bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcription Factor YY1 Promotes Cell Proliferation by Directly Activating the Pentose Phosphate Pathway
Authors: Wu Shourong , Wang Huimin , Li Yanjun , Xie Yudan , Huang Can , Zhao Hezhao , Miyagishi Makoto , Kasim Vivi 
Published: June 2018

Abstract
Tumor cells alter their metabolism to meet their demand for macromolecules and support a high rate of proliferation as well as cope with oxidative stress. The transcription factor yin yang 1 (YY1) is upregulated in various types of tumors and is crucial for tumor cell proliferation and metastasis. However, its role in tumor cell metabolic reprogramming is poorly understood. Here, we show that YY1 alters tumor cell metabolism by activating glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the pentose phosphate pathway. By stimulating the pentose phosphate pathway, YY1 enhanced production of nucleotides and DNA synthesis, decreased intracellular reactive oxygen species levels, and promoted antioxidant defense by supplying increased reducing power in the form of NADPH. Importantly, YY1-mediated regulation of the pentose phosphate pathway in tumor cells occurred not through p53, but rather through direct activation of G6PD transcription by YY1. Regulation of pentose phosphate pathway activity through G6PD was strongly related to YY1-induced proliferation of tumor cells and tumorigenesis. Together, our results describe a novel role for YY1 in regulating G6PD in a p53-independent manner, which links its function in tumorigenesis to metabolic reprogramming in tumor cells.
Significance: This study reveals a novel role for YY1 in regulating G6PD and activating the pentose phosphate pathway, linking its function in tumorigenesis to metabolic reprogramming. Cancer Res; 78(16); 4549–62. ©2018 AACR.
DDX3 Activates CBC-eIF3–Mediated Translation of uORF-Containing Oncogenic mRNAs to Promote Metastasis in HNSCC
Authors: Chen Hung-Hsi , Yu Hsin-I , Yang Muh-Hwa , Tarn Woan-Yuh 
Published: June 2018

Abstract
Mutated or dysregulated DDX3 participates in the progression and metastasis of cancer via its multiple roles in regulating gene expression and cellular signaling. Here, we show that the high expression levels of DDX3 in head and neck squamous cell carcinoma (HNSCC) correlate with lymph node metastasis and poor prognosis and demonstrate that DDX3 is essential for the proliferation, invasion, and metastasis of oral squamous cell carcinoma (OSCC) cells. Microarray analyses revealed that DDX3 is required for the expression of a set of pro-metastatic genes, including ATF4-modulated genes in an aggressive OSCC cell line. DDX3 activated translation of ATF4 and a set of its downstream targets, all of which contain upstream open reading frames (uORF). DDX3 promoted translation of these targets, likely by skipping the inhibitory uORF. DDX3 specifically enhanced the association of the cap-binding complex (CBC) with uORF-containing mRNAs and facilitated recruitment of the eukaryotic initiation factor 3 (eIF3). CBC and certain eIF3 subunits contributed to the expression of metastatic-related gene expression. Taken together, our results indicate a role for the novel DDX3–CBC–eIF3 translational complex in promoting metastasis.
Significance: The discovery of DDX3-mediated expression of oncogenic uORF-containing genes expands knowledge on translational control mechanisms and provides potential targets for cancer therapy.
Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/16/4512/F1.large.jpg Cancer Res; 78(16); 4512–23. ©2018 AACR.
Experimental Lung Metastases in Mice Are More Effectively Inhibited by Blockade of IL23R than IL23
Authors: Yan Juming , Allen Stacey , Vijayan Dipti , Li Xian-Yang , Harjunpää Heidi , Takeda Kazuyoshi , Liu Jing , Cua Daniel J. , Smyth Mark J. , Teng Michele W.L. 
Published: June 2018

