATE-AGE MAGELLANIC CLOUD CLUSTERS

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

Girardi, Léo; Marigo, Paola; Bressan, Alessandro

2013-11-10

In the recent controversy about the role of thermally pulsing asymptotic giant branch (TP-AGB) stars in evolutionary population synthesis (EPS) models of galaxies, one particular aspect is puzzling: TP-AGB models aimed at reproducing the lifetimes and integrated fluxes of the TP-AGB phase in Magellanic Cloud (MC) clusters, when incorporated into EPS models, are found to overestimate, to various extents, the TP-AGB contribution in resolved star counts and integrated spectra of galaxies. In this paper, we call attention to a particular evolutionary aspect, linked to the physics of stellar interiors, that in all probability is the main cause of this conundrum.more » As soon as stellar populations intercept the ages at which red giant branch stars first appear, a sudden and abrupt change in the lifetime of the core He-burning phase causes a temporary 'boost' in the production rate of subsequent evolutionary phases, including the TP-AGB. For a timespan of about 0.1 Gyr, triple TP-AGB branches develop at slightly different initial masses, causing their frequency and contribution to the integrated luminosity of the stellar population to increase by a factor of ∼2. The boost occurs for turn-off masses of ∼1.75 M{sub ☉}, just in the proximity of the expected peak in the TP-AGB lifetimes (for MC metallicities), and for ages of ∼1.6 Gyr. Coincidently, this relatively narrow age interval happens to contain the few very massive MC clusters that host most of the TP-AGB stars used to constrain stellar evolution and EPS models. This concomitance makes the AGB-boosting particularly insidious in the context of present EPS models. As we discuss in this paper, the identification of this evolutionary effect brings about three main consequences. First, we claim that present estimates of the TP-AGB contribution to the integrated light of galaxies derived from MC clusters are biased toward too large values. Second, the relative TP-AGB contribution of single-burst populations falling in this critical age range cannot be accurately derived by approximations such as the fuel consumption theorem, which ignore, by construction, the above evolutionary effect. Third, a careful revision of AGB star populations in intermediate-age MC clusters is urgently demanded, promisingly with the aid of detailed sets of stellar isochrones.« less

Pilot-scale comparison of four duckweed strains from different genera for potential application in nutrient recovery from wastewater and valuable biomass production.

PubMed

Zhao, Y; Fang, Y; Jin, Y; Huang, J; Bao, S; Fu, T; He, Z; Wang, F; Wang, M; Zhao, H

2015-01-01

The application potential of four duckweed strains from four genera, Wolffia globosa 0222, Lemna japonica 0223, Landoltia punctata 0224 and Spirodela polyrhiza 0225, were compared in four parallel pilot-scale wastewater treatment systems for more than 1 year. The results indicated that each duckweed strain had unique potential advantages. Unlike L. japonica 0223 and La. punctata 0224, which grow throughout the year, S. polyrhiza 0225 and W. globosa 0222 do not survive cold weather. For year round performance, L. japonica 0223 was best not only in dry biomass production (6.10 g·m(-2) ·day(-1) ), but also in crude protein (35.50%), total amino acid (26.83%) and phosphorus (1.38%) content, plus recovery rates of total nitrogen (TN), total phosphorus (TP) and CO2 (0.31, 0.085 and 7.76 g·m(-2) ·day(-1) , respectively) and removal rates of TN and TP (0.66 and 0.089 g·m(-2) ·day(-1) , respectively). This strongly demonstrates that L. japonica 0223 performed best in wastewater treatment and protein biomass production. Under nutrient starvation conditions, La. punctata 0224 had the highest starch content (45.84%), dry biomass production (4.81 g·m(-2) ·day(-1) ) and starch accumulation (2.9 g·m(-2) ·day(-1) ), making it best for starch biomass production. W. globosa 0222 and S. polyrhiza 0225 showed increased flavonoid biomass production, with higher total flavonoid content (5.85% and 4.22%, respectively) and high dominant flavonoids (>60%). This study provides useful information for selecting the appropriate local duckweed strains for further application in wastewater treatment and valuable biomass production. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

The microbial community in decaying fallen logs varies with critical period in an alpine forest.

