bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphatase GhDsPTP3a interacts with annexin protein GhANN8b to reversely regulate salt tolerance in cotton (Gossypium spp.)
Authors: Mu Chun , Zhou Lin , Shan Libo , Li Fangjun , Li Zhaohu 
Published: April 2019

Summary

Salinity is among the major factors limiting crop production worldwide. Despite having moderate salt‐tolerance, cotton (Gossypium spp.) suffers severe yield losses to salinity stresses, largely due to being grown on saline‐alkali and dry lands.

To identify genetic determinants conferring salinity tolerance in cotton, we deployed a functional genomic screen using a cotton cDNA library in a virus‐induced gene silencing (VIGS) vector. We have revealed that silencing of GhDsPTP3a, which encodes a protein phosphatase, increases cotton tolerance to salt stress.

Yeast two‐hybrid screens indicated that GhDsPTP3a interacts with GhANN8b, an annexin protein, which plays a positive role in regulating cotton response to salinity stress. Salt stress induces GhANN8b phosphorylation, which is subsequently dephosphorylated by GhDsPTP3a. Ectopic expression of GhDsPTP3a and GhANN8b oppositely regulates plant salt tolerance and calcium influx. In addition, we have revealed that silencing of GhDsPTP3a or GhANN8b exerts opposing roles in regulating GhSOS1 transcript levels, and ectopic expression of GhANN8b elevates Na+ efflux in Arabidopsis under salinity stress.

Our study demonstrates that a cotton phosphatase GhDsPTP3a and an annexin protein GhANN8b interact and reversely modulate Ca2+ and Na+ fluxes in cotton salinity responses.
Moral Hedging and Responding to Reasons
Authors: Hicks Amelia 
Published: April 2019

AbstractIn this paper, I argue that the fetishism objection to moral hedging fails. The objection rests on areasons‐responsiveness account of moral worth, according to which an action has moral worth only if the agent is responsive to moral reasons. However, by adopting a plausible theory of non‐ideal moral reasons, one can endorse a reasons‐responsiveness account of moral worth while maintaining that moral hedging is sometimes an appropriate response to moral uncertainty. Thus, the theory of moral worth upon which the fetishism objection relies does not, in fact, support that objection.
Hyponatremia secondary to severe atopic dermatitis in early infancy
Authors: Adachi Masanori , Takamasu Tetsuya , Inuo Chisato 
Published: April 2019

AbstractBackgroundInfants with atopic dermatitis who developed hyponatremia and hyperkalemia with raised aldosterone have been repeatedly described in the Japanese‐language literature, but similar reports from other countries are scarce.MethodsWe collected reports of atopic dermatitis complicated with hyponatremia (≤130 mEq/L), written either in English or in Japanese, to delineate the characteristics and to elucidate the pathophysiology of this condition.ResultsOf a total of 36 patients, 35 were Japanese. All patients were infants younger than 9 months. Mean height SD score (SDS) at presentation was −2.1 ± 1.4 (n = 25), with mean body mass index 14.1 ± 1.7 kg/m2 (n = 28). Mean sodium was 120.7 ± 6.1 mEq/L. While 28 patients had hyperkalemia, seven patients had normokalemia. Elevated aldosterone was documented in 15 patients. Nutrition mainly with breast‐feeding (97%), parental refusal of steroid ointment (77%), and the association of hypoalbuminemia (73%) were frequent findings. Diminished urinary sodium was verified in all 12 patients tested, indicating that sodium loss from the skin exudates, with limited supply of sodium from breast milk, is the primary cause of hyponatremia. Hyperkalemia seems to result from decreased delivery of sodium to the distal nephron and from the mechanism of the so‐called “aldosterone paradox”, which inhibits potassium secretion. In addition, physiological aldosterone insensitivity during infancy, low muscle volume, and impaired Na+,K+‐ATPase function due to protein deficiency seems to exaggerate the hyperkalemia.ConclusionsHyponatremia secondary to severe atopic dermatitis is an age‐dependent manifestation, elicited by inappropriate treatment that leads to sodium loss from the damaged skin and resultant hyperkalemia via multifaceted mechanisms.
Extra‐plastidial degradation of chlorophyll and photosystem I in tobacco leaves involving ‘senescence‐associated vacuoles’
Authors: Gomez Facundo M. , Carrión Cristian A. , Costa María L. , Desel Christine , Kieselbach Thomas , Funk Christiane , Krupinska Karin , Guiamet Juan 
Published: April 2019

