bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrologic and thermal conditions occupied by a species within a single watershed predict the geographic extent of occurrence of freshwater fishes
Authors: VanCompernolle Michelle , Knouft Jason H. , Ficklin Darren L.
Published: January 2019

Hydrologic regimes and water temperatures are primary predictors of freshwater species occurrence. Although these variables have been demonstrated to be important in regulating species diversity at particular locations, whether species occurrences across lotic habitats within a single, relatively small watershed can predict the full geographic extent of a species is unclear. We use river reach estimates of streamflow and water temperature derived from a watershed‐scale hydrologic model, coupled with body size measures, to investigate whether the type and variability of thermal and hydrologic habitat used by fish species within the Mobile River Basin (MRB) can predict the overall geographic extent of occurrence (GEO) for these taxa. Locality data for 108 species of fishes within MRB, one of the most ecologically diverse watersheds in the United States, were intersected with streamflow and water temperature estimates to characterize minimum and maximum streamflow and water temperature conditions and thermal breadth (range of thermal conditions) occupied by each species. Among all species, variation in GEO was associated with variation in thermal breadth and body size. Thermal variables were also important predictors of variation in GEO among Cyprinidae. Flow variables were important predictors of variation in GEO for Centrarchidae, Ictaluridae, and Percidae and within Etheostoma and Percina. Results generally indicate that species with large body size, relatively broad thermal tolerances, or preference for relatively high discharge environments tend to exhibit broader distributions across North America, yet these relationships vary among taxonomic groups.
Peptide nucleic acid and amino acid modified peptide nucleic acid analysis by capillary zone electrophoresis
Authors: Wang Xiaoqian , Li Linsen , Khan Rizwan Ullah , Qu Feng
Published: January 2019

A rapid, high resolution, and low sample consumption CZE method is developed for peptide nucleic acid (PNA) analysis for the first time. 30% v/v acetonitrile in PNA sample and 20% v/v acetonitrile in 50 mM borax‐boric acid (pH 8.7) as BGE were employed after optimization. The calibration curves were linear for PNA concentration ranging from 1 to 50 μmol/L. LOD and LOQ of PNA were 0.2 and 1.0 μmol/L, respectively. Since the commercially available reagent gives rise to huge PNA peak and an apparent impurity peak, the purity of PNA was evaluated to be about 81.4% by CZE method, obviously lower than the supplier's purity value of 99.9% evaluated by RP–HPLC, and also lower than 94.8% determined with RP–HPLC by our research group. The CZE method takes only 5 min, needs only 90 nL PNA, much less than 20 min and 20 μL PNA in RP–HPLC method. Moreover, the CZE method is applicable for the analysis of glutamic acid modified and lysine modified PNAs, they show different migration time with their corresponding complementary PNAs. Our results show CZE provides a new choice for PNA and modified PNA analysis, also their purity or quality evaluation.
DNA polymerase kappa counteracts inflammation‐induced mutagenesis in multiple organs of mice
Authors: Hakura Atsushi , Sui Hajime , Sonoda Jiro , Matsuda Tomonari , Nohmi Takehiko
Published: January 2019

In vitro studies indicate that DNA polymerase kappa (Polκ) is able to accurately and efficiently perform DNA synthesis using templates containing various types of DNA damage, including benzo[a]pyrene (BP)‐induced N2‐deoxyguanosine adducts. In this study, we examined sensitivity of inactivated Polk knock‐in (Polk−/−) mice to BP carcinogenicity in the colon by administering an oral dose of BP plus dextran sulfate sodium (DSS), an inflammation causing promoter of carcinogenesis. Although colon cancer was successfully induced by BP plus DSS, there was no significant difference in tumor incidence or multiplicity between Polk−/− and Polk+/+ mice. Malignant lymphoma was induced in thymus by the treatment only in Polk−/− mice, but it lacked statistical significance. Mutant frequencies (MFs) in the gpt reporter gene were strongly enhanced in colon; almost to the same extent in both types of mice. Micronucleus formation in bone marrow at the high dose of BP and DNA adducts in colon and lung was not significantly different between two types of mice. Surprisingly, however, Polk−/− mice exhibited significantly higher MFs in colon and lung than did Polk+/+ mice when they were treated with DSS alone. The most prominent mutation induced by DSS treatment was G:C to C:G transversion, whose specific MF in proximal colon was 30 times higher in Polk−/− than in Polk+/+ mice. DSS alone did not enhance MF at all in Polk+/+ mice. The results indicate that Polκ does not suppress BP‐induced mutagenesis and carcinogenesis in the colon, but counteracts inflammation‐induced mutagenesis in multiple organs. Environ. Mol. Mutagen. 60:320–330, 2019. © 2019 Wiley Periodicals, Inc.
Multiyear monitoring of bird communities in chlorpyrifos-treated orchards in Spain and the United Kingdom: Spatial and temporal trends in species composition, abundance, and site fidelity
Authors: Dittrich Ralf , Giessing Benedikt , Benito María M. , Russ Anja , Wolf Christian , Foudoulakis Manousos , Norman Steve
Published: January 2019