AbstractTumor-induced immunosuppression is mediated through various mechanisms including engagement of immune checkpoint receptors on effector cells, function of immunoregulatory cells such as regulatory T cells and myeloid-derived suppressor cells, and deployment of immunosuppressive cytokines such as TGFβ and IL10. IL23 is a cytokine that negatively affects antitumor immunity. In this study, we investigated whether IL23-deficient (IL23p19−/−) and IL23R-deficient (IL23R−/−) mice phenocopied each other, with respect to their tumor control. We found that IL23R−/− mice had significantly fewer lung metastases compared with IL23p19−/− mice across three different experimental lung metastasis models (B16F10, LWT1, and RM-1). Similarly, IL23R blocking antibodies were more effective than antibodies neutralizing IL23 in suppressing experimental lung metastases. The antimetastatic activity of anti-IL23R was dependent on NK cells and IFNγ but independent of CD8+ T cells, CD4+ T cells, activating Fc receptors, and IL12. Furthermore, our data suggest this increased antitumor efficacy was due to an increase in the proportion of IFNγ-producing NK cells in the lungs of B16F10 tumor-bearing mice. Anti-IL23R, but not anti-IL23p19, partially suppressed lung metastases in tumor-bearing mice neutralized for IL12p40. Collectively, our data imply that IL23R has tumor-promoting effects that are partially independent of IL23p19. Blocking IL23R may be more effective than neutralizing IL23 in the suppression of tumor metastases. Cancer Immunol Res; 6(8); 978–87. ©2018 AACR.
Does Sample Attrition Affect the Assessment of Frailty Trajectories Among Older Adults? A Joint Model Approach
Authors: Stolz Erwin , Mayerl Hannes , Rásky Éva , Freidl Wolfgang 
Published: June 2018

<b><i>Background:</i></b> Frailty constitutes an important risk factor for adverse outcomes among older adults. In longitudinal studies on frailty, selective sample attrition may threaten the validity of results. <b><i>Objective:</i></b> To assess the impact of sample attrition on frailty index trajectories and gaps related to socio-economic status (education) therein among older adults in Europe. <b><i>Methods:</i></b> A total of 64,143 observations from 21,044 respondents (50+) from the Survey of Health, Ageing and Retirement in Europe across 12 years of follow-up (2004–2015) and subject to substantial sample attrition (59%) were analysed. We compared results of a standard linear mixed model assuming missing at random (MAR) sample attrition with a joint model assuming missing not at random sample attrition. <b><i>Results:</i></b> Estimated frailty trajectories of both the mixed and joint models were identical up to an age of 80 years, above which modest underestimation occurred when a standard linear mixed model was used rather than a joint model. The latter effect was larger for men than women. Substantial education-based inequality in frailty continued throughout old age in both the mixed and joint models. <b><i>Conclusion:</i></b> Linear mixed models assuming MAR sample attrition provided good estimates of frailty trajectories up until high age. Thus, the validity of existing studies estimating frailty trajectories based on standard linear mixed models seems not threatened by substantial sample attrition.
Trabeculae in Patagonian mountain cypress (Austrocedrus chilensis) associated with Phytophthora austrocedri infection
Authors: Troncoso Oscar , Greslebin Alina 
Published: June 2018

ABSTRACTPhytophthora austrocedriis a straminipilous (heterokonta) organism that causes mortality ofAustrocedrus chilensis, an endemic Cupressaceae from the Patagonian Andes forest in temperate South America. This soil pathogen colonizes and kills the roots and extends up to the stem causing necrosis of cambium, phloem and xylem ray parenchyma. An anatomical study of affected tissues was conducted in order to better understand the process of pathogen colonization and tree response. It was found that tracheids of the xylem of affected trees showed large numbers of trabeculae, both rod- and plate-shaped. The occurrence of these structures was clearly associated with the necrotic lesion area, since the trabeculae were rare in healthy tissues above the necrotic lesion. Trabeculae occurred in a variety of arrangements: solitary or in long files, single, double or triple. Our results could indicate that trabeculae proliferation in tracheids ofA. chilensistrees is induced by the stress generated by theP. austrocedriinvasion. Whether this is triggered by a nonspecific stress response or in direct response to the pathogen remains to be tested.
A Climatology of Strong Large-Scale Ocean Evaporation Events. Part I: Identification, Global Distribution, and Associated Climate Conditions
Authors: Aemisegger Franziska , Papritz Lukas 
Published: June 2018