SummaryChlorophyll (Chl) loss is the main visible symptom of senescence in leaves. The initial steps of Chl degradation operate within the chloroplast, but the observation that ‘senescence‐associated vacuoles’ (SAVs) contain Chl raises the question of whether SAVs might also contribute to Chl breakdown. Previous confocal microscope observations (Martínez et al., 2008) showed many SAVs containing Chl. Isolated SAVs contained Chl a and b (with a Chl a/b ratio close to 5) and lower levels of chlorophyllide a. Pheophytin a and pheophorbide a were formed after the incubation of SAVs at 30°C in darkness, suggesting the presence of Chl‐degrading activities in SAVs. Chl in SAVs was bound to a number of ‘green bands’. In the most abundant green band of SAVs, Western blot analysis showed the presence of photosystem I (PSI) Chl‐binding proteins, including the PsaA protein of the PSI reaction center and the apoproteins of the light‐harvesting complexes (Lhca 1–4). This was confirmed by: (i) measurements of 77‐K fluorescence emission spectra showing a single emission peak at around 730 nm in SAVs; (ii) mass spectrometry of the most prominent green band with the slowest electrophoretic mobility; and (iii) immunofluorescence detection of PsaA in SAVs observed through confocal microscopy. Incubation of SAVs at 30°C in darkness caused a steady decrease in PsaA levels. Overall, these results indicate that SAVs may be involved in the degradation of PSI proteins and their associated chlorophylls during the senescence of leaves.
Asymmetric effects of demand uncertainty on intrafirm trade in durable and non‐durable industries
Authors: Lee Sooyoung 
Published: April 2019

AbstractThis paper unveils a new empirical regularity regarding the asymmetric patterns of international sourcing modes in the durable and non‐durable industries under uncertainty, and explains the asymmetry based on the traditional lens of the transaction cost economics. Under demand uncertainty, firms face trade‐offs between outsourcing and vertical integration: while outsourcing requires less initial investment and allows easier market entry and exit, vertical integration offers better management and communication systems. In the durable industries, consistent with the transaction cost economics, the relationship between vertical integration and uncertainty is positive. In the nondurable industries, however, such relationship is weaker because inelastic demand and shorter gaps between production and sales mitigate the effect of uncertainty. I show the asymmetric effects of uncertainty based on a simple general equilibrium model and provide consistent empirical evidence using US intrafirm trade and microeconomic uncertainty data.
Ophthalmic lesions in a population of cold‐stunned sea turtles (Chelonia mydas, Lepidochelys kempii, Caretta caretta)
Authors: Lively Melissa J. , Westermeyer Hans D. , Harms Craig A. , Christiansen Emily F. 
Published: April 2019

AbstractObjectiveTo document ocular lesions present in cold‐stunned sea turtles and determine the impact of these lesions on their release.AnimalsAll sea turtles (Caretta caretta, Chelonia mydas, and Lepidochelys kempii) presenting to rehabilitation centers in North Carolina over two cold stun seasons.ProceduresComplete ophthalmic examination using slit‐lamp biomicroscopy, fluorescein stain, rebound tonometry, and occasionally binocular indirect funduscopy was performed within 1 week of presenting to the rehabilitation centers. A second examination was performed 2 weeks after the first examination in animals with ocular lesions and still present at the center.ResultsOne hundred and sixty‐four turtles (121 Chelonia mydas, 26 Lepidochelys kempii, 17 Caretta caretta) were evaluated over two cold stun seasons (2016‐2017 and 2017‐2018). Ocular or periocular lesions were identified in 78 of 164 (47.5%) turtles examined with 37 of 164 (22.5%) having bilateral disease. The most common ocular lesion was superficial corneal ulceration, accounting for 21.3% of all lesions. Adnexal lesions were also common, while intraocular abnormalities were overall rare. Most resolved uneventfully. Though some blinding lesions were noted, these were not present bilaterally in any one turtle, and thus, ocular findings did not affect release.ConclusionOcular lesions in cold‐stunned sea turtles are common. Some of these lesions are potentially blinding or require appropriate care, so evaluation of cold‐stunned turtles should include a complete ophthalmic examination.
Separating Multiple Moving Sources by Microphone Array Signals for Wayside Acoustic Fault Diagnosis
Authors: Xiong Wei , He Qingbo , Peng Zhike 
Published: April 2019