PubMed

Chang, Chenhui; Wu, Fuzhong; Yang, Wanqin; Xu, Zhenfeng; Cao, Rui; He, Wei; Tan, Bo; Justine, Meta Francis

2017-01-01

Little information has been available on the shifts in the microbial community in decaying fallen logs during critical periods in cold forests. Minjiang fir (Abies faxoniana) fallen logs in decay classes I-V were in situ incubated on the forest floor of an alpine forest in the eastern Tibet Plateau. The microbial community was investigated during the seasonal snow cover period (SP), snow thawing period (TP), early growing season (EG) and late growing season (LG) using Phosphorous Lipid Fatty Acid (PLFA) analysis. Total microbial biomass and microbial diversity in fallen logs were much more affected by critical period than decay class, whereas decay class had a stronger effect on microbial diversity than on microbial biomass. Abundant microbial biomass and microbial diversity in logs even without the cover of snow were observed in winter, which could not be linked to thermal insulation by snow cover. The freshly decayed logs functioned as an excellent buffer of environmental variation for microbial organisms during the sharp fluctuations in temperature in winter. We also found distinct decay patterns along with seasonality for heartwood, sapwood and bark, which requires further detailed research. Gram- bacteria mainly dominated the shifts in microbial community composition from SP to EG, while fungi and Gram+ bacteria mainly dominated it from SP to TP. Based on previous work and the present study, we conclude that fallen logs on the forest floor alter ecological processes by influencing microbial communities on woody debris and beneath the soil and litter. Our study also emphasizes the need to maintain a number of fallen logs, especially fresh ones, on the forest floor.

The microbial community in decaying fallen logs varies with critical period in an alpine forest

PubMed Central

Chang, Chenhui; Wu, Fuzhong; Xu, Zhenfeng; Cao, Rui; He, Wei; Tan, Bo; Justine, Meta Francis

2017-01-01

Little information has been available on the shifts in the microbial community in decaying fallen logs during critical periods in cold forests. Minjiang fir (Abies faxoniana) fallen logs in decay classes I-V were in situ incubated on the forest floor of an alpine forest in the eastern Tibet Plateau. The microbial community was investigated during the seasonal snow cover period (SP), snow thawing period (TP), early growing season (EG) and late growing season (LG) using Phosphorous Lipid Fatty Acid (PLFA) analysis. Total microbial biomass and microbial diversity in fallen logs were much more affected by critical period than decay class, whereas decay class had a stronger effect on microbial diversity than on microbial biomass. Abundant microbial biomass and microbial diversity in logs even without the cover of snow were observed in winter, which could not be linked to thermal insulation by snow cover. The freshly decayed logs functioned as an excellent buffer of environmental variation for microbial organisms during the sharp fluctuations in temperature in winter. We also found distinct decay patterns along with seasonality for heartwood, sapwood and bark, which requires further detailed research. Gram- bacteria mainly dominated the shifts in microbial community composition from SP to EG, while fungi and Gram+ bacteria mainly dominated it from SP to TP. Based on previous work and the present study, we conclude that fallen logs on the forest floor alter ecological processes by influencing microbial communities on woody debris and beneath the soil and litter. Our study also emphasizes the need to maintain a number of fallen logs, especially fresh ones, on the forest floor. PMID:28787465

Effects of seasonal anoxia on the distribution of phosphorus fractions in the surface sediments of southeastern Arabian Sea shelf

NASA Astrophysics Data System (ADS)

Sudheesh, V.; Movitha, M.; Hatha, A. A. Mohamed; Renjith, K. R.; Resmi, P.; Rahiman, Mujeeb; Nair, S. M.

2017-11-01

The seasonal upwelling along the southeastern Arabian Sea (SEAS) brings cold, nutrient-rich low oxygen subsurface water to the continental shelf. The subsurface oxygen deficiency due to upwelling is severe in some years, the intensity of which could profoundly influence the nutrient cycling along the SEAS. Herein, we studied the effect of seasonal anoxia on fractionation of phosphorus during the peak upwelling period of August 2013. Abundance of five fractions of phosphorus (P), namely exchangeable or loosely sorbed P (Pads), iron-bound P (PFe), authigenic P (Paut), detrital apatite plus other inorganic P (Pdet) and organic P (Porg), in surface sediments of SEAS shelf has been studied using a sequential extraction procedure (SEDEX) to examine their distributions and sources. Total P (TP) concentrations ranged from 209 to 1081 μg g-1 with an average of 508 ± 256 μg g-1. Among the five P fractions, the authigenic P was the dominant species, representing about 60% of TP. The relative abundance of P fractions was in the order: Paut>Pdet>Porg>PFe> Pads. Multivariate analyses revealed that the P fractions were primarily associated with the organic constituents and fine sediments. The hypoxic bottom condition associated with summer monsoon upwelling significantly reduced the concentrations of PFe, Pads and Porg in the surface sediments. The enhanced release of organic bound and iron oxides bound P under low oxygen condition was evident from the enhanced C/P and N/P ratios and lower C/N ratio in the sediments. The intense biomineralization of organic matter and reduction of Fe-Mn oxides due to the periodic anoxia resulted in the transformations of their associated P fractions and enhanced accumulation as authigenic calcium phosphate mineral.