The relationship between agricultural practices and the welfare of wild birds has gained increased attention over the last decades. To assess the potential effects of chlorpyrifos on the bird community, a multiyear, multisite monitoring program was carried out in treated cider orchards (in the United Kingdom) and treated citrus orchards (in Spain). Constant-effort mist netting was used over several consecutive years in the United Kingdom (2012–2014) and Spain (2010–2012). The general structure of the bird community and the presence of breeding species were analyzed. Twelve and 11 bird species (out of 81 and 45 trapped) in Spain and the United Kingdom, respectively, exceeded the 2% dominance value. For a selection of 6 species in citrus and 4 in cider orchards, N-mixture models were fitted to the number of trapped birds. The abundance of most species was strongly and significantly affected by seasonality. No species showed any indication of reduction in population size over the years. The results of this extensive field program support the indications that chlorpyrifos spray applications present a low risk to the bird community over the years. Environ Toxicol Chem 2019;38:616–629. © 2018 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on behalf of SETAC.
Exact variance component tests for longitudinal microbiome studies
Authors: Zhai Jing , Knox Kenneth , Twigg Homer L. , Zhou Hua , Zhou Jin J.
Published: January 2019

In metagenomic studies, testing the association between microbiome composition and clinical outcomes translates to testing the nullity of variance components. Motivated by a lung human immunodeficiency virus (HIV) microbiome project, we study longitudinal microbiome data by using variance component models with more than two variance components. Current testing strategies only apply to models with exactly two variance components and when sample sizes are large. Therefore, they are not applicable to longitudinal microbiome studies. In this paper, we propose exact tests (score test, likelihood ratio test, and restricted likelihood ratio test) to (a) test the association of the overall microbiome composition in a longitudinal design and (b) detect the association of one specific microbiome cluster while adjusting for the effects from related clusters. Our approach combines the exact tests for null hypothesis with a single variance component with a strategy of reducing multiple variance components to a single one. Simulation studies demonstrate that our method has a correct type I error rate and superior power compared to existing methods at small sample sizes and weak signals. Finally, we apply our method to a longitudinal pulmonary microbiome study of HIV‐infected patients and reveal two interesting genera Prevotella and
Veillonella associated with forced vital capacity. Our findings shed light on the impact of the lung microbiome on HIV complexities. The method is implemented in the open‐source, high‐performance computing language
Julia and is freely available at https://github.com/JingZhai63/VCmicrobiome.
Late Quaternary deformation in parts of the Belt of Schuppen of Dimapur and Peren districts, Nagaland, NE India
Authors: Moiya Jaowang N. , Luirei Khayingshing , Longkumer Limasanen , Kothyari Girish Ch. , Thong Glenn T.
Published: January 2019

Geomorphic evidences and geochronology suggest recent tectonic activity in the Belt of Schuppen of Dimapur and Peren districts of Nagaland. Multiple levels of strath terraces forming remarkable geomorphic expressions are observed along the Chathe and Jharnapani river valleys. They indicate episodic uplift of the hanging‐wall blocks of the thrust systems. The major lineaments prominently trend parallel to the NE–SW regional thrusts, some being perpendicular or oblique. Active normal faults displacing bedrock and overlying fill sediments point to recent tectonic activity. The parallel and trellis drainage patterns are lineament‐controlled. Uplift of the terrain is evident from successive palaeochannels of the Chathe River younging towards the southwest. Three major aggradational phases of the terrace sediments are inferred from optically stimulated luminescence (OSL) chronology, the oldest beginning around 21 ka, the second around 11–7 ka, and the youngest between 3.5 and 1 ka. A sand lens of a tilted strath terrace exposed between Kukidolong and Chumukedima is dated at 7 ka, indicating tectonic events after 7 ka. Five major phases of bedrock uplift/incision have been estimated during 20 ka (0.13 mm/year), 11 ka (0.92 mm/year), 9 ka (2.29 mm/year), 6 ka (0.67 mm/year), and 1.8 ka (2.6 mm/year). Transverse topographic symmetry and asymmetry factor data suggest tilting towards the NE and SW. Other morphometric indices, such as channel sinuosity, stream length gradient index, valley floor to valley height ratio, and mountain front sinuosity, suggest that the area is tectonically active, which corroborates field observations.
A novel myelin protein zero transgenic zebrafish designed for rapid readout of in vivo myelination
Authors: Preston Marnie A. , Finseth Lisbet T. , Bourne Jennifer N. , Macklin Wendy B.
Published: January 2019

Demyelination occurs following many neurological insults, most notably in multiple sclerosis (MS). Therapeutics that promote remyelination could slow the neurological decline associated with chronic demyelination; however, in vivo testing of candidate small molecule drugs and signaling cascades known to impact myelination is expensive and labor intensive. Here, we describe the development of a novel zebrafish line which uses the putative promoter of Myelin Protein Zero (mpz), a major structural protein in myelin, to drive expression of Enhanced Green Fluorescent Protein (mEGFP) specifically in the processes and nascent internodes of myelinating glia. We observe that changes in fluorescence intensity in Tg(mpz:mEGFP) larvae are a reliable surrogate for changes in myelin membrane production per se in live larvae following bath application of drugs. These changes in fluorescence are strongly predictive of changes in myelin‐specific mRNAs [mpz, 36K and myelin basic protein (mbp)] and protein production (Mbp). Finally, we observe that certain drugs alter nascent internode number and length, impacting the overall amount of myelin membrane synthesized and a number of axons myelinated without significantly changing the number of myelinating oligodendrocytes. These studies demonstrate that the Tg(mpz:mEGFP) reporter line responds effectively to positive and negative small molecule regulators of myelination, and could be useful for identifying candidate drugs that specifically target myelin membrane production in vivo. Combined with high throughput cell‐based screening of large chemical libraries and automated imaging systems, this transgenic line is useful for rapid large scale whole animal screening to identify novel myelinating small molecule compounds in vivo.
Does state ownership hurt or help minority shareholders? International evidence from control block acquisitions
Authors: Heugens Pursey P. M. A. R. , Sauerwald Steve , Turturea Roxana , van Essen Marc
Published: January 2019

Research Summary

We argue that state ownership is a crucial policy instrument for alleviating what is perhaps the most important principal–principal (PP) agency problem around the globe: private benefits of control (PBC). Our results illustrate that states reduce PBC in the companies in which they acquire controlling ownership positions. We also examine how legal and political institutions influence the extent to which states accomplish this goal. Antiself‐dealing legal regulations make states more effective in their efforts to constrain PBC, while political constraints make them less effective. Regimes with high state capacity appear not to prioritize PBC reduction. We test and corroborate these ideas in a sample of 1,354 control transactions across 54 countries.