Abstract
Wayside acoustic defective bearing detector (ADBD) system is a potential technique in ensuring the safety of traveling vehicles. However, Doppler distortion and multiple moving sources aliasing in the acquired acoustic signals decrease the accuracy of defective bearing fault diagnosis. Currently, the method of constructing time-frequency (TF) masks for source separation was limited by an empirical threshold setting. To overcome this limitation, this study proposed a dynamic Doppler multisource separation model and constructed a time domain-separating matrix (TDSM) to realize multiple moving sources separation in the time domain. The TDSM was designed with two steps of (1) constructing separating curves and time domain remapping matrix (TDRM) and (2) remapping each element of separating curves to its corresponding time according to the TDRM. Both TDSM and TDRM were driven by geometrical and motion parameters, which would be estimated by Doppler feature matching pursuit (DFMP) algorithm. After gaining the source components from the observed signals, correlation operation was carried out to estimate source signals. Moreover, fault diagnosis could be carried out by envelope spectrum analysis. Compared with the method of constructing TF masks, the proposed strategy could avoid setting thresholds empirically. Finally, the effectiveness of the proposed technique was validated by simulation and experimental cases. Results indicated the potential of this method for improving the performance of the ADBD system.
Does exercise impact gut microbiota composition in men receiving androgen deprivation therapy for prostate cancer? A single-blinded, two-armed, randomised controlled trial
Authors: Newton Robert U , Christophersen Claus T , Fairman Ciaran M , Hart Nicolas H , Taaffe Dennis R , Broadhurst David , Devine Amanda , Chee Raphael , Tang Colin I , Spry Nigel , Galvão Daniel A 
Published: April 2019

IntroductionA potential link exists between prostate cancer (PCa) disease and treatment and increased inflammatory levels from gut dysbiosis. This study aims to examine if exercise favourably alters gut microbiota in men receiving androgen deprivation therapy (ADT) for PCa. Specifically, this study will explore whether: (1) exercise improves the composition of gut microbiota and increases the abundance of bacteria associated with health promotion and (2) whether gut health correlates with favourable inflammatory status, bowel function, continence and nausea among patients participating in the exercise intervention.Methods and analysisA single-blinded, two-armed, randomised controlled trial will explore the influence of a 3-month exercise programme (3 days/week) for men with high-risk localised PCa receiving ADT. Sixty patients will be randomly assigned to either exercise intervention or usual care. The primary endpoint (gut health and function assessed via feacal samples) and secondary endpoints (self-reported quality of life via standardised questionnaires, blood biomarkers, body composition and physical fitness) will be measured at baseline and following the intervention. A variety of statistical methods will be used to understand the covariance between microbial diversity and metabolomics profile across time and intervention. An intention-to-treat approach will be utilised for the analyses with multiple imputations followed by a secondary sensitivity analysis to ensure data robustness using a complete cases approach.Ethics and disseminationEthics approval was obtained from the Human Research Ethics Committee of Edith Cowan University (ID: 19827 NEWTON). Findings will be reported in peer-reviewed publications and scientific conferences in addition to working with national support groups to translate findings for the broader community. If exercise is shown to result in favourable changes in gut microbial diversity, composition and metabolic profile, and reduce gastrointestinal complications in PCa patients receiving ADT, this study will form the basis of a future phase III trial.Trial registration numberANZCTR12618000280202.
Optimization winding design of a composites intermediate shaft
Authors: Yoon Sung-Won , Kim Tae-Yeob , Cho Je-Hyoung , Ha Jong-Rok , Kim Yun-Hae 
Published: April 2019

The purpose of this study is to determine the correct estimation of the laminate patterns for composites intermediate shaft. The laminate patterns in the filament winding process are an important factor in determining the strength and life of the final structure. In this study, the structural safety was analyzed for the laminate patterns in four cases. In addition, this work evaluated the range of laminated angles for optimal thickness selection. The laminate patterns and the order of the layers were determined by considering the results of the finite element analysis. The shear stress equation of the hollow shaft for torsional loads showed that the thickness of the structure varied with the diameter ratio. At the maximum diameter ratio (the smallest shaft thickness), the required shear strength for the structure was 36.6 MPa. Also, the most stable stress distribution was selected at [Formula: see text] to [Formula: see text]. The shear modulus according to the laminated angle was considered to give the best strength value when stacked at [Formula: see text]. The research results in this study suggest that the design of an optimized intermediate shaft of composite materials can be supplemented.
Concurrent Targeting of Glutaminolysis and Metabotropic Glutamate Receptor 1 (GRM1) Reduces Glutamate Bioavailability in GRM1+ Melanoma
Authors: Shah Raj , Singh Simar J. , Eddy Kevinn , Filipp Fabian V. , Chen Suzie 
Published: April 2019