Classification of TP53 mutations and HPV predict survival in advanced larynx cancer.

PubMed

Scheel, Adam; Bellile, Emily; McHugh, Jonathan B; Walline, Heather M; Prince, Mark E; Urba, Susan; Wolf, Gregory T; Eisbruch, Avraham; Worden, Francis; Carey, Thomas E; Bradford, Carol

2016-09-01

Assess tumor suppressor p53 (TP53) functional mutations in the context of other biomarkers in advanced larynx cancer. Prospective analysis of pretreatment tumor TP53, human papillomavirus (HPV), Bcl-xL, and cyclin D1 status in stage III and IV larynx cancer patients in a clinical trial. TP53 exons 4 through 9 from 58 tumors were sequenced. Mutations were grouped using three classifications based on their expected function. Each functional group was analyzed for response to induction chemotherapy, time to surgery, survival, HPV status, p16INK4a, Bcl-xl, and cyclin D1 expression. TP53 mutations were found in 22 of 58 (37.9%) patients with advanced larynx cancer, including missense mutations in 13 of 58 (22.4%) patients, nonsense mutations in four of 58 (6.9%), and deletions in five of 58 (8.6%). High-risk HPV was found in 20 of 52 (38.5%) tumors. A classification based on Evolutionary Action score of p53 (EAp53) distinguished missense mutations with high risk for decreased survival from low-risk mutations (P = 0.0315). A model including this TP53 classification, HPV status, cyclin D1, and Bcl-xL staining significantly predicts survival (P = 0.0017). EAp53 functional classification of TP53 mutants and biomarkers predict survival in advanced larynx cancer. NA. Laryngoscope, 126:E292-E299, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Bilateral Hippocampal Dysfunction in Schizophrenia

PubMed Central

Hanlon, Faith M.; Houck, Jon M.; Pyeatt, Clinton J.; Lundy, S. Laura; Euler, Matthew J.; Weisend, Michael P.; Thoma, Robert J.; Bustillo, Juan R.; Miller, Gregory A.; Tesche, Claudia D.

2014-01-01

The hippocampus has long been known to be important for memory, with the right hippocampus particularly implicated in nonverbal/visuo-spatial memory and left in verbal/narrative or episodic memory. Despite this hypothesized lateralized functional difference, there has not been a single task that has been shown to activate both the right and left hippocampus differentially, dissociating the two, using neuroimaging. The transverse patterning (TP) task is a strong candidate for this purpose, as it has been shown in human and nonhuman animal studies to theoretically and empirically depend on the hippocampus. In TP, participants choose between stimuli presented in pairs, with the correct choice being a function of the specific pairing. In this project, TP was used to assess lateralized hippocampal function by varying its dependence on verbal material, with the goal of dissociating the two hippocampi. Magnetoencephalographic (MEG) data were collected while controls performed verbal and nonverbal versions of TP in order to verify and validate lateralized activation within the hippocampi. Schizophrenia patients were evaluated to determine whether they exhibited a lateralized hippocampal deficit. As hypothesized, patients’ mean level of behavioral performance was poorer than controls’ on both verbal and nonverbal TP. In contrast, patients had no decrement in performance on a verbal and nonverbal non-hippocampal-dependent matched control task. Also, controls but not patients showed more right hippocampal activation during nonverbal TP and more left hippocampal activation during verbal TP. These data demonstrate the capacity to assess lateralized hippocampal function and suggest a bilateral hippocampal behavioral and activation deficit in schizophrenia. PMID:21763438

Strong enhancement effect of silver nanowires on fluorescent property of Eu3+-ligand complexes and desired fluorescent iPP composite materials

NASA Astrophysics Data System (ADS)

Zhang, Yu; Wang, Xinzhi; Tang, Jianguo; Wang, Wei; Wang, Jinping; Belfiore, Laurence A.