Managerial Summary

The one‐sided appropriation of wealth by dominant owners is arguably the biggest threat to minority shareholders around the globe. An important question that has thus far remained unaddressed is whether state ownership of firms increases or decreases the extraction of these so‐called PBC. By investigating a large number of transactions involving the transfer of corporate control in 54 countries, we find that state acquirers of controlling ownership positions generally respect minority shareholder rights more than other types of new controlling shareholders. This effect is stronger in countries with strong legal protection of minority shareholders. However, political constraints make it more challenging for state acquirers to keep PBC in check while “strong” states may (mis)use the firms they invest in as policy vehicles.
IMRT‐based treatment of unknown primary malignancy of the head and neck: Outcomes and improved toxicity with decreased mucosal dose and larynx sparing
Authors: LaVigne Anna W. , Margalit Danielle N. , Rawal Bhupendra , Puzanov Maria , Annino Donald J. , Goguen Laura A. , Sher David J. , Schoenfeld Jonathan D. , Chau Nicole G. , Lorch Jochen H. , Rabinowits Guilherme , Haddad Robert I. , Tishler Roy B.
Published: January 2019

Background

Radiation therapy for squamous cell cancer of the head and neck with unknown primary (head and neck CUP) has been associated with significant levels of swallowing toxicity. We examined the effect of changes in mucosal dose on development of laryngeal strictures and percutaneous endoscopic gastrostomy (PEG) dependence.

Methods

Retrospective analysis of 58 patients with head and neck CUP treated with intensity‐modulated radiation therapy (IMRT) at the Dana Farber Cancer Institute from August 2004 through July 2013.

Results

There were no significant differences between any recurrences for groups treated to 56 versus ≥60 Gy to the mucosal surfaces. However, mucosal dose and chemotherapy type were associated with stricture on multivariable analysis; median PEG dependence was decreased for patients treated to 56 Gy. A larynx‐sparing approach was associated with improved outcomes for strictures and PEG use.

Conclusion

In this single institution study, a 56 Gy IMRT‐based mucosal dose demonstrated significant improvements in swallowing toxicity. Additional benefit was seen with larynx‐sparing IMRT.
Impact of retropharyngeal lymph node dissection in the surgical treatment of hypopharyngeal cancer
Authors: Teshima Masanori , Otsuki Naoki , Shinomiya Hirotaka , Morita Naruhiko , Furukawa Tatsuya , Morimoto Koichi , Nakamura Tetsu , Hashikawa Kazunobu , Kiyota Naomi , Sasaki Ryohei , Nibu Ken‐ichi
Published: January 2019

Objectives

To evaluate the impact of retropharyngeal lymph node (RPLN) dissection in the surgical treatment of hypopharyngeal cancer.

Methods

Between 2007 and 2016, 98 previously untreated patients with pathological diagnosed hypopharyngeal squamous cell carcinoma underwent total pharyngolaryngectomy and bilateral neck dissection at Kobe University Hospital. Bilateral dissection of RPLN was simultaneously performed in all patients. Pharynx was reconstructed with free jejunal transfer in 94 patients and primarily closed in 4 patients. Postoperative chemoradiotherapy was performed in patients with high risk factors including metastasis to RPLN, multiple lymph node metastasis, extranodal invasion, and/or positive/close surgical margins.

Results

The median follow‐up period was 25 months ranging from 1 to 105 months. RPLN adenopathy was preoperatively identified in 9 patients in FDG‐positron emission tomography. All of them had pathologically diagnosed RPLN metastases, which had been controlled in all patients during the observation periods. Among the other 89 patients, 7 patients had RPLN metastasis. The 2‐year overall survival rates of the patients with and without RPLN metastasis were 65.7% and 69.8% (P = .61), respectively.

Conclusions

In the present study, patients with RPLN metastasis showed equally favorable oncological outcome compared with patients without RPLN metastasis. At least, ipsilateral RPLN dissection should be considered in the surgical treatment of advanced hypopharyngeal cancer and multiple neck lymph node metastasis regardless of primary subsite.
Impact of lymph node sampling on survival in cN0 major salivary gland adenoid cystic carcinoma
Authors: Qian Zhen Jason , Chen Michelle M. , Divi Vasu , Megwalu Uchechukwu C.
Published: January 2019

Background

The role of elective neck dissection in the management of major salivary gland adenoid cystic carcinoma is unclear.

Methods

Data were retrospectively extracted from the National Cancer Center Database. The study cohort included 1504 patients with adenoid cystic carcinoma of major salivary glands with clinical N0 necks who were treated with surgery between 2004 and 2014. The cohort was divided into four groups based on number of lymph nodes (LNs) examined on pathology: 0, 1‐8, 9‐17, and ≥18 LNs.