AbstractAberrant glutamatergic signaling has been implicated in altered metabolic activity in many cancer types, including malignant melanoma. Previously, we have illustrated the role of metabotropic glutamate receptor 1 (GRM1) in neoplastic transformation of melanocytes in vitro and spontaneous metastatic melanoma in vivo. In this study, we showed that autocrine stimulation constitutively activates the GRM1 receptor and its downstream mitogenic signaling. GRM1-activated (GRM1+) melanomas exhibited significantly increased expression of glutaminase (GLS), which catalyzes the first step in the conversion of glutamine to glutamate. In cultured GRM1+ melanoma cell lines, CB-839, a potent, selective, and orally bioavailable inhibitor of GLS, suppressed cell proliferation, while riluzole, an inhibitor of glutamate release, promoted apoptotic cell death in vitro and in vivo. Combined treatment with CB-839 and riluzole treatment proved to be superior to single-agent treatment, restricting glutamate bioavailability and leading to effective suppression of tumor cell proliferation in vitro and tumor progression in vivo. Hyperactivation of GRM1 in malignant melanoma is an oncogenic driver, which acts independently of canonical melanoma proto-oncogenes, BRAF or NRAS. Overall, these results indicate that expression of GRM1 promotes a metabolic phenotype that supports increased glutamate production and autocrine glutamatergic signaling, which can be pharmacologically targeted by decreasing glutamate bioavailability and the GLS-dependent glutamine to glutamate conversion.Significance:These findings demonstrate that targeting glutaminolytic glutamate bioavailability is an effective therapeutic strategy for GRM1-activated tumors.
Cholesterol Induces Epithelial-to-Mesenchymal Transition of Prostate Cancer Cells by Suppressing Degradation of EGFR through APMAP
Authors: Jiang Siyuan , Wang Xuetong , Song Dalong , Liu XiaoJun , Gu Yinmin , Xu Zhiyuan , Wang Xiaodong , Zhang Xiaolu , Ye Qinong , Tong Zhou , Yan BingXue , Yu Jie , Chen Yunzhao , Sun Minxuan , Wang Yang , Gao Shan 
Published: April 2019

Abstract

Cholesterol increases the risk of aggressive prostate cancer and has emerged as a potential therapeutic target for prostate cancer. The functional roles of cholesterol in prostate cancer metastasis are not fully understood. Here, we found that cholesterol induces the epithelial-to-mesenchymal transition (EMT) through extracellular-regulated protein kinases 1/2 pathway activation, which is mediated by EGFR and adipocyte plasma membrane-associated protein (APMAP) accumulation in cholesterol-induced lipid rafts. Mechanistically, APMAP increases the interaction with EGFR substrate 15-related protein (EPS15R) to inhibit the endocytosis of EGFR by cholesterol, thus promoting cholesterol-induced EMT. Both the mRNA and protein levels of APMAP are upregulated in clinical prostate cancer samples. Together, these findings shed light onto an APMAP/EPS15R/EGFR axis that mediates cholesterol-induced EMT of prostate cancer cells.

Significance:
This study delineates the molecular mechanisms by which cholesterol increases prostate cancer progression and demonstrates that the binding of cholesterol-induced APMAP with EPS15R inhibits EGFR internalization and activates ERK1/2 to promote EMT.
HDAC8 Regulates a Stress Response Pathway in Melanoma to Mediate Escape from BRAF Inhibitor Therapy
Authors: Emmons Michael F. , Faião-Flores Fernanda , Sharma Ritin , Thapa Ram , Messina Jane L. , Becker Jurgen C. , Schadendorf Dirk , Seto Edward , Sondak Vernon K. , Koomen John M. , Chen Yian A. , Lau Eric K. , Wan Lixin , Licht Jonathan D. , Smalley Keiran S.M. 
Published: April 2019

Abstract

Melanoma cells have the ability to switch to a dedifferentiated, invasive phenotype in response to multiple stimuli. Here, we show that exposure of melanomas to multiple stresses including BRAF–MEK inhibitor therapy, hypoxia, and UV irradiation leads to an increase in histone deacetylase 8 (HDAC8) activity and the adoption of a drug-resistant phenotype. Mass spectrometry–based phosphoproteomics implicated HDAC8 in the regulation of MAPK and AP-1 signaling. Introduction of HDAC8 into drug-naïve melanoma cells conveyed resistance both in vitro and in vivo. HDAC8-mediated BRAF inhibitor resistance was mediated via receptor tyrosine kinase activation, leading to MAPK signaling. Although HDACs function at the histone level, they also regulate nonhistone substrates, and introduction of HDAC8 decreased the acetylation of c-Jun, increasing its transcriptional activity and enriching for an AP-1 gene signature. Mutation of the putative c-Jun acetylation site at lysine 273 increased transcriptional activation of c-Jun in melanoma cells and conveyed resistance to BRAF inhibition. In vivo xenograft studies confirmed the key role of HDAC8 in therapeutic adaptation, with both nonselective and HDAC8-specific inhibitors enhancing the durability of BRAF inhibitor therapy. Our studies demonstrate that HDAC8-specific inhibitors limit the adaptation of melanoma cells to multiple stresses including BRAF–MEK inhibition.