2017-04-01

In this contribution, we obtained the strong enhancement effect of silver nanowires(AgNWs) on fluorescent property of Eu3+-antenna complexes through the function of the surface plasmon resonance(SPR) effect. The key structural characteristics are: (1) AgNWs are covered by the Eu3+-ligand complex and spaced by SiO2 nano-layer between AgNWs and Eu3+-ligand complex (this structure is marked as AgNWs@SiO2@EuTP), and (2) AgNWs as nano-material with large ratio of length to diameter show their good dispersion and processability in isotactic polypropylene (iPP). We obtained the important data about the optimal spacer thickness of SiO2 is 15 nm that was not found in previous publications. The enhanced intensity of fluorescence of EuTP by AgNWs in AgNWs@SiO2@EuTP is 9 times compared with that of EuTP. All of these outstanding properties and fine structures were characterized by TEM, FT-IR, XRD, and fluorescence spectrophotometer. On the other hand, the desired fluorescent iPP composite material was obtained through blending AgNWs@SiO2@EuTP into iPP host. Very importantly, the enhancement effect of AgNWs on EuTP fluorescence in AgNWs@SiO2@EuTP is refrained from the quenching caused by host polymer of iPP.

Fast focus-scanning head in two-photon photoacoustic microscopy with electrically controlled liquid lens

NASA Astrophysics Data System (ADS)

Yamaoka, Yoshihisa; Kimura, Yuka; Harada, Yoshinori; Takamatsu, Tetsuro; Takahashi, Eiji

2018-02-01

Conventional one-photon photoacoustic microscopy (PAM) utilizes high-frequency components of generated photoacoustic waves to improve the depth resolution. However, to obtain optically-high resolution in PAM in the depth direction, the use of high-frequency ultrasonic waves is to be avoided. It is because that the propagation distance is shortened as the frequency of ultrasonic waves becomes high. To overcome this drawback, we have proposed and developed two-photon photoacoustic microscopy (TP-PAM). Two-photon absorption occurs only at the focus point. TPPAM does not need to use the high-frequency components of photoacoustic waves. Thus, TP-PAM can improve the penetration depth while preserving the spatial resolution. However, the image acquisition time of TP-PAM is longer than that of conventional PAM, because TP-PAM needs to scan the laser spot both in the depth and transverse directions to obtain cross-sectional images. In this paper, we have introduced a focus-tunable electrically-controlled liquid lens in TP-PAM. Instead of a mechanical stepping-motor stage, we employed electrically-controlled liquid lens so that the depth of the focus spot can be quickly changed. In our system, the imaging speed of TP-PAM using the liquid lens and one-axis stepping-motor stage was 10 times faster than that using a two-axis stepping-motor stage only. TP-PAM with focus-scanning head consisting of the liquid lens and stepping-motor stage will be a promising method to investigate the inside of living tissues.

Karyotypic complexity rather than chromosome 8 abnormalities aggravates the outcome of chronic lymphocytic leukemia patients with TP53 aberrations

PubMed Central

Blanco, Gonzalo; Puiggros, Anna; Baliakas, Panagiotis; Athanasiadou, Anastasia; García-Malo, MªDolores; Collado, Rosa; Xochelli, Aliki; Rodríguez-Rivera, María; Ortega, Margarita; Calasanz, Mª José; Luño, Elisa; Vargas, MªTeresa; Grau, Javier; Martínez-Laperche, Carolina; Valiente, Alberto; Cervera, José; Anagnostopoulos, Achilles; Gimeno, Eva; Abella, Eugènia; Stalika, Evangelia; Hernández-Rivas, Jesús Mª; Ortuño, Francisco José; Robles, Diego; Ferrer, Ana; Ivars, David; González, Marcos; Bosch, Francesc; Abrisqueta, Pau; Stamatopoulos, Kostas; Espinet, Blanca