Results

The rate of occult nodal metastasis was 9.0%. Number of LNs removed was not associated with survival (Reference, 0 LNs; HR = 0.98, 95% CI 0.73‐1.32 for 1‐8 LNs; HR = 1.22, 95% CI 0.80‐1.88 for 9‐17 LNs; HR = 0.94, 95% CI 0.61‐1.46 for ≥18 LNs) after adjusting for important covariates.

Conclusions

LN sampling is not associated with survival in cN0 major salivary gland ACC.
Prognostic significance of tumor budding, tumor‐stroma ratio, cell nests size, and stroma type in laryngeal and pharyngeal squamous cell carcinomas
Authors: Karpathiou Georgia , Vieville Marine , Gavid Marie , Camy Florian , Dumollard Jean Marc , Magné Nicolas , Froudarakis Marios , Prades Jean Michel , Peoc'h Michel
Published: January 2019

Background

Despite immune microenvironment of head and neck squamous cell carcinoma (HNSCC) has been studied, there are no sufficient data on the role of tumor stroma factors. The aim of the study was to explore the prognostic and predictive role of these factors in a large series of HNSCC.

Methods

This is a retrospective study of 266 patients with laryngeal and pharyngeal SCC. Clinical data were correlated with the following histological parameters: tumor‐stroma ratio (TSR), tumor budding activity (BA), cell nests size (CNS), and stroma type.

Results

Stroma‐rich tumors, tumor budding, smaller CNS at core and front area, and fibroblastic stroma type, were all adverse prognostic factors (P < 0.0001, 0.001, 0.003, 0.001, 0.007, respectively). Stroma‐poor tumors and with larger CNS showed good response to induction chemotherapy (P = 0.009 and 0.02, respectively).

Conclusions

TSR, tumor budding, CNS, and stroma type are important prognostic and predictive factors in laryngeal and pharyngeal SCC.
Adjuvant external beam radiotherapy for locally invasive papillary thyroid cancer
Authors: Megwalu Uchechukwu C. , Orloff Lisa A. , Ma Yifei
Published: January 2019

Background

The goal of this study was to assess the impact of adjuvant external beam radiotherapy (EBRT) on survival in patients with locally invasive papillary thyroid carcinoma.

Methods

Propensity score analysis was performed on 870 patients with surgically resected T4 papillary thyroid carcinoma, identified in the Surveillance, Epidemiology, and End Results Database between 1988 and 2013.

Results

EBRT was associated with worse overall survival (OS) (HR 1.60, 95% CI 1.18‐2.16) and disease‐specific survival (DSS) (HR 1.58, 1.09‐2.30). Subset analysis of patients with major extrathyroidal invasion showed that EBRT was associated with worse OS (HR 1.53, 95% CI 1.04‐2.25), but not with DSS (HR 1.57, 95% CI 0.99‐2.50).

Conclusion

Adjuvant EBRT, in the initial management of locally invasive papillary thyroid cancer, was not associated with a survival benefit. Future studies are needed to determine which subset of patients may benefit from adjuvant EBRT.
Noninvasive Evaluation of Liver Fibrosis and Portal Hypertension After Successful Portoenterostomy for Biliary Atresia
Authors: Hukkinen Maria , Lohi Jouko , Heikkilä Päivi , Kivisaari Reetta , Jahnukainen Timo , Jalanko Hannu , Pakarinen Mikko P.
Published: January 2019

We investigated noninvasive follow‐up markers for histologic liver fibrosis and portal hypertension (PH) in patients with biliary atresia after successful portoenterostomy (PE). Among children with bilirubin <20 µmol/L after PE (n = 39), Metavir fibrosis stage was evaluated at PE and in follow‐up protocol liver biopsies (n = 83). PH was defined as endoscopically confirmed esophageal varices or thrombocytopenia associated with splenomegaly. The accuracy of liver biochemistry and stiffness in detecting liver fibrosis and PH was analyzed by the area under the receiving operating characteristic curve (AUROC) and multiple regression models. During a median native liver survival of 8.3 years (interquartile range 2.5‐10.8 years), cirrhosis (Metavir F4) had developed in 51% of patients and PH in 54% of patients. Cirrhosis was equally common in all age tertiles of 1.2‐2.1 years (n = 10/27), 3.9‐5.8 years (n = 12/28), and 9.0‐14 years (n = 12/28). In the two oldest age tertiles, histologic liver fibrosis had progressed further in patients with PH than without PH (P < 0.001). PH was accurately predicted by the aspartate aminotransferase‐to‐platelet ratio index (APRI) (cutoff, 0.70; AUROC, 0.92), bile acids (cutoff, 49 µmol/L; AUROC, 0.91), and liver stiffness (cutoff, 16.9 kPa; AUROC, 0.89; P < 0.001 each) across all age tertiles. Liver stiffness was the most accurate predictor of cirrhosis overall (AUROC, 0.82; P < 0.001), whereas bilirubin was >11 µmol/L in the youngest tertile (AUROC, 0.91; P < 0.001), bile acids was >80 µmol/L in the middle tertile (AUROC, 0.81; P = 0.009), and liver stiffness was >24 kPa in the oldest age tertile (AUROC, 0.96; P = 0.002). Conclusion: After successful PE, development of PH associates with progression of liver fibrosis and can be accurately detected by APRI and stiffness. Liver stiffness most accurately identified cirrhosis in older children, whereas biochemical markers of cholestasis closely reflected histologic cirrhosis in younger children.
Using Decision Analysis to Provide Integrated, Transparent Trade‐off Analysis
Authors: Specking Eric
Published: January 2019