AbstractThis paper presents an object-based, global climatology (1979–2014) of strong large-scale ocean evaporation (SLOE) and its associated climatic properties. SLOE is diagnosed using an “atmospheric moisture uptake efficiency” criterion related to the ratio of surface evaporation and integrated water vapor content in the near-surface atmosphere. The chosen Eulerian identification procedure focuses on events that strongly contribute to the available near-surface atmospheric humidity. SLOE is particularly frequent along the warm ocean western boundary currents, downstream of large continental areas, and at the sea ice edge in polar regions with frequent cold-air outbreaks. Furthermore, wind-driven SLOE occurs in regions with topographically enforced winds. On a global annual average, SLOE occurs only 6% of the time but explains 22% of total ocean evaporation. An analysis of the past history and fate of air parcels involved in cold season SLOE in the North Atlantic and south Indian Oceans shows that cold-air advection is the main mechanism that induces these events. Extratropical cyclones thereby play an important role in setting the necessary equatorward synoptic flow. Consequently, the interannual variability of SLOE associated with the North Atlantic Oscillation and the southern annular mode reveals a very high sensitivity of SLOE with respect to the location of the storm tracks. This study highlights the strong link between transient synoptic events and the spatiotemporal variability in ocean evaporation patterns, which cannot be deduced from thermodynamic steady-state and climate mean state considerations alone.
Insights into the Zonal-Mean Response of the Hydrologic Cycle to Global Warming from a Diffusive Energy Balance Model
Authors: Siler Nicholas , Roe Gerard H. , Armour Kyle C. 
Published: June 2018

AbstractRecent studies have shown that the change in poleward energy transport under global warming is well approximated by downgradient transport of near-surface moist static energy (MSE) modulated by the spatial pattern of radiative forcing, feedbacks, and ocean heat uptake. Here we explore the implications of downgradient MSE transport for changes in the vertically integrated moisture flux and thus the zonal-mean pattern of evaporation minus precipitation (E − P). Using a conventional energy balance model that we have modified to represent the Hadley cell, we find that downgradient MSE transport implies changes in E − P that mirror those simulated by comprehensive global climate models (GCMs), including a poleward expansion of the subtropical belt where E > P, and a poleward shift in the extratropical minimum of E − P associated with the storm tracks. The surface energy budget imposes further constraints on E and P independently: E increases almost everywhere, with relatively little spatial variability, while P must increase in the deep tropics, decrease in the subtropics, and increase in middle and high latitudes. Variations in the spatial pattern of radiative forcing, feedbacks, and ocean heat uptake across GCMs modulate these basic features, accounting for much of the model spread in the zonal-mean response of E and P to climate change. Thus, the principle of downgradient energy transport appears to provide a simple explanation for the basic structure of hydrologic cycle changes in GCM simulations of global warming.
Convective Storm Life Cycle and Environments near the Sierras de Córdoba, Argentina
Authors: Mulholland Jake P. , Nesbitt Stephen W. , Trapp Robert J. , Rasmussen Kristen L. , Salio Paola V. 
Published: June 2018

AbstractSatellite observations have revealed that some of the world’s most intense deep convective storms occur near the Sierras de Córdoba, Argentina, South America. A C-band, dual-polarization Doppler weather radar recently installed in the city of Córdoba in 2015 is now providing a high-resolution radar perspective of this intense convection. Radar data from two austral spring and summer seasons (2015–17) are used to document the convective life cycle, while reanalysis data are utilized to construct storm environments across this region. Most of the storms in the region are multicellular and initiate most frequently during the early afternoon and late evening hours near and just east of the Sierras de Córdoba. Annually, the peak occurrence of these storms is during the austral summer months of December, January, and February. These Córdoba radar-based statistics are shown to be comparable to statistics derived from Tropical Rainfall Measuring Mission Precipitation Radar data. While generally similar to storm environments in the United States, storm environments in central Argentina tend to be characterized by larger CAPE and weaker low-level vertical wind shear. One of the more intriguing results is the relatively fast transition from first storms to larger mesoscale convective systems, compared with locations in the central United States.
Development of a novel fluorescent activity assay for lecithin:cholesterol acyltransferase
Authors: Sakurai Toshihiro , Sakurai Akiko , Vaisman Boris L , Nishida Takafumi , Neufeld Edward B , Demosky Stephen J , Sampson Maureen L , Shamburek Robert D , Freeman Lita A , Remaley Alan T 
Published: June 2018