Significance:
This study provides evidence that HDAC8 drives transcriptional plasticity in melanoma cells in response to a range of stresses through direct deacetylation of c-Jun.
Identification of Novel Circulating miRNA Biomarkers for the Diagnosis of Esophageal Squamous Cell Carcinoma and Squamous Dysplasia
Authors: Shen Yi , Ding Yuanjie , Ma Qing , Zhao Lei , Guo Xudong , Shao Yi , Niu Chen , He Yan , Zhang Feng , Zheng Deqiang , Wei Wenqiang , Liu Fen 
Published: April 2019

Abstract

Background:
Circulating miRNAs have been identified as diagnostic biomarkers for esophageal squamous cell carcinoma (ESCC), but their efficacy in discovering early-stage ESCC is still unsatisfying. Esophageal squamous dysplasia (ESD) is the precursor lesion of ESCC. Notably, little is known about the role(s) of circulating miRNAs in identifying ESD. In this study, we, therefore, aimed to identify serum miRNAs as novel diagnostic markers for detecting ESD and ESCC.

Methods:
The genome-wide miRNA expression was profiled in 104 (52 ESCC and 52 controls) serum samples using microarray. Seven candidate miRNAs from the microarray assay were evaluated for their diagnostic performance in another cohort of 266 participants (96 ESCC, 92 ESD, and 78 healthy controls).

Results:
The serum levels of miR-16-5p, miR-197-5p, miR-451a, and miR-92a-3p were associated with ESCC; the biomarker based on the panel of these four miRNAs could efficiently distinguish patients with ESCC from the controls [AUC = 0.856; 95% confidence interval (CI), 0.794–0.905; P &lt; 0.001]. The serum levels of miR-16-5p, miR-320c, miR-638, and miR-92a-3p were significantly higher in patients with ESD than in controls, and this four-miRNA signature could efficiently differentiate patients with ESD from the controls (AUC = 0.842; 95% CI, 0.778–0.893; P &lt; 0.001). In addition, compared with serum carcinoembryonic antigen and carbohydrate antigen 199, miRNA-based panels had a better diagnostic performance in distinguishing patients with ESCC and ESD from healthy controls.

Conclusions:
Our study identified two novel panels of circulating miRNAs with high efficiency in detecting ESCC and ESD, suggesting that circulating miRNAs, in particular the combination of them, might serve as noninvasive biomarkers for the early detection of ESCC.

Impact:
This study suggests the feasibility of using circular miRNA-based blood tests to aid in the detection of ESD and ESCC.
Tumor-Derived α-Fetoprotein Suppresses Fatty Acid Metabolism and Oxidative Phosphorylation in Dendritic Cells
Authors: Santos Patricia M. , Menk Ashley V. , Shi Jian , Tsung Allan , Delgoffe Greg M. , Butterfield Lisa H. 
Published: April 2019

Abstract
Cellular metabolism supports immune cell function. Here, we identify a reduction in fatty acid synthesis and mitochondrial metabolism in dendritic cells (DC) due to α-fetoprotein (AFP), a protein secreted by hepatocellular cancer (HCC). DCs cultured in the presence of AFP show reduced expression of the metabolic regulatory molecules SREBP-1 and PGC1-α. The negative effect of AFP on mitochondrial metabolism and ATP production was confirmed with observation of reduction in basal oxygen consumption rate (OCR) in DCs exposed to AFP derived from cord blood. More severe reduction in basal OCR was observed in tumor-derived DCs exposed to AFP due to downregulation of cytochrome c oxidase. We also showed reduced expression of PGC1-α in circulating myeloid DCs of patients with HCC and impaired capacity to stimulate antigen-specific effector functions. These data show the negative effects of AFP on DC metabolism. These findings elucidate a mechanism of immune suppression in HCC and may help generate therapeutic approaches to reverse such immunosuppression.