Clients often ask systems engineers to communicate the complexities of their studies or to review/understand someone else's study. Exploring, evaluating, and communicating the tradespace is difficult to do, especially when reviewing others’ work, due to the lack of knowledge of the tradespace, number and types of models, the complexities of the analysis, and the adequacy of the documentation. Additionally, it is challenging to identify and demonstrate important trade‐offs found throughout the design decision process. This demonstrates a need to understand the complexities of the analysis, be able to visualize their relationships, and then be able to communicate it to others in a simplified manner that technical and non‐technical stakeholders can understand. This article describes: (1) how system engineering requires descriptive, predictive, and prescriptive analytics in early system design, (2) a framework for an integrated trade‐off analytics approach that incorporates the various analytics categories with model‐based engineering and model‐based system engineering, and (3) a decision analysis tool called the trade‐off analytics hierarchy that transparently identifies and communicates the complexities of an analysis to stakeholders.
LINC00461 promotes cell migration and invasion in breast cancer through miR‐30a‐5p/integrin β3 axis
Authors: Dong Lifeng , Qian Junbin , Chen Fangfang , Fan Yangfan , Long Jingpei
Published: January 2019

Mounting evidence has demonstrated that long noncoding RNAs (lncRNAs) are dysregulated and implicated in the occurrence and development of a wide range of human malignancies. LINC00461, a novel cancer‐related lncRNA, has been reported to be highly expressed and serve as oncogene in glioma; however, its biological role in breast cancer (BC) remains obscure. This study aimed to explore the role of LINC00461 in BC and elucidate the potential molecular mechanisms involved. In the current study, LINC00461 was found to be significantly upregulated in both BC tissues and cell lines. Besides, we found that high LINC00461 expression was associated with TNM stage and differentiation. Furthermore, functional studies demonstrated that LINC00461 expedited BC cell migration and invasion. Notably, LINC00461 was observed to enhance the expression of vimentin and zinc‐finger E‐box binding homeobox factor 1, suppress the expression of E‐cadherin, and promote the activation of extracellular signal‐regulated kinase and AKT signaling pathways. Mechanical investigations revealed that LINC00461 positively modulated integrin β3 (ITGB3) expression as miR‐30a‐5p sponge in BC cells. Taken together, LINC00461 exerts an oncogenic role in BC through miR‐30a‐5p/ITGB3 axis. Our data indicate that LINC00461 may be used to be a novel candidate therapeutic target and a valuable diagnostic biomarker for BC.
Celastrol protects human retinal pigment epithelial cells against hydrogen peroxide mediated oxidative stress, autophagy, and apoptosis through sirtuin 3 signal pathway
Authors: Du Zhaojiang , Zhang Wen , Wang Shengyu , Zhang Jing , He Jingang , Wang Yuan , Dong Yuhong , Huo Min
Published: January 2019

Age‐related macular degeneration (AMD), one of the most common causes of visual impairment, often occurrs in the elderly in developed countries. Oxidative stress, autophagy, and apoptosis of retinal pigment epithelial (RPE) cells play roles in the pathogenesis of AMD. In the current study, the protective effect of celastrol against hydrogen peroxide (H2O2)‐induced oxidative stress and apoptosis was investigated using a human RPE cell line (ARPE‐19). H2O2 inhibited ARPE‐19 cells' survival and autophagy and induced their oxidative stress and apoptosis. Compared with the H2O2 group, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay showed that celastrol increased ARPE‐19 cells' survival in a dose‐ and time‐dependent manner. Further, studies have suggested that celastrol has antioxidative stress and antiapoptosis effects in H2O2‐treated ARPE‐19 cells. Also, cell autophagy is activated by celastrol in H2O2‐treated ARPE‐19 cells. Reverse transcription polymerase chain reaction and Western blot showed that celastrol elevated the messenger RNA (mRNA) and protein expression of sirtuin 3 (SIRT3) in H2O2‐induced ARPE‐19 cells. Inhibition of the level of SIRT3 by SIRT3 small interfering RNA (siRNA) reversed the effects of celastrol on oxidative stress, autophagy, and apoptosis in H2O2‐induced ARPE‐19 cells. In conclusion, these observations suggest that celastrol activates the SIRT3 pathway in RPE cells and protects against H2O2‐induced oxidative stress and apoptosis.
TCEA3 promotes differentiation of C2C12 cells via an Annexin A1‐mediated transforming growth factor‐β signaling pathway
Authors: Ge Yao , Li Shuang , Hu Xiao‐Yang , Tong Hui‐Li , Li Shu‐Feng , Yan Yun‐Qin
Published: January 2019

TCEA3 is a member of the transcription elongation factor family that not only promotes transcription but may also participate in other cytoplasmic processes. However, its mechanisms of action remain unclear. Our previous study indicated that TCEA3 may affect muscle differentiation. In this study, we investigated the expression and localization of TCEA3 in C2C12 cells and examined the role of TCEA3 in differentiation, its interaction with other cell proteins, and mechanisms of action. We found that the expression of TCEA3 increased gradually with an increase in the number of differentiation days and that it is mainly expressed in the cytoplasm of C2C12 cells, of which it promotes differentiation. Coimmunoprecipitation experiments and western blot analysis revealed that TCEA3 interacts with Annexin A1 (ANXA1), which is located in the cytoplasm and also promotes cell differentiation. Collectively, our results indicate that TCEA3 promotes cell differentiation by interacting with ANXA1 and affecting transforming growth factor‐β signaling pathways.
Circulating cell‐free DNA release in vitro: kinetics, size profiling, and cancer‐related gene methylation
Authors: Panagopoulou Maria , Karaglani Makrina , Balgkouranidou Ioanna , Pantazi Chrisoula , Kolios George , Kakolyris Stylianos , Chatzaki Ekaterini
Published: January 2019