Background Lecithin:cholesterol acyltransferase (LCAT) is a plasma enzyme that esterifies cholesterol. Recombinant human LCAT (rhLCAT) is now being developed as an enzyme replacement therapy for familial LCAT deficiency and as a possible treatment for acute coronary syndrome. The current ‘gold standard’ assay for LCAT activity involves the use of radioisotopes, thus making it difficult for routine clinical use. Methods We have developed a novel and more convenient LCAT activity assay using fluorescence-labelled cholesterol (BODIPY-cholesterol), which is incorporated into proteoliposomes as a substrate instead of radiolabelled cholesterol. Results The apparent Km and Vmax were 31.5  µmol/L and 55.8 nmol/h/nmoL, rhLCAT, respectively, for the 3H-cholesterol method and 103.1  µmol/L and 13.4 nmol/h/nmol rhLCAT, respectively, for the BODIPY-cholesterol method. Although the two assays differed in their absolute units of LCAT activity, there was a good correlation between the two test assays ( r = 0.849, P < 1.6 × 10−7, y = 0.1378x + 1.106). The BODIPY-cholesterol assay had an intra-assay CV of 13.7%, which was superior to the intra-assay CV of 20.8% for the radioisotopic assay. The proteoliposome substrate made with BODIPY-cholesterol was stable to storage for at least 10 months. The reference range ( n = 20) for the fluorescent LCAT activity assay was 4.6–24.1 U/mL/h in healthy subjects. Conclusions In summary, a novel fluorescent LCAT activity assay that utilizes BODIPY-cholesterol as a substrate is described that yields comparable results to the radioisotopic method.
Serum high-sensitive C-reactive protein is associated with dietary intakes in diabetic patients with and without hypertension: a cross-sectional study
Authors: Bagherniya Mohammad , Khayyatzadeh Sayyed Saeid , Heidari Bakavoli Ali reza , Ferns Gordon A , Ebrahimi Mahmoud , Safarian Mohammad , Nematy Mohsen , Ghayour-Mobarhan Majid 
Published: June 2018

Background Serum high-sensitive C-reactive protein (hs-CRP) concentrations independently predict the development of diabetes, metabolic syndrome and cardiovascular disease. However, the impact of dietary factors on serum high-sensitive C-reactive protein concentrations in diabetic patients has received limited attention. We aimed to investigate the association between dietary factors and high-sensitive C-reactive protein , among diabetic patients with and without hypertension and healthy subjects. Methods In this cross-sectional study, diabetics with ( n = 325) and without hypertension ( n = 599) and healthy individuals ( n = 1220) were recruited in Mashhad, Iran. Dietary intake was assessed by 24-h recall. Biochemical parameters including serum high-sensitive C-reactive protein were measured using standard protocols. Stepwise multiple regression analysis was used to predict whether serum high-sensitive C-reactive protein concentration was associated with dietary constituents. Results High-sensitive C-reactive protein was significantly higher among hypertensive and non-hypertensive diabetic patients compared with healthy subjects ( P < 0.001). The dietary intake of zinc + 6.4% and calcium −3.4% and body mass index +3.9% explained approximately 13.7% of the variation in serum high-sensitive C-reactive protein among diabetic hypertensive patients. Approximately 9.7% of the variation in serum high-sensitive C-reactive protein in diabetic non-hypertensive patients could be explained by body mass index, and intake of sodium, iron and cholesterol. In the healthy subjects, approximately 4.4% of the total variation in serum high-sensitive C-reactive protein concentration could be explained by cholesterol consumption and waist circumference. Conclusion Serum high-sensitive C-reactive protein concentrations were found to be a significant predictor for hypertensive and non-hypertensive diabetic subjects. There was a significant association between dietary factors include zinc, iron, sodium and cholesterol and serum high-sensitive C-reactive protein, while there was an inverse association between dietary calcium and serum high-sensitive C-reactive protein in diabetic hypertensive individuals.
Evaluation of the revised Schwartz creatinine-based glomerular filtration rate estimating equation in Black African children in KwaZulu-Natal, South Africa
Authors: Rampursat Yashna , Bhimma Rajendra , Naicker Elaene , Peer Fozy , Gounden Verena 
Published: June 2018