2016-01-01

Patients with chronic lymphocytic leukemia (CLL) harboring TP53 aberrations (TP53abs; chromosome 17p deletion and/or TP53 mutation) exhibit an unfavorable clinical outcome. Chromosome 8 abnormalities, namely losses of 8p (8p−) and gains of 8q (8q+) have been suggested to aggravate the outcome of patients with TP53abs. However, the reported series were small, thus hindering definitive conclusions. To gain insight into this issue, we assessed a series of 101 CLL patients harboring TP53 disruption. The frequency of 8p− and 8q+ was 14.7% and 17.8% respectively. Both were associated with a significantly (P < 0.05) higher incidence of a complex karyotype (CK, ≥3 abnormalities) detected by chromosome banding analysis (CBA) compared to cases with normal 8p (N-8p) and 8q (N-8q), respectively. In univariate analysis for 10-year overall survival (OS), 8p− (P = 0.002), 8q+ (P = 0.012) and CK (P = 0.009) were associated with shorter OS. However, in multivariate analysis only CK (HR = 2.47, P = 0.027) maintained independent significance, being associated with a dismal outcome regardless of chromosome 8 abnormalities. In conclusion, our results highlight the association of chromosome 8 abnormalities with CK amongst CLL patients with TP53abs, while also revealing that CK can further aggravate the prognosis of this aggressive subgroup. PMID:27821812

Long-term survivors of pancreatic adenocarcinoma show low rates of genetic alterations in KRAS, TP53 and SMAD4.

PubMed

Masetti, Michele; Acquaviva, Giorgia; Visani, Michela; Tallini, Giovanni; Fornelli, Adele; Ragazzi, Moira; Vasuri, Francesco; Grifoni, Daniela; Di Giacomo, Simone; Fiorino, Sirio; Lombardi, Raffaele; Tuminati, David; Ravaioli, Matteo; Fabbri, Carlo; Bacchi-Reggiani, Maria Letizia; Pession, Annalisa; Jovine, Elio; de Biase, Dario

2018-02-06

Pancreatic adenocarcinoma (PDAC) is one of the deadliest human malignancies. Although surgery is currently the only effective treatment for PDAC, most patients survive less than 20 months after tumor resection. The primary goal was to investigate alterations in KRAS, TP53, SMAD4 and CDKN2A/p16 in tumors from patients with exceptionally long survival after surgery. Tumors from 15 patients with PDAC that survived more than 55 months after surgery ("LS") were analyzed for KRAS, TP53, IDH1, NRAS and BRAF using next-generation sequencing. SMAD4 and CDKN2A/p16 was tested using immunohistochemistry. MGMT promoter methylation was investigated. Tumors from "LS" have a lower prevalence of KRAS and TP53 mutations and had more frequently SMAD4 retained expression, if compared with that of patients died within 24 months from surgery. The survival of patients with wild-type KRAS and TP53 tumors was more than twice longer than that of patients bearing KRAS and TP53 mutations (90.2 vs. 41.1 months). Patients with KRAS wild-type tumors and that retained SMAD4 expression had a survival twice longer than cases with alterations in both genes (83.8 vs. 36.7 months). Eleven tumors (39.3%) showed MGMT methylation. Our data indicate that absence of KRAS, TP53 and SMAD4 genetic alterations may identify a subset of pancreatic carcinomas with better outcome.

Quality of Vegetables Based on Total Phenolic Concentration Is Lower in More Rural Consumer Food Environments in a Rural American State.

PubMed

Ahmed, Selena; Byker Shanks, Carmen

2017-08-17

While daily consumption of fruits and vegetables (FVs) is widely recognized to be associated with supporting nutrition and health, disparities exist in consumer food environments regarding access to high-quality produce based on location. The purpose of this study was to evaluate FV quality using total phenolic (TP) scores (a phytochemical measure for health-promoting attributes, flavor, appearance, and shelf-life) in consumer food environments along a rural to urban continuum in the rural state of Montana, United States. Significant differences were found in the means of the FV TP scores ( p < 0.0001) and vegetable TP scores ( p < 0.0001) on the basis of rurality, while no significant difference was found for fruit TP scores by rurality ( p < 0.2158). Specifically, FV TP scores and vegetable TP scores were highest for the least rural stores and lowest for the most rural stores. Results indicate an access gap to high-quality vegetables in more rural and more health-disparate consumer food environments of Montana compared to urban food environments. Findings highlight that food and nutrition interventions should aim to increase vegetable quality in rural consumer food environments in the state of Montana towards enhancing dietary quality and food choices. Future studies are called for that examine TP scores of a wide range of FVs in diverse food environments globally. Studies are further needed that examine linkages between FV quality, food choices, diets, and health outcomes towards enhancing food environments for public health.