Circulating cell‐free DNA (ccfDNA) is a biological entity of great interest due to its potential as liquid biopsy biomaterial carrying clinically valuable information. To better understand its nature, we studied ccfDNA in vitro in two human cancer cell lines MCF‐7 and HeLa. Normalized indexes of ccfDNA per cell population decreased over time of culture but were significantly elevated after exposure to IC50 doses of the demethylating/apoptotic agent 5‐azacytidine (5‐AZA‐CR). Fragment‐size profiling was indicative of active release, whereas exposure to 5‐AZA‐CR induced the release of additional shorter fragments, indicative of apoptosis. Finally, the methylation profile of a panel of cancer‐specific genes as assessed by quantitative methylation analysis in ccfDNA was identical to the corresponding genomic DNA and followed accurately changes caused by 5‐AZA‐CR. Overall, our in vitro findings support that ccfDNA can be a reliable biosource of clinically relevant information that can be further studied in these cell culture models.
The role of adipose TRP channels in the pathogenesis of obesity
Authors: Gao Peng , Yan Zhencheng , Zhu Zhiming
Published: January 2019

The prevalence of obesity is continuously increasing worldwide. Transient receptor potential (TRP) channels constitute a family of nonselective cation channels that are ubiquitously expressed in mammalian tissues, including adipose tissue. Although TRP channels might be regarded as therapeutic targets for obesity due to the inhibitory effects of their agonists on body weight and adiposity, the exact role of TRP channels in the development of obesity by modulating the function of adipose tissue has not been systemically reviewed. Multiple TRP channels are present in adipocytes and are involved in diverse aspects of cellular function, including differentiation and maturation of white adipose tissue (WAT), browning of WAT and thermogenesis of brown adipose tissue (BAT). Most of these functions are mediated by alterations in intracellular Ca2+ levels or subcellular Ca2+ signaling pathway. TRP channels influence intracellular Ca2+ dynamics through directly mediating Ca2+ entry (TRPVs and others) or store‐operated mechanisms (TRPCs). Intracellular Ca2+ displays a biphasic effect on regulation adipocyte behaviors depending on the differentiation stage, which may account for the different roles of individual TRP channels in regulation of adiposity. This review emphasizes the contribution of TRP channels to obesity and provide an in‐depth discussion on the complexity of their mechanism of actions.
The role of physical forces in osteoclastogenesis
Authors: Ma Qinyu , Ma Zaisong , Liang Mengmeng , Luo Fei , Xu Jianzhong , Dou Ce , Dong Shiwu
Published: January 2019

The movements of life at every level from organs, tissues, cells to sub‐cells, are all conducted in certain physical environments. In the human body, skeletal tissue among all connective tissues is influenced the most by physical forces. Studying the biological behavior of bone cells under different physical environments is helpful in further understanding bone homeostasis and metabolism. Among all bone cells, osteoclast (OC) and OC steered bone remodeling is one of the key points in bone metabolism. In the past few decades, people's understanding of OC was mostly limited to its involvement of bone resorption under physiological and pathological conditions. However, more and more studies started to focus on how physical forces affect the formation and differentiation of OC. This review tries to illustrate the knowledge up to date about how osteoclastogenesis is regulated by physical forces through direct and indirect ways, including fluid shear force, compressive force, and microgravity. The direct way describes the straightforward effects produced by different forces in osteoclastogenesis, whereas the indirect way describes the effects of different forces in osteoclastogenesis through regulation of other bone cells when a certain force is applied. Molecular mechanisms were analyzed and reviewed in both direct and indirect regulation by different forces. Finally, we discussed the status quo and tendency of related research, as well as other unresolved issues, and some future prospects.
Mechanisms of apoptosis modulation by curcumin: Implications for cancer therapy
Authors: Mortezaee Keywan , Salehi Ensieh , Mirtavoos‐mahyari Hanifeh , Motevaseli Elahe , Najafi Masoud , Farhood Bagher , Rosengren Rhonda J. , Sahebkar Amirhossein
Published: January 2019

Cancer incidences are growing and cause millions of deaths worldwide. Cancer therapy is one of the most important challenges in medicine. Improving therapeutic outcomes from cancer therapy is necessary for increasing patients’ survival and quality of life. Adjuvant therapy using various types of antibodies or immunomodulatory agents has suggested modulating tumor response. Resistance to apoptosis is the main reason for radioresistance and chemoresistance of most of the cancers, and also one of the pivotal targets for improving cancer therapy is the modulation of apoptosis signaling pathways. Apoptosis can be induced by intrinsic or extrinsic pathways via stimulation of several targets, such as membrane receptors of tumor necrosis factor‐α and transforming growth factor‐β, and also mitochondria. Curcumin is a naturally derived agent that induces apoptosis in a variety of different tumor cell lines. Curcumin also activates redox reactions within cells inducing reactive oxygen species (ROS) production that leads to the upregulation of apoptosis receptors on the tumor cell membrane. Curcumin can also upregulate the expression and activity of p53 that inhibits tumor cell proliferation and increases apoptosis. Furthermore, curcumin has a potent inhibitory effect on the activity of NF‐κB and COX‐2, which are involved in the overexpression of antiapoptosis genes such as Bcl‐2. It can also attenuate the regulation of antiapoptosis PI3K signaling and increase the expression of MAPKs to induce endogenous production of ROS. In this paper, we aimed to review the molecular mechanisms of curcumin‐induced apoptosis in cancer cells. This action of curcumin could be applicable for use as an adjuvant in combination with other modalities of cancer therapy including radiotherapy and chemotherapy.
Cover Image, Volume 94, Issue 2
Authors: Anane Emmanuel , Sawatzki Annina , Neubauer Peter , Cruz‐Bournazou Mariano Nicolas
Published: January 2019