Background The use of serum creatinine equations for estimating glomerular filtration rate is well known in adults and children. We evaluated the revised Schwartz creatinine-based estimated glomerular filtration rate prediction equation in Black African children in KwaZulu-Natal, South Africa. Methods Review of medical records of all Black African patients aged 2–18 years old who have had glomerular filtration rate determined by intravenous Technetium-99 m-diethylene-triamine-pentaacetate, for the period 1 January 2010 to 31 December 2014 at the Inkosi Albert Luthuli Central Hospital, Durban, South Africa was performed. Estimated glomerular filtration rate result obtained using the revised Schwartz equation was compared to Technetium-99 m-diethylene-triamine-pentaacetate plasma clearance measured glomerular filtration rate. Accuracy of the estimated glomerular filtration rate equations within 10% (P10) and 30% (P30) of the measured glomerular filtration rate, sensitivity and specificity for predicting glomerular filtration rate < 60 mL/min/1.73 m2 and < 30 mL/min/1.73 m2 was determined. Results Results from 148 African children between 2 and 18 years old were analysed. P10 and P30 values were 16 and 49%, respectively. Sensitivity of 92.9% (95% CI: 80.5–85), specificity of 95.3 (95% CI: 89.3–98.5) and AUC of 0.96 (95% CI 0.92–0.99) were obtained for measured estimated glomerular filtration rate < 60 mL/min/1.73 m2. Sensitivity of 88.2% (95% CI: 63.6–98.5), specificity of 90.8 (95% CI: 84.5–95.2) and area under the curve of 0.93 (95% CI 0.88–0.96) were obtained for measured estimated glomerular filtration rate < 30 mL/min/1.73 m2. Conclusions The revised Schwartz equation did not meet the National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines of 90% of estimated glomerular filtration rate results within 30% of measured glomerular filtration rate.
Serum α-melanocyte-stimulating hormone may act as a protective biomarker for non-traumatic osteonecrosis of the femoral head
Authors: Mao Zheng , Liu Gang , Chen Jing-Jie , Liu Dan , Xu Min-Peng , Zhao Chang , Yang Hai-Tao , Yue Yong-Bin 
Published: June 2018

Background The α-melanocyte-stimulating hormone (α-MSH), an endogenous neuropeptide derived from proopiomelanocortin (POMC), has been identified to suppress inflammation and prevent osteoblast damage. Objective The present study was aimed to investigate the role of serum α-MSH in non-traumatic osteonecrosis of the femoral head (ONFH). Methods Seventy-nine patients diagnosed with non-traumatic ONFH and 79 sex- and age-matched healthy controls were enrolled in the study. Serum α-MSH concentrations were examined with a double antibody radioimmunoassay. The radiographic progression of ONFH was assessed by X-ray plain film according to the FICAT grading system. The symptomatic severity was evaluated by visual analogue scale scores, Harris hip scores and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. The serum concentrations of protective marker adiponectin and bone necrosis inflammation factor IL-33 concentrations were also examined. The receiver operating characteristic (ROC) analysis curve was performed to explore the diagnostic value of α-MSH, adiponectin and IL-33 for radiographic progression. Results Serum α-MSH concentrations were significantly lower in ONFH patients than in healthy controls. The case group included 29 non-traumatic ONFH patients with FICAT grade I/II, 27 with grade III and 23 with grade IV. ONFH patients with grade I/II had significantly higher α-MSH concentrations in serum compared with those with FICAT grades III and IV. ONFH patients with FICAT grade III showed significantly elevated concentrations of α-MSH in serum compared with those with FICAT grade IV. Serum α-MSH concentrations were negatively associated with radiographic progression by FICAT grading system, and symptomatic severity defined by visual analogue scale scores, Harris hip scores and WOMAC scores. In addition, serum α-MSH concentrations were positively related to the expression of adiponectin and negatively associated with IL-33. ROC analysis curve demonstrated that α-MSH exhibited the equal value for the diagnosis of ONFH radiographic progression compared with IL-33. Conclusions Serum α-MSH may act as a protective biomarker for non-traumatic ONFH. Systematic application of α-MSH serving as an adjunctive therapy for treating non-traumatic ONFH deserves further investigation.