The cover image is based on the Research Article Modelling concentration gradients in fed‐batch cultivations of E. coli ‐ towards the flexible design of scale‐down experiments by Emmanuel Anane et al., DOI: 10.1002/jctb.5798.

image
Monitoring of long‐term parenteral nutrition in children with intestinal failure
Authors: Zemrani Boutaina , Bines Julie E
Published: January 2019

Pediatric intestinal failure (IF) is a rare and complex condition associated with significant morbidity and mortality. It is defined as the reduction of gut mass or function below the minimal needed for absorption of nutrients and fluid to sustain life and growth. Since the advent of specialized multidisciplinary intestinal rehabilitation centers, IF management has considerably evolved in the last years, but serious complications of long‐term parenteral nutrition (PN) can occur. Main complications include intestinal failure‐associated liver disease, growth failure, body composition imbalance, central venous access complications, micronutrient deficiencies and toxicities, metabolic bone disease, small intestinal bacterial overgrowth, and renal disease. With improvement in survival rates of patients over the last 20 years, emphasis should be on limiting IF‐related comorbidities and improving quality of life. Close monitoring is pivotal to ensuring quality of care of these patients. The care of children with chronic IF should involve a comprehensive monitoring plan with flexibility for individualization according to specific patient needs. Monitoring of children on long‐term PN varies significantly across units and is mainly based on experience, although few guidelines exist. This narrative review summarizes the current knowledge and practices related to monitoring of children with IF. The authors also share their 20‐year experience at the Royal Children's Hospital in Melbourne Australia on this topic.
Online Ramsey theory for a triangle on ‐free graphs
Authors: Choi Hojin , Choi Ilkyoo , Jeong Jisu , Oum Sang‐il
Published: January 2019

Given a class of graphs and a fixed graph , the online Ramsey game for H on is a game between two players Builder and Painter as follows: an unbounded set of vertices is given as an initial state, and on each turn Builder introduces a new edge with the constraint that the resulting graph must be in , and Painter colors the new edge either red or blue. Builder wins the game if Painter is forced to make a monochromatic copy of at some point in the game. Otherwise, Painter can avoid creating a monochromatic copy of forever, and we say Painter wins the game. We initiate the study of characterizing the graphs such that for a given graph , Painter wins the online Ramsey game for on ‐free graphs. We characterize all graphs such that Painter wins the online Ramsey game for on the class of ‐free graphs, except when is one particular graph. We also show that Painter wins the online Ramsey game for on the class of ‐minor‐free graphs, extending a result by Grytczuk, Hałuszczak, and Kierstead [Electron. J. Combin. 11 (2004), p. 60].
Memantine can relieve the neuronal impairment caused by neurotropic virus infection
Authors: Sun Leqiang , Zhou Meiling , Liu Chuangang , Tang Yajie , Xiao Ke , Dai Jinxia , Gao Zhisong , Siew Leonard , Cao Gang , Wu Xiang , Li Liang , Zhang Ran
Published: January 2019

Neurotropic viruses, such as the rabies virus (RABV) and Japanese encephalitis virus (JEV), induce neuronal dysfunction and complication, causing neuronal damage. Currently, there are still no effective clinical treatments for neuronal injury caused by neurotropic viruses. Memantine, a drug capable of passing through the blood‐brain barrier, noncompetitively and reversibly binds to n‐methyl‐
d‐aspartic acid (NMDA) receptors. Memantine is used to treat Alzheimer's disease by blocking the activation of extra axonal ion channels, thus preventing neuronal degeneration by inhibiting the abnormal cytosolic Ca
2+ increase. To explore whether memantine can alleviate neurological disturbances caused by RABV and JEV, the following experiments were carried out: (1) for primary neurons cultured in vitro infected with RABV, the addition of memantine showed neuroprotection. (2) In the RABV challenge experiments, memantine had limited therapeutic effect, mildly extending the survival time of mice. In contrast, memantine significantly prolonged the survival time of mice infected with JEV, by reducing the intravascular cuff and inflammatory cell infiltration in mice. Furthermore, memantine decreases the amount of JEV virus in mice brain.
Can pride be a vice and virtue at work? Associations between authentic and hubristic pride and leadership behaviors
Authors: Yeung Edward , Shen Winny
Published: January 2019

Pride, a discrete emotion that drives the pursuits of achievement and status, is crucial to consider in leadership contexts. Across three studies, we explored how leaders' experiences of authentic and hubristic pride were associated with their leadership behaviors. In Study 1, a field study of leader–follower dyads, leader trait authentic pride was associated with the use of more effective (i.e., consideration and initiating structure) and fewer ineffective (i.e., abusive supervision) leadership behaviors, and hubristic pride was associated with more abusive behaviors. In Study 2, a daily diary study, on days when leaders experienced more authentic pride than usual, they used more effective leadership behaviors than usual, whereas on days when leaders experienced more hubristic pride than typical, they were more likely to engage in abusive supervision than typical. In Study 3, a scenario‐based experiment, leaders who experienced more authentic pride in response to our experimental manipulation were more likely to intend to use effective leadership behaviors. In contrast, those who experienced more hubristic pride were less likely to use these behaviors and more likely to intend to be abusive. Overall, this work highlights the importance of pride for leadership processes and the utility of examining discrete and self‐conscious emotions within organizations.
Revisiting interannual to decadal teleconnections influencing seasonal rainfall in the Greater Horn of Africa during the 20th century
Authors: Bahaga Titike K. , Fink Andreas H. , Knippertz Peter
Published: January 2019

This paper revisits teleconnections for three major rainy seasons at the Greater Horn of Africa for the period 1901–2013. Sea surface temperature‐based climate indices known to influence Short, Kiremt, and Long Rains are used in a comprehensive statistical analysis to detect non‐stationary behaviour in teleconnections and to split them into interannual and decadal time scales. Physical mechanisms are proposed for identified significant non‐stationary teleconnections. Interannual variability in the October–December Short Rains is predominantly influenced by the Indian Ocean Dipole (IOD) with a percent variance explained (PVE) of up to 80% in recent years. However, abrupt shifts in this teleconnection occurred around 1918, 1951, 1987, and recently. The Short Rains also correlate strongly with El Niño‐Southern Oscillation (ENSO). However, ENSO influence on Short Rains is mediated by in‐phase occurrence of IOD. Decadal variations in Short Rains are more directly explained by low‐frequency variability in the Pacific Ocean (PO). A hitherto undocumented non‐stationary relation was found between Atlantic Niño 3 and June–September Kiremt Rains. The non‐stationarity seems to be related to a decadal regime shift in the West African monsoon system in the late 1960s. The variability of Kiremt Rains is also strongly associated with ENSO, although the recent increased correlation is not non‐stationary. Consistent with recent studies, the post‐1998 March–May Long Rains decline is strongly associated with decadal variability in the PO. The PVEs in the stable correlations using Pacific Decadal Oscillation and Interdecadal Pacific Oscillation indices range from 25 to 64%, mostly due to low‐frequency variability (>8 years). The results have ramifications for seasonal‐to‐decadal forecasting and can be taken to design modelling studies to gain insights into the physical mechanisms.
Study of polycyclic aromatic hydrocarbons generated from fatty acids by a model system
Authors: Nie Wen , Cai Kezhou , Li Yuzhu , Tu Zehui , Hu Bing , Zhou Cunliu , Chen Conggui , Jiang Shaotong
Published: January 2019

BACKGROUND

The characteristics of carcinogenic polycyclic aromatic hydrocarbons (PAHs) produced from various fatty acids, as important components of fats and oils, at high temperature are still little known. The reason is because the existing data are from experiments conducted in complex food systems. In this study, 12 PAHs produced from nine fatty acids, representing saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs), were investigated in a model system heated at 98, 165 and 240 °C.

RESULTS

SFAs can with difficulty be pyrolyzed to generate PAHs at 98 °C, but small amounts of PAHs were determined in MUFAs (44.97 µg kg−1) and PUFAs (177.73 µg kg−1). When the temperature reached 165 °C, there were totals of 27.59, 142.8 and 449.68 µg kg−1 PAHs assayed in SFAs, MUFAs and PUFAs, respectively. The amounts of PAHs generated from SFAs, MUFAs and PUFAs at 240 °C were higher when compared with those of the 165 °C group (P < 0.05). With an increase of heating temperature, the proportion of PAHs with four to five rings increased. Under the same heating conditions, the concentration of PAHs in fatty acids increased with an increase in the number of double bonds.

CONCLUSIONS

More PAHs, especially carcinogenic ones with four to five rings, will be produced in fatty acids heated at higher temperature. The content of PAHs generated from fatty acids increased with an increase in the number of double bonds. This study will increase the understanding of the production characteristics of PAHs from various fatty acids under heating condition. © 2019 Society of Chemical Industry
Screening and isolation of cyclooxygenase‐2 inhibitors from Trifolium pratense L. via ultrafiltration, enzyme‐immobilized magnetic beads, semi‐preparative high‐performance liquid chromatography and high‐speed counter‐current chromatography
Authors: Hou Wanchao , Li Senlin , Li Sainan , Shi Dongfang , Liu Chunming
Published: January 2019

Nonsteroidal anti‐inflammatory drugs reportedly reduce the risk of developing cancer. One mechanism by which they reduce carcinogenesis involves the inhibition of the activity of cyclooxygenase‐2, an enzyme that is overexpressed in various cancer tissues. Its overexpression increases cell proliferation and inhibits apoptosis. However, selected cyclooxygenase‐2 inhibitors can also act through cyclooxygenase‐independent mechanisms. In this study, using ultrafiltration, enzyme‐immobilized magnetic beads, high‐performance liquid chromatography, and electrospray‐ionization mass spectrometry, several isoflavonoids in Trifolium pratense L. extracts were screened and identified. Semi‐preparative high‐performance liquid chromatography and high‐speed counter‐current chromatography were then applied to separate the active constituents. Using these methods, seven major compounds were identified in Trifolium pratense L. As cyclooxygenase‐2 inhibitors: rothindin, ononin, daidzein, trifoside, pseudobaptigenin, formononetin, and biochanin A, which were then isolated with >92% purity. This is the first report of the presence of potent cyclooxygenase‐2 inhibitors in Trifolium pratense L. extracts. The results of this study demonstrate that the systematic isolation of bioactive components from Trifolium pratense L., by using ultrafiltration, enzyme‐immobilized magnetic beads, semi‐preparative high‐performance liquid chromatography, and high‐speed counter‐current chromatography, represents a feasible and efficient technique that could be extended for the identification and isolation of other enzyme inhibitors.